NOAEL Studies Cosmetic Ingredient

N,N'-BIS(2-HYDROXYETHYL)-2-NITRO-P-PHENYLENEDIAMINE NOAEL Studies

CAS: 84041-77-0

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 1 endpoint

Source	Endpoint Type	Value	Unit	Species	Route	Duration	Study Type	Reference
COSMOS_DB	LOAEL	80	mg/kg bw/day	rat	oral	90 day	Subchronic	SCCS; Rossiello, E. and Andreini, I. (2005) B 034 – 13 week oral toxicity study in rats followed by a 4 week recovery period

SCCNFP_vision_codex 16 endpoints

Source	Endpoint Type	Value	Unit	Species	Route	Duration	Study Type	Reference
SCCNFP_vision_codex	NOAEL	=50	mg/kg bw/day	-	dermal	Sub-chronic	repeated dose toxicity	{"citation":"Ref.: 6 2","dose":"at week 6 in the middle and the high dose group and at week 13 in the high dose group only, calcium levels were increased in males and females at week 6 in the middle and the high dose group.","effect":"at week 6 in the middle and the high dose group and at week 13 in the high dose group only, calcium levels were increased in males and females at week 6 in the middle and the high dose group. Liver and kidney weights of males were increased in the high dose group. With the exception of inflammatory changes found in several organs in treated and control groups no relevant morphological changes were revealed. After the recovery period no differences in haematology, clinical chemistry and organ weights were seen. The NOAEL is 50 mg/kg bw/day, the NOEL 5 mg/kg bw/day. Ref.: 6 2.3.8. Sub-chronic dermal toxicity No data 2.3.9. Sub-chronic inhalation toxicity No data","page":6,"pdf":"out257_en.pdf","row_type":"noael_study","study_id":"out257_en_noael_001"}
SCCNFP_vision_codex	NOAEL	=5	mg/kg bw/day	-	dermal	Sub-chronic	repeated dose toxicity	{"citation":"Ref.: 6 2","dose":"e high dose group and at week 13 in the high dose group only, calcium levels were increased in males and females at week 6 in the middle and the high dose group.","effect":"e high dose group and at week 13 in the high dose group only, calcium levels were increased in males and females at week 6 in the middle and the high dose group. Liver and kidney weights of males were increased in the high dose group. With the exception of inflammatory changes found in several organs in treated and control groups no relevant morphological changes were revealed. After the recovery period no differences in haematology, clinical chemistry and organ weights were seen. The NOAEL is 50 mg/kg bw/day, the NOEL 5 mg/kg bw/day. Ref.: 6 2.3.8. Sub-chronic dermal toxicity No data 2.3.9. Sub-chronic inhalation toxicity No data","page":6,"pdf":"out257_en.pdf","row_type":"noael_study","study_id":"out257_en_noael_002"}
SCCNFP_vision_codex	NOAEL	=100	mg/kg bw/day	rat	dermal	-	dermal absorption	{"citation":"Ref.: 21 2","dose":"In the high dose group maternal food consumption and body weight gain was significantly reduced while the slightly lower body weight gain compared to controls in the 100 mg/kg bw/day group was not statistically significant.","effect":"treated groups. In the high dose group maternal food consumption and body weight gain was significantly reduced while the slightly lower body weight gain compared to controls in the 100 mg/kg bw/day group was not statistically significant. Reproduction parameters remained unaffected in all dose groups. The incidence of external, visceral, major and minor skeletal abnormalities was not changed by substance treatment. N,N’-bis-(2- hydroxyethyl)-2-nitro-p-phenylenediamine elicited maternal toxicity at 1000 mg/kg, the NOAEL in this study is 100 mg/kg bw/day. The NOAEL of embryotoxicity and teratogenicity is 1000 mg/kg bw/day. Ref.: 21 2.7. Toxicokinetics (incl. Percutaneous Absorption) Percutaneous penetration / dermal absorption of a hair dye formulation in rats Guideline : / Animal strain : Sprague Dawley rats (Him:OFA) 5 males and 5 females in each of 2 experiments Method : 14C ring labelled N,N’-bis-(2-hydroxyethyl)-2-nitro-p-phenylenediamine in a hair dye formulation (without developer), radiochemical purity > 98","page":9,"pdf":"out257_en.pdf","row_type":"noael_study","study_id":"out257_en_noael_003"}
SCCNFP_vision_codex	NOAEL	=1000	mg/kg bw/day	rat	dermal	-	dermal absorption	{"citation":"Ref.: 21 2","dose":"al food consumption and body weight gain was significantly reduced while the slightly lower body weight gain compared to controls in the 100 mg/kg bw/day group was not statistically significant.","effect":"al food consumption and body weight gain was significantly reduced while the slightly lower body weight gain compared to controls in the 100 mg/kg bw/day group was not statistically significant. Reproduction parameters remained unaffected in all dose groups. The incidence of external, visceral, major and minor skeletal abnormalities was not changed by substance treatment. N,N’-bis-(2- hydroxyethyl)-2-nitro-p-phenylenediamine elicited maternal toxicity at 1000 mg/kg, the NOAEL in this study is 100 mg/kg bw/day. The NOAEL of embryotoxicity and teratogenicity is 1000 mg/kg bw/day. Ref.: 21 2.7. Toxicokinetics (incl. Percutaneous Absorption) Percutaneous penetration / dermal absorption of a hair dye formulation in rats Guideline : / Animal strain : Sprague Dawley rats (Him:OFA) 5 males and 5 females in each of 2 experiments Method : 14C ring labelled N,N’-bis-(2-hydroxyethyl)-2-nitro-p-phenylenediamine in a hair dye formulation (without developer), radiochemical purity > 98 %, applied to the back skin for 30 minutes a","page":9,"pdf":"out257_en.pdf","row_type":"noael_study","study_id":"out257_en_noael_004"}
SCCNFP_vision_codex	NOAEL	=50	mg/kg bw/day	-	dermal	Sub-chronic	repeated dose toxicity	{"citation":"Ref.: 6 2","dose":"at week 6 in the middle and the high dose group and at week 13 in the high dose group only, calcium levels were increased in males and females at week 6 in the middle and the high dose group.","effect":"at week 6 in the middle and the high dose group and at week 13 in the high dose group only, calcium levels were increased in males and females at week 6 in the middle and the high dose group. Liver and kidney weights of males were increased in the high dose group. With the exception of inflammatory changes found in several organs in treated and control groups no relevant morphological changes were revealed. After the recovery period no differences in haematology, clinical chemistry and organ weights were seen. The NOAEL is 50 mg/kg bw/day, the NOEL 5 mg/kg bw/day. Ref.: 6 2.3.8. Sub-chronic dermal toxicity No data 2.3.9. Sub-chronic inhalation toxicity No data","page":6,"pdf":"out257_en.pdf","row_type":"noael_study","study_id":"out257_en_noael_001"}
SCCNFP_vision_codex	NOAEL	=5	mg/kg bw/day	-	dermal	Sub-chronic	repeated dose toxicity	{"citation":"Ref.: 6 2","dose":"e high dose group and at week 13 in the high dose group only, calcium levels were increased in males and females at week 6 in the middle and the high dose group.","effect":"e high dose group and at week 13 in the high dose group only, calcium levels were increased in males and females at week 6 in the middle and the high dose group. Liver and kidney weights of males were increased in the high dose group. With the exception of inflammatory changes found in several organs in treated and control groups no relevant morphological changes were revealed. After the recovery period no differences in haematology, clinical chemistry and organ weights were seen. The NOAEL is 50 mg/kg bw/day, the NOEL 5 mg/kg bw/day. Ref.: 6 2.3.8. Sub-chronic dermal toxicity No data 2.3.9. Sub-chronic inhalation toxicity No data","page":6,"pdf":"out257_en.pdf","row_type":"noael_study","study_id":"out257_en_noael_002"}
SCCNFP_vision_codex	NOAEL	=100	mg/kg bw/day	rat	dermal	-	dermal absorption	{"citation":"Ref.: 21 2","dose":"In the high dose group maternal food consumption and body weight gain was significantly reduced while the slightly lower body weight gain compared to controls in the 100 mg/kg bw/day group was not statistically significant.","effect":"treated groups. In the high dose group maternal food consumption and body weight gain was significantly reduced while the slightly lower body weight gain compared to controls in the 100 mg/kg bw/day group was not statistically significant. Reproduction parameters remained unaffected in all dose groups. The incidence of external, visceral, major and minor skeletal abnormalities was not changed by substance treatment. N,N’-bis-(2- hydroxyethyl)-2-nitro-p-phenylenediamine elicited maternal toxicity at 1000 mg/kg, the NOAEL in this study is 100 mg/kg bw/day. The NOAEL of embryotoxicity and teratogenicity is 1000 mg/kg bw/day. Ref.: 21 2.7. Toxicokinetics (incl. Percutaneous Absorption) Percutaneous penetration / dermal absorption of a hair dye formulation in rats Guideline : / Animal strain : Sprague Dawley rats (Him:OFA) 5 males and 5 females in each of 2 experiments Method : 14C ring labelled N,N’-bis-(2-hydroxyethyl)-2-nitro-p-phenylenediamine in a hair dye formulation (without developer), radiochemical purity > 98","page":9,"pdf":"out257_en.pdf","row_type":"noael_study","study_id":"out257_en_noael_003"}
SCCNFP_vision_codex	NOAEL	=1000	mg/kg bw/day	rat	dermal	-	dermal absorption	{"citation":"Ref.: 21 2","dose":"al food consumption and body weight gain was significantly reduced while the slightly lower body weight gain compared to controls in the 100 mg/kg bw/day group was not statistically significant.","effect":"al food consumption and body weight gain was significantly reduced while the slightly lower body weight gain compared to controls in the 100 mg/kg bw/day group was not statistically significant. Reproduction parameters remained unaffected in all dose groups. The incidence of external, visceral, major and minor skeletal abnormalities was not changed by substance treatment. N,N’-bis-(2- hydroxyethyl)-2-nitro-p-phenylenediamine elicited maternal toxicity at 1000 mg/kg, the NOAEL in this study is 100 mg/kg bw/day. The NOAEL of embryotoxicity and teratogenicity is 1000 mg/kg bw/day. Ref.: 21 2.7. Toxicokinetics (incl. Percutaneous Absorption) Percutaneous penetration / dermal absorption of a hair dye formulation in rats Guideline : / Animal strain : Sprague Dawley rats (Him:OFA) 5 males and 5 females in each of 2 experiments Method : 14C ring labelled N,N’-bis-(2-hydroxyethyl)-2-nitro-p-phenylenediamine in a hair dye formulation (without developer), radiochemical purity > 98 %, applied to the back skin for 30 minutes a","page":9,"pdf":"out257_en.pdf","row_type":"noael_study","study_id":"out257_en_noael_004"}
SCCNFP_vision_codex	NOAEL	=50	mg/kg bw/day	-	dermal	Sub-chronic	repeated dose toxicity	{"citation":"Ref.: 6 2","dose":"at week 6 in the middle and the high dose group and at week 13 in the high dose group only, calcium levels were increased in males and females at week 6 in the middle and the high dose group.","effect":"at week 6 in the middle and the high dose group and at week 13 in the high dose group only, calcium levels were increased in males and females at week 6 in the middle and the high dose group. Liver and kidney weights of males were increased in the high dose group. With the exception of inflammatory changes found in several organs in treated and control groups no relevant morphological changes were revealed. After the recovery period no differences in haematology, clinical chemistry and organ weights were seen. The NOAEL is 50 mg/kg bw/day, the NOEL 5 mg/kg bw/day. Ref.: 6 2.3.8. Sub-chronic dermal toxicity No data 2.3.9. Sub-chronic inhalation toxicity No data","page":6,"pdf":"out257_en.pdf","row_type":"noael_study","study_id":"out257_en_noael_001"}
SCCNFP_vision_codex	NOAEL	=5	mg/kg bw/day	-	dermal	Sub-chronic	repeated dose toxicity	{"citation":"Ref.: 6 2","dose":"e high dose group and at week 13 in the high dose group only, calcium levels were increased in males and females at week 6 in the middle and the high dose group.","effect":"e high dose group and at week 13 in the high dose group only, calcium levels were increased in males and females at week 6 in the middle and the high dose group. Liver and kidney weights of males were increased in the high dose group. With the exception of inflammatory changes found in several organs in treated and control groups no relevant morphological changes were revealed. After the recovery period no differences in haematology, clinical chemistry and organ weights were seen. The NOAEL is 50 mg/kg bw/day, the NOEL 5 mg/kg bw/day. Ref.: 6 2.3.8. Sub-chronic dermal toxicity No data 2.3.9. Sub-chronic inhalation toxicity No data","page":6,"pdf":"out257_en.pdf","row_type":"noael_study","study_id":"out257_en_noael_002"}
SCCNFP_vision_codex	NOAEL	=100	mg/kg bw/day	rat	dermal	-	dermal absorption	{"citation":"Ref.: 21 2","dose":"In the high dose group maternal food consumption and body weight gain was significantly reduced while the slightly lower body weight gain compared to controls in the 100 mg/kg bw/day group was not statistically significant.","effect":"treated groups. In the high dose group maternal food consumption and body weight gain was significantly reduced while the slightly lower body weight gain compared to controls in the 100 mg/kg bw/day group was not statistically significant. Reproduction parameters remained unaffected in all dose groups. The incidence of external, visceral, major and minor skeletal abnormalities was not changed by substance treatment. N,N’-bis-(2- hydroxyethyl)-2-nitro-p-phenylenediamine elicited maternal toxicity at 1000 mg/kg, the NOAEL in this study is 100 mg/kg bw/day. The NOAEL of embryotoxicity and teratogenicity is 1000 mg/kg bw/day. Ref.: 21 2.7. Toxicokinetics (incl. Percutaneous Absorption) Percutaneous penetration / dermal absorption of a hair dye formulation in rats Guideline : / Animal strain : Sprague Dawley rats (Him:OFA) 5 males and 5 females in each of 2 experiments Method : 14C ring labelled N,N’-bis-(2-hydroxyethyl)-2-nitro-p-phenylenediamine in a hair dye formulation (without developer), radiochemical purity > 98","page":9,"pdf":"out257_en.pdf","row_type":"noael_study","study_id":"out257_en_noael_003"}
SCCNFP_vision_codex	NOAEL	=1000	mg/kg bw/day	rat	dermal	-	dermal absorption	{"citation":"Ref.: 21 2","dose":"al food consumption and body weight gain was significantly reduced while the slightly lower body weight gain compared to controls in the 100 mg/kg bw/day group was not statistically significant.","effect":"al food consumption and body weight gain was significantly reduced while the slightly lower body weight gain compared to controls in the 100 mg/kg bw/day group was not statistically significant. Reproduction parameters remained unaffected in all dose groups. The incidence of external, visceral, major and minor skeletal abnormalities was not changed by substance treatment. N,N’-bis-(2- hydroxyethyl)-2-nitro-p-phenylenediamine elicited maternal toxicity at 1000 mg/kg, the NOAEL in this study is 100 mg/kg bw/day. The NOAEL of embryotoxicity and teratogenicity is 1000 mg/kg bw/day. Ref.: 21 2.7. Toxicokinetics (incl. Percutaneous Absorption) Percutaneous penetration / dermal absorption of a hair dye formulation in rats Guideline : / Animal strain : Sprague Dawley rats (Him:OFA) 5 males and 5 females in each of 2 experiments Method : 14C ring labelled N,N’-bis-(2-hydroxyethyl)-2-nitro-p-phenylenediamine in a hair dye formulation (without developer), radiochemical purity > 98 %, applied to the back skin for 30 minutes a","page":9,"pdf":"out257_en.pdf","row_type":"noael_study","study_id":"out257_en_noael_004"}
SCCNFP_vision_codex	NOAEL	=50	mg/kg bw/day	-	dermal	Sub-chronic	repeated dose toxicity	{"citation":"Ref.: 6 2","dose":"at week 6 in the middle and the high dose group and at week 13 in the high dose group only, calcium levels were increased in males and females at week 6 in the middle and the high dose group.","effect":"at week 6 in the middle and the high dose group and at week 13 in the high dose group only, calcium levels were increased in males and females at week 6 in the middle and the high dose group. Liver and kidney weights of males were increased in the high dose group. With the exception of inflammatory changes found in several organs in treated and control groups no relevant morphological changes were revealed. After the recovery period no differences in haematology, clinical chemistry and organ weights were seen. The NOAEL is 50 mg/kg bw/day, the NOEL 5 mg/kg bw/day. Ref.: 6 2.3.8. Sub-chronic dermal toxicity No data 2.3.9. Sub-chronic inhalation toxicity No data","page":6,"pdf":"out257_en.pdf","row_type":"noael_study","study_id":"out257_en_noael_001"}
SCCNFP_vision_codex	NOAEL	=5	mg/kg bw/day	-	dermal	Sub-chronic	repeated dose toxicity	{"citation":"Ref.: 6 2","dose":"e high dose group and at week 13 in the high dose group only, calcium levels were increased in males and females at week 6 in the middle and the high dose group.","effect":"e high dose group and at week 13 in the high dose group only, calcium levels were increased in males and females at week 6 in the middle and the high dose group. Liver and kidney weights of males were increased in the high dose group. With the exception of inflammatory changes found in several organs in treated and control groups no relevant morphological changes were revealed. After the recovery period no differences in haematology, clinical chemistry and organ weights were seen. The NOAEL is 50 mg/kg bw/day, the NOEL 5 mg/kg bw/day. Ref.: 6 2.3.8. Sub-chronic dermal toxicity No data 2.3.9. Sub-chronic inhalation toxicity No data","page":6,"pdf":"out257_en.pdf","row_type":"noael_study","study_id":"out257_en_noael_002"}
SCCNFP_vision_codex	NOAEL	=100	mg/kg bw/day	rat	dermal	-	dermal absorption	{"citation":"Ref.: 21 2","dose":"In the high dose group maternal food consumption and body weight gain was significantly reduced while the slightly lower body weight gain compared to controls in the 100 mg/kg bw/day group was not statistically significant.","effect":"treated groups. In the high dose group maternal food consumption and body weight gain was significantly reduced while the slightly lower body weight gain compared to controls in the 100 mg/kg bw/day group was not statistically significant. Reproduction parameters remained unaffected in all dose groups. The incidence of external, visceral, major and minor skeletal abnormalities was not changed by substance treatment. N,N’-bis-(2- hydroxyethyl)-2-nitro-p-phenylenediamine elicited maternal toxicity at 1000 mg/kg, the NOAEL in this study is 100 mg/kg bw/day. The NOAEL of embryotoxicity and teratogenicity is 1000 mg/kg bw/day. Ref.: 21 2.7. Toxicokinetics (incl. Percutaneous Absorption) Percutaneous penetration / dermal absorption of a hair dye formulation in rats Guideline : / Animal strain : Sprague Dawley rats (Him:OFA) 5 males and 5 females in each of 2 experiments Method : 14C ring labelled N,N’-bis-(2-hydroxyethyl)-2-nitro-p-phenylenediamine in a hair dye formulation (without developer), radiochemical purity > 98","page":9,"pdf":"out257_en.pdf","row_type":"noael_study","study_id":"out257_en_noael_003"}
SCCNFP_vision_codex	NOAEL	=1000	mg/kg bw/day	rat	dermal	-	dermal absorption	{"citation":"Ref.: 21 2","dose":"al food consumption and body weight gain was significantly reduced while the slightly lower body weight gain compared to controls in the 100 mg/kg bw/day group was not statistically significant.","effect":"al food consumption and body weight gain was significantly reduced while the slightly lower body weight gain compared to controls in the 100 mg/kg bw/day group was not statistically significant. Reproduction parameters remained unaffected in all dose groups. The incidence of external, visceral, major and minor skeletal abnormalities was not changed by substance treatment. N,N’-bis-(2- hydroxyethyl)-2-nitro-p-phenylenediamine elicited maternal toxicity at 1000 mg/kg, the NOAEL in this study is 100 mg/kg bw/day. The NOAEL of embryotoxicity and teratogenicity is 1000 mg/kg bw/day. Ref.: 21 2.7. Toxicokinetics (incl. Percutaneous Absorption) Percutaneous penetration / dermal absorption of a hair dye formulation in rats Guideline : / Animal strain : Sprague Dawley rats (Him:OFA) 5 males and 5 females in each of 2 experiments Method : 14C ring labelled N,N’-bis-(2-hydroxyethyl)-2-nitro-p-phenylenediamine in a hair dye formulation (without developer), radiochemical purity > 98 %, applied to the back skin for 30 minutes a","page":9,"pdf":"out257_en.pdf","row_type":"noael_study","study_id":"out257_en_noael_004"}

SCCS_vision_codex 44 endpoints

Source	Endpoint Type	Value	Unit	Species	Route	Duration	Study Type	Reference
SCCS_vision_codex	NOAEL	=240	mg/kg/day	-	-	Chronic	genotoxicity	{"citation":"Ref.: 11 3","dose":"SCCS/1228/09, revision of 12.07.10 Opinion on N,N'-bis-(2-Hydroxyethyl)-2-nitro-p-phenylenediamine __________________________________________________________________________________ 16 Conclusion On the basis of these results, the mid-dose (240 mg/kg/day) may be considered the No Observed Adverse Effect Level (NOAEL) for N,N’-bis-(2-hydroxyethyl...","effect":"SCCS/1228/09, revision of 12.07.10 Opinion on N,N'-bis-(2-Hydroxyethyl)-2-nitro-p-phenylenediamine __________________________________________________________________________________ 16 Conclusion On the basis of these results, the mid-dose (240 mg/kg/day) may be considered the No Observed Adverse Effect Level (NOAEL) for N,N’-bis-(2-hydroxyethyl)-2-nitro-p- phenylenediamine. Ref.: 11 3.3.5.3. Chronic (> 12 months) toxicity No data submitted 3.3.6. Mutagenicity / Genotoxicity 3.3.6.1 Mutagenicity / Genotoxicity in vitro Taken from SCCNFP/0781/04 Reverse Mutation Testing Using Bacteria Guideline: OECD 471 (1983) Species/Strain: Salmonella typhimurium (TA98, TA98 NR) Test item: HC Violet B5 Batch: / Purity: / Replicate: 2 experiments Doses: 100, 500, 1000, 2500, 5000, 7500, 10000 μg/plate Metabolic Act.: Phenobarbi","page":16,"pdf":"sccs_o_019.pdf","row_type":"noael_study","study_id":"sccs_o_019_noael_001"}
SCCS_vision_codex	NOAEL	=1200	mg/kg/day	human	-	-	NOAEL study	{"citation":"Ref.: 12 3","dose":"cantly increase in the percentage of male foetuses noted in the low dose group was not considered to be of toxicological significance.","effect":"cantly increase in the percentage of male foetuses noted in the low dose group was not considered to be of toxicological significance. The number of small foetuses was comparable between groups. No relevance was attributed to the minor anomalies noted in one low dose foetus. Visceral examination did not show any dose related findings. No relevant foetal treatment- related skeletal changes were reported. Conclusion No maternal toxicity, foetal toxicity or teratogenicity was seen. On the basis of these results, the No Observed Adverse Effect Level (NOAEL) for N,N’-bis-(2-hydroxyethyl)-2- nitro-p-phenylenediamine should be considered to be 1200 mg/kg/day. Ref.: 12 3.3.9. Toxicokinetics No data submitted 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 3.3.13. Safety evaluation (including calculation of the MoS) CAL","page":27,"pdf":"sccs_o_019.pdf","row_type":"noael_study","study_id":"sccs_o_019_noael_002"}
SCCS_vision_codex	NOAEL	=50	mg/kg bw/day	rat	-	4 weeks	NOAEL study	{"citation":"Ref.: 6 Comment The dose-spacing between the mid and high dose was very large","dose":"at week 6 in the middle and the high dose group and at week 13 in the high dose group only, calcium levels were increased in males and females at week 6 in the middle and the high dose group.","effect":"at week 6 in the middle and the high dose group and at week 13 in the high dose group only, calcium levels were increased in males and females at week 6 in the middle and the high dose group. Liver and kidney weights of males were increased in the high dose group. With the exception of inflammatory changes found in several organs in treated and control groups no relevant morphological changes were revealed. After the recovery period no differences in haematology, clinical chemistry and organ weights were seen. The NOAEL is 50 mg/kg bw/day, the NOEL 5 mg/kg bw/day. Ref.: 6 Comment The dose-spacing between the mid and high dose was very large. Guideline: OECD 408 (1998) Species/strain: rat, Wistar Hannover (HsdBrlHan:Wist) Group size: 120 (10 males and 10 females per group; control and high dose group: additional 5 males and 5 females for 4 weeks of recovery) Test substance: B034 Batch: DALA 013106 (SAT 040411) Purity: 99.5%","page":15,"pdf":"sccs_o_096.pdf","row_type":"noael_study","study_id":"sccs_o_096_noael_001"}
SCCS_vision_codex	NOAEL	=5	mg/kg bw/day	rat	-	4 weeks	NOAEL study	{"citation":"Ref.: 6 Comment The dose-spacing between the mid and high dose was very large","dose":"e high dose group and at week 13 in the high dose group only, calcium levels were increased in males and females at week 6 in the middle and the high dose group.","effect":"e high dose group and at week 13 in the high dose group only, calcium levels were increased in males and females at week 6 in the middle and the high dose group. Liver and kidney weights of males were increased in the high dose group. With the exception of inflammatory changes found in several organs in treated and control groups no relevant morphological changes were revealed. After the recovery period no differences in haematology, clinical chemistry and organ weights were seen. The NOAEL is 50 mg/kg bw/day, the NOEL 5 mg/kg bw/day. Ref.: 6 Comment The dose-spacing between the mid and high dose was very large. Guideline: OECD 408 (1998) Species/strain: rat, Wistar Hannover (HsdBrlHan:Wist) Group size: 120 (10 males and 10 females per group; control and high dose group: additional 5 males and 5 females for 4 weeks of recovery) Test substance: B034 Batch: DALA 013106 (SAT 040411) Purity: 99.5%","page":15,"pdf":"sccs_o_096.pdf","row_type":"noael_study","study_id":"sccs_o_096_noael_002"}
SCCS_vision_codex	NOAEL	=1000	mg/kg	rat	oral	Prenatal	developmental toxicity	{"citation":"Ref.: 21 Prenatal developmental study Guideline: OECD 414 (2001) Species/strain: rat, Wistar Hannover (HsdBrlHan:Wist) Group size: 100 (25 females per dose group) Test substance: B034 Ba","dose":"SCCS/1463/12 Opinion on N,N'-bis-(2-Hydroxyethyl)-2-nitro-p-phenylenediamine ___________________________________________________________________________________________ 32 unaffected in all dose groups.","effect":"SCCS/1463/12 Opinion on N,N'-bis-(2-Hydroxyethyl)-2-nitro-p-phenylenediamine ___________________________________________________________________________________________ 32 unaffected in all dose groups. The incidence of external, visceral, major and minor skeletal abnormalities was not changed by substance treatment. N,N’-bis-(2- hydroxyethyl)-2-nitro- p-phenylenediamine elicited maternal toxicity at 1000 mg/kg, the NOAEL in this study is 100 mg/kg bw/day. The NOAEL of embryotoxicity and teratogenicity is 1000 mg/kg bw/day. Ref.: 21 Prenatal developmental study Guideline: OECD 414 (2001) Species/strain: rat, Wistar Hannover (HsdBrlHan:Wist) Group size: 100 (25 females per dose group) Test substance: B034 Batch: DALA 013106 (SAT 040411) Purity: 99.5% Vehicle: 0.5% aqueous carboxymethylcellulose Dose levels: 0, 300, 600 and 1200 mg/kg bw Dose volume: 10 ml/kg bw Route: oral gavage Administration: once daily from gestation day (GD)","page":32,"pdf":"sccs_o_096.pdf","row_type":"noael_study","study_id":"sccs_o_096_noael_006"}
SCCS_vision_codex	NOAEL	=100	mg/kg bw/day	rat	oral	Prenatal	developmental toxicity	{"citation":"Ref.: 21 Prenatal developmental study Guideline: OECD 414 (2001) Species/strain: rat, Wistar Hannover (HsdBrlHan:Wist) Group size: 100 (25 females per dose group) Test substance: B034 Ba","dose":"SCCS/1463/12 Opinion on N,N'-bis-(2-Hydroxyethyl)-2-nitro-p-phenylenediamine ___________________________________________________________________________________________ 32 unaffected in all dose groups.","effect":"SCCS/1463/12 Opinion on N,N'-bis-(2-Hydroxyethyl)-2-nitro-p-phenylenediamine ___________________________________________________________________________________________ 32 unaffected in all dose groups. The incidence of external, visceral, major and minor skeletal abnormalities was not changed by substance treatment. N,N’-bis-(2- hydroxyethyl)-2-nitro- p-phenylenediamine elicited maternal toxicity at 1000 mg/kg, the NOAEL in this study is 100 mg/kg bw/day. The NOAEL of embryotoxicity and teratogenicity is 1000 mg/kg bw/day. Ref.: 21 Prenatal developmental study Guideline: OECD 414 (2001) Species/strain: rat, Wistar Hannover (HsdBrlHan:Wist) Group size: 100 (25 females per dose group) Test substance: B034 Batch: DALA 013106 (SAT 040411) Purity: 99.5% Vehicle: 0.5% aqueous carboxymethylcellulose Dose levels: 0, 300, 600 and 1200 mg/kg bw Dose volume: 10 ml/kg bw Route: oral gavage Administration: once daily from gestation day (GD) 5 through day 19 GLP statement: in complianc","page":32,"pdf":"sccs_o_096.pdf","row_type":"noael_study","study_id":"sccs_o_096_noael_007"}
SCCS_vision_codex	NOAEL	=720	mg/kg bw/day	mouse	-	90 day	irritation	{"dose":"The No Observed Adverse Effect Level (NOAEL) for N,N’-bis-(2-hydroxyethyl)-2-nitro-p- phenylenediamine in the 90 day study was considered to be 240 mg/kg bw/day, based on effects on kidney and urea at 720 mg/kg bw/day, which seemed to be the target organ.","effect":"________________________________________________ 35 Toxicity No mortalities occurred up to 5 g/kg bw, so N,N’-bis-(2-hydroxyethyl)-2-nitro-p- phenylenediamine showed no acute toxicity. The No Observed Adverse Effect Level (NOAEL) for N,N’-bis-(2-hydroxyethyl)-2-nitro-p- phenylenediamine in the 90 day study was considered to be 240 mg/kg bw/day, based on effects on kidney and urea at 720 mg/kg bw/day, which seemed to be the target organ. Since no maternal toxicity, foetal toxicity or teratogenicity was seen, the No Observed Adverse Effect Level (NOAEL) for N,N’-bis-(2-hydroxyethyl)-2-nitro-p-phenylenediamine for these endpoints was considered to be 1200 mg/kg/day. Skin/eye irritation and sensitisation Neat N,N’-bis-(2-hydroxyethyl)-2-nitro-p-phenylenediamine was not irritant when applied to rabbit skin. However, it was noted that 10% N,N’-bis-(2-hydroxyethyl)-2-nitro-p- phenylenediamine in acetone:olive oil was slightly irritant to the mouse ear in the LLNA test. It was irritant to rabbit eyes. N,N’-bis-(2-hydroxyethyl)-2-nitro-p-phenylenediamine was n","page":35,"pdf":"sccs_o_096.pdf","row_type":"noael_study","study_id":"sccs_o_096_noael_011"}
SCCS_vision_codex	NOAEL	=0.017	mg/kg bw/d	rat	oral	90-day	dermal absorption	{"dose":"___________________________________________________________________________ 36 No data submitted 3.3.12 Special investigations 3.3.13 Safety evaluation (including calculation of the MoS) CALCULATION OF THE MARGIN OF SAFETY (Oxidative conditions) (on head concentration 1%) Absorption through the skin A = 1.76 µg/cm² Skin Area surface SAS = 580 cm...","effect":"___________________________________________________________________________ 36 No data submitted 3.3.12 Special investigations 3.3.13 Safety evaluation (including calculation of the MoS) CALCULATION OF THE MARGIN OF SAFETY (Oxidative conditions) (on head concentration 1%) Absorption through the skin A = 1.76 µg/cm² Skin Area surface SAS = 580 cm2 Dermal absorption per treatment SAS x A x 0.001 = 1.021 mg Typical body weight of human = 60 kg Systemic exposure dose (SED) SAS x A x 0.001/60 = 0.017 mg/kg bw/d No observed adverse effect level NOAEL = 240 mg/kg bw/d (90-day, oral, rat) Bioavailability 50%* = 120 mg/kg bw/d Margin of Safety adjusted NOAEL/SED = 7100 * standard procedure according to the SCCS's Notes of Guidance for the testing of cosmetic ingredients and their safety evaluation. (Non-oxidative conditions) (on head concentration 1.5%) Absorption through the skin A = 2.97 µg/cm² Skin Area surface SAS = 580 cm2 Dermal absorption per treatment SAS x A x 0.001 = 1.723 mg Typical body weight of human = 60 kg Systemic exposure dose (SED)","page":36,"pdf":"sccs_o_196.pdf","row_type":"noael_study","study_id":"sccs_o_196_noael_010"}
SCCS_vision_codex	NOAEL	=240	mg/kg bw/d	rat	oral	90-day	dermal absorption	{"dose":"__________________________________________ 36 No data submitted 3.3.12 Special investigations 3.3.13 Safety evaluation (including calculation of the MoS) CALCULATION OF THE MARGIN OF SAFETY (Oxidative conditions) (on head concentration 1%) Absorption through the skin A = 1.76 µg/cm² Skin Area surface SAS = 580 cm2 Dermal absorption per treatment...","effect":"__________________________________________ 36 No data submitted 3.3.12 Special investigations 3.3.13 Safety evaluation (including calculation of the MoS) CALCULATION OF THE MARGIN OF SAFETY (Oxidative conditions) (on head concentration 1%) Absorption through the skin A = 1.76 µg/cm² Skin Area surface SAS = 580 cm2 Dermal absorption per treatment SAS x A x 0.001 = 1.021 mg Typical body weight of human = 60 kg Systemic exposure dose (SED) SAS x A x 0.001/60 = 0.017 mg/kg bw/d No observed adverse effect level NOAEL = 240 mg/kg bw/d (90-day, oral, rat) Bioavailability 50%* = 120 mg/kg bw/d Margin of Safety adjusted NOAEL/SED = 7100 * standard procedure according to the SCCS's Notes of Guidance for the testing of cosmetic ingredients and their safety evaluation. (Non-oxidative conditions) (on head concentration 1.5%) Absorption through the skin A = 2.97 µg/cm² Skin Area surface SAS = 580 cm2 Dermal absorption per treatment SAS x A x 0.001 = 1.723 mg Typical body weight of human = 60 kg Systemic exposure dose (SED) SAS x","page":36,"pdf":"sccs_o_196.pdf","row_type":"noael_study","study_id":"sccs_o_196_noael_011"}
SCCS_vision_codex	NOAEL	=120	mg/kg bw/d	rat	oral	90-day	dermal absorption	{"dose":"ty evaluation (including calculation of the MoS) CALCULATION OF THE MARGIN OF SAFETY (Oxidative conditions) (on head concentration 1%) Absorption through the skin A = 1.76 µg/cm² Skin Area surface SAS = 580 cm2 Dermal absorption per treatment SAS x A x 0.001 = 1.021 mg Typical body weight of human = 60 kg Systemic exposure dose (SED) SAS x A x 0...","effect":"ty evaluation (including calculation of the MoS) CALCULATION OF THE MARGIN OF SAFETY (Oxidative conditions) (on head concentration 1%) Absorption through the skin A = 1.76 µg/cm² Skin Area surface SAS = 580 cm2 Dermal absorption per treatment SAS x A x 0.001 = 1.021 mg Typical body weight of human = 60 kg Systemic exposure dose (SED) SAS x A x 0.001/60 = 0.017 mg/kg bw/d No observed adverse effect level NOAEL = 240 mg/kg bw/d (90-day, oral, rat) Bioavailability 50%* = 120 mg/kg bw/d Margin of Safety adjusted NOAEL/SED = 7100 * standard procedure according to the SCCS's Notes of Guidance for the testing of cosmetic ingredients and their safety evaluation. (Non-oxidative conditions) (on head concentration 1.5%) Absorption through the skin A = 2.97 µg/cm² Skin Area surface SAS = 580 cm2 Dermal absorption per treatment SAS x A x 0.001 = 1.723 mg Typical body weight of human = 60 kg Systemic exposure dose (SED) SAS x A x 0.001/60 = 0.029 mg/kg bw/d No observed adverse effect level NOAEL = 240 mg/kg bw/d (90-day, oral, rat)","page":36,"pdf":"sccs_o_196.pdf","row_type":"noael_study","study_id":"sccs_o_196_noael_012"}
SCCS_vision_codex	NOAEL	=0.029	mg/kg bw/d	rat	oral	90-day	dermal absorption	{"dose":"rat) Bioavailability 50%* = 120 mg/kg bw/d Margin of Safety adjusted NOAEL/SED = 7100 * standard procedure according to the SCCS's Notes of Guidance for the testing of cosmetic ingredients and their safety evaluation.","effect":"rat) Bioavailability 50%* = 120 mg/kg bw/d Margin of Safety adjusted NOAEL/SED = 7100 * standard procedure according to the SCCS's Notes of Guidance for the testing of cosmetic ingredients and their safety evaluation. (Non-oxidative conditions) (on head concentration 1.5%) Absorption through the skin A = 2.97 µg/cm² Skin Area surface SAS = 580 cm2 Dermal absorption per treatment SAS x A x 0.001 = 1.723 mg Typical body weight of human = 60 kg Systemic exposure dose (SED) SAS x A x 0.001/60 = 0.029 mg/kg bw/d No observed adverse effect level NOAEL = 240 mg/kg bw/d (90-day, oral, rat) Bioavailability 50%* = 120 mg/kg bw/d Margin of Safety adjusted NOAEL/SED = 4100 * standard procedure according to the SCCS's Notes of Guidance for the testing of cosmetic ingredients and their safety evaluation. 3.3.14 Discussion Physico-chemical properties N,N’-bis-(2-hydroxyethyl)-2-nitro-p-phenylenediamine is used as a direct hair dye for hair colouring products. It is also used in oxidative hair dye formulations with and without an oxidising agent (e.g. hydrog","page":36,"pdf":"sccs_o_196.pdf","row_type":"noael_study","study_id":"sccs_o_196_noael_013"}
SCCS_vision_codex	NOAEL	=240	mg/kg/day	-	-	Chronic	genotoxicity	{"citation":"Ref.: 11 3","dose":"SCCS/1228/09, revision of 12.07.10 Opinion on N,N'-bis-(2-Hydroxyethyl)-2-nitro-p-phenylenediamine __________________________________________________________________________________ 16 Conclusion On the basis of these results, the mid-dose (240 mg/kg/day) may be considered the No Observed Adverse Effect Level (NOAEL) for N,N’-bis-(2-hydroxyethyl...","effect":"SCCS/1228/09, revision of 12.07.10 Opinion on N,N'-bis-(2-Hydroxyethyl)-2-nitro-p-phenylenediamine __________________________________________________________________________________ 16 Conclusion On the basis of these results, the mid-dose (240 mg/kg/day) may be considered the No Observed Adverse Effect Level (NOAEL) for N,N’-bis-(2-hydroxyethyl)-2-nitro-p- phenylenediamine. Ref.: 11 3.3.5.3. Chronic (> 12 months) toxicity No data submitted 3.3.6. Mutagenicity / Genotoxicity 3.3.6.1 Mutagenicity / Genotoxicity in vitro Taken from SCCNFP/0781/04 Reverse Mutation Testing Using Bacteria Guideline: OECD 471 (1983) Species/Strain: Salmonella typhimurium (TA98, TA98 NR) Test item: HC Violet B5 Batch: / Purity: / Replicate: 2 experiments Doses: 100, 500, 1000, 2500, 5000, 7500, 10000 μg/plate Metabolic Act.: Phenobarbi","page":16,"pdf":"sccs_o_019.pdf","row_type":"noael_study","study_id":"sccs_o_019_noael_001"}
SCCS_vision_codex	NOAEL	=1200	mg/kg/day	human	-	-	NOAEL study	{"citation":"Ref.: 12 3","dose":"cantly increase in the percentage of male foetuses noted in the low dose group was not considered to be of toxicological significance.","effect":"cantly increase in the percentage of male foetuses noted in the low dose group was not considered to be of toxicological significance. The number of small foetuses was comparable between groups. No relevance was attributed to the minor anomalies noted in one low dose foetus. Visceral examination did not show any dose related findings. No relevant foetal treatment- related skeletal changes were reported. Conclusion No maternal toxicity, foetal toxicity or teratogenicity was seen. On the basis of these results, the No Observed Adverse Effect Level (NOAEL) for N,N’-bis-(2-hydroxyethyl)-2- nitro-p-phenylenediamine should be considered to be 1200 mg/kg/day. Ref.: 12 3.3.9. Toxicokinetics No data submitted 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 3.3.13. Safety evaluation (including calculation of the MoS) CAL","page":27,"pdf":"sccs_o_019.pdf","row_type":"noael_study","study_id":"sccs_o_019_noael_002"}
SCCS_vision_codex	NOAEL	=240	mg/kg/day	-	-	Chronic	genotoxicity	{"citation":"Ref.: 11 3","dose":"SCCS/1228/09, revision of 12.07.10 Opinion on N,N'-bis-(2-Hydroxyethyl)-2-nitro-p-phenylenediamine __________________________________________________________________________________ 16 Conclusion On the basis of these results, the mid-dose (240 mg/kg/day) may be considered the No Observed Adverse Effect Level (NOAEL) for N,N’-bis-(2-hydroxyethyl...","effect":"SCCS/1228/09, revision of 12.07.10 Opinion on N,N'-bis-(2-Hydroxyethyl)-2-nitro-p-phenylenediamine __________________________________________________________________________________ 16 Conclusion On the basis of these results, the mid-dose (240 mg/kg/day) may be considered the No Observed Adverse Effect Level (NOAEL) for N,N’-bis-(2-hydroxyethyl)-2-nitro-p- phenylenediamine. Ref.: 11 3.3.5.3. Chronic (> 12 months) toxicity No data submitted 3.3.6. Mutagenicity / Genotoxicity 3.3.6.1 Mutagenicity / Genotoxicity in vitro Taken from SCCNFP/0781/04 Reverse Mutation Testing Using Bacteria Guideline: OECD 471 (1983) Species/Strain: Salmonella typhimurium (TA98, TA98 NR) Test item: HC Violet B5 Batch: / Purity: / Replicate: 2 experiments Doses: 100, 500, 1000, 2500, 5000, 7500, 10000 μg/plate Metabolic Act.: Phenobarbi","page":16,"pdf":"sccs_o_019.pdf","row_type":"noael_study","study_id":"sccs_o_019_noael_001"}
SCCS_vision_codex	NOAEL	=1200	mg/kg/day	human	-	-	NOAEL study	{"citation":"Ref.: 12 3","dose":"cantly increase in the percentage of male foetuses noted in the low dose group was not considered to be of toxicological significance.","effect":"cantly increase in the percentage of male foetuses noted in the low dose group was not considered to be of toxicological significance. The number of small foetuses was comparable between groups. No relevance was attributed to the minor anomalies noted in one low dose foetus. Visceral examination did not show any dose related findings. No relevant foetal treatment- related skeletal changes were reported. Conclusion No maternal toxicity, foetal toxicity or teratogenicity was seen. On the basis of these results, the No Observed Adverse Effect Level (NOAEL) for N,N’-bis-(2-hydroxyethyl)-2- nitro-p-phenylenediamine should be considered to be 1200 mg/kg/day. Ref.: 12 3.3.9. Toxicokinetics No data submitted 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 3.3.13. Safety evaluation (including calculation of the MoS) CAL","page":27,"pdf":"sccs_o_019.pdf","row_type":"noael_study","study_id":"sccs_o_019_noael_002"}
SCCS_vision_codex	NOAEL	=50	mg/kg bw/day	rat	-	4 weeks	NOAEL study	{"citation":"Ref.: 6 Comment The dose-spacing between the mid and high dose was very large","dose":"at week 6 in the middle and the high dose group and at week 13 in the high dose group only, calcium levels were increased in males and females at week 6 in the middle and the high dose group.","effect":"at week 6 in the middle and the high dose group and at week 13 in the high dose group only, calcium levels were increased in males and females at week 6 in the middle and the high dose group. Liver and kidney weights of males were increased in the high dose group. With the exception of inflammatory changes found in several organs in treated and control groups no relevant morphological changes were revealed. After the recovery period no differences in haematology, clinical chemistry and organ weights were seen. The NOAEL is 50 mg/kg bw/day, the NOEL 5 mg/kg bw/day. Ref.: 6 Comment The dose-spacing between the mid and high dose was very large. Guideline: OECD 408 (1998) Species/strain: rat, Wistar Hannover (HsdBrlHan:Wist) Group size: 120 (10 males and 10 females per group; control and high dose group: additional 5 males and 5 females for 4 weeks of recovery) Test substance: B034 Batch: DALA 013106 (SAT 040411) Purity: 99.5%","page":15,"pdf":"sccs_o_096.pdf","row_type":"noael_study","study_id":"sccs_o_096_noael_001"}
SCCS_vision_codex	NOAEL	=5	mg/kg bw/day	rat	-	4 weeks	NOAEL study	{"citation":"Ref.: 6 Comment The dose-spacing between the mid and high dose was very large","dose":"e high dose group and at week 13 in the high dose group only, calcium levels were increased in males and females at week 6 in the middle and the high dose group.","effect":"e high dose group and at week 13 in the high dose group only, calcium levels were increased in males and females at week 6 in the middle and the high dose group. Liver and kidney weights of males were increased in the high dose group. With the exception of inflammatory changes found in several organs in treated and control groups no relevant morphological changes were revealed. After the recovery period no differences in haematology, clinical chemistry and organ weights were seen. The NOAEL is 50 mg/kg bw/day, the NOEL 5 mg/kg bw/day. Ref.: 6 Comment The dose-spacing between the mid and high dose was very large. Guideline: OECD 408 (1998) Species/strain: rat, Wistar Hannover (HsdBrlHan:Wist) Group size: 120 (10 males and 10 females per group; control and high dose group: additional 5 males and 5 females for 4 weeks of recovery) Test substance: B034 Batch: DALA 013106 (SAT 040411) Purity: 99.5%","page":15,"pdf":"sccs_o_096.pdf","row_type":"noael_study","study_id":"sccs_o_096_noael_002"}
SCCS_vision_codex	NOAEL	=1000	mg/kg	rat	oral	Prenatal	developmental toxicity	{"citation":"Ref.: 21 Prenatal developmental study Guideline: OECD 414 (2001) Species/strain: rat, Wistar Hannover (HsdBrlHan:Wist) Group size: 100 (25 females per dose group) Test substance: B034 Ba","dose":"SCCS/1463/12 Opinion on N,N'-bis-(2-Hydroxyethyl)-2-nitro-p-phenylenediamine ___________________________________________________________________________________________ 32 unaffected in all dose groups.","effect":"SCCS/1463/12 Opinion on N,N'-bis-(2-Hydroxyethyl)-2-nitro-p-phenylenediamine ___________________________________________________________________________________________ 32 unaffected in all dose groups. The incidence of external, visceral, major and minor skeletal abnormalities was not changed by substance treatment. N,N’-bis-(2- hydroxyethyl)-2-nitro- p-phenylenediamine elicited maternal toxicity at 1000 mg/kg, the NOAEL in this study is 100 mg/kg bw/day. The NOAEL of embryotoxicity and teratogenicity is 1000 mg/kg bw/day. Ref.: 21 Prenatal developmental study Guideline: OECD 414 (2001) Species/strain: rat, Wistar Hannover (HsdBrlHan:Wist) Group size: 100 (25 females per dose group) Test substance: B034 Batch: DALA 013106 (SAT 040411) Purity: 99.5% Vehicle: 0.5% aqueous carboxymethylcellulose Dose levels: 0, 300, 600 and 1200 mg/kg bw Dose volume: 10 ml/kg bw Route: oral gavage Administration: once daily from gestation day (GD)","page":32,"pdf":"sccs_o_096.pdf","row_type":"noael_study","study_id":"sccs_o_096_noael_006"}
SCCS_vision_codex	NOAEL	=100	mg/kg bw/day	rat	oral	Prenatal	developmental toxicity	{"citation":"Ref.: 21 Prenatal developmental study Guideline: OECD 414 (2001) Species/strain: rat, Wistar Hannover (HsdBrlHan:Wist) Group size: 100 (25 females per dose group) Test substance: B034 Ba","dose":"SCCS/1463/12 Opinion on N,N'-bis-(2-Hydroxyethyl)-2-nitro-p-phenylenediamine ___________________________________________________________________________________________ 32 unaffected in all dose groups.","effect":"SCCS/1463/12 Opinion on N,N'-bis-(2-Hydroxyethyl)-2-nitro-p-phenylenediamine ___________________________________________________________________________________________ 32 unaffected in all dose groups. The incidence of external, visceral, major and minor skeletal abnormalities was not changed by substance treatment. N,N’-bis-(2- hydroxyethyl)-2-nitro- p-phenylenediamine elicited maternal toxicity at 1000 mg/kg, the NOAEL in this study is 100 mg/kg bw/day. The NOAEL of embryotoxicity and teratogenicity is 1000 mg/kg bw/day. Ref.: 21 Prenatal developmental study Guideline: OECD 414 (2001) Species/strain: rat, Wistar Hannover (HsdBrlHan:Wist) Group size: 100 (25 females per dose group) Test substance: B034 Batch: DALA 013106 (SAT 040411) Purity: 99.5% Vehicle: 0.5% aqueous carboxymethylcellulose Dose levels: 0, 300, 600 and 1200 mg/kg bw Dose volume: 10 ml/kg bw Route: oral gavage Administration: once daily from gestation day (GD) 5 through day 19 GLP statement: in complianc","page":32,"pdf":"sccs_o_096.pdf","row_type":"noael_study","study_id":"sccs_o_096_noael_007"}
SCCS_vision_codex	NOAEL	=720	mg/kg bw/day	mouse	-	90 day	irritation	{"dose":"The No Observed Adverse Effect Level (NOAEL) for N,N’-bis-(2-hydroxyethyl)-2-nitro-p- phenylenediamine in the 90 day study was considered to be 240 mg/kg bw/day, based on effects on kidney and urea at 720 mg/kg bw/day, which seemed to be the target organ.","effect":"________________________________________________ 35 Toxicity No mortalities occurred up to 5 g/kg bw, so N,N’-bis-(2-hydroxyethyl)-2-nitro-p- phenylenediamine showed no acute toxicity. The No Observed Adverse Effect Level (NOAEL) for N,N’-bis-(2-hydroxyethyl)-2-nitro-p- phenylenediamine in the 90 day study was considered to be 240 mg/kg bw/day, based on effects on kidney and urea at 720 mg/kg bw/day, which seemed to be the target organ. Since no maternal toxicity, foetal toxicity or teratogenicity was seen, the No Observed Adverse Effect Level (NOAEL) for N,N’-bis-(2-hydroxyethyl)-2-nitro-p-phenylenediamine for these endpoints was considered to be 1200 mg/kg/day. Skin/eye irritation and sensitisation Neat N,N’-bis-(2-hydroxyethyl)-2-nitro-p-phenylenediamine was not irritant when applied to rabbit skin. However, it was noted that 10% N,N’-bis-(2-hydroxyethyl)-2-nitro-p- phenylenediamine in acetone:olive oil was slightly irritant to the mouse ear in the LLNA test. It was irritant to rabbit eyes. N,N’-bis-(2-hydroxyethyl)-2-nitro-p-phenylenediamine was n","page":35,"pdf":"sccs_o_096.pdf","row_type":"noael_study","study_id":"sccs_o_096_noael_011"}
SCCS_vision_codex	NOAEL	=50	mg/kg bw/day	rat	-	4 weeks	NOAEL study	{"citation":"Ref.: 6 Comment The dose-spacing between the mid and high dose was very large","dose":"at week 6 in the middle and the high dose group and at week 13 in the high dose group only, calcium levels were increased in males and females at week 6 in the middle and the high dose group.","effect":"at week 6 in the middle and the high dose group and at week 13 in the high dose group only, calcium levels were increased in males and females at week 6 in the middle and the high dose group. Liver and kidney weights of males were increased in the high dose group. With the exception of inflammatory changes found in several organs in treated and control groups no relevant morphological changes were revealed. After the recovery period no differences in haematology, clinical chemistry and organ weights were seen. The NOAEL is 50 mg/kg bw/day, the NOEL 5 mg/kg bw/day. Ref.: 6 Comment The dose-spacing between the mid and high dose was very large. Guideline: OECD 408 (1998) Species/strain: rat, Wistar Hannover (HsdBrlHan:Wist) Group size: 120 (10 males and 10 females per group; control and high dose group: additional 5 males and 5 females for 4 weeks of recovery) Test substance: B034 Batch: DALA 013106 (SAT 040411) Purity: 99.5%","page":15,"pdf":"sccs_o_096.pdf","row_type":"noael_study","study_id":"sccs_o_096_noael_001"}
SCCS_vision_codex	NOAEL	=5	mg/kg bw/day	rat	-	4 weeks	NOAEL study	{"citation":"Ref.: 6 Comment The dose-spacing between the mid and high dose was very large","dose":"e high dose group and at week 13 in the high dose group only, calcium levels were increased in males and females at week 6 in the middle and the high dose group.","effect":"e high dose group and at week 13 in the high dose group only, calcium levels were increased in males and females at week 6 in the middle and the high dose group. Liver and kidney weights of males were increased in the high dose group. With the exception of inflammatory changes found in several organs in treated and control groups no relevant morphological changes were revealed. After the recovery period no differences in haematology, clinical chemistry and organ weights were seen. The NOAEL is 50 mg/kg bw/day, the NOEL 5 mg/kg bw/day. Ref.: 6 Comment The dose-spacing between the mid and high dose was very large. Guideline: OECD 408 (1998) Species/strain: rat, Wistar Hannover (HsdBrlHan:Wist) Group size: 120 (10 males and 10 females per group; control and high dose group: additional 5 males and 5 females for 4 weeks of recovery) Test substance: B034 Batch: DALA 013106 (SAT 040411) Purity: 99.5%","page":15,"pdf":"sccs_o_096.pdf","row_type":"noael_study","study_id":"sccs_o_096_noael_002"}
SCCS_vision_codex	NOAEL	=1000	mg/kg	rat	oral	Prenatal	developmental toxicity	{"citation":"Ref.: 21 Prenatal developmental study Guideline: OECD 414 (2001) Species/strain: rat, Wistar Hannover (HsdBrlHan:Wist) Group size: 100 (25 females per dose group) Test substance: B034 Ba","dose":"SCCS/1463/12 Opinion on N,N'-bis-(2-Hydroxyethyl)-2-nitro-p-phenylenediamine ___________________________________________________________________________________________ 32 unaffected in all dose groups.","effect":"SCCS/1463/12 Opinion on N,N'-bis-(2-Hydroxyethyl)-2-nitro-p-phenylenediamine ___________________________________________________________________________________________ 32 unaffected in all dose groups. The incidence of external, visceral, major and minor skeletal abnormalities was not changed by substance treatment. N,N’-bis-(2- hydroxyethyl)-2-nitro- p-phenylenediamine elicited maternal toxicity at 1000 mg/kg, the NOAEL in this study is 100 mg/kg bw/day. The NOAEL of embryotoxicity and teratogenicity is 1000 mg/kg bw/day. Ref.: 21 Prenatal developmental study Guideline: OECD 414 (2001) Species/strain: rat, Wistar Hannover (HsdBrlHan:Wist) Group size: 100 (25 females per dose group) Test substance: B034 Batch: DALA 013106 (SAT 040411) Purity: 99.5% Vehicle: 0.5% aqueous carboxymethylcellulose Dose levels: 0, 300, 600 and 1200 mg/kg bw Dose volume: 10 ml/kg bw Route: oral gavage Administration: once daily from gestation day (GD)","page":32,"pdf":"sccs_o_096.pdf","row_type":"noael_study","study_id":"sccs_o_096_noael_006"}
SCCS_vision_codex	NOAEL	=100	mg/kg bw/day	rat	oral	Prenatal	developmental toxicity	{"citation":"Ref.: 21 Prenatal developmental study Guideline: OECD 414 (2001) Species/strain: rat, Wistar Hannover (HsdBrlHan:Wist) Group size: 100 (25 females per dose group) Test substance: B034 Ba","dose":"SCCS/1463/12 Opinion on N,N'-bis-(2-Hydroxyethyl)-2-nitro-p-phenylenediamine ___________________________________________________________________________________________ 32 unaffected in all dose groups.","effect":"SCCS/1463/12 Opinion on N,N'-bis-(2-Hydroxyethyl)-2-nitro-p-phenylenediamine ___________________________________________________________________________________________ 32 unaffected in all dose groups. The incidence of external, visceral, major and minor skeletal abnormalities was not changed by substance treatment. N,N’-bis-(2- hydroxyethyl)-2-nitro- p-phenylenediamine elicited maternal toxicity at 1000 mg/kg, the NOAEL in this study is 100 mg/kg bw/day. The NOAEL of embryotoxicity and teratogenicity is 1000 mg/kg bw/day. Ref.: 21 Prenatal developmental study Guideline: OECD 414 (2001) Species/strain: rat, Wistar Hannover (HsdBrlHan:Wist) Group size: 100 (25 females per dose group) Test substance: B034 Batch: DALA 013106 (SAT 040411) Purity: 99.5% Vehicle: 0.5% aqueous carboxymethylcellulose Dose levels: 0, 300, 600 and 1200 mg/kg bw Dose volume: 10 ml/kg bw Route: oral gavage Administration: once daily from gestation day (GD) 5 through day 19 GLP statement: in complianc","page":32,"pdf":"sccs_o_096.pdf","row_type":"noael_study","study_id":"sccs_o_096_noael_007"}
SCCS_vision_codex	NOAEL	=720	mg/kg bw/day	mouse	-	90 day	irritation	{"dose":"The No Observed Adverse Effect Level (NOAEL) for N,N’-bis-(2-hydroxyethyl)-2-nitro-p- phenylenediamine in the 90 day study was considered to be 240 mg/kg bw/day, based on effects on kidney and urea at 720 mg/kg bw/day, which seemed to be the target organ.","effect":"________________________________________________ 35 Toxicity No mortalities occurred up to 5 g/kg bw, so N,N’-bis-(2-hydroxyethyl)-2-nitro-p- phenylenediamine showed no acute toxicity. The No Observed Adverse Effect Level (NOAEL) for N,N’-bis-(2-hydroxyethyl)-2-nitro-p- phenylenediamine in the 90 day study was considered to be 240 mg/kg bw/day, based on effects on kidney and urea at 720 mg/kg bw/day, which seemed to be the target organ. Since no maternal toxicity, foetal toxicity or teratogenicity was seen, the No Observed Adverse Effect Level (NOAEL) for N,N’-bis-(2-hydroxyethyl)-2-nitro-p-phenylenediamine for these endpoints was considered to be 1200 mg/kg/day. Skin/eye irritation and sensitisation Neat N,N’-bis-(2-hydroxyethyl)-2-nitro-p-phenylenediamine was not irritant when applied to rabbit skin. However, it was noted that 10% N,N’-bis-(2-hydroxyethyl)-2-nitro-p- phenylenediamine in acetone:olive oil was slightly irritant to the mouse ear in the LLNA test. It was irritant to rabbit eyes. N,N’-bis-(2-hydroxyethyl)-2-nitro-p-phenylenediamine was n","page":35,"pdf":"sccs_o_096.pdf","row_type":"noael_study","study_id":"sccs_o_096_noael_011"}
SCCS_vision_codex	NOAEL	=0.017	mg/kg bw/d	rat	oral	90-day	dermal absorption	{"dose":"___________________________________________________________________________ 36 No data submitted 3.3.12 Special investigations 3.3.13 Safety evaluation (including calculation of the MoS) CALCULATION OF THE MARGIN OF SAFETY (Oxidative conditions) (on head concentration 1%) Absorption through the skin A = 1.76 µg/cm² Skin Area surface SAS = 580 cm...","effect":"___________________________________________________________________________ 36 No data submitted 3.3.12 Special investigations 3.3.13 Safety evaluation (including calculation of the MoS) CALCULATION OF THE MARGIN OF SAFETY (Oxidative conditions) (on head concentration 1%) Absorption through the skin A = 1.76 µg/cm² Skin Area surface SAS = 580 cm2 Dermal absorption per treatment SAS x A x 0.001 = 1.021 mg Typical body weight of human = 60 kg Systemic exposure dose (SED) SAS x A x 0.001/60 = 0.017 mg/kg bw/d No observed adverse effect level NOAEL = 240 mg/kg bw/d (90-day, oral, rat) Bioavailability 50%* = 120 mg/kg bw/d Margin of Safety adjusted NOAEL/SED = 7100 * standard procedure according to the SCCS's Notes of Guidance for the testing of cosmetic ingredients and their safety evaluation. (Non-oxidative conditions) (on head concentration 1.5%) Absorption through the skin A = 2.97 µg/cm² Skin Area surface SAS = 580 cm2 Dermal absorption per treatment SAS x A x 0.001 = 1.723 mg Typical body weight of human = 60 kg Systemic exposure dose (SED)","page":36,"pdf":"sccs_o_196.pdf","row_type":"noael_study","study_id":"sccs_o_196_noael_010"}
SCCS_vision_codex	NOAEL	=240	mg/kg bw/d	rat	oral	90-day	dermal absorption	{"dose":"__________________________________________ 36 No data submitted 3.3.12 Special investigations 3.3.13 Safety evaluation (including calculation of the MoS) CALCULATION OF THE MARGIN OF SAFETY (Oxidative conditions) (on head concentration 1%) Absorption through the skin A = 1.76 µg/cm² Skin Area surface SAS = 580 cm2 Dermal absorption per treatment...","effect":"__________________________________________ 36 No data submitted 3.3.12 Special investigations 3.3.13 Safety evaluation (including calculation of the MoS) CALCULATION OF THE MARGIN OF SAFETY (Oxidative conditions) (on head concentration 1%) Absorption through the skin A = 1.76 µg/cm² Skin Area surface SAS = 580 cm2 Dermal absorption per treatment SAS x A x 0.001 = 1.021 mg Typical body weight of human = 60 kg Systemic exposure dose (SED) SAS x A x 0.001/60 = 0.017 mg/kg bw/d No observed adverse effect level NOAEL = 240 mg/kg bw/d (90-day, oral, rat) Bioavailability 50%* = 120 mg/kg bw/d Margin of Safety adjusted NOAEL/SED = 7100 * standard procedure according to the SCCS's Notes of Guidance for the testing of cosmetic ingredients and their safety evaluation. (Non-oxidative conditions) (on head concentration 1.5%) Absorption through the skin A = 2.97 µg/cm² Skin Area surface SAS = 580 cm2 Dermal absorption per treatment SAS x A x 0.001 = 1.723 mg Typical body weight of human = 60 kg Systemic exposure dose (SED) SAS x","page":36,"pdf":"sccs_o_196.pdf","row_type":"noael_study","study_id":"sccs_o_196_noael_011"}
SCCS_vision_codex	NOAEL	=120	mg/kg bw/d	rat	oral	90-day	dermal absorption	{"dose":"ty evaluation (including calculation of the MoS) CALCULATION OF THE MARGIN OF SAFETY (Oxidative conditions) (on head concentration 1%) Absorption through the skin A = 1.76 µg/cm² Skin Area surface SAS = 580 cm2 Dermal absorption per treatment SAS x A x 0.001 = 1.021 mg Typical body weight of human = 60 kg Systemic exposure dose (SED) SAS x A x 0...","effect":"ty evaluation (including calculation of the MoS) CALCULATION OF THE MARGIN OF SAFETY (Oxidative conditions) (on head concentration 1%) Absorption through the skin A = 1.76 µg/cm² Skin Area surface SAS = 580 cm2 Dermal absorption per treatment SAS x A x 0.001 = 1.021 mg Typical body weight of human = 60 kg Systemic exposure dose (SED) SAS x A x 0.001/60 = 0.017 mg/kg bw/d No observed adverse effect level NOAEL = 240 mg/kg bw/d (90-day, oral, rat) Bioavailability 50%* = 120 mg/kg bw/d Margin of Safety adjusted NOAEL/SED = 7100 * standard procedure according to the SCCS's Notes of Guidance for the testing of cosmetic ingredients and their safety evaluation. (Non-oxidative conditions) (on head concentration 1.5%) Absorption through the skin A = 2.97 µg/cm² Skin Area surface SAS = 580 cm2 Dermal absorption per treatment SAS x A x 0.001 = 1.723 mg Typical body weight of human = 60 kg Systemic exposure dose (SED) SAS x A x 0.001/60 = 0.029 mg/kg bw/d No observed adverse effect level NOAEL = 240 mg/kg bw/d (90-day, oral, rat)","page":36,"pdf":"sccs_o_196.pdf","row_type":"noael_study","study_id":"sccs_o_196_noael_012"}
SCCS_vision_codex	NOAEL	=0.029	mg/kg bw/d	rat	oral	90-day	dermal absorption	{"dose":"rat) Bioavailability 50%* = 120 mg/kg bw/d Margin of Safety adjusted NOAEL/SED = 7100 * standard procedure according to the SCCS's Notes of Guidance for the testing of cosmetic ingredients and their safety evaluation.","effect":"rat) Bioavailability 50%* = 120 mg/kg bw/d Margin of Safety adjusted NOAEL/SED = 7100 * standard procedure according to the SCCS's Notes of Guidance for the testing of cosmetic ingredients and their safety evaluation. (Non-oxidative conditions) (on head concentration 1.5%) Absorption through the skin A = 2.97 µg/cm² Skin Area surface SAS = 580 cm2 Dermal absorption per treatment SAS x A x 0.001 = 1.723 mg Typical body weight of human = 60 kg Systemic exposure dose (SED) SAS x A x 0.001/60 = 0.029 mg/kg bw/d No observed adverse effect level NOAEL = 240 mg/kg bw/d (90-day, oral, rat) Bioavailability 50%* = 120 mg/kg bw/d Margin of Safety adjusted NOAEL/SED = 4100 * standard procedure according to the SCCS's Notes of Guidance for the testing of cosmetic ingredients and their safety evaluation. 3.3.14 Discussion Physico-chemical properties N,N’-bis-(2-hydroxyethyl)-2-nitro-p-phenylenediamine is used as a direct hair dye for hair colouring products. It is also used in oxidative hair dye formulations with and without an oxidising agent (e.g. hydrog","page":36,"pdf":"sccs_o_196.pdf","row_type":"noael_study","study_id":"sccs_o_196_noael_013"}
SCCS_vision_codex	NOAEL	=0.017	mg/kg bw/d	rat	oral	90-day	dermal absorption	{"dose":"___________________________________________________________________________ 36 No data submitted 3.3.12 Special investigations 3.3.13 Safety evaluation (including calculation of the MoS) CALCULATION OF THE MARGIN OF SAFETY (Oxidative conditions) (on head concentration 1%) Absorption through the skin A = 1.76 µg/cm² Skin Area surface SAS = 580 cm...","effect":"___________________________________________________________________________ 36 No data submitted 3.3.12 Special investigations 3.3.13 Safety evaluation (including calculation of the MoS) CALCULATION OF THE MARGIN OF SAFETY (Oxidative conditions) (on head concentration 1%) Absorption through the skin A = 1.76 µg/cm² Skin Area surface SAS = 580 cm2 Dermal absorption per treatment SAS x A x 0.001 = 1.021 mg Typical body weight of human = 60 kg Systemic exposure dose (SED) SAS x A x 0.001/60 = 0.017 mg/kg bw/d No observed adverse effect level NOAEL = 240 mg/kg bw/d (90-day, oral, rat) Bioavailability 50%* = 120 mg/kg bw/d Margin of Safety adjusted NOAEL/SED = 7100 * standard procedure according to the SCCS's Notes of Guidance for the testing of cosmetic ingredients and their safety evaluation. (Non-oxidative conditions) (on head concentration 1.5%) Absorption through the skin A = 2.97 µg/cm² Skin Area surface SAS = 580 cm2 Dermal absorption per treatment SAS x A x 0.001 = 1.723 mg Typical body weight of human = 60 kg Systemic exposure dose (SED)","page":36,"pdf":"sccs_o_196.pdf","row_type":"noael_study","study_id":"sccs_o_196_noael_010"}
SCCS_vision_codex	NOAEL	=240	mg/kg bw/d	rat	oral	90-day	dermal absorption	{"dose":"__________________________________________ 36 No data submitted 3.3.12 Special investigations 3.3.13 Safety evaluation (including calculation of the MoS) CALCULATION OF THE MARGIN OF SAFETY (Oxidative conditions) (on head concentration 1%) Absorption through the skin A = 1.76 µg/cm² Skin Area surface SAS = 580 cm2 Dermal absorption per treatment...","effect":"__________________________________________ 36 No data submitted 3.3.12 Special investigations 3.3.13 Safety evaluation (including calculation of the MoS) CALCULATION OF THE MARGIN OF SAFETY (Oxidative conditions) (on head concentration 1%) Absorption through the skin A = 1.76 µg/cm² Skin Area surface SAS = 580 cm2 Dermal absorption per treatment SAS x A x 0.001 = 1.021 mg Typical body weight of human = 60 kg Systemic exposure dose (SED) SAS x A x 0.001/60 = 0.017 mg/kg bw/d No observed adverse effect level NOAEL = 240 mg/kg bw/d (90-day, oral, rat) Bioavailability 50%* = 120 mg/kg bw/d Margin of Safety adjusted NOAEL/SED = 7100 * standard procedure according to the SCCS's Notes of Guidance for the testing of cosmetic ingredients and their safety evaluation. (Non-oxidative conditions) (on head concentration 1.5%) Absorption through the skin A = 2.97 µg/cm² Skin Area surface SAS = 580 cm2 Dermal absorption per treatment SAS x A x 0.001 = 1.723 mg Typical body weight of human = 60 kg Systemic exposure dose (SED) SAS x","page":36,"pdf":"sccs_o_196.pdf","row_type":"noael_study","study_id":"sccs_o_196_noael_011"}
SCCS_vision_codex	NOAEL	=120	mg/kg bw/d	rat	oral	90-day	dermal absorption	{"dose":"ty evaluation (including calculation of the MoS) CALCULATION OF THE MARGIN OF SAFETY (Oxidative conditions) (on head concentration 1%) Absorption through the skin A = 1.76 µg/cm² Skin Area surface SAS = 580 cm2 Dermal absorption per treatment SAS x A x 0.001 = 1.021 mg Typical body weight of human = 60 kg Systemic exposure dose (SED) SAS x A x 0...","effect":"ty evaluation (including calculation of the MoS) CALCULATION OF THE MARGIN OF SAFETY (Oxidative conditions) (on head concentration 1%) Absorption through the skin A = 1.76 µg/cm² Skin Area surface SAS = 580 cm2 Dermal absorption per treatment SAS x A x 0.001 = 1.021 mg Typical body weight of human = 60 kg Systemic exposure dose (SED) SAS x A x 0.001/60 = 0.017 mg/kg bw/d No observed adverse effect level NOAEL = 240 mg/kg bw/d (90-day, oral, rat) Bioavailability 50%* = 120 mg/kg bw/d Margin of Safety adjusted NOAEL/SED = 7100 * standard procedure according to the SCCS's Notes of Guidance for the testing of cosmetic ingredients and their safety evaluation. (Non-oxidative conditions) (on head concentration 1.5%) Absorption through the skin A = 2.97 µg/cm² Skin Area surface SAS = 580 cm2 Dermal absorption per treatment SAS x A x 0.001 = 1.723 mg Typical body weight of human = 60 kg Systemic exposure dose (SED) SAS x A x 0.001/60 = 0.029 mg/kg bw/d No observed adverse effect level NOAEL = 240 mg/kg bw/d (90-day, oral, rat)","page":36,"pdf":"sccs_o_196.pdf","row_type":"noael_study","study_id":"sccs_o_196_noael_012"}
SCCS_vision_codex	NOAEL	=0.029	mg/kg bw/d	rat	oral	90-day	dermal absorption	{"dose":"rat) Bioavailability 50%* = 120 mg/kg bw/d Margin of Safety adjusted NOAEL/SED = 7100 * standard procedure according to the SCCS's Notes of Guidance for the testing of cosmetic ingredients and their safety evaluation.","effect":"rat) Bioavailability 50%* = 120 mg/kg bw/d Margin of Safety adjusted NOAEL/SED = 7100 * standard procedure according to the SCCS's Notes of Guidance for the testing of cosmetic ingredients and their safety evaluation. (Non-oxidative conditions) (on head concentration 1.5%) Absorption through the skin A = 2.97 µg/cm² Skin Area surface SAS = 580 cm2 Dermal absorption per treatment SAS x A x 0.001 = 1.723 mg Typical body weight of human = 60 kg Systemic exposure dose (SED) SAS x A x 0.001/60 = 0.029 mg/kg bw/d No observed adverse effect level NOAEL = 240 mg/kg bw/d (90-day, oral, rat) Bioavailability 50%* = 120 mg/kg bw/d Margin of Safety adjusted NOAEL/SED = 4100 * standard procedure according to the SCCS's Notes of Guidance for the testing of cosmetic ingredients and their safety evaluation. 3.3.14 Discussion Physico-chemical properties N,N’-bis-(2-hydroxyethyl)-2-nitro-p-phenylenediamine is used as a direct hair dye for hair colouring products. It is also used in oxidative hair dye formulations with and without an oxidising agent (e.g. hydrog","page":36,"pdf":"sccs_o_196.pdf","row_type":"noael_study","study_id":"sccs_o_196_noael_013"}
SCCS_vision_codex	NOAEL	=240	mg/kg/day	-	-	Chronic	genotoxicity	{"citation":"Ref.: 11 3","dose":"SCCS/1228/09, revision of 12.07.10 Opinion on N,N'-bis-(2-Hydroxyethyl)-2-nitro-p-phenylenediamine __________________________________________________________________________________ 16 Conclusion On the basis of these results, the mid-dose (240 mg/kg/day) may be considered the No Observed Adverse Effect Level (NOAEL) for N,N’-bis-(2-hydroxyethyl...","effect":"SCCS/1228/09, revision of 12.07.10 Opinion on N,N'-bis-(2-Hydroxyethyl)-2-nitro-p-phenylenediamine __________________________________________________________________________________ 16 Conclusion On the basis of these results, the mid-dose (240 mg/kg/day) may be considered the No Observed Adverse Effect Level (NOAEL) for N,N’-bis-(2-hydroxyethyl)-2-nitro-p- phenylenediamine. Ref.: 11 3.3.5.3. Chronic (> 12 months) toxicity No data submitted 3.3.6. Mutagenicity / Genotoxicity 3.3.6.1 Mutagenicity / Genotoxicity in vitro Taken from SCCNFP/0781/04 Reverse Mutation Testing Using Bacteria Guideline: OECD 471 (1983) Species/Strain: Salmonella typhimurium (TA98, TA98 NR) Test item: HC Violet B5 Batch: / Purity: / Replicate: 2 experiments Doses: 100, 500, 1000, 2500, 5000, 7500, 10000 μg/plate Metabolic Act.: Phenobarbi","page":16,"pdf":"sccs_o_019.pdf","row_type":"noael_study","study_id":"sccs_o_019_noael_001"}
SCCS_vision_codex	NOAEL	=1200	mg/kg/day	human	-	-	NOAEL study	{"citation":"Ref.: 12 3","dose":"cantly increase in the percentage of male foetuses noted in the low dose group was not considered to be of toxicological significance.","effect":"cantly increase in the percentage of male foetuses noted in the low dose group was not considered to be of toxicological significance. The number of small foetuses was comparable between groups. No relevance was attributed to the minor anomalies noted in one low dose foetus. Visceral examination did not show any dose related findings. No relevant foetal treatment- related skeletal changes were reported. Conclusion No maternal toxicity, foetal toxicity or teratogenicity was seen. On the basis of these results, the No Observed Adverse Effect Level (NOAEL) for N,N’-bis-(2-hydroxyethyl)-2- nitro-p-phenylenediamine should be considered to be 1200 mg/kg/day. Ref.: 12 3.3.9. Toxicokinetics No data submitted 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 3.3.13. Safety evaluation (including calculation of the MoS) CAL","page":27,"pdf":"sccs_o_019.pdf","row_type":"noael_study","study_id":"sccs_o_019_noael_002"}
SCCS_vision_codex	NOAEL	=50	mg/kg bw/day	rat	-	4 weeks	NOAEL study	{"citation":"Ref.: 6 Comment The dose-spacing between the mid and high dose was very large","dose":"at week 6 in the middle and the high dose group and at week 13 in the high dose group only, calcium levels were increased in males and females at week 6 in the middle and the high dose group.","effect":"at week 6 in the middle and the high dose group and at week 13 in the high dose group only, calcium levels were increased in males and females at week 6 in the middle and the high dose group. Liver and kidney weights of males were increased in the high dose group. With the exception of inflammatory changes found in several organs in treated and control groups no relevant morphological changes were revealed. After the recovery period no differences in haematology, clinical chemistry and organ weights were seen. The NOAEL is 50 mg/kg bw/day, the NOEL 5 mg/kg bw/day. Ref.: 6 Comment The dose-spacing between the mid and high dose was very large. Guideline: OECD 408 (1998) Species/strain: rat, Wistar Hannover (HsdBrlHan:Wist) Group size: 120 (10 males and 10 females per group; control and high dose group: additional 5 males and 5 females for 4 weeks of recovery) Test substance: B034 Batch: DALA 013106 (SAT 040411) Purity: 99.5%","page":15,"pdf":"sccs_o_096.pdf","row_type":"noael_study","study_id":"sccs_o_096_noael_001"}
SCCS_vision_codex	NOAEL	=5	mg/kg bw/day	rat	-	4 weeks	NOAEL study	{"citation":"Ref.: 6 Comment The dose-spacing between the mid and high dose was very large","dose":"e high dose group and at week 13 in the high dose group only, calcium levels were increased in males and females at week 6 in the middle and the high dose group.","effect":"e high dose group and at week 13 in the high dose group only, calcium levels were increased in males and females at week 6 in the middle and the high dose group. Liver and kidney weights of males were increased in the high dose group. With the exception of inflammatory changes found in several organs in treated and control groups no relevant morphological changes were revealed. After the recovery period no differences in haematology, clinical chemistry and organ weights were seen. The NOAEL is 50 mg/kg bw/day, the NOEL 5 mg/kg bw/day. Ref.: 6 Comment The dose-spacing between the mid and high dose was very large. Guideline: OECD 408 (1998) Species/strain: rat, Wistar Hannover (HsdBrlHan:Wist) Group size: 120 (10 males and 10 females per group; control and high dose group: additional 5 males and 5 females for 4 weeks of recovery) Test substance: B034 Batch: DALA 013106 (SAT 040411) Purity: 99.5%","page":15,"pdf":"sccs_o_096.pdf","row_type":"noael_study","study_id":"sccs_o_096_noael_002"}
SCCS_vision_codex	NOAEL	=1000	mg/kg	rat	oral	Prenatal	developmental toxicity	{"citation":"Ref.: 21 Prenatal developmental study Guideline: OECD 414 (2001) Species/strain: rat, Wistar Hannover (HsdBrlHan:Wist) Group size: 100 (25 females per dose group) Test substance: B034 Ba","dose":"SCCS/1463/12 Opinion on N,N'-bis-(2-Hydroxyethyl)-2-nitro-p-phenylenediamine ___________________________________________________________________________________________ 32 unaffected in all dose groups.","effect":"SCCS/1463/12 Opinion on N,N'-bis-(2-Hydroxyethyl)-2-nitro-p-phenylenediamine ___________________________________________________________________________________________ 32 unaffected in all dose groups. The incidence of external, visceral, major and minor skeletal abnormalities was not changed by substance treatment. N,N’-bis-(2- hydroxyethyl)-2-nitro- p-phenylenediamine elicited maternal toxicity at 1000 mg/kg, the NOAEL in this study is 100 mg/kg bw/day. The NOAEL of embryotoxicity and teratogenicity is 1000 mg/kg bw/day. Ref.: 21 Prenatal developmental study Guideline: OECD 414 (2001) Species/strain: rat, Wistar Hannover (HsdBrlHan:Wist) Group size: 100 (25 females per dose group) Test substance: B034 Batch: DALA 013106 (SAT 040411) Purity: 99.5% Vehicle: 0.5% aqueous carboxymethylcellulose Dose levels: 0, 300, 600 and 1200 mg/kg bw Dose volume: 10 ml/kg bw Route: oral gavage Administration: once daily from gestation day (GD)","page":32,"pdf":"sccs_o_096.pdf","row_type":"noael_study","study_id":"sccs_o_096_noael_006"}
SCCS_vision_codex	NOAEL	=100	mg/kg bw/day	rat	oral	Prenatal	developmental toxicity	{"citation":"Ref.: 21 Prenatal developmental study Guideline: OECD 414 (2001) Species/strain: rat, Wistar Hannover (HsdBrlHan:Wist) Group size: 100 (25 females per dose group) Test substance: B034 Ba","dose":"SCCS/1463/12 Opinion on N,N'-bis-(2-Hydroxyethyl)-2-nitro-p-phenylenediamine ___________________________________________________________________________________________ 32 unaffected in all dose groups.","effect":"SCCS/1463/12 Opinion on N,N'-bis-(2-Hydroxyethyl)-2-nitro-p-phenylenediamine ___________________________________________________________________________________________ 32 unaffected in all dose groups. The incidence of external, visceral, major and minor skeletal abnormalities was not changed by substance treatment. N,N’-bis-(2- hydroxyethyl)-2-nitro- p-phenylenediamine elicited maternal toxicity at 1000 mg/kg, the NOAEL in this study is 100 mg/kg bw/day. The NOAEL of embryotoxicity and teratogenicity is 1000 mg/kg bw/day. Ref.: 21 Prenatal developmental study Guideline: OECD 414 (2001) Species/strain: rat, Wistar Hannover (HsdBrlHan:Wist) Group size: 100 (25 females per dose group) Test substance: B034 Batch: DALA 013106 (SAT 040411) Purity: 99.5% Vehicle: 0.5% aqueous carboxymethylcellulose Dose levels: 0, 300, 600 and 1200 mg/kg bw Dose volume: 10 ml/kg bw Route: oral gavage Administration: once daily from gestation day (GD) 5 through day 19 GLP statement: in complianc","page":32,"pdf":"sccs_o_096.pdf","row_type":"noael_study","study_id":"sccs_o_096_noael_007"}
SCCS_vision_codex	NOAEL	=720	mg/kg bw/day	mouse	-	90 day	irritation	{"dose":"The No Observed Adverse Effect Level (NOAEL) for N,N’-bis-(2-hydroxyethyl)-2-nitro-p- phenylenediamine in the 90 day study was considered to be 240 mg/kg bw/day, based on effects on kidney and urea at 720 mg/kg bw/day, which seemed to be the target organ.","effect":"________________________________________________ 35 Toxicity No mortalities occurred up to 5 g/kg bw, so N,N’-bis-(2-hydroxyethyl)-2-nitro-p- phenylenediamine showed no acute toxicity. The No Observed Adverse Effect Level (NOAEL) for N,N’-bis-(2-hydroxyethyl)-2-nitro-p- phenylenediamine in the 90 day study was considered to be 240 mg/kg bw/day, based on effects on kidney and urea at 720 mg/kg bw/day, which seemed to be the target organ. Since no maternal toxicity, foetal toxicity or teratogenicity was seen, the No Observed Adverse Effect Level (NOAEL) for N,N’-bis-(2-hydroxyethyl)-2-nitro-p-phenylenediamine for these endpoints was considered to be 1200 mg/kg/day. Skin/eye irritation and sensitisation Neat N,N’-bis-(2-hydroxyethyl)-2-nitro-p-phenylenediamine was not irritant when applied to rabbit skin. However, it was noted that 10% N,N’-bis-(2-hydroxyethyl)-2-nitro-p- phenylenediamine in acetone:olive oil was slightly irritant to the mouse ear in the LLNA test. It was irritant to rabbit eyes. N,N’-bis-(2-hydroxyethyl)-2-nitro-p-phenylenediamine was n","page":35,"pdf":"sccs_o_096.pdf","row_type":"noael_study","study_id":"sccs_o_096_noael_011"}
SCCS_vision_codex	NOAEL	=0.017	mg/kg bw/d	rat	oral	90-day	dermal absorption	{"dose":"___________________________________________________________________________ 36 No data submitted 3.3.12 Special investigations 3.3.13 Safety evaluation (including calculation of the MoS) CALCULATION OF THE MARGIN OF SAFETY (Oxidative conditions) (on head concentration 1%) Absorption through the skin A = 1.76 µg/cm² Skin Area surface SAS = 580 cm...","effect":"___________________________________________________________________________ 36 No data submitted 3.3.12 Special investigations 3.3.13 Safety evaluation (including calculation of the MoS) CALCULATION OF THE MARGIN OF SAFETY (Oxidative conditions) (on head concentration 1%) Absorption through the skin A = 1.76 µg/cm² Skin Area surface SAS = 580 cm2 Dermal absorption per treatment SAS x A x 0.001 = 1.021 mg Typical body weight of human = 60 kg Systemic exposure dose (SED) SAS x A x 0.001/60 = 0.017 mg/kg bw/d No observed adverse effect level NOAEL = 240 mg/kg bw/d (90-day, oral, rat) Bioavailability 50%* = 120 mg/kg bw/d Margin of Safety adjusted NOAEL/SED = 7100 * standard procedure according to the SCCS's Notes of Guidance for the testing of cosmetic ingredients and their safety evaluation. (Non-oxidative conditions) (on head concentration 1.5%) Absorption through the skin A = 2.97 µg/cm² Skin Area surface SAS = 580 cm2 Dermal absorption per treatment SAS x A x 0.001 = 1.723 mg Typical body weight of human = 60 kg Systemic exposure dose (SED)","page":36,"pdf":"sccs_o_196.pdf","row_type":"noael_study","study_id":"sccs_o_196_noael_010"}
SCCS_vision_codex	NOAEL	=240	mg/kg bw/d	rat	oral	90-day	dermal absorption	{"dose":"__________________________________________ 36 No data submitted 3.3.12 Special investigations 3.3.13 Safety evaluation (including calculation of the MoS) CALCULATION OF THE MARGIN OF SAFETY (Oxidative conditions) (on head concentration 1%) Absorption through the skin A = 1.76 µg/cm² Skin Area surface SAS = 580 cm2 Dermal absorption per treatment...","effect":"__________________________________________ 36 No data submitted 3.3.12 Special investigations 3.3.13 Safety evaluation (including calculation of the MoS) CALCULATION OF THE MARGIN OF SAFETY (Oxidative conditions) (on head concentration 1%) Absorption through the skin A = 1.76 µg/cm² Skin Area surface SAS = 580 cm2 Dermal absorption per treatment SAS x A x 0.001 = 1.021 mg Typical body weight of human = 60 kg Systemic exposure dose (SED) SAS x A x 0.001/60 = 0.017 mg/kg bw/d No observed adverse effect level NOAEL = 240 mg/kg bw/d (90-day, oral, rat) Bioavailability 50%* = 120 mg/kg bw/d Margin of Safety adjusted NOAEL/SED = 7100 * standard procedure according to the SCCS's Notes of Guidance for the testing of cosmetic ingredients and their safety evaluation. (Non-oxidative conditions) (on head concentration 1.5%) Absorption through the skin A = 2.97 µg/cm² Skin Area surface SAS = 580 cm2 Dermal absorption per treatment SAS x A x 0.001 = 1.723 mg Typical body weight of human = 60 kg Systemic exposure dose (SED) SAS x","page":36,"pdf":"sccs_o_196.pdf","row_type":"noael_study","study_id":"sccs_o_196_noael_011"}
SCCS_vision_codex	NOAEL	=120	mg/kg bw/d	rat	oral	90-day	dermal absorption	{"dose":"ty evaluation (including calculation of the MoS) CALCULATION OF THE MARGIN OF SAFETY (Oxidative conditions) (on head concentration 1%) Absorption through the skin A = 1.76 µg/cm² Skin Area surface SAS = 580 cm2 Dermal absorption per treatment SAS x A x 0.001 = 1.021 mg Typical body weight of human = 60 kg Systemic exposure dose (SED) SAS x A x 0...","effect":"ty evaluation (including calculation of the MoS) CALCULATION OF THE MARGIN OF SAFETY (Oxidative conditions) (on head concentration 1%) Absorption through the skin A = 1.76 µg/cm² Skin Area surface SAS = 580 cm2 Dermal absorption per treatment SAS x A x 0.001 = 1.021 mg Typical body weight of human = 60 kg Systemic exposure dose (SED) SAS x A x 0.001/60 = 0.017 mg/kg bw/d No observed adverse effect level NOAEL = 240 mg/kg bw/d (90-day, oral, rat) Bioavailability 50%* = 120 mg/kg bw/d Margin of Safety adjusted NOAEL/SED = 7100 * standard procedure according to the SCCS's Notes of Guidance for the testing of cosmetic ingredients and their safety evaluation. (Non-oxidative conditions) (on head concentration 1.5%) Absorption through the skin A = 2.97 µg/cm² Skin Area surface SAS = 580 cm2 Dermal absorption per treatment SAS x A x 0.001 = 1.723 mg Typical body weight of human = 60 kg Systemic exposure dose (SED) SAS x A x 0.001/60 = 0.029 mg/kg bw/d No observed adverse effect level NOAEL = 240 mg/kg bw/d (90-day, oral, rat)","page":36,"pdf":"sccs_o_196.pdf","row_type":"noael_study","study_id":"sccs_o_196_noael_012"}
SCCS_vision_codex	NOAEL	=0.029	mg/kg bw/d	rat	oral	90-day	dermal absorption	{"dose":"rat) Bioavailability 50%* = 120 mg/kg bw/d Margin of Safety adjusted NOAEL/SED = 7100 * standard procedure according to the SCCS's Notes of Guidance for the testing of cosmetic ingredients and their safety evaluation.","effect":"rat) Bioavailability 50%* = 120 mg/kg bw/d Margin of Safety adjusted NOAEL/SED = 7100 * standard procedure according to the SCCS's Notes of Guidance for the testing of cosmetic ingredients and their safety evaluation. (Non-oxidative conditions) (on head concentration 1.5%) Absorption through the skin A = 2.97 µg/cm² Skin Area surface SAS = 580 cm2 Dermal absorption per treatment SAS x A x 0.001 = 1.723 mg Typical body weight of human = 60 kg Systemic exposure dose (SED) SAS x A x 0.001/60 = 0.029 mg/kg bw/d No observed adverse effect level NOAEL = 240 mg/kg bw/d (90-day, oral, rat) Bioavailability 50%* = 120 mg/kg bw/d Margin of Safety adjusted NOAEL/SED = 4100 * standard procedure according to the SCCS's Notes of Guidance for the testing of cosmetic ingredients and their safety evaluation. 3.3.14 Discussion Physico-chemical properties N,N’-bis-(2-hydroxyethyl)-2-nitro-p-phenylenediamine is used as a direct hair dye for hair colouring products. It is also used in oxidative hair dye formulations with and without an oxidising agent (e.g. hydrog","page":36,"pdf":"sccs_o_196.pdf","row_type":"noael_study","study_id":"sccs_o_196_noael_013"}

UnifiedCodex:SCCNFP:beta.noael_studies 8 endpoints

Source	Endpoint Type	Value	Unit	Species	Route	Duration	Study Type	Reference
UnifiedCodex:SCCNFP:beta.noael_studies	dermal absorption	100	mg/kg bw/day	rat	dermal	-	dermal absorption	SOURCE_SUBDIR=out257_en; REPORT_TITLE=OPINION OF THE SCIENTIFIC COMMITTEE ON COSMETIC PRODUCTS AND NON-FOOD PRODUCTS INTENDED FOR CONSUMERS CONCERNING N,N’-BIS-(2-HYDROXYETHYL)-2-NITRO-P-PHENYLENEDIAMINE COLIPA n° B34; OPINION_NUMBER=SCCNFP/0781/04; COMMITTEE=SCCNFP; REPORT_DATE=adopted by the SCCNFP on 23 April 2004; VALUE_TEXT=100; DOSE=In the high dose group maternal food consumption and body weight gain was significantly reduced while the slightly lower body weight gain compared to controls in the 100 mg/kg bw/day group was not statistically significant.; EFFECT=treated groups. In the high dose group maternal food consumption and body weight gain was significantly reduced while the slightly lower body weight gain compared to controls in the 100 mg/kg bw/day group was not statistically significant. Reproduction parameters remained unaffected in all dose groups. The incidence of external, visceral, major and minor skeletal abnormalities was not changed by substance treatment. N,N’-bis-(2- hydroxyethyl)-2-nitro-p-phenylenediamine elicited maternal toxicity at 1000 mg/kg, the NOAEL in this study is 100 mg/kg bw/day. The NOAEL of embryotoxicity and teratogenicity is 1000 mg/kg bw/day. Ref.: 21 2.7. Toxicokinetics (incl. Percutaneous Absorption) Percutaneous penetration / dermal absorption of a hair dye formulation in rats Guideline : / Animal strain : Sprague Dawley rats (Him:OFA) 5 males and 5 females in each of 2 experiments Method : 14C ring labelled N,N’-bis-(2-hydroxyethyl)-2-nitro-p-phenylenediamine in a hair dye formulation (without developer), radiochemical purity > 98; CITATION=Ref.: 21 2; CITATION_NUMBERS=[21,2]; REFERENCE=Ref.: 21 2; DETAILS_JSON={"cas_number":"84041-77-0","citation":"Ref.: 21 2","dose":"In the high dose group maternal food consumption and body weight gain was significantly reduced while the slightly lower body weight gain compared to controls in the 100 mg/kg bw/day group was not statistically significant.","duration":"","effect":"treated groups. In the high dose group maternal food consumption and body weight gain was significantly reduced while the slightly lower body weight gain compared to controls in the 100 mg/kg bw/day group was not statistically significant. Reproduction parameters remained unaffected in all dose groups. The incidence of external, visceral, major and minor skeletal abnormalities was not changed by substance treatment. N,N’-bis-(2- hydroxyethyl)-2-nitro-p-phenylenediamine elicited maternal toxicity at 1000 mg/kg, the NOAEL in this study is 100 mg/kg bw/day. The NOAEL of embryotoxicity and teratogenicity is 1000 mg/kg bw/day. Ref.: 21 2.7. Toxicokinetics (incl. Percutaneous Absorption) Percutaneous penetration / dermal absorption of a hair dye formulation in rats Guideline : / Animal strain : Sprague Dawley rats (Him:OFA) 5 males and 5 females in each of 2 experiments Method : 14C ring labelled N,N’-bis-(2-hydroxyethyl)-2-nitro-p-phenylenediamine in a hair dye formulation (without developer), radiochemical purity > 98","endpoint":"dermal absorption","ingredient":"codes","loael_value":"","noael_unit":"mg/kg bw/day","noael_value":"100","page":9,"route":"dermal","species":"rat","study_id":"out257_en_noael_003"}
UnifiedCodex:SCCNFP:beta.noael_studies	dermal absorption	1000	mg/kg bw/day	rat	dermal	-	dermal absorption	SOURCE_SUBDIR=out257_en; REPORT_TITLE=OPINION OF THE SCIENTIFIC COMMITTEE ON COSMETIC PRODUCTS AND NON-FOOD PRODUCTS INTENDED FOR CONSUMERS CONCERNING N,N’-BIS-(2-HYDROXYETHYL)-2-NITRO-P-PHENYLENEDIAMINE COLIPA n° B34; OPINION_NUMBER=SCCNFP/0781/04; COMMITTEE=SCCNFP; REPORT_DATE=adopted by the SCCNFP on 23 April 2004; VALUE_TEXT=1000; DOSE=al food consumption and body weight gain was significantly reduced while the slightly lower body weight gain compared to controls in the 100 mg/kg bw/day group was not statistically significant.; EFFECT=al food consumption and body weight gain was significantly reduced while the slightly lower body weight gain compared to controls in the 100 mg/kg bw/day group was not statistically significant. Reproduction parameters remained unaffected in all dose groups. The incidence of external, visceral, major and minor skeletal abnormalities was not changed by substance treatment. N,N’-bis-(2- hydroxyethyl)-2-nitro-p-phenylenediamine elicited maternal toxicity at 1000 mg/kg, the NOAEL in this study is 100 mg/kg bw/day. The NOAEL of embryotoxicity and teratogenicity is 1000 mg/kg bw/day. Ref.: 21 2.7. Toxicokinetics (incl. Percutaneous Absorption) Percutaneous penetration / dermal absorption of a hair dye formulation in rats Guideline : / Animal strain : Sprague Dawley rats (Him:OFA) 5 males and 5 females in each of 2 experiments Method : 14C ring labelled N,N’-bis-(2-hydroxyethyl)-2-nitro-p-phenylenediamine in a hair dye formulation (without developer), radiochemical purity > 98 %, applied to the back skin for 30 minutes a; CITATION=Ref.: 21 2; CITATION_NUMBERS=[21,2]; REFERENCE=Ref.: 21 2; DETAILS_JSON={"cas_number":"84041-77-0","citation":"Ref.: 21 2","dose":"al food consumption and body weight gain was significantly reduced while the slightly lower body weight gain compared to controls in the 100 mg/kg bw/day group was not statistically significant.","duration":"","effect":"al food consumption and body weight gain was significantly reduced while the slightly lower body weight gain compared to controls in the 100 mg/kg bw/day group was not statistically significant. Reproduction parameters remained unaffected in all dose groups. The incidence of external, visceral, major and minor skeletal abnormalities was not changed by substance treatment. N,N’-bis-(2- hydroxyethyl)-2-nitro-p-phenylenediamine elicited maternal toxicity at 1000 mg/kg, the NOAEL in this study is 100 mg/kg bw/day. The NOAEL of embryotoxicity and teratogenicity is 1000 mg/kg bw/day. Ref.: 21 2.7. Toxicokinetics (incl. Percutaneous Absorption) Percutaneous penetration / dermal absorption of a hair dye formulation in rats Guideline : / Animal strain : Sprague Dawley rats (Him:OFA) 5 males and 5 females in each of 2 experiments Method : 14C ring labelled N,N’-bis-(2-hydroxyethyl)-2-nitro-p-phenylenediamine in a hair dye formulation (without developer), radiochemical purity > 98 %, applied to the back skin for 30 minutes a","endpoint":"dermal absorption","ingredient":"codes","loael_value":"","noael_unit":"mg/kg bw/day","noael_value":"1000","page":9,"route":"dermal","species":"rat","study_id":"out257_en_noael_004"}
UnifiedCodex:SCCNFP:beta.noael_studies	repeated dose toxicity	50	mg/kg bw/day	-	dermal	Sub-chronic	repeated dose toxicity	SOURCE_SUBDIR=out257_en; REPORT_TITLE=OPINION OF THE SCIENTIFIC COMMITTEE ON COSMETIC PRODUCTS AND NON-FOOD PRODUCTS INTENDED FOR CONSUMERS CONCERNING N,N’-BIS-(2-HYDROXYETHYL)-2-NITRO-P-PHENYLENEDIAMINE COLIPA n° B34; OPINION_NUMBER=SCCNFP/0781/04; COMMITTEE=SCCNFP; REPORT_DATE=adopted by the SCCNFP on 23 April 2004; VALUE_TEXT=50; DOSE=at week 6 in the middle and the high dose group and at week 13 in the high dose group only, calcium levels were increased in males and females at week 6 in the middle and the high dose group.; EFFECT=at week 6 in the middle and the high dose group and at week 13 in the high dose group only, calcium levels were increased in males and females at week 6 in the middle and the high dose group. Liver and kidney weights of males were increased in the high dose group. With the exception of inflammatory changes found in several organs in treated and control groups no relevant morphological changes were revealed. After the recovery period no differences in haematology, clinical chemistry and organ weights were seen. The NOAEL is 50 mg/kg bw/day, the NOEL 5 mg/kg bw/day. Ref.: 6 2.3.8. Sub-chronic dermal toxicity No data 2.3.9. Sub-chronic inhalation toxicity No data; CITATION=Ref.: 6 2; CITATION_NUMBERS=[6,2]; REFERENCE=Ref.: 6 2; DETAILS_JSON={"cas_number":"84041-77-0","citation":"Ref.: 6 2","dose":"at week 6 in the middle and the high dose group and at week 13 in the high dose group only, calcium levels were increased in males and females at week 6 in the middle and the high dose group.","duration":"Sub-chronic","effect":"at week 6 in the middle and the high dose group and at week 13 in the high dose group only, calcium levels were increased in males and females at week 6 in the middle and the high dose group. Liver and kidney weights of males were increased in the high dose group. With the exception of inflammatory changes found in several organs in treated and control groups no relevant morphological changes were revealed. After the recovery period no differences in haematology, clinical chemistry and organ weights were seen. The NOAEL is 50 mg/kg bw/day, the NOEL 5 mg/kg bw/day. Ref.: 6 2.3.8. Sub-chronic dermal toxicity No data 2.3.9. Sub-chronic inhalation toxicity No data","endpoint":"repeated dose toxicity","ingredient":"codes","loael_value":"","noael_unit":"mg/kg bw/day","noael_value":"50","page":6,"route":"dermal","species":"","study_id":"out257_en_noael_001"}
UnifiedCodex:SCCNFP:beta.noael_studies	repeated dose toxicity	5	mg/kg bw/day	-	dermal	Sub-chronic	repeated dose toxicity	SOURCE_SUBDIR=out257_en; REPORT_TITLE=OPINION OF THE SCIENTIFIC COMMITTEE ON COSMETIC PRODUCTS AND NON-FOOD PRODUCTS INTENDED FOR CONSUMERS CONCERNING N,N’-BIS-(2-HYDROXYETHYL)-2-NITRO-P-PHENYLENEDIAMINE COLIPA n° B34; OPINION_NUMBER=SCCNFP/0781/04; COMMITTEE=SCCNFP; REPORT_DATE=adopted by the SCCNFP on 23 April 2004; VALUE_TEXT=5; DOSE=e high dose group and at week 13 in the high dose group only, calcium levels were increased in males and females at week 6 in the middle and the high dose group.; EFFECT=e high dose group and at week 13 in the high dose group only, calcium levels were increased in males and females at week 6 in the middle and the high dose group. Liver and kidney weights of males were increased in the high dose group. With the exception of inflammatory changes found in several organs in treated and control groups no relevant morphological changes were revealed. After the recovery period no differences in haematology, clinical chemistry and organ weights were seen. The NOAEL is 50 mg/kg bw/day, the NOEL 5 mg/kg bw/day. Ref.: 6 2.3.8. Sub-chronic dermal toxicity No data 2.3.9. Sub-chronic inhalation toxicity No data; CITATION=Ref.: 6 2; CITATION_NUMBERS=[6,2]; REFERENCE=Ref.: 6 2; DETAILS_JSON={"cas_number":"84041-77-0","citation":"Ref.: 6 2","dose":"e high dose group and at week 13 in the high dose group only, calcium levels were increased in males and females at week 6 in the middle and the high dose group.","duration":"Sub-chronic","effect":"e high dose group and at week 13 in the high dose group only, calcium levels were increased in males and females at week 6 in the middle and the high dose group. Liver and kidney weights of males were increased in the high dose group. With the exception of inflammatory changes found in several organs in treated and control groups no relevant morphological changes were revealed. After the recovery period no differences in haematology, clinical chemistry and organ weights were seen. The NOAEL is 50 mg/kg bw/day, the NOEL 5 mg/kg bw/day. Ref.: 6 2.3.8. Sub-chronic dermal toxicity No data 2.3.9. Sub-chronic inhalation toxicity No data","endpoint":"repeated dose toxicity","ingredient":"codes","loael_value":"","noael_unit":"mg/kg bw/day","noael_value":"5","page":6,"route":"dermal","species":"","study_id":"out257_en_noael_002"}
UnifiedCodex:SCCNFP:beta.noael_studies	repeated dose toxicity	50	mg/kg bw/day	rabbit	oral	subchronic	repeated dose toxicity	SOURCE_SUBDIR=out257_en; REPORT_TITLE=OPINION OF THE SCIENTIFIC COMMITTEE ON COSMETIC PRODUCTS AND NON-FOOD PRODUCTS INTENDED FOR CONSUMERS CONCERNING N,N’-BIS-(2-HYDROXYETHYL)-2-NITRO-P-PHENYLENEDIAMINE COLIPA n° B34; OPINION_NUMBER=SCCNFP/0781/04; COMMITTEE=SCCNFP; REPORT_DATE=adopted by the SCCNFP on 23 April 2004; VALUE_TEXT=50; DOSE=In a subchronic oral toxicity study, the NOAEL was set at 50 mg/kg bw/day, the NOEL at 5 mg/kg bw/day.; EFFECT=is provided as to the chemical characterisation of N,N’-bis-(2- hydroxyethyl-2-nitro-p-phenylenediamine in the test material(s). Purity of the hair dye as well as the impurities in the test material(s) have not been fully characterised. Log Pow of the test material has not been reported. N,N’-bis-(2-hydroxyethyl)-2-nitro-p-phenylenediamine is a secondary amine, and thus, it is prone to nitrosation. No information is provided on the nitrosamine content in the test material. In a subchronic oral toxicity study, the NOAEL was set at 50 mg/kg bw/day, the NOEL at 5 mg/kg bw/day. The test substance elicited maternal toxicity at 1000 mg/kg, the NOAEL in this study was set at 100 mg/kg bw/day. The NOAEL of embryotoxicity and teratogenicity was set at 1000 mg/kg bw/day. A 1 % suspension of N,N’-bis-(2-hydroxyethyl)-2-nitro-p-phenylenediamine was neither irritating nor corrosive when applied to the rabbit skin under occlusive conditions. It was considered to be non-irritating to the eye. However, it cannot be excluded that N,N’-bis-(2- h; CITATION_NUMBERS=[]; DETAILS_JSON={"cas_number":"84041-77-0","citation":"","dose":"In a subchronic oral toxicity study, the NOAEL was set at 50 mg/kg bw/day, the NOEL at 5 mg/kg bw/day.","duration":"subchronic","effect":"is provided as to the chemical characterisation of N,N’-bis-(2- hydroxyethyl-2-nitro-p-phenylenediamine in the test material(s). Purity of the hair dye as well as the impurities in the test material(s) have not been fully characterised. Log Pow of the test material has not been reported. N,N’-bis-(2-hydroxyethyl)-2-nitro-p-phenylenediamine is a secondary amine, and thus, it is prone to nitrosation. No information is provided on the nitrosamine content in the test material. In a subchronic oral toxicity study, the NOAEL was set at 50 mg/kg bw/day, the NOEL at 5 mg/kg bw/day. The test substance elicited maternal toxicity at 1000 mg/kg, the NOAEL in this study was set at 100 mg/kg bw/day. The NOAEL of embryotoxicity and teratogenicity was set at 1000 mg/kg bw/day. A 1 % suspension of N,N’-bis-(2-hydroxyethyl)-2-nitro-p-phenylenediamine was neither irritating nor corrosive when applied to the rabbit skin under occlusive conditions. It was considered to be non-irritating to the eye. However, it cannot be excluded that N,N’-bis-(2- h","endpoint":"repeated dose toxicity","ingredient":"codes","loael_value":"","noael_unit":"mg/kg bw/day","noael_value":"50","page":18,"route":"oral","species":"rabbit","study_id":"out257_en_noael_005"}
UnifiedCodex:SCCNFP:beta.noael_studies	repeated dose toxicity	5	mg/kg bw/day	rabbit	oral	subchronic	repeated dose toxicity	SOURCE_SUBDIR=out257_en; REPORT_TITLE=OPINION OF THE SCIENTIFIC COMMITTEE ON COSMETIC PRODUCTS AND NON-FOOD PRODUCTS INTENDED FOR CONSUMERS CONCERNING N,N’-BIS-(2-HYDROXYETHYL)-2-NITRO-P-PHENYLENEDIAMINE COLIPA n° B34; OPINION_NUMBER=SCCNFP/0781/04; COMMITTEE=SCCNFP; REPORT_DATE=adopted by the SCCNFP on 23 April 2004; VALUE_TEXT=5; DOSE=In a subchronic oral toxicity study, the NOAEL was set at 50 mg/kg bw/day, the NOEL at 5 mg/kg bw/day.; EFFECT=erisation of N,N’-bis-(2- hydroxyethyl-2-nitro-p-phenylenediamine in the test material(s). Purity of the hair dye as well as the impurities in the test material(s) have not been fully characterised. Log Pow of the test material has not been reported. N,N’-bis-(2-hydroxyethyl)-2-nitro-p-phenylenediamine is a secondary amine, and thus, it is prone to nitrosation. No information is provided on the nitrosamine content in the test material. In a subchronic oral toxicity study, the NOAEL was set at 50 mg/kg bw/day, the NOEL at 5 mg/kg bw/day. The test substance elicited maternal toxicity at 1000 mg/kg, the NOAEL in this study was set at 100 mg/kg bw/day. The NOAEL of embryotoxicity and teratogenicity was set at 1000 mg/kg bw/day. A 1 % suspension of N,N’-bis-(2-hydroxyethyl)-2-nitro-p-phenylenediamine was neither irritating nor corrosive when applied to the rabbit skin under occlusive conditions. It was considered to be non-irritating to the eye. However, it cannot be excluded that N,N’-bis-(2- hydroxyethyl)-2-nitro-p-phenylenediami; CITATION_NUMBERS=[]; DETAILS_JSON={"cas_number":"84041-77-0","citation":"","dose":"In a subchronic oral toxicity study, the NOAEL was set at 50 mg/kg bw/day, the NOEL at 5 mg/kg bw/day.","duration":"subchronic","effect":"erisation of N,N’-bis-(2- hydroxyethyl-2-nitro-p-phenylenediamine in the test material(s). Purity of the hair dye as well as the impurities in the test material(s) have not been fully characterised. Log Pow of the test material has not been reported. N,N’-bis-(2-hydroxyethyl)-2-nitro-p-phenylenediamine is a secondary amine, and thus, it is prone to nitrosation. No information is provided on the nitrosamine content in the test material. In a subchronic oral toxicity study, the NOAEL was set at 50 mg/kg bw/day, the NOEL at 5 mg/kg bw/day. The test substance elicited maternal toxicity at 1000 mg/kg, the NOAEL in this study was set at 100 mg/kg bw/day. The NOAEL of embryotoxicity and teratogenicity was set at 1000 mg/kg bw/day. A 1 % suspension of N,N’-bis-(2-hydroxyethyl)-2-nitro-p-phenylenediamine was neither irritating nor corrosive when applied to the rabbit skin under occlusive conditions. It was considered to be non-irritating to the eye. However, it cannot be excluded that N,N’-bis-(2- hydroxyethyl)-2-nitro-p-phenylenediami","endpoint":"repeated dose toxicity","ingredient":"codes","loael_value":"","noael_unit":"mg/kg bw/day","noael_value":"5","page":18,"route":"oral","species":"rabbit","study_id":"out257_en_noael_006"}
UnifiedCodex:SCCNFP:beta.noael_studies	repeated dose toxicity	100	mg/kg bw/day	rabbit	oral	subchronic	repeated dose toxicity	SOURCE_SUBDIR=out257_en; REPORT_TITLE=OPINION OF THE SCIENTIFIC COMMITTEE ON COSMETIC PRODUCTS AND NON-FOOD PRODUCTS INTENDED FOR CONSUMERS CONCERNING N,N’-BIS-(2-HYDROXYETHYL)-2-NITRO-P-PHENYLENEDIAMINE COLIPA n° B34; OPINION_NUMBER=SCCNFP/0781/04; COMMITTEE=SCCNFP; REPORT_DATE=adopted by the SCCNFP on 23 April 2004; VALUE_TEXT=100; DOSE=In a subchronic oral toxicity study, the NOAEL was set at 50 mg/kg bw/day, the NOEL at 5 mg/kg bw/day.; EFFECT=. Purity of the hair dye as well as the impurities in the test material(s) have not been fully characterised. Log Pow of the test material has not been reported. N,N’-bis-(2-hydroxyethyl)-2-nitro-p-phenylenediamine is a secondary amine, and thus, it is prone to nitrosation. No information is provided on the nitrosamine content in the test material. In a subchronic oral toxicity study, the NOAEL was set at 50 mg/kg bw/day, the NOEL at 5 mg/kg bw/day. The test substance elicited maternal toxicity at 1000 mg/kg, the NOAEL in this study was set at 100 mg/kg bw/day. The NOAEL of embryotoxicity and teratogenicity was set at 1000 mg/kg bw/day. A 1 % suspension of N,N’-bis-(2-hydroxyethyl)-2-nitro-p-phenylenediamine was neither irritating nor corrosive when applied to the rabbit skin under occlusive conditions. It was considered to be non-irritating to the eye. However, it cannot be excluded that N,N’-bis-(2- hydroxyethyl)-2-nitro-p-phenylenediamine has sensitization potential. The mean percutaneous absorption of the test substance wa; CITATION_NUMBERS=[]; DETAILS_JSON={"cas_number":"84041-77-0","citation":"","dose":"In a subchronic oral toxicity study, the NOAEL was set at 50 mg/kg bw/day, the NOEL at 5 mg/kg bw/day.","duration":"subchronic","effect":". Purity of the hair dye as well as the impurities in the test material(s) have not been fully characterised. Log Pow of the test material has not been reported. N,N’-bis-(2-hydroxyethyl)-2-nitro-p-phenylenediamine is a secondary amine, and thus, it is prone to nitrosation. No information is provided on the nitrosamine content in the test material. In a subchronic oral toxicity study, the NOAEL was set at 50 mg/kg bw/day, the NOEL at 5 mg/kg bw/day. The test substance elicited maternal toxicity at 1000 mg/kg, the NOAEL in this study was set at 100 mg/kg bw/day. The NOAEL of embryotoxicity and teratogenicity was set at 1000 mg/kg bw/day. A 1 % suspension of N,N’-bis-(2-hydroxyethyl)-2-nitro-p-phenylenediamine was neither irritating nor corrosive when applied to the rabbit skin under occlusive conditions. It was considered to be non-irritating to the eye. However, it cannot be excluded that N,N’-bis-(2- hydroxyethyl)-2-nitro-p-phenylenediamine has sensitization potential. The mean percutaneous absorption of the test substance wa","endpoint":"repeated dose toxicity","ingredient":"codes","loael_value":"","noael_unit":"mg/kg bw/day","noael_value":"100","page":18,"route":"oral","species":"rabbit","study_id":"out257_en_noael_007"}
UnifiedCodex:SCCNFP:beta.noael_studies	repeated dose toxicity	1000	mg/kg bw/day	rabbit	oral	subchronic	repeated dose toxicity	SOURCE_SUBDIR=out257_en; REPORT_TITLE=OPINION OF THE SCIENTIFIC COMMITTEE ON COSMETIC PRODUCTS AND NON-FOOD PRODUCTS INTENDED FOR CONSUMERS CONCERNING N,N’-BIS-(2-HYDROXYETHYL)-2-NITRO-P-PHENYLENEDIAMINE COLIPA n° B34; OPINION_NUMBER=SCCNFP/0781/04; COMMITTEE=SCCNFP; REPORT_DATE=adopted by the SCCNFP on 23 April 2004; VALUE_TEXT=1000; DOSE=In a subchronic oral toxicity study, the NOAEL was set at 50 mg/kg bw/day, the NOEL at 5 mg/kg bw/day.; EFFECT=the test material(s) have not been fully characterised. Log Pow of the test material has not been reported. N,N’-bis-(2-hydroxyethyl)-2-nitro-p-phenylenediamine is a secondary amine, and thus, it is prone to nitrosation. No information is provided on the nitrosamine content in the test material. In a subchronic oral toxicity study, the NOAEL was set at 50 mg/kg bw/day, the NOEL at 5 mg/kg bw/day. The test substance elicited maternal toxicity at 1000 mg/kg, the NOAEL in this study was set at 100 mg/kg bw/day. The NOAEL of embryotoxicity and teratogenicity was set at 1000 mg/kg bw/day. A 1 % suspension of N,N’-bis-(2-hydroxyethyl)-2-nitro-p-phenylenediamine was neither irritating nor corrosive when applied to the rabbit skin under occlusive conditions. It was considered to be non-irritating to the eye. However, it cannot be excluded that N,N’-bis-(2- hydroxyethyl)-2-nitro-p-phenylenediamine has sensitization potential. The mean percutaneous absorption of the test substance was 0.22% of applied 14C equivalent to 2.37 µg/cm2 test; CITATION_NUMBERS=[]; DETAILS_JSON={"cas_number":"84041-77-0","citation":"","dose":"In a subchronic oral toxicity study, the NOAEL was set at 50 mg/kg bw/day, the NOEL at 5 mg/kg bw/day.","duration":"subchronic","effect":"the test material(s) have not been fully characterised. Log Pow of the test material has not been reported. N,N’-bis-(2-hydroxyethyl)-2-nitro-p-phenylenediamine is a secondary amine, and thus, it is prone to nitrosation. No information is provided on the nitrosamine content in the test material. In a subchronic oral toxicity study, the NOAEL was set at 50 mg/kg bw/day, the NOEL at 5 mg/kg bw/day. The test substance elicited maternal toxicity at 1000 mg/kg, the NOAEL in this study was set at 100 mg/kg bw/day. The NOAEL of embryotoxicity and teratogenicity was set at 1000 mg/kg bw/day. A 1 % suspension of N,N’-bis-(2-hydroxyethyl)-2-nitro-p-phenylenediamine was neither irritating nor corrosive when applied to the rabbit skin under occlusive conditions. It was considered to be non-irritating to the eye. However, it cannot be excluded that N,N’-bis-(2- hydroxyethyl)-2-nitro-p-phenylenediamine has sensitization potential. The mean percutaneous absorption of the test substance was 0.22% of applied 14C equivalent to 2.37 µg/cm2 test","endpoint":"repeated dose toxicity","ingredient":"codes","loael_value":"","noael_unit":"mg/kg bw/day","noael_value":"1000","page":18,"route":"oral","species":"rabbit","study_id":"out257_en_noael_008"}

UnifiedCodex:SCCS_SHADOW:beta.noael_studies 38 endpoints

Source	Endpoint Type	Value	Unit	Species	Route	Duration	Study Type	Reference
UnifiedCodex:SCCS_SHADOW:beta.noael_studies	-	1200	mg/kg/day	human	-	-	-	SOURCE_SUBDIR=sccs_o_019; REPORT_TITLE=OPINION ON N,N'-bis-(2-Hydroxyethyl)-2-nitro-p-phenylenediamine COLIPA n° B34; OPINION_NUMBER=SCCS/1228/09; COMMITTEE=Scientific Committee on Consumer Safety (SCCS); REPORT_DATE=12 July 2010; VALUE_TEXT=1200; DOSE=cantly increase in the percentage of male foetuses noted in the low dose group was not considered to be of toxicological significance.; EFFECT=cantly increase in the percentage of male foetuses noted in the low dose group was not considered to be of toxicological significance. The number of small foetuses was comparable between groups. No relevance was attributed to the minor anomalies noted in one low dose foetus. Visceral examination did not show any dose related findings. No relevant foetal treatment- related skeletal changes were reported. Conclusion No maternal toxicity, foetal toxicity or teratogenicity was seen. On the basis of these results, the No Observed Adverse Effect Level (NOAEL) for N,N’-bis-(2-hydroxyethyl)-2- nitro-p-phenylenediamine should be considered to be 1200 mg/kg/day. Ref.: 12 3.3.9. Toxicokinetics No data submitted 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 3.3.13. Safety evaluation (including calculation of the MoS) CAL; CITATION=Ref.: 12 3; CITATION_NUMBERS=[12,3]; REFERENCE=Ref.: 12 3; DETAILS_JSON={"cas_number":"84041-77-0","citation":"Ref.: 12 3","dose":"cantly increase in the percentage of male foetuses noted in the low dose group was not considered to be of toxicological significance.","duration":"","effect":"cantly increase in the percentage of male foetuses noted in the low dose group was not considered to be of toxicological significance. The number of small foetuses was comparable between groups. No relevance was attributed to the minor anomalies noted in one low dose foetus. Visceral examination did not show any dose related findings. No relevant foetal treatment- related skeletal changes were reported. Conclusion No maternal toxicity, foetal toxicity or teratogenicity was seen. On the basis of these results, the No Observed Adverse Effect Level (NOAEL) for N,N’-bis-(2-hydroxyethyl)-2- nitro-p-phenylenediamine should be considered to be 1200 mg/kg/day. Ref.: 12 3.3.9. Toxicokinetics No data submitted 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 3.3.13. Safety evaluation (including calculation of the MoS) CAL","endpoint":"","ingredient":"N,N'-bis-(2-Hydroxyethyl)-2-nitro-p-phenylenediamine","loael_value":"","noael_unit":"mg/kg/day","noael_value":"1200","page":27,"route":"","species":"human","study_id":"sccs_o_019_noael_002"}
UnifiedCodex:SCCS_SHADOW:beta.noael_studies	-	1200	mg/kg/day	human	-	-	-	SOURCE_SUBDIR=sccs_o_019; REPORT_TITLE=OPINION ON N,N'-bis-(2-Hydroxyethyl)-2-nitro-p-phenylenediamine COLIPA n° B34; OPINION_NUMBER=SCCS/1228/09; COMMITTEE=Scientific Committee on Consumer Safety (SCCS); REPORT_DATE=12 July 2010; VALUE_TEXT=1200; DOSE=of male foetuses noted in the low dose group was not considered to be of toxicological significance.; EFFECT=of male foetuses noted in the low dose group was not considered to be of toxicological significance. The number of small foetuses was comparable between groups. No relevance was attributed to the minor anomalies noted in one low dose foetus. Visceral examination did not show any dose related findings. No relevant foetal treatment- related skeletal changes were reported. Conclusion No maternal toxicity, foetal toxicity or teratogenicity was seen. On the basis of these results, the No Observed Adverse Effect Level (NOAEL) for N,N’-bis-(2-hydroxyethyl)-2- nitro-p-phenylenediamine should be considered to be 1200 mg/kg/day. Ref.: 12 3.3.9. Toxicokinetics No data submitted 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 3.3.13. Safety evaluation (including calculation of the MoS) CALCULATIO; CITATION=Ref.: 12 3; CITATION_NUMBERS=[12,3]; REFERENCE=Ref.: 12 3; DETAILS_JSON={"cas_number":"84041-77-0","citation":"Ref.: 12 3","dose":"of male foetuses noted in the low dose group was not considered to be of toxicological significance.","duration":"","effect":"of male foetuses noted in the low dose group was not considered to be of toxicological significance. The number of small foetuses was comparable between groups. No relevance was attributed to the minor anomalies noted in one low dose foetus. Visceral examination did not show any dose related findings. No relevant foetal treatment- related skeletal changes were reported. Conclusion No maternal toxicity, foetal toxicity or teratogenicity was seen. On the basis of these results, the No Observed Adverse Effect Level (NOAEL) for N,N’-bis-(2-hydroxyethyl)-2- nitro-p-phenylenediamine should be considered to be 1200 mg/kg/day. Ref.: 12 3.3.9. Toxicokinetics No data submitted 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 3.3.13. Safety evaluation (including calculation of the MoS) CALCULATIO","endpoint":"","ingredient":"N,N'-bis-(2-Hydroxyethyl)-2-nitro-p-phenylenediamine","loael_value":"","noael_unit":"mg/kg/day","noael_value":"1200","page":27,"route":"","species":"human","study_id":"sccs_o_019_noael_003"}
UnifiedCodex:SCCS_SHADOW:beta.noael_studies	-	50	mg/kg bw/day	rat	-	4 weeks	-	SOURCE_SUBDIR=sccs_o_096; REPORT_TITLE=OPINION ON N,N'-bis-(2-Hydroxyethyl)-2-nitro-p-phenylenediamine COLIPA n° B34; OPINION_NUMBER=SCCS/1463/12; COMMITTEE=Scientific Committee on Consumer Safety (SCCS); REPORT_DATE=18 September 2012; VALUE_TEXT=50; DOSE=at week 6 in the middle and the high dose group and at week 13 in the high dose group only, calcium levels were increased in males and females at week 6 in the middle and the high dose group.; EFFECT=at week 6 in the middle and the high dose group and at week 13 in the high dose group only, calcium levels were increased in males and females at week 6 in the middle and the high dose group. Liver and kidney weights of males were increased in the high dose group. With the exception of inflammatory changes found in several organs in treated and control groups no relevant morphological changes were revealed. After the recovery period no differences in haematology, clinical chemistry and organ weights were seen. The NOAEL is 50 mg/kg bw/day, the NOEL 5 mg/kg bw/day. Ref.: 6 Comment The dose-spacing between the mid and high dose was very large. Guideline: OECD 408 (1998) Species/strain: rat, Wistar Hannover (HsdBrlHan:Wist) Group size: 120 (10 males and 10 females per group; control and high dose group: additional 5 males and 5 females for 4 weeks of recovery) Test substance: B034 Batch: DALA 013106 (SAT 040411) Purity: 99.5%; CITATION=Ref.: 6 Comment The dose-spacing between the mid and high dose was very large; CITATION_NUMBERS=[6]; REFERENCE=Ref.: 6 Comment The dose-spacing between the mid and high dose was very large; DETAILS_JSON={"cas_number":"84041-77-0","citation":"Ref.: 6 Comment The dose-spacing between the mid and high dose was very large","dose":"at week 6 in the middle and the high dose group and at week 13 in the high dose group only, calcium levels were increased in males and females at week 6 in the middle and the high dose group.","duration":"4 weeks","effect":"at week 6 in the middle and the high dose group and at week 13 in the high dose group only, calcium levels were increased in males and females at week 6 in the middle and the high dose group. Liver and kidney weights of males were increased in the high dose group. With the exception of inflammatory changes found in several organs in treated and control groups no relevant morphological changes were revealed. After the recovery period no differences in haematology, clinical chemistry and organ weights were seen. The NOAEL is 50 mg/kg bw/day, the NOEL 5 mg/kg bw/day. Ref.: 6 Comment The dose-spacing between the mid and high dose was very large. Guideline: OECD 408 (1998) Species/strain: rat, Wistar Hannover (HsdBrlHan:Wist) Group size: 120 (10 males and 10 females per group; control and high dose group: additional 5 males and 5 females for 4 weeks of recovery) Test substance: B034 Batch: DALA 013106 (SAT 040411) Purity: 99.5%","endpoint":"","ingredient":"N,N'-bis-(2-Hydroxyethyl)-2-nitro-p-phenylenediamine","loael_value":"","noael_unit":"mg/kg bw/day","noael_value":"50","page":15,"route":"","species":"rat","study_id":"sccs_o_096_noael_001"}
UnifiedCodex:SCCS_SHADOW:beta.noael_studies	-	5	mg/kg bw/day	rat	-	4 weeks	-	SOURCE_SUBDIR=sccs_o_096; REPORT_TITLE=OPINION ON N,N'-bis-(2-Hydroxyethyl)-2-nitro-p-phenylenediamine COLIPA n° B34; OPINION_NUMBER=SCCS/1463/12; COMMITTEE=Scientific Committee on Consumer Safety (SCCS); REPORT_DATE=18 September 2012; VALUE_TEXT=5; DOSE=e high dose group and at week 13 in the high dose group only, calcium levels were increased in males and females at week 6 in the middle and the high dose group.; EFFECT=e high dose group and at week 13 in the high dose group only, calcium levels were increased in males and females at week 6 in the middle and the high dose group. Liver and kidney weights of males were increased in the high dose group. With the exception of inflammatory changes found in several organs in treated and control groups no relevant morphological changes were revealed. After the recovery period no differences in haematology, clinical chemistry and organ weights were seen. The NOAEL is 50 mg/kg bw/day, the NOEL 5 mg/kg bw/day. Ref.: 6 Comment The dose-spacing between the mid and high dose was very large. Guideline: OECD 408 (1998) Species/strain: rat, Wistar Hannover (HsdBrlHan:Wist) Group size: 120 (10 males and 10 females per group; control and high dose group: additional 5 males and 5 females for 4 weeks of recovery) Test substance: B034 Batch: DALA 013106 (SAT 040411) Purity: 99.5%; CITATION=Ref.: 6 Comment The dose-spacing between the mid and high dose was very large; CITATION_NUMBERS=[6]; REFERENCE=Ref.: 6 Comment The dose-spacing between the mid and high dose was very large; DETAILS_JSON={"cas_number":"84041-77-0","citation":"Ref.: 6 Comment The dose-spacing between the mid and high dose was very large","dose":"e high dose group and at week 13 in the high dose group only, calcium levels were increased in males and females at week 6 in the middle and the high dose group.","duration":"4 weeks","effect":"e high dose group and at week 13 in the high dose group only, calcium levels were increased in males and females at week 6 in the middle and the high dose group. Liver and kidney weights of males were increased in the high dose group. With the exception of inflammatory changes found in several organs in treated and control groups no relevant morphological changes were revealed. After the recovery period no differences in haematology, clinical chemistry and organ weights were seen. The NOAEL is 50 mg/kg bw/day, the NOEL 5 mg/kg bw/day. Ref.: 6 Comment The dose-spacing between the mid and high dose was very large. Guideline: OECD 408 (1998) Species/strain: rat, Wistar Hannover (HsdBrlHan:Wist) Group size: 120 (10 males and 10 females per group; control and high dose group: additional 5 males and 5 females for 4 weeks of recovery) Test substance: B034 Batch: DALA 013106 (SAT 040411) Purity: 99.5%","endpoint":"","ingredient":"N,N'-bis-(2-Hydroxyethyl)-2-nitro-p-phenylenediamine","loael_value":"","noael_unit":"mg/kg bw/day","noael_value":"5","page":15,"route":"","species":"rat","study_id":"sccs_o_096_noael_002"}
UnifiedCodex:SCCS_SHADOW:beta.noael_studies	-	50	mg/kg bw/day	rat	-	4 weeks	-	SOURCE_SUBDIR=sccs_o_196; REPORT_TITLE=OPINION ON N,N'-Bis-(2-hydroxyethyl)-2-nitro-p-phenylenediamine (B34); OPINION_NUMBER=SCCS/1572/16; COMMITTEE=Scientific Committee on Consumer Safety (SCCS); REPORT_DATE=Final version of 16 September 2016; VALUE_TEXT=50; DOSE=week 6 in the middle- and the high-dose group and at week 13 in the high-dose group only, calcium levels were increased in males and females at week 6 in the middle and the high-dose group.; EFFECT=week 6 in the middle- and the high-dose group and at week 13 in the high-dose group only, calcium levels were increased in males and females at week 6 in the middle and the high-dose group. Liver and kidney weights of males were increased in the high-dose group. With the exception of inflammatory changes found in several organs in treated and control groups, no relevant morphological changes were revealed. After the recovery period, no differences in haematology, clinical chemistry and organ weights were seen. The NOAEL is 50 mg/kg bw/day, the NOEL 5 mg/kg bw/day. Ref.: 6, submission I Comment The dose-spacing between the mid and high dose was very large. Guideline: OECD 408 (1998) Species/strain: rat, Wistar Hannover (HsdBrlHan:Wist) Group size: 120 (10 males and 10 females per group; control and high dose group: additional 5 males and 5 females for 4 weeks of recovery) Test substance: B034 Batch: DALA 013106 (SAT 040411) Purity: 99.5% Vehicle: 0.5% aqueous carboxymethylcellulose Dose levels: 0, 80, 240 and 720 mg/kg bw Stab; CITATION=Ref.: 6, submission I Comment The dose-spacing between the mid and high dose was very large; CITATION_NUMBERS=[6]; REFERENCE=Ref.: 6, submission I Comment The dose-spacing between the mid and high dose was very large; DETAILS_JSON={"cas_number":"84041-77-0","citation":"Ref.: 6, submission I Comment The dose-spacing between the mid and high dose was very large","dose":"week 6 in the middle- and the high-dose group and at week 13 in the high-dose group only, calcium levels were increased in males and females at week 6 in the middle and the high-dose group.","duration":"4 weeks","effect":"week 6 in the middle- and the high-dose group and at week 13 in the high-dose group only, calcium levels were increased in males and females at week 6 in the middle and the high-dose group. Liver and kidney weights of males were increased in the high-dose group. With the exception of inflammatory changes found in several organs in treated and control groups, no relevant morphological changes were revealed. After the recovery period, no differences in haematology, clinical chemistry and organ weights were seen. The NOAEL is 50 mg/kg bw/day, the NOEL 5 mg/kg bw/day. Ref.: 6, submission I Comment The dose-spacing between the mid and high dose was very large. Guideline: OECD 408 (1998) Species/strain: rat, Wistar Hannover (HsdBrlHan:Wist) Group size: 120 (10 males and 10 females per group; control and high dose group: additional 5 males and 5 females for 4 weeks of recovery) Test substance: B034 Batch: DALA 013106 (SAT 040411) Purity: 99.5% Vehicle: 0.5% aqueous carboxymethylcellulose Dose levels: 0, 80, 240 and 720 mg/kg bw Stab","endpoint":"","ingredient":"N,N'-bis-(2-Hydroxyethyl)-2-nitro-p-phenylenediamine","loael_value":"","noael_unit":"mg/kg bw/day","noael_value":"50","page":14,"route":"","species":"rat","study_id":"sccs_o_196_noael_001"}
UnifiedCodex:SCCS_SHADOW:beta.noael_studies	-	5	mg/kg bw/day	rat	-	4 weeks	-	SOURCE_SUBDIR=sccs_o_196; REPORT_TITLE=OPINION ON N,N'-Bis-(2-hydroxyethyl)-2-nitro-p-phenylenediamine (B34); OPINION_NUMBER=SCCS/1572/16; COMMITTEE=Scientific Committee on Consumer Safety (SCCS); REPORT_DATE=Final version of 16 September 2016; VALUE_TEXT=5; DOSE=high-dose group and at week 13 in the high-dose group only, calcium levels were increased in males and females at week 6 in the middle and the high-dose group.; EFFECT=high-dose group and at week 13 in the high-dose group only, calcium levels were increased in males and females at week 6 in the middle and the high-dose group. Liver and kidney weights of males were increased in the high-dose group. With the exception of inflammatory changes found in several organs in treated and control groups, no relevant morphological changes were revealed. After the recovery period, no differences in haematology, clinical chemistry and organ weights were seen. The NOAEL is 50 mg/kg bw/day, the NOEL 5 mg/kg bw/day. Ref.: 6, submission I Comment The dose-spacing between the mid and high dose was very large. Guideline: OECD 408 (1998) Species/strain: rat, Wistar Hannover (HsdBrlHan:Wist) Group size: 120 (10 males and 10 females per group; control and high dose group: additional 5 males and 5 females for 4 weeks of recovery) Test substance: B034 Batch: DALA 013106 (SAT 040411) Purity: 99.5% Vehicle: 0.5% aqueous carboxymethylcellulose Dose levels: 0, 80, 240 and 720 mg/kg bw Stability: > 6 hours at room temp; CITATION=Ref.: 6, submission I Comment The dose-spacing between the mid and high dose was very large; CITATION_NUMBERS=[6]; REFERENCE=Ref.: 6, submission I Comment The dose-spacing between the mid and high dose was very large; DETAILS_JSON={"cas_number":"84041-77-0","citation":"Ref.: 6, submission I Comment The dose-spacing between the mid and high dose was very large","dose":"high-dose group and at week 13 in the high-dose group only, calcium levels were increased in males and females at week 6 in the middle and the high-dose group.","duration":"4 weeks","effect":"high-dose group and at week 13 in the high-dose group only, calcium levels were increased in males and females at week 6 in the middle and the high-dose group. Liver and kidney weights of males were increased in the high-dose group. With the exception of inflammatory changes found in several organs in treated and control groups, no relevant morphological changes were revealed. After the recovery period, no differences in haematology, clinical chemistry and organ weights were seen. The NOAEL is 50 mg/kg bw/day, the NOEL 5 mg/kg bw/day. Ref.: 6, submission I Comment The dose-spacing between the mid and high dose was very large. Guideline: OECD 408 (1998) Species/strain: rat, Wistar Hannover (HsdBrlHan:Wist) Group size: 120 (10 males and 10 females per group; control and high dose group: additional 5 males and 5 females for 4 weeks of recovery) Test substance: B034 Batch: DALA 013106 (SAT 040411) Purity: 99.5% Vehicle: 0.5% aqueous carboxymethylcellulose Dose levels: 0, 80, 240 and 720 mg/kg bw Stability: > 6 hours at room temp","endpoint":"","ingredient":"N,N'-bis-(2-Hydroxyethyl)-2-nitro-p-phenylenediamine","loael_value":"","noael_unit":"mg/kg bw/day","noael_value":"5","page":14,"route":"","species":"rat","study_id":"sccs_o_196_noael_002"}
UnifiedCodex:SCCS_SHADOW:beta.noael_studies	-	240	mg/kg/day	-	-	-	-	SOURCE_SUBDIR=sccs_o_196; REPORT_TITLE=OPINION ON N,N'-Bis-(2-hydroxyethyl)-2-nitro-p-phenylenediamine (B34); OPINION_NUMBER=SCCS/1572/16; COMMITTEE=Scientific Committee on Consumer Safety (SCCS); REPORT_DATE=Final version of 16 September 2016; VALUE_TEXT=240; DOSE=By the end of the recovery period, the distribution of these deposits was multi-focal in the treated animals and focal in the controls.; EFFECT=ose- related increase in the incidence of yellow-brown, intra-cytoplasmic pigmentation. These deposits were not evaluated as an adverse effect, since no toxicologically significant differences were observed in the accumulation of pigment deposits. By the end of the recovery period, the distribution of these deposits was multi-focal in the treated animals and focal in the controls. No other organ was affected by treatment. Conclusion On the basis of these results, the mid-dose (240 mg/kg/day) may be considered the No Observed Adverse Effect Level (NOAEL) for N,N’-bis-(2-hydroxyethyl)-2-nitro-p- phenylenediamine. Ref.: 11, submission II Comment The NOAEL of 240 mg/kg bw/d could be used for the calculation of the Margin of Safety (MoS).; CITATION=Ref.: 11, submission II Comment The NOAEL of 240 mg/kg bw/d could be used for the calculation of the Margin of Safety (MoS); CITATION_NUMBERS=[11,240]; REFERENCE=Ref.: 11, submission II Comment The NOAEL of 240 mg/kg bw/d could be used for the calculation of the Margin of Safety (MoS); DETAILS_JSON={"cas_number":"84041-77-0","citation":"Ref.: 11, submission II Comment The NOAEL of 240 mg/kg bw/d could be used for the calculation of the Margin of Safety (MoS)","dose":"By the end of the recovery period, the distribution of these deposits was multi-focal in the treated animals and focal in the controls.","duration":"","effect":"ose- related increase in the incidence of yellow-brown, intra-cytoplasmic pigmentation. These deposits were not evaluated as an adverse effect, since no toxicologically significant differences were observed in the accumulation of pigment deposits. By the end of the recovery period, the distribution of these deposits was multi-focal in the treated animals and focal in the controls. No other organ was affected by treatment. Conclusion On the basis of these results, the mid-dose (240 mg/kg/day) may be considered the No Observed Adverse Effect Level (NOAEL) for N,N’-bis-(2-hydroxyethyl)-2-nitro-p- phenylenediamine. Ref.: 11, submission II Comment The NOAEL of 240 mg/kg bw/d could be used for the calculation of the Margin of Safety (MoS).","endpoint":"","ingredient":"N,N'-bis-(2-Hydroxyethyl)-2-nitro-p-phenylenediamine","loael_value":"","noael_unit":"mg/kg/day","noael_value":"240","page":15,"route":"","species":"","study_id":"sccs_o_196_noael_003"}
UnifiedCodex:SCCS_SHADOW:beta.noael_studies	-	240	mg/kg/day	-	-	-	-	SOURCE_SUBDIR=sccs_o_196; REPORT_TITLE=OPINION ON N,N'-Bis-(2-hydroxyethyl)-2-nitro-p-phenylenediamine (B34); OPINION_NUMBER=SCCS/1572/16; COMMITTEE=Scientific Committee on Consumer Safety (SCCS); REPORT_DATE=Final version of 16 September 2016; VALUE_TEXT=240; DOSE=By the end of the recovery period, the distribution of these deposits was multi-focal in the treated animals and focal in the controls.; EFFECT=ence of yellow-brown, intra-cytoplasmic pigmentation. These deposits were not evaluated as an adverse effect, since no toxicologically significant differences were observed in the accumulation of pigment deposits. By the end of the recovery period, the distribution of these deposits was multi-focal in the treated animals and focal in the controls. No other organ was affected by treatment. Conclusion On the basis of these results, the mid-dose (240 mg/kg/day) may be considered the No Observed Adverse Effect Level (NOAEL) for N,N’-bis-(2-hydroxyethyl)-2-nitro-p- phenylenediamine. Ref.: 11, submission II Comment The NOAEL of 240 mg/kg bw/d could be used for the calculation of the Margin of Safety (MoS).; CITATION=Ref.: 11, submission II Comment The NOAEL of 240 mg/kg bw/d could be used for the calculation of the Margin of Safety (MoS); CITATION_NUMBERS=[11,240]; REFERENCE=Ref.: 11, submission II Comment The NOAEL of 240 mg/kg bw/d could be used for the calculation of the Margin of Safety (MoS); DETAILS_JSON={"cas_number":"84041-77-0","citation":"Ref.: 11, submission II Comment The NOAEL of 240 mg/kg bw/d could be used for the calculation of the Margin of Safety (MoS)","dose":"By the end of the recovery period, the distribution of these deposits was multi-focal in the treated animals and focal in the controls.","duration":"","effect":"ence of yellow-brown, intra-cytoplasmic pigmentation. These deposits were not evaluated as an adverse effect, since no toxicologically significant differences were observed in the accumulation of pigment deposits. By the end of the recovery period, the distribution of these deposits was multi-focal in the treated animals and focal in the controls. No other organ was affected by treatment. Conclusion On the basis of these results, the mid-dose (240 mg/kg/day) may be considered the No Observed Adverse Effect Level (NOAEL) for N,N’-bis-(2-hydroxyethyl)-2-nitro-p- phenylenediamine. Ref.: 11, submission II Comment The NOAEL of 240 mg/kg bw/d could be used for the calculation of the Margin of Safety (MoS).","endpoint":"","ingredient":"N,N'-bis-(2-Hydroxyethyl)-2-nitro-p-phenylenediamine","loael_value":"","noael_unit":"mg/kg/day","noael_value":"240","page":15,"route":"","species":"","study_id":"sccs_o_196_noael_004"}
UnifiedCodex:SCCS_SHADOW:beta.noael_studies	-	240	mg/kg bw/d	-	-	-	-	SOURCE_SUBDIR=sccs_o_196; REPORT_TITLE=OPINION ON N,N'-Bis-(2-hydroxyethyl)-2-nitro-p-phenylenediamine (B34); OPINION_NUMBER=SCCS/1572/16; COMMITTEE=Scientific Committee on Consumer Safety (SCCS); REPORT_DATE=Final version of 16 September 2016; VALUE_TEXT=240; DOSE=By the end of the recovery period, the distribution of these deposits was multi-focal in the treated animals and focal in the controls.; EFFECT=fect, since no toxicologically significant differences were observed in the accumulation of pigment deposits. By the end of the recovery period, the distribution of these deposits was multi-focal in the treated animals and focal in the controls. No other organ was affected by treatment. Conclusion On the basis of these results, the mid-dose (240 mg/kg/day) may be considered the No Observed Adverse Effect Level (NOAEL) for N,N’-bis-(2-hydroxyethyl)-2-nitro-p- phenylenediamine. Ref.: 11, submission II Comment The NOAEL of 240 mg/kg bw/d could be used for the calculation of the Margin of Safety (MoS).; CITATION=Ref.: 11, submission II Comment The NOAEL of 240 mg/kg bw/d could be used for the calculation of the Margin of Safety (MoS); CITATION_NUMBERS=[11,240]; REFERENCE=Ref.: 11, submission II Comment The NOAEL of 240 mg/kg bw/d could be used for the calculation of the Margin of Safety (MoS); DETAILS_JSON={"cas_number":"84041-77-0","citation":"Ref.: 11, submission II Comment The NOAEL of 240 mg/kg bw/d could be used for the calculation of the Margin of Safety (MoS)","dose":"By the end of the recovery period, the distribution of these deposits was multi-focal in the treated animals and focal in the controls.","duration":"","effect":"fect, since no toxicologically significant differences were observed in the accumulation of pigment deposits. By the end of the recovery period, the distribution of these deposits was multi-focal in the treated animals and focal in the controls. No other organ was affected by treatment. Conclusion On the basis of these results, the mid-dose (240 mg/kg/day) may be considered the No Observed Adverse Effect Level (NOAEL) for N,N’-bis-(2-hydroxyethyl)-2-nitro-p- phenylenediamine. Ref.: 11, submission II Comment The NOAEL of 240 mg/kg bw/d could be used for the calculation of the Margin of Safety (MoS).","endpoint":"","ingredient":"N,N'-bis-(2-Hydroxyethyl)-2-nitro-p-phenylenediamine","loael_value":"","noael_unit":"mg/kg bw/d","noael_value":"240","page":15,"route":"","species":"","study_id":"sccs_o_196_noael_005"}
UnifiedCodex:SCCS_SHADOW:beta.noael_studies	dermal absorption	1200	mg/kg/day	rat	dermal	-	dermal absorption	SOURCE_SUBDIR=sccs_o_096; REPORT_TITLE=OPINION ON N,N'-bis-(2-Hydroxyethyl)-2-nitro-p-phenylenediamine COLIPA n° B34; OPINION_NUMBER=SCCS/1463/12; COMMITTEE=Scientific Committee on Consumer Safety (SCCS); REPORT_DATE=18 September 2012; VALUE_TEXT=1200; DOSE=cantly increase in the percentage of male foetuses noted in the low dose group was not considered to be of toxicological significance.; EFFECT=cantly increase in the percentage of male foetuses noted in the low dose group was not considered to be of toxicological significance. The number of small foetuses was comparable between groups. No relevance was attributed to the minor anomalies noted in one low dose foetus. Visceral examination did not show any dose related findings. No relevant foetal treatment- related skeletal changes were reported. Conclusion No maternal toxicity, foetal toxicity or teratogenicity was seen. On the basis of these results, the No Observed Adverse Effect Level (NOAEL) for N,N’-bis-(2-hydroxyethyl)-2- nitro-p-phenylenediamine should be considered to be 1200 mg/kg/day. Ref.: 12 3.3.9. Toxicokinetics Taken from SCCNFP/0781/04 Percutaneous penetration / dermal absorption of a hair dye formulation in rats Guideline: / Animal strain: Sprague Dawley rats (Him:OFA) 5 males and 5 females in each of 2 experiments Method: 14C ring labelled N,N’-bis-(2-hydroxyethyl)-2-nitro-p-phenylenediamine in a hair dye formulation (without developer), radiochemical purity > 98%, applied to; CITATION=Ref.: 12 3; CITATION_NUMBERS=[12,3]; REFERENCE=Ref.: 12 3; DETAILS_JSON={"cas_number":"84041-77-0","citation":"Ref.: 12 3","dose":"cantly increase in the percentage of male foetuses noted in the low dose group was not considered to be of toxicological significance.","duration":"","effect":"cantly increase in the percentage of male foetuses noted in the low dose group was not considered to be of toxicological significance. The number of small foetuses was comparable between groups. No relevance was attributed to the minor anomalies noted in one low dose foetus. Visceral examination did not show any dose related findings. No relevant foetal treatment- related skeletal changes were reported. Conclusion No maternal toxicity, foetal toxicity or teratogenicity was seen. On the basis of these results, the No Observed Adverse Effect Level (NOAEL) for N,N’-bis-(2-hydroxyethyl)-2- nitro-p-phenylenediamine should be considered to be 1200 mg/kg/day. Ref.: 12 3.3.9. Toxicokinetics Taken from SCCNFP/0781/04 Percutaneous penetration / dermal absorption of a hair dye formulation in rats Guideline: / Animal strain: Sprague Dawley rats (Him:OFA) 5 males and 5 females in each of 2 experiments Method: 14C ring labelled N,N’-bis-(2-hydroxyethyl)-2-nitro-p-phenylenediamine in a hair dye formulation (without developer), radiochemical purity > 98%, applied to","endpoint":"dermal absorption","ingredient":"N,N'-bis-(2-Hydroxyethyl)-2-nitro-p-phenylenediamine","loael_value":"","noael_unit":"mg/kg/day","noael_value":"1200","page":33,"route":"dermal","species":"rat","study_id":"sccs_o_096_noael_008"}
UnifiedCodex:SCCS_SHADOW:beta.noael_studies	dermal absorption	1200	mg/kg/day	rat	dermal	-	dermal absorption	SOURCE_SUBDIR=sccs_o_096; REPORT_TITLE=OPINION ON N,N'-bis-(2-Hydroxyethyl)-2-nitro-p-phenylenediamine COLIPA n° B34; OPINION_NUMBER=SCCS/1463/12; COMMITTEE=Scientific Committee on Consumer Safety (SCCS); REPORT_DATE=18 September 2012; VALUE_TEXT=1200; DOSE=of male foetuses noted in the low dose group was not considered to be of toxicological significance.; EFFECT=of male foetuses noted in the low dose group was not considered to be of toxicological significance. The number of small foetuses was comparable between groups. No relevance was attributed to the minor anomalies noted in one low dose foetus. Visceral examination did not show any dose related findings. No relevant foetal treatment- related skeletal changes were reported. Conclusion No maternal toxicity, foetal toxicity or teratogenicity was seen. On the basis of these results, the No Observed Adverse Effect Level (NOAEL) for N,N’-bis-(2-hydroxyethyl)-2- nitro-p-phenylenediamine should be considered to be 1200 mg/kg/day. Ref.: 12 3.3.9. Toxicokinetics Taken from SCCNFP/0781/04 Percutaneous penetration / dermal absorption of a hair dye formulation in rats Guideline: / Animal strain: Sprague Dawley rats (Him:OFA) 5 males and 5 females in each of 2 experiments Method: 14C ring labelled N,N’-bis-(2-hydroxyethyl)-2-nitro-p-phenylenediamine in a hair dye formulation (without developer), radiochemical purity > 98%, applied to the bac; CITATION=Ref.: 12 3; CITATION_NUMBERS=[12,3]; REFERENCE=Ref.: 12 3; DETAILS_JSON={"cas_number":"84041-77-0","citation":"Ref.: 12 3","dose":"of male foetuses noted in the low dose group was not considered to be of toxicological significance.","duration":"","effect":"of male foetuses noted in the low dose group was not considered to be of toxicological significance. The number of small foetuses was comparable between groups. No relevance was attributed to the minor anomalies noted in one low dose foetus. Visceral examination did not show any dose related findings. No relevant foetal treatment- related skeletal changes were reported. Conclusion No maternal toxicity, foetal toxicity or teratogenicity was seen. On the basis of these results, the No Observed Adverse Effect Level (NOAEL) for N,N’-bis-(2-hydroxyethyl)-2- nitro-p-phenylenediamine should be considered to be 1200 mg/kg/day. Ref.: 12 3.3.9. Toxicokinetics Taken from SCCNFP/0781/04 Percutaneous penetration / dermal absorption of a hair dye formulation in rats Guideline: / Animal strain: Sprague Dawley rats (Him:OFA) 5 males and 5 females in each of 2 experiments Method: 14C ring labelled N,N’-bis-(2-hydroxyethyl)-2-nitro-p-phenylenediamine in a hair dye formulation (without developer), radiochemical purity > 98%, applied to the bac","endpoint":"dermal absorption","ingredient":"N,N'-bis-(2-Hydroxyethyl)-2-nitro-p-phenylenediamine","loael_value":"","noael_unit":"mg/kg/day","noael_value":"1200","page":33,"route":"dermal","species":"rat","study_id":"sccs_o_096_noael_009"}
UnifiedCodex:SCCS_SHADOW:beta.noael_studies	dermal absorption	1200	mg/kg/day	rat	dermal	-	dermal absorption	SOURCE_SUBDIR=sccs_o_196; REPORT_TITLE=OPINION ON N,N'-Bis-(2-hydroxyethyl)-2-nitro-p-phenylenediamine (B34); OPINION_NUMBER=SCCS/1572/16; COMMITTEE=Scientific Committee on Consumer Safety (SCCS); REPORT_DATE=Final version of 16 September 2016; VALUE_TEXT=1200; DOSE=ficant increase in the percentage of male foetuses noted in the low-dose group was not considered to be of toxicological significance.; EFFECT=SCCS-rejected applicant NOAEL: ficant increase in the percentage of male foetuses noted in the low-dose group was not considered to be of toxicological significance. The number of small foetuses was comparable between groups. No relevance was attributed to the minor anomalies noted in one low dose foetus. Visceral examination did not show any dose-related findings. No relevant foetal treatment- related skeletal changes were reported. Conclusion No maternal toxicity, foetal toxicity or teratogenicity was seen. On the basis of these results, the No Observed Adverse Effect Level (NOAEL) for N,N’-bis-(2-hydroxyethyl)-2- nitro-p-phenylenediamine should be considered to be 1200 mg/kg/day. Ref.: 12, submission II 3.3.9 Toxicokinetics No new data submitted. 3.3.9.1 Toxicokinetics in laboratory animals Taken from SCCNFP/0781/04 Percutaneous penetration / dermal absorption of a hair dye formulation in rats Guideline: / Animal strain: Sprague Dawley rats (Him:OFA) 5 males and 5 females in each of 2 experiments Method: 14C ring labelled N,N’-bis-(2-hydroxyethyl)-2-nitro-p-phenylenediamine i; CITATION=Ref.: 12, submission II 3; CITATION_NUMBERS=[12,3]; REFERENCE=Ref.: 12, submission II 3; DETAILS_JSON={"cas_number":"84041-77-0","citation":"Ref.: 12, submission II 3","dose":"ficant increase in the percentage of male foetuses noted in the low-dose group was not considered to be of toxicological significance.","duration":"","effect":"SCCS-rejected applicant NOAEL: ficant increase in the percentage of male foetuses noted in the low-dose group was not considered to be of toxicological significance. The number of small foetuses was comparable between groups. No relevance was attributed to the minor anomalies noted in one low dose foetus. Visceral examination did not show any dose-related findings. No relevant foetal treatment- related skeletal changes were reported. Conclusion No maternal toxicity, foetal toxicity or teratogenicity was seen. On the basis of these results, the No Observed Adverse Effect Level (NOAEL) for N,N’-bis-(2-hydroxyethyl)-2- nitro-p-phenylenediamine should be considered to be 1200 mg/kg/day. Ref.: 12, submission II 3.3.9 Toxicokinetics No new data submitted. 3.3.9.1 Toxicokinetics in laboratory animals Taken from SCCNFP/0781/04 Percutaneous penetration / dermal absorption of a hair dye formulation in rats Guideline: / Animal strain: Sprague Dawley rats (Him:OFA) 5 males and 5 females in each of 2 experiments Method: 14C ring labelled N,N’-bis-(2-hydroxyethyl)-2-nitro-p-phenylenediamine i","endpoint":"dermal absorption","ingredient":"N,N'-bis-(2-Hydroxyethyl)-2-nitro-p-phenylenediamine","loael_value":"","noael_unit":"mg/kg/day","noael_value":"1200","page":34,"route":"dermal","species":"rat","study_id":"sccs_o_196_noael_008"}
UnifiedCodex:SCCS_SHADOW:beta.noael_studies	dermal absorption	1200	mg/kg/day	rat	dermal	-	dermal absorption	SOURCE_SUBDIR=sccs_o_196; REPORT_TITLE=OPINION ON N,N'-Bis-(2-hydroxyethyl)-2-nitro-p-phenylenediamine (B34); OPINION_NUMBER=SCCS/1572/16; COMMITTEE=Scientific Committee on Consumer Safety (SCCS); REPORT_DATE=Final version of 16 September 2016; VALUE_TEXT=1200; DOSE=of male foetuses noted in the low-dose group was not considered to be of toxicological significance.; EFFECT=SCCS-rejected applicant NOAEL: of male foetuses noted in the low-dose group was not considered to be of toxicological significance. The number of small foetuses was comparable between groups. No relevance was attributed to the minor anomalies noted in one low dose foetus. Visceral examination did not show any dose-related findings. No relevant foetal treatment- related skeletal changes were reported. Conclusion No maternal toxicity, foetal toxicity or teratogenicity was seen. On the basis of these results, the No Observed Adverse Effect Level (NOAEL) for N,N’-bis-(2-hydroxyethyl)-2- nitro-p-phenylenediamine should be considered to be 1200 mg/kg/day. Ref.: 12, submission II 3.3.9 Toxicokinetics No new data submitted. 3.3.9.1 Toxicokinetics in laboratory animals Taken from SCCNFP/0781/04 Percutaneous penetration / dermal absorption of a hair dye formulation in rats Guideline: / Animal strain: Sprague Dawley rats (Him:OFA) 5 males and 5 females in each of 2 experiments Method: 14C ring labelled N,N’-bis-(2-hydroxyethyl)-2-nitro-p-phenylenediamine in a hai; CITATION=Ref.: 12, submission II 3; CITATION_NUMBERS=[12,3]; REFERENCE=Ref.: 12, submission II 3; DETAILS_JSON={"cas_number":"84041-77-0","citation":"Ref.: 12, submission II 3","dose":"of male foetuses noted in the low-dose group was not considered to be of toxicological significance.","duration":"","effect":"SCCS-rejected applicant NOAEL: of male foetuses noted in the low-dose group was not considered to be of toxicological significance. The number of small foetuses was comparable between groups. No relevance was attributed to the minor anomalies noted in one low dose foetus. Visceral examination did not show any dose-related findings. No relevant foetal treatment- related skeletal changes were reported. Conclusion No maternal toxicity, foetal toxicity or teratogenicity was seen. On the basis of these results, the No Observed Adverse Effect Level (NOAEL) for N,N’-bis-(2-hydroxyethyl)-2- nitro-p-phenylenediamine should be considered to be 1200 mg/kg/day. Ref.: 12, submission II 3.3.9 Toxicokinetics No new data submitted. 3.3.9.1 Toxicokinetics in laboratory animals Taken from SCCNFP/0781/04 Percutaneous penetration / dermal absorption of a hair dye formulation in rats Guideline: / Animal strain: Sprague Dawley rats (Him:OFA) 5 males and 5 females in each of 2 experiments Method: 14C ring labelled N,N’-bis-(2-hydroxyethyl)-2-nitro-p-phenylenediamine in a hai","endpoint":"dermal absorption","ingredient":"N,N'-bis-(2-Hydroxyethyl)-2-nitro-p-phenylenediamine","loael_value":"","noael_unit":"mg/kg/day","noael_value":"1200","page":34,"route":"dermal","species":"rat","study_id":"sccs_o_196_noael_009"}
UnifiedCodex:SCCS_SHADOW:beta.noael_studies	dermal absorption	=0.017	mg/kg bw/d	rat	oral	90-day	dermal absorption	SOURCE_SUBDIR=sccs_o_196; REPORT_TITLE=OPINION ON N,N'-Bis-(2-hydroxyethyl)-2-nitro-p-phenylenediamine (B34); OPINION_NUMBER=SCCS/1572/16; COMMITTEE=Scientific Committee on Consumer Safety (SCCS); REPORT_DATE=Final version of 16 September 2016; VALUE_TEXT== 0.017; DOSE=___________________________________________________________________________ 36 No data submitted 3.3.12 Special investigations 3.3.13 Safety evaluation (including calculation of the MoS) CALCULATION OF THE MARGIN OF SAFETY (Oxidative conditions) (on head concentration 1%) Absorption through the skin A = 1.76 µg/cm² Skin Area surface SAS = 580 cm...; EFFECT=___________________________________________________________________________ 36 No data submitted 3.3.12 Special investigations 3.3.13 Safety evaluation (including calculation of the MoS) CALCULATION OF THE MARGIN OF SAFETY (Oxidative conditions) (on head concentration 1%) Absorption through the skin A = 1.76 µg/cm² Skin Area surface SAS = 580 cm2 Dermal absorption per treatment SAS x A x 0.001 = 1.021 mg Typical body weight of human = 60 kg Systemic exposure dose (SED) SAS x A x 0.001/60 = 0.017 mg/kg bw/d No observed adverse effect level NOAEL = 240 mg/kg bw/d (90-day, oral, rat) Bioavailability 50%* = 120 mg/kg bw/d Margin of Safety adjusted NOAEL/SED = 7100 * standard procedure according to the SCCS's Notes of Guidance for the testing of cosmetic ingredients and their safety evaluation. (Non-oxidative conditions) (on head concentration 1.5%) Absorption through the skin A = 2.97 µg/cm² Skin Area surface SAS = 580 cm2 Dermal absorption per treatment SAS x A x 0.001 = 1.723 mg Typical body weight of human = 60 kg Systemic exposure dose (SED); CITATION_NUMBERS=[]; DETAILS_JSON={"cas_number":"84041-77-0","citation":"","dose":"___________________________________________________________________________ 36 No data submitted 3.3.12 Special investigations 3.3.13 Safety evaluation (including calculation of the MoS) CALCULATION OF THE MARGIN OF SAFETY (Oxidative conditions) (on head concentration 1%) Absorption through the skin A = 1.76 µg/cm² Skin Area surface SAS = 580 cm...","duration":"90-day","effect":"___________________________________________________________________________ 36 No data submitted 3.3.12 Special investigations 3.3.13 Safety evaluation (including calculation of the MoS) CALCULATION OF THE MARGIN OF SAFETY (Oxidative conditions) (on head concentration 1%) Absorption through the skin A = 1.76 µg/cm² Skin Area surface SAS = 580 cm2 Dermal absorption per treatment SAS x A x 0.001 = 1.021 mg Typical body weight of human = 60 kg Systemic exposure dose (SED) SAS x A x 0.001/60 = 0.017 mg/kg bw/d No observed adverse effect level NOAEL = 240 mg/kg bw/d (90-day, oral, rat) Bioavailability 50%* = 120 mg/kg bw/d Margin of Safety adjusted NOAEL/SED = 7100 * standard procedure according to the SCCS's Notes of Guidance for the testing of cosmetic ingredients and their safety evaluation. (Non-oxidative conditions) (on head concentration 1.5%) Absorption through the skin A = 2.97 µg/cm² Skin Area surface SAS = 580 cm2 Dermal absorption per treatment SAS x A x 0.001 = 1.723 mg Typical body weight of human = 60 kg Systemic exposure dose (SED)","endpoint":"dermal absorption","ingredient":"N,N'-bis-(2-Hydroxyethyl)-2-nitro-p-phenylenediamine","loael_value":"","noael_unit":"mg/kg bw/d","noael_value":"= 0.017","page":36,"route":"oral","species":"rat","study_id":"sccs_o_196_noael_010"}
UnifiedCodex:SCCS_SHADOW:beta.noael_studies	dermal absorption	=240	mg/kg bw/d	rat	oral	90-day	dermal absorption	SOURCE_SUBDIR=sccs_o_196; REPORT_TITLE=OPINION ON N,N'-Bis-(2-hydroxyethyl)-2-nitro-p-phenylenediamine (B34); OPINION_NUMBER=SCCS/1572/16; COMMITTEE=Scientific Committee on Consumer Safety (SCCS); REPORT_DATE=Final version of 16 September 2016; VALUE_TEXT== 240; DOSE=__________________________________________ 36 No data submitted 3.3.12 Special investigations 3.3.13 Safety evaluation (including calculation of the MoS) CALCULATION OF THE MARGIN OF SAFETY (Oxidative conditions) (on head concentration 1%) Absorption through the skin A = 1.76 µg/cm² Skin Area surface SAS = 580 cm2 Dermal absorption per treatment...; EFFECT=__________________________________________ 36 No data submitted 3.3.12 Special investigations 3.3.13 Safety evaluation (including calculation of the MoS) CALCULATION OF THE MARGIN OF SAFETY (Oxidative conditions) (on head concentration 1%) Absorption through the skin A = 1.76 µg/cm² Skin Area surface SAS = 580 cm2 Dermal absorption per treatment SAS x A x 0.001 = 1.021 mg Typical body weight of human = 60 kg Systemic exposure dose (SED) SAS x A x 0.001/60 = 0.017 mg/kg bw/d No observed adverse effect level NOAEL = 240 mg/kg bw/d (90-day, oral, rat) Bioavailability 50%* = 120 mg/kg bw/d Margin of Safety adjusted NOAEL/SED = 7100 * standard procedure according to the SCCS's Notes of Guidance for the testing of cosmetic ingredients and their safety evaluation. (Non-oxidative conditions) (on head concentration 1.5%) Absorption through the skin A = 2.97 µg/cm² Skin Area surface SAS = 580 cm2 Dermal absorption per treatment SAS x A x 0.001 = 1.723 mg Typical body weight of human = 60 kg Systemic exposure dose (SED) SAS x; CITATION_NUMBERS=[]; DETAILS_JSON={"cas_number":"84041-77-0","citation":"","dose":"__________________________________________ 36 No data submitted 3.3.12 Special investigations 3.3.13 Safety evaluation (including calculation of the MoS) CALCULATION OF THE MARGIN OF SAFETY (Oxidative conditions) (on head concentration 1%) Absorption through the skin A = 1.76 µg/cm² Skin Area surface SAS = 580 cm2 Dermal absorption per treatment...","duration":"90-day","effect":"__________________________________________ 36 No data submitted 3.3.12 Special investigations 3.3.13 Safety evaluation (including calculation of the MoS) CALCULATION OF THE MARGIN OF SAFETY (Oxidative conditions) (on head concentration 1%) Absorption through the skin A = 1.76 µg/cm² Skin Area surface SAS = 580 cm2 Dermal absorption per treatment SAS x A x 0.001 = 1.021 mg Typical body weight of human = 60 kg Systemic exposure dose (SED) SAS x A x 0.001/60 = 0.017 mg/kg bw/d No observed adverse effect level NOAEL = 240 mg/kg bw/d (90-day, oral, rat) Bioavailability 50%* = 120 mg/kg bw/d Margin of Safety adjusted NOAEL/SED = 7100 * standard procedure according to the SCCS's Notes of Guidance for the testing of cosmetic ingredients and their safety evaluation. (Non-oxidative conditions) (on head concentration 1.5%) Absorption through the skin A = 2.97 µg/cm² Skin Area surface SAS = 580 cm2 Dermal absorption per treatment SAS x A x 0.001 = 1.723 mg Typical body weight of human = 60 kg Systemic exposure dose (SED) SAS x","endpoint":"dermal absorption","ingredient":"N,N'-bis-(2-Hydroxyethyl)-2-nitro-p-phenylenediamine","loael_value":"","noael_unit":"mg/kg bw/d","noael_value":"= 240","page":36,"route":"oral","species":"rat","study_id":"sccs_o_196_noael_011"}
UnifiedCodex:SCCS_SHADOW:beta.noael_studies	dermal absorption	=120	mg/kg bw/d	rat	oral	90-day	dermal absorption	SOURCE_SUBDIR=sccs_o_196; REPORT_TITLE=OPINION ON N,N'-Bis-(2-hydroxyethyl)-2-nitro-p-phenylenediamine (B34); OPINION_NUMBER=SCCS/1572/16; COMMITTEE=Scientific Committee on Consumer Safety (SCCS); REPORT_DATE=Final version of 16 September 2016; VALUE_TEXT== 120; DOSE=ty evaluation (including calculation of the MoS) CALCULATION OF THE MARGIN OF SAFETY (Oxidative conditions) (on head concentration 1%) Absorption through the skin A = 1.76 µg/cm² Skin Area surface SAS = 580 cm2 Dermal absorption per treatment SAS x A x 0.001 = 1.021 mg Typical body weight of human = 60 kg Systemic exposure dose (SED) SAS x A x 0...; EFFECT=ty evaluation (including calculation of the MoS) CALCULATION OF THE MARGIN OF SAFETY (Oxidative conditions) (on head concentration 1%) Absorption through the skin A = 1.76 µg/cm² Skin Area surface SAS = 580 cm2 Dermal absorption per treatment SAS x A x 0.001 = 1.021 mg Typical body weight of human = 60 kg Systemic exposure dose (SED) SAS x A x 0.001/60 = 0.017 mg/kg bw/d No observed adverse effect level NOAEL = 240 mg/kg bw/d (90-day, oral, rat) Bioavailability 50%* = 120 mg/kg bw/d Margin of Safety adjusted NOAEL/SED = 7100 * standard procedure according to the SCCS's Notes of Guidance for the testing of cosmetic ingredients and their safety evaluation. (Non-oxidative conditions) (on head concentration 1.5%) Absorption through the skin A = 2.97 µg/cm² Skin Area surface SAS = 580 cm2 Dermal absorption per treatment SAS x A x 0.001 = 1.723 mg Typical body weight of human = 60 kg Systemic exposure dose (SED) SAS x A x 0.001/60 = 0.029 mg/kg bw/d No observed adverse effect level NOAEL = 240 mg/kg bw/d (90-day, oral, rat); CITATION_NUMBERS=[]; DETAILS_JSON={"cas_number":"84041-77-0","citation":"","dose":"ty evaluation (including calculation of the MoS) CALCULATION OF THE MARGIN OF SAFETY (Oxidative conditions) (on head concentration 1%) Absorption through the skin A = 1.76 µg/cm² Skin Area surface SAS = 580 cm2 Dermal absorption per treatment SAS x A x 0.001 = 1.021 mg Typical body weight of human = 60 kg Systemic exposure dose (SED) SAS x A x 0...","duration":"90-day","effect":"ty evaluation (including calculation of the MoS) CALCULATION OF THE MARGIN OF SAFETY (Oxidative conditions) (on head concentration 1%) Absorption through the skin A = 1.76 µg/cm² Skin Area surface SAS = 580 cm2 Dermal absorption per treatment SAS x A x 0.001 = 1.021 mg Typical body weight of human = 60 kg Systemic exposure dose (SED) SAS x A x 0.001/60 = 0.017 mg/kg bw/d No observed adverse effect level NOAEL = 240 mg/kg bw/d (90-day, oral, rat) Bioavailability 50%* = 120 mg/kg bw/d Margin of Safety adjusted NOAEL/SED = 7100 * standard procedure according to the SCCS's Notes of Guidance for the testing of cosmetic ingredients and their safety evaluation. (Non-oxidative conditions) (on head concentration 1.5%) Absorption through the skin A = 2.97 µg/cm² Skin Area surface SAS = 580 cm2 Dermal absorption per treatment SAS x A x 0.001 = 1.723 mg Typical body weight of human = 60 kg Systemic exposure dose (SED) SAS x A x 0.001/60 = 0.029 mg/kg bw/d No observed adverse effect level NOAEL = 240 mg/kg bw/d (90-day, oral, rat)","endpoint":"dermal absorption","ingredient":"N,N'-bis-(2-Hydroxyethyl)-2-nitro-p-phenylenediamine","loael_value":"","noael_unit":"mg/kg bw/d","noael_value":"= 120","page":36,"route":"oral","species":"rat","study_id":"sccs_o_196_noael_012"}
UnifiedCodex:SCCS_SHADOW:beta.noael_studies	dermal absorption	=0.029	mg/kg bw/d	rat	oral	90-day	dermal absorption	SOURCE_SUBDIR=sccs_o_196; REPORT_TITLE=OPINION ON N,N'-Bis-(2-hydroxyethyl)-2-nitro-p-phenylenediamine (B34); OPINION_NUMBER=SCCS/1572/16; COMMITTEE=Scientific Committee on Consumer Safety (SCCS); REPORT_DATE=Final version of 16 September 2016; VALUE_TEXT== 0.029; DOSE=rat) Bioavailability 50%* = 120 mg/kg bw/d Margin of Safety adjusted NOAEL/SED = 7100 * standard procedure according to the SCCS's Notes of Guidance for the testing of cosmetic ingredients and their safety evaluation.; EFFECT=rat) Bioavailability 50%* = 120 mg/kg bw/d Margin of Safety adjusted NOAEL/SED = 7100 * standard procedure according to the SCCS's Notes of Guidance for the testing of cosmetic ingredients and their safety evaluation. (Non-oxidative conditions) (on head concentration 1.5%) Absorption through the skin A = 2.97 µg/cm² Skin Area surface SAS = 580 cm2 Dermal absorption per treatment SAS x A x 0.001 = 1.723 mg Typical body weight of human = 60 kg Systemic exposure dose (SED) SAS x A x 0.001/60 = 0.029 mg/kg bw/d No observed adverse effect level NOAEL = 240 mg/kg bw/d (90-day, oral, rat) Bioavailability 50%* = 120 mg/kg bw/d Margin of Safety adjusted NOAEL/SED = 4100 * standard procedure according to the SCCS's Notes of Guidance for the testing of cosmetic ingredients and their safety evaluation. 3.3.14 Discussion Physico-chemical properties N,N’-bis-(2-hydroxyethyl)-2-nitro-p-phenylenediamine is used as a direct hair dye for hair colouring products. It is also used in oxidative hair dye formulations with and without an oxidising agent (e.g. hydrog; CITATION_NUMBERS=[]; DETAILS_JSON={"cas_number":"84041-77-0","citation":"","dose":"rat) Bioavailability 50%* = 120 mg/kg bw/d Margin of Safety adjusted NOAEL/SED = 7100 * standard procedure according to the SCCS's Notes of Guidance for the testing of cosmetic ingredients and their safety evaluation.","duration":"90-day","effect":"rat) Bioavailability 50%* = 120 mg/kg bw/d Margin of Safety adjusted NOAEL/SED = 7100 * standard procedure according to the SCCS's Notes of Guidance for the testing of cosmetic ingredients and their safety evaluation. (Non-oxidative conditions) (on head concentration 1.5%) Absorption through the skin A = 2.97 µg/cm² Skin Area surface SAS = 580 cm2 Dermal absorption per treatment SAS x A x 0.001 = 1.723 mg Typical body weight of human = 60 kg Systemic exposure dose (SED) SAS x A x 0.001/60 = 0.029 mg/kg bw/d No observed adverse effect level NOAEL = 240 mg/kg bw/d (90-day, oral, rat) Bioavailability 50%* = 120 mg/kg bw/d Margin of Safety adjusted NOAEL/SED = 4100 * standard procedure according to the SCCS's Notes of Guidance for the testing of cosmetic ingredients and their safety evaluation. 3.3.14 Discussion Physico-chemical properties N,N’-bis-(2-hydroxyethyl)-2-nitro-p-phenylenediamine is used as a direct hair dye for hair colouring products. It is also used in oxidative hair dye formulations with and without an oxidising agent (e.g. hydrog","endpoint":"dermal absorption","ingredient":"N,N'-bis-(2-Hydroxyethyl)-2-nitro-p-phenylenediamine","loael_value":"","noael_unit":"mg/kg bw/d","noael_value":"= 0.029","page":36,"route":"oral","species":"rat","study_id":"sccs_o_196_noael_013"}
UnifiedCodex:SCCS_SHADOW:beta.noael_studies	dermal absorption	=240	mg/kg bw/d	rat	oral	90-day	dermal absorption	SOURCE_SUBDIR=sccs_o_196; REPORT_TITLE=OPINION ON N,N'-Bis-(2-hydroxyethyl)-2-nitro-p-phenylenediamine (B34); OPINION_NUMBER=SCCS/1572/16; COMMITTEE=Scientific Committee on Consumer Safety (SCCS); REPORT_DATE=Final version of 16 September 2016; VALUE_TEXT== 240; DOSE=mg/kg bw/d Margin of Safety adjusted NOAEL/SED = 7100 * standard procedure according to the SCCS's Notes of Guidance for the testing of cosmetic ingredients and their safety evaluation.; EFFECT=mg/kg bw/d Margin of Safety adjusted NOAEL/SED = 7100 * standard procedure according to the SCCS's Notes of Guidance for the testing of cosmetic ingredients and their safety evaluation. (Non-oxidative conditions) (on head concentration 1.5%) Absorption through the skin A = 2.97 µg/cm² Skin Area surface SAS = 580 cm2 Dermal absorption per treatment SAS x A x 0.001 = 1.723 mg Typical body weight of human = 60 kg Systemic exposure dose (SED) SAS x A x 0.001/60 = 0.029 mg/kg bw/d No observed adverse effect level NOAEL = 240 mg/kg bw/d (90-day, oral, rat) Bioavailability 50%* = 120 mg/kg bw/d Margin of Safety adjusted NOAEL/SED = 4100 * standard procedure according to the SCCS's Notes of Guidance for the testing of cosmetic ingredients and their safety evaluation. 3.3.14 Discussion Physico-chemical properties N,N’-bis-(2-hydroxyethyl)-2-nitro-p-phenylenediamine is used as a direct hair dye for hair colouring products. It is also used in oxidative hair dye formulations with and without an oxidising agent (e.g. hydrogen per; CITATION_NUMBERS=[]; DETAILS_JSON={"cas_number":"84041-77-0","citation":"","dose":"mg/kg bw/d Margin of Safety adjusted NOAEL/SED = 7100 * standard procedure according to the SCCS's Notes of Guidance for the testing of cosmetic ingredients and their safety evaluation.","duration":"90-day","effect":"mg/kg bw/d Margin of Safety adjusted NOAEL/SED = 7100 * standard procedure according to the SCCS's Notes of Guidance for the testing of cosmetic ingredients and their safety evaluation. (Non-oxidative conditions) (on head concentration 1.5%) Absorption through the skin A = 2.97 µg/cm² Skin Area surface SAS = 580 cm2 Dermal absorption per treatment SAS x A x 0.001 = 1.723 mg Typical body weight of human = 60 kg Systemic exposure dose (SED) SAS x A x 0.001/60 = 0.029 mg/kg bw/d No observed adverse effect level NOAEL = 240 mg/kg bw/d (90-day, oral, rat) Bioavailability 50%* = 120 mg/kg bw/d Margin of Safety adjusted NOAEL/SED = 4100 * standard procedure according to the SCCS's Notes of Guidance for the testing of cosmetic ingredients and their safety evaluation. 3.3.14 Discussion Physico-chemical properties N,N’-bis-(2-hydroxyethyl)-2-nitro-p-phenylenediamine is used as a direct hair dye for hair colouring products. It is also used in oxidative hair dye formulations with and without an oxidising agent (e.g. hydrogen per","endpoint":"dermal absorption","ingredient":"N,N'-bis-(2-Hydroxyethyl)-2-nitro-p-phenylenediamine","loael_value":"","noael_unit":"mg/kg bw/d","noael_value":"= 240","page":36,"route":"oral","species":"rat","study_id":"sccs_o_196_noael_014"}
UnifiedCodex:SCCS_SHADOW:beta.noael_studies	dermal absorption	=120	mg/kg bw/d	rat	oral	90-day	dermal absorption	SOURCE_SUBDIR=sccs_o_196; REPORT_TITLE=OPINION ON N,N'-Bis-(2-hydroxyethyl)-2-nitro-p-phenylenediamine (B34); OPINION_NUMBER=SCCS/1572/16; COMMITTEE=Scientific Committee on Consumer Safety (SCCS); REPORT_DATE=Final version of 16 September 2016; VALUE_TEXT== 120; DOSE=(Non-oxidative conditions) (on head concentration 1.5%) Absorption through the skin A = 2.97 µg/cm² Skin Area surface SAS = 580 cm2 Dermal absorption per treatment SAS x A x 0.001 = 1.723 mg Typical body weight of human = 60 kg Systemic exposure dose (SED) SAS x A x 0.001/60 = 0.029 mg/kg bw/d No observed adverse effect level NOAEL = 240 mg/kg b...; EFFECT=Guidance for the testing of cosmetic ingredients and their safety evaluation. (Non-oxidative conditions) (on head concentration 1.5%) Absorption through the skin A = 2.97 µg/cm² Skin Area surface SAS = 580 cm2 Dermal absorption per treatment SAS x A x 0.001 = 1.723 mg Typical body weight of human = 60 kg Systemic exposure dose (SED) SAS x A x 0.001/60 = 0.029 mg/kg bw/d No observed adverse effect level NOAEL = 240 mg/kg bw/d (90-day, oral, rat) Bioavailability 50%* = 120 mg/kg bw/d Margin of Safety adjusted NOAEL/SED = 4100 * standard procedure according to the SCCS's Notes of Guidance for the testing of cosmetic ingredients and their safety evaluation. 3.3.14 Discussion Physico-chemical properties N,N’-bis-(2-hydroxyethyl)-2-nitro-p-phenylenediamine is used as a direct hair dye for hair colouring products. It is also used in oxidative hair dye formulations with and without an oxidising agent (e.g. hydrogen peroxide). The final on-head concentration of N,N’-bis-(2- hydroxyethyl)-2-nitro-p-phenylenediamine can be up to; CITATION_NUMBERS=[]; DETAILS_JSON={"cas_number":"84041-77-0","citation":"","dose":"(Non-oxidative conditions) (on head concentration 1.5%) Absorption through the skin A = 2.97 µg/cm² Skin Area surface SAS = 580 cm2 Dermal absorption per treatment SAS x A x 0.001 = 1.723 mg Typical body weight of human = 60 kg Systemic exposure dose (SED) SAS x A x 0.001/60 = 0.029 mg/kg bw/d No observed adverse effect level NOAEL = 240 mg/kg b...","duration":"90-day","effect":"Guidance for the testing of cosmetic ingredients and their safety evaluation. (Non-oxidative conditions) (on head concentration 1.5%) Absorption through the skin A = 2.97 µg/cm² Skin Area surface SAS = 580 cm2 Dermal absorption per treatment SAS x A x 0.001 = 1.723 mg Typical body weight of human = 60 kg Systemic exposure dose (SED) SAS x A x 0.001/60 = 0.029 mg/kg bw/d No observed adverse effect level NOAEL = 240 mg/kg bw/d (90-day, oral, rat) Bioavailability 50%* = 120 mg/kg bw/d Margin of Safety adjusted NOAEL/SED = 4100 * standard procedure according to the SCCS's Notes of Guidance for the testing of cosmetic ingredients and their safety evaluation. 3.3.14 Discussion Physico-chemical properties N,N’-bis-(2-hydroxyethyl)-2-nitro-p-phenylenediamine is used as a direct hair dye for hair colouring products. It is also used in oxidative hair dye formulations with and without an oxidising agent (e.g. hydrogen peroxide). The final on-head concentration of N,N’-bis-(2- hydroxyethyl)-2-nitro-p-phenylenediamine can be up to","endpoint":"dermal absorption","ingredient":"N,N'-bis-(2-Hydroxyethyl)-2-nitro-p-phenylenediamine","loael_value":"","noael_unit":"mg/kg bw/d","noael_value":"= 120","page":36,"route":"oral","species":"rat","study_id":"sccs_o_196_noael_015"}
UnifiedCodex:SCCS_SHADOW:beta.noael_studies	developmental toxicity	1000	mg/kg	rat	oral	Prenatal	developmental toxicity	SOURCE_SUBDIR=sccs_o_096; REPORT_TITLE=OPINION ON N,N'-bis-(2-Hydroxyethyl)-2-nitro-p-phenylenediamine COLIPA n° B34; OPINION_NUMBER=SCCS/1463/12; COMMITTEE=Scientific Committee on Consumer Safety (SCCS); REPORT_DATE=18 September 2012; VALUE_TEXT=1000; DOSE=SCCS/1463/12 Opinion on N,N'-bis-(2-Hydroxyethyl)-2-nitro-p-phenylenediamine ___________________________________________________________________________________________ 32 unaffected in all dose groups.; EFFECT=SCCS/1463/12 Opinion on N,N'-bis-(2-Hydroxyethyl)-2-nitro-p-phenylenediamine ___________________________________________________________________________________________ 32 unaffected in all dose groups. The incidence of external, visceral, major and minor skeletal abnormalities was not changed by substance treatment. N,N’-bis-(2- hydroxyethyl)-2-nitro- p-phenylenediamine elicited maternal toxicity at 1000 mg/kg, the NOAEL in this study is 100 mg/kg bw/day. The NOAEL of embryotoxicity and teratogenicity is 1000 mg/kg bw/day. Ref.: 21 Prenatal developmental study Guideline: OECD 414 (2001) Species/strain: rat, Wistar Hannover (HsdBrlHan:Wist) Group size: 100 (25 females per dose group) Test substance: B034 Batch: DALA 013106 (SAT 040411) Purity: 99.5% Vehicle: 0.5% aqueous carboxymethylcellulose Dose levels: 0, 300, 600 and 1200 mg/kg bw Dose volume: 10 ml/kg bw Route: oral gavage Administration: once daily from gestation day (GD); CITATION=Ref.: 21 Prenatal developmental study Guideline: OECD 414 (2001) Species/strain: rat, Wistar Hannover (HsdBrlHan:Wist) Group size: 100 (25 females per dose group) Test substance: B034 Ba; CITATION_NUMBERS=[21,414,2001,100,25,34]; REFERENCE=Ref.: 21 Prenatal developmental study Guideline: OECD 414 (2001) Species/strain: rat, Wistar Hannover (HsdBrlHan:Wist) Group size: 100 (25 females per dose group) Test substance: B034 Ba; DETAILS_JSON={"cas_number":"84041-77-0","citation":"Ref.: 21 Prenatal developmental study Guideline: OECD 414 (2001) Species/strain: rat, Wistar Hannover (HsdBrlHan:Wist) Group size: 100 (25 females per dose group) Test substance: B034 Ba","dose":"SCCS/1463/12 Opinion on N,N'-bis-(2-Hydroxyethyl)-2-nitro-p-phenylenediamine ___________________________________________________________________________________________ 32 unaffected in all dose groups.","duration":"Prenatal","effect":"SCCS/1463/12 Opinion on N,N'-bis-(2-Hydroxyethyl)-2-nitro-p-phenylenediamine ___________________________________________________________________________________________ 32 unaffected in all dose groups. The incidence of external, visceral, major and minor skeletal abnormalities was not changed by substance treatment. N,N’-bis-(2- hydroxyethyl)-2-nitro- p-phenylenediamine elicited maternal toxicity at 1000 mg/kg, the NOAEL in this study is 100 mg/kg bw/day. The NOAEL of embryotoxicity and teratogenicity is 1000 mg/kg bw/day. Ref.: 21 Prenatal developmental study Guideline: OECD 414 (2001) Species/strain: rat, Wistar Hannover (HsdBrlHan:Wist) Group size: 100 (25 females per dose group) Test substance: B034 Batch: DALA 013106 (SAT 040411) Purity: 99.5% Vehicle: 0.5% aqueous carboxymethylcellulose Dose levels: 0, 300, 600 and 1200 mg/kg bw Dose volume: 10 ml/kg bw Route: oral gavage Administration: once daily from gestation day (GD)","endpoint":"developmental toxicity","ingredient":"N,N'-bis-(2-Hydroxyethyl)-2-nitro-p-phenylenediamine","loael_value":"","noael_unit":"mg/kg","noael_value":"1000","page":32,"route":"oral","species":"rat","study_id":"sccs_o_096_noael_006"}
UnifiedCodex:SCCS_SHADOW:beta.noael_studies	developmental toxicity	100	mg/kg bw/day	rat	oral	Prenatal	developmental toxicity	SOURCE_SUBDIR=sccs_o_096; REPORT_TITLE=OPINION ON N,N'-bis-(2-Hydroxyethyl)-2-nitro-p-phenylenediamine COLIPA n° B34; OPINION_NUMBER=SCCS/1463/12; COMMITTEE=Scientific Committee on Consumer Safety (SCCS); REPORT_DATE=18 September 2012; VALUE_TEXT=100; DOSE=SCCS/1463/12 Opinion on N,N'-bis-(2-Hydroxyethyl)-2-nitro-p-phenylenediamine ___________________________________________________________________________________________ 32 unaffected in all dose groups.; EFFECT=SCCS/1463/12 Opinion on N,N'-bis-(2-Hydroxyethyl)-2-nitro-p-phenylenediamine ___________________________________________________________________________________________ 32 unaffected in all dose groups. The incidence of external, visceral, major and minor skeletal abnormalities was not changed by substance treatment. N,N’-bis-(2- hydroxyethyl)-2-nitro- p-phenylenediamine elicited maternal toxicity at 1000 mg/kg, the NOAEL in this study is 100 mg/kg bw/day. The NOAEL of embryotoxicity and teratogenicity is 1000 mg/kg bw/day. Ref.: 21 Prenatal developmental study Guideline: OECD 414 (2001) Species/strain: rat, Wistar Hannover (HsdBrlHan:Wist) Group size: 100 (25 females per dose group) Test substance: B034 Batch: DALA 013106 (SAT 040411) Purity: 99.5% Vehicle: 0.5% aqueous carboxymethylcellulose Dose levels: 0, 300, 600 and 1200 mg/kg bw Dose volume: 10 ml/kg bw Route: oral gavage Administration: once daily from gestation day (GD) 5 through day 19 GLP statement: in complianc; CITATION=Ref.: 21 Prenatal developmental study Guideline: OECD 414 (2001) Species/strain: rat, Wistar Hannover (HsdBrlHan:Wist) Group size: 100 (25 females per dose group) Test substance: B034 Ba; CITATION_NUMBERS=[21,414,2001,100,25,34]; REFERENCE=Ref.: 21 Prenatal developmental study Guideline: OECD 414 (2001) Species/strain: rat, Wistar Hannover (HsdBrlHan:Wist) Group size: 100 (25 females per dose group) Test substance: B034 Ba; DETAILS_JSON={"cas_number":"84041-77-0","citation":"Ref.: 21 Prenatal developmental study Guideline: OECD 414 (2001) Species/strain: rat, Wistar Hannover (HsdBrlHan:Wist) Group size: 100 (25 females per dose group) Test substance: B034 Ba","dose":"SCCS/1463/12 Opinion on N,N'-bis-(2-Hydroxyethyl)-2-nitro-p-phenylenediamine ___________________________________________________________________________________________ 32 unaffected in all dose groups.","duration":"Prenatal","effect":"SCCS/1463/12 Opinion on N,N'-bis-(2-Hydroxyethyl)-2-nitro-p-phenylenediamine ___________________________________________________________________________________________ 32 unaffected in all dose groups. The incidence of external, visceral, major and minor skeletal abnormalities was not changed by substance treatment. N,N’-bis-(2- hydroxyethyl)-2-nitro- p-phenylenediamine elicited maternal toxicity at 1000 mg/kg, the NOAEL in this study is 100 mg/kg bw/day. The NOAEL of embryotoxicity and teratogenicity is 1000 mg/kg bw/day. Ref.: 21 Prenatal developmental study Guideline: OECD 414 (2001) Species/strain: rat, Wistar Hannover (HsdBrlHan:Wist) Group size: 100 (25 females per dose group) Test substance: B034 Batch: DALA 013106 (SAT 040411) Purity: 99.5% Vehicle: 0.5% aqueous carboxymethylcellulose Dose levels: 0, 300, 600 and 1200 mg/kg bw Dose volume: 10 ml/kg bw Route: oral gavage Administration: once daily from gestation day (GD) 5 through day 19 GLP statement: in complianc","endpoint":"developmental toxicity","ingredient":"N,N'-bis-(2-Hydroxyethyl)-2-nitro-p-phenylenediamine","loael_value":"","noael_unit":"mg/kg bw/day","noael_value":"100","page":32,"route":"oral","species":"rat","study_id":"sccs_o_096_noael_007"}
UnifiedCodex:SCCS_SHADOW:beta.noael_studies	developmental toxicity	1000	mg/kg	rat	-	Developmental	developmental toxicity	SOURCE_SUBDIR=sccs_o_196; REPORT_TITLE=OPINION ON N,N'-Bis-(2-hydroxyethyl)-2-nitro-p-phenylenediamine (B34); OPINION_NUMBER=SCCS/1572/16; COMMITTEE=Scientific Committee on Consumer Safety (SCCS); REPORT_DATE=Final version of 16 September 2016; VALUE_TEXT=1000; DOSE=In the high-dose group, maternal food consumption and body weight gain were significantly reduced while the slightly lower body weight gain compared to controls in the 100 mg/kg bw/day group was not statistically significant.; EFFECT=ated groups. In the high-dose group, maternal food consumption and body weight gain were significantly reduced while the slightly lower body weight gain compared to controls in the 100 mg/kg bw/day group was not statistically significant. Reproduction parameters remained unaffected in all dose groups. The incidence of external, visceral, major and minor skeletal abnormalities was not changed by substance treatment. N,N’-bis-(2- hydroxyethyl)-2-nitro- p-phenylenediamine elicited maternal toxicity at 1000 mg/kg, the NOAEL in this study is 100 mg/kg bw/day. The NOAEL of embryotoxicity and teratogenicity is 1000 mg/kg bw/day. Ref.: 20, submission I 3.3.8.3 Developmental Toxicity From submission III Prenatal developmental study Guideline: OECD 414 (2001) Species/strain: rat, Wistar Hannover (HsdBrlHan:Wist) Group size: 100 (25 females per dose group) Test substance: B034 Batch: DALA 013106 (SAT 040411) Purity: 99.5% Vehicle: 0.5% aqueous carboxymethylcellulose Dose levels: 0, 300, 600 and 1200 mg/kg bw Dose volume: 10 ml/kg bw Ro; CITATION=Ref.: 20, submission I 3; CITATION_NUMBERS=[20,3]; REFERENCE=Ref.: 20, submission I 3; DETAILS_JSON={"cas_number":"84041-77-0","citation":"Ref.: 20, submission I 3","dose":"In the high-dose group, maternal food consumption and body weight gain were significantly reduced while the slightly lower body weight gain compared to controls in the 100 mg/kg bw/day group was not statistically significant.","duration":"Developmental","effect":"ated groups. In the high-dose group, maternal food consumption and body weight gain were significantly reduced while the slightly lower body weight gain compared to controls in the 100 mg/kg bw/day group was not statistically significant. Reproduction parameters remained unaffected in all dose groups. The incidence of external, visceral, major and minor skeletal abnormalities was not changed by substance treatment. N,N’-bis-(2- hydroxyethyl)-2-nitro- p-phenylenediamine elicited maternal toxicity at 1000 mg/kg, the NOAEL in this study is 100 mg/kg bw/day. The NOAEL of embryotoxicity and teratogenicity is 1000 mg/kg bw/day. Ref.: 20, submission I 3.3.8.3 Developmental Toxicity From submission III Prenatal developmental study Guideline: OECD 414 (2001) Species/strain: rat, Wistar Hannover (HsdBrlHan:Wist) Group size: 100 (25 females per dose group) Test substance: B034 Batch: DALA 013106 (SAT 040411) Purity: 99.5% Vehicle: 0.5% aqueous carboxymethylcellulose Dose levels: 0, 300, 600 and 1200 mg/kg bw Dose volume: 10 ml/kg bw Ro","endpoint":"developmental toxicity","ingredient":"N,N'-bis-(2-Hydroxyethyl)-2-nitro-p-phenylenediamine","loael_value":"","noael_unit":"mg/kg","noael_value":"1000","page":33,"route":"","species":"rat","study_id":"sccs_o_196_noael_006"}
UnifiedCodex:SCCS_SHADOW:beta.noael_studies	developmental toxicity	100	mg/kg bw/day	rat	oral	Developmental	developmental toxicity	SOURCE_SUBDIR=sccs_o_196; REPORT_TITLE=OPINION ON N,N'-Bis-(2-hydroxyethyl)-2-nitro-p-phenylenediamine (B34); OPINION_NUMBER=SCCS/1572/16; COMMITTEE=Scientific Committee on Consumer Safety (SCCS); REPORT_DATE=Final version of 16 September 2016; VALUE_TEXT=100; DOSE=food consumption and body weight gain were significantly reduced while the slightly lower body weight gain compared to controls in the 100 mg/kg bw/day group was not statistically significant.; EFFECT=food consumption and body weight gain were significantly reduced while the slightly lower body weight gain compared to controls in the 100 mg/kg bw/day group was not statistically significant. Reproduction parameters remained unaffected in all dose groups. The incidence of external, visceral, major and minor skeletal abnormalities was not changed by substance treatment. N,N’-bis-(2- hydroxyethyl)-2-nitro- p-phenylenediamine elicited maternal toxicity at 1000 mg/kg, the NOAEL in this study is 100 mg/kg bw/day. The NOAEL of embryotoxicity and teratogenicity is 1000 mg/kg bw/day. Ref.: 20, submission I 3.3.8.3 Developmental Toxicity From submission III Prenatal developmental study Guideline: OECD 414 (2001) Species/strain: rat, Wistar Hannover (HsdBrlHan:Wist) Group size: 100 (25 females per dose group) Test substance: B034 Batch: DALA 013106 (SAT 040411) Purity: 99.5% Vehicle: 0.5% aqueous carboxymethylcellulose Dose levels: 0, 300, 600 and 1200 mg/kg bw Dose volume: 10 ml/kg bw Route: oral gavage Administration: once daily f; CITATION=Ref.: 20, submission I 3; CITATION_NUMBERS=[20,3]; REFERENCE=Ref.: 20, submission I 3; DETAILS_JSON={"cas_number":"84041-77-0","citation":"Ref.: 20, submission I 3","dose":"food consumption and body weight gain were significantly reduced while the slightly lower body weight gain compared to controls in the 100 mg/kg bw/day group was not statistically significant.","duration":"Developmental","effect":"food consumption and body weight gain were significantly reduced while the slightly lower body weight gain compared to controls in the 100 mg/kg bw/day group was not statistically significant. Reproduction parameters remained unaffected in all dose groups. The incidence of external, visceral, major and minor skeletal abnormalities was not changed by substance treatment. N,N’-bis-(2- hydroxyethyl)-2-nitro- p-phenylenediamine elicited maternal toxicity at 1000 mg/kg, the NOAEL in this study is 100 mg/kg bw/day. The NOAEL of embryotoxicity and teratogenicity is 1000 mg/kg bw/day. Ref.: 20, submission I 3.3.8.3 Developmental Toxicity From submission III Prenatal developmental study Guideline: OECD 414 (2001) Species/strain: rat, Wistar Hannover (HsdBrlHan:Wist) Group size: 100 (25 females per dose group) Test substance: B034 Batch: DALA 013106 (SAT 040411) Purity: 99.5% Vehicle: 0.5% aqueous carboxymethylcellulose Dose levels: 0, 300, 600 and 1200 mg/kg bw Dose volume: 10 ml/kg bw Route: oral gavage Administration: once daily f","endpoint":"developmental toxicity","ingredient":"N,N'-bis-(2-Hydroxyethyl)-2-nitro-p-phenylenediamine","loael_value":"","noael_unit":"mg/kg bw/day","noael_value":"100","page":33,"route":"oral","species":"rat","study_id":"sccs_o_196_noael_007"}
UnifiedCodex:SCCS_SHADOW:beta.noael_studies	genotoxicity	240	mg/kg/day	-	-	Chronic	genotoxicity	SOURCE_SUBDIR=sccs_o_019; REPORT_TITLE=OPINION ON N,N'-bis-(2-Hydroxyethyl)-2-nitro-p-phenylenediamine COLIPA n° B34; OPINION_NUMBER=SCCS/1228/09; COMMITTEE=Scientific Committee on Consumer Safety (SCCS); REPORT_DATE=12 July 2010; VALUE_TEXT=240; DOSE=SCCS/1228/09, revision of 12.07.10 Opinion on N,N'-bis-(2-Hydroxyethyl)-2-nitro-p-phenylenediamine __________________________________________________________________________________ 16 Conclusion On the basis of these results, the mid-dose (240 mg/kg/day) may be considered the No Observed Adverse Effect Level (NOAEL) for N,N’-bis-(2-hydroxyethyl...; EFFECT=SCCS/1228/09, revision of 12.07.10 Opinion on N,N'-bis-(2-Hydroxyethyl)-2-nitro-p-phenylenediamine __________________________________________________________________________________ 16 Conclusion On the basis of these results, the mid-dose (240 mg/kg/day) may be considered the No Observed Adverse Effect Level (NOAEL) for N,N’-bis-(2-hydroxyethyl)-2-nitro-p- phenylenediamine. Ref.: 11 3.3.5.3. Chronic (> 12 months) toxicity No data submitted 3.3.6. Mutagenicity / Genotoxicity 3.3.6.1 Mutagenicity / Genotoxicity in vitro Taken from SCCNFP/0781/04 Reverse Mutation Testing Using Bacteria Guideline: OECD 471 (1983) Species/Strain: Salmonella typhimurium (TA98, TA98 NR) Test item: HC Violet B5 Batch: / Purity: / Replicate: 2 experiments Doses: 100, 500, 1000, 2500, 5000, 7500, 10000 μg/plate Metabolic Act.: Phenobarbi; CITATION=Ref.: 11 3; CITATION_NUMBERS=[11,3]; REFERENCE=Ref.: 11 3; DETAILS_JSON={"cas_number":"84041-77-0","citation":"Ref.: 11 3","dose":"SCCS/1228/09, revision of 12.07.10 Opinion on N,N'-bis-(2-Hydroxyethyl)-2-nitro-p-phenylenediamine __________________________________________________________________________________ 16 Conclusion On the basis of these results, the mid-dose (240 mg/kg/day) may be considered the No Observed Adverse Effect Level (NOAEL) for N,N’-bis-(2-hydroxyethyl...","duration":"Chronic","effect":"SCCS/1228/09, revision of 12.07.10 Opinion on N,N'-bis-(2-Hydroxyethyl)-2-nitro-p-phenylenediamine __________________________________________________________________________________ 16 Conclusion On the basis of these results, the mid-dose (240 mg/kg/day) may be considered the No Observed Adverse Effect Level (NOAEL) for N,N’-bis-(2-hydroxyethyl)-2-nitro-p- phenylenediamine. Ref.: 11 3.3.5.3. Chronic (> 12 months) toxicity No data submitted 3.3.6. Mutagenicity / Genotoxicity 3.3.6.1 Mutagenicity / Genotoxicity in vitro Taken from SCCNFP/0781/04 Reverse Mutation Testing Using Bacteria Guideline: OECD 471 (1983) Species/Strain: Salmonella typhimurium (TA98, TA98 NR) Test item: HC Violet B5 Batch: / Purity: / Replicate: 2 experiments Doses: 100, 500, 1000, 2500, 5000, 7500, 10000 μg/plate Metabolic Act.: Phenobarbi","endpoint":"genotoxicity","ingredient":"N,N'-bis-(2-Hydroxyethyl)-2-nitro-p-phenylenediamine","loael_value":"","noael_unit":"mg/kg/day","noael_value":"240","page":16,"route":"","species":"","study_id":"sccs_o_019_noael_001"}
UnifiedCodex:SCCS_SHADOW:beta.noael_studies	genotoxicity	240	mg/kg/day	-	-	Chronic	genotoxicity	SOURCE_SUBDIR=sccs_o_096; REPORT_TITLE=OPINION ON N,N'-bis-(2-Hydroxyethyl)-2-nitro-p-phenylenediamine COLIPA n° B34; OPINION_NUMBER=SCCS/1463/12; COMMITTEE=Scientific Committee on Consumer Safety (SCCS); REPORT_DATE=18 September 2012; VALUE_TEXT=240; DOSE=By the end of the recovery period, the distribution of these deposits was multi-focal in the treated animals and focal in the controls.; EFFECT=ose- related increase in the incidence of yellow-brown, intra-cytoplasmic pigmentation. These deposits were not evaluated as an adverse effect, since no toxicologically significant differences were observed in the accumulation of pigment deposits. By the end of the recovery period, the distribution of these deposits was multi-focal in the treated animals and focal in the controls. No other organ was affected by treatment. Conclusion On the basis of these results, the mid-dose (240 mg/kg/day) may be considered the No Observed Adverse Effect Level (NOAEL) for N,N’-bis-(2-hydroxyethyl)-2-nitro-p- phenylenediamine. Ref.: 11 Comment The NOAEL of 240 mg/kg bw/d could be used for the calculation of the Margin of Safety (MoS). 3.3.5.3. Chronic (> 12 months) toxicity No data submitted 3.3.6. Mutagenicity / Genotoxicity 3.3.6.1 Mutagenicity / Genotoxicity in vitro Taken from SCCNFP/0781/04, modified Reverse Mutation Testing Using Bacteria Guideline: OECD 471 (1983) Species/Strain: Salmonella typhimurium TA98 and TA98 NR Replicates: triplicates in 2 experime; CITATION=Ref.: 11 Comment The NOAEL of 240 mg/kg bw/d could be used for the calculation of the Margin of Safety (MoS); CITATION_NUMBERS=[11,240]; REFERENCE=Ref.: 11 Comment The NOAEL of 240 mg/kg bw/d could be used for the calculation of the Margin of Safety (MoS); DETAILS_JSON={"cas_number":"84041-77-0","citation":"Ref.: 11 Comment The NOAEL of 240 mg/kg bw/d could be used for the calculation of the Margin of Safety (MoS)","dose":"By the end of the recovery period, the distribution of these deposits was multi-focal in the treated animals and focal in the controls.","duration":"Chronic","effect":"ose- related increase in the incidence of yellow-brown, intra-cytoplasmic pigmentation. These deposits were not evaluated as an adverse effect, since no toxicologically significant differences were observed in the accumulation of pigment deposits. By the end of the recovery period, the distribution of these deposits was multi-focal in the treated animals and focal in the controls. No other organ was affected by treatment. Conclusion On the basis of these results, the mid-dose (240 mg/kg/day) may be considered the No Observed Adverse Effect Level (NOAEL) for N,N’-bis-(2-hydroxyethyl)-2-nitro-p- phenylenediamine. Ref.: 11 Comment The NOAEL of 240 mg/kg bw/d could be used for the calculation of the Margin of Safety (MoS). 3.3.5.3. Chronic (> 12 months) toxicity No data submitted 3.3.6. Mutagenicity / Genotoxicity 3.3.6.1 Mutagenicity / Genotoxicity in vitro Taken from SCCNFP/0781/04, modified Reverse Mutation Testing Using Bacteria Guideline: OECD 471 (1983) Species/Strain: Salmonella typhimurium TA98 and TA98 NR Replicates: triplicates in 2 experime","endpoint":"genotoxicity","ingredient":"N,N'-bis-(2-Hydroxyethyl)-2-nitro-p-phenylenediamine","loael_value":"","noael_unit":"mg/kg/day","noael_value":"240","page":17,"route":"","species":"","study_id":"sccs_o_096_noael_003"}
UnifiedCodex:SCCS_SHADOW:beta.noael_studies	genotoxicity	240	mg/kg/day	-	-	Chronic	genotoxicity	SOURCE_SUBDIR=sccs_o_096; REPORT_TITLE=OPINION ON N,N'-bis-(2-Hydroxyethyl)-2-nitro-p-phenylenediamine COLIPA n° B34; OPINION_NUMBER=SCCS/1463/12; COMMITTEE=Scientific Committee on Consumer Safety (SCCS); REPORT_DATE=18 September 2012; VALUE_TEXT=240; DOSE=By the end of the recovery period, the distribution of these deposits was multi-focal in the treated animals and focal in the controls.; EFFECT=ence of yellow-brown, intra-cytoplasmic pigmentation. These deposits were not evaluated as an adverse effect, since no toxicologically significant differences were observed in the accumulation of pigment deposits. By the end of the recovery period, the distribution of these deposits was multi-focal in the treated animals and focal in the controls. No other organ was affected by treatment. Conclusion On the basis of these results, the mid-dose (240 mg/kg/day) may be considered the No Observed Adverse Effect Level (NOAEL) for N,N’-bis-(2-hydroxyethyl)-2-nitro-p- phenylenediamine. Ref.: 11 Comment The NOAEL of 240 mg/kg bw/d could be used for the calculation of the Margin of Safety (MoS). 3.3.5.3. Chronic (> 12 months) toxicity No data submitted 3.3.6. Mutagenicity / Genotoxicity 3.3.6.1 Mutagenicity / Genotoxicity in vitro Taken from SCCNFP/0781/04, modified Reverse Mutation Testing Using Bacteria Guideline: OECD 471 (1983) Species/Strain: Salmonella typhimurium TA98 and TA98 NR Replicates: triplicates in 2 experiments Tes; CITATION=Ref.: 11 Comment The NOAEL of 240 mg/kg bw/d could be used for the calculation of the Margin of Safety (MoS); CITATION_NUMBERS=[11,240]; REFERENCE=Ref.: 11 Comment The NOAEL of 240 mg/kg bw/d could be used for the calculation of the Margin of Safety (MoS); DETAILS_JSON={"cas_number":"84041-77-0","citation":"Ref.: 11 Comment The NOAEL of 240 mg/kg bw/d could be used for the calculation of the Margin of Safety (MoS)","dose":"By the end of the recovery period, the distribution of these deposits was multi-focal in the treated animals and focal in the controls.","duration":"Chronic","effect":"ence of yellow-brown, intra-cytoplasmic pigmentation. These deposits were not evaluated as an adverse effect, since no toxicologically significant differences were observed in the accumulation of pigment deposits. By the end of the recovery period, the distribution of these deposits was multi-focal in the treated animals and focal in the controls. No other organ was affected by treatment. Conclusion On the basis of these results, the mid-dose (240 mg/kg/day) may be considered the No Observed Adverse Effect Level (NOAEL) for N,N’-bis-(2-hydroxyethyl)-2-nitro-p- phenylenediamine. Ref.: 11 Comment The NOAEL of 240 mg/kg bw/d could be used for the calculation of the Margin of Safety (MoS). 3.3.5.3. Chronic (> 12 months) toxicity No data submitted 3.3.6. Mutagenicity / Genotoxicity 3.3.6.1 Mutagenicity / Genotoxicity in vitro Taken from SCCNFP/0781/04, modified Reverse Mutation Testing Using Bacteria Guideline: OECD 471 (1983) Species/Strain: Salmonella typhimurium TA98 and TA98 NR Replicates: triplicates in 2 experiments Tes","endpoint":"genotoxicity","ingredient":"N,N'-bis-(2-Hydroxyethyl)-2-nitro-p-phenylenediamine","loael_value":"","noael_unit":"mg/kg/day","noael_value":"240","page":17,"route":"","species":"","study_id":"sccs_o_096_noael_004"}
UnifiedCodex:SCCS_SHADOW:beta.noael_studies	genotoxicity	240	mg/kg bw/d	-	-	Chronic	genotoxicity	SOURCE_SUBDIR=sccs_o_096; REPORT_TITLE=OPINION ON N,N'-bis-(2-Hydroxyethyl)-2-nitro-p-phenylenediamine COLIPA n° B34; OPINION_NUMBER=SCCS/1463/12; COMMITTEE=Scientific Committee on Consumer Safety (SCCS); REPORT_DATE=18 September 2012; VALUE_TEXT=240; DOSE=By the end of the recovery period, the distribution of these deposits was multi-focal in the treated animals and focal in the controls.; EFFECT=as an adverse effect, since no toxicologically significant differences were observed in the accumulation of pigment deposits. By the end of the recovery period, the distribution of these deposits was multi-focal in the treated animals and focal in the controls. No other organ was affected by treatment. Conclusion On the basis of these results, the mid-dose (240 mg/kg/day) may be considered the No Observed Adverse Effect Level (NOAEL) for N,N’-bis-(2-hydroxyethyl)-2-nitro-p- phenylenediamine. Ref.: 11 Comment The NOAEL of 240 mg/kg bw/d could be used for the calculation of the Margin of Safety (MoS). 3.3.5.3. Chronic (> 12 months) toxicity No data submitted 3.3.6. Mutagenicity / Genotoxicity 3.3.6.1 Mutagenicity / Genotoxicity in vitro Taken from SCCNFP/0781/04, modified Reverse Mutation Testing Using Bacteria Guideline: OECD 471 (1983) Species/Strain: Salmonella typhimurium TA98 and TA98 NR Replicates: triplicates in 2 experiments Test substance: B 034 Batch: WSI – 75 h/52 Purity: 99.3% Vehicle: DMSO Concentration: 100,; CITATION=Ref.: 11 Comment The NOAEL of 240 mg/kg bw/d could be used for the calculation of the Margin of Safety (MoS); CITATION_NUMBERS=[11,240]; REFERENCE=Ref.: 11 Comment The NOAEL of 240 mg/kg bw/d could be used for the calculation of the Margin of Safety (MoS); DETAILS_JSON={"cas_number":"84041-77-0","citation":"Ref.: 11 Comment The NOAEL of 240 mg/kg bw/d could be used for the calculation of the Margin of Safety (MoS)","dose":"By the end of the recovery period, the distribution of these deposits was multi-focal in the treated animals and focal in the controls.","duration":"Chronic","effect":"as an adverse effect, since no toxicologically significant differences were observed in the accumulation of pigment deposits. By the end of the recovery period, the distribution of these deposits was multi-focal in the treated animals and focal in the controls. No other organ was affected by treatment. Conclusion On the basis of these results, the mid-dose (240 mg/kg/day) may be considered the No Observed Adverse Effect Level (NOAEL) for N,N’-bis-(2-hydroxyethyl)-2-nitro-p- phenylenediamine. Ref.: 11 Comment The NOAEL of 240 mg/kg bw/d could be used for the calculation of the Margin of Safety (MoS). 3.3.5.3. Chronic (> 12 months) toxicity No data submitted 3.3.6. Mutagenicity / Genotoxicity 3.3.6.1 Mutagenicity / Genotoxicity in vitro Taken from SCCNFP/0781/04, modified Reverse Mutation Testing Using Bacteria Guideline: OECD 471 (1983) Species/Strain: Salmonella typhimurium TA98 and TA98 NR Replicates: triplicates in 2 experiments Test substance: B 034 Batch: WSI – 75 h/52 Purity: 99.3% Vehicle: DMSO Concentration: 100,","endpoint":"genotoxicity","ingredient":"N,N'-bis-(2-Hydroxyethyl)-2-nitro-p-phenylenediamine","loael_value":"","noael_unit":"mg/kg bw/d","noael_value":"240","page":17,"route":"","species":"","study_id":"sccs_o_096_noael_005"}
UnifiedCodex:SCCS_SHADOW:beta.noael_studies	irritation	240	mg/kg/day	-	-	90 day	irritation	SOURCE_SUBDIR=sccs_o_019; REPORT_TITLE=OPINION ON N,N'-bis-(2-Hydroxyethyl)-2-nitro-p-phenylenediamine COLIPA n° B34; OPINION_NUMBER=SCCS/1228/09; COMMITTEE=Scientific Committee on Consumer Safety (SCCS); REPORT_DATE=12 July 2010; VALUE_TEXT=240; DOSE=Toxicity The No Observed Adverse Effect Level (NOAEL) for N,N’-bis-(2-hydroxyethyl)-2-nitro-p- phenylenediamine in the 90 day study was considered to be 240 mg/kg/day, based on effects on kidney, which seemed to be the target organ.; EFFECT=(2-hydroxyethyl)-2-nitro-p-phenylenediamine is a secondary amine. It should not be used in the presence of nitrosating agents. The study report of the determination of nitrosamine in N,N’-bis-(2-hydroxyethyl)-2-nitro-p-phenylenediamine described only the principle of the analytical method used and the result. No analytical details and/or analytical data were provided. No data on the stability of N,N’-bis-(2-hydroxyethyl)-2-nitro-p- phenylenediamine in typical hair dye formulations has been provided. Toxicity The No Observed Adverse Effect Level (NOAEL) for N,N’-bis-(2-hydroxyethyl)-2-nitro-p- phenylenediamine in the 90 day study was considered to be 240 mg/kg/day, based on effects on kidney, which seemed to be the target organ. Since no maternal toxicity, foetal toxicity or teratogenicity was seen, the No Observed Adverse Effect Level (NOAEL) for N,N’-bis-(2-hydroxyethyl)-2-nitro-p-phenylenediamine for these endpoints was considered to be 1200 mg/kg/day. No two generation reproduction study was submitted. Skin/eye irritation and sensitisation Neat N,N’; CITATION_NUMBERS=[]; DETAILS_JSON={"cas_number":"84041-77-0","citation":"","dose":"Toxicity The No Observed Adverse Effect Level (NOAEL) for N,N’-bis-(2-hydroxyethyl)-2-nitro-p- phenylenediamine in the 90 day study was considered to be 240 mg/kg/day, based on effects on kidney, which seemed to be the target organ.","duration":"90 day","effect":"(2-hydroxyethyl)-2-nitro-p-phenylenediamine is a secondary amine. It should not be used in the presence of nitrosating agents. The study report of the determination of nitrosamine in N,N’-bis-(2-hydroxyethyl)-2-nitro-p-phenylenediamine described only the principle of the analytical method used and the result. No analytical details and/or analytical data were provided. No data on the stability of N,N’-bis-(2-hydroxyethyl)-2-nitro-p- phenylenediamine in typical hair dye formulations has been provided. Toxicity The No Observed Adverse Effect Level (NOAEL) for N,N’-bis-(2-hydroxyethyl)-2-nitro-p- phenylenediamine in the 90 day study was considered to be 240 mg/kg/day, based on effects on kidney, which seemed to be the target organ. Since no maternal toxicity, foetal toxicity or teratogenicity was seen, the No Observed Adverse Effect Level (NOAEL) for N,N’-bis-(2-hydroxyethyl)-2-nitro-p-phenylenediamine for these endpoints was considered to be 1200 mg/kg/day. No two generation reproduction study was submitted. Skin/eye irritation and sensitisation Neat N,N’","endpoint":"irritation","ingredient":"N,N'-bis-(2-Hydroxyethyl)-2-nitro-p-phenylenediamine","loael_value":"","noael_unit":"mg/kg/day","noael_value":"240","page":28,"route":"","species":"","study_id":"sccs_o_019_noael_004"}
UnifiedCodex:SCCS_SHADOW:beta.noael_studies	irritation	240	mg/kg/day	-	-	90 day	irritation	SOURCE_SUBDIR=sccs_o_019; REPORT_TITLE=OPINION ON N,N'-bis-(2-Hydroxyethyl)-2-nitro-p-phenylenediamine COLIPA n° B34; OPINION_NUMBER=SCCS/1228/09; COMMITTEE=Scientific Committee on Consumer Safety (SCCS); REPORT_DATE=12 July 2010; VALUE_TEXT=240; DOSE=Toxicity The No Observed Adverse Effect Level (NOAEL) for N,N’-bis-(2-hydroxyethyl)-2-nitro-p- phenylenediamine in the 90 day study was considered to be 240 mg/kg/day, based on effects on kidney, which seemed to be the target organ.; EFFECT=nediamine is a secondary amine. It should not be used in the presence of nitrosating agents. The study report of the determination of nitrosamine in N,N’-bis-(2-hydroxyethyl)-2-nitro-p-phenylenediamine described only the principle of the analytical method used and the result. No analytical details and/or analytical data were provided. No data on the stability of N,N’-bis-(2-hydroxyethyl)-2-nitro-p- phenylenediamine in typical hair dye formulations has been provided. Toxicity The No Observed Adverse Effect Level (NOAEL) for N,N’-bis-(2-hydroxyethyl)-2-nitro-p- phenylenediamine in the 90 day study was considered to be 240 mg/kg/day, based on effects on kidney, which seemed to be the target organ. Since no maternal toxicity, foetal toxicity or teratogenicity was seen, the No Observed Adverse Effect Level (NOAEL) for N,N’-bis-(2-hydroxyethyl)-2-nitro-p-phenylenediamine for these endpoints was considered to be 1200 mg/kg/day. No two generation reproduction study was submitted. Skin/eye irritation and sensitisation Neat N,N’-bis-(2; CITATION_NUMBERS=[]; DETAILS_JSON={"cas_number":"84041-77-0","citation":"","dose":"Toxicity The No Observed Adverse Effect Level (NOAEL) for N,N’-bis-(2-hydroxyethyl)-2-nitro-p- phenylenediamine in the 90 day study was considered to be 240 mg/kg/day, based on effects on kidney, which seemed to be the target organ.","duration":"90 day","effect":"nediamine is a secondary amine. It should not be used in the presence of nitrosating agents. The study report of the determination of nitrosamine in N,N’-bis-(2-hydroxyethyl)-2-nitro-p-phenylenediamine described only the principle of the analytical method used and the result. No analytical details and/or analytical data were provided. No data on the stability of N,N’-bis-(2-hydroxyethyl)-2-nitro-p- phenylenediamine in typical hair dye formulations has been provided. Toxicity The No Observed Adverse Effect Level (NOAEL) for N,N’-bis-(2-hydroxyethyl)-2-nitro-p- phenylenediamine in the 90 day study was considered to be 240 mg/kg/day, based on effects on kidney, which seemed to be the target organ. Since no maternal toxicity, foetal toxicity or teratogenicity was seen, the No Observed Adverse Effect Level (NOAEL) for N,N’-bis-(2-hydroxyethyl)-2-nitro-p-phenylenediamine for these endpoints was considered to be 1200 mg/kg/day. No two generation reproduction study was submitted. Skin/eye irritation and sensitisation Neat N,N’-bis-(2","endpoint":"irritation","ingredient":"N,N'-bis-(2-Hydroxyethyl)-2-nitro-p-phenylenediamine","loael_value":"","noael_unit":"mg/kg/day","noael_value":"240","page":28,"route":"","species":"","study_id":"sccs_o_019_noael_005"}
UnifiedCodex:SCCS_SHADOW:beta.noael_studies	irritation	1200	mg/kg/day	mouse	-	90 day	irritation	SOURCE_SUBDIR=sccs_o_019; REPORT_TITLE=OPINION ON N,N'-bis-(2-Hydroxyethyl)-2-nitro-p-phenylenediamine COLIPA n° B34; OPINION_NUMBER=SCCS/1228/09; COMMITTEE=Scientific Committee on Consumer Safety (SCCS); REPORT_DATE=12 July 2010; VALUE_TEXT=1200; DOSE=Toxicity The No Observed Adverse Effect Level (NOAEL) for N,N’-bis-(2-hydroxyethyl)-2-nitro-p- phenylenediamine in the 90 day study was considered to be 240 mg/kg/day, based on effects on kidney, which seemed to be the target organ.; EFFECT=nd the result. No analytical details and/or analytical data were provided. No data on the stability of N,N’-bis-(2-hydroxyethyl)-2-nitro-p- phenylenediamine in typical hair dye formulations has been provided. Toxicity The No Observed Adverse Effect Level (NOAEL) for N,N’-bis-(2-hydroxyethyl)-2-nitro-p- phenylenediamine in the 90 day study was considered to be 240 mg/kg/day, based on effects on kidney, which seemed to be the target organ. Since no maternal toxicity, foetal toxicity or teratogenicity was seen, the No Observed Adverse Effect Level (NOAEL) for N,N’-bis-(2-hydroxyethyl)-2-nitro-p-phenylenediamine for these endpoints was considered to be 1200 mg/kg/day. No two generation reproduction study was submitted. Skin/eye irritation and sensitisation Neat N,N’-bis-(2-hydroxyethyl)-2-nitro-p-phenylenediamine was not irritant when applied to rabbit skin. However, it was noted that 10% N,N’-bis-(2-hydroxyethyl)-2-nitro-p- phenylenediamine in acetone:olive oil was slightly irritant to the mouse ear in the LLNA test. It was irritant to rabbit eyes. N,N’-b; CITATION_NUMBERS=[]; DETAILS_JSON={"cas_number":"84041-77-0","citation":"","dose":"Toxicity The No Observed Adverse Effect Level (NOAEL) for N,N’-bis-(2-hydroxyethyl)-2-nitro-p- phenylenediamine in the 90 day study was considered to be 240 mg/kg/day, based on effects on kidney, which seemed to be the target organ.","duration":"90 day","effect":"nd the result. No analytical details and/or analytical data were provided. No data on the stability of N,N’-bis-(2-hydroxyethyl)-2-nitro-p- phenylenediamine in typical hair dye formulations has been provided. Toxicity The No Observed Adverse Effect Level (NOAEL) for N,N’-bis-(2-hydroxyethyl)-2-nitro-p- phenylenediamine in the 90 day study was considered to be 240 mg/kg/day, based on effects on kidney, which seemed to be the target organ. Since no maternal toxicity, foetal toxicity or teratogenicity was seen, the No Observed Adverse Effect Level (NOAEL) for N,N’-bis-(2-hydroxyethyl)-2-nitro-p-phenylenediamine for these endpoints was considered to be 1200 mg/kg/day. No two generation reproduction study was submitted. Skin/eye irritation and sensitisation Neat N,N’-bis-(2-hydroxyethyl)-2-nitro-p-phenylenediamine was not irritant when applied to rabbit skin. However, it was noted that 10% N,N’-bis-(2-hydroxyethyl)-2-nitro-p- phenylenediamine in acetone:olive oil was slightly irritant to the mouse ear in the LLNA test. It was irritant to rabbit eyes. N,N’-b","endpoint":"irritation","ingredient":"N,N'-bis-(2-Hydroxyethyl)-2-nitro-p-phenylenediamine","loael_value":"","noael_unit":"mg/kg/day","noael_value":"1200","page":28,"route":"","species":"mouse","study_id":"sccs_o_019_noael_006"}
UnifiedCodex:SCCS_SHADOW:beta.noael_studies	irritation	1200	mg/kg/day	mouse	-	90 day	irritation	SOURCE_SUBDIR=sccs_o_019; REPORT_TITLE=OPINION ON N,N'-bis-(2-Hydroxyethyl)-2-nitro-p-phenylenediamine COLIPA n° B34; OPINION_NUMBER=SCCS/1228/09; COMMITTEE=Scientific Committee on Consumer Safety (SCCS); REPORT_DATE=12 July 2010; VALUE_TEXT=1200; DOSE=Toxicity The No Observed Adverse Effect Level (NOAEL) for N,N’-bis-(2-hydroxyethyl)-2-nitro-p- phenylenediamine in the 90 day study was considered to be 240 mg/kg/day, based on effects on kidney, which seemed to be the target organ.; EFFECT=ls and/or analytical data were provided. No data on the stability of N,N’-bis-(2-hydroxyethyl)-2-nitro-p- phenylenediamine in typical hair dye formulations has been provided. Toxicity The No Observed Adverse Effect Level (NOAEL) for N,N’-bis-(2-hydroxyethyl)-2-nitro-p- phenylenediamine in the 90 day study was considered to be 240 mg/kg/day, based on effects on kidney, which seemed to be the target organ. Since no maternal toxicity, foetal toxicity or teratogenicity was seen, the No Observed Adverse Effect Level (NOAEL) for N,N’-bis-(2-hydroxyethyl)-2-nitro-p-phenylenediamine for these endpoints was considered to be 1200 mg/kg/day. No two generation reproduction study was submitted. Skin/eye irritation and sensitisation Neat N,N’-bis-(2-hydroxyethyl)-2-nitro-p-phenylenediamine was not irritant when applied to rabbit skin. However, it was noted that 10% N,N’-bis-(2-hydroxyethyl)-2-nitro-p- phenylenediamine in acetone:olive oil was slightly irritant to the mouse ear in the LLNA test. It was irritant to rabbit eyes. N,N’-bis-(2-h; CITATION_NUMBERS=[]; DETAILS_JSON={"cas_number":"84041-77-0","citation":"","dose":"Toxicity The No Observed Adverse Effect Level (NOAEL) for N,N’-bis-(2-hydroxyethyl)-2-nitro-p- phenylenediamine in the 90 day study was considered to be 240 mg/kg/day, based on effects on kidney, which seemed to be the target organ.","duration":"90 day","effect":"ls and/or analytical data were provided. No data on the stability of N,N’-bis-(2-hydroxyethyl)-2-nitro-p- phenylenediamine in typical hair dye formulations has been provided. Toxicity The No Observed Adverse Effect Level (NOAEL) for N,N’-bis-(2-hydroxyethyl)-2-nitro-p- phenylenediamine in the 90 day study was considered to be 240 mg/kg/day, based on effects on kidney, which seemed to be the target organ. Since no maternal toxicity, foetal toxicity or teratogenicity was seen, the No Observed Adverse Effect Level (NOAEL) for N,N’-bis-(2-hydroxyethyl)-2-nitro-p-phenylenediamine for these endpoints was considered to be 1200 mg/kg/day. No two generation reproduction study was submitted. Skin/eye irritation and sensitisation Neat N,N’-bis-(2-hydroxyethyl)-2-nitro-p-phenylenediamine was not irritant when applied to rabbit skin. However, it was noted that 10% N,N’-bis-(2-hydroxyethyl)-2-nitro-p- phenylenediamine in acetone:olive oil was slightly irritant to the mouse ear in the LLNA test. It was irritant to rabbit eyes. N,N’-bis-(2-h","endpoint":"irritation","ingredient":"N,N'-bis-(2-Hydroxyethyl)-2-nitro-p-phenylenediamine","loael_value":"","noael_unit":"mg/kg/day","noael_value":"1200","page":28,"route":"","species":"mouse","study_id":"sccs_o_019_noael_007"}
UnifiedCodex:SCCS_SHADOW:beta.noael_studies	irritation	240	mg/kg bw/day	-	-	90 day	irritation	SOURCE_SUBDIR=sccs_o_096; REPORT_TITLE=OPINION ON N,N'-bis-(2-Hydroxyethyl)-2-nitro-p-phenylenediamine COLIPA n° B34; OPINION_NUMBER=SCCS/1463/12; COMMITTEE=Scientific Committee on Consumer Safety (SCCS); REPORT_DATE=18 September 2012; VALUE_TEXT=240; DOSE=The No Observed Adverse Effect Level (NOAEL) for N,N’-bis-(2-hydroxyethyl)-2-nitro-p- phenylenediamine in the 90 day study was considered to be 240 mg/kg bw/day, based on effects on kidney and urea at 720 mg/kg bw/day, which seemed to be the target organ.; EFFECT=SCCS/1463/12 Opinion on N,N'-bis-(2-Hydroxyethyl)-2-nitro-p-phenylenediamine ___________________________________________________________________________________________ 35 Toxicity No mortalities occurred up to 5 g/kg bw, so N,N’-bis-(2-hydroxyethyl)-2-nitro-p- phenylenediamine showed no acute toxicity. The No Observed Adverse Effect Level (NOAEL) for N,N’-bis-(2-hydroxyethyl)-2-nitro-p- phenylenediamine in the 90 day study was considered to be 240 mg/kg bw/day, based on effects on kidney and urea at 720 mg/kg bw/day, which seemed to be the target organ. Since no maternal toxicity, foetal toxicity or teratogenicity was seen, the No Observed Adverse Effect Level (NOAEL) for N,N’-bis-(2-hydroxyethyl)-2-nitro-p-phenylenediamine for these endpoints was considered to be 1200 mg/kg/day. Skin/eye irritation and sensitisation Neat N,N’-bis-(2-hydroxyethyl; CITATION_NUMBERS=[]; DETAILS_JSON={"cas_number":"84041-77-0","citation":"","dose":"The No Observed Adverse Effect Level (NOAEL) for N,N’-bis-(2-hydroxyethyl)-2-nitro-p- phenylenediamine in the 90 day study was considered to be 240 mg/kg bw/day, based on effects on kidney and urea at 720 mg/kg bw/day, which seemed to be the target organ.","duration":"90 day","effect":"SCCS/1463/12 Opinion on N,N'-bis-(2-Hydroxyethyl)-2-nitro-p-phenylenediamine ___________________________________________________________________________________________ 35 Toxicity No mortalities occurred up to 5 g/kg bw, so N,N’-bis-(2-hydroxyethyl)-2-nitro-p- phenylenediamine showed no acute toxicity. The No Observed Adverse Effect Level (NOAEL) for N,N’-bis-(2-hydroxyethyl)-2-nitro-p- phenylenediamine in the 90 day study was considered to be 240 mg/kg bw/day, based on effects on kidney and urea at 720 mg/kg bw/day, which seemed to be the target organ. Since no maternal toxicity, foetal toxicity or teratogenicity was seen, the No Observed Adverse Effect Level (NOAEL) for N,N’-bis-(2-hydroxyethyl)-2-nitro-p-phenylenediamine for these endpoints was considered to be 1200 mg/kg/day. Skin/eye irritation and sensitisation Neat N,N’-bis-(2-hydroxyethyl","endpoint":"irritation","ingredient":"N,N'-bis-(2-Hydroxyethyl)-2-nitro-p-phenylenediamine","loael_value":"","noael_unit":"mg/kg bw/day","noael_value":"240","page":35,"route":"","species":"","study_id":"sccs_o_096_noael_010"}
UnifiedCodex:SCCS_SHADOW:beta.noael_studies	irritation	720	mg/kg bw/day	mouse	-	90 day	irritation	SOURCE_SUBDIR=sccs_o_096; REPORT_TITLE=OPINION ON N,N'-bis-(2-Hydroxyethyl)-2-nitro-p-phenylenediamine COLIPA n° B34; OPINION_NUMBER=SCCS/1463/12; COMMITTEE=Scientific Committee on Consumer Safety (SCCS); REPORT_DATE=18 September 2012; VALUE_TEXT=720; DOSE=The No Observed Adverse Effect Level (NOAEL) for N,N’-bis-(2-hydroxyethyl)-2-nitro-p- phenylenediamine in the 90 day study was considered to be 240 mg/kg bw/day, based on effects on kidney and urea at 720 mg/kg bw/day, which seemed to be the target organ.; EFFECT=________________________________________________ 35 Toxicity No mortalities occurred up to 5 g/kg bw, so N,N’-bis-(2-hydroxyethyl)-2-nitro-p- phenylenediamine showed no acute toxicity. The No Observed Adverse Effect Level (NOAEL) for N,N’-bis-(2-hydroxyethyl)-2-nitro-p- phenylenediamine in the 90 day study was considered to be 240 mg/kg bw/day, based on effects on kidney and urea at 720 mg/kg bw/day, which seemed to be the target organ. Since no maternal toxicity, foetal toxicity or teratogenicity was seen, the No Observed Adverse Effect Level (NOAEL) for N,N’-bis-(2-hydroxyethyl)-2-nitro-p-phenylenediamine for these endpoints was considered to be 1200 mg/kg/day. Skin/eye irritation and sensitisation Neat N,N’-bis-(2-hydroxyethyl)-2-nitro-p-phenylenediamine was not irritant when applied to rabbit skin. However, it was noted that 10% N,N’-bis-(2-hydroxyethyl)-2-nitro-p- phenylenediamine in acetone:olive oil was slightly irritant to the mouse ear in the LLNA test. It was irritant to rabbit eyes. N,N’-bis-(2-hydroxyethyl)-2-nitro-p-phenylenediamine was n; CITATION_NUMBERS=[]; DETAILS_JSON={"cas_number":"84041-77-0","citation":"","dose":"The No Observed Adverse Effect Level (NOAEL) for N,N’-bis-(2-hydroxyethyl)-2-nitro-p- phenylenediamine in the 90 day study was considered to be 240 mg/kg bw/day, based on effects on kidney and urea at 720 mg/kg bw/day, which seemed to be the target organ.","duration":"90 day","effect":"________________________________________________ 35 Toxicity No mortalities occurred up to 5 g/kg bw, so N,N’-bis-(2-hydroxyethyl)-2-nitro-p- phenylenediamine showed no acute toxicity. The No Observed Adverse Effect Level (NOAEL) for N,N’-bis-(2-hydroxyethyl)-2-nitro-p- phenylenediamine in the 90 day study was considered to be 240 mg/kg bw/day, based on effects on kidney and urea at 720 mg/kg bw/day, which seemed to be the target organ. Since no maternal toxicity, foetal toxicity or teratogenicity was seen, the No Observed Adverse Effect Level (NOAEL) for N,N’-bis-(2-hydroxyethyl)-2-nitro-p-phenylenediamine for these endpoints was considered to be 1200 mg/kg/day. Skin/eye irritation and sensitisation Neat N,N’-bis-(2-hydroxyethyl)-2-nitro-p-phenylenediamine was not irritant when applied to rabbit skin. However, it was noted that 10% N,N’-bis-(2-hydroxyethyl)-2-nitro-p- phenylenediamine in acetone:olive oil was slightly irritant to the mouse ear in the LLNA test. It was irritant to rabbit eyes. N,N’-bis-(2-hydroxyethyl)-2-nitro-p-phenylenediamine was n","endpoint":"irritation","ingredient":"N,N'-bis-(2-Hydroxyethyl)-2-nitro-p-phenylenediamine","loael_value":"","noael_unit":"mg/kg bw/day","noael_value":"720","page":35,"route":"","species":"mouse","study_id":"sccs_o_096_noael_011"}
UnifiedCodex:SCCS_SHADOW:beta.noael_studies	irritation	1200	mg/kg/day	mouse	-	90 day	irritation	SOURCE_SUBDIR=sccs_o_096; REPORT_TITLE=OPINION ON N,N'-bis-(2-Hydroxyethyl)-2-nitro-p-phenylenediamine COLIPA n° B34; OPINION_NUMBER=SCCS/1463/12; COMMITTEE=Scientific Committee on Consumer Safety (SCCS); REPORT_DATE=18 September 2012; VALUE_TEXT=1200; DOSE=The No Observed Adverse Effect Level (NOAEL) for N,N’-bis-(2-hydroxyethyl)-2-nitro-p- phenylenediamine in the 90 day study was considered to be 240 mg/kg bw/day, based on effects on kidney and urea at 720 mg/kg bw/day, which seemed to be the target organ.; EFFECT=______________ 35 Toxicity No mortalities occurred up to 5 g/kg bw, so N,N’-bis-(2-hydroxyethyl)-2-nitro-p- phenylenediamine showed no acute toxicity. The No Observed Adverse Effect Level (NOAEL) for N,N’-bis-(2-hydroxyethyl)-2-nitro-p- phenylenediamine in the 90 day study was considered to be 240 mg/kg bw/day, based on effects on kidney and urea at 720 mg/kg bw/day, which seemed to be the target organ. Since no maternal toxicity, foetal toxicity or teratogenicity was seen, the No Observed Adverse Effect Level (NOAEL) for N,N’-bis-(2-hydroxyethyl)-2-nitro-p-phenylenediamine for these endpoints was considered to be 1200 mg/kg/day. Skin/eye irritation and sensitisation Neat N,N’-bis-(2-hydroxyethyl)-2-nitro-p-phenylenediamine was not irritant when applied to rabbit skin. However, it was noted that 10% N,N’-bis-(2-hydroxyethyl)-2-nitro-p- phenylenediamine in acetone:olive oil was slightly irritant to the mouse ear in the LLNA test. It was irritant to rabbit eyes. N,N’-bis-(2-hydroxyethyl)-2-nitro-p-phenylenediamine was not dete; CITATION_NUMBERS=[]; DETAILS_JSON={"cas_number":"84041-77-0","citation":"","dose":"The No Observed Adverse Effect Level (NOAEL) for N,N’-bis-(2-hydroxyethyl)-2-nitro-p- phenylenediamine in the 90 day study was considered to be 240 mg/kg bw/day, based on effects on kidney and urea at 720 mg/kg bw/day, which seemed to be the target organ.","duration":"90 day","effect":"______________ 35 Toxicity No mortalities occurred up to 5 g/kg bw, so N,N’-bis-(2-hydroxyethyl)-2-nitro-p- phenylenediamine showed no acute toxicity. The No Observed Adverse Effect Level (NOAEL) for N,N’-bis-(2-hydroxyethyl)-2-nitro-p- phenylenediamine in the 90 day study was considered to be 240 mg/kg bw/day, based on effects on kidney and urea at 720 mg/kg bw/day, which seemed to be the target organ. Since no maternal toxicity, foetal toxicity or teratogenicity was seen, the No Observed Adverse Effect Level (NOAEL) for N,N’-bis-(2-hydroxyethyl)-2-nitro-p-phenylenediamine for these endpoints was considered to be 1200 mg/kg/day. Skin/eye irritation and sensitisation Neat N,N’-bis-(2-hydroxyethyl)-2-nitro-p-phenylenediamine was not irritant when applied to rabbit skin. However, it was noted that 10% N,N’-bis-(2-hydroxyethyl)-2-nitro-p- phenylenediamine in acetone:olive oil was slightly irritant to the mouse ear in the LLNA test. It was irritant to rabbit eyes. N,N’-bis-(2-hydroxyethyl)-2-nitro-p-phenylenediamine was not dete","endpoint":"irritation","ingredient":"N,N'-bis-(2-Hydroxyethyl)-2-nitro-p-phenylenediamine","loael_value":"","noael_unit":"mg/kg/day","noael_value":"1200","page":35,"route":"","species":"mouse","study_id":"sccs_o_096_noael_012"}
UnifiedCodex:SCCS_SHADOW:beta.noael_studies	irritation	240	mg/kg bw/day	-	-	90-day	irritation	SOURCE_SUBDIR=sccs_o_196; REPORT_TITLE=OPINION ON N,N'-Bis-(2-hydroxyethyl)-2-nitro-p-phenylenediamine (B34); OPINION_NUMBER=SCCS/1572/16; COMMITTEE=Scientific Committee on Consumer Safety (SCCS); REPORT_DATE=Final version of 16 September 2016; VALUE_TEXT=240; DOSE=The No Observed Adverse Effect Level (NOAEL) for N,N’-bis-(2-hydroxyethyl)-2-nitro-p- phenylenediamine in the 90-day study was considered to be 240 mg/kg bw/day, based on the effects on the kidney at 720 mg/kg bw/d, which seemed to be the target organ.; EFFECT=SCCS-rejected applicant NOAEL: d and the result. No analytical details and/or analytical data were provided. The applicant provided a simple UV method to evaluate stability in an oxidative hair coloration product. Stability testing using a simple comparison of UV spectra is not acceptable. A more selective analytical method such as HPLC with PDA detection should be used to evaluate stability for up to 60 min. Toxicity No mortalities occurred up to 5g/kg bw, so N,N’-bis-(2-hydroxyethyl)-2-nitro-p- phenylenediamine showed no acute toxicity. The No Observed Adverse Effect Level (NOAEL) for N,N’-bis-(2-hydroxyethyl)-2-nitro-p- phenylenediamine in the 90-day study was considered to be 240 mg/kg bw/day, based on the effects on the kidney at 720 mg/kg bw/d, which seemed to be the target organ. Since no maternal toxicity, foetal toxicity or teratogenicity was seen, the No Observed Adverse Effect Level (NOAEL) for N,N’-bis-(2-hydroxyethyl)-2-nitro-p-phenylenediamine for these endpoints was considered to be 1200 mg/kg bw/d. Skin/eye irritation and sensitisation Neat N,N’-bis-(2-hydroxyethyl)-; CITATION_NUMBERS=[]; DETAILS_JSON={"cas_number":"84041-77-0","citation":"","dose":"The No Observed Adverse Effect Level (NOAEL) for N,N’-bis-(2-hydroxyethyl)-2-nitro-p- phenylenediamine in the 90-day study was considered to be 240 mg/kg bw/day, based on the effects on the kidney at 720 mg/kg bw/d, which seemed to be the target organ.","duration":"90-day","effect":"SCCS-rejected applicant NOAEL: d and the result. No analytical details and/or analytical data were provided. The applicant provided a simple UV method to evaluate stability in an oxidative hair coloration product. Stability testing using a simple comparison of UV spectra is not acceptable. A more selective analytical method such as HPLC with PDA detection should be used to evaluate stability for up to 60 min. Toxicity No mortalities occurred up to 5g/kg bw, so N,N’-bis-(2-hydroxyethyl)-2-nitro-p- phenylenediamine showed no acute toxicity. The No Observed Adverse Effect Level (NOAEL) for N,N’-bis-(2-hydroxyethyl)-2-nitro-p- phenylenediamine in the 90-day study was considered to be 240 mg/kg bw/day, based on the effects on the kidney at 720 mg/kg bw/d, which seemed to be the target organ. Since no maternal toxicity, foetal toxicity or teratogenicity was seen, the No Observed Adverse Effect Level (NOAEL) for N,N’-bis-(2-hydroxyethyl)-2-nitro-p-phenylenediamine for these endpoints was considered to be 1200 mg/kg bw/d. Skin/eye irritation and sensitisation Neat N,N’-bis-(2-hydroxyethyl)-","endpoint":"irritation","ingredient":"N,N'-bis-(2-Hydroxyethyl)-2-nitro-p-phenylenediamine","loael_value":"","noael_unit":"mg/kg bw/day","noael_value":"240","page":37,"route":"","species":"","study_id":"sccs_o_196_noael_016"}
UnifiedCodex:SCCS_SHADOW:beta.noael_studies	irritation	240	mg/kg bw/day	-	-	90-day	irritation	SOURCE_SUBDIR=sccs_o_196; REPORT_TITLE=OPINION ON N,N'-Bis-(2-hydroxyethyl)-2-nitro-p-phenylenediamine (B34); OPINION_NUMBER=SCCS/1572/16; COMMITTEE=Scientific Committee on Consumer Safety (SCCS); REPORT_DATE=Final version of 16 September 2016; VALUE_TEXT=240; DOSE=The No Observed Adverse Effect Level (NOAEL) for N,N’-bis-(2-hydroxyethyl)-2-nitro-p- phenylenediamine in the 90-day study was considered to be 240 mg/kg bw/day, based on the effects on the kidney at 720 mg/kg bw/d, which seemed to be the target organ.; EFFECT=SCCS-rejected applicant NOAEL: tails and/or analytical data were provided. The applicant provided a simple UV method to evaluate stability in an oxidative hair coloration product. Stability testing using a simple comparison of UV spectra is not acceptable. A more selective analytical method such as HPLC with PDA detection should be used to evaluate stability for up to 60 min. Toxicity No mortalities occurred up to 5g/kg bw, so N,N’-bis-(2-hydroxyethyl)-2-nitro-p- phenylenediamine showed no acute toxicity. The No Observed Adverse Effect Level (NOAEL) for N,N’-bis-(2-hydroxyethyl)-2-nitro-p- phenylenediamine in the 90-day study was considered to be 240 mg/kg bw/day, based on the effects on the kidney at 720 mg/kg bw/d, which seemed to be the target organ. Since no maternal toxicity, foetal toxicity or teratogenicity was seen, the No Observed Adverse Effect Level (NOAEL) for N,N’-bis-(2-hydroxyethyl)-2-nitro-p-phenylenediamine for these endpoints was considered to be 1200 mg/kg bw/d. Skin/eye irritation and sensitisation Neat N,N’-bis-(2-hydroxyethyl)-2-nitro; CITATION_NUMBERS=[]; DETAILS_JSON={"cas_number":"84041-77-0","citation":"","dose":"The No Observed Adverse Effect Level (NOAEL) for N,N’-bis-(2-hydroxyethyl)-2-nitro-p- phenylenediamine in the 90-day study was considered to be 240 mg/kg bw/day, based on the effects on the kidney at 720 mg/kg bw/d, which seemed to be the target organ.","duration":"90-day","effect":"SCCS-rejected applicant NOAEL: tails and/or analytical data were provided. The applicant provided a simple UV method to evaluate stability in an oxidative hair coloration product. Stability testing using a simple comparison of UV spectra is not acceptable. A more selective analytical method such as HPLC with PDA detection should be used to evaluate stability for up to 60 min. Toxicity No mortalities occurred up to 5g/kg bw, so N,N’-bis-(2-hydroxyethyl)-2-nitro-p- phenylenediamine showed no acute toxicity. The No Observed Adverse Effect Level (NOAEL) for N,N’-bis-(2-hydroxyethyl)-2-nitro-p- phenylenediamine in the 90-day study was considered to be 240 mg/kg bw/day, based on the effects on the kidney at 720 mg/kg bw/d, which seemed to be the target organ. Since no maternal toxicity, foetal toxicity or teratogenicity was seen, the No Observed Adverse Effect Level (NOAEL) for N,N’-bis-(2-hydroxyethyl)-2-nitro-p-phenylenediamine for these endpoints was considered to be 1200 mg/kg bw/d. Skin/eye irritation and sensitisation Neat N,N’-bis-(2-hydroxyethyl)-2-nitro","endpoint":"irritation","ingredient":"N,N'-bis-(2-Hydroxyethyl)-2-nitro-p-phenylenediamine","loael_value":"","noael_unit":"mg/kg bw/day","noael_value":"240","page":37,"route":"","species":"","study_id":"sccs_o_196_noael_017"}
UnifiedCodex:SCCS_SHADOW:beta.noael_studies	irritation	720	mg/kg bw/d	mouse	-	90-day	irritation	SOURCE_SUBDIR=sccs_o_196; REPORT_TITLE=OPINION ON N,N'-Bis-(2-hydroxyethyl)-2-nitro-p-phenylenediamine (B34); OPINION_NUMBER=SCCS/1572/16; COMMITTEE=Scientific Committee on Consumer Safety (SCCS); REPORT_DATE=Final version of 16 September 2016; VALUE_TEXT=720; DOSE=The No Observed Adverse Effect Level (NOAEL) for N,N’-bis-(2-hydroxyethyl)-2-nitro-p- phenylenediamine in the 90-day study was considered to be 240 mg/kg bw/day, based on the effects on the kidney at 720 mg/kg bw/d, which seemed to be the target organ.; EFFECT=n should be used to evaluate stability for up to 60 min. Toxicity No mortalities occurred up to 5g/kg bw, so N,N’-bis-(2-hydroxyethyl)-2-nitro-p- phenylenediamine showed no acute toxicity. The No Observed Adverse Effect Level (NOAEL) for N,N’-bis-(2-hydroxyethyl)-2-nitro-p- phenylenediamine in the 90-day study was considered to be 240 mg/kg bw/day, based on the effects on the kidney at 720 mg/kg bw/d, which seemed to be the target organ. Since no maternal toxicity, foetal toxicity or teratogenicity was seen, the No Observed Adverse Effect Level (NOAEL) for N,N’-bis-(2-hydroxyethyl)-2-nitro-p-phenylenediamine for these endpoints was considered to be 1200 mg/kg bw/d. Skin/eye irritation and sensitisation Neat N,N’-bis-(2-hydroxyethyl)-2-nitro-p-phenylenediamine was not irritant when applied to rabbit skin. However, it was noted that 10% N,N’-bis-(2-hydroxyethyl)-2-nitro-p- phenylenediamine in acetone:olive oil was slightly irritant to the mouse ear in the LLNA test. It was irritant to rabbit eyes. N,N’-bis-(2-hydroxyethyl)-2-nitro-p-phenylenediamine was; CITATION_NUMBERS=[]; DETAILS_JSON={"cas_number":"84041-77-0","citation":"","dose":"The No Observed Adverse Effect Level (NOAEL) for N,N’-bis-(2-hydroxyethyl)-2-nitro-p- phenylenediamine in the 90-day study was considered to be 240 mg/kg bw/day, based on the effects on the kidney at 720 mg/kg bw/d, which seemed to be the target organ.","duration":"90-day","effect":"n should be used to evaluate stability for up to 60 min. Toxicity No mortalities occurred up to 5g/kg bw, so N,N’-bis-(2-hydroxyethyl)-2-nitro-p- phenylenediamine showed no acute toxicity. The No Observed Adverse Effect Level (NOAEL) for N,N’-bis-(2-hydroxyethyl)-2-nitro-p- phenylenediamine in the 90-day study was considered to be 240 mg/kg bw/day, based on the effects on the kidney at 720 mg/kg bw/d, which seemed to be the target organ. Since no maternal toxicity, foetal toxicity or teratogenicity was seen, the No Observed Adverse Effect Level (NOAEL) for N,N’-bis-(2-hydroxyethyl)-2-nitro-p-phenylenediamine for these endpoints was considered to be 1200 mg/kg bw/d. Skin/eye irritation and sensitisation Neat N,N’-bis-(2-hydroxyethyl)-2-nitro-p-phenylenediamine was not irritant when applied to rabbit skin. However, it was noted that 10% N,N’-bis-(2-hydroxyethyl)-2-nitro-p- phenylenediamine in acetone:olive oil was slightly irritant to the mouse ear in the LLNA test. It was irritant to rabbit eyes. N,N’-bis-(2-hydroxyethyl)-2-nitro-p-phenylenediamine was","endpoint":"irritation","ingredient":"N,N'-bis-(2-Hydroxyethyl)-2-nitro-p-phenylenediamine","loael_value":"","noael_unit":"mg/kg bw/d","noael_value":"720","page":37,"route":"","species":"mouse","study_id":"sccs_o_196_noael_018"}
UnifiedCodex:SCCS_SHADOW:beta.noael_studies	irritation	1200	mg/kg bw/d	mouse	-	90-day	irritation	SOURCE_SUBDIR=sccs_o_196; REPORT_TITLE=OPINION ON N,N'-Bis-(2-hydroxyethyl)-2-nitro-p-phenylenediamine (B34); OPINION_NUMBER=SCCS/1572/16; COMMITTEE=Scientific Committee on Consumer Safety (SCCS); REPORT_DATE=Final version of 16 September 2016; VALUE_TEXT=1200; DOSE=The No Observed Adverse Effect Level (NOAEL) for N,N’-bis-(2-hydroxyethyl)-2-nitro-p- phenylenediamine in the 90-day study was considered to be 240 mg/kg bw/day, based on the effects on the kidney at 720 mg/kg bw/d, which seemed to be the target organ.; EFFECT=lity for up to 60 min. Toxicity No mortalities occurred up to 5g/kg bw, so N,N’-bis-(2-hydroxyethyl)-2-nitro-p- phenylenediamine showed no acute toxicity. The No Observed Adverse Effect Level (NOAEL) for N,N’-bis-(2-hydroxyethyl)-2-nitro-p- phenylenediamine in the 90-day study was considered to be 240 mg/kg bw/day, based on the effects on the kidney at 720 mg/kg bw/d, which seemed to be the target organ. Since no maternal toxicity, foetal toxicity or teratogenicity was seen, the No Observed Adverse Effect Level (NOAEL) for N,N’-bis-(2-hydroxyethyl)-2-nitro-p-phenylenediamine for these endpoints was considered to be 1200 mg/kg bw/d. Skin/eye irritation and sensitisation Neat N,N’-bis-(2-hydroxyethyl)-2-nitro-p-phenylenediamine was not irritant when applied to rabbit skin. However, it was noted that 10% N,N’-bis-(2-hydroxyethyl)-2-nitro-p- phenylenediamine in acetone:olive oil was slightly irritant to the mouse ear in the LLNA test. It was irritant to rabbit eyes. N,N’-bis-(2-hydroxyethyl)-2-nitro-p-phenylenediamine was not det; CITATION_NUMBERS=[]; DETAILS_JSON={"cas_number":"84041-77-0","citation":"","dose":"The No Observed Adverse Effect Level (NOAEL) for N,N’-bis-(2-hydroxyethyl)-2-nitro-p- phenylenediamine in the 90-day study was considered to be 240 mg/kg bw/day, based on the effects on the kidney at 720 mg/kg bw/d, which seemed to be the target organ.","duration":"90-day","effect":"lity for up to 60 min. Toxicity No mortalities occurred up to 5g/kg bw, so N,N’-bis-(2-hydroxyethyl)-2-nitro-p- phenylenediamine showed no acute toxicity. The No Observed Adverse Effect Level (NOAEL) for N,N’-bis-(2-hydroxyethyl)-2-nitro-p- phenylenediamine in the 90-day study was considered to be 240 mg/kg bw/day, based on the effects on the kidney at 720 mg/kg bw/d, which seemed to be the target organ. Since no maternal toxicity, foetal toxicity or teratogenicity was seen, the No Observed Adverse Effect Level (NOAEL) for N,N’-bis-(2-hydroxyethyl)-2-nitro-p-phenylenediamine for these endpoints was considered to be 1200 mg/kg bw/d. Skin/eye irritation and sensitisation Neat N,N’-bis-(2-hydroxyethyl)-2-nitro-p-phenylenediamine was not irritant when applied to rabbit skin. However, it was noted that 10% N,N’-bis-(2-hydroxyethyl)-2-nitro-p- phenylenediamine in acetone:olive oil was slightly irritant to the mouse ear in the LLNA test. It was irritant to rabbit eyes. N,N’-bis-(2-hydroxyethyl)-2-nitro-p-phenylenediamine was not det","endpoint":"irritation","ingredient":"N,N'-bis-(2-Hydroxyethyl)-2-nitro-p-phenylenediamine","loael_value":"","noael_unit":"mg/kg bw/d","noael_value":"1200","page":37,"route":"","species":"mouse","study_id":"sccs_o_196_noael_019"}

openFDA substances 4 endpoints

Source	Endpoint Type	Value	Unit	Species	Route	Duration	Study Type	Reference
openFDA substances	FDA UNII substance identifier	3X0E669O5S	UNII	-	-	-	chemical	{"approval_status":null,"molecular_formula":"C10H15N3O4","source_table":"substance_identifiers_fda","substance_class":"chemical","unii_code":"3X0E669O5S"}
openFDA substances	FDA UNII substance identifier	3X0E669O5S	UNII	-	-	-	chemical	{"approval_status":null,"molecular_formula":"C10H15N3O4","source_table":"substance_identifiers_fda","substance_class":"chemical","unii_code":"3X0E669O5S"}
openFDA substances	FDA UNII substance identifier	3X0E669O5S	UNII	-	-	-	chemical	{"approval_status":null,"molecular_formula":"C10H15N3O4","source_table":"substance_identifiers_fda","substance_class":"chemical","unii_code":"3X0E669O5S"}
openFDA substances	FDA UNII substance identifier	3X0E669O5S	UNII	-	-	-	chemical	{"approval_status":null,"molecular_formula":"C10H15N3O4","source_table":"substance_identifiers_fda","substance_class":"chemical","unii_code":"3X0E669O5S"}