NOAEL Studies Cosmetic Ingredient

HC Orange No. 1 NOAEL Studies

INCI: HC ORANGE NO. 1

CAS: 54381-08-7

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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CIR Safety Assessment 3 endpoints
Source Endpoint Type Value Unit Species Route Duration Study Type Reference
CIR Safety Assessment DERMAL_ABSORPTION =1.28 % human (cadaver skin, in vitro) dermal - Static horizontal diffusion cells using human female cadaver split-thickness skin; 14C-HC Orange No. 1 (specific activity: 38.1 pc/mg) mixed with nonradioactive HC Orange No. 1 in hair dye base at 1.0% concentration (0.130 µCi/mg); applied at 10 mg/cm² for 30 min then rinsed; receptor fluid sampled at 1, 2, 4, 6, 8, 24, 30, and 48 hours {"absorption_percent":"1.28 ± 0.96% at 24 hours; 1.41 ± 0.96% at 48 hours","citation":"Clairol Research & Development Laboratories 1994","page":4,"pdf":"PRS41.pdf","row_type":"dermal_absorption_study"}
CIR Safety Assessment DERMAL_ABSORPTION =1.28 % human (cadaver skin, in vitro) dermal - Static horizontal diffusion cells using human female cadaver split-thickness skin; 14C-HC Orange No. 1 (specific activity: 38.1 pc/mg) mixed with nonradioactive HC Orange No. 1 in hair dye base at 1.0% concentration (0.130 µCi/mg); applied at 10 mg/cm² for 30 min then rinsed; receptor fluid sampled at 1, 2, 4, 6, 8, 24, 30, and 48 hours {"absorption_percent":"1.28 ± 0.96% at 24 hours; 1.41 ± 0.96% at 48 hours","citation":"Clairol Research & Development Laboratories 1994","page":4,"pdf":"PRS41.pdf","row_type":"dermal_absorption_study"}
CIR Safety Assessment DERMAL_ABSORPTION =1.28 % human (cadaver skin, in vitro) dermal - Static horizontal diffusion cells using human female cadaver split-thickness skin; 14C-HC Orange No. 1 (specific activity: 38.1 pc/mg) mixed with nonradioactive HC Orange No. 1 in hair dye base at 1.0% concentration (0.130 µCi/mg); applied at 10 mg/cm² for 30 min then rinsed; receptor fluid sampled at 1, 2, 4, 6, 8, 24, 30, and 48 hours {"absorption_percent":"1.28 ± 0.96% at 24 hours; 1.41 ± 0.96% at 48 hours","citation":"Clairol Research & Development Laboratories 1994","page":4,"pdf":"PRS41.pdf","row_type":"dermal_absorption_study"}
COSMOS DB 1 endpoint
Source Endpoint Type Value Unit Species Route Duration Study Type Reference
COSMOS DB LOAEL 2.5 mg/kg bw/day rat oral 91 day Subchronic SCCP; Henwood S. M. 91-Day Oral Gavage Toxicity Study With GTS03977 In Rats With A 4-Week Recovery Period, P&G Study #2749-53922, September 2005
SCCS Opinion 36 endpoints
Source Endpoint Type Value Unit Species Route Duration Study Type Reference
SCCS Opinion NOAEL =750 mg/kg/day rat oral Sub-chronic repeated dose toxicity {"citation":"Ref.: 10 Comment This was a range-finding study","dose":"These increases were considered dose related and possibly adverse.","effect":"The increases in liver- and kidney-to-body weight percentages were statistically significant. These increases were considered dose related and possibly adverse. There were no dose-related macroscopic observations. The toxicological significance of clinical pathological changes at mid-high and high doses could not be determined since though the tissues were preserved, no histopathology was performed. Based on relative changes in liver and kidney weights and related clinical pathology findings at 750 mg/kg/day, the NOAEL following oral gavage of GTS03977 was considered to be 300 mg/kg/day. Ref.: 10 Comment This was a range-finding study. The NOAEL of 300 mg/kg/day was derived without assessing the histopathology. 3.3.5.2. Sub-chronic (90 days) oral / dermal / inhalation toxicity Guideline: OECD 408 (1998) Species/strain: Rat, Sprague Dawley Crl:CD IGS BR Group size: 5 per dose/sex; 50 in total Test substance: GTS03977 Batch: # 32 Purity: 100.3% Dose: 0, 2.5, 10, 25 mg/kg bw/day Route: oral gavage Volume/Vehicle: 5 mL/kg in poly","page":15,"pdf":"sccp_o_146.pdf","row_type":"noael_study","study_id":"sccp_o_146_noael_001"}
SCCS Opinion NOAEL =300 mg/kg/day rat oral Sub-chronic repeated dose toxicity {"citation":"Ref.: 10 Comment This was a range-finding study","dose":"There were no dose-related macroscopic observations.","effect":"related and possibly adverse. There were no dose-related macroscopic observations. The toxicological significance of clinical pathological changes at mid-high and high doses could not be determined since though the tissues were preserved, no histopathology was performed. Based on relative changes in liver and kidney weights and related clinical pathology findings at 750 mg/kg/day, the NOAEL following oral gavage of GTS03977 was considered to be 300 mg/kg/day. Ref.: 10 Comment This was a range-finding study. The NOAEL of 300 mg/kg/day was derived without assessing the histopathology. 3.3.5.2. Sub-chronic (90 days) oral / dermal / inhalation toxicity Guideline: OECD 408 (1998) Species/strain: Rat, Sprague Dawley Crl:CD IGS BR Group size: 5 per dose/sex; 50 in total Test substance: GTS03977 Batch: # 32 Purity: 100.3% Dose: 0, 2.5, 10, 25 mg/kg bw/day Route: oral gavage Volume/Vehicle: 5 mL/kg in polyethylene glycol 400 Exposure: 91 days Recovery period: 4 weeks GLP: in compliance Date: 13.09.2005 The animals were observed twic","page":15,"pdf":"sccp_o_146.pdf","row_type":"noael_study","study_id":"sccp_o_146_noael_002"}
SCCS Opinion NOAEL =25 mg/kg bw/d - - Chronic carcinogenicity {"citation":"Ref.: 11 Comment According the OECD guidelines, the highest dose should induce toxicity","dose":"There was a dose-related increase in the incidence of orange staining of fur and skin in animals dosed at 10 or 25 mg/kg/day.","effect":"mean body weights, body weight changes, or food consumption were observed. There was a dose-related increase in the incidence of orange staining of fur and skin in animals dosed at 10 or 25 mg/kg/day. Urine was darker or discoloured for males at all dose levels and females given 10 or 25 mg/kg/day. No other clear effects on clinical pathology test were recorded. Conclusion There were no other statistically significant treatment-related effects in any dose group at the end of the treatment and recovery phases. The NOAEL for GTS03977was determined to be 25 mg/kg bw/d in this study. Ref.: 11 Comment According the OECD guidelines, the highest dose should induce toxicity. 3.3.5.3. Chronic (> 12 months) toxicity See 3.3.7. Carcinogenicity 3.3.6. Mutagenicity / Genotoxicity 3.3.6.1 Mutagenicity / Genotoxicity in vitro Bacterial Reverse Mutation Test Guideline: OECD 471 Species/strain: Salmonella typhimurium TA98, TA100, TA1535, TA1537 and Escherichia coli WP2uvrA (pKM101) Replicates: duplicates or triplicates in 2 individual exp","page":16,"pdf":"sccp_o_146.pdf","row_type":"noael_study","study_id":"sccp_o_146_noael_003"}
SCCS Opinion NOAEL =75 mg/kg/day - oral developmental developmental toxicity {"citation":"Ref.: 18","dose":"Foetal parameters No gross external, soft tissue or skeletal alterations (malformations or variations) were caused by doses as high as 250 mg/kg/day.","effect":"roken incisors. Foetal parameters No gross external, soft tissue or skeletal alterations (malformations or variations) were caused by doses as high as 250 mg/kg/day. There were no dosage-dependent, significant differences in the litter or foetal incidences of any gross external, soft tissue or skeletal alterations. Ossification site averages were comparable among the groups and no biologically important differences occurred. Conclusions On the basis of these data, the maternal no-observable-adverse-effect-level (NOAEL) for HC Orange n° 1 (GTS03977) is 75 mg/kg/day (the 250 mg/kg/day dosage produced clinical signs of rales and decreases in body weight, body weight gain and absolute feed consumption). The developmental NOAEL of GTS03977 is 250 mg/kg/day (no effects were observed at the highest dose tested). Ref.: 18","page":26,"pdf":"sccp_o_146.pdf","row_type":"noael_study","study_id":"sccp_o_146_noael_004"}
SCCS Opinion NOAEL =250 mg/kg/day - oral developmental developmental toxicity {"citation":"Ref.: 18","dose":"Conclusions On the basis of these data, the maternal no-observable-adverse-effect-level (NOAEL) for HC Orange n° 1 (GTS03977) is 75 mg/kg/day (the 250 mg/kg/day dosage produced clinical signs of rales and decreases in body weight, body weight gain and absolute feed consumption).","effect":"t differences in the litter or foetal incidences of any gross external, soft tissue or skeletal alterations. Ossification site averages were comparable among the groups and no biologically important differences occurred. Conclusions On the basis of these data, the maternal no-observable-adverse-effect-level (NOAEL) for HC Orange n° 1 (GTS03977) is 75 mg/kg/day (the 250 mg/kg/day dosage produced clinical signs of rales and decreases in body weight, body weight gain and absolute feed consumption). The developmental NOAEL of GTS03977 is 250 mg/kg/day (no effects were observed at the highest dose tested). Ref.: 18","page":26,"pdf":"sccp_o_146.pdf","row_type":"noael_study","study_id":"sccp_o_146_noael_005"}
SCCS Opinion NOAEL =0.15 % rat dermal 13 week developmental toxicity {"citation":"Ref.: 19 Comment This study indicates that HC Orange No1 in this hair dye formulation is not teratogenic","dose":"There were no significant differences in body weight gain or food consumption in treated animals versus the negative control groups The number of corpora lutea, implantations, resorptions and abortions were similar to the negative controls.","effect":"ed. No signs of irritation were noted. No signs of toxicity were seen throughout the study. There were no significant differences in body weight gain or food consumption in treated animals versus the negative control groups The number of corpora lutea, implantations, resorptions and abortions were similar to the negative controls. Foetal parameters: The sex ratio and number of live foetuses, dead or resorbed foetuses resorptions and foetal abnormalities were similar to the negative controls. A maternal and foetal NOAEL in this hair dye formulation was derived of 0.15% HC Orange #1. Ref.: 19 Comment This study indicates that HC Orange No1 in this hair dye formulation is not teratogenic. Included in this publication was a 13 week topical application study on New Zealand white rabbit that suggested that the use of this hair dye formulation twice a week, at the same concentrations as in the above rat study, had no toxic effect. 3.3.9. Toxicokinetics No data submitted 3.3.10. Photo-induced toxicity No data submitted 3.3.11. Hum","page":27,"pdf":"sccp_o_146.pdf","row_type":"noael_study","study_id":"sccp_o_146_noael_006"}
SCCS Opinion NOAEL =0.024 mg/kg bw rat oral 90-day dermal absorption {"dose":"Safety evaluation (including calculation of the MoS) CALCULATION OF THE MARGIN OF SAFETY (HC Orange n° 1) (Non-oxidative / semi-permanent) Maximum absorption through the skin A (μg/cm2) = 2.06 µg/cm² Skin Area surface SAS (cm2) = 700 cm2 Dermal absorption per treatment SAS x A x 0.001 = 1.442 mg Typical body weight of human = 60 kg Systemic expo...","effect":"SCCP/1164/08 Opinion on HC Orange n° 1 28 3.3.13. Safety evaluation (including calculation of the MoS) CALCULATION OF THE MARGIN OF SAFETY (HC Orange n° 1) (Non-oxidative / semi-permanent) Maximum absorption through the skin A (μg/cm2) = 2.06 µg/cm² Skin Area surface SAS (cm2) = 700 cm2 Dermal absorption per treatment SAS x A x 0.001 = 1.442 mg Typical body weight of human = 60 kg Systemic exposure dose (SED) SAS x A x 0.001/60 = 0.024 mg/kg bw No observed adverse effect level NOAEL = 25 mg/kg bw (90-day, oral, rat) Margin of Safety NOAEL / SED = 1042 3.3.14. Discussion Physico-chemical properties HC Orange n° 1 is used as an ingredient in non-oxidative hair dye formulations at levels up to 1%. The stability of HC Orange n° 1 in marketed products is not described. Only one batch of HC Orange n° 1 has been analyzed and characterized. Calculated values of Log Pow cannot be accepted as an estimate of the true physical constant without justification. The absolute content of the dye in a","page":28,"pdf":"sccp_o_146.pdf","row_type":"noael_study","study_id":"sccp_o_146_noael_007"}
SCCS Opinion NOAEL =25 mg/kg bw rat oral 90-day dermal absorption {"dose":"Safety evaluation (including calculation of the MoS) CALCULATION OF THE MARGIN OF SAFETY (HC Orange n° 1) (Non-oxidative / semi-permanent) Maximum absorption through the skin A (μg/cm2) = 2.06 µg/cm² Skin Area surface SAS (cm2) = 700 cm2 Dermal absorption per treatment SAS x A x 0.001 = 1.442 mg Typical body weight of human = 60 kg Systemic expo...","effect":"SCCP/1164/08 Opinion on HC Orange n° 1 28 3.3.13. Safety evaluation (including calculation of the MoS) CALCULATION OF THE MARGIN OF SAFETY (HC Orange n° 1) (Non-oxidative / semi-permanent) Maximum absorption through the skin A (μg/cm2) = 2.06 µg/cm² Skin Area surface SAS (cm2) = 700 cm2 Dermal absorption per treatment SAS x A x 0.001 = 1.442 mg Typical body weight of human = 60 kg Systemic exposure dose (SED) SAS x A x 0.001/60 = 0.024 mg/kg bw No observed adverse effect level NOAEL = 25 mg/kg bw (90-day, oral, rat) Margin of Safety NOAEL / SED = 1042 3.3.14. Discussion Physico-chemical properties HC Orange n° 1 is used as an ingredient in non-oxidative hair dye formulations at levels up to 1%. The stability of HC Orange n° 1 in marketed products is not described. Only one batch of HC Orange n° 1 has been analyzed and characterized. Calculated values of Log Pow cannot be accepted as an estimate of the true physical constant without justification. The absolute content of the dye in any of","page":28,"pdf":"sccp_o_146.pdf","row_type":"noael_study","study_id":"sccp_o_146_noael_008"}
SCCS Opinion NOAEL =75 mg/kg bw/day guinea pig - developmental reproductive toxicity {"dose":"General toxicity The no-observable-adverse-effect-level (NOAEL) for HC Orange n° 1 was determined to be 25 mg/kg bw/d in the 90 study.","effect":"levels up to 1%. The stability of HC Orange n° 1 in marketed products is not described. Only one batch of HC Orange n° 1 has been analyzed and characterized. Calculated values of Log Pow cannot be accepted as an estimate of the true physical constant without justification. The absolute content of the dye in any of the batches used is not reported. General toxicity The no-observable-adverse-effect-level (NOAEL) for HC Orange n° 1 was determined to be 25 mg/kg bw/d in the 90 study. In the reproductive studies, the NOAEL for maternal toxicity was 75 mg/kg bw/day and 250 mg/kg bw/day for developmental toxicity. Irritation / sensitisation Under the test conditions, HC Orange n° 1 was not a skin irritant. HC Orange n° 1 is considered to have the potential to produce transient mild eye irritation. No evidence of sensitisation was observed in a Guinea Pig Maximisation Test. It did not induce a hypersensitivity response in an LLNA. However, as the tested concentrations were too low, a skin sensitising potential cannot be excluded. D","page":28,"pdf":"sccp_o_146.pdf","row_type":"noael_study","study_id":"sccp_o_146_noael_011"}
SCCS Opinion NOAEL =750 mg/kg/day rat oral Sub-chronic repeated dose toxicity {"citation":"Ref.: 10 Comment This was a range-finding study","dose":"These increases were considered dose related and possibly adverse.","effect":"The increases in liver- and kidney-to-body weight percentages were statistically significant. These increases were considered dose related and possibly adverse. There were no dose-related macroscopic observations. The toxicological significance of clinical pathological changes at mid-high and high doses could not be determined since though the tissues were preserved, no histopathology was performed. Based on relative changes in liver and kidney weights and related clinical pathology findings at 750 mg/kg/day, the NOAEL following oral gavage of GTS03977 was considered to be 300 mg/kg/day. Ref.: 10 Comment This was a range-finding study. The NOAEL of 300 mg/kg/day was derived without assessing the histopathology. 3.3.5.2. Sub-chronic (90 days) oral / dermal / inhalation toxicity Guideline: OECD 408 (1998) Species/strain: Rat, Sprague Dawley Crl:CD IGS BR Group size: 5 per dose/sex; 50 in total Test substance: GTS03977 Batch: # 32 Purity: 100.3% Dose: 0, 2.5, 10, 25 mg/kg bw/day Route: oral gavage Volume/Vehicle: 5 mL/kg in poly","page":15,"pdf":"sccp_o_146.pdf","row_type":"noael_study","study_id":"sccp_o_146_noael_001"}
SCCS Opinion NOAEL =300 mg/kg/day rat oral Sub-chronic repeated dose toxicity {"citation":"Ref.: 10 Comment This was a range-finding study","dose":"There were no dose-related macroscopic observations.","effect":"related and possibly adverse. There were no dose-related macroscopic observations. The toxicological significance of clinical pathological changes at mid-high and high doses could not be determined since though the tissues were preserved, no histopathology was performed. Based on relative changes in liver and kidney weights and related clinical pathology findings at 750 mg/kg/day, the NOAEL following oral gavage of GTS03977 was considered to be 300 mg/kg/day. Ref.: 10 Comment This was a range-finding study. The NOAEL of 300 mg/kg/day was derived without assessing the histopathology. 3.3.5.2. Sub-chronic (90 days) oral / dermal / inhalation toxicity Guideline: OECD 408 (1998) Species/strain: Rat, Sprague Dawley Crl:CD IGS BR Group size: 5 per dose/sex; 50 in total Test substance: GTS03977 Batch: # 32 Purity: 100.3% Dose: 0, 2.5, 10, 25 mg/kg bw/day Route: oral gavage Volume/Vehicle: 5 mL/kg in polyethylene glycol 400 Exposure: 91 days Recovery period: 4 weeks GLP: in compliance Date: 13.09.2005 The animals were observed twic","page":15,"pdf":"sccp_o_146.pdf","row_type":"noael_study","study_id":"sccp_o_146_noael_002"}
SCCS Opinion NOAEL =25 mg/kg bw/d - - Chronic carcinogenicity {"citation":"Ref.: 11 Comment According the OECD guidelines, the highest dose should induce toxicity","dose":"There was a dose-related increase in the incidence of orange staining of fur and skin in animals dosed at 10 or 25 mg/kg/day.","effect":"mean body weights, body weight changes, or food consumption were observed. There was a dose-related increase in the incidence of orange staining of fur and skin in animals dosed at 10 or 25 mg/kg/day. Urine was darker or discoloured for males at all dose levels and females given 10 or 25 mg/kg/day. No other clear effects on clinical pathology test were recorded. Conclusion There were no other statistically significant treatment-related effects in any dose group at the end of the treatment and recovery phases. The NOAEL for GTS03977was determined to be 25 mg/kg bw/d in this study. Ref.: 11 Comment According the OECD guidelines, the highest dose should induce toxicity. 3.3.5.3. Chronic (> 12 months) toxicity See 3.3.7. Carcinogenicity 3.3.6. Mutagenicity / Genotoxicity 3.3.6.1 Mutagenicity / Genotoxicity in vitro Bacterial Reverse Mutation Test Guideline: OECD 471 Species/strain: Salmonella typhimurium TA98, TA100, TA1535, TA1537 and Escherichia coli WP2uvrA (pKM101) Replicates: duplicates or triplicates in 2 individual exp","page":16,"pdf":"sccp_o_146.pdf","row_type":"noael_study","study_id":"sccp_o_146_noael_003"}
SCCS Opinion NOAEL =75 mg/kg/day - oral developmental developmental toxicity {"citation":"Ref.: 18","dose":"Foetal parameters No gross external, soft tissue or skeletal alterations (malformations or variations) were caused by doses as high as 250 mg/kg/day.","effect":"roken incisors. Foetal parameters No gross external, soft tissue or skeletal alterations (malformations or variations) were caused by doses as high as 250 mg/kg/day. There were no dosage-dependent, significant differences in the litter or foetal incidences of any gross external, soft tissue or skeletal alterations. Ossification site averages were comparable among the groups and no biologically important differences occurred. Conclusions On the basis of these data, the maternal no-observable-adverse-effect-level (NOAEL) for HC Orange n° 1 (GTS03977) is 75 mg/kg/day (the 250 mg/kg/day dosage produced clinical signs of rales and decreases in body weight, body weight gain and absolute feed consumption). The developmental NOAEL of GTS03977 is 250 mg/kg/day (no effects were observed at the highest dose tested). Ref.: 18","page":26,"pdf":"sccp_o_146.pdf","row_type":"noael_study","study_id":"sccp_o_146_noael_004"}
SCCS Opinion NOAEL =250 mg/kg/day - oral developmental developmental toxicity {"citation":"Ref.: 18","dose":"Conclusions On the basis of these data, the maternal no-observable-adverse-effect-level (NOAEL) for HC Orange n° 1 (GTS03977) is 75 mg/kg/day (the 250 mg/kg/day dosage produced clinical signs of rales and decreases in body weight, body weight gain and absolute feed consumption).","effect":"t differences in the litter or foetal incidences of any gross external, soft tissue or skeletal alterations. Ossification site averages were comparable among the groups and no biologically important differences occurred. Conclusions On the basis of these data, the maternal no-observable-adverse-effect-level (NOAEL) for HC Orange n° 1 (GTS03977) is 75 mg/kg/day (the 250 mg/kg/day dosage produced clinical signs of rales and decreases in body weight, body weight gain and absolute feed consumption). The developmental NOAEL of GTS03977 is 250 mg/kg/day (no effects were observed at the highest dose tested). Ref.: 18","page":26,"pdf":"sccp_o_146.pdf","row_type":"noael_study","study_id":"sccp_o_146_noael_005"}
SCCS Opinion NOAEL =0.15 % rat dermal 13 week developmental toxicity {"citation":"Ref.: 19 Comment This study indicates that HC Orange No1 in this hair dye formulation is not teratogenic","dose":"There were no significant differences in body weight gain or food consumption in treated animals versus the negative control groups The number of corpora lutea, implantations, resorptions and abortions were similar to the negative controls.","effect":"ed. No signs of irritation were noted. No signs of toxicity were seen throughout the study. There were no significant differences in body weight gain or food consumption in treated animals versus the negative control groups The number of corpora lutea, implantations, resorptions and abortions were similar to the negative controls. Foetal parameters: The sex ratio and number of live foetuses, dead or resorbed foetuses resorptions and foetal abnormalities were similar to the negative controls. A maternal and foetal NOAEL in this hair dye formulation was derived of 0.15% HC Orange #1. Ref.: 19 Comment This study indicates that HC Orange No1 in this hair dye formulation is not teratogenic. Included in this publication was a 13 week topical application study on New Zealand white rabbit that suggested that the use of this hair dye formulation twice a week, at the same concentrations as in the above rat study, had no toxic effect. 3.3.9. Toxicokinetics No data submitted 3.3.10. Photo-induced toxicity No data submitted 3.3.11. Hum","page":27,"pdf":"sccp_o_146.pdf","row_type":"noael_study","study_id":"sccp_o_146_noael_006"}
SCCS Opinion NOAEL =0.024 mg/kg bw rat oral 90-day dermal absorption {"dose":"Safety evaluation (including calculation of the MoS) CALCULATION OF THE MARGIN OF SAFETY (HC Orange n° 1) (Non-oxidative / semi-permanent) Maximum absorption through the skin A (μg/cm2) = 2.06 µg/cm² Skin Area surface SAS (cm2) = 700 cm2 Dermal absorption per treatment SAS x A x 0.001 = 1.442 mg Typical body weight of human = 60 kg Systemic expo...","effect":"SCCP/1164/08 Opinion on HC Orange n° 1 28 3.3.13. Safety evaluation (including calculation of the MoS) CALCULATION OF THE MARGIN OF SAFETY (HC Orange n° 1) (Non-oxidative / semi-permanent) Maximum absorption through the skin A (μg/cm2) = 2.06 µg/cm² Skin Area surface SAS (cm2) = 700 cm2 Dermal absorption per treatment SAS x A x 0.001 = 1.442 mg Typical body weight of human = 60 kg Systemic exposure dose (SED) SAS x A x 0.001/60 = 0.024 mg/kg bw No observed adverse effect level NOAEL = 25 mg/kg bw (90-day, oral, rat) Margin of Safety NOAEL / SED = 1042 3.3.14. Discussion Physico-chemical properties HC Orange n° 1 is used as an ingredient in non-oxidative hair dye formulations at levels up to 1%. The stability of HC Orange n° 1 in marketed products is not described. Only one batch of HC Orange n° 1 has been analyzed and characterized. Calculated values of Log Pow cannot be accepted as an estimate of the true physical constant without justification. The absolute content of the dye in a","page":28,"pdf":"sccp_o_146.pdf","row_type":"noael_study","study_id":"sccp_o_146_noael_007"}
SCCS Opinion NOAEL =25 mg/kg bw rat oral 90-day dermal absorption {"dose":"Safety evaluation (including calculation of the MoS) CALCULATION OF THE MARGIN OF SAFETY (HC Orange n° 1) (Non-oxidative / semi-permanent) Maximum absorption through the skin A (μg/cm2) = 2.06 µg/cm² Skin Area surface SAS (cm2) = 700 cm2 Dermal absorption per treatment SAS x A x 0.001 = 1.442 mg Typical body weight of human = 60 kg Systemic expo...","effect":"SCCP/1164/08 Opinion on HC Orange n° 1 28 3.3.13. Safety evaluation (including calculation of the MoS) CALCULATION OF THE MARGIN OF SAFETY (HC Orange n° 1) (Non-oxidative / semi-permanent) Maximum absorption through the skin A (μg/cm2) = 2.06 µg/cm² Skin Area surface SAS (cm2) = 700 cm2 Dermal absorption per treatment SAS x A x 0.001 = 1.442 mg Typical body weight of human = 60 kg Systemic exposure dose (SED) SAS x A x 0.001/60 = 0.024 mg/kg bw No observed adverse effect level NOAEL = 25 mg/kg bw (90-day, oral, rat) Margin of Safety NOAEL / SED = 1042 3.3.14. Discussion Physico-chemical properties HC Orange n° 1 is used as an ingredient in non-oxidative hair dye formulations at levels up to 1%. The stability of HC Orange n° 1 in marketed products is not described. Only one batch of HC Orange n° 1 has been analyzed and characterized. Calculated values of Log Pow cannot be accepted as an estimate of the true physical constant without justification. The absolute content of the dye in any of","page":28,"pdf":"sccp_o_146.pdf","row_type":"noael_study","study_id":"sccp_o_146_noael_008"}
SCCS Opinion NOAEL =75 mg/kg bw/day guinea pig - developmental reproductive toxicity {"dose":"General toxicity The no-observable-adverse-effect-level (NOAEL) for HC Orange n° 1 was determined to be 25 mg/kg bw/d in the 90 study.","effect":"levels up to 1%. The stability of HC Orange n° 1 in marketed products is not described. Only one batch of HC Orange n° 1 has been analyzed and characterized. Calculated values of Log Pow cannot be accepted as an estimate of the true physical constant without justification. The absolute content of the dye in any of the batches used is not reported. General toxicity The no-observable-adverse-effect-level (NOAEL) for HC Orange n° 1 was determined to be 25 mg/kg bw/d in the 90 study. In the reproductive studies, the NOAEL for maternal toxicity was 75 mg/kg bw/day and 250 mg/kg bw/day for developmental toxicity. Irritation / sensitisation Under the test conditions, HC Orange n° 1 was not a skin irritant. HC Orange n° 1 is considered to have the potential to produce transient mild eye irritation. No evidence of sensitisation was observed in a Guinea Pig Maximisation Test. It did not induce a hypersensitivity response in an LLNA. However, as the tested concentrations were too low, a skin sensitising potential cannot be excluded. D","page":28,"pdf":"sccp_o_146.pdf","row_type":"noael_study","study_id":"sccp_o_146_noael_011"}
SCCS Opinion NOAEL =750 mg/kg/day rat oral Sub-chronic repeated dose toxicity {"citation":"Ref.: 10 Comment This was a range-finding study","dose":"These increases were considered dose related and possibly adverse.","effect":"The increases in liver- and kidney-to-body weight percentages were statistically significant. These increases were considered dose related and possibly adverse. There were no dose-related macroscopic observations. The toxicological significance of clinical pathological changes at mid-high and high doses could not be determined since though the tissues were preserved, no histopathology was performed. Based on relative changes in liver and kidney weights and related clinical pathology findings at 750 mg/kg/day, the NOAEL following oral gavage of GTS03977 was considered to be 300 mg/kg/day. Ref.: 10 Comment This was a range-finding study. The NOAEL of 300 mg/kg/day was derived without assessing the histopathology. 3.3.5.2. Sub-chronic (90 days) oral / dermal / inhalation toxicity Guideline: OECD 408 (1998) Species/strain: Rat, Sprague Dawley Crl:CD IGS BR Group size: 5 per dose/sex; 50 in total Test substance: GTS03977 Batch: # 32 Purity: 100.3% Dose: 0, 2.5, 10, 25 mg/kg bw/day Route: oral gavage Volume/Vehicle: 5 mL/kg in poly","page":15,"pdf":"sccp_o_146.pdf","row_type":"noael_study","study_id":"sccp_o_146_noael_001"}
SCCS Opinion NOAEL =300 mg/kg/day rat oral Sub-chronic repeated dose toxicity {"citation":"Ref.: 10 Comment This was a range-finding study","dose":"There were no dose-related macroscopic observations.","effect":"related and possibly adverse. There were no dose-related macroscopic observations. The toxicological significance of clinical pathological changes at mid-high and high doses could not be determined since though the tissues were preserved, no histopathology was performed. Based on relative changes in liver and kidney weights and related clinical pathology findings at 750 mg/kg/day, the NOAEL following oral gavage of GTS03977 was considered to be 300 mg/kg/day. Ref.: 10 Comment This was a range-finding study. The NOAEL of 300 mg/kg/day was derived without assessing the histopathology. 3.3.5.2. Sub-chronic (90 days) oral / dermal / inhalation toxicity Guideline: OECD 408 (1998) Species/strain: Rat, Sprague Dawley Crl:CD IGS BR Group size: 5 per dose/sex; 50 in total Test substance: GTS03977 Batch: # 32 Purity: 100.3% Dose: 0, 2.5, 10, 25 mg/kg bw/day Route: oral gavage Volume/Vehicle: 5 mL/kg in polyethylene glycol 400 Exposure: 91 days Recovery period: 4 weeks GLP: in compliance Date: 13.09.2005 The animals were observed twic","page":15,"pdf":"sccp_o_146.pdf","row_type":"noael_study","study_id":"sccp_o_146_noael_002"}
SCCS Opinion NOAEL =25 mg/kg bw/d - - Chronic carcinogenicity {"citation":"Ref.: 11 Comment According the OECD guidelines, the highest dose should induce toxicity","dose":"There was a dose-related increase in the incidence of orange staining of fur and skin in animals dosed at 10 or 25 mg/kg/day.","effect":"mean body weights, body weight changes, or food consumption were observed. There was a dose-related increase in the incidence of orange staining of fur and skin in animals dosed at 10 or 25 mg/kg/day. Urine was darker or discoloured for males at all dose levels and females given 10 or 25 mg/kg/day. No other clear effects on clinical pathology test were recorded. Conclusion There were no other statistically significant treatment-related effects in any dose group at the end of the treatment and recovery phases. The NOAEL for GTS03977was determined to be 25 mg/kg bw/d in this study. Ref.: 11 Comment According the OECD guidelines, the highest dose should induce toxicity. 3.3.5.3. Chronic (> 12 months) toxicity See 3.3.7. Carcinogenicity 3.3.6. Mutagenicity / Genotoxicity 3.3.6.1 Mutagenicity / Genotoxicity in vitro Bacterial Reverse Mutation Test Guideline: OECD 471 Species/strain: Salmonella typhimurium TA98, TA100, TA1535, TA1537 and Escherichia coli WP2uvrA (pKM101) Replicates: duplicates or triplicates in 2 individual exp","page":16,"pdf":"sccp_o_146.pdf","row_type":"noael_study","study_id":"sccp_o_146_noael_003"}
SCCS Opinion NOAEL =75 mg/kg/day - oral developmental developmental toxicity {"citation":"Ref.: 18","dose":"Foetal parameters No gross external, soft tissue or skeletal alterations (malformations or variations) were caused by doses as high as 250 mg/kg/day.","effect":"roken incisors. Foetal parameters No gross external, soft tissue or skeletal alterations (malformations or variations) were caused by doses as high as 250 mg/kg/day. There were no dosage-dependent, significant differences in the litter or foetal incidences of any gross external, soft tissue or skeletal alterations. Ossification site averages were comparable among the groups and no biologically important differences occurred. Conclusions On the basis of these data, the maternal no-observable-adverse-effect-level (NOAEL) for HC Orange n° 1 (GTS03977) is 75 mg/kg/day (the 250 mg/kg/day dosage produced clinical signs of rales and decreases in body weight, body weight gain and absolute feed consumption). The developmental NOAEL of GTS03977 is 250 mg/kg/day (no effects were observed at the highest dose tested). Ref.: 18","page":26,"pdf":"sccp_o_146.pdf","row_type":"noael_study","study_id":"sccp_o_146_noael_004"}
SCCS Opinion NOAEL =250 mg/kg/day - oral developmental developmental toxicity {"citation":"Ref.: 18","dose":"Conclusions On the basis of these data, the maternal no-observable-adverse-effect-level (NOAEL) for HC Orange n° 1 (GTS03977) is 75 mg/kg/day (the 250 mg/kg/day dosage produced clinical signs of rales and decreases in body weight, body weight gain and absolute feed consumption).","effect":"t differences in the litter or foetal incidences of any gross external, soft tissue or skeletal alterations. Ossification site averages were comparable among the groups and no biologically important differences occurred. Conclusions On the basis of these data, the maternal no-observable-adverse-effect-level (NOAEL) for HC Orange n° 1 (GTS03977) is 75 mg/kg/day (the 250 mg/kg/day dosage produced clinical signs of rales and decreases in body weight, body weight gain and absolute feed consumption). The developmental NOAEL of GTS03977 is 250 mg/kg/day (no effects were observed at the highest dose tested). Ref.: 18","page":26,"pdf":"sccp_o_146.pdf","row_type":"noael_study","study_id":"sccp_o_146_noael_005"}
SCCS Opinion NOAEL =0.15 % rat dermal 13 week developmental toxicity {"citation":"Ref.: 19 Comment This study indicates that HC Orange No1 in this hair dye formulation is not teratogenic","dose":"There were no significant differences in body weight gain or food consumption in treated animals versus the negative control groups The number of corpora lutea, implantations, resorptions and abortions were similar to the negative controls.","effect":"ed. No signs of irritation were noted. No signs of toxicity were seen throughout the study. There were no significant differences in body weight gain or food consumption in treated animals versus the negative control groups The number of corpora lutea, implantations, resorptions and abortions were similar to the negative controls. Foetal parameters: The sex ratio and number of live foetuses, dead or resorbed foetuses resorptions and foetal abnormalities were similar to the negative controls. A maternal and foetal NOAEL in this hair dye formulation was derived of 0.15% HC Orange #1. Ref.: 19 Comment This study indicates that HC Orange No1 in this hair dye formulation is not teratogenic. Included in this publication was a 13 week topical application study on New Zealand white rabbit that suggested that the use of this hair dye formulation twice a week, at the same concentrations as in the above rat study, had no toxic effect. 3.3.9. Toxicokinetics No data submitted 3.3.10. Photo-induced toxicity No data submitted 3.3.11. Hum","page":27,"pdf":"sccp_o_146.pdf","row_type":"noael_study","study_id":"sccp_o_146_noael_006"}
SCCS Opinion NOAEL =0.024 mg/kg bw rat oral 90-day dermal absorption {"dose":"Safety evaluation (including calculation of the MoS) CALCULATION OF THE MARGIN OF SAFETY (HC Orange n° 1) (Non-oxidative / semi-permanent) Maximum absorption through the skin A (μg/cm2) = 2.06 µg/cm² Skin Area surface SAS (cm2) = 700 cm2 Dermal absorption per treatment SAS x A x 0.001 = 1.442 mg Typical body weight of human = 60 kg Systemic expo...","effect":"SCCP/1164/08 Opinion on HC Orange n° 1 28 3.3.13. Safety evaluation (including calculation of the MoS) CALCULATION OF THE MARGIN OF SAFETY (HC Orange n° 1) (Non-oxidative / semi-permanent) Maximum absorption through the skin A (μg/cm2) = 2.06 µg/cm² Skin Area surface SAS (cm2) = 700 cm2 Dermal absorption per treatment SAS x A x 0.001 = 1.442 mg Typical body weight of human = 60 kg Systemic exposure dose (SED) SAS x A x 0.001/60 = 0.024 mg/kg bw No observed adverse effect level NOAEL = 25 mg/kg bw (90-day, oral, rat) Margin of Safety NOAEL / SED = 1042 3.3.14. Discussion Physico-chemical properties HC Orange n° 1 is used as an ingredient in non-oxidative hair dye formulations at levels up to 1%. The stability of HC Orange n° 1 in marketed products is not described. Only one batch of HC Orange n° 1 has been analyzed and characterized. Calculated values of Log Pow cannot be accepted as an estimate of the true physical constant without justification. The absolute content of the dye in a","page":28,"pdf":"sccp_o_146.pdf","row_type":"noael_study","study_id":"sccp_o_146_noael_007"}
SCCS Opinion NOAEL =25 mg/kg bw rat oral 90-day dermal absorption {"dose":"Safety evaluation (including calculation of the MoS) CALCULATION OF THE MARGIN OF SAFETY (HC Orange n° 1) (Non-oxidative / semi-permanent) Maximum absorption through the skin A (μg/cm2) = 2.06 µg/cm² Skin Area surface SAS (cm2) = 700 cm2 Dermal absorption per treatment SAS x A x 0.001 = 1.442 mg Typical body weight of human = 60 kg Systemic expo...","effect":"SCCP/1164/08 Opinion on HC Orange n° 1 28 3.3.13. Safety evaluation (including calculation of the MoS) CALCULATION OF THE MARGIN OF SAFETY (HC Orange n° 1) (Non-oxidative / semi-permanent) Maximum absorption through the skin A (μg/cm2) = 2.06 µg/cm² Skin Area surface SAS (cm2) = 700 cm2 Dermal absorption per treatment SAS x A x 0.001 = 1.442 mg Typical body weight of human = 60 kg Systemic exposure dose (SED) SAS x A x 0.001/60 = 0.024 mg/kg bw No observed adverse effect level NOAEL = 25 mg/kg bw (90-day, oral, rat) Margin of Safety NOAEL / SED = 1042 3.3.14. Discussion Physico-chemical properties HC Orange n° 1 is used as an ingredient in non-oxidative hair dye formulations at levels up to 1%. The stability of HC Orange n° 1 in marketed products is not described. Only one batch of HC Orange n° 1 has been analyzed and characterized. Calculated values of Log Pow cannot be accepted as an estimate of the true physical constant without justification. The absolute content of the dye in any of","page":28,"pdf":"sccp_o_146.pdf","row_type":"noael_study","study_id":"sccp_o_146_noael_008"}
SCCS Opinion NOAEL =75 mg/kg bw/day guinea pig - developmental reproductive toxicity {"dose":"General toxicity The no-observable-adverse-effect-level (NOAEL) for HC Orange n° 1 was determined to be 25 mg/kg bw/d in the 90 study.","effect":"levels up to 1%. The stability of HC Orange n° 1 in marketed products is not described. Only one batch of HC Orange n° 1 has been analyzed and characterized. Calculated values of Log Pow cannot be accepted as an estimate of the true physical constant without justification. The absolute content of the dye in any of the batches used is not reported. General toxicity The no-observable-adverse-effect-level (NOAEL) for HC Orange n° 1 was determined to be 25 mg/kg bw/d in the 90 study. In the reproductive studies, the NOAEL for maternal toxicity was 75 mg/kg bw/day and 250 mg/kg bw/day for developmental toxicity. Irritation / sensitisation Under the test conditions, HC Orange n° 1 was not a skin irritant. HC Orange n° 1 is considered to have the potential to produce transient mild eye irritation. No evidence of sensitisation was observed in a Guinea Pig Maximisation Test. It did not induce a hypersensitivity response in an LLNA. However, as the tested concentrations were too low, a skin sensitising potential cannot be excluded. D","page":28,"pdf":"sccp_o_146.pdf","row_type":"noael_study","study_id":"sccp_o_146_noael_011"}
SCCS Opinion NOAEL =750 mg/kg/day rat oral Sub-chronic repeated dose toxicity {"citation":"Ref.: 10 Comment This was a range-finding study","dose":"These increases were considered dose related and possibly adverse.","effect":"The increases in liver- and kidney-to-body weight percentages were statistically significant. These increases were considered dose related and possibly adverse. There were no dose-related macroscopic observations. The toxicological significance of clinical pathological changes at mid-high and high doses could not be determined since though the tissues were preserved, no histopathology was performed. Based on relative changes in liver and kidney weights and related clinical pathology findings at 750 mg/kg/day, the NOAEL following oral gavage of GTS03977 was considered to be 300 mg/kg/day. Ref.: 10 Comment This was a range-finding study. The NOAEL of 300 mg/kg/day was derived without assessing the histopathology. 3.3.5.2. Sub-chronic (90 days) oral / dermal / inhalation toxicity Guideline: OECD 408 (1998) Species/strain: Rat, Sprague Dawley Crl:CD IGS BR Group size: 5 per dose/sex; 50 in total Test substance: GTS03977 Batch: # 32 Purity: 100.3% Dose: 0, 2.5, 10, 25 mg/kg bw/day Route: oral gavage Volume/Vehicle: 5 mL/kg in poly","page":15,"pdf":"sccp_o_146.pdf","row_type":"noael_study","study_id":"sccp_o_146_noael_001"}
SCCS Opinion NOAEL =300 mg/kg/day rat oral Sub-chronic repeated dose toxicity {"citation":"Ref.: 10 Comment This was a range-finding study","dose":"There were no dose-related macroscopic observations.","effect":"related and possibly adverse. There were no dose-related macroscopic observations. The toxicological significance of clinical pathological changes at mid-high and high doses could not be determined since though the tissues were preserved, no histopathology was performed. Based on relative changes in liver and kidney weights and related clinical pathology findings at 750 mg/kg/day, the NOAEL following oral gavage of GTS03977 was considered to be 300 mg/kg/day. Ref.: 10 Comment This was a range-finding study. The NOAEL of 300 mg/kg/day was derived without assessing the histopathology. 3.3.5.2. Sub-chronic (90 days) oral / dermal / inhalation toxicity Guideline: OECD 408 (1998) Species/strain: Rat, Sprague Dawley Crl:CD IGS BR Group size: 5 per dose/sex; 50 in total Test substance: GTS03977 Batch: # 32 Purity: 100.3% Dose: 0, 2.5, 10, 25 mg/kg bw/day Route: oral gavage Volume/Vehicle: 5 mL/kg in polyethylene glycol 400 Exposure: 91 days Recovery period: 4 weeks GLP: in compliance Date: 13.09.2005 The animals were observed twic","page":15,"pdf":"sccp_o_146.pdf","row_type":"noael_study","study_id":"sccp_o_146_noael_002"}
SCCS Opinion NOAEL =25 mg/kg bw/d - - Chronic carcinogenicity {"citation":"Ref.: 11 Comment According the OECD guidelines, the highest dose should induce toxicity","dose":"There was a dose-related increase in the incidence of orange staining of fur and skin in animals dosed at 10 or 25 mg/kg/day.","effect":"mean body weights, body weight changes, or food consumption were observed. There was a dose-related increase in the incidence of orange staining of fur and skin in animals dosed at 10 or 25 mg/kg/day. Urine was darker or discoloured for males at all dose levels and females given 10 or 25 mg/kg/day. No other clear effects on clinical pathology test were recorded. Conclusion There were no other statistically significant treatment-related effects in any dose group at the end of the treatment and recovery phases. The NOAEL for GTS03977was determined to be 25 mg/kg bw/d in this study. Ref.: 11 Comment According the OECD guidelines, the highest dose should induce toxicity. 3.3.5.3. Chronic (> 12 months) toxicity See 3.3.7. Carcinogenicity 3.3.6. Mutagenicity / Genotoxicity 3.3.6.1 Mutagenicity / Genotoxicity in vitro Bacterial Reverse Mutation Test Guideline: OECD 471 Species/strain: Salmonella typhimurium TA98, TA100, TA1535, TA1537 and Escherichia coli WP2uvrA (pKM101) Replicates: duplicates or triplicates in 2 individual exp","page":16,"pdf":"sccp_o_146.pdf","row_type":"noael_study","study_id":"sccp_o_146_noael_003"}
SCCS Opinion NOAEL =75 mg/kg/day - oral developmental developmental toxicity {"citation":"Ref.: 18","dose":"Foetal parameters No gross external, soft tissue or skeletal alterations (malformations or variations) were caused by doses as high as 250 mg/kg/day.","effect":"roken incisors. Foetal parameters No gross external, soft tissue or skeletal alterations (malformations or variations) were caused by doses as high as 250 mg/kg/day. There were no dosage-dependent, significant differences in the litter or foetal incidences of any gross external, soft tissue or skeletal alterations. Ossification site averages were comparable among the groups and no biologically important differences occurred. Conclusions On the basis of these data, the maternal no-observable-adverse-effect-level (NOAEL) for HC Orange n° 1 (GTS03977) is 75 mg/kg/day (the 250 mg/kg/day dosage produced clinical signs of rales and decreases in body weight, body weight gain and absolute feed consumption). The developmental NOAEL of GTS03977 is 250 mg/kg/day (no effects were observed at the highest dose tested). Ref.: 18","page":26,"pdf":"sccp_o_146.pdf","row_type":"noael_study","study_id":"sccp_o_146_noael_004"}
SCCS Opinion NOAEL =250 mg/kg/day - oral developmental developmental toxicity {"citation":"Ref.: 18","dose":"Conclusions On the basis of these data, the maternal no-observable-adverse-effect-level (NOAEL) for HC Orange n° 1 (GTS03977) is 75 mg/kg/day (the 250 mg/kg/day dosage produced clinical signs of rales and decreases in body weight, body weight gain and absolute feed consumption).","effect":"t differences in the litter or foetal incidences of any gross external, soft tissue or skeletal alterations. Ossification site averages were comparable among the groups and no biologically important differences occurred. Conclusions On the basis of these data, the maternal no-observable-adverse-effect-level (NOAEL) for HC Orange n° 1 (GTS03977) is 75 mg/kg/day (the 250 mg/kg/day dosage produced clinical signs of rales and decreases in body weight, body weight gain and absolute feed consumption). The developmental NOAEL of GTS03977 is 250 mg/kg/day (no effects were observed at the highest dose tested). Ref.: 18","page":26,"pdf":"sccp_o_146.pdf","row_type":"noael_study","study_id":"sccp_o_146_noael_005"}
SCCS Opinion NOAEL =0.15 % rat dermal 13 week developmental toxicity {"citation":"Ref.: 19 Comment This study indicates that HC Orange No1 in this hair dye formulation is not teratogenic","dose":"There were no significant differences in body weight gain or food consumption in treated animals versus the negative control groups The number of corpora lutea, implantations, resorptions and abortions were similar to the negative controls.","effect":"ed. No signs of irritation were noted. No signs of toxicity were seen throughout the study. There were no significant differences in body weight gain or food consumption in treated animals versus the negative control groups The number of corpora lutea, implantations, resorptions and abortions were similar to the negative controls. Foetal parameters: The sex ratio and number of live foetuses, dead or resorbed foetuses resorptions and foetal abnormalities were similar to the negative controls. A maternal and foetal NOAEL in this hair dye formulation was derived of 0.15% HC Orange #1. Ref.: 19 Comment This study indicates that HC Orange No1 in this hair dye formulation is not teratogenic. Included in this publication was a 13 week topical application study on New Zealand white rabbit that suggested that the use of this hair dye formulation twice a week, at the same concentrations as in the above rat study, had no toxic effect. 3.3.9. Toxicokinetics No data submitted 3.3.10. Photo-induced toxicity No data submitted 3.3.11. Hum","page":27,"pdf":"sccp_o_146.pdf","row_type":"noael_study","study_id":"sccp_o_146_noael_006"}
SCCS Opinion NOAEL =0.024 mg/kg bw rat oral 90-day dermal absorption {"dose":"Safety evaluation (including calculation of the MoS) CALCULATION OF THE MARGIN OF SAFETY (HC Orange n° 1) (Non-oxidative / semi-permanent) Maximum absorption through the skin A (μg/cm2) = 2.06 µg/cm² Skin Area surface SAS (cm2) = 700 cm2 Dermal absorption per treatment SAS x A x 0.001 = 1.442 mg Typical body weight of human = 60 kg Systemic expo...","effect":"SCCP/1164/08 Opinion on HC Orange n° 1 28 3.3.13. Safety evaluation (including calculation of the MoS) CALCULATION OF THE MARGIN OF SAFETY (HC Orange n° 1) (Non-oxidative / semi-permanent) Maximum absorption through the skin A (μg/cm2) = 2.06 µg/cm² Skin Area surface SAS (cm2) = 700 cm2 Dermal absorption per treatment SAS x A x 0.001 = 1.442 mg Typical body weight of human = 60 kg Systemic exposure dose (SED) SAS x A x 0.001/60 = 0.024 mg/kg bw No observed adverse effect level NOAEL = 25 mg/kg bw (90-day, oral, rat) Margin of Safety NOAEL / SED = 1042 3.3.14. Discussion Physico-chemical properties HC Orange n° 1 is used as an ingredient in non-oxidative hair dye formulations at levels up to 1%. The stability of HC Orange n° 1 in marketed products is not described. Only one batch of HC Orange n° 1 has been analyzed and characterized. Calculated values of Log Pow cannot be accepted as an estimate of the true physical constant without justification. The absolute content of the dye in a","page":28,"pdf":"sccp_o_146.pdf","row_type":"noael_study","study_id":"sccp_o_146_noael_007"}
SCCS Opinion NOAEL =25 mg/kg bw rat oral 90-day dermal absorption {"dose":"Safety evaluation (including calculation of the MoS) CALCULATION OF THE MARGIN OF SAFETY (HC Orange n° 1) (Non-oxidative / semi-permanent) Maximum absorption through the skin A (μg/cm2) = 2.06 µg/cm² Skin Area surface SAS (cm2) = 700 cm2 Dermal absorption per treatment SAS x A x 0.001 = 1.442 mg Typical body weight of human = 60 kg Systemic expo...","effect":"SCCP/1164/08 Opinion on HC Orange n° 1 28 3.3.13. Safety evaluation (including calculation of the MoS) CALCULATION OF THE MARGIN OF SAFETY (HC Orange n° 1) (Non-oxidative / semi-permanent) Maximum absorption through the skin A (μg/cm2) = 2.06 µg/cm² Skin Area surface SAS (cm2) = 700 cm2 Dermal absorption per treatment SAS x A x 0.001 = 1.442 mg Typical body weight of human = 60 kg Systemic exposure dose (SED) SAS x A x 0.001/60 = 0.024 mg/kg bw No observed adverse effect level NOAEL = 25 mg/kg bw (90-day, oral, rat) Margin of Safety NOAEL / SED = 1042 3.3.14. Discussion Physico-chemical properties HC Orange n° 1 is used as an ingredient in non-oxidative hair dye formulations at levels up to 1%. The stability of HC Orange n° 1 in marketed products is not described. Only one batch of HC Orange n° 1 has been analyzed and characterized. Calculated values of Log Pow cannot be accepted as an estimate of the true physical constant without justification. The absolute content of the dye in any of","page":28,"pdf":"sccp_o_146.pdf","row_type":"noael_study","study_id":"sccp_o_146_noael_008"}
SCCS Opinion NOAEL =75 mg/kg bw/day guinea pig - developmental reproductive toxicity {"dose":"General toxicity The no-observable-adverse-effect-level (NOAEL) for HC Orange n° 1 was determined to be 25 mg/kg bw/d in the 90 study.","effect":"levels up to 1%. The stability of HC Orange n° 1 in marketed products is not described. Only one batch of HC Orange n° 1 has been analyzed and characterized. Calculated values of Log Pow cannot be accepted as an estimate of the true physical constant without justification. The absolute content of the dye in any of the batches used is not reported. General toxicity The no-observable-adverse-effect-level (NOAEL) for HC Orange n° 1 was determined to be 25 mg/kg bw/d in the 90 study. In the reproductive studies, the NOAEL for maternal toxicity was 75 mg/kg bw/day and 250 mg/kg bw/day for developmental toxicity. Irritation / sensitisation Under the test conditions, HC Orange n° 1 was not a skin irritant. HC Orange n° 1 is considered to have the potential to produce transient mild eye irritation. No evidence of sensitisation was observed in a Guinea Pig Maximisation Test. It did not induce a hypersensitivity response in an LLNA. However, as the tested concentrations were too low, a skin sensitising potential cannot be excluded. D","page":28,"pdf":"sccp_o_146.pdf","row_type":"noael_study","study_id":"sccp_o_146_noael_011"}
Regulatory source 11 endpoints
Source Endpoint Type Value Unit Species Route Duration Study Type Reference
Regulatory source carcinogenicity 25 mg/kg bw/d - - Chronic carcinogenicity SOURCE_SUBDIR=sccp_o_146; REPORT_TITLE=OPINION ON HC Orange n° 1 COLIPA n° B47; OPINION_NUMBER=SCCP/1164/08; COMMITTEE=Scientific Committee on Consumer Products (SCCP); REPORT_DATE=30 September 2008; VALUE_TEXT=25; DOSE=There was a dose-related increase in the incidence of orange staining of fur and skin in animals dosed at 10 or 25 mg/kg/day.; EFFECT=mean body weights, body weight changes, or food consumption were observed. There was a dose-related increase in the incidence of orange staining of fur and skin in animals dosed at 10 or 25 mg/kg/day. Urine was darker or discoloured for males at all dose levels and females given 10 or 25 mg/kg/day. No other clear effects on clinical pathology test were recorded. Conclusion There were no other statistically significant treatment-related effects in any dose group at the end of the treatment and recovery phases. The NOAEL for GTS03977was determined to be 25 mg/kg bw/d in this study. Ref.: 11 Comment According the OECD guidelines, the highest dose should induce toxicity. 3.3.5.3. Chronic (> 12 months) toxicity See 3.3.7. Carcinogenicity 3.3.6. Mutagenicity / Genotoxicity 3.3.6.1 Mutagenicity / Genotoxicity in vitro Bacterial Reverse Mutation Test Guideline: OECD 471 Species/strain: Salmonella typhimurium TA98, TA100, TA1535, TA1537 and Escherichia coli WP2uvrA (pKM101) Replicates: duplicates or triplicates in 2 individual exp; CITATION=Ref.: 11 Comment According the OECD guidelines, the highest dose should induce toxicity; CITATION_NUMBERS=[11]; REFERENCE=Ref.: 11 Comment According the OECD guidelines, the highest dose should induce toxicity; DETAILS_JSON={"cas_number":"54381-08-7","citation":"Ref.: 11 Comment According the OECD guidelines, the highest dose should induce toxicity","dose":"There was a dose-related increase in the incidence of orange staining of fur and skin in animals dosed at 10 or 25 mg/kg/day.","duration":"Chronic","effect":"mean body weights, body weight changes, or food consumption were observed. There was a dose-related increase in the incidence of orange staining of fur and skin in animals dosed at 10 or 25 mg/kg/day. Urine was darker or discoloured for males at all dose levels and females given 10 or 25 mg/kg/day. No other clear effects on clinical pathology test were recorded. Conclusion There were no other statistically significant treatment-related effects in any dose group at the end of the treatment and recovery phases. The NOAEL for GTS03977was determined to be 25 mg/kg bw/d in this study. Ref.: 11 Comment According the OECD guidelines, the highest dose should induce toxicity. 3.3.5.3. Chronic (> 12 months) toxicity See 3.3.7. Carcinogenicity 3.3.6. Mutagenicity / Genotoxicity 3.3.6.1 Mutagenicity / Genotoxicity in vitro Bacterial Reverse Mutation Test Guideline: OECD 471 Species/strain: Salmonella typhimurium TA98, TA100, TA1535, TA1537 and Escherichia coli WP2uvrA (pKM101) Replicates: duplicates or triplicates in 2 individual exp","endpoint":"carcinogenicity","ingredient":"HC Orange No. 1","loael_value":"","noael_unit":"mg/kg bw/d","noael_value":"25","page":16,"route":"","species":"","study_id":"sccp_o_146_noael_003"}
Regulatory source dermal absorption =0.024 mg/kg bw rat oral 90-day dermal absorption SOURCE_SUBDIR=sccp_o_146; REPORT_TITLE=OPINION ON HC Orange n° 1 COLIPA n° B47; OPINION_NUMBER=SCCP/1164/08; COMMITTEE=Scientific Committee on Consumer Products (SCCP); REPORT_DATE=30 September 2008; VALUE_TEXT== 0.024; DOSE=Safety evaluation (including calculation of the MoS) CALCULATION OF THE MARGIN OF SAFETY (HC Orange n° 1) (Non-oxidative / semi-permanent) Maximum absorption through the skin A (μg/cm2) = 2.06 µg/cm² Skin Area surface SAS (cm2) = 700 cm2 Dermal absorption per treatment SAS x A x 0.001 = 1.442 mg Typical body weight of human = 60 kg Systemic expo...; EFFECT=SCCP/1164/08 Opinion on HC Orange n° 1 28 3.3.13. Safety evaluation (including calculation of the MoS) CALCULATION OF THE MARGIN OF SAFETY (HC Orange n° 1) (Non-oxidative / semi-permanent) Maximum absorption through the skin A (μg/cm2) = 2.06 µg/cm² Skin Area surface SAS (cm2) = 700 cm2 Dermal absorption per treatment SAS x A x 0.001 = 1.442 mg Typical body weight of human = 60 kg Systemic exposure dose (SED) SAS x A x 0.001/60 = 0.024 mg/kg bw No observed adverse effect level NOAEL = 25 mg/kg bw (90-day, oral, rat) Margin of Safety NOAEL / SED = 1042 3.3.14. Discussion Physico-chemical properties HC Orange n° 1 is used as an ingredient in non-oxidative hair dye formulations at levels up to 1%. The stability of HC Orange n° 1 in marketed products is not described. Only one batch of HC Orange n° 1 has been analyzed and characterized. Calculated values of Log Pow cannot be accepted as an estimate of the true physical constant without justification. The absolute content of the dye in a; CITATION_NUMBERS=[]; DETAILS_JSON={"cas_number":"54381-08-7","citation":"","dose":"Safety evaluation (including calculation of the MoS) CALCULATION OF THE MARGIN OF SAFETY (HC Orange n° 1) (Non-oxidative / semi-permanent) Maximum absorption through the skin A (μg/cm2) = 2.06 µg/cm² Skin Area surface SAS (cm2) = 700 cm2 Dermal absorption per treatment SAS x A x 0.001 = 1.442 mg Typical body weight of human = 60 kg Systemic expo...","duration":"90-day","effect":"SCCP/1164/08 Opinion on HC Orange n° 1 28 3.3.13. Safety evaluation (including calculation of the MoS) CALCULATION OF THE MARGIN OF SAFETY (HC Orange n° 1) (Non-oxidative / semi-permanent) Maximum absorption through the skin A (μg/cm2) = 2.06 µg/cm² Skin Area surface SAS (cm2) = 700 cm2 Dermal absorption per treatment SAS x A x 0.001 = 1.442 mg Typical body weight of human = 60 kg Systemic exposure dose (SED) SAS x A x 0.001/60 = 0.024 mg/kg bw No observed adverse effect level NOAEL = 25 mg/kg bw (90-day, oral, rat) Margin of Safety NOAEL / SED = 1042 3.3.14. Discussion Physico-chemical properties HC Orange n° 1 is used as an ingredient in non-oxidative hair dye formulations at levels up to 1%. The stability of HC Orange n° 1 in marketed products is not described. Only one batch of HC Orange n° 1 has been analyzed and characterized. Calculated values of Log Pow cannot be accepted as an estimate of the true physical constant without justification. The absolute content of the dye in a","endpoint":"dermal absorption","ingredient":"HC Orange No. 1","loael_value":"","noael_unit":"mg/kg bw","noael_value":"= 0.024","page":28,"route":"oral","species":"rat","study_id":"sccp_o_146_noael_007"}
Regulatory source dermal absorption =25 mg/kg bw rat oral 90-day dermal absorption SOURCE_SUBDIR=sccp_o_146; REPORT_TITLE=OPINION ON HC Orange n° 1 COLIPA n° B47; OPINION_NUMBER=SCCP/1164/08; COMMITTEE=Scientific Committee on Consumer Products (SCCP); REPORT_DATE=30 September 2008; VALUE_TEXT== 25; DOSE=Safety evaluation (including calculation of the MoS) CALCULATION OF THE MARGIN OF SAFETY (HC Orange n° 1) (Non-oxidative / semi-permanent) Maximum absorption through the skin A (μg/cm2) = 2.06 µg/cm² Skin Area surface SAS (cm2) = 700 cm2 Dermal absorption per treatment SAS x A x 0.001 = 1.442 mg Typical body weight of human = 60 kg Systemic expo...; EFFECT=SCCP/1164/08 Opinion on HC Orange n° 1 28 3.3.13. Safety evaluation (including calculation of the MoS) CALCULATION OF THE MARGIN OF SAFETY (HC Orange n° 1) (Non-oxidative / semi-permanent) Maximum absorption through the skin A (μg/cm2) = 2.06 µg/cm² Skin Area surface SAS (cm2) = 700 cm2 Dermal absorption per treatment SAS x A x 0.001 = 1.442 mg Typical body weight of human = 60 kg Systemic exposure dose (SED) SAS x A x 0.001/60 = 0.024 mg/kg bw No observed adverse effect level NOAEL = 25 mg/kg bw (90-day, oral, rat) Margin of Safety NOAEL / SED = 1042 3.3.14. Discussion Physico-chemical properties HC Orange n° 1 is used as an ingredient in non-oxidative hair dye formulations at levels up to 1%. The stability of HC Orange n° 1 in marketed products is not described. Only one batch of HC Orange n° 1 has been analyzed and characterized. Calculated values of Log Pow cannot be accepted as an estimate of the true physical constant without justification. The absolute content of the dye in any of; CITATION_NUMBERS=[]; DETAILS_JSON={"cas_number":"54381-08-7","citation":"","dose":"Safety evaluation (including calculation of the MoS) CALCULATION OF THE MARGIN OF SAFETY (HC Orange n° 1) (Non-oxidative / semi-permanent) Maximum absorption through the skin A (μg/cm2) = 2.06 µg/cm² Skin Area surface SAS (cm2) = 700 cm2 Dermal absorption per treatment SAS x A x 0.001 = 1.442 mg Typical body weight of human = 60 kg Systemic expo...","duration":"90-day","effect":"SCCP/1164/08 Opinion on HC Orange n° 1 28 3.3.13. Safety evaluation (including calculation of the MoS) CALCULATION OF THE MARGIN OF SAFETY (HC Orange n° 1) (Non-oxidative / semi-permanent) Maximum absorption through the skin A (μg/cm2) = 2.06 µg/cm² Skin Area surface SAS (cm2) = 700 cm2 Dermal absorption per treatment SAS x A x 0.001 = 1.442 mg Typical body weight of human = 60 kg Systemic exposure dose (SED) SAS x A x 0.001/60 = 0.024 mg/kg bw No observed adverse effect level NOAEL = 25 mg/kg bw (90-day, oral, rat) Margin of Safety NOAEL / SED = 1042 3.3.14. Discussion Physico-chemical properties HC Orange n° 1 is used as an ingredient in non-oxidative hair dye formulations at levels up to 1%. The stability of HC Orange n° 1 in marketed products is not described. Only one batch of HC Orange n° 1 has been analyzed and characterized. Calculated values of Log Pow cannot be accepted as an estimate of the true physical constant without justification. The absolute content of the dye in any of","endpoint":"dermal absorption","ingredient":"HC Orange No. 1","loael_value":"","noael_unit":"mg/kg bw","noael_value":"= 25","page":28,"route":"oral","species":"rat","study_id":"sccp_o_146_noael_008"}
Regulatory source dermal absorption =25 mg/kg bw rat oral 90-day dermal absorption SOURCE_SUBDIR=sccp_o_146; REPORT_TITLE=OPINION ON HC Orange n° 1 COLIPA n° B47; OPINION_NUMBER=SCCP/1164/08; COMMITTEE=Scientific Committee on Consumer Products (SCCP); REPORT_DATE=30 September 2008; VALUE_TEXT== 25; DOSE=Safety evaluation (including calculation of the MoS) CALCULATION OF THE MARGIN OF SAFETY (HC Orange n° 1) (Non-oxidative / semi-permanent) Maximum absorption through the skin A (μg/cm2) = 2.06 µg/cm² Skin Area surface SAS (cm2) = 700 cm2 Dermal absorption per treatment SAS x A x 0.001 = 1.442 mg Typical body weight of human = 60 kg Systemic expo...; EFFECT=Orange n° 1 28 3.3.13. Safety evaluation (including calculation of the MoS) CALCULATION OF THE MARGIN OF SAFETY (HC Orange n° 1) (Non-oxidative / semi-permanent) Maximum absorption through the skin A (μg/cm2) = 2.06 µg/cm² Skin Area surface SAS (cm2) = 700 cm2 Dermal absorption per treatment SAS x A x 0.001 = 1.442 mg Typical body weight of human = 60 kg Systemic exposure dose (SED) SAS x A x 0.001/60 = 0.024 mg/kg bw No observed adverse effect level NOAEL = 25 mg/kg bw (90-day, oral, rat) Margin of Safety NOAEL / SED = 1042 3.3.14. Discussion Physico-chemical properties HC Orange n° 1 is used as an ingredient in non-oxidative hair dye formulations at levels up to 1%. The stability of HC Orange n° 1 in marketed products is not described. Only one batch of HC Orange n° 1 has been analyzed and characterized. Calculated values of Log Pow cannot be accepted as an estimate of the true physical constant without justification. The absolute content of the dye in any of the batches used is not reported. General toxicity The n; CITATION_NUMBERS=[]; DETAILS_JSON={"cas_number":"54381-08-7","citation":"","dose":"Safety evaluation (including calculation of the MoS) CALCULATION OF THE MARGIN OF SAFETY (HC Orange n° 1) (Non-oxidative / semi-permanent) Maximum absorption through the skin A (μg/cm2) = 2.06 µg/cm² Skin Area surface SAS (cm2) = 700 cm2 Dermal absorption per treatment SAS x A x 0.001 = 1.442 mg Typical body weight of human = 60 kg Systemic expo...","duration":"90-day","effect":"Orange n° 1 28 3.3.13. Safety evaluation (including calculation of the MoS) CALCULATION OF THE MARGIN OF SAFETY (HC Orange n° 1) (Non-oxidative / semi-permanent) Maximum absorption through the skin A (μg/cm2) = 2.06 µg/cm² Skin Area surface SAS (cm2) = 700 cm2 Dermal absorption per treatment SAS x A x 0.001 = 1.442 mg Typical body weight of human = 60 kg Systemic exposure dose (SED) SAS x A x 0.001/60 = 0.024 mg/kg bw No observed adverse effect level NOAEL = 25 mg/kg bw (90-day, oral, rat) Margin of Safety NOAEL / SED = 1042 3.3.14. Discussion Physico-chemical properties HC Orange n° 1 is used as an ingredient in non-oxidative hair dye formulations at levels up to 1%. The stability of HC Orange n° 1 in marketed products is not described. Only one batch of HC Orange n° 1 has been analyzed and characterized. Calculated values of Log Pow cannot be accepted as an estimate of the true physical constant without justification. The absolute content of the dye in any of the batches used is not reported. General toxicity The n","endpoint":"dermal absorption","ingredient":"HC Orange No. 1","loael_value":"","noael_unit":"mg/kg bw","noael_value":"= 25","page":28,"route":"oral","species":"rat","study_id":"sccp_o_146_noael_009"}
Regulatory source developmental toxicity 75 mg/kg/day - oral developmental developmental toxicity SOURCE_SUBDIR=sccp_o_146; REPORT_TITLE=OPINION ON HC Orange n° 1 COLIPA n° B47; OPINION_NUMBER=SCCP/1164/08; COMMITTEE=Scientific Committee on Consumer Products (SCCP); REPORT_DATE=30 September 2008; VALUE_TEXT=75; DOSE=Foetal parameters No gross external, soft tissue or skeletal alterations (malformations or variations) were caused by doses as high as 250 mg/kg/day.; EFFECT=roken incisors. Foetal parameters No gross external, soft tissue or skeletal alterations (malformations or variations) were caused by doses as high as 250 mg/kg/day. There were no dosage-dependent, significant differences in the litter or foetal incidences of any gross external, soft tissue or skeletal alterations. Ossification site averages were comparable among the groups and no biologically important differences occurred. Conclusions On the basis of these data, the maternal no-observable-adverse-effect-level (NOAEL) for HC Orange n° 1 (GTS03977) is 75 mg/kg/day (the 250 mg/kg/day dosage produced clinical signs of rales and decreases in body weight, body weight gain and absolute feed consumption). The developmental NOAEL of GTS03977 is 250 mg/kg/day (no effects were observed at the highest dose tested). Ref.: 18; CITATION=Ref.: 18; CITATION_NUMBERS=[18]; REFERENCE=Ref.: 18; DETAILS_JSON={"cas_number":"54381-08-7","citation":"Ref.: 18","dose":"Foetal parameters No gross external, soft tissue or skeletal alterations (malformations or variations) were caused by doses as high as 250 mg/kg/day.","duration":"developmental","effect":"roken incisors. Foetal parameters No gross external, soft tissue or skeletal alterations (malformations or variations) were caused by doses as high as 250 mg/kg/day. There were no dosage-dependent, significant differences in the litter or foetal incidences of any gross external, soft tissue or skeletal alterations. Ossification site averages were comparable among the groups and no biologically important differences occurred. Conclusions On the basis of these data, the maternal no-observable-adverse-effect-level (NOAEL) for HC Orange n° 1 (GTS03977) is 75 mg/kg/day (the 250 mg/kg/day dosage produced clinical signs of rales and decreases in body weight, body weight gain and absolute feed consumption). The developmental NOAEL of GTS03977 is 250 mg/kg/day (no effects were observed at the highest dose tested). Ref.: 18","endpoint":"developmental toxicity","ingredient":"HC Orange No. 1","loael_value":"","noael_unit":"mg/kg/day","noael_value":"75","page":26,"route":"oral","species":"","study_id":"sccp_o_146_noael_004"}
Regulatory source developmental toxicity 250 mg/kg/day - oral developmental developmental toxicity SOURCE_SUBDIR=sccp_o_146; REPORT_TITLE=OPINION ON HC Orange n° 1 COLIPA n° B47; OPINION_NUMBER=SCCP/1164/08; COMMITTEE=Scientific Committee on Consumer Products (SCCP); REPORT_DATE=30 September 2008; VALUE_TEXT=250; DOSE=Conclusions On the basis of these data, the maternal no-observable-adverse-effect-level (NOAEL) for HC Orange n° 1 (GTS03977) is 75 mg/kg/day (the 250 mg/kg/day dosage produced clinical signs of rales and decreases in body weight, body weight gain and absolute feed consumption).; EFFECT=t differences in the litter or foetal incidences of any gross external, soft tissue or skeletal alterations. Ossification site averages were comparable among the groups and no biologically important differences occurred. Conclusions On the basis of these data, the maternal no-observable-adverse-effect-level (NOAEL) for HC Orange n° 1 (GTS03977) is 75 mg/kg/day (the 250 mg/kg/day dosage produced clinical signs of rales and decreases in body weight, body weight gain and absolute feed consumption). The developmental NOAEL of GTS03977 is 250 mg/kg/day (no effects were observed at the highest dose tested). Ref.: 18; CITATION=Ref.: 18; CITATION_NUMBERS=[18]; REFERENCE=Ref.: 18; DETAILS_JSON={"cas_number":"54381-08-7","citation":"Ref.: 18","dose":"Conclusions On the basis of these data, the maternal no-observable-adverse-effect-level (NOAEL) for HC Orange n° 1 (GTS03977) is 75 mg/kg/day (the 250 mg/kg/day dosage produced clinical signs of rales and decreases in body weight, body weight gain and absolute feed consumption).","duration":"developmental","effect":"t differences in the litter or foetal incidences of any gross external, soft tissue or skeletal alterations. Ossification site averages were comparable among the groups and no biologically important differences occurred. Conclusions On the basis of these data, the maternal no-observable-adverse-effect-level (NOAEL) for HC Orange n° 1 (GTS03977) is 75 mg/kg/day (the 250 mg/kg/day dosage produced clinical signs of rales and decreases in body weight, body weight gain and absolute feed consumption). The developmental NOAEL of GTS03977 is 250 mg/kg/day (no effects were observed at the highest dose tested). Ref.: 18","endpoint":"developmental toxicity","ingredient":"HC Orange No. 1","loael_value":"","noael_unit":"mg/kg/day","noael_value":"250","page":26,"route":"oral","species":"","study_id":"sccp_o_146_noael_005"}
Regulatory source developmental toxicity 0.15 % rat dermal 13 week developmental toxicity SOURCE_SUBDIR=sccp_o_146; REPORT_TITLE=OPINION ON HC Orange n° 1 COLIPA n° B47; OPINION_NUMBER=SCCP/1164/08; COMMITTEE=Scientific Committee on Consumer Products (SCCP); REPORT_DATE=30 September 2008; VALUE_TEXT=0.15; DOSE=There were no significant differences in body weight gain or food consumption in treated animals versus the negative control groups The number of corpora lutea, implantations, resorptions and abortions were similar to the negative controls.; EFFECT=ed. No signs of irritation were noted. No signs of toxicity were seen throughout the study. There were no significant differences in body weight gain or food consumption in treated animals versus the negative control groups The number of corpora lutea, implantations, resorptions and abortions were similar to the negative controls. Foetal parameters: The sex ratio and number of live foetuses, dead or resorbed foetuses resorptions and foetal abnormalities were similar to the negative controls. A maternal and foetal NOAEL in this hair dye formulation was derived of 0.15% HC Orange #1. Ref.: 19 Comment This study indicates that HC Orange No1 in this hair dye formulation is not teratogenic. Included in this publication was a 13 week topical application study on New Zealand white rabbit that suggested that the use of this hair dye formulation twice a week, at the same concentrations as in the above rat study, had no toxic effect. 3.3.9. Toxicokinetics No data submitted 3.3.10. Photo-induced toxicity No data submitted 3.3.11. Hum; CITATION=Ref.: 19 Comment This study indicates that HC Orange No1 in this hair dye formulation is not teratogenic; CITATION_NUMBERS=[19,1]; REFERENCE=Ref.: 19 Comment This study indicates that HC Orange No1 in this hair dye formulation is not teratogenic; DETAILS_JSON={"cas_number":"54381-08-7","citation":"Ref.: 19 Comment This study indicates that HC Orange No1 in this hair dye formulation is not teratogenic","dose":"There were no significant differences in body weight gain or food consumption in treated animals versus the negative control groups The number of corpora lutea, implantations, resorptions and abortions were similar to the negative controls.","duration":"13 week","effect":"ed. No signs of irritation were noted. No signs of toxicity were seen throughout the study. There were no significant differences in body weight gain or food consumption in treated animals versus the negative control groups The number of corpora lutea, implantations, resorptions and abortions were similar to the negative controls. Foetal parameters: The sex ratio and number of live foetuses, dead or resorbed foetuses resorptions and foetal abnormalities were similar to the negative controls. A maternal and foetal NOAEL in this hair dye formulation was derived of 0.15% HC Orange #1. Ref.: 19 Comment This study indicates that HC Orange No1 in this hair dye formulation is not teratogenic. Included in this publication was a 13 week topical application study on New Zealand white rabbit that suggested that the use of this hair dye formulation twice a week, at the same concentrations as in the above rat study, had no toxic effect. 3.3.9. Toxicokinetics No data submitted 3.3.10. Photo-induced toxicity No data submitted 3.3.11. Hum","endpoint":"developmental toxicity","ingredient":"HC Orange No. 1","loael_value":"","noael_unit":"%","noael_value":"0.15","page":27,"route":"dermal","species":"rat","study_id":"sccp_o_146_noael_006"}
Regulatory source repeated dose toxicity 750 mg/kg/day rat oral Sub-chronic repeated dose toxicity SOURCE_SUBDIR=sccp_o_146; REPORT_TITLE=OPINION ON HC Orange n° 1 COLIPA n° B47; OPINION_NUMBER=SCCP/1164/08; COMMITTEE=Scientific Committee on Consumer Products (SCCP); REPORT_DATE=30 September 2008; VALUE_TEXT=750; DOSE=These increases were considered dose related and possibly adverse.; EFFECT=The increases in liver- and kidney-to-body weight percentages were statistically significant. These increases were considered dose related and possibly adverse. There were no dose-related macroscopic observations. The toxicological significance of clinical pathological changes at mid-high and high doses could not be determined since though the tissues were preserved, no histopathology was performed. Based on relative changes in liver and kidney weights and related clinical pathology findings at 750 mg/kg/day, the NOAEL following oral gavage of GTS03977 was considered to be 300 mg/kg/day. Ref.: 10 Comment This was a range-finding study. The NOAEL of 300 mg/kg/day was derived without assessing the histopathology. 3.3.5.2. Sub-chronic (90 days) oral / dermal / inhalation toxicity Guideline: OECD 408 (1998) Species/strain: Rat, Sprague Dawley Crl:CD IGS BR Group size: 5 per dose/sex; 50 in total Test substance: GTS03977 Batch: # 32 Purity: 100.3% Dose: 0, 2.5, 10, 25 mg/kg bw/day Route: oral gavage Volume/Vehicle: 5 mL/kg in poly; CITATION=Ref.: 10 Comment This was a range-finding study; CITATION_NUMBERS=[10]; REFERENCE=Ref.: 10 Comment This was a range-finding study; DETAILS_JSON={"cas_number":"54381-08-7","citation":"Ref.: 10 Comment This was a range-finding study","dose":"These increases were considered dose related and possibly adverse.","duration":"Sub-chronic","effect":"The increases in liver- and kidney-to-body weight percentages were statistically significant. These increases were considered dose related and possibly adverse. There were no dose-related macroscopic observations. The toxicological significance of clinical pathological changes at mid-high and high doses could not be determined since though the tissues were preserved, no histopathology was performed. Based on relative changes in liver and kidney weights and related clinical pathology findings at 750 mg/kg/day, the NOAEL following oral gavage of GTS03977 was considered to be 300 mg/kg/day. Ref.: 10 Comment This was a range-finding study. The NOAEL of 300 mg/kg/day was derived without assessing the histopathology. 3.3.5.2. Sub-chronic (90 days) oral / dermal / inhalation toxicity Guideline: OECD 408 (1998) Species/strain: Rat, Sprague Dawley Crl:CD IGS BR Group size: 5 per dose/sex; 50 in total Test substance: GTS03977 Batch: # 32 Purity: 100.3% Dose: 0, 2.5, 10, 25 mg/kg bw/day Route: oral gavage Volume/Vehicle: 5 mL/kg in poly","endpoint":"repeated dose toxicity","ingredient":"HC Orange No. 1","loael_value":"","noael_unit":"mg/kg/day","noael_value":"750","page":15,"route":"oral","species":"rat","study_id":"sccp_o_146_noael_001"}
Regulatory source repeated dose toxicity 300 mg/kg/day rat oral Sub-chronic repeated dose toxicity SOURCE_SUBDIR=sccp_o_146; REPORT_TITLE=OPINION ON HC Orange n° 1 COLIPA n° B47; OPINION_NUMBER=SCCP/1164/08; COMMITTEE=Scientific Committee on Consumer Products (SCCP); REPORT_DATE=30 September 2008; VALUE_TEXT=300; DOSE=There were no dose-related macroscopic observations.; EFFECT=related and possibly adverse. There were no dose-related macroscopic observations. The toxicological significance of clinical pathological changes at mid-high and high doses could not be determined since though the tissues were preserved, no histopathology was performed. Based on relative changes in liver and kidney weights and related clinical pathology findings at 750 mg/kg/day, the NOAEL following oral gavage of GTS03977 was considered to be 300 mg/kg/day. Ref.: 10 Comment This was a range-finding study. The NOAEL of 300 mg/kg/day was derived without assessing the histopathology. 3.3.5.2. Sub-chronic (90 days) oral / dermal / inhalation toxicity Guideline: OECD 408 (1998) Species/strain: Rat, Sprague Dawley Crl:CD IGS BR Group size: 5 per dose/sex; 50 in total Test substance: GTS03977 Batch: # 32 Purity: 100.3% Dose: 0, 2.5, 10, 25 mg/kg bw/day Route: oral gavage Volume/Vehicle: 5 mL/kg in polyethylene glycol 400 Exposure: 91 days Recovery period: 4 weeks GLP: in compliance Date: 13.09.2005 The animals were observed twic; CITATION=Ref.: 10 Comment This was a range-finding study; CITATION_NUMBERS=[10]; REFERENCE=Ref.: 10 Comment This was a range-finding study; DETAILS_JSON={"cas_number":"54381-08-7","citation":"Ref.: 10 Comment This was a range-finding study","dose":"There were no dose-related macroscopic observations.","duration":"Sub-chronic","effect":"related and possibly adverse. There were no dose-related macroscopic observations. The toxicological significance of clinical pathological changes at mid-high and high doses could not be determined since though the tissues were preserved, no histopathology was performed. Based on relative changes in liver and kidney weights and related clinical pathology findings at 750 mg/kg/day, the NOAEL following oral gavage of GTS03977 was considered to be 300 mg/kg/day. Ref.: 10 Comment This was a range-finding study. The NOAEL of 300 mg/kg/day was derived without assessing the histopathology. 3.3.5.2. Sub-chronic (90 days) oral / dermal / inhalation toxicity Guideline: OECD 408 (1998) Species/strain: Rat, Sprague Dawley Crl:CD IGS BR Group size: 5 per dose/sex; 50 in total Test substance: GTS03977 Batch: # 32 Purity: 100.3% Dose: 0, 2.5, 10, 25 mg/kg bw/day Route: oral gavage Volume/Vehicle: 5 mL/kg in polyethylene glycol 400 Exposure: 91 days Recovery period: 4 weeks GLP: in compliance Date: 13.09.2005 The animals were observed twic","endpoint":"repeated dose toxicity","ingredient":"HC Orange No. 1","loael_value":"","noael_unit":"mg/kg/day","noael_value":"300","page":15,"route":"oral","species":"rat","study_id":"sccp_o_146_noael_002"}
Regulatory source reproductive toxicity 25 mg/kg bw/d guinea pig - developmental reproductive toxicity SOURCE_SUBDIR=sccp_o_146; REPORT_TITLE=OPINION ON HC Orange n° 1 COLIPA n° B47; OPINION_NUMBER=SCCP/1164/08; COMMITTEE=Scientific Committee on Consumer Products (SCCP); REPORT_DATE=30 September 2008; VALUE_TEXT=25; DOSE=General toxicity The no-observable-adverse-effect-level (NOAEL) for HC Orange n° 1 was determined to be 25 mg/kg bw/d in the 90 study.; EFFECT=Physico-chemical properties HC Orange n° 1 is used as an ingredient in non-oxidative hair dye formulations at levels up to 1%. The stability of HC Orange n° 1 in marketed products is not described. Only one batch of HC Orange n° 1 has been analyzed and characterized. Calculated values of Log Pow cannot be accepted as an estimate of the true physical constant without justification. The absolute content of the dye in any of the batches used is not reported. General toxicity The no-observable-adverse-effect-level (NOAEL) for HC Orange n° 1 was determined to be 25 mg/kg bw/d in the 90 study. In the reproductive studies, the NOAEL for maternal toxicity was 75 mg/kg bw/day and 250 mg/kg bw/day for developmental toxicity. Irritation / sensitisation Under the test conditions, HC Orange n° 1 was not a skin irritant. HC Orange n° 1 is considered to have the potential to produce transient mild eye irritation. No evidence of sensitisation was observed in a Guinea Pig Maximisation Test. It did not induce a hypersensitivity response in an; CITATION_NUMBERS=[]; DETAILS_JSON={"cas_number":"54381-08-7","citation":"","dose":"General toxicity The no-observable-adverse-effect-level (NOAEL) for HC Orange n° 1 was determined to be 25 mg/kg bw/d in the 90 study.","duration":"developmental","effect":"Physico-chemical properties HC Orange n° 1 is used as an ingredient in non-oxidative hair dye formulations at levels up to 1%. The stability of HC Orange n° 1 in marketed products is not described. Only one batch of HC Orange n° 1 has been analyzed and characterized. Calculated values of Log Pow cannot be accepted as an estimate of the true physical constant without justification. The absolute content of the dye in any of the batches used is not reported. General toxicity The no-observable-adverse-effect-level (NOAEL) for HC Orange n° 1 was determined to be 25 mg/kg bw/d in the 90 study. In the reproductive studies, the NOAEL for maternal toxicity was 75 mg/kg bw/day and 250 mg/kg bw/day for developmental toxicity. Irritation / sensitisation Under the test conditions, HC Orange n° 1 was not a skin irritant. HC Orange n° 1 is considered to have the potential to produce transient mild eye irritation. No evidence of sensitisation was observed in a Guinea Pig Maximisation Test. It did not induce a hypersensitivity response in an","endpoint":"reproductive toxicity","ingredient":"HC Orange No. 1","loael_value":"","noael_unit":"mg/kg bw/d","noael_value":"25","page":28,"route":"","species":"guinea pig","study_id":"sccp_o_146_noael_010"}
Regulatory source reproductive toxicity 75 mg/kg bw/day guinea pig - developmental reproductive toxicity SOURCE_SUBDIR=sccp_o_146; REPORT_TITLE=OPINION ON HC Orange n° 1 COLIPA n° B47; OPINION_NUMBER=SCCP/1164/08; COMMITTEE=Scientific Committee on Consumer Products (SCCP); REPORT_DATE=30 September 2008; VALUE_TEXT=75; DOSE=General toxicity The no-observable-adverse-effect-level (NOAEL) for HC Orange n° 1 was determined to be 25 mg/kg bw/d in the 90 study.; EFFECT=levels up to 1%. The stability of HC Orange n° 1 in marketed products is not described. Only one batch of HC Orange n° 1 has been analyzed and characterized. Calculated values of Log Pow cannot be accepted as an estimate of the true physical constant without justification. The absolute content of the dye in any of the batches used is not reported. General toxicity The no-observable-adverse-effect-level (NOAEL) for HC Orange n° 1 was determined to be 25 mg/kg bw/d in the 90 study. In the reproductive studies, the NOAEL for maternal toxicity was 75 mg/kg bw/day and 250 mg/kg bw/day for developmental toxicity. Irritation / sensitisation Under the test conditions, HC Orange n° 1 was not a skin irritant. HC Orange n° 1 is considered to have the potential to produce transient mild eye irritation. No evidence of sensitisation was observed in a Guinea Pig Maximisation Test. It did not induce a hypersensitivity response in an LLNA. However, as the tested concentrations were too low, a skin sensitising potential cannot be excluded. D; CITATION_NUMBERS=[]; DETAILS_JSON={"cas_number":"54381-08-7","citation":"","dose":"General toxicity The no-observable-adverse-effect-level (NOAEL) for HC Orange n° 1 was determined to be 25 mg/kg bw/d in the 90 study.","duration":"developmental","effect":"levels up to 1%. The stability of HC Orange n° 1 in marketed products is not described. Only one batch of HC Orange n° 1 has been analyzed and characterized. Calculated values of Log Pow cannot be accepted as an estimate of the true physical constant without justification. The absolute content of the dye in any of the batches used is not reported. General toxicity The no-observable-adverse-effect-level (NOAEL) for HC Orange n° 1 was determined to be 25 mg/kg bw/d in the 90 study. In the reproductive studies, the NOAEL for maternal toxicity was 75 mg/kg bw/day and 250 mg/kg bw/day for developmental toxicity. Irritation / sensitisation Under the test conditions, HC Orange n° 1 was not a skin irritant. HC Orange n° 1 is considered to have the potential to produce transient mild eye irritation. No evidence of sensitisation was observed in a Guinea Pig Maximisation Test. It did not induce a hypersensitivity response in an LLNA. However, as the tested concentrations were too low, a skin sensitising potential cannot be excluded. D","endpoint":"reproductive toxicity","ingredient":"HC Orange No. 1","loael_value":"","noael_unit":"mg/kg bw/day","noael_value":"75","page":28,"route":"","species":"guinea pig","study_id":"sccp_o_146_noael_011"}
openFDA substances 4 endpoints
Source Endpoint Type Value Unit Species Route Duration Study Type Reference
openFDA substances FDA UNII substance identifier Z92U49184U UNII - - - chemical {"approval_status":null,"molecular_formula":"C12H10N2O3","source_table":"substance_identifiers_fda","substance_class":"chemical","unii_code":"Z92U49184U"}
openFDA substances FDA UNII substance identifier Z92U49184U UNII - - - chemical {"approval_status":null,"molecular_formula":"C12H10N2O3","source_table":"substance_identifiers_fda","substance_class":"chemical","unii_code":"Z92U49184U"}
openFDA substances FDA UNII substance identifier Z92U49184U UNII - - - chemical {"approval_status":null,"molecular_formula":"C12H10N2O3","source_table":"substance_identifiers_fda","substance_class":"chemical","unii_code":"Z92U49184U"}
openFDA substances FDA UNII substance identifier Z92U49184U UNII - - - chemical {"approval_status":null,"molecular_formula":"C12H10N2O3","source_table":"substance_identifiers_fda","substance_class":"chemical","unii_code":"Z92U49184U"}