3-Methylamino-4-nitrophenoxyethanol, TOLUENE-2,5-DIAMINE

SOURCE_SUBDIR=sccp_o_110; REPORT_TITLE=OPINION ON 3-Methylamino-4-nitrophenoxyethanol COLIPA n° B58; OPINION_NUMBER=SCCP/1089/07; COMMITTEE=Scientific Committee on Consumer Products (SCCP); REPORT_DATE=2 October 2007; VALUE_TEXT=100; DOSE=SCCP/1089/07 Opinion on 3-methylamino-4-nitrophenoxyethanol increase in cholesterol levels in both sexes at 1000 mg/kg/day was considered toxicologically significant.; EFFECT=SCCP/1089/07 Opinion on 3-methylamino-4-nitrophenoxyethanol increase in cholesterol levels in both sexes at 1000 mg/kg/day was considered toxicologically significant. Compound-related increases in liver weights were observed in both sexes at 1000 mg/kg/day. Slight to moderate diffuse or centrilobular hepatocellular hypertrophy was observed in 2/10 males at 100 mg/kg/day and in all males and 6/10 females at 1000 mg/kg/day; this was attributed to possible enzyme induction. The NOAEL for the study was 100 mg/kg/day. In the 13 week study, animals were observed once daily for clinical signs and twice daily for mortality/morbidity. Body weight and food consumption were recorded weekly; efficiency of food utilization was calculated weekly using these values. Water consumption was recorded for 7 days during week 10 for control and 400 mg/kg/day dose group males and for 4 days in week 13 for all animals of the control and 400 mg/kg/day dose groups. Ophthalmologic evaluations on control and high-dos; CITATION_NUMBERS=[]; DETAILS_JSON={"cas_number":"59820-63-2","citation":"","dose":"SCCP/1089/07 Opinion on 3-methylamino-4-nitrophenoxyethanol increase in cholesterol levels in both sexes at 1000 mg/kg/day was considered toxicologically significant.","duration":"13 week","effect":"SCCP/1089/07 Opinion on 3-methylamino-4-nitrophenoxyethanol increase in cholesterol levels in both sexes at 1000 mg/kg/day was considered toxicologically significant. Compound-related increases in liver weights were observed in both sexes at 1000 mg/kg/day. Slight to moderate diffuse or centrilobular hepatocellular hypertrophy was observed in 2/10 males at 100 mg/kg/day and in all males and 6/10 females at 1000 mg/kg/day; this was attributed to possible enzyme induction. The NOAEL for the study was 100 mg/kg/day. In the 13 week study, animals were observed once daily for clinical signs and twice daily for mortality/morbidity. Body weight and food consumption were recorded weekly; efficiency of food utilization was calculated weekly using these values. Water consumption was recorded for 7 days during week 10 for control and 400 mg/kg/day dose group males and for 4 days in week 13 for all animals of the control and 400 mg/kg/day dose groups. Ophthalmologic evaluations on control and high-dos","endpoint":"","ingredient":"3-Methylamino-4-nitrophenoxyethanol","loael_value":"","noael_unit":"mg/kg/day","noael_value":"100","page":14,"route":"","species":"","study_id":"sccp_o_110_noael_002"}

sccp_o_110.pdf

SOURCE_SUBDIR=sccp_o_110; REPORT_TITLE=OPINION ON 3-Methylamino-4-nitrophenoxyethanol COLIPA n° B58; OPINION_NUMBER=SCCP/1089/07; COMMITTEE=Scientific Committee on Consumer Products (SCCP); REPORT_DATE=2 October 2007; VALUE_TEXT== 0.002; DOSE=Safety evaluation (including calculation of the MoS) CALCULATION OF THE MARGIN OF SAFETY (3-methylamino-4-nitrophenoxy-ethanol) (Non-oxidative / semi-permanent) Maximum absorption through the skin A (μg/cm2) = 0.19 µg/cm² Skin Area surface SAS (cm2) = 700 cm2 Dermal absorption per treatment SAS x A x 0.001 = 0.133 mg Typical body weight of human...; EFFECT=.11. Human data No data submitted 3.3.12. Special investigations No data submitted 3.3.13. Safety evaluation (including calculation of the MoS) CALCULATION OF THE MARGIN OF SAFETY (3-methylamino-4-nitrophenoxy-ethanol) (Non-oxidative / semi-permanent) Maximum absorption through the skin A (μg/cm2) = 0.19 µg/cm² Skin Area surface SAS (cm2) = 700 cm2 Dermal absorption per treatment SAS x A x 0.001 = 0.133 mg Typical body weight of human = 60 kg Systemic exposure dose (SED) SAS x A x 0.001/60 = 0.002 mg/kg bw No observed adverse effect level NOAEL = 25 mg/kg bw (90day, rat, oral) Margin of Safety NOAEL / SED = 11280 19; CITATION_NUMBERS=[]; DETAILS_JSON={"cas_number":"59820-63-2","citation":"","dose":"Safety evaluation (including calculation of the MoS) CALCULATION OF THE MARGIN OF SAFETY (3-methylamino-4-nitrophenoxy-ethanol) (Non-oxidative / semi-permanent) Maximum absorption through the skin A (μg/cm2) = 0.19 µg/cm² Skin Area surface SAS (cm2) = 700 cm2 Dermal absorption per treatment SAS x A x 0.001 = 0.133 mg Typical body weight of human...","duration":"90day","effect":".11. Human data No data submitted 3.3.12. Special investigations No data submitted 3.3.13. Safety evaluation (including calculation of the MoS) CALCULATION OF THE MARGIN OF SAFETY (3-methylamino-4-nitrophenoxy-ethanol) (Non-oxidative / semi-permanent) Maximum absorption through the skin A (μg/cm2) = 0.19 µg/cm² Skin Area surface SAS (cm2) = 700 cm2 Dermal absorption per treatment SAS x A x 0.001 = 0.133 mg Typical body weight of human = 60 kg Systemic exposure dose (SED) SAS x A x 0.001/60 = 0.002 mg/kg bw No observed adverse effect level NOAEL = 25 mg/kg bw (90day, rat, oral) Margin of Safety NOAEL / SED = 11280 19","endpoint":"dermal absorption","ingredient":"3-Methylamino-4-nitrophenoxyethanol","loael_value":"","noael_unit":"mg/kg bw","noael_value":"= 0.002","page":19,"route":"oral","species":"rat","study_id":"sccp_o_110_noael_008"}

sccp_o_110.pdf

SOURCE_SUBDIR=sccp_o_110; REPORT_TITLE=OPINION ON 3-Methylamino-4-nitrophenoxyethanol COLIPA n° B58; OPINION_NUMBER=SCCP/1089/07; COMMITTEE=Scientific Committee on Consumer Products (SCCP); REPORT_DATE=2 October 2007; VALUE_TEXT== 25; DOSE=Safety evaluation (including calculation of the MoS) CALCULATION OF THE MARGIN OF SAFETY (3-methylamino-4-nitrophenoxy-ethanol) (Non-oxidative / semi-permanent) Maximum absorption through the skin A (μg/cm2) = 0.19 µg/cm² Skin Area surface SAS (cm2) = 700 cm2 Dermal absorption per treatment SAS x A x 0.001 = 0.133 mg Typical body weight of human...; EFFECT=d 3.3.12. Special investigations No data submitted 3.3.13. Safety evaluation (including calculation of the MoS) CALCULATION OF THE MARGIN OF SAFETY (3-methylamino-4-nitrophenoxy-ethanol) (Non-oxidative / semi-permanent) Maximum absorption through the skin A (μg/cm2) = 0.19 µg/cm² Skin Area surface SAS (cm2) = 700 cm2 Dermal absorption per treatment SAS x A x 0.001 = 0.133 mg Typical body weight of human = 60 kg Systemic exposure dose (SED) SAS x A x 0.001/60 = 0.002 mg/kg bw No observed adverse effect level NOAEL = 25 mg/kg bw (90day, rat, oral) Margin of Safety NOAEL / SED = 11280 19; CITATION_NUMBERS=[]; DETAILS_JSON={"cas_number":"59820-63-2","citation":"","dose":"Safety evaluation (including calculation of the MoS) CALCULATION OF THE MARGIN OF SAFETY (3-methylamino-4-nitrophenoxy-ethanol) (Non-oxidative / semi-permanent) Maximum absorption through the skin A (μg/cm2) = 0.19 µg/cm² Skin Area surface SAS (cm2) = 700 cm2 Dermal absorption per treatment SAS x A x 0.001 = 0.133 mg Typical body weight of human...","duration":"90day","effect":"d 3.3.12. Special investigations No data submitted 3.3.13. Safety evaluation (including calculation of the MoS) CALCULATION OF THE MARGIN OF SAFETY (3-methylamino-4-nitrophenoxy-ethanol) (Non-oxidative / semi-permanent) Maximum absorption through the skin A (μg/cm2) = 0.19 µg/cm² Skin Area surface SAS (cm2) = 700 cm2 Dermal absorption per treatment SAS x A x 0.001 = 0.133 mg Typical body weight of human = 60 kg Systemic exposure dose (SED) SAS x A x 0.001/60 = 0.002 mg/kg bw No observed adverse effect level NOAEL = 25 mg/kg bw (90day, rat, oral) Margin of Safety NOAEL / SED = 11280 19","endpoint":"dermal absorption","ingredient":"3-Methylamino-4-nitrophenoxyethanol","loael_value":"","noael_unit":"mg/kg bw","noael_value":"= 25","page":19,"route":"oral","species":"rat","study_id":"sccp_o_110_noael_009"}

sccp_o_110.pdf

SOURCE_SUBDIR=sccp_o_110; REPORT_TITLE=OPINION ON 3-Methylamino-4-nitrophenoxyethanol COLIPA n° B58; OPINION_NUMBER=SCCP/1089/07; COMMITTEE=Scientific Committee on Consumer Products (SCCP); REPORT_DATE=2 October 2007; VALUE_TEXT== 25; DOSE=Safety evaluation (including calculation of the MoS) CALCULATION OF THE MARGIN OF SAFETY (3-methylamino-4-nitrophenoxy-ethanol) (Non-oxidative / semi-permanent) Maximum absorption through the skin A (μg/cm2) = 0.19 µg/cm² Skin Area surface SAS (cm2) = 700 cm2 Dermal absorption per treatment SAS x A x 0.001 = 0.133 mg Typical body weight of human...; EFFECT=13. Safety evaluation (including calculation of the MoS) CALCULATION OF THE MARGIN OF SAFETY (3-methylamino-4-nitrophenoxy-ethanol) (Non-oxidative / semi-permanent) Maximum absorption through the skin A (μg/cm2) = 0.19 µg/cm² Skin Area surface SAS (cm2) = 700 cm2 Dermal absorption per treatment SAS x A x 0.001 = 0.133 mg Typical body weight of human = 60 kg Systemic exposure dose (SED) SAS x A x 0.001/60 = 0.002 mg/kg bw No observed adverse effect level NOAEL = 25 mg/kg bw (90day, rat, oral) Margin of Safety NOAEL / SED = 11280 19; CITATION_NUMBERS=[]; DETAILS_JSON={"cas_number":"59820-63-2","citation":"","dose":"Safety evaluation (including calculation of the MoS) CALCULATION OF THE MARGIN OF SAFETY (3-methylamino-4-nitrophenoxy-ethanol) (Non-oxidative / semi-permanent) Maximum absorption through the skin A (μg/cm2) = 0.19 µg/cm² Skin Area surface SAS (cm2) = 700 cm2 Dermal absorption per treatment SAS x A x 0.001 = 0.133 mg Typical body weight of human...","duration":"90day","effect":"13. Safety evaluation (including calculation of the MoS) CALCULATION OF THE MARGIN OF SAFETY (3-methylamino-4-nitrophenoxy-ethanol) (Non-oxidative / semi-permanent) Maximum absorption through the skin A (μg/cm2) = 0.19 µg/cm² Skin Area surface SAS (cm2) = 700 cm2 Dermal absorption per treatment SAS x A x 0.001 = 0.133 mg Typical body weight of human = 60 kg Systemic exposure dose (SED) SAS x A x 0.001/60 = 0.002 mg/kg bw No observed adverse effect level NOAEL = 25 mg/kg bw (90day, rat, oral) Margin of Safety NOAEL / SED = 11280 19","endpoint":"dermal absorption","ingredient":"3-Methylamino-4-nitrophenoxyethanol","loael_value":"","noael_unit":"mg/kg bw","noael_value":"= 25","page":19,"route":"oral","species":"rat","study_id":"sccp_o_110_noael_010"}

sccp_o_110.pdf

SOURCE_SUBDIR=sccp_o_110; REPORT_TITLE=OPINION ON 3-Methylamino-4-nitrophenoxyethanol COLIPA n° B58; OPINION_NUMBER=SCCP/1089/07; COMMITTEE=Scientific Committee on Consumer Products (SCCP); REPORT_DATE=2 October 2007; VALUE_TEXT=100; DOSE=g on 20 May 1998 the opinion (XXIV/1290/97) with the opinion: “1-(2-hydroxyethyloxy)-3-methylamino-4-nitrobenzene has an acute oral toxicity of 3046 mg/kg bw in the rat.; EFFECT=g on 20 May 1998 the opinion (XXIV/1290/97) with the opinion: “1-(2-hydroxyethyloxy)-3-methylamino-4-nitrobenzene has an acute oral toxicity of 3046 mg/kg bw in the rat. The substance can be classified as irritating to mucous membranes, not irritating to the skin and as a non sensitizer. Percutaneous absorption of a formulation was 0.71% in the presence of hair and 1.13% in the absence of hair for a concentration of the test formulation of 0.15%. In the 28 day study with rats 100 mg/kg/day is considered to be the NOAEL. In the teratogenicity study, no signs of maternal or foetal toxicity were observed after administration of 100 mg/kg bw.” The substance is currently regulated by the Cosmetics Directive (76/768/EC), Annex III, Part 2 under entry 28 on the List of substances provisionally allowed, which cosmetic products must not contain except subject to restrictions and conditions laid down. Submission II for 3-methylamino-4-nitrophenoxyethanol was submitted by COLIPA in July 2005. According to this submission 3-methylamino-4-; CITATION_NUMBERS=[]; DETAILS_JSON={"cas_number":"59820-63-2","citation":"","dose":"g on 20 May 1998 the opinion (XXIV/1290/97) with the opinion: “1-(2-hydroxyethyloxy)-3-methylamino-4-nitrobenzene has an acute oral toxicity of 3046 mg/kg bw in the rat.","duration":"28 day","effect":"g on 20 May 1998 the opinion (XXIV/1290/97) with the opinion: “1-(2-hydroxyethyloxy)-3-methylamino-4-nitrobenzene has an acute oral toxicity of 3046 mg/kg bw in the rat. The substance can be classified as irritating to mucous membranes, not irritating to the skin and as a non sensitizer. Percutaneous absorption of a formulation was 0.71% in the presence of hair and 1.13% in the absence of hair for a concentration of the test formulation of 0.15%. In the 28 day study with rats 100 mg/kg/day is considered to be the NOAEL. In the teratogenicity study, no signs of maternal or foetal toxicity were observed after administration of 100 mg/kg bw.” The substance is currently regulated by the Cosmetics Directive (76/768/EC), Annex III, Part 2 under entry 28 on the List of substances provisionally allowed, which cosmetic products must not contain except subject to restrictions and conditions laid down. Submission II for 3-methylamino-4-nitrophenoxyethanol was submitted by COLIPA in July 2005. According to this submission 3-methylamino-4-","endpoint":"dermal absorption","ingredient":"3-Methylamino-4-nitrophenoxyethanol","loael_value":"","noael_unit":"mg/kg/day","noael_value":"100","page":5,"route":"oral","species":"rat","study_id":"sccp_o_110_noael_001"}

sccp_o_110.pdf

SOURCE_SUBDIR=sccp_o_110; REPORT_TITLE=OPINION ON 3-Methylamino-4-nitrophenoxyethanol COLIPA n° B58; OPINION_NUMBER=SCCP/1089/07; COMMITTEE=Scientific Committee on Consumer Products (SCCP); REPORT_DATE=2 October 2007; VALUE_TEXT=25; DOSE=Data on nitrosamine content is not provided General toxicity Based on lymphoid depletion in the thymus at 100 and 400 mg/kg bw in males, the NOAEL is set at 25 mg/kg bw per day (90-day study in rats).; EFFECT=use of 3-methylamino-4-nitrophenoxy-ethanol in non- oxidative hair dye formulations only. Physico-chemical properties The stability of the test substance in marketed products is not reported. The test substance is a secondary amine and thus is prone to nitrosation. It should not be used in combination with nitrosating substances. The nitrosamine content should be < 50 ppb. Data on nitrosamine content is not provided General toxicity Based on lymphoid depletion in the thymus at 100 and 400 mg/kg bw in males, the NOAEL is set at 25 mg/kg bw per day (90-day study in rats). The NOAEL for maternal toxicity was considered as 100 mg/kg/day and the NOAEL for developmental toxicity was 750 mg/kg/day in the present study. Irritation / sensitisation Under the conditions of the experiments, 3-methylamino-4-nitrophenoxy-ethanol was not irritant to rabbit skin. It showed minimal irritancy to rabbit eyes. 3-Methylamino-4- nitrophenoxy-ethanol was not shown to be a skin sensitizer in a LLNA study. Dermal absorption The number of replicate; CITATION_NUMBERS=[]; DETAILS_JSON={"cas_number":"59820-63-2","citation":"","dose":"Data on nitrosamine content is not provided General toxicity Based on lymphoid depletion in the thymus at 100 and 400 mg/kg bw in males, the NOAEL is set at 25 mg/kg bw per day (90-day study in rats).","duration":"90-day","effect":"use of 3-methylamino-4-nitrophenoxy-ethanol in non- oxidative hair dye formulations only. Physico-chemical properties The stability of the test substance in marketed products is not reported. The test substance is a secondary amine and thus is prone to nitrosation. It should not be used in combination with nitrosating substances. The nitrosamine content should be < 50 ppb. Data on nitrosamine content is not provided General toxicity Based on lymphoid depletion in the thymus at 100 and 400 mg/kg bw in males, the NOAEL is set at 25 mg/kg bw per day (90-day study in rats). The NOAEL for maternal toxicity was considered as 100 mg/kg/day and the NOAEL for developmental toxicity was 750 mg/kg/day in the present study. Irritation / sensitisation Under the conditions of the experiments, 3-methylamino-4-nitrophenoxy-ethanol was not irritant to rabbit skin. It showed minimal irritancy to rabbit eyes. 3-Methylamino-4- nitrophenoxy-ethanol was not shown to be a skin sensitizer in a LLNA study. Dermal absorption The number of replicate","endpoint":"developmental toxicity","ingredient":"3-Methylamino-4-nitrophenoxyethanol","loael_value":"","noael_unit":"mg/kg bw","noael_value":"25","page":20,"route":"dermal","species":"rat","study_id":"sccp_o_110_noael_011"}

sccp_o_110.pdf

SOURCE_SUBDIR=sccp_o_110; REPORT_TITLE=OPINION ON 3-Methylamino-4-nitrophenoxyethanol COLIPA n° B58; OPINION_NUMBER=SCCP/1089/07; COMMITTEE=Scientific Committee on Consumer Products (SCCP); REPORT_DATE=2 October 2007; VALUE_TEXT=25; DOSE=Data on nitrosamine content is not provided General toxicity Based on lymphoid depletion in the thymus at 100 and 400 mg/kg bw in males, the NOAEL is set at 25 mg/kg bw per day (90-day study in rats).; EFFECT=ir dye formulations only. Physico-chemical properties The stability of the test substance in marketed products is not reported. The test substance is a secondary amine and thus is prone to nitrosation. It should not be used in combination with nitrosating substances. The nitrosamine content should be < 50 ppb. Data on nitrosamine content is not provided General toxicity Based on lymphoid depletion in the thymus at 100 and 400 mg/kg bw in males, the NOAEL is set at 25 mg/kg bw per day (90-day study in rats). The NOAEL for maternal toxicity was considered as 100 mg/kg/day and the NOAEL for developmental toxicity was 750 mg/kg/day in the present study. Irritation / sensitisation Under the conditions of the experiments, 3-methylamino-4-nitrophenoxy-ethanol was not irritant to rabbit skin. It showed minimal irritancy to rabbit eyes. 3-Methylamino-4- nitrophenoxy-ethanol was not shown to be a skin sensitizer in a LLNA study. Dermal absorption The number of replicates (8, 2 from each donor) is not in accordance with the SCCP Note; CITATION_NUMBERS=[]; DETAILS_JSON={"cas_number":"59820-63-2","citation":"","dose":"Data on nitrosamine content is not provided General toxicity Based on lymphoid depletion in the thymus at 100 and 400 mg/kg bw in males, the NOAEL is set at 25 mg/kg bw per day (90-day study in rats).","duration":"90-day","effect":"ir dye formulations only. Physico-chemical properties The stability of the test substance in marketed products is not reported. The test substance is a secondary amine and thus is prone to nitrosation. It should not be used in combination with nitrosating substances. The nitrosamine content should be < 50 ppb. Data on nitrosamine content is not provided General toxicity Based on lymphoid depletion in the thymus at 100 and 400 mg/kg bw in males, the NOAEL is set at 25 mg/kg bw per day (90-day study in rats). The NOAEL for maternal toxicity was considered as 100 mg/kg/day and the NOAEL for developmental toxicity was 750 mg/kg/day in the present study. Irritation / sensitisation Under the conditions of the experiments, 3-methylamino-4-nitrophenoxy-ethanol was not irritant to rabbit skin. It showed minimal irritancy to rabbit eyes. 3-Methylamino-4- nitrophenoxy-ethanol was not shown to be a skin sensitizer in a LLNA study. Dermal absorption The number of replicates (8, 2 from each donor) is not in accordance with the SCCP Note","endpoint":"developmental toxicity","ingredient":"3-Methylamino-4-nitrophenoxyethanol","loael_value":"","noael_unit":"mg/kg bw","noael_value":"25","page":20,"route":"dermal","species":"rat","study_id":"sccp_o_110_noael_012"}

sccp_o_110.pdf

SOURCE_SUBDIR=sccp_o_110; REPORT_TITLE=OPINION ON 3-Methylamino-4-nitrophenoxyethanol COLIPA n° B58; OPINION_NUMBER=SCCP/1089/07; COMMITTEE=Scientific Committee on Consumer Products (SCCP); REPORT_DATE=2 October 2007; VALUE_TEXT=100; DOSE=s were observed in dams at any dose level.; EFFECT=s were observed in dams at any dose level. At 750 mg/kg/day, higher pre-implantation loss was attributed to two outliers and was not considered treatment related. No other treatment-related changes in litter data or foetal examinations were noted. No anomalies or malformations of toxicological significance were observed. The results show a slight maternotoxic effect at 250 mg/kg/day and a moderate maternotoxic effect at 750 mg/kg/day. Neither embryotoxic nor teratogenic effects were observed at any dose level. The NOAEL for maternotoxicity was considered as 100 mg/kg/day and the NOAEL for developmental toxicity was 750 mg/kg/day in the present study for 3-methylamino-4- nitrophenoxy-ethanol. Ref.: 9 3.3.9. Toxicokinetics No data submitted 3.3.10. Photo-induced toxicity 3.3.10.1. Phototoxicity / photoirritation and photosensitisation No data submitted 3.3.10.2. Phototoxicity / photomutagenicity / photoclastogenicity No data submitted 3.3.11. Human data No data submitted 3.3.12. Special investigations No data submitted; CITATION=Ref.: 9 3; CITATION_NUMBERS=[9,3]; REFERENCE=Ref.: 9 3; DETAILS_JSON={"cas_number":"59820-63-2","citation":"Ref.: 9 3","dose":"s were observed in dams at any dose level.","duration":"developmental","effect":"s were observed in dams at any dose level. At 750 mg/kg/day, higher pre-implantation loss was attributed to two outliers and was not considered treatment related. No other treatment-related changes in litter data or foetal examinations were noted. No anomalies or malformations of toxicological significance were observed. The results show a slight maternotoxic effect at 250 mg/kg/day and a moderate maternotoxic effect at 750 mg/kg/day. Neither embryotoxic nor teratogenic effects were observed at any dose level. The NOAEL for maternotoxicity was considered as 100 mg/kg/day and the NOAEL for developmental toxicity was 750 mg/kg/day in the present study for 3-methylamino-4- nitrophenoxy-ethanol. Ref.: 9 3.3.9. Toxicokinetics No data submitted 3.3.10. Photo-induced toxicity 3.3.10.1. Phototoxicity / photoirritation and photosensitisation No data submitted 3.3.10.2. Phototoxicity / photomutagenicity / photoclastogenicity No data submitted 3.3.11. Human data No data submitted 3.3.12. Special investigations No data submitted","endpoint":"developmental toxicity","ingredient":"3-Methylamino-4-nitrophenoxyethanol","loael_value":"","noael_unit":"mg/kg/day","noael_value":"100","page":19,"route":"","species":"human","study_id":"sccp_o_110_noael_006"}

sccp_o_110.pdf

SOURCE_SUBDIR=sccp_o_110; REPORT_TITLE=OPINION ON 3-Methylamino-4-nitrophenoxyethanol COLIPA n° B58; OPINION_NUMBER=SCCP/1089/07; COMMITTEE=Scientific Committee on Consumer Products (SCCP); REPORT_DATE=2 October 2007; VALUE_TEXT=100; DOSE=The results show a slight maternotoxic effect at 250 mg/kg/day and a moderate maternotoxic effect at 750 mg/kg/day.; EFFECT=r pre-implantation loss was attributed to two outliers and was not considered treatment related. No other treatment-related changes in litter data or foetal examinations were noted. No anomalies or malformations of toxicological significance were observed. The results show a slight maternotoxic effect at 250 mg/kg/day and a moderate maternotoxic effect at 750 mg/kg/day. Neither embryotoxic nor teratogenic effects were observed at any dose level. The NOAEL for maternotoxicity was considered as 100 mg/kg/day and the NOAEL for developmental toxicity was 750 mg/kg/day in the present study for 3-methylamino-4- nitrophenoxy-ethanol. Ref.: 9 3.3.9. Toxicokinetics No data submitted 3.3.10. Photo-induced toxicity 3.3.10.1. Phototoxicity / photoirritation and photosensitisation No data submitted 3.3.10.2. Phototoxicity / photomutagenicity / photoclastogenicity No data submitted 3.3.11. Human data No data submitted 3.3.12. Special investigations No data submitted 3.3.13. Safety evaluation (including calculation of the MoS) CALC; CITATION=Ref.: 9 3; CITATION_NUMBERS=[9,3]; REFERENCE=Ref.: 9 3; DETAILS_JSON={"cas_number":"59820-63-2","citation":"Ref.: 9 3","dose":"The results show a slight maternotoxic effect at 250 mg/kg/day and a moderate maternotoxic effect at 750 mg/kg/day.","duration":"developmental","effect":"r pre-implantation loss was attributed to two outliers and was not considered treatment related. No other treatment-related changes in litter data or foetal examinations were noted. No anomalies or malformations of toxicological significance were observed. The results show a slight maternotoxic effect at 250 mg/kg/day and a moderate maternotoxic effect at 750 mg/kg/day. Neither embryotoxic nor teratogenic effects were observed at any dose level. The NOAEL for maternotoxicity was considered as 100 mg/kg/day and the NOAEL for developmental toxicity was 750 mg/kg/day in the present study for 3-methylamino-4- nitrophenoxy-ethanol. Ref.: 9 3.3.9. Toxicokinetics No data submitted 3.3.10. Photo-induced toxicity 3.3.10.1. Phototoxicity / photoirritation and photosensitisation No data submitted 3.3.10.2. Phototoxicity / photomutagenicity / photoclastogenicity No data submitted 3.3.11. Human data No data submitted 3.3.12. Special investigations No data submitted 3.3.13. Safety evaluation (including calculation of the MoS) CALC","endpoint":"developmental toxicity","ingredient":"3-Methylamino-4-nitrophenoxyethanol","loael_value":"","noael_unit":"mg/kg/day","noael_value":"100","page":19,"route":"","species":"human","study_id":"sccp_o_110_noael_007"}

sccp_o_110.pdf

SOURCE_SUBDIR=sccp_o_110; REPORT_TITLE=OPINION ON 3-Methylamino-4-nitrophenoxyethanol COLIPA n° B58; OPINION_NUMBER=SCCP/1089/07; COMMITTEE=Scientific Committee on Consumer Products (SCCP); REPORT_DATE=2 October 2007; VALUE_TEXT=100; DOSE=Data on nitrosamine content is not provided General toxicity Based on lymphoid depletion in the thymus at 100 and 400 mg/kg bw in males, the NOAEL is set at 25 mg/kg bw per day (90-day study in rats).; EFFECT=of the test substance in marketed products is not reported. The test substance is a secondary amine and thus is prone to nitrosation. It should not be used in combination with nitrosating substances. The nitrosamine content should be < 50 ppb. Data on nitrosamine content is not provided General toxicity Based on lymphoid depletion in the thymus at 100 and 400 mg/kg bw in males, the NOAEL is set at 25 mg/kg bw per day (90-day study in rats). The NOAEL for maternal toxicity was considered as 100 mg/kg/day and the NOAEL for developmental toxicity was 750 mg/kg/day in the present study. Irritation / sensitisation Under the conditions of the experiments, 3-methylamino-4-nitrophenoxy-ethanol was not irritant to rabbit skin. It showed minimal irritancy to rabbit eyes. 3-Methylamino-4- nitrophenoxy-ethanol was not shown to be a skin sensitizer in a LLNA study. Dermal absorption The number of replicates (8, 2 from each donor) is not in accordance with the SCCP Notes of Guidance. However, the study was well conducted and therefore,; CITATION_NUMBERS=[]; DETAILS_JSON={"cas_number":"59820-63-2","citation":"","dose":"Data on nitrosamine content is not provided General toxicity Based on lymphoid depletion in the thymus at 100 and 400 mg/kg bw in males, the NOAEL is set at 25 mg/kg bw per day (90-day study in rats).","duration":"90-day","effect":"of the test substance in marketed products is not reported. The test substance is a secondary amine and thus is prone to nitrosation. It should not be used in combination with nitrosating substances. The nitrosamine content should be < 50 ppb. Data on nitrosamine content is not provided General toxicity Based on lymphoid depletion in the thymus at 100 and 400 mg/kg bw in males, the NOAEL is set at 25 mg/kg bw per day (90-day study in rats). The NOAEL for maternal toxicity was considered as 100 mg/kg/day and the NOAEL for developmental toxicity was 750 mg/kg/day in the present study. Irritation / sensitisation Under the conditions of the experiments, 3-methylamino-4-nitrophenoxy-ethanol was not irritant to rabbit skin. It showed minimal irritancy to rabbit eyes. 3-Methylamino-4- nitrophenoxy-ethanol was not shown to be a skin sensitizer in a LLNA study. Dermal absorption The number of replicates (8, 2 from each donor) is not in accordance with the SCCP Notes of Guidance. However, the study was well conducted and therefore,","endpoint":"developmental toxicity","ingredient":"3-Methylamino-4-nitrophenoxyethanol","loael_value":"","noael_unit":"mg/kg/day","noael_value":"100","page":20,"route":"dermal","species":"rat","study_id":"sccp_o_110_noael_013"}

sccp_o_110.pdf

SOURCE_SUBDIR=sccp_o_110; REPORT_TITLE=OPINION ON 3-Methylamino-4-nitrophenoxyethanol COLIPA n° B58; OPINION_NUMBER=SCCP/1089/07; COMMITTEE=Scientific Committee on Consumer Products (SCCP); REPORT_DATE=2 October 2007; VALUE_TEXT=300; DOSE=25 mated female per dose (20 pregnant per dose) Test substance:; EFFECT=al Developmental Toxicity Guideline: OECD 414 Species/strain: Rat, Sprague-Dawley Crl CD ( SD) BR Group size: 25 mated female per dose (20 pregnant per dose) Test substance: Imexine FR Batch: op 67 Purity: 99.8% Dose: 0, 100, 250 or 750 mg/kg/day Vehicle: 0.5% aqueous carboxymethylcellulose Route: gavage, 5 ml/kg/day Exposure: Gestation day (GD) 6-15 GLP: in compliance Dose levels for this study were selected based on the results of the preliminary embryo- foetal developmental toxicity study in rats in which the NOEL was 300 mg/kg/day [14]. Animals were observed twice daily for mortality/morbidity. Clinical signs were checked once daily. Food consumption and body weight were recorded at designated intervals during gestation. On day 20 of gestation, the animals were killed and examined macroscopically. Foetuses were removed by Caesarean section. The following litter parameters were recorded: number of corpora lutea, number of implantation sites, number and distribution of early and late resorptions, and number of dead and live; CITATION_NUMBERS=[]; DETAILS_JSON={"cas_number":"59820-63-2","citation":"","dose":"25 mated female per dose (20 pregnant per dose) Test substance:","duration":"Developmental","effect":"al Developmental Toxicity Guideline: OECD 414 Species/strain: Rat, Sprague-Dawley Crl CD ( SD) BR Group size: 25 mated female per dose (20 pregnant per dose) Test substance: Imexine FR Batch: op 67 Purity: 99.8% Dose: 0, 100, 250 or 750 mg/kg/day Vehicle: 0.5% aqueous carboxymethylcellulose Route: gavage, 5 ml/kg/day Exposure: Gestation day (GD) 6-15 GLP: in compliance Dose levels for this study were selected based on the results of the preliminary embryo- foetal developmental toxicity study in rats in which the NOEL was 300 mg/kg/day [14]. Animals were observed twice daily for mortality/morbidity. Clinical signs were checked once daily. Food consumption and body weight were recorded at designated intervals during gestation. On day 20 of gestation, the animals were killed and examined macroscopically. Foetuses were removed by Caesarean section. The following litter parameters were recorded: number of corpora lutea, number of implantation sites, number and distribution of early and late resorptions, and number of dead and live","endpoint":"developmental toxicity","ingredient":"3-Methylamino-4-nitrophenoxyethanol","loael_value":"","noael_unit":"mg/kg/day","noael_value":"300","page":18,"route":"oral","species":"rat","study_id":"sccp_o_110_noael_005"}

sccp_o_110.pdf

SOURCE_SUBDIR=sccp_o_110; REPORT_TITLE=OPINION ON 3-Methylamino-4-nitrophenoxyethanol COLIPA n° B58; OPINION_NUMBER=SCCP/1089/07; COMMITTEE=Scientific Committee on Consumer Products (SCCP); REPORT_DATE=2 October 2007; VALUE_TEXT=25; DOSE=Higher glucose, phosphorus, urea, bilirubin, cholesterol, triglyceride, alkaline phosphatase, ASAT and ALAT levels as well as lower blood sodium, potassium and chloride levels were observed in some animals of both sexes at 400 mg/kg/day.; EFFECT=ome animals. Higher glucose, phosphorus, urea, bilirubin, cholesterol, triglyceride, alkaline phosphatase, ASAT and ALAT levels as well as lower blood sodium, potassium and chloride levels were observed in some animals of both sexes at 400 mg/kg/day. Higher urine volume and glucosuria were also observed at this dose level. The study authors considered the NOAEL to be 100 mg/kg/day. Ref.: 5 Comment The SCCP considered the lymphoid depletion in the thymus at 100 and 400 mg/kg bw in males as adverse. Therefore, the NOAEL was set at 25 mg/kg bw per day. 3.3.5.3. Chronic (> 12 months) toxicity No data submitted 3.3.6. Mutagenicity / Genotoxicity 3.3.6.1 Mutagenicity / Genotoxicity in vitro Bacterial gene mutation assay Guideline: OECD 471 Species/strain: Salmonella typhimurium TA98, TA100, TA1535, and TA1537 Escherichia coli WP2uvrA Replicates: triplicates in 2 individual experiments both in the presence and absence of metabolic activation. Test substance: Imexine FR (3-methylamino-4-nitrophenoxy-ethanol) Solvent: DMSO Batch:; CITATION=Ref.: 5 Comment The SCCP considered the lymphoid depletion in the thymus at 100 and 400 mg/kg bw in males as adverse; CITATION_NUMBERS=[5,100,400]; REFERENCE=Ref.: 5 Comment The SCCP considered the lymphoid depletion in the thymus at 100 and 400 mg/kg bw in males as adverse; DETAILS_JSON={"cas_number":"59820-63-2","citation":"Ref.: 5 Comment The SCCP considered the lymphoid depletion in the thymus at 100 and 400 mg/kg bw in males as adverse","dose":"Higher glucose, phosphorus, urea, bilirubin, cholesterol, triglyceride, alkaline phosphatase, ASAT and ALAT levels as well as lower blood sodium, potassium and chloride levels were observed in some animals of both sexes at 400 mg/kg/day.","duration":"Chronic","effect":"ome animals. Higher glucose, phosphorus, urea, bilirubin, cholesterol, triglyceride, alkaline phosphatase, ASAT and ALAT levels as well as lower blood sodium, potassium and chloride levels were observed in some animals of both sexes at 400 mg/kg/day. Higher urine volume and glucosuria were also observed at this dose level. The study authors considered the NOAEL to be 100 mg/kg/day. Ref.: 5 Comment The SCCP considered the lymphoid depletion in the thymus at 100 and 400 mg/kg bw in males as adverse. Therefore, the NOAEL was set at 25 mg/kg bw per day. 3.3.5.3. Chronic (> 12 months) toxicity No data submitted 3.3.6. Mutagenicity / Genotoxicity 3.3.6.1 Mutagenicity / Genotoxicity in vitro Bacterial gene mutation assay Guideline: OECD 471 Species/strain: Salmonella typhimurium TA98, TA100, TA1535, and TA1537 Escherichia coli WP2uvrA Replicates: triplicates in 2 individual experiments both in the presence and absence of metabolic activation. Test substance: Imexine FR (3-methylamino-4-nitrophenoxy-ethanol) Solvent: DMSO Batch:","endpoint":"genotoxicity","ingredient":"3-Methylamino-4-nitrophenoxyethanol","loael_value":"","noael_unit":"mg/kg bw","noael_value":"25","page":15,"route":"","species":"","study_id":"sccp_o_110_noael_004"}

sccp_o_110.pdf

SOURCE_SUBDIR=sccp_o_110; REPORT_TITLE=OPINION ON 3-Methylamino-4-nitrophenoxyethanol COLIPA n° B58; OPINION_NUMBER=SCCP/1089/07; COMMITTEE=Scientific Committee on Consumer Products (SCCP); REPORT_DATE=2 October 2007; VALUE_TEXT=100; DOSE=Higher glucose, phosphorus, urea, bilirubin, cholesterol, triglyceride, alkaline phosphatase, ASAT and ALAT levels as well as lower blood sodium, potassium and chloride levels were observed in some animals of both sexes at 400 mg/kg/day.; EFFECT=ation (+13%), packed cell volume (+11%) and fibrinogen levels (+30%); these were considered signs of haemoconcentration caused by the dehydratation observed in some animals. Higher glucose, phosphorus, urea, bilirubin, cholesterol, triglyceride, alkaline phosphatase, ASAT and ALAT levels as well as lower blood sodium, potassium and chloride levels were observed in some animals of both sexes at 400 mg/kg/day. Higher urine volume and glucosuria were also observed at this dose level. The study authors considered the NOAEL to be 100 mg/kg/day. Ref.: 5 Comment The SCCP considered the lymphoid depletion in the thymus at 100 and 400 mg/kg bw in males as adverse. Therefore, the NOAEL was set at 25 mg/kg bw per day. 3.3.5.3. Chronic (> 12 months) toxicity No data submitted 3.3.6. Mutagenicity / Genotoxicity 3.3.6.1 Mutagenicity / Genotoxicity in vitro Bacterial gene mutation assay Guideline: OECD 471 Species/strain: Salmonella typhimurium TA98, TA100, TA1535, and TA1537 Escherichia coli WP2uvrA Replicates: triplicates in 2 individ; CITATION=Ref.: 5 Comment The SCCP considered the lymphoid depletion in the thymus at 100 and 400 mg/kg bw in males as adverse; CITATION_NUMBERS=[5,100,400]; REFERENCE=Ref.: 5 Comment The SCCP considered the lymphoid depletion in the thymus at 100 and 400 mg/kg bw in males as adverse; DETAILS_JSON={"cas_number":"59820-63-2","citation":"Ref.: 5 Comment The SCCP considered the lymphoid depletion in the thymus at 100 and 400 mg/kg bw in males as adverse","dose":"Higher glucose, phosphorus, urea, bilirubin, cholesterol, triglyceride, alkaline phosphatase, ASAT and ALAT levels as well as lower blood sodium, potassium and chloride levels were observed in some animals of both sexes at 400 mg/kg/day.","duration":"Chronic","effect":"ation (+13%), packed cell volume (+11%) and fibrinogen levels (+30%); these were considered signs of haemoconcentration caused by the dehydratation observed in some animals. Higher glucose, phosphorus, urea, bilirubin, cholesterol, triglyceride, alkaline phosphatase, ASAT and ALAT levels as well as lower blood sodium, potassium and chloride levels were observed in some animals of both sexes at 400 mg/kg/day. Higher urine volume and glucosuria were also observed at this dose level. The study authors considered the NOAEL to be 100 mg/kg/day. Ref.: 5 Comment The SCCP considered the lymphoid depletion in the thymus at 100 and 400 mg/kg bw in males as adverse. Therefore, the NOAEL was set at 25 mg/kg bw per day. 3.3.5.3. Chronic (> 12 months) toxicity No data submitted 3.3.6. Mutagenicity / Genotoxicity 3.3.6.1 Mutagenicity / Genotoxicity in vitro Bacterial gene mutation assay Guideline: OECD 471 Species/strain: Salmonella typhimurium TA98, TA100, TA1535, and TA1537 Escherichia coli WP2uvrA Replicates: triplicates in 2 individ","endpoint":"genotoxicity","ingredient":"3-Methylamino-4-nitrophenoxyethanol","loael_value":"","noael_unit":"mg/kg/day","noael_value":"100","page":15,"route":"","species":"","study_id":"sccp_o_110_noael_003"}

sccp_o_110.pdf