BENZOPHENONE-3 NOAEL Studies

COSMOS_DB 3 endpoints

Source	Endpoint Type	Value	Unit	Species	Route	Duration	Study Type	Reference
COSMOS_DB	LOAEL	240	mg/kg bw/day	rat	oral	90 day	Subchronic	NTP; NTP Technical report on toxicity studies of 2-Hydroxy-4-methoxybenzophenone Adminstered Topically and in Dosed Feedto F344/N Rats and B6C3F1 Mice
COSMOS_DB	LOAEL	1248	mg/kg bw/day	mouse	oral	90 day	Subchronic	NTP; NTP Technical Report on Toxicity Studies of 2-Hydroxy-4-methoxybenzophenone Adminstered Topically and in Dosed Feedto F344/N Rats and B6C3F1 Mice
COSMOS_DB	NOAEL	544	mg/kg bw/day	mouse	oral	90 day	Subchronic	NTP; NTP Technical Report on Toxicity Studies of 2-Hydroxy-4-methoxybenzophenone Adminstered Topically and in Dosed Feedto F344/N Rats and B6C3F1 Mice

NTP_ICE_acute_oral 3 endpoints

Source	Endpoint Type	Value	Unit	Species	Route	Duration	Study Type	Reference
NTP_ICE_acute_oral	LD50	=7400	mg/kg bw	Rat	oral	acute	Rat Acute Oral Toxicity	NLM ChemIDplus TEST (undated); record_id=acute_oral_2188; row=5592; data_type=In Vivo; mixture=Chemical; chemical_name=2-Hydroxy-4-methoxybenzophenone; preferred_name=2-Hydroxy-4-methoxybenzophenone; dtxsid=DTXSID3022405; url=https://chem.nlm.nih.gov/chemidplus/; url_comptox=https://comptox.epa.gov/dashboard/chemical/details/DTXSID3022405; url_cebs=https://doi.org/10.22427/NTP-DATA-DTXSID3022405; source_file=acute_oral.xlsx
NTP_ICE_acute_oral	LD50	=11600	mg/kg bw	Rat	oral	acute	Rat Acute Oral Toxicity	ECHA ChemProp (undated); record_id=acute_oral_2190; row=5593; data_type=In Vivo; mixture=Chemical; chemical_name=2-Hydroxy-4-methoxybenzophenone; preferred_name=2-Hydroxy-4-methoxybenzophenone; dtxsid=DTXSID3022405; url=https://echa.europa.eu/; url_comptox=https://comptox.epa.gov/dashboard/chemical/details/DTXSID3022405; url_cebs=https://doi.org/10.22427/NTP-DATA-DTXSID3022405; source_file=acute_oral.xlsx
NTP_ICE_acute_oral	LD50	>12800	mg/kg bw	Rat	oral	acute	Rat Acute Oral Toxicity	record_id=acute_oral_2192; row=5594; data_type=In Vivo; mixture=Chemical; chemical_name=2-Hydroxy-4-methoxybenzophenone; preferred_name=2-Hydroxy-4-methoxybenzophenone; dtxsid=DTXSID3022405; url_comptox=https://comptox.epa.gov/dashboard/chemical/details/DTXSID3022405; url_cebs=https://doi.org/10.22427/NTP-DATA-DTXSID3022405; source_file=acute_oral.xlsx

NTP_ICE_adme_parameters 2 endpoints

Source	Endpoint Type	Value	Unit	Species	Route	Duration	Study Type	Reference
NTP_ICE_adme_parameters	Clint	15.7	uL/min/10^6 cells	Human	-	-	Measured; httk, Human Hepatic Intrinsic Clearance	sheet=Data; excel_row=1207; Record_ID=adme_parameters_819; Data_Type=Measured; DTXSID=DTXSID3022405; Assay=httk, Human Hepatic Intrinsic Clearance; Endpoint=Clint; Response=15.7; Response_Unit=ul/min/10^6 cells; Species=Human; Reference=httk2.3.1, Wambaugh 2019; URL=https://cran.r-project.org/web/packages/httk/index.html; URL_CompTox=https://comptox.epa.gov/dashboard/chemical/details/DTXSID3022405; URL_CEBS=https://doi.org/10.22427/NTP-DATA-DTXSID3022405
NTP_ICE_adme_parameters	Fu	0.00952	fraction	Human	-	-	Measured; httk, Human Plasma Fraction Unbound	sheet=Data; excel_row=1206; Record_ID=adme_parameters_819; Data_Type=Measured; DTXSID=DTXSID3022405; Assay=httk, Human Plasma Fraction Unbound; Endpoint=Fu; Response=0.00952; Response_Unit=Unitless Fraction; Species=Human; Reference=httk2.3.1, Wambaugh 2019; URL=https://cran.r-project.org/web/packages/httk/index.html; URL_CompTox=https://comptox.epa.gov/dashboard/chemical/details/DTXSID3022405; URL_CEBS=https://doi.org/10.22427/NTP-DATA-DTXSID3022405

NTP_ICE_endocrine 4 endpoints

Source	Endpoint Type	Value	Unit	Species	Route	Duration	Study Type	Reference
NTP_ICE_endocrine	AC50	26.0389468453684	uM	-	-	-	ERPathway2016; ER Pathway Model, Antagonist	sheet=Integrated_approaches; excel_row=2488; RecordID=ERPathway2016_264; DatasetName=ERPathway2016; DTXSID=DTXSID3022405; Assay=ER Pathway Model, Antagonist; Endpoint=AC50; Response=26.0389468453684; Response_Unit=uM; URL_CompTox=https://comptox.epa.gov/dashboard/chemical/details/DTXSID3022405; URL_CEBS=https://doi.org/10.22427/NTP-DATA-DTXSID3022405
NTP_ICE_endocrine	ACC	13.8887584840494	uM	-	-	-	ERPathway2016; ER Pathway Model, Antagonist	sheet=Integrated_approaches; excel_row=2489; RecordID=ERPathway2016_264; DatasetName=ERPathway2016; DTXSID=DTXSID3022405; Assay=ER Pathway Model, Antagonist; Endpoint=ACC; Response=13.8887584840494; Response_Unit=uM; URL_CompTox=https://comptox.epa.gov/dashboard/chemical/details/DTXSID3022405; URL_CEBS=https://doi.org/10.22427/NTP-DATA-DTXSID3022405
NTP_ICE_endocrine	Model Score	0	unitless	-	-	-	ARPathway2016; AR Pathway Model, Agonist	sheet=Integrated_approaches; excel_row=2484; RecordID=ARPathway2016_777; DatasetName=ARPathway2016; DTXSID=DTXSID3022405; Assay=AR Pathway Model, Agonist; Endpoint=Model Score; Response=0; Response_Unit=Unitless; URL_CompTox=https://comptox.epa.gov/dashboard/chemical/details/DTXSID3022405; URL_CEBS=https://doi.org/10.22427/NTP-DATA-DTXSID3022405
NTP_ICE_endocrine	Model Score	0.0645	unitless	-	-	-	ERPathway2016; ER Pathway Model, Agonist	sheet=Integrated_approaches; excel_row=2490; RecordID=ERPathway2016_264; DatasetName=ERPathway2016; DTXSID=DTXSID3022405; Assay=ER Pathway Model, Agonist; Endpoint=Model Score; Response=0.0645; Response_Unit=Unitless; URL_CompTox=https://comptox.epa.gov/dashboard/chemical/details/DTXSID3022405; URL_CEBS=https://doi.org/10.22427/NTP-DATA-DTXSID3022405

SCCS_vision_codex 308 endpoints

Source	Endpoint Type	Value	Unit	Species	Route	Duration	Study Type	Reference
SCCS_vision_codex	NOAEL	=311	mg/kg bw/day	rat	oral	14d	NOAEL study	{"citation":"Ref.: 30 14-day oral toxicity in mouse (1985-88) Benzophenone-3 was administered in the diet to five B6C3F1 mice per sex and group at concentrations of 0, 3,125","dose":"2,238 mg/kg bw/day: increased liver weights in males and females associated with the presence of cytoplasmic vacuolisation of hepatocytes; increased kidney weights in males 3,868 mg/kg bw/day: reduced feed consumption in males and females; reduced body weight gain in males; increased liver weights in males and females associated with the presenc...","effect":"2,238 mg/kg bw/day: increased liver weights in males and females associated with the presence of cytoplasmic vacuolisation of hepatocytes; increased kidney weights in males 3,868 mg/kg bw/day: reduced feed consumption in males and females; reduced body weight gain in males; increased liver weights in males and females associated with the presence of cytoplasmic vacuolisation of hepatocytes; increased kidney weights in males; focal dilatation of renal tubules in the cortex and/or medulla Study authors' conclusion: NOAEL (14d-oral) = 295/311 mg/kg bw/day for the male/female rat. Ref.: 30 14-day oral toxicity in mouse (1985-88) Benzophenone-3 was administered in the diet to five B6C3F1 mice per sex and group at concentrations of 0, 3,125; 6,250; 12,500; 25,000 and 50,000 ppm for 2 weeks. The dietary test substance preparations were analyzed for stability and proved to be stable in the diet for at least 3 weeks. Clinical examinations covering clinical signs, mortality, body weight and food consumption were performed in all animals","page":12,"pdf":"sccp_o_078.pdf","row_type":"noael_study","study_id":"sccp_o_078_noael_001"}
SCCS_vision_codex	NOAEL	=1050	mg/kg bw/day	rat	oral	14d	repeated dose toxicity	{"citation":"Ref.: 30 B","dose":"y: increased liver weights in males and females associated with the presence of cytoplasmic vacuolisation of hepatocytes 8,648 mg/kg bw/day: increased liver weights in males and females associated with the presence of cytoplasmic vacuolisation of hepatocytes; decreased kidney weight in males 20,796 mg/kg bw/day: reduced body weight gain; increas...","effect":"y: increased liver weights in males and females associated with the presence of cytoplasmic vacuolisation of hepatocytes 8,648 mg/kg bw/day: increased liver weights in males and females associated with the presence of cytoplasmic vacuolisation of hepatocytes; decreased kidney weight in males 20,796 mg/kg bw/day: reduced body weight gain; increased liver weights in males and females associated with the presence of cytoplasmic vacuolisation of hepatocytes; decreased kidney weight in males Study authors' conclusion: NOAEL (14d-oral) = 992/1050 mg/kg bw/day for the male/female mouse. Ref.: 30 B. Subacute dermal administration to rats and mice 14-day dermal toxicity in rat (1985-88) Five F344/N rats per sex and group received Benzophenone-3 at dose levels of 0, 1.25, 2.5, 5.0, 10.0, 20.0 mg/rat in acetone or lotion as vehicle for 5 days per week for 2 weeks. A constant volume of 0.25 ml/rat was applied over a fixed standard area (10%) of the interscapular region. The area was clipped 24 hours prior to initial application and weekl","page":13,"pdf":"sccp_o_078.pdf","row_type":"noael_study","study_id":"sccp_o_078_noael_002"}
SCCS_vision_codex	NOAEL	=140	mg/kg bw/day	rat	oral	14d	NOAEL study	{"citation":"Ref.: 30 28-day dermal toxicity in rat (1985-88) A publication of 1995 describes how 6 male Sprague-Dawley rats per group received Benzophenone-3, formulated in petroleum jelly base, at","dose":"7.0 mg/kg bw/day: no adverse effects noted 13.6 mg/kg bw/day: no adverse effects noted 27.7 mg/kg bw/day: slightly increased liver weights in females 54.9 mg/kg bw/day: slightly increased liver weights in female 110 mg/kg bw/day: slightly increased liver weights in females; slightly increased kidney weights Study authors' conclusion:","effect":"ficed and macroscopically examined, organs were weighed and comprehensive histopathology was performed. The following effects were noted (dietary levels were converted to dosages): 7.0 mg/kg bw/day: no adverse effects noted 13.6 mg/kg bw/day: no adverse effects noted 27.7 mg/kg bw/day: slightly increased liver weights in females 54.9 mg/kg bw/day: slightly increased liver weights in female 110 mg/kg bw/day: slightly increased liver weights in females; slightly increased kidney weights Study authors' conclusion: NOAEL (14d-dermal) = 100/140 mg/kg bw/day for the male/female rat. Ref.: 30 28-day dermal toxicity in rat (1985-88) A publication of 1995 describes how 6 male Sprague-Dawley rats per group received Benzophenone-3, formulated in petroleum jelly base, at dosage levels of 0 and 100 mg/kg bw/day, twice daily for 4 weeks. Clinical examinations covering clinical signs and body weight were performed in all animals. Blood samples for haematology and clinical chemistry were taken prior to the start of treatment and on day 16.","page":13,"pdf":"sccp_o_078.pdf","row_type":"noael_study","study_id":"sccp_o_078_noael_003"}
SCCS_vision_codex	NOAEL	=432	mg/kg bw/day	rat	oral	14d	repeated dose toxicity	{"citation":"Ref.: 30 3","dose":"24.8 mg/kg bw/day: none 48.4 mg/kg bw/day: none 100 mg/kg bw/day: none 196 mg/kg bw/day: increased liver weight 388 mg/kg bw/day: increased liver weight Study authors' conclusion:","effect":"tions covering clinical signs, mortality, body weight and food consumption were performed in all animals. At termination of treatment, all animals were sacrificed and macroscopically examined, organs were weighed and comprehensive histopathology was performed. The following effects were noted (applied doses were converted to dosages): 24.8 mg/kg bw/day: none 48.4 mg/kg bw/day: none 100 mg/kg bw/day: none 196 mg/kg bw/day: increased liver weight 388 mg/kg bw/day: increased liver weight Study authors' conclusion: NOAEL (14d-dermal) = 384/432 mg/kg bw/day for the male/female mouse. Ref.: 30 3.3.5.2 Sub-chronic (90 days) oral / dermal / inhalation toxicity - rat/mouse A. Sub-chronic oral administration to rats and mice 90-day oral toxicity in rat (1) (1972) Benzophenone-3 (source and batch not cited) was examined in 12 male and 12 female rats per sex and group at dosages of approximately 0, 20, 100, 500 and 1,000 mg/kg bw/day for 13 weeks. The animals were observed for clinical findings and body weight and food consumption was","page":14,"pdf":"sccp_o_078.pdf","row_type":"noael_study","study_id":"sccp_o_078_noael_004"}
SCCS_vision_codex	NOAEL	=100	mg/kg bw/day	rat	oral	12 weeks	NOAEL study	{"citation":"Ref.: 44 90-day oral toxicity in rat (2) (1985-1988) Ten F344/N rats per sex and group received Benzophenone-3 in concentrations of 0","dose":"NOEL (90d-oral) = 100 mg/kg bw/day for male and female rats.","effect":"males; anaemia, lymphocytosis and reduced number of granulocytes after 12 weeks in females; decreased absolute weights of the thymus, heart, pituitary gland, lungs, spleen, adrenal glands, and gonads in males and females; decreased relative weights of the pituitary gland, thymus, heart and adrenal glands in males and females; decreased relative weights of the lungs and spleen in females; increased relative thyroid weight in females; degenerative nephritis in kidneys of males and females Study authors' conclusion: NOEL (90d-oral) = 100 mg/kg bw/day for male and female rats. Ref.: 44 90-day oral toxicity in rat (2) (1985-1988) Ten F344/N rats per sex and group received Benzophenone-3 in concentrations of 0; 3,125; 6,250; 12,500; 25,000 and 50,000 ppm in the diet for 13 weeks. The dietary test substance preparations were analyzed for stability and proved to be stable in the diet for at least 3 weeks. Clinical examinations covering clinical signs, mortality, body weight and food consumption were performed in all animals at regula","page":15,"pdf":"sccp_o_078.pdf","row_type":"noael_study","study_id":"sccp_o_078_noael_005"}
SCCS_vision_codex	NOAEL	=393	mg/kg bw/day	rat	oral	90d	NOAEL study	{"citation":"Ref.: 30","dose":"NOAEL (90d-oral) = 429/393 mg/kg bw/day for the male/female rat.","effect":"SCCP/1069/06 OPINION ON BENZOPHENONE-3 16 Study authors' conclusion: NOAEL (90d-oral) = 429/393 mg/kg bw/day for the male/female rat. Ref.: 30","page":16,"pdf":"sccp_o_078.pdf","row_type":"noael_study","study_id":"sccp_o_078_noael_006"}
SCCS_vision_codex	NOAEL	=1425	mg/kg bw/day	rat	oral	90d	repeated dose toxicity	{"citation":"Ref.: 30 B","dose":"y: increased liver weight 2,860 mg/kg bw/day: increased liver weight 6,780 mg/kg bw/day: decreased body weight gain in males and females; increased liver weight; minimal cytoplasmic vacuolisation of hepatocytes 16,238 mg/kg bw/day: decreased body weight gain in males and females; minimal renal lesions in males; increased liver weight; minimal cy...","effect":"y: increased liver weight 2,860 mg/kg bw/day: increased liver weight 6,780 mg/kg bw/day: decreased body weight gain in males and females; increased liver weight; minimal cytoplasmic vacuolisation of hepatocytes 16,238 mg/kg bw/day: decreased body weight gain in males and females; minimal renal lesions in males; increased liver weight; minimal cytoplasmic vacuolisation of hepatocytes; decreased sperm density and increased abnormal sperm in males; increased estrous cycle length in females Study authors' conclusion: NOAEL (90d-oral) = 1068/1425 mg/kg bw/day for the male/female mouse. Ref.: 30 B. Sub-chronic dermal administration to rats and mice 90-day dermal toxicity in rat (1985-88) Ten F344/N rats per sex and groups received Benzophenone-3 preparations at dosage levels of 0, 12.5, 25, 50, 100, 200 mg/kg bw/day in acetone for 5 days per week over a period of 13 weeks. A constant volume of 0.25 ml/rat was applied over a fixed standard area (10%) of the interscapular region. The area was clipped 24 hours prior to initial applic","page":17,"pdf":"sccp_o_078.pdf","row_type":"noael_study","study_id":"sccp_o_078_noael_007"}
SCCS_vision_codex	NOAEL	=200	mg/kg bw/day	rat	dermal	90d	NOAEL study	{"citation":"Ref.: 30 90-day dermal toxicity in mouse Ten B6C3F1 mice per sex and group received Benzophenone-3 preparations at dosage levels of 0, 22","dose":"SCCP/1069/06 OPINION ON BENZOPHENONE-3 18 200 mg/kg bw/day: non-dosage related increase in relative kidney weight in females; decreased reticulocyte count; increased platelet count; increased whole blood cell count produced by lymphocytosis Study authors' conclusion:","effect":"SCCP/1069/06 OPINION ON BENZOPHENONE-3 18 200 mg/kg bw/day: non-dosage related increase in relative kidney weight in females; decreased reticulocyte count; increased platelet count; increased whole blood cell count produced by lymphocytosis Study authors' conclusion: NOAEL (90d-dermal) = 200 mg/kg bw/day for male and female rats. Ref.: 30 90-day dermal toxicity in mouse Ten B6C3F1 mice per sex and group received Benzophenone-3 preparations at dosage levels of 0, 22.8, 45.5, 91, 182, 364 mg/kg bw/day in acetone for 5 days per week over a period of 13 weeks. A constant volume of 0.1 ml was applied over a fixed standard area (10%) of the interscapular region. The area was clipped 24 hours prior to initial application and weekly thereafter. The preparations in acetone were analyzed fo","page":18,"pdf":"sccp_o_078.pdf","row_type":"noael_study","study_id":"sccp_o_078_noael_008"}
SCCS_vision_codex	NOAEL	=364	mg/kg bw/day	rat	oral	90d	repeated dose toxicity	{"citation":"Ref.: 30 3","dose":"Sperm morphology/motility and vaginal cytology examinations were performed at dosage levels of 0, 22.8, 91, 364 mg/kg bw/day.","effect":"ll animals at regular intervals. Sperm morphology/motility and vaginal cytology examinations were performed at dosage levels of 0, 22.8, 91, 364 mg/kg bw/day. At termination of treatment, all animals were sacrificed and macroscopically examined, organs were weighed and comprehensive histopathology was performed. At all dosage levels, a mild increase in relative kidney weight in males, together with a decrease in epididymal sperm density, was noted. No other abnormalities were observed. Study authors' conclusion: NOAEL (90d-dermal) = 364 mg/kg bw/day for male and female mice. Ref.: 30 3.3.5.3 Chronic (> 12 months) toxicity No data. 3.3.5.4 Overall conclusion of the submission authors on repeated dose toxicity The toxicity of Benzophenone-3 after repeated application was comprehensively examined in subacute up to subchronic studies in rats and mice using the oral and dermal application route. The systemic toxicity after repeated oral application was low and effects could mainly be observed at dose levels which were in the ran","page":18,"pdf":"sccp_o_078.pdf","row_type":"noael_study","study_id":"sccp_o_078_noael_009"}
SCCS_vision_codex	NOAEL	=6250	ppm	rat	oral	subchronic	repeated dose toxicity	{"dose":"ly >3000 mg/kg bw/day in rats and >13000 mg/kg bw/day in mice after subchronic oral treatment, an impairment of selective reproductive parameters was noted.","effect":"ly >3000 mg/kg bw/day in rats and >13000 mg/kg bw/day in mice after subchronic oral treatment, an impairment of selective reproductive parameters was noted. However, these are finally assessed in the reproduction section within this dossier (section 3.3.8 Reproductive toxicity). Repeated dermal application of up to 13 weeks in rats and mice did not lead to any reliable substance-related local or systemic findings up to the highest dose level investigated in each case. Finally, the reliable No-Adverse-Effect-Level (NOAEL) for subchronic toxicity after oral treatment was 6250 ppm (429/393 mg/kg bw/day in males/females) in rats and 6250 ppm (1068/1425 mg/kg bw/day in males/females) in mice.","page":18,"pdf":"sccp_o_078.pdf","row_type":"noael_study","study_id":"sccp_o_078_noael_010"}
SCCS_vision_codex	NOAEL	=828	mg/kg bw/day	rat	oral	-	reproductive toxicity	{"citation":"Ref.: 24, 30","dose":"204 mg/kg bw/day: no deviations among the reproductive parameters studied 828 mg/kg bw/day: no deviations among the reproductive parameters studied 3,458 mg/kg bw/day: males: decreased right caudal, testicular and epididymal weights; decreased sperm number per caudal tissue females : prolonged cycle length.","effect":"ssue weight. Observations in the females included vaginal cytology examinations and estrual cyclicity. The following effects were noted (dietary levels were converted to dosages): 204 mg/kg bw/day: no deviations among the reproductive parameters studied 828 mg/kg bw/day: no deviations among the reproductive parameters studied 3,458 mg/kg bw/day: males: decreased right caudal, testicular and epididymal weights; decreased sperm number per caudal tissue females : prolonged cycle length. Study authors' conclusion: NOAEL (reproduction) = 828 mg/kg bw/day for male and female rats. Ref.: 24, 30","page":21,"pdf":"sccp_o_078.pdf","row_type":"noael_study","study_id":"sccp_o_078_noael_012"}
SCCS_vision_codex	NOAEL	=2860	mg/kg bw/day	mouse	oral	-	reproductive toxicity	{"citation":"Ref.: 24, 30 Reproductive Assessment by Continuous Breeding (RACB) in the mouse (1991) The \"Continuous Breeding Protocol\" is a test design used by the US National Toxicology Program","dose":"554 mg/kg bw/day: no deviations among the reproductive parameters studied 2,860 mg/kg bw/day: no deviations among the reproductive parameters studied 16,238 mg/kg bw/day: decreased sperm number per caudal tissue and increased incidence of abnormal sperm in the males Study authors' conclusion:","effect":"d morphology and sperm number per caudal tissue weight. Observations in the females included vaginal cytology examinations and estrual cyclicity. The following effects were noted (dietary levels were converted to dosages): 554 mg/kg bw/day: no deviations among the reproductive parameters studied 2,860 mg/kg bw/day: no deviations among the reproductive parameters studied 16,238 mg/kg bw/day: decreased sperm number per caudal tissue and increased incidence of abnormal sperm in the males Study authors' conclusion: NOAEL (reproduction) = 2,860 mg/kg bw/day for male and female mice. Ref.: 24, 30 Reproductive Assessment by Continuous Breeding (RACB) in the mouse (1991) The \"Continuous Breeding Protocol\" is a test design used by the US National Toxicology Program. It consists of four related tasks (see figure below), which are not all necessarily performed for every compound tested. TASK 4 Offspring assessment F1 generation (Control + 1 dosed group) TASK 3 Determination of affected sex (F0 generation) TASK 4 Offspring assessment F","page":22,"pdf":"sccp_o_078.pdf","row_type":"noael_study","study_id":"sccp_o_078_noael_013"}
SCCS_vision_codex	NOAEL	=9500	mg/kg bw/day	mouse	dermal	20-day	reproductive toxicity	{"citation":"Ref.: 9, 31 B","dose":"5 dams died unexpectedly during the Task 2 20-day period 3,950 mg/kg bw/day: reduced number of pups / litter; reduced dam weights;","effect":"ation, necropsy was performed, organs were weighed and preserved for histopathology (especially reproductive organs). The following effects were noted: 1,850 mg/kg bw/day: 5 dams died unexpectedly during the Task 2 20-day period 3,950 mg/kg bw/day: reduced number of pups / litter; reduced dam weights; 4 dams died unexpectedly during the Task 2 20-day period 9,050mg/kg bw/day: reduced number of pups / litter; reduced dam weights; 9 dams died unexpectedly during the Task 2 20-day period Study authors' conclusion: NOAEL (fertility) = 8600/9500 mg/kg bw/day for male/female mice. Ref.: 9, 31 B. Dermal reproduction toxicity screening tests A short communication published in 1993 describes the assessment of the reproductive toxic potential of Benzophenone-3 in male B6C3F1 mice after a 13-week repeated dermal application of dosages of 0, 20, 100 and 400 mg/kg bw/day. Reproductive organ weights, cauda epididymal sperm concentration, proportion of motile and abnormal sperm and testicular spermatid concentration were determined and tes","page":23,"pdf":"sccp_o_078.pdf","row_type":"noael_study","study_id":"sccp_o_078_noael_014"}
SCCS_vision_codex	NOAEL	=400	mg/kg bw/day	mouse	oral	sub-chronic	repeated dose toxicity	{"citation":"Ref.: 21 Finally, the results of the examinations of sperm morphology/motility and vaginal cytology in the dermal sub-chronic toxicity studies as described under 3","dose":"Since neither any effect on body weight gain nor any abnormalities in the measured reproductive parameters were noted, the study authors conclude that topically applied Benzophenone-3 has no reproductive toxic potential in male B6C3F1 mice at dosages up to 400 mg/kg bw/day.","effect":"0 mg/kg bw/day. Reproductive organ weights, cauda epididymal sperm concentration, proportion of motile and abnormal sperm and testicular spermatid concentration were determined and testicular histology was evaluated. Since neither any effect on body weight gain nor any abnormalities in the measured reproductive parameters were noted, the study authors conclude that topically applied Benzophenone-3 has no reproductive toxic potential in male B6C3F1 mice at dosages up to 400 mg/kg bw/day. Study authors' conclusion: NOAEL (reproduction) = 400 mg/kg bw/day for male and female mice. Ref.: 21 Finally, the results of the examinations of sperm morphology/motility and vaginal cytology in the dermal sub-chronic toxicity studies as described under 3.3.5.2.B, revealed a decrease in epididymal sperm density in the male mice. However, this finding is considered incidental 3 Stability of Benzophenone-3 in the diet : at least 3 weeks","page":23,"pdf":"sccp_o_078.pdf","row_type":"noael_study","study_id":"sccp_o_078_noael_015"}
SCCS_vision_codex	NOAEL	=1900	mg/kg bw/day	rat	oral	developmental	reproductive toxicity	{"dose":"The NOAEL for fertility was the highest investigated dosage level of 8600/9500 mg/kg bw/day in male/female mice.","effect":"a RACB (Reproductive Assessment by Continuous Breeding) study in mice. The NOAEL for fertility was the highest investigated dosage level of 8600/9500 mg/kg bw/day in male/female mice. Within this study the reproductive performance was affected in the form of a slightly lower number of live pups at birth. Signs of developmental toxicity consisted of impaired body weight/body weight gain of the pups. However, in any case these effects were only noted at a dosage level with overt parental toxicity. Consequently, the NOAEL for systemic, reproductive and developmental toxicity was 1800/1900 mg/kg bw/day in males/females. Repeated oral application of Benzophenone-3 for 13 weeks to rats and mice caused only slight effects in selective parameters accompanied with overt systemic toxicity at the highest investigated dosage levels of 3656/3261 mg/kg bw/day in male/female rats and 13937/18539 mg/kg bw/day in male/female mice). In rats, the epididymal sperm count was reduced and a decreased absolute cauda, epididymal and testis weight as a","page":25,"pdf":"sccp_o_078.pdf","row_type":"noael_study","study_id":"sccp_o_078_noael_019"}
SCCS_vision_codex	NOAEL	=200	mg/kg bw/d	rat	oral	subchronic	repeated dose toxicity	{"dose":"In any case, the next lower investigated dose level was a clear NOAEL for the investigated reproductive parameters.","effect":"ecreased absolute cauda, epididymal and testis weight as a consequence of the reduced body weight was noted. In female rats, an increase in the length of the oestrous cycle was noted. In mice, a decrease in the epididymal sperm count and an increase the incidence of abnormal sperm was recorded, while female mice (as in rats) revealed an increase in the length of the oestrous cycle. However, in rats and in mice, the oestrous cyclicity was not affected. In any case, the next lower investigated dose level was a clear NOAEL for the investigated reproductive parameters. After subchronic dermal application for 13 weeks no clear or reliable effect on selective reproduction parameter was noted and therefore, the NOAEL was in each case the highest dose level applied, namely 200 mg/kg bw/d in rats and 364 mg/kg bw/d in mice. Although in mice a decrease in the epididymal sperm count was reported at all investigated dose levels, a relation to treatment is considered as very unlikely since in the oral study the administration of dose levels","page":25,"pdf":"sccp_o_078.pdf","row_type":"noael_study","study_id":"sccp_o_078_noael_020"}
SCCS_vision_codex	NOAEL	=411	mg/kg bw/day	rat	oral	90d	repeated dose toxicity	{"dose":"Therefore, according to the submission, the oral NOAEL corresponds to 411 mg/kg bw/day.","effect":"SCCS-rejected applicant NOAEL: ether with some effects on the identified target organs being the kidney and the liver. These effects were partly associated with changes in clinical chemistry. Very often the most susceptible parameter was the increase in liver weight. The latter, however, without any histopathological correlate, is not considered by the submission authors to reflect an adverse effect per se but should be considered as an adaptive metabolic response which is known to be reversible. Therefore, according to the submission, the oral NOAEL corresponds to 411 mg/kg bw/day. With regard to the results of the dermal repeated dose studies, a dermal NOAEL of 200 mg/kg bw/day is put forward, on the assumption that deviations without dose-response relationship and without correlated histopathological findings (e.g. the decreased reticulocyte count, increased relative kidney weight, increased platelet count and whole blood cell count in the 90d dermal study in rat) should not be taken into account.","page":35,"pdf":"sccp_o_078.pdf","row_type":"noael_study","study_id":"sccp_o_078_noael_023"}
SCCS_vision_codex	NOAEL	=18	-	-	oral	subchronic	repeated dose toxicity	{"effect":"Unlabeled table on page 18: Finally, the reliable No-Adverse-Effect-Level (NOAEL) for subchronic toxicity after oral","page":18,"pdf":"sccp_o_078.pdf","row_type":"noael_study","study_id":"sccp_o_078_noael_036"}
SCCS_vision_codex	NOAEL	=1980	-	-	-	-	NOAEL study	{"effect":"Unlabeled table on page 19: A number of publications (1980-1992) describe the results of Benzophenone-3 studied in","page":19,"pdf":"sccp_o_078.pdf","row_type":"noael_study","study_id":"sccp_o_078_noael_038"}
SCCS_vision_codex	NOAEL	=36	-	-	-	-	NOAEL study	{"effect":"Unlabeled table on page 19: and a title page [36] to a more extensive description of the materials and methods [73].","page":19,"pdf":"sccp_o_078.pdf","row_type":"noael_study","study_id":"sccp_o_078_noael_039"}
SCCS_vision_codex	NOAEL	=9	-	-	-	-	NOAEL study	{"effect":"Unlabeled table on page 19: bacteria both, with and without metabolic activation (S9 mix from the liver of Aroclor 1254-","page":19,"pdf":"sccp_o_078.pdf","row_type":"noael_study","study_id":"sccp_o_078_noael_040"}
SCCS_vision_codex	NOAEL	=10	%	-	-	-	NOAEL study	{"effect":"Unlabeled table on page 19: prepared immediately prior to use and contained 10% S9. The tested Salmonella","page":19,"pdf":"sccp_o_078.pdf","row_type":"noael_study","study_id":"sccp_o_078_noael_041"}
SCCS_vision_codex	NOAEL	=97	-	-	-	-	NOAEL study	{"effect":"Unlabeled table on page 19: typhimurium strains were combinations of TA97, TA98, TA100, TA1535, TA1537 and/or","page":19,"pdf":"sccp_o_078.pdf","row_type":"noael_study","study_id":"sccp_o_078_noael_042"}
SCCS_vision_codex	NOAEL	=1538	-	-	-	-	NOAEL study	{"effect":"Unlabeled table on page 19: TA1538 and were exposed to the test substance at various concentrations of","page":19,"pdf":"sccp_o_078.pdf","row_type":"noael_study","study_id":"sccp_o_078_noael_043"}
SCCS_vision_codex	NOAEL	=-3	-	-	-	-	NOAEL study	{"effect":"Unlabeled table on page 19: Benzophenone-3 with and without S9 mix. Positive controls were included to demonstrate","page":19,"pdf":"sccp_o_078.pdf","row_type":"noael_study","study_id":"sccp_o_078_noael_044"}
SCCS_vision_codex	NOAEL	=73	-	-	-	-	NOAEL study	{"effect":"Unlabeled table on page 19: Bacteriotoxicity was reported [73] to be observed at a varying degree at and above 333","page":19,"pdf":"sccp_o_078.pdf","row_type":"noael_study","study_id":"sccp_o_078_noael_045"}
SCCS_vision_codex	NOAEL	=1000	-	-	-	-	NOAEL study	{"effect":"Unlabeled table on page 19: µg/plate and at 1000 µg/plate in all tested strains (TA98, TA100, TA1535, TA1537). In that","page":19,"pdf":"sccp_o_078.pdf","row_type":"noael_study","study_id":"sccp_o_078_noael_046"}
SCCS_vision_codex	NOAEL	=30	%	-	-	-	NOAEL study	{"effect":"Unlabeled table on page 19: weak mutagenic response using 30% of S9 hamster mix.","page":19,"pdf":"sccp_o_078.pdf","row_type":"noael_study","study_id":"sccp_o_078_noael_048"}
SCCS_vision_codex	NOAEL	=2	-	-	-	-	NOAEL study	{"effect":"Unlabeled table on page 19: the respective controls, the increase in the numbers of revertants was less than 2-fold","page":19,"pdf":"sccp_o_078.pdf","row_type":"noael_study","study_id":"sccp_o_078_noael_050"}
SCCS_vision_codex	NOAEL	=3	-	-	-	-	NOAEL study	{"effect":"Unlabeled table on page 19: the tested concentration range between 3 and 333 µg/plate. All other studies (not including","page":19,"pdf":"sccp_o_078.pdf","row_type":"noael_study","study_id":"sccp_o_078_noael_052"}
SCCS_vision_codex	NOAEL	=8	-	-	-	-	NOAEL study	{"citation":"Ref.: 8, 30, 36, 73","effect":"Unlabeled table on page 19: Ref.: 8, 30, 36, 73","page":19,"pdf":"sccp_o_078.pdf","row_type":"noael_study","study_id":"sccp_o_078_noael_057"}
SCCS_vision_codex	NOAEL	=1992	-	-	-	-	NOAEL study	{"effect":"Unlabeled table on page 19: A US National Toxicology program report (1992) briefly describes the results of cytogenetic","page":19,"pdf":"sccp_o_078.pdf","row_type":"noael_study","study_id":"sccp_o_078_noael_058"}
SCCS_vision_codex	NOAEL	=5	-	-	-	-	NOAEL study	{"dose":"Unlabeled table on page 19: exchanges (effective dose range 5-50µg/ml) and chromosomal aberrations (20-45µg/ml) in","effect":"Unlabeled table on page 19: exchanges (effective dose range 5-50µg/ml) and chromosomal aberrations (20-45µg/ml) in","page":19,"pdf":"sccp_o_078.pdf","row_type":"noael_study","study_id":"sccp_o_078_noael_060"}
SCCS_vision_codex	NOAEL	=1254	-	rat	-	-	NOAEL study	{"effect":"Unlabeled table on page 19: the presence of Aroclor 1254-induced male Sprague Dawley rat liver S9.","page":19,"pdf":"sccp_o_078.pdf","row_type":"noael_study","study_id":"sccp_o_078_noael_061"}
SCCS_vision_codex	NOAEL	=24	-	-	-	prenatal	developmental toxicity	{"effect":"Unlabeled table on page 24: effect and that the NOAEL for maternal and prenatal developmental toxicity is","page":24,"pdf":"sccp_o_078.pdf","row_type":"noael_study","study_id":"sccp_o_078_noael_066"}
SCCS_vision_codex	NOAEL	=1	-	-	-	-	NOAEL study	{"effect":"Unlabeled table on page 24: Date of study: 01-16 November 2004","page":24,"pdf":"sccp_o_078.pdf","row_type":"noael_study","study_id":"sccp_o_078_noael_069"}
SCCS_vision_codex	NOAEL	=67	-	-	-	-	NOAEL study	{"effect":"Unlabeled table on page 24: Guideline/method: Annex V to Dir. 67/548/EEC, Method B.31; OECD Guideline 414","page":24,"pdf":"sccp_o_078.pdf","row_type":"noael_study","study_id":"sccp_o_078_noael_070"}
SCCS_vision_codex	NOAEL	=25	-	-	-	-	NOAEL study	{"effect":"Unlabeled table on page 24: Group size: 25 mated females per dosage group","page":24,"pdf":"sccp_o_078.pdf","row_type":"noael_study","study_id":"sccp_o_078_noael_071"}
SCCS_vision_codex	NOAEL	=99.8	%	-	-	-	NOAEL study	{"effect":"Unlabeled table on page 24: Purity: 99.8% (GC-FID)","page":24,"pdf":"sccp_o_078.pdf","row_type":"noael_study","study_id":"sccp_o_078_noael_073"}
SCCS_vision_codex	NOAEL	=35	-	-	oral	-	NOAEL study	{"effect":"Unlabeled table on page 35: reversible. Therefore, according to the submission, the oral NOAEL corresponds to","page":35,"pdf":"sccp_o_078.pdf","row_type":"noael_study","study_id":"sccp_o_078_noael_080"}
SCCS_vision_codex	NOAEL	=411	mg/kg bw/day	rat	oral	90d	repeated dose toxicity	{"dose":"Therefore, according to the 2005-submission, the oral NOAEL corresponded to 411 mg/kg bw/day.","effect":"SCCS-rejected applicant NOAEL: ether with effects on the identified target organs being the kidney and the liver. These effects were partly associated with changes in clinical chemistry. Very often the most susceptible parameter was the increase in liver weight. The latter, however, without any histopathological correlate, is not considered by the submission authors to reflect an adverse effect per se but should be considered as an adaptive metabolic response which is known to be reversible. Therefore, according to the 2005-submission, the oral NOAEL corresponded to 411 mg/kg bw/day. With regard to the results of the dermal repeated dose studies, a dermal NOAEL of 200 mg/kg bw/day was put forward, on the assumption that deviations without dose-response relationship and without correlated histopathological findings (e.g. the decreased reticulocyte count, increased relative kidney weight, increased platelet count and whole blood cell count in the 90d dermal study in rat) should not be taken into account. 8 A teratogenicity study in rat showed BP-3 to be non-ter","page":6,"pdf":"sccp_o_159.pdf","row_type":"noael_study","study_id":"sccp_o_159_noael_001"}
SCCS_vision_codex	NOAEL	=200	mg/kg bw/day	rat	oral	90d	repeated dose toxicity	{"dose":"Therefore, according to the 2005-submission, the oral NOAEL corresponded to 411 mg/kg bw/day.","effect":"SCCS-rejected applicant NOAEL: ciated with changes in clinical chemistry. Very often the most susceptible parameter was the increase in liver weight. The latter, however, without any histopathological correlate, is not considered by the submission authors to reflect an adverse effect per se but should be considered as an adaptive metabolic response which is known to be reversible. Therefore, according to the 2005-submission, the oral NOAEL corresponded to 411 mg/kg bw/day. With regard to the results of the dermal repeated dose studies, a dermal NOAEL of 200 mg/kg bw/day was put forward, on the assumption that deviations without dose-response relationship and without correlated histopathological findings (e.g. the decreased reticulocyte count, increased relative kidney weight, increased platelet count and whole blood cell count in the 90d dermal study in rat) should not be taken into account. 8 A teratogenicity study in rat showed BP-3 to be non-teratogenic under the conditions of the test. Only at the highest dosage level, which also caused maternal toxicity,","page":6,"pdf":"sccp_o_159.pdf","row_type":"noael_study","study_id":"sccp_o_159_noael_002"}
SCCS_vision_codex	NOAEL	=1.78	mg/kg bw/day	rat	dermal	-	dermal absorption	{"dose":"9.9% [mean (3.1%) + 2 SD (2*3.4%)] Applied dose (sunscreen):","effect":"SCCP/1201/08 Opinion on benzophenone-3 13 3.2.4 Safety evaluation (including calculation of the MoS) BP-3 as a UV-filter in sunscreens up to 6% Dermal absorption (6% formulation): 9.9% [mean (3.1%) + 2 SD (2*3.4%)] Applied dose (sunscreen): 18 g/day Typical human body weight: 60 kg No observed effect level NOAEL (terato-rat): 200 mg/kg bw/day Systemic exposure dose (SED) = (18.103 mg/day * 6/100 * 9.9/100) / 60 kg = 1.78 mg/kg bw/day MoS = NOAEL / SED = 112 BP-3 as a UV-filter at 0.5% to protect cosmetic formulations against sunlight Dermal absorption (2% formulation): 8.0% [mean (4.0%) + 2 SD (2*2.0%)] Applied dose (all cosmetic products): 17.79 g/day Typical human body weight: 60 kg No observed effect level NOAEL (terato-rat): 200 mg/kg bw/day Systemic exposure dose (SED) = (17.79.103 mg/day * 0.5/100 * 8.0/100) / 60 kg = 0.119 mg/kg bw/day MoS = NOAEL / SED = 1686 3.2.5 Discussion A detailed discussion on the general toxicological profile of B","page":13,"pdf":"sccp_o_159.pdf","row_type":"noael_study","study_id":"sccp_o_159_noael_005"}
SCCS_vision_codex	NOAEL	=0.119	mg/kg bw/day	rat	dermal	-	dermal absorption	{"dose":"temic exposure dose (SED) = (18.103 mg/day * 6/100 * 9.9/100) / 60 kg = 1.78 mg/kg bw/day MoS = NOAEL / SED = 112 BP-3 as a UV-filter at 0.5% to protect cosmetic formulations against sunlight Dermal absorption (2% formulation):","effect":"temic exposure dose (SED) = (18.103 mg/day * 6/100 * 9.9/100) / 60 kg = 1.78 mg/kg bw/day MoS = NOAEL / SED = 112 BP-3 as a UV-filter at 0.5% to protect cosmetic formulations against sunlight Dermal absorption (2% formulation): 8.0% [mean (4.0%) + 2 SD (2*2.0%)] Applied dose (all cosmetic products): 17.79 g/day Typical human body weight: 60 kg No observed effect level NOAEL (terato-rat): 200 mg/kg bw/day Systemic exposure dose (SED) = (17.79.103 mg/day * 0.5/100 * 8.0/100) / 60 kg = 0.119 mg/kg bw/day MoS = NOAEL / SED = 1686 3.2.5 Discussion A detailed discussion on the general toxicological profile of BP-3 was given in SCCP/1069/06 and taken over under section 3.1 of the current opinion. The major shortcoming in the dossier was the absence of a sound dermal absorption study, allowing the calculation of the Margin of Safety for the UV-filter. The newly provided in vitro dermal absorption study is considered scientifically acceptable and shows a mean dermal absorption level of 19.3 µg/cm² or 3.1% of the applied dose fo","page":13,"pdf":"sccp_o_159.pdf","row_type":"noael_study","study_id":"sccp_o_159_noael_007"}
SCCS_vision_codex	NOAEL	=6	-	-	oral	-	NOAEL study	{"effect":"Unlabeled table on page 6: reversible. Therefore, according to the 2005-submission, the oral NOAEL corresponded to","page":6,"pdf":"sccp_o_159.pdf","row_type":"noael_study","study_id":"sccp_o_159_noael_009"}
SCCS_vision_codex	NOAEL	=7	-	-	-	developmental	developmental toxicity	{"effect":"Unlabeled table on page 7: skeletal aberrations were noted. The NOAEL-value for maternal and developmental","page":7,"pdf":"sccp_o_159.pdf","row_type":"noael_study","study_id":"sccp_o_159_noael_011"}
SCCS_vision_codex	NOAEL	=56	-	-	-	-	NOAEL study	{"effect":"Unlabeled table on page 7: (cid:56) Toxicokinetic studies indicated that BP-3 was readily biotransformed into its three major","page":7,"pdf":"sccp_o_159.pdf","row_type":"noael_study","study_id":"sccp_o_159_noael_013"}
SCCS_vision_codex	NOAEL	=-3	-	-	-	-	NOAEL study	{"effect":"Unlabeled table on page 7: The SCCP was unable to calculate the Margin of Safety for BP-3 as no scientifically","page":7,"pdf":"sccp_o_159.pdf","row_type":"noael_study","study_id":"sccp_o_159_noael_015"}
SCCS_vision_codex	NOAEL	=3.2	-	-	-	-	NOAEL study	{"effect":"Unlabeled table on page 7: 3.2 DATA INTRODUCED","page":7,"pdf":"sccp_o_159.pdf","row_type":"noael_study","study_id":"sccp_o_159_noael_016"}
SCCS_vision_codex	NOAEL	=13	-	rat	-	-	NOAEL study	{"effect":"Unlabeled table on page 13: The available teratogenicity study in the rat generated a NOAEL-value for maternal and","page":13,"pdf":"sccp_o_159.pdf","row_type":"noael_study","study_id":"sccp_o_159_noael_017"}
SCCS_vision_codex	NOAEL	=19.3	µg/cm	-	dermal	-	dermal absorption	{"dose":"Unlabeled table on page 13: and shows a mean dermal absorption level of 19.3 µg/cm² or 3.1% of the applied dose for a","effect":"Unlabeled table on page 13: and shows a mean dermal absorption level of 19.3 µg/cm² or 3.1% of the applied dose for a","page":13,"pdf":"sccp_o_159.pdf","row_type":"noael_study","study_id":"sccp_o_159_noael_018"}
SCCS_vision_codex	NOAEL	=6	%	-	-	-	NOAEL study	{"effect":"Unlabeled table on page 13: sunscreen (o/w or w/o) containing the maximum requested BP-3 concentration of 6%.","page":13,"pdf":"sccp_o_159.pdf","row_type":"noael_study","study_id":"sccp_o_159_noael_019"}
SCCS_vision_codex	NOAEL	=0.5	%	-	-	-	NOAEL study	{"effect":"Unlabeled table on page 13: protect formulations up to 0.5% in all types of cosmetics), the MoS of BP-3 is above 100.","page":13,"pdf":"sccp_o_159.pdf","row_type":"noael_study","study_id":"sccp_o_159_noael_023"}
SCCS_vision_codex	NOAEL	=411	mg/kg bw/day	rat	oral	90d	repeated dose toxicity	{"dose":"Therefore, according to the 2005- submission, the oral NOAEL corresponded to 411 mg/kg bw/day.","effect":"SCCS-rejected applicant NOAEL: ther with effects on the identified target organs being the kidney and the liver. These effects were partly associated with changes in clinical chemistry. Very often the most susceptible parameter was the increase in liver weight. The latter, however, without any histopathological correlate, is not considered by the submission authors to reflect an adverse effect per se but should be considered as an adaptive metabolic response which is known to be reversible. Therefore, according to the 2005- submission, the oral NOAEL corresponded to 411 mg/kg bw/day. With regard to the results of the dermal repeated dose studies, a dermal NOAEL of 200 mg/kg bw/day was put forward, on the assumption that deviations without dose-response relationship and without correlated histopathological findings (e.g. the decreased reticulocyte count, increased relative kidney weight, increased platelet count and whole blood cell count in the 90d dermal study in rat) should not be taken into account.’ The studies already included in the previous SCCS Opinion","page":25,"pdf":"sccs_o_247.pdf","row_type":"noael_study","study_id":"sccs_o_247_noael_001"}
SCCS_vision_codex	NOAEL	=200	mg/kg bw/day	rat	oral	90d	repeated dose toxicity	{"dose":"Therefore, according to the 2005- submission, the oral NOAEL corresponded to 411 mg/kg bw/day.","effect":"SCCS-rejected applicant NOAEL: iated with changes in clinical chemistry. Very often the most susceptible parameter was the increase in liver weight. The latter, however, without any histopathological correlate, is not considered by the submission authors to reflect an adverse effect per se but should be considered as an adaptive metabolic response which is known to be reversible. Therefore, according to the 2005- submission, the oral NOAEL corresponded to 411 mg/kg bw/day. With regard to the results of the dermal repeated dose studies, a dermal NOAEL of 200 mg/kg bw/day was put forward, on the assumption that deviations without dose-response relationship and without correlated histopathological findings (e.g. the decreased reticulocyte count, increased relative kidney weight, increased platelet count and whole blood cell count in the 90d dermal study in rat) should not be taken into account.’ The studies already included in the previous SCCS Opinion are not detailed in this Opinion; if they provide information on ED effects, they will be described in the secti","page":25,"pdf":"sccs_o_247.pdf","row_type":"noael_study","study_id":"sccs_o_247_noael_002"}
SCCS_vision_codex	NOAEL	=3000	ppm	-	-	developmental	developmental toxicity	{"dose":"However, on PND 4, pup body weights (male, female, and both) in the 10000 ppm exposure groups were statistically significantly decreased (both sexes approximately 5% lower) compared to the control group.","effect":"ere not statistically significantly different across the exposure groups on PND 1. However, on PND 4, pup body weights (male, female, and both) in the 10000 ppm exposure groups were statistically significantly decreased (both sexes approximately 5% lower) compared to the control group. This response was generally observed over subsequent pre-weaning weights, and by PND 21 combined live pup weight at this dose was 8% lower than control. Conclusion from the applicant Under the conditions of this study, the maternal NOAEL is 3000 ppm (206-478 mg/kg bw/day), based on reduced body weight gain during GD 6–9 and lactation day 4–21. The developmental NOEL is considered as 3000 ppm (206-478 mg/kg bw/day) based on impaired postnatal bodyweight performance at 10000 ppm (660-1609 mg/kg bw/day). (National Toxicology Program, 2020) Guidelines/Guidances: NTP Modified One-Generation study design GLP: FDA GLP","page":27,"pdf":"sccs_o_247.pdf","row_type":"noael_study","study_id":"sccs_o_247_noael_005"}
SCCS_vision_codex	NOAEL	=1000	ppm	-	-	-	NOAEL study	{"dose":"Therefore, a decrease in testosterone, which is significant at 3000 ppm (see Fig 7) supports the plausibility of a decrease in spermatocytes numbers.","effect":"reased in the tubules (see Fig 6); it is known that germinal cells are more sensitive than Sertoli cells to apoptosis (and Sertoli cells are less in numbers in the tubules). Moreover, it is well known that testosterone is needed for meiosis (De Gendt et al., 2004). Therefore, a decrease in testosterone, which is significant at 3000 ppm (see Fig 7) supports the plausibility of a decrease in spermatocytes numbers. Due to the effects on the ↓ of spermatocytes, the SCCS considered 3000 ppm as a LOAEL and therefore the NOAEL is 1000 ppm (67.9 mg /kg bw/day). This value will be used by the SCCS as a point of departure (POD) for the MoS calculation (see section 3.5 safety evaluation)","page":39,"pdf":"sccs_o_247.pdf","row_type":"noael_study","study_id":"sccs_o_247_noael_007"}
SCCS_vision_codex	NOAEL	>99	%	mouse	-	5 weeks	NOAEL study	{"dose":"The lowest dose (30 µg/kg/d) was chosen on the basis of equivalence to the EFSA Tolerable Daily Intake (TDI), whereas 212 µg/kg/d for being close to the 95 percentile reported in human biomonitoring studies in pregnant women, and 3000 µg/kg/d for equivalence to the NOAEL used by EFSA as a point of departure (POD) to derive the TDI.","effect":"housed in polysulfone cages with food (which may have contained phytoestrogens) were exposed orally to BP-3 (>99% purity) from Gestational Day (GD) until the day before weaning (Lactational Day 21 or LD21) at 3 doses of BP-3 (30, 212 and 3000 µg/kg/d). The lowest dose (30 µg/kg/d) was chosen on the basis of equivalence to the EFSA Tolerable Daily Intake (TDI), whereas 212 µg/kg/d for being close to the 95 percentile reported in human biomonitoring studies in pregnant women, and 3000 µg/kg/d for equivalence to the NOAEL used by EFSA as a point of departure (POD) to derive the TDI. The authors noted that doses around 10 times higher are needed in rodents to produce equivalent levels in human urine, which means that the highest dose was still environmentally relevant. The study included 2 negative control groups: 1 vehicle group and a second group of nulliparous female mice, which were housed under the same conditions. At 5 weeks post-weaning (once mammary gland involution was complete), mice were killed and mammary glands (the lef","page":40,"pdf":"sccs_o_247.pdf","row_type":"noael_study","study_id":"sccs_o_247_noael_008"}
SCCS_vision_codex	NOAEL	=67.9	mg/kg bw/d	-	oral	-	NOAEL study	{"dose":"The NOAEL of 67.9 mg/kg bw/d has been derived from Nakamura et al.","effect":"al Opinion Opinion on Benzophenone-3 (CAS No 131-57-7, EC No 205-031-5) _________________________________________________________________________________________________________________ 47 whilst there are indications from some studies to suggest that BP-3 may have endocrine effects, it is not conclusive enough at present to enable deriving a new endocrine-related toxicological point of departure for use in safety assessment. 3.5 SAFETY EVALUATION (INCLUDING CALCULATION OF THE MOS) The SCCS has used the lowest NOAEL values among those obtained from different toxicological endpoints for the calculation of MoS (summarised in Annex-1). The NOAEL of 67.9 mg/kg bw/d has been derived from Nakamura et al. (2015) study. Because of the evidence for rapid and almost complete absorption of BP-3 from the oral route, the SCCS has not applied any adjustment for bioavailability to this NOAEL value. Details of the calculation of systemic exposure dose (SED) are presented in the Tables in Annex-2. The calculation of MoS for different product","page":47,"pdf":"sccs_o_247.pdf","row_type":"noael_study","study_id":"sccs_o_247_noael_009"}
SCCS_vision_codex	NOAEL	=6	%	rat	oral	prenatal	developmental toxicity	{"dose":"Details of the calculation of systemic exposure dose (SED) are presented in the Tables in Annex-2.","effect":"et al. (2015) study. Because of the evidence for rapid and almost complete absorption of BP-3 from the oral route, the SCCS has not applied any adjustment for bioavailability to this NOAEL value. Details of the calculation of systemic exposure dose (SED) are presented in the Tables in Annex-2. The calculation of MoS for different product types are given in Table 3 below: Table 3: Calculation of Margin of Safety for different products containing BP-3 Products Conc. Surface Systemic Exposure Dose (SED) mg/kg bw/d NOAEL* MOS Dermal Inhalation Oral Total UV cream 6% whole body 1.782 0 0 1.782 67.9 38 UV aerosolised spray 6% whole body 1.782 0.105 0 1.887 67.9 36 UV pump spray 6% whole body 1.782 0.001053 0 1.783 67.9 38 UV face cream 6% face 0.152 0 0 0.152 67.9 447 UV hand cream 6% hand 0.214 0 0 0.214 67.9 317 Non-UV** 0.50% whole body 0.116 0 0 0.116 67.9 585 Lipstick 6% lips 0.000 0 0.054 0.054 67.9 1257 * derived from prenatal and postnatal developmental study, oral, rat (Nakamura et al., 2015) ** to protect cosmetic formulat","page":47,"pdf":"sccs_o_247.pdf","row_type":"noael_study","study_id":"sccs_o_247_noael_012"}
SCCS_vision_codex	NOAEL	=1625	-	rat	-	-	NOAEL study	{"effect":"SCCS/1625/20 Final Opinion Opinion on Benzophenone-3 (CAS No 131-57-7, EC No 205-031-5) _________________________________________________________________________________________________________________ 48 were 0. 187 µg/ml in females and 0.238 µg/mL in males. Twenty-four hours after the first application, the median BP-3 levels in plasma were 0.047 µg/ml in females and 0.041 µg/ml in males. This clearly shows that the levels of BP-3 had exceeded the concentration measured in rats at the NOAEL. 3.6 DISCUSSION The 2008 SCCP Opinion (SCCP/1201/08) had noted a number of shortcomings in the data provided as part of the dossier assessed in an earlier Opinion (SCCP/1069/06). Despite this, the SCS agrees with the SCCP Opinion (2008) that the submission provides a reasonably well- structured overview of the available test descriptions and publications. Physicochemical properties BP-3is a widely used UV filter in cosmetic products. It is an off-white to light-yellow powder with a melting point of 62°C to 65°","page":48,"pdf":"sccs_o_247.pdf","row_type":"noael_study","study_id":"sccs_o_247_noael_013"}
SCCS_vision_codex	NOAEL	=1000	mg/kg bw/day	rat	oral	Prenatal	developmental toxicity	{"citation":"Ref: 5, 33 in submission dossier OECD 414 GLP Rat Wistar CrI: WI (Han) Oral Gavage in corn oil 0, 40, 200 and 1000 mg/kg bw/day From GD5 to GD 19 observatio ns at GD 20 25 No adverse ef","dose":"Summary of the available in vivo studies on reproduction function and ED effects of BP-3 Number and reference Species Strain Model Routes Dose, Exposure period Group size Outcomes reported NOAEL/ LOAEL derived by the authors SCCS Comments General toxicity Reprotoxicity Teratogenicity ED related effects - 1- Prenatal developmen tal tox study Stud...","effect":"SCCS/1625/20 Final Opinion Opinion on Benzophenone-3 (CAS No 131-57-7, EC No 205-031-5) _________________________________________________________________________________________________________________ 62 Annex - 1: Summary of the available in vivo studies on reproduction function and ED effects of BP-3 Number and reference Species Strain Model Routes Dose, Exposure period Group size Outcomes reported NOAEL/ LOAEL derived by the authors SCCS Comments General toxicity Reprotoxicity Teratogenicity ED related effects - 1- Prenatal developmen tal tox study Study period: 2004. Ref: 5, 33 in submission dossier OECD 414 GLP Rat Wistar CrI: WI (Han) Oral Gavage in corn oil 0, 40, 200 and 1000 mg/kg bw/day From GD5 to GD 19 observatio ns at GD 20 25 No adverse effects in the dams no significant difference in the number of implantation sites/litter, mean resorptions/litt er, % litters with resorptions, number and weights of","page":62,"pdf":"sccs_o_247.pdf","row_type":"noael_study","study_id":"sccs_o_247_noael_018"}
SCCS_vision_codex	NOAEL	=200	mg/kg bw/d	rat	oral	-	developmental toxicity	{"citation":"Ref: 5, 33 in submission dossier OECD 414 GLP Rat Wistar CrI: WI (Han) Oral Gavage in corn oil 0, 40, 200 and 1000 mg/kg bw/day From GD5 to GD 19 observatio ns at GD 20 25 No adverse ef","dose":"WI (Han) Oral Gavage in corn oil 0, 40, 200 and 1000 mg/kg bw/day From GD5 to GD 19 observatio ns at GD 20 25 No adverse effects in the dams no significant difference in the number of implantation sites/litter, mean resorptions/litt er, % litters with resorptions, number and weights of live fetuses, between the control and treated groups No tera...","effect":"study Study period: 2004. Ref: 5, 33 in submission dossier OECD 414 GLP Rat Wistar CrI: WI (Han) Oral Gavage in corn oil 0, 40, 200 and 1000 mg/kg bw/day From GD5 to GD 19 observatio ns at GD 20 25 No adverse effects in the dams no significant difference in the number of implantation sites/litter, mean resorptions/litt er, % litters with resorptions, number and weights of live fetuses, between the control and treated groups No teratogenic effects Minor disturbance ad delay of ossification at 1000 mg/kg bw/day NOAEL mat. = 200 mg/kg bw/d NOAEL dev. = 200 mg/kg bw/d This study has been used in the previous SCCS opinion as the key study for calculation of the MOS. - 2 - Nakamura et al. 2015 Birth Defects Res 104: 35- 51 Study period: Rat Sprague- Dawley Food , 0, 1000, 3000, 10 000, 25 000, 50 000 ppm, i.e. around 67.9, 207.1, 670.8, 1798.3, 7-8 ↓ body weights of dams at 50 000 ppm at GD 10, 15 and 20; and at 25 000 ppm at GD15 ↓ organ (liver, kidney) weights (absolute no significant difference in the number of implantation si","page":62,"pdf":"sccs_o_247.pdf","row_type":"noael_study","study_id":"sccs_o_247_noael_019"}
SCCS_vision_codex	NOAEL	=0	ppm	-	-	-	reproductive toxicity	{"dose":"i.e. around 67.9, 207.1, 670.8, 1798.3, 7-8 ↓ body weights of dams at 50 000 ppm at GD 10, 15 and 20; and at 25 000 ppm at GD15 ↓ organ (liver, kidney) weights (absolute no significant difference in the number of implantation sites/litter, mean resorptions/litt er, % litters with resorptions, number and weights of live One foetus with hydrocepha...","effect":"i.e. around 67.9, 207.1, 670.8, 1798.3, 7-8 ↓ body weights of dams at 50 000 ppm at GD 10, 15 and 20; and at 25 000 ppm at GD15 ↓ organ (liver, kidney) weights (absolute no significant difference in the number of implantation sites/litter, mean resorptions/litt er, % litters with resorptions, number and weights of live One foetus with hydrocephaly at 50 000 ppm but no other malformations observed In male offspring at PND23: ↓ AGD in male at 50 000 ppm ↓ spermatocytes per seminiferous tubules at 3000 ppm and higher NOAEL : 3 000 ppm (670 mg/kg bw/day LOAEL : 10 000 ppm (1798 mg/kg/d) It would have been useful to have measured foetal testosterone as it is known that a decrease during specific windows of sensitivity in male foetuses mat impaired the development of reproductive","page":62,"pdf":"sccs_o_247.pdf","row_type":"noael_study","study_id":"sccs_o_247_noael_021"}
SCCS_vision_codex	NOAEL	=242	mg/kg bw/d	rat	oral	-	developmental toxicity	{"dose":"2012 (final report in 2015) Equivalent to OECD 414 GLP Rat Sprague- Dawley Oral Food 0, 3000, 10 000 and 30 000, ppm, i.e. around 242, 725 and 3689 mg/kg/ bw/day From GD 5 to GD 15 Observatio n at GD 15 25 .↓ body weights at 10 000 and 30 000 ppm and ↑ food consumption at 30 000 ppm modifications of blood biochemical factors at 30 000 ppm No eff...","effect":"SCCS-rejected applicant NOAEL: y) - 3 - Submission Ref 11 Study period: 2012 (final report in 2015) Equivalent to OECD 414 GLP Rat Sprague- Dawley Oral Food 0, 3000, 10 000 and 30 000, ppm, i.e. around 242, 725 and 3689 mg/kg/ bw/day From GD 5 to GD 15 Observatio n at GD 15 25 .↓ body weights at 10 000 and 30 000 ppm and ↑ food consumption at 30 000 ppm modifications of blood biochemical factors at 30 000 ppm No effects on foetuses, litters No teratogenic effects observed excepted increased skeletal variations not considered treatment related NOAEL mat. = 242 mg/kg bw/d NOAEL dev. = 3689 mg/kg bw/d SCCS agrees with the authors conclusion.","page":63,"pdf":"sccs_o_247.pdf","row_type":"noael_study","study_id":"sccs_o_247_noael_023"}
SCCS_vision_codex	NOAEL	=411	mg/kg/ day	rat	oral	39 days	NOAEL study	{"dose":"om GD6 during 39 days for F0 and then during 105 weeks for F1 Sacrifice at 14 weeks for 10 F1 rats ( m and f) at 0 and 10 000 ppm course of the study ↑ incidence of pigment in bone marrow at 10 000 ppm in m and f ↑ incidence of pigment in spleen at 10 000 ppm in m and f ↑ incidence of syncytial alteration in the liver of males at all doses ↑ inc...","effect":"om GD6 during 39 days for F0 and then during 105 weeks for F1 Sacrifice at 14 weeks for 10 F1 rats ( m and f) at 0 and 10 000 ppm course of the study ↑ incidence of pigment in bone marrow at 10 000 ppm in m and f ↑ incidence of pigment in spleen at 10 000 ppm in m and f ↑ incidence of syncytial alteration in the liver of males at all doses ↑ incidence of renal alterations at 3000 and 10 000 ppm in males ↑ incidence of osseous metaplasia in females at 10 000 ppm - 6 - Rats Oral Food 0, 3125,625,1 in males: NOAEL = 411 mg/kg/ day","page":65,"pdf":"sccs_o_247.pdf","row_type":"noael_study","study_id":"sccs_o_247_noael_028"}
SCCS_vision_codex	NOAEL	=100	mg/kg bw/day	rat	oral	Sub-chronic	repeated dose toxicity	{"dose":"at 3458 mg/kg bw/day In females: ↑ estrous cycle length in female rats at 3458 mg/kg bw/day based on effects in the kidney - 7 - Ref 7, 16, 33 in submission dossier Sub-chronic toxicity study OECD 408 Non GLP Rats Oral Food 0, 0, 0.02, 0.1, 0.5 and 1% in the diet ie ± 0, 20, 100, 500 and 1000 mg/kg bw/day 13 weeks In males and females: ↓ in abso...","effect":"at 3458 mg/kg bw/day In females: ↑ estrous cycle length in female rats at 3458 mg/kg bw/day based on effects in the kidney - 7 - Ref 7, 16, 33 in submission dossier Sub-chronic toxicity study OECD 408 Non GLP Rats Oral Food 0, 0, 0.02, 0.1, 0.5 and 1% in the diet ie ± 0, 20, 100, 500 and 1000 mg/kg bw/day 13 weeks In males and females: ↓ in absolute weights of adrenal gland, pituitary gland and gonads at 1000 mg/kg bw/day ↑ in relative thyroid and pituitary and adrenal weights at 500 and 1000 mg/kg bw/day NOAEL = 100 mg/kg bw/day","page":66,"pdf":"sccs_o_247.pdf","row_type":"noael_study","study_id":"sccs_o_247_noael_029"}
SCCS_vision_codex	NOAEL	=1246	mg/kg bw /day	rat	oral	Sub-chronic	repeated dose toxicity	{"dose":"___________________________________________________________________________________________________ 67 - 8 - Ref 5, 7, 33 in submission dossier Sub-chronic toxicity study OECD 408 GLP Mice Oral Food 0, 3125,6250, 12500, 25000 and 50000 ppm , ie ± 0, 554, 1246, 2860, 6780 and 16238 mg/kg bw/day 13 weeks No effects on reproductive parameters at 67...","effect":"___________________________________________________________________________________________________ 67 - 8 - Ref 5, 7, 33 in submission dossier Sub-chronic toxicity study OECD 408 GLP Mice Oral Food 0, 3125,6250, 12500, 25000 and 50000 ppm , ie ± 0, 554, 1246, 2860, 6780 and 16238 mg/kg bw/day 13 weeks No effects on reproductive parameters at 6780 mg/kg bw/day or below Males: ↓ in sperm density and ↑ in abnormal sperm morphology at 16238 mg/kg bw/day Females: ↑ in estrous cycles length at 16238 mg/kg bw/day NOAEL = 1246 mg/kg bw /day based on systemic effects -9- Ref 21 Sub-chronic toxicity study GLP Rats 0 and 10000 ppm ie ± 585/632 mg/kg bw/day in males and females Estrogen- responsive genes showed no change in response to BP- 3 in transcriptome analysis -10- Ref 5, 7, 33 in submission dossier Sub-chronic toxicity study ± OECD 411 GLP Rats Dermal 0, 12.5, 25, 50, 100 and 200 mg/kg bw/day 13 weeks No effects on reproductive parameters NOAEL = 200 mg/kg bw/day -11- Mice Dermal 0, 22.8, 45.5, 91, ↓ in epi","page":67,"pdf":"sccs_o_247.pdf","row_type":"noael_study","study_id":"sccs_o_247_noael_030"}
SCCS_vision_codex	NOAEL	=364	mg/kg bw/day	rat	dermal	Sub-chronic	repeated dose toxicity	{"dose":"based on systemic effects -9- Ref 21 Sub-chronic toxicity study GLP Rats 0 and 10000 ppm ie ± 585/632 mg/kg bw/day in males and females Estrogen- responsive genes showed no change in response to BP- 3 in transcriptome analysis -10- Ref 5, 7, 33 in submission dossier Sub-chronic toxicity study ± OECD 411 GLP Rats Dermal 0, 12.5, 25, 50, 100 and 2...","effect":"based on systemic effects -9- Ref 21 Sub-chronic toxicity study GLP Rats 0 and 10000 ppm ie ± 585/632 mg/kg bw/day in males and females Estrogen- responsive genes showed no change in response to BP- 3 in transcriptome analysis -10- Ref 5, 7, 33 in submission dossier Sub-chronic toxicity study ± OECD 411 GLP Rats Dermal 0, 12.5, 25, 50, 100 and 200 mg/kg bw/day 13 weeks No effects on reproductive parameters NOAEL = 200 mg/kg bw/day -11- Mice Dermal 0, 22.8, 45.5, 91, ↓ in epididymal sperm density NOAEL = 364 mg/kg bw/day In view of the effects on sperm","page":67,"pdf":"sccs_o_247.pdf","row_type":"noael_study","study_id":"sccs_o_247_noael_032"}
SCCS_vision_codex	NOAEL	=3	-	-	-	-	NOAEL study	{"dose":"Products | Conc. | Surface | Systemic Exposure Dose (SED) mg/kg bw/d | NOAEL* | MOS","effect":"Table 3: Calculation of Margin of Safety for different products containing BP-3: Products | Conc. | Surface | Systemic Exposure Dose (SED) mg/kg bw/d | NOAEL* | MOS","page":47,"pdf":"sccs_o_247.pdf","row_type":"noael_study","study_id":"sccs_o_247_noael_033"}
SCCS_vision_codex	NOAEL	=0.5	%	-	-	-	NOAEL study	{"effect":"Table 3: Calculation of Margin of Safety for different products containing BP-3: Non-UV** | 0.50% | whole body | 0.116 | 0 | 0 | 0.116 | 67.9 | 585","page":47,"pdf":"sccs_o_247.pdf","row_type":"noael_study","study_id":"sccs_o_247_noael_039"}
SCCS_vision_codex	NOAEL	=62	-	-	-	-	NOAEL study	{"dose":"Number and reference | Species Strain Model | Routes | Dose, Exposure period | Group size | Outcomes reported | NOAEL/ LOAEL derived by the authors | SCCS Comments","effect":"Unlabeled table on page 62: Number and reference | Species Strain Model | Routes | Dose, Exposure period | Group size | Outcomes reported | NOAEL/ LOAEL derived by the authors | SCCS Comments","page":62,"pdf":"sccs_o_247.pdf","row_type":"noael_study","study_id":"sccs_o_247_noael_041"}
SCCS_vision_codex	NOAEL	=3448.2	mg/kg/day	-	-	-	NOAEL study	{"dose":"Unlabeled table on page 63: and 3448.2 mg/kg/day . from GD6 to PND 23 Observatio n on PND1 and PND 23 | and relative) in female and male offspring and blood biochemical factors in the high dose (≥10,000 ppm) groups | fetuses, or sex ratios between the control and treated groups; ↑ ovaries and uterine weights (absolute and relative) at 1000 ppm b...","effect":"Unlabeled table on page 63: and 3448.2 mg/kg/day . from GD6 to PND 23 Observatio n on PND1 and PND 23 | and relative) in female and male offspring and blood biochemical factors in the high dose (≥10,000 ppm) groups | fetuses, or sex ratios between the control and treated groups; ↑ ovaries and uterine weights (absolute and relative) at 1000 ppm but not at higher doses | doses (dose related) ↑ apoptic cells in seminiferous tubules at 10 000 ppm and above (not dose related) Limited ↓ testo level at 3000 and 25 000 ppm In female offspring at PND23 Delayed follicular development at 10 000 and 50 000 ppm | system (↓ AGD, ↓ spermatocytes production and/or quality…) Due to the effects on the ↓ of spermatocyte which may be due to an ED effects of BP-3 SCCS considered 3000 ppm as a LOAEL and therefore the NOAEL should be 1000 ppm ( 68 mg /kg bw/day)","page":63,"pdf":"sccs_o_247.pdf","row_type":"noael_study","study_id":"sccs_o_247_noael_045"}
SCCS_vision_codex	NOAEL	=3689	mg/kg	rat	oral	-	developmental toxicity	{"dose":"2012 (final report in 2015) Equivalent to OECD 414 GLP | Rat Sprague- Dawley | Oral Food | 0, 3000, 10 000 and 30 000, ppm, i.e. around 242, 725 and 3689 mg/kg/ bw/day From GD 5 to GD 15 Observatio n at GD 15 | 25 | .↓ body weights at 10 000 and 30 000 ppm and ↑ food consumption at 30 000 ppm modifications of blood biochemical factors at 30 000...","effect":"SCCS-rejected applicant NOAEL: Unlabeled table on page 63: - 3 - Submission Ref 11 Study period: 2012 (final report in 2015) Equivalent to OECD 414 GLP | Rat Sprague- Dawley | Oral Food | 0, 3000, 10 000 and 30 000, ppm, i.e. around 242, 725 and 3689 mg/kg/ bw/day From GD 5 to GD 15 Observatio n at GD 15 | 25 | .↓ body weights at 10 000 and 30 000 ppm and ↑ food consumption at 30 000 ppm modifications of blood biochemical factors at 30 000 ppm | No effects on foetuses, litters | No teratogenic effects observed excepted increased skeletal variations not considered treatment related | NOAEL mat. = 242 mg/kg bw/d NOAEL dev. = 3689 mg/kg bw/d | SCCS agrees with the authors conclusion.","page":63,"pdf":"sccs_o_247.pdf","row_type":"noael_study","study_id":"sccs_o_247_noael_046"}
SCCS_vision_codex	NOAEL	=660	mg/kg	rat	oral	105 weeks	developmental toxicity	{"dose":"2010-2012 (final report in 2020) Ref 21 in submission dossier GLP | Rat Sprague- Dawley | Oral Food | 0,1000,300 0and 10 000, ppm, i.e. ± 70, 206 and 660 mg/kg/ bw/day during gestation and 157, 478 and 1609 mg/kg bw/day during lactation . from GD6 until PND 21 for F0 and then during 105 weeks for F1 observatio n at PND1, 4, 7 , 14 and 21 | 35-42...","effect":"Unlabeled table on page 64: - 4 - NTP modified 1- gen study equivalent to perinatal developmen tal tox study Study period : 2010-2012 (final report in 2020) Ref 21 in submission dossier GLP | Rat Sprague- Dawley | Oral Food | 0,1000,300 0and 10 000, ppm, i.e. ± 70, 206 and 660 mg/kg/ bw/day during gestation and 157, 478 and 1609 mg/kg bw/day during lactation . from GD6 until PND 21 for F0 and then during 105 weeks for F1 observatio n at PND1, 4, 7 , 14 and 21 | 35-42 femal es for F0 and 50-60 for F1 (m and f) | At 10 000 ppm: ↓ body weights gain in F0 at GD6- 9 and lactation day 4-21 At 3000 ppm: ↓ body weights gain in F0 at GD 18 -21 ↓ body weights of F1 m and f at 10 000 ppm over the course of the study and at 3000 ppm in f at week 77 | No effects on number of pups, litter size, sex distribution, In female F1: ↑ stromal polyp and endometrium hyperplasia ppm in the uterus at 3000 In male F1: ↑ fibirnoid necrosis of the arterioles at 10 000 ppm at the end of the 2 years | No teratogenic effects except at the highest dose: skeletal aberrations in the presence of maternal toxicity |...","page":64,"pdf":"sccs_o_247.pdf","row_type":"noael_study","study_id":"sccs_o_247_noael_048"}
SCCS_vision_codex	NOAEL	=1	%	rat	oral	Sub-chronic	repeated dose toxicity	{"dose":"Unlabeled table on page 66: - 7 - Ref 7, 16, 33 in submission dossier Sub-chronic toxicity study OECD 408 Non GLP | Rats | Oral Food | 0, 0, 0.02, 0.1, 0.5 and 1% in the diet ie ± 0, 20, 100, 500 and 1000 mg/kg bw/day 13 weeks | In males and females: ↓ in absolute weights of adrenal gland, pituitary gland and gonads at 1000 mg/kg bw/day ↑ in rel...","effect":"Unlabeled table on page 66: - 7 - Ref 7, 16, 33 in submission dossier Sub-chronic toxicity study OECD 408 Non GLP | Rats | Oral Food | 0, 0, 0.02, 0.1, 0.5 and 1% in the diet ie ± 0, 20, 100, 500 and 1000 mg/kg bw/day 13 weeks | In males and females: ↓ in absolute weights of adrenal gland, pituitary gland and gonads at 1000 mg/kg bw/day ↑ in relative thyroid and pituitary and adrenal weights at 500 and 1000 mg/kg bw/day | NOAEL = 100 mg/kg bw/day","page":66,"pdf":"sccs_o_247.pdf","row_type":"noael_study","study_id":"sccs_o_247_noael_050"}
SCCS_vision_codex	NOAEL	=50000	ppm	mouse	oral	Sub-chronic	repeated dose toxicity	{"dose":"Unlabeled table on page 67: - 8 - Ref 5, 7, 33 in submission dossier Sub-chronic toxicity study OECD 408 GLP | Mice | Oral Food | 0, 3125,6250, 12500, 25000 and 50000 ppm , ie ± 0, 554, 1246, 2860, 6780 and 16238 mg/kg bw/day 13 weeks | No effects on reproductive parameters at 6780 mg/kg bw/day or below | Males: ↓ in sperm density and ↑ in abnor...","effect":"Unlabeled table on page 67: - 8 - Ref 5, 7, 33 in submission dossier Sub-chronic toxicity study OECD 408 GLP | Mice | Oral Food | 0, 3125,6250, 12500, 25000 and 50000 ppm , ie ± 0, 554, 1246, 2860, 6780 and 16238 mg/kg bw/day 13 weeks | No effects on reproductive parameters at 6780 mg/kg bw/day or below | Males: ↓ in sperm density and ↑ in abnormal sperm morphology at 16238 mg/kg bw/day Females: ↑ in estrous cycles length at 16238 mg/kg bw/day | NOAEL = 1246 mg/kg bw /day based on systemic effects","page":67,"pdf":"sccs_o_247.pdf","row_type":"noael_study","study_id":"sccs_o_247_noael_052"}
SCCS_vision_codex	NOAEL	=311	mg/kg bw/day	rat	oral	14d	NOAEL study	{"citation":"Ref.: 30 14-day oral toxicity in mouse (1985-88) Benzophenone-3 was administered in the diet to five B6C3F1 mice per sex and group at concentrations of 0, 3,125","dose":"2,238 mg/kg bw/day: increased liver weights in males and females associated with the presence of cytoplasmic vacuolisation of hepatocytes; increased kidney weights in males 3,868 mg/kg bw/day: reduced feed consumption in males and females; reduced body weight gain in males; increased liver weights in males and females associated with the presenc...","effect":"2,238 mg/kg bw/day: increased liver weights in males and females associated with the presence of cytoplasmic vacuolisation of hepatocytes; increased kidney weights in males 3,868 mg/kg bw/day: reduced feed consumption in males and females; reduced body weight gain in males; increased liver weights in males and females associated with the presence of cytoplasmic vacuolisation of hepatocytes; increased kidney weights in males; focal dilatation of renal tubules in the cortex and/or medulla Study authors' conclusion: NOAEL (14d-oral) = 295/311 mg/kg bw/day for the male/female rat. Ref.: 30 14-day oral toxicity in mouse (1985-88) Benzophenone-3 was administered in the diet to five B6C3F1 mice per sex and group at concentrations of 0, 3,125; 6,250; 12,500; 25,000 and 50,000 ppm for 2 weeks. The dietary test substance preparations were analyzed for stability and proved to be stable in the diet for at least 3 weeks. Clinical examinations covering clinical signs, mortality, body weight and food consumption were performed in all animals","page":12,"pdf":"sccp_o_078.pdf","row_type":"noael_study","study_id":"sccp_o_078_noael_001"}
SCCS_vision_codex	NOAEL	=1050	mg/kg bw/day	rat	oral	14d	repeated dose toxicity	{"citation":"Ref.: 30 B","dose":"y: increased liver weights in males and females associated with the presence of cytoplasmic vacuolisation of hepatocytes 8,648 mg/kg bw/day: increased liver weights in males and females associated with the presence of cytoplasmic vacuolisation of hepatocytes; decreased kidney weight in males 20,796 mg/kg bw/day: reduced body weight gain; increas...","effect":"y: increased liver weights in males and females associated with the presence of cytoplasmic vacuolisation of hepatocytes 8,648 mg/kg bw/day: increased liver weights in males and females associated with the presence of cytoplasmic vacuolisation of hepatocytes; decreased kidney weight in males 20,796 mg/kg bw/day: reduced body weight gain; increased liver weights in males and females associated with the presence of cytoplasmic vacuolisation of hepatocytes; decreased kidney weight in males Study authors' conclusion: NOAEL (14d-oral) = 992/1050 mg/kg bw/day for the male/female mouse. Ref.: 30 B. Subacute dermal administration to rats and mice 14-day dermal toxicity in rat (1985-88) Five F344/N rats per sex and group received Benzophenone-3 at dose levels of 0, 1.25, 2.5, 5.0, 10.0, 20.0 mg/rat in acetone or lotion as vehicle for 5 days per week for 2 weeks. A constant volume of 0.25 ml/rat was applied over a fixed standard area (10%) of the interscapular region. The area was clipped 24 hours prior to initial application and weekl","page":13,"pdf":"sccp_o_078.pdf","row_type":"noael_study","study_id":"sccp_o_078_noael_002"}
SCCS_vision_codex	NOAEL	=140	mg/kg bw/day	rat	oral	14d	NOAEL study	{"citation":"Ref.: 30 28-day dermal toxicity in rat (1985-88) A publication of 1995 describes how 6 male Sprague-Dawley rats per group received Benzophenone-3, formulated in petroleum jelly base, at","dose":"7.0 mg/kg bw/day: no adverse effects noted 13.6 mg/kg bw/day: no adverse effects noted 27.7 mg/kg bw/day: slightly increased liver weights in females 54.9 mg/kg bw/day: slightly increased liver weights in female 110 mg/kg bw/day: slightly increased liver weights in females; slightly increased kidney weights Study authors' conclusion:","effect":"ficed and macroscopically examined, organs were weighed and comprehensive histopathology was performed. The following effects were noted (dietary levels were converted to dosages): 7.0 mg/kg bw/day: no adverse effects noted 13.6 mg/kg bw/day: no adverse effects noted 27.7 mg/kg bw/day: slightly increased liver weights in females 54.9 mg/kg bw/day: slightly increased liver weights in female 110 mg/kg bw/day: slightly increased liver weights in females; slightly increased kidney weights Study authors' conclusion: NOAEL (14d-dermal) = 100/140 mg/kg bw/day for the male/female rat. Ref.: 30 28-day dermal toxicity in rat (1985-88) A publication of 1995 describes how 6 male Sprague-Dawley rats per group received Benzophenone-3, formulated in petroleum jelly base, at dosage levels of 0 and 100 mg/kg bw/day, twice daily for 4 weeks. Clinical examinations covering clinical signs and body weight were performed in all animals. Blood samples for haematology and clinical chemistry were taken prior to the start of treatment and on day 16.","page":13,"pdf":"sccp_o_078.pdf","row_type":"noael_study","study_id":"sccp_o_078_noael_003"}
SCCS_vision_codex	NOAEL	=432	mg/kg bw/day	rat	oral	14d	repeated dose toxicity	{"citation":"Ref.: 30 3","dose":"24.8 mg/kg bw/day: none 48.4 mg/kg bw/day: none 100 mg/kg bw/day: none 196 mg/kg bw/day: increased liver weight 388 mg/kg bw/day: increased liver weight Study authors' conclusion:","effect":"tions covering clinical signs, mortality, body weight and food consumption were performed in all animals. At termination of treatment, all animals were sacrificed and macroscopically examined, organs were weighed and comprehensive histopathology was performed. The following effects were noted (applied doses were converted to dosages): 24.8 mg/kg bw/day: none 48.4 mg/kg bw/day: none 100 mg/kg bw/day: none 196 mg/kg bw/day: increased liver weight 388 mg/kg bw/day: increased liver weight Study authors' conclusion: NOAEL (14d-dermal) = 384/432 mg/kg bw/day for the male/female mouse. Ref.: 30 3.3.5.2 Sub-chronic (90 days) oral / dermal / inhalation toxicity - rat/mouse A. Sub-chronic oral administration to rats and mice 90-day oral toxicity in rat (1) (1972) Benzophenone-3 (source and batch not cited) was examined in 12 male and 12 female rats per sex and group at dosages of approximately 0, 20, 100, 500 and 1,000 mg/kg bw/day for 13 weeks. The animals were observed for clinical findings and body weight and food consumption was","page":14,"pdf":"sccp_o_078.pdf","row_type":"noael_study","study_id":"sccp_o_078_noael_004"}
SCCS_vision_codex	NOAEL	=100	mg/kg bw/day	rat	oral	12 weeks	NOAEL study	{"citation":"Ref.: 44 90-day oral toxicity in rat (2) (1985-1988) Ten F344/N rats per sex and group received Benzophenone-3 in concentrations of 0","dose":"NOEL (90d-oral) = 100 mg/kg bw/day for male and female rats.","effect":"males; anaemia, lymphocytosis and reduced number of granulocytes after 12 weeks in females; decreased absolute weights of the thymus, heart, pituitary gland, lungs, spleen, adrenal glands, and gonads in males and females; decreased relative weights of the pituitary gland, thymus, heart and adrenal glands in males and females; decreased relative weights of the lungs and spleen in females; increased relative thyroid weight in females; degenerative nephritis in kidneys of males and females Study authors' conclusion: NOEL (90d-oral) = 100 mg/kg bw/day for male and female rats. Ref.: 44 90-day oral toxicity in rat (2) (1985-1988) Ten F344/N rats per sex and group received Benzophenone-3 in concentrations of 0; 3,125; 6,250; 12,500; 25,000 and 50,000 ppm in the diet for 13 weeks. The dietary test substance preparations were analyzed for stability and proved to be stable in the diet for at least 3 weeks. Clinical examinations covering clinical signs, mortality, body weight and food consumption were performed in all animals at regula","page":15,"pdf":"sccp_o_078.pdf","row_type":"noael_study","study_id":"sccp_o_078_noael_005"}
SCCS_vision_codex	NOAEL	=393	mg/kg bw/day	rat	oral	90d	NOAEL study	{"citation":"Ref.: 30","dose":"NOAEL (90d-oral) = 429/393 mg/kg bw/day for the male/female rat.","effect":"SCCP/1069/06 OPINION ON BENZOPHENONE-3 16 Study authors' conclusion: NOAEL (90d-oral) = 429/393 mg/kg bw/day for the male/female rat. Ref.: 30","page":16,"pdf":"sccp_o_078.pdf","row_type":"noael_study","study_id":"sccp_o_078_noael_006"}
SCCS_vision_codex	NOAEL	=1425	mg/kg bw/day	rat	oral	90d	repeated dose toxicity	{"citation":"Ref.: 30 B","dose":"y: increased liver weight 2,860 mg/kg bw/day: increased liver weight 6,780 mg/kg bw/day: decreased body weight gain in males and females; increased liver weight; minimal cytoplasmic vacuolisation of hepatocytes 16,238 mg/kg bw/day: decreased body weight gain in males and females; minimal renal lesions in males; increased liver weight; minimal cy...","effect":"y: increased liver weight 2,860 mg/kg bw/day: increased liver weight 6,780 mg/kg bw/day: decreased body weight gain in males and females; increased liver weight; minimal cytoplasmic vacuolisation of hepatocytes 16,238 mg/kg bw/day: decreased body weight gain in males and females; minimal renal lesions in males; increased liver weight; minimal cytoplasmic vacuolisation of hepatocytes; decreased sperm density and increased abnormal sperm in males; increased estrous cycle length in females Study authors' conclusion: NOAEL (90d-oral) = 1068/1425 mg/kg bw/day for the male/female mouse. Ref.: 30 B. Sub-chronic dermal administration to rats and mice 90-day dermal toxicity in rat (1985-88) Ten F344/N rats per sex and groups received Benzophenone-3 preparations at dosage levels of 0, 12.5, 25, 50, 100, 200 mg/kg bw/day in acetone for 5 days per week over a period of 13 weeks. A constant volume of 0.25 ml/rat was applied over a fixed standard area (10%) of the interscapular region. The area was clipped 24 hours prior to initial applic","page":17,"pdf":"sccp_o_078.pdf","row_type":"noael_study","study_id":"sccp_o_078_noael_007"}
SCCS_vision_codex	NOAEL	=200	mg/kg bw/day	rat	dermal	90d	NOAEL study	{"citation":"Ref.: 30 90-day dermal toxicity in mouse Ten B6C3F1 mice per sex and group received Benzophenone-3 preparations at dosage levels of 0, 22","dose":"SCCP/1069/06 OPINION ON BENZOPHENONE-3 18 200 mg/kg bw/day: non-dosage related increase in relative kidney weight in females; decreased reticulocyte count; increased platelet count; increased whole blood cell count produced by lymphocytosis Study authors' conclusion:","effect":"SCCP/1069/06 OPINION ON BENZOPHENONE-3 18 200 mg/kg bw/day: non-dosage related increase in relative kidney weight in females; decreased reticulocyte count; increased platelet count; increased whole blood cell count produced by lymphocytosis Study authors' conclusion: NOAEL (90d-dermal) = 200 mg/kg bw/day for male and female rats. Ref.: 30 90-day dermal toxicity in mouse Ten B6C3F1 mice per sex and group received Benzophenone-3 preparations at dosage levels of 0, 22.8, 45.5, 91, 182, 364 mg/kg bw/day in acetone for 5 days per week over a period of 13 weeks. A constant volume of 0.1 ml was applied over a fixed standard area (10%) of the interscapular region. The area was clipped 24 hours prior to initial application and weekly thereafter. The preparations in acetone were analyzed fo","page":18,"pdf":"sccp_o_078.pdf","row_type":"noael_study","study_id":"sccp_o_078_noael_008"}
SCCS_vision_codex	NOAEL	=364	mg/kg bw/day	rat	oral	90d	repeated dose toxicity	{"citation":"Ref.: 30 3","dose":"Sperm morphology/motility and vaginal cytology examinations were performed at dosage levels of 0, 22.8, 91, 364 mg/kg bw/day.","effect":"ll animals at regular intervals. Sperm morphology/motility and vaginal cytology examinations were performed at dosage levels of 0, 22.8, 91, 364 mg/kg bw/day. At termination of treatment, all animals were sacrificed and macroscopically examined, organs were weighed and comprehensive histopathology was performed. At all dosage levels, a mild increase in relative kidney weight in males, together with a decrease in epididymal sperm density, was noted. No other abnormalities were observed. Study authors' conclusion: NOAEL (90d-dermal) = 364 mg/kg bw/day for male and female mice. Ref.: 30 3.3.5.3 Chronic (> 12 months) toxicity No data. 3.3.5.4 Overall conclusion of the submission authors on repeated dose toxicity The toxicity of Benzophenone-3 after repeated application was comprehensively examined in subacute up to subchronic studies in rats and mice using the oral and dermal application route. The systemic toxicity after repeated oral application was low and effects could mainly be observed at dose levels which were in the ran","page":18,"pdf":"sccp_o_078.pdf","row_type":"noael_study","study_id":"sccp_o_078_noael_009"}
SCCS_vision_codex	NOAEL	=6250	ppm	rat	oral	subchronic	repeated dose toxicity	{"dose":"ly >3000 mg/kg bw/day in rats and >13000 mg/kg bw/day in mice after subchronic oral treatment, an impairment of selective reproductive parameters was noted.","effect":"ly >3000 mg/kg bw/day in rats and >13000 mg/kg bw/day in mice after subchronic oral treatment, an impairment of selective reproductive parameters was noted. However, these are finally assessed in the reproduction section within this dossier (section 3.3.8 Reproductive toxicity). Repeated dermal application of up to 13 weeks in rats and mice did not lead to any reliable substance-related local or systemic findings up to the highest dose level investigated in each case. Finally, the reliable No-Adverse-Effect-Level (NOAEL) for subchronic toxicity after oral treatment was 6250 ppm (429/393 mg/kg bw/day in males/females) in rats and 6250 ppm (1068/1425 mg/kg bw/day in males/females) in mice.","page":18,"pdf":"sccp_o_078.pdf","row_type":"noael_study","study_id":"sccp_o_078_noael_010"}
SCCS_vision_codex	NOAEL	=828	mg/kg bw/day	rat	oral	-	reproductive toxicity	{"citation":"Ref.: 24, 30","dose":"204 mg/kg bw/day: no deviations among the reproductive parameters studied 828 mg/kg bw/day: no deviations among the reproductive parameters studied 3,458 mg/kg bw/day: males: decreased right caudal, testicular and epididymal weights; decreased sperm number per caudal tissue females : prolonged cycle length.","effect":"ssue weight. Observations in the females included vaginal cytology examinations and estrual cyclicity. The following effects were noted (dietary levels were converted to dosages): 204 mg/kg bw/day: no deviations among the reproductive parameters studied 828 mg/kg bw/day: no deviations among the reproductive parameters studied 3,458 mg/kg bw/day: males: decreased right caudal, testicular and epididymal weights; decreased sperm number per caudal tissue females : prolonged cycle length. Study authors' conclusion: NOAEL (reproduction) = 828 mg/kg bw/day for male and female rats. Ref.: 24, 30","page":21,"pdf":"sccp_o_078.pdf","row_type":"noael_study","study_id":"sccp_o_078_noael_012"}
SCCS_vision_codex	NOAEL	=2860	mg/kg bw/day	mouse	oral	-	reproductive toxicity	{"citation":"Ref.: 24, 30 Reproductive Assessment by Continuous Breeding (RACB) in the mouse (1991) The \"Continuous Breeding Protocol\" is a test design used by the US National Toxicology Program","dose":"554 mg/kg bw/day: no deviations among the reproductive parameters studied 2,860 mg/kg bw/day: no deviations among the reproductive parameters studied 16,238 mg/kg bw/day: decreased sperm number per caudal tissue and increased incidence of abnormal sperm in the males Study authors' conclusion:","effect":"d morphology and sperm number per caudal tissue weight. Observations in the females included vaginal cytology examinations and estrual cyclicity. The following effects were noted (dietary levels were converted to dosages): 554 mg/kg bw/day: no deviations among the reproductive parameters studied 2,860 mg/kg bw/day: no deviations among the reproductive parameters studied 16,238 mg/kg bw/day: decreased sperm number per caudal tissue and increased incidence of abnormal sperm in the males Study authors' conclusion: NOAEL (reproduction) = 2,860 mg/kg bw/day for male and female mice. Ref.: 24, 30 Reproductive Assessment by Continuous Breeding (RACB) in the mouse (1991) The \"Continuous Breeding Protocol\" is a test design used by the US National Toxicology Program. It consists of four related tasks (see figure below), which are not all necessarily performed for every compound tested. TASK 4 Offspring assessment F1 generation (Control + 1 dosed group) TASK 3 Determination of affected sex (F0 generation) TASK 4 Offspring assessment F","page":22,"pdf":"sccp_o_078.pdf","row_type":"noael_study","study_id":"sccp_o_078_noael_013"}
SCCS_vision_codex	NOAEL	=9500	mg/kg bw/day	mouse	dermal	20-day	reproductive toxicity	{"citation":"Ref.: 9, 31 B","dose":"5 dams died unexpectedly during the Task 2 20-day period 3,950 mg/kg bw/day: reduced number of pups / litter; reduced dam weights;","effect":"ation, necropsy was performed, organs were weighed and preserved for histopathology (especially reproductive organs). The following effects were noted: 1,850 mg/kg bw/day: 5 dams died unexpectedly during the Task 2 20-day period 3,950 mg/kg bw/day: reduced number of pups / litter; reduced dam weights; 4 dams died unexpectedly during the Task 2 20-day period 9,050mg/kg bw/day: reduced number of pups / litter; reduced dam weights; 9 dams died unexpectedly during the Task 2 20-day period Study authors' conclusion: NOAEL (fertility) = 8600/9500 mg/kg bw/day for male/female mice. Ref.: 9, 31 B. Dermal reproduction toxicity screening tests A short communication published in 1993 describes the assessment of the reproductive toxic potential of Benzophenone-3 in male B6C3F1 mice after a 13-week repeated dermal application of dosages of 0, 20, 100 and 400 mg/kg bw/day. Reproductive organ weights, cauda epididymal sperm concentration, proportion of motile and abnormal sperm and testicular spermatid concentration were determined and tes","page":23,"pdf":"sccp_o_078.pdf","row_type":"noael_study","study_id":"sccp_o_078_noael_014"}
SCCS_vision_codex	NOAEL	=400	mg/kg bw/day	mouse	oral	sub-chronic	repeated dose toxicity	{"citation":"Ref.: 21 Finally, the results of the examinations of sperm morphology/motility and vaginal cytology in the dermal sub-chronic toxicity studies as described under 3","dose":"Since neither any effect on body weight gain nor any abnormalities in the measured reproductive parameters were noted, the study authors conclude that topically applied Benzophenone-3 has no reproductive toxic potential in male B6C3F1 mice at dosages up to 400 mg/kg bw/day.","effect":"0 mg/kg bw/day. Reproductive organ weights, cauda epididymal sperm concentration, proportion of motile and abnormal sperm and testicular spermatid concentration were determined and testicular histology was evaluated. Since neither any effect on body weight gain nor any abnormalities in the measured reproductive parameters were noted, the study authors conclude that topically applied Benzophenone-3 has no reproductive toxic potential in male B6C3F1 mice at dosages up to 400 mg/kg bw/day. Study authors' conclusion: NOAEL (reproduction) = 400 mg/kg bw/day for male and female mice. Ref.: 21 Finally, the results of the examinations of sperm morphology/motility and vaginal cytology in the dermal sub-chronic toxicity studies as described under 3.3.5.2.B, revealed a decrease in epididymal sperm density in the male mice. However, this finding is considered incidental 3 Stability of Benzophenone-3 in the diet : at least 3 weeks","page":23,"pdf":"sccp_o_078.pdf","row_type":"noael_study","study_id":"sccp_o_078_noael_015"}
SCCS_vision_codex	NOAEL	=1900	mg/kg bw/day	rat	oral	developmental	reproductive toxicity	{"dose":"The NOAEL for fertility was the highest investigated dosage level of 8600/9500 mg/kg bw/day in male/female mice.","effect":"a RACB (Reproductive Assessment by Continuous Breeding) study in mice. The NOAEL for fertility was the highest investigated dosage level of 8600/9500 mg/kg bw/day in male/female mice. Within this study the reproductive performance was affected in the form of a slightly lower number of live pups at birth. Signs of developmental toxicity consisted of impaired body weight/body weight gain of the pups. However, in any case these effects were only noted at a dosage level with overt parental toxicity. Consequently, the NOAEL for systemic, reproductive and developmental toxicity was 1800/1900 mg/kg bw/day in males/females. Repeated oral application of Benzophenone-3 for 13 weeks to rats and mice caused only slight effects in selective parameters accompanied with overt systemic toxicity at the highest investigated dosage levels of 3656/3261 mg/kg bw/day in male/female rats and 13937/18539 mg/kg bw/day in male/female mice). In rats, the epididymal sperm count was reduced and a decreased absolute cauda, epididymal and testis weight as a","page":25,"pdf":"sccp_o_078.pdf","row_type":"noael_study","study_id":"sccp_o_078_noael_019"}
SCCS_vision_codex	NOAEL	=200	mg/kg bw/d	rat	oral	subchronic	repeated dose toxicity	{"dose":"In any case, the next lower investigated dose level was a clear NOAEL for the investigated reproductive parameters.","effect":"ecreased absolute cauda, epididymal and testis weight as a consequence of the reduced body weight was noted. In female rats, an increase in the length of the oestrous cycle was noted. In mice, a decrease in the epididymal sperm count and an increase the incidence of abnormal sperm was recorded, while female mice (as in rats) revealed an increase in the length of the oestrous cycle. However, in rats and in mice, the oestrous cyclicity was not affected. In any case, the next lower investigated dose level was a clear NOAEL for the investigated reproductive parameters. After subchronic dermal application for 13 weeks no clear or reliable effect on selective reproduction parameter was noted and therefore, the NOAEL was in each case the highest dose level applied, namely 200 mg/kg bw/d in rats and 364 mg/kg bw/d in mice. Although in mice a decrease in the epididymal sperm count was reported at all investigated dose levels, a relation to treatment is considered as very unlikely since in the oral study the administration of dose levels","page":25,"pdf":"sccp_o_078.pdf","row_type":"noael_study","study_id":"sccp_o_078_noael_020"}
SCCS_vision_codex	NOAEL	=411	mg/kg bw/day	rat	oral	90d	repeated dose toxicity	{"dose":"Therefore, according to the submission, the oral NOAEL corresponds to 411 mg/kg bw/day.","effect":"SCCS-rejected applicant NOAEL: ether with some effects on the identified target organs being the kidney and the liver. These effects were partly associated with changes in clinical chemistry. Very often the most susceptible parameter was the increase in liver weight. The latter, however, without any histopathological correlate, is not considered by the submission authors to reflect an adverse effect per se but should be considered as an adaptive metabolic response which is known to be reversible. Therefore, according to the submission, the oral NOAEL corresponds to 411 mg/kg bw/day. With regard to the results of the dermal repeated dose studies, a dermal NOAEL of 200 mg/kg bw/day is put forward, on the assumption that deviations without dose-response relationship and without correlated histopathological findings (e.g. the decreased reticulocyte count, increased relative kidney weight, increased platelet count and whole blood cell count in the 90d dermal study in rat) should not be taken into account.","page":35,"pdf":"sccp_o_078.pdf","row_type":"noael_study","study_id":"sccp_o_078_noael_023"}
SCCS_vision_codex	NOAEL	=18	-	-	oral	subchronic	repeated dose toxicity	{"effect":"Unlabeled table on page 18: Finally, the reliable No-Adverse-Effect-Level (NOAEL) for subchronic toxicity after oral","page":18,"pdf":"sccp_o_078.pdf","row_type":"noael_study","study_id":"sccp_o_078_noael_036"}
SCCS_vision_codex	NOAEL	=1980	-	-	-	-	NOAEL study	{"effect":"Unlabeled table on page 19: A number of publications (1980-1992) describe the results of Benzophenone-3 studied in","page":19,"pdf":"sccp_o_078.pdf","row_type":"noael_study","study_id":"sccp_o_078_noael_038"}
SCCS_vision_codex	NOAEL	=36	-	-	-	-	NOAEL study	{"effect":"Unlabeled table on page 19: and a title page [36] to a more extensive description of the materials and methods [73].","page":19,"pdf":"sccp_o_078.pdf","row_type":"noael_study","study_id":"sccp_o_078_noael_039"}
SCCS_vision_codex	NOAEL	=9	-	-	-	-	NOAEL study	{"effect":"Unlabeled table on page 19: bacteria both, with and without metabolic activation (S9 mix from the liver of Aroclor 1254-","page":19,"pdf":"sccp_o_078.pdf","row_type":"noael_study","study_id":"sccp_o_078_noael_040"}
SCCS_vision_codex	NOAEL	=10	%	-	-	-	NOAEL study	{"effect":"Unlabeled table on page 19: prepared immediately prior to use and contained 10% S9. The tested Salmonella","page":19,"pdf":"sccp_o_078.pdf","row_type":"noael_study","study_id":"sccp_o_078_noael_041"}
SCCS_vision_codex	NOAEL	=97	-	-	-	-	NOAEL study	{"effect":"Unlabeled table on page 19: typhimurium strains were combinations of TA97, TA98, TA100, TA1535, TA1537 and/or","page":19,"pdf":"sccp_o_078.pdf","row_type":"noael_study","study_id":"sccp_o_078_noael_042"}
SCCS_vision_codex	NOAEL	=1538	-	-	-	-	NOAEL study	{"effect":"Unlabeled table on page 19: TA1538 and were exposed to the test substance at various concentrations of","page":19,"pdf":"sccp_o_078.pdf","row_type":"noael_study","study_id":"sccp_o_078_noael_043"}
SCCS_vision_codex	NOAEL	=-3	-	-	-	-	NOAEL study	{"effect":"Unlabeled table on page 19: Benzophenone-3 with and without S9 mix. Positive controls were included to demonstrate","page":19,"pdf":"sccp_o_078.pdf","row_type":"noael_study","study_id":"sccp_o_078_noael_044"}
SCCS_vision_codex	NOAEL	=73	-	-	-	-	NOAEL study	{"effect":"Unlabeled table on page 19: Bacteriotoxicity was reported [73] to be observed at a varying degree at and above 333","page":19,"pdf":"sccp_o_078.pdf","row_type":"noael_study","study_id":"sccp_o_078_noael_045"}
SCCS_vision_codex	NOAEL	=1000	-	-	-	-	NOAEL study	{"effect":"Unlabeled table on page 19: µg/plate and at 1000 µg/plate in all tested strains (TA98, TA100, TA1535, TA1537). In that","page":19,"pdf":"sccp_o_078.pdf","row_type":"noael_study","study_id":"sccp_o_078_noael_046"}
SCCS_vision_codex	NOAEL	=30	%	-	-	-	NOAEL study	{"effect":"Unlabeled table on page 19: weak mutagenic response using 30% of S9 hamster mix.","page":19,"pdf":"sccp_o_078.pdf","row_type":"noael_study","study_id":"sccp_o_078_noael_048"}
SCCS_vision_codex	NOAEL	=2	-	-	-	-	NOAEL study	{"effect":"Unlabeled table on page 19: the respective controls, the increase in the numbers of revertants was less than 2-fold","page":19,"pdf":"sccp_o_078.pdf","row_type":"noael_study","study_id":"sccp_o_078_noael_050"}
SCCS_vision_codex	NOAEL	=3	-	-	-	-	NOAEL study	{"effect":"Unlabeled table on page 19: the tested concentration range between 3 and 333 µg/plate. All other studies (not including","page":19,"pdf":"sccp_o_078.pdf","row_type":"noael_study","study_id":"sccp_o_078_noael_052"}
SCCS_vision_codex	NOAEL	=8	-	-	-	-	NOAEL study	{"citation":"Ref.: 8, 30, 36, 73","effect":"Unlabeled table on page 19: Ref.: 8, 30, 36, 73","page":19,"pdf":"sccp_o_078.pdf","row_type":"noael_study","study_id":"sccp_o_078_noael_057"}
SCCS_vision_codex	NOAEL	=1992	-	-	-	-	NOAEL study	{"effect":"Unlabeled table on page 19: A US National Toxicology program report (1992) briefly describes the results of cytogenetic","page":19,"pdf":"sccp_o_078.pdf","row_type":"noael_study","study_id":"sccp_o_078_noael_058"}
SCCS_vision_codex	NOAEL	=5	-	-	-	-	NOAEL study	{"dose":"Unlabeled table on page 19: exchanges (effective dose range 5-50µg/ml) and chromosomal aberrations (20-45µg/ml) in","effect":"Unlabeled table on page 19: exchanges (effective dose range 5-50µg/ml) and chromosomal aberrations (20-45µg/ml) in","page":19,"pdf":"sccp_o_078.pdf","row_type":"noael_study","study_id":"sccp_o_078_noael_060"}
SCCS_vision_codex	NOAEL	=1254	-	rat	-	-	NOAEL study	{"effect":"Unlabeled table on page 19: the presence of Aroclor 1254-induced male Sprague Dawley rat liver S9.","page":19,"pdf":"sccp_o_078.pdf","row_type":"noael_study","study_id":"sccp_o_078_noael_061"}
SCCS_vision_codex	NOAEL	=24	-	-	-	prenatal	developmental toxicity	{"effect":"Unlabeled table on page 24: effect and that the NOAEL for maternal and prenatal developmental toxicity is","page":24,"pdf":"sccp_o_078.pdf","row_type":"noael_study","study_id":"sccp_o_078_noael_066"}
SCCS_vision_codex	NOAEL	=1	-	-	-	-	NOAEL study	{"effect":"Unlabeled table on page 24: Date of study: 01-16 November 2004","page":24,"pdf":"sccp_o_078.pdf","row_type":"noael_study","study_id":"sccp_o_078_noael_069"}
SCCS_vision_codex	NOAEL	=67	-	-	-	-	NOAEL study	{"effect":"Unlabeled table on page 24: Guideline/method: Annex V to Dir. 67/548/EEC, Method B.31; OECD Guideline 414","page":24,"pdf":"sccp_o_078.pdf","row_type":"noael_study","study_id":"sccp_o_078_noael_070"}
SCCS_vision_codex	NOAEL	=25	-	-	-	-	NOAEL study	{"effect":"Unlabeled table on page 24: Group size: 25 mated females per dosage group","page":24,"pdf":"sccp_o_078.pdf","row_type":"noael_study","study_id":"sccp_o_078_noael_071"}
SCCS_vision_codex	NOAEL	=99.8	%	-	-	-	NOAEL study	{"effect":"Unlabeled table on page 24: Purity: 99.8% (GC-FID)","page":24,"pdf":"sccp_o_078.pdf","row_type":"noael_study","study_id":"sccp_o_078_noael_073"}
SCCS_vision_codex	NOAEL	=35	-	-	oral	-	NOAEL study	{"effect":"Unlabeled table on page 35: reversible. Therefore, according to the submission, the oral NOAEL corresponds to","page":35,"pdf":"sccp_o_078.pdf","row_type":"noael_study","study_id":"sccp_o_078_noael_080"}
SCCS_vision_codex	NOAEL	=311	mg/kg bw/day	rat	oral	14d	NOAEL study	{"citation":"Ref.: 30 14-day oral toxicity in mouse (1985-88) Benzophenone-3 was administered in the diet to five B6C3F1 mice per sex and group at concentrations of 0, 3,125","dose":"2,238 mg/kg bw/day: increased liver weights in males and females associated with the presence of cytoplasmic vacuolisation of hepatocytes; increased kidney weights in males 3,868 mg/kg bw/day: reduced feed consumption in males and females; reduced body weight gain in males; increased liver weights in males and females associated with the presenc...","effect":"2,238 mg/kg bw/day: increased liver weights in males and females associated with the presence of cytoplasmic vacuolisation of hepatocytes; increased kidney weights in males 3,868 mg/kg bw/day: reduced feed consumption in males and females; reduced body weight gain in males; increased liver weights in males and females associated with the presence of cytoplasmic vacuolisation of hepatocytes; increased kidney weights in males; focal dilatation of renal tubules in the cortex and/or medulla Study authors' conclusion: NOAEL (14d-oral) = 295/311 mg/kg bw/day for the male/female rat. Ref.: 30 14-day oral toxicity in mouse (1985-88) Benzophenone-3 was administered in the diet to five B6C3F1 mice per sex and group at concentrations of 0, 3,125; 6,250; 12,500; 25,000 and 50,000 ppm for 2 weeks. The dietary test substance preparations were analyzed for stability and proved to be stable in the diet for at least 3 weeks. Clinical examinations covering clinical signs, mortality, body weight and food consumption were performed in all animals","page":12,"pdf":"sccp_o_078.pdf","row_type":"noael_study","study_id":"sccp_o_078_noael_001"}
SCCS_vision_codex	NOAEL	=1050	mg/kg bw/day	rat	oral	14d	repeated dose toxicity	{"citation":"Ref.: 30 B","dose":"y: increased liver weights in males and females associated with the presence of cytoplasmic vacuolisation of hepatocytes 8,648 mg/kg bw/day: increased liver weights in males and females associated with the presence of cytoplasmic vacuolisation of hepatocytes; decreased kidney weight in males 20,796 mg/kg bw/day: reduced body weight gain; increas...","effect":"y: increased liver weights in males and females associated with the presence of cytoplasmic vacuolisation of hepatocytes 8,648 mg/kg bw/day: increased liver weights in males and females associated with the presence of cytoplasmic vacuolisation of hepatocytes; decreased kidney weight in males 20,796 mg/kg bw/day: reduced body weight gain; increased liver weights in males and females associated with the presence of cytoplasmic vacuolisation of hepatocytes; decreased kidney weight in males Study authors' conclusion: NOAEL (14d-oral) = 992/1050 mg/kg bw/day for the male/female mouse. Ref.: 30 B. Subacute dermal administration to rats and mice 14-day dermal toxicity in rat (1985-88) Five F344/N rats per sex and group received Benzophenone-3 at dose levels of 0, 1.25, 2.5, 5.0, 10.0, 20.0 mg/rat in acetone or lotion as vehicle for 5 days per week for 2 weeks. A constant volume of 0.25 ml/rat was applied over a fixed standard area (10%) of the interscapular region. The area was clipped 24 hours prior to initial application and weekl","page":13,"pdf":"sccp_o_078.pdf","row_type":"noael_study","study_id":"sccp_o_078_noael_002"}
SCCS_vision_codex	NOAEL	=140	mg/kg bw/day	rat	oral	14d	NOAEL study	{"citation":"Ref.: 30 28-day dermal toxicity in rat (1985-88) A publication of 1995 describes how 6 male Sprague-Dawley rats per group received Benzophenone-3, formulated in petroleum jelly base, at","dose":"7.0 mg/kg bw/day: no adverse effects noted 13.6 mg/kg bw/day: no adverse effects noted 27.7 mg/kg bw/day: slightly increased liver weights in females 54.9 mg/kg bw/day: slightly increased liver weights in female 110 mg/kg bw/day: slightly increased liver weights in females; slightly increased kidney weights Study authors' conclusion:","effect":"ficed and macroscopically examined, organs were weighed and comprehensive histopathology was performed. The following effects were noted (dietary levels were converted to dosages): 7.0 mg/kg bw/day: no adverse effects noted 13.6 mg/kg bw/day: no adverse effects noted 27.7 mg/kg bw/day: slightly increased liver weights in females 54.9 mg/kg bw/day: slightly increased liver weights in female 110 mg/kg bw/day: slightly increased liver weights in females; slightly increased kidney weights Study authors' conclusion: NOAEL (14d-dermal) = 100/140 mg/kg bw/day for the male/female rat. Ref.: 30 28-day dermal toxicity in rat (1985-88) A publication of 1995 describes how 6 male Sprague-Dawley rats per group received Benzophenone-3, formulated in petroleum jelly base, at dosage levels of 0 and 100 mg/kg bw/day, twice daily for 4 weeks. Clinical examinations covering clinical signs and body weight were performed in all animals. Blood samples for haematology and clinical chemistry were taken prior to the start of treatment and on day 16.","page":13,"pdf":"sccp_o_078.pdf","row_type":"noael_study","study_id":"sccp_o_078_noael_003"}
SCCS_vision_codex	NOAEL	=432	mg/kg bw/day	rat	oral	14d	repeated dose toxicity	{"citation":"Ref.: 30 3","dose":"24.8 mg/kg bw/day: none 48.4 mg/kg bw/day: none 100 mg/kg bw/day: none 196 mg/kg bw/day: increased liver weight 388 mg/kg bw/day: increased liver weight Study authors' conclusion:","effect":"tions covering clinical signs, mortality, body weight and food consumption were performed in all animals. At termination of treatment, all animals were sacrificed and macroscopically examined, organs were weighed and comprehensive histopathology was performed. The following effects were noted (applied doses were converted to dosages): 24.8 mg/kg bw/day: none 48.4 mg/kg bw/day: none 100 mg/kg bw/day: none 196 mg/kg bw/day: increased liver weight 388 mg/kg bw/day: increased liver weight Study authors' conclusion: NOAEL (14d-dermal) = 384/432 mg/kg bw/day for the male/female mouse. Ref.: 30 3.3.5.2 Sub-chronic (90 days) oral / dermal / inhalation toxicity - rat/mouse A. Sub-chronic oral administration to rats and mice 90-day oral toxicity in rat (1) (1972) Benzophenone-3 (source and batch not cited) was examined in 12 male and 12 female rats per sex and group at dosages of approximately 0, 20, 100, 500 and 1,000 mg/kg bw/day for 13 weeks. The animals were observed for clinical findings and body weight and food consumption was","page":14,"pdf":"sccp_o_078.pdf","row_type":"noael_study","study_id":"sccp_o_078_noael_004"}
SCCS_vision_codex	NOAEL	=100	mg/kg bw/day	rat	oral	12 weeks	NOAEL study	{"citation":"Ref.: 44 90-day oral toxicity in rat (2) (1985-1988) Ten F344/N rats per sex and group received Benzophenone-3 in concentrations of 0","dose":"NOEL (90d-oral) = 100 mg/kg bw/day for male and female rats.","effect":"males; anaemia, lymphocytosis and reduced number of granulocytes after 12 weeks in females; decreased absolute weights of the thymus, heart, pituitary gland, lungs, spleen, adrenal glands, and gonads in males and females; decreased relative weights of the pituitary gland, thymus, heart and adrenal glands in males and females; decreased relative weights of the lungs and spleen in females; increased relative thyroid weight in females; degenerative nephritis in kidneys of males and females Study authors' conclusion: NOEL (90d-oral) = 100 mg/kg bw/day for male and female rats. Ref.: 44 90-day oral toxicity in rat (2) (1985-1988) Ten F344/N rats per sex and group received Benzophenone-3 in concentrations of 0; 3,125; 6,250; 12,500; 25,000 and 50,000 ppm in the diet for 13 weeks. The dietary test substance preparations were analyzed for stability and proved to be stable in the diet for at least 3 weeks. Clinical examinations covering clinical signs, mortality, body weight and food consumption were performed in all animals at regula","page":15,"pdf":"sccp_o_078.pdf","row_type":"noael_study","study_id":"sccp_o_078_noael_005"}
SCCS_vision_codex	NOAEL	=393	mg/kg bw/day	rat	oral	90d	NOAEL study	{"citation":"Ref.: 30","dose":"NOAEL (90d-oral) = 429/393 mg/kg bw/day for the male/female rat.","effect":"SCCP/1069/06 OPINION ON BENZOPHENONE-3 16 Study authors' conclusion: NOAEL (90d-oral) = 429/393 mg/kg bw/day for the male/female rat. Ref.: 30","page":16,"pdf":"sccp_o_078.pdf","row_type":"noael_study","study_id":"sccp_o_078_noael_006"}
SCCS_vision_codex	NOAEL	=1425	mg/kg bw/day	rat	oral	90d	repeated dose toxicity	{"citation":"Ref.: 30 B","dose":"y: increased liver weight 2,860 mg/kg bw/day: increased liver weight 6,780 mg/kg bw/day: decreased body weight gain in males and females; increased liver weight; minimal cytoplasmic vacuolisation of hepatocytes 16,238 mg/kg bw/day: decreased body weight gain in males and females; minimal renal lesions in males; increased liver weight; minimal cy...","effect":"y: increased liver weight 2,860 mg/kg bw/day: increased liver weight 6,780 mg/kg bw/day: decreased body weight gain in males and females; increased liver weight; minimal cytoplasmic vacuolisation of hepatocytes 16,238 mg/kg bw/day: decreased body weight gain in males and females; minimal renal lesions in males; increased liver weight; minimal cytoplasmic vacuolisation of hepatocytes; decreased sperm density and increased abnormal sperm in males; increased estrous cycle length in females Study authors' conclusion: NOAEL (90d-oral) = 1068/1425 mg/kg bw/day for the male/female mouse. Ref.: 30 B. Sub-chronic dermal administration to rats and mice 90-day dermal toxicity in rat (1985-88) Ten F344/N rats per sex and groups received Benzophenone-3 preparations at dosage levels of 0, 12.5, 25, 50, 100, 200 mg/kg bw/day in acetone for 5 days per week over a period of 13 weeks. A constant volume of 0.25 ml/rat was applied over a fixed standard area (10%) of the interscapular region. The area was clipped 24 hours prior to initial applic","page":17,"pdf":"sccp_o_078.pdf","row_type":"noael_study","study_id":"sccp_o_078_noael_007"}
SCCS_vision_codex	NOAEL	=200	mg/kg bw/day	rat	dermal	90d	NOAEL study	{"citation":"Ref.: 30 90-day dermal toxicity in mouse Ten B6C3F1 mice per sex and group received Benzophenone-3 preparations at dosage levels of 0, 22","dose":"SCCP/1069/06 OPINION ON BENZOPHENONE-3 18 200 mg/kg bw/day: non-dosage related increase in relative kidney weight in females; decreased reticulocyte count; increased platelet count; increased whole blood cell count produced by lymphocytosis Study authors' conclusion:","effect":"SCCP/1069/06 OPINION ON BENZOPHENONE-3 18 200 mg/kg bw/day: non-dosage related increase in relative kidney weight in females; decreased reticulocyte count; increased platelet count; increased whole blood cell count produced by lymphocytosis Study authors' conclusion: NOAEL (90d-dermal) = 200 mg/kg bw/day for male and female rats. Ref.: 30 90-day dermal toxicity in mouse Ten B6C3F1 mice per sex and group received Benzophenone-3 preparations at dosage levels of 0, 22.8, 45.5, 91, 182, 364 mg/kg bw/day in acetone for 5 days per week over a period of 13 weeks. A constant volume of 0.1 ml was applied over a fixed standard area (10%) of the interscapular region. The area was clipped 24 hours prior to initial application and weekly thereafter. The preparations in acetone were analyzed fo","page":18,"pdf":"sccp_o_078.pdf","row_type":"noael_study","study_id":"sccp_o_078_noael_008"}
SCCS_vision_codex	NOAEL	=364	mg/kg bw/day	rat	oral	90d	repeated dose toxicity	{"citation":"Ref.: 30 3","dose":"Sperm morphology/motility and vaginal cytology examinations were performed at dosage levels of 0, 22.8, 91, 364 mg/kg bw/day.","effect":"ll animals at regular intervals. Sperm morphology/motility and vaginal cytology examinations were performed at dosage levels of 0, 22.8, 91, 364 mg/kg bw/day. At termination of treatment, all animals were sacrificed and macroscopically examined, organs were weighed and comprehensive histopathology was performed. At all dosage levels, a mild increase in relative kidney weight in males, together with a decrease in epididymal sperm density, was noted. No other abnormalities were observed. Study authors' conclusion: NOAEL (90d-dermal) = 364 mg/kg bw/day for male and female mice. Ref.: 30 3.3.5.3 Chronic (> 12 months) toxicity No data. 3.3.5.4 Overall conclusion of the submission authors on repeated dose toxicity The toxicity of Benzophenone-3 after repeated application was comprehensively examined in subacute up to subchronic studies in rats and mice using the oral and dermal application route. The systemic toxicity after repeated oral application was low and effects could mainly be observed at dose levels which were in the ran","page":18,"pdf":"sccp_o_078.pdf","row_type":"noael_study","study_id":"sccp_o_078_noael_009"}
SCCS_vision_codex	NOAEL	=6250	ppm	rat	oral	subchronic	repeated dose toxicity	{"dose":"ly >3000 mg/kg bw/day in rats and >13000 mg/kg bw/day in mice after subchronic oral treatment, an impairment of selective reproductive parameters was noted.","effect":"ly >3000 mg/kg bw/day in rats and >13000 mg/kg bw/day in mice after subchronic oral treatment, an impairment of selective reproductive parameters was noted. However, these are finally assessed in the reproduction section within this dossier (section 3.3.8 Reproductive toxicity). Repeated dermal application of up to 13 weeks in rats and mice did not lead to any reliable substance-related local or systemic findings up to the highest dose level investigated in each case. Finally, the reliable No-Adverse-Effect-Level (NOAEL) for subchronic toxicity after oral treatment was 6250 ppm (429/393 mg/kg bw/day in males/females) in rats and 6250 ppm (1068/1425 mg/kg bw/day in males/females) in mice.","page":18,"pdf":"sccp_o_078.pdf","row_type":"noael_study","study_id":"sccp_o_078_noael_010"}
SCCS_vision_codex	NOAEL	=828	mg/kg bw/day	rat	oral	-	reproductive toxicity	{"citation":"Ref.: 24, 30","dose":"204 mg/kg bw/day: no deviations among the reproductive parameters studied 828 mg/kg bw/day: no deviations among the reproductive parameters studied 3,458 mg/kg bw/day: males: decreased right caudal, testicular and epididymal weights; decreased sperm number per caudal tissue females : prolonged cycle length.","effect":"ssue weight. Observations in the females included vaginal cytology examinations and estrual cyclicity. The following effects were noted (dietary levels were converted to dosages): 204 mg/kg bw/day: no deviations among the reproductive parameters studied 828 mg/kg bw/day: no deviations among the reproductive parameters studied 3,458 mg/kg bw/day: males: decreased right caudal, testicular and epididymal weights; decreased sperm number per caudal tissue females : prolonged cycle length. Study authors' conclusion: NOAEL (reproduction) = 828 mg/kg bw/day for male and female rats. Ref.: 24, 30","page":21,"pdf":"sccp_o_078.pdf","row_type":"noael_study","study_id":"sccp_o_078_noael_012"}
SCCS_vision_codex	NOAEL	=2860	mg/kg bw/day	mouse	oral	-	reproductive toxicity	{"citation":"Ref.: 24, 30 Reproductive Assessment by Continuous Breeding (RACB) in the mouse (1991) The \"Continuous Breeding Protocol\" is a test design used by the US National Toxicology Program","dose":"554 mg/kg bw/day: no deviations among the reproductive parameters studied 2,860 mg/kg bw/day: no deviations among the reproductive parameters studied 16,238 mg/kg bw/day: decreased sperm number per caudal tissue and increased incidence of abnormal sperm in the males Study authors' conclusion:","effect":"d morphology and sperm number per caudal tissue weight. Observations in the females included vaginal cytology examinations and estrual cyclicity. The following effects were noted (dietary levels were converted to dosages): 554 mg/kg bw/day: no deviations among the reproductive parameters studied 2,860 mg/kg bw/day: no deviations among the reproductive parameters studied 16,238 mg/kg bw/day: decreased sperm number per caudal tissue and increased incidence of abnormal sperm in the males Study authors' conclusion: NOAEL (reproduction) = 2,860 mg/kg bw/day for male and female mice. Ref.: 24, 30 Reproductive Assessment by Continuous Breeding (RACB) in the mouse (1991) The \"Continuous Breeding Protocol\" is a test design used by the US National Toxicology Program. It consists of four related tasks (see figure below), which are not all necessarily performed for every compound tested. TASK 4 Offspring assessment F1 generation (Control + 1 dosed group) TASK 3 Determination of affected sex (F0 generation) TASK 4 Offspring assessment F","page":22,"pdf":"sccp_o_078.pdf","row_type":"noael_study","study_id":"sccp_o_078_noael_013"}
SCCS_vision_codex	NOAEL	=9500	mg/kg bw/day	mouse	dermal	20-day	reproductive toxicity	{"citation":"Ref.: 9, 31 B","dose":"5 dams died unexpectedly during the Task 2 20-day period 3,950 mg/kg bw/day: reduced number of pups / litter; reduced dam weights;","effect":"ation, necropsy was performed, organs were weighed and preserved for histopathology (especially reproductive organs). The following effects were noted: 1,850 mg/kg bw/day: 5 dams died unexpectedly during the Task 2 20-day period 3,950 mg/kg bw/day: reduced number of pups / litter; reduced dam weights; 4 dams died unexpectedly during the Task 2 20-day period 9,050mg/kg bw/day: reduced number of pups / litter; reduced dam weights; 9 dams died unexpectedly during the Task 2 20-day period Study authors' conclusion: NOAEL (fertility) = 8600/9500 mg/kg bw/day for male/female mice. Ref.: 9, 31 B. Dermal reproduction toxicity screening tests A short communication published in 1993 describes the assessment of the reproductive toxic potential of Benzophenone-3 in male B6C3F1 mice after a 13-week repeated dermal application of dosages of 0, 20, 100 and 400 mg/kg bw/day. Reproductive organ weights, cauda epididymal sperm concentration, proportion of motile and abnormal sperm and testicular spermatid concentration were determined and tes","page":23,"pdf":"sccp_o_078.pdf","row_type":"noael_study","study_id":"sccp_o_078_noael_014"}
SCCS_vision_codex	NOAEL	=400	mg/kg bw/day	mouse	oral	sub-chronic	repeated dose toxicity	{"citation":"Ref.: 21 Finally, the results of the examinations of sperm morphology/motility and vaginal cytology in the dermal sub-chronic toxicity studies as described under 3","dose":"Since neither any effect on body weight gain nor any abnormalities in the measured reproductive parameters were noted, the study authors conclude that topically applied Benzophenone-3 has no reproductive toxic potential in male B6C3F1 mice at dosages up to 400 mg/kg bw/day.","effect":"0 mg/kg bw/day. Reproductive organ weights, cauda epididymal sperm concentration, proportion of motile and abnormal sperm and testicular spermatid concentration were determined and testicular histology was evaluated. Since neither any effect on body weight gain nor any abnormalities in the measured reproductive parameters were noted, the study authors conclude that topically applied Benzophenone-3 has no reproductive toxic potential in male B6C3F1 mice at dosages up to 400 mg/kg bw/day. Study authors' conclusion: NOAEL (reproduction) = 400 mg/kg bw/day for male and female mice. Ref.: 21 Finally, the results of the examinations of sperm morphology/motility and vaginal cytology in the dermal sub-chronic toxicity studies as described under 3.3.5.2.B, revealed a decrease in epididymal sperm density in the male mice. However, this finding is considered incidental 3 Stability of Benzophenone-3 in the diet : at least 3 weeks","page":23,"pdf":"sccp_o_078.pdf","row_type":"noael_study","study_id":"sccp_o_078_noael_015"}
SCCS_vision_codex	NOAEL	=1900	mg/kg bw/day	rat	oral	developmental	reproductive toxicity	{"dose":"The NOAEL for fertility was the highest investigated dosage level of 8600/9500 mg/kg bw/day in male/female mice.","effect":"a RACB (Reproductive Assessment by Continuous Breeding) study in mice. The NOAEL for fertility was the highest investigated dosage level of 8600/9500 mg/kg bw/day in male/female mice. Within this study the reproductive performance was affected in the form of a slightly lower number of live pups at birth. Signs of developmental toxicity consisted of impaired body weight/body weight gain of the pups. However, in any case these effects were only noted at a dosage level with overt parental toxicity. Consequently, the NOAEL for systemic, reproductive and developmental toxicity was 1800/1900 mg/kg bw/day in males/females. Repeated oral application of Benzophenone-3 for 13 weeks to rats and mice caused only slight effects in selective parameters accompanied with overt systemic toxicity at the highest investigated dosage levels of 3656/3261 mg/kg bw/day in male/female rats and 13937/18539 mg/kg bw/day in male/female mice). In rats, the epididymal sperm count was reduced and a decreased absolute cauda, epididymal and testis weight as a","page":25,"pdf":"sccp_o_078.pdf","row_type":"noael_study","study_id":"sccp_o_078_noael_019"}
SCCS_vision_codex	NOAEL	=200	mg/kg bw/d	rat	oral	subchronic	repeated dose toxicity	{"dose":"In any case, the next lower investigated dose level was a clear NOAEL for the investigated reproductive parameters.","effect":"ecreased absolute cauda, epididymal and testis weight as a consequence of the reduced body weight was noted. In female rats, an increase in the length of the oestrous cycle was noted. In mice, a decrease in the epididymal sperm count and an increase the incidence of abnormal sperm was recorded, while female mice (as in rats) revealed an increase in the length of the oestrous cycle. However, in rats and in mice, the oestrous cyclicity was not affected. In any case, the next lower investigated dose level was a clear NOAEL for the investigated reproductive parameters. After subchronic dermal application for 13 weeks no clear or reliable effect on selective reproduction parameter was noted and therefore, the NOAEL was in each case the highest dose level applied, namely 200 mg/kg bw/d in rats and 364 mg/kg bw/d in mice. Although in mice a decrease in the epididymal sperm count was reported at all investigated dose levels, a relation to treatment is considered as very unlikely since in the oral study the administration of dose levels","page":25,"pdf":"sccp_o_078.pdf","row_type":"noael_study","study_id":"sccp_o_078_noael_020"}
SCCS_vision_codex	NOAEL	=411	mg/kg bw/day	rat	oral	90d	repeated dose toxicity	{"dose":"Therefore, according to the submission, the oral NOAEL corresponds to 411 mg/kg bw/day.","effect":"SCCS-rejected applicant NOAEL: ether with some effects on the identified target organs being the kidney and the liver. These effects were partly associated with changes in clinical chemistry. Very often the most susceptible parameter was the increase in liver weight. The latter, however, without any histopathological correlate, is not considered by the submission authors to reflect an adverse effect per se but should be considered as an adaptive metabolic response which is known to be reversible. Therefore, according to the submission, the oral NOAEL corresponds to 411 mg/kg bw/day. With regard to the results of the dermal repeated dose studies, a dermal NOAEL of 200 mg/kg bw/day is put forward, on the assumption that deviations without dose-response relationship and without correlated histopathological findings (e.g. the decreased reticulocyte count, increased relative kidney weight, increased platelet count and whole blood cell count in the 90d dermal study in rat) should not be taken into account.","page":35,"pdf":"sccp_o_078.pdf","row_type":"noael_study","study_id":"sccp_o_078_noael_023"}
SCCS_vision_codex	NOAEL	=18	-	-	oral	subchronic	repeated dose toxicity	{"effect":"Unlabeled table on page 18: Finally, the reliable No-Adverse-Effect-Level (NOAEL) for subchronic toxicity after oral","page":18,"pdf":"sccp_o_078.pdf","row_type":"noael_study","study_id":"sccp_o_078_noael_036"}
SCCS_vision_codex	NOAEL	=1980	-	-	-	-	NOAEL study	{"effect":"Unlabeled table on page 19: A number of publications (1980-1992) describe the results of Benzophenone-3 studied in","page":19,"pdf":"sccp_o_078.pdf","row_type":"noael_study","study_id":"sccp_o_078_noael_038"}
SCCS_vision_codex	NOAEL	=36	-	-	-	-	NOAEL study	{"effect":"Unlabeled table on page 19: and a title page [36] to a more extensive description of the materials and methods [73].","page":19,"pdf":"sccp_o_078.pdf","row_type":"noael_study","study_id":"sccp_o_078_noael_039"}
SCCS_vision_codex	NOAEL	=9	-	-	-	-	NOAEL study	{"effect":"Unlabeled table on page 19: bacteria both, with and without metabolic activation (S9 mix from the liver of Aroclor 1254-","page":19,"pdf":"sccp_o_078.pdf","row_type":"noael_study","study_id":"sccp_o_078_noael_040"}
SCCS_vision_codex	NOAEL	=10	%	-	-	-	NOAEL study	{"effect":"Unlabeled table on page 19: prepared immediately prior to use and contained 10% S9. The tested Salmonella","page":19,"pdf":"sccp_o_078.pdf","row_type":"noael_study","study_id":"sccp_o_078_noael_041"}
SCCS_vision_codex	NOAEL	=97	-	-	-	-	NOAEL study	{"effect":"Unlabeled table on page 19: typhimurium strains were combinations of TA97, TA98, TA100, TA1535, TA1537 and/or","page":19,"pdf":"sccp_o_078.pdf","row_type":"noael_study","study_id":"sccp_o_078_noael_042"}
SCCS_vision_codex	NOAEL	=1538	-	-	-	-	NOAEL study	{"effect":"Unlabeled table on page 19: TA1538 and were exposed to the test substance at various concentrations of","page":19,"pdf":"sccp_o_078.pdf","row_type":"noael_study","study_id":"sccp_o_078_noael_043"}
SCCS_vision_codex	NOAEL	=-3	-	-	-	-	NOAEL study	{"effect":"Unlabeled table on page 19: Benzophenone-3 with and without S9 mix. Positive controls were included to demonstrate","page":19,"pdf":"sccp_o_078.pdf","row_type":"noael_study","study_id":"sccp_o_078_noael_044"}
SCCS_vision_codex	NOAEL	=73	-	-	-	-	NOAEL study	{"effect":"Unlabeled table on page 19: Bacteriotoxicity was reported [73] to be observed at a varying degree at and above 333","page":19,"pdf":"sccp_o_078.pdf","row_type":"noael_study","study_id":"sccp_o_078_noael_045"}
SCCS_vision_codex	NOAEL	=1000	-	-	-	-	NOAEL study	{"effect":"Unlabeled table on page 19: µg/plate and at 1000 µg/plate in all tested strains (TA98, TA100, TA1535, TA1537). In that","page":19,"pdf":"sccp_o_078.pdf","row_type":"noael_study","study_id":"sccp_o_078_noael_046"}
SCCS_vision_codex	NOAEL	=30	%	-	-	-	NOAEL study	{"effect":"Unlabeled table on page 19: weak mutagenic response using 30% of S9 hamster mix.","page":19,"pdf":"sccp_o_078.pdf","row_type":"noael_study","study_id":"sccp_o_078_noael_048"}
SCCS_vision_codex	NOAEL	=2	-	-	-	-	NOAEL study	{"effect":"Unlabeled table on page 19: the respective controls, the increase in the numbers of revertants was less than 2-fold","page":19,"pdf":"sccp_o_078.pdf","row_type":"noael_study","study_id":"sccp_o_078_noael_050"}
SCCS_vision_codex	NOAEL	=3	-	-	-	-	NOAEL study	{"effect":"Unlabeled table on page 19: the tested concentration range between 3 and 333 µg/plate. All other studies (not including","page":19,"pdf":"sccp_o_078.pdf","row_type":"noael_study","study_id":"sccp_o_078_noael_052"}
SCCS_vision_codex	NOAEL	=8	-	-	-	-	NOAEL study	{"citation":"Ref.: 8, 30, 36, 73","effect":"Unlabeled table on page 19: Ref.: 8, 30, 36, 73","page":19,"pdf":"sccp_o_078.pdf","row_type":"noael_study","study_id":"sccp_o_078_noael_057"}
SCCS_vision_codex	NOAEL	=1992	-	-	-	-	NOAEL study	{"effect":"Unlabeled table on page 19: A US National Toxicology program report (1992) briefly describes the results of cytogenetic","page":19,"pdf":"sccp_o_078.pdf","row_type":"noael_study","study_id":"sccp_o_078_noael_058"}
SCCS_vision_codex	NOAEL	=5	-	-	-	-	NOAEL study	{"dose":"Unlabeled table on page 19: exchanges (effective dose range 5-50µg/ml) and chromosomal aberrations (20-45µg/ml) in","effect":"Unlabeled table on page 19: exchanges (effective dose range 5-50µg/ml) and chromosomal aberrations (20-45µg/ml) in","page":19,"pdf":"sccp_o_078.pdf","row_type":"noael_study","study_id":"sccp_o_078_noael_060"}
SCCS_vision_codex	NOAEL	=1254	-	rat	-	-	NOAEL study	{"effect":"Unlabeled table on page 19: the presence of Aroclor 1254-induced male Sprague Dawley rat liver S9.","page":19,"pdf":"sccp_o_078.pdf","row_type":"noael_study","study_id":"sccp_o_078_noael_061"}
SCCS_vision_codex	NOAEL	=24	-	-	-	prenatal	developmental toxicity	{"effect":"Unlabeled table on page 24: effect and that the NOAEL for maternal and prenatal developmental toxicity is","page":24,"pdf":"sccp_o_078.pdf","row_type":"noael_study","study_id":"sccp_o_078_noael_066"}
SCCS_vision_codex	NOAEL	=1	-	-	-	-	NOAEL study	{"effect":"Unlabeled table on page 24: Date of study: 01-16 November 2004","page":24,"pdf":"sccp_o_078.pdf","row_type":"noael_study","study_id":"sccp_o_078_noael_069"}
SCCS_vision_codex	NOAEL	=67	-	-	-	-	NOAEL study	{"effect":"Unlabeled table on page 24: Guideline/method: Annex V to Dir. 67/548/EEC, Method B.31; OECD Guideline 414","page":24,"pdf":"sccp_o_078.pdf","row_type":"noael_study","study_id":"sccp_o_078_noael_070"}
SCCS_vision_codex	NOAEL	=25	-	-	-	-	NOAEL study	{"effect":"Unlabeled table on page 24: Group size: 25 mated females per dosage group","page":24,"pdf":"sccp_o_078.pdf","row_type":"noael_study","study_id":"sccp_o_078_noael_071"}
SCCS_vision_codex	NOAEL	=99.8	%	-	-	-	NOAEL study	{"effect":"Unlabeled table on page 24: Purity: 99.8% (GC-FID)","page":24,"pdf":"sccp_o_078.pdf","row_type":"noael_study","study_id":"sccp_o_078_noael_073"}
SCCS_vision_codex	NOAEL	=35	-	-	oral	-	NOAEL study	{"effect":"Unlabeled table on page 35: reversible. Therefore, according to the submission, the oral NOAEL corresponds to","page":35,"pdf":"sccp_o_078.pdf","row_type":"noael_study","study_id":"sccp_o_078_noael_080"}
SCCS_vision_codex	NOAEL	=411	mg/kg bw/day	rat	oral	90d	repeated dose toxicity	{"dose":"Therefore, according to the 2005-submission, the oral NOAEL corresponded to 411 mg/kg bw/day.","effect":"SCCS-rejected applicant NOAEL: ether with effects on the identified target organs being the kidney and the liver. These effects were partly associated with changes in clinical chemistry. Very often the most susceptible parameter was the increase in liver weight. The latter, however, without any histopathological correlate, is not considered by the submission authors to reflect an adverse effect per se but should be considered as an adaptive metabolic response which is known to be reversible. Therefore, according to the 2005-submission, the oral NOAEL corresponded to 411 mg/kg bw/day. With regard to the results of the dermal repeated dose studies, a dermal NOAEL of 200 mg/kg bw/day was put forward, on the assumption that deviations without dose-response relationship and without correlated histopathological findings (e.g. the decreased reticulocyte count, increased relative kidney weight, increased platelet count and whole blood cell count in the 90d dermal study in rat) should not be taken into account. 8 A teratogenicity study in rat showed BP-3 to be non-ter","page":6,"pdf":"sccp_o_159.pdf","row_type":"noael_study","study_id":"sccp_o_159_noael_001"}
SCCS_vision_codex	NOAEL	=200	mg/kg bw/day	rat	oral	90d	repeated dose toxicity	{"dose":"Therefore, according to the 2005-submission, the oral NOAEL corresponded to 411 mg/kg bw/day.","effect":"SCCS-rejected applicant NOAEL: ciated with changes in clinical chemistry. Very often the most susceptible parameter was the increase in liver weight. The latter, however, without any histopathological correlate, is not considered by the submission authors to reflect an adverse effect per se but should be considered as an adaptive metabolic response which is known to be reversible. Therefore, according to the 2005-submission, the oral NOAEL corresponded to 411 mg/kg bw/day. With regard to the results of the dermal repeated dose studies, a dermal NOAEL of 200 mg/kg bw/day was put forward, on the assumption that deviations without dose-response relationship and without correlated histopathological findings (e.g. the decreased reticulocyte count, increased relative kidney weight, increased platelet count and whole blood cell count in the 90d dermal study in rat) should not be taken into account. 8 A teratogenicity study in rat showed BP-3 to be non-teratogenic under the conditions of the test. Only at the highest dosage level, which also caused maternal toxicity,","page":6,"pdf":"sccp_o_159.pdf","row_type":"noael_study","study_id":"sccp_o_159_noael_002"}
SCCS_vision_codex	NOAEL	=1.78	mg/kg bw/day	rat	dermal	-	dermal absorption	{"dose":"9.9% [mean (3.1%) + 2 SD (2*3.4%)] Applied dose (sunscreen):","effect":"SCCP/1201/08 Opinion on benzophenone-3 13 3.2.4 Safety evaluation (including calculation of the MoS) BP-3 as a UV-filter in sunscreens up to 6% Dermal absorption (6% formulation): 9.9% [mean (3.1%) + 2 SD (2*3.4%)] Applied dose (sunscreen): 18 g/day Typical human body weight: 60 kg No observed effect level NOAEL (terato-rat): 200 mg/kg bw/day Systemic exposure dose (SED) = (18.103 mg/day * 6/100 * 9.9/100) / 60 kg = 1.78 mg/kg bw/day MoS = NOAEL / SED = 112 BP-3 as a UV-filter at 0.5% to protect cosmetic formulations against sunlight Dermal absorption (2% formulation): 8.0% [mean (4.0%) + 2 SD (2*2.0%)] Applied dose (all cosmetic products): 17.79 g/day Typical human body weight: 60 kg No observed effect level NOAEL (terato-rat): 200 mg/kg bw/day Systemic exposure dose (SED) = (17.79.103 mg/day * 0.5/100 * 8.0/100) / 60 kg = 0.119 mg/kg bw/day MoS = NOAEL / SED = 1686 3.2.5 Discussion A detailed discussion on the general toxicological profile of B","page":13,"pdf":"sccp_o_159.pdf","row_type":"noael_study","study_id":"sccp_o_159_noael_005"}
SCCS_vision_codex	NOAEL	=0.119	mg/kg bw/day	rat	dermal	-	dermal absorption	{"dose":"temic exposure dose (SED) = (18.103 mg/day * 6/100 * 9.9/100) / 60 kg = 1.78 mg/kg bw/day MoS = NOAEL / SED = 112 BP-3 as a UV-filter at 0.5% to protect cosmetic formulations against sunlight Dermal absorption (2% formulation):","effect":"temic exposure dose (SED) = (18.103 mg/day * 6/100 * 9.9/100) / 60 kg = 1.78 mg/kg bw/day MoS = NOAEL / SED = 112 BP-3 as a UV-filter at 0.5% to protect cosmetic formulations against sunlight Dermal absorption (2% formulation): 8.0% [mean (4.0%) + 2 SD (2*2.0%)] Applied dose (all cosmetic products): 17.79 g/day Typical human body weight: 60 kg No observed effect level NOAEL (terato-rat): 200 mg/kg bw/day Systemic exposure dose (SED) = (17.79.103 mg/day * 0.5/100 * 8.0/100) / 60 kg = 0.119 mg/kg bw/day MoS = NOAEL / SED = 1686 3.2.5 Discussion A detailed discussion on the general toxicological profile of BP-3 was given in SCCP/1069/06 and taken over under section 3.1 of the current opinion. The major shortcoming in the dossier was the absence of a sound dermal absorption study, allowing the calculation of the Margin of Safety for the UV-filter. The newly provided in vitro dermal absorption study is considered scientifically acceptable and shows a mean dermal absorption level of 19.3 µg/cm² or 3.1% of the applied dose fo","page":13,"pdf":"sccp_o_159.pdf","row_type":"noael_study","study_id":"sccp_o_159_noael_007"}
SCCS_vision_codex	NOAEL	=6	-	-	oral	-	NOAEL study	{"effect":"Unlabeled table on page 6: reversible. Therefore, according to the 2005-submission, the oral NOAEL corresponded to","page":6,"pdf":"sccp_o_159.pdf","row_type":"noael_study","study_id":"sccp_o_159_noael_009"}
SCCS_vision_codex	NOAEL	=7	-	-	-	developmental	developmental toxicity	{"effect":"Unlabeled table on page 7: skeletal aberrations were noted. The NOAEL-value for maternal and developmental","page":7,"pdf":"sccp_o_159.pdf","row_type":"noael_study","study_id":"sccp_o_159_noael_011"}
SCCS_vision_codex	NOAEL	=56	-	-	-	-	NOAEL study	{"effect":"Unlabeled table on page 7: (cid:56) Toxicokinetic studies indicated that BP-3 was readily biotransformed into its three major","page":7,"pdf":"sccp_o_159.pdf","row_type":"noael_study","study_id":"sccp_o_159_noael_013"}
SCCS_vision_codex	NOAEL	=-3	-	-	-	-	NOAEL study	{"effect":"Unlabeled table on page 7: The SCCP was unable to calculate the Margin of Safety for BP-3 as no scientifically","page":7,"pdf":"sccp_o_159.pdf","row_type":"noael_study","study_id":"sccp_o_159_noael_015"}
SCCS_vision_codex	NOAEL	=3.2	-	-	-	-	NOAEL study	{"effect":"Unlabeled table on page 7: 3.2 DATA INTRODUCED","page":7,"pdf":"sccp_o_159.pdf","row_type":"noael_study","study_id":"sccp_o_159_noael_016"}
SCCS_vision_codex	NOAEL	=13	-	rat	-	-	NOAEL study	{"effect":"Unlabeled table on page 13: The available teratogenicity study in the rat generated a NOAEL-value for maternal and","page":13,"pdf":"sccp_o_159.pdf","row_type":"noael_study","study_id":"sccp_o_159_noael_017"}
SCCS_vision_codex	NOAEL	=19.3	µg/cm	-	dermal	-	dermal absorption	{"dose":"Unlabeled table on page 13: and shows a mean dermal absorption level of 19.3 µg/cm² or 3.1% of the applied dose for a","effect":"Unlabeled table on page 13: and shows a mean dermal absorption level of 19.3 µg/cm² or 3.1% of the applied dose for a","page":13,"pdf":"sccp_o_159.pdf","row_type":"noael_study","study_id":"sccp_o_159_noael_018"}
SCCS_vision_codex	NOAEL	=6	%	-	-	-	NOAEL study	{"effect":"Unlabeled table on page 13: sunscreen (o/w or w/o) containing the maximum requested BP-3 concentration of 6%.","page":13,"pdf":"sccp_o_159.pdf","row_type":"noael_study","study_id":"sccp_o_159_noael_019"}
SCCS_vision_codex	NOAEL	=0.5	%	-	-	-	NOAEL study	{"effect":"Unlabeled table on page 13: protect formulations up to 0.5% in all types of cosmetics), the MoS of BP-3 is above 100.","page":13,"pdf":"sccp_o_159.pdf","row_type":"noael_study","study_id":"sccp_o_159_noael_023"}
SCCS_vision_codex	NOAEL	=411	mg/kg bw/day	rat	oral	90d	repeated dose toxicity	{"dose":"Therefore, according to the 2005-submission, the oral NOAEL corresponded to 411 mg/kg bw/day.","effect":"SCCS-rejected applicant NOAEL: ether with effects on the identified target organs being the kidney and the liver. These effects were partly associated with changes in clinical chemistry. Very often the most susceptible parameter was the increase in liver weight. The latter, however, without any histopathological correlate, is not considered by the submission authors to reflect an adverse effect per se but should be considered as an adaptive metabolic response which is known to be reversible. Therefore, according to the 2005-submission, the oral NOAEL corresponded to 411 mg/kg bw/day. With regard to the results of the dermal repeated dose studies, a dermal NOAEL of 200 mg/kg bw/day was put forward, on the assumption that deviations without dose-response relationship and without correlated histopathological findings (e.g. the decreased reticulocyte count, increased relative kidney weight, increased platelet count and whole blood cell count in the 90d dermal study in rat) should not be taken into account. 8 A teratogenicity study in rat showed BP-3 to be non-ter","page":6,"pdf":"sccp_o_159.pdf","row_type":"noael_study","study_id":"sccp_o_159_noael_001"}
SCCS_vision_codex	NOAEL	=200	mg/kg bw/day	rat	oral	90d	repeated dose toxicity	{"dose":"Therefore, according to the 2005-submission, the oral NOAEL corresponded to 411 mg/kg bw/day.","effect":"SCCS-rejected applicant NOAEL: ciated with changes in clinical chemistry. Very often the most susceptible parameter was the increase in liver weight. The latter, however, without any histopathological correlate, is not considered by the submission authors to reflect an adverse effect per se but should be considered as an adaptive metabolic response which is known to be reversible. Therefore, according to the 2005-submission, the oral NOAEL corresponded to 411 mg/kg bw/day. With regard to the results of the dermal repeated dose studies, a dermal NOAEL of 200 mg/kg bw/day was put forward, on the assumption that deviations without dose-response relationship and without correlated histopathological findings (e.g. the decreased reticulocyte count, increased relative kidney weight, increased platelet count and whole blood cell count in the 90d dermal study in rat) should not be taken into account. 8 A teratogenicity study in rat showed BP-3 to be non-teratogenic under the conditions of the test. Only at the highest dosage level, which also caused maternal toxicity,","page":6,"pdf":"sccp_o_159.pdf","row_type":"noael_study","study_id":"sccp_o_159_noael_002"}
SCCS_vision_codex	NOAEL	=1.78	mg/kg bw/day	rat	dermal	-	dermal absorption	{"dose":"9.9% [mean (3.1%) + 2 SD (2*3.4%)] Applied dose (sunscreen):","effect":"SCCP/1201/08 Opinion on benzophenone-3 13 3.2.4 Safety evaluation (including calculation of the MoS) BP-3 as a UV-filter in sunscreens up to 6% Dermal absorption (6% formulation): 9.9% [mean (3.1%) + 2 SD (2*3.4%)] Applied dose (sunscreen): 18 g/day Typical human body weight: 60 kg No observed effect level NOAEL (terato-rat): 200 mg/kg bw/day Systemic exposure dose (SED) = (18.103 mg/day * 6/100 * 9.9/100) / 60 kg = 1.78 mg/kg bw/day MoS = NOAEL / SED = 112 BP-3 as a UV-filter at 0.5% to protect cosmetic formulations against sunlight Dermal absorption (2% formulation): 8.0% [mean (4.0%) + 2 SD (2*2.0%)] Applied dose (all cosmetic products): 17.79 g/day Typical human body weight: 60 kg No observed effect level NOAEL (terato-rat): 200 mg/kg bw/day Systemic exposure dose (SED) = (17.79.103 mg/day * 0.5/100 * 8.0/100) / 60 kg = 0.119 mg/kg bw/day MoS = NOAEL / SED = 1686 3.2.5 Discussion A detailed discussion on the general toxicological profile of B","page":13,"pdf":"sccp_o_159.pdf","row_type":"noael_study","study_id":"sccp_o_159_noael_005"}
SCCS_vision_codex	NOAEL	=0.119	mg/kg bw/day	rat	dermal	-	dermal absorption	{"dose":"temic exposure dose (SED) = (18.103 mg/day * 6/100 * 9.9/100) / 60 kg = 1.78 mg/kg bw/day MoS = NOAEL / SED = 112 BP-3 as a UV-filter at 0.5% to protect cosmetic formulations against sunlight Dermal absorption (2% formulation):","effect":"temic exposure dose (SED) = (18.103 mg/day * 6/100 * 9.9/100) / 60 kg = 1.78 mg/kg bw/day MoS = NOAEL / SED = 112 BP-3 as a UV-filter at 0.5% to protect cosmetic formulations against sunlight Dermal absorption (2% formulation): 8.0% [mean (4.0%) + 2 SD (2*2.0%)] Applied dose (all cosmetic products): 17.79 g/day Typical human body weight: 60 kg No observed effect level NOAEL (terato-rat): 200 mg/kg bw/day Systemic exposure dose (SED) = (17.79.103 mg/day * 0.5/100 * 8.0/100) / 60 kg = 0.119 mg/kg bw/day MoS = NOAEL / SED = 1686 3.2.5 Discussion A detailed discussion on the general toxicological profile of BP-3 was given in SCCP/1069/06 and taken over under section 3.1 of the current opinion. The major shortcoming in the dossier was the absence of a sound dermal absorption study, allowing the calculation of the Margin of Safety for the UV-filter. The newly provided in vitro dermal absorption study is considered scientifically acceptable and shows a mean dermal absorption level of 19.3 µg/cm² or 3.1% of the applied dose fo","page":13,"pdf":"sccp_o_159.pdf","row_type":"noael_study","study_id":"sccp_o_159_noael_007"}
SCCS_vision_codex	NOAEL	=6	-	-	oral	-	NOAEL study	{"effect":"Unlabeled table on page 6: reversible. Therefore, according to the 2005-submission, the oral NOAEL corresponded to","page":6,"pdf":"sccp_o_159.pdf","row_type":"noael_study","study_id":"sccp_o_159_noael_009"}
SCCS_vision_codex	NOAEL	=7	-	-	-	developmental	developmental toxicity	{"effect":"Unlabeled table on page 7: skeletal aberrations were noted. The NOAEL-value for maternal and developmental","page":7,"pdf":"sccp_o_159.pdf","row_type":"noael_study","study_id":"sccp_o_159_noael_011"}
SCCS_vision_codex	NOAEL	=56	-	-	-	-	NOAEL study	{"effect":"Unlabeled table on page 7: (cid:56) Toxicokinetic studies indicated that BP-3 was readily biotransformed into its three major","page":7,"pdf":"sccp_o_159.pdf","row_type":"noael_study","study_id":"sccp_o_159_noael_013"}
SCCS_vision_codex	NOAEL	=-3	-	-	-	-	NOAEL study	{"effect":"Unlabeled table on page 7: The SCCP was unable to calculate the Margin of Safety for BP-3 as no scientifically","page":7,"pdf":"sccp_o_159.pdf","row_type":"noael_study","study_id":"sccp_o_159_noael_015"}
SCCS_vision_codex	NOAEL	=3.2	-	-	-	-	NOAEL study	{"effect":"Unlabeled table on page 7: 3.2 DATA INTRODUCED","page":7,"pdf":"sccp_o_159.pdf","row_type":"noael_study","study_id":"sccp_o_159_noael_016"}
SCCS_vision_codex	NOAEL	=13	-	rat	-	-	NOAEL study	{"effect":"Unlabeled table on page 13: The available teratogenicity study in the rat generated a NOAEL-value for maternal and","page":13,"pdf":"sccp_o_159.pdf","row_type":"noael_study","study_id":"sccp_o_159_noael_017"}
SCCS_vision_codex	NOAEL	=19.3	µg/cm	-	dermal	-	dermal absorption	{"dose":"Unlabeled table on page 13: and shows a mean dermal absorption level of 19.3 µg/cm² or 3.1% of the applied dose for a","effect":"Unlabeled table on page 13: and shows a mean dermal absorption level of 19.3 µg/cm² or 3.1% of the applied dose for a","page":13,"pdf":"sccp_o_159.pdf","row_type":"noael_study","study_id":"sccp_o_159_noael_018"}
SCCS_vision_codex	NOAEL	=6	%	-	-	-	NOAEL study	{"effect":"Unlabeled table on page 13: sunscreen (o/w or w/o) containing the maximum requested BP-3 concentration of 6%.","page":13,"pdf":"sccp_o_159.pdf","row_type":"noael_study","study_id":"sccp_o_159_noael_019"}
SCCS_vision_codex	NOAEL	=0.5	%	-	-	-	NOAEL study	{"effect":"Unlabeled table on page 13: protect formulations up to 0.5% in all types of cosmetics), the MoS of BP-3 is above 100.","page":13,"pdf":"sccp_o_159.pdf","row_type":"noael_study","study_id":"sccp_o_159_noael_023"}
SCCS_vision_codex	NOAEL	=411	mg/kg bw/day	rat	oral	90d	repeated dose toxicity	{"dose":"Therefore, according to the 2005- submission, the oral NOAEL corresponded to 411 mg/kg bw/day.","effect":"SCCS-rejected applicant NOAEL: ther with effects on the identified target organs being the kidney and the liver. These effects were partly associated with changes in clinical chemistry. Very often the most susceptible parameter was the increase in liver weight. The latter, however, without any histopathological correlate, is not considered by the submission authors to reflect an adverse effect per se but should be considered as an adaptive metabolic response which is known to be reversible. Therefore, according to the 2005- submission, the oral NOAEL corresponded to 411 mg/kg bw/day. With regard to the results of the dermal repeated dose studies, a dermal NOAEL of 200 mg/kg bw/day was put forward, on the assumption that deviations without dose-response relationship and without correlated histopathological findings (e.g. the decreased reticulocyte count, increased relative kidney weight, increased platelet count and whole blood cell count in the 90d dermal study in rat) should not be taken into account.’ The studies already included in the previous SCCS Opinion","page":25,"pdf":"sccs_o_247.pdf","row_type":"noael_study","study_id":"sccs_o_247_noael_001"}
SCCS_vision_codex	NOAEL	=200	mg/kg bw/day	rat	oral	90d	repeated dose toxicity	{"dose":"Therefore, according to the 2005- submission, the oral NOAEL corresponded to 411 mg/kg bw/day.","effect":"SCCS-rejected applicant NOAEL: iated with changes in clinical chemistry. Very often the most susceptible parameter was the increase in liver weight. The latter, however, without any histopathological correlate, is not considered by the submission authors to reflect an adverse effect per se but should be considered as an adaptive metabolic response which is known to be reversible. Therefore, according to the 2005- submission, the oral NOAEL corresponded to 411 mg/kg bw/day. With regard to the results of the dermal repeated dose studies, a dermal NOAEL of 200 mg/kg bw/day was put forward, on the assumption that deviations without dose-response relationship and without correlated histopathological findings (e.g. the decreased reticulocyte count, increased relative kidney weight, increased platelet count and whole blood cell count in the 90d dermal study in rat) should not be taken into account.’ The studies already included in the previous SCCS Opinion are not detailed in this Opinion; if they provide information on ED effects, they will be described in the secti","page":25,"pdf":"sccs_o_247.pdf","row_type":"noael_study","study_id":"sccs_o_247_noael_002"}
SCCS_vision_codex	NOAEL	=3000	ppm	-	-	developmental	developmental toxicity	{"dose":"However, on PND 4, pup body weights (male, female, and both) in the 10000 ppm exposure groups were statistically significantly decreased (both sexes approximately 5% lower) compared to the control group.","effect":"ere not statistically significantly different across the exposure groups on PND 1. However, on PND 4, pup body weights (male, female, and both) in the 10000 ppm exposure groups were statistically significantly decreased (both sexes approximately 5% lower) compared to the control group. This response was generally observed over subsequent pre-weaning weights, and by PND 21 combined live pup weight at this dose was 8% lower than control. Conclusion from the applicant Under the conditions of this study, the maternal NOAEL is 3000 ppm (206-478 mg/kg bw/day), based on reduced body weight gain during GD 6–9 and lactation day 4–21. The developmental NOEL is considered as 3000 ppm (206-478 mg/kg bw/day) based on impaired postnatal bodyweight performance at 10000 ppm (660-1609 mg/kg bw/day). (National Toxicology Program, 2020) Guidelines/Guidances: NTP Modified One-Generation study design GLP: FDA GLP","page":27,"pdf":"sccs_o_247.pdf","row_type":"noael_study","study_id":"sccs_o_247_noael_005"}
SCCS_vision_codex	NOAEL	=1000	ppm	-	-	-	NOAEL study	{"dose":"Therefore, a decrease in testosterone, which is significant at 3000 ppm (see Fig 7) supports the plausibility of a decrease in spermatocytes numbers.","effect":"reased in the tubules (see Fig 6); it is known that germinal cells are more sensitive than Sertoli cells to apoptosis (and Sertoli cells are less in numbers in the tubules). Moreover, it is well known that testosterone is needed for meiosis (De Gendt et al., 2004). Therefore, a decrease in testosterone, which is significant at 3000 ppm (see Fig 7) supports the plausibility of a decrease in spermatocytes numbers. Due to the effects on the ↓ of spermatocytes, the SCCS considered 3000 ppm as a LOAEL and therefore the NOAEL is 1000 ppm (67.9 mg /kg bw/day). This value will be used by the SCCS as a point of departure (POD) for the MoS calculation (see section 3.5 safety evaluation)","page":39,"pdf":"sccs_o_247.pdf","row_type":"noael_study","study_id":"sccs_o_247_noael_007"}
SCCS_vision_codex	NOAEL	>99	%	mouse	-	5 weeks	NOAEL study	{"dose":"The lowest dose (30 µg/kg/d) was chosen on the basis of equivalence to the EFSA Tolerable Daily Intake (TDI), whereas 212 µg/kg/d for being close to the 95 percentile reported in human biomonitoring studies in pregnant women, and 3000 µg/kg/d for equivalence to the NOAEL used by EFSA as a point of departure (POD) to derive the TDI.","effect":"housed in polysulfone cages with food (which may have contained phytoestrogens) were exposed orally to BP-3 (>99% purity) from Gestational Day (GD) until the day before weaning (Lactational Day 21 or LD21) at 3 doses of BP-3 (30, 212 and 3000 µg/kg/d). The lowest dose (30 µg/kg/d) was chosen on the basis of equivalence to the EFSA Tolerable Daily Intake (TDI), whereas 212 µg/kg/d for being close to the 95 percentile reported in human biomonitoring studies in pregnant women, and 3000 µg/kg/d for equivalence to the NOAEL used by EFSA as a point of departure (POD) to derive the TDI. The authors noted that doses around 10 times higher are needed in rodents to produce equivalent levels in human urine, which means that the highest dose was still environmentally relevant. The study included 2 negative control groups: 1 vehicle group and a second group of nulliparous female mice, which were housed under the same conditions. At 5 weeks post-weaning (once mammary gland involution was complete), mice were killed and mammary glands (the lef","page":40,"pdf":"sccs_o_247.pdf","row_type":"noael_study","study_id":"sccs_o_247_noael_008"}
SCCS_vision_codex	NOAEL	=67.9	mg/kg bw/d	-	oral	-	NOAEL study	{"dose":"The NOAEL of 67.9 mg/kg bw/d has been derived from Nakamura et al.","effect":"al Opinion Opinion on Benzophenone-3 (CAS No 131-57-7, EC No 205-031-5) _________________________________________________________________________________________________________________ 47 whilst there are indications from some studies to suggest that BP-3 may have endocrine effects, it is not conclusive enough at present to enable deriving a new endocrine-related toxicological point of departure for use in safety assessment. 3.5 SAFETY EVALUATION (INCLUDING CALCULATION OF THE MOS) The SCCS has used the lowest NOAEL values among those obtained from different toxicological endpoints for the calculation of MoS (summarised in Annex-1). The NOAEL of 67.9 mg/kg bw/d has been derived from Nakamura et al. (2015) study. Because of the evidence for rapid and almost complete absorption of BP-3 from the oral route, the SCCS has not applied any adjustment for bioavailability to this NOAEL value. Details of the calculation of systemic exposure dose (SED) are presented in the Tables in Annex-2. The calculation of MoS for different product","page":47,"pdf":"sccs_o_247.pdf","row_type":"noael_study","study_id":"sccs_o_247_noael_009"}
SCCS_vision_codex	NOAEL	=6	%	rat	oral	prenatal	developmental toxicity	{"dose":"Details of the calculation of systemic exposure dose (SED) are presented in the Tables in Annex-2.","effect":"et al. (2015) study. Because of the evidence for rapid and almost complete absorption of BP-3 from the oral route, the SCCS has not applied any adjustment for bioavailability to this NOAEL value. Details of the calculation of systemic exposure dose (SED) are presented in the Tables in Annex-2. The calculation of MoS for different product types are given in Table 3 below: Table 3: Calculation of Margin of Safety for different products containing BP-3 Products Conc. Surface Systemic Exposure Dose (SED) mg/kg bw/d NOAEL* MOS Dermal Inhalation Oral Total UV cream 6% whole body 1.782 0 0 1.782 67.9 38 UV aerosolised spray 6% whole body 1.782 0.105 0 1.887 67.9 36 UV pump spray 6% whole body 1.782 0.001053 0 1.783 67.9 38 UV face cream 6% face 0.152 0 0 0.152 67.9 447 UV hand cream 6% hand 0.214 0 0 0.214 67.9 317 Non-UV** 0.50% whole body 0.116 0 0 0.116 67.9 585 Lipstick 6% lips 0.000 0 0.054 0.054 67.9 1257 * derived from prenatal and postnatal developmental study, oral, rat (Nakamura et al., 2015) ** to protect cosmetic formulat","page":47,"pdf":"sccs_o_247.pdf","row_type":"noael_study","study_id":"sccs_o_247_noael_012"}
SCCS_vision_codex	NOAEL	=1625	-	rat	-	-	NOAEL study	{"effect":"SCCS/1625/20 Final Opinion Opinion on Benzophenone-3 (CAS No 131-57-7, EC No 205-031-5) _________________________________________________________________________________________________________________ 48 were 0. 187 µg/ml in females and 0.238 µg/mL in males. Twenty-four hours after the first application, the median BP-3 levels in plasma were 0.047 µg/ml in females and 0.041 µg/ml in males. This clearly shows that the levels of BP-3 had exceeded the concentration measured in rats at the NOAEL. 3.6 DISCUSSION The 2008 SCCP Opinion (SCCP/1201/08) had noted a number of shortcomings in the data provided as part of the dossier assessed in an earlier Opinion (SCCP/1069/06). Despite this, the SCS agrees with the SCCP Opinion (2008) that the submission provides a reasonably well- structured overview of the available test descriptions and publications. Physicochemical properties BP-3is a widely used UV filter in cosmetic products. It is an off-white to light-yellow powder with a melting point of 62°C to 65°","page":48,"pdf":"sccs_o_247.pdf","row_type":"noael_study","study_id":"sccs_o_247_noael_013"}
SCCS_vision_codex	NOAEL	=1000	mg/kg bw/day	rat	oral	Prenatal	developmental toxicity	{"citation":"Ref: 5, 33 in submission dossier OECD 414 GLP Rat Wistar CrI: WI (Han) Oral Gavage in corn oil 0, 40, 200 and 1000 mg/kg bw/day From GD5 to GD 19 observatio ns at GD 20 25 No adverse ef","dose":"Summary of the available in vivo studies on reproduction function and ED effects of BP-3 Number and reference Species Strain Model Routes Dose, Exposure period Group size Outcomes reported NOAEL/ LOAEL derived by the authors SCCS Comments General toxicity Reprotoxicity Teratogenicity ED related effects - 1- Prenatal developmen tal tox study Stud...","effect":"SCCS/1625/20 Final Opinion Opinion on Benzophenone-3 (CAS No 131-57-7, EC No 205-031-5) _________________________________________________________________________________________________________________ 62 Annex - 1: Summary of the available in vivo studies on reproduction function and ED effects of BP-3 Number and reference Species Strain Model Routes Dose, Exposure period Group size Outcomes reported NOAEL/ LOAEL derived by the authors SCCS Comments General toxicity Reprotoxicity Teratogenicity ED related effects - 1- Prenatal developmen tal tox study Study period: 2004. Ref: 5, 33 in submission dossier OECD 414 GLP Rat Wistar CrI: WI (Han) Oral Gavage in corn oil 0, 40, 200 and 1000 mg/kg bw/day From GD5 to GD 19 observatio ns at GD 20 25 No adverse effects in the dams no significant difference in the number of implantation sites/litter, mean resorptions/litt er, % litters with resorptions, number and weights of","page":62,"pdf":"sccs_o_247.pdf","row_type":"noael_study","study_id":"sccs_o_247_noael_018"}
SCCS_vision_codex	NOAEL	=200	mg/kg bw/d	rat	oral	-	developmental toxicity	{"citation":"Ref: 5, 33 in submission dossier OECD 414 GLP Rat Wistar CrI: WI (Han) Oral Gavage in corn oil 0, 40, 200 and 1000 mg/kg bw/day From GD5 to GD 19 observatio ns at GD 20 25 No adverse ef","dose":"WI (Han) Oral Gavage in corn oil 0, 40, 200 and 1000 mg/kg bw/day From GD5 to GD 19 observatio ns at GD 20 25 No adverse effects in the dams no significant difference in the number of implantation sites/litter, mean resorptions/litt er, % litters with resorptions, number and weights of live fetuses, between the control and treated groups No tera...","effect":"study Study period: 2004. Ref: 5, 33 in submission dossier OECD 414 GLP Rat Wistar CrI: WI (Han) Oral Gavage in corn oil 0, 40, 200 and 1000 mg/kg bw/day From GD5 to GD 19 observatio ns at GD 20 25 No adverse effects in the dams no significant difference in the number of implantation sites/litter, mean resorptions/litt er, % litters with resorptions, number and weights of live fetuses, between the control and treated groups No teratogenic effects Minor disturbance ad delay of ossification at 1000 mg/kg bw/day NOAEL mat. = 200 mg/kg bw/d NOAEL dev. = 200 mg/kg bw/d This study has been used in the previous SCCS opinion as the key study for calculation of the MOS. - 2 - Nakamura et al. 2015 Birth Defects Res 104: 35- 51 Study period: Rat Sprague- Dawley Food , 0, 1000, 3000, 10 000, 25 000, 50 000 ppm, i.e. around 67.9, 207.1, 670.8, 1798.3, 7-8 ↓ body weights of dams at 50 000 ppm at GD 10, 15 and 20; and at 25 000 ppm at GD15 ↓ organ (liver, kidney) weights (absolute no significant difference in the number of implantation si","page":62,"pdf":"sccs_o_247.pdf","row_type":"noael_study","study_id":"sccs_o_247_noael_019"}
SCCS_vision_codex	NOAEL	=0	ppm	-	-	-	reproductive toxicity	{"dose":"i.e. around 67.9, 207.1, 670.8, 1798.3, 7-8 ↓ body weights of dams at 50 000 ppm at GD 10, 15 and 20; and at 25 000 ppm at GD15 ↓ organ (liver, kidney) weights (absolute no significant difference in the number of implantation sites/litter, mean resorptions/litt er, % litters with resorptions, number and weights of live One foetus with hydrocepha...","effect":"i.e. around 67.9, 207.1, 670.8, 1798.3, 7-8 ↓ body weights of dams at 50 000 ppm at GD 10, 15 and 20; and at 25 000 ppm at GD15 ↓ organ (liver, kidney) weights (absolute no significant difference in the number of implantation sites/litter, mean resorptions/litt er, % litters with resorptions, number and weights of live One foetus with hydrocephaly at 50 000 ppm but no other malformations observed In male offspring at PND23: ↓ AGD in male at 50 000 ppm ↓ spermatocytes per seminiferous tubules at 3000 ppm and higher NOAEL : 3 000 ppm (670 mg/kg bw/day LOAEL : 10 000 ppm (1798 mg/kg/d) It would have been useful to have measured foetal testosterone as it is known that a decrease during specific windows of sensitivity in male foetuses mat impaired the development of reproductive","page":62,"pdf":"sccs_o_247.pdf","row_type":"noael_study","study_id":"sccs_o_247_noael_021"}
SCCS_vision_codex	NOAEL	=242	mg/kg bw/d	rat	oral	-	developmental toxicity	{"dose":"2012 (final report in 2015) Equivalent to OECD 414 GLP Rat Sprague- Dawley Oral Food 0, 3000, 10 000 and 30 000, ppm, i.e. around 242, 725 and 3689 mg/kg/ bw/day From GD 5 to GD 15 Observatio n at GD 15 25 .↓ body weights at 10 000 and 30 000 ppm and ↑ food consumption at 30 000 ppm modifications of blood biochemical factors at 30 000 ppm No eff...","effect":"SCCS-rejected applicant NOAEL: y) - 3 - Submission Ref 11 Study period: 2012 (final report in 2015) Equivalent to OECD 414 GLP Rat Sprague- Dawley Oral Food 0, 3000, 10 000 and 30 000, ppm, i.e. around 242, 725 and 3689 mg/kg/ bw/day From GD 5 to GD 15 Observatio n at GD 15 25 .↓ body weights at 10 000 and 30 000 ppm and ↑ food consumption at 30 000 ppm modifications of blood biochemical factors at 30 000 ppm No effects on foetuses, litters No teratogenic effects observed excepted increased skeletal variations not considered treatment related NOAEL mat. = 242 mg/kg bw/d NOAEL dev. = 3689 mg/kg bw/d SCCS agrees with the authors conclusion.","page":63,"pdf":"sccs_o_247.pdf","row_type":"noael_study","study_id":"sccs_o_247_noael_023"}
SCCS_vision_codex	NOAEL	=411	mg/kg/ day	rat	oral	39 days	NOAEL study	{"dose":"om GD6 during 39 days for F0 and then during 105 weeks for F1 Sacrifice at 14 weeks for 10 F1 rats ( m and f) at 0 and 10 000 ppm course of the study ↑ incidence of pigment in bone marrow at 10 000 ppm in m and f ↑ incidence of pigment in spleen at 10 000 ppm in m and f ↑ incidence of syncytial alteration in the liver of males at all doses ↑ inc...","effect":"om GD6 during 39 days for F0 and then during 105 weeks for F1 Sacrifice at 14 weeks for 10 F1 rats ( m and f) at 0 and 10 000 ppm course of the study ↑ incidence of pigment in bone marrow at 10 000 ppm in m and f ↑ incidence of pigment in spleen at 10 000 ppm in m and f ↑ incidence of syncytial alteration in the liver of males at all doses ↑ incidence of renal alterations at 3000 and 10 000 ppm in males ↑ incidence of osseous metaplasia in females at 10 000 ppm - 6 - Rats Oral Food 0, 3125,625,1 in males: NOAEL = 411 mg/kg/ day","page":65,"pdf":"sccs_o_247.pdf","row_type":"noael_study","study_id":"sccs_o_247_noael_028"}
SCCS_vision_codex	NOAEL	=100	mg/kg bw/day	rat	oral	Sub-chronic	repeated dose toxicity	{"dose":"at 3458 mg/kg bw/day In females: ↑ estrous cycle length in female rats at 3458 mg/kg bw/day based on effects in the kidney - 7 - Ref 7, 16, 33 in submission dossier Sub-chronic toxicity study OECD 408 Non GLP Rats Oral Food 0, 0, 0.02, 0.1, 0.5 and 1% in the diet ie ± 0, 20, 100, 500 and 1000 mg/kg bw/day 13 weeks In males and females: ↓ in abso...","effect":"at 3458 mg/kg bw/day In females: ↑ estrous cycle length in female rats at 3458 mg/kg bw/day based on effects in the kidney - 7 - Ref 7, 16, 33 in submission dossier Sub-chronic toxicity study OECD 408 Non GLP Rats Oral Food 0, 0, 0.02, 0.1, 0.5 and 1% in the diet ie ± 0, 20, 100, 500 and 1000 mg/kg bw/day 13 weeks In males and females: ↓ in absolute weights of adrenal gland, pituitary gland and gonads at 1000 mg/kg bw/day ↑ in relative thyroid and pituitary and adrenal weights at 500 and 1000 mg/kg bw/day NOAEL = 100 mg/kg bw/day","page":66,"pdf":"sccs_o_247.pdf","row_type":"noael_study","study_id":"sccs_o_247_noael_029"}
SCCS_vision_codex	NOAEL	=1246	mg/kg bw /day	rat	oral	Sub-chronic	repeated dose toxicity	{"dose":"___________________________________________________________________________________________________ 67 - 8 - Ref 5, 7, 33 in submission dossier Sub-chronic toxicity study OECD 408 GLP Mice Oral Food 0, 3125,6250, 12500, 25000 and 50000 ppm , ie ± 0, 554, 1246, 2860, 6780 and 16238 mg/kg bw/day 13 weeks No effects on reproductive parameters at 67...","effect":"___________________________________________________________________________________________________ 67 - 8 - Ref 5, 7, 33 in submission dossier Sub-chronic toxicity study OECD 408 GLP Mice Oral Food 0, 3125,6250, 12500, 25000 and 50000 ppm , ie ± 0, 554, 1246, 2860, 6780 and 16238 mg/kg bw/day 13 weeks No effects on reproductive parameters at 6780 mg/kg bw/day or below Males: ↓ in sperm density and ↑ in abnormal sperm morphology at 16238 mg/kg bw/day Females: ↑ in estrous cycles length at 16238 mg/kg bw/day NOAEL = 1246 mg/kg bw /day based on systemic effects -9- Ref 21 Sub-chronic toxicity study GLP Rats 0 and 10000 ppm ie ± 585/632 mg/kg bw/day in males and females Estrogen- responsive genes showed no change in response to BP- 3 in transcriptome analysis -10- Ref 5, 7, 33 in submission dossier Sub-chronic toxicity study ± OECD 411 GLP Rats Dermal 0, 12.5, 25, 50, 100 and 200 mg/kg bw/day 13 weeks No effects on reproductive parameters NOAEL = 200 mg/kg bw/day -11- Mice Dermal 0, 22.8, 45.5, 91, ↓ in epi","page":67,"pdf":"sccs_o_247.pdf","row_type":"noael_study","study_id":"sccs_o_247_noael_030"}
SCCS_vision_codex	NOAEL	=364	mg/kg bw/day	rat	dermal	Sub-chronic	repeated dose toxicity	{"dose":"based on systemic effects -9- Ref 21 Sub-chronic toxicity study GLP Rats 0 and 10000 ppm ie ± 585/632 mg/kg bw/day in males and females Estrogen- responsive genes showed no change in response to BP- 3 in transcriptome analysis -10- Ref 5, 7, 33 in submission dossier Sub-chronic toxicity study ± OECD 411 GLP Rats Dermal 0, 12.5, 25, 50, 100 and 2...","effect":"based on systemic effects -9- Ref 21 Sub-chronic toxicity study GLP Rats 0 and 10000 ppm ie ± 585/632 mg/kg bw/day in males and females Estrogen- responsive genes showed no change in response to BP- 3 in transcriptome analysis -10- Ref 5, 7, 33 in submission dossier Sub-chronic toxicity study ± OECD 411 GLP Rats Dermal 0, 12.5, 25, 50, 100 and 200 mg/kg bw/day 13 weeks No effects on reproductive parameters NOAEL = 200 mg/kg bw/day -11- Mice Dermal 0, 22.8, 45.5, 91, ↓ in epididymal sperm density NOAEL = 364 mg/kg bw/day In view of the effects on sperm","page":67,"pdf":"sccs_o_247.pdf","row_type":"noael_study","study_id":"sccs_o_247_noael_032"}
SCCS_vision_codex	NOAEL	=3	-	-	-	-	NOAEL study	{"dose":"Products | Conc. | Surface | Systemic Exposure Dose (SED) mg/kg bw/d | NOAEL* | MOS","effect":"Table 3: Calculation of Margin of Safety for different products containing BP-3: Products | Conc. | Surface | Systemic Exposure Dose (SED) mg/kg bw/d | NOAEL* | MOS","page":47,"pdf":"sccs_o_247.pdf","row_type":"noael_study","study_id":"sccs_o_247_noael_033"}
SCCS_vision_codex	NOAEL	=0.5	%	-	-	-	NOAEL study	{"effect":"Table 3: Calculation of Margin of Safety for different products containing BP-3: Non-UV** | 0.50% | whole body | 0.116 | 0 | 0 | 0.116 | 67.9 | 585","page":47,"pdf":"sccs_o_247.pdf","row_type":"noael_study","study_id":"sccs_o_247_noael_039"}
SCCS_vision_codex	NOAEL	=62	-	-	-	-	NOAEL study	{"dose":"Number and reference | Species Strain Model | Routes | Dose, Exposure period | Group size | Outcomes reported | NOAEL/ LOAEL derived by the authors | SCCS Comments","effect":"Unlabeled table on page 62: Number and reference | Species Strain Model | Routes | Dose, Exposure period | Group size | Outcomes reported | NOAEL/ LOAEL derived by the authors | SCCS Comments","page":62,"pdf":"sccs_o_247.pdf","row_type":"noael_study","study_id":"sccs_o_247_noael_041"}
SCCS_vision_codex	NOAEL	=3448.2	mg/kg/day	-	-	-	NOAEL study	{"dose":"Unlabeled table on page 63: and 3448.2 mg/kg/day . from GD6 to PND 23 Observatio n on PND1 and PND 23 | and relative) in female and male offspring and blood biochemical factors in the high dose (≥10,000 ppm) groups | fetuses, or sex ratios between the control and treated groups; ↑ ovaries and uterine weights (absolute and relative) at 1000 ppm b...","effect":"Unlabeled table on page 63: and 3448.2 mg/kg/day . from GD6 to PND 23 Observatio n on PND1 and PND 23 | and relative) in female and male offspring and blood biochemical factors in the high dose (≥10,000 ppm) groups | fetuses, or sex ratios between the control and treated groups; ↑ ovaries and uterine weights (absolute and relative) at 1000 ppm but not at higher doses | doses (dose related) ↑ apoptic cells in seminiferous tubules at 10 000 ppm and above (not dose related) Limited ↓ testo level at 3000 and 25 000 ppm In female offspring at PND23 Delayed follicular development at 10 000 and 50 000 ppm | system (↓ AGD, ↓ spermatocytes production and/or quality…) Due to the effects on the ↓ of spermatocyte which may be due to an ED effects of BP-3 SCCS considered 3000 ppm as a LOAEL and therefore the NOAEL should be 1000 ppm ( 68 mg /kg bw/day)","page":63,"pdf":"sccs_o_247.pdf","row_type":"noael_study","study_id":"sccs_o_247_noael_045"}
SCCS_vision_codex	NOAEL	=3689	mg/kg	rat	oral	-	developmental toxicity	{"dose":"2012 (final report in 2015) Equivalent to OECD 414 GLP | Rat Sprague- Dawley | Oral Food | 0, 3000, 10 000 and 30 000, ppm, i.e. around 242, 725 and 3689 mg/kg/ bw/day From GD 5 to GD 15 Observatio n at GD 15 | 25 | .↓ body weights at 10 000 and 30 000 ppm and ↑ food consumption at 30 000 ppm modifications of blood biochemical factors at 30 000...","effect":"SCCS-rejected applicant NOAEL: Unlabeled table on page 63: - 3 - Submission Ref 11 Study period: 2012 (final report in 2015) Equivalent to OECD 414 GLP | Rat Sprague- Dawley | Oral Food | 0, 3000, 10 000 and 30 000, ppm, i.e. around 242, 725 and 3689 mg/kg/ bw/day From GD 5 to GD 15 Observatio n at GD 15 | 25 | .↓ body weights at 10 000 and 30 000 ppm and ↑ food consumption at 30 000 ppm modifications of blood biochemical factors at 30 000 ppm | No effects on foetuses, litters | No teratogenic effects observed excepted increased skeletal variations not considered treatment related | NOAEL mat. = 242 mg/kg bw/d NOAEL dev. = 3689 mg/kg bw/d | SCCS agrees with the authors conclusion.","page":63,"pdf":"sccs_o_247.pdf","row_type":"noael_study","study_id":"sccs_o_247_noael_046"}
SCCS_vision_codex	NOAEL	=660	mg/kg	rat	oral	105 weeks	developmental toxicity	{"dose":"2010-2012 (final report in 2020) Ref 21 in submission dossier GLP | Rat Sprague- Dawley | Oral Food | 0,1000,300 0and 10 000, ppm, i.e. ± 70, 206 and 660 mg/kg/ bw/day during gestation and 157, 478 and 1609 mg/kg bw/day during lactation . from GD6 until PND 21 for F0 and then during 105 weeks for F1 observatio n at PND1, 4, 7 , 14 and 21 | 35-42...","effect":"Unlabeled table on page 64: - 4 - NTP modified 1- gen study equivalent to perinatal developmen tal tox study Study period : 2010-2012 (final report in 2020) Ref 21 in submission dossier GLP | Rat Sprague- Dawley | Oral Food | 0,1000,300 0and 10 000, ppm, i.e. ± 70, 206 and 660 mg/kg/ bw/day during gestation and 157, 478 and 1609 mg/kg bw/day during lactation . from GD6 until PND 21 for F0 and then during 105 weeks for F1 observatio n at PND1, 4, 7 , 14 and 21 | 35-42 femal es for F0 and 50-60 for F1 (m and f) | At 10 000 ppm: ↓ body weights gain in F0 at GD6- 9 and lactation day 4-21 At 3000 ppm: ↓ body weights gain in F0 at GD 18 -21 ↓ body weights of F1 m and f at 10 000 ppm over the course of the study and at 3000 ppm in f at week 77 | No effects on number of pups, litter size, sex distribution, In female F1: ↑ stromal polyp and endometrium hyperplasia ppm in the uterus at 3000 In male F1: ↑ fibirnoid necrosis of the arterioles at 10 000 ppm at the end of the 2 years | No teratogenic effects except at the highest dose: skeletal aberrations in the presence of maternal toxicity |...","page":64,"pdf":"sccs_o_247.pdf","row_type":"noael_study","study_id":"sccs_o_247_noael_048"}
SCCS_vision_codex	NOAEL	=1	%	rat	oral	Sub-chronic	repeated dose toxicity	{"dose":"Unlabeled table on page 66: - 7 - Ref 7, 16, 33 in submission dossier Sub-chronic toxicity study OECD 408 Non GLP | Rats | Oral Food | 0, 0, 0.02, 0.1, 0.5 and 1% in the diet ie ± 0, 20, 100, 500 and 1000 mg/kg bw/day 13 weeks | In males and females: ↓ in absolute weights of adrenal gland, pituitary gland and gonads at 1000 mg/kg bw/day ↑ in rel...","effect":"Unlabeled table on page 66: - 7 - Ref 7, 16, 33 in submission dossier Sub-chronic toxicity study OECD 408 Non GLP | Rats | Oral Food | 0, 0, 0.02, 0.1, 0.5 and 1% in the diet ie ± 0, 20, 100, 500 and 1000 mg/kg bw/day 13 weeks | In males and females: ↓ in absolute weights of adrenal gland, pituitary gland and gonads at 1000 mg/kg bw/day ↑ in relative thyroid and pituitary and adrenal weights at 500 and 1000 mg/kg bw/day | NOAEL = 100 mg/kg bw/day","page":66,"pdf":"sccs_o_247.pdf","row_type":"noael_study","study_id":"sccs_o_247_noael_050"}
SCCS_vision_codex	NOAEL	=50000	ppm	mouse	oral	Sub-chronic	repeated dose toxicity	{"dose":"Unlabeled table on page 67: - 8 - Ref 5, 7, 33 in submission dossier Sub-chronic toxicity study OECD 408 GLP | Mice | Oral Food | 0, 3125,6250, 12500, 25000 and 50000 ppm , ie ± 0, 554, 1246, 2860, 6780 and 16238 mg/kg bw/day 13 weeks | No effects on reproductive parameters at 6780 mg/kg bw/day or below | Males: ↓ in sperm density and ↑ in abnor...","effect":"Unlabeled table on page 67: - 8 - Ref 5, 7, 33 in submission dossier Sub-chronic toxicity study OECD 408 GLP | Mice | Oral Food | 0, 3125,6250, 12500, 25000 and 50000 ppm , ie ± 0, 554, 1246, 2860, 6780 and 16238 mg/kg bw/day 13 weeks | No effects on reproductive parameters at 6780 mg/kg bw/day or below | Males: ↓ in sperm density and ↑ in abnormal sperm morphology at 16238 mg/kg bw/day Females: ↑ in estrous cycles length at 16238 mg/kg bw/day | NOAEL = 1246 mg/kg bw /day based on systemic effects","page":67,"pdf":"sccs_o_247.pdf","row_type":"noael_study","study_id":"sccs_o_247_noael_052"}
SCCS_vision_codex	NOAEL	=411	mg/kg bw/day	rat	oral	90d	repeated dose toxicity	{"dose":"Therefore, according to the 2005- submission, the oral NOAEL corresponded to 411 mg/kg bw/day.","effect":"SCCS-rejected applicant NOAEL: ther with effects on the identified target organs being the kidney and the liver. These effects were partly associated with changes in clinical chemistry. Very often the most susceptible parameter was the increase in liver weight. The latter, however, without any histopathological correlate, is not considered by the submission authors to reflect an adverse effect per se but should be considered as an adaptive metabolic response which is known to be reversible. Therefore, according to the 2005- submission, the oral NOAEL corresponded to 411 mg/kg bw/day. With regard to the results of the dermal repeated dose studies, a dermal NOAEL of 200 mg/kg bw/day was put forward, on the assumption that deviations without dose-response relationship and without correlated histopathological findings (e.g. the decreased reticulocyte count, increased relative kidney weight, increased platelet count and whole blood cell count in the 90d dermal study in rat) should not be taken into account.’ The studies already included in the previous SCCS Opinion","page":25,"pdf":"sccs_o_247.pdf","row_type":"noael_study","study_id":"sccs_o_247_noael_001"}
SCCS_vision_codex	NOAEL	=200	mg/kg bw/day	rat	oral	90d	repeated dose toxicity	{"dose":"Therefore, according to the 2005- submission, the oral NOAEL corresponded to 411 mg/kg bw/day.","effect":"SCCS-rejected applicant NOAEL: iated with changes in clinical chemistry. Very often the most susceptible parameter was the increase in liver weight. The latter, however, without any histopathological correlate, is not considered by the submission authors to reflect an adverse effect per se but should be considered as an adaptive metabolic response which is known to be reversible. Therefore, according to the 2005- submission, the oral NOAEL corresponded to 411 mg/kg bw/day. With regard to the results of the dermal repeated dose studies, a dermal NOAEL of 200 mg/kg bw/day was put forward, on the assumption that deviations without dose-response relationship and without correlated histopathological findings (e.g. the decreased reticulocyte count, increased relative kidney weight, increased platelet count and whole blood cell count in the 90d dermal study in rat) should not be taken into account.’ The studies already included in the previous SCCS Opinion are not detailed in this Opinion; if they provide information on ED effects, they will be described in the secti","page":25,"pdf":"sccs_o_247.pdf","row_type":"noael_study","study_id":"sccs_o_247_noael_002"}
SCCS_vision_codex	NOAEL	=3000	ppm	-	-	developmental	developmental toxicity	{"dose":"However, on PND 4, pup body weights (male, female, and both) in the 10000 ppm exposure groups were statistically significantly decreased (both sexes approximately 5% lower) compared to the control group.","effect":"ere not statistically significantly different across the exposure groups on PND 1. However, on PND 4, pup body weights (male, female, and both) in the 10000 ppm exposure groups were statistically significantly decreased (both sexes approximately 5% lower) compared to the control group. This response was generally observed over subsequent pre-weaning weights, and by PND 21 combined live pup weight at this dose was 8% lower than control. Conclusion from the applicant Under the conditions of this study, the maternal NOAEL is 3000 ppm (206-478 mg/kg bw/day), based on reduced body weight gain during GD 6–9 and lactation day 4–21. The developmental NOEL is considered as 3000 ppm (206-478 mg/kg bw/day) based on impaired postnatal bodyweight performance at 10000 ppm (660-1609 mg/kg bw/day). (National Toxicology Program, 2020) Guidelines/Guidances: NTP Modified One-Generation study design GLP: FDA GLP","page":27,"pdf":"sccs_o_247.pdf","row_type":"noael_study","study_id":"sccs_o_247_noael_005"}
SCCS_vision_codex	NOAEL	=1000	ppm	-	-	-	NOAEL study	{"dose":"Therefore, a decrease in testosterone, which is significant at 3000 ppm (see Fig 7) supports the plausibility of a decrease in spermatocytes numbers.","effect":"reased in the tubules (see Fig 6); it is known that germinal cells are more sensitive than Sertoli cells to apoptosis (and Sertoli cells are less in numbers in the tubules). Moreover, it is well known that testosterone is needed for meiosis (De Gendt et al., 2004). Therefore, a decrease in testosterone, which is significant at 3000 ppm (see Fig 7) supports the plausibility of a decrease in spermatocytes numbers. Due to the effects on the ↓ of spermatocytes, the SCCS considered 3000 ppm as a LOAEL and therefore the NOAEL is 1000 ppm (67.9 mg /kg bw/day). This value will be used by the SCCS as a point of departure (POD) for the MoS calculation (see section 3.5 safety evaluation)","page":39,"pdf":"sccs_o_247.pdf","row_type":"noael_study","study_id":"sccs_o_247_noael_007"}
SCCS_vision_codex	NOAEL	>99	%	mouse	-	5 weeks	NOAEL study	{"dose":"The lowest dose (30 µg/kg/d) was chosen on the basis of equivalence to the EFSA Tolerable Daily Intake (TDI), whereas 212 µg/kg/d for being close to the 95 percentile reported in human biomonitoring studies in pregnant women, and 3000 µg/kg/d for equivalence to the NOAEL used by EFSA as a point of departure (POD) to derive the TDI.","effect":"housed in polysulfone cages with food (which may have contained phytoestrogens) were exposed orally to BP-3 (>99% purity) from Gestational Day (GD) until the day before weaning (Lactational Day 21 or LD21) at 3 doses of BP-3 (30, 212 and 3000 µg/kg/d). The lowest dose (30 µg/kg/d) was chosen on the basis of equivalence to the EFSA Tolerable Daily Intake (TDI), whereas 212 µg/kg/d for being close to the 95 percentile reported in human biomonitoring studies in pregnant women, and 3000 µg/kg/d for equivalence to the NOAEL used by EFSA as a point of departure (POD) to derive the TDI. The authors noted that doses around 10 times higher are needed in rodents to produce equivalent levels in human urine, which means that the highest dose was still environmentally relevant. The study included 2 negative control groups: 1 vehicle group and a second group of nulliparous female mice, which were housed under the same conditions. At 5 weeks post-weaning (once mammary gland involution was complete), mice were killed and mammary glands (the lef","page":40,"pdf":"sccs_o_247.pdf","row_type":"noael_study","study_id":"sccs_o_247_noael_008"}
SCCS_vision_codex	NOAEL	=67.9	mg/kg bw/d	-	oral	-	NOAEL study	{"dose":"The NOAEL of 67.9 mg/kg bw/d has been derived from Nakamura et al.","effect":"al Opinion Opinion on Benzophenone-3 (CAS No 131-57-7, EC No 205-031-5) _________________________________________________________________________________________________________________ 47 whilst there are indications from some studies to suggest that BP-3 may have endocrine effects, it is not conclusive enough at present to enable deriving a new endocrine-related toxicological point of departure for use in safety assessment. 3.5 SAFETY EVALUATION (INCLUDING CALCULATION OF THE MOS) The SCCS has used the lowest NOAEL values among those obtained from different toxicological endpoints for the calculation of MoS (summarised in Annex-1). The NOAEL of 67.9 mg/kg bw/d has been derived from Nakamura et al. (2015) study. Because of the evidence for rapid and almost complete absorption of BP-3 from the oral route, the SCCS has not applied any adjustment for bioavailability to this NOAEL value. Details of the calculation of systemic exposure dose (SED) are presented in the Tables in Annex-2. The calculation of MoS for different product","page":47,"pdf":"sccs_o_247.pdf","row_type":"noael_study","study_id":"sccs_o_247_noael_009"}
SCCS_vision_codex	NOAEL	=6	%	rat	oral	prenatal	developmental toxicity	{"dose":"Details of the calculation of systemic exposure dose (SED) are presented in the Tables in Annex-2.","effect":"et al. (2015) study. Because of the evidence for rapid and almost complete absorption of BP-3 from the oral route, the SCCS has not applied any adjustment for bioavailability to this NOAEL value. Details of the calculation of systemic exposure dose (SED) are presented in the Tables in Annex-2. The calculation of MoS for different product types are given in Table 3 below: Table 3: Calculation of Margin of Safety for different products containing BP-3 Products Conc. Surface Systemic Exposure Dose (SED) mg/kg bw/d NOAEL* MOS Dermal Inhalation Oral Total UV cream 6% whole body 1.782 0 0 1.782 67.9 38 UV aerosolised spray 6% whole body 1.782 0.105 0 1.887 67.9 36 UV pump spray 6% whole body 1.782 0.001053 0 1.783 67.9 38 UV face cream 6% face 0.152 0 0 0.152 67.9 447 UV hand cream 6% hand 0.214 0 0 0.214 67.9 317 Non-UV** 0.50% whole body 0.116 0 0 0.116 67.9 585 Lipstick 6% lips 0.000 0 0.054 0.054 67.9 1257 * derived from prenatal and postnatal developmental study, oral, rat (Nakamura et al., 2015) ** to protect cosmetic formulat","page":47,"pdf":"sccs_o_247.pdf","row_type":"noael_study","study_id":"sccs_o_247_noael_012"}
SCCS_vision_codex	NOAEL	=1625	-	rat	-	-	NOAEL study	{"effect":"SCCS/1625/20 Final Opinion Opinion on Benzophenone-3 (CAS No 131-57-7, EC No 205-031-5) _________________________________________________________________________________________________________________ 48 were 0. 187 µg/ml in females and 0.238 µg/mL in males. Twenty-four hours after the first application, the median BP-3 levels in plasma were 0.047 µg/ml in females and 0.041 µg/ml in males. This clearly shows that the levels of BP-3 had exceeded the concentration measured in rats at the NOAEL. 3.6 DISCUSSION The 2008 SCCP Opinion (SCCP/1201/08) had noted a number of shortcomings in the data provided as part of the dossier assessed in an earlier Opinion (SCCP/1069/06). Despite this, the SCS agrees with the SCCP Opinion (2008) that the submission provides a reasonably well- structured overview of the available test descriptions and publications. Physicochemical properties BP-3is a widely used UV filter in cosmetic products. It is an off-white to light-yellow powder with a melting point of 62°C to 65°","page":48,"pdf":"sccs_o_247.pdf","row_type":"noael_study","study_id":"sccs_o_247_noael_013"}
SCCS_vision_codex	NOAEL	=1000	mg/kg bw/day	rat	oral	Prenatal	developmental toxicity	{"citation":"Ref: 5, 33 in submission dossier OECD 414 GLP Rat Wistar CrI: WI (Han) Oral Gavage in corn oil 0, 40, 200 and 1000 mg/kg bw/day From GD5 to GD 19 observatio ns at GD 20 25 No adverse ef","dose":"Summary of the available in vivo studies on reproduction function and ED effects of BP-3 Number and reference Species Strain Model Routes Dose, Exposure period Group size Outcomes reported NOAEL/ LOAEL derived by the authors SCCS Comments General toxicity Reprotoxicity Teratogenicity ED related effects - 1- Prenatal developmen tal tox study Stud...","effect":"SCCS/1625/20 Final Opinion Opinion on Benzophenone-3 (CAS No 131-57-7, EC No 205-031-5) _________________________________________________________________________________________________________________ 62 Annex - 1: Summary of the available in vivo studies on reproduction function and ED effects of BP-3 Number and reference Species Strain Model Routes Dose, Exposure period Group size Outcomes reported NOAEL/ LOAEL derived by the authors SCCS Comments General toxicity Reprotoxicity Teratogenicity ED related effects - 1- Prenatal developmen tal tox study Study period: 2004. Ref: 5, 33 in submission dossier OECD 414 GLP Rat Wistar CrI: WI (Han) Oral Gavage in corn oil 0, 40, 200 and 1000 mg/kg bw/day From GD5 to GD 19 observatio ns at GD 20 25 No adverse effects in the dams no significant difference in the number of implantation sites/litter, mean resorptions/litt er, % litters with resorptions, number and weights of","page":62,"pdf":"sccs_o_247.pdf","row_type":"noael_study","study_id":"sccs_o_247_noael_018"}
SCCS_vision_codex	NOAEL	=200	mg/kg bw/d	rat	oral	-	developmental toxicity	{"citation":"Ref: 5, 33 in submission dossier OECD 414 GLP Rat Wistar CrI: WI (Han) Oral Gavage in corn oil 0, 40, 200 and 1000 mg/kg bw/day From GD5 to GD 19 observatio ns at GD 20 25 No adverse ef","dose":"WI (Han) Oral Gavage in corn oil 0, 40, 200 and 1000 mg/kg bw/day From GD5 to GD 19 observatio ns at GD 20 25 No adverse effects in the dams no significant difference in the number of implantation sites/litter, mean resorptions/litt er, % litters with resorptions, number and weights of live fetuses, between the control and treated groups No tera...","effect":"study Study period: 2004. Ref: 5, 33 in submission dossier OECD 414 GLP Rat Wistar CrI: WI (Han) Oral Gavage in corn oil 0, 40, 200 and 1000 mg/kg bw/day From GD5 to GD 19 observatio ns at GD 20 25 No adverse effects in the dams no significant difference in the number of implantation sites/litter, mean resorptions/litt er, % litters with resorptions, number and weights of live fetuses, between the control and treated groups No teratogenic effects Minor disturbance ad delay of ossification at 1000 mg/kg bw/day NOAEL mat. = 200 mg/kg bw/d NOAEL dev. = 200 mg/kg bw/d This study has been used in the previous SCCS opinion as the key study for calculation of the MOS. - 2 - Nakamura et al. 2015 Birth Defects Res 104: 35- 51 Study period: Rat Sprague- Dawley Food , 0, 1000, 3000, 10 000, 25 000, 50 000 ppm, i.e. around 67.9, 207.1, 670.8, 1798.3, 7-8 ↓ body weights of dams at 50 000 ppm at GD 10, 15 and 20; and at 25 000 ppm at GD15 ↓ organ (liver, kidney) weights (absolute no significant difference in the number of implantation si","page":62,"pdf":"sccs_o_247.pdf","row_type":"noael_study","study_id":"sccs_o_247_noael_019"}
SCCS_vision_codex	NOAEL	=0	ppm	-	-	-	reproductive toxicity	{"dose":"i.e. around 67.9, 207.1, 670.8, 1798.3, 7-8 ↓ body weights of dams at 50 000 ppm at GD 10, 15 and 20; and at 25 000 ppm at GD15 ↓ organ (liver, kidney) weights (absolute no significant difference in the number of implantation sites/litter, mean resorptions/litt er, % litters with resorptions, number and weights of live One foetus with hydrocepha...","effect":"i.e. around 67.9, 207.1, 670.8, 1798.3, 7-8 ↓ body weights of dams at 50 000 ppm at GD 10, 15 and 20; and at 25 000 ppm at GD15 ↓ organ (liver, kidney) weights (absolute no significant difference in the number of implantation sites/litter, mean resorptions/litt er, % litters with resorptions, number and weights of live One foetus with hydrocephaly at 50 000 ppm but no other malformations observed In male offspring at PND23: ↓ AGD in male at 50 000 ppm ↓ spermatocytes per seminiferous tubules at 3000 ppm and higher NOAEL : 3 000 ppm (670 mg/kg bw/day LOAEL : 10 000 ppm (1798 mg/kg/d) It would have been useful to have measured foetal testosterone as it is known that a decrease during specific windows of sensitivity in male foetuses mat impaired the development of reproductive","page":62,"pdf":"sccs_o_247.pdf","row_type":"noael_study","study_id":"sccs_o_247_noael_021"}
SCCS_vision_codex	NOAEL	=242	mg/kg bw/d	rat	oral	-	developmental toxicity	{"dose":"2012 (final report in 2015) Equivalent to OECD 414 GLP Rat Sprague- Dawley Oral Food 0, 3000, 10 000 and 30 000, ppm, i.e. around 242, 725 and 3689 mg/kg/ bw/day From GD 5 to GD 15 Observatio n at GD 15 25 .↓ body weights at 10 000 and 30 000 ppm and ↑ food consumption at 30 000 ppm modifications of blood biochemical factors at 30 000 ppm No eff...","effect":"SCCS-rejected applicant NOAEL: y) - 3 - Submission Ref 11 Study period: 2012 (final report in 2015) Equivalent to OECD 414 GLP Rat Sprague- Dawley Oral Food 0, 3000, 10 000 and 30 000, ppm, i.e. around 242, 725 and 3689 mg/kg/ bw/day From GD 5 to GD 15 Observatio n at GD 15 25 .↓ body weights at 10 000 and 30 000 ppm and ↑ food consumption at 30 000 ppm modifications of blood biochemical factors at 30 000 ppm No effects on foetuses, litters No teratogenic effects observed excepted increased skeletal variations not considered treatment related NOAEL mat. = 242 mg/kg bw/d NOAEL dev. = 3689 mg/kg bw/d SCCS agrees with the authors conclusion.","page":63,"pdf":"sccs_o_247.pdf","row_type":"noael_study","study_id":"sccs_o_247_noael_023"}
SCCS_vision_codex	NOAEL	=411	mg/kg/ day	rat	oral	39 days	NOAEL study	{"dose":"om GD6 during 39 days for F0 and then during 105 weeks for F1 Sacrifice at 14 weeks for 10 F1 rats ( m and f) at 0 and 10 000 ppm course of the study ↑ incidence of pigment in bone marrow at 10 000 ppm in m and f ↑ incidence of pigment in spleen at 10 000 ppm in m and f ↑ incidence of syncytial alteration in the liver of males at all doses ↑ inc...","effect":"om GD6 during 39 days for F0 and then during 105 weeks for F1 Sacrifice at 14 weeks for 10 F1 rats ( m and f) at 0 and 10 000 ppm course of the study ↑ incidence of pigment in bone marrow at 10 000 ppm in m and f ↑ incidence of pigment in spleen at 10 000 ppm in m and f ↑ incidence of syncytial alteration in the liver of males at all doses ↑ incidence of renal alterations at 3000 and 10 000 ppm in males ↑ incidence of osseous metaplasia in females at 10 000 ppm - 6 - Rats Oral Food 0, 3125,625,1 in males: NOAEL = 411 mg/kg/ day","page":65,"pdf":"sccs_o_247.pdf","row_type":"noael_study","study_id":"sccs_o_247_noael_028"}
SCCS_vision_codex	NOAEL	=100	mg/kg bw/day	rat	oral	Sub-chronic	repeated dose toxicity	{"dose":"at 3458 mg/kg bw/day In females: ↑ estrous cycle length in female rats at 3458 mg/kg bw/day based on effects in the kidney - 7 - Ref 7, 16, 33 in submission dossier Sub-chronic toxicity study OECD 408 Non GLP Rats Oral Food 0, 0, 0.02, 0.1, 0.5 and 1% in the diet ie ± 0, 20, 100, 500 and 1000 mg/kg bw/day 13 weeks In males and females: ↓ in abso...","effect":"at 3458 mg/kg bw/day In females: ↑ estrous cycle length in female rats at 3458 mg/kg bw/day based on effects in the kidney - 7 - Ref 7, 16, 33 in submission dossier Sub-chronic toxicity study OECD 408 Non GLP Rats Oral Food 0, 0, 0.02, 0.1, 0.5 and 1% in the diet ie ± 0, 20, 100, 500 and 1000 mg/kg bw/day 13 weeks In males and females: ↓ in absolute weights of adrenal gland, pituitary gland and gonads at 1000 mg/kg bw/day ↑ in relative thyroid and pituitary and adrenal weights at 500 and 1000 mg/kg bw/day NOAEL = 100 mg/kg bw/day","page":66,"pdf":"sccs_o_247.pdf","row_type":"noael_study","study_id":"sccs_o_247_noael_029"}
SCCS_vision_codex	NOAEL	=1246	mg/kg bw /day	rat	oral	Sub-chronic	repeated dose toxicity	{"dose":"___________________________________________________________________________________________________ 67 - 8 - Ref 5, 7, 33 in submission dossier Sub-chronic toxicity study OECD 408 GLP Mice Oral Food 0, 3125,6250, 12500, 25000 and 50000 ppm , ie ± 0, 554, 1246, 2860, 6780 and 16238 mg/kg bw/day 13 weeks No effects on reproductive parameters at 67...","effect":"___________________________________________________________________________________________________ 67 - 8 - Ref 5, 7, 33 in submission dossier Sub-chronic toxicity study OECD 408 GLP Mice Oral Food 0, 3125,6250, 12500, 25000 and 50000 ppm , ie ± 0, 554, 1246, 2860, 6780 and 16238 mg/kg bw/day 13 weeks No effects on reproductive parameters at 6780 mg/kg bw/day or below Males: ↓ in sperm density and ↑ in abnormal sperm morphology at 16238 mg/kg bw/day Females: ↑ in estrous cycles length at 16238 mg/kg bw/day NOAEL = 1246 mg/kg bw /day based on systemic effects -9- Ref 21 Sub-chronic toxicity study GLP Rats 0 and 10000 ppm ie ± 585/632 mg/kg bw/day in males and females Estrogen- responsive genes showed no change in response to BP- 3 in transcriptome analysis -10- Ref 5, 7, 33 in submission dossier Sub-chronic toxicity study ± OECD 411 GLP Rats Dermal 0, 12.5, 25, 50, 100 and 200 mg/kg bw/day 13 weeks No effects on reproductive parameters NOAEL = 200 mg/kg bw/day -11- Mice Dermal 0, 22.8, 45.5, 91, ↓ in epi","page":67,"pdf":"sccs_o_247.pdf","row_type":"noael_study","study_id":"sccs_o_247_noael_030"}
SCCS_vision_codex	NOAEL	=364	mg/kg bw/day	rat	dermal	Sub-chronic	repeated dose toxicity	{"dose":"based on systemic effects -9- Ref 21 Sub-chronic toxicity study GLP Rats 0 and 10000 ppm ie ± 585/632 mg/kg bw/day in males and females Estrogen- responsive genes showed no change in response to BP- 3 in transcriptome analysis -10- Ref 5, 7, 33 in submission dossier Sub-chronic toxicity study ± OECD 411 GLP Rats Dermal 0, 12.5, 25, 50, 100 and 2...","effect":"based on systemic effects -9- Ref 21 Sub-chronic toxicity study GLP Rats 0 and 10000 ppm ie ± 585/632 mg/kg bw/day in males and females Estrogen- responsive genes showed no change in response to BP- 3 in transcriptome analysis -10- Ref 5, 7, 33 in submission dossier Sub-chronic toxicity study ± OECD 411 GLP Rats Dermal 0, 12.5, 25, 50, 100 and 200 mg/kg bw/day 13 weeks No effects on reproductive parameters NOAEL = 200 mg/kg bw/day -11- Mice Dermal 0, 22.8, 45.5, 91, ↓ in epididymal sperm density NOAEL = 364 mg/kg bw/day In view of the effects on sperm","page":67,"pdf":"sccs_o_247.pdf","row_type":"noael_study","study_id":"sccs_o_247_noael_032"}
SCCS_vision_codex	NOAEL	=3	-	-	-	-	NOAEL study	{"dose":"Products | Conc. | Surface | Systemic Exposure Dose (SED) mg/kg bw/d | NOAEL* | MOS","effect":"Table 3: Calculation of Margin of Safety for different products containing BP-3: Products | Conc. | Surface | Systemic Exposure Dose (SED) mg/kg bw/d | NOAEL* | MOS","page":47,"pdf":"sccs_o_247.pdf","row_type":"noael_study","study_id":"sccs_o_247_noael_033"}
SCCS_vision_codex	NOAEL	=0.5	%	-	-	-	NOAEL study	{"effect":"Table 3: Calculation of Margin of Safety for different products containing BP-3: Non-UV** | 0.50% | whole body | 0.116 | 0 | 0 | 0.116 | 67.9 | 585","page":47,"pdf":"sccs_o_247.pdf","row_type":"noael_study","study_id":"sccs_o_247_noael_039"}
SCCS_vision_codex	NOAEL	=62	-	-	-	-	NOAEL study	{"dose":"Number and reference | Species Strain Model | Routes | Dose, Exposure period | Group size | Outcomes reported | NOAEL/ LOAEL derived by the authors | SCCS Comments","effect":"Unlabeled table on page 62: Number and reference | Species Strain Model | Routes | Dose, Exposure period | Group size | Outcomes reported | NOAEL/ LOAEL derived by the authors | SCCS Comments","page":62,"pdf":"sccs_o_247.pdf","row_type":"noael_study","study_id":"sccs_o_247_noael_041"}
SCCS_vision_codex	NOAEL	=3448.2	mg/kg/day	-	-	-	NOAEL study	{"dose":"Unlabeled table on page 63: and 3448.2 mg/kg/day . from GD6 to PND 23 Observatio n on PND1 and PND 23 | and relative) in female and male offspring and blood biochemical factors in the high dose (≥10,000 ppm) groups | fetuses, or sex ratios between the control and treated groups; ↑ ovaries and uterine weights (absolute and relative) at 1000 ppm b...","effect":"Unlabeled table on page 63: and 3448.2 mg/kg/day . from GD6 to PND 23 Observatio n on PND1 and PND 23 | and relative) in female and male offspring and blood biochemical factors in the high dose (≥10,000 ppm) groups | fetuses, or sex ratios between the control and treated groups; ↑ ovaries and uterine weights (absolute and relative) at 1000 ppm but not at higher doses | doses (dose related) ↑ apoptic cells in seminiferous tubules at 10 000 ppm and above (not dose related) Limited ↓ testo level at 3000 and 25 000 ppm In female offspring at PND23 Delayed follicular development at 10 000 and 50 000 ppm | system (↓ AGD, ↓ spermatocytes production and/or quality…) Due to the effects on the ↓ of spermatocyte which may be due to an ED effects of BP-3 SCCS considered 3000 ppm as a LOAEL and therefore the NOAEL should be 1000 ppm ( 68 mg /kg bw/day)","page":63,"pdf":"sccs_o_247.pdf","row_type":"noael_study","study_id":"sccs_o_247_noael_045"}
SCCS_vision_codex	NOAEL	=3689	mg/kg	rat	oral	-	developmental toxicity	{"dose":"2012 (final report in 2015) Equivalent to OECD 414 GLP | Rat Sprague- Dawley | Oral Food | 0, 3000, 10 000 and 30 000, ppm, i.e. around 242, 725 and 3689 mg/kg/ bw/day From GD 5 to GD 15 Observatio n at GD 15 | 25 | .↓ body weights at 10 000 and 30 000 ppm and ↑ food consumption at 30 000 ppm modifications of blood biochemical factors at 30 000...","effect":"SCCS-rejected applicant NOAEL: Unlabeled table on page 63: - 3 - Submission Ref 11 Study period: 2012 (final report in 2015) Equivalent to OECD 414 GLP | Rat Sprague- Dawley | Oral Food | 0, 3000, 10 000 and 30 000, ppm, i.e. around 242, 725 and 3689 mg/kg/ bw/day From GD 5 to GD 15 Observatio n at GD 15 | 25 | .↓ body weights at 10 000 and 30 000 ppm and ↑ food consumption at 30 000 ppm modifications of blood biochemical factors at 30 000 ppm | No effects on foetuses, litters | No teratogenic effects observed excepted increased skeletal variations not considered treatment related | NOAEL mat. = 242 mg/kg bw/d NOAEL dev. = 3689 mg/kg bw/d | SCCS agrees with the authors conclusion.","page":63,"pdf":"sccs_o_247.pdf","row_type":"noael_study","study_id":"sccs_o_247_noael_046"}
SCCS_vision_codex	NOAEL	=660	mg/kg	rat	oral	105 weeks	developmental toxicity	{"dose":"2010-2012 (final report in 2020) Ref 21 in submission dossier GLP | Rat Sprague- Dawley | Oral Food | 0,1000,300 0and 10 000, ppm, i.e. ± 70, 206 and 660 mg/kg/ bw/day during gestation and 157, 478 and 1609 mg/kg bw/day during lactation . from GD6 until PND 21 for F0 and then during 105 weeks for F1 observatio n at PND1, 4, 7 , 14 and 21 | 35-42...","effect":"Unlabeled table on page 64: - 4 - NTP modified 1- gen study equivalent to perinatal developmen tal tox study Study period : 2010-2012 (final report in 2020) Ref 21 in submission dossier GLP | Rat Sprague- Dawley | Oral Food | 0,1000,300 0and 10 000, ppm, i.e. ± 70, 206 and 660 mg/kg/ bw/day during gestation and 157, 478 and 1609 mg/kg bw/day during lactation . from GD6 until PND 21 for F0 and then during 105 weeks for F1 observatio n at PND1, 4, 7 , 14 and 21 | 35-42 femal es for F0 and 50-60 for F1 (m and f) | At 10 000 ppm: ↓ body weights gain in F0 at GD6- 9 and lactation day 4-21 At 3000 ppm: ↓ body weights gain in F0 at GD 18 -21 ↓ body weights of F1 m and f at 10 000 ppm over the course of the study and at 3000 ppm in f at week 77 | No effects on number of pups, litter size, sex distribution, In female F1: ↑ stromal polyp and endometrium hyperplasia ppm in the uterus at 3000 In male F1: ↑ fibirnoid necrosis of the arterioles at 10 000 ppm at the end of the 2 years | No teratogenic effects except at the highest dose: skeletal aberrations in the presence of maternal toxicity |...","page":64,"pdf":"sccs_o_247.pdf","row_type":"noael_study","study_id":"sccs_o_247_noael_048"}
SCCS_vision_codex	NOAEL	=1	%	rat	oral	Sub-chronic	repeated dose toxicity	{"dose":"Unlabeled table on page 66: - 7 - Ref 7, 16, 33 in submission dossier Sub-chronic toxicity study OECD 408 Non GLP | Rats | Oral Food | 0, 0, 0.02, 0.1, 0.5 and 1% in the diet ie ± 0, 20, 100, 500 and 1000 mg/kg bw/day 13 weeks | In males and females: ↓ in absolute weights of adrenal gland, pituitary gland and gonads at 1000 mg/kg bw/day ↑ in rel...","effect":"Unlabeled table on page 66: - 7 - Ref 7, 16, 33 in submission dossier Sub-chronic toxicity study OECD 408 Non GLP | Rats | Oral Food | 0, 0, 0.02, 0.1, 0.5 and 1% in the diet ie ± 0, 20, 100, 500 and 1000 mg/kg bw/day 13 weeks | In males and females: ↓ in absolute weights of adrenal gland, pituitary gland and gonads at 1000 mg/kg bw/day ↑ in relative thyroid and pituitary and adrenal weights at 500 and 1000 mg/kg bw/day | NOAEL = 100 mg/kg bw/day","page":66,"pdf":"sccs_o_247.pdf","row_type":"noael_study","study_id":"sccs_o_247_noael_050"}
SCCS_vision_codex	NOAEL	=50000	ppm	mouse	oral	Sub-chronic	repeated dose toxicity	{"dose":"Unlabeled table on page 67: - 8 - Ref 5, 7, 33 in submission dossier Sub-chronic toxicity study OECD 408 GLP | Mice | Oral Food | 0, 3125,6250, 12500, 25000 and 50000 ppm , ie ± 0, 554, 1246, 2860, 6780 and 16238 mg/kg bw/day 13 weeks | No effects on reproductive parameters at 6780 mg/kg bw/day or below | Males: ↓ in sperm density and ↑ in abnor...","effect":"Unlabeled table on page 67: - 8 - Ref 5, 7, 33 in submission dossier Sub-chronic toxicity study OECD 408 GLP | Mice | Oral Food | 0, 3125,6250, 12500, 25000 and 50000 ppm , ie ± 0, 554, 1246, 2860, 6780 and 16238 mg/kg bw/day 13 weeks | No effects on reproductive parameters at 6780 mg/kg bw/day or below | Males: ↓ in sperm density and ↑ in abnormal sperm morphology at 16238 mg/kg bw/day Females: ↑ in estrous cycles length at 16238 mg/kg bw/day | NOAEL = 1246 mg/kg bw /day based on systemic effects","page":67,"pdf":"sccs_o_247.pdf","row_type":"noael_study","study_id":"sccs_o_247_noael_052"}
SCCS_vision_codex	NOAEL	=311	mg/kg bw/day	rat	oral	14d	NOAEL study	{"citation":"Ref.: 30 14-day oral toxicity in mouse (1985-88) Benzophenone-3 was administered in the diet to five B6C3F1 mice per sex and group at concentrations of 0, 3,125","dose":"2,238 mg/kg bw/day: increased liver weights in males and females associated with the presence of cytoplasmic vacuolisation of hepatocytes; increased kidney weights in males 3,868 mg/kg bw/day: reduced feed consumption in males and females; reduced body weight gain in males; increased liver weights in males and females associated with the presenc...","effect":"2,238 mg/kg bw/day: increased liver weights in males and females associated with the presence of cytoplasmic vacuolisation of hepatocytes; increased kidney weights in males 3,868 mg/kg bw/day: reduced feed consumption in males and females; reduced body weight gain in males; increased liver weights in males and females associated with the presence of cytoplasmic vacuolisation of hepatocytes; increased kidney weights in males; focal dilatation of renal tubules in the cortex and/or medulla Study authors' conclusion: NOAEL (14d-oral) = 295/311 mg/kg bw/day for the male/female rat. Ref.: 30 14-day oral toxicity in mouse (1985-88) Benzophenone-3 was administered in the diet to five B6C3F1 mice per sex and group at concentrations of 0, 3,125; 6,250; 12,500; 25,000 and 50,000 ppm for 2 weeks. The dietary test substance preparations were analyzed for stability and proved to be stable in the diet for at least 3 weeks. Clinical examinations covering clinical signs, mortality, body weight and food consumption were performed in all animals","page":12,"pdf":"sccp_o_078.pdf","row_type":"noael_study","study_id":"sccp_o_078_noael_001"}
SCCS_vision_codex	NOAEL	=1050	mg/kg bw/day	rat	oral	14d	repeated dose toxicity	{"citation":"Ref.: 30 B","dose":"y: increased liver weights in males and females associated with the presence of cytoplasmic vacuolisation of hepatocytes 8,648 mg/kg bw/day: increased liver weights in males and females associated with the presence of cytoplasmic vacuolisation of hepatocytes; decreased kidney weight in males 20,796 mg/kg bw/day: reduced body weight gain; increas...","effect":"y: increased liver weights in males and females associated with the presence of cytoplasmic vacuolisation of hepatocytes 8,648 mg/kg bw/day: increased liver weights in males and females associated with the presence of cytoplasmic vacuolisation of hepatocytes; decreased kidney weight in males 20,796 mg/kg bw/day: reduced body weight gain; increased liver weights in males and females associated with the presence of cytoplasmic vacuolisation of hepatocytes; decreased kidney weight in males Study authors' conclusion: NOAEL (14d-oral) = 992/1050 mg/kg bw/day for the male/female mouse. Ref.: 30 B. Subacute dermal administration to rats and mice 14-day dermal toxicity in rat (1985-88) Five F344/N rats per sex and group received Benzophenone-3 at dose levels of 0, 1.25, 2.5, 5.0, 10.0, 20.0 mg/rat in acetone or lotion as vehicle for 5 days per week for 2 weeks. A constant volume of 0.25 ml/rat was applied over a fixed standard area (10%) of the interscapular region. The area was clipped 24 hours prior to initial application and weekl","page":13,"pdf":"sccp_o_078.pdf","row_type":"noael_study","study_id":"sccp_o_078_noael_002"}
SCCS_vision_codex	NOAEL	=140	mg/kg bw/day	rat	oral	14d	NOAEL study	{"citation":"Ref.: 30 28-day dermal toxicity in rat (1985-88) A publication of 1995 describes how 6 male Sprague-Dawley rats per group received Benzophenone-3, formulated in petroleum jelly base, at","dose":"7.0 mg/kg bw/day: no adverse effects noted 13.6 mg/kg bw/day: no adverse effects noted 27.7 mg/kg bw/day: slightly increased liver weights in females 54.9 mg/kg bw/day: slightly increased liver weights in female 110 mg/kg bw/day: slightly increased liver weights in females; slightly increased kidney weights Study authors' conclusion:","effect":"ficed and macroscopically examined, organs were weighed and comprehensive histopathology was performed. The following effects were noted (dietary levels were converted to dosages): 7.0 mg/kg bw/day: no adverse effects noted 13.6 mg/kg bw/day: no adverse effects noted 27.7 mg/kg bw/day: slightly increased liver weights in females 54.9 mg/kg bw/day: slightly increased liver weights in female 110 mg/kg bw/day: slightly increased liver weights in females; slightly increased kidney weights Study authors' conclusion: NOAEL (14d-dermal) = 100/140 mg/kg bw/day for the male/female rat. Ref.: 30 28-day dermal toxicity in rat (1985-88) A publication of 1995 describes how 6 male Sprague-Dawley rats per group received Benzophenone-3, formulated in petroleum jelly base, at dosage levels of 0 and 100 mg/kg bw/day, twice daily for 4 weeks. Clinical examinations covering clinical signs and body weight were performed in all animals. Blood samples for haematology and clinical chemistry were taken prior to the start of treatment and on day 16.","page":13,"pdf":"sccp_o_078.pdf","row_type":"noael_study","study_id":"sccp_o_078_noael_003"}
SCCS_vision_codex	NOAEL	=432	mg/kg bw/day	rat	oral	14d	repeated dose toxicity	{"citation":"Ref.: 30 3","dose":"24.8 mg/kg bw/day: none 48.4 mg/kg bw/day: none 100 mg/kg bw/day: none 196 mg/kg bw/day: increased liver weight 388 mg/kg bw/day: increased liver weight Study authors' conclusion:","effect":"tions covering clinical signs, mortality, body weight and food consumption were performed in all animals. At termination of treatment, all animals were sacrificed and macroscopically examined, organs were weighed and comprehensive histopathology was performed. The following effects were noted (applied doses were converted to dosages): 24.8 mg/kg bw/day: none 48.4 mg/kg bw/day: none 100 mg/kg bw/day: none 196 mg/kg bw/day: increased liver weight 388 mg/kg bw/day: increased liver weight Study authors' conclusion: NOAEL (14d-dermal) = 384/432 mg/kg bw/day for the male/female mouse. Ref.: 30 3.3.5.2 Sub-chronic (90 days) oral / dermal / inhalation toxicity - rat/mouse A. Sub-chronic oral administration to rats and mice 90-day oral toxicity in rat (1) (1972) Benzophenone-3 (source and batch not cited) was examined in 12 male and 12 female rats per sex and group at dosages of approximately 0, 20, 100, 500 and 1,000 mg/kg bw/day for 13 weeks. The animals were observed for clinical findings and body weight and food consumption was","page":14,"pdf":"sccp_o_078.pdf","row_type":"noael_study","study_id":"sccp_o_078_noael_004"}
SCCS_vision_codex	NOAEL	=100	mg/kg bw/day	rat	oral	12 weeks	NOAEL study	{"citation":"Ref.: 44 90-day oral toxicity in rat (2) (1985-1988) Ten F344/N rats per sex and group received Benzophenone-3 in concentrations of 0","dose":"NOEL (90d-oral) = 100 mg/kg bw/day for male and female rats.","effect":"males; anaemia, lymphocytosis and reduced number of granulocytes after 12 weeks in females; decreased absolute weights of the thymus, heart, pituitary gland, lungs, spleen, adrenal glands, and gonads in males and females; decreased relative weights of the pituitary gland, thymus, heart and adrenal glands in males and females; decreased relative weights of the lungs and spleen in females; increased relative thyroid weight in females; degenerative nephritis in kidneys of males and females Study authors' conclusion: NOEL (90d-oral) = 100 mg/kg bw/day for male and female rats. Ref.: 44 90-day oral toxicity in rat (2) (1985-1988) Ten F344/N rats per sex and group received Benzophenone-3 in concentrations of 0; 3,125; 6,250; 12,500; 25,000 and 50,000 ppm in the diet for 13 weeks. The dietary test substance preparations were analyzed for stability and proved to be stable in the diet for at least 3 weeks. Clinical examinations covering clinical signs, mortality, body weight and food consumption were performed in all animals at regula","page":15,"pdf":"sccp_o_078.pdf","row_type":"noael_study","study_id":"sccp_o_078_noael_005"}
SCCS_vision_codex	NOAEL	=393	mg/kg bw/day	rat	oral	90d	NOAEL study	{"citation":"Ref.: 30","dose":"NOAEL (90d-oral) = 429/393 mg/kg bw/day for the male/female rat.","effect":"SCCP/1069/06 OPINION ON BENZOPHENONE-3 16 Study authors' conclusion: NOAEL (90d-oral) = 429/393 mg/kg bw/day for the male/female rat. Ref.: 30","page":16,"pdf":"sccp_o_078.pdf","row_type":"noael_study","study_id":"sccp_o_078_noael_006"}
SCCS_vision_codex	NOAEL	=1425	mg/kg bw/day	rat	oral	90d	repeated dose toxicity	{"citation":"Ref.: 30 B","dose":"y: increased liver weight 2,860 mg/kg bw/day: increased liver weight 6,780 mg/kg bw/day: decreased body weight gain in males and females; increased liver weight; minimal cytoplasmic vacuolisation of hepatocytes 16,238 mg/kg bw/day: decreased body weight gain in males and females; minimal renal lesions in males; increased liver weight; minimal cy...","effect":"y: increased liver weight 2,860 mg/kg bw/day: increased liver weight 6,780 mg/kg bw/day: decreased body weight gain in males and females; increased liver weight; minimal cytoplasmic vacuolisation of hepatocytes 16,238 mg/kg bw/day: decreased body weight gain in males and females; minimal renal lesions in males; increased liver weight; minimal cytoplasmic vacuolisation of hepatocytes; decreased sperm density and increased abnormal sperm in males; increased estrous cycle length in females Study authors' conclusion: NOAEL (90d-oral) = 1068/1425 mg/kg bw/day for the male/female mouse. Ref.: 30 B. Sub-chronic dermal administration to rats and mice 90-day dermal toxicity in rat (1985-88) Ten F344/N rats per sex and groups received Benzophenone-3 preparations at dosage levels of 0, 12.5, 25, 50, 100, 200 mg/kg bw/day in acetone for 5 days per week over a period of 13 weeks. A constant volume of 0.25 ml/rat was applied over a fixed standard area (10%) of the interscapular region. The area was clipped 24 hours prior to initial applic","page":17,"pdf":"sccp_o_078.pdf","row_type":"noael_study","study_id":"sccp_o_078_noael_007"}
SCCS_vision_codex	NOAEL	=200	mg/kg bw/day	rat	dermal	90d	NOAEL study	{"citation":"Ref.: 30 90-day dermal toxicity in mouse Ten B6C3F1 mice per sex and group received Benzophenone-3 preparations at dosage levels of 0, 22","dose":"SCCP/1069/06 OPINION ON BENZOPHENONE-3 18 200 mg/kg bw/day: non-dosage related increase in relative kidney weight in females; decreased reticulocyte count; increased platelet count; increased whole blood cell count produced by lymphocytosis Study authors' conclusion:","effect":"SCCP/1069/06 OPINION ON BENZOPHENONE-3 18 200 mg/kg bw/day: non-dosage related increase in relative kidney weight in females; decreased reticulocyte count; increased platelet count; increased whole blood cell count produced by lymphocytosis Study authors' conclusion: NOAEL (90d-dermal) = 200 mg/kg bw/day for male and female rats. Ref.: 30 90-day dermal toxicity in mouse Ten B6C3F1 mice per sex and group received Benzophenone-3 preparations at dosage levels of 0, 22.8, 45.5, 91, 182, 364 mg/kg bw/day in acetone for 5 days per week over a period of 13 weeks. A constant volume of 0.1 ml was applied over a fixed standard area (10%) of the interscapular region. The area was clipped 24 hours prior to initial application and weekly thereafter. The preparations in acetone were analyzed fo","page":18,"pdf":"sccp_o_078.pdf","row_type":"noael_study","study_id":"sccp_o_078_noael_008"}
SCCS_vision_codex	NOAEL	=364	mg/kg bw/day	rat	oral	90d	repeated dose toxicity	{"citation":"Ref.: 30 3","dose":"Sperm morphology/motility and vaginal cytology examinations were performed at dosage levels of 0, 22.8, 91, 364 mg/kg bw/day.","effect":"ll animals at regular intervals. Sperm morphology/motility and vaginal cytology examinations were performed at dosage levels of 0, 22.8, 91, 364 mg/kg bw/day. At termination of treatment, all animals were sacrificed and macroscopically examined, organs were weighed and comprehensive histopathology was performed. At all dosage levels, a mild increase in relative kidney weight in males, together with a decrease in epididymal sperm density, was noted. No other abnormalities were observed. Study authors' conclusion: NOAEL (90d-dermal) = 364 mg/kg bw/day for male and female mice. Ref.: 30 3.3.5.3 Chronic (> 12 months) toxicity No data. 3.3.5.4 Overall conclusion of the submission authors on repeated dose toxicity The toxicity of Benzophenone-3 after repeated application was comprehensively examined in subacute up to subchronic studies in rats and mice using the oral and dermal application route. The systemic toxicity after repeated oral application was low and effects could mainly be observed at dose levels which were in the ran","page":18,"pdf":"sccp_o_078.pdf","row_type":"noael_study","study_id":"sccp_o_078_noael_009"}
SCCS_vision_codex	NOAEL	=6250	ppm	rat	oral	subchronic	repeated dose toxicity	{"dose":"ly >3000 mg/kg bw/day in rats and >13000 mg/kg bw/day in mice after subchronic oral treatment, an impairment of selective reproductive parameters was noted.","effect":"ly >3000 mg/kg bw/day in rats and >13000 mg/kg bw/day in mice after subchronic oral treatment, an impairment of selective reproductive parameters was noted. However, these are finally assessed in the reproduction section within this dossier (section 3.3.8 Reproductive toxicity). Repeated dermal application of up to 13 weeks in rats and mice did not lead to any reliable substance-related local or systemic findings up to the highest dose level investigated in each case. Finally, the reliable No-Adverse-Effect-Level (NOAEL) for subchronic toxicity after oral treatment was 6250 ppm (429/393 mg/kg bw/day in males/females) in rats and 6250 ppm (1068/1425 mg/kg bw/day in males/females) in mice.","page":18,"pdf":"sccp_o_078.pdf","row_type":"noael_study","study_id":"sccp_o_078_noael_010"}
SCCS_vision_codex	NOAEL	=828	mg/kg bw/day	rat	oral	-	reproductive toxicity	{"citation":"Ref.: 24, 30","dose":"204 mg/kg bw/day: no deviations among the reproductive parameters studied 828 mg/kg bw/day: no deviations among the reproductive parameters studied 3,458 mg/kg bw/day: males: decreased right caudal, testicular and epididymal weights; decreased sperm number per caudal tissue females : prolonged cycle length.","effect":"ssue weight. Observations in the females included vaginal cytology examinations and estrual cyclicity. The following effects were noted (dietary levels were converted to dosages): 204 mg/kg bw/day: no deviations among the reproductive parameters studied 828 mg/kg bw/day: no deviations among the reproductive parameters studied 3,458 mg/kg bw/day: males: decreased right caudal, testicular and epididymal weights; decreased sperm number per caudal tissue females : prolonged cycle length. Study authors' conclusion: NOAEL (reproduction) = 828 mg/kg bw/day for male and female rats. Ref.: 24, 30","page":21,"pdf":"sccp_o_078.pdf","row_type":"noael_study","study_id":"sccp_o_078_noael_012"}
SCCS_vision_codex	NOAEL	=2860	mg/kg bw/day	mouse	oral	-	reproductive toxicity	{"citation":"Ref.: 24, 30 Reproductive Assessment by Continuous Breeding (RACB) in the mouse (1991) The \"Continuous Breeding Protocol\" is a test design used by the US National Toxicology Program","dose":"554 mg/kg bw/day: no deviations among the reproductive parameters studied 2,860 mg/kg bw/day: no deviations among the reproductive parameters studied 16,238 mg/kg bw/day: decreased sperm number per caudal tissue and increased incidence of abnormal sperm in the males Study authors' conclusion:","effect":"d morphology and sperm number per caudal tissue weight. Observations in the females included vaginal cytology examinations and estrual cyclicity. The following effects were noted (dietary levels were converted to dosages): 554 mg/kg bw/day: no deviations among the reproductive parameters studied 2,860 mg/kg bw/day: no deviations among the reproductive parameters studied 16,238 mg/kg bw/day: decreased sperm number per caudal tissue and increased incidence of abnormal sperm in the males Study authors' conclusion: NOAEL (reproduction) = 2,860 mg/kg bw/day for male and female mice. Ref.: 24, 30 Reproductive Assessment by Continuous Breeding (RACB) in the mouse (1991) The \"Continuous Breeding Protocol\" is a test design used by the US National Toxicology Program. It consists of four related tasks (see figure below), which are not all necessarily performed for every compound tested. TASK 4 Offspring assessment F1 generation (Control + 1 dosed group) TASK 3 Determination of affected sex (F0 generation) TASK 4 Offspring assessment F","page":22,"pdf":"sccp_o_078.pdf","row_type":"noael_study","study_id":"sccp_o_078_noael_013"}
SCCS_vision_codex	NOAEL	=9500	mg/kg bw/day	mouse	dermal	20-day	reproductive toxicity	{"citation":"Ref.: 9, 31 B","dose":"5 dams died unexpectedly during the Task 2 20-day period 3,950 mg/kg bw/day: reduced number of pups / litter; reduced dam weights;","effect":"ation, necropsy was performed, organs were weighed and preserved for histopathology (especially reproductive organs). The following effects were noted: 1,850 mg/kg bw/day: 5 dams died unexpectedly during the Task 2 20-day period 3,950 mg/kg bw/day: reduced number of pups / litter; reduced dam weights; 4 dams died unexpectedly during the Task 2 20-day period 9,050mg/kg bw/day: reduced number of pups / litter; reduced dam weights; 9 dams died unexpectedly during the Task 2 20-day period Study authors' conclusion: NOAEL (fertility) = 8600/9500 mg/kg bw/day for male/female mice. Ref.: 9, 31 B. Dermal reproduction toxicity screening tests A short communication published in 1993 describes the assessment of the reproductive toxic potential of Benzophenone-3 in male B6C3F1 mice after a 13-week repeated dermal application of dosages of 0, 20, 100 and 400 mg/kg bw/day. Reproductive organ weights, cauda epididymal sperm concentration, proportion of motile and abnormal sperm and testicular spermatid concentration were determined and tes","page":23,"pdf":"sccp_o_078.pdf","row_type":"noael_study","study_id":"sccp_o_078_noael_014"}
SCCS_vision_codex	NOAEL	=400	mg/kg bw/day	mouse	oral	sub-chronic	repeated dose toxicity	{"citation":"Ref.: 21 Finally, the results of the examinations of sperm morphology/motility and vaginal cytology in the dermal sub-chronic toxicity studies as described under 3","dose":"Since neither any effect on body weight gain nor any abnormalities in the measured reproductive parameters were noted, the study authors conclude that topically applied Benzophenone-3 has no reproductive toxic potential in male B6C3F1 mice at dosages up to 400 mg/kg bw/day.","effect":"0 mg/kg bw/day. Reproductive organ weights, cauda epididymal sperm concentration, proportion of motile and abnormal sperm and testicular spermatid concentration were determined and testicular histology was evaluated. Since neither any effect on body weight gain nor any abnormalities in the measured reproductive parameters were noted, the study authors conclude that topically applied Benzophenone-3 has no reproductive toxic potential in male B6C3F1 mice at dosages up to 400 mg/kg bw/day. Study authors' conclusion: NOAEL (reproduction) = 400 mg/kg bw/day for male and female mice. Ref.: 21 Finally, the results of the examinations of sperm morphology/motility and vaginal cytology in the dermal sub-chronic toxicity studies as described under 3.3.5.2.B, revealed a decrease in epididymal sperm density in the male mice. However, this finding is considered incidental 3 Stability of Benzophenone-3 in the diet : at least 3 weeks","page":23,"pdf":"sccp_o_078.pdf","row_type":"noael_study","study_id":"sccp_o_078_noael_015"}
SCCS_vision_codex	NOAEL	=1900	mg/kg bw/day	rat	oral	developmental	reproductive toxicity	{"dose":"The NOAEL for fertility was the highest investigated dosage level of 8600/9500 mg/kg bw/day in male/female mice.","effect":"a RACB (Reproductive Assessment by Continuous Breeding) study in mice. The NOAEL for fertility was the highest investigated dosage level of 8600/9500 mg/kg bw/day in male/female mice. Within this study the reproductive performance was affected in the form of a slightly lower number of live pups at birth. Signs of developmental toxicity consisted of impaired body weight/body weight gain of the pups. However, in any case these effects were only noted at a dosage level with overt parental toxicity. Consequently, the NOAEL for systemic, reproductive and developmental toxicity was 1800/1900 mg/kg bw/day in males/females. Repeated oral application of Benzophenone-3 for 13 weeks to rats and mice caused only slight effects in selective parameters accompanied with overt systemic toxicity at the highest investigated dosage levels of 3656/3261 mg/kg bw/day in male/female rats and 13937/18539 mg/kg bw/day in male/female mice). In rats, the epididymal sperm count was reduced and a decreased absolute cauda, epididymal and testis weight as a","page":25,"pdf":"sccp_o_078.pdf","row_type":"noael_study","study_id":"sccp_o_078_noael_019"}
SCCS_vision_codex	NOAEL	=200	mg/kg bw/d	rat	oral	subchronic	repeated dose toxicity	{"dose":"In any case, the next lower investigated dose level was a clear NOAEL for the investigated reproductive parameters.","effect":"ecreased absolute cauda, epididymal and testis weight as a consequence of the reduced body weight was noted. In female rats, an increase in the length of the oestrous cycle was noted. In mice, a decrease in the epididymal sperm count and an increase the incidence of abnormal sperm was recorded, while female mice (as in rats) revealed an increase in the length of the oestrous cycle. However, in rats and in mice, the oestrous cyclicity was not affected. In any case, the next lower investigated dose level was a clear NOAEL for the investigated reproductive parameters. After subchronic dermal application for 13 weeks no clear or reliable effect on selective reproduction parameter was noted and therefore, the NOAEL was in each case the highest dose level applied, namely 200 mg/kg bw/d in rats and 364 mg/kg bw/d in mice. Although in mice a decrease in the epididymal sperm count was reported at all investigated dose levels, a relation to treatment is considered as very unlikely since in the oral study the administration of dose levels","page":25,"pdf":"sccp_o_078.pdf","row_type":"noael_study","study_id":"sccp_o_078_noael_020"}
SCCS_vision_codex	NOAEL	=411	mg/kg bw/day	rat	oral	90d	repeated dose toxicity	{"dose":"Therefore, according to the submission, the oral NOAEL corresponds to 411 mg/kg bw/day.","effect":"SCCS-rejected applicant NOAEL: ether with some effects on the identified target organs being the kidney and the liver. These effects were partly associated with changes in clinical chemistry. Very often the most susceptible parameter was the increase in liver weight. The latter, however, without any histopathological correlate, is not considered by the submission authors to reflect an adverse effect per se but should be considered as an adaptive metabolic response which is known to be reversible. Therefore, according to the submission, the oral NOAEL corresponds to 411 mg/kg bw/day. With regard to the results of the dermal repeated dose studies, a dermal NOAEL of 200 mg/kg bw/day is put forward, on the assumption that deviations without dose-response relationship and without correlated histopathological findings (e.g. the decreased reticulocyte count, increased relative kidney weight, increased platelet count and whole blood cell count in the 90d dermal study in rat) should not be taken into account.","page":35,"pdf":"sccp_o_078.pdf","row_type":"noael_study","study_id":"sccp_o_078_noael_023"}
SCCS_vision_codex	NOAEL	=18	-	-	oral	subchronic	repeated dose toxicity	{"effect":"Unlabeled table on page 18: Finally, the reliable No-Adverse-Effect-Level (NOAEL) for subchronic toxicity after oral","page":18,"pdf":"sccp_o_078.pdf","row_type":"noael_study","study_id":"sccp_o_078_noael_036"}
SCCS_vision_codex	NOAEL	=1980	-	-	-	-	NOAEL study	{"effect":"Unlabeled table on page 19: A number of publications (1980-1992) describe the results of Benzophenone-3 studied in","page":19,"pdf":"sccp_o_078.pdf","row_type":"noael_study","study_id":"sccp_o_078_noael_038"}
SCCS_vision_codex	NOAEL	=36	-	-	-	-	NOAEL study	{"effect":"Unlabeled table on page 19: and a title page [36] to a more extensive description of the materials and methods [73].","page":19,"pdf":"sccp_o_078.pdf","row_type":"noael_study","study_id":"sccp_o_078_noael_039"}
SCCS_vision_codex	NOAEL	=9	-	-	-	-	NOAEL study	{"effect":"Unlabeled table on page 19: bacteria both, with and without metabolic activation (S9 mix from the liver of Aroclor 1254-","page":19,"pdf":"sccp_o_078.pdf","row_type":"noael_study","study_id":"sccp_o_078_noael_040"}
SCCS_vision_codex	NOAEL	=10	%	-	-	-	NOAEL study	{"effect":"Unlabeled table on page 19: prepared immediately prior to use and contained 10% S9. The tested Salmonella","page":19,"pdf":"sccp_o_078.pdf","row_type":"noael_study","study_id":"sccp_o_078_noael_041"}
SCCS_vision_codex	NOAEL	=97	-	-	-	-	NOAEL study	{"effect":"Unlabeled table on page 19: typhimurium strains were combinations of TA97, TA98, TA100, TA1535, TA1537 and/or","page":19,"pdf":"sccp_o_078.pdf","row_type":"noael_study","study_id":"sccp_o_078_noael_042"}
SCCS_vision_codex	NOAEL	=1538	-	-	-	-	NOAEL study	{"effect":"Unlabeled table on page 19: TA1538 and were exposed to the test substance at various concentrations of","page":19,"pdf":"sccp_o_078.pdf","row_type":"noael_study","study_id":"sccp_o_078_noael_043"}
SCCS_vision_codex	NOAEL	=-3	-	-	-	-	NOAEL study	{"effect":"Unlabeled table on page 19: Benzophenone-3 with and without S9 mix. Positive controls were included to demonstrate","page":19,"pdf":"sccp_o_078.pdf","row_type":"noael_study","study_id":"sccp_o_078_noael_044"}
SCCS_vision_codex	NOAEL	=73	-	-	-	-	NOAEL study	{"effect":"Unlabeled table on page 19: Bacteriotoxicity was reported [73] to be observed at a varying degree at and above 333","page":19,"pdf":"sccp_o_078.pdf","row_type":"noael_study","study_id":"sccp_o_078_noael_045"}
SCCS_vision_codex	NOAEL	=1000	-	-	-	-	NOAEL study	{"effect":"Unlabeled table on page 19: µg/plate and at 1000 µg/plate in all tested strains (TA98, TA100, TA1535, TA1537). In that","page":19,"pdf":"sccp_o_078.pdf","row_type":"noael_study","study_id":"sccp_o_078_noael_046"}
SCCS_vision_codex	NOAEL	=30	%	-	-	-	NOAEL study	{"effect":"Unlabeled table on page 19: weak mutagenic response using 30% of S9 hamster mix.","page":19,"pdf":"sccp_o_078.pdf","row_type":"noael_study","study_id":"sccp_o_078_noael_048"}
SCCS_vision_codex	NOAEL	=2	-	-	-	-	NOAEL study	{"effect":"Unlabeled table on page 19: the respective controls, the increase in the numbers of revertants was less than 2-fold","page":19,"pdf":"sccp_o_078.pdf","row_type":"noael_study","study_id":"sccp_o_078_noael_050"}
SCCS_vision_codex	NOAEL	=3	-	-	-	-	NOAEL study	{"effect":"Unlabeled table on page 19: the tested concentration range between 3 and 333 µg/plate. All other studies (not including","page":19,"pdf":"sccp_o_078.pdf","row_type":"noael_study","study_id":"sccp_o_078_noael_052"}
SCCS_vision_codex	NOAEL	=8	-	-	-	-	NOAEL study	{"citation":"Ref.: 8, 30, 36, 73","effect":"Unlabeled table on page 19: Ref.: 8, 30, 36, 73","page":19,"pdf":"sccp_o_078.pdf","row_type":"noael_study","study_id":"sccp_o_078_noael_057"}
SCCS_vision_codex	NOAEL	=1992	-	-	-	-	NOAEL study	{"effect":"Unlabeled table on page 19: A US National Toxicology program report (1992) briefly describes the results of cytogenetic","page":19,"pdf":"sccp_o_078.pdf","row_type":"noael_study","study_id":"sccp_o_078_noael_058"}
SCCS_vision_codex	NOAEL	=5	-	-	-	-	NOAEL study	{"dose":"Unlabeled table on page 19: exchanges (effective dose range 5-50µg/ml) and chromosomal aberrations (20-45µg/ml) in","effect":"Unlabeled table on page 19: exchanges (effective dose range 5-50µg/ml) and chromosomal aberrations (20-45µg/ml) in","page":19,"pdf":"sccp_o_078.pdf","row_type":"noael_study","study_id":"sccp_o_078_noael_060"}
SCCS_vision_codex	NOAEL	=1254	-	rat	-	-	NOAEL study	{"effect":"Unlabeled table on page 19: the presence of Aroclor 1254-induced male Sprague Dawley rat liver S9.","page":19,"pdf":"sccp_o_078.pdf","row_type":"noael_study","study_id":"sccp_o_078_noael_061"}
SCCS_vision_codex	NOAEL	=24	-	-	-	prenatal	developmental toxicity	{"effect":"Unlabeled table on page 24: effect and that the NOAEL for maternal and prenatal developmental toxicity is","page":24,"pdf":"sccp_o_078.pdf","row_type":"noael_study","study_id":"sccp_o_078_noael_066"}
SCCS_vision_codex	NOAEL	=1	-	-	-	-	NOAEL study	{"effect":"Unlabeled table on page 24: Date of study: 01-16 November 2004","page":24,"pdf":"sccp_o_078.pdf","row_type":"noael_study","study_id":"sccp_o_078_noael_069"}
SCCS_vision_codex	NOAEL	=67	-	-	-	-	NOAEL study	{"effect":"Unlabeled table on page 24: Guideline/method: Annex V to Dir. 67/548/EEC, Method B.31; OECD Guideline 414","page":24,"pdf":"sccp_o_078.pdf","row_type":"noael_study","study_id":"sccp_o_078_noael_070"}
SCCS_vision_codex	NOAEL	=25	-	-	-	-	NOAEL study	{"effect":"Unlabeled table on page 24: Group size: 25 mated females per dosage group","page":24,"pdf":"sccp_o_078.pdf","row_type":"noael_study","study_id":"sccp_o_078_noael_071"}
SCCS_vision_codex	NOAEL	=99.8	%	-	-	-	NOAEL study	{"effect":"Unlabeled table on page 24: Purity: 99.8% (GC-FID)","page":24,"pdf":"sccp_o_078.pdf","row_type":"noael_study","study_id":"sccp_o_078_noael_073"}
SCCS_vision_codex	NOAEL	=35	-	-	oral	-	NOAEL study	{"effect":"Unlabeled table on page 35: reversible. Therefore, according to the submission, the oral NOAEL corresponds to","page":35,"pdf":"sccp_o_078.pdf","row_type":"noael_study","study_id":"sccp_o_078_noael_080"}
SCCS_vision_codex	NOAEL	=411	mg/kg bw/day	rat	oral	90d	repeated dose toxicity	{"dose":"Therefore, according to the 2005-submission, the oral NOAEL corresponded to 411 mg/kg bw/day.","effect":"SCCS-rejected applicant NOAEL: ether with effects on the identified target organs being the kidney and the liver. These effects were partly associated with changes in clinical chemistry. Very often the most susceptible parameter was the increase in liver weight. The latter, however, without any histopathological correlate, is not considered by the submission authors to reflect an adverse effect per se but should be considered as an adaptive metabolic response which is known to be reversible. Therefore, according to the 2005-submission, the oral NOAEL corresponded to 411 mg/kg bw/day. With regard to the results of the dermal repeated dose studies, a dermal NOAEL of 200 mg/kg bw/day was put forward, on the assumption that deviations without dose-response relationship and without correlated histopathological findings (e.g. the decreased reticulocyte count, increased relative kidney weight, increased platelet count and whole blood cell count in the 90d dermal study in rat) should not be taken into account. 8 A teratogenicity study in rat showed BP-3 to be non-ter","page":6,"pdf":"sccp_o_159.pdf","row_type":"noael_study","study_id":"sccp_o_159_noael_001"}
SCCS_vision_codex	NOAEL	=200	mg/kg bw/day	rat	oral	90d	repeated dose toxicity	{"dose":"Therefore, according to the 2005-submission, the oral NOAEL corresponded to 411 mg/kg bw/day.","effect":"SCCS-rejected applicant NOAEL: ciated with changes in clinical chemistry. Very often the most susceptible parameter was the increase in liver weight. The latter, however, without any histopathological correlate, is not considered by the submission authors to reflect an adverse effect per se but should be considered as an adaptive metabolic response which is known to be reversible. Therefore, according to the 2005-submission, the oral NOAEL corresponded to 411 mg/kg bw/day. With regard to the results of the dermal repeated dose studies, a dermal NOAEL of 200 mg/kg bw/day was put forward, on the assumption that deviations without dose-response relationship and without correlated histopathological findings (e.g. the decreased reticulocyte count, increased relative kidney weight, increased platelet count and whole blood cell count in the 90d dermal study in rat) should not be taken into account. 8 A teratogenicity study in rat showed BP-3 to be non-teratogenic under the conditions of the test. Only at the highest dosage level, which also caused maternal toxicity,","page":6,"pdf":"sccp_o_159.pdf","row_type":"noael_study","study_id":"sccp_o_159_noael_002"}
SCCS_vision_codex	NOAEL	=1.78	mg/kg bw/day	rat	dermal	-	dermal absorption	{"dose":"9.9% [mean (3.1%) + 2 SD (2*3.4%)] Applied dose (sunscreen):","effect":"SCCP/1201/08 Opinion on benzophenone-3 13 3.2.4 Safety evaluation (including calculation of the MoS) BP-3 as a UV-filter in sunscreens up to 6% Dermal absorption (6% formulation): 9.9% [mean (3.1%) + 2 SD (2*3.4%)] Applied dose (sunscreen): 18 g/day Typical human body weight: 60 kg No observed effect level NOAEL (terato-rat): 200 mg/kg bw/day Systemic exposure dose (SED) = (18.103 mg/day * 6/100 * 9.9/100) / 60 kg = 1.78 mg/kg bw/day MoS = NOAEL / SED = 112 BP-3 as a UV-filter at 0.5% to protect cosmetic formulations against sunlight Dermal absorption (2% formulation): 8.0% [mean (4.0%) + 2 SD (2*2.0%)] Applied dose (all cosmetic products): 17.79 g/day Typical human body weight: 60 kg No observed effect level NOAEL (terato-rat): 200 mg/kg bw/day Systemic exposure dose (SED) = (17.79.103 mg/day * 0.5/100 * 8.0/100) / 60 kg = 0.119 mg/kg bw/day MoS = NOAEL / SED = 1686 3.2.5 Discussion A detailed discussion on the general toxicological profile of B","page":13,"pdf":"sccp_o_159.pdf","row_type":"noael_study","study_id":"sccp_o_159_noael_005"}
SCCS_vision_codex	NOAEL	=0.119	mg/kg bw/day	rat	dermal	-	dermal absorption	{"dose":"temic exposure dose (SED) = (18.103 mg/day * 6/100 * 9.9/100) / 60 kg = 1.78 mg/kg bw/day MoS = NOAEL / SED = 112 BP-3 as a UV-filter at 0.5% to protect cosmetic formulations against sunlight Dermal absorption (2% formulation):","effect":"temic exposure dose (SED) = (18.103 mg/day * 6/100 * 9.9/100) / 60 kg = 1.78 mg/kg bw/day MoS = NOAEL / SED = 112 BP-3 as a UV-filter at 0.5% to protect cosmetic formulations against sunlight Dermal absorption (2% formulation): 8.0% [mean (4.0%) + 2 SD (2*2.0%)] Applied dose (all cosmetic products): 17.79 g/day Typical human body weight: 60 kg No observed effect level NOAEL (terato-rat): 200 mg/kg bw/day Systemic exposure dose (SED) = (17.79.103 mg/day * 0.5/100 * 8.0/100) / 60 kg = 0.119 mg/kg bw/day MoS = NOAEL / SED = 1686 3.2.5 Discussion A detailed discussion on the general toxicological profile of BP-3 was given in SCCP/1069/06 and taken over under section 3.1 of the current opinion. The major shortcoming in the dossier was the absence of a sound dermal absorption study, allowing the calculation of the Margin of Safety for the UV-filter. The newly provided in vitro dermal absorption study is considered scientifically acceptable and shows a mean dermal absorption level of 19.3 µg/cm² or 3.1% of the applied dose fo","page":13,"pdf":"sccp_o_159.pdf","row_type":"noael_study","study_id":"sccp_o_159_noael_007"}
SCCS_vision_codex	NOAEL	=6	-	-	oral	-	NOAEL study	{"effect":"Unlabeled table on page 6: reversible. Therefore, according to the 2005-submission, the oral NOAEL corresponded to","page":6,"pdf":"sccp_o_159.pdf","row_type":"noael_study","study_id":"sccp_o_159_noael_009"}
SCCS_vision_codex	NOAEL	=7	-	-	-	developmental	developmental toxicity	{"effect":"Unlabeled table on page 7: skeletal aberrations were noted. The NOAEL-value for maternal and developmental","page":7,"pdf":"sccp_o_159.pdf","row_type":"noael_study","study_id":"sccp_o_159_noael_011"}
SCCS_vision_codex	NOAEL	=56	-	-	-	-	NOAEL study	{"effect":"Unlabeled table on page 7: (cid:56) Toxicokinetic studies indicated that BP-3 was readily biotransformed into its three major","page":7,"pdf":"sccp_o_159.pdf","row_type":"noael_study","study_id":"sccp_o_159_noael_013"}
SCCS_vision_codex	NOAEL	=-3	-	-	-	-	NOAEL study	{"effect":"Unlabeled table on page 7: The SCCP was unable to calculate the Margin of Safety for BP-3 as no scientifically","page":7,"pdf":"sccp_o_159.pdf","row_type":"noael_study","study_id":"sccp_o_159_noael_015"}
SCCS_vision_codex	NOAEL	=3.2	-	-	-	-	NOAEL study	{"effect":"Unlabeled table on page 7: 3.2 DATA INTRODUCED","page":7,"pdf":"sccp_o_159.pdf","row_type":"noael_study","study_id":"sccp_o_159_noael_016"}
SCCS_vision_codex	NOAEL	=13	-	rat	-	-	NOAEL study	{"effect":"Unlabeled table on page 13: The available teratogenicity study in the rat generated a NOAEL-value for maternal and","page":13,"pdf":"sccp_o_159.pdf","row_type":"noael_study","study_id":"sccp_o_159_noael_017"}
SCCS_vision_codex	NOAEL	=19.3	µg/cm	-	dermal	-	dermal absorption	{"dose":"Unlabeled table on page 13: and shows a mean dermal absorption level of 19.3 µg/cm² or 3.1% of the applied dose for a","effect":"Unlabeled table on page 13: and shows a mean dermal absorption level of 19.3 µg/cm² or 3.1% of the applied dose for a","page":13,"pdf":"sccp_o_159.pdf","row_type":"noael_study","study_id":"sccp_o_159_noael_018"}
SCCS_vision_codex	NOAEL	=6	%	-	-	-	NOAEL study	{"effect":"Unlabeled table on page 13: sunscreen (o/w or w/o) containing the maximum requested BP-3 concentration of 6%.","page":13,"pdf":"sccp_o_159.pdf","row_type":"noael_study","study_id":"sccp_o_159_noael_019"}
SCCS_vision_codex	NOAEL	=0.5	%	-	-	-	NOAEL study	{"effect":"Unlabeled table on page 13: protect formulations up to 0.5% in all types of cosmetics), the MoS of BP-3 is above 100.","page":13,"pdf":"sccp_o_159.pdf","row_type":"noael_study","study_id":"sccp_o_159_noael_023"}
SCCS_vision_codex	NOAEL	=411	mg/kg bw/day	rat	oral	90d	repeated dose toxicity	{"dose":"Therefore, according to the 2005- submission, the oral NOAEL corresponded to 411 mg/kg bw/day.","effect":"SCCS-rejected applicant NOAEL: ther with effects on the identified target organs being the kidney and the liver. These effects were partly associated with changes in clinical chemistry. Very often the most susceptible parameter was the increase in liver weight. The latter, however, without any histopathological correlate, is not considered by the submission authors to reflect an adverse effect per se but should be considered as an adaptive metabolic response which is known to be reversible. Therefore, according to the 2005- submission, the oral NOAEL corresponded to 411 mg/kg bw/day. With regard to the results of the dermal repeated dose studies, a dermal NOAEL of 200 mg/kg bw/day was put forward, on the assumption that deviations without dose-response relationship and without correlated histopathological findings (e.g. the decreased reticulocyte count, increased relative kidney weight, increased platelet count and whole blood cell count in the 90d dermal study in rat) should not be taken into account.’ The studies already included in the previous SCCS Opinion","page":25,"pdf":"sccs_o_247.pdf","row_type":"noael_study","study_id":"sccs_o_247_noael_001"}
SCCS_vision_codex	NOAEL	=200	mg/kg bw/day	rat	oral	90d	repeated dose toxicity	{"dose":"Therefore, according to the 2005- submission, the oral NOAEL corresponded to 411 mg/kg bw/day.","effect":"SCCS-rejected applicant NOAEL: iated with changes in clinical chemistry. Very often the most susceptible parameter was the increase in liver weight. The latter, however, without any histopathological correlate, is not considered by the submission authors to reflect an adverse effect per se but should be considered as an adaptive metabolic response which is known to be reversible. Therefore, according to the 2005- submission, the oral NOAEL corresponded to 411 mg/kg bw/day. With regard to the results of the dermal repeated dose studies, a dermal NOAEL of 200 mg/kg bw/day was put forward, on the assumption that deviations without dose-response relationship and without correlated histopathological findings (e.g. the decreased reticulocyte count, increased relative kidney weight, increased platelet count and whole blood cell count in the 90d dermal study in rat) should not be taken into account.’ The studies already included in the previous SCCS Opinion are not detailed in this Opinion; if they provide information on ED effects, they will be described in the secti","page":25,"pdf":"sccs_o_247.pdf","row_type":"noael_study","study_id":"sccs_o_247_noael_002"}
SCCS_vision_codex	NOAEL	=3000	ppm	-	-	developmental	developmental toxicity	{"dose":"However, on PND 4, pup body weights (male, female, and both) in the 10000 ppm exposure groups were statistically significantly decreased (both sexes approximately 5% lower) compared to the control group.","effect":"ere not statistically significantly different across the exposure groups on PND 1. However, on PND 4, pup body weights (male, female, and both) in the 10000 ppm exposure groups were statistically significantly decreased (both sexes approximately 5% lower) compared to the control group. This response was generally observed over subsequent pre-weaning weights, and by PND 21 combined live pup weight at this dose was 8% lower than control. Conclusion from the applicant Under the conditions of this study, the maternal NOAEL is 3000 ppm (206-478 mg/kg bw/day), based on reduced body weight gain during GD 6–9 and lactation day 4–21. The developmental NOEL is considered as 3000 ppm (206-478 mg/kg bw/day) based on impaired postnatal bodyweight performance at 10000 ppm (660-1609 mg/kg bw/day). (National Toxicology Program, 2020) Guidelines/Guidances: NTP Modified One-Generation study design GLP: FDA GLP","page":27,"pdf":"sccs_o_247.pdf","row_type":"noael_study","study_id":"sccs_o_247_noael_005"}
SCCS_vision_codex	NOAEL	=1000	ppm	-	-	-	NOAEL study	{"dose":"Therefore, a decrease in testosterone, which is significant at 3000 ppm (see Fig 7) supports the plausibility of a decrease in spermatocytes numbers.","effect":"reased in the tubules (see Fig 6); it is known that germinal cells are more sensitive than Sertoli cells to apoptosis (and Sertoli cells are less in numbers in the tubules). Moreover, it is well known that testosterone is needed for meiosis (De Gendt et al., 2004). Therefore, a decrease in testosterone, which is significant at 3000 ppm (see Fig 7) supports the plausibility of a decrease in spermatocytes numbers. Due to the effects on the ↓ of spermatocytes, the SCCS considered 3000 ppm as a LOAEL and therefore the NOAEL is 1000 ppm (67.9 mg /kg bw/day). This value will be used by the SCCS as a point of departure (POD) for the MoS calculation (see section 3.5 safety evaluation)","page":39,"pdf":"sccs_o_247.pdf","row_type":"noael_study","study_id":"sccs_o_247_noael_007"}
SCCS_vision_codex	NOAEL	>99	%	mouse	-	5 weeks	NOAEL study	{"dose":"The lowest dose (30 µg/kg/d) was chosen on the basis of equivalence to the EFSA Tolerable Daily Intake (TDI), whereas 212 µg/kg/d for being close to the 95 percentile reported in human biomonitoring studies in pregnant women, and 3000 µg/kg/d for equivalence to the NOAEL used by EFSA as a point of departure (POD) to derive the TDI.","effect":"housed in polysulfone cages with food (which may have contained phytoestrogens) were exposed orally to BP-3 (>99% purity) from Gestational Day (GD) until the day before weaning (Lactational Day 21 or LD21) at 3 doses of BP-3 (30, 212 and 3000 µg/kg/d). The lowest dose (30 µg/kg/d) was chosen on the basis of equivalence to the EFSA Tolerable Daily Intake (TDI), whereas 212 µg/kg/d for being close to the 95 percentile reported in human biomonitoring studies in pregnant women, and 3000 µg/kg/d for equivalence to the NOAEL used by EFSA as a point of departure (POD) to derive the TDI. The authors noted that doses around 10 times higher are needed in rodents to produce equivalent levels in human urine, which means that the highest dose was still environmentally relevant. The study included 2 negative control groups: 1 vehicle group and a second group of nulliparous female mice, which were housed under the same conditions. At 5 weeks post-weaning (once mammary gland involution was complete), mice were killed and mammary glands (the lef","page":40,"pdf":"sccs_o_247.pdf","row_type":"noael_study","study_id":"sccs_o_247_noael_008"}
SCCS_vision_codex	NOAEL	=67.9	mg/kg bw/d	-	oral	-	NOAEL study	{"dose":"The NOAEL of 67.9 mg/kg bw/d has been derived from Nakamura et al.","effect":"al Opinion Opinion on Benzophenone-3 (CAS No 131-57-7, EC No 205-031-5) _________________________________________________________________________________________________________________ 47 whilst there are indications from some studies to suggest that BP-3 may have endocrine effects, it is not conclusive enough at present to enable deriving a new endocrine-related toxicological point of departure for use in safety assessment. 3.5 SAFETY EVALUATION (INCLUDING CALCULATION OF THE MOS) The SCCS has used the lowest NOAEL values among those obtained from different toxicological endpoints for the calculation of MoS (summarised in Annex-1). The NOAEL of 67.9 mg/kg bw/d has been derived from Nakamura et al. (2015) study. Because of the evidence for rapid and almost complete absorption of BP-3 from the oral route, the SCCS has not applied any adjustment for bioavailability to this NOAEL value. Details of the calculation of systemic exposure dose (SED) are presented in the Tables in Annex-2. The calculation of MoS for different product","page":47,"pdf":"sccs_o_247.pdf","row_type":"noael_study","study_id":"sccs_o_247_noael_009"}
SCCS_vision_codex	NOAEL	=6	%	rat	oral	prenatal	developmental toxicity	{"dose":"Details of the calculation of systemic exposure dose (SED) are presented in the Tables in Annex-2.","effect":"et al. (2015) study. Because of the evidence for rapid and almost complete absorption of BP-3 from the oral route, the SCCS has not applied any adjustment for bioavailability to this NOAEL value. Details of the calculation of systemic exposure dose (SED) are presented in the Tables in Annex-2. The calculation of MoS for different product types are given in Table 3 below: Table 3: Calculation of Margin of Safety for different products containing BP-3 Products Conc. Surface Systemic Exposure Dose (SED) mg/kg bw/d NOAEL* MOS Dermal Inhalation Oral Total UV cream 6% whole body 1.782 0 0 1.782 67.9 38 UV aerosolised spray 6% whole body 1.782 0.105 0 1.887 67.9 36 UV pump spray 6% whole body 1.782 0.001053 0 1.783 67.9 38 UV face cream 6% face 0.152 0 0 0.152 67.9 447 UV hand cream 6% hand 0.214 0 0 0.214 67.9 317 Non-UV** 0.50% whole body 0.116 0 0 0.116 67.9 585 Lipstick 6% lips 0.000 0 0.054 0.054 67.9 1257 * derived from prenatal and postnatal developmental study, oral, rat (Nakamura et al., 2015) ** to protect cosmetic formulat","page":47,"pdf":"sccs_o_247.pdf","row_type":"noael_study","study_id":"sccs_o_247_noael_012"}
SCCS_vision_codex	NOAEL	=1625	-	rat	-	-	NOAEL study	{"effect":"SCCS/1625/20 Final Opinion Opinion on Benzophenone-3 (CAS No 131-57-7, EC No 205-031-5) _________________________________________________________________________________________________________________ 48 were 0. 187 µg/ml in females and 0.238 µg/mL in males. Twenty-four hours after the first application, the median BP-3 levels in plasma were 0.047 µg/ml in females and 0.041 µg/ml in males. This clearly shows that the levels of BP-3 had exceeded the concentration measured in rats at the NOAEL. 3.6 DISCUSSION The 2008 SCCP Opinion (SCCP/1201/08) had noted a number of shortcomings in the data provided as part of the dossier assessed in an earlier Opinion (SCCP/1069/06). Despite this, the SCS agrees with the SCCP Opinion (2008) that the submission provides a reasonably well- structured overview of the available test descriptions and publications. Physicochemical properties BP-3is a widely used UV filter in cosmetic products. It is an off-white to light-yellow powder with a melting point of 62°C to 65°","page":48,"pdf":"sccs_o_247.pdf","row_type":"noael_study","study_id":"sccs_o_247_noael_013"}
SCCS_vision_codex	NOAEL	=1000	mg/kg bw/day	rat	oral	Prenatal	developmental toxicity	{"citation":"Ref: 5, 33 in submission dossier OECD 414 GLP Rat Wistar CrI: WI (Han) Oral Gavage in corn oil 0, 40, 200 and 1000 mg/kg bw/day From GD5 to GD 19 observatio ns at GD 20 25 No adverse ef","dose":"Summary of the available in vivo studies on reproduction function and ED effects of BP-3 Number and reference Species Strain Model Routes Dose, Exposure period Group size Outcomes reported NOAEL/ LOAEL derived by the authors SCCS Comments General toxicity Reprotoxicity Teratogenicity ED related effects - 1- Prenatal developmen tal tox study Stud...","effect":"SCCS/1625/20 Final Opinion Opinion on Benzophenone-3 (CAS No 131-57-7, EC No 205-031-5) _________________________________________________________________________________________________________________ 62 Annex - 1: Summary of the available in vivo studies on reproduction function and ED effects of BP-3 Number and reference Species Strain Model Routes Dose, Exposure period Group size Outcomes reported NOAEL/ LOAEL derived by the authors SCCS Comments General toxicity Reprotoxicity Teratogenicity ED related effects - 1- Prenatal developmen tal tox study Study period: 2004. Ref: 5, 33 in submission dossier OECD 414 GLP Rat Wistar CrI: WI (Han) Oral Gavage in corn oil 0, 40, 200 and 1000 mg/kg bw/day From GD5 to GD 19 observatio ns at GD 20 25 No adverse effects in the dams no significant difference in the number of implantation sites/litter, mean resorptions/litt er, % litters with resorptions, number and weights of","page":62,"pdf":"sccs_o_247.pdf","row_type":"noael_study","study_id":"sccs_o_247_noael_018"}
SCCS_vision_codex	NOAEL	=200	mg/kg bw/d	rat	oral	-	developmental toxicity	{"citation":"Ref: 5, 33 in submission dossier OECD 414 GLP Rat Wistar CrI: WI (Han) Oral Gavage in corn oil 0, 40, 200 and 1000 mg/kg bw/day From GD5 to GD 19 observatio ns at GD 20 25 No adverse ef","dose":"WI (Han) Oral Gavage in corn oil 0, 40, 200 and 1000 mg/kg bw/day From GD5 to GD 19 observatio ns at GD 20 25 No adverse effects in the dams no significant difference in the number of implantation sites/litter, mean resorptions/litt er, % litters with resorptions, number and weights of live fetuses, between the control and treated groups No tera...","effect":"study Study period: 2004. Ref: 5, 33 in submission dossier OECD 414 GLP Rat Wistar CrI: WI (Han) Oral Gavage in corn oil 0, 40, 200 and 1000 mg/kg bw/day From GD5 to GD 19 observatio ns at GD 20 25 No adverse effects in the dams no significant difference in the number of implantation sites/litter, mean resorptions/litt er, % litters with resorptions, number and weights of live fetuses, between the control and treated groups No teratogenic effects Minor disturbance ad delay of ossification at 1000 mg/kg bw/day NOAEL mat. = 200 mg/kg bw/d NOAEL dev. = 200 mg/kg bw/d This study has been used in the previous SCCS opinion as the key study for calculation of the MOS. - 2 - Nakamura et al. 2015 Birth Defects Res 104: 35- 51 Study period: Rat Sprague- Dawley Food , 0, 1000, 3000, 10 000, 25 000, 50 000 ppm, i.e. around 67.9, 207.1, 670.8, 1798.3, 7-8 ↓ body weights of dams at 50 000 ppm at GD 10, 15 and 20; and at 25 000 ppm at GD15 ↓ organ (liver, kidney) weights (absolute no significant difference in the number of implantation si","page":62,"pdf":"sccs_o_247.pdf","row_type":"noael_study","study_id":"sccs_o_247_noael_019"}
SCCS_vision_codex	NOAEL	=0	ppm	-	-	-	reproductive toxicity	{"dose":"i.e. around 67.9, 207.1, 670.8, 1798.3, 7-8 ↓ body weights of dams at 50 000 ppm at GD 10, 15 and 20; and at 25 000 ppm at GD15 ↓ organ (liver, kidney) weights (absolute no significant difference in the number of implantation sites/litter, mean resorptions/litt er, % litters with resorptions, number and weights of live One foetus with hydrocepha...","effect":"i.e. around 67.9, 207.1, 670.8, 1798.3, 7-8 ↓ body weights of dams at 50 000 ppm at GD 10, 15 and 20; and at 25 000 ppm at GD15 ↓ organ (liver, kidney) weights (absolute no significant difference in the number of implantation sites/litter, mean resorptions/litt er, % litters with resorptions, number and weights of live One foetus with hydrocephaly at 50 000 ppm but no other malformations observed In male offspring at PND23: ↓ AGD in male at 50 000 ppm ↓ spermatocytes per seminiferous tubules at 3000 ppm and higher NOAEL : 3 000 ppm (670 mg/kg bw/day LOAEL : 10 000 ppm (1798 mg/kg/d) It would have been useful to have measured foetal testosterone as it is known that a decrease during specific windows of sensitivity in male foetuses mat impaired the development of reproductive","page":62,"pdf":"sccs_o_247.pdf","row_type":"noael_study","study_id":"sccs_o_247_noael_021"}
SCCS_vision_codex	NOAEL	=242	mg/kg bw/d	rat	oral	-	developmental toxicity	{"dose":"2012 (final report in 2015) Equivalent to OECD 414 GLP Rat Sprague- Dawley Oral Food 0, 3000, 10 000 and 30 000, ppm, i.e. around 242, 725 and 3689 mg/kg/ bw/day From GD 5 to GD 15 Observatio n at GD 15 25 .↓ body weights at 10 000 and 30 000 ppm and ↑ food consumption at 30 000 ppm modifications of blood biochemical factors at 30 000 ppm No eff...","effect":"SCCS-rejected applicant NOAEL: y) - 3 - Submission Ref 11 Study period: 2012 (final report in 2015) Equivalent to OECD 414 GLP Rat Sprague- Dawley Oral Food 0, 3000, 10 000 and 30 000, ppm, i.e. around 242, 725 and 3689 mg/kg/ bw/day From GD 5 to GD 15 Observatio n at GD 15 25 .↓ body weights at 10 000 and 30 000 ppm and ↑ food consumption at 30 000 ppm modifications of blood biochemical factors at 30 000 ppm No effects on foetuses, litters No teratogenic effects observed excepted increased skeletal variations not considered treatment related NOAEL mat. = 242 mg/kg bw/d NOAEL dev. = 3689 mg/kg bw/d SCCS agrees with the authors conclusion.","page":63,"pdf":"sccs_o_247.pdf","row_type":"noael_study","study_id":"sccs_o_247_noael_023"}
SCCS_vision_codex	NOAEL	=411	mg/kg/ day	rat	oral	39 days	NOAEL study	{"dose":"om GD6 during 39 days for F0 and then during 105 weeks for F1 Sacrifice at 14 weeks for 10 F1 rats ( m and f) at 0 and 10 000 ppm course of the study ↑ incidence of pigment in bone marrow at 10 000 ppm in m and f ↑ incidence of pigment in spleen at 10 000 ppm in m and f ↑ incidence of syncytial alteration in the liver of males at all doses ↑ inc...","effect":"om GD6 during 39 days for F0 and then during 105 weeks for F1 Sacrifice at 14 weeks for 10 F1 rats ( m and f) at 0 and 10 000 ppm course of the study ↑ incidence of pigment in bone marrow at 10 000 ppm in m and f ↑ incidence of pigment in spleen at 10 000 ppm in m and f ↑ incidence of syncytial alteration in the liver of males at all doses ↑ incidence of renal alterations at 3000 and 10 000 ppm in males ↑ incidence of osseous metaplasia in females at 10 000 ppm - 6 - Rats Oral Food 0, 3125,625,1 in males: NOAEL = 411 mg/kg/ day","page":65,"pdf":"sccs_o_247.pdf","row_type":"noael_study","study_id":"sccs_o_247_noael_028"}
SCCS_vision_codex	NOAEL	=100	mg/kg bw/day	rat	oral	Sub-chronic	repeated dose toxicity	{"dose":"at 3458 mg/kg bw/day In females: ↑ estrous cycle length in female rats at 3458 mg/kg bw/day based on effects in the kidney - 7 - Ref 7, 16, 33 in submission dossier Sub-chronic toxicity study OECD 408 Non GLP Rats Oral Food 0, 0, 0.02, 0.1, 0.5 and 1% in the diet ie ± 0, 20, 100, 500 and 1000 mg/kg bw/day 13 weeks In males and females: ↓ in abso...","effect":"at 3458 mg/kg bw/day In females: ↑ estrous cycle length in female rats at 3458 mg/kg bw/day based on effects in the kidney - 7 - Ref 7, 16, 33 in submission dossier Sub-chronic toxicity study OECD 408 Non GLP Rats Oral Food 0, 0, 0.02, 0.1, 0.5 and 1% in the diet ie ± 0, 20, 100, 500 and 1000 mg/kg bw/day 13 weeks In males and females: ↓ in absolute weights of adrenal gland, pituitary gland and gonads at 1000 mg/kg bw/day ↑ in relative thyroid and pituitary and adrenal weights at 500 and 1000 mg/kg bw/day NOAEL = 100 mg/kg bw/day","page":66,"pdf":"sccs_o_247.pdf","row_type":"noael_study","study_id":"sccs_o_247_noael_029"}
SCCS_vision_codex	NOAEL	=1246	mg/kg bw /day	rat	oral	Sub-chronic	repeated dose toxicity	{"dose":"___________________________________________________________________________________________________ 67 - 8 - Ref 5, 7, 33 in submission dossier Sub-chronic toxicity study OECD 408 GLP Mice Oral Food 0, 3125,6250, 12500, 25000 and 50000 ppm , ie ± 0, 554, 1246, 2860, 6780 and 16238 mg/kg bw/day 13 weeks No effects on reproductive parameters at 67...","effect":"___________________________________________________________________________________________________ 67 - 8 - Ref 5, 7, 33 in submission dossier Sub-chronic toxicity study OECD 408 GLP Mice Oral Food 0, 3125,6250, 12500, 25000 and 50000 ppm , ie ± 0, 554, 1246, 2860, 6780 and 16238 mg/kg bw/day 13 weeks No effects on reproductive parameters at 6780 mg/kg bw/day or below Males: ↓ in sperm density and ↑ in abnormal sperm morphology at 16238 mg/kg bw/day Females: ↑ in estrous cycles length at 16238 mg/kg bw/day NOAEL = 1246 mg/kg bw /day based on systemic effects -9- Ref 21 Sub-chronic toxicity study GLP Rats 0 and 10000 ppm ie ± 585/632 mg/kg bw/day in males and females Estrogen- responsive genes showed no change in response to BP- 3 in transcriptome analysis -10- Ref 5, 7, 33 in submission dossier Sub-chronic toxicity study ± OECD 411 GLP Rats Dermal 0, 12.5, 25, 50, 100 and 200 mg/kg bw/day 13 weeks No effects on reproductive parameters NOAEL = 200 mg/kg bw/day -11- Mice Dermal 0, 22.8, 45.5, 91, ↓ in epi","page":67,"pdf":"sccs_o_247.pdf","row_type":"noael_study","study_id":"sccs_o_247_noael_030"}
SCCS_vision_codex	NOAEL	=364	mg/kg bw/day	rat	dermal	Sub-chronic	repeated dose toxicity	{"dose":"based on systemic effects -9- Ref 21 Sub-chronic toxicity study GLP Rats 0 and 10000 ppm ie ± 585/632 mg/kg bw/day in males and females Estrogen- responsive genes showed no change in response to BP- 3 in transcriptome analysis -10- Ref 5, 7, 33 in submission dossier Sub-chronic toxicity study ± OECD 411 GLP Rats Dermal 0, 12.5, 25, 50, 100 and 2...","effect":"based on systemic effects -9- Ref 21 Sub-chronic toxicity study GLP Rats 0 and 10000 ppm ie ± 585/632 mg/kg bw/day in males and females Estrogen- responsive genes showed no change in response to BP- 3 in transcriptome analysis -10- Ref 5, 7, 33 in submission dossier Sub-chronic toxicity study ± OECD 411 GLP Rats Dermal 0, 12.5, 25, 50, 100 and 200 mg/kg bw/day 13 weeks No effects on reproductive parameters NOAEL = 200 mg/kg bw/day -11- Mice Dermal 0, 22.8, 45.5, 91, ↓ in epididymal sperm density NOAEL = 364 mg/kg bw/day In view of the effects on sperm","page":67,"pdf":"sccs_o_247.pdf","row_type":"noael_study","study_id":"sccs_o_247_noael_032"}
SCCS_vision_codex	NOAEL	=3	-	-	-	-	NOAEL study	{"dose":"Products | Conc. | Surface | Systemic Exposure Dose (SED) mg/kg bw/d | NOAEL* | MOS","effect":"Table 3: Calculation of Margin of Safety for different products containing BP-3: Products | Conc. | Surface | Systemic Exposure Dose (SED) mg/kg bw/d | NOAEL* | MOS","page":47,"pdf":"sccs_o_247.pdf","row_type":"noael_study","study_id":"sccs_o_247_noael_033"}
SCCS_vision_codex	NOAEL	=0.5	%	-	-	-	NOAEL study	{"effect":"Table 3: Calculation of Margin of Safety for different products containing BP-3: Non-UV** | 0.50% | whole body | 0.116 | 0 | 0 | 0.116 | 67.9 | 585","page":47,"pdf":"sccs_o_247.pdf","row_type":"noael_study","study_id":"sccs_o_247_noael_039"}
SCCS_vision_codex	NOAEL	=62	-	-	-	-	NOAEL study	{"dose":"Number and reference | Species Strain Model | Routes | Dose, Exposure period | Group size | Outcomes reported | NOAEL/ LOAEL derived by the authors | SCCS Comments","effect":"Unlabeled table on page 62: Number and reference | Species Strain Model | Routes | Dose, Exposure period | Group size | Outcomes reported | NOAEL/ LOAEL derived by the authors | SCCS Comments","page":62,"pdf":"sccs_o_247.pdf","row_type":"noael_study","study_id":"sccs_o_247_noael_041"}
SCCS_vision_codex	NOAEL	=3448.2	mg/kg/day	-	-	-	NOAEL study	{"dose":"Unlabeled table on page 63: and 3448.2 mg/kg/day . from GD6 to PND 23 Observatio n on PND1 and PND 23 | and relative) in female and male offspring and blood biochemical factors in the high dose (≥10,000 ppm) groups | fetuses, or sex ratios between the control and treated groups; ↑ ovaries and uterine weights (absolute and relative) at 1000 ppm b...","effect":"Unlabeled table on page 63: and 3448.2 mg/kg/day . from GD6 to PND 23 Observatio n on PND1 and PND 23 | and relative) in female and male offspring and blood biochemical factors in the high dose (≥10,000 ppm) groups | fetuses, or sex ratios between the control and treated groups; ↑ ovaries and uterine weights (absolute and relative) at 1000 ppm but not at higher doses | doses (dose related) ↑ apoptic cells in seminiferous tubules at 10 000 ppm and above (not dose related) Limited ↓ testo level at 3000 and 25 000 ppm In female offspring at PND23 Delayed follicular development at 10 000 and 50 000 ppm | system (↓ AGD, ↓ spermatocytes production and/or quality…) Due to the effects on the ↓ of spermatocyte which may be due to an ED effects of BP-3 SCCS considered 3000 ppm as a LOAEL and therefore the NOAEL should be 1000 ppm ( 68 mg /kg bw/day)","page":63,"pdf":"sccs_o_247.pdf","row_type":"noael_study","study_id":"sccs_o_247_noael_045"}
SCCS_vision_codex	NOAEL	=3689	mg/kg	rat	oral	-	developmental toxicity	{"dose":"2012 (final report in 2015) Equivalent to OECD 414 GLP | Rat Sprague- Dawley | Oral Food | 0, 3000, 10 000 and 30 000, ppm, i.e. around 242, 725 and 3689 mg/kg/ bw/day From GD 5 to GD 15 Observatio n at GD 15 | 25 | .↓ body weights at 10 000 and 30 000 ppm and ↑ food consumption at 30 000 ppm modifications of blood biochemical factors at 30 000...","effect":"SCCS-rejected applicant NOAEL: Unlabeled table on page 63: - 3 - Submission Ref 11 Study period: 2012 (final report in 2015) Equivalent to OECD 414 GLP | Rat Sprague- Dawley | Oral Food | 0, 3000, 10 000 and 30 000, ppm, i.e. around 242, 725 and 3689 mg/kg/ bw/day From GD 5 to GD 15 Observatio n at GD 15 | 25 | .↓ body weights at 10 000 and 30 000 ppm and ↑ food consumption at 30 000 ppm modifications of blood biochemical factors at 30 000 ppm | No effects on foetuses, litters | No teratogenic effects observed excepted increased skeletal variations not considered treatment related | NOAEL mat. = 242 mg/kg bw/d NOAEL dev. = 3689 mg/kg bw/d | SCCS agrees with the authors conclusion.","page":63,"pdf":"sccs_o_247.pdf","row_type":"noael_study","study_id":"sccs_o_247_noael_046"}
SCCS_vision_codex	NOAEL	=660	mg/kg	rat	oral	105 weeks	developmental toxicity	{"dose":"2010-2012 (final report in 2020) Ref 21 in submission dossier GLP | Rat Sprague- Dawley | Oral Food | 0,1000,300 0and 10 000, ppm, i.e. ± 70, 206 and 660 mg/kg/ bw/day during gestation and 157, 478 and 1609 mg/kg bw/day during lactation . from GD6 until PND 21 for F0 and then during 105 weeks for F1 observatio n at PND1, 4, 7 , 14 and 21 | 35-42...","effect":"Unlabeled table on page 64: - 4 - NTP modified 1- gen study equivalent to perinatal developmen tal tox study Study period : 2010-2012 (final report in 2020) Ref 21 in submission dossier GLP | Rat Sprague- Dawley | Oral Food | 0,1000,300 0and 10 000, ppm, i.e. ± 70, 206 and 660 mg/kg/ bw/day during gestation and 157, 478 and 1609 mg/kg bw/day during lactation . from GD6 until PND 21 for F0 and then during 105 weeks for F1 observatio n at PND1, 4, 7 , 14 and 21 | 35-42 femal es for F0 and 50-60 for F1 (m and f) | At 10 000 ppm: ↓ body weights gain in F0 at GD6- 9 and lactation day 4-21 At 3000 ppm: ↓ body weights gain in F0 at GD 18 -21 ↓ body weights of F1 m and f at 10 000 ppm over the course of the study and at 3000 ppm in f at week 77 | No effects on number of pups, litter size, sex distribution, In female F1: ↑ stromal polyp and endometrium hyperplasia ppm in the uterus at 3000 In male F1: ↑ fibirnoid necrosis of the arterioles at 10 000 ppm at the end of the 2 years | No teratogenic effects except at the highest dose: skeletal aberrations in the presence of maternal toxicity |...","page":64,"pdf":"sccs_o_247.pdf","row_type":"noael_study","study_id":"sccs_o_247_noael_048"}
SCCS_vision_codex	NOAEL	=1	%	rat	oral	Sub-chronic	repeated dose toxicity	{"dose":"Unlabeled table on page 66: - 7 - Ref 7, 16, 33 in submission dossier Sub-chronic toxicity study OECD 408 Non GLP | Rats | Oral Food | 0, 0, 0.02, 0.1, 0.5 and 1% in the diet ie ± 0, 20, 100, 500 and 1000 mg/kg bw/day 13 weeks | In males and females: ↓ in absolute weights of adrenal gland, pituitary gland and gonads at 1000 mg/kg bw/day ↑ in rel...","effect":"Unlabeled table on page 66: - 7 - Ref 7, 16, 33 in submission dossier Sub-chronic toxicity study OECD 408 Non GLP | Rats | Oral Food | 0, 0, 0.02, 0.1, 0.5 and 1% in the diet ie ± 0, 20, 100, 500 and 1000 mg/kg bw/day 13 weeks | In males and females: ↓ in absolute weights of adrenal gland, pituitary gland and gonads at 1000 mg/kg bw/day ↑ in relative thyroid and pituitary and adrenal weights at 500 and 1000 mg/kg bw/day | NOAEL = 100 mg/kg bw/day","page":66,"pdf":"sccs_o_247.pdf","row_type":"noael_study","study_id":"sccs_o_247_noael_050"}
SCCS_vision_codex	NOAEL	=50000	ppm	mouse	oral	Sub-chronic	repeated dose toxicity	{"dose":"Unlabeled table on page 67: - 8 - Ref 5, 7, 33 in submission dossier Sub-chronic toxicity study OECD 408 GLP | Mice | Oral Food | 0, 3125,6250, 12500, 25000 and 50000 ppm , ie ± 0, 554, 1246, 2860, 6780 and 16238 mg/kg bw/day 13 weeks | No effects on reproductive parameters at 6780 mg/kg bw/day or below | Males: ↓ in sperm density and ↑ in abnor...","effect":"Unlabeled table on page 67: - 8 - Ref 5, 7, 33 in submission dossier Sub-chronic toxicity study OECD 408 GLP | Mice | Oral Food | 0, 3125,6250, 12500, 25000 and 50000 ppm , ie ± 0, 554, 1246, 2860, 6780 and 16238 mg/kg bw/day 13 weeks | No effects on reproductive parameters at 6780 mg/kg bw/day or below | Males: ↓ in sperm density and ↑ in abnormal sperm morphology at 16238 mg/kg bw/day Females: ↑ in estrous cycles length at 16238 mg/kg bw/day | NOAEL = 1246 mg/kg bw /day based on systemic effects","page":67,"pdf":"sccs_o_247.pdf","row_type":"noael_study","study_id":"sccs_o_247_noael_052"}

ToxValDB_ECHA_IUCLID 8 endpoints

Source	Endpoint Type	Value	Unit	Species	Route	Duration	Study Type	Reference
ToxValDB_ECHA_IUCLID	NOAEL	>10000	ppm	Rat	oral	short-term; 27 days	short-term	QUALITY=2 (reliable with restrictions); STORED_SOURCE_RECORD=https://clowder.edap-cluster.com/files/66a7ca69e4b0a7c65d221a56; RECORD_SOURCE_LEVEL=Extraction document; SOURCE_URL=https://echa.europa.eu/; SUBSOURCE_URL=https://echa.europa.eu/registration-dossier/-/registered-dossier/5515/7/6/2?documentUUID=e7b04d41-830e-4bd4-af6e-66e562fe15b4; YEAR=2011; ORIGINAL_YEAR=2011; STUDY_GROUP=ECHA IUCLID:15835167:M:--; QC_CATEGORY=Programmatically extracted from structured data source; Source overall passed QC, but this record was not manually checked; QC_STATUS=not determined; SOURCE_HASH=ToxValhc_767c37c1bd95d03e2ae9579d47350db0
ToxValDB_ECHA_IUCLID	NOAEL	>789	mg/kg bw/day	Rat	oral	short-term; 27 days	short-term	QUALITY=2 (reliable with restrictions); STORED_SOURCE_RECORD=https://clowder.edap-cluster.com/files/66a7ca69e4b0a7c65d221a56; RECORD_SOURCE_LEVEL=Extraction document; SOURCE_URL=https://echa.europa.eu/; SUBSOURCE_URL=https://echa.europa.eu/registration-dossier/-/registered-dossier/5515/7/6/2?documentUUID=e7b04d41-830e-4bd4-af6e-66e562fe15b4; YEAR=2011; ORIGINAL_YEAR=2011; STUDY_GROUP=ECHA IUCLID:15850650:M:--; QC_CATEGORY=Programmatically extracted from structured data source; Source overall passed QC, and this record was expert reviewed; QC_STATUS=pass; SOURCE_HASH=ToxValhc_6811ec250812d5358553c3b1711c66d8
ToxValDB_ECHA_IUCLID	NOAEL	=600	mg/kg bw/day	Rat	oral	subchronic; 13 weeks	subchronic	QUALITY=1 (reliable without restriction); STORED_SOURCE_RECORD=https://clowder.edap-cluster.com/files/669ead33e4b0a7c65d1c304d; RECORD_SOURCE_LEVEL=Extraction document; SOURCE_URL=https://echa.europa.eu/; SUBSOURCE_URL=https://echa.europa.eu/registration-dossier/-/registered-dossier/5515/7/6/2?documentUUID=e7b04d41-830e-4bd4-af6e-66e562fe15b4; YEAR=2011; ORIGINAL_YEAR=2011; STUDY_GROUP=ECHA IUCLID:15850651:M/F:--; QC_CATEGORY=Programmatically extracted from structured data source; Source overall passed QC, and this record was expert reviewed; QC_STATUS=pass; SOURCE_HASH=ToxValhc_6c1260d8e057cb744df8d475fdba0e59
ToxValDB_ECHA_IUCLID	NOAEL	=393	mg/kg bw/day	Rat	oral	subchronic; 13 weeks	subchronic	QUALITY=1 (reliable without restriction); STORED_SOURCE_RECORD=https://clowder.edap-cluster.com/files/669ead33e4b0a7c65d1c304d; RECORD_SOURCE_LEVEL=Extraction document; SOURCE_URL=https://echa.europa.eu/; SUBSOURCE_URL=https://echa.europa.eu/registration-dossier/-/registered-dossier/5515/7/6/2?documentUUID=e7b04d41-830e-4bd4-af6e-66e562fe15b4; YEAR=2011; ORIGINAL_YEAR=2011; STUDY_GROUP=ECHA IUCLID:15850652:F:--; QC_CATEGORY=Programmatically extracted from structured data source; Source overall passed QC, and this record was expert reviewed; QC_STATUS=pass; SOURCE_HASH=ToxValhc_a667354982ca24b01f6534f6d59b3c10
ToxValDB_ECHA_IUCLID	NOAEL	=429	mg/kg bw/day	Rat	oral	subchronic; 13 weeks	subchronic	QUALITY=1 (reliable without restriction); STORED_SOURCE_RECORD=https://clowder.edap-cluster.com/files/669ead33e4b0a7c65d1c304d; RECORD_SOURCE_LEVEL=Extraction document; SOURCE_URL=https://echa.europa.eu/; SUBSOURCE_URL=https://echa.europa.eu/registration-dossier/-/registered-dossier/5515/7/6/2?documentUUID=e7b04d41-830e-4bd4-af6e-66e562fe15b4; YEAR=2011; ORIGINAL_YEAR=2011; STUDY_GROUP=ECHA IUCLID:15850653:M:--; QC_CATEGORY=Programmatically extracted from structured data source; Source overall passed QC, and this record was expert reviewed; QC_STATUS=pass; SOURCE_HASH=ToxValhc_dc9aea22ca3983a3175428700d2ff737
ToxValDB_ECHA_IUCLID	NOAEL	=4925	mg/kg bw/day	Mouse	oral	subchronic; 13 weeks	subchronic	QUALITY=1 (reliable without restriction); STORED_SOURCE_RECORD=https://clowder.edap-cluster.com/files/669ead33e4b0a7c65d1c3050; RECORD_SOURCE_LEVEL=Extraction document; SOURCE_URL=https://echa.europa.eu/; SUBSOURCE_URL=https://echa.europa.eu/registration-dossier/-/registered-dossier/5515/7/6/2?documentUUID=e7b04d41-830e-4bd4-af6e-66e562fe15b4; YEAR=2011; ORIGINAL_YEAR=2011; STUDY_GROUP=ECHA IUCLID:15850654:M/F:--; QC_CATEGORY=Programmatically extracted from structured data source; Source overall passed QC, and this record was expert reviewed; QC_STATUS=pass; SOURCE_HASH=ToxValhc_7e08df1eea20582b9035b4c2a3b0cd6f
ToxValDB_ECHA_IUCLID	NOAEL	=7579	mg/kg bw/day	Mouse	oral	subchronic; 13 weeks	subchronic	QUALITY=1 (reliable without restriction); STORED_SOURCE_RECORD=https://clowder.edap-cluster.com/files/669ead33e4b0a7c65d1c3050; RECORD_SOURCE_LEVEL=Extraction document; SOURCE_URL=https://echa.europa.eu/; SUBSOURCE_URL=https://echa.europa.eu/registration-dossier/-/registered-dossier/5515/7/6/2?documentUUID=e7b04d41-830e-4bd4-af6e-66e562fe15b4; YEAR=2011; ORIGINAL_YEAR=2011; STUDY_GROUP=ECHA IUCLID:15850655:F:--; QC_CATEGORY=Programmatically extracted from structured data source; Source overall passed QC, and this record was expert reviewed; QC_STATUS=pass; SOURCE_HASH=ToxValhc_20c705263e774accec97f436e472819d
ToxValDB_ECHA_IUCLID	NOAEL	=5981	mg/kg bw/day	Mouse	oral	subchronic; 13 weeks	subchronic	QUALITY=1 (reliable without restriction); STORED_SOURCE_RECORD=https://clowder.edap-cluster.com/files/669ead33e4b0a7c65d1c3050; RECORD_SOURCE_LEVEL=Extraction document; SOURCE_URL=https://echa.europa.eu/; SUBSOURCE_URL=https://echa.europa.eu/registration-dossier/-/registered-dossier/5515/7/6/2?documentUUID=e7b04d41-830e-4bd4-af6e-66e562fe15b4; YEAR=2011; ORIGINAL_YEAR=2011; STUDY_GROUP=ECHA IUCLID:15850656:M:--; QC_CATEGORY=Programmatically extracted from structured data source; Source overall passed QC, and this record was expert reviewed; QC_STATUS=pass; SOURCE_HASH=ToxValhc_32b4ce8e63b41de2d12324a7c65e536c

ToxValDB_GESTIS_DNEL 1 endpoint

Source	Endpoint Type	Value	Unit	Species	Route	Duration	Study Type	Reference
ToxValDB_GESTIS_DNEL	DNEL systemic	=27.7	mg/m3	Human	inhalation	-	Toxicity Value	STORED_SOURCE_RECORD=https://clowder.edap-cluster.com/files/6543dd69e4b045b9ff7cd87e; RECORD_SOURCE_LEVEL=Extraction document; SOURCE_URL=https://www.dguv.de/ifa/gestis/gestis-dnel-liste/index-2.jsp; STUDY_GROUP=GESTIS DNEL:15633959:-:--; QC_CATEGORY=Programmatically extracted from structured data source; Source overall passed QC, but this record was not manually checked; QC_STATUS=not determined; SOURCE_HASH=ToxValhc_7a71ec5d07c09482ac06ec86042c641f

ToxValDB_HESS 2 endpoints

Source	Endpoint Type	Value	Unit	Species	Route	Duration	Study Type	Reference
ToxValDB_HESS	NOEL	<213	mg/kg bw/day	Rat	oral	-	subchronic	STORED_SOURCE_RECORD=https://clowder.edap-cluster.com/files/60da0e16e4b0a676289df6d2; RECORD_SOURCE_LEVEL=Extraction document; SOURCE_URL=https://www.nite.go.jp/en/chem/qsar/hess_update-e.html; TOXICOLOGICAL_EFFECT=Hematology: Plt increase|Absolute Organ Weight: Liver increase|Relative Organ Weight: Liver increase; TOXICOLOGICAL_EFFECT_CATEGORY=hematology|organ weight; STUDY_GROUP=HESS:15638244:M:--; QC_CATEGORY=Programmatically extracted from structured data source; Source overall passed QC, and this record was expert reviewed; QC_STATUS=pass; SOURCE_HASH=ToxValhc_47457fc99ba4bb8e70a0daa42874eb00
ToxValDB_HESS	NOEL	<196	mg/kg bw/day	Rat	oral	-	subchronic	STORED_SOURCE_RECORD=https://clowder.edap-cluster.com/files/60da0e16e4b0a676289df6d2; RECORD_SOURCE_LEVEL=Extraction document; SOURCE_URL=https://www.nite.go.jp/en/chem/qsar/hess_update-e.html; TOXICOLOGICAL_EFFECT=Hematology: Hgb decrease|Blood Chemistry: gamma-GTP increase|Absolute Organ Weight: Liver increase, Thymus decrease|Relative Organ Weight: Liver increase, Thymus decrease; TOXICOLOGICAL_EFFECT_CATEGORY=clinical chemistry|hematology|organ weight; STUDY_GROUP=HESS:15638946:F:--; QC_CATEGORY=Programmatically extracted from structured data source; Source overall passed QC, and this record was expert reviewed; QC_STATUS=pass; SOURCE_HASH=ToxValhc_5dacb3a11e482c31b6c87669778b3749

ToxValDB_Uterotrophic_Hershberger_DB 1 endpoint

Source	Endpoint Type	Value	Unit	Species	Route	Duration	Study Type	Reference
ToxValDB_Uterotrophic_Hershberger_DB	LEL	=1525	mg/kg bw/day	Rat	oral	short-term; 4 days	uterotrophic	LONG_REF=Kleinstreuer et al., A Curated Database of Rodent Uterotrophic Bioactivity, EHP Vol 124 2106, https://doi.org/10.1289/ehp.1510183; TITLE=A Curated Database of Rodent Uterotrophic Bioactivity; AUTHOR=Kleinstreuer et al., A Curated Database of Rodent Uterotrophic Bioactivity, EHP Vol 124; DOI=10.1289/ehp.1510183; GUIDELINE=0; STORED_SOURCE_RECORD=https://clowder.edap-cluster.com/files/6759abc7e4b0a7c65d37b40c; RECORD_SOURCE_LEVEL=Extraction document; TOXICOLOGICAL_EFFECT=Active; TOXICOLOGICAL_EFFECT_CATEGORY=other; STUDY_GROUP=Uterotrophic Hershberger DB:15713690:-:--; QC_CATEGORY=Programmatically extracted from structured data source; Source overall passed QC, but this record was not manually checked; QC_STATUS=not determined; SOURCE_HASH=ToxValhc_eb8cddbb65976e65b3a41d8e79f3b95b

UnifiedCodex:SCCS_SHADOW:beta.noael_studies 162 endpoints

Source	Endpoint Type	Value	Unit	Species	Route	Duration	Study Type	Reference
UnifiedCodex:SCCS_SHADOW:beta.noael_studies	-	311	mg/kg bw/day	rat	oral	14d	-	SOURCE_SUBDIR=sccp_o_078; REPORT_TITLE=OPINION ON BENZOPHENONE-3 COLIPA N° S38; OPINION_NUMBER=SCCP/1069/06; COMMITTEE=SCCP; REPORT_DATE=19 December 2006; VALUE_TEXT=311; DOSE=2,238 mg/kg bw/day: increased liver weights in males and females associated with the presence of cytoplasmic vacuolisation of hepatocytes; increased kidney weights in males 3,868 mg/kg bw/day: reduced feed consumption in males and females; reduced body weight gain in males; increased liver weights in males and females associated with the presenc...; EFFECT=2,238 mg/kg bw/day: increased liver weights in males and females associated with the presence of cytoplasmic vacuolisation of hepatocytes; increased kidney weights in males 3,868 mg/kg bw/day: reduced feed consumption in males and females; reduced body weight gain in males; increased liver weights in males and females associated with the presence of cytoplasmic vacuolisation of hepatocytes; increased kidney weights in males; focal dilatation of renal tubules in the cortex and/or medulla Study authors' conclusion: NOAEL (14d-oral) = 295/311 mg/kg bw/day for the male/female rat. Ref.: 30 14-day oral toxicity in mouse (1985-88) Benzophenone-3 was administered in the diet to five B6C3F1 mice per sex and group at concentrations of 0, 3,125; 6,250; 12,500; 25,000 and 50,000 ppm for 2 weeks. The dietary test substance preparations were analyzed for stability and proved to be stable in the diet for at least 3 weeks. Clinical examinations covering clinical signs, mortality, body weight and food consumption were performed in all animals; CITATION=Ref.: 30 14-day oral toxicity in mouse (1985-88) Benzophenone-3 was administered in the diet to five B6C3F1 mice per sex and group at concentrations of 0, 3,125; CITATION_NUMBERS=[30,14,1985,88,3,6,1,125]; REFERENCE=Ref.: 30 14-day oral toxicity in mouse (1985-88) Benzophenone-3 was administered in the diet to five B6C3F1 mice per sex and group at concentrations of 0, 3,125; DETAILS_JSON={"cas_number":"131-57-7","citation":"Ref.: 30 14-day oral toxicity in mouse (1985-88) Benzophenone-3 was administered in the diet to five B6C3F1 mice per sex and group at concentrations of 0, 3,125","dose":"2,238 mg/kg bw/day: increased liver weights in males and females associated with the presence of cytoplasmic vacuolisation of hepatocytes; increased kidney weights in males 3,868 mg/kg bw/day: reduced feed consumption in males and females; reduced body weight gain in males; increased liver weights in males and females associated with the presenc...","duration":"14d","effect":"2,238 mg/kg bw/day: increased liver weights in males and females associated with the presence of cytoplasmic vacuolisation of hepatocytes; increased kidney weights in males 3,868 mg/kg bw/day: reduced feed consumption in males and females; reduced body weight gain in males; increased liver weights in males and females associated with the presence of cytoplasmic vacuolisation of hepatocytes; increased kidney weights in males; focal dilatation of renal tubules in the cortex and/or medulla Study authors' conclusion: NOAEL (14d-oral) = 295/311 mg/kg bw/day for the male/female rat. Ref.: 30 14-day oral toxicity in mouse (1985-88) Benzophenone-3 was administered in the diet to five B6C3F1 mice per sex and group at concentrations of 0, 3,125; 6,250; 12,500; 25,000 and 50,000 ppm for 2 weeks. The dietary test substance preparations were analyzed for stability and proved to be stable in the diet for at least 3 weeks. Clinical examinations covering clinical signs, mortality, body weight and food consumption were performed in all animals","endpoint":"","ingredient":"INCI name","loael_value":"","noael_unit":"mg/kg bw/day","noael_value":"311","page":12,"route":"oral","species":"rat","study_id":"sccp_o_078_noael_001"}
UnifiedCodex:SCCS_SHADOW:beta.noael_studies	-	140	mg/kg bw/day	rat	oral	14d	-	SOURCE_SUBDIR=sccp_o_078; REPORT_TITLE=OPINION ON BENZOPHENONE-3 COLIPA N° S38; OPINION_NUMBER=SCCP/1069/06; COMMITTEE=SCCP; REPORT_DATE=19 December 2006; VALUE_TEXT=140; DOSE=7.0 mg/kg bw/day: no adverse effects noted 13.6 mg/kg bw/day: no adverse effects noted 27.7 mg/kg bw/day: slightly increased liver weights in females 54.9 mg/kg bw/day: slightly increased liver weights in female 110 mg/kg bw/day: slightly increased liver weights in females; slightly increased kidney weights Study authors' conclusion:; EFFECT=ficed and macroscopically examined, organs were weighed and comprehensive histopathology was performed. The following effects were noted (dietary levels were converted to dosages): 7.0 mg/kg bw/day: no adverse effects noted 13.6 mg/kg bw/day: no adverse effects noted 27.7 mg/kg bw/day: slightly increased liver weights in females 54.9 mg/kg bw/day: slightly increased liver weights in female 110 mg/kg bw/day: slightly increased liver weights in females; slightly increased kidney weights Study authors' conclusion: NOAEL (14d-dermal) = 100/140 mg/kg bw/day for the male/female rat. Ref.: 30 28-day dermal toxicity in rat (1985-88) A publication of 1995 describes how 6 male Sprague-Dawley rats per group received Benzophenone-3, formulated in petroleum jelly base, at dosage levels of 0 and 100 mg/kg bw/day, twice daily for 4 weeks. Clinical examinations covering clinical signs and body weight were performed in all animals. Blood samples for haematology and clinical chemistry were taken prior to the start of treatment and on day 16.; CITATION=Ref.: 30 28-day dermal toxicity in rat (1985-88) A publication of 1995 describes how 6 male Sprague-Dawley rats per group received Benzophenone-3, formulated in petroleum jelly base, at; CITATION_NUMBERS=[30,28,1985,88,1995,6,3]; REFERENCE=Ref.: 30 28-day dermal toxicity in rat (1985-88) A publication of 1995 describes how 6 male Sprague-Dawley rats per group received Benzophenone-3, formulated in petroleum jelly base, at; DETAILS_JSON={"cas_number":"131-57-7","citation":"Ref.: 30 28-day dermal toxicity in rat (1985-88) A publication of 1995 describes how 6 male Sprague-Dawley rats per group received Benzophenone-3, formulated in petroleum jelly base, at","dose":"7.0 mg/kg bw/day: no adverse effects noted 13.6 mg/kg bw/day: no adverse effects noted 27.7 mg/kg bw/day: slightly increased liver weights in females 54.9 mg/kg bw/day: slightly increased liver weights in female 110 mg/kg bw/day: slightly increased liver weights in females; slightly increased kidney weights Study authors' conclusion:","duration":"14d","effect":"ficed and macroscopically examined, organs were weighed and comprehensive histopathology was performed. The following effects were noted (dietary levels were converted to dosages): 7.0 mg/kg bw/day: no adverse effects noted 13.6 mg/kg bw/day: no adverse effects noted 27.7 mg/kg bw/day: slightly increased liver weights in females 54.9 mg/kg bw/day: slightly increased liver weights in female 110 mg/kg bw/day: slightly increased liver weights in females; slightly increased kidney weights Study authors' conclusion: NOAEL (14d-dermal) = 100/140 mg/kg bw/day for the male/female rat. Ref.: 30 28-day dermal toxicity in rat (1985-88) A publication of 1995 describes how 6 male Sprague-Dawley rats per group received Benzophenone-3, formulated in petroleum jelly base, at dosage levels of 0 and 100 mg/kg bw/day, twice daily for 4 weeks. Clinical examinations covering clinical signs and body weight were performed in all animals. Blood samples for haematology and clinical chemistry were taken prior to the start of treatment and on day 16.","endpoint":"","ingredient":"INCI name","loael_value":"","noael_unit":"mg/kg bw/day","noael_value":"140","page":13,"route":"oral","species":"rat","study_id":"sccp_o_078_noael_003"}
UnifiedCodex:SCCS_SHADOW:beta.noael_studies	-	=100	mg/kg bw/day	rat	oral	12 weeks	-	SOURCE_SUBDIR=sccp_o_078; REPORT_TITLE=OPINION ON BENZOPHENONE-3 COLIPA N° S38; OPINION_NUMBER=SCCP/1069/06; COMMITTEE=SCCP; REPORT_DATE=19 December 2006; VALUE_TEXT== 100; DOSE=NOEL (90d-oral) = 100 mg/kg bw/day for male and female rats.; EFFECT=males; anaemia, lymphocytosis and reduced number of granulocytes after 12 weeks in females; decreased absolute weights of the thymus, heart, pituitary gland, lungs, spleen, adrenal glands, and gonads in males and females; decreased relative weights of the pituitary gland, thymus, heart and adrenal glands in males and females; decreased relative weights of the lungs and spleen in females; increased relative thyroid weight in females; degenerative nephritis in kidneys of males and females Study authors' conclusion: NOEL (90d-oral) = 100 mg/kg bw/day for male and female rats. Ref.: 44 90-day oral toxicity in rat (2) (1985-1988) Ten F344/N rats per sex and group received Benzophenone-3 in concentrations of 0; 3,125; 6,250; 12,500; 25,000 and 50,000 ppm in the diet for 13 weeks. The dietary test substance preparations were analyzed for stability and proved to be stable in the diet for at least 3 weeks. Clinical examinations covering clinical signs, mortality, body weight and food consumption were performed in all animals at regula; CITATION=Ref.: 44 90-day oral toxicity in rat (2) (1985-1988) Ten F344/N rats per sex and group received Benzophenone-3 in concentrations of 0; CITATION_NUMBERS=[44,90,2,1985,1988,344,3]; REFERENCE=Ref.: 44 90-day oral toxicity in rat (2) (1985-1988) Ten F344/N rats per sex and group received Benzophenone-3 in concentrations of 0; DETAILS_JSON={"cas_number":"131-57-7","citation":"Ref.: 44 90-day oral toxicity in rat (2) (1985-1988) Ten F344/N rats per sex and group received Benzophenone-3 in concentrations of 0","dose":"NOEL (90d-oral) = 100 mg/kg bw/day for male and female rats.","duration":"12 weeks","effect":"males; anaemia, lymphocytosis and reduced number of granulocytes after 12 weeks in females; decreased absolute weights of the thymus, heart, pituitary gland, lungs, spleen, adrenal glands, and gonads in males and females; decreased relative weights of the pituitary gland, thymus, heart and adrenal glands in males and females; decreased relative weights of the lungs and spleen in females; increased relative thyroid weight in females; degenerative nephritis in kidneys of males and females Study authors' conclusion: NOEL (90d-oral) = 100 mg/kg bw/day for male and female rats. Ref.: 44 90-day oral toxicity in rat (2) (1985-1988) Ten F344/N rats per sex and group received Benzophenone-3 in concentrations of 0; 3,125; 6,250; 12,500; 25,000 and 50,000 ppm in the diet for 13 weeks. The dietary test substance preparations were analyzed for stability and proved to be stable in the diet for at least 3 weeks. Clinical examinations covering clinical signs, mortality, body weight and food consumption were performed in all animals at regula","endpoint":"","ingredient":"INCI name","loael_value":"","noael_unit":"mg/kg bw/day","noael_value":"= 100","page":15,"route":"oral","species":"rat","study_id":"sccp_o_078_noael_005"}
UnifiedCodex:SCCS_SHADOW:beta.noael_studies	-	393	mg/kg bw/day	rat	oral	90d	-	SOURCE_SUBDIR=sccp_o_078; REPORT_TITLE=OPINION ON BENZOPHENONE-3 COLIPA N° S38; OPINION_NUMBER=SCCP/1069/06; COMMITTEE=SCCP; REPORT_DATE=19 December 2006; VALUE_TEXT=393; DOSE=NOAEL (90d-oral) = 429/393 mg/kg bw/day for the male/female rat.; EFFECT=SCCP/1069/06 OPINION ON BENZOPHENONE-3 16 Study authors' conclusion: NOAEL (90d-oral) = 429/393 mg/kg bw/day for the male/female rat. Ref.: 30; CITATION=Ref.: 30; CITATION_NUMBERS=[30]; REFERENCE=Ref.: 30; DETAILS_JSON={"cas_number":"131-57-7","citation":"Ref.: 30","dose":"NOAEL (90d-oral) = 429/393 mg/kg bw/day for the male/female rat.","duration":"90d","effect":"SCCP/1069/06 OPINION ON BENZOPHENONE-3 16 Study authors' conclusion: NOAEL (90d-oral) = 429/393 mg/kg bw/day for the male/female rat. Ref.: 30","endpoint":"","ingredient":"INCI name","loael_value":"","noael_unit":"mg/kg bw/day","noael_value":"393","page":16,"route":"oral","species":"rat","study_id":"sccp_o_078_noael_006"}
UnifiedCodex:SCCS_SHADOW:beta.noael_studies	-	=200	mg/kg bw/day	rat	dermal	90d	-	SOURCE_SUBDIR=sccp_o_078; REPORT_TITLE=OPINION ON BENZOPHENONE-3 COLIPA N° S38; OPINION_NUMBER=SCCP/1069/06; COMMITTEE=SCCP; REPORT_DATE=19 December 2006; VALUE_TEXT== 200; DOSE=SCCP/1069/06 OPINION ON BENZOPHENONE-3 18 200 mg/kg bw/day: non-dosage related increase in relative kidney weight in females; decreased reticulocyte count; increased platelet count; increased whole blood cell count produced by lymphocytosis Study authors' conclusion:; EFFECT=SCCP/1069/06 OPINION ON BENZOPHENONE-3 18 200 mg/kg bw/day: non-dosage related increase in relative kidney weight in females; decreased reticulocyte count; increased platelet count; increased whole blood cell count produced by lymphocytosis Study authors' conclusion: NOAEL (90d-dermal) = 200 mg/kg bw/day for male and female rats. Ref.: 30 90-day dermal toxicity in mouse Ten B6C3F1 mice per sex and group received Benzophenone-3 preparations at dosage levels of 0, 22.8, 45.5, 91, 182, 364 mg/kg bw/day in acetone for 5 days per week over a period of 13 weeks. A constant volume of 0.1 ml was applied over a fixed standard area (10%) of the interscapular region. The area was clipped 24 hours prior to initial application and weekly thereafter. The preparations in acetone were analyzed fo; CITATION=Ref.: 30 90-day dermal toxicity in mouse Ten B6C3F1 mice per sex and group received Benzophenone-3 preparations at dosage levels of 0, 22; CITATION_NUMBERS=[30,90,6,3,1,22]; REFERENCE=Ref.: 30 90-day dermal toxicity in mouse Ten B6C3F1 mice per sex and group received Benzophenone-3 preparations at dosage levels of 0, 22; DETAILS_JSON={"cas_number":"131-57-7","citation":"Ref.: 30 90-day dermal toxicity in mouse Ten B6C3F1 mice per sex and group received Benzophenone-3 preparations at dosage levels of 0, 22","dose":"SCCP/1069/06 OPINION ON BENZOPHENONE-3 18 200 mg/kg bw/day: non-dosage related increase in relative kidney weight in females; decreased reticulocyte count; increased platelet count; increased whole blood cell count produced by lymphocytosis Study authors' conclusion:","duration":"90d","effect":"SCCP/1069/06 OPINION ON BENZOPHENONE-3 18 200 mg/kg bw/day: non-dosage related increase in relative kidney weight in females; decreased reticulocyte count; increased platelet count; increased whole blood cell count produced by lymphocytosis Study authors' conclusion: NOAEL (90d-dermal) = 200 mg/kg bw/day for male and female rats. Ref.: 30 90-day dermal toxicity in mouse Ten B6C3F1 mice per sex and group received Benzophenone-3 preparations at dosage levels of 0, 22.8, 45.5, 91, 182, 364 mg/kg bw/day in acetone for 5 days per week over a period of 13 weeks. A constant volume of 0.1 ml was applied over a fixed standard area (10%) of the interscapular region. The area was clipped 24 hours prior to initial application and weekly thereafter. The preparations in acetone were analyzed fo","endpoint":"","ingredient":"INCI name","loael_value":"","noael_unit":"mg/kg bw/day","noael_value":"= 200","page":18,"route":"dermal","species":"rat","study_id":"sccp_o_078_noael_008"}
UnifiedCodex:SCCS_SHADOW:beta.noael_studies	-	311	mg/kg bw/day	-	oral	14d	-	SOURCE_SUBDIR=sccp_o_078; REPORT_TITLE=OPINION ON BENZOPHENONE-3 COLIPA N° S38; OPINION_NUMBER=SCCP/1069/06; COMMITTEE=SCCP; REPORT_DATE=19 December 2006; VALUE_TEXT=311; DOSE=NOAEL (14d-oral) = 295/311 mg/kg bw/day for the male/female; EFFECT=Unlabeled table on page 12: Study authors' conclusion: NOAEL (14d-oral) = 295/311 mg/kg bw/day for the male/female; CITATION_NUMBERS=[]; DETAILS_JSON={"cas_number":"131-57-7","citation":"","dose":"NOAEL (14d-oral) = 295/311 mg/kg bw/day for the male/female","duration":"14d","effect":"Unlabeled table on page 12: Study authors' conclusion: NOAEL (14d-oral) = 295/311 mg/kg bw/day for the male/female","endpoint":"","ingredient":"INCI name","loael_value":"","noael_unit":"mg/kg bw/day","noael_value":"311","page":12,"route":"oral","species":"","study_id":"sccp_o_078_noael_027"}
UnifiedCodex:SCCS_SHADOW:beta.noael_studies	-	1050	mg/kg bw/day	-	oral	14d	-	SOURCE_SUBDIR=sccp_o_078; REPORT_TITLE=OPINION ON BENZOPHENONE-3 COLIPA N° S38; OPINION_NUMBER=SCCP/1069/06; COMMITTEE=SCCP; REPORT_DATE=19 December 2006; VALUE_TEXT=1050; DOSE=NOAEL (14d-oral) = 992/1050 mg/kg bw/day for the; EFFECT=Unlabeled table on page 13: Study authors' conclusion: NOAEL (14d-oral) = 992/1050 mg/kg bw/day for the; CITATION_NUMBERS=[]; DETAILS_JSON={"cas_number":"131-57-7","citation":"","dose":"NOAEL (14d-oral) = 992/1050 mg/kg bw/day for the","duration":"14d","effect":"Unlabeled table on page 13: Study authors' conclusion: NOAEL (14d-oral) = 992/1050 mg/kg bw/day for the","endpoint":"","ingredient":"INCI name","loael_value":"","noael_unit":"mg/kg bw/day","noael_value":"1050","page":13,"route":"oral","species":"","study_id":"sccp_o_078_noael_028"}
UnifiedCodex:SCCS_SHADOW:beta.noael_studies	-	140	mg/kg bw/day	-	dermal	14d	-	SOURCE_SUBDIR=sccp_o_078; REPORT_TITLE=OPINION ON BENZOPHENONE-3 COLIPA N° S38; OPINION_NUMBER=SCCP/1069/06; COMMITTEE=SCCP; REPORT_DATE=19 December 2006; VALUE_TEXT=140; DOSE=NOAEL (14d-dermal) = 100/140 mg/kg bw/day for the; EFFECT=Unlabeled table on page 13: Study authors' conclusion: NOAEL (14d-dermal) = 100/140 mg/kg bw/day for the; CITATION_NUMBERS=[]; DETAILS_JSON={"cas_number":"131-57-7","citation":"","dose":"NOAEL (14d-dermal) = 100/140 mg/kg bw/day for the","duration":"14d","effect":"Unlabeled table on page 13: Study authors' conclusion: NOAEL (14d-dermal) = 100/140 mg/kg bw/day for the","endpoint":"","ingredient":"INCI name","loael_value":"","noael_unit":"mg/kg bw/day","noael_value":"140","page":13,"route":"dermal","species":"","study_id":"sccp_o_078_noael_029"}
UnifiedCodex:SCCS_SHADOW:beta.noael_studies	-	432	mg/kg bw/day	-	dermal	14d	-	SOURCE_SUBDIR=sccp_o_078; REPORT_TITLE=OPINION ON BENZOPHENONE-3 COLIPA N° S38; OPINION_NUMBER=SCCP/1069/06; COMMITTEE=SCCP; REPORT_DATE=19 December 2006; VALUE_TEXT=432; DOSE=NOAEL (14d-dermal) = 384/432 mg/kg bw/day for the; EFFECT=Unlabeled table on page 14: Study authors' conclusion: NOAEL (14d-dermal) = 384/432 mg/kg bw/day for the; CITATION_NUMBERS=[]; DETAILS_JSON={"cas_number":"131-57-7","citation":"","dose":"NOAEL (14d-dermal) = 384/432 mg/kg bw/day for the","duration":"14d","effect":"Unlabeled table on page 14: Study authors' conclusion: NOAEL (14d-dermal) = 384/432 mg/kg bw/day for the","endpoint":"","ingredient":"INCI name","loael_value":"","noael_unit":"mg/kg bw/day","noael_value":"432","page":14,"route":"dermal","species":"","study_id":"sccp_o_078_noael_030"}
UnifiedCodex:SCCS_SHADOW:beta.noael_studies	-	=100	mg/kg bw/day	rat	oral	90d	-	SOURCE_SUBDIR=sccp_o_078; REPORT_TITLE=OPINION ON BENZOPHENONE-3 COLIPA N° S38; OPINION_NUMBER=SCCP/1069/06; COMMITTEE=SCCP; REPORT_DATE=19 December 2006; VALUE_TEXT== 100; DOSE=NOEL (90d-oral) = 100 mg/kg bw/day for male and female rats.; EFFECT=Unlabeled table on page 15: Study authors' conclusion: NOEL (90d-oral) = 100 mg/kg bw/day for male and female rats.; CITATION_NUMBERS=[]; DETAILS_JSON={"cas_number":"131-57-7","citation":"","dose":"NOEL (90d-oral) = 100 mg/kg bw/day for male and female rats.","duration":"90d","effect":"Unlabeled table on page 15: Study authors' conclusion: NOEL (90d-oral) = 100 mg/kg bw/day for male and female rats.","endpoint":"","ingredient":"INCI name","loael_value":"","noael_unit":"mg/kg bw/day","noael_value":"= 100","page":15,"route":"oral","species":"rat","study_id":"sccp_o_078_noael_031"}
UnifiedCodex:SCCS_SHADOW:beta.noael_studies	-	393	mg/kg bw/day	-	oral	90d	-	SOURCE_SUBDIR=sccp_o_078; REPORT_TITLE=OPINION ON BENZOPHENONE-3 COLIPA N° S38; OPINION_NUMBER=SCCP/1069/06; COMMITTEE=SCCP; REPORT_DATE=19 December 2006; VALUE_TEXT=393; DOSE=NOAEL (90d-oral) = 429/393 mg/kg bw/day for the male/female; EFFECT=Unlabeled table on page 16: Study authors' conclusion: NOAEL (90d-oral) = 429/393 mg/kg bw/day for the male/female; CITATION_NUMBERS=[]; DETAILS_JSON={"cas_number":"131-57-7","citation":"","dose":"NOAEL (90d-oral) = 429/393 mg/kg bw/day for the male/female","duration":"90d","effect":"Unlabeled table on page 16: Study authors' conclusion: NOAEL (90d-oral) = 429/393 mg/kg bw/day for the male/female","endpoint":"","ingredient":"INCI name","loael_value":"","noael_unit":"mg/kg bw/day","noael_value":"393","page":16,"route":"oral","species":"","study_id":"sccp_o_078_noael_032"}
UnifiedCodex:SCCS_SHADOW:beta.noael_studies	-	1425	mg/kg bw/day	-	oral	90d	-	SOURCE_SUBDIR=sccp_o_078; REPORT_TITLE=OPINION ON BENZOPHENONE-3 COLIPA N° S38; OPINION_NUMBER=SCCP/1069/06; COMMITTEE=SCCP; REPORT_DATE=19 December 2006; VALUE_TEXT=1425; DOSE=NOAEL (90d-oral) = 1068/1425 mg/kg bw/day for the; EFFECT=Unlabeled table on page 17: Study authors' conclusion: NOAEL (90d-oral) = 1068/1425 mg/kg bw/day for the; CITATION_NUMBERS=[]; DETAILS_JSON={"cas_number":"131-57-7","citation":"","dose":"NOAEL (90d-oral) = 1068/1425 mg/kg bw/day for the","duration":"90d","effect":"Unlabeled table on page 17: Study authors' conclusion: NOAEL (90d-oral) = 1068/1425 mg/kg bw/day for the","endpoint":"","ingredient":"INCI name","loael_value":"","noael_unit":"mg/kg bw/day","noael_value":"1425","page":17,"route":"oral","species":"","study_id":"sccp_o_078_noael_033"}
UnifiedCodex:SCCS_SHADOW:beta.noael_studies	-	=200	mg/kg bw/day	-	dermal	90d	-	SOURCE_SUBDIR=sccp_o_078; REPORT_TITLE=OPINION ON BENZOPHENONE-3 COLIPA N° S38; OPINION_NUMBER=SCCP/1069/06; COMMITTEE=SCCP; REPORT_DATE=19 December 2006; VALUE_TEXT== 200; DOSE=NOAEL (90d-dermal) = 200 mg/kg bw/day for male and female; EFFECT=Unlabeled table on page 18: Study authors' conclusion: NOAEL (90d-dermal) = 200 mg/kg bw/day for male and female; CITATION_NUMBERS=[]; DETAILS_JSON={"cas_number":"131-57-7","citation":"","dose":"NOAEL (90d-dermal) = 200 mg/kg bw/day for male and female","duration":"90d","effect":"Unlabeled table on page 18: Study authors' conclusion: NOAEL (90d-dermal) = 200 mg/kg bw/day for male and female","endpoint":"","ingredient":"INCI name","loael_value":"","noael_unit":"mg/kg bw/day","noael_value":"= 200","page":18,"route":"dermal","species":"","study_id":"sccp_o_078_noael_034"}
UnifiedCodex:SCCS_SHADOW:beta.noael_studies	-	=364	mg/kg bw/day	-	dermal	90d	-	SOURCE_SUBDIR=sccp_o_078; REPORT_TITLE=OPINION ON BENZOPHENONE-3 COLIPA N° S38; OPINION_NUMBER=SCCP/1069/06; COMMITTEE=SCCP; REPORT_DATE=19 December 2006; VALUE_TEXT== 364; DOSE=NOAEL (90d-dermal) = 364 mg/kg bw/day for male and female; EFFECT=Unlabeled table on page 18: Study authors' conclusion: NOAEL (90d-dermal) = 364 mg/kg bw/day for male and female; CITATION_NUMBERS=[]; DETAILS_JSON={"cas_number":"131-57-7","citation":"","dose":"NOAEL (90d-dermal) = 364 mg/kg bw/day for male and female","duration":"90d","effect":"Unlabeled table on page 18: Study authors' conclusion: NOAEL (90d-dermal) = 364 mg/kg bw/day for male and female","endpoint":"","ingredient":"INCI name","loael_value":"","noael_unit":"mg/kg bw/day","noael_value":"= 364","page":18,"route":"dermal","species":"","study_id":"sccp_o_078_noael_035"}
UnifiedCodex:SCCS_SHADOW:beta.noael_studies	-	200	mg/kg bw/day	rat	-	-	-	SOURCE_SUBDIR=sccp_o_078; REPORT_TITLE=OPINION ON BENZOPHENONE-3 COLIPA N° S38; OPINION_NUMBER=SCCP/1069/06; COMMITTEE=SCCP; REPORT_DATE=19 December 2006; VALUE_TEXT=200; DOSE=Adverse-Effect-Level (NOAEL), namely 200 mg/kg bw/day in rats and 364 mg/kg bw/day in; EFFECT=Unlabeled table on page 19: Adverse-Effect-Level (NOAEL), namely 200 mg/kg bw/day in rats and 364 mg/kg bw/day in; CITATION_NUMBERS=[]; DETAILS_JSON={"cas_number":"131-57-7","citation":"","dose":"Adverse-Effect-Level (NOAEL), namely 200 mg/kg bw/day in rats and 364 mg/kg bw/day in","duration":"","effect":"Unlabeled table on page 19: Adverse-Effect-Level (NOAEL), namely 200 mg/kg bw/day in rats and 364 mg/kg bw/day in","endpoint":"","ingredient":"INCI name","loael_value":"","noael_unit":"mg/kg bw/day","noael_value":"200","page":19,"route":"","species":"rat","study_id":"sccp_o_078_noael_037"}
UnifiedCodex:SCCS_SHADOW:beta.noael_studies	-	1980	-	-	-	-	-	SOURCE_SUBDIR=sccp_o_078; REPORT_TITLE=OPINION ON BENZOPHENONE-3 COLIPA N° S38; OPINION_NUMBER=SCCP/1069/06; COMMITTEE=SCCP; REPORT_DATE=19 December 2006; VALUE_TEXT=A number of publications (1980-1992) describe the results of Benzophenone-3 studied in; EFFECT=Unlabeled table on page 19: A number of publications (1980-1992) describe the results of Benzophenone-3 studied in; CITATION_NUMBERS=[]; DETAILS_JSON={"cas_number":"131-57-7","citation":"","dose":"","duration":"","effect":"Unlabeled table on page 19: A number of publications (1980-1992) describe the results of Benzophenone-3 studied in","endpoint":"","ingredient":"INCI name","loael_value":"","noael_unit":"","noael_value":"A number of publications (1980-1992) describe the results of Benzophenone-3 studied in","page":19,"route":"","species":"","study_id":"sccp_o_078_noael_038"}
UnifiedCodex:SCCS_SHADOW:beta.noael_studies	-	36	-	-	-	-	-	SOURCE_SUBDIR=sccp_o_078; REPORT_TITLE=OPINION ON BENZOPHENONE-3 COLIPA N° S38; OPINION_NUMBER=SCCP/1069/06; COMMITTEE=SCCP; REPORT_DATE=19 December 2006; VALUE_TEXT=and a title page [36] to a more extensive description of the materials and methods [73].; EFFECT=Unlabeled table on page 19: and a title page [36] to a more extensive description of the materials and methods [73].; CITATION_NUMBERS=[]; DETAILS_JSON={"cas_number":"131-57-7","citation":"","dose":"","duration":"","effect":"Unlabeled table on page 19: and a title page [36] to a more extensive description of the materials and methods [73].","endpoint":"","ingredient":"INCI name","loael_value":"","noael_unit":"","noael_value":"and a title page [36] to a more extensive description of the materials and methods [73].","page":19,"route":"","species":"","study_id":"sccp_o_078_noael_039"}
UnifiedCodex:SCCS_SHADOW:beta.noael_studies	-	9	-	-	-	-	-	SOURCE_SUBDIR=sccp_o_078; REPORT_TITLE=OPINION ON BENZOPHENONE-3 COLIPA N° S38; OPINION_NUMBER=SCCP/1069/06; COMMITTEE=SCCP; REPORT_DATE=19 December 2006; VALUE_TEXT=bacteria both, with and without metabolic activation (S9 mix from the liver of Aroclor 1254-; EFFECT=Unlabeled table on page 19: bacteria both, with and without metabolic activation (S9 mix from the liver of Aroclor 1254-; CITATION_NUMBERS=[]; DETAILS_JSON={"cas_number":"131-57-7","citation":"","dose":"","duration":"","effect":"Unlabeled table on page 19: bacteria both, with and without metabolic activation (S9 mix from the liver of Aroclor 1254-","endpoint":"","ingredient":"INCI name","loael_value":"","noael_unit":"","noael_value":"bacteria both, with and without metabolic activation (S9 mix from the liver of Aroclor 1254-","page":19,"route":"","species":"","study_id":"sccp_o_078_noael_040"}
UnifiedCodex:SCCS_SHADOW:beta.noael_studies	-	10	%	-	-	-	-	SOURCE_SUBDIR=sccp_o_078; REPORT_TITLE=OPINION ON BENZOPHENONE-3 COLIPA N° S38; OPINION_NUMBER=SCCP/1069/06; COMMITTEE=SCCP; REPORT_DATE=19 December 2006; VALUE_TEXT=10; EFFECT=Unlabeled table on page 19: prepared immediately prior to use and contained 10% S9. The tested Salmonella; CITATION_NUMBERS=[]; DETAILS_JSON={"cas_number":"131-57-7","citation":"","dose":"","duration":"","effect":"Unlabeled table on page 19: prepared immediately prior to use and contained 10% S9. The tested Salmonella","endpoint":"","ingredient":"INCI name","loael_value":"","noael_unit":"%","noael_value":"10","page":19,"route":"","species":"","study_id":"sccp_o_078_noael_041"}
UnifiedCodex:SCCS_SHADOW:beta.noael_studies	-	97	-	-	-	-	-	SOURCE_SUBDIR=sccp_o_078; REPORT_TITLE=OPINION ON BENZOPHENONE-3 COLIPA N° S38; OPINION_NUMBER=SCCP/1069/06; COMMITTEE=SCCP; REPORT_DATE=19 December 2006; VALUE_TEXT=typhimurium strains were combinations of TA97, TA98, TA100, TA1535, TA1537 and/or; EFFECT=Unlabeled table on page 19: typhimurium strains were combinations of TA97, TA98, TA100, TA1535, TA1537 and/or; CITATION_NUMBERS=[]; DETAILS_JSON={"cas_number":"131-57-7","citation":"","dose":"","duration":"","effect":"Unlabeled table on page 19: typhimurium strains were combinations of TA97, TA98, TA100, TA1535, TA1537 and/or","endpoint":"","ingredient":"INCI name","loael_value":"","noael_unit":"","noael_value":"typhimurium strains were combinations of TA97, TA98, TA100, TA1535, TA1537 and/or","page":19,"route":"","species":"","study_id":"sccp_o_078_noael_042"}
UnifiedCodex:SCCS_SHADOW:beta.noael_studies	-	1538	-	-	-	-	-	SOURCE_SUBDIR=sccp_o_078; REPORT_TITLE=OPINION ON BENZOPHENONE-3 COLIPA N° S38; OPINION_NUMBER=SCCP/1069/06; COMMITTEE=SCCP; REPORT_DATE=19 December 2006; VALUE_TEXT=TA1538 and were exposed to the test substance at various concentrations of; EFFECT=Unlabeled table on page 19: TA1538 and were exposed to the test substance at various concentrations of; CITATION_NUMBERS=[]; DETAILS_JSON={"cas_number":"131-57-7","citation":"","dose":"","duration":"","effect":"Unlabeled table on page 19: TA1538 and were exposed to the test substance at various concentrations of","endpoint":"","ingredient":"INCI name","loael_value":"","noael_unit":"","noael_value":"TA1538 and were exposed to the test substance at various concentrations of","page":19,"route":"","species":"","study_id":"sccp_o_078_noael_043"}
UnifiedCodex:SCCS_SHADOW:beta.noael_studies	-	-3	-	-	-	-	-	SOURCE_SUBDIR=sccp_o_078; REPORT_TITLE=OPINION ON BENZOPHENONE-3 COLIPA N° S38; OPINION_NUMBER=SCCP/1069/06; COMMITTEE=SCCP; REPORT_DATE=19 December 2006; VALUE_TEXT=Benzophenone-3 with and without S9 mix. Positive controls were included to demonstrate; EFFECT=Unlabeled table on page 19: Benzophenone-3 with and without S9 mix. Positive controls were included to demonstrate; CITATION_NUMBERS=[]; DETAILS_JSON={"cas_number":"131-57-7","citation":"","dose":"","duration":"","effect":"Unlabeled table on page 19: Benzophenone-3 with and without S9 mix. Positive controls were included to demonstrate","endpoint":"","ingredient":"INCI name","loael_value":"","noael_unit":"","noael_value":"Benzophenone-3 with and without S9 mix. Positive controls were included to demonstrate","page":19,"route":"","species":"","study_id":"sccp_o_078_noael_044"}
UnifiedCodex:SCCS_SHADOW:beta.noael_studies	-	73	-	-	-	-	-	SOURCE_SUBDIR=sccp_o_078; REPORT_TITLE=OPINION ON BENZOPHENONE-3 COLIPA N° S38; OPINION_NUMBER=SCCP/1069/06; COMMITTEE=SCCP; REPORT_DATE=19 December 2006; VALUE_TEXT=Bacteriotoxicity was reported [73] to be observed at a varying degree at and above 333; EFFECT=Unlabeled table on page 19: Bacteriotoxicity was reported [73] to be observed at a varying degree at and above 333; CITATION_NUMBERS=[]; DETAILS_JSON={"cas_number":"131-57-7","citation":"","dose":"","duration":"","effect":"Unlabeled table on page 19: Bacteriotoxicity was reported [73] to be observed at a varying degree at and above 333","endpoint":"","ingredient":"INCI name","loael_value":"","noael_unit":"","noael_value":"Bacteriotoxicity was reported [73] to be observed at a varying degree at and above 333","page":19,"route":"","species":"","study_id":"sccp_o_078_noael_045"}
UnifiedCodex:SCCS_SHADOW:beta.noael_studies	-	1000	-	-	-	-	-	SOURCE_SUBDIR=sccp_o_078; REPORT_TITLE=OPINION ON BENZOPHENONE-3 COLIPA N° S38; OPINION_NUMBER=SCCP/1069/06; COMMITTEE=SCCP; REPORT_DATE=19 December 2006; VALUE_TEXT=µg/plate and at 1000 µg/plate in all tested strains (TA98, TA100, TA1535, TA1537). In that; EFFECT=Unlabeled table on page 19: µg/plate and at 1000 µg/plate in all tested strains (TA98, TA100, TA1535, TA1537). In that; CITATION_NUMBERS=[]; DETAILS_JSON={"cas_number":"131-57-7","citation":"","dose":"","duration":"","effect":"Unlabeled table on page 19: µg/plate and at 1000 µg/plate in all tested strains (TA98, TA100, TA1535, TA1537). In that","endpoint":"","ingredient":"INCI name","loael_value":"","noael_unit":"","noael_value":"µg/plate and at 1000 µg/plate in all tested strains (TA98, TA100, TA1535, TA1537). In that","page":19,"route":"","species":"","study_id":"sccp_o_078_noael_046"}
UnifiedCodex:SCCS_SHADOW:beta.noael_studies	-	97	-	-	-	-	-	SOURCE_SUBDIR=sccp_o_078; REPORT_TITLE=OPINION ON BENZOPHENONE-3 COLIPA N° S38; OPINION_NUMBER=SCCP/1069/06; COMMITTEE=SCCP; REPORT_DATE=19 December 2006; VALUE_TEXT=same publication, Salmonella Typhimurium TA97 was additionally tested and showed a; EFFECT=Unlabeled table on page 19: same publication, Salmonella Typhimurium TA97 was additionally tested and showed a; CITATION_NUMBERS=[]; DETAILS_JSON={"cas_number":"131-57-7","citation":"","dose":"","duration":"","effect":"Unlabeled table on page 19: same publication, Salmonella Typhimurium TA97 was additionally tested and showed a","endpoint":"","ingredient":"INCI name","loael_value":"","noael_unit":"","noael_value":"same publication, Salmonella Typhimurium TA97 was additionally tested and showed a","page":19,"route":"","species":"","study_id":"sccp_o_078_noael_047"}
UnifiedCodex:SCCS_SHADOW:beta.noael_studies	-	30	%	-	-	-	-	SOURCE_SUBDIR=sccp_o_078; REPORT_TITLE=OPINION ON BENZOPHENONE-3 COLIPA N° S38; OPINION_NUMBER=SCCP/1069/06; COMMITTEE=SCCP; REPORT_DATE=19 December 2006; VALUE_TEXT=30; EFFECT=Unlabeled table on page 19: weak mutagenic response using 30% of S9 hamster mix.; CITATION_NUMBERS=[]; DETAILS_JSON={"cas_number":"131-57-7","citation":"","dose":"","duration":"","effect":"Unlabeled table on page 19: weak mutagenic response using 30% of S9 hamster mix.","endpoint":"","ingredient":"INCI name","loael_value":"","noael_unit":"%","noael_value":"30","page":19,"route":"","species":"","study_id":"sccp_o_078_noael_048"}
UnifiedCodex:SCCS_SHADOW:beta.noael_studies	-	10	%	rat	-	-	-	SOURCE_SUBDIR=sccp_o_078; REPORT_TITLE=OPINION ON BENZOPHENONE-3 COLIPA N° S38; OPINION_NUMBER=SCCP/1069/06; COMMITTEE=SCCP; REPORT_DATE=19 December 2006; VALUE_TEXT=10; EFFECT=Unlabeled table on page 19: However, no effect was noted using 10% hamster or 10% and 30% rat S9 mix compared to; CITATION_NUMBERS=[]; DETAILS_JSON={"cas_number":"131-57-7","citation":"","dose":"","duration":"","effect":"Unlabeled table on page 19: However, no effect was noted using 10% hamster or 10% and 30% rat S9 mix compared to","endpoint":"","ingredient":"INCI name","loael_value":"","noael_unit":"%","noael_value":"10","page":19,"route":"","species":"rat","study_id":"sccp_o_078_noael_049"}
UnifiedCodex:SCCS_SHADOW:beta.noael_studies	-	2	-	-	-	-	-	SOURCE_SUBDIR=sccp_o_078; REPORT_TITLE=OPINION ON BENZOPHENONE-3 COLIPA N° S38; OPINION_NUMBER=SCCP/1069/06; COMMITTEE=SCCP; REPORT_DATE=19 December 2006; VALUE_TEXT=the respective controls, the increase in the numbers of revertants was less than 2-fold; EFFECT=Unlabeled table on page 19: the respective controls, the increase in the numbers of revertants was less than 2-fold; CITATION_NUMBERS=[]; DETAILS_JSON={"cas_number":"131-57-7","citation":"","dose":"","duration":"","effect":"Unlabeled table on page 19: the respective controls, the increase in the numbers of revertants was less than 2-fold","endpoint":"","ingredient":"INCI name","loael_value":"","noael_unit":"","noael_value":"the respective controls, the increase in the numbers of revertants was less than 2-fold","page":19,"route":"","species":"","study_id":"sccp_o_078_noael_050"}
UnifiedCodex:SCCS_SHADOW:beta.noael_studies	-	-3	-	-	-	-	-	SOURCE_SUBDIR=sccp_o_078; REPORT_TITLE=OPINION ON BENZOPHENONE-3 COLIPA N° S38; OPINION_NUMBER=SCCP/1069/06; COMMITTEE=SCCP; REPORT_DATE=19 December 2006; VALUE_TEXT=Benzophenone-3 showed to be negative for the induction of revertants in all other strains at; EFFECT=Unlabeled table on page 19: Benzophenone-3 showed to be negative for the induction of revertants in all other strains at; CITATION_NUMBERS=[]; DETAILS_JSON={"cas_number":"131-57-7","citation":"","dose":"","duration":"","effect":"Unlabeled table on page 19: Benzophenone-3 showed to be negative for the induction of revertants in all other strains at","endpoint":"","ingredient":"INCI name","loael_value":"","noael_unit":"","noael_value":"Benzophenone-3 showed to be negative for the induction of revertants in all other strains at","page":19,"route":"","species":"","study_id":"sccp_o_078_noael_051"}
UnifiedCodex:SCCS_SHADOW:beta.noael_studies	-	3	-	-	-	-	-	SOURCE_SUBDIR=sccp_o_078; REPORT_TITLE=OPINION ON BENZOPHENONE-3 COLIPA N° S38; OPINION_NUMBER=SCCP/1069/06; COMMITTEE=SCCP; REPORT_DATE=19 December 2006; VALUE_TEXT=the tested concentration range between 3 and 333 µg/plate. All other studies (not including; EFFECT=Unlabeled table on page 19: the tested concentration range between 3 and 333 µg/plate. All other studies (not including; CITATION_NUMBERS=[]; DETAILS_JSON={"cas_number":"131-57-7","citation":"","dose":"","duration":"","effect":"Unlabeled table on page 19: the tested concentration range between 3 and 333 µg/plate. All other studies (not including","endpoint":"","ingredient":"INCI name","loael_value":"","noael_unit":"","noael_value":"the tested concentration range between 3 and 333 µg/plate. All other studies (not including","page":19,"route":"","species":"","study_id":"sccp_o_078_noael_052"}
UnifiedCodex:SCCS_SHADOW:beta.noael_studies	-	97	-	-	-	-	-	SOURCE_SUBDIR=sccp_o_078; REPORT_TITLE=OPINION ON BENZOPHENONE-3 COLIPA N° S38; OPINION_NUMBER=SCCP/1069/06; COMMITTEE=SCCP; REPORT_DATE=19 December 2006; VALUE_TEXT=TA97 in their testing battery) showed Benzophenone-3 to be negative in the Ames test.; EFFECT=Unlabeled table on page 19: TA97 in their testing battery) showed Benzophenone-3 to be negative in the Ames test.; CITATION_NUMBERS=[]; DETAILS_JSON={"cas_number":"131-57-7","citation":"","dose":"","duration":"","effect":"Unlabeled table on page 19: TA97 in their testing battery) showed Benzophenone-3 to be negative in the Ames test.","endpoint":"","ingredient":"INCI name","loael_value":"","noael_unit":"","noael_value":"TA97 in their testing battery) showed Benzophenone-3 to be negative in the Ames test.","page":19,"route":"","species":"","study_id":"sccp_o_078_noael_053"}
UnifiedCodex:SCCS_SHADOW:beta.noael_studies	-	-3	-	-	-	-	-	SOURCE_SUBDIR=sccp_o_078; REPORT_TITLE=OPINION ON BENZOPHENONE-3 COLIPA N° S38; OPINION_NUMBER=SCCP/1069/06; COMMITTEE=SCCP; REPORT_DATE=19 December 2006; VALUE_TEXT=Considering the fact that Benzophenone-3 did not induce gene mutations by base pair; EFFECT=Unlabeled table on page 19: Considering the fact that Benzophenone-3 did not induce gene mutations by base pair; CITATION_NUMBERS=[]; DETAILS_JSON={"cas_number":"131-57-7","citation":"","dose":"","duration":"","effect":"Unlabeled table on page 19: Considering the fact that Benzophenone-3 did not induce gene mutations by base pair","endpoint":"","ingredient":"INCI name","loael_value":"","noael_unit":"","noael_value":"Considering the fact that Benzophenone-3 did not induce gene mutations by base pair","page":19,"route":"","species":"","study_id":"sccp_o_078_noael_054"}
UnifiedCodex:SCCS_SHADOW:beta.noael_studies	-	9	-	-	-	-	-	SOURCE_SUBDIR=sccp_o_078; REPORT_TITLE=OPINION ON BENZOPHENONE-3 COLIPA N° S38; OPINION_NUMBER=SCCP/1069/06; COMMITTEE=SCCP; REPORT_DATE=19 December 2006; VALUE_TEXT=presence and absence of S9-mix, the compound is considered to be non-mutagenic in the; EFFECT=Unlabeled table on page 19: presence and absence of S9-mix, the compound is considered to be non-mutagenic in the; CITATION_NUMBERS=[]; DETAILS_JSON={"cas_number":"131-57-7","citation":"","dose":"","duration":"","effect":"Unlabeled table on page 19: presence and absence of S9-mix, the compound is considered to be non-mutagenic in the","endpoint":"","ingredient":"INCI name","loael_value":"","noael_unit":"","noael_value":"presence and absence of S9-mix, the compound is considered to be non-mutagenic in the","page":19,"route":"","species":"","study_id":"sccp_o_078_noael_055"}
UnifiedCodex:SCCS_SHADOW:beta.noael_studies	-	9	-	-	-	-	-	SOURCE_SUBDIR=sccp_o_078; REPORT_TITLE=OPINION ON BENZOPHENONE-3 COLIPA N° S38; OPINION_NUMBER=SCCP/1069/06; COMMITTEE=SCCP; REPORT_DATE=19 December 2006; VALUE_TEXT=one specific S9 mix, is considered irrelevant by the authors of the submission.; EFFECT=Unlabeled table on page 19: one specific S9 mix, is considered irrelevant by the authors of the submission.; CITATION_NUMBERS=[]; DETAILS_JSON={"cas_number":"131-57-7","citation":"","dose":"","duration":"","effect":"Unlabeled table on page 19: one specific S9 mix, is considered irrelevant by the authors of the submission.","endpoint":"","ingredient":"INCI name","loael_value":"","noael_unit":"","noael_value":"one specific S9 mix, is considered irrelevant by the authors of the submission.","page":19,"route":"","species":"","study_id":"sccp_o_078_noael_056"}
UnifiedCodex:SCCS_SHADOW:beta.noael_studies	-	8	-	-	-	-	-	SOURCE_SUBDIR=sccp_o_078; REPORT_TITLE=OPINION ON BENZOPHENONE-3 COLIPA N° S38; OPINION_NUMBER=SCCP/1069/06; COMMITTEE=SCCP; REPORT_DATE=19 December 2006; VALUE_TEXT=Ref.: 8, 30, 36, 73; EFFECT=Unlabeled table on page 19: Ref.: 8, 30, 36, 73; CITATION=Ref.: 8, 30, 36, 73; CITATION_NUMBERS=[8,30,36,73]; REFERENCE=Ref.: 8, 30, 36, 73; DETAILS_JSON={"cas_number":"131-57-7","citation":"Ref.: 8, 30, 36, 73","dose":"","duration":"","effect":"Unlabeled table on page 19: Ref.: 8, 30, 36, 73","endpoint":"","ingredient":"INCI name","loael_value":"","noael_unit":"","noael_value":"Ref.: 8, 30, 36, 73","page":19,"route":"","species":"","study_id":"sccp_o_078_noael_057"}
UnifiedCodex:SCCS_SHADOW:beta.noael_studies	-	1992	-	-	-	-	-	SOURCE_SUBDIR=sccp_o_078; REPORT_TITLE=OPINION ON BENZOPHENONE-3 COLIPA N° S38; OPINION_NUMBER=SCCP/1069/06; COMMITTEE=SCCP; REPORT_DATE=19 December 2006; VALUE_TEXT=A US National Toxicology program report (1992) briefly describes the results of cytogenetic; EFFECT=Unlabeled table on page 19: A US National Toxicology program report (1992) briefly describes the results of cytogenetic; CITATION_NUMBERS=[]; DETAILS_JSON={"cas_number":"131-57-7","citation":"","dose":"","duration":"","effect":"Unlabeled table on page 19: A US National Toxicology program report (1992) briefly describes the results of cytogenetic","endpoint":"","ingredient":"INCI name","loael_value":"","noael_unit":"","noael_value":"A US National Toxicology program report (1992) briefly describes the results of cytogenetic","page":19,"route":"","species":"","study_id":"sccp_o_078_noael_058"}
UnifiedCodex:SCCS_SHADOW:beta.noael_studies	-	-3	-	-	-	-	-	SOURCE_SUBDIR=sccp_o_078; REPORT_TITLE=OPINION ON BENZOPHENONE-3 COLIPA N° S38; OPINION_NUMBER=SCCP/1069/06; COMMITTEE=SCCP; REPORT_DATE=19 December 2006; VALUE_TEXT=tests with Chinese hamster ovary cells, in which Benzophenone-3-induced sister-chromatid; EFFECT=Unlabeled table on page 19: tests with Chinese hamster ovary cells, in which Benzophenone-3-induced sister-chromatid; CITATION_NUMBERS=[]; DETAILS_JSON={"cas_number":"131-57-7","citation":"","dose":"","duration":"","effect":"Unlabeled table on page 19: tests with Chinese hamster ovary cells, in which Benzophenone-3-induced sister-chromatid","endpoint":"","ingredient":"INCI name","loael_value":"","noael_unit":"","noael_value":"tests with Chinese hamster ovary cells, in which Benzophenone-3-induced sister-chromatid","page":19,"route":"","species":"","study_id":"sccp_o_078_noael_059"}
UnifiedCodex:SCCS_SHADOW:beta.noael_studies	-	5	-	-	-	-	-	SOURCE_SUBDIR=sccp_o_078; REPORT_TITLE=OPINION ON BENZOPHENONE-3 COLIPA N° S38; OPINION_NUMBER=SCCP/1069/06; COMMITTEE=SCCP; REPORT_DATE=19 December 2006; VALUE_TEXT=exchanges (effective dose range 5-50µg/ml) and chromosomal aberrations (20-45µg/ml) in; DOSE=Unlabeled table on page 19: exchanges (effective dose range 5-50µg/ml) and chromosomal aberrations (20-45µg/ml) in; EFFECT=Unlabeled table on page 19: exchanges (effective dose range 5-50µg/ml) and chromosomal aberrations (20-45µg/ml) in; CITATION_NUMBERS=[]; DETAILS_JSON={"cas_number":"131-57-7","citation":"","dose":"Unlabeled table on page 19: exchanges (effective dose range 5-50µg/ml) and chromosomal aberrations (20-45µg/ml) in","duration":"","effect":"Unlabeled table on page 19: exchanges (effective dose range 5-50µg/ml) and chromosomal aberrations (20-45µg/ml) in","endpoint":"","ingredient":"INCI name","loael_value":"","noael_unit":"","noael_value":"exchanges (effective dose range 5-50µg/ml) and chromosomal aberrations (20-45µg/ml) in","page":19,"route":"","species":"","study_id":"sccp_o_078_noael_060"}
UnifiedCodex:SCCS_SHADOW:beta.noael_studies	-	1254	-	rat	-	-	-	SOURCE_SUBDIR=sccp_o_078; REPORT_TITLE=OPINION ON BENZOPHENONE-3 COLIPA N° S38; OPINION_NUMBER=SCCP/1069/06; COMMITTEE=SCCP; REPORT_DATE=19 December 2006; VALUE_TEXT=the presence of Aroclor 1254-induced male Sprague Dawley rat liver S9.; EFFECT=Unlabeled table on page 19: the presence of Aroclor 1254-induced male Sprague Dawley rat liver S9.; CITATION_NUMBERS=[]; DETAILS_JSON={"cas_number":"131-57-7","citation":"","dose":"","duration":"","effect":"Unlabeled table on page 19: the presence of Aroclor 1254-induced male Sprague Dawley rat liver S9.","endpoint":"","ingredient":"INCI name","loael_value":"","noael_unit":"","noael_value":"the presence of Aroclor 1254-induced male Sprague Dawley rat liver S9.","page":19,"route":"","species":"rat","study_id":"sccp_o_078_noael_061"}
UnifiedCodex:SCCS_SHADOW:beta.noael_studies	-	=828	mg/kg bw/day	-	-	-	-	SOURCE_SUBDIR=sccp_o_078; REPORT_TITLE=OPINION ON BENZOPHENONE-3 COLIPA N° S38; OPINION_NUMBER=SCCP/1069/06; COMMITTEE=SCCP; REPORT_DATE=19 December 2006; VALUE_TEXT== 828; DOSE=NOAEL (reproduction) = 828 mg/kg bw/day for male and female; EFFECT=Unlabeled table on page 21: Study authors' conclusion: NOAEL (reproduction) = 828 mg/kg bw/day for male and female; CITATION_NUMBERS=[]; DETAILS_JSON={"cas_number":"131-57-7","citation":"","dose":"NOAEL (reproduction) = 828 mg/kg bw/day for male and female","duration":"","effect":"Unlabeled table on page 21: Study authors' conclusion: NOAEL (reproduction) = 828 mg/kg bw/day for male and female","endpoint":"","ingredient":"INCI name","loael_value":"","noael_unit":"mg/kg bw/day","noael_value":"= 828","page":21,"route":"","species":"","study_id":"sccp_o_078_noael_062"}
UnifiedCodex:SCCS_SHADOW:beta.noael_studies	-	=2860	mg/kg bw/day	-	-	-	-	SOURCE_SUBDIR=sccp_o_078; REPORT_TITLE=OPINION ON BENZOPHENONE-3 COLIPA N° S38; OPINION_NUMBER=SCCP/1069/06; COMMITTEE=SCCP; REPORT_DATE=19 December 2006; VALUE_TEXT== 2,860; DOSE=NOAEL (reproduction) = 2,860 mg/kg bw/day for male and; EFFECT=Unlabeled table on page 22: Study authors' conclusion: NOAEL (reproduction) = 2,860 mg/kg bw/day for male and; CITATION_NUMBERS=[]; DETAILS_JSON={"cas_number":"131-57-7","citation":"","dose":"NOAEL (reproduction) = 2,860 mg/kg bw/day for male and","duration":"","effect":"Unlabeled table on page 22: Study authors' conclusion: NOAEL (reproduction) = 2,860 mg/kg bw/day for male and","endpoint":"","ingredient":"INCI name","loael_value":"","noael_unit":"mg/kg bw/day","noael_value":"= 2,860","page":22,"route":"","species":"","study_id":"sccp_o_078_noael_063"}
UnifiedCodex:SCCS_SHADOW:beta.noael_studies	-	=400	mg/kg bw/day	-	-	-	-	SOURCE_SUBDIR=sccp_o_078; REPORT_TITLE=OPINION ON BENZOPHENONE-3 COLIPA N° S38; OPINION_NUMBER=SCCP/1069/06; COMMITTEE=SCCP; REPORT_DATE=19 December 2006; VALUE_TEXT== 400; DOSE=NOAEL (reproduction) = 400 mg/kg bw/day for male and female; EFFECT=Unlabeled table on page 23: Study authors' conclusion: NOAEL (reproduction) = 400 mg/kg bw/day for male and female; CITATION_NUMBERS=[]; DETAILS_JSON={"cas_number":"131-57-7","citation":"","dose":"NOAEL (reproduction) = 400 mg/kg bw/day for male and female","duration":"","effect":"Unlabeled table on page 23: Study authors' conclusion: NOAEL (reproduction) = 400 mg/kg bw/day for male and female","endpoint":"","ingredient":"INCI name","loael_value":"","noael_unit":"mg/kg bw/day","noael_value":"= 400","page":23,"route":"","species":"","study_id":"sccp_o_078_noael_065"}
UnifiedCodex:SCCS_SHADOW:beta.noael_studies	-	200	mg/kg bw/day	rat	-	-	-	SOURCE_SUBDIR=sccp_o_078; REPORT_TITLE=OPINION ON BENZOPHENONE-3 COLIPA N° S38; OPINION_NUMBER=SCCP/1069/06; COMMITTEE=SCCP; REPORT_DATE=19 December 2006; VALUE_TEXT=200; DOSE=Unlabeled table on page 24: specifically 200 mg/kg bw/day for the rat and 364 mg/kg bw/day for the mouse.; EFFECT=Unlabeled table on page 24: specifically 200 mg/kg bw/day for the rat and 364 mg/kg bw/day for the mouse.; CITATION_NUMBERS=[]; DETAILS_JSON={"cas_number":"131-57-7","citation":"","dose":"Unlabeled table on page 24: specifically 200 mg/kg bw/day for the rat and 364 mg/kg bw/day for the mouse.","duration":"","effect":"Unlabeled table on page 24: specifically 200 mg/kg bw/day for the rat and 364 mg/kg bw/day for the mouse.","endpoint":"","ingredient":"INCI name","loael_value":"","noael_unit":"mg/kg bw/day","noael_value":"200","page":24,"route":"","species":"rat","study_id":"sccp_o_078_noael_068"}
UnifiedCodex:SCCS_SHADOW:beta.noael_studies	-	1	-	-	-	-	-	SOURCE_SUBDIR=sccp_o_078; REPORT_TITLE=OPINION ON BENZOPHENONE-3 COLIPA N° S38; OPINION_NUMBER=SCCP/1069/06; COMMITTEE=SCCP; REPORT_DATE=19 December 2006; VALUE_TEXT=Date of study: 01-16 November 2004; EFFECT=Unlabeled table on page 24: Date of study: 01-16 November 2004; CITATION_NUMBERS=[]; DETAILS_JSON={"cas_number":"131-57-7","citation":"","dose":"","duration":"","effect":"Unlabeled table on page 24: Date of study: 01-16 November 2004","endpoint":"","ingredient":"INCI name","loael_value":"","noael_unit":"","noael_value":"Date of study: 01-16 November 2004","page":24,"route":"","species":"","study_id":"sccp_o_078_noael_069"}
UnifiedCodex:SCCS_SHADOW:beta.noael_studies	-	67	-	-	-	-	-	SOURCE_SUBDIR=sccp_o_078; REPORT_TITLE=OPINION ON BENZOPHENONE-3 COLIPA N° S38; OPINION_NUMBER=SCCP/1069/06; COMMITTEE=SCCP; REPORT_DATE=19 December 2006; VALUE_TEXT=Guideline/method: Annex V to Dir. 67/548/EEC, Method B.31; OECD Guideline 414; EFFECT=Unlabeled table on page 24: Guideline/method: Annex V to Dir. 67/548/EEC, Method B.31; OECD Guideline 414; CITATION_NUMBERS=[]; DETAILS_JSON={"cas_number":"131-57-7","citation":"","dose":"","duration":"","effect":"Unlabeled table on page 24: Guideline/method: Annex V to Dir. 67/548/EEC, Method B.31; OECD Guideline 414","endpoint":"","ingredient":"INCI name","loael_value":"","noael_unit":"","noael_value":"Guideline/method: Annex V to Dir. 67/548/EEC, Method B.31; OECD Guideline 414","page":24,"route":"","species":"","study_id":"sccp_o_078_noael_070"}
UnifiedCodex:SCCS_SHADOW:beta.noael_studies	-	25	-	-	-	-	-	SOURCE_SUBDIR=sccp_o_078; REPORT_TITLE=OPINION ON BENZOPHENONE-3 COLIPA N° S38; OPINION_NUMBER=SCCP/1069/06; COMMITTEE=SCCP; REPORT_DATE=19 December 2006; VALUE_TEXT=Group size: 25 mated females per dosage group; EFFECT=Unlabeled table on page 24: Group size: 25 mated females per dosage group; CITATION_NUMBERS=[]; DETAILS_JSON={"cas_number":"131-57-7","citation":"","dose":"","duration":"","effect":"Unlabeled table on page 24: Group size: 25 mated females per dosage group","endpoint":"","ingredient":"INCI name","loael_value":"","noael_unit":"","noael_value":"Group size: 25 mated females per dosage group","page":24,"route":"","species":"","study_id":"sccp_o_078_noael_071"}
UnifiedCodex:SCCS_SHADOW:beta.noael_studies	-	-3	-	-	-	-	-	SOURCE_SUBDIR=sccp_o_078; REPORT_TITLE=OPINION ON BENZOPHENONE-3 COLIPA N° S38; OPINION_NUMBER=SCCP/1069/06; COMMITTEE=SCCP; REPORT_DATE=19 December 2006; VALUE_TEXT=Test substance: Benzophenone-3; EFFECT=Unlabeled table on page 24: Test substance: Benzophenone-3; CITATION_NUMBERS=[]; DETAILS_JSON={"cas_number":"131-57-7","citation":"","dose":"","duration":"","effect":"Unlabeled table on page 24: Test substance: Benzophenone-3","endpoint":"","ingredient":"INCI name","loael_value":"","noael_unit":"","noael_value":"Test substance: Benzophenone-3","page":24,"route":"","species":"","study_id":"sccp_o_078_noael_072"}
UnifiedCodex:SCCS_SHADOW:beta.noael_studies	-	99.8	%	-	-	-	-	SOURCE_SUBDIR=sccp_o_078; REPORT_TITLE=OPINION ON BENZOPHENONE-3 COLIPA N° S38; OPINION_NUMBER=SCCP/1069/06; COMMITTEE=SCCP; REPORT_DATE=19 December 2006; VALUE_TEXT=99.8; EFFECT=Unlabeled table on page 24: Purity: 99.8% (GC-FID); CITATION_NUMBERS=[]; DETAILS_JSON={"cas_number":"131-57-7","citation":"","dose":"","duration":"","effect":"Unlabeled table on page 24: Purity: 99.8% (GC-FID)","endpoint":"","ingredient":"INCI name","loael_value":"","noael_unit":"%","noael_value":"99.8","page":24,"route":"","species":"","study_id":"sccp_o_078_noael_073"}
UnifiedCodex:SCCS_SHADOW:beta.noael_studies	-	1000	mg/kg bw/day	-	-	-	-	SOURCE_SUBDIR=sccp_o_078; REPORT_TITLE=OPINION ON BENZOPHENONE-3 COLIPA N° S38; OPINION_NUMBER=SCCP/1069/06; COMMITTEE=SCCP; REPORT_DATE=19 December 2006; VALUE_TEXT=1000; DOSE=0, 40, 200 and 1000 mg/kg bw/day; EFFECT=Unlabeled table on page 24: Dosage levels: 0, 40, 200 and 1000 mg/kg bw/day; CITATION_NUMBERS=[]; DETAILS_JSON={"cas_number":"131-57-7","citation":"","dose":"0, 40, 200 and 1000 mg/kg bw/day","duration":"","effect":"Unlabeled table on page 24: Dosage levels: 0, 40, 200 and 1000 mg/kg bw/day","endpoint":"","ingredient":"INCI name","loael_value":"","noael_unit":"mg/kg bw/day","noael_value":"1000","page":24,"route":"","species":"","study_id":"sccp_o_078_noael_074"}
UnifiedCodex:SCCS_SHADOW:beta.noael_studies	-	25	-	-	-	-	-	SOURCE_SUBDIR=sccp_o_078; REPORT_TITLE=OPINION ON BENZOPHENONE-3 COLIPA N° S38; OPINION_NUMBER=SCCP/1069/06; COMMITTEE=SCCP; REPORT_DATE=19 December 2006; VALUE_TEXT=unclear:Unlabeled table on page 25: were only noted at a dosage level with overt parental toxicity. Consequently, the NOAEL for; EFFECT=Unlabeled table on page 25: were only noted at a dosage level with overt parental toxicity. Consequently, the NOAEL for; CITATION_NUMBERS=[]; DETAILS_JSON={"cas_number":"131-57-7","citation":"","dose":"","duration":"","effect":"Unlabeled table on page 25: were only noted at a dosage level with overt parental toxicity. Consequently, the NOAEL for","endpoint":"","ingredient":"INCI name","loael_value":"","noael_unit":"","noael_value":"unclear:Unlabeled table on page 25: were only noted at a dosage level with overt parental toxicity. Consequently, the NOAEL for","page":25,"route":"","species":"","study_id":"sccp_o_078_noael_076"}
UnifiedCodex:SCCS_SHADOW:beta.noael_studies	-	25	-	-	-	-	-	SOURCE_SUBDIR=sccp_o_078; REPORT_TITLE=OPINION ON BENZOPHENONE-3 COLIPA N° S38; OPINION_NUMBER=SCCP/1069/06; COMMITTEE=SCCP; REPORT_DATE=19 December 2006; VALUE_TEXT=unclear:Unlabeled table on page 25: reproduction parameter was noted and therefore, the NOAEL was in each case the highest; EFFECT=Unlabeled table on page 25: reproduction parameter was noted and therefore, the NOAEL was in each case the highest; CITATION_NUMBERS=[]; DETAILS_JSON={"cas_number":"131-57-7","citation":"","dose":"","duration":"","effect":"Unlabeled table on page 25: reproduction parameter was noted and therefore, the NOAEL was in each case the highest","endpoint":"","ingredient":"INCI name","loael_value":"","noael_unit":"","noael_value":"unclear:Unlabeled table on page 25: reproduction parameter was noted and therefore, the NOAEL was in each case the highest","page":25,"route":"","species":"","study_id":"sccp_o_078_noael_078"}
UnifiedCodex:SCCS_SHADOW:beta.noael_studies	-	35	-	-	oral	-	-	SOURCE_SUBDIR=sccp_o_078; REPORT_TITLE=OPINION ON BENZOPHENONE-3 COLIPA N° S38; OPINION_NUMBER=SCCP/1069/06; COMMITTEE=SCCP; REPORT_DATE=19 December 2006; VALUE_TEXT=unclear:Unlabeled table on page 35: reversible. Therefore, according to the submission, the oral NOAEL corresponds to; EFFECT=Unlabeled table on page 35: reversible. Therefore, according to the submission, the oral NOAEL corresponds to; CITATION_NUMBERS=[]; DETAILS_JSON={"cas_number":"131-57-7","citation":"","dose":"","duration":"","effect":"Unlabeled table on page 35: reversible. Therefore, according to the submission, the oral NOAEL corresponds to","endpoint":"","ingredient":"INCI name","loael_value":"","noael_unit":"","noael_value":"unclear:Unlabeled table on page 35: reversible. Therefore, according to the submission, the oral NOAEL corresponds to","page":35,"route":"oral","species":"","study_id":"sccp_o_078_noael_080"}
UnifiedCodex:SCCS_SHADOW:beta.noael_studies	-	36	-	-	-	-	-	SOURCE_SUBDIR=sccp_o_078; REPORT_TITLE=OPINION ON BENZOPHENONE-3 COLIPA N° S38; OPINION_NUMBER=SCCP/1069/06; COMMITTEE=SCCP; REPORT_DATE=19 December 2006; VALUE_TEXT=unclear:Unlabeled table on page 36: which also caused maternal toxicity, some skeletal aberrations were noted. The NOAEL-; EFFECT=Unlabeled table on page 36: which also caused maternal toxicity, some skeletal aberrations were noted. The NOAEL-; CITATION_NUMBERS=[]; DETAILS_JSON={"cas_number":"131-57-7","citation":"","dose":"","duration":"","effect":"Unlabeled table on page 36: which also caused maternal toxicity, some skeletal aberrations were noted. The NOAEL-","endpoint":"","ingredient":"INCI name","loael_value":"","noael_unit":"","noael_value":"unclear:Unlabeled table on page 36: which also caused maternal toxicity, some skeletal aberrations were noted. The NOAEL-","page":36,"route":"","species":"","study_id":"sccp_o_078_noael_082"}
UnifiedCodex:SCCS_SHADOW:beta.noael_studies	-	400	mg/kg bw/day	-	-	-	-	SOURCE_SUBDIR=sccp_o_078; REPORT_TITLE=OPINION ON BENZOPHENONE-3 COLIPA N° S38; OPINION_NUMBER=SCCP/1069/06; COMMITTEE=SCCP; REPORT_DATE=19 December 2006; VALUE_TEXT=400; DOSE=Out of these results, a NOAEL value of 400 mg/kg bw/day; EFFECT=Unlabeled table on page 36: "Continuous Breeding Protocol". Out of these results, a NOAEL value of 400 mg/kg bw/day; CITATION_NUMBERS=[]; DETAILS_JSON={"cas_number":"131-57-7","citation":"","dose":"Out of these results, a NOAEL value of 400 mg/kg bw/day","duration":"","effect":"Unlabeled table on page 36: \"Continuous Breeding Protocol\". Out of these results, a NOAEL value of 400 mg/kg bw/day","endpoint":"","ingredient":"INCI name","loael_value":"","noael_unit":"mg/kg bw/day","noael_value":"400","page":36,"route":"","species":"","study_id":"sccp_o_078_noael_083"}
UnifiedCodex:SCCS_SHADOW:beta.noael_studies	-	6	-	-	oral	-	-	SOURCE_SUBDIR=sccp_o_159; REPORT_TITLE=OPINION ON Benzophenone-3 COLIPA n° S38; OPINION_NUMBER=SCCP/1201/08; COMMITTEE=Scientific Committee on Consumer Products (SCCP); REPORT_DATE=16 December 2008; VALUE_TEXT=unclear:Unlabeled table on page 6: reversible. Therefore, according to the 2005-submission, the oral NOAEL corresponded to; EFFECT=Unlabeled table on page 6: reversible. Therefore, according to the 2005-submission, the oral NOAEL corresponded to; CITATION_NUMBERS=[]; DETAILS_JSON={"cas_number":"131-57-7","citation":"","dose":"","duration":"","effect":"Unlabeled table on page 6: reversible. Therefore, according to the 2005-submission, the oral NOAEL corresponded to","endpoint":"","ingredient":"2-hydroxy-4-methoxybenzophenone was submitted by COLIPA1 in December 2005.","loael_value":"","noael_unit":"","noael_value":"unclear:Unlabeled table on page 6: reversible. Therefore, according to the 2005-submission, the oral NOAEL corresponded to","page":6,"route":"oral","species":"","study_id":"sccp_o_159_noael_009"}
UnifiedCodex:SCCS_SHADOW:beta.noael_studies	-	200	mg/kg bw/day	-	dermal	-	-	SOURCE_SUBDIR=sccp_o_159; REPORT_TITLE=OPINION ON Benzophenone-3 COLIPA n° S38; OPINION_NUMBER=SCCP/1201/08; COMMITTEE=Scientific Committee on Consumer Products (SCCP); REPORT_DATE=16 December 2008; VALUE_TEXT=200; DOSE=Unlabeled table on page 6: dermal NOAEL of 200 mg/kg bw/day was put forward, on the assumption that deviations; EFFECT=Unlabeled table on page 6: dermal NOAEL of 200 mg/kg bw/day was put forward, on the assumption that deviations; CITATION_NUMBERS=[]; DETAILS_JSON={"cas_number":"131-57-7","citation":"","dose":"Unlabeled table on page 6: dermal NOAEL of 200 mg/kg bw/day was put forward, on the assumption that deviations","duration":"","effect":"Unlabeled table on page 6: dermal NOAEL of 200 mg/kg bw/day was put forward, on the assumption that deviations","endpoint":"","ingredient":"2-hydroxy-4-methoxybenzophenone was submitted by COLIPA1 in December 2005.","loael_value":"","noael_unit":"mg/kg bw/day","noael_value":"200","page":6,"route":"dermal","species":"","study_id":"sccp_o_159_noael_010"}
UnifiedCodex:SCCS_SHADOW:beta.noael_studies	-	56	-	-	-	-	-	SOURCE_SUBDIR=sccp_o_159; REPORT_TITLE=OPINION ON Benzophenone-3 COLIPA n° S38; OPINION_NUMBER=SCCP/1201/08; COMMITTEE=Scientific Committee on Consumer Products (SCCP); REPORT_DATE=16 December 2008; VALUE_TEXT=(cid:56) Toxicokinetic studies indicated that BP-3 was readily biotransformed into its three major; EFFECT=Unlabeled table on page 7: (cid:56) Toxicokinetic studies indicated that BP-3 was readily biotransformed into its three major; CITATION_NUMBERS=[]; DETAILS_JSON={"cas_number":"131-57-7","citation":"","dose":"","duration":"","effect":"Unlabeled table on page 7: (cid:56) Toxicokinetic studies indicated that BP-3 was readily biotransformed into its three major","endpoint":"","ingredient":"2-hydroxy-4-methoxybenzophenone was submitted by COLIPA1 in December 2005.","loael_value":"","noael_unit":"","noael_value":"(cid:56) Toxicokinetic studies indicated that BP-3 was readily biotransformed into its three major","page":7,"route":"","species":"","study_id":"sccp_o_159_noael_013"}
UnifiedCodex:SCCS_SHADOW:beta.noael_studies	-	56	-	-	-	-	-	SOURCE_SUBDIR=sccp_o_159; REPORT_TITLE=OPINION ON Benzophenone-3 COLIPA n° S38; OPINION_NUMBER=SCCP/1201/08; COMMITTEE=Scientific Committee on Consumer Products (SCCP); REPORT_DATE=16 December 2008; VALUE_TEXT=(cid:56) As far as the (photo)mutagenic/(photo)genotoxic potential of BP-3 was concerned, the; EFFECT=Unlabeled table on page 7: (cid:56) As far as the (photo)mutagenic/(photo)genotoxic potential of BP-3 was concerned, the; CITATION_NUMBERS=[]; DETAILS_JSON={"cas_number":"131-57-7","citation":"","dose":"","duration":"","effect":"Unlabeled table on page 7: (cid:56) As far as the (photo)mutagenic/(photo)genotoxic potential of BP-3 was concerned, the","endpoint":"","ingredient":"2-hydroxy-4-methoxybenzophenone was submitted by COLIPA1 in December 2005.","loael_value":"","noael_unit":"","noael_value":"(cid:56) As far as the (photo)mutagenic/(photo)genotoxic potential of BP-3 was concerned, the","page":7,"route":"","species":"","study_id":"sccp_o_159_noael_014"}
UnifiedCodex:SCCS_SHADOW:beta.noael_studies	-	-3	-	-	-	-	-	SOURCE_SUBDIR=sccp_o_159; REPORT_TITLE=OPINION ON Benzophenone-3 COLIPA n° S38; OPINION_NUMBER=SCCP/1201/08; COMMITTEE=Scientific Committee on Consumer Products (SCCP); REPORT_DATE=16 December 2008; VALUE_TEXT=The SCCP was unable to calculate the Margin of Safety for BP-3 as no scientifically; EFFECT=Unlabeled table on page 7: The SCCP was unable to calculate the Margin of Safety for BP-3 as no scientifically; CITATION_NUMBERS=[]; DETAILS_JSON={"cas_number":"131-57-7","citation":"","dose":"","duration":"","effect":"Unlabeled table on page 7: The SCCP was unable to calculate the Margin of Safety for BP-3 as no scientifically","endpoint":"","ingredient":"2-hydroxy-4-methoxybenzophenone was submitted by COLIPA1 in December 2005.","loael_value":"","noael_unit":"","noael_value":"The SCCP was unable to calculate the Margin of Safety for BP-3 as no scientifically","page":7,"route":"","species":"","study_id":"sccp_o_159_noael_015"}
UnifiedCodex:SCCS_SHADOW:beta.noael_studies	-	3.2	-	-	-	-	-	SOURCE_SUBDIR=sccp_o_159; REPORT_TITLE=OPINION ON Benzophenone-3 COLIPA n° S38; OPINION_NUMBER=SCCP/1201/08; COMMITTEE=Scientific Committee on Consumer Products (SCCP); REPORT_DATE=16 December 2008; VALUE_TEXT=3.2 DATA INTRODUCED; EFFECT=Unlabeled table on page 7: 3.2 DATA INTRODUCED; CITATION_NUMBERS=[]; DETAILS_JSON={"cas_number":"131-57-7","citation":"","dose":"","duration":"","effect":"Unlabeled table on page 7: 3.2 DATA INTRODUCED","endpoint":"","ingredient":"2-hydroxy-4-methoxybenzophenone was submitted by COLIPA1 in December 2005.","loael_value":"","noael_unit":"","noael_value":"3.2 DATA INTRODUCED","page":7,"route":"","species":"","study_id":"sccp_o_159_noael_016"}
UnifiedCodex:SCCS_SHADOW:beta.noael_studies	-	13	-	rat	-	-	-	SOURCE_SUBDIR=sccp_o_159; REPORT_TITLE=OPINION ON Benzophenone-3 COLIPA n° S38; OPINION_NUMBER=SCCP/1201/08; COMMITTEE=Scientific Committee on Consumer Products (SCCP); REPORT_DATE=16 December 2008; VALUE_TEXT=unclear:Unlabeled table on page 13: The available teratogenicity study in the rat generated a NOAEL-value for maternal and; EFFECT=Unlabeled table on page 13: The available teratogenicity study in the rat generated a NOAEL-value for maternal and; CITATION_NUMBERS=[]; DETAILS_JSON={"cas_number":"131-57-7","citation":"","dose":"","duration":"","effect":"Unlabeled table on page 13: The available teratogenicity study in the rat generated a NOAEL-value for maternal and","endpoint":"","ingredient":"2-hydroxy-4-methoxybenzophenone was submitted by COLIPA1 in December 2005.","loael_value":"","noael_unit":"","noael_value":"unclear:Unlabeled table on page 13: The available teratogenicity study in the rat generated a NOAEL-value for maternal and","page":13,"route":"","species":"rat","study_id":"sccp_o_159_noael_017"}
UnifiedCodex:SCCS_SHADOW:beta.noael_studies	-	6	%	-	-	-	-	SOURCE_SUBDIR=sccp_o_159; REPORT_TITLE=OPINION ON Benzophenone-3 COLIPA n° S38; OPINION_NUMBER=SCCP/1201/08; COMMITTEE=Scientific Committee on Consumer Products (SCCP); REPORT_DATE=16 December 2008; VALUE_TEXT=6; EFFECT=Unlabeled table on page 13: sunscreen (o/w or w/o) containing the maximum requested BP-3 concentration of 6%.; CITATION_NUMBERS=[]; DETAILS_JSON={"cas_number":"131-57-7","citation":"","dose":"","duration":"","effect":"Unlabeled table on page 13: sunscreen (o/w or w/o) containing the maximum requested BP-3 concentration of 6%.","endpoint":"","ingredient":"2-hydroxy-4-methoxybenzophenone was submitted by COLIPA1 in December 2005.","loael_value":"","noael_unit":"%","noael_value":"6","page":13,"route":"","species":"","study_id":"sccp_o_159_noael_019"}
UnifiedCodex:SCCS_SHADOW:beta.noael_studies	-	3.2	-	-	-	-	-	SOURCE_SUBDIR=sccp_o_159; REPORT_TITLE=OPINION ON Benzophenone-3 COLIPA n° S38; OPINION_NUMBER=SCCP/1201/08; COMMITTEE=Scientific Committee on Consumer Products (SCCP); REPORT_DATE=16 December 2008; VALUE_TEXT=section 3.2.4.; EFFECT=Unlabeled table on page 13: section 3.2.4.; CITATION_NUMBERS=[]; DETAILS_JSON={"cas_number":"131-57-7","citation":"","dose":"","duration":"","effect":"Unlabeled table on page 13: section 3.2.4.","endpoint":"","ingredient":"2-hydroxy-4-methoxybenzophenone was submitted by COLIPA1 in December 2005.","loael_value":"","noael_unit":"","noael_value":"section 3.2.4.","page":13,"route":"","species":"","study_id":"sccp_o_159_noael_021"}
UnifiedCodex:SCCS_SHADOW:beta.noael_studies	-	6	%	-	-	-	-	SOURCE_SUBDIR=sccp_o_159; REPORT_TITLE=OPINION ON Benzophenone-3 COLIPA n° S38; OPINION_NUMBER=SCCP/1201/08; COMMITTEE=Scientific Committee on Consumer Products (SCCP); REPORT_DATE=16 December 2008; VALUE_TEXT=6; EFFECT=Unlabeled table on page 13: For both requested use patterns (as a UV filter up to 6% in sunscreens and as a UV filter to; CITATION_NUMBERS=[]; DETAILS_JSON={"cas_number":"131-57-7","citation":"","dose":"","duration":"","effect":"Unlabeled table on page 13: For both requested use patterns (as a UV filter up to 6% in sunscreens and as a UV filter to","endpoint":"","ingredient":"2-hydroxy-4-methoxybenzophenone was submitted by COLIPA1 in December 2005.","loael_value":"","noael_unit":"%","noael_value":"6","page":13,"route":"","species":"","study_id":"sccp_o_159_noael_022"}
UnifiedCodex:SCCS_SHADOW:beta.noael_studies	-	0.5	%	-	-	-	-	SOURCE_SUBDIR=sccp_o_159; REPORT_TITLE=OPINION ON Benzophenone-3 COLIPA n° S38; OPINION_NUMBER=SCCP/1201/08; COMMITTEE=Scientific Committee on Consumer Products (SCCP); REPORT_DATE=16 December 2008; VALUE_TEXT=0.5; EFFECT=Unlabeled table on page 13: protect formulations up to 0.5% in all types of cosmetics), the MoS of BP-3 is above 100.; CITATION_NUMBERS=[]; DETAILS_JSON={"cas_number":"131-57-7","citation":"","dose":"","duration":"","effect":"Unlabeled table on page 13: protect formulations up to 0.5% in all types of cosmetics), the MoS of BP-3 is above 100.","endpoint":"","ingredient":"2-hydroxy-4-methoxybenzophenone was submitted by COLIPA1 in December 2005.","loael_value":"","noael_unit":"%","noael_value":"0.5","page":13,"route":"","species":"","study_id":"sccp_o_159_noael_023"}
UnifiedCodex:SCCS_SHADOW:beta.noael_studies	-	3.2	-	-	-	-	-	SOURCE_SUBDIR=sccp_o_159; REPORT_TITLE=OPINION ON Benzophenone-3 COLIPA n° S38; OPINION_NUMBER=SCCP/1201/08; COMMITTEE=Scientific Committee on Consumer Products (SCCP); REPORT_DATE=16 December 2008; VALUE_TEXT=under 3.2.3, support the statements of SCCP/1069/06 and do not introduce new discussion; EFFECT=Unlabeled table on page 13: under 3.2.3, support the statements of SCCP/1069/06 and do not introduce new discussion; CITATION_NUMBERS=[]; DETAILS_JSON={"cas_number":"131-57-7","citation":"","dose":"","duration":"","effect":"Unlabeled table on page 13: under 3.2.3, support the statements of SCCP/1069/06 and do not introduce new discussion","endpoint":"","ingredient":"2-hydroxy-4-methoxybenzophenone was submitted by COLIPA1 in December 2005.","loael_value":"","noael_unit":"","noael_value":"under 3.2.3, support the statements of SCCP/1069/06 and do not introduce new discussion","page":13,"route":"","species":"","study_id":"sccp_o_159_noael_024"}
UnifiedCodex:SCCS_SHADOW:beta.noael_studies	-	1000	ppm	-	-	-	-	SOURCE_SUBDIR=sccs_o_247; REPORT_TITLE=Final Opinion Scientific Committee on Consumer Safety SCCS OPINION on Benzophenone-3 (CAS No 131-57-7, EC No 205-031-5); OPINION_NUMBER=SCCS/1625/20; COMMITTEE=Scientific Committee on Consumer Safety (SCCS); REPORT_DATE=31 March 2021; VALUE_TEXT=1000; DOSE=Therefore, a decrease in testosterone, which is significant at 3000 ppm (see Fig 7) supports the plausibility of a decrease in spermatocytes numbers.; LOAEL_VALUE=67.9 mg /kg bw/day; EFFECT=reased in the tubules (see Fig 6); it is known that germinal cells are more sensitive than Sertoli cells to apoptosis (and Sertoli cells are less in numbers in the tubules). Moreover, it is well known that testosterone is needed for meiosis (De Gendt et al., 2004). Therefore, a decrease in testosterone, which is significant at 3000 ppm (see Fig 7) supports the plausibility of a decrease in spermatocytes numbers. Due to the effects on the ↓ of spermatocytes, the SCCS considered 3000 ppm as a LOAEL and therefore the NOAEL is 1000 ppm (67.9 mg /kg bw/day). This value will be used by the SCCS as a point of departure (POD) for the MoS calculation (see section 3.5 safety evaluation); CITATION_NUMBERS=[]; DETAILS_JSON={"cas_number":"131-57-7","citation":"","dose":"Therefore, a decrease in testosterone, which is significant at 3000 ppm (see Fig 7) supports the plausibility of a decrease in spermatocytes numbers.","duration":"","effect":"reased in the tubules (see Fig 6); it is known that germinal cells are more sensitive than Sertoli cells to apoptosis (and Sertoli cells are less in numbers in the tubules). Moreover, it is well known that testosterone is needed for meiosis (De Gendt et al., 2004). Therefore, a decrease in testosterone, which is significant at 3000 ppm (see Fig 7) supports the plausibility of a decrease in spermatocytes numbers. Due to the effects on the ↓ of spermatocytes, the SCCS considered 3000 ppm as a LOAEL and therefore the NOAEL is 1000 ppm (67.9 mg /kg bw/day). This value will be used by the SCCS as a point of departure (POD) for the MoS calculation (see section 3.5 safety evaluation)","endpoint":"","ingredient":", and this warrants further","loael_value":"67.9 mg /kg bw/day","noael_unit":"ppm","noael_value":"1000","page":39,"route":"","species":"","study_id":"sccs_o_247_noael_007"}
UnifiedCodex:SCCS_SHADOW:beta.noael_studies	-	>99	%	mouse	-	5 weeks	-	SOURCE_SUBDIR=sccs_o_247; REPORT_TITLE=Final Opinion Scientific Committee on Consumer Safety SCCS OPINION on Benzophenone-3 (CAS No 131-57-7, EC No 205-031-5); OPINION_NUMBER=SCCS/1625/20; COMMITTEE=Scientific Committee on Consumer Safety (SCCS); REPORT_DATE=31 March 2021; VALUE_TEXT=>99; DOSE=The lowest dose (30 µg/kg/d) was chosen on the basis of equivalence to the EFSA Tolerable Daily Intake (TDI), whereas 212 µg/kg/d for being close to the 95 percentile reported in human biomonitoring studies in pregnant women, and 3000 µg/kg/d for equivalence to the NOAEL used by EFSA as a point of departure (POD) to derive the TDI.; EFFECT=housed in polysulfone cages with food (which may have contained phytoestrogens) were exposed orally to BP-3 (>99% purity) from Gestational Day (GD) until the day before weaning (Lactational Day 21 or LD21) at 3 doses of BP-3 (30, 212 and 3000 µg/kg/d). The lowest dose (30 µg/kg/d) was chosen on the basis of equivalence to the EFSA Tolerable Daily Intake (TDI), whereas 212 µg/kg/d for being close to the 95 percentile reported in human biomonitoring studies in pregnant women, and 3000 µg/kg/d for equivalence to the NOAEL used by EFSA as a point of departure (POD) to derive the TDI. The authors noted that doses around 10 times higher are needed in rodents to produce equivalent levels in human urine, which means that the highest dose was still environmentally relevant. The study included 2 negative control groups: 1 vehicle group and a second group of nulliparous female mice, which were housed under the same conditions. At 5 weeks post-weaning (once mammary gland involution was complete), mice were killed and mammary glands (the lef; CITATION_NUMBERS=[]; DETAILS_JSON={"cas_number":"131-57-7","citation":"","dose":"The lowest dose (30 µg/kg/d) was chosen on the basis of equivalence to the EFSA Tolerable Daily Intake (TDI), whereas 212 µg/kg/d for being close to the 95 percentile reported in human biomonitoring studies in pregnant women, and 3000 µg/kg/d for equivalence to the NOAEL used by EFSA as a point of departure (POD) to derive the TDI.","duration":"5 weeks","effect":"housed in polysulfone cages with food (which may have contained phytoestrogens) were exposed orally to BP-3 (>99% purity) from Gestational Day (GD) until the day before weaning (Lactational Day 21 or LD21) at 3 doses of BP-3 (30, 212 and 3000 µg/kg/d). The lowest dose (30 µg/kg/d) was chosen on the basis of equivalence to the EFSA Tolerable Daily Intake (TDI), whereas 212 µg/kg/d for being close to the 95 percentile reported in human biomonitoring studies in pregnant women, and 3000 µg/kg/d for equivalence to the NOAEL used by EFSA as a point of departure (POD) to derive the TDI. The authors noted that doses around 10 times higher are needed in rodents to produce equivalent levels in human urine, which means that the highest dose was still environmentally relevant. The study included 2 negative control groups: 1 vehicle group and a second group of nulliparous female mice, which were housed under the same conditions. At 5 weeks post-weaning (once mammary gland involution was complete), mice were killed and mammary glands (the lef","endpoint":"","ingredient":", and this warrants further","loael_value":"","noael_unit":"%","noael_value":">99","page":40,"route":"","species":"mouse","study_id":"sccs_o_247_noael_008"}
UnifiedCodex:SCCS_SHADOW:beta.noael_studies	-	67.9	mg/kg bw/d	-	oral	-	-	SOURCE_SUBDIR=sccs_o_247; REPORT_TITLE=Final Opinion Scientific Committee on Consumer Safety SCCS OPINION on Benzophenone-3 (CAS No 131-57-7, EC No 205-031-5); OPINION_NUMBER=SCCS/1625/20; COMMITTEE=Scientific Committee on Consumer Safety (SCCS); REPORT_DATE=31 March 2021; VALUE_TEXT=67.9; DOSE=The NOAEL of 67.9 mg/kg bw/d has been derived from Nakamura et al.; EFFECT=al Opinion Opinion on Benzophenone-3 (CAS No 131-57-7, EC No 205-031-5) _________________________________________________________________________________________________________________ 47 whilst there are indications from some studies to suggest that BP-3 may have endocrine effects, it is not conclusive enough at present to enable deriving a new endocrine-related toxicological point of departure for use in safety assessment. 3.5 SAFETY EVALUATION (INCLUDING CALCULATION OF THE MOS) The SCCS has used the lowest NOAEL values among those obtained from different toxicological endpoints for the calculation of MoS (summarised in Annex-1). The NOAEL of 67.9 mg/kg bw/d has been derived from Nakamura et al. (2015) study. Because of the evidence for rapid and almost complete absorption of BP-3 from the oral route, the SCCS has not applied any adjustment for bioavailability to this NOAEL value. Details of the calculation of systemic exposure dose (SED) are presented in the Tables in Annex-2. The calculation of MoS for different product; CITATION_NUMBERS=[]; DETAILS_JSON={"cas_number":"131-57-7","citation":"","dose":"The NOAEL of 67.9 mg/kg bw/d has been derived from Nakamura et al.","duration":"","effect":"al Opinion Opinion on Benzophenone-3 (CAS No 131-57-7, EC No 205-031-5) _________________________________________________________________________________________________________________ 47 whilst there are indications from some studies to suggest that BP-3 may have endocrine effects, it is not conclusive enough at present to enable deriving a new endocrine-related toxicological point of departure for use in safety assessment. 3.5 SAFETY EVALUATION (INCLUDING CALCULATION OF THE MOS) The SCCS has used the lowest NOAEL values among those obtained from different toxicological endpoints for the calculation of MoS (summarised in Annex-1). The NOAEL of 67.9 mg/kg bw/d has been derived from Nakamura et al. (2015) study. Because of the evidence for rapid and almost complete absorption of BP-3 from the oral route, the SCCS has not applied any adjustment for bioavailability to this NOAEL value. Details of the calculation of systemic exposure dose (SED) are presented in the Tables in Annex-2. The calculation of MoS for different product","endpoint":"","ingredient":", and this warrants further","loael_value":"","noael_unit":"mg/kg bw/d","noael_value":"67.9","page":47,"route":"oral","species":"","study_id":"sccs_o_247_noael_009"}
UnifiedCodex:SCCS_SHADOW:beta.noael_studies	-	67.9	mg/kg bw/d	-	oral	-	-	SOURCE_SUBDIR=sccs_o_247; REPORT_TITLE=Final Opinion Scientific Committee on Consumer Safety SCCS OPINION on Benzophenone-3 (CAS No 131-57-7, EC No 205-031-5); OPINION_NUMBER=SCCS/1625/20; COMMITTEE=Scientific Committee on Consumer Safety (SCCS); REPORT_DATE=31 March 2021; VALUE_TEXT=67.9; DOSE=The NOAEL of 67.9 mg/kg bw/d has been derived from Nakamura et al.; EFFECT=_________________________________________________________ 47 whilst there are indications from some studies to suggest that BP-3 may have endocrine effects, it is not conclusive enough at present to enable deriving a new endocrine-related toxicological point of departure for use in safety assessment. 3.5 SAFETY EVALUATION (INCLUDING CALCULATION OF THE MOS) The SCCS has used the lowest NOAEL values among those obtained from different toxicological endpoints for the calculation of MoS (summarised in Annex-1). The NOAEL of 67.9 mg/kg bw/d has been derived from Nakamura et al. (2015) study. Because of the evidence for rapid and almost complete absorption of BP-3 from the oral route, the SCCS has not applied any adjustment for bioavailability to this NOAEL value. Details of the calculation of systemic exposure dose (SED) are presented in the Tables in Annex-2. The calculation of MoS for different product types are given in Table 3 below: Table 3: Calculation of Margin of Safety for different products containing BP-3 Products Con; CITATION_NUMBERS=[]; DETAILS_JSON={"cas_number":"131-57-7","citation":"","dose":"The NOAEL of 67.9 mg/kg bw/d has been derived from Nakamura et al.","duration":"","effect":"_________________________________________________________ 47 whilst there are indications from some studies to suggest that BP-3 may have endocrine effects, it is not conclusive enough at present to enable deriving a new endocrine-related toxicological point of departure for use in safety assessment. 3.5 SAFETY EVALUATION (INCLUDING CALCULATION OF THE MOS) The SCCS has used the lowest NOAEL values among those obtained from different toxicological endpoints for the calculation of MoS (summarised in Annex-1). The NOAEL of 67.9 mg/kg bw/d has been derived from Nakamura et al. (2015) study. Because of the evidence for rapid and almost complete absorption of BP-3 from the oral route, the SCCS has not applied any adjustment for bioavailability to this NOAEL value. Details of the calculation of systemic exposure dose (SED) are presented in the Tables in Annex-2. The calculation of MoS for different product types are given in Table 3 below: Table 3: Calculation of Margin of Safety for different products containing BP-3 Products Con","endpoint":"","ingredient":", and this warrants further","loael_value":"","noael_unit":"mg/kg bw/d","noael_value":"67.9","page":47,"route":"oral","species":"","study_id":"sccs_o_247_noael_010"}
UnifiedCodex:SCCS_SHADOW:beta.noael_studies	-	67.9	mg/kg bw/d	-	oral	-	-	SOURCE_SUBDIR=sccs_o_247; REPORT_TITLE=Final Opinion Scientific Committee on Consumer Safety SCCS OPINION on Benzophenone-3 (CAS No 131-57-7, EC No 205-031-5); OPINION_NUMBER=SCCS/1625/20; COMMITTEE=Scientific Committee on Consumer Safety (SCCS); REPORT_DATE=31 March 2021; VALUE_TEXT=67.9; DOSE=The NOAEL of 67.9 mg/kg bw/d has been derived from Nakamura et al.; EFFECT=toxicological point of departure for use in safety assessment. 3.5 SAFETY EVALUATION (INCLUDING CALCULATION OF THE MOS) The SCCS has used the lowest NOAEL values among those obtained from different toxicological endpoints for the calculation of MoS (summarised in Annex-1). The NOAEL of 67.9 mg/kg bw/d has been derived from Nakamura et al. (2015) study. Because of the evidence for rapid and almost complete absorption of BP-3 from the oral route, the SCCS has not applied any adjustment for bioavailability to this NOAEL value. Details of the calculation of systemic exposure dose (SED) are presented in the Tables in Annex-2. The calculation of MoS for different product types are given in Table 3 below: Table 3: Calculation of Margin of Safety for different products containing BP-3 Products Conc. Surface Systemic Exposure Dose (SED) mg/kg bw/d NOAEL* MOS Dermal Inhalation Oral Total UV cream 6% whole body 1.782 0 0 1.782 67.9 38 UV aerosolised spray 6% whole body 1.782 0.105 0 1.887 67.9 36 UV pump spray 6% whole body 1.782 0.00; CITATION_NUMBERS=[]; DETAILS_JSON={"cas_number":"131-57-7","citation":"","dose":"The NOAEL of 67.9 mg/kg bw/d has been derived from Nakamura et al.","duration":"","effect":"toxicological point of departure for use in safety assessment. 3.5 SAFETY EVALUATION (INCLUDING CALCULATION OF THE MOS) The SCCS has used the lowest NOAEL values among those obtained from different toxicological endpoints for the calculation of MoS (summarised in Annex-1). The NOAEL of 67.9 mg/kg bw/d has been derived from Nakamura et al. (2015) study. Because of the evidence for rapid and almost complete absorption of BP-3 from the oral route, the SCCS has not applied any adjustment for bioavailability to this NOAEL value. Details of the calculation of systemic exposure dose (SED) are presented in the Tables in Annex-2. The calculation of MoS for different product types are given in Table 3 below: Table 3: Calculation of Margin of Safety for different products containing BP-3 Products Conc. Surface Systemic Exposure Dose (SED) mg/kg bw/d NOAEL* MOS Dermal Inhalation Oral Total UV cream 6% whole body 1.782 0 0 1.782 67.9 38 UV aerosolised spray 6% whole body 1.782 0.105 0 1.887 67.9 36 UV pump spray 6% whole body 1.782 0.00","endpoint":"","ingredient":", and this warrants further","loael_value":"","noael_unit":"mg/kg bw/d","noael_value":"67.9","page":47,"route":"oral","species":"","study_id":"sccs_o_247_noael_011"}
UnifiedCodex:SCCS_SHADOW:beta.noael_studies	-	1625	-	rat	-	-	-	SOURCE_SUBDIR=sccs_o_247; REPORT_TITLE=Final Opinion Scientific Committee on Consumer Safety SCCS OPINION on Benzophenone-3 (CAS No 131-57-7, EC No 205-031-5); OPINION_NUMBER=SCCS/1625/20; COMMITTEE=Scientific Committee on Consumer Safety (SCCS); REPORT_DATE=31 March 2021; VALUE_TEXT=unclear:SCCS/1625/20 Final Opinion Opinion on Benzophenone-3 (CAS No 131-57-7, EC No 205-031-5) _________________________________________________________________________________________________________________ 48 were 0. 187 µg/ml in females and 0.238 µg/mL in males. Twenty-four hours after the first application, the median BP-3 levels in plasma were 0.047 µg/ml in females and 0.041 µg/ml in males. This clearly shows that the levels of BP-3 had exceeded the concentration measured in rats at the NOAEL. 3.6 DISCUSSION The 2008 SCCP Opinion (SCCP/1201/08) had noted a number of shortcomings in the data provided as part of the dossier assessed in an earlier Opinion (SCCP/1069/06). Despite this, the SCS agrees with the SCCP Opinion (2008) that the submission provides a reasonably well- structured overview of the available test descriptions and publications. Physicochemical properties BP-3is a widely used UV filter in cosmetic products. It is an off-white to light-yellow powder with a melting point of 62°C to 65°; EFFECT=SCCS/1625/20 Final Opinion Opinion on Benzophenone-3 (CAS No 131-57-7, EC No 205-031-5) _________________________________________________________________________________________________________________ 48 were 0. 187 µg/ml in females and 0.238 µg/mL in males. Twenty-four hours after the first application, the median BP-3 levels in plasma were 0.047 µg/ml in females and 0.041 µg/ml in males. This clearly shows that the levels of BP-3 had exceeded the concentration measured in rats at the NOAEL. 3.6 DISCUSSION The 2008 SCCP Opinion (SCCP/1201/08) had noted a number of shortcomings in the data provided as part of the dossier assessed in an earlier Opinion (SCCP/1069/06). Despite this, the SCS agrees with the SCCP Opinion (2008) that the submission provides a reasonably well- structured overview of the available test descriptions and publications. Physicochemical properties BP-3is a widely used UV filter in cosmetic products. It is an off-white to light-yellow powder with a melting point of 62°C to 65°; CITATION_NUMBERS=[]; DETAILS_JSON={"cas_number":"131-57-7","citation":"","dose":"","duration":"","effect":"SCCS/1625/20 Final Opinion Opinion on Benzophenone-3 (CAS No 131-57-7, EC No 205-031-5) _________________________________________________________________________________________________________________ 48 were 0. 187 µg/ml in females and 0.238 µg/mL in males. Twenty-four hours after the first application, the median BP-3 levels in plasma were 0.047 µg/ml in females and 0.041 µg/ml in males. This clearly shows that the levels of BP-3 had exceeded the concentration measured in rats at the NOAEL. 3.6 DISCUSSION The 2008 SCCP Opinion (SCCP/1201/08) had noted a number of shortcomings in the data provided as part of the dossier assessed in an earlier Opinion (SCCP/1069/06). Despite this, the SCS agrees with the SCCP Opinion (2008) that the submission provides a reasonably well- structured overview of the available test descriptions and publications. Physicochemical properties BP-3is a widely used UV filter in cosmetic products. It is an off-white to light-yellow powder with a melting point of 62°C to 65°","endpoint":"","ingredient":", and this warrants further","loael_value":"","noael_unit":"","noael_value":"unclear:SCCS/1625/20 Final Opinion Opinion on Benzophenone-3 (CAS No 131-57-7, EC No 205-031-5) _________________________________________________________________________________________________________________ 48 were 0. 187 µg/ml in females and 0.238 µg/mL in males. Twenty-four hours after the first application, the median BP-3 levels in plasma were 0.047 µg/ml in females and 0.041 µg/ml in males. This clearly shows that the levels of BP-3 had exceeded the concentration measured in rats at the NOAEL. 3.6 DISCUSSION The 2008 SCCP Opinion (SCCP/1201/08) had noted a number of shortcomings in the data provided as part of the dossier assessed in an earlier Opinion (SCCP/1069/06). Despite this, the SCS agrees with the SCCP Opinion (2008) that the submission provides a reasonably well- structured overview of the available test descriptions and publications. Physicochemical properties BP-3is a widely used UV filter in cosmetic products. It is an off-white to light-yellow powder with a melting point of 62°C to 65°","page":48,"route":"","species":"rat","study_id":"sccs_o_247_noael_013"}
UnifiedCodex:SCCS_SHADOW:beta.noael_studies	-	=411	mg/kg/ day	rat	oral	39 days	-	SOURCE_SUBDIR=sccs_o_247; REPORT_TITLE=Final Opinion Scientific Committee on Consumer Safety SCCS OPINION on Benzophenone-3 (CAS No 131-57-7, EC No 205-031-5); OPINION_NUMBER=SCCS/1625/20; COMMITTEE=Scientific Committee on Consumer Safety (SCCS); REPORT_DATE=31 March 2021; VALUE_TEXT== 411; DOSE=om GD6 during 39 days for F0 and then during 105 weeks for F1 Sacrifice at 14 weeks for 10 F1 rats ( m and f) at 0 and 10 000 ppm course of the study ↑ incidence of pigment in bone marrow at 10 000 ppm in m and f ↑ incidence of pigment in spleen at 10 000 ppm in m and f ↑ incidence of syncytial alteration in the liver of males at all doses ↑ inc...; EFFECT=om GD6 during 39 days for F0 and then during 105 weeks for F1 Sacrifice at 14 weeks for 10 F1 rats ( m and f) at 0 and 10 000 ppm course of the study ↑ incidence of pigment in bone marrow at 10 000 ppm in m and f ↑ incidence of pigment in spleen at 10 000 ppm in m and f ↑ incidence of syncytial alteration in the liver of males at all doses ↑ incidence of renal alterations at 3000 and 10 000 ppm in males ↑ incidence of osseous metaplasia in females at 10 000 ppm - 6 - Rats Oral Food 0, 3125,625,1 in males: NOAEL = 411 mg/kg/ day; CITATION_NUMBERS=[]; DETAILS_JSON={"cas_number":"131-57-7","citation":"","dose":"om GD6 during 39 days for F0 and then during 105 weeks for F1 Sacrifice at 14 weeks for 10 F1 rats ( m and f) at 0 and 10 000 ppm course of the study ↑ incidence of pigment in bone marrow at 10 000 ppm in m and f ↑ incidence of pigment in spleen at 10 000 ppm in m and f ↑ incidence of syncytial alteration in the liver of males at all doses ↑ inc...","duration":"39 days","effect":"om GD6 during 39 days for F0 and then during 105 weeks for F1 Sacrifice at 14 weeks for 10 F1 rats ( m and f) at 0 and 10 000 ppm course of the study ↑ incidence of pigment in bone marrow at 10 000 ppm in m and f ↑ incidence of pigment in spleen at 10 000 ppm in m and f ↑ incidence of syncytial alteration in the liver of males at all doses ↑ incidence of renal alterations at 3000 and 10 000 ppm in males ↑ incidence of osseous metaplasia in females at 10 000 ppm - 6 - Rats Oral Food 0, 3125,625,1 in males: NOAEL = 411 mg/kg/ day","endpoint":"","ingredient":", and this warrants further","loael_value":"","noael_unit":"mg/kg/ day","noael_value":"= 411","page":65,"route":"oral","species":"rat","study_id":"sccs_o_247_noael_028"}
UnifiedCodex:SCCS_SHADOW:beta.noael_studies	-	3	-	-	-	-	-	SOURCE_SUBDIR=sccs_o_247; REPORT_TITLE=Final Opinion Scientific Committee on Consumer Safety SCCS OPINION on Benzophenone-3 (CAS No 131-57-7, EC No 205-031-5); OPINION_NUMBER=SCCS/1625/20; COMMITTEE=Scientific Committee on Consumer Safety (SCCS); REPORT_DATE=31 March 2021; VALUE_TEXT=unclear:Table 3: Calculation of Margin of Safety for different products containing BP-3: Products | Conc. | Surface | Systemic Exposure Dose (SED) mg/kg bw/d | NOAEL* | MOS; DOSE=Products | Conc. | Surface | Systemic Exposure Dose (SED) mg/kg bw/d | NOAEL* | MOS; EFFECT=Table 3: Calculation of Margin of Safety for different products containing BP-3: Products | Conc. | Surface | Systemic Exposure Dose (SED) mg/kg bw/d | NOAEL* | MOS; CITATION_NUMBERS=[]; DETAILS_JSON={"cas_number":"131-57-7","citation":"","dose":"Products | Conc. | Surface | Systemic Exposure Dose (SED) mg/kg bw/d | NOAEL* | MOS","duration":"","effect":"Table 3: Calculation of Margin of Safety for different products containing BP-3: Products | Conc. | Surface | Systemic Exposure Dose (SED) mg/kg bw/d | NOAEL* | MOS","endpoint":"","ingredient":", and this warrants further","loael_value":"","noael_unit":"","noael_value":"unclear:Table 3: Calculation of Margin of Safety for different products containing BP-3: Products | Conc. | Surface | Systemic Exposure Dose (SED) mg/kg bw/d | NOAEL* | MOS","page":47,"route":"","species":"","study_id":"sccs_o_247_noael_033"}
UnifiedCodex:SCCS_SHADOW:beta.noael_studies	-	6	%	-	-	-	-	SOURCE_SUBDIR=sccs_o_247; REPORT_TITLE=Final Opinion Scientific Committee on Consumer Safety SCCS OPINION on Benzophenone-3 (CAS No 131-57-7, EC No 205-031-5); OPINION_NUMBER=SCCS/1625/20; COMMITTEE=Scientific Committee on Consumer Safety (SCCS); REPORT_DATE=31 March 2021; VALUE_TEXT=6; EFFECT=Table 3: Calculation of Margin of Safety for different products containing BP-3: UV cream | 6% | whole body | 1.782 | 0 | 0 | 1.782 | 67.9 | 38; CITATION_NUMBERS=[]; DETAILS_JSON={"cas_number":"131-57-7","citation":"","dose":"","duration":"","effect":"Table 3: Calculation of Margin of Safety for different products containing BP-3: UV cream | 6% | whole body | 1.782 | 0 | 0 | 1.782 | 67.9 | 38","endpoint":"","ingredient":", and this warrants further","loael_value":"","noael_unit":"%","noael_value":"6","page":47,"route":"","species":"","study_id":"sccs_o_247_noael_034"}
UnifiedCodex:SCCS_SHADOW:beta.noael_studies	-	6	%	-	-	-	-	SOURCE_SUBDIR=sccs_o_247; REPORT_TITLE=Final Opinion Scientific Committee on Consumer Safety SCCS OPINION on Benzophenone-3 (CAS No 131-57-7, EC No 205-031-5); OPINION_NUMBER=SCCS/1625/20; COMMITTEE=Scientific Committee on Consumer Safety (SCCS); REPORT_DATE=31 March 2021; VALUE_TEXT=6; EFFECT=Table 3: Calculation of Margin of Safety for different products containing BP-3: UV aerosolised spray | 6% | whole body | 1.782 | 0.105 | 0 | 1.887 | 67.9 | 36; CITATION_NUMBERS=[]; DETAILS_JSON={"cas_number":"131-57-7","citation":"","dose":"","duration":"","effect":"Table 3: Calculation of Margin of Safety for different products containing BP-3: UV aerosolised spray | 6% | whole body | 1.782 | 0.105 | 0 | 1.887 | 67.9 | 36","endpoint":"","ingredient":", and this warrants further","loael_value":"","noael_unit":"%","noael_value":"6","page":47,"route":"","species":"","study_id":"sccs_o_247_noael_035"}
UnifiedCodex:SCCS_SHADOW:beta.noael_studies	-	6	%	-	-	-	-	SOURCE_SUBDIR=sccs_o_247; REPORT_TITLE=Final Opinion Scientific Committee on Consumer Safety SCCS OPINION on Benzophenone-3 (CAS No 131-57-7, EC No 205-031-5); OPINION_NUMBER=SCCS/1625/20; COMMITTEE=Scientific Committee on Consumer Safety (SCCS); REPORT_DATE=31 March 2021; VALUE_TEXT=6; EFFECT=Table 3: Calculation of Margin of Safety for different products containing BP-3: UV pump spray | 6% | whole body | 1.782 | 0.001053 | 0 | 1.783 | 67.9 | 38; CITATION_NUMBERS=[]; DETAILS_JSON={"cas_number":"131-57-7","citation":"","dose":"","duration":"","effect":"Table 3: Calculation of Margin of Safety for different products containing BP-3: UV pump spray | 6% | whole body | 1.782 | 0.001053 | 0 | 1.783 | 67.9 | 38","endpoint":"","ingredient":", and this warrants further","loael_value":"","noael_unit":"%","noael_value":"6","page":47,"route":"","species":"","study_id":"sccs_o_247_noael_036"}
UnifiedCodex:SCCS_SHADOW:beta.noael_studies	-	6	%	-	-	-	-	SOURCE_SUBDIR=sccs_o_247; REPORT_TITLE=Final Opinion Scientific Committee on Consumer Safety SCCS OPINION on Benzophenone-3 (CAS No 131-57-7, EC No 205-031-5); OPINION_NUMBER=SCCS/1625/20; COMMITTEE=Scientific Committee on Consumer Safety (SCCS); REPORT_DATE=31 March 2021; VALUE_TEXT=6; EFFECT=Table 3: Calculation of Margin of Safety for different products containing BP-3: UV face cream | 6% | face | 0.152 | 0 | 0 | 0.152 | 67.9 | 447; CITATION_NUMBERS=[]; DETAILS_JSON={"cas_number":"131-57-7","citation":"","dose":"","duration":"","effect":"Table 3: Calculation of Margin of Safety for different products containing BP-3: UV face cream | 6% | face | 0.152 | 0 | 0 | 0.152 | 67.9 | 447","endpoint":"","ingredient":", and this warrants further","loael_value":"","noael_unit":"%","noael_value":"6","page":47,"route":"","species":"","study_id":"sccs_o_247_noael_037"}
UnifiedCodex:SCCS_SHADOW:beta.noael_studies	-	6	%	-	-	-	-	SOURCE_SUBDIR=sccs_o_247; REPORT_TITLE=Final Opinion Scientific Committee on Consumer Safety SCCS OPINION on Benzophenone-3 (CAS No 131-57-7, EC No 205-031-5); OPINION_NUMBER=SCCS/1625/20; COMMITTEE=Scientific Committee on Consumer Safety (SCCS); REPORT_DATE=31 March 2021; VALUE_TEXT=6; EFFECT=Table 3: Calculation of Margin of Safety for different products containing BP-3: UV hand cream | 6% | hand | 0.214 | 0 | 0 | 0.214 | 67.9 | 317; CITATION_NUMBERS=[]; DETAILS_JSON={"cas_number":"131-57-7","citation":"","dose":"","duration":"","effect":"Table 3: Calculation of Margin of Safety for different products containing BP-3: UV hand cream | 6% | hand | 0.214 | 0 | 0 | 0.214 | 67.9 | 317","endpoint":"","ingredient":", and this warrants further","loael_value":"","noael_unit":"%","noael_value":"6","page":47,"route":"","species":"","study_id":"sccs_o_247_noael_038"}
UnifiedCodex:SCCS_SHADOW:beta.noael_studies	-	0.5	%	-	-	-	-	SOURCE_SUBDIR=sccs_o_247; REPORT_TITLE=Final Opinion Scientific Committee on Consumer Safety SCCS OPINION on Benzophenone-3 (CAS No 131-57-7, EC No 205-031-5); OPINION_NUMBER=SCCS/1625/20; COMMITTEE=Scientific Committee on Consumer Safety (SCCS); REPORT_DATE=31 March 2021; VALUE_TEXT=0.50; EFFECT=Table 3: Calculation of Margin of Safety for different products containing BP-3: Non-UV** | 0.50% | whole body | 0.116 | 0 | 0 | 0.116 | 67.9 | 585; CITATION_NUMBERS=[]; DETAILS_JSON={"cas_number":"131-57-7","citation":"","dose":"","duration":"","effect":"Table 3: Calculation of Margin of Safety for different products containing BP-3: Non-UV** | 0.50% | whole body | 0.116 | 0 | 0 | 0.116 | 67.9 | 585","endpoint":"","ingredient":", and this warrants further","loael_value":"","noael_unit":"%","noael_value":"0.50","page":47,"route":"","species":"","study_id":"sccs_o_247_noael_039"}
UnifiedCodex:SCCS_SHADOW:beta.noael_studies	-	6	%	-	-	-	-	SOURCE_SUBDIR=sccs_o_247; REPORT_TITLE=Final Opinion Scientific Committee on Consumer Safety SCCS OPINION on Benzophenone-3 (CAS No 131-57-7, EC No 205-031-5); OPINION_NUMBER=SCCS/1625/20; COMMITTEE=Scientific Committee on Consumer Safety (SCCS); REPORT_DATE=31 March 2021; VALUE_TEXT=6; EFFECT=Table 3: Calculation of Margin of Safety for different products containing BP-3: Lipstick | 6% | lips | 0.000 | 0 | 0.054 | 0.054 | 67.9 | 1257; CITATION_NUMBERS=[]; DETAILS_JSON={"cas_number":"131-57-7","citation":"","dose":"","duration":"","effect":"Table 3: Calculation of Margin of Safety for different products containing BP-3: Lipstick | 6% | lips | 0.000 | 0 | 0.054 | 0.054 | 67.9 | 1257","endpoint":"","ingredient":", and this warrants further","loael_value":"","noael_unit":"%","noael_value":"6","page":47,"route":"","species":"","study_id":"sccs_o_247_noael_040"}
UnifiedCodex:SCCS_SHADOW:beta.noael_studies	-	62	-	-	-	-	-	SOURCE_SUBDIR=sccs_o_247; REPORT_TITLE=Final Opinion Scientific Committee on Consumer Safety SCCS OPINION on Benzophenone-3 (CAS No 131-57-7, EC No 205-031-5); OPINION_NUMBER=SCCS/1625/20; COMMITTEE=Scientific Committee on Consumer Safety (SCCS); REPORT_DATE=31 March 2021; VALUE_TEXT=unclear:Unlabeled table on page 62: Number and reference | Species Strain Model | Routes | Dose, Exposure period | Group size | Outcomes reported | NOAEL/ LOAEL derived by the authors | SCCS Comments; DOSE=Number and reference | Species Strain Model | Routes | Dose, Exposure period | Group size | Outcomes reported | NOAEL/ LOAEL derived by the authors | SCCS Comments; EFFECT=Unlabeled table on page 62: Number and reference | Species Strain Model | Routes | Dose, Exposure period | Group size | Outcomes reported | NOAEL/ LOAEL derived by the authors | SCCS Comments; CITATION_NUMBERS=[]; DETAILS_JSON={"cas_number":"131-57-7","citation":"","dose":"Number and reference | Species Strain Model | Routes | Dose, Exposure period | Group size | Outcomes reported | NOAEL/ LOAEL derived by the authors | SCCS Comments","duration":"","effect":"Unlabeled table on page 62: Number and reference | Species Strain Model | Routes | Dose, Exposure period | Group size | Outcomes reported | NOAEL/ LOAEL derived by the authors | SCCS Comments","endpoint":"","ingredient":", and this warrants further","loael_value":"","noael_unit":"","noael_value":"unclear:Unlabeled table on page 62: Number and reference | Species Strain Model | Routes | Dose, Exposure period | Group size | Outcomes reported | NOAEL/ LOAEL derived by the authors | SCCS Comments","page":62,"route":"","species":"","study_id":"sccs_o_247_noael_041"}
UnifiedCodex:SCCS_SHADOW:beta.noael_studies	-	3448.2	mg/kg/day	-	-	-	-	SOURCE_SUBDIR=sccs_o_247; REPORT_TITLE=Final Opinion Scientific Committee on Consumer Safety SCCS OPINION on Benzophenone-3 (CAS No 131-57-7, EC No 205-031-5); OPINION_NUMBER=SCCS/1625/20; COMMITTEE=Scientific Committee on Consumer Safety (SCCS); REPORT_DATE=31 March 2021; VALUE_TEXT=3448.2; DOSE=Unlabeled table on page 63: and 3448.2 mg/kg/day . from GD6 to PND 23 Observatio n on PND1 and PND 23 | and relative) in female and male offspring and blood biochemical factors in the high dose (≥10,000 ppm) groups | fetuses, or sex ratios between the control and treated groups; ↑ ovaries and uterine weights (absolute and relative) at 1000 ppm b...; LOAEL_VALUE=68 mg /kg bw/day; EFFECT=Unlabeled table on page 63: and 3448.2 mg/kg/day . from GD6 to PND 23 Observatio n on PND1 and PND 23 | and relative) in female and male offspring and blood biochemical factors in the high dose (≥10,000 ppm) groups | fetuses, or sex ratios between the control and treated groups; ↑ ovaries and uterine weights (absolute and relative) at 1000 ppm but not at higher doses | doses (dose related) ↑ apoptic cells in seminiferous tubules at 10 000 ppm and above (not dose related) Limited ↓ testo level at 3000 and 25 000 ppm In female offspring at PND23 Delayed follicular development at 10 000 and 50 000 ppm | system (↓ AGD, ↓ spermatocytes production and/or quality…) Due to the effects on the ↓ of spermatocyte which may be due to an ED effects of BP-3 SCCS considered 3000 ppm as a LOAEL and therefore the NOAEL should be 1000 ppm ( 68 mg /kg bw/day); CITATION_NUMBERS=[]; DETAILS_JSON={"cas_number":"131-57-7","citation":"","dose":"Unlabeled table on page 63: and 3448.2 mg/kg/day . from GD6 to PND 23 Observatio n on PND1 and PND 23 | and relative) in female and male offspring and blood biochemical factors in the high dose (≥10,000 ppm) groups | fetuses, or sex ratios between the control and treated groups; ↑ ovaries and uterine weights (absolute and relative) at 1000 ppm b...","duration":"","effect":"Unlabeled table on page 63: and 3448.2 mg/kg/day . from GD6 to PND 23 Observatio n on PND1 and PND 23 | and relative) in female and male offspring and blood biochemical factors in the high dose (≥10,000 ppm) groups | fetuses, or sex ratios between the control and treated groups; ↑ ovaries and uterine weights (absolute and relative) at 1000 ppm but not at higher doses | doses (dose related) ↑ apoptic cells in seminiferous tubules at 10 000 ppm and above (not dose related) Limited ↓ testo level at 3000 and 25 000 ppm In female offspring at PND23 Delayed follicular development at 10 000 and 50 000 ppm | system (↓ AGD, ↓ spermatocytes production and/or quality…) Due to the effects on the ↓ of spermatocyte which may be due to an ED effects of BP-3 SCCS considered 3000 ppm as a LOAEL and therefore the NOAEL should be 1000 ppm ( 68 mg /kg bw/day)","endpoint":"","ingredient":", and this warrants further","loael_value":"68 mg /kg bw/day","noael_unit":"mg/kg/day","noael_value":"3448.2","page":63,"route":"","species":"","study_id":"sccs_o_247_noael_045"}
UnifiedCodex:SCCS_SHADOW:beta.noael_studies	-	=411	mg/kg/ day	rat	oral	-	-	SOURCE_SUBDIR=sccs_o_247; REPORT_TITLE=Final Opinion Scientific Committee on Consumer Safety SCCS OPINION on Benzophenone-3 (CAS No 131-57-7, EC No 205-031-5); OPINION_NUMBER=SCCS/1625/20; COMMITTEE=Scientific Committee on Consumer Safety (SCCS); REPORT_DATE=31 March 2021; VALUE_TEXT== 411; DOSE=Unlabeled table on page 65: - 6 - | Rats | Oral Food | 0, 3125,625,1 | in males: | NOAEL = 411 mg/kg/ day; EFFECT=Unlabeled table on page 65: - 6 - | Rats | Oral Food | 0, 3125,625,1 | in males: | NOAEL = 411 mg/kg/ day; CITATION_NUMBERS=[]; DETAILS_JSON={"cas_number":"131-57-7","citation":"","dose":"Unlabeled table on page 65: - 6 - | Rats | Oral Food | 0, 3125,625,1 | in males: | NOAEL = 411 mg/kg/ day","duration":"","effect":"Unlabeled table on page 65: - 6 - | Rats | Oral Food | 0, 3125,625,1 | in males: | NOAEL = 411 mg/kg/ day","endpoint":"","ingredient":", and this warrants further","loael_value":"","noael_unit":"mg/kg/ day","noael_value":"= 411","page":65,"route":"oral","species":"rat","study_id":"sccs_o_247_noael_049"}
UnifiedCodex:SCCS_SHADOW:beta.noael_studies	-	=364	mg/kg bw/day	mouse	dermal	-	-	SOURCE_SUBDIR=sccs_o_247; REPORT_TITLE=Final Opinion Scientific Committee on Consumer Safety SCCS OPINION on Benzophenone-3 (CAS No 131-57-7, EC No 205-031-5); OPINION_NUMBER=SCCS/1625/20; COMMITTEE=Scientific Committee on Consumer Safety (SCCS); REPORT_DATE=31 March 2021; VALUE_TEXT== 364; DOSE=Unlabeled table on page 67: -11- | Mice | Dermal | 0, 22.8, 45.5, 91, | ↓ in epididymal sperm density | NOAEL = 364 mg/kg bw/day | In view of the effects on sperm; EFFECT=Unlabeled table on page 67: -11- | Mice | Dermal | 0, 22.8, 45.5, 91, | ↓ in epididymal sperm density | NOAEL = 364 mg/kg bw/day | In view of the effects on sperm; CITATION_NUMBERS=[]; DETAILS_JSON={"cas_number":"131-57-7","citation":"","dose":"Unlabeled table on page 67: -11- | Mice | Dermal | 0, 22.8, 45.5, 91, | ↓ in epididymal sperm density | NOAEL = 364 mg/kg bw/day | In view of the effects on sperm","duration":"","effect":"Unlabeled table on page 67: -11- | Mice | Dermal | 0, 22.8, 45.5, 91, | ↓ in epididymal sperm density | NOAEL = 364 mg/kg bw/day | In view of the effects on sperm","endpoint":"","ingredient":", and this warrants further","loael_value":"","noael_unit":"mg/kg bw/day","noael_value":"= 364","page":67,"route":"dermal","species":"mouse","study_id":"sccs_o_247_noael_054"}
UnifiedCodex:SCCS_SHADOW:beta.noael_studies	dermal absorption	200	mg/kg bw/day	rat	dermal	-	dermal absorption	SOURCE_SUBDIR=sccp_o_159; REPORT_TITLE=OPINION ON Benzophenone-3 COLIPA n° S38; OPINION_NUMBER=SCCP/1201/08; COMMITTEE=Scientific Committee on Consumer Products (SCCP); REPORT_DATE=16 December 2008; VALUE_TEXT=200; DOSE=9.9% [mean (3.1%) + 2 SD (2*3.4%)] Applied dose (sunscreen):; EFFECT=SCCP/1201/08 Opinion on benzophenone-3 13 3.2.4 Safety evaluation (including calculation of the MoS) BP-3 as a UV-filter in sunscreens up to 6% Dermal absorption (6% formulation): 9.9% [mean (3.1%) + 2 SD (2*3.4%)] Applied dose (sunscreen): 18 g/day Typical human body weight: 60 kg No observed effect level NOAEL (terato-rat): 200 mg/kg bw/day Systemic exposure dose (SED) = (18.103 mg/day * 6/100 * 9.9/100) / 60 kg = 1.78 mg/kg bw/day MoS = NOAEL / SED = 112 BP-3 as a UV-filter at 0.5% to protect cosmetic formulations against sunlight Dermal absorption (2% formulation): 8.0% [mean (4.0%) + 2 SD (2*2.0%)] Applied dose (all cosmetic products): 17.79 g/day Typical human body weight: 60 kg No observed effect level NOAEL (terato-rat): 200 mg/kg bw/day Systemic exposure dose (SED) = (17.79.103 mg/day * 0.5/100 * 8.0/100); CITATION_NUMBERS=[]; DETAILS_JSON={"cas_number":"131-57-7","citation":"","dose":"9.9% [mean (3.1%) + 2 SD (2*3.4%)] Applied dose (sunscreen):","duration":"","effect":"SCCP/1201/08 Opinion on benzophenone-3 13 3.2.4 Safety evaluation (including calculation of the MoS) BP-3 as a UV-filter in sunscreens up to 6% Dermal absorption (6% formulation): 9.9% [mean (3.1%) + 2 SD (2*3.4%)] Applied dose (sunscreen): 18 g/day Typical human body weight: 60 kg No observed effect level NOAEL (terato-rat): 200 mg/kg bw/day Systemic exposure dose (SED) = (18.103 mg/day * 6/100 * 9.9/100) / 60 kg = 1.78 mg/kg bw/day MoS = NOAEL / SED = 112 BP-3 as a UV-filter at 0.5% to protect cosmetic formulations against sunlight Dermal absorption (2% formulation): 8.0% [mean (4.0%) + 2 SD (2*2.0%)] Applied dose (all cosmetic products): 17.79 g/day Typical human body weight: 60 kg No observed effect level NOAEL (terato-rat): 200 mg/kg bw/day Systemic exposure dose (SED) = (17.79.103 mg/day * 0.5/100 * 8.0/100)","endpoint":"dermal absorption","ingredient":"2-hydroxy-4-methoxybenzophenone was submitted by COLIPA1 in December 2005.","loael_value":"","noael_unit":"mg/kg bw/day","noael_value":"200","page":13,"route":"dermal","species":"rat","study_id":"sccp_o_159_noael_004"}
UnifiedCodex:SCCS_SHADOW:beta.noael_studies	dermal absorption	=1.78	mg/kg bw/day	rat	dermal	-	dermal absorption	SOURCE_SUBDIR=sccp_o_159; REPORT_TITLE=OPINION ON Benzophenone-3 COLIPA n° S38; OPINION_NUMBER=SCCP/1201/08; COMMITTEE=Scientific Committee on Consumer Products (SCCP); REPORT_DATE=16 December 2008; VALUE_TEXT== 1.78; DOSE=9.9% [mean (3.1%) + 2 SD (2*3.4%)] Applied dose (sunscreen):; EFFECT=SCCP/1201/08 Opinion on benzophenone-3 13 3.2.4 Safety evaluation (including calculation of the MoS) BP-3 as a UV-filter in sunscreens up to 6% Dermal absorption (6% formulation): 9.9% [mean (3.1%) + 2 SD (2*3.4%)] Applied dose (sunscreen): 18 g/day Typical human body weight: 60 kg No observed effect level NOAEL (terato-rat): 200 mg/kg bw/day Systemic exposure dose (SED) = (18.103 mg/day * 6/100 * 9.9/100) / 60 kg = 1.78 mg/kg bw/day MoS = NOAEL / SED = 112 BP-3 as a UV-filter at 0.5% to protect cosmetic formulations against sunlight Dermal absorption (2% formulation): 8.0% [mean (4.0%) + 2 SD (2*2.0%)] Applied dose (all cosmetic products): 17.79 g/day Typical human body weight: 60 kg No observed effect level NOAEL (terato-rat): 200 mg/kg bw/day Systemic exposure dose (SED) = (17.79.103 mg/day * 0.5/100 * 8.0/100) / 60 kg = 0.119 mg/kg bw/day MoS = NOAEL / SED = 1686 3.2.5 Discussion A detailed discussion on the general toxicological profile of B; CITATION_NUMBERS=[]; DETAILS_JSON={"cas_number":"131-57-7","citation":"","dose":"9.9% [mean (3.1%) + 2 SD (2*3.4%)] Applied dose (sunscreen):","duration":"","effect":"SCCP/1201/08 Opinion on benzophenone-3 13 3.2.4 Safety evaluation (including calculation of the MoS) BP-3 as a UV-filter in sunscreens up to 6% Dermal absorption (6% formulation): 9.9% [mean (3.1%) + 2 SD (2*3.4%)] Applied dose (sunscreen): 18 g/day Typical human body weight: 60 kg No observed effect level NOAEL (terato-rat): 200 mg/kg bw/day Systemic exposure dose (SED) = (18.103 mg/day * 6/100 * 9.9/100) / 60 kg = 1.78 mg/kg bw/day MoS = NOAEL / SED = 112 BP-3 as a UV-filter at 0.5% to protect cosmetic formulations against sunlight Dermal absorption (2% formulation): 8.0% [mean (4.0%) + 2 SD (2*2.0%)] Applied dose (all cosmetic products): 17.79 g/day Typical human body weight: 60 kg No observed effect level NOAEL (terato-rat): 200 mg/kg bw/day Systemic exposure dose (SED) = (17.79.103 mg/day * 0.5/100 * 8.0/100) / 60 kg = 0.119 mg/kg bw/day MoS = NOAEL / SED = 1686 3.2.5 Discussion A detailed discussion on the general toxicological profile of B","endpoint":"dermal absorption","ingredient":"2-hydroxy-4-methoxybenzophenone was submitted by COLIPA1 in December 2005.","loael_value":"","noael_unit":"mg/kg bw/day","noael_value":"= 1.78","page":13,"route":"dermal","species":"rat","study_id":"sccp_o_159_noael_005"}
UnifiedCodex:SCCS_SHADOW:beta.noael_studies	dermal absorption	200	mg/kg bw/day	rat	dermal	-	dermal absorption	SOURCE_SUBDIR=sccp_o_159; REPORT_TITLE=OPINION ON Benzophenone-3 COLIPA n° S38; OPINION_NUMBER=SCCP/1201/08; COMMITTEE=Scientific Committee on Consumer Products (SCCP); REPORT_DATE=16 December 2008; VALUE_TEXT=200; DOSE=(2*3.4%)] Applied dose (sunscreen):; EFFECT=(2*3.4%)] Applied dose (sunscreen): 18 g/day Typical human body weight: 60 kg No observed effect level NOAEL (terato-rat): 200 mg/kg bw/day Systemic exposure dose (SED) = (18.103 mg/day * 6/100 * 9.9/100) / 60 kg = 1.78 mg/kg bw/day MoS = NOAEL / SED = 112 BP-3 as a UV-filter at 0.5% to protect cosmetic formulations against sunlight Dermal absorption (2% formulation): 8.0% [mean (4.0%) + 2 SD (2*2.0%)] Applied dose (all cosmetic products): 17.79 g/day Typical human body weight: 60 kg No observed effect level NOAEL (terato-rat): 200 mg/kg bw/day Systemic exposure dose (SED) = (17.79.103 mg/day * 0.5/100 * 8.0/100) / 60 kg = 0.119 mg/kg bw/day MoS = NOAEL / SED = 1686 3.2.5 Discussion A detailed discussion on the general toxicological profile of BP-3 was given in SCCP/1069/06 and taken over under section 3.1 of the current opinion. The major shortcoming in the dossier was the absence of a sound dermal absorption study, allowing the calculation of the Margin of Safety for the UV-filter. The newly provided in vitro dermal; CITATION_NUMBERS=[]; DETAILS_JSON={"cas_number":"131-57-7","citation":"","dose":"(2*3.4%)] Applied dose (sunscreen):","duration":"","effect":"(2*3.4%)] Applied dose (sunscreen): 18 g/day Typical human body weight: 60 kg No observed effect level NOAEL (terato-rat): 200 mg/kg bw/day Systemic exposure dose (SED) = (18.103 mg/day * 6/100 * 9.9/100) / 60 kg = 1.78 mg/kg bw/day MoS = NOAEL / SED = 112 BP-3 as a UV-filter at 0.5% to protect cosmetic formulations against sunlight Dermal absorption (2% formulation): 8.0% [mean (4.0%) + 2 SD (2*2.0%)] Applied dose (all cosmetic products): 17.79 g/day Typical human body weight: 60 kg No observed effect level NOAEL (terato-rat): 200 mg/kg bw/day Systemic exposure dose (SED) = (17.79.103 mg/day * 0.5/100 * 8.0/100) / 60 kg = 0.119 mg/kg bw/day MoS = NOAEL / SED = 1686 3.2.5 Discussion A detailed discussion on the general toxicological profile of BP-3 was given in SCCP/1069/06 and taken over under section 3.1 of the current opinion. The major shortcoming in the dossier was the absence of a sound dermal absorption study, allowing the calculation of the Margin of Safety for the UV-filter. The newly provided in vitro dermal","endpoint":"dermal absorption","ingredient":"2-hydroxy-4-methoxybenzophenone was submitted by COLIPA1 in December 2005.","loael_value":"","noael_unit":"mg/kg bw/day","noael_value":"200","page":13,"route":"dermal","species":"rat","study_id":"sccp_o_159_noael_006"}
UnifiedCodex:SCCS_SHADOW:beta.noael_studies	dermal absorption	=0.119	mg/kg bw/day	rat	dermal	-	dermal absorption	SOURCE_SUBDIR=sccp_o_159; REPORT_TITLE=OPINION ON Benzophenone-3 COLIPA n° S38; OPINION_NUMBER=SCCP/1201/08; COMMITTEE=Scientific Committee on Consumer Products (SCCP); REPORT_DATE=16 December 2008; VALUE_TEXT== 0.119; DOSE=temic exposure dose (SED) = (18.103 mg/day * 6/100 * 9.9/100) / 60 kg = 1.78 mg/kg bw/day MoS = NOAEL / SED = 112 BP-3 as a UV-filter at 0.5% to protect cosmetic formulations against sunlight Dermal absorption (2% formulation):; EFFECT=temic exposure dose (SED) = (18.103 mg/day * 6/100 * 9.9/100) / 60 kg = 1.78 mg/kg bw/day MoS = NOAEL / SED = 112 BP-3 as a UV-filter at 0.5% to protect cosmetic formulations against sunlight Dermal absorption (2% formulation): 8.0% [mean (4.0%) + 2 SD (2*2.0%)] Applied dose (all cosmetic products): 17.79 g/day Typical human body weight: 60 kg No observed effect level NOAEL (terato-rat): 200 mg/kg bw/day Systemic exposure dose (SED) = (17.79.103 mg/day * 0.5/100 * 8.0/100) / 60 kg = 0.119 mg/kg bw/day MoS = NOAEL / SED = 1686 3.2.5 Discussion A detailed discussion on the general toxicological profile of BP-3 was given in SCCP/1069/06 and taken over under section 3.1 of the current opinion. The major shortcoming in the dossier was the absence of a sound dermal absorption study, allowing the calculation of the Margin of Safety for the UV-filter. The newly provided in vitro dermal absorption study is considered scientifically acceptable and shows a mean dermal absorption level of 19.3 µg/cm² or 3.1% of the applied dose fo; CITATION_NUMBERS=[]; DETAILS_JSON={"cas_number":"131-57-7","citation":"","dose":"temic exposure dose (SED) = (18.103 mg/day * 6/100 * 9.9/100) / 60 kg = 1.78 mg/kg bw/day MoS = NOAEL / SED = 112 BP-3 as a UV-filter at 0.5% to protect cosmetic formulations against sunlight Dermal absorption (2% formulation):","duration":"","effect":"temic exposure dose (SED) = (18.103 mg/day * 6/100 * 9.9/100) / 60 kg = 1.78 mg/kg bw/day MoS = NOAEL / SED = 112 BP-3 as a UV-filter at 0.5% to protect cosmetic formulations against sunlight Dermal absorption (2% formulation): 8.0% [mean (4.0%) + 2 SD (2*2.0%)] Applied dose (all cosmetic products): 17.79 g/day Typical human body weight: 60 kg No observed effect level NOAEL (terato-rat): 200 mg/kg bw/day Systemic exposure dose (SED) = (17.79.103 mg/day * 0.5/100 * 8.0/100) / 60 kg = 0.119 mg/kg bw/day MoS = NOAEL / SED = 1686 3.2.5 Discussion A detailed discussion on the general toxicological profile of BP-3 was given in SCCP/1069/06 and taken over under section 3.1 of the current opinion. The major shortcoming in the dossier was the absence of a sound dermal absorption study, allowing the calculation of the Margin of Safety for the UV-filter. The newly provided in vitro dermal absorption study is considered scientifically acceptable and shows a mean dermal absorption level of 19.3 µg/cm² or 3.1% of the applied dose fo","endpoint":"dermal absorption","ingredient":"2-hydroxy-4-methoxybenzophenone was submitted by COLIPA1 in December 2005.","loael_value":"","noael_unit":"mg/kg bw/day","noael_value":"= 0.119","page":13,"route":"dermal","species":"rat","study_id":"sccp_o_159_noael_007"}
UnifiedCodex:SCCS_SHADOW:beta.noael_studies	dermal absorption	19.3	µg/cm	-	dermal	-	dermal absorption	SOURCE_SUBDIR=sccp_o_159; REPORT_TITLE=OPINION ON Benzophenone-3 COLIPA n° S38; OPINION_NUMBER=SCCP/1201/08; COMMITTEE=Scientific Committee on Consumer Products (SCCP); REPORT_DATE=16 December 2008; VALUE_TEXT=19.3; DOSE=Unlabeled table on page 13: and shows a mean dermal absorption level of 19.3 µg/cm² or 3.1% of the applied dose for a; EFFECT=Unlabeled table on page 13: and shows a mean dermal absorption level of 19.3 µg/cm² or 3.1% of the applied dose for a; CITATION_NUMBERS=[]; DETAILS_JSON={"cas_number":"131-57-7","citation":"","dose":"Unlabeled table on page 13: and shows a mean dermal absorption level of 19.3 µg/cm² or 3.1% of the applied dose for a","duration":"","effect":"Unlabeled table on page 13: and shows a mean dermal absorption level of 19.3 µg/cm² or 3.1% of the applied dose for a","endpoint":"dermal absorption","ingredient":"2-hydroxy-4-methoxybenzophenone was submitted by COLIPA1 in December 2005.","loael_value":"","noael_unit":"µg/cm","noael_value":"19.3","page":13,"route":"dermal","species":"","study_id":"sccp_o_159_noael_018"}
UnifiedCodex:SCCS_SHADOW:beta.noael_studies	dermal absorption	67.9	mg/kg bw/d	-	dermal	-	dermal absorption	SOURCE_SUBDIR=sccs_o_247; REPORT_TITLE=Final Opinion Scientific Committee on Consumer Safety SCCS OPINION on Benzophenone-3 (CAS No 131-57-7, EC No 205-031-5); OPINION_NUMBER=SCCS/1625/20; COMMITTEE=Scientific Committee on Consumer Safety (SCCS); REPORT_DATE=31 March 2021; VALUE_TEXT=67.9; DOSE=ered 3000 ppm as a LOAEL and 1000 ppm as the NOAEL (67.9 mg /kg bw/day) Safety evaluation (including calculation of the MoS) The SCCS has a dermal absorption of 9.9% [mean (3.1%) + 2 SD (2*3.4%)] for the use of BP-3 as a UV filter at 6% for the calculation of the systemic exposure dose (SED) and the margin of safety (MoS) for sunscreen products.; LOAEL_VALUE=67.9 mg /kg bw/day; EFFECT=ered 3000 ppm as a LOAEL and 1000 ppm as the NOAEL (67.9 mg /kg bw/day) Safety evaluation (including calculation of the MoS) The SCCS has a dermal absorption of 9.9% [mean (3.1%) + 2 SD (2*3.4%)] for the use of BP-3 as a UV filter at 6% for the calculation of the systemic exposure dose (SED) and the margin of safety (MoS) for sunscreen products. For other cosmetic products, the SCCS has used a dermal absorption of 8% [mean (4%) + 2 SD (2*2%)]. For the calculation of the margin of safety (MoS), the SCCS has used a NOAEL of 67.9 mg/kg bw/d from the Nakamura et al. (2015) study. The SCCS has estimated the margin of safety (MoS) as 38 for the use of BP-3 at a concentration of 6% as a UV-filter in sunscreens for the whole body application (in the form of cream/lotion or pump spray, and 36 for sunscreen propellant spray), and 447 for the face, 317 for the hand and 1257 for lipstick application. The MoS has been estimated at 585 for the use of BP-3 at 0.5% to protect cosmetic formulations against sunlight. The SCCS assessment did not c; CITATION_NUMBERS=[]; DETAILS_JSON={"cas_number":"131-57-7","citation":"","dose":"ered 3000 ppm as a LOAEL and 1000 ppm as the NOAEL (67.9 mg /kg bw/day) Safety evaluation (including calculation of the MoS) The SCCS has a dermal absorption of 9.9% [mean (3.1%) + 2 SD (2*3.4%)] for the use of BP-3 as a UV filter at 6% for the calculation of the systemic exposure dose (SED) and the margin of safety (MoS) for sunscreen products.","duration":"","effect":"ered 3000 ppm as a LOAEL and 1000 ppm as the NOAEL (67.9 mg /kg bw/day) Safety evaluation (including calculation of the MoS) The SCCS has a dermal absorption of 9.9% [mean (3.1%) + 2 SD (2*3.4%)] for the use of BP-3 as a UV filter at 6% for the calculation of the systemic exposure dose (SED) and the margin of safety (MoS) for sunscreen products. For other cosmetic products, the SCCS has used a dermal absorption of 8% [mean (4%) + 2 SD (2*2%)]. For the calculation of the margin of safety (MoS), the SCCS has used a NOAEL of 67.9 mg/kg bw/d from the Nakamura et al. (2015) study. The SCCS has estimated the margin of safety (MoS) as 38 for the use of BP-3 at a concentration of 6% as a UV-filter in sunscreens for the whole body application (in the form of cream/lotion or pump spray, and 36 for sunscreen propellant spray), and 447 for the face, 317 for the hand and 1257 for lipstick application. The MoS has been estimated at 585 for the use of BP-3 at 0.5% to protect cosmetic formulations against sunlight. The SCCS assessment did not c","endpoint":"dermal absorption","ingredient":", and this warrants further","loael_value":"67.9 mg /kg bw/day","noael_unit":"mg/kg bw/d","noael_value":"67.9","page":51,"route":"dermal","species":"","study_id":"sccs_o_247_noael_017"}
UnifiedCodex:SCCS_SHADOW:beta.noael_studies	developmental toxicity	200	mg/kg bw/day	-	-	prenatal	developmental toxicity	SOURCE_SUBDIR=sccp_o_078; REPORT_TITLE=OPINION ON BENZOPHENONE-3 COLIPA N° S38; OPINION_NUMBER=SCCP/1069/06; COMMITTEE=SCCP; REPORT_DATE=19 December 2006; VALUE_TEXT=200; DOSE=ransient salivation immediately after dosing; stained/reddish coloured urine; reduced food consumption and body weight (gain); slightly increased rates of foetuses/litter with skeletal variations (incomplete ossification of different skull bones and cervical arch, supernumerary 14th ribs(s)) and as a consequence increased rates of total variatio...; EFFECT=ransient salivation immediately after dosing; stained/reddish coloured urine; reduced food consumption and body weight (gain); slightly increased rates of foetuses/litter with skeletal variations (incomplete ossification of different skull bones and cervical arch, supernumerary 14th ribs(s)) and as a consequence increased rates of total variations; no test-substance related effects on gestational parameters The performing laboratory concludes that Benzophenone-3 did not display any teratogenic effect and that the NOAEL for maternal and prenatal developmental toxicity is 200 mg/kg bw/day. Ref.: 11; CITATION=Ref.: 11; CITATION_NUMBERS=[11]; REFERENCE=Ref.: 11; DETAILS_JSON={"cas_number":"131-57-7","citation":"Ref.: 11","dose":"ransient salivation immediately after dosing; stained/reddish coloured urine; reduced food consumption and body weight (gain); slightly increased rates of foetuses/litter with skeletal variations (incomplete ossification of different skull bones and cervical arch, supernumerary 14th ribs(s)) and as a consequence increased rates of total variatio...","duration":"prenatal","effect":"ransient salivation immediately after dosing; stained/reddish coloured urine; reduced food consumption and body weight (gain); slightly increased rates of foetuses/litter with skeletal variations (incomplete ossification of different skull bones and cervical arch, supernumerary 14th ribs(s)) and as a consequence increased rates of total variations; no test-substance related effects on gestational parameters The performing laboratory concludes that Benzophenone-3 did not display any teratogenic effect and that the NOAEL for maternal and prenatal developmental toxicity is 200 mg/kg bw/day. Ref.: 11","endpoint":"developmental toxicity","ingredient":"INCI name","loael_value":"","noael_unit":"mg/kg bw/day","noael_value":"200","page":24,"route":"","species":"","study_id":"sccp_o_078_noael_017"}
UnifiedCodex:SCCS_SHADOW:beta.noael_studies	developmental toxicity	24	-	-	-	prenatal	developmental toxicity	SOURCE_SUBDIR=sccp_o_078; REPORT_TITLE=OPINION ON BENZOPHENONE-3 COLIPA N° S38; OPINION_NUMBER=SCCP/1069/06; COMMITTEE=SCCP; REPORT_DATE=19 December 2006; VALUE_TEXT=unclear:Unlabeled table on page 24: effect and that the NOAEL for maternal and prenatal developmental toxicity is; EFFECT=Unlabeled table on page 24: effect and that the NOAEL for maternal and prenatal developmental toxicity is; CITATION_NUMBERS=[]; DETAILS_JSON={"cas_number":"131-57-7","citation":"","dose":"","duration":"prenatal","effect":"Unlabeled table on page 24: effect and that the NOAEL for maternal and prenatal developmental toxicity is","endpoint":"developmental toxicity","ingredient":"INCI name","loael_value":"","noael_unit":"","noael_value":"unclear:Unlabeled table on page 24: effect and that the NOAEL for maternal and prenatal developmental toxicity is","page":24,"route":"","species":"","study_id":"sccp_o_078_noael_066"}
UnifiedCodex:SCCS_SHADOW:beta.noael_studies	developmental toxicity	200	mg/kg bw/d	-	-	prenatal	developmental toxicity	SOURCE_SUBDIR=sccp_o_078; REPORT_TITLE=OPINION ON BENZOPHENONE-3 COLIPA N° S38; OPINION_NUMBER=SCCP/1069/06; COMMITTEE=SCCP; REPORT_DATE=19 December 2006; VALUE_TEXT=200; DOSE=Unlabeled table on page 25: toxicity, the achieved NOAEL was 200 mg/kg bw/d for maternal and prenatal developmental; EFFECT=Unlabeled table on page 25: toxicity, the achieved NOAEL was 200 mg/kg bw/d for maternal and prenatal developmental; CITATION_NUMBERS=[]; DETAILS_JSON={"cas_number":"131-57-7","citation":"","dose":"Unlabeled table on page 25: toxicity, the achieved NOAEL was 200 mg/kg bw/d for maternal and prenatal developmental","duration":"prenatal","effect":"Unlabeled table on page 25: toxicity, the achieved NOAEL was 200 mg/kg bw/d for maternal and prenatal developmental","endpoint":"developmental toxicity","ingredient":"INCI name","loael_value":"","noael_unit":"mg/kg bw/d","noael_value":"200","page":25,"route":"","species":"","study_id":"sccp_o_078_noael_079"}
UnifiedCodex:SCCS_SHADOW:beta.noael_studies	developmental toxicity	200	mg/kg bw/day	rat	dermal	developmental	developmental toxicity	SOURCE_SUBDIR=sccp_o_159; REPORT_TITLE=OPINION ON Benzophenone-3 COLIPA n° S38; OPINION_NUMBER=SCCP/1201/08; COMMITTEE=Scientific Committee on Consumer Products (SCCP); REPORT_DATE=16 December 2008; VALUE_TEXT=200; DOSE=The newly provided in vitro dermal absorption study is considered scientifically acceptable and shows a mean dermal absorption level of 19.3 µg/cm² or 3.1% of the applied dose for a sunscreen (o/w or w/o) containing the maximum requested BP-3 concentration of 6%.; EFFECT=der section 3.1 of the current opinion. The major shortcoming in the dossier was the absence of a sound dermal absorption study, allowing the calculation of the Margin of Safety for the UV-filter. The newly provided in vitro dermal absorption study is considered scientifically acceptable and shows a mean dermal absorption level of 19.3 µg/cm² or 3.1% of the applied dose for a sunscreen (o/w or w/o) containing the maximum requested BP-3 concentration of 6%. The available teratogenicity study in the rat generated a NOAEL-value for maternal and developmental toxicity of 200 mg/kg bw/day, which was used to calculate the MoS under section 3.2.4. For both requested use patterns (as a UV filter up to 6% in sunscreens and as a UV filter to protect formulations up to 0.5% in all types of cosmetics), the MoS of BP-3 is above 100. The additional literature references provided in the most recent submission and summarized under 3.2.3, support the statements of SCCP/1069/06 and do not introduce new discussion points.; CITATION_NUMBERS=[]; DETAILS_JSON={"cas_number":"131-57-7","citation":"","dose":"The newly provided in vitro dermal absorption study is considered scientifically acceptable and shows a mean dermal absorption level of 19.3 µg/cm² or 3.1% of the applied dose for a sunscreen (o/w or w/o) containing the maximum requested BP-3 concentration of 6%.","duration":"developmental","effect":"der section 3.1 of the current opinion. The major shortcoming in the dossier was the absence of a sound dermal absorption study, allowing the calculation of the Margin of Safety for the UV-filter. The newly provided in vitro dermal absorption study is considered scientifically acceptable and shows a mean dermal absorption level of 19.3 µg/cm² or 3.1% of the applied dose for a sunscreen (o/w or w/o) containing the maximum requested BP-3 concentration of 6%. The available teratogenicity study in the rat generated a NOAEL-value for maternal and developmental toxicity of 200 mg/kg bw/day, which was used to calculate the MoS under section 3.2.4. For both requested use patterns (as a UV filter up to 6% in sunscreens and as a UV filter to protect formulations up to 0.5% in all types of cosmetics), the MoS of BP-3 is above 100. The additional literature references provided in the most recent submission and summarized under 3.2.3, support the statements of SCCP/1069/06 and do not introduce new discussion points.","endpoint":"developmental toxicity","ingredient":"2-hydroxy-4-methoxybenzophenone was submitted by COLIPA1 in December 2005.","loael_value":"","noael_unit":"mg/kg bw/day","noael_value":"200","page":13,"route":"dermal","species":"rat","study_id":"sccp_o_159_noael_008"}
UnifiedCodex:SCCS_SHADOW:beta.noael_studies	developmental toxicity	7	-	-	-	developmental	developmental toxicity	SOURCE_SUBDIR=sccp_o_159; REPORT_TITLE=OPINION ON Benzophenone-3 COLIPA n° S38; OPINION_NUMBER=SCCP/1201/08; COMMITTEE=Scientific Committee on Consumer Products (SCCP); REPORT_DATE=16 December 2008; VALUE_TEXT=unclear:Unlabeled table on page 7: skeletal aberrations were noted. The NOAEL-value for maternal and developmental; EFFECT=Unlabeled table on page 7: skeletal aberrations were noted. The NOAEL-value for maternal and developmental; CITATION_NUMBERS=[]; DETAILS_JSON={"cas_number":"131-57-7","citation":"","dose":"","duration":"developmental","effect":"Unlabeled table on page 7: skeletal aberrations were noted. The NOAEL-value for maternal and developmental","endpoint":"developmental toxicity","ingredient":"2-hydroxy-4-methoxybenzophenone was submitted by COLIPA1 in December 2005.","loael_value":"","noael_unit":"","noael_value":"unclear:Unlabeled table on page 7: skeletal aberrations were noted. The NOAEL-value for maternal and developmental","page":7,"route":"","species":"","study_id":"sccp_o_159_noael_011"}
UnifiedCodex:SCCS_SHADOW:beta.noael_studies	developmental toxicity	200	mg/kg bw/day	-	-	developmental	developmental toxicity	SOURCE_SUBDIR=sccp_o_159; REPORT_TITLE=OPINION ON Benzophenone-3 COLIPA n° S38; OPINION_NUMBER=SCCP/1201/08; COMMITTEE=Scientific Committee on Consumer Products (SCCP); REPORT_DATE=16 December 2008; VALUE_TEXT=200; DOSE=Unlabeled table on page 13: developmental toxicity of 200 mg/kg bw/day, which was used to calculate the MoS under; EFFECT=Unlabeled table on page 13: developmental toxicity of 200 mg/kg bw/day, which was used to calculate the MoS under; CITATION_NUMBERS=[]; DETAILS_JSON={"cas_number":"131-57-7","citation":"","dose":"Unlabeled table on page 13: developmental toxicity of 200 mg/kg bw/day, which was used to calculate the MoS under","duration":"developmental","effect":"Unlabeled table on page 13: developmental toxicity of 200 mg/kg bw/day, which was used to calculate the MoS under","endpoint":"developmental toxicity","ingredient":"2-hydroxy-4-methoxybenzophenone was submitted by COLIPA1 in December 2005.","loael_value":"","noael_unit":"mg/kg bw/day","noael_value":"200","page":13,"route":"","species":"","study_id":"sccp_o_159_noael_020"}
UnifiedCodex:SCCS_SHADOW:beta.noael_studies	developmental toxicity	3000	ppm	-	-	developmental	developmental toxicity	SOURCE_SUBDIR=sccs_o_247; REPORT_TITLE=Final Opinion Scientific Committee on Consumer Safety SCCS OPINION on Benzophenone-3 (CAS No 131-57-7, EC No 205-031-5); OPINION_NUMBER=SCCS/1625/20; COMMITTEE=Scientific Committee on Consumer Safety (SCCS); REPORT_DATE=31 March 2021; VALUE_TEXT=3000; DOSE=However, on PND 4, pup body weights (male, female, and both) in the 10000 ppm exposure groups were statistically significantly decreased (both sexes approximately 5% lower) compared to the control group.; EFFECT=ere not statistically significantly different across the exposure groups on PND 1. However, on PND 4, pup body weights (male, female, and both) in the 10000 ppm exposure groups were statistically significantly decreased (both sexes approximately 5% lower) compared to the control group. This response was generally observed over subsequent pre-weaning weights, and by PND 21 combined live pup weight at this dose was 8% lower than control. Conclusion from the applicant Under the conditions of this study, the maternal NOAEL is 3000 ppm (206-478 mg/kg bw/day), based on reduced body weight gain during GD 6–9 and lactation day 4–21. The developmental NOEL is considered as 3000 ppm (206-478 mg/kg bw/day) based on impaired postnatal bodyweight performance at 10000 ppm (660-1609 mg/kg bw/day). (National Toxicology Program, 2020) Guidelines/Guidances: NTP Modified One-Generation study design GLP: FDA GLP; CITATION_NUMBERS=[]; DETAILS_JSON={"cas_number":"131-57-7","citation":"","dose":"However, on PND 4, pup body weights (male, female, and both) in the 10000 ppm exposure groups were statistically significantly decreased (both sexes approximately 5% lower) compared to the control group.","duration":"developmental","effect":"ere not statistically significantly different across the exposure groups on PND 1. However, on PND 4, pup body weights (male, female, and both) in the 10000 ppm exposure groups were statistically significantly decreased (both sexes approximately 5% lower) compared to the control group. This response was generally observed over subsequent pre-weaning weights, and by PND 21 combined live pup weight at this dose was 8% lower than control. Conclusion from the applicant Under the conditions of this study, the maternal NOAEL is 3000 ppm (206-478 mg/kg bw/day), based on reduced body weight gain during GD 6–9 and lactation day 4–21. The developmental NOEL is considered as 3000 ppm (206-478 mg/kg bw/day) based on impaired postnatal bodyweight performance at 10000 ppm (660-1609 mg/kg bw/day). (National Toxicology Program, 2020) Guidelines/Guidances: NTP Modified One-Generation study design GLP: FDA GLP","endpoint":"developmental toxicity","ingredient":", and this warrants further","loael_value":"","noael_unit":"ppm","noael_value":"3000","page":27,"route":"","species":"","study_id":"sccs_o_247_noael_005"}
UnifiedCodex:SCCS_SHADOW:beta.noael_studies	developmental toxicity	3000	ppm	-	-	developmental	developmental toxicity	SOURCE_SUBDIR=sccs_o_247; REPORT_TITLE=Final Opinion Scientific Committee on Consumer Safety SCCS OPINION on Benzophenone-3 (CAS No 131-57-7, EC No 205-031-5); OPINION_NUMBER=SCCS/1625/20; COMMITTEE=Scientific Committee on Consumer Safety (SCCS); REPORT_DATE=31 March 2021; VALUE_TEXT=3000; DOSE=, and both) in the 10000 ppm exposure groups were statistically significantly decreased (both sexes approximately 5% lower) compared to the control group.; EFFECT=, and both) in the 10000 ppm exposure groups were statistically significantly decreased (both sexes approximately 5% lower) compared to the control group. This response was generally observed over subsequent pre-weaning weights, and by PND 21 combined live pup weight at this dose was 8% lower than control. Conclusion from the applicant Under the conditions of this study, the maternal NOAEL is 3000 ppm (206-478 mg/kg bw/day), based on reduced body weight gain during GD 6–9 and lactation day 4–21. The developmental NOEL is considered as 3000 ppm (206-478 mg/kg bw/day) based on impaired postnatal bodyweight performance at 10000 ppm (660-1609 mg/kg bw/day). (National Toxicology Program, 2020) Guidelines/Guidances: NTP Modified One-Generation study design GLP: FDA GLP; CITATION_NUMBERS=[]; DETAILS_JSON={"cas_number":"131-57-7","citation":"","dose":", and both) in the 10000 ppm exposure groups were statistically significantly decreased (both sexes approximately 5% lower) compared to the control group.","duration":"developmental","effect":", and both) in the 10000 ppm exposure groups were statistically significantly decreased (both sexes approximately 5% lower) compared to the control group. This response was generally observed over subsequent pre-weaning weights, and by PND 21 combined live pup weight at this dose was 8% lower than control. Conclusion from the applicant Under the conditions of this study, the maternal NOAEL is 3000 ppm (206-478 mg/kg bw/day), based on reduced body weight gain during GD 6–9 and lactation day 4–21. The developmental NOEL is considered as 3000 ppm (206-478 mg/kg bw/day) based on impaired postnatal bodyweight performance at 10000 ppm (660-1609 mg/kg bw/day). (National Toxicology Program, 2020) Guidelines/Guidances: NTP Modified One-Generation study design GLP: FDA GLP","endpoint":"developmental toxicity","ingredient":", and this warrants further","loael_value":"","noael_unit":"ppm","noael_value":"3000","page":27,"route":"","species":"","study_id":"sccs_o_247_noael_006"}
UnifiedCodex:SCCS_SHADOW:beta.noael_studies	developmental toxicity	6	%	rat	oral	prenatal	developmental toxicity	SOURCE_SUBDIR=sccs_o_247; REPORT_TITLE=Final Opinion Scientific Committee on Consumer Safety SCCS OPINION on Benzophenone-3 (CAS No 131-57-7, EC No 205-031-5); OPINION_NUMBER=SCCS/1625/20; COMMITTEE=Scientific Committee on Consumer Safety (SCCS); REPORT_DATE=31 March 2021; VALUE_TEXT=6; DOSE=Details of the calculation of systemic exposure dose (SED) are presented in the Tables in Annex-2.; EFFECT=et al. (2015) study. Because of the evidence for rapid and almost complete absorption of BP-3 from the oral route, the SCCS has not applied any adjustment for bioavailability to this NOAEL value. Details of the calculation of systemic exposure dose (SED) are presented in the Tables in Annex-2. The calculation of MoS for different product types are given in Table 3 below: Table 3: Calculation of Margin of Safety for different products containing BP-3 Products Conc. Surface Systemic Exposure Dose (SED) mg/kg bw/d NOAEL* MOS Dermal Inhalation Oral Total UV cream 6% whole body 1.782 0 0 1.782 67.9 38 UV aerosolised spray 6% whole body 1.782 0.105 0 1.887 67.9 36 UV pump spray 6% whole body 1.782 0.001053 0 1.783 67.9 38 UV face cream 6% face 0.152 0 0 0.152 67.9 447 UV hand cream 6% hand 0.214 0 0 0.214 67.9 317 Non-UV** 0.50% whole body 0.116 0 0 0.116 67.9 585 Lipstick 6% lips 0.000 0 0.054 0.054 67.9 1257 * derived from prenatal and postnatal developmental study, oral, rat (Nakamura et al., 2015) ** to protect cosmetic formulat; CITATION_NUMBERS=[]; DETAILS_JSON={"cas_number":"131-57-7","citation":"","dose":"Details of the calculation of systemic exposure dose (SED) are presented in the Tables in Annex-2.","duration":"prenatal","effect":"et al. (2015) study. Because of the evidence for rapid and almost complete absorption of BP-3 from the oral route, the SCCS has not applied any adjustment for bioavailability to this NOAEL value. Details of the calculation of systemic exposure dose (SED) are presented in the Tables in Annex-2. The calculation of MoS for different product types are given in Table 3 below: Table 3: Calculation of Margin of Safety for different products containing BP-3 Products Conc. Surface Systemic Exposure Dose (SED) mg/kg bw/d NOAEL* MOS Dermal Inhalation Oral Total UV cream 6% whole body 1.782 0 0 1.782 67.9 38 UV aerosolised spray 6% whole body 1.782 0.105 0 1.887 67.9 36 UV pump spray 6% whole body 1.782 0.001053 0 1.783 67.9 38 UV face cream 6% face 0.152 0 0 0.152 67.9 447 UV hand cream 6% hand 0.214 0 0 0.214 67.9 317 Non-UV** 0.50% whole body 0.116 0 0 0.116 67.9 585 Lipstick 6% lips 0.000 0 0.054 0.054 67.9 1257 * derived from prenatal and postnatal developmental study, oral, rat (Nakamura et al., 2015) ** to protect cosmetic formulat","endpoint":"developmental toxicity","ingredient":", and this warrants further","loael_value":"","noael_unit":"%","noael_value":"6","page":47,"route":"oral","species":"rat","study_id":"sccs_o_247_noael_012"}
UnifiedCodex:SCCS_SHADOW:beta.noael_studies	developmental toxicity	1000	mg/kg bw/day	rat	oral	Prenatal	developmental toxicity	SOURCE_SUBDIR=sccs_o_247; REPORT_TITLE=Final Opinion Scientific Committee on Consumer Safety SCCS OPINION on Benzophenone-3 (CAS No 131-57-7, EC No 205-031-5); OPINION_NUMBER=SCCS/1625/20; COMMITTEE=Scientific Committee on Consumer Safety (SCCS); REPORT_DATE=31 March 2021; VALUE_TEXT=1000; DOSE=Summary of the available in vivo studies on reproduction function and ED effects of BP-3 Number and reference Species Strain Model Routes Dose, Exposure period Group size Outcomes reported NOAEL/ LOAEL derived by the authors SCCS Comments General toxicity Reprotoxicity Teratogenicity ED related effects - 1- Prenatal developmen tal tox study Stud...; EFFECT=SCCS/1625/20 Final Opinion Opinion on Benzophenone-3 (CAS No 131-57-7, EC No 205-031-5) _________________________________________________________________________________________________________________ 62 Annex - 1: Summary of the available in vivo studies on reproduction function and ED effects of BP-3 Number and reference Species Strain Model Routes Dose, Exposure period Group size Outcomes reported NOAEL/ LOAEL derived by the authors SCCS Comments General toxicity Reprotoxicity Teratogenicity ED related effects - 1- Prenatal developmen tal tox study Study period: 2004. Ref: 5, 33 in submission dossier OECD 414 GLP Rat Wistar CrI: WI (Han) Oral Gavage in corn oil 0, 40, 200 and 1000 mg/kg bw/day From GD5 to GD 19 observatio ns at GD 20 25 No adverse effects in the dams no significant difference in the number of implantation sites/litter, mean resorptions/litt er, % litters with resorptions, number and weights of; CITATION=Ref: 5, 33 in submission dossier OECD 414 GLP Rat Wistar CrI: WI (Han) Oral Gavage in corn oil 0, 40, 200 and 1000 mg/kg bw/day From GD5 to GD 19 observatio ns at GD 20 25 No adverse ef; CITATION_NUMBERS=[5,33,414,40,200,1000,19,20,25]; REFERENCE=Ref: 5, 33 in submission dossier OECD 414 GLP Rat Wistar CrI: WI (Han) Oral Gavage in corn oil 0, 40, 200 and 1000 mg/kg bw/day From GD5 to GD 19 observatio ns at GD 20 25 No adverse ef; DETAILS_JSON={"cas_number":"131-57-7","citation":"Ref: 5, 33 in submission dossier OECD 414 GLP Rat Wistar CrI: WI (Han) Oral Gavage in corn oil 0, 40, 200 and 1000 mg/kg bw/day From GD5 to GD 19 observatio ns at GD 20 25 No adverse ef","dose":"Summary of the available in vivo studies on reproduction function and ED effects of BP-3 Number and reference Species Strain Model Routes Dose, Exposure period Group size Outcomes reported NOAEL/ LOAEL derived by the authors SCCS Comments General toxicity Reprotoxicity Teratogenicity ED related effects - 1- Prenatal developmen tal tox study Stud...","duration":"Prenatal","effect":"SCCS/1625/20 Final Opinion Opinion on Benzophenone-3 (CAS No 131-57-7, EC No 205-031-5) _________________________________________________________________________________________________________________ 62 Annex - 1: Summary of the available in vivo studies on reproduction function and ED effects of BP-3 Number and reference Species Strain Model Routes Dose, Exposure period Group size Outcomes reported NOAEL/ LOAEL derived by the authors SCCS Comments General toxicity Reprotoxicity Teratogenicity ED related effects - 1- Prenatal developmen tal tox study Study period: 2004. Ref: 5, 33 in submission dossier OECD 414 GLP Rat Wistar CrI: WI (Han) Oral Gavage in corn oil 0, 40, 200 and 1000 mg/kg bw/day From GD5 to GD 19 observatio ns at GD 20 25 No adverse effects in the dams no significant difference in the number of implantation sites/litter, mean resorptions/litt er, % litters with resorptions, number and weights of","endpoint":"developmental toxicity","ingredient":", and this warrants further","loael_value":"","noael_unit":"mg/kg bw/day","noael_value":"1000","page":62,"route":"oral","species":"rat","study_id":"sccs_o_247_noael_018"}
UnifiedCodex:SCCS_SHADOW:beta.noael_studies	developmental toxicity	=200	mg/kg bw/d	rat	oral	-	developmental toxicity	SOURCE_SUBDIR=sccs_o_247; REPORT_TITLE=Final Opinion Scientific Committee on Consumer Safety SCCS OPINION on Benzophenone-3 (CAS No 131-57-7, EC No 205-031-5); OPINION_NUMBER=SCCS/1625/20; COMMITTEE=Scientific Committee on Consumer Safety (SCCS); REPORT_DATE=31 March 2021; VALUE_TEXT== 200; DOSE=WI (Han) Oral Gavage in corn oil 0, 40, 200 and 1000 mg/kg bw/day From GD5 to GD 19 observatio ns at GD 20 25 No adverse effects in the dams no significant difference in the number of implantation sites/litter, mean resorptions/litt er, % litters with resorptions, number and weights of live fetuses, between the control and treated groups No tera...; EFFECT=study Study period: 2004. Ref: 5, 33 in submission dossier OECD 414 GLP Rat Wistar CrI: WI (Han) Oral Gavage in corn oil 0, 40, 200 and 1000 mg/kg bw/day From GD5 to GD 19 observatio ns at GD 20 25 No adverse effects in the dams no significant difference in the number of implantation sites/litter, mean resorptions/litt er, % litters with resorptions, number and weights of live fetuses, between the control and treated groups No teratogenic effects Minor disturbance ad delay of ossification at 1000 mg/kg bw/day NOAEL mat. = 200 mg/kg bw/d NOAEL dev. = 200 mg/kg bw/d This study has been used in the previous SCCS opinion as the key study for calculation of the MOS. - 2 - Nakamura et al. 2015 Birth Defects Res 104: 35- 51 Study period: Rat Sprague- Dawley Food , 0, 1000, 3000, 10 000, 25 000, 50 000 ppm, i.e. around 67.9, 207.1, 670.8, 1798.3, 7-8 ↓ body weights of dams at 50 000 ppm at GD 10, 15 and 20; and at 25 000 ppm at GD15 ↓ organ (liver, kidney) weights (absolute no significant difference in the number of implantation si; CITATION=Ref: 5, 33 in submission dossier OECD 414 GLP Rat Wistar CrI: WI (Han) Oral Gavage in corn oil 0, 40, 200 and 1000 mg/kg bw/day From GD5 to GD 19 observatio ns at GD 20 25 No adverse ef; CITATION_NUMBERS=[5,33,414,40,200,1000,19,20,25]; REFERENCE=Ref: 5, 33 in submission dossier OECD 414 GLP Rat Wistar CrI: WI (Han) Oral Gavage in corn oil 0, 40, 200 and 1000 mg/kg bw/day From GD5 to GD 19 observatio ns at GD 20 25 No adverse ef; DETAILS_JSON={"cas_number":"131-57-7","citation":"Ref: 5, 33 in submission dossier OECD 414 GLP Rat Wistar CrI: WI (Han) Oral Gavage in corn oil 0, 40, 200 and 1000 mg/kg bw/day From GD5 to GD 19 observatio ns at GD 20 25 No adverse ef","dose":"WI (Han) Oral Gavage in corn oil 0, 40, 200 and 1000 mg/kg bw/day From GD5 to GD 19 observatio ns at GD 20 25 No adverse effects in the dams no significant difference in the number of implantation sites/litter, mean resorptions/litt er, % litters with resorptions, number and weights of live fetuses, between the control and treated groups No tera...","duration":"","effect":"study Study period: 2004. Ref: 5, 33 in submission dossier OECD 414 GLP Rat Wistar CrI: WI (Han) Oral Gavage in corn oil 0, 40, 200 and 1000 mg/kg bw/day From GD5 to GD 19 observatio ns at GD 20 25 No adverse effects in the dams no significant difference in the number of implantation sites/litter, mean resorptions/litt er, % litters with resorptions, number and weights of live fetuses, between the control and treated groups No teratogenic effects Minor disturbance ad delay of ossification at 1000 mg/kg bw/day NOAEL mat. = 200 mg/kg bw/d NOAEL dev. = 200 mg/kg bw/d This study has been used in the previous SCCS opinion as the key study for calculation of the MOS. - 2 - Nakamura et al. 2015 Birth Defects Res 104: 35- 51 Study period: Rat Sprague- Dawley Food , 0, 1000, 3000, 10 000, 25 000, 50 000 ppm, i.e. around 67.9, 207.1, 670.8, 1798.3, 7-8 ↓ body weights of dams at 50 000 ppm at GD 10, 15 and 20; and at 25 000 ppm at GD15 ↓ organ (liver, kidney) weights (absolute no significant difference in the number of implantation si","endpoint":"developmental toxicity","ingredient":", and this warrants further","loael_value":"","noael_unit":"mg/kg bw/d","noael_value":"= 200","page":62,"route":"oral","species":"rat","study_id":"sccs_o_247_noael_019"}
UnifiedCodex:SCCS_SHADOW:beta.noael_studies	developmental toxicity	=200	mg/kg bw/d	rat	oral	-	developmental toxicity	SOURCE_SUBDIR=sccs_o_247; REPORT_TITLE=Final Opinion Scientific Committee on Consumer Safety SCCS OPINION on Benzophenone-3 (CAS No 131-57-7, EC No 205-031-5); OPINION_NUMBER=SCCS/1625/20; COMMITTEE=Scientific Committee on Consumer Safety (SCCS); REPORT_DATE=31 March 2021; VALUE_TEXT== 200; DOSE=WI (Han) Oral Gavage in corn oil 0, 40, 200 and 1000 mg/kg bw/day From GD5 to GD 19 observatio ns at GD 20 25 No adverse effects in the dams no significant difference in the number of implantation sites/litter, mean resorptions/litt er, % litters with resorptions, number and weights of live fetuses, between the control and treated groups No tera...; EFFECT=Ref: 5, 33 in submission dossier OECD 414 GLP Rat Wistar CrI: WI (Han) Oral Gavage in corn oil 0, 40, 200 and 1000 mg/kg bw/day From GD5 to GD 19 observatio ns at GD 20 25 No adverse effects in the dams no significant difference in the number of implantation sites/litter, mean resorptions/litt er, % litters with resorptions, number and weights of live fetuses, between the control and treated groups No teratogenic effects Minor disturbance ad delay of ossification at 1000 mg/kg bw/day NOAEL mat. = 200 mg/kg bw/d NOAEL dev. = 200 mg/kg bw/d This study has been used in the previous SCCS opinion as the key study for calculation of the MOS. - 2 - Nakamura et al. 2015 Birth Defects Res 104: 35- 51 Study period: Rat Sprague- Dawley Food , 0, 1000, 3000, 10 000, 25 000, 50 000 ppm, i.e. around 67.9, 207.1, 670.8, 1798.3, 7-8 ↓ body weights of dams at 50 000 ppm at GD 10, 15 and 20; and at 25 000 ppm at GD15 ↓ organ (liver, kidney) weights (absolute no significant difference in the number of implantation sites/litter, mean resorptions; CITATION=Ref: 5, 33 in submission dossier OECD 414 GLP Rat Wistar CrI: WI (Han) Oral Gavage in corn oil 0, 40, 200 and 1000 mg/kg bw/day From GD5 to GD 19 observatio ns at GD 20 25 No adverse ef; CITATION_NUMBERS=[5,33,414,40,200,1000,19,20,25]; REFERENCE=Ref: 5, 33 in submission dossier OECD 414 GLP Rat Wistar CrI: WI (Han) Oral Gavage in corn oil 0, 40, 200 and 1000 mg/kg bw/day From GD5 to GD 19 observatio ns at GD 20 25 No adverse ef; DETAILS_JSON={"cas_number":"131-57-7","citation":"Ref: 5, 33 in submission dossier OECD 414 GLP Rat Wistar CrI: WI (Han) Oral Gavage in corn oil 0, 40, 200 and 1000 mg/kg bw/day From GD5 to GD 19 observatio ns at GD 20 25 No adverse ef","dose":"WI (Han) Oral Gavage in corn oil 0, 40, 200 and 1000 mg/kg bw/day From GD5 to GD 19 observatio ns at GD 20 25 No adverse effects in the dams no significant difference in the number of implantation sites/litter, mean resorptions/litt er, % litters with resorptions, number and weights of live fetuses, between the control and treated groups No tera...","duration":"","effect":"Ref: 5, 33 in submission dossier OECD 414 GLP Rat Wistar CrI: WI (Han) Oral Gavage in corn oil 0, 40, 200 and 1000 mg/kg bw/day From GD5 to GD 19 observatio ns at GD 20 25 No adverse effects in the dams no significant difference in the number of implantation sites/litter, mean resorptions/litt er, % litters with resorptions, number and weights of live fetuses, between the control and treated groups No teratogenic effects Minor disturbance ad delay of ossification at 1000 mg/kg bw/day NOAEL mat. = 200 mg/kg bw/d NOAEL dev. = 200 mg/kg bw/d This study has been used in the previous SCCS opinion as the key study for calculation of the MOS. - 2 - Nakamura et al. 2015 Birth Defects Res 104: 35- 51 Study period: Rat Sprague- Dawley Food , 0, 1000, 3000, 10 000, 25 000, 50 000 ppm, i.e. around 67.9, 207.1, 670.8, 1798.3, 7-8 ↓ body weights of dams at 50 000 ppm at GD 10, 15 and 20; and at 25 000 ppm at GD15 ↓ organ (liver, kidney) weights (absolute no significant difference in the number of implantation sites/litter, mean resorptions","endpoint":"developmental toxicity","ingredient":", and this warrants further","loael_value":"","noael_unit":"mg/kg bw/d","noael_value":"= 200","page":62,"route":"oral","species":"rat","study_id":"sccs_o_247_noael_020"}
UnifiedCodex:SCCS_SHADOW:beta.noael_studies	developmental toxicity	1000	ppm	rat	oral	-	developmental toxicity	SOURCE_SUBDIR=sccs_o_247; REPORT_TITLE=Final Opinion Scientific Committee on Consumer Safety SCCS OPINION on Benzophenone-3 (CAS No 131-57-7, EC No 205-031-5); OPINION_NUMBER=SCCS/1625/20; COMMITTEE=Scientific Committee on Consumer Safety (SCCS); REPORT_DATE=31 March 2021; VALUE_TEXT=1000; DOSE=aries and uterine weights (absolute and relative) at 1000 ppm but not at higher doses doses (dose related) ↑ apoptic cells in seminiferous tubules at 10 000 ppm and above (not dose related) Limited ↓ testo level at 3000 and 25 000 ppm In female offspring at PND23 Delayed follicular development at 10 000 and 50 000 ppm system (↓ AGD, ↓ spermatocy...; LOAEL_VALUE=68 mg /kg bw/day; EFFECT=aries and uterine weights (absolute and relative) at 1000 ppm but not at higher doses doses (dose related) ↑ apoptic cells in seminiferous tubules at 10 000 ppm and above (not dose related) Limited ↓ testo level at 3000 and 25 000 ppm In female offspring at PND23 Delayed follicular development at 10 000 and 50 000 ppm system (↓ AGD, ↓ spermatocytes production and/or quality…) Due to the effects on the ↓ of spermatocyte which may be due to an ED effects of BP-3 SCCS considered 3000 ppm as a LOAEL and therefore the NOAEL should be 1000 ppm ( 68 mg /kg bw/day) - 3 - Submission Ref 11 Study period: 2012 (final report in 2015) Equivalent to OECD 414 GLP Rat Sprague- Dawley Oral Food 0, 3000, 10 000 and 30 000, ppm, i.e. around 242, 725 and 3689 mg/kg/ bw/day From GD 5 to GD 15 Observatio n at GD 15 25 .↓ body weights at 10 000 and 30 000 ppm and ↑ food consumption at 30 000 ppm modifications of blood biochemical factors at 30 000 ppm No effects on foetuses, litters No teratogenic effects observed excepted increased skeletal variatio; CITATION_NUMBERS=[]; DETAILS_JSON={"cas_number":"131-57-7","citation":"","dose":"aries and uterine weights (absolute and relative) at 1000 ppm but not at higher doses doses (dose related) ↑ apoptic cells in seminiferous tubules at 10 000 ppm and above (not dose related) Limited ↓ testo level at 3000 and 25 000 ppm In female offspring at PND23 Delayed follicular development at 10 000 and 50 000 ppm system (↓ AGD, ↓ spermatocy...","duration":"","effect":"aries and uterine weights (absolute and relative) at 1000 ppm but not at higher doses doses (dose related) ↑ apoptic cells in seminiferous tubules at 10 000 ppm and above (not dose related) Limited ↓ testo level at 3000 and 25 000 ppm In female offspring at PND23 Delayed follicular development at 10 000 and 50 000 ppm system (↓ AGD, ↓ spermatocytes production and/or quality…) Due to the effects on the ↓ of spermatocyte which may be due to an ED effects of BP-3 SCCS considered 3000 ppm as a LOAEL and therefore the NOAEL should be 1000 ppm ( 68 mg /kg bw/day) - 3 - Submission Ref 11 Study period: 2012 (final report in 2015) Equivalent to OECD 414 GLP Rat Sprague- Dawley Oral Food 0, 3000, 10 000 and 30 000, ppm, i.e. around 242, 725 and 3689 mg/kg/ bw/day From GD 5 to GD 15 Observatio n at GD 15 25 .↓ body weights at 10 000 and 30 000 ppm and ↑ food consumption at 30 000 ppm modifications of blood biochemical factors at 30 000 ppm No effects on foetuses, litters No teratogenic effects observed excepted increased skeletal variatio","endpoint":"developmental toxicity","ingredient":", and this warrants further","loael_value":"68 mg /kg bw/day","noael_unit":"ppm","noael_value":"1000","page":63,"route":"oral","species":"rat","study_id":"sccs_o_247_noael_022"}
UnifiedCodex:SCCS_SHADOW:beta.noael_studies	developmental toxicity	=242	mg/kg bw/d	rat	oral	-	developmental toxicity	SOURCE_SUBDIR=sccs_o_247; REPORT_TITLE=Final Opinion Scientific Committee on Consumer Safety SCCS OPINION on Benzophenone-3 (CAS No 131-57-7, EC No 205-031-5); OPINION_NUMBER=SCCS/1625/20; COMMITTEE=Scientific Committee on Consumer Safety (SCCS); REPORT_DATE=31 March 2021; VALUE_TEXT== 242; DOSE=2012 (final report in 2015) Equivalent to OECD 414 GLP Rat Sprague- Dawley Oral Food 0, 3000, 10 000 and 30 000, ppm, i.e. around 242, 725 and 3689 mg/kg/ bw/day From GD 5 to GD 15 Observatio n at GD 15 25 .↓ body weights at 10 000 and 30 000 ppm and ↑ food consumption at 30 000 ppm modifications of blood biochemical factors at 30 000 ppm No eff...; EFFECT=SCCS-rejected applicant NOAEL: y) - 3 - Submission Ref 11 Study period: 2012 (final report in 2015) Equivalent to OECD 414 GLP Rat Sprague- Dawley Oral Food 0, 3000, 10 000 and 30 000, ppm, i.e. around 242, 725 and 3689 mg/kg/ bw/day From GD 5 to GD 15 Observatio n at GD 15 25 .↓ body weights at 10 000 and 30 000 ppm and ↑ food consumption at 30 000 ppm modifications of blood biochemical factors at 30 000 ppm No effects on foetuses, litters No teratogenic effects observed excepted increased skeletal variations not considered treatment related NOAEL mat. = 242 mg/kg bw/d NOAEL dev. = 3689 mg/kg bw/d SCCS agrees with the authors conclusion.; CITATION_NUMBERS=[]; DETAILS_JSON={"cas_number":"131-57-7","citation":"","dose":"2012 (final report in 2015) Equivalent to OECD 414 GLP Rat Sprague- Dawley Oral Food 0, 3000, 10 000 and 30 000, ppm, i.e. around 242, 725 and 3689 mg/kg/ bw/day From GD 5 to GD 15 Observatio n at GD 15 25 .↓ body weights at 10 000 and 30 000 ppm and ↑ food consumption at 30 000 ppm modifications of blood biochemical factors at 30 000 ppm No eff...","duration":"","effect":"SCCS-rejected applicant NOAEL: y) - 3 - Submission Ref 11 Study period: 2012 (final report in 2015) Equivalent to OECD 414 GLP Rat Sprague- Dawley Oral Food 0, 3000, 10 000 and 30 000, ppm, i.e. around 242, 725 and 3689 mg/kg/ bw/day From GD 5 to GD 15 Observatio n at GD 15 25 .↓ body weights at 10 000 and 30 000 ppm and ↑ food consumption at 30 000 ppm modifications of blood biochemical factors at 30 000 ppm No effects on foetuses, litters No teratogenic effects observed excepted increased skeletal variations not considered treatment related NOAEL mat. = 242 mg/kg bw/d NOAEL dev. = 3689 mg/kg bw/d SCCS agrees with the authors conclusion.","endpoint":"developmental toxicity","ingredient":", and this warrants further","loael_value":"","noael_unit":"mg/kg bw/d","noael_value":"= 242","page":63,"route":"oral","species":"rat","study_id":"sccs_o_247_noael_023"}
UnifiedCodex:SCCS_SHADOW:beta.noael_studies	developmental toxicity	=242	mg/kg bw/d	rat	oral	-	developmental toxicity	SOURCE_SUBDIR=sccs_o_247; REPORT_TITLE=Final Opinion Scientific Committee on Consumer Safety SCCS OPINION on Benzophenone-3 (CAS No 131-57-7, EC No 205-031-5); OPINION_NUMBER=SCCS/1625/20; COMMITTEE=Scientific Committee on Consumer Safety (SCCS); REPORT_DATE=31 March 2021; VALUE_TEXT== 242; DOSE=2012 (final report in 2015) Equivalent to OECD 414 GLP Rat Sprague- Dawley Oral Food 0, 3000, 10 000 and 30 000, ppm, i.e. around 242, 725 and 3689 mg/kg/ bw/day From GD 5 to GD 15 Observatio n at GD 15 25 .↓ body weights at 10 000 and 30 000 ppm and ↑ food consumption at 30 000 ppm modifications of blood biochemical factors at 30 000 ppm No eff...; EFFECT=SCCS-rejected applicant NOAEL: tudy period: 2012 (final report in 2015) Equivalent to OECD 414 GLP Rat Sprague- Dawley Oral Food 0, 3000, 10 000 and 30 000, ppm, i.e. around 242, 725 and 3689 mg/kg/ bw/day From GD 5 to GD 15 Observatio n at GD 15 25 .↓ body weights at 10 000 and 30 000 ppm and ↑ food consumption at 30 000 ppm modifications of blood biochemical factors at 30 000 ppm No effects on foetuses, litters No teratogenic effects observed excepted increased skeletal variations not considered treatment related NOAEL mat. = 242 mg/kg bw/d NOAEL dev. = 3689 mg/kg bw/d SCCS agrees with the authors conclusion.; CITATION_NUMBERS=[]; DETAILS_JSON={"cas_number":"131-57-7","citation":"","dose":"2012 (final report in 2015) Equivalent to OECD 414 GLP Rat Sprague- Dawley Oral Food 0, 3000, 10 000 and 30 000, ppm, i.e. around 242, 725 and 3689 mg/kg/ bw/day From GD 5 to GD 15 Observatio n at GD 15 25 .↓ body weights at 10 000 and 30 000 ppm and ↑ food consumption at 30 000 ppm modifications of blood biochemical factors at 30 000 ppm No eff...","duration":"","effect":"SCCS-rejected applicant NOAEL: tudy period: 2012 (final report in 2015) Equivalent to OECD 414 GLP Rat Sprague- Dawley Oral Food 0, 3000, 10 000 and 30 000, ppm, i.e. around 242, 725 and 3689 mg/kg/ bw/day From GD 5 to GD 15 Observatio n at GD 15 25 .↓ body weights at 10 000 and 30 000 ppm and ↑ food consumption at 30 000 ppm modifications of blood biochemical factors at 30 000 ppm No effects on foetuses, litters No teratogenic effects observed excepted increased skeletal variations not considered treatment related NOAEL mat. = 242 mg/kg bw/d NOAEL dev. = 3689 mg/kg bw/d SCCS agrees with the authors conclusion.","endpoint":"developmental toxicity","ingredient":", and this warrants further","loael_value":"","noael_unit":"mg/kg bw/d","noael_value":"= 242","page":63,"route":"oral","species":"rat","study_id":"sccs_o_247_noael_024"}
UnifiedCodex:SCCS_SHADOW:beta.noael_studies	developmental toxicity	=200	mg/kg bw/d	mouse	oral	2 years	developmental toxicity	SOURCE_SUBDIR=sccs_o_247; REPORT_TITLE=Final Opinion Scientific Committee on Consumer Safety SCCS OPINION on Benzophenone-3 (CAS No 131-57-7, EC No 205-031-5); OPINION_NUMBER=SCCS/1625/20; COMMITTEE=Scientific Committee on Consumer Safety (SCCS); REPORT_DATE=31 March 2021; VALUE_TEXT== 200; DOSE=d f at 10 000 ppm over the course of the study and at 3000 ppm in f at week 77 No effects on number of pups, litter size, sex distribution, In female F1: ↑ stromal polyp and endometrium hyperplasia ppm in the uterus at 3000 In male F1: ↑ fibirnoid necrosis of the arterioles at 10 000 ppm at the end of the 2 years No teratogenic effects except at...; EFFECT=d f at 10 000 ppm over the course of the study and at 3000 ppm in f at week 77 No effects on number of pups, litter size, sex distribution, In female F1: ↑ stromal polyp and endometrium hyperplasia ppm in the uterus at 3000 In male F1: ↑ fibirnoid necrosis of the arterioles at 10 000 ppm at the end of the 2 years No teratogenic effects except at the highest dose: skeletal aberrations in the presence of maternal toxicity ↑ incidence of C-cell adenoma in the thyroid gland at 3000 ppm in f at the end of the 2 years NOAEL mat. = 200 mg/kg bw/d NOAEL dev. = 200 mg/kg bw/d The SCCS agrees with the derived NOAEL values. - 5 - Ref 21 in submission dossier Mouse B6C3F1/N Oral Food 0, 1000, 3000, and 10000, ppm, i.e. around 50 m and 50 f per dose ↓ body weights of F1 m and f at 10 000 ppm over the; CITATION_NUMBERS=[]; DETAILS_JSON={"cas_number":"131-57-7","citation":"","dose":"d f at 10 000 ppm over the course of the study and at 3000 ppm in f at week 77 No effects on number of pups, litter size, sex distribution, In female F1: ↑ stromal polyp and endometrium hyperplasia ppm in the uterus at 3000 In male F1: ↑ fibirnoid necrosis of the arterioles at 10 000 ppm at the end of the 2 years No teratogenic effects except at...","duration":"2 years","effect":"d f at 10 000 ppm over the course of the study and at 3000 ppm in f at week 77 No effects on number of pups, litter size, sex distribution, In female F1: ↑ stromal polyp and endometrium hyperplasia ppm in the uterus at 3000 In male F1: ↑ fibirnoid necrosis of the arterioles at 10 000 ppm at the end of the 2 years No teratogenic effects except at the highest dose: skeletal aberrations in the presence of maternal toxicity ↑ incidence of C-cell adenoma in the thyroid gland at 3000 ppm in f at the end of the 2 years NOAEL mat. = 200 mg/kg bw/d NOAEL dev. = 200 mg/kg bw/d The SCCS agrees with the derived NOAEL values. - 5 - Ref 21 in submission dossier Mouse B6C3F1/N Oral Food 0, 1000, 3000, and 10000, ppm, i.e. around 50 m and 50 f per dose ↓ body weights of F1 m and f at 10 000 ppm over the","endpoint":"developmental toxicity","ingredient":", and this warrants further","loael_value":"","noael_unit":"mg/kg bw/d","noael_value":"= 200","page":64,"route":"oral","species":"mouse","study_id":"sccs_o_247_noael_025"}
UnifiedCodex:SCCS_SHADOW:beta.noael_studies	developmental toxicity	=200	mg/kg bw/d	mouse	oral	2 years	developmental toxicity	SOURCE_SUBDIR=sccs_o_247; REPORT_TITLE=Final Opinion Scientific Committee on Consumer Safety SCCS OPINION on Benzophenone-3 (CAS No 131-57-7, EC No 205-031-5); OPINION_NUMBER=SCCS/1625/20; COMMITTEE=Scientific Committee on Consumer Safety (SCCS); REPORT_DATE=31 March 2021; VALUE_TEXT== 200; DOSE=ourse of the study and at 3000 ppm in f at week 77 No effects on number of pups, litter size, sex distribution, In female F1: ↑ stromal polyp and endometrium hyperplasia ppm in the uterus at 3000 In male F1: ↑ fibirnoid necrosis of the arterioles at 10 000 ppm at the end of the 2 years No teratogenic effects except at the highest dose: skeletal...; EFFECT=ourse of the study and at 3000 ppm in f at week 77 No effects on number of pups, litter size, sex distribution, In female F1: ↑ stromal polyp and endometrium hyperplasia ppm in the uterus at 3000 In male F1: ↑ fibirnoid necrosis of the arterioles at 10 000 ppm at the end of the 2 years No teratogenic effects except at the highest dose: skeletal aberrations in the presence of maternal toxicity ↑ incidence of C-cell adenoma in the thyroid gland at 3000 ppm in f at the end of the 2 years NOAEL mat. = 200 mg/kg bw/d NOAEL dev. = 200 mg/kg bw/d The SCCS agrees with the derived NOAEL values. - 5 - Ref 21 in submission dossier Mouse B6C3F1/N Oral Food 0, 1000, 3000, and 10000, ppm, i.e. around 50 m and 50 f per dose ↓ body weights of F1 m and f at 10 000 ppm over the; CITATION_NUMBERS=[]; DETAILS_JSON={"cas_number":"131-57-7","citation":"","dose":"ourse of the study and at 3000 ppm in f at week 77 No effects on number of pups, litter size, sex distribution, In female F1: ↑ stromal polyp and endometrium hyperplasia ppm in the uterus at 3000 In male F1: ↑ fibirnoid necrosis of the arterioles at 10 000 ppm at the end of the 2 years No teratogenic effects except at the highest dose: skeletal...","duration":"2 years","effect":"ourse of the study and at 3000 ppm in f at week 77 No effects on number of pups, litter size, sex distribution, In female F1: ↑ stromal polyp and endometrium hyperplasia ppm in the uterus at 3000 In male F1: ↑ fibirnoid necrosis of the arterioles at 10 000 ppm at the end of the 2 years No teratogenic effects except at the highest dose: skeletal aberrations in the presence of maternal toxicity ↑ incidence of C-cell adenoma in the thyroid gland at 3000 ppm in f at the end of the 2 years NOAEL mat. = 200 mg/kg bw/d NOAEL dev. = 200 mg/kg bw/d The SCCS agrees with the derived NOAEL values. - 5 - Ref 21 in submission dossier Mouse B6C3F1/N Oral Food 0, 1000, 3000, and 10000, ppm, i.e. around 50 m and 50 f per dose ↓ body weights of F1 m and f at 10 000 ppm over the","endpoint":"developmental toxicity","ingredient":", and this warrants further","loael_value":"","noael_unit":"mg/kg bw/d","noael_value":"= 200","page":64,"route":"oral","species":"mouse","study_id":"sccs_o_247_noael_026"}
UnifiedCodex:SCCS_SHADOW:beta.noael_studies	developmental toxicity	=200	mg/kg bw/d	mouse	oral	2 years	developmental toxicity	SOURCE_SUBDIR=sccs_o_247; REPORT_TITLE=Final Opinion Scientific Committee on Consumer Safety SCCS OPINION on Benzophenone-3 (CAS No 131-57-7, EC No 205-031-5); OPINION_NUMBER=SCCS/1625/20; COMMITTEE=Scientific Committee on Consumer Safety (SCCS); REPORT_DATE=31 March 2021; VALUE_TEXT== 200; DOSE=s on number of pups, litter size, sex distribution, In female F1: ↑ stromal polyp and endometrium hyperplasia ppm in the uterus at 3000 In male F1: ↑ fibirnoid necrosis of the arterioles at 10 000 ppm at the end of the 2 years No teratogenic effects except at the highest dose: skeletal aberrations in the presence of maternal toxicity ↑ incidence...; EFFECT=s on number of pups, litter size, sex distribution, In female F1: ↑ stromal polyp and endometrium hyperplasia ppm in the uterus at 3000 In male F1: ↑ fibirnoid necrosis of the arterioles at 10 000 ppm at the end of the 2 years No teratogenic effects except at the highest dose: skeletal aberrations in the presence of maternal toxicity ↑ incidence of C-cell adenoma in the thyroid gland at 3000 ppm in f at the end of the 2 years NOAEL mat. = 200 mg/kg bw/d NOAEL dev. = 200 mg/kg bw/d The SCCS agrees with the derived NOAEL values. - 5 - Ref 21 in submission dossier Mouse B6C3F1/N Oral Food 0, 1000, 3000, and 10000, ppm, i.e. around 50 m and 50 f per dose ↓ body weights of F1 m and f at 10 000 ppm over the; CITATION_NUMBERS=[]; DETAILS_JSON={"cas_number":"131-57-7","citation":"","dose":"s on number of pups, litter size, sex distribution, In female F1: ↑ stromal polyp and endometrium hyperplasia ppm in the uterus at 3000 In male F1: ↑ fibirnoid necrosis of the arterioles at 10 000 ppm at the end of the 2 years No teratogenic effects except at the highest dose: skeletal aberrations in the presence of maternal toxicity ↑ incidence...","duration":"2 years","effect":"s on number of pups, litter size, sex distribution, In female F1: ↑ stromal polyp and endometrium hyperplasia ppm in the uterus at 3000 In male F1: ↑ fibirnoid necrosis of the arterioles at 10 000 ppm at the end of the 2 years No teratogenic effects except at the highest dose: skeletal aberrations in the presence of maternal toxicity ↑ incidence of C-cell adenoma in the thyroid gland at 3000 ppm in f at the end of the 2 years NOAEL mat. = 200 mg/kg bw/d NOAEL dev. = 200 mg/kg bw/d The SCCS agrees with the derived NOAEL values. - 5 - Ref 21 in submission dossier Mouse B6C3F1/N Oral Food 0, 1000, 3000, and 10000, ppm, i.e. around 50 m and 50 f per dose ↓ body weights of F1 m and f at 10 000 ppm over the","endpoint":"developmental toxicity","ingredient":", and this warrants further","loael_value":"","noael_unit":"mg/kg bw/d","noael_value":"= 200","page":64,"route":"oral","species":"mouse","study_id":"sccs_o_247_noael_027"}
UnifiedCodex:SCCS_SHADOW:beta.noael_studies	developmental toxicity	1000	mg/kg bw/day	rat	oral	Prenatal	developmental toxicity	SOURCE_SUBDIR=sccs_o_247; REPORT_TITLE=Final Opinion Scientific Committee on Consumer Safety SCCS OPINION on Benzophenone-3 (CAS No 131-57-7, EC No 205-031-5); OPINION_NUMBER=SCCS/1625/20; COMMITTEE=Scientific Committee on Consumer Safety (SCCS); REPORT_DATE=31 March 2021; VALUE_TEXT=1000; DOSE=WI (Han) | Oral Gavage in corn oil | 0, 40, 200 and 1000 mg/kg bw/day From GD5 to GD 19 observatio ns at GD 20 | 25 | No adverse effects in the dams | no significant difference in the number of implantation sites/litter, mean resorptions/litt er, % litters with resorptions, number and weights of live fetuses, between the control and treated grou...; EFFECT=Unlabeled table on page 62: - 1- Prenatal developmen tal tox study Study period: 2004. Ref: 5, 33 in submission dossier OECD 414 GLP | Rat Wistar CrI: WI (Han) | Oral Gavage in corn oil | 0, 40, 200 and 1000 mg/kg bw/day From GD5 to GD 19 observatio ns at GD 20 | 25 | No adverse effects in the dams | no significant difference in the number of implantation sites/litter, mean resorptions/litt er, % litters with resorptions, number and weights of live fetuses, between the control and treated groups | No teratogenic effects Minor disturbance ad delay of ossification at 1000 mg/kg bw/day | NOAEL mat. = 200 mg/kg bw/d NOAEL dev. = 200 mg/kg bw/d | This study has been used in the previous SCCS opinion as the key study for calculation of the MOS.; CITATION=Ref: 5, 33 in submission dossier OECD 414 GLP | Rat Wistar CrI: WI (Han) | Oral Gavage in corn oil | 0, 40, 200 and 1000 mg/kg bw/day From GD5 to GD 19 observatio ns at GD 20 | 25 | No; CITATION_NUMBERS=[5,33,414,40,200,1000,19,20,25]; REFERENCE=Ref: 5, 33 in submission dossier OECD 414 GLP | Rat Wistar CrI: WI (Han) | Oral Gavage in corn oil | 0, 40, 200 and 1000 mg/kg bw/day From GD5 to GD 19 observatio ns at GD 20 | 25 | No; DETAILS_JSON={"cas_number":"131-57-7","citation":"Ref: 5, 33 in submission dossier OECD 414 GLP | Rat Wistar CrI: WI (Han) | Oral Gavage in corn oil | 0, 40, 200 and 1000 mg/kg bw/day From GD5 to GD 19 observatio ns at GD 20 | 25 | No","dose":"WI (Han) | Oral Gavage in corn oil | 0, 40, 200 and 1000 mg/kg bw/day From GD5 to GD 19 observatio ns at GD 20 | 25 | No adverse effects in the dams | no significant difference in the number of implantation sites/litter, mean resorptions/litt er, % litters with resorptions, number and weights of live fetuses, between the control and treated grou...","duration":"Prenatal","effect":"Unlabeled table on page 62: - 1- Prenatal developmen tal tox study Study period: 2004. Ref: 5, 33 in submission dossier OECD 414 GLP | Rat Wistar CrI: WI (Han) | Oral Gavage in corn oil | 0, 40, 200 and 1000 mg/kg bw/day From GD5 to GD 19 observatio ns at GD 20 | 25 | No adverse effects in the dams | no significant difference in the number of implantation sites/litter, mean resorptions/litt er, % litters with resorptions, number and weights of live fetuses, between the control and treated groups | No teratogenic effects Minor disturbance ad delay of ossification at 1000 mg/kg bw/day | NOAEL mat. = 200 mg/kg bw/d NOAEL dev. = 200 mg/kg bw/d | This study has been used in the previous SCCS opinion as the key study for calculation of the MOS.","endpoint":"developmental toxicity","ingredient":", and this warrants further","loael_value":"","noael_unit":"mg/kg bw/day","noael_value":"1000","page":62,"route":"oral","species":"rat","study_id":"sccs_o_247_noael_042"}
UnifiedCodex:SCCS_SHADOW:beta.noael_studies	developmental toxicity	=200	mg/kg bw/d	rat	oral	Prenatal	developmental toxicity	SOURCE_SUBDIR=sccs_o_247; REPORT_TITLE=Final Opinion Scientific Committee on Consumer Safety SCCS OPINION on Benzophenone-3 (CAS No 131-57-7, EC No 205-031-5); OPINION_NUMBER=SCCS/1625/20; COMMITTEE=Scientific Committee on Consumer Safety (SCCS); REPORT_DATE=31 March 2021; VALUE_TEXT== 200; DOSE=WI (Han) | Oral Gavage in corn oil | 0, 40, 200 and 1000 mg/kg bw/day From GD5 to GD 19 observatio ns at GD 20 | 25 | No adverse effects in the dams | no significant difference in the number of implantation sites/litter, mean resorptions/litt er, % litters with resorptions, number and weights of live fetuses, between the control and treated grou...; EFFECT=Unlabeled table on page 62: - 1- Prenatal developmen tal tox study Study period: 2004. Ref: 5, 33 in submission dossier OECD 414 GLP | Rat Wistar CrI: WI (Han) | Oral Gavage in corn oil | 0, 40, 200 and 1000 mg/kg bw/day From GD5 to GD 19 observatio ns at GD 20 | 25 | No adverse effects in the dams | no significant difference in the number of implantation sites/litter, mean resorptions/litt er, % litters with resorptions, number and weights of live fetuses, between the control and treated groups | No teratogenic effects Minor disturbance ad delay of ossification at 1000 mg/kg bw/day | NOAEL mat. = 200 mg/kg bw/d NOAEL dev. = 200 mg/kg bw/d | This study has been used in the previous SCCS opinion as the key study for calculation of the MOS.; CITATION=Ref: 5, 33 in submission dossier OECD 414 GLP | Rat Wistar CrI: WI (Han) | Oral Gavage in corn oil | 0, 40, 200 and 1000 mg/kg bw/day From GD5 to GD 19 observatio ns at GD 20 | 25 | No; CITATION_NUMBERS=[5,33,414,40,200,1000,19,20,25]; REFERENCE=Ref: 5, 33 in submission dossier OECD 414 GLP | Rat Wistar CrI: WI (Han) | Oral Gavage in corn oil | 0, 40, 200 and 1000 mg/kg bw/day From GD5 to GD 19 observatio ns at GD 20 | 25 | No; DETAILS_JSON={"cas_number":"131-57-7","citation":"Ref: 5, 33 in submission dossier OECD 414 GLP | Rat Wistar CrI: WI (Han) | Oral Gavage in corn oil | 0, 40, 200 and 1000 mg/kg bw/day From GD5 to GD 19 observatio ns at GD 20 | 25 | No","dose":"WI (Han) | Oral Gavage in corn oil | 0, 40, 200 and 1000 mg/kg bw/day From GD5 to GD 19 observatio ns at GD 20 | 25 | No adverse effects in the dams | no significant difference in the number of implantation sites/litter, mean resorptions/litt er, % litters with resorptions, number and weights of live fetuses, between the control and treated grou...","duration":"Prenatal","effect":"Unlabeled table on page 62: - 1- Prenatal developmen tal tox study Study period: 2004. Ref: 5, 33 in submission dossier OECD 414 GLP | Rat Wistar CrI: WI (Han) | Oral Gavage in corn oil | 0, 40, 200 and 1000 mg/kg bw/day From GD5 to GD 19 observatio ns at GD 20 | 25 | No adverse effects in the dams | no significant difference in the number of implantation sites/litter, mean resorptions/litt er, % litters with resorptions, number and weights of live fetuses, between the control and treated groups | No teratogenic effects Minor disturbance ad delay of ossification at 1000 mg/kg bw/day | NOAEL mat. = 200 mg/kg bw/d NOAEL dev. = 200 mg/kg bw/d | This study has been used in the previous SCCS opinion as the key study for calculation of the MOS.","endpoint":"developmental toxicity","ingredient":", and this warrants further","loael_value":"","noael_unit":"mg/kg bw/d","noael_value":"= 200","page":62,"route":"oral","species":"rat","study_id":"sccs_o_247_noael_044"}
UnifiedCodex:SCCS_SHADOW:beta.noael_studies	developmental toxicity	3689	mg/kg	rat	oral	-	developmental toxicity	SOURCE_SUBDIR=sccs_o_247; REPORT_TITLE=Final Opinion Scientific Committee on Consumer Safety SCCS OPINION on Benzophenone-3 (CAS No 131-57-7, EC No 205-031-5); OPINION_NUMBER=SCCS/1625/20; COMMITTEE=Scientific Committee on Consumer Safety (SCCS); REPORT_DATE=31 March 2021; VALUE_TEXT=3689; DOSE=2012 (final report in 2015) Equivalent to OECD 414 GLP | Rat Sprague- Dawley | Oral Food | 0, 3000, 10 000 and 30 000, ppm, i.e. around 242, 725 and 3689 mg/kg/ bw/day From GD 5 to GD 15 Observatio n at GD 15 | 25 | .↓ body weights at 10 000 and 30 000 ppm and ↑ food consumption at 30 000 ppm modifications of blood biochemical factors at 30 000...; EFFECT=SCCS-rejected applicant NOAEL: Unlabeled table on page 63: - 3 - Submission Ref 11 Study period: 2012 (final report in 2015) Equivalent to OECD 414 GLP | Rat Sprague- Dawley | Oral Food | 0, 3000, 10 000 and 30 000, ppm, i.e. around 242, 725 and 3689 mg/kg/ bw/day From GD 5 to GD 15 Observatio n at GD 15 | 25 | .↓ body weights at 10 000 and 30 000 ppm and ↑ food consumption at 30 000 ppm modifications of blood biochemical factors at 30 000 ppm | No effects on foetuses, litters | No teratogenic effects observed excepted increased skeletal variations not considered treatment related | NOAEL mat. = 242 mg/kg bw/d NOAEL dev. = 3689 mg/kg bw/d | SCCS agrees with the authors conclusion.; CITATION_NUMBERS=[]; DETAILS_JSON={"cas_number":"131-57-7","citation":"","dose":"2012 (final report in 2015) Equivalent to OECD 414 GLP | Rat Sprague- Dawley | Oral Food | 0, 3000, 10 000 and 30 000, ppm, i.e. around 242, 725 and 3689 mg/kg/ bw/day From GD 5 to GD 15 Observatio n at GD 15 | 25 | .↓ body weights at 10 000 and 30 000 ppm and ↑ food consumption at 30 000 ppm modifications of blood biochemical factors at 30 000...","duration":"","effect":"SCCS-rejected applicant NOAEL: Unlabeled table on page 63: - 3 - Submission Ref 11 Study period: 2012 (final report in 2015) Equivalent to OECD 414 GLP | Rat Sprague- Dawley | Oral Food | 0, 3000, 10 000 and 30 000, ppm, i.e. around 242, 725 and 3689 mg/kg/ bw/day From GD 5 to GD 15 Observatio n at GD 15 | 25 | .↓ body weights at 10 000 and 30 000 ppm and ↑ food consumption at 30 000 ppm modifications of blood biochemical factors at 30 000 ppm | No effects on foetuses, litters | No teratogenic effects observed excepted increased skeletal variations not considered treatment related | NOAEL mat. = 242 mg/kg bw/d NOAEL dev. = 3689 mg/kg bw/d | SCCS agrees with the authors conclusion.","endpoint":"developmental toxicity","ingredient":", and this warrants further","loael_value":"","noael_unit":"mg/kg","noael_value":"3689","page":63,"route":"oral","species":"rat","study_id":"sccs_o_247_noael_046"}
UnifiedCodex:SCCS_SHADOW:beta.noael_studies	developmental toxicity	=242	mg/kg bw/d	rat	oral	-	developmental toxicity	SOURCE_SUBDIR=sccs_o_247; REPORT_TITLE=Final Opinion Scientific Committee on Consumer Safety SCCS OPINION on Benzophenone-3 (CAS No 131-57-7, EC No 205-031-5); OPINION_NUMBER=SCCS/1625/20; COMMITTEE=Scientific Committee on Consumer Safety (SCCS); REPORT_DATE=31 March 2021; VALUE_TEXT== 242; DOSE=2012 (final report in 2015) Equivalent to OECD 414 GLP | Rat Sprague- Dawley | Oral Food | 0, 3000, 10 000 and 30 000, ppm, i.e. around 242, 725 and 3689 mg/kg/ bw/day From GD 5 to GD 15 Observatio n at GD 15 | 25 | .↓ body weights at 10 000 and 30 000 ppm and ↑ food consumption at 30 000 ppm modifications of blood biochemical factors at 30 000...; EFFECT=SCCS-rejected applicant NOAEL: Unlabeled table on page 63: - 3 - Submission Ref 11 Study period: 2012 (final report in 2015) Equivalent to OECD 414 GLP | Rat Sprague- Dawley | Oral Food | 0, 3000, 10 000 and 30 000, ppm, i.e. around 242, 725 and 3689 mg/kg/ bw/day From GD 5 to GD 15 Observatio n at GD 15 | 25 | .↓ body weights at 10 000 and 30 000 ppm and ↑ food consumption at 30 000 ppm modifications of blood biochemical factors at 30 000 ppm | No effects on foetuses, litters | No teratogenic effects observed excepted increased skeletal variations not considered treatment related | NOAEL mat. = 242 mg/kg bw/d NOAEL dev. = 3689 mg/kg bw/d | SCCS agrees with the authors conclusion.; CITATION_NUMBERS=[]; DETAILS_JSON={"cas_number":"131-57-7","citation":"","dose":"2012 (final report in 2015) Equivalent to OECD 414 GLP | Rat Sprague- Dawley | Oral Food | 0, 3000, 10 000 and 30 000, ppm, i.e. around 242, 725 and 3689 mg/kg/ bw/day From GD 5 to GD 15 Observatio n at GD 15 | 25 | .↓ body weights at 10 000 and 30 000 ppm and ↑ food consumption at 30 000 ppm modifications of blood biochemical factors at 30 000...","duration":"","effect":"SCCS-rejected applicant NOAEL: Unlabeled table on page 63: - 3 - Submission Ref 11 Study period: 2012 (final report in 2015) Equivalent to OECD 414 GLP | Rat Sprague- Dawley | Oral Food | 0, 3000, 10 000 and 30 000, ppm, i.e. around 242, 725 and 3689 mg/kg/ bw/day From GD 5 to GD 15 Observatio n at GD 15 | 25 | .↓ body weights at 10 000 and 30 000 ppm and ↑ food consumption at 30 000 ppm modifications of blood biochemical factors at 30 000 ppm | No effects on foetuses, litters | No teratogenic effects observed excepted increased skeletal variations not considered treatment related | NOAEL mat. = 242 mg/kg bw/d NOAEL dev. = 3689 mg/kg bw/d | SCCS agrees with the authors conclusion.","endpoint":"developmental toxicity","ingredient":", and this warrants further","loael_value":"","noael_unit":"mg/kg bw/d","noael_value":"= 242","page":63,"route":"oral","species":"rat","study_id":"sccs_o_247_noael_047"}
UnifiedCodex:SCCS_SHADOW:beta.noael_studies	developmental toxicity	660	mg/kg	rat	oral	105 weeks	developmental toxicity	SOURCE_SUBDIR=sccs_o_247; REPORT_TITLE=Final Opinion Scientific Committee on Consumer Safety SCCS OPINION on Benzophenone-3 (CAS No 131-57-7, EC No 205-031-5); OPINION_NUMBER=SCCS/1625/20; COMMITTEE=Scientific Committee on Consumer Safety (SCCS); REPORT_DATE=31 March 2021; VALUE_TEXT=660; DOSE=2010-2012 (final report in 2020) Ref 21 in submission dossier GLP | Rat Sprague- Dawley | Oral Food | 0,1000,300 0and 10 000, ppm, i.e. ± 70, 206 and 660 mg/kg/ bw/day during gestation and 157, 478 and 1609 mg/kg bw/day during lactation . from GD6 until PND 21 for F0 and then during 105 weeks for F1 observatio n at PND1, 4, 7 , 14 and 21 | 35-42...; EFFECT=Unlabeled table on page 64: - 4 - NTP modified 1- gen study equivalent to perinatal developmen tal tox study Study period : 2010-2012 (final report in 2020) Ref 21 in submission dossier GLP | Rat Sprague- Dawley | Oral Food | 0,1000,300 0and 10 000, ppm, i.e. ± 70, 206 and 660 mg/kg/ bw/day during gestation and 157, 478 and 1609 mg/kg bw/day during lactation . from GD6 until PND 21 for F0 and then during 105 weeks for F1 observatio n at PND1, 4, 7 , 14 and 21 | 35-42 femal es for F0 and 50-60 for F1 (m and f) | At 10 000 ppm: ↓ body weights gain in F0 at GD6- 9 and lactation day 4-21 At 3000 ppm: ↓ body weights gain in F0 at GD 18 -21 ↓ body weights of F1 m and f at 10 000 ppm over the course of the study and at 3000 ppm in f at week 77 | No effects on number of pups, litter size, sex distribution, In female F1: ↑ stromal polyp and endometrium hyperplasia ppm in the uterus at 3000 In male F1: ↑ fibirnoid necrosis of the arterioles at 10 000 ppm at the end of the 2 years | No teratogenic effects except at the highest dose: skeletal aberrations in the presence of maternal toxicity |...; CITATION_NUMBERS=[]; DETAILS_JSON={"cas_number":"131-57-7","citation":"","dose":"2010-2012 (final report in 2020) Ref 21 in submission dossier GLP | Rat Sprague- Dawley | Oral Food | 0,1000,300 0and 10 000, ppm, i.e. ± 70, 206 and 660 mg/kg/ bw/day during gestation and 157, 478 and 1609 mg/kg bw/day during lactation . from GD6 until PND 21 for F0 and then during 105 weeks for F1 observatio n at PND1, 4, 7 , 14 and 21 | 35-42...","duration":"105 weeks","effect":"Unlabeled table on page 64: - 4 - NTP modified 1- gen study equivalent to perinatal developmen tal tox study Study period : 2010-2012 (final report in 2020) Ref 21 in submission dossier GLP | Rat Sprague- Dawley | Oral Food | 0,1000,300 0and 10 000, ppm, i.e. ± 70, 206 and 660 mg/kg/ bw/day during gestation and 157, 478 and 1609 mg/kg bw/day during lactation . from GD6 until PND 21 for F0 and then during 105 weeks for F1 observatio n at PND1, 4, 7 , 14 and 21 | 35-42 femal es for F0 and 50-60 for F1 (m and f) | At 10 000 ppm: ↓ body weights gain in F0 at GD6- 9 and lactation day 4-21 At 3000 ppm: ↓ body weights gain in F0 at GD 18 -21 ↓ body weights of F1 m and f at 10 000 ppm over the course of the study and at 3000 ppm in f at week 77 | No effects on number of pups, litter size, sex distribution, In female F1: ↑ stromal polyp and endometrium hyperplasia ppm in the uterus at 3000 In male F1: ↑ fibirnoid necrosis of the arterioles at 10 000 ppm at the end of the 2 years | No teratogenic effects except at the highest dose: skeletal aberrations in the presence of maternal toxicity |...","endpoint":"developmental toxicity","ingredient":", and this warrants further","loael_value":"","noael_unit":"mg/kg","noael_value":"660","page":64,"route":"oral","species":"rat","study_id":"sccs_o_247_noael_048"}
UnifiedCodex:SCCS_SHADOW:beta.noael_studies	repeated dose toxicity	1050	mg/kg bw/day	rat	oral	14d	repeated dose toxicity	SOURCE_SUBDIR=sccp_o_078; REPORT_TITLE=OPINION ON BENZOPHENONE-3 COLIPA N° S38; OPINION_NUMBER=SCCP/1069/06; COMMITTEE=SCCP; REPORT_DATE=19 December 2006; VALUE_TEXT=1050; DOSE=y: increased liver weights in males and females associated with the presence of cytoplasmic vacuolisation of hepatocytes 8,648 mg/kg bw/day: increased liver weights in males and females associated with the presence of cytoplasmic vacuolisation of hepatocytes; decreased kidney weight in males 20,796 mg/kg bw/day: reduced body weight gain; increas...; EFFECT=y: increased liver weights in males and females associated with the presence of cytoplasmic vacuolisation of hepatocytes 8,648 mg/kg bw/day: increased liver weights in males and females associated with the presence of cytoplasmic vacuolisation of hepatocytes; decreased kidney weight in males 20,796 mg/kg bw/day: reduced body weight gain; increased liver weights in males and females associated with the presence of cytoplasmic vacuolisation of hepatocytes; decreased kidney weight in males Study authors' conclusion: NOAEL (14d-oral) = 992/1050 mg/kg bw/day for the male/female mouse. Ref.: 30 B. Subacute dermal administration to rats and mice 14-day dermal toxicity in rat (1985-88) Five F344/N rats per sex and group received Benzophenone-3 at dose levels of 0, 1.25, 2.5, 5.0, 10.0, 20.0 mg/rat in acetone or lotion as vehicle for 5 days per week for 2 weeks. A constant volume of 0.25 ml/rat was applied over a fixed standard area (10%) of the interscapular region. The area was clipped 24 hours prior to initial application and weekl; CITATION=Ref.: 30 B; CITATION_NUMBERS=[30]; REFERENCE=Ref.: 30 B; DETAILS_JSON={"cas_number":"131-57-7","citation":"Ref.: 30 B","dose":"y: increased liver weights in males and females associated with the presence of cytoplasmic vacuolisation of hepatocytes 8,648 mg/kg bw/day: increased liver weights in males and females associated with the presence of cytoplasmic vacuolisation of hepatocytes; decreased kidney weight in males 20,796 mg/kg bw/day: reduced body weight gain; increas...","duration":"14d","effect":"y: increased liver weights in males and females associated with the presence of cytoplasmic vacuolisation of hepatocytes 8,648 mg/kg bw/day: increased liver weights in males and females associated with the presence of cytoplasmic vacuolisation of hepatocytes; decreased kidney weight in males 20,796 mg/kg bw/day: reduced body weight gain; increased liver weights in males and females associated with the presence of cytoplasmic vacuolisation of hepatocytes; decreased kidney weight in males Study authors' conclusion: NOAEL (14d-oral) = 992/1050 mg/kg bw/day for the male/female mouse. Ref.: 30 B. Subacute dermal administration to rats and mice 14-day dermal toxicity in rat (1985-88) Five F344/N rats per sex and group received Benzophenone-3 at dose levels of 0, 1.25, 2.5, 5.0, 10.0, 20.0 mg/rat in acetone or lotion as vehicle for 5 days per week for 2 weeks. A constant volume of 0.25 ml/rat was applied over a fixed standard area (10%) of the interscapular region. The area was clipped 24 hours prior to initial application and weekl","endpoint":"repeated dose toxicity","ingredient":"INCI name","loael_value":"","noael_unit":"mg/kg bw/day","noael_value":"1050","page":13,"route":"oral","species":"rat","study_id":"sccp_o_078_noael_002"}
UnifiedCodex:SCCS_SHADOW:beta.noael_studies	repeated dose toxicity	432	mg/kg bw/day	rat	oral	14d	repeated dose toxicity	SOURCE_SUBDIR=sccp_o_078; REPORT_TITLE=OPINION ON BENZOPHENONE-3 COLIPA N° S38; OPINION_NUMBER=SCCP/1069/06; COMMITTEE=SCCP; REPORT_DATE=19 December 2006; VALUE_TEXT=432; DOSE=24.8 mg/kg bw/day: none 48.4 mg/kg bw/day: none 100 mg/kg bw/day: none 196 mg/kg bw/day: increased liver weight 388 mg/kg bw/day: increased liver weight Study authors' conclusion:; EFFECT=tions covering clinical signs, mortality, body weight and food consumption were performed in all animals. At termination of treatment, all animals were sacrificed and macroscopically examined, organs were weighed and comprehensive histopathology was performed. The following effects were noted (applied doses were converted to dosages): 24.8 mg/kg bw/day: none 48.4 mg/kg bw/day: none 100 mg/kg bw/day: none 196 mg/kg bw/day: increased liver weight 388 mg/kg bw/day: increased liver weight Study authors' conclusion: NOAEL (14d-dermal) = 384/432 mg/kg bw/day for the male/female mouse. Ref.: 30 3.3.5.2 Sub-chronic (90 days) oral / dermal / inhalation toxicity - rat/mouse A. Sub-chronic oral administration to rats and mice 90-day oral toxicity in rat (1) (1972) Benzophenone-3 (source and batch not cited) was examined in 12 male and 12 female rats per sex and group at dosages of approximately 0, 20, 100, 500 and 1,000 mg/kg bw/day for 13 weeks. The animals were observed for clinical findings and body weight and food consumption was; CITATION=Ref.: 30 3; CITATION_NUMBERS=[30,3]; REFERENCE=Ref.: 30 3; DETAILS_JSON={"cas_number":"131-57-7","citation":"Ref.: 30 3","dose":"24.8 mg/kg bw/day: none 48.4 mg/kg bw/day: none 100 mg/kg bw/day: none 196 mg/kg bw/day: increased liver weight 388 mg/kg bw/day: increased liver weight Study authors' conclusion:","duration":"14d","effect":"tions covering clinical signs, mortality, body weight and food consumption were performed in all animals. At termination of treatment, all animals were sacrificed and macroscopically examined, organs were weighed and comprehensive histopathology was performed. The following effects were noted (applied doses were converted to dosages): 24.8 mg/kg bw/day: none 48.4 mg/kg bw/day: none 100 mg/kg bw/day: none 196 mg/kg bw/day: increased liver weight 388 mg/kg bw/day: increased liver weight Study authors' conclusion: NOAEL (14d-dermal) = 384/432 mg/kg bw/day for the male/female mouse. Ref.: 30 3.3.5.2 Sub-chronic (90 days) oral / dermal / inhalation toxicity - rat/mouse A. Sub-chronic oral administration to rats and mice 90-day oral toxicity in rat (1) (1972) Benzophenone-3 (source and batch not cited) was examined in 12 male and 12 female rats per sex and group at dosages of approximately 0, 20, 100, 500 and 1,000 mg/kg bw/day for 13 weeks. The animals were observed for clinical findings and body weight and food consumption was","endpoint":"repeated dose toxicity","ingredient":"INCI name","loael_value":"","noael_unit":"mg/kg bw/day","noael_value":"432","page":14,"route":"oral","species":"rat","study_id":"sccp_o_078_noael_004"}
UnifiedCodex:SCCS_SHADOW:beta.noael_studies	repeated dose toxicity	1425	mg/kg bw/day	rat	oral	90d	repeated dose toxicity	SOURCE_SUBDIR=sccp_o_078; REPORT_TITLE=OPINION ON BENZOPHENONE-3 COLIPA N° S38; OPINION_NUMBER=SCCP/1069/06; COMMITTEE=SCCP; REPORT_DATE=19 December 2006; VALUE_TEXT=1425; DOSE=y: increased liver weight 2,860 mg/kg bw/day: increased liver weight 6,780 mg/kg bw/day: decreased body weight gain in males and females; increased liver weight; minimal cytoplasmic vacuolisation of hepatocytes 16,238 mg/kg bw/day: decreased body weight gain in males and females; minimal renal lesions in males; increased liver weight; minimal cy...; EFFECT=y: increased liver weight 2,860 mg/kg bw/day: increased liver weight 6,780 mg/kg bw/day: decreased body weight gain in males and females; increased liver weight; minimal cytoplasmic vacuolisation of hepatocytes 16,238 mg/kg bw/day: decreased body weight gain in males and females; minimal renal lesions in males; increased liver weight; minimal cytoplasmic vacuolisation of hepatocytes; decreased sperm density and increased abnormal sperm in males; increased estrous cycle length in females Study authors' conclusion: NOAEL (90d-oral) = 1068/1425 mg/kg bw/day for the male/female mouse. Ref.: 30 B. Sub-chronic dermal administration to rats and mice 90-day dermal toxicity in rat (1985-88) Ten F344/N rats per sex and groups received Benzophenone-3 preparations at dosage levels of 0, 12.5, 25, 50, 100, 200 mg/kg bw/day in acetone for 5 days per week over a period of 13 weeks. A constant volume of 0.25 ml/rat was applied over a fixed standard area (10%) of the interscapular region. The area was clipped 24 hours prior to initial applic; CITATION=Ref.: 30 B; CITATION_NUMBERS=[30]; REFERENCE=Ref.: 30 B; DETAILS_JSON={"cas_number":"131-57-7","citation":"Ref.: 30 B","dose":"y: increased liver weight 2,860 mg/kg bw/day: increased liver weight 6,780 mg/kg bw/day: decreased body weight gain in males and females; increased liver weight; minimal cytoplasmic vacuolisation of hepatocytes 16,238 mg/kg bw/day: decreased body weight gain in males and females; minimal renal lesions in males; increased liver weight; minimal cy...","duration":"90d","effect":"y: increased liver weight 2,860 mg/kg bw/day: increased liver weight 6,780 mg/kg bw/day: decreased body weight gain in males and females; increased liver weight; minimal cytoplasmic vacuolisation of hepatocytes 16,238 mg/kg bw/day: decreased body weight gain in males and females; minimal renal lesions in males; increased liver weight; minimal cytoplasmic vacuolisation of hepatocytes; decreased sperm density and increased abnormal sperm in males; increased estrous cycle length in females Study authors' conclusion: NOAEL (90d-oral) = 1068/1425 mg/kg bw/day for the male/female mouse. Ref.: 30 B. Sub-chronic dermal administration to rats and mice 90-day dermal toxicity in rat (1985-88) Ten F344/N rats per sex and groups received Benzophenone-3 preparations at dosage levels of 0, 12.5, 25, 50, 100, 200 mg/kg bw/day in acetone for 5 days per week over a period of 13 weeks. A constant volume of 0.25 ml/rat was applied over a fixed standard area (10%) of the interscapular region. The area was clipped 24 hours prior to initial applic","endpoint":"repeated dose toxicity","ingredient":"INCI name","loael_value":"","noael_unit":"mg/kg bw/day","noael_value":"1425","page":17,"route":"oral","species":"rat","study_id":"sccp_o_078_noael_007"}
UnifiedCodex:SCCS_SHADOW:beta.noael_studies	repeated dose toxicity	=364	mg/kg bw/day	rat	oral	90d	repeated dose toxicity	SOURCE_SUBDIR=sccp_o_078; REPORT_TITLE=OPINION ON BENZOPHENONE-3 COLIPA N° S38; OPINION_NUMBER=SCCP/1069/06; COMMITTEE=SCCP; REPORT_DATE=19 December 2006; VALUE_TEXT== 364; DOSE=Sperm morphology/motility and vaginal cytology examinations were performed at dosage levels of 0, 22.8, 91, 364 mg/kg bw/day.; EFFECT=ll animals at regular intervals. Sperm morphology/motility and vaginal cytology examinations were performed at dosage levels of 0, 22.8, 91, 364 mg/kg bw/day. At termination of treatment, all animals were sacrificed and macroscopically examined, organs were weighed and comprehensive histopathology was performed. At all dosage levels, a mild increase in relative kidney weight in males, together with a decrease in epididymal sperm density, was noted. No other abnormalities were observed. Study authors' conclusion: NOAEL (90d-dermal) = 364 mg/kg bw/day for male and female mice. Ref.: 30 3.3.5.3 Chronic (> 12 months) toxicity No data. 3.3.5.4 Overall conclusion of the submission authors on repeated dose toxicity The toxicity of Benzophenone-3 after repeated application was comprehensively examined in subacute up to subchronic studies in rats and mice using the oral and dermal application route. The systemic toxicity after repeated oral application was low and effects could mainly be observed at dose levels which were in the ran; CITATION=Ref.: 30 3; CITATION_NUMBERS=[30,3]; REFERENCE=Ref.: 30 3; DETAILS_JSON={"cas_number":"131-57-7","citation":"Ref.: 30 3","dose":"Sperm morphology/motility and vaginal cytology examinations were performed at dosage levels of 0, 22.8, 91, 364 mg/kg bw/day.","duration":"90d","effect":"ll animals at regular intervals. Sperm morphology/motility and vaginal cytology examinations were performed at dosage levels of 0, 22.8, 91, 364 mg/kg bw/day. At termination of treatment, all animals were sacrificed and macroscopically examined, organs were weighed and comprehensive histopathology was performed. At all dosage levels, a mild increase in relative kidney weight in males, together with a decrease in epididymal sperm density, was noted. No other abnormalities were observed. Study authors' conclusion: NOAEL (90d-dermal) = 364 mg/kg bw/day for male and female mice. Ref.: 30 3.3.5.3 Chronic (> 12 months) toxicity No data. 3.3.5.4 Overall conclusion of the submission authors on repeated dose toxicity The toxicity of Benzophenone-3 after repeated application was comprehensively examined in subacute up to subchronic studies in rats and mice using the oral and dermal application route. The systemic toxicity after repeated oral application was low and effects could mainly be observed at dose levels which were in the ran","endpoint":"repeated dose toxicity","ingredient":"INCI name","loael_value":"","noael_unit":"mg/kg bw/day","noael_value":"= 364","page":18,"route":"oral","species":"rat","study_id":"sccp_o_078_noael_009"}
UnifiedCodex:SCCS_SHADOW:beta.noael_studies	repeated dose toxicity	6250	ppm	rat	oral	subchronic	repeated dose toxicity	SOURCE_SUBDIR=sccp_o_078; REPORT_TITLE=OPINION ON BENZOPHENONE-3 COLIPA N° S38; OPINION_NUMBER=SCCP/1069/06; COMMITTEE=SCCP; REPORT_DATE=19 December 2006; VALUE_TEXT=6250; DOSE=ly >3000 mg/kg bw/day in rats and >13000 mg/kg bw/day in mice after subchronic oral treatment, an impairment of selective reproductive parameters was noted.; EFFECT=ly >3000 mg/kg bw/day in rats and >13000 mg/kg bw/day in mice after subchronic oral treatment, an impairment of selective reproductive parameters was noted. However, these are finally assessed in the reproduction section within this dossier (section 3.3.8 Reproductive toxicity). Repeated dermal application of up to 13 weeks in rats and mice did not lead to any reliable substance-related local or systemic findings up to the highest dose level investigated in each case. Finally, the reliable No-Adverse-Effect-Level (NOAEL) for subchronic toxicity after oral treatment was 6250 ppm (429/393 mg/kg bw/day in males/females) in rats and 6250 ppm (1068/1425 mg/kg bw/day in males/females) in mice.; CITATION_NUMBERS=[]; DETAILS_JSON={"cas_number":"131-57-7","citation":"","dose":"ly >3000 mg/kg bw/day in rats and >13000 mg/kg bw/day in mice after subchronic oral treatment, an impairment of selective reproductive parameters was noted.","duration":"subchronic","effect":"ly >3000 mg/kg bw/day in rats and >13000 mg/kg bw/day in mice after subchronic oral treatment, an impairment of selective reproductive parameters was noted. However, these are finally assessed in the reproduction section within this dossier (section 3.3.8 Reproductive toxicity). Repeated dermal application of up to 13 weeks in rats and mice did not lead to any reliable substance-related local or systemic findings up to the highest dose level investigated in each case. Finally, the reliable No-Adverse-Effect-Level (NOAEL) for subchronic toxicity after oral treatment was 6250 ppm (429/393 mg/kg bw/day in males/females) in rats and 6250 ppm (1068/1425 mg/kg bw/day in males/females) in mice.","endpoint":"repeated dose toxicity","ingredient":"INCI name","loael_value":"","noael_unit":"ppm","noael_value":"6250","page":18,"route":"oral","species":"rat","study_id":"sccp_o_078_noael_010"}
UnifiedCodex:SCCS_SHADOW:beta.noael_studies	repeated dose toxicity	200	mg/kg bw/day	rat	dermal	subchronic	repeated dose toxicity	SOURCE_SUBDIR=sccp_o_078; REPORT_TITLE=OPINION ON BENZOPHENONE-3 COLIPA N° S38; OPINION_NUMBER=SCCP/1069/06; COMMITTEE=SCCP; REPORT_DATE=19 December 2006; VALUE_TEXT=200; DOSE=SCCP/1069/06 OPINION ON BENZOPHENONE-3 19 For subchronic dermal treatment in each case the highest dose level was the reliable No- Adverse-Effect-Level (NOAEL), namely 200 mg/kg bw/day in rats and 364 mg/kg bw/day in mice.; EFFECT=SCCP/1069/06 OPINION ON BENZOPHENONE-3 19 For subchronic dermal treatment in each case the highest dose level was the reliable No- Adverse-Effect-Level (NOAEL), namely 200 mg/kg bw/day in rats and 364 mg/kg bw/day in mice. 3.3.6 Mutagenicity / genotoxicity 3.3.6.1 Mutagenicity/Genotoxicity in vitro A. In vitro bacterial mutation assay (Ames test) A number of publications (1980-1992) describe the results of Benzophenone-3 studied in the Ames test. The level of detail provided in these publications ranges from a summary and a title page [36] to a more extensive description of the materials and methods [73]. Generally the test substance was tested for mutagenicity in t; CITATION_NUMBERS=[]; DETAILS_JSON={"cas_number":"131-57-7","citation":"","dose":"SCCP/1069/06 OPINION ON BENZOPHENONE-3 19 For subchronic dermal treatment in each case the highest dose level was the reliable No- Adverse-Effect-Level (NOAEL), namely 200 mg/kg bw/day in rats and 364 mg/kg bw/day in mice.","duration":"subchronic","effect":"SCCP/1069/06 OPINION ON BENZOPHENONE-3 19 For subchronic dermal treatment in each case the highest dose level was the reliable No- Adverse-Effect-Level (NOAEL), namely 200 mg/kg bw/day in rats and 364 mg/kg bw/day in mice. 3.3.6 Mutagenicity / genotoxicity 3.3.6.1 Mutagenicity/Genotoxicity in vitro A. In vitro bacterial mutation assay (Ames test) A number of publications (1980-1992) describe the results of Benzophenone-3 studied in the Ames test. The level of detail provided in these publications ranges from a summary and a title page [36] to a more extensive description of the materials and methods [73]. Generally the test substance was tested for mutagenicity in t","endpoint":"repeated dose toxicity","ingredient":"INCI name","loael_value":"","noael_unit":"mg/kg bw/day","noael_value":"200","page":19,"route":"dermal","species":"rat","study_id":"sccp_o_078_noael_011"}
UnifiedCodex:SCCS_SHADOW:beta.noael_studies	repeated dose toxicity	=400	mg/kg bw/day	mouse	oral	sub-chronic	repeated dose toxicity	SOURCE_SUBDIR=sccp_o_078; REPORT_TITLE=OPINION ON BENZOPHENONE-3 COLIPA N° S38; OPINION_NUMBER=SCCP/1069/06; COMMITTEE=SCCP; REPORT_DATE=19 December 2006; VALUE_TEXT== 400; DOSE=Since neither any effect on body weight gain nor any abnormalities in the measured reproductive parameters were noted, the study authors conclude that topically applied Benzophenone-3 has no reproductive toxic potential in male B6C3F1 mice at dosages up to 400 mg/kg bw/day.; EFFECT=0 mg/kg bw/day. Reproductive organ weights, cauda epididymal sperm concentration, proportion of motile and abnormal sperm and testicular spermatid concentration were determined and testicular histology was evaluated. Since neither any effect on body weight gain nor any abnormalities in the measured reproductive parameters were noted, the study authors conclude that topically applied Benzophenone-3 has no reproductive toxic potential in male B6C3F1 mice at dosages up to 400 mg/kg bw/day. Study authors' conclusion: NOAEL (reproduction) = 400 mg/kg bw/day for male and female mice. Ref.: 21 Finally, the results of the examinations of sperm morphology/motility and vaginal cytology in the dermal sub-chronic toxicity studies as described under 3.3.5.2.B, revealed a decrease in epididymal sperm density in the male mice. However, this finding is considered incidental 3 Stability of Benzophenone-3 in the diet : at least 3 weeks; CITATION=Ref.: 21 Finally, the results of the examinations of sperm morphology/motility and vaginal cytology in the dermal sub-chronic toxicity studies as described under 3; CITATION_NUMBERS=[21,3]; REFERENCE=Ref.: 21 Finally, the results of the examinations of sperm morphology/motility and vaginal cytology in the dermal sub-chronic toxicity studies as described under 3; DETAILS_JSON={"cas_number":"131-57-7","citation":"Ref.: 21 Finally, the results of the examinations of sperm morphology/motility and vaginal cytology in the dermal sub-chronic toxicity studies as described under 3","dose":"Since neither any effect on body weight gain nor any abnormalities in the measured reproductive parameters were noted, the study authors conclude that topically applied Benzophenone-3 has no reproductive toxic potential in male B6C3F1 mice at dosages up to 400 mg/kg bw/day.","duration":"sub-chronic","effect":"0 mg/kg bw/day. Reproductive organ weights, cauda epididymal sperm concentration, proportion of motile and abnormal sperm and testicular spermatid concentration were determined and testicular histology was evaluated. Since neither any effect on body weight gain nor any abnormalities in the measured reproductive parameters were noted, the study authors conclude that topically applied Benzophenone-3 has no reproductive toxic potential in male B6C3F1 mice at dosages up to 400 mg/kg bw/day. Study authors' conclusion: NOAEL (reproduction) = 400 mg/kg bw/day for male and female mice. Ref.: 21 Finally, the results of the examinations of sperm morphology/motility and vaginal cytology in the dermal sub-chronic toxicity studies as described under 3.3.5.2.B, revealed a decrease in epididymal sperm density in the male mice. However, this finding is considered incidental 3 Stability of Benzophenone-3 in the diet : at least 3 weeks","endpoint":"repeated dose toxicity","ingredient":"INCI name","loael_value":"","noael_unit":"mg/kg bw/day","noael_value":"= 400","page":23,"route":"oral","species":"mouse","study_id":"sccp_o_078_noael_015"}
UnifiedCodex:SCCS_SHADOW:beta.noael_studies	repeated dose toxicity	200	mg/kg bw/d	rat	oral	subchronic	repeated dose toxicity	SOURCE_SUBDIR=sccp_o_078; REPORT_TITLE=OPINION ON BENZOPHENONE-3 COLIPA N° S38; OPINION_NUMBER=SCCP/1069/06; COMMITTEE=SCCP; REPORT_DATE=19 December 2006; VALUE_TEXT=200; DOSE=In any case, the next lower investigated dose level was a clear NOAEL for the investigated reproductive parameters.; EFFECT=ecreased absolute cauda, epididymal and testis weight as a consequence of the reduced body weight was noted. In female rats, an increase in the length of the oestrous cycle was noted. In mice, a decrease in the epididymal sperm count and an increase the incidence of abnormal sperm was recorded, while female mice (as in rats) revealed an increase in the length of the oestrous cycle. However, in rats and in mice, the oestrous cyclicity was not affected. In any case, the next lower investigated dose level was a clear NOAEL for the investigated reproductive parameters. After subchronic dermal application for 13 weeks no clear or reliable effect on selective reproduction parameter was noted and therefore, the NOAEL was in each case the highest dose level applied, namely 200 mg/kg bw/d in rats and 364 mg/kg bw/d in mice. Although in mice a decrease in the epididymal sperm count was reported at all investigated dose levels, a relation to treatment is considered as very unlikely since in the oral study the administration of dose levels; CITATION_NUMBERS=[]; DETAILS_JSON={"cas_number":"131-57-7","citation":"","dose":"In any case, the next lower investigated dose level was a clear NOAEL for the investigated reproductive parameters.","duration":"subchronic","effect":"ecreased absolute cauda, epididymal and testis weight as a consequence of the reduced body weight was noted. In female rats, an increase in the length of the oestrous cycle was noted. In mice, a decrease in the epididymal sperm count and an increase the incidence of abnormal sperm was recorded, while female mice (as in rats) revealed an increase in the length of the oestrous cycle. However, in rats and in mice, the oestrous cyclicity was not affected. In any case, the next lower investigated dose level was a clear NOAEL for the investigated reproductive parameters. After subchronic dermal application for 13 weeks no clear or reliable effect on selective reproduction parameter was noted and therefore, the NOAEL was in each case the highest dose level applied, namely 200 mg/kg bw/d in rats and 364 mg/kg bw/d in mice. Although in mice a decrease in the epididymal sperm count was reported at all investigated dose levels, a relation to treatment is considered as very unlikely since in the oral study the administration of dose levels","endpoint":"repeated dose toxicity","ingredient":"INCI name","loael_value":"","noael_unit":"mg/kg bw/d","noael_value":"200","page":25,"route":"oral","species":"rat","study_id":"sccp_o_078_noael_020"}
UnifiedCodex:SCCS_SHADOW:beta.noael_studies	repeated dose toxicity	200	mg/kg bw/d	rat	oral	subchronic	repeated dose toxicity	SOURCE_SUBDIR=sccp_o_078; REPORT_TITLE=OPINION ON BENZOPHENONE-3 COLIPA N° S38; OPINION_NUMBER=SCCP/1069/06; COMMITTEE=SCCP; REPORT_DATE=19 December 2006; VALUE_TEXT=200; DOSE=In any case, the next lower investigated dose level was a clear NOAEL for the investigated reproductive parameters.; EFFECT=decrease in the epididymal sperm count and an increase the incidence of abnormal sperm was recorded, while female mice (as in rats) revealed an increase in the length of the oestrous cycle. However, in rats and in mice, the oestrous cyclicity was not affected. In any case, the next lower investigated dose level was a clear NOAEL for the investigated reproductive parameters. After subchronic dermal application for 13 weeks no clear or reliable effect on selective reproduction parameter was noted and therefore, the NOAEL was in each case the highest dose level applied, namely 200 mg/kg bw/d in rats and 364 mg/kg bw/d in mice. Although in mice a decrease in the epididymal sperm count was reported at all investigated dose levels, a relation to treatment is considered as very unlikely since in the oral study the administration of dose levels up to 16-fold higher had no effect. Moreover, repeated dermal application of Benzophenone-3 to male mice of another strain for the same period led to no signs of reproductive toxicity up to the s; CITATION_NUMBERS=[]; DETAILS_JSON={"cas_number":"131-57-7","citation":"","dose":"In any case, the next lower investigated dose level was a clear NOAEL for the investigated reproductive parameters.","duration":"subchronic","effect":"decrease in the epididymal sperm count and an increase the incidence of abnormal sperm was recorded, while female mice (as in rats) revealed an increase in the length of the oestrous cycle. However, in rats and in mice, the oestrous cyclicity was not affected. In any case, the next lower investigated dose level was a clear NOAEL for the investigated reproductive parameters. After subchronic dermal application for 13 weeks no clear or reliable effect on selective reproduction parameter was noted and therefore, the NOAEL was in each case the highest dose level applied, namely 200 mg/kg bw/d in rats and 364 mg/kg bw/d in mice. Although in mice a decrease in the epididymal sperm count was reported at all investigated dose levels, a relation to treatment is considered as very unlikely since in the oral study the administration of dose levels up to 16-fold higher had no effect. Moreover, repeated dermal application of Benzophenone-3 to male mice of another strain for the same period led to no signs of reproductive toxicity up to the s","endpoint":"repeated dose toxicity","ingredient":"INCI name","loael_value":"","noael_unit":"mg/kg bw/d","noael_value":"200","page":25,"route":"oral","species":"rat","study_id":"sccp_o_078_noael_021"}
UnifiedCodex:SCCS_SHADOW:beta.noael_studies	repeated dose toxicity	411	mg/kg bw/day	rat	oral	90d	repeated dose toxicity	SOURCE_SUBDIR=sccp_o_078; REPORT_TITLE=OPINION ON BENZOPHENONE-3 COLIPA N° S38; OPINION_NUMBER=SCCP/1069/06; COMMITTEE=SCCP; REPORT_DATE=19 December 2006; VALUE_TEXT=411; DOSE=Therefore, according to the submission, the oral NOAEL corresponds to 411 mg/kg bw/day.; EFFECT=SCCS-rejected applicant NOAEL: ether with some effects on the identified target organs being the kidney and the liver. These effects were partly associated with changes in clinical chemistry. Very often the most susceptible parameter was the increase in liver weight. The latter, however, without any histopathological correlate, is not considered by the submission authors to reflect an adverse effect per se but should be considered as an adaptive metabolic response which is known to be reversible. Therefore, according to the submission, the oral NOAEL corresponds to 411 mg/kg bw/day. With regard to the results of the dermal repeated dose studies, a dermal NOAEL of 200 mg/kg bw/day is put forward, on the assumption that deviations without dose-response relationship and without correlated histopathological findings (e.g. the decreased reticulocyte count, increased relative kidney weight, increased platelet count and whole blood cell count in the 90d dermal study in rat) should not be taken into account.; CITATION_NUMBERS=[]; DETAILS_JSON={"cas_number":"131-57-7","citation":"","dose":"Therefore, according to the submission, the oral NOAEL corresponds to 411 mg/kg bw/day.","duration":"90d","effect":"SCCS-rejected applicant NOAEL: ether with some effects on the identified target organs being the kidney and the liver. These effects were partly associated with changes in clinical chemistry. Very often the most susceptible parameter was the increase in liver weight. The latter, however, without any histopathological correlate, is not considered by the submission authors to reflect an adverse effect per se but should be considered as an adaptive metabolic response which is known to be reversible. Therefore, according to the submission, the oral NOAEL corresponds to 411 mg/kg bw/day. With regard to the results of the dermal repeated dose studies, a dermal NOAEL of 200 mg/kg bw/day is put forward, on the assumption that deviations without dose-response relationship and without correlated histopathological findings (e.g. the decreased reticulocyte count, increased relative kidney weight, increased platelet count and whole blood cell count in the 90d dermal study in rat) should not be taken into account.","endpoint":"repeated dose toxicity","ingredient":"INCI name","loael_value":"","noael_unit":"mg/kg bw/day","noael_value":"411","page":35,"route":"oral","species":"rat","study_id":"sccp_o_078_noael_023"}
UnifiedCodex:SCCS_SHADOW:beta.noael_studies	repeated dose toxicity	200	mg/kg bw/day	rat	oral	90d	repeated dose toxicity	SOURCE_SUBDIR=sccp_o_078; REPORT_TITLE=OPINION ON BENZOPHENONE-3 COLIPA N° S38; OPINION_NUMBER=SCCP/1069/06; COMMITTEE=SCCP; REPORT_DATE=19 December 2006; VALUE_TEXT=200; DOSE=Therefore, according to the submission, the oral NOAEL corresponds to 411 mg/kg bw/day.; EFFECT=SCCS-rejected applicant NOAEL: associated with changes in clinical chemistry. Very often the most susceptible parameter was the increase in liver weight. The latter, however, without any histopathological correlate, is not considered by the submission authors to reflect an adverse effect per se but should be considered as an adaptive metabolic response which is known to be reversible. Therefore, according to the submission, the oral NOAEL corresponds to 411 mg/kg bw/day. With regard to the results of the dermal repeated dose studies, a dermal NOAEL of 200 mg/kg bw/day is put forward, on the assumption that deviations without dose-response relationship and without correlated histopathological findings (e.g. the decreased reticulocyte count, increased relative kidney weight, increased platelet count and whole blood cell count in the 90d dermal study in rat) should not be taken into account.; CITATION_NUMBERS=[]; DETAILS_JSON={"cas_number":"131-57-7","citation":"","dose":"Therefore, according to the submission, the oral NOAEL corresponds to 411 mg/kg bw/day.","duration":"90d","effect":"SCCS-rejected applicant NOAEL: associated with changes in clinical chemistry. Very often the most susceptible parameter was the increase in liver weight. The latter, however, without any histopathological correlate, is not considered by the submission authors to reflect an adverse effect per se but should be considered as an adaptive metabolic response which is known to be reversible. Therefore, according to the submission, the oral NOAEL corresponds to 411 mg/kg bw/day. With regard to the results of the dermal repeated dose studies, a dermal NOAEL of 200 mg/kg bw/day is put forward, on the assumption that deviations without dose-response relationship and without correlated histopathological findings (e.g. the decreased reticulocyte count, increased relative kidney weight, increased platelet count and whole blood cell count in the 90d dermal study in rat) should not be taken into account.","endpoint":"repeated dose toxicity","ingredient":"INCI name","loael_value":"","noael_unit":"mg/kg bw/day","noael_value":"200","page":35,"route":"oral","species":"rat","study_id":"sccp_o_078_noael_024"}
UnifiedCodex:SCCS_SHADOW:beta.noael_studies	repeated dose toxicity	200	mg/kg bw/day	rat	oral	developmental	repeated dose toxicity	SOURCE_SUBDIR=sccp_o_078; REPORT_TITLE=OPINION ON BENZOPHENONE-3 COLIPA N° S38; OPINION_NUMBER=SCCP/1069/06; COMMITTEE=SCCP; REPORT_DATE=19 December 2006; VALUE_TEXT=200; DOSE=The NOAEL- value for maternal and developmental toxicity was 200 mg/kg bw/day.; EFFECT=compared to oral administration, the dermal dosages remain at the low side and this is also confirmed by the absence of clear toxicity signs at the highest levels tested (as requested in the official EC B.9/OECD 410 and EC B.28/OECD 411 testing guidelines). A recently performed and well-described teratogenicity study in rat showed Benzophenone- 3 to be non-teratogenic under the conditions of the test. Only at the highest dosage level, which also caused maternal toxicity, some skeletal aberrations were noted. The NOAEL- value for maternal and developmental toxicity was 200 mg/kg bw/day. Instead of a 2-generation study, the submission contains some specific reproductive toxicity parameter measurements made at the end of the subchronic toxicity studies described earlier, together with the description of a reproduction screening assay according to the "Continuous Breeding Protocol". Out of these results, a NOAEL value of 400 mg/kg bw/day for reproductive toxicity, was extracted. Although the test is not commonly performed within t; CITATION_NUMBERS=[]; DETAILS_JSON={"cas_number":"131-57-7","citation":"","dose":"The NOAEL- value for maternal and developmental toxicity was 200 mg/kg bw/day.","duration":"developmental","effect":"compared to oral administration, the dermal dosages remain at the low side and this is also confirmed by the absence of clear toxicity signs at the highest levels tested (as requested in the official EC B.9/OECD 410 and EC B.28/OECD 411 testing guidelines). A recently performed and well-described teratogenicity study in rat showed Benzophenone- 3 to be non-teratogenic under the conditions of the test. Only at the highest dosage level, which also caused maternal toxicity, some skeletal aberrations were noted. The NOAEL- value for maternal and developmental toxicity was 200 mg/kg bw/day. Instead of a 2-generation study, the submission contains some specific reproductive toxicity parameter measurements made at the end of the subchronic toxicity studies described earlier, together with the description of a reproduction screening assay according to the \"Continuous Breeding Protocol\". Out of these results, a NOAEL value of 400 mg/kg bw/day for reproductive toxicity, was extracted. Although the test is not commonly performed within t","endpoint":"repeated dose toxicity","ingredient":"INCI name","loael_value":"","noael_unit":"mg/kg bw/day","noael_value":"200","page":36,"route":"oral","species":"rat","study_id":"sccp_o_078_noael_025"}
UnifiedCodex:SCCS_SHADOW:beta.noael_studies	repeated dose toxicity	400	mg/kg bw/day	-	-	developmental	repeated dose toxicity	SOURCE_SUBDIR=sccp_o_078; REPORT_TITLE=OPINION ON BENZOPHENONE-3 COLIPA N° S38; OPINION_NUMBER=SCCP/1069/06; COMMITTEE=SCCP; REPORT_DATE=19 December 2006; VALUE_TEXT=400; DOSE=The NOAEL- value for maternal and developmental toxicity was 200 mg/kg bw/day.; EFFECT=e test. Only at the highest dosage level, which also caused maternal toxicity, some skeletal aberrations were noted. The NOAEL- value for maternal and developmental toxicity was 200 mg/kg bw/day. Instead of a 2-generation study, the submission contains some specific reproductive toxicity parameter measurements made at the end of the subchronic toxicity studies described earlier, together with the description of a reproduction screening assay according to the "Continuous Breeding Protocol". Out of these results, a NOAEL value of 400 mg/kg bw/day for reproductive toxicity, was extracted. Although the test is not commonly performed within the EU regulatory framework and although a number of animals in all dosage groups unexpectedly died, it does not seem to be acceptable from an ethical point of view, to request a new 2-generation study with Benzophenone-3. Toxicokinetic studies indicate that Benzophenone-3 is readily biotransformed into its three major metabolites 2,4-Dihydroxybenzone (DHB), 2,2'-dihydroxy-4-methoxybenzone (DHMB); CITATION_NUMBERS=[]; DETAILS_JSON={"cas_number":"131-57-7","citation":"","dose":"The NOAEL- value for maternal and developmental toxicity was 200 mg/kg bw/day.","duration":"developmental","effect":"e test. Only at the highest dosage level, which also caused maternal toxicity, some skeletal aberrations were noted. The NOAEL- value for maternal and developmental toxicity was 200 mg/kg bw/day. Instead of a 2-generation study, the submission contains some specific reproductive toxicity parameter measurements made at the end of the subchronic toxicity studies described earlier, together with the description of a reproduction screening assay according to the \"Continuous Breeding Protocol\". Out of these results, a NOAEL value of 400 mg/kg bw/day for reproductive toxicity, was extracted. Although the test is not commonly performed within the EU regulatory framework and although a number of animals in all dosage groups unexpectedly died, it does not seem to be acceptable from an ethical point of view, to request a new 2-generation study with Benzophenone-3. Toxicokinetic studies indicate that Benzophenone-3 is readily biotransformed into its three major metabolites 2,4-Dihydroxybenzone (DHB), 2,2'-dihydroxy-4-methoxybenzone (DHMB)","endpoint":"repeated dose toxicity","ingredient":"INCI name","loael_value":"","noael_unit":"mg/kg bw/day","noael_value":"400","page":36,"route":"","species":"","study_id":"sccp_o_078_noael_026"}
UnifiedCodex:SCCS_SHADOW:beta.noael_studies	repeated dose toxicity	18	-	-	oral	subchronic	repeated dose toxicity	SOURCE_SUBDIR=sccp_o_078; REPORT_TITLE=OPINION ON BENZOPHENONE-3 COLIPA N° S38; OPINION_NUMBER=SCCP/1069/06; COMMITTEE=SCCP; REPORT_DATE=19 December 2006; VALUE_TEXT=unclear:Unlabeled table on page 18: Finally, the reliable No-Adverse-Effect-Level (NOAEL) for subchronic toxicity after oral; EFFECT=Unlabeled table on page 18: Finally, the reliable No-Adverse-Effect-Level (NOAEL) for subchronic toxicity after oral; CITATION_NUMBERS=[]; DETAILS_JSON={"cas_number":"131-57-7","citation":"","dose":"","duration":"subchronic","effect":"Unlabeled table on page 18: Finally, the reliable No-Adverse-Effect-Level (NOAEL) for subchronic toxicity after oral","endpoint":"repeated dose toxicity","ingredient":"INCI name","loael_value":"","noael_unit":"","noael_value":"unclear:Unlabeled table on page 18: Finally, the reliable No-Adverse-Effect-Level (NOAEL) for subchronic toxicity after oral","page":18,"route":"oral","species":"","study_id":"sccp_o_078_noael_036"}
UnifiedCodex:SCCS_SHADOW:beta.noael_studies	repeated dose toxicity	35	-	-	dermal	-	repeated dose toxicity	SOURCE_SUBDIR=sccp_o_078; REPORT_TITLE=OPINION ON BENZOPHENONE-3 COLIPA N° S38; OPINION_NUMBER=SCCP/1069/06; COMMITTEE=SCCP; REPORT_DATE=19 December 2006; VALUE_TEXT=unclear:Unlabeled table on page 35: With regard to the results of the dermal repeated dose studies, a dermal NOAEL of; DOSE=With regard to the results of the dermal repeated dose studies, a dermal NOAEL of; EFFECT=Unlabeled table on page 35: With regard to the results of the dermal repeated dose studies, a dermal NOAEL of; CITATION_NUMBERS=[]; DETAILS_JSON={"cas_number":"131-57-7","citation":"","dose":"With regard to the results of the dermal repeated dose studies, a dermal NOAEL of","duration":"","effect":"Unlabeled table on page 35: With regard to the results of the dermal repeated dose studies, a dermal NOAEL of","endpoint":"repeated dose toxicity","ingredient":"INCI name","loael_value":"","noael_unit":"","noael_value":"unclear:Unlabeled table on page 35: With regard to the results of the dermal repeated dose studies, a dermal NOAEL of","page":35,"route":"dermal","species":"","study_id":"sccp_o_078_noael_081"}
UnifiedCodex:SCCS_SHADOW:beta.noael_studies	repeated dose toxicity	411	mg/kg bw/day	rat	oral	90d	repeated dose toxicity	SOURCE_SUBDIR=sccp_o_159; REPORT_TITLE=OPINION ON Benzophenone-3 COLIPA n° S38; OPINION_NUMBER=SCCP/1201/08; COMMITTEE=Scientific Committee on Consumer Products (SCCP); REPORT_DATE=16 December 2008; VALUE_TEXT=411; DOSE=Therefore, according to the 2005-submission, the oral NOAEL corresponded to 411 mg/kg bw/day.; EFFECT=SCCS-rejected applicant NOAEL: ether with effects on the identified target organs being the kidney and the liver. These effects were partly associated with changes in clinical chemistry. Very often the most susceptible parameter was the increase in liver weight. The latter, however, without any histopathological correlate, is not considered by the submission authors to reflect an adverse effect per se but should be considered as an adaptive metabolic response which is known to be reversible. Therefore, according to the 2005-submission, the oral NOAEL corresponded to 411 mg/kg bw/day. With regard to the results of the dermal repeated dose studies, a dermal NOAEL of 200 mg/kg bw/day was put forward, on the assumption that deviations without dose-response relationship and without correlated histopathological findings (e.g. the decreased reticulocyte count, increased relative kidney weight, increased platelet count and whole blood cell count in the 90d dermal study in rat) should not be taken into account. 8 A teratogenicity study in rat showed BP-3 to be non-ter; CITATION_NUMBERS=[]; DETAILS_JSON={"cas_number":"131-57-7","citation":"","dose":"Therefore, according to the 2005-submission, the oral NOAEL corresponded to 411 mg/kg bw/day.","duration":"90d","effect":"SCCS-rejected applicant NOAEL: ether with effects on the identified target organs being the kidney and the liver. These effects were partly associated with changes in clinical chemistry. Very often the most susceptible parameter was the increase in liver weight. The latter, however, without any histopathological correlate, is not considered by the submission authors to reflect an adverse effect per se but should be considered as an adaptive metabolic response which is known to be reversible. Therefore, according to the 2005-submission, the oral NOAEL corresponded to 411 mg/kg bw/day. With regard to the results of the dermal repeated dose studies, a dermal NOAEL of 200 mg/kg bw/day was put forward, on the assumption that deviations without dose-response relationship and without correlated histopathological findings (e.g. the decreased reticulocyte count, increased relative kidney weight, increased platelet count and whole blood cell count in the 90d dermal study in rat) should not be taken into account. 8 A teratogenicity study in rat showed BP-3 to be non-ter","endpoint":"repeated dose toxicity","ingredient":"2-hydroxy-4-methoxybenzophenone was submitted by COLIPA1 in December 2005.","loael_value":"","noael_unit":"mg/kg bw/day","noael_value":"411","page":6,"route":"oral","species":"rat","study_id":"sccp_o_159_noael_001"}
UnifiedCodex:SCCS_SHADOW:beta.noael_studies	repeated dose toxicity	200	mg/kg bw/day	rat	oral	90d	repeated dose toxicity	SOURCE_SUBDIR=sccp_o_159; REPORT_TITLE=OPINION ON Benzophenone-3 COLIPA n° S38; OPINION_NUMBER=SCCP/1201/08; COMMITTEE=Scientific Committee on Consumer Products (SCCP); REPORT_DATE=16 December 2008; VALUE_TEXT=200; DOSE=Therefore, according to the 2005-submission, the oral NOAEL corresponded to 411 mg/kg bw/day.; EFFECT=SCCS-rejected applicant NOAEL: ciated with changes in clinical chemistry. Very often the most susceptible parameter was the increase in liver weight. The latter, however, without any histopathological correlate, is not considered by the submission authors to reflect an adverse effect per se but should be considered as an adaptive metabolic response which is known to be reversible. Therefore, according to the 2005-submission, the oral NOAEL corresponded to 411 mg/kg bw/day. With regard to the results of the dermal repeated dose studies, a dermal NOAEL of 200 mg/kg bw/day was put forward, on the assumption that deviations without dose-response relationship and without correlated histopathological findings (e.g. the decreased reticulocyte count, increased relative kidney weight, increased platelet count and whole blood cell count in the 90d dermal study in rat) should not be taken into account. 8 A teratogenicity study in rat showed BP-3 to be non-teratogenic under the conditions of the test. Only at the highest dosage level, which also caused maternal toxicity,; CITATION_NUMBERS=[]; DETAILS_JSON={"cas_number":"131-57-7","citation":"","dose":"Therefore, according to the 2005-submission, the oral NOAEL corresponded to 411 mg/kg bw/day.","duration":"90d","effect":"SCCS-rejected applicant NOAEL: ciated with changes in clinical chemistry. Very often the most susceptible parameter was the increase in liver weight. The latter, however, without any histopathological correlate, is not considered by the submission authors to reflect an adverse effect per se but should be considered as an adaptive metabolic response which is known to be reversible. Therefore, according to the 2005-submission, the oral NOAEL corresponded to 411 mg/kg bw/day. With regard to the results of the dermal repeated dose studies, a dermal NOAEL of 200 mg/kg bw/day was put forward, on the assumption that deviations without dose-response relationship and without correlated histopathological findings (e.g. the decreased reticulocyte count, increased relative kidney weight, increased platelet count and whole blood cell count in the 90d dermal study in rat) should not be taken into account. 8 A teratogenicity study in rat showed BP-3 to be non-teratogenic under the conditions of the test. Only at the highest dosage level, which also caused maternal toxicity,","endpoint":"repeated dose toxicity","ingredient":"2-hydroxy-4-methoxybenzophenone was submitted by COLIPA1 in December 2005.","loael_value":"","noael_unit":"mg/kg bw/day","noael_value":"200","page":6,"route":"oral","species":"rat","study_id":"sccp_o_159_noael_002"}
UnifiedCodex:SCCS_SHADOW:beta.noael_studies	repeated dose toxicity	200	mg/kg bw/day	rat	-	developmental	repeated dose toxicity	SOURCE_SUBDIR=sccp_o_159; REPORT_TITLE=OPINION ON Benzophenone-3 COLIPA n° S38; OPINION_NUMBER=SCCP/1201/08; COMMITTEE=Scientific Committee on Consumer Products (SCCP); REPORT_DATE=16 December 2008; VALUE_TEXT=200; DOSE=The NOAEL-value for maternal and developmental toxicity was 200 mg/kg bw/day.; EFFECT=SCCP/1201/08 Opinion on benzophenone-3 7 skeletal aberrations were noted. The NOAEL-value for maternal and developmental toxicity was 200 mg/kg bw/day. A NOAEL value of 400 mg/kg bw/day for reproductive toxicity was extracted from subchronic toxicity studies involving additional reproductive toxicity parameter measurements. 8 Toxicokinetic studies indicated that BP-3 was readily biotransformed into its three major metabolites and that excretion in the rat primarily occurs via the urine, while in the mouse the faecal route appears to be equally important. 8 As far as the (photo)mutagenic/(photo); CITATION_NUMBERS=[]; DETAILS_JSON={"cas_number":"131-57-7","citation":"","dose":"The NOAEL-value for maternal and developmental toxicity was 200 mg/kg bw/day.","duration":"developmental","effect":"SCCP/1201/08 Opinion on benzophenone-3 7 skeletal aberrations were noted. The NOAEL-value for maternal and developmental toxicity was 200 mg/kg bw/day. A NOAEL value of 400 mg/kg bw/day for reproductive toxicity was extracted from subchronic toxicity studies involving additional reproductive toxicity parameter measurements. 8 Toxicokinetic studies indicated that BP-3 was readily biotransformed into its three major metabolites and that excretion in the rat primarily occurs via the urine, while in the mouse the faecal route appears to be equally important. 8 As far as the (photo)mutagenic/(photo)","endpoint":"repeated dose toxicity","ingredient":"2-hydroxy-4-methoxybenzophenone was submitted by COLIPA1 in December 2005.","loael_value":"","noael_unit":"mg/kg bw/day","noael_value":"200","page":7,"route":"","species":"rat","study_id":"sccp_o_159_noael_003"}
UnifiedCodex:SCCS_SHADOW:beta.noael_studies	repeated dose toxicity	411	mg/kg bw/day	rat	oral	90d	repeated dose toxicity	SOURCE_SUBDIR=sccs_o_247; REPORT_TITLE=Final Opinion Scientific Committee on Consumer Safety SCCS OPINION on Benzophenone-3 (CAS No 131-57-7, EC No 205-031-5); OPINION_NUMBER=SCCS/1625/20; COMMITTEE=Scientific Committee on Consumer Safety (SCCS); REPORT_DATE=31 March 2021; VALUE_TEXT=411; DOSE=Therefore, according to the 2005- submission, the oral NOAEL corresponded to 411 mg/kg bw/day.; EFFECT=SCCS-rejected applicant NOAEL: ther with effects on the identified target organs being the kidney and the liver. These effects were partly associated with changes in clinical chemistry. Very often the most susceptible parameter was the increase in liver weight. The latter, however, without any histopathological correlate, is not considered by the submission authors to reflect an adverse effect per se but should be considered as an adaptive metabolic response which is known to be reversible. Therefore, according to the 2005- submission, the oral NOAEL corresponded to 411 mg/kg bw/day. With regard to the results of the dermal repeated dose studies, a dermal NOAEL of 200 mg/kg bw/day was put forward, on the assumption that deviations without dose-response relationship and without correlated histopathological findings (e.g. the decreased reticulocyte count, increased relative kidney weight, increased platelet count and whole blood cell count in the 90d dermal study in rat) should not be taken into account.’ The studies already included in the previous SCCS Opinion; CITATION_NUMBERS=[]; DETAILS_JSON={"cas_number":"131-57-7","citation":"","dose":"Therefore, according to the 2005- submission, the oral NOAEL corresponded to 411 mg/kg bw/day.","duration":"90d","effect":"SCCS-rejected applicant NOAEL: ther with effects on the identified target organs being the kidney and the liver. These effects were partly associated with changes in clinical chemistry. Very often the most susceptible parameter was the increase in liver weight. The latter, however, without any histopathological correlate, is not considered by the submission authors to reflect an adverse effect per se but should be considered as an adaptive metabolic response which is known to be reversible. Therefore, according to the 2005- submission, the oral NOAEL corresponded to 411 mg/kg bw/day. With regard to the results of the dermal repeated dose studies, a dermal NOAEL of 200 mg/kg bw/day was put forward, on the assumption that deviations without dose-response relationship and without correlated histopathological findings (e.g. the decreased reticulocyte count, increased relative kidney weight, increased platelet count and whole blood cell count in the 90d dermal study in rat) should not be taken into account.’ The studies already included in the previous SCCS Opinion","endpoint":"repeated dose toxicity","ingredient":", and this warrants further","loael_value":"","noael_unit":"mg/kg bw/day","noael_value":"411","page":25,"route":"oral","species":"rat","study_id":"sccs_o_247_noael_001"}
UnifiedCodex:SCCS_SHADOW:beta.noael_studies	repeated dose toxicity	200	mg/kg bw/day	rat	oral	90d	repeated dose toxicity	SOURCE_SUBDIR=sccs_o_247; REPORT_TITLE=Final Opinion Scientific Committee on Consumer Safety SCCS OPINION on Benzophenone-3 (CAS No 131-57-7, EC No 205-031-5); OPINION_NUMBER=SCCS/1625/20; COMMITTEE=Scientific Committee on Consumer Safety (SCCS); REPORT_DATE=31 March 2021; VALUE_TEXT=200; DOSE=Therefore, according to the 2005- submission, the oral NOAEL corresponded to 411 mg/kg bw/day.; EFFECT=SCCS-rejected applicant NOAEL: iated with changes in clinical chemistry. Very often the most susceptible parameter was the increase in liver weight. The latter, however, without any histopathological correlate, is not considered by the submission authors to reflect an adverse effect per se but should be considered as an adaptive metabolic response which is known to be reversible. Therefore, according to the 2005- submission, the oral NOAEL corresponded to 411 mg/kg bw/day. With regard to the results of the dermal repeated dose studies, a dermal NOAEL of 200 mg/kg bw/day was put forward, on the assumption that deviations without dose-response relationship and without correlated histopathological findings (e.g. the decreased reticulocyte count, increased relative kidney weight, increased platelet count and whole blood cell count in the 90d dermal study in rat) should not be taken into account.’ The studies already included in the previous SCCS Opinion are not detailed in this Opinion; if they provide information on ED effects, they will be described in the secti; CITATION_NUMBERS=[]; DETAILS_JSON={"cas_number":"131-57-7","citation":"","dose":"Therefore, according to the 2005- submission, the oral NOAEL corresponded to 411 mg/kg bw/day.","duration":"90d","effect":"SCCS-rejected applicant NOAEL: iated with changes in clinical chemistry. Very often the most susceptible parameter was the increase in liver weight. The latter, however, without any histopathological correlate, is not considered by the submission authors to reflect an adverse effect per se but should be considered as an adaptive metabolic response which is known to be reversible. Therefore, according to the 2005- submission, the oral NOAEL corresponded to 411 mg/kg bw/day. With regard to the results of the dermal repeated dose studies, a dermal NOAEL of 200 mg/kg bw/day was put forward, on the assumption that deviations without dose-response relationship and without correlated histopathological findings (e.g. the decreased reticulocyte count, increased relative kidney weight, increased platelet count and whole blood cell count in the 90d dermal study in rat) should not be taken into account.’ The studies already included in the previous SCCS Opinion are not detailed in this Opinion; if they provide information on ED effects, they will be described in the secti","endpoint":"repeated dose toxicity","ingredient":", and this warrants further","loael_value":"","noael_unit":"mg/kg bw/day","noael_value":"200","page":25,"route":"oral","species":"rat","study_id":"sccs_o_247_noael_002"}
UnifiedCodex:SCCS_SHADOW:beta.noael_studies	repeated dose toxicity	200	mg/kg bw/day	rat	oral	developmental	repeated dose toxicity	SOURCE_SUBDIR=sccs_o_247; REPORT_TITLE=Final Opinion Scientific Committee on Consumer Safety SCCS OPINION on Benzophenone-3 (CAS No 131-57-7, EC No 205-031-5); OPINION_NUMBER=SCCS/1625/20; COMMITTEE=Scientific Committee on Consumer Safety (SCCS); REPORT_DATE=31 March 2021; VALUE_TEXT=200; DOSE=The NOAEL-value for maternal and developmental toxicity was 200 mg/kg bw/day.; EFFECT=ved relative liver weight increase. Analysis of a subset of estrogen-responsive genes showed no change in response to BP-3. Reproductive toxicity The 2008 SCCP Opinion (SCCP/1201/08) noted that the studies provided as part of the dossier assessed in the earlier Opinion (SCCP/1069/06) had indicated that: ‘A teratogenicity study in rats showed BP-3 to be non-teratogenic under the conditions of the test. Only at the highest dosage level, which also caused maternal toxicity, some skeletal aberrations were noted. The NOAEL-value for maternal and developmental toxicity was 200 mg/kg bw/day. A NOAEL value of 400 mg/kg bw/day for reproductive toxicity was extracted from subchronic toxicity studies involving additional reproductive toxicity parameter measurements.’ A more recent NTP modified one-generation study found that gestation body weights of dams receiving 10,000 ppm BP-3 in the diet were slightly lower (~3%) than those of the control group and showed statistically significant differences. Dams receiving 3,000 or 10,000 ppm BP-3; CITATION_NUMBERS=[]; DETAILS_JSON={"cas_number":"131-57-7","citation":"","dose":"The NOAEL-value for maternal and developmental toxicity was 200 mg/kg bw/day.","duration":"developmental","effect":"ved relative liver weight increase. Analysis of a subset of estrogen-responsive genes showed no change in response to BP-3. Reproductive toxicity The 2008 SCCP Opinion (SCCP/1201/08) noted that the studies provided as part of the dossier assessed in the earlier Opinion (SCCP/1069/06) had indicated that: ‘A teratogenicity study in rats showed BP-3 to be non-teratogenic under the conditions of the test. Only at the highest dosage level, which also caused maternal toxicity, some skeletal aberrations were noted. The NOAEL-value for maternal and developmental toxicity was 200 mg/kg bw/day. A NOAEL value of 400 mg/kg bw/day for reproductive toxicity was extracted from subchronic toxicity studies involving additional reproductive toxicity parameter measurements.’ A more recent NTP modified one-generation study found that gestation body weights of dams receiving 10,000 ppm BP-3 in the diet were slightly lower (~3%) than those of the control group and showed statistically significant differences. Dams receiving 3,000 or 10,000 ppm BP-3","endpoint":"repeated dose toxicity","ingredient":", and this warrants further","loael_value":"","noael_unit":"mg/kg bw/day","noael_value":"200","page":50,"route":"oral","species":"rat","study_id":"sccs_o_247_noael_014"}
UnifiedCodex:SCCS_SHADOW:beta.noael_studies	repeated dose toxicity	200	mg/kg bw/day	rat	oral	developmental	repeated dose toxicity	SOURCE_SUBDIR=sccs_o_247; REPORT_TITLE=Final Opinion Scientific Committee on Consumer Safety SCCS OPINION on Benzophenone-3 (CAS No 131-57-7, EC No 205-031-5); OPINION_NUMBER=SCCS/1625/20; COMMITTEE=Scientific Committee on Consumer Safety (SCCS); REPORT_DATE=31 March 2021; VALUE_TEXT=200; DOSE=The NOAEL-value for maternal and developmental toxicity was 200 mg/kg bw/day.; EFFECT=ive genes showed no change in response to BP-3. Reproductive toxicity The 2008 SCCP Opinion (SCCP/1201/08) noted that the studies provided as part of the dossier assessed in the earlier Opinion (SCCP/1069/06) had indicated that: ‘A teratogenicity study in rats showed BP-3 to be non-teratogenic under the conditions of the test. Only at the highest dosage level, which also caused maternal toxicity, some skeletal aberrations were noted. The NOAEL-value for maternal and developmental toxicity was 200 mg/kg bw/day. A NOAEL value of 400 mg/kg bw/day for reproductive toxicity was extracted from subchronic toxicity studies involving additional reproductive toxicity parameter measurements.’ A more recent NTP modified one-generation study found that gestation body weights of dams receiving 10,000 ppm BP-3 in the diet were slightly lower (~3%) than those of the control group and showed statistically significant differences. Dams receiving 3,000 or 10,000 ppm BP-3 in the diet displayed slight decreases in GD 6–21 body weight gain (~10%) r; CITATION_NUMBERS=[]; DETAILS_JSON={"cas_number":"131-57-7","citation":"","dose":"The NOAEL-value for maternal and developmental toxicity was 200 mg/kg bw/day.","duration":"developmental","effect":"ive genes showed no change in response to BP-3. Reproductive toxicity The 2008 SCCP Opinion (SCCP/1201/08) noted that the studies provided as part of the dossier assessed in the earlier Opinion (SCCP/1069/06) had indicated that: ‘A teratogenicity study in rats showed BP-3 to be non-teratogenic under the conditions of the test. Only at the highest dosage level, which also caused maternal toxicity, some skeletal aberrations were noted. The NOAEL-value for maternal and developmental toxicity was 200 mg/kg bw/day. A NOAEL value of 400 mg/kg bw/day for reproductive toxicity was extracted from subchronic toxicity studies involving additional reproductive toxicity parameter measurements.’ A more recent NTP modified one-generation study found that gestation body weights of dams receiving 10,000 ppm BP-3 in the diet were slightly lower (~3%) than those of the control group and showed statistically significant differences. Dams receiving 3,000 or 10,000 ppm BP-3 in the diet displayed slight decreases in GD 6–21 body weight gain (~10%) r","endpoint":"repeated dose toxicity","ingredient":", and this warrants further","loael_value":"","noael_unit":"mg/kg bw/day","noael_value":"200","page":50,"route":"oral","species":"rat","study_id":"sccs_o_247_noael_015"}
UnifiedCodex:SCCS_SHADOW:beta.noael_studies	repeated dose toxicity	=100	mg/kg bw/day	rat	oral	Sub-chronic	repeated dose toxicity	SOURCE_SUBDIR=sccs_o_247; REPORT_TITLE=Final Opinion Scientific Committee on Consumer Safety SCCS OPINION on Benzophenone-3 (CAS No 131-57-7, EC No 205-031-5); OPINION_NUMBER=SCCS/1625/20; COMMITTEE=Scientific Committee on Consumer Safety (SCCS); REPORT_DATE=31 March 2021; VALUE_TEXT== 100; DOSE=at 3458 mg/kg bw/day In females: ↑ estrous cycle length in female rats at 3458 mg/kg bw/day based on effects in the kidney - 7 - Ref 7, 16, 33 in submission dossier Sub-chronic toxicity study OECD 408 Non GLP Rats Oral Food 0, 0, 0.02, 0.1, 0.5 and 1% in the diet ie ± 0, 20, 100, 500 and 1000 mg/kg bw/day 13 weeks In males and females: ↓ in abso...; EFFECT=at 3458 mg/kg bw/day In females: ↑ estrous cycle length in female rats at 3458 mg/kg bw/day based on effects in the kidney - 7 - Ref 7, 16, 33 in submission dossier Sub-chronic toxicity study OECD 408 Non GLP Rats Oral Food 0, 0, 0.02, 0.1, 0.5 and 1% in the diet ie ± 0, 20, 100, 500 and 1000 mg/kg bw/day 13 weeks In males and females: ↓ in absolute weights of adrenal gland, pituitary gland and gonads at 1000 mg/kg bw/day ↑ in relative thyroid and pituitary and adrenal weights at 500 and 1000 mg/kg bw/day NOAEL = 100 mg/kg bw/day; CITATION_NUMBERS=[]; DETAILS_JSON={"cas_number":"131-57-7","citation":"","dose":"at 3458 mg/kg bw/day In females: ↑ estrous cycle length in female rats at 3458 mg/kg bw/day based on effects in the kidney - 7 - Ref 7, 16, 33 in submission dossier Sub-chronic toxicity study OECD 408 Non GLP Rats Oral Food 0, 0, 0.02, 0.1, 0.5 and 1% in the diet ie ± 0, 20, 100, 500 and 1000 mg/kg bw/day 13 weeks In males and females: ↓ in abso...","duration":"Sub-chronic","effect":"at 3458 mg/kg bw/day In females: ↑ estrous cycle length in female rats at 3458 mg/kg bw/day based on effects in the kidney - 7 - Ref 7, 16, 33 in submission dossier Sub-chronic toxicity study OECD 408 Non GLP Rats Oral Food 0, 0, 0.02, 0.1, 0.5 and 1% in the diet ie ± 0, 20, 100, 500 and 1000 mg/kg bw/day 13 weeks In males and females: ↓ in absolute weights of adrenal gland, pituitary gland and gonads at 1000 mg/kg bw/day ↑ in relative thyroid and pituitary and adrenal weights at 500 and 1000 mg/kg bw/day NOAEL = 100 mg/kg bw/day","endpoint":"repeated dose toxicity","ingredient":", and this warrants further","loael_value":"","noael_unit":"mg/kg bw/day","noael_value":"= 100","page":66,"route":"oral","species":"rat","study_id":"sccs_o_247_noael_029"}
UnifiedCodex:SCCS_SHADOW:beta.noael_studies	repeated dose toxicity	=1246	mg/kg bw /day	rat	oral	Sub-chronic	repeated dose toxicity	SOURCE_SUBDIR=sccs_o_247; REPORT_TITLE=Final Opinion Scientific Committee on Consumer Safety SCCS OPINION on Benzophenone-3 (CAS No 131-57-7, EC No 205-031-5); OPINION_NUMBER=SCCS/1625/20; COMMITTEE=Scientific Committee on Consumer Safety (SCCS); REPORT_DATE=31 March 2021; VALUE_TEXT== 1246; DOSE=___________________________________________________________________________________________________ 67 - 8 - Ref 5, 7, 33 in submission dossier Sub-chronic toxicity study OECD 408 GLP Mice Oral Food 0, 3125,6250, 12500, 25000 and 50000 ppm , ie ± 0, 554, 1246, 2860, 6780 and 16238 mg/kg bw/day 13 weeks No effects on reproductive parameters at 67...; EFFECT=___________________________________________________________________________________________________ 67 - 8 - Ref 5, 7, 33 in submission dossier Sub-chronic toxicity study OECD 408 GLP Mice Oral Food 0, 3125,6250, 12500, 25000 and 50000 ppm , ie ± 0, 554, 1246, 2860, 6780 and 16238 mg/kg bw/day 13 weeks No effects on reproductive parameters at 6780 mg/kg bw/day or below Males: ↓ in sperm density and ↑ in abnormal sperm morphology at 16238 mg/kg bw/day Females: ↑ in estrous cycles length at 16238 mg/kg bw/day NOAEL = 1246 mg/kg bw /day based on systemic effects -9- Ref 21 Sub-chronic toxicity study GLP Rats 0 and 10000 ppm ie ± 585/632 mg/kg bw/day in males and females Estrogen- responsive genes showed no change in response to BP- 3 in transcriptome analysis -10- Ref 5, 7, 33 in submission dossier Sub-chronic toxicity study ± OECD 411 GLP Rats Dermal 0, 12.5, 25, 50, 100 and 200 mg/kg bw/day 13 weeks No effects on reproductive parameters NOAEL = 200 mg/kg bw/day -11- Mice Dermal 0, 22.8, 45.5, 91, ↓ in epi; CITATION_NUMBERS=[]; DETAILS_JSON={"cas_number":"131-57-7","citation":"","dose":"___________________________________________________________________________________________________ 67 - 8 - Ref 5, 7, 33 in submission dossier Sub-chronic toxicity study OECD 408 GLP Mice Oral Food 0, 3125,6250, 12500, 25000 and 50000 ppm , ie ± 0, 554, 1246, 2860, 6780 and 16238 mg/kg bw/day 13 weeks No effects on reproductive parameters at 67...","duration":"Sub-chronic","effect":"___________________________________________________________________________________________________ 67 - 8 - Ref 5, 7, 33 in submission dossier Sub-chronic toxicity study OECD 408 GLP Mice Oral Food 0, 3125,6250, 12500, 25000 and 50000 ppm , ie ± 0, 554, 1246, 2860, 6780 and 16238 mg/kg bw/day 13 weeks No effects on reproductive parameters at 6780 mg/kg bw/day or below Males: ↓ in sperm density and ↑ in abnormal sperm morphology at 16238 mg/kg bw/day Females: ↑ in estrous cycles length at 16238 mg/kg bw/day NOAEL = 1246 mg/kg bw /day based on systemic effects -9- Ref 21 Sub-chronic toxicity study GLP Rats 0 and 10000 ppm ie ± 585/632 mg/kg bw/day in males and females Estrogen- responsive genes showed no change in response to BP- 3 in transcriptome analysis -10- Ref 5, 7, 33 in submission dossier Sub-chronic toxicity study ± OECD 411 GLP Rats Dermal 0, 12.5, 25, 50, 100 and 200 mg/kg bw/day 13 weeks No effects on reproductive parameters NOAEL = 200 mg/kg bw/day -11- Mice Dermal 0, 22.8, 45.5, 91, ↓ in epi","endpoint":"repeated dose toxicity","ingredient":", and this warrants further","loael_value":"","noael_unit":"mg/kg bw /day","noael_value":"= 1246","page":67,"route":"oral","species":"rat","study_id":"sccs_o_247_noael_030"}
UnifiedCodex:SCCS_SHADOW:beta.noael_studies	repeated dose toxicity	=200	mg/kg bw/day	rat	dermal	Sub-chronic	repeated dose toxicity	SOURCE_SUBDIR=sccs_o_247; REPORT_TITLE=Final Opinion Scientific Committee on Consumer Safety SCCS OPINION on Benzophenone-3 (CAS No 131-57-7, EC No 205-031-5); OPINION_NUMBER=SCCS/1625/20; COMMITTEE=Scientific Committee on Consumer Safety (SCCS); REPORT_DATE=31 March 2021; VALUE_TEXT== 200; DOSE=kg bw/day Females: ↑ in estrous cycles length at 16238 mg/kg bw/day NOAEL = 1246 mg/kg bw /day based on systemic effects -9- Ref 21 Sub-chronic toxicity study GLP Rats 0 and 10000 ppm ie ± 585/632 mg/kg bw/day in males and females Estrogen- responsive genes showed no change in response to BP- 3 in transcriptome analysis -10- Ref 5, 7, 33 in subm...; EFFECT=kg bw/day Females: ↑ in estrous cycles length at 16238 mg/kg bw/day NOAEL = 1246 mg/kg bw /day based on systemic effects -9- Ref 21 Sub-chronic toxicity study GLP Rats 0 and 10000 ppm ie ± 585/632 mg/kg bw/day in males and females Estrogen- responsive genes showed no change in response to BP- 3 in transcriptome analysis -10- Ref 5, 7, 33 in submission dossier Sub-chronic toxicity study ± OECD 411 GLP Rats Dermal 0, 12.5, 25, 50, 100 and 200 mg/kg bw/day 13 weeks No effects on reproductive parameters NOAEL = 200 mg/kg bw/day -11- Mice Dermal 0, 22.8, 45.5, 91, ↓ in epididymal sperm density NOAEL = 364 mg/kg bw/day In view of the effects on sperm; CITATION_NUMBERS=[]; DETAILS_JSON={"cas_number":"131-57-7","citation":"","dose":"kg bw/day Females: ↑ in estrous cycles length at 16238 mg/kg bw/day NOAEL = 1246 mg/kg bw /day based on systemic effects -9- Ref 21 Sub-chronic toxicity study GLP Rats 0 and 10000 ppm ie ± 585/632 mg/kg bw/day in males and females Estrogen- responsive genes showed no change in response to BP- 3 in transcriptome analysis -10- Ref 5, 7, 33 in subm...","duration":"Sub-chronic","effect":"kg bw/day Females: ↑ in estrous cycles length at 16238 mg/kg bw/day NOAEL = 1246 mg/kg bw /day based on systemic effects -9- Ref 21 Sub-chronic toxicity study GLP Rats 0 and 10000 ppm ie ± 585/632 mg/kg bw/day in males and females Estrogen- responsive genes showed no change in response to BP- 3 in transcriptome analysis -10- Ref 5, 7, 33 in submission dossier Sub-chronic toxicity study ± OECD 411 GLP Rats Dermal 0, 12.5, 25, 50, 100 and 200 mg/kg bw/day 13 weeks No effects on reproductive parameters NOAEL = 200 mg/kg bw/day -11- Mice Dermal 0, 22.8, 45.5, 91, ↓ in epididymal sperm density NOAEL = 364 mg/kg bw/day In view of the effects on sperm","endpoint":"repeated dose toxicity","ingredient":", and this warrants further","loael_value":"","noael_unit":"mg/kg bw/day","noael_value":"= 200","page":67,"route":"dermal","species":"rat","study_id":"sccs_o_247_noael_031"}
UnifiedCodex:SCCS_SHADOW:beta.noael_studies	repeated dose toxicity	=364	mg/kg bw/day	rat	dermal	Sub-chronic	repeated dose toxicity	SOURCE_SUBDIR=sccs_o_247; REPORT_TITLE=Final Opinion Scientific Committee on Consumer Safety SCCS OPINION on Benzophenone-3 (CAS No 131-57-7, EC No 205-031-5); OPINION_NUMBER=SCCS/1625/20; COMMITTEE=Scientific Committee on Consumer Safety (SCCS); REPORT_DATE=31 March 2021; VALUE_TEXT== 364; DOSE=based on systemic effects -9- Ref 21 Sub-chronic toxicity study GLP Rats 0 and 10000 ppm ie ± 585/632 mg/kg bw/day in males and females Estrogen- responsive genes showed no change in response to BP- 3 in transcriptome analysis -10- Ref 5, 7, 33 in submission dossier Sub-chronic toxicity study ± OECD 411 GLP Rats Dermal 0, 12.5, 25, 50, 100 and 2...; EFFECT=based on systemic effects -9- Ref 21 Sub-chronic toxicity study GLP Rats 0 and 10000 ppm ie ± 585/632 mg/kg bw/day in males and females Estrogen- responsive genes showed no change in response to BP- 3 in transcriptome analysis -10- Ref 5, 7, 33 in submission dossier Sub-chronic toxicity study ± OECD 411 GLP Rats Dermal 0, 12.5, 25, 50, 100 and 200 mg/kg bw/day 13 weeks No effects on reproductive parameters NOAEL = 200 mg/kg bw/day -11- Mice Dermal 0, 22.8, 45.5, 91, ↓ in epididymal sperm density NOAEL = 364 mg/kg bw/day In view of the effects on sperm; CITATION_NUMBERS=[]; DETAILS_JSON={"cas_number":"131-57-7","citation":"","dose":"based on systemic effects -9- Ref 21 Sub-chronic toxicity study GLP Rats 0 and 10000 ppm ie ± 585/632 mg/kg bw/day in males and females Estrogen- responsive genes showed no change in response to BP- 3 in transcriptome analysis -10- Ref 5, 7, 33 in submission dossier Sub-chronic toxicity study ± OECD 411 GLP Rats Dermal 0, 12.5, 25, 50, 100 and 2...","duration":"Sub-chronic","effect":"based on systemic effects -9- Ref 21 Sub-chronic toxicity study GLP Rats 0 and 10000 ppm ie ± 585/632 mg/kg bw/day in males and females Estrogen- responsive genes showed no change in response to BP- 3 in transcriptome analysis -10- Ref 5, 7, 33 in submission dossier Sub-chronic toxicity study ± OECD 411 GLP Rats Dermal 0, 12.5, 25, 50, 100 and 200 mg/kg bw/day 13 weeks No effects on reproductive parameters NOAEL = 200 mg/kg bw/day -11- Mice Dermal 0, 22.8, 45.5, 91, ↓ in epididymal sperm density NOAEL = 364 mg/kg bw/day In view of the effects on sperm","endpoint":"repeated dose toxicity","ingredient":", and this warrants further","loael_value":"","noael_unit":"mg/kg bw/day","noael_value":"= 364","page":67,"route":"dermal","species":"rat","study_id":"sccs_o_247_noael_032"}
UnifiedCodex:SCCS_SHADOW:beta.noael_studies	repeated dose toxicity	1	%	rat	oral	Sub-chronic	repeated dose toxicity	SOURCE_SUBDIR=sccs_o_247; REPORT_TITLE=Final Opinion Scientific Committee on Consumer Safety SCCS OPINION on Benzophenone-3 (CAS No 131-57-7, EC No 205-031-5); OPINION_NUMBER=SCCS/1625/20; COMMITTEE=Scientific Committee on Consumer Safety (SCCS); REPORT_DATE=31 March 2021; VALUE_TEXT=1; DOSE=Unlabeled table on page 66: - 7 - Ref 7, 16, 33 in submission dossier Sub-chronic toxicity study OECD 408 Non GLP | Rats | Oral Food | 0, 0, 0.02, 0.1, 0.5 and 1% in the diet ie ± 0, 20, 100, 500 and 1000 mg/kg bw/day 13 weeks | In males and females: ↓ in absolute weights of adrenal gland, pituitary gland and gonads at 1000 mg/kg bw/day ↑ in rel...; EFFECT=Unlabeled table on page 66: - 7 - Ref 7, 16, 33 in submission dossier Sub-chronic toxicity study OECD 408 Non GLP | Rats | Oral Food | 0, 0, 0.02, 0.1, 0.5 and 1% in the diet ie ± 0, 20, 100, 500 and 1000 mg/kg bw/day 13 weeks | In males and females: ↓ in absolute weights of adrenal gland, pituitary gland and gonads at 1000 mg/kg bw/day ↑ in relative thyroid and pituitary and adrenal weights at 500 and 1000 mg/kg bw/day | NOAEL = 100 mg/kg bw/day; CITATION_NUMBERS=[]; DETAILS_JSON={"cas_number":"131-57-7","citation":"","dose":"Unlabeled table on page 66: - 7 - Ref 7, 16, 33 in submission dossier Sub-chronic toxicity study OECD 408 Non GLP | Rats | Oral Food | 0, 0, 0.02, 0.1, 0.5 and 1% in the diet ie ± 0, 20, 100, 500 and 1000 mg/kg bw/day 13 weeks | In males and females: ↓ in absolute weights of adrenal gland, pituitary gland and gonads at 1000 mg/kg bw/day ↑ in rel...","duration":"Sub-chronic","effect":"Unlabeled table on page 66: - 7 - Ref 7, 16, 33 in submission dossier Sub-chronic toxicity study OECD 408 Non GLP | Rats | Oral Food | 0, 0, 0.02, 0.1, 0.5 and 1% in the diet ie ± 0, 20, 100, 500 and 1000 mg/kg bw/day 13 weeks | In males and females: ↓ in absolute weights of adrenal gland, pituitary gland and gonads at 1000 mg/kg bw/day ↑ in relative thyroid and pituitary and adrenal weights at 500 and 1000 mg/kg bw/day | NOAEL = 100 mg/kg bw/day","endpoint":"repeated dose toxicity","ingredient":", and this warrants further","loael_value":"","noael_unit":"%","noael_value":"1","page":66,"route":"oral","species":"rat","study_id":"sccs_o_247_noael_050"}
UnifiedCodex:SCCS_SHADOW:beta.noael_studies	repeated dose toxicity	=100	mg/kg bw/day	rat	oral	Sub-chronic	repeated dose toxicity	SOURCE_SUBDIR=sccs_o_247; REPORT_TITLE=Final Opinion Scientific Committee on Consumer Safety SCCS OPINION on Benzophenone-3 (CAS No 131-57-7, EC No 205-031-5); OPINION_NUMBER=SCCS/1625/20; COMMITTEE=Scientific Committee on Consumer Safety (SCCS); REPORT_DATE=31 March 2021; VALUE_TEXT== 100; DOSE=Unlabeled table on page 66: - 7 - Ref 7, 16, 33 in submission dossier Sub-chronic toxicity study OECD 408 Non GLP | Rats | Oral Food | 0, 0, 0.02, 0.1, 0.5 and 1% in the diet ie ± 0, 20, 100, 500 and 1000 mg/kg bw/day 13 weeks | In males and females: ↓ in absolute weights of adrenal gland, pituitary gland and gonads at 1000 mg/kg bw/day ↑ in rel...; EFFECT=Unlabeled table on page 66: - 7 - Ref 7, 16, 33 in submission dossier Sub-chronic toxicity study OECD 408 Non GLP | Rats | Oral Food | 0, 0, 0.02, 0.1, 0.5 and 1% in the diet ie ± 0, 20, 100, 500 and 1000 mg/kg bw/day 13 weeks | In males and females: ↓ in absolute weights of adrenal gland, pituitary gland and gonads at 1000 mg/kg bw/day ↑ in relative thyroid and pituitary and adrenal weights at 500 and 1000 mg/kg bw/day | NOAEL = 100 mg/kg bw/day; CITATION_NUMBERS=[]; DETAILS_JSON={"cas_number":"131-57-7","citation":"","dose":"Unlabeled table on page 66: - 7 - Ref 7, 16, 33 in submission dossier Sub-chronic toxicity study OECD 408 Non GLP | Rats | Oral Food | 0, 0, 0.02, 0.1, 0.5 and 1% in the diet ie ± 0, 20, 100, 500 and 1000 mg/kg bw/day 13 weeks | In males and females: ↓ in absolute weights of adrenal gland, pituitary gland and gonads at 1000 mg/kg bw/day ↑ in rel...","duration":"Sub-chronic","effect":"Unlabeled table on page 66: - 7 - Ref 7, 16, 33 in submission dossier Sub-chronic toxicity study OECD 408 Non GLP | Rats | Oral Food | 0, 0, 0.02, 0.1, 0.5 and 1% in the diet ie ± 0, 20, 100, 500 and 1000 mg/kg bw/day 13 weeks | In males and females: ↓ in absolute weights of adrenal gland, pituitary gland and gonads at 1000 mg/kg bw/day ↑ in relative thyroid and pituitary and adrenal weights at 500 and 1000 mg/kg bw/day | NOAEL = 100 mg/kg bw/day","endpoint":"repeated dose toxicity","ingredient":", and this warrants further","loael_value":"","noael_unit":"mg/kg bw/day","noael_value":"= 100","page":66,"route":"oral","species":"rat","study_id":"sccs_o_247_noael_051"}
UnifiedCodex:SCCS_SHADOW:beta.noael_studies	repeated dose toxicity	50000	ppm	mouse	oral	Sub-chronic	repeated dose toxicity	SOURCE_SUBDIR=sccs_o_247; REPORT_TITLE=Final Opinion Scientific Committee on Consumer Safety SCCS OPINION on Benzophenone-3 (CAS No 131-57-7, EC No 205-031-5); OPINION_NUMBER=SCCS/1625/20; COMMITTEE=Scientific Committee on Consumer Safety (SCCS); REPORT_DATE=31 March 2021; VALUE_TEXT=50000; DOSE=Unlabeled table on page 67: - 8 - Ref 5, 7, 33 in submission dossier Sub-chronic toxicity study OECD 408 GLP | Mice | Oral Food | 0, 3125,6250, 12500, 25000 and 50000 ppm , ie ± 0, 554, 1246, 2860, 6780 and 16238 mg/kg bw/day 13 weeks | No effects on reproductive parameters at 6780 mg/kg bw/day or below | Males: ↓ in sperm density and ↑ in abnor...; EFFECT=Unlabeled table on page 67: - 8 - Ref 5, 7, 33 in submission dossier Sub-chronic toxicity study OECD 408 GLP | Mice | Oral Food | 0, 3125,6250, 12500, 25000 and 50000 ppm , ie ± 0, 554, 1246, 2860, 6780 and 16238 mg/kg bw/day 13 weeks | No effects on reproductive parameters at 6780 mg/kg bw/day or below | Males: ↓ in sperm density and ↑ in abnormal sperm morphology at 16238 mg/kg bw/day Females: ↑ in estrous cycles length at 16238 mg/kg bw/day | NOAEL = 1246 mg/kg bw /day based on systemic effects; CITATION_NUMBERS=[]; DETAILS_JSON={"cas_number":"131-57-7","citation":"","dose":"Unlabeled table on page 67: - 8 - Ref 5, 7, 33 in submission dossier Sub-chronic toxicity study OECD 408 GLP | Mice | Oral Food | 0, 3125,6250, 12500, 25000 and 50000 ppm , ie ± 0, 554, 1246, 2860, 6780 and 16238 mg/kg bw/day 13 weeks | No effects on reproductive parameters at 6780 mg/kg bw/day or below | Males: ↓ in sperm density and ↑ in abnor...","duration":"Sub-chronic","effect":"Unlabeled table on page 67: - 8 - Ref 5, 7, 33 in submission dossier Sub-chronic toxicity study OECD 408 GLP | Mice | Oral Food | 0, 3125,6250, 12500, 25000 and 50000 ppm , ie ± 0, 554, 1246, 2860, 6780 and 16238 mg/kg bw/day 13 weeks | No effects on reproductive parameters at 6780 mg/kg bw/day or below | Males: ↓ in sperm density and ↑ in abnormal sperm morphology at 16238 mg/kg bw/day Females: ↑ in estrous cycles length at 16238 mg/kg bw/day | NOAEL = 1246 mg/kg bw /day based on systemic effects","endpoint":"repeated dose toxicity","ingredient":", and this warrants further","loael_value":"","noael_unit":"ppm","noael_value":"50000","page":67,"route":"oral","species":"mouse","study_id":"sccs_o_247_noael_052"}
UnifiedCodex:SCCS_SHADOW:beta.noael_studies	repeated dose toxicity	200	mg/kg bw/day	rat	dermal	Sub-chronic	repeated dose toxicity	SOURCE_SUBDIR=sccs_o_247; REPORT_TITLE=Final Opinion Scientific Committee on Consumer Safety SCCS OPINION on Benzophenone-3 (CAS No 131-57-7, EC No 205-031-5); OPINION_NUMBER=SCCS/1625/20; COMMITTEE=Scientific Committee on Consumer Safety (SCCS); REPORT_DATE=31 March 2021; VALUE_TEXT=200; DOSE=Unlabeled table on page 67: -10- Ref 5, 7, 33 in submission dossier Sub-chronic toxicity study ± OECD 411 GLP | Rats | Dermal | 0, 12.5, 25, 50, 100 and 200 mg/kg bw/day 13 weeks | No effects on reproductive parameters | NOAEL = 200 mg/kg bw/day; EFFECT=Unlabeled table on page 67: -10- Ref 5, 7, 33 in submission dossier Sub-chronic toxicity study ± OECD 411 GLP | Rats | Dermal | 0, 12.5, 25, 50, 100 and 200 mg/kg bw/day 13 weeks | No effects on reproductive parameters | NOAEL = 200 mg/kg bw/day; CITATION_NUMBERS=[]; DETAILS_JSON={"cas_number":"131-57-7","citation":"","dose":"Unlabeled table on page 67: -10- Ref 5, 7, 33 in submission dossier Sub-chronic toxicity study ± OECD 411 GLP | Rats | Dermal | 0, 12.5, 25, 50, 100 and 200 mg/kg bw/day 13 weeks | No effects on reproductive parameters | NOAEL = 200 mg/kg bw/day","duration":"Sub-chronic","effect":"Unlabeled table on page 67: -10- Ref 5, 7, 33 in submission dossier Sub-chronic toxicity study ± OECD 411 GLP | Rats | Dermal | 0, 12.5, 25, 50, 100 and 200 mg/kg bw/day 13 weeks | No effects on reproductive parameters | NOAEL = 200 mg/kg bw/day","endpoint":"repeated dose toxicity","ingredient":", and this warrants further","loael_value":"","noael_unit":"mg/kg bw/day","noael_value":"200","page":67,"route":"dermal","species":"rat","study_id":"sccs_o_247_noael_053"}
UnifiedCodex:SCCS_SHADOW:beta.noael_studies	repeated dose toxicity	=200	mg/kg bw/day	rat	dermal	Sub-chronic	repeated dose toxicity	SOURCE_SUBDIR=sccs_o_247; REPORT_TITLE=Final Opinion Scientific Committee on Consumer Safety SCCS OPINION on Benzophenone-3 (CAS No 131-57-7, EC No 205-031-5); OPINION_NUMBER=SCCS/1625/20; COMMITTEE=Scientific Committee on Consumer Safety (SCCS); REPORT_DATE=31 March 2021; VALUE_TEXT== 200; DOSE=Unlabeled table on page 67: -10- Ref 5, 7, 33 in submission dossier Sub-chronic toxicity study ± OECD 411 GLP | Rats | Dermal | 0, 12.5, 25, 50, 100 and 200 mg/kg bw/day 13 weeks | No effects on reproductive parameters | NOAEL = 200 mg/kg bw/day; EFFECT=Unlabeled table on page 67: -10- Ref 5, 7, 33 in submission dossier Sub-chronic toxicity study ± OECD 411 GLP | Rats | Dermal | 0, 12.5, 25, 50, 100 and 200 mg/kg bw/day 13 weeks | No effects on reproductive parameters | NOAEL = 200 mg/kg bw/day; CITATION_NUMBERS=[]; DETAILS_JSON={"cas_number":"131-57-7","citation":"","dose":"Unlabeled table on page 67: -10- Ref 5, 7, 33 in submission dossier Sub-chronic toxicity study ± OECD 411 GLP | Rats | Dermal | 0, 12.5, 25, 50, 100 and 200 mg/kg bw/day 13 weeks | No effects on reproductive parameters | NOAEL = 200 mg/kg bw/day","duration":"Sub-chronic","effect":"Unlabeled table on page 67: -10- Ref 5, 7, 33 in submission dossier Sub-chronic toxicity study ± OECD 411 GLP | Rats | Dermal | 0, 12.5, 25, 50, 100 and 200 mg/kg bw/day 13 weeks | No effects on reproductive parameters | NOAEL = 200 mg/kg bw/day","endpoint":"repeated dose toxicity","ingredient":", and this warrants further","loael_value":"","noael_unit":"mg/kg bw/day","noael_value":"= 200","page":67,"route":"dermal","species":"rat","study_id":"sccs_o_247_noael_055"}
UnifiedCodex:SCCS_SHADOW:beta.noael_studies	reproductive toxicity	=828	mg/kg bw/day	rat	oral	-	reproductive toxicity	SOURCE_SUBDIR=sccp_o_078; REPORT_TITLE=OPINION ON BENZOPHENONE-3 COLIPA N° S38; OPINION_NUMBER=SCCP/1069/06; COMMITTEE=SCCP; REPORT_DATE=19 December 2006; VALUE_TEXT== 828; DOSE=204 mg/kg bw/day: no deviations among the reproductive parameters studied 828 mg/kg bw/day: no deviations among the reproductive parameters studied 3,458 mg/kg bw/day: males: decreased right caudal, testicular and epididymal weights; decreased sperm number per caudal tissue females : prolonged cycle length.; EFFECT=ssue weight. Observations in the females included vaginal cytology examinations and estrual cyclicity. The following effects were noted (dietary levels were converted to dosages): 204 mg/kg bw/day: no deviations among the reproductive parameters studied 828 mg/kg bw/day: no deviations among the reproductive parameters studied 3,458 mg/kg bw/day: males: decreased right caudal, testicular and epididymal weights; decreased sperm number per caudal tissue females : prolonged cycle length. Study authors' conclusion: NOAEL (reproduction) = 828 mg/kg bw/day for male and female rats. Ref.: 24, 30; CITATION=Ref.: 24, 30; CITATION_NUMBERS=[24,30]; REFERENCE=Ref.: 24, 30; DETAILS_JSON={"cas_number":"131-57-7","citation":"Ref.: 24, 30","dose":"204 mg/kg bw/day: no deviations among the reproductive parameters studied 828 mg/kg bw/day: no deviations among the reproductive parameters studied 3,458 mg/kg bw/day: males: decreased right caudal, testicular and epididymal weights; decreased sperm number per caudal tissue females : prolonged cycle length.","duration":"","effect":"ssue weight. Observations in the females included vaginal cytology examinations and estrual cyclicity. The following effects were noted (dietary levels were converted to dosages): 204 mg/kg bw/day: no deviations among the reproductive parameters studied 828 mg/kg bw/day: no deviations among the reproductive parameters studied 3,458 mg/kg bw/day: males: decreased right caudal, testicular and epididymal weights; decreased sperm number per caudal tissue females : prolonged cycle length. Study authors' conclusion: NOAEL (reproduction) = 828 mg/kg bw/day for male and female rats. Ref.: 24, 30","endpoint":"reproductive toxicity","ingredient":"INCI name","loael_value":"","noael_unit":"mg/kg bw/day","noael_value":"= 828","page":21,"route":"oral","species":"rat","study_id":"sccp_o_078_noael_012"}
UnifiedCodex:SCCS_SHADOW:beta.noael_studies	reproductive toxicity	=2860	mg/kg bw/day	mouse	oral	-	reproductive toxicity	SOURCE_SUBDIR=sccp_o_078; REPORT_TITLE=OPINION ON BENZOPHENONE-3 COLIPA N° S38; OPINION_NUMBER=SCCP/1069/06; COMMITTEE=SCCP; REPORT_DATE=19 December 2006; VALUE_TEXT== 2,860; DOSE=554 mg/kg bw/day: no deviations among the reproductive parameters studied 2,860 mg/kg bw/day: no deviations among the reproductive parameters studied 16,238 mg/kg bw/day: decreased sperm number per caudal tissue and increased incidence of abnormal sperm in the males Study authors' conclusion:; EFFECT=d morphology and sperm number per caudal tissue weight. Observations in the females included vaginal cytology examinations and estrual cyclicity. The following effects were noted (dietary levels were converted to dosages): 554 mg/kg bw/day: no deviations among the reproductive parameters studied 2,860 mg/kg bw/day: no deviations among the reproductive parameters studied 16,238 mg/kg bw/day: decreased sperm number per caudal tissue and increased incidence of abnormal sperm in the males Study authors' conclusion: NOAEL (reproduction) = 2,860 mg/kg bw/day for male and female mice. Ref.: 24, 30 Reproductive Assessment by Continuous Breeding (RACB) in the mouse (1991) The "Continuous Breeding Protocol" is a test design used by the US National Toxicology Program. It consists of four related tasks (see figure below), which are not all necessarily performed for every compound tested. TASK 4 Offspring assessment F1 generation (Control + 1 dosed group) TASK 3 Determination of affected sex (F0 generation) TASK 4 Offspring assessment F; CITATION=Ref.: 24, 30 Reproductive Assessment by Continuous Breeding (RACB) in the mouse (1991) The "Continuous Breeding Protocol" is a test design used by the US National Toxicology Program; CITATION_NUMBERS=[24,30,1991]; REFERENCE=Ref.: 24, 30 Reproductive Assessment by Continuous Breeding (RACB) in the mouse (1991) The "Continuous Breeding Protocol" is a test design used by the US National Toxicology Program; DETAILS_JSON={"cas_number":"131-57-7","citation":"Ref.: 24, 30 Reproductive Assessment by Continuous Breeding (RACB) in the mouse (1991) The \"Continuous Breeding Protocol\" is a test design used by the US National Toxicology Program","dose":"554 mg/kg bw/day: no deviations among the reproductive parameters studied 2,860 mg/kg bw/day: no deviations among the reproductive parameters studied 16,238 mg/kg bw/day: decreased sperm number per caudal tissue and increased incidence of abnormal sperm in the males Study authors' conclusion:","duration":"","effect":"d morphology and sperm number per caudal tissue weight. Observations in the females included vaginal cytology examinations and estrual cyclicity. The following effects were noted (dietary levels were converted to dosages): 554 mg/kg bw/day: no deviations among the reproductive parameters studied 2,860 mg/kg bw/day: no deviations among the reproductive parameters studied 16,238 mg/kg bw/day: decreased sperm number per caudal tissue and increased incidence of abnormal sperm in the males Study authors' conclusion: NOAEL (reproduction) = 2,860 mg/kg bw/day for male and female mice. Ref.: 24, 30 Reproductive Assessment by Continuous Breeding (RACB) in the mouse (1991) The \"Continuous Breeding Protocol\" is a test design used by the US National Toxicology Program. It consists of four related tasks (see figure below), which are not all necessarily performed for every compound tested. TASK 4 Offspring assessment F1 generation (Control + 1 dosed group) TASK 3 Determination of affected sex (F0 generation) TASK 4 Offspring assessment F","endpoint":"reproductive toxicity","ingredient":"INCI name","loael_value":"","noael_unit":"mg/kg bw/day","noael_value":"= 2,860","page":22,"route":"oral","species":"mouse","study_id":"sccp_o_078_noael_013"}
UnifiedCodex:SCCS_SHADOW:beta.noael_studies	reproductive toxicity	9500	mg/kg bw/day	mouse	dermal	20-day	reproductive toxicity	SOURCE_SUBDIR=sccp_o_078; REPORT_TITLE=OPINION ON BENZOPHENONE-3 COLIPA N° S38; OPINION_NUMBER=SCCP/1069/06; COMMITTEE=SCCP; REPORT_DATE=19 December 2006; VALUE_TEXT=9500; DOSE=5 dams died unexpectedly during the Task 2 20-day period 3,950 mg/kg bw/day: reduced number of pups / litter; reduced dam weights;; EFFECT=ation, necropsy was performed, organs were weighed and preserved for histopathology (especially reproductive organs). The following effects were noted: 1,850 mg/kg bw/day: 5 dams died unexpectedly during the Task 2 20-day period 3,950 mg/kg bw/day: reduced number of pups / litter; reduced dam weights; 4 dams died unexpectedly during the Task 2 20-day period 9,050mg/kg bw/day: reduced number of pups / litter; reduced dam weights; 9 dams died unexpectedly during the Task 2 20-day period Study authors' conclusion: NOAEL (fertility) = 8600/9500 mg/kg bw/day for male/female mice. Ref.: 9, 31 B. Dermal reproduction toxicity screening tests A short communication published in 1993 describes the assessment of the reproductive toxic potential of Benzophenone-3 in male B6C3F1 mice after a 13-week repeated dermal application of dosages of 0, 20, 100 and 400 mg/kg bw/day. Reproductive organ weights, cauda epididymal sperm concentration, proportion of motile and abnormal sperm and testicular spermatid concentration were determined and tes; CITATION=Ref.: 9, 31 B; CITATION_NUMBERS=[9,31]; REFERENCE=Ref.: 9, 31 B; DETAILS_JSON={"cas_number":"131-57-7","citation":"Ref.: 9, 31 B","dose":"5 dams died unexpectedly during the Task 2 20-day period 3,950 mg/kg bw/day: reduced number of pups / litter; reduced dam weights;","duration":"20-day","effect":"ation, necropsy was performed, organs were weighed and preserved for histopathology (especially reproductive organs). The following effects were noted: 1,850 mg/kg bw/day: 5 dams died unexpectedly during the Task 2 20-day period 3,950 mg/kg bw/day: reduced number of pups / litter; reduced dam weights; 4 dams died unexpectedly during the Task 2 20-day period 9,050mg/kg bw/day: reduced number of pups / litter; reduced dam weights; 9 dams died unexpectedly during the Task 2 20-day period Study authors' conclusion: NOAEL (fertility) = 8600/9500 mg/kg bw/day for male/female mice. Ref.: 9, 31 B. Dermal reproduction toxicity screening tests A short communication published in 1993 describes the assessment of the reproductive toxic potential of Benzophenone-3 in male B6C3F1 mice after a 13-week repeated dermal application of dosages of 0, 20, 100 and 400 mg/kg bw/day. Reproductive organ weights, cauda epididymal sperm concentration, proportion of motile and abnormal sperm and testicular spermatid concentration were determined and tes","endpoint":"reproductive toxicity","ingredient":"INCI name","loael_value":"","noael_unit":"mg/kg bw/day","noael_value":"9500","page":23,"route":"dermal","species":"mouse","study_id":"sccp_o_078_noael_014"}
UnifiedCodex:SCCS_SHADOW:beta.noael_studies	reproductive toxicity	200	mg/kg bw/day	rat	oral	-	reproductive toxicity	SOURCE_SUBDIR=sccp_o_078; REPORT_TITLE=OPINION ON BENZOPHENONE-3 COLIPA N° S38; OPINION_NUMBER=SCCP/1069/06; COMMITTEE=SCCP; REPORT_DATE=19 December 2006; VALUE_TEXT=200; DOSE=Therefore the NOAEL for the investigated reproductive effects in male and female rats and mice was in each case considered the highest dose level applied, more specifically 200 mg/kg bw/day for the rat and 364 mg/kg bw/day for the mouse.; EFFECT=SCCP/1069/06 OPINION ON BENZOPHENONE-3 24 since there was no other effect on reproductive organs in the study, neither in the other selective reproductive parameters, weight of the reproductive organs nor histopathological examination. Therefore the NOAEL for the investigated reproductive effects in male and female rats and mice was in each case considered the highest dose level applied, more specifically 200 mg/kg bw/day for the rat and 364 mg/kg bw/day for the mouse. Ref.: 30 3.3.8.2. Teratogenicity - rat - oral Date of study: 01-16 November 2004 Guideline/method: Annex V to Dir. 67/548/EEC, Method B.31; OECD Guideline 414 Species/strain: Crl : WI(Han) Wistar rat Group size: 25 mated females per dosage group Test substance: Benzophenone-3 Batch: 101 Purity: 99.; CITATION=Ref.: 30 3; CITATION_NUMBERS=[30,3]; REFERENCE=Ref.: 30 3; DETAILS_JSON={"cas_number":"131-57-7","citation":"Ref.: 30 3","dose":"Therefore the NOAEL for the investigated reproductive effects in male and female rats and mice was in each case considered the highest dose level applied, more specifically 200 mg/kg bw/day for the rat and 364 mg/kg bw/day for the mouse.","duration":"","effect":"SCCP/1069/06 OPINION ON BENZOPHENONE-3 24 since there was no other effect on reproductive organs in the study, neither in the other selective reproductive parameters, weight of the reproductive organs nor histopathological examination. Therefore the NOAEL for the investigated reproductive effects in male and female rats and mice was in each case considered the highest dose level applied, more specifically 200 mg/kg bw/day for the rat and 364 mg/kg bw/day for the mouse. Ref.: 30 3.3.8.2. Teratogenicity - rat - oral Date of study: 01-16 November 2004 Guideline/method: Annex V to Dir. 67/548/EEC, Method B.31; OECD Guideline 414 Species/strain: Crl : WI(Han) Wistar rat Group size: 25 mated females per dosage group Test substance: Benzophenone-3 Batch: 101 Purity: 99.","endpoint":"reproductive toxicity","ingredient":"INCI name","loael_value":"","noael_unit":"mg/kg bw/day","noael_value":"200","page":24,"route":"oral","species":"rat","study_id":"sccp_o_078_noael_016"}
UnifiedCodex:SCCS_SHADOW:beta.noael_studies	reproductive toxicity	9500	mg/kg bw/day	mouse	-	developmental	reproductive toxicity	SOURCE_SUBDIR=sccp_o_078; REPORT_TITLE=OPINION ON BENZOPHENONE-3 COLIPA N° S38; OPINION_NUMBER=SCCP/1069/06; COMMITTEE=SCCP; REPORT_DATE=19 December 2006; VALUE_TEXT=9500; DOSE=SCCP/1069/06 OPINION ON BENZOPHENONE-3 25 3.3.8.3 Overall conclusion of the submission authors on reproductive toxicity Benzophenone-3 was shown to have no effect on fertility when tested up to very high dose levels within a RACB (Reproductive Assessment by Continuous Breeding) study in mice.; EFFECT=SCCP/1069/06 OPINION ON BENZOPHENONE-3 25 3.3.8.3 Overall conclusion of the submission authors on reproductive toxicity Benzophenone-3 was shown to have no effect on fertility when tested up to very high dose levels within a RACB (Reproductive Assessment by Continuous Breeding) study in mice. The NOAEL for fertility was the highest investigated dosage level of 8600/9500 mg/kg bw/day in male/female mice. Within this study the reproductive performance was affected in the form of a slightly lower number of live pups at birth. Signs of developmental toxicity consisted of impaired body weight/body weight gain of the pups. However, in any case these effects were only noted at a dosage level with overt parental toxicity. Consequently, the NOAEL for systemic, reproductive and developmental toxicity was 1800/1900 mg/kg b; CITATION_NUMBERS=[]; DETAILS_JSON={"cas_number":"131-57-7","citation":"","dose":"SCCP/1069/06 OPINION ON BENZOPHENONE-3 25 3.3.8.3 Overall conclusion of the submission authors on reproductive toxicity Benzophenone-3 was shown to have no effect on fertility when tested up to very high dose levels within a RACB (Reproductive Assessment by Continuous Breeding) study in mice.","duration":"developmental","effect":"SCCP/1069/06 OPINION ON BENZOPHENONE-3 25 3.3.8.3 Overall conclusion of the submission authors on reproductive toxicity Benzophenone-3 was shown to have no effect on fertility when tested up to very high dose levels within a RACB (Reproductive Assessment by Continuous Breeding) study in mice. The NOAEL for fertility was the highest investigated dosage level of 8600/9500 mg/kg bw/day in male/female mice. Within this study the reproductive performance was affected in the form of a slightly lower number of live pups at birth. Signs of developmental toxicity consisted of impaired body weight/body weight gain of the pups. However, in any case these effects were only noted at a dosage level with overt parental toxicity. Consequently, the NOAEL for systemic, reproductive and developmental toxicity was 1800/1900 mg/kg b","endpoint":"reproductive toxicity","ingredient":"INCI name","loael_value":"","noael_unit":"mg/kg bw/day","noael_value":"9500","page":25,"route":"","species":"mouse","study_id":"sccp_o_078_noael_018"}
UnifiedCodex:SCCS_SHADOW:beta.noael_studies	reproductive toxicity	1900	mg/kg bw/day	rat	oral	developmental	reproductive toxicity	SOURCE_SUBDIR=sccp_o_078; REPORT_TITLE=OPINION ON BENZOPHENONE-3 COLIPA N° S38; OPINION_NUMBER=SCCP/1069/06; COMMITTEE=SCCP; REPORT_DATE=19 December 2006; VALUE_TEXT=1900; DOSE=The NOAEL for fertility was the highest investigated dosage level of 8600/9500 mg/kg bw/day in male/female mice.; EFFECT=a RACB (Reproductive Assessment by Continuous Breeding) study in mice. The NOAEL for fertility was the highest investigated dosage level of 8600/9500 mg/kg bw/day in male/female mice. Within this study the reproductive performance was affected in the form of a slightly lower number of live pups at birth. Signs of developmental toxicity consisted of impaired body weight/body weight gain of the pups. However, in any case these effects were only noted at a dosage level with overt parental toxicity. Consequently, the NOAEL for systemic, reproductive and developmental toxicity was 1800/1900 mg/kg bw/day in males/females. Repeated oral application of Benzophenone-3 for 13 weeks to rats and mice caused only slight effects in selective parameters accompanied with overt systemic toxicity at the highest investigated dosage levels of 3656/3261 mg/kg bw/day in male/female rats and 13937/18539 mg/kg bw/day in male/female mice). In rats, the epididymal sperm count was reduced and a decreased absolute cauda, epididymal and testis weight as a; CITATION_NUMBERS=[]; DETAILS_JSON={"cas_number":"131-57-7","citation":"","dose":"The NOAEL for fertility was the highest investigated dosage level of 8600/9500 mg/kg bw/day in male/female mice.","duration":"developmental","effect":"a RACB (Reproductive Assessment by Continuous Breeding) study in mice. The NOAEL for fertility was the highest investigated dosage level of 8600/9500 mg/kg bw/day in male/female mice. Within this study the reproductive performance was affected in the form of a slightly lower number of live pups at birth. Signs of developmental toxicity consisted of impaired body weight/body weight gain of the pups. However, in any case these effects were only noted at a dosage level with overt parental toxicity. Consequently, the NOAEL for systemic, reproductive and developmental toxicity was 1800/1900 mg/kg bw/day in males/females. Repeated oral application of Benzophenone-3 for 13 weeks to rats and mice caused only slight effects in selective parameters accompanied with overt systemic toxicity at the highest investigated dosage levels of 3656/3261 mg/kg bw/day in male/female rats and 13937/18539 mg/kg bw/day in male/female mice). In rats, the epididymal sperm count was reduced and a decreased absolute cauda, epididymal and testis weight as a","endpoint":"reproductive toxicity","ingredient":"INCI name","loael_value":"","noael_unit":"mg/kg bw/day","noael_value":"1900","page":25,"route":"oral","species":"rat","study_id":"sccp_o_078_noael_019"}
UnifiedCodex:SCCS_SHADOW:beta.noael_studies	reproductive toxicity	200	mg/kg bw/d	rat	dermal	prenatal	reproductive toxicity	SOURCE_SUBDIR=sccp_o_078; REPORT_TITLE=OPINION ON BENZOPHENONE-3 COLIPA N° S38; OPINION_NUMBER=SCCP/1069/06; COMMITTEE=SCCP; REPORT_DATE=19 December 2006; VALUE_TEXT=200; DOSE=mice of another strain for the same period led to no signs of reproductive toxicity up to the slightly higher dose level of 400 mg/kg bw/d.; EFFECT=mice of another strain for the same period led to no signs of reproductive toxicity up to the slightly higher dose level of 400 mg/kg bw/d. Thus, the reported effect on the sperm count was finally considered as incidental. A recent prenatal developmental toxicity study performed according to valid test guideline and under GLP conditions with characterized test material resulted in marginal effect on few components of the skeleton was at the high dose level in association with overt maternal toxicity, the achieved NOAEL was 200 mg/kg bw/d for maternal and prenatal developmental toxicity. 3.3.9. Toxicokinetics In a study published in 1986, the disposition of Benzophenone-3 in rats dosed orally, intravenously and topically, has been investigated. [14C]Benzophenone-3 was administered orally at dosages of 3, 28, 293 and 2570 mg/kg, dermally at approximate dosages of 0.2, 0.6, 0.8 and 3.2 mg/kg and intravenously at a dosage of 4.6 mg/kg. The dermal dosage of 0.6 mg/kg involved the use of a sunscreen lotion as vehicle, while the othe; CITATION_NUMBERS=[]; DETAILS_JSON={"cas_number":"131-57-7","citation":"","dose":"mice of another strain for the same period led to no signs of reproductive toxicity up to the slightly higher dose level of 400 mg/kg bw/d.","duration":"prenatal","effect":"mice of another strain for the same period led to no signs of reproductive toxicity up to the slightly higher dose level of 400 mg/kg bw/d. Thus, the reported effect on the sperm count was finally considered as incidental. A recent prenatal developmental toxicity study performed according to valid test guideline and under GLP conditions with characterized test material resulted in marginal effect on few components of the skeleton was at the high dose level in association with overt maternal toxicity, the achieved NOAEL was 200 mg/kg bw/d for maternal and prenatal developmental toxicity. 3.3.9. Toxicokinetics In a study published in 1986, the disposition of Benzophenone-3 in rats dosed orally, intravenously and topically, has been investigated. [14C]Benzophenone-3 was administered orally at dosages of 3, 28, 293 and 2570 mg/kg, dermally at approximate dosages of 0.2, 0.6, 0.8 and 3.2 mg/kg and intravenously at a dosage of 4.6 mg/kg. The dermal dosage of 0.6 mg/kg involved the use of a sunscreen lotion as vehicle, while the othe","endpoint":"reproductive toxicity","ingredient":"INCI name","loael_value":"","noael_unit":"mg/kg bw/d","noael_value":"200","page":25,"route":"dermal","species":"rat","study_id":"sccp_o_078_noael_022"}
UnifiedCodex:SCCS_SHADOW:beta.noael_studies	reproductive toxicity	9500	mg/kg bw/day	-	-	-	reproductive toxicity	SOURCE_SUBDIR=sccp_o_078; REPORT_TITLE=OPINION ON BENZOPHENONE-3 COLIPA N° S38; OPINION_NUMBER=SCCP/1069/06; COMMITTEE=SCCP; REPORT_DATE=19 December 2006; VALUE_TEXT=9500; DOSE=NOAEL (fertility) = 8600/9500 mg/kg bw/day for male/female; EFFECT=Unlabeled table on page 23: Study authors' conclusion: NOAEL (fertility) = 8600/9500 mg/kg bw/day for male/female; CITATION_NUMBERS=[]; DETAILS_JSON={"cas_number":"131-57-7","citation":"","dose":"NOAEL (fertility) = 8600/9500 mg/kg bw/day for male/female","duration":"","effect":"Unlabeled table on page 23: Study authors' conclusion: NOAEL (fertility) = 8600/9500 mg/kg bw/day for male/female","endpoint":"reproductive toxicity","ingredient":"INCI name","loael_value":"","noael_unit":"mg/kg bw/day","noael_value":"9500","page":23,"route":"","species":"","study_id":"sccp_o_078_noael_064"}
UnifiedCodex:SCCS_SHADOW:beta.noael_studies	reproductive toxicity	24	-	-	-	-	reproductive toxicity	SOURCE_SUBDIR=sccp_o_078; REPORT_TITLE=OPINION ON BENZOPHENONE-3 COLIPA N° S38; OPINION_NUMBER=SCCP/1069/06; COMMITTEE=SCCP; REPORT_DATE=19 December 2006; VALUE_TEXT=unclear:Unlabeled table on page 24: examination. Therefore the NOAEL for the investigated reproductive effects in male and; EFFECT=Unlabeled table on page 24: examination. Therefore the NOAEL for the investigated reproductive effects in male and; CITATION_NUMBERS=[]; DETAILS_JSON={"cas_number":"131-57-7","citation":"","dose":"","duration":"","effect":"Unlabeled table on page 24: examination. Therefore the NOAEL for the investigated reproductive effects in male and","endpoint":"reproductive toxicity","ingredient":"INCI name","loael_value":"","noael_unit":"","noael_value":"unclear:Unlabeled table on page 24: examination. Therefore the NOAEL for the investigated reproductive effects in male and","page":24,"route":"","species":"","study_id":"sccp_o_078_noael_067"}
UnifiedCodex:SCCS_SHADOW:beta.noael_studies	reproductive toxicity	9500	mg/kg bw/day	-	-	-	reproductive toxicity	SOURCE_SUBDIR=sccp_o_078; REPORT_TITLE=OPINION ON BENZOPHENONE-3 COLIPA N° S38; OPINION_NUMBER=SCCP/1069/06; COMMITTEE=SCCP; REPORT_DATE=19 December 2006; VALUE_TEXT=9500; DOSE=NOAEL for fertility was the highest investigated dosage level of 8600/9500 mg/kg bw/day in; EFFECT=Unlabeled table on page 25: NOAEL for fertility was the highest investigated dosage level of 8600/9500 mg/kg bw/day in; CITATION_NUMBERS=[]; DETAILS_JSON={"cas_number":"131-57-7","citation":"","dose":"NOAEL for fertility was the highest investigated dosage level of 8600/9500 mg/kg bw/day in","duration":"","effect":"Unlabeled table on page 25: NOAEL for fertility was the highest investigated dosage level of 8600/9500 mg/kg bw/day in","endpoint":"reproductive toxicity","ingredient":"INCI name","loael_value":"","noael_unit":"mg/kg bw/day","noael_value":"9500","page":25,"route":"","species":"","study_id":"sccp_o_078_noael_075"}
UnifiedCodex:SCCS_SHADOW:beta.noael_studies	reproductive toxicity	25	-	-	-	-	reproductive toxicity	SOURCE_SUBDIR=sccp_o_078; REPORT_TITLE=OPINION ON BENZOPHENONE-3 COLIPA N° S38; OPINION_NUMBER=SCCP/1069/06; COMMITTEE=SCCP; REPORT_DATE=19 December 2006; VALUE_TEXT=unclear:Unlabeled table on page 25: a clear NOAEL for the investigated reproductive parameters.; EFFECT=Unlabeled table on page 25: a clear NOAEL for the investigated reproductive parameters.; CITATION_NUMBERS=[]; DETAILS_JSON={"cas_number":"131-57-7","citation":"","dose":"","duration":"","effect":"Unlabeled table on page 25: a clear NOAEL for the investigated reproductive parameters.","endpoint":"reproductive toxicity","ingredient":"INCI name","loael_value":"","noael_unit":"","noael_value":"unclear:Unlabeled table on page 25: a clear NOAEL for the investigated reproductive parameters.","page":25,"route":"","species":"","study_id":"sccp_o_078_noael_077"}
UnifiedCodex:SCCS_SHADOW:beta.noael_studies	reproductive toxicity	200	mg/kg bw/day	-	-	-	reproductive toxicity	SOURCE_SUBDIR=sccp_o_159; REPORT_TITLE=OPINION ON Benzophenone-3 COLIPA n° S38; OPINION_NUMBER=SCCP/1201/08; COMMITTEE=Scientific Committee on Consumer Products (SCCP); REPORT_DATE=16 December 2008; VALUE_TEXT=200; DOSE=Unlabeled table on page 7: toxicity was 200 mg/kg bw/day.; EFFECT=Unlabeled table on page 7: toxicity was 200 mg/kg bw/day. A NOAEL value of 400 mg/kg bw/day for reproductive; CITATION_NUMBERS=[]; DETAILS_JSON={"cas_number":"131-57-7","citation":"","dose":"Unlabeled table on page 7: toxicity was 200 mg/kg bw/day.","duration":"","effect":"Unlabeled table on page 7: toxicity was 200 mg/kg bw/day. A NOAEL value of 400 mg/kg bw/day for reproductive","endpoint":"reproductive toxicity","ingredient":"2-hydroxy-4-methoxybenzophenone was submitted by COLIPA1 in December 2005.","loael_value":"","noael_unit":"mg/kg bw/day","noael_value":"200","page":7,"route":"","species":"","study_id":"sccp_o_159_noael_012"}
UnifiedCodex:SCCS_SHADOW:beta.noael_studies	reproductive toxicity	200	mg/kg bw/day	rat	-	Chronic	reproductive toxicity	SOURCE_SUBDIR=sccs_o_247; REPORT_TITLE=Final Opinion Scientific Committee on Consumer Safety SCCS OPINION on Benzophenone-3 (CAS No 131-57-7, EC No 205-031-5); OPINION_NUMBER=SCCS/1625/20; COMMITTEE=Scientific Committee on Consumer Safety (SCCS); REPORT_DATE=31 March 2021; VALUE_TEXT=200; DOSE=study male rat livers from the 10,000 ppm and control groups.; EFFECT=study male rat livers from the 10,000 ppm and control groups. The observed effects on transcription were consistent with a mild induction of xenobiotic metabolism-related processes that is likely related to the observed relative liver weight increase. Analysis of a subset of estrogen-responsive genes showed no change in response to BP-3. 3.4.4.3 Chronic (> 12 months) toxicity / 3.4.5 Reproductive toxicity The 2008 SCCP Opinion (SCCP/1201/08) noted that ‘the available teratogenicity study in the rat generated a NOAEL-value for maternal and developmental toxicity of 200 mg/kg bw/day, which was used to calculate the MoS ‘. The NOAEL value is derived from a 2005 prenatal developmental toxicity study (https://echa.europa.eu/el/registration-dossier/-/registered- dossier/5515/7/9/3). Other reprotoxicity studies have been published since the release of the previous SCCS opinion. The more informative studies are described below and summarised in Annex-1. The study from Nakamura et al. (2015) brings information of the reprotoxicity of; CITATION_NUMBERS=[]; DETAILS_JSON={"cas_number":"131-57-7","citation":"","dose":"study male rat livers from the 10,000 ppm and control groups.","duration":"Chronic","effect":"study male rat livers from the 10,000 ppm and control groups. The observed effects on transcription were consistent with a mild induction of xenobiotic metabolism-related processes that is likely related to the observed relative liver weight increase. Analysis of a subset of estrogen-responsive genes showed no change in response to BP-3. 3.4.4.3 Chronic (> 12 months) toxicity / 3.4.5 Reproductive toxicity The 2008 SCCP Opinion (SCCP/1201/08) noted that ‘the available teratogenicity study in the rat generated a NOAEL-value for maternal and developmental toxicity of 200 mg/kg bw/day, which was used to calculate the MoS ‘. The NOAEL value is derived from a 2005 prenatal developmental toxicity study (https://echa.europa.eu/el/registration-dossier/-/registered- dossier/5515/7/9/3). Other reprotoxicity studies have been published since the release of the previous SCCS opinion. The more informative studies are described below and summarised in Annex-1. The study from Nakamura et al. (2015) brings information of the reprotoxicity of","endpoint":"reproductive toxicity","ingredient":", and this warrants further","loael_value":"","noael_unit":"mg/kg bw/day","noael_value":"200","page":26,"route":"","species":"rat","study_id":"sccs_o_247_noael_003"}
UnifiedCodex:SCCS_SHADOW:beta.noael_studies	reproductive toxicity	200	mg/kg bw/day	rat	-	Chronic	reproductive toxicity	SOURCE_SUBDIR=sccs_o_247; REPORT_TITLE=Final Opinion Scientific Committee on Consumer Safety SCCS OPINION on Benzophenone-3 (CAS No 131-57-7, EC No 205-031-5); OPINION_NUMBER=SCCS/1625/20; COMMITTEE=Scientific Committee on Consumer Safety (SCCS); REPORT_DATE=31 March 2021; VALUE_TEXT=200; DOSE=3.4.4.3 Chronic (> 12 months) toxicity / 3.4.5 Reproductive toxicity The 2008 SCCP Opinion (SCCP/1201/08) noted that ‘the available teratogenicity study in the rat generated a NOAEL-value for maternal and developmental toxicity of 200 mg/kg bw/day, which was used to calculate the MoS ‘.; EFFECT=with a mild induction of xenobiotic metabolism-related processes that is likely related to the observed relative liver weight increase. Analysis of a subset of estrogen-responsive genes showed no change in response to BP-3. 3.4.4.3 Chronic (> 12 months) toxicity / 3.4.5 Reproductive toxicity The 2008 SCCP Opinion (SCCP/1201/08) noted that ‘the available teratogenicity study in the rat generated a NOAEL-value for maternal and developmental toxicity of 200 mg/kg bw/day, which was used to calculate the MoS ‘. The NOAEL value is derived from a 2005 prenatal developmental toxicity study (https://echa.europa.eu/el/registration-dossier/-/registered- dossier/5515/7/9/3). Other reprotoxicity studies have been published since the release of the previous SCCS opinion. The more informative studies are described below and summarised in Annex-1. The study from Nakamura et al. (2015) brings information of the reprotoxicity of BP-3 and also on some ED properties. This study is therefore described in this section and also in more detail in th; CITATION_NUMBERS=[]; DETAILS_JSON={"cas_number":"131-57-7","citation":"","dose":"3.4.4.3 Chronic (> 12 months) toxicity / 3.4.5 Reproductive toxicity The 2008 SCCP Opinion (SCCP/1201/08) noted that ‘the available teratogenicity study in the rat generated a NOAEL-value for maternal and developmental toxicity of 200 mg/kg bw/day, which was used to calculate the MoS ‘.","duration":"Chronic","effect":"with a mild induction of xenobiotic metabolism-related processes that is likely related to the observed relative liver weight increase. Analysis of a subset of estrogen-responsive genes showed no change in response to BP-3. 3.4.4.3 Chronic (> 12 months) toxicity / 3.4.5 Reproductive toxicity The 2008 SCCP Opinion (SCCP/1201/08) noted that ‘the available teratogenicity study in the rat generated a NOAEL-value for maternal and developmental toxicity of 200 mg/kg bw/day, which was used to calculate the MoS ‘. The NOAEL value is derived from a 2005 prenatal developmental toxicity study (https://echa.europa.eu/el/registration-dossier/-/registered- dossier/5515/7/9/3). Other reprotoxicity studies have been published since the release of the previous SCCS opinion. The more informative studies are described below and summarised in Annex-1. The study from Nakamura et al. (2015) brings information of the reprotoxicity of BP-3 and also on some ED properties. This study is therefore described in this section and also in more detail in th","endpoint":"reproductive toxicity","ingredient":", and this warrants further","loael_value":"","noael_unit":"mg/kg bw/day","noael_value":"200","page":26,"route":"","species":"rat","study_id":"sccs_o_247_noael_004"}
UnifiedCodex:SCCS_SHADOW:beta.noael_studies	reproductive toxicity	1000	ppm	rat	dermal	-	reproductive toxicity	SOURCE_SUBDIR=sccs_o_247; REPORT_TITLE=Final Opinion Scientific Committee on Consumer Safety SCCS OPINION on Benzophenone-3 (CAS No 131-57-7, EC No 205-031-5); OPINION_NUMBER=SCCS/1625/20; COMMITTEE=Scientific Committee on Consumer Safety (SCCS); REPORT_DATE=31 March 2021; VALUE_TEXT=1000; DOSE=Due to the effects on the spermatocytes, which may be due to an ED effects of BP-3, the SCCS considered 3000 ppm as a LOAEL and 1000 ppm as the NOAEL (67.9 mg /kg bw/day) Safety evaluation (including calculation of the MoS) The SCCS has a dermal absorption of 9.9% [mean (3.1%) + 2 SD (2*3.4%)] for the use of BP-3 as a UV filter at 6% for the cal...; LOAEL_VALUE=67.9 mg /kg bw/day; EFFECT=igh doses that can only be considered far beyond the human exposure range. The study from Nakamura et al. (2015) that determined the effects of maternal and lactational exposure to BP-3 on development and reproductive organs of offspring of time-mated female Harlan Sprague-Dawley rats has been selected by the SCCS as the key study to be used for the calculation of the MoS. Due to the effects on the spermatocytes, which may be due to an ED effects of BP-3, the SCCS considered 3000 ppm as a LOAEL and 1000 ppm as the NOAEL (67.9 mg /kg bw/day) Safety evaluation (including calculation of the MoS) The SCCS has a dermal absorption of 9.9% [mean (3.1%) + 2 SD (2*3.4%)] for the use of BP-3 as a UV filter at 6% for the calculation of the systemic exposure dose (SED) and the margin of safety (MoS) for sunscreen products. For other cosmetic products, the SCCS has used a dermal absorption of 8% [mean (4%) + 2 SD (2*2%)]. For the calculation of the margin of safety (MoS), the SCCS has used a NOAEL of 67.9 mg/kg bw/d from the Nakamura et al.; CITATION_NUMBERS=[]; DETAILS_JSON={"cas_number":"131-57-7","citation":"","dose":"Due to the effects on the spermatocytes, which may be due to an ED effects of BP-3, the SCCS considered 3000 ppm as a LOAEL and 1000 ppm as the NOAEL (67.9 mg /kg bw/day) Safety evaluation (including calculation of the MoS) The SCCS has a dermal absorption of 9.9% [mean (3.1%) + 2 SD (2*3.4%)] for the use of BP-3 as a UV filter at 6% for the cal...","duration":"","effect":"igh doses that can only be considered far beyond the human exposure range. The study from Nakamura et al. (2015) that determined the effects of maternal and lactational exposure to BP-3 on development and reproductive organs of offspring of time-mated female Harlan Sprague-Dawley rats has been selected by the SCCS as the key study to be used for the calculation of the MoS. Due to the effects on the spermatocytes, which may be due to an ED effects of BP-3, the SCCS considered 3000 ppm as a LOAEL and 1000 ppm as the NOAEL (67.9 mg /kg bw/day) Safety evaluation (including calculation of the MoS) The SCCS has a dermal absorption of 9.9% [mean (3.1%) + 2 SD (2*3.4%)] for the use of BP-3 as a UV filter at 6% for the calculation of the systemic exposure dose (SED) and the margin of safety (MoS) for sunscreen products. For other cosmetic products, the SCCS has used a dermal absorption of 8% [mean (4%) + 2 SD (2*2%)]. For the calculation of the margin of safety (MoS), the SCCS has used a NOAEL of 67.9 mg/kg bw/d from the Nakamura et al.","endpoint":"reproductive toxicity","ingredient":", and this warrants further","loael_value":"67.9 mg /kg bw/day","noael_unit":"ppm","noael_value":"1000","page":51,"route":"dermal","species":"rat","study_id":"sccs_o_247_noael_016"}
UnifiedCodex:SCCS_SHADOW:beta.noael_studies	reproductive toxicity	0	ppm	-	-	-	reproductive toxicity	SOURCE_SUBDIR=sccs_o_247; REPORT_TITLE=Final Opinion Scientific Committee on Consumer Safety SCCS OPINION on Benzophenone-3 (CAS No 131-57-7, EC No 205-031-5); OPINION_NUMBER=SCCS/1625/20; COMMITTEE=Scientific Committee on Consumer Safety (SCCS); REPORT_DATE=31 March 2021; VALUE_TEXT=000; DOSE=i.e. around 67.9, 207.1, 670.8, 1798.3, 7-8 ↓ body weights of dams at 50 000 ppm at GD 10, 15 and 20; and at 25 000 ppm at GD15 ↓ organ (liver, kidney) weights (absolute no significant difference in the number of implantation sites/litter, mean resorptions/litt er, % litters with resorptions, number and weights of live One foetus with hydrocepha...; LOAEL_VALUE=1798 mg/kg/d; EFFECT=i.e. around 67.9, 207.1, 670.8, 1798.3, 7-8 ↓ body weights of dams at 50 000 ppm at GD 10, 15 and 20; and at 25 000 ppm at GD15 ↓ organ (liver, kidney) weights (absolute no significant difference in the number of implantation sites/litter, mean resorptions/litt er, % litters with resorptions, number and weights of live One foetus with hydrocephaly at 50 000 ppm but no other malformations observed In male offspring at PND23: ↓ AGD in male at 50 000 ppm ↓ spermatocytes per seminiferous tubules at 3000 ppm and higher NOAEL : 3 000 ppm (670 mg/kg bw/day LOAEL : 10 000 ppm (1798 mg/kg/d) It would have been useful to have measured foetal testosterone as it is known that a decrease during specific windows of sensitivity in male foetuses mat impaired the development of reproductive; CITATION_NUMBERS=[]; DETAILS_JSON={"cas_number":"131-57-7","citation":"","dose":"i.e. around 67.9, 207.1, 670.8, 1798.3, 7-8 ↓ body weights of dams at 50 000 ppm at GD 10, 15 and 20; and at 25 000 ppm at GD15 ↓ organ (liver, kidney) weights (absolute no significant difference in the number of implantation sites/litter, mean resorptions/litt er, % litters with resorptions, number and weights of live One foetus with hydrocepha...","duration":"","effect":"i.e. around 67.9, 207.1, 670.8, 1798.3, 7-8 ↓ body weights of dams at 50 000 ppm at GD 10, 15 and 20; and at 25 000 ppm at GD15 ↓ organ (liver, kidney) weights (absolute no significant difference in the number of implantation sites/litter, mean resorptions/litt er, % litters with resorptions, number and weights of live One foetus with hydrocephaly at 50 000 ppm but no other malformations observed In male offspring at PND23: ↓ AGD in male at 50 000 ppm ↓ spermatocytes per seminiferous tubules at 3000 ppm and higher NOAEL : 3 000 ppm (670 mg/kg bw/day LOAEL : 10 000 ppm (1798 mg/kg/d) It would have been useful to have measured foetal testosterone as it is known that a decrease during specific windows of sensitivity in male foetuses mat impaired the development of reproductive","endpoint":"reproductive toxicity","ingredient":", and this warrants further","loael_value":"1798 mg/kg/d","noael_unit":"ppm","noael_value":"000","page":62,"route":"","species":"","study_id":"sccs_o_247_noael_021"}
UnifiedCodex:SCCS_SHADOW:beta.noael_studies	reproductive toxicity	0	ppm	rat	-	-	reproductive toxicity	SOURCE_SUBDIR=sccs_o_247; REPORT_TITLE=Final Opinion Scientific Committee on Consumer Safety SCCS OPINION on Benzophenone-3 (CAS No 131-57-7, EC No 205-031-5); OPINION_NUMBER=SCCS/1625/20; COMMITTEE=Scientific Committee on Consumer Safety (SCCS); REPORT_DATE=31 March 2021; VALUE_TEXT=000; DOSE=35- 51 Study period: | Rat Sprague- Dawley | Food | , 0, 1000, 3000, 10 000, 25 000, 50 000 ppm, i.e. around 67.9, 207.1, 670.8, 1798.3, | 7-8 | ↓ body weights of dams at 50 000 ppm at GD 10, 15 and 20; and at 25 000 ppm at GD15 ↓ organ (liver, kidney) weights (absolute | no significant difference in the number of implantation sites/litter, mean...; LOAEL_VALUE=1798 mg/kg/d; EFFECT=Unlabeled table on page 62: - 2 - Nakamura et al. 2015 Birth Defects Res 104: 35- 51 Study period: | Rat Sprague- Dawley | Food | , 0, 1000, 3000, 10 000, 25 000, 50 000 ppm, i.e. around 67.9, 207.1, 670.8, 1798.3, | 7-8 | ↓ body weights of dams at 50 000 ppm at GD 10, 15 and 20; and at 25 000 ppm at GD15 ↓ organ (liver, kidney) weights (absolute | no significant difference in the number of implantation sites/litter, mean resorptions/litt er, % litters with resorptions, number and weights of live | One foetus with hydrocephaly at 50 000 ppm but no other malformations observed | In male offspring at PND23: ↓ AGD in male at 50 000 ppm ↓ spermatocytes per seminiferous tubules at 3000 ppm and higher | NOAEL : 3 000 ppm (670 mg/kg bw/day LOAEL : 10 000 ppm (1798 mg/kg/d) | It would have been useful to have measured foetal testosterone as it is known that a decrease during specific windows of sensitivity in male foetuses mat impaired the development of reproductive; CITATION_NUMBERS=[]; DETAILS_JSON={"cas_number":"131-57-7","citation":"","dose":"35- 51 Study period: | Rat Sprague- Dawley | Food | , 0, 1000, 3000, 10 000, 25 000, 50 000 ppm, i.e. around 67.9, 207.1, 670.8, 1798.3, | 7-8 | ↓ body weights of dams at 50 000 ppm at GD 10, 15 and 20; and at 25 000 ppm at GD15 ↓ organ (liver, kidney) weights (absolute | no significant difference in the number of implantation sites/litter, mean...","duration":"","effect":"Unlabeled table on page 62: - 2 - Nakamura et al. 2015 Birth Defects Res 104: 35- 51 Study period: | Rat Sprague- Dawley | Food | , 0, 1000, 3000, 10 000, 25 000, 50 000 ppm, i.e. around 67.9, 207.1, 670.8, 1798.3, | 7-8 | ↓ body weights of dams at 50 000 ppm at GD 10, 15 and 20; and at 25 000 ppm at GD15 ↓ organ (liver, kidney) weights (absolute | no significant difference in the number of implantation sites/litter, mean resorptions/litt er, % litters with resorptions, number and weights of live | One foetus with hydrocephaly at 50 000 ppm but no other malformations observed | In male offspring at PND23: ↓ AGD in male at 50 000 ppm ↓ spermatocytes per seminiferous tubules at 3000 ppm and higher | NOAEL : 3 000 ppm (670 mg/kg bw/day LOAEL : 10 000 ppm (1798 mg/kg/d) | It would have been useful to have measured foetal testosterone as it is known that a decrease during specific windows of sensitivity in male foetuses mat impaired the development of reproductive","endpoint":"reproductive toxicity","ingredient":", and this warrants further","loael_value":"1798 mg/kg/d","noael_unit":"ppm","noael_value":"000","page":62,"route":"","species":"rat","study_id":"sccs_o_247_noael_043"}

openFDA substances 4 endpoints

Source	Endpoint Type	Value	Unit	Species	Route	Duration	Study Type	Reference
openFDA substances	FDA UNII substance identifier	95OOS7VE0Y	UNII	-	-	-	chemical	{"approval_status":null,"molecular_formula":"C14H12O3","source_table":"substance_identifiers_fda","substance_class":"chemical","unii_code":"95OOS7VE0Y"}
openFDA substances	FDA UNII substance identifier	95OOS7VE0Y	UNII	-	-	-	chemical	{"approval_status":null,"molecular_formula":"C14H12O3","source_table":"substance_identifiers_fda","substance_class":"chemical","unii_code":"95OOS7VE0Y"}
openFDA substances	FDA UNII substance identifier	95OOS7VE0Y	UNII	-	-	-	chemical	{"approval_status":null,"molecular_formula":"C14H12O3","source_table":"substance_identifiers_fda","substance_class":"chemical","unii_code":"95OOS7VE0Y"}
openFDA substances	FDA UNII substance identifier	95OOS7VE0Y	UNII	-	-	-	chemical	{"approval_status":null,"molecular_formula":"C14H12O3","source_table":"substance_identifiers_fda","substance_class":"chemical","unii_code":"95OOS7VE0Y"}