NOAEL Studies Cosmetic Ingredient

HC Blue No. 12 NOAEL Studies

INCI: HC BLUE NO. 12

CAS: 132885-85-9

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_vision_codex 32 endpoints
Source Endpoint Type Value Unit Species Route Duration Study Type Reference
SCCS_vision_codex NOAEL =30 mg/kg bw rat oral 90-day irritation {"dose":"In the 90-day study with rats, 30 mg/kg bw was considered to be the NOAEL.","effect":"e, earlier called Nitroblau, was submitted in March 1992 by COLIPA1, 2. The Scientific Committee on Cosmetology (SCC) adopted at its 53rd plenary meeting on 25 June 1993 an opinion (SPC/1077/93) with the final conclusion that: “Nitroblau was found moderately toxic in the acute oral toxicity test and slightly toxic after dermal administration to rabbits. Nitroblau showed no signs of irritation. The sensitization test was carried out inadequately. In the 90-day study with rats, 30 mg/kg bw was considered to be the NOAEL. In the teratogenicity study, no irreversible structural changes were observed in the foetuses of the rat, after administration of 140 mg/kg bw. Nitroblau is not genotoxic. The cutaneous absorption was 1% of the administered 14C for the hair dyeing formulation. For normal use of hair dye, the following calculation can be made: 750 mg nitroblau comes in contact with the human skin in permanent hair dye condition (based on a usage volume of 100 ml containing 0.75% nitroblau). With a maximal penetration of 1%, this r","page":5,"pdf":"sccp_o_117.pdf","row_type":"noael_study","study_id":"sccp_o_117_noael_001"}
SCCS_vision_codex NOAEL =140 mg/kg bw rat dermal 90-day dermal absorption {"dose":"With a penetration of 1%; this results in a dermal absorption of 5.25 mg per treatment, which is 0.0875 mg/kg bw So a margin of safety of 240 can be calculated between the figure for human exposure to oxidative hair dye and the no adverse effect level found in rats in the 90-day study (limited study, only 1 dose tested).","effect":"With a penetration of 1%; this results in a dermal absorption of 5.25 mg per treatment, which is 0.0875 mg/kg bw So a margin of safety of 240 can be calculated between the figure for human exposure to oxidative hair dye and the no adverse effect level found in rats in the 90-day study (limited study, only 1 dose tested). It should be noted that no effects were observed in the teratogenicity study at 140 mg/kg bw. For the semi-permanent hair dye a safety margin of 343 can be calculated. It should be noted that the NOAEL stems from a daily exposure for 90 days, whereas human exposure to permanent hair dye is unlikely to be more frequent than once a month and human exposure to semi-permanent hair dye is unlikely to be more than once a week.” Submission II for HC Blue n° 12 was submitted in December 1993 by COLIPA². The Scientific Committee on Cosmetic products and Non-Food Products intended for Consumers (SCCNFP) adopted at its plenary meeting on 23 June 1999 an opinion (SCCNFP/0140/99) with the conclusion that: “The SCCNFP is o","page":5,"pdf":"sccp_o_117.pdf","row_type":"noael_study","study_id":"sccp_o_117_noael_002"}
SCCS_vision_codex NOAEL =316 mg/kg bw/d - - 28 day NOAEL study {"citation":"Ref.: 21","dose":"igh dose females also the coagulation time was raised.","effect":"igh dose females also the coagulation time was raised. Clinical chemistry showed changes in uric acid (lowered at high dose, both sexes) and bilirubin (raised at high dose, both sexes). Absolute and relative spleen weights were increased at the high dose but significance was reached only in males. Also in the high dose group liver weight was increased (females only). At the high dose with both sexes in the spleen lymphoid depletion and congestion as well as induction of haematopoesis were observed. Conclusion The NOAEL of the 28 day toxicity study is 316 mg/kg bw/d. Ref.: 21","page":18,"pdf":"sccp_o_117.pdf","row_type":"noael_study","study_id":"sccp_o_117_noael_003"}
SCCS_vision_codex NOAEL =60 mg/kg bw/d rat oral 13 weeks NOAEL study {"citation":"Ref.: 22, 23 Rat Study 2 Guideline: / Species/strain: Wistar rats Bor","dose":"Feed and water consumption and body weight gain were in the physiological range and no dose related changes were noted.","effect":"ctivity measurement and ophthalmoscopic examination did not show a difference between control and test groups. Feed and water consumption and body weight gain were in the physiological range and no dose related changes were noted. Also neither haematology, biochemistry or urinalysis revealed test substance related changes. The histomorphological investigation revealed no substance-related alterations. Conclusion Under the conditions of the study the highest dose tested dose of 60 mg/kg bw/d was found as being the NOAEL dose. However, only a limited number of animals (5 per sex and dose) were analysed histopathologically. Ref.: 22, 23 Rat Study 2 Guideline: / Species/strain: Wistar rats Bor.Wis.W. (SPF) Group size: 12 per sex Test substance: Nitroblau hydrochloride in distilled water Batch: L4/154 Purity: 93.2 % (HPLC) Dose: 30 mg/kg bw/d Route: oral, gavage Exposure: 13 weeks GLP: in compliance The test substance was administered at 30 mg/kg bw/d to 12 male and 12 female Wistar rats by oral gavage for 13 weeks. No control g","page":19,"pdf":"sccp_o_117.pdf","row_type":"noael_study","study_id":"sccp_o_117_noael_004"}
SCCS_vision_codex NOAEL =140 mg/kg bw/d human - developmental developmental toxicity {"citation":"Ref.: 34 Comment The highest dose of 140 mg/kg bw is too low for hazard assessment","dose":"Results With the exception of violet staining of urine (all treated animals) and fur, paw and tail (high dose group) no clinical signs were noted.","effect":"mperfections and the remainder was subjected to skeletal examination. Results With the exception of violet staining of urine (all treated animals) and fur, paw and tail (high dose group) no clinical signs were noted. Food consumption and body weight changes of the dams were not significantly different from controls. Foetal weight, sex ratio, placental weight, number of resorptions and corpora lutea were not influenced by treatment. Examination of skeleton and viscera revealed no relevant findings. Conclusion The NOAEL of maternal and developmental toxicity in this study is 140 mg/kg bw/d. Ref.: 34 Comment The highest dose of 140 mg/kg bw is too low for hazard assessment. For this, the highest dose used should be 1000 mg/kg bw and should induce toxicity. 3.3.9. Toxicokinetics 3.3.9.1. Toxicokinetics in vitro Bioavailability across intestinal barrier in TC-7 (human intestinal epithelial) cells Guideline: / Cells: Human intestinal epithelial cell line TC-7 Test substance: HC Blue n° 12 Batch: 29/30 Purity: 93.9 area% (HPLC) T","page":27,"pdf":"sccp_o_117.pdf","row_type":"noael_study","study_id":"sccp_o_117_noael_006"}
SCCS_vision_codex NOAEL =0.253 mg/kg rat oral 13-week dermal absorption {"dose":"Safety evaluation (including calculation of the MoS) CALCULATION OF THE MARGIN OF SAFETY (HC Blue n° 12) (oxidative and non-oxidative) Maximum absorption through the skin A (µg/cm2) = 21.7 µg/cm² Skin Area surface SAS (cm2) = 700 cm2 Dermal absorption per treatment SAS x A x 0.001 = 15.19 mg Typical body weight of human = 60 kg Systemic exposure...","effect":"icity No data submitted 3.3.11. Human data No data submitted 3.3.12. Special investigations No data submitted 3.3.13. Safety evaluation (including calculation of the MoS) CALCULATION OF THE MARGIN OF SAFETY (HC Blue n° 12) (oxidative and non-oxidative) Maximum absorption through the skin A (µg/cm2) = 21.7 µg/cm² Skin Area surface SAS (cm2) = 700 cm2 Dermal absorption per treatment SAS x A x 0.001 = 15.19 mg Typical body weight of human = 60 kg Systemic exposure dose (SED) SAS x A x 0.001/60 = 0.253 mg/kg No observed adverse effect level NOAEL = 60 mg/kg bw (13-week, oral, rat) Margin of Safety NOAEL / SED = 237 3.3.14. Discussion Physico-chemical properties HC Blue n° 12 is used as a non-reactive hair colouring agent (\"Direct Dye\") in semi- permanent hair dye formulations at a maximum on-head concentration of 1.5 %, as well as a non-reactive hair colouring agent (\"Direct Dye\") in oxidative hair dye formulations at a maximum on-head concentration of 0.75 %. HC Blue n° 12 is both a secondary and a tertiary amine and thus is prone to nitrosation","page":29,"pdf":"sccp_o_117.pdf","row_type":"noael_study","study_id":"sccp_o_117_noael_007"}
SCCS_vision_codex NOAEL =60 mg/kg bw rat oral 13-week dermal absorption {"dose":"Safety evaluation (including calculation of the MoS) CALCULATION OF THE MARGIN OF SAFETY (HC Blue n° 12) (oxidative and non-oxidative) Maximum absorption through the skin A (µg/cm2) = 21.7 µg/cm² Skin Area surface SAS (cm2) = 700 cm2 Dermal absorption per treatment SAS x A x 0.001 = 15.19 mg Typical body weight of human = 60 kg Systemic exposure...","effect":"Human data No data submitted 3.3.12. Special investigations No data submitted 3.3.13. Safety evaluation (including calculation of the MoS) CALCULATION OF THE MARGIN OF SAFETY (HC Blue n° 12) (oxidative and non-oxidative) Maximum absorption through the skin A (µg/cm2) = 21.7 µg/cm² Skin Area surface SAS (cm2) = 700 cm2 Dermal absorption per treatment SAS x A x 0.001 = 15.19 mg Typical body weight of human = 60 kg Systemic exposure dose (SED) SAS x A x 0.001/60 = 0.253 mg/kg No observed adverse effect level NOAEL = 60 mg/kg bw (13-week, oral, rat) Margin of Safety NOAEL / SED = 237 3.3.14. Discussion Physico-chemical properties HC Blue n° 12 is used as a non-reactive hair colouring agent (\"Direct Dye\") in semi- permanent hair dye formulations at a maximum on-head concentration of 1.5 %, as well as a non-reactive hair colouring agent (\"Direct Dye\") in oxidative hair dye formulations at a maximum on-head concentration of 0.75 %. HC Blue n° 12 is both a secondary and a tertiary amine and thus is prone to nitrosation. It s","page":29,"pdf":"sccp_o_117.pdf","row_type":"noael_study","study_id":"sccp_o_117_noael_008"}
SCCS_vision_codex NOAEL =1668 mg/kg bw rat - 28 day repeated dose toxicity {"dose":"General toxicity In acute toxicity studies in mice and rats, based on the mortality rates LD50 figures from 1668 to 1775 mg/kg bw were calculated.","effect":"hair dye formulations at a maximum on-head concentration of 0.75 %. HC Blue n° 12 is both a secondary and a tertiary amine and thus is prone to nitrosation. It should not be used in combination with nitrosating substances. The nitrosamine content should be < 50 ppb. No data submitted for the stability of the test substance in solutions or in the marketed products. General toxicity In acute toxicity studies in mice and rats, based on the mortality rates LD50 figures from 1668 to 1775 mg/kg bw were calculated. The NOAEL of the 28 day toxicity study is 316 mg/kg bw/d. The dose of 60 mg/kg bw/d is considered the NOAEL dose of subchronic toxicity. The NOAEL of maternal and developmental toxicity is 140 mg/kg bw/d. Irritation / sensitisation Undiluted HC Blue n° 12 did not cause any signs of skin irritation in the rabbit. Under the conditions of the test, undiluted HC Blue n° 12 caused transient eye irritation in rabbits.","page":29,"pdf":"sccp_o_117.pdf","row_type":"noael_study","study_id":"sccp_o_117_noael_010"}
SCCS_vision_codex NOAEL =30 mg/kg bw rat oral 90-day irritation {"dose":"In the 90-day study with rats, 30 mg/kg bw was considered to be the NOAEL.","effect":"e, earlier called Nitroblau, was submitted in March 1992 by COLIPA1, 2. The Scientific Committee on Cosmetology (SCC) adopted at its 53rd plenary meeting on 25 June 1993 an opinion (SPC/1077/93) with the final conclusion that: “Nitroblau was found moderately toxic in the acute oral toxicity test and slightly toxic after dermal administration to rabbits. Nitroblau showed no signs of irritation. The sensitization test was carried out inadequately. In the 90-day study with rats, 30 mg/kg bw was considered to be the NOAEL. In the teratogenicity study, no irreversible structural changes were observed in the foetuses of the rat, after administration of 140 mg/kg bw. Nitroblau is not genotoxic. The cutaneous absorption was 1% of the administered 14C for the hair dyeing formulation. For normal use of hair dye, the following calculation can be made: 750 mg nitroblau comes in contact with the human skin in permanent hair dye condition (based on a usage volume of 100 ml containing 0.75% nitroblau). With a maximal penetration of 1%, this r","page":5,"pdf":"sccp_o_117.pdf","row_type":"noael_study","study_id":"sccp_o_117_noael_001"}
SCCS_vision_codex NOAEL =140 mg/kg bw rat dermal 90-day dermal absorption {"dose":"With a penetration of 1%; this results in a dermal absorption of 5.25 mg per treatment, which is 0.0875 mg/kg bw So a margin of safety of 240 can be calculated between the figure for human exposure to oxidative hair dye and the no adverse effect level found in rats in the 90-day study (limited study, only 1 dose tested).","effect":"With a penetration of 1%; this results in a dermal absorption of 5.25 mg per treatment, which is 0.0875 mg/kg bw So a margin of safety of 240 can be calculated between the figure for human exposure to oxidative hair dye and the no adverse effect level found in rats in the 90-day study (limited study, only 1 dose tested). It should be noted that no effects were observed in the teratogenicity study at 140 mg/kg bw. For the semi-permanent hair dye a safety margin of 343 can be calculated. It should be noted that the NOAEL stems from a daily exposure for 90 days, whereas human exposure to permanent hair dye is unlikely to be more frequent than once a month and human exposure to semi-permanent hair dye is unlikely to be more than once a week.” Submission II for HC Blue n° 12 was submitted in December 1993 by COLIPA². The Scientific Committee on Cosmetic products and Non-Food Products intended for Consumers (SCCNFP) adopted at its plenary meeting on 23 June 1999 an opinion (SCCNFP/0140/99) with the conclusion that: “The SCCNFP is o","page":5,"pdf":"sccp_o_117.pdf","row_type":"noael_study","study_id":"sccp_o_117_noael_002"}
SCCS_vision_codex NOAEL =316 mg/kg bw/d - - 28 day NOAEL study {"citation":"Ref.: 21","dose":"igh dose females also the coagulation time was raised.","effect":"igh dose females also the coagulation time was raised. Clinical chemistry showed changes in uric acid (lowered at high dose, both sexes) and bilirubin (raised at high dose, both sexes). Absolute and relative spleen weights were increased at the high dose but significance was reached only in males. Also in the high dose group liver weight was increased (females only). At the high dose with both sexes in the spleen lymphoid depletion and congestion as well as induction of haematopoesis were observed. Conclusion The NOAEL of the 28 day toxicity study is 316 mg/kg bw/d. Ref.: 21","page":18,"pdf":"sccp_o_117.pdf","row_type":"noael_study","study_id":"sccp_o_117_noael_003"}
SCCS_vision_codex NOAEL =60 mg/kg bw/d rat oral 13 weeks NOAEL study {"citation":"Ref.: 22, 23 Rat Study 2 Guideline: / Species/strain: Wistar rats Bor","dose":"Feed and water consumption and body weight gain were in the physiological range and no dose related changes were noted.","effect":"ctivity measurement and ophthalmoscopic examination did not show a difference between control and test groups. Feed and water consumption and body weight gain were in the physiological range and no dose related changes were noted. Also neither haematology, biochemistry or urinalysis revealed test substance related changes. The histomorphological investigation revealed no substance-related alterations. Conclusion Under the conditions of the study the highest dose tested dose of 60 mg/kg bw/d was found as being the NOAEL dose. However, only a limited number of animals (5 per sex and dose) were analysed histopathologically. Ref.: 22, 23 Rat Study 2 Guideline: / Species/strain: Wistar rats Bor.Wis.W. (SPF) Group size: 12 per sex Test substance: Nitroblau hydrochloride in distilled water Batch: L4/154 Purity: 93.2 % (HPLC) Dose: 30 mg/kg bw/d Route: oral, gavage Exposure: 13 weeks GLP: in compliance The test substance was administered at 30 mg/kg bw/d to 12 male and 12 female Wistar rats by oral gavage for 13 weeks. No control g","page":19,"pdf":"sccp_o_117.pdf","row_type":"noael_study","study_id":"sccp_o_117_noael_004"}
SCCS_vision_codex NOAEL =140 mg/kg bw/d human - developmental developmental toxicity {"citation":"Ref.: 34 Comment The highest dose of 140 mg/kg bw is too low for hazard assessment","dose":"Results With the exception of violet staining of urine (all treated animals) and fur, paw and tail (high dose group) no clinical signs were noted.","effect":"mperfections and the remainder was subjected to skeletal examination. Results With the exception of violet staining of urine (all treated animals) and fur, paw and tail (high dose group) no clinical signs were noted. Food consumption and body weight changes of the dams were not significantly different from controls. Foetal weight, sex ratio, placental weight, number of resorptions and corpora lutea were not influenced by treatment. Examination of skeleton and viscera revealed no relevant findings. Conclusion The NOAEL of maternal and developmental toxicity in this study is 140 mg/kg bw/d. Ref.: 34 Comment The highest dose of 140 mg/kg bw is too low for hazard assessment. For this, the highest dose used should be 1000 mg/kg bw and should induce toxicity. 3.3.9. Toxicokinetics 3.3.9.1. Toxicokinetics in vitro Bioavailability across intestinal barrier in TC-7 (human intestinal epithelial) cells Guideline: / Cells: Human intestinal epithelial cell line TC-7 Test substance: HC Blue n° 12 Batch: 29/30 Purity: 93.9 area% (HPLC) T","page":27,"pdf":"sccp_o_117.pdf","row_type":"noael_study","study_id":"sccp_o_117_noael_006"}
SCCS_vision_codex NOAEL =0.253 mg/kg rat oral 13-week dermal absorption {"dose":"Safety evaluation (including calculation of the MoS) CALCULATION OF THE MARGIN OF SAFETY (HC Blue n° 12) (oxidative and non-oxidative) Maximum absorption through the skin A (µg/cm2) = 21.7 µg/cm² Skin Area surface SAS (cm2) = 700 cm2 Dermal absorption per treatment SAS x A x 0.001 = 15.19 mg Typical body weight of human = 60 kg Systemic exposure...","effect":"icity No data submitted 3.3.11. Human data No data submitted 3.3.12. Special investigations No data submitted 3.3.13. Safety evaluation (including calculation of the MoS) CALCULATION OF THE MARGIN OF SAFETY (HC Blue n° 12) (oxidative and non-oxidative) Maximum absorption through the skin A (µg/cm2) = 21.7 µg/cm² Skin Area surface SAS (cm2) = 700 cm2 Dermal absorption per treatment SAS x A x 0.001 = 15.19 mg Typical body weight of human = 60 kg Systemic exposure dose (SED) SAS x A x 0.001/60 = 0.253 mg/kg No observed adverse effect level NOAEL = 60 mg/kg bw (13-week, oral, rat) Margin of Safety NOAEL / SED = 237 3.3.14. Discussion Physico-chemical properties HC Blue n° 12 is used as a non-reactive hair colouring agent (\"Direct Dye\") in semi- permanent hair dye formulations at a maximum on-head concentration of 1.5 %, as well as a non-reactive hair colouring agent (\"Direct Dye\") in oxidative hair dye formulations at a maximum on-head concentration of 0.75 %. HC Blue n° 12 is both a secondary and a tertiary amine and thus is prone to nitrosation","page":29,"pdf":"sccp_o_117.pdf","row_type":"noael_study","study_id":"sccp_o_117_noael_007"}
SCCS_vision_codex NOAEL =60 mg/kg bw rat oral 13-week dermal absorption {"dose":"Safety evaluation (including calculation of the MoS) CALCULATION OF THE MARGIN OF SAFETY (HC Blue n° 12) (oxidative and non-oxidative) Maximum absorption through the skin A (µg/cm2) = 21.7 µg/cm² Skin Area surface SAS (cm2) = 700 cm2 Dermal absorption per treatment SAS x A x 0.001 = 15.19 mg Typical body weight of human = 60 kg Systemic exposure...","effect":"Human data No data submitted 3.3.12. Special investigations No data submitted 3.3.13. Safety evaluation (including calculation of the MoS) CALCULATION OF THE MARGIN OF SAFETY (HC Blue n° 12) (oxidative and non-oxidative) Maximum absorption through the skin A (µg/cm2) = 21.7 µg/cm² Skin Area surface SAS (cm2) = 700 cm2 Dermal absorption per treatment SAS x A x 0.001 = 15.19 mg Typical body weight of human = 60 kg Systemic exposure dose (SED) SAS x A x 0.001/60 = 0.253 mg/kg No observed adverse effect level NOAEL = 60 mg/kg bw (13-week, oral, rat) Margin of Safety NOAEL / SED = 237 3.3.14. Discussion Physico-chemical properties HC Blue n° 12 is used as a non-reactive hair colouring agent (\"Direct Dye\") in semi- permanent hair dye formulations at a maximum on-head concentration of 1.5 %, as well as a non-reactive hair colouring agent (\"Direct Dye\") in oxidative hair dye formulations at a maximum on-head concentration of 0.75 %. HC Blue n° 12 is both a secondary and a tertiary amine and thus is prone to nitrosation. It s","page":29,"pdf":"sccp_o_117.pdf","row_type":"noael_study","study_id":"sccp_o_117_noael_008"}
SCCS_vision_codex NOAEL =1668 mg/kg bw rat - 28 day repeated dose toxicity {"dose":"General toxicity In acute toxicity studies in mice and rats, based on the mortality rates LD50 figures from 1668 to 1775 mg/kg bw were calculated.","effect":"hair dye formulations at a maximum on-head concentration of 0.75 %. HC Blue n° 12 is both a secondary and a tertiary amine and thus is prone to nitrosation. It should not be used in combination with nitrosating substances. The nitrosamine content should be < 50 ppb. No data submitted for the stability of the test substance in solutions or in the marketed products. General toxicity In acute toxicity studies in mice and rats, based on the mortality rates LD50 figures from 1668 to 1775 mg/kg bw were calculated. The NOAEL of the 28 day toxicity study is 316 mg/kg bw/d. The dose of 60 mg/kg bw/d is considered the NOAEL dose of subchronic toxicity. The NOAEL of maternal and developmental toxicity is 140 mg/kg bw/d. Irritation / sensitisation Undiluted HC Blue n° 12 did not cause any signs of skin irritation in the rabbit. Under the conditions of the test, undiluted HC Blue n° 12 caused transient eye irritation in rabbits.","page":29,"pdf":"sccp_o_117.pdf","row_type":"noael_study","study_id":"sccp_o_117_noael_010"}
SCCS_vision_codex NOAEL =30 mg/kg bw rat oral 90-day irritation {"dose":"In the 90-day study with rats, 30 mg/kg bw was considered to be the NOAEL.","effect":"e, earlier called Nitroblau, was submitted in March 1992 by COLIPA1, 2. The Scientific Committee on Cosmetology (SCC) adopted at its 53rd plenary meeting on 25 June 1993 an opinion (SPC/1077/93) with the final conclusion that: “Nitroblau was found moderately toxic in the acute oral toxicity test and slightly toxic after dermal administration to rabbits. Nitroblau showed no signs of irritation. The sensitization test was carried out inadequately. In the 90-day study with rats, 30 mg/kg bw was considered to be the NOAEL. In the teratogenicity study, no irreversible structural changes were observed in the foetuses of the rat, after administration of 140 mg/kg bw. Nitroblau is not genotoxic. The cutaneous absorption was 1% of the administered 14C for the hair dyeing formulation. For normal use of hair dye, the following calculation can be made: 750 mg nitroblau comes in contact with the human skin in permanent hair dye condition (based on a usage volume of 100 ml containing 0.75% nitroblau). With a maximal penetration of 1%, this r","page":5,"pdf":"sccp_o_117.pdf","row_type":"noael_study","study_id":"sccp_o_117_noael_001"}
SCCS_vision_codex NOAEL =140 mg/kg bw rat dermal 90-day dermal absorption {"dose":"With a penetration of 1%; this results in a dermal absorption of 5.25 mg per treatment, which is 0.0875 mg/kg bw So a margin of safety of 240 can be calculated between the figure for human exposure to oxidative hair dye and the no adverse effect level found in rats in the 90-day study (limited study, only 1 dose tested).","effect":"With a penetration of 1%; this results in a dermal absorption of 5.25 mg per treatment, which is 0.0875 mg/kg bw So a margin of safety of 240 can be calculated between the figure for human exposure to oxidative hair dye and the no adverse effect level found in rats in the 90-day study (limited study, only 1 dose tested). It should be noted that no effects were observed in the teratogenicity study at 140 mg/kg bw. For the semi-permanent hair dye a safety margin of 343 can be calculated. It should be noted that the NOAEL stems from a daily exposure for 90 days, whereas human exposure to permanent hair dye is unlikely to be more frequent than once a month and human exposure to semi-permanent hair dye is unlikely to be more than once a week.” Submission II for HC Blue n° 12 was submitted in December 1993 by COLIPA². The Scientific Committee on Cosmetic products and Non-Food Products intended for Consumers (SCCNFP) adopted at its plenary meeting on 23 June 1999 an opinion (SCCNFP/0140/99) with the conclusion that: “The SCCNFP is o","page":5,"pdf":"sccp_o_117.pdf","row_type":"noael_study","study_id":"sccp_o_117_noael_002"}
SCCS_vision_codex NOAEL =316 mg/kg bw/d - - 28 day NOAEL study {"citation":"Ref.: 21","dose":"igh dose females also the coagulation time was raised.","effect":"igh dose females also the coagulation time was raised. Clinical chemistry showed changes in uric acid (lowered at high dose, both sexes) and bilirubin (raised at high dose, both sexes). Absolute and relative spleen weights were increased at the high dose but significance was reached only in males. Also in the high dose group liver weight was increased (females only). At the high dose with both sexes in the spleen lymphoid depletion and congestion as well as induction of haematopoesis were observed. Conclusion The NOAEL of the 28 day toxicity study is 316 mg/kg bw/d. Ref.: 21","page":18,"pdf":"sccp_o_117.pdf","row_type":"noael_study","study_id":"sccp_o_117_noael_003"}
SCCS_vision_codex NOAEL =60 mg/kg bw/d rat oral 13 weeks NOAEL study {"citation":"Ref.: 22, 23 Rat Study 2 Guideline: / Species/strain: Wistar rats Bor","dose":"Feed and water consumption and body weight gain were in the physiological range and no dose related changes were noted.","effect":"ctivity measurement and ophthalmoscopic examination did not show a difference between control and test groups. Feed and water consumption and body weight gain were in the physiological range and no dose related changes were noted. Also neither haematology, biochemistry or urinalysis revealed test substance related changes. The histomorphological investigation revealed no substance-related alterations. Conclusion Under the conditions of the study the highest dose tested dose of 60 mg/kg bw/d was found as being the NOAEL dose. However, only a limited number of animals (5 per sex and dose) were analysed histopathologically. Ref.: 22, 23 Rat Study 2 Guideline: / Species/strain: Wistar rats Bor.Wis.W. (SPF) Group size: 12 per sex Test substance: Nitroblau hydrochloride in distilled water Batch: L4/154 Purity: 93.2 % (HPLC) Dose: 30 mg/kg bw/d Route: oral, gavage Exposure: 13 weeks GLP: in compliance The test substance was administered at 30 mg/kg bw/d to 12 male and 12 female Wistar rats by oral gavage for 13 weeks. No control g","page":19,"pdf":"sccp_o_117.pdf","row_type":"noael_study","study_id":"sccp_o_117_noael_004"}
SCCS_vision_codex NOAEL =140 mg/kg bw/d human - developmental developmental toxicity {"citation":"Ref.: 34 Comment The highest dose of 140 mg/kg bw is too low for hazard assessment","dose":"Results With the exception of violet staining of urine (all treated animals) and fur, paw and tail (high dose group) no clinical signs were noted.","effect":"mperfections and the remainder was subjected to skeletal examination. Results With the exception of violet staining of urine (all treated animals) and fur, paw and tail (high dose group) no clinical signs were noted. Food consumption and body weight changes of the dams were not significantly different from controls. Foetal weight, sex ratio, placental weight, number of resorptions and corpora lutea were not influenced by treatment. Examination of skeleton and viscera revealed no relevant findings. Conclusion The NOAEL of maternal and developmental toxicity in this study is 140 mg/kg bw/d. Ref.: 34 Comment The highest dose of 140 mg/kg bw is too low for hazard assessment. For this, the highest dose used should be 1000 mg/kg bw and should induce toxicity. 3.3.9. Toxicokinetics 3.3.9.1. Toxicokinetics in vitro Bioavailability across intestinal barrier in TC-7 (human intestinal epithelial) cells Guideline: / Cells: Human intestinal epithelial cell line TC-7 Test substance: HC Blue n° 12 Batch: 29/30 Purity: 93.9 area% (HPLC) T","page":27,"pdf":"sccp_o_117.pdf","row_type":"noael_study","study_id":"sccp_o_117_noael_006"}
SCCS_vision_codex NOAEL =0.253 mg/kg rat oral 13-week dermal absorption {"dose":"Safety evaluation (including calculation of the MoS) CALCULATION OF THE MARGIN OF SAFETY (HC Blue n° 12) (oxidative and non-oxidative) Maximum absorption through the skin A (µg/cm2) = 21.7 µg/cm² Skin Area surface SAS (cm2) = 700 cm2 Dermal absorption per treatment SAS x A x 0.001 = 15.19 mg Typical body weight of human = 60 kg Systemic exposure...","effect":"icity No data submitted 3.3.11. Human data No data submitted 3.3.12. Special investigations No data submitted 3.3.13. Safety evaluation (including calculation of the MoS) CALCULATION OF THE MARGIN OF SAFETY (HC Blue n° 12) (oxidative and non-oxidative) Maximum absorption through the skin A (µg/cm2) = 21.7 µg/cm² Skin Area surface SAS (cm2) = 700 cm2 Dermal absorption per treatment SAS x A x 0.001 = 15.19 mg Typical body weight of human = 60 kg Systemic exposure dose (SED) SAS x A x 0.001/60 = 0.253 mg/kg No observed adverse effect level NOAEL = 60 mg/kg bw (13-week, oral, rat) Margin of Safety NOAEL / SED = 237 3.3.14. Discussion Physico-chemical properties HC Blue n° 12 is used as a non-reactive hair colouring agent (\"Direct Dye\") in semi- permanent hair dye formulations at a maximum on-head concentration of 1.5 %, as well as a non-reactive hair colouring agent (\"Direct Dye\") in oxidative hair dye formulations at a maximum on-head concentration of 0.75 %. HC Blue n° 12 is both a secondary and a tertiary amine and thus is prone to nitrosation","page":29,"pdf":"sccp_o_117.pdf","row_type":"noael_study","study_id":"sccp_o_117_noael_007"}
SCCS_vision_codex NOAEL =60 mg/kg bw rat oral 13-week dermal absorption {"dose":"Safety evaluation (including calculation of the MoS) CALCULATION OF THE MARGIN OF SAFETY (HC Blue n° 12) (oxidative and non-oxidative) Maximum absorption through the skin A (µg/cm2) = 21.7 µg/cm² Skin Area surface SAS (cm2) = 700 cm2 Dermal absorption per treatment SAS x A x 0.001 = 15.19 mg Typical body weight of human = 60 kg Systemic exposure...","effect":"Human data No data submitted 3.3.12. Special investigations No data submitted 3.3.13. Safety evaluation (including calculation of the MoS) CALCULATION OF THE MARGIN OF SAFETY (HC Blue n° 12) (oxidative and non-oxidative) Maximum absorption through the skin A (µg/cm2) = 21.7 µg/cm² Skin Area surface SAS (cm2) = 700 cm2 Dermal absorption per treatment SAS x A x 0.001 = 15.19 mg Typical body weight of human = 60 kg Systemic exposure dose (SED) SAS x A x 0.001/60 = 0.253 mg/kg No observed adverse effect level NOAEL = 60 mg/kg bw (13-week, oral, rat) Margin of Safety NOAEL / SED = 237 3.3.14. Discussion Physico-chemical properties HC Blue n° 12 is used as a non-reactive hair colouring agent (\"Direct Dye\") in semi- permanent hair dye formulations at a maximum on-head concentration of 1.5 %, as well as a non-reactive hair colouring agent (\"Direct Dye\") in oxidative hair dye formulations at a maximum on-head concentration of 0.75 %. HC Blue n° 12 is both a secondary and a tertiary amine and thus is prone to nitrosation. It s","page":29,"pdf":"sccp_o_117.pdf","row_type":"noael_study","study_id":"sccp_o_117_noael_008"}
SCCS_vision_codex NOAEL =1668 mg/kg bw rat - 28 day repeated dose toxicity {"dose":"General toxicity In acute toxicity studies in mice and rats, based on the mortality rates LD50 figures from 1668 to 1775 mg/kg bw were calculated.","effect":"hair dye formulations at a maximum on-head concentration of 0.75 %. HC Blue n° 12 is both a secondary and a tertiary amine and thus is prone to nitrosation. It should not be used in combination with nitrosating substances. The nitrosamine content should be < 50 ppb. No data submitted for the stability of the test substance in solutions or in the marketed products. General toxicity In acute toxicity studies in mice and rats, based on the mortality rates LD50 figures from 1668 to 1775 mg/kg bw were calculated. The NOAEL of the 28 day toxicity study is 316 mg/kg bw/d. The dose of 60 mg/kg bw/d is considered the NOAEL dose of subchronic toxicity. The NOAEL of maternal and developmental toxicity is 140 mg/kg bw/d. Irritation / sensitisation Undiluted HC Blue n° 12 did not cause any signs of skin irritation in the rabbit. Under the conditions of the test, undiluted HC Blue n° 12 caused transient eye irritation in rabbits.","page":29,"pdf":"sccp_o_117.pdf","row_type":"noael_study","study_id":"sccp_o_117_noael_010"}
SCCS_vision_codex NOAEL =30 mg/kg bw rat oral 90-day irritation {"dose":"In the 90-day study with rats, 30 mg/kg bw was considered to be the NOAEL.","effect":"e, earlier called Nitroblau, was submitted in March 1992 by COLIPA1, 2. The Scientific Committee on Cosmetology (SCC) adopted at its 53rd plenary meeting on 25 June 1993 an opinion (SPC/1077/93) with the final conclusion that: “Nitroblau was found moderately toxic in the acute oral toxicity test and slightly toxic after dermal administration to rabbits. Nitroblau showed no signs of irritation. The sensitization test was carried out inadequately. In the 90-day study with rats, 30 mg/kg bw was considered to be the NOAEL. In the teratogenicity study, no irreversible structural changes were observed in the foetuses of the rat, after administration of 140 mg/kg bw. Nitroblau is not genotoxic. The cutaneous absorption was 1% of the administered 14C for the hair dyeing formulation. For normal use of hair dye, the following calculation can be made: 750 mg nitroblau comes in contact with the human skin in permanent hair dye condition (based on a usage volume of 100 ml containing 0.75% nitroblau). With a maximal penetration of 1%, this r","page":5,"pdf":"sccp_o_117.pdf","row_type":"noael_study","study_id":"sccp_o_117_noael_001"}
SCCS_vision_codex NOAEL =140 mg/kg bw rat dermal 90-day dermal absorption {"dose":"With a penetration of 1%; this results in a dermal absorption of 5.25 mg per treatment, which is 0.0875 mg/kg bw So a margin of safety of 240 can be calculated between the figure for human exposure to oxidative hair dye and the no adverse effect level found in rats in the 90-day study (limited study, only 1 dose tested).","effect":"With a penetration of 1%; this results in a dermal absorption of 5.25 mg per treatment, which is 0.0875 mg/kg bw So a margin of safety of 240 can be calculated between the figure for human exposure to oxidative hair dye and the no adverse effect level found in rats in the 90-day study (limited study, only 1 dose tested). It should be noted that no effects were observed in the teratogenicity study at 140 mg/kg bw. For the semi-permanent hair dye a safety margin of 343 can be calculated. It should be noted that the NOAEL stems from a daily exposure for 90 days, whereas human exposure to permanent hair dye is unlikely to be more frequent than once a month and human exposure to semi-permanent hair dye is unlikely to be more than once a week.” Submission II for HC Blue n° 12 was submitted in December 1993 by COLIPA². The Scientific Committee on Cosmetic products and Non-Food Products intended for Consumers (SCCNFP) adopted at its plenary meeting on 23 June 1999 an opinion (SCCNFP/0140/99) with the conclusion that: “The SCCNFP is o","page":5,"pdf":"sccp_o_117.pdf","row_type":"noael_study","study_id":"sccp_o_117_noael_002"}
SCCS_vision_codex NOAEL =316 mg/kg bw/d - - 28 day NOAEL study {"citation":"Ref.: 21","dose":"igh dose females also the coagulation time was raised.","effect":"igh dose females also the coagulation time was raised. Clinical chemistry showed changes in uric acid (lowered at high dose, both sexes) and bilirubin (raised at high dose, both sexes). Absolute and relative spleen weights were increased at the high dose but significance was reached only in males. Also in the high dose group liver weight was increased (females only). At the high dose with both sexes in the spleen lymphoid depletion and congestion as well as induction of haematopoesis were observed. Conclusion The NOAEL of the 28 day toxicity study is 316 mg/kg bw/d. Ref.: 21","page":18,"pdf":"sccp_o_117.pdf","row_type":"noael_study","study_id":"sccp_o_117_noael_003"}
SCCS_vision_codex NOAEL =60 mg/kg bw/d rat oral 13 weeks NOAEL study {"citation":"Ref.: 22, 23 Rat Study 2 Guideline: / Species/strain: Wistar rats Bor","dose":"Feed and water consumption and body weight gain were in the physiological range and no dose related changes were noted.","effect":"ctivity measurement and ophthalmoscopic examination did not show a difference between control and test groups. Feed and water consumption and body weight gain were in the physiological range and no dose related changes were noted. Also neither haematology, biochemistry or urinalysis revealed test substance related changes. The histomorphological investigation revealed no substance-related alterations. Conclusion Under the conditions of the study the highest dose tested dose of 60 mg/kg bw/d was found as being the NOAEL dose. However, only a limited number of animals (5 per sex and dose) were analysed histopathologically. Ref.: 22, 23 Rat Study 2 Guideline: / Species/strain: Wistar rats Bor.Wis.W. (SPF) Group size: 12 per sex Test substance: Nitroblau hydrochloride in distilled water Batch: L4/154 Purity: 93.2 % (HPLC) Dose: 30 mg/kg bw/d Route: oral, gavage Exposure: 13 weeks GLP: in compliance The test substance was administered at 30 mg/kg bw/d to 12 male and 12 female Wistar rats by oral gavage for 13 weeks. No control g","page":19,"pdf":"sccp_o_117.pdf","row_type":"noael_study","study_id":"sccp_o_117_noael_004"}
SCCS_vision_codex NOAEL =140 mg/kg bw/d human - developmental developmental toxicity {"citation":"Ref.: 34 Comment The highest dose of 140 mg/kg bw is too low for hazard assessment","dose":"Results With the exception of violet staining of urine (all treated animals) and fur, paw and tail (high dose group) no clinical signs were noted.","effect":"mperfections and the remainder was subjected to skeletal examination. Results With the exception of violet staining of urine (all treated animals) and fur, paw and tail (high dose group) no clinical signs were noted. Food consumption and body weight changes of the dams were not significantly different from controls. Foetal weight, sex ratio, placental weight, number of resorptions and corpora lutea were not influenced by treatment. Examination of skeleton and viscera revealed no relevant findings. Conclusion The NOAEL of maternal and developmental toxicity in this study is 140 mg/kg bw/d. Ref.: 34 Comment The highest dose of 140 mg/kg bw is too low for hazard assessment. For this, the highest dose used should be 1000 mg/kg bw and should induce toxicity. 3.3.9. Toxicokinetics 3.3.9.1. Toxicokinetics in vitro Bioavailability across intestinal barrier in TC-7 (human intestinal epithelial) cells Guideline: / Cells: Human intestinal epithelial cell line TC-7 Test substance: HC Blue n° 12 Batch: 29/30 Purity: 93.9 area% (HPLC) T","page":27,"pdf":"sccp_o_117.pdf","row_type":"noael_study","study_id":"sccp_o_117_noael_006"}
SCCS_vision_codex NOAEL =0.253 mg/kg rat oral 13-week dermal absorption {"dose":"Safety evaluation (including calculation of the MoS) CALCULATION OF THE MARGIN OF SAFETY (HC Blue n° 12) (oxidative and non-oxidative) Maximum absorption through the skin A (µg/cm2) = 21.7 µg/cm² Skin Area surface SAS (cm2) = 700 cm2 Dermal absorption per treatment SAS x A x 0.001 = 15.19 mg Typical body weight of human = 60 kg Systemic exposure...","effect":"icity No data submitted 3.3.11. Human data No data submitted 3.3.12. Special investigations No data submitted 3.3.13. Safety evaluation (including calculation of the MoS) CALCULATION OF THE MARGIN OF SAFETY (HC Blue n° 12) (oxidative and non-oxidative) Maximum absorption through the skin A (µg/cm2) = 21.7 µg/cm² Skin Area surface SAS (cm2) = 700 cm2 Dermal absorption per treatment SAS x A x 0.001 = 15.19 mg Typical body weight of human = 60 kg Systemic exposure dose (SED) SAS x A x 0.001/60 = 0.253 mg/kg No observed adverse effect level NOAEL = 60 mg/kg bw (13-week, oral, rat) Margin of Safety NOAEL / SED = 237 3.3.14. Discussion Physico-chemical properties HC Blue n° 12 is used as a non-reactive hair colouring agent (\"Direct Dye\") in semi- permanent hair dye formulations at a maximum on-head concentration of 1.5 %, as well as a non-reactive hair colouring agent (\"Direct Dye\") in oxidative hair dye formulations at a maximum on-head concentration of 0.75 %. HC Blue n° 12 is both a secondary and a tertiary amine and thus is prone to nitrosation","page":29,"pdf":"sccp_o_117.pdf","row_type":"noael_study","study_id":"sccp_o_117_noael_007"}
SCCS_vision_codex NOAEL =60 mg/kg bw rat oral 13-week dermal absorption {"dose":"Safety evaluation (including calculation of the MoS) CALCULATION OF THE MARGIN OF SAFETY (HC Blue n° 12) (oxidative and non-oxidative) Maximum absorption through the skin A (µg/cm2) = 21.7 µg/cm² Skin Area surface SAS (cm2) = 700 cm2 Dermal absorption per treatment SAS x A x 0.001 = 15.19 mg Typical body weight of human = 60 kg Systemic exposure...","effect":"Human data No data submitted 3.3.12. Special investigations No data submitted 3.3.13. Safety evaluation (including calculation of the MoS) CALCULATION OF THE MARGIN OF SAFETY (HC Blue n° 12) (oxidative and non-oxidative) Maximum absorption through the skin A (µg/cm2) = 21.7 µg/cm² Skin Area surface SAS (cm2) = 700 cm2 Dermal absorption per treatment SAS x A x 0.001 = 15.19 mg Typical body weight of human = 60 kg Systemic exposure dose (SED) SAS x A x 0.001/60 = 0.253 mg/kg No observed adverse effect level NOAEL = 60 mg/kg bw (13-week, oral, rat) Margin of Safety NOAEL / SED = 237 3.3.14. Discussion Physico-chemical properties HC Blue n° 12 is used as a non-reactive hair colouring agent (\"Direct Dye\") in semi- permanent hair dye formulations at a maximum on-head concentration of 1.5 %, as well as a non-reactive hair colouring agent (\"Direct Dye\") in oxidative hair dye formulations at a maximum on-head concentration of 0.75 %. HC Blue n° 12 is both a secondary and a tertiary amine and thus is prone to nitrosation. It s","page":29,"pdf":"sccp_o_117.pdf","row_type":"noael_study","study_id":"sccp_o_117_noael_008"}
SCCS_vision_codex NOAEL =1668 mg/kg bw rat - 28 day repeated dose toxicity {"dose":"General toxicity In acute toxicity studies in mice and rats, based on the mortality rates LD50 figures from 1668 to 1775 mg/kg bw were calculated.","effect":"hair dye formulations at a maximum on-head concentration of 0.75 %. HC Blue n° 12 is both a secondary and a tertiary amine and thus is prone to nitrosation. It should not be used in combination with nitrosating substances. The nitrosamine content should be < 50 ppb. No data submitted for the stability of the test substance in solutions or in the marketed products. General toxicity In acute toxicity studies in mice and rats, based on the mortality rates LD50 figures from 1668 to 1775 mg/kg bw were calculated. The NOAEL of the 28 day toxicity study is 316 mg/kg bw/d. The dose of 60 mg/kg bw/d is considered the NOAEL dose of subchronic toxicity. The NOAEL of maternal and developmental toxicity is 140 mg/kg bw/d. Irritation / sensitisation Undiluted HC Blue n° 12 did not cause any signs of skin irritation in the rabbit. Under the conditions of the test, undiluted HC Blue n° 12 caused transient eye irritation in rabbits.","page":29,"pdf":"sccp_o_117.pdf","row_type":"noael_study","study_id":"sccp_o_117_noael_010"}
UnifiedCodex:SCCS_SHADOW:beta.noael_studies 24 endpoints
Source Endpoint Type Value Unit Species Route Duration Study Type Reference
UnifiedCodex:SCCS_SHADOW:beta.noael_studies - 316 mg/kg bw/d - - 28 day - SOURCE_SUBDIR=sccp_o_117; REPORT_TITLE=OPINION ON HC Blue n° 12 COLIPA n° B73; OPINION_NUMBER=SCCP/1135/07; COMMITTEE=Scientific Committee on Consumer Products (SCCP); REPORT_DATE=18 December 2007; VALUE_TEXT=316; DOSE=igh dose females also the coagulation time was raised.; EFFECT=igh dose females also the coagulation time was raised. Clinical chemistry showed changes in uric acid (lowered at high dose, both sexes) and bilirubin (raised at high dose, both sexes). Absolute and relative spleen weights were increased at the high dose but significance was reached only in males. Also in the high dose group liver weight was increased (females only). At the high dose with both sexes in the spleen lymphoid depletion and congestion as well as induction of haematopoesis were observed. Conclusion The NOAEL of the 28 day toxicity study is 316 mg/kg bw/d. Ref.: 21; CITATION=Ref.: 21; CITATION_NUMBERS=[21]; REFERENCE=Ref.: 21; DETAILS_JSON={"cas_number":"104576-93-0","citation":"Ref.: 21","dose":"igh dose females also the coagulation time was raised.","duration":"28 day","effect":"igh dose females also the coagulation time was raised. Clinical chemistry showed changes in uric acid (lowered at high dose, both sexes) and bilirubin (raised at high dose, both sexes). Absolute and relative spleen weights were increased at the high dose but significance was reached only in males. Also in the high dose group liver weight was increased (females only). At the high dose with both sexes in the spleen lymphoid depletion and congestion as well as induction of haematopoesis were observed. Conclusion The NOAEL of the 28 day toxicity study is 316 mg/kg bw/d. Ref.: 21","endpoint":"","ingredient":"HC Blue No. 12","loael_value":"","noael_unit":"mg/kg bw/d","noael_value":"316","page":18,"route":"","species":"","study_id":"sccp_o_117_noael_003"}
UnifiedCodex:SCCS_SHADOW:beta.noael_studies - 60 mg/kg bw/d rat oral 13 weeks - SOURCE_SUBDIR=sccp_o_117; REPORT_TITLE=OPINION ON HC Blue n° 12 COLIPA n° B73; OPINION_NUMBER=SCCP/1135/07; COMMITTEE=Scientific Committee on Consumer Products (SCCP); REPORT_DATE=18 December 2007; VALUE_TEXT=60; DOSE=Feed and water consumption and body weight gain were in the physiological range and no dose related changes were noted.; EFFECT=ctivity measurement and ophthalmoscopic examination did not show a difference between control and test groups. Feed and water consumption and body weight gain were in the physiological range and no dose related changes were noted. Also neither haematology, biochemistry or urinalysis revealed test substance related changes. The histomorphological investigation revealed no substance-related alterations. Conclusion Under the conditions of the study the highest dose tested dose of 60 mg/kg bw/d was found as being the NOAEL dose. However, only a limited number of animals (5 per sex and dose) were analysed histopathologically. Ref.: 22, 23 Rat Study 2 Guideline: / Species/strain: Wistar rats Bor.Wis.W. (SPF) Group size: 12 per sex Test substance: Nitroblau hydrochloride in distilled water Batch: L4/154 Purity: 93.2 % (HPLC) Dose: 30 mg/kg bw/d Route: oral, gavage Exposure: 13 weeks GLP: in compliance The test substance was administered at 30 mg/kg bw/d to 12 male and 12 female Wistar rats by oral gavage for 13 weeks. No control g; CITATION=Ref.: 22, 23 Rat Study 2 Guideline: / Species/strain: Wistar rats Bor; CITATION_NUMBERS=[22,23,2]; REFERENCE=Ref.: 22, 23 Rat Study 2 Guideline: / Species/strain: Wistar rats Bor; DETAILS_JSON={"cas_number":"104576-93-0","citation":"Ref.: 22, 23 Rat Study 2 Guideline: / Species/strain: Wistar rats Bor","dose":"Feed and water consumption and body weight gain were in the physiological range and no dose related changes were noted.","duration":"13 weeks","effect":"ctivity measurement and ophthalmoscopic examination did not show a difference between control and test groups. Feed and water consumption and body weight gain were in the physiological range and no dose related changes were noted. Also neither haematology, biochemistry or urinalysis revealed test substance related changes. The histomorphological investigation revealed no substance-related alterations. Conclusion Under the conditions of the study the highest dose tested dose of 60 mg/kg bw/d was found as being the NOAEL dose. However, only a limited number of animals (5 per sex and dose) were analysed histopathologically. Ref.: 22, 23 Rat Study 2 Guideline: / Species/strain: Wistar rats Bor.Wis.W. (SPF) Group size: 12 per sex Test substance: Nitroblau hydrochloride in distilled water Batch: L4/154 Purity: 93.2 % (HPLC) Dose: 30 mg/kg bw/d Route: oral, gavage Exposure: 13 weeks GLP: in compliance The test substance was administered at 30 mg/kg bw/d to 12 male and 12 female Wistar rats by oral gavage for 13 weeks. No control g","endpoint":"","ingredient":"HC Blue No. 12","loael_value":"","noael_unit":"mg/kg bw/d","noael_value":"60","page":19,"route":"oral","species":"rat","study_id":"sccp_o_117_noael_004"}
UnifiedCodex:SCCS_SHADOW:beta.noael_studies - 316 mg/kg bw/d - - 28 day - SOURCE_SUBDIR=sccp_o_149; REPORT_TITLE=OPINION ON HC Blue n° 12 COLIPA n° B73; OPINION_NUMBER=SCCP/1209/08; COMMITTEE=Scientific Committee on Consumer Products (SCCP); REPORT_DATE=adopted on 18 December 2007; VALUE_TEXT=316; DOSE=igh dose females also the coagulation time was raised.; EFFECT=igh dose females also the coagulation time was raised. Clinical chemistry showed changes in uric acid (lowered at high dose, both sexes) and bilirubin (raised at high dose, both sexes). Absolute and relative spleen weights were increased at the high dose but significance was reached only in males. Also in the high dose group liver weight was increased (females only). At the high dose with both sexes in the spleen lymphoid depletion and congestion as well as induction of haematopoesis were observed. Conclusion The NOAEL of the 28 day toxicity study is 316 mg/kg bw/d. Ref.: 21; CITATION=Ref.: 21; CITATION_NUMBERS=[21]; REFERENCE=Ref.: 21; DETAILS_JSON={"cas_number":"104576-93-0","citation":"Ref.: 21","dose":"igh dose females also the coagulation time was raised.","duration":"28 day","effect":"igh dose females also the coagulation time was raised. Clinical chemistry showed changes in uric acid (lowered at high dose, both sexes) and bilirubin (raised at high dose, both sexes). Absolute and relative spleen weights were increased at the high dose but significance was reached only in males. Also in the high dose group liver weight was increased (females only). At the high dose with both sexes in the spleen lymphoid depletion and congestion as well as induction of haematopoesis were observed. Conclusion The NOAEL of the 28 day toxicity study is 316 mg/kg bw/d. Ref.: 21","endpoint":"","ingredient":"HC Blue No. 12","loael_value":"","noael_unit":"mg/kg bw/d","noael_value":"316","page":18,"route":"","species":"","study_id":"sccp_o_149_noael_003"}
UnifiedCodex:SCCS_SHADOW:beta.noael_studies - 60 mg/kg bw/d rat oral 13 weeks - SOURCE_SUBDIR=sccp_o_149; REPORT_TITLE=OPINION ON HC Blue n° 12 COLIPA n° B73; OPINION_NUMBER=SCCP/1209/08; COMMITTEE=Scientific Committee on Consumer Products (SCCP); REPORT_DATE=adopted on 18 December 2007; VALUE_TEXT=60; DOSE=Feed and water consumption and body weight gain were in the physiological range and no dose related changes were noted.; EFFECT=ctivity measurement and ophthalmoscopic examination did not show a difference between control and test groups. Feed and water consumption and body weight gain were in the physiological range and no dose related changes were noted. Also neither haematology, biochemistry or urinalysis revealed test substance related changes. The histomorphological investigation revealed no substance-related alterations. Conclusion Under the conditions of the study the highest dose tested dose of 60 mg/kg bw/d was found as being the NOAEL dose. However, only a limited number of animals (5 per sex and dose) were analysed histopathologically. Ref.: 22, 23 Rat Study 2 Guideline: / Species/strain: Wistar rats Bor.Wis.W. (SPF) Group size: 12 per sex Test substance: Nitroblau hydrochloride in distilled water Batch: L4/154 Purity: 93.2 % (HPLC) Dose: 30 mg/kg bw/d Route: oral, gavage Exposure: 13 weeks GLP: in compliance The test substance was administered at 30 mg/kg bw/d to 12 male and 12 female Wistar rats by oral gavage for 13 weeks. No control gr; CITATION=Ref.: 22, 23 Rat Study 2 Guideline: / Species/strain: Wistar rats Bor; CITATION_NUMBERS=[22,23,2]; REFERENCE=Ref.: 22, 23 Rat Study 2 Guideline: / Species/strain: Wistar rats Bor; DETAILS_JSON={"cas_number":"104576-93-0","citation":"Ref.: 22, 23 Rat Study 2 Guideline: / Species/strain: Wistar rats Bor","dose":"Feed and water consumption and body weight gain were in the physiological range and no dose related changes were noted.","duration":"13 weeks","effect":"ctivity measurement and ophthalmoscopic examination did not show a difference between control and test groups. Feed and water consumption and body weight gain were in the physiological range and no dose related changes were noted. Also neither haematology, biochemistry or urinalysis revealed test substance related changes. The histomorphological investigation revealed no substance-related alterations. Conclusion Under the conditions of the study the highest dose tested dose of 60 mg/kg bw/d was found as being the NOAEL dose. However, only a limited number of animals (5 per sex and dose) were analysed histopathologically. Ref.: 22, 23 Rat Study 2 Guideline: / Species/strain: Wistar rats Bor.Wis.W. (SPF) Group size: 12 per sex Test substance: Nitroblau hydrochloride in distilled water Batch: L4/154 Purity: 93.2 % (HPLC) Dose: 30 mg/kg bw/d Route: oral, gavage Exposure: 13 weeks GLP: in compliance The test substance was administered at 30 mg/kg bw/d to 12 male and 12 female Wistar rats by oral gavage for 13 weeks. No control gr","endpoint":"","ingredient":"HC Blue No. 12","loael_value":"","noael_unit":"mg/kg bw/d","noael_value":"60","page":19,"route":"oral","species":"rat","study_id":"sccp_o_149_noael_004"}
UnifiedCodex:SCCS_SHADOW:beta.noael_studies dermal absorption 140 mg/kg bw rat dermal 90-day dermal absorption SOURCE_SUBDIR=sccp_o_117; REPORT_TITLE=OPINION ON HC Blue n° 12 COLIPA n° B73; OPINION_NUMBER=SCCP/1135/07; COMMITTEE=Scientific Committee on Consumer Products (SCCP); REPORT_DATE=18 December 2007; VALUE_TEXT=140; DOSE=With a penetration of 1%; this results in a dermal absorption of 5.25 mg per treatment, which is 0.0875 mg/kg bw So a margin of safety of 240 can be calculated between the figure for human exposure to oxidative hair dye and the no adverse effect level found in rats in the 90-day study (limited study, only 1 dose tested).; EFFECT=With a penetration of 1%; this results in a dermal absorption of 5.25 mg per treatment, which is 0.0875 mg/kg bw So a margin of safety of 240 can be calculated between the figure for human exposure to oxidative hair dye and the no adverse effect level found in rats in the 90-day study (limited study, only 1 dose tested). It should be noted that no effects were observed in the teratogenicity study at 140 mg/kg bw. For the semi-permanent hair dye a safety margin of 343 can be calculated. It should be noted that the NOAEL stems from a daily exposure for 90 days, whereas human exposure to permanent hair dye is unlikely to be more frequent than once a month and human exposure to semi-permanent hair dye is unlikely to be more than once a week.” Submission II for HC Blue n° 12 was submitted in December 1993 by COLIPA². The Scientific Committee on Cosmetic products and Non-Food Products intended for Consumers (SCCNFP) adopted at its plenary meeting on 23 June 1999 an opinion (SCCNFP/0140/99) with the conclusion that: “The SCCNFP is o; CITATION_NUMBERS=[]; DETAILS_JSON={"cas_number":"104576-93-0","citation":"","dose":"With a penetration of 1%; this results in a dermal absorption of 5.25 mg per treatment, which is 0.0875 mg/kg bw So a margin of safety of 240 can be calculated between the figure for human exposure to oxidative hair dye and the no adverse effect level found in rats in the 90-day study (limited study, only 1 dose tested).","duration":"90-day","effect":"With a penetration of 1%; this results in a dermal absorption of 5.25 mg per treatment, which is 0.0875 mg/kg bw So a margin of safety of 240 can be calculated between the figure for human exposure to oxidative hair dye and the no adverse effect level found in rats in the 90-day study (limited study, only 1 dose tested). It should be noted that no effects were observed in the teratogenicity study at 140 mg/kg bw. For the semi-permanent hair dye a safety margin of 343 can be calculated. It should be noted that the NOAEL stems from a daily exposure for 90 days, whereas human exposure to permanent hair dye is unlikely to be more frequent than once a month and human exposure to semi-permanent hair dye is unlikely to be more than once a week.” Submission II for HC Blue n° 12 was submitted in December 1993 by COLIPA². The Scientific Committee on Cosmetic products and Non-Food Products intended for Consumers (SCCNFP) adopted at its plenary meeting on 23 June 1999 an opinion (SCCNFP/0140/99) with the conclusion that: “The SCCNFP is o","endpoint":"dermal absorption","ingredient":"HC Blue No. 12","loael_value":"","noael_unit":"mg/kg bw","noael_value":"140","page":5,"route":"dermal","species":"rat","study_id":"sccp_o_117_noael_002"}
UnifiedCodex:SCCS_SHADOW:beta.noael_studies dermal absorption =0.253 mg/kg rat oral 13-week dermal absorption SOURCE_SUBDIR=sccp_o_117; REPORT_TITLE=OPINION ON HC Blue n° 12 COLIPA n° B73; OPINION_NUMBER=SCCP/1135/07; COMMITTEE=Scientific Committee on Consumer Products (SCCP); REPORT_DATE=18 December 2007; VALUE_TEXT== 0.253; DOSE=Safety evaluation (including calculation of the MoS) CALCULATION OF THE MARGIN OF SAFETY (HC Blue n° 12) (oxidative and non-oxidative) Maximum absorption through the skin A (µg/cm2) = 21.7 µg/cm² Skin Area surface SAS (cm2) = 700 cm2 Dermal absorption per treatment SAS x A x 0.001 = 15.19 mg Typical body weight of human = 60 kg Systemic exposure...; EFFECT=icity No data submitted 3.3.11. Human data No data submitted 3.3.12. Special investigations No data submitted 3.3.13. Safety evaluation (including calculation of the MoS) CALCULATION OF THE MARGIN OF SAFETY (HC Blue n° 12) (oxidative and non-oxidative) Maximum absorption through the skin A (µg/cm2) = 21.7 µg/cm² Skin Area surface SAS (cm2) = 700 cm2 Dermal absorption per treatment SAS x A x 0.001 = 15.19 mg Typical body weight of human = 60 kg Systemic exposure dose (SED) SAS x A x 0.001/60 = 0.253 mg/kg No observed adverse effect level NOAEL = 60 mg/kg bw (13-week, oral, rat) Margin of Safety NOAEL / SED = 237 3.3.14. Discussion Physico-chemical properties HC Blue n° 12 is used as a non-reactive hair colouring agent ("Direct Dye") in semi- permanent hair dye formulations at a maximum on-head concentration of 1.5 %, as well as a non-reactive hair colouring agent ("Direct Dye") in oxidative hair dye formulations at a maximum on-head concentration of 0.75 %. HC Blue n° 12 is both a secondary and a tertiary amine and thus is prone to nitrosation; CITATION_NUMBERS=[]; DETAILS_JSON={"cas_number":"104576-93-0","citation":"","dose":"Safety evaluation (including calculation of the MoS) CALCULATION OF THE MARGIN OF SAFETY (HC Blue n° 12) (oxidative and non-oxidative) Maximum absorption through the skin A (µg/cm2) = 21.7 µg/cm² Skin Area surface SAS (cm2) = 700 cm2 Dermal absorption per treatment SAS x A x 0.001 = 15.19 mg Typical body weight of human = 60 kg Systemic exposure...","duration":"13-week","effect":"icity No data submitted 3.3.11. Human data No data submitted 3.3.12. Special investigations No data submitted 3.3.13. Safety evaluation (including calculation of the MoS) CALCULATION OF THE MARGIN OF SAFETY (HC Blue n° 12) (oxidative and non-oxidative) Maximum absorption through the skin A (µg/cm2) = 21.7 µg/cm² Skin Area surface SAS (cm2) = 700 cm2 Dermal absorption per treatment SAS x A x 0.001 = 15.19 mg Typical body weight of human = 60 kg Systemic exposure dose (SED) SAS x A x 0.001/60 = 0.253 mg/kg No observed adverse effect level NOAEL = 60 mg/kg bw (13-week, oral, rat) Margin of Safety NOAEL / SED = 237 3.3.14. Discussion Physico-chemical properties HC Blue n° 12 is used as a non-reactive hair colouring agent (\"Direct Dye\") in semi- permanent hair dye formulations at a maximum on-head concentration of 1.5 %, as well as a non-reactive hair colouring agent (\"Direct Dye\") in oxidative hair dye formulations at a maximum on-head concentration of 0.75 %. HC Blue n° 12 is both a secondary and a tertiary amine and thus is prone to nitrosation","endpoint":"dermal absorption","ingredient":"HC Blue No. 12","loael_value":"","noael_unit":"mg/kg","noael_value":"= 0.253","page":29,"route":"oral","species":"rat","study_id":"sccp_o_117_noael_007"}
UnifiedCodex:SCCS_SHADOW:beta.noael_studies dermal absorption =60 mg/kg bw rat oral 13-week dermal absorption SOURCE_SUBDIR=sccp_o_117; REPORT_TITLE=OPINION ON HC Blue n° 12 COLIPA n° B73; OPINION_NUMBER=SCCP/1135/07; COMMITTEE=Scientific Committee on Consumer Products (SCCP); REPORT_DATE=18 December 2007; VALUE_TEXT== 60; DOSE=Safety evaluation (including calculation of the MoS) CALCULATION OF THE MARGIN OF SAFETY (HC Blue n° 12) (oxidative and non-oxidative) Maximum absorption through the skin A (µg/cm2) = 21.7 µg/cm² Skin Area surface SAS (cm2) = 700 cm2 Dermal absorption per treatment SAS x A x 0.001 = 15.19 mg Typical body weight of human = 60 kg Systemic exposure...; EFFECT=Human data No data submitted 3.3.12. Special investigations No data submitted 3.3.13. Safety evaluation (including calculation of the MoS) CALCULATION OF THE MARGIN OF SAFETY (HC Blue n° 12) (oxidative and non-oxidative) Maximum absorption through the skin A (µg/cm2) = 21.7 µg/cm² Skin Area surface SAS (cm2) = 700 cm2 Dermal absorption per treatment SAS x A x 0.001 = 15.19 mg Typical body weight of human = 60 kg Systemic exposure dose (SED) SAS x A x 0.001/60 = 0.253 mg/kg No observed adverse effect level NOAEL = 60 mg/kg bw (13-week, oral, rat) Margin of Safety NOAEL / SED = 237 3.3.14. Discussion Physico-chemical properties HC Blue n° 12 is used as a non-reactive hair colouring agent ("Direct Dye") in semi- permanent hair dye formulations at a maximum on-head concentration of 1.5 %, as well as a non-reactive hair colouring agent ("Direct Dye") in oxidative hair dye formulations at a maximum on-head concentration of 0.75 %. HC Blue n° 12 is both a secondary and a tertiary amine and thus is prone to nitrosation. It s; CITATION_NUMBERS=[]; DETAILS_JSON={"cas_number":"104576-93-0","citation":"","dose":"Safety evaluation (including calculation of the MoS) CALCULATION OF THE MARGIN OF SAFETY (HC Blue n° 12) (oxidative and non-oxidative) Maximum absorption through the skin A (µg/cm2) = 21.7 µg/cm² Skin Area surface SAS (cm2) = 700 cm2 Dermal absorption per treatment SAS x A x 0.001 = 15.19 mg Typical body weight of human = 60 kg Systemic exposure...","duration":"13-week","effect":"Human data No data submitted 3.3.12. Special investigations No data submitted 3.3.13. Safety evaluation (including calculation of the MoS) CALCULATION OF THE MARGIN OF SAFETY (HC Blue n° 12) (oxidative and non-oxidative) Maximum absorption through the skin A (µg/cm2) = 21.7 µg/cm² Skin Area surface SAS (cm2) = 700 cm2 Dermal absorption per treatment SAS x A x 0.001 = 15.19 mg Typical body weight of human = 60 kg Systemic exposure dose (SED) SAS x A x 0.001/60 = 0.253 mg/kg No observed adverse effect level NOAEL = 60 mg/kg bw (13-week, oral, rat) Margin of Safety NOAEL / SED = 237 3.3.14. Discussion Physico-chemical properties HC Blue n° 12 is used as a non-reactive hair colouring agent (\"Direct Dye\") in semi- permanent hair dye formulations at a maximum on-head concentration of 1.5 %, as well as a non-reactive hair colouring agent (\"Direct Dye\") in oxidative hair dye formulations at a maximum on-head concentration of 0.75 %. HC Blue n° 12 is both a secondary and a tertiary amine and thus is prone to nitrosation. It s","endpoint":"dermal absorption","ingredient":"HC Blue No. 12","loael_value":"","noael_unit":"mg/kg bw","noael_value":"= 60","page":29,"route":"oral","species":"rat","study_id":"sccp_o_117_noael_008"}
UnifiedCodex:SCCS_SHADOW:beta.noael_studies dermal absorption =60 mg/kg bw rat oral 13-week dermal absorption SOURCE_SUBDIR=sccp_o_117; REPORT_TITLE=OPINION ON HC Blue n° 12 COLIPA n° B73; OPINION_NUMBER=SCCP/1135/07; COMMITTEE=Scientific Committee on Consumer Products (SCCP); REPORT_DATE=18 December 2007; VALUE_TEXT== 60; DOSE=Safety evaluation (including calculation of the MoS) CALCULATION OF THE MARGIN OF SAFETY (HC Blue n° 12) (oxidative and non-oxidative) Maximum absorption through the skin A (µg/cm2) = 21.7 µg/cm² Skin Area surface SAS (cm2) = 700 cm2 Dermal absorption per treatment SAS x A x 0.001 = 15.19 mg Typical body weight of human = 60 kg Systemic exposure...; EFFECT=ons No data submitted 3.3.13. Safety evaluation (including calculation of the MoS) CALCULATION OF THE MARGIN OF SAFETY (HC Blue n° 12) (oxidative and non-oxidative) Maximum absorption through the skin A (µg/cm2) = 21.7 µg/cm² Skin Area surface SAS (cm2) = 700 cm2 Dermal absorption per treatment SAS x A x 0.001 = 15.19 mg Typical body weight of human = 60 kg Systemic exposure dose (SED) SAS x A x 0.001/60 = 0.253 mg/kg No observed adverse effect level NOAEL = 60 mg/kg bw (13-week, oral, rat) Margin of Safety NOAEL / SED = 237 3.3.14. Discussion Physico-chemical properties HC Blue n° 12 is used as a non-reactive hair colouring agent ("Direct Dye") in semi- permanent hair dye formulations at a maximum on-head concentration of 1.5 %, as well as a non-reactive hair colouring agent ("Direct Dye") in oxidative hair dye formulations at a maximum on-head concentration of 0.75 %. HC Blue n° 12 is both a secondary and a tertiary amine and thus is prone to nitrosation. It should not be used in combination with nitrosating substance; CITATION_NUMBERS=[]; DETAILS_JSON={"cas_number":"104576-93-0","citation":"","dose":"Safety evaluation (including calculation of the MoS) CALCULATION OF THE MARGIN OF SAFETY (HC Blue n° 12) (oxidative and non-oxidative) Maximum absorption through the skin A (µg/cm2) = 21.7 µg/cm² Skin Area surface SAS (cm2) = 700 cm2 Dermal absorption per treatment SAS x A x 0.001 = 15.19 mg Typical body weight of human = 60 kg Systemic exposure...","duration":"13-week","effect":"ons No data submitted 3.3.13. Safety evaluation (including calculation of the MoS) CALCULATION OF THE MARGIN OF SAFETY (HC Blue n° 12) (oxidative and non-oxidative) Maximum absorption through the skin A (µg/cm2) = 21.7 µg/cm² Skin Area surface SAS (cm2) = 700 cm2 Dermal absorption per treatment SAS x A x 0.001 = 15.19 mg Typical body weight of human = 60 kg Systemic exposure dose (SED) SAS x A x 0.001/60 = 0.253 mg/kg No observed adverse effect level NOAEL = 60 mg/kg bw (13-week, oral, rat) Margin of Safety NOAEL / SED = 237 3.3.14. Discussion Physico-chemical properties HC Blue n° 12 is used as a non-reactive hair colouring agent (\"Direct Dye\") in semi- permanent hair dye formulations at a maximum on-head concentration of 1.5 %, as well as a non-reactive hair colouring agent (\"Direct Dye\") in oxidative hair dye formulations at a maximum on-head concentration of 0.75 %. HC Blue n° 12 is both a secondary and a tertiary amine and thus is prone to nitrosation. It should not be used in combination with nitrosating substance","endpoint":"dermal absorption","ingredient":"HC Blue No. 12","loael_value":"","noael_unit":"mg/kg bw","noael_value":"= 60","page":29,"route":"oral","species":"rat","study_id":"sccp_o_117_noael_009"}
UnifiedCodex:SCCS_SHADOW:beta.noael_studies dermal absorption 140 mg/kg bw rat dermal 90-day dermal absorption SOURCE_SUBDIR=sccp_o_149; REPORT_TITLE=OPINION ON HC Blue n° 12 COLIPA n° B73; OPINION_NUMBER=SCCP/1209/08; COMMITTEE=Scientific Committee on Consumer Products (SCCP); REPORT_DATE=adopted on 18 December 2007; VALUE_TEXT=140; DOSE=With a penetration of 1%; this results in a dermal absorption of 5.25 mg per treatment, which is 0.0875 mg/kg bw So a margin of safety of 240 can be calculated between the figure for human exposure to oxidative hair dye and the no adverse effect level found in rats in the 90-day study (limited study, only 1 dose tested).; EFFECT=With a penetration of 1%; this results in a dermal absorption of 5.25 mg per treatment, which is 0.0875 mg/kg bw So a margin of safety of 240 can be calculated between the figure for human exposure to oxidative hair dye and the no adverse effect level found in rats in the 90-day study (limited study, only 1 dose tested). It should be noted that no effects were observed in the teratogenicity study at 140 mg/kg bw. For the semi-permanent hair dye a safety margin of 343 can be calculated. It should be noted that the NOAEL stems from a daily exposure for 90 days, whereas human exposure to permanent hair dye is unlikely to be more frequent than once a month and human exposure to semi-permanent hair dye is unlikely to be more than once a week.” Submission II for HC Blue n° 12 was submitted in December 1993 by COLIPA². The Scientific Committee on Cosmetic products and Non-Food Products intended for Consumers (SCCNFP) adopted at its plenary meeting on 23 June 1999 an opinion (SCCNFP/0140/99) with the conclusion that: “The SCCNFP is o; CITATION_NUMBERS=[]; DETAILS_JSON={"cas_number":"104576-93-0","citation":"","dose":"With a penetration of 1%; this results in a dermal absorption of 5.25 mg per treatment, which is 0.0875 mg/kg bw So a margin of safety of 240 can be calculated between the figure for human exposure to oxidative hair dye and the no adverse effect level found in rats in the 90-day study (limited study, only 1 dose tested).","duration":"90-day","effect":"With a penetration of 1%; this results in a dermal absorption of 5.25 mg per treatment, which is 0.0875 mg/kg bw So a margin of safety of 240 can be calculated between the figure for human exposure to oxidative hair dye and the no adverse effect level found in rats in the 90-day study (limited study, only 1 dose tested). It should be noted that no effects were observed in the teratogenicity study at 140 mg/kg bw. For the semi-permanent hair dye a safety margin of 343 can be calculated. It should be noted that the NOAEL stems from a daily exposure for 90 days, whereas human exposure to permanent hair dye is unlikely to be more frequent than once a month and human exposure to semi-permanent hair dye is unlikely to be more than once a week.” Submission II for HC Blue n° 12 was submitted in December 1993 by COLIPA². The Scientific Committee on Cosmetic products and Non-Food Products intended for Consumers (SCCNFP) adopted at its plenary meeting on 23 June 1999 an opinion (SCCNFP/0140/99) with the conclusion that: “The SCCNFP is o","endpoint":"dermal absorption","ingredient":"HC Blue No. 12","loael_value":"","noael_unit":"mg/kg bw","noael_value":"140","page":5,"route":"dermal","species":"rat","study_id":"sccp_o_149_noael_002"}
UnifiedCodex:SCCS_SHADOW:beta.noael_studies dermal absorption =0.253 mg/kg rat oral 13-week dermal absorption SOURCE_SUBDIR=sccp_o_149; REPORT_TITLE=OPINION ON HC Blue n° 12 COLIPA n° B73; OPINION_NUMBER=SCCP/1209/08; COMMITTEE=Scientific Committee on Consumer Products (SCCP); REPORT_DATE=adopted on 18 December 2007; VALUE_TEXT== 0.253; DOSE=Safety evaluation (including calculation of the MoS) CALCULATION OF THE MARGIN OF SAFETY (HC Blue n° 12) (oxidative and non-oxidative) Maximum absorption through the skin A (μg/cm2) = 21.7 µg/cm² Skin Area surface SAS (cm2) = 700 cm2 Dermal absorption per treatment SAS x A x 0.001 = 15.19 mg Typical body weight of human = 60 kg Systemic exposure...; EFFECT=on on HC Blue n° 12 29 3.3.11. Human data No data submitted 3.3.12. Special investigations No data submitted 3.3.13. Safety evaluation (including calculation of the MoS) CALCULATION OF THE MARGIN OF SAFETY (HC Blue n° 12) (oxidative and non-oxidative) Maximum absorption through the skin A (μg/cm2) = 21.7 µg/cm² Skin Area surface SAS (cm2) = 700 cm2 Dermal absorption per treatment SAS x A x 0.001 = 15.19 mg Typical body weight of human = 60 kg Systemic exposure dose (SED) SAS x A x 0.001/60 = 0.253 mg/kg No observed adverse effect level NOAEL = 60 mg/kg bw (13-week, oral, rat) Margin of Safety NOAEL / SED = 237 3.3.14. Discussion Physico-chemical properties HC Blue n° 12 is used as a non-reactive hair colouring agent ("Direct Dye") in semi- permanent hair dye formulations at a maximum on-head concentration of 1.5 %, as well as a non-reactive hair colouring agent ("Direct Dye") in oxidative hair dye formulations at a maximum on-head concentration of 0.75 %. HC Blue n° 12 is both a secondary and a tertiary amine and thus is prone to nitrosation; CITATION_NUMBERS=[]; DETAILS_JSON={"cas_number":"104576-93-0","citation":"","dose":"Safety evaluation (including calculation of the MoS) CALCULATION OF THE MARGIN OF SAFETY (HC Blue n° 12) (oxidative and non-oxidative) Maximum absorption through the skin A (μg/cm2) = 21.7 µg/cm² Skin Area surface SAS (cm2) = 700 cm2 Dermal absorption per treatment SAS x A x 0.001 = 15.19 mg Typical body weight of human = 60 kg Systemic exposure...","duration":"13-week","effect":"on on HC Blue n° 12 29 3.3.11. Human data No data submitted 3.3.12. Special investigations No data submitted 3.3.13. Safety evaluation (including calculation of the MoS) CALCULATION OF THE MARGIN OF SAFETY (HC Blue n° 12) (oxidative and non-oxidative) Maximum absorption through the skin A (μg/cm2) = 21.7 µg/cm² Skin Area surface SAS (cm2) = 700 cm2 Dermal absorption per treatment SAS x A x 0.001 = 15.19 mg Typical body weight of human = 60 kg Systemic exposure dose (SED) SAS x A x 0.001/60 = 0.253 mg/kg No observed adverse effect level NOAEL = 60 mg/kg bw (13-week, oral, rat) Margin of Safety NOAEL / SED = 237 3.3.14. Discussion Physico-chemical properties HC Blue n° 12 is used as a non-reactive hair colouring agent (\"Direct Dye\") in semi- permanent hair dye formulations at a maximum on-head concentration of 1.5 %, as well as a non-reactive hair colouring agent (\"Direct Dye\") in oxidative hair dye formulations at a maximum on-head concentration of 0.75 %. HC Blue n° 12 is both a secondary and a tertiary amine and thus is prone to nitrosation","endpoint":"dermal absorption","ingredient":"HC Blue No. 12","loael_value":"","noael_unit":"mg/kg","noael_value":"= 0.253","page":29,"route":"oral","species":"rat","study_id":"sccp_o_149_noael_007"}
UnifiedCodex:SCCS_SHADOW:beta.noael_studies dermal absorption =60 mg/kg bw rat oral 13-week dermal absorption SOURCE_SUBDIR=sccp_o_149; REPORT_TITLE=OPINION ON HC Blue n° 12 COLIPA n° B73; OPINION_NUMBER=SCCP/1209/08; COMMITTEE=Scientific Committee on Consumer Products (SCCP); REPORT_DATE=adopted on 18 December 2007; VALUE_TEXT== 60; DOSE=Safety evaluation (including calculation of the MoS) CALCULATION OF THE MARGIN OF SAFETY (HC Blue n° 12) (oxidative and non-oxidative) Maximum absorption through the skin A (μg/cm2) = 21.7 µg/cm² Skin Area surface SAS (cm2) = 700 cm2 Dermal absorption per treatment SAS x A x 0.001 = 15.19 mg Typical body weight of human = 60 kg Systemic exposure...; EFFECT=Human data No data submitted 3.3.12. Special investigations No data submitted 3.3.13. Safety evaluation (including calculation of the MoS) CALCULATION OF THE MARGIN OF SAFETY (HC Blue n° 12) (oxidative and non-oxidative) Maximum absorption through the skin A (μg/cm2) = 21.7 µg/cm² Skin Area surface SAS (cm2) = 700 cm2 Dermal absorption per treatment SAS x A x 0.001 = 15.19 mg Typical body weight of human = 60 kg Systemic exposure dose (SED) SAS x A x 0.001/60 = 0.253 mg/kg No observed adverse effect level NOAEL = 60 mg/kg bw (13-week, oral, rat) Margin of Safety NOAEL / SED = 237 3.3.14. Discussion Physico-chemical properties HC Blue n° 12 is used as a non-reactive hair colouring agent ("Direct Dye") in semi- permanent hair dye formulations at a maximum on-head concentration of 1.5 %, as well as a non-reactive hair colouring agent ("Direct Dye") in oxidative hair dye formulations at a maximum on-head concentration of 0.75 %. HC Blue n° 12 is both a secondary and a tertiary amine and thus is prone to nitrosation. It s; CITATION_NUMBERS=[]; DETAILS_JSON={"cas_number":"104576-93-0","citation":"","dose":"Safety evaluation (including calculation of the MoS) CALCULATION OF THE MARGIN OF SAFETY (HC Blue n° 12) (oxidative and non-oxidative) Maximum absorption through the skin A (μg/cm2) = 21.7 µg/cm² Skin Area surface SAS (cm2) = 700 cm2 Dermal absorption per treatment SAS x A x 0.001 = 15.19 mg Typical body weight of human = 60 kg Systemic exposure...","duration":"13-week","effect":"Human data No data submitted 3.3.12. Special investigations No data submitted 3.3.13. Safety evaluation (including calculation of the MoS) CALCULATION OF THE MARGIN OF SAFETY (HC Blue n° 12) (oxidative and non-oxidative) Maximum absorption through the skin A (μg/cm2) = 21.7 µg/cm² Skin Area surface SAS (cm2) = 700 cm2 Dermal absorption per treatment SAS x A x 0.001 = 15.19 mg Typical body weight of human = 60 kg Systemic exposure dose (SED) SAS x A x 0.001/60 = 0.253 mg/kg No observed adverse effect level NOAEL = 60 mg/kg bw (13-week, oral, rat) Margin of Safety NOAEL / SED = 237 3.3.14. Discussion Physico-chemical properties HC Blue n° 12 is used as a non-reactive hair colouring agent (\"Direct Dye\") in semi- permanent hair dye formulations at a maximum on-head concentration of 1.5 %, as well as a non-reactive hair colouring agent (\"Direct Dye\") in oxidative hair dye formulations at a maximum on-head concentration of 0.75 %. HC Blue n° 12 is both a secondary and a tertiary amine and thus is prone to nitrosation. It s","endpoint":"dermal absorption","ingredient":"HC Blue No. 12","loael_value":"","noael_unit":"mg/kg bw","noael_value":"= 60","page":29,"route":"oral","species":"rat","study_id":"sccp_o_149_noael_008"}
UnifiedCodex:SCCS_SHADOW:beta.noael_studies dermal absorption =60 mg/kg bw rat oral 13-week dermal absorption SOURCE_SUBDIR=sccp_o_149; REPORT_TITLE=OPINION ON HC Blue n° 12 COLIPA n° B73; OPINION_NUMBER=SCCP/1209/08; COMMITTEE=Scientific Committee on Consumer Products (SCCP); REPORT_DATE=adopted on 18 December 2007; VALUE_TEXT== 60; DOSE=Safety evaluation (including calculation of the MoS) CALCULATION OF THE MARGIN OF SAFETY (HC Blue n° 12) (oxidative and non-oxidative) Maximum absorption through the skin A (μg/cm2) = 21.7 µg/cm² Skin Area surface SAS (cm2) = 700 cm2 Dermal absorption per treatment SAS x A x 0.001 = 15.19 mg Typical body weight of human = 60 kg Systemic exposure...; EFFECT=ons No data submitted 3.3.13. Safety evaluation (including calculation of the MoS) CALCULATION OF THE MARGIN OF SAFETY (HC Blue n° 12) (oxidative and non-oxidative) Maximum absorption through the skin A (μg/cm2) = 21.7 µg/cm² Skin Area surface SAS (cm2) = 700 cm2 Dermal absorption per treatment SAS x A x 0.001 = 15.19 mg Typical body weight of human = 60 kg Systemic exposure dose (SED) SAS x A x 0.001/60 = 0.253 mg/kg No observed adverse effect level NOAEL = 60 mg/kg bw (13-week, oral, rat) Margin of Safety NOAEL / SED = 237 3.3.14. Discussion Physico-chemical properties HC Blue n° 12 is used as a non-reactive hair colouring agent ("Direct Dye") in semi- permanent hair dye formulations at a maximum on-head concentration of 1.5 %, as well as a non-reactive hair colouring agent ("Direct Dye") in oxidative hair dye formulations at a maximum on-head concentration of 0.75 %. HC Blue n° 12 is both a secondary and a tertiary amine and thus is prone to nitrosation. It should not be used in combination with nitrosating substance; CITATION_NUMBERS=[]; DETAILS_JSON={"cas_number":"104576-93-0","citation":"","dose":"Safety evaluation (including calculation of the MoS) CALCULATION OF THE MARGIN OF SAFETY (HC Blue n° 12) (oxidative and non-oxidative) Maximum absorption through the skin A (μg/cm2) = 21.7 µg/cm² Skin Area surface SAS (cm2) = 700 cm2 Dermal absorption per treatment SAS x A x 0.001 = 15.19 mg Typical body weight of human = 60 kg Systemic exposure...","duration":"13-week","effect":"ons No data submitted 3.3.13. Safety evaluation (including calculation of the MoS) CALCULATION OF THE MARGIN OF SAFETY (HC Blue n° 12) (oxidative and non-oxidative) Maximum absorption through the skin A (μg/cm2) = 21.7 µg/cm² Skin Area surface SAS (cm2) = 700 cm2 Dermal absorption per treatment SAS x A x 0.001 = 15.19 mg Typical body weight of human = 60 kg Systemic exposure dose (SED) SAS x A x 0.001/60 = 0.253 mg/kg No observed adverse effect level NOAEL = 60 mg/kg bw (13-week, oral, rat) Margin of Safety NOAEL / SED = 237 3.3.14. Discussion Physico-chemical properties HC Blue n° 12 is used as a non-reactive hair colouring agent (\"Direct Dye\") in semi- permanent hair dye formulations at a maximum on-head concentration of 1.5 %, as well as a non-reactive hair colouring agent (\"Direct Dye\") in oxidative hair dye formulations at a maximum on-head concentration of 0.75 %. HC Blue n° 12 is both a secondary and a tertiary amine and thus is prone to nitrosation. It should not be used in combination with nitrosating substance","endpoint":"dermal absorption","ingredient":"HC Blue No. 12","loael_value":"","noael_unit":"mg/kg bw","noael_value":"= 60","page":29,"route":"oral","species":"rat","study_id":"sccp_o_149_noael_009"}
UnifiedCodex:SCCS_SHADOW:beta.noael_studies developmental toxicity 140 mg/kg bw/d human - developmental developmental toxicity SOURCE_SUBDIR=sccp_o_117; REPORT_TITLE=OPINION ON HC Blue n° 12 COLIPA n° B73; OPINION_NUMBER=SCCP/1135/07; COMMITTEE=Scientific Committee on Consumer Products (SCCP); REPORT_DATE=18 December 2007; VALUE_TEXT=140; DOSE=Results With the exception of violet staining of urine (all treated animals) and fur, paw and tail (high dose group) no clinical signs were noted.; EFFECT=mperfections and the remainder was subjected to skeletal examination. Results With the exception of violet staining of urine (all treated animals) and fur, paw and tail (high dose group) no clinical signs were noted. Food consumption and body weight changes of the dams were not significantly different from controls. Foetal weight, sex ratio, placental weight, number of resorptions and corpora lutea were not influenced by treatment. Examination of skeleton and viscera revealed no relevant findings. Conclusion The NOAEL of maternal and developmental toxicity in this study is 140 mg/kg bw/d. Ref.: 34 Comment The highest dose of 140 mg/kg bw is too low for hazard assessment. For this, the highest dose used should be 1000 mg/kg bw and should induce toxicity. 3.3.9. Toxicokinetics 3.3.9.1. Toxicokinetics in vitro Bioavailability across intestinal barrier in TC-7 (human intestinal epithelial) cells Guideline: / Cells: Human intestinal epithelial cell line TC-7 Test substance: HC Blue n° 12 Batch: 29/30 Purity: 93.9 area% (HPLC) T; CITATION=Ref.: 34 Comment The highest dose of 140 mg/kg bw is too low for hazard assessment; CITATION_NUMBERS=[34,140]; REFERENCE=Ref.: 34 Comment The highest dose of 140 mg/kg bw is too low for hazard assessment; DETAILS_JSON={"cas_number":"104576-93-0","citation":"Ref.: 34 Comment The highest dose of 140 mg/kg bw is too low for hazard assessment","dose":"Results With the exception of violet staining of urine (all treated animals) and fur, paw and tail (high dose group) no clinical signs were noted.","duration":"developmental","effect":"mperfections and the remainder was subjected to skeletal examination. Results With the exception of violet staining of urine (all treated animals) and fur, paw and tail (high dose group) no clinical signs were noted. Food consumption and body weight changes of the dams were not significantly different from controls. Foetal weight, sex ratio, placental weight, number of resorptions and corpora lutea were not influenced by treatment. Examination of skeleton and viscera revealed no relevant findings. Conclusion The NOAEL of maternal and developmental toxicity in this study is 140 mg/kg bw/d. Ref.: 34 Comment The highest dose of 140 mg/kg bw is too low for hazard assessment. For this, the highest dose used should be 1000 mg/kg bw and should induce toxicity. 3.3.9. Toxicokinetics 3.3.9.1. Toxicokinetics in vitro Bioavailability across intestinal barrier in TC-7 (human intestinal epithelial) cells Guideline: / Cells: Human intestinal epithelial cell line TC-7 Test substance: HC Blue n° 12 Batch: 29/30 Purity: 93.9 area% (HPLC) T","endpoint":"developmental toxicity","ingredient":"HC Blue No. 12","loael_value":"","noael_unit":"mg/kg bw/d","noael_value":"140","page":27,"route":"","species":"human","study_id":"sccp_o_117_noael_006"}
UnifiedCodex:SCCS_SHADOW:beta.noael_studies developmental toxicity 140 mg/kg bw/d human - developmental developmental toxicity SOURCE_SUBDIR=sccp_o_149; REPORT_TITLE=OPINION ON HC Blue n° 12 COLIPA n° B73; OPINION_NUMBER=SCCP/1209/08; COMMITTEE=Scientific Committee on Consumer Products (SCCP); REPORT_DATE=adopted on 18 December 2007; VALUE_TEXT=140; DOSE=Results With the exception of violet staining of urine (all treated animals) and fur, paw and tail (high dose group) no clinical signs were noted.; EFFECT=mperfections and the remainder was subjected to skeletal examination. Results With the exception of violet staining of urine (all treated animals) and fur, paw and tail (high dose group) no clinical signs were noted. Food consumption and body weight changes of the dams were not significantly different from controls. Foetal weight, sex ratio, placental weight, number of resorptions and corpora lutea were not influenced by treatment. Examination of skeleton and viscera revealed no relevant findings. Conclusion The NOAEL of maternal and developmental toxicity in this study is 140 mg/kg bw/d. Ref.: 34 Comment The highest dose of 140 mg/kg bw is too low for hazard assessment. For this, the highest dose used should be 1000 mg/kg bw and should induce toxicity. 3.3.9. Toxicokinetics 3.3.9.1. Toxicokinetics in vitro Bioavailability across intestinal barrier in TC-7 (human intestinal epithelial) cells Guideline: / Cells: Human intestinal epithelial cell line TC-7 Test substance: HC Blue n° 12 Batch: 29/30 Purity: 93.9 area% (HPLC) T; CITATION=Ref.: 34 Comment The highest dose of 140 mg/kg bw is too low for hazard assessment; CITATION_NUMBERS=[34,140]; REFERENCE=Ref.: 34 Comment The highest dose of 140 mg/kg bw is too low for hazard assessment; DETAILS_JSON={"cas_number":"104576-93-0","citation":"Ref.: 34 Comment The highest dose of 140 mg/kg bw is too low for hazard assessment","dose":"Results With the exception of violet staining of urine (all treated animals) and fur, paw and tail (high dose group) no clinical signs were noted.","duration":"developmental","effect":"mperfections and the remainder was subjected to skeletal examination. Results With the exception of violet staining of urine (all treated animals) and fur, paw and tail (high dose group) no clinical signs were noted. Food consumption and body weight changes of the dams were not significantly different from controls. Foetal weight, sex ratio, placental weight, number of resorptions and corpora lutea were not influenced by treatment. Examination of skeleton and viscera revealed no relevant findings. Conclusion The NOAEL of maternal and developmental toxicity in this study is 140 mg/kg bw/d. Ref.: 34 Comment The highest dose of 140 mg/kg bw is too low for hazard assessment. For this, the highest dose used should be 1000 mg/kg bw and should induce toxicity. 3.3.9. Toxicokinetics 3.3.9.1. Toxicokinetics in vitro Bioavailability across intestinal barrier in TC-7 (human intestinal epithelial) cells Guideline: / Cells: Human intestinal epithelial cell line TC-7 Test substance: HC Blue n° 12 Batch: 29/30 Purity: 93.9 area% (HPLC) T","endpoint":"developmental toxicity","ingredient":"HC Blue No. 12","loael_value":"","noael_unit":"mg/kg bw/d","noael_value":"140","page":27,"route":"","species":"human","study_id":"sccp_o_149_noael_006"}
UnifiedCodex:SCCS_SHADOW:beta.noael_studies irritation 30 mg/kg bw rat oral 90-day irritation SOURCE_SUBDIR=sccp_o_117; REPORT_TITLE=OPINION ON HC Blue n° 12 COLIPA n° B73; OPINION_NUMBER=SCCP/1135/07; COMMITTEE=Scientific Committee on Consumer Products (SCCP); REPORT_DATE=18 December 2007; VALUE_TEXT=30; DOSE=In the 90-day study with rats, 30 mg/kg bw was considered to be the NOAEL.; EFFECT=e, earlier called Nitroblau, was submitted in March 1992 by COLIPA1, 2. The Scientific Committee on Cosmetology (SCC) adopted at its 53rd plenary meeting on 25 June 1993 an opinion (SPC/1077/93) with the final conclusion that: “Nitroblau was found moderately toxic in the acute oral toxicity test and slightly toxic after dermal administration to rabbits. Nitroblau showed no signs of irritation. The sensitization test was carried out inadequately. In the 90-day study with rats, 30 mg/kg bw was considered to be the NOAEL. In the teratogenicity study, no irreversible structural changes were observed in the foetuses of the rat, after administration of 140 mg/kg bw. Nitroblau is not genotoxic. The cutaneous absorption was 1% of the administered 14C for the hair dyeing formulation. For normal use of hair dye, the following calculation can be made: 750 mg nitroblau comes in contact with the human skin in permanent hair dye condition (based on a usage volume of 100 ml containing 0.75% nitroblau). With a maximal penetration of 1%, this r; CITATION_NUMBERS=[]; DETAILS_JSON={"cas_number":"104576-93-0","citation":"","dose":"In the 90-day study with rats, 30 mg/kg bw was considered to be the NOAEL.","duration":"90-day","effect":"e, earlier called Nitroblau, was submitted in March 1992 by COLIPA1, 2. The Scientific Committee on Cosmetology (SCC) adopted at its 53rd plenary meeting on 25 June 1993 an opinion (SPC/1077/93) with the final conclusion that: “Nitroblau was found moderately toxic in the acute oral toxicity test and slightly toxic after dermal administration to rabbits. Nitroblau showed no signs of irritation. The sensitization test was carried out inadequately. In the 90-day study with rats, 30 mg/kg bw was considered to be the NOAEL. In the teratogenicity study, no irreversible structural changes were observed in the foetuses of the rat, after administration of 140 mg/kg bw. Nitroblau is not genotoxic. The cutaneous absorption was 1% of the administered 14C for the hair dyeing formulation. For normal use of hair dye, the following calculation can be made: 750 mg nitroblau comes in contact with the human skin in permanent hair dye condition (based on a usage volume of 100 ml containing 0.75% nitroblau). With a maximal penetration of 1%, this r","endpoint":"irritation","ingredient":"HC Blue No. 12","loael_value":"","noael_unit":"mg/kg bw","noael_value":"30","page":5,"route":"oral","species":"rat","study_id":"sccp_o_117_noael_001"}
UnifiedCodex:SCCS_SHADOW:beta.noael_studies irritation 30 mg/kg bw rat oral 90-day irritation SOURCE_SUBDIR=sccp_o_149; REPORT_TITLE=OPINION ON HC Blue n° 12 COLIPA n° B73; OPINION_NUMBER=SCCP/1209/08; COMMITTEE=Scientific Committee on Consumer Products (SCCP); REPORT_DATE=adopted on 18 December 2007; VALUE_TEXT=30; DOSE=In the 90-day study with rats, 30 mg/kg bw was considered to be the NOAEL.; EFFECT=e, earlier called Nitroblau, was submitted in March 1992 by COLIPA1, 2. The Scientific Committee on Cosmetology (SCC) adopted at its 53rd plenary meeting on 25 June 1993 an opinion (SPC/1077/93) with the final conclusion that: “Nitroblau was found moderately toxic in the acute oral toxicity test and slightly toxic after dermal administration to rabbits. Nitroblau showed no signs of irritation. The sensitization test was carried out inadequately. In the 90-day study with rats, 30 mg/kg bw was considered to be the NOAEL. In the teratogenicity study, no irreversible structural changes were observed in the foetuses of the rat, after administration of 140 mg/kg bw. Nitroblau is not genotoxic. The cutaneous absorption was 1% of the administered 14C for the hair dyeing formulation. For normal use of hair dye, the following calculation can be made: 750 mg nitroblau comes in contact with the human skin in permanent hair dye condition (based on a usage volume of 100 ml containing 0.75% nitroblau). With a maximal penetration of 1%, this r; CITATION_NUMBERS=[]; DETAILS_JSON={"cas_number":"104576-93-0","citation":"","dose":"In the 90-day study with rats, 30 mg/kg bw was considered to be the NOAEL.","duration":"90-day","effect":"e, earlier called Nitroblau, was submitted in March 1992 by COLIPA1, 2. The Scientific Committee on Cosmetology (SCC) adopted at its 53rd plenary meeting on 25 June 1993 an opinion (SPC/1077/93) with the final conclusion that: “Nitroblau was found moderately toxic in the acute oral toxicity test and slightly toxic after dermal administration to rabbits. Nitroblau showed no signs of irritation. The sensitization test was carried out inadequately. In the 90-day study with rats, 30 mg/kg bw was considered to be the NOAEL. In the teratogenicity study, no irreversible structural changes were observed in the foetuses of the rat, after administration of 140 mg/kg bw. Nitroblau is not genotoxic. The cutaneous absorption was 1% of the administered 14C for the hair dyeing formulation. For normal use of hair dye, the following calculation can be made: 750 mg nitroblau comes in contact with the human skin in permanent hair dye condition (based on a usage volume of 100 ml containing 0.75% nitroblau). With a maximal penetration of 1%, this r","endpoint":"irritation","ingredient":"HC Blue No. 12","loael_value":"","noael_unit":"mg/kg bw","noael_value":"30","page":5,"route":"oral","species":"rat","study_id":"sccp_o_149_noael_001"}
UnifiedCodex:SCCS_SHADOW:beta.noael_studies repeated dose toxicity 60 mg/kg bw/d - - sub-chronic repeated dose toxicity SOURCE_SUBDIR=sccp_o_117; REPORT_TITLE=OPINION ON HC Blue n° 12 COLIPA n° B73; OPINION_NUMBER=SCCP/1135/07; COMMITTEE=Scientific Committee on Consumer Products (SCCP); REPORT_DATE=18 December 2007; VALUE_TEXT=60; DOSE=Conclusion Under the conditions of the study the tested dose of 30 mg/kg bw/d was found as not exerting systemic toxicity.; EFFECT=and water consumption and body weight gain were in the physiological range and no treatment related changes were noted. Also neither haematology, biochemistry or urinalysis revealed test substance related changes. The histomorphological investigation revealed no substance-related alterations. Conclusion Under the conditions of the study the tested dose of 30 mg/kg bw/d was found as not exerting systemic toxicity. Ref.: 24, 25 Comment of the SCCP on sub-chronic toxicity The dose of 60 mg/kg bw/d is considered the NOAEL dose of subchronic toxicity. 3.3.5.3. Chronic (> 12 months) toxicity No data submitted 3.3.6. Mutagenicity / Genotoxicity 3.3.6.1 Mutagenicity / Genotoxicity in vitro Bacterial Reverse Mutation Test Guideline: OECD 471 Species/strain: Salmonella typhimurium TA98, TA100, TA1535, TA1537 and TA1538 Replicates: 3 replicates in 2 individual experiments both in the presence and absence of S9-mix Test substance: GHS 111183 Solvent: DMSO Batch nr: 13/2/1 Purity: 96.9% NMR, 99.5% HPLC Concentrations: 8 - 5000 µg/plat; CITATION=Ref.: 24, 25 Comment of the SCCP on sub-chronic toxicity The dose of 60 mg/kg bw/d is considered the NOAEL dose of subchronic toxicity; CITATION_NUMBERS=[24,25,60]; REFERENCE=Ref.: 24, 25 Comment of the SCCP on sub-chronic toxicity The dose of 60 mg/kg bw/d is considered the NOAEL dose of subchronic toxicity; DETAILS_JSON={"cas_number":"104576-93-0","citation":"Ref.: 24, 25 Comment of the SCCP on sub-chronic toxicity The dose of 60 mg/kg bw/d is considered the NOAEL dose of subchronic toxicity","dose":"Conclusion Under the conditions of the study the tested dose of 30 mg/kg bw/d was found as not exerting systemic toxicity.","duration":"sub-chronic","effect":"and water consumption and body weight gain were in the physiological range and no treatment related changes were noted. Also neither haematology, biochemistry or urinalysis revealed test substance related changes. The histomorphological investigation revealed no substance-related alterations. Conclusion Under the conditions of the study the tested dose of 30 mg/kg bw/d was found as not exerting systemic toxicity. Ref.: 24, 25 Comment of the SCCP on sub-chronic toxicity The dose of 60 mg/kg bw/d is considered the NOAEL dose of subchronic toxicity. 3.3.5.3. Chronic (> 12 months) toxicity No data submitted 3.3.6. Mutagenicity / Genotoxicity 3.3.6.1 Mutagenicity / Genotoxicity in vitro Bacterial Reverse Mutation Test Guideline: OECD 471 Species/strain: Salmonella typhimurium TA98, TA100, TA1535, TA1537 and TA1538 Replicates: 3 replicates in 2 individual experiments both in the presence and absence of S9-mix Test substance: GHS 111183 Solvent: DMSO Batch nr: 13/2/1 Purity: 96.9% NMR, 99.5% HPLC Concentrations: 8 - 5000 µg/plat","endpoint":"repeated dose toxicity","ingredient":"HC Blue No. 12","loael_value":"","noael_unit":"mg/kg bw/d","noael_value":"60","page":20,"route":"","species":"","study_id":"sccp_o_117_noael_005"}
UnifiedCodex:SCCS_SHADOW:beta.noael_studies repeated dose toxicity 1668 mg/kg bw rat - 28 day repeated dose toxicity SOURCE_SUBDIR=sccp_o_117; REPORT_TITLE=OPINION ON HC Blue n° 12 COLIPA n° B73; OPINION_NUMBER=SCCP/1135/07; COMMITTEE=Scientific Committee on Consumer Products (SCCP); REPORT_DATE=18 December 2007; VALUE_TEXT=1668 to 1775; DOSE=General toxicity In acute toxicity studies in mice and rats, based on the mortality rates LD50 figures from 1668 to 1775 mg/kg bw were calculated.; EFFECT=hair dye formulations at a maximum on-head concentration of 0.75 %. HC Blue n° 12 is both a secondary and a tertiary amine and thus is prone to nitrosation. It should not be used in combination with nitrosating substances. The nitrosamine content should be < 50 ppb. No data submitted for the stability of the test substance in solutions or in the marketed products. General toxicity In acute toxicity studies in mice and rats, based on the mortality rates LD50 figures from 1668 to 1775 mg/kg bw were calculated. The NOAEL of the 28 day toxicity study is 316 mg/kg bw/d. The dose of 60 mg/kg bw/d is considered the NOAEL dose of subchronic toxicity. The NOAEL of maternal and developmental toxicity is 140 mg/kg bw/d. Irritation / sensitisation Undiluted HC Blue n° 12 did not cause any signs of skin irritation in the rabbit. Under the conditions of the test, undiluted HC Blue n° 12 caused transient eye irritation in rabbits.; CITATION_NUMBERS=[]; DETAILS_JSON={"cas_number":"104576-93-0","citation":"","dose":"General toxicity In acute toxicity studies in mice and rats, based on the mortality rates LD50 figures from 1668 to 1775 mg/kg bw were calculated.","duration":"28 day","effect":"hair dye formulations at a maximum on-head concentration of 0.75 %. HC Blue n° 12 is both a secondary and a tertiary amine and thus is prone to nitrosation. It should not be used in combination with nitrosating substances. The nitrosamine content should be < 50 ppb. No data submitted for the stability of the test substance in solutions or in the marketed products. General toxicity In acute toxicity studies in mice and rats, based on the mortality rates LD50 figures from 1668 to 1775 mg/kg bw were calculated. The NOAEL of the 28 day toxicity study is 316 mg/kg bw/d. The dose of 60 mg/kg bw/d is considered the NOAEL dose of subchronic toxicity. The NOAEL of maternal and developmental toxicity is 140 mg/kg bw/d. Irritation / sensitisation Undiluted HC Blue n° 12 did not cause any signs of skin irritation in the rabbit. Under the conditions of the test, undiluted HC Blue n° 12 caused transient eye irritation in rabbits.","endpoint":"repeated dose toxicity","ingredient":"HC Blue No. 12","loael_value":"","noael_unit":"mg/kg bw","noael_value":"1668 to 1775","page":29,"route":"","species":"rat","study_id":"sccp_o_117_noael_010"}
UnifiedCodex:SCCS_SHADOW:beta.noael_studies repeated dose toxicity 60 mg/kg bw/d rat - 28 day repeated dose toxicity SOURCE_SUBDIR=sccp_o_117; REPORT_TITLE=OPINION ON HC Blue n° 12 COLIPA n° B73; OPINION_NUMBER=SCCP/1135/07; COMMITTEE=Scientific Committee on Consumer Products (SCCP); REPORT_DATE=18 December 2007; VALUE_TEXT=60; DOSE=General toxicity In acute toxicity studies in mice and rats, based on the mortality rates LD50 figures from 1668 to 1775 mg/kg bw were calculated.; EFFECT=ary and a tertiary amine and thus is prone to nitrosation. It should not be used in combination with nitrosating substances. The nitrosamine content should be < 50 ppb. No data submitted for the stability of the test substance in solutions or in the marketed products. General toxicity In acute toxicity studies in mice and rats, based on the mortality rates LD50 figures from 1668 to 1775 mg/kg bw were calculated. The NOAEL of the 28 day toxicity study is 316 mg/kg bw/d. The dose of 60 mg/kg bw/d is considered the NOAEL dose of subchronic toxicity. The NOAEL of maternal and developmental toxicity is 140 mg/kg bw/d. Irritation / sensitisation Undiluted HC Blue n° 12 did not cause any signs of skin irritation in the rabbit. Under the conditions of the test, undiluted HC Blue n° 12 caused transient eye irritation in rabbits.; CITATION_NUMBERS=[]; DETAILS_JSON={"cas_number":"104576-93-0","citation":"","dose":"General toxicity In acute toxicity studies in mice and rats, based on the mortality rates LD50 figures from 1668 to 1775 mg/kg bw were calculated.","duration":"28 day","effect":"ary and a tertiary amine and thus is prone to nitrosation. It should not be used in combination with nitrosating substances. The nitrosamine content should be < 50 ppb. No data submitted for the stability of the test substance in solutions or in the marketed products. General toxicity In acute toxicity studies in mice and rats, based on the mortality rates LD50 figures from 1668 to 1775 mg/kg bw were calculated. The NOAEL of the 28 day toxicity study is 316 mg/kg bw/d. The dose of 60 mg/kg bw/d is considered the NOAEL dose of subchronic toxicity. The NOAEL of maternal and developmental toxicity is 140 mg/kg bw/d. Irritation / sensitisation Undiluted HC Blue n° 12 did not cause any signs of skin irritation in the rabbit. Under the conditions of the test, undiluted HC Blue n° 12 caused transient eye irritation in rabbits.","endpoint":"repeated dose toxicity","ingredient":"HC Blue No. 12","loael_value":"","noael_unit":"mg/kg bw/d","noael_value":"60","page":29,"route":"","species":"rat","study_id":"sccp_o_117_noael_011"}
UnifiedCodex:SCCS_SHADOW:beta.noael_studies repeated dose toxicity 140 mg/kg bw/d rat - 28 day repeated dose toxicity SOURCE_SUBDIR=sccp_o_117; REPORT_TITLE=OPINION ON HC Blue n° 12 COLIPA n° B73; OPINION_NUMBER=SCCP/1135/07; COMMITTEE=Scientific Committee on Consumer Products (SCCP); REPORT_DATE=18 December 2007; VALUE_TEXT=140; DOSE=General toxicity In acute toxicity studies in mice and rats, based on the mortality rates LD50 figures from 1668 to 1775 mg/kg bw were calculated.; EFFECT=one to nitrosation. It should not be used in combination with nitrosating substances. The nitrosamine content should be < 50 ppb. No data submitted for the stability of the test substance in solutions or in the marketed products. General toxicity In acute toxicity studies in mice and rats, based on the mortality rates LD50 figures from 1668 to 1775 mg/kg bw were calculated. The NOAEL of the 28 day toxicity study is 316 mg/kg bw/d. The dose of 60 mg/kg bw/d is considered the NOAEL dose of subchronic toxicity. The NOAEL of maternal and developmental toxicity is 140 mg/kg bw/d. Irritation / sensitisation Undiluted HC Blue n° 12 did not cause any signs of skin irritation in the rabbit. Under the conditions of the test, undiluted HC Blue n° 12 caused transient eye irritation in rabbits.; CITATION_NUMBERS=[]; DETAILS_JSON={"cas_number":"104576-93-0","citation":"","dose":"General toxicity In acute toxicity studies in mice and rats, based on the mortality rates LD50 figures from 1668 to 1775 mg/kg bw were calculated.","duration":"28 day","effect":"one to nitrosation. It should not be used in combination with nitrosating substances. The nitrosamine content should be < 50 ppb. No data submitted for the stability of the test substance in solutions or in the marketed products. General toxicity In acute toxicity studies in mice and rats, based on the mortality rates LD50 figures from 1668 to 1775 mg/kg bw were calculated. The NOAEL of the 28 day toxicity study is 316 mg/kg bw/d. The dose of 60 mg/kg bw/d is considered the NOAEL dose of subchronic toxicity. The NOAEL of maternal and developmental toxicity is 140 mg/kg bw/d. Irritation / sensitisation Undiluted HC Blue n° 12 did not cause any signs of skin irritation in the rabbit. Under the conditions of the test, undiluted HC Blue n° 12 caused transient eye irritation in rabbits.","endpoint":"repeated dose toxicity","ingredient":"HC Blue No. 12","loael_value":"","noael_unit":"mg/kg bw/d","noael_value":"140","page":29,"route":"","species":"rat","study_id":"sccp_o_117_noael_012"}
UnifiedCodex:SCCS_SHADOW:beta.noael_studies repeated dose toxicity 60 mg/kg bw/d - - sub-chronic repeated dose toxicity SOURCE_SUBDIR=sccp_o_149; REPORT_TITLE=OPINION ON HC Blue n° 12 COLIPA n° B73; OPINION_NUMBER=SCCP/1209/08; COMMITTEE=Scientific Committee on Consumer Products (SCCP); REPORT_DATE=adopted on 18 December 2007; VALUE_TEXT=60; DOSE=Conclusion Under the conditions of the study the tested dose of 30 mg/kg bw/d was found as not exerting systemic toxicity.; EFFECT=and water consumption and body weight gain were in the physiological range and no treatment related changes were noted. Also neither haematology, biochemistry or urinalysis revealed test substance related changes. The histomorphological investigation revealed no substance-related alterations. Conclusion Under the conditions of the study the tested dose of 30 mg/kg bw/d was found as not exerting systemic toxicity. Ref.: 24, 25 Comment of the SCCP on sub-chronic toxicity The dose of 60 mg/kg bw/d is considered the NOAEL dose of subchronic toxicity. 3.3.5.3. Chronic (> 12 months) toxicity No data submitted 3.3.6. Mutagenicity / Genotoxicity 3.3.6.1 Mutagenicity / Genotoxicity in vitro Bacterial Reverse Mutation Test Guideline: OECD 471 Species/strain: Salmonella typhimurium TA98, TA100, TA1535, TA1537 and TA1538 Replicates: 3 replicates in 2 individual experiments both in the presence and absence of S9-mix Test substance: GHS 111183 Solvent: DMSO Batch nr: 13/2/1 Purity: 96.9% NMR, 99.5% HPLC Concentrations: 8 - 5000 μg/plat; CITATION=Ref.: 24, 25 Comment of the SCCP on sub-chronic toxicity The dose of 60 mg/kg bw/d is considered the NOAEL dose of subchronic toxicity; CITATION_NUMBERS=[24,25,60]; REFERENCE=Ref.: 24, 25 Comment of the SCCP on sub-chronic toxicity The dose of 60 mg/kg bw/d is considered the NOAEL dose of subchronic toxicity; DETAILS_JSON={"cas_number":"104576-93-0","citation":"Ref.: 24, 25 Comment of the SCCP on sub-chronic toxicity The dose of 60 mg/kg bw/d is considered the NOAEL dose of subchronic toxicity","dose":"Conclusion Under the conditions of the study the tested dose of 30 mg/kg bw/d was found as not exerting systemic toxicity.","duration":"sub-chronic","effect":"and water consumption and body weight gain were in the physiological range and no treatment related changes were noted. Also neither haematology, biochemistry or urinalysis revealed test substance related changes. The histomorphological investigation revealed no substance-related alterations. Conclusion Under the conditions of the study the tested dose of 30 mg/kg bw/d was found as not exerting systemic toxicity. Ref.: 24, 25 Comment of the SCCP on sub-chronic toxicity The dose of 60 mg/kg bw/d is considered the NOAEL dose of subchronic toxicity. 3.3.5.3. Chronic (> 12 months) toxicity No data submitted 3.3.6. Mutagenicity / Genotoxicity 3.3.6.1 Mutagenicity / Genotoxicity in vitro Bacterial Reverse Mutation Test Guideline: OECD 471 Species/strain: Salmonella typhimurium TA98, TA100, TA1535, TA1537 and TA1538 Replicates: 3 replicates in 2 individual experiments both in the presence and absence of S9-mix Test substance: GHS 111183 Solvent: DMSO Batch nr: 13/2/1 Purity: 96.9% NMR, 99.5% HPLC Concentrations: 8 - 5000 μg/plat","endpoint":"repeated dose toxicity","ingredient":"HC Blue No. 12","loael_value":"","noael_unit":"mg/kg bw/d","noael_value":"60","page":20,"route":"","species":"","study_id":"sccp_o_149_noael_005"}
UnifiedCodex:SCCS_SHADOW:beta.noael_studies repeated dose toxicity 1668 mg/kg bw rat dermal 28 day repeated dose toxicity SOURCE_SUBDIR=sccp_o_149; REPORT_TITLE=OPINION ON HC Blue n° 12 COLIPA n° B73; OPINION_NUMBER=SCCP/1209/08; COMMITTEE=Scientific Committee on Consumer Products (SCCP); REPORT_DATE=adopted on 18 December 2007; VALUE_TEXT=1668 to 1775; DOSE=General toxicity In acute toxicity studies in mice and rats, based on the mortality rates LD50 figures from 1668 to 1775 mg/kg bw were calculated.; EFFECT=hair dye formulations at a maximum on-head concentration of 0.75 %. HC Blue n° 12 is both a secondary and a tertiary amine and thus is prone to nitrosation. It should not be used in combination with nitrosating substances. The nitrosamine content should be < 50 ppb. No data submitted for the stability of the test substance in solutions or in the marketed products. General toxicity In acute toxicity studies in mice and rats, based on the mortality rates LD50 figures from 1668 to 1775 mg/kg bw were calculated. The NOAEL of the 28 day toxicity study is 316 mg/kg bw/d. The dose of 60 mg/kg bw/d is considered the NOAEL dose of subchronic toxicity. The NOAEL of maternal and developmental toxicity is 140 mg/kg bw/d. Irritation / sensitisation Undiluted HC Blue n° 12 did not cause any signs of skin irritation in the rabbit. Under the conditions of the test, undiluted HC Blue n° 12 caused transient eye irritation in rabbits. In local lymph node assay, the test substance was considered to be a moderate skin sensitising agent. Dermal; CITATION_NUMBERS=[]; DETAILS_JSON={"cas_number":"104576-93-0","citation":"","dose":"General toxicity In acute toxicity studies in mice and rats, based on the mortality rates LD50 figures from 1668 to 1775 mg/kg bw were calculated.","duration":"28 day","effect":"hair dye formulations at a maximum on-head concentration of 0.75 %. HC Blue n° 12 is both a secondary and a tertiary amine and thus is prone to nitrosation. It should not be used in combination with nitrosating substances. The nitrosamine content should be < 50 ppb. No data submitted for the stability of the test substance in solutions or in the marketed products. General toxicity In acute toxicity studies in mice and rats, based on the mortality rates LD50 figures from 1668 to 1775 mg/kg bw were calculated. The NOAEL of the 28 day toxicity study is 316 mg/kg bw/d. The dose of 60 mg/kg bw/d is considered the NOAEL dose of subchronic toxicity. The NOAEL of maternal and developmental toxicity is 140 mg/kg bw/d. Irritation / sensitisation Undiluted HC Blue n° 12 did not cause any signs of skin irritation in the rabbit. Under the conditions of the test, undiluted HC Blue n° 12 caused transient eye irritation in rabbits. In local lymph node assay, the test substance was considered to be a moderate skin sensitising agent. Dermal","endpoint":"repeated dose toxicity","ingredient":"HC Blue No. 12","loael_value":"","noael_unit":"mg/kg bw","noael_value":"1668 to 1775","page":29,"route":"dermal","species":"rat","study_id":"sccp_o_149_noael_010"}
UnifiedCodex:SCCS_SHADOW:beta.noael_studies repeated dose toxicity 60 mg/kg bw/d rat dermal 28 day repeated dose toxicity SOURCE_SUBDIR=sccp_o_149; REPORT_TITLE=OPINION ON HC Blue n° 12 COLIPA n° B73; OPINION_NUMBER=SCCP/1209/08; COMMITTEE=Scientific Committee on Consumer Products (SCCP); REPORT_DATE=adopted on 18 December 2007; VALUE_TEXT=60; DOSE=General toxicity In acute toxicity studies in mice and rats, based on the mortality rates LD50 figures from 1668 to 1775 mg/kg bw were calculated.; EFFECT=ary and a tertiary amine and thus is prone to nitrosation. It should not be used in combination with nitrosating substances. The nitrosamine content should be < 50 ppb. No data submitted for the stability of the test substance in solutions or in the marketed products. General toxicity In acute toxicity studies in mice and rats, based on the mortality rates LD50 figures from 1668 to 1775 mg/kg bw were calculated. The NOAEL of the 28 day toxicity study is 316 mg/kg bw/d. The dose of 60 mg/kg bw/d is considered the NOAEL dose of subchronic toxicity. The NOAEL of maternal and developmental toxicity is 140 mg/kg bw/d. Irritation / sensitisation Undiluted HC Blue n° 12 did not cause any signs of skin irritation in the rabbit. Under the conditions of the test, undiluted HC Blue n° 12 caused transient eye irritation in rabbits. In local lymph node assay, the test substance was considered to be a moderate skin sensitising agent. Dermal absorption; CITATION_NUMBERS=[]; DETAILS_JSON={"cas_number":"104576-93-0","citation":"","dose":"General toxicity In acute toxicity studies in mice and rats, based on the mortality rates LD50 figures from 1668 to 1775 mg/kg bw were calculated.","duration":"28 day","effect":"ary and a tertiary amine and thus is prone to nitrosation. It should not be used in combination with nitrosating substances. The nitrosamine content should be < 50 ppb. No data submitted for the stability of the test substance in solutions or in the marketed products. General toxicity In acute toxicity studies in mice and rats, based on the mortality rates LD50 figures from 1668 to 1775 mg/kg bw were calculated. The NOAEL of the 28 day toxicity study is 316 mg/kg bw/d. The dose of 60 mg/kg bw/d is considered the NOAEL dose of subchronic toxicity. The NOAEL of maternal and developmental toxicity is 140 mg/kg bw/d. Irritation / sensitisation Undiluted HC Blue n° 12 did not cause any signs of skin irritation in the rabbit. Under the conditions of the test, undiluted HC Blue n° 12 caused transient eye irritation in rabbits. In local lymph node assay, the test substance was considered to be a moderate skin sensitising agent. Dermal absorption","endpoint":"repeated dose toxicity","ingredient":"HC Blue No. 12","loael_value":"","noael_unit":"mg/kg bw/d","noael_value":"60","page":29,"route":"dermal","species":"rat","study_id":"sccp_o_149_noael_011"}
UnifiedCodex:SCCS_SHADOW:beta.noael_studies repeated dose toxicity 140 mg/kg bw/d rat dermal 28 day repeated dose toxicity SOURCE_SUBDIR=sccp_o_149; REPORT_TITLE=OPINION ON HC Blue n° 12 COLIPA n° B73; OPINION_NUMBER=SCCP/1209/08; COMMITTEE=Scientific Committee on Consumer Products (SCCP); REPORT_DATE=adopted on 18 December 2007; VALUE_TEXT=140; DOSE=General toxicity In acute toxicity studies in mice and rats, based on the mortality rates LD50 figures from 1668 to 1775 mg/kg bw were calculated.; EFFECT=one to nitrosation. It should not be used in combination with nitrosating substances. The nitrosamine content should be < 50 ppb. No data submitted for the stability of the test substance in solutions or in the marketed products. General toxicity In acute toxicity studies in mice and rats, based on the mortality rates LD50 figures from 1668 to 1775 mg/kg bw were calculated. The NOAEL of the 28 day toxicity study is 316 mg/kg bw/d. The dose of 60 mg/kg bw/d is considered the NOAEL dose of subchronic toxicity. The NOAEL of maternal and developmental toxicity is 140 mg/kg bw/d. Irritation / sensitisation Undiluted HC Blue n° 12 did not cause any signs of skin irritation in the rabbit. Under the conditions of the test, undiluted HC Blue n° 12 caused transient eye irritation in rabbits. In local lymph node assay, the test substance was considered to be a moderate skin sensitising agent. Dermal absorption; CITATION_NUMBERS=[]; DETAILS_JSON={"cas_number":"104576-93-0","citation":"","dose":"General toxicity In acute toxicity studies in mice and rats, based on the mortality rates LD50 figures from 1668 to 1775 mg/kg bw were calculated.","duration":"28 day","effect":"one to nitrosation. It should not be used in combination with nitrosating substances. The nitrosamine content should be < 50 ppb. No data submitted for the stability of the test substance in solutions or in the marketed products. General toxicity In acute toxicity studies in mice and rats, based on the mortality rates LD50 figures from 1668 to 1775 mg/kg bw were calculated. The NOAEL of the 28 day toxicity study is 316 mg/kg bw/d. The dose of 60 mg/kg bw/d is considered the NOAEL dose of subchronic toxicity. The NOAEL of maternal and developmental toxicity is 140 mg/kg bw/d. Irritation / sensitisation Undiluted HC Blue n° 12 did not cause any signs of skin irritation in the rabbit. Under the conditions of the test, undiluted HC Blue n° 12 caused transient eye irritation in rabbits. In local lymph node assay, the test substance was considered to be a moderate skin sensitising agent. Dermal absorption","endpoint":"repeated dose toxicity","ingredient":"HC Blue No. 12","loael_value":"","noael_unit":"mg/kg bw/d","noael_value":"140","page":29,"route":"dermal","species":"rat","study_id":"sccp_o_149_noael_012"}