NOAEL Studies Cosmetic Ingredient

Tetrabromophenol Blue NOAEL Studies

INCI: TETRABROMOPHENOL BLUE

CAS: 4430-25-5

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

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COSMOS DB 3 endpoints
Source Endpoint Type Value Unit Species Route Duration Study Type Reference
COSMOS DB LOAEL 3 mg/kg bw/day rat oral 92 day Subchronic SCCS; van Otterdijk, F. M.; 90-day oral toxicity study with Royal Blue/802175/Tetrabromophenolblue by daily gavage in the rat; NOTOX; 2005
COSMOS DB LOAEL 30 mg/kg bw/day rat oral 6-20 Gestation day Developmental SCCS; Gerspach, R.; Flade, D.; Tetrabromophenol Blue (WR 18042): Prenatal developmentaltoxicity study in the Han Wistar Rat; RCC; 2005
COSMOS DB NOAEL 3 mg/kg bw/day rat oral 6-20 Gestation day Developmental SCCS; Gerspach, R.; Flade, D.; Tetrabromophenol Blue (WR 18042): Prenatal developmentaltoxicity study in the Han Wistar Rat; RCC; 2005
SCCNFP Opinion 20 endpoints
Source Endpoint Type Value Unit Species Route Duration Study Type Reference
SCCNFP Opinion NOAEL =0.2 % - - sub-chronic repeated dose toxicity {"dose":"evaluate possible substance-related changes in absolute and relative body weights (repeated dose study).","effect":"evaluate possible substance-related changes in absolute and relative body weights (repeated dose study). Blue discolouration of the faeces and other body parts was seen in the dose groups 10 and 100 mg/kg bw/day (repeated dose) and in all doses (sub-chronic). No relevant substance-related clinical findings were noted. The NOAEL in the subchronic toxicity study was set at 3 mg/kg bw/day. The NOAEL for maternal toxicity was set at 50 mg/kg bw/day, the NOAEL for teratogenicity was 5 mg/kg bw/day, for embryotoxicity a NOAEL could not be established. Tetrabromophenol Blue is not a skin irritant. Although the neat substance poses a risk of serious damage to the eyes, no effect was noted at the proposed use concentration of 0.2%. Tetrabromophenol Blue is not a sensitiser when used as intended. The percutaneous absorption study is inadequate. Tetrabromophenol has been tested for the induction of gene mutations in bacterial and in mammalian cells. The test item is non mutagenic on bacterial cells. The in vitro mammalian cell test is in","page":16,"pdf":"out283_en.pdf","row_type":"noael_study","study_id":"out283_en_noael_010"}
SCCNFP Opinion NOAEL =0.2 % - - sub-chronic repeated dose toxicity {"dose":"evaluate possible substance-related changes in absolute and relative body weights (repeated dose study).","effect":"evaluate possible substance-related changes in absolute and relative body weights (repeated dose study). Blue discolouration of the faeces and other body parts was seen in the dose groups 10 and 100 mg/kg bw/day (repeated dose) and in all doses (sub-chronic). No relevant substance-related clinical findings were noted. The NOAEL in the subchronic toxicity study was set at 3 mg/kg bw/day. The NOAEL for maternal toxicity was set at 50 mg/kg bw/day, the NOAEL for teratogenicity was 5 mg/kg bw/day, for embryotoxicity a NOAEL could not be established. Tetrabromophenol Blue is not a skin irritant. Although the neat substance poses a risk of serious damage to the eyes, no effect was noted at the proposed use concentration of 0.2%. Tetrabromophenol Blue is not a sensitiser when used as intended. The percutaneous absorption study is inadequate. Tetrabromophenol has been tested for the induction of gene mutations in bacterial and in mammalian cells. The test item is non mutagenic on bacterial cells. The in vitro mammalian cell test is in","page":16,"pdf":"out283_en.pdf","row_type":"noael_study","study_id":"out283_en_noael_010"}
SCCNFP Opinion NOAEL =0.2 % - - sub-chronic repeated dose toxicity {"dose":"evaluate possible substance-related changes in absolute and relative body weights (repeated dose study).","effect":"evaluate possible substance-related changes in absolute and relative body weights (repeated dose study). Blue discolouration of the faeces and other body parts was seen in the dose groups 10 and 100 mg/kg bw/day (repeated dose) and in all doses (sub-chronic). No relevant substance-related clinical findings were noted. The NOAEL in the subchronic toxicity study was set at 3 mg/kg bw/day. The NOAEL for maternal toxicity was set at 50 mg/kg bw/day, the NOAEL for teratogenicity was 5 mg/kg bw/day, for embryotoxicity a NOAEL could not be established. Tetrabromophenol Blue is not a skin irritant. Although the neat substance poses a risk of serious damage to the eyes, no effect was noted at the proposed use concentration of 0.2%. Tetrabromophenol Blue is not a sensitiser when used as intended. The percutaneous absorption study is inadequate. Tetrabromophenol has been tested for the induction of gene mutations in bacterial and in mammalian cells. The test item is non mutagenic on bacterial cells. The in vitro mammalian cell test is in","page":16,"pdf":"out283_en.pdf","row_type":"noael_study","study_id":"out283_en_noael_010"}
SCCNFP Opinion NOAEL =0.2 % - - sub-chronic repeated dose toxicity {"dose":"evaluate possible substance-related changes in absolute and relative body weights (repeated dose study).","effect":"evaluate possible substance-related changes in absolute and relative body weights (repeated dose study). Blue discolouration of the faeces and other body parts was seen in the dose groups 10 and 100 mg/kg bw/day (repeated dose) and in all doses (sub-chronic). No relevant substance-related clinical findings were noted. The NOAEL in the subchronic toxicity study was set at 3 mg/kg bw/day. The NOAEL for maternal toxicity was set at 50 mg/kg bw/day, the NOAEL for teratogenicity was 5 mg/kg bw/day, for embryotoxicity a NOAEL could not be established. Tetrabromophenol Blue is not a skin irritant. Although the neat substance poses a risk of serious damage to the eyes, no effect was noted at the proposed use concentration of 0.2%. Tetrabromophenol Blue is not a sensitiser when used as intended. The percutaneous absorption study is inadequate. Tetrabromophenol has been tested for the induction of gene mutations in bacterial and in mammalian cells. The test item is non mutagenic on bacterial cells. The in vitro mammalian cell test is in","page":16,"pdf":"out283_en.pdf","row_type":"noael_study","study_id":"out283_en_noael_010"}
SCCNFP Opinion NOAEL =3 mg/kg bw/day rat oral Subchronic repeated dose toxicity {"citation":"Ref.: 2b 2","dose":"SCCNFP/0794/04 Evaluation and opinion on Tetrabromophenol Blue _____________________________________________________________________________________________ 8 The authors established a NOAEL of 3 mg/kg bw/day.","effect":"SCCNFP/0794/04 Evaluation and opinion on Tetrabromophenol Blue _____________________________________________________________________________________________ 8 The authors established a NOAEL of 3 mg/kg bw/day. Ref.: 2b 2.3.5 Repeated dose dermal toxicity No data 2.3.6. Repeated dose inhalation toxicity No data 2.3.7. Subchronic oral toxicity Guideline : OECD 408 (1998) Species/strain : SPF-bred Wistar rats Group size : 10 males and 10 females per dose group Test substance : Tetrabromophenol Blue dissolved in water containing 5.3 % polyglycol 600 and 4.2 % of a 50 % aqueous decyl glucoside solution Batch number : TBFB3/02/30 Purity : 96.7-98.8 % Dose levels : 0, 3, 10 and 100 mg","page":8,"pdf":"out283_en.pdf","row_type":"noael_study","study_id":"out283_en_noael_001"}
SCCNFP Opinion NOAEL =3 mg/kg bw/day rat oral Subchronic repeated dose toxicity {"citation":"Ref.: 2b 2","dose":"SCCNFP/0794/04 Evaluation and opinion on Tetrabromophenol Blue _____________________________________________________________________________________________ 8 The authors established a NOAEL of 3 mg/kg bw/day.","effect":"SCCNFP/0794/04 Evaluation and opinion on Tetrabromophenol Blue _____________________________________________________________________________________________ 8 The authors established a NOAEL of 3 mg/kg bw/day. Ref.: 2b 2.3.5 Repeated dose dermal toxicity No data 2.3.6. Repeated dose inhalation toxicity No data 2.3.7. Subchronic oral toxicity Guideline : OECD 408 (1998) Species/strain : SPF-bred Wistar rats Group size : 10 males and 10 females per dose group Test substance : Tetrabromophenol Blue dissolved in water containing 5.3 % polyglycol 600 and 4.2 % of a 50 % aqueous decyl glucoside solution Batch number : TBFB3/02/30 Purity : 96.7-98.8 % Dose levels : 0, 3, 10 and 100 mg","page":8,"pdf":"out283_en.pdf","row_type":"noael_study","study_id":"out283_en_noael_001"}
SCCNFP Opinion NOAEL =3 mg/kg bw/day rat oral Subchronic repeated dose toxicity {"citation":"Ref.: 2b 2","dose":"SCCNFP/0794/04 Evaluation and opinion on Tetrabromophenol Blue _____________________________________________________________________________________________ 8 The authors established a NOAEL of 3 mg/kg bw/day.","effect":"SCCNFP/0794/04 Evaluation and opinion on Tetrabromophenol Blue _____________________________________________________________________________________________ 8 The authors established a NOAEL of 3 mg/kg bw/day. Ref.: 2b 2.3.5 Repeated dose dermal toxicity No data 2.3.6. Repeated dose inhalation toxicity No data 2.3.7. Subchronic oral toxicity Guideline : OECD 408 (1998) Species/strain : SPF-bred Wistar rats Group size : 10 males and 10 females per dose group Test substance : Tetrabromophenol Blue dissolved in water containing 5.3 % polyglycol 600 and 4.2 % of a 50 % aqueous decyl glucoside solution Batch number : TBFB3/02/30 Purity : 96.7-98.8 % Dose levels : 0, 3, 10 and 100 mg","page":8,"pdf":"out283_en.pdf","row_type":"noael_study","study_id":"out283_en_noael_001"}
SCCNFP Opinion NOAEL =3 mg/kg bw/day rat oral Subchronic repeated dose toxicity {"citation":"Ref.: 2b 2","dose":"SCCNFP/0794/04 Evaluation and opinion on Tetrabromophenol Blue _____________________________________________________________________________________________ 8 The authors established a NOAEL of 3 mg/kg bw/day.","effect":"SCCNFP/0794/04 Evaluation and opinion on Tetrabromophenol Blue _____________________________________________________________________________________________ 8 The authors established a NOAEL of 3 mg/kg bw/day. Ref.: 2b 2.3.5 Repeated dose dermal toxicity No data 2.3.6. Repeated dose inhalation toxicity No data 2.3.7. Subchronic oral toxicity Guideline : OECD 408 (1998) Species/strain : SPF-bred Wistar rats Group size : 10 males and 10 females per dose group Test substance : Tetrabromophenol Blue dissolved in water containing 5.3 % polyglycol 600 and 4.2 % of a 50 % aqueous decyl glucoside solution Batch number : TBFB3/02/30 Purity : 96.7-98.8 % Dose levels : 0, 3, 10 and 100 mg","page":8,"pdf":"out283_en.pdf","row_type":"noael_study","study_id":"out283_en_noael_001"}
SCCNFP Opinion NOAEL =5 mg/kg bw/day - - - NOAEL study {"dose":"Incidental cases of malformations were seen in all dose groups including controls (e.g. polydactyly, exencephaly, spina bifida, abnormal shape of limb bones) but the effects were not dose-related.","effect":"bw/day a generalised reduction in ossification was seen. Incidental cases of malformations were seen in all dose groups including controls (e.g. polydactyly, exencephaly, spina bifida, abnormal shape of limb bones) but the effects were not dose-related. In the high dose group 18 of 166 analysed foetuses showed changes of the major arteries which should be attributed to treatment. Even in the medium dose one foetus with persistent truncus arteriosus was found. The NOAEL of maternal toxicity was 50 mg/kg bw/day, the NOAEL of teratogenicity was 5 mg/kg bw/day. For embryotoxicity, a NOAEL cannot be established. Ref.: 7","page":12,"pdf":"out283_en.pdf","row_type":"noael_study","study_id":"out283_en_noael_005"}
SCCNFP Opinion NOAEL =5 mg/kg bw/day - - - NOAEL study {"dose":"Incidental cases of malformations were seen in all dose groups including controls (e.g. polydactyly, exencephaly, spina bifida, abnormal shape of limb bones) but the effects were not dose-related.","effect":"bw/day a generalised reduction in ossification was seen. Incidental cases of malformations were seen in all dose groups including controls (e.g. polydactyly, exencephaly, spina bifida, abnormal shape of limb bones) but the effects were not dose-related. In the high dose group 18 of 166 analysed foetuses showed changes of the major arteries which should be attributed to treatment. Even in the medium dose one foetus with persistent truncus arteriosus was found. The NOAEL of maternal toxicity was 50 mg/kg bw/day, the NOAEL of teratogenicity was 5 mg/kg bw/day. For embryotoxicity, a NOAEL cannot be established. Ref.: 7","page":12,"pdf":"out283_en.pdf","row_type":"noael_study","study_id":"out283_en_noael_005"}
SCCNFP Opinion NOAEL =5 mg/kg bw/day - - - NOAEL study {"dose":"Incidental cases of malformations were seen in all dose groups including controls (e.g. polydactyly, exencephaly, spina bifida, abnormal shape of limb bones) but the effects were not dose-related.","effect":"bw/day a generalised reduction in ossification was seen. Incidental cases of malformations were seen in all dose groups including controls (e.g. polydactyly, exencephaly, spina bifida, abnormal shape of limb bones) but the effects were not dose-related. In the high dose group 18 of 166 analysed foetuses showed changes of the major arteries which should be attributed to treatment. Even in the medium dose one foetus with persistent truncus arteriosus was found. The NOAEL of maternal toxicity was 50 mg/kg bw/day, the NOAEL of teratogenicity was 5 mg/kg bw/day. For embryotoxicity, a NOAEL cannot be established. Ref.: 7","page":12,"pdf":"out283_en.pdf","row_type":"noael_study","study_id":"out283_en_noael_005"}
SCCNFP Opinion NOAEL =5 mg/kg bw/day - - - NOAEL study {"dose":"Incidental cases of malformations were seen in all dose groups including controls (e.g. polydactyly, exencephaly, spina bifida, abnormal shape of limb bones) but the effects were not dose-related.","effect":"bw/day a generalised reduction in ossification was seen. Incidental cases of malformations were seen in all dose groups including controls (e.g. polydactyly, exencephaly, spina bifida, abnormal shape of limb bones) but the effects were not dose-related. In the high dose group 18 of 166 analysed foetuses showed changes of the major arteries which should be attributed to treatment. Even in the medium dose one foetus with persistent truncus arteriosus was found. The NOAEL of maternal toxicity was 50 mg/kg bw/day, the NOAEL of teratogenicity was 5 mg/kg bw/day. For embryotoxicity, a NOAEL cannot be established. Ref.: 7","page":12,"pdf":"out283_en.pdf","row_type":"noael_study","study_id":"out283_en_noael_005"}
SCCNFP Opinion NOAEL =10 mg/kg bw/day - dermal Sub-chronic repeated dose toxicity {"citation":"Ref.: 2 2","dose":"SCCNFP/0794/04 Evaluation and opinion on Tetrabromophenol Blue _____________________________________________________________________________________________ 9 NOAEL of 10 mg/kg bw/day.","effect":"SCCNFP/0794/04 Evaluation and opinion on Tetrabromophenol Blue _____________________________________________________________________________________________ 9 NOAEL of 10 mg/kg bw/day. Due to the ophthalmological and haematological findings at this dose level, the SCCNFP set the NOAEL to 3 mg/kg bw/day. Comment According to Ref. 5 a 2 % solution of Tetrabromophenol Blue has not be classified as eye irritating. For the highest dose in this study 100 mg per kg bw was administered in 5 ml volume per kg. This may be approximately a 2 % solution. Ref.: 2 2.3.8. Sub-chronic dermal toxicity No data 2.3.9. Sub-chronic inhalation toxicity No data 2.3.10. Chronic toxicity No dat","page":9,"pdf":"out283_en.pdf","row_type":"noael_study","study_id":"out283_en_noael_002"}
SCCNFP Opinion NOAEL =10 mg/kg bw/day - dermal Sub-chronic repeated dose toxicity {"citation":"Ref.: 2 2","dose":"SCCNFP/0794/04 Evaluation and opinion on Tetrabromophenol Blue _____________________________________________________________________________________________ 9 NOAEL of 10 mg/kg bw/day.","effect":"SCCNFP/0794/04 Evaluation and opinion on Tetrabromophenol Blue _____________________________________________________________________________________________ 9 NOAEL of 10 mg/kg bw/day. Due to the ophthalmological and haematological findings at this dose level, the SCCNFP set the NOAEL to 3 mg/kg bw/day. Comment According to Ref. 5 a 2 % solution of Tetrabromophenol Blue has not be classified as eye irritating. For the highest dose in this study 100 mg per kg bw was administered in 5 ml volume per kg. This may be approximately a 2 % solution. Ref.: 2 2.3.8. Sub-chronic dermal toxicity No data 2.3.9. Sub-chronic inhalation toxicity No data 2.3.10. Chronic toxicity No dat","page":9,"pdf":"out283_en.pdf","row_type":"noael_study","study_id":"out283_en_noael_002"}
SCCNFP Opinion NOAEL =10 mg/kg bw/day - dermal Sub-chronic repeated dose toxicity {"citation":"Ref.: 2 2","dose":"SCCNFP/0794/04 Evaluation and opinion on Tetrabromophenol Blue _____________________________________________________________________________________________ 9 NOAEL of 10 mg/kg bw/day.","effect":"SCCNFP/0794/04 Evaluation and opinion on Tetrabromophenol Blue _____________________________________________________________________________________________ 9 NOAEL of 10 mg/kg bw/day. Due to the ophthalmological and haematological findings at this dose level, the SCCNFP set the NOAEL to 3 mg/kg bw/day. Comment According to Ref. 5 a 2 % solution of Tetrabromophenol Blue has not be classified as eye irritating. For the highest dose in this study 100 mg per kg bw was administered in 5 ml volume per kg. This may be approximately a 2 % solution. Ref.: 2 2.3.8. Sub-chronic dermal toxicity No data 2.3.9. Sub-chronic inhalation toxicity No data 2.3.10. Chronic toxicity No dat","page":9,"pdf":"out283_en.pdf","row_type":"noael_study","study_id":"out283_en_noael_002"}
SCCNFP Opinion NOAEL =10 mg/kg bw/day - dermal Sub-chronic repeated dose toxicity {"citation":"Ref.: 2 2","dose":"SCCNFP/0794/04 Evaluation and opinion on Tetrabromophenol Blue _____________________________________________________________________________________________ 9 NOAEL of 10 mg/kg bw/day.","effect":"SCCNFP/0794/04 Evaluation and opinion on Tetrabromophenol Blue _____________________________________________________________________________________________ 9 NOAEL of 10 mg/kg bw/day. Due to the ophthalmological and haematological findings at this dose level, the SCCNFP set the NOAEL to 3 mg/kg bw/day. Comment According to Ref. 5 a 2 % solution of Tetrabromophenol Blue has not be classified as eye irritating. For the highest dose in this study 100 mg per kg bw was administered in 5 ml volume per kg. This may be approximately a 2 % solution. Ref.: 2 2.3.8. Sub-chronic dermal toxicity No data 2.3.9. Sub-chronic inhalation toxicity No data 2.3.10. Chronic toxicity No dat","page":9,"pdf":"out283_en.pdf","row_type":"noael_study","study_id":"out283_en_noael_002"}
SCCNFP Opinion NOAEL =50 mg/kg bw/day - - - NOAEL study {"dose":"half of the 50 mg/kg dose.","effect":"half of the 50 mg/kg dose. At the low dose 5 mg/kg bw/day a generalised reduction in ossification was seen. Incidental cases of malformations were seen in all dose groups including controls (e.g. polydactyly, exencephaly, spina bifida, abnormal shape of limb bones) but the effects were not dose-related. In the high dose group 18 of 166 analysed foetuses showed changes of the major arteries which should be attributed to treatment. Even in the medium dose one foetus with persistent truncus arteriosus was found. The NOAEL of maternal toxicity was 50 mg/kg bw/day, the NOAEL of teratogenicity was 5 mg/kg bw/day. For embryotoxicity, a NOAEL cannot be established. Ref.: 7","page":12,"pdf":"out283_en.pdf","row_type":"noael_study","study_id":"out283_en_noael_004"}
SCCNFP Opinion NOAEL =50 mg/kg bw/day - - - NOAEL study {"dose":"half of the 50 mg/kg dose.","effect":"half of the 50 mg/kg dose. At the low dose 5 mg/kg bw/day a generalised reduction in ossification was seen. Incidental cases of malformations were seen in all dose groups including controls (e.g. polydactyly, exencephaly, spina bifida, abnormal shape of limb bones) but the effects were not dose-related. In the high dose group 18 of 166 analysed foetuses showed changes of the major arteries which should be attributed to treatment. Even in the medium dose one foetus with persistent truncus arteriosus was found. The NOAEL of maternal toxicity was 50 mg/kg bw/day, the NOAEL of teratogenicity was 5 mg/kg bw/day. For embryotoxicity, a NOAEL cannot be established. Ref.: 7","page":12,"pdf":"out283_en.pdf","row_type":"noael_study","study_id":"out283_en_noael_004"}
SCCNFP Opinion NOAEL =50 mg/kg bw/day - - - NOAEL study {"dose":"half of the 50 mg/kg dose.","effect":"half of the 50 mg/kg dose. At the low dose 5 mg/kg bw/day a generalised reduction in ossification was seen. Incidental cases of malformations were seen in all dose groups including controls (e.g. polydactyly, exencephaly, spina bifida, abnormal shape of limb bones) but the effects were not dose-related. In the high dose group 18 of 166 analysed foetuses showed changes of the major arteries which should be attributed to treatment. Even in the medium dose one foetus with persistent truncus arteriosus was found. The NOAEL of maternal toxicity was 50 mg/kg bw/day, the NOAEL of teratogenicity was 5 mg/kg bw/day. For embryotoxicity, a NOAEL cannot be established. Ref.: 7","page":12,"pdf":"out283_en.pdf","row_type":"noael_study","study_id":"out283_en_noael_004"}
SCCNFP Opinion NOAEL =50 mg/kg bw/day - - - NOAEL study {"dose":"half of the 50 mg/kg dose.","effect":"half of the 50 mg/kg dose. At the low dose 5 mg/kg bw/day a generalised reduction in ossification was seen. Incidental cases of malformations were seen in all dose groups including controls (e.g. polydactyly, exencephaly, spina bifida, abnormal shape of limb bones) but the effects were not dose-related. In the high dose group 18 of 166 analysed foetuses showed changes of the major arteries which should be attributed to treatment. Even in the medium dose one foetus with persistent truncus arteriosus was found. The NOAEL of maternal toxicity was 50 mg/kg bw/day, the NOAEL of teratogenicity was 5 mg/kg bw/day. For embryotoxicity, a NOAEL cannot be established. Ref.: 7","page":12,"pdf":"out283_en.pdf","row_type":"noael_study","study_id":"out283_en_noael_004"}
SCCS Opinion 84 endpoints
Source Endpoint Type Value Unit Species Route Duration Study Type Reference
SCCS Opinion NOAEL =3 mg/kg bw/day rat oral Sub-chronic repeated dose toxicity {"citation":"Ref.: 2b, subm I 3","dose":"High dose animals showed an increase in white blood cell counts (males) and increases in cholesterol and glucose (females) while at 10 mg/kg bw/day only one male showed a high glucose value.","effect":"treatment-related effects. High dose animals showed an increase in white blood cell counts (males) and increases in cholesterol and glucose (females) while at 10 mg/kg bw/day only one male showed a high glucose value. Discolouration of the caecum related to the staining properties of the test substance was noted in high dose animals. Missing values in male control organ and body weights make it difficult to evaluate possible substance-related changes in absolute and relative body weights. The authors established a NOAEL of 3 mg/kg bw/day. Ref.: 2b, subm I 3.3.5.2. Sub-chronic (90 days) toxicity (oral, dermal) Taken from SCCNFP/0797/04, re-evaluated Guideline: OECD 408 (1998) Species/strain: SPF-bred Wistar rats Group size: 10 males and 10 females per dose group Test substance: Tetrabromophenol Blue dissolved in water containing 5.3% polyglycol 600 and 4.2% of a 50% aqueous decyl glucoside solution Batch: TBFB3/02/30 Purity: 96.7-98.8% Dose levels: 0, 3, 10 and 100 mg/kg bw/day by oral gavage Route: oral gavage GLP: in complian","page":16,"pdf":"sccs_o_101.pdf","row_type":"noael_study","study_id":"sccs_o_101_noael_001"}
SCCS Opinion NOAEL =10 mg/kg bw/day - - 90-day NOAEL study {"citation":"Ref.: 12 Comment The SCCNFP remarked that according to Ref","dose":"and not considered as toxicologically relevant, but changes in platelet values (males) at 100 mg/kg bw/day and changes in erythrocytes counts observed in males which were statistically significant at 10 and 100 mg/kg bw/day point to a haematotoxic potential of the test substance.","effect":"and not considered as toxicologically relevant, but changes in platelet values (males) at 100 mg/kg bw/day and changes in erythrocytes counts observed in males which were statistically significant at 10 and 100 mg/kg bw/day point to a haematotoxic potential of the test substance. Following the dose of 100 mg/kg bw/day changes in urea (males) and cholesterol (females) values were found. Discolouration of the gastro-intestinal tract was observed and related to the staining properties. The study authors established a NOAEL of 10 mg/kg bw/day. Due to the ophthalmological and haematological findings at this dose level, the SCCNFP set the NOAEL to 3 mg/kg bw/day. Ref.: 12 Comment The SCCNFP remarked that according to Ref. 15 (Ref. 5 subm. I), a 2% solution of Tetrabromophenol Blue has not been classified as eye irritating and no corneal opacity was observed at this concentration. However, for the highest dose in this 90-day study 100 mg per kg bw was administered in 5 ml volume per kg, which corresponds to a 2% solution and the observ","page":17,"pdf":"sccs_o_101.pdf","row_type":"noael_study","study_id":"sccs_o_101_noael_002"}
SCCS Opinion NOAEL =50 mg/kg bw/day rat - - NOAEL study {"citation":"Ref.: 17 New study, submission 2005 Guideline: OECD no","dose":"half of the 50 mg/kg dose.","effect":"half of the 50 mg/kg dose. At the low dose 5 mg/kg bw/day a generalised reduction in ossification was seen. Incidental cases of malformations were seen in all dose groups including controls (e.g. polydactyly, exencephaly, spina bifida, abnormal shape of limb bones) but the effects were not dose-related. In the high dose group 18 of 166 analysed foetuses showed changes of the major arteries which should be attributed to treatment. Even in the medium dose one foetus with persistent truncus arteriosus was found. The NOAEL of maternal toxicity was 50 mg/kg bw/day, the NOAEL of teratogenicity was 5 mg/kg bw/day. For embryotoxicity, a NOAEL cannot be established. Ref.: 17 New study, submission 2005 Guideline: OECD no. 414 (2001) Species/strain: Rat, strain Wistar rats HanBrl: WIST, outbred (SPF) Group size: 22 mated females per dose group Test item: Tetrabromophenol Blue Batch: TBFB3/02/30 Purity: 98.8 area % (at 615 nm, HPLC) Dose levels: 0, 3, 30 and 300 mg/kg bw/day Vehicle: 5% w/w polyglycol 600, 4% w/w Plantaren 2000 UP (50% a","page":21,"pdf":"sccs_o_101.pdf","row_type":"noael_study","study_id":"sccs_o_101_noael_004"}
SCCS Opinion NOAEL =5 mg/kg bw/day rat - - NOAEL study {"citation":"Ref.: 17 New study, submission 2005 Guideline: OECD no","dose":"cases of malformations were seen in all dose groups including controls (e.g. polydactyly, exencephaly, spina bifida, abnormal shape of limb bones) but the effects were not dose-related.","effect":"cases of malformations were seen in all dose groups including controls (e.g. polydactyly, exencephaly, spina bifida, abnormal shape of limb bones) but the effects were not dose-related. In the high dose group 18 of 166 analysed foetuses showed changes of the major arteries which should be attributed to treatment. Even in the medium dose one foetus with persistent truncus arteriosus was found. The NOAEL of maternal toxicity was 50 mg/kg bw/day, the NOAEL of teratogenicity was 5 mg/kg bw/day. For embryotoxicity, a NOAEL cannot be established. Ref.: 17 New study, submission 2005 Guideline: OECD no. 414 (2001) Species/strain: Rat, strain Wistar rats HanBrl: WIST, outbred (SPF) Group size: 22 mated females per dose group Test item: Tetrabromophenol Blue Batch: TBFB3/02/30 Purity: 98.8 area % (at 615 nm, HPLC) Dose levels: 0, 3, 30 and 300 mg/kg bw/day Vehicle: 5% w/w polyglycol 600, 4% w/w Plantaren 2000 UP (50% aqueous","page":21,"pdf":"sccs_o_101.pdf","row_type":"noael_study","study_id":"sccs_o_101_noael_006"}
SCCS Opinion NOAEL =30 mg/kg bw/ day rat - - NOAEL study {"citation":"Ref: 18 3","dose":"d incidences of left-sided umbilical arteries and cranially elongated thymuses at the high dose and anophthalmia in the mid dose group.","effect":"d incidences of left-sided umbilical arteries and cranially elongated thymuses at the high dose and anophthalmia in the mid dose group. There was an increased incidence of fused zygomatic arches at the high dose (21 in 12 litters) when compared with the control group (12 in 9 litters). A statistically significant increase in supernumerary rudimentary ribs was observed in the mid and high doses. No changes were noted in the foetuses of the low dose group (3 mg/kg bw). Conclusion Based on these results the maternal NOAEL was considered to be 30 mg/kg bw/ day. A NOAEL for embryo-foetal effects was derived at 3 mg/kg bw/day. Ref: 18 3.3.9. Toxicokinetics Guideline: OECD 417 (1984) and OECD 427 (2004) Species/strain: Rat, Wistar CRL: WI BR (outbreed) (SPF) Group size: Females, mass balance groups (groups 1,2,3,4) 4 per dose; toxicokinetics groups (groups 5, 6, 7, 8) 6 per dose Test substances: Tetrabromophenol Blue-(Phenol-UL-14C) Batch: 064K9418 non-labelled Tetrabromophenol Blue Batch: TBFB3/02/30 Purity: Radiochemical purity: 88","page":23,"pdf":"sccs_o_101.pdf","row_type":"noael_study","study_id":"sccs_o_101_noael_007"}
SCCS Opinion NOAEL =0.0434 mg/kg bw/d rat oral sub-chronic repeated dose toxicity {"citation":"(Ref. 21)","dose":"Safety evaluation (including calculation of the MoS) CALCULATION OF THE MARGIN OF SAFETY INCI Name Non oxidative conditions Absorption through the skin A = 4.49 µg/cm2 Skin Area surface SAS = 580 cm2 Dermal absorption per treatment SAS x A x 0.001 = 2.60 mg Typical body weight of human = 60 kg Systemic exposure dose SAS x A x 0.001/60 = 0.0434 m...","effect":"SCCS/1426/11 Opinion on Tetrabromophenol Blue ___________________________________________________________________________________________ 26 3.3.13. Safety evaluation (including calculation of the MoS) CALCULATION OF THE MARGIN OF SAFETY INCI Name Non oxidative conditions Absorption through the skin A = 4.49 µg/cm2 Skin Area surface SAS = 580 cm2 Dermal absorption per treatment SAS x A x 0.001 = 2.60 mg Typical body weight of human = 60 kg Systemic exposure dose SAS x A x 0.001/60 = 0.0434 mg/kg bw/d No Observed Adverse Effect Level NOAEL = 3 mg/kg bw/d (rat, oral, teratogenicity and sub-chronic toxicity) Corrected for 30% oral bio-availability (Ref. 21) = 0.9 mg/kg bw/d MOS = 21 3.3.14. Discussion Physico-chemical properties Tetrabromophenol Blue is used in oxidative- as well as in non-oxidative hair dye formulations at a maximum concentration of 0.2% on the scalp. The name Tetrabromophenol Blue of the test material is misleading, since the main component is an octabromo-derivative (42%, quantitative HPLC analysis using standard referen","page":26,"pdf":"sccs_o_101.pdf","row_type":"noael_study","study_id":"sccs_o_101_noael_009"}
SCCS Opinion NOAEL =4 - human - - genotoxicity {"effect":"crease of the major components, homologue (4) and (5) in batch 7215600060 by maximally 2.49 fold versus batch TBFB2/02/30 is covered. This is supported by (a) the absence of in vitro genotoxicity in the Ames Test and the In Vitro Human Lymphocyte Micronucleus Assay (b) the absence of skin and mucous membrane irritation or skin sensitization properties of batch TBFB2/02/30 at concentrations 10 fold above use condition (c) a MoS of 529 and 923 for non-oxidative and oxidative conditions, respectively, when the lowest NOAEL for batch TBFB2/02/30 was adjusted for the increases in the two major components of batch 7215600060","page":12,"pdf":"sccs_o_232.pdf","row_type":"noael_study","study_id":"sccs_o_232_noael_001"}
SCCS Opinion NOAEL =100 mg/kg bw/day - - 90-day NOAEL study {"citation":"Ref.: 1 (Submission I) Ref","dose":"rocytes counts observed in males which were statistically significant at 10 and 100 mg/kg bw/day point to a haematotoxic potential of the test substance.","effect":"rocytes counts observed in males which were statistically significant at 10 and 100 mg/kg bw/day point to a haematotoxic potential of the test substance. Following the dose of 100 mg/kg bw/day changes in urea (males) and cholesterol (females) values were found. Discolouration of the gastro-intestinal tract was observed, related to the staining properties. No treatment-related changes were observed in organ weights or in the histopathological examination of organs and tissues. The study report authors established a NOAEL of 100 mg/kg bw/day. Due to the ophthalmological and haematological findings at this dose level, the SCCNFP set the NOAEL to 3 mg/kg bw/day. Ref.: 1 (Submission I) Ref.: 1 (Submission II) SCCS comment The SCCNFP remarked that according to Ref. 15 (Ref. 5 subm. I), a 2% solution of Tetrabromophenol Blue has not been classified as eye irritating and no corneal opacity was observed at this concentration. However, for the highest dose in this 90-day study, 100 mg per kg bw was administered in 5 ml volume per kg, whi","page":31,"pdf":"sccs_o_232.pdf","row_type":"noael_study","study_id":"sccs_o_232_noael_002"}
SCCS Opinion NOAEL =0.00068 mg/kg bw rat oral 90-day dermal absorption {"citation":"(ref. 21)","dose":"Opinion on hair dye Tetrabromophenol Blue, 4,4’-(4,5,6,7-tetrabromo-1,1-dioxido-3H-2,1-benzoxathiol-3-yliden)bis- 2,6-dibromophenol (C183) – Submission IV _____________________________________________________________________________________________________________________ 46 Absorption through the skin A = 0.07 µg/cm² Skin Surface Area SSA = 580...","effect":"Opinion on hair dye Tetrabromophenol Blue, 4,4’-(4,5,6,7-tetrabromo-1,1-dioxido-3H-2,1-benzoxathiol-3-yliden)bis- 2,6-dibromophenol (C183) – Submission IV _____________________________________________________________________________________________________________________ 46 Absorption through the skin A = 0.07 µg/cm² Skin Surface Area SSA = 580 cm2 Dermal absorption per treatment SSA x A x 0.001 = 0.0406 mg Typical body weight of human = 60 kg Systemic exposure dose (SED) SSA x A x 0.001/60 = 0.00068 mg/kg bw No observed adverse effect level NOAEL = 3 mg/kg bw/d (90-day, oral, rat) Bioavailability 30%* = 0.9 mg/kg bw/d Margin of Safety adjusted NOAEL/SED = 1300 * based on the toxicokinetic study (ref. 21). CALCULATION OF THE MARGIN OF SAFETY (oxidative conditions) (In formulation, on head concentration 0.2%) Absorption through the skin A = 0.04 µg/cm² Skin Surface Area SSA = 580 cm2 Dermal absorption per treatment SSA x A x 0.001 = 0.0232 mg Typical body weight of human = 60 kg Systemic exposure dose (SED) SSA x A x 0.001/60 = 0.00039 mg/kg bw N","page":46,"pdf":"sccs_o_232.pdf","row_type":"noael_study","study_id":"sccs_o_232_noael_014"}
SCCS Opinion NOAEL =3 mg/kg bw/d rat oral 90-day dermal absorption {"citation":"(ref. 21)","dose":"henol Blue, 4,4’-(4,5,6,7-tetrabromo-1,1-dioxido-3H-2,1-benzoxathiol-3-yliden)bis- 2,6-dibromophenol (C183) – Submission IV _____________________________________________________________________________________________________________________ 46 Absorption through the skin A = 0.07 µg/cm² Skin Surface Area SSA = 580 cm2 Dermal absorption per trea...","effect":"henol Blue, 4,4’-(4,5,6,7-tetrabromo-1,1-dioxido-3H-2,1-benzoxathiol-3-yliden)bis- 2,6-dibromophenol (C183) – Submission IV _____________________________________________________________________________________________________________________ 46 Absorption through the skin A = 0.07 µg/cm² Skin Surface Area SSA = 580 cm2 Dermal absorption per treatment SSA x A x 0.001 = 0.0406 mg Typical body weight of human = 60 kg Systemic exposure dose (SED) SSA x A x 0.001/60 = 0.00068 mg/kg bw No observed adverse effect level NOAEL = 3 mg/kg bw/d (90-day, oral, rat) Bioavailability 30%* = 0.9 mg/kg bw/d Margin of Safety adjusted NOAEL/SED = 1300 * based on the toxicokinetic study (ref. 21). CALCULATION OF THE MARGIN OF SAFETY (oxidative conditions) (In formulation, on head concentration 0.2%) Absorption through the skin A = 0.04 µg/cm² Skin Surface Area SSA = 580 cm2 Dermal absorption per treatment SSA x A x 0.001 = 0.0232 mg Typical body weight of human = 60 kg Systemic exposure dose (SED) SSA x A x 0.001/60 = 0.00039 mg/kg bw No obse","page":46,"pdf":"sccs_o_232.pdf","row_type":"noael_study","study_id":"sccs_o_232_noael_015"}
SCCS Opinion NOAEL =0.9 mg/kg bw/d rat oral 90-day dermal absorption {"citation":"(ref. 21)","dose":"3) – Submission IV _____________________________________________________________________________________________________________________ 46 Absorption through the skin A = 0.07 µg/cm² Skin Surface Area SSA = 580 cm2 Dermal absorption per treatment SSA x A x 0.001 = 0.0406 mg Typical body weight of human = 60 kg Systemic exposure dose (SED) SSA x...","effect":"3) – Submission IV _____________________________________________________________________________________________________________________ 46 Absorption through the skin A = 0.07 µg/cm² Skin Surface Area SSA = 580 cm2 Dermal absorption per treatment SSA x A x 0.001 = 0.0406 mg Typical body weight of human = 60 kg Systemic exposure dose (SED) SSA x A x 0.001/60 = 0.00068 mg/kg bw No observed adverse effect level NOAEL = 3 mg/kg bw/d (90-day, oral, rat) Bioavailability 30%* = 0.9 mg/kg bw/d Margin of Safety adjusted NOAEL/SED = 1300 * based on the toxicokinetic study (ref. 21). CALCULATION OF THE MARGIN OF SAFETY (oxidative conditions) (In formulation, on head concentration 0.2%) Absorption through the skin A = 0.04 µg/cm² Skin Surface Area SSA = 580 cm2 Dermal absorption per treatment SSA x A x 0.001 = 0.0232 mg Typical body weight of human = 60 kg Systemic exposure dose (SED) SSA x A x 0.001/60 = 0.00039 mg/kg bw No observed adverse effect level NOAEL = 3 mg/kg bw/d (90-day, oral, rat) Bioavailability 30%* = 0.9 mg/kg bw/d","page":46,"pdf":"sccs_o_232.pdf","row_type":"noael_study","study_id":"sccs_o_232_noael_016"}
SCCS Opinion NOAEL =0.00039 mg/kg bw rat oral 90-day dermal absorption {"citation":"(ref. 21)","dose":"l NOAEL = 3 mg/kg bw/d (90-day, oral, rat) Bioavailability 30%* = 0.9 mg/kg bw/d Margin of Safety adjusted NOAEL/SED = 1300 * based on the toxicokinetic study (ref.","effect":"l NOAEL = 3 mg/kg bw/d (90-day, oral, rat) Bioavailability 30%* = 0.9 mg/kg bw/d Margin of Safety adjusted NOAEL/SED = 1300 * based on the toxicokinetic study (ref. 21). CALCULATION OF THE MARGIN OF SAFETY (oxidative conditions) (In formulation, on head concentration 0.2%) Absorption through the skin A = 0.04 µg/cm² Skin Surface Area SSA = 580 cm2 Dermal absorption per treatment SSA x A x 0.001 = 0.0232 mg Typical body weight of human = 60 kg Systemic exposure dose (SED) SSA x A x 0.001/60 = 0.00039 mg/kg bw No observed adverse effect level NOAEL = 3 mg/kg bw/d (90-day, oral, rat) Bioavailability 30%* = 0.9 mg/kg bw/d Margin of Safety adjusted NOAEL/SED = 2300 * based on the toxicokinetic study (ref. 21). The above MoS calculations only refer to batch TBFB3/02/30 that was used for the toxicity tests, not the current market quality batches. Because of the large margins of safety (1,300 for non-oxidative conditions and 2,300 for non-oxidative conditions) calculated for the batch TBFB3/02/30, the SCCS has considered that around 2.5 fold relative inc","page":46,"pdf":"sccs_o_232.pdf","row_type":"noael_study","study_id":"sccs_o_232_noael_017"}
SCCS Opinion NOAEL =3 mg/kg bw/day rat oral Sub-chronic repeated dose toxicity {"citation":"Ref.: 2b, subm I 3","dose":"High dose animals showed an increase in white blood cell counts (males) and increases in cholesterol and glucose (females) while at 10 mg/kg bw/day only one male showed a high glucose value.","effect":"treatment-related effects. High dose animals showed an increase in white blood cell counts (males) and increases in cholesterol and glucose (females) while at 10 mg/kg bw/day only one male showed a high glucose value. Discolouration of the caecum related to the staining properties of the test substance was noted in high dose animals. Missing values in male control organ and body weights make it difficult to evaluate possible substance-related changes in absolute and relative body weights. The authors established a NOAEL of 3 mg/kg bw/day. Ref.: 2b, subm I 3.3.5.2. Sub-chronic (90 days) toxicity (oral, dermal) Taken from SCCNFP/0797/04, re-evaluated Guideline: OECD 408 (1998) Species/strain: SPF-bred Wistar rats Group size: 10 males and 10 females per dose group Test substance: Tetrabromophenol Blue dissolved in water containing 5.3% polyglycol 600 and 4.2% of a 50% aqueous decyl glucoside solution Batch: TBFB3/02/30 Purity: 96.7-98.8% Dose levels: 0, 3, 10 and 100 mg/kg bw/day by oral gavage Route: oral gavage GLP: in complian","page":16,"pdf":"sccs_o_101.pdf","row_type":"noael_study","study_id":"sccs_o_101_noael_001"}
SCCS Opinion NOAEL =10 mg/kg bw/day - - 90-day NOAEL study {"citation":"Ref.: 12 Comment The SCCNFP remarked that according to Ref","dose":"and not considered as toxicologically relevant, but changes in platelet values (males) at 100 mg/kg bw/day and changes in erythrocytes counts observed in males which were statistically significant at 10 and 100 mg/kg bw/day point to a haematotoxic potential of the test substance.","effect":"and not considered as toxicologically relevant, but changes in platelet values (males) at 100 mg/kg bw/day and changes in erythrocytes counts observed in males which were statistically significant at 10 and 100 mg/kg bw/day point to a haematotoxic potential of the test substance. Following the dose of 100 mg/kg bw/day changes in urea (males) and cholesterol (females) values were found. Discolouration of the gastro-intestinal tract was observed and related to the staining properties. The study authors established a NOAEL of 10 mg/kg bw/day. Due to the ophthalmological and haematological findings at this dose level, the SCCNFP set the NOAEL to 3 mg/kg bw/day. Ref.: 12 Comment The SCCNFP remarked that according to Ref. 15 (Ref. 5 subm. I), a 2% solution of Tetrabromophenol Blue has not been classified as eye irritating and no corneal opacity was observed at this concentration. However, for the highest dose in this 90-day study 100 mg per kg bw was administered in 5 ml volume per kg, which corresponds to a 2% solution and the observ","page":17,"pdf":"sccs_o_101.pdf","row_type":"noael_study","study_id":"sccs_o_101_noael_002"}
SCCS Opinion NOAEL =50 mg/kg bw/day rat - - NOAEL study {"citation":"Ref.: 17 New study, submission 2005 Guideline: OECD no","dose":"half of the 50 mg/kg dose.","effect":"half of the 50 mg/kg dose. At the low dose 5 mg/kg bw/day a generalised reduction in ossification was seen. Incidental cases of malformations were seen in all dose groups including controls (e.g. polydactyly, exencephaly, spina bifida, abnormal shape of limb bones) but the effects were not dose-related. In the high dose group 18 of 166 analysed foetuses showed changes of the major arteries which should be attributed to treatment. Even in the medium dose one foetus with persistent truncus arteriosus was found. The NOAEL of maternal toxicity was 50 mg/kg bw/day, the NOAEL of teratogenicity was 5 mg/kg bw/day. For embryotoxicity, a NOAEL cannot be established. Ref.: 17 New study, submission 2005 Guideline: OECD no. 414 (2001) Species/strain: Rat, strain Wistar rats HanBrl: WIST, outbred (SPF) Group size: 22 mated females per dose group Test item: Tetrabromophenol Blue Batch: TBFB3/02/30 Purity: 98.8 area % (at 615 nm, HPLC) Dose levels: 0, 3, 30 and 300 mg/kg bw/day Vehicle: 5% w/w polyglycol 600, 4% w/w Plantaren 2000 UP (50% a","page":21,"pdf":"sccs_o_101.pdf","row_type":"noael_study","study_id":"sccs_o_101_noael_004"}
SCCS Opinion NOAEL =5 mg/kg bw/day rat - - NOAEL study {"citation":"Ref.: 17 New study, submission 2005 Guideline: OECD no","dose":"cases of malformations were seen in all dose groups including controls (e.g. polydactyly, exencephaly, spina bifida, abnormal shape of limb bones) but the effects were not dose-related.","effect":"cases of malformations were seen in all dose groups including controls (e.g. polydactyly, exencephaly, spina bifida, abnormal shape of limb bones) but the effects were not dose-related. In the high dose group 18 of 166 analysed foetuses showed changes of the major arteries which should be attributed to treatment. Even in the medium dose one foetus with persistent truncus arteriosus was found. The NOAEL of maternal toxicity was 50 mg/kg bw/day, the NOAEL of teratogenicity was 5 mg/kg bw/day. For embryotoxicity, a NOAEL cannot be established. Ref.: 17 New study, submission 2005 Guideline: OECD no. 414 (2001) Species/strain: Rat, strain Wistar rats HanBrl: WIST, outbred (SPF) Group size: 22 mated females per dose group Test item: Tetrabromophenol Blue Batch: TBFB3/02/30 Purity: 98.8 area % (at 615 nm, HPLC) Dose levels: 0, 3, 30 and 300 mg/kg bw/day Vehicle: 5% w/w polyglycol 600, 4% w/w Plantaren 2000 UP (50% aqueous","page":21,"pdf":"sccs_o_101.pdf","row_type":"noael_study","study_id":"sccs_o_101_noael_006"}
SCCS Opinion NOAEL =30 mg/kg bw/ day rat - - NOAEL study {"citation":"Ref: 18 3","dose":"d incidences of left-sided umbilical arteries and cranially elongated thymuses at the high dose and anophthalmia in the mid dose group.","effect":"d incidences of left-sided umbilical arteries and cranially elongated thymuses at the high dose and anophthalmia in the mid dose group. There was an increased incidence of fused zygomatic arches at the high dose (21 in 12 litters) when compared with the control group (12 in 9 litters). A statistically significant increase in supernumerary rudimentary ribs was observed in the mid and high doses. No changes were noted in the foetuses of the low dose group (3 mg/kg bw). Conclusion Based on these results the maternal NOAEL was considered to be 30 mg/kg bw/ day. A NOAEL for embryo-foetal effects was derived at 3 mg/kg bw/day. Ref: 18 3.3.9. Toxicokinetics Guideline: OECD 417 (1984) and OECD 427 (2004) Species/strain: Rat, Wistar CRL: WI BR (outbreed) (SPF) Group size: Females, mass balance groups (groups 1,2,3,4) 4 per dose; toxicokinetics groups (groups 5, 6, 7, 8) 6 per dose Test substances: Tetrabromophenol Blue-(Phenol-UL-14C) Batch: 064K9418 non-labelled Tetrabromophenol Blue Batch: TBFB3/02/30 Purity: Radiochemical purity: 88","page":23,"pdf":"sccs_o_101.pdf","row_type":"noael_study","study_id":"sccs_o_101_noael_007"}
SCCS Opinion NOAEL =0.0434 mg/kg bw/d rat oral sub-chronic repeated dose toxicity {"citation":"(Ref. 21)","dose":"Safety evaluation (including calculation of the MoS) CALCULATION OF THE MARGIN OF SAFETY INCI Name Non oxidative conditions Absorption through the skin A = 4.49 µg/cm2 Skin Area surface SAS = 580 cm2 Dermal absorption per treatment SAS x A x 0.001 = 2.60 mg Typical body weight of human = 60 kg Systemic exposure dose SAS x A x 0.001/60 = 0.0434 m...","effect":"SCCS/1426/11 Opinion on Tetrabromophenol Blue ___________________________________________________________________________________________ 26 3.3.13. Safety evaluation (including calculation of the MoS) CALCULATION OF THE MARGIN OF SAFETY INCI Name Non oxidative conditions Absorption through the skin A = 4.49 µg/cm2 Skin Area surface SAS = 580 cm2 Dermal absorption per treatment SAS x A x 0.001 = 2.60 mg Typical body weight of human = 60 kg Systemic exposure dose SAS x A x 0.001/60 = 0.0434 mg/kg bw/d No Observed Adverse Effect Level NOAEL = 3 mg/kg bw/d (rat, oral, teratogenicity and sub-chronic toxicity) Corrected for 30% oral bio-availability (Ref. 21) = 0.9 mg/kg bw/d MOS = 21 3.3.14. Discussion Physico-chemical properties Tetrabromophenol Blue is used in oxidative- as well as in non-oxidative hair dye formulations at a maximum concentration of 0.2% on the scalp. The name Tetrabromophenol Blue of the test material is misleading, since the main component is an octabromo-derivative (42%, quantitative HPLC analysis using standard referen","page":26,"pdf":"sccs_o_101.pdf","row_type":"noael_study","study_id":"sccs_o_101_noael_009"}
SCCS Opinion NOAEL =3 mg/kg bw/day rat oral Sub-chronic repeated dose toxicity {"citation":"Ref.: 2b, subm I 3","dose":"High dose animals showed an increase in white blood cell counts (males) and increases in cholesterol and glucose (females) while at 10 mg/kg bw/day only one male showed a high glucose value.","effect":"treatment-related effects. High dose animals showed an increase in white blood cell counts (males) and increases in cholesterol and glucose (females) while at 10 mg/kg bw/day only one male showed a high glucose value. Discolouration of the caecum related to the staining properties of the test substance was noted in high dose animals. Missing values in male control organ and body weights make it difficult to evaluate possible substance-related changes in absolute and relative body weights. The authors established a NOAEL of 3 mg/kg bw/day. Ref.: 2b, subm I 3.3.5.2. Sub-chronic (90 days) toxicity (oral, dermal) Taken from SCCNFP/0797/04, re-evaluated Guideline: OECD 408 (1998) Species/strain: SPF-bred Wistar rats Group size: 10 males and 10 females per dose group Test substance: Tetrabromophenol Blue dissolved in water containing 5.3% polyglycol 600 and 4.2% of a 50% aqueous decyl glucoside solution Batch: TBFB3/02/30 Purity: 96.7-98.8% Dose levels: 0, 3, 10 and 100 mg/kg bw/day by oral gavage Route: oral gavage GLP: in complian","page":16,"pdf":"sccs_o_101.pdf","row_type":"noael_study","study_id":"sccs_o_101_noael_001"}
SCCS Opinion NOAEL =10 mg/kg bw/day - - 90-day NOAEL study {"citation":"Ref.: 12 Comment The SCCNFP remarked that according to Ref","dose":"and not considered as toxicologically relevant, but changes in platelet values (males) at 100 mg/kg bw/day and changes in erythrocytes counts observed in males which were statistically significant at 10 and 100 mg/kg bw/day point to a haematotoxic potential of the test substance.","effect":"and not considered as toxicologically relevant, but changes in platelet values (males) at 100 mg/kg bw/day and changes in erythrocytes counts observed in males which were statistically significant at 10 and 100 mg/kg bw/day point to a haematotoxic potential of the test substance. Following the dose of 100 mg/kg bw/day changes in urea (males) and cholesterol (females) values were found. Discolouration of the gastro-intestinal tract was observed and related to the staining properties. The study authors established a NOAEL of 10 mg/kg bw/day. Due to the ophthalmological and haematological findings at this dose level, the SCCNFP set the NOAEL to 3 mg/kg bw/day. Ref.: 12 Comment The SCCNFP remarked that according to Ref. 15 (Ref. 5 subm. I), a 2% solution of Tetrabromophenol Blue has not been classified as eye irritating and no corneal opacity was observed at this concentration. However, for the highest dose in this 90-day study 100 mg per kg bw was administered in 5 ml volume per kg, which corresponds to a 2% solution and the observ","page":17,"pdf":"sccs_o_101.pdf","row_type":"noael_study","study_id":"sccs_o_101_noael_002"}
SCCS Opinion NOAEL =50 mg/kg bw/day rat - - NOAEL study {"citation":"Ref.: 17 New study, submission 2005 Guideline: OECD no","dose":"half of the 50 mg/kg dose.","effect":"half of the 50 mg/kg dose. At the low dose 5 mg/kg bw/day a generalised reduction in ossification was seen. Incidental cases of malformations were seen in all dose groups including controls (e.g. polydactyly, exencephaly, spina bifida, abnormal shape of limb bones) but the effects were not dose-related. In the high dose group 18 of 166 analysed foetuses showed changes of the major arteries which should be attributed to treatment. Even in the medium dose one foetus with persistent truncus arteriosus was found. The NOAEL of maternal toxicity was 50 mg/kg bw/day, the NOAEL of teratogenicity was 5 mg/kg bw/day. For embryotoxicity, a NOAEL cannot be established. Ref.: 17 New study, submission 2005 Guideline: OECD no. 414 (2001) Species/strain: Rat, strain Wistar rats HanBrl: WIST, outbred (SPF) Group size: 22 mated females per dose group Test item: Tetrabromophenol Blue Batch: TBFB3/02/30 Purity: 98.8 area % (at 615 nm, HPLC) Dose levels: 0, 3, 30 and 300 mg/kg bw/day Vehicle: 5% w/w polyglycol 600, 4% w/w Plantaren 2000 UP (50% a","page":21,"pdf":"sccs_o_101.pdf","row_type":"noael_study","study_id":"sccs_o_101_noael_004"}
SCCS Opinion NOAEL =5 mg/kg bw/day rat - - NOAEL study {"citation":"Ref.: 17 New study, submission 2005 Guideline: OECD no","dose":"cases of malformations were seen in all dose groups including controls (e.g. polydactyly, exencephaly, spina bifida, abnormal shape of limb bones) but the effects were not dose-related.","effect":"cases of malformations were seen in all dose groups including controls (e.g. polydactyly, exencephaly, spina bifida, abnormal shape of limb bones) but the effects were not dose-related. In the high dose group 18 of 166 analysed foetuses showed changes of the major arteries which should be attributed to treatment. Even in the medium dose one foetus with persistent truncus arteriosus was found. The NOAEL of maternal toxicity was 50 mg/kg bw/day, the NOAEL of teratogenicity was 5 mg/kg bw/day. For embryotoxicity, a NOAEL cannot be established. Ref.: 17 New study, submission 2005 Guideline: OECD no. 414 (2001) Species/strain: Rat, strain Wistar rats HanBrl: WIST, outbred (SPF) Group size: 22 mated females per dose group Test item: Tetrabromophenol Blue Batch: TBFB3/02/30 Purity: 98.8 area % (at 615 nm, HPLC) Dose levels: 0, 3, 30 and 300 mg/kg bw/day Vehicle: 5% w/w polyglycol 600, 4% w/w Plantaren 2000 UP (50% aqueous","page":21,"pdf":"sccs_o_101.pdf","row_type":"noael_study","study_id":"sccs_o_101_noael_006"}
SCCS Opinion NOAEL =30 mg/kg bw/ day rat - - NOAEL study {"citation":"Ref: 18 3","dose":"d incidences of left-sided umbilical arteries and cranially elongated thymuses at the high dose and anophthalmia in the mid dose group.","effect":"d incidences of left-sided umbilical arteries and cranially elongated thymuses at the high dose and anophthalmia in the mid dose group. There was an increased incidence of fused zygomatic arches at the high dose (21 in 12 litters) when compared with the control group (12 in 9 litters). A statistically significant increase in supernumerary rudimentary ribs was observed in the mid and high doses. No changes were noted in the foetuses of the low dose group (3 mg/kg bw). Conclusion Based on these results the maternal NOAEL was considered to be 30 mg/kg bw/ day. A NOAEL for embryo-foetal effects was derived at 3 mg/kg bw/day. Ref: 18 3.3.9. Toxicokinetics Guideline: OECD 417 (1984) and OECD 427 (2004) Species/strain: Rat, Wistar CRL: WI BR (outbreed) (SPF) Group size: Females, mass balance groups (groups 1,2,3,4) 4 per dose; toxicokinetics groups (groups 5, 6, 7, 8) 6 per dose Test substances: Tetrabromophenol Blue-(Phenol-UL-14C) Batch: 064K9418 non-labelled Tetrabromophenol Blue Batch: TBFB3/02/30 Purity: Radiochemical purity: 88","page":23,"pdf":"sccs_o_101.pdf","row_type":"noael_study","study_id":"sccs_o_101_noael_007"}
SCCS Opinion NOAEL =0.0434 mg/kg bw/d rat oral sub-chronic repeated dose toxicity {"citation":"(Ref. 21)","dose":"Safety evaluation (including calculation of the MoS) CALCULATION OF THE MARGIN OF SAFETY INCI Name Non oxidative conditions Absorption through the skin A = 4.49 µg/cm2 Skin Area surface SAS = 580 cm2 Dermal absorption per treatment SAS x A x 0.001 = 2.60 mg Typical body weight of human = 60 kg Systemic exposure dose SAS x A x 0.001/60 = 0.0434 m...","effect":"SCCS/1426/11 Opinion on Tetrabromophenol Blue ___________________________________________________________________________________________ 26 3.3.13. Safety evaluation (including calculation of the MoS) CALCULATION OF THE MARGIN OF SAFETY INCI Name Non oxidative conditions Absorption through the skin A = 4.49 µg/cm2 Skin Area surface SAS = 580 cm2 Dermal absorption per treatment SAS x A x 0.001 = 2.60 mg Typical body weight of human = 60 kg Systemic exposure dose SAS x A x 0.001/60 = 0.0434 mg/kg bw/d No Observed Adverse Effect Level NOAEL = 3 mg/kg bw/d (rat, oral, teratogenicity and sub-chronic toxicity) Corrected for 30% oral bio-availability (Ref. 21) = 0.9 mg/kg bw/d MOS = 21 3.3.14. Discussion Physico-chemical properties Tetrabromophenol Blue is used in oxidative- as well as in non-oxidative hair dye formulations at a maximum concentration of 0.2% on the scalp. The name Tetrabromophenol Blue of the test material is misleading, since the main component is an octabromo-derivative (42%, quantitative HPLC analysis using standard referen","page":26,"pdf":"sccs_o_101.pdf","row_type":"noael_study","study_id":"sccs_o_101_noael_009"}
SCCS Opinion NOAEL =4 - human - - genotoxicity {"effect":"crease of the major components, homologue (4) and (5) in batch 7215600060 by maximally 2.49 fold versus batch TBFB2/02/30 is covered. This is supported by (a) the absence of in vitro genotoxicity in the Ames Test and the In Vitro Human Lymphocyte Micronucleus Assay (b) the absence of skin and mucous membrane irritation or skin sensitization properties of batch TBFB2/02/30 at concentrations 10 fold above use condition (c) a MoS of 529 and 923 for non-oxidative and oxidative conditions, respectively, when the lowest NOAEL for batch TBFB2/02/30 was adjusted for the increases in the two major components of batch 7215600060","page":12,"pdf":"sccs_o_232.pdf","row_type":"noael_study","study_id":"sccs_o_232_noael_001"}
SCCS Opinion NOAEL =100 mg/kg bw/day - - 90-day NOAEL study {"citation":"Ref.: 1 (Submission I) Ref","dose":"rocytes counts observed in males which were statistically significant at 10 and 100 mg/kg bw/day point to a haematotoxic potential of the test substance.","effect":"rocytes counts observed in males which were statistically significant at 10 and 100 mg/kg bw/day point to a haematotoxic potential of the test substance. Following the dose of 100 mg/kg bw/day changes in urea (males) and cholesterol (females) values were found. Discolouration of the gastro-intestinal tract was observed, related to the staining properties. No treatment-related changes were observed in organ weights or in the histopathological examination of organs and tissues. The study report authors established a NOAEL of 100 mg/kg bw/day. Due to the ophthalmological and haematological findings at this dose level, the SCCNFP set the NOAEL to 3 mg/kg bw/day. Ref.: 1 (Submission I) Ref.: 1 (Submission II) SCCS comment The SCCNFP remarked that according to Ref. 15 (Ref. 5 subm. I), a 2% solution of Tetrabromophenol Blue has not been classified as eye irritating and no corneal opacity was observed at this concentration. However, for the highest dose in this 90-day study, 100 mg per kg bw was administered in 5 ml volume per kg, whi","page":31,"pdf":"sccs_o_232.pdf","row_type":"noael_study","study_id":"sccs_o_232_noael_002"}
SCCS Opinion NOAEL =0.00068 mg/kg bw rat oral 90-day dermal absorption {"citation":"(ref. 21)","dose":"Opinion on hair dye Tetrabromophenol Blue, 4,4’-(4,5,6,7-tetrabromo-1,1-dioxido-3H-2,1-benzoxathiol-3-yliden)bis- 2,6-dibromophenol (C183) – Submission IV _____________________________________________________________________________________________________________________ 46 Absorption through the skin A = 0.07 µg/cm² Skin Surface Area SSA = 580...","effect":"Opinion on hair dye Tetrabromophenol Blue, 4,4’-(4,5,6,7-tetrabromo-1,1-dioxido-3H-2,1-benzoxathiol-3-yliden)bis- 2,6-dibromophenol (C183) – Submission IV _____________________________________________________________________________________________________________________ 46 Absorption through the skin A = 0.07 µg/cm² Skin Surface Area SSA = 580 cm2 Dermal absorption per treatment SSA x A x 0.001 = 0.0406 mg Typical body weight of human = 60 kg Systemic exposure dose (SED) SSA x A x 0.001/60 = 0.00068 mg/kg bw No observed adverse effect level NOAEL = 3 mg/kg bw/d (90-day, oral, rat) Bioavailability 30%* = 0.9 mg/kg bw/d Margin of Safety adjusted NOAEL/SED = 1300 * based on the toxicokinetic study (ref. 21). CALCULATION OF THE MARGIN OF SAFETY (oxidative conditions) (In formulation, on head concentration 0.2%) Absorption through the skin A = 0.04 µg/cm² Skin Surface Area SSA = 580 cm2 Dermal absorption per treatment SSA x A x 0.001 = 0.0232 mg Typical body weight of human = 60 kg Systemic exposure dose (SED) SSA x A x 0.001/60 = 0.00039 mg/kg bw N","page":46,"pdf":"sccs_o_232.pdf","row_type":"noael_study","study_id":"sccs_o_232_noael_014"}
SCCS Opinion NOAEL =3 mg/kg bw/d rat oral 90-day dermal absorption {"citation":"(ref. 21)","dose":"henol Blue, 4,4’-(4,5,6,7-tetrabromo-1,1-dioxido-3H-2,1-benzoxathiol-3-yliden)bis- 2,6-dibromophenol (C183) – Submission IV _____________________________________________________________________________________________________________________ 46 Absorption through the skin A = 0.07 µg/cm² Skin Surface Area SSA = 580 cm2 Dermal absorption per trea...","effect":"henol Blue, 4,4’-(4,5,6,7-tetrabromo-1,1-dioxido-3H-2,1-benzoxathiol-3-yliden)bis- 2,6-dibromophenol (C183) – Submission IV _____________________________________________________________________________________________________________________ 46 Absorption through the skin A = 0.07 µg/cm² Skin Surface Area SSA = 580 cm2 Dermal absorption per treatment SSA x A x 0.001 = 0.0406 mg Typical body weight of human = 60 kg Systemic exposure dose (SED) SSA x A x 0.001/60 = 0.00068 mg/kg bw No observed adverse effect level NOAEL = 3 mg/kg bw/d (90-day, oral, rat) Bioavailability 30%* = 0.9 mg/kg bw/d Margin of Safety adjusted NOAEL/SED = 1300 * based on the toxicokinetic study (ref. 21). CALCULATION OF THE MARGIN OF SAFETY (oxidative conditions) (In formulation, on head concentration 0.2%) Absorption through the skin A = 0.04 µg/cm² Skin Surface Area SSA = 580 cm2 Dermal absorption per treatment SSA x A x 0.001 = 0.0232 mg Typical body weight of human = 60 kg Systemic exposure dose (SED) SSA x A x 0.001/60 = 0.00039 mg/kg bw No obse","page":46,"pdf":"sccs_o_232.pdf","row_type":"noael_study","study_id":"sccs_o_232_noael_015"}
SCCS Opinion NOAEL =4 - human - - genotoxicity {"effect":"crease of the major components, homologue (4) and (5) in batch 7215600060 by maximally 2.49 fold versus batch TBFB2/02/30 is covered. This is supported by (a) the absence of in vitro genotoxicity in the Ames Test and the In Vitro Human Lymphocyte Micronucleus Assay (b) the absence of skin and mucous membrane irritation or skin sensitization properties of batch TBFB2/02/30 at concentrations 10 fold above use condition (c) a MoS of 529 and 923 for non-oxidative and oxidative conditions, respectively, when the lowest NOAEL for batch TBFB2/02/30 was adjusted for the increases in the two major components of batch 7215600060","page":12,"pdf":"sccs_o_232.pdf","row_type":"noael_study","study_id":"sccs_o_232_noael_001"}
SCCS Opinion NOAEL =100 mg/kg bw/day - - 90-day NOAEL study {"citation":"Ref.: 1 (Submission I) Ref","dose":"rocytes counts observed in males which were statistically significant at 10 and 100 mg/kg bw/day point to a haematotoxic potential of the test substance.","effect":"rocytes counts observed in males which were statistically significant at 10 and 100 mg/kg bw/day point to a haematotoxic potential of the test substance. Following the dose of 100 mg/kg bw/day changes in urea (males) and cholesterol (females) values were found. Discolouration of the gastro-intestinal tract was observed, related to the staining properties. No treatment-related changes were observed in organ weights or in the histopathological examination of organs and tissues. The study report authors established a NOAEL of 100 mg/kg bw/day. Due to the ophthalmological and haematological findings at this dose level, the SCCNFP set the NOAEL to 3 mg/kg bw/day. Ref.: 1 (Submission I) Ref.: 1 (Submission II) SCCS comment The SCCNFP remarked that according to Ref. 15 (Ref. 5 subm. I), a 2% solution of Tetrabromophenol Blue has not been classified as eye irritating and no corneal opacity was observed at this concentration. However, for the highest dose in this 90-day study, 100 mg per kg bw was administered in 5 ml volume per kg, whi","page":31,"pdf":"sccs_o_232.pdf","row_type":"noael_study","study_id":"sccs_o_232_noael_002"}
SCCS Opinion NOAEL =0.00068 mg/kg bw rat oral 90-day dermal absorption {"citation":"(ref. 21)","dose":"Opinion on hair dye Tetrabromophenol Blue, 4,4’-(4,5,6,7-tetrabromo-1,1-dioxido-3H-2,1-benzoxathiol-3-yliden)bis- 2,6-dibromophenol (C183) – Submission IV _____________________________________________________________________________________________________________________ 46 Absorption through the skin A = 0.07 µg/cm² Skin Surface Area SSA = 580...","effect":"Opinion on hair dye Tetrabromophenol Blue, 4,4’-(4,5,6,7-tetrabromo-1,1-dioxido-3H-2,1-benzoxathiol-3-yliden)bis- 2,6-dibromophenol (C183) – Submission IV _____________________________________________________________________________________________________________________ 46 Absorption through the skin A = 0.07 µg/cm² Skin Surface Area SSA = 580 cm2 Dermal absorption per treatment SSA x A x 0.001 = 0.0406 mg Typical body weight of human = 60 kg Systemic exposure dose (SED) SSA x A x 0.001/60 = 0.00068 mg/kg bw No observed adverse effect level NOAEL = 3 mg/kg bw/d (90-day, oral, rat) Bioavailability 30%* = 0.9 mg/kg bw/d Margin of Safety adjusted NOAEL/SED = 1300 * based on the toxicokinetic study (ref. 21). CALCULATION OF THE MARGIN OF SAFETY (oxidative conditions) (In formulation, on head concentration 0.2%) Absorption through the skin A = 0.04 µg/cm² Skin Surface Area SSA = 580 cm2 Dermal absorption per treatment SSA x A x 0.001 = 0.0232 mg Typical body weight of human = 60 kg Systemic exposure dose (SED) SSA x A x 0.001/60 = 0.00039 mg/kg bw N","page":46,"pdf":"sccs_o_232.pdf","row_type":"noael_study","study_id":"sccs_o_232_noael_014"}
SCCS Opinion NOAEL =3 mg/kg bw/d rat oral 90-day dermal absorption {"citation":"(ref. 21)","dose":"henol Blue, 4,4’-(4,5,6,7-tetrabromo-1,1-dioxido-3H-2,1-benzoxathiol-3-yliden)bis- 2,6-dibromophenol (C183) – Submission IV _____________________________________________________________________________________________________________________ 46 Absorption through the skin A = 0.07 µg/cm² Skin Surface Area SSA = 580 cm2 Dermal absorption per trea...","effect":"henol Blue, 4,4’-(4,5,6,7-tetrabromo-1,1-dioxido-3H-2,1-benzoxathiol-3-yliden)bis- 2,6-dibromophenol (C183) – Submission IV _____________________________________________________________________________________________________________________ 46 Absorption through the skin A = 0.07 µg/cm² Skin Surface Area SSA = 580 cm2 Dermal absorption per treatment SSA x A x 0.001 = 0.0406 mg Typical body weight of human = 60 kg Systemic exposure dose (SED) SSA x A x 0.001/60 = 0.00068 mg/kg bw No observed adverse effect level NOAEL = 3 mg/kg bw/d (90-day, oral, rat) Bioavailability 30%* = 0.9 mg/kg bw/d Margin of Safety adjusted NOAEL/SED = 1300 * based on the toxicokinetic study (ref. 21). CALCULATION OF THE MARGIN OF SAFETY (oxidative conditions) (In formulation, on head concentration 0.2%) Absorption through the skin A = 0.04 µg/cm² Skin Surface Area SSA = 580 cm2 Dermal absorption per treatment SSA x A x 0.001 = 0.0232 mg Typical body weight of human = 60 kg Systemic exposure dose (SED) SSA x A x 0.001/60 = 0.00039 mg/kg bw No obse","page":46,"pdf":"sccs_o_232.pdf","row_type":"noael_study","study_id":"sccs_o_232_noael_015"}
SCCS Opinion NOAEL =0.9 mg/kg bw/d rat oral 90-day dermal absorption {"citation":"(ref. 21)","dose":"3) – Submission IV _____________________________________________________________________________________________________________________ 46 Absorption through the skin A = 0.07 µg/cm² Skin Surface Area SSA = 580 cm2 Dermal absorption per treatment SSA x A x 0.001 = 0.0406 mg Typical body weight of human = 60 kg Systemic exposure dose (SED) SSA x...","effect":"3) – Submission IV _____________________________________________________________________________________________________________________ 46 Absorption through the skin A = 0.07 µg/cm² Skin Surface Area SSA = 580 cm2 Dermal absorption per treatment SSA x A x 0.001 = 0.0406 mg Typical body weight of human = 60 kg Systemic exposure dose (SED) SSA x A x 0.001/60 = 0.00068 mg/kg bw No observed adverse effect level NOAEL = 3 mg/kg bw/d (90-day, oral, rat) Bioavailability 30%* = 0.9 mg/kg bw/d Margin of Safety adjusted NOAEL/SED = 1300 * based on the toxicokinetic study (ref. 21). CALCULATION OF THE MARGIN OF SAFETY (oxidative conditions) (In formulation, on head concentration 0.2%) Absorption through the skin A = 0.04 µg/cm² Skin Surface Area SSA = 580 cm2 Dermal absorption per treatment SSA x A x 0.001 = 0.0232 mg Typical body weight of human = 60 kg Systemic exposure dose (SED) SSA x A x 0.001/60 = 0.00039 mg/kg bw No observed adverse effect level NOAEL = 3 mg/kg bw/d (90-day, oral, rat) Bioavailability 30%* = 0.9 mg/kg bw/d","page":46,"pdf":"sccs_o_232.pdf","row_type":"noael_study","study_id":"sccs_o_232_noael_016"}
SCCS Opinion NOAEL =0.00039 mg/kg bw rat oral 90-day dermal absorption {"citation":"(ref. 21)","dose":"l NOAEL = 3 mg/kg bw/d (90-day, oral, rat) Bioavailability 30%* = 0.9 mg/kg bw/d Margin of Safety adjusted NOAEL/SED = 1300 * based on the toxicokinetic study (ref.","effect":"l NOAEL = 3 mg/kg bw/d (90-day, oral, rat) Bioavailability 30%* = 0.9 mg/kg bw/d Margin of Safety adjusted NOAEL/SED = 1300 * based on the toxicokinetic study (ref. 21). CALCULATION OF THE MARGIN OF SAFETY (oxidative conditions) (In formulation, on head concentration 0.2%) Absorption through the skin A = 0.04 µg/cm² Skin Surface Area SSA = 580 cm2 Dermal absorption per treatment SSA x A x 0.001 = 0.0232 mg Typical body weight of human = 60 kg Systemic exposure dose (SED) SSA x A x 0.001/60 = 0.00039 mg/kg bw No observed adverse effect level NOAEL = 3 mg/kg bw/d (90-day, oral, rat) Bioavailability 30%* = 0.9 mg/kg bw/d Margin of Safety adjusted NOAEL/SED = 2300 * based on the toxicokinetic study (ref. 21). The above MoS calculations only refer to batch TBFB3/02/30 that was used for the toxicity tests, not the current market quality batches. Because of the large margins of safety (1,300 for non-oxidative conditions and 2,300 for non-oxidative conditions) calculated for the batch TBFB3/02/30, the SCCS has considered that around 2.5 fold relative inc","page":46,"pdf":"sccs_o_232.pdf","row_type":"noael_study","study_id":"sccs_o_232_noael_017"}
SCCS Opinion NOAEL =0.9 mg/kg bw/d rat oral 90-day dermal absorption {"citation":"(ref. 21)","dose":"3) – Submission IV _____________________________________________________________________________________________________________________ 46 Absorption through the skin A = 0.07 µg/cm² Skin Surface Area SSA = 580 cm2 Dermal absorption per treatment SSA x A x 0.001 = 0.0406 mg Typical body weight of human = 60 kg Systemic exposure dose (SED) SSA x...","effect":"3) – Submission IV _____________________________________________________________________________________________________________________ 46 Absorption through the skin A = 0.07 µg/cm² Skin Surface Area SSA = 580 cm2 Dermal absorption per treatment SSA x A x 0.001 = 0.0406 mg Typical body weight of human = 60 kg Systemic exposure dose (SED) SSA x A x 0.001/60 = 0.00068 mg/kg bw No observed adverse effect level NOAEL = 3 mg/kg bw/d (90-day, oral, rat) Bioavailability 30%* = 0.9 mg/kg bw/d Margin of Safety adjusted NOAEL/SED = 1300 * based on the toxicokinetic study (ref. 21). CALCULATION OF THE MARGIN OF SAFETY (oxidative conditions) (In formulation, on head concentration 0.2%) Absorption through the skin A = 0.04 µg/cm² Skin Surface Area SSA = 580 cm2 Dermal absorption per treatment SSA x A x 0.001 = 0.0232 mg Typical body weight of human = 60 kg Systemic exposure dose (SED) SSA x A x 0.001/60 = 0.00039 mg/kg bw No observed adverse effect level NOAEL = 3 mg/kg bw/d (90-day, oral, rat) Bioavailability 30%* = 0.9 mg/kg bw/d","page":46,"pdf":"sccs_o_232.pdf","row_type":"noael_study","study_id":"sccs_o_232_noael_016"}
SCCS Opinion NOAEL =0.00039 mg/kg bw rat oral 90-day dermal absorption {"citation":"(ref. 21)","dose":"l NOAEL = 3 mg/kg bw/d (90-day, oral, rat) Bioavailability 30%* = 0.9 mg/kg bw/d Margin of Safety adjusted NOAEL/SED = 1300 * based on the toxicokinetic study (ref.","effect":"l NOAEL = 3 mg/kg bw/d (90-day, oral, rat) Bioavailability 30%* = 0.9 mg/kg bw/d Margin of Safety adjusted NOAEL/SED = 1300 * based on the toxicokinetic study (ref. 21). CALCULATION OF THE MARGIN OF SAFETY (oxidative conditions) (In formulation, on head concentration 0.2%) Absorption through the skin A = 0.04 µg/cm² Skin Surface Area SSA = 580 cm2 Dermal absorption per treatment SSA x A x 0.001 = 0.0232 mg Typical body weight of human = 60 kg Systemic exposure dose (SED) SSA x A x 0.001/60 = 0.00039 mg/kg bw No observed adverse effect level NOAEL = 3 mg/kg bw/d (90-day, oral, rat) Bioavailability 30%* = 0.9 mg/kg bw/d Margin of Safety adjusted NOAEL/SED = 2300 * based on the toxicokinetic study (ref. 21). The above MoS calculations only refer to batch TBFB3/02/30 that was used for the toxicity tests, not the current market quality batches. Because of the large margins of safety (1,300 for non-oxidative conditions and 2,300 for non-oxidative conditions) calculated for the batch TBFB3/02/30, the SCCS has considered that around 2.5 fold relative inc","page":46,"pdf":"sccs_o_232.pdf","row_type":"noael_study","study_id":"sccs_o_232_noael_017"}
SCCS Opinion NOAEL =3 mg/kg bw/day rat oral Sub-chronic repeated dose toxicity {"citation":"Ref.: 2b, subm I 3","dose":"High dose animals showed an increase in white blood cell counts (males) and increases in cholesterol and glucose (females) while at 10 mg/kg bw/day only one male showed a high glucose value.","effect":"treatment-related effects. High dose animals showed an increase in white blood cell counts (males) and increases in cholesterol and glucose (females) while at 10 mg/kg bw/day only one male showed a high glucose value. Discolouration of the caecum related to the staining properties of the test substance was noted in high dose animals. Missing values in male control organ and body weights make it difficult to evaluate possible substance-related changes in absolute and relative body weights. The authors established a NOAEL of 3 mg/kg bw/day. Ref.: 2b, subm I 3.3.5.2. Sub-chronic (90 days) toxicity (oral, dermal) Taken from SCCNFP/0797/04, re-evaluated Guideline: OECD 408 (1998) Species/strain: SPF-bred Wistar rats Group size: 10 males and 10 females per dose group Test substance: Tetrabromophenol Blue dissolved in water containing 5.3% polyglycol 600 and 4.2% of a 50% aqueous decyl glucoside solution Batch: TBFB3/02/30 Purity: 96.7-98.8% Dose levels: 0, 3, 10 and 100 mg/kg bw/day by oral gavage Route: oral gavage GLP: in complian","page":16,"pdf":"sccs_o_101.pdf","row_type":"noael_study","study_id":"sccs_o_101_noael_001"}
SCCS Opinion NOAEL =10 mg/kg bw/day - - 90-day NOAEL study {"citation":"Ref.: 12 Comment The SCCNFP remarked that according to Ref","dose":"and not considered as toxicologically relevant, but changes in platelet values (males) at 100 mg/kg bw/day and changes in erythrocytes counts observed in males which were statistically significant at 10 and 100 mg/kg bw/day point to a haematotoxic potential of the test substance.","effect":"and not considered as toxicologically relevant, but changes in platelet values (males) at 100 mg/kg bw/day and changes in erythrocytes counts observed in males which were statistically significant at 10 and 100 mg/kg bw/day point to a haematotoxic potential of the test substance. Following the dose of 100 mg/kg bw/day changes in urea (males) and cholesterol (females) values were found. Discolouration of the gastro-intestinal tract was observed and related to the staining properties. The study authors established a NOAEL of 10 mg/kg bw/day. Due to the ophthalmological and haematological findings at this dose level, the SCCNFP set the NOAEL to 3 mg/kg bw/day. Ref.: 12 Comment The SCCNFP remarked that according to Ref. 15 (Ref. 5 subm. I), a 2% solution of Tetrabromophenol Blue has not been classified as eye irritating and no corneal opacity was observed at this concentration. However, for the highest dose in this 90-day study 100 mg per kg bw was administered in 5 ml volume per kg, which corresponds to a 2% solution and the observ","page":17,"pdf":"sccs_o_101.pdf","row_type":"noael_study","study_id":"sccs_o_101_noael_002"}
SCCS Opinion NOAEL =50 mg/kg bw/day rat - - NOAEL study {"citation":"Ref.: 17 New study, submission 2005 Guideline: OECD no","dose":"half of the 50 mg/kg dose.","effect":"half of the 50 mg/kg dose. At the low dose 5 mg/kg bw/day a generalised reduction in ossification was seen. Incidental cases of malformations were seen in all dose groups including controls (e.g. polydactyly, exencephaly, spina bifida, abnormal shape of limb bones) but the effects were not dose-related. In the high dose group 18 of 166 analysed foetuses showed changes of the major arteries which should be attributed to treatment. Even in the medium dose one foetus with persistent truncus arteriosus was found. The NOAEL of maternal toxicity was 50 mg/kg bw/day, the NOAEL of teratogenicity was 5 mg/kg bw/day. For embryotoxicity, a NOAEL cannot be established. Ref.: 17 New study, submission 2005 Guideline: OECD no. 414 (2001) Species/strain: Rat, strain Wistar rats HanBrl: WIST, outbred (SPF) Group size: 22 mated females per dose group Test item: Tetrabromophenol Blue Batch: TBFB3/02/30 Purity: 98.8 area % (at 615 nm, HPLC) Dose levels: 0, 3, 30 and 300 mg/kg bw/day Vehicle: 5% w/w polyglycol 600, 4% w/w Plantaren 2000 UP (50% a","page":21,"pdf":"sccs_o_101.pdf","row_type":"noael_study","study_id":"sccs_o_101_noael_004"}
SCCS Opinion NOAEL =5 mg/kg bw/day rat - - NOAEL study {"citation":"Ref.: 17 New study, submission 2005 Guideline: OECD no","dose":"cases of malformations were seen in all dose groups including controls (e.g. polydactyly, exencephaly, spina bifida, abnormal shape of limb bones) but the effects were not dose-related.","effect":"cases of malformations were seen in all dose groups including controls (e.g. polydactyly, exencephaly, spina bifida, abnormal shape of limb bones) but the effects were not dose-related. In the high dose group 18 of 166 analysed foetuses showed changes of the major arteries which should be attributed to treatment. Even in the medium dose one foetus with persistent truncus arteriosus was found. The NOAEL of maternal toxicity was 50 mg/kg bw/day, the NOAEL of teratogenicity was 5 mg/kg bw/day. For embryotoxicity, a NOAEL cannot be established. Ref.: 17 New study, submission 2005 Guideline: OECD no. 414 (2001) Species/strain: Rat, strain Wistar rats HanBrl: WIST, outbred (SPF) Group size: 22 mated females per dose group Test item: Tetrabromophenol Blue Batch: TBFB3/02/30 Purity: 98.8 area % (at 615 nm, HPLC) Dose levels: 0, 3, 30 and 300 mg/kg bw/day Vehicle: 5% w/w polyglycol 600, 4% w/w Plantaren 2000 UP (50% aqueous","page":21,"pdf":"sccs_o_101.pdf","row_type":"noael_study","study_id":"sccs_o_101_noael_006"}
SCCS Opinion NOAEL =30 mg/kg bw/ day rat - - NOAEL study {"citation":"Ref: 18 3","dose":"d incidences of left-sided umbilical arteries and cranially elongated thymuses at the high dose and anophthalmia in the mid dose group.","effect":"d incidences of left-sided umbilical arteries and cranially elongated thymuses at the high dose and anophthalmia in the mid dose group. There was an increased incidence of fused zygomatic arches at the high dose (21 in 12 litters) when compared with the control group (12 in 9 litters). A statistically significant increase in supernumerary rudimentary ribs was observed in the mid and high doses. No changes were noted in the foetuses of the low dose group (3 mg/kg bw). Conclusion Based on these results the maternal NOAEL was considered to be 30 mg/kg bw/ day. A NOAEL for embryo-foetal effects was derived at 3 mg/kg bw/day. Ref: 18 3.3.9. Toxicokinetics Guideline: OECD 417 (1984) and OECD 427 (2004) Species/strain: Rat, Wistar CRL: WI BR (outbreed) (SPF) Group size: Females, mass balance groups (groups 1,2,3,4) 4 per dose; toxicokinetics groups (groups 5, 6, 7, 8) 6 per dose Test substances: Tetrabromophenol Blue-(Phenol-UL-14C) Batch: 064K9418 non-labelled Tetrabromophenol Blue Batch: TBFB3/02/30 Purity: Radiochemical purity: 88","page":23,"pdf":"sccs_o_101.pdf","row_type":"noael_study","study_id":"sccs_o_101_noael_007"}
SCCS Opinion NOAEL =0.0434 mg/kg bw/d rat oral sub-chronic repeated dose toxicity {"citation":"(Ref. 21)","dose":"Safety evaluation (including calculation of the MoS) CALCULATION OF THE MARGIN OF SAFETY INCI Name Non oxidative conditions Absorption through the skin A = 4.49 µg/cm2 Skin Area surface SAS = 580 cm2 Dermal absorption per treatment SAS x A x 0.001 = 2.60 mg Typical body weight of human = 60 kg Systemic exposure dose SAS x A x 0.001/60 = 0.0434 m...","effect":"SCCS/1426/11 Opinion on Tetrabromophenol Blue ___________________________________________________________________________________________ 26 3.3.13. Safety evaluation (including calculation of the MoS) CALCULATION OF THE MARGIN OF SAFETY INCI Name Non oxidative conditions Absorption through the skin A = 4.49 µg/cm2 Skin Area surface SAS = 580 cm2 Dermal absorption per treatment SAS x A x 0.001 = 2.60 mg Typical body weight of human = 60 kg Systemic exposure dose SAS x A x 0.001/60 = 0.0434 mg/kg bw/d No Observed Adverse Effect Level NOAEL = 3 mg/kg bw/d (rat, oral, teratogenicity and sub-chronic toxicity) Corrected for 30% oral bio-availability (Ref. 21) = 0.9 mg/kg bw/d MOS = 21 3.3.14. Discussion Physico-chemical properties Tetrabromophenol Blue is used in oxidative- as well as in non-oxidative hair dye formulations at a maximum concentration of 0.2% on the scalp. The name Tetrabromophenol Blue of the test material is misleading, since the main component is an octabromo-derivative (42%, quantitative HPLC analysis using standard referen","page":26,"pdf":"sccs_o_101.pdf","row_type":"noael_study","study_id":"sccs_o_101_noael_009"}
SCCS Opinion NOAEL =4 - human - - genotoxicity {"effect":"crease of the major components, homologue (4) and (5) in batch 7215600060 by maximally 2.49 fold versus batch TBFB2/02/30 is covered. This is supported by (a) the absence of in vitro genotoxicity in the Ames Test and the In Vitro Human Lymphocyte Micronucleus Assay (b) the absence of skin and mucous membrane irritation or skin sensitization properties of batch TBFB2/02/30 at concentrations 10 fold above use condition (c) a MoS of 529 and 923 for non-oxidative and oxidative conditions, respectively, when the lowest NOAEL for batch TBFB2/02/30 was adjusted for the increases in the two major components of batch 7215600060","page":12,"pdf":"sccs_o_232.pdf","row_type":"noael_study","study_id":"sccs_o_232_noael_001"}
SCCS Opinion NOAEL =100 mg/kg bw/day - - 90-day NOAEL study {"citation":"Ref.: 1 (Submission I) Ref","dose":"rocytes counts observed in males which were statistically significant at 10 and 100 mg/kg bw/day point to a haematotoxic potential of the test substance.","effect":"rocytes counts observed in males which were statistically significant at 10 and 100 mg/kg bw/day point to a haematotoxic potential of the test substance. Following the dose of 100 mg/kg bw/day changes in urea (males) and cholesterol (females) values were found. Discolouration of the gastro-intestinal tract was observed, related to the staining properties. No treatment-related changes were observed in organ weights or in the histopathological examination of organs and tissues. The study report authors established a NOAEL of 100 mg/kg bw/day. Due to the ophthalmological and haematological findings at this dose level, the SCCNFP set the NOAEL to 3 mg/kg bw/day. Ref.: 1 (Submission I) Ref.: 1 (Submission II) SCCS comment The SCCNFP remarked that according to Ref. 15 (Ref. 5 subm. I), a 2% solution of Tetrabromophenol Blue has not been classified as eye irritating and no corneal opacity was observed at this concentration. However, for the highest dose in this 90-day study, 100 mg per kg bw was administered in 5 ml volume per kg, whi","page":31,"pdf":"sccs_o_232.pdf","row_type":"noael_study","study_id":"sccs_o_232_noael_002"}
SCCS Opinion NOAEL =0.00068 mg/kg bw rat oral 90-day dermal absorption {"citation":"(ref. 21)","dose":"Opinion on hair dye Tetrabromophenol Blue, 4,4’-(4,5,6,7-tetrabromo-1,1-dioxido-3H-2,1-benzoxathiol-3-yliden)bis- 2,6-dibromophenol (C183) – Submission IV _____________________________________________________________________________________________________________________ 46 Absorption through the skin A = 0.07 µg/cm² Skin Surface Area SSA = 580...","effect":"Opinion on hair dye Tetrabromophenol Blue, 4,4’-(4,5,6,7-tetrabromo-1,1-dioxido-3H-2,1-benzoxathiol-3-yliden)bis- 2,6-dibromophenol (C183) – Submission IV _____________________________________________________________________________________________________________________ 46 Absorption through the skin A = 0.07 µg/cm² Skin Surface Area SSA = 580 cm2 Dermal absorption per treatment SSA x A x 0.001 = 0.0406 mg Typical body weight of human = 60 kg Systemic exposure dose (SED) SSA x A x 0.001/60 = 0.00068 mg/kg bw No observed adverse effect level NOAEL = 3 mg/kg bw/d (90-day, oral, rat) Bioavailability 30%* = 0.9 mg/kg bw/d Margin of Safety adjusted NOAEL/SED = 1300 * based on the toxicokinetic study (ref. 21). CALCULATION OF THE MARGIN OF SAFETY (oxidative conditions) (In formulation, on head concentration 0.2%) Absorption through the skin A = 0.04 µg/cm² Skin Surface Area SSA = 580 cm2 Dermal absorption per treatment SSA x A x 0.001 = 0.0232 mg Typical body weight of human = 60 kg Systemic exposure dose (SED) SSA x A x 0.001/60 = 0.00039 mg/kg bw N","page":46,"pdf":"sccs_o_232.pdf","row_type":"noael_study","study_id":"sccs_o_232_noael_014"}
SCCS Opinion NOAEL =3 mg/kg bw/d rat oral 90-day dermal absorption {"citation":"(ref. 21)","dose":"henol Blue, 4,4’-(4,5,6,7-tetrabromo-1,1-dioxido-3H-2,1-benzoxathiol-3-yliden)bis- 2,6-dibromophenol (C183) – Submission IV _____________________________________________________________________________________________________________________ 46 Absorption through the skin A = 0.07 µg/cm² Skin Surface Area SSA = 580 cm2 Dermal absorption per trea...","effect":"henol Blue, 4,4’-(4,5,6,7-tetrabromo-1,1-dioxido-3H-2,1-benzoxathiol-3-yliden)bis- 2,6-dibromophenol (C183) – Submission IV _____________________________________________________________________________________________________________________ 46 Absorption through the skin A = 0.07 µg/cm² Skin Surface Area SSA = 580 cm2 Dermal absorption per treatment SSA x A x 0.001 = 0.0406 mg Typical body weight of human = 60 kg Systemic exposure dose (SED) SSA x A x 0.001/60 = 0.00068 mg/kg bw No observed adverse effect level NOAEL = 3 mg/kg bw/d (90-day, oral, rat) Bioavailability 30%* = 0.9 mg/kg bw/d Margin of Safety adjusted NOAEL/SED = 1300 * based on the toxicokinetic study (ref. 21). CALCULATION OF THE MARGIN OF SAFETY (oxidative conditions) (In formulation, on head concentration 0.2%) Absorption through the skin A = 0.04 µg/cm² Skin Surface Area SSA = 580 cm2 Dermal absorption per treatment SSA x A x 0.001 = 0.0232 mg Typical body weight of human = 60 kg Systemic exposure dose (SED) SSA x A x 0.001/60 = 0.00039 mg/kg bw No obse","page":46,"pdf":"sccs_o_232.pdf","row_type":"noael_study","study_id":"sccs_o_232_noael_015"}
SCCS Opinion NOAEL =0.9 mg/kg bw/d rat oral 90-day dermal absorption {"citation":"(ref. 21)","dose":"3) – Submission IV _____________________________________________________________________________________________________________________ 46 Absorption through the skin A = 0.07 µg/cm² Skin Surface Area SSA = 580 cm2 Dermal absorption per treatment SSA x A x 0.001 = 0.0406 mg Typical body weight of human = 60 kg Systemic exposure dose (SED) SSA x...","effect":"3) – Submission IV _____________________________________________________________________________________________________________________ 46 Absorption through the skin A = 0.07 µg/cm² Skin Surface Area SSA = 580 cm2 Dermal absorption per treatment SSA x A x 0.001 = 0.0406 mg Typical body weight of human = 60 kg Systemic exposure dose (SED) SSA x A x 0.001/60 = 0.00068 mg/kg bw No observed adverse effect level NOAEL = 3 mg/kg bw/d (90-day, oral, rat) Bioavailability 30%* = 0.9 mg/kg bw/d Margin of Safety adjusted NOAEL/SED = 1300 * based on the toxicokinetic study (ref. 21). CALCULATION OF THE MARGIN OF SAFETY (oxidative conditions) (In formulation, on head concentration 0.2%) Absorption through the skin A = 0.04 µg/cm² Skin Surface Area SSA = 580 cm2 Dermal absorption per treatment SSA x A x 0.001 = 0.0232 mg Typical body weight of human = 60 kg Systemic exposure dose (SED) SSA x A x 0.001/60 = 0.00039 mg/kg bw No observed adverse effect level NOAEL = 3 mg/kg bw/d (90-day, oral, rat) Bioavailability 30%* = 0.9 mg/kg bw/d","page":46,"pdf":"sccs_o_232.pdf","row_type":"noael_study","study_id":"sccs_o_232_noael_016"}
SCCS Opinion NOAEL =0.00039 mg/kg bw rat oral 90-day dermal absorption {"citation":"(ref. 21)","dose":"l NOAEL = 3 mg/kg bw/d (90-day, oral, rat) Bioavailability 30%* = 0.9 mg/kg bw/d Margin of Safety adjusted NOAEL/SED = 1300 * based on the toxicokinetic study (ref.","effect":"l NOAEL = 3 mg/kg bw/d (90-day, oral, rat) Bioavailability 30%* = 0.9 mg/kg bw/d Margin of Safety adjusted NOAEL/SED = 1300 * based on the toxicokinetic study (ref. 21). CALCULATION OF THE MARGIN OF SAFETY (oxidative conditions) (In formulation, on head concentration 0.2%) Absorption through the skin A = 0.04 µg/cm² Skin Surface Area SSA = 580 cm2 Dermal absorption per treatment SSA x A x 0.001 = 0.0232 mg Typical body weight of human = 60 kg Systemic exposure dose (SED) SSA x A x 0.001/60 = 0.00039 mg/kg bw No observed adverse effect level NOAEL = 3 mg/kg bw/d (90-day, oral, rat) Bioavailability 30%* = 0.9 mg/kg bw/d Margin of Safety adjusted NOAEL/SED = 2300 * based on the toxicokinetic study (ref. 21). The above MoS calculations only refer to batch TBFB3/02/30 that was used for the toxicity tests, not the current market quality batches. Because of the large margins of safety (1,300 for non-oxidative conditions and 2,300 for non-oxidative conditions) calculated for the batch TBFB3/02/30, the SCCS has considered that around 2.5 fold relative inc","page":46,"pdf":"sccs_o_232.pdf","row_type":"noael_study","study_id":"sccs_o_232_noael_017"}
SCCS Opinion NOAEL =0.00039 mg/kg bw rat oral 90-day dermal absorption {"citation":"(ref. 21)","dose":"l NOAEL = 3 mg/kg bw/d (90-day, oral, rat) Bioavailability 30%* = 0.9 mg/kg bw/d Margin of Safety adjusted NOAEL/SED = 1300 * based on the toxicokinetic study (ref.","effect":"l NOAEL = 3 mg/kg bw/d (90-day, oral, rat) Bioavailability 30%* = 0.9 mg/kg bw/d Margin of Safety adjusted NOAEL/SED = 1300 * based on the toxicokinetic study (ref. 21). CALCULATION OF THE MARGIN OF SAFETY (oxidative conditions) (In formulation, on head concentration 0.2%) Absorption through the skin A = 0.04 µg/cm² Skin Area surface SAS = 580 cm2 Dermal absorption per treatment SAS x A x 0.001 = 0.0232 mg Typical body weight of human = 60 kg Systemic exposure dose (SED) SAS x A x 0.001/… = 0.00039 mg/kg bw No observed adverse effect level NOAEL = 3 mg/kg bw/d (90-day, oral, rat) Bioavailability 30%* = 0.9 mg/kg bw/d Margin of Safety adjusted NOAEL/SED = 2300 * based on the toxicokinetic study (ref. 21). 3.3.14 Discussion Physicochemical properties Tetrabromophenol Blue is used in oxidative- as well as in non-oxidative hair dye formulations at a maximum concentration of 0.2% on the scalp. The test material is not composed of a single substance. Although the main component is octabromo derivative of phenolsulfonphthalein, the material also conta","page":34,"pdf":"sccs_o_197.pdf","row_type":"noael_study","study_id":"sccs_o_197_noael_015"}
SCCS Opinion NOAEL =0.00039 mg/kg bw rat oral 90-day dermal absorption {"citation":"(ref. 21)","dose":"l NOAEL = 3 mg/kg bw/d (90-day, oral, rat) Bioavailability 30%* = 0.9 mg/kg bw/d Margin of Safety adjusted NOAEL/SED = 1300 * based on the toxicokinetic study (ref.","effect":"l NOAEL = 3 mg/kg bw/d (90-day, oral, rat) Bioavailability 30%* = 0.9 mg/kg bw/d Margin of Safety adjusted NOAEL/SED = 1300 * based on the toxicokinetic study (ref. 21). CALCULATION OF THE MARGIN OF SAFETY (oxidative conditions) (In formulation, on head concentration 0.2%) Absorption through the skin A = 0.04 µg/cm² Skin Area surface SAS = 580 cm2 Dermal absorption per treatment SAS x A x 0.001 = 0.0232 mg Typical body weight of human = 60 kg Systemic exposure dose (SED) SAS x A x 0.001/… = 0.00039 mg/kg bw No observed adverse effect level NOAEL = 3 mg/kg bw/d (90-day, oral, rat) Bioavailability 30%* = 0.9 mg/kg bw/d Margin of Safety adjusted NOAEL/SED = 2300 * based on the toxicokinetic study (ref. 21). 3.3.14 Discussion Physicochemical properties Tetrabromophenol Blue is used in oxidative- as well as in non-oxidative hair dye formulations at a maximum concentration of 0.2% on the scalp. The test material is not composed of a single substance. Although the main component is octabromo derivative of phenolsulfonphthalein, the material also conta","page":34,"pdf":"sccs_o_197.pdf","row_type":"noael_study","study_id":"sccs_o_197_noael_015"}
SCCS Opinion NOAEL =0.00039 mg/kg bw rat oral 90-day dermal absorption {"citation":"(ref. 21)","dose":"l NOAEL = 3 mg/kg bw/d (90-day, oral, rat) Bioavailability 30%* = 0.9 mg/kg bw/d Margin of Safety adjusted NOAEL/SED = 1300 * based on the toxicokinetic study (ref.","effect":"l NOAEL = 3 mg/kg bw/d (90-day, oral, rat) Bioavailability 30%* = 0.9 mg/kg bw/d Margin of Safety adjusted NOAEL/SED = 1300 * based on the toxicokinetic study (ref. 21). CALCULATION OF THE MARGIN OF SAFETY (oxidative conditions) (In formulation, on head concentration 0.2%) Absorption through the skin A = 0.04 µg/cm² Skin Area surface SAS = 580 cm2 Dermal absorption per treatment SAS x A x 0.001 = 0.0232 mg Typical body weight of human = 60 kg Systemic exposure dose (SED) SAS x A x 0.001/… = 0.00039 mg/kg bw No observed adverse effect level NOAEL = 3 mg/kg bw/d (90-day, oral, rat) Bioavailability 30%* = 0.9 mg/kg bw/d Margin of Safety adjusted NOAEL/SED = 2300 * based on the toxicokinetic study (ref. 21). 3.3.14 Discussion Physicochemical properties Tetrabromophenol Blue is used in oxidative- as well as in non-oxidative hair dye formulations at a maximum concentration of 0.2% on the scalp. The test material is not composed of a single substance. Although the main component is octabromo derivative of phenolsulfonphthalein, the material also conta","page":34,"pdf":"sccs_o_197.pdf","row_type":"noael_study","study_id":"sccs_o_197_noael_015"}
SCCS Opinion NOAEL =0.00039 mg/kg bw rat oral 90-day dermal absorption {"citation":"(ref. 21)","dose":"l NOAEL = 3 mg/kg bw/d (90-day, oral, rat) Bioavailability 30%* = 0.9 mg/kg bw/d Margin of Safety adjusted NOAEL/SED = 1300 * based on the toxicokinetic study (ref.","effect":"l NOAEL = 3 mg/kg bw/d (90-day, oral, rat) Bioavailability 30%* = 0.9 mg/kg bw/d Margin of Safety adjusted NOAEL/SED = 1300 * based on the toxicokinetic study (ref. 21). CALCULATION OF THE MARGIN OF SAFETY (oxidative conditions) (In formulation, on head concentration 0.2%) Absorption through the skin A = 0.04 µg/cm² Skin Area surface SAS = 580 cm2 Dermal absorption per treatment SAS x A x 0.001 = 0.0232 mg Typical body weight of human = 60 kg Systemic exposure dose (SED) SAS x A x 0.001/… = 0.00039 mg/kg bw No observed adverse effect level NOAEL = 3 mg/kg bw/d (90-day, oral, rat) Bioavailability 30%* = 0.9 mg/kg bw/d Margin of Safety adjusted NOAEL/SED = 2300 * based on the toxicokinetic study (ref. 21). 3.3.14 Discussion Physicochemical properties Tetrabromophenol Blue is used in oxidative- as well as in non-oxidative hair dye formulations at a maximum concentration of 0.2% on the scalp. The test material is not composed of a single substance. Although the main component is octabromo derivative of phenolsulfonphthalein, the material also conta","page":34,"pdf":"sccs_o_197.pdf","row_type":"noael_study","study_id":"sccs_o_197_noael_015"}
SCCS Opinion NOAEL =0.00068 mg/kg bw rat oral 90-day dermal absorption {"citation":"(ref. 21)","dose":"o-1,1-dioxido-3H-2,1-benzoxathiol-3-yliden)bis- 2,6-dibromophenol (C183) ___________________________________________________________________________________________ 34 CALCULATION OF THE MARGIN OF SAFETY (non-oxidative conditions) (In formulation, on head concentration 0.2%) Absorption through the skin A = 0.07 µg/cm² Skin Area surface SAS = 580...","effect":"o-1,1-dioxido-3H-2,1-benzoxathiol-3-yliden)bis- 2,6-dibromophenol (C183) ___________________________________________________________________________________________ 34 CALCULATION OF THE MARGIN OF SAFETY (non-oxidative conditions) (In formulation, on head concentration 0.2%) Absorption through the skin A = 0.07 µg/cm² Skin Area surface SAS = 580 cm2 Dermal absorption per treatment SAS x A x 0.001 = 0.0406 mg Typical body weight of human = 60 kg Systemic exposure dose (SED) SAS x A x 0.001/… = 0.00068 mg/kg bw No observed adverse effect level NOAEL = 3 mg/kg bw/d (90-day, oral, rat) Bioavailability 30%* = 0.9 mg/kg bw/d Margin of Safety adjusted NOAEL/SED = 1300 * based on the toxicokinetic study (ref. 21). CALCULATION OF THE MARGIN OF SAFETY (oxidative conditions) (In formulation, on head concentration 0.2%) Absorption through the skin A = 0.04 µg/cm² Skin Area surface SAS = 580 cm2 Dermal absorption per treatment SAS x A x 0.001 = 0.0232 mg Typical body weight of human = 60 kg Systemic exposure dose (SED) SAS x A x 0.001/… = 0.00039 mg/kg bw N","page":34,"pdf":"sccs_o_197.pdf","row_type":"noael_study","study_id":"sccs_o_197_noael_012"}
SCCS Opinion NOAEL =0.00068 mg/kg bw rat oral 90-day dermal absorption {"citation":"(ref. 21)","dose":"o-1,1-dioxido-3H-2,1-benzoxathiol-3-yliden)bis- 2,6-dibromophenol (C183) ___________________________________________________________________________________________ 34 CALCULATION OF THE MARGIN OF SAFETY (non-oxidative conditions) (In formulation, on head concentration 0.2%) Absorption through the skin A = 0.07 µg/cm² Skin Area surface SAS = 580...","effect":"o-1,1-dioxido-3H-2,1-benzoxathiol-3-yliden)bis- 2,6-dibromophenol (C183) ___________________________________________________________________________________________ 34 CALCULATION OF THE MARGIN OF SAFETY (non-oxidative conditions) (In formulation, on head concentration 0.2%) Absorption through the skin A = 0.07 µg/cm² Skin Area surface SAS = 580 cm2 Dermal absorption per treatment SAS x A x 0.001 = 0.0406 mg Typical body weight of human = 60 kg Systemic exposure dose (SED) SAS x A x 0.001/… = 0.00068 mg/kg bw No observed adverse effect level NOAEL = 3 mg/kg bw/d (90-day, oral, rat) Bioavailability 30%* = 0.9 mg/kg bw/d Margin of Safety adjusted NOAEL/SED = 1300 * based on the toxicokinetic study (ref. 21). CALCULATION OF THE MARGIN OF SAFETY (oxidative conditions) (In formulation, on head concentration 0.2%) Absorption through the skin A = 0.04 µg/cm² Skin Area surface SAS = 580 cm2 Dermal absorption per treatment SAS x A x 0.001 = 0.0232 mg Typical body weight of human = 60 kg Systemic exposure dose (SED) SAS x A x 0.001/… = 0.00039 mg/kg bw N","page":34,"pdf":"sccs_o_197.pdf","row_type":"noael_study","study_id":"sccs_o_197_noael_012"}
SCCS Opinion NOAEL =0.00068 mg/kg bw rat oral 90-day dermal absorption {"citation":"(ref. 21)","dose":"o-1,1-dioxido-3H-2,1-benzoxathiol-3-yliden)bis- 2,6-dibromophenol (C183) ___________________________________________________________________________________________ 34 CALCULATION OF THE MARGIN OF SAFETY (non-oxidative conditions) (In formulation, on head concentration 0.2%) Absorption through the skin A = 0.07 µg/cm² Skin Area surface SAS = 580...","effect":"o-1,1-dioxido-3H-2,1-benzoxathiol-3-yliden)bis- 2,6-dibromophenol (C183) ___________________________________________________________________________________________ 34 CALCULATION OF THE MARGIN OF SAFETY (non-oxidative conditions) (In formulation, on head concentration 0.2%) Absorption through the skin A = 0.07 µg/cm² Skin Area surface SAS = 580 cm2 Dermal absorption per treatment SAS x A x 0.001 = 0.0406 mg Typical body weight of human = 60 kg Systemic exposure dose (SED) SAS x A x 0.001/… = 0.00068 mg/kg bw No observed adverse effect level NOAEL = 3 mg/kg bw/d (90-day, oral, rat) Bioavailability 30%* = 0.9 mg/kg bw/d Margin of Safety adjusted NOAEL/SED = 1300 * based on the toxicokinetic study (ref. 21). CALCULATION OF THE MARGIN OF SAFETY (oxidative conditions) (In formulation, on head concentration 0.2%) Absorption through the skin A = 0.04 µg/cm² Skin Area surface SAS = 580 cm2 Dermal absorption per treatment SAS x A x 0.001 = 0.0232 mg Typical body weight of human = 60 kg Systemic exposure dose (SED) SAS x A x 0.001/… = 0.00039 mg/kg bw N","page":34,"pdf":"sccs_o_197.pdf","row_type":"noael_study","study_id":"sccs_o_197_noael_012"}
SCCS Opinion NOAEL =0.00068 mg/kg bw rat oral 90-day dermal absorption {"citation":"(ref. 21)","dose":"o-1,1-dioxido-3H-2,1-benzoxathiol-3-yliden)bis- 2,6-dibromophenol (C183) ___________________________________________________________________________________________ 34 CALCULATION OF THE MARGIN OF SAFETY (non-oxidative conditions) (In formulation, on head concentration 0.2%) Absorption through the skin A = 0.07 µg/cm² Skin Area surface SAS = 580...","effect":"o-1,1-dioxido-3H-2,1-benzoxathiol-3-yliden)bis- 2,6-dibromophenol (C183) ___________________________________________________________________________________________ 34 CALCULATION OF THE MARGIN OF SAFETY (non-oxidative conditions) (In formulation, on head concentration 0.2%) Absorption through the skin A = 0.07 µg/cm² Skin Area surface SAS = 580 cm2 Dermal absorption per treatment SAS x A x 0.001 = 0.0406 mg Typical body weight of human = 60 kg Systemic exposure dose (SED) SAS x A x 0.001/… = 0.00068 mg/kg bw No observed adverse effect level NOAEL = 3 mg/kg bw/d (90-day, oral, rat) Bioavailability 30%* = 0.9 mg/kg bw/d Margin of Safety adjusted NOAEL/SED = 1300 * based on the toxicokinetic study (ref. 21). CALCULATION OF THE MARGIN OF SAFETY (oxidative conditions) (In formulation, on head concentration 0.2%) Absorption through the skin A = 0.04 µg/cm² Skin Area surface SAS = 580 cm2 Dermal absorption per treatment SAS x A x 0.001 = 0.0232 mg Typical body weight of human = 60 kg Systemic exposure dose (SED) SAS x A x 0.001/… = 0.00039 mg/kg bw N","page":34,"pdf":"sccs_o_197.pdf","row_type":"noael_study","study_id":"sccs_o_197_noael_012"}
SCCS Opinion NOAEL =0.9 mg/kg bw/d rat oral 90-day dermal absorption {"citation":"(ref. 21)","dose":"_________________________ 34 CALCULATION OF THE MARGIN OF SAFETY (non-oxidative conditions) (In formulation, on head concentration 0.2%) Absorption through the skin A = 0.07 µg/cm² Skin Area surface SAS = 580 cm2 Dermal absorption per treatment SAS x A x 0.001 = 0.0406 mg Typical body weight of human = 60 kg Systemic exposure dose (SED) SAS x A...","effect":"_________________________ 34 CALCULATION OF THE MARGIN OF SAFETY (non-oxidative conditions) (In formulation, on head concentration 0.2%) Absorption through the skin A = 0.07 µg/cm² Skin Area surface SAS = 580 cm2 Dermal absorption per treatment SAS x A x 0.001 = 0.0406 mg Typical body weight of human = 60 kg Systemic exposure dose (SED) SAS x A x 0.001/… = 0.00068 mg/kg bw No observed adverse effect level NOAEL = 3 mg/kg bw/d (90-day, oral, rat) Bioavailability 30%* = 0.9 mg/kg bw/d Margin of Safety adjusted NOAEL/SED = 1300 * based on the toxicokinetic study (ref. 21). CALCULATION OF THE MARGIN OF SAFETY (oxidative conditions) (In formulation, on head concentration 0.2%) Absorption through the skin A = 0.04 µg/cm² Skin Area surface SAS = 580 cm2 Dermal absorption per treatment SAS x A x 0.001 = 0.0232 mg Typical body weight of human = 60 kg Systemic exposure dose (SED) SAS x A x 0.001/… = 0.00039 mg/kg bw No observed adverse effect level NOAEL = 3 mg/kg bw/d (90-day, oral, rat) Bioavailability 30%* = 0.9 mg/kg bw/d","page":34,"pdf":"sccs_o_197.pdf","row_type":"noael_study","study_id":"sccs_o_197_noael_014"}
SCCS Opinion NOAEL =0.9 mg/kg bw/d rat oral 90-day dermal absorption {"citation":"(ref. 21)","dose":"_________________________ 34 CALCULATION OF THE MARGIN OF SAFETY (non-oxidative conditions) (In formulation, on head concentration 0.2%) Absorption through the skin A = 0.07 µg/cm² Skin Area surface SAS = 580 cm2 Dermal absorption per treatment SAS x A x 0.001 = 0.0406 mg Typical body weight of human = 60 kg Systemic exposure dose (SED) SAS x A...","effect":"_________________________ 34 CALCULATION OF THE MARGIN OF SAFETY (non-oxidative conditions) (In formulation, on head concentration 0.2%) Absorption through the skin A = 0.07 µg/cm² Skin Area surface SAS = 580 cm2 Dermal absorption per treatment SAS x A x 0.001 = 0.0406 mg Typical body weight of human = 60 kg Systemic exposure dose (SED) SAS x A x 0.001/… = 0.00068 mg/kg bw No observed adverse effect level NOAEL = 3 mg/kg bw/d (90-day, oral, rat) Bioavailability 30%* = 0.9 mg/kg bw/d Margin of Safety adjusted NOAEL/SED = 1300 * based on the toxicokinetic study (ref. 21). CALCULATION OF THE MARGIN OF SAFETY (oxidative conditions) (In formulation, on head concentration 0.2%) Absorption through the skin A = 0.04 µg/cm² Skin Area surface SAS = 580 cm2 Dermal absorption per treatment SAS x A x 0.001 = 0.0232 mg Typical body weight of human = 60 kg Systemic exposure dose (SED) SAS x A x 0.001/… = 0.00039 mg/kg bw No observed adverse effect level NOAEL = 3 mg/kg bw/d (90-day, oral, rat) Bioavailability 30%* = 0.9 mg/kg bw/d","page":34,"pdf":"sccs_o_197.pdf","row_type":"noael_study","study_id":"sccs_o_197_noael_014"}
SCCS Opinion NOAEL =0.9 mg/kg bw/d rat oral 90-day dermal absorption {"citation":"(ref. 21)","dose":"_________________________ 34 CALCULATION OF THE MARGIN OF SAFETY (non-oxidative conditions) (In formulation, on head concentration 0.2%) Absorption through the skin A = 0.07 µg/cm² Skin Area surface SAS = 580 cm2 Dermal absorption per treatment SAS x A x 0.001 = 0.0406 mg Typical body weight of human = 60 kg Systemic exposure dose (SED) SAS x A...","effect":"_________________________ 34 CALCULATION OF THE MARGIN OF SAFETY (non-oxidative conditions) (In formulation, on head concentration 0.2%) Absorption through the skin A = 0.07 µg/cm² Skin Area surface SAS = 580 cm2 Dermal absorption per treatment SAS x A x 0.001 = 0.0406 mg Typical body weight of human = 60 kg Systemic exposure dose (SED) SAS x A x 0.001/… = 0.00068 mg/kg bw No observed adverse effect level NOAEL = 3 mg/kg bw/d (90-day, oral, rat) Bioavailability 30%* = 0.9 mg/kg bw/d Margin of Safety adjusted NOAEL/SED = 1300 * based on the toxicokinetic study (ref. 21). CALCULATION OF THE MARGIN OF SAFETY (oxidative conditions) (In formulation, on head concentration 0.2%) Absorption through the skin A = 0.04 µg/cm² Skin Area surface SAS = 580 cm2 Dermal absorption per treatment SAS x A x 0.001 = 0.0232 mg Typical body weight of human = 60 kg Systemic exposure dose (SED) SAS x A x 0.001/… = 0.00039 mg/kg bw No observed adverse effect level NOAEL = 3 mg/kg bw/d (90-day, oral, rat) Bioavailability 30%* = 0.9 mg/kg bw/d","page":34,"pdf":"sccs_o_197.pdf","row_type":"noael_study","study_id":"sccs_o_197_noael_014"}
SCCS Opinion NOAEL =0.9 mg/kg bw/d rat oral 90-day dermal absorption {"citation":"(ref. 21)","dose":"_________________________ 34 CALCULATION OF THE MARGIN OF SAFETY (non-oxidative conditions) (In formulation, on head concentration 0.2%) Absorption through the skin A = 0.07 µg/cm² Skin Area surface SAS = 580 cm2 Dermal absorption per treatment SAS x A x 0.001 = 0.0406 mg Typical body weight of human = 60 kg Systemic exposure dose (SED) SAS x A...","effect":"_________________________ 34 CALCULATION OF THE MARGIN OF SAFETY (non-oxidative conditions) (In formulation, on head concentration 0.2%) Absorption through the skin A = 0.07 µg/cm² Skin Area surface SAS = 580 cm2 Dermal absorption per treatment SAS x A x 0.001 = 0.0406 mg Typical body weight of human = 60 kg Systemic exposure dose (SED) SAS x A x 0.001/… = 0.00068 mg/kg bw No observed adverse effect level NOAEL = 3 mg/kg bw/d (90-day, oral, rat) Bioavailability 30%* = 0.9 mg/kg bw/d Margin of Safety adjusted NOAEL/SED = 1300 * based on the toxicokinetic study (ref. 21). CALCULATION OF THE MARGIN OF SAFETY (oxidative conditions) (In formulation, on head concentration 0.2%) Absorption through the skin A = 0.04 µg/cm² Skin Area surface SAS = 580 cm2 Dermal absorption per treatment SAS x A x 0.001 = 0.0232 mg Typical body weight of human = 60 kg Systemic exposure dose (SED) SAS x A x 0.001/… = 0.00039 mg/kg bw No observed adverse effect level NOAEL = 3 mg/kg bw/d (90-day, oral, rat) Bioavailability 30%* = 0.9 mg/kg bw/d","page":34,"pdf":"sccs_o_197.pdf","row_type":"noael_study","study_id":"sccs_o_197_noael_014"}
SCCS Opinion NOAEL =3 mg/kg bw/day - - 90-day NOAEL study {"citation":"Ref.: 12 Comment The SCCNFP remarked that according to Ref","dose":"Following the dose of 100 mg/kg bw/day changes in urea (males) and cholesterol (females) values were found.","effect":"ntial of the test substance. Following the dose of 100 mg/kg bw/day changes in urea (males) and cholesterol (females) values were found. Discolouration of the gastro-intestinal tract was observed and related to the staining properties. No treatment-related changes were observed in organ weights or in the histopathological examination of organs and tissues. The study report authors established a NOAEL of 100 mg/kg bw/day. Due to the ophthalmological and haematological findings at this dose level, the SCCNFP set the NOAEL to 3 mg/kg bw/day. Ref.: 12 Comment The SCCNFP remarked that according to Ref. 15 (Ref. 5 subm. I), a 2% solution of Tetrabromophenol Blue has not been classified as eye irritating and no corneal opacity was observed at this concentration. However, for the highest dose in this 90-day study, 100 mg per kg bw was administered in 5 ml volume per kg, which corresponds to a 2% solution and the observed ophthalmological effects were attributed to direct eye contact. Reassessment by the SCCS In 2004, only a draft stud","page":23,"pdf":"sccs_o_197.pdf","row_type":"noael_study","study_id":"sccs_o_197_noael_002"}
SCCS Opinion NOAEL =3 mg/kg bw/d rat oral 90-day dermal absorption {"citation":"(ref. 21)","dose":"-3-yliden)bis- 2,6-dibromophenol (C183) ___________________________________________________________________________________________ 34 CALCULATION OF THE MARGIN OF SAFETY (non-oxidative conditions) (In formulation, on head concentration 0.2%) Absorption through the skin A = 0.07 µg/cm² Skin Area surface SAS = 580 cm2 Dermal absorption per treatm...","effect":"-3-yliden)bis- 2,6-dibromophenol (C183) ___________________________________________________________________________________________ 34 CALCULATION OF THE MARGIN OF SAFETY (non-oxidative conditions) (In formulation, on head concentration 0.2%) Absorption through the skin A = 0.07 µg/cm² Skin Area surface SAS = 580 cm2 Dermal absorption per treatment SAS x A x 0.001 = 0.0406 mg Typical body weight of human = 60 kg Systemic exposure dose (SED) SAS x A x 0.001/… = 0.00068 mg/kg bw No observed adverse effect level NOAEL = 3 mg/kg bw/d (90-day, oral, rat) Bioavailability 30%* = 0.9 mg/kg bw/d Margin of Safety adjusted NOAEL/SED = 1300 * based on the toxicokinetic study (ref. 21). CALCULATION OF THE MARGIN OF SAFETY (oxidative conditions) (In formulation, on head concentration 0.2%) Absorption through the skin A = 0.04 µg/cm² Skin Area surface SAS = 580 cm2 Dermal absorption per treatment SAS x A x 0.001 = 0.0232 mg Typical body weight of human = 60 kg Systemic exposure dose (SED) SAS x A x 0.001/… = 0.00039 mg/kg bw No obse","page":34,"pdf":"sccs_o_197.pdf","row_type":"noael_study","study_id":"sccs_o_197_noael_013"}
SCCS Opinion NOAEL =3 mg/kg bw/day - - 90-day NOAEL study {"citation":"Ref.: 12 Comment The SCCNFP remarked that according to Ref","dose":"Following the dose of 100 mg/kg bw/day changes in urea (males) and cholesterol (females) values were found.","effect":"ntial of the test substance. Following the dose of 100 mg/kg bw/day changes in urea (males) and cholesterol (females) values were found. Discolouration of the gastro-intestinal tract was observed and related to the staining properties. No treatment-related changes were observed in organ weights or in the histopathological examination of organs and tissues. The study report authors established a NOAEL of 100 mg/kg bw/day. Due to the ophthalmological and haematological findings at this dose level, the SCCNFP set the NOAEL to 3 mg/kg bw/day. Ref.: 12 Comment The SCCNFP remarked that according to Ref. 15 (Ref. 5 subm. I), a 2% solution of Tetrabromophenol Blue has not been classified as eye irritating and no corneal opacity was observed at this concentration. However, for the highest dose in this 90-day study, 100 mg per kg bw was administered in 5 ml volume per kg, which corresponds to a 2% solution and the observed ophthalmological effects were attributed to direct eye contact. Reassessment by the SCCS In 2004, only a draft stud","page":23,"pdf":"sccs_o_197.pdf","row_type":"noael_study","study_id":"sccs_o_197_noael_002"}
SCCS Opinion NOAEL =3 mg/kg bw/d rat oral 90-day dermal absorption {"citation":"(ref. 21)","dose":"-3-yliden)bis- 2,6-dibromophenol (C183) ___________________________________________________________________________________________ 34 CALCULATION OF THE MARGIN OF SAFETY (non-oxidative conditions) (In formulation, on head concentration 0.2%) Absorption through the skin A = 0.07 µg/cm² Skin Area surface SAS = 580 cm2 Dermal absorption per treatm...","effect":"-3-yliden)bis- 2,6-dibromophenol (C183) ___________________________________________________________________________________________ 34 CALCULATION OF THE MARGIN OF SAFETY (non-oxidative conditions) (In formulation, on head concentration 0.2%) Absorption through the skin A = 0.07 µg/cm² Skin Area surface SAS = 580 cm2 Dermal absorption per treatment SAS x A x 0.001 = 0.0406 mg Typical body weight of human = 60 kg Systemic exposure dose (SED) SAS x A x 0.001/… = 0.00068 mg/kg bw No observed adverse effect level NOAEL = 3 mg/kg bw/d (90-day, oral, rat) Bioavailability 30%* = 0.9 mg/kg bw/d Margin of Safety adjusted NOAEL/SED = 1300 * based on the toxicokinetic study (ref. 21). CALCULATION OF THE MARGIN OF SAFETY (oxidative conditions) (In formulation, on head concentration 0.2%) Absorption through the skin A = 0.04 µg/cm² Skin Area surface SAS = 580 cm2 Dermal absorption per treatment SAS x A x 0.001 = 0.0232 mg Typical body weight of human = 60 kg Systemic exposure dose (SED) SAS x A x 0.001/… = 0.00039 mg/kg bw No obse","page":34,"pdf":"sccs_o_197.pdf","row_type":"noael_study","study_id":"sccs_o_197_noael_013"}
SCCS Opinion NOAEL =3 mg/kg bw/day - - 90-day NOAEL study {"citation":"Ref.: 12 Comment The SCCNFP remarked that according to Ref","dose":"Following the dose of 100 mg/kg bw/day changes in urea (males) and cholesterol (females) values were found.","effect":"ntial of the test substance. Following the dose of 100 mg/kg bw/day changes in urea (males) and cholesterol (females) values were found. Discolouration of the gastro-intestinal tract was observed and related to the staining properties. No treatment-related changes were observed in organ weights or in the histopathological examination of organs and tissues. The study report authors established a NOAEL of 100 mg/kg bw/day. Due to the ophthalmological and haematological findings at this dose level, the SCCNFP set the NOAEL to 3 mg/kg bw/day. Ref.: 12 Comment The SCCNFP remarked that according to Ref. 15 (Ref. 5 subm. I), a 2% solution of Tetrabromophenol Blue has not been classified as eye irritating and no corneal opacity was observed at this concentration. However, for the highest dose in this 90-day study, 100 mg per kg bw was administered in 5 ml volume per kg, which corresponds to a 2% solution and the observed ophthalmological effects were attributed to direct eye contact. Reassessment by the SCCS In 2004, only a draft stud","page":23,"pdf":"sccs_o_197.pdf","row_type":"noael_study","study_id":"sccs_o_197_noael_002"}
SCCS Opinion NOAEL =3 mg/kg bw/d rat oral 90-day dermal absorption {"citation":"(ref. 21)","dose":"-3-yliden)bis- 2,6-dibromophenol (C183) ___________________________________________________________________________________________ 34 CALCULATION OF THE MARGIN OF SAFETY (non-oxidative conditions) (In formulation, on head concentration 0.2%) Absorption through the skin A = 0.07 µg/cm² Skin Area surface SAS = 580 cm2 Dermal absorption per treatm...","effect":"-3-yliden)bis- 2,6-dibromophenol (C183) ___________________________________________________________________________________________ 34 CALCULATION OF THE MARGIN OF SAFETY (non-oxidative conditions) (In formulation, on head concentration 0.2%) Absorption through the skin A = 0.07 µg/cm² Skin Area surface SAS = 580 cm2 Dermal absorption per treatment SAS x A x 0.001 = 0.0406 mg Typical body weight of human = 60 kg Systemic exposure dose (SED) SAS x A x 0.001/… = 0.00068 mg/kg bw No observed adverse effect level NOAEL = 3 mg/kg bw/d (90-day, oral, rat) Bioavailability 30%* = 0.9 mg/kg bw/d Margin of Safety adjusted NOAEL/SED = 1300 * based on the toxicokinetic study (ref. 21). CALCULATION OF THE MARGIN OF SAFETY (oxidative conditions) (In formulation, on head concentration 0.2%) Absorption through the skin A = 0.04 µg/cm² Skin Area surface SAS = 580 cm2 Dermal absorption per treatment SAS x A x 0.001 = 0.0232 mg Typical body weight of human = 60 kg Systemic exposure dose (SED) SAS x A x 0.001/… = 0.00039 mg/kg bw No obse","page":34,"pdf":"sccs_o_197.pdf","row_type":"noael_study","study_id":"sccs_o_197_noael_013"}
SCCS Opinion NOAEL =3 mg/kg bw/day - - 90-day NOAEL study {"citation":"Ref.: 12 Comment The SCCNFP remarked that according to Ref","dose":"Following the dose of 100 mg/kg bw/day changes in urea (males) and cholesterol (females) values were found.","effect":"ntial of the test substance. Following the dose of 100 mg/kg bw/day changes in urea (males) and cholesterol (females) values were found. Discolouration of the gastro-intestinal tract was observed and related to the staining properties. No treatment-related changes were observed in organ weights or in the histopathological examination of organs and tissues. The study report authors established a NOAEL of 100 mg/kg bw/day. Due to the ophthalmological and haematological findings at this dose level, the SCCNFP set the NOAEL to 3 mg/kg bw/day. Ref.: 12 Comment The SCCNFP remarked that according to Ref. 15 (Ref. 5 subm. I), a 2% solution of Tetrabromophenol Blue has not been classified as eye irritating and no corneal opacity was observed at this concentration. However, for the highest dose in this 90-day study, 100 mg per kg bw was administered in 5 ml volume per kg, which corresponds to a 2% solution and the observed ophthalmological effects were attributed to direct eye contact. Reassessment by the SCCS In 2004, only a draft stud","page":23,"pdf":"sccs_o_197.pdf","row_type":"noael_study","study_id":"sccs_o_197_noael_002"}
SCCS Opinion NOAEL =3 mg/kg bw/d rat oral 90-day dermal absorption {"citation":"(ref. 21)","dose":"-3-yliden)bis- 2,6-dibromophenol (C183) ___________________________________________________________________________________________ 34 CALCULATION OF THE MARGIN OF SAFETY (non-oxidative conditions) (In formulation, on head concentration 0.2%) Absorption through the skin A = 0.07 µg/cm² Skin Area surface SAS = 580 cm2 Dermal absorption per treatm...","effect":"-3-yliden)bis- 2,6-dibromophenol (C183) ___________________________________________________________________________________________ 34 CALCULATION OF THE MARGIN OF SAFETY (non-oxidative conditions) (In formulation, on head concentration 0.2%) Absorption through the skin A = 0.07 µg/cm² Skin Area surface SAS = 580 cm2 Dermal absorption per treatment SAS x A x 0.001 = 0.0406 mg Typical body weight of human = 60 kg Systemic exposure dose (SED) SAS x A x 0.001/… = 0.00068 mg/kg bw No observed adverse effect level NOAEL = 3 mg/kg bw/d (90-day, oral, rat) Bioavailability 30%* = 0.9 mg/kg bw/d Margin of Safety adjusted NOAEL/SED = 1300 * based on the toxicokinetic study (ref. 21). CALCULATION OF THE MARGIN OF SAFETY (oxidative conditions) (In formulation, on head concentration 0.2%) Absorption through the skin A = 0.04 µg/cm² Skin Area surface SAS = 580 cm2 Dermal absorption per treatment SAS x A x 0.001 = 0.0232 mg Typical body weight of human = 60 kg Systemic exposure dose (SED) SAS x A x 0.001/… = 0.00039 mg/kg bw No obse","page":34,"pdf":"sccs_o_197.pdf","row_type":"noael_study","study_id":"sccs_o_197_noael_013"}
SCCS Opinion NOAEL =5 mg/kg bw/day rat oral - NOAEL study {"citation":"Ref.: 17 Taken from SCCS/1426/11 Guideline: OECD no","dose":"Even in the medium dose one foetus with persistent truncus arteriosus was found.","effect":"SCCS/1573/16 Opinion on hair dye Tetrabromophenol Blue, 4,4’-(4,5,6,7-tetrabromo-1,1-dioxido-3H-2,1-benzoxathiol-3-yliden)bis- 2,6-dibromophenol (C183) ___________________________________________________________________________________________ 29 attributed to treatment. Even in the medium dose one foetus with persistent truncus arteriosus was found. Conclusion The NOAEL of maternal toxicity was 50 mg/kg bw/day, the NOAEL of teratogenicity was 5 mg/kg bw/day. For embryotoxicity, a NOAEL cannot be established. Ref.: 17 Taken from SCCS/1426/11 Guideline: OECD no. 414 (2001) Species/strain: Rat, strain Wistar rats HanBrl: WIST, outbred (SPF) Group size: 22 mated females per dose group Test item: Tetrabromophenol Blue Batch: TBFB3/02/30 Purity: 98.8 area % (at 615 nm, HPLC) Dose levels: 0, 3, 30 and 300 mg/kg bw/day Vehicle: 5% w/w polyglycol 600, 4% w/w Plantaren 2000 UP (50% aqueous decyl glucoside), 90.5% milli-U water Route: oral, gavage GLP: in compliance Study date 3 January – 20 July 2005 E","page":29,"pdf":"sccs_o_197.pdf","row_type":"noael_study","study_id":"sccs_o_197_noael_009"}
SCCS Opinion NOAEL =5 mg/kg bw/day rat oral - NOAEL study {"citation":"Ref.: 17 Taken from SCCS/1426/11 Guideline: OECD no","dose":"Even in the medium dose one foetus with persistent truncus arteriosus was found.","effect":"SCCS/1573/16 Opinion on hair dye Tetrabromophenol Blue, 4,4’-(4,5,6,7-tetrabromo-1,1-dioxido-3H-2,1-benzoxathiol-3-yliden)bis- 2,6-dibromophenol (C183) ___________________________________________________________________________________________ 29 attributed to treatment. Even in the medium dose one foetus with persistent truncus arteriosus was found. Conclusion The NOAEL of maternal toxicity was 50 mg/kg bw/day, the NOAEL of teratogenicity was 5 mg/kg bw/day. For embryotoxicity, a NOAEL cannot be established. Ref.: 17 Taken from SCCS/1426/11 Guideline: OECD no. 414 (2001) Species/strain: Rat, strain Wistar rats HanBrl: WIST, outbred (SPF) Group size: 22 mated females per dose group Test item: Tetrabromophenol Blue Batch: TBFB3/02/30 Purity: 98.8 area % (at 615 nm, HPLC) Dose levels: 0, 3, 30 and 300 mg/kg bw/day Vehicle: 5% w/w polyglycol 600, 4% w/w Plantaren 2000 UP (50% aqueous decyl glucoside), 90.5% milli-U water Route: oral, gavage GLP: in compliance Study date 3 January – 20 July 2005 E","page":29,"pdf":"sccs_o_197.pdf","row_type":"noael_study","study_id":"sccs_o_197_noael_009"}
SCCS Opinion NOAEL =5 mg/kg bw/day rat oral - NOAEL study {"citation":"Ref.: 17 Taken from SCCS/1426/11 Guideline: OECD no","dose":"Even in the medium dose one foetus with persistent truncus arteriosus was found.","effect":"SCCS/1573/16 Opinion on hair dye Tetrabromophenol Blue, 4,4’-(4,5,6,7-tetrabromo-1,1-dioxido-3H-2,1-benzoxathiol-3-yliden)bis- 2,6-dibromophenol (C183) ___________________________________________________________________________________________ 29 attributed to treatment. Even in the medium dose one foetus with persistent truncus arteriosus was found. Conclusion The NOAEL of maternal toxicity was 50 mg/kg bw/day, the NOAEL of teratogenicity was 5 mg/kg bw/day. For embryotoxicity, a NOAEL cannot be established. Ref.: 17 Taken from SCCS/1426/11 Guideline: OECD no. 414 (2001) Species/strain: Rat, strain Wistar rats HanBrl: WIST, outbred (SPF) Group size: 22 mated females per dose group Test item: Tetrabromophenol Blue Batch: TBFB3/02/30 Purity: 98.8 area % (at 615 nm, HPLC) Dose levels: 0, 3, 30 and 300 mg/kg bw/day Vehicle: 5% w/w polyglycol 600, 4% w/w Plantaren 2000 UP (50% aqueous decyl glucoside), 90.5% milli-U water Route: oral, gavage GLP: in compliance Study date 3 January – 20 July 2005 E","page":29,"pdf":"sccs_o_197.pdf","row_type":"noael_study","study_id":"sccs_o_197_noael_009"}
SCCS Opinion NOAEL =5 mg/kg bw/day rat oral - NOAEL study {"citation":"Ref.: 17 Taken from SCCS/1426/11 Guideline: OECD no","dose":"Even in the medium dose one foetus with persistent truncus arteriosus was found.","effect":"SCCS/1573/16 Opinion on hair dye Tetrabromophenol Blue, 4,4’-(4,5,6,7-tetrabromo-1,1-dioxido-3H-2,1-benzoxathiol-3-yliden)bis- 2,6-dibromophenol (C183) ___________________________________________________________________________________________ 29 attributed to treatment. Even in the medium dose one foetus with persistent truncus arteriosus was found. Conclusion The NOAEL of maternal toxicity was 50 mg/kg bw/day, the NOAEL of teratogenicity was 5 mg/kg bw/day. For embryotoxicity, a NOAEL cannot be established. Ref.: 17 Taken from SCCS/1426/11 Guideline: OECD no. 414 (2001) Species/strain: Rat, strain Wistar rats HanBrl: WIST, outbred (SPF) Group size: 22 mated females per dose group Test item: Tetrabromophenol Blue Batch: TBFB3/02/30 Purity: 98.8 area % (at 615 nm, HPLC) Dose levels: 0, 3, 30 and 300 mg/kg bw/day Vehicle: 5% w/w polyglycol 600, 4% w/w Plantaren 2000 UP (50% aqueous decyl glucoside), 90.5% milli-U water Route: oral, gavage GLP: in compliance Study date 3 January – 20 July 2005 E","page":29,"pdf":"sccs_o_197.pdf","row_type":"noael_study","study_id":"sccs_o_197_noael_009"}
SCCS Opinion NOAEL =30 mg/kg bw/ day rat - - NOAEL study {"citation":"Ref: 18 3","dose":"incidences of left-sided umbilical arteries and cranially elongated thymuses at the high dose and anophthalmia in the mid-dose group.","effect":"incidences of left-sided umbilical arteries and cranially elongated thymuses at the high dose and anophthalmia in the mid-dose group. There was an increased incidence of fused zygomatic arches at the high dose (21 in 12 litters) when compared with the control group (12 in 9 litters). A statistically significant increase in supernumerary rudimentary ribs was observed in the mid and high doses. No changes were noted in the foetuses of the low dose group (3 mg/kg bw). Conclusion Based on these results, the maternal NOAEL was considered to be 30 mg/kg bw/ day. A NOAEL for embryo-foetal effects was derived at 3 mg/kg bw/day. Ref: 18 3.3.9 Toxicokinetics 3.3.9.1 Toxicokinetics in laboratory animals Taken from SCCS/1426/11 Guideline: OECD 417 (1984) and OECD 427 (2004) Species/strain: Rat, Wistar CRL: WI BR (outbreed) (SPF) Group size: Females, mass balance groups (groups 1,2,3,4) 4 per dose; toxicokinetics groups (groups 5, 6, 7, 8) 6 per dose Test substances: Tetrabromophenol Blue-(Phenol-UL-14C) Batch: 064K9418 non-labelled T","page":30,"pdf":"sccs_o_197.pdf","row_type":"noael_study","study_id":"sccs_o_197_noael_010"}
SCCS Opinion NOAEL =30 mg/kg bw/ day rat - - NOAEL study {"citation":"Ref: 18 3","dose":"incidences of left-sided umbilical arteries and cranially elongated thymuses at the high dose and anophthalmia in the mid-dose group.","effect":"incidences of left-sided umbilical arteries and cranially elongated thymuses at the high dose and anophthalmia in the mid-dose group. There was an increased incidence of fused zygomatic arches at the high dose (21 in 12 litters) when compared with the control group (12 in 9 litters). A statistically significant increase in supernumerary rudimentary ribs was observed in the mid and high doses. No changes were noted in the foetuses of the low dose group (3 mg/kg bw). Conclusion Based on these results, the maternal NOAEL was considered to be 30 mg/kg bw/ day. A NOAEL for embryo-foetal effects was derived at 3 mg/kg bw/day. Ref: 18 3.3.9 Toxicokinetics 3.3.9.1 Toxicokinetics in laboratory animals Taken from SCCS/1426/11 Guideline: OECD 417 (1984) and OECD 427 (2004) Species/strain: Rat, Wistar CRL: WI BR (outbreed) (SPF) Group size: Females, mass balance groups (groups 1,2,3,4) 4 per dose; toxicokinetics groups (groups 5, 6, 7, 8) 6 per dose Test substances: Tetrabromophenol Blue-(Phenol-UL-14C) Batch: 064K9418 non-labelled T","page":30,"pdf":"sccs_o_197.pdf","row_type":"noael_study","study_id":"sccs_o_197_noael_010"}
SCCS Opinion NOAEL =30 mg/kg bw/ day rat - - NOAEL study {"citation":"Ref: 18 3","dose":"incidences of left-sided umbilical arteries and cranially elongated thymuses at the high dose and anophthalmia in the mid-dose group.","effect":"incidences of left-sided umbilical arteries and cranially elongated thymuses at the high dose and anophthalmia in the mid-dose group. There was an increased incidence of fused zygomatic arches at the high dose (21 in 12 litters) when compared with the control group (12 in 9 litters). A statistically significant increase in supernumerary rudimentary ribs was observed in the mid and high doses. No changes were noted in the foetuses of the low dose group (3 mg/kg bw). Conclusion Based on these results, the maternal NOAEL was considered to be 30 mg/kg bw/ day. A NOAEL for embryo-foetal effects was derived at 3 mg/kg bw/day. Ref: 18 3.3.9 Toxicokinetics 3.3.9.1 Toxicokinetics in laboratory animals Taken from SCCS/1426/11 Guideline: OECD 417 (1984) and OECD 427 (2004) Species/strain: Rat, Wistar CRL: WI BR (outbreed) (SPF) Group size: Females, mass balance groups (groups 1,2,3,4) 4 per dose; toxicokinetics groups (groups 5, 6, 7, 8) 6 per dose Test substances: Tetrabromophenol Blue-(Phenol-UL-14C) Batch: 064K9418 non-labelled T","page":30,"pdf":"sccs_o_197.pdf","row_type":"noael_study","study_id":"sccs_o_197_noael_010"}
SCCS Opinion NOAEL =30 mg/kg bw/ day rat - - NOAEL study {"citation":"Ref: 18 3","dose":"incidences of left-sided umbilical arteries and cranially elongated thymuses at the high dose and anophthalmia in the mid-dose group.","effect":"incidences of left-sided umbilical arteries and cranially elongated thymuses at the high dose and anophthalmia in the mid-dose group. There was an increased incidence of fused zygomatic arches at the high dose (21 in 12 litters) when compared with the control group (12 in 9 litters). A statistically significant increase in supernumerary rudimentary ribs was observed in the mid and high doses. No changes were noted in the foetuses of the low dose group (3 mg/kg bw). Conclusion Based on these results, the maternal NOAEL was considered to be 30 mg/kg bw/ day. A NOAEL for embryo-foetal effects was derived at 3 mg/kg bw/day. Ref: 18 3.3.9 Toxicokinetics 3.3.9.1 Toxicokinetics in laboratory animals Taken from SCCS/1426/11 Guideline: OECD 417 (1984) and OECD 427 (2004) Species/strain: Rat, Wistar CRL: WI BR (outbreed) (SPF) Group size: Females, mass balance groups (groups 1,2,3,4) 4 per dose; toxicokinetics groups (groups 5, 6, 7, 8) 6 per dose Test substances: Tetrabromophenol Blue-(Phenol-UL-14C) Batch: 064K9418 non-labelled T","page":30,"pdf":"sccs_o_197.pdf","row_type":"noael_study","study_id":"sccs_o_197_noael_010"}
SCCS Opinion NOAEL =50 mg/kg bw/day rat - - NOAEL study {"citation":"Ref.: 17 Taken from SCCS/1426/11 Guideline: OECD no","dose":"Even in the medium dose one foetus with persistent truncus arteriosus was found.","effect":"SCCS/1573/16 Opinion on hair dye Tetrabromophenol Blue, 4,4’-(4,5,6,7-tetrabromo-1,1-dioxido-3H-2,1-benzoxathiol-3-yliden)bis- 2,6-dibromophenol (C183) ___________________________________________________________________________________________ 29 attributed to treatment. Even in the medium dose one foetus with persistent truncus arteriosus was found. Conclusion The NOAEL of maternal toxicity was 50 mg/kg bw/day, the NOAEL of teratogenicity was 5 mg/kg bw/day. For embryotoxicity, a NOAEL cannot be established. Ref.: 17 Taken from SCCS/1426/11 Guideline: OECD no. 414 (2001) Species/strain: Rat, strain Wistar rats HanBrl: WIST, outbred (SPF) Group size: 22 mated females per dose group Test item: Tetrabromophenol Blue Batch: TBFB3/02/30 Purity: 98.8 area % (at 615 nm, HPLC) Dose levels: 0, 3, 30 and 300 mg/kg bw/day Vehicle: 5% w/w polyglycol 600, 4% w/w Plantaren 2000 UP (50% aqueo","page":29,"pdf":"sccs_o_197.pdf","row_type":"noael_study","study_id":"sccs_o_197_noael_008"}
SCCS Opinion NOAEL =50 mg/kg bw/day rat - - NOAEL study {"citation":"Ref.: 17 Taken from SCCS/1426/11 Guideline: OECD no","dose":"Even in the medium dose one foetus with persistent truncus arteriosus was found.","effect":"SCCS/1573/16 Opinion on hair dye Tetrabromophenol Blue, 4,4’-(4,5,6,7-tetrabromo-1,1-dioxido-3H-2,1-benzoxathiol-3-yliden)bis- 2,6-dibromophenol (C183) ___________________________________________________________________________________________ 29 attributed to treatment. Even in the medium dose one foetus with persistent truncus arteriosus was found. Conclusion The NOAEL of maternal toxicity was 50 mg/kg bw/day, the NOAEL of teratogenicity was 5 mg/kg bw/day. For embryotoxicity, a NOAEL cannot be established. Ref.: 17 Taken from SCCS/1426/11 Guideline: OECD no. 414 (2001) Species/strain: Rat, strain Wistar rats HanBrl: WIST, outbred (SPF) Group size: 22 mated females per dose group Test item: Tetrabromophenol Blue Batch: TBFB3/02/30 Purity: 98.8 area % (at 615 nm, HPLC) Dose levels: 0, 3, 30 and 300 mg/kg bw/day Vehicle: 5% w/w polyglycol 600, 4% w/w Plantaren 2000 UP (50% aqueo","page":29,"pdf":"sccs_o_197.pdf","row_type":"noael_study","study_id":"sccs_o_197_noael_008"}
SCCS Opinion NOAEL =50 mg/kg bw/day rat - - NOAEL study {"citation":"Ref.: 17 Taken from SCCS/1426/11 Guideline: OECD no","dose":"Even in the medium dose one foetus with persistent truncus arteriosus was found.","effect":"SCCS/1573/16 Opinion on hair dye Tetrabromophenol Blue, 4,4’-(4,5,6,7-tetrabromo-1,1-dioxido-3H-2,1-benzoxathiol-3-yliden)bis- 2,6-dibromophenol (C183) ___________________________________________________________________________________________ 29 attributed to treatment. Even in the medium dose one foetus with persistent truncus arteriosus was found. Conclusion The NOAEL of maternal toxicity was 50 mg/kg bw/day, the NOAEL of teratogenicity was 5 mg/kg bw/day. For embryotoxicity, a NOAEL cannot be established. Ref.: 17 Taken from SCCS/1426/11 Guideline: OECD no. 414 (2001) Species/strain: Rat, strain Wistar rats HanBrl: WIST, outbred (SPF) Group size: 22 mated females per dose group Test item: Tetrabromophenol Blue Batch: TBFB3/02/30 Purity: 98.8 area % (at 615 nm, HPLC) Dose levels: 0, 3, 30 and 300 mg/kg bw/day Vehicle: 5% w/w polyglycol 600, 4% w/w Plantaren 2000 UP (50% aqueo","page":29,"pdf":"sccs_o_197.pdf","row_type":"noael_study","study_id":"sccs_o_197_noael_008"}
SCCS Opinion NOAEL =50 mg/kg bw/day rat - - NOAEL study {"citation":"Ref.: 17 Taken from SCCS/1426/11 Guideline: OECD no","dose":"Even in the medium dose one foetus with persistent truncus arteriosus was found.","effect":"SCCS/1573/16 Opinion on hair dye Tetrabromophenol Blue, 4,4’-(4,5,6,7-tetrabromo-1,1-dioxido-3H-2,1-benzoxathiol-3-yliden)bis- 2,6-dibromophenol (C183) ___________________________________________________________________________________________ 29 attributed to treatment. Even in the medium dose one foetus with persistent truncus arteriosus was found. Conclusion The NOAEL of maternal toxicity was 50 mg/kg bw/day, the NOAEL of teratogenicity was 5 mg/kg bw/day. For embryotoxicity, a NOAEL cannot be established. Ref.: 17 Taken from SCCS/1426/11 Guideline: OECD no. 414 (2001) Species/strain: Rat, strain Wistar rats HanBrl: WIST, outbred (SPF) Group size: 22 mated females per dose group Test item: Tetrabromophenol Blue Batch: TBFB3/02/30 Purity: 98.8 area % (at 615 nm, HPLC) Dose levels: 0, 3, 30 and 300 mg/kg bw/day Vehicle: 5% w/w polyglycol 600, 4% w/w Plantaren 2000 UP (50% aqueo","page":29,"pdf":"sccs_o_197.pdf","row_type":"noael_study","study_id":"sccs_o_197_noael_008"}
SCCS Opinion NOAEL =100 mg/kg bw/day - - 90-day NOAEL study {"citation":"Ref.: 12 Comment The SCCNFP remarked that according to Ref","dose":"ytes counts observed in males which were statistically significant at 10 and 100 mg/kg bw/day point to a haematotoxic potential of the test substance.","effect":"ytes counts observed in males which were statistically significant at 10 and 100 mg/kg bw/day point to a haematotoxic potential of the test substance. Following the dose of 100 mg/kg bw/day changes in urea (males) and cholesterol (females) values were found. Discolouration of the gastro-intestinal tract was observed and related to the staining properties. No treatment-related changes were observed in organ weights or in the histopathological examination of organs and tissues. The study report authors established a NOAEL of 100 mg/kg bw/day. Due to the ophthalmological and haematological findings at this dose level, the SCCNFP set the NOAEL to 3 mg/kg bw/day. Ref.: 12 Comment The SCCNFP remarked that according to Ref. 15 (Ref. 5 subm. I), a 2% solution of Tetrabromophenol Blue has not been classified as eye irritating and no corneal opacity was observed at this concentration. However, for the highest dose in this 90-day study, 100 mg per kg bw was administered in 5 ml volume per kg, which corresponds to a 2% solution and the obs","page":23,"pdf":"sccs_o_197.pdf","row_type":"noael_study","study_id":"sccs_o_197_noael_001"}
SCCS Opinion NOAEL =100 mg/kg bw/day - - 90-day NOAEL study {"citation":"Ref.: 12 Comment The SCCNFP remarked that according to Ref","dose":"ytes counts observed in males which were statistically significant at 10 and 100 mg/kg bw/day point to a haematotoxic potential of the test substance.","effect":"ytes counts observed in males which were statistically significant at 10 and 100 mg/kg bw/day point to a haematotoxic potential of the test substance. Following the dose of 100 mg/kg bw/day changes in urea (males) and cholesterol (females) values were found. Discolouration of the gastro-intestinal tract was observed and related to the staining properties. No treatment-related changes were observed in organ weights or in the histopathological examination of organs and tissues. The study report authors established a NOAEL of 100 mg/kg bw/day. Due to the ophthalmological and haematological findings at this dose level, the SCCNFP set the NOAEL to 3 mg/kg bw/day. Ref.: 12 Comment The SCCNFP remarked that according to Ref. 15 (Ref. 5 subm. I), a 2% solution of Tetrabromophenol Blue has not been classified as eye irritating and no corneal opacity was observed at this concentration. However, for the highest dose in this 90-day study, 100 mg per kg bw was administered in 5 ml volume per kg, which corresponds to a 2% solution and the obs","page":23,"pdf":"sccs_o_197.pdf","row_type":"noael_study","study_id":"sccs_o_197_noael_001"}
SCCS Opinion NOAEL =100 mg/kg bw/day - - 90-day NOAEL study {"citation":"Ref.: 12 Comment The SCCNFP remarked that according to Ref","dose":"ytes counts observed in males which were statistically significant at 10 and 100 mg/kg bw/day point to a haematotoxic potential of the test substance.","effect":"ytes counts observed in males which were statistically significant at 10 and 100 mg/kg bw/day point to a haematotoxic potential of the test substance. Following the dose of 100 mg/kg bw/day changes in urea (males) and cholesterol (females) values were found. Discolouration of the gastro-intestinal tract was observed and related to the staining properties. No treatment-related changes were observed in organ weights or in the histopathological examination of organs and tissues. The study report authors established a NOAEL of 100 mg/kg bw/day. Due to the ophthalmological and haematological findings at this dose level, the SCCNFP set the NOAEL to 3 mg/kg bw/day. Ref.: 12 Comment The SCCNFP remarked that according to Ref. 15 (Ref. 5 subm. I), a 2% solution of Tetrabromophenol Blue has not been classified as eye irritating and no corneal opacity was observed at this concentration. However, for the highest dose in this 90-day study, 100 mg per kg bw was administered in 5 ml volume per kg, which corresponds to a 2% solution and the obs","page":23,"pdf":"sccs_o_197.pdf","row_type":"noael_study","study_id":"sccs_o_197_noael_001"}
SCCS Opinion NOAEL =100 mg/kg bw/day - - 90-day NOAEL study {"citation":"Ref.: 12 Comment The SCCNFP remarked that according to Ref","dose":"ytes counts observed in males which were statistically significant at 10 and 100 mg/kg bw/day point to a haematotoxic potential of the test substance.","effect":"ytes counts observed in males which were statistically significant at 10 and 100 mg/kg bw/day point to a haematotoxic potential of the test substance. Following the dose of 100 mg/kg bw/day changes in urea (males) and cholesterol (females) values were found. Discolouration of the gastro-intestinal tract was observed and related to the staining properties. No treatment-related changes were observed in organ weights or in the histopathological examination of organs and tissues. The study report authors established a NOAEL of 100 mg/kg bw/day. Due to the ophthalmological and haematological findings at this dose level, the SCCNFP set the NOAEL to 3 mg/kg bw/day. Ref.: 12 Comment The SCCNFP remarked that according to Ref. 15 (Ref. 5 subm. I), a 2% solution of Tetrabromophenol Blue has not been classified as eye irritating and no corneal opacity was observed at this concentration. However, for the highest dose in this 90-day study, 100 mg per kg bw was administered in 5 ml volume per kg, which corresponds to a 2% solution and the obs","page":23,"pdf":"sccs_o_197.pdf","row_type":"noael_study","study_id":"sccs_o_197_noael_001"}
Regulatory source 65 endpoints
Source Endpoint Type Value Unit Species Route Duration Study Type Reference
Regulatory source - 5 mg/kg bw/day - - - - SOURCE_SUBDIR=out283_en; REPORT_TITLE=OPINION OF THE SCIENTIFIC COMMITTEE ON COSMETIC PRODUCTS AND NON-FOOD PRODUCTS INTENDED FOR CONSUMERS CONCERNING TETRABROMOPHENOL BLUE COLIPA n° : /; OPINION_NUMBER=SCCNFP/0794/04; COMMITTEE=SCCNFP; REPORT_DATE=25 May 2004; VALUE_TEXT=5; DOSE=Incidental cases of malformations were seen in all dose groups including controls (e.g. polydactyly, exencephaly, spina bifida, abnormal shape of limb bones) but the effects were not dose-related.; EFFECT=bw/day a generalised reduction in ossification was seen. Incidental cases of malformations were seen in all dose groups including controls (e.g. polydactyly, exencephaly, spina bifida, abnormal shape of limb bones) but the effects were not dose-related. In the high dose group 18 of 166 analysed foetuses showed changes of the major arteries which should be attributed to treatment. Even in the medium dose one foetus with persistent truncus arteriosus was found. The NOAEL of maternal toxicity was 50 mg/kg bw/day, the NOAEL of teratogenicity was 5 mg/kg bw/day. For embryotoxicity, a NOAEL cannot be established. Ref.: 7; CITATION_NUMBERS=[]; DETAILS_JSON={"cas_number":"4430-25-5","citation":"","dose":"Incidental cases of malformations were seen in all dose groups including controls (e.g. polydactyly, exencephaly, spina bifida, abnormal shape of limb bones) but the effects were not dose-related.","duration":"","effect":"bw/day a generalised reduction in ossification was seen. Incidental cases of malformations were seen in all dose groups including controls (e.g. polydactyly, exencephaly, spina bifida, abnormal shape of limb bones) but the effects were not dose-related. In the high dose group 18 of 166 analysed foetuses showed changes of the major arteries which should be attributed to treatment. Even in the medium dose one foetus with persistent truncus arteriosus was found. The NOAEL of maternal toxicity was 50 mg/kg bw/day, the NOAEL of teratogenicity was 5 mg/kg bw/day. For embryotoxicity, a NOAEL cannot be established. Ref.: 7","endpoint":"","ingredient":"s below correspond to the octabromo-derivative only, while the","loael_value":"","noael_unit":"mg/kg bw/day","noael_value":"5","page":12,"route":"","species":"","study_id":"out283_en_noael_005"}
Regulatory source - 5 mg/kg bw/day - - - - SOURCE_SUBDIR=out283_en; REPORT_TITLE=OPINION OF THE SCIENTIFIC COMMITTEE ON COSMETIC PRODUCTS AND NON-FOOD PRODUCTS INTENDED FOR CONSUMERS CONCERNING TETRABROMOPHENOL BLUE COLIPA n° : /; OPINION_NUMBER=SCCNFP/0794/04; COMMITTEE=SCCNFP; REPORT_DATE=25 May 2004; VALUE_TEXT=5; DOSE=l cases of malformations were seen in all dose groups including controls (e.g. polydactyly, exencephaly, spina bifida, abnormal shape of limb bones) but the effects were not dose-related.; EFFECT=l cases of malformations were seen in all dose groups including controls (e.g. polydactyly, exencephaly, spina bifida, abnormal shape of limb bones) but the effects were not dose-related. In the high dose group 18 of 166 analysed foetuses showed changes of the major arteries which should be attributed to treatment. Even in the medium dose one foetus with persistent truncus arteriosus was found. The NOAEL of maternal toxicity was 50 mg/kg bw/day, the NOAEL of teratogenicity was 5 mg/kg bw/day. For embryotoxicity, a NOAEL cannot be established. Ref.: 7; CITATION_NUMBERS=[]; DETAILS_JSON={"cas_number":"4430-25-5","citation":"","dose":"l cases of malformations were seen in all dose groups including controls (e.g. polydactyly, exencephaly, spina bifida, abnormal shape of limb bones) but the effects were not dose-related.","duration":"","effect":"l cases of malformations were seen in all dose groups including controls (e.g. polydactyly, exencephaly, spina bifida, abnormal shape of limb bones) but the effects were not dose-related. In the high dose group 18 of 166 analysed foetuses showed changes of the major arteries which should be attributed to treatment. Even in the medium dose one foetus with persistent truncus arteriosus was found. The NOAEL of maternal toxicity was 50 mg/kg bw/day, the NOAEL of teratogenicity was 5 mg/kg bw/day. For embryotoxicity, a NOAEL cannot be established. Ref.: 7","endpoint":"","ingredient":"s below correspond to the octabromo-derivative only, while the","loael_value":"","noael_unit":"mg/kg bw/day","noael_value":"5","page":12,"route":"","species":"","study_id":"out283_en_noael_006"}
Regulatory source - 50 mg/kg bw/day - - - - SOURCE_SUBDIR=out283_en; REPORT_TITLE=OPINION OF THE SCIENTIFIC COMMITTEE ON COSMETIC PRODUCTS AND NON-FOOD PRODUCTS INTENDED FOR CONSUMERS CONCERNING TETRABROMOPHENOL BLUE COLIPA n° : /; OPINION_NUMBER=SCCNFP/0794/04; COMMITTEE=SCCNFP; REPORT_DATE=25 May 2004; VALUE_TEXT=50; DOSE=half of the 50 mg/kg dose.; EFFECT=half of the 50 mg/kg dose. At the low dose 5 mg/kg bw/day a generalised reduction in ossification was seen. Incidental cases of malformations were seen in all dose groups including controls (e.g. polydactyly, exencephaly, spina bifida, abnormal shape of limb bones) but the effects were not dose-related. In the high dose group 18 of 166 analysed foetuses showed changes of the major arteries which should be attributed to treatment. Even in the medium dose one foetus with persistent truncus arteriosus was found. The NOAEL of maternal toxicity was 50 mg/kg bw/day, the NOAEL of teratogenicity was 5 mg/kg bw/day. For embryotoxicity, a NOAEL cannot be established. Ref.: 7; CITATION_NUMBERS=[]; DETAILS_JSON={"cas_number":"4430-25-5","citation":"","dose":"half of the 50 mg/kg dose.","duration":"","effect":"half of the 50 mg/kg dose. At the low dose 5 mg/kg bw/day a generalised reduction in ossification was seen. Incidental cases of malformations were seen in all dose groups including controls (e.g. polydactyly, exencephaly, spina bifida, abnormal shape of limb bones) but the effects were not dose-related. In the high dose group 18 of 166 analysed foetuses showed changes of the major arteries which should be attributed to treatment. Even in the medium dose one foetus with persistent truncus arteriosus was found. The NOAEL of maternal toxicity was 50 mg/kg bw/day, the NOAEL of teratogenicity was 5 mg/kg bw/day. For embryotoxicity, a NOAEL cannot be established. Ref.: 7","endpoint":"","ingredient":"s below correspond to the octabromo-derivative only, while the","loael_value":"","noael_unit":"mg/kg bw/day","noael_value":"50","page":12,"route":"","species":"","study_id":"out283_en_noael_004"}
Regulatory source repeated dose toxicity 0.2 % - - sub-chronic repeated dose toxicity SOURCE_SUBDIR=out283_en; REPORT_TITLE=OPINION OF THE SCIENTIFIC COMMITTEE ON COSMETIC PRODUCTS AND NON-FOOD PRODUCTS INTENDED FOR CONSUMERS CONCERNING TETRABROMOPHENOL BLUE COLIPA n° : /; OPINION_NUMBER=SCCNFP/0794/04; COMMITTEE=SCCNFP; REPORT_DATE=25 May 2004; VALUE_TEXT=0.2; DOSE=evaluate possible substance-related changes in absolute and relative body weights (repeated dose study).; EFFECT=evaluate possible substance-related changes in absolute and relative body weights (repeated dose study). Blue discolouration of the faeces and other body parts was seen in the dose groups 10 and 100 mg/kg bw/day (repeated dose) and in all doses (sub-chronic). No relevant substance-related clinical findings were noted. The NOAEL in the subchronic toxicity study was set at 3 mg/kg bw/day. The NOAEL for maternal toxicity was set at 50 mg/kg bw/day, the NOAEL for teratogenicity was 5 mg/kg bw/day, for embryotoxicity a NOAEL could not be established. Tetrabromophenol Blue is not a skin irritant. Although the neat substance poses a risk of serious damage to the eyes, no effect was noted at the proposed use concentration of 0.2%. Tetrabromophenol Blue is not a sensitiser when used as intended. The percutaneous absorption study is inadequate. Tetrabromophenol has been tested for the induction of gene mutations in bacterial and in mammalian cells. The test item is non mutagenic on bacterial cells. The in vitro mammalian cell test is in; CITATION_NUMBERS=[]; DETAILS_JSON={"cas_number":"4430-25-5","citation":"","dose":"evaluate possible substance-related changes in absolute and relative body weights (repeated dose study).","duration":"sub-chronic","effect":"evaluate possible substance-related changes in absolute and relative body weights (repeated dose study). Blue discolouration of the faeces and other body parts was seen in the dose groups 10 and 100 mg/kg bw/day (repeated dose) and in all doses (sub-chronic). No relevant substance-related clinical findings were noted. The NOAEL in the subchronic toxicity study was set at 3 mg/kg bw/day. The NOAEL for maternal toxicity was set at 50 mg/kg bw/day, the NOAEL for teratogenicity was 5 mg/kg bw/day, for embryotoxicity a NOAEL could not be established. Tetrabromophenol Blue is not a skin irritant. Although the neat substance poses a risk of serious damage to the eyes, no effect was noted at the proposed use concentration of 0.2%. Tetrabromophenol Blue is not a sensitiser when used as intended. The percutaneous absorption study is inadequate. Tetrabromophenol has been tested for the induction of gene mutations in bacterial and in mammalian cells. The test item is non mutagenic on bacterial cells. The in vitro mammalian cell test is in","endpoint":"repeated dose toxicity","ingredient":"s below correspond to the octabromo-derivative only, while the","loael_value":"","noael_unit":"%","noael_value":"0.2","page":16,"route":"","species":"","study_id":"out283_en_noael_010"}
Regulatory source repeated dose toxicity 3 mg/kg bw/day rat oral Subchronic repeated dose toxicity SOURCE_SUBDIR=out283_en; REPORT_TITLE=OPINION OF THE SCIENTIFIC COMMITTEE ON COSMETIC PRODUCTS AND NON-FOOD PRODUCTS INTENDED FOR CONSUMERS CONCERNING TETRABROMOPHENOL BLUE COLIPA n° : /; OPINION_NUMBER=SCCNFP/0794/04; COMMITTEE=SCCNFP; REPORT_DATE=25 May 2004; VALUE_TEXT=3; DOSE=SCCNFP/0794/04 Evaluation and opinion on Tetrabromophenol Blue _____________________________________________________________________________________________ 8 The authors established a NOAEL of 3 mg/kg bw/day.; EFFECT=SCCNFP/0794/04 Evaluation and opinion on Tetrabromophenol Blue _____________________________________________________________________________________________ 8 The authors established a NOAEL of 3 mg/kg bw/day. Ref.: 2b 2.3.5 Repeated dose dermal toxicity No data 2.3.6. Repeated dose inhalation toxicity No data 2.3.7. Subchronic oral toxicity Guideline : OECD 408 (1998) Species/strain : SPF-bred Wistar rats Group size : 10 males and 10 females per dose group Test substance : Tetrabromophenol Blue dissolved in water containing 5.3 % polyglycol 600 and 4.2 % of a 50 % aqueous decyl glucoside solution Batch number : TBFB3/02/30 Purity : 96.7-98.8 % Dose levels : 0, 3, 10 and 100 mg; CITATION=Ref.: 2b 2; CITATION_NUMBERS=[2]; REFERENCE=Ref.: 2b 2; DETAILS_JSON={"cas_number":"4430-25-5","citation":"Ref.: 2b 2","dose":"SCCNFP/0794/04 Evaluation and opinion on Tetrabromophenol Blue _____________________________________________________________________________________________ 8 The authors established a NOAEL of 3 mg/kg bw/day.","duration":"Subchronic","effect":"SCCNFP/0794/04 Evaluation and opinion on Tetrabromophenol Blue _____________________________________________________________________________________________ 8 The authors established a NOAEL of 3 mg/kg bw/day. Ref.: 2b 2.3.5 Repeated dose dermal toxicity No data 2.3.6. Repeated dose inhalation toxicity No data 2.3.7. Subchronic oral toxicity Guideline : OECD 408 (1998) Species/strain : SPF-bred Wistar rats Group size : 10 males and 10 females per dose group Test substance : Tetrabromophenol Blue dissolved in water containing 5.3 % polyglycol 600 and 4.2 % of a 50 % aqueous decyl glucoside solution Batch number : TBFB3/02/30 Purity : 96.7-98.8 % Dose levels : 0, 3, 10 and 100 mg","endpoint":"repeated dose toxicity","ingredient":"s below correspond to the octabromo-derivative only, while the","loael_value":"","noael_unit":"mg/kg bw/day","noael_value":"3","page":8,"route":"oral","species":"rat","study_id":"out283_en_noael_001"}
Regulatory source repeated dose toxicity 3 mg/kg bw/day rabbit dermal Sub-chronic repeated dose toxicity SOURCE_SUBDIR=out283_en; REPORT_TITLE=OPINION OF THE SCIENTIFIC COMMITTEE ON COSMETIC PRODUCTS AND NON-FOOD PRODUCTS INTENDED FOR CONSUMERS CONCERNING TETRABROMOPHENOL BLUE COLIPA n° : /; OPINION_NUMBER=SCCNFP/0794/04; COMMITTEE=SCCNFP; REPORT_DATE=25 May 2004; VALUE_TEXT=3; DOSE=SCCNFP/0794/04 Evaluation and opinion on Tetrabromophenol Blue _____________________________________________________________________________________________ 9 NOAEL of 10 mg/kg bw/day.; EFFECT=SCCNFP/0794/04 Evaluation and opinion on Tetrabromophenol Blue _____________________________________________________________________________________________ 9 NOAEL of 10 mg/kg bw/day. Due to the ophthalmological and haematological findings at this dose level, the SCCNFP set the NOAEL to 3 mg/kg bw/day. Comment According to Ref. 5 a 2 % solution of Tetrabromophenol Blue has not be classified as eye irritating. For the highest dose in this study 100 mg per kg bw was administered in 5 ml volume per kg. This may be approximately a 2 % solution. Ref.: 2 2.3.8. Sub-chronic dermal toxicity No data 2.3.9. Sub-chronic inhalation toxicity No data 2.3.10. Chronic toxicity No data 2.4. Irritation & corrosivity 2.4.1. Irritation (skin) Guideline : OECD 404 (1992) Species/strain : Albino Rabbit, N; CITATION=Ref.: 2 2; CITATION_NUMBERS=[2]; REFERENCE=Ref.: 2 2; DETAILS_JSON={"cas_number":"4430-25-5","citation":"Ref.: 2 2","dose":"SCCNFP/0794/04 Evaluation and opinion on Tetrabromophenol Blue _____________________________________________________________________________________________ 9 NOAEL of 10 mg/kg bw/day.","duration":"Sub-chronic","effect":"SCCNFP/0794/04 Evaluation and opinion on Tetrabromophenol Blue _____________________________________________________________________________________________ 9 NOAEL of 10 mg/kg bw/day. Due to the ophthalmological and haematological findings at this dose level, the SCCNFP set the NOAEL to 3 mg/kg bw/day. Comment According to Ref. 5 a 2 % solution of Tetrabromophenol Blue has not be classified as eye irritating. For the highest dose in this study 100 mg per kg bw was administered in 5 ml volume per kg. This may be approximately a 2 % solution. Ref.: 2 2.3.8. Sub-chronic dermal toxicity No data 2.3.9. Sub-chronic inhalation toxicity No data 2.3.10. Chronic toxicity No data 2.4. Irritation & corrosivity 2.4.1. Irritation (skin) Guideline : OECD 404 (1992) Species/strain : Albino Rabbit, N","endpoint":"repeated dose toxicity","ingredient":"s below correspond to the octabromo-derivative only, while the","loael_value":"","noael_unit":"mg/kg bw/day","noael_value":"3","page":9,"route":"dermal","species":"rabbit","study_id":"out283_en_noael_003"}
Regulatory source repeated dose toxicity 3 mg/kg bw/day - - sub-chronic repeated dose toxicity SOURCE_SUBDIR=out283_en; REPORT_TITLE=OPINION OF THE SCIENTIFIC COMMITTEE ON COSMETIC PRODUCTS AND NON-FOOD PRODUCTS INTENDED FOR CONSUMERS CONCERNING TETRABROMOPHENOL BLUE COLIPA n° : /; OPINION_NUMBER=SCCNFP/0794/04; COMMITTEE=SCCNFP; REPORT_DATE=25 May 2004; VALUE_TEXT=3; DOSE=However, no treatment-related mortality occurred in a repeated dose and a sub-chronic toxicity study.; EFFECT=ity was submitted. However, no treatment-related mortality occurred in a repeated dose and a sub-chronic toxicity study. Missing values in male control organ and body weights make it difficult to evaluate possible substance-related changes in absolute and relative body weights (repeated dose study). Blue discolouration of the faeces and other body parts was seen in the dose groups 10 and 100 mg/kg bw/day (repeated dose) and in all doses (sub-chronic). No relevant substance-related clinical findings were noted. The NOAEL in the subchronic toxicity study was set at 3 mg/kg bw/day. The NOAEL for maternal toxicity was set at 50 mg/kg bw/day, the NOAEL for teratogenicity was 5 mg/kg bw/day, for embryotoxicity a NOAEL could not be established. Tetrabromophenol Blue is not a skin irritant. Although the neat substance poses a risk of serious damage to the eyes, no effect was noted at the proposed use concentration of 0.2%. Tetrabromophenol Blue is not a sensitiser when used as intended. The percutaneous absorption study is inadequate.; CITATION_NUMBERS=[]; DETAILS_JSON={"cas_number":"4430-25-5","citation":"","dose":"However, no treatment-related mortality occurred in a repeated dose and a sub-chronic toxicity study.","duration":"sub-chronic","effect":"ity was submitted. However, no treatment-related mortality occurred in a repeated dose and a sub-chronic toxicity study. Missing values in male control organ and body weights make it difficult to evaluate possible substance-related changes in absolute and relative body weights (repeated dose study). Blue discolouration of the faeces and other body parts was seen in the dose groups 10 and 100 mg/kg bw/day (repeated dose) and in all doses (sub-chronic). No relevant substance-related clinical findings were noted. The NOAEL in the subchronic toxicity study was set at 3 mg/kg bw/day. The NOAEL for maternal toxicity was set at 50 mg/kg bw/day, the NOAEL for teratogenicity was 5 mg/kg bw/day, for embryotoxicity a NOAEL could not be established. Tetrabromophenol Blue is not a skin irritant. Although the neat substance poses a risk of serious damage to the eyes, no effect was noted at the proposed use concentration of 0.2%. Tetrabromophenol Blue is not a sensitiser when used as intended. The percutaneous absorption study is inadequate.","endpoint":"repeated dose toxicity","ingredient":"s below correspond to the octabromo-derivative only, while the","loael_value":"","noael_unit":"mg/kg bw/day","noael_value":"3","page":16,"route":"","species":"","study_id":"out283_en_noael_007"}
Regulatory source repeated dose toxicity 5 mg/kg bw/day - - sub-chronic repeated dose toxicity SOURCE_SUBDIR=out283_en; REPORT_TITLE=OPINION OF THE SCIENTIFIC COMMITTEE ON COSMETIC PRODUCTS AND NON-FOOD PRODUCTS INTENDED FOR CONSUMERS CONCERNING TETRABROMOPHENOL BLUE COLIPA n° : /; OPINION_NUMBER=SCCNFP/0794/04; COMMITTEE=SCCNFP; REPORT_DATE=25 May 2004; VALUE_TEXT=5; DOSE=alues in male control organ and body weights make it difficult to evaluate possible substance-related changes in absolute and relative body weights (repeated dose study).; EFFECT=alues in male control organ and body weights make it difficult to evaluate possible substance-related changes in absolute and relative body weights (repeated dose study). Blue discolouration of the faeces and other body parts was seen in the dose groups 10 and 100 mg/kg bw/day (repeated dose) and in all doses (sub-chronic). No relevant substance-related clinical findings were noted. The NOAEL in the subchronic toxicity study was set at 3 mg/kg bw/day. The NOAEL for maternal toxicity was set at 50 mg/kg bw/day, the NOAEL for teratogenicity was 5 mg/kg bw/day, for embryotoxicity a NOAEL could not be established. Tetrabromophenol Blue is not a skin irritant. Although the neat substance poses a risk of serious damage to the eyes, no effect was noted at the proposed use concentration of 0.2%. Tetrabromophenol Blue is not a sensitiser when used as intended. The percutaneous absorption study is inadequate. Tetrabromophenol has been tested for the induction of gene mutations in bacterial and in mammalian cells. The test item is non mu; CITATION_NUMBERS=[]; DETAILS_JSON={"cas_number":"4430-25-5","citation":"","dose":"alues in male control organ and body weights make it difficult to evaluate possible substance-related changes in absolute and relative body weights (repeated dose study).","duration":"sub-chronic","effect":"alues in male control organ and body weights make it difficult to evaluate possible substance-related changes in absolute and relative body weights (repeated dose study). Blue discolouration of the faeces and other body parts was seen in the dose groups 10 and 100 mg/kg bw/day (repeated dose) and in all doses (sub-chronic). No relevant substance-related clinical findings were noted. The NOAEL in the subchronic toxicity study was set at 3 mg/kg bw/day. The NOAEL for maternal toxicity was set at 50 mg/kg bw/day, the NOAEL for teratogenicity was 5 mg/kg bw/day, for embryotoxicity a NOAEL could not be established. Tetrabromophenol Blue is not a skin irritant. Although the neat substance poses a risk of serious damage to the eyes, no effect was noted at the proposed use concentration of 0.2%. Tetrabromophenol Blue is not a sensitiser when used as intended. The percutaneous absorption study is inadequate. Tetrabromophenol has been tested for the induction of gene mutations in bacterial and in mammalian cells. The test item is non mu","endpoint":"repeated dose toxicity","ingredient":"s below correspond to the octabromo-derivative only, while the","loael_value":"","noael_unit":"mg/kg bw/day","noael_value":"5","page":16,"route":"","species":"","study_id":"out283_en_noael_009"}
Regulatory source repeated dose toxicity 10 mg/kg bw/day - dermal Sub-chronic repeated dose toxicity SOURCE_SUBDIR=out283_en; REPORT_TITLE=OPINION OF THE SCIENTIFIC COMMITTEE ON COSMETIC PRODUCTS AND NON-FOOD PRODUCTS INTENDED FOR CONSUMERS CONCERNING TETRABROMOPHENOL BLUE COLIPA n° : /; OPINION_NUMBER=SCCNFP/0794/04; COMMITTEE=SCCNFP; REPORT_DATE=25 May 2004; VALUE_TEXT=10; DOSE=SCCNFP/0794/04 Evaluation and opinion on Tetrabromophenol Blue _____________________________________________________________________________________________ 9 NOAEL of 10 mg/kg bw/day.; EFFECT=SCCNFP/0794/04 Evaluation and opinion on Tetrabromophenol Blue _____________________________________________________________________________________________ 9 NOAEL of 10 mg/kg bw/day. Due to the ophthalmological and haematological findings at this dose level, the SCCNFP set the NOAEL to 3 mg/kg bw/day. Comment According to Ref. 5 a 2 % solution of Tetrabromophenol Blue has not be classified as eye irritating. For the highest dose in this study 100 mg per kg bw was administered in 5 ml volume per kg. This may be approximately a 2 % solution. Ref.: 2 2.3.8. Sub-chronic dermal toxicity No data 2.3.9. Sub-chronic inhalation toxicity No data 2.3.10. Chronic toxicity No dat; CITATION=Ref.: 2 2; CITATION_NUMBERS=[2]; REFERENCE=Ref.: 2 2; DETAILS_JSON={"cas_number":"4430-25-5","citation":"Ref.: 2 2","dose":"SCCNFP/0794/04 Evaluation and opinion on Tetrabromophenol Blue _____________________________________________________________________________________________ 9 NOAEL of 10 mg/kg bw/day.","duration":"Sub-chronic","effect":"SCCNFP/0794/04 Evaluation and opinion on Tetrabromophenol Blue _____________________________________________________________________________________________ 9 NOAEL of 10 mg/kg bw/day. Due to the ophthalmological and haematological findings at this dose level, the SCCNFP set the NOAEL to 3 mg/kg bw/day. Comment According to Ref. 5 a 2 % solution of Tetrabromophenol Blue has not be classified as eye irritating. For the highest dose in this study 100 mg per kg bw was administered in 5 ml volume per kg. This may be approximately a 2 % solution. Ref.: 2 2.3.8. Sub-chronic dermal toxicity No data 2.3.9. Sub-chronic inhalation toxicity No data 2.3.10. Chronic toxicity No dat","endpoint":"repeated dose toxicity","ingredient":"s below correspond to the octabromo-derivative only, while the","loael_value":"","noael_unit":"mg/kg bw/day","noael_value":"10","page":9,"route":"dermal","species":"","study_id":"out283_en_noael_002"}
Regulatory source repeated dose toxicity 50 mg/kg bw/day - - sub-chronic repeated dose toxicity SOURCE_SUBDIR=out283_en; REPORT_TITLE=OPINION OF THE SCIENTIFIC COMMITTEE ON COSMETIC PRODUCTS AND NON-FOOD PRODUCTS INTENDED FOR CONSUMERS CONCERNING TETRABROMOPHENOL BLUE COLIPA n° : /; OPINION_NUMBER=SCCNFP/0794/04; COMMITTEE=SCCNFP; REPORT_DATE=25 May 2004; VALUE_TEXT=50; DOSE=a repeated dose and a sub-chronic toxicity study.; EFFECT=a repeated dose and a sub-chronic toxicity study. Missing values in male control organ and body weights make it difficult to evaluate possible substance-related changes in absolute and relative body weights (repeated dose study). Blue discolouration of the faeces and other body parts was seen in the dose groups 10 and 100 mg/kg bw/day (repeated dose) and in all doses (sub-chronic). No relevant substance-related clinical findings were noted. The NOAEL in the subchronic toxicity study was set at 3 mg/kg bw/day. The NOAEL for maternal toxicity was set at 50 mg/kg bw/day, the NOAEL for teratogenicity was 5 mg/kg bw/day, for embryotoxicity a NOAEL could not be established. Tetrabromophenol Blue is not a skin irritant. Although the neat substance poses a risk of serious damage to the eyes, no effect was noted at the proposed use concentration of 0.2%. Tetrabromophenol Blue is not a sensitiser when used as intended. The percutaneous absorption study is inadequate. Tetrabromophenol has been tested for the induction of gene mutations; CITATION_NUMBERS=[]; DETAILS_JSON={"cas_number":"4430-25-5","citation":"","dose":"a repeated dose and a sub-chronic toxicity study.","duration":"sub-chronic","effect":"a repeated dose and a sub-chronic toxicity study. Missing values in male control organ and body weights make it difficult to evaluate possible substance-related changes in absolute and relative body weights (repeated dose study). Blue discolouration of the faeces and other body parts was seen in the dose groups 10 and 100 mg/kg bw/day (repeated dose) and in all doses (sub-chronic). No relevant substance-related clinical findings were noted. The NOAEL in the subchronic toxicity study was set at 3 mg/kg bw/day. The NOAEL for maternal toxicity was set at 50 mg/kg bw/day, the NOAEL for teratogenicity was 5 mg/kg bw/day, for embryotoxicity a NOAEL could not be established. Tetrabromophenol Blue is not a skin irritant. Although the neat substance poses a risk of serious damage to the eyes, no effect was noted at the proposed use concentration of 0.2%. Tetrabromophenol Blue is not a sensitiser when used as intended. The percutaneous absorption study is inadequate. Tetrabromophenol has been tested for the induction of gene mutations","endpoint":"repeated dose toxicity","ingredient":"s below correspond to the octabromo-derivative only, while the","loael_value":"","noael_unit":"mg/kg bw/day","noael_value":"50","page":16,"route":"","species":"","study_id":"out283_en_noael_008"}
Regulatory source - 10 mg/kg bw/day - - 90-day - SOURCE_SUBDIR=sccs_o_101; REPORT_TITLE=OPINION ON Tetrabromophenol Blue COLIPA n° C183; OPINION_NUMBER=SCCS/1426/11; COMMITTEE=Scientific Committee on Consumer Safety (SCCS); REPORT_DATE=18 September 2012; VALUE_TEXT=10; DOSE=and not considered as toxicologically relevant, but changes in platelet values (males) at 100 mg/kg bw/day and changes in erythrocytes counts observed in males which were statistically significant at 10 and 100 mg/kg bw/day point to a haematotoxic potential of the test substance.; EFFECT=and not considered as toxicologically relevant, but changes in platelet values (males) at 100 mg/kg bw/day and changes in erythrocytes counts observed in males which were statistically significant at 10 and 100 mg/kg bw/day point to a haematotoxic potential of the test substance. Following the dose of 100 mg/kg bw/day changes in urea (males) and cholesterol (females) values were found. Discolouration of the gastro-intestinal tract was observed and related to the staining properties. The study authors established a NOAEL of 10 mg/kg bw/day. Due to the ophthalmological and haematological findings at this dose level, the SCCNFP set the NOAEL to 3 mg/kg bw/day. Ref.: 12 Comment The SCCNFP remarked that according to Ref. 15 (Ref. 5 subm. I), a 2% solution of Tetrabromophenol Blue has not been classified as eye irritating and no corneal opacity was observed at this concentration. However, for the highest dose in this 90-day study 100 mg per kg bw was administered in 5 ml volume per kg, which corresponds to a 2% solution and the observ; CITATION=Ref.: 12 Comment The SCCNFP remarked that according to Ref; CITATION_NUMBERS=[12]; REFERENCE=Ref.: 12 Comment The SCCNFP remarked that according to Ref; DETAILS_JSON={"cas_number":"4430-25-5","citation":"Ref.: 12 Comment The SCCNFP remarked that according to Ref","dose":"and not considered as toxicologically relevant, but changes in platelet values (males) at 100 mg/kg bw/day and changes in erythrocytes counts observed in males which were statistically significant at 10 and 100 mg/kg bw/day point to a haematotoxic potential of the test substance.","duration":"90-day","effect":"and not considered as toxicologically relevant, but changes in platelet values (males) at 100 mg/kg bw/day and changes in erythrocytes counts observed in males which were statistically significant at 10 and 100 mg/kg bw/day point to a haematotoxic potential of the test substance. Following the dose of 100 mg/kg bw/day changes in urea (males) and cholesterol (females) values were found. Discolouration of the gastro-intestinal tract was observed and related to the staining properties. The study authors established a NOAEL of 10 mg/kg bw/day. Due to the ophthalmological and haematological findings at this dose level, the SCCNFP set the NOAEL to 3 mg/kg bw/day. Ref.: 12 Comment The SCCNFP remarked that according to Ref. 15 (Ref. 5 subm. I), a 2% solution of Tetrabromophenol Blue has not been classified as eye irritating and no corneal opacity was observed at this concentration. However, for the highest dose in this 90-day study 100 mg per kg bw was administered in 5 ml volume per kg, which corresponds to a 2% solution and the observ","endpoint":"","ingredient":"Tetrabromophenol Blue","loael_value":"","noael_unit":"mg/kg bw/day","noael_value":"10","page":17,"route":"","species":"","study_id":"sccs_o_101_noael_002"}
Regulatory source - 3 mg/kg bw/day - - 90-day - SOURCE_SUBDIR=sccs_o_101; REPORT_TITLE=OPINION ON Tetrabromophenol Blue COLIPA n° C183; OPINION_NUMBER=SCCS/1426/11; COMMITTEE=Scientific Committee on Consumer Safety (SCCS); REPORT_DATE=18 September 2012; VALUE_TEXT=3; DOSE=erythrocytes counts observed in males which were statistically significant at 10 and 100 mg/kg bw/day point to a haematotoxic potential of the test substance.; EFFECT=erythrocytes counts observed in males which were statistically significant at 10 and 100 mg/kg bw/day point to a haematotoxic potential of the test substance. Following the dose of 100 mg/kg bw/day changes in urea (males) and cholesterol (females) values were found. Discolouration of the gastro-intestinal tract was observed and related to the staining properties. The study authors established a NOAEL of 10 mg/kg bw/day. Due to the ophthalmological and haematological findings at this dose level, the SCCNFP set the NOAEL to 3 mg/kg bw/day. Ref.: 12 Comment The SCCNFP remarked that according to Ref. 15 (Ref. 5 subm. I), a 2% solution of Tetrabromophenol Blue has not been classified as eye irritating and no corneal opacity was observed at this concentration. However, for the highest dose in this 90-day study 100 mg per kg bw was administered in 5 ml volume per kg, which corresponds to a 2% solution and the observed ophthalmological effects were attributed to direct eye contact. Reassessment by the SCCS In 2004, only a draft study; CITATION=Ref.: 12 Comment The SCCNFP remarked that according to Ref; CITATION_NUMBERS=[12]; REFERENCE=Ref.: 12 Comment The SCCNFP remarked that according to Ref; DETAILS_JSON={"cas_number":"4430-25-5","citation":"Ref.: 12 Comment The SCCNFP remarked that according to Ref","dose":"erythrocytes counts observed in males which were statistically significant at 10 and 100 mg/kg bw/day point to a haematotoxic potential of the test substance.","duration":"90-day","effect":"erythrocytes counts observed in males which were statistically significant at 10 and 100 mg/kg bw/day point to a haematotoxic potential of the test substance. Following the dose of 100 mg/kg bw/day changes in urea (males) and cholesterol (females) values were found. Discolouration of the gastro-intestinal tract was observed and related to the staining properties. The study authors established a NOAEL of 10 mg/kg bw/day. Due to the ophthalmological and haematological findings at this dose level, the SCCNFP set the NOAEL to 3 mg/kg bw/day. Ref.: 12 Comment The SCCNFP remarked that according to Ref. 15 (Ref. 5 subm. I), a 2% solution of Tetrabromophenol Blue has not been classified as eye irritating and no corneal opacity was observed at this concentration. However, for the highest dose in this 90-day study 100 mg per kg bw was administered in 5 ml volume per kg, which corresponds to a 2% solution and the observed ophthalmological effects were attributed to direct eye contact. Reassessment by the SCCS In 2004, only a draft study","endpoint":"","ingredient":"Tetrabromophenol Blue","loael_value":"","noael_unit":"mg/kg bw/day","noael_value":"3","page":17,"route":"","species":"","study_id":"sccs_o_101_noael_003"}
Regulatory source - 50 mg/kg bw/day rat - - - SOURCE_SUBDIR=sccs_o_101; REPORT_TITLE=OPINION ON Tetrabromophenol Blue COLIPA n° C183; OPINION_NUMBER=SCCS/1426/11; COMMITTEE=Scientific Committee on Consumer Safety (SCCS); REPORT_DATE=18 September 2012; VALUE_TEXT=50; DOSE=half of the 50 mg/kg dose.; EFFECT=half of the 50 mg/kg dose. At the low dose 5 mg/kg bw/day a generalised reduction in ossification was seen. Incidental cases of malformations were seen in all dose groups including controls (e.g. polydactyly, exencephaly, spina bifida, abnormal shape of limb bones) but the effects were not dose-related. In the high dose group 18 of 166 analysed foetuses showed changes of the major arteries which should be attributed to treatment. Even in the medium dose one foetus with persistent truncus arteriosus was found. The NOAEL of maternal toxicity was 50 mg/kg bw/day, the NOAEL of teratogenicity was 5 mg/kg bw/day. For embryotoxicity, a NOAEL cannot be established. Ref.: 17 New study, submission 2005 Guideline: OECD no. 414 (2001) Species/strain: Rat, strain Wistar rats HanBrl: WIST, outbred (SPF) Group size: 22 mated females per dose group Test item: Tetrabromophenol Blue Batch: TBFB3/02/30 Purity: 98.8 area % (at 615 nm, HPLC) Dose levels: 0, 3, 30 and 300 mg/kg bw/day Vehicle: 5% w/w polyglycol 600, 4% w/w Plantaren 2000 UP (50% a; CITATION=Ref.: 17 New study, submission 2005 Guideline: OECD no; CITATION_NUMBERS=[17,2005]; REFERENCE=Ref.: 17 New study, submission 2005 Guideline: OECD no; DETAILS_JSON={"cas_number":"4430-25-5","citation":"Ref.: 17 New study, submission 2005 Guideline: OECD no","dose":"half of the 50 mg/kg dose.","duration":"","effect":"half of the 50 mg/kg dose. At the low dose 5 mg/kg bw/day a generalised reduction in ossification was seen. Incidental cases of malformations were seen in all dose groups including controls (e.g. polydactyly, exencephaly, spina bifida, abnormal shape of limb bones) but the effects were not dose-related. In the high dose group 18 of 166 analysed foetuses showed changes of the major arteries which should be attributed to treatment. Even in the medium dose one foetus with persistent truncus arteriosus was found. The NOAEL of maternal toxicity was 50 mg/kg bw/day, the NOAEL of teratogenicity was 5 mg/kg bw/day. For embryotoxicity, a NOAEL cannot be established. Ref.: 17 New study, submission 2005 Guideline: OECD no. 414 (2001) Species/strain: Rat, strain Wistar rats HanBrl: WIST, outbred (SPF) Group size: 22 mated females per dose group Test item: Tetrabromophenol Blue Batch: TBFB3/02/30 Purity: 98.8 area % (at 615 nm, HPLC) Dose levels: 0, 3, 30 and 300 mg/kg bw/day Vehicle: 5% w/w polyglycol 600, 4% w/w Plantaren 2000 UP (50% a","endpoint":"","ingredient":"Tetrabromophenol Blue","loael_value":"","noael_unit":"mg/kg bw/day","noael_value":"50","page":21,"route":"","species":"rat","study_id":"sccs_o_101_noael_004"}
Regulatory source - 50 mg/kg bw/day rat - - - SOURCE_SUBDIR=sccs_o_101; REPORT_TITLE=OPINION ON Tetrabromophenol Blue COLIPA n° C183; OPINION_NUMBER=SCCS/1426/11; COMMITTEE=Scientific Committee on Consumer Safety (SCCS); REPORT_DATE=18 September 2012; VALUE_TEXT=50; DOSE=Incidental cases of malformations were seen in all dose groups including controls (e.g. polydactyly, exencephaly, spina bifida, abnormal shape of limb bones) but the effects were not dose-related.; EFFECT=w/day a generalised reduction in ossification was seen. Incidental cases of malformations were seen in all dose groups including controls (e.g. polydactyly, exencephaly, spina bifida, abnormal shape of limb bones) but the effects were not dose-related. In the high dose group 18 of 166 analysed foetuses showed changes of the major arteries which should be attributed to treatment. Even in the medium dose one foetus with persistent truncus arteriosus was found. The NOAEL of maternal toxicity was 50 mg/kg bw/day, the NOAEL of teratogenicity was 5 mg/kg bw/day. For embryotoxicity, a NOAEL cannot be established. Ref.: 17 New study, submission 2005 Guideline: OECD no. 414 (2001) Species/strain: Rat, strain Wistar rats HanBrl: WIST, outbred (SPF) Group size: 22 mated females per dose group Test item: Tetrabromophenol Blue Batch: TBFB3/02/30 Purity: 98.8 area % (at 615 nm, HPLC) Dose levels: 0, 3, 30 and 300 mg/kg bw/day Vehicle: 5% w/w polyglycol 600, 4% w/w Plantaren 2000 UP (50% aqueous; CITATION=Ref.: 17 New study, submission 2005 Guideline: OECD no; CITATION_NUMBERS=[17,2005]; REFERENCE=Ref.: 17 New study, submission 2005 Guideline: OECD no; DETAILS_JSON={"cas_number":"4430-25-5","citation":"Ref.: 17 New study, submission 2005 Guideline: OECD no","dose":"Incidental cases of malformations were seen in all dose groups including controls (e.g. polydactyly, exencephaly, spina bifida, abnormal shape of limb bones) but the effects were not dose-related.","duration":"","effect":"w/day a generalised reduction in ossification was seen. Incidental cases of malformations were seen in all dose groups including controls (e.g. polydactyly, exencephaly, spina bifida, abnormal shape of limb bones) but the effects were not dose-related. In the high dose group 18 of 166 analysed foetuses showed changes of the major arteries which should be attributed to treatment. Even in the medium dose one foetus with persistent truncus arteriosus was found. The NOAEL of maternal toxicity was 50 mg/kg bw/day, the NOAEL of teratogenicity was 5 mg/kg bw/day. For embryotoxicity, a NOAEL cannot be established. Ref.: 17 New study, submission 2005 Guideline: OECD no. 414 (2001) Species/strain: Rat, strain Wistar rats HanBrl: WIST, outbred (SPF) Group size: 22 mated females per dose group Test item: Tetrabromophenol Blue Batch: TBFB3/02/30 Purity: 98.8 area % (at 615 nm, HPLC) Dose levels: 0, 3, 30 and 300 mg/kg bw/day Vehicle: 5% w/w polyglycol 600, 4% w/w Plantaren 2000 UP (50% aqueous","endpoint":"","ingredient":"Tetrabromophenol Blue","loael_value":"","noael_unit":"mg/kg bw/day","noael_value":"50","page":21,"route":"","species":"rat","study_id":"sccs_o_101_noael_005"}
Regulatory source - 5 mg/kg bw/day rat - - - SOURCE_SUBDIR=sccs_o_101; REPORT_TITLE=OPINION ON Tetrabromophenol Blue COLIPA n° C183; OPINION_NUMBER=SCCS/1426/11; COMMITTEE=Scientific Committee on Consumer Safety (SCCS); REPORT_DATE=18 September 2012; VALUE_TEXT=5; DOSE=cases of malformations were seen in all dose groups including controls (e.g. polydactyly, exencephaly, spina bifida, abnormal shape of limb bones) but the effects were not dose-related.; EFFECT=cases of malformations were seen in all dose groups including controls (e.g. polydactyly, exencephaly, spina bifida, abnormal shape of limb bones) but the effects were not dose-related. In the high dose group 18 of 166 analysed foetuses showed changes of the major arteries which should be attributed to treatment. Even in the medium dose one foetus with persistent truncus arteriosus was found. The NOAEL of maternal toxicity was 50 mg/kg bw/day, the NOAEL of teratogenicity was 5 mg/kg bw/day. For embryotoxicity, a NOAEL cannot be established. Ref.: 17 New study, submission 2005 Guideline: OECD no. 414 (2001) Species/strain: Rat, strain Wistar rats HanBrl: WIST, outbred (SPF) Group size: 22 mated females per dose group Test item: Tetrabromophenol Blue Batch: TBFB3/02/30 Purity: 98.8 area % (at 615 nm, HPLC) Dose levels: 0, 3, 30 and 300 mg/kg bw/day Vehicle: 5% w/w polyglycol 600, 4% w/w Plantaren 2000 UP (50% aqueous; CITATION=Ref.: 17 New study, submission 2005 Guideline: OECD no; CITATION_NUMBERS=[17,2005]; REFERENCE=Ref.: 17 New study, submission 2005 Guideline: OECD no; DETAILS_JSON={"cas_number":"4430-25-5","citation":"Ref.: 17 New study, submission 2005 Guideline: OECD no","dose":"cases of malformations were seen in all dose groups including controls (e.g. polydactyly, exencephaly, spina bifida, abnormal shape of limb bones) but the effects were not dose-related.","duration":"","effect":"cases of malformations were seen in all dose groups including controls (e.g. polydactyly, exencephaly, spina bifida, abnormal shape of limb bones) but the effects were not dose-related. In the high dose group 18 of 166 analysed foetuses showed changes of the major arteries which should be attributed to treatment. Even in the medium dose one foetus with persistent truncus arteriosus was found. The NOAEL of maternal toxicity was 50 mg/kg bw/day, the NOAEL of teratogenicity was 5 mg/kg bw/day. For embryotoxicity, a NOAEL cannot be established. Ref.: 17 New study, submission 2005 Guideline: OECD no. 414 (2001) Species/strain: Rat, strain Wistar rats HanBrl: WIST, outbred (SPF) Group size: 22 mated females per dose group Test item: Tetrabromophenol Blue Batch: TBFB3/02/30 Purity: 98.8 area % (at 615 nm, HPLC) Dose levels: 0, 3, 30 and 300 mg/kg bw/day Vehicle: 5% w/w polyglycol 600, 4% w/w Plantaren 2000 UP (50% aqueous","endpoint":"","ingredient":"Tetrabromophenol Blue","loael_value":"","noael_unit":"mg/kg bw/day","noael_value":"5","page":21,"route":"","species":"rat","study_id":"sccs_o_101_noael_006"}
Regulatory source - 30 mg/kg bw/ day rat - - - SOURCE_SUBDIR=sccs_o_101; REPORT_TITLE=OPINION ON Tetrabromophenol Blue COLIPA n° C183; OPINION_NUMBER=SCCS/1426/11; COMMITTEE=Scientific Committee on Consumer Safety (SCCS); REPORT_DATE=18 September 2012; VALUE_TEXT=30; DOSE=d incidences of left-sided umbilical arteries and cranially elongated thymuses at the high dose and anophthalmia in the mid dose group.; EFFECT=d incidences of left-sided umbilical arteries and cranially elongated thymuses at the high dose and anophthalmia in the mid dose group. There was an increased incidence of fused zygomatic arches at the high dose (21 in 12 litters) when compared with the control group (12 in 9 litters). A statistically significant increase in supernumerary rudimentary ribs was observed in the mid and high doses. No changes were noted in the foetuses of the low dose group (3 mg/kg bw). Conclusion Based on these results the maternal NOAEL was considered to be 30 mg/kg bw/ day. A NOAEL for embryo-foetal effects was derived at 3 mg/kg bw/day. Ref: 18 3.3.9. Toxicokinetics Guideline: OECD 417 (1984) and OECD 427 (2004) Species/strain: Rat, Wistar CRL: WI BR (outbreed) (SPF) Group size: Females, mass balance groups (groups 1,2,3,4) 4 per dose; toxicokinetics groups (groups 5, 6, 7, 8) 6 per dose Test substances: Tetrabromophenol Blue-(Phenol-UL-14C) Batch: 064K9418 non-labelled Tetrabromophenol Blue Batch: TBFB3/02/30 Purity: Radiochemical purity: 88; CITATION=Ref: 18 3; CITATION_NUMBERS=[18,3]; REFERENCE=Ref: 18 3; DETAILS_JSON={"cas_number":"4430-25-5","citation":"Ref: 18 3","dose":"d incidences of left-sided umbilical arteries and cranially elongated thymuses at the high dose and anophthalmia in the mid dose group.","duration":"","effect":"d incidences of left-sided umbilical arteries and cranially elongated thymuses at the high dose and anophthalmia in the mid dose group. There was an increased incidence of fused zygomatic arches at the high dose (21 in 12 litters) when compared with the control group (12 in 9 litters). A statistically significant increase in supernumerary rudimentary ribs was observed in the mid and high doses. No changes were noted in the foetuses of the low dose group (3 mg/kg bw). Conclusion Based on these results the maternal NOAEL was considered to be 30 mg/kg bw/ day. A NOAEL for embryo-foetal effects was derived at 3 mg/kg bw/day. Ref: 18 3.3.9. Toxicokinetics Guideline: OECD 417 (1984) and OECD 427 (2004) Species/strain: Rat, Wistar CRL: WI BR (outbreed) (SPF) Group size: Females, mass balance groups (groups 1,2,3,4) 4 per dose; toxicokinetics groups (groups 5, 6, 7, 8) 6 per dose Test substances: Tetrabromophenol Blue-(Phenol-UL-14C) Batch: 064K9418 non-labelled Tetrabromophenol Blue Batch: TBFB3/02/30 Purity: Radiochemical purity: 88","endpoint":"","ingredient":"Tetrabromophenol Blue","loael_value":"","noael_unit":"mg/kg bw/ day","noael_value":"30","page":23,"route":"","species":"rat","study_id":"sccs_o_101_noael_007"}
Regulatory source - 30 mg/kg bw/ day rat - - - SOURCE_SUBDIR=sccs_o_101; REPORT_TITLE=OPINION ON Tetrabromophenol Blue COLIPA n° C183; OPINION_NUMBER=SCCS/1426/11; COMMITTEE=Scientific Committee on Consumer Safety (SCCS); REPORT_DATE=18 September 2012; VALUE_TEXT=30; DOSE=nd cranially elongated thymuses at the high dose and anophthalmia in the mid dose group.; EFFECT=nd cranially elongated thymuses at the high dose and anophthalmia in the mid dose group. There was an increased incidence of fused zygomatic arches at the high dose (21 in 12 litters) when compared with the control group (12 in 9 litters). A statistically significant increase in supernumerary rudimentary ribs was observed in the mid and high doses. No changes were noted in the foetuses of the low dose group (3 mg/kg bw). Conclusion Based on these results the maternal NOAEL was considered to be 30 mg/kg bw/ day. A NOAEL for embryo-foetal effects was derived at 3 mg/kg bw/day. Ref: 18 3.3.9. Toxicokinetics Guideline: OECD 417 (1984) and OECD 427 (2004) Species/strain: Rat, Wistar CRL: WI BR (outbreed) (SPF) Group size: Females, mass balance groups (groups 1,2,3,4) 4 per dose; toxicokinetics groups (groups 5, 6, 7, 8) 6 per dose Test substances: Tetrabromophenol Blue-(Phenol-UL-14C) Batch: 064K9418 non-labelled Tetrabromophenol Blue Batch: TBFB3/02/30 Purity: Radiochemical purity: 88.8% by HPLC, specific activity 48.8 mCi/mmol No; CITATION=Ref: 18 3; CITATION_NUMBERS=[18,3]; REFERENCE=Ref: 18 3; DETAILS_JSON={"cas_number":"4430-25-5","citation":"Ref: 18 3","dose":"nd cranially elongated thymuses at the high dose and anophthalmia in the mid dose group.","duration":"","effect":"nd cranially elongated thymuses at the high dose and anophthalmia in the mid dose group. There was an increased incidence of fused zygomatic arches at the high dose (21 in 12 litters) when compared with the control group (12 in 9 litters). A statistically significant increase in supernumerary rudimentary ribs was observed in the mid and high doses. No changes were noted in the foetuses of the low dose group (3 mg/kg bw). Conclusion Based on these results the maternal NOAEL was considered to be 30 mg/kg bw/ day. A NOAEL for embryo-foetal effects was derived at 3 mg/kg bw/day. Ref: 18 3.3.9. Toxicokinetics Guideline: OECD 417 (1984) and OECD 427 (2004) Species/strain: Rat, Wistar CRL: WI BR (outbreed) (SPF) Group size: Females, mass balance groups (groups 1,2,3,4) 4 per dose; toxicokinetics groups (groups 5, 6, 7, 8) 6 per dose Test substances: Tetrabromophenol Blue-(Phenol-UL-14C) Batch: 064K9418 non-labelled Tetrabromophenol Blue Batch: TBFB3/02/30 Purity: Radiochemical purity: 88.8% by HPLC, specific activity 48.8 mCi/mmol No","endpoint":"","ingredient":"Tetrabromophenol Blue","loael_value":"","noael_unit":"mg/kg bw/ day","noael_value":"30","page":23,"route":"","species":"rat","study_id":"sccs_o_101_noael_008"}
Regulatory source - 100 mg/kg bw/day - - 90-day - SOURCE_SUBDIR=sccs_o_232; REPORT_TITLE=Final Opinion Version S Scientific Committee on Consumer Safety SCCS OPINION ON Tetrabromophenol Blue, 4,4’-(4,5,6,7-tetrabromo-1,1- dioxido-3H-2,1-benzoxathiol-3-yliden)bis-2,6-; OPINION_NUMBER=SCCS/1610/19; COMMITTEE=Scientific Committee on Consumer Safety (SCCS); REPORT_DATE=final version of 13 December 2019; VALUE_TEXT=100; DOSE=rocytes counts observed in males which were statistically significant at 10 and 100 mg/kg bw/day point to a haematotoxic potential of the test substance.; EFFECT=rocytes counts observed in males which were statistically significant at 10 and 100 mg/kg bw/day point to a haematotoxic potential of the test substance. Following the dose of 100 mg/kg bw/day changes in urea (males) and cholesterol (females) values were found. Discolouration of the gastro-intestinal tract was observed, related to the staining properties. No treatment-related changes were observed in organ weights or in the histopathological examination of organs and tissues. The study report authors established a NOAEL of 100 mg/kg bw/day. Due to the ophthalmological and haematological findings at this dose level, the SCCNFP set the NOAEL to 3 mg/kg bw/day. Ref.: 1 (Submission I) Ref.: 1 (Submission II) SCCS comment The SCCNFP remarked that according to Ref. 15 (Ref. 5 subm. I), a 2% solution of Tetrabromophenol Blue has not been classified as eye irritating and no corneal opacity was observed at this concentration. However, for the highest dose in this 90-day study, 100 mg per kg bw was administered in 5 ml volume per kg, whi; CITATION=Ref.: 1 (Submission I) Ref; CITATION_NUMBERS=[1]; REFERENCE=Ref.: 1 (Submission I) Ref; DETAILS_JSON={"cas_number":"4430-25-5","citation":"Ref.: 1 (Submission I) Ref","dose":"rocytes counts observed in males which were statistically significant at 10 and 100 mg/kg bw/day point to a haematotoxic potential of the test substance.","duration":"90-day","effect":"rocytes counts observed in males which were statistically significant at 10 and 100 mg/kg bw/day point to a haematotoxic potential of the test substance. Following the dose of 100 mg/kg bw/day changes in urea (males) and cholesterol (females) values were found. Discolouration of the gastro-intestinal tract was observed, related to the staining properties. No treatment-related changes were observed in organ weights or in the histopathological examination of organs and tissues. The study report authors established a NOAEL of 100 mg/kg bw/day. Due to the ophthalmological and haematological findings at this dose level, the SCCNFP set the NOAEL to 3 mg/kg bw/day. Ref.: 1 (Submission I) Ref.: 1 (Submission II) SCCS comment The SCCNFP remarked that according to Ref. 15 (Ref. 5 subm. I), a 2% solution of Tetrabromophenol Blue has not been classified as eye irritating and no corneal opacity was observed at this concentration. However, for the highest dose in this 90-day study, 100 mg per kg bw was administered in 5 ml volume per kg, whi","endpoint":"","ingredient":"Tetrabromophenol Blue","loael_value":"","noael_unit":"mg/kg bw/day","noael_value":"100","page":31,"route":"","species":"","study_id":"sccs_o_232_noael_002"}
Regulatory source - 3 mg/kg bw/day - - 90-day - SOURCE_SUBDIR=sccs_o_232; REPORT_TITLE=Final Opinion Version S Scientific Committee on Consumer Safety SCCS OPINION ON Tetrabromophenol Blue, 4,4’-(4,5,6,7-tetrabromo-1,1- dioxido-3H-2,1-benzoxathiol-3-yliden)bis-2,6-; OPINION_NUMBER=SCCS/1610/19; COMMITTEE=Scientific Committee on Consumer Safety (SCCS); REPORT_DATE=final version of 13 December 2019; VALUE_TEXT=3; DOSE=Following the dose of 100 mg/kg bw/day changes in urea (males) and cholesterol (females) values were found.; EFFECT=otential of the test substance. Following the dose of 100 mg/kg bw/day changes in urea (males) and cholesterol (females) values were found. Discolouration of the gastro-intestinal tract was observed, related to the staining properties. No treatment-related changes were observed in organ weights or in the histopathological examination of organs and tissues. The study report authors established a NOAEL of 100 mg/kg bw/day. Due to the ophthalmological and haematological findings at this dose level, the SCCNFP set the NOAEL to 3 mg/kg bw/day. Ref.: 1 (Submission I) Ref.: 1 (Submission II) SCCS comment The SCCNFP remarked that according to Ref. 15 (Ref. 5 subm. I), a 2% solution of Tetrabromophenol Blue has not been classified as eye irritating and no corneal opacity was observed at this concentration. However, for the highest dose in this 90-day study, 100 mg per kg bw was administered in 5 ml volume per kg, which corresponds to a 2% solution and the observed ophthalmological effects were attributed to direct eye contact. Reassess; CITATION=Ref.: 1 (Submission I) Ref; CITATION_NUMBERS=[1]; REFERENCE=Ref.: 1 (Submission I) Ref; DETAILS_JSON={"cas_number":"4430-25-5","citation":"Ref.: 1 (Submission I) Ref","dose":"Following the dose of 100 mg/kg bw/day changes in urea (males) and cholesterol (females) values were found.","duration":"90-day","effect":"otential of the test substance. Following the dose of 100 mg/kg bw/day changes in urea (males) and cholesterol (females) values were found. Discolouration of the gastro-intestinal tract was observed, related to the staining properties. No treatment-related changes were observed in organ weights or in the histopathological examination of organs and tissues. The study report authors established a NOAEL of 100 mg/kg bw/day. Due to the ophthalmological and haematological findings at this dose level, the SCCNFP set the NOAEL to 3 mg/kg bw/day. Ref.: 1 (Submission I) Ref.: 1 (Submission II) SCCS comment The SCCNFP remarked that according to Ref. 15 (Ref. 5 subm. I), a 2% solution of Tetrabromophenol Blue has not been classified as eye irritating and no corneal opacity was observed at this concentration. However, for the highest dose in this 90-day study, 100 mg per kg bw was administered in 5 ml volume per kg, which corresponds to a 2% solution and the observed ophthalmological effects were attributed to direct eye contact. Reassess","endpoint":"","ingredient":"Tetrabromophenol Blue","loael_value":"","noael_unit":"mg/kg bw/day","noael_value":"3","page":31,"route":"","species":"","study_id":"sccs_o_232_noael_003"}
Regulatory source - 50 mg/kg bw/day - - - - SOURCE_SUBDIR=sccs_o_232; REPORT_TITLE=Final Opinion Version S Scientific Committee on Consumer Safety SCCS OPINION ON Tetrabromophenol Blue, 4,4’-(4,5,6,7-tetrabromo-1,1- dioxido-3H-2,1-benzoxathiol-3-yliden)bis-2,6-; OPINION_NUMBER=SCCS/1610/19; COMMITTEE=Scientific Committee on Consumer Safety (SCCS); REPORT_DATE=final version of 13 December 2019; VALUE_TEXT=50; DOSE=At the low dose of 5 mg/kg bw/day, a generalised reduction in ossification was seen.; EFFECT=g dose. At the low dose of 5 mg/kg bw/day, a generalised reduction in ossification was seen. Incidental cases of malformations were seen in all dose groups including controls (e.g. polydactyly, exencephaly, spina bifida, abnormal shape of limb bones) but the effects were not dose-related. In the high- dose group, 18 of 166 analysed foetuses showed changes of the major arteries, which should be attributed to treatment. Even in the medium dose, one foetus with persistent truncus arteriosus was found. Conclusion The NOAEL of maternal toxicity was 50 mg/kg bw/day, the NOAEL of teratogenicity was 5 mg/kg bw/day. For embryotoxicity, a NOAEL cannot be established. Ref.: 6 (submission I) Ref.: 6 (Submission II); CITATION=Ref.: 6 (submission I) Ref; CITATION_NUMBERS=[6]; REFERENCE=Ref.: 6 (submission I) Ref; DETAILS_JSON={"cas_number":"4430-25-5","citation":"Ref.: 6 (submission I) Ref","dose":"At the low dose of 5 mg/kg bw/day, a generalised reduction in ossification was seen.","duration":"","effect":"g dose. At the low dose of 5 mg/kg bw/day, a generalised reduction in ossification was seen. Incidental cases of malformations were seen in all dose groups including controls (e.g. polydactyly, exencephaly, spina bifida, abnormal shape of limb bones) but the effects were not dose-related. In the high- dose group, 18 of 166 analysed foetuses showed changes of the major arteries, which should be attributed to treatment. Even in the medium dose, one foetus with persistent truncus arteriosus was found. Conclusion The NOAEL of maternal toxicity was 50 mg/kg bw/day, the NOAEL of teratogenicity was 5 mg/kg bw/day. For embryotoxicity, a NOAEL cannot be established. Ref.: 6 (submission I) Ref.: 6 (Submission II)","endpoint":"","ingredient":"Tetrabromophenol Blue","loael_value":"","noael_unit":"mg/kg bw/day","noael_value":"50","page":40,"route":"","species":"","study_id":"sccs_o_232_noael_009"}
Regulatory source - 50 mg/kg bw/day - - - - SOURCE_SUBDIR=sccs_o_232; REPORT_TITLE=Final Opinion Version S Scientific Committee on Consumer Safety SCCS OPINION ON Tetrabromophenol Blue, 4,4’-(4,5,6,7-tetrabromo-1,1- dioxido-3H-2,1-benzoxathiol-3-yliden)bis-2,6-; OPINION_NUMBER=SCCS/1610/19; COMMITTEE=Scientific Committee on Consumer Safety (SCCS); REPORT_DATE=final version of 13 December 2019; VALUE_TEXT=50; DOSE=Incidental cases of malformations were seen in all dose groups including controls (e.g. polydactyly, exencephaly, spina bifida, abnormal shape of limb bones) but the effects were not dose-related.; EFFECT=ised reduction in ossification was seen. Incidental cases of malformations were seen in all dose groups including controls (e.g. polydactyly, exencephaly, spina bifida, abnormal shape of limb bones) but the effects were not dose-related. In the high- dose group, 18 of 166 analysed foetuses showed changes of the major arteries, which should be attributed to treatment. Even in the medium dose, one foetus with persistent truncus arteriosus was found. Conclusion The NOAEL of maternal toxicity was 50 mg/kg bw/day, the NOAEL of teratogenicity was 5 mg/kg bw/day. For embryotoxicity, a NOAEL cannot be established. Ref.: 6 (submission I) Ref.: 6 (Submission II); CITATION=Ref.: 6 (submission I) Ref; CITATION_NUMBERS=[6]; REFERENCE=Ref.: 6 (submission I) Ref; DETAILS_JSON={"cas_number":"4430-25-5","citation":"Ref.: 6 (submission I) Ref","dose":"Incidental cases of malformations were seen in all dose groups including controls (e.g. polydactyly, exencephaly, spina bifida, abnormal shape of limb bones) but the effects were not dose-related.","duration":"","effect":"ised reduction in ossification was seen. Incidental cases of malformations were seen in all dose groups including controls (e.g. polydactyly, exencephaly, spina bifida, abnormal shape of limb bones) but the effects were not dose-related. In the high- dose group, 18 of 166 analysed foetuses showed changes of the major arteries, which should be attributed to treatment. Even in the medium dose, one foetus with persistent truncus arteriosus was found. Conclusion The NOAEL of maternal toxicity was 50 mg/kg bw/day, the NOAEL of teratogenicity was 5 mg/kg bw/day. For embryotoxicity, a NOAEL cannot be established. Ref.: 6 (submission I) Ref.: 6 (Submission II)","endpoint":"","ingredient":"Tetrabromophenol Blue","loael_value":"","noael_unit":"mg/kg bw/day","noael_value":"50","page":40,"route":"","species":"","study_id":"sccs_o_232_noael_010"}
Regulatory source - 5 mg/kg bw/day - - - - SOURCE_SUBDIR=sccs_o_232; REPORT_TITLE=Final Opinion Version S Scientific Committee on Consumer Safety SCCS OPINION ON Tetrabromophenol Blue, 4,4’-(4,5,6,7-tetrabromo-1,1- dioxido-3H-2,1-benzoxathiol-3-yliden)bis-2,6-; OPINION_NUMBER=SCCS/1610/19; COMMITTEE=Scientific Committee on Consumer Safety (SCCS); REPORT_DATE=final version of 13 December 2019; VALUE_TEXT=5; DOSE=rmations were seen in all dose groups including controls (e.g. polydactyly, exencephaly, spina bifida, abnormal shape of limb bones) but the effects were not dose-related.; EFFECT=rmations were seen in all dose groups including controls (e.g. polydactyly, exencephaly, spina bifida, abnormal shape of limb bones) but the effects were not dose-related. In the high- dose group, 18 of 166 analysed foetuses showed changes of the major arteries, which should be attributed to treatment. Even in the medium dose, one foetus with persistent truncus arteriosus was found. Conclusion The NOAEL of maternal toxicity was 50 mg/kg bw/day, the NOAEL of teratogenicity was 5 mg/kg bw/day. For embryotoxicity, a NOAEL cannot be established. Ref.: 6 (submission I) Ref.: 6 (Submission II); CITATION=Ref.: 6 (submission I) Ref; CITATION_NUMBERS=[6]; REFERENCE=Ref.: 6 (submission I) Ref; DETAILS_JSON={"cas_number":"4430-25-5","citation":"Ref.: 6 (submission I) Ref","dose":"rmations were seen in all dose groups including controls (e.g. polydactyly, exencephaly, spina bifida, abnormal shape of limb bones) but the effects were not dose-related.","duration":"","effect":"rmations were seen in all dose groups including controls (e.g. polydactyly, exencephaly, spina bifida, abnormal shape of limb bones) but the effects were not dose-related. In the high- dose group, 18 of 166 analysed foetuses showed changes of the major arteries, which should be attributed to treatment. Even in the medium dose, one foetus with persistent truncus arteriosus was found. Conclusion The NOAEL of maternal toxicity was 50 mg/kg bw/day, the NOAEL of teratogenicity was 5 mg/kg bw/day. For embryotoxicity, a NOAEL cannot be established. Ref.: 6 (submission I) Ref.: 6 (Submission II)","endpoint":"","ingredient":"Tetrabromophenol Blue","loael_value":"","noael_unit":"mg/kg bw/day","noael_value":"5","page":40,"route":"","species":"","study_id":"sccs_o_232_noael_011"}
Regulatory source - 30 mg/kg bw/ day rat - - - SOURCE_SUBDIR=sccs_o_232; REPORT_TITLE=Final Opinion Version S Scientific Committee on Consumer Safety SCCS OPINION ON Tetrabromophenol Blue, 4,4’-(4,5,6,7-tetrabromo-1,1- dioxido-3H-2,1-benzoxathiol-3-yliden)bis-2,6-; OPINION_NUMBER=SCCS/1610/19; COMMITTEE=Scientific Committee on Consumer Safety (SCCS); REPORT_DATE=final version of 13 December 2019; VALUE_TEXT=30; DOSE=incidences of left-sided umbilical arteries and cranially elongated thymuses at the high dose and anophthalmia in the mid-dose group.; EFFECT=incidences of left-sided umbilical arteries and cranially elongated thymuses at the high dose and anophthalmia in the mid-dose group. There was an increased incidence of fused zygomatic arches at the high dose (21 in 12 litters) when compared with the control group (12 in 9 litters). A statistically significant increase in supernumerary rudimentary ribs was observed in the mid and high doses. No changes were noted in the foetuses of the low dose group (3 mg/kg bw). Conclusion Based on these results, the maternal NOAEL was considered to be 30 mg/kg bw/ day. A NOAEL for embryo-foetal effects was derived at 3 mg/kg bw/day. Ref: 7 (Submission II) 3.3.9. Toxicokinetics 3.3.9.1. Toxicokinetics in laboratory animals Taken from Submission II Guideline: OECD 417 (1984) and OECD 427 (2004) Species/strain: Rat, Wistar CRL: WI BR (outbreed) (SPF) Group size: Females, mass balance groups (groups 1,2,3,4) 4 per dose; toxicokinetics groups (groups 5, 6, 7, 8) 6 per dose Test substances: Tetrabromophenol Blue-(Phenol-UL-14C) Batch: 064K941; CITATION=Ref: 7 (Submission II) 3; CITATION_NUMBERS=[7,3]; REFERENCE=Ref: 7 (Submission II) 3; DETAILS_JSON={"cas_number":"4430-25-5","citation":"Ref: 7 (Submission II) 3","dose":"incidences of left-sided umbilical arteries and cranially elongated thymuses at the high dose and anophthalmia in the mid-dose group.","duration":"","effect":"incidences of left-sided umbilical arteries and cranially elongated thymuses at the high dose and anophthalmia in the mid-dose group. There was an increased incidence of fused zygomatic arches at the high dose (21 in 12 litters) when compared with the control group (12 in 9 litters). A statistically significant increase in supernumerary rudimentary ribs was observed in the mid and high doses. No changes were noted in the foetuses of the low dose group (3 mg/kg bw). Conclusion Based on these results, the maternal NOAEL was considered to be 30 mg/kg bw/ day. A NOAEL for embryo-foetal effects was derived at 3 mg/kg bw/day. Ref: 7 (Submission II) 3.3.9. Toxicokinetics 3.3.9.1. Toxicokinetics in laboratory animals Taken from Submission II Guideline: OECD 417 (1984) and OECD 427 (2004) Species/strain: Rat, Wistar CRL: WI BR (outbreed) (SPF) Group size: Females, mass balance groups (groups 1,2,3,4) 4 per dose; toxicokinetics groups (groups 5, 6, 7, 8) 6 per dose Test substances: Tetrabromophenol Blue-(Phenol-UL-14C) Batch: 064K941","endpoint":"","ingredient":"Tetrabromophenol Blue","loael_value":"","noael_unit":"mg/kg bw/ day","noael_value":"30","page":42,"route":"","species":"rat","study_id":"sccs_o_232_noael_012"}
Regulatory source - 30 mg/kg bw/ day rat - - - SOURCE_SUBDIR=sccs_o_232; REPORT_TITLE=Final Opinion Version S Scientific Committee on Consumer Safety SCCS OPINION ON Tetrabromophenol Blue, 4,4’-(4,5,6,7-tetrabromo-1,1- dioxido-3H-2,1-benzoxathiol-3-yliden)bis-2,6-; OPINION_NUMBER=SCCS/1610/19; COMMITTEE=Scientific Committee on Consumer Safety (SCCS); REPORT_DATE=final version of 13 December 2019; VALUE_TEXT=30; DOSE=d cranially elongated thymuses at the high dose and anophthalmia in the mid-dose group.; EFFECT=d cranially elongated thymuses at the high dose and anophthalmia in the mid-dose group. There was an increased incidence of fused zygomatic arches at the high dose (21 in 12 litters) when compared with the control group (12 in 9 litters). A statistically significant increase in supernumerary rudimentary ribs was observed in the mid and high doses. No changes were noted in the foetuses of the low dose group (3 mg/kg bw). Conclusion Based on these results, the maternal NOAEL was considered to be 30 mg/kg bw/ day. A NOAEL for embryo-foetal effects was derived at 3 mg/kg bw/day. Ref: 7 (Submission II) 3.3.9. Toxicokinetics 3.3.9.1. Toxicokinetics in laboratory animals Taken from Submission II Guideline: OECD 417 (1984) and OECD 427 (2004) Species/strain: Rat, Wistar CRL: WI BR (outbreed) (SPF) Group size: Females, mass balance groups (groups 1,2,3,4) 4 per dose; toxicokinetics groups (groups 5, 6, 7, 8) 6 per dose Test substances: Tetrabromophenol Blue-(Phenol-UL-14C) Batch: 064K9418 non-labelled Tetrabromophenol Blue Batch: TBF; CITATION=Ref: 7 (Submission II) 3; CITATION_NUMBERS=[7,3]; REFERENCE=Ref: 7 (Submission II) 3; DETAILS_JSON={"cas_number":"4430-25-5","citation":"Ref: 7 (Submission II) 3","dose":"d cranially elongated thymuses at the high dose and anophthalmia in the mid-dose group.","duration":"","effect":"d cranially elongated thymuses at the high dose and anophthalmia in the mid-dose group. There was an increased incidence of fused zygomatic arches at the high dose (21 in 12 litters) when compared with the control group (12 in 9 litters). A statistically significant increase in supernumerary rudimentary ribs was observed in the mid and high doses. No changes were noted in the foetuses of the low dose group (3 mg/kg bw). Conclusion Based on these results, the maternal NOAEL was considered to be 30 mg/kg bw/ day. A NOAEL for embryo-foetal effects was derived at 3 mg/kg bw/day. Ref: 7 (Submission II) 3.3.9. Toxicokinetics 3.3.9.1. Toxicokinetics in laboratory animals Taken from Submission II Guideline: OECD 417 (1984) and OECD 427 (2004) Species/strain: Rat, Wistar CRL: WI BR (outbreed) (SPF) Group size: Females, mass balance groups (groups 1,2,3,4) 4 per dose; toxicokinetics groups (groups 5, 6, 7, 8) 6 per dose Test substances: Tetrabromophenol Blue-(Phenol-UL-14C) Batch: 064K9418 non-labelled Tetrabromophenol Blue Batch: TBF","endpoint":"","ingredient":"Tetrabromophenol Blue","loael_value":"","noael_unit":"mg/kg bw/ day","noael_value":"30","page":42,"route":"","species":"rat","study_id":"sccs_o_232_noael_013"}
Regulatory source - 3 mg/kg bw/day - - 90-day - SOURCE_SUBDIR=sccs_o_197; REPORT_TITLE=OPINION ON Tetrabromophenol Blue, 4,4’-(4,5,6,7-tetrabromo-1,1- dioxido-3H-2,1-benzoxathiol-3-yliden)bis-2,6- dibromophenol (C183); OPINION_NUMBER=SCCS/1573/16; COMMITTEE=Scientific Committee on Consumer Safety (SCCS); REPORT_DATE=16 March 2016; VALUE_TEXT=3; DOSE=Following the dose of 100 mg/kg bw/day changes in urea (males) and cholesterol (females) values were found.; EFFECT=ntial of the test substance. Following the dose of 100 mg/kg bw/day changes in urea (males) and cholesterol (females) values were found. Discolouration of the gastro-intestinal tract was observed and related to the staining properties. No treatment-related changes were observed in organ weights or in the histopathological examination of organs and tissues. The study report authors established a NOAEL of 100 mg/kg bw/day. Due to the ophthalmological and haematological findings at this dose level, the SCCNFP set the NOAEL to 3 mg/kg bw/day. Ref.: 12 Comment The SCCNFP remarked that according to Ref. 15 (Ref. 5 subm. I), a 2% solution of Tetrabromophenol Blue has not been classified as eye irritating and no corneal opacity was observed at this concentration. However, for the highest dose in this 90-day study, 100 mg per kg bw was administered in 5 ml volume per kg, which corresponds to a 2% solution and the observed ophthalmological effects were attributed to direct eye contact. Reassessment by the SCCS In 2004, only a draft stud; CITATION=Ref.: 12 Comment The SCCNFP remarked that according to Ref; CITATION_NUMBERS=[12]; REFERENCE=Ref.: 12 Comment The SCCNFP remarked that according to Ref; DETAILS_JSON={"cas_number":"4430-25-5","citation":"Ref.: 12 Comment The SCCNFP remarked that according to Ref","dose":"Following the dose of 100 mg/kg bw/day changes in urea (males) and cholesterol (females) values were found.","duration":"90-day","effect":"ntial of the test substance. Following the dose of 100 mg/kg bw/day changes in urea (males) and cholesterol (females) values were found. Discolouration of the gastro-intestinal tract was observed and related to the staining properties. No treatment-related changes were observed in organ weights or in the histopathological examination of organs and tissues. The study report authors established a NOAEL of 100 mg/kg bw/day. Due to the ophthalmological and haematological findings at this dose level, the SCCNFP set the NOAEL to 3 mg/kg bw/day. Ref.: 12 Comment The SCCNFP remarked that according to Ref. 15 (Ref. 5 subm. I), a 2% solution of Tetrabromophenol Blue has not been classified as eye irritating and no corneal opacity was observed at this concentration. However, for the highest dose in this 90-day study, 100 mg per kg bw was administered in 5 ml volume per kg, which corresponds to a 2% solution and the observed ophthalmological effects were attributed to direct eye contact. Reassessment by the SCCS In 2004, only a draft stud","endpoint":"","ingredient":"is misleading. The","loael_value":"","noael_unit":"mg/kg bw/day","noael_value":"3","page":23,"route":"","species":"","study_id":"sccs_o_197_noael_002"}
Regulatory source - 5 mg/kg bw/day rat oral - - SOURCE_SUBDIR=sccs_o_197; REPORT_TITLE=OPINION ON Tetrabromophenol Blue, 4,4’-(4,5,6,7-tetrabromo-1,1- dioxido-3H-2,1-benzoxathiol-3-yliden)bis-2,6- dibromophenol (C183); OPINION_NUMBER=SCCS/1573/16; COMMITTEE=Scientific Committee on Consumer Safety (SCCS); REPORT_DATE=16 March 2016; VALUE_TEXT=5; DOSE=Even in the medium dose one foetus with persistent truncus arteriosus was found.; EFFECT=SCCS/1573/16 Opinion on hair dye Tetrabromophenol Blue, 4,4’-(4,5,6,7-tetrabromo-1,1-dioxido-3H-2,1-benzoxathiol-3-yliden)bis- 2,6-dibromophenol (C183) ___________________________________________________________________________________________ 29 attributed to treatment. Even in the medium dose one foetus with persistent truncus arteriosus was found. Conclusion The NOAEL of maternal toxicity was 50 mg/kg bw/day, the NOAEL of teratogenicity was 5 mg/kg bw/day. For embryotoxicity, a NOAEL cannot be established. Ref.: 17 Taken from SCCS/1426/11 Guideline: OECD no. 414 (2001) Species/strain: Rat, strain Wistar rats HanBrl: WIST, outbred (SPF) Group size: 22 mated females per dose group Test item: Tetrabromophenol Blue Batch: TBFB3/02/30 Purity: 98.8 area % (at 615 nm, HPLC) Dose levels: 0, 3, 30 and 300 mg/kg bw/day Vehicle: 5% w/w polyglycol 600, 4% w/w Plantaren 2000 UP (50% aqueous decyl glucoside), 90.5% milli-U water Route: oral, gavage GLP: in compliance Study date 3 January – 20 July 2005 E; CITATION=Ref.: 17 Taken from SCCS/1426/11 Guideline: OECD no; CITATION_NUMBERS=[17,1426,11]; REFERENCE=Ref.: 17 Taken from SCCS/1426/11 Guideline: OECD no; DETAILS_JSON={"cas_number":"4430-25-5","citation":"Ref.: 17 Taken from SCCS/1426/11 Guideline: OECD no","dose":"Even in the medium dose one foetus with persistent truncus arteriosus was found.","duration":"","effect":"SCCS/1573/16 Opinion on hair dye Tetrabromophenol Blue, 4,4’-(4,5,6,7-tetrabromo-1,1-dioxido-3H-2,1-benzoxathiol-3-yliden)bis- 2,6-dibromophenol (C183) ___________________________________________________________________________________________ 29 attributed to treatment. Even in the medium dose one foetus with persistent truncus arteriosus was found. Conclusion The NOAEL of maternal toxicity was 50 mg/kg bw/day, the NOAEL of teratogenicity was 5 mg/kg bw/day. For embryotoxicity, a NOAEL cannot be established. Ref.: 17 Taken from SCCS/1426/11 Guideline: OECD no. 414 (2001) Species/strain: Rat, strain Wistar rats HanBrl: WIST, outbred (SPF) Group size: 22 mated females per dose group Test item: Tetrabromophenol Blue Batch: TBFB3/02/30 Purity: 98.8 area % (at 615 nm, HPLC) Dose levels: 0, 3, 30 and 300 mg/kg bw/day Vehicle: 5% w/w polyglycol 600, 4% w/w Plantaren 2000 UP (50% aqueous decyl glucoside), 90.5% milli-U water Route: oral, gavage GLP: in compliance Study date 3 January – 20 July 2005 E","endpoint":"","ingredient":"is misleading. The","loael_value":"","noael_unit":"mg/kg bw/day","noael_value":"5","page":29,"route":"oral","species":"rat","study_id":"sccs_o_197_noael_009"}
Regulatory source - 30 mg/kg bw/ day rat - - - SOURCE_SUBDIR=sccs_o_197; REPORT_TITLE=OPINION ON Tetrabromophenol Blue, 4,4’-(4,5,6,7-tetrabromo-1,1- dioxido-3H-2,1-benzoxathiol-3-yliden)bis-2,6- dibromophenol (C183); OPINION_NUMBER=SCCS/1573/16; COMMITTEE=Scientific Committee on Consumer Safety (SCCS); REPORT_DATE=16 March 2016; VALUE_TEXT=30; DOSE=incidences of left-sided umbilical arteries and cranially elongated thymuses at the high dose and anophthalmia in the mid-dose group.; EFFECT=incidences of left-sided umbilical arteries and cranially elongated thymuses at the high dose and anophthalmia in the mid-dose group. There was an increased incidence of fused zygomatic arches at the high dose (21 in 12 litters) when compared with the control group (12 in 9 litters). A statistically significant increase in supernumerary rudimentary ribs was observed in the mid and high doses. No changes were noted in the foetuses of the low dose group (3 mg/kg bw). Conclusion Based on these results, the maternal NOAEL was considered to be 30 mg/kg bw/ day. A NOAEL for embryo-foetal effects was derived at 3 mg/kg bw/day. Ref: 18 3.3.9 Toxicokinetics 3.3.9.1 Toxicokinetics in laboratory animals Taken from SCCS/1426/11 Guideline: OECD 417 (1984) and OECD 427 (2004) Species/strain: Rat, Wistar CRL: WI BR (outbreed) (SPF) Group size: Females, mass balance groups (groups 1,2,3,4) 4 per dose; toxicokinetics groups (groups 5, 6, 7, 8) 6 per dose Test substances: Tetrabromophenol Blue-(Phenol-UL-14C) Batch: 064K9418 non-labelled T; CITATION=Ref: 18 3; CITATION_NUMBERS=[18,3]; REFERENCE=Ref: 18 3; DETAILS_JSON={"cas_number":"4430-25-5","citation":"Ref: 18 3","dose":"incidences of left-sided umbilical arteries and cranially elongated thymuses at the high dose and anophthalmia in the mid-dose group.","duration":"","effect":"incidences of left-sided umbilical arteries and cranially elongated thymuses at the high dose and anophthalmia in the mid-dose group. There was an increased incidence of fused zygomatic arches at the high dose (21 in 12 litters) when compared with the control group (12 in 9 litters). A statistically significant increase in supernumerary rudimentary ribs was observed in the mid and high doses. No changes were noted in the foetuses of the low dose group (3 mg/kg bw). Conclusion Based on these results, the maternal NOAEL was considered to be 30 mg/kg bw/ day. A NOAEL for embryo-foetal effects was derived at 3 mg/kg bw/day. Ref: 18 3.3.9 Toxicokinetics 3.3.9.1 Toxicokinetics in laboratory animals Taken from SCCS/1426/11 Guideline: OECD 417 (1984) and OECD 427 (2004) Species/strain: Rat, Wistar CRL: WI BR (outbreed) (SPF) Group size: Females, mass balance groups (groups 1,2,3,4) 4 per dose; toxicokinetics groups (groups 5, 6, 7, 8) 6 per dose Test substances: Tetrabromophenol Blue-(Phenol-UL-14C) Batch: 064K9418 non-labelled T","endpoint":"","ingredient":"is misleading. The","loael_value":"","noael_unit":"mg/kg bw/ day","noael_value":"30","page":30,"route":"","species":"rat","study_id":"sccs_o_197_noael_010"}
Regulatory source - 30 mg/kg bw/ day rat - - - SOURCE_SUBDIR=sccs_o_197; REPORT_TITLE=OPINION ON Tetrabromophenol Blue, 4,4’-(4,5,6,7-tetrabromo-1,1- dioxido-3H-2,1-benzoxathiol-3-yliden)bis-2,6- dibromophenol (C183); OPINION_NUMBER=SCCS/1573/16; COMMITTEE=Scientific Committee on Consumer Safety (SCCS); REPORT_DATE=16 March 2016; VALUE_TEXT=30; DOSE=d cranially elongated thymuses at the high dose and anophthalmia in the mid-dose group.; EFFECT=d cranially elongated thymuses at the high dose and anophthalmia in the mid-dose group. There was an increased incidence of fused zygomatic arches at the high dose (21 in 12 litters) when compared with the control group (12 in 9 litters). A statistically significant increase in supernumerary rudimentary ribs was observed in the mid and high doses. No changes were noted in the foetuses of the low dose group (3 mg/kg bw). Conclusion Based on these results, the maternal NOAEL was considered to be 30 mg/kg bw/ day. A NOAEL for embryo-foetal effects was derived at 3 mg/kg bw/day. Ref: 18 3.3.9 Toxicokinetics 3.3.9.1 Toxicokinetics in laboratory animals Taken from SCCS/1426/11 Guideline: OECD 417 (1984) and OECD 427 (2004) Species/strain: Rat, Wistar CRL: WI BR (outbreed) (SPF) Group size: Females, mass balance groups (groups 1,2,3,4) 4 per dose; toxicokinetics groups (groups 5, 6, 7, 8) 6 per dose Test substances: Tetrabromophenol Blue-(Phenol-UL-14C) Batch: 064K9418 non-labelled Tetrabromophenol Blue Batch: TBFB3/02/30 Purity:; CITATION=Ref: 18 3; CITATION_NUMBERS=[18,3]; REFERENCE=Ref: 18 3; DETAILS_JSON={"cas_number":"4430-25-5","citation":"Ref: 18 3","dose":"d cranially elongated thymuses at the high dose and anophthalmia in the mid-dose group.","duration":"","effect":"d cranially elongated thymuses at the high dose and anophthalmia in the mid-dose group. There was an increased incidence of fused zygomatic arches at the high dose (21 in 12 litters) when compared with the control group (12 in 9 litters). A statistically significant increase in supernumerary rudimentary ribs was observed in the mid and high doses. No changes were noted in the foetuses of the low dose group (3 mg/kg bw). Conclusion Based on these results, the maternal NOAEL was considered to be 30 mg/kg bw/ day. A NOAEL for embryo-foetal effects was derived at 3 mg/kg bw/day. Ref: 18 3.3.9 Toxicokinetics 3.3.9.1 Toxicokinetics in laboratory animals Taken from SCCS/1426/11 Guideline: OECD 417 (1984) and OECD 427 (2004) Species/strain: Rat, Wistar CRL: WI BR (outbreed) (SPF) Group size: Females, mass balance groups (groups 1,2,3,4) 4 per dose; toxicokinetics groups (groups 5, 6, 7, 8) 6 per dose Test substances: Tetrabromophenol Blue-(Phenol-UL-14C) Batch: 064K9418 non-labelled Tetrabromophenol Blue Batch: TBFB3/02/30 Purity:","endpoint":"","ingredient":"is misleading. The","loael_value":"","noael_unit":"mg/kg bw/ day","noael_value":"30","page":30,"route":"","species":"rat","study_id":"sccs_o_197_noael_011"}
Regulatory source - 50 mg/kg bw/day rat - - - SOURCE_SUBDIR=sccs_o_197; REPORT_TITLE=OPINION ON Tetrabromophenol Blue, 4,4’-(4,5,6,7-tetrabromo-1,1- dioxido-3H-2,1-benzoxathiol-3-yliden)bis-2,6- dibromophenol (C183); OPINION_NUMBER=SCCS/1573/16; COMMITTEE=Scientific Committee on Consumer Safety (SCCS); REPORT_DATE=16 March 2016; VALUE_TEXT=50; DOSE=Even in the medium dose one foetus with persistent truncus arteriosus was found.; EFFECT=SCCS/1573/16 Opinion on hair dye Tetrabromophenol Blue, 4,4’-(4,5,6,7-tetrabromo-1,1-dioxido-3H-2,1-benzoxathiol-3-yliden)bis- 2,6-dibromophenol (C183) ___________________________________________________________________________________________ 29 attributed to treatment. Even in the medium dose one foetus with persistent truncus arteriosus was found. Conclusion The NOAEL of maternal toxicity was 50 mg/kg bw/day, the NOAEL of teratogenicity was 5 mg/kg bw/day. For embryotoxicity, a NOAEL cannot be established. Ref.: 17 Taken from SCCS/1426/11 Guideline: OECD no. 414 (2001) Species/strain: Rat, strain Wistar rats HanBrl: WIST, outbred (SPF) Group size: 22 mated females per dose group Test item: Tetrabromophenol Blue Batch: TBFB3/02/30 Purity: 98.8 area % (at 615 nm, HPLC) Dose levels: 0, 3, 30 and 300 mg/kg bw/day Vehicle: 5% w/w polyglycol 600, 4% w/w Plantaren 2000 UP (50% aqueo; CITATION=Ref.: 17 Taken from SCCS/1426/11 Guideline: OECD no; CITATION_NUMBERS=[17,1426,11]; REFERENCE=Ref.: 17 Taken from SCCS/1426/11 Guideline: OECD no; DETAILS_JSON={"cas_number":"4430-25-5","citation":"Ref.: 17 Taken from SCCS/1426/11 Guideline: OECD no","dose":"Even in the medium dose one foetus with persistent truncus arteriosus was found.","duration":"","effect":"SCCS/1573/16 Opinion on hair dye Tetrabromophenol Blue, 4,4’-(4,5,6,7-tetrabromo-1,1-dioxido-3H-2,1-benzoxathiol-3-yliden)bis- 2,6-dibromophenol (C183) ___________________________________________________________________________________________ 29 attributed to treatment. Even in the medium dose one foetus with persistent truncus arteriosus was found. Conclusion The NOAEL of maternal toxicity was 50 mg/kg bw/day, the NOAEL of teratogenicity was 5 mg/kg bw/day. For embryotoxicity, a NOAEL cannot be established. Ref.: 17 Taken from SCCS/1426/11 Guideline: OECD no. 414 (2001) Species/strain: Rat, strain Wistar rats HanBrl: WIST, outbred (SPF) Group size: 22 mated females per dose group Test item: Tetrabromophenol Blue Batch: TBFB3/02/30 Purity: 98.8 area % (at 615 nm, HPLC) Dose levels: 0, 3, 30 and 300 mg/kg bw/day Vehicle: 5% w/w polyglycol 600, 4% w/w Plantaren 2000 UP (50% aqueo","endpoint":"","ingredient":"is misleading. The","loael_value":"","noael_unit":"mg/kg bw/day","noael_value":"50","page":29,"route":"","species":"rat","study_id":"sccs_o_197_noael_008"}
Regulatory source - 100 mg/kg bw/day - - 90-day - SOURCE_SUBDIR=sccs_o_197; REPORT_TITLE=OPINION ON Tetrabromophenol Blue, 4,4’-(4,5,6,7-tetrabromo-1,1- dioxido-3H-2,1-benzoxathiol-3-yliden)bis-2,6- dibromophenol (C183); OPINION_NUMBER=SCCS/1573/16; COMMITTEE=Scientific Committee on Consumer Safety (SCCS); REPORT_DATE=16 March 2016; VALUE_TEXT=100; DOSE=ytes counts observed in males which were statistically significant at 10 and 100 mg/kg bw/day point to a haematotoxic potential of the test substance.; EFFECT=ytes counts observed in males which were statistically significant at 10 and 100 mg/kg bw/day point to a haematotoxic potential of the test substance. Following the dose of 100 mg/kg bw/day changes in urea (males) and cholesterol (females) values were found. Discolouration of the gastro-intestinal tract was observed and related to the staining properties. No treatment-related changes were observed in organ weights or in the histopathological examination of organs and tissues. The study report authors established a NOAEL of 100 mg/kg bw/day. Due to the ophthalmological and haematological findings at this dose level, the SCCNFP set the NOAEL to 3 mg/kg bw/day. Ref.: 12 Comment The SCCNFP remarked that according to Ref. 15 (Ref. 5 subm. I), a 2% solution of Tetrabromophenol Blue has not been classified as eye irritating and no corneal opacity was observed at this concentration. However, for the highest dose in this 90-day study, 100 mg per kg bw was administered in 5 ml volume per kg, which corresponds to a 2% solution and the obs; CITATION=Ref.: 12 Comment The SCCNFP remarked that according to Ref; CITATION_NUMBERS=[12]; REFERENCE=Ref.: 12 Comment The SCCNFP remarked that according to Ref; DETAILS_JSON={"cas_number":"4430-25-5","citation":"Ref.: 12 Comment The SCCNFP remarked that according to Ref","dose":"ytes counts observed in males which were statistically significant at 10 and 100 mg/kg bw/day point to a haematotoxic potential of the test substance.","duration":"90-day","effect":"ytes counts observed in males which were statistically significant at 10 and 100 mg/kg bw/day point to a haematotoxic potential of the test substance. Following the dose of 100 mg/kg bw/day changes in urea (males) and cholesterol (females) values were found. Discolouration of the gastro-intestinal tract was observed and related to the staining properties. No treatment-related changes were observed in organ weights or in the histopathological examination of organs and tissues. The study report authors established a NOAEL of 100 mg/kg bw/day. Due to the ophthalmological and haematological findings at this dose level, the SCCNFP set the NOAEL to 3 mg/kg bw/day. Ref.: 12 Comment The SCCNFP remarked that according to Ref. 15 (Ref. 5 subm. I), a 2% solution of Tetrabromophenol Blue has not been classified as eye irritating and no corneal opacity was observed at this concentration. However, for the highest dose in this 90-day study, 100 mg per kg bw was administered in 5 ml volume per kg, which corresponds to a 2% solution and the obs","endpoint":"","ingredient":"is misleading. The","loael_value":"","noael_unit":"mg/kg bw/day","noael_value":"100","page":23,"route":"","species":"","study_id":"sccs_o_197_noael_001"}
Regulatory source dermal absorption =0.00068 mg/kg bw rat oral 90-day dermal absorption SOURCE_SUBDIR=sccs_o_232; REPORT_TITLE=Final Opinion Version S Scientific Committee on Consumer Safety SCCS OPINION ON Tetrabromophenol Blue, 4,4’-(4,5,6,7-tetrabromo-1,1- dioxido-3H-2,1-benzoxathiol-3-yliden)bis-2,6-; OPINION_NUMBER=SCCS/1610/19; COMMITTEE=Scientific Committee on Consumer Safety (SCCS); REPORT_DATE=final version of 13 December 2019; VALUE_TEXT== 0.00068; DOSE=Opinion on hair dye Tetrabromophenol Blue, 4,4’-(4,5,6,7-tetrabromo-1,1-dioxido-3H-2,1-benzoxathiol-3-yliden)bis- 2,6-dibromophenol (C183) – Submission IV _____________________________________________________________________________________________________________________ 46 Absorption through the skin A = 0.07 µg/cm² Skin Surface Area SSA = 580...; EFFECT=Opinion on hair dye Tetrabromophenol Blue, 4,4’-(4,5,6,7-tetrabromo-1,1-dioxido-3H-2,1-benzoxathiol-3-yliden)bis- 2,6-dibromophenol (C183) – Submission IV _____________________________________________________________________________________________________________________ 46 Absorption through the skin A = 0.07 µg/cm² Skin Surface Area SSA = 580 cm2 Dermal absorption per treatment SSA x A x 0.001 = 0.0406 mg Typical body weight of human = 60 kg Systemic exposure dose (SED) SSA x A x 0.001/60 = 0.00068 mg/kg bw No observed adverse effect level NOAEL = 3 mg/kg bw/d (90-day, oral, rat) Bioavailability 30%* = 0.9 mg/kg bw/d Margin of Safety adjusted NOAEL/SED = 1300 * based on the toxicokinetic study (ref. 21). CALCULATION OF THE MARGIN OF SAFETY (oxidative conditions) (In formulation, on head concentration 0.2%) Absorption through the skin A = 0.04 µg/cm² Skin Surface Area SSA = 580 cm2 Dermal absorption per treatment SSA x A x 0.001 = 0.0232 mg Typical body weight of human = 60 kg Systemic exposure dose (SED) SSA x A x 0.001/60 = 0.00039 mg/kg bw N; CITATION=(ref. 21); CITATION_NUMBERS=[21]; REFERENCE=(ref. 21); DETAILS_JSON={"cas_number":"4430-25-5","citation":"(ref. 21)","dose":"Opinion on hair dye Tetrabromophenol Blue, 4,4’-(4,5,6,7-tetrabromo-1,1-dioxido-3H-2,1-benzoxathiol-3-yliden)bis- 2,6-dibromophenol (C183) – Submission IV _____________________________________________________________________________________________________________________ 46 Absorption through the skin A = 0.07 µg/cm² Skin Surface Area SSA = 580...","duration":"90-day","effect":"Opinion on hair dye Tetrabromophenol Blue, 4,4’-(4,5,6,7-tetrabromo-1,1-dioxido-3H-2,1-benzoxathiol-3-yliden)bis- 2,6-dibromophenol (C183) – Submission IV _____________________________________________________________________________________________________________________ 46 Absorption through the skin A = 0.07 µg/cm² Skin Surface Area SSA = 580 cm2 Dermal absorption per treatment SSA x A x 0.001 = 0.0406 mg Typical body weight of human = 60 kg Systemic exposure dose (SED) SSA x A x 0.001/60 = 0.00068 mg/kg bw No observed adverse effect level NOAEL = 3 mg/kg bw/d (90-day, oral, rat) Bioavailability 30%* = 0.9 mg/kg bw/d Margin of Safety adjusted NOAEL/SED = 1300 * based on the toxicokinetic study (ref. 21). CALCULATION OF THE MARGIN OF SAFETY (oxidative conditions) (In formulation, on head concentration 0.2%) Absorption through the skin A = 0.04 µg/cm² Skin Surface Area SSA = 580 cm2 Dermal absorption per treatment SSA x A x 0.001 = 0.0232 mg Typical body weight of human = 60 kg Systemic exposure dose (SED) SSA x A x 0.001/60 = 0.00039 mg/kg bw N","endpoint":"dermal absorption","ingredient":"Tetrabromophenol Blue","loael_value":"","noael_unit":"mg/kg bw","noael_value":"= 0.00068","page":46,"route":"oral","species":"rat","study_id":"sccs_o_232_noael_014"}
Regulatory source dermal absorption =3 mg/kg bw/d rat oral 90-day dermal absorption SOURCE_SUBDIR=sccs_o_232; REPORT_TITLE=Final Opinion Version S Scientific Committee on Consumer Safety SCCS OPINION ON Tetrabromophenol Blue, 4,4’-(4,5,6,7-tetrabromo-1,1- dioxido-3H-2,1-benzoxathiol-3-yliden)bis-2,6-; OPINION_NUMBER=SCCS/1610/19; COMMITTEE=Scientific Committee on Consumer Safety (SCCS); REPORT_DATE=final version of 13 December 2019; VALUE_TEXT== 3; DOSE=henol Blue, 4,4’-(4,5,6,7-tetrabromo-1,1-dioxido-3H-2,1-benzoxathiol-3-yliden)bis- 2,6-dibromophenol (C183) – Submission IV _____________________________________________________________________________________________________________________ 46 Absorption through the skin A = 0.07 µg/cm² Skin Surface Area SSA = 580 cm2 Dermal absorption per trea...; EFFECT=henol Blue, 4,4’-(4,5,6,7-tetrabromo-1,1-dioxido-3H-2,1-benzoxathiol-3-yliden)bis- 2,6-dibromophenol (C183) – Submission IV _____________________________________________________________________________________________________________________ 46 Absorption through the skin A = 0.07 µg/cm² Skin Surface Area SSA = 580 cm2 Dermal absorption per treatment SSA x A x 0.001 = 0.0406 mg Typical body weight of human = 60 kg Systemic exposure dose (SED) SSA x A x 0.001/60 = 0.00068 mg/kg bw No observed adverse effect level NOAEL = 3 mg/kg bw/d (90-day, oral, rat) Bioavailability 30%* = 0.9 mg/kg bw/d Margin of Safety adjusted NOAEL/SED = 1300 * based on the toxicokinetic study (ref. 21). CALCULATION OF THE MARGIN OF SAFETY (oxidative conditions) (In formulation, on head concentration 0.2%) Absorption through the skin A = 0.04 µg/cm² Skin Surface Area SSA = 580 cm2 Dermal absorption per treatment SSA x A x 0.001 = 0.0232 mg Typical body weight of human = 60 kg Systemic exposure dose (SED) SSA x A x 0.001/60 = 0.00039 mg/kg bw No obse; CITATION=(ref. 21); CITATION_NUMBERS=[21]; REFERENCE=(ref. 21); DETAILS_JSON={"cas_number":"4430-25-5","citation":"(ref. 21)","dose":"henol Blue, 4,4’-(4,5,6,7-tetrabromo-1,1-dioxido-3H-2,1-benzoxathiol-3-yliden)bis- 2,6-dibromophenol (C183) – Submission IV _____________________________________________________________________________________________________________________ 46 Absorption through the skin A = 0.07 µg/cm² Skin Surface Area SSA = 580 cm2 Dermal absorption per trea...","duration":"90-day","effect":"henol Blue, 4,4’-(4,5,6,7-tetrabromo-1,1-dioxido-3H-2,1-benzoxathiol-3-yliden)bis- 2,6-dibromophenol (C183) – Submission IV _____________________________________________________________________________________________________________________ 46 Absorption through the skin A = 0.07 µg/cm² Skin Surface Area SSA = 580 cm2 Dermal absorption per treatment SSA x A x 0.001 = 0.0406 mg Typical body weight of human = 60 kg Systemic exposure dose (SED) SSA x A x 0.001/60 = 0.00068 mg/kg bw No observed adverse effect level NOAEL = 3 mg/kg bw/d (90-day, oral, rat) Bioavailability 30%* = 0.9 mg/kg bw/d Margin of Safety adjusted NOAEL/SED = 1300 * based on the toxicokinetic study (ref. 21). CALCULATION OF THE MARGIN OF SAFETY (oxidative conditions) (In formulation, on head concentration 0.2%) Absorption through the skin A = 0.04 µg/cm² Skin Surface Area SSA = 580 cm2 Dermal absorption per treatment SSA x A x 0.001 = 0.0232 mg Typical body weight of human = 60 kg Systemic exposure dose (SED) SSA x A x 0.001/60 = 0.00039 mg/kg bw No obse","endpoint":"dermal absorption","ingredient":"Tetrabromophenol Blue","loael_value":"","noael_unit":"mg/kg bw/d","noael_value":"= 3","page":46,"route":"oral","species":"rat","study_id":"sccs_o_232_noael_015"}
Regulatory source dermal absorption =0.9 mg/kg bw/d rat oral 90-day dermal absorption SOURCE_SUBDIR=sccs_o_232; REPORT_TITLE=Final Opinion Version S Scientific Committee on Consumer Safety SCCS OPINION ON Tetrabromophenol Blue, 4,4’-(4,5,6,7-tetrabromo-1,1- dioxido-3H-2,1-benzoxathiol-3-yliden)bis-2,6-; OPINION_NUMBER=SCCS/1610/19; COMMITTEE=Scientific Committee on Consumer Safety (SCCS); REPORT_DATE=final version of 13 December 2019; VALUE_TEXT== 0.9; DOSE=3) – Submission IV _____________________________________________________________________________________________________________________ 46 Absorption through the skin A = 0.07 µg/cm² Skin Surface Area SSA = 580 cm2 Dermal absorption per treatment SSA x A x 0.001 = 0.0406 mg Typical body weight of human = 60 kg Systemic exposure dose (SED) SSA x...; EFFECT=3) – Submission IV _____________________________________________________________________________________________________________________ 46 Absorption through the skin A = 0.07 µg/cm² Skin Surface Area SSA = 580 cm2 Dermal absorption per treatment SSA x A x 0.001 = 0.0406 mg Typical body weight of human = 60 kg Systemic exposure dose (SED) SSA x A x 0.001/60 = 0.00068 mg/kg bw No observed adverse effect level NOAEL = 3 mg/kg bw/d (90-day, oral, rat) Bioavailability 30%* = 0.9 mg/kg bw/d Margin of Safety adjusted NOAEL/SED = 1300 * based on the toxicokinetic study (ref. 21). CALCULATION OF THE MARGIN OF SAFETY (oxidative conditions) (In formulation, on head concentration 0.2%) Absorption through the skin A = 0.04 µg/cm² Skin Surface Area SSA = 580 cm2 Dermal absorption per treatment SSA x A x 0.001 = 0.0232 mg Typical body weight of human = 60 kg Systemic exposure dose (SED) SSA x A x 0.001/60 = 0.00039 mg/kg bw No observed adverse effect level NOAEL = 3 mg/kg bw/d (90-day, oral, rat) Bioavailability 30%* = 0.9 mg/kg bw/d; CITATION=(ref. 21); CITATION_NUMBERS=[21]; REFERENCE=(ref. 21); DETAILS_JSON={"cas_number":"4430-25-5","citation":"(ref. 21)","dose":"3) – Submission IV _____________________________________________________________________________________________________________________ 46 Absorption through the skin A = 0.07 µg/cm² Skin Surface Area SSA = 580 cm2 Dermal absorption per treatment SSA x A x 0.001 = 0.0406 mg Typical body weight of human = 60 kg Systemic exposure dose (SED) SSA x...","duration":"90-day","effect":"3) – Submission IV _____________________________________________________________________________________________________________________ 46 Absorption through the skin A = 0.07 µg/cm² Skin Surface Area SSA = 580 cm2 Dermal absorption per treatment SSA x A x 0.001 = 0.0406 mg Typical body weight of human = 60 kg Systemic exposure dose (SED) SSA x A x 0.001/60 = 0.00068 mg/kg bw No observed adverse effect level NOAEL = 3 mg/kg bw/d (90-day, oral, rat) Bioavailability 30%* = 0.9 mg/kg bw/d Margin of Safety adjusted NOAEL/SED = 1300 * based on the toxicokinetic study (ref. 21). CALCULATION OF THE MARGIN OF SAFETY (oxidative conditions) (In formulation, on head concentration 0.2%) Absorption through the skin A = 0.04 µg/cm² Skin Surface Area SSA = 580 cm2 Dermal absorption per treatment SSA x A x 0.001 = 0.0232 mg Typical body weight of human = 60 kg Systemic exposure dose (SED) SSA x A x 0.001/60 = 0.00039 mg/kg bw No observed adverse effect level NOAEL = 3 mg/kg bw/d (90-day, oral, rat) Bioavailability 30%* = 0.9 mg/kg bw/d","endpoint":"dermal absorption","ingredient":"Tetrabromophenol Blue","loael_value":"","noael_unit":"mg/kg bw/d","noael_value":"= 0.9","page":46,"route":"oral","species":"rat","study_id":"sccs_o_232_noael_016"}
Regulatory source dermal absorption =0.00039 mg/kg bw rat oral 90-day dermal absorption SOURCE_SUBDIR=sccs_o_232; REPORT_TITLE=Final Opinion Version S Scientific Committee on Consumer Safety SCCS OPINION ON Tetrabromophenol Blue, 4,4’-(4,5,6,7-tetrabromo-1,1- dioxido-3H-2,1-benzoxathiol-3-yliden)bis-2,6-; OPINION_NUMBER=SCCS/1610/19; COMMITTEE=Scientific Committee on Consumer Safety (SCCS); REPORT_DATE=final version of 13 December 2019; VALUE_TEXT== 0.00039; DOSE=l NOAEL = 3 mg/kg bw/d (90-day, oral, rat) Bioavailability 30%* = 0.9 mg/kg bw/d Margin of Safety adjusted NOAEL/SED = 1300 * based on the toxicokinetic study (ref.; EFFECT=l NOAEL = 3 mg/kg bw/d (90-day, oral, rat) Bioavailability 30%* = 0.9 mg/kg bw/d Margin of Safety adjusted NOAEL/SED = 1300 * based on the toxicokinetic study (ref. 21). CALCULATION OF THE MARGIN OF SAFETY (oxidative conditions) (In formulation, on head concentration 0.2%) Absorption through the skin A = 0.04 µg/cm² Skin Surface Area SSA = 580 cm2 Dermal absorption per treatment SSA x A x 0.001 = 0.0232 mg Typical body weight of human = 60 kg Systemic exposure dose (SED) SSA x A x 0.001/60 = 0.00039 mg/kg bw No observed adverse effect level NOAEL = 3 mg/kg bw/d (90-day, oral, rat) Bioavailability 30%* = 0.9 mg/kg bw/d Margin of Safety adjusted NOAEL/SED = 2300 * based on the toxicokinetic study (ref. 21). The above MoS calculations only refer to batch TBFB3/02/30 that was used for the toxicity tests, not the current market quality batches. Because of the large margins of safety (1,300 for non-oxidative conditions and 2,300 for non-oxidative conditions) calculated for the batch TBFB3/02/30, the SCCS has considered that around 2.5 fold relative inc; CITATION=(ref. 21); CITATION_NUMBERS=[21]; REFERENCE=(ref. 21); DETAILS_JSON={"cas_number":"4430-25-5","citation":"(ref. 21)","dose":"l NOAEL = 3 mg/kg bw/d (90-day, oral, rat) Bioavailability 30%* = 0.9 mg/kg bw/d Margin of Safety adjusted NOAEL/SED = 1300 * based on the toxicokinetic study (ref.","duration":"90-day","effect":"l NOAEL = 3 mg/kg bw/d (90-day, oral, rat) Bioavailability 30%* = 0.9 mg/kg bw/d Margin of Safety adjusted NOAEL/SED = 1300 * based on the toxicokinetic study (ref. 21). CALCULATION OF THE MARGIN OF SAFETY (oxidative conditions) (In formulation, on head concentration 0.2%) Absorption through the skin A = 0.04 µg/cm² Skin Surface Area SSA = 580 cm2 Dermal absorption per treatment SSA x A x 0.001 = 0.0232 mg Typical body weight of human = 60 kg Systemic exposure dose (SED) SSA x A x 0.001/60 = 0.00039 mg/kg bw No observed adverse effect level NOAEL = 3 mg/kg bw/d (90-day, oral, rat) Bioavailability 30%* = 0.9 mg/kg bw/d Margin of Safety adjusted NOAEL/SED = 2300 * based on the toxicokinetic study (ref. 21). The above MoS calculations only refer to batch TBFB3/02/30 that was used for the toxicity tests, not the current market quality batches. Because of the large margins of safety (1,300 for non-oxidative conditions and 2,300 for non-oxidative conditions) calculated for the batch TBFB3/02/30, the SCCS has considered that around 2.5 fold relative inc","endpoint":"dermal absorption","ingredient":"Tetrabromophenol Blue","loael_value":"","noael_unit":"mg/kg bw","noael_value":"= 0.00039","page":46,"route":"oral","species":"rat","study_id":"sccs_o_232_noael_017"}
Regulatory source dermal absorption =3 mg/kg bw/d rat oral 90-day dermal absorption SOURCE_SUBDIR=sccs_o_232; REPORT_TITLE=Final Opinion Version S Scientific Committee on Consumer Safety SCCS OPINION ON Tetrabromophenol Blue, 4,4’-(4,5,6,7-tetrabromo-1,1- dioxido-3H-2,1-benzoxathiol-3-yliden)bis-2,6-; OPINION_NUMBER=SCCS/1610/19; COMMITTEE=Scientific Committee on Consumer Safety (SCCS); REPORT_DATE=final version of 13 December 2019; VALUE_TEXT== 3; DOSE=ral, rat) Bioavailability 30%* = 0.9 mg/kg bw/d Margin of Safety adjusted NOAEL/SED = 1300 * based on the toxicokinetic study (ref.; EFFECT=ral, rat) Bioavailability 30%* = 0.9 mg/kg bw/d Margin of Safety adjusted NOAEL/SED = 1300 * based on the toxicokinetic study (ref. 21). CALCULATION OF THE MARGIN OF SAFETY (oxidative conditions) (In formulation, on head concentration 0.2%) Absorption through the skin A = 0.04 µg/cm² Skin Surface Area SSA = 580 cm2 Dermal absorption per treatment SSA x A x 0.001 = 0.0232 mg Typical body weight of human = 60 kg Systemic exposure dose (SED) SSA x A x 0.001/60 = 0.00039 mg/kg bw No observed adverse effect level NOAEL = 3 mg/kg bw/d (90-day, oral, rat) Bioavailability 30%* = 0.9 mg/kg bw/d Margin of Safety adjusted NOAEL/SED = 2300 * based on the toxicokinetic study (ref. 21). The above MoS calculations only refer to batch TBFB3/02/30 that was used for the toxicity tests, not the current market quality batches. Because of the large margins of safety (1,300 for non-oxidative conditions and 2,300 for non-oxidative conditions) calculated for the batch TBFB3/02/30, the SCCS has considered that around 2.5 fold relative increase; CITATION=(ref. 21); CITATION_NUMBERS=[21]; REFERENCE=(ref. 21); DETAILS_JSON={"cas_number":"4430-25-5","citation":"(ref. 21)","dose":"ral, rat) Bioavailability 30%* = 0.9 mg/kg bw/d Margin of Safety adjusted NOAEL/SED = 1300 * based on the toxicokinetic study (ref.","duration":"90-day","effect":"ral, rat) Bioavailability 30%* = 0.9 mg/kg bw/d Margin of Safety adjusted NOAEL/SED = 1300 * based on the toxicokinetic study (ref. 21). CALCULATION OF THE MARGIN OF SAFETY (oxidative conditions) (In formulation, on head concentration 0.2%) Absorption through the skin A = 0.04 µg/cm² Skin Surface Area SSA = 580 cm2 Dermal absorption per treatment SSA x A x 0.001 = 0.0232 mg Typical body weight of human = 60 kg Systemic exposure dose (SED) SSA x A x 0.001/60 = 0.00039 mg/kg bw No observed adverse effect level NOAEL = 3 mg/kg bw/d (90-day, oral, rat) Bioavailability 30%* = 0.9 mg/kg bw/d Margin of Safety adjusted NOAEL/SED = 2300 * based on the toxicokinetic study (ref. 21). The above MoS calculations only refer to batch TBFB3/02/30 that was used for the toxicity tests, not the current market quality batches. Because of the large margins of safety (1,300 for non-oxidative conditions and 2,300 for non-oxidative conditions) calculated for the batch TBFB3/02/30, the SCCS has considered that around 2.5 fold relative increase","endpoint":"dermal absorption","ingredient":"Tetrabromophenol Blue","loael_value":"","noael_unit":"mg/kg bw/d","noael_value":"= 3","page":46,"route":"oral","species":"rat","study_id":"sccs_o_232_noael_018"}
Regulatory source dermal absorption =0.9 mg/kg bw/d rat oral 90-day dermal absorption SOURCE_SUBDIR=sccs_o_232; REPORT_TITLE=Final Opinion Version S Scientific Committee on Consumer Safety SCCS OPINION ON Tetrabromophenol Blue, 4,4’-(4,5,6,7-tetrabromo-1,1- dioxido-3H-2,1-benzoxathiol-3-yliden)bis-2,6-; OPINION_NUMBER=SCCS/1610/19; COMMITTEE=Scientific Committee on Consumer Safety (SCCS); REPORT_DATE=final version of 13 December 2019; VALUE_TEXT== 0.9; DOSE=CALCULATION OF THE MARGIN OF SAFETY (oxidative conditions) (In formulation, on head concentration 0.2%) Absorption through the skin A = 0.04 µg/cm² Skin Surface Area SSA = 580 cm2 Dermal absorption per treatment SSA x A x 0.001 = 0.0232 mg Typical body weight of human = 60 kg Systemic exposure dose (SED) SSA x A x 0.001/60 = 0.00039 mg/kg bw No...; EFFECT=oxicokinetic study (ref. 21). CALCULATION OF THE MARGIN OF SAFETY (oxidative conditions) (In formulation, on head concentration 0.2%) Absorption through the skin A = 0.04 µg/cm² Skin Surface Area SSA = 580 cm2 Dermal absorption per treatment SSA x A x 0.001 = 0.0232 mg Typical body weight of human = 60 kg Systemic exposure dose (SED) SSA x A x 0.001/60 = 0.00039 mg/kg bw No observed adverse effect level NOAEL = 3 mg/kg bw/d (90-day, oral, rat) Bioavailability 30%* = 0.9 mg/kg bw/d Margin of Safety adjusted NOAEL/SED = 2300 * based on the toxicokinetic study (ref. 21). The above MoS calculations only refer to batch TBFB3/02/30 that was used for the toxicity tests, not the current market quality batches. Because of the large margins of safety (1,300 for non-oxidative conditions and 2,300 for non-oxidative conditions) calculated for the batch TBFB3/02/30, the SCCS has considered that around 2.5 fold relative increase in the proportion of the two homologues (4 and 5 in Table 2) in batch 7215600060 is not likely to influence; CITATION=(ref. 21); CITATION_NUMBERS=[21]; REFERENCE=(ref. 21); DETAILS_JSON={"cas_number":"4430-25-5","citation":"(ref. 21)","dose":"CALCULATION OF THE MARGIN OF SAFETY (oxidative conditions) (In formulation, on head concentration 0.2%) Absorption through the skin A = 0.04 µg/cm² Skin Surface Area SSA = 580 cm2 Dermal absorption per treatment SSA x A x 0.001 = 0.0232 mg Typical body weight of human = 60 kg Systemic exposure dose (SED) SSA x A x 0.001/60 = 0.00039 mg/kg bw No...","duration":"90-day","effect":"oxicokinetic study (ref. 21). CALCULATION OF THE MARGIN OF SAFETY (oxidative conditions) (In formulation, on head concentration 0.2%) Absorption through the skin A = 0.04 µg/cm² Skin Surface Area SSA = 580 cm2 Dermal absorption per treatment SSA x A x 0.001 = 0.0232 mg Typical body weight of human = 60 kg Systemic exposure dose (SED) SSA x A x 0.001/60 = 0.00039 mg/kg bw No observed adverse effect level NOAEL = 3 mg/kg bw/d (90-day, oral, rat) Bioavailability 30%* = 0.9 mg/kg bw/d Margin of Safety adjusted NOAEL/SED = 2300 * based on the toxicokinetic study (ref. 21). The above MoS calculations only refer to batch TBFB3/02/30 that was used for the toxicity tests, not the current market quality batches. Because of the large margins of safety (1,300 for non-oxidative conditions and 2,300 for non-oxidative conditions) calculated for the batch TBFB3/02/30, the SCCS has considered that around 2.5 fold relative increase in the proportion of the two homologues (4 and 5 in Table 2) in batch 7215600060 is not likely to influence","endpoint":"dermal absorption","ingredient":"Tetrabromophenol Blue","loael_value":"","noael_unit":"mg/kg bw/d","noael_value":"= 0.9","page":46,"route":"oral","species":"rat","study_id":"sccs_o_232_noael_019"}
Regulatory source dermal absorption =0.00039 mg/kg bw rat oral 90-day dermal absorption SOURCE_SUBDIR=sccs_o_197; REPORT_TITLE=OPINION ON Tetrabromophenol Blue, 4,4’-(4,5,6,7-tetrabromo-1,1- dioxido-3H-2,1-benzoxathiol-3-yliden)bis-2,6- dibromophenol (C183); OPINION_NUMBER=SCCS/1573/16; COMMITTEE=Scientific Committee on Consumer Safety (SCCS); REPORT_DATE=16 March 2016; VALUE_TEXT== 0.00039; DOSE=l NOAEL = 3 mg/kg bw/d (90-day, oral, rat) Bioavailability 30%* = 0.9 mg/kg bw/d Margin of Safety adjusted NOAEL/SED = 1300 * based on the toxicokinetic study (ref.; EFFECT=l NOAEL = 3 mg/kg bw/d (90-day, oral, rat) Bioavailability 30%* = 0.9 mg/kg bw/d Margin of Safety adjusted NOAEL/SED = 1300 * based on the toxicokinetic study (ref. 21). CALCULATION OF THE MARGIN OF SAFETY (oxidative conditions) (In formulation, on head concentration 0.2%) Absorption through the skin A = 0.04 µg/cm² Skin Area surface SAS = 580 cm2 Dermal absorption per treatment SAS x A x 0.001 = 0.0232 mg Typical body weight of human = 60 kg Systemic exposure dose (SED) SAS x A x 0.001/… = 0.00039 mg/kg bw No observed adverse effect level NOAEL = 3 mg/kg bw/d (90-day, oral, rat) Bioavailability 30%* = 0.9 mg/kg bw/d Margin of Safety adjusted NOAEL/SED = 2300 * based on the toxicokinetic study (ref. 21). 3.3.14 Discussion Physicochemical properties Tetrabromophenol Blue is used in oxidative- as well as in non-oxidative hair dye formulations at a maximum concentration of 0.2% on the scalp. The test material is not composed of a single substance. Although the main component is octabromo derivative of phenolsulfonphthalein, the material also conta; CITATION=(ref. 21); CITATION_NUMBERS=[21]; REFERENCE=(ref. 21); DETAILS_JSON={"cas_number":"4430-25-5","citation":"(ref. 21)","dose":"l NOAEL = 3 mg/kg bw/d (90-day, oral, rat) Bioavailability 30%* = 0.9 mg/kg bw/d Margin of Safety adjusted NOAEL/SED = 1300 * based on the toxicokinetic study (ref.","duration":"90-day","effect":"l NOAEL = 3 mg/kg bw/d (90-day, oral, rat) Bioavailability 30%* = 0.9 mg/kg bw/d Margin of Safety adjusted NOAEL/SED = 1300 * based on the toxicokinetic study (ref. 21). CALCULATION OF THE MARGIN OF SAFETY (oxidative conditions) (In formulation, on head concentration 0.2%) Absorption through the skin A = 0.04 µg/cm² Skin Area surface SAS = 580 cm2 Dermal absorption per treatment SAS x A x 0.001 = 0.0232 mg Typical body weight of human = 60 kg Systemic exposure dose (SED) SAS x A x 0.001/… = 0.00039 mg/kg bw No observed adverse effect level NOAEL = 3 mg/kg bw/d (90-day, oral, rat) Bioavailability 30%* = 0.9 mg/kg bw/d Margin of Safety adjusted NOAEL/SED = 2300 * based on the toxicokinetic study (ref. 21). 3.3.14 Discussion Physicochemical properties Tetrabromophenol Blue is used in oxidative- as well as in non-oxidative hair dye formulations at a maximum concentration of 0.2% on the scalp. The test material is not composed of a single substance. Although the main component is octabromo derivative of phenolsulfonphthalein, the material also conta","endpoint":"dermal absorption","ingredient":"is misleading. The","loael_value":"","noael_unit":"mg/kg bw","noael_value":"= 0.00039","page":34,"route":"oral","species":"rat","study_id":"sccs_o_197_noael_015"}
Regulatory source dermal absorption =0.00068 mg/kg bw rat oral 90-day dermal absorption SOURCE_SUBDIR=sccs_o_197; REPORT_TITLE=OPINION ON Tetrabromophenol Blue, 4,4’-(4,5,6,7-tetrabromo-1,1- dioxido-3H-2,1-benzoxathiol-3-yliden)bis-2,6- dibromophenol (C183); OPINION_NUMBER=SCCS/1573/16; COMMITTEE=Scientific Committee on Consumer Safety (SCCS); REPORT_DATE=16 March 2016; VALUE_TEXT== 0.00068; DOSE=o-1,1-dioxido-3H-2,1-benzoxathiol-3-yliden)bis- 2,6-dibromophenol (C183) ___________________________________________________________________________________________ 34 CALCULATION OF THE MARGIN OF SAFETY (non-oxidative conditions) (In formulation, on head concentration 0.2%) Absorption through the skin A = 0.07 µg/cm² Skin Area surface SAS = 580...; EFFECT=o-1,1-dioxido-3H-2,1-benzoxathiol-3-yliden)bis- 2,6-dibromophenol (C183) ___________________________________________________________________________________________ 34 CALCULATION OF THE MARGIN OF SAFETY (non-oxidative conditions) (In formulation, on head concentration 0.2%) Absorption through the skin A = 0.07 µg/cm² Skin Area surface SAS = 580 cm2 Dermal absorption per treatment SAS x A x 0.001 = 0.0406 mg Typical body weight of human = 60 kg Systemic exposure dose (SED) SAS x A x 0.001/… = 0.00068 mg/kg bw No observed adverse effect level NOAEL = 3 mg/kg bw/d (90-day, oral, rat) Bioavailability 30%* = 0.9 mg/kg bw/d Margin of Safety adjusted NOAEL/SED = 1300 * based on the toxicokinetic study (ref. 21). CALCULATION OF THE MARGIN OF SAFETY (oxidative conditions) (In formulation, on head concentration 0.2%) Absorption through the skin A = 0.04 µg/cm² Skin Area surface SAS = 580 cm2 Dermal absorption per treatment SAS x A x 0.001 = 0.0232 mg Typical body weight of human = 60 kg Systemic exposure dose (SED) SAS x A x 0.001/… = 0.00039 mg/kg bw N; CITATION=(ref. 21); CITATION_NUMBERS=[21]; REFERENCE=(ref. 21); DETAILS_JSON={"cas_number":"4430-25-5","citation":"(ref. 21)","dose":"o-1,1-dioxido-3H-2,1-benzoxathiol-3-yliden)bis- 2,6-dibromophenol (C183) ___________________________________________________________________________________________ 34 CALCULATION OF THE MARGIN OF SAFETY (non-oxidative conditions) (In formulation, on head concentration 0.2%) Absorption through the skin A = 0.07 µg/cm² Skin Area surface SAS = 580...","duration":"90-day","effect":"o-1,1-dioxido-3H-2,1-benzoxathiol-3-yliden)bis- 2,6-dibromophenol (C183) ___________________________________________________________________________________________ 34 CALCULATION OF THE MARGIN OF SAFETY (non-oxidative conditions) (In formulation, on head concentration 0.2%) Absorption through the skin A = 0.07 µg/cm² Skin Area surface SAS = 580 cm2 Dermal absorption per treatment SAS x A x 0.001 = 0.0406 mg Typical body weight of human = 60 kg Systemic exposure dose (SED) SAS x A x 0.001/… = 0.00068 mg/kg bw No observed adverse effect level NOAEL = 3 mg/kg bw/d (90-day, oral, rat) Bioavailability 30%* = 0.9 mg/kg bw/d Margin of Safety adjusted NOAEL/SED = 1300 * based on the toxicokinetic study (ref. 21). CALCULATION OF THE MARGIN OF SAFETY (oxidative conditions) (In formulation, on head concentration 0.2%) Absorption through the skin A = 0.04 µg/cm² Skin Area surface SAS = 580 cm2 Dermal absorption per treatment SAS x A x 0.001 = 0.0232 mg Typical body weight of human = 60 kg Systemic exposure dose (SED) SAS x A x 0.001/… = 0.00039 mg/kg bw N","endpoint":"dermal absorption","ingredient":"is misleading. The","loael_value":"","noael_unit":"mg/kg bw","noael_value":"= 0.00068","page":34,"route":"oral","species":"rat","study_id":"sccs_o_197_noael_012"}
Regulatory source dermal absorption =0.9 mg/kg bw/d rat oral 90-day dermal absorption SOURCE_SUBDIR=sccs_o_197; REPORT_TITLE=OPINION ON Tetrabromophenol Blue, 4,4’-(4,5,6,7-tetrabromo-1,1- dioxido-3H-2,1-benzoxathiol-3-yliden)bis-2,6- dibromophenol (C183); OPINION_NUMBER=SCCS/1573/16; COMMITTEE=Scientific Committee on Consumer Safety (SCCS); REPORT_DATE=16 March 2016; VALUE_TEXT== 0.9; DOSE=_________________________ 34 CALCULATION OF THE MARGIN OF SAFETY (non-oxidative conditions) (In formulation, on head concentration 0.2%) Absorption through the skin A = 0.07 µg/cm² Skin Area surface SAS = 580 cm2 Dermal absorption per treatment SAS x A x 0.001 = 0.0406 mg Typical body weight of human = 60 kg Systemic exposure dose (SED) SAS x A...; EFFECT=_________________________ 34 CALCULATION OF THE MARGIN OF SAFETY (non-oxidative conditions) (In formulation, on head concentration 0.2%) Absorption through the skin A = 0.07 µg/cm² Skin Area surface SAS = 580 cm2 Dermal absorption per treatment SAS x A x 0.001 = 0.0406 mg Typical body weight of human = 60 kg Systemic exposure dose (SED) SAS x A x 0.001/… = 0.00068 mg/kg bw No observed adverse effect level NOAEL = 3 mg/kg bw/d (90-day, oral, rat) Bioavailability 30%* = 0.9 mg/kg bw/d Margin of Safety adjusted NOAEL/SED = 1300 * based on the toxicokinetic study (ref. 21). CALCULATION OF THE MARGIN OF SAFETY (oxidative conditions) (In formulation, on head concentration 0.2%) Absorption through the skin A = 0.04 µg/cm² Skin Area surface SAS = 580 cm2 Dermal absorption per treatment SAS x A x 0.001 = 0.0232 mg Typical body weight of human = 60 kg Systemic exposure dose (SED) SAS x A x 0.001/… = 0.00039 mg/kg bw No observed adverse effect level NOAEL = 3 mg/kg bw/d (90-day, oral, rat) Bioavailability 30%* = 0.9 mg/kg bw/d; CITATION=(ref. 21); CITATION_NUMBERS=[21]; REFERENCE=(ref. 21); DETAILS_JSON={"cas_number":"4430-25-5","citation":"(ref. 21)","dose":"_________________________ 34 CALCULATION OF THE MARGIN OF SAFETY (non-oxidative conditions) (In formulation, on head concentration 0.2%) Absorption through the skin A = 0.07 µg/cm² Skin Area surface SAS = 580 cm2 Dermal absorption per treatment SAS x A x 0.001 = 0.0406 mg Typical body weight of human = 60 kg Systemic exposure dose (SED) SAS x A...","duration":"90-day","effect":"_________________________ 34 CALCULATION OF THE MARGIN OF SAFETY (non-oxidative conditions) (In formulation, on head concentration 0.2%) Absorption through the skin A = 0.07 µg/cm² Skin Area surface SAS = 580 cm2 Dermal absorption per treatment SAS x A x 0.001 = 0.0406 mg Typical body weight of human = 60 kg Systemic exposure dose (SED) SAS x A x 0.001/… = 0.00068 mg/kg bw No observed adverse effect level NOAEL = 3 mg/kg bw/d (90-day, oral, rat) Bioavailability 30%* = 0.9 mg/kg bw/d Margin of Safety adjusted NOAEL/SED = 1300 * based on the toxicokinetic study (ref. 21). CALCULATION OF THE MARGIN OF SAFETY (oxidative conditions) (In formulation, on head concentration 0.2%) Absorption through the skin A = 0.04 µg/cm² Skin Area surface SAS = 580 cm2 Dermal absorption per treatment SAS x A x 0.001 = 0.0232 mg Typical body weight of human = 60 kg Systemic exposure dose (SED) SAS x A x 0.001/… = 0.00039 mg/kg bw No observed adverse effect level NOAEL = 3 mg/kg bw/d (90-day, oral, rat) Bioavailability 30%* = 0.9 mg/kg bw/d","endpoint":"dermal absorption","ingredient":"is misleading. The","loael_value":"","noael_unit":"mg/kg bw/d","noael_value":"= 0.9","page":34,"route":"oral","species":"rat","study_id":"sccs_o_197_noael_014"}
Regulatory source dermal absorption =0.9 mg/kg bw/d rat oral 90-day dermal absorption SOURCE_SUBDIR=sccs_o_197; REPORT_TITLE=OPINION ON Tetrabromophenol Blue, 4,4’-(4,5,6,7-tetrabromo-1,1- dioxido-3H-2,1-benzoxathiol-3-yliden)bis-2,6- dibromophenol (C183); OPINION_NUMBER=SCCS/1573/16; COMMITTEE=Scientific Committee on Consumer Safety (SCCS); REPORT_DATE=16 March 2016; VALUE_TEXT== 0.9; DOSE=CALCULATION OF THE MARGIN OF SAFETY (oxidative conditions) (In formulation, on head concentration 0.2%) Absorption through the skin A = 0.04 µg/cm² Skin Area surface SAS = 580 cm2 Dermal absorption per treatment SAS x A x 0.001 = 0.0232 mg Typical body weight of human = 60 kg Systemic exposure dose (SED) SAS x A x 0.001/… = 0.00039 mg/kg bw No o...; EFFECT=toxicokinetic study (ref. 21). CALCULATION OF THE MARGIN OF SAFETY (oxidative conditions) (In formulation, on head concentration 0.2%) Absorption through the skin A = 0.04 µg/cm² Skin Area surface SAS = 580 cm2 Dermal absorption per treatment SAS x A x 0.001 = 0.0232 mg Typical body weight of human = 60 kg Systemic exposure dose (SED) SAS x A x 0.001/… = 0.00039 mg/kg bw No observed adverse effect level NOAEL = 3 mg/kg bw/d (90-day, oral, rat) Bioavailability 30%* = 0.9 mg/kg bw/d Margin of Safety adjusted NOAEL/SED = 2300 * based on the toxicokinetic study (ref. 21). 3.3.14 Discussion Physicochemical properties Tetrabromophenol Blue is used in oxidative- as well as in non-oxidative hair dye formulations at a maximum concentration of 0.2% on the scalp. The test material is not composed of a single substance. Although the main component is octabromo derivative of phenolsulfonphthalein, the material also contains heptabromo- and hexabromo- homologues. Analysis of different batches shows a large variation in composition o; CITATION=(ref. 21); CITATION_NUMBERS=[21]; REFERENCE=(ref. 21); DETAILS_JSON={"cas_number":"4430-25-5","citation":"(ref. 21)","dose":"CALCULATION OF THE MARGIN OF SAFETY (oxidative conditions) (In formulation, on head concentration 0.2%) Absorption through the skin A = 0.04 µg/cm² Skin Area surface SAS = 580 cm2 Dermal absorption per treatment SAS x A x 0.001 = 0.0232 mg Typical body weight of human = 60 kg Systemic exposure dose (SED) SAS x A x 0.001/… = 0.00039 mg/kg bw No o...","duration":"90-day","effect":"toxicokinetic study (ref. 21). CALCULATION OF THE MARGIN OF SAFETY (oxidative conditions) (In formulation, on head concentration 0.2%) Absorption through the skin A = 0.04 µg/cm² Skin Area surface SAS = 580 cm2 Dermal absorption per treatment SAS x A x 0.001 = 0.0232 mg Typical body weight of human = 60 kg Systemic exposure dose (SED) SAS x A x 0.001/… = 0.00039 mg/kg bw No observed adverse effect level NOAEL = 3 mg/kg bw/d (90-day, oral, rat) Bioavailability 30%* = 0.9 mg/kg bw/d Margin of Safety adjusted NOAEL/SED = 2300 * based on the toxicokinetic study (ref. 21). 3.3.14 Discussion Physicochemical properties Tetrabromophenol Blue is used in oxidative- as well as in non-oxidative hair dye formulations at a maximum concentration of 0.2% on the scalp. The test material is not composed of a single substance. Although the main component is octabromo derivative of phenolsulfonphthalein, the material also contains heptabromo- and hexabromo- homologues. Analysis of different batches shows a large variation in composition o","endpoint":"dermal absorption","ingredient":"is misleading. The","loael_value":"","noael_unit":"mg/kg bw/d","noael_value":"= 0.9","page":34,"route":"oral","species":"rat","study_id":"sccs_o_197_noael_017"}
Regulatory source dermal absorption =3 mg/kg bw/d rat oral 90-day dermal absorption SOURCE_SUBDIR=sccs_o_197; REPORT_TITLE=OPINION ON Tetrabromophenol Blue, 4,4’-(4,5,6,7-tetrabromo-1,1- dioxido-3H-2,1-benzoxathiol-3-yliden)bis-2,6- dibromophenol (C183); OPINION_NUMBER=SCCS/1573/16; COMMITTEE=Scientific Committee on Consumer Safety (SCCS); REPORT_DATE=16 March 2016; VALUE_TEXT== 3; DOSE=-3-yliden)bis- 2,6-dibromophenol (C183) ___________________________________________________________________________________________ 34 CALCULATION OF THE MARGIN OF SAFETY (non-oxidative conditions) (In formulation, on head concentration 0.2%) Absorption through the skin A = 0.07 µg/cm² Skin Area surface SAS = 580 cm2 Dermal absorption per treatm...; EFFECT=-3-yliden)bis- 2,6-dibromophenol (C183) ___________________________________________________________________________________________ 34 CALCULATION OF THE MARGIN OF SAFETY (non-oxidative conditions) (In formulation, on head concentration 0.2%) Absorption through the skin A = 0.07 µg/cm² Skin Area surface SAS = 580 cm2 Dermal absorption per treatment SAS x A x 0.001 = 0.0406 mg Typical body weight of human = 60 kg Systemic exposure dose (SED) SAS x A x 0.001/… = 0.00068 mg/kg bw No observed adverse effect level NOAEL = 3 mg/kg bw/d (90-day, oral, rat) Bioavailability 30%* = 0.9 mg/kg bw/d Margin of Safety adjusted NOAEL/SED = 1300 * based on the toxicokinetic study (ref. 21). CALCULATION OF THE MARGIN OF SAFETY (oxidative conditions) (In formulation, on head concentration 0.2%) Absorption through the skin A = 0.04 µg/cm² Skin Area surface SAS = 580 cm2 Dermal absorption per treatment SAS x A x 0.001 = 0.0232 mg Typical body weight of human = 60 kg Systemic exposure dose (SED) SAS x A x 0.001/… = 0.00039 mg/kg bw No obse; CITATION=(ref. 21); CITATION_NUMBERS=[21]; REFERENCE=(ref. 21); DETAILS_JSON={"cas_number":"4430-25-5","citation":"(ref. 21)","dose":"-3-yliden)bis- 2,6-dibromophenol (C183) ___________________________________________________________________________________________ 34 CALCULATION OF THE MARGIN OF SAFETY (non-oxidative conditions) (In formulation, on head concentration 0.2%) Absorption through the skin A = 0.07 µg/cm² Skin Area surface SAS = 580 cm2 Dermal absorption per treatm...","duration":"90-day","effect":"-3-yliden)bis- 2,6-dibromophenol (C183) ___________________________________________________________________________________________ 34 CALCULATION OF THE MARGIN OF SAFETY (non-oxidative conditions) (In formulation, on head concentration 0.2%) Absorption through the skin A = 0.07 µg/cm² Skin Area surface SAS = 580 cm2 Dermal absorption per treatment SAS x A x 0.001 = 0.0406 mg Typical body weight of human = 60 kg Systemic exposure dose (SED) SAS x A x 0.001/… = 0.00068 mg/kg bw No observed adverse effect level NOAEL = 3 mg/kg bw/d (90-day, oral, rat) Bioavailability 30%* = 0.9 mg/kg bw/d Margin of Safety adjusted NOAEL/SED = 1300 * based on the toxicokinetic study (ref. 21). CALCULATION OF THE MARGIN OF SAFETY (oxidative conditions) (In formulation, on head concentration 0.2%) Absorption through the skin A = 0.04 µg/cm² Skin Area surface SAS = 580 cm2 Dermal absorption per treatment SAS x A x 0.001 = 0.0232 mg Typical body weight of human = 60 kg Systemic exposure dose (SED) SAS x A x 0.001/… = 0.00039 mg/kg bw No obse","endpoint":"dermal absorption","ingredient":"is misleading. The","loael_value":"","noael_unit":"mg/kg bw/d","noael_value":"= 3","page":34,"route":"oral","species":"rat","study_id":"sccs_o_197_noael_013"}
Regulatory source dermal absorption =3 mg/kg bw/d rat oral 90-day dermal absorption SOURCE_SUBDIR=sccs_o_197; REPORT_TITLE=OPINION ON Tetrabromophenol Blue, 4,4’-(4,5,6,7-tetrabromo-1,1- dioxido-3H-2,1-benzoxathiol-3-yliden)bis-2,6- dibromophenol (C183); OPINION_NUMBER=SCCS/1573/16; COMMITTEE=Scientific Committee on Consumer Safety (SCCS); REPORT_DATE=16 March 2016; VALUE_TEXT== 3; DOSE=ral, rat) Bioavailability 30%* = 0.9 mg/kg bw/d Margin of Safety adjusted NOAEL/SED = 1300 * based on the toxicokinetic study (ref.; EFFECT=ral, rat) Bioavailability 30%* = 0.9 mg/kg bw/d Margin of Safety adjusted NOAEL/SED = 1300 * based on the toxicokinetic study (ref. 21). CALCULATION OF THE MARGIN OF SAFETY (oxidative conditions) (In formulation, on head concentration 0.2%) Absorption through the skin A = 0.04 µg/cm² Skin Area surface SAS = 580 cm2 Dermal absorption per treatment SAS x A x 0.001 = 0.0232 mg Typical body weight of human = 60 kg Systemic exposure dose (SED) SAS x A x 0.001/… = 0.00039 mg/kg bw No observed adverse effect level NOAEL = 3 mg/kg bw/d (90-day, oral, rat) Bioavailability 30%* = 0.9 mg/kg bw/d Margin of Safety adjusted NOAEL/SED = 2300 * based on the toxicokinetic study (ref. 21). 3.3.14 Discussion Physicochemical properties Tetrabromophenol Blue is used in oxidative- as well as in non-oxidative hair dye formulations at a maximum concentration of 0.2% on the scalp. The test material is not composed of a single substance. Although the main component is octabromo derivative of phenolsulfonphthalein, the material also contains he; CITATION=(ref. 21); CITATION_NUMBERS=[21]; REFERENCE=(ref. 21); DETAILS_JSON={"cas_number":"4430-25-5","citation":"(ref. 21)","dose":"ral, rat) Bioavailability 30%* = 0.9 mg/kg bw/d Margin of Safety adjusted NOAEL/SED = 1300 * based on the toxicokinetic study (ref.","duration":"90-day","effect":"ral, rat) Bioavailability 30%* = 0.9 mg/kg bw/d Margin of Safety adjusted NOAEL/SED = 1300 * based on the toxicokinetic study (ref. 21). CALCULATION OF THE MARGIN OF SAFETY (oxidative conditions) (In formulation, on head concentration 0.2%) Absorption through the skin A = 0.04 µg/cm² Skin Area surface SAS = 580 cm2 Dermal absorption per treatment SAS x A x 0.001 = 0.0232 mg Typical body weight of human = 60 kg Systemic exposure dose (SED) SAS x A x 0.001/… = 0.00039 mg/kg bw No observed adverse effect level NOAEL = 3 mg/kg bw/d (90-day, oral, rat) Bioavailability 30%* = 0.9 mg/kg bw/d Margin of Safety adjusted NOAEL/SED = 2300 * based on the toxicokinetic study (ref. 21). 3.3.14 Discussion Physicochemical properties Tetrabromophenol Blue is used in oxidative- as well as in non-oxidative hair dye formulations at a maximum concentration of 0.2% on the scalp. The test material is not composed of a single substance. Although the main component is octabromo derivative of phenolsulfonphthalein, the material also contains he","endpoint":"dermal absorption","ingredient":"is misleading. The","loael_value":"","noael_unit":"mg/kg bw/d","noael_value":"= 3","page":34,"route":"oral","species":"rat","study_id":"sccs_o_197_noael_016"}
Regulatory source developmental toxicity 100 mg/kg bw/day - oral 90-day developmental toxicity SOURCE_SUBDIR=sccs_o_232; REPORT_TITLE=Final Opinion Version S Scientific Committee on Consumer Safety SCCS OPINION ON Tetrabromophenol Blue, 4,4’-(4,5,6,7-tetrabromo-1,1- dioxido-3H-2,1-benzoxathiol-3-yliden)bis-2,6-; OPINION_NUMBER=SCCS/1610/19; COMMITTEE=Scientific Committee on Consumer Safety (SCCS); REPORT_DATE=final version of 13 December 2019; VALUE_TEXT=100; DOSE=If a direct cholinergic effect was involved, a clear dose response relationship would be expected, i.e., a ten-fold difference in dose between the mid and high dose would be expected to lead to a dramatic increase in chromodacryorrhea, This was not observed.; EFFECT=ce of chromodacryorrhea in a treatment-related manner (discomfort after gavage, bad taste, etc.). If a direct cholinergic effect was involved, a clear dose response relationship would be expected, i.e., a ten-fold difference in dose between the mid and high dose would be expected to lead to a dramatic increase in chromodacryorrhea, This was not observed. Therefore, the applicant considers that a direct cholinergic effect of the test material is unlikely. Based on the arguments above, the applicant concludes that a NOAEL of 100 mg/kg bw/day (expressed as administered dose) is justified for the 90-day oral toxicity study. The applicant acknowledges that this difference in interpretation regarding the NOAEL from this study does not impact the MoS calculation because the applicant has used the NOAEL from the developmental toxicity study (3 mg/kg bw/day) for the calculation. Reassessment by the SCCS The current SCCS agrees with the previous evaluation of the SCCNFP in 2004, as well as with the reassessment of the previous SCCS, i.e.; CITATION_NUMBERS=[]; DETAILS_JSON={"cas_number":"4430-25-5","citation":"","dose":"If a direct cholinergic effect was involved, a clear dose response relationship would be expected, i.e., a ten-fold difference in dose between the mid and high dose would be expected to lead to a dramatic increase in chromodacryorrhea, This was not observed.","duration":"90-day","effect":"ce of chromodacryorrhea in a treatment-related manner (discomfort after gavage, bad taste, etc.). If a direct cholinergic effect was involved, a clear dose response relationship would be expected, i.e., a ten-fold difference in dose between the mid and high dose would be expected to lead to a dramatic increase in chromodacryorrhea, This was not observed. Therefore, the applicant considers that a direct cholinergic effect of the test material is unlikely. Based on the arguments above, the applicant concludes that a NOAEL of 100 mg/kg bw/day (expressed as administered dose) is justified for the 90-day oral toxicity study. The applicant acknowledges that this difference in interpretation regarding the NOAEL from this study does not impact the MoS calculation because the applicant has used the NOAEL from the developmental toxicity study (3 mg/kg bw/day) for the calculation. Reassessment by the SCCS The current SCCS agrees with the previous evaluation of the SCCNFP in 2004, as well as with the reassessment of the previous SCCS, i.e.","endpoint":"developmental toxicity","ingredient":"Tetrabromophenol Blue","loael_value":"","noael_unit":"mg/kg bw/day","noael_value":"100","page":32,"route":"oral","species":"","study_id":"sccs_o_232_noael_004"}
Regulatory source developmental toxicity 3 mg/kg bw/day - oral 90-day developmental toxicity SOURCE_SUBDIR=sccs_o_232; REPORT_TITLE=Final Opinion Version S Scientific Committee on Consumer Safety SCCS OPINION ON Tetrabromophenol Blue, 4,4’-(4,5,6,7-tetrabromo-1,1- dioxido-3H-2,1-benzoxathiol-3-yliden)bis-2,6-; OPINION_NUMBER=SCCS/1610/19; COMMITTEE=Scientific Committee on Consumer Safety (SCCS); REPORT_DATE=final version of 13 December 2019; VALUE_TEXT=3; DOSE=xpected, i.e., a ten-fold difference in dose between the mid and high dose would be expected to lead to a dramatic increase in chromodacryorrhea, This was not observed.; EFFECT=xpected, i.e., a ten-fold difference in dose between the mid and high dose would be expected to lead to a dramatic increase in chromodacryorrhea, This was not observed. Therefore, the applicant considers that a direct cholinergic effect of the test material is unlikely. Based on the arguments above, the applicant concludes that a NOAEL of 100 mg/kg bw/day (expressed as administered dose) is justified for the 90-day oral toxicity study. The applicant acknowledges that this difference in interpretation regarding the NOAEL from this study does not impact the MoS calculation because the applicant has used the NOAEL from the developmental toxicity study (3 mg/kg bw/day) for the calculation. Reassessment by the SCCS The current SCCS agrees with the previous evaluation of the SCCNFP in 2004, as well as with the reassessment of the previous SCCS, i.e. the NOAEL is 3 mg/kg bw/day based on the ophthalmological and haematological findings at the higher dose levels in this study. The NOAEL of 3 mg/kg bw/day is taken forward to the MoS calcu; CITATION_NUMBERS=[]; DETAILS_JSON={"cas_number":"4430-25-5","citation":"","dose":"xpected, i.e., a ten-fold difference in dose between the mid and high dose would be expected to lead to a dramatic increase in chromodacryorrhea, This was not observed.","duration":"90-day","effect":"xpected, i.e., a ten-fold difference in dose between the mid and high dose would be expected to lead to a dramatic increase in chromodacryorrhea, This was not observed. Therefore, the applicant considers that a direct cholinergic effect of the test material is unlikely. Based on the arguments above, the applicant concludes that a NOAEL of 100 mg/kg bw/day (expressed as administered dose) is justified for the 90-day oral toxicity study. The applicant acknowledges that this difference in interpretation regarding the NOAEL from this study does not impact the MoS calculation because the applicant has used the NOAEL from the developmental toxicity study (3 mg/kg bw/day) for the calculation. Reassessment by the SCCS The current SCCS agrees with the previous evaluation of the SCCNFP in 2004, as well as with the reassessment of the previous SCCS, i.e. the NOAEL is 3 mg/kg bw/day based on the ophthalmological and haematological findings at the higher dose levels in this study. The NOAEL of 3 mg/kg bw/day is taken forward to the MoS calcu","endpoint":"developmental toxicity","ingredient":"Tetrabromophenol Blue","loael_value":"","noael_unit":"mg/kg bw/day","noael_value":"3","page":32,"route":"oral","species":"","study_id":"sccs_o_232_noael_005"}
Regulatory source developmental toxicity 3 mg/kg bw/day - oral 90-day developmental toxicity SOURCE_SUBDIR=sccs_o_232; REPORT_TITLE=Final Opinion Version S Scientific Committee on Consumer Safety SCCS OPINION ON Tetrabromophenol Blue, 4,4’-(4,5,6,7-tetrabromo-1,1- dioxido-3H-2,1-benzoxathiol-3-yliden)bis-2,6-; OPINION_NUMBER=SCCS/1610/19; COMMITTEE=Scientific Committee on Consumer Safety (SCCS); REPORT_DATE=final version of 13 December 2019; VALUE_TEXT=3; DOSE=Based on the arguments above, the applicant concludes that a NOAEL of 100 mg/kg bw/day (expressed as administered dose) is justified for the 90-day oral toxicity study.; EFFECT=to lead to a dramatic increase in chromodacryorrhea, This was not observed. Therefore, the applicant considers that a direct cholinergic effect of the test material is unlikely. Based on the arguments above, the applicant concludes that a NOAEL of 100 mg/kg bw/day (expressed as administered dose) is justified for the 90-day oral toxicity study. The applicant acknowledges that this difference in interpretation regarding the NOAEL from this study does not impact the MoS calculation because the applicant has used the NOAEL from the developmental toxicity study (3 mg/kg bw/day) for the calculation. Reassessment by the SCCS The current SCCS agrees with the previous evaluation of the SCCNFP in 2004, as well as with the reassessment of the previous SCCS, i.e. the NOAEL is 3 mg/kg bw/day based on the ophthalmological and haematological findings at the higher dose levels in this study. The NOAEL of 3 mg/kg bw/day is taken forward to the MoS calculation.; CITATION_NUMBERS=[]; DETAILS_JSON={"cas_number":"4430-25-5","citation":"","dose":"Based on the arguments above, the applicant concludes that a NOAEL of 100 mg/kg bw/day (expressed as administered dose) is justified for the 90-day oral toxicity study.","duration":"90-day","effect":"to lead to a dramatic increase in chromodacryorrhea, This was not observed. Therefore, the applicant considers that a direct cholinergic effect of the test material is unlikely. Based on the arguments above, the applicant concludes that a NOAEL of 100 mg/kg bw/day (expressed as administered dose) is justified for the 90-day oral toxicity study. The applicant acknowledges that this difference in interpretation regarding the NOAEL from this study does not impact the MoS calculation because the applicant has used the NOAEL from the developmental toxicity study (3 mg/kg bw/day) for the calculation. Reassessment by the SCCS The current SCCS agrees with the previous evaluation of the SCCNFP in 2004, as well as with the reassessment of the previous SCCS, i.e. the NOAEL is 3 mg/kg bw/day based on the ophthalmological and haematological findings at the higher dose levels in this study. The NOAEL of 3 mg/kg bw/day is taken forward to the MoS calculation.","endpoint":"developmental toxicity","ingredient":"Tetrabromophenol Blue","loael_value":"","noael_unit":"mg/kg bw/day","noael_value":"3","page":32,"route":"oral","species":"","study_id":"sccs_o_232_noael_006"}
Regulatory source developmental toxicity 3 mg/kg bw/day - oral 90-day developmental toxicity SOURCE_SUBDIR=sccs_o_232; REPORT_TITLE=Final Opinion Version S Scientific Committee on Consumer Safety SCCS OPINION ON Tetrabromophenol Blue, 4,4’-(4,5,6,7-tetrabromo-1,1- dioxido-3H-2,1-benzoxathiol-3-yliden)bis-2,6-; OPINION_NUMBER=SCCS/1610/19; COMMITTEE=Scientific Committee on Consumer Safety (SCCS); REPORT_DATE=final version of 13 December 2019; VALUE_TEXT=3; DOSE=100 mg/kg bw/day (expressed as administered dose) is justified for the 90-day oral toxicity study.; EFFECT=100 mg/kg bw/day (expressed as administered dose) is justified for the 90-day oral toxicity study. The applicant acknowledges that this difference in interpretation regarding the NOAEL from this study does not impact the MoS calculation because the applicant has used the NOAEL from the developmental toxicity study (3 mg/kg bw/day) for the calculation. Reassessment by the SCCS The current SCCS agrees with the previous evaluation of the SCCNFP in 2004, as well as with the reassessment of the previous SCCS, i.e. the NOAEL is 3 mg/kg bw/day based on the ophthalmological and haematological findings at the higher dose levels in this study. The NOAEL of 3 mg/kg bw/day is taken forward to the MoS calculation.; CITATION_NUMBERS=[]; DETAILS_JSON={"cas_number":"4430-25-5","citation":"","dose":"100 mg/kg bw/day (expressed as administered dose) is justified for the 90-day oral toxicity study.","duration":"90-day","effect":"100 mg/kg bw/day (expressed as administered dose) is justified for the 90-day oral toxicity study. The applicant acknowledges that this difference in interpretation regarding the NOAEL from this study does not impact the MoS calculation because the applicant has used the NOAEL from the developmental toxicity study (3 mg/kg bw/day) for the calculation. Reassessment by the SCCS The current SCCS agrees with the previous evaluation of the SCCNFP in 2004, as well as with the reassessment of the previous SCCS, i.e. the NOAEL is 3 mg/kg bw/day based on the ophthalmological and haematological findings at the higher dose levels in this study. The NOAEL of 3 mg/kg bw/day is taken forward to the MoS calculation.","endpoint":"developmental toxicity","ingredient":"Tetrabromophenol Blue","loael_value":"","noael_unit":"mg/kg bw/day","noael_value":"3","page":32,"route":"oral","species":"","study_id":"sccs_o_232_noael_007"}
Regulatory source developmental toxicity 3 mg/kg bw/day - - developmental developmental toxicity SOURCE_SUBDIR=sccs_o_232; REPORT_TITLE=Final Opinion Version S Scientific Committee on Consumer Safety SCCS OPINION ON Tetrabromophenol Blue, 4,4’-(4,5,6,7-tetrabromo-1,1- dioxido-3H-2,1-benzoxathiol-3-yliden)bis-2,6-; OPINION_NUMBER=SCCS/1610/19; COMMITTEE=Scientific Committee on Consumer Safety (SCCS); REPORT_DATE=final version of 13 December 2019; VALUE_TEXT=3; DOSE=hat this difference in interpretation regarding the NOAEL from this study does not impact the MoS calculation because the applicant has used the NOAEL from the developmental toxicity study (3 mg/kg bw/day) for the calculation.; EFFECT=hat this difference in interpretation regarding the NOAEL from this study does not impact the MoS calculation because the applicant has used the NOAEL from the developmental toxicity study (3 mg/kg bw/day) for the calculation. Reassessment by the SCCS The current SCCS agrees with the previous evaluation of the SCCNFP in 2004, as well as with the reassessment of the previous SCCS, i.e. the NOAEL is 3 mg/kg bw/day based on the ophthalmological and haematological findings at the higher dose levels in this study. The NOAEL of 3 mg/kg bw/day is taken forward to the MoS calculation.; CITATION_NUMBERS=[]; DETAILS_JSON={"cas_number":"4430-25-5","citation":"","dose":"hat this difference in interpretation regarding the NOAEL from this study does not impact the MoS calculation because the applicant has used the NOAEL from the developmental toxicity study (3 mg/kg bw/day) for the calculation.","duration":"developmental","effect":"hat this difference in interpretation regarding the NOAEL from this study does not impact the MoS calculation because the applicant has used the NOAEL from the developmental toxicity study (3 mg/kg bw/day) for the calculation. Reassessment by the SCCS The current SCCS agrees with the previous evaluation of the SCCNFP in 2004, as well as with the reassessment of the previous SCCS, i.e. the NOAEL is 3 mg/kg bw/day based on the ophthalmological and haematological findings at the higher dose levels in this study. The NOAEL of 3 mg/kg bw/day is taken forward to the MoS calculation.","endpoint":"developmental toxicity","ingredient":"Tetrabromophenol Blue","loael_value":"","noael_unit":"mg/kg bw/day","noael_value":"3","page":32,"route":"","species":"","study_id":"sccs_o_232_noael_008"}
Regulatory source developmental toxicity 3 mg/kg bw/day - oral 90-day developmental toxicity SOURCE_SUBDIR=sccs_o_197; REPORT_TITLE=OPINION ON Tetrabromophenol Blue, 4,4’-(4,5,6,7-tetrabromo-1,1- dioxido-3H-2,1-benzoxathiol-3-yliden)bis-2,6- dibromophenol (C183); OPINION_NUMBER=SCCS/1573/16; COMMITTEE=Scientific Committee on Consumer Safety (SCCS); REPORT_DATE=16 March 2016; VALUE_TEXT=3; DOSE=xpected, i.e., a ten-fold difference in dose between the mid and high dose would be expected to lead to a dramatic increase in chromodacryorrhea, This was not observed.; EFFECT=xpected, i.e., a ten-fold difference in dose between the mid and high dose would be expected to lead to a dramatic increase in chromodacryorrhea, This was not observed. Therefore, the applicant considers that a direct cholinergic effect of the test material is unlikely. Based on the arguments above, the applicant concludes that a NOAEL of 100 mg/kg bw/day (expressed as administered dose) is justified for the 90-day oral toxicity study. The applicant acknowledges that this difference in interpretation regarding the NOAEL from this study does not impact the MoS calculation because the applicant has used the NOAEL from the developmental toxicity study (3 mg/kg bw/day) for the calculation. Reassessment by the SCCS in 2016 The current SCCS agrees with the previous evaluation of the SCCNFP in 2004, as well as with the reassessment of the previous SCCS, i.e. the NOAEL is 3 mg/kg bw/day based on the ophthalmological and haematological findings at the higher dose levels in this study. The NOAEL of 3 mg/kg bw/day is taken forward to the; CITATION_NUMBERS=[]; DETAILS_JSON={"cas_number":"4430-25-5","citation":"","dose":"xpected, i.e., a ten-fold difference in dose between the mid and high dose would be expected to lead to a dramatic increase in chromodacryorrhea, This was not observed.","duration":"90-day","effect":"xpected, i.e., a ten-fold difference in dose between the mid and high dose would be expected to lead to a dramatic increase in chromodacryorrhea, This was not observed. Therefore, the applicant considers that a direct cholinergic effect of the test material is unlikely. Based on the arguments above, the applicant concludes that a NOAEL of 100 mg/kg bw/day (expressed as administered dose) is justified for the 90-day oral toxicity study. The applicant acknowledges that this difference in interpretation regarding the NOAEL from this study does not impact the MoS calculation because the applicant has used the NOAEL from the developmental toxicity study (3 mg/kg bw/day) for the calculation. Reassessment by the SCCS in 2016 The current SCCS agrees with the previous evaluation of the SCCNFP in 2004, as well as with the reassessment of the previous SCCS, i.e. the NOAEL is 3 mg/kg bw/day based on the ophthalmological and haematological findings at the higher dose levels in this study. The NOAEL of 3 mg/kg bw/day is taken forward to the","endpoint":"developmental toxicity","ingredient":"is misleading. The","loael_value":"","noael_unit":"mg/kg bw/day","noael_value":"3","page":24,"route":"oral","species":"","study_id":"sccs_o_197_noael_004"}
Regulatory source developmental toxicity 3 mg/kg bw/day - oral 90-day developmental toxicity SOURCE_SUBDIR=sccs_o_197; REPORT_TITLE=OPINION ON Tetrabromophenol Blue, 4,4’-(4,5,6,7-tetrabromo-1,1- dioxido-3H-2,1-benzoxathiol-3-yliden)bis-2,6- dibromophenol (C183); OPINION_NUMBER=SCCS/1573/16; COMMITTEE=Scientific Committee on Consumer Safety (SCCS); REPORT_DATE=16 March 2016; VALUE_TEXT=3; DOSE=Based on the arguments above, the applicant concludes that a NOAEL of 100 mg/kg bw/day (expressed as administered dose) is justified for the 90-day oral toxicity study.; EFFECT=to lead to a dramatic increase in chromodacryorrhea, This was not observed. Therefore, the applicant considers that a direct cholinergic effect of the test material is unlikely. Based on the arguments above, the applicant concludes that a NOAEL of 100 mg/kg bw/day (expressed as administered dose) is justified for the 90-day oral toxicity study. The applicant acknowledges that this difference in interpretation regarding the NOAEL from this study does not impact the MoS calculation because the applicant has used the NOAEL from the developmental toxicity study (3 mg/kg bw/day) for the calculation. Reassessment by the SCCS in 2016 The current SCCS agrees with the previous evaluation of the SCCNFP in 2004, as well as with the reassessment of the previous SCCS, i.e. the NOAEL is 3 mg/kg bw/day based on the ophthalmological and haematological findings at the higher dose levels in this study. The NOAEL of 3 mg/kg bw/day is taken forward to the MoS calculation. 3.3.5.3 Chronic (> 12 months) toxicity 3.3.6 Mutagenicity / Genotoxicity; CITATION_NUMBERS=[]; DETAILS_JSON={"cas_number":"4430-25-5","citation":"","dose":"Based on the arguments above, the applicant concludes that a NOAEL of 100 mg/kg bw/day (expressed as administered dose) is justified for the 90-day oral toxicity study.","duration":"90-day","effect":"to lead to a dramatic increase in chromodacryorrhea, This was not observed. Therefore, the applicant considers that a direct cholinergic effect of the test material is unlikely. Based on the arguments above, the applicant concludes that a NOAEL of 100 mg/kg bw/day (expressed as administered dose) is justified for the 90-day oral toxicity study. The applicant acknowledges that this difference in interpretation regarding the NOAEL from this study does not impact the MoS calculation because the applicant has used the NOAEL from the developmental toxicity study (3 mg/kg bw/day) for the calculation. Reassessment by the SCCS in 2016 The current SCCS agrees with the previous evaluation of the SCCNFP in 2004, as well as with the reassessment of the previous SCCS, i.e. the NOAEL is 3 mg/kg bw/day based on the ophthalmological and haematological findings at the higher dose levels in this study. The NOAEL of 3 mg/kg bw/day is taken forward to the MoS calculation. 3.3.5.3 Chronic (> 12 months) toxicity 3.3.6 Mutagenicity / Genotoxicity","endpoint":"developmental toxicity","ingredient":"is misleading. The","loael_value":"","noael_unit":"mg/kg bw/day","noael_value":"3","page":24,"route":"oral","species":"","study_id":"sccs_o_197_noael_005"}
Regulatory source developmental toxicity 3 mg/kg bw/day - oral 90-day developmental toxicity SOURCE_SUBDIR=sccs_o_197; REPORT_TITLE=OPINION ON Tetrabromophenol Blue, 4,4’-(4,5,6,7-tetrabromo-1,1- dioxido-3H-2,1-benzoxathiol-3-yliden)bis-2,6- dibromophenol (C183); OPINION_NUMBER=SCCS/1573/16; COMMITTEE=Scientific Committee on Consumer Safety (SCCS); REPORT_DATE=16 March 2016; VALUE_TEXT=3; DOSE=bw/day (expressed as administered dose) is justified for the 90-day oral toxicity study.; EFFECT=bw/day (expressed as administered dose) is justified for the 90-day oral toxicity study. The applicant acknowledges that this difference in interpretation regarding the NOAEL from this study does not impact the MoS calculation because the applicant has used the NOAEL from the developmental toxicity study (3 mg/kg bw/day) for the calculation. Reassessment by the SCCS in 2016 The current SCCS agrees with the previous evaluation of the SCCNFP in 2004, as well as with the reassessment of the previous SCCS, i.e. the NOAEL is 3 mg/kg bw/day based on the ophthalmological and haematological findings at the higher dose levels in this study. The NOAEL of 3 mg/kg bw/day is taken forward to the MoS calculation. 3.3.5.3 Chronic (> 12 months) toxicity 3.3.6 Mutagenicity / Genotoxicity 3.3.6.1 Mutagenicity / Genotoxicity in vitro Taken from SCCNFP/0797/04, SCCS/1426/11 Bacterial Reverse Mutation Assay Guideline: OECD 471 (July 1997) Species/strain: S. typhimurium TA 98; TA 100; TA102; TA1537; TA1535; CITATION_NUMBERS=[]; DETAILS_JSON={"cas_number":"4430-25-5","citation":"","dose":"bw/day (expressed as administered dose) is justified for the 90-day oral toxicity study.","duration":"90-day","effect":"bw/day (expressed as administered dose) is justified for the 90-day oral toxicity study. The applicant acknowledges that this difference in interpretation regarding the NOAEL from this study does not impact the MoS calculation because the applicant has used the NOAEL from the developmental toxicity study (3 mg/kg bw/day) for the calculation. Reassessment by the SCCS in 2016 The current SCCS agrees with the previous evaluation of the SCCNFP in 2004, as well as with the reassessment of the previous SCCS, i.e. the NOAEL is 3 mg/kg bw/day based on the ophthalmological and haematological findings at the higher dose levels in this study. The NOAEL of 3 mg/kg bw/day is taken forward to the MoS calculation. 3.3.5.3 Chronic (> 12 months) toxicity 3.3.6 Mutagenicity / Genotoxicity 3.3.6.1 Mutagenicity / Genotoxicity in vitro Taken from SCCNFP/0797/04, SCCS/1426/11 Bacterial Reverse Mutation Assay Guideline: OECD 471 (July 1997) Species/strain: S. typhimurium TA 98; TA 100; TA102; TA1537; TA1535","endpoint":"developmental toxicity","ingredient":"is misleading. The","loael_value":"","noael_unit":"mg/kg bw/day","noael_value":"3","page":24,"route":"oral","species":"","study_id":"sccs_o_197_noael_006"}
Regulatory source developmental toxicity 3 mg/kg bw/day - - developmental developmental toxicity SOURCE_SUBDIR=sccs_o_197; REPORT_TITLE=OPINION ON Tetrabromophenol Blue, 4,4’-(4,5,6,7-tetrabromo-1,1- dioxido-3H-2,1-benzoxathiol-3-yliden)bis-2,6- dibromophenol (C183); OPINION_NUMBER=SCCS/1573/16; COMMITTEE=Scientific Committee on Consumer Safety (SCCS); REPORT_DATE=16 March 2016; VALUE_TEXT=3; DOSE=difference in interpretation regarding the NOAEL from this study does not impact the MoS calculation because the applicant has used the NOAEL from the developmental toxicity study (3 mg/kg bw/day) for the calculation.; EFFECT=difference in interpretation regarding the NOAEL from this study does not impact the MoS calculation because the applicant has used the NOAEL from the developmental toxicity study (3 mg/kg bw/day) for the calculation. Reassessment by the SCCS in 2016 The current SCCS agrees with the previous evaluation of the SCCNFP in 2004, as well as with the reassessment of the previous SCCS, i.e. the NOAEL is 3 mg/kg bw/day based on the ophthalmological and haematological findings at the higher dose levels in this study. The NOAEL of 3 mg/kg bw/day is taken forward to the MoS calculation. 3.3.5.3 Chronic (> 12 months) toxicity 3.3.6 Mutagenicity / Genotoxicity 3.3.6.1 Mutagenicity / Genotoxicity in vitro Taken from SCCNFP/0797/04, SCCS/1426/11 Bacterial Reverse Mutation Assay Guideline: OECD 471 (July 1997) Species/strain: S. typhimurium TA 98; TA 100; TA102; TA1537; TA1535; CITATION_NUMBERS=[]; DETAILS_JSON={"cas_number":"4430-25-5","citation":"","dose":"difference in interpretation regarding the NOAEL from this study does not impact the MoS calculation because the applicant has used the NOAEL from the developmental toxicity study (3 mg/kg bw/day) for the calculation.","duration":"developmental","effect":"difference in interpretation regarding the NOAEL from this study does not impact the MoS calculation because the applicant has used the NOAEL from the developmental toxicity study (3 mg/kg bw/day) for the calculation. Reassessment by the SCCS in 2016 The current SCCS agrees with the previous evaluation of the SCCNFP in 2004, as well as with the reassessment of the previous SCCS, i.e. the NOAEL is 3 mg/kg bw/day based on the ophthalmological and haematological findings at the higher dose levels in this study. The NOAEL of 3 mg/kg bw/day is taken forward to the MoS calculation. 3.3.5.3 Chronic (> 12 months) toxicity 3.3.6 Mutagenicity / Genotoxicity 3.3.6.1 Mutagenicity / Genotoxicity in vitro Taken from SCCNFP/0797/04, SCCS/1426/11 Bacterial Reverse Mutation Assay Guideline: OECD 471 (July 1997) Species/strain: S. typhimurium TA 98; TA 100; TA102; TA1537; TA1535","endpoint":"developmental toxicity","ingredient":"is misleading. The","loael_value":"","noael_unit":"mg/kg bw/day","noael_value":"3","page":24,"route":"","species":"","study_id":"sccs_o_197_noael_007"}
Regulatory source developmental toxicity 100 mg/kg bw/day - oral 90-day developmental toxicity SOURCE_SUBDIR=sccs_o_197; REPORT_TITLE=OPINION ON Tetrabromophenol Blue, 4,4’-(4,5,6,7-tetrabromo-1,1- dioxido-3H-2,1-benzoxathiol-3-yliden)bis-2,6- dibromophenol (C183); OPINION_NUMBER=SCCS/1573/16; COMMITTEE=Scientific Committee on Consumer Safety (SCCS); REPORT_DATE=16 March 2016; VALUE_TEXT=100; DOSE=If a direct cholinergic effect was involved, a clear dose response relationship would be expected, i.e., a ten-fold difference in dose between the mid and high dose would be expected to lead to a dramatic increase in chromodacryorrhea, This was not observed.; EFFECT=ce of chromodacryorrhea in a treatment-related manner (discomfort after gavage, bad taste, etc.). If a direct cholinergic effect was involved, a clear dose response relationship would be expected, i.e., a ten-fold difference in dose between the mid and high dose would be expected to lead to a dramatic increase in chromodacryorrhea, This was not observed. Therefore, the applicant considers that a direct cholinergic effect of the test material is unlikely. Based on the arguments above, the applicant concludes that a NOAEL of 100 mg/kg bw/day (expressed as administered dose) is justified for the 90-day oral toxicity study. The applicant acknowledges that this difference in interpretation regarding the NOAEL from this study does not impact the MoS calculation because the applicant has used the NOAEL from the developmental toxicity study (3 mg/kg bw/day) for the calculation. Reassessment by the SCCS in 2016 The current SCCS agrees with the previous evaluation of the SCCNFP in 2004, as well as with the reassessment of the previous SC; CITATION_NUMBERS=[]; DETAILS_JSON={"cas_number":"4430-25-5","citation":"","dose":"If a direct cholinergic effect was involved, a clear dose response relationship would be expected, i.e., a ten-fold difference in dose between the mid and high dose would be expected to lead to a dramatic increase in chromodacryorrhea, This was not observed.","duration":"90-day","effect":"ce of chromodacryorrhea in a treatment-related manner (discomfort after gavage, bad taste, etc.). If a direct cholinergic effect was involved, a clear dose response relationship would be expected, i.e., a ten-fold difference in dose between the mid and high dose would be expected to lead to a dramatic increase in chromodacryorrhea, This was not observed. Therefore, the applicant considers that a direct cholinergic effect of the test material is unlikely. Based on the arguments above, the applicant concludes that a NOAEL of 100 mg/kg bw/day (expressed as administered dose) is justified for the 90-day oral toxicity study. The applicant acknowledges that this difference in interpretation regarding the NOAEL from this study does not impact the MoS calculation because the applicant has used the NOAEL from the developmental toxicity study (3 mg/kg bw/day) for the calculation. Reassessment by the SCCS in 2016 The current SCCS agrees with the previous evaluation of the SCCNFP in 2004, as well as with the reassessment of the previous SC","endpoint":"developmental toxicity","ingredient":"is misleading. The","loael_value":"","noael_unit":"mg/kg bw/day","noael_value":"100","page":24,"route":"oral","species":"","study_id":"sccs_o_197_noael_003"}
Regulatory source genotoxicity 4 - human - - genotoxicity SOURCE_SUBDIR=sccs_o_232; REPORT_TITLE=Final Opinion Version S Scientific Committee on Consumer Safety SCCS OPINION ON Tetrabromophenol Blue, 4,4’-(4,5,6,7-tetrabromo-1,1- dioxido-3H-2,1-benzoxathiol-3-yliden)bis-2,6-; OPINION_NUMBER=SCCS/1610/19; COMMITTEE=Scientific Committee on Consumer Safety (SCCS); REPORT_DATE=final version of 13 December 2019; VALUE_TEXT=unclear:crease of the major components, homologue (4) and (5) in batch 7215600060 by maximally 2.49 fold versus batch TBFB2/02/30 is covered. This is supported by (a) the absence of in vitro genotoxicity in the Ames Test and the In Vitro Human Lymphocyte Micronucleus Assay (b) the absence of skin and mucous membrane irritation or skin sensitization properties of batch TBFB2/02/30 at concentrations 10 fold above use condition (c) a MoS of 529 and 923 for non-oxidative and oxidative conditions, respectively, when the lowest NOAEL for batch TBFB2/02/30 was adjusted for the increases in the two major components of batch 7215600060; EFFECT=crease of the major components, homologue (4) and (5) in batch 7215600060 by maximally 2.49 fold versus batch TBFB2/02/30 is covered. This is supported by (a) the absence of in vitro genotoxicity in the Ames Test and the In Vitro Human Lymphocyte Micronucleus Assay (b) the absence of skin and mucous membrane irritation or skin sensitization properties of batch TBFB2/02/30 at concentrations 10 fold above use condition (c) a MoS of 529 and 923 for non-oxidative and oxidative conditions, respectively, when the lowest NOAEL for batch TBFB2/02/30 was adjusted for the increases in the two major components of batch 7215600060; CITATION_NUMBERS=[]; DETAILS_JSON={"cas_number":"4430-25-5","citation":"","dose":"","duration":"","effect":"crease of the major components, homologue (4) and (5) in batch 7215600060 by maximally 2.49 fold versus batch TBFB2/02/30 is covered. This is supported by (a) the absence of in vitro genotoxicity in the Ames Test and the In Vitro Human Lymphocyte Micronucleus Assay (b) the absence of skin and mucous membrane irritation or skin sensitization properties of batch TBFB2/02/30 at concentrations 10 fold above use condition (c) a MoS of 529 and 923 for non-oxidative and oxidative conditions, respectively, when the lowest NOAEL for batch TBFB2/02/30 was adjusted for the increases in the two major components of batch 7215600060","endpoint":"genotoxicity","ingredient":"Tetrabromophenol Blue","loael_value":"","noael_unit":"","noael_value":"unclear:crease of the major components, homologue (4) and (5) in batch 7215600060 by maximally 2.49 fold versus batch TBFB2/02/30 is covered. This is supported by (a) the absence of in vitro genotoxicity in the Ames Test and the In Vitro Human Lymphocyte Micronucleus Assay (b) the absence of skin and mucous membrane irritation or skin sensitization properties of batch TBFB2/02/30 at concentrations 10 fold above use condition (c) a MoS of 529 and 923 for non-oxidative and oxidative conditions, respectively, when the lowest NOAEL for batch TBFB2/02/30 was adjusted for the increases in the two major components of batch 7215600060","page":12,"route":"","species":"human","study_id":"sccs_o_232_noael_001"}
Regulatory source repeated dose toxicity 3 mg/kg bw/day rat oral Sub-chronic repeated dose toxicity SOURCE_SUBDIR=sccs_o_101; REPORT_TITLE=OPINION ON Tetrabromophenol Blue COLIPA n° C183; OPINION_NUMBER=SCCS/1426/11; COMMITTEE=Scientific Committee on Consumer Safety (SCCS); REPORT_DATE=18 September 2012; VALUE_TEXT=3; DOSE=High dose animals showed an increase in white blood cell counts (males) and increases in cholesterol and glucose (females) while at 10 mg/kg bw/day only one male showed a high glucose value.; EFFECT=treatment-related effects. High dose animals showed an increase in white blood cell counts (males) and increases in cholesterol and glucose (females) while at 10 mg/kg bw/day only one male showed a high glucose value. Discolouration of the caecum related to the staining properties of the test substance was noted in high dose animals. Missing values in male control organ and body weights make it difficult to evaluate possible substance-related changes in absolute and relative body weights. The authors established a NOAEL of 3 mg/kg bw/day. Ref.: 2b, subm I 3.3.5.2. Sub-chronic (90 days) toxicity (oral, dermal) Taken from SCCNFP/0797/04, re-evaluated Guideline: OECD 408 (1998) Species/strain: SPF-bred Wistar rats Group size: 10 males and 10 females per dose group Test substance: Tetrabromophenol Blue dissolved in water containing 5.3% polyglycol 600 and 4.2% of a 50% aqueous decyl glucoside solution Batch: TBFB3/02/30 Purity: 96.7-98.8% Dose levels: 0, 3, 10 and 100 mg/kg bw/day by oral gavage Route: oral gavage GLP: in complian; CITATION=Ref.: 2b, subm I 3; CITATION_NUMBERS=[2,3]; REFERENCE=Ref.: 2b, subm I 3; DETAILS_JSON={"cas_number":"4430-25-5","citation":"Ref.: 2b, subm I 3","dose":"High dose animals showed an increase in white blood cell counts (males) and increases in cholesterol and glucose (females) while at 10 mg/kg bw/day only one male showed a high glucose value.","duration":"Sub-chronic","effect":"treatment-related effects. High dose animals showed an increase in white blood cell counts (males) and increases in cholesterol and glucose (females) while at 10 mg/kg bw/day only one male showed a high glucose value. Discolouration of the caecum related to the staining properties of the test substance was noted in high dose animals. Missing values in male control organ and body weights make it difficult to evaluate possible substance-related changes in absolute and relative body weights. The authors established a NOAEL of 3 mg/kg bw/day. Ref.: 2b, subm I 3.3.5.2. Sub-chronic (90 days) toxicity (oral, dermal) Taken from SCCNFP/0797/04, re-evaluated Guideline: OECD 408 (1998) Species/strain: SPF-bred Wistar rats Group size: 10 males and 10 females per dose group Test substance: Tetrabromophenol Blue dissolved in water containing 5.3% polyglycol 600 and 4.2% of a 50% aqueous decyl glucoside solution Batch: TBFB3/02/30 Purity: 96.7-98.8% Dose levels: 0, 3, 10 and 100 mg/kg bw/day by oral gavage Route: oral gavage GLP: in complian","endpoint":"repeated dose toxicity","ingredient":"Tetrabromophenol Blue","loael_value":"","noael_unit":"mg/kg bw/day","noael_value":"3","page":16,"route":"oral","species":"rat","study_id":"sccs_o_101_noael_001"}
Regulatory source repeated dose toxicity =0.0434 mg/kg bw/d rat oral sub-chronic repeated dose toxicity SOURCE_SUBDIR=sccs_o_101; REPORT_TITLE=OPINION ON Tetrabromophenol Blue COLIPA n° C183; OPINION_NUMBER=SCCS/1426/11; COMMITTEE=Scientific Committee on Consumer Safety (SCCS); REPORT_DATE=18 September 2012; VALUE_TEXT== 0.0434; DOSE=Safety evaluation (including calculation of the MoS) CALCULATION OF THE MARGIN OF SAFETY INCI Name Non oxidative conditions Absorption through the skin A = 4.49 µg/cm2 Skin Area surface SAS = 580 cm2 Dermal absorption per treatment SAS x A x 0.001 = 2.60 mg Typical body weight of human = 60 kg Systemic exposure dose SAS x A x 0.001/60 = 0.0434 m...; EFFECT=SCCS/1426/11 Opinion on Tetrabromophenol Blue ___________________________________________________________________________________________ 26 3.3.13. Safety evaluation (including calculation of the MoS) CALCULATION OF THE MARGIN OF SAFETY INCI Name Non oxidative conditions Absorption through the skin A = 4.49 µg/cm2 Skin Area surface SAS = 580 cm2 Dermal absorption per treatment SAS x A x 0.001 = 2.60 mg Typical body weight of human = 60 kg Systemic exposure dose SAS x A x 0.001/60 = 0.0434 mg/kg bw/d No Observed Adverse Effect Level NOAEL = 3 mg/kg bw/d (rat, oral, teratogenicity and sub-chronic toxicity) Corrected for 30% oral bio-availability (Ref. 21) = 0.9 mg/kg bw/d MOS = 21 3.3.14. Discussion Physico-chemical properties Tetrabromophenol Blue is used in oxidative- as well as in non-oxidative hair dye formulations at a maximum concentration of 0.2% on the scalp. The name Tetrabromophenol Blue of the test material is misleading, since the main component is an octabromo-derivative (42%, quantitative HPLC analysis using standard referen; CITATION=(Ref. 21); CITATION_NUMBERS=[21]; REFERENCE=(Ref. 21); DETAILS_JSON={"cas_number":"4430-25-5","citation":"(Ref. 21)","dose":"Safety evaluation (including calculation of the MoS) CALCULATION OF THE MARGIN OF SAFETY INCI Name Non oxidative conditions Absorption through the skin A = 4.49 µg/cm2 Skin Area surface SAS = 580 cm2 Dermal absorption per treatment SAS x A x 0.001 = 2.60 mg Typical body weight of human = 60 kg Systemic exposure dose SAS x A x 0.001/60 = 0.0434 m...","duration":"sub-chronic","effect":"SCCS/1426/11 Opinion on Tetrabromophenol Blue ___________________________________________________________________________________________ 26 3.3.13. Safety evaluation (including calculation of the MoS) CALCULATION OF THE MARGIN OF SAFETY INCI Name Non oxidative conditions Absorption through the skin A = 4.49 µg/cm2 Skin Area surface SAS = 580 cm2 Dermal absorption per treatment SAS x A x 0.001 = 2.60 mg Typical body weight of human = 60 kg Systemic exposure dose SAS x A x 0.001/60 = 0.0434 mg/kg bw/d No Observed Adverse Effect Level NOAEL = 3 mg/kg bw/d (rat, oral, teratogenicity and sub-chronic toxicity) Corrected for 30% oral bio-availability (Ref. 21) = 0.9 mg/kg bw/d MOS = 21 3.3.14. Discussion Physico-chemical properties Tetrabromophenol Blue is used in oxidative- as well as in non-oxidative hair dye formulations at a maximum concentration of 0.2% on the scalp. The name Tetrabromophenol Blue of the test material is misleading, since the main component is an octabromo-derivative (42%, quantitative HPLC analysis using standard referen","endpoint":"repeated dose toxicity","ingredient":"Tetrabromophenol Blue","loael_value":"","noael_unit":"mg/kg bw/d","noael_value":"= 0.0434","page":26,"route":"oral","species":"rat","study_id":"sccs_o_101_noael_009"}
Regulatory source repeated dose toxicity =3 mg/kg bw/d rat oral sub-chronic repeated dose toxicity SOURCE_SUBDIR=sccs_o_101; REPORT_TITLE=OPINION ON Tetrabromophenol Blue COLIPA n° C183; OPINION_NUMBER=SCCS/1426/11; COMMITTEE=Scientific Committee on Consumer Safety (SCCS); REPORT_DATE=18 September 2012; VALUE_TEXT== 3; DOSE=Safety evaluation (including calculation of the MoS) CALCULATION OF THE MARGIN OF SAFETY INCI Name Non oxidative conditions Absorption through the skin A = 4.49 µg/cm2 Skin Area surface SAS = 580 cm2 Dermal absorption per treatment SAS x A x 0.001 = 2.60 mg Typical body weight of human = 60 kg Systemic exposure dose SAS x A x 0.001/60 = 0.0434 m...; EFFECT=trabromophenol Blue ___________________________________________________________________________________________ 26 3.3.13. Safety evaluation (including calculation of the MoS) CALCULATION OF THE MARGIN OF SAFETY INCI Name Non oxidative conditions Absorption through the skin A = 4.49 µg/cm2 Skin Area surface SAS = 580 cm2 Dermal absorption per treatment SAS x A x 0.001 = 2.60 mg Typical body weight of human = 60 kg Systemic exposure dose SAS x A x 0.001/60 = 0.0434 mg/kg bw/d No Observed Adverse Effect Level NOAEL = 3 mg/kg bw/d (rat, oral, teratogenicity and sub-chronic toxicity) Corrected for 30% oral bio-availability (Ref. 21) = 0.9 mg/kg bw/d MOS = 21 3.3.14. Discussion Physico-chemical properties Tetrabromophenol Blue is used in oxidative- as well as in non-oxidative hair dye formulations at a maximum concentration of 0.2% on the scalp. The name Tetrabromophenol Blue of the test material is misleading, since the main component is an octabromo-derivative (42%, quantitative HPLC analysis using standard reference mat; CITATION=(Ref. 21); CITATION_NUMBERS=[21]; REFERENCE=(Ref. 21); DETAILS_JSON={"cas_number":"4430-25-5","citation":"(Ref. 21)","dose":"Safety evaluation (including calculation of the MoS) CALCULATION OF THE MARGIN OF SAFETY INCI Name Non oxidative conditions Absorption through the skin A = 4.49 µg/cm2 Skin Area surface SAS = 580 cm2 Dermal absorption per treatment SAS x A x 0.001 = 2.60 mg Typical body weight of human = 60 kg Systemic exposure dose SAS x A x 0.001/60 = 0.0434 m...","duration":"sub-chronic","effect":"trabromophenol Blue ___________________________________________________________________________________________ 26 3.3.13. Safety evaluation (including calculation of the MoS) CALCULATION OF THE MARGIN OF SAFETY INCI Name Non oxidative conditions Absorption through the skin A = 4.49 µg/cm2 Skin Area surface SAS = 580 cm2 Dermal absorption per treatment SAS x A x 0.001 = 2.60 mg Typical body weight of human = 60 kg Systemic exposure dose SAS x A x 0.001/60 = 0.0434 mg/kg bw/d No Observed Adverse Effect Level NOAEL = 3 mg/kg bw/d (rat, oral, teratogenicity and sub-chronic toxicity) Corrected for 30% oral bio-availability (Ref. 21) = 0.9 mg/kg bw/d MOS = 21 3.3.14. Discussion Physico-chemical properties Tetrabromophenol Blue is used in oxidative- as well as in non-oxidative hair dye formulations at a maximum concentration of 0.2% on the scalp. The name Tetrabromophenol Blue of the test material is misleading, since the main component is an octabromo-derivative (42%, quantitative HPLC analysis using standard reference mat","endpoint":"repeated dose toxicity","ingredient":"Tetrabromophenol Blue","loael_value":"","noael_unit":"mg/kg bw/d","noael_value":"= 3","page":26,"route":"oral","species":"rat","study_id":"sccs_o_101_noael_010"}
Regulatory source repeated dose toxicity 10 mg/kg bw/day - oral 90 day repeated dose toxicity SOURCE_SUBDIR=sccs_o_101; REPORT_TITLE=OPINION ON Tetrabromophenol Blue COLIPA n° C183; OPINION_NUMBER=SCCS/1426/11; COMMITTEE=Scientific Committee on Consumer Safety (SCCS); REPORT_DATE=18 September 2012; VALUE_TEXT=10; DOSE=General toxicity No data on acute toxicity were submitted The study authors established a NOAEL of 10 mg/kg bw/day for the subchronic study.; EFFECT=fter oral administration whereas dermal absorption was low (1.2%). The systemically available portion was readily distributed into all organs and excreted mainly via the faeces, as the parent compound and to a lesser extent, its metabolites. In the dermal part of the study, chromodacryorrhoea from the nose and eye were observed. Similar systemic effects on the eyes were seen in the 90 day study at the high and medium doses. General toxicity No data on acute toxicity were submitted The study authors established a NOAEL of 10 mg/kg bw/day for the subchronic study. However, the SCCNFP set the NOAEL as 3 mg/kg bw/day based on the ophthalmological (corneal opacity), clinical signs and haematological findings. The SCCS concurs with this decision. The ophthalmic effects were considered to be systemic cholinergic effects due to an underlying stressor effect rather than direct eye contact. A NOAEL for embryo-foetal effects was derived at 3 mg/kg bw/day. No data on reproductive toxicity were provided. Mutagenicity Tetrabromophenol Blue; CITATION_NUMBERS=[]; DETAILS_JSON={"cas_number":"4430-25-5","citation":"","dose":"General toxicity No data on acute toxicity were submitted The study authors established a NOAEL of 10 mg/kg bw/day for the subchronic study.","duration":"90 day","effect":"fter oral administration whereas dermal absorption was low (1.2%). The systemically available portion was readily distributed into all organs and excreted mainly via the faeces, as the parent compound and to a lesser extent, its metabolites. In the dermal part of the study, chromodacryorrhoea from the nose and eye were observed. Similar systemic effects on the eyes were seen in the 90 day study at the high and medium doses. General toxicity No data on acute toxicity were submitted The study authors established a NOAEL of 10 mg/kg bw/day for the subchronic study. However, the SCCNFP set the NOAEL as 3 mg/kg bw/day based on the ophthalmological (corneal opacity), clinical signs and haematological findings. The SCCS concurs with this decision. The ophthalmic effects were considered to be systemic cholinergic effects due to an underlying stressor effect rather than direct eye contact. A NOAEL for embryo-foetal effects was derived at 3 mg/kg bw/day. No data on reproductive toxicity were provided. Mutagenicity Tetrabromophenol Blue","endpoint":"repeated dose toxicity","ingredient":"Tetrabromophenol Blue","loael_value":"","noael_unit":"mg/kg bw/day","noael_value":"10","page":27,"route":"oral","species":"","study_id":"sccs_o_101_noael_011"}
Regulatory source repeated dose toxicity 3 mg/kg bw/day - dermal 90 day repeated dose toxicity SOURCE_SUBDIR=sccs_o_101; REPORT_TITLE=OPINION ON Tetrabromophenol Blue COLIPA n° C183; OPINION_NUMBER=SCCS/1426/11; COMMITTEE=Scientific Committee on Consumer Safety (SCCS); REPORT_DATE=18 September 2012; VALUE_TEXT=3; DOSE=General toxicity No data on acute toxicity were submitted The study authors established a NOAEL of 10 mg/kg bw/day for the subchronic study.; EFFECT=ally available portion was readily distributed into all organs and excreted mainly via the faeces, as the parent compound and to a lesser extent, its metabolites. In the dermal part of the study, chromodacryorrhoea from the nose and eye were observed. Similar systemic effects on the eyes were seen in the 90 day study at the high and medium doses. General toxicity No data on acute toxicity were submitted The study authors established a NOAEL of 10 mg/kg bw/day for the subchronic study. However, the SCCNFP set the NOAEL as 3 mg/kg bw/day based on the ophthalmological (corneal opacity), clinical signs and haematological findings. The SCCS concurs with this decision. The ophthalmic effects were considered to be systemic cholinergic effects due to an underlying stressor effect rather than direct eye contact. A NOAEL for embryo-foetal effects was derived at 3 mg/kg bw/day. No data on reproductive toxicity were provided. Mutagenicity Tetrabromophenol Blue has been tested for the three genetic endpoints: gene mutations, structural an; CITATION_NUMBERS=[]; DETAILS_JSON={"cas_number":"4430-25-5","citation":"","dose":"General toxicity No data on acute toxicity were submitted The study authors established a NOAEL of 10 mg/kg bw/day for the subchronic study.","duration":"90 day","effect":"ally available portion was readily distributed into all organs and excreted mainly via the faeces, as the parent compound and to a lesser extent, its metabolites. In the dermal part of the study, chromodacryorrhoea from the nose and eye were observed. Similar systemic effects on the eyes were seen in the 90 day study at the high and medium doses. General toxicity No data on acute toxicity were submitted The study authors established a NOAEL of 10 mg/kg bw/day for the subchronic study. However, the SCCNFP set the NOAEL as 3 mg/kg bw/day based on the ophthalmological (corneal opacity), clinical signs and haematological findings. The SCCS concurs with this decision. The ophthalmic effects were considered to be systemic cholinergic effects due to an underlying stressor effect rather than direct eye contact. A NOAEL for embryo-foetal effects was derived at 3 mg/kg bw/day. No data on reproductive toxicity were provided. Mutagenicity Tetrabromophenol Blue has been tested for the three genetic endpoints: gene mutations, structural an","endpoint":"repeated dose toxicity","ingredient":"Tetrabromophenol Blue","loael_value":"","noael_unit":"mg/kg bw/day","noael_value":"3","page":27,"route":"dermal","species":"","study_id":"sccs_o_101_noael_012"}
Regulatory source repeated dose toxicity 3 mg/kg bw/day - - 90 day repeated dose toxicity SOURCE_SUBDIR=sccs_o_101; REPORT_TITLE=OPINION ON Tetrabromophenol Blue COLIPA n° C183; OPINION_NUMBER=SCCS/1426/11; COMMITTEE=Scientific Committee on Consumer Safety (SCCS); REPORT_DATE=18 September 2012; VALUE_TEXT=3; DOSE=General toxicity No data on acute toxicity were submitted The study authors established a NOAEL of 10 mg/kg bw/day for the subchronic study.; EFFECT=in the 90 day study at the high and medium doses. General toxicity No data on acute toxicity were submitted The study authors established a NOAEL of 10 mg/kg bw/day for the subchronic study. However, the SCCNFP set the NOAEL as 3 mg/kg bw/day based on the ophthalmological (corneal opacity), clinical signs and haematological findings. The SCCS concurs with this decision. The ophthalmic effects were considered to be systemic cholinergic effects due to an underlying stressor effect rather than direct eye contact. A NOAEL for embryo-foetal effects was derived at 3 mg/kg bw/day. No data on reproductive toxicity were provided. Mutagenicity Tetrabromophenol Blue has been tested for the three genetic endpoints: gene mutations, structural and numerical chromosomal aberrations. The test agent did not induce gene mutations in bacteria and mammalian cells. In an in vitro micronucleus assay the substance did not induce an increase in the number of cells with micronuclei and was also negative in an in vivo micronucleus assay. It can theref; CITATION_NUMBERS=[]; DETAILS_JSON={"cas_number":"4430-25-5","citation":"","dose":"General toxicity No data on acute toxicity were submitted The study authors established a NOAEL of 10 mg/kg bw/day for the subchronic study.","duration":"90 day","effect":"in the 90 day study at the high and medium doses. General toxicity No data on acute toxicity were submitted The study authors established a NOAEL of 10 mg/kg bw/day for the subchronic study. However, the SCCNFP set the NOAEL as 3 mg/kg bw/day based on the ophthalmological (corneal opacity), clinical signs and haematological findings. The SCCS concurs with this decision. The ophthalmic effects were considered to be systemic cholinergic effects due to an underlying stressor effect rather than direct eye contact. A NOAEL for embryo-foetal effects was derived at 3 mg/kg bw/day. No data on reproductive toxicity were provided. Mutagenicity Tetrabromophenol Blue has been tested for the three genetic endpoints: gene mutations, structural and numerical chromosomal aberrations. The test agent did not induce gene mutations in bacteria and mammalian cells. In an in vitro micronucleus assay the substance did not induce an increase in the number of cells with micronuclei and was also negative in an in vivo micronucleus assay. It can theref","endpoint":"repeated dose toxicity","ingredient":"Tetrabromophenol Blue","loael_value":"","noael_unit":"mg/kg bw/day","noael_value":"3","page":27,"route":"","species":"","study_id":"sccs_o_101_noael_013"}
Regulatory source repeated dose toxicity 100 mg/kg bw/day - - subchronic repeated dose toxicity SOURCE_SUBDIR=sccs_o_232; REPORT_TITLE=Final Opinion Version S Scientific Committee on Consumer Safety SCCS OPINION ON Tetrabromophenol Blue, 4,4’-(4,5,6,7-tetrabromo-1,1- dioxido-3H-2,1-benzoxathiol-3-yliden)bis-2,6-; OPINION_NUMBER=SCCS/1610/19; COMMITTEE=Scientific Committee on Consumer Safety (SCCS); REPORT_DATE=final version of 13 December 2019; VALUE_TEXT=100; DOSE=The study authors established a NOAEL of 100 mg/kg bw/day for the subchronic study.; EFFECT=important to avoid any future ambiguity over the composition of C183 intended for use in hair dye formulations. The SCCS assessment is therefore limited to C183 that has a chemical composition profile comparable to the 'market quality' batch (7215600060), as noted in Table 2 in this Opinion - i.e. it contains at least 83% octabromo homologue, no more than 16% heptabromo homologue, and around 0.2% any other bromo homologue. General toxicity No data on acute toxicity were submitted. The study authors established a NOAEL of 100 mg/kg bw/day for the subchronic study. However, the SCCNFP set the NOAEL as 3 mg/kg bw/day based on the ophthalmological (corneal opacity), clinical signs and haematological findings. The SCCS concurs with this decision. The ophthalmic effects were considered to be systemic cholinergic effects due to an underlying stressor effect rather than direct eye contact. A NOAEL for embryo-foetal effects was derived at 3 mg/kg bw/day. No data on reproductive toxicity were provided. Irritation/sensitisation Tetrabrom; CITATION_NUMBERS=[]; DETAILS_JSON={"cas_number":"4430-25-5","citation":"","dose":"The study authors established a NOAEL of 100 mg/kg bw/day for the subchronic study.","duration":"subchronic","effect":"important to avoid any future ambiguity over the composition of C183 intended for use in hair dye formulations. The SCCS assessment is therefore limited to C183 that has a chemical composition profile comparable to the 'market quality' batch (7215600060), as noted in Table 2 in this Opinion - i.e. it contains at least 83% octabromo homologue, no more than 16% heptabromo homologue, and around 0.2% any other bromo homologue. General toxicity No data on acute toxicity were submitted. The study authors established a NOAEL of 100 mg/kg bw/day for the subchronic study. However, the SCCNFP set the NOAEL as 3 mg/kg bw/day based on the ophthalmological (corneal opacity), clinical signs and haematological findings. The SCCS concurs with this decision. The ophthalmic effects were considered to be systemic cholinergic effects due to an underlying stressor effect rather than direct eye contact. A NOAEL for embryo-foetal effects was derived at 3 mg/kg bw/day. No data on reproductive toxicity were provided. Irritation/sensitisation Tetrabrom","endpoint":"repeated dose toxicity","ingredient":"Tetrabromophenol Blue","loael_value":"","noael_unit":"mg/kg bw/day","noael_value":"100","page":47,"route":"","species":"","study_id":"sccs_o_232_noael_020"}
Regulatory source repeated dose toxicity 3 mg/kg bw/day - - subchronic repeated dose toxicity SOURCE_SUBDIR=sccs_o_232; REPORT_TITLE=Final Opinion Version S Scientific Committee on Consumer Safety SCCS OPINION ON Tetrabromophenol Blue, 4,4’-(4,5,6,7-tetrabromo-1,1- dioxido-3H-2,1-benzoxathiol-3-yliden)bis-2,6-; OPINION_NUMBER=SCCS/1610/19; COMMITTEE=Scientific Committee on Consumer Safety (SCCS); REPORT_DATE=final version of 13 December 2019; VALUE_TEXT=3; DOSE=The study authors established a NOAEL of 100 mg/kg bw/day for the subchronic study.; EFFECT=or use in hair dye formulations. The SCCS assessment is therefore limited to C183 that has a chemical composition profile comparable to the 'market quality' batch (7215600060), as noted in Table 2 in this Opinion - i.e. it contains at least 83% octabromo homologue, no more than 16% heptabromo homologue, and around 0.2% any other bromo homologue. General toxicity No data on acute toxicity were submitted. The study authors established a NOAEL of 100 mg/kg bw/day for the subchronic study. However, the SCCNFP set the NOAEL as 3 mg/kg bw/day based on the ophthalmological (corneal opacity), clinical signs and haematological findings. The SCCS concurs with this decision. The ophthalmic effects were considered to be systemic cholinergic effects due to an underlying stressor effect rather than direct eye contact. A NOAEL for embryo-foetal effects was derived at 3 mg/kg bw/day. No data on reproductive toxicity were provided. Irritation/sensitisation Tetrabromophenol Blue is not a skin irritant. Based on the degree and persistence of the; CITATION_NUMBERS=[]; DETAILS_JSON={"cas_number":"4430-25-5","citation":"","dose":"The study authors established a NOAEL of 100 mg/kg bw/day for the subchronic study.","duration":"subchronic","effect":"or use in hair dye formulations. The SCCS assessment is therefore limited to C183 that has a chemical composition profile comparable to the 'market quality' batch (7215600060), as noted in Table 2 in this Opinion - i.e. it contains at least 83% octabromo homologue, no more than 16% heptabromo homologue, and around 0.2% any other bromo homologue. General toxicity No data on acute toxicity were submitted. The study authors established a NOAEL of 100 mg/kg bw/day for the subchronic study. However, the SCCNFP set the NOAEL as 3 mg/kg bw/day based on the ophthalmological (corneal opacity), clinical signs and haematological findings. The SCCS concurs with this decision. The ophthalmic effects were considered to be systemic cholinergic effects due to an underlying stressor effect rather than direct eye contact. A NOAEL for embryo-foetal effects was derived at 3 mg/kg bw/day. No data on reproductive toxicity were provided. Irritation/sensitisation Tetrabromophenol Blue is not a skin irritant. Based on the degree and persistence of the","endpoint":"repeated dose toxicity","ingredient":"Tetrabromophenol Blue","loael_value":"","noael_unit":"mg/kg bw/day","noael_value":"3","page":47,"route":"","species":"","study_id":"sccs_o_232_noael_021"}
Regulatory source repeated dose toxicity 3 mg/kg bw/day human dermal subchronic repeated dose toxicity SOURCE_SUBDIR=sccs_o_232; REPORT_TITLE=Final Opinion Version S Scientific Committee on Consumer Safety SCCS OPINION ON Tetrabromophenol Blue, 4,4’-(4,5,6,7-tetrabromo-1,1- dioxido-3H-2,1-benzoxathiol-3-yliden)bis-2,6-; OPINION_NUMBER=SCCS/1610/19; COMMITTEE=Scientific Committee on Consumer Safety (SCCS); REPORT_DATE=final version of 13 December 2019; VALUE_TEXT=3; DOSE=The study authors established a NOAEL of 100 mg/kg bw/day for the subchronic study.; EFFECT=ogue, and around 0.2% any other bromo homologue. General toxicity No data on acute toxicity were submitted. The study authors established a NOAEL of 100 mg/kg bw/day for the subchronic study. However, the SCCNFP set the NOAEL as 3 mg/kg bw/day based on the ophthalmological (corneal opacity), clinical signs and haematological findings. The SCCS concurs with this decision. The ophthalmic effects were considered to be systemic cholinergic effects due to an underlying stressor effect rather than direct eye contact. A NOAEL for embryo-foetal effects was derived at 3 mg/kg bw/day. No data on reproductive toxicity were provided. Irritation/sensitisation Tetrabromophenol Blue is not a skin irritant. Based on the degree and persistence of the corneal injury, the pure substance poses a risk of serious damage to eyes. Tetrabromophenol Blue in a dilution of 2% is not irritant for the eyes. Tetrabromophenol Blue does not pose a sensitising risk to consumers when used as intended. Dermal absorption Two new in vitro experiments using human s; CITATION_NUMBERS=[]; DETAILS_JSON={"cas_number":"4430-25-5","citation":"","dose":"The study authors established a NOAEL of 100 mg/kg bw/day for the subchronic study.","duration":"subchronic","effect":"ogue, and around 0.2% any other bromo homologue. General toxicity No data on acute toxicity were submitted. The study authors established a NOAEL of 100 mg/kg bw/day for the subchronic study. However, the SCCNFP set the NOAEL as 3 mg/kg bw/day based on the ophthalmological (corneal opacity), clinical signs and haematological findings. The SCCS concurs with this decision. The ophthalmic effects were considered to be systemic cholinergic effects due to an underlying stressor effect rather than direct eye contact. A NOAEL for embryo-foetal effects was derived at 3 mg/kg bw/day. No data on reproductive toxicity were provided. Irritation/sensitisation Tetrabromophenol Blue is not a skin irritant. Based on the degree and persistence of the corneal injury, the pure substance poses a risk of serious damage to eyes. Tetrabromophenol Blue in a dilution of 2% is not irritant for the eyes. Tetrabromophenol Blue does not pose a sensitising risk to consumers when used as intended. Dermal absorption Two new in vitro experiments using human s","endpoint":"repeated dose toxicity","ingredient":"Tetrabromophenol Blue","loael_value":"","noael_unit":"mg/kg bw/day","noael_value":"3","page":47,"route":"dermal","species":"human","study_id":"sccs_o_232_noael_022"}
Regulatory source repeated dose toxicity 3 mg/kg bw/day - - subchronic repeated dose toxicity SOURCE_SUBDIR=sccs_o_197; REPORT_TITLE=OPINION ON Tetrabromophenol Blue, 4,4’-(4,5,6,7-tetrabromo-1,1- dioxido-3H-2,1-benzoxathiol-3-yliden)bis-2,6- dibromophenol (C183); OPINION_NUMBER=SCCS/1573/16; COMMITTEE=Scientific Committee on Consumer Safety (SCCS); REPORT_DATE=16 March 2016; VALUE_TEXT=3; DOSE=The study authors established a NOAEL of 100 mg/kg bw/day for the subchronic study.; EFFECT=ed Tetrabromophenolphthalein. Using the same terminology, the correct name for the octabromo derivative should be Tetrabromo Bromophenol Blue (instead of Tetrabromophenol Blue). The analytical data provided by the Applicant suggests that the substance is sufficiently stable (>90%) during storage, and also under oxidative conditions during use. General toxicity No data on acute toxicity were submitted. The study authors established a NOAEL of 100 mg/kg bw/day for the subchronic study. However, the SCCNFP set the NOAEL as 3 mg/kg bw/day based on the ophthalmological (corneal opacity), clinical signs and haematological findings. The SCCS concurs with this decision. The ophthalmic effects were considered to be systemic cholinergic effects due to an underlying stressor effect rather than direct eye contact. A NOAEL for embryo-foetal effects was derived at 3 mg/kg bw/day. No data on reproductive toxicity were provided. Irritation/sensitisation Tetrabromophenol Blue is not a skin irritant. Based on the degree and persistence of the; CITATION_NUMBERS=[]; DETAILS_JSON={"cas_number":"4430-25-5","citation":"","dose":"The study authors established a NOAEL of 100 mg/kg bw/day for the subchronic study.","duration":"subchronic","effect":"ed Tetrabromophenolphthalein. Using the same terminology, the correct name for the octabromo derivative should be Tetrabromo Bromophenol Blue (instead of Tetrabromophenol Blue). The analytical data provided by the Applicant suggests that the substance is sufficiently stable (>90%) during storage, and also under oxidative conditions during use. General toxicity No data on acute toxicity were submitted. The study authors established a NOAEL of 100 mg/kg bw/day for the subchronic study. However, the SCCNFP set the NOAEL as 3 mg/kg bw/day based on the ophthalmological (corneal opacity), clinical signs and haematological findings. The SCCS concurs with this decision. The ophthalmic effects were considered to be systemic cholinergic effects due to an underlying stressor effect rather than direct eye contact. A NOAEL for embryo-foetal effects was derived at 3 mg/kg bw/day. No data on reproductive toxicity were provided. Irritation/sensitisation Tetrabromophenol Blue is not a skin irritant. Based on the degree and persistence of the","endpoint":"repeated dose toxicity","ingredient":"is misleading. The","loael_value":"","noael_unit":"mg/kg bw/day","noael_value":"3","page":35,"route":"","species":"","study_id":"sccs_o_197_noael_019"}
Regulatory source repeated dose toxicity 3 mg/kg bw/day human dermal subchronic repeated dose toxicity SOURCE_SUBDIR=sccs_o_197; REPORT_TITLE=OPINION ON Tetrabromophenol Blue, 4,4’-(4,5,6,7-tetrabromo-1,1- dioxido-3H-2,1-benzoxathiol-3-yliden)bis-2,6- dibromophenol (C183); OPINION_NUMBER=SCCS/1573/16; COMMITTEE=Scientific Committee on Consumer Safety (SCCS); REPORT_DATE=16 March 2016; VALUE_TEXT=3; DOSE=The study authors established a NOAEL of 100 mg/kg bw/day for the subchronic study.; EFFECT=and also under oxidative conditions during use. General toxicity No data on acute toxicity were submitted. The study authors established a NOAEL of 100 mg/kg bw/day for the subchronic study. However, the SCCNFP set the NOAEL as 3 mg/kg bw/day based on the ophthalmological (corneal opacity), clinical signs and haematological findings. The SCCS concurs with this decision. The ophthalmic effects were considered to be systemic cholinergic effects due to an underlying stressor effect rather than direct eye contact. A NOAEL for embryo-foetal effects was derived at 3 mg/kg bw/day. No data on reproductive toxicity were provided. Irritation/sensitisation Tetrabromophenol Blue is not a skin irritant. Based on the degree and persistence of the corneal injury, the pure substance poses a risk of serious damage to eyes. Tetrabromophenol Blue in a dilution of 2% is not irritant for the eyes. Tetrabromophenol Blue does not pose a sensitising risk to consumers when used as intended. Dermal absorption Two new in vitro experiments using human; CITATION_NUMBERS=[]; DETAILS_JSON={"cas_number":"4430-25-5","citation":"","dose":"The study authors established a NOAEL of 100 mg/kg bw/day for the subchronic study.","duration":"subchronic","effect":"and also under oxidative conditions during use. General toxicity No data on acute toxicity were submitted. The study authors established a NOAEL of 100 mg/kg bw/day for the subchronic study. However, the SCCNFP set the NOAEL as 3 mg/kg bw/day based on the ophthalmological (corneal opacity), clinical signs and haematological findings. The SCCS concurs with this decision. The ophthalmic effects were considered to be systemic cholinergic effects due to an underlying stressor effect rather than direct eye contact. A NOAEL for embryo-foetal effects was derived at 3 mg/kg bw/day. No data on reproductive toxicity were provided. Irritation/sensitisation Tetrabromophenol Blue is not a skin irritant. Based on the degree and persistence of the corneal injury, the pure substance poses a risk of serious damage to eyes. Tetrabromophenol Blue in a dilution of 2% is not irritant for the eyes. Tetrabromophenol Blue does not pose a sensitising risk to consumers when used as intended. Dermal absorption Two new in vitro experiments using human","endpoint":"repeated dose toxicity","ingredient":"is misleading. The","loael_value":"","noael_unit":"mg/kg bw/day","noael_value":"3","page":35,"route":"dermal","species":"human","study_id":"sccs_o_197_noael_020"}
Regulatory source repeated dose toxicity 100 mg/kg bw/day - - subchronic repeated dose toxicity SOURCE_SUBDIR=sccs_o_197; REPORT_TITLE=OPINION ON Tetrabromophenol Blue, 4,4’-(4,5,6,7-tetrabromo-1,1- dioxido-3H-2,1-benzoxathiol-3-yliden)bis-2,6- dibromophenol (C183); OPINION_NUMBER=SCCS/1573/16; COMMITTEE=Scientific Committee on Consumer Safety (SCCS); REPORT_DATE=16 March 2016; VALUE_TEXT=100; DOSE=The study authors established a NOAEL of 100 mg/kg bw/day for the subchronic study.; EFFECT=respective non- sulfonated derivative is also a well-known compound which is named Tetrabromophenolphthalein. Using the same terminology, the correct name for the octabromo derivative should be Tetrabromo Bromophenol Blue (instead of Tetrabromophenol Blue). The analytical data provided by the Applicant suggests that the substance is sufficiently stable (>90%) during storage, and also under oxidative conditions during use. General toxicity No data on acute toxicity were submitted. The study authors established a NOAEL of 100 mg/kg bw/day for the subchronic study. However, the SCCNFP set the NOAEL as 3 mg/kg bw/day based on the ophthalmological (corneal opacity), clinical signs and haematological findings. The SCCS concurs with this decision. The ophthalmic effects were considered to be systemic cholinergic effects due to an underlying stressor effect rather than direct eye contact. A NOAEL for embryo-foetal effects was derived at 3 mg/kg bw/day. No data on reproductive toxicity were provided. Irritation/sensitisation Tetrabro; CITATION_NUMBERS=[]; DETAILS_JSON={"cas_number":"4430-25-5","citation":"","dose":"The study authors established a NOAEL of 100 mg/kg bw/day for the subchronic study.","duration":"subchronic","effect":"respective non- sulfonated derivative is also a well-known compound which is named Tetrabromophenolphthalein. Using the same terminology, the correct name for the octabromo derivative should be Tetrabromo Bromophenol Blue (instead of Tetrabromophenol Blue). The analytical data provided by the Applicant suggests that the substance is sufficiently stable (>90%) during storage, and also under oxidative conditions during use. General toxicity No data on acute toxicity were submitted. The study authors established a NOAEL of 100 mg/kg bw/day for the subchronic study. However, the SCCNFP set the NOAEL as 3 mg/kg bw/day based on the ophthalmological (corneal opacity), clinical signs and haematological findings. The SCCS concurs with this decision. The ophthalmic effects were considered to be systemic cholinergic effects due to an underlying stressor effect rather than direct eye contact. A NOAEL for embryo-foetal effects was derived at 3 mg/kg bw/day. No data on reproductive toxicity were provided. Irritation/sensitisation Tetrabro","endpoint":"repeated dose toxicity","ingredient":"is misleading. The","loael_value":"","noael_unit":"mg/kg bw/day","noael_value":"100","page":35,"route":"","species":"","study_id":"sccs_o_197_noael_018"}
openFDA substances 4 endpoints
Source Endpoint Type Value Unit Species Route Duration Study Type Reference
openFDA substances FDA UNII substance identifier S6FO6931N7 UNII - - - chemical {"approval_status":null,"molecular_formula":"C19H6Br8O5S","source_table":"substance_identifiers_fda","substance_class":"chemical","unii_code":"S6FO6931N7"}
openFDA substances FDA UNII substance identifier S6FO6931N7 UNII - - - chemical {"approval_status":null,"molecular_formula":"C19H6Br8O5S","source_table":"substance_identifiers_fda","substance_class":"chemical","unii_code":"S6FO6931N7"}
openFDA substances FDA UNII substance identifier S6FO6931N7 UNII - - - chemical {"approval_status":null,"molecular_formula":"C19H6Br8O5S","source_table":"substance_identifiers_fda","substance_class":"chemical","unii_code":"S6FO6931N7"}
openFDA substances FDA UNII substance identifier S6FO6931N7 UNII - - - chemical {"approval_status":null,"molecular_formula":"C19H6Br8O5S","source_table":"substance_identifiers_fda","substance_class":"chemical","unii_code":"S6FO6931N7"}