NOAEL Studies Cosmetic Ingredient

Methylimidazoliumpropyl p-Phenylenediamine HCl NOAEL Studies

INCI: METHYLIMIDAZOLIUMPROPYL P-PHENYLENEDIAMINE HCL (DESIGNATION A166)

CAS: 220158-86-1

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 28 endpoints
Source Endpoint Type Value Unit Species Route Duration Study Type Reference
SCCS Opinion NOAEL =0.0183 mg/kg rat oral developmental developmental toxicity {"dose":"Safety evaluation (including calculation of the MoS) CALCULATION OF THE MARGIN OF SAFETY (on-head concentrations of up to 2%) Absorption through the skin A = 1.89 μg/cm² Skin Area surface SAS = 580 cm2 Dermal absorption per treatment SAS x A x 0.001 = 1.10 mg Typical body weight of human bw = 60 kg Systemic exposure dose (SED) SAS x A x 0.001/bw...","effect":"_________________________________________________________________________________ 36 3.3.10. Human data / 3.3.11. Special investigations / 3.3.12. Safety evaluation (including calculation of the MoS) CALCULATION OF THE MARGIN OF SAFETY (on-head concentrations of up to 2%) Absorption through the skin A = 1.89 μg/cm² Skin Area surface SAS = 580 cm2 Dermal absorption per treatment SAS x A x 0.001 = 1.10 mg Typical body weight of human bw = 60 kg Systemic exposure dose (SED) SAS x A x 0.001/bw = 0.0183mg/kg No observed adverse effect level NOAELsys = 100 mg/kg bw/d (developmental toxicity, oral, rat) Bioavailability 50%* = 50 mg/kg bw/d Margin of Safety NOAELsys/SED = 2732 * standard procedure according to the SCCS's Notes of Guidance for the testing of cosmetic ingredients and their safety evaluation. 3.3.13. Discussion Physicochemical properties Impurities Physicochemical data indicate the presence of six impurities and five residual solvents. Considering MoS calculation based on added information provided by Applicant during the public co","page":36,"pdf":"sccs_o_231.pdf","row_type":"noael_study","study_id":"sccs_o_231_noael_008"}
SCCS Opinion NOAEL =0.0183 mg/kg rat oral developmental developmental toxicity {"dose":"Safety evaluation (including calculation of the MoS) CALCULATION OF THE MARGIN OF SAFETY (on-head concentrations of up to 2%) Absorption through the skin A = 1.89 μg/cm² Skin Area surface SAS = 580 cm2 Dermal absorption per treatment SAS x A x 0.001 = 1.10 mg Typical body weight of human bw = 60 kg Systemic exposure dose (SED) SAS x A x 0.001/bw...","effect":"_________________________________________________________________________________ 36 3.3.10. Human data / 3.3.11. Special investigations / 3.3.12. Safety evaluation (including calculation of the MoS) CALCULATION OF THE MARGIN OF SAFETY (on-head concentrations of up to 2%) Absorption through the skin A = 1.89 μg/cm² Skin Area surface SAS = 580 cm2 Dermal absorption per treatment SAS x A x 0.001 = 1.10 mg Typical body weight of human bw = 60 kg Systemic exposure dose (SED) SAS x A x 0.001/bw = 0.0183mg/kg No observed adverse effect level NOAELsys = 100 mg/kg bw/d (developmental toxicity, oral, rat) Bioavailability 50%* = 50 mg/kg bw/d Margin of Safety NOAELsys/SED = 2732 * standard procedure according to the SCCS's Notes of Guidance for the testing of cosmetic ingredients and their safety evaluation. 3.3.13. Discussion Physicochemical properties Impurities Physicochemical data indicate the presence of six impurities and five residual solvents. Considering MoS calculation based on added information provided by Applicant during the public co","page":36,"pdf":"sccs_o_231.pdf","row_type":"noael_study","study_id":"sccs_o_231_noael_008"}
SCCS Opinion NOAEL =0.0183 mg/kg rat oral developmental developmental toxicity {"dose":"Safety evaluation (including calculation of the MoS) CALCULATION OF THE MARGIN OF SAFETY (on-head concentrations of up to 2%) Absorption through the skin A = 1.89 μg/cm² Skin Area surface SAS = 580 cm2 Dermal absorption per treatment SAS x A x 0.001 = 1.10 mg Typical body weight of human bw = 60 kg Systemic exposure dose (SED) SAS x A x 0.001/bw...","effect":"_________________________________________________________________________________ 36 3.3.10. Human data / 3.3.11. Special investigations / 3.3.12. Safety evaluation (including calculation of the MoS) CALCULATION OF THE MARGIN OF SAFETY (on-head concentrations of up to 2%) Absorption through the skin A = 1.89 μg/cm² Skin Area surface SAS = 580 cm2 Dermal absorption per treatment SAS x A x 0.001 = 1.10 mg Typical body weight of human bw = 60 kg Systemic exposure dose (SED) SAS x A x 0.001/bw = 0.0183mg/kg No observed adverse effect level NOAELsys = 100 mg/kg bw/d (developmental toxicity, oral, rat) Bioavailability 50%* = 50 mg/kg bw/d Margin of Safety NOAELsys/SED = 2732 * standard procedure according to the SCCS's Notes of Guidance for the testing of cosmetic ingredients and their safety evaluation. 3.3.13. Discussion Physicochemical properties Impurities Physicochemical data indicate the presence of six impurities and five residual solvents. Considering MoS calculation based on added information provided by Applicant during the public co","page":36,"pdf":"sccs_o_231.pdf","row_type":"noael_study","study_id":"sccs_o_231_noael_008"}
SCCS Opinion NOAEL =0.0183 mg/kg rat oral developmental developmental toxicity {"dose":"Safety evaluation (including calculation of the MoS) CALCULATION OF THE MARGIN OF SAFETY (on-head concentrations of up to 2%) Absorption through the skin A = 1.89 μg/cm² Skin Area surface SAS = 580 cm2 Dermal absorption per treatment SAS x A x 0.001 = 1.10 mg Typical body weight of human bw = 60 kg Systemic exposure dose (SED) SAS x A x 0.001/bw...","effect":"_________________________________________________________________________________ 36 3.3.10. Human data / 3.3.11. Special investigations / 3.3.12. Safety evaluation (including calculation of the MoS) CALCULATION OF THE MARGIN OF SAFETY (on-head concentrations of up to 2%) Absorption through the skin A = 1.89 μg/cm² Skin Area surface SAS = 580 cm2 Dermal absorption per treatment SAS x A x 0.001 = 1.10 mg Typical body weight of human bw = 60 kg Systemic exposure dose (SED) SAS x A x 0.001/bw = 0.0183mg/kg No observed adverse effect level NOAELsys = 100 mg/kg bw/d (developmental toxicity, oral, rat) Bioavailability 50%* = 50 mg/kg bw/d Margin of Safety NOAELsys/SED = 2732 * standard procedure according to the SCCS's Notes of Guidance for the testing of cosmetic ingredients and their safety evaluation. 3.3.13. Discussion Physicochemical properties Impurities Physicochemical data indicate the presence of six impurities and five residual solvents. Considering MoS calculation based on added information provided by Applicant during the public co","page":36,"pdf":"sccs_o_231.pdf","row_type":"noael_study","study_id":"sccs_o_231_noael_008"}
SCCS Opinion NOAEL =100 mg/kg/day - - developmental developmental toxicity {"dose":"rmations and no skeletal findings in foetuses of treated animals.","effect":"rmations and no skeletal findings in foetuses of treated animals. Visceral examination indicated isolated gross lesions and were considered incidental by the study authors. Thus, there were no indications for a teratogenic potential. No significant changes in foetal parameters were observed at any dose level of Methylimidazoliumpropyl p-phenylenediamine, Cl, 2HCl (A166) when compared to the control group. Conclusion On the basis of the results obtained in the present study, the No Observed Adverse Effect Levels (NOAEL) for maternal and developmental toxicity of Methylimidazoliumpropyl p- phenylenediamine, Cl, 2HCl (A166) were set at 100 mg/kg/day and 1000 mg/kg/day,","page":29,"pdf":"sccs_o_231.pdf","row_type":"noael_study","study_id":"sccs_o_231_noael_005"}
SCCS Opinion NOAEL =100 mg/kg bw/d rat - developmental developmental toxicity {"citation":"Ref: Patel MV (2014) SCCS comment Methylimidazoliumpropyl phenylenediamine, Cl, 2HCl (A166) is not teratogenic in rats","dose":"A NOAEL of 1000 mg/kg bw/d is derived for developmental toxicity.","effect":"SCCS/1609/19 Final Opinion Opinion on hair dye Methylimidazoliumpropyl p-phenylenediamine HCl (A166) ___________________________________________________________________________________________ 30 respectively. Methylimidazoliumpropyl p-phenylenediamine, Cl, 2HCl (A166) was considered to have no teratogenic potential. Ref: Patel MV (2014) SCCS comment Methylimidazoliumpropyl phenylenediamine, Cl, 2HCl (A166) is not teratogenic in rats. A NOAEL of 1000 mg/kg bw/d is derived for developmental toxicity. A NOAEL of 100 mg/kg bw/d is derived for maternal toxicity due to changes in lethargy at 300 and 1000 mg/kg bw/d and weakness, hypoaesthesia and somnolence and decreased mean body weight gain and mean percent body weight and of absolute uterine weight and uterine weight corrected to body weight at 1000 mg/kg bw/d. 3.3.7 Mutagenicity / genotoxicity 3.3.7.1 Mutagenicity / genotoxicity in vitro Bacterial Reverse Mutation Assay Guideline: OECD 471 (1997) Species/Strain: Salmonella typhimurium TA1535, TA1537, TA98, TA100 a","page":30,"pdf":"sccs_o_231.pdf","row_type":"noael_study","study_id":"sccs_o_231_noael_007"}
SCCS Opinion NOAEL =100 mg/kg/day - - developmental developmental toxicity {"dose":"rmations and no skeletal findings in foetuses of treated animals.","effect":"rmations and no skeletal findings in foetuses of treated animals. Visceral examination indicated isolated gross lesions and were considered incidental by the study authors. Thus, there were no indications for a teratogenic potential. No significant changes in foetal parameters were observed at any dose level of Methylimidazoliumpropyl p-phenylenediamine, Cl, 2HCl (A166) when compared to the control group. Conclusion On the basis of the results obtained in the present study, the No Observed Adverse Effect Levels (NOAEL) for maternal and developmental toxicity of Methylimidazoliumpropyl p- phenylenediamine, Cl, 2HCl (A166) were set at 100 mg/kg/day and 1000 mg/kg/day,","page":29,"pdf":"sccs_o_231.pdf","row_type":"noael_study","study_id":"sccs_o_231_noael_005"}
SCCS Opinion NOAEL =100 mg/kg bw/d rat - developmental developmental toxicity {"citation":"Ref: Patel MV (2014) SCCS comment Methylimidazoliumpropyl phenylenediamine, Cl, 2HCl (A166) is not teratogenic in rats","dose":"A NOAEL of 1000 mg/kg bw/d is derived for developmental toxicity.","effect":"SCCS/1609/19 Final Opinion Opinion on hair dye Methylimidazoliumpropyl p-phenylenediamine HCl (A166) ___________________________________________________________________________________________ 30 respectively. Methylimidazoliumpropyl p-phenylenediamine, Cl, 2HCl (A166) was considered to have no teratogenic potential. Ref: Patel MV (2014) SCCS comment Methylimidazoliumpropyl phenylenediamine, Cl, 2HCl (A166) is not teratogenic in rats. A NOAEL of 1000 mg/kg bw/d is derived for developmental toxicity. A NOAEL of 100 mg/kg bw/d is derived for maternal toxicity due to changes in lethargy at 300 and 1000 mg/kg bw/d and weakness, hypoaesthesia and somnolence and decreased mean body weight gain and mean percent body weight and of absolute uterine weight and uterine weight corrected to body weight at 1000 mg/kg bw/d. 3.3.7 Mutagenicity / genotoxicity 3.3.7.1 Mutagenicity / genotoxicity in vitro Bacterial Reverse Mutation Assay Guideline: OECD 471 (1997) Species/Strain: Salmonella typhimurium TA1535, TA1537, TA98, TA100 a","page":30,"pdf":"sccs_o_231.pdf","row_type":"noael_study","study_id":"sccs_o_231_noael_007"}
SCCS Opinion NOAEL =100 mg/kg/day - - developmental developmental toxicity {"dose":"rmations and no skeletal findings in foetuses of treated animals.","effect":"rmations and no skeletal findings in foetuses of treated animals. Visceral examination indicated isolated gross lesions and were considered incidental by the study authors. Thus, there were no indications for a teratogenic potential. No significant changes in foetal parameters were observed at any dose level of Methylimidazoliumpropyl p-phenylenediamine, Cl, 2HCl (A166) when compared to the control group. Conclusion On the basis of the results obtained in the present study, the No Observed Adverse Effect Levels (NOAEL) for maternal and developmental toxicity of Methylimidazoliumpropyl p- phenylenediamine, Cl, 2HCl (A166) were set at 100 mg/kg/day and 1000 mg/kg/day,","page":29,"pdf":"sccs_o_231.pdf","row_type":"noael_study","study_id":"sccs_o_231_noael_005"}
SCCS Opinion NOAEL =100 mg/kg bw/d rat - developmental developmental toxicity {"citation":"Ref: Patel MV (2014) SCCS comment Methylimidazoliumpropyl phenylenediamine, Cl, 2HCl (A166) is not teratogenic in rats","dose":"A NOAEL of 1000 mg/kg bw/d is derived for developmental toxicity.","effect":"SCCS/1609/19 Final Opinion Opinion on hair dye Methylimidazoliumpropyl p-phenylenediamine HCl (A166) ___________________________________________________________________________________________ 30 respectively. Methylimidazoliumpropyl p-phenylenediamine, Cl, 2HCl (A166) was considered to have no teratogenic potential. Ref: Patel MV (2014) SCCS comment Methylimidazoliumpropyl phenylenediamine, Cl, 2HCl (A166) is not teratogenic in rats. A NOAEL of 1000 mg/kg bw/d is derived for developmental toxicity. A NOAEL of 100 mg/kg bw/d is derived for maternal toxicity due to changes in lethargy at 300 and 1000 mg/kg bw/d and weakness, hypoaesthesia and somnolence and decreased mean body weight gain and mean percent body weight and of absolute uterine weight and uterine weight corrected to body weight at 1000 mg/kg bw/d. 3.3.7 Mutagenicity / genotoxicity 3.3.7.1 Mutagenicity / genotoxicity in vitro Bacterial Reverse Mutation Assay Guideline: OECD 471 (1997) Species/Strain: Salmonella typhimurium TA1535, TA1537, TA98, TA100 a","page":30,"pdf":"sccs_o_231.pdf","row_type":"noael_study","study_id":"sccs_o_231_noael_007"}
SCCS Opinion NOAEL =100 mg/kg/day - - developmental developmental toxicity {"dose":"rmations and no skeletal findings in foetuses of treated animals.","effect":"rmations and no skeletal findings in foetuses of treated animals. Visceral examination indicated isolated gross lesions and were considered incidental by the study authors. Thus, there were no indications for a teratogenic potential. No significant changes in foetal parameters were observed at any dose level of Methylimidazoliumpropyl p-phenylenediamine, Cl, 2HCl (A166) when compared to the control group. Conclusion On the basis of the results obtained in the present study, the No Observed Adverse Effect Levels (NOAEL) for maternal and developmental toxicity of Methylimidazoliumpropyl p- phenylenediamine, Cl, 2HCl (A166) were set at 100 mg/kg/day and 1000 mg/kg/day,","page":29,"pdf":"sccs_o_231.pdf","row_type":"noael_study","study_id":"sccs_o_231_noael_005"}
SCCS Opinion NOAEL =100 mg/kg bw/d rat - developmental developmental toxicity {"citation":"Ref: Patel MV (2014) SCCS comment Methylimidazoliumpropyl phenylenediamine, Cl, 2HCl (A166) is not teratogenic in rats","dose":"A NOAEL of 1000 mg/kg bw/d is derived for developmental toxicity.","effect":"SCCS/1609/19 Final Opinion Opinion on hair dye Methylimidazoliumpropyl p-phenylenediamine HCl (A166) ___________________________________________________________________________________________ 30 respectively. Methylimidazoliumpropyl p-phenylenediamine, Cl, 2HCl (A166) was considered to have no teratogenic potential. Ref: Patel MV (2014) SCCS comment Methylimidazoliumpropyl phenylenediamine, Cl, 2HCl (A166) is not teratogenic in rats. A NOAEL of 1000 mg/kg bw/d is derived for developmental toxicity. A NOAEL of 100 mg/kg bw/d is derived for maternal toxicity due to changes in lethargy at 300 and 1000 mg/kg bw/d and weakness, hypoaesthesia and somnolence and decreased mean body weight gain and mean percent body weight and of absolute uterine weight and uterine weight corrected to body weight at 1000 mg/kg bw/d. 3.3.7 Mutagenicity / genotoxicity 3.3.7.1 Mutagenicity / genotoxicity in vitro Bacterial Reverse Mutation Assay Guideline: OECD 471 (1997) Species/Strain: Salmonella typhimurium TA1535, TA1537, TA98, TA100 a","page":30,"pdf":"sccs_o_231.pdf","row_type":"noael_study","study_id":"sccs_o_231_noael_007"}
SCCS Opinion NOAEL =200 mg/kg/day rat oral 28- day NOAEL study {"dose":"NOAEL value of 200 mg/kg/day (NOAEL obtained in the 28- day oral toxicity study in rats – OECD 407 (1999)), SCCS agrees on the fact that the presence of the impurity 3-aminopropyl imidazole at a maximum level of 0.1% in Methylimidazoliumpropyl p-phenylenediamine, Cl, 2HCl (A166) presents no or a negligible risk to human health.","effect":"_________________________ 14 Appendix 1, the Applicant has two assays conducted before and after the filtration of the sample, under the same chromatographic conditions showing that the % area of the main product and impurities are comparable in these two assays. SCCS underlines that Applicant should have clearly indicated which of the two assays have been conducted before or after filtration. Considering MoS calculation based on added information provided by Applicant during the public consultation period (i.e. NOAEL value of 200 mg/kg/day (NOAEL obtained in the 28- day oral toxicity study in rats – OECD 407 (1999)), SCCS agrees on the fact that the presence of the impurity 3-aminopropyl imidazole at a maximum level of 0.1% in Methylimidazoliumpropyl p-phenylenediamine, Cl, 2HCl (A166) presents no or a negligible risk to human health. Considering complementary information provided by Applicant during the public consultation period, the exposure to the impurity chloroethane to be considered is equal to 100 microgram per day wh","page":14,"pdf":"sccs_o_231.pdf","row_type":"noael_study","study_id":"sccs_o_231_noael_001"}
SCCS Opinion NOAEL =200 mg/kg/day rat oral 28- day NOAEL study {"dose":"NOAEL value of 200 mg/kg/day (NOAEL obtained in the 28- day oral toxicity study in rats – OECD 407 (1999)), SCCS agrees on the fact that the presence of the impurity 3-aminopropyl imidazole at a maximum level of 0.1% in Methylimidazoliumpropyl p-phenylenediamine, Cl, 2HCl (A166) presents no or a negligible risk to human health.","effect":"_________________________ 14 Appendix 1, the Applicant has two assays conducted before and after the filtration of the sample, under the same chromatographic conditions showing that the % area of the main product and impurities are comparable in these two assays. SCCS underlines that Applicant should have clearly indicated which of the two assays have been conducted before or after filtration. Considering MoS calculation based on added information provided by Applicant during the public consultation period (i.e. NOAEL value of 200 mg/kg/day (NOAEL obtained in the 28- day oral toxicity study in rats – OECD 407 (1999)), SCCS agrees on the fact that the presence of the impurity 3-aminopropyl imidazole at a maximum level of 0.1% in Methylimidazoliumpropyl p-phenylenediamine, Cl, 2HCl (A166) presents no or a negligible risk to human health. Considering complementary information provided by Applicant during the public consultation period, the exposure to the impurity chloroethane to be considered is equal to 100 microgram per day wh","page":14,"pdf":"sccs_o_231.pdf","row_type":"noael_study","study_id":"sccs_o_231_noael_001"}
SCCS Opinion NOAEL =200 mg/kg/day rat oral 28- day NOAEL study {"dose":"NOAEL value of 200 mg/kg/day (NOAEL obtained in the 28- day oral toxicity study in rats – OECD 407 (1999)), SCCS agrees on the fact that the presence of the impurity 3-aminopropyl imidazole at a maximum level of 0.1% in Methylimidazoliumpropyl p-phenylenediamine, Cl, 2HCl (A166) presents no or a negligible risk to human health.","effect":"_________________________ 14 Appendix 1, the Applicant has two assays conducted before and after the filtration of the sample, under the same chromatographic conditions showing that the % area of the main product and impurities are comparable in these two assays. SCCS underlines that Applicant should have clearly indicated which of the two assays have been conducted before or after filtration. Considering MoS calculation based on added information provided by Applicant during the public consultation period (i.e. NOAEL value of 200 mg/kg/day (NOAEL obtained in the 28- day oral toxicity study in rats – OECD 407 (1999)), SCCS agrees on the fact that the presence of the impurity 3-aminopropyl imidazole at a maximum level of 0.1% in Methylimidazoliumpropyl p-phenylenediamine, Cl, 2HCl (A166) presents no or a negligible risk to human health. Considering complementary information provided by Applicant during the public consultation period, the exposure to the impurity chloroethane to be considered is equal to 100 microgram per day wh","page":14,"pdf":"sccs_o_231.pdf","row_type":"noael_study","study_id":"sccs_o_231_noael_001"}
SCCS Opinion NOAEL =200 mg/kg/day rat oral 28- day NOAEL study {"dose":"NOAEL value of 200 mg/kg/day (NOAEL obtained in the 28- day oral toxicity study in rats – OECD 407 (1999)), SCCS agrees on the fact that the presence of the impurity 3-aminopropyl imidazole at a maximum level of 0.1% in Methylimidazoliumpropyl p-phenylenediamine, Cl, 2HCl (A166) presents no or a negligible risk to human health.","effect":"_________________________ 14 Appendix 1, the Applicant has two assays conducted before and after the filtration of the sample, under the same chromatographic conditions showing that the % area of the main product and impurities are comparable in these two assays. SCCS underlines that Applicant should have clearly indicated which of the two assays have been conducted before or after filtration. Considering MoS calculation based on added information provided by Applicant during the public consultation period (i.e. NOAEL value of 200 mg/kg/day (NOAEL obtained in the 28- day oral toxicity study in rats – OECD 407 (1999)), SCCS agrees on the fact that the presence of the impurity 3-aminopropyl imidazole at a maximum level of 0.1% in Methylimidazoliumpropyl p-phenylenediamine, Cl, 2HCl (A166) presents no or a negligible risk to human health. Considering complementary information provided by Applicant during the public consultation period, the exposure to the impurity chloroethane to be considered is equal to 100 microgram per day wh","page":14,"pdf":"sccs_o_231.pdf","row_type":"noael_study","study_id":"sccs_o_231_noael_001"}
SCCS Opinion NOAEL =300 mg/kg bw/d rat oral 90-day reproductive toxicity {"citation":"Ref: Gohel D (2014), Ujawane D (2013) SCCS comment Based on limited adverse effects (changes in clinical chemistry and haematology at the highest dose), the SCCS derives a NOAEL of 300","dose":"t 300 and 1000 mg/kg bw/d.","effect":"SCCS-rejected applicant NOAEL: t 300 and 1000 mg/kg bw/d. These effects were not considered treatment-related by the study authors. Conclusion Thus, under the conditions of the study, the NOEL (No Observed Effect Level) of this 90-day repeated oral toxicity study with Methylimidazoliumpropyl p-phenylenediamine, Cl, 2HCl (A166) in Wistar rats was defined at 300 mg/kg /day. Ref: Gohel D (2014), Ujawane D (2013) SCCS comment Based on limited adverse effects (changes in clinical chemistry and haematology at the highest dose), the SCCS derives a NOAEL of 300 mg/kg bw/d from this study. 3.3.5.3 Chronic (> 12 months) toxicity / 3.3.6. Reproductive toxicity 3.3.6.1 Fertility and reproduction toxicity / 3.3.6.2 Developmental Toxicity Guideline: OECD 414 (2001) Species/strain: Wistar rats Group size: 25 mated females per group Test substance: R0027494A, Methylimidazoliumpropyl p-phenylenediamine, Cl, 2HCl (A166) Batch: 009 D 003","page":28,"pdf":"sccs_o_231.pdf","row_type":"noael_study","study_id":"sccs_o_231_noael_004"}
SCCS Opinion NOAEL =300 mg/kg bw/d rat oral 90-day reproductive toxicity {"citation":"Ref: Gohel D (2014), Ujawane D (2013) SCCS comment Based on limited adverse effects (changes in clinical chemistry and haematology at the highest dose), the SCCS derives a NOAEL of 300","dose":"t 300 and 1000 mg/kg bw/d.","effect":"SCCS-rejected applicant NOAEL: t 300 and 1000 mg/kg bw/d. These effects were not considered treatment-related by the study authors. Conclusion Thus, under the conditions of the study, the NOEL (No Observed Effect Level) of this 90-day repeated oral toxicity study with Methylimidazoliumpropyl p-phenylenediamine, Cl, 2HCl (A166) in Wistar rats was defined at 300 mg/kg /day. Ref: Gohel D (2014), Ujawane D (2013) SCCS comment Based on limited adverse effects (changes in clinical chemistry and haematology at the highest dose), the SCCS derives a NOAEL of 300 mg/kg bw/d from this study. 3.3.5.3 Chronic (> 12 months) toxicity / 3.3.6. Reproductive toxicity 3.3.6.1 Fertility and reproduction toxicity / 3.3.6.2 Developmental Toxicity Guideline: OECD 414 (2001) Species/strain: Wistar rats Group size: 25 mated females per group Test substance: R0027494A, Methylimidazoliumpropyl p-phenylenediamine, Cl, 2HCl (A166) Batch: 009 D 003","page":28,"pdf":"sccs_o_231.pdf","row_type":"noael_study","study_id":"sccs_o_231_noael_004"}
SCCS Opinion NOAEL =300 mg/kg bw/d rat oral 90-day reproductive toxicity {"citation":"Ref: Gohel D (2014), Ujawane D (2013) SCCS comment Based on limited adverse effects (changes in clinical chemistry and haematology at the highest dose), the SCCS derives a NOAEL of 300","dose":"t 300 and 1000 mg/kg bw/d.","effect":"SCCS-rejected applicant NOAEL: t 300 and 1000 mg/kg bw/d. These effects were not considered treatment-related by the study authors. Conclusion Thus, under the conditions of the study, the NOEL (No Observed Effect Level) of this 90-day repeated oral toxicity study with Methylimidazoliumpropyl p-phenylenediamine, Cl, 2HCl (A166) in Wistar rats was defined at 300 mg/kg /day. Ref: Gohel D (2014), Ujawane D (2013) SCCS comment Based on limited adverse effects (changes in clinical chemistry and haematology at the highest dose), the SCCS derives a NOAEL of 300 mg/kg bw/d from this study. 3.3.5.3 Chronic (> 12 months) toxicity / 3.3.6. Reproductive toxicity 3.3.6.1 Fertility and reproduction toxicity / 3.3.6.2 Developmental Toxicity Guideline: OECD 414 (2001) Species/strain: Wistar rats Group size: 25 mated females per group Test substance: R0027494A, Methylimidazoliumpropyl p-phenylenediamine, Cl, 2HCl (A166) Batch: 009 D 003","page":28,"pdf":"sccs_o_231.pdf","row_type":"noael_study","study_id":"sccs_o_231_noael_004"}
SCCS Opinion NOAEL =300 mg/kg bw/d rat oral 90-day reproductive toxicity {"citation":"Ref: Gohel D (2014), Ujawane D (2013) SCCS comment Based on limited adverse effects (changes in clinical chemistry and haematology at the highest dose), the SCCS derives a NOAEL of 300","dose":"t 300 and 1000 mg/kg bw/d.","effect":"SCCS-rejected applicant NOAEL: t 300 and 1000 mg/kg bw/d. These effects were not considered treatment-related by the study authors. Conclusion Thus, under the conditions of the study, the NOEL (No Observed Effect Level) of this 90-day repeated oral toxicity study with Methylimidazoliumpropyl p-phenylenediamine, Cl, 2HCl (A166) in Wistar rats was defined at 300 mg/kg /day. Ref: Gohel D (2014), Ujawane D (2013) SCCS comment Based on limited adverse effects (changes in clinical chemistry and haematology at the highest dose), the SCCS derives a NOAEL of 300 mg/kg bw/d from this study. 3.3.5.3 Chronic (> 12 months) toxicity / 3.3.6. Reproductive toxicity 3.3.6.1 Fertility and reproduction toxicity / 3.3.6.2 Developmental Toxicity Guideline: OECD 414 (2001) Species/strain: Wistar rats Group size: 25 mated females per group Test substance: R0027494A, Methylimidazoliumpropyl p-phenylenediamine, Cl, 2HCl (A166) Batch: 009 D 003","page":28,"pdf":"sccs_o_231.pdf","row_type":"noael_study","study_id":"sccs_o_231_noael_004"}
SCCS Opinion NOAEL =1000 mg/kg bw/d rat oral 90-day reproductive toxicity {"citation":"Ref: Gohel D (2014), Ujawane D (2013) SCCS comment Based on limited adverse effects (changes in clinical chemistry and haematology at the highest dose), the SCCS derives a NOAEL of 300","dose":"Furthermore, haematology revealed significantly higher Hb, MCH and MCHA values and significantly lower APTT (Activated Partial Thromboplasin Time) and PT (prothrombin time) values in males at the highest dose and significantly lower PT values in females at 300 and 1000 mg/kg bw/d.","effect":"SCCS-rejected applicant NOAEL: ficantly higher blood AST concentrations and significantly lower blood sodium and chloride concentrations. Furthermore, haematology revealed significantly higher Hb, MCH and MCHA values and significantly lower APTT (Activated Partial Thromboplasin Time) and PT (prothrombin time) values in males at the highest dose and significantly lower PT values in females at 300 and 1000 mg/kg bw/d. These effects were not considered treatment-related by the study authors. Conclusion Thus, under the conditions of the study, the NOEL (No Observed Effect Level) of this 90-day repeated oral toxicity study with Methylimidazoliumpropyl p-phenylenediamine, Cl, 2HCl (A166) in Wistar rats was defined at 300 mg/kg /day. Ref: Gohel D (2014), Ujawane D (2013) SCCS comment Based on limited adverse effects (changes in clinical chemistry and haematology at the highest dose), the SCCS derives a NOAEL of 300 mg/kg bw/d from this study. 3.3.5.3 Chronic (> 12 months) toxicity / 3.3.6. Reproductive toxicity 3.3.6.1 Fertility and reproduction toxicity /","page":28,"pdf":"sccs_o_231.pdf","row_type":"noael_study","study_id":"sccs_o_231_noael_003"}
SCCS Opinion NOAEL =1000 mg/kg rat - developmental reproductive toxicity {"dose":"NOAEL for developmental toxicity is 1000 mg/kg b.w.","effect":"SCCS/1609/19 Final Opinion Opinion on hair dye Methylimidazoliumpropyl p-phenylenediamine HCl (A166) ___________________________________________________________________________________________ 38 Reproductive toxicity Methylimidazoliumpropyl phenylenediamine, Cl, 2HCl (A166) is not teratogenic in rats. NOAEL for developmental toxicity is 1000 mg/kg b.w. NOAEL for maternal toxicity is 100 mg/kg b.w. due to changes in lethargy at 300 and 1000 mg/kg b.w. and weakness, hypoaesthesia and sonnolence and decreased mean body weight gain and mean percent body weight and of absolute uterine weight and uterine weight corrected to body weight at 1000 mg/kg b.w. Mutagenicity / genotoxicity Based on the analysis of all the in vitro studies submitted, the SCCS considered Methylimidazoliumpropyl p-phenylenediamine, Cl, 2HCl (A166) a","page":38,"pdf":"sccs_o_231.pdf","row_type":"noael_study","study_id":"sccs_o_231_noael_012"}
SCCS Opinion NOAEL =1000 mg/kg bw/d rat oral 90-day reproductive toxicity {"citation":"Ref: Gohel D (2014), Ujawane D (2013) SCCS comment Based on limited adverse effects (changes in clinical chemistry and haematology at the highest dose), the SCCS derives a NOAEL of 300","dose":"Furthermore, haematology revealed significantly higher Hb, MCH and MCHA values and significantly lower APTT (Activated Partial Thromboplasin Time) and PT (prothrombin time) values in males at the highest dose and significantly lower PT values in females at 300 and 1000 mg/kg bw/d.","effect":"SCCS-rejected applicant NOAEL: ficantly higher blood AST concentrations and significantly lower blood sodium and chloride concentrations. Furthermore, haematology revealed significantly higher Hb, MCH and MCHA values and significantly lower APTT (Activated Partial Thromboplasin Time) and PT (prothrombin time) values in males at the highest dose and significantly lower PT values in females at 300 and 1000 mg/kg bw/d. These effects were not considered treatment-related by the study authors. Conclusion Thus, under the conditions of the study, the NOEL (No Observed Effect Level) of this 90-day repeated oral toxicity study with Methylimidazoliumpropyl p-phenylenediamine, Cl, 2HCl (A166) in Wistar rats was defined at 300 mg/kg /day. Ref: Gohel D (2014), Ujawane D (2013) SCCS comment Based on limited adverse effects (changes in clinical chemistry and haematology at the highest dose), the SCCS derives a NOAEL of 300 mg/kg bw/d from this study. 3.3.5.3 Chronic (> 12 months) toxicity / 3.3.6. Reproductive toxicity 3.3.6.1 Fertility and reproduction toxicity /","page":28,"pdf":"sccs_o_231.pdf","row_type":"noael_study","study_id":"sccs_o_231_noael_003"}
SCCS Opinion NOAEL =1000 mg/kg rat - developmental reproductive toxicity {"dose":"NOAEL for developmental toxicity is 1000 mg/kg b.w.","effect":"SCCS/1609/19 Final Opinion Opinion on hair dye Methylimidazoliumpropyl p-phenylenediamine HCl (A166) ___________________________________________________________________________________________ 38 Reproductive toxicity Methylimidazoliumpropyl phenylenediamine, Cl, 2HCl (A166) is not teratogenic in rats. NOAEL for developmental toxicity is 1000 mg/kg b.w. NOAEL for maternal toxicity is 100 mg/kg b.w. due to changes in lethargy at 300 and 1000 mg/kg b.w. and weakness, hypoaesthesia and sonnolence and decreased mean body weight gain and mean percent body weight and of absolute uterine weight and uterine weight corrected to body weight at 1000 mg/kg b.w. Mutagenicity / genotoxicity Based on the analysis of all the in vitro studies submitted, the SCCS considered Methylimidazoliumpropyl p-phenylenediamine, Cl, 2HCl (A166) a","page":38,"pdf":"sccs_o_231.pdf","row_type":"noael_study","study_id":"sccs_o_231_noael_012"}
SCCS Opinion NOAEL =1000 mg/kg bw/d rat oral 90-day reproductive toxicity {"citation":"Ref: Gohel D (2014), Ujawane D (2013) SCCS comment Based on limited adverse effects (changes in clinical chemistry and haematology at the highest dose), the SCCS derives a NOAEL of 300","dose":"Furthermore, haematology revealed significantly higher Hb, MCH and MCHA values and significantly lower APTT (Activated Partial Thromboplasin Time) and PT (prothrombin time) values in males at the highest dose and significantly lower PT values in females at 300 and 1000 mg/kg bw/d.","effect":"SCCS-rejected applicant NOAEL: ficantly higher blood AST concentrations and significantly lower blood sodium and chloride concentrations. Furthermore, haematology revealed significantly higher Hb, MCH and MCHA values and significantly lower APTT (Activated Partial Thromboplasin Time) and PT (prothrombin time) values in males at the highest dose and significantly lower PT values in females at 300 and 1000 mg/kg bw/d. These effects were not considered treatment-related by the study authors. Conclusion Thus, under the conditions of the study, the NOEL (No Observed Effect Level) of this 90-day repeated oral toxicity study with Methylimidazoliumpropyl p-phenylenediamine, Cl, 2HCl (A166) in Wistar rats was defined at 300 mg/kg /day. Ref: Gohel D (2014), Ujawane D (2013) SCCS comment Based on limited adverse effects (changes in clinical chemistry and haematology at the highest dose), the SCCS derives a NOAEL of 300 mg/kg bw/d from this study. 3.3.5.3 Chronic (> 12 months) toxicity / 3.3.6. Reproductive toxicity 3.3.6.1 Fertility and reproduction toxicity /","page":28,"pdf":"sccs_o_231.pdf","row_type":"noael_study","study_id":"sccs_o_231_noael_003"}
SCCS Opinion NOAEL =1000 mg/kg rat - developmental reproductive toxicity {"dose":"NOAEL for developmental toxicity is 1000 mg/kg b.w.","effect":"SCCS/1609/19 Final Opinion Opinion on hair dye Methylimidazoliumpropyl p-phenylenediamine HCl (A166) ___________________________________________________________________________________________ 38 Reproductive toxicity Methylimidazoliumpropyl phenylenediamine, Cl, 2HCl (A166) is not teratogenic in rats. NOAEL for developmental toxicity is 1000 mg/kg b.w. NOAEL for maternal toxicity is 100 mg/kg b.w. due to changes in lethargy at 300 and 1000 mg/kg b.w. and weakness, hypoaesthesia and sonnolence and decreased mean body weight gain and mean percent body weight and of absolute uterine weight and uterine weight corrected to body weight at 1000 mg/kg b.w. Mutagenicity / genotoxicity Based on the analysis of all the in vitro studies submitted, the SCCS considered Methylimidazoliumpropyl p-phenylenediamine, Cl, 2HCl (A166) a","page":38,"pdf":"sccs_o_231.pdf","row_type":"noael_study","study_id":"sccs_o_231_noael_012"}
SCCS Opinion NOAEL =1000 mg/kg bw/d rat oral 90-day reproductive toxicity {"citation":"Ref: Gohel D (2014), Ujawane D (2013) SCCS comment Based on limited adverse effects (changes in clinical chemistry and haematology at the highest dose), the SCCS derives a NOAEL of 300","dose":"Furthermore, haematology revealed significantly higher Hb, MCH and MCHA values and significantly lower APTT (Activated Partial Thromboplasin Time) and PT (prothrombin time) values in males at the highest dose and significantly lower PT values in females at 300 and 1000 mg/kg bw/d.","effect":"SCCS-rejected applicant NOAEL: ficantly higher blood AST concentrations and significantly lower blood sodium and chloride concentrations. Furthermore, haematology revealed significantly higher Hb, MCH and MCHA values and significantly lower APTT (Activated Partial Thromboplasin Time) and PT (prothrombin time) values in males at the highest dose and significantly lower PT values in females at 300 and 1000 mg/kg bw/d. These effects were not considered treatment-related by the study authors. Conclusion Thus, under the conditions of the study, the NOEL (No Observed Effect Level) of this 90-day repeated oral toxicity study with Methylimidazoliumpropyl p-phenylenediamine, Cl, 2HCl (A166) in Wistar rats was defined at 300 mg/kg /day. Ref: Gohel D (2014), Ujawane D (2013) SCCS comment Based on limited adverse effects (changes in clinical chemistry and haematology at the highest dose), the SCCS derives a NOAEL of 300 mg/kg bw/d from this study. 3.3.5.3 Chronic (> 12 months) toxicity / 3.3.6. Reproductive toxicity 3.3.6.1 Fertility and reproduction toxicity /","page":28,"pdf":"sccs_o_231.pdf","row_type":"noael_study","study_id":"sccs_o_231_noael_003"}
SCCS Opinion NOAEL =1000 mg/kg rat - developmental reproductive toxicity {"dose":"NOAEL for developmental toxicity is 1000 mg/kg b.w.","effect":"SCCS/1609/19 Final Opinion Opinion on hair dye Methylimidazoliumpropyl p-phenylenediamine HCl (A166) ___________________________________________________________________________________________ 38 Reproductive toxicity Methylimidazoliumpropyl phenylenediamine, Cl, 2HCl (A166) is not teratogenic in rats. NOAEL for developmental toxicity is 1000 mg/kg b.w. NOAEL for maternal toxicity is 100 mg/kg b.w. due to changes in lethargy at 300 and 1000 mg/kg b.w. and weakness, hypoaesthesia and sonnolence and decreased mean body weight gain and mean percent body weight and of absolute uterine weight and uterine weight corrected to body weight at 1000 mg/kg b.w. Mutagenicity / genotoxicity Based on the analysis of all the in vitro studies submitted, the SCCS considered Methylimidazoliumpropyl p-phenylenediamine, Cl, 2HCl (A166) a","page":38,"pdf":"sccs_o_231.pdf","row_type":"noael_study","study_id":"sccs_o_231_noael_012"}
Regulatory source 12 endpoints
Source Endpoint Type Value Unit Species Route Duration Study Type Reference
Regulatory source - 200 mg/kg/day rat oral 28- day - SOURCE_SUBDIR=sccs_o_231; REPORT_TITLE=Final Opinion Scientific Committee on Consumer Safety SCCS OPINION ON Hair dye Methylimidazoliumpropyl p-phenylenediamine HCl (A166) (CAS 220158-86-1); OPINION_NUMBER=SCCS/1609/19; COMMITTEE=Scientific Committee on Consumer Safety (SCCS); REPORT_DATE=adopted on 29 July 2019; VALUE_TEXT=200; DOSE=NOAEL value of 200 mg/kg/day (NOAEL obtained in the 28- day oral toxicity study in rats – OECD 407 (1999)), SCCS agrees on the fact that the presence of the impurity 3-aminopropyl imidazole at a maximum level of 0.1% in Methylimidazoliumpropyl p-phenylenediamine, Cl, 2HCl (A166) presents no or a negligible risk to human health.; EFFECT=_________________________ 14 Appendix 1, the Applicant has two assays conducted before and after the filtration of the sample, under the same chromatographic conditions showing that the % area of the main product and impurities are comparable in these two assays. SCCS underlines that Applicant should have clearly indicated which of the two assays have been conducted before or after filtration. Considering MoS calculation based on added information provided by Applicant during the public consultation period (i.e. NOAEL value of 200 mg/kg/day (NOAEL obtained in the 28- day oral toxicity study in rats – OECD 407 (1999)), SCCS agrees on the fact that the presence of the impurity 3-aminopropyl imidazole at a maximum level of 0.1% in Methylimidazoliumpropyl p-phenylenediamine, Cl, 2HCl (A166) presents no or a negligible risk to human health. Considering complementary information provided by Applicant during the public consultation period, the exposure to the impurity chloroethane to be considered is equal to 100 microgram per day wh; CITATION_NUMBERS=[]; DETAILS_JSON={"cas_number":"220158-86-1","citation":"","dose":"NOAEL value of 200 mg/kg/day (NOAEL obtained in the 28- day oral toxicity study in rats – OECD 407 (1999)), SCCS agrees on the fact that the presence of the impurity 3-aminopropyl imidazole at a maximum level of 0.1% in Methylimidazoliumpropyl p-phenylenediamine, Cl, 2HCl (A166) presents no or a negligible risk to human health.","duration":"28- day","effect":"_________________________ 14 Appendix 1, the Applicant has two assays conducted before and after the filtration of the sample, under the same chromatographic conditions showing that the % area of the main product and impurities are comparable in these two assays. SCCS underlines that Applicant should have clearly indicated which of the two assays have been conducted before or after filtration. Considering MoS calculation based on added information provided by Applicant during the public consultation period (i.e. NOAEL value of 200 mg/kg/day (NOAEL obtained in the 28- day oral toxicity study in rats – OECD 407 (1999)), SCCS agrees on the fact that the presence of the impurity 3-aminopropyl imidazole at a maximum level of 0.1% in Methylimidazoliumpropyl p-phenylenediamine, Cl, 2HCl (A166) presents no or a negligible risk to human health. Considering complementary information provided by Applicant during the public consultation period, the exposure to the impurity chloroethane to be considered is equal to 100 microgram per day wh","endpoint":"","ingredient":"Methylimidazoliumpropyl p-phenylenediamine HCl (A166)","loael_value":"","noael_unit":"mg/kg/day","noael_value":"200","page":14,"route":"oral","species":"rat","study_id":"sccs_o_231_noael_001"}
Regulatory source - 200 mg/kg/day rat oral 28- day - SOURCE_SUBDIR=sccs_o_231; REPORT_TITLE=Final Opinion Scientific Committee on Consumer Safety SCCS OPINION ON Hair dye Methylimidazoliumpropyl p-phenylenediamine HCl (A166) (CAS 220158-86-1); OPINION_NUMBER=SCCS/1609/19; COMMITTEE=Scientific Committee on Consumer Safety (SCCS); REPORT_DATE=adopted on 29 July 2019; VALUE_TEXT=200; DOSE=NOAEL value of 200 mg/kg/day (NOAEL obtained in the 28- day oral toxicity study in rats – OECD 407 (1999)), SCCS agrees on the fact that the presence of the impurity 3-aminopropyl imidazole at a maximum level of 0.1% in Methylimidazoliumpropyl p-phenylenediamine, Cl, 2HCl (A166) presents no or a negligible risk to human health.; EFFECT=Appendix 1, the Applicant has two assays conducted before and after the filtration of the sample, under the same chromatographic conditions showing that the % area of the main product and impurities are comparable in these two assays. SCCS underlines that Applicant should have clearly indicated which of the two assays have been conducted before or after filtration. Considering MoS calculation based on added information provided by Applicant during the public consultation period (i.e. NOAEL value of 200 mg/kg/day (NOAEL obtained in the 28- day oral toxicity study in rats – OECD 407 (1999)), SCCS agrees on the fact that the presence of the impurity 3-aminopropyl imidazole at a maximum level of 0.1% in Methylimidazoliumpropyl p-phenylenediamine, Cl, 2HCl (A166) presents no or a negligible risk to human health. Considering complementary information provided by Applicant during the public consultation period, the exposure to the impurity chloroethane to be considered is equal to 100 microgram per day which is below the NSRL of 150 m; CITATION_NUMBERS=[]; DETAILS_JSON={"cas_number":"220158-86-1","citation":"","dose":"NOAEL value of 200 mg/kg/day (NOAEL obtained in the 28- day oral toxicity study in rats – OECD 407 (1999)), SCCS agrees on the fact that the presence of the impurity 3-aminopropyl imidazole at a maximum level of 0.1% in Methylimidazoliumpropyl p-phenylenediamine, Cl, 2HCl (A166) presents no or a negligible risk to human health.","duration":"28- day","effect":"Appendix 1, the Applicant has two assays conducted before and after the filtration of the sample, under the same chromatographic conditions showing that the % area of the main product and impurities are comparable in these two assays. SCCS underlines that Applicant should have clearly indicated which of the two assays have been conducted before or after filtration. Considering MoS calculation based on added information provided by Applicant during the public consultation period (i.e. NOAEL value of 200 mg/kg/day (NOAEL obtained in the 28- day oral toxicity study in rats – OECD 407 (1999)), SCCS agrees on the fact that the presence of the impurity 3-aminopropyl imidazole at a maximum level of 0.1% in Methylimidazoliumpropyl p-phenylenediamine, Cl, 2HCl (A166) presents no or a negligible risk to human health. Considering complementary information provided by Applicant during the public consultation period, the exposure to the impurity chloroethane to be considered is equal to 100 microgram per day which is below the NSRL of 150 m","endpoint":"","ingredient":"Methylimidazoliumpropyl p-phenylenediamine HCl (A166)","loael_value":"","noael_unit":"mg/kg/day","noael_value":"200","page":14,"route":"oral","species":"rat","study_id":"sccs_o_231_noael_002"}
Regulatory source - 200 mg/kg/day rat oral 28- day - SOURCE_SUBDIR=sccs_o_231; REPORT_TITLE=Final Opinion Scientific Committee on Consumer Safety SCCS OPINION ON Hair dye Methylimidazoliumpropyl p-phenylenediamine HCl (A166) (CAS 220158-86-1); OPINION_NUMBER=SCCS/1609/19; COMMITTEE=Scientific Committee on Consumer Safety (SCCS); REPORT_DATE=adopted on 29 July 2019; VALUE_TEXT=200; DOSE=al, rat) Bioavailability 50%* = 50 mg/kg bw/d Margin of Safety NOAELsys/SED = 2732 * standard procedure according to the SCCS's Notes of Guidance for the testing of cosmetic ingredients and their safety evaluation.; EFFECT=al, rat) Bioavailability 50%* = 50 mg/kg bw/d Margin of Safety NOAELsys/SED = 2732 * standard procedure according to the SCCS's Notes of Guidance for the testing of cosmetic ingredients and their safety evaluation. 3.3.13. Discussion Physicochemical properties Impurities Physicochemical data indicate the presence of six impurities and five residual solvents. Considering MoS calculation based on added information provided by Applicant during the public consultation period (i.e. NOAEL value of 200 mg/kg/day (NOAEL obtained in the 28- day oral toxicity study in rats – OECD 407 (1999)), SCCS agrees on the fact tha the presence of the impurity 3-aminopropyl imidazole at a maximum level of 0.1% in Methylimidazoliumpropyl p-phenylenediamine, Cl, 2HCl (A166) presents no or a negligible risk to human health. Considering complementary information provided by Applicant during the public consultation period, the exposure to the impurity chloroethane to be considered is equal to 100 microgram per day which is below the NSRL of 150 mi; CITATION_NUMBERS=[]; DETAILS_JSON={"cas_number":"220158-86-1","citation":"","dose":"al, rat) Bioavailability 50%* = 50 mg/kg bw/d Margin of Safety NOAELsys/SED = 2732 * standard procedure according to the SCCS's Notes of Guidance for the testing of cosmetic ingredients and their safety evaluation.","duration":"28- day","effect":"al, rat) Bioavailability 50%* = 50 mg/kg bw/d Margin of Safety NOAELsys/SED = 2732 * standard procedure according to the SCCS's Notes of Guidance for the testing of cosmetic ingredients and their safety evaluation. 3.3.13. Discussion Physicochemical properties Impurities Physicochemical data indicate the presence of six impurities and five residual solvents. Considering MoS calculation based on added information provided by Applicant during the public consultation period (i.e. NOAEL value of 200 mg/kg/day (NOAEL obtained in the 28- day oral toxicity study in rats – OECD 407 (1999)), SCCS agrees on the fact tha the presence of the impurity 3-aminopropyl imidazole at a maximum level of 0.1% in Methylimidazoliumpropyl p-phenylenediamine, Cl, 2HCl (A166) presents no or a negligible risk to human health. Considering complementary information provided by Applicant during the public consultation period, the exposure to the impurity chloroethane to be considered is equal to 100 microgram per day which is below the NSRL of 150 mi","endpoint":"","ingredient":"Methylimidazoliumpropyl p-phenylenediamine HCl (A166)","loael_value":"","noael_unit":"mg/kg/day","noael_value":"200","page":36,"route":"oral","species":"rat","study_id":"sccs_o_231_noael_010"}
Regulatory source developmental toxicity =0.0183 mg/kg rat oral developmental developmental toxicity SOURCE_SUBDIR=sccs_o_231; REPORT_TITLE=Final Opinion Scientific Committee on Consumer Safety SCCS OPINION ON Hair dye Methylimidazoliumpropyl p-phenylenediamine HCl (A166) (CAS 220158-86-1); OPINION_NUMBER=SCCS/1609/19; COMMITTEE=Scientific Committee on Consumer Safety (SCCS); REPORT_DATE=adopted on 29 July 2019; VALUE_TEXT== 0.0183; DOSE=Safety evaluation (including calculation of the MoS) CALCULATION OF THE MARGIN OF SAFETY (on-head concentrations of up to 2%) Absorption through the skin A = 1.89 μg/cm² Skin Area surface SAS = 580 cm2 Dermal absorption per treatment SAS x A x 0.001 = 1.10 mg Typical body weight of human bw = 60 kg Systemic exposure dose (SED) SAS x A x 0.001/bw...; EFFECT=_________________________________________________________________________________ 36 3.3.10. Human data / 3.3.11. Special investigations / 3.3.12. Safety evaluation (including calculation of the MoS) CALCULATION OF THE MARGIN OF SAFETY (on-head concentrations of up to 2%) Absorption through the skin A = 1.89 μg/cm² Skin Area surface SAS = 580 cm2 Dermal absorption per treatment SAS x A x 0.001 = 1.10 mg Typical body weight of human bw = 60 kg Systemic exposure dose (SED) SAS x A x 0.001/bw = 0.0183mg/kg No observed adverse effect level NOAELsys = 100 mg/kg bw/d (developmental toxicity, oral, rat) Bioavailability 50%* = 50 mg/kg bw/d Margin of Safety NOAELsys/SED = 2732 * standard procedure according to the SCCS's Notes of Guidance for the testing of cosmetic ingredients and their safety evaluation. 3.3.13. Discussion Physicochemical properties Impurities Physicochemical data indicate the presence of six impurities and five residual solvents. Considering MoS calculation based on added information provided by Applicant during the public co; CITATION_NUMBERS=[]; DETAILS_JSON={"cas_number":"220158-86-1","citation":"","dose":"Safety evaluation (including calculation of the MoS) CALCULATION OF THE MARGIN OF SAFETY (on-head concentrations of up to 2%) Absorption through the skin A = 1.89 μg/cm² Skin Area surface SAS = 580 cm2 Dermal absorption per treatment SAS x A x 0.001 = 1.10 mg Typical body weight of human bw = 60 kg Systemic exposure dose (SED) SAS x A x 0.001/bw...","duration":"developmental","effect":"_________________________________________________________________________________ 36 3.3.10. Human data / 3.3.11. Special investigations / 3.3.12. Safety evaluation (including calculation of the MoS) CALCULATION OF THE MARGIN OF SAFETY (on-head concentrations of up to 2%) Absorption through the skin A = 1.89 μg/cm² Skin Area surface SAS = 580 cm2 Dermal absorption per treatment SAS x A x 0.001 = 1.10 mg Typical body weight of human bw = 60 kg Systemic exposure dose (SED) SAS x A x 0.001/bw = 0.0183mg/kg No observed adverse effect level NOAELsys = 100 mg/kg bw/d (developmental toxicity, oral, rat) Bioavailability 50%* = 50 mg/kg bw/d Margin of Safety NOAELsys/SED = 2732 * standard procedure according to the SCCS's Notes of Guidance for the testing of cosmetic ingredients and their safety evaluation. 3.3.13. Discussion Physicochemical properties Impurities Physicochemical data indicate the presence of six impurities and five residual solvents. Considering MoS calculation based on added information provided by Applicant during the public co","endpoint":"developmental toxicity","ingredient":"Methylimidazoliumpropyl p-phenylenediamine HCl (A166)","loael_value":"","noael_unit":"mg/kg","noael_value":"= 0.0183","page":36,"route":"oral","species":"rat","study_id":"sccs_o_231_noael_008"}
Regulatory source developmental toxicity 100 mg/kg/day - - developmental developmental toxicity SOURCE_SUBDIR=sccs_o_231; REPORT_TITLE=Final Opinion Scientific Committee on Consumer Safety SCCS OPINION ON Hair dye Methylimidazoliumpropyl p-phenylenediamine HCl (A166) (CAS 220158-86-1); OPINION_NUMBER=SCCS/1609/19; COMMITTEE=Scientific Committee on Consumer Safety (SCCS); REPORT_DATE=adopted on 29 July 2019; VALUE_TEXT=100; DOSE=rmations and no skeletal findings in foetuses of treated animals.; EFFECT=rmations and no skeletal findings in foetuses of treated animals. Visceral examination indicated isolated gross lesions and were considered incidental by the study authors. Thus, there were no indications for a teratogenic potential. No significant changes in foetal parameters were observed at any dose level of Methylimidazoliumpropyl p-phenylenediamine, Cl, 2HCl (A166) when compared to the control group. Conclusion On the basis of the results obtained in the present study, the No Observed Adverse Effect Levels (NOAEL) for maternal and developmental toxicity of Methylimidazoliumpropyl p- phenylenediamine, Cl, 2HCl (A166) were set at 100 mg/kg/day and 1000 mg/kg/day,; CITATION_NUMBERS=[]; DETAILS_JSON={"cas_number":"220158-86-1","citation":"","dose":"rmations and no skeletal findings in foetuses of treated animals.","duration":"developmental","effect":"rmations and no skeletal findings in foetuses of treated animals. Visceral examination indicated isolated gross lesions and were considered incidental by the study authors. Thus, there were no indications for a teratogenic potential. No significant changes in foetal parameters were observed at any dose level of Methylimidazoliumpropyl p-phenylenediamine, Cl, 2HCl (A166) when compared to the control group. Conclusion On the basis of the results obtained in the present study, the No Observed Adverse Effect Levels (NOAEL) for maternal and developmental toxicity of Methylimidazoliumpropyl p- phenylenediamine, Cl, 2HCl (A166) were set at 100 mg/kg/day and 1000 mg/kg/day,","endpoint":"developmental toxicity","ingredient":"Methylimidazoliumpropyl p-phenylenediamine HCl (A166)","loael_value":"","noael_unit":"mg/kg/day","noael_value":"100","page":29,"route":"","species":"","study_id":"sccs_o_231_noael_005"}
Regulatory source developmental toxicity 100 mg/kg bw/d rat - developmental developmental toxicity SOURCE_SUBDIR=sccs_o_231; REPORT_TITLE=Final Opinion Scientific Committee on Consumer Safety SCCS OPINION ON Hair dye Methylimidazoliumpropyl p-phenylenediamine HCl (A166) (CAS 220158-86-1); OPINION_NUMBER=SCCS/1609/19; COMMITTEE=Scientific Committee on Consumer Safety (SCCS); REPORT_DATE=adopted on 29 July 2019; VALUE_TEXT=100; DOSE=A NOAEL of 1000 mg/kg bw/d is derived for developmental toxicity.; EFFECT=SCCS/1609/19 Final Opinion Opinion on hair dye Methylimidazoliumpropyl p-phenylenediamine HCl (A166) ___________________________________________________________________________________________ 30 respectively. Methylimidazoliumpropyl p-phenylenediamine, Cl, 2HCl (A166) was considered to have no teratogenic potential. Ref: Patel MV (2014) SCCS comment Methylimidazoliumpropyl phenylenediamine, Cl, 2HCl (A166) is not teratogenic in rats. A NOAEL of 1000 mg/kg bw/d is derived for developmental toxicity. A NOAEL of 100 mg/kg bw/d is derived for maternal toxicity due to changes in lethargy at 300 and 1000 mg/kg bw/d and weakness, hypoaesthesia and somnolence and decreased mean body weight gain and mean percent body weight and of absolute uterine weight and uterine weight corrected to body weight at 1000 mg/kg bw/d. 3.3.7 Mutagenicity / genotoxicity 3.3.7.1 Mutagenicity / genotoxicity in vitro Bacterial Reverse Mutation Assay Guideline: OECD 471 (1997) Species/Strain: Salmonella typhimurium TA1535, TA1537, TA98, TA100 a; CITATION=Ref: Patel MV (2014) SCCS comment Methylimidazoliumpropyl phenylenediamine, Cl, 2HCl (A166) is not teratogenic in rats; CITATION_NUMBERS=[2014,2,166]; REFERENCE=Ref: Patel MV (2014) SCCS comment Methylimidazoliumpropyl phenylenediamine, Cl, 2HCl (A166) is not teratogenic in rats; DETAILS_JSON={"cas_number":"220158-86-1","citation":"Ref: Patel MV (2014) SCCS comment Methylimidazoliumpropyl phenylenediamine, Cl, 2HCl (A166) is not teratogenic in rats","dose":"A NOAEL of 1000 mg/kg bw/d is derived for developmental toxicity.","duration":"developmental","effect":"SCCS/1609/19 Final Opinion Opinion on hair dye Methylimidazoliumpropyl p-phenylenediamine HCl (A166) ___________________________________________________________________________________________ 30 respectively. Methylimidazoliumpropyl p-phenylenediamine, Cl, 2HCl (A166) was considered to have no teratogenic potential. Ref: Patel MV (2014) SCCS comment Methylimidazoliumpropyl phenylenediamine, Cl, 2HCl (A166) is not teratogenic in rats. A NOAEL of 1000 mg/kg bw/d is derived for developmental toxicity. A NOAEL of 100 mg/kg bw/d is derived for maternal toxicity due to changes in lethargy at 300 and 1000 mg/kg bw/d and weakness, hypoaesthesia and somnolence and decreased mean body weight gain and mean percent body weight and of absolute uterine weight and uterine weight corrected to body weight at 1000 mg/kg bw/d. 3.3.7 Mutagenicity / genotoxicity 3.3.7.1 Mutagenicity / genotoxicity in vitro Bacterial Reverse Mutation Assay Guideline: OECD 471 (1997) Species/Strain: Salmonella typhimurium TA1535, TA1537, TA98, TA100 a","endpoint":"developmental toxicity","ingredient":"Methylimidazoliumpropyl p-phenylenediamine HCl (A166)","loael_value":"","noael_unit":"mg/kg bw/d","noael_value":"100","page":30,"route":"","species":"rat","study_id":"sccs_o_231_noael_007"}
Regulatory source developmental toxicity 200 mg/kg/day rat oral developmental developmental toxicity SOURCE_SUBDIR=sccs_o_231; REPORT_TITLE=Final Opinion Scientific Committee on Consumer Safety SCCS OPINION ON Hair dye Methylimidazoliumpropyl p-phenylenediamine HCl (A166) (CAS 220158-86-1); OPINION_NUMBER=SCCS/1609/19; COMMITTEE=Scientific Committee on Consumer Safety (SCCS); REPORT_DATE=adopted on 29 July 2019; VALUE_TEXT=200; DOSE=/d (developmental toxicity, oral, rat) Bioavailability 50%* = 50 mg/kg bw/d Margin of Safety NOAELsys/SED = 2732 * standard procedure according to the SCCS's Notes of Guidance for the testing of cosmetic ingredients and their safety evaluation.; EFFECT=/d (developmental toxicity, oral, rat) Bioavailability 50%* = 50 mg/kg bw/d Margin of Safety NOAELsys/SED = 2732 * standard procedure according to the SCCS's Notes of Guidance for the testing of cosmetic ingredients and their safety evaluation. 3.3.13. Discussion Physicochemical properties Impurities Physicochemical data indicate the presence of six impurities and five residual solvents. Considering MoS calculation based on added information provided by Applicant during the public consultation period (i.e. NOAEL value of 200 mg/kg/day (NOAEL obtained in the 28- day oral toxicity study in rats – OECD 407 (1999)), SCCS agrees on the fact tha the presence of the impurity 3-aminopropyl imidazole at a maximum level of 0.1% in Methylimidazoliumpropyl p-phenylenediamine, Cl, 2HCl (A166) presents no or a negligible risk to human health. Considering complementary information provided by Applicant during the public consultation period, the exposure to the impurity chloroethane to be considered is equal to 100 microgram per day whi; CITATION_NUMBERS=[]; DETAILS_JSON={"cas_number":"220158-86-1","citation":"","dose":"/d (developmental toxicity, oral, rat) Bioavailability 50%* = 50 mg/kg bw/d Margin of Safety NOAELsys/SED = 2732 * standard procedure according to the SCCS's Notes of Guidance for the testing of cosmetic ingredients and their safety evaluation.","duration":"developmental","effect":"/d (developmental toxicity, oral, rat) Bioavailability 50%* = 50 mg/kg bw/d Margin of Safety NOAELsys/SED = 2732 * standard procedure according to the SCCS's Notes of Guidance for the testing of cosmetic ingredients and their safety evaluation. 3.3.13. Discussion Physicochemical properties Impurities Physicochemical data indicate the presence of six impurities and five residual solvents. Considering MoS calculation based on added information provided by Applicant during the public consultation period (i.e. NOAEL value of 200 mg/kg/day (NOAEL obtained in the 28- day oral toxicity study in rats – OECD 407 (1999)), SCCS agrees on the fact tha the presence of the impurity 3-aminopropyl imidazole at a maximum level of 0.1% in Methylimidazoliumpropyl p-phenylenediamine, Cl, 2HCl (A166) presents no or a negligible risk to human health. Considering complementary information provided by Applicant during the public consultation period, the exposure to the impurity chloroethane to be considered is equal to 100 microgram per day whi","endpoint":"developmental toxicity","ingredient":"Methylimidazoliumpropyl p-phenylenediamine HCl (A166)","loael_value":"","noael_unit":"mg/kg/day","noael_value":"200","page":36,"route":"oral","species":"rat","study_id":"sccs_o_231_noael_009"}
Regulatory source developmental toxicity 1000 mg/kg bw/d rat - developmental developmental toxicity SOURCE_SUBDIR=sccs_o_231; REPORT_TITLE=Final Opinion Scientific Committee on Consumer Safety SCCS OPINION ON Hair dye Methylimidazoliumpropyl p-phenylenediamine HCl (A166) (CAS 220158-86-1); OPINION_NUMBER=SCCS/1609/19; COMMITTEE=Scientific Committee on Consumer Safety (SCCS); REPORT_DATE=adopted on 29 July 2019; VALUE_TEXT=1000; DOSE=A NOAEL of 1000 mg/kg bw/d is derived for developmental toxicity.; EFFECT=SCCS/1609/19 Final Opinion Opinion on hair dye Methylimidazoliumpropyl p-phenylenediamine HCl (A166) ___________________________________________________________________________________________ 30 respectively. Methylimidazoliumpropyl p-phenylenediamine, Cl, 2HCl (A166) was considered to have no teratogenic potential. Ref: Patel MV (2014) SCCS comment Methylimidazoliumpropyl phenylenediamine, Cl, 2HCl (A166) is not teratogenic in rats. A NOAEL of 1000 mg/kg bw/d is derived for developmental toxicity. A NOAEL of 100 mg/kg bw/d is derived for maternal toxicity due to changes in lethargy at 300 and 1000 mg/kg bw/d and weakness, hypoaesthesia and somnolence and decreased mean body weight gain and mean percent body weight and of absolute uterine weight and uterine weight corrected to body weight at 1000 mg/kg bw/d. 3.3.7 Mutagenicity / genotoxicity 3.3.7.1 Mutagenicity / genotoxicity in vitro Bacterial Reverse Mutation Assay Guideline: OECD 471 (1997) S; CITATION=Ref: Patel MV (2014) SCCS comment Methylimidazoliumpropyl phenylenediamine, Cl, 2HCl (A166) is not teratogenic in rats; CITATION_NUMBERS=[2014,2,166]; REFERENCE=Ref: Patel MV (2014) SCCS comment Methylimidazoliumpropyl phenylenediamine, Cl, 2HCl (A166) is not teratogenic in rats; DETAILS_JSON={"cas_number":"220158-86-1","citation":"Ref: Patel MV (2014) SCCS comment Methylimidazoliumpropyl phenylenediamine, Cl, 2HCl (A166) is not teratogenic in rats","dose":"A NOAEL of 1000 mg/kg bw/d is derived for developmental toxicity.","duration":"developmental","effect":"SCCS/1609/19 Final Opinion Opinion on hair dye Methylimidazoliumpropyl p-phenylenediamine HCl (A166) ___________________________________________________________________________________________ 30 respectively. Methylimidazoliumpropyl p-phenylenediamine, Cl, 2HCl (A166) was considered to have no teratogenic potential. Ref: Patel MV (2014) SCCS comment Methylimidazoliumpropyl phenylenediamine, Cl, 2HCl (A166) is not teratogenic in rats. A NOAEL of 1000 mg/kg bw/d is derived for developmental toxicity. A NOAEL of 100 mg/kg bw/d is derived for maternal toxicity due to changes in lethargy at 300 and 1000 mg/kg bw/d and weakness, hypoaesthesia and somnolence and decreased mean body weight gain and mean percent body weight and of absolute uterine weight and uterine weight corrected to body weight at 1000 mg/kg bw/d. 3.3.7 Mutagenicity / genotoxicity 3.3.7.1 Mutagenicity / genotoxicity in vitro Bacterial Reverse Mutation Assay Guideline: OECD 471 (1997) S","endpoint":"developmental toxicity","ingredient":"Methylimidazoliumpropyl p-phenylenediamine HCl (A166)","loael_value":"","noael_unit":"mg/kg bw/d","noael_value":"1000","page":30,"route":"","species":"rat","study_id":"sccs_o_231_noael_006"}
Regulatory source repeated dose toxicity 300 mg/kg bw/d rat oral 90-day repeated dose toxicity SOURCE_SUBDIR=sccs_o_231; REPORT_TITLE=Final Opinion Scientific Committee on Consumer Safety SCCS OPINION ON Hair dye Methylimidazoliumpropyl p-phenylenediamine HCl (A166) (CAS 220158-86-1); OPINION_NUMBER=SCCS/1609/19; COMMITTEE=Scientific Committee on Consumer Safety (SCCS); REPORT_DATE=adopted on 29 July 2019; VALUE_TEXT=300; DOSE=Repeated dose toxicity Based on limited adverse effects (changes in clinical chemistry and haematology at the highest dose) observed after Repeated dose 90-day oral toxicity study of Methylimidazoliumpropyl p-phenylenediamine, Cl, 2HCl (A166) in wistar rats, the SCCS derives a NOAEL of 300 mg/kg bw/d.; EFFECT=rmal absorption value, i.e. 1.89 µg/cm2 (0.48%), will be used for MoS calculation. A moderate permeability observed in this study supports the default value of 50% for oral bioavailability, which will be used for the calculation of the MoS. Repeated dose toxicity Based on limited adverse effects (changes in clinical chemistry and haematology at the highest dose) observed after Repeated dose 90-day oral toxicity study of Methylimidazoliumpropyl p-phenylenediamine, Cl, 2HCl (A166) in wistar rats, the SCCS derives a NOAEL of 300 mg/kg bw/d.; CITATION_NUMBERS=[]; DETAILS_JSON={"cas_number":"220158-86-1","citation":"","dose":"Repeated dose toxicity Based on limited adverse effects (changes in clinical chemistry and haematology at the highest dose) observed after Repeated dose 90-day oral toxicity study of Methylimidazoliumpropyl p-phenylenediamine, Cl, 2HCl (A166) in wistar rats, the SCCS derives a NOAEL of 300 mg/kg bw/d.","duration":"90-day","effect":"rmal absorption value, i.e. 1.89 µg/cm2 (0.48%), will be used for MoS calculation. A moderate permeability observed in this study supports the default value of 50% for oral bioavailability, which will be used for the calculation of the MoS. Repeated dose toxicity Based on limited adverse effects (changes in clinical chemistry and haematology at the highest dose) observed after Repeated dose 90-day oral toxicity study of Methylimidazoliumpropyl p-phenylenediamine, Cl, 2HCl (A166) in wistar rats, the SCCS derives a NOAEL of 300 mg/kg bw/d.","endpoint":"repeated dose toxicity","ingredient":"Methylimidazoliumpropyl p-phenylenediamine HCl (A166)","loael_value":"","noael_unit":"mg/kg bw/d","noael_value":"300","page":37,"route":"oral","species":"rat","study_id":"sccs_o_231_noael_011"}
Regulatory source reproductive toxicity 300 mg/kg bw/d rat oral 90-day reproductive toxicity SOURCE_SUBDIR=sccs_o_231; REPORT_TITLE=Final Opinion Scientific Committee on Consumer Safety SCCS OPINION ON Hair dye Methylimidazoliumpropyl p-phenylenediamine HCl (A166) (CAS 220158-86-1); OPINION_NUMBER=SCCS/1609/19; COMMITTEE=Scientific Committee on Consumer Safety (SCCS); REPORT_DATE=adopted on 29 July 2019; VALUE_TEXT=300; DOSE=t 300 and 1000 mg/kg bw/d.; EFFECT=SCCS-rejected applicant NOAEL: t 300 and 1000 mg/kg bw/d. These effects were not considered treatment-related by the study authors. Conclusion Thus, under the conditions of the study, the NOEL (No Observed Effect Level) of this 90-day repeated oral toxicity study with Methylimidazoliumpropyl p-phenylenediamine, Cl, 2HCl (A166) in Wistar rats was defined at 300 mg/kg /day. Ref: Gohel D (2014), Ujawane D (2013) SCCS comment Based on limited adverse effects (changes in clinical chemistry and haematology at the highest dose), the SCCS derives a NOAEL of 300 mg/kg bw/d from this study. 3.3.5.3 Chronic (> 12 months) toxicity / 3.3.6. Reproductive toxicity 3.3.6.1 Fertility and reproduction toxicity / 3.3.6.2 Developmental Toxicity Guideline: OECD 414 (2001) Species/strain: Wistar rats Group size: 25 mated females per group Test substance: R0027494A, Methylimidazoliumpropyl p-phenylenediamine, Cl, 2HCl (A166) Batch: 009 D 003; CITATION=Ref: Gohel D (2014), Ujawane D (2013) SCCS comment Based on limited adverse effects (changes in clinical chemistry and haematology at the highest dose), the SCCS derives a NOAEL of 300; CITATION_NUMBERS=[2014,2013,300]; REFERENCE=Ref: Gohel D (2014), Ujawane D (2013) SCCS comment Based on limited adverse effects (changes in clinical chemistry and haematology at the highest dose), the SCCS derives a NOAEL of 300; DETAILS_JSON={"cas_number":"220158-86-1","citation":"Ref: Gohel D (2014), Ujawane D (2013) SCCS comment Based on limited adverse effects (changes in clinical chemistry and haematology at the highest dose), the SCCS derives a NOAEL of 300","dose":"t 300 and 1000 mg/kg bw/d.","duration":"90-day","effect":"SCCS-rejected applicant NOAEL: t 300 and 1000 mg/kg bw/d. These effects were not considered treatment-related by the study authors. Conclusion Thus, under the conditions of the study, the NOEL (No Observed Effect Level) of this 90-day repeated oral toxicity study with Methylimidazoliumpropyl p-phenylenediamine, Cl, 2HCl (A166) in Wistar rats was defined at 300 mg/kg /day. Ref: Gohel D (2014), Ujawane D (2013) SCCS comment Based on limited adverse effects (changes in clinical chemistry and haematology at the highest dose), the SCCS derives a NOAEL of 300 mg/kg bw/d from this study. 3.3.5.3 Chronic (> 12 months) toxicity / 3.3.6. Reproductive toxicity 3.3.6.1 Fertility and reproduction toxicity / 3.3.6.2 Developmental Toxicity Guideline: OECD 414 (2001) Species/strain: Wistar rats Group size: 25 mated females per group Test substance: R0027494A, Methylimidazoliumpropyl p-phenylenediamine, Cl, 2HCl (A166) Batch: 009 D 003","endpoint":"reproductive toxicity","ingredient":"Methylimidazoliumpropyl p-phenylenediamine HCl (A166)","loael_value":"","noael_unit":"mg/kg bw/d","noael_value":"300","page":28,"route":"oral","species":"rat","study_id":"sccs_o_231_noael_004"}
Regulatory source reproductive toxicity 1000 mg/kg bw/d rat oral 90-day reproductive toxicity SOURCE_SUBDIR=sccs_o_231; REPORT_TITLE=Final Opinion Scientific Committee on Consumer Safety SCCS OPINION ON Hair dye Methylimidazoliumpropyl p-phenylenediamine HCl (A166) (CAS 220158-86-1); OPINION_NUMBER=SCCS/1609/19; COMMITTEE=Scientific Committee on Consumer Safety (SCCS); REPORT_DATE=adopted on 29 July 2019; VALUE_TEXT=1000; DOSE=Furthermore, haematology revealed significantly higher Hb, MCH and MCHA values and significantly lower APTT (Activated Partial Thromboplasin Time) and PT (prothrombin time) values in males at the highest dose and significantly lower PT values in females at 300 and 1000 mg/kg bw/d.; EFFECT=SCCS-rejected applicant NOAEL: ficantly higher blood AST concentrations and significantly lower blood sodium and chloride concentrations. Furthermore, haematology revealed significantly higher Hb, MCH and MCHA values and significantly lower APTT (Activated Partial Thromboplasin Time) and PT (prothrombin time) values in males at the highest dose and significantly lower PT values in females at 300 and 1000 mg/kg bw/d. These effects were not considered treatment-related by the study authors. Conclusion Thus, under the conditions of the study, the NOEL (No Observed Effect Level) of this 90-day repeated oral toxicity study with Methylimidazoliumpropyl p-phenylenediamine, Cl, 2HCl (A166) in Wistar rats was defined at 300 mg/kg /day. Ref: Gohel D (2014), Ujawane D (2013) SCCS comment Based on limited adverse effects (changes in clinical chemistry and haematology at the highest dose), the SCCS derives a NOAEL of 300 mg/kg bw/d from this study. 3.3.5.3 Chronic (> 12 months) toxicity / 3.3.6. Reproductive toxicity 3.3.6.1 Fertility and reproduction toxicity /; CITATION=Ref: Gohel D (2014), Ujawane D (2013) SCCS comment Based on limited adverse effects (changes in clinical chemistry and haematology at the highest dose), the SCCS derives a NOAEL of 300; CITATION_NUMBERS=[2014,2013,300]; REFERENCE=Ref: Gohel D (2014), Ujawane D (2013) SCCS comment Based on limited adverse effects (changes in clinical chemistry and haematology at the highest dose), the SCCS derives a NOAEL of 300; DETAILS_JSON={"cas_number":"220158-86-1","citation":"Ref: Gohel D (2014), Ujawane D (2013) SCCS comment Based on limited adverse effects (changes in clinical chemistry and haematology at the highest dose), the SCCS derives a NOAEL of 300","dose":"Furthermore, haematology revealed significantly higher Hb, MCH and MCHA values and significantly lower APTT (Activated Partial Thromboplasin Time) and PT (prothrombin time) values in males at the highest dose and significantly lower PT values in females at 300 and 1000 mg/kg bw/d.","duration":"90-day","effect":"SCCS-rejected applicant NOAEL: ficantly higher blood AST concentrations and significantly lower blood sodium and chloride concentrations. Furthermore, haematology revealed significantly higher Hb, MCH and MCHA values and significantly lower APTT (Activated Partial Thromboplasin Time) and PT (prothrombin time) values in males at the highest dose and significantly lower PT values in females at 300 and 1000 mg/kg bw/d. These effects were not considered treatment-related by the study authors. Conclusion Thus, under the conditions of the study, the NOEL (No Observed Effect Level) of this 90-day repeated oral toxicity study with Methylimidazoliumpropyl p-phenylenediamine, Cl, 2HCl (A166) in Wistar rats was defined at 300 mg/kg /day. Ref: Gohel D (2014), Ujawane D (2013) SCCS comment Based on limited adverse effects (changes in clinical chemistry and haematology at the highest dose), the SCCS derives a NOAEL of 300 mg/kg bw/d from this study. 3.3.5.3 Chronic (> 12 months) toxicity / 3.3.6. Reproductive toxicity 3.3.6.1 Fertility and reproduction toxicity /","endpoint":"reproductive toxicity","ingredient":"Methylimidazoliumpropyl p-phenylenediamine HCl (A166)","loael_value":"","noael_unit":"mg/kg bw/d","noael_value":"1000","page":28,"route":"oral","species":"rat","study_id":"sccs_o_231_noael_003"}
Regulatory source reproductive toxicity 1000 mg/kg rat - developmental reproductive toxicity SOURCE_SUBDIR=sccs_o_231; REPORT_TITLE=Final Opinion Scientific Committee on Consumer Safety SCCS OPINION ON Hair dye Methylimidazoliumpropyl p-phenylenediamine HCl (A166) (CAS 220158-86-1); OPINION_NUMBER=SCCS/1609/19; COMMITTEE=Scientific Committee on Consumer Safety (SCCS); REPORT_DATE=adopted on 29 July 2019; VALUE_TEXT=1000; DOSE=NOAEL for developmental toxicity is 1000 mg/kg b.w.; EFFECT=SCCS/1609/19 Final Opinion Opinion on hair dye Methylimidazoliumpropyl p-phenylenediamine HCl (A166) ___________________________________________________________________________________________ 38 Reproductive toxicity Methylimidazoliumpropyl phenylenediamine, Cl, 2HCl (A166) is not teratogenic in rats. NOAEL for developmental toxicity is 1000 mg/kg b.w. NOAEL for maternal toxicity is 100 mg/kg b.w. due to changes in lethargy at 300 and 1000 mg/kg b.w. and weakness, hypoaesthesia and sonnolence and decreased mean body weight gain and mean percent body weight and of absolute uterine weight and uterine weight corrected to body weight at 1000 mg/kg b.w. Mutagenicity / genotoxicity Based on the analysis of all the in vitro studies submitted, the SCCS considered Methylimidazoliumpropyl p-phenylenediamine, Cl, 2HCl (A166) a; CITATION_NUMBERS=[]; DETAILS_JSON={"cas_number":"220158-86-1","citation":"","dose":"NOAEL for developmental toxicity is 1000 mg/kg b.w.","duration":"developmental","effect":"SCCS/1609/19 Final Opinion Opinion on hair dye Methylimidazoliumpropyl p-phenylenediamine HCl (A166) ___________________________________________________________________________________________ 38 Reproductive toxicity Methylimidazoliumpropyl phenylenediamine, Cl, 2HCl (A166) is not teratogenic in rats. NOAEL for developmental toxicity is 1000 mg/kg b.w. NOAEL for maternal toxicity is 100 mg/kg b.w. due to changes in lethargy at 300 and 1000 mg/kg b.w. and weakness, hypoaesthesia and sonnolence and decreased mean body weight gain and mean percent body weight and of absolute uterine weight and uterine weight corrected to body weight at 1000 mg/kg b.w. Mutagenicity / genotoxicity Based on the analysis of all the in vitro studies submitted, the SCCS considered Methylimidazoliumpropyl p-phenylenediamine, Cl, 2HCl (A166) a","endpoint":"reproductive toxicity","ingredient":"Methylimidazoliumpropyl p-phenylenediamine HCl (A166)","loael_value":"","noael_unit":"mg/kg","noael_value":"1000","page":38,"route":"","species":"rat","study_id":"sccs_o_231_noael_012"}