s from temporary tattoos and clothing textiles. PPD is an extreme, s................................................................... 98, Methylene Bis-Benzotriazolyl Tetramethylbutylphenol (nano)

SOURCE_SUBDIR=sccs_o_094; REPORT_TITLE=OPINION ON p-Phenylenediamine COLIPA n° A7; OPINION_NUMBER=SCCS/1443/11; COMMITTEE=Scientific Committee on Consumer Safety (SCCS); REPORT_DATE=18 September 2012; VALUE_TEXT=1; DOSE=Margins of exposure (MOE) derived based on the systemic exposure of rats treated with PPD in toxicity studies and humans exposed to hair dyes providing either 2% or 1% PPD on head.; EFFECT=s PPD equivalents (ng-eq/g*h) using the data from the recent study of Meuling and de Bie (Ref. 14, subm. V) in which 1% PPD was applied on head. Margins of exposure (MOE) derived based on the systemic exposure of rats treated with PPD in toxicity studies and humans exposed to hair dyes providing either 2% or 1% PPD on head. Dose in rats (mg/kg bw) AUC0-infinity in rats (based on data from 4 mg/kg bw kinetic study) AUC0-infinity in humans (2% on head) MOE AUC0-infinity in humans (1% on head) MOE Gavage dose of 4 (NOAEL used by the SCCP) 11076 1415 7.8 966 11.5 Gavage NOAEL of 8 22152 1415 15.6 966 22.2 Gavage NOAEL of 16 44304 1415 31.3 966 45.9 Dietary NOEL of 50 138450 1415 97.8 966 143.3 AUC0-infinity in rats (based on data from 6.45 mg/kg bw kinetic study) AUC0-infinity in humans (2% on head) MOE AUC0-infinity in humans (1% on head) MOE Gavage dose of 4 (NOAEL used by the SCCP) 16519 1415 11.6 966 17.1 Gavage NOAEL of 8 33038 1415 23.3 966 34.2 Gavage NOAEL of 16 66076 1415 46.7 966 68.4 Dietary NOEL of 50 206488 1415 145.9; CITATION=(Ref. 14, subm. V); CITATION_NUMBERS=[14]; REFERENCE=(Ref. 14, subm. V); DETAILS_JSON={"cas_number":"106-50-3","citation":"(Ref. 14, subm. V)","dose":"Margins of exposure (MOE) derived based on the systemic exposure of rats treated with PPD in toxicity studies and humans exposed to hair dyes providing either 2% or 1% PPD on head.","duration":"","effect":"s PPD equivalents (ng-eq/g*h) using the data from the recent study of Meuling and de Bie (Ref. 14, subm. V) in which 1% PPD was applied on head. Margins of exposure (MOE) derived based on the systemic exposure of rats treated with PPD in toxicity studies and humans exposed to hair dyes providing either 2% or 1% PPD on head. Dose in rats (mg/kg bw) AUC0-infinity in rats (based on data from 4 mg/kg bw kinetic study) AUC0-infinity in humans (2% on head) MOE AUC0-infinity in humans (1% on head) MOE Gavage dose of 4 (NOAEL used by the SCCP) 11076 1415 7.8 966 11.5 Gavage NOAEL of 8 22152 1415 15.6 966 22.2 Gavage NOAEL of 16 44304 1415 31.3 966 45.9 Dietary NOEL of 50 138450 1415 97.8 966 143.3 AUC0-infinity in rats (based on data from 6.45 mg/kg bw kinetic study) AUC0-infinity in humans (2% on head) MOE AUC0-infinity in humans (1% on head) MOE Gavage dose of 4 (NOAEL used by the SCCP) 16519 1415 11.6 966 17.1 Gavage NOAEL of 8 33038 1415 23.3 966 34.2 Gavage NOAEL of 16 66076 1415 46.7 966 68.4 Dietary NOEL of 50 206488 1415 145.9","endpoint":"","ingredient":"s from temporary tattoos and clothing textiles. PPD is an extreme","loael_value":"","noael_unit":"%","noael_value":"1","page":61,"route":"oral","species":"rat","study_id":"sccs_o_094_noael_027"}

sccs_o_094.pdf

SOURCE_SUBDIR=sccs_o_094; REPORT_TITLE=OPINION ON p-Phenylenediamine COLIPA n° A7; OPINION_NUMBER=SCCS/1443/11; COMMITTEE=Scientific Committee on Consumer Safety (SCCS); REPORT_DATE=18 September 2012; VALUE_TEXT=1; DOSE=Margins of exposure (MOE) derived based on the systemic exposure of rats treated with PPD in toxicity studies and humans exposed to hair dyes providing either 2% or 1% PPD on head.; EFFECT=ecent study of Meuling and de Bie (Ref. 14, subm. V) in which 1% PPD was applied on head. Margins of exposure (MOE) derived based on the systemic exposure of rats treated with PPD in toxicity studies and humans exposed to hair dyes providing either 2% or 1% PPD on head. Dose in rats (mg/kg bw) AUC0-infinity in rats (based on data from 4 mg/kg bw kinetic study) AUC0-infinity in humans (2% on head) MOE AUC0-infinity in humans (1% on head) MOE Gavage dose of 4 (NOAEL used by the SCCP) 11076 1415 7.8 966 11.5 Gavage NOAEL of 8 22152 1415 15.6 966 22.2 Gavage NOAEL of 16 44304 1415 31.3 966 45.9 Dietary NOEL of 50 138450 1415 97.8 966 143.3 AUC0-infinity in rats (based on data from 6.45 mg/kg bw kinetic study) AUC0-infinity in humans (2% on head) MOE AUC0-infinity in humans (1% on head) MOE Gavage dose of 4 (NOAEL used by the SCCP) 16519 1415 11.6 966 17.1 Gavage NOAEL of 8 33038 1415 23.3 966 34.2 Gavage NOAEL of 16 66076 1415 46.7 966 68.4 Dietary NOEL of 50 206488 1415 145.9 966 213.8; CITATION=(Ref. 14, subm. V); CITATION_NUMBERS=[14]; REFERENCE=(Ref. 14, subm. V); DETAILS_JSON={"cas_number":"106-50-3","citation":"(Ref. 14, subm. V)","dose":"Margins of exposure (MOE) derived based on the systemic exposure of rats treated with PPD in toxicity studies and humans exposed to hair dyes providing either 2% or 1% PPD on head.","duration":"","effect":"ecent study of Meuling and de Bie (Ref. 14, subm. V) in which 1% PPD was applied on head. Margins of exposure (MOE) derived based on the systemic exposure of rats treated with PPD in toxicity studies and humans exposed to hair dyes providing either 2% or 1% PPD on head. Dose in rats (mg/kg bw) AUC0-infinity in rats (based on data from 4 mg/kg bw kinetic study) AUC0-infinity in humans (2% on head) MOE AUC0-infinity in humans (1% on head) MOE Gavage dose of 4 (NOAEL used by the SCCP) 11076 1415 7.8 966 11.5 Gavage NOAEL of 8 22152 1415 15.6 966 22.2 Gavage NOAEL of 16 44304 1415 31.3 966 45.9 Dietary NOEL of 50 138450 1415 97.8 966 143.3 AUC0-infinity in rats (based on data from 6.45 mg/kg bw kinetic study) AUC0-infinity in humans (2% on head) MOE AUC0-infinity in humans (1% on head) MOE Gavage dose of 4 (NOAEL used by the SCCP) 16519 1415 11.6 966 17.1 Gavage NOAEL of 8 33038 1415 23.3 966 34.2 Gavage NOAEL of 16 66076 1415 46.7 966 68.4 Dietary NOEL of 50 206488 1415 145.9 966 213.8","endpoint":"","ingredient":"s from temporary tattoos and clothing textiles. PPD is an extreme","loael_value":"","noael_unit":"%","noael_value":"1","page":61,"route":"oral","species":"rat","study_id":"sccs_o_094_noael_028"}

sccs_o_094.pdf

SOURCE_SUBDIR=sccs_o_094; REPORT_TITLE=OPINION ON p-Phenylenediamine COLIPA n° A7; OPINION_NUMBER=SCCS/1443/11; COMMITTEE=Scientific Committee on Consumer Safety (SCCS); REPORT_DATE=18 September 2012; VALUE_TEXT=1; DOSE=UC0-infinity in rats (based on data from 4 mg/kg bw kinetic study) AUC0-infinity in humans (2% on head) MOE AUC0-infinity in humans (1% on head) MOE Gavage dose of 4 (NOAEL used by the SCCP) 11076 1415 7.8 966 11.5 Gavage NOAEL of 8 22152 1415 15.6 966 22.2 Gavage NOAEL of 16 44304 1415 31.3 966 45.9 Dietary NOEL of 50 138450 1415 97.8 966 143.3...; EFFECT=UC0-infinity in rats (based on data from 4 mg/kg bw kinetic study) AUC0-infinity in humans (2% on head) MOE AUC0-infinity in humans (1% on head) MOE Gavage dose of 4 (NOAEL used by the SCCP) 11076 1415 7.8 966 11.5 Gavage NOAEL of 8 22152 1415 15.6 966 22.2 Gavage NOAEL of 16 44304 1415 31.3 966 45.9 Dietary NOEL of 50 138450 1415 97.8 966 143.3 AUC0-infinity in rats (based on data from 6.45 mg/kg bw kinetic study) AUC0-infinity in humans (2% on head) MOE AUC0-infinity in humans (1% on head) MOE Gavage dose of 4 (NOAEL used by the SCCP) 16519 1415 11.6 966 17.1 Gavage NOAEL of 8 33038 1415 23.3 966 34.2 Gavage NOAEL of 16 66076 1415 46.7 966 68.4 Dietary NOEL of 50 206488 1415 145.9 966 213.8; CITATION_NUMBERS=[]; DETAILS_JSON={"cas_number":"106-50-3","citation":"","dose":"UC0-infinity in rats (based on data from 4 mg/kg bw kinetic study) AUC0-infinity in humans (2% on head) MOE AUC0-infinity in humans (1% on head) MOE Gavage dose of 4 (NOAEL used by the SCCP) 11076 1415 7.8 966 11.5 Gavage NOAEL of 8 22152 1415 15.6 966 22.2 Gavage NOAEL of 16 44304 1415 31.3 966 45.9 Dietary NOEL of 50 138450 1415 97.8 966 143.3...","duration":"","effect":"UC0-infinity in rats (based on data from 4 mg/kg bw kinetic study) AUC0-infinity in humans (2% on head) MOE AUC0-infinity in humans (1% on head) MOE Gavage dose of 4 (NOAEL used by the SCCP) 11076 1415 7.8 966 11.5 Gavage NOAEL of 8 22152 1415 15.6 966 22.2 Gavage NOAEL of 16 44304 1415 31.3 966 45.9 Dietary NOEL of 50 138450 1415 97.8 966 143.3 AUC0-infinity in rats (based on data from 6.45 mg/kg bw kinetic study) AUC0-infinity in humans (2% on head) MOE AUC0-infinity in humans (1% on head) MOE Gavage dose of 4 (NOAEL used by the SCCP) 16519 1415 11.6 966 17.1 Gavage NOAEL of 8 33038 1415 23.3 966 34.2 Gavage NOAEL of 16 66076 1415 46.7 966 68.4 Dietary NOEL of 50 206488 1415 145.9 966 213.8","endpoint":"","ingredient":"s from temporary tattoos and clothing textiles. PPD is an extreme","loael_value":"","noael_unit":"%","noael_value":"1","page":61,"route":"oral","species":"rat","study_id":"sccs_o_094_noael_031"}

sccs_o_094.pdf

SOURCE_SUBDIR=sccs_o_094; REPORT_TITLE=OPINION ON p-Phenylenediamine COLIPA n° A7; OPINION_NUMBER=SCCS/1443/11; COMMITTEE=Scientific Committee on Consumer Safety (SCCS); REPORT_DATE=18 September 2012; VALUE_TEXT=1; DOSE=tic study) AUC0-infinity in humans (2% on head) MOE AUC0-infinity in humans (1% on head) MOE Gavage dose of 4 (NOAEL used by the SCCP) 11076 1415 7.8 966 11.5 Gavage NOAEL of 8 22152 1415 15.6 966 22.2 Gavage NOAEL of 16 44304 1415 31.3 966 45.9 Dietary NOEL of 50 138450 1415 97.8 966 143.3 AUC0-infinity in rats (based on data from 6.45 mg/kg bw...; EFFECT=tic study) AUC0-infinity in humans (2% on head) MOE AUC0-infinity in humans (1% on head) MOE Gavage dose of 4 (NOAEL used by the SCCP) 11076 1415 7.8 966 11.5 Gavage NOAEL of 8 22152 1415 15.6 966 22.2 Gavage NOAEL of 16 44304 1415 31.3 966 45.9 Dietary NOEL of 50 138450 1415 97.8 966 143.3 AUC0-infinity in rats (based on data from 6.45 mg/kg bw kinetic study) AUC0-infinity in humans (2% on head) MOE AUC0-infinity in humans (1% on head) MOE Gavage dose of 4 (NOAEL used by the SCCP) 16519 1415 11.6 966 17.1 Gavage NOAEL of 8 33038 1415 23.3 966 34.2 Gavage NOAEL of 16 66076 1415 46.7 966 68.4 Dietary NOEL of 50 206488 1415 145.9 966 213.8; CITATION_NUMBERS=[]; DETAILS_JSON={"cas_number":"106-50-3","citation":"","dose":"tic study) AUC0-infinity in humans (2% on head) MOE AUC0-infinity in humans (1% on head) MOE Gavage dose of 4 (NOAEL used by the SCCP) 11076 1415 7.8 966 11.5 Gavage NOAEL of 8 22152 1415 15.6 966 22.2 Gavage NOAEL of 16 44304 1415 31.3 966 45.9 Dietary NOEL of 50 138450 1415 97.8 966 143.3 AUC0-infinity in rats (based on data from 6.45 mg/kg bw...","duration":"","effect":"tic study) AUC0-infinity in humans (2% on head) MOE AUC0-infinity in humans (1% on head) MOE Gavage dose of 4 (NOAEL used by the SCCP) 11076 1415 7.8 966 11.5 Gavage NOAEL of 8 22152 1415 15.6 966 22.2 Gavage NOAEL of 16 44304 1415 31.3 966 45.9 Dietary NOEL of 50 138450 1415 97.8 966 143.3 AUC0-infinity in rats (based on data from 6.45 mg/kg bw kinetic study) AUC0-infinity in humans (2% on head) MOE AUC0-infinity in humans (1% on head) MOE Gavage dose of 4 (NOAEL used by the SCCP) 16519 1415 11.6 966 17.1 Gavage NOAEL of 8 33038 1415 23.3 966 34.2 Gavage NOAEL of 16 66076 1415 46.7 966 68.4 Dietary NOEL of 50 206488 1415 145.9 966 213.8","endpoint":"","ingredient":"s from temporary tattoos and clothing textiles. PPD is an extreme","loael_value":"","noael_unit":"%","noael_value":"1","page":61,"route":"oral","species":"rat","study_id":"sccs_o_094_noael_032"}

sccs_o_094.pdf

SOURCE_SUBDIR=sccs_o_094; REPORT_TITLE=OPINION ON p-Phenylenediamine COLIPA n° A7; OPINION_NUMBER=SCCS/1443/11; COMMITTEE=Scientific Committee on Consumer Safety (SCCS); REPORT_DATE=18 September 2012; VALUE_TEXT=1; DOSE=ead) MOE AUC0-infinity in humans (1% on head) MOE Gavage dose of 4 (NOAEL used by the SCCP) 11076 1415 7.8 966 11.5 Gavage NOAEL of 8 22152 1415 15.6 966 22.2 Gavage NOAEL of 16 44304 1415 31.3 966 45.9 Dietary NOEL of 50 138450 1415 97.8 966 143.3 AUC0-infinity in rats (based on data from 6.45 mg/kg bw kinetic study) AUC0-infinity in humans (2%...; EFFECT=ead) MOE AUC0-infinity in humans (1% on head) MOE Gavage dose of 4 (NOAEL used by the SCCP) 11076 1415 7.8 966 11.5 Gavage NOAEL of 8 22152 1415 15.6 966 22.2 Gavage NOAEL of 16 44304 1415 31.3 966 45.9 Dietary NOEL of 50 138450 1415 97.8 966 143.3 AUC0-infinity in rats (based on data from 6.45 mg/kg bw kinetic study) AUC0-infinity in humans (2% on head) MOE AUC0-infinity in humans (1% on head) MOE Gavage dose of 4 (NOAEL used by the SCCP) 16519 1415 11.6 966 17.1 Gavage NOAEL of 8 33038 1415 23.3 966 34.2 Gavage NOAEL of 16 66076 1415 46.7 966 68.4 Dietary NOEL of 50 206488 1415 145.9 966 213.8; CITATION_NUMBERS=[]; DETAILS_JSON={"cas_number":"106-50-3","citation":"","dose":"ead) MOE AUC0-infinity in humans (1% on head) MOE Gavage dose of 4 (NOAEL used by the SCCP) 11076 1415 7.8 966 11.5 Gavage NOAEL of 8 22152 1415 15.6 966 22.2 Gavage NOAEL of 16 44304 1415 31.3 966 45.9 Dietary NOEL of 50 138450 1415 97.8 966 143.3 AUC0-infinity in rats (based on data from 6.45 mg/kg bw kinetic study) AUC0-infinity in humans (2%...","duration":"","effect":"ead) MOE AUC0-infinity in humans (1% on head) MOE Gavage dose of 4 (NOAEL used by the SCCP) 11076 1415 7.8 966 11.5 Gavage NOAEL of 8 22152 1415 15.6 966 22.2 Gavage NOAEL of 16 44304 1415 31.3 966 45.9 Dietary NOEL of 50 138450 1415 97.8 966 143.3 AUC0-infinity in rats (based on data from 6.45 mg/kg bw kinetic study) AUC0-infinity in humans (2% on head) MOE AUC0-infinity in humans (1% on head) MOE Gavage dose of 4 (NOAEL used by the SCCP) 16519 1415 11.6 966 17.1 Gavage NOAEL of 8 33038 1415 23.3 966 34.2 Gavage NOAEL of 16 66076 1415 46.7 966 68.4 Dietary NOEL of 50 206488 1415 145.9 966 213.8","endpoint":"","ingredient":"s from temporary tattoos and clothing textiles. PPD is an extreme","loael_value":"","noael_unit":"%","noael_value":"1","page":61,"route":"oral","species":"rat","study_id":"sccs_o_094_noael_033"}

sccs_o_094.pdf

SOURCE_SUBDIR=sccs_o_094; REPORT_TITLE=OPINION ON p-Phenylenediamine COLIPA n° A7; OPINION_NUMBER=SCCS/1443/11; COMMITTEE=Scientific Committee on Consumer Safety (SCCS); REPORT_DATE=18 September 2012; VALUE_TEXT=1; DOSE=MOE Gavage dose of 4 (NOAEL used by the SCCP) 11076 1415 7.8 966 11.5 Gavage NOAEL of 8 22152 1415 15.6 966 22.2 Gavage NOAEL of 16 44304 1415 31.3 966 45.9 Dietary NOEL of 50 138450 1415 97.8 966 143.3 AUC0-infinity in rats (based on data from 6.45 mg/kg bw kinetic study) AUC0-infinity in humans (2% on head) MOE AUC0-infinity in humans (1% on h...; EFFECT=MOE Gavage dose of 4 (NOAEL used by the SCCP) 11076 1415 7.8 966 11.5 Gavage NOAEL of 8 22152 1415 15.6 966 22.2 Gavage NOAEL of 16 44304 1415 31.3 966 45.9 Dietary NOEL of 50 138450 1415 97.8 966 143.3 AUC0-infinity in rats (based on data from 6.45 mg/kg bw kinetic study) AUC0-infinity in humans (2% on head) MOE AUC0-infinity in humans (1% on head) MOE Gavage dose of 4 (NOAEL used by the SCCP) 16519 1415 11.6 966 17.1 Gavage NOAEL of 8 33038 1415 23.3 966 34.2 Gavage NOAEL of 16 66076 1415 46.7 966 68.4 Dietary NOEL of 50 206488 1415 145.9 966 213.8; CITATION_NUMBERS=[]; DETAILS_JSON={"cas_number":"106-50-3","citation":"","dose":"MOE Gavage dose of 4 (NOAEL used by the SCCP) 11076 1415 7.8 966 11.5 Gavage NOAEL of 8 22152 1415 15.6 966 22.2 Gavage NOAEL of 16 44304 1415 31.3 966 45.9 Dietary NOEL of 50 138450 1415 97.8 966 143.3 AUC0-infinity in rats (based on data from 6.45 mg/kg bw kinetic study) AUC0-infinity in humans (2% on head) MOE AUC0-infinity in humans (1% on h...","duration":"","effect":"MOE Gavage dose of 4 (NOAEL used by the SCCP) 11076 1415 7.8 966 11.5 Gavage NOAEL of 8 22152 1415 15.6 966 22.2 Gavage NOAEL of 16 44304 1415 31.3 966 45.9 Dietary NOEL of 50 138450 1415 97.8 966 143.3 AUC0-infinity in rats (based on data from 6.45 mg/kg bw kinetic study) AUC0-infinity in humans (2% on head) MOE AUC0-infinity in humans (1% on head) MOE Gavage dose of 4 (NOAEL used by the SCCP) 16519 1415 11.6 966 17.1 Gavage NOAEL of 8 33038 1415 23.3 966 34.2 Gavage NOAEL of 16 66076 1415 46.7 966 68.4 Dietary NOEL of 50 206488 1415 145.9 966 213.8","endpoint":"","ingredient":"s from temporary tattoos and clothing textiles. PPD is an extreme","loael_value":"","noael_unit":"%","noael_value":"1","page":61,"route":"oral","species":"rat","study_id":"sccs_o_094_noael_034"}

sccs_o_094.pdf

SOURCE_SUBDIR=sccs_o_094; REPORT_TITLE=OPINION ON p-Phenylenediamine COLIPA n° A7; OPINION_NUMBER=SCCS/1443/11; COMMITTEE=Scientific Committee on Consumer Safety (SCCS); REPORT_DATE=18 September 2012; VALUE_TEXT=4; DOSE=At the same dose levels, absolute and body weight-related kidney weights were increased for females.; EFFECT=16 mg/kg bw/day. At the same dose levels, absolute and body weight-related kidney weights were increased for females. However, no associated histopathological changes were noted. No treatment macroscopic or microscopic findings were recorded. Histopathological examination restricted significant finding to minimal myodegeneration on skeletal muscle on 1 male and 1 female of the high dose group (16 mg/kg bw). Based on these results, the NOEL of PPD was established at 4 mg/kg bw/day by the applicant and considered as NOAEL by the SCCNFP and SCCP. Ref.: 121 External expert review (18, subm V) In the expert review, it was stated that the liver and kidney weight increases at 8 and 16 mg/kg bw/d are the only changes in this study which were considered to be related to treatment with PPD. Such organ weight changes without associated clinical chemistry; CITATION=Ref.: 121 External expert review (18, subm V) In the expert review, it was stated that the liver and kidney weight increases at 8 and 16 mg/kg bw/d are the only changes in this study whi; CITATION_NUMBERS=[121,18,8,16]; REFERENCE=Ref.: 121 External expert review (18, subm V) In the expert review, it was stated that the liver and kidney weight increases at 8 and 16 mg/kg bw/d are the only changes in this study whi; DETAILS_JSON={"cas_number":"106-50-3","citation":"Ref.: 121 External expert review (18, subm V) In the expert review, it was stated that the liver and kidney weight increases at 8 and 16 mg/kg bw/d are the only changes in this study whi","dose":"At the same dose levels, absolute and body weight-related kidney weights were increased for females.","duration":"","effect":"16 mg/kg bw/day. At the same dose levels, absolute and body weight-related kidney weights were increased for females. However, no associated histopathological changes were noted. No treatment macroscopic or microscopic findings were recorded. Histopathological examination restricted significant finding to minimal myodegeneration on skeletal muscle on 1 male and 1 female of the high dose group (16 mg/kg bw). Based on these results, the NOEL of PPD was established at 4 mg/kg bw/day by the applicant and considered as NOAEL by the SCCNFP and SCCP. Ref.: 121 External expert review (18, subm V) In the expert review, it was stated that the liver and kidney weight increases at 8 and 16 mg/kg bw/d are the only changes in this study which were considered to be related to treatment with PPD. Such organ weight changes without associated clinical chemistry","endpoint":"","ingredient":"s from temporary tattoos and clothing textiles. PPD is an extreme","loael_value":"","noael_unit":"mg/kg bw/day","noael_value":"4","page":16,"route":"","species":"","study_id":"sccs_o_094_noael_004"}

sccs_o_094.pdf

SOURCE_SUBDIR=sccs_o_094; REPORT_TITLE=OPINION ON p-Phenylenediamine COLIPA n° A7; OPINION_NUMBER=SCCS/1443/11; COMMITTEE=Scientific Committee on Consumer Safety (SCCS); REPORT_DATE=18 September 2012; VALUE_TEXT=4; DOSE=The external expert therefore concluded the following for this study: • The no observed effect level (NOEL) is 4 mg/kg bw/d • The no observed adverse effect level (NOAEL) is 16 mg/kg bw/d This conclusion confirmed the NOEL as cited in the original report.; EFFECT=SCCS/1443/11 Opinion on p-phenylenediamine ___________________________________________________________________________________________ 17 alterations and without any corresponding histopathological changes were considered to be adaptive in nature and non-adverse. The external expert therefore concluded the following for this study: • The no observed effect level (NOEL) is 4 mg/kg bw/d • The no observed adverse effect level (NOAEL) is 16 mg/kg bw/d This conclusion confirmed the NOEL as cited in the original report. It also expanded this original conclusion to include a judgement on adverse findings and defined the NOAEL for the study. Comment of the SCCS The SCCS agrees to this judgement of kidney and liver effects observed. However, also the observed myodegenerative effects need to be considered. It is well known that PPD and some substituted derivatives can induce myotoxicit; CITATION_NUMBERS=[]; DETAILS_JSON={"cas_number":"106-50-3","citation":"","dose":"The external expert therefore concluded the following for this study: • The no observed effect level (NOEL) is 4 mg/kg bw/d • The no observed adverse effect level (NOAEL) is 16 mg/kg bw/d This conclusion confirmed the NOEL as cited in the original report.","duration":"","effect":"SCCS/1443/11 Opinion on p-phenylenediamine ___________________________________________________________________________________________ 17 alterations and without any corresponding histopathological changes were considered to be adaptive in nature and non-adverse. The external expert therefore concluded the following for this study: • The no observed effect level (NOEL) is 4 mg/kg bw/d • The no observed adverse effect level (NOAEL) is 16 mg/kg bw/d This conclusion confirmed the NOEL as cited in the original report. It also expanded this original conclusion to include a judgement on adverse findings and defined the NOAEL for the study. Comment of the SCCS The SCCS agrees to this judgement of kidney and liver effects observed. However, also the observed myodegenerative effects need to be considered. It is well known that PPD and some substituted derivatives can induce myotoxicit","endpoint":"","ingredient":"s from temporary tattoos and clothing textiles. PPD is an extreme","loael_value":"","noael_unit":"mg/kg bw/d","noael_value":"4","page":17,"route":"","species":"","study_id":"sccs_o_094_noael_005"}

sccs_o_094.pdf

SOURCE_SUBDIR=sccs_o_094; REPORT_TITLE=OPINION ON p-Phenylenediamine COLIPA n° A7; OPINION_NUMBER=SCCS/1443/11; COMMITTEE=Scientific Committee on Consumer Safety (SCCS); REPORT_DATE=18 September 2012; VALUE_TEXT=4; DOSE=For the calculation of the MoS, a NOAEL of 4 mg/kg bw/d was used.; EFFECT=SCCS/1443/11 Opinion on p-phenylenediamine ___________________________________________________________________________________________ 59 3.3.13. Safety evaluation (including calculation of the MoS) • Evaluation based on Margin of Safety (MoS) In 2006 the SCCP concluded that, based on the classical MoS approach, the safety of p- phenylenediamine used as an oxidative hair dye at an applied concentration of 2% could not be warranted. For the calculation of the MoS, a NOAEL of 4 mg/kg bw/d was used. This NOAEL was derived from a 90 days oral toxicity study in which mean absolute and body- weight related liver and kidney weights were significantly increased for males and females, at 8 mg/kg bw/d and 16 mg/kg bw/d respectively, and minimal myodegeneration on skeletal muscle were observed in one male and one female of the high dose group. The MoS resulted in 77. The applicant proposed to base the safety on the comparison of AUCs (area under curve) described below. In the recent submissi; CITATION_NUMBERS=[]; DETAILS_JSON={"cas_number":"106-50-3","citation":"","dose":"For the calculation of the MoS, a NOAEL of 4 mg/kg bw/d was used.","duration":"90 days","effect":"SCCS/1443/11 Opinion on p-phenylenediamine ___________________________________________________________________________________________ 59 3.3.13. Safety evaluation (including calculation of the MoS) • Evaluation based on Margin of Safety (MoS) In 2006 the SCCP concluded that, based on the classical MoS approach, the safety of p- phenylenediamine used as an oxidative hair dye at an applied concentration of 2% could not be warranted. For the calculation of the MoS, a NOAEL of 4 mg/kg bw/d was used. This NOAEL was derived from a 90 days oral toxicity study in which mean absolute and body- weight related liver and kidney weights were significantly increased for males and females, at 8 mg/kg bw/d and 16 mg/kg bw/d respectively, and minimal myodegeneration on skeletal muscle were observed in one male and one female of the high dose group. The MoS resulted in 77. The applicant proposed to base the safety on the comparison of AUCs (area under curve) described below. In the recent submissi","endpoint":"","ingredient":"s from temporary tattoos and clothing textiles. PPD is an extreme","loael_value":"","noael_unit":"mg/kg bw/d","noael_value":"4","page":59,"route":"oral","species":"","study_id":"sccs_o_094_noael_015"}

sccs_o_094.pdf

SOURCE_SUBDIR=sccs_o_094; REPORT_TITLE=OPINION ON p-Phenylenediamine COLIPA n° A7; OPINION_NUMBER=SCCS/1443/11; COMMITTEE=Scientific Committee on Consumer Safety (SCCS); REPORT_DATE=18 September 2012; VALUE_TEXT=4; DOSE=and kidney weights were significantly increased for males and females, at 8 mg/kg bw/d and 16 mg/kg bw/d respectively, and minimal myodegeneration on skeletal muscle were observed in one male and one female of the high dose group.; EFFECT=and kidney weights were significantly increased for males and females, at 8 mg/kg bw/d and 16 mg/kg bw/d respectively, and minimal myodegeneration on skeletal muscle were observed in one male and one female of the high dose group. The MoS resulted in 77. The applicant proposed to base the safety on the comparison of AUCs (area under curve) described below. In the recent submission of 2011, the applicant, based on the expert review of the 90 days toxicity study, proposed that 4 mg/kg bw/d should be considered as a NOEL and not as a NOAEL, as the increase in body-weight related liver and kidney weights observed were considered mild modifications, not associated with histopathological or clinical pathology changes and adaptive, thus non–adverse. Therefore, the NOAEL from this study should then be 16 mg/kg bw/d (the highest dose tested). The SCCS agrees to this judgement of kidney and liver effects observed and that in the 90 days toxicity study, 4 mg/kg bw/d could be considered as a NOEL instead of a NOAEL for these effects. The i; CITATION_NUMBERS=[]; DETAILS_JSON={"cas_number":"106-50-3","citation":"","dose":"and kidney weights were significantly increased for males and females, at 8 mg/kg bw/d and 16 mg/kg bw/d respectively, and minimal myodegeneration on skeletal muscle were observed in one male and one female of the high dose group.","duration":"90 days","effect":"and kidney weights were significantly increased for males and females, at 8 mg/kg bw/d and 16 mg/kg bw/d respectively, and minimal myodegeneration on skeletal muscle were observed in one male and one female of the high dose group. The MoS resulted in 77. The applicant proposed to base the safety on the comparison of AUCs (area under curve) described below. In the recent submission of 2011, the applicant, based on the expert review of the 90 days toxicity study, proposed that 4 mg/kg bw/d should be considered as a NOEL and not as a NOAEL, as the increase in body-weight related liver and kidney weights observed were considered mild modifications, not associated with histopathological or clinical pathology changes and adaptive, thus non–adverse. Therefore, the NOAEL from this study should then be 16 mg/kg bw/d (the highest dose tested). The SCCS agrees to this judgement of kidney and liver effects observed and that in the 90 days toxicity study, 4 mg/kg bw/d could be considered as a NOEL instead of a NOAEL for these effects. The i","endpoint":"","ingredient":"s from temporary tattoos and clothing textiles. PPD is an extreme","loael_value":"","noael_unit":"mg/kg bw/d","noael_value":"4","page":59,"route":"","species":"","study_id":"sccs_o_094_noael_016"}

sccs_o_094.pdf

SOURCE_SUBDIR=sccs_o_094; REPORT_TITLE=OPINION ON p-Phenylenediamine COLIPA n° A7; OPINION_NUMBER=SCCS/1443/11; COMMITTEE=Scientific Committee on Consumer Safety (SCCS); REPORT_DATE=18 September 2012; VALUE_TEXT=4; DOSE=s were significantly increased for males and females, at 8 mg/kg bw/d and 16 mg/kg bw/d respectively, and minimal myodegeneration on skeletal muscle were observed in one male and one female of the high dose group.; EFFECT=s were significantly increased for males and females, at 8 mg/kg bw/d and 16 mg/kg bw/d respectively, and minimal myodegeneration on skeletal muscle were observed in one male and one female of the high dose group. The MoS resulted in 77. The applicant proposed to base the safety on the comparison of AUCs (area under curve) described below. In the recent submission of 2011, the applicant, based on the expert review of the 90 days toxicity study, proposed that 4 mg/kg bw/d should be considered as a NOEL and not as a NOAEL, as the increase in body-weight related liver and kidney weights observed were considered mild modifications, not associated with histopathological or clinical pathology changes and adaptive, thus non–adverse. Therefore, the NOAEL from this study should then be 16 mg/kg bw/d (the highest dose tested). The SCCS agrees to this judgement of kidney and liver effects observed and that in the 90 days toxicity study, 4 mg/kg bw/d could be considered as a NOEL instead of a NOAEL for these effects. The increase in body-wei; CITATION_NUMBERS=[]; DETAILS_JSON={"cas_number":"106-50-3","citation":"","dose":"s were significantly increased for males and females, at 8 mg/kg bw/d and 16 mg/kg bw/d respectively, and minimal myodegeneration on skeletal muscle were observed in one male and one female of the high dose group.","duration":"90 days","effect":"s were significantly increased for males and females, at 8 mg/kg bw/d and 16 mg/kg bw/d respectively, and minimal myodegeneration on skeletal muscle were observed in one male and one female of the high dose group. The MoS resulted in 77. The applicant proposed to base the safety on the comparison of AUCs (area under curve) described below. In the recent submission of 2011, the applicant, based on the expert review of the 90 days toxicity study, proposed that 4 mg/kg bw/d should be considered as a NOEL and not as a NOAEL, as the increase in body-weight related liver and kidney weights observed were considered mild modifications, not associated with histopathological or clinical pathology changes and adaptive, thus non–adverse. Therefore, the NOAEL from this study should then be 16 mg/kg bw/d (the highest dose tested). The SCCS agrees to this judgement of kidney and liver effects observed and that in the 90 days toxicity study, 4 mg/kg bw/d could be considered as a NOEL instead of a NOAEL for these effects. The increase in body-wei","endpoint":"","ingredient":"s from temporary tattoos and clothing textiles. PPD is an extreme","loael_value":"","noael_unit":"mg/kg bw/d","noael_value":"4","page":59,"route":"","species":"","study_id":"sccs_o_094_noael_017"}

sccs_o_094.pdf

SOURCE_SUBDIR=sccs_o_094; REPORT_TITLE=OPINION ON p-Phenylenediamine COLIPA n° A7; OPINION_NUMBER=SCCS/1443/11; COMMITTEE=Scientific Committee on Consumer Safety (SCCS); REPORT_DATE=18 September 2012; VALUE_TEXT=4; DOSE=that 4 mg/kg bw/d should be considered as a NOEL and not as a NOAEL, as the increase in body-weight related liver and kidney weights observed were considered mild modifications, not associated with histopathological or clinical pathology changes and adaptive, thus non–adverse.; EFFECT=that 4 mg/kg bw/d should be considered as a NOEL and not as a NOAEL, as the increase in body-weight related liver and kidney weights observed were considered mild modifications, not associated with histopathological or clinical pathology changes and adaptive, thus non–adverse. Therefore, the NOAEL from this study should then be 16 mg/kg bw/d (the highest dose tested). The SCCS agrees to this judgement of kidney and liver effects observed and that in the 90 days toxicity study, 4 mg/kg bw/d could be considered as a NOEL instead of a NOAEL for these effects. The increase in body-weight related liver and kidney weights at the dose of 8 and 16 mg/kg bw/d, even if statistically significant remains still slight. Moreover they were not associated with histopathological changes or clinical chemistry alterations. However, the observed myodegenerative effects also need to be considered. It is well known that PPD and some substituted derivatives can induce myotoxicity (e.g. even after 3 days of administration of 36.2 mg/kg bw, see Ref. I).; CITATION_NUMBERS=[]; DETAILS_JSON={"cas_number":"106-50-3","citation":"","dose":"that 4 mg/kg bw/d should be considered as a NOEL and not as a NOAEL, as the increase in body-weight related liver and kidney weights observed were considered mild modifications, not associated with histopathological or clinical pathology changes and adaptive, thus non–adverse.","duration":"90 days","effect":"that 4 mg/kg bw/d should be considered as a NOEL and not as a NOAEL, as the increase in body-weight related liver and kidney weights observed were considered mild modifications, not associated with histopathological or clinical pathology changes and adaptive, thus non–adverse. Therefore, the NOAEL from this study should then be 16 mg/kg bw/d (the highest dose tested). The SCCS agrees to this judgement of kidney and liver effects observed and that in the 90 days toxicity study, 4 mg/kg bw/d could be considered as a NOEL instead of a NOAEL for these effects. The increase in body-weight related liver and kidney weights at the dose of 8 and 16 mg/kg bw/d, even if statistically significant remains still slight. Moreover they were not associated with histopathological changes or clinical chemistry alterations. However, the observed myodegenerative effects also need to be considered. It is well known that PPD and some substituted derivatives can induce myotoxicity (e.g. even after 3 days of administration of 36.2 mg/kg bw, see Ref. I).","endpoint":"","ingredient":"s from temporary tattoos and clothing textiles. PPD is an extreme","loael_value":"","noael_unit":"mg/kg bw/d","noael_value":"4","page":59,"route":"","species":"","study_id":"sccs_o_094_noael_019"}

sccs_o_094.pdf

SOURCE_SUBDIR=sccs_o_094; REPORT_TITLE=OPINION ON p-Phenylenediamine COLIPA n° A7; OPINION_NUMBER=SCCS/1443/11; COMMITTEE=Scientific Committee on Consumer Safety (SCCS); REPORT_DATE=18 September 2012; VALUE_TEXT=4; DOSE=Therefore, the NOAEL from this study should then be 16 mg/kg bw/d (the highest dose tested).; EFFECT=should be considered as a NOEL and not as a NOAEL, as the increase in body-weight related liver and kidney weights observed were considered mild modifications, not associated with histopathological or clinical pathology changes and adaptive, thus non–adverse. Therefore, the NOAEL from this study should then be 16 mg/kg bw/d (the highest dose tested). The SCCS agrees to this judgement of kidney and liver effects observed and that in the 90 days toxicity study, 4 mg/kg bw/d could be considered as a NOEL instead of a NOAEL for these effects. The increase in body-weight related liver and kidney weights at the dose of 8 and 16 mg/kg bw/d, even if statistically significant remains still slight. Moreover they were not associated with histopathological changes or clinical chemistry alterations. However, the observed myodegenerative effects also need to be considered. It is well known that PPD and some substituted derivatives can induce myotoxicity (e.g. even after 3 days of administration of 36.2 mg/kg bw, see Ref. I). This myodegenerati; CITATION_NUMBERS=[]; DETAILS_JSON={"cas_number":"106-50-3","citation":"","dose":"Therefore, the NOAEL from this study should then be 16 mg/kg bw/d (the highest dose tested).","duration":"90 days","effect":"should be considered as a NOEL and not as a NOAEL, as the increase in body-weight related liver and kidney weights observed were considered mild modifications, not associated with histopathological or clinical pathology changes and adaptive, thus non–adverse. Therefore, the NOAEL from this study should then be 16 mg/kg bw/d (the highest dose tested). The SCCS agrees to this judgement of kidney and liver effects observed and that in the 90 days toxicity study, 4 mg/kg bw/d could be considered as a NOEL instead of a NOAEL for these effects. The increase in body-weight related liver and kidney weights at the dose of 8 and 16 mg/kg bw/d, even if statistically significant remains still slight. Moreover they were not associated with histopathological changes or clinical chemistry alterations. However, the observed myodegenerative effects also need to be considered. It is well known that PPD and some substituted derivatives can induce myotoxicity (e.g. even after 3 days of administration of 36.2 mg/kg bw, see Ref. I). This myodegenerati","endpoint":"","ingredient":"s from temporary tattoos and clothing textiles. PPD is an extreme","loael_value":"","noael_unit":"mg/kg bw/d","noael_value":"4","page":59,"route":"","species":"","study_id":"sccs_o_094_noael_020"}

sccs_o_094.pdf

SOURCE_SUBDIR=sccs_o_094; REPORT_TITLE=OPINION ON p-Phenylenediamine COLIPA n° A7; OPINION_NUMBER=SCCS/1443/11; COMMITTEE=Scientific Committee on Consumer Safety (SCCS); REPORT_DATE=18 September 2012; VALUE_TEXT=4; DOSE=SCCS/1443/11 Opinion on p-phenylenediamine ___________________________________________________________________________________________ 60 In its 2006 opinion, the SCCP also calculated a toxicokinetic data based MoS by comparing plasma AUC in rat following oral administration of PPD at the NOAEL (4 mg/kg bw/d) to plasma AUC in human following der...; EFFECT=SCCS/1443/11 Opinion on p-phenylenediamine ___________________________________________________________________________________________ 60 In its 2006 opinion, the SCCP also calculated a toxicokinetic data based MoS by comparing plasma AUC in rat following oral administration of PPD at the NOAEL (4 mg/kg bw/d) to plasma AUC in human following dermal application to hair dye containing PPD. A single oral administration of [14C]-PPD to male and female rats of a dose corresponding to the NOAEL of the 90-day oral toxicity study (4.0 mg/kg bw) produced a measured systemic exposure characterised by plasma Cmax values for both sexes of approximately 3.9 µg-eq/ml (4.10 ± 0.04 and 3.73 ± 0.23 µg/ml in males and females, respectively) and a mean plasma AUC0-24h of approximately 10.8 µg-eq * hr/ml. In human volunt; CITATION_NUMBERS=[]; DETAILS_JSON={"cas_number":"106-50-3","citation":"","dose":"SCCS/1443/11 Opinion on p-phenylenediamine ___________________________________________________________________________________________ 60 In its 2006 opinion, the SCCP also calculated a toxicokinetic data based MoS by comparing plasma AUC in rat following oral administration of PPD at the NOAEL (4 mg/kg bw/d) to plasma AUC in human following der...","duration":"90-day","effect":"SCCS/1443/11 Opinion on p-phenylenediamine ___________________________________________________________________________________________ 60 In its 2006 opinion, the SCCP also calculated a toxicokinetic data based MoS by comparing plasma AUC in rat following oral administration of PPD at the NOAEL (4 mg/kg bw/d) to plasma AUC in human following dermal application to hair dye containing PPD. A single oral administration of [14C]-PPD to male and female rats of a dose corresponding to the NOAEL of the 90-day oral toxicity study (4.0 mg/kg bw) produced a measured systemic exposure characterised by plasma Cmax values for both sexes of approximately 3.9 µg-eq/ml (4.10 ± 0.04 and 3.73 ± 0.23 µg/ml in males and females, respectively) and a mean plasma AUC0-24h of approximately 10.8 µg-eq * hr/ml. In human volunt","endpoint":"","ingredient":"s from temporary tattoos and clothing textiles. PPD is an extreme","loael_value":"","noael_unit":"mg/kg bw/d","noael_value":"4","page":60,"route":"oral","species":"rat","study_id":"sccs_o_094_noael_024"}

sccs_o_094.pdf

SOURCE_SUBDIR=sccs_o_094; REPORT_TITLE=OPINION ON p-Phenylenediamine COLIPA n° A7; OPINION_NUMBER=SCCS/1443/11; COMMITTEE=Scientific Committee on Consumer Safety (SCCS); REPORT_DATE=18 September 2012; VALUE_TEXT=4.0; DOSE=SCCS/1443/11 Opinion on p-phenylenediamine ___________________________________________________________________________________________ 60 In its 2006 opinion, the SCCP also calculated a toxicokinetic data based MoS by comparing plasma AUC in rat following oral administration of PPD at the NOAEL (4 mg/kg bw/d) to plasma AUC in human following der...; EFFECT=SCCS/1443/11 Opinion on p-phenylenediamine ___________________________________________________________________________________________ 60 In its 2006 opinion, the SCCP also calculated a toxicokinetic data based MoS by comparing plasma AUC in rat following oral administration of PPD at the NOAEL (4 mg/kg bw/d) to plasma AUC in human following dermal application to hair dye containing PPD. A single oral administration of [14C]-PPD to male and female rats of a dose corresponding to the NOAEL of the 90-day oral toxicity study (4.0 mg/kg bw) produced a measured systemic exposure characterised by plasma Cmax values for both sexes of approximately 3.9 µg-eq/ml (4.10 ± 0.04 and 3.73 ± 0.23 µg/ml in males and females, respectively) and a mean plasma AUC0-24h of approximately 10.8 µg-eq * hr/ml. In human volunteers (N=8), hair dyeing with a dark-shade, 2.0% [14C]-PPD-containing hair dye produced measurable plasma values with a Cmax of 0.087 µg-eq/ml and a mean AUC0-24h of 0.66 µgeq*hr/ml (mean value of ind; CITATION_NUMBERS=[]; DETAILS_JSON={"cas_number":"106-50-3","citation":"","dose":"SCCS/1443/11 Opinion on p-phenylenediamine ___________________________________________________________________________________________ 60 In its 2006 opinion, the SCCP also calculated a toxicokinetic data based MoS by comparing plasma AUC in rat following oral administration of PPD at the NOAEL (4 mg/kg bw/d) to plasma AUC in human following der...","duration":"90-day","effect":"SCCS/1443/11 Opinion on p-phenylenediamine ___________________________________________________________________________________________ 60 In its 2006 opinion, the SCCP also calculated a toxicokinetic data based MoS by comparing plasma AUC in rat following oral administration of PPD at the NOAEL (4 mg/kg bw/d) to plasma AUC in human following dermal application to hair dye containing PPD. A single oral administration of [14C]-PPD to male and female rats of a dose corresponding to the NOAEL of the 90-day oral toxicity study (4.0 mg/kg bw) produced a measured systemic exposure characterised by plasma Cmax values for both sexes of approximately 3.9 µg-eq/ml (4.10 ± 0.04 and 3.73 ± 0.23 µg/ml in males and females, respectively) and a mean plasma AUC0-24h of approximately 10.8 µg-eq * hr/ml. In human volunteers (N=8), hair dyeing with a dark-shade, 2.0% [14C]-PPD-containing hair dye produced measurable plasma values with a Cmax of 0.087 µg-eq/ml and a mean AUC0-24h of 0.66 µgeq*hr/ml (mean value of ind","endpoint":"","ingredient":"s from temporary tattoos and clothing textiles. PPD is an extreme","loael_value":"","noael_unit":"mg/kg bw","noael_value":"4.0","page":60,"route":"oral","species":"rat","study_id":"sccs_o_094_noael_025"}

sccs_o_094.pdf

SOURCE_SUBDIR=sccs_o_094; REPORT_TITLE=OPINION ON p-Phenylenediamine COLIPA n° A7; OPINION_NUMBER=SCCS/1443/11; COMMITTEE=Scientific Committee on Consumer Safety (SCCS); REPORT_DATE=18 September 2012; VALUE_TEXT=4; DOSE=At 25 mg/kg bw only orange traces in the bedding were seen probably due to coloured urine.; EFFECT=mation, swelling of conjunctivae, gait, tremor, subdued behaviour and/or piloerection). At 25 mg/kg bw only orange traces in the bedding were seen probably due to coloured urine. Several studies on systemic toxicity have shown that the most sensitive target organ is the skeletal muscle, with a rhabdomyolysis being experimentally observed following oral application in the rat at levels down to 16 mg/kg bw. Myocardial damage is also described with PPD-related hair dye poisonings in humans. • From a 90 day study, a NOAEL of 4 mg/kg bw/d was obtained and was used as the basis for the safety evaluation by the SCCP in 2006. In an expert review submitted in the recent dossier it was argued that liver and kidney weight increases at 8 and 16 mg/kg bw/d are the only changes in this study which are considered to be related to treatment with PPD. Such organ weight changes without associated clinical chemistry alterations and without any corresponding histopathological changes were considered to be adaptive in nature and non-adverse. The ap; CITATION_NUMBERS=[]; DETAILS_JSON={"cas_number":"106-50-3","citation":"","dose":"At 25 mg/kg bw only orange traces in the bedding were seen probably due to coloured urine.","duration":"90 day","effect":"mation, swelling of conjunctivae, gait, tremor, subdued behaviour and/or piloerection). At 25 mg/kg bw only orange traces in the bedding were seen probably due to coloured urine. Several studies on systemic toxicity have shown that the most sensitive target organ is the skeletal muscle, with a rhabdomyolysis being experimentally observed following oral application in the rat at levels down to 16 mg/kg bw. Myocardial damage is also described with PPD-related hair dye poisonings in humans. • From a 90 day study, a NOAEL of 4 mg/kg bw/d was obtained and was used as the basis for the safety evaluation by the SCCP in 2006. In an expert review submitted in the recent dossier it was argued that liver and kidney weight increases at 8 and 16 mg/kg bw/d are the only changes in this study which are considered to be related to treatment with PPD. Such organ weight changes without associated clinical chemistry alterations and without any corresponding histopathological changes were considered to be adaptive in nature and non-adverse. The ap","endpoint":"","ingredient":"s from temporary tattoos and clothing textiles. PPD is an extreme","loael_value":"","noael_unit":"mg/kg bw/d","noael_value":"4","page":62,"route":"oral","species":"rat","study_id":"sccs_o_094_noael_036"}

sccs_o_094.pdf

SOURCE_SUBDIR=sccs_o_094; REPORT_TITLE=OPINION ON p-Phenylenediamine COLIPA n° A7; OPINION_NUMBER=SCCS/1443/11; COMMITTEE=Scientific Committee on Consumer Safety (SCCS); REPORT_DATE=18 September 2012; VALUE_TEXT=4; DOSE=In an expert review submitted in the recent dossier it was argued that liver and kidney weight increases at 8 and 16 mg/kg bw/d are the only changes in this study which are considered to be related to treatment with PPD.; EFFECT=ty evaluation by the SCCP in 2006. In an expert review submitted in the recent dossier it was argued that liver and kidney weight increases at 8 and 16 mg/kg bw/d are the only changes in this study which are considered to be related to treatment with PPD. Such organ weight changes without associated clinical chemistry alterations and without any corresponding histopathological changes were considered to be adaptive in nature and non-adverse. The applicant concluded for this study that the no observed effect level (NOEL) is 4 mg/kg bw/d and the no observed adverse effect level (NOAEL) is 16 mg/kg bw/d. The SCCS agrees to this judgement of kidney and liver effects observed. However, myodegenerative effects also need to be considered. It is well known that PPD and some substituted derivatives can induce myotoxicity (e.g. even after 3 days of administration of 36.2 mg/kg bw, see Ref. I). This myodegeneration in the skeletal muscle was also noted in the 28-day study in 3 females given 40 mg/kg bw/d (Ref. 120). Minimal myodegeneratio; CITATION=(Ref. 120); CITATION_NUMBERS=[120]; REFERENCE=(Ref. 120); DETAILS_JSON={"cas_number":"106-50-3","citation":"(Ref. 120)","dose":"In an expert review submitted in the recent dossier it was argued that liver and kidney weight increases at 8 and 16 mg/kg bw/d are the only changes in this study which are considered to be related to treatment with PPD.","duration":"3 days","effect":"ty evaluation by the SCCP in 2006. In an expert review submitted in the recent dossier it was argued that liver and kidney weight increases at 8 and 16 mg/kg bw/d are the only changes in this study which are considered to be related to treatment with PPD. Such organ weight changes without associated clinical chemistry alterations and without any corresponding histopathological changes were considered to be adaptive in nature and non-adverse. The applicant concluded for this study that the no observed effect level (NOEL) is 4 mg/kg bw/d and the no observed adverse effect level (NOAEL) is 16 mg/kg bw/d. The SCCS agrees to this judgement of kidney and liver effects observed. However, myodegenerative effects also need to be considered. It is well known that PPD and some substituted derivatives can induce myotoxicity (e.g. even after 3 days of administration of 36.2 mg/kg bw, see Ref. I). This myodegeneration in the skeletal muscle was also noted in the 28-day study in 3 females given 40 mg/kg bw/d (Ref. 120). Minimal myodegeneratio","endpoint":"","ingredient":"s from temporary tattoos and clothing textiles. PPD is an extreme","loael_value":"","noael_unit":"mg/kg bw/d","noael_value":"4","page":62,"route":"","species":"","study_id":"sccs_o_094_noael_037"}

sccs_o_094.pdf

SOURCE_SUBDIR=sccs_o_094; REPORT_TITLE=OPINION ON p-Phenylenediamine COLIPA n° A7; OPINION_NUMBER=SCCS/1443/11; COMMITTEE=Scientific Committee on Consumer Safety (SCCS); REPORT_DATE=18 September 2012; VALUE_TEXT=4; DOSE=In an expert review submitted in the recent dossier it was argued that liver and kidney weight increases at 8 and 16 mg/kg bw/d are the only changes in this study which are considered to be related to treatment with PPD.; EFFECT=006. In an expert review submitted in the recent dossier it was argued that liver and kidney weight increases at 8 and 16 mg/kg bw/d are the only changes in this study which are considered to be related to treatment with PPD. Such organ weight changes without associated clinical chemistry alterations and without any corresponding histopathological changes were considered to be adaptive in nature and non-adverse. The applicant concluded for this study that the no observed effect level (NOEL) is 4 mg/kg bw/d and the no observed adverse effect level (NOAEL) is 16 mg/kg bw/d. The SCCS agrees to this judgement of kidney and liver effects observed. However, myodegenerative effects also need to be considered. It is well known that PPD and some substituted derivatives can induce myotoxicity (e.g. even after 3 days of administration of 36.2 mg/kg bw, see Ref. I). This myodegeneration in the skeletal muscle was also noted in the 28-day study in 3 females given 40 mg/kg bw/d (Ref. 120). Minimal myodegeneration; CITATION=(Ref. 120); CITATION_NUMBERS=[120]; REFERENCE=(Ref. 120); DETAILS_JSON={"cas_number":"106-50-3","citation":"(Ref. 120)","dose":"In an expert review submitted in the recent dossier it was argued that liver and kidney weight increases at 8 and 16 mg/kg bw/d are the only changes in this study which are considered to be related to treatment with PPD.","duration":"3 days","effect":"006. In an expert review submitted in the recent dossier it was argued that liver and kidney weight increases at 8 and 16 mg/kg bw/d are the only changes in this study which are considered to be related to treatment with PPD. Such organ weight changes without associated clinical chemistry alterations and without any corresponding histopathological changes were considered to be adaptive in nature and non-adverse. The applicant concluded for this study that the no observed effect level (NOEL) is 4 mg/kg bw/d and the no observed adverse effect level (NOAEL) is 16 mg/kg bw/d. The SCCS agrees to this judgement of kidney and liver effects observed. However, myodegenerative effects also need to be considered. It is well known that PPD and some substituted derivatives can induce myotoxicity (e.g. even after 3 days of administration of 36.2 mg/kg bw, see Ref. I). This myodegeneration in the skeletal muscle was also noted in the 28-day study in 3 females given 40 mg/kg bw/d (Ref. 120). Minimal myodegeneration","endpoint":"","ingredient":"s from temporary tattoos and clothing textiles. PPD is an extreme","loael_value":"","noael_unit":"mg/kg bw/d","noael_value":"4","page":62,"route":"","species":"","study_id":"sccs_o_094_noael_038"}

sccs_o_094.pdf

SOURCE_SUBDIR=sccs_o_094; REPORT_TITLE=OPINION ON p-Phenylenediamine COLIPA n° A7; OPINION_NUMBER=SCCS/1443/11; COMMITTEE=Scientific Committee on Consumer Safety (SCCS); REPORT_DATE=18 September 2012; VALUE_TEXT=Gavage dose of 4 (NOAEL used by the SCCP); DOSE=Gavage dose of 4 (NOAEL used by the SCCP) | 11076 | 1415 | 7.8 | 966 | 11.5; EFFECT=Unlabeled table on page 61: Gavage dose of 4 (NOAEL used by the SCCP) | 11076 | 1415 | 7.8 | 966 | 11.5; CITATION_NUMBERS=[]; DETAILS_JSON={"cas_number":"106-50-3","citation":"","dose":"Gavage dose of 4 (NOAEL used by the SCCP) | 11076 | 1415 | 7.8 | 966 | 11.5","duration":"","effect":"Unlabeled table on page 61: Gavage dose of 4 (NOAEL used by the SCCP) | 11076 | 1415 | 7.8 | 966 | 11.5","endpoint":"","ingredient":"s from temporary tattoos and clothing textiles. PPD is an extreme","loael_value":"","noael_unit":"","noael_value":"Gavage dose of 4 (NOAEL used by the SCCP)","page":61,"route":"oral","species":"","study_id":"sccs_o_094_noael_056"}

sccs_o_094.pdf

SOURCE_SUBDIR=sccs_o_094; REPORT_TITLE=OPINION ON p-Phenylenediamine COLIPA n° A7; OPINION_NUMBER=SCCS/1443/11; COMMITTEE=Scientific Committee on Consumer Safety (SCCS); REPORT_DATE=18 September 2012; VALUE_TEXT=Gavage dose of 4 (NOAEL used by the SCCP); DOSE=Gavage dose of 4 (NOAEL used by the SCCP) | 16519 | 1415 | 11.6 | 966 | 17.1; EFFECT=Unlabeled table on page 61: Gavage dose of 4 (NOAEL used by the SCCP) | 16519 | 1415 | 11.6 | 966 | 17.1; CITATION_NUMBERS=[]; DETAILS_JSON={"cas_number":"106-50-3","citation":"","dose":"Gavage dose of 4 (NOAEL used by the SCCP) | 16519 | 1415 | 11.6 | 966 | 17.1","duration":"","effect":"Unlabeled table on page 61: Gavage dose of 4 (NOAEL used by the SCCP) | 16519 | 1415 | 11.6 | 966 | 17.1","endpoint":"","ingredient":"s from temporary tattoos and clothing textiles. PPD is an extreme","loael_value":"","noael_unit":"","noael_value":"Gavage dose of 4 (NOAEL used by the SCCP)","page":61,"route":"oral","species":"","study_id":"sccs_o_094_noael_060"}

sccs_o_094.pdf

SOURCE_SUBDIR=sccs_o_094; REPORT_TITLE=OPINION ON p-Phenylenediamine COLIPA n° A7; OPINION_NUMBER=SCCS/1443/11; COMMITTEE=Scientific Committee on Consumer Safety (SCCS); REPORT_DATE=18 September 2012; VALUE_TEXT=6.45; DOSE=Margins of exposure (MOE) derived based on the systemic exposure of rats treated with PPD in toxicity studies and humans exposed to hair dyes providing either 2% or 1% PPD on head.; EFFECT=subm. V) in which 1% PPD was applied on head. Margins of exposure (MOE) derived based on the systemic exposure of rats treated with PPD in toxicity studies and humans exposed to hair dyes providing either 2% or 1% PPD on head. Dose in rats (mg/kg bw) AUC0-infinity in rats (based on data from 4 mg/kg bw kinetic study) AUC0-infinity in humans (2% on head) MOE AUC0-infinity in humans (1% on head) MOE Gavage dose of 4 (NOAEL used by the SCCP) 11076 1415 7.8 966 11.5 Gavage NOAEL of 8 22152 1415 15.6 966 22.2 Gavage NOAEL of 16 44304 1415 31.3 966 45.9 Dietary NOEL of 50 138450 1415 97.8 966 143.3 AUC0-infinity in rats (based on data from 6.45 mg/kg bw kinetic study) AUC0-infinity in humans (2% on head) MOE AUC0-infinity in humans (1% on head) MOE Gavage dose of 4 (NOAEL used by the SCCP) 16519 1415 11.6 966 17.1 Gavage NOAEL of 8 33038 1415 23.3 966 34.2 Gavage NOAEL of 16 66076 1415 46.7 966 68.4 Dietary NOEL of 50 206488 1415 145.9 966 213.8; CITATION_NUMBERS=[]; DETAILS_JSON={"cas_number":"106-50-3","citation":"","dose":"Margins of exposure (MOE) derived based on the systemic exposure of rats treated with PPD in toxicity studies and humans exposed to hair dyes providing either 2% or 1% PPD on head.","duration":"","effect":"subm. V) in which 1% PPD was applied on head. Margins of exposure (MOE) derived based on the systemic exposure of rats treated with PPD in toxicity studies and humans exposed to hair dyes providing either 2% or 1% PPD on head. Dose in rats (mg/kg bw) AUC0-infinity in rats (based on data from 4 mg/kg bw kinetic study) AUC0-infinity in humans (2% on head) MOE AUC0-infinity in humans (1% on head) MOE Gavage dose of 4 (NOAEL used by the SCCP) 11076 1415 7.8 966 11.5 Gavage NOAEL of 8 22152 1415 15.6 966 22.2 Gavage NOAEL of 16 44304 1415 31.3 966 45.9 Dietary NOEL of 50 138450 1415 97.8 966 143.3 AUC0-infinity in rats (based on data from 6.45 mg/kg bw kinetic study) AUC0-infinity in humans (2% on head) MOE AUC0-infinity in humans (1% on head) MOE Gavage dose of 4 (NOAEL used by the SCCP) 16519 1415 11.6 966 17.1 Gavage NOAEL of 8 33038 1415 23.3 966 34.2 Gavage NOAEL of 16 66076 1415 46.7 966 68.4 Dietary NOEL of 50 206488 1415 145.9 966 213.8","endpoint":"","ingredient":"s from temporary tattoos and clothing textiles. PPD is an extreme","loael_value":"","noael_unit":"mg/kg bw","noael_value":"6.45","page":61,"route":"oral","species":"rat","study_id":"sccs_o_094_noael_029"}

sccs_o_094.pdf

SOURCE_SUBDIR=sccs_o_094; REPORT_TITLE=OPINION ON p-Phenylenediamine COLIPA n° A7; OPINION_NUMBER=SCCS/1443/11; COMMITTEE=Scientific Committee on Consumer Safety (SCCS); REPORT_DATE=18 September 2012; VALUE_TEXT=6.45; DOSE=Margins of exposure (MOE) derived based on the systemic exposure of rats treated with PPD in toxicity studies and humans exposed to hair dyes providing either 2% or 1% PPD on head.; EFFECT=. Margins of exposure (MOE) derived based on the systemic exposure of rats treated with PPD in toxicity studies and humans exposed to hair dyes providing either 2% or 1% PPD on head. Dose in rats (mg/kg bw) AUC0-infinity in rats (based on data from 4 mg/kg bw kinetic study) AUC0-infinity in humans (2% on head) MOE AUC0-infinity in humans (1% on head) MOE Gavage dose of 4 (NOAEL used by the SCCP) 11076 1415 7.8 966 11.5 Gavage NOAEL of 8 22152 1415 15.6 966 22.2 Gavage NOAEL of 16 44304 1415 31.3 966 45.9 Dietary NOEL of 50 138450 1415 97.8 966 143.3 AUC0-infinity in rats (based on data from 6.45 mg/kg bw kinetic study) AUC0-infinity in humans (2% on head) MOE AUC0-infinity in humans (1% on head) MOE Gavage dose of 4 (NOAEL used by the SCCP) 16519 1415 11.6 966 17.1 Gavage NOAEL of 8 33038 1415 23.3 966 34.2 Gavage NOAEL of 16 66076 1415 46.7 966 68.4 Dietary NOEL of 50 206488 1415 145.9 966 213.8; CITATION_NUMBERS=[]; DETAILS_JSON={"cas_number":"106-50-3","citation":"","dose":"Margins of exposure (MOE) derived based on the systemic exposure of rats treated with PPD in toxicity studies and humans exposed to hair dyes providing either 2% or 1% PPD on head.","duration":"","effect":". Margins of exposure (MOE) derived based on the systemic exposure of rats treated with PPD in toxicity studies and humans exposed to hair dyes providing either 2% or 1% PPD on head. Dose in rats (mg/kg bw) AUC0-infinity in rats (based on data from 4 mg/kg bw kinetic study) AUC0-infinity in humans (2% on head) MOE AUC0-infinity in humans (1% on head) MOE Gavage dose of 4 (NOAEL used by the SCCP) 11076 1415 7.8 966 11.5 Gavage NOAEL of 8 22152 1415 15.6 966 22.2 Gavage NOAEL of 16 44304 1415 31.3 966 45.9 Dietary NOEL of 50 138450 1415 97.8 966 143.3 AUC0-infinity in rats (based on data from 6.45 mg/kg bw kinetic study) AUC0-infinity in humans (2% on head) MOE AUC0-infinity in humans (1% on head) MOE Gavage dose of 4 (NOAEL used by the SCCP) 16519 1415 11.6 966 17.1 Gavage NOAEL of 8 33038 1415 23.3 966 34.2 Gavage NOAEL of 16 66076 1415 46.7 966 68.4 Dietary NOEL of 50 206488 1415 145.9 966 213.8","endpoint":"","ingredient":"s from temporary tattoos and clothing textiles. PPD is an extreme","loael_value":"","noael_unit":"mg/kg bw","noael_value":"6.45","page":61,"route":"oral","species":"rat","study_id":"sccs_o_094_noael_030"}

sccs_o_094.pdf

SOURCE_SUBDIR=sccs_o_094; REPORT_TITLE=OPINION ON p-Phenylenediamine COLIPA n° A7; OPINION_NUMBER=SCCS/1443/11; COMMITTEE=Scientific Committee on Consumer Safety (SCCS); REPORT_DATE=18 September 2012; VALUE_TEXT=8; DOSE=(e.g. even after 3 days of administration of 36.2 mg/kg bw, see Additional References H and I:; EFFECT=(e.g. even after 3 days of administration of 36.2 mg/kg bw, see Additional References H and I: Munday et al. 1990; Munday, Manns 1999). This myodegeneration in the skeletal muscle was also noted in the 28-day study in 3 females given 40 mg/kg bw/d (Ref. 120). Minimal myodegeneration on skeletal muscle was noted in the 90-day study on 1 male and 1 female of the high dose group (16 mg/kg bw). Although this was also observed in the respective control group a relation to PPD treatment cannot be excluded. SCCS sets the NOAEL at 8 mg/kg bw. A 12-week oral toxicity study was conducted in F344 rats (10 – 11 rats per group) with PPD administered in the diet at concentrations of 0.05, 0.1, 0.2 and 0.4% (or approximately 25, 50, 100 and 200 mg/kg bw/day respectively). Mortalities were observed at the theoretical dose of 200 mg/kg bw in 9 male rats and in 1 female rat. At the same dose level, a 50% reduction in body weight in both sexes as compared to controls, as well as increased relative liver and kidney weights were noted. A trend towar; CITATION=(Ref. 120); CITATION_NUMBERS=[120]; REFERENCE=(Ref. 120); DETAILS_JSON={"cas_number":"106-50-3","citation":"(Ref. 120)","dose":"(e.g. even after 3 days of administration of 36.2 mg/kg bw, see Additional References H and I:","duration":"3 days","effect":"(e.g. even after 3 days of administration of 36.2 mg/kg bw, see Additional References H and I: Munday et al. 1990; Munday, Manns 1999). This myodegeneration in the skeletal muscle was also noted in the 28-day study in 3 females given 40 mg/kg bw/d (Ref. 120). Minimal myodegeneration on skeletal muscle was noted in the 90-day study on 1 male and 1 female of the high dose group (16 mg/kg bw). Although this was also observed in the respective control group a relation to PPD treatment cannot be excluded. SCCS sets the NOAEL at 8 mg/kg bw. A 12-week oral toxicity study was conducted in F344 rats (10 – 11 rats per group) with PPD administered in the diet at concentrations of 0.05, 0.1, 0.2 and 0.4% (or approximately 25, 50, 100 and 200 mg/kg bw/day respectively). Mortalities were observed at the theoretical dose of 200 mg/kg bw in 9 male rats and in 1 female rat. At the same dose level, a 50% reduction in body weight in both sexes as compared to controls, as well as increased relative liver and kidney weights were noted. A trend towar","endpoint":"","ingredient":"s from temporary tattoos and clothing textiles. PPD is an extreme","loael_value":"","noael_unit":"mg/kg bw","noael_value":"8","page":17,"route":"oral","species":"rat","study_id":"sccs_o_094_noael_008"}

sccs_o_094.pdf

SOURCE_SUBDIR=sccs_o_094; REPORT_TITLE=OPINION ON p-Phenylenediamine COLIPA n° A7; OPINION_NUMBER=SCCS/1443/11; COMMITTEE=Scientific Committee on Consumer Safety (SCCS); REPORT_DATE=18 September 2012; VALUE_TEXT=8; DOSE=Food intake and body weight gain of treated group were similar to the controls.; EFFECT=r clinical signs considered related to the test article. Food intake and body weight gain of treated group were similar to the controls. At 16 mg/kg bw/d increased incidence of wet chin in both sexes and in wet inguen and/or wet perineum in females was observed. Neuropathology evaluations did not reveal abnormalities within the nervous system or skeletal muscle. There was no effect of the test substance on ocular tissue. The effects observed at 16 mg/kg bw/d are judged as pharmacological responses. Therefore, the NOEL was 8 mg/kg bw/d for both sexes; the NOAEL was 16 mg/kg bw/d. Ref.: Z Dermal toxicity A 90 day study has been carried out in the rabbit with the compound administered dermally twice weekly. Four hair-dye formulation containing 1, 2, 3 or 4% of para-phenylenediamine; CITATION=Ref.: Z Dermal toxicity A 90 day study has been carried out in the rabbit with the compound administered dermally twice weekly; CITATION_NUMBERS=[90]; REFERENCE=Ref.: Z Dermal toxicity A 90 day study has been carried out in the rabbit with the compound administered dermally twice weekly; DETAILS_JSON={"cas_number":"106-50-3","citation":"Ref.: Z Dermal toxicity A 90 day study has been carried out in the rabbit with the compound administered dermally twice weekly","dose":"Food intake and body weight gain of treated group were similar to the controls.","duration":"90 day","effect":"r clinical signs considered related to the test article. Food intake and body weight gain of treated group were similar to the controls. At 16 mg/kg bw/d increased incidence of wet chin in both sexes and in wet inguen and/or wet perineum in females was observed. Neuropathology evaluations did not reveal abnormalities within the nervous system or skeletal muscle. There was no effect of the test substance on ocular tissue. The effects observed at 16 mg/kg bw/d are judged as pharmacological responses. Therefore, the NOEL was 8 mg/kg bw/d for both sexes; the NOAEL was 16 mg/kg bw/d. Ref.: Z Dermal toxicity A 90 day study has been carried out in the rabbit with the compound administered dermally twice weekly. Four hair-dye formulation containing 1, 2, 3 or 4% of para-phenylenediamine","endpoint":"","ingredient":"s from temporary tattoos and clothing textiles. PPD is an extreme","loael_value":"","noael_unit":"mg/kg bw/d","noael_value":"8","page":17,"route":"dermal","species":"rabbit","study_id":"sccs_o_094_noael_010"}

sccs_o_094.pdf

SOURCE_SUBDIR=sccs_o_094; REPORT_TITLE=OPINION ON p-Phenylenediamine COLIPA n° A7; OPINION_NUMBER=SCCS/1443/11; COMMITTEE=Scientific Committee on Consumer Safety (SCCS); REPORT_DATE=18 September 2012; VALUE_TEXT=8; DOSE=In this approach, the extrapolated AUC in rats resembling a peroral dosage of 8 mg/kg bw/day (corresponding to the NOAEL) was compared to the AUC in humans following application of a hair dye containing 14C-labelled PPD.; EFFECT=henylenediamine several aspects were taken into account: ¾ The generally accepted approach for systemic toxicity (MOS approach) according to the Notes of Guidance results in a MoS of 200. When toxicokinetic studies are considered, a minimum MoS of 25 can be set. A number of toxicokinetic studies were performed and the applicant proposed to base the safety on the comparison of AUCs (area under curve). In this approach, the extrapolated AUC in rats resembling a peroral dosage of 8 mg/kg bw/day (corresponding to the NOAEL) was compared to the AUC in humans following application of a hair dye containing 14C-labelled PPD. In this case, a safety margin of 23 was obtained which is considered borderline. However, in view of the intermittent exposure and the fact that human exposure through hair dyeing is mainly to N,N’-diacetyl PPD (a non-mutagenic detoxified metabolite), no concern regarding systemic toxicity is raised, when PPD is used in oxidative hair colouring products at on-head concentrations of up to 2.0%. ¾ On the basis of the; CITATION_NUMBERS=[]; DETAILS_JSON={"cas_number":"106-50-3","citation":"","dose":"In this approach, the extrapolated AUC in rats resembling a peroral dosage of 8 mg/kg bw/day (corresponding to the NOAEL) was compared to the AUC in humans following application of a hair dye containing 14C-labelled PPD.","duration":"","effect":"henylenediamine several aspects were taken into account: ¾ The generally accepted approach for systemic toxicity (MOS approach) according to the Notes of Guidance results in a MoS of 200. When toxicokinetic studies are considered, a minimum MoS of 25 can be set. A number of toxicokinetic studies were performed and the applicant proposed to base the safety on the comparison of AUCs (area under curve). In this approach, the extrapolated AUC in rats resembling a peroral dosage of 8 mg/kg bw/day (corresponding to the NOAEL) was compared to the AUC in humans following application of a hair dye containing 14C-labelled PPD. In this case, a safety margin of 23 was obtained which is considered borderline. However, in view of the intermittent exposure and the fact that human exposure through hair dyeing is mainly to N,N’-diacetyl PPD (a non-mutagenic detoxified metabolite), no concern regarding systemic toxicity is raised, when PPD is used in oxidative hair colouring products at on-head concentrations of up to 2.0%. ¾ On the basis of the","endpoint":"","ingredient":"s from temporary tattoos and clothing textiles. PPD is an extreme","loael_value":"","noael_unit":"mg/kg bw/day","noael_value":"8","page":66,"route":"","species":"rat","study_id":"sccs_o_094_noael_047"}

sccs_o_094.pdf

SOURCE_SUBDIR=sccs_o_094; REPORT_TITLE=OPINION ON p-Phenylenediamine COLIPA n° A7; OPINION_NUMBER=SCCS/1443/11; COMMITTEE=Scientific Committee on Consumer Safety (SCCS); REPORT_DATE=18 September 2012; VALUE_TEXT=Gavage NOAEL of 8; EFFECT=Unlabeled table on page 61: Gavage NOAEL of 8 | 22152 | 1415 | 15.6 | 966 | 22.2; CITATION_NUMBERS=[]; DETAILS_JSON={"cas_number":"106-50-3","citation":"","dose":"","duration":"","effect":"Unlabeled table on page 61: Gavage NOAEL of 8 | 22152 | 1415 | 15.6 | 966 | 22.2","endpoint":"","ingredient":"s from temporary tattoos and clothing textiles. PPD is an extreme","loael_value":"","noael_unit":"","noael_value":"Gavage NOAEL of 8","page":61,"route":"oral","species":"","study_id":"sccs_o_094_noael_057"}

sccs_o_094.pdf

SOURCE_SUBDIR=sccs_o_094; REPORT_TITLE=OPINION ON p-Phenylenediamine COLIPA n° A7; OPINION_NUMBER=SCCS/1443/11; COMMITTEE=Scientific Committee on Consumer Safety (SCCS); REPORT_DATE=18 September 2012; VALUE_TEXT=Gavage NOAEL of 8; EFFECT=Unlabeled table on page 61: Gavage NOAEL of 8 | 33038 | 1415 | 23.3 | 966 | 34.2; CITATION_NUMBERS=[]; DETAILS_JSON={"cas_number":"106-50-3","citation":"","dose":"","duration":"","effect":"Unlabeled table on page 61: Gavage NOAEL of 8 | 33038 | 1415 | 23.3 | 966 | 34.2","endpoint":"","ingredient":"s from temporary tattoos and clothing textiles. PPD is an extreme","loael_value":"","noael_unit":"","noael_value":"Gavage NOAEL of 8","page":61,"route":"oral","species":"","study_id":"sccs_o_094_noael_061"}

sccs_o_094.pdf

SOURCE_SUBDIR=sccs_o_094; REPORT_TITLE=OPINION ON p-Phenylenediamine COLIPA n° A7; OPINION_NUMBER=SCCS/1443/11; COMMITTEE=Scientific Committee on Consumer Safety (SCCS); REPORT_DATE=18 September 2012; VALUE_TEXT=unclear:t the relevant human systemic exposure agent after hair dyeing with a [14C]-PPD-containing oxidative hair dye is N,N'-diacetyl-PPD, which is considered a non-toxic metabolite as it is apparently not hydroxylated and has no mutagenic potential in in vitro tests. For the purpose of a toxicokinetic-based margin of safety calculation discussed below, plasma AUC for PPDeq (primarily to the N,N’-diacetylated metabolite) in humans after hair dye use can be compared to plasma AUC in rats at a PPD dose corresponding to the NOAEL. 3.3.10. Photo-induced toxicity 3.3.10.1. Phototoxicity / photoirritation and photosensitisation No data submitted 3.3.10.2. Phototoxicity / photomutagenicity / photoclastogenicity No data submitted 3.3.11. Human data No data submitted 3.3.12. Special investigations No data submitted; DOSE=For the purpose of a toxicokinetic-based margin of safety calculation discussed below, plasma AUC for PPDeq (primarily to the N,N’-diacetylated metabolite) in humans after hair dye use can be compared to plasma AUC in rats at a PPD dose corresponding to the NOAEL.; EFFECT=t the relevant human systemic exposure agent after hair dyeing with a [14C]-PPD-containing oxidative hair dye is N,N'-diacetyl-PPD, which is considered a non-toxic metabolite as it is apparently not hydroxylated and has no mutagenic potential in in vitro tests. For the purpose of a toxicokinetic-based margin of safety calculation discussed below, plasma AUC for PPDeq (primarily to the N,N’-diacetylated metabolite) in humans after hair dye use can be compared to plasma AUC in rats at a PPD dose corresponding to the NOAEL. 3.3.10. Photo-induced toxicity 3.3.10.1. Phototoxicity / photoirritation and photosensitisation No data submitted 3.3.10.2. Phototoxicity / photomutagenicity / photoclastogenicity No data submitted 3.3.11. Human data No data submitted 3.3.12. Special investigations No data submitted; CITATION_NUMBERS=[]; DETAILS_JSON={"cas_number":"106-50-3","citation":"","dose":"For the purpose of a toxicokinetic-based margin of safety calculation discussed below, plasma AUC for PPDeq (primarily to the N,N’-diacetylated metabolite) in humans after hair dye use can be compared to plasma AUC in rats at a PPD dose corresponding to the NOAEL.","duration":"","effect":"t the relevant human systemic exposure agent after hair dyeing with a [14C]-PPD-containing oxidative hair dye is N,N'-diacetyl-PPD, which is considered a non-toxic metabolite as it is apparently not hydroxylated and has no mutagenic potential in in vitro tests. For the purpose of a toxicokinetic-based margin of safety calculation discussed below, plasma AUC for PPDeq (primarily to the N,N’-diacetylated metabolite) in humans after hair dye use can be compared to plasma AUC in rats at a PPD dose corresponding to the NOAEL. 3.3.10. Photo-induced toxicity 3.3.10.1. Phototoxicity / photoirritation and photosensitisation No data submitted 3.3.10.2. Phototoxicity / photomutagenicity / photoclastogenicity No data submitted 3.3.11. Human data No data submitted 3.3.12. Special investigations No data submitted","endpoint":"","ingredient":"s from temporary tattoos and clothing textiles. PPD is an extreme","loael_value":"","noael_unit":"","noael_value":"unclear:t the relevant human systemic exposure agent after hair dyeing with a [14C]-PPD-containing oxidative hair dye is N,N'-diacetyl-PPD, which is considered a non-toxic metabolite as it is apparently not hydroxylated and has no mutagenic potential in in vitro tests. For the purpose of a toxicokinetic-based margin of safety calculation discussed below, plasma AUC for PPDeq (primarily to the N,N’-diacetylated metabolite) in humans after hair dye use can be compared to plasma AUC in rats at a PPD dose corresponding to the NOAEL. 3.3.10. Photo-induced toxicity 3.3.10.1. Phototoxicity / photoirritation and photosensitisation No data submitted 3.3.10.2. Phototoxicity / photomutagenicity / photoclastogenicity No data submitted 3.3.11. Human data No data submitted 3.3.12. Special investigations No data submitted","page":58,"route":"","species":"rat","study_id":"sccs_o_094_noael_014"}

sccs_o_094.pdf

SOURCE_SUBDIR=sccs_o_094; REPORT_TITLE=OPINION ON p-Phenylenediamine COLIPA n° A7; OPINION_NUMBER=SCCS/1443/11; COMMITTEE=Scientific Committee on Consumer Safety (SCCS); REPORT_DATE=18 September 2012; VALUE_TEXT=16; DOSE=ed liver weights were significantly increased for males given 8 mg/kg bw/day and 16 mg/kg bw/day.; EFFECT=ed liver weights were significantly increased for males given 8 mg/kg bw/day and 16 mg/kg bw/day. At the same dose levels, absolute and body weight-related kidney weights were increased for females. However, no associated histopathological changes were noted. No treatment macroscopic or microscopic findings were recorded. Histopathological examination restricted significant finding to minimal myodegeneration on skeletal muscle on 1 male and 1 female of the high dose group (16 mg/kg bw). Based on these results, the NOEL of PPD was established at 4 mg/kg bw/day by the applicant and considered as NOAEL by the SCCNFP and SCCP. Ref.: 121 External expert review (18, subm V) In the expert review, it was stated that the liver and kidney weight increases at 8 and 16 mg/kg bw/d are the only changes in this study which were considered to be related to treatment with PPD. Such organ weight changes without associated clinical chemistry; CITATION=Ref.: 121 External expert review (18, subm V) In the expert review, it was stated that the liver and kidney weight increases at 8 and 16 mg/kg bw/d are the only changes in this study whi; CITATION_NUMBERS=[121,18,8,16]; REFERENCE=Ref.: 121 External expert review (18, subm V) In the expert review, it was stated that the liver and kidney weight increases at 8 and 16 mg/kg bw/d are the only changes in this study whi; DETAILS_JSON={"cas_number":"106-50-3","citation":"Ref.: 121 External expert review (18, subm V) In the expert review, it was stated that the liver and kidney weight increases at 8 and 16 mg/kg bw/d are the only changes in this study whi","dose":"ed liver weights were significantly increased for males given 8 mg/kg bw/day and 16 mg/kg bw/day.","duration":"","effect":"ed liver weights were significantly increased for males given 8 mg/kg bw/day and 16 mg/kg bw/day. At the same dose levels, absolute and body weight-related kidney weights were increased for females. However, no associated histopathological changes were noted. No treatment macroscopic or microscopic findings were recorded. Histopathological examination restricted significant finding to minimal myodegeneration on skeletal muscle on 1 male and 1 female of the high dose group (16 mg/kg bw). Based on these results, the NOEL of PPD was established at 4 mg/kg bw/day by the applicant and considered as NOAEL by the SCCNFP and SCCP. Ref.: 121 External expert review (18, subm V) In the expert review, it was stated that the liver and kidney weight increases at 8 and 16 mg/kg bw/d are the only changes in this study which were considered to be related to treatment with PPD. Such organ weight changes without associated clinical chemistry","endpoint":"","ingredient":"s from temporary tattoos and clothing textiles. PPD is an extreme","loael_value":"","noael_unit":"mg/kg bw","noael_value":"16","page":16,"route":"","species":"","study_id":"sccs_o_094_noael_003"}

sccs_o_094.pdf

SOURCE_SUBDIR=sccs_o_094; REPORT_TITLE=OPINION ON p-Phenylenediamine COLIPA n° A7; OPINION_NUMBER=SCCS/1443/11; COMMITTEE=Scientific Committee on Consumer Safety (SCCS); REPORT_DATE=18 September 2012; VALUE_TEXT=16; DOSE=The external expert therefore concluded the following for this study: • The no observed effect level (NOEL) is 4 mg/kg bw/d • The no observed adverse effect level (NOAEL) is 16 mg/kg bw/d This conclusion confirmed the NOEL as cited in the original report.; EFFECT=SCCS/1443/11 Opinion on p-phenylenediamine ___________________________________________________________________________________________ 17 alterations and without any corresponding histopathological changes were considered to be adaptive in nature and non-adverse. The external expert therefore concluded the following for this study: • The no observed effect level (NOEL) is 4 mg/kg bw/d • The no observed adverse effect level (NOAEL) is 16 mg/kg bw/d This conclusion confirmed the NOEL as cited in the original report. It also expanded this original conclusion to include a judgement on adverse findings and defined the NOAEL for the study. Comment of the SCCS The SCCS agrees to this judgement of kidney and liver effects observed. However, also the observed myodegenerative effects need to be considered. It is well known that PPD and some substituted derivatives can induce myotoxicity (e.g. even after 3 days of administration of 36.2 mg/kg bw, s; CITATION_NUMBERS=[]; DETAILS_JSON={"cas_number":"106-50-3","citation":"","dose":"The external expert therefore concluded the following for this study: • The no observed effect level (NOEL) is 4 mg/kg bw/d • The no observed adverse effect level (NOAEL) is 16 mg/kg bw/d This conclusion confirmed the NOEL as cited in the original report.","duration":"3 days","effect":"SCCS/1443/11 Opinion on p-phenylenediamine ___________________________________________________________________________________________ 17 alterations and without any corresponding histopathological changes were considered to be adaptive in nature and non-adverse. The external expert therefore concluded the following for this study: • The no observed effect level (NOEL) is 4 mg/kg bw/d • The no observed adverse effect level (NOAEL) is 16 mg/kg bw/d This conclusion confirmed the NOEL as cited in the original report. It also expanded this original conclusion to include a judgement on adverse findings and defined the NOAEL for the study. Comment of the SCCS The SCCS agrees to this judgement of kidney and liver effects observed. However, also the observed myodegenerative effects need to be considered. It is well known that PPD and some substituted derivatives can induce myotoxicity (e.g. even after 3 days of administration of 36.2 mg/kg bw, s","endpoint":"","ingredient":"s from temporary tattoos and clothing textiles. PPD is an extreme","loael_value":"","noael_unit":"mg/kg bw/d","noael_value":"16","page":17,"route":"","species":"","study_id":"sccs_o_094_noael_006"}

sccs_o_094.pdf

SOURCE_SUBDIR=sccs_o_094; REPORT_TITLE=OPINION ON p-Phenylenediamine COLIPA n° A7; OPINION_NUMBER=SCCS/1443/11; COMMITTEE=Scientific Committee on Consumer Safety (SCCS); REPORT_DATE=18 September 2012; VALUE_TEXT=16; DOSE=The external expert therefore concluded the following for this study: • The no observed effect level (NOEL) is 4 mg/kg bw/d • The no observed adverse effect level (NOAEL) is 16 mg/kg bw/d This conclusion confirmed the NOEL as cited in the original report.; EFFECT=______________________________ 17 alterations and without any corresponding histopathological changes were considered to be adaptive in nature and non-adverse. The external expert therefore concluded the following for this study: • The no observed effect level (NOEL) is 4 mg/kg bw/d • The no observed adverse effect level (NOAEL) is 16 mg/kg bw/d This conclusion confirmed the NOEL as cited in the original report. It also expanded this original conclusion to include a judgement on adverse findings and defined the NOAEL for the study. Comment of the SCCS The SCCS agrees to this judgement of kidney and liver effects observed. However, also the observed myodegenerative effects need to be considered. It is well known that PPD and some substituted derivatives can induce myotoxicity (e.g. even after 3 days of administration of 36.2 mg/kg bw, see Additional References H and I: Munday et al. 1990; Munday, Manns 1999). This myodegeneration in the skeletal muscle was also noted in the 28-day study in 3 females given 40 mg/kg bw/d (Ref. 1; CITATION_NUMBERS=[]; DETAILS_JSON={"cas_number":"106-50-3","citation":"","dose":"The external expert therefore concluded the following for this study: • The no observed effect level (NOEL) is 4 mg/kg bw/d • The no observed adverse effect level (NOAEL) is 16 mg/kg bw/d This conclusion confirmed the NOEL as cited in the original report.","duration":"3 days","effect":"______________________________ 17 alterations and without any corresponding histopathological changes were considered to be adaptive in nature and non-adverse. The external expert therefore concluded the following for this study: • The no observed effect level (NOEL) is 4 mg/kg bw/d • The no observed adverse effect level (NOAEL) is 16 mg/kg bw/d This conclusion confirmed the NOEL as cited in the original report. It also expanded this original conclusion to include a judgement on adverse findings and defined the NOAEL for the study. Comment of the SCCS The SCCS agrees to this judgement of kidney and liver effects observed. However, also the observed myodegenerative effects need to be considered. It is well known that PPD and some substituted derivatives can induce myotoxicity (e.g. even after 3 days of administration of 36.2 mg/kg bw, see Additional References H and I: Munday et al. 1990; Munday, Manns 1999). This myodegeneration in the skeletal muscle was also noted in the 28-day study in 3 females given 40 mg/kg bw/d (Ref. 1","endpoint":"","ingredient":"s from temporary tattoos and clothing textiles. PPD is an extreme","loael_value":"","noael_unit":"mg/kg bw/d","noael_value":"16","page":17,"route":"","species":"","study_id":"sccs_o_094_noael_007"}

sccs_o_094.pdf

SOURCE_SUBDIR=sccs_o_094; REPORT_TITLE=OPINION ON p-Phenylenediamine COLIPA n° A7; OPINION_NUMBER=SCCS/1443/11; COMMITTEE=Scientific Committee on Consumer Safety (SCCS); REPORT_DATE=18 September 2012; VALUE_TEXT=16; DOSE=Food intake and body weight gain of treated group were similar to the controls.; EFFECT=test article. Food intake and body weight gain of treated group were similar to the controls. At 16 mg/kg bw/d increased incidence of wet chin in both sexes and in wet inguen and/or wet perineum in females was observed. Neuropathology evaluations did not reveal abnormalities within the nervous system or skeletal muscle. There was no effect of the test substance on ocular tissue. The effects observed at 16 mg/kg bw/d are judged as pharmacological responses. Therefore, the NOEL was 8 mg/kg bw/d for both sexes; the NOAEL was 16 mg/kg bw/d. Ref.: Z Dermal toxicity A 90 day study has been carried out in the rabbit with the compound administered dermally twice weekly. Four hair-dye formulation containing 1, 2, 3 or 4% of para-phenylenediamine; CITATION=Ref.: Z Dermal toxicity A 90 day study has been carried out in the rabbit with the compound administered dermally twice weekly; CITATION_NUMBERS=[90]; REFERENCE=Ref.: Z Dermal toxicity A 90 day study has been carried out in the rabbit with the compound administered dermally twice weekly; DETAILS_JSON={"cas_number":"106-50-3","citation":"Ref.: Z Dermal toxicity A 90 day study has been carried out in the rabbit with the compound administered dermally twice weekly","dose":"Food intake and body weight gain of treated group were similar to the controls.","duration":"90 day","effect":"test article. Food intake and body weight gain of treated group were similar to the controls. At 16 mg/kg bw/d increased incidence of wet chin in both sexes and in wet inguen and/or wet perineum in females was observed. Neuropathology evaluations did not reveal abnormalities within the nervous system or skeletal muscle. There was no effect of the test substance on ocular tissue. The effects observed at 16 mg/kg bw/d are judged as pharmacological responses. Therefore, the NOEL was 8 mg/kg bw/d for both sexes; the NOAEL was 16 mg/kg bw/d. Ref.: Z Dermal toxicity A 90 day study has been carried out in the rabbit with the compound administered dermally twice weekly. Four hair-dye formulation containing 1, 2, 3 or 4% of para-phenylenediamine","endpoint":"","ingredient":"s from temporary tattoos and clothing textiles. PPD is an extreme","loael_value":"","noael_unit":"mg/kg bw/d","noael_value":"16","page":17,"route":"dermal","species":"rabbit","study_id":"sccs_o_094_noael_011"}

sccs_o_094.pdf

SOURCE_SUBDIR=sccs_o_094; REPORT_TITLE=OPINION ON p-Phenylenediamine COLIPA n° A7; OPINION_NUMBER=SCCS/1443/11; COMMITTEE=Scientific Committee on Consumer Safety (SCCS); REPORT_DATE=18 September 2012; VALUE_TEXT=16; DOSE=In the recent submission of 2011, the applicant, based on the expert review of the 90 days toxicity study, proposed that 4 mg/kg bw/d should be considered as a NOEL and not as a NOAEL, as the increase in body-weight related liver and kidney weights observed were considered mild modifications, not associated with histopathological or clinical pat...; EFFECT=in 77. The applicant proposed to base the safety on the comparison of AUCs (area under curve) described below. In the recent submission of 2011, the applicant, based on the expert review of the 90 days toxicity study, proposed that 4 mg/kg bw/d should be considered as a NOEL and not as a NOAEL, as the increase in body-weight related liver and kidney weights observed were considered mild modifications, not associated with histopathological or clinical pathology changes and adaptive, thus non–adverse. Therefore, the NOAEL from this study should then be 16 mg/kg bw/d (the highest dose tested). The SCCS agrees to this judgement of kidney and liver effects observed and that in the 90 days toxicity study, 4 mg/kg bw/d could be considered as a NOEL instead of a NOAEL for these effects. The increase in body-weight related liver and kidney weights at the dose of 8 and 16 mg/kg bw/d, even if statistically significant remains still slight. Moreover they were not associated with histopathological changes or clinical chemistry alterations. Ho; CITATION_NUMBERS=[]; DETAILS_JSON={"cas_number":"106-50-3","citation":"","dose":"In the recent submission of 2011, the applicant, based on the expert review of the 90 days toxicity study, proposed that 4 mg/kg bw/d should be considered as a NOEL and not as a NOAEL, as the increase in body-weight related liver and kidney weights observed were considered mild modifications, not associated with histopathological or clinical pat...","duration":"90 days","effect":"in 77. The applicant proposed to base the safety on the comparison of AUCs (area under curve) described below. In the recent submission of 2011, the applicant, based on the expert review of the 90 days toxicity study, proposed that 4 mg/kg bw/d should be considered as a NOEL and not as a NOAEL, as the increase in body-weight related liver and kidney weights observed were considered mild modifications, not associated with histopathological or clinical pathology changes and adaptive, thus non–adverse. Therefore, the NOAEL from this study should then be 16 mg/kg bw/d (the highest dose tested). The SCCS agrees to this judgement of kidney and liver effects observed and that in the 90 days toxicity study, 4 mg/kg bw/d could be considered as a NOEL instead of a NOAEL for these effects. The increase in body-weight related liver and kidney weights at the dose of 8 and 16 mg/kg bw/d, even if statistically significant remains still slight. Moreover they were not associated with histopathological changes or clinical chemistry alterations. Ho","endpoint":"","ingredient":"s from temporary tattoos and clothing textiles. PPD is an extreme","loael_value":"","noael_unit":"mg/kg bw/d","noael_value":"16","page":59,"route":"","species":"","study_id":"sccs_o_094_noael_018"}

sccs_o_094.pdf

SOURCE_SUBDIR=sccs_o_094; REPORT_TITLE=OPINION ON p-Phenylenediamine COLIPA n° A7; OPINION_NUMBER=SCCS/1443/11; COMMITTEE=Scientific Committee on Consumer Safety (SCCS); REPORT_DATE=18 September 2012; VALUE_TEXT=16; DOSE=in the recent dossier it was argued that liver and kidney weight increases at 8 and 16 mg/kg bw/d are the only changes in this study which are considered to be related to treatment with PPD.; EFFECT=in the recent dossier it was argued that liver and kidney weight increases at 8 and 16 mg/kg bw/d are the only changes in this study which are considered to be related to treatment with PPD. Such organ weight changes without associated clinical chemistry alterations and without any corresponding histopathological changes were considered to be adaptive in nature and non-adverse. The applicant concluded for this study that the no observed effect level (NOEL) is 4 mg/kg bw/d and the no observed adverse effect level (NOAEL) is 16 mg/kg bw/d. The SCCS agrees to this judgement of kidney and liver effects observed. However, myodegenerative effects also need to be considered. It is well known that PPD and some substituted derivatives can induce myotoxicity (e.g. even after 3 days of administration of 36.2 mg/kg bw, see Ref. I). This myodegeneration in the skeletal muscle was also noted in the 28-day study in 3 females given 40 mg/kg bw/d (Ref. 120). Minimal myodegeneration; CITATION=(Ref. 120); CITATION_NUMBERS=[120]; REFERENCE=(Ref. 120); DETAILS_JSON={"cas_number":"106-50-3","citation":"(Ref. 120)","dose":"in the recent dossier it was argued that liver and kidney weight increases at 8 and 16 mg/kg bw/d are the only changes in this study which are considered to be related to treatment with PPD.","duration":"3 days","effect":"in the recent dossier it was argued that liver and kidney weight increases at 8 and 16 mg/kg bw/d are the only changes in this study which are considered to be related to treatment with PPD. Such organ weight changes without associated clinical chemistry alterations and without any corresponding histopathological changes were considered to be adaptive in nature and non-adverse. The applicant concluded for this study that the no observed effect level (NOEL) is 4 mg/kg bw/d and the no observed adverse effect level (NOAEL) is 16 mg/kg bw/d. The SCCS agrees to this judgement of kidney and liver effects observed. However, myodegenerative effects also need to be considered. It is well known that PPD and some substituted derivatives can induce myotoxicity (e.g. even after 3 days of administration of 36.2 mg/kg bw, see Ref. I). This myodegeneration in the skeletal muscle was also noted in the 28-day study in 3 females given 40 mg/kg bw/d (Ref. 120). Minimal myodegeneration","endpoint":"","ingredient":"s from temporary tattoos and clothing textiles. PPD is an extreme","loael_value":"","noael_unit":"mg/kg bw/d","noael_value":"16","page":62,"route":"","species":"","study_id":"sccs_o_094_noael_039"}

sccs_o_094.pdf

SOURCE_SUBDIR=sccs_o_094; REPORT_TITLE=OPINION ON p-Phenylenediamine COLIPA n° A7; OPINION_NUMBER=SCCS/1443/11; COMMITTEE=Scientific Committee on Consumer Safety (SCCS); REPORT_DATE=18 September 2012; VALUE_TEXT=Gavage NOAEL of 16; EFFECT=Unlabeled table on page 61: Gavage NOAEL of 16 | 44304 | 1415 | 31.3 | 966 | 45.9; CITATION_NUMBERS=[]; DETAILS_JSON={"cas_number":"106-50-3","citation":"","dose":"","duration":"","effect":"Unlabeled table on page 61: Gavage NOAEL of 16 | 44304 | 1415 | 31.3 | 966 | 45.9","endpoint":"","ingredient":"s from temporary tattoos and clothing textiles. PPD is an extreme","loael_value":"","noael_unit":"","noael_value":"Gavage NOAEL of 16","page":61,"route":"oral","species":"","study_id":"sccs_o_094_noael_058"}

sccs_o_094.pdf

SOURCE_SUBDIR=sccs_o_094; REPORT_TITLE=OPINION ON p-Phenylenediamine COLIPA n° A7; OPINION_NUMBER=SCCS/1443/11; COMMITTEE=Scientific Committee on Consumer Safety (SCCS); REPORT_DATE=18 September 2012; VALUE_TEXT=Gavage NOAEL of 16; EFFECT=Unlabeled table on page 61: Gavage NOAEL of 16 | 66076 | 1415 | 46.7 | 966 | 68.4; CITATION_NUMBERS=[]; DETAILS_JSON={"cas_number":"106-50-3","citation":"","dose":"","duration":"","effect":"Unlabeled table on page 61: Gavage NOAEL of 16 | 66076 | 1415 | 46.7 | 966 | 68.4","endpoint":"","ingredient":"s from temporary tattoos and clothing textiles. PPD is an extreme","loael_value":"","noael_unit":"","noael_value":"Gavage NOAEL of 16","page":61,"route":"oral","species":"","study_id":"sccs_o_094_noael_062"}

sccs_o_094.pdf

SOURCE_SUBDIR=sccs_o_094; REPORT_TITLE=OPINION ON p-Phenylenediamine COLIPA n° A7; OPINION_NUMBER=SCCS/1443/11; COMMITTEE=Scientific Committee on Consumer Safety (SCCS); REPORT_DATE=18 September 2012; VALUE_TEXT=50; DOSE=PPD administered in the diet at concentrations of 0.05, 0.1, 0.2 and 0.4% (or approximately 25, 50, 100 and 200 mg/kg bw/day respectively).; EFFECT=PPD administered in the diet at concentrations of 0.05, 0.1, 0.2 and 0.4% (or approximately 25, 50, 100 and 200 mg/kg bw/day respectively). Mortalities were observed at the theoretical dose of 200 mg/kg bw in 9 male rats and in 1 female rat. At the same dose level, a 50% reduction in body weight in both sexes as compared to controls, as well as increased relative liver and kidney weights were noted. A trend toward these above observations was noted at the theoretical dose 100 mg/kg bw. Based on these results, the NOAEL was obtained with dosing 50 mg/kg bw. Ref.: 53 Another 13-week neurotoxicity study has been performed via gavage in young adult F344 strain rats to evaluate the potential neurotoxicity of PPD. Male and female ccl:CD BR Rats (10 rats/sex/group) were administered PPD at doses of 4, 8 and 16 mg/kg bw/day while the control group received the vehicle only (sterile water for injection). All doses were given under a same dosage volume of 10 ml/kg bw. The animals were examined daily for mortality and clinical signs. Food; CITATION=Ref.: 53 Another 13-week neurotoxicity study has been performed via gavage in young adult F344 strain rats to evaluate the potential neurotoxicity of PPD; CITATION_NUMBERS=[53,13,344]; REFERENCE=Ref.: 53 Another 13-week neurotoxicity study has been performed via gavage in young adult F344 strain rats to evaluate the potential neurotoxicity of PPD; DETAILS_JSON={"cas_number":"106-50-3","citation":"Ref.: 53 Another 13-week neurotoxicity study has been performed via gavage in young adult F344 strain rats to evaluate the potential neurotoxicity of PPD","dose":"PPD administered in the diet at concentrations of 0.05, 0.1, 0.2 and 0.4% (or approximately 25, 50, 100 and 200 mg/kg bw/day respectively).","duration":"13-week","effect":"PPD administered in the diet at concentrations of 0.05, 0.1, 0.2 and 0.4% (or approximately 25, 50, 100 and 200 mg/kg bw/day respectively). Mortalities were observed at the theoretical dose of 200 mg/kg bw in 9 male rats and in 1 female rat. At the same dose level, a 50% reduction in body weight in both sexes as compared to controls, as well as increased relative liver and kidney weights were noted. A trend toward these above observations was noted at the theoretical dose 100 mg/kg bw. Based on these results, the NOAEL was obtained with dosing 50 mg/kg bw. Ref.: 53 Another 13-week neurotoxicity study has been performed via gavage in young adult F344 strain rats to evaluate the potential neurotoxicity of PPD. Male and female ccl:CD BR Rats (10 rats/sex/group) were administered PPD at doses of 4, 8 and 16 mg/kg bw/day while the control group received the vehicle only (sterile water for injection). All doses were given under a same dosage volume of 10 ml/kg bw. The animals were examined daily for mortality and clinical signs. Food","endpoint":"","ingredient":"s from temporary tattoos and clothing textiles. PPD is an extreme","loael_value":"","noael_unit":"mg/kg bw","noael_value":"50","page":17,"route":"oral","species":"rat","study_id":"sccs_o_094_noael_009"}

sccs_o_094.pdf

SOURCE_SUBDIR=sccs_o_094; REPORT_TITLE=OPINION ON p-Phenylenediamine COLIPA n° A7; OPINION_NUMBER=SCCS/1443/11; COMMITTEE=Scientific Committee on Consumer Safety (SCCS); REPORT_DATE=18 September 2012; VALUE_TEXT=Dietary NOEL of 50; EFFECT=Unlabeled table on page 61: Dietary NOEL of 50 | 138450 | 1415 | 97.8 | 966 | 143.3; CITATION_NUMBERS=[]; DETAILS_JSON={"cas_number":"106-50-3","citation":"","dose":"","duration":"","effect":"Unlabeled table on page 61: Dietary NOEL of 50 | 138450 | 1415 | 97.8 | 966 | 143.3","endpoint":"","ingredient":"s from temporary tattoos and clothing textiles. PPD is an extreme","loael_value":"","noael_unit":"","noael_value":"Dietary NOEL of 50","page":61,"route":"oral","species":"","study_id":"sccs_o_094_noael_059"}

sccs_o_094.pdf

SOURCE_SUBDIR=sccs_o_094; REPORT_TITLE=OPINION ON p-Phenylenediamine COLIPA n° A7; OPINION_NUMBER=SCCS/1443/11; COMMITTEE=Scientific Committee on Consumer Safety (SCCS); REPORT_DATE=18 September 2012; VALUE_TEXT=Dietary NOEL of 50; EFFECT=Unlabeled table on page 61: Dietary NOEL of 50 | 206488 | 1415 | 145.9 | 966 | 213.8; CITATION_NUMBERS=[]; DETAILS_JSON={"cas_number":"106-50-3","citation":"","dose":"","duration":"","effect":"Unlabeled table on page 61: Dietary NOEL of 50 | 206488 | 1415 | 145.9 | 966 | 213.8","endpoint":"","ingredient":"s from temporary tattoos and clothing textiles. PPD is an extreme","loael_value":"","noael_unit":"","noael_value":"Dietary NOEL of 50","page":61,"route":"oral","species":"","study_id":"sccs_o_094_noael_063"}

sccs_o_094.pdf

SOURCE_SUBDIR=sccs_o_094; REPORT_TITLE=OPINION ON p-Phenylenediamine COLIPA n° A7; OPINION_NUMBER=SCCS/1443/11; COMMITTEE=Scientific Committee on Consumer Safety (SCCS); REPORT_DATE=18 September 2012; VALUE_TEXT=unclear:Unlabeled table on page 61: Gavage dose of 4 (NOAEL used by the SCCP) | 11076 | 1415 | 7.8 | 966 | 11.5; DOSE=Gavage dose of 4 (NOAEL used by the SCCP) | 11076 | 1415 | 7.8 | 966 | 11.5; EFFECT=Unlabeled table on page 61: Gavage dose of 4 (NOAEL used by the SCCP) | 11076 | 1415 | 7.8 | 966 | 11.5; CITATION_NUMBERS=[]; DETAILS_JSON={"cas_number":"106-50-3","citation":"","dose":"Gavage dose of 4 (NOAEL used by the SCCP) | 11076 | 1415 | 7.8 | 966 | 11.5","duration":"","effect":"Unlabeled table on page 61: Gavage dose of 4 (NOAEL used by the SCCP) | 11076 | 1415 | 7.8 | 966 | 11.5","endpoint":"","ingredient":"s from temporary tattoos and clothing textiles. PPD is an extreme","loael_value":"","noael_unit":"","noael_value":"unclear:Unlabeled table on page 61: Gavage dose of 4 (NOAEL used by the SCCP) | 11076 | 1415 | 7.8 | 966 | 11.5","page":61,"route":"oral","species":"","study_id":"sccs_o_094_noael_048"}

sccs_o_094.pdf

SOURCE_SUBDIR=sccs_o_094; REPORT_TITLE=OPINION ON p-Phenylenediamine COLIPA n° A7; OPINION_NUMBER=SCCS/1443/11; COMMITTEE=Scientific Committee on Consumer Safety (SCCS); REPORT_DATE=18 September 2012; VALUE_TEXT=unclear:Unlabeled table on page 61: Gavage NOAEL of 8 | 22152 | 1415 | 15.6 | 966 | 22.2; EFFECT=Unlabeled table on page 61: Gavage NOAEL of 8 | 22152 | 1415 | 15.6 | 966 | 22.2; CITATION_NUMBERS=[]; DETAILS_JSON={"cas_number":"106-50-3","citation":"","dose":"","duration":"","effect":"Unlabeled table on page 61: Gavage NOAEL of 8 | 22152 | 1415 | 15.6 | 966 | 22.2","endpoint":"","ingredient":"s from temporary tattoos and clothing textiles. PPD is an extreme","loael_value":"","noael_unit":"","noael_value":"unclear:Unlabeled table on page 61: Gavage NOAEL of 8 | 22152 | 1415 | 15.6 | 966 | 22.2","page":61,"route":"oral","species":"","study_id":"sccs_o_094_noael_049"}

sccs_o_094.pdf

SOURCE_SUBDIR=sccs_o_094; REPORT_TITLE=OPINION ON p-Phenylenediamine COLIPA n° A7; OPINION_NUMBER=SCCS/1443/11; COMMITTEE=Scientific Committee on Consumer Safety (SCCS); REPORT_DATE=18 September 2012; VALUE_TEXT=unclear:Unlabeled table on page 61: Gavage NOAEL of 16 | 44304 | 1415 | 31.3 | 966 | 45.9; EFFECT=Unlabeled table on page 61: Gavage NOAEL of 16 | 44304 | 1415 | 31.3 | 966 | 45.9; CITATION_NUMBERS=[]; DETAILS_JSON={"cas_number":"106-50-3","citation":"","dose":"","duration":"","effect":"Unlabeled table on page 61: Gavage NOAEL of 16 | 44304 | 1415 | 31.3 | 966 | 45.9","endpoint":"","ingredient":"s from temporary tattoos and clothing textiles. PPD is an extreme","loael_value":"","noael_unit":"","noael_value":"unclear:Unlabeled table on page 61: Gavage NOAEL of 16 | 44304 | 1415 | 31.3 | 966 | 45.9","page":61,"route":"oral","species":"","study_id":"sccs_o_094_noael_050"}

sccs_o_094.pdf

SOURCE_SUBDIR=sccs_o_094; REPORT_TITLE=OPINION ON p-Phenylenediamine COLIPA n° A7; OPINION_NUMBER=SCCS/1443/11; COMMITTEE=Scientific Committee on Consumer Safety (SCCS); REPORT_DATE=18 September 2012; VALUE_TEXT=unclear:Unlabeled table on page 61: Dietary NOEL of 50 | 138450 | 1415 | 97.8 | 966 | 143.3; EFFECT=Unlabeled table on page 61: Dietary NOEL of 50 | 138450 | 1415 | 97.8 | 966 | 143.3; CITATION_NUMBERS=[]; DETAILS_JSON={"cas_number":"106-50-3","citation":"","dose":"","duration":"","effect":"Unlabeled table on page 61: Dietary NOEL of 50 | 138450 | 1415 | 97.8 | 966 | 143.3","endpoint":"","ingredient":"s from temporary tattoos and clothing textiles. PPD is an extreme","loael_value":"","noael_unit":"","noael_value":"unclear:Unlabeled table on page 61: Dietary NOEL of 50 | 138450 | 1415 | 97.8 | 966 | 143.3","page":61,"route":"oral","species":"","study_id":"sccs_o_094_noael_051"}

sccs_o_094.pdf

SOURCE_SUBDIR=sccs_o_094; REPORT_TITLE=OPINION ON p-Phenylenediamine COLIPA n° A7; OPINION_NUMBER=SCCS/1443/11; COMMITTEE=Scientific Committee on Consumer Safety (SCCS); REPORT_DATE=18 September 2012; VALUE_TEXT=unclear:Unlabeled table on page 61: Gavage dose of 4 (NOAEL used by the SCCP) | 16519 | 1415 | 11.6 | 966 | 17.1; DOSE=Gavage dose of 4 (NOAEL used by the SCCP) | 16519 | 1415 | 11.6 | 966 | 17.1; EFFECT=Unlabeled table on page 61: Gavage dose of 4 (NOAEL used by the SCCP) | 16519 | 1415 | 11.6 | 966 | 17.1; CITATION_NUMBERS=[]; DETAILS_JSON={"cas_number":"106-50-3","citation":"","dose":"Gavage dose of 4 (NOAEL used by the SCCP) | 16519 | 1415 | 11.6 | 966 | 17.1","duration":"","effect":"Unlabeled table on page 61: Gavage dose of 4 (NOAEL used by the SCCP) | 16519 | 1415 | 11.6 | 966 | 17.1","endpoint":"","ingredient":"s from temporary tattoos and clothing textiles. PPD is an extreme","loael_value":"","noael_unit":"","noael_value":"unclear:Unlabeled table on page 61: Gavage dose of 4 (NOAEL used by the SCCP) | 16519 | 1415 | 11.6 | 966 | 17.1","page":61,"route":"oral","species":"","study_id":"sccs_o_094_noael_052"}

sccs_o_094.pdf

SOURCE_SUBDIR=sccs_o_094; REPORT_TITLE=OPINION ON p-Phenylenediamine COLIPA n° A7; OPINION_NUMBER=SCCS/1443/11; COMMITTEE=Scientific Committee on Consumer Safety (SCCS); REPORT_DATE=18 September 2012; VALUE_TEXT=unclear:Unlabeled table on page 61: Gavage NOAEL of 8 | 33038 | 1415 | 23.3 | 966 | 34.2; EFFECT=Unlabeled table on page 61: Gavage NOAEL of 8 | 33038 | 1415 | 23.3 | 966 | 34.2; CITATION_NUMBERS=[]; DETAILS_JSON={"cas_number":"106-50-3","citation":"","dose":"","duration":"","effect":"Unlabeled table on page 61: Gavage NOAEL of 8 | 33038 | 1415 | 23.3 | 966 | 34.2","endpoint":"","ingredient":"s from temporary tattoos and clothing textiles. PPD is an extreme","loael_value":"","noael_unit":"","noael_value":"unclear:Unlabeled table on page 61: Gavage NOAEL of 8 | 33038 | 1415 | 23.3 | 966 | 34.2","page":61,"route":"oral","species":"","study_id":"sccs_o_094_noael_053"}

sccs_o_094.pdf

SOURCE_SUBDIR=sccs_o_094; REPORT_TITLE=OPINION ON p-Phenylenediamine COLIPA n° A7; OPINION_NUMBER=SCCS/1443/11; COMMITTEE=Scientific Committee on Consumer Safety (SCCS); REPORT_DATE=18 September 2012; VALUE_TEXT=unclear:Unlabeled table on page 61: Gavage NOAEL of 16 | 66076 | 1415 | 46.7 | 966 | 68.4; EFFECT=Unlabeled table on page 61: Gavage NOAEL of 16 | 66076 | 1415 | 46.7 | 966 | 68.4; CITATION_NUMBERS=[]; DETAILS_JSON={"cas_number":"106-50-3","citation":"","dose":"","duration":"","effect":"Unlabeled table on page 61: Gavage NOAEL of 16 | 66076 | 1415 | 46.7 | 966 | 68.4","endpoint":"","ingredient":"s from temporary tattoos and clothing textiles. PPD is an extreme","loael_value":"","noael_unit":"","noael_value":"unclear:Unlabeled table on page 61: Gavage NOAEL of 16 | 66076 | 1415 | 46.7 | 966 | 68.4","page":61,"route":"oral","species":"","study_id":"sccs_o_094_noael_054"}

sccs_o_094.pdf

SOURCE_SUBDIR=sccs_o_094; REPORT_TITLE=OPINION ON p-Phenylenediamine COLIPA n° A7; OPINION_NUMBER=SCCS/1443/11; COMMITTEE=Scientific Committee on Consumer Safety (SCCS); REPORT_DATE=18 September 2012; VALUE_TEXT=unclear:Unlabeled table on page 61: Dietary NOEL of 50 | 206488 | 1415 | 145.9 | 966 | 213.8; EFFECT=Unlabeled table on page 61: Dietary NOEL of 50 | 206488 | 1415 | 145.9 | 966 | 213.8; CITATION_NUMBERS=[]; DETAILS_JSON={"cas_number":"106-50-3","citation":"","dose":"","duration":"","effect":"Unlabeled table on page 61: Dietary NOEL of 50 | 206488 | 1415 | 145.9 | 966 | 213.8","endpoint":"","ingredient":"s from temporary tattoos and clothing textiles. PPD is an extreme","loael_value":"","noael_unit":"","noael_value":"unclear:Unlabeled table on page 61: Dietary NOEL of 50 | 206488 | 1415 | 145.9 | 966 | 213.8","page":61,"route":"oral","species":"","study_id":"sccs_o_094_noael_055"}

sccs_o_094.pdf

{"dose":"For the calculation of the MoS, a NOAEL of 4 mg/kg bw/d was used.","effect":"SCCS/1443/11 Opinion on p-phenylenediamine ___________________________________________________________________________________________ 59 3.3.13. Safety evaluation (including calculation of the MoS) • Evaluation based on Margin of Safety (MoS) In 2006 the SCCP concluded that, based on the classical MoS approach, the safety of p- phenylenediamine used as an oxidative hair dye at an applied concentration of 2% could not be warranted. For the calculation of the MoS, a NOAEL of 4 mg/kg bw/d was used. This NOAEL was derived from a 90 days oral toxicity study in which mean absolute and body- weight related liver and kidney weights were significantly increased for males and females, at 8 mg/kg bw/d and 16 mg/kg bw/d respectively, and minimal myodegeneration on skeletal muscle were observed in one male and one female of the high dose group. The MoS resulted in 77. The applicant proposed to base the safety on the comparison of AUCs (area under curve) described below. In the recent submissi","page":59,"pdf":"sccs_o_094.pdf","row_type":"noael_study","study_id":"sccs_o_094_noael_015"}

sccs_o_094.pdf

{"dose":"For the calculation of the MoS, a NOAEL of 4 mg/kg bw/d was used.","effect":"SCCS/1443/11 Opinion on p-phenylenediamine ___________________________________________________________________________________________ 59 3.3.13. Safety evaluation (including calculation of the MoS) • Evaluation based on Margin of Safety (MoS) In 2006 the SCCP concluded that, based on the classical MoS approach, the safety of p- phenylenediamine used as an oxidative hair dye at an applied concentration of 2% could not be warranted. For the calculation of the MoS, a NOAEL of 4 mg/kg bw/d was used. This NOAEL was derived from a 90 days oral toxicity study in which mean absolute and body- weight related liver and kidney weights were significantly increased for males and females, at 8 mg/kg bw/d and 16 mg/kg bw/d respectively, and minimal myodegeneration on skeletal muscle were observed in one male and one female of the high dose group. The MoS resulted in 77. The applicant proposed to base the safety on the comparison of AUCs (area under curve) described below. In the recent submissi","page":59,"pdf":"sccs_o_094.pdf","row_type":"noael_study","study_id":"sccs_o_094_noael_015"}

sccs_o_094.pdf

{"dose":"For the calculation of the MoS, a NOAEL of 4 mg/kg bw/d was used.","effect":"SCCS/1443/11 Opinion on p-phenylenediamine ___________________________________________________________________________________________ 59 3.3.13. Safety evaluation (including calculation of the MoS) • Evaluation based on Margin of Safety (MoS) In 2006 the SCCP concluded that, based on the classical MoS approach, the safety of p- phenylenediamine used as an oxidative hair dye at an applied concentration of 2% could not be warranted. For the calculation of the MoS, a NOAEL of 4 mg/kg bw/d was used. This NOAEL was derived from a 90 days oral toxicity study in which mean absolute and body- weight related liver and kidney weights were significantly increased for males and females, at 8 mg/kg bw/d and 16 mg/kg bw/d respectively, and minimal myodegeneration on skeletal muscle were observed in one male and one female of the high dose group. The MoS resulted in 77. The applicant proposed to base the safety on the comparison of AUCs (area under curve) described below. In the recent submissi","page":59,"pdf":"sccs_o_094.pdf","row_type":"noael_study","study_id":"sccs_o_094_noael_015"}

sccs_o_094.pdf

{"dose":"For the calculation of the MoS, a NOAEL of 4 mg/kg bw/d was used.","effect":"SCCS/1443/11 Opinion on p-phenylenediamine ___________________________________________________________________________________________ 59 3.3.13. Safety evaluation (including calculation of the MoS) • Evaluation based on Margin of Safety (MoS) In 2006 the SCCP concluded that, based on the classical MoS approach, the safety of p- phenylenediamine used as an oxidative hair dye at an applied concentration of 2% could not be warranted. For the calculation of the MoS, a NOAEL of 4 mg/kg bw/d was used. This NOAEL was derived from a 90 days oral toxicity study in which mean absolute and body- weight related liver and kidney weights were significantly increased for males and females, at 8 mg/kg bw/d and 16 mg/kg bw/d respectively, and minimal myodegeneration on skeletal muscle were observed in one male and one female of the high dose group. The MoS resulted in 77. The applicant proposed to base the safety on the comparison of AUCs (area under curve) described below. In the recent submissi","page":59,"pdf":"sccs_o_094.pdf","row_type":"noael_study","study_id":"sccs_o_094_noael_015"}

sccs_o_094.pdf

SOURCE_SUBDIR=sccs_o_094; REPORT_TITLE=OPINION ON p-Phenylenediamine COLIPA n° A7; OPINION_NUMBER=SCCS/1443/11; COMMITTEE=Scientific Committee on Consumer Safety (SCCS); REPORT_DATE=18 September 2012; VALUE_TEXT=4; DOSE=In this approach, the AUC in rats following a peroral dosage of 4 mg/kg bw (corresponding to the NOAEL) was compared to the AUC in humans following application of a hair dye containing 14C-labeled PPD.; EFFECT=SCCS-rejected applicant NOAEL: ith couplers and /or hydrogen peroxide as well in a carcinogenicity study were reported. • The generally accepted approach (MOS approach) according to the Notes of Guidance results in a MoS of 77. However, when toxicokinetic studies are considered, a minimum MoS of 25 can be set. A number of toxicokinetic studies were performed and the applicant proposed to base the safety on the comparison of AUCs (area under curve). In this approach, the AUC in rats following a peroral dosage of 4 mg/kg bw (corresponding to the NOAEL) was compared to the AUC in humans following application of a hair dye containing 14C-labeled PPD. In this case a safety margin of 16.3 was obtained which is not considered sufficient by the SCCP. • On the other hand, experimental evidence was provided that PPD is metabolised in the skin to acetylated (i.e. detoxified) derivatives and, furthermore, that presumably activation of PPD (formation of monoxygenated derivatives) does not occur. The SCCP is of the opinion that the information submitted is insufficient to; CITATION_NUMBERS=[]; DETAILS_JSON={"cas_number":"106-50-3","citation":"","dose":"In this approach, the AUC in rats following a peroral dosage of 4 mg/kg bw (corresponding to the NOAEL) was compared to the AUC in humans following application of a hair dye containing 14C-labeled PPD.","duration":"","effect":"SCCS-rejected applicant NOAEL: ith couplers and /or hydrogen peroxide as well in a carcinogenicity study were reported. • The generally accepted approach (MOS approach) according to the Notes of Guidance results in a MoS of 77. However, when toxicokinetic studies are considered, a minimum MoS of 25 can be set. A number of toxicokinetic studies were performed and the applicant proposed to base the safety on the comparison of AUCs (area under curve). In this approach, the AUC in rats following a peroral dosage of 4 mg/kg bw (corresponding to the NOAEL) was compared to the AUC in humans following application of a hair dye containing 14C-labeled PPD. In this case a safety margin of 16.3 was obtained which is not considered sufficient by the SCCP. • On the other hand, experimental evidence was provided that PPD is metabolised in the skin to acetylated (i.e. detoxified) derivatives and, furthermore, that presumably activation of PPD (formation of monoxygenated derivatives) does not occur. The SCCP is of the opinion that the information submitted is insufficient to","endpoint":"carcinogenicity","ingredient":"s from temporary tattoos and clothing textiles. PPD is an extreme","loael_value":"","noael_unit":"mg/kg bw","noael_value":"4","page":5,"route":"","species":"rat","study_id":"sccs_o_094_noael_001"}

sccs_o_094.pdf

SOURCE_SUBDIR=sccs_o_094; REPORT_TITLE=OPINION ON p-Phenylenediamine COLIPA n° A7; OPINION_NUMBER=SCCS/1443/11; COMMITTEE=Scientific Committee on Consumer Safety (SCCS); REPORT_DATE=18 September 2012; VALUE_TEXT=5; DOSE=Body weight gain was transiently slightly lower during the first 3 days of treatment at 10 and 20 mg/kg bw/day (not statistically significantly different), food consumption was not affected.; EFFECT=d effects in dams were noted with regard to clinical observations and post-mortem findings. Body weight gain was transiently slightly lower during the first 3 days of treatment at 10 and 20 mg/kg bw/day (not statistically significantly different), food consumption was not affected. Foetal body weight was lower at 20 mg/kg bw/day, but the difference was statistically not significant. At this dose also retardation in ossification was seen (supraoccipital, sternebrae, thoracic vertebrae, metacarpals). Conclusion The NOEL of maternal toxicity is 5 mg/kg bw/day whereas the NOAEL of developmental toxicity is 10 mg/kg bw/day. Ref.: 8 (suppl. data, 12/2005) 3.3.9. Toxicokinetics and metabolism Pharmacokinetics of [14C]-p-phenylenediamine in rats following oral administration and plasma metabolites after dermal administration Guideline: / Test system: Sprague-Dawley rats Treatment groups: A kinetics: 6 males and 6 females 6.45 mg/kg bw, once by gavage B excretion: 3 males and 3 females 6.45 mg/kg bw, once by gavage C metabolism: 3; CITATION=Ref.: 8 (suppl; CITATION_NUMBERS=[8]; REFERENCE=Ref.: 8 (suppl; DETAILS_JSON={"cas_number":"106-50-3","citation":"Ref.: 8 (suppl","dose":"Body weight gain was transiently slightly lower during the first 3 days of treatment at 10 and 20 mg/kg bw/day (not statistically significantly different), food consumption was not affected.","duration":"3 days","effect":"d effects in dams were noted with regard to clinical observations and post-mortem findings. Body weight gain was transiently slightly lower during the first 3 days of treatment at 10 and 20 mg/kg bw/day (not statistically significantly different), food consumption was not affected. Foetal body weight was lower at 20 mg/kg bw/day, but the difference was statistically not significant. At this dose also retardation in ossification was seen (supraoccipital, sternebrae, thoracic vertebrae, metacarpals). Conclusion The NOEL of maternal toxicity is 5 mg/kg bw/day whereas the NOAEL of developmental toxicity is 10 mg/kg bw/day. Ref.: 8 (suppl. data, 12/2005) 3.3.9. Toxicokinetics and metabolism Pharmacokinetics of [14C]-p-phenylenediamine in rats following oral administration and plasma metabolites after dermal administration Guideline: / Test system: Sprague-Dawley rats Treatment groups: A kinetics: 6 males and 6 females 6.45 mg/kg bw, once by gavage B excretion: 3 males and 3 females 6.45 mg/kg bw, once by gavage C metabolism: 3","endpoint":"developmental toxicity","ingredient":"s from temporary tattoos and clothing textiles. PPD is an extreme","loael_value":"","noael_unit":"mg/kg bw/day","noael_value":"5","page":51,"route":"oral","species":"rat","study_id":"sccs_o_094_noael_012"}

sccs_o_094.pdf

SOURCE_SUBDIR=sccs_o_094; REPORT_TITLE=OPINION ON p-Phenylenediamine COLIPA n° A7; OPINION_NUMBER=SCCS/1443/11; COMMITTEE=Scientific Committee on Consumer Safety (SCCS); REPORT_DATE=18 September 2012; VALUE_TEXT=5; DOSE=Body weight gain was transiently slightly lower during the first 3 days of treatment at 10 and 20 mg/kg bw/day (not statistically significantly different), food consumption was not affected.; EFFECT=ervations and post-mortem findings. Body weight gain was transiently slightly lower during the first 3 days of treatment at 10 and 20 mg/kg bw/day (not statistically significantly different), food consumption was not affected. Foetal body weight was lower at 20 mg/kg bw/day, but the difference was statistically not significant. At this dose also retardation in ossification was seen (supraoccipital, sternebrae, thoracic vertebrae, metacarpals). Conclusion The NOEL of maternal toxicity is 5 mg/kg bw/day whereas the NOAEL of developmental toxicity is 10 mg/kg bw/day. Ref.: 8 (suppl. data, 12/2005) 3.3.9. Toxicokinetics and metabolism Pharmacokinetics of [14C]-p-phenylenediamine in rats following oral administration and plasma metabolites after dermal administration Guideline: / Test system: Sprague-Dawley rats Treatment groups: A kinetics: 6 males and 6 females 6.45 mg/kg bw, once by gavage B excretion: 3 males and 3 females 6.45 mg/kg bw, once by gavage C metabolism: 3 males and 3 females 49.9 mg/kg bw, dermal application (so; CITATION=Ref.: 8 (suppl; CITATION_NUMBERS=[8]; REFERENCE=Ref.: 8 (suppl; DETAILS_JSON={"cas_number":"106-50-3","citation":"Ref.: 8 (suppl","dose":"Body weight gain was transiently slightly lower during the first 3 days of treatment at 10 and 20 mg/kg bw/day (not statistically significantly different), food consumption was not affected.","duration":"3 days","effect":"ervations and post-mortem findings. Body weight gain was transiently slightly lower during the first 3 days of treatment at 10 and 20 mg/kg bw/day (not statistically significantly different), food consumption was not affected. Foetal body weight was lower at 20 mg/kg bw/day, but the difference was statistically not significant. At this dose also retardation in ossification was seen (supraoccipital, sternebrae, thoracic vertebrae, metacarpals). Conclusion The NOEL of maternal toxicity is 5 mg/kg bw/day whereas the NOAEL of developmental toxicity is 10 mg/kg bw/day. Ref.: 8 (suppl. data, 12/2005) 3.3.9. Toxicokinetics and metabolism Pharmacokinetics of [14C]-p-phenylenediamine in rats following oral administration and plasma metabolites after dermal administration Guideline: / Test system: Sprague-Dawley rats Treatment groups: A kinetics: 6 males and 6 females 6.45 mg/kg bw, once by gavage B excretion: 3 males and 3 females 6.45 mg/kg bw, once by gavage C metabolism: 3 males and 3 females 49.9 mg/kg bw, dermal application (so","endpoint":"developmental toxicity","ingredient":"s from temporary tattoos and clothing textiles. PPD is an extreme","loael_value":"","noael_unit":"mg/kg bw/day","noael_value":"5","page":51,"route":"oral","species":"rat","study_id":"sccs_o_094_noael_013"}

sccs_o_094.pdf

SOURCE_SUBDIR=sccs_o_094; REPORT_TITLE=OPINION ON p-Phenylenediamine COLIPA n° A7; OPINION_NUMBER=SCCS/1443/11; COMMITTEE=Scientific Committee on Consumer Safety (SCCS); REPORT_DATE=18 September 2012; VALUE_TEXT== 0.04; DOSE=Therefore, the SCCS sets the NOAEL for subchronic toxicity at 8 mg/kg bw/d.; EFFECT=elation to PPD treatment cannot be excluded. Therefore, the SCCS sets the NOAEL for subchronic toxicity at 8 mg/kg bw/d. For the MoS calculation a skin surface area of 580 cm2 was used (see Notes of Guidance). CALCULATION OF THE MARGIN OF SAFETY p-phenylenediamine Absorption through the skin A (mean + 1SD) = 4.47 µg/cm² Skin Area surface SAS = 580 cm2 Dermal absorption per treatment SAS x A x 0.001 = 2.6 mg Typical body weight of human = 60 kg Systemic exposure dose (SED) SAS x A x 0.001/60 = 0.04 mg/kg bw/d No Observed Adverse Effect Level NOAEL = 8 mg/kg bw/d (subchronic toxicity, oral, rat) MOS = 200 • Evaluation based on toxicokinetics; CITATION_NUMBERS=[]; DETAILS_JSON={"cas_number":"106-50-3","citation":"","dose":"Therefore, the SCCS sets the NOAEL for subchronic toxicity at 8 mg/kg bw/d.","duration":"subchronic","effect":"elation to PPD treatment cannot be excluded. Therefore, the SCCS sets the NOAEL for subchronic toxicity at 8 mg/kg bw/d. For the MoS calculation a skin surface area of 580 cm2 was used (see Notes of Guidance). CALCULATION OF THE MARGIN OF SAFETY p-phenylenediamine Absorption through the skin A (mean + 1SD) = 4.47 µg/cm² Skin Area surface SAS = 580 cm2 Dermal absorption per treatment SAS x A x 0.001 = 2.6 mg Typical body weight of human = 60 kg Systemic exposure dose (SED) SAS x A x 0.001/60 = 0.04 mg/kg bw/d No Observed Adverse Effect Level NOAEL = 8 mg/kg bw/d (subchronic toxicity, oral, rat) MOS = 200 • Evaluation based on toxicokinetics","endpoint":"repeated dose toxicity","ingredient":"s from temporary tattoos and clothing textiles. PPD is an extreme","loael_value":"","noael_unit":"mg/kg bw/d","noael_value":"= 0.04","page":59,"route":"oral","species":"rat","study_id":"sccs_o_094_noael_022"}

sccs_o_094.pdf

SOURCE_SUBDIR=sccs_o_094; REPORT_TITLE=OPINION ON p-Phenylenediamine COLIPA n° A7; OPINION_NUMBER=SCCS/1443/11; COMMITTEE=Scientific Committee on Consumer Safety (SCCS); REPORT_DATE=18 September 2012; VALUE_TEXT=4.0; DOSE=Comparison of the human plasma AUC with that of rats at the NOAEL of a subchronic oral toxicity study (4.0 mg/kg bw/day) yields a toxicokinetic-based safety margin of 16.3-fold.; EFFECT=mic exposure characterised by plasma Cmax values for both sexes of approximately 3.9 µg-eq/ml (4.10 ± 0.04 and 3.73 ± 0.23 µg/ml in males and females, respectively) and a mean plasma AUC0-24h of approximately 10.8 µg-eq * hr/ml. In human volunteers (N=8), hair dyeing with a dark-shade, 2.0% [14C]-PPD-containing hair dye produced measurable plasma values with a Cmax of 0.087 µg-eq/ml and a mean AUC0-24h of 0.66 µgeq*hr/ml (mean value of individual AUCs). Comparison of the human plasma AUC with that of rats at the NOAEL of a subchronic oral toxicity study (4.0 mg/kg bw/day) yields a toxicokinetic-based safety margin of 16.3-fold. According to WHO, the 100-fold uncertainty factor can be subdivided in interspecies differences (10-fold) in toxicodynamics (2.5) and toxicokinetics (4) and inter-individual differences (10-fold) in toxicodynamics (3.2) and toxicokinetics (3.2). When AUC values are available from relevant human and animal kinetic studies, these values can be directly used for the calculation of the MoS. When these AUCs; CITATION_NUMBERS=[]; DETAILS_JSON={"cas_number":"106-50-3","citation":"","dose":"Comparison of the human plasma AUC with that of rats at the NOAEL of a subchronic oral toxicity study (4.0 mg/kg bw/day) yields a toxicokinetic-based safety margin of 16.3-fold.","duration":"subchronic","effect":"mic exposure characterised by plasma Cmax values for both sexes of approximately 3.9 µg-eq/ml (4.10 ± 0.04 and 3.73 ± 0.23 µg/ml in males and females, respectively) and a mean plasma AUC0-24h of approximately 10.8 µg-eq * hr/ml. In human volunteers (N=8), hair dyeing with a dark-shade, 2.0% [14C]-PPD-containing hair dye produced measurable plasma values with a Cmax of 0.087 µg-eq/ml and a mean AUC0-24h of 0.66 µgeq*hr/ml (mean value of individual AUCs). Comparison of the human plasma AUC with that of rats at the NOAEL of a subchronic oral toxicity study (4.0 mg/kg bw/day) yields a toxicokinetic-based safety margin of 16.3-fold. According to WHO, the 100-fold uncertainty factor can be subdivided in interspecies differences (10-fold) in toxicodynamics (2.5) and toxicokinetics (4) and inter-individual differences (10-fold) in toxicodynamics (3.2) and toxicokinetics (3.2). When AUC values are available from relevant human and animal kinetic studies, these values can be directly used for the calculation of the MoS. When these AUCs","endpoint":"repeated dose toxicity","ingredient":"s from temporary tattoos and clothing textiles. PPD is an extreme","loael_value":"","noael_unit":"mg/kg bw/day","noael_value":"4.0","page":60,"route":"oral","species":"rat","study_id":"sccs_o_094_noael_026"}

sccs_o_094.pdf

SOURCE_SUBDIR=sccs_o_094; REPORT_TITLE=OPINION ON p-Phenylenediamine COLIPA n° A7; OPINION_NUMBER=SCCS/1443/11; COMMITTEE=Scientific Committee on Consumer Safety (SCCS); REPORT_DATE=18 September 2012; VALUE_TEXT=< 5; DOSE=At 5 mg/kg bw only LDH was changed. - Mean absolute and relative liver weights raised in males given 40 mg/kg bw/day while mean relative thyroid weights raised in females given 10 mg/kg bw/day and greater. - Histopathological treatment findings were restricted to minimal myodegeneration noted in the skeletal muscle of 3 females given 40 mg/kg bw...; EFFECT=(increased alanine and/or aspartate aminotransferase, creatinine phosphokinase and lactate dehydrogenase (LDH) levels). At 5 mg/kg bw only LDH was changed. - Mean absolute and relative liver weights raised in males given 40 mg/kg bw/day while mean relative thyroid weights raised in females given 10 mg/kg bw/day and greater. - Histopathological treatment findings were restricted to minimal myodegeneration noted in the skeletal muscle of 3 females given 40 mg/kg bw/day. Under the experimental conditions adopted the NOEL was < 5 mg/kg bw/day. Ref.: 120 3.3.5.2. Sub-chronic (90 days) oral / dermal / inhalation toxicity Taken from SCCP/0989/06 Oral toxicity A 13-week study was conducted in 150 Crl:CD(SD)BR rats (5 groups, 15 animals per sex) according to the OECD 408 (1981). PPD was administered by gavage at corresponding dose levels of 2, 4, 8 and 16 mg/kg bw/day while the control group received the vehicle only (deionised boiled water). All doses were administered under a same 10 ml/kg bw volume. The animals were examined twic; CITATION=Ref.: 120 3; CITATION_NUMBERS=[120,3]; REFERENCE=Ref.: 120 3; DETAILS_JSON={"cas_number":"106-50-3","citation":"Ref.: 120 3","dose":"At 5 mg/kg bw only LDH was changed. - Mean absolute and relative liver weights raised in males given 40 mg/kg bw/day while mean relative thyroid weights raised in females given 10 mg/kg bw/day and greater. - Histopathological treatment findings were restricted to minimal myodegeneration noted in the skeletal muscle of 3 females given 40 mg/kg bw...","duration":"Sub-chronic","effect":"(increased alanine and/or aspartate aminotransferase, creatinine phosphokinase and lactate dehydrogenase (LDH) levels). At 5 mg/kg bw only LDH was changed. - Mean absolute and relative liver weights raised in males given 40 mg/kg bw/day while mean relative thyroid weights raised in females given 10 mg/kg bw/day and greater. - Histopathological treatment findings were restricted to minimal myodegeneration noted in the skeletal muscle of 3 females given 40 mg/kg bw/day. Under the experimental conditions adopted the NOEL was < 5 mg/kg bw/day. Ref.: 120 3.3.5.2. Sub-chronic (90 days) oral / dermal / inhalation toxicity Taken from SCCP/0989/06 Oral toxicity A 13-week study was conducted in 150 Crl:CD(SD)BR rats (5 groups, 15 animals per sex) according to the OECD 408 (1981). PPD was administered by gavage at corresponding dose levels of 2, 4, 8 and 16 mg/kg bw/day while the control group received the vehicle only (deionised boiled water). All doses were administered under a same 10 ml/kg bw volume. The animals were examined twic","endpoint":"repeated dose toxicity","ingredient":"s from temporary tattoos and clothing textiles. PPD is an extreme","loael_value":"","noael_unit":"mg/kg bw/day","noael_value":"< 5","page":16,"route":"oral","species":"rat","study_id":"sccs_o_094_noael_002"}

sccs_o_094.pdf

SOURCE_SUBDIR=sccs_o_094; REPORT_TITLE=OPINION ON p-Phenylenediamine COLIPA n° A7; OPINION_NUMBER=SCCS/1443/11; COMMITTEE=Scientific Committee on Consumer Safety (SCCS); REPORT_DATE=18 September 2012; VALUE_TEXT=5; DOSE=SCCS/1443/11 Opinion on p-phenylenediamine ___________________________________________________________________________________________ 63 on skeletal muscle was noted in the 90-day study on 1 male and 1 female of the high dose group (16 mg/kg bw/d).; EFFECT=SCCS/1443/11 Opinion on p-phenylenediamine ___________________________________________________________________________________________ 63 on skeletal muscle was noted in the 90-day study on 1 male and 1 female of the high dose group (16 mg/kg bw/d). Although this was also observed in the respective control group a relation to PPD treatment cannot be excluded. Therefore the SCCS sets the NOAEL for subchronic toxicity at 8 mg/kg bw/d. In a gavage developmental toxicity study in rats the NOEL of maternal toxicity is 5 mg/kg bw/day whereas the NOAEL of developmental toxicity is 10 mg/kg bw/day. Studies on reproductive toxicity were only performed with PPD in hair dye formulations. The results were not consistent. Irritation, sensitisation PPD was not irritant or corrosive for the skin and the eye when applied in a 2.5% aqueous solution. PPD was shown to be an extremely potent contact allergen in animals. p-Phenylenediamine is a frequent allergen in humans, which is of concern. It is recognized that; CITATION_NUMBERS=[]; DETAILS_JSON={"cas_number":"106-50-3","citation":"","dose":"SCCS/1443/11 Opinion on p-phenylenediamine ___________________________________________________________________________________________ 63 on skeletal muscle was noted in the 90-day study on 1 male and 1 female of the high dose group (16 mg/kg bw/d).","duration":"90-day","effect":"SCCS/1443/11 Opinion on p-phenylenediamine ___________________________________________________________________________________________ 63 on skeletal muscle was noted in the 90-day study on 1 male and 1 female of the high dose group (16 mg/kg bw/d). Although this was also observed in the respective control group a relation to PPD treatment cannot be excluded. Therefore the SCCS sets the NOAEL for subchronic toxicity at 8 mg/kg bw/d. In a gavage developmental toxicity study in rats the NOEL of maternal toxicity is 5 mg/kg bw/day whereas the NOAEL of developmental toxicity is 10 mg/kg bw/day. Studies on reproductive toxicity were only performed with PPD in hair dye formulations. The results were not consistent. Irritation, sensitisation PPD was not irritant or corrosive for the skin and the eye when applied in a 2.5% aqueous solution. PPD was shown to be an extremely potent contact allergen in animals. p-Phenylenediamine is a frequent allergen in humans, which is of concern. It is recognized that","endpoint":"repeated dose toxicity","ingredient":"s from temporary tattoos and clothing textiles. PPD is an extreme","loael_value":"","noael_unit":"mg/kg bw/day","noael_value":"5","page":63,"route":"oral","species":"rat","study_id":"sccs_o_094_noael_041"}

sccs_o_094.pdf

SOURCE_SUBDIR=sccs_o_094; REPORT_TITLE=OPINION ON p-Phenylenediamine COLIPA n° A7; OPINION_NUMBER=SCCS/1443/11; COMMITTEE=Scientific Committee on Consumer Safety (SCCS); REPORT_DATE=18 September 2012; VALUE_TEXT=5; DOSE=enylenediamine ___________________________________________________________________________________________ 63 on skeletal muscle was noted in the 90-day study on 1 male and 1 female of the high dose group (16 mg/kg bw/d).; EFFECT=enylenediamine ___________________________________________________________________________________________ 63 on skeletal muscle was noted in the 90-day study on 1 male and 1 female of the high dose group (16 mg/kg bw/d). Although this was also observed in the respective control group a relation to PPD treatment cannot be excluded. Therefore the SCCS sets the NOAEL for subchronic toxicity at 8 mg/kg bw/d. In a gavage developmental toxicity study in rats the NOEL of maternal toxicity is 5 mg/kg bw/day whereas the NOAEL of developmental toxicity is 10 mg/kg bw/day. Studies on reproductive toxicity were only performed with PPD in hair dye formulations. The results were not consistent. Irritation, sensitisation PPD was not irritant or corrosive for the skin and the eye when applied in a 2.5% aqueous solution. PPD was shown to be an extremely potent contact allergen in animals. p-Phenylenediamine is a frequent allergen in humans, which is of concern. It is recognized that allergic reactions to it may be severe; it is an extreme; CITATION_NUMBERS=[]; DETAILS_JSON={"cas_number":"106-50-3","citation":"","dose":"enylenediamine ___________________________________________________________________________________________ 63 on skeletal muscle was noted in the 90-day study on 1 male and 1 female of the high dose group (16 mg/kg bw/d).","duration":"90-day","effect":"enylenediamine ___________________________________________________________________________________________ 63 on skeletal muscle was noted in the 90-day study on 1 male and 1 female of the high dose group (16 mg/kg bw/d). Although this was also observed in the respective control group a relation to PPD treatment cannot be excluded. Therefore the SCCS sets the NOAEL for subchronic toxicity at 8 mg/kg bw/d. In a gavage developmental toxicity study in rats the NOEL of maternal toxicity is 5 mg/kg bw/day whereas the NOAEL of developmental toxicity is 10 mg/kg bw/day. Studies on reproductive toxicity were only performed with PPD in hair dye formulations. The results were not consistent. Irritation, sensitisation PPD was not irritant or corrosive for the skin and the eye when applied in a 2.5% aqueous solution. PPD was shown to be an extremely potent contact allergen in animals. p-Phenylenediamine is a frequent allergen in humans, which is of concern. It is recognized that allergic reactions to it may be severe; it is an extreme","endpoint":"repeated dose toxicity","ingredient":"s from temporary tattoos and clothing textiles. PPD is an extreme","loael_value":"","noael_unit":"mg/kg bw/day","noael_value":"5","page":63,"route":"oral","species":"rat","study_id":"sccs_o_094_noael_042"}

sccs_o_094.pdf

SOURCE_SUBDIR=sccs_o_094; REPORT_TITLE=OPINION ON p-Phenylenediamine COLIPA n° A7; OPINION_NUMBER=SCCS/1443/11; COMMITTEE=Scientific Committee on Consumer Safety (SCCS); REPORT_DATE=18 September 2012; VALUE_TEXT=5; DOSE=In a subchronic toxicity study the NOAEL was 8 mg/kg bw/d and is used as the basis for the safety evaluation.; EFFECT=drawn. However, on the basis of the toxicokinetic and mutagenicity data, it is unlikely that PPD in oxidative hair dye formulations would pose a carcinogenic risk for the consumer. Safety assessment A Conventional approach based on NOAEL: In a subchronic toxicity study the NOAEL was 8 mg/kg bw/d and is used as the basis for the safety evaluation. The highest cumulative penetration obtained in relevant studies on percutaneous absorption of PPD was 4.47 μg/cm². This leads to a margin of safety of 200. Even if the NOEL for maternal toxicity of 5 mg/kg bw/d would have been used, the resulting MoS would be sufficient (125). B Toxicokinetic based approach: In human volunteers (N=16), hair dyeing with a 2.0% [14C]-PPD-containing hair dye produced an AUC0-infinity value of 1415 PPD equivalents (ng- eq/g)*h. This human plasma AUC was compared with that of rats at the NOAEL of a subchronic oral toxicity study (8.0 mg/kg bw/day) based on data from the 6.45 mg/kg bw kinetic study. The AUC0-infinity value in rats was 33038 PPD equivalent; CITATION_NUMBERS=[]; DETAILS_JSON={"cas_number":"106-50-3","citation":"","dose":"In a subchronic toxicity study the NOAEL was 8 mg/kg bw/d and is used as the basis for the safety evaluation.","duration":"subchronic","effect":"drawn. However, on the basis of the toxicokinetic and mutagenicity data, it is unlikely that PPD in oxidative hair dye formulations would pose a carcinogenic risk for the consumer. Safety assessment A Conventional approach based on NOAEL: In a subchronic toxicity study the NOAEL was 8 mg/kg bw/d and is used as the basis for the safety evaluation. The highest cumulative penetration obtained in relevant studies on percutaneous absorption of PPD was 4.47 μg/cm². This leads to a margin of safety of 200. Even if the NOEL for maternal toxicity of 5 mg/kg bw/d would have been used, the resulting MoS would be sufficient (125). B Toxicokinetic based approach: In human volunteers (N=16), hair dyeing with a 2.0% [14C]-PPD-containing hair dye produced an AUC0-infinity value of 1415 PPD equivalents (ng- eq/g)*h. This human plasma AUC was compared with that of rats at the NOAEL of a subchronic oral toxicity study (8.0 mg/kg bw/day) based on data from the 6.45 mg/kg bw kinetic study. The AUC0-infinity value in rats was 33038 PPD equivalent","endpoint":"repeated dose toxicity","ingredient":"s from temporary tattoos and clothing textiles. PPD is an extreme","loael_value":"","noael_unit":"mg/kg bw/d","noael_value":"5","page":65,"route":"oral","species":"rat","study_id":"sccs_o_094_noael_045"}

sccs_o_094.pdf

SOURCE_SUBDIR=sccs_o_094; REPORT_TITLE=OPINION ON p-Phenylenediamine COLIPA n° A7; OPINION_NUMBER=SCCS/1443/11; COMMITTEE=Scientific Committee on Consumer Safety (SCCS); REPORT_DATE=18 September 2012; VALUE_TEXT=8; DOSE=ubstituted derivatives can induce myotoxicity (e.g. even after 3 days of administration of 36.2 mg/kg bw, see Ref.; EFFECT=ubstituted derivatives can induce myotoxicity (e.g. even after 3 days of administration of 36.2 mg/kg bw, see Ref. I). This myodegeneration in the skeletal muscle was also noted in the 28-day study in 3 females given 40 mg/kg bw/d (Ref. 120). Minimal myodegeneration on skeletal muscle was noted in the 90-day study on 1 male and 1 female of the high dose group (16 mg/kg bw/d). Although this was also observed in the respective control group a relation to PPD treatment cannot be excluded. Therefore, the SCCS sets the NOAEL for subchronic toxicity at 8 mg/kg bw/d. For the MoS calculation a skin surface area of 580 cm2 was used (see Notes of Guidance). CALCULATION OF THE MARGIN OF SAFETY p-phenylenediamine Absorption through the skin A (mean + 1SD) = 4.47 µg/cm² Skin Area surface SAS = 580 cm2 Dermal absorption per treatment SAS x A x 0.001 = 2.6 mg Typical body weight of human = 60 kg Systemic exposure dose (SED) SAS x A x 0.001/60 = 0.04 mg/kg bw/d No Observed Adverse Effect Level NOAEL = 8 mg/kg bw/d (subchronic toxicity, ora; CITATION=(Ref. 120); CITATION_NUMBERS=[120]; REFERENCE=(Ref. 120); DETAILS_JSON={"cas_number":"106-50-3","citation":"(Ref. 120)","dose":"ubstituted derivatives can induce myotoxicity (e.g. even after 3 days of administration of 36.2 mg/kg bw, see Ref.","duration":"3 days","effect":"ubstituted derivatives can induce myotoxicity (e.g. even after 3 days of administration of 36.2 mg/kg bw, see Ref. I). This myodegeneration in the skeletal muscle was also noted in the 28-day study in 3 females given 40 mg/kg bw/d (Ref. 120). Minimal myodegeneration on skeletal muscle was noted in the 90-day study on 1 male and 1 female of the high dose group (16 mg/kg bw/d). Although this was also observed in the respective control group a relation to PPD treatment cannot be excluded. Therefore, the SCCS sets the NOAEL for subchronic toxicity at 8 mg/kg bw/d. For the MoS calculation a skin surface area of 580 cm2 was used (see Notes of Guidance). CALCULATION OF THE MARGIN OF SAFETY p-phenylenediamine Absorption through the skin A (mean + 1SD) = 4.47 µg/cm² Skin Area surface SAS = 580 cm2 Dermal absorption per treatment SAS x A x 0.001 = 2.6 mg Typical body weight of human = 60 kg Systemic exposure dose (SED) SAS x A x 0.001/60 = 0.04 mg/kg bw/d No Observed Adverse Effect Level NOAEL = 8 mg/kg bw/d (subchronic toxicity, ora","endpoint":"repeated dose toxicity","ingredient":"s from temporary tattoos and clothing textiles. PPD is an extreme","loael_value":"","noael_unit":"mg/kg bw/d","noael_value":"8","page":59,"route":"dermal","species":"human","study_id":"sccs_o_094_noael_021"}

sccs_o_094.pdf

SOURCE_SUBDIR=sccs_o_094; REPORT_TITLE=OPINION ON p-Phenylenediamine COLIPA n° A7; OPINION_NUMBER=SCCS/1443/11; COMMITTEE=Scientific Committee on Consumer Safety (SCCS); REPORT_DATE=18 September 2012; VALUE_TEXT== 8; DOSE=Therefore, the SCCS sets the NOAEL for subchronic toxicity at 8 mg/kg bw/d.; EFFECT=e excluded. Therefore, the SCCS sets the NOAEL for subchronic toxicity at 8 mg/kg bw/d. For the MoS calculation a skin surface area of 580 cm2 was used (see Notes of Guidance). CALCULATION OF THE MARGIN OF SAFETY p-phenylenediamine Absorption through the skin A (mean + 1SD) = 4.47 µg/cm² Skin Area surface SAS = 580 cm2 Dermal absorption per treatment SAS x A x 0.001 = 2.6 mg Typical body weight of human = 60 kg Systemic exposure dose (SED) SAS x A x 0.001/60 = 0.04 mg/kg bw/d No Observed Adverse Effect Level NOAEL = 8 mg/kg bw/d (subchronic toxicity, oral, rat) MOS = 200 • Evaluation based on toxicokinetics; CITATION_NUMBERS=[]; DETAILS_JSON={"cas_number":"106-50-3","citation":"","dose":"Therefore, the SCCS sets the NOAEL for subchronic toxicity at 8 mg/kg bw/d.","duration":"subchronic","effect":"e excluded. Therefore, the SCCS sets the NOAEL for subchronic toxicity at 8 mg/kg bw/d. For the MoS calculation a skin surface area of 580 cm2 was used (see Notes of Guidance). CALCULATION OF THE MARGIN OF SAFETY p-phenylenediamine Absorption through the skin A (mean + 1SD) = 4.47 µg/cm² Skin Area surface SAS = 580 cm2 Dermal absorption per treatment SAS x A x 0.001 = 2.6 mg Typical body weight of human = 60 kg Systemic exposure dose (SED) SAS x A x 0.001/60 = 0.04 mg/kg bw/d No Observed Adverse Effect Level NOAEL = 8 mg/kg bw/d (subchronic toxicity, oral, rat) MOS = 200 • Evaluation based on toxicokinetics","endpoint":"repeated dose toxicity","ingredient":"s from temporary tattoos and clothing textiles. PPD is an extreme","loael_value":"","noael_unit":"mg/kg bw/d","noael_value":"= 8","page":59,"route":"oral","species":"rat","study_id":"sccs_o_094_noael_023"}

sccs_o_094.pdf

SOURCE_SUBDIR=sccs_o_094; REPORT_TITLE=OPINION ON p-Phenylenediamine COLIPA n° A7; OPINION_NUMBER=SCCS/1443/11; COMMITTEE=Scientific Committee on Consumer Safety (SCCS); REPORT_DATE=18 September 2012; VALUE_TEXT=8; DOSE=SCCS/1443/11 Opinion on p-phenylenediamine ___________________________________________________________________________________________ 62 Comment of the SCCS For the toxicokinetics-based risk assessment, the SCCS considered that the plasma AUC in humans from the new studies should be compared to the plasma AUC in rats corresponding to the NOAEL...; EFFECT=SCCS/1443/11 Opinion on p-phenylenediamine ___________________________________________________________________________________________ 62 Comment of the SCCS For the toxicokinetics-based risk assessment, the SCCS considered that the plasma AUC in humans from the new studies should be compared to the plasma AUC in rats corresponding to the NOAEL of 8 mg/kg bw/d in the subchronic toxicity study. For the assessment of a toxicokinetic based MOS, the following data were used: • NOAEL 8 mg/kg bw/d • The AUC0-infinity value in rats of 33038 PPD equivalents (ng-eq/g)*h based on data from 6.45 mg/kg bw kinetic study) • The AUC0-infinity value in humans of 1415 PPD equivalents (ng-eq/g)*h using the data for 2% PPD applied on head From these data a toxicokinetic based MOS of 23.3 is derived. As described above, the SCCS considers that for the toxicokinetics-base; CITATION_NUMBERS=[]; DETAILS_JSON={"cas_number":"106-50-3","citation":"","dose":"SCCS/1443/11 Opinion on p-phenylenediamine ___________________________________________________________________________________________ 62 Comment of the SCCS For the toxicokinetics-based risk assessment, the SCCS considered that the plasma AUC in humans from the new studies should be compared to the plasma AUC in rats corresponding to the NOAEL...","duration":"subchronic","effect":"SCCS/1443/11 Opinion on p-phenylenediamine ___________________________________________________________________________________________ 62 Comment of the SCCS For the toxicokinetics-based risk assessment, the SCCS considered that the plasma AUC in humans from the new studies should be compared to the plasma AUC in rats corresponding to the NOAEL of 8 mg/kg bw/d in the subchronic toxicity study. For the assessment of a toxicokinetic based MOS, the following data were used: • NOAEL 8 mg/kg bw/d • The AUC0-infinity value in rats of 33038 PPD equivalents (ng-eq/g)*h based on data from 6.45 mg/kg bw kinetic study) • The AUC0-infinity value in humans of 1415 PPD equivalents (ng-eq/g)*h using the data for 2% PPD applied on head From these data a toxicokinetic based MOS of 23.3 is derived. As described above, the SCCS considers that for the toxicokinetics-base","endpoint":"repeated dose toxicity","ingredient":"s from temporary tattoos and clothing textiles. PPD is an extreme","loael_value":"","noael_unit":"mg/kg bw/d","noael_value":"8","page":62,"route":"","species":"rat","study_id":"sccs_o_094_noael_035"}

sccs_o_094.pdf

SOURCE_SUBDIR=sccs_o_094; REPORT_TITLE=OPINION ON p-Phenylenediamine COLIPA n° A7; OPINION_NUMBER=SCCS/1443/11; COMMITTEE=Scientific Committee on Consumer Safety (SCCS); REPORT_DATE=18 September 2012; VALUE_TEXT=8; DOSE=SCCS/1443/11 Opinion on p-phenylenediamine ___________________________________________________________________________________________ 63 on skeletal muscle was noted in the 90-day study on 1 male and 1 female of the high dose group (16 mg/kg bw/d).; EFFECT=SCCS/1443/11 Opinion on p-phenylenediamine ___________________________________________________________________________________________ 63 on skeletal muscle was noted in the 90-day study on 1 male and 1 female of the high dose group (16 mg/kg bw/d). Although this was also observed in the respective control group a relation to PPD treatment cannot be excluded. Therefore the SCCS sets the NOAEL for subchronic toxicity at 8 mg/kg bw/d. In a gavage developmental toxicity study in rats the NOEL of maternal toxicity is 5 mg/kg bw/day whereas the NOAEL of developmental toxicity is 10 mg/kg bw/day. Studies on reproductive toxicity were only performed with PPD in hair dye formulations. The results were not consistent. Irritation, sensitisation PPD was not irritant or corrosive for the skin and the eye when applied in a 2.5% aqueous solution. PPD was shown to be an extremely potent contact allergen in animal; CITATION_NUMBERS=[]; DETAILS_JSON={"cas_number":"106-50-3","citation":"","dose":"SCCS/1443/11 Opinion on p-phenylenediamine ___________________________________________________________________________________________ 63 on skeletal muscle was noted in the 90-day study on 1 male and 1 female of the high dose group (16 mg/kg bw/d).","duration":"90-day","effect":"SCCS/1443/11 Opinion on p-phenylenediamine ___________________________________________________________________________________________ 63 on skeletal muscle was noted in the 90-day study on 1 male and 1 female of the high dose group (16 mg/kg bw/d). Although this was also observed in the respective control group a relation to PPD treatment cannot be excluded. Therefore the SCCS sets the NOAEL for subchronic toxicity at 8 mg/kg bw/d. In a gavage developmental toxicity study in rats the NOEL of maternal toxicity is 5 mg/kg bw/day whereas the NOAEL of developmental toxicity is 10 mg/kg bw/day. Studies on reproductive toxicity were only performed with PPD in hair dye formulations. The results were not consistent. Irritation, sensitisation PPD was not irritant or corrosive for the skin and the eye when applied in a 2.5% aqueous solution. PPD was shown to be an extremely potent contact allergen in animal","endpoint":"repeated dose toxicity","ingredient":"s from temporary tattoos and clothing textiles. PPD is an extreme","loael_value":"","noael_unit":"mg/kg bw/d","noael_value":"8","page":63,"route":"oral","species":"rat","study_id":"sccs_o_094_noael_040"}

sccs_o_094.pdf

SOURCE_SUBDIR=sccs_o_094; REPORT_TITLE=OPINION ON p-Phenylenediamine COLIPA n° A7; OPINION_NUMBER=SCCS/1443/11; COMMITTEE=Scientific Committee on Consumer Safety (SCCS); REPORT_DATE=18 September 2012; VALUE_TEXT=8; DOSE=In a subchronic toxicity study the NOAEL was 8 mg/kg bw/d and is used as the basis for the safety evaluation.; EFFECT=rats. The sensitivity of these studies may have been low as they did not respond to hair dye formulations containing known carcinogens. On the basis of the present data on carcinogenicity, no conclusions with regard to carcinogenicity of PPD in oxidative hair dye formulations can be drawn. However, on the basis of the toxicokinetic and mutagenicity data, it is unlikely that PPD in oxidative hair dye formulations would pose a carcinogenic risk for the consumer. Safety assessment A Conventional approach based on NOAEL: In a subchronic toxicity study the NOAEL was 8 mg/kg bw/d and is used as the basis for the safety evaluation. The highest cumulative penetration obtained in relevant studies on percutaneous absorption of PPD was 4.47 μg/cm². This leads to a margin of safety of 200. Even if the NOEL for maternal toxicity of 5 mg/kg bw/d would have been used, the resulting MoS would be sufficient (125). B Toxicokinetic based approach: In human volunteers (N=16), hair dyeing with a 2.0% [14C]-PPD-containing hair dye produced an AUC; CITATION_NUMBERS=[]; DETAILS_JSON={"cas_number":"106-50-3","citation":"","dose":"In a subchronic toxicity study the NOAEL was 8 mg/kg bw/d and is used as the basis for the safety evaluation.","duration":"subchronic","effect":"rats. The sensitivity of these studies may have been low as they did not respond to hair dye formulations containing known carcinogens. On the basis of the present data on carcinogenicity, no conclusions with regard to carcinogenicity of PPD in oxidative hair dye formulations can be drawn. However, on the basis of the toxicokinetic and mutagenicity data, it is unlikely that PPD in oxidative hair dye formulations would pose a carcinogenic risk for the consumer. Safety assessment A Conventional approach based on NOAEL: In a subchronic toxicity study the NOAEL was 8 mg/kg bw/d and is used as the basis for the safety evaluation. The highest cumulative penetration obtained in relevant studies on percutaneous absorption of PPD was 4.47 μg/cm². This leads to a margin of safety of 200. Even if the NOEL for maternal toxicity of 5 mg/kg bw/d would have been used, the resulting MoS would be sufficient (125). B Toxicokinetic based approach: In human volunteers (N=16), hair dyeing with a 2.0% [14C]-PPD-containing hair dye produced an AUC","endpoint":"repeated dose toxicity","ingredient":"s from temporary tattoos and clothing textiles. PPD is an extreme","loael_value":"","noael_unit":"mg/kg bw/d","noael_value":"8","page":65,"route":"","species":"rat","study_id":"sccs_o_094_noael_043"}

sccs_o_094.pdf

SOURCE_SUBDIR=sccs_o_094; REPORT_TITLE=OPINION ON p-Phenylenediamine COLIPA n° A7; OPINION_NUMBER=SCCS/1443/11; COMMITTEE=Scientific Committee on Consumer Safety (SCCS); REPORT_DATE=18 September 2012; VALUE_TEXT=8; DOSE=In a subchronic toxicity study the NOAEL was 8 mg/kg bw/d and is used as the basis for the safety evaluation.; EFFECT=y have been low as they did not respond to hair dye formulations containing known carcinogens. On the basis of the present data on carcinogenicity, no conclusions with regard to carcinogenicity of PPD in oxidative hair dye formulations can be drawn. However, on the basis of the toxicokinetic and mutagenicity data, it is unlikely that PPD in oxidative hair dye formulations would pose a carcinogenic risk for the consumer. Safety assessment A Conventional approach based on NOAEL: In a subchronic toxicity study the NOAEL was 8 mg/kg bw/d and is used as the basis for the safety evaluation. The highest cumulative penetration obtained in relevant studies on percutaneous absorption of PPD was 4.47 μg/cm². This leads to a margin of safety of 200. Even if the NOEL for maternal toxicity of 5 mg/kg bw/d would have been used, the resulting MoS would be sufficient (125). B Toxicokinetic based approach: In human volunteers (N=16), hair dyeing with a 2.0% [14C]-PPD-containing hair dye produced an AUC0-infinity value of 1415 PPD equivalents (; CITATION_NUMBERS=[]; DETAILS_JSON={"cas_number":"106-50-3","citation":"","dose":"In a subchronic toxicity study the NOAEL was 8 mg/kg bw/d and is used as the basis for the safety evaluation.","duration":"subchronic","effect":"y have been low as they did not respond to hair dye formulations containing known carcinogens. On the basis of the present data on carcinogenicity, no conclusions with regard to carcinogenicity of PPD in oxidative hair dye formulations can be drawn. However, on the basis of the toxicokinetic and mutagenicity data, it is unlikely that PPD in oxidative hair dye formulations would pose a carcinogenic risk for the consumer. Safety assessment A Conventional approach based on NOAEL: In a subchronic toxicity study the NOAEL was 8 mg/kg bw/d and is used as the basis for the safety evaluation. The highest cumulative penetration obtained in relevant studies on percutaneous absorption of PPD was 4.47 μg/cm². This leads to a margin of safety of 200. Even if the NOEL for maternal toxicity of 5 mg/kg bw/d would have been used, the resulting MoS would be sufficient (125). B Toxicokinetic based approach: In human volunteers (N=16), hair dyeing with a 2.0% [14C]-PPD-containing hair dye produced an AUC0-infinity value of 1415 PPD equivalents (","endpoint":"repeated dose toxicity","ingredient":"s from temporary tattoos and clothing textiles. PPD is an extreme","loael_value":"","noael_unit":"mg/kg bw/d","noael_value":"8","page":65,"route":"","species":"human","study_id":"sccs_o_094_noael_044"}

sccs_o_094.pdf

SOURCE_SUBDIR=sccs_o_094; REPORT_TITLE=OPINION ON p-Phenylenediamine COLIPA n° A7; OPINION_NUMBER=SCCS/1443/11; COMMITTEE=Scientific Committee on Consumer Safety (SCCS); REPORT_DATE=18 September 2012; VALUE_TEXT=8.0; DOSE=Even if the NOEL for maternal toxicity of 5 mg/kg bw/d would have been used, the resulting MoS would be sufficient (125).; EFFECT=highest cumulative penetration obtained in relevant studies on percutaneous absorption of PPD was 4.47 μg/cm². This leads to a margin of safety of 200. Even if the NOEL for maternal toxicity of 5 mg/kg bw/d would have been used, the resulting MoS would be sufficient (125). B Toxicokinetic based approach: In human volunteers (N=16), hair dyeing with a 2.0% [14C]-PPD-containing hair dye produced an AUC0-infinity value of 1415 PPD equivalents (ng- eq/g)*h. This human plasma AUC was compared with that of rats at the NOAEL of a subchronic oral toxicity study (8.0 mg/kg bw/day) based on data from the 6.45 mg/kg bw kinetic study. The AUC0-infinity value in rats was 33038 PPD equivalents (ng-eq/g)*h. From these data a toxicokinetic-based safety margin of 23 was calculated. The toxicokinetic based MoS is borderline. However, in view of the intermittent exposure and the fact that human exposure through hair dyeing is mainly to N,N’-diacetyl PPD mainly formed in human skin, no concern regarding systemic toxicity is raised. 4. CONCLUSI; CITATION_NUMBERS=[]; DETAILS_JSON={"cas_number":"106-50-3","citation":"","dose":"Even if the NOEL for maternal toxicity of 5 mg/kg bw/d would have been used, the resulting MoS would be sufficient (125).","duration":"subchronic","effect":"highest cumulative penetration obtained in relevant studies on percutaneous absorption of PPD was 4.47 μg/cm². This leads to a margin of safety of 200. Even if the NOEL for maternal toxicity of 5 mg/kg bw/d would have been used, the resulting MoS would be sufficient (125). B Toxicokinetic based approach: In human volunteers (N=16), hair dyeing with a 2.0% [14C]-PPD-containing hair dye produced an AUC0-infinity value of 1415 PPD equivalents (ng- eq/g)*h. This human plasma AUC was compared with that of rats at the NOAEL of a subchronic oral toxicity study (8.0 mg/kg bw/day) based on data from the 6.45 mg/kg bw kinetic study. The AUC0-infinity value in rats was 33038 PPD equivalents (ng-eq/g)*h. From these data a toxicokinetic-based safety margin of 23 was calculated. The toxicokinetic based MoS is borderline. However, in view of the intermittent exposure and the fact that human exposure through hair dyeing is mainly to N,N’-diacetyl PPD mainly formed in human skin, no concern regarding systemic toxicity is raised. 4. CONCLUSI","endpoint":"repeated dose toxicity","ingredient":"s from temporary tattoos and clothing textiles. PPD is an extreme","loael_value":"","noael_unit":"mg/kg bw/day","noael_value":"8.0","page":65,"route":"oral","species":"rat","study_id":"sccs_o_094_noael_046"}

sccs_o_094.pdf

SOURCE_SUBDIR=sccs_o_273; REPORT_TITLE=Scientific Committee on Consumer Safety; OPINION_NUMBER=SCCS/1647/22; COMMITTEE=Scientific Committee on Consumer Safety (SCCS); REPORT_DATE=adopted on 26 October 2023; VALUE_TEXT=unclear:rat and/or humans (SCCS/1443/11, SCCS/1479/12), the interspecies and/or intra-species toxicokinetic default factor can be increased/decreased (case-by-case evaluation). Regarding substance-specific information for variations in toxicodynamics, deviation from the default value is possible if sufficiently justified. For instance, in case of different susceptibility to HPT-axis disturbances in rats and humans, a change of the interspecies toxicodynamic default factor of 2.5 may be required. * including historical NOAEL values Figure 13. Further subdivision of the uncertainty/assessment factor, taking toxicokinetics and toxicodynamics into account (based on WHO, 1994). Additional considerations: - Some cosmetic substances are not used on a daily basis, although their NOAEL values have been obtained in studies after daily administration of the substances. Combining these NOAEL values with daily exposures therefore results in a clear overestimation of the risk. The comparison of a NOAEL resulting from a daily exposure study with; EFFECT=SCCS-rejected applicant NOAEL: rat and/or humans (SCCS/1443/11, SCCS/1479/12), the interspecies and/or intra-species toxicokinetic default factor can be increased/decreased (case-by-case evaluation). Regarding substance-specific information for variations in toxicodynamics, deviation from the default value is possible if sufficiently justified. For instance, in case of different susceptibility to HPT-axis disturbances in rats and humans, a change of the interspecies toxicodynamic default factor of 2.5 may be required. * including historical NOAEL values Figure 13. Further subdivision of the uncertainty/assessment factor, taking toxicokinetics and toxicodynamics into account (based on WHO, 1994). Additional considerations: - Some cosmetic substances are not used on a daily basis, although their NOAEL values have been obtained in studies after daily administration of the substances. Combining these NOAEL values with daily exposures therefore results in a clear overestimation of the risk. The comparison of a NOAEL resulting from a daily exposure study with; CITATION_NUMBERS=[]; DETAILS_JSON={"cas_number":"","citation":"","dose":"","duration":"","effect":"SCCS-rejected applicant NOAEL: rat and/or humans (SCCS/1443/11, SCCS/1479/12), the interspecies and/or intra-species toxicokinetic default factor can be increased/decreased (case-by-case evaluation). Regarding substance-specific information for variations in toxicodynamics, deviation from the default value is possible if sufficiently justified. For instance, in case of different susceptibility to HPT-axis disturbances in rats and humans, a change of the interspecies toxicodynamic default factor of 2.5 may be required. * including historical NOAEL values Figure 13. Further subdivision of the uncertainty/assessment factor, taking toxicokinetics and toxicodynamics into account (based on WHO, 1994). Additional considerations: - Some cosmetic substances are not used on a daily basis, although their NOAEL values have been obtained in studies after daily administration of the substances. Combining these NOAEL values with daily exposures therefore results in a clear overestimation of the risk. The comparison of a NOAEL resulting from a daily exposure study with","endpoint":"","ingredient":"s................................................................... 98","loael_value":"","noael_unit":"","noael_value":"unclear:rat and/or humans (SCCS/1443/11, SCCS/1479/12), the interspecies and/or intra-species toxicokinetic default factor can be increased/decreased (case-by-case evaluation). Regarding substance-specific information for variations in toxicodynamics, deviation from the default value is possible if sufficiently justified. For instance, in case of different susceptibility to HPT-axis disturbances in rats and humans, a change of the interspecies toxicodynamic default factor of 2.5 may be required. * including historical NOAEL values Figure 13. Further subdivision of the uncertainty/assessment factor, taking toxicokinetics and toxicodynamics into account (based on WHO, 1994). Additional considerations: - Some cosmetic substances are not used on a daily basis, although their NOAEL values have been obtained in studies after daily administration of the substances. Combining these NOAEL values with daily exposures therefore results in a clear overestimation of the risk. The comparison of a NOAEL resulting from a daily exposure study with","page":94,"route":"","species":"rat","study_id":"sccs_o_273_noael_017"}

sccs_o_273.pdf

SOURCE_SUBDIR=sccs_o_273_final; REPORT_TITLE=Scientific Committee on Consumer Safety; OPINION_NUMBER=SCCS/1647/22; COMMITTEE=Scientific Committee on Consumer Safety (SCCS); REPORT_DATE=adopted on 26 October 2023; VALUE_TEXT=unclear:rat and/or humans (SCCS/1443/11, SCCS/1479/12), the interspecies and/or intra-species toxicokinetic default factor can be increased/decreased (case-by-case evaluation). Regarding substance-specific information for variations in toxicodynamics, deviation from the default value is possible if sufficiently justified. For instance, in case of different susceptibility to HPT-axis disturbances in rats and humans, a change of the interspecies toxicodynamic default factor of 2.5 may be required. * including historical NOAEL values Figure 13. Further subdivision of the uncertainty/assessment factor, taking toxicokinetics and toxicodynamics into account (based on WHO, 1994). Additional considerations: - Some cosmetic substances are not used on a daily basis, although their NOAEL values have been obtained in studies after daily administration of the substances. Combining these NOAEL values with daily exposures therefore results in a clear overestimation of the risk. The comparison of a NOAEL resulting from a daily exposure study with; EFFECT=SCCS-rejected applicant NOAEL: rat and/or humans (SCCS/1443/11, SCCS/1479/12), the interspecies and/or intra-species toxicokinetic default factor can be increased/decreased (case-by-case evaluation). Regarding substance-specific information for variations in toxicodynamics, deviation from the default value is possible if sufficiently justified. For instance, in case of different susceptibility to HPT-axis disturbances in rats and humans, a change of the interspecies toxicodynamic default factor of 2.5 may be required. * including historical NOAEL values Figure 13. Further subdivision of the uncertainty/assessment factor, taking toxicokinetics and toxicodynamics into account (based on WHO, 1994). Additional considerations: - Some cosmetic substances are not used on a daily basis, although their NOAEL values have been obtained in studies after daily administration of the substances. Combining these NOAEL values with daily exposures therefore results in a clear overestimation of the risk. The comparison of a NOAEL resulting from a daily exposure study with; CITATION_NUMBERS=[]; DETAILS_JSON={"cas_number":"","citation":"","dose":"","duration":"","effect":"SCCS-rejected applicant NOAEL: rat and/or humans (SCCS/1443/11, SCCS/1479/12), the interspecies and/or intra-species toxicokinetic default factor can be increased/decreased (case-by-case evaluation). Regarding substance-specific information for variations in toxicodynamics, deviation from the default value is possible if sufficiently justified. For instance, in case of different susceptibility to HPT-axis disturbances in rats and humans, a change of the interspecies toxicodynamic default factor of 2.5 may be required. * including historical NOAEL values Figure 13. Further subdivision of the uncertainty/assessment factor, taking toxicokinetics and toxicodynamics into account (based on WHO, 1994). Additional considerations: - Some cosmetic substances are not used on a daily basis, although their NOAEL values have been obtained in studies after daily administration of the substances. Combining these NOAEL values with daily exposures therefore results in a clear overestimation of the risk. The comparison of a NOAEL resulting from a daily exposure study with","endpoint":"","ingredient":"s................................................................... 98","loael_value":"","noael_unit":"","noael_value":"unclear:rat and/or humans (SCCS/1443/11, SCCS/1479/12), the interspecies and/or intra-species toxicokinetic default factor can be increased/decreased (case-by-case evaluation). Regarding substance-specific information for variations in toxicodynamics, deviation from the default value is possible if sufficiently justified. For instance, in case of different susceptibility to HPT-axis disturbances in rats and humans, a change of the interspecies toxicodynamic default factor of 2.5 may be required. * including historical NOAEL values Figure 13. Further subdivision of the uncertainty/assessment factor, taking toxicokinetics and toxicodynamics into account (based on WHO, 1994). Additional considerations: - Some cosmetic substances are not used on a daily basis, although their NOAEL values have been obtained in studies after daily administration of the substances. Combining these NOAEL values with daily exposures therefore results in a clear overestimation of the risk. The comparison of a NOAEL resulting from a daily exposure study with","page":94,"route":"","species":"rat","study_id":"sccs_o_273_final_noael_017"}

sccs_o_273_final.pdf

{"effect":"SCCS-rejected applicant NOAEL: rat and/or humans (SCCS/1443/11, SCCS/1479/12), the interspecies and/or intra-species toxicokinetic default factor can be increased/decreased (case-by-case evaluation). Regarding substance-specific information for variations in toxicodynamics, deviation from the default value is possible if sufficiently justified. For instance, in case of different susceptibility to HPT-axis disturbances in rats and humans, a change of the interspecies toxicodynamic default factor of 2.5 may be required. * including historical NOAEL values Figure 13. Further subdivision of the uncertainty/assessment factor, taking toxicokinetics and toxicodynamics into account (based on WHO, 1994). Additional considerations: - Some cosmetic substances are not used on a daily basis, although their NOAEL values have been obtained in studies after daily administration of the substances. Combining these NOAEL values with daily exposures therefore results in a clear overestimation of the risk. The comparison of a NOAEL resulting from a daily exposure study with","page":94,"pdf":"sccs_o_273.pdf","row_type":"noael_study","study_id":"sccs_o_273_noael_017"}

sccs_o_273.pdf

{"effect":"SCCS-rejected applicant NOAEL: rat and/or humans (SCCS/1443/11, SCCS/1479/12), the interspecies and/or intra-species toxicokinetic default factor can be increased/decreased (case-by-case evaluation). Regarding substance-specific information for variations in toxicodynamics, deviation from the default value is possible if sufficiently justified. For instance, in case of different susceptibility to HPT-axis disturbances in rats and humans, a change of the interspecies toxicodynamic default factor of 2.5 may be required. * including historical NOAEL values Figure 13. Further subdivision of the uncertainty/assessment factor, taking toxicokinetics and toxicodynamics into account (based on WHO, 1994). Additional considerations: - Some cosmetic substances are not used on a daily basis, although their NOAEL values have been obtained in studies after daily administration of the substances. Combining these NOAEL values with daily exposures therefore results in a clear overestimation of the risk. The comparison of a NOAEL resulting from a daily exposure study with","page":94,"pdf":"sccs_o_273.pdf","row_type":"noael_study","study_id":"sccs_o_273_noael_017"}

sccs_o_273.pdf

{"effect":"SCCS-rejected applicant NOAEL: rat and/or humans (SCCS/1443/11, SCCS/1479/12), the interspecies and/or intra-species toxicokinetic default factor can be increased/decreased (case-by-case evaluation). Regarding substance-specific information for variations in toxicodynamics, deviation from the default value is possible if sufficiently justified. For instance, in case of different susceptibility to HPT-axis disturbances in rats and humans, a change of the interspecies toxicodynamic default factor of 2.5 may be required. * including historical NOAEL values Figure 13. Further subdivision of the uncertainty/assessment factor, taking toxicokinetics and toxicodynamics into account (based on WHO, 1994). Additional considerations: - Some cosmetic substances are not used on a daily basis, although their NOAEL values have been obtained in studies after daily administration of the substances. Combining these NOAEL values with daily exposures therefore results in a clear overestimation of the risk. The comparison of a NOAEL resulting from a daily exposure study with","page":94,"pdf":"sccs_o_273.pdf","row_type":"noael_study","study_id":"sccs_o_273_noael_017"}

sccs_o_273.pdf