NOAEL Studies Cosmetic Ingredient

CI 77947 (Zinc Oxide) NOAEL Studies

INCI: CI 77947

CAS: 1314-13-2

Raw No Observed Adverse Effect Level endpoint records grouped by source. This page does not render calculated Margin of Safety values.

COSMOS_DB 10 endpoints
Source Endpoint Type Value Unit Species Route Duration Study Type Reference
COSMOS_DB NOAEL 606 mg/kg bw/day rat oral 10 day Special Toxicology Study US FDA CFSAN PAFA; US FDA CFSAN PAFA Study
COSMOS_DB NOAEL 600 mg/kg bw/day rat oral 21 day Short Term Toxicity US FDA CFSAN PAFA; US FDA CFSAN PAFA Study
COSMOS_DB NOAEL 500 mg/kg bw/day rat oral 28 day Short Term Toxicity US FDA CFSAN PAFA; US FDA CFSAN PAFA Study
COSMOS_DB NOAEL 400 mg/kg bw/day rat oral 56 day Short Term Toxicity US FDA CFSAN PAFA; US FDA CFSAN PAFA Study
COSMOS_DB NOAEL 172 mg/kg bw/day rat oral 252 day Chronic US FDA CFSAN PAFA; US FDA CFSAN PAFA Study
COSMOS_DB NOAEL 99 mg/kg bw/day sheep oral 70 day Short Term Toxicity US FDA CFSAN PAFA; US FDA CFSAN PAFA Study
COSMOS_DB NOAEL 149 mg/kg bw/day cattle oral 4 day Special Toxicology Study US FDA CFSAN PAFA; US FDA CFSAN PAFA Study
COSMOS_DB NOAEL 45 mg/kg bw/day swine oral 14 day Short Term Toxicity US FDA CFSAN PAFA; US FDA CFSAN PAFA Study
COSMOS_DB NOAEL 100 mg/kg bw/day swine oral 14 day Short Term Toxicity US FDA CFSAN PAFA; US FDA CFSAN PAFA Study
COSMOS_DB NOAEL 164 mg/kg bw/day swine oral 28 day Short Term Toxicity US FDA CFSAN PAFA; US FDA CFSAN PAFA Study
NTP_ICE_acute_inhalation 2 endpoints
Source Endpoint Type Value Unit Species Route Duration Study Type Reference
NTP_ICE_acute_inhalation LC50 >5.7 mg/L - Inhalation Duration=4 hr In Vivo; AcuteInhalNICEATM; Rat Acute Inhalation Toxicity sheet=Data; excel_row=4202; Record_ID=acute_inhalation_1839; Data_Type=In Vivo; Internal_Data_Source=AcuteInhalNICEATM; Mixture=Chemical; DTXSID=DTXSID7035016; Assay=Rat Acute Inhalation Toxicity; Endpoint=LC50; Response_Modifier=>; Response=5.7; Response_Unit=mg/L; Reference=REACH; URL=https://echa.europa.eu/registration-dossier/-/registered-dossier/16139/7/3/3/?documentUUID=f0900b38-089f-4db8-a4a5-d11deef9b233; URL_CompTox=https://comptox.epa.gov/dashboard/chemical/details/DTXSID7035016
NTP_ICE_acute_inhalation LC50 >1.79 mg/L - Inhalation Duration=4 hr In Vivo; AcuteInhalNICEATM; Rat Acute Inhalation Toxicity sheet=Data; excel_row=4203; Record_ID=acute_inhalation_1832; Data_Type=In Vivo; Internal_Data_Source=AcuteInhalNICEATM; Mixture=Chemical; DTXSID=DTXSID7035016; Assay=Rat Acute Inhalation Toxicity; Endpoint=LC50; Response_Modifier=>; Response=1.79; Response_Unit=mg/L; Reference=REACH; URL=https://echa.europa.eu/registration-dossier/-/registered-dossier/16139/7/3/3/?documentUUID=d5093ff7-b3f3-4595-8fb5-707d8303b2e3; URL_CompTox=https://comptox.epa.gov/dashboard/chemical/details/DTXSID7035016
SCCNFP_vision_codex 20 endpoints
Source Endpoint Type Value Unit Species Route Duration Study Type Reference
SCCNFP_vision_codex NOAEL =3000 ppm rat - - NOAEL study {"dose":"e and cholesterol were reduced and alkaline phosphatase and urea nitrogen were increased in high dose animals.","effect":"e and cholesterol were reduced and alkaline phosphatase and urea nitrogen were increased in high dose animals. High dose females showed reduced ALAT and increased calcium levels, ASAT was increased in high dose males. Absolute and relative thyroid weights of males and kidney weights of females were increased at the highest dose. Gross pathology and histopathology showed changes in kidneys, thyroids, pancreas (degeneration/necrosis of acinar cells, clarification of nucleoli), gastrointestinal tract, and spleen. The NOEL for mice in this study was found at the mid dose at 3000 ppm (about 470 mg ZnSO4.7 H2O/kg bw (104 mg Zn2+/kg bw). Wistar rats : at the high dose level a moderate reduction in leucocyte counts, slightly decreased hematocrit and haemoglobin values (males only) and decreased total protein and cholesterol values were recorded. Absolute and relative liver weights and relative kidney weights were decreased in high dose males. Histopathology showed pancreatic damage (degeneration, necrosis of acinar cells, clarification","page":7,"pdf":"out222_en.pdf","row_type":"noael_study","study_id":"out222_en_noael_001"}
SCCNFP_vision_codex NOAEL =0.5 mg/kg/day human oral 6 weeks NOAEL study {"citation":"Ref. : 14 Human studies Since zinc is an essential trace element for all mammalian species, its presence in the diet of humans and animals as well as in drinking water is required","dose":"In this regard, the mammalian organism is used to handle varying quantities of externally administered zinc, such that Zn2+ homeostasis is regulated via control mechanisms of absorption and excretion.","effect":"2+/kg bw). Ref. : 14 Human studies Since zinc is an essential trace element for all mammalian species, its presence in the diet of humans and animals as well as in drinking water is required. In this regard, the mammalian organism is used to handle varying quantities of externally administered zinc, such that Zn2+ homeostasis is regulated via control mechanisms of absorption and excretion. In humans, the average daily intake is estimated at about 15 mg of Zn2+. The available evidence from human studies points to a NOEL of about 0.5 mg/kg/day and thus confirms the safe exposure level, which could be predicted from the animal data. A series of human experimental studies have been published which report adverse effects from oral administration of zinc salts : * 47 healthy volunteers ingested ZnSO4 tablets three times a day for 6 weeks, resulting in a total daily dose of 2 mg Zn2+/kg bw. Headaches, nausea, vomiting, loss of appetite and abdominal cramps were seen in 26 of the volunteers. Ref. : 15 * Oral doses of 160 mg ZnSO4/day (2","page":7,"pdf":"out222_en.pdf","row_type":"noael_study","study_id":"out222_en_noael_003"}
SCCNFP_vision_codex NOAEL =42.5 mg/kg rabbit oral developmental developmental toxicity {"citation":"Ref. : 27 Species : Female Dutch rabbits Number of animals : 14-19 animals per group Test substance : ZnSO4 (unspecified) 6-amino-nicotinamide (positive control) Doses : ZnSO4 : 0, 0","dose":"Results No compound-related effects were observed at any dose level.","effect":"a lutea, implantations, viable foetuses and resorptions. All foetuses were weighed, sexed and examined for gross external defects. In addition, skeletal examinations (in two-thirds of the foetuses) and soft tissue examinations (in the remaining one-third of foetuses) were performed. Results No compound-related effects were observed at any dose level. In particular, there was no indication of any specific teratogenic activity of ZnSO4 under the conditions of this experiment. Conclusion The No Observed Effect Level (NOEL) with regard to maternal and developmental toxicity of ZnSO4 was 42.5 mg/kg (corresponding to about 17 mg/kg if expressed as zinc). Ref. : 27 Species : Female Dutch rabbits Number of animals : 14-19 animals per group Test substance : ZnSO4 (unspecified) 6-amino-nicotinamide (positive control) Doses : ZnSO4 : 0, 0.6, 2.8, 13.0 and 60.0 mg/kg by gavage in water 6-amino-nicotinamide : 2.5 mg/kg by gavage Exposure period : ZnSO4: day 6-18 of gestation (p.c.) 6-amino-nicotinamide: single application at day 19 of gestat","page":13,"pdf":"out222_en.pdf","row_type":"noael_study","study_id":"out222_en_noael_004"}
SCCNFP_vision_codex NOAEL =60 mg/kg rat oral developmental developmental toxicity {"citation":"Ref. : 28 Species : Female Sprague Dawley: CFE rats Number of animals : 10 animals per group Test substance : ZnO Doses and exposure period 7 groups received the test substance at levels","dose":"Zinc oxide ____________________________________________________________________________________________ 14 Conclusion The No Observed Effect Level (NOEL) with regard to maternal and developmental toxicity of Zinc Sulfate was at least 60.0 mg/kg (corresponding to about 24 mg/kg if expressed as zinc).","effect":"SCCNFP/0649/03, final Evaluation and opinion on : Zinc oxide ____________________________________________________________________________________________ 14 Conclusion The No Observed Effect Level (NOEL) with regard to maternal and developmental toxicity of Zinc Sulfate was at least 60.0 mg/kg (corresponding to about 24 mg/kg if expressed as zinc). Ref. : 28 Species : Female Sprague Dawley: CFE rats Number of animals : 10 animals per group Test substance : ZnO Doses and exposure period 7 groups received the test substance at levels of 2000 (about 100 mg/kg/d) or 4000 ppm (about 200 mg/kg/day) in the diet. 7 equally sized control groups received the basal diet without test substance. 4 groups were fed the test die","page":14,"pdf":"out222_en.pdf","row_type":"noael_study","study_id":"out222_en_noael_005"}
SCCNFP_vision_codex NOAEL =40 % human oral developmental developmental toxicity {"citation":"Ref. : 29 2","dose":"Conclusion ZnO, 2000 ppm, administered from day 21 prior to mating until day 15 of gestation induced no adverse effects on foetal development.","effect":"e observed in foetal whole body samples. These analytical results support the interpretation that the observed developmental effects of exaggerated high zinc doses are mediated by depletion of certain essential minerals such as copper. Conclusion ZnO, 2000 ppm, administered from day 21 prior to mating until day 15 of gestation induced no adverse effects on foetal development. This dietary level corresponds to a daily dose of about 100 mg/kg expressed as ZnO, or about 80 mg/kg expressed as zinc which represents the NOEL in this study. Ref. : 29 2.7. Toxicokinetics (incl. Percutaneous Absorption) Method : In vivo, human Volunteers: : 6 healthy males Test substance : ZnO Site of application : Chest, upper and lower legs Exposure : Daily application of 40% ZnO in ointment for a of period 10 days","page":14,"pdf":"out222_en.pdf","row_type":"noael_study","study_id":"out222_en_noael_006"}
SCCNFP_vision_codex NOAEL =3000 ppm rat - - NOAEL study {"dose":"e and cholesterol were reduced and alkaline phosphatase and urea nitrogen were increased in high dose animals.","effect":"e and cholesterol were reduced and alkaline phosphatase and urea nitrogen were increased in high dose animals. High dose females showed reduced ALAT and increased calcium levels, ASAT was increased in high dose males. Absolute and relative thyroid weights of males and kidney weights of females were increased at the highest dose. Gross pathology and histopathology showed changes in kidneys, thyroids, pancreas (degeneration/necrosis of acinar cells, clarification of nucleoli), gastrointestinal tract, and spleen. The NOEL for mice in this study was found at the mid dose at 3000 ppm (about 470 mg ZnSO4.7 H2O/kg bw (104 mg Zn2+/kg bw). Wistar rats : at the high dose level a moderate reduction in leucocyte counts, slightly decreased hematocrit and haemoglobin values (males only) and decreased total protein and cholesterol values were recorded. Absolute and relative liver weights and relative kidney weights were decreased in high dose males. Histopathology showed pancreatic damage (degeneration, necrosis of acinar cells, clarification","page":7,"pdf":"out222_en.pdf","row_type":"noael_study","study_id":"out222_en_noael_001"}
SCCNFP_vision_codex NOAEL =0.5 mg/kg/day human oral 6 weeks NOAEL study {"citation":"Ref. : 14 Human studies Since zinc is an essential trace element for all mammalian species, its presence in the diet of humans and animals as well as in drinking water is required","dose":"In this regard, the mammalian organism is used to handle varying quantities of externally administered zinc, such that Zn2+ homeostasis is regulated via control mechanisms of absorption and excretion.","effect":"2+/kg bw). Ref. : 14 Human studies Since zinc is an essential trace element for all mammalian species, its presence in the diet of humans and animals as well as in drinking water is required. In this regard, the mammalian organism is used to handle varying quantities of externally administered zinc, such that Zn2+ homeostasis is regulated via control mechanisms of absorption and excretion. In humans, the average daily intake is estimated at about 15 mg of Zn2+. The available evidence from human studies points to a NOEL of about 0.5 mg/kg/day and thus confirms the safe exposure level, which could be predicted from the animal data. A series of human experimental studies have been published which report adverse effects from oral administration of zinc salts : * 47 healthy volunteers ingested ZnSO4 tablets three times a day for 6 weeks, resulting in a total daily dose of 2 mg Zn2+/kg bw. Headaches, nausea, vomiting, loss of appetite and abdominal cramps were seen in 26 of the volunteers. Ref. : 15 * Oral doses of 160 mg ZnSO4/day (2","page":7,"pdf":"out222_en.pdf","row_type":"noael_study","study_id":"out222_en_noael_003"}
SCCNFP_vision_codex NOAEL =42.5 mg/kg rabbit oral developmental developmental toxicity {"citation":"Ref. : 27 Species : Female Dutch rabbits Number of animals : 14-19 animals per group Test substance : ZnSO4 (unspecified) 6-amino-nicotinamide (positive control) Doses : ZnSO4 : 0, 0","dose":"Results No compound-related effects were observed at any dose level.","effect":"a lutea, implantations, viable foetuses and resorptions. All foetuses were weighed, sexed and examined for gross external defects. In addition, skeletal examinations (in two-thirds of the foetuses) and soft tissue examinations (in the remaining one-third of foetuses) were performed. Results No compound-related effects were observed at any dose level. In particular, there was no indication of any specific teratogenic activity of ZnSO4 under the conditions of this experiment. Conclusion The No Observed Effect Level (NOEL) with regard to maternal and developmental toxicity of ZnSO4 was 42.5 mg/kg (corresponding to about 17 mg/kg if expressed as zinc). Ref. : 27 Species : Female Dutch rabbits Number of animals : 14-19 animals per group Test substance : ZnSO4 (unspecified) 6-amino-nicotinamide (positive control) Doses : ZnSO4 : 0, 0.6, 2.8, 13.0 and 60.0 mg/kg by gavage in water 6-amino-nicotinamide : 2.5 mg/kg by gavage Exposure period : ZnSO4: day 6-18 of gestation (p.c.) 6-amino-nicotinamide: single application at day 19 of gestat","page":13,"pdf":"out222_en.pdf","row_type":"noael_study","study_id":"out222_en_noael_004"}
SCCNFP_vision_codex NOAEL =60 mg/kg rat oral developmental developmental toxicity {"citation":"Ref. : 28 Species : Female Sprague Dawley: CFE rats Number of animals : 10 animals per group Test substance : ZnO Doses and exposure period 7 groups received the test substance at levels","dose":"Zinc oxide ____________________________________________________________________________________________ 14 Conclusion The No Observed Effect Level (NOEL) with regard to maternal and developmental toxicity of Zinc Sulfate was at least 60.0 mg/kg (corresponding to about 24 mg/kg if expressed as zinc).","effect":"SCCNFP/0649/03, final Evaluation and opinion on : Zinc oxide ____________________________________________________________________________________________ 14 Conclusion The No Observed Effect Level (NOEL) with regard to maternal and developmental toxicity of Zinc Sulfate was at least 60.0 mg/kg (corresponding to about 24 mg/kg if expressed as zinc). Ref. : 28 Species : Female Sprague Dawley: CFE rats Number of animals : 10 animals per group Test substance : ZnO Doses and exposure period 7 groups received the test substance at levels of 2000 (about 100 mg/kg/d) or 4000 ppm (about 200 mg/kg/day) in the diet. 7 equally sized control groups received the basal diet without test substance. 4 groups were fed the test die","page":14,"pdf":"out222_en.pdf","row_type":"noael_study","study_id":"out222_en_noael_005"}
SCCNFP_vision_codex NOAEL =40 % human oral developmental developmental toxicity {"citation":"Ref. : 29 2","dose":"Conclusion ZnO, 2000 ppm, administered from day 21 prior to mating until day 15 of gestation induced no adverse effects on foetal development.","effect":"e observed in foetal whole body samples. These analytical results support the interpretation that the observed developmental effects of exaggerated high zinc doses are mediated by depletion of certain essential minerals such as copper. Conclusion ZnO, 2000 ppm, administered from day 21 prior to mating until day 15 of gestation induced no adverse effects on foetal development. This dietary level corresponds to a daily dose of about 100 mg/kg expressed as ZnO, or about 80 mg/kg expressed as zinc which represents the NOEL in this study. Ref. : 29 2.7. Toxicokinetics (incl. Percutaneous Absorption) Method : In vivo, human Volunteers: : 6 healthy males Test substance : ZnO Site of application : Chest, upper and lower legs Exposure : Daily application of 40% ZnO in ointment for a of period 10 days","page":14,"pdf":"out222_en.pdf","row_type":"noael_study","study_id":"out222_en_noael_006"}
SCCNFP_vision_codex NOAEL =3000 ppm rat - - NOAEL study {"dose":"e and cholesterol were reduced and alkaline phosphatase and urea nitrogen were increased in high dose animals.","effect":"e and cholesterol were reduced and alkaline phosphatase and urea nitrogen were increased in high dose animals. High dose females showed reduced ALAT and increased calcium levels, ASAT was increased in high dose males. Absolute and relative thyroid weights of males and kidney weights of females were increased at the highest dose. Gross pathology and histopathology showed changes in kidneys, thyroids, pancreas (degeneration/necrosis of acinar cells, clarification of nucleoli), gastrointestinal tract, and spleen. The NOEL for mice in this study was found at the mid dose at 3000 ppm (about 470 mg ZnSO4.7 H2O/kg bw (104 mg Zn2+/kg bw). Wistar rats : at the high dose level a moderate reduction in leucocyte counts, slightly decreased hematocrit and haemoglobin values (males only) and decreased total protein and cholesterol values were recorded. Absolute and relative liver weights and relative kidney weights were decreased in high dose males. Histopathology showed pancreatic damage (degeneration, necrosis of acinar cells, clarification","page":7,"pdf":"out222_en.pdf","row_type":"noael_study","study_id":"out222_en_noael_001"}
SCCNFP_vision_codex NOAEL =0.5 mg/kg/day human oral 6 weeks NOAEL study {"citation":"Ref. : 14 Human studies Since zinc is an essential trace element for all mammalian species, its presence in the diet of humans and animals as well as in drinking water is required","dose":"In this regard, the mammalian organism is used to handle varying quantities of externally administered zinc, such that Zn2+ homeostasis is regulated via control mechanisms of absorption and excretion.","effect":"2+/kg bw). Ref. : 14 Human studies Since zinc is an essential trace element for all mammalian species, its presence in the diet of humans and animals as well as in drinking water is required. In this regard, the mammalian organism is used to handle varying quantities of externally administered zinc, such that Zn2+ homeostasis is regulated via control mechanisms of absorption and excretion. In humans, the average daily intake is estimated at about 15 mg of Zn2+. The available evidence from human studies points to a NOEL of about 0.5 mg/kg/day and thus confirms the safe exposure level, which could be predicted from the animal data. A series of human experimental studies have been published which report adverse effects from oral administration of zinc salts : * 47 healthy volunteers ingested ZnSO4 tablets three times a day for 6 weeks, resulting in a total daily dose of 2 mg Zn2+/kg bw. Headaches, nausea, vomiting, loss of appetite and abdominal cramps were seen in 26 of the volunteers. Ref. : 15 * Oral doses of 160 mg ZnSO4/day (2","page":7,"pdf":"out222_en.pdf","row_type":"noael_study","study_id":"out222_en_noael_003"}
SCCNFP_vision_codex NOAEL =42.5 mg/kg rabbit oral developmental developmental toxicity {"citation":"Ref. : 27 Species : Female Dutch rabbits Number of animals : 14-19 animals per group Test substance : ZnSO4 (unspecified) 6-amino-nicotinamide (positive control) Doses : ZnSO4 : 0, 0","dose":"Results No compound-related effects were observed at any dose level.","effect":"a lutea, implantations, viable foetuses and resorptions. All foetuses were weighed, sexed and examined for gross external defects. In addition, skeletal examinations (in two-thirds of the foetuses) and soft tissue examinations (in the remaining one-third of foetuses) were performed. Results No compound-related effects were observed at any dose level. In particular, there was no indication of any specific teratogenic activity of ZnSO4 under the conditions of this experiment. Conclusion The No Observed Effect Level (NOEL) with regard to maternal and developmental toxicity of ZnSO4 was 42.5 mg/kg (corresponding to about 17 mg/kg if expressed as zinc). Ref. : 27 Species : Female Dutch rabbits Number of animals : 14-19 animals per group Test substance : ZnSO4 (unspecified) 6-amino-nicotinamide (positive control) Doses : ZnSO4 : 0, 0.6, 2.8, 13.0 and 60.0 mg/kg by gavage in water 6-amino-nicotinamide : 2.5 mg/kg by gavage Exposure period : ZnSO4: day 6-18 of gestation (p.c.) 6-amino-nicotinamide: single application at day 19 of gestat","page":13,"pdf":"out222_en.pdf","row_type":"noael_study","study_id":"out222_en_noael_004"}
SCCNFP_vision_codex NOAEL =60 mg/kg rat oral developmental developmental toxicity {"citation":"Ref. : 28 Species : Female Sprague Dawley: CFE rats Number of animals : 10 animals per group Test substance : ZnO Doses and exposure period 7 groups received the test substance at levels","dose":"Zinc oxide ____________________________________________________________________________________________ 14 Conclusion The No Observed Effect Level (NOEL) with regard to maternal and developmental toxicity of Zinc Sulfate was at least 60.0 mg/kg (corresponding to about 24 mg/kg if expressed as zinc).","effect":"SCCNFP/0649/03, final Evaluation and opinion on : Zinc oxide ____________________________________________________________________________________________ 14 Conclusion The No Observed Effect Level (NOEL) with regard to maternal and developmental toxicity of Zinc Sulfate was at least 60.0 mg/kg (corresponding to about 24 mg/kg if expressed as zinc). Ref. : 28 Species : Female Sprague Dawley: CFE rats Number of animals : 10 animals per group Test substance : ZnO Doses and exposure period 7 groups received the test substance at levels of 2000 (about 100 mg/kg/d) or 4000 ppm (about 200 mg/kg/day) in the diet. 7 equally sized control groups received the basal diet without test substance. 4 groups were fed the test die","page":14,"pdf":"out222_en.pdf","row_type":"noael_study","study_id":"out222_en_noael_005"}
SCCNFP_vision_codex NOAEL =40 % human oral developmental developmental toxicity {"citation":"Ref. : 29 2","dose":"Conclusion ZnO, 2000 ppm, administered from day 21 prior to mating until day 15 of gestation induced no adverse effects on foetal development.","effect":"e observed in foetal whole body samples. These analytical results support the interpretation that the observed developmental effects of exaggerated high zinc doses are mediated by depletion of certain essential minerals such as copper. Conclusion ZnO, 2000 ppm, administered from day 21 prior to mating until day 15 of gestation induced no adverse effects on foetal development. This dietary level corresponds to a daily dose of about 100 mg/kg expressed as ZnO, or about 80 mg/kg expressed as zinc which represents the NOEL in this study. Ref. : 29 2.7. Toxicokinetics (incl. Percutaneous Absorption) Method : In vivo, human Volunteers: : 6 healthy males Test substance : ZnO Site of application : Chest, upper and lower legs Exposure : Daily application of 40% ZnO in ointment for a of period 10 days","page":14,"pdf":"out222_en.pdf","row_type":"noael_study","study_id":"out222_en_noael_006"}
SCCNFP_vision_codex NOAEL =3000 ppm rat - - NOAEL study {"dose":"e and cholesterol were reduced and alkaline phosphatase and urea nitrogen were increased in high dose animals.","effect":"e and cholesterol were reduced and alkaline phosphatase and urea nitrogen were increased in high dose animals. High dose females showed reduced ALAT and increased calcium levels, ASAT was increased in high dose males. Absolute and relative thyroid weights of males and kidney weights of females were increased at the highest dose. Gross pathology and histopathology showed changes in kidneys, thyroids, pancreas (degeneration/necrosis of acinar cells, clarification of nucleoli), gastrointestinal tract, and spleen. The NOEL for mice in this study was found at the mid dose at 3000 ppm (about 470 mg ZnSO4.7 H2O/kg bw (104 mg Zn2+/kg bw). Wistar rats : at the high dose level a moderate reduction in leucocyte counts, slightly decreased hematocrit and haemoglobin values (males only) and decreased total protein and cholesterol values were recorded. Absolute and relative liver weights and relative kidney weights were decreased in high dose males. Histopathology showed pancreatic damage (degeneration, necrosis of acinar cells, clarification","page":7,"pdf":"out222_en.pdf","row_type":"noael_study","study_id":"out222_en_noael_001"}
SCCNFP_vision_codex NOAEL =0.5 mg/kg/day human oral 6 weeks NOAEL study {"citation":"Ref. : 14 Human studies Since zinc is an essential trace element for all mammalian species, its presence in the diet of humans and animals as well as in drinking water is required","dose":"In this regard, the mammalian organism is used to handle varying quantities of externally administered zinc, such that Zn2+ homeostasis is regulated via control mechanisms of absorption and excretion.","effect":"2+/kg bw). Ref. : 14 Human studies Since zinc is an essential trace element for all mammalian species, its presence in the diet of humans and animals as well as in drinking water is required. In this regard, the mammalian organism is used to handle varying quantities of externally administered zinc, such that Zn2+ homeostasis is regulated via control mechanisms of absorption and excretion. In humans, the average daily intake is estimated at about 15 mg of Zn2+. The available evidence from human studies points to a NOEL of about 0.5 mg/kg/day and thus confirms the safe exposure level, which could be predicted from the animal data. A series of human experimental studies have been published which report adverse effects from oral administration of zinc salts : * 47 healthy volunteers ingested ZnSO4 tablets three times a day for 6 weeks, resulting in a total daily dose of 2 mg Zn2+/kg bw. Headaches, nausea, vomiting, loss of appetite and abdominal cramps were seen in 26 of the volunteers. Ref. : 15 * Oral doses of 160 mg ZnSO4/day (2","page":7,"pdf":"out222_en.pdf","row_type":"noael_study","study_id":"out222_en_noael_003"}
SCCNFP_vision_codex NOAEL =42.5 mg/kg rabbit oral developmental developmental toxicity {"citation":"Ref. : 27 Species : Female Dutch rabbits Number of animals : 14-19 animals per group Test substance : ZnSO4 (unspecified) 6-amino-nicotinamide (positive control) Doses : ZnSO4 : 0, 0","dose":"Results No compound-related effects were observed at any dose level.","effect":"a lutea, implantations, viable foetuses and resorptions. All foetuses were weighed, sexed and examined for gross external defects. In addition, skeletal examinations (in two-thirds of the foetuses) and soft tissue examinations (in the remaining one-third of foetuses) were performed. Results No compound-related effects were observed at any dose level. In particular, there was no indication of any specific teratogenic activity of ZnSO4 under the conditions of this experiment. Conclusion The No Observed Effect Level (NOEL) with regard to maternal and developmental toxicity of ZnSO4 was 42.5 mg/kg (corresponding to about 17 mg/kg if expressed as zinc). Ref. : 27 Species : Female Dutch rabbits Number of animals : 14-19 animals per group Test substance : ZnSO4 (unspecified) 6-amino-nicotinamide (positive control) Doses : ZnSO4 : 0, 0.6, 2.8, 13.0 and 60.0 mg/kg by gavage in water 6-amino-nicotinamide : 2.5 mg/kg by gavage Exposure period : ZnSO4: day 6-18 of gestation (p.c.) 6-amino-nicotinamide: single application at day 19 of gestat","page":13,"pdf":"out222_en.pdf","row_type":"noael_study","study_id":"out222_en_noael_004"}
SCCNFP_vision_codex NOAEL =60 mg/kg rat oral developmental developmental toxicity {"citation":"Ref. : 28 Species : Female Sprague Dawley: CFE rats Number of animals : 10 animals per group Test substance : ZnO Doses and exposure period 7 groups received the test substance at levels","dose":"Zinc oxide ____________________________________________________________________________________________ 14 Conclusion The No Observed Effect Level (NOEL) with regard to maternal and developmental toxicity of Zinc Sulfate was at least 60.0 mg/kg (corresponding to about 24 mg/kg if expressed as zinc).","effect":"SCCNFP/0649/03, final Evaluation and opinion on : Zinc oxide ____________________________________________________________________________________________ 14 Conclusion The No Observed Effect Level (NOEL) with regard to maternal and developmental toxicity of Zinc Sulfate was at least 60.0 mg/kg (corresponding to about 24 mg/kg if expressed as zinc). Ref. : 28 Species : Female Sprague Dawley: CFE rats Number of animals : 10 animals per group Test substance : ZnO Doses and exposure period 7 groups received the test substance at levels of 2000 (about 100 mg/kg/d) or 4000 ppm (about 200 mg/kg/day) in the diet. 7 equally sized control groups received the basal diet without test substance. 4 groups were fed the test die","page":14,"pdf":"out222_en.pdf","row_type":"noael_study","study_id":"out222_en_noael_005"}
SCCNFP_vision_codex NOAEL =40 % human oral developmental developmental toxicity {"citation":"Ref. : 29 2","dose":"Conclusion ZnO, 2000 ppm, administered from day 21 prior to mating until day 15 of gestation induced no adverse effects on foetal development.","effect":"e observed in foetal whole body samples. These analytical results support the interpretation that the observed developmental effects of exaggerated high zinc doses are mediated by depletion of certain essential minerals such as copper. Conclusion ZnO, 2000 ppm, administered from day 21 prior to mating until day 15 of gestation induced no adverse effects on foetal development. This dietary level corresponds to a daily dose of about 100 mg/kg expressed as ZnO, or about 80 mg/kg expressed as zinc which represents the NOEL in this study. Ref. : 29 2.7. Toxicokinetics (incl. Percutaneous Absorption) Method : In vivo, human Volunteers: : 6 healthy males Test substance : ZnO Site of application : Chest, upper and lower legs Exposure : Daily application of 40% ZnO in ointment for a of period 10 days","page":14,"pdf":"out222_en.pdf","row_type":"noael_study","study_id":"out222_en_noael_006"}
SCCS_vision_codex 60 endpoints
Source Endpoint Type Value Unit Species Route Duration Study Type Reference
SCCS_vision_codex NOAEL =1000 mg/kg mouse oral - NOAEL study {"citation":"Reference: AR16)","dose":"hip, many effects were noted at the highest dose administered that should be considered dose related even when they only occur at the highest dose.","effect":"hip, many effects were noted at the highest dose administered that should be considered dose related even when they only occur at the highest dose. The pathological findings indicate a dose response relationship with the highest dose inducing the most severe alterations. The lowest dose investigated (1,000 mg/kg) also induced pathological effects in the animals. Most effects showed some minor differences between the 20 and 120 nm sized ZnO. Target organs for toxicity were liver, heart, spleen, pancreas and bone. A no observed adverse effect level (NOAEL) was not dentified because alterations were also observed at the lowest dose investigated (1,000 mg/kg). No deaths were observed in a similar study using a single oral dose of 5 mg/kg in mice (Reference: AR16). ZnO nanoparticles were approximately 50 nm in size (TEM evaluation), which were compared to ZnO microparticles showing at least one diameter >100 nm (TEM evaluation). DLS evaluation showed an average hydrodynamic diameter of 1,226 ± 120 nm for the ZnO microparticles, and an average hydrodynamic diame","page":29,"pdf":"sccs_o_103.pdf","row_type":"noael_study","study_id":"sccs_o_103_noael_001"}
SCCS_vision_codex NOAEL =1 mg/kg bw rat intravenous - repeated dose toxicity {"citation":"(References: 85, 94, 119)","dose":"In view of the indications for liver damage, a repeated dose toxicity study would have provided better information on potential toxicity.","effect":"toxic reactions were not observed. In view of the indications for liver damage, a repeated dose toxicity study would have provided better information on potential toxicity. In conclusion, after intravenous administration obtaining an internal dose of 5 mg/kg bw alterations in clinical pathology were observed that were indicative of liver damage. The liver damage appeared to be transient as similar alterations were not observed at four weeks after the single administration. Based on this study, the SCCS considers a NOAEL of 1 mg/kg bw for acute toxicity of ZnO in rats after intravenous administration. Additional studies submitted Additional information was included in the dossier on ZnO commercially obtained from Sigma-Aldrich and not related to the ZnO presented in the dossier. (References: 85, 94, 119)","page":86,"pdf":"sccs_o_103.pdf","row_type":"noael_study","study_id":"sccs_o_103_noael_003"}
SCCS_vision_codex NOAEL =2 % human oral 18 days repeated dose toxicity {"dose":"An NOAEL of 50 mg Zn2+/day was derived from a 10-week oral study with human volunteers and was used as a starting point for the risk characterization for repeated dose toxicity.","effect":"nc or zinc compounds is therefore chosen to be 2%. Based on the physical appearance, for dust exposure to zinc or zinc compounds a 10-fold lower default value of 0.2% is chosen in the risk assessment. For sunscreen containing 10% zinc oxide the following exposure assessment was performed: By an application of 9 g sunscreen/event, 3 events/day during 18 days/year the exposure will be 1,332 mg sunscreen/day, being 107 mg Zn2+/day. Assuming a dermal absorption of 2% the uptake is estimated to be 2.14 mg Zn2+/ day. An NOAEL of 50 mg Zn2+/day was derived from a 10-week oral study with human volunteers and was used as a starting point for the risk characterization for repeated dose toxicity. This NOAEL of 50 mg Zn2+/day results in an internal NOAEL of 10 mg Zn2+/day by correction for oral absorption (20%; worst case, because of the homeostasis the relative absorption will be smaller by excess of Zn2+-intake). Given that this study was with women (the most sensitive population in zinc supplementation studies), and that in women clinical","page":89,"pdf":"sccs_o_103.pdf","row_type":"noael_study","study_id":"sccs_o_103_noael_004"}
SCCS_vision_codex NOAEL =20 % human oral 18 days repeated dose toxicity {"dose":"An NOAEL of 50 mg Zn2+/day was derived from a 10-week oral study with human volunteers and was used as a starting point for the risk characterization for repeated dose toxicity.","effect":"the risk assessment. For sunscreen containing 10% zinc oxide the following exposure assessment was performed: By an application of 9 g sunscreen/event, 3 events/day during 18 days/year the exposure will be 1,332 mg sunscreen/day, being 107 mg Zn2+/day. Assuming a dermal absorption of 2% the uptake is estimated to be 2.14 mg Zn2+/ day. An NOAEL of 50 mg Zn2+/day was derived from a 10-week oral study with human volunteers and was used as a starting point for the risk characterization for repeated dose toxicity. This NOAEL of 50 mg Zn2+/day results in an internal NOAEL of 10 mg Zn2+/day by correction for oral absorption (20%; worst case, because of the homeostasis the relative absorption will be smaller by excess of Zn2+-intake). Given that this study was with women (the most sensitive population in zinc supplementation studies), and that in women clinical signs begin to appear only at a dose three times this NOAEL, a minimal MOS of 1 is considered sufficient when comparing the human NOAEL with the exposure levels for workers/consum","page":89,"pdf":"sccs_o_103.pdf","row_type":"noael_study","study_id":"sccs_o_103_noael_005"}
SCCS_vision_codex NOAEL =1 - human - - NOAEL study {"dose":"t this study was with women (the most sensitive population in zinc supplementation studies), and that in women clinical signs begin to appear only at a dose three times this NOAEL, a minimal MOS of 1 is considered sufficient when comparing the human NOAEL with the exposure levels for workers/consumers/general population.","effect":"t this study was with women (the most sensitive population in zinc supplementation studies), and that in women clinical signs begin to appear only at a dose three times this NOAEL, a minimal MOS of 1 is considered sufficient when comparing the human NOAEL with the exposure levels for workers/consumers/general population. The MOS between this internal NOAEL and the internal exposure as a result of exposure to sunscreen formulations is 5, which is a factor of 5 larger than the minimal MOS. The SCCS agrees with the NOAEL indicated in the RAR statement. Therefore, this information is used together with the data from the absorption study provided in the dossier and exposure assumptions from the SCCS Notes of Guidance for the risk assessment of zinc oxide nanoparticles in sun screens as follows:","page":89,"pdf":"sccs_o_103.pdf","row_type":"noael_study","study_id":"sccs_o_103_noael_010"}
SCCS_vision_codex NOAEL =0.0225 mg/kg bw/d human oral - NOAEL study {"citation":"Reference: 36) Amount absorbed/day (18,000 × 25%/100 × 0","dose":"36) Amount absorbed/day (18,000 × 25%/100 × 0.03%/100) 1.35 mg Typical body weight of human 60 kg Systemic exposure dose (1.35 mg/60 kg) 0.0225 mg/kg bw/d No Observed Adverse Effect Level NOAEL (oral, human, sensitive subpopulation)** 0.166 mg/kg bw/d Margin of Safety NOAEL/SED = 7.4 * Standard amount as indicated in the SCCS Notes of Guidance f...","effect":"inc oxide (nano form) ___________________________________________________________________________________________ 90 Calculation of the margin of safety for ZnO (nano) (See section 3.1.16 for the range of nano-ZnO covered by this opinion) Amount of sunscreen applied* 18,000 mg Maximum concentration of ZnO 25% Absorption through the skin 0.03% (Reference: 36) Amount absorbed/day (18,000 × 25%/100 × 0.03%/100) 1.35 mg Typical body weight of human 60 kg Systemic exposure dose (1.35 mg/60 kg) 0.0225 mg/kg bw/d No Observed Adverse Effect Level NOAEL (oral, human, sensitive subpopulation)** 0.166 mg/kg bw/d Margin of Safety NOAEL/SED = 7.4 * Standard amount as indicated in the SCCS Notes of Guidance for the testing of cosmetic ingredients and their safety evaluation SCCS/1416/11 ** The internal NOAEL for ZnO is 10 mg Zn2+/day = 10/60= 0.166 mg /kg bw per day (Reference 44, sub III) The calculation of the exposure via sun protection products to ZnO nanoparticles assuming Zn2+ uptake results in a MoS of 7.4. Given that the NOAEL is derived from a study on","page":90,"pdf":"sccs_o_103.pdf","row_type":"noael_study","study_id":"sccs_o_103_noael_011"}
SCCS_vision_codex NOAEL =0.166 mg/kg bw/d human oral - NOAEL study {"citation":"Reference: 36) Amount absorbed/day (18,000 × 25%/100 × 0","dose":"36) Amount absorbed/day (18,000 × 25%/100 × 0.03%/100) 1.35 mg Typical body weight of human 60 kg Systemic exposure dose (1.35 mg/60 kg) 0.0225 mg/kg bw/d No Observed Adverse Effect Level NOAEL (oral, human, sensitive subpopulation)** 0.166 mg/kg bw/d Margin of Safety NOAEL/SED = 7.4 * Standard amount as indicated in the SCCS Notes of Guidance f...","effect":"________________________________________________________________________________ 90 Calculation of the margin of safety for ZnO (nano) (See section 3.1.16 for the range of nano-ZnO covered by this opinion) Amount of sunscreen applied* 18,000 mg Maximum concentration of ZnO 25% Absorption through the skin 0.03% (Reference: 36) Amount absorbed/day (18,000 × 25%/100 × 0.03%/100) 1.35 mg Typical body weight of human 60 kg Systemic exposure dose (1.35 mg/60 kg) 0.0225 mg/kg bw/d No Observed Adverse Effect Level NOAEL (oral, human, sensitive subpopulation)** 0.166 mg/kg bw/d Margin of Safety NOAEL/SED = 7.4 * Standard amount as indicated in the SCCS Notes of Guidance for the testing of cosmetic ingredients and their safety evaluation SCCS/1416/11 ** The internal NOAEL for ZnO is 10 mg Zn2+/day = 10/60= 0.166 mg /kg bw per day (Reference 44, sub III) The calculation of the exposure via sun protection products to ZnO nanoparticles assuming Zn2+ uptake results in a MoS of 7.4. Given that the NOAEL is derived from a study on women","page":90,"pdf":"sccs_o_103.pdf","row_type":"noael_study","study_id":"sccs_o_103_noael_012"}
SCCS_vision_codex NOAEL =0.9 mg/kg/d human oral - NOAEL study {"citation":"(Reference 44, sub III)","dose":"CS/1416/11 ** The internal NOAEL for ZnO is 10 mg Zn2+/day = 10/60= 0.166 mg /kg bw per day (Reference 44, sub III) The calculation of the exposure via sun protection products to ZnO nanoparticles assuming Zn2+ uptake results in a MoS of 7.4.","effect":"CS/1416/11 ** The internal NOAEL for ZnO is 10 mg Zn2+/day = 10/60= 0.166 mg /kg bw per day (Reference 44, sub III) The calculation of the exposure via sun protection products to ZnO nanoparticles assuming Zn2+ uptake results in a MoS of 7.4. Given that the NOAEL is derived from a study on women (the most sensitive population in zinc supplementation studies), and that in women clinical signs begin to appear only at a dose three times this NOAEL, a minimal MOS of 1 is considered sufficient when comparing the human NOAEL with the exposure levels for workers/consumers/general population (Reference 44, sub III). Calculation of the Margin of Safety for Lip products According to the SCCS Notes of Guidance for the testing of cosmetic ingredients and their safety evaluation (SCCS/1416/11) the daily exposure to lipstick/lipproducts is 0.9 mg/kg/d. Exposure dose (0.9 x 25%) 0.225 mg/kg bw/day. No Observed Adverse Effect Level NOAEL (oral, human)* 0.83 mg/kg bw/d Margin of Safety NOAEL/ED** = 3.7 * The NOAEL for ZnO is 50 mg Zn2+/day =","page":90,"pdf":"sccs_o_103.pdf","row_type":"noael_study","study_id":"sccs_o_103_noael_017"}
SCCS_vision_codex NOAEL =0.225 mg/kg bw/day human oral - NOAEL study {"citation":"(Reference 44, sub III)","dose":"clinical signs begin to appear only at a dose three times this NOAEL, a minimal MOS of 1 is considered sufficient when comparing the human NOAEL with the exposure levels for workers/consumers/general population (Reference 44, sub III).","effect":"clinical signs begin to appear only at a dose three times this NOAEL, a minimal MOS of 1 is considered sufficient when comparing the human NOAEL with the exposure levels for workers/consumers/general population (Reference 44, sub III). Calculation of the Margin of Safety for Lip products According to the SCCS Notes of Guidance for the testing of cosmetic ingredients and their safety evaluation (SCCS/1416/11) the daily exposure to lipstick/lipproducts is 0.9 mg/kg/d. Exposure dose (0.9 x 25%) 0.225 mg/kg bw/day. No Observed Adverse Effect Level NOAEL (oral, human)* 0.83 mg/kg bw/d Margin of Safety NOAEL/ED** = 3.7 * The NOAEL for ZnO is 50 mg Zn2+/day = 50/60= 0.83 mg /kg bw per day (Reference 44, sub III) ** Since route to route extrapolation is not needed, the (external) NOAEL is compared to the (external) exposure dose It is expected that the exposure to lipstick/lip products that contain high SPF factors (eg ZnO nanomaterial) is less than the exposure to ‘regular’ lipstick/lip products. Typically, these products are used only in specific time fram","page":90,"pdf":"sccs_o_103.pdf","row_type":"noael_study","study_id":"sccs_o_103_noael_018"}
SCCS_vision_codex NOAEL =0.83 mg/kg bw/d human oral - NOAEL study {"citation":"(Reference 44, sub III)","dose":"nly at a dose three times this NOAEL, a minimal MOS of 1 is considered sufficient when comparing the human NOAEL with the exposure levels for workers/consumers/general population (Reference 44, sub III).","effect":"nly at a dose three times this NOAEL, a minimal MOS of 1 is considered sufficient when comparing the human NOAEL with the exposure levels for workers/consumers/general population (Reference 44, sub III). Calculation of the Margin of Safety for Lip products According to the SCCS Notes of Guidance for the testing of cosmetic ingredients and their safety evaluation (SCCS/1416/11) the daily exposure to lipstick/lipproducts is 0.9 mg/kg/d. Exposure dose (0.9 x 25%) 0.225 mg/kg bw/day. No Observed Adverse Effect Level NOAEL (oral, human)* 0.83 mg/kg bw/d Margin of Safety NOAEL/ED** = 3.7 * The NOAEL for ZnO is 50 mg Zn2+/day = 50/60= 0.83 mg /kg bw per day (Reference 44, sub III) ** Since route to route extrapolation is not needed, the (external) NOAEL is compared to the (external) exposure dose It is expected that the exposure to lipstick/lip products that contain high SPF factors (eg ZnO nanomaterial) is less than the exposure to ‘regular’ lipstick/lip products. Typically, these products are used only in specific time frames, e.","page":90,"pdf":"sccs_o_103.pdf","row_type":"noael_study","study_id":"sccs_o_103_noael_019"}
SCCS_vision_codex NOAEL =50 - mouse oral - NOAEL study {"citation":"(Reference 44, sub III)","dose":"However, no differences weren observed between ZnO administered as nanoscale or microscale particles.","effect":"ure In one exploratory study in mice, systemic availability of Zn was indicated after a single oral exposure. However, no differences weren observed between ZnO administered as nanoscale or microscale particles. It is likely that absorbed Zn in the GI-tract was in the dissolved ionic form. In view of the data provided, oral exposure of nano-ZnO via applications of nano-ZnO as a cosmetic ingredient in sunscreens should be considered to be of a similar risk to micron-sized ZnO as previously evaluated in the RAR. The NOAEL for oral intake of ZnO is 50 mg /bw day (Reference 44, sub III). The oral exposure to ZnO nanoparticles as cosmetic ingredient in sunscreens is limited to accidental ingestion of small fractions of lip products and sun protection products and can be considered to be low. Inhalation exposure Upon inhalation of ZnO nanoparticles, serious local effects in the lung were observed. Even if this may be due to the solubilized Zn ions, the effects are a direct result of the exposure to the ZnO nanoparticles. Therefore, th","page":96,"pdf":"sccs_o_103.pdf","row_type":"noael_study","study_id":"sccs_o_103_noael_023"}
SCCS_vision_codex NOAEL =90 - - inhalation 90 days NOAEL study {"dose":"Conclusions The study authors concluded that transient local effects on the respiratory tract were only observed in the highest dose group for this 90 days inhalation study.","effect":"upporting the rapid elimination. In the study four animals were found dead or killed moribund, the cause of death being in two animals a purulent and necrotizing inflammation of the urogenital organs, in one animal due to a pronounced malignant lymphoma, and in one animal due to unknown cause. These observations were not treatment related. Conclusions The study authors concluded that transient local effects on the respiratory tract were only observed in the highest dose group for this 90 days inhalation study. A NOAEL of 1.5 g/m³ can be identified for the test item Z-COTE® HP1. Under the conditions of this test no persistent toxicity was found and all lesions were found to be recovered within the 28 day post exposure period. SCCS comments The file received for the study report was not signed by the study director and/or scientists involved. The report was supposedly to be published by the end of 2012, however, it was not found on Cefic website (June 2013). Size distributions of both nano- and micron-sized ZnO particles used","page":12,"pdf":"sccs_o_137.pdf","row_type":"noael_study","study_id":"sccs_o_137_noael_001"}
SCCS_vision_codex NOAEL =1518 - - - - NOAEL study {"dose":"Statistical difference in total protein in BALF between high dose group Z-COTE® HP1 with controls not mentioned (high dose group 112.2 ± 8.7 vs control 79.6 ± 9.2 total protein).","effect":"SCCS/1518/13 Revision of the addendum to the opinion on zinc oxide (nano form) ___________________________________________________________________________________________ 13 animals were used. Some explanation might have given insight to how and why this was done. Statistical difference in total protein in BALF between high dose group Z-COTE® HP1 with controls not mentioned (high dose group 112.2 ± 8.7 vs control 79.6 ± 9.2 total protein). The NOAEL derived by the study authors is based on both observations in BAL and lung histopathology occurring at the high dose group and not in mid dose group of 1.5 mg/m3. However, the SCCS concludes on a NOAEL of 0.3 mg/ m3 in view of the ongoing activation of lung macrophages and lung draining lymph nodes. 4. CONCLUSION The SCCS concludes that ZnO nanomaterials with the following characteristics can be considered similar to the ZnO nanomaterials as evaluated in opinion SCCS/1489/12 and thus pose no or limited risk for","page":13,"pdf":"sccs_o_137.pdf","row_type":"noael_study","study_id":"sccs_o_137_noael_002"}
SCCS_vision_codex NOAEL =96 % - - - NOAEL study {"dose":"Statistical difference in total protein in BALF between high dose group Z-COTE® HP1 with controls not mentioned (high dose group 112.2 ± 8.7 vs control 79.6 ± 9.2 total protein).","effect":"______________________________________ 13 animals were used. Some explanation might have given insight to how and why this was done. Statistical difference in total protein in BALF between high dose group Z-COTE® HP1 with controls not mentioned (high dose group 112.2 ± 8.7 vs control 79.6 ± 9.2 total protein). The NOAEL derived by the study authors is based on both observations in BAL and lung histopathology occurring at the high dose group and not in mid dose group of 1.5 mg/m3. However, the SCCS concludes on a NOAEL of 0.3 mg/ m3 in view of the ongoing activation of lung macrophages and lung draining lymph nodes. 4. CONCLUSION The SCCS concludes that ZnO nanomaterials with the following characteristics can be considered similar to the ZnO nanomaterials as evaluated in opinion SCCS/1489/12 and thus pose no or limited risk for use on the skin as UV filter in sunscreen formulations: 1. ZnO nanoparticles of purity ≥96%, with wurtzite crystalline structure and physical appearance as clusters that are rod-like, star-like and/or","page":13,"pdf":"sccs_o_137.pdf","row_type":"noael_study","study_id":"sccs_o_137_noael_003"}
SCCS_vision_codex NOAEL =4 - - inhalation 90 days NOAEL study {"effect":". Other cosmetic ingredients can be used as coatings as long as they are demonstrated to the SCCS to be safe and do not affect the particle properties related to behaviour and/or effects, compared to the nanomaterials covered in the current opinion. 4. ZnO nanoparticles that have a comparable solubility to that reported in the dossier, i.e. below 50 mg/L (approximately the maximum solubility of the ZnO nanomaterials for which data are provided in the dossier). The submitted 90 days inhalation study resulted in a NOAEL of 0.3 mg/m3. However these new data do not address the concerns relating to the lung exposure and the potential manifestation of harmful effects. 5. MINORITY OPINION / 6. REFERENCES /","page":13,"pdf":"sccs_o_137.pdf","row_type":"noael_study","study_id":"sccs_o_137_noael_004"}
SCCS_vision_codex NOAEL =1000 mg/kg mouse oral - NOAEL study {"citation":"Reference: AR16)","dose":"hip, many effects were noted at the highest dose administered that should be considered dose related even when they only occur at the highest dose.","effect":"hip, many effects were noted at the highest dose administered that should be considered dose related even when they only occur at the highest dose. The pathological findings indicate a dose response relationship with the highest dose inducing the most severe alterations. The lowest dose investigated (1,000 mg/kg) also induced pathological effects in the animals. Most effects showed some minor differences between the 20 and 120 nm sized ZnO. Target organs for toxicity were liver, heart, spleen, pancreas and bone. A no observed adverse effect level (NOAEL) was not dentified because alterations were also observed at the lowest dose investigated (1,000 mg/kg). No deaths were observed in a similar study using a single oral dose of 5 mg/kg in mice (Reference: AR16). ZnO nanoparticles were approximately 50 nm in size (TEM evaluation), which were compared to ZnO microparticles showing at least one diameter >100 nm (TEM evaluation). DLS evaluation showed an average hydrodynamic diameter of 1,226 ± 120 nm for the ZnO microparticles, and an average hydrodynamic diame","page":29,"pdf":"sccs_o_103.pdf","row_type":"noael_study","study_id":"sccs_o_103_noael_001"}
SCCS_vision_codex NOAEL =1 mg/kg bw rat intravenous - repeated dose toxicity {"citation":"(References: 85, 94, 119)","dose":"In view of the indications for liver damage, a repeated dose toxicity study would have provided better information on potential toxicity.","effect":"toxic reactions were not observed. In view of the indications for liver damage, a repeated dose toxicity study would have provided better information on potential toxicity. In conclusion, after intravenous administration obtaining an internal dose of 5 mg/kg bw alterations in clinical pathology were observed that were indicative of liver damage. The liver damage appeared to be transient as similar alterations were not observed at four weeks after the single administration. Based on this study, the SCCS considers a NOAEL of 1 mg/kg bw for acute toxicity of ZnO in rats after intravenous administration. Additional studies submitted Additional information was included in the dossier on ZnO commercially obtained from Sigma-Aldrich and not related to the ZnO presented in the dossier. (References: 85, 94, 119)","page":86,"pdf":"sccs_o_103.pdf","row_type":"noael_study","study_id":"sccs_o_103_noael_003"}
SCCS_vision_codex NOAEL =2 % human oral 18 days repeated dose toxicity {"dose":"An NOAEL of 50 mg Zn2+/day was derived from a 10-week oral study with human volunteers and was used as a starting point for the risk characterization for repeated dose toxicity.","effect":"nc or zinc compounds is therefore chosen to be 2%. Based on the physical appearance, for dust exposure to zinc or zinc compounds a 10-fold lower default value of 0.2% is chosen in the risk assessment. For sunscreen containing 10% zinc oxide the following exposure assessment was performed: By an application of 9 g sunscreen/event, 3 events/day during 18 days/year the exposure will be 1,332 mg sunscreen/day, being 107 mg Zn2+/day. Assuming a dermal absorption of 2% the uptake is estimated to be 2.14 mg Zn2+/ day. An NOAEL of 50 mg Zn2+/day was derived from a 10-week oral study with human volunteers and was used as a starting point for the risk characterization for repeated dose toxicity. This NOAEL of 50 mg Zn2+/day results in an internal NOAEL of 10 mg Zn2+/day by correction for oral absorption (20%; worst case, because of the homeostasis the relative absorption will be smaller by excess of Zn2+-intake). Given that this study was with women (the most sensitive population in zinc supplementation studies), and that in women clinical","page":89,"pdf":"sccs_o_103.pdf","row_type":"noael_study","study_id":"sccs_o_103_noael_004"}
SCCS_vision_codex NOAEL =20 % human oral 18 days repeated dose toxicity {"dose":"An NOAEL of 50 mg Zn2+/day was derived from a 10-week oral study with human volunteers and was used as a starting point for the risk characterization for repeated dose toxicity.","effect":"the risk assessment. For sunscreen containing 10% zinc oxide the following exposure assessment was performed: By an application of 9 g sunscreen/event, 3 events/day during 18 days/year the exposure will be 1,332 mg sunscreen/day, being 107 mg Zn2+/day. Assuming a dermal absorption of 2% the uptake is estimated to be 2.14 mg Zn2+/ day. An NOAEL of 50 mg Zn2+/day was derived from a 10-week oral study with human volunteers and was used as a starting point for the risk characterization for repeated dose toxicity. This NOAEL of 50 mg Zn2+/day results in an internal NOAEL of 10 mg Zn2+/day by correction for oral absorption (20%; worst case, because of the homeostasis the relative absorption will be smaller by excess of Zn2+-intake). Given that this study was with women (the most sensitive population in zinc supplementation studies), and that in women clinical signs begin to appear only at a dose three times this NOAEL, a minimal MOS of 1 is considered sufficient when comparing the human NOAEL with the exposure levels for workers/consum","page":89,"pdf":"sccs_o_103.pdf","row_type":"noael_study","study_id":"sccs_o_103_noael_005"}
SCCS_vision_codex NOAEL =1 - human - - NOAEL study {"dose":"t this study was with women (the most sensitive population in zinc supplementation studies), and that in women clinical signs begin to appear only at a dose three times this NOAEL, a minimal MOS of 1 is considered sufficient when comparing the human NOAEL with the exposure levels for workers/consumers/general population.","effect":"t this study was with women (the most sensitive population in zinc supplementation studies), and that in women clinical signs begin to appear only at a dose three times this NOAEL, a minimal MOS of 1 is considered sufficient when comparing the human NOAEL with the exposure levels for workers/consumers/general population. The MOS between this internal NOAEL and the internal exposure as a result of exposure to sunscreen formulations is 5, which is a factor of 5 larger than the minimal MOS. The SCCS agrees with the NOAEL indicated in the RAR statement. Therefore, this information is used together with the data from the absorption study provided in the dossier and exposure assumptions from the SCCS Notes of Guidance for the risk assessment of zinc oxide nanoparticles in sun screens as follows:","page":89,"pdf":"sccs_o_103.pdf","row_type":"noael_study","study_id":"sccs_o_103_noael_010"}
SCCS_vision_codex NOAEL =0.0225 mg/kg bw/d human oral - NOAEL study {"citation":"Reference: 36) Amount absorbed/day (18,000 × 25%/100 × 0","dose":"36) Amount absorbed/day (18,000 × 25%/100 × 0.03%/100) 1.35 mg Typical body weight of human 60 kg Systemic exposure dose (1.35 mg/60 kg) 0.0225 mg/kg bw/d No Observed Adverse Effect Level NOAEL (oral, human, sensitive subpopulation)** 0.166 mg/kg bw/d Margin of Safety NOAEL/SED = 7.4 * Standard amount as indicated in the SCCS Notes of Guidance f...","effect":"inc oxide (nano form) ___________________________________________________________________________________________ 90 Calculation of the margin of safety for ZnO (nano) (See section 3.1.16 for the range of nano-ZnO covered by this opinion) Amount of sunscreen applied* 18,000 mg Maximum concentration of ZnO 25% Absorption through the skin 0.03% (Reference: 36) Amount absorbed/day (18,000 × 25%/100 × 0.03%/100) 1.35 mg Typical body weight of human 60 kg Systemic exposure dose (1.35 mg/60 kg) 0.0225 mg/kg bw/d No Observed Adverse Effect Level NOAEL (oral, human, sensitive subpopulation)** 0.166 mg/kg bw/d Margin of Safety NOAEL/SED = 7.4 * Standard amount as indicated in the SCCS Notes of Guidance for the testing of cosmetic ingredients and their safety evaluation SCCS/1416/11 ** The internal NOAEL for ZnO is 10 mg Zn2+/day = 10/60= 0.166 mg /kg bw per day (Reference 44, sub III) The calculation of the exposure via sun protection products to ZnO nanoparticles assuming Zn2+ uptake results in a MoS of 7.4. Given that the NOAEL is derived from a study on","page":90,"pdf":"sccs_o_103.pdf","row_type":"noael_study","study_id":"sccs_o_103_noael_011"}
SCCS_vision_codex NOAEL =0.166 mg/kg bw/d human oral - NOAEL study {"citation":"Reference: 36) Amount absorbed/day (18,000 × 25%/100 × 0","dose":"36) Amount absorbed/day (18,000 × 25%/100 × 0.03%/100) 1.35 mg Typical body weight of human 60 kg Systemic exposure dose (1.35 mg/60 kg) 0.0225 mg/kg bw/d No Observed Adverse Effect Level NOAEL (oral, human, sensitive subpopulation)** 0.166 mg/kg bw/d Margin of Safety NOAEL/SED = 7.4 * Standard amount as indicated in the SCCS Notes of Guidance f...","effect":"________________________________________________________________________________ 90 Calculation of the margin of safety for ZnO (nano) (See section 3.1.16 for the range of nano-ZnO covered by this opinion) Amount of sunscreen applied* 18,000 mg Maximum concentration of ZnO 25% Absorption through the skin 0.03% (Reference: 36) Amount absorbed/day (18,000 × 25%/100 × 0.03%/100) 1.35 mg Typical body weight of human 60 kg Systemic exposure dose (1.35 mg/60 kg) 0.0225 mg/kg bw/d No Observed Adverse Effect Level NOAEL (oral, human, sensitive subpopulation)** 0.166 mg/kg bw/d Margin of Safety NOAEL/SED = 7.4 * Standard amount as indicated in the SCCS Notes of Guidance for the testing of cosmetic ingredients and their safety evaluation SCCS/1416/11 ** The internal NOAEL for ZnO is 10 mg Zn2+/day = 10/60= 0.166 mg /kg bw per day (Reference 44, sub III) The calculation of the exposure via sun protection products to ZnO nanoparticles assuming Zn2+ uptake results in a MoS of 7.4. Given that the NOAEL is derived from a study on women","page":90,"pdf":"sccs_o_103.pdf","row_type":"noael_study","study_id":"sccs_o_103_noael_012"}
SCCS_vision_codex NOAEL =0.9 mg/kg/d human oral - NOAEL study {"citation":"(Reference 44, sub III)","dose":"CS/1416/11 ** The internal NOAEL for ZnO is 10 mg Zn2+/day = 10/60= 0.166 mg /kg bw per day (Reference 44, sub III) The calculation of the exposure via sun protection products to ZnO nanoparticles assuming Zn2+ uptake results in a MoS of 7.4.","effect":"CS/1416/11 ** The internal NOAEL for ZnO is 10 mg Zn2+/day = 10/60= 0.166 mg /kg bw per day (Reference 44, sub III) The calculation of the exposure via sun protection products to ZnO nanoparticles assuming Zn2+ uptake results in a MoS of 7.4. Given that the NOAEL is derived from a study on women (the most sensitive population in zinc supplementation studies), and that in women clinical signs begin to appear only at a dose three times this NOAEL, a minimal MOS of 1 is considered sufficient when comparing the human NOAEL with the exposure levels for workers/consumers/general population (Reference 44, sub III). Calculation of the Margin of Safety for Lip products According to the SCCS Notes of Guidance for the testing of cosmetic ingredients and their safety evaluation (SCCS/1416/11) the daily exposure to lipstick/lipproducts is 0.9 mg/kg/d. Exposure dose (0.9 x 25%) 0.225 mg/kg bw/day. No Observed Adverse Effect Level NOAEL (oral, human)* 0.83 mg/kg bw/d Margin of Safety NOAEL/ED** = 3.7 * The NOAEL for ZnO is 50 mg Zn2+/day =","page":90,"pdf":"sccs_o_103.pdf","row_type":"noael_study","study_id":"sccs_o_103_noael_017"}
SCCS_vision_codex NOAEL =0.225 mg/kg bw/day human oral - NOAEL study {"citation":"(Reference 44, sub III)","dose":"clinical signs begin to appear only at a dose three times this NOAEL, a minimal MOS of 1 is considered sufficient when comparing the human NOAEL with the exposure levels for workers/consumers/general population (Reference 44, sub III).","effect":"clinical signs begin to appear only at a dose three times this NOAEL, a minimal MOS of 1 is considered sufficient when comparing the human NOAEL with the exposure levels for workers/consumers/general population (Reference 44, sub III). Calculation of the Margin of Safety for Lip products According to the SCCS Notes of Guidance for the testing of cosmetic ingredients and their safety evaluation (SCCS/1416/11) the daily exposure to lipstick/lipproducts is 0.9 mg/kg/d. Exposure dose (0.9 x 25%) 0.225 mg/kg bw/day. No Observed Adverse Effect Level NOAEL (oral, human)* 0.83 mg/kg bw/d Margin of Safety NOAEL/ED** = 3.7 * The NOAEL for ZnO is 50 mg Zn2+/day = 50/60= 0.83 mg /kg bw per day (Reference 44, sub III) ** Since route to route extrapolation is not needed, the (external) NOAEL is compared to the (external) exposure dose It is expected that the exposure to lipstick/lip products that contain high SPF factors (eg ZnO nanomaterial) is less than the exposure to ‘regular’ lipstick/lip products. Typically, these products are used only in specific time fram","page":90,"pdf":"sccs_o_103.pdf","row_type":"noael_study","study_id":"sccs_o_103_noael_018"}
SCCS_vision_codex NOAEL =0.83 mg/kg bw/d human oral - NOAEL study {"citation":"(Reference 44, sub III)","dose":"nly at a dose three times this NOAEL, a minimal MOS of 1 is considered sufficient when comparing the human NOAEL with the exposure levels for workers/consumers/general population (Reference 44, sub III).","effect":"nly at a dose three times this NOAEL, a minimal MOS of 1 is considered sufficient when comparing the human NOAEL with the exposure levels for workers/consumers/general population (Reference 44, sub III). Calculation of the Margin of Safety for Lip products According to the SCCS Notes of Guidance for the testing of cosmetic ingredients and their safety evaluation (SCCS/1416/11) the daily exposure to lipstick/lipproducts is 0.9 mg/kg/d. Exposure dose (0.9 x 25%) 0.225 mg/kg bw/day. No Observed Adverse Effect Level NOAEL (oral, human)* 0.83 mg/kg bw/d Margin of Safety NOAEL/ED** = 3.7 * The NOAEL for ZnO is 50 mg Zn2+/day = 50/60= 0.83 mg /kg bw per day (Reference 44, sub III) ** Since route to route extrapolation is not needed, the (external) NOAEL is compared to the (external) exposure dose It is expected that the exposure to lipstick/lip products that contain high SPF factors (eg ZnO nanomaterial) is less than the exposure to ‘regular’ lipstick/lip products. Typically, these products are used only in specific time frames, e.","page":90,"pdf":"sccs_o_103.pdf","row_type":"noael_study","study_id":"sccs_o_103_noael_019"}
SCCS_vision_codex NOAEL =50 - mouse oral - NOAEL study {"citation":"(Reference 44, sub III)","dose":"However, no differences weren observed between ZnO administered as nanoscale or microscale particles.","effect":"ure In one exploratory study in mice, systemic availability of Zn was indicated after a single oral exposure. However, no differences weren observed between ZnO administered as nanoscale or microscale particles. It is likely that absorbed Zn in the GI-tract was in the dissolved ionic form. In view of the data provided, oral exposure of nano-ZnO via applications of nano-ZnO as a cosmetic ingredient in sunscreens should be considered to be of a similar risk to micron-sized ZnO as previously evaluated in the RAR. The NOAEL for oral intake of ZnO is 50 mg /bw day (Reference 44, sub III). The oral exposure to ZnO nanoparticles as cosmetic ingredient in sunscreens is limited to accidental ingestion of small fractions of lip products and sun protection products and can be considered to be low. Inhalation exposure Upon inhalation of ZnO nanoparticles, serious local effects in the lung were observed. Even if this may be due to the solubilized Zn ions, the effects are a direct result of the exposure to the ZnO nanoparticles. Therefore, th","page":96,"pdf":"sccs_o_103.pdf","row_type":"noael_study","study_id":"sccs_o_103_noael_023"}
SCCS_vision_codex NOAEL =90 - - inhalation 90 days NOAEL study {"dose":"Conclusions The study authors concluded that transient local effects on the respiratory tract were only observed in the highest dose group for this 90 days inhalation study.","effect":"upporting the rapid elimination. In the study four animals were found dead or killed moribund, the cause of death being in two animals a purulent and necrotizing inflammation of the urogenital organs, in one animal due to a pronounced malignant lymphoma, and in one animal due to unknown cause. These observations were not treatment related. Conclusions The study authors concluded that transient local effects on the respiratory tract were only observed in the highest dose group for this 90 days inhalation study. A NOAEL of 1.5 g/m³ can be identified for the test item Z-COTE® HP1. Under the conditions of this test no persistent toxicity was found and all lesions were found to be recovered within the 28 day post exposure period. SCCS comments The file received for the study report was not signed by the study director and/or scientists involved. The report was supposedly to be published by the end of 2012, however, it was not found on Cefic website (June 2013). Size distributions of both nano- and micron-sized ZnO particles used","page":12,"pdf":"sccs_o_137.pdf","row_type":"noael_study","study_id":"sccs_o_137_noael_001"}
SCCS_vision_codex NOAEL =1518 - - - - NOAEL study {"dose":"Statistical difference in total protein in BALF between high dose group Z-COTE® HP1 with controls not mentioned (high dose group 112.2 ± 8.7 vs control 79.6 ± 9.2 total protein).","effect":"SCCS/1518/13 Revision of the addendum to the opinion on zinc oxide (nano form) ___________________________________________________________________________________________ 13 animals were used. Some explanation might have given insight to how and why this was done. Statistical difference in total protein in BALF between high dose group Z-COTE® HP1 with controls not mentioned (high dose group 112.2 ± 8.7 vs control 79.6 ± 9.2 total protein). The NOAEL derived by the study authors is based on both observations in BAL and lung histopathology occurring at the high dose group and not in mid dose group of 1.5 mg/m3. However, the SCCS concludes on a NOAEL of 0.3 mg/ m3 in view of the ongoing activation of lung macrophages and lung draining lymph nodes. 4. CONCLUSION The SCCS concludes that ZnO nanomaterials with the following characteristics can be considered similar to the ZnO nanomaterials as evaluated in opinion SCCS/1489/12 and thus pose no or limited risk for","page":13,"pdf":"sccs_o_137.pdf","row_type":"noael_study","study_id":"sccs_o_137_noael_002"}
SCCS_vision_codex NOAEL =96 % - - - NOAEL study {"dose":"Statistical difference in total protein in BALF between high dose group Z-COTE® HP1 with controls not mentioned (high dose group 112.2 ± 8.7 vs control 79.6 ± 9.2 total protein).","effect":"______________________________________ 13 animals were used. Some explanation might have given insight to how and why this was done. Statistical difference in total protein in BALF between high dose group Z-COTE® HP1 with controls not mentioned (high dose group 112.2 ± 8.7 vs control 79.6 ± 9.2 total protein). The NOAEL derived by the study authors is based on both observations in BAL and lung histopathology occurring at the high dose group and not in mid dose group of 1.5 mg/m3. However, the SCCS concludes on a NOAEL of 0.3 mg/ m3 in view of the ongoing activation of lung macrophages and lung draining lymph nodes. 4. CONCLUSION The SCCS concludes that ZnO nanomaterials with the following characteristics can be considered similar to the ZnO nanomaterials as evaluated in opinion SCCS/1489/12 and thus pose no or limited risk for use on the skin as UV filter in sunscreen formulations: 1. ZnO nanoparticles of purity ≥96%, with wurtzite crystalline structure and physical appearance as clusters that are rod-like, star-like and/or","page":13,"pdf":"sccs_o_137.pdf","row_type":"noael_study","study_id":"sccs_o_137_noael_003"}
SCCS_vision_codex NOAEL =4 - - inhalation 90 days NOAEL study {"effect":". Other cosmetic ingredients can be used as coatings as long as they are demonstrated to the SCCS to be safe and do not affect the particle properties related to behaviour and/or effects, compared to the nanomaterials covered in the current opinion. 4. ZnO nanoparticles that have a comparable solubility to that reported in the dossier, i.e. below 50 mg/L (approximately the maximum solubility of the ZnO nanomaterials for which data are provided in the dossier). The submitted 90 days inhalation study resulted in a NOAEL of 0.3 mg/m3. However these new data do not address the concerns relating to the lung exposure and the potential manifestation of harmful effects. 5. MINORITY OPINION / 6. REFERENCES /","page":13,"pdf":"sccs_o_137.pdf","row_type":"noael_study","study_id":"sccs_o_137_noael_004"}
SCCS_vision_codex NOAEL =1000 mg/kg mouse oral - NOAEL study {"citation":"Reference: AR16)","dose":"hip, many effects were noted at the highest dose administered that should be considered dose related even when they only occur at the highest dose.","effect":"hip, many effects were noted at the highest dose administered that should be considered dose related even when they only occur at the highest dose. The pathological findings indicate a dose response relationship with the highest dose inducing the most severe alterations. The lowest dose investigated (1,000 mg/kg) also induced pathological effects in the animals. Most effects showed some minor differences between the 20 and 120 nm sized ZnO. Target organs for toxicity were liver, heart, spleen, pancreas and bone. A no observed adverse effect level (NOAEL) was not dentified because alterations were also observed at the lowest dose investigated (1,000 mg/kg). No deaths were observed in a similar study using a single oral dose of 5 mg/kg in mice (Reference: AR16). ZnO nanoparticles were approximately 50 nm in size (TEM evaluation), which were compared to ZnO microparticles showing at least one diameter >100 nm (TEM evaluation). DLS evaluation showed an average hydrodynamic diameter of 1,226 ± 120 nm for the ZnO microparticles, and an average hydrodynamic diame","page":29,"pdf":"sccs_o_103.pdf","row_type":"noael_study","study_id":"sccs_o_103_noael_001"}
SCCS_vision_codex NOAEL =1 mg/kg bw rat intravenous - repeated dose toxicity {"citation":"(References: 85, 94, 119)","dose":"In view of the indications for liver damage, a repeated dose toxicity study would have provided better information on potential toxicity.","effect":"toxic reactions were not observed. In view of the indications for liver damage, a repeated dose toxicity study would have provided better information on potential toxicity. In conclusion, after intravenous administration obtaining an internal dose of 5 mg/kg bw alterations in clinical pathology were observed that were indicative of liver damage. The liver damage appeared to be transient as similar alterations were not observed at four weeks after the single administration. Based on this study, the SCCS considers a NOAEL of 1 mg/kg bw for acute toxicity of ZnO in rats after intravenous administration. Additional studies submitted Additional information was included in the dossier on ZnO commercially obtained from Sigma-Aldrich and not related to the ZnO presented in the dossier. (References: 85, 94, 119)","page":86,"pdf":"sccs_o_103.pdf","row_type":"noael_study","study_id":"sccs_o_103_noael_003"}
SCCS_vision_codex NOAEL =2 % human oral 18 days repeated dose toxicity {"dose":"An NOAEL of 50 mg Zn2+/day was derived from a 10-week oral study with human volunteers and was used as a starting point for the risk characterization for repeated dose toxicity.","effect":"nc or zinc compounds is therefore chosen to be 2%. Based on the physical appearance, for dust exposure to zinc or zinc compounds a 10-fold lower default value of 0.2% is chosen in the risk assessment. For sunscreen containing 10% zinc oxide the following exposure assessment was performed: By an application of 9 g sunscreen/event, 3 events/day during 18 days/year the exposure will be 1,332 mg sunscreen/day, being 107 mg Zn2+/day. Assuming a dermal absorption of 2% the uptake is estimated to be 2.14 mg Zn2+/ day. An NOAEL of 50 mg Zn2+/day was derived from a 10-week oral study with human volunteers and was used as a starting point for the risk characterization for repeated dose toxicity. This NOAEL of 50 mg Zn2+/day results in an internal NOAEL of 10 mg Zn2+/day by correction for oral absorption (20%; worst case, because of the homeostasis the relative absorption will be smaller by excess of Zn2+-intake). Given that this study was with women (the most sensitive population in zinc supplementation studies), and that in women clinical","page":89,"pdf":"sccs_o_103.pdf","row_type":"noael_study","study_id":"sccs_o_103_noael_004"}
SCCS_vision_codex NOAEL =20 % human oral 18 days repeated dose toxicity {"dose":"An NOAEL of 50 mg Zn2+/day was derived from a 10-week oral study with human volunteers and was used as a starting point for the risk characterization for repeated dose toxicity.","effect":"the risk assessment. For sunscreen containing 10% zinc oxide the following exposure assessment was performed: By an application of 9 g sunscreen/event, 3 events/day during 18 days/year the exposure will be 1,332 mg sunscreen/day, being 107 mg Zn2+/day. Assuming a dermal absorption of 2% the uptake is estimated to be 2.14 mg Zn2+/ day. An NOAEL of 50 mg Zn2+/day was derived from a 10-week oral study with human volunteers and was used as a starting point for the risk characterization for repeated dose toxicity. This NOAEL of 50 mg Zn2+/day results in an internal NOAEL of 10 mg Zn2+/day by correction for oral absorption (20%; worst case, because of the homeostasis the relative absorption will be smaller by excess of Zn2+-intake). Given that this study was with women (the most sensitive population in zinc supplementation studies), and that in women clinical signs begin to appear only at a dose three times this NOAEL, a minimal MOS of 1 is considered sufficient when comparing the human NOAEL with the exposure levels for workers/consum","page":89,"pdf":"sccs_o_103.pdf","row_type":"noael_study","study_id":"sccs_o_103_noael_005"}
SCCS_vision_codex NOAEL =1 - human - - NOAEL study {"dose":"t this study was with women (the most sensitive population in zinc supplementation studies), and that in women clinical signs begin to appear only at a dose three times this NOAEL, a minimal MOS of 1 is considered sufficient when comparing the human NOAEL with the exposure levels for workers/consumers/general population.","effect":"t this study was with women (the most sensitive population in zinc supplementation studies), and that in women clinical signs begin to appear only at a dose three times this NOAEL, a minimal MOS of 1 is considered sufficient when comparing the human NOAEL with the exposure levels for workers/consumers/general population. The MOS between this internal NOAEL and the internal exposure as a result of exposure to sunscreen formulations is 5, which is a factor of 5 larger than the minimal MOS. The SCCS agrees with the NOAEL indicated in the RAR statement. Therefore, this information is used together with the data from the absorption study provided in the dossier and exposure assumptions from the SCCS Notes of Guidance for the risk assessment of zinc oxide nanoparticles in sun screens as follows:","page":89,"pdf":"sccs_o_103.pdf","row_type":"noael_study","study_id":"sccs_o_103_noael_010"}
SCCS_vision_codex NOAEL =0.0225 mg/kg bw/d human oral - NOAEL study {"citation":"Reference: 36) Amount absorbed/day (18,000 × 25%/100 × 0","dose":"36) Amount absorbed/day (18,000 × 25%/100 × 0.03%/100) 1.35 mg Typical body weight of human 60 kg Systemic exposure dose (1.35 mg/60 kg) 0.0225 mg/kg bw/d No Observed Adverse Effect Level NOAEL (oral, human, sensitive subpopulation)** 0.166 mg/kg bw/d Margin of Safety NOAEL/SED = 7.4 * Standard amount as indicated in the SCCS Notes of Guidance f...","effect":"inc oxide (nano form) ___________________________________________________________________________________________ 90 Calculation of the margin of safety for ZnO (nano) (See section 3.1.16 for the range of nano-ZnO covered by this opinion) Amount of sunscreen applied* 18,000 mg Maximum concentration of ZnO 25% Absorption through the skin 0.03% (Reference: 36) Amount absorbed/day (18,000 × 25%/100 × 0.03%/100) 1.35 mg Typical body weight of human 60 kg Systemic exposure dose (1.35 mg/60 kg) 0.0225 mg/kg bw/d No Observed Adverse Effect Level NOAEL (oral, human, sensitive subpopulation)** 0.166 mg/kg bw/d Margin of Safety NOAEL/SED = 7.4 * Standard amount as indicated in the SCCS Notes of Guidance for the testing of cosmetic ingredients and their safety evaluation SCCS/1416/11 ** The internal NOAEL for ZnO is 10 mg Zn2+/day = 10/60= 0.166 mg /kg bw per day (Reference 44, sub III) The calculation of the exposure via sun protection products to ZnO nanoparticles assuming Zn2+ uptake results in a MoS of 7.4. Given that the NOAEL is derived from a study on","page":90,"pdf":"sccs_o_103.pdf","row_type":"noael_study","study_id":"sccs_o_103_noael_011"}
SCCS_vision_codex NOAEL =0.166 mg/kg bw/d human oral - NOAEL study {"citation":"Reference: 36) Amount absorbed/day (18,000 × 25%/100 × 0","dose":"36) Amount absorbed/day (18,000 × 25%/100 × 0.03%/100) 1.35 mg Typical body weight of human 60 kg Systemic exposure dose (1.35 mg/60 kg) 0.0225 mg/kg bw/d No Observed Adverse Effect Level NOAEL (oral, human, sensitive subpopulation)** 0.166 mg/kg bw/d Margin of Safety NOAEL/SED = 7.4 * Standard amount as indicated in the SCCS Notes of Guidance f...","effect":"________________________________________________________________________________ 90 Calculation of the margin of safety for ZnO (nano) (See section 3.1.16 for the range of nano-ZnO covered by this opinion) Amount of sunscreen applied* 18,000 mg Maximum concentration of ZnO 25% Absorption through the skin 0.03% (Reference: 36) Amount absorbed/day (18,000 × 25%/100 × 0.03%/100) 1.35 mg Typical body weight of human 60 kg Systemic exposure dose (1.35 mg/60 kg) 0.0225 mg/kg bw/d No Observed Adverse Effect Level NOAEL (oral, human, sensitive subpopulation)** 0.166 mg/kg bw/d Margin of Safety NOAEL/SED = 7.4 * Standard amount as indicated in the SCCS Notes of Guidance for the testing of cosmetic ingredients and their safety evaluation SCCS/1416/11 ** The internal NOAEL for ZnO is 10 mg Zn2+/day = 10/60= 0.166 mg /kg bw per day (Reference 44, sub III) The calculation of the exposure via sun protection products to ZnO nanoparticles assuming Zn2+ uptake results in a MoS of 7.4. Given that the NOAEL is derived from a study on women","page":90,"pdf":"sccs_o_103.pdf","row_type":"noael_study","study_id":"sccs_o_103_noael_012"}
SCCS_vision_codex NOAEL =0.9 mg/kg/d human oral - NOAEL study {"citation":"(Reference 44, sub III)","dose":"CS/1416/11 ** The internal NOAEL for ZnO is 10 mg Zn2+/day = 10/60= 0.166 mg /kg bw per day (Reference 44, sub III) The calculation of the exposure via sun protection products to ZnO nanoparticles assuming Zn2+ uptake results in a MoS of 7.4.","effect":"CS/1416/11 ** The internal NOAEL for ZnO is 10 mg Zn2+/day = 10/60= 0.166 mg /kg bw per day (Reference 44, sub III) The calculation of the exposure via sun protection products to ZnO nanoparticles assuming Zn2+ uptake results in a MoS of 7.4. Given that the NOAEL is derived from a study on women (the most sensitive population in zinc supplementation studies), and that in women clinical signs begin to appear only at a dose three times this NOAEL, a minimal MOS of 1 is considered sufficient when comparing the human NOAEL with the exposure levels for workers/consumers/general population (Reference 44, sub III). Calculation of the Margin of Safety for Lip products According to the SCCS Notes of Guidance for the testing of cosmetic ingredients and their safety evaluation (SCCS/1416/11) the daily exposure to lipstick/lipproducts is 0.9 mg/kg/d. Exposure dose (0.9 x 25%) 0.225 mg/kg bw/day. No Observed Adverse Effect Level NOAEL (oral, human)* 0.83 mg/kg bw/d Margin of Safety NOAEL/ED** = 3.7 * The NOAEL for ZnO is 50 mg Zn2+/day =","page":90,"pdf":"sccs_o_103.pdf","row_type":"noael_study","study_id":"sccs_o_103_noael_017"}
SCCS_vision_codex NOAEL =0.225 mg/kg bw/day human oral - NOAEL study {"citation":"(Reference 44, sub III)","dose":"clinical signs begin to appear only at a dose three times this NOAEL, a minimal MOS of 1 is considered sufficient when comparing the human NOAEL with the exposure levels for workers/consumers/general population (Reference 44, sub III).","effect":"clinical signs begin to appear only at a dose three times this NOAEL, a minimal MOS of 1 is considered sufficient when comparing the human NOAEL with the exposure levels for workers/consumers/general population (Reference 44, sub III). Calculation of the Margin of Safety for Lip products According to the SCCS Notes of Guidance for the testing of cosmetic ingredients and their safety evaluation (SCCS/1416/11) the daily exposure to lipstick/lipproducts is 0.9 mg/kg/d. Exposure dose (0.9 x 25%) 0.225 mg/kg bw/day. No Observed Adverse Effect Level NOAEL (oral, human)* 0.83 mg/kg bw/d Margin of Safety NOAEL/ED** = 3.7 * The NOAEL for ZnO is 50 mg Zn2+/day = 50/60= 0.83 mg /kg bw per day (Reference 44, sub III) ** Since route to route extrapolation is not needed, the (external) NOAEL is compared to the (external) exposure dose It is expected that the exposure to lipstick/lip products that contain high SPF factors (eg ZnO nanomaterial) is less than the exposure to ‘regular’ lipstick/lip products. Typically, these products are used only in specific time fram","page":90,"pdf":"sccs_o_103.pdf","row_type":"noael_study","study_id":"sccs_o_103_noael_018"}
SCCS_vision_codex NOAEL =0.83 mg/kg bw/d human oral - NOAEL study {"citation":"(Reference 44, sub III)","dose":"nly at a dose three times this NOAEL, a minimal MOS of 1 is considered sufficient when comparing the human NOAEL with the exposure levels for workers/consumers/general population (Reference 44, sub III).","effect":"nly at a dose three times this NOAEL, a minimal MOS of 1 is considered sufficient when comparing the human NOAEL with the exposure levels for workers/consumers/general population (Reference 44, sub III). Calculation of the Margin of Safety for Lip products According to the SCCS Notes of Guidance for the testing of cosmetic ingredients and their safety evaluation (SCCS/1416/11) the daily exposure to lipstick/lipproducts is 0.9 mg/kg/d. Exposure dose (0.9 x 25%) 0.225 mg/kg bw/day. No Observed Adverse Effect Level NOAEL (oral, human)* 0.83 mg/kg bw/d Margin of Safety NOAEL/ED** = 3.7 * The NOAEL for ZnO is 50 mg Zn2+/day = 50/60= 0.83 mg /kg bw per day (Reference 44, sub III) ** Since route to route extrapolation is not needed, the (external) NOAEL is compared to the (external) exposure dose It is expected that the exposure to lipstick/lip products that contain high SPF factors (eg ZnO nanomaterial) is less than the exposure to ‘regular’ lipstick/lip products. Typically, these products are used only in specific time frames, e.","page":90,"pdf":"sccs_o_103.pdf","row_type":"noael_study","study_id":"sccs_o_103_noael_019"}
SCCS_vision_codex NOAEL =50 - mouse oral - NOAEL study {"citation":"(Reference 44, sub III)","dose":"However, no differences weren observed between ZnO administered as nanoscale or microscale particles.","effect":"ure In one exploratory study in mice, systemic availability of Zn was indicated after a single oral exposure. However, no differences weren observed between ZnO administered as nanoscale or microscale particles. It is likely that absorbed Zn in the GI-tract was in the dissolved ionic form. In view of the data provided, oral exposure of nano-ZnO via applications of nano-ZnO as a cosmetic ingredient in sunscreens should be considered to be of a similar risk to micron-sized ZnO as previously evaluated in the RAR. The NOAEL for oral intake of ZnO is 50 mg /bw day (Reference 44, sub III). The oral exposure to ZnO nanoparticles as cosmetic ingredient in sunscreens is limited to accidental ingestion of small fractions of lip products and sun protection products and can be considered to be low. Inhalation exposure Upon inhalation of ZnO nanoparticles, serious local effects in the lung were observed. Even if this may be due to the solubilized Zn ions, the effects are a direct result of the exposure to the ZnO nanoparticles. Therefore, th","page":96,"pdf":"sccs_o_103.pdf","row_type":"noael_study","study_id":"sccs_o_103_noael_023"}
SCCS_vision_codex NOAEL =90 - - inhalation 90 days NOAEL study {"dose":"Conclusions The study authors concluded that transient local effects on the respiratory tract were only observed in the highest dose group for this 90 days inhalation study.","effect":"upporting the rapid elimination. In the study four animals were found dead or killed moribund, the cause of death being in two animals a purulent and necrotizing inflammation of the urogenital organs, in one animal due to a pronounced malignant lymphoma, and in one animal due to unknown cause. These observations were not treatment related. Conclusions The study authors concluded that transient local effects on the respiratory tract were only observed in the highest dose group for this 90 days inhalation study. A NOAEL of 1.5 g/m³ can be identified for the test item Z-COTE® HP1. Under the conditions of this test no persistent toxicity was found and all lesions were found to be recovered within the 28 day post exposure period. SCCS comments The file received for the study report was not signed by the study director and/or scientists involved. The report was supposedly to be published by the end of 2012, however, it was not found on Cefic website (June 2013). Size distributions of both nano- and micron-sized ZnO particles used","page":12,"pdf":"sccs_o_137.pdf","row_type":"noael_study","study_id":"sccs_o_137_noael_001"}
SCCS_vision_codex NOAEL =1518 - - - - NOAEL study {"dose":"Statistical difference in total protein in BALF between high dose group Z-COTE® HP1 with controls not mentioned (high dose group 112.2 ± 8.7 vs control 79.6 ± 9.2 total protein).","effect":"SCCS/1518/13 Revision of the addendum to the opinion on zinc oxide (nano form) ___________________________________________________________________________________________ 13 animals were used. Some explanation might have given insight to how and why this was done. Statistical difference in total protein in BALF between high dose group Z-COTE® HP1 with controls not mentioned (high dose group 112.2 ± 8.7 vs control 79.6 ± 9.2 total protein). The NOAEL derived by the study authors is based on both observations in BAL and lung histopathology occurring at the high dose group and not in mid dose group of 1.5 mg/m3. However, the SCCS concludes on a NOAEL of 0.3 mg/ m3 in view of the ongoing activation of lung macrophages and lung draining lymph nodes. 4. CONCLUSION The SCCS concludes that ZnO nanomaterials with the following characteristics can be considered similar to the ZnO nanomaterials as evaluated in opinion SCCS/1489/12 and thus pose no or limited risk for","page":13,"pdf":"sccs_o_137.pdf","row_type":"noael_study","study_id":"sccs_o_137_noael_002"}
SCCS_vision_codex NOAEL =96 % - - - NOAEL study {"dose":"Statistical difference in total protein in BALF between high dose group Z-COTE® HP1 with controls not mentioned (high dose group 112.2 ± 8.7 vs control 79.6 ± 9.2 total protein).","effect":"______________________________________ 13 animals were used. Some explanation might have given insight to how and why this was done. Statistical difference in total protein in BALF between high dose group Z-COTE® HP1 with controls not mentioned (high dose group 112.2 ± 8.7 vs control 79.6 ± 9.2 total protein). The NOAEL derived by the study authors is based on both observations in BAL and lung histopathology occurring at the high dose group and not in mid dose group of 1.5 mg/m3. However, the SCCS concludes on a NOAEL of 0.3 mg/ m3 in view of the ongoing activation of lung macrophages and lung draining lymph nodes. 4. CONCLUSION The SCCS concludes that ZnO nanomaterials with the following characteristics can be considered similar to the ZnO nanomaterials as evaluated in opinion SCCS/1489/12 and thus pose no or limited risk for use on the skin as UV filter in sunscreen formulations: 1. ZnO nanoparticles of purity ≥96%, with wurtzite crystalline structure and physical appearance as clusters that are rod-like, star-like and/or","page":13,"pdf":"sccs_o_137.pdf","row_type":"noael_study","study_id":"sccs_o_137_noael_003"}
SCCS_vision_codex NOAEL =4 - - inhalation 90 days NOAEL study {"effect":". Other cosmetic ingredients can be used as coatings as long as they are demonstrated to the SCCS to be safe and do not affect the particle properties related to behaviour and/or effects, compared to the nanomaterials covered in the current opinion. 4. ZnO nanoparticles that have a comparable solubility to that reported in the dossier, i.e. below 50 mg/L (approximately the maximum solubility of the ZnO nanomaterials for which data are provided in the dossier). The submitted 90 days inhalation study resulted in a NOAEL of 0.3 mg/m3. However these new data do not address the concerns relating to the lung exposure and the potential manifestation of harmful effects. 5. MINORITY OPINION / 6. REFERENCES /","page":13,"pdf":"sccs_o_137.pdf","row_type":"noael_study","study_id":"sccs_o_137_noael_004"}
SCCS_vision_codex NOAEL =1000 mg/kg mouse oral - NOAEL study {"citation":"Reference: AR16)","dose":"hip, many effects were noted at the highest dose administered that should be considered dose related even when they only occur at the highest dose.","effect":"hip, many effects were noted at the highest dose administered that should be considered dose related even when they only occur at the highest dose. The pathological findings indicate a dose response relationship with the highest dose inducing the most severe alterations. The lowest dose investigated (1,000 mg/kg) also induced pathological effects in the animals. Most effects showed some minor differences between the 20 and 120 nm sized ZnO. Target organs for toxicity were liver, heart, spleen, pancreas and bone. A no observed adverse effect level (NOAEL) was not dentified because alterations were also observed at the lowest dose investigated (1,000 mg/kg). No deaths were observed in a similar study using a single oral dose of 5 mg/kg in mice (Reference: AR16). ZnO nanoparticles were approximately 50 nm in size (TEM evaluation), which were compared to ZnO microparticles showing at least one diameter >100 nm (TEM evaluation). DLS evaluation showed an average hydrodynamic diameter of 1,226 ± 120 nm for the ZnO microparticles, and an average hydrodynamic diame","page":29,"pdf":"sccs_o_103.pdf","row_type":"noael_study","study_id":"sccs_o_103_noael_001"}
SCCS_vision_codex NOAEL =1 mg/kg bw rat intravenous - repeated dose toxicity {"citation":"(References: 85, 94, 119)","dose":"In view of the indications for liver damage, a repeated dose toxicity study would have provided better information on potential toxicity.","effect":"toxic reactions were not observed. In view of the indications for liver damage, a repeated dose toxicity study would have provided better information on potential toxicity. In conclusion, after intravenous administration obtaining an internal dose of 5 mg/kg bw alterations in clinical pathology were observed that were indicative of liver damage. The liver damage appeared to be transient as similar alterations were not observed at four weeks after the single administration. Based on this study, the SCCS considers a NOAEL of 1 mg/kg bw for acute toxicity of ZnO in rats after intravenous administration. Additional studies submitted Additional information was included in the dossier on ZnO commercially obtained from Sigma-Aldrich and not related to the ZnO presented in the dossier. (References: 85, 94, 119)","page":86,"pdf":"sccs_o_103.pdf","row_type":"noael_study","study_id":"sccs_o_103_noael_003"}
SCCS_vision_codex NOAEL =2 % human oral 18 days repeated dose toxicity {"dose":"An NOAEL of 50 mg Zn2+/day was derived from a 10-week oral study with human volunteers and was used as a starting point for the risk characterization for repeated dose toxicity.","effect":"nc or zinc compounds is therefore chosen to be 2%. Based on the physical appearance, for dust exposure to zinc or zinc compounds a 10-fold lower default value of 0.2% is chosen in the risk assessment. For sunscreen containing 10% zinc oxide the following exposure assessment was performed: By an application of 9 g sunscreen/event, 3 events/day during 18 days/year the exposure will be 1,332 mg sunscreen/day, being 107 mg Zn2+/day. Assuming a dermal absorption of 2% the uptake is estimated to be 2.14 mg Zn2+/ day. An NOAEL of 50 mg Zn2+/day was derived from a 10-week oral study with human volunteers and was used as a starting point for the risk characterization for repeated dose toxicity. This NOAEL of 50 mg Zn2+/day results in an internal NOAEL of 10 mg Zn2+/day by correction for oral absorption (20%; worst case, because of the homeostasis the relative absorption will be smaller by excess of Zn2+-intake). Given that this study was with women (the most sensitive population in zinc supplementation studies), and that in women clinical","page":89,"pdf":"sccs_o_103.pdf","row_type":"noael_study","study_id":"sccs_o_103_noael_004"}
SCCS_vision_codex NOAEL =20 % human oral 18 days repeated dose toxicity {"dose":"An NOAEL of 50 mg Zn2+/day was derived from a 10-week oral study with human volunteers and was used as a starting point for the risk characterization for repeated dose toxicity.","effect":"the risk assessment. For sunscreen containing 10% zinc oxide the following exposure assessment was performed: By an application of 9 g sunscreen/event, 3 events/day during 18 days/year the exposure will be 1,332 mg sunscreen/day, being 107 mg Zn2+/day. Assuming a dermal absorption of 2% the uptake is estimated to be 2.14 mg Zn2+/ day. An NOAEL of 50 mg Zn2+/day was derived from a 10-week oral study with human volunteers and was used as a starting point for the risk characterization for repeated dose toxicity. This NOAEL of 50 mg Zn2+/day results in an internal NOAEL of 10 mg Zn2+/day by correction for oral absorption (20%; worst case, because of the homeostasis the relative absorption will be smaller by excess of Zn2+-intake). Given that this study was with women (the most sensitive population in zinc supplementation studies), and that in women clinical signs begin to appear only at a dose three times this NOAEL, a minimal MOS of 1 is considered sufficient when comparing the human NOAEL with the exposure levels for workers/consum","page":89,"pdf":"sccs_o_103.pdf","row_type":"noael_study","study_id":"sccs_o_103_noael_005"}
SCCS_vision_codex NOAEL =1 - human - - NOAEL study {"dose":"t this study was with women (the most sensitive population in zinc supplementation studies), and that in women clinical signs begin to appear only at a dose three times this NOAEL, a minimal MOS of 1 is considered sufficient when comparing the human NOAEL with the exposure levels for workers/consumers/general population.","effect":"t this study was with women (the most sensitive population in zinc supplementation studies), and that in women clinical signs begin to appear only at a dose three times this NOAEL, a minimal MOS of 1 is considered sufficient when comparing the human NOAEL with the exposure levels for workers/consumers/general population. The MOS between this internal NOAEL and the internal exposure as a result of exposure to sunscreen formulations is 5, which is a factor of 5 larger than the minimal MOS. The SCCS agrees with the NOAEL indicated in the RAR statement. Therefore, this information is used together with the data from the absorption study provided in the dossier and exposure assumptions from the SCCS Notes of Guidance for the risk assessment of zinc oxide nanoparticles in sun screens as follows:","page":89,"pdf":"sccs_o_103.pdf","row_type":"noael_study","study_id":"sccs_o_103_noael_010"}
SCCS_vision_codex NOAEL =0.0225 mg/kg bw/d human oral - NOAEL study {"citation":"Reference: 36) Amount absorbed/day (18,000 × 25%/100 × 0","dose":"36) Amount absorbed/day (18,000 × 25%/100 × 0.03%/100) 1.35 mg Typical body weight of human 60 kg Systemic exposure dose (1.35 mg/60 kg) 0.0225 mg/kg bw/d No Observed Adverse Effect Level NOAEL (oral, human, sensitive subpopulation)** 0.166 mg/kg bw/d Margin of Safety NOAEL/SED = 7.4 * Standard amount as indicated in the SCCS Notes of Guidance f...","effect":"inc oxide (nano form) ___________________________________________________________________________________________ 90 Calculation of the margin of safety for ZnO (nano) (See section 3.1.16 for the range of nano-ZnO covered by this opinion) Amount of sunscreen applied* 18,000 mg Maximum concentration of ZnO 25% Absorption through the skin 0.03% (Reference: 36) Amount absorbed/day (18,000 × 25%/100 × 0.03%/100) 1.35 mg Typical body weight of human 60 kg Systemic exposure dose (1.35 mg/60 kg) 0.0225 mg/kg bw/d No Observed Adverse Effect Level NOAEL (oral, human, sensitive subpopulation)** 0.166 mg/kg bw/d Margin of Safety NOAEL/SED = 7.4 * Standard amount as indicated in the SCCS Notes of Guidance for the testing of cosmetic ingredients and their safety evaluation SCCS/1416/11 ** The internal NOAEL for ZnO is 10 mg Zn2+/day = 10/60= 0.166 mg /kg bw per day (Reference 44, sub III) The calculation of the exposure via sun protection products to ZnO nanoparticles assuming Zn2+ uptake results in a MoS of 7.4. Given that the NOAEL is derived from a study on","page":90,"pdf":"sccs_o_103.pdf","row_type":"noael_study","study_id":"sccs_o_103_noael_011"}
SCCS_vision_codex NOAEL =0.166 mg/kg bw/d human oral - NOAEL study {"citation":"Reference: 36) Amount absorbed/day (18,000 × 25%/100 × 0","dose":"36) Amount absorbed/day (18,000 × 25%/100 × 0.03%/100) 1.35 mg Typical body weight of human 60 kg Systemic exposure dose (1.35 mg/60 kg) 0.0225 mg/kg bw/d No Observed Adverse Effect Level NOAEL (oral, human, sensitive subpopulation)** 0.166 mg/kg bw/d Margin of Safety NOAEL/SED = 7.4 * Standard amount as indicated in the SCCS Notes of Guidance f...","effect":"________________________________________________________________________________ 90 Calculation of the margin of safety for ZnO (nano) (See section 3.1.16 for the range of nano-ZnO covered by this opinion) Amount of sunscreen applied* 18,000 mg Maximum concentration of ZnO 25% Absorption through the skin 0.03% (Reference: 36) Amount absorbed/day (18,000 × 25%/100 × 0.03%/100) 1.35 mg Typical body weight of human 60 kg Systemic exposure dose (1.35 mg/60 kg) 0.0225 mg/kg bw/d No Observed Adverse Effect Level NOAEL (oral, human, sensitive subpopulation)** 0.166 mg/kg bw/d Margin of Safety NOAEL/SED = 7.4 * Standard amount as indicated in the SCCS Notes of Guidance for the testing of cosmetic ingredients and their safety evaluation SCCS/1416/11 ** The internal NOAEL for ZnO is 10 mg Zn2+/day = 10/60= 0.166 mg /kg bw per day (Reference 44, sub III) The calculation of the exposure via sun protection products to ZnO nanoparticles assuming Zn2+ uptake results in a MoS of 7.4. Given that the NOAEL is derived from a study on women","page":90,"pdf":"sccs_o_103.pdf","row_type":"noael_study","study_id":"sccs_o_103_noael_012"}
SCCS_vision_codex NOAEL =0.9 mg/kg/d human oral - NOAEL study {"citation":"(Reference 44, sub III)","dose":"CS/1416/11 ** The internal NOAEL for ZnO is 10 mg Zn2+/day = 10/60= 0.166 mg /kg bw per day (Reference 44, sub III) The calculation of the exposure via sun protection products to ZnO nanoparticles assuming Zn2+ uptake results in a MoS of 7.4.","effect":"CS/1416/11 ** The internal NOAEL for ZnO is 10 mg Zn2+/day = 10/60= 0.166 mg /kg bw per day (Reference 44, sub III) The calculation of the exposure via sun protection products to ZnO nanoparticles assuming Zn2+ uptake results in a MoS of 7.4. Given that the NOAEL is derived from a study on women (the most sensitive population in zinc supplementation studies), and that in women clinical signs begin to appear only at a dose three times this NOAEL, a minimal MOS of 1 is considered sufficient when comparing the human NOAEL with the exposure levels for workers/consumers/general population (Reference 44, sub III). Calculation of the Margin of Safety for Lip products According to the SCCS Notes of Guidance for the testing of cosmetic ingredients and their safety evaluation (SCCS/1416/11) the daily exposure to lipstick/lipproducts is 0.9 mg/kg/d. Exposure dose (0.9 x 25%) 0.225 mg/kg bw/day. No Observed Adverse Effect Level NOAEL (oral, human)* 0.83 mg/kg bw/d Margin of Safety NOAEL/ED** = 3.7 * The NOAEL for ZnO is 50 mg Zn2+/day =","page":90,"pdf":"sccs_o_103.pdf","row_type":"noael_study","study_id":"sccs_o_103_noael_017"}
SCCS_vision_codex NOAEL =0.225 mg/kg bw/day human oral - NOAEL study {"citation":"(Reference 44, sub III)","dose":"clinical signs begin to appear only at a dose three times this NOAEL, a minimal MOS of 1 is considered sufficient when comparing the human NOAEL with the exposure levels for workers/consumers/general population (Reference 44, sub III).","effect":"clinical signs begin to appear only at a dose three times this NOAEL, a minimal MOS of 1 is considered sufficient when comparing the human NOAEL with the exposure levels for workers/consumers/general population (Reference 44, sub III). Calculation of the Margin of Safety for Lip products According to the SCCS Notes of Guidance for the testing of cosmetic ingredients and their safety evaluation (SCCS/1416/11) the daily exposure to lipstick/lipproducts is 0.9 mg/kg/d. Exposure dose (0.9 x 25%) 0.225 mg/kg bw/day. No Observed Adverse Effect Level NOAEL (oral, human)* 0.83 mg/kg bw/d Margin of Safety NOAEL/ED** = 3.7 * The NOAEL for ZnO is 50 mg Zn2+/day = 50/60= 0.83 mg /kg bw per day (Reference 44, sub III) ** Since route to route extrapolation is not needed, the (external) NOAEL is compared to the (external) exposure dose It is expected that the exposure to lipstick/lip products that contain high SPF factors (eg ZnO nanomaterial) is less than the exposure to ‘regular’ lipstick/lip products. Typically, these products are used only in specific time fram","page":90,"pdf":"sccs_o_103.pdf","row_type":"noael_study","study_id":"sccs_o_103_noael_018"}
SCCS_vision_codex NOAEL =0.83 mg/kg bw/d human oral - NOAEL study {"citation":"(Reference 44, sub III)","dose":"nly at a dose three times this NOAEL, a minimal MOS of 1 is considered sufficient when comparing the human NOAEL with the exposure levels for workers/consumers/general population (Reference 44, sub III).","effect":"nly at a dose three times this NOAEL, a minimal MOS of 1 is considered sufficient when comparing the human NOAEL with the exposure levels for workers/consumers/general population (Reference 44, sub III). Calculation of the Margin of Safety for Lip products According to the SCCS Notes of Guidance for the testing of cosmetic ingredients and their safety evaluation (SCCS/1416/11) the daily exposure to lipstick/lipproducts is 0.9 mg/kg/d. Exposure dose (0.9 x 25%) 0.225 mg/kg bw/day. No Observed Adverse Effect Level NOAEL (oral, human)* 0.83 mg/kg bw/d Margin of Safety NOAEL/ED** = 3.7 * The NOAEL for ZnO is 50 mg Zn2+/day = 50/60= 0.83 mg /kg bw per day (Reference 44, sub III) ** Since route to route extrapolation is not needed, the (external) NOAEL is compared to the (external) exposure dose It is expected that the exposure to lipstick/lip products that contain high SPF factors (eg ZnO nanomaterial) is less than the exposure to ‘regular’ lipstick/lip products. Typically, these products are used only in specific time frames, e.","page":90,"pdf":"sccs_o_103.pdf","row_type":"noael_study","study_id":"sccs_o_103_noael_019"}
SCCS_vision_codex NOAEL =50 - mouse oral - NOAEL study {"citation":"(Reference 44, sub III)","dose":"However, no differences weren observed between ZnO administered as nanoscale or microscale particles.","effect":"ure In one exploratory study in mice, systemic availability of Zn was indicated after a single oral exposure. However, no differences weren observed between ZnO administered as nanoscale or microscale particles. It is likely that absorbed Zn in the GI-tract was in the dissolved ionic form. In view of the data provided, oral exposure of nano-ZnO via applications of nano-ZnO as a cosmetic ingredient in sunscreens should be considered to be of a similar risk to micron-sized ZnO as previously evaluated in the RAR. The NOAEL for oral intake of ZnO is 50 mg /bw day (Reference 44, sub III). The oral exposure to ZnO nanoparticles as cosmetic ingredient in sunscreens is limited to accidental ingestion of small fractions of lip products and sun protection products and can be considered to be low. Inhalation exposure Upon inhalation of ZnO nanoparticles, serious local effects in the lung were observed. Even if this may be due to the solubilized Zn ions, the effects are a direct result of the exposure to the ZnO nanoparticles. Therefore, th","page":96,"pdf":"sccs_o_103.pdf","row_type":"noael_study","study_id":"sccs_o_103_noael_023"}
SCCS_vision_codex NOAEL =90 - - inhalation 90 days NOAEL study {"dose":"Conclusions The study authors concluded that transient local effects on the respiratory tract were only observed in the highest dose group for this 90 days inhalation study.","effect":"upporting the rapid elimination. In the study four animals were found dead or killed moribund, the cause of death being in two animals a purulent and necrotizing inflammation of the urogenital organs, in one animal due to a pronounced malignant lymphoma, and in one animal due to unknown cause. These observations were not treatment related. Conclusions The study authors concluded that transient local effects on the respiratory tract were only observed in the highest dose group for this 90 days inhalation study. A NOAEL of 1.5 g/m³ can be identified for the test item Z-COTE® HP1. Under the conditions of this test no persistent toxicity was found and all lesions were found to be recovered within the 28 day post exposure period. SCCS comments The file received for the study report was not signed by the study director and/or scientists involved. The report was supposedly to be published by the end of 2012, however, it was not found on Cefic website (June 2013). Size distributions of both nano- and micron-sized ZnO particles used","page":12,"pdf":"sccs_o_137.pdf","row_type":"noael_study","study_id":"sccs_o_137_noael_001"}
SCCS_vision_codex NOAEL =1518 - - - - NOAEL study {"dose":"Statistical difference in total protein in BALF between high dose group Z-COTE® HP1 with controls not mentioned (high dose group 112.2 ± 8.7 vs control 79.6 ± 9.2 total protein).","effect":"SCCS/1518/13 Revision of the addendum to the opinion on zinc oxide (nano form) ___________________________________________________________________________________________ 13 animals were used. Some explanation might have given insight to how and why this was done. Statistical difference in total protein in BALF between high dose group Z-COTE® HP1 with controls not mentioned (high dose group 112.2 ± 8.7 vs control 79.6 ± 9.2 total protein). The NOAEL derived by the study authors is based on both observations in BAL and lung histopathology occurring at the high dose group and not in mid dose group of 1.5 mg/m3. However, the SCCS concludes on a NOAEL of 0.3 mg/ m3 in view of the ongoing activation of lung macrophages and lung draining lymph nodes. 4. CONCLUSION The SCCS concludes that ZnO nanomaterials with the following characteristics can be considered similar to the ZnO nanomaterials as evaluated in opinion SCCS/1489/12 and thus pose no or limited risk for","page":13,"pdf":"sccs_o_137.pdf","row_type":"noael_study","study_id":"sccs_o_137_noael_002"}
SCCS_vision_codex NOAEL =96 % - - - NOAEL study {"dose":"Statistical difference in total protein in BALF between high dose group Z-COTE® HP1 with controls not mentioned (high dose group 112.2 ± 8.7 vs control 79.6 ± 9.2 total protein).","effect":"______________________________________ 13 animals were used. Some explanation might have given insight to how and why this was done. Statistical difference in total protein in BALF between high dose group Z-COTE® HP1 with controls not mentioned (high dose group 112.2 ± 8.7 vs control 79.6 ± 9.2 total protein). The NOAEL derived by the study authors is based on both observations in BAL and lung histopathology occurring at the high dose group and not in mid dose group of 1.5 mg/m3. However, the SCCS concludes on a NOAEL of 0.3 mg/ m3 in view of the ongoing activation of lung macrophages and lung draining lymph nodes. 4. CONCLUSION The SCCS concludes that ZnO nanomaterials with the following characteristics can be considered similar to the ZnO nanomaterials as evaluated in opinion SCCS/1489/12 and thus pose no or limited risk for use on the skin as UV filter in sunscreen formulations: 1. ZnO nanoparticles of purity ≥96%, with wurtzite crystalline structure and physical appearance as clusters that are rod-like, star-like and/or","page":13,"pdf":"sccs_o_137.pdf","row_type":"noael_study","study_id":"sccs_o_137_noael_003"}
SCCS_vision_codex NOAEL =4 - - inhalation 90 days NOAEL study {"effect":". Other cosmetic ingredients can be used as coatings as long as they are demonstrated to the SCCS to be safe and do not affect the particle properties related to behaviour and/or effects, compared to the nanomaterials covered in the current opinion. 4. ZnO nanoparticles that have a comparable solubility to that reported in the dossier, i.e. below 50 mg/L (approximately the maximum solubility of the ZnO nanomaterials for which data are provided in the dossier). The submitted 90 days inhalation study resulted in a NOAEL of 0.3 mg/m3. However these new data do not address the concerns relating to the lung exposure and the potential manifestation of harmful effects. 5. MINORITY OPINION / 6. REFERENCES /","page":13,"pdf":"sccs_o_137.pdf","row_type":"noael_study","study_id":"sccs_o_137_noael_004"}
ToxValDB_DOE_Wildlife_Benchmarks 2 endpoints
Source Endpoint Type Value Unit Species Route Duration Study Type Reference
ToxValDB_DOE_Wildlife_Benchmarks LOAEL =320 mg/kg bw/day Rat oral - repeat dose other STORED_SOURCE_RECORD=https://clowder.edap-cluster.com/files/65bd1d53e4b063812d68c240; RECORD_SOURCE_LEVEL=Extraction document; SOURCE_URL=https://rais.ornl.gov/documents/tm86r3.pdf; STUDY_GROUP=DOE Wildlife Benchmarks_dup_-_15511732_15511733:-:--; 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_3ebf403078a5e913b57b05bc20466670
ToxValDB_DOE_Wildlife_Benchmarks NOAEL =160 mg/kg bw/day Rat oral - repeat dose other STORED_SOURCE_RECORD=https://clowder.edap-cluster.com/files/65bd1d53e4b063812d68c240; RECORD_SOURCE_LEVEL=Extraction document; SOURCE_URL=https://rais.ornl.gov/documents/tm86r3.pdf; STUDY_GROUP=DOE Wildlife Benchmarks_dup_-_15511732_15511733:-:--; 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_5842136dc14ffb68cb0f57e51d356058
ToxValDB_ECHA_IUCLID 12 endpoints
Source Endpoint Type Value Unit Species Route Duration Study Type Reference
ToxValDB_ECHA_IUCLID LEL =2.5 mg/m3 Rat inhalation - acute QUALITY=2 (reliable with restrictions); STORED_SOURCE_RECORD=https://clowder.edap-cluster.com/files/67c61b61e4b096bca876de2f; RECORD_SOURCE_LEVEL=Extraction document; SOURCE_URL=https://echa.europa.eu/; SUBSOURCE_URL=https://echa.europa.eu/registration-dossier/-/registered-dossier/10228/7/3/3?documentUUID=819bf807-93be-4ebf-8cda-44ec703048cc; YEAR=1969; ORIGINAL_YEAR=1969; STUDY_GROUP=ECHA IUCLID:15795745: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_ab3ff196fb47d292a28ee1e5d0bcd425
ToxValDB_ECHA_IUCLID LEL =7.8 mg/m3 Guinea Pig inhalation - acute QUALITY=2 (reliable with restrictions); STORED_SOURCE_RECORD=https://clowder.edap-cluster.com/files/66059759e4b063812d6fa6de; RECORD_SOURCE_LEVEL=Extraction document; SOURCE_URL=https://echa.europa.eu/; SUBSOURCE_URL=https://echa.europa.eu/registration-dossier/-/registered-dossier/10329/7/3/3?documentUUID=9335e422-4b04-439e-b32c-4a913c2da116; YEAR=2013; ORIGINAL_YEAR=2013; STUDY_GROUP=ECHA IUCLID_dup_Acute Toxicity Inhalation_15795975_15796897: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_084b71e7b0617cdc7e06127d20f0ba17
ToxValDB_ECHA_IUCLID LEL =5 mg/m3 Rabbit inhalation - acute QUALITY=2 (reliable with restrictions); STORED_SOURCE_RECORD=https://clowder.edap-cluster.com/files/66059759e4b063812d6fa6de; RECORD_SOURCE_LEVEL=Extraction document; SOURCE_URL=https://echa.europa.eu/; SUBSOURCE_URL=https://echa.europa.eu/registration-dossier/-/registered-dossier/11214/7/3/3?documentUUID=fcaa6bea-650a-413b-94a6-3d002945fc60; YEAR=1982; ORIGINAL_YEAR=1982; STUDY_GROUP=ECHA IUCLID:15796094: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_4cd11eedad53117f0d834ca188afbb0c
ToxValDB_ECHA_IUCLID LEL ~4.6 mg/m3 Guinea Pig inhalation short-term; 6 days short-term QUALITY=2 (reliable with restrictions); STORED_SOURCE_RECORD=https://clowder.edap-cluster.com/files/67c61fd3e4b096bca877eff6; RECORD_SOURCE_LEVEL=Extraction document; SOURCE_URL=https://echa.europa.eu/; SUBSOURCE_URL=https://echa.europa.eu/registration-dossier/-/registered-dossier/24855/7/6/3?documentUUID=07ed0690-2bf9-419e-8ccc-30c37dab3fe1; YEAR=1977; ORIGINAL_YEAR=1977; STUDY_GROUP=ECHA IUCLID:15827097: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_592f1e6aa088d65cd7c4a8a8d2298d72
ToxValDB_ECHA_IUCLID LEL ~731 ppm Sheep oral short-term; 14 days short-term QUALITY=2 (reliable with restrictions); STORED_SOURCE_RECORD=https://clowder.edap-cluster.com/files/66a7cb96e4b0a7c65d226a94; RECORD_SOURCE_LEVEL=Extraction document; SOURCE_URL=https://echa.europa.eu/; SUBSOURCE_URL=https://echa.europa.eu/registration-dossier/-/registered-dossier/24962/7/6/2?documentUUID=dfc1dee8-bb78-4fd3-b706-372ddde549af; YEAR=1996; ORIGINAL_YEAR=1996; STUDY_GROUP=ECHA IUCLID_dup_Repeated Dose Toxicity Oral_15830373_15832877_15836688_15840371_15842751_15843448_15845544:-:--; 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_1af5230e229d1c877d2660e0a369d87a
ToxValDB_ECHA_IUCLID LOAEL =125 mg/kg bw/day Rat oral subchronic; 90 days subchronic QUALITY=2 (reliable with restrictions); STORED_SOURCE_RECORD=https://clowder.edap-cluster.com/files/669eadc7e4b0a7c65d1c5fc5; RECORD_SOURCE_LEVEL=Extraction document; SOURCE_URL=https://echa.europa.eu/; SUBSOURCE_URL=https://echa.europa.eu/registration-dossier/-/registered-dossier/10329/7/6/2?documentUUID=9335e422-4b04-439e-b32c-4a913c2da116; YEAR=2013; ORIGINAL_YEAR=2013; TOXICOLOGICAL_EFFECT=histopathology: nonneoplastic; TOXICOLOGICAL_EFFECT_CATEGORY=nonneoplastic histopathology; STUDY_GROUP=ECHA IUCLID_dup_Repeated Dose Toxicity Oral_15847227_15847468_15848640_15848676_15848947_15848951_15850702_15850703_15850704_15850705_15850706_15850707_15850708_15850709_15850710_15850711_15850712_15850713: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_00676d649c76c64849dab92425be8636
ToxValDB_ECHA_IUCLID NOAEC =7.5 mg/m3 Rat inhalation - developmental QUALITY=1 (reliable without restriction); STORED_SOURCE_RECORD=https://clowder.edap-cluster.com/files/66a7d215e4b0a7c65d2316a1; RECORD_SOURCE_LEVEL=Extraction document; SOURCE_URL=https://echa.europa.eu/; SUBSOURCE_URL=https://echa.europa.eu/registration-dossier/-/registered-dossier/1803/7/9/3?documentUUID=93089a17-9c2c-4eaf-8903-70c9beb87b12; YEAR=2018; ORIGINAL_YEAR=2018; TOXICOLOGICAL_EFFECT=fetus: changes in sex ratio|fetus: fetal/pup body weight changes|fetus: changes in litter size and weights|fetus: external malformations|fetus: skeletal malformations|fetus: visceral malformations; TOXICOLOGICAL_EFFECT_CATEGORY=development; STUDY_GROUP=ECHA IUCLID_dup_Developmental Toxicity Teratogenicity_15820793_15821376_15821531_15821592_15821667:M/F:-fetal; 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_128fb7ffc5b43921d687956bec6ca77a
ToxValDB_ECHA_IUCLID NOAEC =1.96 mg/m3 Rat inhalation short-term; 10 days short-term QUALITY=1 (reliable without restriction); STORED_SOURCE_RECORD=https://clowder.edap-cluster.com/files/67c61fa0e4b096bca877e312; RECORD_SOURCE_LEVEL=Extraction document; SOURCE_URL=https://echa.europa.eu/; SUBSOURCE_URL=https://echa.europa.eu/registration-dossier/-/registered-dossier/13376/7/6/3?documentUUID=1bb64f22-9e4c-4f54-991f-a093ab5588fc; YEAR=2008; ORIGINAL_YEAR=2008; STUDY_GROUP=ECHA IUCLID:15826939: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_b860d08df8e8c7b27c1804413734155f
ToxValDB_ECHA_IUCLID NOAEL =200 mg/kg bw/day Rat oral - developmental QUALITY=2 (reliable with restrictions); STORED_SOURCE_RECORD=https://clowder.edap-cluster.com/files/669eac6ee4b0a7c65d1bf122; RECORD_SOURCE_LEVEL=Extraction document; SOURCE_URL=https://echa.europa.eu/; SUBSOURCE_URL=https://echa.europa.eu/registration-dossier/-/registered-dossier/14696/7/9/3?documentUUID=e1d3e977-4ed0-49fc-861b-0d67daaf4fde; YEAR=1995; ORIGINAL_YEAR=1995; STUDY_GROUP=ECHA IUCLID_dup_Developmental Toxicity Teratogenicity_15820650_15820651_15820673_15820985_15820993_15821730_15824230_15824231_15824232_15824233_15824234_15824235:M/F:-fetal; 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_70077948745acaa946b78013c60e2d4a
ToxValDB_ECHA_IUCLID NOAEL =400 mg/kg bw/day Rat oral - developmental QUALITY=2 (reliable with restrictions); STORED_SOURCE_RECORD=https://clowder.edap-cluster.com/files/669eabe9e4b0a7c65d1bc68a; RECORD_SOURCE_LEVEL=Extraction document; SOURCE_URL=https://echa.europa.eu/; SUBSOURCE_URL=https://echa.europa.eu/registration-dossier/-/registered-dossier/13376/7/9/3?documentUUID=1bb64f22-9e4c-4f54-991f-a093ab5588fc; YEAR=2008; ORIGINAL_YEAR=2008; STUDY_GROUP=ECHA IUCLID_dup_Developmental Toxicity Teratogenicity_15820650_15820651_15820673_15820985_15820993_15821730_15824230_15824231_15824232_15824233_15824234_15824235:M/F:-fetal; QC_CATEGORY=Programmatically extracted from structured data source; Source overall passed QC, and this record was expert reviewed; QC_STATUS=pass; SOURCE_HASH=ToxValhc_000740ca595654ca7a18084b25335caa
ToxValDB_ECHA_IUCLID NOAEL ~240 mg/kg bw/day Sheep oral short-term; 28 days short-term QUALITY=2 (reliable with restrictions); STORED_SOURCE_RECORD=https://clowder.edap-cluster.com/files/66a7cc1ae4b0a7c65d228eec; RECORD_SOURCE_LEVEL=Extraction document; SOURCE_URL=https://echa.europa.eu/; SUBSOURCE_URL=https://echa.europa.eu/registration-dossier/-/registered-dossier/11214/7/6/2?documentUUID=fcaa6bea-650a-413b-94a6-3d002945fc60; YEAR=1982; ORIGINAL_YEAR=1982; STUDY_GROUP=ECHA IUCLID_dup_Repeated Dose Toxicity Oral_15831592_15833010_15836300_15838074_15839691_15841330_15845352: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_336b101d3d234b9fe42a8f72b142f3c3
ToxValDB_ECHA_IUCLID NOAEL =31.25 mg/kg bw/day Rat oral subchronic; 90 days subchronic QUALITY=2 (reliable with restrictions); STORED_SOURCE_RECORD=https://clowder.edap-cluster.com/files/66a7cbd8e4b0a7c65d227c5d; RECORD_SOURCE_LEVEL=Extraction document; SOURCE_URL=https://echa.europa.eu/; SUBSOURCE_URL=https://echa.europa.eu/registration-dossier/-/registered-dossier/25400/7/6/2?documentUUID=a83e3d7f-2fc0-4f85-bebd-551b8cb28c3f; YEAR=2020; ORIGINAL_YEAR=2020; TOXICOLOGICAL_EFFECT=haematology|histopathology: non-neoplastic|organ weights and organ / body weight ratios; TOXICOLOGICAL_EFFECT_CATEGORY=hematology|nonneoplastic histopathology|organ weight; STUDY_GROUP=ECHA IUCLID_dup_Repeated Dose Toxicity Oral_15847227_15847468_15848640_15848676_15848947_15848951_15850702_15850703_15850704_15850705_15850706_15850707_15850708_15850709_15850710_15850711_15850712_15850713: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_88dff0c829a2181d0ba79bfeaabe8612
ToxValDB_ECOTOX 15 endpoints
Source Endpoint Type Value Unit Species Route Duration Study Type Reference
ToxValDB_ECOTOX LOEL =0.4 % Rat oral short-term; 20 days reproduction developmental LONG_REF=J. Nutr.95:287-294 Schlicker,S.A., and D.H. Cox Maternal Dietary Zinc, and Development and Zinc, Iron, and Copper Content of the Rat Fetus 1968; TITLE=Maternal Dietary Zinc, and Development and Zinc, Iron, and Copper Content of the Rat Fetus; AUTHOR=Schlicker,S.A., and D.H. Cox; DOI=10.1093/jn/95.2.287; QUALITY=Control type: Concurrent control; EXTERNAL_SOURCE_ID=68036; EXTERNAL_SOURCE_ID_DESC=ECOTOX Reference Number; STORED_SOURCE_RECORD=https://clowder.edap-cluster.com/files/6759bce8e4b0a7c65d37bc5f; RECORD_SOURCE_LEVEL=Extraction document; SOURCE_URL=https://cfpub.epa.gov/ecotox/; YEAR=1968; ORIGINAL_YEAR=1968; TOXICOLOGICAL_EFFECT=Accumulation: Residue|Biochemistry: Copper (Cu) content|Growth: Weight|Morphology: Weight; TOXICOLOGICAL_EFFECT_CATEGORY=body weight|other; STUDY_GROUP=ECOTOX_dup_EPA ORD_15594320_15597202:F:--; QC_CATEGORY=Data source QC'd by data provider prior to ECOTOX import; QC_STATUS=not determined; SOURCE_HASH=7e8a1f7aef69ecae9e6ec42af42e1af0
ToxValDB_ECOTOX LOEL =31.2 mg/kg bw/day Rat oral chronic; 120 days chronic LONG_REF=Int. J. Vitam. Nutr. Res.56:329-337 Shankar,S., P.R. Sundaresan, and S. Mohla Effect of Chronic Administration of Excess Dietary Vitamin A and Zinc on Lipid Metabolism in Rats 1986; TITLE=Effect of Chronic Administration of Excess Dietary Vitamin A and Zinc on Lipid Metabolism in Rats; AUTHOR=Shankar,S., P.R. Sundaresan, and S. Mohla; QUALITY=Control type: Concurrent control; EXTERNAL_SOURCE_ID=79334; EXTERNAL_SOURCE_ID_DESC=ECOTOX Reference Number; STORED_SOURCE_RECORD=https://clowder.edap-cluster.com/files/6759bce8e4b0a7c65d37bc5f; RECORD_SOURCE_LEVEL=Extraction document; SOURCE_URL=https://cfpub.epa.gov/ecotox/; YEAR=1986; ORIGINAL_YEAR=1986; TOXICOLOGICAL_EFFECT=Accumulation: Residue|Biochemistry: Cholesterol|Biochemistry: Total lipids|Biochemistry: Vitamin A; TOXICOLOGICAL_EFFECT_CATEGORY=clinical chemistry|other; STUDY_GROUP=ECOTOX_dup_EPA ORD_15595646_15596056:F:--; QC_CATEGORY=Data source QC'd by data provider prior to ECOTOX import; QC_STATUS=not determined; SOURCE_HASH=6bfe6812185848bb5fd44df8c4e3238f
ToxValDB_ECOTOX LOEL =1000 ppm Rat oral short-term; 10 days short-term LONG_REF=J. Nutr. Biochem.15(4): 206-209 Szabo,J., M. Hegedus, G. Bruckner, E. Kosa, E. Andrasofszky, and E. Berta Large Doses of Zinc Oxide Increases the Activity of Hydrolases in Rats 2004; TITLE=Large Doses of Zinc Oxide Increases the Activity of Hydrolases in Rats; AUTHOR=Szabo,J., M. Hegedus, G. Bruckner, E. Kosa, E. Andrasofszky, and E. Berta; DOI=10.1016/j.jnutbio.2003.09.005; QUALITY=Control type: Concurrent control; EXTERNAL_SOURCE_ID=100797; EXTERNAL_SOURCE_ID_DESC=ECOTOX Reference Number; STORED_SOURCE_RECORD=https://clowder.edap-cluster.com/files/6759bce8e4b0a7c65d37bc5f; RECORD_SOURCE_LEVEL=Extraction document; SOURCE_URL=https://cfpub.epa.gov/ecotox/; YEAR=2004; ORIGINAL_YEAR=2004; TOXICOLOGICAL_EFFECT=Enzyme(s): Amylase|Enzyme(s): Lipase|Enzyme(s): Protease|Enzyme(s): Trypsin; TOXICOLOGICAL_EFFECT_CATEGORY=clinical chemistry|enzyme activity; STUDY_GROUP=ECOTOX:15595835:M:--; QC_CATEGORY=Data source QC'd by data provider prior to ECOTOX import; QC_STATUS=not determined; SOURCE_HASH=3bf0813b6a9b87a9152c2545dfb01d7d
ToxValDB_ECOTOX LOEL =1200 ppm Rat oral short-term; 21 days short-term LONG_REF=Proc. Soc. Exp. Biol. Med.152:192-194 Ansari,M.S., W.J. Miller, M.W. Neathery, J.W. Lassiter, R.P. Gentry, and R.L. Kincaid Zinc Metabolism and Homeostasis in Rats Fed a Wide Range of High Dietary Zinc Levels 1976; TITLE=Zinc Metabolism and Homeostasis in Rats Fed a Wide Range of High Dietary Zinc Levels; AUTHOR=Ansari,M.S., W.J. Miller, M.W. Neathery, J.W. Lassiter, R.P. Gentry, and R.L. Kincaid; DOI=10.3181/00379727-152-39358; QUALITY=Control type: Concurrent control; EXTERNAL_SOURCE_ID=68021; EXTERNAL_SOURCE_ID_DESC=ECOTOX Reference Number; STORED_SOURCE_RECORD=https://clowder.edap-cluster.com/files/6759bce8e4b0a7c65d37bc5f; RECORD_SOURCE_LEVEL=Extraction document; SOURCE_URL=https://cfpub.epa.gov/ecotox/; YEAR=1976; ORIGINAL_YEAR=1976; TOXICOLOGICAL_EFFECT=Accumulation: Residue; TOXICOLOGICAL_EFFECT_CATEGORY=other; STUDY_GROUP=ECOTOX_dup_EPA ORD_15596631_15601911_15603183_15603184_15610362_15610363:M:--; QC_CATEGORY=Data source QC'd by data provider prior to ECOTOX import; QC_STATUS=not determined; SOURCE_HASH=f348fe139df36d6e82744086bb1c8a09
ToxValDB_ECOTOX LOEL =6010 ppm Mouse oral short-term; 10 days short-term LONG_REF=Am. J. Vet. Res.56(3): 334-339 Zhang,P., G.E. Duhamel, J.V. Mysore, M.P. Carlson, and N.R. Schneider Prophylactic Effect of Dietary Zinc in a Laboratory Mouse Model of Swine Dysentery 1995; TITLE=Prophylactic Effect of Dietary Zinc in a Laboratory Mouse Model of Swine Dysentery; AUTHOR=Zhang,P., G.E. Duhamel, J.V. Mysore, M.P. Carlson, and N.R. Schneider; QUALITY=Control type: Concurrent control; EXTERNAL_SOURCE_ID=86644; EXTERNAL_SOURCE_ID_DESC=ECOTOX Reference Number; STORED_SOURCE_RECORD=https://clowder.edap-cluster.com/files/6759bce8e4b0a7c65d37bc5f; RECORD_SOURCE_LEVEL=Extraction document; SOURCE_URL=https://cfpub.epa.gov/ecotox/; YEAR=1995; ORIGINAL_YEAR=1995; TOXICOLOGICAL_EFFECT=Accumulation: Residue; TOXICOLOGICAL_EFFECT_CATEGORY=other; STUDY_GROUP=ECOTOX:15597911:F:--; QC_CATEGORY=Data source QC'd by data provider prior to ECOTOX import; QC_STATUS=not determined; SOURCE_HASH=3d7064d679e5547a417477d10b588e85
ToxValDB_ECOTOX LOEL =2400 ppm Rat oral short-term; 21 days short-term LONG_REF=Proc. Soc. Exp. Biol. Med.152:192-194 Ansari,M.S., W.J. Miller, M.W. Neathery, J.W. Lassiter, R.P. Gentry, and R.L. Kincaid Zinc Metabolism and Homeostasis in Rats Fed a Wide Range of High Dietary Zinc Levels 1976; TITLE=Zinc Metabolism and Homeostasis in Rats Fed a Wide Range of High Dietary Zinc Levels; AUTHOR=Ansari,M.S., W.J. Miller, M.W. Neathery, J.W. Lassiter, R.P. Gentry, and R.L. Kincaid; DOI=10.3181/00379727-152-39358; QUALITY=Control type: Concurrent control; EXTERNAL_SOURCE_ID=68021; EXTERNAL_SOURCE_ID_DESC=ECOTOX Reference Number; STORED_SOURCE_RECORD=https://clowder.edap-cluster.com/files/6759bce8e4b0a7c65d37bc5f; RECORD_SOURCE_LEVEL=Extraction document; SOURCE_URL=https://cfpub.epa.gov/ecotox/; YEAR=1976; ORIGINAL_YEAR=1976; TOXICOLOGICAL_EFFECT=Accumulation: Residue; TOXICOLOGICAL_EFFECT_CATEGORY=other; STUDY_GROUP=ECOTOX_dup_EPA ORD_15596631_15601911_15603183_15603184_15610362_15610363:M:--; QC_CATEGORY=Data source QC'd by data provider prior to ECOTOX import; QC_STATUS=not determined; SOURCE_HASH=0bdf651349b67c89989a3353b736f777
ToxValDB_ECOTOX LOEL =4.8 mg/kg bw/day Rat oral subchronic; 42 days subchronic LONG_REF=- | Nutr. Res.20(3): 413-425 Subramanian,P., S. Sivabalan, V.P. Menon, and K. Vasudevan Influence of Chronic Zinc Supplementation on Biochemical Variables and Circadian Rhythms in Wistar Rats 2000; TITLE=Influence of Chronic Zinc Supplementation on Biochemical Variables and Circadian Rhythms in Wistar Rats; AUTHOR=Subramanian,P., S. Sivabalan, V.P. Menon, and K. Vasudevan; QUALITY=Control type: Concurrent control; EXTERNAL_SOURCE_ID=68812; EXTERNAL_SOURCE_ID_DESC=ECOTOX Reference Number; STORED_SOURCE_RECORD=https://clowder.edap-cluster.com/files/6759bce8e4b0a7c65d37bc5f; RECORD_SOURCE_LEVEL=Extraction document; SOURCE_URL=https://cfpub.epa.gov/ecotox/; YEAR=2000; ORIGINAL_YEAR=2000; TOXICOLOGICAL_EFFECT=Biochemistry: Iron content|Biochemistry: Thiobarbituric acid reactive substances|Enzyme(s): Ceruloplasmin activity; TOXICOLOGICAL_EFFECT_CATEGORY=clinical chemistry|enzyme activity|other; STUDY_GROUP=ECOTOX:15613045:M:--; QC_CATEGORY=Data source QC'd by data provider prior to ECOTOX import; Source overall passed QC, and this record was expert reviewed and revised from ECOTOX source; QC_STATUS=pass; SOURCE_HASH=2b51eee8eaf3867c51cf8a88986f58f1
ToxValDB_ECOTOX NOEL =200 ppm Rat oral short-term; 21 days short-term LONG_REF=Toxicol. Appl. Pharmacol.84:12-24 Agarwal,D.K., S. Eustis, J.C. Lamb IV, C.W. Jameson, and W.M. Kluwe Influence of Dietary Zinc on Di(2-ethylhexyl)Phthalate-Induced Testicular Atrophy and Zinc Depletion in Adult Rats 1986; TITLE=Influence of Dietary Zinc on Di(2-ethylhexyl)Phthalate-Induced Testicular Atrophy and Zinc Depletion in Adult Rats; AUTHOR=Agarwal,D.K., S. Eustis, J.C. Lamb IV, C.W. Jameson, and W.M. Kluwe; DOI=10.1016/0041-008x(86)90412-6; QUALITY=Control type: Carrier or solvent control; EXTERNAL_SOURCE_ID=67779; EXTERNAL_SOURCE_ID_DESC=ECOTOX Reference Number; STORED_SOURCE_RECORD=https://clowder.edap-cluster.com/files/6759bce8e4b0a7c65d37bc5f; RECORD_SOURCE_LEVEL=Extraction document; SOURCE_URL=https://cfpub.epa.gov/ecotox/; YEAR=1986; ORIGINAL_YEAR=1986; TOXICOLOGICAL_EFFECT=Accumulation: Residue|Biochemistry: Cholesterol|Biochemistry: Sulfhydryl|Biochemistry: Triglycerides|Enzyme(s): Lactate dehydrogenase|Growth: Weight|Histology: Atrophy|Morphology: Organ weight in relationship to body weight|Morphology: Weight; TOXICOLOGICAL_EFFECT_CATEGORY=body weight|clinical chemistry|nonneoplastic histopathology|organ weight|other; STUDY_GROUP=ECOTOX:15594126:M:--; QC_CATEGORY=Data source QC'd by data provider prior to ECOTOX import; QC_STATUS=not determined; SOURCE_HASH=6adb079de583dee0dd1b140c8a0a1359
ToxValDB_ECOTOX NOEL =160 mg/kg bw/day Rat multiple short-term; 7 days short-term LONG_REF=Br. J. Nutr.57(1): 35-44 Coppen,D.E., and N.T. Davies Studies on the Effects of Dietary Zinc Dose on 65Zn Absorption In Vivo and on the Effects of Zn Status on 65Zn Absorption and Body Loss in Young Rats 1987; TITLE=Studies on the Effects of Dietary Zinc Dose on 65Zn Absorption In Vivo and on the Effects of Zn Status on 65Zn Absorption and Body Loss in Young Rats; AUTHOR=Coppen,D.E., and N.T. Davies; DOI=10.1079/bjn19870007; QUALITY=Control type: Concurrent control; EXTERNAL_SOURCE_ID=68815; EXTERNAL_SOURCE_ID_DESC=ECOTOX Reference Number; STORED_SOURCE_RECORD=https://clowder.edap-cluster.com/files/6759bce8e4b0a7c65d37bc5f; RECORD_SOURCE_LEVEL=Extraction document; SOURCE_URL=https://cfpub.epa.gov/ecotox/; YEAR=1987; ORIGINAL_YEAR=1987; TOXICOLOGICAL_EFFECT=Growth: Weight; TOXICOLOGICAL_EFFECT_CATEGORY=body weight; STUDY_GROUP=ECOTOX:15594936:M:--; QC_CATEGORY=Data source QC'd by data provider prior to ECOTOX import; QC_STATUS=not determined; SOURCE_HASH=eef87ceb15d5156136369a42c6f74a52
ToxValDB_ECOTOX NOEL =0.5 % Rat oral short-term; 23 days reproduction developmental LONG_REF=J. Nutr.98:303-311 Ketcheson,M.R., G.P. Barron, and D.H. Cox Relationship of Maternal Dietary Zinc During Gestation and Lactation to Development and Zinc, Iron and Copper Content of the Postnatal Rat 1969; TITLE=Relationship of Maternal Dietary Zinc During Gestation and Lactation to Development and Zinc, Iron and Copper Content of the Postnatal Rat; AUTHOR=Ketcheson,M.R., G.P. Barron, and D.H. Cox; DOI=10.1093/jn/98.3.303; QUALITY=Control type: Concurrent control; EXTERNAL_SOURCE_ID=78356; EXTERNAL_SOURCE_ID_DESC=ECOTOX Reference Number; STORED_SOURCE_RECORD=https://clowder.edap-cluster.com/files/6759bce8e4b0a7c65d37bc5f; RECORD_SOURCE_LEVEL=Extraction document; SOURCE_URL=https://cfpub.epa.gov/ecotox/; YEAR=1969; ORIGINAL_YEAR=1969; TOXICOLOGICAL_EFFECT=Biochemistry: Copper (Cu) content|Biochemistry: Iron content|Feeding behavior: Food consumption|Morphology: Weight; TOXICOLOGICAL_EFFECT_CATEGORY=food and/or water consumption|other; STUDY_GROUP=ECOTOX_dup_EPA ORD_15595307_15595308_15595309_15599517:F:--; QC_CATEGORY=Data source QC'd by data provider prior to ECOTOX import; QC_STATUS=not determined; SOURCE_HASH=596aacdcd28c9a2288e4a05b7b0cb9f4
ToxValDB_ECOTOX NOEL =0.2 % Rat oral short-term; 23 days reproduction developmental LONG_REF=J. Nutr.98:303-311 Ketcheson,M.R., G.P. Barron, and D.H. Cox Relationship of Maternal Dietary Zinc During Gestation and Lactation to Development and Zinc, Iron and Copper Content of the Postnatal Rat 1969; TITLE=Relationship of Maternal Dietary Zinc During Gestation and Lactation to Development and Zinc, Iron and Copper Content of the Postnatal Rat; AUTHOR=Ketcheson,M.R., G.P. Barron, and D.H. Cox; DOI=10.1093/jn/98.3.303; QUALITY=Control type: Concurrent control; EXTERNAL_SOURCE_ID=78356; EXTERNAL_SOURCE_ID_DESC=ECOTOX Reference Number; STORED_SOURCE_RECORD=https://clowder.edap-cluster.com/files/6759bce8e4b0a7c65d37bc5f; RECORD_SOURCE_LEVEL=Extraction document; SOURCE_URL=https://cfpub.epa.gov/ecotox/; YEAR=1969; ORIGINAL_YEAR=1969; TOXICOLOGICAL_EFFECT=Biochemistry: Copper (Cu) content|Biochemistry: Iron content|Growth: Weight|Morphology: Weight; TOXICOLOGICAL_EFFECT_CATEGORY=body weight|other; STUDY_GROUP=ECOTOX_dup_EPA ORD_15595307_15595308_15595309_15599517:F:--; QC_CATEGORY=Data source QC'd by data provider prior to ECOTOX import; QC_STATUS=not determined; SOURCE_HASH=820fd639219c01a602809f6447952547
ToxValDB_ECOTOX NOEL =97.46 ppm Rat oral short-term; 17 days developmental LONG_REF=Toxicology126:9-21 Bui,L.M., M.W. Taubeneck, J.F. Commisso, J.Y. Uriu-Hare, W.D. Faber, and C.L. Keen Altered Zinc Metabolism Contributes to the Developmental Toxicity of 2-Ethylhexanoic Acid, 2-Ethylhexanol and Valproic Acid 1998; TITLE=Altered Zinc Metabolism Contributes to the Developmental Toxicity of 2-Ethylhexanoic Acid, 2-Ethylhexanol and Valproic Acid; AUTHOR=Bui,L.M., M.W. Taubeneck, J.F. Commisso, J.Y. Uriu-Hare, W.D. Faber, and C.L. Keen; DOI=10.1016/s0300-483x(97)00171-6; QUALITY=Control type: Carrier or solvent control; EXTERNAL_SOURCE_ID=67778; EXTERNAL_SOURCE_ID_DESC=ECOTOX Reference Number; STORED_SOURCE_RECORD=https://clowder.edap-cluster.com/files/6759bce8e4b0a7c65d37bc5f; RECORD_SOURCE_LEVEL=Extraction document; SOURCE_URL=https://cfpub.epa.gov/ecotox/; YEAR=1998; ORIGINAL_YEAR=1998; TOXICOLOGICAL_EFFECT=Accumulation: Residue|Biochemistry: Metallothionein|Development: Abnormal|Development: Slowed, Retarded, Delayed or Non-development|Development: Weight|Growth: Weight gain|Histology: Hernia|Injury: Hydrocephaly|Morphology: Length|Reproduction: Resorbed embryos; TOXICOLOGICAL_EFFECT_CATEGORY=body weight|development|gross pathology|other|reproduction; STUDY_GROUP=ECOTOX:15597812:F:--; QC_CATEGORY=Data source QC'd by data provider prior to ECOTOX import; QC_STATUS=not determined; SOURCE_HASH=8ccaedbbc98616953ee2fae6f0e079aa
ToxValDB_ECOTOX NOEL =8400 ppm Rat oral short-term; 21 days short-term LONG_REF=Proc. Soc. Exp. Biol. Med.152:192-194 Ansari,M.S., W.J. Miller, M.W. Neathery, J.W. Lassiter, R.P. Gentry, and R.L. Kincaid Zinc Metabolism and Homeostasis in Rats Fed a Wide Range of High Dietary Zinc Levels 1976; TITLE=Zinc Metabolism and Homeostasis in Rats Fed a Wide Range of High Dietary Zinc Levels; AUTHOR=Ansari,M.S., W.J. Miller, M.W. Neathery, J.W. Lassiter, R.P. Gentry, and R.L. Kincaid; DOI=10.3181/00379727-152-39358; QUALITY=Control type: Concurrent control; EXTERNAL_SOURCE_ID=68021; EXTERNAL_SOURCE_ID_DESC=ECOTOX Reference Number; STORED_SOURCE_RECORD=https://clowder.edap-cluster.com/files/6759bce8e4b0a7c65d37bc5f; RECORD_SOURCE_LEVEL=Extraction document; SOURCE_URL=https://cfpub.epa.gov/ecotox/; YEAR=1976; ORIGINAL_YEAR=1976; TOXICOLOGICAL_EFFECT=Accumulation: Residue|Feeding behavior: Food consumption|Growth: Weight gain; TOXICOLOGICAL_EFFECT_CATEGORY=body weight|food and/or water consumption|other; STUDY_GROUP=ECOTOX_dup_EPA ORD_15596631_15601911_15603183_15603184_15610362_15610363:M:--; QC_CATEGORY=Data source QC'd by data provider prior to ECOTOX import; QC_STATUS=not determined; SOURCE_HASH=1a641f8969fcb6476372432011151f6f
ToxValDB_ECOTOX NOEL =20 % w/v Mouse dermal short-term; 5 days short-term LONG_REF=Food Chem. Toxicol.29(1): 57-64 Lansdown,A.B.G. Interspecies Variations in Response to Topical Application of Selected Zinc Compounds 1991; TITLE=Interspecies Variations in Response to Topical Application of Selected Zinc Compounds; AUTHOR=Lansdown,A.B.G.; DOI=10.1016/0278-6915(91)90063-d; QUALITY=Control type: Carrier or solvent control; EXTERNAL_SOURCE_ID=85721; EXTERNAL_SOURCE_ID_DESC=ECOTOX Reference Number; STORED_SOURCE_RECORD=https://clowder.edap-cluster.com/files/6759bce8e4b0a7c65d37bc5f; RECORD_SOURCE_LEVEL=Extraction document; SOURCE_URL=https://cfpub.epa.gov/ecotox/; YEAR=1991; ORIGINAL_YEAR=1991; TOXICOLOGICAL_EFFECT=Genetics: Mitotic index (# mitoses/total cells); TOXICOLOGICAL_EFFECT_CATEGORY=other; STUDY_GROUP=ECOTOX:15609914:M:--; QC_CATEGORY=Data source QC'd by data provider prior to ECOTOX import; QC_STATUS=not determined; SOURCE_HASH=1eaae6dcf15a303ca8c96864ec24098b
ToxValDB_ECOTOX NOEL =7200 ppm Rat oral short-term; 21 days short-term LONG_REF=Proc. Soc. Exp. Biol. Med.152:192-194 Ansari,M.S., W.J. Miller, M.W. Neathery, J.W. Lassiter, R.P. Gentry, and R.L. Kincaid Zinc Metabolism and Homeostasis in Rats Fed a Wide Range of High Dietary Zinc Levels 1976; TITLE=Zinc Metabolism and Homeostasis in Rats Fed a Wide Range of High Dietary Zinc Levels; AUTHOR=Ansari,M.S., W.J. Miller, M.W. Neathery, J.W. Lassiter, R.P. Gentry, and R.L. Kincaid; DOI=10.3181/00379727-152-39358; QUALITY=Control type: Concurrent control; EXTERNAL_SOURCE_ID=68021; EXTERNAL_SOURCE_ID_DESC=ECOTOX Reference Number; STORED_SOURCE_RECORD=https://clowder.edap-cluster.com/files/6759bce8e4b0a7c65d37bc5f; RECORD_SOURCE_LEVEL=Extraction document; SOURCE_URL=https://cfpub.epa.gov/ecotox/; YEAR=1976; ORIGINAL_YEAR=1976; TOXICOLOGICAL_EFFECT=Accumulation: Residue; TOXICOLOGICAL_EFFECT_CATEGORY=other; STUDY_GROUP=ECOTOX_dup_EPA ORD_15596631_15601911_15603183_15603184_15610362_15610363:M:--; QC_CATEGORY=Data source QC'd by data provider prior to ECOTOX import; QC_STATUS=not determined; SOURCE_HASH=c5f39ca3364f03cd73d7afff30a2f997
ToxValDB_GESTIS_DNEL 2 endpoints
Source Endpoint Type Value Unit Species Route Duration Study Type Reference
ToxValDB_GESTIS_DNEL DNEL local =0.5 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_dup_-_15635797_15635798:-:--; 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_0afe08211dcb59355f05b2290e8737f9
ToxValDB_GESTIS_DNEL DNEL systemic =5 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_dup_-_15635797_15635798:-:--; 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_828b69a487421f7fe32e65e2f03a0056
ToxValDB_NIOSH_IDLH 2 endpoints
Source Endpoint Type Value Unit Species Route Duration Study Type Reference
ToxValDB_NIOSH_IDLH LEL =320 mg/m3 Human inhalation acute; 3 hours occupational LONG_REF=Hammond JW [1944]. Metal fume fever in the crushed stone industry. J Ind Hyg Toxicol 26(4):117-119.; STORED_SOURCE_RECORD=https://clowder.edap-cluster.com/files/68c9b384e4b02565fc7d7211; RECORD_SOURCE_LEVEL=Extraction document; SOURCE_URL=https://www.cdc.gov/niosh/idlh/; SUBSOURCE_URL=https://www.cdc.gov/niosh/idlh/1314132.html; YEAR=1994; ORIGINAL_YEAR=1994; TOXICOLOGICAL_EFFECT=nausea on the job, and chills, shortness of breath, and severe chest pains 2 to 12 hours later; STUDY_GROUP=NIOSH IDLH:15953833:-:--; QC_CATEGORY=Manually extracted from unstructured data source; Source overall passed QC, and this record was manually checked; QC_STATUS=pass; SOURCE_HASH=ToxValhc_ceb47f03f2e0fa564077f3be3b8daa9a
ToxValDB_NIOSH_IDLH LEL =600 mg/m3 Human inhalation acute; 12 minutes clinical LONG_REF=Sturgis CC, Thompson PD [1927]. Metal fume fever: I. Clinical observations on the effect of the experimental inhalation of zinc oxide by two apparently normal persons. J Ind Hyg 9(3):88-97.; STORED_SOURCE_RECORD=https://clowder.edap-cluster.com/files/68c9b384e4b02565fc7d7211; RECORD_SOURCE_LEVEL=Extraction document; SOURCE_URL=https://www.cdc.gov/niosh/idlh/; SUBSOURCE_URL=https://www.cdc.gov/niosh/idlh/1314132.html; YEAR=1994; ORIGINAL_YEAR=1994; TOXICOLOGICAL_EFFECT=headaches, chills, and fever with cough and a decrease in vital capacity which persisted for 15 hours after exposure; STUDY_GROUP=NIOSH IDLH:15953834:-:--; QC_CATEGORY=Manually extracted from unstructured data source; Source overall passed QC, and this record was manually checked; QC_STATUS=pass; SOURCE_HASH=ToxValhc_1e81bfe7ebdea3f6cc59db87bd89c690
UnifiedCodex:SCCNFP:beta.noael_studies 6 endpoints
Source Endpoint Type Value Unit Species Route Duration Study Type Reference
UnifiedCodex:SCCNFP:beta.noael_studies - 3000 ppm rat - - - SOURCE_SUBDIR=out222_en; REPORT_TITLE=OPINION CONCERNING ZINC OXIDE COLIPA n° S 76; OPINION_NUMBER=SCCNFP/0649/03; COMMITTEE=SCCNFP; REPORT_DATE=25 June 2003; VALUE_TEXT=3000; DOSE=e and cholesterol were reduced and alkaline phosphatase and urea nitrogen were increased in high dose animals.; EFFECT=e and cholesterol were reduced and alkaline phosphatase and urea nitrogen were increased in high dose animals. High dose females showed reduced ALAT and increased calcium levels, ASAT was increased in high dose males. Absolute and relative thyroid weights of males and kidney weights of females were increased at the highest dose. Gross pathology and histopathology showed changes in kidneys, thyroids, pancreas (degeneration/necrosis of acinar cells, clarification of nucleoli), gastrointestinal tract, and spleen. The NOEL for mice in this study was found at the mid dose at 3000 ppm (about 470 mg ZnSO4.7 H2O/kg bw (104 mg Zn2+/kg bw). Wistar rats : at the high dose level a moderate reduction in leucocyte counts, slightly decreased hematocrit and haemoglobin values (males only) and decreased total protein and cholesterol values were recorded. Absolute and relative liver weights and relative kidney weights were decreased in high dose males. Histopathology showed pancreatic damage (degeneration, necrosis of acinar cells, clarification; CITATION_NUMBERS=[]; DETAILS_JSON={"cas_number":"1314-13-2","citation":"","dose":"e and cholesterol were reduced and alkaline phosphatase and urea nitrogen were increased in high dose animals.","duration":"","effect":"e and cholesterol were reduced and alkaline phosphatase and urea nitrogen were increased in high dose animals. High dose females showed reduced ALAT and increased calcium levels, ASAT was increased in high dose males. Absolute and relative thyroid weights of males and kidney weights of females were increased at the highest dose. Gross pathology and histopathology showed changes in kidneys, thyroids, pancreas (degeneration/necrosis of acinar cells, clarification of nucleoli), gastrointestinal tract, and spleen. The NOEL for mice in this study was found at the mid dose at 3000 ppm (about 470 mg ZnSO4.7 H2O/kg bw (104 mg Zn2+/kg bw). Wistar rats : at the high dose level a moderate reduction in leucocyte counts, slightly decreased hematocrit and haemoglobin values (males only) and decreased total protein and cholesterol values were recorded. Absolute and relative liver weights and relative kidney weights were decreased in high dose males. Histopathology showed pancreatic damage (degeneration, necrosis of acinar cells, clarification","endpoint":"","ingredient":"codes","loael_value":"","noael_unit":"ppm","noael_value":"3000","page":7,"route":"","species":"rat","study_id":"out222_en_noael_001"}
UnifiedCodex:SCCNFP:beta.noael_studies - 3000 ppm rat oral - - SOURCE_SUBDIR=out222_en; REPORT_TITLE=OPINION CONCERNING ZINC OXIDE COLIPA n° S 76; OPINION_NUMBER=SCCNFP/0649/03; COMMITTEE=SCCNFP; REPORT_DATE=25 June 2003; VALUE_TEXT=3000; DOSE=Wistar rats : at the high dose level a moderate reduction in leucocyte counts, slightly decreased hematocrit and haemoglobin values (males only) and decreased total protein and cholesterol values were recorded.; EFFECT=ZnSO4.7 H2O/kg bw (104 mg Zn2+/kg bw). Wistar rats : at the high dose level a moderate reduction in leucocyte counts, slightly decreased hematocrit and haemoglobin values (males only) and decreased total protein and cholesterol values were recorded. Absolute and relative liver weights and relative kidney weights were decreased in high dose males. Histopathology showed pancreatic damage (degeneration, necrosis of acinar cells, clarification of centroacinar cells and interstitial fibrosis) in high dose animals. The NOEL for rats was found at the mid dose at 3000 ppm (about 240 mg ZnSO4.7 H2O/kg bw for males and females, respectively (53.5 mg Zn2+/kg bw). Ref. : 14 Human studies Since zinc is an essential trace element for all mammalian species, its presence in the diet of humans and animals as well as in drinking water is required. In this regard, the mammalian organism is used to handle varying quantities of externally administered zinc, such that Zn2+ homeostasis is regulated via control mechanisms of absorption and excretion.; CITATION=Ref. : 14 Human studies Since zinc is an essential trace element for all mammalian species, its presence in the diet of humans and animals as well as in drinking water is required; CITATION_NUMBERS=[14]; REFERENCE=Ref. : 14 Human studies Since zinc is an essential trace element for all mammalian species, its presence in the diet of humans and animals as well as in drinking water is required; DETAILS_JSON={"cas_number":"1314-13-2","citation":"Ref. : 14 Human studies Since zinc is an essential trace element for all mammalian species, its presence in the diet of humans and animals as well as in drinking water is required","dose":"Wistar rats : at the high dose level a moderate reduction in leucocyte counts, slightly decreased hematocrit and haemoglobin values (males only) and decreased total protein and cholesterol values were recorded.","duration":"","effect":"ZnSO4.7 H2O/kg bw (104 mg Zn2+/kg bw). Wistar rats : at the high dose level a moderate reduction in leucocyte counts, slightly decreased hematocrit and haemoglobin values (males only) and decreased total protein and cholesterol values were recorded. Absolute and relative liver weights and relative kidney weights were decreased in high dose males. Histopathology showed pancreatic damage (degeneration, necrosis of acinar cells, clarification of centroacinar cells and interstitial fibrosis) in high dose animals. The NOEL for rats was found at the mid dose at 3000 ppm (about 240 mg ZnSO4.7 H2O/kg bw for males and females, respectively (53.5 mg Zn2+/kg bw). Ref. : 14 Human studies Since zinc is an essential trace element for all mammalian species, its presence in the diet of humans and animals as well as in drinking water is required. In this regard, the mammalian organism is used to handle varying quantities of externally administered zinc, such that Zn2+ homeostasis is regulated via control mechanisms of absorption and excretion.","endpoint":"","ingredient":"codes","loael_value":"","noael_unit":"ppm","noael_value":"3000","page":7,"route":"oral","species":"rat","study_id":"out222_en_noael_002"}
UnifiedCodex:SCCNFP:beta.noael_studies - 0.5 mg/kg/day human oral 6 weeks - SOURCE_SUBDIR=out222_en; REPORT_TITLE=OPINION CONCERNING ZINC OXIDE COLIPA n° S 76; OPINION_NUMBER=SCCNFP/0649/03; COMMITTEE=SCCNFP; REPORT_DATE=25 June 2003; VALUE_TEXT=0.5; DOSE=In this regard, the mammalian organism is used to handle varying quantities of externally administered zinc, such that Zn2+ homeostasis is regulated via control mechanisms of absorption and excretion.; EFFECT=2+/kg bw). Ref. : 14 Human studies Since zinc is an essential trace element for all mammalian species, its presence in the diet of humans and animals as well as in drinking water is required. In this regard, the mammalian organism is used to handle varying quantities of externally administered zinc, such that Zn2+ homeostasis is regulated via control mechanisms of absorption and excretion. In humans, the average daily intake is estimated at about 15 mg of Zn2+. The available evidence from human studies points to a NOEL of about 0.5 mg/kg/day and thus confirms the safe exposure level, which could be predicted from the animal data. A series of human experimental studies have been published which report adverse effects from oral administration of zinc salts : * 47 healthy volunteers ingested ZnSO4 tablets three times a day for 6 weeks, resulting in a total daily dose of 2 mg Zn2+/kg bw. Headaches, nausea, vomiting, loss of appetite and abdominal cramps were seen in 26 of the volunteers. Ref. : 15 * Oral doses of 160 mg ZnSO4/day (2; CITATION=Ref. : 14 Human studies Since zinc is an essential trace element for all mammalian species, its presence in the diet of humans and animals as well as in drinking water is required; CITATION_NUMBERS=[14]; REFERENCE=Ref. : 14 Human studies Since zinc is an essential trace element for all mammalian species, its presence in the diet of humans and animals as well as in drinking water is required; DETAILS_JSON={"cas_number":"1314-13-2","citation":"Ref. : 14 Human studies Since zinc is an essential trace element for all mammalian species, its presence in the diet of humans and animals as well as in drinking water is required","dose":"In this regard, the mammalian organism is used to handle varying quantities of externally administered zinc, such that Zn2+ homeostasis is regulated via control mechanisms of absorption and excretion.","duration":"6 weeks","effect":"2+/kg bw). Ref. : 14 Human studies Since zinc is an essential trace element for all mammalian species, its presence in the diet of humans and animals as well as in drinking water is required. In this regard, the mammalian organism is used to handle varying quantities of externally administered zinc, such that Zn2+ homeostasis is regulated via control mechanisms of absorption and excretion. In humans, the average daily intake is estimated at about 15 mg of Zn2+. The available evidence from human studies points to a NOEL of about 0.5 mg/kg/day and thus confirms the safe exposure level, which could be predicted from the animal data. A series of human experimental studies have been published which report adverse effects from oral administration of zinc salts : * 47 healthy volunteers ingested ZnSO4 tablets three times a day for 6 weeks, resulting in a total daily dose of 2 mg Zn2+/kg bw. Headaches, nausea, vomiting, loss of appetite and abdominal cramps were seen in 26 of the volunteers. Ref. : 15 * Oral doses of 160 mg ZnSO4/day (2","endpoint":"","ingredient":"codes","loael_value":"","noael_unit":"mg/kg/day","noael_value":"0.5","page":7,"route":"oral","species":"human","study_id":"out222_en_noael_003"}
UnifiedCodex:SCCNFP:beta.noael_studies developmental toxicity 42.5 mg/kg rabbit oral developmental developmental toxicity SOURCE_SUBDIR=out222_en; REPORT_TITLE=OPINION CONCERNING ZINC OXIDE COLIPA n° S 76; OPINION_NUMBER=SCCNFP/0649/03; COMMITTEE=SCCNFP; REPORT_DATE=25 June 2003; VALUE_TEXT=42.5; DOSE=Results No compound-related effects were observed at any dose level.; EFFECT=a lutea, implantations, viable foetuses and resorptions. All foetuses were weighed, sexed and examined for gross external defects. In addition, skeletal examinations (in two-thirds of the foetuses) and soft tissue examinations (in the remaining one-third of foetuses) were performed. Results No compound-related effects were observed at any dose level. In particular, there was no indication of any specific teratogenic activity of ZnSO4 under the conditions of this experiment. Conclusion The No Observed Effect Level (NOEL) with regard to maternal and developmental toxicity of ZnSO4 was 42.5 mg/kg (corresponding to about 17 mg/kg if expressed as zinc). Ref. : 27 Species : Female Dutch rabbits Number of animals : 14-19 animals per group Test substance : ZnSO4 (unspecified) 6-amino-nicotinamide (positive control) Doses : ZnSO4 : 0, 0.6, 2.8, 13.0 and 60.0 mg/kg by gavage in water 6-amino-nicotinamide : 2.5 mg/kg by gavage Exposure period : ZnSO4: day 6-18 of gestation (p.c.) 6-amino-nicotinamide: single application at day 19 of gestat; CITATION=Ref. : 27 Species : Female Dutch rabbits Number of animals : 14-19 animals per group Test substance : ZnSO4 (unspecified) 6-amino-nicotinamide (positive control) Doses : ZnSO4 : 0, 0; CITATION_NUMBERS=[27,14,19,4,6]; REFERENCE=Ref. : 27 Species : Female Dutch rabbits Number of animals : 14-19 animals per group Test substance : ZnSO4 (unspecified) 6-amino-nicotinamide (positive control) Doses : ZnSO4 : 0, 0; DETAILS_JSON={"cas_number":"1314-13-2","citation":"Ref. : 27 Species : Female Dutch rabbits Number of animals : 14-19 animals per group Test substance : ZnSO4 (unspecified) 6-amino-nicotinamide (positive control) Doses : ZnSO4 : 0, 0","dose":"Results No compound-related effects were observed at any dose level.","duration":"developmental","effect":"a lutea, implantations, viable foetuses and resorptions. All foetuses were weighed, sexed and examined for gross external defects. In addition, skeletal examinations (in two-thirds of the foetuses) and soft tissue examinations (in the remaining one-third of foetuses) were performed. Results No compound-related effects were observed at any dose level. In particular, there was no indication of any specific teratogenic activity of ZnSO4 under the conditions of this experiment. Conclusion The No Observed Effect Level (NOEL) with regard to maternal and developmental toxicity of ZnSO4 was 42.5 mg/kg (corresponding to about 17 mg/kg if expressed as zinc). Ref. : 27 Species : Female Dutch rabbits Number of animals : 14-19 animals per group Test substance : ZnSO4 (unspecified) 6-amino-nicotinamide (positive control) Doses : ZnSO4 : 0, 0.6, 2.8, 13.0 and 60.0 mg/kg by gavage in water 6-amino-nicotinamide : 2.5 mg/kg by gavage Exposure period : ZnSO4: day 6-18 of gestation (p.c.) 6-amino-nicotinamide: single application at day 19 of gestat","endpoint":"developmental toxicity","ingredient":"codes","loael_value":"","noael_unit":"mg/kg","noael_value":"42.5","page":13,"route":"oral","species":"rabbit","study_id":"out222_en_noael_004"}
UnifiedCodex:SCCNFP:beta.noael_studies developmental toxicity 60 mg/kg rat oral developmental developmental toxicity SOURCE_SUBDIR=out222_en; REPORT_TITLE=OPINION CONCERNING ZINC OXIDE COLIPA n° S 76; OPINION_NUMBER=SCCNFP/0649/03; COMMITTEE=SCCNFP; REPORT_DATE=25 June 2003; VALUE_TEXT=60.0; DOSE=Zinc oxide ____________________________________________________________________________________________ 14 Conclusion The No Observed Effect Level (NOEL) with regard to maternal and developmental toxicity of Zinc Sulfate was at least 60.0 mg/kg (corresponding to about 24 mg/kg if expressed as zinc).; EFFECT=SCCNFP/0649/03, final Evaluation and opinion on : Zinc oxide ____________________________________________________________________________________________ 14 Conclusion The No Observed Effect Level (NOEL) with regard to maternal and developmental toxicity of Zinc Sulfate was at least 60.0 mg/kg (corresponding to about 24 mg/kg if expressed as zinc). Ref. : 28 Species : Female Sprague Dawley: CFE rats Number of animals : 10 animals per group Test substance : ZnO Doses and exposure period 7 groups received the test substance at levels of 2000 (about 100 mg/kg/d) or 4000 ppm (about 200 mg/kg/day) in the diet. 7 equally sized control groups received the basal diet without test substance. 4 groups were fed the test die; CITATION=Ref. : 28 Species : Female Sprague Dawley: CFE rats Number of animals : 10 animals per group Test substance : ZnO Doses and exposure period 7 groups received the test substance at levels; CITATION_NUMBERS=[28,10,7]; REFERENCE=Ref. : 28 Species : Female Sprague Dawley: CFE rats Number of animals : 10 animals per group Test substance : ZnO Doses and exposure period 7 groups received the test substance at levels; DETAILS_JSON={"cas_number":"1314-13-2","citation":"Ref. : 28 Species : Female Sprague Dawley: CFE rats Number of animals : 10 animals per group Test substance : ZnO Doses and exposure period 7 groups received the test substance at levels","dose":"Zinc oxide ____________________________________________________________________________________________ 14 Conclusion The No Observed Effect Level (NOEL) with regard to maternal and developmental toxicity of Zinc Sulfate was at least 60.0 mg/kg (corresponding to about 24 mg/kg if expressed as zinc).","duration":"developmental","effect":"SCCNFP/0649/03, final Evaluation and opinion on : Zinc oxide ____________________________________________________________________________________________ 14 Conclusion The No Observed Effect Level (NOEL) with regard to maternal and developmental toxicity of Zinc Sulfate was at least 60.0 mg/kg (corresponding to about 24 mg/kg if expressed as zinc). Ref. : 28 Species : Female Sprague Dawley: CFE rats Number of animals : 10 animals per group Test substance : ZnO Doses and exposure period 7 groups received the test substance at levels of 2000 (about 100 mg/kg/d) or 4000 ppm (about 200 mg/kg/day) in the diet. 7 equally sized control groups received the basal diet without test substance. 4 groups were fed the test die","endpoint":"developmental toxicity","ingredient":"codes","loael_value":"","noael_unit":"mg/kg","noael_value":"60.0","page":14,"route":"oral","species":"rat","study_id":"out222_en_noael_005"}
UnifiedCodex:SCCNFP:beta.noael_studies developmental toxicity 40 % human oral developmental developmental toxicity SOURCE_SUBDIR=out222_en; REPORT_TITLE=OPINION CONCERNING ZINC OXIDE COLIPA n° S 76; OPINION_NUMBER=SCCNFP/0649/03; COMMITTEE=SCCNFP; REPORT_DATE=25 June 2003; VALUE_TEXT=40; DOSE=Conclusion ZnO, 2000 ppm, administered from day 21 prior to mating until day 15 of gestation induced no adverse effects on foetal development.; EFFECT=e observed in foetal whole body samples. These analytical results support the interpretation that the observed developmental effects of exaggerated high zinc doses are mediated by depletion of certain essential minerals such as copper. Conclusion ZnO, 2000 ppm, administered from day 21 prior to mating until day 15 of gestation induced no adverse effects on foetal development. This dietary level corresponds to a daily dose of about 100 mg/kg expressed as ZnO, or about 80 mg/kg expressed as zinc which represents the NOEL in this study. Ref. : 29 2.7. Toxicokinetics (incl. Percutaneous Absorption) Method : In vivo, human Volunteers: : 6 healthy males Test substance : ZnO Site of application : Chest, upper and lower legs Exposure : Daily application of 40% ZnO in ointment for a of period 10 days; CITATION=Ref. : 29 2; CITATION_NUMBERS=[29,2]; REFERENCE=Ref. : 29 2; DETAILS_JSON={"cas_number":"1314-13-2","citation":"Ref. : 29 2","dose":"Conclusion ZnO, 2000 ppm, administered from day 21 prior to mating until day 15 of gestation induced no adverse effects on foetal development.","duration":"developmental","effect":"e observed in foetal whole body samples. These analytical results support the interpretation that the observed developmental effects of exaggerated high zinc doses are mediated by depletion of certain essential minerals such as copper. Conclusion ZnO, 2000 ppm, administered from day 21 prior to mating until day 15 of gestation induced no adverse effects on foetal development. This dietary level corresponds to a daily dose of about 100 mg/kg expressed as ZnO, or about 80 mg/kg expressed as zinc which represents the NOEL in this study. Ref. : 29 2.7. Toxicokinetics (incl. Percutaneous Absorption) Method : In vivo, human Volunteers: : 6 healthy males Test substance : ZnO Site of application : Chest, upper and lower legs Exposure : Daily application of 40% ZnO in ointment for a of period 10 days","endpoint":"developmental toxicity","ingredient":"codes","loael_value":"","noael_unit":"%","noael_value":"40","page":14,"route":"oral","species":"human","study_id":"out222_en_noael_006"}
UnifiedCodex:SCCS_SHADOW:beta.noael_studies 27 endpoints
Source Endpoint Type Value Unit Species Route Duration Study Type Reference
UnifiedCodex:SCCS_SHADOW:beta.noael_studies - 1000 mg/kg mouse oral - - SOURCE_SUBDIR=sccs_o_103; REPORT_TITLE=OPINION ON Zinc oxide (nano form) COLIPA S 76; OPINION_NUMBER=SCCS/1489/12; COMMITTEE=Scientific Committee on Consumer Safety (SCCS); REPORT_DATE=11 December 2012; VALUE_TEXT=1,000; DOSE=hip, many effects were noted at the highest dose administered that should be considered dose related even when they only occur at the highest dose.; EFFECT=hip, many effects were noted at the highest dose administered that should be considered dose related even when they only occur at the highest dose. The pathological findings indicate a dose response relationship with the highest dose inducing the most severe alterations. The lowest dose investigated (1,000 mg/kg) also induced pathological effects in the animals. Most effects showed some minor differences between the 20 and 120 nm sized ZnO. Target organs for toxicity were liver, heart, spleen, pancreas and bone. A no observed adverse effect level (NOAEL) was not dentified because alterations were also observed at the lowest dose investigated (1,000 mg/kg). No deaths were observed in a similar study using a single oral dose of 5 mg/kg in mice (Reference: AR16). ZnO nanoparticles were approximately 50 nm in size (TEM evaluation), which were compared to ZnO microparticles showing at least one diameter >100 nm (TEM evaluation). DLS evaluation showed an average hydrodynamic diameter of 1,226 ± 120 nm for the ZnO microparticles, and an average hydrodynamic diame; CITATION=Reference: AR16); CITATION_NUMBERS=[16]; REFERENCE=Reference: AR16); DETAILS_JSON={"cas_number":"1314-13-2","citation":"Reference: AR16)","dose":"hip, many effects were noted at the highest dose administered that should be considered dose related even when they only occur at the highest dose.","duration":"","effect":"hip, many effects were noted at the highest dose administered that should be considered dose related even when they only occur at the highest dose. The pathological findings indicate a dose response relationship with the highest dose inducing the most severe alterations. The lowest dose investigated (1,000 mg/kg) also induced pathological effects in the animals. Most effects showed some minor differences between the 20 and 120 nm sized ZnO. Target organs for toxicity were liver, heart, spleen, pancreas and bone. A no observed adverse effect level (NOAEL) was not dentified because alterations were also observed at the lowest dose investigated (1,000 mg/kg). No deaths were observed in a similar study using a single oral dose of 5 mg/kg in mice (Reference: AR16). ZnO nanoparticles were approximately 50 nm in size (TEM evaluation), which were compared to ZnO microparticles showing at least one diameter >100 nm (TEM evaluation). DLS evaluation showed an average hydrodynamic diameter of 1,226 ± 120 nm for the ZnO microparticles, and an average hydrodynamic diame","endpoint":"","ingredient":"codes.................................... 9","loael_value":"","noael_unit":"mg/kg","noael_value":"1,000","page":29,"route":"oral","species":"mouse","study_id":"sccs_o_103_noael_001"}
UnifiedCodex:SCCS_SHADOW:beta.noael_studies - 1000 mg/kg mouse oral - - SOURCE_SUBDIR=sccs_o_103; REPORT_TITLE=OPINION ON Zinc oxide (nano form) COLIPA S 76; OPINION_NUMBER=SCCS/1489/12; COMMITTEE=Scientific Committee on Consumer Safety (SCCS); REPORT_DATE=11 December 2012; VALUE_TEXT=1,000; DOSE=e highest dose administered that should be considered dose related even when they only occur at the highest dose.; EFFECT=e highest dose administered that should be considered dose related even when they only occur at the highest dose. The pathological findings indicate a dose response relationship with the highest dose inducing the most severe alterations. The lowest dose investigated (1,000 mg/kg) also induced pathological effects in the animals. Most effects showed some minor differences between the 20 and 120 nm sized ZnO. Target organs for toxicity were liver, heart, spleen, pancreas and bone. A no observed adverse effect level (NOAEL) was not dentified because alterations were also observed at the lowest dose investigated (1,000 mg/kg). No deaths were observed in a similar study using a single oral dose of 5 mg/kg in mice (Reference: AR16). ZnO nanoparticles were approximately 50 nm in size (TEM evaluation), which were compared to ZnO microparticles showing at least one diameter >100 nm (TEM evaluation). DLS evaluation showed an average hydrodynamic diameter of 1,226 ± 120 nm for the ZnO microparticles, and an average hydrodynamic diameter of; CITATION=Reference: AR16); CITATION_NUMBERS=[16]; REFERENCE=Reference: AR16); DETAILS_JSON={"cas_number":"1314-13-2","citation":"Reference: AR16)","dose":"e highest dose administered that should be considered dose related even when they only occur at the highest dose.","duration":"","effect":"e highest dose administered that should be considered dose related even when they only occur at the highest dose. The pathological findings indicate a dose response relationship with the highest dose inducing the most severe alterations. The lowest dose investigated (1,000 mg/kg) also induced pathological effects in the animals. Most effects showed some minor differences between the 20 and 120 nm sized ZnO. Target organs for toxicity were liver, heart, spleen, pancreas and bone. A no observed adverse effect level (NOAEL) was not dentified because alterations were also observed at the lowest dose investigated (1,000 mg/kg). No deaths were observed in a similar study using a single oral dose of 5 mg/kg in mice (Reference: AR16). ZnO nanoparticles were approximately 50 nm in size (TEM evaluation), which were compared to ZnO microparticles showing at least one diameter >100 nm (TEM evaluation). DLS evaluation showed an average hydrodynamic diameter of 1,226 ± 120 nm for the ZnO microparticles, and an average hydrodynamic diameter of","endpoint":"","ingredient":"codes.................................... 9","loael_value":"","noael_unit":"mg/kg","noael_value":"1,000","page":29,"route":"oral","species":"mouse","study_id":"sccs_o_103_noael_002"}
UnifiedCodex:SCCS_SHADOW:beta.noael_studies - 20 % human oral - - SOURCE_SUBDIR=sccs_o_103; REPORT_TITLE=OPINION ON Zinc oxide (nano form) COLIPA S 76; OPINION_NUMBER=SCCS/1489/12; COMMITTEE=Scientific Committee on Consumer Safety (SCCS); REPORT_DATE=11 December 2012; VALUE_TEXT=20; DOSE=Given that this study was with women (the most sensitive population in zinc supplementation studies), and that in women clinical signs begin to appear only at a dose three times this NOAEL, a minimal MOS of 1 is considered sufficient when comparing the human NOAEL with the exposure levels for workers/consumers/general population.; EFFECT=mg Zn2+/day by correction for oral absorption (20%; worst case, because of the homeostasis the relative absorption will be smaller by excess of Zn2+-intake). Given that this study was with women (the most sensitive population in zinc supplementation studies), and that in women clinical signs begin to appear only at a dose three times this NOAEL, a minimal MOS of 1 is considered sufficient when comparing the human NOAEL with the exposure levels for workers/consumers/general population. The MOS between this internal NOAEL and the internal exposure as a result of exposure to sunscreen formulations is 5, which is a factor of 5 larger than the minimal MOS. The SCCS agrees with the NOAEL indicated in the RAR statement. Therefore, this information is used together with the data from the absorption study provided in the dossier and exposure assumptions from the SCCS Notes of Guidance for the risk assessment of zinc oxide nanoparticles in sun screens as follows:; CITATION_NUMBERS=[]; DETAILS_JSON={"cas_number":"1314-13-2","citation":"","dose":"Given that this study was with women (the most sensitive population in zinc supplementation studies), and that in women clinical signs begin to appear only at a dose three times this NOAEL, a minimal MOS of 1 is considered sufficient when comparing the human NOAEL with the exposure levels for workers/consumers/general population.","duration":"","effect":"mg Zn2+/day by correction for oral absorption (20%; worst case, because of the homeostasis the relative absorption will be smaller by excess of Zn2+-intake). Given that this study was with women (the most sensitive population in zinc supplementation studies), and that in women clinical signs begin to appear only at a dose three times this NOAEL, a minimal MOS of 1 is considered sufficient when comparing the human NOAEL with the exposure levels for workers/consumers/general population. The MOS between this internal NOAEL and the internal exposure as a result of exposure to sunscreen formulations is 5, which is a factor of 5 larger than the minimal MOS. The SCCS agrees with the NOAEL indicated in the RAR statement. Therefore, this information is used together with the data from the absorption study provided in the dossier and exposure assumptions from the SCCS Notes of Guidance for the risk assessment of zinc oxide nanoparticles in sun screens as follows:","endpoint":"","ingredient":"codes.................................... 9","loael_value":"","noael_unit":"%","noael_value":"20","page":89,"route":"oral","species":"human","study_id":"sccs_o_103_noael_009"}
UnifiedCodex:SCCS_SHADOW:beta.noael_studies - 1 - human - - - SOURCE_SUBDIR=sccs_o_103; REPORT_TITLE=OPINION ON Zinc oxide (nano form) COLIPA S 76; OPINION_NUMBER=SCCS/1489/12; COMMITTEE=Scientific Committee on Consumer Safety (SCCS); REPORT_DATE=11 December 2012; VALUE_TEXT=unclear:t this study was with women (the most sensitive population in zinc supplementation studies), and that in women clinical signs begin to appear only at a dose three times this NOAEL, a minimal MOS of 1 is considered sufficient when comparing the human NOAEL with the exposure levels for workers/consumers/general population. The MOS between this internal NOAEL and the internal exposure as a result of exposure to sunscreen formulations is 5, which is a factor of 5 larger than the minimal MOS. The SCCS agrees with the NOAEL indicated in the RAR statement. Therefore, this information is used together with the data from the absorption study provided in the dossier and exposure assumptions from the SCCS Notes of Guidance for the risk assessment of zinc oxide nanoparticles in sun screens as follows:; DOSE=t this study was with women (the most sensitive population in zinc supplementation studies), and that in women clinical signs begin to appear only at a dose three times this NOAEL, a minimal MOS of 1 is considered sufficient when comparing the human NOAEL with the exposure levels for workers/consumers/general population.; EFFECT=t this study was with women (the most sensitive population in zinc supplementation studies), and that in women clinical signs begin to appear only at a dose three times this NOAEL, a minimal MOS of 1 is considered sufficient when comparing the human NOAEL with the exposure levels for workers/consumers/general population. The MOS between this internal NOAEL and the internal exposure as a result of exposure to sunscreen formulations is 5, which is a factor of 5 larger than the minimal MOS. The SCCS agrees with the NOAEL indicated in the RAR statement. Therefore, this information is used together with the data from the absorption study provided in the dossier and exposure assumptions from the SCCS Notes of Guidance for the risk assessment of zinc oxide nanoparticles in sun screens as follows:; CITATION_NUMBERS=[]; DETAILS_JSON={"cas_number":"1314-13-2","citation":"","dose":"t this study was with women (the most sensitive population in zinc supplementation studies), and that in women clinical signs begin to appear only at a dose three times this NOAEL, a minimal MOS of 1 is considered sufficient when comparing the human NOAEL with the exposure levels for workers/consumers/general population.","duration":"","effect":"t this study was with women (the most sensitive population in zinc supplementation studies), and that in women clinical signs begin to appear only at a dose three times this NOAEL, a minimal MOS of 1 is considered sufficient when comparing the human NOAEL with the exposure levels for workers/consumers/general population. The MOS between this internal NOAEL and the internal exposure as a result of exposure to sunscreen formulations is 5, which is a factor of 5 larger than the minimal MOS. The SCCS agrees with the NOAEL indicated in the RAR statement. Therefore, this information is used together with the data from the absorption study provided in the dossier and exposure assumptions from the SCCS Notes of Guidance for the risk assessment of zinc oxide nanoparticles in sun screens as follows:","endpoint":"","ingredient":"codes.................................... 9","loael_value":"","noael_unit":"","noael_value":"unclear:t this study was with women (the most sensitive population in zinc supplementation studies), and that in women clinical signs begin to appear only at a dose three times this NOAEL, a minimal MOS of 1 is considered sufficient when comparing the human NOAEL with the exposure levels for workers/consumers/general population. The MOS between this internal NOAEL and the internal exposure as a result of exposure to sunscreen formulations is 5, which is a factor of 5 larger than the minimal MOS. The SCCS agrees with the NOAEL indicated in the RAR statement. Therefore, this information is used together with the data from the absorption study provided in the dossier and exposure assumptions from the SCCS Notes of Guidance for the risk assessment of zinc oxide nanoparticles in sun screens as follows:","page":89,"route":"","species":"human","study_id":"sccs_o_103_noael_010"}
UnifiedCodex:SCCS_SHADOW:beta.noael_studies - 0.0225 mg/kg bw/d human oral - - SOURCE_SUBDIR=sccs_o_103; REPORT_TITLE=OPINION ON Zinc oxide (nano form) COLIPA S 76; OPINION_NUMBER=SCCS/1489/12; COMMITTEE=Scientific Committee on Consumer Safety (SCCS); REPORT_DATE=11 December 2012; VALUE_TEXT=0.0225; DOSE=36) Amount absorbed/day (18,000 × 25%/100 × 0.03%/100) 1.35 mg Typical body weight of human 60 kg Systemic exposure dose (1.35 mg/60 kg) 0.0225 mg/kg bw/d No Observed Adverse Effect Level NOAEL (oral, human, sensitive subpopulation)** 0.166 mg/kg bw/d Margin of Safety NOAEL/SED = 7.4 * Standard amount as indicated in the SCCS Notes of Guidance f...; EFFECT=inc oxide (nano form) ___________________________________________________________________________________________ 90 Calculation of the margin of safety for ZnO (nano) (See section 3.1.16 for the range of nano-ZnO covered by this opinion) Amount of sunscreen applied* 18,000 mg Maximum concentration of ZnO 25% Absorption through the skin 0.03% (Reference: 36) Amount absorbed/day (18,000 × 25%/100 × 0.03%/100) 1.35 mg Typical body weight of human 60 kg Systemic exposure dose (1.35 mg/60 kg) 0.0225 mg/kg bw/d No Observed Adverse Effect Level NOAEL (oral, human, sensitive subpopulation)** 0.166 mg/kg bw/d Margin of Safety NOAEL/SED = 7.4 * Standard amount as indicated in the SCCS Notes of Guidance for the testing of cosmetic ingredients and their safety evaluation SCCS/1416/11 ** The internal NOAEL for ZnO is 10 mg Zn2+/day = 10/60= 0.166 mg /kg bw per day (Reference 44, sub III) The calculation of the exposure via sun protection products to ZnO nanoparticles assuming Zn2+ uptake results in a MoS of 7.4. Given that the NOAEL is derived from a study on; CITATION=Reference: 36) Amount absorbed/day (18,000 × 25%/100 × 0; CITATION_NUMBERS=[36,18,25,100]; REFERENCE=Reference: 36) Amount absorbed/day (18,000 × 25%/100 × 0; DETAILS_JSON={"cas_number":"1314-13-2","citation":"Reference: 36) Amount absorbed/day (18,000 × 25%/100 × 0","dose":"36) Amount absorbed/day (18,000 × 25%/100 × 0.03%/100) 1.35 mg Typical body weight of human 60 kg Systemic exposure dose (1.35 mg/60 kg) 0.0225 mg/kg bw/d No Observed Adverse Effect Level NOAEL (oral, human, sensitive subpopulation)** 0.166 mg/kg bw/d Margin of Safety NOAEL/SED = 7.4 * Standard amount as indicated in the SCCS Notes of Guidance f...","duration":"","effect":"inc oxide (nano form) ___________________________________________________________________________________________ 90 Calculation of the margin of safety for ZnO (nano) (See section 3.1.16 for the range of nano-ZnO covered by this opinion) Amount of sunscreen applied* 18,000 mg Maximum concentration of ZnO 25% Absorption through the skin 0.03% (Reference: 36) Amount absorbed/day (18,000 × 25%/100 × 0.03%/100) 1.35 mg Typical body weight of human 60 kg Systemic exposure dose (1.35 mg/60 kg) 0.0225 mg/kg bw/d No Observed Adverse Effect Level NOAEL (oral, human, sensitive subpopulation)** 0.166 mg/kg bw/d Margin of Safety NOAEL/SED = 7.4 * Standard amount as indicated in the SCCS Notes of Guidance for the testing of cosmetic ingredients and their safety evaluation SCCS/1416/11 ** The internal NOAEL for ZnO is 10 mg Zn2+/day = 10/60= 0.166 mg /kg bw per day (Reference 44, sub III) The calculation of the exposure via sun protection products to ZnO nanoparticles assuming Zn2+ uptake results in a MoS of 7.4. Given that the NOAEL is derived from a study on","endpoint":"","ingredient":"codes.................................... 9","loael_value":"","noael_unit":"mg/kg bw/d","noael_value":"0.0225","page":90,"route":"oral","species":"human","study_id":"sccs_o_103_noael_011"}
UnifiedCodex:SCCS_SHADOW:beta.noael_studies - 0.166 mg/kg bw/d human oral - - SOURCE_SUBDIR=sccs_o_103; REPORT_TITLE=OPINION ON Zinc oxide (nano form) COLIPA S 76; OPINION_NUMBER=SCCS/1489/12; COMMITTEE=Scientific Committee on Consumer Safety (SCCS); REPORT_DATE=11 December 2012; VALUE_TEXT=0.166; DOSE=36) Amount absorbed/day (18,000 × 25%/100 × 0.03%/100) 1.35 mg Typical body weight of human 60 kg Systemic exposure dose (1.35 mg/60 kg) 0.0225 mg/kg bw/d No Observed Adverse Effect Level NOAEL (oral, human, sensitive subpopulation)** 0.166 mg/kg bw/d Margin of Safety NOAEL/SED = 7.4 * Standard amount as indicated in the SCCS Notes of Guidance f...; EFFECT=________________________________________________________________________________ 90 Calculation of the margin of safety for ZnO (nano) (See section 3.1.16 for the range of nano-ZnO covered by this opinion) Amount of sunscreen applied* 18,000 mg Maximum concentration of ZnO 25% Absorption through the skin 0.03% (Reference: 36) Amount absorbed/day (18,000 × 25%/100 × 0.03%/100) 1.35 mg Typical body weight of human 60 kg Systemic exposure dose (1.35 mg/60 kg) 0.0225 mg/kg bw/d No Observed Adverse Effect Level NOAEL (oral, human, sensitive subpopulation)** 0.166 mg/kg bw/d Margin of Safety NOAEL/SED = 7.4 * Standard amount as indicated in the SCCS Notes of Guidance for the testing of cosmetic ingredients and their safety evaluation SCCS/1416/11 ** The internal NOAEL for ZnO is 10 mg Zn2+/day = 10/60= 0.166 mg /kg bw per day (Reference 44, sub III) The calculation of the exposure via sun protection products to ZnO nanoparticles assuming Zn2+ uptake results in a MoS of 7.4. Given that the NOAEL is derived from a study on women; CITATION=Reference: 36) Amount absorbed/day (18,000 × 25%/100 × 0; CITATION_NUMBERS=[36,18,25,100]; REFERENCE=Reference: 36) Amount absorbed/day (18,000 × 25%/100 × 0; DETAILS_JSON={"cas_number":"1314-13-2","citation":"Reference: 36) Amount absorbed/day (18,000 × 25%/100 × 0","dose":"36) Amount absorbed/day (18,000 × 25%/100 × 0.03%/100) 1.35 mg Typical body weight of human 60 kg Systemic exposure dose (1.35 mg/60 kg) 0.0225 mg/kg bw/d No Observed Adverse Effect Level NOAEL (oral, human, sensitive subpopulation)** 0.166 mg/kg bw/d Margin of Safety NOAEL/SED = 7.4 * Standard amount as indicated in the SCCS Notes of Guidance f...","duration":"","effect":"________________________________________________________________________________ 90 Calculation of the margin of safety for ZnO (nano) (See section 3.1.16 for the range of nano-ZnO covered by this opinion) Amount of sunscreen applied* 18,000 mg Maximum concentration of ZnO 25% Absorption through the skin 0.03% (Reference: 36) Amount absorbed/day (18,000 × 25%/100 × 0.03%/100) 1.35 mg Typical body weight of human 60 kg Systemic exposure dose (1.35 mg/60 kg) 0.0225 mg/kg bw/d No Observed Adverse Effect Level NOAEL (oral, human, sensitive subpopulation)** 0.166 mg/kg bw/d Margin of Safety NOAEL/SED = 7.4 * Standard amount as indicated in the SCCS Notes of Guidance for the testing of cosmetic ingredients and their safety evaluation SCCS/1416/11 ** The internal NOAEL for ZnO is 10 mg Zn2+/day = 10/60= 0.166 mg /kg bw per day (Reference 44, sub III) The calculation of the exposure via sun protection products to ZnO nanoparticles assuming Zn2+ uptake results in a MoS of 7.4. Given that the NOAEL is derived from a study on women","endpoint":"","ingredient":"codes.................................... 9","loael_value":"","noael_unit":"mg/kg bw/d","noael_value":"0.166","page":90,"route":"oral","species":"human","study_id":"sccs_o_103_noael_012"}
UnifiedCodex:SCCS_SHADOW:beta.noael_studies - 0.166 mg/kg bw/d human oral - - SOURCE_SUBDIR=sccs_o_103; REPORT_TITLE=OPINION ON Zinc oxide (nano form) COLIPA S 76; OPINION_NUMBER=SCCS/1489/12; COMMITTEE=Scientific Committee on Consumer Safety (SCCS); REPORT_DATE=11 December 2012; VALUE_TEXT=0.166; DOSE=36) Amount absorbed/day (18,000 × 25%/100 × 0.03%/100) 1.35 mg Typical body weight of human 60 kg Systemic exposure dose (1.35 mg/60 kg) 0.0225 mg/kg bw/d No Observed Adverse Effect Level NOAEL (oral, human, sensitive subpopulation)** 0.166 mg/kg bw/d Margin of Safety NOAEL/SED = 7.4 * Standard amount as indicated in the SCCS Notes of Guidance f...; EFFECT=90 Calculation of the margin of safety for ZnO (nano) (See section 3.1.16 for the range of nano-ZnO covered by this opinion) Amount of sunscreen applied* 18,000 mg Maximum concentration of ZnO 25% Absorption through the skin 0.03% (Reference: 36) Amount absorbed/day (18,000 × 25%/100 × 0.03%/100) 1.35 mg Typical body weight of human 60 kg Systemic exposure dose (1.35 mg/60 kg) 0.0225 mg/kg bw/d No Observed Adverse Effect Level NOAEL (oral, human, sensitive subpopulation)** 0.166 mg/kg bw/d Margin of Safety NOAEL/SED = 7.4 * Standard amount as indicated in the SCCS Notes of Guidance for the testing of cosmetic ingredients and their safety evaluation SCCS/1416/11 ** The internal NOAEL for ZnO is 10 mg Zn2+/day = 10/60= 0.166 mg /kg bw per day (Reference 44, sub III) The calculation of the exposure via sun protection products to ZnO nanoparticles assuming Zn2+ uptake results in a MoS of 7.4. Given that the NOAEL is derived from a study on women (the most sensitive population in zinc supplementation studies), and that in wom; CITATION=Reference: 36) Amount absorbed/day (18,000 × 25%/100 × 0; CITATION_NUMBERS=[36,18,25,100]; REFERENCE=Reference: 36) Amount absorbed/day (18,000 × 25%/100 × 0; DETAILS_JSON={"cas_number":"1314-13-2","citation":"Reference: 36) Amount absorbed/day (18,000 × 25%/100 × 0","dose":"36) Amount absorbed/day (18,000 × 25%/100 × 0.03%/100) 1.35 mg Typical body weight of human 60 kg Systemic exposure dose (1.35 mg/60 kg) 0.0225 mg/kg bw/d No Observed Adverse Effect Level NOAEL (oral, human, sensitive subpopulation)** 0.166 mg/kg bw/d Margin of Safety NOAEL/SED = 7.4 * Standard amount as indicated in the SCCS Notes of Guidance f...","duration":"","effect":"90 Calculation of the margin of safety for ZnO (nano) (See section 3.1.16 for the range of nano-ZnO covered by this opinion) Amount of sunscreen applied* 18,000 mg Maximum concentration of ZnO 25% Absorption through the skin 0.03% (Reference: 36) Amount absorbed/day (18,000 × 25%/100 × 0.03%/100) 1.35 mg Typical body weight of human 60 kg Systemic exposure dose (1.35 mg/60 kg) 0.0225 mg/kg bw/d No Observed Adverse Effect Level NOAEL (oral, human, sensitive subpopulation)** 0.166 mg/kg bw/d Margin of Safety NOAEL/SED = 7.4 * Standard amount as indicated in the SCCS Notes of Guidance for the testing of cosmetic ingredients and their safety evaluation SCCS/1416/11 ** The internal NOAEL for ZnO is 10 mg Zn2+/day = 10/60= 0.166 mg /kg bw per day (Reference 44, sub III) The calculation of the exposure via sun protection products to ZnO nanoparticles assuming Zn2+ uptake results in a MoS of 7.4. Given that the NOAEL is derived from a study on women (the most sensitive population in zinc supplementation studies), and that in wom","endpoint":"","ingredient":"codes.................................... 9","loael_value":"","noael_unit":"mg/kg bw/d","noael_value":"0.166","page":90,"route":"oral","species":"human","study_id":"sccs_o_103_noael_013"}
UnifiedCodex:SCCS_SHADOW:beta.noael_studies - =0.166 mg /kg bw human oral - - SOURCE_SUBDIR=sccs_o_103; REPORT_TITLE=OPINION ON Zinc oxide (nano form) COLIPA S 76; OPINION_NUMBER=SCCS/1489/12; COMMITTEE=Scientific Committee on Consumer Safety (SCCS); REPORT_DATE=11 December 2012; VALUE_TEXT== 0.166; DOSE=36) Amount absorbed/day (18,000 × 25%/100 × 0.03%/100) 1.35 mg Typical body weight of human 60 kg Systemic exposure dose (1.35 mg/60 kg) 0.0225 mg/kg bw/d No Observed Adverse Effect Level NOAEL (oral, human, sensitive subpopulation)** 0.166 mg/kg bw/d Margin of Safety NOAEL/SED = 7.4 * Standard amount as indicated in the SCCS Notes of Guidance f...; EFFECT=concentration of ZnO 25% Absorption through the skin 0.03% (Reference: 36) Amount absorbed/day (18,000 × 25%/100 × 0.03%/100) 1.35 mg Typical body weight of human 60 kg Systemic exposure dose (1.35 mg/60 kg) 0.0225 mg/kg bw/d No Observed Adverse Effect Level NOAEL (oral, human, sensitive subpopulation)** 0.166 mg/kg bw/d Margin of Safety NOAEL/SED = 7.4 * Standard amount as indicated in the SCCS Notes of Guidance for the testing of cosmetic ingredients and their safety evaluation SCCS/1416/11 ** The internal NOAEL for ZnO is 10 mg Zn2+/day = 10/60= 0.166 mg /kg bw per day (Reference 44, sub III) The calculation of the exposure via sun protection products to ZnO nanoparticles assuming Zn2+ uptake results in a MoS of 7.4. Given that the NOAEL is derived from a study on women (the most sensitive population in zinc supplementation studies), and that in women clinical signs begin to appear only at a dose three times this NOAEL, a minimal MOS of 1 is considered sufficient when comparing the human NOAEL with the exposure levels f; CITATION=Reference: 36) Amount absorbed/day (18,000 × 25%/100 × 0; CITATION_NUMBERS=[36,18,25,100]; REFERENCE=Reference: 36) Amount absorbed/day (18,000 × 25%/100 × 0; DETAILS_JSON={"cas_number":"1314-13-2","citation":"Reference: 36) Amount absorbed/day (18,000 × 25%/100 × 0","dose":"36) Amount absorbed/day (18,000 × 25%/100 × 0.03%/100) 1.35 mg Typical body weight of human 60 kg Systemic exposure dose (1.35 mg/60 kg) 0.0225 mg/kg bw/d No Observed Adverse Effect Level NOAEL (oral, human, sensitive subpopulation)** 0.166 mg/kg bw/d Margin of Safety NOAEL/SED = 7.4 * Standard amount as indicated in the SCCS Notes of Guidance f...","duration":"","effect":"concentration of ZnO 25% Absorption through the skin 0.03% (Reference: 36) Amount absorbed/day (18,000 × 25%/100 × 0.03%/100) 1.35 mg Typical body weight of human 60 kg Systemic exposure dose (1.35 mg/60 kg) 0.0225 mg/kg bw/d No Observed Adverse Effect Level NOAEL (oral, human, sensitive subpopulation)** 0.166 mg/kg bw/d Margin of Safety NOAEL/SED = 7.4 * Standard amount as indicated in the SCCS Notes of Guidance for the testing of cosmetic ingredients and their safety evaluation SCCS/1416/11 ** The internal NOAEL for ZnO is 10 mg Zn2+/day = 10/60= 0.166 mg /kg bw per day (Reference 44, sub III) The calculation of the exposure via sun protection products to ZnO nanoparticles assuming Zn2+ uptake results in a MoS of 7.4. Given that the NOAEL is derived from a study on women (the most sensitive population in zinc supplementation studies), and that in women clinical signs begin to appear only at a dose three times this NOAEL, a minimal MOS of 1 is considered sufficient when comparing the human NOAEL with the exposure levels f","endpoint":"","ingredient":"codes.................................... 9","loael_value":"","noael_unit":"mg /kg bw","noael_value":"= 0.166","page":90,"route":"oral","species":"human","study_id":"sccs_o_103_noael_014"}
UnifiedCodex:SCCS_SHADOW:beta.noael_studies - =0.166 mg /kg bw human oral - - SOURCE_SUBDIR=sccs_o_103; REPORT_TITLE=OPINION ON Zinc oxide (nano form) COLIPA S 76; OPINION_NUMBER=SCCS/1489/12; COMMITTEE=Scientific Committee on Consumer Safety (SCCS); REPORT_DATE=11 December 2012; VALUE_TEXT== 0.166; DOSE=No Observed Adverse Effect Level NOAEL (oral, human, sensitive subpopulation)** 0.166 mg/kg bw/d Margin of Safety NOAEL/SED = 7.4 * Standard amount as indicated in the SCCS Notes of Guidance for the testing of cosmetic ingredients and their safety evaluation SCCS/1416/11 ** The internal NOAEL for ZnO is 10 mg Zn2+/day = 10/60= 0.166 mg /kg bw pe...; EFFECT=No Observed Adverse Effect Level NOAEL (oral, human, sensitive subpopulation)** 0.166 mg/kg bw/d Margin of Safety NOAEL/SED = 7.4 * Standard amount as indicated in the SCCS Notes of Guidance for the testing of cosmetic ingredients and their safety evaluation SCCS/1416/11 ** The internal NOAEL for ZnO is 10 mg Zn2+/day = 10/60= 0.166 mg /kg bw per day (Reference 44, sub III) The calculation of the exposure via sun protection products to ZnO nanoparticles assuming Zn2+ uptake results in a MoS of 7.4. Given that the NOAEL is derived from a study on women (the most sensitive population in zinc supplementation studies), and that in women clinical signs begin to appear only at a dose three times this NOAEL, a minimal MOS of 1 is considered sufficient when comparing the human NOAEL with the exposure levels for workers/consumers/general population (Reference 44, sub III). Calculation of the Margin of Safety for Lip products According to the SCCS Notes of Guidance for the testing of cosmetic ingredients and their safety evaluation (SCCS; CITATION=(Reference 44, sub III); CITATION_NUMBERS=[44]; REFERENCE=(Reference 44, sub III); DETAILS_JSON={"cas_number":"1314-13-2","citation":"(Reference 44, sub III)","dose":"No Observed Adverse Effect Level NOAEL (oral, human, sensitive subpopulation)** 0.166 mg/kg bw/d Margin of Safety NOAEL/SED = 7.4 * Standard amount as indicated in the SCCS Notes of Guidance for the testing of cosmetic ingredients and their safety evaluation SCCS/1416/11 ** The internal NOAEL for ZnO is 10 mg Zn2+/day = 10/60= 0.166 mg /kg bw pe...","duration":"","effect":"No Observed Adverse Effect Level NOAEL (oral, human, sensitive subpopulation)** 0.166 mg/kg bw/d Margin of Safety NOAEL/SED = 7.4 * Standard amount as indicated in the SCCS Notes of Guidance for the testing of cosmetic ingredients and their safety evaluation SCCS/1416/11 ** The internal NOAEL for ZnO is 10 mg Zn2+/day = 10/60= 0.166 mg /kg bw per day (Reference 44, sub III) The calculation of the exposure via sun protection products to ZnO nanoparticles assuming Zn2+ uptake results in a MoS of 7.4. Given that the NOAEL is derived from a study on women (the most sensitive population in zinc supplementation studies), and that in women clinical signs begin to appear only at a dose three times this NOAEL, a minimal MOS of 1 is considered sufficient when comparing the human NOAEL with the exposure levels for workers/consumers/general population (Reference 44, sub III). Calculation of the Margin of Safety for Lip products According to the SCCS Notes of Guidance for the testing of cosmetic ingredients and their safety evaluation (SCCS","endpoint":"","ingredient":"codes.................................... 9","loael_value":"","noael_unit":"mg /kg bw","noael_value":"= 0.166","page":90,"route":"oral","species":"human","study_id":"sccs_o_103_noael_015"}
UnifiedCodex:SCCS_SHADOW:beta.noael_studies - =0.166 mg /kg bw human oral - - SOURCE_SUBDIR=sccs_o_103; REPORT_TITLE=OPINION ON Zinc oxide (nano form) COLIPA S 76; OPINION_NUMBER=SCCS/1489/12; COMMITTEE=Scientific Committee on Consumer Safety (SCCS); REPORT_DATE=11 December 2012; VALUE_TEXT== 0.166; DOSE=dance for the testing of cosmetic ingredients and their safety evaluation SCCS/1416/11 ** The internal NOAEL for ZnO is 10 mg Zn2+/day = 10/60= 0.166 mg /kg bw per day (Reference 44, sub III) The calculation of the exposure via sun protection products to ZnO nanoparticles assuming Zn2+ uptake results in a MoS of 7.4.; EFFECT=dance for the testing of cosmetic ingredients and their safety evaluation SCCS/1416/11 ** The internal NOAEL for ZnO is 10 mg Zn2+/day = 10/60= 0.166 mg /kg bw per day (Reference 44, sub III) The calculation of the exposure via sun protection products to ZnO nanoparticles assuming Zn2+ uptake results in a MoS of 7.4. Given that the NOAEL is derived from a study on women (the most sensitive population in zinc supplementation studies), and that in women clinical signs begin to appear only at a dose three times this NOAEL, a minimal MOS of 1 is considered sufficient when comparing the human NOAEL with the exposure levels for workers/consumers/general population (Reference 44, sub III). Calculation of the Margin of Safety for Lip products According to the SCCS Notes of Guidance for the testing of cosmetic ingredients and their safety evaluation (SCCS/1416/11) the daily exposure to lipstick/lipproducts is 0.9 mg/kg/d. Exposure dose (0.9 x 25%) 0.225 mg/kg bw/day. No Observed Adverse Effect Level NOAEL (oral, human)* 0.83 mg/kg bw/; CITATION=(Reference 44, sub III); CITATION_NUMBERS=[44]; REFERENCE=(Reference 44, sub III); DETAILS_JSON={"cas_number":"1314-13-2","citation":"(Reference 44, sub III)","dose":"dance for the testing of cosmetic ingredients and their safety evaluation SCCS/1416/11 ** The internal NOAEL for ZnO is 10 mg Zn2+/day = 10/60= 0.166 mg /kg bw per day (Reference 44, sub III) The calculation of the exposure via sun protection products to ZnO nanoparticles assuming Zn2+ uptake results in a MoS of 7.4.","duration":"","effect":"dance for the testing of cosmetic ingredients and their safety evaluation SCCS/1416/11 ** The internal NOAEL for ZnO is 10 mg Zn2+/day = 10/60= 0.166 mg /kg bw per day (Reference 44, sub III) The calculation of the exposure via sun protection products to ZnO nanoparticles assuming Zn2+ uptake results in a MoS of 7.4. Given that the NOAEL is derived from a study on women (the most sensitive population in zinc supplementation studies), and that in women clinical signs begin to appear only at a dose three times this NOAEL, a minimal MOS of 1 is considered sufficient when comparing the human NOAEL with the exposure levels for workers/consumers/general population (Reference 44, sub III). Calculation of the Margin of Safety for Lip products According to the SCCS Notes of Guidance for the testing of cosmetic ingredients and their safety evaluation (SCCS/1416/11) the daily exposure to lipstick/lipproducts is 0.9 mg/kg/d. Exposure dose (0.9 x 25%) 0.225 mg/kg bw/day. No Observed Adverse Effect Level NOAEL (oral, human)* 0.83 mg/kg bw/","endpoint":"","ingredient":"codes.................................... 9","loael_value":"","noael_unit":"mg /kg bw","noael_value":"= 0.166","page":90,"route":"oral","species":"human","study_id":"sccs_o_103_noael_016"}
UnifiedCodex:SCCS_SHADOW:beta.noael_studies - 0.9 mg/kg/d human oral - - SOURCE_SUBDIR=sccs_o_103; REPORT_TITLE=OPINION ON Zinc oxide (nano form) COLIPA S 76; OPINION_NUMBER=SCCS/1489/12; COMMITTEE=Scientific Committee on Consumer Safety (SCCS); REPORT_DATE=11 December 2012; VALUE_TEXT=0.9; DOSE=CS/1416/11 ** The internal NOAEL for ZnO is 10 mg Zn2+/day = 10/60= 0.166 mg /kg bw per day (Reference 44, sub III) The calculation of the exposure via sun protection products to ZnO nanoparticles assuming Zn2+ uptake results in a MoS of 7.4.; EFFECT=CS/1416/11 ** The internal NOAEL for ZnO is 10 mg Zn2+/day = 10/60= 0.166 mg /kg bw per day (Reference 44, sub III) The calculation of the exposure via sun protection products to ZnO nanoparticles assuming Zn2+ uptake results in a MoS of 7.4. Given that the NOAEL is derived from a study on women (the most sensitive population in zinc supplementation studies), and that in women clinical signs begin to appear only at a dose three times this NOAEL, a minimal MOS of 1 is considered sufficient when comparing the human NOAEL with the exposure levels for workers/consumers/general population (Reference 44, sub III). Calculation of the Margin of Safety for Lip products According to the SCCS Notes of Guidance for the testing of cosmetic ingredients and their safety evaluation (SCCS/1416/11) the daily exposure to lipstick/lipproducts is 0.9 mg/kg/d. Exposure dose (0.9 x 25%) 0.225 mg/kg bw/day. No Observed Adverse Effect Level NOAEL (oral, human)* 0.83 mg/kg bw/d Margin of Safety NOAEL/ED** = 3.7 * The NOAEL for ZnO is 50 mg Zn2+/day =; CITATION=(Reference 44, sub III); CITATION_NUMBERS=[44]; REFERENCE=(Reference 44, sub III); DETAILS_JSON={"cas_number":"1314-13-2","citation":"(Reference 44, sub III)","dose":"CS/1416/11 ** The internal NOAEL for ZnO is 10 mg Zn2+/day = 10/60= 0.166 mg /kg bw per day (Reference 44, sub III) The calculation of the exposure via sun protection products to ZnO nanoparticles assuming Zn2+ uptake results in a MoS of 7.4.","duration":"","effect":"CS/1416/11 ** The internal NOAEL for ZnO is 10 mg Zn2+/day = 10/60= 0.166 mg /kg bw per day (Reference 44, sub III) The calculation of the exposure via sun protection products to ZnO nanoparticles assuming Zn2+ uptake results in a MoS of 7.4. Given that the NOAEL is derived from a study on women (the most sensitive population in zinc supplementation studies), and that in women clinical signs begin to appear only at a dose three times this NOAEL, a minimal MOS of 1 is considered sufficient when comparing the human NOAEL with the exposure levels for workers/consumers/general population (Reference 44, sub III). Calculation of the Margin of Safety for Lip products According to the SCCS Notes of Guidance for the testing of cosmetic ingredients and their safety evaluation (SCCS/1416/11) the daily exposure to lipstick/lipproducts is 0.9 mg/kg/d. Exposure dose (0.9 x 25%) 0.225 mg/kg bw/day. No Observed Adverse Effect Level NOAEL (oral, human)* 0.83 mg/kg bw/d Margin of Safety NOAEL/ED** = 3.7 * The NOAEL for ZnO is 50 mg Zn2+/day =","endpoint":"","ingredient":"codes.................................... 9","loael_value":"","noael_unit":"mg/kg/d","noael_value":"0.9","page":90,"route":"oral","species":"human","study_id":"sccs_o_103_noael_017"}
UnifiedCodex:SCCS_SHADOW:beta.noael_studies - 0.225 mg/kg bw/day human oral - - SOURCE_SUBDIR=sccs_o_103; REPORT_TITLE=OPINION ON Zinc oxide (nano form) COLIPA S 76; OPINION_NUMBER=SCCS/1489/12; COMMITTEE=Scientific Committee on Consumer Safety (SCCS); REPORT_DATE=11 December 2012; VALUE_TEXT=0.225; DOSE=clinical signs begin to appear only at a dose three times this NOAEL, a minimal MOS of 1 is considered sufficient when comparing the human NOAEL with the exposure levels for workers/consumers/general population (Reference 44, sub III).; EFFECT=clinical signs begin to appear only at a dose three times this NOAEL, a minimal MOS of 1 is considered sufficient when comparing the human NOAEL with the exposure levels for workers/consumers/general population (Reference 44, sub III). Calculation of the Margin of Safety for Lip products According to the SCCS Notes of Guidance for the testing of cosmetic ingredients and their safety evaluation (SCCS/1416/11) the daily exposure to lipstick/lipproducts is 0.9 mg/kg/d. Exposure dose (0.9 x 25%) 0.225 mg/kg bw/day. No Observed Adverse Effect Level NOAEL (oral, human)* 0.83 mg/kg bw/d Margin of Safety NOAEL/ED** = 3.7 * The NOAEL for ZnO is 50 mg Zn2+/day = 50/60= 0.83 mg /kg bw per day (Reference 44, sub III) ** Since route to route extrapolation is not needed, the (external) NOAEL is compared to the (external) exposure dose It is expected that the exposure to lipstick/lip products that contain high SPF factors (eg ZnO nanomaterial) is less than the exposure to ‘regular’ lipstick/lip products. Typically, these products are used only in specific time fram; CITATION=(Reference 44, sub III); CITATION_NUMBERS=[44]; REFERENCE=(Reference 44, sub III); DETAILS_JSON={"cas_number":"1314-13-2","citation":"(Reference 44, sub III)","dose":"clinical signs begin to appear only at a dose three times this NOAEL, a minimal MOS of 1 is considered sufficient when comparing the human NOAEL with the exposure levels for workers/consumers/general population (Reference 44, sub III).","duration":"","effect":"clinical signs begin to appear only at a dose three times this NOAEL, a minimal MOS of 1 is considered sufficient when comparing the human NOAEL with the exposure levels for workers/consumers/general population (Reference 44, sub III). Calculation of the Margin of Safety for Lip products According to the SCCS Notes of Guidance for the testing of cosmetic ingredients and their safety evaluation (SCCS/1416/11) the daily exposure to lipstick/lipproducts is 0.9 mg/kg/d. Exposure dose (0.9 x 25%) 0.225 mg/kg bw/day. No Observed Adverse Effect Level NOAEL (oral, human)* 0.83 mg/kg bw/d Margin of Safety NOAEL/ED** = 3.7 * The NOAEL for ZnO is 50 mg Zn2+/day = 50/60= 0.83 mg /kg bw per day (Reference 44, sub III) ** Since route to route extrapolation is not needed, the (external) NOAEL is compared to the (external) exposure dose It is expected that the exposure to lipstick/lip products that contain high SPF factors (eg ZnO nanomaterial) is less than the exposure to ‘regular’ lipstick/lip products. Typically, these products are used only in specific time fram","endpoint":"","ingredient":"codes.................................... 9","loael_value":"","noael_unit":"mg/kg bw/day","noael_value":"0.225","page":90,"route":"oral","species":"human","study_id":"sccs_o_103_noael_018"}
UnifiedCodex:SCCS_SHADOW:beta.noael_studies - 0.83 mg/kg bw/d human oral - - SOURCE_SUBDIR=sccs_o_103; REPORT_TITLE=OPINION ON Zinc oxide (nano form) COLIPA S 76; OPINION_NUMBER=SCCS/1489/12; COMMITTEE=Scientific Committee on Consumer Safety (SCCS); REPORT_DATE=11 December 2012; VALUE_TEXT=0.83; DOSE=nly at a dose three times this NOAEL, a minimal MOS of 1 is considered sufficient when comparing the human NOAEL with the exposure levels for workers/consumers/general population (Reference 44, sub III).; EFFECT=nly at a dose three times this NOAEL, a minimal MOS of 1 is considered sufficient when comparing the human NOAEL with the exposure levels for workers/consumers/general population (Reference 44, sub III). Calculation of the Margin of Safety for Lip products According to the SCCS Notes of Guidance for the testing of cosmetic ingredients and their safety evaluation (SCCS/1416/11) the daily exposure to lipstick/lipproducts is 0.9 mg/kg/d. Exposure dose (0.9 x 25%) 0.225 mg/kg bw/day. No Observed Adverse Effect Level NOAEL (oral, human)* 0.83 mg/kg bw/d Margin of Safety NOAEL/ED** = 3.7 * The NOAEL for ZnO is 50 mg Zn2+/day = 50/60= 0.83 mg /kg bw per day (Reference 44, sub III) ** Since route to route extrapolation is not needed, the (external) NOAEL is compared to the (external) exposure dose It is expected that the exposure to lipstick/lip products that contain high SPF factors (eg ZnO nanomaterial) is less than the exposure to ‘regular’ lipstick/lip products. Typically, these products are used only in specific time frames, e.; CITATION=(Reference 44, sub III); CITATION_NUMBERS=[44]; REFERENCE=(Reference 44, sub III); DETAILS_JSON={"cas_number":"1314-13-2","citation":"(Reference 44, sub III)","dose":"nly at a dose three times this NOAEL, a minimal MOS of 1 is considered sufficient when comparing the human NOAEL with the exposure levels for workers/consumers/general population (Reference 44, sub III).","duration":"","effect":"nly at a dose three times this NOAEL, a minimal MOS of 1 is considered sufficient when comparing the human NOAEL with the exposure levels for workers/consumers/general population (Reference 44, sub III). Calculation of the Margin of Safety for Lip products According to the SCCS Notes of Guidance for the testing of cosmetic ingredients and their safety evaluation (SCCS/1416/11) the daily exposure to lipstick/lipproducts is 0.9 mg/kg/d. Exposure dose (0.9 x 25%) 0.225 mg/kg bw/day. No Observed Adverse Effect Level NOAEL (oral, human)* 0.83 mg/kg bw/d Margin of Safety NOAEL/ED** = 3.7 * The NOAEL for ZnO is 50 mg Zn2+/day = 50/60= 0.83 mg /kg bw per day (Reference 44, sub III) ** Since route to route extrapolation is not needed, the (external) NOAEL is compared to the (external) exposure dose It is expected that the exposure to lipstick/lip products that contain high SPF factors (eg ZnO nanomaterial) is less than the exposure to ‘regular’ lipstick/lip products. Typically, these products are used only in specific time frames, e.","endpoint":"","ingredient":"codes.................................... 9","loael_value":"","noael_unit":"mg/kg bw/d","noael_value":"0.83","page":90,"route":"oral","species":"human","study_id":"sccs_o_103_noael_019"}
UnifiedCodex:SCCS_SHADOW:beta.noael_studies - 0.83 mg/kg bw/d human oral - - SOURCE_SUBDIR=sccs_o_103; REPORT_TITLE=OPINION ON Zinc oxide (nano form) COLIPA S 76; OPINION_NUMBER=SCCS/1489/12; COMMITTEE=Scientific Committee on Consumer Safety (SCCS); REPORT_DATE=11 December 2012; VALUE_TEXT=0.83; DOSE=Calculation of the Margin of Safety for Lip products According to the SCCS Notes of Guidance for the testing of cosmetic ingredients and their safety evaluation (SCCS/1416/11) the daily exposure to lipstick/lipproducts is 0.9 mg/kg/d.; EFFECT=is considered sufficient when comparing the human NOAEL with the exposure levels for workers/consumers/general population (Reference 44, sub III). Calculation of the Margin of Safety for Lip products According to the SCCS Notes of Guidance for the testing of cosmetic ingredients and their safety evaluation (SCCS/1416/11) the daily exposure to lipstick/lipproducts is 0.9 mg/kg/d. Exposure dose (0.9 x 25%) 0.225 mg/kg bw/day. No Observed Adverse Effect Level NOAEL (oral, human)* 0.83 mg/kg bw/d Margin of Safety NOAEL/ED** = 3.7 * The NOAEL for ZnO is 50 mg Zn2+/day = 50/60= 0.83 mg /kg bw per day (Reference 44, sub III) ** Since route to route extrapolation is not needed, the (external) NOAEL is compared to the (external) exposure dose It is expected that the exposure to lipstick/lip products that contain high SPF factors (eg ZnO nanomaterial) is less than the exposure to ‘regular’ lipstick/lip products. Typically, these products are used only in specific time frames, e.g. during outdoor holidays. Therefore 0.9 mg/kg bw/d is; CITATION=(Reference 44, sub III); CITATION_NUMBERS=[44]; REFERENCE=(Reference 44, sub III); DETAILS_JSON={"cas_number":"1314-13-2","citation":"(Reference 44, sub III)","dose":"Calculation of the Margin of Safety for Lip products According to the SCCS Notes of Guidance for the testing of cosmetic ingredients and their safety evaluation (SCCS/1416/11) the daily exposure to lipstick/lipproducts is 0.9 mg/kg/d.","duration":"","effect":"is considered sufficient when comparing the human NOAEL with the exposure levels for workers/consumers/general population (Reference 44, sub III). Calculation of the Margin of Safety for Lip products According to the SCCS Notes of Guidance for the testing of cosmetic ingredients and their safety evaluation (SCCS/1416/11) the daily exposure to lipstick/lipproducts is 0.9 mg/kg/d. Exposure dose (0.9 x 25%) 0.225 mg/kg bw/day. No Observed Adverse Effect Level NOAEL (oral, human)* 0.83 mg/kg bw/d Margin of Safety NOAEL/ED** = 3.7 * The NOAEL for ZnO is 50 mg Zn2+/day = 50/60= 0.83 mg /kg bw per day (Reference 44, sub III) ** Since route to route extrapolation is not needed, the (external) NOAEL is compared to the (external) exposure dose It is expected that the exposure to lipstick/lip products that contain high SPF factors (eg ZnO nanomaterial) is less than the exposure to ‘regular’ lipstick/lip products. Typically, these products are used only in specific time frames, e.g. during outdoor holidays. Therefore 0.9 mg/kg bw/d is","endpoint":"","ingredient":"codes.................................... 9","loael_value":"","noael_unit":"mg/kg bw/d","noael_value":"0.83","page":90,"route":"oral","species":"human","study_id":"sccs_o_103_noael_020"}
UnifiedCodex:SCCS_SHADOW:beta.noael_studies - =0.83 mg /kg bw human oral - - SOURCE_SUBDIR=sccs_o_103; REPORT_TITLE=OPINION ON Zinc oxide (nano form) COLIPA S 76; OPINION_NUMBER=SCCS/1489/12; COMMITTEE=Scientific Committee on Consumer Safety (SCCS); REPORT_DATE=11 December 2012; VALUE_TEXT== 0.83; DOSE=Calculation of the Margin of Safety for Lip products According to the SCCS Notes of Guidance for the testing of cosmetic ingredients and their safety evaluation (SCCS/1416/11) the daily exposure to lipstick/lipproducts is 0.9 mg/kg/d.; EFFECT=nt when comparing the human NOAEL with the exposure levels for workers/consumers/general population (Reference 44, sub III). Calculation of the Margin of Safety for Lip products According to the SCCS Notes of Guidance for the testing of cosmetic ingredients and their safety evaluation (SCCS/1416/11) the daily exposure to lipstick/lipproducts is 0.9 mg/kg/d. Exposure dose (0.9 x 25%) 0.225 mg/kg bw/day. No Observed Adverse Effect Level NOAEL (oral, human)* 0.83 mg/kg bw/d Margin of Safety NOAEL/ED** = 3.7 * The NOAEL for ZnO is 50 mg Zn2+/day = 50/60= 0.83 mg /kg bw per day (Reference 44, sub III) ** Since route to route extrapolation is not needed, the (external) NOAEL is compared to the (external) exposure dose It is expected that the exposure to lipstick/lip products that contain high SPF factors (eg ZnO nanomaterial) is less than the exposure to ‘regular’ lipstick/lip products. Typically, these products are used only in specific time frames, e.g. during outdoor holidays. Therefore 0.9 mg/kg bw/d is considered a conservati; CITATION=(Reference 44, sub III); CITATION_NUMBERS=[44]; REFERENCE=(Reference 44, sub III); DETAILS_JSON={"cas_number":"1314-13-2","citation":"(Reference 44, sub III)","dose":"Calculation of the Margin of Safety for Lip products According to the SCCS Notes of Guidance for the testing of cosmetic ingredients and their safety evaluation (SCCS/1416/11) the daily exposure to lipstick/lipproducts is 0.9 mg/kg/d.","duration":"","effect":"nt when comparing the human NOAEL with the exposure levels for workers/consumers/general population (Reference 44, sub III). Calculation of the Margin of Safety for Lip products According to the SCCS Notes of Guidance for the testing of cosmetic ingredients and their safety evaluation (SCCS/1416/11) the daily exposure to lipstick/lipproducts is 0.9 mg/kg/d. Exposure dose (0.9 x 25%) 0.225 mg/kg bw/day. No Observed Adverse Effect Level NOAEL (oral, human)* 0.83 mg/kg bw/d Margin of Safety NOAEL/ED** = 3.7 * The NOAEL for ZnO is 50 mg Zn2+/day = 50/60= 0.83 mg /kg bw per day (Reference 44, sub III) ** Since route to route extrapolation is not needed, the (external) NOAEL is compared to the (external) exposure dose It is expected that the exposure to lipstick/lip products that contain high SPF factors (eg ZnO nanomaterial) is less than the exposure to ‘regular’ lipstick/lip products. Typically, these products are used only in specific time frames, e.g. during outdoor holidays. Therefore 0.9 mg/kg bw/d is considered a conservati","endpoint":"","ingredient":"codes.................................... 9","loael_value":"","noael_unit":"mg /kg bw","noael_value":"= 0.83","page":90,"route":"oral","species":"human","study_id":"sccs_o_103_noael_021"}
UnifiedCodex:SCCS_SHADOW:beta.noael_studies - =0.83 mg /kg bw human oral - - SOURCE_SUBDIR=sccs_o_103; REPORT_TITLE=OPINION ON Zinc oxide (nano form) COLIPA S 76; OPINION_NUMBER=SCCS/1489/12; COMMITTEE=Scientific Committee on Consumer Safety (SCCS); REPORT_DATE=11 December 2012; VALUE_TEXT== 0.83; DOSE=afety for Lip products According to the SCCS Notes of Guidance for the testing of cosmetic ingredients and their safety evaluation (SCCS/1416/11) the daily exposure to lipstick/lipproducts is 0.9 mg/kg/d.; EFFECT=afety for Lip products According to the SCCS Notes of Guidance for the testing of cosmetic ingredients and their safety evaluation (SCCS/1416/11) the daily exposure to lipstick/lipproducts is 0.9 mg/kg/d. Exposure dose (0.9 x 25%) 0.225 mg/kg bw/day. No Observed Adverse Effect Level NOAEL (oral, human)* 0.83 mg/kg bw/d Margin of Safety NOAEL/ED** = 3.7 * The NOAEL for ZnO is 50 mg Zn2+/day = 50/60= 0.83 mg /kg bw per day (Reference 44, sub III) ** Since route to route extrapolation is not needed, the (external) NOAEL is compared to the (external) exposure dose It is expected that the exposure to lipstick/lip products that contain high SPF factors (eg ZnO nanomaterial) is less than the exposure to ‘regular’ lipstick/lip products. Typically, these products are used only in specific time frames, e.g. during outdoor holidays. Therefore 0.9 mg/kg bw/d is considered a conservative value. The calculation of the exposure via lip products to ZnO nanoparticles assuming Zn2+ uptake results in a MoS of 3.7 (with a minimal MOS of 1 requi; CITATION=(Reference 44, sub III); CITATION_NUMBERS=[44]; REFERENCE=(Reference 44, sub III); DETAILS_JSON={"cas_number":"1314-13-2","citation":"(Reference 44, sub III)","dose":"afety for Lip products According to the SCCS Notes of Guidance for the testing of cosmetic ingredients and their safety evaluation (SCCS/1416/11) the daily exposure to lipstick/lipproducts is 0.9 mg/kg/d.","duration":"","effect":"afety for Lip products According to the SCCS Notes of Guidance for the testing of cosmetic ingredients and their safety evaluation (SCCS/1416/11) the daily exposure to lipstick/lipproducts is 0.9 mg/kg/d. Exposure dose (0.9 x 25%) 0.225 mg/kg bw/day. No Observed Adverse Effect Level NOAEL (oral, human)* 0.83 mg/kg bw/d Margin of Safety NOAEL/ED** = 3.7 * The NOAEL for ZnO is 50 mg Zn2+/day = 50/60= 0.83 mg /kg bw per day (Reference 44, sub III) ** Since route to route extrapolation is not needed, the (external) NOAEL is compared to the (external) exposure dose It is expected that the exposure to lipstick/lip products that contain high SPF factors (eg ZnO nanomaterial) is less than the exposure to ‘regular’ lipstick/lip products. Typically, these products are used only in specific time frames, e.g. during outdoor holidays. Therefore 0.9 mg/kg bw/d is considered a conservative value. The calculation of the exposure via lip products to ZnO nanoparticles assuming Zn2+ uptake results in a MoS of 3.7 (with a minimal MOS of 1 requi","endpoint":"","ingredient":"codes.................................... 9","loael_value":"","noael_unit":"mg /kg bw","noael_value":"= 0.83","page":90,"route":"oral","species":"human","study_id":"sccs_o_103_noael_022"}
UnifiedCodex:SCCS_SHADOW:beta.noael_studies - 50 - mouse oral - - SOURCE_SUBDIR=sccs_o_103; REPORT_TITLE=OPINION ON Zinc oxide (nano form) COLIPA S 76; OPINION_NUMBER=SCCS/1489/12; COMMITTEE=Scientific Committee on Consumer Safety (SCCS); REPORT_DATE=11 December 2012; VALUE_TEXT=unclear:ure In one exploratory study in mice, systemic availability of Zn was indicated after a single oral exposure. However, no differences weren observed between ZnO administered as nanoscale or microscale particles. It is likely that absorbed Zn in the GI-tract was in the dissolved ionic form. In view of the data provided, oral exposure of nano-ZnO via applications of nano-ZnO as a cosmetic ingredient in sunscreens should be considered to be of a similar risk to micron-sized ZnO as previously evaluated in the RAR. The NOAEL for oral intake of ZnO is 50 mg /bw day (Reference 44, sub III). The oral exposure to ZnO nanoparticles as cosmetic ingredient in sunscreens is limited to accidental ingestion of small fractions of lip products and sun protection products and can be considered to be low. Inhalation exposure Upon inhalation of ZnO nanoparticles, serious local effects in the lung were observed. Even if this may be due to the solubilized Zn ions, the effects are a direct result of the exposure to the ZnO nanoparticles. Therefore, th; DOSE=However, no differences weren observed between ZnO administered as nanoscale or microscale particles.; EFFECT=ure In one exploratory study in mice, systemic availability of Zn was indicated after a single oral exposure. However, no differences weren observed between ZnO administered as nanoscale or microscale particles. It is likely that absorbed Zn in the GI-tract was in the dissolved ionic form. In view of the data provided, oral exposure of nano-ZnO via applications of nano-ZnO as a cosmetic ingredient in sunscreens should be considered to be of a similar risk to micron-sized ZnO as previously evaluated in the RAR. The NOAEL for oral intake of ZnO is 50 mg /bw day (Reference 44, sub III). The oral exposure to ZnO nanoparticles as cosmetic ingredient in sunscreens is limited to accidental ingestion of small fractions of lip products and sun protection products and can be considered to be low. Inhalation exposure Upon inhalation of ZnO nanoparticles, serious local effects in the lung were observed. Even if this may be due to the solubilized Zn ions, the effects are a direct result of the exposure to the ZnO nanoparticles. Therefore, th; CITATION=(Reference 44, sub III); CITATION_NUMBERS=[44]; REFERENCE=(Reference 44, sub III); DETAILS_JSON={"cas_number":"1314-13-2","citation":"(Reference 44, sub III)","dose":"However, no differences weren observed between ZnO administered as nanoscale or microscale particles.","duration":"","effect":"ure In one exploratory study in mice, systemic availability of Zn was indicated after a single oral exposure. However, no differences weren observed between ZnO administered as nanoscale or microscale particles. It is likely that absorbed Zn in the GI-tract was in the dissolved ionic form. In view of the data provided, oral exposure of nano-ZnO via applications of nano-ZnO as a cosmetic ingredient in sunscreens should be considered to be of a similar risk to micron-sized ZnO as previously evaluated in the RAR. The NOAEL for oral intake of ZnO is 50 mg /bw day (Reference 44, sub III). The oral exposure to ZnO nanoparticles as cosmetic ingredient in sunscreens is limited to accidental ingestion of small fractions of lip products and sun protection products and can be considered to be low. Inhalation exposure Upon inhalation of ZnO nanoparticles, serious local effects in the lung were observed. Even if this may be due to the solubilized Zn ions, the effects are a direct result of the exposure to the ZnO nanoparticles. Therefore, th","endpoint":"","ingredient":"codes.................................... 9","loael_value":"","noael_unit":"","noael_value":"unclear:ure In one exploratory study in mice, systemic availability of Zn was indicated after a single oral exposure. However, no differences weren observed between ZnO administered as nanoscale or microscale particles. It is likely that absorbed Zn in the GI-tract was in the dissolved ionic form. In view of the data provided, oral exposure of nano-ZnO via applications of nano-ZnO as a cosmetic ingredient in sunscreens should be considered to be of a similar risk to micron-sized ZnO as previously evaluated in the RAR. The NOAEL for oral intake of ZnO is 50 mg /bw day (Reference 44, sub III). The oral exposure to ZnO nanoparticles as cosmetic ingredient in sunscreens is limited to accidental ingestion of small fractions of lip products and sun protection products and can be considered to be low. Inhalation exposure Upon inhalation of ZnO nanoparticles, serious local effects in the lung were observed. Even if this may be due to the solubilized Zn ions, the effects are a direct result of the exposure to the ZnO nanoparticles. Therefore, th","page":96,"route":"oral","species":"mouse","study_id":"sccs_o_103_noael_023"}
UnifiedCodex:SCCS_SHADOW:beta.noael_studies - 90 - - inhalation 90 days - SOURCE_SUBDIR=sccs_o_137; REPORT_TITLE=ADDENDUM to the OPINION SCCS/1489/12 on Zinc oxide (nano form) COLIPA S76; OPINION_NUMBER=SCCS/1518/13; COMMITTEE=Scientific Committee on Consumer Safety (SCCS); REPORT_DATE=22 April 2014; VALUE_TEXT=unclear:upporting the rapid elimination. In the study four animals were found dead or killed moribund, the cause of death being in two animals a purulent and necrotizing inflammation of the urogenital organs, in one animal due to a pronounced malignant lymphoma, and in one animal due to unknown cause. These observations were not treatment related. Conclusions The study authors concluded that transient local effects on the respiratory tract were only observed in the highest dose group for this 90 days inhalation study. A NOAEL of 1.5 g/m³ can be identified for the test item Z-COTE® HP1. Under the conditions of this test no persistent toxicity was found and all lesions were found to be recovered within the 28 day post exposure period. SCCS comments The file received for the study report was not signed by the study director and/or scientists involved. The report was supposedly to be published by the end of 2012, however, it was not found on Cefic website (June 2013). Size distributions of both nano- and micron-sized ZnO particles used; DOSE=Conclusions The study authors concluded that transient local effects on the respiratory tract were only observed in the highest dose group for this 90 days inhalation study.; EFFECT=upporting the rapid elimination. In the study four animals were found dead or killed moribund, the cause of death being in two animals a purulent and necrotizing inflammation of the urogenital organs, in one animal due to a pronounced malignant lymphoma, and in one animal due to unknown cause. These observations were not treatment related. Conclusions The study authors concluded that transient local effects on the respiratory tract were only observed in the highest dose group for this 90 days inhalation study. A NOAEL of 1.5 g/m³ can be identified for the test item Z-COTE® HP1. Under the conditions of this test no persistent toxicity was found and all lesions were found to be recovered within the 28 day post exposure period. SCCS comments The file received for the study report was not signed by the study director and/or scientists involved. The report was supposedly to be published by the end of 2012, however, it was not found on Cefic website (June 2013). Size distributions of both nano- and micron-sized ZnO particles used; CITATION_NUMBERS=[]; DETAILS_JSON={"cas_number":"1314-13-2","citation":"","dose":"Conclusions The study authors concluded that transient local effects on the respiratory tract were only observed in the highest dose group for this 90 days inhalation study.","duration":"90 days","effect":"upporting the rapid elimination. In the study four animals were found dead or killed moribund, the cause of death being in two animals a purulent and necrotizing inflammation of the urogenital organs, in one animal due to a pronounced malignant lymphoma, and in one animal due to unknown cause. These observations were not treatment related. Conclusions The study authors concluded that transient local effects on the respiratory tract were only observed in the highest dose group for this 90 days inhalation study. A NOAEL of 1.5 g/m³ can be identified for the test item Z-COTE® HP1. Under the conditions of this test no persistent toxicity was found and all lesions were found to be recovered within the 28 day post exposure period. SCCS comments The file received for the study report was not signed by the study director and/or scientists involved. The report was supposedly to be published by the end of 2012, however, it was not found on Cefic website (June 2013). Size distributions of both nano- and micron-sized ZnO particles used","endpoint":"","ingredient":"s, toys, textiles,","loael_value":"","noael_unit":"","noael_value":"unclear:upporting the rapid elimination. In the study four animals were found dead or killed moribund, the cause of death being in two animals a purulent and necrotizing inflammation of the urogenital organs, in one animal due to a pronounced malignant lymphoma, and in one animal due to unknown cause. These observations were not treatment related. Conclusions The study authors concluded that transient local effects on the respiratory tract were only observed in the highest dose group for this 90 days inhalation study. A NOAEL of 1.5 g/m³ can be identified for the test item Z-COTE® HP1. Under the conditions of this test no persistent toxicity was found and all lesions were found to be recovered within the 28 day post exposure period. SCCS comments The file received for the study report was not signed by the study director and/or scientists involved. The report was supposedly to be published by the end of 2012, however, it was not found on Cefic website (June 2013). Size distributions of both nano- and micron-sized ZnO particles used","page":12,"route":"inhalation","species":"","study_id":"sccs_o_137_noael_001"}
UnifiedCodex:SCCS_SHADOW:beta.noael_studies - 1518 - - - - - SOURCE_SUBDIR=sccs_o_137; REPORT_TITLE=ADDENDUM to the OPINION SCCS/1489/12 on Zinc oxide (nano form) COLIPA S76; OPINION_NUMBER=SCCS/1518/13; COMMITTEE=Scientific Committee on Consumer Safety (SCCS); REPORT_DATE=22 April 2014; VALUE_TEXT=unclear:SCCS/1518/13 Revision of the addendum to the opinion on zinc oxide (nano form) ___________________________________________________________________________________________ 13 animals were used. Some explanation might have given insight to how and why this was done. Statistical difference in total protein in BALF between high dose group Z-COTE® HP1 with controls not mentioned (high dose group 112.2 ± 8.7 vs control 79.6 ± 9.2 total protein). The NOAEL derived by the study authors is based on both observations in BAL and lung histopathology occurring at the high dose group and not in mid dose group of 1.5 mg/m3. However, the SCCS concludes on a NOAEL of 0.3 mg/ m3 in view of the ongoing activation of lung macrophages and lung draining lymph nodes. 4. CONCLUSION The SCCS concludes that ZnO nanomaterials with the following characteristics can be considered similar to the ZnO nanomaterials as evaluated in opinion SCCS/1489/12 and thus pose no or limited risk for; DOSE=Statistical difference in total protein in BALF between high dose group Z-COTE® HP1 with controls not mentioned (high dose group 112.2 ± 8.7 vs control 79.6 ± 9.2 total protein).; EFFECT=SCCS/1518/13 Revision of the addendum to the opinion on zinc oxide (nano form) ___________________________________________________________________________________________ 13 animals were used. Some explanation might have given insight to how and why this was done. Statistical difference in total protein in BALF between high dose group Z-COTE® HP1 with controls not mentioned (high dose group 112.2 ± 8.7 vs control 79.6 ± 9.2 total protein). The NOAEL derived by the study authors is based on both observations in BAL and lung histopathology occurring at the high dose group and not in mid dose group of 1.5 mg/m3. However, the SCCS concludes on a NOAEL of 0.3 mg/ m3 in view of the ongoing activation of lung macrophages and lung draining lymph nodes. 4. CONCLUSION The SCCS concludes that ZnO nanomaterials with the following characteristics can be considered similar to the ZnO nanomaterials as evaluated in opinion SCCS/1489/12 and thus pose no or limited risk for; CITATION_NUMBERS=[]; DETAILS_JSON={"cas_number":"1314-13-2","citation":"","dose":"Statistical difference in total protein in BALF between high dose group Z-COTE® HP1 with controls not mentioned (high dose group 112.2 ± 8.7 vs control 79.6 ± 9.2 total protein).","duration":"","effect":"SCCS/1518/13 Revision of the addendum to the opinion on zinc oxide (nano form) ___________________________________________________________________________________________ 13 animals were used. Some explanation might have given insight to how and why this was done. Statistical difference in total protein in BALF between high dose group Z-COTE® HP1 with controls not mentioned (high dose group 112.2 ± 8.7 vs control 79.6 ± 9.2 total protein). The NOAEL derived by the study authors is based on both observations in BAL and lung histopathology occurring at the high dose group and not in mid dose group of 1.5 mg/m3. However, the SCCS concludes on a NOAEL of 0.3 mg/ m3 in view of the ongoing activation of lung macrophages and lung draining lymph nodes. 4. CONCLUSION The SCCS concludes that ZnO nanomaterials with the following characteristics can be considered similar to the ZnO nanomaterials as evaluated in opinion SCCS/1489/12 and thus pose no or limited risk for","endpoint":"","ingredient":"s, toys, textiles,","loael_value":"","noael_unit":"","noael_value":"unclear:SCCS/1518/13 Revision of the addendum to the opinion on zinc oxide (nano form) ___________________________________________________________________________________________ 13 animals were used. Some explanation might have given insight to how and why this was done. Statistical difference in total protein in BALF between high dose group Z-COTE® HP1 with controls not mentioned (high dose group 112.2 ± 8.7 vs control 79.6 ± 9.2 total protein). The NOAEL derived by the study authors is based on both observations in BAL and lung histopathology occurring at the high dose group and not in mid dose group of 1.5 mg/m3. However, the SCCS concludes on a NOAEL of 0.3 mg/ m3 in view of the ongoing activation of lung macrophages and lung draining lymph nodes. 4. CONCLUSION The SCCS concludes that ZnO nanomaterials with the following characteristics can be considered similar to the ZnO nanomaterials as evaluated in opinion SCCS/1489/12 and thus pose no or limited risk for","page":13,"route":"","species":"","study_id":"sccs_o_137_noael_002"}
UnifiedCodex:SCCS_SHADOW:beta.noael_studies - 96 % - - - - SOURCE_SUBDIR=sccs_o_137; REPORT_TITLE=ADDENDUM to the OPINION SCCS/1489/12 on Zinc oxide (nano form) COLIPA S76; OPINION_NUMBER=SCCS/1518/13; COMMITTEE=Scientific Committee on Consumer Safety (SCCS); REPORT_DATE=22 April 2014; VALUE_TEXT=96; DOSE=Statistical difference in total protein in BALF between high dose group Z-COTE® HP1 with controls not mentioned (high dose group 112.2 ± 8.7 vs control 79.6 ± 9.2 total protein).; EFFECT=______________________________________ 13 animals were used. Some explanation might have given insight to how and why this was done. Statistical difference in total protein in BALF between high dose group Z-COTE® HP1 with controls not mentioned (high dose group 112.2 ± 8.7 vs control 79.6 ± 9.2 total protein). The NOAEL derived by the study authors is based on both observations in BAL and lung histopathology occurring at the high dose group and not in mid dose group of 1.5 mg/m3. However, the SCCS concludes on a NOAEL of 0.3 mg/ m3 in view of the ongoing activation of lung macrophages and lung draining lymph nodes. 4. CONCLUSION The SCCS concludes that ZnO nanomaterials with the following characteristics can be considered similar to the ZnO nanomaterials as evaluated in opinion SCCS/1489/12 and thus pose no or limited risk for use on the skin as UV filter in sunscreen formulations: 1. ZnO nanoparticles of purity ≥96%, with wurtzite crystalline structure and physical appearance as clusters that are rod-like, star-like and/or; CITATION_NUMBERS=[]; DETAILS_JSON={"cas_number":"1314-13-2","citation":"","dose":"Statistical difference in total protein in BALF between high dose group Z-COTE® HP1 with controls not mentioned (high dose group 112.2 ± 8.7 vs control 79.6 ± 9.2 total protein).","duration":"","effect":"______________________________________ 13 animals were used. Some explanation might have given insight to how and why this was done. Statistical difference in total protein in BALF between high dose group Z-COTE® HP1 with controls not mentioned (high dose group 112.2 ± 8.7 vs control 79.6 ± 9.2 total protein). The NOAEL derived by the study authors is based on both observations in BAL and lung histopathology occurring at the high dose group and not in mid dose group of 1.5 mg/m3. However, the SCCS concludes on a NOAEL of 0.3 mg/ m3 in view of the ongoing activation of lung macrophages and lung draining lymph nodes. 4. CONCLUSION The SCCS concludes that ZnO nanomaterials with the following characteristics can be considered similar to the ZnO nanomaterials as evaluated in opinion SCCS/1489/12 and thus pose no or limited risk for use on the skin as UV filter in sunscreen formulations: 1. ZnO nanoparticles of purity ≥96%, with wurtzite crystalline structure and physical appearance as clusters that are rod-like, star-like and/or","endpoint":"","ingredient":"s, toys, textiles,","loael_value":"","noael_unit":"%","noael_value":"96","page":13,"route":"","species":"","study_id":"sccs_o_137_noael_003"}
UnifiedCodex:SCCS_SHADOW:beta.noael_studies - 4 - - inhalation 90 days - SOURCE_SUBDIR=sccs_o_137; REPORT_TITLE=ADDENDUM to the OPINION SCCS/1489/12 on Zinc oxide (nano form) COLIPA S76; OPINION_NUMBER=SCCS/1518/13; COMMITTEE=Scientific Committee on Consumer Safety (SCCS); REPORT_DATE=22 April 2014; VALUE_TEXT=unclear:. Other cosmetic ingredients can be used as coatings as long as they are demonstrated to the SCCS to be safe and do not affect the particle properties related to behaviour and/or effects, compared to the nanomaterials covered in the current opinion. 4. ZnO nanoparticles that have a comparable solubility to that reported in the dossier, i.e. below 50 mg/L (approximately the maximum solubility of the ZnO nanomaterials for which data are provided in the dossier). The submitted 90 days inhalation study resulted in a NOAEL of 0.3 mg/m3. However these new data do not address the concerns relating to the lung exposure and the potential manifestation of harmful effects. 5. MINORITY OPINION / 6. REFERENCES /; EFFECT=. Other cosmetic ingredients can be used as coatings as long as they are demonstrated to the SCCS to be safe and do not affect the particle properties related to behaviour and/or effects, compared to the nanomaterials covered in the current opinion. 4. ZnO nanoparticles that have a comparable solubility to that reported in the dossier, i.e. below 50 mg/L (approximately the maximum solubility of the ZnO nanomaterials for which data are provided in the dossier). The submitted 90 days inhalation study resulted in a NOAEL of 0.3 mg/m3. However these new data do not address the concerns relating to the lung exposure and the potential manifestation of harmful effects. 5. MINORITY OPINION / 6. REFERENCES /; CITATION_NUMBERS=[]; DETAILS_JSON={"cas_number":"1314-13-2","citation":"","dose":"","duration":"90 days","effect":". Other cosmetic ingredients can be used as coatings as long as they are demonstrated to the SCCS to be safe and do not affect the particle properties related to behaviour and/or effects, compared to the nanomaterials covered in the current opinion. 4. ZnO nanoparticles that have a comparable solubility to that reported in the dossier, i.e. below 50 mg/L (approximately the maximum solubility of the ZnO nanomaterials for which data are provided in the dossier). The submitted 90 days inhalation study resulted in a NOAEL of 0.3 mg/m3. However these new data do not address the concerns relating to the lung exposure and the potential manifestation of harmful effects. 5. MINORITY OPINION / 6. REFERENCES /","endpoint":"","ingredient":"s, toys, textiles,","loael_value":"","noael_unit":"","noael_value":"unclear:. Other cosmetic ingredients can be used as coatings as long as they are demonstrated to the SCCS to be safe and do not affect the particle properties related to behaviour and/or effects, compared to the nanomaterials covered in the current opinion. 4. ZnO nanoparticles that have a comparable solubility to that reported in the dossier, i.e. below 50 mg/L (approximately the maximum solubility of the ZnO nanomaterials for which data are provided in the dossier). The submitted 90 days inhalation study resulted in a NOAEL of 0.3 mg/m3. However these new data do not address the concerns relating to the lung exposure and the potential manifestation of harmful effects. 5. MINORITY OPINION / 6. REFERENCES /","page":13,"route":"inhalation","species":"","study_id":"sccs_o_137_noael_004"}
UnifiedCodex:SCCS_SHADOW:beta.noael_studies repeated dose toxicity 1 mg/kg bw rat intravenous - repeated dose toxicity SOURCE_SUBDIR=sccs_o_103; REPORT_TITLE=OPINION ON Zinc oxide (nano form) COLIPA S 76; OPINION_NUMBER=SCCS/1489/12; COMMITTEE=Scientific Committee on Consumer Safety (SCCS); REPORT_DATE=11 December 2012; VALUE_TEXT=1; DOSE=In view of the indications for liver damage, a repeated dose toxicity study would have provided better information on potential toxicity.; EFFECT=toxic reactions were not observed. In view of the indications for liver damage, a repeated dose toxicity study would have provided better information on potential toxicity. In conclusion, after intravenous administration obtaining an internal dose of 5 mg/kg bw alterations in clinical pathology were observed that were indicative of liver damage. The liver damage appeared to be transient as similar alterations were not observed at four weeks after the single administration. Based on this study, the SCCS considers a NOAEL of 1 mg/kg bw for acute toxicity of ZnO in rats after intravenous administration. Additional studies submitted Additional information was included in the dossier on ZnO commercially obtained from Sigma-Aldrich and not related to the ZnO presented in the dossier. (References: 85, 94, 119); CITATION=(References: 85, 94, 119); CITATION_NUMBERS=[85,94,119]; REFERENCE=(References: 85, 94, 119); DETAILS_JSON={"cas_number":"1314-13-2","citation":"(References: 85, 94, 119)","dose":"In view of the indications for liver damage, a repeated dose toxicity study would have provided better information on potential toxicity.","duration":"","effect":"toxic reactions were not observed. In view of the indications for liver damage, a repeated dose toxicity study would have provided better information on potential toxicity. In conclusion, after intravenous administration obtaining an internal dose of 5 mg/kg bw alterations in clinical pathology were observed that were indicative of liver damage. The liver damage appeared to be transient as similar alterations were not observed at four weeks after the single administration. Based on this study, the SCCS considers a NOAEL of 1 mg/kg bw for acute toxicity of ZnO in rats after intravenous administration. Additional studies submitted Additional information was included in the dossier on ZnO commercially obtained from Sigma-Aldrich and not related to the ZnO presented in the dossier. (References: 85, 94, 119)","endpoint":"repeated dose toxicity","ingredient":"codes.................................... 9","loael_value":"","noael_unit":"mg/kg bw","noael_value":"1","page":86,"route":"intravenous","species":"rat","study_id":"sccs_o_103_noael_003"}
UnifiedCodex:SCCS_SHADOW:beta.noael_studies repeated dose toxicity 2 % human oral 18 days repeated dose toxicity SOURCE_SUBDIR=sccs_o_103; REPORT_TITLE=OPINION ON Zinc oxide (nano form) COLIPA S 76; OPINION_NUMBER=SCCS/1489/12; COMMITTEE=Scientific Committee on Consumer Safety (SCCS); REPORT_DATE=11 December 2012; VALUE_TEXT=2; DOSE=An NOAEL of 50 mg Zn2+/day was derived from a 10-week oral study with human volunteers and was used as a starting point for the risk characterization for repeated dose toxicity.; EFFECT=nc or zinc compounds is therefore chosen to be 2%. Based on the physical appearance, for dust exposure to zinc or zinc compounds a 10-fold lower default value of 0.2% is chosen in the risk assessment. For sunscreen containing 10% zinc oxide the following exposure assessment was performed: By an application of 9 g sunscreen/event, 3 events/day during 18 days/year the exposure will be 1,332 mg sunscreen/day, being 107 mg Zn2+/day. Assuming a dermal absorption of 2% the uptake is estimated to be 2.14 mg Zn2+/ day. An NOAEL of 50 mg Zn2+/day was derived from a 10-week oral study with human volunteers and was used as a starting point for the risk characterization for repeated dose toxicity. This NOAEL of 50 mg Zn2+/day results in an internal NOAEL of 10 mg Zn2+/day by correction for oral absorption (20%; worst case, because of the homeostasis the relative absorption will be smaller by excess of Zn2+-intake). Given that this study was with women (the most sensitive population in zinc supplementation studies), and that in women clinical; CITATION_NUMBERS=[]; DETAILS_JSON={"cas_number":"1314-13-2","citation":"","dose":"An NOAEL of 50 mg Zn2+/day was derived from a 10-week oral study with human volunteers and was used as a starting point for the risk characterization for repeated dose toxicity.","duration":"18 days","effect":"nc or zinc compounds is therefore chosen to be 2%. Based on the physical appearance, for dust exposure to zinc or zinc compounds a 10-fold lower default value of 0.2% is chosen in the risk assessment. For sunscreen containing 10% zinc oxide the following exposure assessment was performed: By an application of 9 g sunscreen/event, 3 events/day during 18 days/year the exposure will be 1,332 mg sunscreen/day, being 107 mg Zn2+/day. Assuming a dermal absorption of 2% the uptake is estimated to be 2.14 mg Zn2+/ day. An NOAEL of 50 mg Zn2+/day was derived from a 10-week oral study with human volunteers and was used as a starting point for the risk characterization for repeated dose toxicity. This NOAEL of 50 mg Zn2+/day results in an internal NOAEL of 10 mg Zn2+/day by correction for oral absorption (20%; worst case, because of the homeostasis the relative absorption will be smaller by excess of Zn2+-intake). Given that this study was with women (the most sensitive population in zinc supplementation studies), and that in women clinical","endpoint":"repeated dose toxicity","ingredient":"codes.................................... 9","loael_value":"","noael_unit":"%","noael_value":"2","page":89,"route":"oral","species":"human","study_id":"sccs_o_103_noael_004"}
UnifiedCodex:SCCS_SHADOW:beta.noael_studies repeated dose toxicity 20 % human oral 18 days repeated dose toxicity SOURCE_SUBDIR=sccs_o_103; REPORT_TITLE=OPINION ON Zinc oxide (nano form) COLIPA S 76; OPINION_NUMBER=SCCS/1489/12; COMMITTEE=Scientific Committee on Consumer Safety (SCCS); REPORT_DATE=11 December 2012; VALUE_TEXT=20; DOSE=An NOAEL of 50 mg Zn2+/day was derived from a 10-week oral study with human volunteers and was used as a starting point for the risk characterization for repeated dose toxicity.; EFFECT=the risk assessment. For sunscreen containing 10% zinc oxide the following exposure assessment was performed: By an application of 9 g sunscreen/event, 3 events/day during 18 days/year the exposure will be 1,332 mg sunscreen/day, being 107 mg Zn2+/day. Assuming a dermal absorption of 2% the uptake is estimated to be 2.14 mg Zn2+/ day. An NOAEL of 50 mg Zn2+/day was derived from a 10-week oral study with human volunteers and was used as a starting point for the risk characterization for repeated dose toxicity. This NOAEL of 50 mg Zn2+/day results in an internal NOAEL of 10 mg Zn2+/day by correction for oral absorption (20%; worst case, because of the homeostasis the relative absorption will be smaller by excess of Zn2+-intake). Given that this study was with women (the most sensitive population in zinc supplementation studies), and that in women clinical signs begin to appear only at a dose three times this NOAEL, a minimal MOS of 1 is considered sufficient when comparing the human NOAEL with the exposure levels for workers/consum; CITATION_NUMBERS=[]; DETAILS_JSON={"cas_number":"1314-13-2","citation":"","dose":"An NOAEL of 50 mg Zn2+/day was derived from a 10-week oral study with human volunteers and was used as a starting point for the risk characterization for repeated dose toxicity.","duration":"18 days","effect":"the risk assessment. For sunscreen containing 10% zinc oxide the following exposure assessment was performed: By an application of 9 g sunscreen/event, 3 events/day during 18 days/year the exposure will be 1,332 mg sunscreen/day, being 107 mg Zn2+/day. Assuming a dermal absorption of 2% the uptake is estimated to be 2.14 mg Zn2+/ day. An NOAEL of 50 mg Zn2+/day was derived from a 10-week oral study with human volunteers and was used as a starting point for the risk characterization for repeated dose toxicity. This NOAEL of 50 mg Zn2+/day results in an internal NOAEL of 10 mg Zn2+/day by correction for oral absorption (20%; worst case, because of the homeostasis the relative absorption will be smaller by excess of Zn2+-intake). Given that this study was with women (the most sensitive population in zinc supplementation studies), and that in women clinical signs begin to appear only at a dose three times this NOAEL, a minimal MOS of 1 is considered sufficient when comparing the human NOAEL with the exposure levels for workers/consum","endpoint":"repeated dose toxicity","ingredient":"codes.................................... 9","loael_value":"","noael_unit":"%","noael_value":"20","page":89,"route":"oral","species":"human","study_id":"sccs_o_103_noael_005"}
UnifiedCodex:SCCS_SHADOW:beta.noael_studies repeated dose toxicity 20 % human oral 18 days repeated dose toxicity SOURCE_SUBDIR=sccs_o_103; REPORT_TITLE=OPINION ON Zinc oxide (nano form) COLIPA S 76; OPINION_NUMBER=SCCS/1489/12; COMMITTEE=Scientific Committee on Consumer Safety (SCCS); REPORT_DATE=11 December 2012; VALUE_TEXT=20; DOSE=An NOAEL of 50 mg Zn2+/day was derived from a 10-week oral study with human volunteers and was used as a starting point for the risk characterization for repeated dose toxicity.; EFFECT=0% zinc oxide the following exposure assessment was performed: By an application of 9 g sunscreen/event, 3 events/day during 18 days/year the exposure will be 1,332 mg sunscreen/day, being 107 mg Zn2+/day. Assuming a dermal absorption of 2% the uptake is estimated to be 2.14 mg Zn2+/ day. An NOAEL of 50 mg Zn2+/day was derived from a 10-week oral study with human volunteers and was used as a starting point for the risk characterization for repeated dose toxicity. This NOAEL of 50 mg Zn2+/day results in an internal NOAEL of 10 mg Zn2+/day by correction for oral absorption (20%; worst case, because of the homeostasis the relative absorption will be smaller by excess of Zn2+-intake). Given that this study was with women (the most sensitive population in zinc supplementation studies), and that in women clinical signs begin to appear only at a dose three times this NOAEL, a minimal MOS of 1 is considered sufficient when comparing the human NOAEL with the exposure levels for workers/consumers/general population. The MOS between this in; CITATION_NUMBERS=[]; DETAILS_JSON={"cas_number":"1314-13-2","citation":"","dose":"An NOAEL of 50 mg Zn2+/day was derived from a 10-week oral study with human volunteers and was used as a starting point for the risk characterization for repeated dose toxicity.","duration":"18 days","effect":"0% zinc oxide the following exposure assessment was performed: By an application of 9 g sunscreen/event, 3 events/day during 18 days/year the exposure will be 1,332 mg sunscreen/day, being 107 mg Zn2+/day. Assuming a dermal absorption of 2% the uptake is estimated to be 2.14 mg Zn2+/ day. An NOAEL of 50 mg Zn2+/day was derived from a 10-week oral study with human volunteers and was used as a starting point for the risk characterization for repeated dose toxicity. This NOAEL of 50 mg Zn2+/day results in an internal NOAEL of 10 mg Zn2+/day by correction for oral absorption (20%; worst case, because of the homeostasis the relative absorption will be smaller by excess of Zn2+-intake). Given that this study was with women (the most sensitive population in zinc supplementation studies), and that in women clinical signs begin to appear only at a dose three times this NOAEL, a minimal MOS of 1 is considered sufficient when comparing the human NOAEL with the exposure levels for workers/consumers/general population. The MOS between this in","endpoint":"repeated dose toxicity","ingredient":"codes.................................... 9","loael_value":"","noael_unit":"%","noael_value":"20","page":89,"route":"oral","species":"human","study_id":"sccs_o_103_noael_006"}
UnifiedCodex:SCCS_SHADOW:beta.noael_studies repeated dose toxicity 20 % human oral - repeated dose toxicity SOURCE_SUBDIR=sccs_o_103; REPORT_TITLE=OPINION ON Zinc oxide (nano form) COLIPA S 76; OPINION_NUMBER=SCCS/1489/12; COMMITTEE=Scientific Committee on Consumer Safety (SCCS); REPORT_DATE=11 December 2012; VALUE_TEXT=20; DOSE=y with human volunteers and was used as a starting point for the risk characterization for repeated dose toxicity.; EFFECT=y with human volunteers and was used as a starting point for the risk characterization for repeated dose toxicity. This NOAEL of 50 mg Zn2+/day results in an internal NOAEL of 10 mg Zn2+/day by correction for oral absorption (20%; worst case, because of the homeostasis the relative absorption will be smaller by excess of Zn2+-intake). Given that this study was with women (the most sensitive population in zinc supplementation studies), and that in women clinical signs begin to appear only at a dose three times this NOAEL, a minimal MOS of 1 is considered sufficient when comparing the human NOAEL with the exposure levels for workers/consumers/general population. The MOS between this internal NOAEL and the internal exposure as a result of exposure to sunscreen formulations is 5, which is a factor of 5 larger than the minimal MOS. The SCCS agrees with the NOAEL indicated in the RAR statement. Therefore, this information is used together with the data from the absorption study provided in the dossier and exposure assumptions from th; CITATION_NUMBERS=[]; DETAILS_JSON={"cas_number":"1314-13-2","citation":"","dose":"y with human volunteers and was used as a starting point for the risk characterization for repeated dose toxicity.","duration":"","effect":"y with human volunteers and was used as a starting point for the risk characterization for repeated dose toxicity. This NOAEL of 50 mg Zn2+/day results in an internal NOAEL of 10 mg Zn2+/day by correction for oral absorption (20%; worst case, because of the homeostasis the relative absorption will be smaller by excess of Zn2+-intake). Given that this study was with women (the most sensitive population in zinc supplementation studies), and that in women clinical signs begin to appear only at a dose three times this NOAEL, a minimal MOS of 1 is considered sufficient when comparing the human NOAEL with the exposure levels for workers/consumers/general population. The MOS between this internal NOAEL and the internal exposure as a result of exposure to sunscreen formulations is 5, which is a factor of 5 larger than the minimal MOS. The SCCS agrees with the NOAEL indicated in the RAR statement. Therefore, this information is used together with the data from the absorption study provided in the dossier and exposure assumptions from th","endpoint":"repeated dose toxicity","ingredient":"codes.................................... 9","loael_value":"","noael_unit":"%","noael_value":"20","page":89,"route":"oral","species":"human","study_id":"sccs_o_103_noael_007"}
UnifiedCodex:SCCS_SHADOW:beta.noael_studies repeated dose toxicity 20 % human oral - repeated dose toxicity SOURCE_SUBDIR=sccs_o_103; REPORT_TITLE=OPINION ON Zinc oxide (nano form) COLIPA S 76; OPINION_NUMBER=SCCS/1489/12; COMMITTEE=Scientific Committee on Consumer Safety (SCCS); REPORT_DATE=11 December 2012; VALUE_TEXT=20; DOSE=terization for repeated dose toxicity.; EFFECT=terization for repeated dose toxicity. This NOAEL of 50 mg Zn2+/day results in an internal NOAEL of 10 mg Zn2+/day by correction for oral absorption (20%; worst case, because of the homeostasis the relative absorption will be smaller by excess of Zn2+-intake). Given that this study was with women (the most sensitive population in zinc supplementation studies), and that in women clinical signs begin to appear only at a dose three times this NOAEL, a minimal MOS of 1 is considered sufficient when comparing the human NOAEL with the exposure levels for workers/consumers/general population. The MOS between this internal NOAEL and the internal exposure as a result of exposure to sunscreen formulations is 5, which is a factor of 5 larger than the minimal MOS. The SCCS agrees with the NOAEL indicated in the RAR statement. Therefore, this information is used together with the data from the absorption study provided in the dossier and exposure assumptions from the SCCS Notes of Guidance for the risk assessment of zinc oxide nanoparticles; CITATION_NUMBERS=[]; DETAILS_JSON={"cas_number":"1314-13-2","citation":"","dose":"terization for repeated dose toxicity.","duration":"","effect":"terization for repeated dose toxicity. This NOAEL of 50 mg Zn2+/day results in an internal NOAEL of 10 mg Zn2+/day by correction for oral absorption (20%; worst case, because of the homeostasis the relative absorption will be smaller by excess of Zn2+-intake). Given that this study was with women (the most sensitive population in zinc supplementation studies), and that in women clinical signs begin to appear only at a dose three times this NOAEL, a minimal MOS of 1 is considered sufficient when comparing the human NOAEL with the exposure levels for workers/consumers/general population. The MOS between this internal NOAEL and the internal exposure as a result of exposure to sunscreen formulations is 5, which is a factor of 5 larger than the minimal MOS. The SCCS agrees with the NOAEL indicated in the RAR statement. Therefore, this information is used together with the data from the absorption study provided in the dossier and exposure assumptions from the SCCS Notes of Guidance for the risk assessment of zinc oxide nanoparticles","endpoint":"repeated dose toxicity","ingredient":"codes.................................... 9","loael_value":"","noael_unit":"%","noael_value":"20","page":89,"route":"oral","species":"human","study_id":"sccs_o_103_noael_008"}
openFDA substances 4 endpoints
Source Endpoint Type Value Unit Species Route Duration Study Type Reference
openFDA substances FDA UNII substance identifier SOI2LOH54Z UNII - - - chemical {"approval_status":null,"molecular_formula":"O.Zn","source_table":"substance_identifiers_fda","substance_class":"chemical","unii_code":"SOI2LOH54Z"}
openFDA substances FDA UNII substance identifier SOI2LOH54Z UNII - - - chemical {"approval_status":null,"molecular_formula":"O.Zn","source_table":"substance_identifiers_fda","substance_class":"chemical","unii_code":"SOI2LOH54Z"}
openFDA substances FDA UNII substance identifier SOI2LOH54Z UNII - - - chemical {"approval_status":null,"molecular_formula":"O.Zn","source_table":"substance_identifiers_fda","substance_class":"chemical","unii_code":"SOI2LOH54Z"}
openFDA substances FDA UNII substance identifier SOI2LOH54Z UNII - - - chemical {"approval_status":null,"molecular_formula":"O.Zn","source_table":"substance_identifiers_fda","substance_class":"chemical","unii_code":"SOI2LOH54Z"}