NOAEL Studies
Cosmetic Ingredient
4-Nitro-O-Phenylenediamine NOAEL Studies
INCI: 4-NITRO-O-PHENYLENEDIAMINE
CAS: 99-56-9
Raw No Observed Adverse Effect Level endpoint records grouped by source. This page does not render calculated Margin of Safety values.
CIR Safety Assessment 8 endpoints
| Source | Endpoint Type | Value | Unit | Species | Route | Duration | Study Type | Reference |
|---|---|---|---|---|---|---|---|---|
| CIR Safety Assessment | NOAEL | =15 | mg/kg bw/d | rat | dermal | Chronic | NOAEL study | {"citation":"10); (5; 45","dose":"/10) and females (5/10) of the highest dose group.","effect":"/10) and females (5/10) of the highest dose group. At the other dose levels, only minimal to slight hepatocellular hypertrophy was observed. Minimal hepatocellular hypertrophy persisted after recovery in treated males of all dose levels, whereas females reverted completely. After recovery, changes in the thyroid glands of treated male rats were reversible when compared with control males. The no-observed-adverse-effect level (NOAEL) was determined to be 45 mg/kg bw/d by the researchers, but the SCCP considered the NOAEL to be 15 mg/kg bw/d based on hepatocellular hypertrophy in males of all dose levels.6 Chronic Toxicity Studies Dermal A semi-permanent colorant shampoo containing 4-Nitro-o-Phenylenediamine (unspecified concentration) was applied to the skin of strain A and strain DBAf mice 2 times/wk for 80 wk.2 Toxic effects were seen in the DBAf strain: obstructing crystals were seen in the urinary bladder and on the penile skin. The urinary bladder, seminal vesicles, and stomachs were distended, the renal tubules were dilated, and a few mice had chronic gastritis. In another st...","page":6,"pdf":"fr925.pdf","row_type":"noael_study","study_id":"fr925_noael_002"} |
| CIR Safety Assessment | NOAEL | =15 | mg/kg bw/d | rat | dermal | Chronic | NOAEL study | {"citation":"10); (5; 45","dose":"/10) and females (5/10) of the highest dose group.","effect":"/10) and females (5/10) of the highest dose group. At the other dose levels, only minimal to slight hepatocellular hypertrophy was observed. Minimal hepatocellular hypertrophy persisted after recovery in treated males of all dose levels, whereas females reverted completely. After recovery, changes in the thyroid glands of treated male rats were reversible when compared with control males. The no-observed-adverse-effect level (NOAEL) was determined to be 45 mg/kg bw/d by the researchers, but the SCCP considered the NOAEL to be 15 mg/kg bw/d based on hepatocellular hypertrophy in males of all dose levels.6 Chronic Toxicity Studies Dermal A semi-permanent colorant shampoo containing 4-Nitro-o-Phenylenediamine (unspecified concentration) was applied to the skin of strain A and strain DBAf mice 2 times/wk for 80 wk.2 Toxic effects were seen in the DBAf strain: obstructing crystals were seen in the urinary bladder and on the penile skin. The urinary bladder, seminal vesicles, and stomachs were distended, the renal tubules were dilated, and a few mice had chronic gastritis. In another st...","page":6,"pdf":"fr925.pdf","row_type":"noael_study","study_id":"fr925_noael_002"} |
| CIR Safety Assessment | NOAEL | =15 | mg/kg bw/d | rat | dermal | Chronic | NOAEL study | {"citation":"10); (5; 45","dose":"/10) and females (5/10) of the highest dose group.","effect":"/10) and females (5/10) of the highest dose group. At the other dose levels, only minimal to slight hepatocellular hypertrophy was observed. Minimal hepatocellular hypertrophy persisted after recovery in treated males of all dose levels, whereas females reverted completely. After recovery, changes in the thyroid glands of treated male rats were reversible when compared with control males. The no-observed-adverse-effect level (NOAEL) was determined to be 45 mg/kg bw/d by the researchers, but the SCCP considered the NOAEL to be 15 mg/kg bw/d based on hepatocellular hypertrophy in males of all dose levels.6 Chronic Toxicity Studies Dermal A semi-permanent colorant shampoo containing 4-Nitro-o-Phenylenediamine (unspecified concentration) was applied to the skin of strain A and strain DBAf mice 2 times/wk for 80 wk.2 Toxic effects were seen in the DBAf strain: obstructing crystals were seen in the urinary bladder and on the penile skin. The urinary bladder, seminal vesicles, and stomachs were distended, the renal tubules were dilated, and a few mice had chronic gastritis. In another st...","page":6,"pdf":"fr925.pdf","row_type":"noael_study","study_id":"fr925_noael_002"} |
| CIR Safety Assessment | NOAEL | =15 | mg/kg bw/d | rat | dermal | Chronic | NOAEL study | {"citation":"10); (5; 45","dose":"/10) and females (5/10) of the highest dose group.","effect":"/10) and females (5/10) of the highest dose group. At the other dose levels, only minimal to slight hepatocellular hypertrophy was observed. Minimal hepatocellular hypertrophy persisted after recovery in treated males of all dose levels, whereas females reverted completely. After recovery, changes in the thyroid glands of treated male rats were reversible when compared with control males. The no-observed-adverse-effect level (NOAEL) was determined to be 45 mg/kg bw/d by the researchers, but the SCCP considered the NOAEL to be 15 mg/kg bw/d based on hepatocellular hypertrophy in males of all dose levels.6 Chronic Toxicity Studies Dermal A semi-permanent colorant shampoo containing 4-Nitro-o-Phenylenediamine (unspecified concentration) was applied to the skin of strain A and strain DBAf mice 2 times/wk for 80 wk.2 Toxic effects were seen in the DBAf strain: obstructing crystals were seen in the urinary bladder and on the penile skin. The urinary bladder, seminal vesicles, and stomachs were distended, the renal tubules were dilated, and a few mice had chronic gastritis. In another st...","page":6,"pdf":"fr925.pdf","row_type":"noael_study","study_id":"fr925_noael_002"} |
| CIR Safety Assessment | NOAEL | =45 | mg/kg bw/d | rat | dermal | Chronic | NOAEL study | {"citation":"(8; 10); (5","dose":"Slight to moderate hepatocellular hypertrophy was observed in males (8/10) and females (5/10) of the highest dose group.","effect":"bw/d (increased incidence of follicular hypertrophy). Slight to moderate hepatocellular hypertrophy was observed in males (8/10) and females (5/10) of the highest dose group. At the other dose levels, only minimal to slight hepatocellular hypertrophy was observed. Minimal hepatocellular hypertrophy persisted after recovery in treated males of all dose levels, whereas females reverted completely. After recovery, changes in the thyroid glands of treated male rats were reversible when compared with control males. The no-observed-adverse-effect level (NOAEL) was determined to be 45 mg/kg bw/d by the researchers, but the SCCP considered the NOAEL to be 15 mg/kg bw/d based on hepatocellular hypertrophy in males of all dose levels.6 Chronic Toxicity Studies Dermal A semi-permanent colorant shampoo containing 4-Nitro-o-Phenylenediamine (unspecified concentration) was applied to the skin of strain A and strain DBAf mice 2 times/wk for 80 wk.2 Toxic effects were seen in the DBAf strain: obstructing crystals were seen in the urinary bladder and on the penile skin. The urinary bladder, semina...","page":6,"pdf":"fr925.pdf","row_type":"noael_study","study_id":"fr925_noael_001"} |
| CIR Safety Assessment | NOAEL | =45 | mg/kg bw/d | rat | dermal | Chronic | NOAEL study | {"citation":"(8; 10); (5","dose":"Slight to moderate hepatocellular hypertrophy was observed in males (8/10) and females (5/10) of the highest dose group.","effect":"bw/d (increased incidence of follicular hypertrophy). Slight to moderate hepatocellular hypertrophy was observed in males (8/10) and females (5/10) of the highest dose group. At the other dose levels, only minimal to slight hepatocellular hypertrophy was observed. Minimal hepatocellular hypertrophy persisted after recovery in treated males of all dose levels, whereas females reverted completely. After recovery, changes in the thyroid glands of treated male rats were reversible when compared with control males. The no-observed-adverse-effect level (NOAEL) was determined to be 45 mg/kg bw/d by the researchers, but the SCCP considered the NOAEL to be 15 mg/kg bw/d based on hepatocellular hypertrophy in males of all dose levels.6 Chronic Toxicity Studies Dermal A semi-permanent colorant shampoo containing 4-Nitro-o-Phenylenediamine (unspecified concentration) was applied to the skin of strain A and strain DBAf mice 2 times/wk for 80 wk.2 Toxic effects were seen in the DBAf strain: obstructing crystals were seen in the urinary bladder and on the penile skin. The urinary bladder, semina...","page":6,"pdf":"fr925.pdf","row_type":"noael_study","study_id":"fr925_noael_001"} |
| CIR Safety Assessment | NOAEL | =45 | mg/kg bw/d | rat | dermal | Chronic | NOAEL study | {"citation":"(8; 10); (5","dose":"Slight to moderate hepatocellular hypertrophy was observed in males (8/10) and females (5/10) of the highest dose group.","effect":"bw/d (increased incidence of follicular hypertrophy). Slight to moderate hepatocellular hypertrophy was observed in males (8/10) and females (5/10) of the highest dose group. At the other dose levels, only minimal to slight hepatocellular hypertrophy was observed. Minimal hepatocellular hypertrophy persisted after recovery in treated males of all dose levels, whereas females reverted completely. After recovery, changes in the thyroid glands of treated male rats were reversible when compared with control males. The no-observed-adverse-effect level (NOAEL) was determined to be 45 mg/kg bw/d by the researchers, but the SCCP considered the NOAEL to be 15 mg/kg bw/d based on hepatocellular hypertrophy in males of all dose levels.6 Chronic Toxicity Studies Dermal A semi-permanent colorant shampoo containing 4-Nitro-o-Phenylenediamine (unspecified concentration) was applied to the skin of strain A and strain DBAf mice 2 times/wk for 80 wk.2 Toxic effects were seen in the DBAf strain: obstructing crystals were seen in the urinary bladder and on the penile skin. The urinary bladder, semina...","page":6,"pdf":"fr925.pdf","row_type":"noael_study","study_id":"fr925_noael_001"} |
| CIR Safety Assessment | NOAEL | =45 | mg/kg bw/d | rat | dermal | Chronic | NOAEL study | {"citation":"(8; 10); (5","dose":"Slight to moderate hepatocellular hypertrophy was observed in males (8/10) and females (5/10) of the highest dose group.","effect":"bw/d (increased incidence of follicular hypertrophy). Slight to moderate hepatocellular hypertrophy was observed in males (8/10) and females (5/10) of the highest dose group. At the other dose levels, only minimal to slight hepatocellular hypertrophy was observed. Minimal hepatocellular hypertrophy persisted after recovery in treated males of all dose levels, whereas females reverted completely. After recovery, changes in the thyroid glands of treated male rats were reversible when compared with control males. The no-observed-adverse-effect level (NOAEL) was determined to be 45 mg/kg bw/d by the researchers, but the SCCP considered the NOAEL to be 15 mg/kg bw/d based on hepatocellular hypertrophy in males of all dose levels.6 Chronic Toxicity Studies Dermal A semi-permanent colorant shampoo containing 4-Nitro-o-Phenylenediamine (unspecified concentration) was applied to the skin of strain A and strain DBAf mice 2 times/wk for 80 wk.2 Toxic effects were seen in the DBAf strain: obstructing crystals were seen in the urinary bladder and on the penile skin. The urinary bladder, semina...","page":6,"pdf":"fr925.pdf","row_type":"noael_study","study_id":"fr925_noael_001"} |
IARC Monographs 3 endpoints
| Source | Endpoint Type | Value | Unit | Species | Route | Duration | Study Type | Reference |
|---|---|---|---|---|---|---|---|---|
| IARC Monographs | IARC carcinogenicity classification | 3 | IARC group | - | - | 1987 | IARC Monographs | {"additional_info":"volume_publication_year=1987","evaluation_year":1987,"source_table":"iarc_classifications","volume":"16, Sup 7"} |
| IARC Monographs | IARC carcinogenicity classification | 3 | IARC group | - | - | 1987 | IARC Monographs | {"additional_info":"volume_publication_year=1987","evaluation_year":1987,"source_table":"iarc_classifications","volume":"16, Sup 7"} |
| IARC Monographs | IARC carcinogenicity classification | 3 | IARC group | - | - | 1987 | IARC Monographs | {"additional_info":"volume_publication_year=1987","evaluation_year":1987,"source_table":"iarc_classifications","volume":"16, Sup 7"} |
NTP ICE cancer 3 endpoints
| Source | Endpoint Type | Value | Unit | Species | Route | Duration | Study Type | Reference |
|---|---|---|---|---|---|---|---|---|
| NTP ICE cancer | IARC group | 3 | unitless | - | - | - | WOE; IARC Carcinogenicity | sheet=Data; excel_row=9805; Record_ID=cancer_5434; Data_Type=WOE; Formulation_Name=4-Nitro-1,2-phenylenediamine; Mixture=Chemical; DTXSID=DTXSID9020958; Assay=IARC Carcinogenicity; Endpoint=IARC group; Response=3; Response_Unit=Unitless; URL=http://publications.iarc.fr/34; http://publications.iarc.fr/139; URL_CompTox=https://comptox.epa.gov/dashboard/chemical/details/DTXSID9020958; URL_CEBS=https://doi.org/10.22427/NTP-DATA-DTXSID9020958 |
| NTP ICE cancer | Top dose | 750 | ppm | Rat | - | - | In Vivo; NTP Carcinogenicity | sheet=Data; excel_row=9807; Record_ID=cancer_5435; Data_Type=In Vivo; Formulation_Name=4-Nitro-o-phenylenediamine; Mixture=Chemical; DTXSID=DTXSID9020958; Assay=NTP Carcinogenicity; Endpoint=Top dose; Response=750; Response_Unit=ppm; Species=Rat; Strain=F344/N; Sex=Male; Reference=TR-180; URL=https://ntp.niehs.nih.gov/publications/reports/tr/100s/tr180/index.html; URL_CompTox=https://comptox.epa.gov/dashboard/chemical/details/DTXSID9020958; URL_CEBS=https://doi.org/10.22427/NTP-DATA-DTXSID9020958 |
| NTP ICE cancer | Top dose | 7500 | ppm | Mouse | - | - | In Vivo; NTP Carcinogenicity | sheet=Data; excel_row=9803; Record_ID=cancer_5432; Data_Type=In Vivo; Formulation_Name=4-Nitro-o-phenylenediamine; Mixture=Chemical; DTXSID=DTXSID9020958; Assay=NTP Carcinogenicity; Endpoint=Top dose; Response=7500; Response_Unit=ppm; Species=Mouse; Strain=B6C3F1; Sex=Male; Reference=TR-180; URL=https://ntp.niehs.nih.gov/publications/reports/tr/100s/tr180/index.html; URL_CompTox=https://comptox.epa.gov/dashboard/chemical/details/DTXSID9020958; URL_CEBS=https://doi.org/10.22427/NTP-DATA-DTXSID9020958 |
SCCS Opinion 32 endpoints
| Source | Endpoint Type | Value | Unit | Species | Route | Duration | Study Type | Reference |
|---|---|---|---|---|---|---|---|---|
| SCCS Opinion | NOAEL | =0.042 | mg/kg | rat | oral | 90 day | dermal absorption | {"dose":"Safety evaluation (including calculation of the MoS) CALCULATION OF THE MARGIN OF SAFETY (4-nitro-o-phenylenediamine) (oxidative) Maximum absorption through the skin A (µg/cm2) = 3.6 µg/cm2 Skin Area surface SAS (cm2) = 700 cm2 Dermal absorption per treatment SAS x A x 0.001 = 2.52 mg Typical body weight of human = 60 kg Systemic exposure dose (...","effect":"SCCP/0980/06 OPINION ON 4-NITRO-O-PHENYLENEDIAMINE 55 3.3.13. Safety evaluation (including calculation of the MoS) CALCULATION OF THE MARGIN OF SAFETY (4-nitro-o-phenylenediamine) (oxidative) Maximum absorption through the skin A (µg/cm2) = 3.6 µg/cm2 Skin Area surface SAS (cm2) = 700 cm2 Dermal absorption per treatment SAS x A x 0.001 = 2.52 mg Typical body weight of human = 60 kg Systemic exposure dose (SED) SAS x A x 0.001/60 = 0.042 mg/kg No observed adverse effect level NOAEL = 15 mg/kg (rat, oral, 90 day) Margin of Safety NOAEL / SED = 357 3.3.14. Discussion Physico-chemical specifications 4-nitro-o-phenylenediamine is used in oxidative hair dye formulations at a maximum concentration of 0.5%, after mixing with hydrogen peroxide. Stability of 4-nitro-o- phenylenediamine in marketed products is not reported. General toxicity The acute median lethal oral dose of 4-nitro-o-phenylenediamine reported in mice and rats varies from 680 to 2100 mg/kg bw. The majority of the toxico","page":55,"pdf":"sccp_o_093.pdf","row_type":"noael_study","study_id":"sccp_o_093_noael_008"} |
| SCCS Opinion | NOAEL | =0.042 | mg/kg | rat | oral | 90 day | dermal absorption | {"dose":"Safety evaluation (including calculation of the MoS) CALCULATION OF THE MARGIN OF SAFETY (4-nitro-o-phenylenediamine) (oxidative) Maximum absorption through the skin A (µg/cm2) = 3.6 µg/cm2 Skin Area surface SAS (cm2) = 700 cm2 Dermal absorption per treatment SAS x A x 0.001 = 2.52 mg Typical body weight of human = 60 kg Systemic exposure dose (...","effect":"SCCP/0980/06 OPINION ON 4-NITRO-O-PHENYLENEDIAMINE 55 3.3.13. Safety evaluation (including calculation of the MoS) CALCULATION OF THE MARGIN OF SAFETY (4-nitro-o-phenylenediamine) (oxidative) Maximum absorption through the skin A (µg/cm2) = 3.6 µg/cm2 Skin Area surface SAS (cm2) = 700 cm2 Dermal absorption per treatment SAS x A x 0.001 = 2.52 mg Typical body weight of human = 60 kg Systemic exposure dose (SED) SAS x A x 0.001/60 = 0.042 mg/kg No observed adverse effect level NOAEL = 15 mg/kg (rat, oral, 90 day) Margin of Safety NOAEL / SED = 357 3.3.14. Discussion Physico-chemical specifications 4-nitro-o-phenylenediamine is used in oxidative hair dye formulations at a maximum concentration of 0.5%, after mixing with hydrogen peroxide. Stability of 4-nitro-o- phenylenediamine in marketed products is not reported. General toxicity The acute median lethal oral dose of 4-nitro-o-phenylenediamine reported in mice and rats varies from 680 to 2100 mg/kg bw. The majority of the toxico","page":55,"pdf":"sccp_o_093.pdf","row_type":"noael_study","study_id":"sccp_o_093_noael_008"} |
| SCCS Opinion | NOAEL | =0.042 | mg/kg | rat | oral | 90 day | dermal absorption | {"dose":"Safety evaluation (including calculation of the MoS) CALCULATION OF THE MARGIN OF SAFETY (4-nitro-o-phenylenediamine) (oxidative) Maximum absorption through the skin A (µg/cm2) = 3.6 µg/cm2 Skin Area surface SAS (cm2) = 700 cm2 Dermal absorption per treatment SAS x A x 0.001 = 2.52 mg Typical body weight of human = 60 kg Systemic exposure dose (...","effect":"SCCP/0980/06 OPINION ON 4-NITRO-O-PHENYLENEDIAMINE 55 3.3.13. Safety evaluation (including calculation of the MoS) CALCULATION OF THE MARGIN OF SAFETY (4-nitro-o-phenylenediamine) (oxidative) Maximum absorption through the skin A (µg/cm2) = 3.6 µg/cm2 Skin Area surface SAS (cm2) = 700 cm2 Dermal absorption per treatment SAS x A x 0.001 = 2.52 mg Typical body weight of human = 60 kg Systemic exposure dose (SED) SAS x A x 0.001/60 = 0.042 mg/kg No observed adverse effect level NOAEL = 15 mg/kg (rat, oral, 90 day) Margin of Safety NOAEL / SED = 357 3.3.14. Discussion Physico-chemical specifications 4-nitro-o-phenylenediamine is used in oxidative hair dye formulations at a maximum concentration of 0.5%, after mixing with hydrogen peroxide. Stability of 4-nitro-o- phenylenediamine in marketed products is not reported. General toxicity The acute median lethal oral dose of 4-nitro-o-phenylenediamine reported in mice and rats varies from 680 to 2100 mg/kg bw. The majority of the toxico","page":55,"pdf":"sccp_o_093.pdf","row_type":"noael_study","study_id":"sccp_o_093_noael_008"} |
| SCCS Opinion | NOAEL | =0.042 | mg/kg | rat | oral | 90 day | dermal absorption | {"dose":"Safety evaluation (including calculation of the MoS) CALCULATION OF THE MARGIN OF SAFETY (4-nitro-o-phenylenediamine) (oxidative) Maximum absorption through the skin A (µg/cm2) = 3.6 µg/cm2 Skin Area surface SAS (cm2) = 700 cm2 Dermal absorption per treatment SAS x A x 0.001 = 2.52 mg Typical body weight of human = 60 kg Systemic exposure dose (...","effect":"SCCP/0980/06 OPINION ON 4-NITRO-O-PHENYLENEDIAMINE 55 3.3.13. Safety evaluation (including calculation of the MoS) CALCULATION OF THE MARGIN OF SAFETY (4-nitro-o-phenylenediamine) (oxidative) Maximum absorption through the skin A (µg/cm2) = 3.6 µg/cm2 Skin Area surface SAS (cm2) = 700 cm2 Dermal absorption per treatment SAS x A x 0.001 = 2.52 mg Typical body weight of human = 60 kg Systemic exposure dose (SED) SAS x A x 0.001/60 = 0.042 mg/kg No observed adverse effect level NOAEL = 15 mg/kg (rat, oral, 90 day) Margin of Safety NOAEL / SED = 357 3.3.14. Discussion Physico-chemical specifications 4-nitro-o-phenylenediamine is used in oxidative hair dye formulations at a maximum concentration of 0.5%, after mixing with hydrogen peroxide. Stability of 4-nitro-o- phenylenediamine in marketed products is not reported. General toxicity The acute median lethal oral dose of 4-nitro-o-phenylenediamine reported in mice and rats varies from 680 to 2100 mg/kg bw. The majority of the toxico","page":55,"pdf":"sccp_o_093.pdf","row_type":"noael_study","study_id":"sccp_o_093_noael_008"} |
| SCCS Opinion | NOAEL | =15 | mg/kg bw/day | dog | oral | 4-week | NOAEL study | {"dose":"of the highest dose group (still observed after the recovery period) were non-adverse, because a clear trend for reversibility was established.","effect":"of the highest dose group (still observed after the recovery period) were non-adverse, because a clear trend for reversibility was established. However, after a 4-week recovery period minimal hepatocellular hypertrophy was still observed in males of all dose levels. Based on the partly reversible microscopic changes (centrilobular hepatocellular hypertrophy) and reversible increases in (absolute and relative) liver weights, albumin, globulins and proteins in males of the highest dose group, the SCCP considers the NOAEL to be 15 mg/kg bw/day. 3.3.5.3. Chronic (> 12 months) toxicity Guideline: / Species/strain: Beagle dogs Group size: 6 per sex and dose group Test substance: A composite of hair dye formulation containing 0.16% 4-nitro-o- phenylenediamine (and 13 other dyes) Batch: Not specified Purity: Not specified Dose levels: 0, 19.5 and 97.5 mg/kg bw/day hair dye formulation Route: Oral, dietary Vehicle: None Dosing schedule: 7 days/week, 2 years GLP: Not in compliance A 2-year dietary feeding study was conducted in beagle","page":16,"pdf":"sccp_o_093.pdf","row_type":"noael_study","study_id":"sccp_o_093_noael_007"} |
| SCCS Opinion | NOAEL | =15 | mg/kg | rat | oral | 90 day | dermal absorption | {"dose":"Safety evaluation (including calculation of the MoS) CALCULATION OF THE MARGIN OF SAFETY (4-nitro-o-phenylenediamine) (oxidative) Maximum absorption through the skin A (µg/cm2) = 3.6 µg/cm2 Skin Area surface SAS (cm2) = 700 cm2 Dermal absorption per treatment SAS x A x 0.001 = 2.52 mg Typical body weight of human = 60 kg Systemic exposure dose (...","effect":"SCCP/0980/06 OPINION ON 4-NITRO-O-PHENYLENEDIAMINE 55 3.3.13. Safety evaluation (including calculation of the MoS) CALCULATION OF THE MARGIN OF SAFETY (4-nitro-o-phenylenediamine) (oxidative) Maximum absorption through the skin A (µg/cm2) = 3.6 µg/cm2 Skin Area surface SAS (cm2) = 700 cm2 Dermal absorption per treatment SAS x A x 0.001 = 2.52 mg Typical body weight of human = 60 kg Systemic exposure dose (SED) SAS x A x 0.001/60 = 0.042 mg/kg No observed adverse effect level NOAEL = 15 mg/kg (rat, oral, 90 day) Margin of Safety NOAEL / SED = 357 3.3.14. Discussion Physico-chemical specifications 4-nitro-o-phenylenediamine is used in oxidative hair dye formulations at a maximum concentration of 0.5%, after mixing with hydrogen peroxide. Stability of 4-nitro-o- phenylenediamine in marketed products is not reported. General toxicity The acute median lethal oral dose of 4-nitro-o-phenylenediamine reported in mice and rats varies from 680 to 2100 mg/kg bw. The majority of the toxicology s","page":55,"pdf":"sccp_o_093.pdf","row_type":"noael_study","study_id":"sccp_o_093_noael_009"} |
| SCCS Opinion | NOAEL | =15 | mg/kg bw/day | dog | oral | 4-week | NOAEL study | {"dose":"of the highest dose group (still observed after the recovery period) were non-adverse, because a clear trend for reversibility was established.","effect":"of the highest dose group (still observed after the recovery period) were non-adverse, because a clear trend for reversibility was established. However, after a 4-week recovery period minimal hepatocellular hypertrophy was still observed in males of all dose levels. Based on the partly reversible microscopic changes (centrilobular hepatocellular hypertrophy) and reversible increases in (absolute and relative) liver weights, albumin, globulins and proteins in males of the highest dose group, the SCCP considers the NOAEL to be 15 mg/kg bw/day. 3.3.5.3. Chronic (> 12 months) toxicity Guideline: / Species/strain: Beagle dogs Group size: 6 per sex and dose group Test substance: A composite of hair dye formulation containing 0.16% 4-nitro-o- phenylenediamine (and 13 other dyes) Batch: Not specified Purity: Not specified Dose levels: 0, 19.5 and 97.5 mg/kg bw/day hair dye formulation Route: Oral, dietary Vehicle: None Dosing schedule: 7 days/week, 2 years GLP: Not in compliance A 2-year dietary feeding study was conducted in beagle","page":16,"pdf":"sccp_o_093.pdf","row_type":"noael_study","study_id":"sccp_o_093_noael_007"} |
| SCCS Opinion | NOAEL | =15 | mg/kg | rat | oral | 90 day | dermal absorption | {"dose":"Safety evaluation (including calculation of the MoS) CALCULATION OF THE MARGIN OF SAFETY (4-nitro-o-phenylenediamine) (oxidative) Maximum absorption through the skin A (µg/cm2) = 3.6 µg/cm2 Skin Area surface SAS (cm2) = 700 cm2 Dermal absorption per treatment SAS x A x 0.001 = 2.52 mg Typical body weight of human = 60 kg Systemic exposure dose (...","effect":"SCCP/0980/06 OPINION ON 4-NITRO-O-PHENYLENEDIAMINE 55 3.3.13. Safety evaluation (including calculation of the MoS) CALCULATION OF THE MARGIN OF SAFETY (4-nitro-o-phenylenediamine) (oxidative) Maximum absorption through the skin A (µg/cm2) = 3.6 µg/cm2 Skin Area surface SAS (cm2) = 700 cm2 Dermal absorption per treatment SAS x A x 0.001 = 2.52 mg Typical body weight of human = 60 kg Systemic exposure dose (SED) SAS x A x 0.001/60 = 0.042 mg/kg No observed adverse effect level NOAEL = 15 mg/kg (rat, oral, 90 day) Margin of Safety NOAEL / SED = 357 3.3.14. Discussion Physico-chemical specifications 4-nitro-o-phenylenediamine is used in oxidative hair dye formulations at a maximum concentration of 0.5%, after mixing with hydrogen peroxide. Stability of 4-nitro-o- phenylenediamine in marketed products is not reported. General toxicity The acute median lethal oral dose of 4-nitro-o-phenylenediamine reported in mice and rats varies from 680 to 2100 mg/kg bw. The majority of the toxicology s","page":55,"pdf":"sccp_o_093.pdf","row_type":"noael_study","study_id":"sccp_o_093_noael_009"} |
| SCCS Opinion | NOAEL | =15 | mg/kg bw/day | dog | oral | 4-week | NOAEL study | {"dose":"of the highest dose group (still observed after the recovery period) were non-adverse, because a clear trend for reversibility was established.","effect":"of the highest dose group (still observed after the recovery period) were non-adverse, because a clear trend for reversibility was established. However, after a 4-week recovery period minimal hepatocellular hypertrophy was still observed in males of all dose levels. Based on the partly reversible microscopic changes (centrilobular hepatocellular hypertrophy) and reversible increases in (absolute and relative) liver weights, albumin, globulins and proteins in males of the highest dose group, the SCCP considers the NOAEL to be 15 mg/kg bw/day. 3.3.5.3. Chronic (> 12 months) toxicity Guideline: / Species/strain: Beagle dogs Group size: 6 per sex and dose group Test substance: A composite of hair dye formulation containing 0.16% 4-nitro-o- phenylenediamine (and 13 other dyes) Batch: Not specified Purity: Not specified Dose levels: 0, 19.5 and 97.5 mg/kg bw/day hair dye formulation Route: Oral, dietary Vehicle: None Dosing schedule: 7 days/week, 2 years GLP: Not in compliance A 2-year dietary feeding study was conducted in beagle","page":16,"pdf":"sccp_o_093.pdf","row_type":"noael_study","study_id":"sccp_o_093_noael_007"} |
| SCCS Opinion | NOAEL | =15 | mg/kg | rat | oral | 90 day | dermal absorption | {"dose":"Safety evaluation (including calculation of the MoS) CALCULATION OF THE MARGIN OF SAFETY (4-nitro-o-phenylenediamine) (oxidative) Maximum absorption through the skin A (µg/cm2) = 3.6 µg/cm2 Skin Area surface SAS (cm2) = 700 cm2 Dermal absorption per treatment SAS x A x 0.001 = 2.52 mg Typical body weight of human = 60 kg Systemic exposure dose (...","effect":"SCCP/0980/06 OPINION ON 4-NITRO-O-PHENYLENEDIAMINE 55 3.3.13. Safety evaluation (including calculation of the MoS) CALCULATION OF THE MARGIN OF SAFETY (4-nitro-o-phenylenediamine) (oxidative) Maximum absorption through the skin A (µg/cm2) = 3.6 µg/cm2 Skin Area surface SAS (cm2) = 700 cm2 Dermal absorption per treatment SAS x A x 0.001 = 2.52 mg Typical body weight of human = 60 kg Systemic exposure dose (SED) SAS x A x 0.001/60 = 0.042 mg/kg No observed adverse effect level NOAEL = 15 mg/kg (rat, oral, 90 day) Margin of Safety NOAEL / SED = 357 3.3.14. Discussion Physico-chemical specifications 4-nitro-o-phenylenediamine is used in oxidative hair dye formulations at a maximum concentration of 0.5%, after mixing with hydrogen peroxide. Stability of 4-nitro-o- phenylenediamine in marketed products is not reported. General toxicity The acute median lethal oral dose of 4-nitro-o-phenylenediamine reported in mice and rats varies from 680 to 2100 mg/kg bw. The majority of the toxicology s","page":55,"pdf":"sccp_o_093.pdf","row_type":"noael_study","study_id":"sccp_o_093_noael_009"} |
| SCCS Opinion | NOAEL | =15 | mg/kg bw/day | dog | oral | 4-week | NOAEL study | {"dose":"of the highest dose group (still observed after the recovery period) were non-adverse, because a clear trend for reversibility was established.","effect":"of the highest dose group (still observed after the recovery period) were non-adverse, because a clear trend for reversibility was established. However, after a 4-week recovery period minimal hepatocellular hypertrophy was still observed in males of all dose levels. Based on the partly reversible microscopic changes (centrilobular hepatocellular hypertrophy) and reversible increases in (absolute and relative) liver weights, albumin, globulins and proteins in males of the highest dose group, the SCCP considers the NOAEL to be 15 mg/kg bw/day. 3.3.5.3. Chronic (> 12 months) toxicity Guideline: / Species/strain: Beagle dogs Group size: 6 per sex and dose group Test substance: A composite of hair dye formulation containing 0.16% 4-nitro-o- phenylenediamine (and 13 other dyes) Batch: Not specified Purity: Not specified Dose levels: 0, 19.5 and 97.5 mg/kg bw/day hair dye formulation Route: Oral, dietary Vehicle: None Dosing schedule: 7 days/week, 2 years GLP: Not in compliance A 2-year dietary feeding study was conducted in beagle","page":16,"pdf":"sccp_o_093.pdf","row_type":"noael_study","study_id":"sccp_o_093_noael_007"} |
| SCCS Opinion | NOAEL | =15 | mg/kg | rat | oral | 90 day | dermal absorption | {"dose":"Safety evaluation (including calculation of the MoS) CALCULATION OF THE MARGIN OF SAFETY (4-nitro-o-phenylenediamine) (oxidative) Maximum absorption through the skin A (µg/cm2) = 3.6 µg/cm2 Skin Area surface SAS (cm2) = 700 cm2 Dermal absorption per treatment SAS x A x 0.001 = 2.52 mg Typical body weight of human = 60 kg Systemic exposure dose (...","effect":"SCCP/0980/06 OPINION ON 4-NITRO-O-PHENYLENEDIAMINE 55 3.3.13. Safety evaluation (including calculation of the MoS) CALCULATION OF THE MARGIN OF SAFETY (4-nitro-o-phenylenediamine) (oxidative) Maximum absorption through the skin A (µg/cm2) = 3.6 µg/cm2 Skin Area surface SAS (cm2) = 700 cm2 Dermal absorption per treatment SAS x A x 0.001 = 2.52 mg Typical body weight of human = 60 kg Systemic exposure dose (SED) SAS x A x 0.001/60 = 0.042 mg/kg No observed adverse effect level NOAEL = 15 mg/kg (rat, oral, 90 day) Margin of Safety NOAEL / SED = 357 3.3.14. Discussion Physico-chemical specifications 4-nitro-o-phenylenediamine is used in oxidative hair dye formulations at a maximum concentration of 0.5%, after mixing with hydrogen peroxide. Stability of 4-nitro-o- phenylenediamine in marketed products is not reported. General toxicity The acute median lethal oral dose of 4-nitro-o-phenylenediamine reported in mice and rats varies from 680 to 2100 mg/kg bw. The majority of the toxicology s","page":55,"pdf":"sccp_o_093.pdf","row_type":"noael_study","study_id":"sccp_o_093_noael_009"} |
| SCCS Opinion | NOAEL | =45 | mg/kg/day | rat | - | - | NOAEL study | {"dose":"lar hypertrophy persisted after recovery in treated males of all dose levels, whereas females reverted completely.","effect":"lar hypertrophy persisted after recovery in treated males of all dose levels, whereas females reverted completely. After recovery, changes in the thyroid glands of treated male rats were reversible when compared with control males. Marginal evidence of post-treatment changes in the bone marrow of males from the highest dose group (proportion of fatty to hematopoietic marrow was reduced in comparison to the control animals) was reversible after the recovery period. Conclusion Based on the results of this study, a NOEL could not be obtained for 4-nitro-o- phenylenediamine. However, the authors considered all findings to be adaptive or secondary responses to the treatment with the test item and, with the exception of minimal centrilobular hepatocellular hypertrophy of the liver in males previously treated with 45 mg/kg/day, reversible after the recovery period. The centrilobular hepacellular hypertrophy of the liver in males of the highest dose group (still observed after the recovery period) was considered non-adverse, because a","page":16,"pdf":"sccp_o_093.pdf","row_type":"noael_study","study_id":"sccp_o_093_noael_003"} |
| SCCS Opinion | NOAEL | =45 | mg/kg bw/day | - | - | 4-week | NOAEL study | {"citation":"Ref.: 48 Comment The authors considered the NOAEL to be equal to the highest dose level (45 mg/kg bw/day)","dose":"However, the authors considered all findings to be adaptive or secondary responses to the treatment with the test item and, with the exception of minimal centrilobular hepatocellular hypertrophy of the liver in males previously treated with 45 mg/kg/day, reversible after the recovery period.","effect":"ne. However, the authors considered all findings to be adaptive or secondary responses to the treatment with the test item and, with the exception of minimal centrilobular hepatocellular hypertrophy of the liver in males previously treated with 45 mg/kg/day, reversible after the recovery period. The centrilobular hepacellular hypertrophy of the liver in males of the highest dose group (still observed after the recovery period) was considered non-adverse, because a clear trend for reversibility was established. The No Observed Adverse Effect Level (NOAEL) for 4-NOPD was considered to be 45mg/kg bw/day. Ref.: 48 Comment The authors considered the NOAEL to be equal to the highest dose level (45 mg/kg bw/day). They argued that the centrilobular hepacellular hypertrophy of the liver in males of the highest dose group (still observed after the recovery period) were non-adverse, because a clear trend for reversibility was established. However, after a 4-week recovery period minimal hepatocellular hypertrophy was still observed in males of all dose levels. Based","page":16,"pdf":"sccp_o_093.pdf","row_type":"noael_study","study_id":"sccp_o_093_noael_004"} |
| SCCS Opinion | NOAEL | =45 | mg/kg/day | rat | - | - | NOAEL study | {"dose":"lar hypertrophy persisted after recovery in treated males of all dose levels, whereas females reverted completely.","effect":"lar hypertrophy persisted after recovery in treated males of all dose levels, whereas females reverted completely. After recovery, changes in the thyroid glands of treated male rats were reversible when compared with control males. Marginal evidence of post-treatment changes in the bone marrow of males from the highest dose group (proportion of fatty to hematopoietic marrow was reduced in comparison to the control animals) was reversible after the recovery period. Conclusion Based on the results of this study, a NOEL could not be obtained for 4-nitro-o- phenylenediamine. However, the authors considered all findings to be adaptive or secondary responses to the treatment with the test item and, with the exception of minimal centrilobular hepatocellular hypertrophy of the liver in males previously treated with 45 mg/kg/day, reversible after the recovery period. The centrilobular hepacellular hypertrophy of the liver in males of the highest dose group (still observed after the recovery period) was considered non-adverse, because a","page":16,"pdf":"sccp_o_093.pdf","row_type":"noael_study","study_id":"sccp_o_093_noael_003"} |
| SCCS Opinion | NOAEL | =45 | mg/kg bw/day | - | - | 4-week | NOAEL study | {"citation":"Ref.: 48 Comment The authors considered the NOAEL to be equal to the highest dose level (45 mg/kg bw/day)","dose":"However, the authors considered all findings to be adaptive or secondary responses to the treatment with the test item and, with the exception of minimal centrilobular hepatocellular hypertrophy of the liver in males previously treated with 45 mg/kg/day, reversible after the recovery period.","effect":"ne. However, the authors considered all findings to be adaptive or secondary responses to the treatment with the test item and, with the exception of minimal centrilobular hepatocellular hypertrophy of the liver in males previously treated with 45 mg/kg/day, reversible after the recovery period. The centrilobular hepacellular hypertrophy of the liver in males of the highest dose group (still observed after the recovery period) was considered non-adverse, because a clear trend for reversibility was established. The No Observed Adverse Effect Level (NOAEL) for 4-NOPD was considered to be 45mg/kg bw/day. Ref.: 48 Comment The authors considered the NOAEL to be equal to the highest dose level (45 mg/kg bw/day). They argued that the centrilobular hepacellular hypertrophy of the liver in males of the highest dose group (still observed after the recovery period) were non-adverse, because a clear trend for reversibility was established. However, after a 4-week recovery period minimal hepatocellular hypertrophy was still observed in males of all dose levels. Based","page":16,"pdf":"sccp_o_093.pdf","row_type":"noael_study","study_id":"sccp_o_093_noael_004"} |
| SCCS Opinion | NOAEL | =45 | mg/kg/day | rat | - | - | NOAEL study | {"dose":"lar hypertrophy persisted after recovery in treated males of all dose levels, whereas females reverted completely.","effect":"lar hypertrophy persisted after recovery in treated males of all dose levels, whereas females reverted completely. After recovery, changes in the thyroid glands of treated male rats were reversible when compared with control males. Marginal evidence of post-treatment changes in the bone marrow of males from the highest dose group (proportion of fatty to hematopoietic marrow was reduced in comparison to the control animals) was reversible after the recovery period. Conclusion Based on the results of this study, a NOEL could not be obtained for 4-nitro-o- phenylenediamine. However, the authors considered all findings to be adaptive or secondary responses to the treatment with the test item and, with the exception of minimal centrilobular hepatocellular hypertrophy of the liver in males previously treated with 45 mg/kg/day, reversible after the recovery period. The centrilobular hepacellular hypertrophy of the liver in males of the highest dose group (still observed after the recovery period) was considered non-adverse, because a","page":16,"pdf":"sccp_o_093.pdf","row_type":"noael_study","study_id":"sccp_o_093_noael_003"} |
| SCCS Opinion | NOAEL | =45 | mg/kg bw/day | - | - | 4-week | NOAEL study | {"citation":"Ref.: 48 Comment The authors considered the NOAEL to be equal to the highest dose level (45 mg/kg bw/day)","dose":"However, the authors considered all findings to be adaptive or secondary responses to the treatment with the test item and, with the exception of minimal centrilobular hepatocellular hypertrophy of the liver in males previously treated with 45 mg/kg/day, reversible after the recovery period.","effect":"ne. However, the authors considered all findings to be adaptive or secondary responses to the treatment with the test item and, with the exception of minimal centrilobular hepatocellular hypertrophy of the liver in males previously treated with 45 mg/kg/day, reversible after the recovery period. The centrilobular hepacellular hypertrophy of the liver in males of the highest dose group (still observed after the recovery period) was considered non-adverse, because a clear trend for reversibility was established. The No Observed Adverse Effect Level (NOAEL) for 4-NOPD was considered to be 45mg/kg bw/day. Ref.: 48 Comment The authors considered the NOAEL to be equal to the highest dose level (45 mg/kg bw/day). They argued that the centrilobular hepacellular hypertrophy of the liver in males of the highest dose group (still observed after the recovery period) were non-adverse, because a clear trend for reversibility was established. However, after a 4-week recovery period minimal hepatocellular hypertrophy was still observed in males of all dose levels. Based","page":16,"pdf":"sccp_o_093.pdf","row_type":"noael_study","study_id":"sccp_o_093_noael_004"} |
| SCCS Opinion | NOAEL | =45 | mg/kg/day | rat | - | - | NOAEL study | {"dose":"lar hypertrophy persisted after recovery in treated males of all dose levels, whereas females reverted completely.","effect":"lar hypertrophy persisted after recovery in treated males of all dose levels, whereas females reverted completely. After recovery, changes in the thyroid glands of treated male rats were reversible when compared with control males. Marginal evidence of post-treatment changes in the bone marrow of males from the highest dose group (proportion of fatty to hematopoietic marrow was reduced in comparison to the control animals) was reversible after the recovery period. Conclusion Based on the results of this study, a NOEL could not be obtained for 4-nitro-o- phenylenediamine. However, the authors considered all findings to be adaptive or secondary responses to the treatment with the test item and, with the exception of minimal centrilobular hepatocellular hypertrophy of the liver in males previously treated with 45 mg/kg/day, reversible after the recovery period. The centrilobular hepacellular hypertrophy of the liver in males of the highest dose group (still observed after the recovery period) was considered non-adverse, because a","page":16,"pdf":"sccp_o_093.pdf","row_type":"noael_study","study_id":"sccp_o_093_noael_003"} |
| SCCS Opinion | NOAEL | =45 | mg/kg bw/day | - | - | 4-week | NOAEL study | {"citation":"Ref.: 48 Comment The authors considered the NOAEL to be equal to the highest dose level (45 mg/kg bw/day)","dose":"However, the authors considered all findings to be adaptive or secondary responses to the treatment with the test item and, with the exception of minimal centrilobular hepatocellular hypertrophy of the liver in males previously treated with 45 mg/kg/day, reversible after the recovery period.","effect":"ne. However, the authors considered all findings to be adaptive or secondary responses to the treatment with the test item and, with the exception of minimal centrilobular hepatocellular hypertrophy of the liver in males previously treated with 45 mg/kg/day, reversible after the recovery period. The centrilobular hepacellular hypertrophy of the liver in males of the highest dose group (still observed after the recovery period) was considered non-adverse, because a clear trend for reversibility was established. The No Observed Adverse Effect Level (NOAEL) for 4-NOPD was considered to be 45mg/kg bw/day. Ref.: 48 Comment The authors considered the NOAEL to be equal to the highest dose level (45 mg/kg bw/day). They argued that the centrilobular hepacellular hypertrophy of the liver in males of the highest dose group (still observed after the recovery period) were non-adverse, because a clear trend for reversibility was established. However, after a 4-week recovery period minimal hepatocellular hypertrophy was still observed in males of all dose levels. Based","page":16,"pdf":"sccp_o_093.pdf","row_type":"noael_study","study_id":"sccp_o_093_noael_004"} |
| SCCS Opinion | NOAEL | =65 | % | - | oral | 90 day | reproductive toxicity | {"dose":"Since no other measurements of maternal toxicity were conducted, no definite conclusion with respect to the maternal toxic dose could be drawn.","effect":"egnant dams. Since no other measurements of maternal toxicity were conducted, no definite conclusion with respect to the maternal toxic dose could be drawn. Therefore, it can not be ruled out that teratogenic (increased incidence of cleft palate) and embryotoxic (reduced foetal weight) effects occurred at dose levels which were not toxic to the pregnant dams. There are no indications from the old studies and the new 90 day study that e.g. new developmental and/or reproductive studies will identify a (much) low(er) NOAEL. Therefore, and for ethical reasons the SCCP does not ask for new animal studies. Photo-toxicity 4-Nitro-o-phenylenediamine is considered to have no photo-toxic potential. Toxico-kinetics Following oral administration of 4-nitro-o-phenylenediamine, urine was the major route of excretion. At least 65% of the administered 4-nitro-o-phenylenediamine dose was absorbed","page":55,"pdf":"sccp_o_093.pdf","row_type":"noael_study","study_id":"sccp_o_093_noael_013"} |
| SCCS Opinion | NOAEL | =65 | % | - | oral | 90 day | reproductive toxicity | {"dose":"Since no other measurements of maternal toxicity were conducted, no definite conclusion with respect to the maternal toxic dose could be drawn.","effect":"egnant dams. Since no other measurements of maternal toxicity were conducted, no definite conclusion with respect to the maternal toxic dose could be drawn. Therefore, it can not be ruled out that teratogenic (increased incidence of cleft palate) and embryotoxic (reduced foetal weight) effects occurred at dose levels which were not toxic to the pregnant dams. There are no indications from the old studies and the new 90 day study that e.g. new developmental and/or reproductive studies will identify a (much) low(er) NOAEL. Therefore, and for ethical reasons the SCCP does not ask for new animal studies. Photo-toxicity 4-Nitro-o-phenylenediamine is considered to have no photo-toxic potential. Toxico-kinetics Following oral administration of 4-nitro-o-phenylenediamine, urine was the major route of excretion. At least 65% of the administered 4-nitro-o-phenylenediamine dose was absorbed","page":55,"pdf":"sccp_o_093.pdf","row_type":"noael_study","study_id":"sccp_o_093_noael_013"} |
| SCCS Opinion | NOAEL | =65 | % | - | oral | 90 day | reproductive toxicity | {"dose":"Since no other measurements of maternal toxicity were conducted, no definite conclusion with respect to the maternal toxic dose could be drawn.","effect":"egnant dams. Since no other measurements of maternal toxicity were conducted, no definite conclusion with respect to the maternal toxic dose could be drawn. Therefore, it can not be ruled out that teratogenic (increased incidence of cleft palate) and embryotoxic (reduced foetal weight) effects occurred at dose levels which were not toxic to the pregnant dams. There are no indications from the old studies and the new 90 day study that e.g. new developmental and/or reproductive studies will identify a (much) low(er) NOAEL. Therefore, and for ethical reasons the SCCP does not ask for new animal studies. Photo-toxicity 4-Nitro-o-phenylenediamine is considered to have no photo-toxic potential. Toxico-kinetics Following oral administration of 4-nitro-o-phenylenediamine, urine was the major route of excretion. At least 65% of the administered 4-nitro-o-phenylenediamine dose was absorbed","page":55,"pdf":"sccp_o_093.pdf","row_type":"noael_study","study_id":"sccp_o_093_noael_013"} |
| SCCS Opinion | NOAEL | =65 | % | - | oral | 90 day | reproductive toxicity | {"dose":"Since no other measurements of maternal toxicity were conducted, no definite conclusion with respect to the maternal toxic dose could be drawn.","effect":"egnant dams. Since no other measurements of maternal toxicity were conducted, no definite conclusion with respect to the maternal toxic dose could be drawn. Therefore, it can not be ruled out that teratogenic (increased incidence of cleft palate) and embryotoxic (reduced foetal weight) effects occurred at dose levels which were not toxic to the pregnant dams. There are no indications from the old studies and the new 90 day study that e.g. new developmental and/or reproductive studies will identify a (much) low(er) NOAEL. Therefore, and for ethical reasons the SCCP does not ask for new animal studies. Photo-toxicity 4-Nitro-o-phenylenediamine is considered to have no photo-toxic potential. Toxico-kinetics Following oral administration of 4-nitro-o-phenylenediamine, urine was the major route of excretion. At least 65% of the administered 4-nitro-o-phenylenediamine dose was absorbed","page":55,"pdf":"sccp_o_093.pdf","row_type":"noael_study","study_id":"sccp_o_093_noael_013"} |
| SCCS Opinion | NOAEL | =265 | mg/kg/day | - | - | 90 day | developmental toxicity | {"dose":"However, in a new 90 day study the NOAEL is relatively low (15 mg/kg bw/day).","effect":"to 2100 mg/kg bw. The majority of the toxicology studies is old and not performed under current guidelines and GLP. However, in a new 90 day study the NOAEL is relatively low (15 mg/kg bw/day). The studies submitted on reproduction toxicity were publications in open literature and were only of limited use for evaluation. In a teratogenicity study (also publication in open literature) effects on maternal weight gain observed at the lowest observed effect level for teratogenic and embryotoxic effects (265mg/kg/day; NOAEL 128 mg/kg/day) were judged to be equivocal by the applicant. The authors of the publication, however, argued that the effects could be accounted for by the reduction in average foetal weight and concluded that this dose was not toxic to pregnant dams. Since no other measurements of maternal toxicity were conducted, no definite conclusion with respect to the maternal toxic dose could be drawn. Therefore, it can not be ruled out that teratogenic (increased incidence of cleft palate) and embryotoxic (reduced foetal w","page":55,"pdf":"sccp_o_093.pdf","row_type":"noael_study","study_id":"sccp_o_093_noael_012"} |
| SCCS Opinion | NOAEL | =265 | mg/kg/day | - | - | 90 day | developmental toxicity | {"dose":"However, in a new 90 day study the NOAEL is relatively low (15 mg/kg bw/day).","effect":"to 2100 mg/kg bw. The majority of the toxicology studies is old and not performed under current guidelines and GLP. However, in a new 90 day study the NOAEL is relatively low (15 mg/kg bw/day). The studies submitted on reproduction toxicity were publications in open literature and were only of limited use for evaluation. In a teratogenicity study (also publication in open literature) effects on maternal weight gain observed at the lowest observed effect level for teratogenic and embryotoxic effects (265mg/kg/day; NOAEL 128 mg/kg/day) were judged to be equivocal by the applicant. The authors of the publication, however, argued that the effects could be accounted for by the reduction in average foetal weight and concluded that this dose was not toxic to pregnant dams. Since no other measurements of maternal toxicity were conducted, no definite conclusion with respect to the maternal toxic dose could be drawn. Therefore, it can not be ruled out that teratogenic (increased incidence of cleft palate) and embryotoxic (reduced foetal w","page":55,"pdf":"sccp_o_093.pdf","row_type":"noael_study","study_id":"sccp_o_093_noael_012"} |
| SCCS Opinion | NOAEL | =265 | mg/kg/day | - | - | 90 day | developmental toxicity | {"dose":"However, in a new 90 day study the NOAEL is relatively low (15 mg/kg bw/day).","effect":"to 2100 mg/kg bw. The majority of the toxicology studies is old and not performed under current guidelines and GLP. However, in a new 90 day study the NOAEL is relatively low (15 mg/kg bw/day). The studies submitted on reproduction toxicity were publications in open literature and were only of limited use for evaluation. In a teratogenicity study (also publication in open literature) effects on maternal weight gain observed at the lowest observed effect level for teratogenic and embryotoxic effects (265mg/kg/day; NOAEL 128 mg/kg/day) were judged to be equivocal by the applicant. The authors of the publication, however, argued that the effects could be accounted for by the reduction in average foetal weight and concluded that this dose was not toxic to pregnant dams. Since no other measurements of maternal toxicity were conducted, no definite conclusion with respect to the maternal toxic dose could be drawn. Therefore, it can not be ruled out that teratogenic (increased incidence of cleft palate) and embryotoxic (reduced foetal w","page":55,"pdf":"sccp_o_093.pdf","row_type":"noael_study","study_id":"sccp_o_093_noael_012"} |
| SCCS Opinion | NOAEL | =265 | mg/kg/day | - | - | 90 day | developmental toxicity | {"dose":"However, in a new 90 day study the NOAEL is relatively low (15 mg/kg bw/day).","effect":"to 2100 mg/kg bw. The majority of the toxicology studies is old and not performed under current guidelines and GLP. However, in a new 90 day study the NOAEL is relatively low (15 mg/kg bw/day). The studies submitted on reproduction toxicity were publications in open literature and were only of limited use for evaluation. In a teratogenicity study (also publication in open literature) effects on maternal weight gain observed at the lowest observed effect level for teratogenic and embryotoxic effects (265mg/kg/day; NOAEL 128 mg/kg/day) were judged to be equivocal by the applicant. The authors of the publication, however, argued that the effects could be accounted for by the reduction in average foetal weight and concluded that this dose was not toxic to pregnant dams. Since no other measurements of maternal toxicity were conducted, no definite conclusion with respect to the maternal toxic dose could be drawn. Therefore, it can not be ruled out that teratogenic (increased incidence of cleft palate) and embryotoxic (reduced foetal w","page":55,"pdf":"sccp_o_093.pdf","row_type":"noael_study","study_id":"sccp_o_093_noael_012"} |
| SCCS Opinion | NOAEL | =500 | mg/kg | rat | oral | - | NOAEL study | {"dose":"However, it was negative in several independent studies for the induction of micronuclea (mice and rats) and dominant lethals (rats) in vivo, for UDS in HeLa cells and rat hepatocytes in vitro and for SCE in bone marrow and intestinal epithelium of Chinese hamster in vivo (treated up to 500 mg/kg orally).","effect":"-NITRO-O-PHENYLENEDIAMINE 6 induction of chromosome aberrations in mammalian cells grown in vitro. However, it was negative in several independent studies for the induction of micronuclea (mice and rats) and dominant lethals (rats) in vivo, for UDS in HeLa cells and rat hepatocytes in vitro and for SCE in bone marrow and intestinal epithelium of Chinese hamster in vivo (treated up to 500 mg/kg orally). The SCC in its plenary meeting of October 13, 1987 requested a short-term oral toxicity study to determine the NOAEL. A request for a short-term oral toxicity study to determine the NOAEL remains unavailable” Submission VI for this substance was submitted by COLIPA in July 2005. According to this submission the substance is used in oxidative hair dyes to a maximum concentration of 1.0%. After mixing 1:1 with hydrogen peroxide, the concentration on the scalp is 0.5%. Submission VI presents updated scientific data on the above mentioned substance in line with the second step of the strategy for the evaluation of hair dyes (http:","page":6,"pdf":"sccp_o_093.pdf","row_type":"noael_study","study_id":"sccp_o_093_noael_001"} |
| SCCS Opinion | NOAEL | =500 | mg/kg | rat | oral | - | NOAEL study | {"dose":"However, it was negative in several independent studies for the induction of micronuclea (mice and rats) and dominant lethals (rats) in vivo, for UDS in HeLa cells and rat hepatocytes in vitro and for SCE in bone marrow and intestinal epithelium of Chinese hamster in vivo (treated up to 500 mg/kg orally).","effect":"-NITRO-O-PHENYLENEDIAMINE 6 induction of chromosome aberrations in mammalian cells grown in vitro. However, it was negative in several independent studies for the induction of micronuclea (mice and rats) and dominant lethals (rats) in vivo, for UDS in HeLa cells and rat hepatocytes in vitro and for SCE in bone marrow and intestinal epithelium of Chinese hamster in vivo (treated up to 500 mg/kg orally). The SCC in its plenary meeting of October 13, 1987 requested a short-term oral toxicity study to determine the NOAEL. A request for a short-term oral toxicity study to determine the NOAEL remains unavailable” Submission VI for this substance was submitted by COLIPA in July 2005. According to this submission the substance is used in oxidative hair dyes to a maximum concentration of 1.0%. After mixing 1:1 with hydrogen peroxide, the concentration on the scalp is 0.5%. Submission VI presents updated scientific data on the above mentioned substance in line with the second step of the strategy for the evaluation of hair dyes (http:","page":6,"pdf":"sccp_o_093.pdf","row_type":"noael_study","study_id":"sccp_o_093_noael_001"} |
| SCCS Opinion | NOAEL | =500 | mg/kg | rat | oral | - | NOAEL study | {"dose":"However, it was negative in several independent studies for the induction of micronuclea (mice and rats) and dominant lethals (rats) in vivo, for UDS in HeLa cells and rat hepatocytes in vitro and for SCE in bone marrow and intestinal epithelium of Chinese hamster in vivo (treated up to 500 mg/kg orally).","effect":"-NITRO-O-PHENYLENEDIAMINE 6 induction of chromosome aberrations in mammalian cells grown in vitro. However, it was negative in several independent studies for the induction of micronuclea (mice and rats) and dominant lethals (rats) in vivo, for UDS in HeLa cells and rat hepatocytes in vitro and for SCE in bone marrow and intestinal epithelium of Chinese hamster in vivo (treated up to 500 mg/kg orally). The SCC in its plenary meeting of October 13, 1987 requested a short-term oral toxicity study to determine the NOAEL. A request for a short-term oral toxicity study to determine the NOAEL remains unavailable” Submission VI for this substance was submitted by COLIPA in July 2005. According to this submission the substance is used in oxidative hair dyes to a maximum concentration of 1.0%. After mixing 1:1 with hydrogen peroxide, the concentration on the scalp is 0.5%. Submission VI presents updated scientific data on the above mentioned substance in line with the second step of the strategy for the evaluation of hair dyes (http:","page":6,"pdf":"sccp_o_093.pdf","row_type":"noael_study","study_id":"sccp_o_093_noael_001"} |
| SCCS Opinion | NOAEL | =500 | mg/kg | rat | oral | - | NOAEL study | {"dose":"However, it was negative in several independent studies for the induction of micronuclea (mice and rats) and dominant lethals (rats) in vivo, for UDS in HeLa cells and rat hepatocytes in vitro and for SCE in bone marrow and intestinal epithelium of Chinese hamster in vivo (treated up to 500 mg/kg orally).","effect":"-NITRO-O-PHENYLENEDIAMINE 6 induction of chromosome aberrations in mammalian cells grown in vitro. However, it was negative in several independent studies for the induction of micronuclea (mice and rats) and dominant lethals (rats) in vivo, for UDS in HeLa cells and rat hepatocytes in vitro and for SCE in bone marrow and intestinal epithelium of Chinese hamster in vivo (treated up to 500 mg/kg orally). The SCC in its plenary meeting of October 13, 1987 requested a short-term oral toxicity study to determine the NOAEL. A request for a short-term oral toxicity study to determine the NOAEL remains unavailable” Submission VI for this substance was submitted by COLIPA in July 2005. According to this submission the substance is used in oxidative hair dyes to a maximum concentration of 1.0%. After mixing 1:1 with hydrogen peroxide, the concentration on the scalp is 0.5%. Submission VI presents updated scientific data on the above mentioned substance in line with the second step of the strategy for the evaluation of hair dyes (http:","page":6,"pdf":"sccp_o_093.pdf","row_type":"noael_study","study_id":"sccp_o_093_noael_001"} |
ToxValDB ECOTOX 2 endpoints
| Source | Endpoint Type | Value | Unit | Species | Route | Duration | Study Type | Reference |
|---|---|---|---|---|---|---|---|---|
| ToxValDB ECOTOX | NOEL | =340 | mg/kg bw/day | Rat | oral | short-term; 1.625 days | short-term | LONG_REF=Mutat. Res.320(3): 189-205 Uno,Y., H. Takasawa, M. Miyagawa, Y. Inoue, T. Murata, and K. Yoshikawa An In Vivo-In Vitro Replicative DNA Synthesis (RDS) Test Using Rat Hepatocytes as an Early Prediction Assay for Nongenotoxic Hepatocarcinogens Screening of 22 Known Positive and 25 Noncarcinogens 1994; TITLE=An In Vivo-In Vitro Replicative DNA Synthesis (RDS) Test Using Rat Hepatocytes as an Early Prediction Assay for Nongenotoxic Hepatocarcinogens Screening of 22 Known Positive and 25 Noncarcinogens; AUTHOR=Uno,Y., H. Takasawa, M. Miyagawa, Y. Inoue, T. Murata, and K. Yoshikawa; DOI=10.1016/0165-1218(94)90046-9; QUALITY=Control type: Concurrent control; EXTERNAL_SOURCE_ID=75058; EXTERNAL_SOURCE_ID_DESC=ECOTOX Reference Number; STORED_SOURCE_RECORD=https://clowder.edap-cluster.com/files/6759bce8e4b0a7c65d37bc5f; RECORD_SOURCE_LEVEL=Extraction document; SOURCE_URL=https://cfpub.epa.gov/ecotox/; YEAR=1994; ORIGINAL_YEAR=1994; TOXICOLOGICAL_EFFECT=Cell(s): Viability; STUDY_GROUP=ECOTOX:15605215:M:--; QC_CATEGORY=Data source QC'd by data provider prior to ECOTOX import; QC_STATUS=not determined; SOURCE_HASH=0ceae7e0d1921ce655d9d34645c00e53 |
| ToxValDB ECOTOX | NOEL | =500 | mg/kg bw/day | Mouse | oral | short-term; 2 days | short-term | LONG_REF=Mutat. Res.343(2/3): 157-183 Miyagawa,M., H. Takasawa, A. Sugiyama, Y. Inoue, T. Murata, Y. Uno, and K. Yoshikawa The In Vivo-In Vitro Replicative DNA Synthesis (RDS) Test with Hepatocytes Prepared from Male B6C3F1 Mice as an Early Prediction Assay for Putative Nongenotoxic (Ames-Negative) Mouse Hepatocarcinogens 1995; TITLE=The In Vivo-In Vitro Replicative DNA Synthesis (RDS) Test with Hepatocytes Prepared from Male B6C3F1 Mice as an Early Prediction Assay for Putative Nongenotoxic (Ames-Negative) Mouse Hepatocarcinogens; AUTHOR=Miyagawa,M., H. Takasawa, A. Sugiyama, Y. Inoue, T. Murata, Y. Uno, and K. Yoshikawa; DOI=10.1016/0165-1218(95)90082-9; QUALITY=Control type: Carrier or solvent control; EXTERNAL_SOURCE_ID=75052; EXTERNAL_SOURCE_ID_DESC=ECOTOX Reference Number; STORED_SOURCE_RECORD=https://clowder.edap-cluster.com/files/6759bce8e4b0a7c65d37bc5f; RECORD_SOURCE_LEVEL=Extraction document; SOURCE_URL=https://cfpub.epa.gov/ecotox/; YEAR=1995; ORIGINAL_YEAR=1995; TOXICOLOGICAL_EFFECT=Cell(s): Viability; STUDY_GROUP=ECOTOX:15603526:M:--; QC_CATEGORY=Data source QC'd by data provider prior to ECOTOX import; QC_STATUS=not determined; SOURCE_HASH=4dfae0571c47d2f4be1e1bce34b77746 |
Regulatory source 13 endpoints
| Source | Endpoint Type | Value | Unit | Species | Route | Duration | Study Type | Reference |
|---|---|---|---|---|---|---|---|---|
| Regulatory source | - | 15 | mg/kg bw/day | dog | oral | 4-week | - | SOURCE_SUBDIR=sccp_o_093; REPORT_TITLE=OPINION ON 4-NITRO-O-PHENYLENEDIAMINE COLIPA N° B24; OPINION_NUMBER=SCCP/0980/06; COMMITTEE=Scientific Committee on Consumer Products (SCCP); REPORT_DATE=19 December 2006; VALUE_TEXT=15; DOSE=of the highest dose group (still observed after the recovery period) were non-adverse, because a clear trend for reversibility was established.; EFFECT=of the highest dose group (still observed after the recovery period) were non-adverse, because a clear trend for reversibility was established. However, after a 4-week recovery period minimal hepatocellular hypertrophy was still observed in males of all dose levels. Based on the partly reversible microscopic changes (centrilobular hepatocellular hypertrophy) and reversible increases in (absolute and relative) liver weights, albumin, globulins and proteins in males of the highest dose group, the SCCP considers the NOAEL to be 15 mg/kg bw/day. 3.3.5.3. Chronic (> 12 months) toxicity Guideline: / Species/strain: Beagle dogs Group size: 6 per sex and dose group Test substance: A composite of hair dye formulation containing 0.16% 4-nitro-o- phenylenediamine (and 13 other dyes) Batch: Not specified Purity: Not specified Dose levels: 0, 19.5 and 97.5 mg/kg bw/day hair dye formulation Route: Oral, dietary Vehicle: None Dosing schedule: 7 days/week, 2 years GLP: Not in compliance A 2-year dietary feeding study was conducted in beagle; CITATION_NUMBERS=[]; DETAILS_JSON={"cas_number":"99-56-9","citation":"","dose":"of the highest dose group (still observed after the recovery period) were non-adverse, because a clear trend for reversibility was established.","duration":"4-week","effect":"of the highest dose group (still observed after the recovery period) were non-adverse, because a clear trend for reversibility was established. However, after a 4-week recovery period minimal hepatocellular hypertrophy was still observed in males of all dose levels. Based on the partly reversible microscopic changes (centrilobular hepatocellular hypertrophy) and reversible increases in (absolute and relative) liver weights, albumin, globulins and proteins in males of the highest dose group, the SCCP considers the NOAEL to be 15 mg/kg bw/day. 3.3.5.3. Chronic (> 12 months) toxicity Guideline: / Species/strain: Beagle dogs Group size: 6 per sex and dose group Test substance: A composite of hair dye formulation containing 0.16% 4-nitro-o- phenylenediamine (and 13 other dyes) Batch: Not specified Purity: Not specified Dose levels: 0, 19.5 and 97.5 mg/kg bw/day hair dye formulation Route: Oral, dietary Vehicle: None Dosing schedule: 7 days/week, 2 years GLP: Not in compliance A 2-year dietary feeding study was conducted in beagle","endpoint":"","ingredient":"was submitted in December 1981 by COLIPA.","loael_value":"","noael_unit":"mg/kg bw/day","noael_value":"15","page":16,"route":"oral","species":"dog","study_id":"sccp_o_093_noael_007"} |
| Regulatory source | - | 45 | mg/kg/day | rat | - | - | - | SOURCE_SUBDIR=sccp_o_093; REPORT_TITLE=OPINION ON 4-NITRO-O-PHENYLENEDIAMINE COLIPA N° B24; OPINION_NUMBER=SCCP/0980/06; COMMITTEE=Scientific Committee on Consumer Products (SCCP); REPORT_DATE=19 December 2006; VALUE_TEXT=45; DOSE=lar hypertrophy persisted after recovery in treated males of all dose levels, whereas females reverted completely.; EFFECT=lar hypertrophy persisted after recovery in treated males of all dose levels, whereas females reverted completely. After recovery, changes in the thyroid glands of treated male rats were reversible when compared with control males. Marginal evidence of post-treatment changes in the bone marrow of males from the highest dose group (proportion of fatty to hematopoietic marrow was reduced in comparison to the control animals) was reversible after the recovery period. Conclusion Based on the results of this study, a NOEL could not be obtained for 4-nitro-o- phenylenediamine. However, the authors considered all findings to be adaptive or secondary responses to the treatment with the test item and, with the exception of minimal centrilobular hepatocellular hypertrophy of the liver in males previously treated with 45 mg/kg/day, reversible after the recovery period. The centrilobular hepacellular hypertrophy of the liver in males of the highest dose group (still observed after the recovery period) was considered non-adverse, because a; CITATION_NUMBERS=[]; DETAILS_JSON={"cas_number":"99-56-9","citation":"","dose":"lar hypertrophy persisted after recovery in treated males of all dose levels, whereas females reverted completely.","duration":"","effect":"lar hypertrophy persisted after recovery in treated males of all dose levels, whereas females reverted completely. After recovery, changes in the thyroid glands of treated male rats were reversible when compared with control males. Marginal evidence of post-treatment changes in the bone marrow of males from the highest dose group (proportion of fatty to hematopoietic marrow was reduced in comparison to the control animals) was reversible after the recovery period. Conclusion Based on the results of this study, a NOEL could not be obtained for 4-nitro-o- phenylenediamine. However, the authors considered all findings to be adaptive or secondary responses to the treatment with the test item and, with the exception of minimal centrilobular hepatocellular hypertrophy of the liver in males previously treated with 45 mg/kg/day, reversible after the recovery period. The centrilobular hepacellular hypertrophy of the liver in males of the highest dose group (still observed after the recovery period) was considered non-adverse, because a","endpoint":"","ingredient":"was submitted in December 1981 by COLIPA.","loael_value":"","noael_unit":"mg/kg/day","noael_value":"45","page":16,"route":"","species":"rat","study_id":"sccp_o_093_noael_003"} |
| Regulatory source | - | 45 | mg/kg bw/day | - | - | 4-week | - | SOURCE_SUBDIR=sccp_o_093; REPORT_TITLE=OPINION ON 4-NITRO-O-PHENYLENEDIAMINE COLIPA N° B24; OPINION_NUMBER=SCCP/0980/06; COMMITTEE=Scientific Committee on Consumer Products (SCCP); REPORT_DATE=19 December 2006; VALUE_TEXT=45; DOSE=However, the authors considered all findings to be adaptive or secondary responses to the treatment with the test item and, with the exception of minimal centrilobular hepatocellular hypertrophy of the liver in males previously treated with 45 mg/kg/day, reversible after the recovery period.; EFFECT=ne. However, the authors considered all findings to be adaptive or secondary responses to the treatment with the test item and, with the exception of minimal centrilobular hepatocellular hypertrophy of the liver in males previously treated with 45 mg/kg/day, reversible after the recovery period. The centrilobular hepacellular hypertrophy of the liver in males of the highest dose group (still observed after the recovery period) was considered non-adverse, because a clear trend for reversibility was established. The No Observed Adverse Effect Level (NOAEL) for 4-NOPD was considered to be 45mg/kg bw/day. Ref.: 48 Comment The authors considered the NOAEL to be equal to the highest dose level (45 mg/kg bw/day). They argued that the centrilobular hepacellular hypertrophy of the liver in males of the highest dose group (still observed after the recovery period) were non-adverse, because a clear trend for reversibility was established. However, after a 4-week recovery period minimal hepatocellular hypertrophy was still observed in males of all dose levels. Based; CITATION=Ref.: 48 Comment The authors considered the NOAEL to be equal to the highest dose level (45 mg/kg bw/day); CITATION_NUMBERS=[48,45]; REFERENCE=Ref.: 48 Comment The authors considered the NOAEL to be equal to the highest dose level (45 mg/kg bw/day); DETAILS_JSON={"cas_number":"99-56-9","citation":"Ref.: 48 Comment The authors considered the NOAEL to be equal to the highest dose level (45 mg/kg bw/day)","dose":"However, the authors considered all findings to be adaptive or secondary responses to the treatment with the test item and, with the exception of minimal centrilobular hepatocellular hypertrophy of the liver in males previously treated with 45 mg/kg/day, reversible after the recovery period.","duration":"4-week","effect":"ne. However, the authors considered all findings to be adaptive or secondary responses to the treatment with the test item and, with the exception of minimal centrilobular hepatocellular hypertrophy of the liver in males previously treated with 45 mg/kg/day, reversible after the recovery period. The centrilobular hepacellular hypertrophy of the liver in males of the highest dose group (still observed after the recovery period) was considered non-adverse, because a clear trend for reversibility was established. The No Observed Adverse Effect Level (NOAEL) for 4-NOPD was considered to be 45mg/kg bw/day. Ref.: 48 Comment The authors considered the NOAEL to be equal to the highest dose level (45 mg/kg bw/day). They argued that the centrilobular hepacellular hypertrophy of the liver in males of the highest dose group (still observed after the recovery period) were non-adverse, because a clear trend for reversibility was established. However, after a 4-week recovery period minimal hepatocellular hypertrophy was still observed in males of all dose levels. Based","endpoint":"","ingredient":"was submitted in December 1981 by COLIPA.","loael_value":"","noael_unit":"mg/kg bw/day","noael_value":"45","page":16,"route":"","species":"","study_id":"sccp_o_093_noael_004"} |
| Regulatory source | - | 45 | mg/kg bw/day | - | - | 4-week | - | SOURCE_SUBDIR=sccp_o_093; REPORT_TITLE=OPINION ON 4-NITRO-O-PHENYLENEDIAMINE COLIPA N° B24; OPINION_NUMBER=SCCP/0980/06; COMMITTEE=Scientific Committee on Consumer Products (SCCP); REPORT_DATE=19 December 2006; VALUE_TEXT=45; DOSE=d all findings to be adaptive or secondary responses to the treatment with the test item and, with the exception of minimal centrilobular hepatocellular hypertrophy of the liver in males previously treated with 45 mg/kg/day, reversible after the recovery period.; EFFECT=d all findings to be adaptive or secondary responses to the treatment with the test item and, with the exception of minimal centrilobular hepatocellular hypertrophy of the liver in males previously treated with 45 mg/kg/day, reversible after the recovery period. The centrilobular hepacellular hypertrophy of the liver in males of the highest dose group (still observed after the recovery period) was considered non-adverse, because a clear trend for reversibility was established. The No Observed Adverse Effect Level (NOAEL) for 4-NOPD was considered to be 45mg/kg bw/day. Ref.: 48 Comment The authors considered the NOAEL to be equal to the highest dose level (45 mg/kg bw/day). They argued that the centrilobular hepacellular hypertrophy of the liver in males of the highest dose group (still observed after the recovery period) were non-adverse, because a clear trend for reversibility was established. However, after a 4-week recovery period minimal hepatocellular hypertrophy was still observed in males of all dose levels. Based on the; CITATION=Ref.: 48 Comment The authors considered the NOAEL to be equal to the highest dose level (45 mg/kg bw/day); CITATION_NUMBERS=[48,45]; REFERENCE=Ref.: 48 Comment The authors considered the NOAEL to be equal to the highest dose level (45 mg/kg bw/day); DETAILS_JSON={"cas_number":"99-56-9","citation":"Ref.: 48 Comment The authors considered the NOAEL to be equal to the highest dose level (45 mg/kg bw/day)","dose":"d all findings to be adaptive or secondary responses to the treatment with the test item and, with the exception of minimal centrilobular hepatocellular hypertrophy of the liver in males previously treated with 45 mg/kg/day, reversible after the recovery period.","duration":"4-week","effect":"d all findings to be adaptive or secondary responses to the treatment with the test item and, with the exception of minimal centrilobular hepatocellular hypertrophy of the liver in males previously treated with 45 mg/kg/day, reversible after the recovery period. The centrilobular hepacellular hypertrophy of the liver in males of the highest dose group (still observed after the recovery period) was considered non-adverse, because a clear trend for reversibility was established. The No Observed Adverse Effect Level (NOAEL) for 4-NOPD was considered to be 45mg/kg bw/day. Ref.: 48 Comment The authors considered the NOAEL to be equal to the highest dose level (45 mg/kg bw/day). They argued that the centrilobular hepacellular hypertrophy of the liver in males of the highest dose group (still observed after the recovery period) were non-adverse, because a clear trend for reversibility was established. However, after a 4-week recovery period minimal hepatocellular hypertrophy was still observed in males of all dose levels. Based on the","endpoint":"","ingredient":"was submitted in December 1981 by COLIPA.","loael_value":"","noael_unit":"mg/kg bw/day","noael_value":"45","page":16,"route":"","species":"","study_id":"sccp_o_093_noael_005"} |
| Regulatory source | - | 45 | mg/kg bw/day | - | - | 4-week | - | SOURCE_SUBDIR=sccp_o_093; REPORT_TITLE=OPINION ON 4-NITRO-O-PHENYLENEDIAMINE COLIPA N° B24; OPINION_NUMBER=SCCP/0980/06; COMMITTEE=Scientific Committee on Consumer Products (SCCP); REPORT_DATE=19 December 2006; VALUE_TEXT=45; DOSE=he exception of minimal centrilobular hepatocellular hypertrophy of the liver in males previously treated with 45 mg/kg/day, reversible after the recovery period.; EFFECT=he exception of minimal centrilobular hepatocellular hypertrophy of the liver in males previously treated with 45 mg/kg/day, reversible after the recovery period. The centrilobular hepacellular hypertrophy of the liver in males of the highest dose group (still observed after the recovery period) was considered non-adverse, because a clear trend for reversibility was established. The No Observed Adverse Effect Level (NOAEL) for 4-NOPD was considered to be 45mg/kg bw/day. Ref.: 48 Comment The authors considered the NOAEL to be equal to the highest dose level (45 mg/kg bw/day). They argued that the centrilobular hepacellular hypertrophy of the liver in males of the highest dose group (still observed after the recovery period) were non-adverse, because a clear trend for reversibility was established. However, after a 4-week recovery period minimal hepatocellular hypertrophy was still observed in males of all dose levels. Based on the partly reversible microscopic changes (centrilobular hepatocellular hypertrophy) and reversible incr; CITATION=Ref.: 48 Comment The authors considered the NOAEL to be equal to the highest dose level (45 mg/kg bw/day); CITATION_NUMBERS=[48,45]; REFERENCE=Ref.: 48 Comment The authors considered the NOAEL to be equal to the highest dose level (45 mg/kg bw/day); DETAILS_JSON={"cas_number":"99-56-9","citation":"Ref.: 48 Comment The authors considered the NOAEL to be equal to the highest dose level (45 mg/kg bw/day)","dose":"he exception of minimal centrilobular hepatocellular hypertrophy of the liver in males previously treated with 45 mg/kg/day, reversible after the recovery period.","duration":"4-week","effect":"he exception of minimal centrilobular hepatocellular hypertrophy of the liver in males previously treated with 45 mg/kg/day, reversible after the recovery period. The centrilobular hepacellular hypertrophy of the liver in males of the highest dose group (still observed after the recovery period) was considered non-adverse, because a clear trend for reversibility was established. The No Observed Adverse Effect Level (NOAEL) for 4-NOPD was considered to be 45mg/kg bw/day. Ref.: 48 Comment The authors considered the NOAEL to be equal to the highest dose level (45 mg/kg bw/day). They argued that the centrilobular hepacellular hypertrophy of the liver in males of the highest dose group (still observed after the recovery period) were non-adverse, because a clear trend for reversibility was established. However, after a 4-week recovery period minimal hepatocellular hypertrophy was still observed in males of all dose levels. Based on the partly reversible microscopic changes (centrilobular hepatocellular hypertrophy) and reversible incr","endpoint":"","ingredient":"was submitted in December 1981 by COLIPA.","loael_value":"","noael_unit":"mg/kg bw/day","noael_value":"45","page":16,"route":"","species":"","study_id":"sccp_o_093_noael_006"} |
| Regulatory source | - | 500 | mg/kg | rat | oral | - | - | SOURCE_SUBDIR=sccp_o_093; REPORT_TITLE=OPINION ON 4-NITRO-O-PHENYLENEDIAMINE COLIPA N° B24; OPINION_NUMBER=SCCP/0980/06; COMMITTEE=Scientific Committee on Consumer Products (SCCP); REPORT_DATE=19 December 2006; VALUE_TEXT=500; DOSE=However, it was negative in several independent studies for the induction of micronuclea (mice and rats) and dominant lethals (rats) in vivo, for UDS in HeLa cells and rat hepatocytes in vitro and for SCE in bone marrow and intestinal epithelium of Chinese hamster in vivo (treated up to 500 mg/kg orally).; EFFECT=-NITRO-O-PHENYLENEDIAMINE 6 induction of chromosome aberrations in mammalian cells grown in vitro. However, it was negative in several independent studies for the induction of micronuclea (mice and rats) and dominant lethals (rats) in vivo, for UDS in HeLa cells and rat hepatocytes in vitro and for SCE in bone marrow and intestinal epithelium of Chinese hamster in vivo (treated up to 500 mg/kg orally). The SCC in its plenary meeting of October 13, 1987 requested a short-term oral toxicity study to determine the NOAEL. A request for a short-term oral toxicity study to determine the NOAEL remains unavailable” Submission VI for this substance was submitted by COLIPA in July 2005. According to this submission the substance is used in oxidative hair dyes to a maximum concentration of 1.0%. After mixing 1:1 with hydrogen peroxide, the concentration on the scalp is 0.5%. Submission VI presents updated scientific data on the above mentioned substance in line with the second step of the strategy for the evaluation of hair dyes (http:; CITATION_NUMBERS=[]; DETAILS_JSON={"cas_number":"99-56-9","citation":"","dose":"However, it was negative in several independent studies for the induction of micronuclea (mice and rats) and dominant lethals (rats) in vivo, for UDS in HeLa cells and rat hepatocytes in vitro and for SCE in bone marrow and intestinal epithelium of Chinese hamster in vivo (treated up to 500 mg/kg orally).","duration":"","effect":"-NITRO-O-PHENYLENEDIAMINE 6 induction of chromosome aberrations in mammalian cells grown in vitro. However, it was negative in several independent studies for the induction of micronuclea (mice and rats) and dominant lethals (rats) in vivo, for UDS in HeLa cells and rat hepatocytes in vitro and for SCE in bone marrow and intestinal epithelium of Chinese hamster in vivo (treated up to 500 mg/kg orally). The SCC in its plenary meeting of October 13, 1987 requested a short-term oral toxicity study to determine the NOAEL. A request for a short-term oral toxicity study to determine the NOAEL remains unavailable” Submission VI for this substance was submitted by COLIPA in July 2005. According to this submission the substance is used in oxidative hair dyes to a maximum concentration of 1.0%. After mixing 1:1 with hydrogen peroxide, the concentration on the scalp is 0.5%. Submission VI presents updated scientific data on the above mentioned substance in line with the second step of the strategy for the evaluation of hair dyes (http:","endpoint":"","ingredient":"was submitted in December 1981 by COLIPA.","loael_value":"","noael_unit":"mg/kg","noael_value":"500","page":6,"route":"oral","species":"rat","study_id":"sccp_o_093_noael_001"} |
| Regulatory source | - | 500 | mg/kg | rat | oral | - | - | SOURCE_SUBDIR=sccp_o_093; REPORT_TITLE=OPINION ON 4-NITRO-O-PHENYLENEDIAMINE COLIPA N° B24; OPINION_NUMBER=SCCP/0980/06; COMMITTEE=Scientific Committee on Consumer Products (SCCP); REPORT_DATE=19 December 2006; VALUE_TEXT=500; DOSE=However, it was negative in several independent studies for the induction of micronuclea (mice and rats) and dominant lethals (rats) in vivo, for UDS in HeLa cells and rat hepatocytes in vitro and for SCE in bone marrow and intestinal epithelium of Chinese hamster in vivo (treated up to 500 mg/kg orally).; EFFECT=malian cells grown in vitro. However, it was negative in several independent studies for the induction of micronuclea (mice and rats) and dominant lethals (rats) in vivo, for UDS in HeLa cells and rat hepatocytes in vitro and for SCE in bone marrow and intestinal epithelium of Chinese hamster in vivo (treated up to 500 mg/kg orally). The SCC in its plenary meeting of October 13, 1987 requested a short-term oral toxicity study to determine the NOAEL. A request for a short-term oral toxicity study to determine the NOAEL remains unavailable” Submission VI for this substance was submitted by COLIPA in July 2005. According to this submission the substance is used in oxidative hair dyes to a maximum concentration of 1.0%. After mixing 1:1 with hydrogen peroxide, the concentration on the scalp is 0.5%. Submission VI presents updated scientific data on the above mentioned substance in line with the second step of the strategy for the evaluation of hair dyes (http://europa.eu.int/comm/enterprise/cosmetics/doc/hairdyestrategyinternet.pd; CITATION_NUMBERS=[]; DETAILS_JSON={"cas_number":"99-56-9","citation":"","dose":"However, it was negative in several independent studies for the induction of micronuclea (mice and rats) and dominant lethals (rats) in vivo, for UDS in HeLa cells and rat hepatocytes in vitro and for SCE in bone marrow and intestinal epithelium of Chinese hamster in vivo (treated up to 500 mg/kg orally).","duration":"","effect":"malian cells grown in vitro. However, it was negative in several independent studies for the induction of micronuclea (mice and rats) and dominant lethals (rats) in vivo, for UDS in HeLa cells and rat hepatocytes in vitro and for SCE in bone marrow and intestinal epithelium of Chinese hamster in vivo (treated up to 500 mg/kg orally). The SCC in its plenary meeting of October 13, 1987 requested a short-term oral toxicity study to determine the NOAEL. A request for a short-term oral toxicity study to determine the NOAEL remains unavailable” Submission VI for this substance was submitted by COLIPA in July 2005. According to this submission the substance is used in oxidative hair dyes to a maximum concentration of 1.0%. After mixing 1:1 with hydrogen peroxide, the concentration on the scalp is 0.5%. Submission VI presents updated scientific data on the above mentioned substance in line with the second step of the strategy for the evaluation of hair dyes (http://europa.eu.int/comm/enterprise/cosmetics/doc/hairdyestrategyinternet.pd","endpoint":"","ingredient":"was submitted in December 1981 by COLIPA.","loael_value":"","noael_unit":"mg/kg","noael_value":"500","page":6,"route":"oral","species":"rat","study_id":"sccp_o_093_noael_002"} |
| Regulatory source | dermal absorption | =0.042 | mg/kg | rat | oral | 90 day | dermal absorption | SOURCE_SUBDIR=sccp_o_093; REPORT_TITLE=OPINION ON 4-NITRO-O-PHENYLENEDIAMINE COLIPA N° B24; OPINION_NUMBER=SCCP/0980/06; COMMITTEE=Scientific Committee on Consumer Products (SCCP); REPORT_DATE=19 December 2006; VALUE_TEXT== 0.042; DOSE=Safety evaluation (including calculation of the MoS) CALCULATION OF THE MARGIN OF SAFETY (4-nitro-o-phenylenediamine) (oxidative) Maximum absorption through the skin A (µg/cm2) = 3.6 µg/cm2 Skin Area surface SAS (cm2) = 700 cm2 Dermal absorption per treatment SAS x A x 0.001 = 2.52 mg Typical body weight of human = 60 kg Systemic exposure dose (...; EFFECT=SCCP/0980/06 OPINION ON 4-NITRO-O-PHENYLENEDIAMINE 55 3.3.13. Safety evaluation (including calculation of the MoS) CALCULATION OF THE MARGIN OF SAFETY (4-nitro-o-phenylenediamine) (oxidative) Maximum absorption through the skin A (µg/cm2) = 3.6 µg/cm2 Skin Area surface SAS (cm2) = 700 cm2 Dermal absorption per treatment SAS x A x 0.001 = 2.52 mg Typical body weight of human = 60 kg Systemic exposure dose (SED) SAS x A x 0.001/60 = 0.042 mg/kg No observed adverse effect level NOAEL = 15 mg/kg (rat, oral, 90 day) Margin of Safety NOAEL / SED = 357 3.3.14. Discussion Physico-chemical specifications 4-nitro-o-phenylenediamine is used in oxidative hair dye formulations at a maximum concentration of 0.5%, after mixing with hydrogen peroxide. Stability of 4-nitro-o- phenylenediamine in marketed products is not reported. General toxicity The acute median lethal oral dose of 4-nitro-o-phenylenediamine reported in mice and rats varies from 680 to 2100 mg/kg bw. The majority of the toxico; CITATION_NUMBERS=[]; DETAILS_JSON={"cas_number":"99-56-9","citation":"","dose":"Safety evaluation (including calculation of the MoS) CALCULATION OF THE MARGIN OF SAFETY (4-nitro-o-phenylenediamine) (oxidative) Maximum absorption through the skin A (µg/cm2) = 3.6 µg/cm2 Skin Area surface SAS (cm2) = 700 cm2 Dermal absorption per treatment SAS x A x 0.001 = 2.52 mg Typical body weight of human = 60 kg Systemic exposure dose (...","duration":"90 day","effect":"SCCP/0980/06 OPINION ON 4-NITRO-O-PHENYLENEDIAMINE 55 3.3.13. Safety evaluation (including calculation of the MoS) CALCULATION OF THE MARGIN OF SAFETY (4-nitro-o-phenylenediamine) (oxidative) Maximum absorption through the skin A (µg/cm2) = 3.6 µg/cm2 Skin Area surface SAS (cm2) = 700 cm2 Dermal absorption per treatment SAS x A x 0.001 = 2.52 mg Typical body weight of human = 60 kg Systemic exposure dose (SED) SAS x A x 0.001/60 = 0.042 mg/kg No observed adverse effect level NOAEL = 15 mg/kg (rat, oral, 90 day) Margin of Safety NOAEL / SED = 357 3.3.14. Discussion Physico-chemical specifications 4-nitro-o-phenylenediamine is used in oxidative hair dye formulations at a maximum concentration of 0.5%, after mixing with hydrogen peroxide. Stability of 4-nitro-o- phenylenediamine in marketed products is not reported. General toxicity The acute median lethal oral dose of 4-nitro-o-phenylenediamine reported in mice and rats varies from 680 to 2100 mg/kg bw. The majority of the toxico","endpoint":"dermal absorption","ingredient":"was submitted in December 1981 by COLIPA.","loael_value":"","noael_unit":"mg/kg","noael_value":"= 0.042","page":55,"route":"oral","species":"rat","study_id":"sccp_o_093_noael_008"} |
| Regulatory source | dermal absorption | =15 | mg/kg | rat | oral | 90 day | dermal absorption | SOURCE_SUBDIR=sccp_o_093; REPORT_TITLE=OPINION ON 4-NITRO-O-PHENYLENEDIAMINE COLIPA N° B24; OPINION_NUMBER=SCCP/0980/06; COMMITTEE=Scientific Committee on Consumer Products (SCCP); REPORT_DATE=19 December 2006; VALUE_TEXT== 15; DOSE=Safety evaluation (including calculation of the MoS) CALCULATION OF THE MARGIN OF SAFETY (4-nitro-o-phenylenediamine) (oxidative) Maximum absorption through the skin A (µg/cm2) = 3.6 µg/cm2 Skin Area surface SAS (cm2) = 700 cm2 Dermal absorption per treatment SAS x A x 0.001 = 2.52 mg Typical body weight of human = 60 kg Systemic exposure dose (...; EFFECT=SCCP/0980/06 OPINION ON 4-NITRO-O-PHENYLENEDIAMINE 55 3.3.13. Safety evaluation (including calculation of the MoS) CALCULATION OF THE MARGIN OF SAFETY (4-nitro-o-phenylenediamine) (oxidative) Maximum absorption through the skin A (µg/cm2) = 3.6 µg/cm2 Skin Area surface SAS (cm2) = 700 cm2 Dermal absorption per treatment SAS x A x 0.001 = 2.52 mg Typical body weight of human = 60 kg Systemic exposure dose (SED) SAS x A x 0.001/60 = 0.042 mg/kg No observed adverse effect level NOAEL = 15 mg/kg (rat, oral, 90 day) Margin of Safety NOAEL / SED = 357 3.3.14. Discussion Physico-chemical specifications 4-nitro-o-phenylenediamine is used in oxidative hair dye formulations at a maximum concentration of 0.5%, after mixing with hydrogen peroxide. Stability of 4-nitro-o- phenylenediamine in marketed products is not reported. General toxicity The acute median lethal oral dose of 4-nitro-o-phenylenediamine reported in mice and rats varies from 680 to 2100 mg/kg bw. The majority of the toxicology s; CITATION_NUMBERS=[]; DETAILS_JSON={"cas_number":"99-56-9","citation":"","dose":"Safety evaluation (including calculation of the MoS) CALCULATION OF THE MARGIN OF SAFETY (4-nitro-o-phenylenediamine) (oxidative) Maximum absorption through the skin A (µg/cm2) = 3.6 µg/cm2 Skin Area surface SAS (cm2) = 700 cm2 Dermal absorption per treatment SAS x A x 0.001 = 2.52 mg Typical body weight of human = 60 kg Systemic exposure dose (...","duration":"90 day","effect":"SCCP/0980/06 OPINION ON 4-NITRO-O-PHENYLENEDIAMINE 55 3.3.13. Safety evaluation (including calculation of the MoS) CALCULATION OF THE MARGIN OF SAFETY (4-nitro-o-phenylenediamine) (oxidative) Maximum absorption through the skin A (µg/cm2) = 3.6 µg/cm2 Skin Area surface SAS (cm2) = 700 cm2 Dermal absorption per treatment SAS x A x 0.001 = 2.52 mg Typical body weight of human = 60 kg Systemic exposure dose (SED) SAS x A x 0.001/60 = 0.042 mg/kg No observed adverse effect level NOAEL = 15 mg/kg (rat, oral, 90 day) Margin of Safety NOAEL / SED = 357 3.3.14. Discussion Physico-chemical specifications 4-nitro-o-phenylenediamine is used in oxidative hair dye formulations at a maximum concentration of 0.5%, after mixing with hydrogen peroxide. Stability of 4-nitro-o- phenylenediamine in marketed products is not reported. General toxicity The acute median lethal oral dose of 4-nitro-o-phenylenediamine reported in mice and rats varies from 680 to 2100 mg/kg bw. The majority of the toxicology s","endpoint":"dermal absorption","ingredient":"was submitted in December 1981 by COLIPA.","loael_value":"","noael_unit":"mg/kg","noael_value":"= 15","page":55,"route":"oral","species":"rat","study_id":"sccp_o_093_noael_009"} |
| Regulatory source | dermal absorption | =15 | mg/kg | rat | oral | 90 day | dermal absorption | SOURCE_SUBDIR=sccp_o_093; REPORT_TITLE=OPINION ON 4-NITRO-O-PHENYLENEDIAMINE COLIPA N° B24; OPINION_NUMBER=SCCP/0980/06; COMMITTEE=Scientific Committee on Consumer Products (SCCP); REPORT_DATE=19 December 2006; VALUE_TEXT== 15; DOSE=Safety evaluation (including calculation of the MoS) CALCULATION OF THE MARGIN OF SAFETY (4-nitro-o-phenylenediamine) (oxidative) Maximum absorption through the skin A (µg/cm2) = 3.6 µg/cm2 Skin Area surface SAS (cm2) = 700 cm2 Dermal absorption per treatment SAS x A x 0.001 = 2.52 mg Typical body weight of human = 60 kg Systemic exposure dose (...; EFFECT=4-NITRO-O-PHENYLENEDIAMINE 55 3.3.13. Safety evaluation (including calculation of the MoS) CALCULATION OF THE MARGIN OF SAFETY (4-nitro-o-phenylenediamine) (oxidative) Maximum absorption through the skin A (µg/cm2) = 3.6 µg/cm2 Skin Area surface SAS (cm2) = 700 cm2 Dermal absorption per treatment SAS x A x 0.001 = 2.52 mg Typical body weight of human = 60 kg Systemic exposure dose (SED) SAS x A x 0.001/60 = 0.042 mg/kg No observed adverse effect level NOAEL = 15 mg/kg (rat, oral, 90 day) Margin of Safety NOAEL / SED = 357 3.3.14. Discussion Physico-chemical specifications 4-nitro-o-phenylenediamine is used in oxidative hair dye formulations at a maximum concentration of 0.5%, after mixing with hydrogen peroxide. Stability of 4-nitro-o- phenylenediamine in marketed products is not reported. General toxicity The acute median lethal oral dose of 4-nitro-o-phenylenediamine reported in mice and rats varies from 680 to 2100 mg/kg bw. The majority of the toxicology studies is old and not performed under current guidelines; CITATION_NUMBERS=[]; DETAILS_JSON={"cas_number":"99-56-9","citation":"","dose":"Safety evaluation (including calculation of the MoS) CALCULATION OF THE MARGIN OF SAFETY (4-nitro-o-phenylenediamine) (oxidative) Maximum absorption through the skin A (µg/cm2) = 3.6 µg/cm2 Skin Area surface SAS (cm2) = 700 cm2 Dermal absorption per treatment SAS x A x 0.001 = 2.52 mg Typical body weight of human = 60 kg Systemic exposure dose (...","duration":"90 day","effect":"4-NITRO-O-PHENYLENEDIAMINE 55 3.3.13. Safety evaluation (including calculation of the MoS) CALCULATION OF THE MARGIN OF SAFETY (4-nitro-o-phenylenediamine) (oxidative) Maximum absorption through the skin A (µg/cm2) = 3.6 µg/cm2 Skin Area surface SAS (cm2) = 700 cm2 Dermal absorption per treatment SAS x A x 0.001 = 2.52 mg Typical body weight of human = 60 kg Systemic exposure dose (SED) SAS x A x 0.001/60 = 0.042 mg/kg No observed adverse effect level NOAEL = 15 mg/kg (rat, oral, 90 day) Margin of Safety NOAEL / SED = 357 3.3.14. Discussion Physico-chemical specifications 4-nitro-o-phenylenediamine is used in oxidative hair dye formulations at a maximum concentration of 0.5%, after mixing with hydrogen peroxide. Stability of 4-nitro-o- phenylenediamine in marketed products is not reported. General toxicity The acute median lethal oral dose of 4-nitro-o-phenylenediamine reported in mice and rats varies from 680 to 2100 mg/kg bw. The majority of the toxicology studies is old and not performed under current guidelines","endpoint":"dermal absorption","ingredient":"was submitted in December 1981 by COLIPA.","loael_value":"","noael_unit":"mg/kg","noael_value":"= 15","page":55,"route":"oral","species":"rat","study_id":"sccp_o_093_noael_010"} |
| Regulatory source | developmental toxicity | 15 | mg/kg bw/day | rat | oral | 90 day | developmental toxicity | SOURCE_SUBDIR=sccp_o_093; REPORT_TITLE=OPINION ON 4-NITRO-O-PHENYLENEDIAMINE COLIPA N° B24; OPINION_NUMBER=SCCP/0980/06; COMMITTEE=Scientific Committee on Consumer Products (SCCP); REPORT_DATE=19 December 2006; VALUE_TEXT=15; DOSE=General toxicity The acute median lethal oral dose of 4-nitro-o-phenylenediamine reported in mice and rats varies from 680 to 2100 mg/kg bw.; EFFECT=emical specifications 4-nitro-o-phenylenediamine is used in oxidative hair dye formulations at a maximum concentration of 0.5%, after mixing with hydrogen peroxide. Stability of 4-nitro-o- phenylenediamine in marketed products is not reported. General toxicity The acute median lethal oral dose of 4-nitro-o-phenylenediamine reported in mice and rats varies from 680 to 2100 mg/kg bw. The majority of the toxicology studies is old and not performed under current guidelines and GLP. However, in a new 90 day study the NOAEL is relatively low (15 mg/kg bw/day). The studies submitted on reproduction toxicity were publications in open literature and were only of limited use for evaluation. In a teratogenicity study (also publication in open literature) effects on maternal weight gain observed at the lowest observed effect level for teratogenic and embryotoxic effects (265mg/kg/day; NOAEL 128 mg/kg/day) were judged to be equivocal by the applicant. The authors of the publication, however, argued that the effects could be accounted for by; CITATION_NUMBERS=[]; DETAILS_JSON={"cas_number":"99-56-9","citation":"","dose":"General toxicity The acute median lethal oral dose of 4-nitro-o-phenylenediamine reported in mice and rats varies from 680 to 2100 mg/kg bw.","duration":"90 day","effect":"emical specifications 4-nitro-o-phenylenediamine is used in oxidative hair dye formulations at a maximum concentration of 0.5%, after mixing with hydrogen peroxide. Stability of 4-nitro-o- phenylenediamine in marketed products is not reported. General toxicity The acute median lethal oral dose of 4-nitro-o-phenylenediamine reported in mice and rats varies from 680 to 2100 mg/kg bw. The majority of the toxicology studies is old and not performed under current guidelines and GLP. However, in a new 90 day study the NOAEL is relatively low (15 mg/kg bw/day). The studies submitted on reproduction toxicity were publications in open literature and were only of limited use for evaluation. In a teratogenicity study (also publication in open literature) effects on maternal weight gain observed at the lowest observed effect level for teratogenic and embryotoxic effects (265mg/kg/day; NOAEL 128 mg/kg/day) were judged to be equivocal by the applicant. The authors of the publication, however, argued that the effects could be accounted for by","endpoint":"developmental toxicity","ingredient":"was submitted in December 1981 by COLIPA.","loael_value":"","noael_unit":"mg/kg bw/day","noael_value":"15","page":55,"route":"oral","species":"rat","study_id":"sccp_o_093_noael_011"} |
| Regulatory source | developmental toxicity | 265 | mg/kg/day | - | - | 90 day | developmental toxicity | SOURCE_SUBDIR=sccp_o_093; REPORT_TITLE=OPINION ON 4-NITRO-O-PHENYLENEDIAMINE COLIPA N° B24; OPINION_NUMBER=SCCP/0980/06; COMMITTEE=Scientific Committee on Consumer Products (SCCP); REPORT_DATE=19 December 2006; VALUE_TEXT=265; DOSE=However, in a new 90 day study the NOAEL is relatively low (15 mg/kg bw/day).; EFFECT=to 2100 mg/kg bw. The majority of the toxicology studies is old and not performed under current guidelines and GLP. However, in a new 90 day study the NOAEL is relatively low (15 mg/kg bw/day). The studies submitted on reproduction toxicity were publications in open literature and were only of limited use for evaluation. In a teratogenicity study (also publication in open literature) effects on maternal weight gain observed at the lowest observed effect level for teratogenic and embryotoxic effects (265mg/kg/day; NOAEL 128 mg/kg/day) were judged to be equivocal by the applicant. The authors of the publication, however, argued that the effects could be accounted for by the reduction in average foetal weight and concluded that this dose was not toxic to pregnant dams. Since no other measurements of maternal toxicity were conducted, no definite conclusion with respect to the maternal toxic dose could be drawn. Therefore, it can not be ruled out that teratogenic (increased incidence of cleft palate) and embryotoxic (reduced foetal w; CITATION_NUMBERS=[]; DETAILS_JSON={"cas_number":"99-56-9","citation":"","dose":"However, in a new 90 day study the NOAEL is relatively low (15 mg/kg bw/day).","duration":"90 day","effect":"to 2100 mg/kg bw. The majority of the toxicology studies is old and not performed under current guidelines and GLP. However, in a new 90 day study the NOAEL is relatively low (15 mg/kg bw/day). The studies submitted on reproduction toxicity were publications in open literature and were only of limited use for evaluation. In a teratogenicity study (also publication in open literature) effects on maternal weight gain observed at the lowest observed effect level for teratogenic and embryotoxic effects (265mg/kg/day; NOAEL 128 mg/kg/day) were judged to be equivocal by the applicant. The authors of the publication, however, argued that the effects could be accounted for by the reduction in average foetal weight and concluded that this dose was not toxic to pregnant dams. Since no other measurements of maternal toxicity were conducted, no definite conclusion with respect to the maternal toxic dose could be drawn. Therefore, it can not be ruled out that teratogenic (increased incidence of cleft palate) and embryotoxic (reduced foetal w","endpoint":"developmental toxicity","ingredient":"was submitted in December 1981 by COLIPA.","loael_value":"","noael_unit":"mg/kg/day","noael_value":"265","page":55,"route":"","species":"","study_id":"sccp_o_093_noael_012"} |
| Regulatory source | reproductive toxicity | 65 | % | - | oral | 90 day | reproductive toxicity | SOURCE_SUBDIR=sccp_o_093; REPORT_TITLE=OPINION ON 4-NITRO-O-PHENYLENEDIAMINE COLIPA N° B24; OPINION_NUMBER=SCCP/0980/06; COMMITTEE=Scientific Committee on Consumer Products (SCCP); REPORT_DATE=19 December 2006; VALUE_TEXT=65; DOSE=Since no other measurements of maternal toxicity were conducted, no definite conclusion with respect to the maternal toxic dose could be drawn.; EFFECT=egnant dams. Since no other measurements of maternal toxicity were conducted, no definite conclusion with respect to the maternal toxic dose could be drawn. Therefore, it can not be ruled out that teratogenic (increased incidence of cleft palate) and embryotoxic (reduced foetal weight) effects occurred at dose levels which were not toxic to the pregnant dams. There are no indications from the old studies and the new 90 day study that e.g. new developmental and/or reproductive studies will identify a (much) low(er) NOAEL. Therefore, and for ethical reasons the SCCP does not ask for new animal studies. Photo-toxicity 4-Nitro-o-phenylenediamine is considered to have no photo-toxic potential. Toxico-kinetics Following oral administration of 4-nitro-o-phenylenediamine, urine was the major route of excretion. At least 65% of the administered 4-nitro-o-phenylenediamine dose was absorbed; CITATION_NUMBERS=[]; DETAILS_JSON={"cas_number":"99-56-9","citation":"","dose":"Since no other measurements of maternal toxicity were conducted, no definite conclusion with respect to the maternal toxic dose could be drawn.","duration":"90 day","effect":"egnant dams. Since no other measurements of maternal toxicity were conducted, no definite conclusion with respect to the maternal toxic dose could be drawn. Therefore, it can not be ruled out that teratogenic (increased incidence of cleft palate) and embryotoxic (reduced foetal weight) effects occurred at dose levels which were not toxic to the pregnant dams. There are no indications from the old studies and the new 90 day study that e.g. new developmental and/or reproductive studies will identify a (much) low(er) NOAEL. Therefore, and for ethical reasons the SCCP does not ask for new animal studies. Photo-toxicity 4-Nitro-o-phenylenediamine is considered to have no photo-toxic potential. Toxico-kinetics Following oral administration of 4-nitro-o-phenylenediamine, urine was the major route of excretion. At least 65% of the administered 4-nitro-o-phenylenediamine dose was absorbed","endpoint":"reproductive toxicity","ingredient":"was submitted in December 1981 by COLIPA.","loael_value":"","noael_unit":"%","noael_value":"65","page":55,"route":"oral","species":"","study_id":"sccp_o_093_noael_013"} |
openFDA substances 4 endpoints
| Source | Endpoint Type | Value | Unit | Species | Route | Duration | Study Type | Reference |
|---|---|---|---|---|---|---|---|---|
| openFDA substances | FDA UNII substance identifier | 5A9AX7Y0TT | UNII | - | - | - | chemical | {"approval_status":null,"molecular_formula":"C6H7N3O2","source_table":"substance_identifiers_fda","substance_class":"chemical","unii_code":"5A9AX7Y0TT"} |
| openFDA substances | FDA UNII substance identifier | 5A9AX7Y0TT | UNII | - | - | - | chemical | {"approval_status":null,"molecular_formula":"C6H7N3O2","source_table":"substance_identifiers_fda","substance_class":"chemical","unii_code":"5A9AX7Y0TT"} |
| openFDA substances | FDA UNII substance identifier | 5A9AX7Y0TT | UNII | - | - | - | chemical | {"approval_status":null,"molecular_formula":"C6H7N3O2","source_table":"substance_identifiers_fda","substance_class":"chemical","unii_code":"5A9AX7Y0TT"} |
| openFDA substances | FDA UNII substance identifier | 5A9AX7Y0TT | UNII | - | - | - | chemical | {"approval_status":null,"molecular_formula":"C6H7N3O2","source_table":"substance_identifiers_fda","substance_class":"chemical","unii_code":"5A9AX7Y0TT"} |