NOAEL Studies Cosmetic Ingredient

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

CAS: 54381-16-7

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

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COSMOS_DB 2 endpoints
Source Endpoint Type Value Unit Species Route Duration Study Type Reference
COSMOS_DB LOAEL 20 mg/kg bw/day rat oral 6-20 Gestation day Developmental SCCP; Oral (Gavage) Developmental Toxicity Study of GTS03849 in Rats, P&G Study # 2628- 54026, November 1, 2005
COSMOS_DB NOAEL 5 mg/kg bw/day rat oral 6-20 Gestation day Developmental SCCP; Oral (Gavage) Developmental Toxicity Study of GTS03849 in Rats, P&G Study # 2628- 54026, November 1, 2005
SCCS_vision_codex 28 endpoints
Source Endpoint Type Value Unit Species Route Duration Study Type Reference
SCCS_vision_codex NOAEL =5 mg/kg bw/day - - - NOAEL study {"citation":"Ref: 18","dose":"ed clinical observations for surviving animals given 100/25 mg/kg/day included thin appearance, mild tremors, few faeces, and rough hair coat for males and females and ocular fasciculation and swaying gait for females only.","effect":"ed clinical observations for surviving animals given 100/25 mg/kg/day included thin appearance, mild tremors, few faeces, and rough hair coat for males and females and ocular fasciculation and swaying gait for females only. There were no remarkable clinical observations for control animals or animals given 50/5 mg/kg/day. There was a decrease in mean body weights and an increase in kidney weight in animals in the 100/25 mg/kg group. No adverse effects were observed in the 50/5 mg/kg bw/day group, and therefore the NOAEL in this study was 5 mg/kg bw/day. Ref: 18","page":15,"pdf":"sccp_o_065.pdf","row_type":"noael_study","study_id":"sccp_o_065_noael_001"}
SCCS_vision_codex NOAEL =20 mg/kg bw/day - - 91 days carcinogenicity {"citation":"Ref.: 19 3","dose":"Results Up to the highest dose level, no adverse effects were noted after administration of the test substance for 91 days, and therefore the NOAEL in this study was 20 mg/kg bw/day.","effect":"inning after Week 10. Blood and urine samples for haematology, coagulation, clinical chemistry, urinalysis, and urine chemistry were collected at each scheduled sacrifice. At each necropsy, macroscopic observations were recorded, selected organs weighed, and selected tissues collected and preserved. Sperm was collected and analysed for motility, morphology and total counts. Results Up to the highest dose level, no adverse effects were noted after administration of the test substance for 91 days, and therefore the NOAEL in this study was 20 mg/kg bw/day. Comment According to OECD 408, the highest dose level should induce toxicity. Ref.: 19 3.3.5.3. Chronic (> 12 months) toxicity See point 3.3.7. Carcinogenicity 3.3.6. Mutagenicity / Genotoxicity 3.3.6.1. Mutagenicity / Genotoxicity in vitro Bacterial gene mutation assay Guideline: OECD 471 (1997) Species/strain: Salmonella typhimurium TA98, TA100, TA1535, and TA1537, Escherichia coli WP2uvrA(pKM101)","page":16,"pdf":"sccp_o_065.pdf","row_type":"noael_study","study_id":"sccp_o_065_noael_002"}
SCCS_vision_codex NOAEL =5 mg/kg/day human oral developmental developmental toxicity {"citation":"Ref.: 28 Remark Dose selection was based on a range finding study, in which at 40 mg/kg (highest dose tested) slight effects on maternal body weight were observed (ref: 27) 3","dose":"ylenediamine sulfate ____________________________________________________________________________________________ 29 Maternal body weight gains and food consumption were reduced in the 20 and 50 mg/kg/day dosage group during the entire dosage period.","effect":"ylenediamine sulfate ____________________________________________________________________________________________ 29 Maternal body weight gains and food consumption were reduced in the 20 and 50 mg/kg/day dosage group during the entire dosage period. Also gravid uterine weights were reduced in these dose groups. Administration of the test substance did not affect litter observations or cause gross external, soft tissue or skeletal foetal alterations. In this study, the maternal no-observable-adverse-effect-level (NOAEL) was 5 mg/kg/day based on reductions on body weight and feed consumption. The developmental NOAEL was 50 mg/kg/day, since no developmental toxicity was observed up to the highest dose tested. Ref.: 28 Remark Dose selection was based on a range finding study, in which at 40 mg/kg (highest dose tested) slight effects on maternal body weight were observed (ref: 27) 3.3.9. Toxicokinetics No data submitted 3.3.10. Photo-induced toxicity No data submitted 3.3.11. Human data Repeated Insult Patch Test Guideline:","page":29,"pdf":"sccp_o_065.pdf","row_type":"noael_study","study_id":"sccp_o_065_noael_003"}
SCCS_vision_codex NOAEL =50 mg/kg/day human oral developmental developmental toxicity {"citation":"Ref.: 28 Remark Dose selection was based on a range finding study, in which at 40 mg/kg (highest dose tested) slight effects on maternal body weight were observed (ref: 27) 3","dose":"_______________ 29 Maternal body weight gains and food consumption were reduced in the 20 and 50 mg/kg/day dosage group during the entire dosage period.","effect":"_______________ 29 Maternal body weight gains and food consumption were reduced in the 20 and 50 mg/kg/day dosage group during the entire dosage period. Also gravid uterine weights were reduced in these dose groups. Administration of the test substance did not affect litter observations or cause gross external, soft tissue or skeletal foetal alterations. In this study, the maternal no-observable-adverse-effect-level (NOAEL) was 5 mg/kg/day based on reductions on body weight and feed consumption. The developmental NOAEL was 50 mg/kg/day, since no developmental toxicity was observed up to the highest dose tested. Ref.: 28 Remark Dose selection was based on a range finding study, in which at 40 mg/kg (highest dose tested) slight effects on maternal body weight were observed (ref: 27) 3.3.9. Toxicokinetics No data submitted 3.3.10. Photo-induced toxicity No data submitted 3.3.11. Human data Repeated Insult Patch Test Guideline: / Species/strain: human female volunteers Group size: 116 Test substance: N,N-bis(2-hydroxyethyl)-","page":29,"pdf":"sccp_o_065.pdf","row_type":"noael_study","study_id":"sccp_o_065_noael_004"}
SCCS_vision_codex NOAEL =0.003 mg/kg rat oral - dermal absorption {"citation":"Ref.: 16 3","dose":"Safety evaluation (including calculation of the MoS) CALCULATION OF THE MARGIN OF SAFETY (N,N-Bis(2-hydroxyethyl)-p-phenylenediamine sulfate) (Oxidative/permanent) Maximum absorption through the skin A (μg/cm²) = 0.252 µg/cm² Skin Area surface SAS (cm²) = 700 cm² Dermal absorption per treatment SAS x A x 0.001 = 0.1764 mg Typical body weight of...","effect":"d was performed in 1984. Ref.: 16 3.3.12. Special investigations See point 3.3.7. 3.3.13. Safety evaluation (including calculation of the MoS) CALCULATION OF THE MARGIN OF SAFETY (N,N-Bis(2-hydroxyethyl)-p-phenylenediamine sulfate) (Oxidative/permanent) Maximum absorption through the skin A (μg/cm²) = 0.252 µg/cm² Skin Area surface SAS (cm²) = 700 cm² Dermal absorption per treatment SAS x A x 0.001 = 0.1764 mg Typical body weight of human = 60 kg Systemic exposure dose (SED) SAS x A x 0.001/60 = 0.003 mg/kg No observed adverse effect level (mg/kg) NOAEL = 5 mg/kg (rat, oral, maternal toxicity) Margin of Safety NOAEL/SED = 1667 3.3.14. Discussion Physico-chemical specification N,N-bis(2-hydroxyethyl)-p-phenylenediamine is a tertiary amine, and thus, it is prone to nitrosation. The substance should not be used in combination with nitrosating agents. Stability of N,N-Bis(2-hydroxyethyl)-p-phenylenediamine is marketed products is not reported. The physico- chemical characterisation and purity of the substance is not reported in several studies. Ge","page":30,"pdf":"sccp_o_065.pdf","row_type":"noael_study","study_id":"sccp_o_065_noael_005"}
SCCS_vision_codex NOAEL =5 mg/kg rat oral - dermal absorption {"dose":"Safety evaluation (including calculation of the MoS) CALCULATION OF THE MARGIN OF SAFETY (N,N-Bis(2-hydroxyethyl)-p-phenylenediamine sulfate) (Oxidative/permanent) Maximum absorption through the skin A (μg/cm²) = 0.252 µg/cm² Skin Area surface SAS (cm²) = 700 cm² Dermal absorption per treatment SAS x A x 0.001 = 0.1764 mg Typical body weight of...","effect":". Special investigations See point 3.3.7. 3.3.13. Safety evaluation (including calculation of the MoS) CALCULATION OF THE MARGIN OF SAFETY (N,N-Bis(2-hydroxyethyl)-p-phenylenediamine sulfate) (Oxidative/permanent) Maximum absorption through the skin A (μg/cm²) = 0.252 µg/cm² Skin Area surface SAS (cm²) = 700 cm² Dermal absorption per treatment SAS x A x 0.001 = 0.1764 mg Typical body weight of human = 60 kg Systemic exposure dose (SED) SAS x A x 0.001/60 = 0.003 mg/kg No observed adverse effect level (mg/kg) NOAEL = 5 mg/kg (rat, oral, maternal toxicity) Margin of Safety NOAEL/SED = 1667 3.3.14. Discussion Physico-chemical specification N,N-bis(2-hydroxyethyl)-p-phenylenediamine is a tertiary amine, and thus, it is prone to nitrosation. The substance should not be used in combination with nitrosating agents. Stability of N,N-Bis(2-hydroxyethyl)-p-phenylenediamine is marketed products is not reported. The physico- chemical characterisation and purity of the substance is not reported in several studies. General toxicity","page":30,"pdf":"sccp_o_065.pdf","row_type":"noael_study","study_id":"sccp_o_065_noael_006"}
SCCS_vision_codex NOAEL =31 mg/kg bw - oral 14 day developmental toxicity {"dose":"General toxicity The oral LD50 in 2 (non-guideline) studies after oral administration ranged between 100 and 400 mg/kg bw.","effect":"tertiary amine, and thus, it is prone to nitrosation. The substance should not be used in combination with nitrosating agents. Stability of N,N-Bis(2-hydroxyethyl)-p-phenylenediamine is marketed products is not reported. The physico- chemical characterisation and purity of the substance is not reported in several studies. General toxicity The oral LD50 in 2 (non-guideline) studies after oral administration ranged between 100 and 400 mg/kg bw. After i.p. administration the LD50 was between 16 and 31 mg/kg bw. The NOAEL was set at 5 mg/kg bw/day (14 day range-finding study) and at 20 mg/kg bw/day (90 day study). The maternal NOAEL was 5 mg/kg/day; the developmental NOAEL was 50 mg/kg/day. The NOAEL from maternal toxicity will be used for the calculation of margin of safety. Irritation / sensitisation Most of the studies are old and not complying with GLP. Presentation of four of the studies is inadequate, among which 1 is unreadable. N,N-bis(2-hydroxyethyl)-p-phenylenediamine sulphate was found to be irritant to mucous membrane.","page":30,"pdf":"sccp_o_065.pdf","row_type":"noael_study","study_id":"sccp_o_065_noael_008"}
SCCS_vision_codex NOAEL =5 mg/kg bw/day - - - NOAEL study {"citation":"Ref: 18","dose":"ed clinical observations for surviving animals given 100/25 mg/kg/day included thin appearance, mild tremors, few faeces, and rough hair coat for males and females and ocular fasciculation and swaying gait for females only.","effect":"ed clinical observations for surviving animals given 100/25 mg/kg/day included thin appearance, mild tremors, few faeces, and rough hair coat for males and females and ocular fasciculation and swaying gait for females only. There were no remarkable clinical observations for control animals or animals given 50/5 mg/kg/day. There was a decrease in mean body weights and an increase in kidney weight in animals in the 100/25 mg/kg group. No adverse effects were observed in the 50/5 mg/kg bw/day group, and therefore the NOAEL in this study was 5 mg/kg bw/day. Ref: 18","page":15,"pdf":"sccp_o_065.pdf","row_type":"noael_study","study_id":"sccp_o_065_noael_001"}
SCCS_vision_codex NOAEL =20 mg/kg bw/day - - 91 days carcinogenicity {"citation":"Ref.: 19 3","dose":"Results Up to the highest dose level, no adverse effects were noted after administration of the test substance for 91 days, and therefore the NOAEL in this study was 20 mg/kg bw/day.","effect":"inning after Week 10. Blood and urine samples for haematology, coagulation, clinical chemistry, urinalysis, and urine chemistry were collected at each scheduled sacrifice. At each necropsy, macroscopic observations were recorded, selected organs weighed, and selected tissues collected and preserved. Sperm was collected and analysed for motility, morphology and total counts. Results Up to the highest dose level, no adverse effects were noted after administration of the test substance for 91 days, and therefore the NOAEL in this study was 20 mg/kg bw/day. Comment According to OECD 408, the highest dose level should induce toxicity. Ref.: 19 3.3.5.3. Chronic (> 12 months) toxicity See point 3.3.7. Carcinogenicity 3.3.6. Mutagenicity / Genotoxicity 3.3.6.1. Mutagenicity / Genotoxicity in vitro Bacterial gene mutation assay Guideline: OECD 471 (1997) Species/strain: Salmonella typhimurium TA98, TA100, TA1535, and TA1537, Escherichia coli WP2uvrA(pKM101)","page":16,"pdf":"sccp_o_065.pdf","row_type":"noael_study","study_id":"sccp_o_065_noael_002"}
SCCS_vision_codex NOAEL =5 mg/kg/day human oral developmental developmental toxicity {"citation":"Ref.: 28 Remark Dose selection was based on a range finding study, in which at 40 mg/kg (highest dose tested) slight effects on maternal body weight were observed (ref: 27) 3","dose":"ylenediamine sulfate ____________________________________________________________________________________________ 29 Maternal body weight gains and food consumption were reduced in the 20 and 50 mg/kg/day dosage group during the entire dosage period.","effect":"ylenediamine sulfate ____________________________________________________________________________________________ 29 Maternal body weight gains and food consumption were reduced in the 20 and 50 mg/kg/day dosage group during the entire dosage period. Also gravid uterine weights were reduced in these dose groups. Administration of the test substance did not affect litter observations or cause gross external, soft tissue or skeletal foetal alterations. In this study, the maternal no-observable-adverse-effect-level (NOAEL) was 5 mg/kg/day based on reductions on body weight and feed consumption. The developmental NOAEL was 50 mg/kg/day, since no developmental toxicity was observed up to the highest dose tested. Ref.: 28 Remark Dose selection was based on a range finding study, in which at 40 mg/kg (highest dose tested) slight effects on maternal body weight were observed (ref: 27) 3.3.9. Toxicokinetics No data submitted 3.3.10. Photo-induced toxicity No data submitted 3.3.11. Human data Repeated Insult Patch Test Guideline:","page":29,"pdf":"sccp_o_065.pdf","row_type":"noael_study","study_id":"sccp_o_065_noael_003"}
SCCS_vision_codex NOAEL =50 mg/kg/day human oral developmental developmental toxicity {"citation":"Ref.: 28 Remark Dose selection was based on a range finding study, in which at 40 mg/kg (highest dose tested) slight effects on maternal body weight were observed (ref: 27) 3","dose":"_______________ 29 Maternal body weight gains and food consumption were reduced in the 20 and 50 mg/kg/day dosage group during the entire dosage period.","effect":"_______________ 29 Maternal body weight gains and food consumption were reduced in the 20 and 50 mg/kg/day dosage group during the entire dosage period. Also gravid uterine weights were reduced in these dose groups. Administration of the test substance did not affect litter observations or cause gross external, soft tissue or skeletal foetal alterations. In this study, the maternal no-observable-adverse-effect-level (NOAEL) was 5 mg/kg/day based on reductions on body weight and feed consumption. The developmental NOAEL was 50 mg/kg/day, since no developmental toxicity was observed up to the highest dose tested. Ref.: 28 Remark Dose selection was based on a range finding study, in which at 40 mg/kg (highest dose tested) slight effects on maternal body weight were observed (ref: 27) 3.3.9. Toxicokinetics No data submitted 3.3.10. Photo-induced toxicity No data submitted 3.3.11. Human data Repeated Insult Patch Test Guideline: / Species/strain: human female volunteers Group size: 116 Test substance: N,N-bis(2-hydroxyethyl)-","page":29,"pdf":"sccp_o_065.pdf","row_type":"noael_study","study_id":"sccp_o_065_noael_004"}
SCCS_vision_codex NOAEL =0.003 mg/kg rat oral - dermal absorption {"citation":"Ref.: 16 3","dose":"Safety evaluation (including calculation of the MoS) CALCULATION OF THE MARGIN OF SAFETY (N,N-Bis(2-hydroxyethyl)-p-phenylenediamine sulfate) (Oxidative/permanent) Maximum absorption through the skin A (μg/cm²) = 0.252 µg/cm² Skin Area surface SAS (cm²) = 700 cm² Dermal absorption per treatment SAS x A x 0.001 = 0.1764 mg Typical body weight of...","effect":"d was performed in 1984. Ref.: 16 3.3.12. Special investigations See point 3.3.7. 3.3.13. Safety evaluation (including calculation of the MoS) CALCULATION OF THE MARGIN OF SAFETY (N,N-Bis(2-hydroxyethyl)-p-phenylenediamine sulfate) (Oxidative/permanent) Maximum absorption through the skin A (μg/cm²) = 0.252 µg/cm² Skin Area surface SAS (cm²) = 700 cm² Dermal absorption per treatment SAS x A x 0.001 = 0.1764 mg Typical body weight of human = 60 kg Systemic exposure dose (SED) SAS x A x 0.001/60 = 0.003 mg/kg No observed adverse effect level (mg/kg) NOAEL = 5 mg/kg (rat, oral, maternal toxicity) Margin of Safety NOAEL/SED = 1667 3.3.14. Discussion Physico-chemical specification N,N-bis(2-hydroxyethyl)-p-phenylenediamine is a tertiary amine, and thus, it is prone to nitrosation. The substance should not be used in combination with nitrosating agents. Stability of N,N-Bis(2-hydroxyethyl)-p-phenylenediamine is marketed products is not reported. The physico- chemical characterisation and purity of the substance is not reported in several studies. Ge","page":30,"pdf":"sccp_o_065.pdf","row_type":"noael_study","study_id":"sccp_o_065_noael_005"}
SCCS_vision_codex NOAEL =5 mg/kg rat oral - dermal absorption {"dose":"Safety evaluation (including calculation of the MoS) CALCULATION OF THE MARGIN OF SAFETY (N,N-Bis(2-hydroxyethyl)-p-phenylenediamine sulfate) (Oxidative/permanent) Maximum absorption through the skin A (μg/cm²) = 0.252 µg/cm² Skin Area surface SAS (cm²) = 700 cm² Dermal absorption per treatment SAS x A x 0.001 = 0.1764 mg Typical body weight of...","effect":". Special investigations See point 3.3.7. 3.3.13. Safety evaluation (including calculation of the MoS) CALCULATION OF THE MARGIN OF SAFETY (N,N-Bis(2-hydroxyethyl)-p-phenylenediamine sulfate) (Oxidative/permanent) Maximum absorption through the skin A (μg/cm²) = 0.252 µg/cm² Skin Area surface SAS (cm²) = 700 cm² Dermal absorption per treatment SAS x A x 0.001 = 0.1764 mg Typical body weight of human = 60 kg Systemic exposure dose (SED) SAS x A x 0.001/60 = 0.003 mg/kg No observed adverse effect level (mg/kg) NOAEL = 5 mg/kg (rat, oral, maternal toxicity) Margin of Safety NOAEL/SED = 1667 3.3.14. Discussion Physico-chemical specification N,N-bis(2-hydroxyethyl)-p-phenylenediamine is a tertiary amine, and thus, it is prone to nitrosation. The substance should not be used in combination with nitrosating agents. Stability of N,N-Bis(2-hydroxyethyl)-p-phenylenediamine is marketed products is not reported. The physico- chemical characterisation and purity of the substance is not reported in several studies. General toxicity","page":30,"pdf":"sccp_o_065.pdf","row_type":"noael_study","study_id":"sccp_o_065_noael_006"}
SCCS_vision_codex NOAEL =31 mg/kg bw - oral 14 day developmental toxicity {"dose":"General toxicity The oral LD50 in 2 (non-guideline) studies after oral administration ranged between 100 and 400 mg/kg bw.","effect":"tertiary amine, and thus, it is prone to nitrosation. The substance should not be used in combination with nitrosating agents. Stability of N,N-Bis(2-hydroxyethyl)-p-phenylenediamine is marketed products is not reported. The physico- chemical characterisation and purity of the substance is not reported in several studies. General toxicity The oral LD50 in 2 (non-guideline) studies after oral administration ranged between 100 and 400 mg/kg bw. After i.p. administration the LD50 was between 16 and 31 mg/kg bw. The NOAEL was set at 5 mg/kg bw/day (14 day range-finding study) and at 20 mg/kg bw/day (90 day study). The maternal NOAEL was 5 mg/kg/day; the developmental NOAEL was 50 mg/kg/day. The NOAEL from maternal toxicity will be used for the calculation of margin of safety. Irritation / sensitisation Most of the studies are old and not complying with GLP. Presentation of four of the studies is inadequate, among which 1 is unreadable. N,N-bis(2-hydroxyethyl)-p-phenylenediamine sulphate was found to be irritant to mucous membrane.","page":30,"pdf":"sccp_o_065.pdf","row_type":"noael_study","study_id":"sccp_o_065_noael_008"}
SCCS_vision_codex NOAEL =5 mg/kg bw/day - - - NOAEL study {"citation":"Ref: 18","dose":"ed clinical observations for surviving animals given 100/25 mg/kg/day included thin appearance, mild tremors, few faeces, and rough hair coat for males and females and ocular fasciculation and swaying gait for females only.","effect":"ed clinical observations for surviving animals given 100/25 mg/kg/day included thin appearance, mild tremors, few faeces, and rough hair coat for males and females and ocular fasciculation and swaying gait for females only. There were no remarkable clinical observations for control animals or animals given 50/5 mg/kg/day. There was a decrease in mean body weights and an increase in kidney weight in animals in the 100/25 mg/kg group. No adverse effects were observed in the 50/5 mg/kg bw/day group, and therefore the NOAEL in this study was 5 mg/kg bw/day. Ref: 18","page":15,"pdf":"sccp_o_065.pdf","row_type":"noael_study","study_id":"sccp_o_065_noael_001"}
SCCS_vision_codex NOAEL =20 mg/kg bw/day - - 91 days carcinogenicity {"citation":"Ref.: 19 3","dose":"Results Up to the highest dose level, no adverse effects were noted after administration of the test substance for 91 days, and therefore the NOAEL in this study was 20 mg/kg bw/day.","effect":"inning after Week 10. Blood and urine samples for haematology, coagulation, clinical chemistry, urinalysis, and urine chemistry were collected at each scheduled sacrifice. At each necropsy, macroscopic observations were recorded, selected organs weighed, and selected tissues collected and preserved. Sperm was collected and analysed for motility, morphology and total counts. Results Up to the highest dose level, no adverse effects were noted after administration of the test substance for 91 days, and therefore the NOAEL in this study was 20 mg/kg bw/day. Comment According to OECD 408, the highest dose level should induce toxicity. Ref.: 19 3.3.5.3. Chronic (> 12 months) toxicity See point 3.3.7. Carcinogenicity 3.3.6. Mutagenicity / Genotoxicity 3.3.6.1. Mutagenicity / Genotoxicity in vitro Bacterial gene mutation assay Guideline: OECD 471 (1997) Species/strain: Salmonella typhimurium TA98, TA100, TA1535, and TA1537, Escherichia coli WP2uvrA(pKM101)","page":16,"pdf":"sccp_o_065.pdf","row_type":"noael_study","study_id":"sccp_o_065_noael_002"}
SCCS_vision_codex NOAEL =5 mg/kg/day human oral developmental developmental toxicity {"citation":"Ref.: 28 Remark Dose selection was based on a range finding study, in which at 40 mg/kg (highest dose tested) slight effects on maternal body weight were observed (ref: 27) 3","dose":"ylenediamine sulfate ____________________________________________________________________________________________ 29 Maternal body weight gains and food consumption were reduced in the 20 and 50 mg/kg/day dosage group during the entire dosage period.","effect":"ylenediamine sulfate ____________________________________________________________________________________________ 29 Maternal body weight gains and food consumption were reduced in the 20 and 50 mg/kg/day dosage group during the entire dosage period. Also gravid uterine weights were reduced in these dose groups. Administration of the test substance did not affect litter observations or cause gross external, soft tissue or skeletal foetal alterations. In this study, the maternal no-observable-adverse-effect-level (NOAEL) was 5 mg/kg/day based on reductions on body weight and feed consumption. The developmental NOAEL was 50 mg/kg/day, since no developmental toxicity was observed up to the highest dose tested. Ref.: 28 Remark Dose selection was based on a range finding study, in which at 40 mg/kg (highest dose tested) slight effects on maternal body weight were observed (ref: 27) 3.3.9. Toxicokinetics No data submitted 3.3.10. Photo-induced toxicity No data submitted 3.3.11. Human data Repeated Insult Patch Test Guideline:","page":29,"pdf":"sccp_o_065.pdf","row_type":"noael_study","study_id":"sccp_o_065_noael_003"}
SCCS_vision_codex NOAEL =50 mg/kg/day human oral developmental developmental toxicity {"citation":"Ref.: 28 Remark Dose selection was based on a range finding study, in which at 40 mg/kg (highest dose tested) slight effects on maternal body weight were observed (ref: 27) 3","dose":"_______________ 29 Maternal body weight gains and food consumption were reduced in the 20 and 50 mg/kg/day dosage group during the entire dosage period.","effect":"_______________ 29 Maternal body weight gains and food consumption were reduced in the 20 and 50 mg/kg/day dosage group during the entire dosage period. Also gravid uterine weights were reduced in these dose groups. Administration of the test substance did not affect litter observations or cause gross external, soft tissue or skeletal foetal alterations. In this study, the maternal no-observable-adverse-effect-level (NOAEL) was 5 mg/kg/day based on reductions on body weight and feed consumption. The developmental NOAEL was 50 mg/kg/day, since no developmental toxicity was observed up to the highest dose tested. Ref.: 28 Remark Dose selection was based on a range finding study, in which at 40 mg/kg (highest dose tested) slight effects on maternal body weight were observed (ref: 27) 3.3.9. Toxicokinetics No data submitted 3.3.10. Photo-induced toxicity No data submitted 3.3.11. Human data Repeated Insult Patch Test Guideline: / Species/strain: human female volunteers Group size: 116 Test substance: N,N-bis(2-hydroxyethyl)-","page":29,"pdf":"sccp_o_065.pdf","row_type":"noael_study","study_id":"sccp_o_065_noael_004"}
SCCS_vision_codex NOAEL =0.003 mg/kg rat oral - dermal absorption {"citation":"Ref.: 16 3","dose":"Safety evaluation (including calculation of the MoS) CALCULATION OF THE MARGIN OF SAFETY (N,N-Bis(2-hydroxyethyl)-p-phenylenediamine sulfate) (Oxidative/permanent) Maximum absorption through the skin A (μg/cm²) = 0.252 µg/cm² Skin Area surface SAS (cm²) = 700 cm² Dermal absorption per treatment SAS x A x 0.001 = 0.1764 mg Typical body weight of...","effect":"d was performed in 1984. Ref.: 16 3.3.12. Special investigations See point 3.3.7. 3.3.13. Safety evaluation (including calculation of the MoS) CALCULATION OF THE MARGIN OF SAFETY (N,N-Bis(2-hydroxyethyl)-p-phenylenediamine sulfate) (Oxidative/permanent) Maximum absorption through the skin A (μg/cm²) = 0.252 µg/cm² Skin Area surface SAS (cm²) = 700 cm² Dermal absorption per treatment SAS x A x 0.001 = 0.1764 mg Typical body weight of human = 60 kg Systemic exposure dose (SED) SAS x A x 0.001/60 = 0.003 mg/kg No observed adverse effect level (mg/kg) NOAEL = 5 mg/kg (rat, oral, maternal toxicity) Margin of Safety NOAEL/SED = 1667 3.3.14. Discussion Physico-chemical specification N,N-bis(2-hydroxyethyl)-p-phenylenediamine is a tertiary amine, and thus, it is prone to nitrosation. The substance should not be used in combination with nitrosating agents. Stability of N,N-Bis(2-hydroxyethyl)-p-phenylenediamine is marketed products is not reported. The physico- chemical characterisation and purity of the substance is not reported in several studies. Ge","page":30,"pdf":"sccp_o_065.pdf","row_type":"noael_study","study_id":"sccp_o_065_noael_005"}
SCCS_vision_codex NOAEL =5 mg/kg rat oral - dermal absorption {"dose":"Safety evaluation (including calculation of the MoS) CALCULATION OF THE MARGIN OF SAFETY (N,N-Bis(2-hydroxyethyl)-p-phenylenediamine sulfate) (Oxidative/permanent) Maximum absorption through the skin A (μg/cm²) = 0.252 µg/cm² Skin Area surface SAS (cm²) = 700 cm² Dermal absorption per treatment SAS x A x 0.001 = 0.1764 mg Typical body weight of...","effect":". Special investigations See point 3.3.7. 3.3.13. Safety evaluation (including calculation of the MoS) CALCULATION OF THE MARGIN OF SAFETY (N,N-Bis(2-hydroxyethyl)-p-phenylenediamine sulfate) (Oxidative/permanent) Maximum absorption through the skin A (μg/cm²) = 0.252 µg/cm² Skin Area surface SAS (cm²) = 700 cm² Dermal absorption per treatment SAS x A x 0.001 = 0.1764 mg Typical body weight of human = 60 kg Systemic exposure dose (SED) SAS x A x 0.001/60 = 0.003 mg/kg No observed adverse effect level (mg/kg) NOAEL = 5 mg/kg (rat, oral, maternal toxicity) Margin of Safety NOAEL/SED = 1667 3.3.14. Discussion Physico-chemical specification N,N-bis(2-hydroxyethyl)-p-phenylenediamine is a tertiary amine, and thus, it is prone to nitrosation. The substance should not be used in combination with nitrosating agents. Stability of N,N-Bis(2-hydroxyethyl)-p-phenylenediamine is marketed products is not reported. The physico- chemical characterisation and purity of the substance is not reported in several studies. General toxicity","page":30,"pdf":"sccp_o_065.pdf","row_type":"noael_study","study_id":"sccp_o_065_noael_006"}
SCCS_vision_codex NOAEL =31 mg/kg bw - oral 14 day developmental toxicity {"dose":"General toxicity The oral LD50 in 2 (non-guideline) studies after oral administration ranged between 100 and 400 mg/kg bw.","effect":"tertiary amine, and thus, it is prone to nitrosation. The substance should not be used in combination with nitrosating agents. Stability of N,N-Bis(2-hydroxyethyl)-p-phenylenediamine is marketed products is not reported. The physico- chemical characterisation and purity of the substance is not reported in several studies. General toxicity The oral LD50 in 2 (non-guideline) studies after oral administration ranged between 100 and 400 mg/kg bw. After i.p. administration the LD50 was between 16 and 31 mg/kg bw. The NOAEL was set at 5 mg/kg bw/day (14 day range-finding study) and at 20 mg/kg bw/day (90 day study). The maternal NOAEL was 5 mg/kg/day; the developmental NOAEL was 50 mg/kg/day. The NOAEL from maternal toxicity will be used for the calculation of margin of safety. Irritation / sensitisation Most of the studies are old and not complying with GLP. Presentation of four of the studies is inadequate, among which 1 is unreadable. N,N-bis(2-hydroxyethyl)-p-phenylenediamine sulphate was found to be irritant to mucous membrane.","page":30,"pdf":"sccp_o_065.pdf","row_type":"noael_study","study_id":"sccp_o_065_noael_008"}
SCCS_vision_codex NOAEL =5 mg/kg bw/day - - - NOAEL study {"citation":"Ref: 18","dose":"ed clinical observations for surviving animals given 100/25 mg/kg/day included thin appearance, mild tremors, few faeces, and rough hair coat for males and females and ocular fasciculation and swaying gait for females only.","effect":"ed clinical observations for surviving animals given 100/25 mg/kg/day included thin appearance, mild tremors, few faeces, and rough hair coat for males and females and ocular fasciculation and swaying gait for females only. There were no remarkable clinical observations for control animals or animals given 50/5 mg/kg/day. There was a decrease in mean body weights and an increase in kidney weight in animals in the 100/25 mg/kg group. No adverse effects were observed in the 50/5 mg/kg bw/day group, and therefore the NOAEL in this study was 5 mg/kg bw/day. Ref: 18","page":15,"pdf":"sccp_o_065.pdf","row_type":"noael_study","study_id":"sccp_o_065_noael_001"}
SCCS_vision_codex NOAEL =20 mg/kg bw/day - - 91 days carcinogenicity {"citation":"Ref.: 19 3","dose":"Results Up to the highest dose level, no adverse effects were noted after administration of the test substance for 91 days, and therefore the NOAEL in this study was 20 mg/kg bw/day.","effect":"inning after Week 10. Blood and urine samples for haematology, coagulation, clinical chemistry, urinalysis, and urine chemistry were collected at each scheduled sacrifice. At each necropsy, macroscopic observations were recorded, selected organs weighed, and selected tissues collected and preserved. Sperm was collected and analysed for motility, morphology and total counts. Results Up to the highest dose level, no adverse effects were noted after administration of the test substance for 91 days, and therefore the NOAEL in this study was 20 mg/kg bw/day. Comment According to OECD 408, the highest dose level should induce toxicity. Ref.: 19 3.3.5.3. Chronic (> 12 months) toxicity See point 3.3.7. Carcinogenicity 3.3.6. Mutagenicity / Genotoxicity 3.3.6.1. Mutagenicity / Genotoxicity in vitro Bacterial gene mutation assay Guideline: OECD 471 (1997) Species/strain: Salmonella typhimurium TA98, TA100, TA1535, and TA1537, Escherichia coli WP2uvrA(pKM101)","page":16,"pdf":"sccp_o_065.pdf","row_type":"noael_study","study_id":"sccp_o_065_noael_002"}
SCCS_vision_codex NOAEL =5 mg/kg/day human oral developmental developmental toxicity {"citation":"Ref.: 28 Remark Dose selection was based on a range finding study, in which at 40 mg/kg (highest dose tested) slight effects on maternal body weight were observed (ref: 27) 3","dose":"ylenediamine sulfate ____________________________________________________________________________________________ 29 Maternal body weight gains and food consumption were reduced in the 20 and 50 mg/kg/day dosage group during the entire dosage period.","effect":"ylenediamine sulfate ____________________________________________________________________________________________ 29 Maternal body weight gains and food consumption were reduced in the 20 and 50 mg/kg/day dosage group during the entire dosage period. Also gravid uterine weights were reduced in these dose groups. Administration of the test substance did not affect litter observations or cause gross external, soft tissue or skeletal foetal alterations. In this study, the maternal no-observable-adverse-effect-level (NOAEL) was 5 mg/kg/day based on reductions on body weight and feed consumption. The developmental NOAEL was 50 mg/kg/day, since no developmental toxicity was observed up to the highest dose tested. Ref.: 28 Remark Dose selection was based on a range finding study, in which at 40 mg/kg (highest dose tested) slight effects on maternal body weight were observed (ref: 27) 3.3.9. Toxicokinetics No data submitted 3.3.10. Photo-induced toxicity No data submitted 3.3.11. Human data Repeated Insult Patch Test Guideline:","page":29,"pdf":"sccp_o_065.pdf","row_type":"noael_study","study_id":"sccp_o_065_noael_003"}
SCCS_vision_codex NOAEL =50 mg/kg/day human oral developmental developmental toxicity {"citation":"Ref.: 28 Remark Dose selection was based on a range finding study, in which at 40 mg/kg (highest dose tested) slight effects on maternal body weight were observed (ref: 27) 3","dose":"_______________ 29 Maternal body weight gains and food consumption were reduced in the 20 and 50 mg/kg/day dosage group during the entire dosage period.","effect":"_______________ 29 Maternal body weight gains and food consumption were reduced in the 20 and 50 mg/kg/day dosage group during the entire dosage period. Also gravid uterine weights were reduced in these dose groups. Administration of the test substance did not affect litter observations or cause gross external, soft tissue or skeletal foetal alterations. In this study, the maternal no-observable-adverse-effect-level (NOAEL) was 5 mg/kg/day based on reductions on body weight and feed consumption. The developmental NOAEL was 50 mg/kg/day, since no developmental toxicity was observed up to the highest dose tested. Ref.: 28 Remark Dose selection was based on a range finding study, in which at 40 mg/kg (highest dose tested) slight effects on maternal body weight were observed (ref: 27) 3.3.9. Toxicokinetics No data submitted 3.3.10. Photo-induced toxicity No data submitted 3.3.11. Human data Repeated Insult Patch Test Guideline: / Species/strain: human female volunteers Group size: 116 Test substance: N,N-bis(2-hydroxyethyl)-","page":29,"pdf":"sccp_o_065.pdf","row_type":"noael_study","study_id":"sccp_o_065_noael_004"}
SCCS_vision_codex NOAEL =0.003 mg/kg rat oral - dermal absorption {"citation":"Ref.: 16 3","dose":"Safety evaluation (including calculation of the MoS) CALCULATION OF THE MARGIN OF SAFETY (N,N-Bis(2-hydroxyethyl)-p-phenylenediamine sulfate) (Oxidative/permanent) Maximum absorption through the skin A (μg/cm²) = 0.252 µg/cm² Skin Area surface SAS (cm²) = 700 cm² Dermal absorption per treatment SAS x A x 0.001 = 0.1764 mg Typical body weight of...","effect":"d was performed in 1984. Ref.: 16 3.3.12. Special investigations See point 3.3.7. 3.3.13. Safety evaluation (including calculation of the MoS) CALCULATION OF THE MARGIN OF SAFETY (N,N-Bis(2-hydroxyethyl)-p-phenylenediamine sulfate) (Oxidative/permanent) Maximum absorption through the skin A (μg/cm²) = 0.252 µg/cm² Skin Area surface SAS (cm²) = 700 cm² Dermal absorption per treatment SAS x A x 0.001 = 0.1764 mg Typical body weight of human = 60 kg Systemic exposure dose (SED) SAS x A x 0.001/60 = 0.003 mg/kg No observed adverse effect level (mg/kg) NOAEL = 5 mg/kg (rat, oral, maternal toxicity) Margin of Safety NOAEL/SED = 1667 3.3.14. Discussion Physico-chemical specification N,N-bis(2-hydroxyethyl)-p-phenylenediamine is a tertiary amine, and thus, it is prone to nitrosation. The substance should not be used in combination with nitrosating agents. Stability of N,N-Bis(2-hydroxyethyl)-p-phenylenediamine is marketed products is not reported. The physico- chemical characterisation and purity of the substance is not reported in several studies. Ge","page":30,"pdf":"sccp_o_065.pdf","row_type":"noael_study","study_id":"sccp_o_065_noael_005"}
SCCS_vision_codex NOAEL =5 mg/kg rat oral - dermal absorption {"dose":"Safety evaluation (including calculation of the MoS) CALCULATION OF THE MARGIN OF SAFETY (N,N-Bis(2-hydroxyethyl)-p-phenylenediamine sulfate) (Oxidative/permanent) Maximum absorption through the skin A (μg/cm²) = 0.252 µg/cm² Skin Area surface SAS (cm²) = 700 cm² Dermal absorption per treatment SAS x A x 0.001 = 0.1764 mg Typical body weight of...","effect":". Special investigations See point 3.3.7. 3.3.13. Safety evaluation (including calculation of the MoS) CALCULATION OF THE MARGIN OF SAFETY (N,N-Bis(2-hydroxyethyl)-p-phenylenediamine sulfate) (Oxidative/permanent) Maximum absorption through the skin A (μg/cm²) = 0.252 µg/cm² Skin Area surface SAS (cm²) = 700 cm² Dermal absorption per treatment SAS x A x 0.001 = 0.1764 mg Typical body weight of human = 60 kg Systemic exposure dose (SED) SAS x A x 0.001/60 = 0.003 mg/kg No observed adverse effect level (mg/kg) NOAEL = 5 mg/kg (rat, oral, maternal toxicity) Margin of Safety NOAEL/SED = 1667 3.3.14. Discussion Physico-chemical specification N,N-bis(2-hydroxyethyl)-p-phenylenediamine is a tertiary amine, and thus, it is prone to nitrosation. The substance should not be used in combination with nitrosating agents. Stability of N,N-Bis(2-hydroxyethyl)-p-phenylenediamine is marketed products is not reported. The physico- chemical characterisation and purity of the substance is not reported in several studies. General toxicity","page":30,"pdf":"sccp_o_065.pdf","row_type":"noael_study","study_id":"sccp_o_065_noael_006"}
SCCS_vision_codex NOAEL =31 mg/kg bw - oral 14 day developmental toxicity {"dose":"General toxicity The oral LD50 in 2 (non-guideline) studies after oral administration ranged between 100 and 400 mg/kg bw.","effect":"tertiary amine, and thus, it is prone to nitrosation. The substance should not be used in combination with nitrosating agents. Stability of N,N-Bis(2-hydroxyethyl)-p-phenylenediamine is marketed products is not reported. The physico- chemical characterisation and purity of the substance is not reported in several studies. General toxicity The oral LD50 in 2 (non-guideline) studies after oral administration ranged between 100 and 400 mg/kg bw. After i.p. administration the LD50 was between 16 and 31 mg/kg bw. The NOAEL was set at 5 mg/kg bw/day (14 day range-finding study) and at 20 mg/kg bw/day (90 day study). The maternal NOAEL was 5 mg/kg/day; the developmental NOAEL was 50 mg/kg/day. The NOAEL from maternal toxicity will be used for the calculation of margin of safety. Irritation / sensitisation Most of the studies are old and not complying with GLP. Presentation of four of the studies is inadequate, among which 1 is unreadable. N,N-bis(2-hydroxyethyl)-p-phenylenediamine sulphate was found to be irritant to mucous membrane.","page":30,"pdf":"sccp_o_065.pdf","row_type":"noael_study","study_id":"sccp_o_065_noael_008"}
ToxValDB_ECHA_IUCLID 7 endpoints
Source Endpoint Type Value Unit Species Route Duration Study Type Reference
ToxValDB_ECHA_IUCLID NOAEL =40 mg/kg bw/day Rat oral - chronic QUALITY=2 (reliable with restrictions); STORED_SOURCE_RECORD=https://clowder.edap-cluster.com/files/669eaa0ce4b0a7c65d1b403c; RECORD_SOURCE_LEVEL=Extraction document; SOURCE_URL=https://echa.europa.eu/; SUBSOURCE_URL=https://echa.europa.eu/registration-dossier/-/registered-dossier/23320/7/8?documentUUID=39800027-eaeb-4fa6-8981-5ae87e9a1f79; YEAR=1979; ORIGINAL_YEAR=1979; STUDY_GROUP=ECHA IUCLID_dup_Carcinogenicity_15818400_15820063:M:--; QC_CATEGORY=Programmatically extracted from structured data source; Source overall passed QC, but this record was not manually checked; QC_STATUS=not determined; SOURCE_HASH=ToxValhc_53d206183a90d753f7251b1cfa99479f
ToxValDB_ECHA_IUCLID NOAEL =48 mg/kg bw/day Rat oral - chronic QUALITY=2 (reliable with restrictions); STORED_SOURCE_RECORD=https://clowder.edap-cluster.com/files/669eaa0ce4b0a7c65d1b403c; RECORD_SOURCE_LEVEL=Extraction document; SOURCE_URL=https://echa.europa.eu/; SUBSOURCE_URL=https://echa.europa.eu/registration-dossier/-/registered-dossier/23320/7/8?documentUUID=39800027-eaeb-4fa6-8981-5ae87e9a1f79; YEAR=1979; ORIGINAL_YEAR=1979; STUDY_GROUP=ECHA IUCLID_dup_Carcinogenicity_15818401_15820082:F:--; QC_CATEGORY=Programmatically extracted from structured data source; Source overall passed QC, but this record was not manually checked; QC_STATUS=not determined; SOURCE_HASH=ToxValhc_e4b864364696c7143a200cd0bf7aed73
ToxValDB_ECHA_IUCLID NOAEL >=121 mg/kg bw/day Rat oral - chronic QUALITY=2 (reliable with restrictions); STORED_SOURCE_RECORD=https://clowder.edap-cluster.com/files/669eaa0ce4b0a7c65d1b403c; RECORD_SOURCE_LEVEL=Extraction document; SOURCE_URL=https://echa.europa.eu/; SUBSOURCE_URL=https://echa.europa.eu/registration-dossier/-/registered-dossier/23320/7/8?documentUUID=39800027-eaeb-4fa6-8981-5ae87e9a1f79; YEAR=1979; ORIGINAL_YEAR=1979; STUDY_GROUP=ECHA IUCLID_dup_Carcinogenicity_15818400_15820063:M:--; QC_CATEGORY=Programmatically extracted from structured data source; Source overall passed QC, and this record was expert reviewed; QC_STATUS=pass; SOURCE_HASH=ToxValhc_27c8ba9fa948ff841831ee2283ed84fe
ToxValDB_ECHA_IUCLID NOAEL >=146 mg/kg bw/day Rat oral - chronic QUALITY=2 (reliable with restrictions); STORED_SOURCE_RECORD=https://clowder.edap-cluster.com/files/669eaa0ce4b0a7c65d1b403c; RECORD_SOURCE_LEVEL=Extraction document; SOURCE_URL=https://echa.europa.eu/; SUBSOURCE_URL=https://echa.europa.eu/registration-dossier/-/registered-dossier/23320/7/8?documentUUID=39800027-eaeb-4fa6-8981-5ae87e9a1f79; YEAR=1979; ORIGINAL_YEAR=1979; STUDY_GROUP=ECHA IUCLID_dup_Carcinogenicity_15818401_15820082:F:--; QC_CATEGORY=Programmatically extracted from structured data source; Source overall passed QC, and this record was expert reviewed; QC_STATUS=pass; SOURCE_HASH=ToxValhc_5520027d49a69541aa84ec524d0993d0
ToxValDB_ECHA_IUCLID NOAEL =5 mg/kg bw/day Rat oral - reproduction developmental QUALITY=1 (reliable without restriction); STORED_SOURCE_RECORD=https://clowder.edap-cluster.com/files/669eac32e4b0a7c65d1bde3a; RECORD_SOURCE_LEVEL=Extraction document; SOURCE_URL=https://echa.europa.eu/; SUBSOURCE_URL=https://echa.europa.eu/registration-dossier/-/registered-dossier/23320/7/9/3?documentUUID=39800027-eaeb-4fa6-8981-5ae87e9a1f79; YEAR=1979; ORIGINAL_YEAR=1979; TOXICOLOGICAL_EFFECT=maternal: body weight and weight gain|maternal: food consumption and compound intake; TOXICOLOGICAL_EFFECT_CATEGORY=body weight|food and/or water consumption; STUDY_GROUP=ECHA IUCLID_dup_Developmental Toxicity Teratogenicity_15822220_15824924:F:-maternal; QC_CATEGORY=Programmatically extracted from structured data source; Source overall passed QC, but this record was not manually checked; QC_STATUS=not determined; SOURCE_HASH=ToxValhc_176c069c5ffd3930dc4e89441a4e3098
ToxValDB_ECHA_IUCLID NOAEL >=50 mg/kg bw/day Rat oral - developmental QUALITY=1 (reliable without restriction); STORED_SOURCE_RECORD=https://clowder.edap-cluster.com/files/669eac32e4b0a7c65d1bde3a; RECORD_SOURCE_LEVEL=Extraction document; SOURCE_URL=https://echa.europa.eu/; SUBSOURCE_URL=https://echa.europa.eu/registration-dossier/-/registered-dossier/23320/7/9/3?documentUUID=39800027-eaeb-4fa6-8981-5ae87e9a1f79; YEAR=1979; ORIGINAL_YEAR=1979; STUDY_GROUP=ECHA IUCLID_dup_Developmental Toxicity Teratogenicity_15821406_15824923:-:-fetal; QC_CATEGORY=Programmatically extracted from structured data source; Source overall passed QC, and this record was expert reviewed; QC_STATUS=pass; SOURCE_HASH=ToxValhc_096edad2fce30ce98e0481985e1f77c9
ToxValDB_ECHA_IUCLID NOAEL =20 mg/kg bw/day Rat oral - reproduction developmental QUALITY=1 (reliable without restriction); STORED_SOURCE_RECORD=https://clowder.edap-cluster.com/files/669eac32e4b0a7c65d1bde42; RECORD_SOURCE_LEVEL=Extraction document; SOURCE_URL=https://echa.europa.eu/; SUBSOURCE_URL=https://echa.europa.eu/registration-dossier/-/registered-dossier/23320/7/9/3?documentUUID=39800027-eaeb-4fa6-8981-5ae87e9a1f79; YEAR=1979; ORIGINAL_YEAR=1979; STUDY_GROUP=ECHA IUCLID_dup_Developmental Toxicity Teratogenicity_15822220_15824924:F:-maternal; QC_CATEGORY=Programmatically extracted from structured data source; Source overall passed QC, and this record was expert reviewed; QC_STATUS=pass; SOURCE_HASH=ToxValhc_30633822a2eb672d35ee3a91a30cf75d
ToxValDB_GESTIS_DNEL 1 endpoint
Source Endpoint Type Value Unit Species Route Duration Study Type Reference
ToxValDB_GESTIS_DNEL DNEL systemic =0.176 mg/m3 Human inhalation - Toxicity Value STORED_SOURCE_RECORD=https://clowder.edap-cluster.com/files/6543dd69e4b045b9ff7cd87e; RECORD_SOURCE_LEVEL=Extraction document; SOURCE_URL=https://www.dguv.de/ifa/gestis/gestis-dnel-liste/index-2.jsp; STUDY_GROUP=GESTIS DNEL:15629796:-:--; QC_CATEGORY=Programmatically extracted from structured data source; Source overall passed QC, but this record was not manually checked; QC_STATUS=not determined; SOURCE_HASH=ToxValhc_077eaa48df163558f36194848948a5e6
UnifiedCodex:SCCS_SHADOW:beta.noael_studies 11 endpoints
Source Endpoint Type Value Unit Species Route Duration Study Type Reference
UnifiedCodex:SCCS_SHADOW:beta.noael_studies - 5 mg/kg bw/day - - - - SOURCE_SUBDIR=sccp_o_065; REPORT_TITLE=Opinion on N,N-bis(2-hydroxyethyl)-p-phenylenediamine sulfate COLIPA N° A50; OPINION_NUMBER=SCCP/0983/06; COMMITTEE=Scientific Committee on Consumer Products (SCCP); REPORT_DATE=20 June 2006; VALUE_TEXT=5; DOSE=ed clinical observations for surviving animals given 100/25 mg/kg/day included thin appearance, mild tremors, few faeces, and rough hair coat for males and females and ocular fasciculation and swaying gait for females only.; EFFECT=ed clinical observations for surviving animals given 100/25 mg/kg/day included thin appearance, mild tremors, few faeces, and rough hair coat for males and females and ocular fasciculation and swaying gait for females only. There were no remarkable clinical observations for control animals or animals given 50/5 mg/kg/day. There was a decrease in mean body weights and an increase in kidney weight in animals in the 100/25 mg/kg group. No adverse effects were observed in the 50/5 mg/kg bw/day group, and therefore the NOAEL in this study was 5 mg/kg bw/day. Ref: 18; CITATION=Ref: 18; CITATION_NUMBERS=[18]; REFERENCE=Ref: 18; DETAILS_JSON={"cas_number":"54381-16-7","citation":"Ref: 18","dose":"ed clinical observations for surviving animals given 100/25 mg/kg/day included thin appearance, mild tremors, few faeces, and rough hair coat for males and females and ocular fasciculation and swaying gait for females only.","duration":"","effect":"ed clinical observations for surviving animals given 100/25 mg/kg/day included thin appearance, mild tremors, few faeces, and rough hair coat for males and females and ocular fasciculation and swaying gait for females only. There were no remarkable clinical observations for control animals or animals given 50/5 mg/kg/day. There was a decrease in mean body weights and an increase in kidney weight in animals in the 100/25 mg/kg group. No adverse effects were observed in the 50/5 mg/kg bw/day group, and therefore the NOAEL in this study was 5 mg/kg bw/day. Ref: 18","endpoint":"","ingredient":"N,N-bis(2-hydroxyethyl)-p-phenylenediamine sulphate (INCI)","loael_value":"","noael_unit":"mg/kg bw/day","noael_value":"5","page":15,"route":"","species":"","study_id":"sccp_o_065_noael_001"}
UnifiedCodex:SCCS_SHADOW:beta.noael_studies carcinogenicity 20 mg/kg bw/day - - 91 days carcinogenicity SOURCE_SUBDIR=sccp_o_065; REPORT_TITLE=Opinion on N,N-bis(2-hydroxyethyl)-p-phenylenediamine sulfate COLIPA N° A50; OPINION_NUMBER=SCCP/0983/06; COMMITTEE=Scientific Committee on Consumer Products (SCCP); REPORT_DATE=20 June 2006; VALUE_TEXT=20; DOSE=Results Up to the highest dose level, no adverse effects were noted after administration of the test substance for 91 days, and therefore the NOAEL in this study was 20 mg/kg bw/day.; EFFECT=inning after Week 10. Blood and urine samples for haematology, coagulation, clinical chemistry, urinalysis, and urine chemistry were collected at each scheduled sacrifice. At each necropsy, macroscopic observations were recorded, selected organs weighed, and selected tissues collected and preserved. Sperm was collected and analysed for motility, morphology and total counts. Results Up to the highest dose level, no adverse effects were noted after administration of the test substance for 91 days, and therefore the NOAEL in this study was 20 mg/kg bw/day. Comment According to OECD 408, the highest dose level should induce toxicity. Ref.: 19 3.3.5.3. Chronic (> 12 months) toxicity See point 3.3.7. Carcinogenicity 3.3.6. Mutagenicity / Genotoxicity 3.3.6.1. Mutagenicity / Genotoxicity in vitro Bacterial gene mutation assay Guideline: OECD 471 (1997) Species/strain: Salmonella typhimurium TA98, TA100, TA1535, and TA1537, Escherichia coli WP2uvrA(pKM101); CITATION=Ref.: 19 3; CITATION_NUMBERS=[19,3]; REFERENCE=Ref.: 19 3; DETAILS_JSON={"cas_number":"54381-16-7","citation":"Ref.: 19 3","dose":"Results Up to the highest dose level, no adverse effects were noted after administration of the test substance for 91 days, and therefore the NOAEL in this study was 20 mg/kg bw/day.","duration":"91 days","effect":"inning after Week 10. Blood and urine samples for haematology, coagulation, clinical chemistry, urinalysis, and urine chemistry were collected at each scheduled sacrifice. At each necropsy, macroscopic observations were recorded, selected organs weighed, and selected tissues collected and preserved. Sperm was collected and analysed for motility, morphology and total counts. Results Up to the highest dose level, no adverse effects were noted after administration of the test substance for 91 days, and therefore the NOAEL in this study was 20 mg/kg bw/day. Comment According to OECD 408, the highest dose level should induce toxicity. Ref.: 19 3.3.5.3. Chronic (> 12 months) toxicity See point 3.3.7. Carcinogenicity 3.3.6. Mutagenicity / Genotoxicity 3.3.6.1. Mutagenicity / Genotoxicity in vitro Bacterial gene mutation assay Guideline: OECD 471 (1997) Species/strain: Salmonella typhimurium TA98, TA100, TA1535, and TA1537, Escherichia coli WP2uvrA(pKM101)","endpoint":"carcinogenicity","ingredient":"N,N-bis(2-hydroxyethyl)-p-phenylenediamine sulphate (INCI)","loael_value":"","noael_unit":"mg/kg bw/day","noael_value":"20","page":16,"route":"","species":"","study_id":"sccp_o_065_noael_002"}
UnifiedCodex:SCCS_SHADOW:beta.noael_studies dermal absorption =0.003 mg/kg rat oral - dermal absorption SOURCE_SUBDIR=sccp_o_065; REPORT_TITLE=Opinion on N,N-bis(2-hydroxyethyl)-p-phenylenediamine sulfate COLIPA N° A50; OPINION_NUMBER=SCCP/0983/06; COMMITTEE=Scientific Committee on Consumer Products (SCCP); REPORT_DATE=20 June 2006; VALUE_TEXT== 0.003; DOSE=Safety evaluation (including calculation of the MoS) CALCULATION OF THE MARGIN OF SAFETY (N,N-Bis(2-hydroxyethyl)-p-phenylenediamine sulfate) (Oxidative/permanent) Maximum absorption through the skin A (μg/cm²) = 0.252 µg/cm² Skin Area surface SAS (cm²) = 700 cm² Dermal absorption per treatment SAS x A x 0.001 = 0.1764 mg Typical body weight of...; EFFECT=d was performed in 1984. Ref.: 16 3.3.12. Special investigations See point 3.3.7. 3.3.13. Safety evaluation (including calculation of the MoS) CALCULATION OF THE MARGIN OF SAFETY (N,N-Bis(2-hydroxyethyl)-p-phenylenediamine sulfate) (Oxidative/permanent) Maximum absorption through the skin A (μg/cm²) = 0.252 µg/cm² Skin Area surface SAS (cm²) = 700 cm² Dermal absorption per treatment SAS x A x 0.001 = 0.1764 mg Typical body weight of human = 60 kg Systemic exposure dose (SED) SAS x A x 0.001/60 = 0.003 mg/kg No observed adverse effect level (mg/kg) NOAEL = 5 mg/kg (rat, oral, maternal toxicity) Margin of Safety NOAEL/SED = 1667 3.3.14. Discussion Physico-chemical specification N,N-bis(2-hydroxyethyl)-p-phenylenediamine is a tertiary amine, and thus, it is prone to nitrosation. The substance should not be used in combination with nitrosating agents. Stability of N,N-Bis(2-hydroxyethyl)-p-phenylenediamine is marketed products is not reported. The physico- chemical characterisation and purity of the substance is not reported in several studies. Ge; CITATION=Ref.: 16 3; CITATION_NUMBERS=[16,3]; REFERENCE=Ref.: 16 3; DETAILS_JSON={"cas_number":"54381-16-7","citation":"Ref.: 16 3","dose":"Safety evaluation (including calculation of the MoS) CALCULATION OF THE MARGIN OF SAFETY (N,N-Bis(2-hydroxyethyl)-p-phenylenediamine sulfate) (Oxidative/permanent) Maximum absorption through the skin A (μg/cm²) = 0.252 µg/cm² Skin Area surface SAS (cm²) = 700 cm² Dermal absorption per treatment SAS x A x 0.001 = 0.1764 mg Typical body weight of...","duration":"","effect":"d was performed in 1984. Ref.: 16 3.3.12. Special investigations See point 3.3.7. 3.3.13. Safety evaluation (including calculation of the MoS) CALCULATION OF THE MARGIN OF SAFETY (N,N-Bis(2-hydroxyethyl)-p-phenylenediamine sulfate) (Oxidative/permanent) Maximum absorption through the skin A (μg/cm²) = 0.252 µg/cm² Skin Area surface SAS (cm²) = 700 cm² Dermal absorption per treatment SAS x A x 0.001 = 0.1764 mg Typical body weight of human = 60 kg Systemic exposure dose (SED) SAS x A x 0.001/60 = 0.003 mg/kg No observed adverse effect level (mg/kg) NOAEL = 5 mg/kg (rat, oral, maternal toxicity) Margin of Safety NOAEL/SED = 1667 3.3.14. Discussion Physico-chemical specification N,N-bis(2-hydroxyethyl)-p-phenylenediamine is a tertiary amine, and thus, it is prone to nitrosation. The substance should not be used in combination with nitrosating agents. Stability of N,N-Bis(2-hydroxyethyl)-p-phenylenediamine is marketed products is not reported. The physico- chemical characterisation and purity of the substance is not reported in several studies. Ge","endpoint":"dermal absorption","ingredient":"N,N-bis(2-hydroxyethyl)-p-phenylenediamine sulphate (INCI)","loael_value":"","noael_unit":"mg/kg","noael_value":"= 0.003","page":30,"route":"oral","species":"rat","study_id":"sccp_o_065_noael_005"}
UnifiedCodex:SCCS_SHADOW:beta.noael_studies dermal absorption =5 mg/kg rat oral - dermal absorption SOURCE_SUBDIR=sccp_o_065; REPORT_TITLE=Opinion on N,N-bis(2-hydroxyethyl)-p-phenylenediamine sulfate COLIPA N° A50; OPINION_NUMBER=SCCP/0983/06; COMMITTEE=Scientific Committee on Consumer Products (SCCP); REPORT_DATE=20 June 2006; VALUE_TEXT== 5; DOSE=Safety evaluation (including calculation of the MoS) CALCULATION OF THE MARGIN OF SAFETY (N,N-Bis(2-hydroxyethyl)-p-phenylenediamine sulfate) (Oxidative/permanent) Maximum absorption through the skin A (μg/cm²) = 0.252 µg/cm² Skin Area surface SAS (cm²) = 700 cm² Dermal absorption per treatment SAS x A x 0.001 = 0.1764 mg Typical body weight of...; EFFECT=. Special investigations See point 3.3.7. 3.3.13. Safety evaluation (including calculation of the MoS) CALCULATION OF THE MARGIN OF SAFETY (N,N-Bis(2-hydroxyethyl)-p-phenylenediamine sulfate) (Oxidative/permanent) Maximum absorption through the skin A (μg/cm²) = 0.252 µg/cm² Skin Area surface SAS (cm²) = 700 cm² Dermal absorption per treatment SAS x A x 0.001 = 0.1764 mg Typical body weight of human = 60 kg Systemic exposure dose (SED) SAS x A x 0.001/60 = 0.003 mg/kg No observed adverse effect level (mg/kg) NOAEL = 5 mg/kg (rat, oral, maternal toxicity) Margin of Safety NOAEL/SED = 1667 3.3.14. Discussion Physico-chemical specification N,N-bis(2-hydroxyethyl)-p-phenylenediamine is a tertiary amine, and thus, it is prone to nitrosation. The substance should not be used in combination with nitrosating agents. Stability of N,N-Bis(2-hydroxyethyl)-p-phenylenediamine is marketed products is not reported. The physico- chemical characterisation and purity of the substance is not reported in several studies. General toxicity; CITATION_NUMBERS=[]; DETAILS_JSON={"cas_number":"54381-16-7","citation":"","dose":"Safety evaluation (including calculation of the MoS) CALCULATION OF THE MARGIN OF SAFETY (N,N-Bis(2-hydroxyethyl)-p-phenylenediamine sulfate) (Oxidative/permanent) Maximum absorption through the skin A (μg/cm²) = 0.252 µg/cm² Skin Area surface SAS (cm²) = 700 cm² Dermal absorption per treatment SAS x A x 0.001 = 0.1764 mg Typical body weight of...","duration":"","effect":". Special investigations See point 3.3.7. 3.3.13. Safety evaluation (including calculation of the MoS) CALCULATION OF THE MARGIN OF SAFETY (N,N-Bis(2-hydroxyethyl)-p-phenylenediamine sulfate) (Oxidative/permanent) Maximum absorption through the skin A (μg/cm²) = 0.252 µg/cm² Skin Area surface SAS (cm²) = 700 cm² Dermal absorption per treatment SAS x A x 0.001 = 0.1764 mg Typical body weight of human = 60 kg Systemic exposure dose (SED) SAS x A x 0.001/60 = 0.003 mg/kg No observed adverse effect level (mg/kg) NOAEL = 5 mg/kg (rat, oral, maternal toxicity) Margin of Safety NOAEL/SED = 1667 3.3.14. Discussion Physico-chemical specification N,N-bis(2-hydroxyethyl)-p-phenylenediamine is a tertiary amine, and thus, it is prone to nitrosation. The substance should not be used in combination with nitrosating agents. Stability of N,N-Bis(2-hydroxyethyl)-p-phenylenediamine is marketed products is not reported. The physico- chemical characterisation and purity of the substance is not reported in several studies. General toxicity","endpoint":"dermal absorption","ingredient":"N,N-bis(2-hydroxyethyl)-p-phenylenediamine sulphate (INCI)","loael_value":"","noael_unit":"mg/kg","noael_value":"= 5","page":30,"route":"oral","species":"rat","study_id":"sccp_o_065_noael_006"}
UnifiedCodex:SCCS_SHADOW:beta.noael_studies dermal absorption =5 mg/kg rat oral - dermal absorption SOURCE_SUBDIR=sccp_o_065; REPORT_TITLE=Opinion on N,N-bis(2-hydroxyethyl)-p-phenylenediamine sulfate COLIPA N° A50; OPINION_NUMBER=SCCP/0983/06; COMMITTEE=Scientific Committee on Consumer Products (SCCP); REPORT_DATE=20 June 2006; VALUE_TEXT== 5; DOSE=ion (including calculation of the MoS) CALCULATION OF THE MARGIN OF SAFETY (N,N-Bis(2-hydroxyethyl)-p-phenylenediamine sulfate) (Oxidative/permanent) Maximum absorption through the skin A (μg/cm²) = 0.252 µg/cm² Skin Area surface SAS (cm²) = 700 cm² Dermal absorption per treatment SAS x A x 0.001 = 0.1764 mg Typical body weight of human = 60 kg...; EFFECT=ion (including calculation of the MoS) CALCULATION OF THE MARGIN OF SAFETY (N,N-Bis(2-hydroxyethyl)-p-phenylenediamine sulfate) (Oxidative/permanent) Maximum absorption through the skin A (μg/cm²) = 0.252 µg/cm² Skin Area surface SAS (cm²) = 700 cm² Dermal absorption per treatment SAS x A x 0.001 = 0.1764 mg Typical body weight of human = 60 kg Systemic exposure dose (SED) SAS x A x 0.001/60 = 0.003 mg/kg No observed adverse effect level (mg/kg) NOAEL = 5 mg/kg (rat, oral, maternal toxicity) Margin of Safety NOAEL/SED = 1667 3.3.14. Discussion Physico-chemical specification N,N-bis(2-hydroxyethyl)-p-phenylenediamine is a tertiary amine, and thus, it is prone to nitrosation. The substance should not be used in combination with nitrosating agents. Stability of N,N-Bis(2-hydroxyethyl)-p-phenylenediamine is marketed products is not reported. The physico- chemical characterisation and purity of the substance is not reported in several studies. General toxicity The oral LD50 in 2 (non-guideline) studies after oral administrat; CITATION_NUMBERS=[]; DETAILS_JSON={"cas_number":"54381-16-7","citation":"","dose":"ion (including calculation of the MoS) CALCULATION OF THE MARGIN OF SAFETY (N,N-Bis(2-hydroxyethyl)-p-phenylenediamine sulfate) (Oxidative/permanent) Maximum absorption through the skin A (μg/cm²) = 0.252 µg/cm² Skin Area surface SAS (cm²) = 700 cm² Dermal absorption per treatment SAS x A x 0.001 = 0.1764 mg Typical body weight of human = 60 kg...","duration":"","effect":"ion (including calculation of the MoS) CALCULATION OF THE MARGIN OF SAFETY (N,N-Bis(2-hydroxyethyl)-p-phenylenediamine sulfate) (Oxidative/permanent) Maximum absorption through the skin A (μg/cm²) = 0.252 µg/cm² Skin Area surface SAS (cm²) = 700 cm² Dermal absorption per treatment SAS x A x 0.001 = 0.1764 mg Typical body weight of human = 60 kg Systemic exposure dose (SED) SAS x A x 0.001/60 = 0.003 mg/kg No observed adverse effect level (mg/kg) NOAEL = 5 mg/kg (rat, oral, maternal toxicity) Margin of Safety NOAEL/SED = 1667 3.3.14. Discussion Physico-chemical specification N,N-bis(2-hydroxyethyl)-p-phenylenediamine is a tertiary amine, and thus, it is prone to nitrosation. The substance should not be used in combination with nitrosating agents. Stability of N,N-Bis(2-hydroxyethyl)-p-phenylenediamine is marketed products is not reported. The physico- chemical characterisation and purity of the substance is not reported in several studies. General toxicity The oral LD50 in 2 (non-guideline) studies after oral administrat","endpoint":"dermal absorption","ingredient":"N,N-bis(2-hydroxyethyl)-p-phenylenediamine sulphate (INCI)","loael_value":"","noael_unit":"mg/kg","noael_value":"= 5","page":30,"route":"oral","species":"rat","study_id":"sccp_o_065_noael_007"}
UnifiedCodex:SCCS_SHADOW:beta.noael_studies developmental toxicity 5 mg/kg/day human oral developmental developmental toxicity SOURCE_SUBDIR=sccp_o_065; REPORT_TITLE=Opinion on N,N-bis(2-hydroxyethyl)-p-phenylenediamine sulfate COLIPA N° A50; OPINION_NUMBER=SCCP/0983/06; COMMITTEE=Scientific Committee on Consumer Products (SCCP); REPORT_DATE=20 June 2006; VALUE_TEXT=5; DOSE=ylenediamine sulfate ____________________________________________________________________________________________ 29 Maternal body weight gains and food consumption were reduced in the 20 and 50 mg/kg/day dosage group during the entire dosage period.; EFFECT=ylenediamine sulfate ____________________________________________________________________________________________ 29 Maternal body weight gains and food consumption were reduced in the 20 and 50 mg/kg/day dosage group during the entire dosage period. Also gravid uterine weights were reduced in these dose groups. Administration of the test substance did not affect litter observations or cause gross external, soft tissue or skeletal foetal alterations. In this study, the maternal no-observable-adverse-effect-level (NOAEL) was 5 mg/kg/day based on reductions on body weight and feed consumption. The developmental NOAEL was 50 mg/kg/day, since no developmental toxicity was observed up to the highest dose tested. Ref.: 28 Remark Dose selection was based on a range finding study, in which at 40 mg/kg (highest dose tested) slight effects on maternal body weight were observed (ref: 27) 3.3.9. Toxicokinetics No data submitted 3.3.10. Photo-induced toxicity No data submitted 3.3.11. Human data Repeated Insult Patch Test Guideline:; CITATION=Ref.: 28 Remark Dose selection was based on a range finding study, in which at 40 mg/kg (highest dose tested) slight effects on maternal body weight were observed (ref: 27) 3; CITATION_NUMBERS=[28,40,27,3]; REFERENCE=Ref.: 28 Remark Dose selection was based on a range finding study, in which at 40 mg/kg (highest dose tested) slight effects on maternal body weight were observed (ref: 27) 3; DETAILS_JSON={"cas_number":"54381-16-7","citation":"Ref.: 28 Remark Dose selection was based on a range finding study, in which at 40 mg/kg (highest dose tested) slight effects on maternal body weight were observed (ref: 27) 3","dose":"ylenediamine sulfate ____________________________________________________________________________________________ 29 Maternal body weight gains and food consumption were reduced in the 20 and 50 mg/kg/day dosage group during the entire dosage period.","duration":"developmental","effect":"ylenediamine sulfate ____________________________________________________________________________________________ 29 Maternal body weight gains and food consumption were reduced in the 20 and 50 mg/kg/day dosage group during the entire dosage period. Also gravid uterine weights were reduced in these dose groups. Administration of the test substance did not affect litter observations or cause gross external, soft tissue or skeletal foetal alterations. In this study, the maternal no-observable-adverse-effect-level (NOAEL) was 5 mg/kg/day based on reductions on body weight and feed consumption. The developmental NOAEL was 50 mg/kg/day, since no developmental toxicity was observed up to the highest dose tested. Ref.: 28 Remark Dose selection was based on a range finding study, in which at 40 mg/kg (highest dose tested) slight effects on maternal body weight were observed (ref: 27) 3.3.9. Toxicokinetics No data submitted 3.3.10. Photo-induced toxicity No data submitted 3.3.11. Human data Repeated Insult Patch Test Guideline:","endpoint":"developmental toxicity","ingredient":"N,N-bis(2-hydroxyethyl)-p-phenylenediamine sulphate (INCI)","loael_value":"","noael_unit":"mg/kg/day","noael_value":"5","page":29,"route":"oral","species":"human","study_id":"sccp_o_065_noael_003"}
UnifiedCodex:SCCS_SHADOW:beta.noael_studies developmental toxicity 50 mg/kg/day human oral developmental developmental toxicity SOURCE_SUBDIR=sccp_o_065; REPORT_TITLE=Opinion on N,N-bis(2-hydroxyethyl)-p-phenylenediamine sulfate COLIPA N° A50; OPINION_NUMBER=SCCP/0983/06; COMMITTEE=Scientific Committee on Consumer Products (SCCP); REPORT_DATE=20 June 2006; VALUE_TEXT=50; DOSE=_______________ 29 Maternal body weight gains and food consumption were reduced in the 20 and 50 mg/kg/day dosage group during the entire dosage period.; EFFECT=_______________ 29 Maternal body weight gains and food consumption were reduced in the 20 and 50 mg/kg/day dosage group during the entire dosage period. Also gravid uterine weights were reduced in these dose groups. Administration of the test substance did not affect litter observations or cause gross external, soft tissue or skeletal foetal alterations. In this study, the maternal no-observable-adverse-effect-level (NOAEL) was 5 mg/kg/day based on reductions on body weight and feed consumption. The developmental NOAEL was 50 mg/kg/day, since no developmental toxicity was observed up to the highest dose tested. Ref.: 28 Remark Dose selection was based on a range finding study, in which at 40 mg/kg (highest dose tested) slight effects on maternal body weight were observed (ref: 27) 3.3.9. Toxicokinetics No data submitted 3.3.10. Photo-induced toxicity No data submitted 3.3.11. Human data Repeated Insult Patch Test Guideline: / Species/strain: human female volunteers Group size: 116 Test substance: N,N-bis(2-hydroxyethyl)-; CITATION=Ref.: 28 Remark Dose selection was based on a range finding study, in which at 40 mg/kg (highest dose tested) slight effects on maternal body weight were observed (ref: 27) 3; CITATION_NUMBERS=[28,40,27,3]; REFERENCE=Ref.: 28 Remark Dose selection was based on a range finding study, in which at 40 mg/kg (highest dose tested) slight effects on maternal body weight were observed (ref: 27) 3; DETAILS_JSON={"cas_number":"54381-16-7","citation":"Ref.: 28 Remark Dose selection was based on a range finding study, in which at 40 mg/kg (highest dose tested) slight effects on maternal body weight were observed (ref: 27) 3","dose":"_______________ 29 Maternal body weight gains and food consumption were reduced in the 20 and 50 mg/kg/day dosage group during the entire dosage period.","duration":"developmental","effect":"_______________ 29 Maternal body weight gains and food consumption were reduced in the 20 and 50 mg/kg/day dosage group during the entire dosage period. Also gravid uterine weights were reduced in these dose groups. Administration of the test substance did not affect litter observations or cause gross external, soft tissue or skeletal foetal alterations. In this study, the maternal no-observable-adverse-effect-level (NOAEL) was 5 mg/kg/day based on reductions on body weight and feed consumption. The developmental NOAEL was 50 mg/kg/day, since no developmental toxicity was observed up to the highest dose tested. Ref.: 28 Remark Dose selection was based on a range finding study, in which at 40 mg/kg (highest dose tested) slight effects on maternal body weight were observed (ref: 27) 3.3.9. Toxicokinetics No data submitted 3.3.10. Photo-induced toxicity No data submitted 3.3.11. Human data Repeated Insult Patch Test Guideline: / Species/strain: human female volunteers Group size: 116 Test substance: N,N-bis(2-hydroxyethyl)-","endpoint":"developmental toxicity","ingredient":"N,N-bis(2-hydroxyethyl)-p-phenylenediamine sulphate (INCI)","loael_value":"","noael_unit":"mg/kg/day","noael_value":"50","page":29,"route":"oral","species":"human","study_id":"sccp_o_065_noael_004"}
UnifiedCodex:SCCS_SHADOW:beta.noael_studies developmental toxicity 31 mg/kg bw - oral 14 day developmental toxicity SOURCE_SUBDIR=sccp_o_065; REPORT_TITLE=Opinion on N,N-bis(2-hydroxyethyl)-p-phenylenediamine sulfate COLIPA N° A50; OPINION_NUMBER=SCCP/0983/06; COMMITTEE=Scientific Committee on Consumer Products (SCCP); REPORT_DATE=20 June 2006; VALUE_TEXT=31; DOSE=General toxicity The oral LD50 in 2 (non-guideline) studies after oral administration ranged between 100 and 400 mg/kg bw.; EFFECT=tertiary amine, and thus, it is prone to nitrosation. The substance should not be used in combination with nitrosating agents. Stability of N,N-Bis(2-hydroxyethyl)-p-phenylenediamine is marketed products is not reported. The physico- chemical characterisation and purity of the substance is not reported in several studies. General toxicity The oral LD50 in 2 (non-guideline) studies after oral administration ranged between 100 and 400 mg/kg bw. After i.p. administration the LD50 was between 16 and 31 mg/kg bw. The NOAEL was set at 5 mg/kg bw/day (14 day range-finding study) and at 20 mg/kg bw/day (90 day study). The maternal NOAEL was 5 mg/kg/day; the developmental NOAEL was 50 mg/kg/day. The NOAEL from maternal toxicity will be used for the calculation of margin of safety. Irritation / sensitisation Most of the studies are old and not complying with GLP. Presentation of four of the studies is inadequate, among which 1 is unreadable. N,N-bis(2-hydroxyethyl)-p-phenylenediamine sulphate was found to be irritant to mucous membrane.; CITATION_NUMBERS=[]; DETAILS_JSON={"cas_number":"54381-16-7","citation":"","dose":"General toxicity The oral LD50 in 2 (non-guideline) studies after oral administration ranged between 100 and 400 mg/kg bw.","duration":"14 day","effect":"tertiary amine, and thus, it is prone to nitrosation. The substance should not be used in combination with nitrosating agents. Stability of N,N-Bis(2-hydroxyethyl)-p-phenylenediamine is marketed products is not reported. The physico- chemical characterisation and purity of the substance is not reported in several studies. General toxicity The oral LD50 in 2 (non-guideline) studies after oral administration ranged between 100 and 400 mg/kg bw. After i.p. administration the LD50 was between 16 and 31 mg/kg bw. The NOAEL was set at 5 mg/kg bw/day (14 day range-finding study) and at 20 mg/kg bw/day (90 day study). The maternal NOAEL was 5 mg/kg/day; the developmental NOAEL was 50 mg/kg/day. The NOAEL from maternal toxicity will be used for the calculation of margin of safety. Irritation / sensitisation Most of the studies are old and not complying with GLP. Presentation of four of the studies is inadequate, among which 1 is unreadable. N,N-bis(2-hydroxyethyl)-p-phenylenediamine sulphate was found to be irritant to mucous membrane.","endpoint":"developmental toxicity","ingredient":"N,N-bis(2-hydroxyethyl)-p-phenylenediamine sulphate (INCI)","loael_value":"","noael_unit":"mg/kg bw","noael_value":"31","page":30,"route":"oral","species":"","study_id":"sccp_o_065_noael_008"}
UnifiedCodex:SCCS_SHADOW:beta.noael_studies developmental toxicity 5 mg/kg/day human oral 14 day developmental toxicity SOURCE_SUBDIR=sccp_o_065; REPORT_TITLE=Opinion on N,N-bis(2-hydroxyethyl)-p-phenylenediamine sulfate COLIPA N° A50; OPINION_NUMBER=SCCP/0983/06; COMMITTEE=Scientific Committee on Consumer Products (SCCP); REPORT_DATE=20 June 2006; VALUE_TEXT=5; DOSE=General toxicity The oral LD50 in 2 (non-guideline) studies after oral administration ranged between 100 and 400 mg/kg bw.; EFFECT=sating agents. Stability of N,N-Bis(2-hydroxyethyl)-p-phenylenediamine is marketed products is not reported. The physico- chemical characterisation and purity of the substance is not reported in several studies. General toxicity The oral LD50 in 2 (non-guideline) studies after oral administration ranged between 100 and 400 mg/kg bw. After i.p. administration the LD50 was between 16 and 31 mg/kg bw. The NOAEL was set at 5 mg/kg bw/day (14 day range-finding study) and at 20 mg/kg bw/day (90 day study). The maternal NOAEL was 5 mg/kg/day; the developmental NOAEL was 50 mg/kg/day. The NOAEL from maternal toxicity will be used for the calculation of margin of safety. Irritation / sensitisation Most of the studies are old and not complying with GLP. Presentation of four of the studies is inadequate, among which 1 is unreadable. N,N-bis(2-hydroxyethyl)-p-phenylenediamine sulphate was found to be irritant to mucous membrane. It induced skin sensitisation as shown by LLNA. The substance is a known skin sensitiser in humans.; CITATION_NUMBERS=[]; DETAILS_JSON={"cas_number":"54381-16-7","citation":"","dose":"General toxicity The oral LD50 in 2 (non-guideline) studies after oral administration ranged between 100 and 400 mg/kg bw.","duration":"14 day","effect":"sating agents. Stability of N,N-Bis(2-hydroxyethyl)-p-phenylenediamine is marketed products is not reported. The physico- chemical characterisation and purity of the substance is not reported in several studies. General toxicity The oral LD50 in 2 (non-guideline) studies after oral administration ranged between 100 and 400 mg/kg bw. After i.p. administration the LD50 was between 16 and 31 mg/kg bw. The NOAEL was set at 5 mg/kg bw/day (14 day range-finding study) and at 20 mg/kg bw/day (90 day study). The maternal NOAEL was 5 mg/kg/day; the developmental NOAEL was 50 mg/kg/day. The NOAEL from maternal toxicity will be used for the calculation of margin of safety. Irritation / sensitisation Most of the studies are old and not complying with GLP. Presentation of four of the studies is inadequate, among which 1 is unreadable. N,N-bis(2-hydroxyethyl)-p-phenylenediamine sulphate was found to be irritant to mucous membrane. It induced skin sensitisation as shown by LLNA. The substance is a known skin sensitiser in humans.","endpoint":"developmental toxicity","ingredient":"N,N-bis(2-hydroxyethyl)-p-phenylenediamine sulphate (INCI)","loael_value":"","noael_unit":"mg/kg/day","noael_value":"5","page":30,"route":"oral","species":"human","study_id":"sccp_o_065_noael_009"}
UnifiedCodex:SCCS_SHADOW:beta.noael_studies developmental toxicity 50 mg/kg/day human oral 14 day developmental toxicity SOURCE_SUBDIR=sccp_o_065; REPORT_TITLE=Opinion on N,N-bis(2-hydroxyethyl)-p-phenylenediamine sulfate COLIPA N° A50; OPINION_NUMBER=SCCP/0983/06; COMMITTEE=Scientific Committee on Consumer Products (SCCP); REPORT_DATE=20 June 2006; VALUE_TEXT=50; DOSE=General toxicity The oral LD50 in 2 (non-guideline) studies after oral administration ranged between 100 and 400 mg/kg bw.; EFFECT=roxyethyl)-p-phenylenediamine is marketed products is not reported. The physico- chemical characterisation and purity of the substance is not reported in several studies. General toxicity The oral LD50 in 2 (non-guideline) studies after oral administration ranged between 100 and 400 mg/kg bw. After i.p. administration the LD50 was between 16 and 31 mg/kg bw. The NOAEL was set at 5 mg/kg bw/day (14 day range-finding study) and at 20 mg/kg bw/day (90 day study). The maternal NOAEL was 5 mg/kg/day; the developmental NOAEL was 50 mg/kg/day. The NOAEL from maternal toxicity will be used for the calculation of margin of safety. Irritation / sensitisation Most of the studies are old and not complying with GLP. Presentation of four of the studies is inadequate, among which 1 is unreadable. N,N-bis(2-hydroxyethyl)-p-phenylenediamine sulphate was found to be irritant to mucous membrane. It induced skin sensitisation as shown by LLNA. The substance is a known skin sensitiser in humans.; CITATION_NUMBERS=[]; DETAILS_JSON={"cas_number":"54381-16-7","citation":"","dose":"General toxicity The oral LD50 in 2 (non-guideline) studies after oral administration ranged between 100 and 400 mg/kg bw.","duration":"14 day","effect":"roxyethyl)-p-phenylenediamine is marketed products is not reported. The physico- chemical characterisation and purity of the substance is not reported in several studies. General toxicity The oral LD50 in 2 (non-guideline) studies after oral administration ranged between 100 and 400 mg/kg bw. After i.p. administration the LD50 was between 16 and 31 mg/kg bw. The NOAEL was set at 5 mg/kg bw/day (14 day range-finding study) and at 20 mg/kg bw/day (90 day study). The maternal NOAEL was 5 mg/kg/day; the developmental NOAEL was 50 mg/kg/day. The NOAEL from maternal toxicity will be used for the calculation of margin of safety. Irritation / sensitisation Most of the studies are old and not complying with GLP. Presentation of four of the studies is inadequate, among which 1 is unreadable. N,N-bis(2-hydroxyethyl)-p-phenylenediamine sulphate was found to be irritant to mucous membrane. It induced skin sensitisation as shown by LLNA. The substance is a known skin sensitiser in humans.","endpoint":"developmental toxicity","ingredient":"N,N-bis(2-hydroxyethyl)-p-phenylenediamine sulphate (INCI)","loael_value":"","noael_unit":"mg/kg/day","noael_value":"50","page":30,"route":"oral","species":"human","study_id":"sccp_o_065_noael_010"}
UnifiedCodex:SCCS_SHADOW:beta.noael_studies developmental toxicity 50 mg/kg/day human oral 14 day developmental toxicity SOURCE_SUBDIR=sccp_o_065; REPORT_TITLE=Opinion on N,N-bis(2-hydroxyethyl)-p-phenylenediamine sulfate COLIPA N° A50; OPINION_NUMBER=SCCP/0983/06; COMMITTEE=Scientific Committee on Consumer Products (SCCP); REPORT_DATE=20 June 2006; VALUE_TEXT=50; DOSE=General toxicity The oral LD50 in 2 (non-guideline) studies after oral administration ranged between 100 and 400 mg/kg bw.; EFFECT=e is marketed products is not reported. The physico- chemical characterisation and purity of the substance is not reported in several studies. General toxicity The oral LD50 in 2 (non-guideline) studies after oral administration ranged between 100 and 400 mg/kg bw. After i.p. administration the LD50 was between 16 and 31 mg/kg bw. The NOAEL was set at 5 mg/kg bw/day (14 day range-finding study) and at 20 mg/kg bw/day (90 day study). The maternal NOAEL was 5 mg/kg/day; the developmental NOAEL was 50 mg/kg/day. The NOAEL from maternal toxicity will be used for the calculation of margin of safety. Irritation / sensitisation Most of the studies are old and not complying with GLP. Presentation of four of the studies is inadequate, among which 1 is unreadable. N,N-bis(2-hydroxyethyl)-p-phenylenediamine sulphate was found to be irritant to mucous membrane. It induced skin sensitisation as shown by LLNA. The substance is a known skin sensitiser in humans.; CITATION_NUMBERS=[]; DETAILS_JSON={"cas_number":"54381-16-7","citation":"","dose":"General toxicity The oral LD50 in 2 (non-guideline) studies after oral administration ranged between 100 and 400 mg/kg bw.","duration":"14 day","effect":"e is marketed products is not reported. The physico- chemical characterisation and purity of the substance is not reported in several studies. General toxicity The oral LD50 in 2 (non-guideline) studies after oral administration ranged between 100 and 400 mg/kg bw. After i.p. administration the LD50 was between 16 and 31 mg/kg bw. The NOAEL was set at 5 mg/kg bw/day (14 day range-finding study) and at 20 mg/kg bw/day (90 day study). The maternal NOAEL was 5 mg/kg/day; the developmental NOAEL was 50 mg/kg/day. The NOAEL from maternal toxicity will be used for the calculation of margin of safety. Irritation / sensitisation Most of the studies are old and not complying with GLP. Presentation of four of the studies is inadequate, among which 1 is unreadable. N,N-bis(2-hydroxyethyl)-p-phenylenediamine sulphate was found to be irritant to mucous membrane. It induced skin sensitisation as shown by LLNA. The substance is a known skin sensitiser in humans.","endpoint":"developmental toxicity","ingredient":"N,N-bis(2-hydroxyethyl)-p-phenylenediamine sulphate (INCI)","loael_value":"","noael_unit":"mg/kg/day","noael_value":"50","page":30,"route":"oral","species":"human","study_id":"sccp_o_065_noael_011"}
openFDA substances 4 endpoints
Source Endpoint Type Value Unit Species Route Duration Study Type Reference
openFDA substances FDA UNII substance identifier 3X5A8DP6HC UNII - - - chemical {"approval_status":null,"molecular_formula":"C10H16N2O2.H2O4S","source_table":"substance_identifiers_fda","substance_class":"chemical","unii_code":"3X5A8DP6HC"}
openFDA substances FDA UNII substance identifier 3X5A8DP6HC UNII - - - chemical {"approval_status":null,"molecular_formula":"C10H16N2O2.H2O4S","source_table":"substance_identifiers_fda","substance_class":"chemical","unii_code":"3X5A8DP6HC"}
openFDA substances FDA UNII substance identifier 3X5A8DP6HC UNII - - - chemical {"approval_status":null,"molecular_formula":"C10H16N2O2.H2O4S","source_table":"substance_identifiers_fda","substance_class":"chemical","unii_code":"3X5A8DP6HC"}
openFDA substances FDA UNII substance identifier 3X5A8DP6HC UNII - - - chemical {"approval_status":null,"molecular_formula":"C10H16N2O2.H2O4S","source_table":"substance_identifiers_fda","substance_class":"chemical","unii_code":"3X5A8DP6HC"}