NOAEL Studies
Cosmetic Ingredient
Dihydroxyindoline NOAEL Studies
INCI: DIHYDROXYINDOLINE
CAS: 29539-03-5
Raw No Observed Adverse Effect Level endpoint records grouped by source. This page does not render calculated Margin of Safety values.
COSMOS_DB 2 endpoints
| Source | Endpoint Type | Value | Unit | Species | Route | Duration | Study Type | Reference |
|---|---|---|---|---|---|---|---|---|
| COSMOS_DB | LOAEL | 20 | mg/kg bw/day | rat | oral | 13 week | Subchronic | SCCNFP; Pharmakon Europe, France. Study No 328/512; Henkel KGaA Report No 9501030 (1995) |
| COSMOS_DB | NOAEL | 10 | mg/kg bw/day | rat | oral | 13 week | Subchronic | SCCNFP; Pharmakon Europe, France. Study No 328/512; Henkel KGaA Report No 9501030 (1995) |
SCCNFP_vision_codex 28 endpoints
| Source | Endpoint Type | Value | Unit | Species | Route | Duration | Study Type | Reference |
|---|---|---|---|---|---|---|---|---|
| SCCNFP_vision_codex | NOAEL | =180 | mg/kg bw/day | rat | - | 4 weeks | NOAEL study | {"citation":"Ref. : 12 Guideline : OECD 408 Species/strain : Sprague-Dawley rat, Ico:OFA,SD (IOPs Caw) strain Group size : 5 males + 5 females 3 males+3 females (week 4, interim kill, test groups only","dose":"females and spleen weight was increased in both male and female high dose groups.","effect":"females and spleen weight was increased in both male and female high dose groups. After 4 weeks without treatment organ weights were comparable to controls. Histopathological changes were recorded in all treated animals but most notably at 180mg/kg bw/day. In particular discoloration within the kidney tubules and of the duodenum was reported in all treated groups with a dose-related increase in severity. These changes were also seen in treated animals at the end of the recovery period. The study did not identify a NOAEL. Ref. : 12 Guideline : OECD 408 Species/strain : Sprague-Dawley rat, Ico:OFA,SD (IOPs Caw) strain Group size : 5 males + 5 females 3 males+3 females (week 4, interim kill, test groups only) 5 males +5 females (week13-17 recovery groups, control + high dose) Test substance : SAT 930384 in aqueous solution Batch no : 4354/76 (purity 98.2%) Dose levels : 0, 5, 10 and 20 mg/kg bw/day in 5ml/kg pH2.5 Treatment period : 13 weeks + 4 week recovery GLP : in compliance Groups of 5 male and 5 female rats were dosed with the","page":7,"pdf":"out_193.pdf","row_type":"noael_study","study_id":"out_193_noael_001"} |
| SCCNFP_vision_codex | NOAEL | =20 | mg/kg bw/day | rat | - | - | NOAEL study | {"citation":"Ref. : 13","dose":"nt period there was a dose-related discoloration of urine at 10 and 20 mg/kg bw/day, which was more marked in the males.","effect":"nt period there was a dose-related discoloration of urine at 10 and 20 mg/kg bw/day, which was more marked in the males. After the recovery period, the urine colour of all treated animals was comparable to controls. Body weight gain and food consumption were comparable in all dose groups. There were no eye lesions. Microscopically, dose-related pigmentation was reported in the kidney tubules and duodenal villi of all treated rats, and was also present at the end of the recovery period. The study did not identify a NOAEL. No blood analyses were performed and therefore it is not possible to determine whether the observed pigmentation was associated with functional disturbances. Ref. : 13","page":7,"pdf":"out_193.pdf","row_type":"noael_study","study_id":"out_193_noael_002"} |
| SCCNFP_vision_codex | NOAEL | =10 | mg/kg/day | rat | dermal | Sub-chronic | repeated dose toxicity | {"citation":"Ref. : 19 2","dose":"ysiological background of brownish pigmentation, treatment-related exogenous pigments were found in kidneys of animals receiving doses of at least 20 mg/kg/day, with only occasional pigments found at the lowest dose (10 mg/kg/day).","effect":"ysiological background of brownish pigmentation, treatment-related exogenous pigments were found in kidneys of animals receiving doses of at least 20 mg/kg/day, with only occasional pigments found at the lowest dose (10 mg/kg/day). There were neither functional nor histological findings indicative for intestinal or renal injury, whether in treated or untreated animals. Due to the fact that if even minor signs of exogenous pigments were found in kidneys of rats dosed with 20 mg/kg/day, the no-observed effect-level (NOEL) was established at 10 mg/kg/day. Ref. : 19 2.3.8. Sub-chronic dermal toxicity No data 2.3.9. Sub-chronic inhalation toxicity No data","page":9,"pdf":"out_193.pdf","row_type":"noael_study","study_id":"out_193_noael_004"} |
| SCCNFP_vision_codex | NOAEL | =240 | mg/kg bw/day | rat | dermal | - | dermal absorption | {"citation":"Ref. : 15, 16 2","dose":"The mean numbers of corpora lutea, implantation sites, post-implantation loss, live foetuses and foetal body weights were similar for control and treated groups.","effect":"at it was not treatment-related. No abortions were observed. Food consumption and body weight gain were not affected by treatment. No macroscopic abnormalities were observed in any treatment group. The mean numbers of corpora lutea, implantation sites, post-implantation loss, live foetuses and foetal body weights were similar for control and treated groups. No treatment-related foetal malformations were observed. The only effect noted was generalised oedema in one foetus from a dam treated with 60mg/kg bw/day. The NOAEL for maternal toxicity and for embryo-foetal development was 240 mg/kg bw/day. Ref. : 15, 16 2.7. Toxicokinetics (incl. Percutaneous Absorption) 2.7.1 Percutaneous absorption in vivo Guideline : OECD 417 Species/strain : Sprague-Dawley rat, Him:OFA, SPF strain Group size : 6 females Route : Topical Test substance : 14C-labelled dihydroxyindoline (radiochemical purity >98%) Unlabelled material charge no: 1; SAT No. 920933 (purity not stated) Dose : 205 mg on 9 cm2 Exposure period : 30 minutes GLP : in compliance Lab","page":13,"pdf":"out_193.pdf","row_type":"noael_study","study_id":"out_193_noael_005"} |
| SCCNFP_vision_codex | NOAEL | =10 | mg/kg | rat | oral | 90 day | dermal absorption | {"dose":"Safety evaluation CALCULATION OF THE MARGIN OF SAFETY (Dihydroxyindoline HBr) (Air oxidative/semi-permanent) Based on a usage volume of 50 ml, containing at maximum 2 % Maximum absorption through the skin A (µg/cm2) = 1766 µg/cm2 Typical body weight of human = 60 kg Skin Area surface SAS (cm2) = 700 cm2 Dermal absorption per treatment SAS x A x...","effect":"_________________________________________________ 18/19 2.11. Safety evaluation CALCULATION OF THE MARGIN OF SAFETY (Dihydroxyindoline HBr) (Air oxidative/semi-permanent) Based on a usage volume of 50 ml, containing at maximum 2 % Maximum absorption through the skin A (µg/cm2) = 1766 µg/cm2 Typical body weight of human = 60 kg Skin Area surface SAS (cm2) = 700 cm2 Dermal absorption per treatment SAS x A x 0.001 = 1236 µg Systemic exposure dose (SED) SAS x A x 0.001/60 = 0.021 mg/kg No observed effect level (mg/kg) NOEL = 10 mg/kg (rat, 90 day, oral) Margin of Safety NOEL / SED = 476 2.12. Conclusions Insufficient information is provided on potential impurities. The database on toxicological properties is poor. Acute toxicity, irritation, sensitisation and embryotoxicity have been adequately investigated, following appropriate guidelines and GLP where relevant. It was irritant to the rabbit eye, but not skin when tested neat, and it is unlikely that similar results would occur under realistic conditions of use. It has shown sensi","page":18,"pdf":"out_193.pdf","row_type":"noael_study","study_id":"out_193_noael_006"} |
| SCCNFP_vision_codex | NOAEL | =10 | mg/kg bw/day | rat | oral | subchronic | repeated dose toxicity | {"dose":"Three subchronic oral dosing studies in rats indicate a NOEL of 10 mg/kg bw/day.","effect":"ies. The database on toxicological properties is poor. Acute toxicity, irritation, sensitisation and embryotoxicity have been adequately investigated, following appropriate guidelines and GLP where relevant. It was irritant to the rabbit eye, but not skin when tested neat, and it is unlikely that similar results would occur under realistic conditions of use. It has shown sensitising potential and formulations should be labelled with a warning in this respect. Three subchronic oral dosing studies in rats indicate a NOEL of 10 mg/kg bw/day. Skin penetration has been investigated in the rat in vivo. Sufficient information on tissue distribution and recovery is provided to assume that the results are acceptable. The percutaneous absorption study was performed with a 1.0 % formulation, where, in case of a semi-permanent hair dye, the foreseen use concentration is 2.0%. Comparing the NOEL with the maximum systemic exposure dose in humans indicates a safety margin of 476. A 147 was tested in bacterial cells for gene mutation in differe","page":18,"pdf":"out_193.pdf","row_type":"noael_study","study_id":"out_193_noael_008"} |
| SCCNFP_vision_codex | NOAEL | =2 | % | rat | oral | subchronic | repeated dose toxicity | {"dose":"Three subchronic oral dosing studies in rats indicate a NOEL of 10 mg/kg bw/day.","effect":"wn sensitising potential and formulations should be labelled with a warning in this respect. Three subchronic oral dosing studies in rats indicate a NOEL of 10 mg/kg bw/day. Skin penetration has been investigated in the rat in vivo. Sufficient information on tissue distribution and recovery is provided to assume that the results are acceptable. The percutaneous absorption study was performed with a 1.0 % formulation, where, in case of a semi-permanent hair dye, the foreseen use concentration is 2.0%. Comparing the NOEL with the maximum systemic exposure dose in humans indicates a safety margin of 476. A 147 was tested in bacterial cells for gene mutation in different experiments and gave positive results. The in vitro test for mammalian gene mutation assay is negative. The in vitro test for clastogenicity in human lymphocytes was negative but the study is considered inadequate. The in vivo UDS on rats hepatocytes is negative. The in vivo micronucleus test in mice gave negative results. Dihydroxyindoline HBr may be considered not","page":18,"pdf":"out_193.pdf","row_type":"noael_study","study_id":"out_193_noael_009"} |
| SCCNFP_vision_codex | NOAEL | =180 | mg/kg bw/day | rat | - | 4 weeks | NOAEL study | {"citation":"Ref. : 12 Guideline : OECD 408 Species/strain : Sprague-Dawley rat, Ico:OFA,SD (IOPs Caw) strain Group size : 5 males + 5 females 3 males+3 females (week 4, interim kill, test groups only","dose":"females and spleen weight was increased in both male and female high dose groups.","effect":"females and spleen weight was increased in both male and female high dose groups. After 4 weeks without treatment organ weights were comparable to controls. Histopathological changes were recorded in all treated animals but most notably at 180mg/kg bw/day. In particular discoloration within the kidney tubules and of the duodenum was reported in all treated groups with a dose-related increase in severity. These changes were also seen in treated animals at the end of the recovery period. The study did not identify a NOAEL. Ref. : 12 Guideline : OECD 408 Species/strain : Sprague-Dawley rat, Ico:OFA,SD (IOPs Caw) strain Group size : 5 males + 5 females 3 males+3 females (week 4, interim kill, test groups only) 5 males +5 females (week13-17 recovery groups, control + high dose) Test substance : SAT 930384 in aqueous solution Batch no : 4354/76 (purity 98.2%) Dose levels : 0, 5, 10 and 20 mg/kg bw/day in 5ml/kg pH2.5 Treatment period : 13 weeks + 4 week recovery GLP : in compliance Groups of 5 male and 5 female rats were dosed with the","page":7,"pdf":"out_193.pdf","row_type":"noael_study","study_id":"out_193_noael_001"} |
| SCCNFP_vision_codex | NOAEL | =20 | mg/kg bw/day | rat | - | - | NOAEL study | {"citation":"Ref. : 13","dose":"nt period there was a dose-related discoloration of urine at 10 and 20 mg/kg bw/day, which was more marked in the males.","effect":"nt period there was a dose-related discoloration of urine at 10 and 20 mg/kg bw/day, which was more marked in the males. After the recovery period, the urine colour of all treated animals was comparable to controls. Body weight gain and food consumption were comparable in all dose groups. There were no eye lesions. Microscopically, dose-related pigmentation was reported in the kidney tubules and duodenal villi of all treated rats, and was also present at the end of the recovery period. The study did not identify a NOAEL. No blood analyses were performed and therefore it is not possible to determine whether the observed pigmentation was associated with functional disturbances. Ref. : 13","page":7,"pdf":"out_193.pdf","row_type":"noael_study","study_id":"out_193_noael_002"} |
| SCCNFP_vision_codex | NOAEL | =10 | mg/kg/day | rat | dermal | Sub-chronic | repeated dose toxicity | {"citation":"Ref. : 19 2","dose":"ysiological background of brownish pigmentation, treatment-related exogenous pigments were found in kidneys of animals receiving doses of at least 20 mg/kg/day, with only occasional pigments found at the lowest dose (10 mg/kg/day).","effect":"ysiological background of brownish pigmentation, treatment-related exogenous pigments were found in kidneys of animals receiving doses of at least 20 mg/kg/day, with only occasional pigments found at the lowest dose (10 mg/kg/day). There were neither functional nor histological findings indicative for intestinal or renal injury, whether in treated or untreated animals. Due to the fact that if even minor signs of exogenous pigments were found in kidneys of rats dosed with 20 mg/kg/day, the no-observed effect-level (NOEL) was established at 10 mg/kg/day. Ref. : 19 2.3.8. Sub-chronic dermal toxicity No data 2.3.9. Sub-chronic inhalation toxicity No data","page":9,"pdf":"out_193.pdf","row_type":"noael_study","study_id":"out_193_noael_004"} |
| SCCNFP_vision_codex | NOAEL | =240 | mg/kg bw/day | rat | dermal | - | dermal absorption | {"citation":"Ref. : 15, 16 2","dose":"The mean numbers of corpora lutea, implantation sites, post-implantation loss, live foetuses and foetal body weights were similar for control and treated groups.","effect":"at it was not treatment-related. No abortions were observed. Food consumption and body weight gain were not affected by treatment. No macroscopic abnormalities were observed in any treatment group. The mean numbers of corpora lutea, implantation sites, post-implantation loss, live foetuses and foetal body weights were similar for control and treated groups. No treatment-related foetal malformations were observed. The only effect noted was generalised oedema in one foetus from a dam treated with 60mg/kg bw/day. The NOAEL for maternal toxicity and for embryo-foetal development was 240 mg/kg bw/day. Ref. : 15, 16 2.7. Toxicokinetics (incl. Percutaneous Absorption) 2.7.1 Percutaneous absorption in vivo Guideline : OECD 417 Species/strain : Sprague-Dawley rat, Him:OFA, SPF strain Group size : 6 females Route : Topical Test substance : 14C-labelled dihydroxyindoline (radiochemical purity >98%) Unlabelled material charge no: 1; SAT No. 920933 (purity not stated) Dose : 205 mg on 9 cm2 Exposure period : 30 minutes GLP : in compliance Lab","page":13,"pdf":"out_193.pdf","row_type":"noael_study","study_id":"out_193_noael_005"} |
| SCCNFP_vision_codex | NOAEL | =10 | mg/kg | rat | oral | 90 day | dermal absorption | {"dose":"Safety evaluation CALCULATION OF THE MARGIN OF SAFETY (Dihydroxyindoline HBr) (Air oxidative/semi-permanent) Based on a usage volume of 50 ml, containing at maximum 2 % Maximum absorption through the skin A (µg/cm2) = 1766 µg/cm2 Typical body weight of human = 60 kg Skin Area surface SAS (cm2) = 700 cm2 Dermal absorption per treatment SAS x A x...","effect":"_________________________________________________ 18/19 2.11. Safety evaluation CALCULATION OF THE MARGIN OF SAFETY (Dihydroxyindoline HBr) (Air oxidative/semi-permanent) Based on a usage volume of 50 ml, containing at maximum 2 % Maximum absorption through the skin A (µg/cm2) = 1766 µg/cm2 Typical body weight of human = 60 kg Skin Area surface SAS (cm2) = 700 cm2 Dermal absorption per treatment SAS x A x 0.001 = 1236 µg Systemic exposure dose (SED) SAS x A x 0.001/60 = 0.021 mg/kg No observed effect level (mg/kg) NOEL = 10 mg/kg (rat, 90 day, oral) Margin of Safety NOEL / SED = 476 2.12. Conclusions Insufficient information is provided on potential impurities. The database on toxicological properties is poor. Acute toxicity, irritation, sensitisation and embryotoxicity have been adequately investigated, following appropriate guidelines and GLP where relevant. It was irritant to the rabbit eye, but not skin when tested neat, and it is unlikely that similar results would occur under realistic conditions of use. It has shown sensi","page":18,"pdf":"out_193.pdf","row_type":"noael_study","study_id":"out_193_noael_006"} |
| SCCNFP_vision_codex | NOAEL | =10 | mg/kg bw/day | rat | oral | subchronic | repeated dose toxicity | {"dose":"Three subchronic oral dosing studies in rats indicate a NOEL of 10 mg/kg bw/day.","effect":"ies. The database on toxicological properties is poor. Acute toxicity, irritation, sensitisation and embryotoxicity have been adequately investigated, following appropriate guidelines and GLP where relevant. It was irritant to the rabbit eye, but not skin when tested neat, and it is unlikely that similar results would occur under realistic conditions of use. It has shown sensitising potential and formulations should be labelled with a warning in this respect. Three subchronic oral dosing studies in rats indicate a NOEL of 10 mg/kg bw/day. Skin penetration has been investigated in the rat in vivo. Sufficient information on tissue distribution and recovery is provided to assume that the results are acceptable. The percutaneous absorption study was performed with a 1.0 % formulation, where, in case of a semi-permanent hair dye, the foreseen use concentration is 2.0%. Comparing the NOEL with the maximum systemic exposure dose in humans indicates a safety margin of 476. A 147 was tested in bacterial cells for gene mutation in differe","page":18,"pdf":"out_193.pdf","row_type":"noael_study","study_id":"out_193_noael_008"} |
| SCCNFP_vision_codex | NOAEL | =2 | % | rat | oral | subchronic | repeated dose toxicity | {"dose":"Three subchronic oral dosing studies in rats indicate a NOEL of 10 mg/kg bw/day.","effect":"wn sensitising potential and formulations should be labelled with a warning in this respect. Three subchronic oral dosing studies in rats indicate a NOEL of 10 mg/kg bw/day. Skin penetration has been investigated in the rat in vivo. Sufficient information on tissue distribution and recovery is provided to assume that the results are acceptable. The percutaneous absorption study was performed with a 1.0 % formulation, where, in case of a semi-permanent hair dye, the foreseen use concentration is 2.0%. Comparing the NOEL with the maximum systemic exposure dose in humans indicates a safety margin of 476. A 147 was tested in bacterial cells for gene mutation in different experiments and gave positive results. The in vitro test for mammalian gene mutation assay is negative. The in vitro test for clastogenicity in human lymphocytes was negative but the study is considered inadequate. The in vivo UDS on rats hepatocytes is negative. The in vivo micronucleus test in mice gave negative results. Dihydroxyindoline HBr may be considered not","page":18,"pdf":"out_193.pdf","row_type":"noael_study","study_id":"out_193_noael_009"} |
| SCCNFP_vision_codex | NOAEL | =180 | mg/kg bw/day | rat | - | 4 weeks | NOAEL study | {"citation":"Ref. : 12 Guideline : OECD 408 Species/strain : Sprague-Dawley rat, Ico:OFA,SD (IOPs Caw) strain Group size : 5 males + 5 females 3 males+3 females (week 4, interim kill, test groups only","dose":"females and spleen weight was increased in both male and female high dose groups.","effect":"females and spleen weight was increased in both male and female high dose groups. After 4 weeks without treatment organ weights were comparable to controls. Histopathological changes were recorded in all treated animals but most notably at 180mg/kg bw/day. In particular discoloration within the kidney tubules and of the duodenum was reported in all treated groups with a dose-related increase in severity. These changes were also seen in treated animals at the end of the recovery period. The study did not identify a NOAEL. Ref. : 12 Guideline : OECD 408 Species/strain : Sprague-Dawley rat, Ico:OFA,SD (IOPs Caw) strain Group size : 5 males + 5 females 3 males+3 females (week 4, interim kill, test groups only) 5 males +5 females (week13-17 recovery groups, control + high dose) Test substance : SAT 930384 in aqueous solution Batch no : 4354/76 (purity 98.2%) Dose levels : 0, 5, 10 and 20 mg/kg bw/day in 5ml/kg pH2.5 Treatment period : 13 weeks + 4 week recovery GLP : in compliance Groups of 5 male and 5 female rats were dosed with the","page":7,"pdf":"out_193.pdf","row_type":"noael_study","study_id":"out_193_noael_001"} |
| SCCNFP_vision_codex | NOAEL | =20 | mg/kg bw/day | rat | - | - | NOAEL study | {"citation":"Ref. : 13","dose":"nt period there was a dose-related discoloration of urine at 10 and 20 mg/kg bw/day, which was more marked in the males.","effect":"nt period there was a dose-related discoloration of urine at 10 and 20 mg/kg bw/day, which was more marked in the males. After the recovery period, the urine colour of all treated animals was comparable to controls. Body weight gain and food consumption were comparable in all dose groups. There were no eye lesions. Microscopically, dose-related pigmentation was reported in the kidney tubules and duodenal villi of all treated rats, and was also present at the end of the recovery period. The study did not identify a NOAEL. No blood analyses were performed and therefore it is not possible to determine whether the observed pigmentation was associated with functional disturbances. Ref. : 13","page":7,"pdf":"out_193.pdf","row_type":"noael_study","study_id":"out_193_noael_002"} |
| SCCNFP_vision_codex | NOAEL | =10 | mg/kg/day | rat | dermal | Sub-chronic | repeated dose toxicity | {"citation":"Ref. : 19 2","dose":"ysiological background of brownish pigmentation, treatment-related exogenous pigments were found in kidneys of animals receiving doses of at least 20 mg/kg/day, with only occasional pigments found at the lowest dose (10 mg/kg/day).","effect":"ysiological background of brownish pigmentation, treatment-related exogenous pigments were found in kidneys of animals receiving doses of at least 20 mg/kg/day, with only occasional pigments found at the lowest dose (10 mg/kg/day). There were neither functional nor histological findings indicative for intestinal or renal injury, whether in treated or untreated animals. Due to the fact that if even minor signs of exogenous pigments were found in kidneys of rats dosed with 20 mg/kg/day, the no-observed effect-level (NOEL) was established at 10 mg/kg/day. Ref. : 19 2.3.8. Sub-chronic dermal toxicity No data 2.3.9. Sub-chronic inhalation toxicity No data","page":9,"pdf":"out_193.pdf","row_type":"noael_study","study_id":"out_193_noael_004"} |
| SCCNFP_vision_codex | NOAEL | =240 | mg/kg bw/day | rat | dermal | - | dermal absorption | {"citation":"Ref. : 15, 16 2","dose":"The mean numbers of corpora lutea, implantation sites, post-implantation loss, live foetuses and foetal body weights were similar for control and treated groups.","effect":"at it was not treatment-related. No abortions were observed. Food consumption and body weight gain were not affected by treatment. No macroscopic abnormalities were observed in any treatment group. The mean numbers of corpora lutea, implantation sites, post-implantation loss, live foetuses and foetal body weights were similar for control and treated groups. No treatment-related foetal malformations were observed. The only effect noted was generalised oedema in one foetus from a dam treated with 60mg/kg bw/day. The NOAEL for maternal toxicity and for embryo-foetal development was 240 mg/kg bw/day. Ref. : 15, 16 2.7. Toxicokinetics (incl. Percutaneous Absorption) 2.7.1 Percutaneous absorption in vivo Guideline : OECD 417 Species/strain : Sprague-Dawley rat, Him:OFA, SPF strain Group size : 6 females Route : Topical Test substance : 14C-labelled dihydroxyindoline (radiochemical purity >98%) Unlabelled material charge no: 1; SAT No. 920933 (purity not stated) Dose : 205 mg on 9 cm2 Exposure period : 30 minutes GLP : in compliance Lab","page":13,"pdf":"out_193.pdf","row_type":"noael_study","study_id":"out_193_noael_005"} |
| SCCNFP_vision_codex | NOAEL | =10 | mg/kg | rat | oral | 90 day | dermal absorption | {"dose":"Safety evaluation CALCULATION OF THE MARGIN OF SAFETY (Dihydroxyindoline HBr) (Air oxidative/semi-permanent) Based on a usage volume of 50 ml, containing at maximum 2 % Maximum absorption through the skin A (µg/cm2) = 1766 µg/cm2 Typical body weight of human = 60 kg Skin Area surface SAS (cm2) = 700 cm2 Dermal absorption per treatment SAS x A x...","effect":"_________________________________________________ 18/19 2.11. Safety evaluation CALCULATION OF THE MARGIN OF SAFETY (Dihydroxyindoline HBr) (Air oxidative/semi-permanent) Based on a usage volume of 50 ml, containing at maximum 2 % Maximum absorption through the skin A (µg/cm2) = 1766 µg/cm2 Typical body weight of human = 60 kg Skin Area surface SAS (cm2) = 700 cm2 Dermal absorption per treatment SAS x A x 0.001 = 1236 µg Systemic exposure dose (SED) SAS x A x 0.001/60 = 0.021 mg/kg No observed effect level (mg/kg) NOEL = 10 mg/kg (rat, 90 day, oral) Margin of Safety NOEL / SED = 476 2.12. Conclusions Insufficient information is provided on potential impurities. The database on toxicological properties is poor. Acute toxicity, irritation, sensitisation and embryotoxicity have been adequately investigated, following appropriate guidelines and GLP where relevant. It was irritant to the rabbit eye, but not skin when tested neat, and it is unlikely that similar results would occur under realistic conditions of use. It has shown sensi","page":18,"pdf":"out_193.pdf","row_type":"noael_study","study_id":"out_193_noael_006"} |
| SCCNFP_vision_codex | NOAEL | =10 | mg/kg bw/day | rat | oral | subchronic | repeated dose toxicity | {"dose":"Three subchronic oral dosing studies in rats indicate a NOEL of 10 mg/kg bw/day.","effect":"ies. The database on toxicological properties is poor. Acute toxicity, irritation, sensitisation and embryotoxicity have been adequately investigated, following appropriate guidelines and GLP where relevant. It was irritant to the rabbit eye, but not skin when tested neat, and it is unlikely that similar results would occur under realistic conditions of use. It has shown sensitising potential and formulations should be labelled with a warning in this respect. Three subchronic oral dosing studies in rats indicate a NOEL of 10 mg/kg bw/day. Skin penetration has been investigated in the rat in vivo. Sufficient information on tissue distribution and recovery is provided to assume that the results are acceptable. The percutaneous absorption study was performed with a 1.0 % formulation, where, in case of a semi-permanent hair dye, the foreseen use concentration is 2.0%. Comparing the NOEL with the maximum systemic exposure dose in humans indicates a safety margin of 476. A 147 was tested in bacterial cells for gene mutation in differe","page":18,"pdf":"out_193.pdf","row_type":"noael_study","study_id":"out_193_noael_008"} |
| SCCNFP_vision_codex | NOAEL | =2 | % | rat | oral | subchronic | repeated dose toxicity | {"dose":"Three subchronic oral dosing studies in rats indicate a NOEL of 10 mg/kg bw/day.","effect":"wn sensitising potential and formulations should be labelled with a warning in this respect. Three subchronic oral dosing studies in rats indicate a NOEL of 10 mg/kg bw/day. Skin penetration has been investigated in the rat in vivo. Sufficient information on tissue distribution and recovery is provided to assume that the results are acceptable. The percutaneous absorption study was performed with a 1.0 % formulation, where, in case of a semi-permanent hair dye, the foreseen use concentration is 2.0%. Comparing the NOEL with the maximum systemic exposure dose in humans indicates a safety margin of 476. A 147 was tested in bacterial cells for gene mutation in different experiments and gave positive results. The in vitro test for mammalian gene mutation assay is negative. The in vitro test for clastogenicity in human lymphocytes was negative but the study is considered inadequate. The in vivo UDS on rats hepatocytes is negative. The in vivo micronucleus test in mice gave negative results. Dihydroxyindoline HBr may be considered not","page":18,"pdf":"out_193.pdf","row_type":"noael_study","study_id":"out_193_noael_009"} |
| SCCNFP_vision_codex | NOAEL | =180 | mg/kg bw/day | rat | - | 4 weeks | NOAEL study | {"citation":"Ref. : 12 Guideline : OECD 408 Species/strain : Sprague-Dawley rat, Ico:OFA,SD (IOPs Caw) strain Group size : 5 males + 5 females 3 males+3 females (week 4, interim kill, test groups only","dose":"females and spleen weight was increased in both male and female high dose groups.","effect":"females and spleen weight was increased in both male and female high dose groups. After 4 weeks without treatment organ weights were comparable to controls. Histopathological changes were recorded in all treated animals but most notably at 180mg/kg bw/day. In particular discoloration within the kidney tubules and of the duodenum was reported in all treated groups with a dose-related increase in severity. These changes were also seen in treated animals at the end of the recovery period. The study did not identify a NOAEL. Ref. : 12 Guideline : OECD 408 Species/strain : Sprague-Dawley rat, Ico:OFA,SD (IOPs Caw) strain Group size : 5 males + 5 females 3 males+3 females (week 4, interim kill, test groups only) 5 males +5 females (week13-17 recovery groups, control + high dose) Test substance : SAT 930384 in aqueous solution Batch no : 4354/76 (purity 98.2%) Dose levels : 0, 5, 10 and 20 mg/kg bw/day in 5ml/kg pH2.5 Treatment period : 13 weeks + 4 week recovery GLP : in compliance Groups of 5 male and 5 female rats were dosed with the","page":7,"pdf":"out_193.pdf","row_type":"noael_study","study_id":"out_193_noael_001"} |
| SCCNFP_vision_codex | NOAEL | =20 | mg/kg bw/day | rat | - | - | NOAEL study | {"citation":"Ref. : 13","dose":"nt period there was a dose-related discoloration of urine at 10 and 20 mg/kg bw/day, which was more marked in the males.","effect":"nt period there was a dose-related discoloration of urine at 10 and 20 mg/kg bw/day, which was more marked in the males. After the recovery period, the urine colour of all treated animals was comparable to controls. Body weight gain and food consumption were comparable in all dose groups. There were no eye lesions. Microscopically, dose-related pigmentation was reported in the kidney tubules and duodenal villi of all treated rats, and was also present at the end of the recovery period. The study did not identify a NOAEL. No blood analyses were performed and therefore it is not possible to determine whether the observed pigmentation was associated with functional disturbances. Ref. : 13","page":7,"pdf":"out_193.pdf","row_type":"noael_study","study_id":"out_193_noael_002"} |
| SCCNFP_vision_codex | NOAEL | =10 | mg/kg/day | rat | dermal | Sub-chronic | repeated dose toxicity | {"citation":"Ref. : 19 2","dose":"ysiological background of brownish pigmentation, treatment-related exogenous pigments were found in kidneys of animals receiving doses of at least 20 mg/kg/day, with only occasional pigments found at the lowest dose (10 mg/kg/day).","effect":"ysiological background of brownish pigmentation, treatment-related exogenous pigments were found in kidneys of animals receiving doses of at least 20 mg/kg/day, with only occasional pigments found at the lowest dose (10 mg/kg/day). There were neither functional nor histological findings indicative for intestinal or renal injury, whether in treated or untreated animals. Due to the fact that if even minor signs of exogenous pigments were found in kidneys of rats dosed with 20 mg/kg/day, the no-observed effect-level (NOEL) was established at 10 mg/kg/day. Ref. : 19 2.3.8. Sub-chronic dermal toxicity No data 2.3.9. Sub-chronic inhalation toxicity No data","page":9,"pdf":"out_193.pdf","row_type":"noael_study","study_id":"out_193_noael_004"} |
| SCCNFP_vision_codex | NOAEL | =240 | mg/kg bw/day | rat | dermal | - | dermal absorption | {"citation":"Ref. : 15, 16 2","dose":"The mean numbers of corpora lutea, implantation sites, post-implantation loss, live foetuses and foetal body weights were similar for control and treated groups.","effect":"at it was not treatment-related. No abortions were observed. Food consumption and body weight gain were not affected by treatment. No macroscopic abnormalities were observed in any treatment group. The mean numbers of corpora lutea, implantation sites, post-implantation loss, live foetuses and foetal body weights were similar for control and treated groups. No treatment-related foetal malformations were observed. The only effect noted was generalised oedema in one foetus from a dam treated with 60mg/kg bw/day. The NOAEL for maternal toxicity and for embryo-foetal development was 240 mg/kg bw/day. Ref. : 15, 16 2.7. Toxicokinetics (incl. Percutaneous Absorption) 2.7.1 Percutaneous absorption in vivo Guideline : OECD 417 Species/strain : Sprague-Dawley rat, Him:OFA, SPF strain Group size : 6 females Route : Topical Test substance : 14C-labelled dihydroxyindoline (radiochemical purity >98%) Unlabelled material charge no: 1; SAT No. 920933 (purity not stated) Dose : 205 mg on 9 cm2 Exposure period : 30 minutes GLP : in compliance Lab","page":13,"pdf":"out_193.pdf","row_type":"noael_study","study_id":"out_193_noael_005"} |
| SCCNFP_vision_codex | NOAEL | =10 | mg/kg | rat | oral | 90 day | dermal absorption | {"dose":"Safety evaluation CALCULATION OF THE MARGIN OF SAFETY (Dihydroxyindoline HBr) (Air oxidative/semi-permanent) Based on a usage volume of 50 ml, containing at maximum 2 % Maximum absorption through the skin A (µg/cm2) = 1766 µg/cm2 Typical body weight of human = 60 kg Skin Area surface SAS (cm2) = 700 cm2 Dermal absorption per treatment SAS x A x...","effect":"_________________________________________________ 18/19 2.11. Safety evaluation CALCULATION OF THE MARGIN OF SAFETY (Dihydroxyindoline HBr) (Air oxidative/semi-permanent) Based on a usage volume of 50 ml, containing at maximum 2 % Maximum absorption through the skin A (µg/cm2) = 1766 µg/cm2 Typical body weight of human = 60 kg Skin Area surface SAS (cm2) = 700 cm2 Dermal absorption per treatment SAS x A x 0.001 = 1236 µg Systemic exposure dose (SED) SAS x A x 0.001/60 = 0.021 mg/kg No observed effect level (mg/kg) NOEL = 10 mg/kg (rat, 90 day, oral) Margin of Safety NOEL / SED = 476 2.12. Conclusions Insufficient information is provided on potential impurities. The database on toxicological properties is poor. Acute toxicity, irritation, sensitisation and embryotoxicity have been adequately investigated, following appropriate guidelines and GLP where relevant. It was irritant to the rabbit eye, but not skin when tested neat, and it is unlikely that similar results would occur under realistic conditions of use. It has shown sensi","page":18,"pdf":"out_193.pdf","row_type":"noael_study","study_id":"out_193_noael_006"} |
| SCCNFP_vision_codex | NOAEL | =10 | mg/kg bw/day | rat | oral | subchronic | repeated dose toxicity | {"dose":"Three subchronic oral dosing studies in rats indicate a NOEL of 10 mg/kg bw/day.","effect":"ies. The database on toxicological properties is poor. Acute toxicity, irritation, sensitisation and embryotoxicity have been adequately investigated, following appropriate guidelines and GLP where relevant. It was irritant to the rabbit eye, but not skin when tested neat, and it is unlikely that similar results would occur under realistic conditions of use. It has shown sensitising potential and formulations should be labelled with a warning in this respect. Three subchronic oral dosing studies in rats indicate a NOEL of 10 mg/kg bw/day. Skin penetration has been investigated in the rat in vivo. Sufficient information on tissue distribution and recovery is provided to assume that the results are acceptable. The percutaneous absorption study was performed with a 1.0 % formulation, where, in case of a semi-permanent hair dye, the foreseen use concentration is 2.0%. Comparing the NOEL with the maximum systemic exposure dose in humans indicates a safety margin of 476. A 147 was tested in bacterial cells for gene mutation in differe","page":18,"pdf":"out_193.pdf","row_type":"noael_study","study_id":"out_193_noael_008"} |
| SCCNFP_vision_codex | NOAEL | =2 | % | rat | oral | subchronic | repeated dose toxicity | {"dose":"Three subchronic oral dosing studies in rats indicate a NOEL of 10 mg/kg bw/day.","effect":"wn sensitising potential and formulations should be labelled with a warning in this respect. Three subchronic oral dosing studies in rats indicate a NOEL of 10 mg/kg bw/day. Skin penetration has been investigated in the rat in vivo. Sufficient information on tissue distribution and recovery is provided to assume that the results are acceptable. The percutaneous absorption study was performed with a 1.0 % formulation, where, in case of a semi-permanent hair dye, the foreseen use concentration is 2.0%. Comparing the NOEL with the maximum systemic exposure dose in humans indicates a safety margin of 476. A 147 was tested in bacterial cells for gene mutation in different experiments and gave positive results. The in vitro test for mammalian gene mutation assay is negative. The in vitro test for clastogenicity in human lymphocytes was negative but the study is considered inadequate. The in vivo UDS on rats hepatocytes is negative. The in vivo micronucleus test in mice gave negative results. Dihydroxyindoline HBr may be considered not","page":18,"pdf":"out_193.pdf","row_type":"noael_study","study_id":"out_193_noael_009"} |
UnifiedCodex:SCCNFP:beta.noael_studies 9 endpoints
| Source | Endpoint Type | Value | Unit | Species | Route | Duration | Study Type | Reference |
|---|---|---|---|---|---|---|---|---|
| UnifiedCodex:SCCNFP:beta.noael_studies | - | 180 | mg/kg bw/day | rat | - | 4 weeks | - | SOURCE_SUBDIR=out_193; REPORT_TITLE=OPINION OF THE SCIENTIFIC COMMITTEE ON COSMETIC PRODUCTS AND NON-FOOD PRODUCTS INTENDED FOR CONSUMERS CONCERNING DIHYDROXYINDOLINE HBR COLIPA n° : A147; OPINION_NUMBER=SCCNFP/0669/03; COMMITTEE=SCCNFP; REPORT_DATE=18 March 2003; VALUE_TEXT=180; DOSE=females and spleen weight was increased in both male and female high dose groups.; EFFECT=females and spleen weight was increased in both male and female high dose groups. After 4 weeks without treatment organ weights were comparable to controls. Histopathological changes were recorded in all treated animals but most notably at 180mg/kg bw/day. In particular discoloration within the kidney tubules and of the duodenum was reported in all treated groups with a dose-related increase in severity. These changes were also seen in treated animals at the end of the recovery period. The study did not identify a NOAEL. Ref. : 12 Guideline : OECD 408 Species/strain : Sprague-Dawley rat, Ico:OFA,SD (IOPs Caw) strain Group size : 5 males + 5 females 3 males+3 females (week 4, interim kill, test groups only) 5 males +5 females (week13-17 recovery groups, control + high dose) Test substance : SAT 930384 in aqueous solution Batch no : 4354/76 (purity 98.2%) Dose levels : 0, 5, 10 and 20 mg/kg bw/day in 5ml/kg pH2.5 Treatment period : 13 weeks + 4 week recovery GLP : in compliance Groups of 5 male and 5 female rats were dosed with the; CITATION=Ref. : 12 Guideline : OECD 408 Species/strain : Sprague-Dawley rat, Ico:OFA,SD (IOPs Caw) strain Group size : 5 males + 5 females 3 males+3 females (week 4, interim kill, test groups only; CITATION_NUMBERS=[12,408,5,3,4]; REFERENCE=Ref. : 12 Guideline : OECD 408 Species/strain : Sprague-Dawley rat, Ico:OFA,SD (IOPs Caw) strain Group size : 5 males + 5 females 3 males+3 females (week 4, interim kill, test groups only; DETAILS_JSON={"cas_number":"29539-03-5","citation":"Ref. : 12 Guideline : OECD 408 Species/strain : Sprague-Dawley rat, Ico:OFA,SD (IOPs Caw) strain Group size : 5 males + 5 females 3 males+3 females (week 4, interim kill, test groups only","dose":"females and spleen weight was increased in both male and female high dose groups.","duration":"4 weeks","effect":"females and spleen weight was increased in both male and female high dose groups. After 4 weeks without treatment organ weights were comparable to controls. Histopathological changes were recorded in all treated animals but most notably at 180mg/kg bw/day. In particular discoloration within the kidney tubules and of the duodenum was reported in all treated groups with a dose-related increase in severity. These changes were also seen in treated animals at the end of the recovery period. The study did not identify a NOAEL. Ref. : 12 Guideline : OECD 408 Species/strain : Sprague-Dawley rat, Ico:OFA,SD (IOPs Caw) strain Group size : 5 males + 5 females 3 males+3 females (week 4, interim kill, test groups only) 5 males +5 females (week13-17 recovery groups, control + high dose) Test substance : SAT 930384 in aqueous solution Batch no : 4354/76 (purity 98.2%) Dose levels : 0, 5, 10 and 20 mg/kg bw/day in 5ml/kg pH2.5 Treatment period : 13 weeks + 4 week recovery GLP : in compliance Groups of 5 male and 5 female rats were dosed with the","endpoint":"","ingredient":"5,6-Dihydroxy indoline x HBr","loael_value":"","noael_unit":"mg/kg bw/day","noael_value":"180","page":7,"route":"","species":"rat","study_id":"out_193_noael_001"} |
| UnifiedCodex:SCCNFP:beta.noael_studies | - | 20 | mg/kg bw/day | rat | - | - | - | SOURCE_SUBDIR=out_193; REPORT_TITLE=OPINION OF THE SCIENTIFIC COMMITTEE ON COSMETIC PRODUCTS AND NON-FOOD PRODUCTS INTENDED FOR CONSUMERS CONCERNING DIHYDROXYINDOLINE HBR COLIPA n° : A147; OPINION_NUMBER=SCCNFP/0669/03; COMMITTEE=SCCNFP; REPORT_DATE=18 March 2003; VALUE_TEXT=20; DOSE=nt period there was a dose-related discoloration of urine at 10 and 20 mg/kg bw/day, which was more marked in the males.; EFFECT=nt period there was a dose-related discoloration of urine at 10 and 20 mg/kg bw/day, which was more marked in the males. After the recovery period, the urine colour of all treated animals was comparable to controls. Body weight gain and food consumption were comparable in all dose groups. There were no eye lesions. Microscopically, dose-related pigmentation was reported in the kidney tubules and duodenal villi of all treated rats, and was also present at the end of the recovery period. The study did not identify a NOAEL. No blood analyses were performed and therefore it is not possible to determine whether the observed pigmentation was associated with functional disturbances. Ref. : 13; CITATION=Ref. : 13; CITATION_NUMBERS=[13]; REFERENCE=Ref. : 13; DETAILS_JSON={"cas_number":"29539-03-5","citation":"Ref. : 13","dose":"nt period there was a dose-related discoloration of urine at 10 and 20 mg/kg bw/day, which was more marked in the males.","duration":"","effect":"nt period there was a dose-related discoloration of urine at 10 and 20 mg/kg bw/day, which was more marked in the males. After the recovery period, the urine colour of all treated animals was comparable to controls. Body weight gain and food consumption were comparable in all dose groups. There were no eye lesions. Microscopically, dose-related pigmentation was reported in the kidney tubules and duodenal villi of all treated rats, and was also present at the end of the recovery period. The study did not identify a NOAEL. No blood analyses were performed and therefore it is not possible to determine whether the observed pigmentation was associated with functional disturbances. Ref. : 13","endpoint":"","ingredient":"5,6-Dihydroxy indoline x HBr","loael_value":"","noael_unit":"mg/kg bw/day","noael_value":"20","page":7,"route":"","species":"rat","study_id":"out_193_noael_002"} |
| UnifiedCodex:SCCNFP:beta.noael_studies | - | 20 | mg/kg bw/day | rat | - | - | - | SOURCE_SUBDIR=out_193; REPORT_TITLE=OPINION OF THE SCIENTIFIC COMMITTEE ON COSMETIC PRODUCTS AND NON-FOOD PRODUCTS INTENDED FOR CONSUMERS CONCERNING DIHYDROXYINDOLINE HBR COLIPA n° : A147; OPINION_NUMBER=SCCNFP/0669/03; COMMITTEE=SCCNFP; REPORT_DATE=18 March 2003; VALUE_TEXT=20; DOSE=Four of 15 high dose males exhibited significantly elevated blood levels of creatinine at the week 7 sampling.; EFFECT=l transferase, N-acetyl--glucosamidase, urea, creatinine, bilirubin, glucose, proteins and ketones showed no consistent changes and were within the range of control levels. Four of 15 high dose males exhibited significantly elevated blood levels of creatinine at the week 7 sampling. In the absence of similar effects at other times, this was considered to be of doubtful toxicological significance. Blood urea was similar to controls at all times and doses. The authors concluded that the dose of 20mg/kg bw/day was a NOAEL, but this requires clarification. Ref. : 14 Dihydroxyindoline is an indol derivative with chemical similarities to melanin precursors. Brownish pigments occur frequently in rodent’s (rats) kidneys representing e.g. lipofuscine, hemosiderine or even α2µ-globulin-containing inclusions – all appearing as “brownish pigment”. At a request of the SCCNFP, industry further investigated the brownish pigment observed in the organ slides of the duodenum and in the kidneys as well as their potential biological importance. The; CITATION=Ref. : 14 Dihydroxyindoline is an indol derivative with chemical similarities to melanin precursors; CITATION_NUMBERS=[14]; REFERENCE=Ref. : 14 Dihydroxyindoline is an indol derivative with chemical similarities to melanin precursors; DETAILS_JSON={"cas_number":"29539-03-5","citation":"Ref. : 14 Dihydroxyindoline is an indol derivative with chemical similarities to melanin precursors","dose":"Four of 15 high dose males exhibited significantly elevated blood levels of creatinine at the week 7 sampling.","duration":"","effect":"l transferase, N-acetyl-\u0003-glucosamidase, urea, creatinine, bilirubin, glucose, proteins and ketones showed no consistent changes and were within the range of control levels. Four of 15 high dose males exhibited significantly elevated blood levels of creatinine at the week 7 sampling. In the absence of similar effects at other times, this was considered to be of doubtful toxicological significance. Blood urea was similar to controls at all times and doses. The authors concluded that the dose of 20mg/kg bw/day was a NOAEL, but this requires clarification. Ref. : 14 Dihydroxyindoline is an indol derivative with chemical similarities to melanin precursors. Brownish pigments occur frequently in rodent’s (rats) kidneys representing e.g. lipofuscine, hemosiderine or even α2µ-globulin-containing inclusions – all appearing as “brownish pigment”. At a request of the SCCNFP, industry further investigated the brownish pigment observed in the organ slides of the duodenum and in the kidneys as well as their potential biological importance. The","endpoint":"","ingredient":"5,6-Dihydroxy indoline x HBr","loael_value":"","noael_unit":"mg/kg bw/day","noael_value":"20","page":8,"route":"","species":"rat","study_id":"out_193_noael_003"} |
| UnifiedCodex:SCCNFP:beta.noael_studies | dermal absorption | 240 | mg/kg bw/day | rat | dermal | - | dermal absorption | SOURCE_SUBDIR=out_193; REPORT_TITLE=OPINION OF THE SCIENTIFIC COMMITTEE ON COSMETIC PRODUCTS AND NON-FOOD PRODUCTS INTENDED FOR CONSUMERS CONCERNING DIHYDROXYINDOLINE HBR COLIPA n° : A147; OPINION_NUMBER=SCCNFP/0669/03; COMMITTEE=SCCNFP; REPORT_DATE=18 March 2003; VALUE_TEXT=240; DOSE=The mean numbers of corpora lutea, implantation sites, post-implantation loss, live foetuses and foetal body weights were similar for control and treated groups.; EFFECT=at it was not treatment-related. No abortions were observed. Food consumption and body weight gain were not affected by treatment. No macroscopic abnormalities were observed in any treatment group. The mean numbers of corpora lutea, implantation sites, post-implantation loss, live foetuses and foetal body weights were similar for control and treated groups. No treatment-related foetal malformations were observed. The only effect noted was generalised oedema in one foetus from a dam treated with 60mg/kg bw/day. The NOAEL for maternal toxicity and for embryo-foetal development was 240 mg/kg bw/day. Ref. : 15, 16 2.7. Toxicokinetics (incl. Percutaneous Absorption) 2.7.1 Percutaneous absorption in vivo Guideline : OECD 417 Species/strain : Sprague-Dawley rat, Him:OFA, SPF strain Group size : 6 females Route : Topical Test substance : 14C-labelled dihydroxyindoline (radiochemical purity >98%) Unlabelled material charge no: 1; SAT No. 920933 (purity not stated) Dose : 205 mg on 9 cm2 Exposure period : 30 minutes GLP : in compliance Lab; CITATION=Ref. : 15, 16 2; CITATION_NUMBERS=[15,16,2]; REFERENCE=Ref. : 15, 16 2; DETAILS_JSON={"cas_number":"29539-03-5","citation":"Ref. : 15, 16 2","dose":"The mean numbers of corpora lutea, implantation sites, post-implantation loss, live foetuses and foetal body weights were similar for control and treated groups.","duration":"","effect":"at it was not treatment-related. No abortions were observed. Food consumption and body weight gain were not affected by treatment. No macroscopic abnormalities were observed in any treatment group. The mean numbers of corpora lutea, implantation sites, post-implantation loss, live foetuses and foetal body weights were similar for control and treated groups. No treatment-related foetal malformations were observed. The only effect noted was generalised oedema in one foetus from a dam treated with 60mg/kg bw/day. The NOAEL for maternal toxicity and for embryo-foetal development was 240 mg/kg bw/day. Ref. : 15, 16 2.7. Toxicokinetics (incl. Percutaneous Absorption) 2.7.1 Percutaneous absorption in vivo Guideline : OECD 417 Species/strain : Sprague-Dawley rat, Him:OFA, SPF strain Group size : 6 females Route : Topical Test substance : 14C-labelled dihydroxyindoline (radiochemical purity >98%) Unlabelled material charge no: 1; SAT No. 920933 (purity not stated) Dose : 205 mg on 9 cm2 Exposure period : 30 minutes GLP : in compliance Lab","endpoint":"dermal absorption","ingredient":"5,6-Dihydroxy indoline x HBr","loael_value":"","noael_unit":"mg/kg bw/day","noael_value":"240","page":13,"route":"dermal","species":"rat","study_id":"out_193_noael_005"} |
| UnifiedCodex:SCCNFP:beta.noael_studies | dermal absorption | =10 | mg/kg | rat | oral | 90 day | dermal absorption | SOURCE_SUBDIR=out_193; REPORT_TITLE=OPINION OF THE SCIENTIFIC COMMITTEE ON COSMETIC PRODUCTS AND NON-FOOD PRODUCTS INTENDED FOR CONSUMERS CONCERNING DIHYDROXYINDOLINE HBR COLIPA n° : A147; OPINION_NUMBER=SCCNFP/0669/03; COMMITTEE=SCCNFP; REPORT_DATE=18 March 2003; VALUE_TEXT== 10; DOSE=Safety evaluation CALCULATION OF THE MARGIN OF SAFETY (Dihydroxyindoline HBr) (Air oxidative/semi-permanent) Based on a usage volume of 50 ml, containing at maximum 2 % Maximum absorption through the skin A (µg/cm2) = 1766 µg/cm2 Typical body weight of human = 60 kg Skin Area surface SAS (cm2) = 700 cm2 Dermal absorption per treatment SAS x A x...; EFFECT=_________________________________________________ 18/19 2.11. Safety evaluation CALCULATION OF THE MARGIN OF SAFETY (Dihydroxyindoline HBr) (Air oxidative/semi-permanent) Based on a usage volume of 50 ml, containing at maximum 2 % Maximum absorption through the skin A (µg/cm2) = 1766 µg/cm2 Typical body weight of human = 60 kg Skin Area surface SAS (cm2) = 700 cm2 Dermal absorption per treatment SAS x A x 0.001 = 1236 µg Systemic exposure dose (SED) SAS x A x 0.001/60 = 0.021 mg/kg No observed effect level (mg/kg) NOEL = 10 mg/kg (rat, 90 day, oral) Margin of Safety NOEL / SED = 476 2.12. Conclusions Insufficient information is provided on potential impurities. The database on toxicological properties is poor. Acute toxicity, irritation, sensitisation and embryotoxicity have been adequately investigated, following appropriate guidelines and GLP where relevant. It was irritant to the rabbit eye, but not skin when tested neat, and it is unlikely that similar results would occur under realistic conditions of use. It has shown sensi; CITATION_NUMBERS=[]; DETAILS_JSON={"cas_number":"29539-03-5","citation":"","dose":"Safety evaluation CALCULATION OF THE MARGIN OF SAFETY (Dihydroxyindoline HBr) (Air oxidative/semi-permanent) Based on a usage volume of 50 ml, containing at maximum 2 % Maximum absorption through the skin A (µg/cm2) = 1766 µg/cm2 Typical body weight of human = 60 kg Skin Area surface SAS (cm2) = 700 cm2 Dermal absorption per treatment SAS x A x...","duration":"90 day","effect":"_________________________________________________ 18/19 2.11. Safety evaluation CALCULATION OF THE MARGIN OF SAFETY (Dihydroxyindoline HBr) (Air oxidative/semi-permanent) Based on a usage volume of 50 ml, containing at maximum 2 % Maximum absorption through the skin A (µg/cm2) = 1766 µg/cm2 Typical body weight of human = 60 kg Skin Area surface SAS (cm2) = 700 cm2 Dermal absorption per treatment SAS x A x 0.001 = 1236 µg Systemic exposure dose (SED) SAS x A x 0.001/60 = 0.021 mg/kg No observed effect level (mg/kg) NOEL = 10 mg/kg (rat, 90 day, oral) Margin of Safety NOEL / SED = 476 2.12. Conclusions Insufficient information is provided on potential impurities. The database on toxicological properties is poor. Acute toxicity, irritation, sensitisation and embryotoxicity have been adequately investigated, following appropriate guidelines and GLP where relevant. It was irritant to the rabbit eye, but not skin when tested neat, and it is unlikely that similar results would occur under realistic conditions of use. It has shown sensi","endpoint":"dermal absorption","ingredient":"5,6-Dihydroxy indoline x HBr","loael_value":"","noael_unit":"mg/kg","noael_value":"= 10","page":18,"route":"oral","species":"rat","study_id":"out_193_noael_006"} |
| UnifiedCodex:SCCNFP:beta.noael_studies | dermal absorption | =10 | mg/kg | rat | oral | 90 day | dermal absorption | SOURCE_SUBDIR=out_193; REPORT_TITLE=OPINION OF THE SCIENTIFIC COMMITTEE ON COSMETIC PRODUCTS AND NON-FOOD PRODUCTS INTENDED FOR CONSUMERS CONCERNING DIHYDROXYINDOLINE HBR COLIPA n° : A147; OPINION_NUMBER=SCCNFP/0669/03; COMMITTEE=SCCNFP; REPORT_DATE=18 March 2003; VALUE_TEXT== 10; DOSE=Safety evaluation CALCULATION OF THE MARGIN OF SAFETY (Dihydroxyindoline HBr) (Air oxidative/semi-permanent) Based on a usage volume of 50 ml, containing at maximum 2 % Maximum absorption through the skin A (µg/cm2) = 1766 µg/cm2 Typical body weight of human = 60 kg Skin Area surface SAS (cm2) = 700 cm2 Dermal absorption per treatment SAS x A x...; EFFECT=19 2.11. Safety evaluation CALCULATION OF THE MARGIN OF SAFETY (Dihydroxyindoline HBr) (Air oxidative/semi-permanent) Based on a usage volume of 50 ml, containing at maximum 2 % Maximum absorption through the skin A (µg/cm2) = 1766 µg/cm2 Typical body weight of human = 60 kg Skin Area surface SAS (cm2) = 700 cm2 Dermal absorption per treatment SAS x A x 0.001 = 1236 µg Systemic exposure dose (SED) SAS x A x 0.001/60 = 0.021 mg/kg No observed effect level (mg/kg) NOEL = 10 mg/kg (rat, 90 day, oral) Margin of Safety NOEL / SED = 476 2.12. Conclusions Insufficient information is provided on potential impurities. The database on toxicological properties is poor. Acute toxicity, irritation, sensitisation and embryotoxicity have been adequately investigated, following appropriate guidelines and GLP where relevant. It was irritant to the rabbit eye, but not skin when tested neat, and it is unlikely that similar results would occur under realistic conditions of use. It has shown sensitising potential and formulations should be labelled; CITATION_NUMBERS=[]; DETAILS_JSON={"cas_number":"29539-03-5","citation":"","dose":"Safety evaluation CALCULATION OF THE MARGIN OF SAFETY (Dihydroxyindoline HBr) (Air oxidative/semi-permanent) Based on a usage volume of 50 ml, containing at maximum 2 % Maximum absorption through the skin A (µg/cm2) = 1766 µg/cm2 Typical body weight of human = 60 kg Skin Area surface SAS (cm2) = 700 cm2 Dermal absorption per treatment SAS x A x...","duration":"90 day","effect":"19 2.11. Safety evaluation CALCULATION OF THE MARGIN OF SAFETY (Dihydroxyindoline HBr) (Air oxidative/semi-permanent) Based on a usage volume of 50 ml, containing at maximum 2 % Maximum absorption through the skin A (µg/cm2) = 1766 µg/cm2 Typical body weight of human = 60 kg Skin Area surface SAS (cm2) = 700 cm2 Dermal absorption per treatment SAS x A x 0.001 = 1236 µg Systemic exposure dose (SED) SAS x A x 0.001/60 = 0.021 mg/kg No observed effect level (mg/kg) NOEL = 10 mg/kg (rat, 90 day, oral) Margin of Safety NOEL / SED = 476 2.12. Conclusions Insufficient information is provided on potential impurities. The database on toxicological properties is poor. Acute toxicity, irritation, sensitisation and embryotoxicity have been adequately investigated, following appropriate guidelines and GLP where relevant. It was irritant to the rabbit eye, but not skin when tested neat, and it is unlikely that similar results would occur under realistic conditions of use. It has shown sensitising potential and formulations should be labelled","endpoint":"dermal absorption","ingredient":"5,6-Dihydroxy indoline x HBr","loael_value":"","noael_unit":"mg/kg","noael_value":"= 10","page":18,"route":"oral","species":"rat","study_id":"out_193_noael_007"} |
| UnifiedCodex:SCCNFP:beta.noael_studies | repeated dose toxicity | 10 | mg/kg/day | rat | dermal | Sub-chronic | repeated dose toxicity | SOURCE_SUBDIR=out_193; REPORT_TITLE=OPINION OF THE SCIENTIFIC COMMITTEE ON COSMETIC PRODUCTS AND NON-FOOD PRODUCTS INTENDED FOR CONSUMERS CONCERNING DIHYDROXYINDOLINE HBR COLIPA n° : A147; OPINION_NUMBER=SCCNFP/0669/03; COMMITTEE=SCCNFP; REPORT_DATE=18 March 2003; VALUE_TEXT=10; DOSE=ysiological background of brownish pigmentation, treatment-related exogenous pigments were found in kidneys of animals receiving doses of at least 20 mg/kg/day, with only occasional pigments found at the lowest dose (10 mg/kg/day).; EFFECT=ysiological background of brownish pigmentation, treatment-related exogenous pigments were found in kidneys of animals receiving doses of at least 20 mg/kg/day, with only occasional pigments found at the lowest dose (10 mg/kg/day). There were neither functional nor histological findings indicative for intestinal or renal injury, whether in treated or untreated animals. Due to the fact that if even minor signs of exogenous pigments were found in kidneys of rats dosed with 20 mg/kg/day, the no-observed effect-level (NOEL) was established at 10 mg/kg/day. Ref. : 19 2.3.8. Sub-chronic dermal toxicity No data 2.3.9. Sub-chronic inhalation toxicity No data; CITATION=Ref. : 19 2; CITATION_NUMBERS=[19,2]; REFERENCE=Ref. : 19 2; DETAILS_JSON={"cas_number":"29539-03-5","citation":"Ref. : 19 2","dose":"ysiological background of brownish pigmentation, treatment-related exogenous pigments were found in kidneys of animals receiving doses of at least 20 mg/kg/day, with only occasional pigments found at the lowest dose (10 mg/kg/day).","duration":"Sub-chronic","effect":"ysiological background of brownish pigmentation, treatment-related exogenous pigments were found in kidneys of animals receiving doses of at least 20 mg/kg/day, with only occasional pigments found at the lowest dose (10 mg/kg/day). There were neither functional nor histological findings indicative for intestinal or renal injury, whether in treated or untreated animals. Due to the fact that if even minor signs of exogenous pigments were found in kidneys of rats dosed with 20 mg/kg/day, the no-observed effect-level (NOEL) was established at 10 mg/kg/day. Ref. : 19 2.3.8. Sub-chronic dermal toxicity No data 2.3.9. Sub-chronic inhalation toxicity No data","endpoint":"repeated dose toxicity","ingredient":"5,6-Dihydroxy indoline x HBr","loael_value":"","noael_unit":"mg/kg/day","noael_value":"10","page":9,"route":"dermal","species":"rat","study_id":"out_193_noael_004"} |
| UnifiedCodex:SCCNFP:beta.noael_studies | repeated dose toxicity | 10 | mg/kg bw/day | rat | oral | subchronic | repeated dose toxicity | SOURCE_SUBDIR=out_193; REPORT_TITLE=OPINION OF THE SCIENTIFIC COMMITTEE ON COSMETIC PRODUCTS AND NON-FOOD PRODUCTS INTENDED FOR CONSUMERS CONCERNING DIHYDROXYINDOLINE HBR COLIPA n° : A147; OPINION_NUMBER=SCCNFP/0669/03; COMMITTEE=SCCNFP; REPORT_DATE=18 March 2003; VALUE_TEXT=10; DOSE=Three subchronic oral dosing studies in rats indicate a NOEL of 10 mg/kg bw/day.; EFFECT=ies. The database on toxicological properties is poor. Acute toxicity, irritation, sensitisation and embryotoxicity have been adequately investigated, following appropriate guidelines and GLP where relevant. It was irritant to the rabbit eye, but not skin when tested neat, and it is unlikely that similar results would occur under realistic conditions of use. It has shown sensitising potential and formulations should be labelled with a warning in this respect. Three subchronic oral dosing studies in rats indicate a NOEL of 10 mg/kg bw/day. Skin penetration has been investigated in the rat in vivo. Sufficient information on tissue distribution and recovery is provided to assume that the results are acceptable. The percutaneous absorption study was performed with a 1.0 % formulation, where, in case of a semi-permanent hair dye, the foreseen use concentration is 2.0%. Comparing the NOEL with the maximum systemic exposure dose in humans indicates a safety margin of 476. A 147 was tested in bacterial cells for gene mutation in differe; CITATION_NUMBERS=[]; DETAILS_JSON={"cas_number":"29539-03-5","citation":"","dose":"Three subchronic oral dosing studies in rats indicate a NOEL of 10 mg/kg bw/day.","duration":"subchronic","effect":"ies. The database on toxicological properties is poor. Acute toxicity, irritation, sensitisation and embryotoxicity have been adequately investigated, following appropriate guidelines and GLP where relevant. It was irritant to the rabbit eye, but not skin when tested neat, and it is unlikely that similar results would occur under realistic conditions of use. It has shown sensitising potential and formulations should be labelled with a warning in this respect. Three subchronic oral dosing studies in rats indicate a NOEL of 10 mg/kg bw/day. Skin penetration has been investigated in the rat in vivo. Sufficient information on tissue distribution and recovery is provided to assume that the results are acceptable. The percutaneous absorption study was performed with a 1.0 % formulation, where, in case of a semi-permanent hair dye, the foreseen use concentration is 2.0%. Comparing the NOEL with the maximum systemic exposure dose in humans indicates a safety margin of 476. A 147 was tested in bacterial cells for gene mutation in differe","endpoint":"repeated dose toxicity","ingredient":"5,6-Dihydroxy indoline x HBr","loael_value":"","noael_unit":"mg/kg bw/day","noael_value":"10","page":18,"route":"oral","species":"rat","study_id":"out_193_noael_008"} |
| UnifiedCodex:SCCNFP:beta.noael_studies | repeated dose toxicity | 2 | % | rat | oral | subchronic | repeated dose toxicity | SOURCE_SUBDIR=out_193; REPORT_TITLE=OPINION OF THE SCIENTIFIC COMMITTEE ON COSMETIC PRODUCTS AND NON-FOOD PRODUCTS INTENDED FOR CONSUMERS CONCERNING DIHYDROXYINDOLINE HBR COLIPA n° : A147; OPINION_NUMBER=SCCNFP/0669/03; COMMITTEE=SCCNFP; REPORT_DATE=18 March 2003; VALUE_TEXT=2.0; DOSE=Three subchronic oral dosing studies in rats indicate a NOEL of 10 mg/kg bw/day.; EFFECT=wn sensitising potential and formulations should be labelled with a warning in this respect. Three subchronic oral dosing studies in rats indicate a NOEL of 10 mg/kg bw/day. Skin penetration has been investigated in the rat in vivo. Sufficient information on tissue distribution and recovery is provided to assume that the results are acceptable. The percutaneous absorption study was performed with a 1.0 % formulation, where, in case of a semi-permanent hair dye, the foreseen use concentration is 2.0%. Comparing the NOEL with the maximum systemic exposure dose in humans indicates a safety margin of 476. A 147 was tested in bacterial cells for gene mutation in different experiments and gave positive results. The in vitro test for mammalian gene mutation assay is negative. The in vitro test for clastogenicity in human lymphocytes was negative but the study is considered inadequate. The in vivo UDS on rats hepatocytes is negative. The in vivo micronucleus test in mice gave negative results. Dihydroxyindoline HBr may be considered not; CITATION_NUMBERS=[]; DETAILS_JSON={"cas_number":"29539-03-5","citation":"","dose":"Three subchronic oral dosing studies in rats indicate a NOEL of 10 mg/kg bw/day.","duration":"subchronic","effect":"wn sensitising potential and formulations should be labelled with a warning in this respect. Three subchronic oral dosing studies in rats indicate a NOEL of 10 mg/kg bw/day. Skin penetration has been investigated in the rat in vivo. Sufficient information on tissue distribution and recovery is provided to assume that the results are acceptable. The percutaneous absorption study was performed with a 1.0 % formulation, where, in case of a semi-permanent hair dye, the foreseen use concentration is 2.0%. Comparing the NOEL with the maximum systemic exposure dose in humans indicates a safety margin of 476. A 147 was tested in bacterial cells for gene mutation in different experiments and gave positive results. The in vitro test for mammalian gene mutation assay is negative. The in vitro test for clastogenicity in human lymphocytes was negative but the study is considered inadequate. The in vivo UDS on rats hepatocytes is negative. The in vivo micronucleus test in mice gave negative results. Dihydroxyindoline HBr may be considered not","endpoint":"repeated dose toxicity","ingredient":"5,6-Dihydroxy indoline x HBr","loael_value":"","noael_unit":"%","noael_value":"2.0","page":18,"route":"oral","species":"rat","study_id":"out_193_noael_009"} |
openFDA substances 4 endpoints
| Source | Endpoint Type | Value | Unit | Species | Route | Duration | Study Type | Reference |
|---|---|---|---|---|---|---|---|---|
| openFDA substances | FDA UNII substance identifier | HH49N58FJ9 | UNII | - | - | - | chemical | {"approval_status":null,"molecular_formula":"C8H9NO2","source_table":"substance_identifiers_fda","substance_class":"chemical","unii_code":"HH49N58FJ9"} |
| openFDA substances | FDA UNII substance identifier | HH49N58FJ9 | UNII | - | - | - | chemical | {"approval_status":null,"molecular_formula":"C8H9NO2","source_table":"substance_identifiers_fda","substance_class":"chemical","unii_code":"HH49N58FJ9"} |
| openFDA substances | FDA UNII substance identifier | HH49N58FJ9 | UNII | - | - | - | chemical | {"approval_status":null,"molecular_formula":"C8H9NO2","source_table":"substance_identifiers_fda","substance_class":"chemical","unii_code":"HH49N58FJ9"} |
| openFDA substances | FDA UNII substance identifier | HH49N58FJ9 | UNII | - | - | - | chemical | {"approval_status":null,"molecular_formula":"C8H9NO2","source_table":"substance_identifiers_fda","substance_class":"chemical","unii_code":"HH49N58FJ9"} |