NOAEL Studies Cosmetic Ingredient

Bis-(Diethylaminohydroxybenzoyl Benzoyl) Piperazine NOAEL Studies

INCI: BIS-(DIETHYLAMINOHYDROXYBENZOYL BENZOYL) PIPERAZINE

CAS: 919803-06-8

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

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SCCS Opinion 24 endpoints
Source Endpoint Type Value Unit Species Route Duration Study Type Reference
SCCS Opinion NOAEL =100 % - oral 13 week NOAEL study {"dose":"SCCS/1533/14 Revision of the Opinion on the safety of HAA299 as UV filter in sunscreen products ___________________________________________________________________________________________ 67 MoS represents the ratio between the No Observed (Adverse) Effect Level (NOEL/NOAEL) and systemic exposure dose (SED).","effect":"SCCS-rejected applicant NOAEL: SCCS/1533/14 Revision of the Opinion on the safety of HAA299 as UV filter in sunscreen products ___________________________________________________________________________________________ 67 MoS represents the ratio between the No Observed (Adverse) Effect Level (NOEL/NOAEL) and systemic exposure dose (SED). The SCCS is of the opinion that the submitted data are not appropriate for calculation of MoS. The uncorrected NOEL/NOAEL (assuming 100% absorption) of HAA299 is 1000 mg/kg bw/d based on a 13 week study with oral gavage. Two toxicokinetic studies have been performed. In a study with “large micronised” particles of d(05) = 8.33 µm the total absorption was calculated to 1.93% while the impurity content was about 8% of the test material. In another experiment with micronised","page":67,"pdf":"sccs_o_159.pdf","row_type":"noael_study","study_id":"sccs_o_159_noael_014"}
SCCS Opinion NOAEL =100 % - oral 13 week NOAEL study {"dose":"SCCS/1533/14 Revision of the Opinion on the safety of HAA299 as UV filter in sunscreen products ___________________________________________________________________________________________ 67 MoS represents the ratio between the No Observed (Adverse) Effect Level (NOEL/NOAEL) and systemic exposure dose (SED).","effect":"SCCS-rejected applicant NOAEL: SCCS/1533/14 Revision of the Opinion on the safety of HAA299 as UV filter in sunscreen products ___________________________________________________________________________________________ 67 MoS represents the ratio between the No Observed (Adverse) Effect Level (NOEL/NOAEL) and systemic exposure dose (SED). The SCCS is of the opinion that the submitted data are not appropriate for calculation of MoS. The uncorrected NOEL/NOAEL (assuming 100% absorption) of HAA299 is 1000 mg/kg bw/d based on a 13 week study with oral gavage. Two toxicokinetic studies have been performed. In a study with “large micronised” particles of d(05) = 8.33 µm the total absorption was calculated to 1.93% while the impurity content was about 8% of the test material. In another experiment with micronised","page":67,"pdf":"sccs_o_159.pdf","row_type":"noael_study","study_id":"sccs_o_159_noael_014"}
SCCS Opinion NOAEL =100 % - oral 13 week NOAEL study {"dose":"SCCS/1533/14 Revision of the Opinion on the safety of HAA299 as UV filter in sunscreen products ___________________________________________________________________________________________ 67 MoS represents the ratio between the No Observed (Adverse) Effect Level (NOEL/NOAEL) and systemic exposure dose (SED).","effect":"SCCS-rejected applicant NOAEL: SCCS/1533/14 Revision of the Opinion on the safety of HAA299 as UV filter in sunscreen products ___________________________________________________________________________________________ 67 MoS represents the ratio between the No Observed (Adverse) Effect Level (NOEL/NOAEL) and systemic exposure dose (SED). The SCCS is of the opinion that the submitted data are not appropriate for calculation of MoS. The uncorrected NOEL/NOAEL (assuming 100% absorption) of HAA299 is 1000 mg/kg bw/d based on a 13 week study with oral gavage. Two toxicokinetic studies have been performed. In a study with “large micronised” particles of d(05) = 8.33 µm the total absorption was calculated to 1.93% while the impurity content was about 8% of the test material. In another experiment with micronised","page":67,"pdf":"sccs_o_159.pdf","row_type":"noael_study","study_id":"sccs_o_159_noael_014"}
SCCS Opinion NOAEL =100 % - oral 13 week NOAEL study {"dose":"SCCS/1533/14 Revision of the Opinion on the safety of HAA299 as UV filter in sunscreen products ___________________________________________________________________________________________ 67 MoS represents the ratio between the No Observed (Adverse) Effect Level (NOEL/NOAEL) and systemic exposure dose (SED).","effect":"SCCS-rejected applicant NOAEL: SCCS/1533/14 Revision of the Opinion on the safety of HAA299 as UV filter in sunscreen products ___________________________________________________________________________________________ 67 MoS represents the ratio between the No Observed (Adverse) Effect Level (NOEL/NOAEL) and systemic exposure dose (SED). The SCCS is of the opinion that the submitted data are not appropriate for calculation of MoS. The uncorrected NOEL/NOAEL (assuming 100% absorption) of HAA299 is 1000 mg/kg bw/d based on a 13 week study with oral gavage. Two toxicokinetic studies have been performed. In a study with “large micronised” particles of d(05) = 8.33 µm the total absorption was calculated to 1.93% while the impurity content was about 8% of the test material. In another experiment with micronised","page":67,"pdf":"sccs_o_159.pdf","row_type":"noael_study","study_id":"sccs_o_159_noael_014"}
SCCS Opinion NOAEL =299 - - - 5 days repeated dose toxicity {"dose":"Summary of the delivery data Applicants’ conclusion on reproduction and developmental toxicity Based on the experimental conditions, the dose-level of 1000 mg a.i./kg/day was defined as No Observed Adverse Effect Level (NOAEL) for parental toxicity, reproductive performance (mating and fertility) and development.","effect":"artum, HAA299 (nano), i.e. micronised HAA299 in a formulation, C- 1332 there were no effects on mating, fertility, delivery, pup survival or development during 5 days of lactation. No histopathological lesions considered to be reflective of systemic toxicity including male and female reproductive organs were observed. Table 18: Summary of the delivery data Applicants’ conclusion on reproduction and developmental toxicity Based on the experimental conditions, the dose-level of 1000 mg a.i./kg/day was defined as No Observed Adverse Effect Level (NOAEL) for parental toxicity, reproductive performance (mating and fertility) and development. SCCS comment Based on the results on fertility and developmental parameters assessed in the repeated dose toxicity study (45 days) with the Reproduction/Developmental Toxicity Screening Test (3.4.4.2), 1000 mg a.i./kg/day is considered to be the NOAELrepro. For other endpoints see section 3.4.4.2. 3.4.5.2 Teratogenicity No teratogenicity data are available for HAA299 (nano). Some developmental aspects on HAA299 neat","page":42,"pdf":"sccs_o_256.pdf","row_type":"noael_study","study_id":"sccs_o_256_noael_006"}
SCCS Opinion NOAEL =299 - - - 5 days repeated dose toxicity {"dose":"Summary of the delivery data Applicants’ conclusion on reproduction and developmental toxicity Based on the experimental conditions, the dose-level of 1000 mg a.i./kg/day was defined as No Observed Adverse Effect Level (NOAEL) for parental toxicity, reproductive performance (mating and fertility) and development.","effect":"artum, HAA299 (nano), i.e. micronised HAA299 in a formulation, C- 1332 there were no effects on mating, fertility, delivery, pup survival or development during 5 days of lactation. No histopathological lesions considered to be reflective of systemic toxicity including male and female reproductive organs were observed. Table 18: Summary of the delivery data Applicants’ conclusion on reproduction and developmental toxicity Based on the experimental conditions, the dose-level of 1000 mg a.i./kg/day was defined as No Observed Adverse Effect Level (NOAEL) for parental toxicity, reproductive performance (mating and fertility) and development. SCCS comment Based on the results on fertility and developmental parameters assessed in the repeated dose toxicity study (45 days) with the Reproduction/Developmental Toxicity Screening Test (3.4.4.2), 1000 mg a.i./kg/day is considered to be the NOAELrepro. For other endpoints see section 3.4.4.2. 3.4.5.2 Teratogenicity No teratogenicity data are available for HAA299 (nano). Some developmental aspects on HAA299 neat","page":42,"pdf":"sccs_o_256.pdf","row_type":"noael_study","study_id":"sccs_o_256_noael_006"}
SCCS Opinion NOAEL =299 - - - 5 days repeated dose toxicity {"dose":"Summary of the delivery data Applicants’ conclusion on reproduction and developmental toxicity Based on the experimental conditions, the dose-level of 1000 mg a.i./kg/day was defined as No Observed Adverse Effect Level (NOAEL) for parental toxicity, reproductive performance (mating and fertility) and development.","effect":"artum, HAA299 (nano), i.e. micronised HAA299 in a formulation, C- 1332 there were no effects on mating, fertility, delivery, pup survival or development during 5 days of lactation. No histopathological lesions considered to be reflective of systemic toxicity including male and female reproductive organs were observed. Table 18: Summary of the delivery data Applicants’ conclusion on reproduction and developmental toxicity Based on the experimental conditions, the dose-level of 1000 mg a.i./kg/day was defined as No Observed Adverse Effect Level (NOAEL) for parental toxicity, reproductive performance (mating and fertility) and development. SCCS comment Based on the results on fertility and developmental parameters assessed in the repeated dose toxicity study (45 days) with the Reproduction/Developmental Toxicity Screening Test (3.4.4.2), 1000 mg a.i./kg/day is considered to be the NOAELrepro. For other endpoints see section 3.4.4.2. 3.4.5.2 Teratogenicity No teratogenicity data are available for HAA299 (nano). Some developmental aspects on HAA299 neat","page":42,"pdf":"sccs_o_256.pdf","row_type":"noael_study","study_id":"sccs_o_256_noael_006"}
SCCS Opinion NOAEL =299 - - - 5 days repeated dose toxicity {"dose":"Summary of the delivery data Applicants’ conclusion on reproduction and developmental toxicity Based on the experimental conditions, the dose-level of 1000 mg a.i./kg/day was defined as No Observed Adverse Effect Level (NOAEL) for parental toxicity, reproductive performance (mating and fertility) and development.","effect":"artum, HAA299 (nano), i.e. micronised HAA299 in a formulation, C- 1332 there were no effects on mating, fertility, delivery, pup survival or development during 5 days of lactation. No histopathological lesions considered to be reflective of systemic toxicity including male and female reproductive organs were observed. Table 18: Summary of the delivery data Applicants’ conclusion on reproduction and developmental toxicity Based on the experimental conditions, the dose-level of 1000 mg a.i./kg/day was defined as No Observed Adverse Effect Level (NOAEL) for parental toxicity, reproductive performance (mating and fertility) and development. SCCS comment Based on the results on fertility and developmental parameters assessed in the repeated dose toxicity study (45 days) with the Reproduction/Developmental Toxicity Screening Test (3.4.4.2), 1000 mg a.i./kg/day is considered to be the NOAELrepro. For other endpoints see section 3.4.4.2. 3.4.5.2 Teratogenicity No teratogenicity data are available for HAA299 (nano). Some developmental aspects on HAA299 neat","page":42,"pdf":"sccs_o_256.pdf","row_type":"noael_study","study_id":"sccs_o_256_noael_006"}
SCCS Opinion NOAEL =1000 mg/kg/day rat oral 13 weeks genotoxicity {"citation":"Ref.: 3 SCCS comment The absence of effect observed up to the highest dose may be related to the low bioavailability","dose":"SCCS/1533/14 Revision of the Opinion on the safety of HAA299 as UV filter in sunscreen products ___________________________________________________________________________________________ 33 Conclusion Under the experimental conditions of this study, the No Observed (Adverse) Effect Level (NOEL/NOAEL) of HAA299 given by oral route to rats for 13...","effect":"SCCS/1533/14 Revision of the Opinion on the safety of HAA299 as UV filter in sunscreen products ___________________________________________________________________________________________ 33 Conclusion Under the experimental conditions of this study, the No Observed (Adverse) Effect Level (NOEL/NOAEL) of HAA299 given by oral route to rats for 13 weeks at constant dose-levels can be established at 1000 mg/kg/day. Ref.: 3 SCCS comment The absence of effect observed up to the highest dose may be related to the low bioavailability. A.3.3.5.3. Chronic (> 12 months) toxicity / A.3.3.6. Mutagenicity / Genotoxicity A.3.3.6.1 Mutagenicity / Genotoxicity in vitro Bacterial Reverse Mutation Test Guideline: OECD no. 471 Species/strain: Salmonella typhimurium, TA98, TA100, TA1535, TA1537 Escherichia coli,","page":33,"pdf":"sccs_o_159.pdf","row_type":"noael_study","study_id":"sccs_o_159_noael_001"}
SCCS Opinion NOAEL =1000 mg/kg bw/day rat - developmental developmental toxicity {"citation":"Ref.: 11 SCCS comment The absence of effect observed up to the highest dose may be related to the low bioavailability","dose":"There were no skeletal malformations in fetuses from the groups treated with the test item.","effect":"nt. There were no skeletal malformations in fetuses from the groups treated with the test item. All skeletal variations recorded in the treated groups were observed at incidences similar to the controls and were not related to treatment. Conclusion HAA299 was well tolerated by the dams, with no adverse effects at any dose-level. Fetal examination resulted in no treatment-related malformations or variations at any dose-level. Under the experimental conditions of this study, the No Observed (Adverse) Effect Level (NOEL/NOAEL) for both the maternal toxicity and the developmental toxicity was identified at 1000 mg/kg bw/day. Ref.: 11 SCCS comment The absence of effect observed up to the highest dose may be related to the low bioavailability. A.3.3.9. Toxicokinetics Large, micronised particles Guideline: OECD no. 417 Species/strain: Male HanRcc:WIST (SPF): Wistar rats about 7 weeks old, approx 200 g Group size: Group 1: 4 males, for mass balance Group 2: 9 males, for blood kinetics Test substance: FAT 75’808/B Batch: VTM05B10","page":39,"pdf":"sccs_o_159.pdf","row_type":"noael_study","study_id":"sccs_o_159_noael_002"}
SCCS Opinion NOAEL =1000 mg/kg bw/d rat oral - repeated dose toxicity {"dose":"The calculation of margin of safety (MoS) is not justified given the low dermal penetration when applied on human skin, and in consideration of the low observed systemic toxicity (NOEL/NOAEL for oral administration of HAA299 to rats is 1000 mg/kg bw/d).","effect":"otosensitisation / B.3.3.10.2. Phototoxicity / photomutagenicity / photoclastogenicity / B.3.3.11. Human data / B.3.3.12. Special investigations / C.3.3.1. Safety evaluation (including calculation of the MoS) Safety evaluation of HAA299 batches containing non-nano particles can be performed on the basis of the submitted dossier: The calculation of margin of safety (MoS) is not justified given the low dermal penetration when applied on human skin, and in consideration of the low observed systemic toxicity (NOEL/NOAEL for oral administration of HAA299 to rats is 1000 mg/kg bw/d). Therefore no concern is raised with regard to systemic toxicity. Safety evaluation of HAA299 batches containing nano particles cannot be performed on the basis of the submitted dossier, because the dossier included only acute oral toxicity, acute inhalation toxicity, repeated dose toxicity and 2 in vivo mutagenicity tests. C.3.3.2. Discussion As a complete dossier of HAA299 nano-batches for safety evaluation, according to SCCS Notes of Guidan","page":63,"pdf":"sccs_o_159.pdf","row_type":"noael_study","study_id":"sccs_o_159_noael_007"}
SCCS Opinion NOAEL =1000 mg/kg rat - 45 days repeated dose toxicity {"citation":"Ref: CIT F-Evreux, 20 March 2009 SCCS comment In this repeated dose toxicity study (45 days), one male rat, in the highest dose, was found to show some deviation of the control paramete","dose":"Based on the experimental conditions of this study, the highest dose-level tested (1000 mg a.i./kg/day) was determined as No Observed Adverse Effect Level (NOAEL).","effect":"_______________________ ___________________________________________________________________________________________ 41 not elicit signs of systemic toxicity. Non-adverse clinical signs of hypersalivation, reflux at dosing and loud breathing were sporadically observed at 250 and/or 1000 mg a.i./kg/day. No histopathological lesions considered to be reflective of systemic toxicity were observed. Based on the experimental conditions of this study, the highest dose-level tested (1000 mg a.i./kg/day) was determined as No Observed Adverse Effect Level (NOAEL). Ref: CIT F-Evreux, 20 March 2009 SCCS comment In this repeated dose toxicity study (45 days), one male rat, in the highest dose, was found to show some deviation of the control parameters indicative for the presence of an inflammatory reaction (increase in WBC and PMN) while other blood values were within normal ranges. However, the histopathology did not show any organ with a severe inflammation that might explain the WBC, PMN and RTC increases in the blood. Overall, the SCCS considers 1000 mg/kg as th","page":41,"pdf":"sccs_o_256.pdf","row_type":"noael_study","study_id":"sccs_o_256_noael_002"}
SCCS Opinion NOAEL =1000 mg/kg/day rat oral 13 weeks genotoxicity {"citation":"Ref.: 3 SCCS comment The absence of effect observed up to the highest dose may be related to the low bioavailability","dose":"SCCS/1533/14 Revision of the Opinion on the safety of HAA299 as UV filter in sunscreen products ___________________________________________________________________________________________ 33 Conclusion Under the experimental conditions of this study, the No Observed (Adverse) Effect Level (NOEL/NOAEL) of HAA299 given by oral route to rats for 13...","effect":"SCCS/1533/14 Revision of the Opinion on the safety of HAA299 as UV filter in sunscreen products ___________________________________________________________________________________________ 33 Conclusion Under the experimental conditions of this study, the No Observed (Adverse) Effect Level (NOEL/NOAEL) of HAA299 given by oral route to rats for 13 weeks at constant dose-levels can be established at 1000 mg/kg/day. Ref.: 3 SCCS comment The absence of effect observed up to the highest dose may be related to the low bioavailability. A.3.3.5.3. Chronic (> 12 months) toxicity / A.3.3.6. Mutagenicity / Genotoxicity A.3.3.6.1 Mutagenicity / Genotoxicity in vitro Bacterial Reverse Mutation Test Guideline: OECD no. 471 Species/strain: Salmonella typhimurium, TA98, TA100, TA1535, TA1537 Escherichia coli,","page":33,"pdf":"sccs_o_159.pdf","row_type":"noael_study","study_id":"sccs_o_159_noael_001"}
SCCS Opinion NOAEL =1000 mg/kg bw/day rat - developmental developmental toxicity {"citation":"Ref.: 11 SCCS comment The absence of effect observed up to the highest dose may be related to the low bioavailability","dose":"There were no skeletal malformations in fetuses from the groups treated with the test item.","effect":"nt. There were no skeletal malformations in fetuses from the groups treated with the test item. All skeletal variations recorded in the treated groups were observed at incidences similar to the controls and were not related to treatment. Conclusion HAA299 was well tolerated by the dams, with no adverse effects at any dose-level. Fetal examination resulted in no treatment-related malformations or variations at any dose-level. Under the experimental conditions of this study, the No Observed (Adverse) Effect Level (NOEL/NOAEL) for both the maternal toxicity and the developmental toxicity was identified at 1000 mg/kg bw/day. Ref.: 11 SCCS comment The absence of effect observed up to the highest dose may be related to the low bioavailability. A.3.3.9. Toxicokinetics Large, micronised particles Guideline: OECD no. 417 Species/strain: Male HanRcc:WIST (SPF): Wistar rats about 7 weeks old, approx 200 g Group size: Group 1: 4 males, for mass balance Group 2: 9 males, for blood kinetics Test substance: FAT 75’808/B Batch: VTM05B10","page":39,"pdf":"sccs_o_159.pdf","row_type":"noael_study","study_id":"sccs_o_159_noael_002"}
SCCS Opinion NOAEL =1000 mg/kg bw/d rat oral - repeated dose toxicity {"dose":"The calculation of margin of safety (MoS) is not justified given the low dermal penetration when applied on human skin, and in consideration of the low observed systemic toxicity (NOEL/NOAEL for oral administration of HAA299 to rats is 1000 mg/kg bw/d).","effect":"otosensitisation / B.3.3.10.2. Phototoxicity / photomutagenicity / photoclastogenicity / B.3.3.11. Human data / B.3.3.12. Special investigations / C.3.3.1. Safety evaluation (including calculation of the MoS) Safety evaluation of HAA299 batches containing non-nano particles can be performed on the basis of the submitted dossier: The calculation of margin of safety (MoS) is not justified given the low dermal penetration when applied on human skin, and in consideration of the low observed systemic toxicity (NOEL/NOAEL for oral administration of HAA299 to rats is 1000 mg/kg bw/d). Therefore no concern is raised with regard to systemic toxicity. Safety evaluation of HAA299 batches containing nano particles cannot be performed on the basis of the submitted dossier, because the dossier included only acute oral toxicity, acute inhalation toxicity, repeated dose toxicity and 2 in vivo mutagenicity tests. C.3.3.2. Discussion As a complete dossier of HAA299 nano-batches for safety evaluation, according to SCCS Notes of Guidan","page":63,"pdf":"sccs_o_159.pdf","row_type":"noael_study","study_id":"sccs_o_159_noael_007"}
SCCS Opinion NOAEL =1000 mg/kg/day rat oral 13 weeks genotoxicity {"citation":"Ref.: 3 SCCS comment The absence of effect observed up to the highest dose may be related to the low bioavailability","dose":"SCCS/1533/14 Revision of the Opinion on the safety of HAA299 as UV filter in sunscreen products ___________________________________________________________________________________________ 33 Conclusion Under the experimental conditions of this study, the No Observed (Adverse) Effect Level (NOEL/NOAEL) of HAA299 given by oral route to rats for 13...","effect":"SCCS/1533/14 Revision of the Opinion on the safety of HAA299 as UV filter in sunscreen products ___________________________________________________________________________________________ 33 Conclusion Under the experimental conditions of this study, the No Observed (Adverse) Effect Level (NOEL/NOAEL) of HAA299 given by oral route to rats for 13 weeks at constant dose-levels can be established at 1000 mg/kg/day. Ref.: 3 SCCS comment The absence of effect observed up to the highest dose may be related to the low bioavailability. A.3.3.5.3. Chronic (> 12 months) toxicity / A.3.3.6. Mutagenicity / Genotoxicity A.3.3.6.1 Mutagenicity / Genotoxicity in vitro Bacterial Reverse Mutation Test Guideline: OECD no. 471 Species/strain: Salmonella typhimurium, TA98, TA100, TA1535, TA1537 Escherichia coli,","page":33,"pdf":"sccs_o_159.pdf","row_type":"noael_study","study_id":"sccs_o_159_noael_001"}
SCCS Opinion NOAEL =1000 mg/kg bw/day rat - developmental developmental toxicity {"citation":"Ref.: 11 SCCS comment The absence of effect observed up to the highest dose may be related to the low bioavailability","dose":"There were no skeletal malformations in fetuses from the groups treated with the test item.","effect":"nt. There were no skeletal malformations in fetuses from the groups treated with the test item. All skeletal variations recorded in the treated groups were observed at incidences similar to the controls and were not related to treatment. Conclusion HAA299 was well tolerated by the dams, with no adverse effects at any dose-level. Fetal examination resulted in no treatment-related malformations or variations at any dose-level. Under the experimental conditions of this study, the No Observed (Adverse) Effect Level (NOEL/NOAEL) for both the maternal toxicity and the developmental toxicity was identified at 1000 mg/kg bw/day. Ref.: 11 SCCS comment The absence of effect observed up to the highest dose may be related to the low bioavailability. A.3.3.9. Toxicokinetics Large, micronised particles Guideline: OECD no. 417 Species/strain: Male HanRcc:WIST (SPF): Wistar rats about 7 weeks old, approx 200 g Group size: Group 1: 4 males, for mass balance Group 2: 9 males, for blood kinetics Test substance: FAT 75’808/B Batch: VTM05B10","page":39,"pdf":"sccs_o_159.pdf","row_type":"noael_study","study_id":"sccs_o_159_noael_002"}
SCCS Opinion NOAEL =1000 mg/kg bw/d rat oral - repeated dose toxicity {"dose":"The calculation of margin of safety (MoS) is not justified given the low dermal penetration when applied on human skin, and in consideration of the low observed systemic toxicity (NOEL/NOAEL for oral administration of HAA299 to rats is 1000 mg/kg bw/d).","effect":"otosensitisation / B.3.3.10.2. Phototoxicity / photomutagenicity / photoclastogenicity / B.3.3.11. Human data / B.3.3.12. Special investigations / C.3.3.1. Safety evaluation (including calculation of the MoS) Safety evaluation of HAA299 batches containing non-nano particles can be performed on the basis of the submitted dossier: The calculation of margin of safety (MoS) is not justified given the low dermal penetration when applied on human skin, and in consideration of the low observed systemic toxicity (NOEL/NOAEL for oral administration of HAA299 to rats is 1000 mg/kg bw/d). Therefore no concern is raised with regard to systemic toxicity. Safety evaluation of HAA299 batches containing nano particles cannot be performed on the basis of the submitted dossier, because the dossier included only acute oral toxicity, acute inhalation toxicity, repeated dose toxicity and 2 in vivo mutagenicity tests. C.3.3.2. Discussion As a complete dossier of HAA299 nano-batches for safety evaluation, according to SCCS Notes of Guidan","page":63,"pdf":"sccs_o_159.pdf","row_type":"noael_study","study_id":"sccs_o_159_noael_007"}
SCCS Opinion NOAEL =1000 mg/kg rat - 45 days repeated dose toxicity {"citation":"Ref: CIT F-Evreux, 20 March 2009 SCCS comment In this repeated dose toxicity study (45 days), one male rat, in the highest dose, was found to show some deviation of the control paramete","dose":"Based on the experimental conditions of this study, the highest dose-level tested (1000 mg a.i./kg/day) was determined as No Observed Adverse Effect Level (NOAEL).","effect":"_______________________ ___________________________________________________________________________________________ 41 not elicit signs of systemic toxicity. Non-adverse clinical signs of hypersalivation, reflux at dosing and loud breathing were sporadically observed at 250 and/or 1000 mg a.i./kg/day. No histopathological lesions considered to be reflective of systemic toxicity were observed. Based on the experimental conditions of this study, the highest dose-level tested (1000 mg a.i./kg/day) was determined as No Observed Adverse Effect Level (NOAEL). Ref: CIT F-Evreux, 20 March 2009 SCCS comment In this repeated dose toxicity study (45 days), one male rat, in the highest dose, was found to show some deviation of the control parameters indicative for the presence of an inflammatory reaction (increase in WBC and PMN) while other blood values were within normal ranges. However, the histopathology did not show any organ with a severe inflammation that might explain the WBC, PMN and RTC increases in the blood. Overall, the SCCS considers 1000 mg/kg as th","page":41,"pdf":"sccs_o_256.pdf","row_type":"noael_study","study_id":"sccs_o_256_noael_002"}
SCCS Opinion NOAEL =1000 mg/kg rat - 45 days repeated dose toxicity {"citation":"Ref: CIT F-Evreux, 20 March 2009 SCCS comment In this repeated dose toxicity study (45 days), one male rat, in the highest dose, was found to show some deviation of the control paramete","dose":"Based on the experimental conditions of this study, the highest dose-level tested (1000 mg a.i./kg/day) was determined as No Observed Adverse Effect Level (NOAEL).","effect":"_______________________ ___________________________________________________________________________________________ 41 not elicit signs of systemic toxicity. Non-adverse clinical signs of hypersalivation, reflux at dosing and loud breathing were sporadically observed at 250 and/or 1000 mg a.i./kg/day. No histopathological lesions considered to be reflective of systemic toxicity were observed. Based on the experimental conditions of this study, the highest dose-level tested (1000 mg a.i./kg/day) was determined as No Observed Adverse Effect Level (NOAEL). Ref: CIT F-Evreux, 20 March 2009 SCCS comment In this repeated dose toxicity study (45 days), one male rat, in the highest dose, was found to show some deviation of the control parameters indicative for the presence of an inflammatory reaction (increase in WBC and PMN) while other blood values were within normal ranges. However, the histopathology did not show any organ with a severe inflammation that might explain the WBC, PMN and RTC increases in the blood. Overall, the SCCS considers 1000 mg/kg as th","page":41,"pdf":"sccs_o_256.pdf","row_type":"noael_study","study_id":"sccs_o_256_noael_002"}
SCCS Opinion NOAEL =1000 mg/kg/day rat oral 13 weeks genotoxicity {"citation":"Ref.: 3 SCCS comment The absence of effect observed up to the highest dose may be related to the low bioavailability","dose":"SCCS/1533/14 Revision of the Opinion on the safety of HAA299 as UV filter in sunscreen products ___________________________________________________________________________________________ 33 Conclusion Under the experimental conditions of this study, the No Observed (Adverse) Effect Level (NOEL/NOAEL) of HAA299 given by oral route to rats for 13...","effect":"SCCS/1533/14 Revision of the Opinion on the safety of HAA299 as UV filter in sunscreen products ___________________________________________________________________________________________ 33 Conclusion Under the experimental conditions of this study, the No Observed (Adverse) Effect Level (NOEL/NOAEL) of HAA299 given by oral route to rats for 13 weeks at constant dose-levels can be established at 1000 mg/kg/day. Ref.: 3 SCCS comment The absence of effect observed up to the highest dose may be related to the low bioavailability. A.3.3.5.3. Chronic (> 12 months) toxicity / A.3.3.6. Mutagenicity / Genotoxicity A.3.3.6.1 Mutagenicity / Genotoxicity in vitro Bacterial Reverse Mutation Test Guideline: OECD no. 471 Species/strain: Salmonella typhimurium, TA98, TA100, TA1535, TA1537 Escherichia coli,","page":33,"pdf":"sccs_o_159.pdf","row_type":"noael_study","study_id":"sccs_o_159_noael_001"}
SCCS Opinion NOAEL =1000 mg/kg bw/day rat - developmental developmental toxicity {"citation":"Ref.: 11 SCCS comment The absence of effect observed up to the highest dose may be related to the low bioavailability","dose":"There were no skeletal malformations in fetuses from the groups treated with the test item.","effect":"nt. There were no skeletal malformations in fetuses from the groups treated with the test item. All skeletal variations recorded in the treated groups were observed at incidences similar to the controls and were not related to treatment. Conclusion HAA299 was well tolerated by the dams, with no adverse effects at any dose-level. Fetal examination resulted in no treatment-related malformations or variations at any dose-level. Under the experimental conditions of this study, the No Observed (Adverse) Effect Level (NOEL/NOAEL) for both the maternal toxicity and the developmental toxicity was identified at 1000 mg/kg bw/day. Ref.: 11 SCCS comment The absence of effect observed up to the highest dose may be related to the low bioavailability. A.3.3.9. Toxicokinetics Large, micronised particles Guideline: OECD no. 417 Species/strain: Male HanRcc:WIST (SPF): Wistar rats about 7 weeks old, approx 200 g Group size: Group 1: 4 males, for mass balance Group 2: 9 males, for blood kinetics Test substance: FAT 75’808/B Batch: VTM05B10","page":39,"pdf":"sccs_o_159.pdf","row_type":"noael_study","study_id":"sccs_o_159_noael_002"}
SCCS Opinion NOAEL =1000 mg/kg bw/d rat oral - repeated dose toxicity {"dose":"The calculation of margin of safety (MoS) is not justified given the low dermal penetration when applied on human skin, and in consideration of the low observed systemic toxicity (NOEL/NOAEL for oral administration of HAA299 to rats is 1000 mg/kg bw/d).","effect":"otosensitisation / B.3.3.10.2. Phototoxicity / photomutagenicity / photoclastogenicity / B.3.3.11. Human data / B.3.3.12. Special investigations / C.3.3.1. Safety evaluation (including calculation of the MoS) Safety evaluation of HAA299 batches containing non-nano particles can be performed on the basis of the submitted dossier: The calculation of margin of safety (MoS) is not justified given the low dermal penetration when applied on human skin, and in consideration of the low observed systemic toxicity (NOEL/NOAEL for oral administration of HAA299 to rats is 1000 mg/kg bw/d). Therefore no concern is raised with regard to systemic toxicity. Safety evaluation of HAA299 batches containing nano particles cannot be performed on the basis of the submitted dossier, because the dossier included only acute oral toxicity, acute inhalation toxicity, repeated dose toxicity and 2 in vivo mutagenicity tests. C.3.3.2. Discussion As a complete dossier of HAA299 nano-batches for safety evaluation, according to SCCS Notes of Guidan","page":63,"pdf":"sccs_o_159.pdf","row_type":"noael_study","study_id":"sccs_o_159_noael_007"}
SCCS Opinion NOAEL =1000 mg/kg rat - 45 days repeated dose toxicity {"citation":"Ref: CIT F-Evreux, 20 March 2009 SCCS comment In this repeated dose toxicity study (45 days), one male rat, in the highest dose, was found to show some deviation of the control paramete","dose":"Based on the experimental conditions of this study, the highest dose-level tested (1000 mg a.i./kg/day) was determined as No Observed Adverse Effect Level (NOAEL).","effect":"_______________________ ___________________________________________________________________________________________ 41 not elicit signs of systemic toxicity. Non-adverse clinical signs of hypersalivation, reflux at dosing and loud breathing were sporadically observed at 250 and/or 1000 mg a.i./kg/day. No histopathological lesions considered to be reflective of systemic toxicity were observed. Based on the experimental conditions of this study, the highest dose-level tested (1000 mg a.i./kg/day) was determined as No Observed Adverse Effect Level (NOAEL). Ref: CIT F-Evreux, 20 March 2009 SCCS comment In this repeated dose toxicity study (45 days), one male rat, in the highest dose, was found to show some deviation of the control parameters indicative for the presence of an inflammatory reaction (increase in WBC and PMN) while other blood values were within normal ranges. However, the histopathology did not show any organ with a severe inflammation that might explain the WBC, PMN and RTC increases in the blood. Overall, the SCCS considers 1000 mg/kg as th","page":41,"pdf":"sccs_o_256.pdf","row_type":"noael_study","study_id":"sccs_o_256_noael_002"}
Regulatory source 28 endpoints
Source Endpoint Type Value Unit Species Route Duration Study Type Reference
Regulatory source - 100 % - oral 13 week - SOURCE_SUBDIR=sccs_o_159; REPORT_TITLE=OPINION ON 2-(4-(2-(4-Diethylamino-2-hydroxy-benzoyl)-benzoyl)- piperazine-1-carbonyl)-phenyl)- (4-diethylamino-2- hydroxyphenyl)-methanone (HAA299) as UV filter in sunscreen products; OPINION_NUMBER=SCCS/1533/14; COMMITTEE=Scientific Committee on Consumer Safety (SCCS); REPORT_DATE=23 September 2014; VALUE_TEXT=100; DOSE=SCCS/1533/14 Revision of the Opinion on the safety of HAA299 as UV filter in sunscreen products ___________________________________________________________________________________________ 67 MoS represents the ratio between the No Observed (Adverse) Effect Level (NOEL/NOAEL) and systemic exposure dose (SED).; EFFECT=SCCS-rejected applicant NOAEL: SCCS/1533/14 Revision of the Opinion on the safety of HAA299 as UV filter in sunscreen products ___________________________________________________________________________________________ 67 MoS represents the ratio between the No Observed (Adverse) Effect Level (NOEL/NOAEL) and systemic exposure dose (SED). The SCCS is of the opinion that the submitted data are not appropriate for calculation of MoS. The uncorrected NOEL/NOAEL (assuming 100% absorption) of HAA299 is 1000 mg/kg bw/d based on a 13 week study with oral gavage. Two toxicokinetic studies have been performed. In a study with “large micronised” particles of d(05) = 8.33 µm the total absorption was calculated to 1.93% while the impurity content was about 8% of the test material. In another experiment with micronised; CITATION_NUMBERS=[]; DETAILS_JSON={"cas_number":"919803-06-8","citation":"","dose":"SCCS/1533/14 Revision of the Opinion on the safety of HAA299 as UV filter in sunscreen products ___________________________________________________________________________________________ 67 MoS represents the ratio between the No Observed (Adverse) Effect Level (NOEL/NOAEL) and systemic exposure dose (SED).","duration":"13 week","effect":"SCCS-rejected applicant NOAEL: SCCS/1533/14 Revision of the Opinion on the safety of HAA299 as UV filter in sunscreen products ___________________________________________________________________________________________ 67 MoS represents the ratio between the No Observed (Adverse) Effect Level (NOEL/NOAEL) and systemic exposure dose (SED). The SCCS is of the opinion that the submitted data are not appropriate for calculation of MoS. The uncorrected NOEL/NOAEL (assuming 100% absorption) of HAA299 is 1000 mg/kg bw/d based on a 13 week study with oral gavage. Two toxicokinetic studies have been performed. In a study with “large micronised” particles of d(05) = 8.33 µm the total absorption was calculated to 1.93% while the impurity content was about 8% of the test material. In another experiment with micronised","endpoint":"","ingredient":"HAA299","loael_value":"","noael_unit":"%","noael_value":"100","page":67,"route":"oral","species":"","study_id":"sccs_o_159_noael_014"}
Regulatory source developmental toxicity 1000 mg/kg bw/day rat - developmental developmental toxicity SOURCE_SUBDIR=sccs_o_159; REPORT_TITLE=OPINION ON 2-(4-(2-(4-Diethylamino-2-hydroxy-benzoyl)-benzoyl)- piperazine-1-carbonyl)-phenyl)- (4-diethylamino-2- hydroxyphenyl)-methanone (HAA299) as UV filter in sunscreen products; OPINION_NUMBER=SCCS/1533/14; COMMITTEE=Scientific Committee on Consumer Safety (SCCS); REPORT_DATE=23 September 2014; VALUE_TEXT=1000; DOSE=There were no skeletal malformations in fetuses from the groups treated with the test item.; EFFECT=nt. There were no skeletal malformations in fetuses from the groups treated with the test item. All skeletal variations recorded in the treated groups were observed at incidences similar to the controls and were not related to treatment. Conclusion HAA299 was well tolerated by the dams, with no adverse effects at any dose-level. Fetal examination resulted in no treatment-related malformations or variations at any dose-level. Under the experimental conditions of this study, the No Observed (Adverse) Effect Level (NOEL/NOAEL) for both the maternal toxicity and the developmental toxicity was identified at 1000 mg/kg bw/day. Ref.: 11 SCCS comment The absence of effect observed up to the highest dose may be related to the low bioavailability. A.3.3.9. Toxicokinetics Large, micronised particles Guideline: OECD no. 417 Species/strain: Male HanRcc:WIST (SPF): Wistar rats about 7 weeks old, approx 200 g Group size: Group 1: 4 males, for mass balance Group 2: 9 males, for blood kinetics Test substance: FAT 75’808/B Batch: VTM05B10; CITATION=Ref.: 11 SCCS comment The absence of effect observed up to the highest dose may be related to the low bioavailability; CITATION_NUMBERS=[11]; REFERENCE=Ref.: 11 SCCS comment The absence of effect observed up to the highest dose may be related to the low bioavailability; DETAILS_JSON={"cas_number":"919803-06-8","citation":"Ref.: 11 SCCS comment The absence of effect observed up to the highest dose may be related to the low bioavailability","dose":"There were no skeletal malformations in fetuses from the groups treated with the test item.","duration":"developmental","effect":"nt. There were no skeletal malformations in fetuses from the groups treated with the test item. All skeletal variations recorded in the treated groups were observed at incidences similar to the controls and were not related to treatment. Conclusion HAA299 was well tolerated by the dams, with no adverse effects at any dose-level. Fetal examination resulted in no treatment-related malformations or variations at any dose-level. Under the experimental conditions of this study, the No Observed (Adverse) Effect Level (NOEL/NOAEL) for both the maternal toxicity and the developmental toxicity was identified at 1000 mg/kg bw/day. Ref.: 11 SCCS comment The absence of effect observed up to the highest dose may be related to the low bioavailability. A.3.3.9. Toxicokinetics Large, micronised particles Guideline: OECD no. 417 Species/strain: Male HanRcc:WIST (SPF): Wistar rats about 7 weeks old, approx 200 g Group size: Group 1: 4 males, for mass balance Group 2: 9 males, for blood kinetics Test substance: FAT 75’808/B Batch: VTM05B10","endpoint":"developmental toxicity","ingredient":"HAA299","loael_value":"","noael_unit":"mg/kg bw/day","noael_value":"1000","page":39,"route":"","species":"rat","study_id":"sccs_o_159_noael_002"}
Regulatory source developmental toxicity 1000 mg/kg bw/day rat - developmental developmental toxicity SOURCE_SUBDIR=sccs_o_159; REPORT_TITLE=OPINION ON 2-(4-(2-(4-Diethylamino-2-hydroxy-benzoyl)-benzoyl)- piperazine-1-carbonyl)-phenyl)- (4-diethylamino-2- hydroxyphenyl)-methanone (HAA299) as UV filter in sunscreen products; OPINION_NUMBER=SCCS/1533/14; COMMITTEE=Scientific Committee on Consumer Safety (SCCS); REPORT_DATE=23 September 2014; VALUE_TEXT=1000; DOSE=There were no skeletal malformations in fetuses from the groups treated with the test item.; EFFECT=There were no skeletal malformations in fetuses from the groups treated with the test item. All skeletal variations recorded in the treated groups were observed at incidences similar to the controls and were not related to treatment. Conclusion HAA299 was well tolerated by the dams, with no adverse effects at any dose-level. Fetal examination resulted in no treatment-related malformations or variations at any dose-level. Under the experimental conditions of this study, the No Observed (Adverse) Effect Level (NOEL/NOAEL) for both the maternal toxicity and the developmental toxicity was identified at 1000 mg/kg bw/day. Ref.: 11 SCCS comment The absence of effect observed up to the highest dose may be related to the low bioavailability. A.3.3.9. Toxicokinetics Large, micronised particles Guideline: OECD no. 417 Species/strain: Male HanRcc:WIST (SPF): Wistar rats about 7 weeks old, approx 200 g Group size: Group 1: 4 males, for mass balance Group 2: 9 males, for blood kinetics Test substance: FAT 75’808/B Batch: VTM05B10 Test; CITATION=Ref.: 11 SCCS comment The absence of effect observed up to the highest dose may be related to the low bioavailability; CITATION_NUMBERS=[11]; REFERENCE=Ref.: 11 SCCS comment The absence of effect observed up to the highest dose may be related to the low bioavailability; DETAILS_JSON={"cas_number":"919803-06-8","citation":"Ref.: 11 SCCS comment The absence of effect observed up to the highest dose may be related to the low bioavailability","dose":"There were no skeletal malformations in fetuses from the groups treated with the test item.","duration":"developmental","effect":"There were no skeletal malformations in fetuses from the groups treated with the test item. All skeletal variations recorded in the treated groups were observed at incidences similar to the controls and were not related to treatment. Conclusion HAA299 was well tolerated by the dams, with no adverse effects at any dose-level. Fetal examination resulted in no treatment-related malformations or variations at any dose-level. Under the experimental conditions of this study, the No Observed (Adverse) Effect Level (NOEL/NOAEL) for both the maternal toxicity and the developmental toxicity was identified at 1000 mg/kg bw/day. Ref.: 11 SCCS comment The absence of effect observed up to the highest dose may be related to the low bioavailability. A.3.3.9. Toxicokinetics Large, micronised particles Guideline: OECD no. 417 Species/strain: Male HanRcc:WIST (SPF): Wistar rats about 7 weeks old, approx 200 g Group size: Group 1: 4 males, for mass balance Group 2: 9 males, for blood kinetics Test substance: FAT 75’808/B Batch: VTM05B10 Test","endpoint":"developmental toxicity","ingredient":"HAA299","loael_value":"","noael_unit":"mg/kg bw/day","noael_value":"1000","page":39,"route":"","species":"rat","study_id":"sccs_o_159_noael_003"}
Regulatory source genotoxicity 1000 mg/kg/day rat oral 13 weeks genotoxicity SOURCE_SUBDIR=sccs_o_159; REPORT_TITLE=OPINION ON 2-(4-(2-(4-Diethylamino-2-hydroxy-benzoyl)-benzoyl)- piperazine-1-carbonyl)-phenyl)- (4-diethylamino-2- hydroxyphenyl)-methanone (HAA299) as UV filter in sunscreen products; OPINION_NUMBER=SCCS/1533/14; COMMITTEE=Scientific Committee on Consumer Safety (SCCS); REPORT_DATE=23 September 2014; VALUE_TEXT=1000; DOSE=SCCS/1533/14 Revision of the Opinion on the safety of HAA299 as UV filter in sunscreen products ___________________________________________________________________________________________ 33 Conclusion Under the experimental conditions of this study, the No Observed (Adverse) Effect Level (NOEL/NOAEL) of HAA299 given by oral route to rats for 13...; EFFECT=SCCS/1533/14 Revision of the Opinion on the safety of HAA299 as UV filter in sunscreen products ___________________________________________________________________________________________ 33 Conclusion Under the experimental conditions of this study, the No Observed (Adverse) Effect Level (NOEL/NOAEL) of HAA299 given by oral route to rats for 13 weeks at constant dose-levels can be established at 1000 mg/kg/day. Ref.: 3 SCCS comment The absence of effect observed up to the highest dose may be related to the low bioavailability. A.3.3.5.3. Chronic (> 12 months) toxicity / A.3.3.6. Mutagenicity / Genotoxicity A.3.3.6.1 Mutagenicity / Genotoxicity in vitro Bacterial Reverse Mutation Test Guideline: OECD no. 471 Species/strain: Salmonella typhimurium, TA98, TA100, TA1535, TA1537 Escherichia coli,; CITATION=Ref.: 3 SCCS comment The absence of effect observed up to the highest dose may be related to the low bioavailability; CITATION_NUMBERS=[3]; REFERENCE=Ref.: 3 SCCS comment The absence of effect observed up to the highest dose may be related to the low bioavailability; DETAILS_JSON={"cas_number":"919803-06-8","citation":"Ref.: 3 SCCS comment The absence of effect observed up to the highest dose may be related to the low bioavailability","dose":"SCCS/1533/14 Revision of the Opinion on the safety of HAA299 as UV filter in sunscreen products ___________________________________________________________________________________________ 33 Conclusion Under the experimental conditions of this study, the No Observed (Adverse) Effect Level (NOEL/NOAEL) of HAA299 given by oral route to rats for 13...","duration":"13 weeks","effect":"SCCS/1533/14 Revision of the Opinion on the safety of HAA299 as UV filter in sunscreen products ___________________________________________________________________________________________ 33 Conclusion Under the experimental conditions of this study, the No Observed (Adverse) Effect Level (NOEL/NOAEL) of HAA299 given by oral route to rats for 13 weeks at constant dose-levels can be established at 1000 mg/kg/day. Ref.: 3 SCCS comment The absence of effect observed up to the highest dose may be related to the low bioavailability. A.3.3.5.3. Chronic (> 12 months) toxicity / A.3.3.6. Mutagenicity / Genotoxicity A.3.3.6.1 Mutagenicity / Genotoxicity in vitro Bacterial Reverse Mutation Test Guideline: OECD no. 471 Species/strain: Salmonella typhimurium, TA98, TA100, TA1535, TA1537 Escherichia coli,","endpoint":"genotoxicity","ingredient":"HAA299","loael_value":"","noael_unit":"mg/kg/day","noael_value":"1000","page":33,"route":"oral","species":"rat","study_id":"sccs_o_159_noael_001"}
Regulatory source genotoxicity 1000 mg/kg bw/d rat oral - genotoxicity SOURCE_SUBDIR=sccs_o_159; REPORT_TITLE=OPINION ON 2-(4-(2-(4-Diethylamino-2-hydroxy-benzoyl)-benzoyl)- piperazine-1-carbonyl)-phenyl)- (4-diethylamino-2- hydroxyphenyl)-methanone (HAA299) as UV filter in sunscreen products; OPINION_NUMBER=SCCS/1533/14; COMMITTEE=Scientific Committee on Consumer Safety (SCCS); REPORT_DATE=23 September 2014; VALUE_TEXT=1000; DOSE=The calculation of margin of safety (MoS) is not justified given the low dermal penetration when applied on human skin, and in consideration of the low observed systemic toxicity (NOEL/NOAEL for oral administration of HAA299 to rats is 1000 mg/kg bw/d).; EFFECT=ts in a concentration up to maximum 10.0 % is safe for the consumers taken into account the scientific data provided? This opinion covers the safety evaluation of HAA299 (micronised or non-micronised), which is not composed of nano particles. The opinion does not cover the safety evaluation of HAA299 which is composed of nano particles. The calculation of margin of safety (MoS) is not justified given the low dermal penetration when applied on human skin, and in consideration of the low observed systemic toxicity (NOEL/NOAEL for oral administration of HAA299 to rats is 1000 mg/kg bw/d). The SCCS is of the opinion that the use of non-nano HAA299 (micronised or non- micronised, with median particle size distribution around 134 nm or larger, as measured by FOQELS) at a concentration up to 10% as an UV-filter in cosmetic products, does not pose a risk of systemic toxicity in humans. The results of genotoxicity testing were negative in vitro as well as in vivo but exposure of target cells was not proven. However, in light of the lo; CITATION_NUMBERS=[]; DETAILS_JSON={"cas_number":"919803-06-8","citation":"","dose":"The calculation of margin of safety (MoS) is not justified given the low dermal penetration when applied on human skin, and in consideration of the low observed systemic toxicity (NOEL/NOAEL for oral administration of HAA299 to rats is 1000 mg/kg bw/d).","duration":"","effect":"ts in a concentration up to maximum 10.0 % is safe for the consumers taken into account the scientific data provided? This opinion covers the safety evaluation of HAA299 (micronised or non-micronised), which is not composed of nano particles. The opinion does not cover the safety evaluation of HAA299 which is composed of nano particles. The calculation of margin of safety (MoS) is not justified given the low dermal penetration when applied on human skin, and in consideration of the low observed systemic toxicity (NOEL/NOAEL for oral administration of HAA299 to rats is 1000 mg/kg bw/d). The SCCS is of the opinion that the use of non-nano HAA299 (micronised or non- micronised, with median particle size distribution around 134 nm or larger, as measured by FOQELS) at a concentration up to 10% as an UV-filter in cosmetic products, does not pose a risk of systemic toxicity in humans. The results of genotoxicity testing were negative in vitro as well as in vivo but exposure of target cells was not proven. However, in light of the lo","endpoint":"genotoxicity","ingredient":"HAA299","loael_value":"","noael_unit":"mg/kg bw/d","noael_value":"1000","page":67,"route":"oral","species":"rat","study_id":"sccs_o_159_noael_015"}
Regulatory source genotoxicity 1000 mg/kg bw/d rat oral - genotoxicity SOURCE_SUBDIR=sccs_o_159; REPORT_TITLE=OPINION ON 2-(4-(2-(4-Diethylamino-2-hydroxy-benzoyl)-benzoyl)- piperazine-1-carbonyl)-phenyl)- (4-diethylamino-2- hydroxyphenyl)-methanone (HAA299) as UV filter in sunscreen products; OPINION_NUMBER=SCCS/1533/14; COMMITTEE=Scientific Committee on Consumer Safety (SCCS); REPORT_DATE=23 September 2014; VALUE_TEXT=1000; DOSE=The calculation of margin of safety (MoS) is not justified given the low dermal penetration when applied on human skin, and in consideration of the low observed systemic toxicity (NOEL/NOAEL for oral administration of HAA299 to rats is 1000 mg/kg bw/d).; EFFECT=a concentration up to maximum 10.0 % is safe for the consumers taken into account the scientific data provided? This opinion covers the safety evaluation of HAA299 (micronised or non-micronised), which is not composed of nano particles. The opinion does not cover the safety evaluation of HAA299 which is composed of nano particles. The calculation of margin of safety (MoS) is not justified given the low dermal penetration when applied on human skin, and in consideration of the low observed systemic toxicity (NOEL/NOAEL for oral administration of HAA299 to rats is 1000 mg/kg bw/d). The SCCS is of the opinion that the use of non-nano HAA299 (micronised or non- micronised, with median particle size distribution around 134 nm or larger, as measured by FOQELS) at a concentration up to 10% as an UV-filter in cosmetic products, does not pose a risk of systemic toxicity in humans. The results of genotoxicity testing were negative in vitro as well as in vivo but exposure of target cells was not proven. However, in light of the low bioa; CITATION_NUMBERS=[]; DETAILS_JSON={"cas_number":"919803-06-8","citation":"","dose":"The calculation of margin of safety (MoS) is not justified given the low dermal penetration when applied on human skin, and in consideration of the low observed systemic toxicity (NOEL/NOAEL for oral administration of HAA299 to rats is 1000 mg/kg bw/d).","duration":"","effect":"a concentration up to maximum 10.0 % is safe for the consumers taken into account the scientific data provided? This opinion covers the safety evaluation of HAA299 (micronised or non-micronised), which is not composed of nano particles. The opinion does not cover the safety evaluation of HAA299 which is composed of nano particles. The calculation of margin of safety (MoS) is not justified given the low dermal penetration when applied on human skin, and in consideration of the low observed systemic toxicity (NOEL/NOAEL for oral administration of HAA299 to rats is 1000 mg/kg bw/d). The SCCS is of the opinion that the use of non-nano HAA299 (micronised or non- micronised, with median particle size distribution around 134 nm or larger, as measured by FOQELS) at a concentration up to 10% as an UV-filter in cosmetic products, does not pose a risk of systemic toxicity in humans. The results of genotoxicity testing were negative in vitro as well as in vivo but exposure of target cells was not proven. However, in light of the low bioa","endpoint":"genotoxicity","ingredient":"HAA299","loael_value":"","noael_unit":"mg/kg bw/d","noael_value":"1000","page":67,"route":"oral","species":"rat","study_id":"sccs_o_159_noael_016"}
Regulatory source irritation 1000 mg/kg bw/day rat oral - irritation SOURCE_SUBDIR=sccs_o_256; REPORT_TITLE=Final Opinion Scientific Committee on Consumer Safety SCCS OPINION ON HAA299 (nano); OPINION_NUMBER=SCCS/1634/21; COMMITTEE=Scientific Committee on Consumer Safety (SCCS); REPORT_DATE=27 October 2021; VALUE_TEXT=1000; DOSE=3.4.9 Human data / 3.4.10 Special investigations / 3.5 SAFETY EVALUATION (INCLUDING CALCULATION OF THE MOS) The calculation of margin of safety (MoS) is not justified given the low dermal penetration when applied on human skin, and in consideration of the quite high NOAEL for oral administration of HAA299(nano) to rats at 1000 mg/kg bw/day.; EFFECT=tential of HAA299 (nano) unlikely. 3.4.8.1 Phototoxicity/photo-irritation and photosensitisation 3.4.8.2 Photomutagenicity/photoclastogenicity / SCCS comment No photomutagenicity or photoclastogenicity tests are available for HAA299 (nano). 3.4.9 Human data / 3.4.10 Special investigations / 3.5 SAFETY EVALUATION (INCLUDING CALCULATION OF THE MOS) The calculation of margin of safety (MoS) is not justified given the low dermal penetration when applied on human skin, and in consideration of the quite high NOAEL for oral administration of HAA299(nano) to rats at 1000 mg/kg bw/day. Therefore, no concern is raised with regard to systemic toxicity. 3.6 DISCUSSION PHYSICOCHEMICAL PROPERTIES The identity of impurities that are present in batches of HAA299 (nano) must also be reported in terms of chemical nature and concentration. The level of N-methylpyrrolidone (NMP), which is a reprotoxicant Cat 1B substance, should be at minimum level. The content of inorganic impurities in HAA299 neat, specifically of Ni, Co, Cr, CD, Pb; CITATION_NUMBERS=[]; DETAILS_JSON={"cas_number":"919803-06-8","citation":"","dose":"3.4.9 Human data / 3.4.10 Special investigations / 3.5 SAFETY EVALUATION (INCLUDING CALCULATION OF THE MOS) The calculation of margin of safety (MoS) is not justified given the low dermal penetration when applied on human skin, and in consideration of the quite high NOAEL for oral administration of HAA299(nano) to rats at 1000 mg/kg bw/day.","duration":"","effect":"tential of HAA299 (nano) unlikely. 3.4.8.1 Phototoxicity/photo-irritation and photosensitisation 3.4.8.2 Photomutagenicity/photoclastogenicity / SCCS comment No photomutagenicity or photoclastogenicity tests are available for HAA299 (nano). 3.4.9 Human data / 3.4.10 Special investigations / 3.5 SAFETY EVALUATION (INCLUDING CALCULATION OF THE MOS) The calculation of margin of safety (MoS) is not justified given the low dermal penetration when applied on human skin, and in consideration of the quite high NOAEL for oral administration of HAA299(nano) to rats at 1000 mg/kg bw/day. Therefore, no concern is raised with regard to systemic toxicity. 3.6 DISCUSSION PHYSICOCHEMICAL PROPERTIES The identity of impurities that are present in batches of HAA299 (nano) must also be reported in terms of chemical nature and concentration. The level of N-methylpyrrolidone (NMP), which is a reprotoxicant Cat 1B substance, should be at minimum level. The content of inorganic impurities in HAA299 neat, specifically of Ni, Co, Cr, CD, Pb","endpoint":"irritation","ingredient":"HAA299","loael_value":"","noael_unit":"mg/kg bw/day","noael_value":"1000","page":53,"route":"oral","species":"rat","study_id":"sccs_o_256_noael_008"}
Regulatory source repeated dose toxicity 299 - - - 5 days repeated dose toxicity SOURCE_SUBDIR=sccs_o_256; REPORT_TITLE=Final Opinion Scientific Committee on Consumer Safety SCCS OPINION ON HAA299 (nano); OPINION_NUMBER=SCCS/1634/21; COMMITTEE=Scientific Committee on Consumer Safety (SCCS); REPORT_DATE=27 October 2021; VALUE_TEXT=unclear:artum, HAA299 (nano), i.e. micronised HAA299 in a formulation, C- 1332 there were no effects on mating, fertility, delivery, pup survival or development during 5 days of lactation. No histopathological lesions considered to be reflective of systemic toxicity including male and female reproductive organs were observed. Table 18: Summary of the delivery data Applicants’ conclusion on reproduction and developmental toxicity Based on the experimental conditions, the dose-level of 1000 mg a.i./kg/day was defined as No Observed Adverse Effect Level (NOAEL) for parental toxicity, reproductive performance (mating and fertility) and development. SCCS comment Based on the results on fertility and developmental parameters assessed in the repeated dose toxicity study (45 days) with the Reproduction/Developmental Toxicity Screening Test (3.4.4.2), 1000 mg a.i./kg/day is considered to be the NOAELrepro. For other endpoints see section 3.4.4.2. 3.4.5.2 Teratogenicity No teratogenicity data are available for HAA299 (nano). Some developmental aspects on HAA299 neat; DOSE=Summary of the delivery data Applicants’ conclusion on reproduction and developmental toxicity Based on the experimental conditions, the dose-level of 1000 mg a.i./kg/day was defined as No Observed Adverse Effect Level (NOAEL) for parental toxicity, reproductive performance (mating and fertility) and development.; EFFECT=artum, HAA299 (nano), i.e. micronised HAA299 in a formulation, C- 1332 there were no effects on mating, fertility, delivery, pup survival or development during 5 days of lactation. No histopathological lesions considered to be reflective of systemic toxicity including male and female reproductive organs were observed. Table 18: Summary of the delivery data Applicants’ conclusion on reproduction and developmental toxicity Based on the experimental conditions, the dose-level of 1000 mg a.i./kg/day was defined as No Observed Adverse Effect Level (NOAEL) for parental toxicity, reproductive performance (mating and fertility) and development. SCCS comment Based on the results on fertility and developmental parameters assessed in the repeated dose toxicity study (45 days) with the Reproduction/Developmental Toxicity Screening Test (3.4.4.2), 1000 mg a.i./kg/day is considered to be the NOAELrepro. For other endpoints see section 3.4.4.2. 3.4.5.2 Teratogenicity No teratogenicity data are available for HAA299 (nano). Some developmental aspects on HAA299 neat; CITATION_NUMBERS=[]; DETAILS_JSON={"cas_number":"919803-06-8","citation":"","dose":"Summary of the delivery data Applicants’ conclusion on reproduction and developmental toxicity Based on the experimental conditions, the dose-level of 1000 mg a.i./kg/day was defined as No Observed Adverse Effect Level (NOAEL) for parental toxicity, reproductive performance (mating and fertility) and development.","duration":"5 days","effect":"artum, HAA299 (nano), i.e. micronised HAA299 in a formulation, C- 1332 there were no effects on mating, fertility, delivery, pup survival or development during 5 days of lactation. No histopathological lesions considered to be reflective of systemic toxicity including male and female reproductive organs were observed. Table 18: Summary of the delivery data Applicants’ conclusion on reproduction and developmental toxicity Based on the experimental conditions, the dose-level of 1000 mg a.i./kg/day was defined as No Observed Adverse Effect Level (NOAEL) for parental toxicity, reproductive performance (mating and fertility) and development. SCCS comment Based on the results on fertility and developmental parameters assessed in the repeated dose toxicity study (45 days) with the Reproduction/Developmental Toxicity Screening Test (3.4.4.2), 1000 mg a.i./kg/day is considered to be the NOAELrepro. For other endpoints see section 3.4.4.2. 3.4.5.2 Teratogenicity No teratogenicity data are available for HAA299 (nano). Some developmental aspects on HAA299 neat","endpoint":"repeated dose toxicity","ingredient":"HAA299","loael_value":"","noael_unit":"","noael_value":"unclear:artum, HAA299 (nano), i.e. micronised HAA299 in a formulation, C- 1332 there were no effects on mating, fertility, delivery, pup survival or development during 5 days of lactation. No histopathological lesions considered to be reflective of systemic toxicity including male and female reproductive organs were observed. Table 18: Summary of the delivery data Applicants’ conclusion on reproduction and developmental toxicity Based on the experimental conditions, the dose-level of 1000 mg a.i./kg/day was defined as No Observed Adverse Effect Level (NOAEL) for parental toxicity, reproductive performance (mating and fertility) and development. SCCS comment Based on the results on fertility and developmental parameters assessed in the repeated dose toxicity study (45 days) with the Reproduction/Developmental Toxicity Screening Test (3.4.4.2), 1000 mg a.i./kg/day is considered to be the NOAELrepro. For other endpoints see section 3.4.4.2. 3.4.5.2 Teratogenicity No teratogenicity data are available for HAA299 (nano). Some developmental aspects on HAA299 neat","page":42,"route":"","species":"","study_id":"sccs_o_256_noael_006"}
Regulatory source repeated dose toxicity 299 - - - 5 days repeated dose toxicity SOURCE_SUBDIR=sccs_o_256; REPORT_TITLE=Final Opinion Scientific Committee on Consumer Safety SCCS OPINION ON HAA299 (nano); OPINION_NUMBER=SCCS/1634/21; COMMITTEE=Scientific Committee on Consumer Safety (SCCS); REPORT_DATE=27 October 2021; VALUE_TEXT=unclear:sed HAA299 in a formulation, C- 1332 there were no effects on mating, fertility, delivery, pup survival or development during 5 days of lactation. No histopathological lesions considered to be reflective of systemic toxicity including male and female reproductive organs were observed. Table 18: Summary of the delivery data Applicants’ conclusion on reproduction and developmental toxicity Based on the experimental conditions, the dose-level of 1000 mg a.i./kg/day was defined as No Observed Adverse Effect Level (NOAEL) for parental toxicity, reproductive performance (mating and fertility) and development. SCCS comment Based on the results on fertility and developmental parameters assessed in the repeated dose toxicity study (45 days) with the Reproduction/Developmental Toxicity Screening Test (3.4.4.2), 1000 mg a.i./kg/day is considered to be the NOAELrepro. For other endpoints see section 3.4.4.2. 3.4.5.2 Teratogenicity No teratogenicity data are available for HAA299 (nano). Some developmental aspects on HAA299 neat have be; DOSE=Summary of the delivery data Applicants’ conclusion on reproduction and developmental toxicity Based on the experimental conditions, the dose-level of 1000 mg a.i./kg/day was defined as No Observed Adverse Effect Level (NOAEL) for parental toxicity, reproductive performance (mating and fertility) and development.; EFFECT=sed HAA299 in a formulation, C- 1332 there were no effects on mating, fertility, delivery, pup survival or development during 5 days of lactation. No histopathological lesions considered to be reflective of systemic toxicity including male and female reproductive organs were observed. Table 18: Summary of the delivery data Applicants’ conclusion on reproduction and developmental toxicity Based on the experimental conditions, the dose-level of 1000 mg a.i./kg/day was defined as No Observed Adverse Effect Level (NOAEL) for parental toxicity, reproductive performance (mating and fertility) and development. SCCS comment Based on the results on fertility and developmental parameters assessed in the repeated dose toxicity study (45 days) with the Reproduction/Developmental Toxicity Screening Test (3.4.4.2), 1000 mg a.i./kg/day is considered to be the NOAELrepro. For other endpoints see section 3.4.4.2. 3.4.5.2 Teratogenicity No teratogenicity data are available for HAA299 (nano). Some developmental aspects on HAA299 neat have be; CITATION_NUMBERS=[]; DETAILS_JSON={"cas_number":"919803-06-8","citation":"","dose":"Summary of the delivery data Applicants’ conclusion on reproduction and developmental toxicity Based on the experimental conditions, the dose-level of 1000 mg a.i./kg/day was defined as No Observed Adverse Effect Level (NOAEL) for parental toxicity, reproductive performance (mating and fertility) and development.","duration":"5 days","effect":"sed HAA299 in a formulation, C- 1332 there were no effects on mating, fertility, delivery, pup survival or development during 5 days of lactation. No histopathological lesions considered to be reflective of systemic toxicity including male and female reproductive organs were observed. Table 18: Summary of the delivery data Applicants’ conclusion on reproduction and developmental toxicity Based on the experimental conditions, the dose-level of 1000 mg a.i./kg/day was defined as No Observed Adverse Effect Level (NOAEL) for parental toxicity, reproductive performance (mating and fertility) and development. SCCS comment Based on the results on fertility and developmental parameters assessed in the repeated dose toxicity study (45 days) with the Reproduction/Developmental Toxicity Screening Test (3.4.4.2), 1000 mg a.i./kg/day is considered to be the NOAELrepro. For other endpoints see section 3.4.4.2. 3.4.5.2 Teratogenicity No teratogenicity data are available for HAA299 (nano). Some developmental aspects on HAA299 neat have be","endpoint":"repeated dose toxicity","ingredient":"HAA299","loael_value":"","noael_unit":"","noael_value":"unclear:sed HAA299 in a formulation, C- 1332 there were no effects on mating, fertility, delivery, pup survival or development during 5 days of lactation. No histopathological lesions considered to be reflective of systemic toxicity including male and female reproductive organs were observed. Table 18: Summary of the delivery data Applicants’ conclusion on reproduction and developmental toxicity Based on the experimental conditions, the dose-level of 1000 mg a.i./kg/day was defined as No Observed Adverse Effect Level (NOAEL) for parental toxicity, reproductive performance (mating and fertility) and development. SCCS comment Based on the results on fertility and developmental parameters assessed in the repeated dose toxicity study (45 days) with the Reproduction/Developmental Toxicity Screening Test (3.4.4.2), 1000 mg a.i./kg/day is considered to be the NOAELrepro. For other endpoints see section 3.4.4.2. 3.4.5.2 Teratogenicity No teratogenicity data are available for HAA299 (nano). Some developmental aspects on HAA299 neat have be","page":42,"route":"","species":"","study_id":"sccs_o_256_noael_007"}
Regulatory source repeated dose toxicity 1000 mg/kg bw/d rat oral - repeated dose toxicity SOURCE_SUBDIR=sccs_o_159; REPORT_TITLE=OPINION ON 2-(4-(2-(4-Diethylamino-2-hydroxy-benzoyl)-benzoyl)- piperazine-1-carbonyl)-phenyl)- (4-diethylamino-2- hydroxyphenyl)-methanone (HAA299) as UV filter in sunscreen products; OPINION_NUMBER=SCCS/1533/14; COMMITTEE=Scientific Committee on Consumer Safety (SCCS); REPORT_DATE=23 September 2014; VALUE_TEXT=1000; DOSE=The calculation of margin of safety (MoS) is not justified given the low dermal penetration when applied on human skin, and in consideration of the low observed systemic toxicity (NOEL/NOAEL for oral administration of HAA299 to rats is 1000 mg/kg bw/d).; EFFECT=otosensitisation / B.3.3.10.2. Phototoxicity / photomutagenicity / photoclastogenicity / B.3.3.11. Human data / B.3.3.12. Special investigations / C.3.3.1. Safety evaluation (including calculation of the MoS) Safety evaluation of HAA299 batches containing non-nano particles can be performed on the basis of the submitted dossier: The calculation of margin of safety (MoS) is not justified given the low dermal penetration when applied on human skin, and in consideration of the low observed systemic toxicity (NOEL/NOAEL for oral administration of HAA299 to rats is 1000 mg/kg bw/d). Therefore no concern is raised with regard to systemic toxicity. Safety evaluation of HAA299 batches containing nano particles cannot be performed on the basis of the submitted dossier, because the dossier included only acute oral toxicity, acute inhalation toxicity, repeated dose toxicity and 2 in vivo mutagenicity tests. C.3.3.2. Discussion As a complete dossier of HAA299 nano-batches for safety evaluation, according to SCCS Notes of Guidan; CITATION_NUMBERS=[]; DETAILS_JSON={"cas_number":"919803-06-8","citation":"","dose":"The calculation of margin of safety (MoS) is not justified given the low dermal penetration when applied on human skin, and in consideration of the low observed systemic toxicity (NOEL/NOAEL for oral administration of HAA299 to rats is 1000 mg/kg bw/d).","duration":"","effect":"otosensitisation / B.3.3.10.2. Phototoxicity / photomutagenicity / photoclastogenicity / B.3.3.11. Human data / B.3.3.12. Special investigations / C.3.3.1. Safety evaluation (including calculation of the MoS) Safety evaluation of HAA299 batches containing non-nano particles can be performed on the basis of the submitted dossier: The calculation of margin of safety (MoS) is not justified given the low dermal penetration when applied on human skin, and in consideration of the low observed systemic toxicity (NOEL/NOAEL for oral administration of HAA299 to rats is 1000 mg/kg bw/d). Therefore no concern is raised with regard to systemic toxicity. Safety evaluation of HAA299 batches containing nano particles cannot be performed on the basis of the submitted dossier, because the dossier included only acute oral toxicity, acute inhalation toxicity, repeated dose toxicity and 2 in vivo mutagenicity tests. C.3.3.2. Discussion As a complete dossier of HAA299 nano-batches for safety evaluation, according to SCCS Notes of Guidan","endpoint":"repeated dose toxicity","ingredient":"HAA299","loael_value":"","noael_unit":"mg/kg bw/d","noael_value":"1000","page":63,"route":"oral","species":"rat","study_id":"sccs_o_159_noael_007"}
Regulatory source repeated dose toxicity 1000 mg/kg bw/d rat oral - repeated dose toxicity SOURCE_SUBDIR=sccs_o_159; REPORT_TITLE=OPINION ON 2-(4-(2-(4-Diethylamino-2-hydroxy-benzoyl)-benzoyl)- piperazine-1-carbonyl)-phenyl)- (4-diethylamino-2- hydroxyphenyl)-methanone (HAA299) as UV filter in sunscreen products; OPINION_NUMBER=SCCS/1533/14; COMMITTEE=Scientific Committee on Consumer Safety (SCCS); REPORT_DATE=23 September 2014; VALUE_TEXT=1000; DOSE=The calculation of margin of safety (MoS) is not justified given the low dermal penetration when applied on human skin, and in consideration of the low observed systemic toxicity (NOEL/NOAEL for oral administration of HAA299 to rats is 1000 mg/kg bw/d).; EFFECT=nsitisation / B.3.3.10.2. Phototoxicity / photomutagenicity / photoclastogenicity / B.3.3.11. Human data / B.3.3.12. Special investigations / C.3.3.1. Safety evaluation (including calculation of the MoS) Safety evaluation of HAA299 batches containing non-nano particles can be performed on the basis of the submitted dossier: The calculation of margin of safety (MoS) is not justified given the low dermal penetration when applied on human skin, and in consideration of the low observed systemic toxicity (NOEL/NOAEL for oral administration of HAA299 to rats is 1000 mg/kg bw/d). Therefore no concern is raised with regard to systemic toxicity. Safety evaluation of HAA299 batches containing nano particles cannot be performed on the basis of the submitted dossier, because the dossier included only acute oral toxicity, acute inhalation toxicity, repeated dose toxicity and 2 in vivo mutagenicity tests. C.3.3.2. Discussion As a complete dossier of HAA299 nano-batches for safety evaluation, according to SCCS Notes of Guidance (SC; CITATION_NUMBERS=[]; DETAILS_JSON={"cas_number":"919803-06-8","citation":"","dose":"The calculation of margin of safety (MoS) is not justified given the low dermal penetration when applied on human skin, and in consideration of the low observed systemic toxicity (NOEL/NOAEL for oral administration of HAA299 to rats is 1000 mg/kg bw/d).","duration":"","effect":"nsitisation / B.3.3.10.2. Phototoxicity / photomutagenicity / photoclastogenicity / B.3.3.11. Human data / B.3.3.12. Special investigations / C.3.3.1. Safety evaluation (including calculation of the MoS) Safety evaluation of HAA299 batches containing non-nano particles can be performed on the basis of the submitted dossier: The calculation of margin of safety (MoS) is not justified given the low dermal penetration when applied on human skin, and in consideration of the low observed systemic toxicity (NOEL/NOAEL for oral administration of HAA299 to rats is 1000 mg/kg bw/d). Therefore no concern is raised with regard to systemic toxicity. Safety evaluation of HAA299 batches containing nano particles cannot be performed on the basis of the submitted dossier, because the dossier included only acute oral toxicity, acute inhalation toxicity, repeated dose toxicity and 2 in vivo mutagenicity tests. C.3.3.2. Discussion As a complete dossier of HAA299 nano-batches for safety evaluation, according to SCCS Notes of Guidance (SC","endpoint":"repeated dose toxicity","ingredient":"HAA299","loael_value":"","noael_unit":"mg/kg bw/d","noael_value":"1000","page":63,"route":"oral","species":"rat","study_id":"sccs_o_159_noael_008"}
Regulatory source repeated dose toxicity 1000 mg/kg bw/day rat oral Subchronic repeated dose toxicity SOURCE_SUBDIR=sccs_o_159; REPORT_TITLE=OPINION ON 2-(4-(2-(4-Diethylamino-2-hydroxy-benzoyl)-benzoyl)- piperazine-1-carbonyl)-phenyl)- (4-diethylamino-2- hydroxyphenyl)-methanone (HAA299) as UV filter in sunscreen products; OPINION_NUMBER=SCCS/1533/14; COMMITTEE=Scientific Committee on Consumer Safety (SCCS); REPORT_DATE=23 September 2014; VALUE_TEXT=1000; DOSE=In terms of risk assessment, the human skin absorption will represent a small systemic exposure dose (SED) and will not allow a valid calculation of margins of safety.; EFFECT=at skin dermal absorption is around 0.5% (10 µg/cm2) of the applied amount. The human dermal skin absorption is likely to be lower than the rat skin absorption. In terms of risk assessment, the human skin absorption will represent a small systemic exposure dose (SED) and will not allow a valid calculation of margins of safety. Subchronic toxicity Sprague Dawley rats received non-micronised HAA299 by oral gavage for 13 weeks. Under the experimental conditions of this study, the No Observed (Adverse) Effect Level (NOEL/NOAEL) of HAA299 was 1000 mg/kg bw/day (highest dose tested). SCCS considers that the absence of effect observed up to the highest dose may be related to the low oral bioavailability of the substance.; CITATION_NUMBERS=[]; DETAILS_JSON={"cas_number":"919803-06-8","citation":"","dose":"In terms of risk assessment, the human skin absorption will represent a small systemic exposure dose (SED) and will not allow a valid calculation of margins of safety.","duration":"Subchronic","effect":"at skin dermal absorption is around 0.5% (10 µg/cm2) of the applied amount. The human dermal skin absorption is likely to be lower than the rat skin absorption. In terms of risk assessment, the human skin absorption will represent a small systemic exposure dose (SED) and will not allow a valid calculation of margins of safety. Subchronic toxicity Sprague Dawley rats received non-micronised HAA299 by oral gavage for 13 weeks. Under the experimental conditions of this study, the No Observed (Adverse) Effect Level (NOEL/NOAEL) of HAA299 was 1000 mg/kg bw/day (highest dose tested). SCCS considers that the absence of effect observed up to the highest dose may be related to the low oral bioavailability of the substance.","endpoint":"repeated dose toxicity","ingredient":"HAA299","loael_value":"","noael_unit":"mg/kg bw/day","noael_value":"1000","page":64,"route":"oral","species":"rat","study_id":"sccs_o_159_noael_009"}
Regulatory source repeated dose toxicity 1000 mg/kg bw/day rat oral Subchronic repeated dose toxicity SOURCE_SUBDIR=sccs_o_159; REPORT_TITLE=OPINION ON 2-(4-(2-(4-Diethylamino-2-hydroxy-benzoyl)-benzoyl)- piperazine-1-carbonyl)-phenyl)- (4-diethylamino-2- hydroxyphenyl)-methanone (HAA299) as UV filter in sunscreen products; OPINION_NUMBER=SCCS/1533/14; COMMITTEE=Scientific Committee on Consumer Safety (SCCS); REPORT_DATE=23 September 2014; VALUE_TEXT=1000; DOSE=In terms of risk assessment, the human skin absorption will represent a small systemic exposure dose (SED) and will not allow a valid calculation of margins of safety.; EFFECT=in dermal absorption is around 0.5% (10 µg/cm2) of the applied amount. The human dermal skin absorption is likely to be lower than the rat skin absorption. In terms of risk assessment, the human skin absorption will represent a small systemic exposure dose (SED) and will not allow a valid calculation of margins of safety. Subchronic toxicity Sprague Dawley rats received non-micronised HAA299 by oral gavage for 13 weeks. Under the experimental conditions of this study, the No Observed (Adverse) Effect Level (NOEL/NOAEL) of HAA299 was 1000 mg/kg bw/day (highest dose tested). SCCS considers that the absence of effect observed up to the highest dose may be related to the low oral bioavailability of the substance.; CITATION_NUMBERS=[]; DETAILS_JSON={"cas_number":"919803-06-8","citation":"","dose":"In terms of risk assessment, the human skin absorption will represent a small systemic exposure dose (SED) and will not allow a valid calculation of margins of safety.","duration":"Subchronic","effect":"in dermal absorption is around 0.5% (10 µg/cm2) of the applied amount. The human dermal skin absorption is likely to be lower than the rat skin absorption. In terms of risk assessment, the human skin absorption will represent a small systemic exposure dose (SED) and will not allow a valid calculation of margins of safety. Subchronic toxicity Sprague Dawley rats received non-micronised HAA299 by oral gavage for 13 weeks. Under the experimental conditions of this study, the No Observed (Adverse) Effect Level (NOEL/NOAEL) of HAA299 was 1000 mg/kg bw/day (highest dose tested). SCCS considers that the absence of effect observed up to the highest dose may be related to the low oral bioavailability of the substance.","endpoint":"repeated dose toxicity","ingredient":"HAA299","loael_value":"","noael_unit":"mg/kg bw/day","noael_value":"1000","page":64,"route":"oral","species":"rat","study_id":"sccs_o_159_noael_010"}
Regulatory source repeated dose toxicity 1000 mg/kg rat - 45 days repeated dose toxicity SOURCE_SUBDIR=sccs_o_256; REPORT_TITLE=Final Opinion Scientific Committee on Consumer Safety SCCS OPINION ON HAA299 (nano); OPINION_NUMBER=SCCS/1634/21; COMMITTEE=Scientific Committee on Consumer Safety (SCCS); REPORT_DATE=27 October 2021; VALUE_TEXT=1000; DOSE=Based on the experimental conditions of this study, the highest dose-level tested (1000 mg a.i./kg/day) was determined as No Observed Adverse Effect Level (NOAEL).; EFFECT=_______________________ ___________________________________________________________________________________________ 41 not elicit signs of systemic toxicity. Non-adverse clinical signs of hypersalivation, reflux at dosing and loud breathing were sporadically observed at 250 and/or 1000 mg a.i./kg/day. No histopathological lesions considered to be reflective of systemic toxicity were observed. Based on the experimental conditions of this study, the highest dose-level tested (1000 mg a.i./kg/day) was determined as No Observed Adverse Effect Level (NOAEL). Ref: CIT F-Evreux, 20 March 2009 SCCS comment In this repeated dose toxicity study (45 days), one male rat, in the highest dose, was found to show some deviation of the control parameters indicative for the presence of an inflammatory reaction (increase in WBC and PMN) while other blood values were within normal ranges. However, the histopathology did not show any organ with a severe inflammation that might explain the WBC, PMN and RTC increases in the blood. Overall, the SCCS considers 1000 mg/kg as th; CITATION=Ref: CIT F-Evreux, 20 March 2009 SCCS comment In this repeated dose toxicity study (45 days), one male rat, in the highest dose, was found to show some deviation of the control paramete; CITATION_NUMBERS=[20,2009,45]; REFERENCE=Ref: CIT F-Evreux, 20 March 2009 SCCS comment In this repeated dose toxicity study (45 days), one male rat, in the highest dose, was found to show some deviation of the control paramete; DETAILS_JSON={"cas_number":"919803-06-8","citation":"Ref: CIT F-Evreux, 20 March 2009 SCCS comment In this repeated dose toxicity study (45 days), one male rat, in the highest dose, was found to show some deviation of the control paramete","dose":"Based on the experimental conditions of this study, the highest dose-level tested (1000 mg a.i./kg/day) was determined as No Observed Adverse Effect Level (NOAEL).","duration":"45 days","effect":"_______________________ ___________________________________________________________________________________________ 41 not elicit signs of systemic toxicity. Non-adverse clinical signs of hypersalivation, reflux at dosing and loud breathing were sporadically observed at 250 and/or 1000 mg a.i./kg/day. No histopathological lesions considered to be reflective of systemic toxicity were observed. Based on the experimental conditions of this study, the highest dose-level tested (1000 mg a.i./kg/day) was determined as No Observed Adverse Effect Level (NOAEL). Ref: CIT F-Evreux, 20 March 2009 SCCS comment In this repeated dose toxicity study (45 days), one male rat, in the highest dose, was found to show some deviation of the control parameters indicative for the presence of an inflammatory reaction (increase in WBC and PMN) while other blood values were within normal ranges. However, the histopathology did not show any organ with a severe inflammation that might explain the WBC, PMN and RTC increases in the blood. Overall, the SCCS considers 1000 mg/kg as th","endpoint":"repeated dose toxicity","ingredient":"HAA299","loael_value":"","noael_unit":"mg/kg","noael_value":"1000","page":41,"route":"","species":"rat","study_id":"sccs_o_256_noael_002"}
Regulatory source repeated dose toxicity 1000 mg/kg rat - 45 days repeated dose toxicity SOURCE_SUBDIR=sccs_o_256; REPORT_TITLE=Final Opinion Scientific Committee on Consumer Safety SCCS OPINION ON HAA299 (nano); OPINION_NUMBER=SCCS/1634/21; COMMITTEE=Scientific Committee on Consumer Safety (SCCS); REPORT_DATE=27 October 2021; VALUE_TEXT=1000; DOSE=Based on the experimental conditions of this study, the highest dose-level tested (1000 mg a.i./kg/day) was determined as No Observed Adverse Effect Level (NOAEL).; EFFECT=__________________________________________________________________________________ 41 not elicit signs of systemic toxicity. Non-adverse clinical signs of hypersalivation, reflux at dosing and loud breathing were sporadically observed at 250 and/or 1000 mg a.i./kg/day. No histopathological lesions considered to be reflective of systemic toxicity were observed. Based on the experimental conditions of this study, the highest dose-level tested (1000 mg a.i./kg/day) was determined as No Observed Adverse Effect Level (NOAEL). Ref: CIT F-Evreux, 20 March 2009 SCCS comment In this repeated dose toxicity study (45 days), one male rat, in the highest dose, was found to show some deviation of the control parameters indicative for the presence of an inflammatory reaction (increase in WBC and PMN) while other blood values were within normal ranges. However, the histopathology did not show any organ with a severe inflammation that might explain the WBC, PMN and RTC increases in the blood. Overall, the SCCS considers 1000 mg/kg as the NOAEL; CITATION=Ref: CIT F-Evreux, 20 March 2009 SCCS comment In this repeated dose toxicity study (45 days), one male rat, in the highest dose, was found to show some deviation of the control paramete; CITATION_NUMBERS=[20,2009,45]; REFERENCE=Ref: CIT F-Evreux, 20 March 2009 SCCS comment In this repeated dose toxicity study (45 days), one male rat, in the highest dose, was found to show some deviation of the control paramete; DETAILS_JSON={"cas_number":"919803-06-8","citation":"Ref: CIT F-Evreux, 20 March 2009 SCCS comment In this repeated dose toxicity study (45 days), one male rat, in the highest dose, was found to show some deviation of the control paramete","dose":"Based on the experimental conditions of this study, the highest dose-level tested (1000 mg a.i./kg/day) was determined as No Observed Adverse Effect Level (NOAEL).","duration":"45 days","effect":"__________________________________________________________________________________ 41 not elicit signs of systemic toxicity. Non-adverse clinical signs of hypersalivation, reflux at dosing and loud breathing were sporadically observed at 250 and/or 1000 mg a.i./kg/day. No histopathological lesions considered to be reflective of systemic toxicity were observed. Based on the experimental conditions of this study, the highest dose-level tested (1000 mg a.i./kg/day) was determined as No Observed Adverse Effect Level (NOAEL). Ref: CIT F-Evreux, 20 March 2009 SCCS comment In this repeated dose toxicity study (45 days), one male rat, in the highest dose, was found to show some deviation of the control parameters indicative for the presence of an inflammatory reaction (increase in WBC and PMN) while other blood values were within normal ranges. However, the histopathology did not show any organ with a severe inflammation that might explain the WBC, PMN and RTC increases in the blood. Overall, the SCCS considers 1000 mg/kg as the NOAEL","endpoint":"repeated dose toxicity","ingredient":"HAA299","loael_value":"","noael_unit":"mg/kg","noael_value":"1000","page":41,"route":"","species":"rat","study_id":"sccs_o_256_noael_003"}
Regulatory source repeated dose toxicity 1000 mg/kg rat oral 45 days repeated dose toxicity SOURCE_SUBDIR=sccs_o_256; REPORT_TITLE=Final Opinion Scientific Committee on Consumer Safety SCCS OPINION ON HAA299 (nano); OPINION_NUMBER=SCCS/1634/21; COMMITTEE=Scientific Committee on Consumer Safety (SCCS); REPORT_DATE=27 October 2021; VALUE_TEXT=1000; DOSE=CIT F-Evreux, 20 March 2009 SCCS comment In this repeated dose toxicity study (45 days), one male rat, in the highest dose, was found to show some deviation of the control parameters indicative for the presence of an inflammatory reaction (increase in WBC and PMN) while other blood values were within normal ranges.; EFFECT=NOAEL). Ref: CIT F-Evreux, 20 March 2009 SCCS comment In this repeated dose toxicity study (45 days), one male rat, in the highest dose, was found to show some deviation of the control parameters indicative for the presence of an inflammatory reaction (increase in WBC and PMN) while other blood values were within normal ranges. However, the histopathology did not show any organ with a severe inflammation that might explain the WBC, PMN and RTC increases in the blood. Overall, the SCCS considers 1000 mg/kg as the NOAEL. 3.4.4.3 Sub-chronic (90 days) toxicity (oral, dermal) No sub-chronic toxicity data are available for HAA299 (nano). Applicants’ overall conclusion on repeated dose toxicity Repeated dose toxicity of HAA299 (nano), formulated as the intended commercial product for formulation of consumer sunscreens, was evaluated in a combined subacute repeated dose and reproductive toxicity screening study in Sprague-Dawley rats. Besides of non-adverse sporadic cases of in-life findings (hypersalivation, reflux at dosing and; CITATION=Ref: CIT F-Evreux, 20 March 2009 SCCS comment In this repeated dose toxicity study (45 days), one male rat, in the highest dose, was found to show some deviation of the control paramete; CITATION_NUMBERS=[20,2009,45]; REFERENCE=Ref: CIT F-Evreux, 20 March 2009 SCCS comment In this repeated dose toxicity study (45 days), one male rat, in the highest dose, was found to show some deviation of the control paramete; DETAILS_JSON={"cas_number":"919803-06-8","citation":"Ref: CIT F-Evreux, 20 March 2009 SCCS comment In this repeated dose toxicity study (45 days), one male rat, in the highest dose, was found to show some deviation of the control paramete","dose":"CIT F-Evreux, 20 March 2009 SCCS comment In this repeated dose toxicity study (45 days), one male rat, in the highest dose, was found to show some deviation of the control parameters indicative for the presence of an inflammatory reaction (increase in WBC and PMN) while other blood values were within normal ranges.","duration":"45 days","effect":"NOAEL). Ref: CIT F-Evreux, 20 March 2009 SCCS comment In this repeated dose toxicity study (45 days), one male rat, in the highest dose, was found to show some deviation of the control parameters indicative for the presence of an inflammatory reaction (increase in WBC and PMN) while other blood values were within normal ranges. However, the histopathology did not show any organ with a severe inflammation that might explain the WBC, PMN and RTC increases in the blood. Overall, the SCCS considers 1000 mg/kg as the NOAEL. 3.4.4.3 Sub-chronic (90 days) toxicity (oral, dermal) No sub-chronic toxicity data are available for HAA299 (nano). Applicants’ overall conclusion on repeated dose toxicity Repeated dose toxicity of HAA299 (nano), formulated as the intended commercial product for formulation of consumer sunscreens, was evaluated in a combined subacute repeated dose and reproductive toxicity screening study in Sprague-Dawley rats. Besides of non-adverse sporadic cases of in-life findings (hypersalivation, reflux at dosing and","endpoint":"repeated dose toxicity","ingredient":"HAA299","loael_value":"","noael_unit":"mg/kg","noael_value":"1000","page":41,"route":"oral","species":"rat","study_id":"sccs_o_256_noael_004"}
Regulatory source repeated dose toxicity 1000 mg/kg - - chronic repeated dose toxicity SOURCE_SUBDIR=sccs_o_256; REPORT_TITLE=Final Opinion Scientific Committee on Consumer Safety SCCS OPINION ON HAA299 (nano); OPINION_NUMBER=SCCS/1634/21; COMMITTEE=Scientific Committee on Consumer Safety (SCCS); REPORT_DATE=27 October 2021; VALUE_TEXT=1000; DOSE=Taking together both repeated dose toxicity studies, testing the nano and the non-nano form of HAA299, does not show any toxicity after repeated exposure.; EFFECT=for the absence of systemic toxicity, the sub- chronic application of HAA299 (nano) is not expected to show such effects. Taking together both repeated dose toxicity studies, testing the nano and the non-nano form of HAA299, does not show any toxicity after repeated exposure. Overall SCCS comment on repeated dose toxicity No sub-chronic toxicity data were provided for HAA299 (nano). However, from the Combined Repeated Dose Toxicity Study with the Reproduction/Developmental Toxicity Screening Test (OECD TG 422), a NOAEL value of 1000 mg/kg could be derived.; CITATION_NUMBERS=[]; DETAILS_JSON={"cas_number":"919803-06-8","citation":"","dose":"Taking together both repeated dose toxicity studies, testing the nano and the non-nano form of HAA299, does not show any toxicity after repeated exposure.","duration":"chronic","effect":"for the absence of systemic toxicity, the sub- chronic application of HAA299 (nano) is not expected to show such effects. Taking together both repeated dose toxicity studies, testing the nano and the non-nano form of HAA299, does not show any toxicity after repeated exposure. Overall SCCS comment on repeated dose toxicity No sub-chronic toxicity data were provided for HAA299 (nano). However, from the Combined Repeated Dose Toxicity Study with the Reproduction/Developmental Toxicity Screening Test (OECD TG 422), a NOAEL value of 1000 mg/kg could be derived.","endpoint":"repeated dose toxicity","ingredient":"HAA299","loael_value":"","noael_unit":"mg/kg","noael_value":"1000","page":41,"route":"","species":"","study_id":"sccs_o_256_noael_005"}
Regulatory source repeated dose toxicity 1000 mg/kg rat oral 45 days repeated dose toxicity SOURCE_SUBDIR=sccs_o_256; REPORT_TITLE=Final Opinion Scientific Committee on Consumer Safety SCCS OPINION ON HAA299 (nano); OPINION_NUMBER=SCCS/1634/21; COMMITTEE=Scientific Committee on Consumer Safety (SCCS); REPORT_DATE=27 October 2021; VALUE_TEXT=1000; DOSE=Repeated dose oral toxicity In the repeated dose toxicity study (45 days) submitted by the Applicant, one male rat, in the highest dose, was found to show some deviation of the control parameters indicative for the presence of an inflammatory reaction (increase in WBC and PMN) while other blood values were within normal ranges.; EFFECT=. Repeated dose oral toxicity In the repeated dose toxicity study (45 days) submitted by the Applicant, one male rat, in the highest dose, was found to show some deviation of the control parameters indicative for the presence of an inflammatory reaction (increase in WBC and PMN) while other blood values were within normal ranges. However, the histopathology did not show any organ with a severe inflammation that might explain the WBC, PMN and RTC increase in the blood. Overall, the SCCS considers 1000 mg/kg as the NOAEL. Sub-chronic toxicity No sub-chronic toxicity data were provided for HAA299 (nano). However, from the Combined Repeated Dose Toxicity Study (45 days), with the Reproduction/Developmental Toxicity Screening Test (OECD TG 422), a NOAEL value of 1000 mg/kg could be derived. Reproductive toxicity A dose-level of 1000 mg a.i./kg/day was defined as NOAEL for fertility and developmental effects. No teratogenicity data are available for HAA299 (nano). Mutagenicity/genotoxicity HAA299 (nano) did not induce any biologica; CITATION_NUMBERS=[]; DETAILS_JSON={"cas_number":"919803-06-8","citation":"","dose":"Repeated dose oral toxicity In the repeated dose toxicity study (45 days) submitted by the Applicant, one male rat, in the highest dose, was found to show some deviation of the control parameters indicative for the presence of an inflammatory reaction (increase in WBC and PMN) while other blood values were within normal ranges.","duration":"45 days","effect":". Repeated dose oral toxicity In the repeated dose toxicity study (45 days) submitted by the Applicant, one male rat, in the highest dose, was found to show some deviation of the control parameters indicative for the presence of an inflammatory reaction (increase in WBC and PMN) while other blood values were within normal ranges. However, the histopathology did not show any organ with a severe inflammation that might explain the WBC, PMN and RTC increase in the blood. Overall, the SCCS considers 1000 mg/kg as the NOAEL. Sub-chronic toxicity No sub-chronic toxicity data were provided for HAA299 (nano). However, from the Combined Repeated Dose Toxicity Study (45 days), with the Reproduction/Developmental Toxicity Screening Test (OECD TG 422), a NOAEL value of 1000 mg/kg could be derived. Reproductive toxicity A dose-level of 1000 mg a.i./kg/day was defined as NOAEL for fertility and developmental effects. No teratogenicity data are available for HAA299 (nano). Mutagenicity/genotoxicity HAA299 (nano) did not induce any biologica","endpoint":"repeated dose toxicity","ingredient":"HAA299","loael_value":"","noael_unit":"mg/kg","noael_value":"1000","page":55,"route":"oral","species":"rat","study_id":"sccs_o_256_noael_009"}
Regulatory source repeated dose toxicity 1000 mg/kg - - Sub-chronic repeated dose toxicity SOURCE_SUBDIR=sccs_o_256; REPORT_TITLE=Final Opinion Scientific Committee on Consumer Safety SCCS OPINION ON HAA299 (nano); OPINION_NUMBER=SCCS/1634/21; COMMITTEE=Scientific Committee on Consumer Safety (SCCS); REPORT_DATE=27 October 2021; VALUE_TEXT=1000; DOSE=Overall, the SCCS considers 1000 mg/kg as the NOAEL.; EFFECT=flammatory reaction (increase in WBC and PMN) while other blood values were within normal ranges. However, the histopathology did not show any organ with a severe inflammation that might explain the WBC, PMN and RTC increase in the blood. Overall, the SCCS considers 1000 mg/kg as the NOAEL. Sub-chronic toxicity No sub-chronic toxicity data were provided for HAA299 (nano). However, from the Combined Repeated Dose Toxicity Study (45 days), with the Reproduction/Developmental Toxicity Screening Test (OECD TG 422), a NOAEL value of 1000 mg/kg could be derived. Reproductive toxicity A dose-level of 1000 mg a.i./kg/day was defined as NOAEL for fertility and developmental effects. No teratogenicity data are available for HAA299 (nano). Mutagenicity/genotoxicity HAA299 (nano) did not induce any biologically meaningful increase in mutant frequency in the in vitro HPRT test on CHO cells and in the micronucleus test on V79 lung fibroblasts. However, in view of the lack of any evidence of cell internalisation of the test item the results; CITATION_NUMBERS=[]; DETAILS_JSON={"cas_number":"919803-06-8","citation":"","dose":"Overall, the SCCS considers 1000 mg/kg as the NOAEL.","duration":"Sub-chronic","effect":"flammatory reaction (increase in WBC and PMN) while other blood values were within normal ranges. However, the histopathology did not show any organ with a severe inflammation that might explain the WBC, PMN and RTC increase in the blood. Overall, the SCCS considers 1000 mg/kg as the NOAEL. Sub-chronic toxicity No sub-chronic toxicity data were provided for HAA299 (nano). However, from the Combined Repeated Dose Toxicity Study (45 days), with the Reproduction/Developmental Toxicity Screening Test (OECD TG 422), a NOAEL value of 1000 mg/kg could be derived. Reproductive toxicity A dose-level of 1000 mg a.i./kg/day was defined as NOAEL for fertility and developmental effects. No teratogenicity data are available for HAA299 (nano). Mutagenicity/genotoxicity HAA299 (nano) did not induce any biologically meaningful increase in mutant frequency in the in vitro HPRT test on CHO cells and in the micronucleus test on V79 lung fibroblasts. However, in view of the lack of any evidence of cell internalisation of the test item the results","endpoint":"repeated dose toxicity","ingredient":"HAA299","loael_value":"","noael_unit":"mg/kg","noael_value":"1000","page":55,"route":"","species":"","study_id":"sccs_o_256_noael_010"}
Regulatory source repeated dose toxicity 1000 mg/kg - - Sub-chronic repeated dose toxicity SOURCE_SUBDIR=sccs_o_256; REPORT_TITLE=Final Opinion Scientific Committee on Consumer Safety SCCS OPINION ON HAA299 (nano); OPINION_NUMBER=SCCS/1634/21; COMMITTEE=Scientific Committee on Consumer Safety (SCCS); REPORT_DATE=27 October 2021; VALUE_TEXT=1000; DOSE=Overall, the SCCS considers 1000 mg/kg as the NOAEL.; EFFECT=thology did not show any organ with a severe inflammation that might explain the WBC, PMN and RTC increase in the blood. Overall, the SCCS considers 1000 mg/kg as the NOAEL. Sub-chronic toxicity No sub-chronic toxicity data were provided for HAA299 (nano). However, from the Combined Repeated Dose Toxicity Study (45 days), with the Reproduction/Developmental Toxicity Screening Test (OECD TG 422), a NOAEL value of 1000 mg/kg could be derived. Reproductive toxicity A dose-level of 1000 mg a.i./kg/day was defined as NOAEL for fertility and developmental effects. No teratogenicity data are available for HAA299 (nano). Mutagenicity/genotoxicity HAA299 (nano) did not induce any biologically meaningful increase in mutant frequency in the in vitro HPRT test on CHO cells and in the micronucleus test on V79 lung fibroblasts. However, in view of the lack of any evidence of cell internalisation of the test item the results should be regarded as inconclusive. As clearly delineated in the SCCS Guidance on the Safety Assessment of Nanomateria; CITATION_NUMBERS=[]; DETAILS_JSON={"cas_number":"919803-06-8","citation":"","dose":"Overall, the SCCS considers 1000 mg/kg as the NOAEL.","duration":"Sub-chronic","effect":"thology did not show any organ with a severe inflammation that might explain the WBC, PMN and RTC increase in the blood. Overall, the SCCS considers 1000 mg/kg as the NOAEL. Sub-chronic toxicity No sub-chronic toxicity data were provided for HAA299 (nano). However, from the Combined Repeated Dose Toxicity Study (45 days), with the Reproduction/Developmental Toxicity Screening Test (OECD TG 422), a NOAEL value of 1000 mg/kg could be derived. Reproductive toxicity A dose-level of 1000 mg a.i./kg/day was defined as NOAEL for fertility and developmental effects. No teratogenicity data are available for HAA299 (nano). Mutagenicity/genotoxicity HAA299 (nano) did not induce any biologically meaningful increase in mutant frequency in the in vitro HPRT test on CHO cells and in the micronucleus test on V79 lung fibroblasts. However, in view of the lack of any evidence of cell internalisation of the test item the results should be regarded as inconclusive. As clearly delineated in the SCCS Guidance on the Safety Assessment of Nanomateria","endpoint":"repeated dose toxicity","ingredient":"HAA299","loael_value":"","noael_unit":"mg/kg","noael_value":"1000","page":55,"route":"","species":"","study_id":"sccs_o_256_noael_011"}
Regulatory source reproductive toxicity 1000 mg/kg bw/day rat - - reproductive toxicity SOURCE_SUBDIR=sccs_o_159; REPORT_TITLE=OPINION ON 2-(4-(2-(4-Diethylamino-2-hydroxy-benzoyl)-benzoyl)- piperazine-1-carbonyl)-phenyl)- (4-diethylamino-2- hydroxyphenyl)-methanone (HAA299) as UV filter in sunscreen products; OPINION_NUMBER=SCCS/1533/14; COMMITTEE=Scientific Committee on Consumer Safety (SCCS); REPORT_DATE=23 September 2014; VALUE_TEXT=1000; DOSE=from group 3 (50 mg/kg bw/day) and two rats from group 5 (1000 mg/kg bw/day).; EFFECT=from group 3 (50 mg/kg bw/day) and two rats from group 5 (1000 mg/kg bw/day). The study authors write that this change was considered unrelated to treatment with the test item as it is considered to be a spontaneous change occasionally seen in untreated rats, that it was poorly dose-related, generally unilateral and also noted in one rat given placebo mix. Conclusion The study authors concluded that based on the experimental conditions of this study, the dose-level of 1000 mg a.i./kg/day was considered to be the No Observed Adverse Effect Level (NOAEL) for parental toxicity and the No Observed Effect Level (NOEL) for reproductive performance (mating and fertility). Ref.: 21 SCCS comment The absence of effect observed up to the highest dose may be related to the low bioavailability. B.3.3.8.1. Two generation reproduction toxicity /; CITATION=Ref.: 21 SCCS comment The absence of effect observed up to the highest dose may be related to the low bioavailability; CITATION_NUMBERS=[21]; REFERENCE=Ref.: 21 SCCS comment The absence of effect observed up to the highest dose may be related to the low bioavailability; DETAILS_JSON={"cas_number":"919803-06-8","citation":"Ref.: 21 SCCS comment The absence of effect observed up to the highest dose may be related to the low bioavailability","dose":"from group 3 (50 mg/kg bw/day) and two rats from group 5 (1000 mg/kg bw/day).","duration":"","effect":"from group 3 (50 mg/kg bw/day) and two rats from group 5 (1000 mg/kg bw/day). The study authors write that this change was considered unrelated to treatment with the test item as it is considered to be a spontaneous change occasionally seen in untreated rats, that it was poorly dose-related, generally unilateral and also noted in one rat given placebo mix. Conclusion The study authors concluded that based on the experimental conditions of this study, the dose-level of 1000 mg a.i./kg/day was considered to be the No Observed Adverse Effect Level (NOAEL) for parental toxicity and the No Observed Effect Level (NOEL) for reproductive performance (mating and fertility). Ref.: 21 SCCS comment The absence of effect observed up to the highest dose may be related to the low bioavailability. B.3.3.8.1. Two generation reproduction toxicity /","endpoint":"reproductive toxicity","ingredient":"HAA299","loael_value":"","noael_unit":"mg/kg bw/day","noael_value":"1000","page":62,"route":"","species":"rat","study_id":"sccs_o_159_noael_004"}
Regulatory source reproductive toxicity 1000 mg/kg bw/day rat - - reproductive toxicity SOURCE_SUBDIR=sccs_o_159; REPORT_TITLE=OPINION ON 2-(4-(2-(4-Diethylamino-2-hydroxy-benzoyl)-benzoyl)- piperazine-1-carbonyl)-phenyl)- (4-diethylamino-2- hydroxyphenyl)-methanone (HAA299) as UV filter in sunscreen products; OPINION_NUMBER=SCCS/1533/14; COMMITTEE=Scientific Committee on Consumer Safety (SCCS); REPORT_DATE=23 September 2014; VALUE_TEXT=1000; DOSE=two rats from group 5 (1000 mg/kg bw/day).; EFFECT=two rats from group 5 (1000 mg/kg bw/day). The study authors write that this change was considered unrelated to treatment with the test item as it is considered to be a spontaneous change occasionally seen in untreated rats, that it was poorly dose-related, generally unilateral and also noted in one rat given placebo mix. Conclusion The study authors concluded that based on the experimental conditions of this study, the dose-level of 1000 mg a.i./kg/day was considered to be the No Observed Adverse Effect Level (NOAEL) for parental toxicity and the No Observed Effect Level (NOEL) for reproductive performance (mating and fertility). Ref.: 21 SCCS comment The absence of effect observed up to the highest dose may be related to the low bioavailability. B.3.3.8.1. Two generation reproduction toxicity /; CITATION=Ref.: 21 SCCS comment The absence of effect observed up to the highest dose may be related to the low bioavailability; CITATION_NUMBERS=[21]; REFERENCE=Ref.: 21 SCCS comment The absence of effect observed up to the highest dose may be related to the low bioavailability; DETAILS_JSON={"cas_number":"919803-06-8","citation":"Ref.: 21 SCCS comment The absence of effect observed up to the highest dose may be related to the low bioavailability","dose":"two rats from group 5 (1000 mg/kg bw/day).","duration":"","effect":"two rats from group 5 (1000 mg/kg bw/day). The study authors write that this change was considered unrelated to treatment with the test item as it is considered to be a spontaneous change occasionally seen in untreated rats, that it was poorly dose-related, generally unilateral and also noted in one rat given placebo mix. Conclusion The study authors concluded that based on the experimental conditions of this study, the dose-level of 1000 mg a.i./kg/day was considered to be the No Observed Adverse Effect Level (NOAEL) for parental toxicity and the No Observed Effect Level (NOEL) for reproductive performance (mating and fertility). Ref.: 21 SCCS comment The absence of effect observed up to the highest dose may be related to the low bioavailability. B.3.3.8.1. Two generation reproduction toxicity /","endpoint":"reproductive toxicity","ingredient":"HAA299","loael_value":"","noael_unit":"mg/kg bw/day","noael_value":"1000","page":62,"route":"","species":"rat","study_id":"sccs_o_159_noael_005"}
Regulatory source reproductive toxicity 1000 - rat - - reproductive toxicity SOURCE_SUBDIR=sccs_o_159; REPORT_TITLE=OPINION ON 2-(4-(2-(4-Diethylamino-2-hydroxy-benzoyl)-benzoyl)- piperazine-1-carbonyl)-phenyl)- (4-diethylamino-2- hydroxyphenyl)-methanone (HAA299) as UV filter in sunscreen products; OPINION_NUMBER=SCCS/1533/14; COMMITTEE=Scientific Committee on Consumer Safety (SCCS); REPORT_DATE=23 September 2014; VALUE_TEXT=unclear:rite that this change was considered unrelated to treatment with the test item as it is considered to be a spontaneous change occasionally seen in untreated rats, that it was poorly dose-related, generally unilateral and also noted in one rat given placebo mix. Conclusion The study authors concluded that based on the experimental conditions of this study, the dose-level of 1000 mg a.i./kg/day was considered to be the No Observed Adverse Effect Level (NOAEL) for parental toxicity and the No Observed Effect Level (NOEL) for reproductive performance (mating and fertility). Ref.: 21 SCCS comment The absence of effect observed up to the highest dose may be related to the low bioavailability. B.3.3.8.1. Two generation reproduction toxicity /; DOSE=rite that this change was considered unrelated to treatment with the test item as it is considered to be a spontaneous change occasionally seen in untreated rats, that it was poorly dose-related, generally unilateral and also noted in one rat given placebo mix.; EFFECT=rite that this change was considered unrelated to treatment with the test item as it is considered to be a spontaneous change occasionally seen in untreated rats, that it was poorly dose-related, generally unilateral and also noted in one rat given placebo mix. Conclusion The study authors concluded that based on the experimental conditions of this study, the dose-level of 1000 mg a.i./kg/day was considered to be the No Observed Adverse Effect Level (NOAEL) for parental toxicity and the No Observed Effect Level (NOEL) for reproductive performance (mating and fertility). Ref.: 21 SCCS comment The absence of effect observed up to the highest dose may be related to the low bioavailability. B.3.3.8.1. Two generation reproduction toxicity /; CITATION=Ref.: 21 SCCS comment The absence of effect observed up to the highest dose may be related to the low bioavailability; CITATION_NUMBERS=[21]; REFERENCE=Ref.: 21 SCCS comment The absence of effect observed up to the highest dose may be related to the low bioavailability; DETAILS_JSON={"cas_number":"919803-06-8","citation":"Ref.: 21 SCCS comment The absence of effect observed up to the highest dose may be related to the low bioavailability","dose":"rite that this change was considered unrelated to treatment with the test item as it is considered to be a spontaneous change occasionally seen in untreated rats, that it was poorly dose-related, generally unilateral and also noted in one rat given placebo mix.","duration":"","effect":"rite that this change was considered unrelated to treatment with the test item as it is considered to be a spontaneous change occasionally seen in untreated rats, that it was poorly dose-related, generally unilateral and also noted in one rat given placebo mix. Conclusion The study authors concluded that based on the experimental conditions of this study, the dose-level of 1000 mg a.i./kg/day was considered to be the No Observed Adverse Effect Level (NOAEL) for parental toxicity and the No Observed Effect Level (NOEL) for reproductive performance (mating and fertility). Ref.: 21 SCCS comment The absence of effect observed up to the highest dose may be related to the low bioavailability. B.3.3.8.1. Two generation reproduction toxicity /","endpoint":"reproductive toxicity","ingredient":"HAA299","loael_value":"","noael_unit":"","noael_value":"unclear:rite that this change was considered unrelated to treatment with the test item as it is considered to be a spontaneous change occasionally seen in untreated rats, that it was poorly dose-related, generally unilateral and also noted in one rat given placebo mix. Conclusion The study authors concluded that based on the experimental conditions of this study, the dose-level of 1000 mg a.i./kg/day was considered to be the No Observed Adverse Effect Level (NOAEL) for parental toxicity and the No Observed Effect Level (NOEL) for reproductive performance (mating and fertility). Ref.: 21 SCCS comment The absence of effect observed up to the highest dose may be related to the low bioavailability. B.3.3.8.1. Two generation reproduction toxicity /","page":62,"route":"","species":"rat","study_id":"sccs_o_159_noael_006"}
Regulatory source reproductive toxicity 1000 mg/kg bw/day rat oral developmental reproductive toxicity SOURCE_SUBDIR=sccs_o_159; REPORT_TITLE=OPINION ON 2-(4-(2-(4-Diethylamino-2-hydroxy-benzoyl)-benzoyl)- piperazine-1-carbonyl)-phenyl)- (4-diethylamino-2- hydroxyphenyl)-methanone (HAA299) as UV filter in sunscreen products; OPINION_NUMBER=SCCS/1533/14; COMMITTEE=Scientific Committee on Consumer Safety (SCCS); REPORT_DATE=23 September 2014; VALUE_TEXT=1000; DOSE=The HAA299 was well tolerated by the dams, with no (adverse) effects at any dose-level.; EFFECT=SCCS/1533/14 Revision of the Opinion on the safety of HAA299 as UV filter in sunscreen products ___________________________________________________________________________________________ 65 Reproductive toxicity The teratogenicity of non-nano HAA299 was tested by oral administration on days 6 – 20 post-coitum. The HAA299 was well tolerated by the dams, with no (adverse) effects at any dose-level. Fetal examination resulted in no treatment-related malformations or variations at any dose-level. NOEL/NOAEL for both the maternal toxicity and the developmental toxicity was identified at 1000 mg/kg bw/day (highest dose tested). SCCS considers that the absence of effect observed up to the highest dose may be related to the low oral bioavailability of the substance. A further study was performed with nano form of HAA299: the objective of the study was to evaluate the potential toxic effects following daily oral gavage administration to male and female rats from 15 days before mating, through mating (up to 3 weeks); CITATION_NUMBERS=[]; DETAILS_JSON={"cas_number":"919803-06-8","citation":"","dose":"The HAA299 was well tolerated by the dams, with no (adverse) effects at any dose-level.","duration":"developmental","effect":"SCCS/1533/14 Revision of the Opinion on the safety of HAA299 as UV filter in sunscreen products ___________________________________________________________________________________________ 65 Reproductive toxicity The teratogenicity of non-nano HAA299 was tested by oral administration on days 6 – 20 post-coitum. The HAA299 was well tolerated by the dams, with no (adverse) effects at any dose-level. Fetal examination resulted in no treatment-related malformations or variations at any dose-level. NOEL/NOAEL for both the maternal toxicity and the developmental toxicity was identified at 1000 mg/kg bw/day (highest dose tested). SCCS considers that the absence of effect observed up to the highest dose may be related to the low oral bioavailability of the substance. A further study was performed with nano form of HAA299: the objective of the study was to evaluate the potential toxic effects following daily oral gavage administration to male and female rats from 15 days before mating, through mating (up to 3 weeks)","endpoint":"reproductive toxicity","ingredient":"HAA299","loael_value":"","noael_unit":"mg/kg bw/day","noael_value":"1000","page":65,"route":"oral","species":"rat","study_id":"sccs_o_159_noael_011"}
Regulatory source reproductive toxicity 1000 mg/kg bw/day rat oral 15 days reproductive toxicity SOURCE_SUBDIR=sccs_o_159; REPORT_TITLE=OPINION ON 2-(4-(2-(4-Diethylamino-2-hydroxy-benzoyl)-benzoyl)- piperazine-1-carbonyl)-phenyl)- (4-diethylamino-2- hydroxyphenyl)-methanone (HAA299) as UV filter in sunscreen products; OPINION_NUMBER=SCCS/1533/14; COMMITTEE=Scientific Committee on Consumer Safety (SCCS); REPORT_DATE=23 September 2014; VALUE_TEXT=1000; DOSE=(highest dose tested).; EFFECT=(highest dose tested). SCCS considers that the absence of effect observed up to the highest dose may be related to the low oral bioavailability of the substance. A further study was performed with nano form of HAA299: the objective of the study was to evaluate the potential toxic effects following daily oral gavage administration to male and female rats from 15 days before mating, through mating (up to 3 weeks) and in addition for the females, during pregnancy and lactation, until day 5 post-partum inclusive. The NOEL/NOAEL of nano HAA299 for parental toxicity and for reproductive performance (mating and fertility) was 1000 mg/kg bw/day (highest dose tested). Mutagenicity / genotoxicity Non-micronised HAA299 was tested in vitro for mutagenic activity in a bacterial reverse mutation tests, a mutagenicity test in mammalian cells (mouse lymphoma assay) and a mammalian test for chromosome aberration. All tests were negative. Non-micronised HAA299 was also tested with rats in an in vivo unscheduled DNA synthesis test and with mous; CITATION_NUMBERS=[]; DETAILS_JSON={"cas_number":"919803-06-8","citation":"","dose":"(highest dose tested).","duration":"15 days","effect":"(highest dose tested). SCCS considers that the absence of effect observed up to the highest dose may be related to the low oral bioavailability of the substance. A further study was performed with nano form of HAA299: the objective of the study was to evaluate the potential toxic effects following daily oral gavage administration to male and female rats from 15 days before mating, through mating (up to 3 weeks) and in addition for the females, during pregnancy and lactation, until day 5 post-partum inclusive. The NOEL/NOAEL of nano HAA299 for parental toxicity and for reproductive performance (mating and fertility) was 1000 mg/kg bw/day (highest dose tested). Mutagenicity / genotoxicity Non-micronised HAA299 was tested in vitro for mutagenic activity in a bacterial reverse mutation tests, a mutagenicity test in mammalian cells (mouse lymphoma assay) and a mammalian test for chromosome aberration. All tests were negative. Non-micronised HAA299 was also tested with rats in an in vivo unscheduled DNA synthesis test and with mous","endpoint":"reproductive toxicity","ingredient":"HAA299","loael_value":"","noael_unit":"mg/kg bw/day","noael_value":"1000","page":65,"route":"oral","species":"rat","study_id":"sccs_o_159_noael_012"}
Regulatory source reproductive toxicity 1000 mg/kg bw/day rat oral 15 days reproductive toxicity SOURCE_SUBDIR=sccs_o_159; REPORT_TITLE=OPINION ON 2-(4-(2-(4-Diethylamino-2-hydroxy-benzoyl)-benzoyl)- piperazine-1-carbonyl)-phenyl)- (4-diethylamino-2- hydroxyphenyl)-methanone (HAA299) as UV filter in sunscreen products; OPINION_NUMBER=SCCS/1533/14; COMMITTEE=Scientific Committee on Consumer Safety (SCCS); REPORT_DATE=23 September 2014; VALUE_TEXT=1000; DOSE=SCCS considers that the absence of effect observed up to the highest dose may be related to the low oral bioavailability of the substance.; EFFECT=est dose tested). SCCS considers that the absence of effect observed up to the highest dose may be related to the low oral bioavailability of the substance. A further study was performed with nano form of HAA299: the objective of the study was to evaluate the potential toxic effects following daily oral gavage administration to male and female rats from 15 days before mating, through mating (up to 3 weeks) and in addition for the females, during pregnancy and lactation, until day 5 post-partum inclusive. The NOEL/NOAEL of nano HAA299 for parental toxicity and for reproductive performance (mating and fertility) was 1000 mg/kg bw/day (highest dose tested). Mutagenicity / genotoxicity Non-micronised HAA299 was tested in vitro for mutagenic activity in a bacterial reverse mutation tests, a mutagenicity test in mammalian cells (mouse lymphoma assay) and a mammalian test for chromosome aberration. All tests were negative. Non-micronised HAA299 was also tested with rats in an in vivo unscheduled DNA synthesis test and with mouse in a; CITATION_NUMBERS=[]; DETAILS_JSON={"cas_number":"919803-06-8","citation":"","dose":"SCCS considers that the absence of effect observed up to the highest dose may be related to the low oral bioavailability of the substance.","duration":"15 days","effect":"est dose tested). SCCS considers that the absence of effect observed up to the highest dose may be related to the low oral bioavailability of the substance. A further study was performed with nano form of HAA299: the objective of the study was to evaluate the potential toxic effects following daily oral gavage administration to male and female rats from 15 days before mating, through mating (up to 3 weeks) and in addition for the females, during pregnancy and lactation, until day 5 post-partum inclusive. The NOEL/NOAEL of nano HAA299 for parental toxicity and for reproductive performance (mating and fertility) was 1000 mg/kg bw/day (highest dose tested). Mutagenicity / genotoxicity Non-micronised HAA299 was tested in vitro for mutagenic activity in a bacterial reverse mutation tests, a mutagenicity test in mammalian cells (mouse lymphoma assay) and a mammalian test for chromosome aberration. All tests were negative. Non-micronised HAA299 was also tested with rats in an in vivo unscheduled DNA synthesis test and with mouse in a","endpoint":"reproductive toxicity","ingredient":"HAA299","loael_value":"","noael_unit":"mg/kg bw/day","noael_value":"1000","page":65,"route":"oral","species":"rat","study_id":"sccs_o_159_noael_013"}
Regulatory source reproductive toxicity 1000 mg/kg/day - oral - reproductive toxicity SOURCE_SUBDIR=sccs_o_256; REPORT_TITLE=Final Opinion Scientific Committee on Consumer Safety SCCS OPINION ON HAA299 (nano); OPINION_NUMBER=SCCS/1634/21; COMMITTEE=Scientific Committee on Consumer Safety (SCCS); REPORT_DATE=27 October 2021; VALUE_TEXT=1000; DOSE=The NOAEL of 1000 mg/kg/day indicates that the material is of overall low toxicological concern.; EFFECT=SCCS-rejected applicant NOAEL: __________________________________________________________ 3 1. ABSTRACT The SCCS concludes the following: 1. In light of the data provided, does the SCCS consider HAA299 (nano) safe when used as a UV-filter in cosmetic products up to a maximum concentration of 10%? The available data indicate that HAA299 (nano) is a practically insoluble material, with very low dermal and oral absorption. Due to the very low systemic availability, the material is unlikely to exert systemic genotoxic or reproductive effects. The NOAEL of 1000 mg/kg/day indicates that the material is of overall low toxicological concern. Given the low dermal penetration, and low systemic toxicity, the calculation of margin of safety (MoS) is not appropriate in this case. The SCCS considers that HAA299 (nano) as covered within the provided characteristics (minimum purity equal to or above 97%, median particle size in terms of particle number equal to or above 50 nm) is safe when used as a UV-filter in dermally-applied cosmetic products up to a maximum concentrati; CITATION_NUMBERS=[]; DETAILS_JSON={"cas_number":"919803-06-8","citation":"","dose":"The NOAEL of 1000 mg/kg/day indicates that the material is of overall low toxicological concern.","duration":"","effect":"SCCS-rejected applicant NOAEL: __________________________________________________________ 3 1. ABSTRACT The SCCS concludes the following: 1. In light of the data provided, does the SCCS consider HAA299 (nano) safe when used as a UV-filter in cosmetic products up to a maximum concentration of 10%? The available data indicate that HAA299 (nano) is a practically insoluble material, with very low dermal and oral absorption. Due to the very low systemic availability, the material is unlikely to exert systemic genotoxic or reproductive effects. The NOAEL of 1000 mg/kg/day indicates that the material is of overall low toxicological concern. Given the low dermal penetration, and low systemic toxicity, the calculation of margin of safety (MoS) is not appropriate in this case. The SCCS considers that HAA299 (nano) as covered within the provided characteristics (minimum purity equal to or above 97%, median particle size in terms of particle number equal to or above 50 nm) is safe when used as a UV-filter in dermally-applied cosmetic products up to a maximum concentrati","endpoint":"reproductive toxicity","ingredient":"HAA299","loael_value":"","noael_unit":"mg/kg/day","noael_value":"1000","page":3,"route":"oral","species":"","study_id":"sccs_o_256_noael_001"}
Regulatory source reproductive toxicity 1000 mg/kg/day - oral - reproductive toxicity SOURCE_SUBDIR=sccs_o_256; REPORT_TITLE=Final Opinion Scientific Committee on Consumer Safety SCCS OPINION ON HAA299 (nano); OPINION_NUMBER=SCCS/1634/21; COMMITTEE=Scientific Committee on Consumer Safety (SCCS); REPORT_DATE=27 October 2021; VALUE_TEXT=1000; DOSE=The NOAEL of 1000 mg/kg/day indicates that the material is of overall low toxicological concern.; EFFECT=SCCS-rejected applicant NOAEL: _________________________________________________________________________________________ 56 4. CONCLUSION 1. In light of the data provided, does the SCCS consider HAA299 (nano) safe when used as a UV-filter in cosmetic products up to a maximum concentration of 10%? The available data indicate that HAA299 (nano) is a practically insoluble material, with very low dermal and oral absorption. Due to the very low systemic availability, the material is unlikely to exert systemic genotoxic or reproductive effects. The NOAEL of 1000 mg/kg/day indicates that the material is of overall low toxicological concern. Given the low dermal penetration, and low systemic toxicity, the calculation of margin of safety (MoS) is not appropriate in this case. The SCCS considers that HAA299 (nano), as covered within the provided characteristics (minimum purity equal to or above 97%, median particle size in terms of particle number equal to or above 50 nm), is safe when used as a UV-filter in dermally-applied cosmetic products up to a maximum concentra; CITATION_NUMBERS=[]; DETAILS_JSON={"cas_number":"919803-06-8","citation":"","dose":"The NOAEL of 1000 mg/kg/day indicates that the material is of overall low toxicological concern.","duration":"","effect":"SCCS-rejected applicant NOAEL: _________________________________________________________________________________________ 56 4. CONCLUSION 1. In light of the data provided, does the SCCS consider HAA299 (nano) safe when used as a UV-filter in cosmetic products up to a maximum concentration of 10%? The available data indicate that HAA299 (nano) is a practically insoluble material, with very low dermal and oral absorption. Due to the very low systemic availability, the material is unlikely to exert systemic genotoxic or reproductive effects. The NOAEL of 1000 mg/kg/day indicates that the material is of overall low toxicological concern. Given the low dermal penetration, and low systemic toxicity, the calculation of margin of safety (MoS) is not appropriate in this case. The SCCS considers that HAA299 (nano), as covered within the provided characteristics (minimum purity equal to or above 97%, median particle size in terms of particle number equal to or above 50 nm), is safe when used as a UV-filter in dermally-applied cosmetic products up to a maximum concentra","endpoint":"reproductive toxicity","ingredient":"HAA299","loael_value":"","noael_unit":"mg/kg/day","noael_value":"1000","page":56,"route":"oral","species":"","study_id":"sccs_o_256_noael_012"}