NOAEL Studies Cosmetic Ingredient

HC Red No. 18 NOAEL Studies

INCI: HC RED NO. 18

CAS: 1444596-49-9

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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SCCS Opinion 36 endpoints
Source Endpoint Type Value Unit Species Route Duration Study Type Reference
SCCS Opinion NOAEL =100 mg/kg bw/day rat oral Sub-chronic repeated dose toxicity {"dose":"A statistically significant increase in relative liver weights was noted in males at 300(200) mg/kg bw/day and in females from 100 mg/kg bw/day.","effect":"n was decreased in the same animals. Several changes related to the test substance or severely affected health conditions were noted in clinical chemistry. A statistically significant increase in relative liver weights was noted in males at 300(200) mg/kg bw/day and in females from 100 mg/kg bw/day. A statistically significant increase in relative thyroids weights was observed in females at 300(200) mg/kg bw/day. At necropsy, a small spleen was noted in one surviving male at 300(200) mg/kg bw/day). Conclusion The NOAEL was 100 mg/kg bw/day in males and 30 mg/kg bw/day in females under the conditions of this study. Ref. 14 3.3.5.2 Sub-chronic (90 days) toxicity (oral) Guideline: OECD TG 408 (1997) Species/strain: Rats/ Crl:CD(SD) Group size: 15/sex/group (control and high-dose groups), 10/sex/group (other groups) Test substance: FPK-254 Batch: WK120919 Purity: 99.85% Vehicle: 0.5% Methylcellulose solution Dose levels: 0, 3, 30, and 150(75/50) mg/kg bw/day Dose volume: 10 ml/kg bw/day","page":19,"pdf":"sccs_o_193.pdf","row_type":"noael_study","study_id":"sccs_o_193_noael_001"}
SCCS Opinion NOAEL =3 mg/kg bw/day rat oral 91 days genotoxicity {"dose":"Other observed histopathological changes were considered by the study report authors to be secondary changes related to poor health conditions or death, or to be common spontaneous changes found in normal rats, or the lack of dose- relation.","effect":"tion of muscle fibre were not observed in any animals. In the females that died or were sacrificed in moribundity, atrophy, degeneration and/or regeneration of muscle fibre were observed as in the scheduled sacrifice animals. Their grades were minimal to mild. Other observed histopathological changes were considered by the study report authors to be secondary changes related to poor health conditions or death, or to be common spontaneous changes found in normal rats, or the lack of dose- relation. Conclusion The NOAEL of FPK-245 was shown to be 3 mg/kg bw/day in male and female rats after continuous oral administration for 91 days. Ref. 15 SCCS comment The SCCS agrees with the NOAEL of 3 mg/kg bw/day; this NOAEL is used for the MOS calculation. 3.3.5.3 Chronic (> 12 months) toxicity No data 3.3.6 Mutagenicity / Genotoxicity 3.3.6.1 Mutagenicity / Genotoxicity in vitro Bacterial Reverse Mutation Test Guideline: OECD 471, Commission Regulation (EC) 440/2008, B.13/14, Japanese Guidelines Species/strain: Salmonella typhi","page":22,"pdf":"sccs_o_193.pdf","row_type":"noael_study","study_id":"sccs_o_193_noael_002"}
SCCS Opinion NOAEL =50 mg/kg bw/day rat - prenatal developmental toxicity {"dose":"At 50 mg/kg bw/day, relevant reproduction parameter (pre- and post-implantation loss and number of foetuses per dam) were not affected by treatment with the test substance.","effect":"could not be evaluated due to premature termination. At 50 mg/kg bw/day, relevant reproduction parameter (pre- and post-implantation loss and number of foetuses per dam) were not affected by treatment with the test substance. Due to premature termination of the dams at 100 and 200 mg/kg bw/day, no foetus was available for examination. At 50 mg/kg bw/day, no treatment-related effects were observed for the foetal body weight and sex ratio of the foetuses, or external abnormalities and variations. Conclusions: The NOAEL for under the conditions of this prenatal developmental toxicity range-finding study was 50 mg/kg bw/day. Ref. 9 SCCS comment The study report (Harlan study no D59271) demonstrating the stability of the test substance has not been submitted. Prenatal developmental toxicity study in rats Guideline: OECD TG 414 (2001) Species/strain: Rat, RccHanTM: WIST(SPF) Group size: 22 females/group Test substance: FPK-245 Batch: WK120919 Purity: 99.85 % Vehicle: 0.5% carboxymethylcellulose (CMC) aqueous solution Dose levels","page":28,"pdf":"sccs_o_193.pdf","row_type":"noael_study","study_id":"sccs_o_193_noael_005"}
SCCS Opinion NOAEL =77 % rat oral - irritation {"dose":"ely 65 % of the dose from the GI tract.","effect":"ely 65 % of the dose from the GI tract. In bile-duct cannulated rats, approximately 48 %, 29 % and 24 % of the dose was excreted in the bile, urine and faeces, respectively, indicating an oral absorption of up to approximately 77 % of the dose from the GI tract (sum of dose excreted in the bile and the urine). Under the conditions of this toxicokinetic study, an oral absorption of 77% is considered based on the results from the bile-duct cannulated rats. The oral absorption of 77% is used for the correction of the NOAEL for the MoS calculation. 3.3.9.2 Toxicokinetics in humans / 3.3.10 Photo-induced toxicity 3.3.10.1 Phototoxicity / photo-irritation and photosensitisation No data 3.3.10.2 Photomutagenicity / photoclastogenicity No data 3.3.11 Human data No data","page":32,"pdf":"sccs_o_193.pdf","row_type":"noael_study","study_id":"sccs_o_193_noael_007"}
SCCS Opinion NOAEL =3 mg/kg/day rat - 90-day repeated dose toxicity {"dose":"Based on the results from the 90-day repeated dose toxicity study, the NOAEL for FPK-245 is 3 mg/kg/day.” 3.3.13 Safety evaluation (including calculation of the MoS) FPK-245 is only intended as a hair dye ingredient in oxidative hair colouring products at on- head concentrations of up to 1.5%.","effect":"een performed to review the toxicity data related to FPK-245 and to assess the toxicological relevance of treatment-associated changes. The conclusions of the expert in relation to hepatocarcinogenicity are as follows: “The lack of a significant increase in GST-P foci in the livers of the toxicity study rats as well as a negative GST-P medium term carcinogenicity assay provide further support for lack of hepatocarcinogenic potential of FPK-245. Based on the results from the 90-day repeated dose toxicity study, the NOAEL for FPK-245 is 3 mg/kg/day.” 3.3.13 Safety evaluation (including calculation of the MoS) FPK-245 is only intended as a hair dye ingredient in oxidative hair colouring products at on- head concentrations of up to 1.5%. Therefore, the value of 0.973 μg/cm² obtained under oxidative conditions will be used for risk assessment and Margin of Safety (MoS) calculation. CALCULATION OF THE MARGIN OF SAFETY (oxidative conditions) (3 % formulation, on-head concentration 1.5 %) Absorption through the skin A = 1.35 µg/cm","page":35,"pdf":"sccs_o_193.pdf","row_type":"noael_study","study_id":"sccs_o_193_noael_008"}
SCCS Opinion NOAEL =0.013 mg/kg bw rat oral 90-day dermal absorption {"dose":"CALCULATION OF THE MARGIN OF SAFETY (oxidative conditions) (3 % formulation, on-head concentration 1.5 %) Absorption through the skin A = 1.35 µg/cm² Skin Area surface SAS = 580 cm2 Dermal absorption per treatment SAS x A x 0.001 = 0.783 mg Typical body weight of human = 60 kg Systemic exposure dose (SED) SAS x A x 0.001/60 = 0.013 mg/kg bw No o...","effect":"entrations of up to 1.5%. Therefore, the value of 0.973 μg/cm² obtained under oxidative conditions will be used for risk assessment and Margin of Safety (MoS) calculation. CALCULATION OF THE MARGIN OF SAFETY (oxidative conditions) (3 % formulation, on-head concentration 1.5 %) Absorption through the skin A = 1.35 µg/cm² Skin Area surface SAS = 580 cm2 Dermal absorption per treatment SAS x A x 0.001 = 0.783 mg Typical body weight of human = 60 kg Systemic exposure dose (SED) SAS x A x 0.001/60 = 0.013 mg/kg bw No observed adverse effect level NOAEL = 3 mg/kg bw/d (90-day, oral, rat) Bioavailability 77 %* = 2.31 mg/kg bw/d Margin of Safety adjusted NOAEL/SED = 180 * based on toxicokinetic study ref 12. 3.3.14 Discussion Physicochemical properties HC Red 18 is intended to be used as a hair dye ingredient in oxidative hair colouring products at on-head concentrations of up to 1.5%. The reported purity and impurity data on HC Red 18 cannot be accepted in the absence of the study report describing analytical methodology, validation of the method, ref","page":35,"pdf":"sccs_o_193.pdf","row_type":"noael_study","study_id":"sccs_o_193_noael_009"}
SCCS Opinion NOAEL =3 mg/kg bw/d rat oral 90-day dermal absorption {"dose":"CALCULATION OF THE MARGIN OF SAFETY (oxidative conditions) (3 % formulation, on-head concentration 1.5 %) Absorption through the skin A = 1.35 µg/cm² Skin Area surface SAS = 580 cm2 Dermal absorption per treatment SAS x A x 0.001 = 0.783 mg Typical body weight of human = 60 kg Systemic exposure dose (SED) SAS x A x 0.001/60 = 0.013 mg/kg bw No o...","effect":"re, the value of 0.973 μg/cm² obtained under oxidative conditions will be used for risk assessment and Margin of Safety (MoS) calculation. CALCULATION OF THE MARGIN OF SAFETY (oxidative conditions) (3 % formulation, on-head concentration 1.5 %) Absorption through the skin A = 1.35 µg/cm² Skin Area surface SAS = 580 cm2 Dermal absorption per treatment SAS x A x 0.001 = 0.783 mg Typical body weight of human = 60 kg Systemic exposure dose (SED) SAS x A x 0.001/60 = 0.013 mg/kg bw No observed adverse effect level NOAEL = 3 mg/kg bw/d (90-day, oral, rat) Bioavailability 77 %* = 2.31 mg/kg bw/d Margin of Safety adjusted NOAEL/SED = 180 * based on toxicokinetic study ref 12. 3.3.14 Discussion Physicochemical properties HC Red 18 is intended to be used as a hair dye ingredient in oxidative hair colouring products at on-head concentrations of up to 1.5%. The reported purity and impurity data on HC Red 18 cannot be accepted in the absence of the study report describing analytical methodology, validation of the method, reference","page":35,"pdf":"sccs_o_193.pdf","row_type":"noael_study","study_id":"sccs_o_193_noael_010"}
SCCS Opinion NOAEL =2.31 mg/kg bw/d rat oral 90-day dermal absorption {"dose":"CALCULATION OF THE MARGIN OF SAFETY (oxidative conditions) (3 % formulation, on-head concentration 1.5 %) Absorption through the skin A = 1.35 µg/cm² Skin Area surface SAS = 580 cm2 Dermal absorption per treatment SAS x A x 0.001 = 0.783 mg Typical body weight of human = 60 kg Systemic exposure dose (SED) SAS x A x 0.001/60 = 0.013 mg/kg bw No o...","effect":"of Safety (MoS) calculation. CALCULATION OF THE MARGIN OF SAFETY (oxidative conditions) (3 % formulation, on-head concentration 1.5 %) Absorption through the skin A = 1.35 µg/cm² Skin Area surface SAS = 580 cm2 Dermal absorption per treatment SAS x A x 0.001 = 0.783 mg Typical body weight of human = 60 kg Systemic exposure dose (SED) SAS x A x 0.001/60 = 0.013 mg/kg bw No observed adverse effect level NOAEL = 3 mg/kg bw/d (90-day, oral, rat) Bioavailability 77 %* = 2.31 mg/kg bw/d Margin of Safety adjusted NOAEL/SED = 180 * based on toxicokinetic study ref 12. 3.3.14 Discussion Physicochemical properties HC Red 18 is intended to be used as a hair dye ingredient in oxidative hair colouring products at on-head concentrations of up to 1.5%. The reported purity and impurity data on HC Red 18 cannot be accepted in the absence of the study report describing analytical methodology, validation of the method, reference standard used for the determination, etc. In addition, further identification data regarding mass spectromet","page":35,"pdf":"sccs_o_193.pdf","row_type":"noael_study","study_id":"sccs_o_193_noael_011"}
SCCS Opinion NOAEL =0.022 mg/kg bw rat oral 90-day NOAEL study {"citation":"(ref. 12)","dose":"culation of the Margin of Safety MOS calculations under oxidative conditions (3 % formulation, on-head concentration 1.5 %) Systemic exposure dose SED = 0.013 mg/kg bw No observed adverse effect level NOAEL = 3 mg/kg bw/d (90-day, oral, rat) Bioavailability 77%* = 2.31 mg/kg bw/d Margin of Safety adjusted NOAEL/SED = 178 * based on the toxicokin...","effect":"culation of the Margin of Safety MOS calculations under oxidative conditions (3 % formulation, on-head concentration 1.5 %) Systemic exposure dose SED = 0.013 mg/kg bw No observed adverse effect level NOAEL = 3 mg/kg bw/d (90-day, oral, rat) Bioavailability 77%* = 2.31 mg/kg bw/d Margin of Safety adjusted NOAEL/SED = 178 * based on the toxicokinetic study (ref. 12) MOS calculations under non-oxidative conditions (0.5% formulation, on head concentration 0.5%) Systemic exposure dose (SED) SED = 0.022 mg/kg bw No observed adverse effect level NOAEL = 3 mg/kg bw/d (90-day, oral, rat) Bioavailability 77%* = 2.31 mg/kg bw/d Margin of Safety adjusted NOAEL/SED = 105 * based on the toxicokinetic study (ref. 12) 3.3.3 Discussion • Based on the additional physicochemical data provided by the Applicant, the SCCS agrees that the purity of the new commercial batches has been improved and only one impurity is detected at 526 nm (Impurity 1B). • The test substance, HC Red 18, as indicated by the provided HPLC-PDA data, in the presence of alkaline peroxide for","page":35,"pdf":"sccs_o_295.pdf","row_type":"noael_study","study_id":"sccs_o_295_noael_005"}
SCCS Opinion NOAEL =100 mg/kg bw/day rat oral Sub-chronic repeated dose toxicity {"dose":"A statistically significant increase in relative liver weights was noted in males at 300(200) mg/kg bw/day and in females from 100 mg/kg bw/day.","effect":"n was decreased in the same animals. Several changes related to the test substance or severely affected health conditions were noted in clinical chemistry. A statistically significant increase in relative liver weights was noted in males at 300(200) mg/kg bw/day and in females from 100 mg/kg bw/day. A statistically significant increase in relative thyroids weights was observed in females at 300(200) mg/kg bw/day. At necropsy, a small spleen was noted in one surviving male at 300(200) mg/kg bw/day). Conclusion The NOAEL was 100 mg/kg bw/day in males and 30 mg/kg bw/day in females under the conditions of this study. Ref. 14 3.3.5.2 Sub-chronic (90 days) toxicity (oral) Guideline: OECD TG 408 (1997) Species/strain: Rats/ Crl:CD(SD) Group size: 15/sex/group (control and high-dose groups), 10/sex/group (other groups) Test substance: FPK-254 Batch: WK120919 Purity: 99.85% Vehicle: 0.5% Methylcellulose solution Dose levels: 0, 3, 30, and 150(75/50) mg/kg bw/day Dose volume: 10 ml/kg bw/day","page":19,"pdf":"sccs_o_193.pdf","row_type":"noael_study","study_id":"sccs_o_193_noael_001"}
SCCS Opinion NOAEL =3 mg/kg bw/day rat oral 91 days genotoxicity {"dose":"Other observed histopathological changes were considered by the study report authors to be secondary changes related to poor health conditions or death, or to be common spontaneous changes found in normal rats, or the lack of dose- relation.","effect":"tion of muscle fibre were not observed in any animals. In the females that died or were sacrificed in moribundity, atrophy, degeneration and/or regeneration of muscle fibre were observed as in the scheduled sacrifice animals. Their grades were minimal to mild. Other observed histopathological changes were considered by the study report authors to be secondary changes related to poor health conditions or death, or to be common spontaneous changes found in normal rats, or the lack of dose- relation. Conclusion The NOAEL of FPK-245 was shown to be 3 mg/kg bw/day in male and female rats after continuous oral administration for 91 days. Ref. 15 SCCS comment The SCCS agrees with the NOAEL of 3 mg/kg bw/day; this NOAEL is used for the MOS calculation. 3.3.5.3 Chronic (> 12 months) toxicity No data 3.3.6 Mutagenicity / Genotoxicity 3.3.6.1 Mutagenicity / Genotoxicity in vitro Bacterial Reverse Mutation Test Guideline: OECD 471, Commission Regulation (EC) 440/2008, B.13/14, Japanese Guidelines Species/strain: Salmonella typhi","page":22,"pdf":"sccs_o_193.pdf","row_type":"noael_study","study_id":"sccs_o_193_noael_002"}
SCCS Opinion NOAEL =50 mg/kg bw/day rat - prenatal developmental toxicity {"dose":"At 50 mg/kg bw/day, relevant reproduction parameter (pre- and post-implantation loss and number of foetuses per dam) were not affected by treatment with the test substance.","effect":"could not be evaluated due to premature termination. At 50 mg/kg bw/day, relevant reproduction parameter (pre- and post-implantation loss and number of foetuses per dam) were not affected by treatment with the test substance. Due to premature termination of the dams at 100 and 200 mg/kg bw/day, no foetus was available for examination. At 50 mg/kg bw/day, no treatment-related effects were observed for the foetal body weight and sex ratio of the foetuses, or external abnormalities and variations. Conclusions: The NOAEL for under the conditions of this prenatal developmental toxicity range-finding study was 50 mg/kg bw/day. Ref. 9 SCCS comment The study report (Harlan study no D59271) demonstrating the stability of the test substance has not been submitted. Prenatal developmental toxicity study in rats Guideline: OECD TG 414 (2001) Species/strain: Rat, RccHanTM: WIST(SPF) Group size: 22 females/group Test substance: FPK-245 Batch: WK120919 Purity: 99.85 % Vehicle: 0.5% carboxymethylcellulose (CMC) aqueous solution Dose levels","page":28,"pdf":"sccs_o_193.pdf","row_type":"noael_study","study_id":"sccs_o_193_noael_005"}
SCCS Opinion NOAEL =77 % rat oral - irritation {"dose":"ely 65 % of the dose from the GI tract.","effect":"ely 65 % of the dose from the GI tract. In bile-duct cannulated rats, approximately 48 %, 29 % and 24 % of the dose was excreted in the bile, urine and faeces, respectively, indicating an oral absorption of up to approximately 77 % of the dose from the GI tract (sum of dose excreted in the bile and the urine). Under the conditions of this toxicokinetic study, an oral absorption of 77% is considered based on the results from the bile-duct cannulated rats. The oral absorption of 77% is used for the correction of the NOAEL for the MoS calculation. 3.3.9.2 Toxicokinetics in humans / 3.3.10 Photo-induced toxicity 3.3.10.1 Phototoxicity / photo-irritation and photosensitisation No data 3.3.10.2 Photomutagenicity / photoclastogenicity No data 3.3.11 Human data No data","page":32,"pdf":"sccs_o_193.pdf","row_type":"noael_study","study_id":"sccs_o_193_noael_007"}
SCCS Opinion NOAEL =3 mg/kg/day rat - 90-day repeated dose toxicity {"dose":"Based on the results from the 90-day repeated dose toxicity study, the NOAEL for FPK-245 is 3 mg/kg/day.” 3.3.13 Safety evaluation (including calculation of the MoS) FPK-245 is only intended as a hair dye ingredient in oxidative hair colouring products at on- head concentrations of up to 1.5%.","effect":"een performed to review the toxicity data related to FPK-245 and to assess the toxicological relevance of treatment-associated changes. The conclusions of the expert in relation to hepatocarcinogenicity are as follows: “The lack of a significant increase in GST-P foci in the livers of the toxicity study rats as well as a negative GST-P medium term carcinogenicity assay provide further support for lack of hepatocarcinogenic potential of FPK-245. Based on the results from the 90-day repeated dose toxicity study, the NOAEL for FPK-245 is 3 mg/kg/day.” 3.3.13 Safety evaluation (including calculation of the MoS) FPK-245 is only intended as a hair dye ingredient in oxidative hair colouring products at on- head concentrations of up to 1.5%. Therefore, the value of 0.973 μg/cm² obtained under oxidative conditions will be used for risk assessment and Margin of Safety (MoS) calculation. CALCULATION OF THE MARGIN OF SAFETY (oxidative conditions) (3 % formulation, on-head concentration 1.5 %) Absorption through the skin A = 1.35 µg/cm","page":35,"pdf":"sccs_o_193.pdf","row_type":"noael_study","study_id":"sccs_o_193_noael_008"}
SCCS Opinion NOAEL =0.013 mg/kg bw rat oral 90-day dermal absorption {"dose":"CALCULATION OF THE MARGIN OF SAFETY (oxidative conditions) (3 % formulation, on-head concentration 1.5 %) Absorption through the skin A = 1.35 µg/cm² Skin Area surface SAS = 580 cm2 Dermal absorption per treatment SAS x A x 0.001 = 0.783 mg Typical body weight of human = 60 kg Systemic exposure dose (SED) SAS x A x 0.001/60 = 0.013 mg/kg bw No o...","effect":"entrations of up to 1.5%. Therefore, the value of 0.973 μg/cm² obtained under oxidative conditions will be used for risk assessment and Margin of Safety (MoS) calculation. CALCULATION OF THE MARGIN OF SAFETY (oxidative conditions) (3 % formulation, on-head concentration 1.5 %) Absorption through the skin A = 1.35 µg/cm² Skin Area surface SAS = 580 cm2 Dermal absorption per treatment SAS x A x 0.001 = 0.783 mg Typical body weight of human = 60 kg Systemic exposure dose (SED) SAS x A x 0.001/60 = 0.013 mg/kg bw No observed adverse effect level NOAEL = 3 mg/kg bw/d (90-day, oral, rat) Bioavailability 77 %* = 2.31 mg/kg bw/d Margin of Safety adjusted NOAEL/SED = 180 * based on toxicokinetic study ref 12. 3.3.14 Discussion Physicochemical properties HC Red 18 is intended to be used as a hair dye ingredient in oxidative hair colouring products at on-head concentrations of up to 1.5%. The reported purity and impurity data on HC Red 18 cannot be accepted in the absence of the study report describing analytical methodology, validation of the method, ref","page":35,"pdf":"sccs_o_193.pdf","row_type":"noael_study","study_id":"sccs_o_193_noael_009"}
SCCS Opinion NOAEL =3 mg/kg bw/d rat oral 90-day dermal absorption {"dose":"CALCULATION OF THE MARGIN OF SAFETY (oxidative conditions) (3 % formulation, on-head concentration 1.5 %) Absorption through the skin A = 1.35 µg/cm² Skin Area surface SAS = 580 cm2 Dermal absorption per treatment SAS x A x 0.001 = 0.783 mg Typical body weight of human = 60 kg Systemic exposure dose (SED) SAS x A x 0.001/60 = 0.013 mg/kg bw No o...","effect":"re, the value of 0.973 μg/cm² obtained under oxidative conditions will be used for risk assessment and Margin of Safety (MoS) calculation. CALCULATION OF THE MARGIN OF SAFETY (oxidative conditions) (3 % formulation, on-head concentration 1.5 %) Absorption through the skin A = 1.35 µg/cm² Skin Area surface SAS = 580 cm2 Dermal absorption per treatment SAS x A x 0.001 = 0.783 mg Typical body weight of human = 60 kg Systemic exposure dose (SED) SAS x A x 0.001/60 = 0.013 mg/kg bw No observed adverse effect level NOAEL = 3 mg/kg bw/d (90-day, oral, rat) Bioavailability 77 %* = 2.31 mg/kg bw/d Margin of Safety adjusted NOAEL/SED = 180 * based on toxicokinetic study ref 12. 3.3.14 Discussion Physicochemical properties HC Red 18 is intended to be used as a hair dye ingredient in oxidative hair colouring products at on-head concentrations of up to 1.5%. The reported purity and impurity data on HC Red 18 cannot be accepted in the absence of the study report describing analytical methodology, validation of the method, reference","page":35,"pdf":"sccs_o_193.pdf","row_type":"noael_study","study_id":"sccs_o_193_noael_010"}
SCCS Opinion NOAEL =2.31 mg/kg bw/d rat oral 90-day dermal absorption {"dose":"CALCULATION OF THE MARGIN OF SAFETY (oxidative conditions) (3 % formulation, on-head concentration 1.5 %) Absorption through the skin A = 1.35 µg/cm² Skin Area surface SAS = 580 cm2 Dermal absorption per treatment SAS x A x 0.001 = 0.783 mg Typical body weight of human = 60 kg Systemic exposure dose (SED) SAS x A x 0.001/60 = 0.013 mg/kg bw No o...","effect":"of Safety (MoS) calculation. CALCULATION OF THE MARGIN OF SAFETY (oxidative conditions) (3 % formulation, on-head concentration 1.5 %) Absorption through the skin A = 1.35 µg/cm² Skin Area surface SAS = 580 cm2 Dermal absorption per treatment SAS x A x 0.001 = 0.783 mg Typical body weight of human = 60 kg Systemic exposure dose (SED) SAS x A x 0.001/60 = 0.013 mg/kg bw No observed adverse effect level NOAEL = 3 mg/kg bw/d (90-day, oral, rat) Bioavailability 77 %* = 2.31 mg/kg bw/d Margin of Safety adjusted NOAEL/SED = 180 * based on toxicokinetic study ref 12. 3.3.14 Discussion Physicochemical properties HC Red 18 is intended to be used as a hair dye ingredient in oxidative hair colouring products at on-head concentrations of up to 1.5%. The reported purity and impurity data on HC Red 18 cannot be accepted in the absence of the study report describing analytical methodology, validation of the method, reference standard used for the determination, etc. In addition, further identification data regarding mass spectromet","page":35,"pdf":"sccs_o_193.pdf","row_type":"noael_study","study_id":"sccs_o_193_noael_011"}
SCCS Opinion NOAEL =100 mg/kg bw/day rat oral Sub-chronic repeated dose toxicity {"dose":"A statistically significant increase in relative liver weights was noted in males at 300(200) mg/kg bw/day and in females from 100 mg/kg bw/day.","effect":"n was decreased in the same animals. Several changes related to the test substance or severely affected health conditions were noted in clinical chemistry. A statistically significant increase in relative liver weights was noted in males at 300(200) mg/kg bw/day and in females from 100 mg/kg bw/day. A statistically significant increase in relative thyroids weights was observed in females at 300(200) mg/kg bw/day. At necropsy, a small spleen was noted in one surviving male at 300(200) mg/kg bw/day). Conclusion The NOAEL was 100 mg/kg bw/day in males and 30 mg/kg bw/day in females under the conditions of this study. Ref. 14 3.3.5.2 Sub-chronic (90 days) toxicity (oral) Guideline: OECD TG 408 (1997) Species/strain: Rats/ Crl:CD(SD) Group size: 15/sex/group (control and high-dose groups), 10/sex/group (other groups) Test substance: FPK-254 Batch: WK120919 Purity: 99.85% Vehicle: 0.5% Methylcellulose solution Dose levels: 0, 3, 30, and 150(75/50) mg/kg bw/day Dose volume: 10 ml/kg bw/day","page":19,"pdf":"sccs_o_193.pdf","row_type":"noael_study","study_id":"sccs_o_193_noael_001"}
SCCS Opinion NOAEL =3 mg/kg bw/day rat oral 91 days genotoxicity {"dose":"Other observed histopathological changes were considered by the study report authors to be secondary changes related to poor health conditions or death, or to be common spontaneous changes found in normal rats, or the lack of dose- relation.","effect":"tion of muscle fibre were not observed in any animals. In the females that died or were sacrificed in moribundity, atrophy, degeneration and/or regeneration of muscle fibre were observed as in the scheduled sacrifice animals. Their grades were minimal to mild. Other observed histopathological changes were considered by the study report authors to be secondary changes related to poor health conditions or death, or to be common spontaneous changes found in normal rats, or the lack of dose- relation. Conclusion The NOAEL of FPK-245 was shown to be 3 mg/kg bw/day in male and female rats after continuous oral administration for 91 days. Ref. 15 SCCS comment The SCCS agrees with the NOAEL of 3 mg/kg bw/day; this NOAEL is used for the MOS calculation. 3.3.5.3 Chronic (> 12 months) toxicity No data 3.3.6 Mutagenicity / Genotoxicity 3.3.6.1 Mutagenicity / Genotoxicity in vitro Bacterial Reverse Mutation Test Guideline: OECD 471, Commission Regulation (EC) 440/2008, B.13/14, Japanese Guidelines Species/strain: Salmonella typhi","page":22,"pdf":"sccs_o_193.pdf","row_type":"noael_study","study_id":"sccs_o_193_noael_002"}
SCCS Opinion NOAEL =50 mg/kg bw/day rat - prenatal developmental toxicity {"dose":"At 50 mg/kg bw/day, relevant reproduction parameter (pre- and post-implantation loss and number of foetuses per dam) were not affected by treatment with the test substance.","effect":"could not be evaluated due to premature termination. At 50 mg/kg bw/day, relevant reproduction parameter (pre- and post-implantation loss and number of foetuses per dam) were not affected by treatment with the test substance. Due to premature termination of the dams at 100 and 200 mg/kg bw/day, no foetus was available for examination. At 50 mg/kg bw/day, no treatment-related effects were observed for the foetal body weight and sex ratio of the foetuses, or external abnormalities and variations. Conclusions: The NOAEL for under the conditions of this prenatal developmental toxicity range-finding study was 50 mg/kg bw/day. Ref. 9 SCCS comment The study report (Harlan study no D59271) demonstrating the stability of the test substance has not been submitted. Prenatal developmental toxicity study in rats Guideline: OECD TG 414 (2001) Species/strain: Rat, RccHanTM: WIST(SPF) Group size: 22 females/group Test substance: FPK-245 Batch: WK120919 Purity: 99.85 % Vehicle: 0.5% carboxymethylcellulose (CMC) aqueous solution Dose levels","page":28,"pdf":"sccs_o_193.pdf","row_type":"noael_study","study_id":"sccs_o_193_noael_005"}
SCCS Opinion NOAEL =77 % rat oral - irritation {"dose":"ely 65 % of the dose from the GI tract.","effect":"ely 65 % of the dose from the GI tract. In bile-duct cannulated rats, approximately 48 %, 29 % and 24 % of the dose was excreted in the bile, urine and faeces, respectively, indicating an oral absorption of up to approximately 77 % of the dose from the GI tract (sum of dose excreted in the bile and the urine). Under the conditions of this toxicokinetic study, an oral absorption of 77% is considered based on the results from the bile-duct cannulated rats. The oral absorption of 77% is used for the correction of the NOAEL for the MoS calculation. 3.3.9.2 Toxicokinetics in humans / 3.3.10 Photo-induced toxicity 3.3.10.1 Phototoxicity / photo-irritation and photosensitisation No data 3.3.10.2 Photomutagenicity / photoclastogenicity No data 3.3.11 Human data No data","page":32,"pdf":"sccs_o_193.pdf","row_type":"noael_study","study_id":"sccs_o_193_noael_007"}
SCCS Opinion NOAEL =3 mg/kg/day rat - 90-day repeated dose toxicity {"dose":"Based on the results from the 90-day repeated dose toxicity study, the NOAEL for FPK-245 is 3 mg/kg/day.” 3.3.13 Safety evaluation (including calculation of the MoS) FPK-245 is only intended as a hair dye ingredient in oxidative hair colouring products at on- head concentrations of up to 1.5%.","effect":"een performed to review the toxicity data related to FPK-245 and to assess the toxicological relevance of treatment-associated changes. The conclusions of the expert in relation to hepatocarcinogenicity are as follows: “The lack of a significant increase in GST-P foci in the livers of the toxicity study rats as well as a negative GST-P medium term carcinogenicity assay provide further support for lack of hepatocarcinogenic potential of FPK-245. Based on the results from the 90-day repeated dose toxicity study, the NOAEL for FPK-245 is 3 mg/kg/day.” 3.3.13 Safety evaluation (including calculation of the MoS) FPK-245 is only intended as a hair dye ingredient in oxidative hair colouring products at on- head concentrations of up to 1.5%. Therefore, the value of 0.973 μg/cm² obtained under oxidative conditions will be used for risk assessment and Margin of Safety (MoS) calculation. CALCULATION OF THE MARGIN OF SAFETY (oxidative conditions) (3 % formulation, on-head concentration 1.5 %) Absorption through the skin A = 1.35 µg/cm","page":35,"pdf":"sccs_o_193.pdf","row_type":"noael_study","study_id":"sccs_o_193_noael_008"}
SCCS Opinion NOAEL =0.013 mg/kg bw rat oral 90-day dermal absorption {"dose":"CALCULATION OF THE MARGIN OF SAFETY (oxidative conditions) (3 % formulation, on-head concentration 1.5 %) Absorption through the skin A = 1.35 µg/cm² Skin Area surface SAS = 580 cm2 Dermal absorption per treatment SAS x A x 0.001 = 0.783 mg Typical body weight of human = 60 kg Systemic exposure dose (SED) SAS x A x 0.001/60 = 0.013 mg/kg bw No o...","effect":"entrations of up to 1.5%. Therefore, the value of 0.973 μg/cm² obtained under oxidative conditions will be used for risk assessment and Margin of Safety (MoS) calculation. CALCULATION OF THE MARGIN OF SAFETY (oxidative conditions) (3 % formulation, on-head concentration 1.5 %) Absorption through the skin A = 1.35 µg/cm² Skin Area surface SAS = 580 cm2 Dermal absorption per treatment SAS x A x 0.001 = 0.783 mg Typical body weight of human = 60 kg Systemic exposure dose (SED) SAS x A x 0.001/60 = 0.013 mg/kg bw No observed adverse effect level NOAEL = 3 mg/kg bw/d (90-day, oral, rat) Bioavailability 77 %* = 2.31 mg/kg bw/d Margin of Safety adjusted NOAEL/SED = 180 * based on toxicokinetic study ref 12. 3.3.14 Discussion Physicochemical properties HC Red 18 is intended to be used as a hair dye ingredient in oxidative hair colouring products at on-head concentrations of up to 1.5%. The reported purity and impurity data on HC Red 18 cannot be accepted in the absence of the study report describing analytical methodology, validation of the method, ref","page":35,"pdf":"sccs_o_193.pdf","row_type":"noael_study","study_id":"sccs_o_193_noael_009"}
SCCS Opinion NOAEL =3 mg/kg bw/d rat oral 90-day dermal absorption {"dose":"CALCULATION OF THE MARGIN OF SAFETY (oxidative conditions) (3 % formulation, on-head concentration 1.5 %) Absorption through the skin A = 1.35 µg/cm² Skin Area surface SAS = 580 cm2 Dermal absorption per treatment SAS x A x 0.001 = 0.783 mg Typical body weight of human = 60 kg Systemic exposure dose (SED) SAS x A x 0.001/60 = 0.013 mg/kg bw No o...","effect":"re, the value of 0.973 μg/cm² obtained under oxidative conditions will be used for risk assessment and Margin of Safety (MoS) calculation. CALCULATION OF THE MARGIN OF SAFETY (oxidative conditions) (3 % formulation, on-head concentration 1.5 %) Absorption through the skin A = 1.35 µg/cm² Skin Area surface SAS = 580 cm2 Dermal absorption per treatment SAS x A x 0.001 = 0.783 mg Typical body weight of human = 60 kg Systemic exposure dose (SED) SAS x A x 0.001/60 = 0.013 mg/kg bw No observed adverse effect level NOAEL = 3 mg/kg bw/d (90-day, oral, rat) Bioavailability 77 %* = 2.31 mg/kg bw/d Margin of Safety adjusted NOAEL/SED = 180 * based on toxicokinetic study ref 12. 3.3.14 Discussion Physicochemical properties HC Red 18 is intended to be used as a hair dye ingredient in oxidative hair colouring products at on-head concentrations of up to 1.5%. The reported purity and impurity data on HC Red 18 cannot be accepted in the absence of the study report describing analytical methodology, validation of the method, reference","page":35,"pdf":"sccs_o_193.pdf","row_type":"noael_study","study_id":"sccs_o_193_noael_010"}
SCCS Opinion NOAEL =2.31 mg/kg bw/d rat oral 90-day dermal absorption {"dose":"CALCULATION OF THE MARGIN OF SAFETY (oxidative conditions) (3 % formulation, on-head concentration 1.5 %) Absorption through the skin A = 1.35 µg/cm² Skin Area surface SAS = 580 cm2 Dermal absorption per treatment SAS x A x 0.001 = 0.783 mg Typical body weight of human = 60 kg Systemic exposure dose (SED) SAS x A x 0.001/60 = 0.013 mg/kg bw No o...","effect":"of Safety (MoS) calculation. CALCULATION OF THE MARGIN OF SAFETY (oxidative conditions) (3 % formulation, on-head concentration 1.5 %) Absorption through the skin A = 1.35 µg/cm² Skin Area surface SAS = 580 cm2 Dermal absorption per treatment SAS x A x 0.001 = 0.783 mg Typical body weight of human = 60 kg Systemic exposure dose (SED) SAS x A x 0.001/60 = 0.013 mg/kg bw No observed adverse effect level NOAEL = 3 mg/kg bw/d (90-day, oral, rat) Bioavailability 77 %* = 2.31 mg/kg bw/d Margin of Safety adjusted NOAEL/SED = 180 * based on toxicokinetic study ref 12. 3.3.14 Discussion Physicochemical properties HC Red 18 is intended to be used as a hair dye ingredient in oxidative hair colouring products at on-head concentrations of up to 1.5%. The reported purity and impurity data on HC Red 18 cannot be accepted in the absence of the study report describing analytical methodology, validation of the method, reference standard used for the determination, etc. In addition, further identification data regarding mass spectromet","page":35,"pdf":"sccs_o_193.pdf","row_type":"noael_study","study_id":"sccs_o_193_noael_011"}
SCCS Opinion NOAEL =0.022 mg/kg bw rat oral 90-day NOAEL study {"citation":"(ref. 12)","dose":"culation of the Margin of Safety MOS calculations under oxidative conditions (3 % formulation, on-head concentration 1.5 %) Systemic exposure dose SED = 0.013 mg/kg bw No observed adverse effect level NOAEL = 3 mg/kg bw/d (90-day, oral, rat) Bioavailability 77%* = 2.31 mg/kg bw/d Margin of Safety adjusted NOAEL/SED = 178 * based on the toxicokin...","effect":"culation of the Margin of Safety MOS calculations under oxidative conditions (3 % formulation, on-head concentration 1.5 %) Systemic exposure dose SED = 0.013 mg/kg bw No observed adverse effect level NOAEL = 3 mg/kg bw/d (90-day, oral, rat) Bioavailability 77%* = 2.31 mg/kg bw/d Margin of Safety adjusted NOAEL/SED = 178 * based on the toxicokinetic study (ref. 12) MOS calculations under non-oxidative conditions (0.5% formulation, on head concentration 0.5%) Systemic exposure dose (SED) SED = 0.022 mg/kg bw No observed adverse effect level NOAEL = 3 mg/kg bw/d (90-day, oral, rat) Bioavailability 77%* = 2.31 mg/kg bw/d Margin of Safety adjusted NOAEL/SED = 105 * based on the toxicokinetic study (ref. 12) 3.3.3 Discussion • Based on the additional physicochemical data provided by the Applicant, the SCCS agrees that the purity of the new commercial batches has been improved and only one impurity is detected at 526 nm (Impurity 1B). • The test substance, HC Red 18, as indicated by the provided HPLC-PDA data, in the presence of alkaline peroxide for","page":35,"pdf":"sccs_o_295.pdf","row_type":"noael_study","study_id":"sccs_o_295_noael_005"}
SCCS Opinion NOAEL =0.022 mg/kg bw rat oral 90-day NOAEL study {"citation":"(ref. 12)","dose":"culation of the Margin of Safety MOS calculations under oxidative conditions (3 % formulation, on-head concentration 1.5 %) Systemic exposure dose SED = 0.013 mg/kg bw No observed adverse effect level NOAEL = 3 mg/kg bw/d (90-day, oral, rat) Bioavailability 77%* = 2.31 mg/kg bw/d Margin of Safety adjusted NOAEL/SED = 178 * based on the toxicokin...","effect":"culation of the Margin of Safety MOS calculations under oxidative conditions (3 % formulation, on-head concentration 1.5 %) Systemic exposure dose SED = 0.013 mg/kg bw No observed adverse effect level NOAEL = 3 mg/kg bw/d (90-day, oral, rat) Bioavailability 77%* = 2.31 mg/kg bw/d Margin of Safety adjusted NOAEL/SED = 178 * based on the toxicokinetic study (ref. 12) MOS calculations under non-oxidative conditions (0.5% formulation, on head concentration 0.5%) Systemic exposure dose (SED) SED = 0.022 mg/kg bw No observed adverse effect level NOAEL = 3 mg/kg bw/d (90-day, oral, rat) Bioavailability 77%* = 2.31 mg/kg bw/d Margin of Safety adjusted NOAEL/SED = 105 * based on the toxicokinetic study (ref. 12) 3.3.3 Discussion • Based on the additional physicochemical data provided by the Applicant, the SCCS agrees that the purity of the new commercial batches has been improved and only one impurity is detected at 526 nm (Impurity 1B). • The test substance, HC Red 18, as indicated by the provided HPLC-PDA data, in the presence of alkaline peroxide for","page":35,"pdf":"sccs_o_295.pdf","row_type":"noael_study","study_id":"sccs_o_295_noael_005"}
SCCS Opinion NOAEL =100 mg/kg bw/day rat oral Sub-chronic repeated dose toxicity {"dose":"A statistically significant increase in relative liver weights was noted in males at 300(200) mg/kg bw/day and in females from 100 mg/kg bw/day.","effect":"n was decreased in the same animals. Several changes related to the test substance or severely affected health conditions were noted in clinical chemistry. A statistically significant increase in relative liver weights was noted in males at 300(200) mg/kg bw/day and in females from 100 mg/kg bw/day. A statistically significant increase in relative thyroids weights was observed in females at 300(200) mg/kg bw/day. At necropsy, a small spleen was noted in one surviving male at 300(200) mg/kg bw/day). Conclusion The NOAEL was 100 mg/kg bw/day in males and 30 mg/kg bw/day in females under the conditions of this study. Ref. 14 3.3.5.2 Sub-chronic (90 days) toxicity (oral) Guideline: OECD TG 408 (1997) Species/strain: Rats/ Crl:CD(SD) Group size: 15/sex/group (control and high-dose groups), 10/sex/group (other groups) Test substance: FPK-254 Batch: WK120919 Purity: 99.85% Vehicle: 0.5% Methylcellulose solution Dose levels: 0, 3, 30, and 150(75/50) mg/kg bw/day Dose volume: 10 ml/kg bw/day","page":19,"pdf":"sccs_o_193.pdf","row_type":"noael_study","study_id":"sccs_o_193_noael_001"}
SCCS Opinion NOAEL =3 mg/kg bw/day rat oral 91 days genotoxicity {"dose":"Other observed histopathological changes were considered by the study report authors to be secondary changes related to poor health conditions or death, or to be common spontaneous changes found in normal rats, or the lack of dose- relation.","effect":"tion of muscle fibre were not observed in any animals. In the females that died or were sacrificed in moribundity, atrophy, degeneration and/or regeneration of muscle fibre were observed as in the scheduled sacrifice animals. Their grades were minimal to mild. Other observed histopathological changes were considered by the study report authors to be secondary changes related to poor health conditions or death, or to be common spontaneous changes found in normal rats, or the lack of dose- relation. Conclusion The NOAEL of FPK-245 was shown to be 3 mg/kg bw/day in male and female rats after continuous oral administration for 91 days. Ref. 15 SCCS comment The SCCS agrees with the NOAEL of 3 mg/kg bw/day; this NOAEL is used for the MOS calculation. 3.3.5.3 Chronic (> 12 months) toxicity No data 3.3.6 Mutagenicity / Genotoxicity 3.3.6.1 Mutagenicity / Genotoxicity in vitro Bacterial Reverse Mutation Test Guideline: OECD 471, Commission Regulation (EC) 440/2008, B.13/14, Japanese Guidelines Species/strain: Salmonella typhi","page":22,"pdf":"sccs_o_193.pdf","row_type":"noael_study","study_id":"sccs_o_193_noael_002"}
SCCS Opinion NOAEL =50 mg/kg bw/day rat - prenatal developmental toxicity {"dose":"At 50 mg/kg bw/day, relevant reproduction parameter (pre- and post-implantation loss and number of foetuses per dam) were not affected by treatment with the test substance.","effect":"could not be evaluated due to premature termination. At 50 mg/kg bw/day, relevant reproduction parameter (pre- and post-implantation loss and number of foetuses per dam) were not affected by treatment with the test substance. Due to premature termination of the dams at 100 and 200 mg/kg bw/day, no foetus was available for examination. At 50 mg/kg bw/day, no treatment-related effects were observed for the foetal body weight and sex ratio of the foetuses, or external abnormalities and variations. Conclusions: The NOAEL for under the conditions of this prenatal developmental toxicity range-finding study was 50 mg/kg bw/day. Ref. 9 SCCS comment The study report (Harlan study no D59271) demonstrating the stability of the test substance has not been submitted. Prenatal developmental toxicity study in rats Guideline: OECD TG 414 (2001) Species/strain: Rat, RccHanTM: WIST(SPF) Group size: 22 females/group Test substance: FPK-245 Batch: WK120919 Purity: 99.85 % Vehicle: 0.5% carboxymethylcellulose (CMC) aqueous solution Dose levels","page":28,"pdf":"sccs_o_193.pdf","row_type":"noael_study","study_id":"sccs_o_193_noael_005"}
SCCS Opinion NOAEL =77 % rat oral - irritation {"dose":"ely 65 % of the dose from the GI tract.","effect":"ely 65 % of the dose from the GI tract. In bile-duct cannulated rats, approximately 48 %, 29 % and 24 % of the dose was excreted in the bile, urine and faeces, respectively, indicating an oral absorption of up to approximately 77 % of the dose from the GI tract (sum of dose excreted in the bile and the urine). Under the conditions of this toxicokinetic study, an oral absorption of 77% is considered based on the results from the bile-duct cannulated rats. The oral absorption of 77% is used for the correction of the NOAEL for the MoS calculation. 3.3.9.2 Toxicokinetics in humans / 3.3.10 Photo-induced toxicity 3.3.10.1 Phototoxicity / photo-irritation and photosensitisation No data 3.3.10.2 Photomutagenicity / photoclastogenicity No data 3.3.11 Human data No data","page":32,"pdf":"sccs_o_193.pdf","row_type":"noael_study","study_id":"sccs_o_193_noael_007"}
SCCS Opinion NOAEL =3 mg/kg/day rat - 90-day repeated dose toxicity {"dose":"Based on the results from the 90-day repeated dose toxicity study, the NOAEL for FPK-245 is 3 mg/kg/day.” 3.3.13 Safety evaluation (including calculation of the MoS) FPK-245 is only intended as a hair dye ingredient in oxidative hair colouring products at on- head concentrations of up to 1.5%.","effect":"een performed to review the toxicity data related to FPK-245 and to assess the toxicological relevance of treatment-associated changes. The conclusions of the expert in relation to hepatocarcinogenicity are as follows: “The lack of a significant increase in GST-P foci in the livers of the toxicity study rats as well as a negative GST-P medium term carcinogenicity assay provide further support for lack of hepatocarcinogenic potential of FPK-245. Based on the results from the 90-day repeated dose toxicity study, the NOAEL for FPK-245 is 3 mg/kg/day.” 3.3.13 Safety evaluation (including calculation of the MoS) FPK-245 is only intended as a hair dye ingredient in oxidative hair colouring products at on- head concentrations of up to 1.5%. Therefore, the value of 0.973 μg/cm² obtained under oxidative conditions will be used for risk assessment and Margin of Safety (MoS) calculation. CALCULATION OF THE MARGIN OF SAFETY (oxidative conditions) (3 % formulation, on-head concentration 1.5 %) Absorption through the skin A = 1.35 µg/cm","page":35,"pdf":"sccs_o_193.pdf","row_type":"noael_study","study_id":"sccs_o_193_noael_008"}
SCCS Opinion NOAEL =0.013 mg/kg bw rat oral 90-day dermal absorption {"dose":"CALCULATION OF THE MARGIN OF SAFETY (oxidative conditions) (3 % formulation, on-head concentration 1.5 %) Absorption through the skin A = 1.35 µg/cm² Skin Area surface SAS = 580 cm2 Dermal absorption per treatment SAS x A x 0.001 = 0.783 mg Typical body weight of human = 60 kg Systemic exposure dose (SED) SAS x A x 0.001/60 = 0.013 mg/kg bw No o...","effect":"entrations of up to 1.5%. Therefore, the value of 0.973 μg/cm² obtained under oxidative conditions will be used for risk assessment and Margin of Safety (MoS) calculation. CALCULATION OF THE MARGIN OF SAFETY (oxidative conditions) (3 % formulation, on-head concentration 1.5 %) Absorption through the skin A = 1.35 µg/cm² Skin Area surface SAS = 580 cm2 Dermal absorption per treatment SAS x A x 0.001 = 0.783 mg Typical body weight of human = 60 kg Systemic exposure dose (SED) SAS x A x 0.001/60 = 0.013 mg/kg bw No observed adverse effect level NOAEL = 3 mg/kg bw/d (90-day, oral, rat) Bioavailability 77 %* = 2.31 mg/kg bw/d Margin of Safety adjusted NOAEL/SED = 180 * based on toxicokinetic study ref 12. 3.3.14 Discussion Physicochemical properties HC Red 18 is intended to be used as a hair dye ingredient in oxidative hair colouring products at on-head concentrations of up to 1.5%. The reported purity and impurity data on HC Red 18 cannot be accepted in the absence of the study report describing analytical methodology, validation of the method, ref","page":35,"pdf":"sccs_o_193.pdf","row_type":"noael_study","study_id":"sccs_o_193_noael_009"}
SCCS Opinion NOAEL =3 mg/kg bw/d rat oral 90-day dermal absorption {"dose":"CALCULATION OF THE MARGIN OF SAFETY (oxidative conditions) (3 % formulation, on-head concentration 1.5 %) Absorption through the skin A = 1.35 µg/cm² Skin Area surface SAS = 580 cm2 Dermal absorption per treatment SAS x A x 0.001 = 0.783 mg Typical body weight of human = 60 kg Systemic exposure dose (SED) SAS x A x 0.001/60 = 0.013 mg/kg bw No o...","effect":"re, the value of 0.973 μg/cm² obtained under oxidative conditions will be used for risk assessment and Margin of Safety (MoS) calculation. CALCULATION OF THE MARGIN OF SAFETY (oxidative conditions) (3 % formulation, on-head concentration 1.5 %) Absorption through the skin A = 1.35 µg/cm² Skin Area surface SAS = 580 cm2 Dermal absorption per treatment SAS x A x 0.001 = 0.783 mg Typical body weight of human = 60 kg Systemic exposure dose (SED) SAS x A x 0.001/60 = 0.013 mg/kg bw No observed adverse effect level NOAEL = 3 mg/kg bw/d (90-day, oral, rat) Bioavailability 77 %* = 2.31 mg/kg bw/d Margin of Safety adjusted NOAEL/SED = 180 * based on toxicokinetic study ref 12. 3.3.14 Discussion Physicochemical properties HC Red 18 is intended to be used as a hair dye ingredient in oxidative hair colouring products at on-head concentrations of up to 1.5%. The reported purity and impurity data on HC Red 18 cannot be accepted in the absence of the study report describing analytical methodology, validation of the method, reference","page":35,"pdf":"sccs_o_193.pdf","row_type":"noael_study","study_id":"sccs_o_193_noael_010"}
SCCS Opinion NOAEL =2.31 mg/kg bw/d rat oral 90-day dermal absorption {"dose":"CALCULATION OF THE MARGIN OF SAFETY (oxidative conditions) (3 % formulation, on-head concentration 1.5 %) Absorption through the skin A = 1.35 µg/cm² Skin Area surface SAS = 580 cm2 Dermal absorption per treatment SAS x A x 0.001 = 0.783 mg Typical body weight of human = 60 kg Systemic exposure dose (SED) SAS x A x 0.001/60 = 0.013 mg/kg bw No o...","effect":"of Safety (MoS) calculation. CALCULATION OF THE MARGIN OF SAFETY (oxidative conditions) (3 % formulation, on-head concentration 1.5 %) Absorption through the skin A = 1.35 µg/cm² Skin Area surface SAS = 580 cm2 Dermal absorption per treatment SAS x A x 0.001 = 0.783 mg Typical body weight of human = 60 kg Systemic exposure dose (SED) SAS x A x 0.001/60 = 0.013 mg/kg bw No observed adverse effect level NOAEL = 3 mg/kg bw/d (90-day, oral, rat) Bioavailability 77 %* = 2.31 mg/kg bw/d Margin of Safety adjusted NOAEL/SED = 180 * based on toxicokinetic study ref 12. 3.3.14 Discussion Physicochemical properties HC Red 18 is intended to be used as a hair dye ingredient in oxidative hair colouring products at on-head concentrations of up to 1.5%. The reported purity and impurity data on HC Red 18 cannot be accepted in the absence of the study report describing analytical methodology, validation of the method, reference standard used for the determination, etc. In addition, further identification data regarding mass spectromet","page":35,"pdf":"sccs_o_193.pdf","row_type":"noael_study","study_id":"sccs_o_193_noael_011"}
SCCS Opinion NOAEL =0.022 mg/kg bw rat oral 90-day NOAEL study {"citation":"(ref. 12)","dose":"culation of the Margin of Safety MOS calculations under oxidative conditions (3 % formulation, on-head concentration 1.5 %) Systemic exposure dose SED = 0.013 mg/kg bw No observed adverse effect level NOAEL = 3 mg/kg bw/d (90-day, oral, rat) Bioavailability 77%* = 2.31 mg/kg bw/d Margin of Safety adjusted NOAEL/SED = 178 * based on the toxicokin...","effect":"culation of the Margin of Safety MOS calculations under oxidative conditions (3 % formulation, on-head concentration 1.5 %) Systemic exposure dose SED = 0.013 mg/kg bw No observed adverse effect level NOAEL = 3 mg/kg bw/d (90-day, oral, rat) Bioavailability 77%* = 2.31 mg/kg bw/d Margin of Safety adjusted NOAEL/SED = 178 * based on the toxicokinetic study (ref. 12) MOS calculations under non-oxidative conditions (0.5% formulation, on head concentration 0.5%) Systemic exposure dose (SED) SED = 0.022 mg/kg bw No observed adverse effect level NOAEL = 3 mg/kg bw/d (90-day, oral, rat) Bioavailability 77%* = 2.31 mg/kg bw/d Margin of Safety adjusted NOAEL/SED = 105 * based on the toxicokinetic study (ref. 12) 3.3.3 Discussion • Based on the additional physicochemical data provided by the Applicant, the SCCS agrees that the purity of the new commercial batches has been improved and only one impurity is detected at 526 nm (Impurity 1B). • The test substance, HC Red 18, as indicated by the provided HPLC-PDA data, in the presence of alkaline peroxide for","page":35,"pdf":"sccs_o_295.pdf","row_type":"noael_study","study_id":"sccs_o_295_noael_005"}
Regulatory source 15 endpoints
Source Endpoint Type Value Unit Species Route Duration Study Type Reference
Regulatory source dermal absorption =0.013 mg/kg bw rat oral 90-day dermal absorption SOURCE_SUBDIR=sccs_o_193; REPORT_TITLE=OPINION ON HC Red No. 18 (В124); OPINION_NUMBER=SCCS/1569/15; COMMITTEE=Scientific Committee on Consumer Safety (SCCS); REPORT_DATE=16 March 2016; VALUE_TEXT== 0.013; DOSE=CALCULATION OF THE MARGIN OF SAFETY (oxidative conditions) (3 % formulation, on-head concentration 1.5 %) Absorption through the skin A = 1.35 µg/cm² Skin Area surface SAS = 580 cm2 Dermal absorption per treatment SAS x A x 0.001 = 0.783 mg Typical body weight of human = 60 kg Systemic exposure dose (SED) SAS x A x 0.001/60 = 0.013 mg/kg bw No o...; EFFECT=entrations of up to 1.5%. Therefore, the value of 0.973 μg/cm² obtained under oxidative conditions will be used for risk assessment and Margin of Safety (MoS) calculation. CALCULATION OF THE MARGIN OF SAFETY (oxidative conditions) (3 % formulation, on-head concentration 1.5 %) Absorption through the skin A = 1.35 µg/cm² Skin Area surface SAS = 580 cm2 Dermal absorption per treatment SAS x A x 0.001 = 0.783 mg Typical body weight of human = 60 kg Systemic exposure dose (SED) SAS x A x 0.001/60 = 0.013 mg/kg bw No observed adverse effect level NOAEL = 3 mg/kg bw/d (90-day, oral, rat) Bioavailability 77 %* = 2.31 mg/kg bw/d Margin of Safety adjusted NOAEL/SED = 180 * based on toxicokinetic study ref 12. 3.3.14 Discussion Physicochemical properties HC Red 18 is intended to be used as a hair dye ingredient in oxidative hair colouring products at on-head concentrations of up to 1.5%. The reported purity and impurity data on HC Red 18 cannot be accepted in the absence of the study report describing analytical methodology, validation of the method, ref; CITATION_NUMBERS=[]; DETAILS_JSON={"cas_number":"1444596-49-9","citation":"","dose":"CALCULATION OF THE MARGIN OF SAFETY (oxidative conditions) (3 % formulation, on-head concentration 1.5 %) Absorption through the skin A = 1.35 µg/cm² Skin Area surface SAS = 580 cm2 Dermal absorption per treatment SAS x A x 0.001 = 0.783 mg Typical body weight of human = 60 kg Systemic exposure dose (SED) SAS x A x 0.001/60 = 0.013 mg/kg bw No o...","duration":"90-day","effect":"entrations of up to 1.5%. Therefore, the value of 0.973 μg/cm² obtained under oxidative conditions will be used for risk assessment and Margin of Safety (MoS) calculation. CALCULATION OF THE MARGIN OF SAFETY (oxidative conditions) (3 % formulation, on-head concentration 1.5 %) Absorption through the skin A = 1.35 µg/cm² Skin Area surface SAS = 580 cm2 Dermal absorption per treatment SAS x A x 0.001 = 0.783 mg Typical body weight of human = 60 kg Systemic exposure dose (SED) SAS x A x 0.001/60 = 0.013 mg/kg bw No observed adverse effect level NOAEL = 3 mg/kg bw/d (90-day, oral, rat) Bioavailability 77 %* = 2.31 mg/kg bw/d Margin of Safety adjusted NOAEL/SED = 180 * based on toxicokinetic study ref 12. 3.3.14 Discussion Physicochemical properties HC Red 18 is intended to be used as a hair dye ingredient in oxidative hair colouring products at on-head concentrations of up to 1.5%. The reported purity and impurity data on HC Red 18 cannot be accepted in the absence of the study report describing analytical methodology, validation of the method, ref","endpoint":"dermal absorption","ingredient":"HC Red No. 18","loael_value":"","noael_unit":"mg/kg bw","noael_value":"= 0.013","page":35,"route":"oral","species":"rat","study_id":"sccs_o_193_noael_009"}
Regulatory source dermal absorption =3 mg/kg bw/d rat oral 90-day dermal absorption SOURCE_SUBDIR=sccs_o_193; REPORT_TITLE=OPINION ON HC Red No. 18 (В124); OPINION_NUMBER=SCCS/1569/15; COMMITTEE=Scientific Committee on Consumer Safety (SCCS); REPORT_DATE=16 March 2016; VALUE_TEXT== 3; DOSE=CALCULATION OF THE MARGIN OF SAFETY (oxidative conditions) (3 % formulation, on-head concentration 1.5 %) Absorption through the skin A = 1.35 µg/cm² Skin Area surface SAS = 580 cm2 Dermal absorption per treatment SAS x A x 0.001 = 0.783 mg Typical body weight of human = 60 kg Systemic exposure dose (SED) SAS x A x 0.001/60 = 0.013 mg/kg bw No o...; EFFECT=re, the value of 0.973 μg/cm² obtained under oxidative conditions will be used for risk assessment and Margin of Safety (MoS) calculation. CALCULATION OF THE MARGIN OF SAFETY (oxidative conditions) (3 % formulation, on-head concentration 1.5 %) Absorption through the skin A = 1.35 µg/cm² Skin Area surface SAS = 580 cm2 Dermal absorption per treatment SAS x A x 0.001 = 0.783 mg Typical body weight of human = 60 kg Systemic exposure dose (SED) SAS x A x 0.001/60 = 0.013 mg/kg bw No observed adverse effect level NOAEL = 3 mg/kg bw/d (90-day, oral, rat) Bioavailability 77 %* = 2.31 mg/kg bw/d Margin of Safety adjusted NOAEL/SED = 180 * based on toxicokinetic study ref 12. 3.3.14 Discussion Physicochemical properties HC Red 18 is intended to be used as a hair dye ingredient in oxidative hair colouring products at on-head concentrations of up to 1.5%. The reported purity and impurity data on HC Red 18 cannot be accepted in the absence of the study report describing analytical methodology, validation of the method, reference; CITATION_NUMBERS=[]; DETAILS_JSON={"cas_number":"1444596-49-9","citation":"","dose":"CALCULATION OF THE MARGIN OF SAFETY (oxidative conditions) (3 % formulation, on-head concentration 1.5 %) Absorption through the skin A = 1.35 µg/cm² Skin Area surface SAS = 580 cm2 Dermal absorption per treatment SAS x A x 0.001 = 0.783 mg Typical body weight of human = 60 kg Systemic exposure dose (SED) SAS x A x 0.001/60 = 0.013 mg/kg bw No o...","duration":"90-day","effect":"re, the value of 0.973 μg/cm² obtained under oxidative conditions will be used for risk assessment and Margin of Safety (MoS) calculation. CALCULATION OF THE MARGIN OF SAFETY (oxidative conditions) (3 % formulation, on-head concentration 1.5 %) Absorption through the skin A = 1.35 µg/cm² Skin Area surface SAS = 580 cm2 Dermal absorption per treatment SAS x A x 0.001 = 0.783 mg Typical body weight of human = 60 kg Systemic exposure dose (SED) SAS x A x 0.001/60 = 0.013 mg/kg bw No observed adverse effect level NOAEL = 3 mg/kg bw/d (90-day, oral, rat) Bioavailability 77 %* = 2.31 mg/kg bw/d Margin of Safety adjusted NOAEL/SED = 180 * based on toxicokinetic study ref 12. 3.3.14 Discussion Physicochemical properties HC Red 18 is intended to be used as a hair dye ingredient in oxidative hair colouring products at on-head concentrations of up to 1.5%. The reported purity and impurity data on HC Red 18 cannot be accepted in the absence of the study report describing analytical methodology, validation of the method, reference","endpoint":"dermal absorption","ingredient":"HC Red No. 18","loael_value":"","noael_unit":"mg/kg bw/d","noael_value":"= 3","page":35,"route":"oral","species":"rat","study_id":"sccs_o_193_noael_010"}
Regulatory source dermal absorption =2.31 mg/kg bw/d rat oral 90-day dermal absorption SOURCE_SUBDIR=sccs_o_193; REPORT_TITLE=OPINION ON HC Red No. 18 (В124); OPINION_NUMBER=SCCS/1569/15; COMMITTEE=Scientific Committee on Consumer Safety (SCCS); REPORT_DATE=16 March 2016; VALUE_TEXT== 2.31; DOSE=CALCULATION OF THE MARGIN OF SAFETY (oxidative conditions) (3 % formulation, on-head concentration 1.5 %) Absorption through the skin A = 1.35 µg/cm² Skin Area surface SAS = 580 cm2 Dermal absorption per treatment SAS x A x 0.001 = 0.783 mg Typical body weight of human = 60 kg Systemic exposure dose (SED) SAS x A x 0.001/60 = 0.013 mg/kg bw No o...; EFFECT=of Safety (MoS) calculation. CALCULATION OF THE MARGIN OF SAFETY (oxidative conditions) (3 % formulation, on-head concentration 1.5 %) Absorption through the skin A = 1.35 µg/cm² Skin Area surface SAS = 580 cm2 Dermal absorption per treatment SAS x A x 0.001 = 0.783 mg Typical body weight of human = 60 kg Systemic exposure dose (SED) SAS x A x 0.001/60 = 0.013 mg/kg bw No observed adverse effect level NOAEL = 3 mg/kg bw/d (90-day, oral, rat) Bioavailability 77 %* = 2.31 mg/kg bw/d Margin of Safety adjusted NOAEL/SED = 180 * based on toxicokinetic study ref 12. 3.3.14 Discussion Physicochemical properties HC Red 18 is intended to be used as a hair dye ingredient in oxidative hair colouring products at on-head concentrations of up to 1.5%. The reported purity and impurity data on HC Red 18 cannot be accepted in the absence of the study report describing analytical methodology, validation of the method, reference standard used for the determination, etc. In addition, further identification data regarding mass spectromet; CITATION_NUMBERS=[]; DETAILS_JSON={"cas_number":"1444596-49-9","citation":"","dose":"CALCULATION OF THE MARGIN OF SAFETY (oxidative conditions) (3 % formulation, on-head concentration 1.5 %) Absorption through the skin A = 1.35 µg/cm² Skin Area surface SAS = 580 cm2 Dermal absorption per treatment SAS x A x 0.001 = 0.783 mg Typical body weight of human = 60 kg Systemic exposure dose (SED) SAS x A x 0.001/60 = 0.013 mg/kg bw No o...","duration":"90-day","effect":"of Safety (MoS) calculation. CALCULATION OF THE MARGIN OF SAFETY (oxidative conditions) (3 % formulation, on-head concentration 1.5 %) Absorption through the skin A = 1.35 µg/cm² Skin Area surface SAS = 580 cm2 Dermal absorption per treatment SAS x A x 0.001 = 0.783 mg Typical body weight of human = 60 kg Systemic exposure dose (SED) SAS x A x 0.001/60 = 0.013 mg/kg bw No observed adverse effect level NOAEL = 3 mg/kg bw/d (90-day, oral, rat) Bioavailability 77 %* = 2.31 mg/kg bw/d Margin of Safety adjusted NOAEL/SED = 180 * based on toxicokinetic study ref 12. 3.3.14 Discussion Physicochemical properties HC Red 18 is intended to be used as a hair dye ingredient in oxidative hair colouring products at on-head concentrations of up to 1.5%. The reported purity and impurity data on HC Red 18 cannot be accepted in the absence of the study report describing analytical methodology, validation of the method, reference standard used for the determination, etc. In addition, further identification data regarding mass spectromet","endpoint":"dermal absorption","ingredient":"HC Red No. 18","loael_value":"","noael_unit":"mg/kg bw/d","noael_value":"= 2.31","page":35,"route":"oral","species":"rat","study_id":"sccs_o_193_noael_011"}
Regulatory source developmental toxicity 50 mg/kg bw/day rat - prenatal developmental toxicity SOURCE_SUBDIR=sccs_o_193; REPORT_TITLE=OPINION ON HC Red No. 18 (В124); OPINION_NUMBER=SCCS/1569/15; COMMITTEE=Scientific Committee on Consumer Safety (SCCS); REPORT_DATE=16 March 2016; VALUE_TEXT=50; DOSE=At 50 mg/kg bw/day, relevant reproduction parameter (pre- and post-implantation loss and number of foetuses per dam) were not affected by treatment with the test substance.; EFFECT=could not be evaluated due to premature termination. At 50 mg/kg bw/day, relevant reproduction parameter (pre- and post-implantation loss and number of foetuses per dam) were not affected by treatment with the test substance. Due to premature termination of the dams at 100 and 200 mg/kg bw/day, no foetus was available for examination. At 50 mg/kg bw/day, no treatment-related effects were observed for the foetal body weight and sex ratio of the foetuses, or external abnormalities and variations. Conclusions: The NOAEL for under the conditions of this prenatal developmental toxicity range-finding study was 50 mg/kg bw/day. Ref. 9 SCCS comment The study report (Harlan study no D59271) demonstrating the stability of the test substance has not been submitted. Prenatal developmental toxicity study in rats Guideline: OECD TG 414 (2001) Species/strain: Rat, RccHanTM: WIST(SPF) Group size: 22 females/group Test substance: FPK-245 Batch: WK120919 Purity: 99.85 % Vehicle: 0.5% carboxymethylcellulose (CMC) aqueous solution Dose levels; CITATION_NUMBERS=[]; DETAILS_JSON={"cas_number":"1444596-49-9","citation":"","dose":"At 50 mg/kg bw/day, relevant reproduction parameter (pre- and post-implantation loss and number of foetuses per dam) were not affected by treatment with the test substance.","duration":"prenatal","effect":"could not be evaluated due to premature termination. At 50 mg/kg bw/day, relevant reproduction parameter (pre- and post-implantation loss and number of foetuses per dam) were not affected by treatment with the test substance. Due to premature termination of the dams at 100 and 200 mg/kg bw/day, no foetus was available for examination. At 50 mg/kg bw/day, no treatment-related effects were observed for the foetal body weight and sex ratio of the foetuses, or external abnormalities and variations. Conclusions: The NOAEL for under the conditions of this prenatal developmental toxicity range-finding study was 50 mg/kg bw/day. Ref. 9 SCCS comment The study report (Harlan study no D59271) demonstrating the stability of the test substance has not been submitted. Prenatal developmental toxicity study in rats Guideline: OECD TG 414 (2001) Species/strain: Rat, RccHanTM: WIST(SPF) Group size: 22 females/group Test substance: FPK-245 Batch: WK120919 Purity: 99.85 % Vehicle: 0.5% carboxymethylcellulose (CMC) aqueous solution Dose levels","endpoint":"developmental toxicity","ingredient":"HC Red No. 18","loael_value":"","noael_unit":"mg/kg bw/day","noael_value":"50","page":28,"route":"","species":"rat","study_id":"sccs_o_193_noael_005"}
Regulatory source developmental toxicity 50 mg/kg bw/day rat oral developmental developmental toxicity SOURCE_SUBDIR=sccs_o_193; REPORT_TITLE=OPINION ON HC Red No. 18 (В124); OPINION_NUMBER=SCCS/1569/15; COMMITTEE=Scientific Committee on Consumer Safety (SCCS); REPORT_DATE=16 March 2016; VALUE_TEXT=50; DOSE=ree and two non-pregnant animals in the control, 3, 15 and 50 mg/kg bw/day groups, respectively.; EFFECT=ree and two non-pregnant animals in the control, 3, 15 and 50 mg/kg bw/day groups, respectively. The relevant reproduction data (pre- and post-implantation loss and number of foetuses per dam) were not affected by treatment with the test substance in any group. No treatment-related effects were observed for any foetal parameters including of foetal body weight, sex ratio, external, visceral, skeletal and cartilage abnormalities, and variations or ossification and supernumerary ribs in any group. Conclusions: The NOAEL for maternal, as well as for developmental toxicity, was 50 mg/kg bw/day. Ref. 10 SCCS comment The study report (Harlan study no D59271) demonstrating the stability of the test substance has not been submitted. 3.3.9 Toxicokinetics 3.3.9.1 Toxicokinetics in laboratory animals Absorption, Distribution, Metabolism and Excretion (ADME) Following Single Percutaneous and Oral Administration in rats Guideline: OECD 417 (2010), OECD 427 (2004) Species/strain: Rats, (Crl:CD SD) Group size: 4 Male rats Test substan; CITATION_NUMBERS=[]; DETAILS_JSON={"cas_number":"1444596-49-9","citation":"","dose":"ree and two non-pregnant animals in the control, 3, 15 and 50 mg/kg bw/day groups, respectively.","duration":"developmental","effect":"ree and two non-pregnant animals in the control, 3, 15 and 50 mg/kg bw/day groups, respectively. The relevant reproduction data (pre- and post-implantation loss and number of foetuses per dam) were not affected by treatment with the test substance in any group. No treatment-related effects were observed for any foetal parameters including of foetal body weight, sex ratio, external, visceral, skeletal and cartilage abnormalities, and variations or ossification and supernumerary ribs in any group. Conclusions: The NOAEL for maternal, as well as for developmental toxicity, was 50 mg/kg bw/day. Ref. 10 SCCS comment The study report (Harlan study no D59271) demonstrating the stability of the test substance has not been submitted. 3.3.9 Toxicokinetics 3.3.9.1 Toxicokinetics in laboratory animals Absorption, Distribution, Metabolism and Excretion (ADME) Following Single Percutaneous and Oral Administration in rats Guideline: OECD 417 (2010), OECD 427 (2004) Species/strain: Rats, (Crl:CD SD) Group size: 4 Male rats Test substan","endpoint":"developmental toxicity","ingredient":"HC Red No. 18","loael_value":"","noael_unit":"mg/kg bw/day","noael_value":"50","page":29,"route":"oral","species":"rat","study_id":"sccs_o_193_noael_006"}
Regulatory source developmental toxicity 3 mg/kg bw/day rat oral 14-day developmental toxicity SOURCE_SUBDIR=sccs_o_193; REPORT_TITLE=OPINION ON HC Red No. 18 (В124); OPINION_NUMBER=SCCS/1569/15; COMMITTEE=Scientific Committee on Consumer Safety (SCCS); REPORT_DATE=16 March 2016; VALUE_TEXT=3; DOSE=e mortalities in the 14-day dose range-finding rat study from 300(200) mg/kg bw/day, HC Red 18 is considered to possess a moderate acute toxic potential following oral administration.; EFFECT=e mortalities in the 14-day dose range-finding rat study from 300(200) mg/kg bw/day, HC Red 18 is considered to possess a moderate acute toxic potential following oral administration. Daily administration of HC Red 18 by oral gavage to Sprague Dawley rats at a dose level of 30 mg/kg bw/day and higher for 90 days resulted in atrophy, degeneration and/or regeneration of muscle fibre in the femoral muscle. At 150/75/50 mg/kg bw/day, severe signs of systemic toxicity, including mortality/moribundity were observed. The NOAEL of 3 mg/kg bw/day is used for the MOS calculation. In the developmental toxicity study in rats, daily administration by oral gavage to pregnant female Wistar rats at a dose level of 50 mg/kg bw/day during gestation days 6 to 20 resulted in minimal maternal toxicity. The NOAEL for maternal and developmental toxicity is considered to be 50 mg/kg bw/day. Neither malformations nor variations occurred at the highest dose level of 50 mg/kg bw/day. Irritation/sensitisation The skin irritation potential of HC Red No. 18; CITATION_NUMBERS=[]; DETAILS_JSON={"cas_number":"1444596-49-9","citation":"","dose":"e mortalities in the 14-day dose range-finding rat study from 300(200) mg/kg bw/day, HC Red 18 is considered to possess a moderate acute toxic potential following oral administration.","duration":"14-day","effect":"e mortalities in the 14-day dose range-finding rat study from 300(200) mg/kg bw/day, HC Red 18 is considered to possess a moderate acute toxic potential following oral administration. Daily administration of HC Red 18 by oral gavage to Sprague Dawley rats at a dose level of 30 mg/kg bw/day and higher for 90 days resulted in atrophy, degeneration and/or regeneration of muscle fibre in the femoral muscle. At 150/75/50 mg/kg bw/day, severe signs of systemic toxicity, including mortality/moribundity were observed. The NOAEL of 3 mg/kg bw/day is used for the MOS calculation. In the developmental toxicity study in rats, daily administration by oral gavage to pregnant female Wistar rats at a dose level of 50 mg/kg bw/day during gestation days 6 to 20 resulted in minimal maternal toxicity. The NOAEL for maternal and developmental toxicity is considered to be 50 mg/kg bw/day. Neither malformations nor variations occurred at the highest dose level of 50 mg/kg bw/day. Irritation/sensitisation The skin irritation potential of HC Red No. 18","endpoint":"developmental toxicity","ingredient":"HC Red No. 18","loael_value":"","noael_unit":"mg/kg bw/day","noael_value":"3","page":36,"route":"oral","species":"rat","study_id":"sccs_o_193_noael_012"}
Regulatory source developmental toxicity 50 mg/kg bw/day rat oral 90 days developmental toxicity SOURCE_SUBDIR=sccs_o_193; REPORT_TITLE=OPINION ON HC Red No. 18 (В124); OPINION_NUMBER=SCCS/1569/15; COMMITTEE=Scientific Committee on Consumer Safety (SCCS); REPORT_DATE=16 March 2016; VALUE_TEXT=50; DOSE=mg/kg bw/day and higher for 90 days resulted in atrophy, degeneration and/or regeneration of muscle fibre in the femoral muscle.; EFFECT=mg/kg bw/day and higher for 90 days resulted in atrophy, degeneration and/or regeneration of muscle fibre in the femoral muscle. At 150/75/50 mg/kg bw/day, severe signs of systemic toxicity, including mortality/moribundity were observed. The NOAEL of 3 mg/kg bw/day is used for the MOS calculation. In the developmental toxicity study in rats, daily administration by oral gavage to pregnant female Wistar rats at a dose level of 50 mg/kg bw/day during gestation days 6 to 20 resulted in minimal maternal toxicity. The NOAEL for maternal and developmental toxicity is considered to be 50 mg/kg bw/day. Neither malformations nor variations occurred at the highest dose level of 50 mg/kg bw/day. Irritation/sensitisation The skin irritation potential of HC Red No. 18 as neat substance has been tested using an in vitro skin irritation test method according to OECD TG 439 (July 2010). As red colouring of the tissues by the test item might have occurred, interference with the MTT cell viability endpoint is expected. leading to false estimate; CITATION_NUMBERS=[]; DETAILS_JSON={"cas_number":"1444596-49-9","citation":"","dose":"mg/kg bw/day and higher for 90 days resulted in atrophy, degeneration and/or regeneration of muscle fibre in the femoral muscle.","duration":"90 days","effect":"mg/kg bw/day and higher for 90 days resulted in atrophy, degeneration and/or regeneration of muscle fibre in the femoral muscle. At 150/75/50 mg/kg bw/day, severe signs of systemic toxicity, including mortality/moribundity were observed. The NOAEL of 3 mg/kg bw/day is used for the MOS calculation. In the developmental toxicity study in rats, daily administration by oral gavage to pregnant female Wistar rats at a dose level of 50 mg/kg bw/day during gestation days 6 to 20 resulted in minimal maternal toxicity. The NOAEL for maternal and developmental toxicity is considered to be 50 mg/kg bw/day. Neither malformations nor variations occurred at the highest dose level of 50 mg/kg bw/day. Irritation/sensitisation The skin irritation potential of HC Red No. 18 as neat substance has been tested using an in vitro skin irritation test method according to OECD TG 439 (July 2010). As red colouring of the tissues by the test item might have occurred, interference with the MTT cell viability endpoint is expected. leading to false estimate","endpoint":"developmental toxicity","ingredient":"HC Red No. 18","loael_value":"","noael_unit":"mg/kg bw/day","noael_value":"50","page":36,"route":"oral","species":"rat","study_id":"sccs_o_193_noael_013"}
Regulatory source genotoxicity 3 mg/kg bw/day rat oral 91 days genotoxicity SOURCE_SUBDIR=sccs_o_193; REPORT_TITLE=OPINION ON HC Red No. 18 (В124); OPINION_NUMBER=SCCS/1569/15; COMMITTEE=Scientific Committee on Consumer Safety (SCCS); REPORT_DATE=16 March 2016; VALUE_TEXT=3; DOSE=Other observed histopathological changes were considered by the study report authors to be secondary changes related to poor health conditions or death, or to be common spontaneous changes found in normal rats, or the lack of dose- relation.; EFFECT=tion of muscle fibre were not observed in any animals. In the females that died or were sacrificed in moribundity, atrophy, degeneration and/or regeneration of muscle fibre were observed as in the scheduled sacrifice animals. Their grades were minimal to mild. Other observed histopathological changes were considered by the study report authors to be secondary changes related to poor health conditions or death, or to be common spontaneous changes found in normal rats, or the lack of dose- relation. Conclusion The NOAEL of FPK-245 was shown to be 3 mg/kg bw/day in male and female rats after continuous oral administration for 91 days. Ref. 15 SCCS comment The SCCS agrees with the NOAEL of 3 mg/kg bw/day; this NOAEL is used for the MOS calculation. 3.3.5.3 Chronic (> 12 months) toxicity No data 3.3.6 Mutagenicity / Genotoxicity 3.3.6.1 Mutagenicity / Genotoxicity in vitro Bacterial Reverse Mutation Test Guideline: OECD 471, Commission Regulation (EC) 440/2008, B.13/14, Japanese Guidelines Species/strain: Salmonella typhi; CITATION_NUMBERS=[]; DETAILS_JSON={"cas_number":"1444596-49-9","citation":"","dose":"Other observed histopathological changes were considered by the study report authors to be secondary changes related to poor health conditions or death, or to be common spontaneous changes found in normal rats, or the lack of dose- relation.","duration":"91 days","effect":"tion of muscle fibre were not observed in any animals. In the females that died or were sacrificed in moribundity, atrophy, degeneration and/or regeneration of muscle fibre were observed as in the scheduled sacrifice animals. Their grades were minimal to mild. Other observed histopathological changes were considered by the study report authors to be secondary changes related to poor health conditions or death, or to be common spontaneous changes found in normal rats, or the lack of dose- relation. Conclusion The NOAEL of FPK-245 was shown to be 3 mg/kg bw/day in male and female rats after continuous oral administration for 91 days. Ref. 15 SCCS comment The SCCS agrees with the NOAEL of 3 mg/kg bw/day; this NOAEL is used for the MOS calculation. 3.3.5.3 Chronic (> 12 months) toxicity No data 3.3.6 Mutagenicity / Genotoxicity 3.3.6.1 Mutagenicity / Genotoxicity in vitro Bacterial Reverse Mutation Test Guideline: OECD 471, Commission Regulation (EC) 440/2008, B.13/14, Japanese Guidelines Species/strain: Salmonella typhi","endpoint":"genotoxicity","ingredient":"HC Red No. 18","loael_value":"","noael_unit":"mg/kg bw/day","noael_value":"3","page":22,"route":"oral","species":"rat","study_id":"sccs_o_193_noael_002"}
Regulatory source genotoxicity 3 mg/kg bw/day rat oral 91 days genotoxicity SOURCE_SUBDIR=sccs_o_193; REPORT_TITLE=OPINION ON HC Red No. 18 (В124); OPINION_NUMBER=SCCS/1569/15; COMMITTEE=Scientific Committee on Consumer Safety (SCCS); REPORT_DATE=16 March 2016; VALUE_TEXT=3; DOSE=Other observed histopathological changes were considered by the study report authors to be secondary changes related to poor health conditions or death, or to be common spontaneous changes found in normal rats, or the lack of dose- relation.; EFFECT=fibre were observed as in the scheduled sacrifice animals. Their grades were minimal to mild. Other observed histopathological changes were considered by the study report authors to be secondary changes related to poor health conditions or death, or to be common spontaneous changes found in normal rats, or the lack of dose- relation. Conclusion The NOAEL of FPK-245 was shown to be 3 mg/kg bw/day in male and female rats after continuous oral administration for 91 days. Ref. 15 SCCS comment The SCCS agrees with the NOAEL of 3 mg/kg bw/day; this NOAEL is used for the MOS calculation. 3.3.5.3 Chronic (> 12 months) toxicity No data 3.3.6 Mutagenicity / Genotoxicity 3.3.6.1 Mutagenicity / Genotoxicity in vitro Bacterial Reverse Mutation Test Guideline: OECD 471, Commission Regulation (EC) 440/2008, B.13/14, Japanese Guidelines Species/strain: Salmonella typhimurium strains TA 1535, TA 1537, TA 98, TA 100 and the Escherichia coli strain WP2 uvrA Replicates: Triplicate plates, 2 independent tests Test substance: FPK-245 Batch; CITATION_NUMBERS=[]; DETAILS_JSON={"cas_number":"1444596-49-9","citation":"","dose":"Other observed histopathological changes were considered by the study report authors to be secondary changes related to poor health conditions or death, or to be common spontaneous changes found in normal rats, or the lack of dose- relation.","duration":"91 days","effect":"fibre were observed as in the scheduled sacrifice animals. Their grades were minimal to mild. Other observed histopathological changes were considered by the study report authors to be secondary changes related to poor health conditions or death, or to be common spontaneous changes found in normal rats, or the lack of dose- relation. Conclusion The NOAEL of FPK-245 was shown to be 3 mg/kg bw/day in male and female rats after continuous oral administration for 91 days. Ref. 15 SCCS comment The SCCS agrees with the NOAEL of 3 mg/kg bw/day; this NOAEL is used for the MOS calculation. 3.3.5.3 Chronic (> 12 months) toxicity No data 3.3.6 Mutagenicity / Genotoxicity 3.3.6.1 Mutagenicity / Genotoxicity in vitro Bacterial Reverse Mutation Test Guideline: OECD 471, Commission Regulation (EC) 440/2008, B.13/14, Japanese Guidelines Species/strain: Salmonella typhimurium strains TA 1535, TA 1537, TA 98, TA 100 and the Escherichia coli strain WP2 uvrA Replicates: Triplicate plates, 2 independent tests Test substance: FPK-245 Batch","endpoint":"genotoxicity","ingredient":"HC Red No. 18","loael_value":"","noael_unit":"mg/kg bw/day","noael_value":"3","page":22,"route":"oral","species":"rat","study_id":"sccs_o_193_noael_003"}
Regulatory source genotoxicity 3 mg/kg bw/day rat oral 91 days genotoxicity SOURCE_SUBDIR=sccs_o_193; REPORT_TITLE=OPINION ON HC Red No. 18 (В124); OPINION_NUMBER=SCCS/1569/15; COMMITTEE=Scientific Committee on Consumer Safety (SCCS); REPORT_DATE=16 March 2016; VALUE_TEXT=3; DOSE=Other observed histopathological changes were considered by the study report authors to be secondary changes related to poor health conditions or death, or to be common spontaneous changes found in normal rats, or the lack of dose- relation.; EFFECT=scheduled sacrifice animals. Their grades were minimal to mild. Other observed histopathological changes were considered by the study report authors to be secondary changes related to poor health conditions or death, or to be common spontaneous changes found in normal rats, or the lack of dose- relation. Conclusion The NOAEL of FPK-245 was shown to be 3 mg/kg bw/day in male and female rats after continuous oral administration for 91 days. Ref. 15 SCCS comment The SCCS agrees with the NOAEL of 3 mg/kg bw/day; this NOAEL is used for the MOS calculation. 3.3.5.3 Chronic (> 12 months) toxicity No data 3.3.6 Mutagenicity / Genotoxicity 3.3.6.1 Mutagenicity / Genotoxicity in vitro Bacterial Reverse Mutation Test Guideline: OECD 471, Commission Regulation (EC) 440/2008, B.13/14, Japanese Guidelines Species/strain: Salmonella typhimurium strains TA 1535, TA 1537, TA 98, TA 100 and the Escherichia coli strain WP2 uvrA Replicates: Triplicate plates, 2 independent tests Test substance: FPK-245 Batch: 06041404 Purity: 99.88% So; CITATION_NUMBERS=[]; DETAILS_JSON={"cas_number":"1444596-49-9","citation":"","dose":"Other observed histopathological changes were considered by the study report authors to be secondary changes related to poor health conditions or death, or to be common spontaneous changes found in normal rats, or the lack of dose- relation.","duration":"91 days","effect":"scheduled sacrifice animals. Their grades were minimal to mild. Other observed histopathological changes were considered by the study report authors to be secondary changes related to poor health conditions or death, or to be common spontaneous changes found in normal rats, or the lack of dose- relation. Conclusion The NOAEL of FPK-245 was shown to be 3 mg/kg bw/day in male and female rats after continuous oral administration for 91 days. Ref. 15 SCCS comment The SCCS agrees with the NOAEL of 3 mg/kg bw/day; this NOAEL is used for the MOS calculation. 3.3.5.3 Chronic (> 12 months) toxicity No data 3.3.6 Mutagenicity / Genotoxicity 3.3.6.1 Mutagenicity / Genotoxicity in vitro Bacterial Reverse Mutation Test Guideline: OECD 471, Commission Regulation (EC) 440/2008, B.13/14, Japanese Guidelines Species/strain: Salmonella typhimurium strains TA 1535, TA 1537, TA 98, TA 100 and the Escherichia coli strain WP2 uvrA Replicates: Triplicate plates, 2 independent tests Test substance: FPK-245 Batch: 06041404 Purity: 99.88% So","endpoint":"genotoxicity","ingredient":"HC Red No. 18","loael_value":"","noael_unit":"mg/kg bw/day","noael_value":"3","page":22,"route":"oral","species":"rat","study_id":"sccs_o_193_noael_004"}
Regulatory source irritation 77 % rat oral - irritation SOURCE_SUBDIR=sccs_o_193; REPORT_TITLE=OPINION ON HC Red No. 18 (В124); OPINION_NUMBER=SCCS/1569/15; COMMITTEE=Scientific Committee on Consumer Safety (SCCS); REPORT_DATE=16 March 2016; VALUE_TEXT=77; DOSE=ely 65 % of the dose from the GI tract.; EFFECT=ely 65 % of the dose from the GI tract. In bile-duct cannulated rats, approximately 48 %, 29 % and 24 % of the dose was excreted in the bile, urine and faeces, respectively, indicating an oral absorption of up to approximately 77 % of the dose from the GI tract (sum of dose excreted in the bile and the urine). Under the conditions of this toxicokinetic study, an oral absorption of 77% is considered based on the results from the bile-duct cannulated rats. The oral absorption of 77% is used for the correction of the NOAEL for the MoS calculation. 3.3.9.2 Toxicokinetics in humans / 3.3.10 Photo-induced toxicity 3.3.10.1 Phototoxicity / photo-irritation and photosensitisation No data 3.3.10.2 Photomutagenicity / photoclastogenicity No data 3.3.11 Human data No data; CITATION_NUMBERS=[]; DETAILS_JSON={"cas_number":"1444596-49-9","citation":"","dose":"ely 65 % of the dose from the GI tract.","duration":"","effect":"ely 65 % of the dose from the GI tract. In bile-duct cannulated rats, approximately 48 %, 29 % and 24 % of the dose was excreted in the bile, urine and faeces, respectively, indicating an oral absorption of up to approximately 77 % of the dose from the GI tract (sum of dose excreted in the bile and the urine). Under the conditions of this toxicokinetic study, an oral absorption of 77% is considered based on the results from the bile-duct cannulated rats. The oral absorption of 77% is used for the correction of the NOAEL for the MoS calculation. 3.3.9.2 Toxicokinetics in humans / 3.3.10 Photo-induced toxicity 3.3.10.1 Phototoxicity / photo-irritation and photosensitisation No data 3.3.10.2 Photomutagenicity / photoclastogenicity No data 3.3.11 Human data No data","endpoint":"irritation","ingredient":"HC Red No. 18","loael_value":"","noael_unit":"%","noael_value":"77","page":32,"route":"oral","species":"rat","study_id":"sccs_o_193_noael_007"}
Regulatory source repeated dose toxicity 100 mg/kg bw/day rat oral Sub-chronic repeated dose toxicity SOURCE_SUBDIR=sccs_o_193; REPORT_TITLE=OPINION ON HC Red No. 18 (В124); OPINION_NUMBER=SCCS/1569/15; COMMITTEE=Scientific Committee on Consumer Safety (SCCS); REPORT_DATE=16 March 2016; VALUE_TEXT=100; DOSE=A statistically significant increase in relative liver weights was noted in males at 300(200) mg/kg bw/day and in females from 100 mg/kg bw/day.; EFFECT=n was decreased in the same animals. Several changes related to the test substance or severely affected health conditions were noted in clinical chemistry. A statistically significant increase in relative liver weights was noted in males at 300(200) mg/kg bw/day and in females from 100 mg/kg bw/day. A statistically significant increase in relative thyroids weights was observed in females at 300(200) mg/kg bw/day. At necropsy, a small spleen was noted in one surviving male at 300(200) mg/kg bw/day). Conclusion The NOAEL was 100 mg/kg bw/day in males and 30 mg/kg bw/day in females under the conditions of this study. Ref. 14 3.3.5.2 Sub-chronic (90 days) toxicity (oral) Guideline: OECD TG 408 (1997) Species/strain: Rats/ Crl:CD(SD) Group size: 15/sex/group (control and high-dose groups), 10/sex/group (other groups) Test substance: FPK-254 Batch: WK120919 Purity: 99.85% Vehicle: 0.5% Methylcellulose solution Dose levels: 0, 3, 30, and 150(75/50) mg/kg bw/day Dose volume: 10 ml/kg bw/day; CITATION_NUMBERS=[]; DETAILS_JSON={"cas_number":"1444596-49-9","citation":"","dose":"A statistically significant increase in relative liver weights was noted in males at 300(200) mg/kg bw/day and in females from 100 mg/kg bw/day.","duration":"Sub-chronic","effect":"n was decreased in the same animals. Several changes related to the test substance or severely affected health conditions were noted in clinical chemistry. A statistically significant increase in relative liver weights was noted in males at 300(200) mg/kg bw/day and in females from 100 mg/kg bw/day. A statistically significant increase in relative thyroids weights was observed in females at 300(200) mg/kg bw/day. At necropsy, a small spleen was noted in one surviving male at 300(200) mg/kg bw/day). Conclusion The NOAEL was 100 mg/kg bw/day in males and 30 mg/kg bw/day in females under the conditions of this study. Ref. 14 3.3.5.2 Sub-chronic (90 days) toxicity (oral) Guideline: OECD TG 408 (1997) Species/strain: Rats/ Crl:CD(SD) Group size: 15/sex/group (control and high-dose groups), 10/sex/group (other groups) Test substance: FPK-254 Batch: WK120919 Purity: 99.85% Vehicle: 0.5% Methylcellulose solution Dose levels: 0, 3, 30, and 150(75/50) mg/kg bw/day Dose volume: 10 ml/kg bw/day","endpoint":"repeated dose toxicity","ingredient":"HC Red No. 18","loael_value":"","noael_unit":"mg/kg bw/day","noael_value":"100","page":19,"route":"oral","species":"rat","study_id":"sccs_o_193_noael_001"}
Regulatory source repeated dose toxicity 3 mg/kg/day rat - 90-day repeated dose toxicity SOURCE_SUBDIR=sccs_o_193; REPORT_TITLE=OPINION ON HC Red No. 18 (В124); OPINION_NUMBER=SCCS/1569/15; COMMITTEE=Scientific Committee on Consumer Safety (SCCS); REPORT_DATE=16 March 2016; VALUE_TEXT=3; DOSE=Based on the results from the 90-day repeated dose toxicity study, the NOAEL for FPK-245 is 3 mg/kg/day.” 3.3.13 Safety evaluation (including calculation of the MoS) FPK-245 is only intended as a hair dye ingredient in oxidative hair colouring products at on- head concentrations of up to 1.5%.; EFFECT=een performed to review the toxicity data related to FPK-245 and to assess the toxicological relevance of treatment-associated changes. The conclusions of the expert in relation to hepatocarcinogenicity are as follows: “The lack of a significant increase in GST-P foci in the livers of the toxicity study rats as well as a negative GST-P medium term carcinogenicity assay provide further support for lack of hepatocarcinogenic potential of FPK-245. Based on the results from the 90-day repeated dose toxicity study, the NOAEL for FPK-245 is 3 mg/kg/day.” 3.3.13 Safety evaluation (including calculation of the MoS) FPK-245 is only intended as a hair dye ingredient in oxidative hair colouring products at on- head concentrations of up to 1.5%. Therefore, the value of 0.973 μg/cm² obtained under oxidative conditions will be used for risk assessment and Margin of Safety (MoS) calculation. CALCULATION OF THE MARGIN OF SAFETY (oxidative conditions) (3 % formulation, on-head concentration 1.5 %) Absorption through the skin A = 1.35 µg/cm; CITATION_NUMBERS=[]; DETAILS_JSON={"cas_number":"1444596-49-9","citation":"","dose":"Based on the results from the 90-day repeated dose toxicity study, the NOAEL for FPK-245 is 3 mg/kg/day.” 3.3.13 Safety evaluation (including calculation of the MoS) FPK-245 is only intended as a hair dye ingredient in oxidative hair colouring products at on- head concentrations of up to 1.5%.","duration":"90-day","effect":"een performed to review the toxicity data related to FPK-245 and to assess the toxicological relevance of treatment-associated changes. The conclusions of the expert in relation to hepatocarcinogenicity are as follows: “The lack of a significant increase in GST-P foci in the livers of the toxicity study rats as well as a negative GST-P medium term carcinogenicity assay provide further support for lack of hepatocarcinogenic potential of FPK-245. Based on the results from the 90-day repeated dose toxicity study, the NOAEL for FPK-245 is 3 mg/kg/day.” 3.3.13 Safety evaluation (including calculation of the MoS) FPK-245 is only intended as a hair dye ingredient in oxidative hair colouring products at on- head concentrations of up to 1.5%. Therefore, the value of 0.973 μg/cm² obtained under oxidative conditions will be used for risk assessment and Margin of Safety (MoS) calculation. CALCULATION OF THE MARGIN OF SAFETY (oxidative conditions) (3 % formulation, on-head concentration 1.5 %) Absorption through the skin A = 1.35 µg/cm","endpoint":"repeated dose toxicity","ingredient":"HC Red No. 18","loael_value":"","noael_unit":"mg/kg/day","noael_value":"3","page":35,"route":"","species":"rat","study_id":"sccs_o_193_noael_008"}
Regulatory source repeated dose toxicity 3 mg/kg/day rat oral 90-day repeated dose toxicity SOURCE_SUBDIR=sccs_o_193; REPORT_TITLE=OPINION ON HC Red No. 18 (В124); OPINION_NUMBER=SCCS/1569/15; COMMITTEE=Scientific Committee on Consumer Safety (SCCS); REPORT_DATE=16 March 2016; VALUE_TEXT=3; DOSE=Based on the results from the 90-day repeated dose toxicity study, the NOAEL for FPK-245 is 3 mg/kg/day.” Toxicokinetics Under the conditions of the in vivo toxicokinetic study, an oral absorption of 77% is considered based on the results from the bile-duct cannulated rats showing an excretion of about 48% and 29% of the dose in bile and urine,...; EFFECT=rformed to review the toxicity data related to HC Red No. 18 and to assess the toxicological relevance of treatment-associated changes. The conclusions of the expert in relation to hepatocarcinogenicity are as follows: “The lack of a significant increase in GST-P foci in the livers of the toxicity study rats as well as a negative GST-P medium term carcinogenicity assay provide further support for lack of hepatocarcinogenic potential of FPK-245. Based on the results from the 90-day repeated dose toxicity study, the NOAEL for FPK-245 is 3 mg/kg/day.” Toxicokinetics Under the conditions of the in vivo toxicokinetic study, an oral absorption of 77% is considered based on the results from the bile-duct cannulated rats showing an excretion of about 48% and 29% of the dose in bile and urine, respectively. An oral absorption of 77% is used for the correction of the NOAEL for the MoS calculation. Human data No data were submitted.; CITATION_NUMBERS=[]; DETAILS_JSON={"cas_number":"1444596-49-9","citation":"","dose":"Based on the results from the 90-day repeated dose toxicity study, the NOAEL for FPK-245 is 3 mg/kg/day.” Toxicokinetics Under the conditions of the in vivo toxicokinetic study, an oral absorption of 77% is considered based on the results from the bile-duct cannulated rats showing an excretion of about 48% and 29% of the dose in bile and urine,...","duration":"90-day","effect":"rformed to review the toxicity data related to HC Red No. 18 and to assess the toxicological relevance of treatment-associated changes. The conclusions of the expert in relation to hepatocarcinogenicity are as follows: “The lack of a significant increase in GST-P foci in the livers of the toxicity study rats as well as a negative GST-P medium term carcinogenicity assay provide further support for lack of hepatocarcinogenic potential of FPK-245. Based on the results from the 90-day repeated dose toxicity study, the NOAEL for FPK-245 is 3 mg/kg/day.” Toxicokinetics Under the conditions of the in vivo toxicokinetic study, an oral absorption of 77% is considered based on the results from the bile-duct cannulated rats showing an excretion of about 48% and 29% of the dose in bile and urine, respectively. An oral absorption of 77% is used for the correction of the NOAEL for the MoS calculation. Human data No data were submitted.","endpoint":"repeated dose toxicity","ingredient":"HC Red No. 18","loael_value":"","noael_unit":"mg/kg/day","noael_value":"3","page":37,"route":"oral","species":"rat","study_id":"sccs_o_193_noael_014"}
Regulatory source repeated dose toxicity 77 % rat oral 90-day repeated dose toxicity SOURCE_SUBDIR=sccs_o_193; REPORT_TITLE=OPINION ON HC Red No. 18 (В124); OPINION_NUMBER=SCCS/1569/15; COMMITTEE=Scientific Committee on Consumer Safety (SCCS); REPORT_DATE=16 March 2016; VALUE_TEXT=77; DOSE=Based on the results from the 90-day repeated dose toxicity study, the NOAEL for FPK-245 is 3 mg/kg/day.” Toxicokinetics Under the conditions of the in vivo toxicokinetic study, an oral absorption of 77% is considered based on the results from the bile-duct cannulated rats showing an excretion of about 48% and 29% of the dose in bile and urine,...; EFFECT=rcinogenicity assay provide further support for lack of hepatocarcinogenic potential of FPK-245. Based on the results from the 90-day repeated dose toxicity study, the NOAEL for FPK-245 is 3 mg/kg/day.” Toxicokinetics Under the conditions of the in vivo toxicokinetic study, an oral absorption of 77% is considered based on the results from the bile-duct cannulated rats showing an excretion of about 48% and 29% of the dose in bile and urine, respectively. An oral absorption of 77% is used for the correction of the NOAEL for the MoS calculation. Human data No data were submitted.; CITATION_NUMBERS=[]; DETAILS_JSON={"cas_number":"1444596-49-9","citation":"","dose":"Based on the results from the 90-day repeated dose toxicity study, the NOAEL for FPK-245 is 3 mg/kg/day.” Toxicokinetics Under the conditions of the in vivo toxicokinetic study, an oral absorption of 77% is considered based on the results from the bile-duct cannulated rats showing an excretion of about 48% and 29% of the dose in bile and urine,...","duration":"90-day","effect":"rcinogenicity assay provide further support for lack of hepatocarcinogenic potential of FPK-245. Based on the results from the 90-day repeated dose toxicity study, the NOAEL for FPK-245 is 3 mg/kg/day.” Toxicokinetics Under the conditions of the in vivo toxicokinetic study, an oral absorption of 77% is considered based on the results from the bile-duct cannulated rats showing an excretion of about 48% and 29% of the dose in bile and urine, respectively. An oral absorption of 77% is used for the correction of the NOAEL for the MoS calculation. Human data No data were submitted.","endpoint":"repeated dose toxicity","ingredient":"HC Red No. 18","loael_value":"","noael_unit":"%","noael_value":"77","page":37,"route":"oral","species":"rat","study_id":"sccs_o_193_noael_015"}