NOAEL Studies
Cosmetic Ingredient
DIHYDROXYINDOLE NOAEL Studies
CAS: 3131-52-0
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 | 10 | mg/kg bw/day | rat | oral | 91 day | Subchronic | SCCP; L. Vallet. 13-Week Toxicity Study by Oral Route (Gavage) in Rats. CIT Study No. 7702TCR, 1992 |
| COSMOS_DB | NOAEL | 3 | mg/kg bw/day | rat | oral | 91 day | Subchronic | SCCP; L. Vallet. 13-Week Toxicity Study by Oral Route (Gavage) in Rats. CIT Study No. 7702TCR, 1992 |
SCCNFP_vision_codex 20 endpoints
| Source | Endpoint Type | Value | Unit | Species | Route | Duration | Study Type | Reference |
|---|---|---|---|---|---|---|---|---|
| SCCNFP_vision_codex | NOAEL | =10 | mg/kg bw/day | rat | dermal | Sub-chronic | repeated dose toxicity | {"citation":"Ref. : 5 2","dose":"Dihydroxyindole _____________________________________________________________________________________________ 8 On the basis of the increased triglyceride and accumulation of pigment in the kidney at 30 and 100 mg/kg bw/day, the study authors concluded that the dose level of 10 mg/kg bw/day was the NOAEL.","effect":"SCCNFP/0657/03, final Evaluation and opinion on : Dihydroxyindole _____________________________________________________________________________________________ 8 On the basis of the increased triglyceride and accumulation of pigment in the kidney at 30 and 100 mg/kg bw/day, the study authors concluded that the dose level of 10 mg/kg bw/day was the NOAEL. A significant change in urinalysis (ketones) was observed at 10 mg/kg bw/day, which could be related to the effects seen at higher doses, and therefore the NOEL is 3 mg/kg bw/day. Male rats appear to be more sensitive than females to the effects of this substance. Ref. : 5 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) Irritancy of 6% solution Guideline : OECD 404 Species/strain : Hyb","page":8,"pdf":"out_205_en.pdf","row_type":"noael_study","study_id":"out_205_en_noael_001"} |
| SCCNFP_vision_codex | NOAEL | =3 | mg/kg bw/day | rat | dermal | Sub-chronic | repeated dose toxicity | {"citation":"Ref. : 5 2","dose":"Dihydroxyindole _____________________________________________________________________________________________ 8 On the basis of the increased triglyceride and accumulation of pigment in the kidney at 30 and 100 mg/kg bw/day, the study authors concluded that the dose level of 10 mg/kg bw/day was the NOAEL.","effect":"SCCNFP/0657/03, final Evaluation and opinion on : Dihydroxyindole _____________________________________________________________________________________________ 8 On the basis of the increased triglyceride and accumulation of pigment in the kidney at 30 and 100 mg/kg bw/day, the study authors concluded that the dose level of 10 mg/kg bw/day was the NOAEL. A significant change in urinalysis (ketones) was observed at 10 mg/kg bw/day, which could be related to the effects seen at higher doses, and therefore the NOEL is 3 mg/kg bw/day. Male rats appear to be more sensitive than females to the effects of this substance. Ref. : 5 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) Irritancy of 6% solution Guideline : OECD 404 Species/strain : Hybrid New Zealand albino rabbit Group size : 6 male Test substance : 5,6-hydroxyindole: 6% in glycerol Batch no : Batch op1E (purity not stated in study report) Dos","page":8,"pdf":"out_205_en.pdf","row_type":"noael_study","study_id":"out_205_en_noael_002"} |
| SCCNFP_vision_codex | NOAEL | =100 | mg/kg bw/day | rat | - | - | developmental toxicity | {"citation":"Ref. : 13 2","dose":"_____________________________ 12 The mean numbers of corpora lutea, implantation sites, post-implantation loss, live foetuses and foetal bodyweights were similar for control and treated groups.","effect":"_____________________________ 12 The mean numbers of corpora lutea, implantation sites, post-implantation loss, live foetuses and foetal bodyweights were similar for control and treated groups. No treatment-related foetal anomalies or malformations were observed. The authors concluded that the test substance was well tolerated by the pregnant female rat at dose levels of 20 and 100 mg/kg bw/day. The dose of 250 mg/kg bw/day was considered to be toxic for the pregnant female but not embryo-toxic or teratogenic. The NOAEL was defined as 100 mg/kg bw/day for materno-toxicity and 250 mg/kg bw/day for embryo-foetal development. Ref. : 13 2.7. Toxicokinetics (incl. Percutaneous Absorption) Percutaneous Absorption in vitro Guideline : / Tissue : Human female abdominal skin, dermatomed Method : Franz diffusion cell (static) Test substance : P39, 4.6% in “GEL PROGRESS” formulation, batch number 48.791 Batch no : OP33 (radiochemical purity 93.4%) Dose levels : 1003.9 \u0004g/cm2 in the presence of 10.58 mg hair 805.8 \u0004g/cm2 in the absence of ha","page":12,"pdf":"out_205_en.pdf","row_type":"noael_study","study_id":"out_205_en_noael_003"} |
| SCCNFP_vision_codex | NOAEL | =3 | mg/kg | rat | oral | 13 weeks | dermal absorption | {"dose":"Safety evaluation CALCULATION OF THE MARGIN OF SAFETY (Dihydroxyindole) (air oxidative) Based on a usage volume of 25 ml, containing at maximum 5 % Maximum absorption through the skin A (µg/cm²) = 25.65 \u0001g/cm² Typical body weight of human = 60 kg Skin Area Surface (scalp) SAS = 700 cm² Dermal absorption per treatment SAS x A x 0.001 = 17.96 mg S...","effect":"tive for the safety evaluation of COLIPA A111 in hair dye formulations. 2.11. Safety evaluation CALCULATION OF THE MARGIN OF SAFETY (Dihydroxyindole) (air oxidative) Based on a usage volume of 25 ml, containing at maximum 5 % Maximum absorption through the skin A (µg/cm²) = 25.65 \u0001g/cm² Typical body weight of human = 60 kg Skin Area Surface (scalp) SAS = 700 cm² Dermal absorption per treatment SAS x A x 0.001 = 17.96 mg Systemic exposure dose (SED) SAS x A x 0.001/ 60 = 0.299 mg/kg No observed effect level (mg/kg) NOEL = 3 mg/kg (rat, 13 weeks gavage) Margin of Safety NOEL / SED = 10","page":16,"pdf":"out_205_en.pdf","row_type":"noael_study","study_id":"out_205_en_noael_004"} |
| SCCNFP_vision_codex | NOAEL | =3 | mg/kg/day | rat | - | 13-week | NOAEL study | {"citation":"Ref: 93/02/03 (Feb 1993) 3","dose":"The NOEL from a rat 13-week study was 3 mg/kg/day.","effect":"ncer Research 42: 3783-3788 (Sept 1982). 12. Miranda, M., Bonfigli, A., Zarivi, O., Manilla, A., Cimini, A.M. and Arcadi, A., Mutagenesis 2: 45-50 (1987). 13. CIT, France. Report No. 12503 RSR (July 1995). 14. L’Oreal, France. Ref: 93/02/03 (Feb 1993) 3. Opinion of the SCCNFP Dihydroxyindole is clastogenic in vitro with and without metabolic activation but is not a bacterial mutagen. One in vivo study (in vivo/in vitro rat hepatocytes) indicates that the compound is not an in vivo somatic cell genotoxic agent. The NOEL from a rat 13-week study was 3 mg/kg/day. In vitro studies indicate a maximum value of 25.65 \u0004g/cm2 for percutaneous penetration considering the epidermis, dermis and receptor fluid compartments. Comparing the NOEL with the maximum systemic exposure dose in humans indicated a margin of safety of 10, which is not adequate. The SCCNFP is of the opinion that Dihydroxyindole is not suitable for use in hair dyes. 4. Other considerations / 5. Minority opinions /","page":18,"pdf":"out_205_en.pdf","row_type":"noael_study","study_id":"out_205_en_noael_010"} |
| SCCNFP_vision_codex | NOAEL | =10 | mg/kg bw/day | rat | dermal | Sub-chronic | repeated dose toxicity | {"citation":"Ref. : 5 2","dose":"Dihydroxyindole _____________________________________________________________________________________________ 8 On the basis of the increased triglyceride and accumulation of pigment in the kidney at 30 and 100 mg/kg bw/day, the study authors concluded that the dose level of 10 mg/kg bw/day was the NOAEL.","effect":"SCCNFP/0657/03, final Evaluation and opinion on : Dihydroxyindole _____________________________________________________________________________________________ 8 On the basis of the increased triglyceride and accumulation of pigment in the kidney at 30 and 100 mg/kg bw/day, the study authors concluded that the dose level of 10 mg/kg bw/day was the NOAEL. A significant change in urinalysis (ketones) was observed at 10 mg/kg bw/day, which could be related to the effects seen at higher doses, and therefore the NOEL is 3 mg/kg bw/day. Male rats appear to be more sensitive than females to the effects of this substance. Ref. : 5 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) Irritancy of 6% solution Guideline : OECD 404 Species/strain : Hyb","page":8,"pdf":"out_205_en.pdf","row_type":"noael_study","study_id":"out_205_en_noael_001"} |
| SCCNFP_vision_codex | NOAEL | =3 | mg/kg bw/day | rat | dermal | Sub-chronic | repeated dose toxicity | {"citation":"Ref. : 5 2","dose":"Dihydroxyindole _____________________________________________________________________________________________ 8 On the basis of the increased triglyceride and accumulation of pigment in the kidney at 30 and 100 mg/kg bw/day, the study authors concluded that the dose level of 10 mg/kg bw/day was the NOAEL.","effect":"SCCNFP/0657/03, final Evaluation and opinion on : Dihydroxyindole _____________________________________________________________________________________________ 8 On the basis of the increased triglyceride and accumulation of pigment in the kidney at 30 and 100 mg/kg bw/day, the study authors concluded that the dose level of 10 mg/kg bw/day was the NOAEL. A significant change in urinalysis (ketones) was observed at 10 mg/kg bw/day, which could be related to the effects seen at higher doses, and therefore the NOEL is 3 mg/kg bw/day. Male rats appear to be more sensitive than females to the effects of this substance. Ref. : 5 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) Irritancy of 6% solution Guideline : OECD 404 Species/strain : Hybrid New Zealand albino rabbit Group size : 6 male Test substance : 5,6-hydroxyindole: 6% in glycerol Batch no : Batch op1E (purity not stated in study report) Dos","page":8,"pdf":"out_205_en.pdf","row_type":"noael_study","study_id":"out_205_en_noael_002"} |
| SCCNFP_vision_codex | NOAEL | =100 | mg/kg bw/day | rat | - | - | developmental toxicity | {"citation":"Ref. : 13 2","dose":"_____________________________ 12 The mean numbers of corpora lutea, implantation sites, post-implantation loss, live foetuses and foetal bodyweights were similar for control and treated groups.","effect":"_____________________________ 12 The mean numbers of corpora lutea, implantation sites, post-implantation loss, live foetuses and foetal bodyweights were similar for control and treated groups. No treatment-related foetal anomalies or malformations were observed. The authors concluded that the test substance was well tolerated by the pregnant female rat at dose levels of 20 and 100 mg/kg bw/day. The dose of 250 mg/kg bw/day was considered to be toxic for the pregnant female but not embryo-toxic or teratogenic. The NOAEL was defined as 100 mg/kg bw/day for materno-toxicity and 250 mg/kg bw/day for embryo-foetal development. Ref. : 13 2.7. Toxicokinetics (incl. Percutaneous Absorption) Percutaneous Absorption in vitro Guideline : / Tissue : Human female abdominal skin, dermatomed Method : Franz diffusion cell (static) Test substance : P39, 4.6% in “GEL PROGRESS” formulation, batch number 48.791 Batch no : OP33 (radiochemical purity 93.4%) Dose levels : 1003.9 \u0004g/cm2 in the presence of 10.58 mg hair 805.8 \u0004g/cm2 in the absence of ha","page":12,"pdf":"out_205_en.pdf","row_type":"noael_study","study_id":"out_205_en_noael_003"} |
| SCCNFP_vision_codex | NOAEL | =3 | mg/kg | rat | oral | 13 weeks | dermal absorption | {"dose":"Safety evaluation CALCULATION OF THE MARGIN OF SAFETY (Dihydroxyindole) (air oxidative) Based on a usage volume of 25 ml, containing at maximum 5 % Maximum absorption through the skin A (µg/cm²) = 25.65 \u0001g/cm² Typical body weight of human = 60 kg Skin Area Surface (scalp) SAS = 700 cm² Dermal absorption per treatment SAS x A x 0.001 = 17.96 mg S...","effect":"tive for the safety evaluation of COLIPA A111 in hair dye formulations. 2.11. Safety evaluation CALCULATION OF THE MARGIN OF SAFETY (Dihydroxyindole) (air oxidative) Based on a usage volume of 25 ml, containing at maximum 5 % Maximum absorption through the skin A (µg/cm²) = 25.65 \u0001g/cm² Typical body weight of human = 60 kg Skin Area Surface (scalp) SAS = 700 cm² Dermal absorption per treatment SAS x A x 0.001 = 17.96 mg Systemic exposure dose (SED) SAS x A x 0.001/ 60 = 0.299 mg/kg No observed effect level (mg/kg) NOEL = 3 mg/kg (rat, 13 weeks gavage) Margin of Safety NOEL / SED = 10","page":16,"pdf":"out_205_en.pdf","row_type":"noael_study","study_id":"out_205_en_noael_004"} |
| SCCNFP_vision_codex | NOAEL | =3 | mg/kg/day | rat | - | 13-week | NOAEL study | {"citation":"Ref: 93/02/03 (Feb 1993) 3","dose":"The NOEL from a rat 13-week study was 3 mg/kg/day.","effect":"ncer Research 42: 3783-3788 (Sept 1982). 12. Miranda, M., Bonfigli, A., Zarivi, O., Manilla, A., Cimini, A.M. and Arcadi, A., Mutagenesis 2: 45-50 (1987). 13. CIT, France. Report No. 12503 RSR (July 1995). 14. L’Oreal, France. Ref: 93/02/03 (Feb 1993) 3. Opinion of the SCCNFP Dihydroxyindole is clastogenic in vitro with and without metabolic activation but is not a bacterial mutagen. One in vivo study (in vivo/in vitro rat hepatocytes) indicates that the compound is not an in vivo somatic cell genotoxic agent. The NOEL from a rat 13-week study was 3 mg/kg/day. In vitro studies indicate a maximum value of 25.65 \u0004g/cm2 for percutaneous penetration considering the epidermis, dermis and receptor fluid compartments. Comparing the NOEL with the maximum systemic exposure dose in humans indicated a margin of safety of 10, which is not adequate. The SCCNFP is of the opinion that Dihydroxyindole is not suitable for use in hair dyes. 4. Other considerations / 5. Minority opinions /","page":18,"pdf":"out_205_en.pdf","row_type":"noael_study","study_id":"out_205_en_noael_010"} |
| SCCNFP_vision_codex | NOAEL | =10 | mg/kg bw/day | rat | dermal | Sub-chronic | repeated dose toxicity | {"citation":"Ref. : 5 2","dose":"Dihydroxyindole _____________________________________________________________________________________________ 8 On the basis of the increased triglyceride and accumulation of pigment in the kidney at 30 and 100 mg/kg bw/day, the study authors concluded that the dose level of 10 mg/kg bw/day was the NOAEL.","effect":"SCCNFP/0657/03, final Evaluation and opinion on : Dihydroxyindole _____________________________________________________________________________________________ 8 On the basis of the increased triglyceride and accumulation of pigment in the kidney at 30 and 100 mg/kg bw/day, the study authors concluded that the dose level of 10 mg/kg bw/day was the NOAEL. A significant change in urinalysis (ketones) was observed at 10 mg/kg bw/day, which could be related to the effects seen at higher doses, and therefore the NOEL is 3 mg/kg bw/day. Male rats appear to be more sensitive than females to the effects of this substance. Ref. : 5 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) Irritancy of 6% solution Guideline : OECD 404 Species/strain : Hyb","page":8,"pdf":"out_205_en.pdf","row_type":"noael_study","study_id":"out_205_en_noael_001"} |
| SCCNFP_vision_codex | NOAEL | =3 | mg/kg bw/day | rat | dermal | Sub-chronic | repeated dose toxicity | {"citation":"Ref. : 5 2","dose":"Dihydroxyindole _____________________________________________________________________________________________ 8 On the basis of the increased triglyceride and accumulation of pigment in the kidney at 30 and 100 mg/kg bw/day, the study authors concluded that the dose level of 10 mg/kg bw/day was the NOAEL.","effect":"SCCNFP/0657/03, final Evaluation and opinion on : Dihydroxyindole _____________________________________________________________________________________________ 8 On the basis of the increased triglyceride and accumulation of pigment in the kidney at 30 and 100 mg/kg bw/day, the study authors concluded that the dose level of 10 mg/kg bw/day was the NOAEL. A significant change in urinalysis (ketones) was observed at 10 mg/kg bw/day, which could be related to the effects seen at higher doses, and therefore the NOEL is 3 mg/kg bw/day. Male rats appear to be more sensitive than females to the effects of this substance. Ref. : 5 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) Irritancy of 6% solution Guideline : OECD 404 Species/strain : Hybrid New Zealand albino rabbit Group size : 6 male Test substance : 5,6-hydroxyindole: 6% in glycerol Batch no : Batch op1E (purity not stated in study report) Dos","page":8,"pdf":"out_205_en.pdf","row_type":"noael_study","study_id":"out_205_en_noael_002"} |
| SCCNFP_vision_codex | NOAEL | =100 | mg/kg bw/day | rat | - | - | developmental toxicity | {"citation":"Ref. : 13 2","dose":"_____________________________ 12 The mean numbers of corpora lutea, implantation sites, post-implantation loss, live foetuses and foetal bodyweights were similar for control and treated groups.","effect":"_____________________________ 12 The mean numbers of corpora lutea, implantation sites, post-implantation loss, live foetuses and foetal bodyweights were similar for control and treated groups. No treatment-related foetal anomalies or malformations were observed. The authors concluded that the test substance was well tolerated by the pregnant female rat at dose levels of 20 and 100 mg/kg bw/day. The dose of 250 mg/kg bw/day was considered to be toxic for the pregnant female but not embryo-toxic or teratogenic. The NOAEL was defined as 100 mg/kg bw/day for materno-toxicity and 250 mg/kg bw/day for embryo-foetal development. Ref. : 13 2.7. Toxicokinetics (incl. Percutaneous Absorption) Percutaneous Absorption in vitro Guideline : / Tissue : Human female abdominal skin, dermatomed Method : Franz diffusion cell (static) Test substance : P39, 4.6% in “GEL PROGRESS” formulation, batch number 48.791 Batch no : OP33 (radiochemical purity 93.4%) Dose levels : 1003.9 \u0004g/cm2 in the presence of 10.58 mg hair 805.8 \u0004g/cm2 in the absence of ha","page":12,"pdf":"out_205_en.pdf","row_type":"noael_study","study_id":"out_205_en_noael_003"} |
| SCCNFP_vision_codex | NOAEL | =3 | mg/kg | rat | oral | 13 weeks | dermal absorption | {"dose":"Safety evaluation CALCULATION OF THE MARGIN OF SAFETY (Dihydroxyindole) (air oxidative) Based on a usage volume of 25 ml, containing at maximum 5 % Maximum absorption through the skin A (µg/cm²) = 25.65 \u0001g/cm² Typical body weight of human = 60 kg Skin Area Surface (scalp) SAS = 700 cm² Dermal absorption per treatment SAS x A x 0.001 = 17.96 mg S...","effect":"tive for the safety evaluation of COLIPA A111 in hair dye formulations. 2.11. Safety evaluation CALCULATION OF THE MARGIN OF SAFETY (Dihydroxyindole) (air oxidative) Based on a usage volume of 25 ml, containing at maximum 5 % Maximum absorption through the skin A (µg/cm²) = 25.65 \u0001g/cm² Typical body weight of human = 60 kg Skin Area Surface (scalp) SAS = 700 cm² Dermal absorption per treatment SAS x A x 0.001 = 17.96 mg Systemic exposure dose (SED) SAS x A x 0.001/ 60 = 0.299 mg/kg No observed effect level (mg/kg) NOEL = 3 mg/kg (rat, 13 weeks gavage) Margin of Safety NOEL / SED = 10","page":16,"pdf":"out_205_en.pdf","row_type":"noael_study","study_id":"out_205_en_noael_004"} |
| SCCNFP_vision_codex | NOAEL | =3 | mg/kg/day | rat | - | 13-week | NOAEL study | {"citation":"Ref: 93/02/03 (Feb 1993) 3","dose":"The NOEL from a rat 13-week study was 3 mg/kg/day.","effect":"ncer Research 42: 3783-3788 (Sept 1982). 12. Miranda, M., Bonfigli, A., Zarivi, O., Manilla, A., Cimini, A.M. and Arcadi, A., Mutagenesis 2: 45-50 (1987). 13. CIT, France. Report No. 12503 RSR (July 1995). 14. L’Oreal, France. Ref: 93/02/03 (Feb 1993) 3. Opinion of the SCCNFP Dihydroxyindole is clastogenic in vitro with and without metabolic activation but is not a bacterial mutagen. One in vivo study (in vivo/in vitro rat hepatocytes) indicates that the compound is not an in vivo somatic cell genotoxic agent. The NOEL from a rat 13-week study was 3 mg/kg/day. In vitro studies indicate a maximum value of 25.65 \u0004g/cm2 for percutaneous penetration considering the epidermis, dermis and receptor fluid compartments. Comparing the NOEL with the maximum systemic exposure dose in humans indicated a margin of safety of 10, which is not adequate. The SCCNFP is of the opinion that Dihydroxyindole is not suitable for use in hair dyes. 4. Other considerations / 5. Minority opinions /","page":18,"pdf":"out_205_en.pdf","row_type":"noael_study","study_id":"out_205_en_noael_010"} |
| SCCNFP_vision_codex | NOAEL | =10 | mg/kg bw/day | rat | dermal | Sub-chronic | repeated dose toxicity | {"citation":"Ref. : 5 2","dose":"Dihydroxyindole _____________________________________________________________________________________________ 8 On the basis of the increased triglyceride and accumulation of pigment in the kidney at 30 and 100 mg/kg bw/day, the study authors concluded that the dose level of 10 mg/kg bw/day was the NOAEL.","effect":"SCCNFP/0657/03, final Evaluation and opinion on : Dihydroxyindole _____________________________________________________________________________________________ 8 On the basis of the increased triglyceride and accumulation of pigment in the kidney at 30 and 100 mg/kg bw/day, the study authors concluded that the dose level of 10 mg/kg bw/day was the NOAEL. A significant change in urinalysis (ketones) was observed at 10 mg/kg bw/day, which could be related to the effects seen at higher doses, and therefore the NOEL is 3 mg/kg bw/day. Male rats appear to be more sensitive than females to the effects of this substance. Ref. : 5 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) Irritancy of 6% solution Guideline : OECD 404 Species/strain : Hyb","page":8,"pdf":"out_205_en.pdf","row_type":"noael_study","study_id":"out_205_en_noael_001"} |
| SCCNFP_vision_codex | NOAEL | =3 | mg/kg bw/day | rat | dermal | Sub-chronic | repeated dose toxicity | {"citation":"Ref. : 5 2","dose":"Dihydroxyindole _____________________________________________________________________________________________ 8 On the basis of the increased triglyceride and accumulation of pigment in the kidney at 30 and 100 mg/kg bw/day, the study authors concluded that the dose level of 10 mg/kg bw/day was the NOAEL.","effect":"SCCNFP/0657/03, final Evaluation and opinion on : Dihydroxyindole _____________________________________________________________________________________________ 8 On the basis of the increased triglyceride and accumulation of pigment in the kidney at 30 and 100 mg/kg bw/day, the study authors concluded that the dose level of 10 mg/kg bw/day was the NOAEL. A significant change in urinalysis (ketones) was observed at 10 mg/kg bw/day, which could be related to the effects seen at higher doses, and therefore the NOEL is 3 mg/kg bw/day. Male rats appear to be more sensitive than females to the effects of this substance. Ref. : 5 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) Irritancy of 6% solution Guideline : OECD 404 Species/strain : Hybrid New Zealand albino rabbit Group size : 6 male Test substance : 5,6-hydroxyindole: 6% in glycerol Batch no : Batch op1E (purity not stated in study report) Dos","page":8,"pdf":"out_205_en.pdf","row_type":"noael_study","study_id":"out_205_en_noael_002"} |
| SCCNFP_vision_codex | NOAEL | =100 | mg/kg bw/day | rat | - | - | developmental toxicity | {"citation":"Ref. : 13 2","dose":"_____________________________ 12 The mean numbers of corpora lutea, implantation sites, post-implantation loss, live foetuses and foetal bodyweights were similar for control and treated groups.","effect":"_____________________________ 12 The mean numbers of corpora lutea, implantation sites, post-implantation loss, live foetuses and foetal bodyweights were similar for control and treated groups. No treatment-related foetal anomalies or malformations were observed. The authors concluded that the test substance was well tolerated by the pregnant female rat at dose levels of 20 and 100 mg/kg bw/day. The dose of 250 mg/kg bw/day was considered to be toxic for the pregnant female but not embryo-toxic or teratogenic. The NOAEL was defined as 100 mg/kg bw/day for materno-toxicity and 250 mg/kg bw/day for embryo-foetal development. Ref. : 13 2.7. Toxicokinetics (incl. Percutaneous Absorption) Percutaneous Absorption in vitro Guideline : / Tissue : Human female abdominal skin, dermatomed Method : Franz diffusion cell (static) Test substance : P39, 4.6% in “GEL PROGRESS” formulation, batch number 48.791 Batch no : OP33 (radiochemical purity 93.4%) Dose levels : 1003.9 \u0004g/cm2 in the presence of 10.58 mg hair 805.8 \u0004g/cm2 in the absence of ha","page":12,"pdf":"out_205_en.pdf","row_type":"noael_study","study_id":"out_205_en_noael_003"} |
| SCCNFP_vision_codex | NOAEL | =3 | mg/kg | rat | oral | 13 weeks | dermal absorption | {"dose":"Safety evaluation CALCULATION OF THE MARGIN OF SAFETY (Dihydroxyindole) (air oxidative) Based on a usage volume of 25 ml, containing at maximum 5 % Maximum absorption through the skin A (µg/cm²) = 25.65 \u0001g/cm² Typical body weight of human = 60 kg Skin Area Surface (scalp) SAS = 700 cm² Dermal absorption per treatment SAS x A x 0.001 = 17.96 mg S...","effect":"tive for the safety evaluation of COLIPA A111 in hair dye formulations. 2.11. Safety evaluation CALCULATION OF THE MARGIN OF SAFETY (Dihydroxyindole) (air oxidative) Based on a usage volume of 25 ml, containing at maximum 5 % Maximum absorption through the skin A (µg/cm²) = 25.65 \u0001g/cm² Typical body weight of human = 60 kg Skin Area Surface (scalp) SAS = 700 cm² Dermal absorption per treatment SAS x A x 0.001 = 17.96 mg Systemic exposure dose (SED) SAS x A x 0.001/ 60 = 0.299 mg/kg No observed effect level (mg/kg) NOEL = 3 mg/kg (rat, 13 weeks gavage) Margin of Safety NOEL / SED = 10","page":16,"pdf":"out_205_en.pdf","row_type":"noael_study","study_id":"out_205_en_noael_004"} |
| SCCNFP_vision_codex | NOAEL | =3 | mg/kg/day | rat | - | 13-week | NOAEL study | {"citation":"Ref: 93/02/03 (Feb 1993) 3","dose":"The NOEL from a rat 13-week study was 3 mg/kg/day.","effect":"ncer Research 42: 3783-3788 (Sept 1982). 12. Miranda, M., Bonfigli, A., Zarivi, O., Manilla, A., Cimini, A.M. and Arcadi, A., Mutagenesis 2: 45-50 (1987). 13. CIT, France. Report No. 12503 RSR (July 1995). 14. L’Oreal, France. Ref: 93/02/03 (Feb 1993) 3. Opinion of the SCCNFP Dihydroxyindole is clastogenic in vitro with and without metabolic activation but is not a bacterial mutagen. One in vivo study (in vivo/in vitro rat hepatocytes) indicates that the compound is not an in vivo somatic cell genotoxic agent. The NOEL from a rat 13-week study was 3 mg/kg/day. In vitro studies indicate a maximum value of 25.65 \u0004g/cm2 for percutaneous penetration considering the epidermis, dermis and receptor fluid compartments. Comparing the NOEL with the maximum systemic exposure dose in humans indicated a margin of safety of 10, which is not adequate. The SCCNFP is of the opinion that Dihydroxyindole is not suitable for use in hair dyes. 4. Other considerations / 5. Minority opinions /","page":18,"pdf":"out_205_en.pdf","row_type":"noael_study","study_id":"out_205_en_noael_010"} |
SCCS_vision_codex 32 endpoints
| Source | Endpoint Type | Value | Unit | Species | Route | Duration | Study Type | Reference |
|---|---|---|---|---|---|---|---|---|
| SCCS_vision_codex | NOAEL | =10 | mg/kg bw/day | rat | - | - | NOAEL study | {"citation":"Ref.: 10 In the complementary dossier from 2004 the analytical interference between dihydroxyindole and/or its degradation products and the determination of urinary ketones using N-Multi","dose":"These changes occurred in some animals of both sex in the 30 and 100 mg/kg bw/day dose groups, and persisted at the end of the recovery period.","effect":"noted at autopsy, consistent with the microscopic observation of intracellular pigment accumulation in the cortical tubular epithelium. These changes occurred in some animals of both sex in the 30 and 100 mg/kg bw/day dose groups, and persisted at the end of the recovery period. No other histological abnormalities were reported. On the basis of the increased triglyceride and accumulation of pigment in the kidney at 30 and 100 mg/kg bw/day, the study authors concluded that the dose level of 10 mg/kg bw/day was the NOAEL. A significant change in urinalysis (ketones) was observed at 10 mg/kg bw/day, which could be related to the effects seen at higher doses, and therefore the NOEL is 3 mg/kg bw/day. Male rats appear to be more sensitive than females to the effects of this substance. Ref.: 10 In the complementary dossier from 2004 the analytical interference between dihydroxyindole and/or its degradation products and the determination of urinary ketones using N-Multistix SG test strips was investigated. From the results it can be c","page":14,"pdf":"sccp_o_045.pdf","row_type":"noael_study","study_id":"sccp_o_045_noael_001"} |
| SCCS_vision_codex | NOAEL | =3 | mg/kg bw/day | rat | - | - | NOAEL study | {"citation":"Ref.: 10 In the complementary dossier from 2004 the analytical interference between dihydroxyindole and/or its degradation products and the determination of urinary ketones using N-Multi","dose":"some animals of both sex in the 30 and 100 mg/kg bw/day dose groups, and persisted at the end of the recovery period.","effect":"some animals of both sex in the 30 and 100 mg/kg bw/day dose groups, and persisted at the end of the recovery period. No other histological abnormalities were reported. On the basis of the increased triglyceride and accumulation of pigment in the kidney at 30 and 100 mg/kg bw/day, the study authors concluded that the dose level of 10 mg/kg bw/day was the NOAEL. A significant change in urinalysis (ketones) was observed at 10 mg/kg bw/day, which could be related to the effects seen at higher doses, and therefore the NOEL is 3 mg/kg bw/day. Male rats appear to be more sensitive than females to the effects of this substance. Ref.: 10 In the complementary dossier from 2004 the analytical interference between dihydroxyindole and/or its degradation products and the determination of urinary ketones using N-Multistix SG test strips was investigated. From the results it can be concluded that false positive reactions for","page":14,"pdf":"sccp_o_045.pdf","row_type":"noael_study","study_id":"sccp_o_045_noael_002"} |
| SCCS_vision_codex | NOAEL | =1.5 | mg/kg bw/d | - | - | Chronic | NOAEL study | {"citation":"Ref.: 11 3","dose":"and bilirubin (high dose group).","effect":"and bilirubin (high dose group). Increases in the relative weights of spleen, kidney and liver accompanied by pigmentation were seen at the high dose and for the spleen also at 5 mg/kg bw/d (males). Substance-treated animals showed inflammation in the subcutaneous tissues and pigmentation in lymph nodes (pigmentary lymphadenopathy), spleen, liver thyroids. Kidney, adrenal cortex and ovaries, pigmentation was present even in the lowest dose group. In the recovery group the effects were maintained in some cases. No NOEL can be derived. The NOAEL was set by SCCP at 1.5 mg/kg bw/d. Ref.: 11 3.3.5.3. Chronic (> 12 months) toxicity","page":15,"pdf":"sccp_o_045.pdf","row_type":"noael_study","study_id":"sccp_o_045_noael_004"} |
| SCCS_vision_codex | NOAEL | =100 | mg/kg bw/day | rat | - | developmental | reproductive toxicity | {"citation":"Ref.: 17 3","dose":"The mean numbers of corpora lutea, implantation sites, post-implantation loss, live foetuses and foetal bodyweights were similar for control and treated groups.","effect":"macroscopic changes noted above. The mean numbers of corpora lutea, implantation sites, post-implantation loss, live foetuses and foetal bodyweights were similar for control and treated groups. No treatment-related foetal anomalies or malformations were observed. The authors concluded that the test substance was well tolerated by the pregnant female rat at dose levels of 20 and 100 mg/kg bw/day. The dose of 250 mg/kg bw/day was considered to be toxic for the pregnant female but not embryo-toxic or teratogenic. The NOAEL was defined as 100 mg/kg bw/day for maternal toxicity and 250 mg/kg bw/day for embryo-foetal development. Ref.: 17 3.3.8.3 Combined fertility, embryo-foetal and postnatal developmental toxicity Combined fertility, embryo-foetal and postnatal developmental toxicity by subcutaneous route in rats Guideline: / Species/strain: Sprague-Dawley rat, Crl CD (SD) BR strain Group size: 10 males + 10 females Test substance: dihydroxyindole (P39) in saline Batch: Op.3X Purity: 99 % Dose: 0, 5, and 15 mg/kg bw/day Treatment:","page":20,"pdf":"sccp_o_045.pdf","row_type":"noael_study","study_id":"sccp_o_045_noael_006"} |
| SCCS_vision_codex | NOAEL | =15 | mg/kg bw/d | rat | dermal | - | reproductive toxicity | {"citation":"Ref.: 18 3","dose":"Body weight gain and food consumption was decreased in the 15 mg/kg group.","effect":"hts were measured regularly. Pregnant females were allowed to deliver their litters (F1) which were monitored for survival and growth. F0 males and females and F1 pups were sacrificed between day 8 and 10 post partum. Local signs were observed at the injection sites (erythema, scabs, discolouration, nodules, oedema, and thickening). Body weight gain and food consumption was decreased in the 15 mg/kg group. Reproductive performance of the parent as well as survival and growth of the offspring was not affected. The NOAEL was set at 15 mg/kg bw/d. Ref.: 18 3.3.9. Toxicokinetics Toxicokinetic study after single cutaneous application to rats Guideline: / Species/strain: Sprague-Dawley rat Group size: 12 males + 12 females Test substance: [14C] dihydroxyindole (P39) in PEG 300 Batch: 92170 ([14C]-labelled) and Op.3X Dose: 25 mg/kg bw (18.5 MBq/kg), single dermal application Sampling time: 1.8, 2.24, 4.48, 96, 144 and 216 h GLP: in compliance Test batches Op.3X (unlabelled dihydroxyindole, 99% pure) and 92170 (radiolabelled dihydro","page":21,"pdf":"sccp_o_045.pdf","row_type":"noael_study","study_id":"sccp_o_045_noael_007"} |
| SCCS_vision_codex | NOAEL | =0.012 | mg/kg | rat | dermal | 13-week | dermal absorption | {"citation":"Ref.: 23 3","dose":"Safety evaluation (including calculation of the MoS) CALCULATION OF THE MARGIN OF SAFETY Maximum absorption through the skin A (µg/cm2) = 1.0 µg/cm2 Skin Area surface SAS (cm2) = 700 cm2 Dermal absorption per treatment SAS x A x 0.001 = 0.7 mg Typical body weight of human = 60 kg Systemic exposure dose (SED) SAS x A x 0.001/60 = 0.012 mg/kg No o...","effect":"/ml and in water at and above 100 µg/l. It can be concluded that false positive reactions for ketone bodies were induced in the presence of hydroxyindole. Ref.: 23 3.3.13. Safety evaluation (including calculation of the MoS) CALCULATION OF THE MARGIN OF SAFETY Maximum absorption through the skin A (µg/cm2) = 1.0 µg/cm2 Skin Area surface SAS (cm2) = 700 cm2 Dermal absorption per treatment SAS x A x 0.001 = 0.7 mg Typical body weight of human = 60 kg Systemic exposure dose (SED) SAS x A x 0.001/60 = 0.012 mg/kg No observed adverse effect level (mg/kg) NOAEL = 1.5 mg/kg (rat, 13-week, subcutaneous) Margin of Safety NOAEL / SED = 125","page":23,"pdf":"sccp_o_045.pdf","row_type":"noael_study","study_id":"sccp_o_045_noael_008"} |
| SCCS_vision_codex | NOAEL | =1.5 | mg/kg | rat | dermal | 13-week | dermal absorption | {"citation":"Ref.: 23 3","dose":"Safety evaluation (including calculation of the MoS) CALCULATION OF THE MARGIN OF SAFETY Maximum absorption through the skin A (µg/cm2) = 1.0 µg/cm2 Skin Area surface SAS (cm2) = 700 cm2 Dermal absorption per treatment SAS x A x 0.001 = 0.7 mg Typical body weight of human = 60 kg Systemic exposure dose (SED) SAS x A x 0.001/60 = 0.012 mg/kg No o...","effect":"t can be concluded that false positive reactions for ketone bodies were induced in the presence of hydroxyindole. Ref.: 23 3.3.13. Safety evaluation (including calculation of the MoS) CALCULATION OF THE MARGIN OF SAFETY Maximum absorption through the skin A (µg/cm2) = 1.0 µg/cm2 Skin Area surface SAS (cm2) = 700 cm2 Dermal absorption per treatment SAS x A x 0.001 = 0.7 mg Typical body weight of human = 60 kg Systemic exposure dose (SED) SAS x A x 0.001/60 = 0.012 mg/kg No observed adverse effect level (mg/kg) NOAEL = 1.5 mg/kg (rat, 13-week, subcutaneous) Margin of Safety NOAEL / SED = 125","page":23,"pdf":"sccp_o_045.pdf","row_type":"noael_study","study_id":"sccp_o_045_noael_009"} |
| SCCS_vision_codex | NOAEL | =500 | mg/kg bw | rat | oral | subchronic | repeated dose toxicity | {"dose":"General toxicity A range-finding study indicated an oral LD50 between 400 and 500 mg/kg bw.","effect":"___________________________________________________________________________ 24 3.3.14. Discussion Physico-chemical specifications 0.5 – 500 mg/ml solutions in acetone/olive oil were stable up to 4 hour study period (maximum deviation from initial concentration ±10%) at room temperature, when stored protected from light and under inert atmosphere. No characterisation of the reaction products in the presence of oxygen. General toxicity A range-finding study indicated an oral LD50 between 400 and 500 mg/kg bw. The NOAEL was set at 10 mg/kg bw/day (oral subchronic study), at 1.5 mg/kg bw/day (rat, 13 week subcutaneous study), at 100 mg/kg bw/day for maternal toxicity and at 250 mg/kg bw/day for embryo-foetal developmental toxicity Irritation / sensitisation The test substance was slightly irritant to rabbit skin and rabbit eye. It was severely irritant to rabbit eye when tested undiluted. It was not a sensitiser to guinea pig skin in a Magnusson Kligman study. It was, however, a strong sensitiser in an LLNA. Dermal absorption Th","page":24,"pdf":"sccp_o_045.pdf","row_type":"noael_study","study_id":"sccp_o_045_noael_011"} |
| SCCS_vision_codex | NOAEL | =10 | mg/kg bw/day | rat | - | - | NOAEL study | {"citation":"Ref.: 10 In the complementary dossier from 2004 the analytical interference between dihydroxyindole and/or its degradation products and the determination of urinary ketones using N-Multi","dose":"These changes occurred in some animals of both sex in the 30 and 100 mg/kg bw/day dose groups, and persisted at the end of the recovery period.","effect":"noted at autopsy, consistent with the microscopic observation of intracellular pigment accumulation in the cortical tubular epithelium. These changes occurred in some animals of both sex in the 30 and 100 mg/kg bw/day dose groups, and persisted at the end of the recovery period. No other histological abnormalities were reported. On the basis of the increased triglyceride and accumulation of pigment in the kidney at 30 and 100 mg/kg bw/day, the study authors concluded that the dose level of 10 mg/kg bw/day was the NOAEL. A significant change in urinalysis (ketones) was observed at 10 mg/kg bw/day, which could be related to the effects seen at higher doses, and therefore the NOEL is 3 mg/kg bw/day. Male rats appear to be more sensitive than females to the effects of this substance. Ref.: 10 In the complementary dossier from 2004 the analytical interference between dihydroxyindole and/or its degradation products and the determination of urinary ketones using N-Multistix SG test strips was investigated. From the results it can be c","page":14,"pdf":"sccp_o_045.pdf","row_type":"noael_study","study_id":"sccp_o_045_noael_001"} |
| SCCS_vision_codex | NOAEL | =3 | mg/kg bw/day | rat | - | - | NOAEL study | {"citation":"Ref.: 10 In the complementary dossier from 2004 the analytical interference between dihydroxyindole and/or its degradation products and the determination of urinary ketones using N-Multi","dose":"some animals of both sex in the 30 and 100 mg/kg bw/day dose groups, and persisted at the end of the recovery period.","effect":"some animals of both sex in the 30 and 100 mg/kg bw/day dose groups, and persisted at the end of the recovery period. No other histological abnormalities were reported. On the basis of the increased triglyceride and accumulation of pigment in the kidney at 30 and 100 mg/kg bw/day, the study authors concluded that the dose level of 10 mg/kg bw/day was the NOAEL. A significant change in urinalysis (ketones) was observed at 10 mg/kg bw/day, which could be related to the effects seen at higher doses, and therefore the NOEL is 3 mg/kg bw/day. Male rats appear to be more sensitive than females to the effects of this substance. Ref.: 10 In the complementary dossier from 2004 the analytical interference between dihydroxyindole and/or its degradation products and the determination of urinary ketones using N-Multistix SG test strips was investigated. From the results it can be concluded that false positive reactions for","page":14,"pdf":"sccp_o_045.pdf","row_type":"noael_study","study_id":"sccp_o_045_noael_002"} |
| SCCS_vision_codex | NOAEL | =1.5 | mg/kg bw/d | - | - | Chronic | NOAEL study | {"citation":"Ref.: 11 3","dose":"and bilirubin (high dose group).","effect":"and bilirubin (high dose group). Increases in the relative weights of spleen, kidney and liver accompanied by pigmentation were seen at the high dose and for the spleen also at 5 mg/kg bw/d (males). Substance-treated animals showed inflammation in the subcutaneous tissues and pigmentation in lymph nodes (pigmentary lymphadenopathy), spleen, liver thyroids. Kidney, adrenal cortex and ovaries, pigmentation was present even in the lowest dose group. In the recovery group the effects were maintained in some cases. No NOEL can be derived. The NOAEL was set by SCCP at 1.5 mg/kg bw/d. Ref.: 11 3.3.5.3. Chronic (> 12 months) toxicity","page":15,"pdf":"sccp_o_045.pdf","row_type":"noael_study","study_id":"sccp_o_045_noael_004"} |
| SCCS_vision_codex | NOAEL | =100 | mg/kg bw/day | rat | - | developmental | reproductive toxicity | {"citation":"Ref.: 17 3","dose":"The mean numbers of corpora lutea, implantation sites, post-implantation loss, live foetuses and foetal bodyweights were similar for control and treated groups.","effect":"macroscopic changes noted above. The mean numbers of corpora lutea, implantation sites, post-implantation loss, live foetuses and foetal bodyweights were similar for control and treated groups. No treatment-related foetal anomalies or malformations were observed. The authors concluded that the test substance was well tolerated by the pregnant female rat at dose levels of 20 and 100 mg/kg bw/day. The dose of 250 mg/kg bw/day was considered to be toxic for the pregnant female but not embryo-toxic or teratogenic. The NOAEL was defined as 100 mg/kg bw/day for maternal toxicity and 250 mg/kg bw/day for embryo-foetal development. Ref.: 17 3.3.8.3 Combined fertility, embryo-foetal and postnatal developmental toxicity Combined fertility, embryo-foetal and postnatal developmental toxicity by subcutaneous route in rats Guideline: / Species/strain: Sprague-Dawley rat, Crl CD (SD) BR strain Group size: 10 males + 10 females Test substance: dihydroxyindole (P39) in saline Batch: Op.3X Purity: 99 % Dose: 0, 5, and 15 mg/kg bw/day Treatment:","page":20,"pdf":"sccp_o_045.pdf","row_type":"noael_study","study_id":"sccp_o_045_noael_006"} |
| SCCS_vision_codex | NOAEL | =15 | mg/kg bw/d | rat | dermal | - | reproductive toxicity | {"citation":"Ref.: 18 3","dose":"Body weight gain and food consumption was decreased in the 15 mg/kg group.","effect":"hts were measured regularly. Pregnant females were allowed to deliver their litters (F1) which were monitored for survival and growth. F0 males and females and F1 pups were sacrificed between day 8 and 10 post partum. Local signs were observed at the injection sites (erythema, scabs, discolouration, nodules, oedema, and thickening). Body weight gain and food consumption was decreased in the 15 mg/kg group. Reproductive performance of the parent as well as survival and growth of the offspring was not affected. The NOAEL was set at 15 mg/kg bw/d. Ref.: 18 3.3.9. Toxicokinetics Toxicokinetic study after single cutaneous application to rats Guideline: / Species/strain: Sprague-Dawley rat Group size: 12 males + 12 females Test substance: [14C] dihydroxyindole (P39) in PEG 300 Batch: 92170 ([14C]-labelled) and Op.3X Dose: 25 mg/kg bw (18.5 MBq/kg), single dermal application Sampling time: 1.8, 2.24, 4.48, 96, 144 and 216 h GLP: in compliance Test batches Op.3X (unlabelled dihydroxyindole, 99% pure) and 92170 (radiolabelled dihydro","page":21,"pdf":"sccp_o_045.pdf","row_type":"noael_study","study_id":"sccp_o_045_noael_007"} |
| SCCS_vision_codex | NOAEL | =0.012 | mg/kg | rat | dermal | 13-week | dermal absorption | {"citation":"Ref.: 23 3","dose":"Safety evaluation (including calculation of the MoS) CALCULATION OF THE MARGIN OF SAFETY Maximum absorption through the skin A (µg/cm2) = 1.0 µg/cm2 Skin Area surface SAS (cm2) = 700 cm2 Dermal absorption per treatment SAS x A x 0.001 = 0.7 mg Typical body weight of human = 60 kg Systemic exposure dose (SED) SAS x A x 0.001/60 = 0.012 mg/kg No o...","effect":"/ml and in water at and above 100 µg/l. It can be concluded that false positive reactions for ketone bodies were induced in the presence of hydroxyindole. Ref.: 23 3.3.13. Safety evaluation (including calculation of the MoS) CALCULATION OF THE MARGIN OF SAFETY Maximum absorption through the skin A (µg/cm2) = 1.0 µg/cm2 Skin Area surface SAS (cm2) = 700 cm2 Dermal absorption per treatment SAS x A x 0.001 = 0.7 mg Typical body weight of human = 60 kg Systemic exposure dose (SED) SAS x A x 0.001/60 = 0.012 mg/kg No observed adverse effect level (mg/kg) NOAEL = 1.5 mg/kg (rat, 13-week, subcutaneous) Margin of Safety NOAEL / SED = 125","page":23,"pdf":"sccp_o_045.pdf","row_type":"noael_study","study_id":"sccp_o_045_noael_008"} |
| SCCS_vision_codex | NOAEL | =1.5 | mg/kg | rat | dermal | 13-week | dermal absorption | {"citation":"Ref.: 23 3","dose":"Safety evaluation (including calculation of the MoS) CALCULATION OF THE MARGIN OF SAFETY Maximum absorption through the skin A (µg/cm2) = 1.0 µg/cm2 Skin Area surface SAS (cm2) = 700 cm2 Dermal absorption per treatment SAS x A x 0.001 = 0.7 mg Typical body weight of human = 60 kg Systemic exposure dose (SED) SAS x A x 0.001/60 = 0.012 mg/kg No o...","effect":"t can be concluded that false positive reactions for ketone bodies were induced in the presence of hydroxyindole. Ref.: 23 3.3.13. Safety evaluation (including calculation of the MoS) CALCULATION OF THE MARGIN OF SAFETY Maximum absorption through the skin A (µg/cm2) = 1.0 µg/cm2 Skin Area surface SAS (cm2) = 700 cm2 Dermal absorption per treatment SAS x A x 0.001 = 0.7 mg Typical body weight of human = 60 kg Systemic exposure dose (SED) SAS x A x 0.001/60 = 0.012 mg/kg No observed adverse effect level (mg/kg) NOAEL = 1.5 mg/kg (rat, 13-week, subcutaneous) Margin of Safety NOAEL / SED = 125","page":23,"pdf":"sccp_o_045.pdf","row_type":"noael_study","study_id":"sccp_o_045_noael_009"} |
| SCCS_vision_codex | NOAEL | =500 | mg/kg bw | rat | oral | subchronic | repeated dose toxicity | {"dose":"General toxicity A range-finding study indicated an oral LD50 between 400 and 500 mg/kg bw.","effect":"___________________________________________________________________________ 24 3.3.14. Discussion Physico-chemical specifications 0.5 – 500 mg/ml solutions in acetone/olive oil were stable up to 4 hour study period (maximum deviation from initial concentration ±10%) at room temperature, when stored protected from light and under inert atmosphere. No characterisation of the reaction products in the presence of oxygen. General toxicity A range-finding study indicated an oral LD50 between 400 and 500 mg/kg bw. The NOAEL was set at 10 mg/kg bw/day (oral subchronic study), at 1.5 mg/kg bw/day (rat, 13 week subcutaneous study), at 100 mg/kg bw/day for maternal toxicity and at 250 mg/kg bw/day for embryo-foetal developmental toxicity Irritation / sensitisation The test substance was slightly irritant to rabbit skin and rabbit eye. It was severely irritant to rabbit eye when tested undiluted. It was not a sensitiser to guinea pig skin in a Magnusson Kligman study. It was, however, a strong sensitiser in an LLNA. Dermal absorption Th","page":24,"pdf":"sccp_o_045.pdf","row_type":"noael_study","study_id":"sccp_o_045_noael_011"} |
| SCCS_vision_codex | NOAEL | =10 | mg/kg bw/day | rat | - | - | NOAEL study | {"citation":"Ref.: 10 In the complementary dossier from 2004 the analytical interference between dihydroxyindole and/or its degradation products and the determination of urinary ketones using N-Multi","dose":"These changes occurred in some animals of both sex in the 30 and 100 mg/kg bw/day dose groups, and persisted at the end of the recovery period.","effect":"noted at autopsy, consistent with the microscopic observation of intracellular pigment accumulation in the cortical tubular epithelium. These changes occurred in some animals of both sex in the 30 and 100 mg/kg bw/day dose groups, and persisted at the end of the recovery period. No other histological abnormalities were reported. On the basis of the increased triglyceride and accumulation of pigment in the kidney at 30 and 100 mg/kg bw/day, the study authors concluded that the dose level of 10 mg/kg bw/day was the NOAEL. A significant change in urinalysis (ketones) was observed at 10 mg/kg bw/day, which could be related to the effects seen at higher doses, and therefore the NOEL is 3 mg/kg bw/day. Male rats appear to be more sensitive than females to the effects of this substance. Ref.: 10 In the complementary dossier from 2004 the analytical interference between dihydroxyindole and/or its degradation products and the determination of urinary ketones using N-Multistix SG test strips was investigated. From the results it can be c","page":14,"pdf":"sccp_o_045.pdf","row_type":"noael_study","study_id":"sccp_o_045_noael_001"} |
| SCCS_vision_codex | NOAEL | =3 | mg/kg bw/day | rat | - | - | NOAEL study | {"citation":"Ref.: 10 In the complementary dossier from 2004 the analytical interference between dihydroxyindole and/or its degradation products and the determination of urinary ketones using N-Multi","dose":"some animals of both sex in the 30 and 100 mg/kg bw/day dose groups, and persisted at the end of the recovery period.","effect":"some animals of both sex in the 30 and 100 mg/kg bw/day dose groups, and persisted at the end of the recovery period. No other histological abnormalities were reported. On the basis of the increased triglyceride and accumulation of pigment in the kidney at 30 and 100 mg/kg bw/day, the study authors concluded that the dose level of 10 mg/kg bw/day was the NOAEL. A significant change in urinalysis (ketones) was observed at 10 mg/kg bw/day, which could be related to the effects seen at higher doses, and therefore the NOEL is 3 mg/kg bw/day. Male rats appear to be more sensitive than females to the effects of this substance. Ref.: 10 In the complementary dossier from 2004 the analytical interference between dihydroxyindole and/or its degradation products and the determination of urinary ketones using N-Multistix SG test strips was investigated. From the results it can be concluded that false positive reactions for","page":14,"pdf":"sccp_o_045.pdf","row_type":"noael_study","study_id":"sccp_o_045_noael_002"} |
| SCCS_vision_codex | NOAEL | =1.5 | mg/kg bw/d | - | - | Chronic | NOAEL study | {"citation":"Ref.: 11 3","dose":"and bilirubin (high dose group).","effect":"and bilirubin (high dose group). Increases in the relative weights of spleen, kidney and liver accompanied by pigmentation were seen at the high dose and for the spleen also at 5 mg/kg bw/d (males). Substance-treated animals showed inflammation in the subcutaneous tissues and pigmentation in lymph nodes (pigmentary lymphadenopathy), spleen, liver thyroids. Kidney, adrenal cortex and ovaries, pigmentation was present even in the lowest dose group. In the recovery group the effects were maintained in some cases. No NOEL can be derived. The NOAEL was set by SCCP at 1.5 mg/kg bw/d. Ref.: 11 3.3.5.3. Chronic (> 12 months) toxicity","page":15,"pdf":"sccp_o_045.pdf","row_type":"noael_study","study_id":"sccp_o_045_noael_004"} |
| SCCS_vision_codex | NOAEL | =100 | mg/kg bw/day | rat | - | developmental | reproductive toxicity | {"citation":"Ref.: 17 3","dose":"The mean numbers of corpora lutea, implantation sites, post-implantation loss, live foetuses and foetal bodyweights were similar for control and treated groups.","effect":"macroscopic changes noted above. The mean numbers of corpora lutea, implantation sites, post-implantation loss, live foetuses and foetal bodyweights were similar for control and treated groups. No treatment-related foetal anomalies or malformations were observed. The authors concluded that the test substance was well tolerated by the pregnant female rat at dose levels of 20 and 100 mg/kg bw/day. The dose of 250 mg/kg bw/day was considered to be toxic for the pregnant female but not embryo-toxic or teratogenic. The NOAEL was defined as 100 mg/kg bw/day for maternal toxicity and 250 mg/kg bw/day for embryo-foetal development. Ref.: 17 3.3.8.3 Combined fertility, embryo-foetal and postnatal developmental toxicity Combined fertility, embryo-foetal and postnatal developmental toxicity by subcutaneous route in rats Guideline: / Species/strain: Sprague-Dawley rat, Crl CD (SD) BR strain Group size: 10 males + 10 females Test substance: dihydroxyindole (P39) in saline Batch: Op.3X Purity: 99 % Dose: 0, 5, and 15 mg/kg bw/day Treatment:","page":20,"pdf":"sccp_o_045.pdf","row_type":"noael_study","study_id":"sccp_o_045_noael_006"} |
| SCCS_vision_codex | NOAEL | =15 | mg/kg bw/d | rat | dermal | - | reproductive toxicity | {"citation":"Ref.: 18 3","dose":"Body weight gain and food consumption was decreased in the 15 mg/kg group.","effect":"hts were measured regularly. Pregnant females were allowed to deliver their litters (F1) which were monitored for survival and growth. F0 males and females and F1 pups were sacrificed between day 8 and 10 post partum. Local signs were observed at the injection sites (erythema, scabs, discolouration, nodules, oedema, and thickening). Body weight gain and food consumption was decreased in the 15 mg/kg group. Reproductive performance of the parent as well as survival and growth of the offspring was not affected. The NOAEL was set at 15 mg/kg bw/d. Ref.: 18 3.3.9. Toxicokinetics Toxicokinetic study after single cutaneous application to rats Guideline: / Species/strain: Sprague-Dawley rat Group size: 12 males + 12 females Test substance: [14C] dihydroxyindole (P39) in PEG 300 Batch: 92170 ([14C]-labelled) and Op.3X Dose: 25 mg/kg bw (18.5 MBq/kg), single dermal application Sampling time: 1.8, 2.24, 4.48, 96, 144 and 216 h GLP: in compliance Test batches Op.3X (unlabelled dihydroxyindole, 99% pure) and 92170 (radiolabelled dihydro","page":21,"pdf":"sccp_o_045.pdf","row_type":"noael_study","study_id":"sccp_o_045_noael_007"} |
| SCCS_vision_codex | NOAEL | =0.012 | mg/kg | rat | dermal | 13-week | dermal absorption | {"citation":"Ref.: 23 3","dose":"Safety evaluation (including calculation of the MoS) CALCULATION OF THE MARGIN OF SAFETY Maximum absorption through the skin A (µg/cm2) = 1.0 µg/cm2 Skin Area surface SAS (cm2) = 700 cm2 Dermal absorption per treatment SAS x A x 0.001 = 0.7 mg Typical body weight of human = 60 kg Systemic exposure dose (SED) SAS x A x 0.001/60 = 0.012 mg/kg No o...","effect":"/ml and in water at and above 100 µg/l. It can be concluded that false positive reactions for ketone bodies were induced in the presence of hydroxyindole. Ref.: 23 3.3.13. Safety evaluation (including calculation of the MoS) CALCULATION OF THE MARGIN OF SAFETY Maximum absorption through the skin A (µg/cm2) = 1.0 µg/cm2 Skin Area surface SAS (cm2) = 700 cm2 Dermal absorption per treatment SAS x A x 0.001 = 0.7 mg Typical body weight of human = 60 kg Systemic exposure dose (SED) SAS x A x 0.001/60 = 0.012 mg/kg No observed adverse effect level (mg/kg) NOAEL = 1.5 mg/kg (rat, 13-week, subcutaneous) Margin of Safety NOAEL / SED = 125","page":23,"pdf":"sccp_o_045.pdf","row_type":"noael_study","study_id":"sccp_o_045_noael_008"} |
| SCCS_vision_codex | NOAEL | =1.5 | mg/kg | rat | dermal | 13-week | dermal absorption | {"citation":"Ref.: 23 3","dose":"Safety evaluation (including calculation of the MoS) CALCULATION OF THE MARGIN OF SAFETY Maximum absorption through the skin A (µg/cm2) = 1.0 µg/cm2 Skin Area surface SAS (cm2) = 700 cm2 Dermal absorption per treatment SAS x A x 0.001 = 0.7 mg Typical body weight of human = 60 kg Systemic exposure dose (SED) SAS x A x 0.001/60 = 0.012 mg/kg No o...","effect":"t can be concluded that false positive reactions for ketone bodies were induced in the presence of hydroxyindole. Ref.: 23 3.3.13. Safety evaluation (including calculation of the MoS) CALCULATION OF THE MARGIN OF SAFETY Maximum absorption through the skin A (µg/cm2) = 1.0 µg/cm2 Skin Area surface SAS (cm2) = 700 cm2 Dermal absorption per treatment SAS x A x 0.001 = 0.7 mg Typical body weight of human = 60 kg Systemic exposure dose (SED) SAS x A x 0.001/60 = 0.012 mg/kg No observed adverse effect level (mg/kg) NOAEL = 1.5 mg/kg (rat, 13-week, subcutaneous) Margin of Safety NOAEL / SED = 125","page":23,"pdf":"sccp_o_045.pdf","row_type":"noael_study","study_id":"sccp_o_045_noael_009"} |
| SCCS_vision_codex | NOAEL | =500 | mg/kg bw | rat | oral | subchronic | repeated dose toxicity | {"dose":"General toxicity A range-finding study indicated an oral LD50 between 400 and 500 mg/kg bw.","effect":"___________________________________________________________________________ 24 3.3.14. Discussion Physico-chemical specifications 0.5 – 500 mg/ml solutions in acetone/olive oil were stable up to 4 hour study period (maximum deviation from initial concentration ±10%) at room temperature, when stored protected from light and under inert atmosphere. No characterisation of the reaction products in the presence of oxygen. General toxicity A range-finding study indicated an oral LD50 between 400 and 500 mg/kg bw. The NOAEL was set at 10 mg/kg bw/day (oral subchronic study), at 1.5 mg/kg bw/day (rat, 13 week subcutaneous study), at 100 mg/kg bw/day for maternal toxicity and at 250 mg/kg bw/day for embryo-foetal developmental toxicity Irritation / sensitisation The test substance was slightly irritant to rabbit skin and rabbit eye. It was severely irritant to rabbit eye when tested undiluted. It was not a sensitiser to guinea pig skin in a Magnusson Kligman study. It was, however, a strong sensitiser in an LLNA. Dermal absorption Th","page":24,"pdf":"sccp_o_045.pdf","row_type":"noael_study","study_id":"sccp_o_045_noael_011"} |
| SCCS_vision_codex | NOAEL | =10 | mg/kg bw/day | rat | - | - | NOAEL study | {"citation":"Ref.: 10 In the complementary dossier from 2004 the analytical interference between dihydroxyindole and/or its degradation products and the determination of urinary ketones using N-Multi","dose":"These changes occurred in some animals of both sex in the 30 and 100 mg/kg bw/day dose groups, and persisted at the end of the recovery period.","effect":"noted at autopsy, consistent with the microscopic observation of intracellular pigment accumulation in the cortical tubular epithelium. These changes occurred in some animals of both sex in the 30 and 100 mg/kg bw/day dose groups, and persisted at the end of the recovery period. No other histological abnormalities were reported. On the basis of the increased triglyceride and accumulation of pigment in the kidney at 30 and 100 mg/kg bw/day, the study authors concluded that the dose level of 10 mg/kg bw/day was the NOAEL. A significant change in urinalysis (ketones) was observed at 10 mg/kg bw/day, which could be related to the effects seen at higher doses, and therefore the NOEL is 3 mg/kg bw/day. Male rats appear to be more sensitive than females to the effects of this substance. Ref.: 10 In the complementary dossier from 2004 the analytical interference between dihydroxyindole and/or its degradation products and the determination of urinary ketones using N-Multistix SG test strips was investigated. From the results it can be c","page":14,"pdf":"sccp_o_045.pdf","row_type":"noael_study","study_id":"sccp_o_045_noael_001"} |
| SCCS_vision_codex | NOAEL | =3 | mg/kg bw/day | rat | - | - | NOAEL study | {"citation":"Ref.: 10 In the complementary dossier from 2004 the analytical interference between dihydroxyindole and/or its degradation products and the determination of urinary ketones using N-Multi","dose":"some animals of both sex in the 30 and 100 mg/kg bw/day dose groups, and persisted at the end of the recovery period.","effect":"some animals of both sex in the 30 and 100 mg/kg bw/day dose groups, and persisted at the end of the recovery period. No other histological abnormalities were reported. On the basis of the increased triglyceride and accumulation of pigment in the kidney at 30 and 100 mg/kg bw/day, the study authors concluded that the dose level of 10 mg/kg bw/day was the NOAEL. A significant change in urinalysis (ketones) was observed at 10 mg/kg bw/day, which could be related to the effects seen at higher doses, and therefore the NOEL is 3 mg/kg bw/day. Male rats appear to be more sensitive than females to the effects of this substance. Ref.: 10 In the complementary dossier from 2004 the analytical interference between dihydroxyindole and/or its degradation products and the determination of urinary ketones using N-Multistix SG test strips was investigated. From the results it can be concluded that false positive reactions for","page":14,"pdf":"sccp_o_045.pdf","row_type":"noael_study","study_id":"sccp_o_045_noael_002"} |
| SCCS_vision_codex | NOAEL | =1.5 | mg/kg bw/d | - | - | Chronic | NOAEL study | {"citation":"Ref.: 11 3","dose":"and bilirubin (high dose group).","effect":"and bilirubin (high dose group). Increases in the relative weights of spleen, kidney and liver accompanied by pigmentation were seen at the high dose and for the spleen also at 5 mg/kg bw/d (males). Substance-treated animals showed inflammation in the subcutaneous tissues and pigmentation in lymph nodes (pigmentary lymphadenopathy), spleen, liver thyroids. Kidney, adrenal cortex and ovaries, pigmentation was present even in the lowest dose group. In the recovery group the effects were maintained in some cases. No NOEL can be derived. The NOAEL was set by SCCP at 1.5 mg/kg bw/d. Ref.: 11 3.3.5.3. Chronic (> 12 months) toxicity","page":15,"pdf":"sccp_o_045.pdf","row_type":"noael_study","study_id":"sccp_o_045_noael_004"} |
| SCCS_vision_codex | NOAEL | =100 | mg/kg bw/day | rat | - | developmental | reproductive toxicity | {"citation":"Ref.: 17 3","dose":"The mean numbers of corpora lutea, implantation sites, post-implantation loss, live foetuses and foetal bodyweights were similar for control and treated groups.","effect":"macroscopic changes noted above. The mean numbers of corpora lutea, implantation sites, post-implantation loss, live foetuses and foetal bodyweights were similar for control and treated groups. No treatment-related foetal anomalies or malformations were observed. The authors concluded that the test substance was well tolerated by the pregnant female rat at dose levels of 20 and 100 mg/kg bw/day. The dose of 250 mg/kg bw/day was considered to be toxic for the pregnant female but not embryo-toxic or teratogenic. The NOAEL was defined as 100 mg/kg bw/day for maternal toxicity and 250 mg/kg bw/day for embryo-foetal development. Ref.: 17 3.3.8.3 Combined fertility, embryo-foetal and postnatal developmental toxicity Combined fertility, embryo-foetal and postnatal developmental toxicity by subcutaneous route in rats Guideline: / Species/strain: Sprague-Dawley rat, Crl CD (SD) BR strain Group size: 10 males + 10 females Test substance: dihydroxyindole (P39) in saline Batch: Op.3X Purity: 99 % Dose: 0, 5, and 15 mg/kg bw/day Treatment:","page":20,"pdf":"sccp_o_045.pdf","row_type":"noael_study","study_id":"sccp_o_045_noael_006"} |
| SCCS_vision_codex | NOAEL | =15 | mg/kg bw/d | rat | dermal | - | reproductive toxicity | {"citation":"Ref.: 18 3","dose":"Body weight gain and food consumption was decreased in the 15 mg/kg group.","effect":"hts were measured regularly. Pregnant females were allowed to deliver their litters (F1) which were monitored for survival and growth. F0 males and females and F1 pups were sacrificed between day 8 and 10 post partum. Local signs were observed at the injection sites (erythema, scabs, discolouration, nodules, oedema, and thickening). Body weight gain and food consumption was decreased in the 15 mg/kg group. Reproductive performance of the parent as well as survival and growth of the offspring was not affected. The NOAEL was set at 15 mg/kg bw/d. Ref.: 18 3.3.9. Toxicokinetics Toxicokinetic study after single cutaneous application to rats Guideline: / Species/strain: Sprague-Dawley rat Group size: 12 males + 12 females Test substance: [14C] dihydroxyindole (P39) in PEG 300 Batch: 92170 ([14C]-labelled) and Op.3X Dose: 25 mg/kg bw (18.5 MBq/kg), single dermal application Sampling time: 1.8, 2.24, 4.48, 96, 144 and 216 h GLP: in compliance Test batches Op.3X (unlabelled dihydroxyindole, 99% pure) and 92170 (radiolabelled dihydro","page":21,"pdf":"sccp_o_045.pdf","row_type":"noael_study","study_id":"sccp_o_045_noael_007"} |
| SCCS_vision_codex | NOAEL | =0.012 | mg/kg | rat | dermal | 13-week | dermal absorption | {"citation":"Ref.: 23 3","dose":"Safety evaluation (including calculation of the MoS) CALCULATION OF THE MARGIN OF SAFETY Maximum absorption through the skin A (µg/cm2) = 1.0 µg/cm2 Skin Area surface SAS (cm2) = 700 cm2 Dermal absorption per treatment SAS x A x 0.001 = 0.7 mg Typical body weight of human = 60 kg Systemic exposure dose (SED) SAS x A x 0.001/60 = 0.012 mg/kg No o...","effect":"/ml and in water at and above 100 µg/l. It can be concluded that false positive reactions for ketone bodies were induced in the presence of hydroxyindole. Ref.: 23 3.3.13. Safety evaluation (including calculation of the MoS) CALCULATION OF THE MARGIN OF SAFETY Maximum absorption through the skin A (µg/cm2) = 1.0 µg/cm2 Skin Area surface SAS (cm2) = 700 cm2 Dermal absorption per treatment SAS x A x 0.001 = 0.7 mg Typical body weight of human = 60 kg Systemic exposure dose (SED) SAS x A x 0.001/60 = 0.012 mg/kg No observed adverse effect level (mg/kg) NOAEL = 1.5 mg/kg (rat, 13-week, subcutaneous) Margin of Safety NOAEL / SED = 125","page":23,"pdf":"sccp_o_045.pdf","row_type":"noael_study","study_id":"sccp_o_045_noael_008"} |
| SCCS_vision_codex | NOAEL | =1.5 | mg/kg | rat | dermal | 13-week | dermal absorption | {"citation":"Ref.: 23 3","dose":"Safety evaluation (including calculation of the MoS) CALCULATION OF THE MARGIN OF SAFETY Maximum absorption through the skin A (µg/cm2) = 1.0 µg/cm2 Skin Area surface SAS (cm2) = 700 cm2 Dermal absorption per treatment SAS x A x 0.001 = 0.7 mg Typical body weight of human = 60 kg Systemic exposure dose (SED) SAS x A x 0.001/60 = 0.012 mg/kg No o...","effect":"t can be concluded that false positive reactions for ketone bodies were induced in the presence of hydroxyindole. Ref.: 23 3.3.13. Safety evaluation (including calculation of the MoS) CALCULATION OF THE MARGIN OF SAFETY Maximum absorption through the skin A (µg/cm2) = 1.0 µg/cm2 Skin Area surface SAS (cm2) = 700 cm2 Dermal absorption per treatment SAS x A x 0.001 = 0.7 mg Typical body weight of human = 60 kg Systemic exposure dose (SED) SAS x A x 0.001/60 = 0.012 mg/kg No observed adverse effect level (mg/kg) NOAEL = 1.5 mg/kg (rat, 13-week, subcutaneous) Margin of Safety NOAEL / SED = 125","page":23,"pdf":"sccp_o_045.pdf","row_type":"noael_study","study_id":"sccp_o_045_noael_009"} |
| SCCS_vision_codex | NOAEL | =500 | mg/kg bw | rat | oral | subchronic | repeated dose toxicity | {"dose":"General toxicity A range-finding study indicated an oral LD50 between 400 and 500 mg/kg bw.","effect":"___________________________________________________________________________ 24 3.3.14. Discussion Physico-chemical specifications 0.5 – 500 mg/ml solutions in acetone/olive oil were stable up to 4 hour study period (maximum deviation from initial concentration ±10%) at room temperature, when stored protected from light and under inert atmosphere. No characterisation of the reaction products in the presence of oxygen. General toxicity A range-finding study indicated an oral LD50 between 400 and 500 mg/kg bw. The NOAEL was set at 10 mg/kg bw/day (oral subchronic study), at 1.5 mg/kg bw/day (rat, 13 week subcutaneous study), at 100 mg/kg bw/day for maternal toxicity and at 250 mg/kg bw/day for embryo-foetal developmental toxicity Irritation / sensitisation The test substance was slightly irritant to rabbit skin and rabbit eye. It was severely irritant to rabbit eye when tested undiluted. It was not a sensitiser to guinea pig skin in a Magnusson Kligman study. It was, however, a strong sensitiser in an LLNA. Dermal absorption Th","page":24,"pdf":"sccp_o_045.pdf","row_type":"noael_study","study_id":"sccp_o_045_noael_011"} |
UnifiedCodex:SCCNFP:beta.noael_studies 12 endpoints
| Source | Endpoint Type | Value | Unit | Species | Route | Duration | Study Type | Reference |
|---|---|---|---|---|---|---|---|---|
| UnifiedCodex:SCCNFP:beta.noael_studies | - | 10 | mg/kg bw/day | rat | oral | 13-week | - | SOURCE_SUBDIR=out_205_en; REPORT_TITLE=OPINION OF THE SCIENTIFIC COMMITTEE ON COSMETIC PRODUCTS AND NON-FOOD PRODUCTS INTENDED FOR CONSUMERS CONCERNING DIHYDROXYINDOLE COLIPA n° : A111; OPINION_NUMBER=SCCNFP/0657/03; COMMITTEE=SCCNFP; REPORT_DATE=18 March 2003; VALUE_TEXT=10; DOSE=A 13-week oral repeat dose study in rats showed intracellular pigment accumulation in the kidneys, elevated serum triglyceride levels and increased urinary ketones, particularly in male rats.; EFFECT=________________________________________ 17 2.12. Conclusions The overall package of tests is adequate and most have been conducted to GLP and appropriate guidelines. The substance was moderately toxic by ingestion. A 13-week oral repeat dose study in rats showed intracellular pigment accumulation in the kidneys, elevated serum triglyceride levels and increased urinary ketones, particularly in male rats. These effects appeared to be treatment- related and did not resolve by the end of a 4-week recovery period. The NOAEL for the pigment accumulation and elevated triglyceride levels was 10 mg/kg bw/day and this was reported by the authors as the NOAEL for the study. However, increased urinary ketones were seen at 10 mg/kg bw/day and it is possible that they provided a sensitive marker of effect. On this basis, a NOEL of 3 mg/kg bw/day is used for the calculation of the Margin of Safety. The NOAEL for maternal toxicity in a teratogenicity study with dosing over the period of organogenesis was an order of magnitude higher than that p; CITATION_NUMBERS=[]; DETAILS_JSON={"cas_number":"3131-52-0","citation":"","dose":"A 13-week oral repeat dose study in rats showed intracellular pigment accumulation in the kidneys, elevated serum triglyceride levels and increased urinary ketones, particularly in male rats.","duration":"13-week","effect":"________________________________________ 17 2.12. Conclusions The overall package of tests is adequate and most have been conducted to GLP and appropriate guidelines. The substance was moderately toxic by ingestion. A 13-week oral repeat dose study in rats showed intracellular pigment accumulation in the kidneys, elevated serum triglyceride levels and increased urinary ketones, particularly in male rats. These effects appeared to be treatment- related and did not resolve by the end of a 4-week recovery period. The NOAEL for the pigment accumulation and elevated triglyceride levels was 10 mg/kg bw/day and this was reported by the authors as the NOAEL for the study. However, increased urinary ketones were seen at 10 mg/kg bw/day and it is possible that they provided a sensitive marker of effect. On this basis, a NOEL of 3 mg/kg bw/day is used for the calculation of the Margin of Safety. The NOAEL for maternal toxicity in a teratogenicity study with dosing over the period of organogenesis was an order of magnitude higher than that p","endpoint":"","ingredient":"5,6-dihydroxyindole","loael_value":"","noael_unit":"mg/kg bw/day","noael_value":"10","page":17,"route":"oral","species":"rat","study_id":"out_205_en_noael_006"} |
| UnifiedCodex:SCCNFP:beta.noael_studies | - | 3 | mg/kg/day | rat | - | 13-week | - | SOURCE_SUBDIR=out_205_en; REPORT_TITLE=OPINION OF THE SCIENTIFIC COMMITTEE ON COSMETIC PRODUCTS AND NON-FOOD PRODUCTS INTENDED FOR CONSUMERS CONCERNING DIHYDROXYINDOLE COLIPA n° : A111; OPINION_NUMBER=SCCNFP/0657/03; COMMITTEE=SCCNFP; REPORT_DATE=18 March 2003; VALUE_TEXT=3; DOSE=The NOEL from a rat 13-week study was 3 mg/kg/day.; EFFECT=ncer Research 42: 3783-3788 (Sept 1982). 12. Miranda, M., Bonfigli, A., Zarivi, O., Manilla, A., Cimini, A.M. and Arcadi, A., Mutagenesis 2: 45-50 (1987). 13. CIT, France. Report No. 12503 RSR (July 1995). 14. L’Oreal, France. Ref: 93/02/03 (Feb 1993) 3. Opinion of the SCCNFP Dihydroxyindole is clastogenic in vitro with and without metabolic activation but is not a bacterial mutagen. One in vivo study (in vivo/in vitro rat hepatocytes) indicates that the compound is not an in vivo somatic cell genotoxic agent. The NOEL from a rat 13-week study was 3 mg/kg/day. In vitro studies indicate a maximum value of 25.65 g/cm2 for percutaneous penetration considering the epidermis, dermis and receptor fluid compartments. Comparing the NOEL with the maximum systemic exposure dose in humans indicated a margin of safety of 10, which is not adequate. The SCCNFP is of the opinion that Dihydroxyindole is not suitable for use in hair dyes. 4. Other considerations / 5. Minority opinions /; CITATION=Ref: 93/02/03 (Feb 1993) 3; CITATION_NUMBERS=[93,2,3,1993]; REFERENCE=Ref: 93/02/03 (Feb 1993) 3; DETAILS_JSON={"cas_number":"3131-52-0","citation":"Ref: 93/02/03 (Feb 1993) 3","dose":"The NOEL from a rat 13-week study was 3 mg/kg/day.","duration":"13-week","effect":"ncer Research 42: 3783-3788 (Sept 1982). 12. Miranda, M., Bonfigli, A., Zarivi, O., Manilla, A., Cimini, A.M. and Arcadi, A., Mutagenesis 2: 45-50 (1987). 13. CIT, France. Report No. 12503 RSR (July 1995). 14. L’Oreal, France. Ref: 93/02/03 (Feb 1993) 3. Opinion of the SCCNFP Dihydroxyindole is clastogenic in vitro with and without metabolic activation but is not a bacterial mutagen. One in vivo study (in vivo/in vitro rat hepatocytes) indicates that the compound is not an in vivo somatic cell genotoxic agent. The NOEL from a rat 13-week study was 3 mg/kg/day. In vitro studies indicate a maximum value of 25.65 \u0004g/cm2 for percutaneous penetration considering the epidermis, dermis and receptor fluid compartments. Comparing the NOEL with the maximum systemic exposure dose in humans indicated a margin of safety of 10, which is not adequate. The SCCNFP is of the opinion that Dihydroxyindole is not suitable for use in hair dyes. 4. Other considerations / 5. Minority opinions /","endpoint":"","ingredient":"5,6-dihydroxyindole","loael_value":"","noael_unit":"mg/kg/day","noael_value":"3","page":18,"route":"","species":"rat","study_id":"out_205_en_noael_010"} |
| UnifiedCodex:SCCNFP:beta.noael_studies | - | 3 | mg/kg/day | rat | - | 13-week | - | SOURCE_SUBDIR=out_205_en; REPORT_TITLE=OPINION OF THE SCIENTIFIC COMMITTEE ON COSMETIC PRODUCTS AND NON-FOOD PRODUCTS INTENDED FOR CONSUMERS CONCERNING DIHYDROXYINDOLE COLIPA n° : A111; OPINION_NUMBER=SCCNFP/0657/03; COMMITTEE=SCCNFP; REPORT_DATE=18 March 2003; VALUE_TEXT=3; DOSE=The NOEL from a rat 13-week study was 3 mg/kg/day.; EFFECT=al, France. Ref: 93/02/03 (Feb 1993) 3. Opinion of the SCCNFP Dihydroxyindole is clastogenic in vitro with and without metabolic activation but is not a bacterial mutagen. One in vivo study (in vivo/in vitro rat hepatocytes) indicates that the compound is not an in vivo somatic cell genotoxic agent. The NOEL from a rat 13-week study was 3 mg/kg/day. In vitro studies indicate a maximum value of 25.65 g/cm2 for percutaneous penetration considering the epidermis, dermis and receptor fluid compartments. Comparing the NOEL with the maximum systemic exposure dose in humans indicated a margin of safety of 10, which is not adequate. The SCCNFP is of the opinion that Dihydroxyindole is not suitable for use in hair dyes. 4. Other considerations / 5. Minority opinions /; CITATION=Ref: 93/02/03 (Feb 1993) 3; CITATION_NUMBERS=[93,2,3,1993]; REFERENCE=Ref: 93/02/03 (Feb 1993) 3; DETAILS_JSON={"cas_number":"3131-52-0","citation":"Ref: 93/02/03 (Feb 1993) 3","dose":"The NOEL from a rat 13-week study was 3 mg/kg/day.","duration":"13-week","effect":"al, France. Ref: 93/02/03 (Feb 1993) 3. Opinion of the SCCNFP Dihydroxyindole is clastogenic in vitro with and without metabolic activation but is not a bacterial mutagen. One in vivo study (in vivo/in vitro rat hepatocytes) indicates that the compound is not an in vivo somatic cell genotoxic agent. The NOEL from a rat 13-week study was 3 mg/kg/day. In vitro studies indicate a maximum value of 25.65 \u0004g/cm2 for percutaneous penetration considering the epidermis, dermis and receptor fluid compartments. Comparing the NOEL with the maximum systemic exposure dose in humans indicated a margin of safety of 10, which is not adequate. The SCCNFP is of the opinion that Dihydroxyindole is not suitable for use in hair dyes. 4. Other considerations / 5. Minority opinions /","endpoint":"","ingredient":"5,6-dihydroxyindole","loael_value":"","noael_unit":"mg/kg/day","noael_value":"3","page":18,"route":"","species":"rat","study_id":"out_205_en_noael_011"} |
| UnifiedCodex:SCCNFP:beta.noael_studies | - | 3 | mg/kg | rat | oral | 13 weeks | - | SOURCE_SUBDIR=out_205_en; REPORT_TITLE=OPINION OF THE SCIENTIFIC COMMITTEE ON COSMETIC PRODUCTS AND NON-FOOD PRODUCTS INTENDED FOR CONSUMERS CONCERNING DIHYDROXYINDOLE COLIPA n° : A111; OPINION_NUMBER=SCCNFP/0657/03; COMMITTEE=SCCNFP; REPORT_DATE=18 March 2003; VALUE_TEXT=3; DOSE=No observed effect level (mg/kg) (rat, 13 weeks gavage) | NOEL | 3 mg/kg; EFFECT=CALCULATION OF THE MARGIN OF SAFETY (Dihydroxyindole) (air oxidative): No observed effect level (mg/kg) (rat, 13 weeks gavage) | NOEL | 3 mg/kg; CITATION_NUMBERS=[]; DETAILS_JSON={"cas_number":"3131-52-0","citation":"","dose":"No observed effect level (mg/kg) (rat, 13 weeks gavage) | NOEL | 3 mg/kg","duration":"13 weeks","effect":"CALCULATION OF THE MARGIN OF SAFETY (Dihydroxyindole) (air oxidative): No observed effect level (mg/kg) (rat, 13 weeks gavage) | NOEL | 3 mg/kg","endpoint":"","ingredient":"5,6-dihydroxyindole","loael_value":"","noael_unit":"mg/kg","noael_value":"3","page":16,"route":"oral","species":"rat","study_id":"out_205_en_noael_012"} |
| UnifiedCodex:SCCNFP:beta.noael_studies | dermal absorption | =3 | mg/kg | rat | oral | 13 weeks | dermal absorption | SOURCE_SUBDIR=out_205_en; REPORT_TITLE=OPINION OF THE SCIENTIFIC COMMITTEE ON COSMETIC PRODUCTS AND NON-FOOD PRODUCTS INTENDED FOR CONSUMERS CONCERNING DIHYDROXYINDOLE COLIPA n° : A111; OPINION_NUMBER=SCCNFP/0657/03; COMMITTEE=SCCNFP; REPORT_DATE=18 March 2003; VALUE_TEXT== 3; DOSE=Safety evaluation CALCULATION OF THE MARGIN OF SAFETY (Dihydroxyindole) (air oxidative) Based on a usage volume of 25 ml, containing at maximum 5 % Maximum absorption through the skin A (µg/cm²) = 25.65 g/cm² Typical body weight of human = 60 kg Skin Area Surface (scalp) SAS = 700 cm² Dermal absorption per treatment SAS x A x 0.001 = 17.96 mg S...; EFFECT=tive for the safety evaluation of COLIPA A111 in hair dye formulations. 2.11. Safety evaluation CALCULATION OF THE MARGIN OF SAFETY (Dihydroxyindole) (air oxidative) Based on a usage volume of 25 ml, containing at maximum 5 % Maximum absorption through the skin A (µg/cm²) = 25.65 g/cm² Typical body weight of human = 60 kg Skin Area Surface (scalp) SAS = 700 cm² Dermal absorption per treatment SAS x A x 0.001 = 17.96 mg Systemic exposure dose (SED) SAS x A x 0.001/ 60 = 0.299 mg/kg No observed effect level (mg/kg) NOEL = 3 mg/kg (rat, 13 weeks gavage) Margin of Safety NOEL / SED = 10; CITATION_NUMBERS=[]; DETAILS_JSON={"cas_number":"3131-52-0","citation":"","dose":"Safety evaluation CALCULATION OF THE MARGIN OF SAFETY (Dihydroxyindole) (air oxidative) Based on a usage volume of 25 ml, containing at maximum 5 % Maximum absorption through the skin A (µg/cm²) = 25.65 \u0001g/cm² Typical body weight of human = 60 kg Skin Area Surface (scalp) SAS = 700 cm² Dermal absorption per treatment SAS x A x 0.001 = 17.96 mg S...","duration":"13 weeks","effect":"tive for the safety evaluation of COLIPA A111 in hair dye formulations. 2.11. Safety evaluation CALCULATION OF THE MARGIN OF SAFETY (Dihydroxyindole) (air oxidative) Based on a usage volume of 25 ml, containing at maximum 5 % Maximum absorption through the skin A (µg/cm²) = 25.65 \u0001g/cm² Typical body weight of human = 60 kg Skin Area Surface (scalp) SAS = 700 cm² Dermal absorption per treatment SAS x A x 0.001 = 17.96 mg Systemic exposure dose (SED) SAS x A x 0.001/ 60 = 0.299 mg/kg No observed effect level (mg/kg) NOEL = 3 mg/kg (rat, 13 weeks gavage) Margin of Safety NOEL / SED = 10","endpoint":"dermal absorption","ingredient":"5,6-dihydroxyindole","loael_value":"","noael_unit":"mg/kg","noael_value":"= 3","page":16,"route":"oral","species":"rat","study_id":"out_205_en_noael_004"} |
| UnifiedCodex:SCCNFP:beta.noael_studies | dermal absorption | =3 | mg/kg | rat | oral | 13 weeks | dermal absorption | SOURCE_SUBDIR=out_205_en; REPORT_TITLE=OPINION OF THE SCIENTIFIC COMMITTEE ON COSMETIC PRODUCTS AND NON-FOOD PRODUCTS INTENDED FOR CONSUMERS CONCERNING DIHYDROXYINDOLE COLIPA n° : A111; OPINION_NUMBER=SCCNFP/0657/03; COMMITTEE=SCCNFP; REPORT_DATE=18 March 2003; VALUE_TEXT== 3; DOSE=Safety evaluation CALCULATION OF THE MARGIN OF SAFETY (Dihydroxyindole) (air oxidative) Based on a usage volume of 25 ml, containing at maximum 5 % Maximum absorption through the skin A (µg/cm²) = 25.65 g/cm² Typical body weight of human = 60 kg Skin Area Surface (scalp) SAS = 700 cm² Dermal absorption per treatment SAS x A x 0.001 = 17.96 mg S...; EFFECT=ye formulations. 2.11. Safety evaluation CALCULATION OF THE MARGIN OF SAFETY (Dihydroxyindole) (air oxidative) Based on a usage volume of 25 ml, containing at maximum 5 % Maximum absorption through the skin A (µg/cm²) = 25.65 g/cm² Typical body weight of human = 60 kg Skin Area Surface (scalp) SAS = 700 cm² Dermal absorption per treatment SAS x A x 0.001 = 17.96 mg Systemic exposure dose (SED) SAS x A x 0.001/ 60 = 0.299 mg/kg No observed effect level (mg/kg) NOEL = 3 mg/kg (rat, 13 weeks gavage) Margin of Safety NOEL / SED = 10; CITATION_NUMBERS=[]; DETAILS_JSON={"cas_number":"3131-52-0","citation":"","dose":"Safety evaluation CALCULATION OF THE MARGIN OF SAFETY (Dihydroxyindole) (air oxidative) Based on a usage volume of 25 ml, containing at maximum 5 % Maximum absorption through the skin A (µg/cm²) = 25.65 \u0001g/cm² Typical body weight of human = 60 kg Skin Area Surface (scalp) SAS = 700 cm² Dermal absorption per treatment SAS x A x 0.001 = 17.96 mg S...","duration":"13 weeks","effect":"ye formulations. 2.11. Safety evaluation CALCULATION OF THE MARGIN OF SAFETY (Dihydroxyindole) (air oxidative) Based on a usage volume of 25 ml, containing at maximum 5 % Maximum absorption through the skin A (µg/cm²) = 25.65 \u0001g/cm² Typical body weight of human = 60 kg Skin Area Surface (scalp) SAS = 700 cm² Dermal absorption per treatment SAS x A x 0.001 = 17.96 mg Systemic exposure dose (SED) SAS x A x 0.001/ 60 = 0.299 mg/kg No observed effect level (mg/kg) NOEL = 3 mg/kg (rat, 13 weeks gavage) Margin of Safety NOEL / SED = 10","endpoint":"dermal absorption","ingredient":"5,6-dihydroxyindole","loael_value":"","noael_unit":"mg/kg","noael_value":"= 3","page":16,"route":"oral","species":"rat","study_id":"out_205_en_noael_005"} |
| UnifiedCodex:SCCNFP:beta.noael_studies | developmental toxicity | 100 | mg/kg bw/day | rat | - | - | developmental toxicity | SOURCE_SUBDIR=out_205_en; REPORT_TITLE=OPINION OF THE SCIENTIFIC COMMITTEE ON COSMETIC PRODUCTS AND NON-FOOD PRODUCTS INTENDED FOR CONSUMERS CONCERNING DIHYDROXYINDOLE COLIPA n° : A111; OPINION_NUMBER=SCCNFP/0657/03; COMMITTEE=SCCNFP; REPORT_DATE=18 March 2003; VALUE_TEXT=100; DOSE=_____________________________ 12 The mean numbers of corpora lutea, implantation sites, post-implantation loss, live foetuses and foetal bodyweights were similar for control and treated groups.; EFFECT=_____________________________ 12 The mean numbers of corpora lutea, implantation sites, post-implantation loss, live foetuses and foetal bodyweights were similar for control and treated groups. No treatment-related foetal anomalies or malformations were observed. The authors concluded that the test substance was well tolerated by the pregnant female rat at dose levels of 20 and 100 mg/kg bw/day. The dose of 250 mg/kg bw/day was considered to be toxic for the pregnant female but not embryo-toxic or teratogenic. The NOAEL was defined as 100 mg/kg bw/day for materno-toxicity and 250 mg/kg bw/day for embryo-foetal development. Ref. : 13 2.7. Toxicokinetics (incl. Percutaneous Absorption) Percutaneous Absorption in vitro Guideline : / Tissue : Human female abdominal skin, dermatomed Method : Franz diffusion cell (static) Test substance : P39, 4.6% in “GEL PROGRESS” formulation, batch number 48.791 Batch no : OP33 (radiochemical purity 93.4%) Dose levels : 1003.9 g/cm2 in the presence of 10.58 mg hair 805.8 g/cm2 in the absence of ha; CITATION=Ref. : 13 2; CITATION_NUMBERS=[13,2]; REFERENCE=Ref. : 13 2; DETAILS_JSON={"cas_number":"3131-52-0","citation":"Ref. : 13 2","dose":"_____________________________ 12 The mean numbers of corpora lutea, implantation sites, post-implantation loss, live foetuses and foetal bodyweights were similar for control and treated groups.","duration":"","effect":"_____________________________ 12 The mean numbers of corpora lutea, implantation sites, post-implantation loss, live foetuses and foetal bodyweights were similar for control and treated groups. No treatment-related foetal anomalies or malformations were observed. The authors concluded that the test substance was well tolerated by the pregnant female rat at dose levels of 20 and 100 mg/kg bw/day. The dose of 250 mg/kg bw/day was considered to be toxic for the pregnant female but not embryo-toxic or teratogenic. The NOAEL was defined as 100 mg/kg bw/day for materno-toxicity and 250 mg/kg bw/day for embryo-foetal development. Ref. : 13 2.7. Toxicokinetics (incl. Percutaneous Absorption) Percutaneous Absorption in vitro Guideline : / Tissue : Human female abdominal skin, dermatomed Method : Franz diffusion cell (static) Test substance : P39, 4.6% in “GEL PROGRESS” formulation, batch number 48.791 Batch no : OP33 (radiochemical purity 93.4%) Dose levels : 1003.9 \u0004g/cm2 in the presence of 10.58 mg hair 805.8 \u0004g/cm2 in the absence of ha","endpoint":"developmental toxicity","ingredient":"5,6-dihydroxyindole","loael_value":"","noael_unit":"mg/kg bw/day","noael_value":"100","page":12,"route":"","species":"rat","study_id":"out_205_en_noael_003"} |
| UnifiedCodex:SCCNFP:beta.noael_studies | developmental toxicity | 10 | mg/kg bw/day | rat | oral | 13-week | developmental toxicity | SOURCE_SUBDIR=out_205_en; REPORT_TITLE=OPINION OF THE SCIENTIFIC COMMITTEE ON COSMETIC PRODUCTS AND NON-FOOD PRODUCTS INTENDED FOR CONSUMERS CONCERNING DIHYDROXYINDOLE COLIPA n° : A111; OPINION_NUMBER=SCCNFP/0657/03; COMMITTEE=SCCNFP; REPORT_DATE=18 March 2003; VALUE_TEXT=10; DOSE=A 13-week oral repeat dose study in rats showed intracellular pigment accumulation in the kidneys, elevated serum triglyceride levels and increased urinary ketones, particularly in male rats.; EFFECT=to GLP and appropriate guidelines. The substance was moderately toxic by ingestion. A 13-week oral repeat dose study in rats showed intracellular pigment accumulation in the kidneys, elevated serum triglyceride levels and increased urinary ketones, particularly in male rats. These effects appeared to be treatment- related and did not resolve by the end of a 4-week recovery period. The NOAEL for the pigment accumulation and elevated triglyceride levels was 10 mg/kg bw/day and this was reported by the authors as the NOAEL for the study. However, increased urinary ketones were seen at 10 mg/kg bw/day and it is possible that they provided a sensitive marker of effect. On this basis, a NOEL of 3 mg/kg bw/day is used for the calculation of the Margin of Safety. The NOAEL for maternal toxicity in a teratogenicity study with dosing over the period of organogenesis was an order of magnitude higher than that produced in the 13-week study and there was no evidence of embryotoxicity, teratogenicity or developmental effects under the conditio; CITATION_NUMBERS=[]; DETAILS_JSON={"cas_number":"3131-52-0","citation":"","dose":"A 13-week oral repeat dose study in rats showed intracellular pigment accumulation in the kidneys, elevated serum triglyceride levels and increased urinary ketones, particularly in male rats.","duration":"13-week","effect":"to GLP and appropriate guidelines. The substance was moderately toxic by ingestion. A 13-week oral repeat dose study in rats showed intracellular pigment accumulation in the kidneys, elevated serum triglyceride levels and increased urinary ketones, particularly in male rats. These effects appeared to be treatment- related and did not resolve by the end of a 4-week recovery period. The NOAEL for the pigment accumulation and elevated triglyceride levels was 10 mg/kg bw/day and this was reported by the authors as the NOAEL for the study. However, increased urinary ketones were seen at 10 mg/kg bw/day and it is possible that they provided a sensitive marker of effect. On this basis, a NOEL of 3 mg/kg bw/day is used for the calculation of the Margin of Safety. The NOAEL for maternal toxicity in a teratogenicity study with dosing over the period of organogenesis was an order of magnitude higher than that produced in the 13-week study and there was no evidence of embryotoxicity, teratogenicity or developmental effects under the conditio","endpoint":"developmental toxicity","ingredient":"5,6-dihydroxyindole","loael_value":"","noael_unit":"mg/kg bw/day","noael_value":"10","page":17,"route":"oral","species":"rat","study_id":"out_205_en_noael_007"} |
| UnifiedCodex:SCCNFP:beta.noael_studies | developmental toxicity | 3 | mg/kg bw/day | rat | - | 4-week | developmental toxicity | SOURCE_SUBDIR=out_205_en; REPORT_TITLE=OPINION OF THE SCIENTIFIC COMMITTEE ON COSMETIC PRODUCTS AND NON-FOOD PRODUCTS INTENDED FOR CONSUMERS CONCERNING DIHYDROXYINDOLE COLIPA n° : A111; OPINION_NUMBER=SCCNFP/0657/03; COMMITTEE=SCCNFP; REPORT_DATE=18 March 2003; VALUE_TEXT=3; DOSE=The NOAEL for the pigment accumulation and elevated triglyceride levels was 10 mg/kg bw/day and this was reported by the authors as the NOAEL for the study.; EFFECT=the kidneys, elevated serum triglyceride levels and increased urinary ketones, particularly in male rats. These effects appeared to be treatment- related and did not resolve by the end of a 4-week recovery period. The NOAEL for the pigment accumulation and elevated triglyceride levels was 10 mg/kg bw/day and this was reported by the authors as the NOAEL for the study. However, increased urinary ketones were seen at 10 mg/kg bw/day and it is possible that they provided a sensitive marker of effect. On this basis, a NOEL of 3 mg/kg bw/day is used for the calculation of the Margin of Safety. The NOAEL for maternal toxicity in a teratogenicity study with dosing over the period of organogenesis was an order of magnitude higher than that produced in the 13-week study and there was no evidence of embryotoxicity, teratogenicity or developmental effects under the conditions of the study. A111 was slightly irritating to the rabbit eye and skin at a concentration of 6%, which is similar to the maximum concentration of 5% for human use. It; CITATION_NUMBERS=[]; DETAILS_JSON={"cas_number":"3131-52-0","citation":"","dose":"The NOAEL for the pigment accumulation and elevated triglyceride levels was 10 mg/kg bw/day and this was reported by the authors as the NOAEL for the study.","duration":"4-week","effect":"the kidneys, elevated serum triglyceride levels and increased urinary ketones, particularly in male rats. These effects appeared to be treatment- related and did not resolve by the end of a 4-week recovery period. The NOAEL for the pigment accumulation and elevated triglyceride levels was 10 mg/kg bw/day and this was reported by the authors as the NOAEL for the study. However, increased urinary ketones were seen at 10 mg/kg bw/day and it is possible that they provided a sensitive marker of effect. On this basis, a NOEL of 3 mg/kg bw/day is used for the calculation of the Margin of Safety. The NOAEL for maternal toxicity in a teratogenicity study with dosing over the period of organogenesis was an order of magnitude higher than that produced in the 13-week study and there was no evidence of embryotoxicity, teratogenicity or developmental effects under the conditions of the study. A111 was slightly irritating to the rabbit eye and skin at a concentration of 6%, which is similar to the maximum concentration of 5% for human use. It","endpoint":"developmental toxicity","ingredient":"5,6-dihydroxyindole","loael_value":"","noael_unit":"mg/kg bw/day","noael_value":"3","page":17,"route":"","species":"rat","study_id":"out_205_en_noael_008"} |
| UnifiedCodex:SCCNFP:beta.noael_studies | developmental toxicity | 3 | mg/kg bw/day | rat | - | 4-week | developmental toxicity | SOURCE_SUBDIR=out_205_en; REPORT_TITLE=OPINION OF THE SCIENTIFIC COMMITTEE ON COSMETIC PRODUCTS AND NON-FOOD PRODUCTS INTENDED FOR CONSUMERS CONCERNING DIHYDROXYINDOLE COLIPA n° : A111; OPINION_NUMBER=SCCNFP/0657/03; COMMITTEE=SCCNFP; REPORT_DATE=18 March 2003; VALUE_TEXT=3; DOSE=The NOAEL for the pigment accumulation and elevated triglyceride levels was 10 mg/kg bw/day and this was reported by the authors as the NOAEL for the study.; EFFECT=articularly in male rats. These effects appeared to be treatment- related and did not resolve by the end of a 4-week recovery period. The NOAEL for the pigment accumulation and elevated triglyceride levels was 10 mg/kg bw/day and this was reported by the authors as the NOAEL for the study. However, increased urinary ketones were seen at 10 mg/kg bw/day and it is possible that they provided a sensitive marker of effect. On this basis, a NOEL of 3 mg/kg bw/day is used for the calculation of the Margin of Safety. The NOAEL for maternal toxicity in a teratogenicity study with dosing over the period of organogenesis was an order of magnitude higher than that produced in the 13-week study and there was no evidence of embryotoxicity, teratogenicity or developmental effects under the conditions of the study. A111 was slightly irritating to the rabbit eye and skin at a concentration of 6%, which is similar to the maximum concentration of 5% for human use. It has not shown evidence of sensitisation reactions. Percutaneous penetration has b; CITATION_NUMBERS=[]; DETAILS_JSON={"cas_number":"3131-52-0","citation":"","dose":"The NOAEL for the pigment accumulation and elevated triglyceride levels was 10 mg/kg bw/day and this was reported by the authors as the NOAEL for the study.","duration":"4-week","effect":"articularly in male rats. These effects appeared to be treatment- related and did not resolve by the end of a 4-week recovery period. The NOAEL for the pigment accumulation and elevated triglyceride levels was 10 mg/kg bw/day and this was reported by the authors as the NOAEL for the study. However, increased urinary ketones were seen at 10 mg/kg bw/day and it is possible that they provided a sensitive marker of effect. On this basis, a NOEL of 3 mg/kg bw/day is used for the calculation of the Margin of Safety. The NOAEL for maternal toxicity in a teratogenicity study with dosing over the period of organogenesis was an order of magnitude higher than that produced in the 13-week study and there was no evidence of embryotoxicity, teratogenicity or developmental effects under the conditions of the study. A111 was slightly irritating to the rabbit eye and skin at a concentration of 6%, which is similar to the maximum concentration of 5% for human use. It has not shown evidence of sensitisation reactions. Percutaneous penetration has b","endpoint":"developmental toxicity","ingredient":"5,6-dihydroxyindole","loael_value":"","noael_unit":"mg/kg bw/day","noael_value":"3","page":17,"route":"","species":"rat","study_id":"out_205_en_noael_009"} |
| UnifiedCodex:SCCNFP:beta.noael_studies | repeated dose toxicity | 10 | mg/kg bw/day | rat | dermal | Sub-chronic | repeated dose toxicity | SOURCE_SUBDIR=out_205_en; REPORT_TITLE=OPINION OF THE SCIENTIFIC COMMITTEE ON COSMETIC PRODUCTS AND NON-FOOD PRODUCTS INTENDED FOR CONSUMERS CONCERNING DIHYDROXYINDOLE COLIPA n° : A111; OPINION_NUMBER=SCCNFP/0657/03; COMMITTEE=SCCNFP; REPORT_DATE=18 March 2003; VALUE_TEXT=10; DOSE=Dihydroxyindole _____________________________________________________________________________________________ 8 On the basis of the increased triglyceride and accumulation of pigment in the kidney at 30 and 100 mg/kg bw/day, the study authors concluded that the dose level of 10 mg/kg bw/day was the NOAEL.; EFFECT=SCCNFP/0657/03, final Evaluation and opinion on : Dihydroxyindole _____________________________________________________________________________________________ 8 On the basis of the increased triglyceride and accumulation of pigment in the kidney at 30 and 100 mg/kg bw/day, the study authors concluded that the dose level of 10 mg/kg bw/day was the NOAEL. A significant change in urinalysis (ketones) was observed at 10 mg/kg bw/day, which could be related to the effects seen at higher doses, and therefore the NOEL is 3 mg/kg bw/day. Male rats appear to be more sensitive than females to the effects of this substance. Ref. : 5 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) Irritancy of 6% solution Guideline : OECD 404 Species/strain : Hyb; CITATION=Ref. : 5 2; CITATION_NUMBERS=[5,2]; REFERENCE=Ref. : 5 2; DETAILS_JSON={"cas_number":"3131-52-0","citation":"Ref. : 5 2","dose":"Dihydroxyindole _____________________________________________________________________________________________ 8 On the basis of the increased triglyceride and accumulation of pigment in the kidney at 30 and 100 mg/kg bw/day, the study authors concluded that the dose level of 10 mg/kg bw/day was the NOAEL.","duration":"Sub-chronic","effect":"SCCNFP/0657/03, final Evaluation and opinion on : Dihydroxyindole _____________________________________________________________________________________________ 8 On the basis of the increased triglyceride and accumulation of pigment in the kidney at 30 and 100 mg/kg bw/day, the study authors concluded that the dose level of 10 mg/kg bw/day was the NOAEL. A significant change in urinalysis (ketones) was observed at 10 mg/kg bw/day, which could be related to the effects seen at higher doses, and therefore the NOEL is 3 mg/kg bw/day. Male rats appear to be more sensitive than females to the effects of this substance. Ref. : 5 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) Irritancy of 6% solution Guideline : OECD 404 Species/strain : Hyb","endpoint":"repeated dose toxicity","ingredient":"5,6-dihydroxyindole","loael_value":"","noael_unit":"mg/kg bw/day","noael_value":"10","page":8,"route":"dermal","species":"rat","study_id":"out_205_en_noael_001"} |
| UnifiedCodex:SCCNFP:beta.noael_studies | repeated dose toxicity | 3 | mg/kg bw/day | rat | dermal | Sub-chronic | repeated dose toxicity | SOURCE_SUBDIR=out_205_en; REPORT_TITLE=OPINION OF THE SCIENTIFIC COMMITTEE ON COSMETIC PRODUCTS AND NON-FOOD PRODUCTS INTENDED FOR CONSUMERS CONCERNING DIHYDROXYINDOLE COLIPA n° : A111; OPINION_NUMBER=SCCNFP/0657/03; COMMITTEE=SCCNFP; REPORT_DATE=18 March 2003; VALUE_TEXT=3; DOSE=Dihydroxyindole _____________________________________________________________________________________________ 8 On the basis of the increased triglyceride and accumulation of pigment in the kidney at 30 and 100 mg/kg bw/day, the study authors concluded that the dose level of 10 mg/kg bw/day was the NOAEL.; EFFECT=SCCNFP/0657/03, final Evaluation and opinion on : Dihydroxyindole _____________________________________________________________________________________________ 8 On the basis of the increased triglyceride and accumulation of pigment in the kidney at 30 and 100 mg/kg bw/day, the study authors concluded that the dose level of 10 mg/kg bw/day was the NOAEL. A significant change in urinalysis (ketones) was observed at 10 mg/kg bw/day, which could be related to the effects seen at higher doses, and therefore the NOEL is 3 mg/kg bw/day. Male rats appear to be more sensitive than females to the effects of this substance. Ref. : 5 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) Irritancy of 6% solution Guideline : OECD 404 Species/strain : Hybrid New Zealand albino rabbit Group size : 6 male Test substance : 5,6-hydroxyindole: 6% in glycerol Batch no : Batch op1E (purity not stated in study report) Dos; CITATION=Ref. : 5 2; CITATION_NUMBERS=[5,2]; REFERENCE=Ref. : 5 2; DETAILS_JSON={"cas_number":"3131-52-0","citation":"Ref. : 5 2","dose":"Dihydroxyindole _____________________________________________________________________________________________ 8 On the basis of the increased triglyceride and accumulation of pigment in the kidney at 30 and 100 mg/kg bw/day, the study authors concluded that the dose level of 10 mg/kg bw/day was the NOAEL.","duration":"Sub-chronic","effect":"SCCNFP/0657/03, final Evaluation and opinion on : Dihydroxyindole _____________________________________________________________________________________________ 8 On the basis of the increased triglyceride and accumulation of pigment in the kidney at 30 and 100 mg/kg bw/day, the study authors concluded that the dose level of 10 mg/kg bw/day was the NOAEL. A significant change in urinalysis (ketones) was observed at 10 mg/kg bw/day, which could be related to the effects seen at higher doses, and therefore the NOEL is 3 mg/kg bw/day. Male rats appear to be more sensitive than females to the effects of this substance. Ref. : 5 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) Irritancy of 6% solution Guideline : OECD 404 Species/strain : Hybrid New Zealand albino rabbit Group size : 6 male Test substance : 5,6-hydroxyindole: 6% in glycerol Batch no : Batch op1E (purity not stated in study report) Dos","endpoint":"repeated dose toxicity","ingredient":"5,6-dihydroxyindole","loael_value":"","noael_unit":"mg/kg bw/day","noael_value":"3","page":8,"route":"dermal","species":"rat","study_id":"out_205_en_noael_002"} |
UnifiedCodex:SCCS_SHADOW:beta.noael_studies 11 endpoints
| Source | Endpoint Type | Value | Unit | Species | Route | Duration | Study Type | Reference |
|---|---|---|---|---|---|---|---|---|
| UnifiedCodex:SCCS_SHADOW:beta.noael_studies | - | 10 | mg/kg bw/day | rat | - | - | - | SOURCE_SUBDIR=sccp_o_045; REPORT_TITLE=Opinion on Dihydroxyindole COLIPA N° A111; OPINION_NUMBER=SCCP/0952/05; COMMITTEE=Scientific Committee on Consumer Products (SCCP); REPORT_DATE=28 March 2006; VALUE_TEXT=10; DOSE=These changes occurred in some animals of both sex in the 30 and 100 mg/kg bw/day dose groups, and persisted at the end of the recovery period.; EFFECT=noted at autopsy, consistent with the microscopic observation of intracellular pigment accumulation in the cortical tubular epithelium. These changes occurred in some animals of both sex in the 30 and 100 mg/kg bw/day dose groups, and persisted at the end of the recovery period. No other histological abnormalities were reported. On the basis of the increased triglyceride and accumulation of pigment in the kidney at 30 and 100 mg/kg bw/day, the study authors concluded that the dose level of 10 mg/kg bw/day was the NOAEL. A significant change in urinalysis (ketones) was observed at 10 mg/kg bw/day, which could be related to the effects seen at higher doses, and therefore the NOEL is 3 mg/kg bw/day. Male rats appear to be more sensitive than females to the effects of this substance. Ref.: 10 In the complementary dossier from 2004 the analytical interference between dihydroxyindole and/or its degradation products and the determination of urinary ketones using N-Multistix SG test strips was investigated. From the results it can be c; CITATION=Ref.: 10 In the complementary dossier from 2004 the analytical interference between dihydroxyindole and/or its degradation products and the determination of urinary ketones using N-Multi; CITATION_NUMBERS=[10,2004]; REFERENCE=Ref.: 10 In the complementary dossier from 2004 the analytical interference between dihydroxyindole and/or its degradation products and the determination of urinary ketones using N-Multi; DETAILS_JSON={"cas_number":"3131-52-0","citation":"Ref.: 10 In the complementary dossier from 2004 the analytical interference between dihydroxyindole and/or its degradation products and the determination of urinary ketones using N-Multi","dose":"These changes occurred in some animals of both sex in the 30 and 100 mg/kg bw/day dose groups, and persisted at the end of the recovery period.","duration":"","effect":"noted at autopsy, consistent with the microscopic observation of intracellular pigment accumulation in the cortical tubular epithelium. These changes occurred in some animals of both sex in the 30 and 100 mg/kg bw/day dose groups, and persisted at the end of the recovery period. No other histological abnormalities were reported. On the basis of the increased triglyceride and accumulation of pigment in the kidney at 30 and 100 mg/kg bw/day, the study authors concluded that the dose level of 10 mg/kg bw/day was the NOAEL. A significant change in urinalysis (ketones) was observed at 10 mg/kg bw/day, which could be related to the effects seen at higher doses, and therefore the NOEL is 3 mg/kg bw/day. Male rats appear to be more sensitive than females to the effects of this substance. Ref.: 10 In the complementary dossier from 2004 the analytical interference between dihydroxyindole and/or its degradation products and the determination of urinary ketones using N-Multistix SG test strips was investigated. From the results it can be c","endpoint":"","ingredient":"Dihydroxyindole (INCI name)","loael_value":"","noael_unit":"mg/kg bw/day","noael_value":"10","page":14,"route":"","species":"rat","study_id":"sccp_o_045_noael_001"} |
| UnifiedCodex:SCCS_SHADOW:beta.noael_studies | - | 3 | mg/kg bw/day | rat | - | - | - | SOURCE_SUBDIR=sccp_o_045; REPORT_TITLE=Opinion on Dihydroxyindole COLIPA N° A111; OPINION_NUMBER=SCCP/0952/05; COMMITTEE=Scientific Committee on Consumer Products (SCCP); REPORT_DATE=28 March 2006; VALUE_TEXT=3; DOSE=some animals of both sex in the 30 and 100 mg/kg bw/day dose groups, and persisted at the end of the recovery period.; EFFECT=some animals of both sex in the 30 and 100 mg/kg bw/day dose groups, and persisted at the end of the recovery period. No other histological abnormalities were reported. On the basis of the increased triglyceride and accumulation of pigment in the kidney at 30 and 100 mg/kg bw/day, the study authors concluded that the dose level of 10 mg/kg bw/day was the NOAEL. A significant change in urinalysis (ketones) was observed at 10 mg/kg bw/day, which could be related to the effects seen at higher doses, and therefore the NOEL is 3 mg/kg bw/day. Male rats appear to be more sensitive than females to the effects of this substance. Ref.: 10 In the complementary dossier from 2004 the analytical interference between dihydroxyindole and/or its degradation products and the determination of urinary ketones using N-Multistix SG test strips was investigated. From the results it can be concluded that false positive reactions for; CITATION=Ref.: 10 In the complementary dossier from 2004 the analytical interference between dihydroxyindole and/or its degradation products and the determination of urinary ketones using N-Multi; CITATION_NUMBERS=[10,2004]; REFERENCE=Ref.: 10 In the complementary dossier from 2004 the analytical interference between dihydroxyindole and/or its degradation products and the determination of urinary ketones using N-Multi; DETAILS_JSON={"cas_number":"3131-52-0","citation":"Ref.: 10 In the complementary dossier from 2004 the analytical interference between dihydroxyindole and/or its degradation products and the determination of urinary ketones using N-Multi","dose":"some animals of both sex in the 30 and 100 mg/kg bw/day dose groups, and persisted at the end of the recovery period.","duration":"","effect":"some animals of both sex in the 30 and 100 mg/kg bw/day dose groups, and persisted at the end of the recovery period. No other histological abnormalities were reported. On the basis of the increased triglyceride and accumulation of pigment in the kidney at 30 and 100 mg/kg bw/day, the study authors concluded that the dose level of 10 mg/kg bw/day was the NOAEL. A significant change in urinalysis (ketones) was observed at 10 mg/kg bw/day, which could be related to the effects seen at higher doses, and therefore the NOEL is 3 mg/kg bw/day. Male rats appear to be more sensitive than females to the effects of this substance. Ref.: 10 In the complementary dossier from 2004 the analytical interference between dihydroxyindole and/or its degradation products and the determination of urinary ketones using N-Multistix SG test strips was investigated. From the results it can be concluded that false positive reactions for","endpoint":"","ingredient":"Dihydroxyindole (INCI name)","loael_value":"","noael_unit":"mg/kg bw/day","noael_value":"3","page":14,"route":"","species":"rat","study_id":"sccp_o_045_noael_002"} |
| UnifiedCodex:SCCS_SHADOW:beta.noael_studies | - | 1.5 | mg/kg bw/d | - | - | Chronic | - | SOURCE_SUBDIR=sccp_o_045; REPORT_TITLE=Opinion on Dihydroxyindole COLIPA N° A111; OPINION_NUMBER=SCCP/0952/05; COMMITTEE=Scientific Committee on Consumer Products (SCCP); REPORT_DATE=28 March 2006; VALUE_TEXT=1.5; DOSE=and bilirubin (high dose group).; EFFECT=and bilirubin (high dose group). Increases in the relative weights of spleen, kidney and liver accompanied by pigmentation were seen at the high dose and for the spleen also at 5 mg/kg bw/d (males). Substance-treated animals showed inflammation in the subcutaneous tissues and pigmentation in lymph nodes (pigmentary lymphadenopathy), spleen, liver thyroids. Kidney, adrenal cortex and ovaries, pigmentation was present even in the lowest dose group. In the recovery group the effects were maintained in some cases. No NOEL can be derived. The NOAEL was set by SCCP at 1.5 mg/kg bw/d. Ref.: 11 3.3.5.3. Chronic (> 12 months) toxicity; CITATION=Ref.: 11 3; CITATION_NUMBERS=[11,3]; REFERENCE=Ref.: 11 3; DETAILS_JSON={"cas_number":"3131-52-0","citation":"Ref.: 11 3","dose":"and bilirubin (high dose group).","duration":"Chronic","effect":"and bilirubin (high dose group). Increases in the relative weights of spleen, kidney and liver accompanied by pigmentation were seen at the high dose and for the spleen also at 5 mg/kg bw/d (males). Substance-treated animals showed inflammation in the subcutaneous tissues and pigmentation in lymph nodes (pigmentary lymphadenopathy), spleen, liver thyroids. Kidney, adrenal cortex and ovaries, pigmentation was present even in the lowest dose group. In the recovery group the effects were maintained in some cases. No NOEL can be derived. The NOAEL was set by SCCP at 1.5 mg/kg bw/d. Ref.: 11 3.3.5.3. Chronic (> 12 months) toxicity","endpoint":"","ingredient":"Dihydroxyindole (INCI name)","loael_value":"","noael_unit":"mg/kg bw/d","noael_value":"1.5","page":15,"route":"","species":"","study_id":"sccp_o_045_noael_004"} |
| UnifiedCodex:SCCS_SHADOW:beta.noael_studies | - | 1.5 | mg/kg bw/d | - | - | Chronic | - | SOURCE_SUBDIR=sccp_o_045; REPORT_TITLE=Opinion on Dihydroxyindole COLIPA N° A111; OPINION_NUMBER=SCCP/0952/05; COMMITTEE=Scientific Committee on Consumer Products (SCCP); REPORT_DATE=28 March 2006; VALUE_TEXT=1.5; DOSE=Increases in the relative weights of spleen, kidney and liver accompanied by pigmentation were seen at the high dose and for the spleen also at 5 mg/kg bw/d (males).; EFFECT=group). Increases in the relative weights of spleen, kidney and liver accompanied by pigmentation were seen at the high dose and for the spleen also at 5 mg/kg bw/d (males). Substance-treated animals showed inflammation in the subcutaneous tissues and pigmentation in lymph nodes (pigmentary lymphadenopathy), spleen, liver thyroids. Kidney, adrenal cortex and ovaries, pigmentation was present even in the lowest dose group. In the recovery group the effects were maintained in some cases. No NOEL can be derived. The NOAEL was set by SCCP at 1.5 mg/kg bw/d. Ref.: 11 3.3.5.3. Chronic (> 12 months) toxicity; CITATION=Ref.: 11 3; CITATION_NUMBERS=[11,3]; REFERENCE=Ref.: 11 3; DETAILS_JSON={"cas_number":"3131-52-0","citation":"Ref.: 11 3","dose":"Increases in the relative weights of spleen, kidney and liver accompanied by pigmentation were seen at the high dose and for the spleen also at 5 mg/kg bw/d (males).","duration":"Chronic","effect":"group). Increases in the relative weights of spleen, kidney and liver accompanied by pigmentation were seen at the high dose and for the spleen also at 5 mg/kg bw/d (males). Substance-treated animals showed inflammation in the subcutaneous tissues and pigmentation in lymph nodes (pigmentary lymphadenopathy), spleen, liver thyroids. Kidney, adrenal cortex and ovaries, pigmentation was present even in the lowest dose group. In the recovery group the effects were maintained in some cases. No NOEL can be derived. The NOAEL was set by SCCP at 1.5 mg/kg bw/d. Ref.: 11 3.3.5.3. Chronic (> 12 months) toxicity","endpoint":"","ingredient":"Dihydroxyindole (INCI name)","loael_value":"","noael_unit":"mg/kg bw/d","noael_value":"1.5","page":15,"route":"","species":"","study_id":"sccp_o_045_noael_005"} |
| UnifiedCodex:SCCS_SHADOW:beta.noael_studies | dermal absorption | =0.012 | mg/kg | rat | dermal | 13-week | dermal absorption | SOURCE_SUBDIR=sccp_o_045; REPORT_TITLE=Opinion on Dihydroxyindole COLIPA N° A111; OPINION_NUMBER=SCCP/0952/05; COMMITTEE=Scientific Committee on Consumer Products (SCCP); REPORT_DATE=28 March 2006; VALUE_TEXT== 0.012; DOSE=Safety evaluation (including calculation of the MoS) CALCULATION OF THE MARGIN OF SAFETY Maximum absorption through the skin A (µg/cm2) = 1.0 µg/cm2 Skin Area surface SAS (cm2) = 700 cm2 Dermal absorption per treatment SAS x A x 0.001 = 0.7 mg Typical body weight of human = 60 kg Systemic exposure dose (SED) SAS x A x 0.001/60 = 0.012 mg/kg No o...; EFFECT=/ml and in water at and above 100 µg/l. It can be concluded that false positive reactions for ketone bodies were induced in the presence of hydroxyindole. Ref.: 23 3.3.13. Safety evaluation (including calculation of the MoS) CALCULATION OF THE MARGIN OF SAFETY Maximum absorption through the skin A (µg/cm2) = 1.0 µg/cm2 Skin Area surface SAS (cm2) = 700 cm2 Dermal absorption per treatment SAS x A x 0.001 = 0.7 mg Typical body weight of human = 60 kg Systemic exposure dose (SED) SAS x A x 0.001/60 = 0.012 mg/kg No observed adverse effect level (mg/kg) NOAEL = 1.5 mg/kg (rat, 13-week, subcutaneous) Margin of Safety NOAEL / SED = 125; CITATION=Ref.: 23 3; CITATION_NUMBERS=[23,3]; REFERENCE=Ref.: 23 3; DETAILS_JSON={"cas_number":"3131-52-0","citation":"Ref.: 23 3","dose":"Safety evaluation (including calculation of the MoS) CALCULATION OF THE MARGIN OF SAFETY Maximum absorption through the skin A (µg/cm2) = 1.0 µg/cm2 Skin Area surface SAS (cm2) = 700 cm2 Dermal absorption per treatment SAS x A x 0.001 = 0.7 mg Typical body weight of human = 60 kg Systemic exposure dose (SED) SAS x A x 0.001/60 = 0.012 mg/kg No o...","duration":"13-week","effect":"/ml and in water at and above 100 µg/l. It can be concluded that false positive reactions for ketone bodies were induced in the presence of hydroxyindole. Ref.: 23 3.3.13. Safety evaluation (including calculation of the MoS) CALCULATION OF THE MARGIN OF SAFETY Maximum absorption through the skin A (µg/cm2) = 1.0 µg/cm2 Skin Area surface SAS (cm2) = 700 cm2 Dermal absorption per treatment SAS x A x 0.001 = 0.7 mg Typical body weight of human = 60 kg Systemic exposure dose (SED) SAS x A x 0.001/60 = 0.012 mg/kg No observed adverse effect level (mg/kg) NOAEL = 1.5 mg/kg (rat, 13-week, subcutaneous) Margin of Safety NOAEL / SED = 125","endpoint":"dermal absorption","ingredient":"Dihydroxyindole (INCI name)","loael_value":"","noael_unit":"mg/kg","noael_value":"= 0.012","page":23,"route":"dermal","species":"rat","study_id":"sccp_o_045_noael_008"} |
| UnifiedCodex:SCCS_SHADOW:beta.noael_studies | dermal absorption | =1.5 | mg/kg | rat | dermal | 13-week | dermal absorption | SOURCE_SUBDIR=sccp_o_045; REPORT_TITLE=Opinion on Dihydroxyindole COLIPA N° A111; OPINION_NUMBER=SCCP/0952/05; COMMITTEE=Scientific Committee on Consumer Products (SCCP); REPORT_DATE=28 March 2006; VALUE_TEXT== 1.5; DOSE=Safety evaluation (including calculation of the MoS) CALCULATION OF THE MARGIN OF SAFETY Maximum absorption through the skin A (µg/cm2) = 1.0 µg/cm2 Skin Area surface SAS (cm2) = 700 cm2 Dermal absorption per treatment SAS x A x 0.001 = 0.7 mg Typical body weight of human = 60 kg Systemic exposure dose (SED) SAS x A x 0.001/60 = 0.012 mg/kg No o...; EFFECT=t can be concluded that false positive reactions for ketone bodies were induced in the presence of hydroxyindole. Ref.: 23 3.3.13. Safety evaluation (including calculation of the MoS) CALCULATION OF THE MARGIN OF SAFETY Maximum absorption through the skin A (µg/cm2) = 1.0 µg/cm2 Skin Area surface SAS (cm2) = 700 cm2 Dermal absorption per treatment SAS x A x 0.001 = 0.7 mg Typical body weight of human = 60 kg Systemic exposure dose (SED) SAS x A x 0.001/60 = 0.012 mg/kg No observed adverse effect level (mg/kg) NOAEL = 1.5 mg/kg (rat, 13-week, subcutaneous) Margin of Safety NOAEL / SED = 125; CITATION=Ref.: 23 3; CITATION_NUMBERS=[23,3]; REFERENCE=Ref.: 23 3; DETAILS_JSON={"cas_number":"3131-52-0","citation":"Ref.: 23 3","dose":"Safety evaluation (including calculation of the MoS) CALCULATION OF THE MARGIN OF SAFETY Maximum absorption through the skin A (µg/cm2) = 1.0 µg/cm2 Skin Area surface SAS (cm2) = 700 cm2 Dermal absorption per treatment SAS x A x 0.001 = 0.7 mg Typical body weight of human = 60 kg Systemic exposure dose (SED) SAS x A x 0.001/60 = 0.012 mg/kg No o...","duration":"13-week","effect":"t can be concluded that false positive reactions for ketone bodies were induced in the presence of hydroxyindole. Ref.: 23 3.3.13. Safety evaluation (including calculation of the MoS) CALCULATION OF THE MARGIN OF SAFETY Maximum absorption through the skin A (µg/cm2) = 1.0 µg/cm2 Skin Area surface SAS (cm2) = 700 cm2 Dermal absorption per treatment SAS x A x 0.001 = 0.7 mg Typical body weight of human = 60 kg Systemic exposure dose (SED) SAS x A x 0.001/60 = 0.012 mg/kg No observed adverse effect level (mg/kg) NOAEL = 1.5 mg/kg (rat, 13-week, subcutaneous) Margin of Safety NOAEL / SED = 125","endpoint":"dermal absorption","ingredient":"Dihydroxyindole (INCI name)","loael_value":"","noael_unit":"mg/kg","noael_value":"= 1.5","page":23,"route":"dermal","species":"rat","study_id":"sccp_o_045_noael_009"} |
| UnifiedCodex:SCCS_SHADOW:beta.noael_studies | dermal absorption | =1.5 | mg/kg | rat | dermal | 13-week | dermal absorption | SOURCE_SUBDIR=sccp_o_045; REPORT_TITLE=Opinion on Dihydroxyindole COLIPA N° A111; OPINION_NUMBER=SCCP/0952/05; COMMITTEE=Scientific Committee on Consumer Products (SCCP); REPORT_DATE=28 March 2006; VALUE_TEXT== 1.5; DOSE=Safety evaluation (including calculation of the MoS) CALCULATION OF THE MARGIN OF SAFETY Maximum absorption through the skin A (µg/cm2) = 1.0 µg/cm2 Skin Area surface SAS (cm2) = 700 cm2 Dermal absorption per treatment SAS x A x 0.001 = 0.7 mg Typical body weight of human = 60 kg Systemic exposure dose (SED) SAS x A x 0.001/60 = 0.012 mg/kg No o...; EFFECT=s were induced in the presence of hydroxyindole. Ref.: 23 3.3.13. Safety evaluation (including calculation of the MoS) CALCULATION OF THE MARGIN OF SAFETY Maximum absorption through the skin A (µg/cm2) = 1.0 µg/cm2 Skin Area surface SAS (cm2) = 700 cm2 Dermal absorption per treatment SAS x A x 0.001 = 0.7 mg Typical body weight of human = 60 kg Systemic exposure dose (SED) SAS x A x 0.001/60 = 0.012 mg/kg No observed adverse effect level (mg/kg) NOAEL = 1.5 mg/kg (rat, 13-week, subcutaneous) Margin of Safety NOAEL / SED = 125; CITATION=Ref.: 23 3; CITATION_NUMBERS=[23,3]; REFERENCE=Ref.: 23 3; DETAILS_JSON={"cas_number":"3131-52-0","citation":"Ref.: 23 3","dose":"Safety evaluation (including calculation of the MoS) CALCULATION OF THE MARGIN OF SAFETY Maximum absorption through the skin A (µg/cm2) = 1.0 µg/cm2 Skin Area surface SAS (cm2) = 700 cm2 Dermal absorption per treatment SAS x A x 0.001 = 0.7 mg Typical body weight of human = 60 kg Systemic exposure dose (SED) SAS x A x 0.001/60 = 0.012 mg/kg No o...","duration":"13-week","effect":"s were induced in the presence of hydroxyindole. Ref.: 23 3.3.13. Safety evaluation (including calculation of the MoS) CALCULATION OF THE MARGIN OF SAFETY Maximum absorption through the skin A (µg/cm2) = 1.0 µg/cm2 Skin Area surface SAS (cm2) = 700 cm2 Dermal absorption per treatment SAS x A x 0.001 = 0.7 mg Typical body weight of human = 60 kg Systemic exposure dose (SED) SAS x A x 0.001/60 = 0.012 mg/kg No observed adverse effect level (mg/kg) NOAEL = 1.5 mg/kg (rat, 13-week, subcutaneous) Margin of Safety NOAEL / SED = 125","endpoint":"dermal absorption","ingredient":"Dihydroxyindole (INCI name)","loael_value":"","noael_unit":"mg/kg","noael_value":"= 1.5","page":23,"route":"dermal","species":"rat","study_id":"sccp_o_045_noael_010"} |
| UnifiedCodex:SCCS_SHADOW:beta.noael_studies | repeated dose toxicity | 10 | mg/kg bw/day | rat | oral | subchronic | repeated dose toxicity | SOURCE_SUBDIR=sccp_o_045; REPORT_TITLE=Opinion on Dihydroxyindole COLIPA N° A111; OPINION_NUMBER=SCCP/0952/05; COMMITTEE=Scientific Committee on Consumer Products (SCCP); REPORT_DATE=28 March 2006; VALUE_TEXT=10; DOSE=In consequence the SCCP sets the NOAEL of the oral subchronic toxicity study at the dose of 10 mg/kg bw/day.; EFFECT=SCCP/0952/05 Opinion on dihydroxyindole ____________________________________________________________________________________________ 15 ketone bodies are obtained in the presence of hydroxyindole (see 3.3.12). In consequence the SCCP sets the NOAEL of the oral subchronic toxicity study at the dose of 10 mg/kg bw/day. 13-week subcutaneous toxicity study in rats Guideline: OECD 408 Species/strain: Sprague-Dawley rat, Crl:CD (SD) BR strain Group size: 16 males + 16 females Test substance: dihydroxyindole (P39) in saline Batch: OP3X Purity: 99 % Dose: 0, 1.5, 5, 15 mg/kg bw/day 3 days/week and 15 mg/kg bw/day, 7 days/week Exposure: 13 weeks Recovery: 4 weeks (6 males + 6 females of the control and the 15 mg/kg (7 days/week) dose group) GLP: in compliance Tes; CITATION_NUMBERS=[]; DETAILS_JSON={"cas_number":"3131-52-0","citation":"","dose":"In consequence the SCCP sets the NOAEL of the oral subchronic toxicity study at the dose of 10 mg/kg bw/day.","duration":"subchronic","effect":"SCCP/0952/05 Opinion on dihydroxyindole ____________________________________________________________________________________________ 15 ketone bodies are obtained in the presence of hydroxyindole (see 3.3.12). In consequence the SCCP sets the NOAEL of the oral subchronic toxicity study at the dose of 10 mg/kg bw/day. 13-week subcutaneous toxicity study in rats Guideline: OECD 408 Species/strain: Sprague-Dawley rat, Crl:CD (SD) BR strain Group size: 16 males + 16 females Test substance: dihydroxyindole (P39) in saline Batch: OP3X Purity: 99 % Dose: 0, 1.5, 5, 15 mg/kg bw/day 3 days/week and 15 mg/kg bw/day, 7 days/week Exposure: 13 weeks Recovery: 4 weeks (6 males + 6 females of the control and the 15 mg/kg (7 days/week) dose group) GLP: in compliance Tes","endpoint":"repeated dose toxicity","ingredient":"Dihydroxyindole (INCI name)","loael_value":"","noael_unit":"mg/kg bw/day","noael_value":"10","page":15,"route":"oral","species":"rat","study_id":"sccp_o_045_noael_003"} |
| UnifiedCodex:SCCS_SHADOW:beta.noael_studies | repeated dose toxicity | 500 | mg/kg bw | rat | oral | subchronic | repeated dose toxicity | SOURCE_SUBDIR=sccp_o_045; REPORT_TITLE=Opinion on Dihydroxyindole COLIPA N° A111; OPINION_NUMBER=SCCP/0952/05; COMMITTEE=Scientific Committee on Consumer Products (SCCP); REPORT_DATE=28 March 2006; VALUE_TEXT=500; DOSE=General toxicity A range-finding study indicated an oral LD50 between 400 and 500 mg/kg bw.; EFFECT=___________________________________________________________________________ 24 3.3.14. Discussion Physico-chemical specifications 0.5 – 500 mg/ml solutions in acetone/olive oil were stable up to 4 hour study period (maximum deviation from initial concentration ±10%) at room temperature, when stored protected from light and under inert atmosphere. No characterisation of the reaction products in the presence of oxygen. General toxicity A range-finding study indicated an oral LD50 between 400 and 500 mg/kg bw. The NOAEL was set at 10 mg/kg bw/day (oral subchronic study), at 1.5 mg/kg bw/day (rat, 13 week subcutaneous study), at 100 mg/kg bw/day for maternal toxicity and at 250 mg/kg bw/day for embryo-foetal developmental toxicity Irritation / sensitisation The test substance was slightly irritant to rabbit skin and rabbit eye. It was severely irritant to rabbit eye when tested undiluted. It was not a sensitiser to guinea pig skin in a Magnusson Kligman study. It was, however, a strong sensitiser in an LLNA. Dermal absorption Th; CITATION_NUMBERS=[]; DETAILS_JSON={"cas_number":"3131-52-0","citation":"","dose":"General toxicity A range-finding study indicated an oral LD50 between 400 and 500 mg/kg bw.","duration":"subchronic","effect":"___________________________________________________________________________ 24 3.3.14. Discussion Physico-chemical specifications 0.5 – 500 mg/ml solutions in acetone/olive oil were stable up to 4 hour study period (maximum deviation from initial concentration ±10%) at room temperature, when stored protected from light and under inert atmosphere. No characterisation of the reaction products in the presence of oxygen. General toxicity A range-finding study indicated an oral LD50 between 400 and 500 mg/kg bw. The NOAEL was set at 10 mg/kg bw/day (oral subchronic study), at 1.5 mg/kg bw/day (rat, 13 week subcutaneous study), at 100 mg/kg bw/day for maternal toxicity and at 250 mg/kg bw/day for embryo-foetal developmental toxicity Irritation / sensitisation The test substance was slightly irritant to rabbit skin and rabbit eye. It was severely irritant to rabbit eye when tested undiluted. It was not a sensitiser to guinea pig skin in a Magnusson Kligman study. It was, however, a strong sensitiser in an LLNA. Dermal absorption Th","endpoint":"repeated dose toxicity","ingredient":"Dihydroxyindole (INCI name)","loael_value":"","noael_unit":"mg/kg bw","noael_value":"500","page":24,"route":"oral","species":"rat","study_id":"sccp_o_045_noael_011"} |
| UnifiedCodex:SCCS_SHADOW:beta.noael_studies | reproductive toxicity | 100 | mg/kg bw/day | rat | - | developmental | reproductive toxicity | SOURCE_SUBDIR=sccp_o_045; REPORT_TITLE=Opinion on Dihydroxyindole COLIPA N° A111; OPINION_NUMBER=SCCP/0952/05; COMMITTEE=Scientific Committee on Consumer Products (SCCP); REPORT_DATE=28 March 2006; VALUE_TEXT=100; DOSE=The mean numbers of corpora lutea, implantation sites, post-implantation loss, live foetuses and foetal bodyweights were similar for control and treated groups.; EFFECT=macroscopic changes noted above. The mean numbers of corpora lutea, implantation sites, post-implantation loss, live foetuses and foetal bodyweights were similar for control and treated groups. No treatment-related foetal anomalies or malformations were observed. The authors concluded that the test substance was well tolerated by the pregnant female rat at dose levels of 20 and 100 mg/kg bw/day. The dose of 250 mg/kg bw/day was considered to be toxic for the pregnant female but not embryo-toxic or teratogenic. The NOAEL was defined as 100 mg/kg bw/day for maternal toxicity and 250 mg/kg bw/day for embryo-foetal development. Ref.: 17 3.3.8.3 Combined fertility, embryo-foetal and postnatal developmental toxicity Combined fertility, embryo-foetal and postnatal developmental toxicity by subcutaneous route in rats Guideline: / Species/strain: Sprague-Dawley rat, Crl CD (SD) BR strain Group size: 10 males + 10 females Test substance: dihydroxyindole (P39) in saline Batch: Op.3X Purity: 99 % Dose: 0, 5, and 15 mg/kg bw/day Treatment:; CITATION=Ref.: 17 3; CITATION_NUMBERS=[17,3]; REFERENCE=Ref.: 17 3; DETAILS_JSON={"cas_number":"3131-52-0","citation":"Ref.: 17 3","dose":"The mean numbers of corpora lutea, implantation sites, post-implantation loss, live foetuses and foetal bodyweights were similar for control and treated groups.","duration":"developmental","effect":"macroscopic changes noted above. The mean numbers of corpora lutea, implantation sites, post-implantation loss, live foetuses and foetal bodyweights were similar for control and treated groups. No treatment-related foetal anomalies or malformations were observed. The authors concluded that the test substance was well tolerated by the pregnant female rat at dose levels of 20 and 100 mg/kg bw/day. The dose of 250 mg/kg bw/day was considered to be toxic for the pregnant female but not embryo-toxic or teratogenic. The NOAEL was defined as 100 mg/kg bw/day for maternal toxicity and 250 mg/kg bw/day for embryo-foetal development. Ref.: 17 3.3.8.3 Combined fertility, embryo-foetal and postnatal developmental toxicity Combined fertility, embryo-foetal and postnatal developmental toxicity by subcutaneous route in rats Guideline: / Species/strain: Sprague-Dawley rat, Crl CD (SD) BR strain Group size: 10 males + 10 females Test substance: dihydroxyindole (P39) in saline Batch: Op.3X Purity: 99 % Dose: 0, 5, and 15 mg/kg bw/day Treatment:","endpoint":"reproductive toxicity","ingredient":"Dihydroxyindole (INCI name)","loael_value":"","noael_unit":"mg/kg bw/day","noael_value":"100","page":20,"route":"","species":"rat","study_id":"sccp_o_045_noael_006"} |
| UnifiedCodex:SCCS_SHADOW:beta.noael_studies | reproductive toxicity | 15 | mg/kg bw/d | rat | dermal | - | reproductive toxicity | SOURCE_SUBDIR=sccp_o_045; REPORT_TITLE=Opinion on Dihydroxyindole COLIPA N° A111; OPINION_NUMBER=SCCP/0952/05; COMMITTEE=Scientific Committee on Consumer Products (SCCP); REPORT_DATE=28 March 2006; VALUE_TEXT=15; DOSE=Body weight gain and food consumption was decreased in the 15 mg/kg group.; EFFECT=hts were measured regularly. Pregnant females were allowed to deliver their litters (F1) which were monitored for survival and growth. F0 males and females and F1 pups were sacrificed between day 8 and 10 post partum. Local signs were observed at the injection sites (erythema, scabs, discolouration, nodules, oedema, and thickening). Body weight gain and food consumption was decreased in the 15 mg/kg group. Reproductive performance of the parent as well as survival and growth of the offspring was not affected. The NOAEL was set at 15 mg/kg bw/d. Ref.: 18 3.3.9. Toxicokinetics Toxicokinetic study after single cutaneous application to rats Guideline: / Species/strain: Sprague-Dawley rat Group size: 12 males + 12 females Test substance: [14C] dihydroxyindole (P39) in PEG 300 Batch: 92170 ([14C]-labelled) and Op.3X Dose: 25 mg/kg bw (18.5 MBq/kg), single dermal application Sampling time: 1.8, 2.24, 4.48, 96, 144 and 216 h GLP: in compliance Test batches Op.3X (unlabelled dihydroxyindole, 99% pure) and 92170 (radiolabelled dihydro; CITATION=Ref.: 18 3; CITATION_NUMBERS=[18,3]; REFERENCE=Ref.: 18 3; DETAILS_JSON={"cas_number":"3131-52-0","citation":"Ref.: 18 3","dose":"Body weight gain and food consumption was decreased in the 15 mg/kg group.","duration":"","effect":"hts were measured regularly. Pregnant females were allowed to deliver their litters (F1) which were monitored for survival and growth. F0 males and females and F1 pups were sacrificed between day 8 and 10 post partum. Local signs were observed at the injection sites (erythema, scabs, discolouration, nodules, oedema, and thickening). Body weight gain and food consumption was decreased in the 15 mg/kg group. Reproductive performance of the parent as well as survival and growth of the offspring was not affected. The NOAEL was set at 15 mg/kg bw/d. Ref.: 18 3.3.9. Toxicokinetics Toxicokinetic study after single cutaneous application to rats Guideline: / Species/strain: Sprague-Dawley rat Group size: 12 males + 12 females Test substance: [14C] dihydroxyindole (P39) in PEG 300 Batch: 92170 ([14C]-labelled) and Op.3X Dose: 25 mg/kg bw (18.5 MBq/kg), single dermal application Sampling time: 1.8, 2.24, 4.48, 96, 144 and 216 h GLP: in compliance Test batches Op.3X (unlabelled dihydroxyindole, 99% pure) and 92170 (radiolabelled dihydro","endpoint":"reproductive toxicity","ingredient":"Dihydroxyindole (INCI name)","loael_value":"","noael_unit":"mg/kg bw/d","noael_value":"15","page":21,"route":"dermal","species":"rat","study_id":"sccp_o_045_noael_007"} |
openFDA substances 4 endpoints
| Source | Endpoint Type | Value | Unit | Species | Route | Duration | Study Type | Reference |
|---|---|---|---|---|---|---|---|---|
| openFDA substances | FDA UNII substance identifier | Z3OC8499KG | UNII | - | - | - | chemical | {"approval_status":null,"molecular_formula":"C8H7NO2","source_table":"substance_identifiers_fda","substance_class":"chemical","unii_code":"Z3OC8499KG"} |
| openFDA substances | FDA UNII substance identifier | Z3OC8499KG | UNII | - | - | - | chemical | {"approval_status":null,"molecular_formula":"C8H7NO2","source_table":"substance_identifiers_fda","substance_class":"chemical","unii_code":"Z3OC8499KG"} |
| openFDA substances | FDA UNII substance identifier | Z3OC8499KG | UNII | - | - | - | chemical | {"approval_status":null,"molecular_formula":"C8H7NO2","source_table":"substance_identifiers_fda","substance_class":"chemical","unii_code":"Z3OC8499KG"} |
| openFDA substances | FDA UNII substance identifier | Z3OC8499KG | UNII | - | - | - | chemical | {"approval_status":null,"molecular_formula":"C8H7NO2","source_table":"substance_identifiers_fda","substance_class":"chemical","unii_code":"Z3OC8499KG"} |