NOAEL Studies Cosmetic Ingredient

P-PHENYLENEDIAMINE NOAEL Studies

CAS: 106-50-3

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

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COSMOS_DB 2 endpoints

Source	Endpoint Type	Value	Unit	Species	Route	Duration	Study Type	Reference
COSMOS_DB	LOAEL	8	mg/kg bw/day	rat	oral	90 day	Subchronic	SCCP; Paraphenylenediamine -13-week oral (gavage) toxicity study in the rat. Report n° LRL/44/94; Toxicol Laboratories Limited, Herefordshire, England
COSMOS_DB	NOAEL	4	mg/kg bw/day	rat	oral	90 day	Subchronic	SCCP; Paraphenylenediamine -13-week oral (gavage) toxicity study in the rat. Report n° LRL/44/94; Toxicol Laboratories Limited, Herefordshire, England

IARC Monographs 3 endpoints

Source	Endpoint Type	Value	Unit	Species	Route	Duration	Study Type	Reference
IARC Monographs	IARC carcinogenicity classification	3	IARC group	-	-	1987	IARC Monographs	{"additional_info":"volume_publication_year=1987","evaluation_year":1987,"source_table":"iarc_classifications","volume":"16, Sup 7"}
IARC Monographs	IARC carcinogenicity classification	3	IARC group	-	-	1987	IARC Monographs	{"additional_info":"volume_publication_year=1987","evaluation_year":1987,"source_table":"iarc_classifications","volume":"16, Sup 7"}
IARC Monographs	IARC carcinogenicity classification	3	IARC group	-	-	1987	IARC Monographs	{"additional_info":"volume_publication_year=1987","evaluation_year":1987,"source_table":"iarc_classifications","volume":"16, Sup 7"}

NTP_ICE_acute_inhalation 1 endpoint

Source	Endpoint Type	Value	Unit	Species	Route	Duration	Study Type	Reference
NTP_ICE_acute_inhalation	LC50	0.92	mg/L	-	Inhalation	Duration=4 hr	In Vivo; AcuteInhalNICEATM; Rat Acute Inhalation Toxicity	sheet=Data; excel_row=5025; Record_ID=acute_inhalation_1092; Data_Type=In Vivo; Internal_Data_Source=AcuteInhalNICEATM; Mixture=Chemical; DTXSID=DTXSID9021138; Assay=Rat Acute Inhalation Toxicity; Endpoint=LC50; Response=0.92; Response_Unit=mg/L; Reference=ChemIDplus; URL_CompTox=https://comptox.epa.gov/dashboard/chemical/details/DTXSID9021138

NTP_ICE_cancer 1 endpoint

Source	Endpoint Type	Value	Unit	Species	Route	Duration	Study Type	Reference
NTP_ICE_cancer	IARC group	3	unitless	-	-	-	WOE; IARC Carcinogenicity	sheet=Data; excel_row=9844; Record_ID=cancer_2745; Data_Type=WOE; Formulation_Name=1,4-Benzenediamine; Mixture=Chemical; DTXSID=DTXSID9021138; Assay=IARC Carcinogenicity; Endpoint=IARC group; Response=3; Response_Unit=Unitless; URL=http://publications.iarc.fr/34; http://publications.iarc.fr/139; URL_CompTox=https://comptox.epa.gov/dashboard/chemical/details/DTXSID9021138

NTP_ICE_endocrine 5 endpoints

Source	Endpoint Type	Value	Unit	Species	Route	Duration	Study Type	Reference
NTP_ICE_endocrine	AC50	11.975099352854	uM	-	-	-	ERPathway2016; ER Pathway Model, Antagonist	sheet=Integrated_approaches; excel_row=782; RecordID=ERPathway2016_338; DatasetName=ERPathway2016; DTXSID=DTXSID9021138; Assay=ER Pathway Model, Antagonist; Endpoint=AC50; Response=11.975099352854; Response_Unit=uM; URL_CompTox=https://comptox.epa.gov/dashboard/chemical/details/DTXSID9021138
NTP_ICE_endocrine	ACC	9.1374189282653	uM	-	-	-	ERPathway2016; ER Pathway Model, Antagonist	sheet=Integrated_approaches; excel_row=783; RecordID=ERPathway2016_338; DatasetName=ERPathway2016; DTXSID=DTXSID9021138; Assay=ER Pathway Model, Antagonist; Endpoint=ACC; Response=9.1374189282653; Response_Unit=uM; URL_CompTox=https://comptox.epa.gov/dashboard/chemical/details/DTXSID9021138
NTP_ICE_endocrine	Model Score	0	unitless	-	-	-	ARPathway2016; AR Pathway Model, Antagonist	sheet=Integrated_approaches; excel_row=778; RecordID=ARPathway2016_478; DatasetName=ARPathway2016; DTXSID=DTXSID9021138; Assay=AR Pathway Model, Antagonist; Endpoint=Model Score; Response=0; Response_Unit=Unitless; URL_CompTox=https://comptox.epa.gov/dashboard/chemical/details/DTXSID9021138
NTP_ICE_endocrine	Model Score	0.0201	unitless	-	-	-	ERPathway2016; ER Pathway Model, Agonist	sheet=Integrated_approaches; excel_row=784; RecordID=ERPathway2016_338; DatasetName=ERPathway2016; DTXSID=DTXSID9021138; Assay=ER Pathway Model, Agonist; Endpoint=Model Score; Response=0.0201; Response_Unit=Unitless; URL_CompTox=https://comptox.epa.gov/dashboard/chemical/details/DTXSID9021138
NTP_ICE_endocrine	Model Score	0.0158	unitless	-	-	-	ERPathway2016; ER Pathway Model, Antagonist	sheet=Integrated_approaches; excel_row=785; RecordID=ERPathway2016_338; DatasetName=ERPathway2016; DTXSID=DTXSID9021138; Assay=ER Pathway Model, Antagonist; Endpoint=Model Score; Response=0.0158; Response_Unit=Unitless; URL_CompTox=https://comptox.epa.gov/dashboard/chemical/details/DTXSID9021138

NTP_ICE_skin_sensitization 219 endpoints

Source	Endpoint Type	Value	Unit	Species	Route	Duration	Study Type	Reference
NTP_ICE_skin_sensitization	CD54, EC200	30.2	ug/mL	-	Dermal	-	In Vitro; hCLAT2015; h-CLAT	sheet=Data_invitro; excel_row=3709; Record_ID=skin_sensitization_invitro_846; Data_Type=In Vitro; Internal_Data_Source=hCLAT2015; Mixture=Chemical; DTXSID=DTXSID9021138; Assay=h-CLAT; Endpoint=CD54, EC200; Reported_Response=30.2; Reported_Response_Unit=ug/mL; Response=30.2; Response_Unit=ug/mL; Reference=Sakaguchi et al. 2010; 20510347; 10.1016/j.tiv.2010.05.012\|h-CLAT RingTrial EC values for NICEATM (undated); URL_CompTox=https://comptox.epa.gov/dashboard/chemical/details/DTXSID9021138
NTP_ICE_skin_sensitization	CD54, EC200	46.8	ug/mL	-	Dermal	-	In Vitro; hCLAT2015; h-CLAT	sheet=Data_invitro; excel_row=3730; Record_ID=skin_sensitization_invitro_850; Data_Type=In Vitro; Internal_Data_Source=hCLAT2015; Mixture=Chemical; DTXSID=DTXSID9021138; Assay=h-CLAT; Endpoint=CD54, EC200; Reported_Response=46.8; Reported_Response_Unit=ug/mL; Response=46.8; Response_Unit=ug/mL; Reference=Sakaguchi et al. 2010; 20510347; 10.1016/j.tiv.2010.05.012\|h-CLAT RingTrial EC values for NICEATM (undated); URL_CompTox=https://comptox.epa.gov/dashboard/chemical/details/DTXSID9021138
NTP_ICE_skin_sensitization	CD86, EC120	0.573	ug/mL	-	Dermal	-	In Vitro; Urbisch_SkinSensitization2020; mMUSST	sheet=Data_invitro; excel_row=7796; Record_ID=skin_sensitization_invitro_1894; Data_Type=In Vitro; Internal_Data_Source=Urbisch_SkinSensitization2020; Mixture=Chemical; DTXSID=DTXSID9021138; Assay=mMUSST; Endpoint=CD86, EC120; Reported_Response=5.3; Reported_Response_Unit=uM; Conversion_Factor_Value=108.144; Conversion_Factor_Source=EPA Dashboard; Converted_Response=0.573; Converted_Response_Unit=ug/mL; Response=0.573; Response_Unit=ug/mL; Reference=Urbisch et al. 2015; 25541156; 10.1016/j.yrtph.2014.12.008; URL_CompTox=https://comptox.epa.gov/dashboard/chemical/details/DTXSID9021138
NTP_ICE_skin_sensitization	CD86, EC150	2.09	ug/mL	-	Dermal	-	In Vitro; CE_hCLAT2018; h-CLAT	sheet=Data_invitro; excel_row=2001; Record_ID=skin_sensitization_invitro_503; Data_Type=In Vitro; Internal_Data_Source=CE_hCLAT2018; Mixture=Chemical; DTXSID=DTXSID9021138; Assay=h-CLAT; Endpoint=CD86, EC150; Reported_Response=2.09; Reported_Response_Unit=ug/mL; Response=2.09; Response_Unit=ug/mL; Reference=Urbisch et al. 2015; 25541156; 10.1016/j.yrtph.2014.12.008; URL_CompTox=https://comptox.epa.gov/dashboard/chemical/details/DTXSID9021138
NTP_ICE_skin_sensitization	CD86, EC150	2	ug/mL	-	Dermal	-	In Vitro; hCLAT2015; h-CLAT	sheet=Data_invitro; excel_row=3681; Record_ID=skin_sensitization_invitro_841; Data_Type=In Vitro; Internal_Data_Source=hCLAT2015; Mixture=Chemical; DTXSID=DTXSID9021138; Assay=h-CLAT; Endpoint=CD86, EC150; Reported_Response=2; Reported_Response_Unit=ug/mL; Response=2; Response_Unit=ug/mL; Reference=Bauch et al. 2011; 21669280; 10.1016/j.tiv.2011.05.030\|Bauch et al. 2012; 22659254; 10.1016/j.yrtph.2012.05.013; URL_CompTox=https://comptox.epa.gov/dashboard/chemical/details/DTXSID9021138
NTP_ICE_skin_sensitization	CD86, EC150	<9	ug/mL	-	Dermal	-	In Vitro; hCLAT2015; h-CLAT	sheet=Data_invitro; excel_row=3711; Record_ID=skin_sensitization_invitro_846; Data_Type=In Vitro; Internal_Data_Source=hCLAT2015; Mixture=Chemical; DTXSID=DTXSID9021138; Assay=h-CLAT; Endpoint=CD86, EC150; Response_Modifier=<; Reported_Response_Modifier=<; Reported_Response=9; Reported_Response_Unit=ug/mL; Response=9; Response_Unit=ug/mL; Reference=Sakaguchi et al. 2010; 20510347; 10.1016/j.tiv.2010.05.012\|h-CLAT RingTrial EC values for NICEATM (undated); URL_CompTox=https://comptox.epa.gov/dashboard/chemical/details/DTXSID9021138
NTP_ICE_skin_sensitization	CD86, EC150	7.2	ug/mL	-	Dermal	-	In Vitro; hCLAT2015; h-CLAT	sheet=Data_invitro; excel_row=3718; Record_ID=skin_sensitization_invitro_848; Data_Type=In Vitro; Internal_Data_Source=hCLAT2015; Mixture=Chemical; DTXSID=DTXSID9021138; Assay=h-CLAT; Endpoint=CD86, EC150; Reported_Response=7.2; Reported_Response_Unit=ug/mL; Response=7.2; Response_Unit=ug/mL; Reference=Sakaguchi et al. 2010; 20510347; 10.1016/j.tiv.2010.05.012\|h-CLAT RingTrial EC values for NICEATM (undated); URL_CompTox=https://comptox.epa.gov/dashboard/chemical/details/DTXSID9021138
NTP_ICE_skin_sensitization	CD86, EC150	21.1	ug/mL	-	Dermal	-	In Vitro; hCLAT2015; h-CLAT	sheet=Data_invitro; excel_row=3728; Record_ID=skin_sensitization_invitro_850; Data_Type=In Vitro; Internal_Data_Source=hCLAT2015; Mixture=Chemical; DTXSID=DTXSID9021138; Assay=h-CLAT; Endpoint=CD86, EC150; Reported_Response=21.1; Reported_Response_Unit=ug/mL; Response=21.1; Response_Unit=ug/mL; Reference=Sakaguchi et al. 2010; 20510347; 10.1016/j.tiv.2010.05.012\|h-CLAT RingTrial EC values for NICEATM (undated); URL_CompTox=https://comptox.epa.gov/dashboard/chemical/details/DTXSID9021138
NTP_ICE_skin_sensitization	CD86, EC150	1.4	ug/mL	-	Dermal	-	In Vitro; hCLAT2015; h-CLAT	sheet=Data_invitro; excel_row=3741; Record_ID=skin_sensitization_invitro_853; Data_Type=In Vitro; Internal_Data_Source=hCLAT2015; Mixture=Chemical; DTXSID=DTXSID9021138; Assay=h-CLAT; Endpoint=CD86, EC150; Reported_Response=1.4; Reported_Response_Unit=ug/mL; Response=1.4; Response_Unit=ug/mL; Reference=Sakaguchi et al. 2010; 20510347; 10.1016/j.tiv.2010.05.012\|h-CLAT RingTrial EC values for NICEATM (undated); URL_CompTox=https://comptox.epa.gov/dashboard/chemical/details/DTXSID9021138
NTP_ICE_skin_sensitization	CD86, EC150	3.1	ug/mL	-	Dermal	-	In Vitro; Urbisch_SkinSensitization2020; U-SENS	sheet=Data_invitro; excel_row=8338; Record_ID=skin_sensitization_invitro_2312; Data_Type=In Vitro; Internal_Data_Source=Urbisch_SkinSensitization2020; Mixture=Chemical; DTXSID=DTXSID9021138; Assay=U-SENS; Endpoint=CD86, EC150; Reported_Response=28.66654337; Reported_Response_Unit=uM; Conversion_Factor_Value=108.144; Conversion_Factor_Source=EPA Dashboard; Converted_Response=3.1; Converted_Response_Unit=ug/mL; Response=3.1; Response_Unit=ug/mL; Reference=Urbisch et al. 2015; 25541156; 10.1016/j.yrtph.2014.12.008; URL_CompTox=https://comptox.epa.gov/dashboard/chemical/details/DTXSID9021138
NTP_ICE_skin_sensitization	CD86, EC150	2.36	ug/mL	-	Dermal	-	In Vitro; CE_USENSE2018; U-SENS	sheet=Data_invitro; excel_row=8492; Record_ID=skin_sensitization_invitro_2340; Data_Type=In Vitro; Internal_Data_Source=CE_USENSE2018; Mixture=Chemical; DTXSID=DTXSID9021138; Assay=U-SENS; Endpoint=CD86, EC150; Reported_Response=2.36; Reported_Response_Unit=ug/mL; Response=2.36; Response_Unit=ug/mL; Reference=Piroird et al. 2015; 25820135; 10.1016/j.tiv.2015.03.009; URL_CompTox=https://comptox.epa.gov/dashboard/chemical/details/DTXSID9021138
NTP_ICE_skin_sensitization	CV70	20.83	ug/mL	-	Dermal	-	In Vitro; CE_USENSE2018; U-SENS	sheet=Data_invitro; excel_row=8494; Record_ID=skin_sensitization_invitro_2340; Data_Type=In Vitro; Internal_Data_Source=CE_USENSE2018; Mixture=Chemical; DTXSID=DTXSID9021138; Assay=U-SENS; Endpoint=CV70; Reported_Response=20.83; Reported_Response_Unit=ug/mL; Response=20.83; Response_Unit=ug/mL; Reference=Piroird et al. 2015; 25820135; 10.1016/j.tiv.2015.03.009; URL_CompTox=https://comptox.epa.gov/dashboard/chemical/details/DTXSID9021138
NTP_ICE_skin_sensitization	CV75	36.7	ug/mL	-	Dermal	-	In Vitro; CE_hCLAT2018; h-CLAT	sheet=Data_invitro; excel_row=2003; Record_ID=skin_sensitization_invitro_503; Data_Type=In Vitro; Internal_Data_Source=CE_hCLAT2018; Mixture=Chemical; DTXSID=DTXSID9021138; Assay=h-CLAT; Endpoint=CV75; Reported_Response=36.700000000000003; Reported_Response_Unit=ug/mL; Response=36.7; Response_Unit=ug/mL; Reference=Urbisch et al. 2015; 25541156; 10.1016/j.yrtph.2014.12.008; URL_CompTox=https://comptox.epa.gov/dashboard/chemical/details/DTXSID9021138
NTP_ICE_skin_sensitization	CV75	1.6	ug/mL	-	Dermal	-	In Vitro; hCLAT2015; h-CLAT	sheet=Data_invitro; excel_row=3679; Record_ID=skin_sensitization_invitro_841; Data_Type=In Vitro; Internal_Data_Source=hCLAT2015; Mixture=Chemical; DTXSID=DTXSID9021138; Assay=h-CLAT; Endpoint=CV75; Reported_Response=1.6; Reported_Response_Unit=ug/mL; Response=1.6; Response_Unit=ug/mL; Reference=Bauch et al. 2011; 21669280; 10.1016/j.tiv.2011.05.030\|Bauch et al. 2012; 22659254; 10.1016/j.yrtph.2012.05.013; URL_CompTox=https://comptox.epa.gov/dashboard/chemical/details/DTXSID9021138
NTP_ICE_skin_sensitization	CV75	27	ug/mL	-	Dermal	-	In Vitro; hCLAT2015; h-CLAT	sheet=Data_invitro; excel_row=3708; Record_ID=skin_sensitization_invitro_846; Data_Type=In Vitro; Internal_Data_Source=hCLAT2015; Mixture=Chemical; DTXSID=DTXSID9021138; Assay=h-CLAT; Endpoint=CV75; Reported_Response=27; Reported_Response_Unit=ug/mL; Response=27; Response_Unit=ug/mL; Reference=Sakaguchi et al. 2010; 20510347; 10.1016/j.tiv.2010.05.012\|h-CLAT RingTrial EC values for NICEATM (undated); URL_CompTox=https://comptox.epa.gov/dashboard/chemical/details/DTXSID9021138
NTP_ICE_skin_sensitization	CV75	20.8	ug/mL	-	Dermal	-	In Vitro; hCLAT2015; h-CLAT	sheet=Data_invitro; excel_row=3720; Record_ID=skin_sensitization_invitro_848; Data_Type=In Vitro; Internal_Data_Source=hCLAT2015; Mixture=Chemical; DTXSID=DTXSID9021138; Assay=h-CLAT; Endpoint=CV75; Reported_Response=20.8; Reported_Response_Unit=ug/mL; Response=20.8; Response_Unit=ug/mL; Reference=Sakaguchi et al. 2010; 20510347; 10.1016/j.tiv.2010.05.012\|h-CLAT RingTrial EC values for NICEATM (undated); URL_CompTox=https://comptox.epa.gov/dashboard/chemical/details/DTXSID9021138
NTP_ICE_skin_sensitization	CV75	48.3	ug/mL	-	Dermal	-	In Vitro; hCLAT2015; h-CLAT	sheet=Data_invitro; excel_row=3732; Record_ID=skin_sensitization_invitro_850; Data_Type=In Vitro; Internal_Data_Source=hCLAT2015; Mixture=Chemical; DTXSID=DTXSID9021138; Assay=h-CLAT; Endpoint=CV75; Reported_Response=48.3; Reported_Response_Unit=ug/mL; Response=48.3; Response_Unit=ug/mL; Reference=Sakaguchi et al. 2010; 20510347; 10.1016/j.tiv.2010.05.012\|h-CLAT RingTrial EC values for NICEATM (undated); URL_CompTox=https://comptox.epa.gov/dashboard/chemical/details/DTXSID9021138
NTP_ICE_skin_sensitization	CV75	50.3	ug/mL	-	Dermal	-	In Vitro; hCLAT2015; h-CLAT	sheet=Data_invitro; excel_row=3743; Record_ID=skin_sensitization_invitro_853; Data_Type=In Vitro; Internal_Data_Source=hCLAT2015; Mixture=Chemical; DTXSID=DTXSID9021138; Assay=h-CLAT; Endpoint=CV75; Reported_Response=50.3; Reported_Response_Unit=ug/mL; Response=50.3; Response_Unit=ug/mL; Reference=Sakaguchi et al. 2010; 20510347; 10.1016/j.tiv.2010.05.012\|h-CLAT RingTrial EC values for NICEATM (undated); URL_CompTox=https://comptox.epa.gov/dashboard/chemical/details/DTXSID9021138
NTP_ICE_skin_sensitization	Concentration, 5% incidence of positive responses	0.03429	%	Human	Dermal	-	In Vivo; HPPT2020WIP; Human Maximization Test	sheet=Data_invivo; excel_row=3061; Record_ID=skin_sensitization_invivo_801; Data_Type=In Vivo; Internal_Data_Source=HPPT2020WIP; Concentration=0.2; Concentration_Units=%; Mixture=Chemical; DTXSID=DTXSID9021138; Assay=Human Maximization Test; Endpoint=Concentration, 5% incidence of positive responses; Response=0.03429; Response_Unit=%; Species=Human; Route=Dermal; Reference=Kligman 1966; 5924293; 10.1038/jid.1966.159; URL_CompTox=https://comptox.epa.gov/dashboard/chemical/details/DTXSID9021138
NTP_ICE_skin_sensitization	Concentration, 5% incidence of positive responses	0.03	%	Human	Dermal	-	In Vivo; HPPT2020WIP; Human Maximization Test	sheet=Data_invivo; excel_row=3075; Record_ID=skin_sensitization_invivo_803; Data_Type=In Vivo; Internal_Data_Source=HPPT2020WIP; Concentration=0.2; Concentration_Units=%; Mixture=Chemical; DTXSID=DTXSID9021138; Assay=Human Maximization Test; Endpoint=Concentration, 5% incidence of positive responses; Response=0.03; Response_Unit=%; Species=Human; Route=Dermal; Reference=Kligman 1966; 5924293; 10.1038/jid.1966.159; URL_CompTox=https://comptox.epa.gov/dashboard/chemical/details/DTXSID9021138
NTP_ICE_skin_sensitization	Concentration, 5% incidence of positive responses	0.023	%	Human	Dermal	-	In Vivo; HPPT2020WIP; Human Maximization Test	sheet=Data_invivo; excel_row=3089; Record_ID=skin_sensitization_invivo_805; Data_Type=In Vivo; Internal_Data_Source=HPPT2020WIP; Concentration=0.2; Concentration_Units=%; Mixture=Chemical; DTXSID=DTXSID9021138; Assay=Human Maximization Test; Endpoint=Concentration, 5% incidence of positive responses; Response=2.3E-2; Response_Unit=%; Species=Human; Route=Dermal; Reference=Kligman 1966; 5924293; 10.1038/jid.1966.159; URL_CompTox=https://comptox.epa.gov/dashboard/chemical/details/DTXSID9021138
NTP_ICE_skin_sensitization	Concentration, 5% incidence of positive responses	0.024	%	Human	Dermal	-	In Vivo; HPPT2020WIP; Human Maximization Test	sheet=Data_invivo; excel_row=3090; Record_ID=skin_sensitization_invivo_799; Data_Type=In Vivo; Internal_Data_Source=HPPT2020WIP; Concentration=0.1; Concentration_Units=%; Mixture=Chemical; DTXSID=DTXSID9021138; Assay=Human Maximization Test; Endpoint=Concentration, 5% incidence of positive responses; Response=0.024; Response_Unit=%; Species=Human; Route=Dermal; Reference=Kligman 1966; 5924293; 10.1038/jid.1966.159\|Akkan et al. 2003; Not available; Not available\|Schneider and Akkan 2004; 15135206; 10.1016/j.yrtph.2004.02.002; URL_CompTox=https://comptox.epa.gov/dashboard/chemical/details/DTXSID9021138
NTP_ICE_skin_sensitization	Concentration, 5% incidence of positive responses	0.07353	%	Human	Dermal	-	In Vivo; HPPT2020WIP; Human Maximization Test	sheet=Data_invivo; excel_row=3100; Record_ID=skin_sensitization_invivo_806; Data_Type=In Vivo; Internal_Data_Source=HPPT2020WIP; Concentration=1.0; Concentration_Units=%; Mixture=Chemical; DTXSID=DTXSID9021138; Assay=Human Maximization Test; Endpoint=Concentration, 5% incidence of positive responses; Response=0.07353; Response_Unit=%; Species=Human; Route=Dermal; Reference=Kligman 1966; 5924293; 10.1038/jid.1966.159; URL_CompTox=https://comptox.epa.gov/dashboard/chemical/details/DTXSID9021138
NTP_ICE_skin_sensitization	Concentration, 5% incidence of positive responses	0.2604	%	Human	Dermal	-	In Vivo; HPPT2020WIP; Human Maximization Test	sheet=Data_invivo; excel_row=3102; Record_ID=skin_sensitization_invivo_807; Data_Type=In Vivo; Internal_Data_Source=HPPT2020WIP; Concentration=5.0; Concentration_Units=%; Mixture=Chemical; DTXSID=DTXSID9021138; Assay=Human Maximization Test; Endpoint=Concentration, 5% incidence of positive responses; Response=0.2604; Response_Unit=%; Species=Human; Route=Dermal; Reference=Kligman 1966; 5924293; 10.1038/jid.1966.159; URL_CompTox=https://comptox.epa.gov/dashboard/chemical/details/DTXSID9021138
NTP_ICE_skin_sensitization	Concentration, 5% incidence of positive responses	0.2727	%	Human	Dermal	-	In Vivo; HPPT2020WIP; Human Maximization Test	sheet=Data_invivo; excel_row=3115; Record_ID=skin_sensitization_invivo_808; Data_Type=In Vivo; Internal_Data_Source=HPPT2020WIP; Concentration=5.0; Concentration_Units=%; Mixture=Chemical; DTXSID=DTXSID9021138; Assay=Human Maximization Test; Endpoint=Concentration, 5% incidence of positive responses; Response=0.2727; Response_Unit=%; Species=Human; Route=Dermal; Reference=Kligman 1966; 5924293; 10.1038/jid.1966.159; URL_CompTox=https://comptox.epa.gov/dashboard/chemical/details/DTXSID9021138
NTP_ICE_skin_sensitization	Concentration, 5% incidence of positive responses	0.5	%	Human	Dermal	-	In Vivo; HPPT2020WIP; Human Maximization Test	sheet=Data_invivo; excel_row=3119; Record_ID=skin_sensitization_invivo_809; Data_Type=In Vivo; Internal_Data_Source=HPPT2020WIP; Concentration=10.0; Concentration_Units=%; Mixture=Chemical; DTXSID=DTXSID9021138; Assay=Human Maximization Test; Endpoint=Concentration, 5% incidence of positive responses; Response=0.5; Response_Unit=%; Species=Human; Route=Dermal; Reference=Kligman 1966; 5924293; 10.1038/jid.1966.159; URL_CompTox=https://comptox.epa.gov/dashboard/chemical/details/DTXSID9021138
NTP_ICE_skin_sensitization	Concentration, 5% incidence of positive responses	0.006929	%	Human	Dermal	-	In Vivo; HPPT2020WIP; Human Repeat Insult Patch Test	sheet=Data_invivo; excel_row=3129; Record_ID=skin_sensitization_invivo_811; Data_Type=In Vivo; Internal_Data_Source=HPPT2020WIP; Concentration=0.01; Concentration_Units=%; Mixture=Chemical; DTXSID=DTXSID9021138; Assay=Human Repeat Insult Patch Test; Endpoint=Concentration, 5% incidence of positive responses; Response=0.006929; Response_Unit=%; Species=Human; Route=Dermal; Reference=Marzulli and Maibach 1974; 4459237; 10.1016/0015-6264(74)90367-8\|Gerberick et al. 2001; 11526521; 10.1053/ajcd.2001.23926\|Akkan et al. 2003; Not available; Not available\|Griem et al. 2003; 14623479; 10.1016/j.yrtph.2003.07.001\|Schneider and Akkan 2004; 15135206; 10.1016/j.yrtph.2004.02.002\|Basketter et al. 2005; 16283904; 10.1111/j.0105-1873.2005.00707.x\|ICCVAM 2009; Not available; https://ntp.niehs.nih.gov/iccvam/docs/immunotox_docs/llna-ps/llnaperfstds.pdf; URL_CompTox=https://comptox.epa.gov/dashboard/chemical/details/DTXSID9021138
NTP_ICE_skin_sensitization	Concentration, 5% incidence of positive responses	0.04455	%	Human	Dermal	-	In Vivo; HPPT2020WIP; Human Repeat Insult Patch Test	sheet=Data_invivo; excel_row=3144; Record_ID=skin_sensitization_invivo_812; Data_Type=In Vivo; Internal_Data_Source=HPPT2020WIP; Concentration=0.1; Concentration_Units=%; Mixture=Chemical; DTXSID=DTXSID9021138; Assay=Human Repeat Insult Patch Test; Endpoint=Concentration, 5% incidence of positive responses; Response=0.04455; Response_Unit=%; Species=Human; Route=Dermal; Reference=Marzulli and Maibach 1974; 4459237; 10.1016/0015-6264(74)90367-8\|Gerberick et al. 2001; 11526521; 10.1053/ajcd.2001.23926\|Akkan et al. 2003; Not available; Not available\|Griem et al. 2003; 14623479; 10.1016/j.yrtph.2003.07.001\|Schneider and Akkan 2004; 15135206; 10.1016/j.yrtph.2004.02.002\|Basketter et al. 2005; 16283904; 10.1111/j.0105-1873.2005.00707.x\|ICCVAM 2009; Not available; https://ntp.niehs.nih.gov/iccvam/docs/immunotox_docs/llna-ps/llnaperfstds.pdf; URL_CompTox=https://comptox.epa.gov/dashboard/chemical/details/DTXSID9021138
NTP_ICE_skin_sensitization	Concentration, 5% incidence of positive responses	0.09362	%	Human	Dermal	-	In Vivo; HPPT2020WIP; Human Repeat Insult Patch Test	sheet=Data_invivo; excel_row=3160; Record_ID=skin_sensitization_invivo_814; Data_Type=In Vivo; Internal_Data_Source=HPPT2020WIP; Concentration=1.0; Concentration_Units=%; Mixture=Chemical; DTXSID=DTXSID9021138; Assay=Human Repeat Insult Patch Test; Endpoint=Concentration, 5% incidence of positive responses; Response=0.09362; Response_Unit=%; Species=Human; Route=Dermal; Reference=Marzulli and Maibach 1974; 4459237; 10.1016/0015-6264(74)90367-8\|Gerberick et al. 2001; 11526521; 10.1053/ajcd.2001.23926\|Akkan et al. 2003; Not available; Not available\|Griem et al. 2003; 14623479; 10.1016/j.yrtph.2003.07.001\|Schneider and Akkan 2004; 15135206; 10.1016/j.yrtph.2004.02.002\|Basketter et al. 2005; 16283904; 10.1111/j.0105-1873.2005.00707.x\|ICCVAM 2009; Not available; https://ntp.niehs.nih.gov/iccvam/docs/immunotox_docs/llna-ps/llnaperfstds.pdf; URL_CompTox=https://comptox.epa.gov/dashboard/chemical/details/DTXSID9021138
NTP_ICE_skin_sensitization	Concentration, one positive response	0.02857	%	Human	Dermal	-	In Vivo; HPPT2020WIP; Human Maximization Test	sheet=Data_invivo; excel_row=3058; Record_ID=skin_sensitization_invivo_801; Data_Type=In Vivo; Internal_Data_Source=HPPT2020WIP; Concentration=0.2; Concentration_Units=%; Mixture=Chemical; DTXSID=DTXSID9021138; Assay=Human Maximization Test; Endpoint=Concentration, one positive response; Response=0.02857; Response_Unit=%; Species=Human; Route=Dermal; Reference=Kligman 1966; 5924293; 10.1038/jid.1966.159; URL_CompTox=https://comptox.epa.gov/dashboard/chemical/details/DTXSID9021138
NTP_ICE_skin_sensitization	Concentration, one positive response	0.025	%	Human	Dermal	-	In Vivo; HPPT2020WIP; Human Maximization Test	sheet=Data_invivo; excel_row=3071; Record_ID=skin_sensitization_invivo_803; Data_Type=In Vivo; Internal_Data_Source=HPPT2020WIP; Concentration=0.2; Concentration_Units=%; Mixture=Chemical; DTXSID=DTXSID9021138; Assay=Human Maximization Test; Endpoint=Concentration, one positive response; Response=0.025; Response_Unit=%; Species=Human; Route=Dermal; Reference=Kligman 1966; 5924293; 10.1038/jid.1966.159; URL_CompTox=https://comptox.epa.gov/dashboard/chemical/details/DTXSID9021138
NTP_ICE_skin_sensitization	Concentration, one positive response	0.02	%	Human	Dermal	-	In Vivo; HPPT2020WIP; Human Maximization Test	sheet=Data_invivo; excel_row=3085; Record_ID=skin_sensitization_invivo_805; Data_Type=In Vivo; Internal_Data_Source=HPPT2020WIP; Concentration=0.2; Concentration_Units=%; Mixture=Chemical; DTXSID=DTXSID9021138; Assay=Human Maximization Test; Endpoint=Concentration, one positive response; Response=0.02; Response_Unit=%; Species=Human; Route=Dermal; Reference=Kligman 1966; 5924293; 10.1038/jid.1966.159; URL_CompTox=https://comptox.epa.gov/dashboard/chemical/details/DTXSID9021138
NTP_ICE_skin_sensitization	Concentration, one positive response	0.05882	%	Human	Dermal	-	In Vivo; HPPT2020WIP; Human Maximization Test	sheet=Data_invivo; excel_row=3096; Record_ID=skin_sensitization_invivo_806; Data_Type=In Vivo; Internal_Data_Source=HPPT2020WIP; Concentration=1.0; Concentration_Units=%; Mixture=Chemical; DTXSID=DTXSID9021138; Assay=Human Maximization Test; Endpoint=Concentration, one positive response; Response=0.05882; Response_Unit=%; Species=Human; Route=Dermal; Reference=Kligman 1966; 5924293; 10.1038/jid.1966.159; URL_CompTox=https://comptox.epa.gov/dashboard/chemical/details/DTXSID9021138
NTP_ICE_skin_sensitization	Concentration, one positive response	0.2083	%	Human	Dermal	-	In Vivo; HPPT2020WIP; Human Maximization Test	sheet=Data_invivo; excel_row=3097; Record_ID=skin_sensitization_invivo_807; Data_Type=In Vivo; Internal_Data_Source=HPPT2020WIP; Concentration=5.0; Concentration_Units=%; Mixture=Chemical; DTXSID=DTXSID9021138; Assay=Human Maximization Test; Endpoint=Concentration, one positive response; Response=0.2083; Response_Unit=%; Species=Human; Route=Dermal; Reference=Kligman 1966; 5924293; 10.1038/jid.1966.159; URL_CompTox=https://comptox.epa.gov/dashboard/chemical/details/DTXSID9021138
NTP_ICE_skin_sensitization	Concentration, one positive response	0.2273	%	Human	Dermal	-	In Vivo; HPPT2020WIP; Human Maximization Test	sheet=Data_invivo; excel_row=3111; Record_ID=skin_sensitization_invivo_808; Data_Type=In Vivo; Internal_Data_Source=HPPT2020WIP; Concentration=5.0; Concentration_Units=%; Mixture=Chemical; DTXSID=DTXSID9021138; Assay=Human Maximization Test; Endpoint=Concentration, one positive response; Response=0.2273; Response_Unit=%; Species=Human; Route=Dermal; Reference=Kligman 1966; 5924293; 10.1038/jid.1966.159; URL_CompTox=https://comptox.epa.gov/dashboard/chemical/details/DTXSID9021138
NTP_ICE_skin_sensitization	Concentration, one positive response	0.4167	%	Human	Dermal	-	In Vivo; HPPT2020WIP; Human Maximization Test	sheet=Data_invivo; excel_row=3114; Record_ID=skin_sensitization_invivo_809; Data_Type=In Vivo; Internal_Data_Source=HPPT2020WIP; Concentration=10.0; Concentration_Units=%; Mixture=Chemical; DTXSID=DTXSID9021138; Assay=Human Maximization Test; Endpoint=Concentration, one positive response; Response=0.4167; Response_Unit=%; Species=Human; Route=Dermal; Reference=Kligman 1966; 5924293; 10.1038/jid.1966.159; URL_CompTox=https://comptox.epa.gov/dashboard/chemical/details/DTXSID9021138
NTP_ICE_skin_sensitization	Concentration, one positive response	0.009091	%	Human	Dermal	-	In Vivo; HPPT2020WIP; Human Repeat Insult Patch Test	sheet=Data_invivo; excel_row=3141; Record_ID=skin_sensitization_invivo_812; Data_Type=In Vivo; Internal_Data_Source=HPPT2020WIP; Concentration=0.1; Concentration_Units=%; Mixture=Chemical; DTXSID=DTXSID9021138; Assay=Human Repeat Insult Patch Test; Endpoint=Concentration, one positive response; Response=0.009091; Response_Unit=%; Species=Human; Route=Dermal; Reference=Marzulli and Maibach 1974; 4459237; 10.1016/0015-6264(74)90367-8\|Gerberick et al. 2001; 11526521; 10.1053/ajcd.2001.23926\|Akkan et al. 2003; Not available; Not available\|Griem et al. 2003; 14623479; 10.1016/j.yrtph.2003.07.001\|Schneider and Akkan 2004; 15135206; 10.1016/j.yrtph.2004.02.002\|Basketter et al. 2005; 16283904; 10.1111/j.0105-1873.2005.00707.x\|ICCVAM 2009; Not available; https://ntp.niehs.nih.gov/iccvam/docs/immunotox_docs/llna-ps/llnaperfstds.pdf; URL_CompTox=https://comptox.epa.gov/dashboard/chemical/details/DTXSID9021138
NTP_ICE_skin_sensitization	Concentration, one positive response	1.25	%	Human	Dermal	-	In Vivo; HPPT2020WIP; Human Maximization Test	sheet=Data_invivo; excel_row=3147; Record_ID=skin_sensitization_invivo_813; Data_Type=In Vivo; Internal_Data_Source=HPPT2020WIP; Concentration=25.0; Concentration_Units=%; Mixture=Chemical; DTXSID=DTXSID9021138; Assay=Human Maximization Test; Endpoint=Concentration, one positive response; Response=1.25; Response_Unit=%; Species=Human; Route=Dermal; Reference=Kligman 1966; 5924293; 10.1038/jid.1966.159; URL_CompTox=https://comptox.epa.gov/dashboard/chemical/details/DTXSID9021138
NTP_ICE_skin_sensitization	Concentration, one positive response	0.02128	%	Human	Dermal	-	In Vivo; HPPT2020WIP; Human Repeat Insult Patch Test	sheet=Data_invivo; excel_row=3156; Record_ID=skin_sensitization_invivo_814; Data_Type=In Vivo; Internal_Data_Source=HPPT2020WIP; Concentration=1.0; Concentration_Units=%; Mixture=Chemical; DTXSID=DTXSID9021138; Assay=Human Repeat Insult Patch Test; Endpoint=Concentration, one positive response; Response=0.02128; Response_Unit=%; Species=Human; Route=Dermal; Reference=Marzulli and Maibach 1974; 4459237; 10.1016/0015-6264(74)90367-8\|Gerberick et al. 2001; 11526521; 10.1053/ajcd.2001.23926\|Akkan et al. 2003; Not available; Not available\|Griem et al. 2003; 14623479; 10.1016/j.yrtph.2003.07.001\|Schneider and Akkan 2004; 15135206; 10.1016/j.yrtph.2004.02.002\|Basketter et al. 2005; 16283904; 10.1111/j.0105-1873.2005.00707.x\|ICCVAM 2009; Not available; https://ntp.niehs.nih.gov/iccvam/docs/immunotox_docs/llna-ps/llnaperfstds.pdf; URL_CompTox=https://comptox.epa.gov/dashboard/chemical/details/DTXSID9021138
NTP_ICE_skin_sensitization	Concentration, one positive response	0.001429	%	Human	Dermal	-	In Vivo; HPPT2020WIP; Human Repeat Insult Patch Test	sheet=Data_invivo; excel_row=3163; Record_ID=skin_sensitization_invivo_811; Data_Type=In Vivo; Internal_Data_Source=HPPT2020WIP; Concentration=0.01; Concentration_Units=%; Mixture=Chemical; DTXSID=DTXSID9021138; Assay=Human Repeat Insult Patch Test; Endpoint=Concentration, one positive response; Response=0.001429; Response_Unit=%; Species=Human; Route=Dermal; Reference=Marzulli and Maibach 1974; 4459237; 10.1016/0015-6264(74)90367-8\|Gerberick et al. 2001; 11526521; 10.1053/ajcd.2001.23926\|Akkan et al. 2003; Not available; Not available\|Griem et al. 2003; 14623479; 10.1016/j.yrtph.2003.07.001\|Schneider and Akkan 2004; 15135206; 10.1016/j.yrtph.2004.02.002\|Basketter et al. 2005; 16283904; 10.1111/j.0105-1873.2005.00707.x\|ICCVAM 2009; Not available; https://ntp.niehs.nih.gov/iccvam/docs/immunotox_docs/llna-ps/llnaperfstds.pdf; URL_CompTox=https://comptox.epa.gov/dashboard/chemical/details/DTXSID9021138
NTP_ICE_skin_sensitization	Depletion Cys	100	%	-	Dermal	-	In Vitro; DPRA2015; DPRA	sheet=Data_invitro; excel_row=1388; Record_ID=skin_sensitization_invitro_371; Data_Type=In Vitro; Internal_Data_Source=DPRA2015; Mixture=Chemical; DTXSID=DTXSID9021138; Assay=DPRA; Endpoint=Depletion Cys; Reported_Response=100; Reported_Response_Unit=%; Response=100; Response_Unit=%; Reference=Joint Research Centre of the European Union 2013; URL_CompTox=https://comptox.epa.gov/dashboard/chemical/details/DTXSID9021138
NTP_ICE_skin_sensitization	Depletion Cys	93	%	-	Dermal	-	In Vitro; DPRA2015; DPRA	sheet=Data_invitro; excel_row=1392; Record_ID=skin_sensitization_invitro_372; Data_Type=In Vitro; Internal_Data_Source=DPRA2015; Mixture=Chemical; DTXSID=DTXSID9021138; Assay=DPRA; Endpoint=Depletion Cys; Reported_Response=93; Reported_Response_Unit=%; Response=93; Response_Unit=%; Reference=Jaworska supp A 2013; 21993957; 10.14573/altex.2011.3.211; URL_CompTox=https://comptox.epa.gov/dashboard/chemical/details/DTXSID9021138
NTP_ICE_skin_sensitization	Depletion Cys	80.2	%	-	Dermal	-	In Vitro; DPRA2015; DPRA	sheet=Data_invitro; excel_row=1404; Record_ID=skin_sensitization_invitro_375; Data_Type=In Vitro; Internal_Data_Source=DPRA2015; Mixture=Chemical; DTXSID=DTXSID9021138; Assay=DPRA; Endpoint=Depletion Cys; Reported_Response=80.2; Reported_Response_Unit=%; Response=80.2; Response_Unit=%; Reference=Nukada et al. 2013; 23149339; 10.1016/j.tiv.2012.11.006\|Nukada personal communication (undated); URL_CompTox=https://comptox.epa.gov/dashboard/chemical/details/DTXSID9021138
NTP_ICE_skin_sensitization	Depletion Cys	99.8	%	-	Dermal	-	In Vitro; DPRA2015; DPRA	sheet=Data_invitro; excel_row=1548; Record_ID=skin_sensitization_invitro_434; Data_Type=In Vitro; Internal_Data_Source=DPRA2015; Mixture=Chemical; DTXSID=DTXSID9021138; Assay=DPRA; Endpoint=Depletion Cys; Reported_Response=99.8; Reported_Response_Unit=%; Response=99.8; Response_Unit=%; Reference=Bauch et al. 2011; 21669280; 10.1016/j.tiv.2011.05.030\|Bauch et al. 2012; 22659254; 10.1016/j.yrtph.2012.05.013; URL_CompTox=https://comptox.epa.gov/dashboard/chemical/details/DTXSID9021138
NTP_ICE_skin_sensitization	Depletion Cys	83.3	%	-	Dermal	-	In Vitro; DPRA2015; DPRA	sheet=Data_invitro; excel_row=1552; Record_ID=skin_sensitization_invitro_435; Data_Type=In Vitro; Internal_Data_Source=DPRA2015; Mixture=Chemical; DTXSID=DTXSID9021138; Assay=DPRA; Endpoint=Depletion Cys; Reported_Response=83.3; Reported_Response_Unit=%; Response=83.3; Response_Unit=%; Reference=Jaworska 2011; 23670904; 10.1002/jat.2869; URL_CompTox=https://comptox.epa.gov/dashboard/chemical/details/DTXSID9021138
NTP_ICE_skin_sensitization	Depletion Cys	92.3	%	-	Dermal	-	In Vitro; DPRA2015; DPRA	sheet=Data_invitro; excel_row=1556; Record_ID=skin_sensitization_invitro_436; Data_Type=In Vitro; Internal_Data_Source=DPRA2015; Mixture=Chemical; DTXSID=DTXSID9021138; Assay=DPRA; Endpoint=Depletion Cys; Reported_Response=92.3; Reported_Response_Unit=%; Response=92.3; Response_Unit=%; Reference=Joint Research Centre of the European Union 2013; URL_CompTox=https://comptox.epa.gov/dashboard/chemical/details/DTXSID9021138
NTP_ICE_skin_sensitization	Depletion Cys	85.1	%	-	Dermal	-	In Vitro; DPRA2015; DPRA	sheet=Data_invitro; excel_row=1560; Record_ID=skin_sensitization_invitro_437; Data_Type=In Vitro; Internal_Data_Source=DPRA2015; Mixture=Chemical; DTXSID=DTXSID9021138; Assay=DPRA; Endpoint=Depletion Cys; Reported_Response=85.1; Reported_Response_Unit=%; Response=85.1; Response_Unit=%; Reference=Joint Research Centre of the European Union 2013; URL_CompTox=https://comptox.epa.gov/dashboard/chemical/details/DTXSID9021138
NTP_ICE_skin_sensitization	Depletion Lys	29.9	%	-	Dermal	-	In Vitro; DPRA2015; DPRA	sheet=Data_invitro; excel_row=1387; Record_ID=skin_sensitization_invitro_371; Data_Type=In Vitro; Internal_Data_Source=DPRA2015; Mixture=Chemical; DTXSID=DTXSID9021138; Assay=DPRA; Endpoint=Depletion Lys; Reported_Response=29.9; Reported_Response_Unit=%; Response=29.9; Response_Unit=%; Reference=Joint Research Centre of the European Union 2013; URL_CompTox=https://comptox.epa.gov/dashboard/chemical/details/DTXSID9021138
NTP_ICE_skin_sensitization	Depletion Lys	23.5	%	-	Dermal	-	In Vitro; DPRA2015; DPRA	sheet=Data_invitro; excel_row=1391; Record_ID=skin_sensitization_invitro_372; Data_Type=In Vitro; Internal_Data_Source=DPRA2015; Mixture=Chemical; DTXSID=DTXSID9021138; Assay=DPRA; Endpoint=Depletion Lys; Reported_Response=23.5; Reported_Response_Unit=%; Response=23.5; Response_Unit=%; Reference=Jaworska supp A 2013; 21993957; 10.14573/altex.2011.3.211; URL_CompTox=https://comptox.epa.gov/dashboard/chemical/details/DTXSID9021138
NTP_ICE_skin_sensitization	Depletion Lys	11.5	%	-	Dermal	-	In Vitro; DPRA2015; DPRA	sheet=Data_invitro; excel_row=1403; Record_ID=skin_sensitization_invitro_375; Data_Type=In Vitro; Internal_Data_Source=DPRA2015; Mixture=Chemical; DTXSID=DTXSID9021138; Assay=DPRA; Endpoint=Depletion Lys; Reported_Response=11.5; Reported_Response_Unit=%; Response=11.5; Response_Unit=%; Reference=Nukada et al. 2013; 23149339; 10.1016/j.tiv.2012.11.006\|Nukada personal communication (undated); URL_CompTox=https://comptox.epa.gov/dashboard/chemical/details/DTXSID9021138
NTP_ICE_skin_sensitization	Depletion Lys	42.2	%	-	Dermal	-	In Vitro; DPRA2015; DPRA	sheet=Data_invitro; excel_row=1547; Record_ID=skin_sensitization_invitro_434; Data_Type=In Vitro; Internal_Data_Source=DPRA2015; Mixture=Chemical; DTXSID=DTXSID9021138; Assay=DPRA; Endpoint=Depletion Lys; Reported_Response=42.2; Reported_Response_Unit=%; Response=42.2; Response_Unit=%; Reference=Bauch et al. 2011; 21669280; 10.1016/j.tiv.2011.05.030\|Bauch et al. 2012; 22659254; 10.1016/j.yrtph.2012.05.013; URL_CompTox=https://comptox.epa.gov/dashboard/chemical/details/DTXSID9021138
NTP_ICE_skin_sensitization	Depletion Lys	37.5	%	-	Dermal	-	In Vitro; DPRA2015; DPRA	sheet=Data_invitro; excel_row=1551; Record_ID=skin_sensitization_invitro_435; Data_Type=In Vitro; Internal_Data_Source=DPRA2015; Mixture=Chemical; DTXSID=DTXSID9021138; Assay=DPRA; Endpoint=Depletion Lys; Reported_Response=37.5; Reported_Response_Unit=%; Response=37.5; Response_Unit=%; Reference=Jaworska 2011; 23670904; 10.1002/jat.2869; URL_CompTox=https://comptox.epa.gov/dashboard/chemical/details/DTXSID9021138
NTP_ICE_skin_sensitization	Depletion Lys	14.9	%	-	Dermal	-	In Vitro; DPRA2015; DPRA	sheet=Data_invitro; excel_row=1555; Record_ID=skin_sensitization_invitro_436; Data_Type=In Vitro; Internal_Data_Source=DPRA2015; Mixture=Chemical; DTXSID=DTXSID9021138; Assay=DPRA; Endpoint=Depletion Lys; Reported_Response=14.9; Reported_Response_Unit=%; Response=14.9; Response_Unit=%; Reference=Joint Research Centre of the European Union 2013; URL_CompTox=https://comptox.epa.gov/dashboard/chemical/details/DTXSID9021138
NTP_ICE_skin_sensitization	Depletion Lys	19.6	%	-	Dermal	-	In Vitro; DPRA2015; DPRA	sheet=Data_invitro; excel_row=1559; Record_ID=skin_sensitization_invitro_437; Data_Type=In Vitro; Internal_Data_Source=DPRA2015; Mixture=Chemical; DTXSID=DTXSID9021138; Assay=DPRA; Endpoint=Depletion Lys; Reported_Response=19.600000000000001; Reported_Response_Unit=%; Response=19.6; Response_Unit=%; Reference=Joint Research Centre of the European Union 2013; URL_CompTox=https://comptox.epa.gov/dashboard/chemical/details/DTXSID9021138
NTP_ICE_skin_sensitization	Depletion Lys + Cys	64.95	%	-	Dermal	-	In Vitro; DPRA2015; DPRA	sheet=Data_invitro; excel_row=1389; Record_ID=skin_sensitization_invitro_371; Data_Type=In Vitro; Internal_Data_Source=DPRA2015; Mixture=Chemical; DTXSID=DTXSID9021138; Assay=DPRA; Endpoint=Depletion Lys + Cys; Reported_Response=64.95; Reported_Response_Unit=%; Response=64.95; Response_Unit=%; Reference=Joint Research Centre of the European Union 2013; URL_CompTox=https://comptox.epa.gov/dashboard/chemical/details/DTXSID9021138
NTP_ICE_skin_sensitization	Depletion Lys + Cys	58.25	%	-	Dermal	-	In Vitro; DPRA2015; DPRA	sheet=Data_invitro; excel_row=1393; Record_ID=skin_sensitization_invitro_372; Data_Type=In Vitro; Internal_Data_Source=DPRA2015; Mixture=Chemical; DTXSID=DTXSID9021138; Assay=DPRA; Endpoint=Depletion Lys + Cys; Reported_Response=58.25; Reported_Response_Unit=%; Response=58.25; Response_Unit=%; Reference=Jaworska supp A 2013; 21993957; 10.14573/altex.2011.3.211; URL_CompTox=https://comptox.epa.gov/dashboard/chemical/details/DTXSID9021138
NTP_ICE_skin_sensitization	Depletion Lys + Cys	46	%	-	Dermal	-	In Vitro; DPRA2015; DPRA	sheet=Data_invitro; excel_row=1405; Record_ID=skin_sensitization_invitro_375; Data_Type=In Vitro; Internal_Data_Source=DPRA2015; Mixture=Chemical; DTXSID=DTXSID9021138; Assay=DPRA; Endpoint=Depletion Lys + Cys; Reported_Response=46; Reported_Response_Unit=%; Response=46; Response_Unit=%; Reference=Nukada et al. 2013; 23149339; 10.1016/j.tiv.2012.11.006\|Nukada personal communication (undated); URL_CompTox=https://comptox.epa.gov/dashboard/chemical/details/DTXSID9021138
NTP_ICE_skin_sensitization	Depletion Lys + Cys	71	%	-	Dermal	-	In Vitro; DPRA2015; DPRA	sheet=Data_invitro; excel_row=1549; Record_ID=skin_sensitization_invitro_434; Data_Type=In Vitro; Internal_Data_Source=DPRA2015; Mixture=Chemical; DTXSID=DTXSID9021138; Assay=DPRA; Endpoint=Depletion Lys + Cys; Reported_Response=71; Reported_Response_Unit=%; Response=71; Response_Unit=%; Reference=Bauch et al. 2011; 21669280; 10.1016/j.tiv.2011.05.030\|Bauch et al. 2012; 22659254; 10.1016/j.yrtph.2012.05.013; URL_CompTox=https://comptox.epa.gov/dashboard/chemical/details/DTXSID9021138
NTP_ICE_skin_sensitization	Depletion Lys + Cys	60.4	%	-	Dermal	-	In Vitro; DPRA2015; DPRA	sheet=Data_invitro; excel_row=1553; Record_ID=skin_sensitization_invitro_435; Data_Type=In Vitro; Internal_Data_Source=DPRA2015; Mixture=Chemical; DTXSID=DTXSID9021138; Assay=DPRA; Endpoint=Depletion Lys + Cys; Reported_Response=60.4; Reported_Response_Unit=%; Response=60.4; Response_Unit=%; Reference=Jaworska 2011; 23670904; 10.1002/jat.2869; URL_CompTox=https://comptox.epa.gov/dashboard/chemical/details/DTXSID9021138
NTP_ICE_skin_sensitization	Depletion Lys + Cys	53.6	%	-	Dermal	-	In Vitro; DPRA2015; DPRA	sheet=Data_invitro; excel_row=1557; Record_ID=skin_sensitization_invitro_436; Data_Type=In Vitro; Internal_Data_Source=DPRA2015; Mixture=Chemical; DTXSID=DTXSID9021138; Assay=DPRA; Endpoint=Depletion Lys + Cys; Reported_Response=53.6; Reported_Response_Unit=%; Response=53.6; Response_Unit=%; Reference=Joint Research Centre of the European Union 2013; URL_CompTox=https://comptox.epa.gov/dashboard/chemical/details/DTXSID9021138
NTP_ICE_skin_sensitization	Depletion Lys + Cys	52.35	%	-	Dermal	-	In Vitro; DPRA2015; DPRA	sheet=Data_invitro; excel_row=1561; Record_ID=skin_sensitization_invitro_437; Data_Type=In Vitro; Internal_Data_Source=DPRA2015; Mixture=Chemical; DTXSID=DTXSID9021138; Assay=DPRA; Endpoint=Depletion Lys + Cys; Reported_Response=52.35; Reported_Response_Unit=%; Response=52.35; Response_Unit=%; Reference=Joint Research Centre of the European Union 2013; URL_CompTox=https://comptox.epa.gov/dashboard/chemical/details/DTXSID9021138
NTP_ICE_skin_sensitization	EC1.5	10.1	uM	-	Dermal	-	In Vitro; KeratinoSens2015; KeratinoSens	sheet=Data_invitro; excel_row=4349; Record_ID=skin_sensitization_invitro_1011; Data_Type=In Vitro; Internal_Data_Source=KeratinoSens2015; Mixture=Chemical; DTXSID=DTXSID9021138; Assay=KeratinoSens; Endpoint=EC1.5; Reported_Response=10.1; Reported_Response_Unit=uM; Response=10.1; Response_Unit=uM; Reference=Natsch et al. 2011; 22023385; 10.1021/tx2003678; URL_CompTox=https://comptox.epa.gov/dashboard/chemical/details/DTXSID9021138
NTP_ICE_skin_sensitization	EC1.5	11.3	uM	-	Dermal	-	In Vitro; KeratinoSens2015; KeratinoSens	sheet=Data_invitro; excel_row=4353; Record_ID=skin_sensitization_invitro_995; Data_Type=In Vitro; Internal_Data_Source=KeratinoSens2015; Mixture=Chemical; DTXSID=DTXSID9021138; Assay=KeratinoSens; Endpoint=EC1.5; Reported_Response=11.3; Reported_Response_Unit=uM; Response=11.3; Response_Unit=uM; Reference=Joint Research Centre of the European Union 2014; URL_CompTox=https://comptox.epa.gov/dashboard/chemical/details/DTXSID9021138
NTP_ICE_skin_sensitization	EC1.5	12.7	uM	-	Dermal	-	In Vitro; KeratinoSens2015; KeratinoSens	sheet=Data_invitro; excel_row=4355; Record_ID=skin_sensitization_invitro_1004; Data_Type=In Vitro; Internal_Data_Source=KeratinoSens2015; Mixture=Chemical; DTXSID=DTXSID9021138; Assay=KeratinoSens; Endpoint=EC1.5; Reported_Response=12.7; Reported_Response_Unit=uM; Response=12.7; Response_Unit=uM; Reference=Joint Research Centre of the European Union 2014; URL_CompTox=https://comptox.epa.gov/dashboard/chemical/details/DTXSID9021138
NTP_ICE_skin_sensitization	EC1.5	13.55	uM	-	Dermal	-	In Vitro; KeratinoSens2015; KeratinoSens	sheet=Data_invitro; excel_row=4357; Record_ID=skin_sensitization_invitro_994; Data_Type=In Vitro; Internal_Data_Source=KeratinoSens2015; Mixture=Chemical; DTXSID=DTXSID9021138; Assay=KeratinoSens; Endpoint=EC1.5; Reported_Response=13.55; Reported_Response_Unit=uM; Response=13.55; Response_Unit=uM; Reference=Joint Research Centre of the European Union 2014; URL_CompTox=https://comptox.epa.gov/dashboard/chemical/details/DTXSID9021138
NTP_ICE_skin_sensitization	EC1.5	15.83	uM	-	Dermal	-	In Vitro; KeratinoSens2015; KeratinoSens	sheet=Data_invitro; excel_row=4359; Record_ID=skin_sensitization_invitro_997; Data_Type=In Vitro; Internal_Data_Source=KeratinoSens2015; Mixture=Chemical; DTXSID=DTXSID9021138; Assay=KeratinoSens; Endpoint=EC1.5; Reported_Response=15.83; Reported_Response_Unit=uM; Response=15.83; Response_Unit=uM; Reference=Joint Research Centre of the European Union 2014; URL_CompTox=https://comptox.epa.gov/dashboard/chemical/details/DTXSID9021138
NTP_ICE_skin_sensitization	EC1.5	25.65	uM	-	Dermal	-	In Vitro; KeratinoSens2015; KeratinoSens	sheet=Data_invitro; excel_row=4361; Record_ID=skin_sensitization_invitro_1005; Data_Type=In Vitro; Internal_Data_Source=KeratinoSens2015; Mixture=Chemical; DTXSID=DTXSID9021138; Assay=KeratinoSens; Endpoint=EC1.5; Reported_Response=25.65; Reported_Response_Unit=uM; Response=25.65; Response_Unit=uM; Reference=Joint Research Centre of the European Union 2014; URL_CompTox=https://comptox.epa.gov/dashboard/chemical/details/DTXSID9021138
NTP_ICE_skin_sensitization	EC1.5	3.2	uM	-	Dermal	-	In Vitro; KeratinoSens2015; KeratinoSens	sheet=Data_invitro; excel_row=4363; Record_ID=skin_sensitization_invitro_1003; Data_Type=In Vitro; Internal_Data_Source=KeratinoSens2015; Mixture=Chemical; DTXSID=DTXSID9021138; Assay=KeratinoSens; Endpoint=EC1.5; Reported_Response=3.2; Reported_Response_Unit=uM; Response=3.2; Response_Unit=uM; Reference=Joint Research Centre of the European Union 2014; URL_CompTox=https://comptox.epa.gov/dashboard/chemical/details/DTXSID9021138
NTP_ICE_skin_sensitization	EC1.5	3.6	uM	-	Dermal	-	In Vitro; KeratinoSens2015; KeratinoSens	sheet=Data_invitro; excel_row=4364; Record_ID=skin_sensitization_invitro_1014; Data_Type=In Vitro; Internal_Data_Source=KeratinoSens2015; Mixture=Chemical; DTXSID=DTXSID9021138; Assay=KeratinoSens; Endpoint=EC1.5; Reported_Response=3.6; Reported_Response_Unit=uM; Response=3.6; Response_Unit=uM; Reference=Joint Research Centre of the European Union 2014; URL_CompTox=https://comptox.epa.gov/dashboard/chemical/details/DTXSID9021138
NTP_ICE_skin_sensitization	EC1.5	5	uM	-	Dermal	-	In Vitro; KeratinoSens2015; KeratinoSens	sheet=Data_invitro; excel_row=4371; Record_ID=skin_sensitization_invitro_1016; Data_Type=In Vitro; Internal_Data_Source=KeratinoSens2015; Mixture=Chemical; DTXSID=DTXSID9021138; Assay=KeratinoSens; Endpoint=EC1.5; Reported_Response=5; Reported_Response_Unit=uM; Response=5; Response_Unit=uM; Reference=Bauch et al. 2011; 21669280; 10.1016/j.tiv.2011.05.030\|Bauch et al. 2012; 22659254; 10.1016/j.yrtph.2012.05.013; URL_CompTox=https://comptox.epa.gov/dashboard/chemical/details/DTXSID9021138
NTP_ICE_skin_sensitization	EC1.5	5.015	uM	-	Dermal	-	In Vitro; CE_KeratinoSense2018; KeratinoSens	sheet=Data_invitro; excel_row=4374; Record_ID=skin_sensitization_invitro_1017; Data_Type=In Vitro; Internal_Data_Source=CE_KeratinoSense2018; Mixture=Chemical; DTXSID=DTXSID9021138; Assay=KeratinoSens; Endpoint=EC1.5; Reported_Response=5.0149999999999997; Reported_Response_Unit=uM; Response=5.015; Response_Unit=uM; Reference=Emter et al. 2010; 20307559; 10.1016/j.taap.2010.03.009\|Natsch et al. 2013; 23576290; 10.1002/jat.2868\|Urbisch et al. 2015; 25541156; 10.1016/j.yrtph.2014.12.008; URL_CompTox=https://comptox.epa.gov/dashboard/chemical/details/DTXSID9021138
NTP_ICE_skin_sensitization	EC1.5	5.2	uM	-	Dermal	-	In Vitro; KeratinoSens2015; KeratinoSens	sheet=Data_invitro; excel_row=4377; Record_ID=skin_sensitization_invitro_999; Data_Type=In Vitro; Internal_Data_Source=KeratinoSens2015; Mixture=Chemical; DTXSID=DTXSID9021138; Assay=KeratinoSens; Endpoint=EC1.5; Reported_Response=5.2; Reported_Response_Unit=uM; Response=5.2; Response_Unit=uM; Reference=Joint Research Centre of the European Union 2014; URL_CompTox=https://comptox.epa.gov/dashboard/chemical/details/DTXSID9021138
NTP_ICE_skin_sensitization	EC1.5	5.56	uM	-	Dermal	-	In Vitro; KeratinoSens2015; KeratinoSens	sheet=Data_invitro; excel_row=4379; Record_ID=skin_sensitization_invitro_1001; Data_Type=In Vitro; Internal_Data_Source=KeratinoSens2015; Mixture=Chemical; DTXSID=DTXSID9021138; Assay=KeratinoSens; Endpoint=EC1.5; Reported_Response=5.56; Reported_Response_Unit=uM; Response=5.56; Response_Unit=uM; Reference=Joint Research Centre of the European Union 2014; URL_CompTox=https://comptox.epa.gov/dashboard/chemical/details/DTXSID9021138
NTP_ICE_skin_sensitization	EC1.5	6	uM	-	Dermal	-	In Vitro; KeratinoSens2015; KeratinoSens	sheet=Data_invitro; excel_row=4382; Record_ID=skin_sensitization_invitro_1009; Data_Type=In Vitro; Internal_Data_Source=KeratinoSens2015; Mixture=Chemical; DTXSID=DTXSID9021138; Assay=KeratinoSens; Endpoint=EC1.5; Reported_Response=6; Reported_Response_Unit=uM; Response=6; Response_Unit=uM; Reference=Natsch et al. 2011; 22023385; 10.1021/tx2003678; URL_CompTox=https://comptox.epa.gov/dashboard/chemical/details/DTXSID9021138
NTP_ICE_skin_sensitization	EC1.5	6.18	uM	-	Dermal	-	In Vitro; KeratinoSens2015; KeratinoSens	sheet=Data_invitro; excel_row=4384; Record_ID=skin_sensitization_invitro_1002; Data_Type=In Vitro; Internal_Data_Source=KeratinoSens2015; Mixture=Chemical; DTXSID=DTXSID9021138; Assay=KeratinoSens; Endpoint=EC1.5; Reported_Response=6.18; Reported_Response_Unit=uM; Response=6.18; Response_Unit=uM; Reference=Joint Research Centre of the European Union 2014; URL_CompTox=https://comptox.epa.gov/dashboard/chemical/details/DTXSID9021138
NTP_ICE_skin_sensitization	EC1.5	6.38	uM	-	Dermal	-	In Vitro; KeratinoSens2015; KeratinoSens	sheet=Data_invitro; excel_row=4388; Record_ID=skin_sensitization_invitro_1000; Data_Type=In Vitro; Internal_Data_Source=KeratinoSens2015; Mixture=Chemical; DTXSID=DTXSID9021138; Assay=KeratinoSens; Endpoint=EC1.5; Reported_Response=6.38; Reported_Response_Unit=uM; Response=6.38; Response_Unit=uM; Reference=Joint Research Centre of the European Union 2014; URL_CompTox=https://comptox.epa.gov/dashboard/chemical/details/DTXSID9021138
NTP_ICE_skin_sensitization	EC1.5	6.4	uM	-	Dermal	-	In Vitro; KeratinoSens2015; KeratinoSens	sheet=Data_invitro; excel_row=4390; Record_ID=skin_sensitization_invitro_1019; Data_Type=In Vitro; Internal_Data_Source=KeratinoSens2015; Mixture=Chemical; DTXSID=DTXSID9021138; Assay=KeratinoSens; Endpoint=EC1.5; Reported_Response=6.4; Reported_Response_Unit=uM; Response=6.4; Response_Unit=uM; Reference=Joint Research Centre of the European Union 2014; URL_CompTox=https://comptox.epa.gov/dashboard/chemical/details/DTXSID9021138
NTP_ICE_skin_sensitization	EC1.5	7.3	uM	-	Dermal	-	In Vitro; KeratinoSens2015; KeratinoSens	sheet=Data_invitro; excel_row=4401; Record_ID=skin_sensitization_invitro_998; Data_Type=In Vitro; Internal_Data_Source=KeratinoSens2015; Mixture=Chemical; DTXSID=DTXSID9021138; Assay=KeratinoSens; Endpoint=EC1.5; Reported_Response=7.3; Reported_Response_Unit=uM; Response=7.3; Response_Unit=uM; Reference=Joint Research Centre of the European Union 2014; URL_CompTox=https://comptox.epa.gov/dashboard/chemical/details/DTXSID9021138
NTP_ICE_skin_sensitization	EC1.5	8.39	uM	-	Dermal	-	In Vitro; KeratinoSens2015; KeratinoSens	sheet=Data_invitro; excel_row=4404; Record_ID=skin_sensitization_invitro_996; Data_Type=In Vitro; Internal_Data_Source=KeratinoSens2015; Mixture=Chemical; DTXSID=DTXSID9021138; Assay=KeratinoSens; Endpoint=EC1.5; Reported_Response=8.39; Reported_Response_Unit=uM; Response=8.39; Response_Unit=uM; Reference=Joint Research Centre of the European Union 2014; URL_CompTox=https://comptox.epa.gov/dashboard/chemical/details/DTXSID9021138
NTP_ICE_skin_sensitization	EC1.5	8.4	uM	-	Dermal	-	In Vitro; KeratinoSens2015; KeratinoSens	sheet=Data_invitro; excel_row=4407; Record_ID=skin_sensitization_invitro_1008; Data_Type=In Vitro; Internal_Data_Source=KeratinoSens2015; Mixture=Chemical; DTXSID=DTXSID9021138; Assay=KeratinoSens; Endpoint=EC1.5; Reported_Response=8.4; Reported_Response_Unit=uM; Response=8.4; Response_Unit=uM; Reference=Natsch et al. 2011; 22023385; 10.1021/tx2003678; URL_CompTox=https://comptox.epa.gov/dashboard/chemical/details/DTXSID9021138
NTP_ICE_skin_sensitization	EC1.5	8.8	uM	-	Dermal	-	In Vitro; KeratinoSens2015; KeratinoSens	sheet=Data_invitro; excel_row=4454; Record_ID=skin_sensitization_invitro_992; Data_Type=In Vitro; Internal_Data_Source=KeratinoSens2015; Mixture=Chemical; DTXSID=DTXSID9021138; Assay=KeratinoSens; Endpoint=EC1.5; Reported_Response=8.8000000000000007; Reported_Response_Unit=uM; Response=8.8; Response_Unit=uM; Reference=Joint Research Centre of the European Union 2014; URL_CompTox=https://comptox.epa.gov/dashboard/chemical/details/DTXSID9021138
NTP_ICE_skin_sensitization	EC1.5	9.16	uM	-	Dermal	-	In Vitro; KeratinoSens2015; KeratinoSens	sheet=Data_invitro; excel_row=4455; Record_ID=skin_sensitization_invitro_1006; Data_Type=In Vitro; Internal_Data_Source=KeratinoSens2015; Mixture=Chemical; DTXSID=DTXSID9021138; Assay=KeratinoSens; Endpoint=EC1.5; Reported_Response=9.16; Reported_Response_Unit=uM; Response=9.16; Response_Unit=uM; Reference=Joint Research Centre of the European Union 2014; URL_CompTox=https://comptox.epa.gov/dashboard/chemical/details/DTXSID9021138
NTP_ICE_skin_sensitization	EC1.5	9.9	uM	-	Dermal	-	In Vitro; KeratinoSens2015; KeratinoSens	sheet=Data_invitro; excel_row=4456; Record_ID=skin_sensitization_invitro_1020; Data_Type=In Vitro; Internal_Data_Source=KeratinoSens2015; Mixture=Chemical; DTXSID=DTXSID9021138; Assay=KeratinoSens; Endpoint=EC1.5; Reported_Response=9.9; Reported_Response_Unit=uM; Response=9.9; Response_Unit=uM; Reference=Natsch et al. 2011; 22023385; 10.1021/tx2003678; URL_CompTox=https://comptox.epa.gov/dashboard/chemical/details/DTXSID9021138
NTP_ICE_skin_sensitization	EC1.5	<53.05	uM	-	Dermal	-	In Vitro; Urbisch_SkinSensitization2020; LuSens	sheet=Data_invitro; excel_row=7613; Record_ID=skin_sensitization_invitro_1855; Data_Type=In Vitro; Internal_Data_Source=Urbisch_SkinSensitization2020; Mixture=Chemical; DTXSID=DTXSID9021138; Assay=LuSens; Endpoint=EC1.5; Response_Modifier=<; Reported_Response_Modifier=<; Reported_Response=53.05; Reported_Response_Unit=uM; Response=53.05; Response_Unit=uM; Reference=Urbisch et al. 2015; 25541156; 10.1016/j.yrtph.2014.12.008; URL_CompTox=https://comptox.epa.gov/dashboard/chemical/details/DTXSID9021138
NTP_ICE_skin_sensitization	EC3	46.74	uM	-	Dermal	-	In Vitro; CE_KeratinoSense2018; KeratinoSens	sheet=Data_invitro; excel_row=4458; Record_ID=skin_sensitization_invitro_1017; Data_Type=In Vitro; Internal_Data_Source=CE_KeratinoSense2018; Mixture=Chemical; DTXSID=DTXSID9021138; Assay=KeratinoSens; Endpoint=EC3; Reported_Response=46.743000000000002; Reported_Response_Unit=uM; Response=46.74; Response_Unit=uM; Reference=Emter et al. 2010; 20307559; 10.1016/j.taap.2010.03.009\|Natsch et al. 2013; 23576290; 10.1002/jat.2868\|Urbisch et al. 2015; 25541156; 10.1016/j.yrtph.2014.12.008; URL_CompTox=https://comptox.epa.gov/dashboard/chemical/details/DTXSID9021138
NTP_ICE_skin_sensitization	EC3	0.11	%	Mouse	Dermal	-	In Vivo; LLNA2013; LLNA	sheet=Data_invivo; excel_row=12861; Record_ID=skin_sensitization_invivo_488; Data_Type=In Vivo; Internal_Data_Source=LLNA2013; Mixture=Chemical; DTXSID=DTXSID9021138; Assay=LLNA; Endpoint=EC3; Response=0.11; Response_Unit=%; Species=Mouse; Route=Dermal; Reference=ICCVAM 2009; Not available; https://ntp.niehs.nih.gov/iccvam/docs/immunotox_docs/llna-ps/llnaperfstds.pdf; URL_CompTox=https://comptox.epa.gov/dashboard/chemical/details/DTXSID9021138
NTP_ICE_skin_sensitization	EC3	0.1	%	Mouse	Dermal	-	In Vivo; LLNAdb2013; LLNA	sheet=Data_invivo; excel_row=13547; Record_ID=skin_sensitization_invivo_3755; Data_Type=In Vivo; Internal_Data_Source=LLNAdb2013; Mixture=Chemical; DTXSID=DTXSID9021138; Assay=LLNA; Endpoint=EC3; Response=0.1; Response_Unit=%; Species=Mouse; Route=Dermal; Reference=Gerberick et al. 2004; 15209809; 10.1111/j.0105-1873.2004.00290.x; URL_CompTox=https://comptox.epa.gov/dashboard/chemical/details/DTXSID9021138
NTP_ICE_skin_sensitization	EC3	2.2	%	Mouse	Dermal	-	In Vivo; LLNAdb2013; LLNA	sheet=Data_invivo; excel_row=13548; Record_ID=skin_sensitization_invivo_3757; Data_Type=In Vivo; Internal_Data_Source=LLNAdb2013; Mixture=Chemical; DTXSID=DTXSID9021138; Assay=LLNA; Endpoint=EC3; Response=2.2; Response_Unit=%; Species=Mouse; Route=Dermal; Reference=Kimber et al. 1991; 1998208; 10.1016/0378-4274(91)90135-s; URL_CompTox=https://comptox.epa.gov/dashboard/chemical/details/DTXSID9021138
NTP_ICE_skin_sensitization	EC3	0.4	%	Mouse	Dermal	-	In Vivo; LLNAdb2013; LLNA	sheet=Data_invivo; excel_row=13550; Record_ID=skin_sensitization_invivo_3759; Data_Type=In Vivo; Internal_Data_Source=LLNAdb2013; Mixture=Chemical; DTXSID=DTXSID9021138; Assay=LLNA; Endpoint=EC3; Response=0.4; Response_Unit=%; Species=Mouse; Route=Dermal; Reference=Kimber et al. 1991; 1998208; 10.1016/0378-4274(91)90135-s; URL_CompTox=https://comptox.epa.gov/dashboard/chemical/details/DTXSID9021138
NTP_ICE_skin_sensitization	EC3	0.001	%	Mouse	Dermal	-	In Vivo; LLNAdb2013; LLNA	sheet=Data_invivo; excel_row=13552; Record_ID=skin_sensitization_invivo_3761; Data_Type=In Vivo; Internal_Data_Source=LLNAdb2013; Mixture=Chemical; DTXSID=DTXSID9021138; Assay=LLNA; Endpoint=EC3; Response=1.00E-03; Response_Unit=%; Species=Mouse; Route=Dermal; Reference=Kimber et al. 1991; 1998208; 10.1016/0378-4274(91)90135-s; URL_CompTox=https://comptox.epa.gov/dashboard/chemical/details/DTXSID9021138
NTP_ICE_skin_sensitization	EC3	0.16	%	Mouse	Dermal	-	In Vivo; LLNAdb2013; LLNA	sheet=Data_invivo; excel_row=13554; Record_ID=skin_sensitization_invivo_3763; Data_Type=In Vivo; Internal_Data_Source=LLNAdb2013; Mixture=Chemical; DTXSID=DTXSID9021138; Assay=LLNA; Endpoint=EC3; Response=0.16; Response_Unit=%; Species=Mouse; Route=Dermal; Reference=Gerberick et al. 2005; 16536334; Not available; URL_CompTox=https://comptox.epa.gov/dashboard/chemical/details/DTXSID9021138
NTP_ICE_skin_sensitization	EC3	0.2	%	Mouse	Dermal	-	In Vivo; LLNAdb2013; LLNA	sheet=Data_invivo; excel_row=13555; Record_ID=skin_sensitization_invivo_3766; Data_Type=In Vivo; Internal_Data_Source=LLNAdb2013; Mixture=Chemical; DTXSID=DTXSID9021138; Assay=LLNA; Endpoint=EC3; Response=0.2; Response_Unit=%; Species=Mouse; Route=Dermal; Reference=Kimber et al. 1991; 1998208; 10.1016/0378-4274(91)90135-s; URL_CompTox=https://comptox.epa.gov/dashboard/chemical/details/DTXSID9021138
NTP_ICE_skin_sensitization	EC3	0.07	%	Mouse	Dermal	-	In Vivo; LLNAdb2013; LLNA	sheet=Data_invivo; excel_row=13559; Record_ID=skin_sensitization_invivo_3774; Data_Type=In Vivo; Internal_Data_Source=LLNAdb2013; Mixture=Chemical; DTXSID=DTXSID9021138; Assay=LLNA; Endpoint=EC3; Response=7.00E-02; Response_Unit=%; Species=Mouse; Route=Dermal; Reference=Warbrick et al. 1999; 10439339; 10.1002/(sici)1099-1263(199907/08)19:4<255::aid-jat573>3.0.co;2-s; URL_CompTox=https://comptox.epa.gov/dashboard/chemical/details/DTXSID9021138
NTP_ICE_skin_sensitization	EC3	0.13	%	Mouse	Dermal	-	In Vivo; LLNAdb2013; LLNA	sheet=Data_invivo; excel_row=13563; Record_ID=skin_sensitization_invivo_3778; Data_Type=In Vivo; Internal_Data_Source=LLNAdb2013; Mixture=Chemical; DTXSID=DTXSID9021138; Assay=LLNA; Endpoint=EC3; Response=0.13; Response_Unit=%; Species=Mouse; Route=Dermal; Reference=White et al. 2006; 17014438; 10.1111/j.1365-2222.2006.02561.x; URL_CompTox=https://comptox.epa.gov/dashboard/chemical/details/DTXSID9021138
NTP_ICE_skin_sensitization	EC3	0.15	%	Mouse	Dermal	-	In Vivo; LLNAdb2013; LLNA	sheet=Data_invivo; excel_row=13565; Record_ID=skin_sensitization_invivo_3780; Data_Type=In Vivo; Internal_Data_Source=LLNAdb2013; Mixture=Chemical; DTXSID=DTXSID9021138; Assay=LLNA; Endpoint=EC3; Response=0.15; Response_Unit=%; Species=Mouse; Route=Dermal; Reference=Warbrick et al. 1999; 10439339; 10.1002/(sici)1099-1263(199907/08)19:4<255::aid-jat573>3.0.co;2-s; URL_CompTox=https://comptox.epa.gov/dashboard/chemical/details/DTXSID9021138
NTP_ICE_skin_sensitization	EC3	0.05	%	Mouse	Dermal	-	In Vivo; LLNAdb2013; LLNA	sheet=Data_invivo; excel_row=13567; Record_ID=skin_sensitization_invivo_3782; Data_Type=In Vivo; Internal_Data_Source=LLNAdb2013; Mixture=Chemical; DTXSID=DTXSID9021138; Assay=LLNA; Endpoint=EC3; Response=0.05; Response_Unit=%; Species=Mouse; Route=Dermal; Reference=Montelius et al. 1994; Not available; Not available; URL_CompTox=https://comptox.epa.gov/dashboard/chemical/details/DTXSID9021138
NTP_ICE_skin_sensitization	EC3	0.1	%	Mouse	Dermal	-	In Vivo; LLNAdb2013; LLNA	sheet=Data_invivo; excel_row=13547; Record_ID=skin_sensitization_invivo_3755; Data_Type=In Vivo; Internal_Data_Source=LLNAdb2013; Mixture=Chemical; DTXSID=DTXSID9021138; Assay=LLNA; Endpoint=EC3; Response=0.1; Response_Unit=%; Species=Mouse; Route=Dermal; Reference=Gerberick et al. 2004; 15209809; 10.1111/j.0105-1873.2004.00290.x; URL_CompTox=https://comptox.epa.gov/dashboard/chemical/details/DTXSID9021138
NTP_ICE_skin_sensitization	EC3	2.2	%	Mouse	Dermal	-	In Vivo; LLNAdb2013; LLNA	sheet=Data_invivo; excel_row=13548; Record_ID=skin_sensitization_invivo_3757; Data_Type=In Vivo; Internal_Data_Source=LLNAdb2013; Mixture=Chemical; DTXSID=DTXSID9021138; Assay=LLNA; Endpoint=EC3; Response=2.2; Response_Unit=%; Species=Mouse; Route=Dermal; Reference=Kimber et al. 1991; 1998208; 10.1016/0378-4274(91)90135-s; URL_CompTox=https://comptox.epa.gov/dashboard/chemical/details/DTXSID9021138
NTP_ICE_skin_sensitization	EC3	0.4	%	Mouse	Dermal	-	In Vivo; LLNAdb2013; LLNA	sheet=Data_invivo; excel_row=13550; Record_ID=skin_sensitization_invivo_3759; Data_Type=In Vivo; Internal_Data_Source=LLNAdb2013; Mixture=Chemical; DTXSID=DTXSID9021138; Assay=LLNA; Endpoint=EC3; Response=0.4; Response_Unit=%; Species=Mouse; Route=Dermal; Reference=Kimber et al. 1991; 1998208; 10.1016/0378-4274(91)90135-s; URL_CompTox=https://comptox.epa.gov/dashboard/chemical/details/DTXSID9021138
NTP_ICE_skin_sensitization	EC3	0.001	%	Mouse	Dermal	-	In Vivo; LLNAdb2013; LLNA	sheet=Data_invivo; excel_row=13552; Record_ID=skin_sensitization_invivo_3761; Data_Type=In Vivo; Internal_Data_Source=LLNAdb2013; Mixture=Chemical; DTXSID=DTXSID9021138; Assay=LLNA; Endpoint=EC3; Response=1.00E-03; Response_Unit=%; Species=Mouse; Route=Dermal; Reference=Kimber et al. 1991; 1998208; 10.1016/0378-4274(91)90135-s; URL_CompTox=https://comptox.epa.gov/dashboard/chemical/details/DTXSID9021138
NTP_ICE_skin_sensitization	EC3	0.16	%	Mouse	Dermal	-	In Vivo; LLNAdb2013; LLNA	sheet=Data_invivo; excel_row=13554; Record_ID=skin_sensitization_invivo_3763; Data_Type=In Vivo; Internal_Data_Source=LLNAdb2013; Mixture=Chemical; DTXSID=DTXSID9021138; Assay=LLNA; Endpoint=EC3; Response=0.16; Response_Unit=%; Species=Mouse; Route=Dermal; Reference=Gerberick et al. 2005; 16536334; Not available; URL_CompTox=https://comptox.epa.gov/dashboard/chemical/details/DTXSID9021138
NTP_ICE_skin_sensitization	EC3	0.2	%	Mouse	Dermal	-	In Vivo; LLNAdb2013; LLNA	sheet=Data_invivo; excel_row=13555; Record_ID=skin_sensitization_invivo_3766; Data_Type=In Vivo; Internal_Data_Source=LLNAdb2013; Mixture=Chemical; DTXSID=DTXSID9021138; Assay=LLNA; Endpoint=EC3; Response=0.2; Response_Unit=%; Species=Mouse; Route=Dermal; Reference=Kimber et al. 1991; 1998208; 10.1016/0378-4274(91)90135-s; URL_CompTox=https://comptox.epa.gov/dashboard/chemical/details/DTXSID9021138
NTP_ICE_skin_sensitization	EC3	0.07	%	Mouse	Dermal	-	In Vivo; LLNAdb2013; LLNA	sheet=Data_invivo; excel_row=13559; Record_ID=skin_sensitization_invivo_3774; Data_Type=In Vivo; Internal_Data_Source=LLNAdb2013; Mixture=Chemical; DTXSID=DTXSID9021138; Assay=LLNA; Endpoint=EC3; Response=7.00E-02; Response_Unit=%; Species=Mouse; Route=Dermal; Reference=Warbrick et al. 1999; 10439339; 10.1002/(sici)1099-1263(199907/08)19:4<255::aid-jat573>3.0.co;2-s; URL_CompTox=https://comptox.epa.gov/dashboard/chemical/details/DTXSID9021138
NTP_ICE_skin_sensitization	EC3	0.13	%	Mouse	Dermal	-	In Vivo; LLNAdb2013; LLNA	sheet=Data_invivo; excel_row=13563; Record_ID=skin_sensitization_invivo_3778; Data_Type=In Vivo; Internal_Data_Source=LLNAdb2013; Mixture=Chemical; DTXSID=DTXSID9021138; Assay=LLNA; Endpoint=EC3; Response=0.13; Response_Unit=%; Species=Mouse; Route=Dermal; Reference=White et al. 2006; 17014438; 10.1111/j.1365-2222.2006.02561.x; URL_CompTox=https://comptox.epa.gov/dashboard/chemical/details/DTXSID9021138
NTP_ICE_skin_sensitization	EC3	0.15	%	Mouse	Dermal	-	In Vivo; LLNAdb2013; LLNA	sheet=Data_invivo; excel_row=13565; Record_ID=skin_sensitization_invivo_3780; Data_Type=In Vivo; Internal_Data_Source=LLNAdb2013; Mixture=Chemical; DTXSID=DTXSID9021138; Assay=LLNA; Endpoint=EC3; Response=0.15; Response_Unit=%; Species=Mouse; Route=Dermal; Reference=Warbrick et al. 1999; 10439339; 10.1002/(sici)1099-1263(199907/08)19:4<255::aid-jat573>3.0.co;2-s; URL_CompTox=https://comptox.epa.gov/dashboard/chemical/details/DTXSID9021138
NTP_ICE_skin_sensitization	EC3	0.05	%	Mouse	Dermal	-	In Vivo; LLNAdb2013; LLNA	sheet=Data_invivo; excel_row=13567; Record_ID=skin_sensitization_invivo_3782; Data_Type=In Vivo; Internal_Data_Source=LLNAdb2013; Mixture=Chemical; DTXSID=DTXSID9021138; Assay=LLNA; Endpoint=EC3; Response=0.05; Response_Unit=%; Species=Mouse; Route=Dermal; Reference=Montelius et al. 1994; Not available; Not available; URL_CompTox=https://comptox.epa.gov/dashboard/chemical/details/DTXSID9021138
NTP_ICE_skin_sensitization	EC3	0.1	%	Mouse	Dermal	-	In Vivo; LLNAdb2013; LLNA	sheet=Data_invivo; excel_row=13547; Record_ID=skin_sensitization_invivo_3755; Data_Type=In Vivo; Internal_Data_Source=LLNAdb2013; Mixture=Chemical; DTXSID=DTXSID9021138; Assay=LLNA; Endpoint=EC3; Response=0.1; Response_Unit=%; Species=Mouse; Route=Dermal; Reference=Gerberick et al. 2004; 15209809; 10.1111/j.0105-1873.2004.00290.x; URL_CompTox=https://comptox.epa.gov/dashboard/chemical/details/DTXSID9021138
NTP_ICE_skin_sensitization	EC3	2.2	%	Mouse	Dermal	-	In Vivo; LLNAdb2013; LLNA	sheet=Data_invivo; excel_row=13548; Record_ID=skin_sensitization_invivo_3757; Data_Type=In Vivo; Internal_Data_Source=LLNAdb2013; Mixture=Chemical; DTXSID=DTXSID9021138; Assay=LLNA; Endpoint=EC3; Response=2.2; Response_Unit=%; Species=Mouse; Route=Dermal; Reference=Kimber et al. 1991; 1998208; 10.1016/0378-4274(91)90135-s; URL_CompTox=https://comptox.epa.gov/dashboard/chemical/details/DTXSID9021138
NTP_ICE_skin_sensitization	EC3	0.4	%	Mouse	Dermal	-	In Vivo; LLNAdb2013; LLNA	sheet=Data_invivo; excel_row=13550; Record_ID=skin_sensitization_invivo_3759; Data_Type=In Vivo; Internal_Data_Source=LLNAdb2013; Mixture=Chemical; DTXSID=DTXSID9021138; Assay=LLNA; Endpoint=EC3; Response=0.4; Response_Unit=%; Species=Mouse; Route=Dermal; Reference=Kimber et al. 1991; 1998208; 10.1016/0378-4274(91)90135-s; URL_CompTox=https://comptox.epa.gov/dashboard/chemical/details/DTXSID9021138
NTP_ICE_skin_sensitization	EC3	0.001	%	Mouse	Dermal	-	In Vivo; LLNAdb2013; LLNA	sheet=Data_invivo; excel_row=13552; Record_ID=skin_sensitization_invivo_3761; Data_Type=In Vivo; Internal_Data_Source=LLNAdb2013; Mixture=Chemical; DTXSID=DTXSID9021138; Assay=LLNA; Endpoint=EC3; Response=1.00E-03; Response_Unit=%; Species=Mouse; Route=Dermal; Reference=Kimber et al. 1991; 1998208; 10.1016/0378-4274(91)90135-s; URL_CompTox=https://comptox.epa.gov/dashboard/chemical/details/DTXSID9021138
NTP_ICE_skin_sensitization	EC3	0.16	%	Mouse	Dermal	-	In Vivo; LLNAdb2013; LLNA	sheet=Data_invivo; excel_row=13554; Record_ID=skin_sensitization_invivo_3763; Data_Type=In Vivo; Internal_Data_Source=LLNAdb2013; Mixture=Chemical; DTXSID=DTXSID9021138; Assay=LLNA; Endpoint=EC3; Response=0.16; Response_Unit=%; Species=Mouse; Route=Dermal; Reference=Gerberick et al. 2005; 16536334; Not available; URL_CompTox=https://comptox.epa.gov/dashboard/chemical/details/DTXSID9021138
NTP_ICE_skin_sensitization	EC3	0.2	%	Mouse	Dermal	-	In Vivo; LLNAdb2013; LLNA	sheet=Data_invivo; excel_row=13555; Record_ID=skin_sensitization_invivo_3766; Data_Type=In Vivo; Internal_Data_Source=LLNAdb2013; Mixture=Chemical; DTXSID=DTXSID9021138; Assay=LLNA; Endpoint=EC3; Response=0.2; Response_Unit=%; Species=Mouse; Route=Dermal; Reference=Kimber et al. 1991; 1998208; 10.1016/0378-4274(91)90135-s; URL_CompTox=https://comptox.epa.gov/dashboard/chemical/details/DTXSID9021138
NTP_ICE_skin_sensitization	EC3	0.07	%	Mouse	Dermal	-	In Vivo; LLNAdb2013; LLNA	sheet=Data_invivo; excel_row=13559; Record_ID=skin_sensitization_invivo_3774; Data_Type=In Vivo; Internal_Data_Source=LLNAdb2013; Mixture=Chemical; DTXSID=DTXSID9021138; Assay=LLNA; Endpoint=EC3; Response=7.00E-02; Response_Unit=%; Species=Mouse; Route=Dermal; Reference=Warbrick et al. 1999; 10439339; 10.1002/(sici)1099-1263(199907/08)19:4<255::aid-jat573>3.0.co;2-s; URL_CompTox=https://comptox.epa.gov/dashboard/chemical/details/DTXSID9021138
NTP_ICE_skin_sensitization	EC3	0.13	%	Mouse	Dermal	-	In Vivo; LLNAdb2013; LLNA	sheet=Data_invivo; excel_row=13563; Record_ID=skin_sensitization_invivo_3778; Data_Type=In Vivo; Internal_Data_Source=LLNAdb2013; Mixture=Chemical; DTXSID=DTXSID9021138; Assay=LLNA; Endpoint=EC3; Response=0.13; Response_Unit=%; Species=Mouse; Route=Dermal; Reference=White et al. 2006; 17014438; 10.1111/j.1365-2222.2006.02561.x; URL_CompTox=https://comptox.epa.gov/dashboard/chemical/details/DTXSID9021138
NTP_ICE_skin_sensitization	EC3	0.15	%	Mouse	Dermal	-	In Vivo; LLNAdb2013; LLNA	sheet=Data_invivo; excel_row=13565; Record_ID=skin_sensitization_invivo_3780; Data_Type=In Vivo; Internal_Data_Source=LLNAdb2013; Mixture=Chemical; DTXSID=DTXSID9021138; Assay=LLNA; Endpoint=EC3; Response=0.15; Response_Unit=%; Species=Mouse; Route=Dermal; Reference=Warbrick et al. 1999; 10439339; 10.1002/(sici)1099-1263(199907/08)19:4<255::aid-jat573>3.0.co;2-s; URL_CompTox=https://comptox.epa.gov/dashboard/chemical/details/DTXSID9021138
NTP_ICE_skin_sensitization	EC3	0.05	%	Mouse	Dermal	-	In Vivo; LLNAdb2013; LLNA	sheet=Data_invivo; excel_row=13567; Record_ID=skin_sensitization_invivo_3782; Data_Type=In Vivo; Internal_Data_Source=LLNAdb2013; Mixture=Chemical; DTXSID=DTXSID9021138; Assay=LLNA; Endpoint=EC3; Response=0.05; Response_Unit=%; Species=Mouse; Route=Dermal; Reference=Montelius et al. 1994; Not available; Not available; URL_CompTox=https://comptox.epa.gov/dashboard/chemical/details/DTXSID9021138
NTP_ICE_skin_sensitization	EC3	0.1	%	Mouse	Dermal	-	In Vivo; LLNAdb2013; LLNA	sheet=Data_invivo; excel_row=13547; Record_ID=skin_sensitization_invivo_3755; Data_Type=In Vivo; Internal_Data_Source=LLNAdb2013; Mixture=Chemical; DTXSID=DTXSID9021138; Assay=LLNA; Endpoint=EC3; Response=0.1; Response_Unit=%; Species=Mouse; Route=Dermal; Reference=Gerberick et al. 2004; 15209809; 10.1111/j.0105-1873.2004.00290.x; URL_CompTox=https://comptox.epa.gov/dashboard/chemical/details/DTXSID9021138
NTP_ICE_skin_sensitization	EC3	2.2	%	Mouse	Dermal	-	In Vivo; LLNAdb2013; LLNA	sheet=Data_invivo; excel_row=13548; Record_ID=skin_sensitization_invivo_3757; Data_Type=In Vivo; Internal_Data_Source=LLNAdb2013; Mixture=Chemical; DTXSID=DTXSID9021138; Assay=LLNA; Endpoint=EC3; Response=2.2; Response_Unit=%; Species=Mouse; Route=Dermal; Reference=Kimber et al. 1991; 1998208; 10.1016/0378-4274(91)90135-s; URL_CompTox=https://comptox.epa.gov/dashboard/chemical/details/DTXSID9021138
NTP_ICE_skin_sensitization	EC3	0.4	%	Mouse	Dermal	-	In Vivo; LLNAdb2013; LLNA	sheet=Data_invivo; excel_row=13550; Record_ID=skin_sensitization_invivo_3759; Data_Type=In Vivo; Internal_Data_Source=LLNAdb2013; Mixture=Chemical; DTXSID=DTXSID9021138; Assay=LLNA; Endpoint=EC3; Response=0.4; Response_Unit=%; Species=Mouse; Route=Dermal; Reference=Kimber et al. 1991; 1998208; 10.1016/0378-4274(91)90135-s; URL_CompTox=https://comptox.epa.gov/dashboard/chemical/details/DTXSID9021138
NTP_ICE_skin_sensitization	EC3	0.001	%	Mouse	Dermal	-	In Vivo; LLNAdb2013; LLNA	sheet=Data_invivo; excel_row=13552; Record_ID=skin_sensitization_invivo_3761; Data_Type=In Vivo; Internal_Data_Source=LLNAdb2013; Mixture=Chemical; DTXSID=DTXSID9021138; Assay=LLNA; Endpoint=EC3; Response=1.00E-03; Response_Unit=%; Species=Mouse; Route=Dermal; Reference=Kimber et al. 1991; 1998208; 10.1016/0378-4274(91)90135-s; URL_CompTox=https://comptox.epa.gov/dashboard/chemical/details/DTXSID9021138
NTP_ICE_skin_sensitization	EC3	0.16	%	Mouse	Dermal	-	In Vivo; LLNAdb2013; LLNA	sheet=Data_invivo; excel_row=13554; Record_ID=skin_sensitization_invivo_3763; Data_Type=In Vivo; Internal_Data_Source=LLNAdb2013; Mixture=Chemical; DTXSID=DTXSID9021138; Assay=LLNA; Endpoint=EC3; Response=0.16; Response_Unit=%; Species=Mouse; Route=Dermal; Reference=Gerberick et al. 2005; 16536334; Not available; URL_CompTox=https://comptox.epa.gov/dashboard/chemical/details/DTXSID9021138
NTP_ICE_skin_sensitization	EC3	0.2	%	Mouse	Dermal	-	In Vivo; LLNAdb2013; LLNA	sheet=Data_invivo; excel_row=13555; Record_ID=skin_sensitization_invivo_3766; Data_Type=In Vivo; Internal_Data_Source=LLNAdb2013; Mixture=Chemical; DTXSID=DTXSID9021138; Assay=LLNA; Endpoint=EC3; Response=0.2; Response_Unit=%; Species=Mouse; Route=Dermal; Reference=Kimber et al. 1991; 1998208; 10.1016/0378-4274(91)90135-s; URL_CompTox=https://comptox.epa.gov/dashboard/chemical/details/DTXSID9021138
NTP_ICE_skin_sensitization	EC3	0.07	%	Mouse	Dermal	-	In Vivo; LLNAdb2013; LLNA	sheet=Data_invivo; excel_row=13559; Record_ID=skin_sensitization_invivo_3774; Data_Type=In Vivo; Internal_Data_Source=LLNAdb2013; Mixture=Chemical; DTXSID=DTXSID9021138; Assay=LLNA; Endpoint=EC3; Response=7.00E-02; Response_Unit=%; Species=Mouse; Route=Dermal; Reference=Warbrick et al. 1999; 10439339; 10.1002/(sici)1099-1263(199907/08)19:4<255::aid-jat573>3.0.co;2-s; URL_CompTox=https://comptox.epa.gov/dashboard/chemical/details/DTXSID9021138
NTP_ICE_skin_sensitization	EC3	0.13	%	Mouse	Dermal	-	In Vivo; LLNAdb2013; LLNA	sheet=Data_invivo; excel_row=13563; Record_ID=skin_sensitization_invivo_3778; Data_Type=In Vivo; Internal_Data_Source=LLNAdb2013; Mixture=Chemical; DTXSID=DTXSID9021138; Assay=LLNA; Endpoint=EC3; Response=0.13; Response_Unit=%; Species=Mouse; Route=Dermal; Reference=White et al. 2006; 17014438; 10.1111/j.1365-2222.2006.02561.x; URL_CompTox=https://comptox.epa.gov/dashboard/chemical/details/DTXSID9021138
NTP_ICE_skin_sensitization	EC3	0.15	%	Mouse	Dermal	-	In Vivo; LLNAdb2013; LLNA	sheet=Data_invivo; excel_row=13565; Record_ID=skin_sensitization_invivo_3780; Data_Type=In Vivo; Internal_Data_Source=LLNAdb2013; Mixture=Chemical; DTXSID=DTXSID9021138; Assay=LLNA; Endpoint=EC3; Response=0.15; Response_Unit=%; Species=Mouse; Route=Dermal; Reference=Warbrick et al. 1999; 10439339; 10.1002/(sici)1099-1263(199907/08)19:4<255::aid-jat573>3.0.co;2-s; URL_CompTox=https://comptox.epa.gov/dashboard/chemical/details/DTXSID9021138
NTP_ICE_skin_sensitization	EC3	0.05	%	Mouse	Dermal	-	In Vivo; LLNAdb2013; LLNA	sheet=Data_invivo; excel_row=13567; Record_ID=skin_sensitization_invivo_3782; Data_Type=In Vivo; Internal_Data_Source=LLNAdb2013; Mixture=Chemical; DTXSID=DTXSID9021138; Assay=LLNA; Endpoint=EC3; Response=0.05; Response_Unit=%; Species=Mouse; Route=Dermal; Reference=Montelius et al. 1994; Not available; Not available; URL_CompTox=https://comptox.epa.gov/dashboard/chemical/details/DTXSID9021138
NTP_ICE_skin_sensitization	IC50	399.98	uM	-	Dermal	-	In Vitro; KeratinoSens2015; KeratinoSens	sheet=Data_invitro; excel_row=4391; Record_ID=skin_sensitization_invitro_992; Data_Type=In Vitro; Internal_Data_Source=KeratinoSens2015; Mixture=Chemical; DTXSID=DTXSID9021138; Assay=KeratinoSens; Endpoint=IC50; Reported_Response=399.98; Reported_Response_Unit=uM; Response=399.98; Response_Unit=uM; Reference=Joint Research Centre of the European Union 2014; URL_CompTox=https://comptox.epa.gov/dashboard/chemical/details/DTXSID9021138
NTP_ICE_skin_sensitization	IC50	400.7	uM	-	Dermal	-	In Vitro; KeratinoSens2015; KeratinoSens	sheet=Data_invitro; excel_row=4392; Record_ID=skin_sensitization_invitro_1020; Data_Type=In Vitro; Internal_Data_Source=KeratinoSens2015; Mixture=Chemical; DTXSID=DTXSID9021138; Assay=KeratinoSens; Endpoint=IC50; Reported_Response=400.7; Reported_Response_Unit=uM; Response=400.7; Response_Unit=uM; Reference=Natsch et al. 2011; 22023385; 10.1021/tx2003678; URL_CompTox=https://comptox.epa.gov/dashboard/chemical/details/DTXSID9021138
NTP_ICE_skin_sensitization	IC50	422.93	uM	-	Dermal	-	In Vitro; KeratinoSens2015; KeratinoSens	sheet=Data_invitro; excel_row=4393; Record_ID=skin_sensitization_invitro_995; Data_Type=In Vitro; Internal_Data_Source=KeratinoSens2015; Mixture=Chemical; DTXSID=DTXSID9021138; Assay=KeratinoSens; Endpoint=IC50; Reported_Response=422.93; Reported_Response_Unit=uM; Response=422.93; Response_Unit=uM; Reference=Joint Research Centre of the European Union 2014; URL_CompTox=https://comptox.epa.gov/dashboard/chemical/details/DTXSID9021138
NTP_ICE_skin_sensitization	IC50	427	uM	-	Dermal	-	In Vitro; KeratinoSens2015; KeratinoSens	sheet=Data_invitro; excel_row=4394; Record_ID=skin_sensitization_invitro_1010; Data_Type=In Vitro; Internal_Data_Source=KeratinoSens2015; Mixture=Chemical; DTXSID=DTXSID9021138; Assay=KeratinoSens; Endpoint=IC50; Reported_Response=427; Reported_Response_Unit=uM; Response=427; Response_Unit=uM; Reference=Natsch et al. 2011; 22023385; 10.1021/tx2003678; URL_CompTox=https://comptox.epa.gov/dashboard/chemical/details/DTXSID9021138
NTP_ICE_skin_sensitization	IC50	438.95	uM	-	Dermal	-	In Vitro; CE_KeratinoSense2018; KeratinoSens	sheet=Data_invitro; excel_row=4395; Record_ID=skin_sensitization_invitro_1017; Data_Type=In Vitro; Internal_Data_Source=CE_KeratinoSense2018; Mixture=Chemical; DTXSID=DTXSID9021138; Assay=KeratinoSens; Endpoint=IC50; Reported_Response=438.95; Reported_Response_Unit=uM; Response=438.95; Response_Unit=uM; Reference=Emter et al. 2010; 20307559; 10.1016/j.taap.2010.03.009\|Natsch et al. 2013; 23576290; 10.1002/jat.2868\|Urbisch et al. 2015; 25541156; 10.1016/j.yrtph.2014.12.008; URL_CompTox=https://comptox.epa.gov/dashboard/chemical/details/DTXSID9021138
NTP_ICE_skin_sensitization	IC50	447.39	uM	-	Dermal	-	In Vitro; KeratinoSens2015; KeratinoSens	sheet=Data_invitro; excel_row=4396; Record_ID=skin_sensitization_invitro_1000; Data_Type=In Vitro; Internal_Data_Source=KeratinoSens2015; Mixture=Chemical; DTXSID=DTXSID9021138; Assay=KeratinoSens; Endpoint=IC50; Reported_Response=447.39; Reported_Response_Unit=uM; Response=447.39; Response_Unit=uM; Reference=Joint Research Centre of the European Union 2014; URL_CompTox=https://comptox.epa.gov/dashboard/chemical/details/DTXSID9021138
NTP_ICE_skin_sensitization	IC50	464.55	uM	-	Dermal	-	In Vitro; KeratinoSens2015; KeratinoSens	sheet=Data_invitro; excel_row=4397; Record_ID=skin_sensitization_invitro_1004; Data_Type=In Vitro; Internal_Data_Source=KeratinoSens2015; Mixture=Chemical; DTXSID=DTXSID9021138; Assay=KeratinoSens; Endpoint=IC50; Reported_Response=464.55; Reported_Response_Unit=uM; Response=464.55; Response_Unit=uM; Reference=Joint Research Centre of the European Union 2014; URL_CompTox=https://comptox.epa.gov/dashboard/chemical/details/DTXSID9021138
NTP_ICE_skin_sensitization	IC50	577.2	uM	-	Dermal	-	In Vitro; KeratinoSens2015; KeratinoSens	sheet=Data_invitro; excel_row=4398; Record_ID=skin_sensitization_invitro_1008; Data_Type=In Vitro; Internal_Data_Source=KeratinoSens2015; Mixture=Chemical; DTXSID=DTXSID9021138; Assay=KeratinoSens; Endpoint=IC50; Reported_Response=577.20000000000005; Reported_Response_Unit=uM; Response=577.2; Response_Unit=uM; Reference=Natsch et al. 2011; 22023385; 10.1021/tx2003678; URL_CompTox=https://comptox.epa.gov/dashboard/chemical/details/DTXSID9021138
NTP_ICE_skin_sensitization	IC50	648.9	uM	-	Dermal	-	In Vitro; KeratinoSens2015; KeratinoSens	sheet=Data_invitro; excel_row=4399; Record_ID=skin_sensitization_invitro_1009; Data_Type=In Vitro; Internal_Data_Source=KeratinoSens2015; Mixture=Chemical; DTXSID=DTXSID9021138; Assay=KeratinoSens; Endpoint=IC50; Reported_Response=648.9; Reported_Response_Unit=uM; Response=648.9; Response_Unit=uM; Reference=Natsch et al. 2011; 22023385; 10.1021/tx2003678; URL_CompTox=https://comptox.epa.gov/dashboard/chemical/details/DTXSID9021138
NTP_ICE_skin_sensitization	IC50	662.35	uM	-	Dermal	-	In Vitro; KeratinoSens2015; KeratinoSens	sheet=Data_invitro; excel_row=4400; Record_ID=skin_sensitization_invitro_998; Data_Type=In Vitro; Internal_Data_Source=KeratinoSens2015; Mixture=Chemical; DTXSID=DTXSID9021138; Assay=KeratinoSens; Endpoint=IC50; Reported_Response=662.35; Reported_Response_Unit=uM; Response=662.35; Response_Unit=uM; Reference=Joint Research Centre of the European Union 2014; URL_CompTox=https://comptox.epa.gov/dashboard/chemical/details/DTXSID9021138
NTP_ICE_skin_sensitization	IC50	704.25	uM	-	Dermal	-	In Vitro; KeratinoSens2015; KeratinoSens	sheet=Data_invitro; excel_row=4402; Record_ID=skin_sensitization_invitro_1001; Data_Type=In Vitro; Internal_Data_Source=KeratinoSens2015; Mixture=Chemical; DTXSID=DTXSID9021138; Assay=KeratinoSens; Endpoint=IC50; Reported_Response=704.25; Reported_Response_Unit=uM; Response=704.25; Response_Unit=uM; Reference=Joint Research Centre of the European Union 2014; URL_CompTox=https://comptox.epa.gov/dashboard/chemical/details/DTXSID9021138
NTP_ICE_skin_sensitization	IC50	736.41	uM	-	Dermal	-	In Vitro; KeratinoSens2015; KeratinoSens	sheet=Data_invitro; excel_row=4403; Record_ID=skin_sensitization_invitro_997; Data_Type=In Vitro; Internal_Data_Source=KeratinoSens2015; Mixture=Chemical; DTXSID=DTXSID9021138; Assay=KeratinoSens; Endpoint=IC50; Reported_Response=736.41; Reported_Response_Unit=uM; Response=736.41; Response_Unit=uM; Reference=Joint Research Centre of the European Union 2014; URL_CompTox=https://comptox.epa.gov/dashboard/chemical/details/DTXSID9021138
NTP_ICE_skin_sensitization	IC50	867.33	uM	-	Dermal	-	In Vitro; KeratinoSens2015; KeratinoSens	sheet=Data_invitro; excel_row=4405; Record_ID=skin_sensitization_invitro_1002; Data_Type=In Vitro; Internal_Data_Source=KeratinoSens2015; Mixture=Chemical; DTXSID=DTXSID9021138; Assay=KeratinoSens; Endpoint=IC50; Reported_Response=867.33; Reported_Response_Unit=uM; Response=867.33; Response_Unit=uM; Reference=Joint Research Centre of the European Union 2014; URL_CompTox=https://comptox.epa.gov/dashboard/chemical/details/DTXSID9021138
NTP_ICE_skin_sensitization	IC50	872.11	uM	-	Dermal	-	In Vitro; KeratinoSens2015; KeratinoSens	sheet=Data_invitro; excel_row=4406; Record_ID=skin_sensitization_invitro_1005; Data_Type=In Vitro; Internal_Data_Source=KeratinoSens2015; Mixture=Chemical; DTXSID=DTXSID9021138; Assay=KeratinoSens; Endpoint=IC50; Reported_Response=872.11; Reported_Response_Unit=uM; Response=872.11; Response_Unit=uM; Reference=Joint Research Centre of the European Union 2014; URL_CompTox=https://comptox.epa.gov/dashboard/chemical/details/DTXSID9021138
NTP_ICE_skin_sensitization	IC50	192.22	uM	-	Dermal	-	In Vitro; KeratinoSens2015; KeratinoSens	sheet=Data_invitro; excel_row=4459; Record_ID=skin_sensitization_invitro_1003; Data_Type=In Vitro; Internal_Data_Source=KeratinoSens2015; Mixture=Chemical; DTXSID=DTXSID9021138; Assay=KeratinoSens; Endpoint=IC50; Reported_Response=192.22; Reported_Response_Unit=uM; Response=192.22; Response_Unit=uM; Reference=Joint Research Centre of the European Union 2014; URL_CompTox=https://comptox.epa.gov/dashboard/chemical/details/DTXSID9021138
NTP_ICE_skin_sensitization	IC50	302	uM	-	Dermal	-	In Vitro; KeratinoSens2015; KeratinoSens	sheet=Data_invitro; excel_row=4460; Record_ID=skin_sensitization_invitro_1016; Data_Type=In Vitro; Internal_Data_Source=KeratinoSens2015; Mixture=Chemical; DTXSID=DTXSID9021138; Assay=KeratinoSens; Endpoint=IC50; Reported_Response=302; Reported_Response_Unit=uM; Response=302; Response_Unit=uM; Reference=Bauch et al. 2011; 21669280; 10.1016/j.tiv.2011.05.030\|Bauch et al. 2012; 22659254; 10.1016/j.yrtph.2012.05.013; URL_CompTox=https://comptox.epa.gov/dashboard/chemical/details/DTXSID9021138
NTP_ICE_skin_sensitization	IC50	380.32	uM	-	Dermal	-	In Vitro; KeratinoSens2015; KeratinoSens	sheet=Data_invitro; excel_row=4461; Record_ID=skin_sensitization_invitro_993; Data_Type=In Vitro; Internal_Data_Source=KeratinoSens2015; Mixture=Chemical; DTXSID=DTXSID9021138; Assay=KeratinoSens; Endpoint=IC50; Reported_Response=380.32; Reported_Response_Unit=uM; Response=380.32; Response_Unit=uM; Reference=Joint Research Centre of the European Union 2014; URL_CompTox=https://comptox.epa.gov/dashboard/chemical/details/DTXSID9021138
NTP_ICE_skin_sensitization	IC50	392.86	uM	-	Dermal	-	In Vitro; KeratinoSens2015; KeratinoSens	sheet=Data_invitro; excel_row=4462; Record_ID=skin_sensitization_invitro_994; Data_Type=In Vitro; Internal_Data_Source=KeratinoSens2015; Mixture=Chemical; DTXSID=DTXSID9021138; Assay=KeratinoSens; Endpoint=IC50; Reported_Response=392.86; Reported_Response_Unit=uM; Response=392.86; Response_Unit=uM; Reference=Joint Research Centre of the European Union 2014; URL_CompTox=https://comptox.epa.gov/dashboard/chemical/details/DTXSID9021138
NTP_ICE_skin_sensitization	IC50	394.21	uM	-	Dermal	-	In Vitro; KeratinoSens2015; KeratinoSens	sheet=Data_invitro; excel_row=4463; Record_ID=skin_sensitization_invitro_999; Data_Type=In Vitro; Internal_Data_Source=KeratinoSens2015; Mixture=Chemical; DTXSID=DTXSID9021138; Assay=KeratinoSens; Endpoint=IC50; Reported_Response=394.21; Reported_Response_Unit=uM; Response=394.21; Response_Unit=uM; Reference=Joint Research Centre of the European Union 2014; URL_CompTox=https://comptox.epa.gov/dashboard/chemical/details/DTXSID9021138
NTP_ICE_skin_sensitization	IC50	396.4	uM	-	Dermal	-	In Vitro; KeratinoSens2015; KeratinoSens	sheet=Data_invitro; excel_row=4464; Record_ID=skin_sensitization_invitro_1011; Data_Type=In Vitro; Internal_Data_Source=KeratinoSens2015; Mixture=Chemical; DTXSID=DTXSID9021138; Assay=KeratinoSens; Endpoint=IC50; Reported_Response=396.4; Reported_Response_Unit=uM; Response=396.4; Response_Unit=uM; Reference=Natsch et al. 2011; 22023385; 10.1021/tx2003678; URL_CompTox=https://comptox.epa.gov/dashboard/chemical/details/DTXSID9021138
NTP_ICE_skin_sensitization	IC50	397.28	uM	-	Dermal	-	In Vitro; KeratinoSens2015; KeratinoSens	sheet=Data_invitro; excel_row=4465; Record_ID=skin_sensitization_invitro_1006; Data_Type=In Vitro; Internal_Data_Source=KeratinoSens2015; Mixture=Chemical; DTXSID=DTXSID9021138; Assay=KeratinoSens; Endpoint=IC50; Reported_Response=397.28; Reported_Response_Unit=uM; Response=397.28; Response_Unit=uM; Reference=Joint Research Centre of the European Union 2014; URL_CompTox=https://comptox.epa.gov/dashboard/chemical/details/DTXSID9021138
NTP_ICE_skin_sensitization	IC50	399.12	uM	-	Dermal	-	In Vitro; KeratinoSens2015; KeratinoSens	sheet=Data_invitro; excel_row=4466; Record_ID=skin_sensitization_invitro_996; Data_Type=In Vitro; Internal_Data_Source=KeratinoSens2015; Mixture=Chemical; DTXSID=DTXSID9021138; Assay=KeratinoSens; Endpoint=IC50; Reported_Response=399.12; Reported_Response_Unit=uM; Response=399.12; Response_Unit=uM; Reference=Joint Research Centre of the European Union 2014; URL_CompTox=https://comptox.epa.gov/dashboard/chemical/details/DTXSID9021138
NTP_ICE_skin_sensitization	IC50	>132	uM	-	Dermal	-	In Vitro; Urbisch_SkinSensitization2020; LuSens	sheet=Data_invitro; excel_row=7682; Record_ID=skin_sensitization_invitro_1855; Data_Type=In Vitro; Internal_Data_Source=Urbisch_SkinSensitization2020; Mixture=Chemical; DTXSID=DTXSID9021138; Assay=LuSens; Endpoint=IC50; Response_Modifier=>; Reported_Response_Modifier=>; Reported_Response=132; Reported_Response_Unit=uM; Response=132; Response_Unit=uM; Reference=Urbisch et al. 2015; 25541156; 10.1016/j.yrtph.2014.12.008; URL_CompTox=https://comptox.epa.gov/dashboard/chemical/details/DTXSID9021138
NTP_ICE_skin_sensitization	Imax	11.73	ratio	-	Dermal	-	In Vitro; KeratinoSens2015; KeratinoSens	sheet=Data_invitro; excel_row=4408; Record_ID=skin_sensitization_invitro_994; Data_Type=In Vitro; Internal_Data_Source=KeratinoSens2015; Mixture=Chemical; DTXSID=DTXSID9021138; Assay=KeratinoSens; Endpoint=Imax; Reported_Response=11.733000000000001; Reported_Response_Unit=Unitless; Response=11.73; Response_Unit=Ratio; Reference=Joint Research Centre of the European Union 2014; URL_CompTox=https://comptox.epa.gov/dashboard/chemical/details/DTXSID9021138
NTP_ICE_skin_sensitization	Imax	12.589	ratio	-	Dermal	-	In Vitro; KeratinoSens2015; KeratinoSens	sheet=Data_invitro; excel_row=4409; Record_ID=skin_sensitization_invitro_1003; Data_Type=In Vitro; Internal_Data_Source=KeratinoSens2015; Mixture=Chemical; DTXSID=DTXSID9021138; Assay=KeratinoSens; Endpoint=Imax; Reported_Response=12.589; Reported_Response_Unit=Unitless; Response=12.589; Response_Unit=Ratio; Reference=Joint Research Centre of the European Union 2014; URL_CompTox=https://comptox.epa.gov/dashboard/chemical/details/DTXSID9021138
NTP_ICE_skin_sensitization	Imax	131.7	ratio	-	Dermal	-	In Vitro; KeratinoSens2015; KeratinoSens	sheet=Data_invitro; excel_row=4410; Record_ID=skin_sensitization_invitro_1016; Data_Type=In Vitro; Internal_Data_Source=KeratinoSens2015; Mixture=Chemical; DTXSID=DTXSID9021138; Assay=KeratinoSens; Endpoint=Imax; Reported_Response=131.69999999999999; Reported_Response_Unit=Unitless; Response=131.7; Response_Unit=Ratio; Reference=Bauch et al. 2011; 21669280; 10.1016/j.tiv.2011.05.030\|Bauch et al. 2012; 22659254; 10.1016/j.yrtph.2012.05.013; URL_CompTox=https://comptox.epa.gov/dashboard/chemical/details/DTXSID9021138
NTP_ICE_skin_sensitization	Imax	16.459	ratio	-	Dermal	-	In Vitro; KeratinoSens2015; KeratinoSens	sheet=Data_invitro; excel_row=4411; Record_ID=skin_sensitization_invitro_997; Data_Type=In Vitro; Internal_Data_Source=KeratinoSens2015; Mixture=Chemical; DTXSID=DTXSID9021138; Assay=KeratinoSens; Endpoint=Imax; Reported_Response=16.459; Reported_Response_Unit=Unitless; Response=16.459; Response_Unit=Ratio; Reference=Joint Research Centre of the European Union 2014; URL_CompTox=https://comptox.epa.gov/dashboard/chemical/details/DTXSID9021138
NTP_ICE_skin_sensitization	Imax	17.77	ratio	-	Dermal	-	In Vitro; KeratinoSens2015; KeratinoSens	sheet=Data_invitro; excel_row=4412; Record_ID=skin_sensitization_invitro_1005; Data_Type=In Vitro; Internal_Data_Source=KeratinoSens2015; Mixture=Chemical; DTXSID=DTXSID9021138; Assay=KeratinoSens; Endpoint=Imax; Reported_Response=17.774000000000001; Reported_Response_Unit=Unitless; Response=17.77; Response_Unit=Ratio; Reference=Joint Research Centre of the European Union 2014; URL_CompTox=https://comptox.epa.gov/dashboard/chemical/details/DTXSID9021138
NTP_ICE_skin_sensitization	Imax	19.02	ratio	-	Dermal	-	In Vitro; KeratinoSens2015; KeratinoSens	sheet=Data_invitro; excel_row=4413; Record_ID=skin_sensitization_invitro_998; Data_Type=In Vitro; Internal_Data_Source=KeratinoSens2015; Mixture=Chemical; DTXSID=DTXSID9021138; Assay=KeratinoSens; Endpoint=Imax; Reported_Response=19.021999999999998; Reported_Response_Unit=Unitless; Response=19.02; Response_Unit=Ratio; Reference=Joint Research Centre of the European Union 2014; URL_CompTox=https://comptox.epa.gov/dashboard/chemical/details/DTXSID9021138
NTP_ICE_skin_sensitization	Imax	19.4	ratio	-	Dermal	-	In Vitro; KeratinoSens2015; KeratinoSens	sheet=Data_invitro; excel_row=4414; Record_ID=skin_sensitization_invitro_1008; Data_Type=In Vitro; Internal_Data_Source=KeratinoSens2015; Mixture=Chemical; DTXSID=DTXSID9021138; Assay=KeratinoSens; Endpoint=Imax; Reported_Response=19.399999999999999; Reported_Response_Unit=Unitless; Response=19.4; Response_Unit=Ratio; Reference=Natsch et al. 2011; 22023385; 10.1021/tx2003678; URL_CompTox=https://comptox.epa.gov/dashboard/chemical/details/DTXSID9021138
NTP_ICE_skin_sensitization	Imax	20	ratio	-	Dermal	-	In Vitro; KeratinoSens2015; KeratinoSens	sheet=Data_invitro; excel_row=4415; Record_ID=skin_sensitization_invitro_1010; Data_Type=In Vitro; Internal_Data_Source=KeratinoSens2015; Mixture=Chemical; DTXSID=DTXSID9021138; Assay=KeratinoSens; Endpoint=Imax; Reported_Response=20; Reported_Response_Unit=Unitless; Response=20; Response_Unit=Ratio; Reference=Natsch et al. 2011; 22023385; 10.1021/tx2003678; URL_CompTox=https://comptox.epa.gov/dashboard/chemical/details/DTXSID9021138
NTP_ICE_skin_sensitization	Imax	22.21	ratio	-	Dermal	-	In Vitro; KeratinoSens2015; KeratinoSens	sheet=Data_invitro; excel_row=4416; Record_ID=skin_sensitization_invitro_992; Data_Type=In Vitro; Internal_Data_Source=KeratinoSens2015; Mixture=Chemical; DTXSID=DTXSID9021138; Assay=KeratinoSens; Endpoint=Imax; Reported_Response=22.21; Reported_Response_Unit=Unitless; Response=22.21; Response_Unit=Ratio; Reference=Joint Research Centre of the European Union 2014; URL_CompTox=https://comptox.epa.gov/dashboard/chemical/details/DTXSID9021138
NTP_ICE_skin_sensitization	Imax	22.61	ratio	-	Dermal	-	In Vitro; KeratinoSens2015; KeratinoSens	sheet=Data_invitro; excel_row=4417; Record_ID=skin_sensitization_invitro_996; Data_Type=In Vitro; Internal_Data_Source=KeratinoSens2015; Mixture=Chemical; DTXSID=DTXSID9021138; Assay=KeratinoSens; Endpoint=Imax; Reported_Response=22.611999999999998; Reported_Response_Unit=Unitless; Response=22.61; Response_Unit=Ratio; Reference=Joint Research Centre of the European Union 2014; URL_CompTox=https://comptox.epa.gov/dashboard/chemical/details/DTXSID9021138
NTP_ICE_skin_sensitization	Imax	22.66	ratio	-	Dermal	-	In Vitro; KeratinoSens2015; KeratinoSens	sheet=Data_invitro; excel_row=4418; Record_ID=skin_sensitization_invitro_999; Data_Type=In Vitro; Internal_Data_Source=KeratinoSens2015; Mixture=Chemical; DTXSID=DTXSID9021138; Assay=KeratinoSens; Endpoint=Imax; Reported_Response=22.655999999999999; Reported_Response_Unit=Unitless; Response=22.66; Response_Unit=Ratio; Reference=Joint Research Centre of the European Union 2014; URL_CompTox=https://comptox.epa.gov/dashboard/chemical/details/DTXSID9021138
NTP_ICE_skin_sensitization	Imax	23.2	ratio	-	Dermal	-	In Vitro; KeratinoSens2015; KeratinoSens	sheet=Data_invitro; excel_row=4419; Record_ID=skin_sensitization_invitro_1011; Data_Type=In Vitro; Internal_Data_Source=KeratinoSens2015; Mixture=Chemical; DTXSID=DTXSID9021138; Assay=KeratinoSens; Endpoint=Imax; Reported_Response=23.2; Reported_Response_Unit=Unitless; Response=23.2; Response_Unit=Ratio; Reference=Natsch et al. 2011; 22023385; 10.1021/tx2003678; URL_CompTox=https://comptox.epa.gov/dashboard/chemical/details/DTXSID9021138
NTP_ICE_skin_sensitization	Imax	25.06	ratio	-	Dermal	-	In Vitro; KeratinoSens2015; KeratinoSens	sheet=Data_invitro; excel_row=4420; Record_ID=skin_sensitization_invitro_1019; Data_Type=In Vitro; Internal_Data_Source=KeratinoSens2015; Mixture=Chemical; DTXSID=DTXSID9021138; Assay=KeratinoSens; Endpoint=Imax; Reported_Response=25.06; Reported_Response_Unit=Unitless; Response=25.06; Response_Unit=Ratio; Reference=Joint Research Centre of the European Union 2014; URL_CompTox=https://comptox.epa.gov/dashboard/chemical/details/DTXSID9021138
NTP_ICE_skin_sensitization	Imax	26.8	ratio	-	Dermal	-	In Vitro; CE_KeratinoSense2018; KeratinoSens	sheet=Data_invitro; excel_row=4421; Record_ID=skin_sensitization_invitro_1017; Data_Type=In Vitro; Internal_Data_Source=CE_KeratinoSense2018; Mixture=Chemical; DTXSID=DTXSID9021138; Assay=KeratinoSens; Endpoint=Imax; Reported_Response=26.8; Reported_Response_Unit=Unitless; Response=26.8; Response_Unit=Ratio; Reference=Emter et al. 2010; 20307559; 10.1016/j.taap.2010.03.009\|Natsch et al. 2013; 23576290; 10.1002/jat.2868\|Urbisch et al. 2015; 25541156; 10.1016/j.yrtph.2014.12.008; URL_CompTox=https://comptox.epa.gov/dashboard/chemical/details/DTXSID9021138
NTP_ICE_skin_sensitization	Imax	28.55	ratio	-	Dermal	-	In Vitro; KeratinoSens2015; KeratinoSens	sheet=Data_invitro; excel_row=4422; Record_ID=skin_sensitization_invitro_1014; Data_Type=In Vitro; Internal_Data_Source=KeratinoSens2015; Mixture=Chemical; DTXSID=DTXSID9021138; Assay=KeratinoSens; Endpoint=Imax; Reported_Response=28.547000000000001; Reported_Response_Unit=Unitless; Response=28.55; Response_Unit=Ratio; Reference=Joint Research Centre of the European Union 2014; URL_CompTox=https://comptox.epa.gov/dashboard/chemical/details/DTXSID9021138
NTP_ICE_skin_sensitization	Imax	29.558	ratio	-	Dermal	-	In Vitro; KeratinoSens2015; KeratinoSens	sheet=Data_invitro; excel_row=4423; Record_ID=skin_sensitization_invitro_1004; Data_Type=In Vitro; Internal_Data_Source=KeratinoSens2015; Mixture=Chemical; DTXSID=DTXSID9021138; Assay=KeratinoSens; Endpoint=Imax; Reported_Response=29.558; Reported_Response_Unit=Unitless; Response=29.558; Response_Unit=Ratio; Reference=Joint Research Centre of the European Union 2014; URL_CompTox=https://comptox.epa.gov/dashboard/chemical/details/DTXSID9021138
NTP_ICE_skin_sensitization	Imax	31.494	ratio	-	Dermal	-	In Vitro; KeratinoSens2015; KeratinoSens	sheet=Data_invitro; excel_row=4424; Record_ID=skin_sensitization_invitro_1001; Data_Type=In Vitro; Internal_Data_Source=KeratinoSens2015; Mixture=Chemical; DTXSID=DTXSID9021138; Assay=KeratinoSens; Endpoint=Imax; Reported_Response=31.494; Reported_Response_Unit=Unitless; Response=31.494; Response_Unit=Ratio; Reference=Joint Research Centre of the European Union 2014; URL_CompTox=https://comptox.epa.gov/dashboard/chemical/details/DTXSID9021138
NTP_ICE_skin_sensitization	Imax	32.61	ratio	-	Dermal	-	In Vitro; KeratinoSens2015; KeratinoSens	sheet=Data_invitro; excel_row=4425; Record_ID=skin_sensitization_invitro_1002; Data_Type=In Vitro; Internal_Data_Source=KeratinoSens2015; Mixture=Chemical; DTXSID=DTXSID9021138; Assay=KeratinoSens; Endpoint=Imax; Reported_Response=32.612000000000002; Reported_Response_Unit=Unitless; Response=32.61; Response_Unit=Ratio; Reference=Joint Research Centre of the European Union 2014; URL_CompTox=https://comptox.epa.gov/dashboard/chemical/details/DTXSID9021138
NTP_ICE_skin_sensitization	Imax	35.23	ratio	-	Dermal	-	In Vitro; KeratinoSens2015; KeratinoSens	sheet=Data_invitro; excel_row=4426; Record_ID=skin_sensitization_invitro_1006; Data_Type=In Vitro; Internal_Data_Source=KeratinoSens2015; Mixture=Chemical; DTXSID=DTXSID9021138; Assay=KeratinoSens; Endpoint=Imax; Reported_Response=35.229999999999997; Reported_Response_Unit=Unitless; Response=35.23; Response_Unit=Ratio; Reference=Joint Research Centre of the European Union 2014; URL_CompTox=https://comptox.epa.gov/dashboard/chemical/details/DTXSID9021138
NTP_ICE_skin_sensitization	Imax	37.28	ratio	-	Dermal	-	In Vitro; KeratinoSens2015; KeratinoSens	sheet=Data_invitro; excel_row=4427; Record_ID=skin_sensitization_invitro_993; Data_Type=In Vitro; Internal_Data_Source=KeratinoSens2015; Mixture=Chemical; DTXSID=DTXSID9021138; Assay=KeratinoSens; Endpoint=Imax; Reported_Response=37.277000000000001; Reported_Response_Unit=Unitless; Response=37.28; Response_Unit=Ratio; Reference=Joint Research Centre of the European Union 2014; URL_CompTox=https://comptox.epa.gov/dashboard/chemical/details/DTXSID9021138
NTP_ICE_skin_sensitization	Imax	39	ratio	-	Dermal	-	In Vitro; KeratinoSens2015; KeratinoSens	sheet=Data_invitro; excel_row=4428; Record_ID=skin_sensitization_invitro_1009; Data_Type=In Vitro; Internal_Data_Source=KeratinoSens2015; Mixture=Chemical; DTXSID=DTXSID9021138; Assay=KeratinoSens; Endpoint=Imax; Reported_Response=39; Reported_Response_Unit=Unitless; Response=39; Response_Unit=Ratio; Reference=Natsch et al. 2011; 22023385; 10.1021/tx2003678; URL_CompTox=https://comptox.epa.gov/dashboard/chemical/details/DTXSID9021138
NTP_ICE_skin_sensitization	Imax	45.2	ratio	-	Dermal	-	In Vitro; KeratinoSens2015; KeratinoSens	sheet=Data_invitro; excel_row=4429; Record_ID=skin_sensitization_invitro_1020; Data_Type=In Vitro; Internal_Data_Source=KeratinoSens2015; Mixture=Chemical; DTXSID=DTXSID9021138; Assay=KeratinoSens; Endpoint=Imax; Reported_Response=45.2; Reported_Response_Unit=Unitless; Response=45.2; Response_Unit=Ratio; Reference=Natsch et al. 2011; 22023385; 10.1021/tx2003678; URL_CompTox=https://comptox.epa.gov/dashboard/chemical/details/DTXSID9021138
NTP_ICE_skin_sensitization	Imax	52.887	ratio	-	Dermal	-	In Vitro; KeratinoSens2015; KeratinoSens	sheet=Data_invitro; excel_row=4430; Record_ID=skin_sensitization_invitro_1000; Data_Type=In Vitro; Internal_Data_Source=KeratinoSens2015; Mixture=Chemical; DTXSID=DTXSID9021138; Assay=KeratinoSens; Endpoint=Imax; Reported_Response=52.887; Reported_Response_Unit=Unitless; Response=52.887; Response_Unit=Ratio; Reference=Joint Research Centre of the European Union 2014; URL_CompTox=https://comptox.epa.gov/dashboard/chemical/details/DTXSID9021138
NTP_ICE_skin_sensitization	Imax	76.003	ratio	-	Dermal	-	In Vitro; KeratinoSens2015; KeratinoSens	sheet=Data_invitro; excel_row=4431; Record_ID=skin_sensitization_invitro_995; Data_Type=In Vitro; Internal_Data_Source=KeratinoSens2015; Mixture=Chemical; DTXSID=DTXSID9021138; Assay=KeratinoSens; Endpoint=Imax; Reported_Response=76.003; Reported_Response_Unit=Unitless; Response=76.003; Response_Unit=Ratio; Reference=Joint Research Centre of the European Union 2014; URL_CompTox=https://comptox.epa.gov/dashboard/chemical/details/DTXSID9021138
NTP_ICE_skin_sensitization	Imax	11.44	ratio	-	Dermal	-	In Vitro; Urbisch_SkinSensitization2020; LuSens	sheet=Data_invitro; excel_row=7900; Record_ID=skin_sensitization_invitro_1855; Data_Type=In Vitro; Internal_Data_Source=Urbisch_SkinSensitization2020; Mixture=Chemical; DTXSID=DTXSID9021138; Assay=LuSens; Endpoint=Imax; Reported_Response=11.43842112; Reported_Response_Unit=Unitless; Response=11.44; Response_Unit=Ratio; Reference=Urbisch et al. 2015; 25541156; 10.1016/j.yrtph.2014.12.008; URL_CompTox=https://comptox.epa.gov/dashboard/chemical/details/DTXSID9021138
NTP_ICE_skin_sensitization	Incidence of positive responses	29.17	%	Human	Dermal	-	In Vivo; HPPT2020WIP; Human Maximization Test	sheet=Data_invivo; excel_row=3054; Record_ID=skin_sensitization_invivo_801; Data_Type=In Vivo; Internal_Data_Source=HPPT2020WIP; Concentration=0.2; Concentration_Units=%; Mixture=Chemical; DTXSID=DTXSID9021138; Assay=Human Maximization Test; Endpoint=Incidence of positive responses; Response=29.17; Response_Unit=%; Species=Human; Route=Dermal; Reference=Kligman 1966; 5924293; 10.1038/jid.1966.159; URL_CompTox=https://comptox.epa.gov/dashboard/chemical/details/DTXSID9021138
NTP_ICE_skin_sensitization	Incidence of positive responses	33.33	%	Human	Dermal	-	In Vivo; HPPT2020WIP; Human Maximization Test	sheet=Data_invivo; excel_row=3068; Record_ID=skin_sensitization_invivo_803; Data_Type=In Vivo; Internal_Data_Source=HPPT2020WIP; Concentration=0.2; Concentration_Units=%; Mixture=Chemical; DTXSID=DTXSID9021138; Assay=Human Maximization Test; Endpoint=Incidence of positive responses; Response=33.33; Response_Unit=%; Species=Human; Route=Dermal; Reference=Kligman 1966; 5924293; 10.1038/jid.1966.159; URL_CompTox=https://comptox.epa.gov/dashboard/chemical/details/DTXSID9021138
NTP_ICE_skin_sensitization	Incidence of positive responses	20.83	%	Human	Dermal	-	In Vivo; HPPT2020WIP; Human Maximization Test	sheet=Data_invivo; excel_row=3081; Record_ID=skin_sensitization_invivo_799; Data_Type=In Vivo; Internal_Data_Source=HPPT2020WIP; Concentration=0.1; Concentration_Units=%; Mixture=Chemical; DTXSID=DTXSID9021138; Assay=Human Maximization Test; Endpoint=Incidence of positive responses; Response=20.83; Response_Unit=%; Species=Human; Route=Dermal; Reference=Kligman 1966; 5924293; 10.1038/jid.1966.159\|Akkan et al. 2003; Not available; Not available\|Schneider and Akkan 2004; 15135206; 10.1016/j.yrtph.2004.02.002; URL_CompTox=https://comptox.epa.gov/dashboard/chemical/details/DTXSID9021138
NTP_ICE_skin_sensitization	Incidence of positive responses	43.48	%	Human	Dermal	-	In Vivo; HPPT2020WIP; Human Maximization Test	sheet=Data_invivo; excel_row=3082; Record_ID=skin_sensitization_invivo_805; Data_Type=In Vivo; Internal_Data_Source=HPPT2020WIP; Concentration=0.2; Concentration_Units=%; Mixture=Chemical; DTXSID=DTXSID9021138; Assay=Human Maximization Test; Endpoint=Incidence of positive responses; Response=43.48; Response_Unit=%; Species=Human; Route=Dermal; Reference=Kligman 1966; 5924293; 10.1038/jid.1966.159; URL_CompTox=https://comptox.epa.gov/dashboard/chemical/details/DTXSID9021138
NTP_ICE_skin_sensitization	Incidence of positive responses	68	%	Human	Dermal	-	In Vivo; HPPT2020WIP; Human Maximization Test	sheet=Data_invivo; excel_row=3094; Record_ID=skin_sensitization_invivo_806; Data_Type=In Vivo; Internal_Data_Source=HPPT2020WIP; Concentration=1.0; Concentration_Units=%; Mixture=Chemical; DTXSID=DTXSID9021138; Assay=Human Maximization Test; Endpoint=Incidence of positive responses; Response=68; Response_Unit=%; Species=Human; Route=Dermal; Reference=Kligman 1966; 5924293; 10.1038/jid.1966.159; URL_CompTox=https://comptox.epa.gov/dashboard/chemical/details/DTXSID9021138
NTP_ICE_skin_sensitization	Incidence of positive responses	91.67	%	Human	Dermal	-	In Vivo; HPPT2020WIP; Human Maximization Test	sheet=Data_invivo; excel_row=3108; Record_ID=skin_sensitization_invivo_808; Data_Type=In Vivo; Internal_Data_Source=HPPT2020WIP; Concentration=5.0; Concentration_Units=%; Mixture=Chemical; DTXSID=DTXSID9021138; Assay=Human Maximization Test; Endpoint=Incidence of positive responses; Response=91.67; Response_Unit=%; Species=Human; Route=Dermal; Reference=Kligman 1966; 5924293; 10.1038/jid.1966.159; URL_CompTox=https://comptox.epa.gov/dashboard/chemical/details/DTXSID9021138
NTP_ICE_skin_sensitization	Incidence of positive responses	100	%	Human	Dermal	-	In Vivo; HPPT2020WIP; Human Maximization Test	sheet=Data_invivo; excel_row=3110; Record_ID=skin_sensitization_invivo_809; Data_Type=In Vivo; Internal_Data_Source=HPPT2020WIP; Concentration=10.0; Concentration_Units=%; Mixture=Chemical; DTXSID=DTXSID9021138; Assay=Human Maximization Test; Endpoint=Incidence of positive responses; Response=100; Response_Unit=%; Species=Human; Route=Dermal; Reference=Kligman 1966; 5924293; 10.1038/jid.1966.159; URL_CompTox=https://comptox.epa.gov/dashboard/chemical/details/DTXSID9021138
NTP_ICE_skin_sensitization	Incidence of positive responses	96	%	Human	Dermal	-	In Vivo; HPPT2020WIP; Human Maximization Test	sheet=Data_invivo; excel_row=3122; Record_ID=skin_sensitization_invivo_807; Data_Type=In Vivo; Internal_Data_Source=HPPT2020WIP; Concentration=5.0; Concentration_Units=%; Mixture=Chemical; DTXSID=DTXSID9021138; Assay=Human Maximization Test; Endpoint=Incidence of positive responses; Response=96; Response_Unit=%; Species=Human; Route=Dermal; Reference=Kligman 1966; 5924293; 10.1038/jid.1966.159; URL_CompTox=https://comptox.epa.gov/dashboard/chemical/details/DTXSID9021138
NTP_ICE_skin_sensitization	Incidence of positive responses	11.22	%	Human	Dermal	-	In Vivo; HPPT2020WIP; Human Repeat Insult Patch Test	sheet=Data_invivo; excel_row=3137; Record_ID=skin_sensitization_invivo_812; Data_Type=In Vivo; Internal_Data_Source=HPPT2020WIP; Concentration=0.1; Concentration_Units=%; Mixture=Chemical; DTXSID=DTXSID9021138; Assay=Human Repeat Insult Patch Test; Endpoint=Incidence of positive responses; Response=11.22; Response_Unit=%; Species=Human; Route=Dermal; Reference=Marzulli and Maibach 1974; 4459237; 10.1016/0015-6264(74)90367-8\|Gerberick et al. 2001; 11526521; 10.1053/ajcd.2001.23926\|Akkan et al. 2003; Not available; Not available\|Griem et al. 2003; 14623479; 10.1016/j.yrtph.2003.07.001\|Schneider and Akkan 2004; 15135206; 10.1016/j.yrtph.2004.02.002\|Basketter et al. 2005; 16283904; 10.1111/j.0105-1873.2005.00707.x\|ICCVAM 2009; Not available; https://ntp.niehs.nih.gov/iccvam/docs/immunotox_docs/llna-ps/llnaperfstds.pdf; URL_CompTox=https://comptox.epa.gov/dashboard/chemical/details/DTXSID9021138
NTP_ICE_skin_sensitization	Incidence of positive responses	53.41	%	Human	Dermal	-	In Vivo; HPPT2020WIP; Human Repeat Insult Patch Test	sheet=Data_invivo; excel_row=3152; Record_ID=skin_sensitization_invivo_814; Data_Type=In Vivo; Internal_Data_Source=HPPT2020WIP; Concentration=1.0; Concentration_Units=%; Mixture=Chemical; DTXSID=DTXSID9021138; Assay=Human Repeat Insult Patch Test; Endpoint=Incidence of positive responses; Response=53.41; Response_Unit=%; Species=Human; Route=Dermal; Reference=Marzulli and Maibach 1974; 4459237; 10.1016/0015-6264(74)90367-8\|Gerberick et al. 2001; 11526521; 10.1053/ajcd.2001.23926\|Akkan et al. 2003; Not available; Not available\|Griem et al. 2003; 14623479; 10.1016/j.yrtph.2003.07.001\|Schneider and Akkan 2004; 15135206; 10.1016/j.yrtph.2004.02.002\|Basketter et al. 2005; 16283904; 10.1111/j.0105-1873.2005.00707.x\|ICCVAM 2009; Not available; https://ntp.niehs.nih.gov/iccvam/docs/immunotox_docs/llna-ps/llnaperfstds.pdf; URL_CompTox=https://comptox.epa.gov/dashboard/chemical/details/DTXSID9021138
NTP_ICE_skin_sensitization	Incidence of positive responses	7.216	%	Human	Dermal	-	In Vivo; HPPT2020WIP; Human Repeat Insult Patch Test	sheet=Data_invivo; excel_row=3159; Record_ID=skin_sensitization_invivo_811; Data_Type=In Vivo; Internal_Data_Source=HPPT2020WIP; Concentration=0.01; Concentration_Units=%; Mixture=Chemical; DTXSID=DTXSID9021138; Assay=Human Repeat Insult Patch Test; Endpoint=Incidence of positive responses; Response=7.216; Response_Unit=%; Species=Human; Route=Dermal; Reference=Marzulli and Maibach 1974; 4459237; 10.1016/0015-6264(74)90367-8\|Gerberick et al. 2001; 11526521; 10.1053/ajcd.2001.23926\|Akkan et al. 2003; Not available; Not available\|Griem et al. 2003; 14623479; 10.1016/j.yrtph.2003.07.001\|Schneider and Akkan 2004; 15135206; 10.1016/j.yrtph.2004.02.002\|Basketter et al. 2005; 16283904; 10.1111/j.0105-1873.2005.00707.x\|ICCVAM 2009; Not available; https://ntp.niehs.nih.gov/iccvam/docs/immunotox_docs/llna-ps/llnaperfstds.pdf; URL_CompTox=https://comptox.epa.gov/dashboard/chemical/details/DTXSID9021138
NTP_ICE_skin_sensitization	Induction dose per skin area	124.1	ug/cm2	Human	Dermal	-	In Vivo; HPPT2020WIP; Human Maximization Test	sheet=Data_invivo; excel_row=3052; Record_ID=skin_sensitization_invivo_801; Data_Type=In Vivo; Internal_Data_Source=HPPT2020WIP; Concentration=0.2; Concentration_Units=%; Mixture=Chemical; DTXSID=DTXSID9021138; Assay=Human Maximization Test; Endpoint=Induction dose per skin area; Response=124.1; Response_Unit=ug/cm2; Species=Human; Route=Dermal; Reference=Kligman 1966; 5924293; 10.1038/jid.1966.159; URL_CompTox=https://comptox.epa.gov/dashboard/chemical/details/DTXSID9021138
NTP_ICE_skin_sensitization	Induction dose per skin area	62.07	ug/cm2	Human	Dermal	-	In Vivo; HPPT2020WIP; Human Maximization Test	sheet=Data_invivo; excel_row=3079; Record_ID=skin_sensitization_invivo_799; Data_Type=In Vivo; Internal_Data_Source=HPPT2020WIP; Concentration=0.1; Concentration_Units=%; Mixture=Chemical; DTXSID=DTXSID9021138; Assay=Human Maximization Test; Endpoint=Induction dose per skin area; Response=62.07; Response_Unit=ug/cm2; Species=Human; Route=Dermal; Reference=Kligman 1966; 5924293; 10.1038/jid.1966.159\|Akkan et al. 2003; Not available; Not available\|Schneider and Akkan 2004; 15135206; 10.1016/j.yrtph.2004.02.002; URL_CompTox=https://comptox.epa.gov/dashboard/chemical/details/DTXSID9021138
NTP_ICE_skin_sensitization	Induction dose per skin area	620.7	ug/cm2	Human	Dermal	-	In Vivo; HPPT2020WIP; Human Maximization Test	sheet=Data_invivo; excel_row=3093; Record_ID=skin_sensitization_invivo_806; Data_Type=In Vivo; Internal_Data_Source=HPPT2020WIP; Concentration=1.0; Concentration_Units=%; Mixture=Chemical; DTXSID=DTXSID9021138; Assay=Human Maximization Test; Endpoint=Induction dose per skin area; Response=620.7; Response_Unit=ug/cm2; Species=Human; Route=Dermal; Reference=Kligman 1966; 5924293; 10.1038/jid.1966.159; URL_CompTox=https://comptox.epa.gov/dashboard/chemical/details/DTXSID9021138
NTP_ICE_skin_sensitization	Induction dose per skin area	3103	ug/cm2	Human	Dermal	-	In Vivo; HPPT2020WIP; Human Maximization Test	sheet=Data_invivo; excel_row=3105; Record_ID=skin_sensitization_invivo_808; Data_Type=In Vivo; Internal_Data_Source=HPPT2020WIP; Concentration=5.0; Concentration_Units=%; Mixture=Chemical; DTXSID=DTXSID9021138; Assay=Human Maximization Test; Endpoint=Induction dose per skin area; Response=3103; Response_Unit=ug/cm2; Species=Human; Route=Dermal; Reference=Kligman 1966; 5924293; 10.1038/jid.1966.159; URL_CompTox=https://comptox.epa.gov/dashboard/chemical/details/DTXSID9021138
NTP_ICE_skin_sensitization	Induction dose per skin area	6207	ug/cm2	Human	Dermal	-	In Vivo; HPPT2020WIP; Human Maximization Test	sheet=Data_invivo; excel_row=3107; Record_ID=skin_sensitization_invivo_809; Data_Type=In Vivo; Internal_Data_Source=HPPT2020WIP; Concentration=10.0; Concentration_Units=%; Mixture=Chemical; DTXSID=DTXSID9021138; Assay=Human Maximization Test; Endpoint=Induction dose per skin area; Response=6207; Response_Unit=ug/cm2; Species=Human; Route=Dermal; Reference=Kligman 1966; 5924293; 10.1038/jid.1966.159; URL_CompTox=https://comptox.epa.gov/dashboard/chemical/details/DTXSID9021138
NTP_ICE_skin_sensitization	Induction dose per skin area	69.75	ug/cm2	Human	Dermal	-	In Vivo; HPPT2020WIP; Human Repeat Insult Patch Test	sheet=Data_invivo; excel_row=3135; Record_ID=skin_sensitization_invivo_812; Data_Type=In Vivo; Internal_Data_Source=HPPT2020WIP; Concentration=0.1; Concentration_Units=%; Mixture=Chemical; DTXSID=DTXSID9021138; Assay=Human Repeat Insult Patch Test; Endpoint=Induction dose per skin area; Response=69.75; Response_Unit=ug/cm2; Species=Human; Route=Dermal; Reference=Marzulli and Maibach 1974; 4459237; 10.1016/0015-6264(74)90367-8\|Gerberick et al. 2001; 11526521; 10.1053/ajcd.2001.23926\|Akkan et al. 2003; Not available; Not available\|Griem et al. 2003; 14623479; 10.1016/j.yrtph.2003.07.001\|Schneider and Akkan 2004; 15135206; 10.1016/j.yrtph.2004.02.002\|Basketter et al. 2005; 16283904; 10.1111/j.0105-1873.2005.00707.x\|ICCVAM 2009; Not available; https://ntp.niehs.nih.gov/iccvam/docs/immunotox_docs/llna-ps/llnaperfstds.pdf; URL_CompTox=https://comptox.epa.gov/dashboard/chemical/details/DTXSID9021138
NTP_ICE_skin_sensitization	Induction dose per skin area	15520	ug/cm2	Human	Dermal	-	In Vivo; HPPT2020WIP; Human Maximization Test	sheet=Data_invivo; excel_row=3140; Record_ID=skin_sensitization_invivo_813; Data_Type=In Vivo; Internal_Data_Source=HPPT2020WIP; Concentration=25.0; Concentration_Units=%; Mixture=Chemical; DTXSID=DTXSID9021138; Assay=Human Maximization Test; Endpoint=Induction dose per skin area; Response=15520; Response_Unit=ug/cm2; Species=Human; Route=Dermal; Reference=Kligman 1966; 5924293; 10.1038/jid.1966.159; URL_CompTox=https://comptox.epa.gov/dashboard/chemical/details/DTXSID9021138
NTP_ICE_skin_sensitization	Induction dose per skin area	697.5	ug/cm2	Human	Dermal	-	In Vivo; HPPT2020WIP; Human Repeat Insult Patch Test	sheet=Data_invivo; excel_row=3150; Record_ID=skin_sensitization_invivo_814; Data_Type=In Vivo; Internal_Data_Source=HPPT2020WIP; Concentration=1.0; Concentration_Units=%; Mixture=Chemical; DTXSID=DTXSID9021138; Assay=Human Repeat Insult Patch Test; Endpoint=Induction dose per skin area; Response=697.5; Response_Unit=ug/cm2; Species=Human; Route=Dermal; Reference=Marzulli and Maibach 1974; 4459237; 10.1016/0015-6264(74)90367-8\|Gerberick et al. 2001; 11526521; 10.1053/ajcd.2001.23926\|Akkan et al. 2003; Not available; Not available\|Griem et al. 2003; 14623479; 10.1016/j.yrtph.2003.07.001\|Schneider and Akkan 2004; 15135206; 10.1016/j.yrtph.2004.02.002\|Basketter et al. 2005; 16283904; 10.1111/j.0105-1873.2005.00707.x\|ICCVAM 2009; Not available; https://ntp.niehs.nih.gov/iccvam/docs/immunotox_docs/llna-ps/llnaperfstds.pdf; URL_CompTox=https://comptox.epa.gov/dashboard/chemical/details/DTXSID9021138
NTP_ICE_skin_sensitization	Induction dose per skin area	6.975	ug/cm2	Human	Dermal	-	In Vivo; HPPT2020WIP; Human Repeat Insult Patch Test	sheet=Data_invivo; excel_row=3157; Record_ID=skin_sensitization_invivo_811; Data_Type=In Vivo; Internal_Data_Source=HPPT2020WIP; Concentration=0.01; Concentration_Units=%; Mixture=Chemical; DTXSID=DTXSID9021138; Assay=Human Repeat Insult Patch Test; Endpoint=Induction dose per skin area; Response=6.975; Response_Unit=ug/cm2; Species=Human; Route=Dermal; Reference=Marzulli and Maibach 1974; 4459237; 10.1016/0015-6264(74)90367-8\|Gerberick et al. 2001; 11526521; 10.1053/ajcd.2001.23926\|Akkan et al. 2003; Not available; Not available\|Griem et al. 2003; 14623479; 10.1016/j.yrtph.2003.07.001\|Schneider and Akkan 2004; 15135206; 10.1016/j.yrtph.2004.02.002\|Basketter et al. 2005; 16283904; 10.1111/j.0105-1873.2005.00707.x\|ICCVAM 2009; Not available; https://ntp.niehs.nih.gov/iccvam/docs/immunotox_docs/llna-ps/llnaperfstds.pdf; URL_CompTox=https://comptox.epa.gov/dashboard/chemical/details/DTXSID9021138
NTP_ICE_skin_sensitization	Induction dose per skin area, 5% incidence of positive responses	14.9	ug/cm2	Human	Dermal	-	In Vivo; HPPT2020WIP; Human Maximization Test	sheet=Data_invivo; excel_row=3048; Record_ID=skin_sensitization_invivo_799; Data_Type=In Vivo; Internal_Data_Source=HPPT2020WIP; Concentration=0.1; Concentration_Units=%; Mixture=Chemical; DTXSID=DTXSID9021138; Assay=Human Maximization Test; Endpoint=Induction dose per skin area, 5% incidence of positive responses; Response=14.9; Response_Unit=ug/cm2; Species=Human; Route=Dermal; Reference=Kligman 1966; 5924293; 10.1038/jid.1966.159\|Akkan et al. 2003; Not available; Not available\|Schneider and Akkan 2004; 15135206; 10.1016/j.yrtph.2004.02.002; URL_CompTox=https://comptox.epa.gov/dashboard/chemical/details/DTXSID9021138
NTP_ICE_skin_sensitization	Induction dose per skin area, 5% incidence of positive responses	21.28	ug/cm2	Human	Dermal	-	In Vivo; HPPT2020WIP; Human Maximization Test	sheet=Data_invivo; excel_row=3063; Record_ID=skin_sensitization_invivo_801; Data_Type=In Vivo; Internal_Data_Source=HPPT2020WIP; Concentration=0.2; Concentration_Units=%; Mixture=Chemical; DTXSID=DTXSID9021138; Assay=Human Maximization Test; Endpoint=Induction dose per skin area, 5% incidence of positive responses; Response=21.28; Response_Unit=ug/cm2; Species=Human; Route=Dermal; Reference=Kligman 1966; 5924293; 10.1038/jid.1966.159; URL_CompTox=https://comptox.epa.gov/dashboard/chemical/details/DTXSID9021138
NTP_ICE_skin_sensitization	Induction dose per skin area, 5% incidence of positive responses	18.62	ug/cm2	Human	Dermal	-	In Vivo; HPPT2020WIP; Human Maximization Test	sheet=Data_invivo; excel_row=3077; Record_ID=skin_sensitization_invivo_803; Data_Type=In Vivo; Internal_Data_Source=HPPT2020WIP; Concentration=0.2; Concentration_Units=%; Mixture=Chemical; DTXSID=DTXSID9021138; Assay=Human Maximization Test; Endpoint=Induction dose per skin area, 5% incidence of positive responses; Response=18.62; Response_Unit=ug/cm2; Species=Human; Route=Dermal; Reference=Kligman 1966; 5924293; 10.1038/jid.1966.159; URL_CompTox=https://comptox.epa.gov/dashboard/chemical/details/DTXSID9021138
NTP_ICE_skin_sensitization	Induction dose per skin area, 5% incidence of positive responses	14.28	ug/cm2	Human	Dermal	-	In Vivo; HPPT2020WIP; Human Maximization Test	sheet=Data_invivo; excel_row=3091; Record_ID=skin_sensitization_invivo_805; Data_Type=In Vivo; Internal_Data_Source=HPPT2020WIP; Concentration=0.2; Concentration_Units=%; Mixture=Chemical; DTXSID=DTXSID9021138; Assay=Human Maximization Test; Endpoint=Induction dose per skin area, 5% incidence of positive responses; Response=14.28; Response_Unit=ug/cm2; Species=Human; Route=Dermal; Reference=Kligman 1966; 5924293; 10.1038/jid.1966.159; URL_CompTox=https://comptox.epa.gov/dashboard/chemical/details/DTXSID9021138
NTP_ICE_skin_sensitization	Induction dose per skin area, 5% incidence of positive responses	45.64	ug/cm2	Human	Dermal	-	In Vivo; HPPT2020WIP; Human Maximization Test	sheet=Data_invivo; excel_row=3101; Record_ID=skin_sensitization_invivo_806; Data_Type=In Vivo; Internal_Data_Source=HPPT2020WIP; Concentration=1.0; Concentration_Units=%; Mixture=Chemical; DTXSID=DTXSID9021138; Assay=Human Maximization Test; Endpoint=Induction dose per skin area, 5% incidence of positive responses; Response=45.64; Response_Unit=ug/cm2; Species=Human; Route=Dermal; Reference=Kligman 1966; 5924293; 10.1038/jid.1966.159; URL_CompTox=https://comptox.epa.gov/dashboard/chemical/details/DTXSID9021138
NTP_ICE_skin_sensitization	Induction dose per skin area, 5% incidence of positive responses	161.6	ug/cm2	Human	Dermal	-	In Vivo; HPPT2020WIP; Human Maximization Test	sheet=Data_invivo; excel_row=3104; Record_ID=skin_sensitization_invivo_807; Data_Type=In Vivo; Internal_Data_Source=HPPT2020WIP; Concentration=5.0; Concentration_Units=%; Mixture=Chemical; DTXSID=DTXSID9021138; Assay=Human Maximization Test; Endpoint=Induction dose per skin area, 5% incidence of positive responses; Response=161.6; Response_Unit=ug/cm2; Species=Human; Route=Dermal; Reference=Kligman 1966; 5924293; 10.1038/jid.1966.159; URL_CompTox=https://comptox.epa.gov/dashboard/chemical/details/DTXSID9021138
NTP_ICE_skin_sensitization	Induction dose per skin area, 5% incidence of positive responses	169.3	ug/cm2	Human	Dermal	-	In Vivo; HPPT2020WIP; Human Maximization Test	sheet=Data_invivo; excel_row=3117; Record_ID=skin_sensitization_invivo_808; Data_Type=In Vivo; Internal_Data_Source=HPPT2020WIP; Concentration=5.0; Concentration_Units=%; Mixture=Chemical; DTXSID=DTXSID9021138; Assay=Human Maximization Test; Endpoint=Induction dose per skin area, 5% incidence of positive responses; Response=169.3; Response_Unit=ug/cm2; Species=Human; Route=Dermal; Reference=Kligman 1966; 5924293; 10.1038/jid.1966.159; URL_CompTox=https://comptox.epa.gov/dashboard/chemical/details/DTXSID9021138
NTP_ICE_skin_sensitization	Induction dose per skin area, 5% incidence of positive responses	310.3	ug/cm2	Human	Dermal	-	In Vivo; HPPT2020WIP; Human Maximization Test	sheet=Data_invivo; excel_row=3121; Record_ID=skin_sensitization_invivo_809; Data_Type=In Vivo; Internal_Data_Source=HPPT2020WIP; Concentration=10.0; Concentration_Units=%; Mixture=Chemical; DTXSID=DTXSID9021138; Assay=Human Maximization Test; Endpoint=Induction dose per skin area, 5% incidence of positive responses; Response=310.3; Response_Unit=ug/cm2; Species=Human; Route=Dermal; Reference=Kligman 1966; 5924293; 10.1038/jid.1966.159; URL_CompTox=https://comptox.epa.gov/dashboard/chemical/details/DTXSID9021138
NTP_ICE_skin_sensitization	Induction dose per skin area, 5% incidence of positive responses	4.833	ug/cm2	Human	Dermal	-	In Vivo; HPPT2020WIP; Human Repeat Insult Patch Test	sheet=Data_invivo; excel_row=3131; Record_ID=skin_sensitization_invivo_811; Data_Type=In Vivo; Internal_Data_Source=HPPT2020WIP; Concentration=0.01; Concentration_Units=%; Mixture=Chemical; DTXSID=DTXSID9021138; Assay=Human Repeat Insult Patch Test; Endpoint=Induction dose per skin area, 5% incidence of positive responses; Response=4.833; Response_Unit=ug/cm2; Species=Human; Route=Dermal; Reference=Marzulli and Maibach 1974; 4459237; 10.1016/0015-6264(74)90367-8\|Gerberick et al. 2001; 11526521; 10.1053/ajcd.2001.23926\|Akkan et al. 2003; Not available; Not available\|Griem et al. 2003; 14623479; 10.1016/j.yrtph.2003.07.001\|Schneider and Akkan 2004; 15135206; 10.1016/j.yrtph.2004.02.002\|Basketter et al. 2005; 16283904; 10.1111/j.0105-1873.2005.00707.x\|ICCVAM 2009; Not available; https://ntp.niehs.nih.gov/iccvam/docs/immunotox_docs/llna-ps/llnaperfstds.pdf; URL_CompTox=https://comptox.epa.gov/dashboard/chemical/details/DTXSID9021138
NTP_ICE_skin_sensitization	Induction dose per skin area, 5% incidence of positive responses	31.07	ug/cm2	Human	Dermal	-	In Vivo; HPPT2020WIP; Human Repeat Insult Patch Test	sheet=Data_invivo; excel_row=3146; Record_ID=skin_sensitization_invivo_812; Data_Type=In Vivo; Internal_Data_Source=HPPT2020WIP; Concentration=0.1; Concentration_Units=%; Mixture=Chemical; DTXSID=DTXSID9021138; Assay=Human Repeat Insult Patch Test; Endpoint=Induction dose per skin area, 5% incidence of positive responses; Response=31.07; Response_Unit=ug/cm2; Species=Human; Route=Dermal; Reference=Marzulli and Maibach 1974; 4459237; 10.1016/0015-6264(74)90367-8\|Gerberick et al. 2001; 11526521; 10.1053/ajcd.2001.23926\|Akkan et al. 2003; Not available; Not available\|Griem et al. 2003; 14623479; 10.1016/j.yrtph.2003.07.001\|Schneider and Akkan 2004; 15135206; 10.1016/j.yrtph.2004.02.002\|Basketter et al. 2005; 16283904; 10.1111/j.0105-1873.2005.00707.x\|ICCVAM 2009; Not available; https://ntp.niehs.nih.gov/iccvam/docs/immunotox_docs/llna-ps/llnaperfstds.pdf; URL_CompTox=https://comptox.epa.gov/dashboard/chemical/details/DTXSID9021138
NTP_ICE_skin_sensitization	Induction dose per skin area, 5% incidence of positive responses	65.3	ug/cm2	Human	Dermal	-	In Vivo; HPPT2020WIP; Human Repeat Insult Patch Test	sheet=Data_invivo; excel_row=3161; Record_ID=skin_sensitization_invivo_814; Data_Type=In Vivo; Internal_Data_Source=HPPT2020WIP; Concentration=1.0; Concentration_Units=%; Mixture=Chemical; DTXSID=DTXSID9021138; Assay=Human Repeat Insult Patch Test; Endpoint=Induction dose per skin area, 5% incidence of positive responses; Response=65.3; Response_Unit=ug/cm2; Species=Human; Route=Dermal; Reference=Marzulli and Maibach 1974; 4459237; 10.1016/0015-6264(74)90367-8\|Gerberick et al. 2001; 11526521; 10.1053/ajcd.2001.23926\|Akkan et al. 2003; Not available; Not available\|Griem et al. 2003; 14623479; 10.1016/j.yrtph.2003.07.001\|Schneider and Akkan 2004; 15135206; 10.1016/j.yrtph.2004.02.002\|Basketter et al. 2005; 16283904; 10.1111/j.0105-1873.2005.00707.x\|ICCVAM 2009; Not available; https://ntp.niehs.nih.gov/iccvam/docs/immunotox_docs/llna-ps/llnaperfstds.pdf; URL_CompTox=https://comptox.epa.gov/dashboard/chemical/details/DTXSID9021138
NTP_ICE_skin_sensitization	Induction dose per skin area, one positive response	17.73	ug/cm2	Human	Dermal	-	In Vivo; HPPT2020WIP; Human Maximization Test	sheet=Data_invivo; excel_row=3060; Record_ID=skin_sensitization_invivo_801; Data_Type=In Vivo; Internal_Data_Source=HPPT2020WIP; Concentration=0.2; Concentration_Units=%; Mixture=Chemical; DTXSID=DTXSID9021138; Assay=Human Maximization Test; Endpoint=Induction dose per skin area, one positive response; Response=17.73; Response_Unit=ug/cm2; Species=Human; Route=Dermal; Reference=Kligman 1966; 5924293; 10.1038/jid.1966.159; URL_CompTox=https://comptox.epa.gov/dashboard/chemical/details/DTXSID9021138
NTP_ICE_skin_sensitization	Induction dose per skin area, one positive response	15.52	ug/cm2	Human	Dermal	-	In Vivo; HPPT2020WIP; Human Maximization Test	sheet=Data_invivo; excel_row=3073; Record_ID=skin_sensitization_invivo_803; Data_Type=In Vivo; Internal_Data_Source=HPPT2020WIP; Concentration=0.2; Concentration_Units=%; Mixture=Chemical; DTXSID=DTXSID9021138; Assay=Human Maximization Test; Endpoint=Induction dose per skin area, one positive response; Response=15.52; Response_Unit=ug/cm2; Species=Human; Route=Dermal; Reference=Kligman 1966; 5924293; 10.1038/jid.1966.159; URL_CompTox=https://comptox.epa.gov/dashboard/chemical/details/DTXSID9021138
NTP_ICE_skin_sensitization	Induction dose per skin area, one positive response	12.41	ug/cm2	Human	Dermal	-	In Vivo; HPPT2020WIP; Human Maximization Test	sheet=Data_invivo; excel_row=3087; Record_ID=skin_sensitization_invivo_805; Data_Type=In Vivo; Internal_Data_Source=HPPT2020WIP; Concentration=0.2; Concentration_Units=%; Mixture=Chemical; DTXSID=DTXSID9021138; Assay=Human Maximization Test; Endpoint=Induction dose per skin area, one positive response; Response=12.41; Response_Unit=ug/cm2; Species=Human; Route=Dermal; Reference=Kligman 1966; 5924293; 10.1038/jid.1966.159; URL_CompTox=https://comptox.epa.gov/dashboard/chemical/details/DTXSID9021138
NTP_ICE_skin_sensitization	Induction dose per skin area, one positive response	36.51	ug/cm2	Human	Dermal	-	In Vivo; HPPT2020WIP; Human Maximization Test	sheet=Data_invivo; excel_row=3098; Record_ID=skin_sensitization_invivo_806; Data_Type=In Vivo; Internal_Data_Source=HPPT2020WIP; Concentration=1.0; Concentration_Units=%; Mixture=Chemical; DTXSID=DTXSID9021138; Assay=Human Maximization Test; Endpoint=Induction dose per skin area, one positive response; Response=36.51; Response_Unit=ug/cm2; Species=Human; Route=Dermal; Reference=Kligman 1966; 5924293; 10.1038/jid.1966.159; URL_CompTox=https://comptox.epa.gov/dashboard/chemical/details/DTXSID9021138
NTP_ICE_skin_sensitization	Induction dose per skin area, one positive response	129.3	ug/cm2	Human	Dermal	-	In Vivo; HPPT2020WIP; Human Maximization Test	sheet=Data_invivo; excel_row=3099; Record_ID=skin_sensitization_invivo_807; Data_Type=In Vivo; Internal_Data_Source=HPPT2020WIP; Concentration=5.0; Concentration_Units=%; Mixture=Chemical; DTXSID=DTXSID9021138; Assay=Human Maximization Test; Endpoint=Induction dose per skin area, one positive response; Response=129.3; Response_Unit=ug/cm2; Species=Human; Route=Dermal; Reference=Kligman 1966; 5924293; 10.1038/jid.1966.159; URL_CompTox=https://comptox.epa.gov/dashboard/chemical/details/DTXSID9021138
NTP_ICE_skin_sensitization	Induction dose per skin area, one positive response	141.1	ug/cm2	Human	Dermal	-	In Vivo; HPPT2020WIP; Human Maximization Test	sheet=Data_invivo; excel_row=3113; Record_ID=skin_sensitization_invivo_808; Data_Type=In Vivo; Internal_Data_Source=HPPT2020WIP; Concentration=5.0; Concentration_Units=%; Mixture=Chemical; DTXSID=DTXSID9021138; Assay=Human Maximization Test; Endpoint=Induction dose per skin area, one positive response; Response=141.1; Response_Unit=ug/cm2; Species=Human; Route=Dermal; Reference=Kligman 1966; 5924293; 10.1038/jid.1966.159; URL_CompTox=https://comptox.epa.gov/dashboard/chemical/details/DTXSID9021138
NTP_ICE_skin_sensitization	Induction dose per skin area, one positive response	258.6	ug/cm2	Human	Dermal	-	In Vivo; HPPT2020WIP; Human Maximization Test	sheet=Data_invivo; excel_row=3116; Record_ID=skin_sensitization_invivo_809; Data_Type=In Vivo; Internal_Data_Source=HPPT2020WIP; Concentration=10.0; Concentration_Units=%; Mixture=Chemical; DTXSID=DTXSID9021138; Assay=Human Maximization Test; Endpoint=Induction dose per skin area, one positive response; Response=258.6; Response_Unit=ug/cm2; Species=Human; Route=Dermal; Reference=Kligman 1966; 5924293; 10.1038/jid.1966.159; URL_CompTox=https://comptox.epa.gov/dashboard/chemical/details/DTXSID9021138
NTP_ICE_skin_sensitization	Induction dose per skin area, one positive response	0.9964	ug/cm2	Human	Dermal	-	In Vivo; HPPT2020WIP; Human Repeat Insult Patch Test	sheet=Data_invivo; excel_row=3127; Record_ID=skin_sensitization_invivo_811; Data_Type=In Vivo; Internal_Data_Source=HPPT2020WIP; Concentration=0.01; Concentration_Units=%; Mixture=Chemical; DTXSID=DTXSID9021138; Assay=Human Repeat Insult Patch Test; Endpoint=Induction dose per skin area, one positive response; Response=0.9964; Response_Unit=ug/cm2; Species=Human; Route=Dermal; Reference=Marzulli and Maibach 1974; 4459237; 10.1016/0015-6264(74)90367-8\|Gerberick et al. 2001; 11526521; 10.1053/ajcd.2001.23926\|Akkan et al. 2003; Not available; Not available\|Griem et al. 2003; 14623479; 10.1016/j.yrtph.2003.07.001\|Schneider and Akkan 2004; 15135206; 10.1016/j.yrtph.2004.02.002\|Basketter et al. 2005; 16283904; 10.1111/j.0105-1873.2005.00707.x\|ICCVAM 2009; Not available; https://ntp.niehs.nih.gov/iccvam/docs/immunotox_docs/llna-ps/llnaperfstds.pdf; URL_CompTox=https://comptox.epa.gov/dashboard/chemical/details/DTXSID9021138
NTP_ICE_skin_sensitization	Induction dose per skin area, one positive response	6.341	ug/cm2	Human	Dermal	-	In Vivo; HPPT2020WIP; Human Repeat Insult Patch Test	sheet=Data_invivo; excel_row=3142; Record_ID=skin_sensitization_invivo_812; Data_Type=In Vivo; Internal_Data_Source=HPPT2020WIP; Concentration=0.1; Concentration_Units=%; Mixture=Chemical; DTXSID=DTXSID9021138; Assay=Human Repeat Insult Patch Test; Endpoint=Induction dose per skin area, one positive response; Response=6.341; Response_Unit=ug/cm2; Species=Human; Route=Dermal; Reference=Marzulli and Maibach 1974; 4459237; 10.1016/0015-6264(74)90367-8\|Gerberick et al. 2001; 11526521; 10.1053/ajcd.2001.23926\|Akkan et al. 2003; Not available; Not available\|Griem et al. 2003; 14623479; 10.1016/j.yrtph.2003.07.001\|Schneider and Akkan 2004; 15135206; 10.1016/j.yrtph.2004.02.002\|Basketter et al. 2005; 16283904; 10.1111/j.0105-1873.2005.00707.x\|ICCVAM 2009; Not available; https://ntp.niehs.nih.gov/iccvam/docs/immunotox_docs/llna-ps/llnaperfstds.pdf; URL_CompTox=https://comptox.epa.gov/dashboard/chemical/details/DTXSID9021138
NTP_ICE_skin_sensitization	Induction dose per skin area, one positive response	775.9	ug/cm2	Human	Dermal	-	In Vivo; HPPT2020WIP; Human Maximization Test	sheet=Data_invivo; excel_row=3149; Record_ID=skin_sensitization_invivo_813; Data_Type=In Vivo; Internal_Data_Source=HPPT2020WIP; Concentration=25.0; Concentration_Units=%; Mixture=Chemical; DTXSID=DTXSID9021138; Assay=Human Maximization Test; Endpoint=Induction dose per skin area, one positive response; Response=775.9; Response_Unit=ug/cm2; Species=Human; Route=Dermal; Reference=Kligman 1966; 5924293; 10.1038/jid.1966.159; URL_CompTox=https://comptox.epa.gov/dashboard/chemical/details/DTXSID9021138
NTP_ICE_skin_sensitization	Induction dose per skin area, one positive response	14.84	ug/cm2	Human	Dermal	-	In Vivo; HPPT2020WIP; Human Repeat Insult Patch Test	sheet=Data_invivo; excel_row=3158; Record_ID=skin_sensitization_invivo_814; Data_Type=In Vivo; Internal_Data_Source=HPPT2020WIP; Concentration=1.0; Concentration_Units=%; Mixture=Chemical; DTXSID=DTXSID9021138; Assay=Human Repeat Insult Patch Test; Endpoint=Induction dose per skin area, one positive response; Response=14.84; Response_Unit=ug/cm2; Species=Human; Route=Dermal; Reference=Marzulli and Maibach 1974; 4459237; 10.1016/0015-6264(74)90367-8\|Gerberick et al. 2001; 11526521; 10.1053/ajcd.2001.23926\|Akkan et al. 2003; Not available; Not available\|Griem et al. 2003; 14623479; 10.1016/j.yrtph.2003.07.001\|Schneider and Akkan 2004; 15135206; 10.1016/j.yrtph.2004.02.002\|Basketter et al. 2005; 16283904; 10.1111/j.0105-1873.2005.00707.x\|ICCVAM 2009; Not available; https://ntp.niehs.nih.gov/iccvam/docs/immunotox_docs/llna-ps/llnaperfstds.pdf; URL_CompTox=https://comptox.epa.gov/dashboard/chemical/details/DTXSID9021138
NTP_ICE_skin_sensitization	Max stimulation index	26.4	ratio	Mouse	Dermal	-	In Vivo; LLNA2013; LLNA	sheet=Data_invivo; excel_row=12860; Record_ID=skin_sensitization_invivo_488; Data_Type=In Vivo; Internal_Data_Source=LLNA2013; Mixture=Chemical; DTXSID=DTXSID9021138; Assay=LLNA; Endpoint=Max stimulation index; Response=26.4; Response_Unit=Ratio; Species=Mouse; Route=Dermal; Reference=ICCVAM 2009; Not available; https://ntp.niehs.nih.gov/iccvam/docs/immunotox_docs/llna-ps/llnaperfstds.pdf; URL_CompTox=https://comptox.epa.gov/dashboard/chemical/details/DTXSID9021138
NTP_ICE_skin_sensitization	Relative reliability score	1	unitless	Human	Dermal	-	In Vivo; HPPT2020WIP; Human Maximization Test	sheet=Data_invivo; excel_row=3050; Record_ID=skin_sensitization_invivo_799; Data_Type=In Vivo; Internal_Data_Source=HPPT2020WIP; Concentration=0.1; Concentration_Units=%; Mixture=Chemical; DTXSID=DTXSID9021138; Assay=Human Maximization Test; Endpoint=Relative reliability score; Response=1; Response_Unit=Unitless; Species=Human; Route=Dermal; Reference=Kligman 1966; 5924293; 10.1038/jid.1966.159\|Akkan et al. 2003; Not available; Not available\|Schneider and Akkan 2004; 15135206; 10.1016/j.yrtph.2004.02.002; URL_CompTox=https://comptox.epa.gov/dashboard/chemical/details/DTXSID9021138
NTP_ICE_skin_sensitization	Relative reliability score	2	unitless	Human	Dermal	-	In Vivo; HPPT2020WIP; Human Repeat Insult Patch Test	sheet=Data_invivo; excel_row=3133; Record_ID=skin_sensitization_invivo_811; Data_Type=In Vivo; Internal_Data_Source=HPPT2020WIP; Concentration=0.01; Concentration_Units=%; Mixture=Chemical; DTXSID=DTXSID9021138; Assay=Human Repeat Insult Patch Test; Endpoint=Relative reliability score; Response=2; Response_Unit=Unitless; Species=Human; Route=Dermal; Reference=Marzulli and Maibach 1974; 4459237; 10.1016/0015-6264(74)90367-8\|Gerberick et al. 2001; 11526521; 10.1053/ajcd.2001.23926\|Akkan et al. 2003; Not available; Not available\|Griem et al. 2003; 14623479; 10.1016/j.yrtph.2003.07.001\|Schneider and Akkan 2004; 15135206; 10.1016/j.yrtph.2004.02.002\|Basketter et al. 2005; 16283904; 10.1111/j.0105-1873.2005.00707.x\|ICCVAM 2009; Not available; https://ntp.niehs.nih.gov/iccvam/docs/immunotox_docs/llna-ps/llnaperfstds.pdf; URL_CompTox=https://comptox.epa.gov/dashboard/chemical/details/DTXSID9021138

SCCNFP_vision_codex 24 endpoints

Source	Endpoint Type	Value	Unit	Species	Route	Duration	Study Type	Reference
SCCNFP_vision_codex	NOAEL	=5	mg/kg bw/day	rat	oral	Sub-chronic	repeated dose toxicity	{"citation":"Ref. : 120 2","dose":"blood chemistry changes resulted in both sexes at dose level of 5 mg/kg/day or greater (increased lactate dehydrogenase and creatine phosphokinase levels). - 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 t...","effect":"blood chemistry changes resulted in both sexes at dose level of 5 mg/kg/day or greater (increased lactate dehydrogenase and creatine phosphokinase levels). - 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 NOAEL was \u0001 5 mg/kg bw/day. Ref. : 120 2.3.3. Sub-chronic 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 guideline N° 408 (1981). PPD was administered by gavage at corresponding dose levels of 2, 4, 8 and 16 mg/kg/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 twice daily for mortality/viability and once daily for clinical signs","page":5,"pdf":"out156_en.pdf","row_type":"noael_study","study_id":"out156_en_noael_001"}
SCCNFP_vision_codex	NOAEL	=4	mg/kg/day	rat	oral	12-week	NOAEL study	{"citation":"Ref. : 121 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","dose":"-related liver weights were significantly increased for males given 8 mg/kg/day and 16 mg/kg/day.","effect":"-related liver weights were significantly increased for males given 8 mg/kg/day and 16 mg/kg/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 NOAEL of PPD was established at 4 mg/kg/day. Ref. : 121 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/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 k","page":6,"pdf":"out156_en.pdf","row_type":"noael_study","study_id":"out156_en_noael_002"}
SCCNFP_vision_codex	NOAEL	=50	mg/kg bw	rat	oral	13-week	NOAEL study	{"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":"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/day respectively).","effect":"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/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. Fo","page":6,"pdf":"out156_en.pdf","row_type":"noael_study","study_id":"out156_en_noael_003"}
SCCNFP_vision_codex	NOAEL	=8	mg/kg	rabbit	dermal	13weeks	repeated dose toxicity	{"citation":"Ref. : 47 2","dose":"Food intake and body weight gain of treated group were similar to the controls.","effect":"y evaluations were conducted before and after 4, 8 and 13weeks of dosing according to a test battery consisting in motor activity and functional battery assessments. There were no mortalities or clinical signs considered related to the test article. Food intake and body weight gain of treated group were similar to the controls. Neuropathology evaluations did not reveal abnormalities within the nervous system or skeletal muscle. There was no effect of the test substance on ocular tissue. Based on these results, the NOEL was 8 mg/kg for both sexes and since the modifications observed can be assumed referring to pharmacological responses and not to neurotoxicity, the NOAEL was 16 mg/kg bw. Ref. : 47 2.3.4. Sub-chronic 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 and other hair-dye constituents were mixed with an equal volume of 6 % hydrogen peroxide. A dose of 1","page":6,"pdf":"out156_en.pdf","row_type":"noael_study","study_id":"out156_en_noael_004"}
SCCNFP_vision_codex	NOAEL	=16	mg/kg bw	rabbit	dermal	Sub-chronic	repeated dose toxicity	{"citation":"Ref. : 47 2","dose":"Food intake and body weight gain of treated group were similar to the controls.","effect":"assessments. There were no mortalities or clinical signs considered related to the test article. Food intake and body weight gain of treated group were similar to the controls. Neuropathology evaluations did not reveal abnormalities within the nervous system or skeletal muscle. There was no effect of the test substance on ocular tissue. Based on these results, the NOEL was 8 mg/kg for both sexes and since the modifications observed can be assumed referring to pharmacological responses and not to neurotoxicity, the NOAEL was 16 mg/kg bw. Ref. : 47 2.3.4. Sub-chronic 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 and other hair-dye constituents were mixed with an equal volume of 6 % hydrogen peroxide. A dose of 1","page":6,"pdf":"out156_en.pdf","row_type":"noael_study","study_id":"out156_en_noael_005"}
SCCNFP_vision_codex	NOAEL	=4	mg/kg bw	human	-	-	irritation	{"dose":"Thus the usage volume of 100 ml contains at maximum 2.0 % Highest penetration PA (\u0001g/cm2) = 4.47 \u0001g/cm2 Typical body weight of human = 60 kg Exposed area (scalp) = 700 cm2 Systemic exposure PA x 700 cm2 = 3.129 mg Systemic exposure dose (SED) PA x 700/ 60 x 1000 = 0.052 mg/kg bw No observed adverse effect level (mg/kg) NOAEL = 4 mg/kg bw (specie...","effect":"_______________________________________________________ 24 2.11. Safety evaluation CALCULATION OF THE MARGIN OF SAFETY (p-PHENYLENEDIAMINE) (Oxidative) The maximum concentration of 4.0 % of p-Phenylenediamine is mixed before use with H2O2. Thus the usage volume of 100 ml contains at maximum 2.0 % Highest penetration PA (\u0001g/cm2) = 4.47 \u0001g/cm2 Typical body weight of human = 60 kg Exposed area (scalp) = 700 cm2 Systemic exposure PA x 700 cm2 = 3.129 mg Systemic exposure dose (SED) PA x 700/ 60 x 1000 = 0.052 mg/kg bw No observed adverse effect level (mg/kg) NOAEL = 4 mg/kg bw (species, route of application) Margin of Safety : NOAEL / SED = 77 2.12. Conclusions PPD is used as an oxidising colouring agent for hair dyeing up to a maximum permitted concentration of 4% (free base) in the finished (marketed) cosmetic product. However, in combination with hydrogen peroxide, the maximum use concentration upon application is 2% (free base). * PPD was not irritant or corrosive for the skin and the eye when applied in a 2.5% aqueous solution. * PPD is a strong contact a","page":24,"pdf":"out156_en.pdf","row_type":"noael_study","study_id":"out156_en_noael_006"}
SCCNFP_vision_codex	NOAEL	=5	mg/kg bw/day	rat	oral	Sub-chronic	repeated dose toxicity	{"citation":"Ref. : 120 2","dose":"blood chemistry changes resulted in both sexes at dose level of 5 mg/kg/day or greater (increased lactate dehydrogenase and creatine phosphokinase levels). - 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 t...","effect":"blood chemistry changes resulted in both sexes at dose level of 5 mg/kg/day or greater (increased lactate dehydrogenase and creatine phosphokinase levels). - 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 NOAEL was \u0001 5 mg/kg bw/day. Ref. : 120 2.3.3. Sub-chronic 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 guideline N° 408 (1981). PPD was administered by gavage at corresponding dose levels of 2, 4, 8 and 16 mg/kg/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 twice daily for mortality/viability and once daily for clinical signs","page":5,"pdf":"out156_en.pdf","row_type":"noael_study","study_id":"out156_en_noael_001"}
SCCNFP_vision_codex	NOAEL	=4	mg/kg/day	rat	oral	12-week	NOAEL study	{"citation":"Ref. : 121 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","dose":"-related liver weights were significantly increased for males given 8 mg/kg/day and 16 mg/kg/day.","effect":"-related liver weights were significantly increased for males given 8 mg/kg/day and 16 mg/kg/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 NOAEL of PPD was established at 4 mg/kg/day. Ref. : 121 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/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 k","page":6,"pdf":"out156_en.pdf","row_type":"noael_study","study_id":"out156_en_noael_002"}
SCCNFP_vision_codex	NOAEL	=50	mg/kg bw	rat	oral	13-week	NOAEL study	{"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":"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/day respectively).","effect":"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/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. Fo","page":6,"pdf":"out156_en.pdf","row_type":"noael_study","study_id":"out156_en_noael_003"}
SCCNFP_vision_codex	NOAEL	=8	mg/kg	rabbit	dermal	13weeks	repeated dose toxicity	{"citation":"Ref. : 47 2","dose":"Food intake and body weight gain of treated group were similar to the controls.","effect":"y evaluations were conducted before and after 4, 8 and 13weeks of dosing according to a test battery consisting in motor activity and functional battery assessments. There were no mortalities or clinical signs considered related to the test article. Food intake and body weight gain of treated group were similar to the controls. Neuropathology evaluations did not reveal abnormalities within the nervous system or skeletal muscle. There was no effect of the test substance on ocular tissue. Based on these results, the NOEL was 8 mg/kg for both sexes and since the modifications observed can be assumed referring to pharmacological responses and not to neurotoxicity, the NOAEL was 16 mg/kg bw. Ref. : 47 2.3.4. Sub-chronic 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 and other hair-dye constituents were mixed with an equal volume of 6 % hydrogen peroxide. A dose of 1","page":6,"pdf":"out156_en.pdf","row_type":"noael_study","study_id":"out156_en_noael_004"}
SCCNFP_vision_codex	NOAEL	=16	mg/kg bw	rabbit	dermal	Sub-chronic	repeated dose toxicity	{"citation":"Ref. : 47 2","dose":"Food intake and body weight gain of treated group were similar to the controls.","effect":"assessments. There were no mortalities or clinical signs considered related to the test article. Food intake and body weight gain of treated group were similar to the controls. Neuropathology evaluations did not reveal abnormalities within the nervous system or skeletal muscle. There was no effect of the test substance on ocular tissue. Based on these results, the NOEL was 8 mg/kg for both sexes and since the modifications observed can be assumed referring to pharmacological responses and not to neurotoxicity, the NOAEL was 16 mg/kg bw. Ref. : 47 2.3.4. Sub-chronic 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 and other hair-dye constituents were mixed with an equal volume of 6 % hydrogen peroxide. A dose of 1","page":6,"pdf":"out156_en.pdf","row_type":"noael_study","study_id":"out156_en_noael_005"}
SCCNFP_vision_codex	NOAEL	=4	mg/kg bw	human	-	-	irritation	{"dose":"Thus the usage volume of 100 ml contains at maximum 2.0 % Highest penetration PA (\u0001g/cm2) = 4.47 \u0001g/cm2 Typical body weight of human = 60 kg Exposed area (scalp) = 700 cm2 Systemic exposure PA x 700 cm2 = 3.129 mg Systemic exposure dose (SED) PA x 700/ 60 x 1000 = 0.052 mg/kg bw No observed adverse effect level (mg/kg) NOAEL = 4 mg/kg bw (specie...","effect":"_______________________________________________________ 24 2.11. Safety evaluation CALCULATION OF THE MARGIN OF SAFETY (p-PHENYLENEDIAMINE) (Oxidative) The maximum concentration of 4.0 % of p-Phenylenediamine is mixed before use with H2O2. Thus the usage volume of 100 ml contains at maximum 2.0 % Highest penetration PA (\u0001g/cm2) = 4.47 \u0001g/cm2 Typical body weight of human = 60 kg Exposed area (scalp) = 700 cm2 Systemic exposure PA x 700 cm2 = 3.129 mg Systemic exposure dose (SED) PA x 700/ 60 x 1000 = 0.052 mg/kg bw No observed adverse effect level (mg/kg) NOAEL = 4 mg/kg bw (species, route of application) Margin of Safety : NOAEL / SED = 77 2.12. Conclusions PPD is used as an oxidising colouring agent for hair dyeing up to a maximum permitted concentration of 4% (free base) in the finished (marketed) cosmetic product. However, in combination with hydrogen peroxide, the maximum use concentration upon application is 2% (free base). * PPD was not irritant or corrosive for the skin and the eye when applied in a 2.5% aqueous solution. * PPD is a strong contact a","page":24,"pdf":"out156_en.pdf","row_type":"noael_study","study_id":"out156_en_noael_006"}
SCCNFP_vision_codex	NOAEL	=5	mg/kg bw/day	rat	oral	Sub-chronic	repeated dose toxicity	{"citation":"Ref. : 120 2","dose":"blood chemistry changes resulted in both sexes at dose level of 5 mg/kg/day or greater (increased lactate dehydrogenase and creatine phosphokinase levels). - 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 t...","effect":"blood chemistry changes resulted in both sexes at dose level of 5 mg/kg/day or greater (increased lactate dehydrogenase and creatine phosphokinase levels). - 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 NOAEL was \u0001 5 mg/kg bw/day. Ref. : 120 2.3.3. Sub-chronic 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 guideline N° 408 (1981). PPD was administered by gavage at corresponding dose levels of 2, 4, 8 and 16 mg/kg/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 twice daily for mortality/viability and once daily for clinical signs","page":5,"pdf":"out156_en.pdf","row_type":"noael_study","study_id":"out156_en_noael_001"}
SCCNFP_vision_codex	NOAEL	=4	mg/kg/day	rat	oral	12-week	NOAEL study	{"citation":"Ref. : 121 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","dose":"-related liver weights were significantly increased for males given 8 mg/kg/day and 16 mg/kg/day.","effect":"-related liver weights were significantly increased for males given 8 mg/kg/day and 16 mg/kg/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 NOAEL of PPD was established at 4 mg/kg/day. Ref. : 121 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/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 k","page":6,"pdf":"out156_en.pdf","row_type":"noael_study","study_id":"out156_en_noael_002"}
SCCNFP_vision_codex	NOAEL	=50	mg/kg bw	rat	oral	13-week	NOAEL study	{"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":"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/day respectively).","effect":"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/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. Fo","page":6,"pdf":"out156_en.pdf","row_type":"noael_study","study_id":"out156_en_noael_003"}
SCCNFP_vision_codex	NOAEL	=8	mg/kg	rabbit	dermal	13weeks	repeated dose toxicity	{"citation":"Ref. : 47 2","dose":"Food intake and body weight gain of treated group were similar to the controls.","effect":"y evaluations were conducted before and after 4, 8 and 13weeks of dosing according to a test battery consisting in motor activity and functional battery assessments. There were no mortalities or clinical signs considered related to the test article. Food intake and body weight gain of treated group were similar to the controls. Neuropathology evaluations did not reveal abnormalities within the nervous system or skeletal muscle. There was no effect of the test substance on ocular tissue. Based on these results, the NOEL was 8 mg/kg for both sexes and since the modifications observed can be assumed referring to pharmacological responses and not to neurotoxicity, the NOAEL was 16 mg/kg bw. Ref. : 47 2.3.4. Sub-chronic 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 and other hair-dye constituents were mixed with an equal volume of 6 % hydrogen peroxide. A dose of 1","page":6,"pdf":"out156_en.pdf","row_type":"noael_study","study_id":"out156_en_noael_004"}
SCCNFP_vision_codex	NOAEL	=16	mg/kg bw	rabbit	dermal	Sub-chronic	repeated dose toxicity	{"citation":"Ref. : 47 2","dose":"Food intake and body weight gain of treated group were similar to the controls.","effect":"assessments. There were no mortalities or clinical signs considered related to the test article. Food intake and body weight gain of treated group were similar to the controls. Neuropathology evaluations did not reveal abnormalities within the nervous system or skeletal muscle. There was no effect of the test substance on ocular tissue. Based on these results, the NOEL was 8 mg/kg for both sexes and since the modifications observed can be assumed referring to pharmacological responses and not to neurotoxicity, the NOAEL was 16 mg/kg bw. Ref. : 47 2.3.4. Sub-chronic 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 and other hair-dye constituents were mixed with an equal volume of 6 % hydrogen peroxide. A dose of 1","page":6,"pdf":"out156_en.pdf","row_type":"noael_study","study_id":"out156_en_noael_005"}
SCCNFP_vision_codex	NOAEL	=4	mg/kg bw	human	-	-	irritation	{"dose":"Thus the usage volume of 100 ml contains at maximum 2.0 % Highest penetration PA (\u0001g/cm2) = 4.47 \u0001g/cm2 Typical body weight of human = 60 kg Exposed area (scalp) = 700 cm2 Systemic exposure PA x 700 cm2 = 3.129 mg Systemic exposure dose (SED) PA x 700/ 60 x 1000 = 0.052 mg/kg bw No observed adverse effect level (mg/kg) NOAEL = 4 mg/kg bw (specie...","effect":"_______________________________________________________ 24 2.11. Safety evaluation CALCULATION OF THE MARGIN OF SAFETY (p-PHENYLENEDIAMINE) (Oxidative) The maximum concentration of 4.0 % of p-Phenylenediamine is mixed before use with H2O2. Thus the usage volume of 100 ml contains at maximum 2.0 % Highest penetration PA (\u0001g/cm2) = 4.47 \u0001g/cm2 Typical body weight of human = 60 kg Exposed area (scalp) = 700 cm2 Systemic exposure PA x 700 cm2 = 3.129 mg Systemic exposure dose (SED) PA x 700/ 60 x 1000 = 0.052 mg/kg bw No observed adverse effect level (mg/kg) NOAEL = 4 mg/kg bw (species, route of application) Margin of Safety : NOAEL / SED = 77 2.12. Conclusions PPD is used as an oxidising colouring agent for hair dyeing up to a maximum permitted concentration of 4% (free base) in the finished (marketed) cosmetic product. However, in combination with hydrogen peroxide, the maximum use concentration upon application is 2% (free base). * PPD was not irritant or corrosive for the skin and the eye when applied in a 2.5% aqueous solution. * PPD is a strong contact a","page":24,"pdf":"out156_en.pdf","row_type":"noael_study","study_id":"out156_en_noael_006"}
SCCNFP_vision_codex	NOAEL	=5	mg/kg bw/day	rat	oral	Sub-chronic	repeated dose toxicity	{"citation":"Ref. : 120 2","dose":"blood chemistry changes resulted in both sexes at dose level of 5 mg/kg/day or greater (increased lactate dehydrogenase and creatine phosphokinase levels). - 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 t...","effect":"blood chemistry changes resulted in both sexes at dose level of 5 mg/kg/day or greater (increased lactate dehydrogenase and creatine phosphokinase levels). - 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 NOAEL was \u0001 5 mg/kg bw/day. Ref. : 120 2.3.3. Sub-chronic 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 guideline N° 408 (1981). PPD was administered by gavage at corresponding dose levels of 2, 4, 8 and 16 mg/kg/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 twice daily for mortality/viability and once daily for clinical signs","page":5,"pdf":"out156_en.pdf","row_type":"noael_study","study_id":"out156_en_noael_001"}
SCCNFP_vision_codex	NOAEL	=4	mg/kg/day	rat	oral	12-week	NOAEL study	{"citation":"Ref. : 121 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","dose":"-related liver weights were significantly increased for males given 8 mg/kg/day and 16 mg/kg/day.","effect":"-related liver weights were significantly increased for males given 8 mg/kg/day and 16 mg/kg/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 NOAEL of PPD was established at 4 mg/kg/day. Ref. : 121 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/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 k","page":6,"pdf":"out156_en.pdf","row_type":"noael_study","study_id":"out156_en_noael_002"}
SCCNFP_vision_codex	NOAEL	=50	mg/kg bw	rat	oral	13-week	NOAEL study	{"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":"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/day respectively).","effect":"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/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. Fo","page":6,"pdf":"out156_en.pdf","row_type":"noael_study","study_id":"out156_en_noael_003"}
SCCNFP_vision_codex	NOAEL	=8	mg/kg	rabbit	dermal	13weeks	repeated dose toxicity	{"citation":"Ref. : 47 2","dose":"Food intake and body weight gain of treated group were similar to the controls.","effect":"y evaluations were conducted before and after 4, 8 and 13weeks of dosing according to a test battery consisting in motor activity and functional battery assessments. There were no mortalities or clinical signs considered related to the test article. Food intake and body weight gain of treated group were similar to the controls. Neuropathology evaluations did not reveal abnormalities within the nervous system or skeletal muscle. There was no effect of the test substance on ocular tissue. Based on these results, the NOEL was 8 mg/kg for both sexes and since the modifications observed can be assumed referring to pharmacological responses and not to neurotoxicity, the NOAEL was 16 mg/kg bw. Ref. : 47 2.3.4. Sub-chronic 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 and other hair-dye constituents were mixed with an equal volume of 6 % hydrogen peroxide. A dose of 1","page":6,"pdf":"out156_en.pdf","row_type":"noael_study","study_id":"out156_en_noael_004"}
SCCNFP_vision_codex	NOAEL	=16	mg/kg bw	rabbit	dermal	Sub-chronic	repeated dose toxicity	{"citation":"Ref. : 47 2","dose":"Food intake and body weight gain of treated group were similar to the controls.","effect":"assessments. There were no mortalities or clinical signs considered related to the test article. Food intake and body weight gain of treated group were similar to the controls. Neuropathology evaluations did not reveal abnormalities within the nervous system or skeletal muscle. There was no effect of the test substance on ocular tissue. Based on these results, the NOEL was 8 mg/kg for both sexes and since the modifications observed can be assumed referring to pharmacological responses and not to neurotoxicity, the NOAEL was 16 mg/kg bw. Ref. : 47 2.3.4. Sub-chronic 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 and other hair-dye constituents were mixed with an equal volume of 6 % hydrogen peroxide. A dose of 1","page":6,"pdf":"out156_en.pdf","row_type":"noael_study","study_id":"out156_en_noael_005"}
SCCNFP_vision_codex	NOAEL	=4	mg/kg bw	human	-	-	irritation	{"dose":"Thus the usage volume of 100 ml contains at maximum 2.0 % Highest penetration PA (\u0001g/cm2) = 4.47 \u0001g/cm2 Typical body weight of human = 60 kg Exposed area (scalp) = 700 cm2 Systemic exposure PA x 700 cm2 = 3.129 mg Systemic exposure dose (SED) PA x 700/ 60 x 1000 = 0.052 mg/kg bw No observed adverse effect level (mg/kg) NOAEL = 4 mg/kg bw (specie...","effect":"_______________________________________________________ 24 2.11. Safety evaluation CALCULATION OF THE MARGIN OF SAFETY (p-PHENYLENEDIAMINE) (Oxidative) The maximum concentration of 4.0 % of p-Phenylenediamine is mixed before use with H2O2. Thus the usage volume of 100 ml contains at maximum 2.0 % Highest penetration PA (\u0001g/cm2) = 4.47 \u0001g/cm2 Typical body weight of human = 60 kg Exposed area (scalp) = 700 cm2 Systemic exposure PA x 700 cm2 = 3.129 mg Systemic exposure dose (SED) PA x 700/ 60 x 1000 = 0.052 mg/kg bw No observed adverse effect level (mg/kg) NOAEL = 4 mg/kg bw (species, route of application) Margin of Safety : NOAEL / SED = 77 2.12. Conclusions PPD is used as an oxidising colouring agent for hair dyeing up to a maximum permitted concentration of 4% (free base) in the finished (marketed) cosmetic product. However, in combination with hydrogen peroxide, the maximum use concentration upon application is 2% (free base). * PPD was not irritant or corrosive for the skin and the eye when applied in a 2.5% aqueous solution. * PPD is a strong contact a","page":24,"pdf":"out156_en.pdf","row_type":"noael_study","study_id":"out156_en_noael_006"}

SCCS_vision_codex 108 endpoints

Source	Endpoint Type	Value	Unit	Species	Route	Duration	Study Type	Reference
SCCS_vision_codex	NOAEL	<5	mg/kg bw/day	-	-	-	NOAEL study	{"citation":"Ref.: 120","dose":"blood chemistry changes resulted in both sexes at dose level of 5 mg/kg/day or greater (increased lactate dehydrogenase and creatine phosphokinase levels). - 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 t...","effect":"blood chemistry changes resulted in both sexes at dose level of 5 mg/kg/day or greater (increased lactate dehydrogenase and creatine phosphokinase levels). - 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 NOAEL was < 5 mg/kg bw/day. Ref.: 120","page":13,"pdf":"sccp_o_069.pdf","row_type":"noael_study","study_id":"sccp_o_069_noael_001"}
SCCS_vision_codex	NOAEL	=16	mg/kg bw	rat	oral	12-week	NOAEL study	{"citation":"Ref.: 121 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","dose":"-related liver weights were significantly increased for males given 8 mg/kg/day and 16 mg/kg/day.","effect":"-related liver weights were significantly increased for males given 8 mg/kg/day and 16 mg/kg/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 NOAEL of PPD was established at 4 mg/kg/day. Ref.: 121 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/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","page":14,"pdf":"sccp_o_069.pdf","row_type":"noael_study","study_id":"sccp_o_069_noael_002"}
SCCS_vision_codex	NOAEL	=50	mg/kg bw	rat	oral	-	NOAEL study	{"citation":"Ref.: 53","dose":"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/day respectively).","effect":"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/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","page":14,"pdf":"sccp_o_069.pdf","row_type":"noael_study","study_id":"sccp_o_069_noael_003"}
SCCS_vision_codex	NOAEL	=8	mg/kg	rabbit	dermal	90 day	NOAEL study	{"citation":"Ref.: 46 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.","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 for both sexes, the NOAEL was 16 mg/kg bw. Ref.: 46 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 and other hair-dye constituents were mixed with an equal volume of 6% hydrogen peroxide. A dose of 1 ml/kg of this mixture was applied for 1 hour without occlusion to three application sites on six animals of each sex. The application sites were abraded pri","page":15,"pdf":"sccp_o_069.pdf","row_type":"noael_study","study_id":"sccp_o_069_noael_004"}
SCCS_vision_codex	NOAEL	=5	mg/kg bw	human	-	developmental	developmental toxicity	{"citation":"Ref.: 8, subm","dose":"SCCP/0989/06 Opinion on p-phenylenediamine ____________________________________________________________________________________________ 46 The NOAEL of maternal toxicity is 5 mg/kg bw whereas the NOAEL of developmental toxicity is 10 mg/kg bw.","effect":"SCCP/0989/06 Opinion on p-phenylenediamine ____________________________________________________________________________________________ 46 The NOAEL of maternal toxicity is 5 mg/kg bw whereas the NOAEL of developmental toxicity is 10 mg/kg bw. Ref.: 8, subm. 12/2005 3.3.9. Toxicokinetics Human hepatic metabolism in vitro Guideline: / Cells: human hepatocytes, 4 male donors (cryo-preserved) Test substance: p-phenylenediamine dihydrochloride Sigma-Aldrich P6001 Radiolabeled substance: [14C(u)]-1,4-phenylenediamine dihydrochloride (14C PPD) Specific activity: 33.2 mCi/mmol Batch: Lot No. 10194-57-A Purity: > 98% Test system A hepatocytes (10 µM, 50 µM and 100","page":46,"pdf":"sccp_o_069.pdf","row_type":"noael_study","study_id":"sccp_o_069_noael_006"}
SCCS_vision_codex	NOAEL	=0.052	mg/kg bw	rat	oral	subchronic	repeated dose toxicity	{"dose":"Thus the usage volume of 100 ml contains at maximum 2.0% Highest penetration PA (µg/cm2) = 4.47 µg/cm2 Typical body weight of human = 60 kg Exposed area (scalp) = 700 cm2 Systemic exposure PA x 700 cm2 = 3.129 mg Systemic exposure dose (SED) PA x 700/ 60 x 1000 = 0.052 mg/kg bw No observed adverse effect level (mg/kg) NOAEL = 4 mg/kg bw (rat, or...","effect":"(including calculation of the MoS) Taken from SCCNFP/0129/99, adopted in 2002 CALCULATION OF THE MARGIN OF SAFETY (p-PHENYLENEDIAMINE) (Oxidative) The maximum concentration of 4.0% of p-Phenylenediamine is mixed before use with H2O2. Thus the usage volume of 100 ml contains at maximum 2.0% Highest penetration PA (µg/cm2) = 4.47 µg/cm2 Typical body weight of human = 60 kg Exposed area (scalp) = 700 cm2 Systemic exposure PA x 700 cm2 = 3.129 mg Systemic exposure dose (SED) PA x 700/ 60 x 1000 = 0.052 mg/kg bw No observed adverse effect level (mg/kg) NOAEL = 4 mg/kg bw (rat, oral, subchronic toxicity) Margin of Safety NOAEL / SED = 77","page":52,"pdf":"sccp_o_069.pdf","row_type":"noael_study","study_id":"sccp_o_069_noael_007"}
SCCS_vision_codex	NOAEL	=4	mg/kg bw	rat	oral	subchronic	repeated dose toxicity	{"dose":"Thus the usage volume of 100 ml contains at maximum 2.0% Highest penetration PA (µg/cm2) = 4.47 µg/cm2 Typical body weight of human = 60 kg Exposed area (scalp) = 700 cm2 Systemic exposure PA x 700 cm2 = 3.129 mg Systemic exposure dose (SED) PA x 700/ 60 x 1000 = 0.052 mg/kg bw No observed adverse effect level (mg/kg) NOAEL = 4 mg/kg bw (rat, or...","effect":"n from SCCNFP/0129/99, adopted in 2002 CALCULATION OF THE MARGIN OF SAFETY (p-PHENYLENEDIAMINE) (Oxidative) The maximum concentration of 4.0% of p-Phenylenediamine is mixed before use with H2O2. Thus the usage volume of 100 ml contains at maximum 2.0% Highest penetration PA (µg/cm2) = 4.47 µg/cm2 Typical body weight of human = 60 kg Exposed area (scalp) = 700 cm2 Systemic exposure PA x 700 cm2 = 3.129 mg Systemic exposure dose (SED) PA x 700/ 60 x 1000 = 0.052 mg/kg bw No observed adverse effect level (mg/kg) NOAEL = 4 mg/kg bw (rat, oral, subchronic toxicity) Margin of Safety NOAEL / SED = 77","page":52,"pdf":"sccp_o_069.pdf","row_type":"noael_study","study_id":"sccp_o_069_noael_008"}
SCCS_vision_codex	NOAEL	=4	mg/kg	rat	oral	90-day	NOAEL study	{"dose":"SCCP/0989/06 Opinion on p-phenylenediamine ____________________________________________________________________________________________ 53 Safety evaluation based on toxicokinetics (taken from dossier) 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/...","effect":"SCCP/0989/06 Opinion on p-phenylenediamine ____________________________________________________________________________________________ 53 Safety evaluation based on toxicokinetics (taken from dossier) 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) 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 i","page":53,"pdf":"sccp_o_069.pdf","row_type":"noael_study","study_id":"sccp_o_069_noael_010"}
SCCS_vision_codex	NOAEL	=2	%	rat	-	-	NOAEL study	{"citation":"(Reference 14)","dose":"Taking into account that the human study was performed under maximal exposure conditions, such as maximal PPD concentration (2.0%), short hair length (2 cm) of the treated subjects and","effect":"ifferences for toxicokinetics and toxicodynamics (Reference 14). Therefore, the AUC-based margin of safety for PPD is sufficiently high to conclude that the human systemic exposure from hair dyeing with a dark-shade, PPD-containing oxidative hair dye poses no risk to human health. This view is further supported by the margin of safety on the basis of human and rat Cmax values (45-fold), which gives additional assurance that human systemic exposure from PPD-containing hair dyes is far lower than that in rats at the NOAEL. Taking into account that the human study was performed under maximal exposure conditions, such as maximal PPD concentration (2.0%), short hair length (2 cm) of the treated subjects and","page":53,"pdf":"sccp_o_069.pdf","row_type":"noael_study","study_id":"sccp_o_069_noael_012"}
SCCS_vision_codex	NOAEL	=4	mg/kg bw	rat	-	-	carcinogenicity	{"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","page":5,"pdf":"sccs_o_094.pdf","row_type":"noael_study","study_id":"sccs_o_094_noael_001"}
SCCS_vision_codex	NOAEL	<5	mg/kg bw/day	rat	oral	Sub-chronic	repeated dose toxicity	{"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...","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","page":16,"pdf":"sccs_o_094.pdf","row_type":"noael_study","study_id":"sccs_o_094_noael_002"}
SCCS_vision_codex	NOAEL	=16	mg/kg bw	-	-	-	NOAEL study	{"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.","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","page":16,"pdf":"sccs_o_094.pdf","row_type":"noael_study","study_id":"sccs_o_094_noael_003"}
SCCS_vision_codex	NOAEL	=4	mg/kg bw/day	-	-	-	NOAEL study	{"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.","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","page":16,"pdf":"sccs_o_094.pdf","row_type":"noael_study","study_id":"sccs_o_094_noael_004"}
SCCS_vision_codex	NOAEL	=8	mg/kg bw	rat	oral	3 days	NOAEL study	{"citation":"(Ref. 120)","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","page":17,"pdf":"sccs_o_094.pdf","row_type":"noael_study","study_id":"sccs_o_094_noael_008"}
SCCS_vision_codex	NOAEL	=50	mg/kg bw	rat	oral	13-week	NOAEL study	{"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).","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","page":17,"pdf":"sccs_o_094.pdf","row_type":"noael_study","study_id":"sccs_o_094_noael_009"}
SCCS_vision_codex	NOAEL	=8	mg/kg bw/d	rabbit	dermal	90 day	NOAEL study	{"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.","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","page":17,"pdf":"sccs_o_094.pdf","row_type":"noael_study","study_id":"sccs_o_094_noael_010"}
SCCS_vision_codex	NOAEL	=16	mg/kg bw/d	rabbit	dermal	90 day	NOAEL study	{"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.","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","page":17,"pdf":"sccs_o_094.pdf","row_type":"noael_study","study_id":"sccs_o_094_noael_011"}
SCCS_vision_codex	NOAEL	=14	-	rat	-	-	NOAEL study	{"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","page":58,"pdf":"sccs_o_094.pdf","row_type":"noael_study","study_id":"sccs_o_094_noael_014"}
SCCS_vision_codex	NOAEL	=4	mg/kg bw/d	-	oral	90 days	NOAEL study	{"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_vision_codex	NOAEL	=0.04	mg/kg bw/d	rat	oral	subchronic	repeated dose toxicity	{"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","page":59,"pdf":"sccs_o_094.pdf","row_type":"noael_study","study_id":"sccs_o_094_noael_022"}
SCCS_vision_codex	NOAEL	=1	%	rat	oral	-	NOAEL study	{"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.","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","page":61,"pdf":"sccs_o_094.pdf","row_type":"noael_study","study_id":"sccs_o_094_noael_027"}
SCCS_vision_codex	NOAEL	=6.45	mg/kg bw	rat	oral	-	NOAEL study	{"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","page":61,"pdf":"sccs_o_094.pdf","row_type":"noael_study","study_id":"sccs_o_094_noael_029"}
SCCS_vision_codex	NOAEL	=8	mg/kg bw/day	rat	-	-	NOAEL study	{"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","page":66,"pdf":"sccs_o_094.pdf","row_type":"noael_study","study_id":"sccs_o_094_noael_047"}
SCCS_vision_codex	NOAEL	=61	-	-	oral	-	NOAEL study	{"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","page":61,"pdf":"sccs_o_094.pdf","row_type":"noael_study","study_id":"sccs_o_094_noael_048"}
SCCS_vision_codex	NOAEL	=8	-	-	oral	-	NOAEL study	{"effect":"Unlabeled table on page 61: Gavage NOAEL of 8 \| 22152 \| 1415 \| 15.6 \| 966 \| 22.2","page":61,"pdf":"sccs_o_094.pdf","row_type":"noael_study","study_id":"sccs_o_094_noael_057"}
SCCS_vision_codex	NOAEL	=16	-	-	oral	-	NOAEL study	{"effect":"Unlabeled table on page 61: Gavage NOAEL of 16 \| 44304 \| 1415 \| 31.3 \| 966 \| 45.9","page":61,"pdf":"sccs_o_094.pdf","row_type":"noael_study","study_id":"sccs_o_094_noael_058"}
SCCS_vision_codex	NOAEL	=50	-	-	oral	-	NOAEL study	{"effect":"Unlabeled table on page 61: Dietary NOEL of 50 \| 138450 \| 1415 \| 97.8 \| 966 \| 143.3","page":61,"pdf":"sccs_o_094.pdf","row_type":"noael_study","study_id":"sccs_o_094_noael_059"}
SCCS_vision_codex	NOAEL	<5	mg/kg bw/day	-	-	-	NOAEL study	{"citation":"Ref.: 120","dose":"blood chemistry changes resulted in both sexes at dose level of 5 mg/kg/day or greater (increased lactate dehydrogenase and creatine phosphokinase levels). - 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 t...","effect":"blood chemistry changes resulted in both sexes at dose level of 5 mg/kg/day or greater (increased lactate dehydrogenase and creatine phosphokinase levels). - 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 NOAEL was < 5 mg/kg bw/day. Ref.: 120","page":13,"pdf":"sccp_o_069.pdf","row_type":"noael_study","study_id":"sccp_o_069_noael_001"}
SCCS_vision_codex	NOAEL	=16	mg/kg bw	rat	oral	12-week	NOAEL study	{"citation":"Ref.: 121 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","dose":"-related liver weights were significantly increased for males given 8 mg/kg/day and 16 mg/kg/day.","effect":"-related liver weights were significantly increased for males given 8 mg/kg/day and 16 mg/kg/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 NOAEL of PPD was established at 4 mg/kg/day. Ref.: 121 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/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","page":14,"pdf":"sccp_o_069.pdf","row_type":"noael_study","study_id":"sccp_o_069_noael_002"}
SCCS_vision_codex	NOAEL	=50	mg/kg bw	rat	oral	-	NOAEL study	{"citation":"Ref.: 53","dose":"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/day respectively).","effect":"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/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","page":14,"pdf":"sccp_o_069.pdf","row_type":"noael_study","study_id":"sccp_o_069_noael_003"}
SCCS_vision_codex	NOAEL	=8	mg/kg	rabbit	dermal	90 day	NOAEL study	{"citation":"Ref.: 46 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.","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 for both sexes, the NOAEL was 16 mg/kg bw. Ref.: 46 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 and other hair-dye constituents were mixed with an equal volume of 6% hydrogen peroxide. A dose of 1 ml/kg of this mixture was applied for 1 hour without occlusion to three application sites on six animals of each sex. The application sites were abraded pri","page":15,"pdf":"sccp_o_069.pdf","row_type":"noael_study","study_id":"sccp_o_069_noael_004"}
SCCS_vision_codex	NOAEL	=5	mg/kg bw	human	-	developmental	developmental toxicity	{"citation":"Ref.: 8, subm","dose":"SCCP/0989/06 Opinion on p-phenylenediamine ____________________________________________________________________________________________ 46 The NOAEL of maternal toxicity is 5 mg/kg bw whereas the NOAEL of developmental toxicity is 10 mg/kg bw.","effect":"SCCP/0989/06 Opinion on p-phenylenediamine ____________________________________________________________________________________________ 46 The NOAEL of maternal toxicity is 5 mg/kg bw whereas the NOAEL of developmental toxicity is 10 mg/kg bw. Ref.: 8, subm. 12/2005 3.3.9. Toxicokinetics Human hepatic metabolism in vitro Guideline: / Cells: human hepatocytes, 4 male donors (cryo-preserved) Test substance: p-phenylenediamine dihydrochloride Sigma-Aldrich P6001 Radiolabeled substance: [14C(u)]-1,4-phenylenediamine dihydrochloride (14C PPD) Specific activity: 33.2 mCi/mmol Batch: Lot No. 10194-57-A Purity: > 98% Test system A hepatocytes (10 µM, 50 µM and 100","page":46,"pdf":"sccp_o_069.pdf","row_type":"noael_study","study_id":"sccp_o_069_noael_006"}
SCCS_vision_codex	NOAEL	=0.052	mg/kg bw	rat	oral	subchronic	repeated dose toxicity	{"dose":"Thus the usage volume of 100 ml contains at maximum 2.0% Highest penetration PA (µg/cm2) = 4.47 µg/cm2 Typical body weight of human = 60 kg Exposed area (scalp) = 700 cm2 Systemic exposure PA x 700 cm2 = 3.129 mg Systemic exposure dose (SED) PA x 700/ 60 x 1000 = 0.052 mg/kg bw No observed adverse effect level (mg/kg) NOAEL = 4 mg/kg bw (rat, or...","effect":"(including calculation of the MoS) Taken from SCCNFP/0129/99, adopted in 2002 CALCULATION OF THE MARGIN OF SAFETY (p-PHENYLENEDIAMINE) (Oxidative) The maximum concentration of 4.0% of p-Phenylenediamine is mixed before use with H2O2. Thus the usage volume of 100 ml contains at maximum 2.0% Highest penetration PA (µg/cm2) = 4.47 µg/cm2 Typical body weight of human = 60 kg Exposed area (scalp) = 700 cm2 Systemic exposure PA x 700 cm2 = 3.129 mg Systemic exposure dose (SED) PA x 700/ 60 x 1000 = 0.052 mg/kg bw No observed adverse effect level (mg/kg) NOAEL = 4 mg/kg bw (rat, oral, subchronic toxicity) Margin of Safety NOAEL / SED = 77","page":52,"pdf":"sccp_o_069.pdf","row_type":"noael_study","study_id":"sccp_o_069_noael_007"}
SCCS_vision_codex	NOAEL	=4	mg/kg bw	rat	oral	subchronic	repeated dose toxicity	{"dose":"Thus the usage volume of 100 ml contains at maximum 2.0% Highest penetration PA (µg/cm2) = 4.47 µg/cm2 Typical body weight of human = 60 kg Exposed area (scalp) = 700 cm2 Systemic exposure PA x 700 cm2 = 3.129 mg Systemic exposure dose (SED) PA x 700/ 60 x 1000 = 0.052 mg/kg bw No observed adverse effect level (mg/kg) NOAEL = 4 mg/kg bw (rat, or...","effect":"n from SCCNFP/0129/99, adopted in 2002 CALCULATION OF THE MARGIN OF SAFETY (p-PHENYLENEDIAMINE) (Oxidative) The maximum concentration of 4.0% of p-Phenylenediamine is mixed before use with H2O2. Thus the usage volume of 100 ml contains at maximum 2.0% Highest penetration PA (µg/cm2) = 4.47 µg/cm2 Typical body weight of human = 60 kg Exposed area (scalp) = 700 cm2 Systemic exposure PA x 700 cm2 = 3.129 mg Systemic exposure dose (SED) PA x 700/ 60 x 1000 = 0.052 mg/kg bw No observed adverse effect level (mg/kg) NOAEL = 4 mg/kg bw (rat, oral, subchronic toxicity) Margin of Safety NOAEL / SED = 77","page":52,"pdf":"sccp_o_069.pdf","row_type":"noael_study","study_id":"sccp_o_069_noael_008"}
SCCS_vision_codex	NOAEL	=4	mg/kg	rat	oral	90-day	NOAEL study	{"dose":"SCCP/0989/06 Opinion on p-phenylenediamine ____________________________________________________________________________________________ 53 Safety evaluation based on toxicokinetics (taken from dossier) 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/...","effect":"SCCP/0989/06 Opinion on p-phenylenediamine ____________________________________________________________________________________________ 53 Safety evaluation based on toxicokinetics (taken from dossier) 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) 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 i","page":53,"pdf":"sccp_o_069.pdf","row_type":"noael_study","study_id":"sccp_o_069_noael_010"}
SCCS_vision_codex	NOAEL	=2	%	rat	-	-	NOAEL study	{"citation":"(Reference 14)","dose":"Taking into account that the human study was performed under maximal exposure conditions, such as maximal PPD concentration (2.0%), short hair length (2 cm) of the treated subjects and","effect":"ifferences for toxicokinetics and toxicodynamics (Reference 14). Therefore, the AUC-based margin of safety for PPD is sufficiently high to conclude that the human systemic exposure from hair dyeing with a dark-shade, PPD-containing oxidative hair dye poses no risk to human health. This view is further supported by the margin of safety on the basis of human and rat Cmax values (45-fold), which gives additional assurance that human systemic exposure from PPD-containing hair dyes is far lower than that in rats at the NOAEL. Taking into account that the human study was performed under maximal exposure conditions, such as maximal PPD concentration (2.0%), short hair length (2 cm) of the treated subjects and","page":53,"pdf":"sccp_o_069.pdf","row_type":"noael_study","study_id":"sccp_o_069_noael_012"}
SCCS_vision_codex	NOAEL	<5	mg/kg bw/day	-	-	-	NOAEL study	{"citation":"Ref.: 120","dose":"blood chemistry changes resulted in both sexes at dose level of 5 mg/kg/day or greater (increased lactate dehydrogenase and creatine phosphokinase levels). - 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 t...","effect":"blood chemistry changes resulted in both sexes at dose level of 5 mg/kg/day or greater (increased lactate dehydrogenase and creatine phosphokinase levels). - 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 NOAEL was < 5 mg/kg bw/day. Ref.: 120","page":13,"pdf":"sccp_o_069.pdf","row_type":"noael_study","study_id":"sccp_o_069_noael_001"}
SCCS_vision_codex	NOAEL	=16	mg/kg bw	rat	oral	12-week	NOAEL study	{"citation":"Ref.: 121 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","dose":"-related liver weights were significantly increased for males given 8 mg/kg/day and 16 mg/kg/day.","effect":"-related liver weights were significantly increased for males given 8 mg/kg/day and 16 mg/kg/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 NOAEL of PPD was established at 4 mg/kg/day. Ref.: 121 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/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","page":14,"pdf":"sccp_o_069.pdf","row_type":"noael_study","study_id":"sccp_o_069_noael_002"}
SCCS_vision_codex	NOAEL	=50	mg/kg bw	rat	oral	-	NOAEL study	{"citation":"Ref.: 53","dose":"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/day respectively).","effect":"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/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","page":14,"pdf":"sccp_o_069.pdf","row_type":"noael_study","study_id":"sccp_o_069_noael_003"}
SCCS_vision_codex	NOAEL	=8	mg/kg	rabbit	dermal	90 day	NOAEL study	{"citation":"Ref.: 46 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.","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 for both sexes, the NOAEL was 16 mg/kg bw. Ref.: 46 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 and other hair-dye constituents were mixed with an equal volume of 6% hydrogen peroxide. A dose of 1 ml/kg of this mixture was applied for 1 hour without occlusion to three application sites on six animals of each sex. The application sites were abraded pri","page":15,"pdf":"sccp_o_069.pdf","row_type":"noael_study","study_id":"sccp_o_069_noael_004"}
SCCS_vision_codex	NOAEL	=5	mg/kg bw	human	-	developmental	developmental toxicity	{"citation":"Ref.: 8, subm","dose":"SCCP/0989/06 Opinion on p-phenylenediamine ____________________________________________________________________________________________ 46 The NOAEL of maternal toxicity is 5 mg/kg bw whereas the NOAEL of developmental toxicity is 10 mg/kg bw.","effect":"SCCP/0989/06 Opinion on p-phenylenediamine ____________________________________________________________________________________________ 46 The NOAEL of maternal toxicity is 5 mg/kg bw whereas the NOAEL of developmental toxicity is 10 mg/kg bw. Ref.: 8, subm. 12/2005 3.3.9. Toxicokinetics Human hepatic metabolism in vitro Guideline: / Cells: human hepatocytes, 4 male donors (cryo-preserved) Test substance: p-phenylenediamine dihydrochloride Sigma-Aldrich P6001 Radiolabeled substance: [14C(u)]-1,4-phenylenediamine dihydrochloride (14C PPD) Specific activity: 33.2 mCi/mmol Batch: Lot No. 10194-57-A Purity: > 98% Test system A hepatocytes (10 µM, 50 µM and 100","page":46,"pdf":"sccp_o_069.pdf","row_type":"noael_study","study_id":"sccp_o_069_noael_006"}
SCCS_vision_codex	NOAEL	=0.052	mg/kg bw	rat	oral	subchronic	repeated dose toxicity	{"dose":"Thus the usage volume of 100 ml contains at maximum 2.0% Highest penetration PA (µg/cm2) = 4.47 µg/cm2 Typical body weight of human = 60 kg Exposed area (scalp) = 700 cm2 Systemic exposure PA x 700 cm2 = 3.129 mg Systemic exposure dose (SED) PA x 700/ 60 x 1000 = 0.052 mg/kg bw No observed adverse effect level (mg/kg) NOAEL = 4 mg/kg bw (rat, or...","effect":"(including calculation of the MoS) Taken from SCCNFP/0129/99, adopted in 2002 CALCULATION OF THE MARGIN OF SAFETY (p-PHENYLENEDIAMINE) (Oxidative) The maximum concentration of 4.0% of p-Phenylenediamine is mixed before use with H2O2. Thus the usage volume of 100 ml contains at maximum 2.0% Highest penetration PA (µg/cm2) = 4.47 µg/cm2 Typical body weight of human = 60 kg Exposed area (scalp) = 700 cm2 Systemic exposure PA x 700 cm2 = 3.129 mg Systemic exposure dose (SED) PA x 700/ 60 x 1000 = 0.052 mg/kg bw No observed adverse effect level (mg/kg) NOAEL = 4 mg/kg bw (rat, oral, subchronic toxicity) Margin of Safety NOAEL / SED = 77","page":52,"pdf":"sccp_o_069.pdf","row_type":"noael_study","study_id":"sccp_o_069_noael_007"}
SCCS_vision_codex	NOAEL	=4	mg/kg bw	rat	oral	subchronic	repeated dose toxicity	{"dose":"Thus the usage volume of 100 ml contains at maximum 2.0% Highest penetration PA (µg/cm2) = 4.47 µg/cm2 Typical body weight of human = 60 kg Exposed area (scalp) = 700 cm2 Systemic exposure PA x 700 cm2 = 3.129 mg Systemic exposure dose (SED) PA x 700/ 60 x 1000 = 0.052 mg/kg bw No observed adverse effect level (mg/kg) NOAEL = 4 mg/kg bw (rat, or...","effect":"n from SCCNFP/0129/99, adopted in 2002 CALCULATION OF THE MARGIN OF SAFETY (p-PHENYLENEDIAMINE) (Oxidative) The maximum concentration of 4.0% of p-Phenylenediamine is mixed before use with H2O2. Thus the usage volume of 100 ml contains at maximum 2.0% Highest penetration PA (µg/cm2) = 4.47 µg/cm2 Typical body weight of human = 60 kg Exposed area (scalp) = 700 cm2 Systemic exposure PA x 700 cm2 = 3.129 mg Systemic exposure dose (SED) PA x 700/ 60 x 1000 = 0.052 mg/kg bw No observed adverse effect level (mg/kg) NOAEL = 4 mg/kg bw (rat, oral, subchronic toxicity) Margin of Safety NOAEL / SED = 77","page":52,"pdf":"sccp_o_069.pdf","row_type":"noael_study","study_id":"sccp_o_069_noael_008"}
SCCS_vision_codex	NOAEL	=4	mg/kg	rat	oral	90-day	NOAEL study	{"dose":"SCCP/0989/06 Opinion on p-phenylenediamine ____________________________________________________________________________________________ 53 Safety evaluation based on toxicokinetics (taken from dossier) 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/...","effect":"SCCP/0989/06 Opinion on p-phenylenediamine ____________________________________________________________________________________________ 53 Safety evaluation based on toxicokinetics (taken from dossier) 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) 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 i","page":53,"pdf":"sccp_o_069.pdf","row_type":"noael_study","study_id":"sccp_o_069_noael_010"}
SCCS_vision_codex	NOAEL	=2	%	rat	-	-	NOAEL study	{"citation":"(Reference 14)","dose":"Taking into account that the human study was performed under maximal exposure conditions, such as maximal PPD concentration (2.0%), short hair length (2 cm) of the treated subjects and","effect":"ifferences for toxicokinetics and toxicodynamics (Reference 14). Therefore, the AUC-based margin of safety for PPD is sufficiently high to conclude that the human systemic exposure from hair dyeing with a dark-shade, PPD-containing oxidative hair dye poses no risk to human health. This view is further supported by the margin of safety on the basis of human and rat Cmax values (45-fold), which gives additional assurance that human systemic exposure from PPD-containing hair dyes is far lower than that in rats at the NOAEL. Taking into account that the human study was performed under maximal exposure conditions, such as maximal PPD concentration (2.0%), short hair length (2 cm) of the treated subjects and","page":53,"pdf":"sccp_o_069.pdf","row_type":"noael_study","study_id":"sccp_o_069_noael_012"}
SCCS_vision_codex	NOAEL	=4	mg/kg bw	rat	-	-	carcinogenicity	{"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","page":5,"pdf":"sccs_o_094.pdf","row_type":"noael_study","study_id":"sccs_o_094_noael_001"}
SCCS_vision_codex	NOAEL	<5	mg/kg bw/day	rat	oral	Sub-chronic	repeated dose toxicity	{"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...","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","page":16,"pdf":"sccs_o_094.pdf","row_type":"noael_study","study_id":"sccs_o_094_noael_002"}
SCCS_vision_codex	NOAEL	=16	mg/kg bw	-	-	-	NOAEL study	{"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.","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","page":16,"pdf":"sccs_o_094.pdf","row_type":"noael_study","study_id":"sccs_o_094_noael_003"}
SCCS_vision_codex	NOAEL	=4	mg/kg bw/day	-	-	-	NOAEL study	{"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.","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","page":16,"pdf":"sccs_o_094.pdf","row_type":"noael_study","study_id":"sccs_o_094_noael_004"}
SCCS_vision_codex	NOAEL	=8	mg/kg bw	rat	oral	3 days	NOAEL study	{"citation":"(Ref. 120)","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","page":17,"pdf":"sccs_o_094.pdf","row_type":"noael_study","study_id":"sccs_o_094_noael_008"}
SCCS_vision_codex	NOAEL	=50	mg/kg bw	rat	oral	13-week	NOAEL study	{"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).","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","page":17,"pdf":"sccs_o_094.pdf","row_type":"noael_study","study_id":"sccs_o_094_noael_009"}
SCCS_vision_codex	NOAEL	=8	mg/kg bw/d	rabbit	dermal	90 day	NOAEL study	{"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.","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","page":17,"pdf":"sccs_o_094.pdf","row_type":"noael_study","study_id":"sccs_o_094_noael_010"}
SCCS_vision_codex	NOAEL	=16	mg/kg bw/d	rabbit	dermal	90 day	NOAEL study	{"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.","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","page":17,"pdf":"sccs_o_094.pdf","row_type":"noael_study","study_id":"sccs_o_094_noael_011"}
SCCS_vision_codex	NOAEL	=14	-	rat	-	-	NOAEL study	{"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","page":58,"pdf":"sccs_o_094.pdf","row_type":"noael_study","study_id":"sccs_o_094_noael_014"}
SCCS_vision_codex	NOAEL	=4	mg/kg bw/d	-	oral	90 days	NOAEL study	{"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_vision_codex	NOAEL	=0.04	mg/kg bw/d	rat	oral	subchronic	repeated dose toxicity	{"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","page":59,"pdf":"sccs_o_094.pdf","row_type":"noael_study","study_id":"sccs_o_094_noael_022"}
SCCS_vision_codex	NOAEL	=1	%	rat	oral	-	NOAEL study	{"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.","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","page":61,"pdf":"sccs_o_094.pdf","row_type":"noael_study","study_id":"sccs_o_094_noael_027"}
SCCS_vision_codex	NOAEL	=6.45	mg/kg bw	rat	oral	-	NOAEL study	{"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","page":61,"pdf":"sccs_o_094.pdf","row_type":"noael_study","study_id":"sccs_o_094_noael_029"}
SCCS_vision_codex	NOAEL	=8	mg/kg bw/day	rat	-	-	NOAEL study	{"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","page":66,"pdf":"sccs_o_094.pdf","row_type":"noael_study","study_id":"sccs_o_094_noael_047"}
SCCS_vision_codex	NOAEL	=61	-	-	oral	-	NOAEL study	{"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","page":61,"pdf":"sccs_o_094.pdf","row_type":"noael_study","study_id":"sccs_o_094_noael_048"}
SCCS_vision_codex	NOAEL	=8	-	-	oral	-	NOAEL study	{"effect":"Unlabeled table on page 61: Gavage NOAEL of 8 \| 22152 \| 1415 \| 15.6 \| 966 \| 22.2","page":61,"pdf":"sccs_o_094.pdf","row_type":"noael_study","study_id":"sccs_o_094_noael_057"}
SCCS_vision_codex	NOAEL	=16	-	-	oral	-	NOAEL study	{"effect":"Unlabeled table on page 61: Gavage NOAEL of 16 \| 44304 \| 1415 \| 31.3 \| 966 \| 45.9","page":61,"pdf":"sccs_o_094.pdf","row_type":"noael_study","study_id":"sccs_o_094_noael_058"}
SCCS_vision_codex	NOAEL	=50	-	-	oral	-	NOAEL study	{"effect":"Unlabeled table on page 61: Dietary NOEL of 50 \| 138450 \| 1415 \| 97.8 \| 966 \| 143.3","page":61,"pdf":"sccs_o_094.pdf","row_type":"noael_study","study_id":"sccs_o_094_noael_059"}
SCCS_vision_codex	NOAEL	=4	mg/kg bw	rat	-	-	carcinogenicity	{"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","page":5,"pdf":"sccs_o_094.pdf","row_type":"noael_study","study_id":"sccs_o_094_noael_001"}
SCCS_vision_codex	NOAEL	<5	mg/kg bw/day	rat	oral	Sub-chronic	repeated dose toxicity	{"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...","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","page":16,"pdf":"sccs_o_094.pdf","row_type":"noael_study","study_id":"sccs_o_094_noael_002"}
SCCS_vision_codex	NOAEL	=16	mg/kg bw	-	-	-	NOAEL study	{"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.","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","page":16,"pdf":"sccs_o_094.pdf","row_type":"noael_study","study_id":"sccs_o_094_noael_003"}
SCCS_vision_codex	NOAEL	=4	mg/kg bw/day	-	-	-	NOAEL study	{"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.","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","page":16,"pdf":"sccs_o_094.pdf","row_type":"noael_study","study_id":"sccs_o_094_noael_004"}
SCCS_vision_codex	NOAEL	=8	mg/kg bw	rat	oral	3 days	NOAEL study	{"citation":"(Ref. 120)","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","page":17,"pdf":"sccs_o_094.pdf","row_type":"noael_study","study_id":"sccs_o_094_noael_008"}
SCCS_vision_codex	NOAEL	=50	mg/kg bw	rat	oral	13-week	NOAEL study	{"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).","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","page":17,"pdf":"sccs_o_094.pdf","row_type":"noael_study","study_id":"sccs_o_094_noael_009"}
SCCS_vision_codex	NOAEL	=8	mg/kg bw/d	rabbit	dermal	90 day	NOAEL study	{"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.","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","page":17,"pdf":"sccs_o_094.pdf","row_type":"noael_study","study_id":"sccs_o_094_noael_010"}
SCCS_vision_codex	NOAEL	=16	mg/kg bw/d	rabbit	dermal	90 day	NOAEL study	{"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.","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","page":17,"pdf":"sccs_o_094.pdf","row_type":"noael_study","study_id":"sccs_o_094_noael_011"}
SCCS_vision_codex	NOAEL	=14	-	rat	-	-	NOAEL study	{"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","page":58,"pdf":"sccs_o_094.pdf","row_type":"noael_study","study_id":"sccs_o_094_noael_014"}
SCCS_vision_codex	NOAEL	=4	mg/kg bw/d	-	oral	90 days	NOAEL study	{"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_vision_codex	NOAEL	=0.04	mg/kg bw/d	rat	oral	subchronic	repeated dose toxicity	{"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","page":59,"pdf":"sccs_o_094.pdf","row_type":"noael_study","study_id":"sccs_o_094_noael_022"}
SCCS_vision_codex	NOAEL	=1	%	rat	oral	-	NOAEL study	{"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.","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","page":61,"pdf":"sccs_o_094.pdf","row_type":"noael_study","study_id":"sccs_o_094_noael_027"}
SCCS_vision_codex	NOAEL	=6.45	mg/kg bw	rat	oral	-	NOAEL study	{"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","page":61,"pdf":"sccs_o_094.pdf","row_type":"noael_study","study_id":"sccs_o_094_noael_029"}
SCCS_vision_codex	NOAEL	=8	mg/kg bw/day	rat	-	-	NOAEL study	{"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","page":66,"pdf":"sccs_o_094.pdf","row_type":"noael_study","study_id":"sccs_o_094_noael_047"}
SCCS_vision_codex	NOAEL	=61	-	-	oral	-	NOAEL study	{"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","page":61,"pdf":"sccs_o_094.pdf","row_type":"noael_study","study_id":"sccs_o_094_noael_048"}
SCCS_vision_codex	NOAEL	=8	-	-	oral	-	NOAEL study	{"effect":"Unlabeled table on page 61: Gavage NOAEL of 8 \| 22152 \| 1415 \| 15.6 \| 966 \| 22.2","page":61,"pdf":"sccs_o_094.pdf","row_type":"noael_study","study_id":"sccs_o_094_noael_057"}
SCCS_vision_codex	NOAEL	=16	-	-	oral	-	NOAEL study	{"effect":"Unlabeled table on page 61: Gavage NOAEL of 16 \| 44304 \| 1415 \| 31.3 \| 966 \| 45.9","page":61,"pdf":"sccs_o_094.pdf","row_type":"noael_study","study_id":"sccs_o_094_noael_058"}
SCCS_vision_codex	NOAEL	=50	-	-	oral	-	NOAEL study	{"effect":"Unlabeled table on page 61: Dietary NOEL of 50 \| 138450 \| 1415 \| 97.8 \| 966 \| 143.3","page":61,"pdf":"sccs_o_094.pdf","row_type":"noael_study","study_id":"sccs_o_094_noael_059"}
SCCS_vision_codex	NOAEL	<5	mg/kg bw/day	-	-	-	NOAEL study	{"citation":"Ref.: 120","dose":"blood chemistry changes resulted in both sexes at dose level of 5 mg/kg/day or greater (increased lactate dehydrogenase and creatine phosphokinase levels). - 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 t...","effect":"blood chemistry changes resulted in both sexes at dose level of 5 mg/kg/day or greater (increased lactate dehydrogenase and creatine phosphokinase levels). - 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 NOAEL was < 5 mg/kg bw/day. Ref.: 120","page":13,"pdf":"sccp_o_069.pdf","row_type":"noael_study","study_id":"sccp_o_069_noael_001"}
SCCS_vision_codex	NOAEL	=16	mg/kg bw	rat	oral	12-week	NOAEL study	{"citation":"Ref.: 121 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","dose":"-related liver weights were significantly increased for males given 8 mg/kg/day and 16 mg/kg/day.","effect":"-related liver weights were significantly increased for males given 8 mg/kg/day and 16 mg/kg/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 NOAEL of PPD was established at 4 mg/kg/day. Ref.: 121 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/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","page":14,"pdf":"sccp_o_069.pdf","row_type":"noael_study","study_id":"sccp_o_069_noael_002"}
SCCS_vision_codex	NOAEL	=50	mg/kg bw	rat	oral	-	NOAEL study	{"citation":"Ref.: 53","dose":"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/day respectively).","effect":"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/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","page":14,"pdf":"sccp_o_069.pdf","row_type":"noael_study","study_id":"sccp_o_069_noael_003"}
SCCS_vision_codex	NOAEL	=8	mg/kg	rabbit	dermal	90 day	NOAEL study	{"citation":"Ref.: 46 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.","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 for both sexes, the NOAEL was 16 mg/kg bw. Ref.: 46 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 and other hair-dye constituents were mixed with an equal volume of 6% hydrogen peroxide. A dose of 1 ml/kg of this mixture was applied for 1 hour without occlusion to three application sites on six animals of each sex. The application sites were abraded pri","page":15,"pdf":"sccp_o_069.pdf","row_type":"noael_study","study_id":"sccp_o_069_noael_004"}
SCCS_vision_codex	NOAEL	=5	mg/kg bw	human	-	developmental	developmental toxicity	{"citation":"Ref.: 8, subm","dose":"SCCP/0989/06 Opinion on p-phenylenediamine ____________________________________________________________________________________________ 46 The NOAEL of maternal toxicity is 5 mg/kg bw whereas the NOAEL of developmental toxicity is 10 mg/kg bw.","effect":"SCCP/0989/06 Opinion on p-phenylenediamine ____________________________________________________________________________________________ 46 The NOAEL of maternal toxicity is 5 mg/kg bw whereas the NOAEL of developmental toxicity is 10 mg/kg bw. Ref.: 8, subm. 12/2005 3.3.9. Toxicokinetics Human hepatic metabolism in vitro Guideline: / Cells: human hepatocytes, 4 male donors (cryo-preserved) Test substance: p-phenylenediamine dihydrochloride Sigma-Aldrich P6001 Radiolabeled substance: [14C(u)]-1,4-phenylenediamine dihydrochloride (14C PPD) Specific activity: 33.2 mCi/mmol Batch: Lot No. 10194-57-A Purity: > 98% Test system A hepatocytes (10 µM, 50 µM and 100","page":46,"pdf":"sccp_o_069.pdf","row_type":"noael_study","study_id":"sccp_o_069_noael_006"}
SCCS_vision_codex	NOAEL	=0.052	mg/kg bw	rat	oral	subchronic	repeated dose toxicity	{"dose":"Thus the usage volume of 100 ml contains at maximum 2.0% Highest penetration PA (µg/cm2) = 4.47 µg/cm2 Typical body weight of human = 60 kg Exposed area (scalp) = 700 cm2 Systemic exposure PA x 700 cm2 = 3.129 mg Systemic exposure dose (SED) PA x 700/ 60 x 1000 = 0.052 mg/kg bw No observed adverse effect level (mg/kg) NOAEL = 4 mg/kg bw (rat, or...","effect":"(including calculation of the MoS) Taken from SCCNFP/0129/99, adopted in 2002 CALCULATION OF THE MARGIN OF SAFETY (p-PHENYLENEDIAMINE) (Oxidative) The maximum concentration of 4.0% of p-Phenylenediamine is mixed before use with H2O2. Thus the usage volume of 100 ml contains at maximum 2.0% Highest penetration PA (µg/cm2) = 4.47 µg/cm2 Typical body weight of human = 60 kg Exposed area (scalp) = 700 cm2 Systemic exposure PA x 700 cm2 = 3.129 mg Systemic exposure dose (SED) PA x 700/ 60 x 1000 = 0.052 mg/kg bw No observed adverse effect level (mg/kg) NOAEL = 4 mg/kg bw (rat, oral, subchronic toxicity) Margin of Safety NOAEL / SED = 77","page":52,"pdf":"sccp_o_069.pdf","row_type":"noael_study","study_id":"sccp_o_069_noael_007"}
SCCS_vision_codex	NOAEL	=4	mg/kg bw	rat	oral	subchronic	repeated dose toxicity	{"dose":"Thus the usage volume of 100 ml contains at maximum 2.0% Highest penetration PA (µg/cm2) = 4.47 µg/cm2 Typical body weight of human = 60 kg Exposed area (scalp) = 700 cm2 Systemic exposure PA x 700 cm2 = 3.129 mg Systemic exposure dose (SED) PA x 700/ 60 x 1000 = 0.052 mg/kg bw No observed adverse effect level (mg/kg) NOAEL = 4 mg/kg bw (rat, or...","effect":"n from SCCNFP/0129/99, adopted in 2002 CALCULATION OF THE MARGIN OF SAFETY (p-PHENYLENEDIAMINE) (Oxidative) The maximum concentration of 4.0% of p-Phenylenediamine is mixed before use with H2O2. Thus the usage volume of 100 ml contains at maximum 2.0% Highest penetration PA (µg/cm2) = 4.47 µg/cm2 Typical body weight of human = 60 kg Exposed area (scalp) = 700 cm2 Systemic exposure PA x 700 cm2 = 3.129 mg Systemic exposure dose (SED) PA x 700/ 60 x 1000 = 0.052 mg/kg bw No observed adverse effect level (mg/kg) NOAEL = 4 mg/kg bw (rat, oral, subchronic toxicity) Margin of Safety NOAEL / SED = 77","page":52,"pdf":"sccp_o_069.pdf","row_type":"noael_study","study_id":"sccp_o_069_noael_008"}
SCCS_vision_codex	NOAEL	=4	mg/kg	rat	oral	90-day	NOAEL study	{"dose":"SCCP/0989/06 Opinion on p-phenylenediamine ____________________________________________________________________________________________ 53 Safety evaluation based on toxicokinetics (taken from dossier) 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/...","effect":"SCCP/0989/06 Opinion on p-phenylenediamine ____________________________________________________________________________________________ 53 Safety evaluation based on toxicokinetics (taken from dossier) 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) 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 i","page":53,"pdf":"sccp_o_069.pdf","row_type":"noael_study","study_id":"sccp_o_069_noael_010"}
SCCS_vision_codex	NOAEL	=2	%	rat	-	-	NOAEL study	{"citation":"(Reference 14)","dose":"Taking into account that the human study was performed under maximal exposure conditions, such as maximal PPD concentration (2.0%), short hair length (2 cm) of the treated subjects and","effect":"ifferences for toxicokinetics and toxicodynamics (Reference 14). Therefore, the AUC-based margin of safety for PPD is sufficiently high to conclude that the human systemic exposure from hair dyeing with a dark-shade, PPD-containing oxidative hair dye poses no risk to human health. This view is further supported by the margin of safety on the basis of human and rat Cmax values (45-fold), which gives additional assurance that human systemic exposure from PPD-containing hair dyes is far lower than that in rats at the NOAEL. Taking into account that the human study was performed under maximal exposure conditions, such as maximal PPD concentration (2.0%), short hair length (2 cm) of the treated subjects and","page":53,"pdf":"sccp_o_069.pdf","row_type":"noael_study","study_id":"sccp_o_069_noael_012"}
SCCS_vision_codex	NOAEL	=4	mg/kg bw	rat	-	-	carcinogenicity	{"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","page":5,"pdf":"sccs_o_094.pdf","row_type":"noael_study","study_id":"sccs_o_094_noael_001"}
SCCS_vision_codex	NOAEL	<5	mg/kg bw/day	rat	oral	Sub-chronic	repeated dose toxicity	{"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...","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","page":16,"pdf":"sccs_o_094.pdf","row_type":"noael_study","study_id":"sccs_o_094_noael_002"}
SCCS_vision_codex	NOAEL	=16	mg/kg bw	-	-	-	NOAEL study	{"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.","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","page":16,"pdf":"sccs_o_094.pdf","row_type":"noael_study","study_id":"sccs_o_094_noael_003"}
SCCS_vision_codex	NOAEL	=4	mg/kg bw/day	-	-	-	NOAEL study	{"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.","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","page":16,"pdf":"sccs_o_094.pdf","row_type":"noael_study","study_id":"sccs_o_094_noael_004"}
SCCS_vision_codex	NOAEL	=8	mg/kg bw	rat	oral	3 days	NOAEL study	{"citation":"(Ref. 120)","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","page":17,"pdf":"sccs_o_094.pdf","row_type":"noael_study","study_id":"sccs_o_094_noael_008"}
SCCS_vision_codex	NOAEL	=50	mg/kg bw	rat	oral	13-week	NOAEL study	{"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).","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","page":17,"pdf":"sccs_o_094.pdf","row_type":"noael_study","study_id":"sccs_o_094_noael_009"}
SCCS_vision_codex	NOAEL	=8	mg/kg bw/d	rabbit	dermal	90 day	NOAEL study	{"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.","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","page":17,"pdf":"sccs_o_094.pdf","row_type":"noael_study","study_id":"sccs_o_094_noael_010"}
SCCS_vision_codex	NOAEL	=16	mg/kg bw/d	rabbit	dermal	90 day	NOAEL study	{"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.","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","page":17,"pdf":"sccs_o_094.pdf","row_type":"noael_study","study_id":"sccs_o_094_noael_011"}
SCCS_vision_codex	NOAEL	=14	-	rat	-	-	NOAEL study	{"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","page":58,"pdf":"sccs_o_094.pdf","row_type":"noael_study","study_id":"sccs_o_094_noael_014"}
SCCS_vision_codex	NOAEL	=4	mg/kg bw/d	-	oral	90 days	NOAEL study	{"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_vision_codex	NOAEL	=0.04	mg/kg bw/d	rat	oral	subchronic	repeated dose toxicity	{"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","page":59,"pdf":"sccs_o_094.pdf","row_type":"noael_study","study_id":"sccs_o_094_noael_022"}
SCCS_vision_codex	NOAEL	=1	%	rat	oral	-	NOAEL study	{"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.","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","page":61,"pdf":"sccs_o_094.pdf","row_type":"noael_study","study_id":"sccs_o_094_noael_027"}
SCCS_vision_codex	NOAEL	=6.45	mg/kg bw	rat	oral	-	NOAEL study	{"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","page":61,"pdf":"sccs_o_094.pdf","row_type":"noael_study","study_id":"sccs_o_094_noael_029"}
SCCS_vision_codex	NOAEL	=8	mg/kg bw/day	rat	-	-	NOAEL study	{"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","page":66,"pdf":"sccs_o_094.pdf","row_type":"noael_study","study_id":"sccs_o_094_noael_047"}
SCCS_vision_codex	NOAEL	=61	-	-	oral	-	NOAEL study	{"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","page":61,"pdf":"sccs_o_094.pdf","row_type":"noael_study","study_id":"sccs_o_094_noael_048"}
SCCS_vision_codex	NOAEL	=8	-	-	oral	-	NOAEL study	{"effect":"Unlabeled table on page 61: Gavage NOAEL of 8 \| 22152 \| 1415 \| 15.6 \| 966 \| 22.2","page":61,"pdf":"sccs_o_094.pdf","row_type":"noael_study","study_id":"sccs_o_094_noael_057"}
SCCS_vision_codex	NOAEL	=16	-	-	oral	-	NOAEL study	{"effect":"Unlabeled table on page 61: Gavage NOAEL of 16 \| 44304 \| 1415 \| 31.3 \| 966 \| 45.9","page":61,"pdf":"sccs_o_094.pdf","row_type":"noael_study","study_id":"sccs_o_094_noael_058"}
SCCS_vision_codex	NOAEL	=50	-	-	oral	-	NOAEL study	{"effect":"Unlabeled table on page 61: Dietary NOEL of 50 \| 138450 \| 1415 \| 97.8 \| 966 \| 143.3","page":61,"pdf":"sccs_o_094.pdf","row_type":"noael_study","study_id":"sccs_o_094_noael_059"}

ToxValDB_ECHA_IUCLID 36 endpoints

Source	Endpoint Type	Value	Unit	Species	Route	Duration	Study Type	Reference
ToxValDB_ECHA_IUCLID	LEL	=5000	mg/kg bw/day	Rabbit	dermal	acute; 24 hours	acute	QUALITY=4 (not assignable); STORED_SOURCE_RECORD=https://clowder.edap-cluster.com/files/67c6183ae4b096bca876266c; RECORD_SOURCE_LEVEL=Extraction document; SOURCE_URL=https://echa.europa.eu/; SUBSOURCE_URL=https://echa.europa.eu/registration-dossier/-/registered-dossier/22562/7/3/4?documentUUID=62c6f81b-e4db-4e99-8e98-f7a3329411b2; YEAR=2010; ORIGINAL_YEAR=2010; STUDY_GROUP=ECHA IUCLID:15792534:-:--; QC_CATEGORY=Programmatically extracted from structured data source; Source overall passed QC, but this record was not manually checked; QC_STATUS=not determined; SOURCE_HASH=ToxValhc_9d88c86b33fb505a6ce2cb6c6eac5154
ToxValDB_ECHA_IUCLID	LEL	=357	mg/kg bw/day	Dog	oral	-	acute	QUALITY=4 (not assignable); STORED_SOURCE_RECORD=https://clowder.edap-cluster.com/files/6605975fe4b063812d6fa6ed; RECORD_SOURCE_LEVEL=Extraction document; SOURCE_URL=https://echa.europa.eu/; SUBSOURCE_URL=https://echa.europa.eu/registration-dossier/-/registered-dossier/22562/7/3/2?documentUUID=62c6f81b-e4db-4e99-8e98-f7a3329411b2; YEAR=2010; ORIGINAL_YEAR=2010; STUDY_GROUP=ECHA IUCLID_dup_Acute Toxicity Oral_15800395_15801350:-:--; QC_CATEGORY=Programmatically extracted from structured data source; Source overall passed QC, but this record was not manually checked; QC_STATUS=not determined; SOURCE_HASH=ToxValhc_bbc4987e3c3d126be7566b54a8adfc31
ToxValDB_ECHA_IUCLID	LEL	>=1	mg/kg bw/day	Dog	oral	-	acute	QUALITY=4 (not assignable); STORED_SOURCE_RECORD=https://clowder.edap-cluster.com/files/6605975fe4b063812d6fa6ed; RECORD_SOURCE_LEVEL=Extraction document; SOURCE_URL=https://echa.europa.eu/; SUBSOURCE_URL=https://echa.europa.eu/registration-dossier/-/registered-dossier/22562/7/3/2?documentUUID=62c6f81b-e4db-4e99-8e98-f7a3329411b2; YEAR=2010; ORIGINAL_YEAR=2010; STUDY_GROUP=ECHA IUCLID_dup_Acute Toxicity Oral_15800395_15801350:-:--; QC_CATEGORY=Programmatically extracted from structured data source; Source overall passed QC, but this record was not manually checked; QC_STATUS=not determined; SOURCE_HASH=ToxValhc_8f59c7fa8fad5784b16af70f537722d2
ToxValDB_ECHA_IUCLID	LEL	=75	mg/kg bw/day	Rat	oral	-	acute	QUALITY=1 (reliable without restriction); STORED_SOURCE_RECORD=https://clowder.edap-cluster.com/files/6605975fe4b063812d6fa6ed; RECORD_SOURCE_LEVEL=Extraction document; SOURCE_URL=https://echa.europa.eu/; SUBSOURCE_URL=https://echa.europa.eu/registration-dossier/-/registered-dossier/22562/7/3/2?documentUUID=62c6f81b-e4db-4e99-8e98-f7a3329411b2; YEAR=2010; ORIGINAL_YEAR=2010; STUDY_GROUP=ECHA IUCLID:15804937:F:--; QC_CATEGORY=Programmatically extracted from structured data source; Source overall passed QC, but this record was not manually checked; QC_STATUS=not determined; SOURCE_HASH=ToxValhc_03dab6d91bb5ee835936ad2ec4989762
ToxValDB_ECHA_IUCLID	LEL	>=200	mg/kg bw/day	Rabbit	oral	-	acute	QUALITY=4 (not assignable); STORED_SOURCE_RECORD=https://clowder.edap-cluster.com/files/6605975fe4b063812d6fa6ed; RECORD_SOURCE_LEVEL=Extraction document; SOURCE_URL=https://echa.europa.eu/; SUBSOURCE_URL=https://echa.europa.eu/registration-dossier/-/registered-dossier/22562/7/3/2?documentUUID=62c6f81b-e4db-4e99-8e98-f7a3329411b2; YEAR=2010; ORIGINAL_YEAR=2010; STUDY_GROUP=ECHA IUCLID_dup_Acute Toxicity Oral_15807683_15814669_15814670:-:--; QC_CATEGORY=Programmatically extracted from structured data source; Source overall passed QC, but this record was not manually checked; QC_STATUS=not determined; SOURCE_HASH=ToxValhc_b24b3d80e41ec552181dc948ce92c4d6
ToxValDB_ECHA_IUCLID	LEL	>=20	mg/kg bw/day	Cat	oral	-	acute	QUALITY=4 (not assignable); STORED_SOURCE_RECORD=https://clowder.edap-cluster.com/files/6605975fe4b063812d6fa6ed; RECORD_SOURCE_LEVEL=Extraction document; SOURCE_URL=https://echa.europa.eu/; SUBSOURCE_URL=https://echa.europa.eu/registration-dossier/-/registered-dossier/22562/7/3/2?documentUUID=62c6f81b-e4db-4e99-8e98-f7a3329411b2; YEAR=2010; ORIGINAL_YEAR=2010; STUDY_GROUP=ECHA IUCLID:15808949:-:--; QC_CATEGORY=Programmatically extracted from structured data source; Source overall passed QC, but this record was not manually checked; QC_STATUS=not determined; SOURCE_HASH=ToxValhc_ee921decd061d2e8528acc5a68c67ade
ToxValDB_ECHA_IUCLID	LEL	<=270	mg/kg bw/day	Rabbit	oral	-	acute	QUALITY=4 (not assignable); STORED_SOURCE_RECORD=https://clowder.edap-cluster.com/files/6605975fe4b063812d6fa6ed; RECORD_SOURCE_LEVEL=Extraction document; SOURCE_URL=https://echa.europa.eu/; SUBSOURCE_URL=https://echa.europa.eu/registration-dossier/-/registered-dossier/22562/7/3/2?documentUUID=62c6f81b-e4db-4e99-8e98-f7a3329411b2; YEAR=2010; ORIGINAL_YEAR=2010; STUDY_GROUP=ECHA IUCLID_dup_Acute Toxicity Oral_15807683_15814669_15814670:-:--; QC_CATEGORY=Programmatically extracted from structured data source; Source overall passed QC, but this record was not manually checked; QC_STATUS=not determined; SOURCE_HASH=ToxValhc_d7b8add6be0ff0a2d9590bf576464053
ToxValDB_ECHA_IUCLID	LEL	=100	mg/kg bw/day	Dog	injection	-	acute	QUALITY=4 (not assignable); STORED_SOURCE_RECORD=https://clowder.edap-cluster.com/files/67c61bdfe4b096bca876fc38; RECORD_SOURCE_LEVEL=Extraction document; SOURCE_URL=https://echa.europa.eu/; SUBSOURCE_URL=https://echa.europa.eu/registration-dossier/-/registered-dossier/22562/7/3/5?documentUUID=62c6f81b-e4db-4e99-8e98-f7a3329411b2; YEAR=2010; ORIGINAL_YEAR=2010; STUDY_GROUP=ECHA IUCLID:15815063:-:--; QC_CATEGORY=Programmatically extracted from structured data source; Source overall passed QC, but this record was not manually checked; QC_STATUS=not determined; SOURCE_HASH=ToxValhc_80251e807643e9c0cb7365b38daa0fc4
ToxValDB_ECHA_IUCLID	LEL	=215	mg/kg bw/day	Cat	injection	-	acute	QUALITY=4 (not assignable); STORED_SOURCE_RECORD=https://clowder.edap-cluster.com/files/67c61bdfe4b096bca876fc4c; RECORD_SOURCE_LEVEL=Extraction document; SOURCE_URL=https://echa.europa.eu/; SUBSOURCE_URL=https://echa.europa.eu/registration-dossier/-/registered-dossier/22562/7/3/5?documentUUID=62c6f81b-e4db-4e99-8e98-f7a3329411b2; YEAR=2010; ORIGINAL_YEAR=2010; STUDY_GROUP=ECHA IUCLID_dup_Acute Toxicity Other Routes_15815067_15815310:-:--; QC_CATEGORY=Programmatically extracted from structured data source; Source overall passed QC, but this record was not manually checked; QC_STATUS=not determined; SOURCE_HASH=ToxValhc_604d3c76a7ef431953983081fbdd4f87
ToxValDB_ECHA_IUCLID	LEL	=50	mg/kg bw/day	Rat	injection	-	acute	QUALITY=4 (not assignable); STORED_SOURCE_RECORD=https://clowder.edap-cluster.com/files/67c61c13e4b096bca8770883; RECORD_SOURCE_LEVEL=Extraction document; SOURCE_URL=https://echa.europa.eu/; SUBSOURCE_URL=https://echa.europa.eu/registration-dossier/-/registered-dossier/22562/7/3/5?documentUUID=62c6f81b-e4db-4e99-8e98-f7a3329411b2; YEAR=2010; ORIGINAL_YEAR=2010; STUDY_GROUP=ECHA IUCLID_dup_Acute Toxicity Other Routes_15815191_15815192:-:--; QC_CATEGORY=Programmatically extracted from structured data source; Source overall passed QC, but this record was not manually checked; QC_STATUS=not determined; SOURCE_HASH=ToxValhc_8cdfd7cad7f6d7c41d0757ba5828467d
ToxValDB_ECHA_IUCLID	LEL	=30	mg/kg bw/day	Dog	injection	-	acute	QUALITY=4 (not assignable); STORED_SOURCE_RECORD=https://clowder.edap-cluster.com/files/67c61c24e4b096bca8770d11; RECORD_SOURCE_LEVEL=Extraction document; SOURCE_URL=https://echa.europa.eu/; SUBSOURCE_URL=https://echa.europa.eu/registration-dossier/-/registered-dossier/22562/7/3/5?documentUUID=62c6f81b-e4db-4e99-8e98-f7a3329411b2; YEAR=2010; ORIGINAL_YEAR=2010; STUDY_GROUP=ECHA IUCLID_dup_Acute Toxicity Other Routes_15815249_15815256_15815283_15815637:-:--; QC_CATEGORY=Programmatically extracted from structured data source; Source overall passed QC, but this record was not manually checked; QC_STATUS=not determined; SOURCE_HASH=ToxValhc_909402e62e53e469401d480bc07515ee
ToxValDB_ECHA_IUCLID	LEL	=600	mg/kg bw/day	Rat	injection	-	acute	QUALITY=4 (not assignable); STORED_SOURCE_RECORD=https://clowder.edap-cluster.com/files/67c61c35e4b096bca877109a; RECORD_SOURCE_LEVEL=Extraction document; SOURCE_URL=https://echa.europa.eu/; SUBSOURCE_URL=https://echa.europa.eu/registration-dossier/-/registered-dossier/22562/7/3/5?documentUUID=62c6f81b-e4db-4e99-8e98-f7a3329411b2; YEAR=2010; ORIGINAL_YEAR=2010; STUDY_GROUP=ECHA IUCLID_dup_Acute Toxicity Other Routes_15815276_15815520_15816015_15816016:-:--; QC_CATEGORY=Programmatically extracted from structured data source; Source overall passed QC, but this record was not manually checked; QC_STATUS=not determined; SOURCE_HASH=ToxValhc_efd548b6f44931d525a5ccb8b0123bcd
ToxValDB_ECHA_IUCLID	LEL	>=52	mg/kg bw/day	Rabbit	injection	-	acute	QUALITY=4 (not assignable); STORED_SOURCE_RECORD=https://clowder.edap-cluster.com/files/67c61c66e4b096bca8771d9c; RECORD_SOURCE_LEVEL=Extraction document; SOURCE_URL=https://echa.europa.eu/; SUBSOURCE_URL=https://echa.europa.eu/registration-dossier/-/registered-dossier/22562/7/3/5?documentUUID=62c6f81b-e4db-4e99-8e98-f7a3329411b2; YEAR=2010; ORIGINAL_YEAR=2010; STUDY_GROUP=ECHA IUCLID_dup_Acute Toxicity Other Routes_15815423_15815500_15815630_15815823_15815979_15815980:-:--; QC_CATEGORY=Programmatically extracted from structured data source; Source overall passed QC, but this record was not manually checked; QC_STATUS=not determined; SOURCE_HASH=ToxValhc_afbb032d0628bd6db497c736833ca251
ToxValDB_ECHA_IUCLID	LEL	=400	mg/kg bw/day	Rabbit	injection	-	acute	QUALITY=4 (not assignable); STORED_SOURCE_RECORD=https://clowder.edap-cluster.com/files/67c61ccce4b096bca8773706; RECORD_SOURCE_LEVEL=Extraction document; SOURCE_URL=https://echa.europa.eu/; SUBSOURCE_URL=https://echa.europa.eu/registration-dossier/-/registered-dossier/22562/7/3/5?documentUUID=62c6f81b-e4db-4e99-8e98-f7a3329411b2; YEAR=2010; ORIGINAL_YEAR=2010; STUDY_GROUP=ECHA IUCLID_dup_Acute Toxicity Other Routes_15815423_15815500_15815630_15815823_15815979_15815980:-:--; QC_CATEGORY=Programmatically extracted from structured data source; Source overall passed QC, but this record was not manually checked; QC_STATUS=not determined; SOURCE_HASH=ToxValhc_0147e3913e3e6b235c73c524a9d16166
ToxValDB_ECHA_IUCLID	LEL	=70	mg/kg bw/day	Dog	injection	-	acute	QUALITY=4 (not assignable); STORED_SOURCE_RECORD=https://clowder.edap-cluster.com/files/67c61ccce4b096bca877377a; RECORD_SOURCE_LEVEL=Extraction document; SOURCE_URL=https://echa.europa.eu/; SUBSOURCE_URL=https://echa.europa.eu/registration-dossier/-/registered-dossier/22562/7/3/5?documentUUID=62c6f81b-e4db-4e99-8e98-f7a3329411b2; YEAR=2010; ORIGINAL_YEAR=2010; STUDY_GROUP=ECHA IUCLID_dup_Acute Toxicity Other Routes_15815249_15815256_15815283_15815637:-:--; QC_CATEGORY=Programmatically extracted from structured data source; Source overall passed QC, but this record was not manually checked; QC_STATUS=not determined; SOURCE_HASH=ToxValhc_33b79ef49dc6cd5d1bb343de6cae1427
ToxValDB_ECHA_IUCLID	LEL	=140	mg/kg bw/day	Mouse	injection	-	acute	QUALITY=4 (not assignable); STORED_SOURCE_RECORD=https://clowder.edap-cluster.com/files/67c61d0de4b096bca877465f; RECORD_SOURCE_LEVEL=Extraction document; SOURCE_URL=https://echa.europa.eu/; SUBSOURCE_URL=https://echa.europa.eu/registration-dossier/-/registered-dossier/22562/7/3/5?documentUUID=62c6f81b-e4db-4e99-8e98-f7a3329411b2; YEAR=2010; ORIGINAL_YEAR=2010; STUDY_GROUP=ECHA IUCLID:15815773:-:--; QC_CATEGORY=Programmatically extracted from structured data source; Source overall passed QC, but this record was not manually checked; QC_STATUS=not determined; SOURCE_HASH=ToxValhc_6cfad608d1829482649330ba39fc4395
ToxValDB_ECHA_IUCLID	LEL	>=150	mg/kg bw/day	Rabbit	injection	-	acute	QUALITY=4 (not assignable); STORED_SOURCE_RECORD=https://clowder.edap-cluster.com/files/67c61c02e4b096bca8770494; RECORD_SOURCE_LEVEL=Extraction document; SOURCE_URL=https://echa.europa.eu/; SUBSOURCE_URL=https://echa.europa.eu/registration-dossier/-/registered-dossier/22562/7/3/5?documentUUID=62c6f81b-e4db-4e99-8e98-f7a3329411b2; YEAR=2010; ORIGINAL_YEAR=2010; STUDY_GROUP=ECHA IUCLID_dup_Acute Toxicity Other Routes_15815282_15815867_15815868:-:--; QC_CATEGORY=Programmatically extracted from structured data source; Source overall passed QC, but this record was not manually checked; QC_STATUS=not determined; SOURCE_HASH=ToxValhc_a53f89983990de8054ed3c067bb240f6
ToxValDB_ECHA_IUCLID	LEL	>=10	mg/kg bw/day	Rat	oral	-	acute	QUALITY=4 (not assignable); STORED_SOURCE_RECORD=https://clowder.edap-cluster.com/files/67c61cbce4b096bca877335f; RECORD_SOURCE_LEVEL=Extraction document; SOURCE_URL=https://echa.europa.eu/; SUBSOURCE_URL=https://echa.europa.eu/registration-dossier/-/registered-dossier/22562/7/3/5?documentUUID=62c6f81b-e4db-4e99-8e98-f7a3329411b2; YEAR=2010; ORIGINAL_YEAR=2010; STUDY_GROUP=ECHA IUCLID_dup_Acute Toxicity Other Routes_15815961_15815962:-:--; QC_CATEGORY=Programmatically extracted from structured data source; Source overall passed QC, but this record was not manually checked; QC_STATUS=not determined; SOURCE_HASH=ToxValhc_4251e5bef86f2fcddf5f5e533da4c95d
ToxValDB_ECHA_IUCLID	LEL	>=300	mg/kg bw/day	Rabbit	injection	-	acute	QUALITY=4 (not assignable); STORED_SOURCE_RECORD=https://clowder.edap-cluster.com/files/67c61cdce4b096bca87739d3; RECORD_SOURCE_LEVEL=Extraction document; SOURCE_URL=https://echa.europa.eu/; SUBSOURCE_URL=https://echa.europa.eu/registration-dossier/-/registered-dossier/22562/7/3/5?documentUUID=62c6f81b-e4db-4e99-8e98-f7a3329411b2; YEAR=2010; ORIGINAL_YEAR=2010; STUDY_GROUP=ECHA IUCLID_dup_Acute Toxicity Other Routes_15815423_15815500_15815630_15815823_15815979_15815980:-:--; QC_CATEGORY=Programmatically extracted from structured data source; Source overall passed QC, but this record was not manually checked; QC_STATUS=not determined; SOURCE_HASH=ToxValhc_f21755a95c907daf38c15c86bae48f7a
ToxValDB_ECHA_IUCLID	LEL	<=500	mg/kg bw/day	Rabbit	injection	-	acute	QUALITY=4 (not assignable); STORED_SOURCE_RECORD=https://clowder.edap-cluster.com/files/67c61cdce4b096bca87739d3; RECORD_SOURCE_LEVEL=Extraction document; SOURCE_URL=https://echa.europa.eu/; SUBSOURCE_URL=https://echa.europa.eu/registration-dossier/-/registered-dossier/22562/7/3/5?documentUUID=62c6f81b-e4db-4e99-8e98-f7a3329411b2; YEAR=2010; ORIGINAL_YEAR=2010; STUDY_GROUP=ECHA IUCLID_dup_Acute Toxicity Other Routes_15815423_15815500_15815630_15815823_15815979_15815980:-:--; QC_CATEGORY=Programmatically extracted from structured data source; Source overall passed QC, but this record was not manually checked; QC_STATUS=not determined; SOURCE_HASH=ToxValhc_b89db330a540ed705bb75eb569ea5051
ToxValDB_ECHA_IUCLID	LEL	=12.5	mg/kg bw/day	Rat	injection	-	chronic	QUALITY=4 (not assignable); STORED_SOURCE_RECORD=https://clowder.edap-cluster.com/files/66a7c7fbe4b0a7c65d215ea1; RECORD_SOURCE_LEVEL=Extraction document; SOURCE_URL=https://echa.europa.eu/; SUBSOURCE_URL=https://echa.europa.eu/registration-dossier/-/registered-dossier/22562/7/8?documentUUID=62c6f81b-e4db-4e99-8e98-f7a3329411b2; YEAR=2010; ORIGINAL_YEAR=2010; STUDY_GROUP=ECHA IUCLID_dup_Carcinogenicity_15818249_15818250:-:--; QC_CATEGORY=Programmatically extracted from structured data source; Source overall passed QC, but this record was not manually checked; QC_STATUS=not determined; SOURCE_HASH=ToxValhc_a193c47b5037cae32c6dfc8320b9fdcc
ToxValDB_ECHA_IUCLID	LEL	=1050	mg/kg bw/day	Rat	oral	chronic; 30 weeks	chronic	QUALITY=4 (not assignable); STORED_SOURCE_RECORD=https://clowder.edap-cluster.com/files/67c62039e4b096bca8780807; RECORD_SOURCE_LEVEL=Extraction document; SOURCE_URL=https://echa.europa.eu/; SUBSOURCE_URL=https://echa.europa.eu/registration-dossier/-/registered-dossier/22562/7/6/5?documentUUID=62c6f81b-e4db-4e99-8e98-f7a3329411b2; YEAR=2010; ORIGINAL_YEAR=2010; STUDY_GROUP=ECHA IUCLID:15852179:-:--; QC_CATEGORY=Programmatically extracted from structured data source; Source overall passed QC, but this record was not manually checked; QC_STATUS=not determined; SOURCE_HASH=ToxValhc_73f0e96cc8a3d9055af730a7fd88602d
ToxValDB_ECHA_IUCLID	LEL	=28000	mg/kg bw/day	Rat	oral	chronic; 80 weeks	chronic	QUALITY=4 (not assignable); STORED_SOURCE_RECORD=https://clowder.edap-cluster.com/files/67c6206ae4b096bca87813e1; RECORD_SOURCE_LEVEL=Extraction document; SOURCE_URL=https://echa.europa.eu/; SUBSOURCE_URL=https://echa.europa.eu/registration-dossier/-/registered-dossier/22562/7/6/5?documentUUID=62c6f81b-e4db-4e99-8e98-f7a3329411b2; YEAR=2010; ORIGINAL_YEAR=2010; STUDY_GROUP=ECHA IUCLID:15852809:-:--; QC_CATEGORY=Programmatically extracted from structured data source; Source overall passed QC, but this record was not manually checked; QC_STATUS=not determined; SOURCE_HASH=ToxValhc_7f6da65c1543506fd8e07d9e80a6a3c2
ToxValDB_ECHA_IUCLID	LEL	=105	mg/kg bw/day	Rabbit	oral	chronic; 30 weeks	chronic	QUALITY=4 (not assignable); STORED_SOURCE_RECORD=https://clowder.edap-cluster.com/files/67c620c0e4b096bca8782884; RECORD_SOURCE_LEVEL=Extraction document; SOURCE_URL=https://echa.europa.eu/; SUBSOURCE_URL=https://echa.europa.eu/registration-dossier/-/registered-dossier/22562/7/6/5?documentUUID=62c6f81b-e4db-4e99-8e98-f7a3329411b2; YEAR=2010; ORIGINAL_YEAR=2010; STUDY_GROUP=ECHA IUCLID:15853941:-:--; QC_CATEGORY=Programmatically extracted from structured data source; Source overall passed QC, but this record was not manually checked; QC_STATUS=not determined; SOURCE_HASH=ToxValhc_b9de624a0b115088e8c0b2935c71000f
ToxValDB_ECHA_IUCLID	LOAEL	=1	mg/kg bw/day	Rat	dermal	subchronic; 90 days	subchronic	QUALITY=2 (reliable with restrictions); STORED_SOURCE_RECORD=https://clowder.edap-cluster.com/files/67c61ef6e4b096bca877bccf; RECORD_SOURCE_LEVEL=Extraction document; SOURCE_URL=https://echa.europa.eu/; SUBSOURCE_URL=https://echa.europa.eu/registration-dossier/-/registered-dossier/22562/7/6/4?documentUUID=62c6f81b-e4db-4e99-8e98-f7a3329411b2; YEAR=2010; ORIGINAL_YEAR=2010; TOXICOLOGICAL_EFFECT=spleen; TOXICOLOGICAL_EFFECT_CATEGORY=other; STUDY_GROUP=ECHA IUCLID_dup_Repeated Dose Toxicity Dermal_15826703_15826781:M:--; QC_CATEGORY=Programmatically extracted from structured data source; Source overall passed QC, but this record was not manually checked; QC_STATUS=not determined; SOURCE_HASH=ToxValhc_c3fb5b3f62f5743588a080d9af9f9581
ToxValDB_ECHA_IUCLID	NOAEL	=10	mg/kg bw/day	Rat	oral	-	developmental	QUALITY=1 (reliable without restriction); STORED_SOURCE_RECORD=https://clowder.edap-cluster.com/files/669eabace4b0a7c65d1bb3d1; RECORD_SOURCE_LEVEL=Extraction document; SOURCE_URL=https://echa.europa.eu/; SUBSOURCE_URL=https://echa.europa.eu/registration-dossier/-/registered-dossier/22562/7/9/3?documentUUID=62c6f81b-e4db-4e99-8e98-f7a3329411b2; YEAR=2010; ORIGINAL_YEAR=2010; STUDY_GROUP=ECHA IUCLID:15821891:-:-fetal; QC_CATEGORY=Programmatically extracted from structured data source; Source overall passed QC, and this record was expert reviewed; QC_STATUS=pass; SOURCE_HASH=ToxValhc_ffbf0eaa81f05999e74a4c79314337c0
ToxValDB_ECHA_IUCLID	NOAEL	<20	ppm	Rat	oral	-	repeat dose other	QUALITY=1 (reliable without restriction); STORED_SOURCE_RECORD=https://clowder.edap-cluster.com/files/669eaa3ee4b0a7c65d1b4ec2; RECORD_SOURCE_LEVEL=Extraction document; SOURCE_URL=https://echa.europa.eu/; SUBSOURCE_URL=https://echa.europa.eu/registration-dossier/-/registered-dossier/22562/7/10/1?documentUUID=62c6f81b-e4db-4e99-8e98-f7a3329411b2; YEAR=2010; ORIGINAL_YEAR=2010; STUDY_GROUP=ECHA IUCLID:15825549:M/F:--; QC_CATEGORY=Programmatically extracted from structured data source; Source overall passed QC, but this record was not manually checked; QC_STATUS=not determined; SOURCE_HASH=ToxValhc_80b7467f3dac829a53a5cd282fbc781f
ToxValDB_ECHA_IUCLID	NOAEL	=16	mg/kg bw/day	Rat	oral	subchronic; 90 days	subchronic	QUALITY=1 (reliable without restriction); STORED_SOURCE_RECORD=https://clowder.edap-cluster.com/files/669eacc0e4b0a7c65d1c0a83; RECORD_SOURCE_LEVEL=Extraction document; SOURCE_URL=https://echa.europa.eu/; SUBSOURCE_URL=https://echa.europa.eu/registration-dossier/-/registered-dossier/22562/7/6/2?documentUUID=62c6f81b-e4db-4e99-8e98-f7a3329411b2; YEAR=2010; ORIGINAL_YEAR=2010; STUDY_GROUP=ECHA IUCLID:15835146:M/F:--; QC_CATEGORY=Programmatically extracted from structured data source; Source overall passed QC, and this record was expert reviewed; QC_STATUS=pass; SOURCE_HASH=ToxValhc_48bc68ddb3c74ecb7b602dd1842393d5
ToxValDB_ECHA_IUCLID	NOEL	=30	mg/kg bw/day	Rat	oral	-	developmental	QUALITY=4 (not assignable); STORED_SOURCE_RECORD=https://clowder.edap-cluster.com/files/669eabace4b0a7c65d1bb3cd; RECORD_SOURCE_LEVEL=Extraction document; SOURCE_URL=https://echa.europa.eu/; SUBSOURCE_URL=https://echa.europa.eu/registration-dossier/-/registered-dossier/22562/7/9/3?documentUUID=62c6f81b-e4db-4e99-8e98-f7a3329411b2; YEAR=2010; ORIGINAL_YEAR=2010; STUDY_GROUP=ECHA IUCLID_dup_Developmental Toxicity Teratogenicity_15820880_15821833:-:-fetal; QC_CATEGORY=Programmatically extracted from structured data source; Source overall passed QC, and this record was expert reviewed; QC_STATUS=pass; SOURCE_HASH=ToxValhc_8450a383d2ac83dfb77550774ceaea69
ToxValDB_ECHA_IUCLID	NOEL	=10	mg/kg bw/day	Rat	oral	-	reproduction developmental	QUALITY=2 (reliable with restrictions); STORED_SOURCE_RECORD=https://clowder.edap-cluster.com/files/669eabace4b0a7c65d1bb3cf; RECORD_SOURCE_LEVEL=Extraction document; SOURCE_URL=https://echa.europa.eu/; SUBSOURCE_URL=https://echa.europa.eu/registration-dossier/-/registered-dossier/22562/7/9/3?documentUUID=62c6f81b-e4db-4e99-8e98-f7a3329411b2; YEAR=2010; ORIGINAL_YEAR=2010; STUDY_GROUP=ECHA IUCLID:15823113:F:-maternal; QC_CATEGORY=Programmatically extracted from structured data source; Source overall passed QC, and this record was expert reviewed; QC_STATUS=pass; SOURCE_HASH=ToxValhc_2c61c596f687f60a38bf4a170a7d0411
ToxValDB_ECHA_IUCLID	NOEL	=5	mg/kg bw/day	Rat	oral	-	reproduction developmental	QUALITY=1 (reliable without restriction); STORED_SOURCE_RECORD=https://clowder.edap-cluster.com/files/669eabace4b0a7c65d1bb3d1; RECORD_SOURCE_LEVEL=Extraction document; SOURCE_URL=https://echa.europa.eu/; SUBSOURCE_URL=https://echa.europa.eu/registration-dossier/-/registered-dossier/22562/7/9/3?documentUUID=62c6f81b-e4db-4e99-8e98-f7a3329411b2; YEAR=2010; ORIGINAL_YEAR=2010; STUDY_GROUP=ECHA IUCLID:15823161:F:-maternal; QC_CATEGORY=Programmatically extracted from structured data source; Source overall passed QC, and this record was expert reviewed; QC_STATUS=pass; SOURCE_HASH=ToxValhc_4c60b607b759284976183d41c4678d69
ToxValDB_ECHA_IUCLID	NOEL	=80	mg/kg bw/day	Rat	oral	-	repeat dose other	QUALITY=1 (reliable without restriction); STORED_SOURCE_RECORD=https://clowder.edap-cluster.com/files/669eaa3ee4b0a7c65d1b4ec2; RECORD_SOURCE_LEVEL=Extraction document; SOURCE_URL=https://echa.europa.eu/; SUBSOURCE_URL=https://echa.europa.eu/registration-dossier/-/registered-dossier/22562/7/10/1?documentUUID=62c6f81b-e4db-4e99-8e98-f7a3329411b2; YEAR=2010; ORIGINAL_YEAR=2010; STUDY_GROUP=ECHA IUCLID_dup_Neurotoxicity_15825550_15825846_15825847:M/F:--; QC_CATEGORY=Programmatically extracted from structured data source; Source overall passed QC, and this record was expert reviewed; QC_STATUS=pass; SOURCE_HASH=ToxValhc_f7e71407d0dc90e0b31ba194bcc30652
ToxValDB_ECHA_IUCLID	NOEL	=16	mg/kg bw/day	Rat	oral	-	repeat dose other	GUIDELINE=EPA OTS 798.6050 (Neurotoxicity Screening Battery); QUALITY=1 (reliable without restriction); STORED_SOURCE_RECORD=https://clowder.edap-cluster.com/files/66a7c85ae4b0a7c65d2180ce; RECORD_SOURCE_LEVEL=Extraction document; SOURCE_URL=https://echa.europa.eu/; SUBSOURCE_URL=https://echa.europa.eu/registration-dossier/-/registered-dossier/22562/7/10/1?documentUUID=62c6f81b-e4db-4e99-8e98-f7a3329411b2; YEAR=2010; ORIGINAL_YEAR=2010; STUDY_GROUP=ECHA IUCLID_dup_Neurotoxicity_15825550_15825846_15825847:M/F:--; QC_CATEGORY=Programmatically extracted from structured data source; Source overall passed QC, but this record was not manually checked; QC_STATUS=not determined; SOURCE_HASH=ToxValhc_8445d310e2473200a69bf67a0da12608
ToxValDB_ECHA_IUCLID	NOEL	=8	mg/kg bw/day	Rat	oral	-	repeat dose other	GUIDELINE=EPA OTS 798.6050 (Neurotoxicity Screening Battery); QUALITY=1 (reliable without restriction); STORED_SOURCE_RECORD=https://clowder.edap-cluster.com/files/66a7c85ae4b0a7c65d2180ce; RECORD_SOURCE_LEVEL=Extraction document; SOURCE_URL=https://echa.europa.eu/; SUBSOURCE_URL=https://echa.europa.eu/registration-dossier/-/registered-dossier/22562/7/10/1?documentUUID=62c6f81b-e4db-4e99-8e98-f7a3329411b2; YEAR=2010; ORIGINAL_YEAR=2010; STUDY_GROUP=ECHA IUCLID_dup_Neurotoxicity_15825550_15825846_15825847:M/F:--; QC_CATEGORY=Programmatically extracted from structured data source; Source overall passed QC, but this record was not manually checked; QC_STATUS=not determined; SOURCE_HASH=ToxValhc_f890bcf50e6ce082cf1e268503941eda
ToxValDB_ECHA_IUCLID	NOEL	=65.376	mg/kg bw/day	Rat	oral	subchronic; 7 weeks	subchronic	QUALITY=2 (reliable with restrictions); STORED_SOURCE_RECORD=https://clowder.edap-cluster.com/files/669eacc0e4b0a7c65d1c0a85; RECORD_SOURCE_LEVEL=Extraction document; SOURCE_URL=https://echa.europa.eu/; SUBSOURCE_URL=https://echa.europa.eu/registration-dossier/-/registered-dossier/22562/7/6/2?documentUUID=62c6f81b-e4db-4e99-8e98-f7a3329411b2; YEAR=2010; ORIGINAL_YEAR=2010; STUDY_GROUP=ECHA IUCLID:15844240:F:--; QC_CATEGORY=Programmatically extracted from structured data source; Source overall passed QC, and this record was expert reviewed; QC_STATUS=pass; SOURCE_HASH=ToxValhc_2e31cedf8f129f9420464ebf745e10e3
ToxValDB_ECHA_IUCLID	NOEL	=96	mg/kg bw/day	Rat	oral	subchronic; 7 weeks	subchronic	QUALITY=2 (reliable with restrictions); STORED_SOURCE_RECORD=https://clowder.edap-cluster.com/files/669eacc0e4b0a7c65d1c0a85; RECORD_SOURCE_LEVEL=Extraction document; SOURCE_URL=https://echa.europa.eu/; SUBSOURCE_URL=https://echa.europa.eu/registration-dossier/-/registered-dossier/22562/7/6/2?documentUUID=62c6f81b-e4db-4e99-8e98-f7a3329411b2; YEAR=2010; ORIGINAL_YEAR=2010; STUDY_GROUP=ECHA IUCLID:15844241:M:--; QC_CATEGORY=Programmatically extracted from structured data source; Source overall passed QC, and this record was expert reviewed; QC_STATUS=pass; SOURCE_HASH=ToxValhc_a30d134ea81113df18b9e4213c3c3223

ToxValDB_GESTIS_DNEL 1 endpoint

Source	Endpoint Type	Value	Unit	Species	Route	Duration	Study Type	Reference
ToxValDB_GESTIS_DNEL	DNEL systemic	=0.23	mg/m3	Human	inhalation	-	Toxicity Value	STORED_SOURCE_RECORD=https://clowder.edap-cluster.com/files/6543dd69e4b045b9ff7cd87e; RECORD_SOURCE_LEVEL=Extraction document; SOURCE_URL=https://www.dguv.de/ifa/gestis/gestis-dnel-liste/index-2.jsp; STUDY_GROUP=GESTIS DNEL:15634099:-:--; QC_CATEGORY=Programmatically extracted from structured data source; Source overall passed QC, but this record was not manually checked; QC_STATUS=not determined; SOURCE_HASH=ToxValhc_50d6e807e662de5ae757a030dfba488a

ToxValDB_PPRTV_(CPHEA) 2 endpoints

Source	Endpoint Type	Value	Unit	Species	Route	Duration	Study Type	Reference
ToxValDB_PPRTV_(CPHEA)	BMDL (HED)	=0.96	mg/kg bw/day	Rat	oral	subchronic; 13 weeks	subchronic	LONG_REF=Toxicol Laboratories, Limited, . (1995). Paraphenylenedianitne: 13 week oral (Gavage) toxicity study in the rat - Volume I and II. (LRL/44/94). Ledbury, England.; AUTHOR=Toxicol Laboratories, Limited,; STORED_SOURCE_RECORD=https://clowder.edap-cluster.com/files/640754fce4b08a6b3934bd22; RECORD_SOURCE_LEVEL=Extraction document; SOURCE_URL=https://www.epa.gov/pprtv/basic-information-about-provisional-peer-reviewed-toxicity-values-pprtvs; SUBSOURCE_URL=https://cfpub.epa.gov/ncea/pprtv/chemicalLanding.cfm?pprtv_sub_id=1850; TOXICOLOGICAL_EFFECT=increased relative liver weight; TOXICOLOGICAL_EFFECT_CATEGORY=organ weight; STUDY_GROUP=PPRTV (CPHEA):15653765:F:--; QC_CATEGORY=Manually extracted from unstructured data source; Source overall passed QC, and this record was manually checked; QC_STATUS=pass; SOURCE_HASH=ToxValhc_00d508b9461406cc18a585b222203a0f
ToxValDB_PPRTV_(CPHEA)	RfD (provisional)	=0.001	mg/kg bw/day	Human	oral	-	Toxicity Value	LONG_REF=Toxicol Laboratories, Limited, . (1995). Paraphenylenedianitne: 13 week oral (Gavage) toxicity study in the rat - Volume I and II. (LRL/44/94). Ledbury, England.; AUTHOR=Toxicol Laboratories, Limited,; STORED_SOURCE_RECORD=https://clowder.edap-cluster.com/files/640754fce4b08a6b3934bd22; RECORD_SOURCE_LEVEL=Extraction document; SOURCE_URL=https://www.epa.gov/pprtv/basic-information-about-provisional-peer-reviewed-toxicity-values-pprtvs; SUBSOURCE_URL=https://cfpub.epa.gov/ncea/pprtv/chemicalLanding.cfm?pprtv_sub_id=1850; TOXICOLOGICAL_EFFECT=increased relative liver weight in female rats; STUDY_GROUP=PPRTV (CPHEA):15653326:-:--; QC_CATEGORY=Manually extracted from unstructured data source; Source overall passed QC, and this record was manually checked; QC_STATUS=pass; SOURCE_HASH=ToxValhc_25112d867c1c5f5985141b8a658b212d

ToxValDB_RSL 1 endpoint

Source	Endpoint Type	Value	Unit	Species	Route	Duration	Study Type	Reference
ToxValDB_RSL	RfD	=0.01	mg/kg bw/day	Human	oral	-	Toxicity Value	STORED_SOURCE_RECORD=https://clowder.edap-cluster.com/files/6759b87ce4b0a7c65d37b4e2; RECORD_SOURCE_LEVEL=Extraction document; SOURCE_URL=https://www.epa.gov/risk/regional-screening-levels-rsls-generic-tables; STUDY_GROUP=RSL:15663671:-:--; QC_CATEGORY=Programmatically extracted from structured data source; Source overall passed QC, but this record was not manually checked; QC_STATUS=not determined; SOURCE_HASH=ToxValhc_06a952912d0ca8e0e3aaa3d47dab4f33

UnifiedCodex:SCCNFP:beta.noael_studies 10 endpoints

Source	Endpoint Type	Value	Unit	Species	Route	Duration	Study Type	Reference
UnifiedCodex:SCCNFP:beta.noael_studies	-	4	mg/kg/day	rat	oral	12-week	-	SOURCE_SUBDIR=out156_en; REPORT_TITLE=OPINION OF THE SCIENTIFIC COMMITTEE ON COSMETIC PRODUCTS AND NON-FOOD PRODUCTS INTENDED FOR CONSUMERS CONCERNING P-PHENYLENEDIAMINE Colipa n° A7; OPINION_NUMBER=SCCNFP/0129/99; COMMITTEE=SCCNFP; REPORT_DATE=27 February 2002; VALUE_TEXT=4; DOSE=-related liver weights were significantly increased for males given 8 mg/kg/day and 16 mg/kg/day.; EFFECT=-related liver weights were significantly increased for males given 8 mg/kg/day and 16 mg/kg/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 NOAEL of PPD was established at 4 mg/kg/day. Ref. : 121 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/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 k; CITATION=Ref. : 121 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; CITATION_NUMBERS=[121,12,344,10,11]; REFERENCE=Ref. : 121 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; DETAILS_JSON={"cas_number":"106-50-3","citation":"Ref. : 121 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","dose":"-related liver weights were significantly increased for males given 8 mg/kg/day and 16 mg/kg/day.","duration":"12-week","effect":"-related liver weights were significantly increased for males given 8 mg/kg/day and 16 mg/kg/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 NOAEL of PPD was established at 4 mg/kg/day. Ref. : 121 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/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 k","endpoint":"","ingredient":"codes","loael_value":"","noael_unit":"mg/kg/day","noael_value":"4","page":6,"route":"oral","species":"rat","study_id":"out156_en_noael_002"}
UnifiedCodex:SCCNFP:beta.noael_studies	-	50	mg/kg bw	rat	oral	13-week	-	SOURCE_SUBDIR=out156_en; REPORT_TITLE=OPINION OF THE SCIENTIFIC COMMITTEE ON COSMETIC PRODUCTS AND NON-FOOD PRODUCTS INTENDED FOR CONSUMERS CONCERNING P-PHENYLENEDIAMINE Colipa n° A7; OPINION_NUMBER=SCCNFP/0129/99; COMMITTEE=SCCNFP; REPORT_DATE=27 February 2002; VALUE_TEXT=50; DOSE=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/day respectively).; EFFECT=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/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. Fo; 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":"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/day respectively).","duration":"13-week","effect":"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/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. Fo","endpoint":"","ingredient":"codes","loael_value":"","noael_unit":"mg/kg bw","noael_value":"50","page":6,"route":"oral","species":"rat","study_id":"out156_en_noael_003"}
UnifiedCodex:SCCNFP:beta.noael_studies	-	4	mg/kg bw	-	-	-	-	SOURCE_SUBDIR=out156_en; REPORT_TITLE=OPINION OF THE SCIENTIFIC COMMITTEE ON COSMETIC PRODUCTS AND NON-FOOD PRODUCTS INTENDED FOR CONSUMERS CONCERNING P-PHENYLENEDIAMINE Colipa n° A7; OPINION_NUMBER=SCCNFP/0129/99; COMMITTEE=SCCNFP; REPORT_DATE=27 February 2002; VALUE_TEXT=4; DOSE=No observed adverse effect level (mg/kg) (species, route of application) \| NOAEL \| = \| 4 mg/kg bw; EFFECT=CALCULATION OF THE MARGIN OF SAFETY (p-PHENYLENEDIAMINE) (Oxidative): No observed adverse effect level (mg/kg) (species, route of application) \| NOAEL \| = \| 4 mg/kg bw; CITATION_NUMBERS=[]; DETAILS_JSON={"cas_number":"106-50-3","citation":"","dose":"No observed adverse effect level (mg/kg) (species, route of application) \| NOAEL \| = \| 4 mg/kg bw","duration":"","effect":"CALCULATION OF THE MARGIN OF SAFETY (p-PHENYLENEDIAMINE) (Oxidative): No observed adverse effect level (mg/kg) (species, route of application) \| NOAEL \| = \| 4 mg/kg bw","endpoint":"","ingredient":"codes","loael_value":"","noael_unit":"mg/kg bw","noael_value":"4","page":24,"route":"","species":"","study_id":"out156_en_noael_010"}
UnifiedCodex:SCCNFP:beta.noael_studies	irritation	=4	mg/kg bw	human	-	-	irritation	SOURCE_SUBDIR=out156_en; REPORT_TITLE=OPINION OF THE SCIENTIFIC COMMITTEE ON COSMETIC PRODUCTS AND NON-FOOD PRODUCTS INTENDED FOR CONSUMERS CONCERNING P-PHENYLENEDIAMINE Colipa n° A7; OPINION_NUMBER=SCCNFP/0129/99; COMMITTEE=SCCNFP; REPORT_DATE=27 February 2002; VALUE_TEXT== 4; DOSE=Thus the usage volume of 100 ml contains at maximum 2.0 % Highest penetration PA (g/cm2) = 4.47 g/cm2 Typical body weight of human = 60 kg Exposed area (scalp) = 700 cm2 Systemic exposure PA x 700 cm2 = 3.129 mg Systemic exposure dose (SED) PA x 700/ 60 x 1000 = 0.052 mg/kg bw No observed adverse effect level (mg/kg) NOAEL = 4 mg/kg bw (specie...; EFFECT=_______________________________________________________ 24 2.11. Safety evaluation CALCULATION OF THE MARGIN OF SAFETY (p-PHENYLENEDIAMINE) (Oxidative) The maximum concentration of 4.0 % of p-Phenylenediamine is mixed before use with H2O2. Thus the usage volume of 100 ml contains at maximum 2.0 % Highest penetration PA (g/cm2) = 4.47 g/cm2 Typical body weight of human = 60 kg Exposed area (scalp) = 700 cm2 Systemic exposure PA x 700 cm2 = 3.129 mg Systemic exposure dose (SED) PA x 700/ 60 x 1000 = 0.052 mg/kg bw No observed adverse effect level (mg/kg) NOAEL = 4 mg/kg bw (species, route of application) Margin of Safety : NOAEL / SED = 77 2.12. Conclusions PPD is used as an oxidising colouring agent for hair dyeing up to a maximum permitted concentration of 4% (free base) in the finished (marketed) cosmetic product. However, in combination with hydrogen peroxide, the maximum use concentration upon application is 2% (free base). * PPD was not irritant or corrosive for the skin and the eye when applied in a 2.5% aqueous solution. * PPD is a strong contact a; CITATION_NUMBERS=[]; DETAILS_JSON={"cas_number":"106-50-3","citation":"","dose":"Thus the usage volume of 100 ml contains at maximum 2.0 % Highest penetration PA (\u0001g/cm2) = 4.47 \u0001g/cm2 Typical body weight of human = 60 kg Exposed area (scalp) = 700 cm2 Systemic exposure PA x 700 cm2 = 3.129 mg Systemic exposure dose (SED) PA x 700/ 60 x 1000 = 0.052 mg/kg bw No observed adverse effect level (mg/kg) NOAEL = 4 mg/kg bw (specie...","duration":"","effect":"_______________________________________________________ 24 2.11. Safety evaluation CALCULATION OF THE MARGIN OF SAFETY (p-PHENYLENEDIAMINE) (Oxidative) The maximum concentration of 4.0 % of p-Phenylenediamine is mixed before use with H2O2. Thus the usage volume of 100 ml contains at maximum 2.0 % Highest penetration PA (\u0001g/cm2) = 4.47 \u0001g/cm2 Typical body weight of human = 60 kg Exposed area (scalp) = 700 cm2 Systemic exposure PA x 700 cm2 = 3.129 mg Systemic exposure dose (SED) PA x 700/ 60 x 1000 = 0.052 mg/kg bw No observed adverse effect level (mg/kg) NOAEL = 4 mg/kg bw (species, route of application) Margin of Safety : NOAEL / SED = 77 2.12. Conclusions PPD is used as an oxidising colouring agent for hair dyeing up to a maximum permitted concentration of 4% (free base) in the finished (marketed) cosmetic product. However, in combination with hydrogen peroxide, the maximum use concentration upon application is 2% (free base). * PPD was not irritant or corrosive for the skin and the eye when applied in a 2.5% aqueous solution. * PPD is a strong contact a","endpoint":"irritation","ingredient":"codes","loael_value":"","noael_unit":"mg/kg bw","noael_value":"= 4","page":24,"route":"","species":"human","study_id":"out156_en_noael_006"}
UnifiedCodex:SCCNFP:beta.noael_studies	irritation	=4	mg/kg bw	human	-	-	irritation	SOURCE_SUBDIR=out156_en; REPORT_TITLE=OPINION OF THE SCIENTIFIC COMMITTEE ON COSMETIC PRODUCTS AND NON-FOOD PRODUCTS INTENDED FOR CONSUMERS CONCERNING P-PHENYLENEDIAMINE Colipa n° A7; OPINION_NUMBER=SCCNFP/0129/99; COMMITTEE=SCCNFP; REPORT_DATE=27 February 2002; VALUE_TEXT== 4; DOSE=Thus the usage volume of 100 ml contains at maximum 2.0 % Highest penetration PA (g/cm2) = 4.47 g/cm2 Typical body weight of human = 60 kg Exposed area (scalp) = 700 cm2 Systemic exposure PA x 700 cm2 = 3.129 mg Systemic exposure dose (SED) PA x 700/ 60 x 1000 = 0.052 mg/kg bw No observed adverse effect level (mg/kg) NOAEL = 4 mg/kg bw (specie...; EFFECT=______________ 24 2.11. Safety evaluation CALCULATION OF THE MARGIN OF SAFETY (p-PHENYLENEDIAMINE) (Oxidative) The maximum concentration of 4.0 % of p-Phenylenediamine is mixed before use with H2O2. Thus the usage volume of 100 ml contains at maximum 2.0 % Highest penetration PA (g/cm2) = 4.47 g/cm2 Typical body weight of human = 60 kg Exposed area (scalp) = 700 cm2 Systemic exposure PA x 700 cm2 = 3.129 mg Systemic exposure dose (SED) PA x 700/ 60 x 1000 = 0.052 mg/kg bw No observed adverse effect level (mg/kg) NOAEL = 4 mg/kg bw (species, route of application) Margin of Safety : NOAEL / SED = 77 2.12. Conclusions PPD is used as an oxidising colouring agent for hair dyeing up to a maximum permitted concentration of 4% (free base) in the finished (marketed) cosmetic product. However, in combination with hydrogen peroxide, the maximum use concentration upon application is 2% (free base). * PPD was not irritant or corrosive for the skin and the eye when applied in a 2.5% aqueous solution. * PPD is a strong contact allergen, both; CITATION_NUMBERS=[]; DETAILS_JSON={"cas_number":"106-50-3","citation":"","dose":"Thus the usage volume of 100 ml contains at maximum 2.0 % Highest penetration PA (\u0001g/cm2) = 4.47 \u0001g/cm2 Typical body weight of human = 60 kg Exposed area (scalp) = 700 cm2 Systemic exposure PA x 700 cm2 = 3.129 mg Systemic exposure dose (SED) PA x 700/ 60 x 1000 = 0.052 mg/kg bw No observed adverse effect level (mg/kg) NOAEL = 4 mg/kg bw (specie...","duration":"","effect":"______________ 24 2.11. Safety evaluation CALCULATION OF THE MARGIN OF SAFETY (p-PHENYLENEDIAMINE) (Oxidative) The maximum concentration of 4.0 % of p-Phenylenediamine is mixed before use with H2O2. Thus the usage volume of 100 ml contains at maximum 2.0 % Highest penetration PA (\u0001g/cm2) = 4.47 \u0001g/cm2 Typical body weight of human = 60 kg Exposed area (scalp) = 700 cm2 Systemic exposure PA x 700 cm2 = 3.129 mg Systemic exposure dose (SED) PA x 700/ 60 x 1000 = 0.052 mg/kg bw No observed adverse effect level (mg/kg) NOAEL = 4 mg/kg bw (species, route of application) Margin of Safety : NOAEL / SED = 77 2.12. Conclusions PPD is used as an oxidising colouring agent for hair dyeing up to a maximum permitted concentration of 4% (free base) in the finished (marketed) cosmetic product. However, in combination with hydrogen peroxide, the maximum use concentration upon application is 2% (free base). * PPD was not irritant or corrosive for the skin and the eye when applied in a 2.5% aqueous solution. * PPD is a strong contact allergen, both","endpoint":"irritation","ingredient":"codes","loael_value":"","noael_unit":"mg/kg bw","noael_value":"= 4","page":24,"route":"","species":"human","study_id":"out156_en_noael_007"}
UnifiedCodex:SCCNFP:beta.noael_studies	irritation	4	%	human	-	-	irritation	SOURCE_SUBDIR=out156_en; REPORT_TITLE=OPINION OF THE SCIENTIFIC COMMITTEE ON COSMETIC PRODUCTS AND NON-FOOD PRODUCTS INTENDED FOR CONSUMERS CONCERNING P-PHENYLENEDIAMINE Colipa n° A7; OPINION_NUMBER=SCCNFP/0129/99; COMMITTEE=SCCNFP; REPORT_DATE=27 February 2002; VALUE_TEXT=4; DOSE=Thus the usage volume of 100 ml contains at maximum 2.0 % Highest penetration PA (g/cm2) = 4.47 g/cm2 Typical body weight of human = 60 kg Exposed area (scalp) = 700 cm2 Systemic exposure PA x 700 cm2 = 3.129 mg Systemic exposure dose (SED) PA x 700/ 60 x 1000 = 0.052 mg/kg bw No observed adverse effect level (mg/kg) NOAEL = 4 mg/kg bw (specie...; EFFECT=SAFETY (p-PHENYLENEDIAMINE) (Oxidative) The maximum concentration of 4.0 % of p-Phenylenediamine is mixed before use with H2O2. Thus the usage volume of 100 ml contains at maximum 2.0 % Highest penetration PA (g/cm2) = 4.47 g/cm2 Typical body weight of human = 60 kg Exposed area (scalp) = 700 cm2 Systemic exposure PA x 700 cm2 = 3.129 mg Systemic exposure dose (SED) PA x 700/ 60 x 1000 = 0.052 mg/kg bw No observed adverse effect level (mg/kg) NOAEL = 4 mg/kg bw (species, route of application) Margin of Safety : NOAEL / SED = 77 2.12. Conclusions PPD is used as an oxidising colouring agent for hair dyeing up to a maximum permitted concentration of 4% (free base) in the finished (marketed) cosmetic product. However, in combination with hydrogen peroxide, the maximum use concentration upon application is 2% (free base). * PPD was not irritant or corrosive for the skin and the eye when applied in a 2.5% aqueous solution. * PPD is a strong contact allergen, both experimentally and in clinical experience. * Several studies on system; CITATION_NUMBERS=[]; DETAILS_JSON={"cas_number":"106-50-3","citation":"","dose":"Thus the usage volume of 100 ml contains at maximum 2.0 % Highest penetration PA (\u0001g/cm2) = 4.47 \u0001g/cm2 Typical body weight of human = 60 kg Exposed area (scalp) = 700 cm2 Systemic exposure PA x 700 cm2 = 3.129 mg Systemic exposure dose (SED) PA x 700/ 60 x 1000 = 0.052 mg/kg bw No observed adverse effect level (mg/kg) NOAEL = 4 mg/kg bw (specie...","duration":"","effect":"SAFETY (p-PHENYLENEDIAMINE) (Oxidative) The maximum concentration of 4.0 % of p-Phenylenediamine is mixed before use with H2O2. Thus the usage volume of 100 ml contains at maximum 2.0 % Highest penetration PA (\u0001g/cm2) = 4.47 \u0001g/cm2 Typical body weight of human = 60 kg Exposed area (scalp) = 700 cm2 Systemic exposure PA x 700 cm2 = 3.129 mg Systemic exposure dose (SED) PA x 700/ 60 x 1000 = 0.052 mg/kg bw No observed adverse effect level (mg/kg) NOAEL = 4 mg/kg bw (species, route of application) Margin of Safety : NOAEL / SED = 77 2.12. Conclusions PPD is used as an oxidising colouring agent for hair dyeing up to a maximum permitted concentration of 4% (free base) in the finished (marketed) cosmetic product. However, in combination with hydrogen peroxide, the maximum use concentration upon application is 2% (free base). * PPD was not irritant or corrosive for the skin and the eye when applied in a 2.5% aqueous solution. * PPD is a strong contact allergen, both experimentally and in clinical experience. * Several studies on system","endpoint":"irritation","ingredient":"codes","loael_value":"","noael_unit":"%","noael_value":"4","page":24,"route":"","species":"human","study_id":"out156_en_noael_008"}
UnifiedCodex:SCCNFP:beta.noael_studies	repeated dose toxicity	5	mg/kg bw/day	rat	oral	Sub-chronic	repeated dose toxicity	SOURCE_SUBDIR=out156_en; REPORT_TITLE=OPINION OF THE SCIENTIFIC COMMITTEE ON COSMETIC PRODUCTS AND NON-FOOD PRODUCTS INTENDED FOR CONSUMERS CONCERNING P-PHENYLENEDIAMINE Colipa n° A7; OPINION_NUMBER=SCCNFP/0129/99; COMMITTEE=SCCNFP; REPORT_DATE=27 February 2002; VALUE_TEXT=5; DOSE=blood chemistry changes resulted in both sexes at dose level of 5 mg/kg/day or greater (increased lactate dehydrogenase and creatine phosphokinase levels). - 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 t...; EFFECT=blood chemistry changes resulted in both sexes at dose level of 5 mg/kg/day or greater (increased lactate dehydrogenase and creatine phosphokinase levels). - 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 NOAEL was 5 mg/kg bw/day. Ref. : 120 2.3.3. Sub-chronic 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 guideline N° 408 (1981). PPD was administered by gavage at corresponding dose levels of 2, 4, 8 and 16 mg/kg/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 twice daily for mortality/viability and once daily for clinical signs; CITATION=Ref. : 120 2; CITATION_NUMBERS=[120,2]; REFERENCE=Ref. : 120 2; DETAILS_JSON={"cas_number":"106-50-3","citation":"Ref. : 120 2","dose":"blood chemistry changes resulted in both sexes at dose level of 5 mg/kg/day or greater (increased lactate dehydrogenase and creatine phosphokinase levels). - 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 t...","duration":"Sub-chronic","effect":"blood chemistry changes resulted in both sexes at dose level of 5 mg/kg/day or greater (increased lactate dehydrogenase and creatine phosphokinase levels). - 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 NOAEL was \u0001 5 mg/kg bw/day. Ref. : 120 2.3.3. Sub-chronic 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 guideline N° 408 (1981). PPD was administered by gavage at corresponding dose levels of 2, 4, 8 and 16 mg/kg/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 twice daily for mortality/viability and once daily for clinical signs","endpoint":"repeated dose toxicity","ingredient":"codes","loael_value":"","noael_unit":"mg/kg bw/day","noael_value":"5","page":5,"route":"oral","species":"rat","study_id":"out156_en_noael_001"}
UnifiedCodex:SCCNFP:beta.noael_studies	repeated dose toxicity	8	mg/kg	rabbit	dermal	13weeks	repeated dose toxicity	SOURCE_SUBDIR=out156_en; REPORT_TITLE=OPINION OF THE SCIENTIFIC COMMITTEE ON COSMETIC PRODUCTS AND NON-FOOD PRODUCTS INTENDED FOR CONSUMERS CONCERNING P-PHENYLENEDIAMINE Colipa n° A7; OPINION_NUMBER=SCCNFP/0129/99; COMMITTEE=SCCNFP; REPORT_DATE=27 February 2002; VALUE_TEXT=8; DOSE=Food intake and body weight gain of treated group were similar to the controls.; EFFECT=y evaluations were conducted before and after 4, 8 and 13weeks of dosing according to a test battery consisting in motor activity and functional battery assessments. There were no mortalities or clinical signs considered related to the test article. Food intake and body weight gain of treated group were similar to the controls. Neuropathology evaluations did not reveal abnormalities within the nervous system or skeletal muscle. There was no effect of the test substance on ocular tissue. Based on these results, the NOEL was 8 mg/kg for both sexes and since the modifications observed can be assumed referring to pharmacological responses and not to neurotoxicity, the NOAEL was 16 mg/kg bw. Ref. : 47 2.3.4. Sub-chronic 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 and other hair-dye constituents were mixed with an equal volume of 6 % hydrogen peroxide. A dose of 1; CITATION=Ref. : 47 2; CITATION_NUMBERS=[47,2]; REFERENCE=Ref. : 47 2; DETAILS_JSON={"cas_number":"106-50-3","citation":"Ref. : 47 2","dose":"Food intake and body weight gain of treated group were similar to the controls.","duration":"13weeks","effect":"y evaluations were conducted before and after 4, 8 and 13weeks of dosing according to a test battery consisting in motor activity and functional battery assessments. There were no mortalities or clinical signs considered related to the test article. Food intake and body weight gain of treated group were similar to the controls. Neuropathology evaluations did not reveal abnormalities within the nervous system or skeletal muscle. There was no effect of the test substance on ocular tissue. Based on these results, the NOEL was 8 mg/kg for both sexes and since the modifications observed can be assumed referring to pharmacological responses and not to neurotoxicity, the NOAEL was 16 mg/kg bw. Ref. : 47 2.3.4. Sub-chronic 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 and other hair-dye constituents were mixed with an equal volume of 6 % hydrogen peroxide. A dose of 1","endpoint":"repeated dose toxicity","ingredient":"codes","loael_value":"","noael_unit":"mg/kg","noael_value":"8","page":6,"route":"dermal","species":"rabbit","study_id":"out156_en_noael_004"}
UnifiedCodex:SCCNFP:beta.noael_studies	repeated dose toxicity	16	mg/kg bw	rabbit	dermal	Sub-chronic	repeated dose toxicity	SOURCE_SUBDIR=out156_en; REPORT_TITLE=OPINION OF THE SCIENTIFIC COMMITTEE ON COSMETIC PRODUCTS AND NON-FOOD PRODUCTS INTENDED FOR CONSUMERS CONCERNING P-PHENYLENEDIAMINE Colipa n° A7; OPINION_NUMBER=SCCNFP/0129/99; COMMITTEE=SCCNFP; REPORT_DATE=27 February 2002; VALUE_TEXT=16; DOSE=Food intake and body weight gain of treated group were similar to the controls.; EFFECT=assessments. There were no mortalities or clinical signs considered related to the test article. Food intake and body weight gain of treated group were similar to the controls. Neuropathology evaluations did not reveal abnormalities within the nervous system or skeletal muscle. There was no effect of the test substance on ocular tissue. Based on these results, the NOEL was 8 mg/kg for both sexes and since the modifications observed can be assumed referring to pharmacological responses and not to neurotoxicity, the NOAEL was 16 mg/kg bw. Ref. : 47 2.3.4. Sub-chronic 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 and other hair-dye constituents were mixed with an equal volume of 6 % hydrogen peroxide. A dose of 1; CITATION=Ref. : 47 2; CITATION_NUMBERS=[47,2]; REFERENCE=Ref. : 47 2; DETAILS_JSON={"cas_number":"106-50-3","citation":"Ref. : 47 2","dose":"Food intake and body weight gain of treated group were similar to the controls.","duration":"Sub-chronic","effect":"assessments. There were no mortalities or clinical signs considered related to the test article. Food intake and body weight gain of treated group were similar to the controls. Neuropathology evaluations did not reveal abnormalities within the nervous system or skeletal muscle. There was no effect of the test substance on ocular tissue. Based on these results, the NOEL was 8 mg/kg for both sexes and since the modifications observed can be assumed referring to pharmacological responses and not to neurotoxicity, the NOAEL was 16 mg/kg bw. Ref. : 47 2.3.4. Sub-chronic 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 and other hair-dye constituents were mixed with an equal volume of 6 % hydrogen peroxide. A dose of 1","endpoint":"repeated dose toxicity","ingredient":"codes","loael_value":"","noael_unit":"mg/kg bw","noael_value":"16","page":6,"route":"dermal","species":"rabbit","study_id":"out156_en_noael_005"}
UnifiedCodex:SCCNFP:beta.noael_studies	reproductive toxicity	4	mg/kg bw	rat	oral	90 day	reproductive toxicity	SOURCE_SUBDIR=out156_en; REPORT_TITLE=OPINION OF THE SCIENTIFIC COMMITTEE ON COSMETIC PRODUCTS AND NON-FOOD PRODUCTS INTENDED FOR CONSUMERS CONCERNING P-PHENYLENEDIAMINE Colipa n° A7; OPINION_NUMBER=SCCNFP/0129/99; COMMITTEE=SCCNFP; REPORT_DATE=27 February 2002; VALUE_TEXT=4; DOSE=drogen peroxide, the maximum use concentration upon application is 2% (free base). * PPD was not irritant or corrosive for the skin and the eye when applied in a 2.5% aqueous solution. * PPD is a strong contact allergen, both experimentally and in clinical experience. * Several studies on systemic toxicity have shown that the most sensitive targ...; EFFECT=drogen peroxide, the maximum use concentration upon application is 2% (free base). * PPD was not irritant or corrosive for the skin and the eye when applied in a 2.5% aqueous solution. * PPD is a strong contact allergen, both experimentally and in clinical experience. * Several studies on systemic toxicity have shown that the most sensitive target organ is skeletal muscle, with a rhabdomyolysis being experimentally observed following oral application in the rat at levels down to 10 mg/kg bw. From a 90 day study, a NOAEL of 4 mg/kg bw was obtained and is used as the basis for the safety evaluation. Reproductive toxicity studies clearly; CITATION_NUMBERS=[]; DETAILS_JSON={"cas_number":"106-50-3","citation":"","dose":"drogen peroxide, the maximum use concentration upon application is 2% (free base). * PPD was not irritant or corrosive for the skin and the eye when applied in a 2.5% aqueous solution. * PPD is a strong contact allergen, both experimentally and in clinical experience. * Several studies on systemic toxicity have shown that the most sensitive targ...","duration":"90 day","effect":"drogen peroxide, the maximum use concentration upon application is 2% (free base). * PPD was not irritant or corrosive for the skin and the eye when applied in a 2.5% aqueous solution. * PPD is a strong contact allergen, both experimentally and in clinical experience. * Several studies on systemic toxicity have shown that the most sensitive target organ is skeletal muscle, with a rhabdomyolysis being experimentally observed following oral application in the rat at levels down to 10 mg/kg bw. From a 90 day study, a NOAEL of 4 mg/kg bw was obtained and is used as the basis for the safety evaluation. Reproductive toxicity studies clearly","endpoint":"reproductive toxicity","ingredient":"codes","loael_value":"","noael_unit":"mg/kg bw","noael_value":"4","page":24,"route":"oral","species":"rat","study_id":"out156_en_noael_009"}

UnifiedCodex:SCCS_SHADOW:beta.noael_studies 81 endpoints

Source	Endpoint Type	Value	Unit	Species	Route	Duration	Study Type	Reference
UnifiedCodex:SCCS_SHADOW:beta.noael_studies	-	<5	mg/kg bw/day	-	-	-	-	SOURCE_SUBDIR=sccp_o_069; REPORT_TITLE=Opinion on p-Phenylenediamine COLIPA N° A7; OPINION_NUMBER=SCCP/0989/06; COMMITTEE=Scientific Committee on Consumer Products (SCCP); REPORT_DATE=10 October 2006; VALUE_TEXT=< 5; DOSE=blood chemistry changes resulted in both sexes at dose level of 5 mg/kg/day or greater (increased lactate dehydrogenase and creatine phosphokinase levels). - 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 t...; EFFECT=blood chemistry changes resulted in both sexes at dose level of 5 mg/kg/day or greater (increased lactate dehydrogenase and creatine phosphokinase levels). - 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 NOAEL was < 5 mg/kg bw/day. Ref.: 120; CITATION=Ref.: 120; CITATION_NUMBERS=[120]; REFERENCE=Ref.: 120; DETAILS_JSON={"cas_number":"106-50-3","citation":"Ref.: 120","dose":"blood chemistry changes resulted in both sexes at dose level of 5 mg/kg/day or greater (increased lactate dehydrogenase and creatine phosphokinase levels). - 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 t...","duration":"","effect":"blood chemistry changes resulted in both sexes at dose level of 5 mg/kg/day or greater (increased lactate dehydrogenase and creatine phosphokinase levels). - 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 NOAEL was < 5 mg/kg bw/day. Ref.: 120","endpoint":"","ingredient":"p-Phenylenediamine (INCI)","loael_value":"","noael_unit":"mg/kg bw/day","noael_value":"< 5","page":13,"route":"","species":"","study_id":"sccp_o_069_noael_001"}
UnifiedCodex:SCCS_SHADOW:beta.noael_studies	-	16	mg/kg bw	rat	oral	12-week	-	SOURCE_SUBDIR=sccp_o_069; REPORT_TITLE=Opinion on p-Phenylenediamine COLIPA N° A7; OPINION_NUMBER=SCCP/0989/06; COMMITTEE=Scientific Committee on Consumer Products (SCCP); REPORT_DATE=10 October 2006; VALUE_TEXT=16; DOSE=-related liver weights were significantly increased for males given 8 mg/kg/day and 16 mg/kg/day.; EFFECT=-related liver weights were significantly increased for males given 8 mg/kg/day and 16 mg/kg/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 NOAEL of PPD was established at 4 mg/kg/day. Ref.: 121 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/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; CITATION=Ref.: 121 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; CITATION_NUMBERS=[121,12,344,10,11]; REFERENCE=Ref.: 121 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; DETAILS_JSON={"cas_number":"106-50-3","citation":"Ref.: 121 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","dose":"-related liver weights were significantly increased for males given 8 mg/kg/day and 16 mg/kg/day.","duration":"12-week","effect":"-related liver weights were significantly increased for males given 8 mg/kg/day and 16 mg/kg/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 NOAEL of PPD was established at 4 mg/kg/day. Ref.: 121 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/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","endpoint":"","ingredient":"p-Phenylenediamine (INCI)","loael_value":"","noael_unit":"mg/kg bw","noael_value":"16","page":14,"route":"oral","species":"rat","study_id":"sccp_o_069_noael_002"}
UnifiedCodex:SCCS_SHADOW:beta.noael_studies	-	50	mg/kg bw	rat	oral	-	-	SOURCE_SUBDIR=sccp_o_069; REPORT_TITLE=Opinion on p-Phenylenediamine COLIPA N° A7; OPINION_NUMBER=SCCP/0989/06; COMMITTEE=Scientific Committee on Consumer Products (SCCP); REPORT_DATE=10 October 2006; VALUE_TEXT=50; DOSE=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/day respectively).; EFFECT=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/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; CITATION=Ref.: 53; CITATION_NUMBERS=[53]; REFERENCE=Ref.: 53; DETAILS_JSON={"cas_number":"106-50-3","citation":"Ref.: 53","dose":"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/day respectively).","duration":"","effect":"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/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","endpoint":"","ingredient":"p-Phenylenediamine (INCI)","loael_value":"","noael_unit":"mg/kg bw","noael_value":"50","page":14,"route":"oral","species":"rat","study_id":"sccp_o_069_noael_003"}
UnifiedCodex:SCCS_SHADOW:beta.noael_studies	-	8	mg/kg	rabbit	dermal	90 day	-	SOURCE_SUBDIR=sccp_o_069; REPORT_TITLE=Opinion on p-Phenylenediamine COLIPA N° A7; OPINION_NUMBER=SCCP/0989/06; COMMITTEE=Scientific Committee on Consumer Products (SCCP); REPORT_DATE=10 October 2006; 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 for both sexes, the NOAEL was 16 mg/kg bw. Ref.: 46 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 and other hair-dye constituents were mixed with an equal volume of 6% hydrogen peroxide. A dose of 1 ml/kg of this mixture was applied for 1 hour without occlusion to three application sites on six animals of each sex. The application sites were abraded pri; CITATION=Ref.: 46 Dermal toxicity A 90 day study has been carried out in the rabbit with the compound administered dermally twice weekly; CITATION_NUMBERS=[46,90]; REFERENCE=Ref.: 46 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.: 46 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 for both sexes, the NOAEL was 16 mg/kg bw. Ref.: 46 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 and other hair-dye constituents were mixed with an equal volume of 6% hydrogen peroxide. A dose of 1 ml/kg of this mixture was applied for 1 hour without occlusion to three application sites on six animals of each sex. The application sites were abraded pri","endpoint":"","ingredient":"p-Phenylenediamine (INCI)","loael_value":"","noael_unit":"mg/kg","noael_value":"8","page":15,"route":"dermal","species":"rabbit","study_id":"sccp_o_069_noael_004"}
UnifiedCodex:SCCS_SHADOW:beta.noael_studies	-	16	mg/kg bw	rabbit	dermal	90 day	-	SOURCE_SUBDIR=sccp_o_069; REPORT_TITLE=Opinion on p-Phenylenediamine COLIPA N° A7; OPINION_NUMBER=SCCP/0989/06; COMMITTEE=Scientific Committee on Consumer Products (SCCP); REPORT_DATE=10 October 2006; VALUE_TEXT=16; DOSE=Food intake and body weight gain of treated group were similar to the controls.; EFFECT=o 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 for both sexes, the NOAEL was 16 mg/kg bw. Ref.: 46 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 and other hair-dye constituents were mixed with an equal volume of 6% hydrogen peroxide. A dose of 1 ml/kg of this mixture was applied for 1 hour without occlusion to three application sites on six animals of each sex. The application sites were abraded prior to the first dose each week. No dos; CITATION=Ref.: 46 Dermal toxicity A 90 day study has been carried out in the rabbit with the compound administered dermally twice weekly; CITATION_NUMBERS=[46,90]; REFERENCE=Ref.: 46 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.: 46 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":"o 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 for both sexes, the NOAEL was 16 mg/kg bw. Ref.: 46 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 and other hair-dye constituents were mixed with an equal volume of 6% hydrogen peroxide. A dose of 1 ml/kg of this mixture was applied for 1 hour without occlusion to three application sites on six animals of each sex. The application sites were abraded prior to the first dose each week. No dos","endpoint":"","ingredient":"p-Phenylenediamine (INCI)","loael_value":"","noael_unit":"mg/kg bw","noael_value":"16","page":15,"route":"dermal","species":"rabbit","study_id":"sccp_o_069_noael_005"}
UnifiedCodex:SCCS_SHADOW:beta.noael_studies	-	4	mg/kg	rat	oral	90-day	-	SOURCE_SUBDIR=sccp_o_069; REPORT_TITLE=Opinion on p-Phenylenediamine COLIPA N° A7; OPINION_NUMBER=SCCP/0989/06; COMMITTEE=Scientific Committee on Consumer Products (SCCP); REPORT_DATE=10 October 2006; VALUE_TEXT=4.0; DOSE=SCCP/0989/06 Opinion on p-phenylenediamine ____________________________________________________________________________________________ 53 Safety evaluation based on toxicokinetics (taken from dossier) 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/...; EFFECT=SCCP/0989/06 Opinion on p-phenylenediamine ____________________________________________________________________________________________ 53 Safety evaluation based on toxicokinetics (taken from dossier) 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) 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 i; CITATION_NUMBERS=[]; DETAILS_JSON={"cas_number":"106-50-3","citation":"","dose":"SCCP/0989/06 Opinion on p-phenylenediamine ____________________________________________________________________________________________ 53 Safety evaluation based on toxicokinetics (taken from dossier) 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/...","duration":"90-day","effect":"SCCP/0989/06 Opinion on p-phenylenediamine ____________________________________________________________________________________________ 53 Safety evaluation based on toxicokinetics (taken from dossier) 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) 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 i","endpoint":"","ingredient":"p-Phenylenediamine (INCI)","loael_value":"","noael_unit":"mg/kg","noael_value":"4.0","page":53,"route":"oral","species":"rat","study_id":"sccp_o_069_noael_010"}
UnifiedCodex:SCCS_SHADOW:beta.noael_studies	-	2	%	rat	-	-	-	SOURCE_SUBDIR=sccp_o_069; REPORT_TITLE=Opinion on p-Phenylenediamine COLIPA N° A7; OPINION_NUMBER=SCCP/0989/06; COMMITTEE=Scientific Committee on Consumer Products (SCCP); REPORT_DATE=10 October 2006; VALUE_TEXT=2.0; DOSE=Taking into account that the human study was performed under maximal exposure conditions, such as maximal PPD concentration (2.0%), short hair length (2 cm) of the treated subjects and; EFFECT=ifferences for toxicokinetics and toxicodynamics (Reference 14). Therefore, the AUC-based margin of safety for PPD is sufficiently high to conclude that the human systemic exposure from hair dyeing with a dark-shade, PPD-containing oxidative hair dye poses no risk to human health. This view is further supported by the margin of safety on the basis of human and rat Cmax values (45-fold), which gives additional assurance that human systemic exposure from PPD-containing hair dyes is far lower than that in rats at the NOAEL. Taking into account that the human study was performed under maximal exposure conditions, such as maximal PPD concentration (2.0%), short hair length (2 cm) of the treated subjects and; CITATION=(Reference 14); CITATION_NUMBERS=[14]; REFERENCE=(Reference 14); DETAILS_JSON={"cas_number":"106-50-3","citation":"(Reference 14)","dose":"Taking into account that the human study was performed under maximal exposure conditions, such as maximal PPD concentration (2.0%), short hair length (2 cm) of the treated subjects and","duration":"","effect":"ifferences for toxicokinetics and toxicodynamics (Reference 14). Therefore, the AUC-based margin of safety for PPD is sufficiently high to conclude that the human systemic exposure from hair dyeing with a dark-shade, PPD-containing oxidative hair dye poses no risk to human health. This view is further supported by the margin of safety on the basis of human and rat Cmax values (45-fold), which gives additional assurance that human systemic exposure from PPD-containing hair dyes is far lower than that in rats at the NOAEL. Taking into account that the human study was performed under maximal exposure conditions, such as maximal PPD concentration (2.0%), short hair length (2 cm) of the treated subjects and","endpoint":"","ingredient":"p-Phenylenediamine (INCI)","loael_value":"","noael_unit":"%","noael_value":"2.0","page":53,"route":"","species":"rat","study_id":"sccp_o_069_noael_012"}
UnifiedCodex:SCCS_SHADOW:beta.noael_studies	-	16	mg/kg bw	-	-	-	-	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"}
UnifiedCodex:SCCS_SHADOW:beta.noael_studies	-	4	mg/kg bw/day	-	-	-	-	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"}
UnifiedCodex:SCCS_SHADOW:beta.noael_studies	-	4	mg/kg bw/d	-	-	-	-	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"}
UnifiedCodex:SCCS_SHADOW:beta.noael_studies	-	16	mg/kg bw/d	-	-	3 days	-	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"}
UnifiedCodex:SCCS_SHADOW:beta.noael_studies	-	16	mg/kg bw/d	-	-	3 days	-	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"}
UnifiedCodex:SCCS_SHADOW:beta.noael_studies	-	8	mg/kg bw	rat	oral	3 days	-	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"}
UnifiedCodex:SCCS_SHADOW:beta.noael_studies	-	50	mg/kg bw	rat	oral	13-week	-	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"}
UnifiedCodex:SCCS_SHADOW:beta.noael_studies	-	8	mg/kg bw/d	rabbit	dermal	90 day	-	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"}
UnifiedCodex:SCCS_SHADOW:beta.noael_studies	-	16	mg/kg bw/d	rabbit	dermal	90 day	-	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"}
UnifiedCodex:SCCS_SHADOW:beta.noael_studies	-	14	-	rat	-	-	-	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"}
UnifiedCodex:SCCS_SHADOW:beta.noael_studies	-	4	mg/kg bw/d	-	oral	90 days	-	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"}
UnifiedCodex:SCCS_SHADOW:beta.noael_studies	-	4	mg/kg bw/d	-	-	90 days	-	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"}
UnifiedCodex:SCCS_SHADOW:beta.noael_studies	-	4	mg/kg bw/d	-	-	90 days	-	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"}
UnifiedCodex:SCCS_SHADOW:beta.noael_studies	-	16	mg/kg bw/d	-	-	90 days	-	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"}
UnifiedCodex:SCCS_SHADOW:beta.noael_studies	-	4	mg/kg bw/d	-	-	90 days	-	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"}
UnifiedCodex:SCCS_SHADOW:beta.noael_studies	-	4	mg/kg bw/d	-	-	90 days	-	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"}
UnifiedCodex:SCCS_SHADOW:beta.noael_studies	-	4	mg/kg bw/d	rat	oral	90-day	-	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"}
UnifiedCodex:SCCS_SHADOW:beta.noael_studies	-	4	mg/kg bw	rat	oral	90-day	-	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 µgeqhr/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"}
UnifiedCodex:SCCS_SHADOW:beta.noael_studies	-	1	%	rat	oral	-	-	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/gh) 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/gh) 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"}
UnifiedCodex:SCCS_SHADOW:beta.noael_studies	-	1	%	rat	oral	-	-	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"}
UnifiedCodex:SCCS_SHADOW:beta.noael_studies	-	6.45	mg/kg bw	rat	oral	-	-	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"}
UnifiedCodex:SCCS_SHADOW:beta.noael_studies	-	6.45	mg/kg bw	rat	oral	-	-	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"}
UnifiedCodex:SCCS_SHADOW:beta.noael_studies	-	1	%	rat	oral	-	-	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"}
UnifiedCodex:SCCS_SHADOW:beta.noael_studies	-	1	%	rat	oral	-	-	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"}
UnifiedCodex:SCCS_SHADOW:beta.noael_studies	-	1	%	rat	oral	-	-	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"}
UnifiedCodex:SCCS_SHADOW:beta.noael_studies	-	1	%	rat	oral	-	-	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"}
UnifiedCodex:SCCS_SHADOW:beta.noael_studies	-	4	mg/kg bw/d	rat	oral	90 day	-	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"}
UnifiedCodex:SCCS_SHADOW:beta.noael_studies	-	4	mg/kg bw/d	-	-	3 days	-	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"}
UnifiedCodex:SCCS_SHADOW:beta.noael_studies	-	4	mg/kg bw/d	-	-	3 days	-	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"}
UnifiedCodex:SCCS_SHADOW:beta.noael_studies	-	16	mg/kg bw/d	-	-	3 days	-	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"}
UnifiedCodex:SCCS_SHADOW:beta.noael_studies	-	8	mg/kg bw/day	rat	-	-	-	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"}
UnifiedCodex:SCCS_SHADOW:beta.noael_studies	-	61	-	-	oral	-	-	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"}
UnifiedCodex:SCCS_SHADOW:beta.noael_studies	-	61	-	-	oral	-	-	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"}
UnifiedCodex:SCCS_SHADOW:beta.noael_studies	-	61	-	-	oral	-	-	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"}
UnifiedCodex:SCCS_SHADOW:beta.noael_studies	-	61	-	-	oral	-	-	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"}
UnifiedCodex:SCCS_SHADOW:beta.noael_studies	-	61	-	-	oral	-	-	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"}
UnifiedCodex:SCCS_SHADOW:beta.noael_studies	-	61	-	-	oral	-	-	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"}
UnifiedCodex:SCCS_SHADOW:beta.noael_studies	-	61	-	-	oral	-	-	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"}
UnifiedCodex:SCCS_SHADOW:beta.noael_studies	-	61	-	-	oral	-	-	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"}
UnifiedCodex:SCCS_SHADOW:beta.noael_studies	-	4	-	-	oral	-	-	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"}
UnifiedCodex:SCCS_SHADOW:beta.noael_studies	-	8	-	-	oral	-	-	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"}
UnifiedCodex:SCCS_SHADOW:beta.noael_studies	-	16	-	-	oral	-	-	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"}
UnifiedCodex:SCCS_SHADOW:beta.noael_studies	-	50	-	-	oral	-	-	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"}
UnifiedCodex:SCCS_SHADOW:beta.noael_studies	-	4	-	-	oral	-	-	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"}
UnifiedCodex:SCCS_SHADOW:beta.noael_studies	-	8	-	-	oral	-	-	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"}
UnifiedCodex:SCCS_SHADOW:beta.noael_studies	-	16	-	-	oral	-	-	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"}
UnifiedCodex:SCCS_SHADOW:beta.noael_studies	-	50	-	-	oral	-	-	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"}
UnifiedCodex:SCCS_SHADOW:beta.noael_studies	carcinogenicity	4	mg/kg bw	rat	dermal	90 day	carcinogenicity	SOURCE_SUBDIR=sccp_o_069; REPORT_TITLE=Opinion on p-Phenylenediamine COLIPA N° A7; OPINION_NUMBER=SCCP/0989/06; COMMITTEE=Scientific Committee on Consumer Products (SCCP); REPORT_DATE=10 October 2006; VALUE_TEXT=4; DOSE=From a 90 day study, a NOAEL of 4 mg/kg bw was obtained and is used as the basis for the safety evaluation.; EFFECT=ide were tested by topical application as well as by subcutaneous injection of rats. In both studies a statistical significant increase mammary gland tumours were found both after topical application as well as after subcutaneous injection. The studies have been criticized. However, it is not possible to disqualify the studies completely. p-Phenylenediamine together with hydrogen peroxide may be carcinogenic in experimental studies with rats. Safety assessment A Common approach of the SCCP: From a 90 day study, a NOAEL of 4 mg/kg bw was obtained 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 77.; CITATION_NUMBERS=[]; DETAILS_JSON={"cas_number":"106-50-3","citation":"","dose":"From a 90 day study, a NOAEL of 4 mg/kg bw was obtained and is used as the basis for the safety evaluation.","duration":"90 day","effect":"ide were tested by topical application as well as by subcutaneous injection of rats. In both studies a statistical significant increase mammary gland tumours were found both after topical application as well as after subcutaneous injection. The studies have been criticized. However, it is not possible to disqualify the studies completely. p-Phenylenediamine together with hydrogen peroxide may be carcinogenic in experimental studies with rats. Safety assessment A Common approach of the SCCP: From a 90 day study, a NOAEL of 4 mg/kg bw was obtained 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 77.","endpoint":"carcinogenicity","ingredient":"p-Phenylenediamine (INCI)","loael_value":"","noael_unit":"mg/kg bw","noael_value":"4","page":56,"route":"dermal","species":"rat","study_id":"sccp_o_069_noael_016"}
UnifiedCodex:SCCS_SHADOW:beta.noael_studies	carcinogenicity	4	mg/kg	rat	-	-	carcinogenicity	SOURCE_SUBDIR=sccp_o_069; REPORT_TITLE=Opinion on p-Phenylenediamine COLIPA N° A7; OPINION_NUMBER=SCCP/0989/06; COMMITTEE=Scientific Committee on Consumer Products (SCCP); REPORT_DATE=10 October 2006; VALUE_TEXT=4; DOSE=In this approach, the AUC in rats following a peroral dosage of 4 mg/kg (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: on with couplers and /or hydrogen peroxide as well in a carcinogenicity study were reported. ¾ 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 (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. ¾ 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 (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: on with couplers and /or hydrogen peroxide as well in a carcinogenicity study were reported. ¾ 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 (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. ¾ 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":"p-Phenylenediamine (INCI)","loael_value":"","noael_unit":"mg/kg","noael_value":"4","page":57,"route":"","species":"rat","study_id":"sccp_o_069_noael_018"}
UnifiedCodex:SCCS_SHADOW:beta.noael_studies	carcinogenicity	4	mg/kg bw	rat	-	-	carcinogenicity	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"}
UnifiedCodex:SCCS_SHADOW:beta.noael_studies	developmental toxicity	5	mg/kg bw	human	-	developmental	developmental toxicity	SOURCE_SUBDIR=sccp_o_069; REPORT_TITLE=Opinion on p-Phenylenediamine COLIPA N° A7; OPINION_NUMBER=SCCP/0989/06; COMMITTEE=Scientific Committee on Consumer Products (SCCP); REPORT_DATE=10 October 2006; VALUE_TEXT=5; DOSE=SCCP/0989/06 Opinion on p-phenylenediamine ____________________________________________________________________________________________ 46 The NOAEL of maternal toxicity is 5 mg/kg bw whereas the NOAEL of developmental toxicity is 10 mg/kg bw.; EFFECT=SCCP/0989/06 Opinion on p-phenylenediamine ____________________________________________________________________________________________ 46 The NOAEL of maternal toxicity is 5 mg/kg bw whereas the NOAEL of developmental toxicity is 10 mg/kg bw. Ref.: 8, subm. 12/2005 3.3.9. Toxicokinetics Human hepatic metabolism in vitro Guideline: / Cells: human hepatocytes, 4 male donors (cryo-preserved) Test substance: p-phenylenediamine dihydrochloride Sigma-Aldrich P6001 Radiolabeled substance: [14C(u)]-1,4-phenylenediamine dihydrochloride (14C PPD) Specific activity: 33.2 mCi/mmol Batch: Lot No. 10194-57-A Purity: > 98% Test system A hepatocytes (10 µM, 50 µM and 100; CITATION=Ref.: 8, subm; CITATION_NUMBERS=[8]; REFERENCE=Ref.: 8, subm; DETAILS_JSON={"cas_number":"106-50-3","citation":"Ref.: 8, subm","dose":"SCCP/0989/06 Opinion on p-phenylenediamine ____________________________________________________________________________________________ 46 The NOAEL of maternal toxicity is 5 mg/kg bw whereas the NOAEL of developmental toxicity is 10 mg/kg bw.","duration":"developmental","effect":"SCCP/0989/06 Opinion on p-phenylenediamine ____________________________________________________________________________________________ 46 The NOAEL of maternal toxicity is 5 mg/kg bw whereas the NOAEL of developmental toxicity is 10 mg/kg bw. Ref.: 8, subm. 12/2005 3.3.9. Toxicokinetics Human hepatic metabolism in vitro Guideline: / Cells: human hepatocytes, 4 male donors (cryo-preserved) Test substance: p-phenylenediamine dihydrochloride Sigma-Aldrich P6001 Radiolabeled substance: [14C(u)]-1,4-phenylenediamine dihydrochloride (14C PPD) Specific activity: 33.2 mCi/mmol Batch: Lot No. 10194-57-A Purity: > 98% Test system A hepatocytes (10 µM, 50 µM and 100","endpoint":"developmental toxicity","ingredient":"p-Phenylenediamine (INCI)","loael_value":"","noael_unit":"mg/kg bw","noael_value":"5","page":46,"route":"","species":"human","study_id":"sccp_o_069_noael_006"}
UnifiedCodex:SCCS_SHADOW:beta.noael_studies	developmental toxicity	4	mg/kg bw	rat	oral	90 day	developmental toxicity	SOURCE_SUBDIR=sccp_o_069; REPORT_TITLE=Opinion on p-Phenylenediamine COLIPA N° A7; OPINION_NUMBER=SCCP/0989/06; COMMITTEE=Scientific Committee on Consumer Products (SCCP); REPORT_DATE=10 October 2006; VALUE_TEXT=4; DOSE=75 mg/kg died within 3 h.; EFFECT=75 mg/kg died within 3 h. The animal treated with 50 mg/kg bw showed clinical signs (lachrimation, swelling of conjunctivae, gait, tremor, subdued behaviour and/or pilorection). 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 skeletal muscle, with a rhabdomyolysis being experimentally observed following oral application in the rat at levels down to 10 mg/kg bw. From a 90 day study, a NOAEL of 4 mg/kg bw was obtained and is used as the basis for the safety evaluation. In a gavage developmental toxicity study in rats the NOAEL of maternal toxicity is 5 mg/kg bw whereas the NOAEL of developmental toxicity is 10 mg/kg bw. Irritation, sensitisation PPD was not irritant or corrosive for the skin and the eye when applied in a 2.5% aqueous solution. PPD is an extremely potent contact allergen, both experimentally and in clinical experience. Dermal absorption Several relevant studies have been performed o; CITATION_NUMBERS=[]; DETAILS_JSON={"cas_number":"106-50-3","citation":"","dose":"75 mg/kg died within 3 h.","duration":"90 day","effect":"75 mg/kg died within 3 h. The animal treated with 50 mg/kg bw showed clinical signs (lachrimation, swelling of conjunctivae, gait, tremor, subdued behaviour and/or pilorection). 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 skeletal muscle, with a rhabdomyolysis being experimentally observed following oral application in the rat at levels down to 10 mg/kg bw. From a 90 day study, a NOAEL of 4 mg/kg bw was obtained and is used as the basis for the safety evaluation. In a gavage developmental toxicity study in rats the NOAEL of maternal toxicity is 5 mg/kg bw whereas the NOAEL of developmental toxicity is 10 mg/kg bw. Irritation, sensitisation PPD was not irritant or corrosive for the skin and the eye when applied in a 2.5% aqueous solution. PPD is an extremely potent contact allergen, both experimentally and in clinical experience. Dermal absorption Several relevant studies have been performed o","endpoint":"developmental toxicity","ingredient":"p-Phenylenediamine (INCI)","loael_value":"","noael_unit":"mg/kg bw","noael_value":"4","page":54,"route":"oral","species":"rat","study_id":"sccp_o_069_noael_013"}
UnifiedCodex:SCCS_SHADOW:beta.noael_studies	developmental toxicity	5	mg/kg bw	rat	oral	90 day	developmental toxicity	SOURCE_SUBDIR=sccp_o_069; REPORT_TITLE=Opinion on p-Phenylenediamine COLIPA N° A7; OPINION_NUMBER=SCCP/0989/06; COMMITTEE=Scientific Committee on Consumer Products (SCCP); REPORT_DATE=10 October 2006; VALUE_TEXT=5; DOSE=At 25 mg/kg bw only orange traces in the bedding were seen probably due to coloured urine.; EFFECT=subdued behaviour and/or pilorection). 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 skeletal muscle, with a rhabdomyolysis being experimentally observed following oral application in the rat at levels down to 10 mg/kg bw. From a 90 day study, a NOAEL of 4 mg/kg bw was obtained and is used as the basis for the safety evaluation. In a gavage developmental toxicity study in rats the NOAEL of maternal toxicity is 5 mg/kg bw whereas the NOAEL of developmental toxicity is 10 mg/kg bw. Irritation, sensitisation PPD was not irritant or corrosive for the skin and the eye when applied in a 2.5% aqueous solution. PPD is an extremely potent contact allergen, both experimentally and in clinical experience. Dermal absorption Several relevant studies have been performed on percutaneous absorption of PPD. The highest cumulative penetration obtained was 4.47 µg/cm2. Toxicokinetics Two rat studies in vivo show; 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":"subdued behaviour and/or pilorection). 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 skeletal muscle, with a rhabdomyolysis being experimentally observed following oral application in the rat at levels down to 10 mg/kg bw. From a 90 day study, a NOAEL of 4 mg/kg bw was obtained and is used as the basis for the safety evaluation. In a gavage developmental toxicity study in rats the NOAEL of maternal toxicity is 5 mg/kg bw whereas the NOAEL of developmental toxicity is 10 mg/kg bw. Irritation, sensitisation PPD was not irritant or corrosive for the skin and the eye when applied in a 2.5% aqueous solution. PPD is an extremely potent contact allergen, both experimentally and in clinical experience. Dermal absorption Several relevant studies have been performed on percutaneous absorption of PPD. The highest cumulative penetration obtained was 4.47 µg/cm2. Toxicokinetics Two rat studies in vivo show","endpoint":"developmental toxicity","ingredient":"p-Phenylenediamine (INCI)","loael_value":"","noael_unit":"mg/kg bw","noael_value":"5","page":54,"route":"oral","species":"rat","study_id":"sccp_o_069_noael_014"}
UnifiedCodex:SCCS_SHADOW:beta.noael_studies	developmental toxicity	5	mg/kg bw	rat	oral	90 day	developmental toxicity	SOURCE_SUBDIR=sccp_o_069; REPORT_TITLE=Opinion on p-Phenylenediamine COLIPA N° A7; OPINION_NUMBER=SCCP/0989/06; COMMITTEE=Scientific Committee on Consumer Products (SCCP); REPORT_DATE=10 October 2006; VALUE_TEXT=5; DOSE=Several studies on systemic toxicity have shown that the most sensitive target organ is skeletal muscle, with a rhabdomyolysis being experimentally observed following oral application in the rat at levels down to 10 mg/kg bw.; EFFECT=w 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 skeletal muscle, with a rhabdomyolysis being experimentally observed following oral application in the rat at levels down to 10 mg/kg bw. From a 90 day study, a NOAEL of 4 mg/kg bw was obtained and is used as the basis for the safety evaluation. In a gavage developmental toxicity study in rats the NOAEL of maternal toxicity is 5 mg/kg bw whereas the NOAEL of developmental toxicity is 10 mg/kg bw. Irritation, sensitisation PPD was not irritant or corrosive for the skin and the eye when applied in a 2.5% aqueous solution. PPD is an extremely potent contact allergen, both experimentally and in clinical experience. Dermal absorption Several relevant studies have been performed on percutaneous absorption of PPD. The highest cumulative penetration obtained was 4.47 µg/cm2. Toxicokinetics Two rat studies in vivo show that PPD after oral administration is quickly absorb; CITATION_NUMBERS=[]; DETAILS_JSON={"cas_number":"106-50-3","citation":"","dose":"Several studies on systemic toxicity have shown that the most sensitive target organ is skeletal muscle, with a rhabdomyolysis being experimentally observed following oral application in the rat at levels down to 10 mg/kg bw.","duration":"90 day","effect":"w 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 skeletal muscle, with a rhabdomyolysis being experimentally observed following oral application in the rat at levels down to 10 mg/kg bw. From a 90 day study, a NOAEL of 4 mg/kg bw was obtained and is used as the basis for the safety evaluation. In a gavage developmental toxicity study in rats the NOAEL of maternal toxicity is 5 mg/kg bw whereas the NOAEL of developmental toxicity is 10 mg/kg bw. Irritation, sensitisation PPD was not irritant or corrosive for the skin and the eye when applied in a 2.5% aqueous solution. PPD is an extremely potent contact allergen, both experimentally and in clinical experience. Dermal absorption Several relevant studies have been performed on percutaneous absorption of PPD. The highest cumulative penetration obtained was 4.47 µg/cm2. Toxicokinetics Two rat studies in vivo show that PPD after oral administration is quickly absorb","endpoint":"developmental toxicity","ingredient":"p-Phenylenediamine (INCI)","loael_value":"","noael_unit":"mg/kg bw","noael_value":"5","page":54,"route":"oral","species":"rat","study_id":"sccp_o_069_noael_015"}
UnifiedCodex:SCCS_SHADOW:beta.noael_studies	developmental toxicity	5	mg/kg bw/day	rat	oral	3 days	developmental toxicity	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"}
UnifiedCodex:SCCS_SHADOW:beta.noael_studies	developmental toxicity	5	mg/kg bw/day	rat	oral	3 days	developmental toxicity	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"}
UnifiedCodex:SCCS_SHADOW:beta.noael_studies	repeated dose toxicity	=0.052	mg/kg bw	rat	oral	subchronic	repeated dose toxicity	SOURCE_SUBDIR=sccp_o_069; REPORT_TITLE=Opinion on p-Phenylenediamine COLIPA N° A7; OPINION_NUMBER=SCCP/0989/06; COMMITTEE=Scientific Committee on Consumer Products (SCCP); REPORT_DATE=10 October 2006; VALUE_TEXT== 0.052; DOSE=Thus the usage volume of 100 ml contains at maximum 2.0% Highest penetration PA (µg/cm2) = 4.47 µg/cm2 Typical body weight of human = 60 kg Exposed area (scalp) = 700 cm2 Systemic exposure PA x 700 cm2 = 3.129 mg Systemic exposure dose (SED) PA x 700/ 60 x 1000 = 0.052 mg/kg bw No observed adverse effect level (mg/kg) NOAEL = 4 mg/kg bw (rat, or...; EFFECT=(including calculation of the MoS) Taken from SCCNFP/0129/99, adopted in 2002 CALCULATION OF THE MARGIN OF SAFETY (p-PHENYLENEDIAMINE) (Oxidative) The maximum concentration of 4.0% of p-Phenylenediamine is mixed before use with H2O2. Thus the usage volume of 100 ml contains at maximum 2.0% Highest penetration PA (µg/cm2) = 4.47 µg/cm2 Typical body weight of human = 60 kg Exposed area (scalp) = 700 cm2 Systemic exposure PA x 700 cm2 = 3.129 mg Systemic exposure dose (SED) PA x 700/ 60 x 1000 = 0.052 mg/kg bw No observed adverse effect level (mg/kg) NOAEL = 4 mg/kg bw (rat, oral, subchronic toxicity) Margin of Safety NOAEL / SED = 77; CITATION_NUMBERS=[]; DETAILS_JSON={"cas_number":"106-50-3","citation":"","dose":"Thus the usage volume of 100 ml contains at maximum 2.0% Highest penetration PA (µg/cm2) = 4.47 µg/cm2 Typical body weight of human = 60 kg Exposed area (scalp) = 700 cm2 Systemic exposure PA x 700 cm2 = 3.129 mg Systemic exposure dose (SED) PA x 700/ 60 x 1000 = 0.052 mg/kg bw No observed adverse effect level (mg/kg) NOAEL = 4 mg/kg bw (rat, or...","duration":"subchronic","effect":"(including calculation of the MoS) Taken from SCCNFP/0129/99, adopted in 2002 CALCULATION OF THE MARGIN OF SAFETY (p-PHENYLENEDIAMINE) (Oxidative) The maximum concentration of 4.0% of p-Phenylenediamine is mixed before use with H2O2. Thus the usage volume of 100 ml contains at maximum 2.0% Highest penetration PA (µg/cm2) = 4.47 µg/cm2 Typical body weight of human = 60 kg Exposed area (scalp) = 700 cm2 Systemic exposure PA x 700 cm2 = 3.129 mg Systemic exposure dose (SED) PA x 700/ 60 x 1000 = 0.052 mg/kg bw No observed adverse effect level (mg/kg) NOAEL = 4 mg/kg bw (rat, oral, subchronic toxicity) Margin of Safety NOAEL / SED = 77","endpoint":"repeated dose toxicity","ingredient":"p-Phenylenediamine (INCI)","loael_value":"","noael_unit":"mg/kg bw","noael_value":"= 0.052","page":52,"route":"oral","species":"rat","study_id":"sccp_o_069_noael_007"}
UnifiedCodex:SCCS_SHADOW:beta.noael_studies	repeated dose toxicity	=4	mg/kg bw	rat	oral	subchronic	repeated dose toxicity	SOURCE_SUBDIR=sccp_o_069; REPORT_TITLE=Opinion on p-Phenylenediamine COLIPA N° A7; OPINION_NUMBER=SCCP/0989/06; COMMITTEE=Scientific Committee on Consumer Products (SCCP); REPORT_DATE=10 October 2006; VALUE_TEXT== 4; DOSE=Thus the usage volume of 100 ml contains at maximum 2.0% Highest penetration PA (µg/cm2) = 4.47 µg/cm2 Typical body weight of human = 60 kg Exposed area (scalp) = 700 cm2 Systemic exposure PA x 700 cm2 = 3.129 mg Systemic exposure dose (SED) PA x 700/ 60 x 1000 = 0.052 mg/kg bw No observed adverse effect level (mg/kg) NOAEL = 4 mg/kg bw (rat, or...; EFFECT=n from SCCNFP/0129/99, adopted in 2002 CALCULATION OF THE MARGIN OF SAFETY (p-PHENYLENEDIAMINE) (Oxidative) The maximum concentration of 4.0% of p-Phenylenediamine is mixed before use with H2O2. Thus the usage volume of 100 ml contains at maximum 2.0% Highest penetration PA (µg/cm2) = 4.47 µg/cm2 Typical body weight of human = 60 kg Exposed area (scalp) = 700 cm2 Systemic exposure PA x 700 cm2 = 3.129 mg Systemic exposure dose (SED) PA x 700/ 60 x 1000 = 0.052 mg/kg bw No observed adverse effect level (mg/kg) NOAEL = 4 mg/kg bw (rat, oral, subchronic toxicity) Margin of Safety NOAEL / SED = 77; CITATION_NUMBERS=[]; DETAILS_JSON={"cas_number":"106-50-3","citation":"","dose":"Thus the usage volume of 100 ml contains at maximum 2.0% Highest penetration PA (µg/cm2) = 4.47 µg/cm2 Typical body weight of human = 60 kg Exposed area (scalp) = 700 cm2 Systemic exposure PA x 700 cm2 = 3.129 mg Systemic exposure dose (SED) PA x 700/ 60 x 1000 = 0.052 mg/kg bw No observed adverse effect level (mg/kg) NOAEL = 4 mg/kg bw (rat, or...","duration":"subchronic","effect":"n from SCCNFP/0129/99, adopted in 2002 CALCULATION OF THE MARGIN OF SAFETY (p-PHENYLENEDIAMINE) (Oxidative) The maximum concentration of 4.0% of p-Phenylenediamine is mixed before use with H2O2. Thus the usage volume of 100 ml contains at maximum 2.0% Highest penetration PA (µg/cm2) = 4.47 µg/cm2 Typical body weight of human = 60 kg Exposed area (scalp) = 700 cm2 Systemic exposure PA x 700 cm2 = 3.129 mg Systemic exposure dose (SED) PA x 700/ 60 x 1000 = 0.052 mg/kg bw No observed adverse effect level (mg/kg) NOAEL = 4 mg/kg bw (rat, oral, subchronic toxicity) Margin of Safety NOAEL / SED = 77","endpoint":"repeated dose toxicity","ingredient":"p-Phenylenediamine (INCI)","loael_value":"","noael_unit":"mg/kg bw","noael_value":"= 4","page":52,"route":"oral","species":"rat","study_id":"sccp_o_069_noael_008"}
UnifiedCodex:SCCS_SHADOW:beta.noael_studies	repeated dose toxicity	=4	mg/kg bw	rat	oral	subchronic	repeated dose toxicity	SOURCE_SUBDIR=sccp_o_069; REPORT_TITLE=Opinion on p-Phenylenediamine COLIPA N° A7; OPINION_NUMBER=SCCP/0989/06; COMMITTEE=Scientific Committee on Consumer Products (SCCP); REPORT_DATE=10 October 2006; VALUE_TEXT== 4; DOSE=Thus the usage volume of 100 ml contains at maximum 2.0% Highest penetration PA (µg/cm2) = 4.47 µg/cm2 Typical body weight of human = 60 kg Exposed area (scalp) = 700 cm2 Systemic exposure PA x 700 cm2 = 3.129 mg Systemic exposure dose (SED) PA x 700/ 60 x 1000 = 0.052 mg/kg bw No observed adverse effect level (mg/kg) NOAEL = 4 mg/kg bw (rat, or...; EFFECT=AFETY (p-PHENYLENEDIAMINE) (Oxidative) The maximum concentration of 4.0% of p-Phenylenediamine is mixed before use with H2O2. Thus the usage volume of 100 ml contains at maximum 2.0% Highest penetration PA (µg/cm2) = 4.47 µg/cm2 Typical body weight of human = 60 kg Exposed area (scalp) = 700 cm2 Systemic exposure PA x 700 cm2 = 3.129 mg Systemic exposure dose (SED) PA x 700/ 60 x 1000 = 0.052 mg/kg bw No observed adverse effect level (mg/kg) NOAEL = 4 mg/kg bw (rat, oral, subchronic toxicity) Margin of Safety NOAEL / SED = 77; CITATION_NUMBERS=[]; DETAILS_JSON={"cas_number":"106-50-3","citation":"","dose":"Thus the usage volume of 100 ml contains at maximum 2.0% Highest penetration PA (µg/cm2) = 4.47 µg/cm2 Typical body weight of human = 60 kg Exposed area (scalp) = 700 cm2 Systemic exposure PA x 700 cm2 = 3.129 mg Systemic exposure dose (SED) PA x 700/ 60 x 1000 = 0.052 mg/kg bw No observed adverse effect level (mg/kg) NOAEL = 4 mg/kg bw (rat, or...","duration":"subchronic","effect":"AFETY (p-PHENYLENEDIAMINE) (Oxidative) The maximum concentration of 4.0% of p-Phenylenediamine is mixed before use with H2O2. Thus the usage volume of 100 ml contains at maximum 2.0% Highest penetration PA (µg/cm2) = 4.47 µg/cm2 Typical body weight of human = 60 kg Exposed area (scalp) = 700 cm2 Systemic exposure PA x 700 cm2 = 3.129 mg Systemic exposure dose (SED) PA x 700/ 60 x 1000 = 0.052 mg/kg bw No observed adverse effect level (mg/kg) NOAEL = 4 mg/kg bw (rat, oral, subchronic toxicity) Margin of Safety NOAEL / SED = 77","endpoint":"repeated dose toxicity","ingredient":"p-Phenylenediamine (INCI)","loael_value":"","noael_unit":"mg/kg bw","noael_value":"= 4","page":52,"route":"oral","species":"rat","study_id":"sccp_o_069_noael_009"}
UnifiedCodex:SCCS_SHADOW:beta.noael_studies	repeated dose toxicity	4	mg/kg/day	rat	oral	subchronic	repeated dose toxicity	SOURCE_SUBDIR=sccp_o_069; REPORT_TITLE=Opinion on p-Phenylenediamine COLIPA N° A7; OPINION_NUMBER=SCCP/0989/06; COMMITTEE=Scientific Committee on Consumer Products (SCCP); REPORT_DATE=10 October 2006; 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/day) yields a toxicokinetic-based safety margin of 16.3-fold.; EFFECT=xposure 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/day) yields a toxicokinetic-based safety margin of 16.3-fold. Figure 1: Comparison of plasma concentrations ([14C]-PPD µg-eq / ml) in rats after a single dose of 4.0 mg/kg [14C]-PPD with those in human subjects after hair dyeing with a dark shade, 2.0% [14C]-PPD-containing hair dye. 0 2 4 6 8 10 12 14 16 18 20 22 24 0 1000 2000 3000 4000 5000 male rat, single oral dose of 4.0 mg/kg female rat, single oral dose of 4.0 mg/kg man after hair dyeing hours after administ; 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/day) yields a toxicokinetic-based safety margin of 16.3-fold.","duration":"subchronic","effect":"xposure 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/day) yields a toxicokinetic-based safety margin of 16.3-fold. Figure 1: Comparison of plasma concentrations ([14C]-PPD µg-eq / ml) in rats after a single dose of 4.0 mg/kg [14C]-PPD with those in human subjects after hair dyeing with a dark shade, 2.0% [14C]-PPD-containing hair dye. 0 2 4 6 8 10 12 14 16 18 20 22 24 0 1000 2000 3000 4000 5000 male rat, single oral dose of 4.0 mg/kg female rat, single oral dose of 4.0 mg/kg man after hair dyeing hours after administ","endpoint":"repeated dose toxicity","ingredient":"p-Phenylenediamine (INCI)","loael_value":"","noael_unit":"mg/kg/day","noael_value":"4.0","page":53,"route":"oral","species":"rat","study_id":"sccp_o_069_noael_011"}
UnifiedCodex:SCCS_SHADOW:beta.noael_studies	repeated dose toxicity	4	mg/kg/day	rat	oral	subchronic	repeated dose toxicity	SOURCE_SUBDIR=sccp_o_069; REPORT_TITLE=Opinion on p-Phenylenediamine COLIPA N° A7; OPINION_NUMBER=SCCP/0989/06; COMMITTEE=Scientific Committee on Consumer Products (SCCP); REPORT_DATE=10 October 2006; 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/day) yields a toxicokinetic-based safety margin of 16.3-fold.; EFFECT=SCCP/0989/06 Opinion on p-phenylenediamine ____________________________________________________________________________________________ 57 B Toxicokinetic approach: In human volunteers (N=8), hair dyeing with a dark-shade, 2.0% [14C]-PPD-containing hair dye produced 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/day) yields a toxicokinetic-based safety margin of 16.3-fold. Given the AUC figures obtained from rats and humans the 4-fold factor for interspecies differences in toxicokinetics could be set to 1 which results in a remaining safety factor of 25 which was not achieved. 4. CONCLUSION For the final safety assessment of PPD several aspects have to be taken into account: ¾ The SCCP considers PPD alone as being not genotoxic. But, positive findings from genotoxicity s; 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/day) yields a toxicokinetic-based safety margin of 16.3-fold.","duration":"subchronic","effect":"SCCP/0989/06 Opinion on p-phenylenediamine ____________________________________________________________________________________________ 57 B Toxicokinetic approach: In human volunteers (N=8), hair dyeing with a dark-shade, 2.0% [14C]-PPD-containing hair dye produced 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/day) yields a toxicokinetic-based safety margin of 16.3-fold. Given the AUC figures obtained from rats and humans the 4-fold factor for interspecies differences in toxicokinetics could be set to 1 which results in a remaining safety factor of 25 which was not achieved. 4. CONCLUSION For the final safety assessment of PPD several aspects have to be taken into account: ¾ The SCCP considers PPD alone as being not genotoxic. But, positive findings from genotoxicity s","endpoint":"repeated dose toxicity","ingredient":"p-Phenylenediamine (INCI)","loael_value":"","noael_unit":"mg/kg/day","noael_value":"4.0","page":57,"route":"oral","species":"rat","study_id":"sccp_o_069_noael_017"}
UnifiedCodex:SCCS_SHADOW:beta.noael_studies	repeated dose toxicity	<5	mg/kg bw/day	rat	oral	Sub-chronic	repeated dose toxicity	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"}
UnifiedCodex:SCCS_SHADOW:beta.noael_studies	repeated dose toxicity	8	mg/kg bw/d	human	dermal	3 days	repeated dose toxicity	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"}
UnifiedCodex:SCCS_SHADOW:beta.noael_studies	repeated dose toxicity	=0.04	mg/kg bw/d	rat	oral	subchronic	repeated dose toxicity	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"}
UnifiedCodex:SCCS_SHADOW:beta.noael_studies	repeated dose toxicity	=8	mg/kg bw/d	rat	oral	subchronic	repeated dose toxicity	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"}
UnifiedCodex:SCCS_SHADOW:beta.noael_studies	repeated dose toxicity	4	mg/kg bw/day	rat	oral	subchronic	repeated dose toxicity	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 µgeqhr/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"}
UnifiedCodex:SCCS_SHADOW:beta.noael_studies	repeated dose toxicity	8	mg/kg bw/d	rat	-	subchronic	repeated dose toxicity	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"}
UnifiedCodex:SCCS_SHADOW:beta.noael_studies	repeated dose toxicity	8	mg/kg bw/d	rat	oral	90-day	repeated dose toxicity	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"}
UnifiedCodex:SCCS_SHADOW:beta.noael_studies	repeated dose toxicity	5	mg/kg bw/day	rat	oral	90-day	repeated dose toxicity	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"}
UnifiedCodex:SCCS_SHADOW:beta.noael_studies	repeated dose toxicity	5	mg/kg bw/day	rat	oral	90-day	repeated dose toxicity	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"}
UnifiedCodex:SCCS_SHADOW:beta.noael_studies	repeated dose toxicity	8	mg/kg bw/d	rat	-	subchronic	repeated dose toxicity	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"}
UnifiedCodex:SCCS_SHADOW:beta.noael_studies	repeated dose toxicity	8	mg/kg bw/d	human	-	subchronic	repeated dose toxicity	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"}
UnifiedCodex:SCCS_SHADOW:beta.noael_studies	repeated dose toxicity	5	mg/kg bw/d	rat	oral	subchronic	repeated dose toxicity	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"}
UnifiedCodex:SCCS_SHADOW:beta.noael_studies	repeated dose toxicity	8	mg/kg bw/day	rat	oral	subchronic	repeated dose toxicity	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"}

openFDA substances 4 endpoints

Source	Endpoint Type	Value	Unit	Species	Route	Duration	Study Type	Reference
openFDA substances	FDA UNII substance identifier	U770QIT64J	UNII	-	-	-	chemical	{"approval_status":null,"molecular_formula":"C6H8N2","source_table":"substance_identifiers_fda","substance_class":"chemical","unii_code":"U770QIT64J"}
openFDA substances	FDA UNII substance identifier	U770QIT64J	UNII	-	-	-	chemical	{"approval_status":null,"molecular_formula":"C6H8N2","source_table":"substance_identifiers_fda","substance_class":"chemical","unii_code":"U770QIT64J"}
openFDA substances	FDA UNII substance identifier	U770QIT64J	UNII	-	-	-	chemical	{"approval_status":null,"molecular_formula":"C6H8N2","source_table":"substance_identifiers_fda","substance_class":"chemical","unii_code":"U770QIT64J"}
openFDA substances	FDA UNII substance identifier	U770QIT64J	UNII	-	-	-	chemical	{"approval_status":null,"molecular_formula":"C6H8N2","source_table":"substance_identifiers_fda","substance_class":"chemical","unii_code":"U770QIT64J"}