NOAEL Studies
Colorant
Orange 4 (CI 15510) NOAEL Studies
INCI: CI 15510
CAS: 633-96-5
Raw No Observed Adverse Effect Level endpoint records grouped by source. This page does not render calculated Margin of Safety values.
NTP_ICE_endocrine 1 endpoint
| Source | Endpoint Type | Value | Unit | Species | Route | Duration | Study Type | Reference |
|---|---|---|---|---|---|---|---|---|
| NTP_ICE_endocrine | Model Score | 0 | unitless | - | - | - | ARPathway2016; AR Pathway Model, Antagonist | sheet=Integrated_approaches; excel_row=6008; RecordID=ARPathway2016_1427; DatasetName=ARPathway2016; DTXSID=DTXSID0038881; Assay=AR Pathway Model, Antagonist; Endpoint=Model Score; Response=0; Response_Unit=Unitless; URL_CompTox=https://comptox.epa.gov/dashboard/chemical/details/DTXSID0038881 |
SCCNFP_vision_codex 8 endpoints
| Source | Endpoint Type | Value | Unit | Species | Route | Duration | Study Type | Reference |
|---|---|---|---|---|---|---|---|---|
| SCCNFP_vision_codex | NOAEL | =2.5 | mg/kg | rabbit | dermal | Sub-chronic | repeated dose toxicity | {"citation":"Ref.: 14 2","dose":"emopoiesis in the spleen) or other haematological parameters at 2.5 mg/kg/day.","effect":"emopoiesis in the spleen) or other haematological parameters at 2.5 mg/kg/day. In males treated with 10 mg/kg/day, increased organ/body weight ratio in the spleen was noted, which correlated to microscopic findings (extramedullary hemopoiesis in the spleen in all animals treated with 5-10 mg/kg/day. No test article related macroscopic findings were observed during necropsy. With regard to the results obtained this, especially to changes in haematological parameters of males, the No-Observable-Adverse-Effect-Level (NOAEL) of Acid Orange 7 [D&C Orange 4 (C.I. 15510)] was considered to be in the general range around 2.5 mg/kg body weight/day. This dose led to borderline effects on met-hemoglobin and reticulocytes counts without concurrent effects on the spleen. The NOAEL for females could be set to 2.5 mg/kg/body weight/ day. Ref.: 14 2.3.8. Sub-chronic dermal toxicity 3 animals each group (rabbits) were used for this assay. The test material (FDA certified material) was applied to the depilated skin of rabbits. Daily application","page":8,"pdf":"out259_en.pdf","row_type":"noael_study","study_id":"out259_en_noael_001"} |
| SCCNFP_vision_codex | NOAEL | =5 | mg/kg | rat | oral | - | dermal absorption | {"citation":"Ref.: 19 2","dose":"0, 5, 40, 320 mg/kg bw/day.","effect":"r the study: 0, 5, 40, 320 mg/kg bw/day. The animals (22 mated female rats, each concentration) were treated by oral gavage, once daily from day 6 through to day 17 post coitum (last treatment). A standard dose volume of 10 ml/kg bw was used. Females were sacrificed on day 21 post coitum and the foetuses were removed after Caesarean section. The examination of the dams and foetuses was performed in accordance with international recommendations. Results Based on the result, the No-Observable-Adverse-Effect-Level (NOAEL) of Acid Orange 7 [D&C Orange 4 (C.I. 15510)] was considered to be 5 mg/kg body weight/day for the maternal organism and 320 mg/kg body weight for the foetal organism. Ref.: 19 2.7. Toxicokinetics (incl. Percutaneous Absorption) Percutaneous absorption study Guideline : OECD 428 (1999) Test system : pig ear skin (400-500 µm), 12 samples, skin integrity checked by conductivity measurement Contact time : 30 minutes then washing with a shampoo, diffusion monitored during 24 hours Test substance : D&C orang","page":13,"pdf":"out259_en.pdf","row_type":"noael_study","study_id":"out259_en_noael_003"} |
| SCCNFP_vision_codex | NOAEL | =2.5 | mg/kg | rabbit | dermal | Sub-chronic | repeated dose toxicity | {"citation":"Ref.: 14 2","dose":"emopoiesis in the spleen) or other haematological parameters at 2.5 mg/kg/day.","effect":"emopoiesis in the spleen) or other haematological parameters at 2.5 mg/kg/day. In males treated with 10 mg/kg/day, increased organ/body weight ratio in the spleen was noted, which correlated to microscopic findings (extramedullary hemopoiesis in the spleen in all animals treated with 5-10 mg/kg/day. No test article related macroscopic findings were observed during necropsy. With regard to the results obtained this, especially to changes in haematological parameters of males, the No-Observable-Adverse-Effect-Level (NOAEL) of Acid Orange 7 [D&C Orange 4 (C.I. 15510)] was considered to be in the general range around 2.5 mg/kg body weight/day. This dose led to borderline effects on met-hemoglobin and reticulocytes counts without concurrent effects on the spleen. The NOAEL for females could be set to 2.5 mg/kg/body weight/ day. Ref.: 14 2.3.8. Sub-chronic dermal toxicity 3 animals each group (rabbits) were used for this assay. The test material (FDA certified material) was applied to the depilated skin of rabbits. Daily application","page":8,"pdf":"out259_en.pdf","row_type":"noael_study","study_id":"out259_en_noael_001"} |
| SCCNFP_vision_codex | NOAEL | =5 | mg/kg | rat | oral | - | dermal absorption | {"citation":"Ref.: 19 2","dose":"0, 5, 40, 320 mg/kg bw/day.","effect":"r the study: 0, 5, 40, 320 mg/kg bw/day. The animals (22 mated female rats, each concentration) were treated by oral gavage, once daily from day 6 through to day 17 post coitum (last treatment). A standard dose volume of 10 ml/kg bw was used. Females were sacrificed on day 21 post coitum and the foetuses were removed after Caesarean section. The examination of the dams and foetuses was performed in accordance with international recommendations. Results Based on the result, the No-Observable-Adverse-Effect-Level (NOAEL) of Acid Orange 7 [D&C Orange 4 (C.I. 15510)] was considered to be 5 mg/kg body weight/day for the maternal organism and 320 mg/kg body weight for the foetal organism. Ref.: 19 2.7. Toxicokinetics (incl. Percutaneous Absorption) Percutaneous absorption study Guideline : OECD 428 (1999) Test system : pig ear skin (400-500 µm), 12 samples, skin integrity checked by conductivity measurement Contact time : 30 minutes then washing with a shampoo, diffusion monitored during 24 hours Test substance : D&C orang","page":13,"pdf":"out259_en.pdf","row_type":"noael_study","study_id":"out259_en_noael_003"} |
| SCCNFP_vision_codex | NOAEL | =2.5 | mg/kg | rabbit | dermal | Sub-chronic | repeated dose toxicity | {"citation":"Ref.: 14 2","dose":"emopoiesis in the spleen) or other haematological parameters at 2.5 mg/kg/day.","effect":"emopoiesis in the spleen) or other haematological parameters at 2.5 mg/kg/day. In males treated with 10 mg/kg/day, increased organ/body weight ratio in the spleen was noted, which correlated to microscopic findings (extramedullary hemopoiesis in the spleen in all animals treated with 5-10 mg/kg/day. No test article related macroscopic findings were observed during necropsy. With regard to the results obtained this, especially to changes in haematological parameters of males, the No-Observable-Adverse-Effect-Level (NOAEL) of Acid Orange 7 [D&C Orange 4 (C.I. 15510)] was considered to be in the general range around 2.5 mg/kg body weight/day. This dose led to borderline effects on met-hemoglobin and reticulocytes counts without concurrent effects on the spleen. The NOAEL for females could be set to 2.5 mg/kg/body weight/ day. Ref.: 14 2.3.8. Sub-chronic dermal toxicity 3 animals each group (rabbits) were used for this assay. The test material (FDA certified material) was applied to the depilated skin of rabbits. Daily application","page":8,"pdf":"out259_en.pdf","row_type":"noael_study","study_id":"out259_en_noael_001"} |
| SCCNFP_vision_codex | NOAEL | =5 | mg/kg | rat | oral | - | dermal absorption | {"citation":"Ref.: 19 2","dose":"0, 5, 40, 320 mg/kg bw/day.","effect":"r the study: 0, 5, 40, 320 mg/kg bw/day. The animals (22 mated female rats, each concentration) were treated by oral gavage, once daily from day 6 through to day 17 post coitum (last treatment). A standard dose volume of 10 ml/kg bw was used. Females were sacrificed on day 21 post coitum and the foetuses were removed after Caesarean section. The examination of the dams and foetuses was performed in accordance with international recommendations. Results Based on the result, the No-Observable-Adverse-Effect-Level (NOAEL) of Acid Orange 7 [D&C Orange 4 (C.I. 15510)] was considered to be 5 mg/kg body weight/day for the maternal organism and 320 mg/kg body weight for the foetal organism. Ref.: 19 2.7. Toxicokinetics (incl. Percutaneous Absorption) Percutaneous absorption study Guideline : OECD 428 (1999) Test system : pig ear skin (400-500 µm), 12 samples, skin integrity checked by conductivity measurement Contact time : 30 minutes then washing with a shampoo, diffusion monitored during 24 hours Test substance : D&C orang","page":13,"pdf":"out259_en.pdf","row_type":"noael_study","study_id":"out259_en_noael_003"} |
| SCCNFP_vision_codex | NOAEL | =2.5 | mg/kg | rabbit | dermal | Sub-chronic | repeated dose toxicity | {"citation":"Ref.: 14 2","dose":"emopoiesis in the spleen) or other haematological parameters at 2.5 mg/kg/day.","effect":"emopoiesis in the spleen) or other haematological parameters at 2.5 mg/kg/day. In males treated with 10 mg/kg/day, increased organ/body weight ratio in the spleen was noted, which correlated to microscopic findings (extramedullary hemopoiesis in the spleen in all animals treated with 5-10 mg/kg/day. No test article related macroscopic findings were observed during necropsy. With regard to the results obtained this, especially to changes in haematological parameters of males, the No-Observable-Adverse-Effect-Level (NOAEL) of Acid Orange 7 [D&C Orange 4 (C.I. 15510)] was considered to be in the general range around 2.5 mg/kg body weight/day. This dose led to borderline effects on met-hemoglobin and reticulocytes counts without concurrent effects on the spleen. The NOAEL for females could be set to 2.5 mg/kg/body weight/ day. Ref.: 14 2.3.8. Sub-chronic dermal toxicity 3 animals each group (rabbits) were used for this assay. The test material (FDA certified material) was applied to the depilated skin of rabbits. Daily application","page":8,"pdf":"out259_en.pdf","row_type":"noael_study","study_id":"out259_en_noael_001"} |
| SCCNFP_vision_codex | NOAEL | =5 | mg/kg | rat | oral | - | dermal absorption | {"citation":"Ref.: 19 2","dose":"0, 5, 40, 320 mg/kg bw/day.","effect":"r the study: 0, 5, 40, 320 mg/kg bw/day. The animals (22 mated female rats, each concentration) were treated by oral gavage, once daily from day 6 through to day 17 post coitum (last treatment). A standard dose volume of 10 ml/kg bw was used. Females were sacrificed on day 21 post coitum and the foetuses were removed after Caesarean section. The examination of the dams and foetuses was performed in accordance with international recommendations. Results Based on the result, the No-Observable-Adverse-Effect-Level (NOAEL) of Acid Orange 7 [D&C Orange 4 (C.I. 15510)] was considered to be 5 mg/kg body weight/day for the maternal organism and 320 mg/kg body weight for the foetal organism. Ref.: 19 2.7. Toxicokinetics (incl. Percutaneous Absorption) Percutaneous absorption study Guideline : OECD 428 (1999) Test system : pig ear skin (400-500 µm), 12 samples, skin integrity checked by conductivity measurement Contact time : 30 minutes then washing with a shampoo, diffusion monitored during 24 hours Test substance : D&C orang","page":13,"pdf":"out259_en.pdf","row_type":"noael_study","study_id":"out259_en_noael_003"} |
SCCS_vision_codex 48 endpoints
| Source | Endpoint Type | Value | Unit | Species | Route | Duration | Study Type | Reference |
|---|---|---|---|---|---|---|---|---|
| SCCS_vision_codex | NOAEL | =2.5 | mg/kg bw/day | - | - | - | NOAEL study | {"citation":"Ref.: 14 Comment It should be noted that at this dose, some slight early haematological effects (increased met-haemoglobin levels in males and increased reticulocytes count) are already","dose":"hological (extramedullary hemopoiesis in the spleen) or other haematological parameters at 2.5 mg/kg bw/day.","effect":"hological (extramedullary hemopoiesis in the spleen) or other haematological parameters at 2.5 mg/kg bw/day. In males treated with 10 mg/kg bw/day, increased organ/body weight ratio in the spleen was noted, which correlated to microscopic findings (extramedullary hemopoiesis in the spleen in all animals treated with 5-10 mg/kg bw/day. No test article related macroscopic findings were observed during necropsy. With regard to the results obtained this, especially to changes in haematological parameters of males, the No Observed Adverse Effect Level (NOAEL) of Acid Orange 7 was considered to be in the general range around 2.5 mg/kg bw/day. This dose led to borderline effects on met-hemoglobin and reticulocytes counts without concurrent effects on the spleen. The NOAEL for females was set to 2.5 mg/kg bw/ day by the study authors. Ref.: 14 Comment It should be noted that at this dose, some slight early haematological effects (increased met-haemoglobin levels in males and increased reticulocytes count) are already observed. Even if there are in the upper limit","page":18,"pdf":"sccs_o_057.pdf","row_type":"noael_study","study_id":"sccs_o_057_noael_001"} |
| SCCS_vision_codex | NOAEL | =2.5 | mg/kg bw/ day | rabbit | dermal | - | NOAEL study | {"citation":"Ref.: 14 Comment It should be noted that at this dose, some slight early haematological effects (increased met-haemoglobin levels in males and increased reticulocytes count) are already","dose":"xtramedullary hemopoiesis in the spleen in all animals treated with 5-10 mg/kg bw/day.","effect":"xtramedullary hemopoiesis in the spleen in all animals treated with 5-10 mg/kg bw/day. No test article related macroscopic findings were observed during necropsy. With regard to the results obtained this, especially to changes in haematological parameters of males, the No Observed Adverse Effect Level (NOAEL) of Acid Orange 7 was considered to be in the general range around 2.5 mg/kg bw/day. This dose led to borderline effects on met-hemoglobin and reticulocytes counts without concurrent effects on the spleen. The NOAEL for females was set to 2.5 mg/kg bw/ day by the study authors. Ref.: 14 Comment It should be noted that at this dose, some slight early haematological effects (increased met-haemoglobin levels in males and increased reticulocytes count) are already observed. Even if there are in the upper limits of the historical control values, this finding could be test article related. Therefore, the dose of 2.5 mg/kg bw /day is considered as the LOAEL. 90–day dermal toxicity 3 animals each group (rabbits) were used for thi","page":18,"pdf":"sccs_o_057.pdf","row_type":"noael_study","study_id":"sccs_o_057_noael_003"} |
| SCCS_vision_codex | NOAEL | =5 | mg/kg bw/day | human | - | - | NOAEL study | {"citation":"Ref.: 19 3","dose":"Total resorptions were observed in 2 females in the high dose group.","effect":"consumption was also observed. Total resorptions were observed in 2 females in the high dose group. In the females treated at the dose of 40 and 320 mg/kg bw/day, a significant dose-related increased spleen weights was observed. Foetal toxicity: No abnormalities related to the treatment were observed in any foetuses. In the foetuses of group treated at 1000 mg/kg bw/day (dose not used), a slight decrease in the mean body weight was observed. Conclusion Based on the result, the No-Observable-Adverse-Effect-Level (NOAEL) of Acid Orange 7 was considered to be 5 mg/kg bw/day for the maternal organism and 320 mg/kg bw/day for the foetal organism. Ref.: 19 3.3.9. Toxicokinetics No data submitted 3.3.10. Photo-induced toxicity 3.3.10.1. Phototoxicity / photoirritation and photosensitisation No data submitted 3.3.10.2. Phototoxicity / photomutagenicity / photoclastogenicity No data submitted 3.3.11. Human data No data submitted 3.3.12. Special investigations No data submitted","page":24,"pdf":"sccs_o_057.pdf","row_type":"noael_study","study_id":"sccs_o_057_noael_004"} |
| SCCS_vision_codex | NOAEL | =0.83 | mg/kg bw/d | rat | oral | 13-week | dermal absorption | {"dose":"Safety evaluation (including calculation of the MoS) CALCULATION OF THE MARGIN OF SAFETY Acid Orange 7 (non-oxidative conditions) Absorption through the skin A (mean + 2SD) = 3.43 µg/cm² Skin Area surface SAS = 580 cm2 Dermal absorption per treatment SAS x A x 0.001 = 1.99 mg Typical body weight of human = 60 kg Systemic exposure dose (SED) SAS...","effect":"25 3.3.13. Safety evaluation (including calculation of the MoS) CALCULATION OF THE MARGIN OF SAFETY Acid Orange 7 (non-oxidative conditions) Absorption through the skin A (mean + 2SD) = 3.43 µg/cm² Skin Area surface SAS = 580 cm2 Dermal absorption per treatment SAS x A x 0.001 = 1.99 mg Typical body weight of human = 60 kg Systemic exposure dose (SED) SAS x A x 0.001/60 = 0.033 mg/kg bw Lowest Observed Adverse Effect Level LOAEL = 2.5 mg/kg bw/d (13-week, oral, rat) Adjusted by factor 3 = 0.83 mg/kg bw/d MOS NOAEL / SED = 25 3.3.14. Discussion Physico-chemical properties Acid Orange 7 is intended for use in oxidative and non-oxidative hair dye formulations as a direct dye at a maximum concentration of 0.5%. Acid Orange 7 is also permitted to be used as a cosmetic colorant, listed as CI 15510 in Annex IV of the EU Cosmetic Directive. The content of Acid Orange 7 in the test materials has not been measured using a standard reference material. The colour content (measured as HPLC peak area?) of various batches, reported in","page":25,"pdf":"sccs_o_057.pdf","row_type":"noael_study","study_id":"sccs_o_057_noael_005"} |
| SCCS_vision_codex | NOAEL | =2.5 | mg/kg bw/d | rat | oral | 13-weeks | NOAEL study | {"dose":"The NOAEL of a 13-weeks oral toxicity study in rats, was set to 2.5 mg/kg bw/d by the study authors.","effect":"reference material. The colour content (measured as HPLC peak area?) of various batches, reported in the table above, may not represent Acid Orange 7 content. Purity and impurities of all batches is not documented. Colour content in one of the batches is only 91%, but impurities in this batch are not reported. The stability in of Acid Orange 7 in typical hair dye formulations is not reported. The stability in an oxidative environment has not been demonstrated. Toxicity Acid Orange 7 is of low acute toxicity. The NOAEL of a 13-weeks oral toxicity study in rats, was set to 2.5 mg/kg bw/d by the study authors. It should be noted that at this dose, some slight early haematological effects (increased met-haemoglobin levels in males and increased reticulocytes count) are already observed. Even if they are in the upper limits of the historical control values, this finding could be test article related. Therefore the dose of 2.5 mg/kg bw/d should be considered as a LOAEL. Studies of effects on embryo-foetal development lead to a NOAEL","page":25,"pdf":"sccs_o_057.pdf","row_type":"noael_study","study_id":"sccs_o_057_noael_006"} |
| SCCS_vision_codex | NOAEL | =5 | mg/kg bw/d | rat | oral | 13-weeks | dermal absorption | {"dose":"NOAEL of a 13-weeks oral toxicity study in rats, was set to 2.5 mg/kg bw/d by the study authors.","effect":"NOAEL of a 13-weeks oral toxicity study in rats, was set to 2.5 mg/kg bw/d by the study authors. It should be noted that at this dose, some slight early haematological effects (increased met-haemoglobin levels in males and increased reticulocytes count) are already observed. Even if they are in the upper limits of the historical control values, this finding could be test article related. Therefore the dose of 2.5 mg/kg bw/d should be considered as a LOAEL. Studies of effects on embryo-foetal development lead to a NOAEL of 5 mg/kg bw/d for maternal toxicity and 320 mg/kg bw/d for foetal toxicity. Irritation and sensitization The assessment of skin and eye irritation does not complying with the current standards; nevertheless, there is no reason to ask for a repetition of these studies. According to the studies available, Acid Orange 7 is not irritating to rabbit skin and not a sensitiser. Percutaneous absorption Under the reported conditions, the dermal absorption of Acid Orange 7 is 1.13 ± 1.15 µg/cm² or 1.25 ± 1.20% (mean v","page":25,"pdf":"sccs_o_057.pdf","row_type":"noael_study","study_id":"sccs_o_057_noael_007"} |
| SCCS_vision_codex | NOAEL | =2.5 | mg/kg bw/day | - | - | - | NOAEL study | {"citation":"Ref.: 14 SCCS comment It should be noted that at this dose, some slight early haematological effects (increased met-haemoglobin levels in males and increased reticulocytes count) have be","dose":"ramedullary hemopoiesis in the spleen) or other haematological parameters at 2.5 mg/kg bw/day.","effect":"ramedullary hemopoiesis in the spleen) or other haematological parameters at 2.5 mg/kg bw/day. In males treated with 10 mg/kg bw/day, increased organ/body weight ratio in the spleen was noted, which correlated to microscopic findings (extramedullary hemopoiesis) in the spleen in all animals treated with 5-10 mg/kg bw/day. No test article-related macroscopic findings were observed during necropsy. With regard to the results obtained in this study, especially to changes in the haematological parameters of males, the No Observed Adverse Effect Level (NOAEL) of Acid Orange 7 was considered to be in the general range of around 2.5 mg/kg bw/day. This dose led to borderline effects on met-hemoglobin and reticulocytes counts without concurrent effects on the spleen. Conclusion The NOAEL for females was set to 2.5 mg/kg bw/ day by the study authors. Ref.: 14 SCCS comment It should be noted that at this dose, some slight early haematological effects (increased met-haemoglobin levels in males and increased reticulocytes count) have been observed. Even if they are","page":21,"pdf":"sccs_o_158.pdf","row_type":"noael_study","study_id":"sccs_o_158_noael_001"} |
| SCCS_vision_codex | NOAEL | =2.5 | mg/kg bw/ day | rabbit | dermal | - | NOAEL study | {"citation":"Ref.: 14 SCCS comment It should be noted that at this dose, some slight early haematological effects (increased met-haemoglobin levels in males and increased reticulocytes count) have be","dose":"the spleen in all animals treated with 5-10 mg/kg bw/day.","effect":"the spleen in all animals treated with 5-10 mg/kg bw/day. No test article-related macroscopic findings were observed during necropsy. With regard to the results obtained in this study, especially to changes in the haematological parameters of males, the No Observed Adverse Effect Level (NOAEL) of Acid Orange 7 was considered to be in the general range of around 2.5 mg/kg bw/day. This dose led to borderline effects on met-hemoglobin and reticulocytes counts without concurrent effects on the spleen. Conclusion The NOAEL for females was set to 2.5 mg/kg bw/ day by the study authors. Ref.: 14 SCCS comment It should be noted that at this dose, some slight early haematological effects (increased met-haemoglobin levels in males and increased reticulocytes count) have been observed. Even if they are in the upper limits of the historical control values, this finding could be test article related. Therefore, the dose of 2.5 mg/kg bw /day is considered as the LOAEL. 90–day dermal toxicity 3 animals per group (rabbits) were used for t","page":21,"pdf":"sccs_o_158.pdf","row_type":"noael_study","study_id":"sccs_o_158_noael_003"} |
| SCCS_vision_codex | NOAEL | =5 | mg/kg bw/day | human | - | - | NOAEL study | {"citation":"Ref.: 19 3","dose":"Total resorptions were observed in 2 females in the high dose group.","effect":"umption was also observed. Total resorptions were observed in 2 females in the high dose group. In the females treated at the dose of 40 and 320 mg/kg bw/day, a significant dose-related increased spleen weights was observed. Foetal toxicity: No abnormalities related to the treatment were observed in any foetuses. In the foetuses of the group treated at 1000 mg/kg bw/day (dose not used), a slight decrease in the mean body weight was observed. Conclusion Based on the result, the No-Observable-Adverse-Effect-Level (NOAEL) of Acid Orange 7 was considered to be 5 mg/kg bw/day for the maternal organism and 320 mg/kg bw/day for the foetal organism. Ref.: 19 3.3.9. Toxicokinetics No data submitted 3.3.10. Photo-induced toxicity 3.3.10.1. Phototoxicity / photoirritation and photosensitisation No data submitted 3.3.10.2. Phototoxicity / photomutagenicity / photoclastogenicity No data submitted 3.3.11. Human data No data submitted 3.3.12. Special investigations No data submitted","page":27,"pdf":"sccs_o_158.pdf","row_type":"noael_study","study_id":"sccs_o_158_noael_004"} |
| SCCS_vision_codex | NOAEL | =50 | % | rat | oral | 13-week | dermal absorption | {"dose":"ncluding calculation of the MoS) CALCULATION OF THE MARGIN OF SAFETY Acid Orange 7 (non-oxidative conditions) Absorption through the skin A (mean + 1 SD) = 0.25 µg/cm² Skin Area surface SAS = 580 cm2 Dermal absorption per treatment SAS x A x 0.001 = 0.145 mg Typical body weight of human = 60 kg Systemic exposure dose (SED) SAS x A x 0.001/60 = 0...","effect":"ncluding calculation of the MoS) CALCULATION OF THE MARGIN OF SAFETY Acid Orange 7 (non-oxidative conditions) Absorption through the skin A (mean + 1 SD) = 0.25 µg/cm² Skin Area surface SAS = 580 cm2 Dermal absorption per treatment SAS x A x 0.001 = 0.145 mg Typical body weight of human = 60 kg Systemic exposure dose (SED) SAS x A x 0.001/60 = 0.0024 mg/kg bw Lowest Observed Adverse Effect Level LOAEL = 2.5 mg/kg bw/d (13-week, oral, rat) Adjusted by factor 3 = 0.83 mg/kg bw/d Bioavailability 50% = 0.415 MoS NOAEL / SED = 172 3.3.14. Discussion Physico-chemical properties Acid Orange 7 is intended for use in oxidative and non-oxidative hair dye formulations as a direct dye at a maximum concentration of 0.5%. Acid Orange 7 is also permitted to be used as a cosmetic colorant, listed as CI 15510 in Annex IV of the EU Cosmetic Directive. The reported Acid Orange 7 content in various batches of test material should be considered semi-quantitative determination, because the content is determined only in terms of colour content","page":28,"pdf":"sccs_o_158.pdf","row_type":"noael_study","study_id":"sccs_o_158_noael_005"} |
| SCCS_vision_codex | NOAEL | =2.5 | mg/kg bw/d | rat | oral | 13-week | NOAEL study | {"dose":"The NOAEL of a 13-week oral toxicity study in rats was set to 2.5 mg/kg bw/d by the study authors.","effect":"ion, because the content is determined only in terms of colour content. Thus, impurities with the same colour (chromophore groups) will also be measured together with the active substance. Impurities in one of the batches of Acid Orange 7 (colour content 91%) were not reported. Stability of Acid Orange 7 under oxidative conditions of use has not been reported. In addition, the stability in of Acid Orange 7 in typical hair dye formulations is not reported. Toxicity Acid Orange 7 is of low acute oral toxicity. The NOAEL of a 13-week oral toxicity study in rats was set to 2.5 mg/kg bw/d by the study authors. It should be noted that at this dose, some slight early haematological effects (increased met-haemoglobin levels in males and increased reticulocytes count) have already been observed. Even if these are in the upper limits of the historical control values, this finding could be test article-related. Therefore the dose of 2.5 mg/kg bw/d should be considered as a LOAEL. Studies of effects on embryo-foetal development lead to a N","page":28,"pdf":"sccs_o_158.pdf","row_type":"noael_study","study_id":"sccs_o_158_noael_006"} |
| SCCS_vision_codex | NOAEL | =5 | mg/kg bw/d | rat | oral | 13-week | dermal absorption | {"dose":"L of a 13-week oral toxicity study in rats was set to 2.5 mg/kg bw/d by the study authors.","effect":"L of a 13-week oral toxicity study in rats was set to 2.5 mg/kg bw/d by the study authors. It should be noted that at this dose, some slight early haematological effects (increased met-haemoglobin levels in males and increased reticulocytes count) have already been observed. Even if these are in the upper limits of the historical control values, this finding could be test article-related. Therefore the dose of 2.5 mg/kg bw/d should be considered as a LOAEL. Studies of effects on embryo-foetal development lead to a NOAEL of 5 mg/kg bw/d for maternal toxicity and 320 mg/kg bw/d for foetal toxicity. Irritation and sensitisation The assessment of skin and eye irritation does not comply with the current standards. According to the studies available, Acid Orange 7 is considered a mild skin irritant. Based on the data submitted, eye irritation potential cannot be evaluated. Based on the result in the available studies, Acid Orange 7 is not a skin sensitiser. Percutaneous absorption For the calculation of MoS, the mean+ 1 SD dermal ab","page":28,"pdf":"sccs_o_158.pdf","row_type":"noael_study","study_id":"sccs_o_158_noael_007"} |
| SCCS_vision_codex | NOAEL | =2.5 | mg/kg bw/day | - | - | - | NOAEL study | {"citation":"Ref.: 14 Comment It should be noted that at this dose, some slight early haematological effects (increased met-haemoglobin levels in males and increased reticulocytes count) are already","dose":"hological (extramedullary hemopoiesis in the spleen) or other haematological parameters at 2.5 mg/kg bw/day.","effect":"hological (extramedullary hemopoiesis in the spleen) or other haematological parameters at 2.5 mg/kg bw/day. In males treated with 10 mg/kg bw/day, increased organ/body weight ratio in the spleen was noted, which correlated to microscopic findings (extramedullary hemopoiesis in the spleen in all animals treated with 5-10 mg/kg bw/day. No test article related macroscopic findings were observed during necropsy. With regard to the results obtained this, especially to changes in haematological parameters of males, the No Observed Adverse Effect Level (NOAEL) of Acid Orange 7 was considered to be in the general range around 2.5 mg/kg bw/day. This dose led to borderline effects on met-hemoglobin and reticulocytes counts without concurrent effects on the spleen. The NOAEL for females was set to 2.5 mg/kg bw/ day by the study authors. Ref.: 14 Comment It should be noted that at this dose, some slight early haematological effects (increased met-haemoglobin levels in males and increased reticulocytes count) are already observed. Even if there are in the upper limit","page":18,"pdf":"sccs_o_057.pdf","row_type":"noael_study","study_id":"sccs_o_057_noael_001"} |
| SCCS_vision_codex | NOAEL | =2.5 | mg/kg bw/ day | rabbit | dermal | - | NOAEL study | {"citation":"Ref.: 14 Comment It should be noted that at this dose, some slight early haematological effects (increased met-haemoglobin levels in males and increased reticulocytes count) are already","dose":"xtramedullary hemopoiesis in the spleen in all animals treated with 5-10 mg/kg bw/day.","effect":"xtramedullary hemopoiesis in the spleen in all animals treated with 5-10 mg/kg bw/day. No test article related macroscopic findings were observed during necropsy. With regard to the results obtained this, especially to changes in haematological parameters of males, the No Observed Adverse Effect Level (NOAEL) of Acid Orange 7 was considered to be in the general range around 2.5 mg/kg bw/day. This dose led to borderline effects on met-hemoglobin and reticulocytes counts without concurrent effects on the spleen. The NOAEL for females was set to 2.5 mg/kg bw/ day by the study authors. Ref.: 14 Comment It should be noted that at this dose, some slight early haematological effects (increased met-haemoglobin levels in males and increased reticulocytes count) are already observed. Even if there are in the upper limits of the historical control values, this finding could be test article related. Therefore, the dose of 2.5 mg/kg bw /day is considered as the LOAEL. 90–day dermal toxicity 3 animals each group (rabbits) were used for thi","page":18,"pdf":"sccs_o_057.pdf","row_type":"noael_study","study_id":"sccs_o_057_noael_003"} |
| SCCS_vision_codex | NOAEL | =5 | mg/kg bw/day | human | - | - | NOAEL study | {"citation":"Ref.: 19 3","dose":"Total resorptions were observed in 2 females in the high dose group.","effect":"consumption was also observed. Total resorptions were observed in 2 females in the high dose group. In the females treated at the dose of 40 and 320 mg/kg bw/day, a significant dose-related increased spleen weights was observed. Foetal toxicity: No abnormalities related to the treatment were observed in any foetuses. In the foetuses of group treated at 1000 mg/kg bw/day (dose not used), a slight decrease in the mean body weight was observed. Conclusion Based on the result, the No-Observable-Adverse-Effect-Level (NOAEL) of Acid Orange 7 was considered to be 5 mg/kg bw/day for the maternal organism and 320 mg/kg bw/day for the foetal organism. Ref.: 19 3.3.9. Toxicokinetics No data submitted 3.3.10. Photo-induced toxicity 3.3.10.1. Phototoxicity / photoirritation and photosensitisation No data submitted 3.3.10.2. Phototoxicity / photomutagenicity / photoclastogenicity No data submitted 3.3.11. Human data No data submitted 3.3.12. Special investigations No data submitted","page":24,"pdf":"sccs_o_057.pdf","row_type":"noael_study","study_id":"sccs_o_057_noael_004"} |
| SCCS_vision_codex | NOAEL | =0.83 | mg/kg bw/d | rat | oral | 13-week | dermal absorption | {"dose":"Safety evaluation (including calculation of the MoS) CALCULATION OF THE MARGIN OF SAFETY Acid Orange 7 (non-oxidative conditions) Absorption through the skin A (mean + 2SD) = 3.43 µg/cm² Skin Area surface SAS = 580 cm2 Dermal absorption per treatment SAS x A x 0.001 = 1.99 mg Typical body weight of human = 60 kg Systemic exposure dose (SED) SAS...","effect":"25 3.3.13. Safety evaluation (including calculation of the MoS) CALCULATION OF THE MARGIN OF SAFETY Acid Orange 7 (non-oxidative conditions) Absorption through the skin A (mean + 2SD) = 3.43 µg/cm² Skin Area surface SAS = 580 cm2 Dermal absorption per treatment SAS x A x 0.001 = 1.99 mg Typical body weight of human = 60 kg Systemic exposure dose (SED) SAS x A x 0.001/60 = 0.033 mg/kg bw Lowest Observed Adverse Effect Level LOAEL = 2.5 mg/kg bw/d (13-week, oral, rat) Adjusted by factor 3 = 0.83 mg/kg bw/d MOS NOAEL / SED = 25 3.3.14. Discussion Physico-chemical properties Acid Orange 7 is intended for use in oxidative and non-oxidative hair dye formulations as a direct dye at a maximum concentration of 0.5%. Acid Orange 7 is also permitted to be used as a cosmetic colorant, listed as CI 15510 in Annex IV of the EU Cosmetic Directive. The content of Acid Orange 7 in the test materials has not been measured using a standard reference material. The colour content (measured as HPLC peak area?) of various batches, reported in","page":25,"pdf":"sccs_o_057.pdf","row_type":"noael_study","study_id":"sccs_o_057_noael_005"} |
| SCCS_vision_codex | NOAEL | =2.5 | mg/kg bw/d | rat | oral | 13-weeks | NOAEL study | {"dose":"The NOAEL of a 13-weeks oral toxicity study in rats, was set to 2.5 mg/kg bw/d by the study authors.","effect":"reference material. The colour content (measured as HPLC peak area?) of various batches, reported in the table above, may not represent Acid Orange 7 content. Purity and impurities of all batches is not documented. Colour content in one of the batches is only 91%, but impurities in this batch are not reported. The stability in of Acid Orange 7 in typical hair dye formulations is not reported. The stability in an oxidative environment has not been demonstrated. Toxicity Acid Orange 7 is of low acute toxicity. The NOAEL of a 13-weeks oral toxicity study in rats, was set to 2.5 mg/kg bw/d by the study authors. It should be noted that at this dose, some slight early haematological effects (increased met-haemoglobin levels in males and increased reticulocytes count) are already observed. Even if they are in the upper limits of the historical control values, this finding could be test article related. Therefore the dose of 2.5 mg/kg bw/d should be considered as a LOAEL. Studies of effects on embryo-foetal development lead to a NOAEL","page":25,"pdf":"sccs_o_057.pdf","row_type":"noael_study","study_id":"sccs_o_057_noael_006"} |
| SCCS_vision_codex | NOAEL | =5 | mg/kg bw/d | rat | oral | 13-weeks | dermal absorption | {"dose":"NOAEL of a 13-weeks oral toxicity study in rats, was set to 2.5 mg/kg bw/d by the study authors.","effect":"NOAEL of a 13-weeks oral toxicity study in rats, was set to 2.5 mg/kg bw/d by the study authors. It should be noted that at this dose, some slight early haematological effects (increased met-haemoglobin levels in males and increased reticulocytes count) are already observed. Even if they are in the upper limits of the historical control values, this finding could be test article related. Therefore the dose of 2.5 mg/kg bw/d should be considered as a LOAEL. Studies of effects on embryo-foetal development lead to a NOAEL of 5 mg/kg bw/d for maternal toxicity and 320 mg/kg bw/d for foetal toxicity. Irritation and sensitization The assessment of skin and eye irritation does not complying with the current standards; nevertheless, there is no reason to ask for a repetition of these studies. According to the studies available, Acid Orange 7 is not irritating to rabbit skin and not a sensitiser. Percutaneous absorption Under the reported conditions, the dermal absorption of Acid Orange 7 is 1.13 ± 1.15 µg/cm² or 1.25 ± 1.20% (mean v","page":25,"pdf":"sccs_o_057.pdf","row_type":"noael_study","study_id":"sccs_o_057_noael_007"} |
| SCCS_vision_codex | NOAEL | =2.5 | mg/kg bw/day | - | - | - | NOAEL study | {"citation":"Ref.: 14 Comment It should be noted that at this dose, some slight early haematological effects (increased met-haemoglobin levels in males and increased reticulocytes count) are already","dose":"hological (extramedullary hemopoiesis in the spleen) or other haematological parameters at 2.5 mg/kg bw/day.","effect":"hological (extramedullary hemopoiesis in the spleen) or other haematological parameters at 2.5 mg/kg bw/day. In males treated with 10 mg/kg bw/day, increased organ/body weight ratio in the spleen was noted, which correlated to microscopic findings (extramedullary hemopoiesis in the spleen in all animals treated with 5-10 mg/kg bw/day. No test article related macroscopic findings were observed during necropsy. With regard to the results obtained this, especially to changes in haematological parameters of males, the No Observed Adverse Effect Level (NOAEL) of Acid Orange 7 was considered to be in the general range around 2.5 mg/kg bw/day. This dose led to borderline effects on met-hemoglobin and reticulocytes counts without concurrent effects on the spleen. The NOAEL for females was set to 2.5 mg/kg bw/ day by the study authors. Ref.: 14 Comment It should be noted that at this dose, some slight early haematological effects (increased met-haemoglobin levels in males and increased reticulocytes count) are already observed. Even if there are in the upper limit","page":18,"pdf":"sccs_o_057.pdf","row_type":"noael_study","study_id":"sccs_o_057_noael_001"} |
| SCCS_vision_codex | NOAEL | =2.5 | mg/kg bw/ day | rabbit | dermal | - | NOAEL study | {"citation":"Ref.: 14 Comment It should be noted that at this dose, some slight early haematological effects (increased met-haemoglobin levels in males and increased reticulocytes count) are already","dose":"xtramedullary hemopoiesis in the spleen in all animals treated with 5-10 mg/kg bw/day.","effect":"xtramedullary hemopoiesis in the spleen in all animals treated with 5-10 mg/kg bw/day. No test article related macroscopic findings were observed during necropsy. With regard to the results obtained this, especially to changes in haematological parameters of males, the No Observed Adverse Effect Level (NOAEL) of Acid Orange 7 was considered to be in the general range around 2.5 mg/kg bw/day. This dose led to borderline effects on met-hemoglobin and reticulocytes counts without concurrent effects on the spleen. The NOAEL for females was set to 2.5 mg/kg bw/ day by the study authors. Ref.: 14 Comment It should be noted that at this dose, some slight early haematological effects (increased met-haemoglobin levels in males and increased reticulocytes count) are already observed. Even if there are in the upper limits of the historical control values, this finding could be test article related. Therefore, the dose of 2.5 mg/kg bw /day is considered as the LOAEL. 90–day dermal toxicity 3 animals each group (rabbits) were used for thi","page":18,"pdf":"sccs_o_057.pdf","row_type":"noael_study","study_id":"sccs_o_057_noael_003"} |
| SCCS_vision_codex | NOAEL | =5 | mg/kg bw/day | human | - | - | NOAEL study | {"citation":"Ref.: 19 3","dose":"Total resorptions were observed in 2 females in the high dose group.","effect":"consumption was also observed. Total resorptions were observed in 2 females in the high dose group. In the females treated at the dose of 40 and 320 mg/kg bw/day, a significant dose-related increased spleen weights was observed. Foetal toxicity: No abnormalities related to the treatment were observed in any foetuses. In the foetuses of group treated at 1000 mg/kg bw/day (dose not used), a slight decrease in the mean body weight was observed. Conclusion Based on the result, the No-Observable-Adverse-Effect-Level (NOAEL) of Acid Orange 7 was considered to be 5 mg/kg bw/day for the maternal organism and 320 mg/kg bw/day for the foetal organism. Ref.: 19 3.3.9. Toxicokinetics No data submitted 3.3.10. Photo-induced toxicity 3.3.10.1. Phototoxicity / photoirritation and photosensitisation No data submitted 3.3.10.2. Phototoxicity / photomutagenicity / photoclastogenicity No data submitted 3.3.11. Human data No data submitted 3.3.12. Special investigations No data submitted","page":24,"pdf":"sccs_o_057.pdf","row_type":"noael_study","study_id":"sccs_o_057_noael_004"} |
| SCCS_vision_codex | NOAEL | =0.83 | mg/kg bw/d | rat | oral | 13-week | dermal absorption | {"dose":"Safety evaluation (including calculation of the MoS) CALCULATION OF THE MARGIN OF SAFETY Acid Orange 7 (non-oxidative conditions) Absorption through the skin A (mean + 2SD) = 3.43 µg/cm² Skin Area surface SAS = 580 cm2 Dermal absorption per treatment SAS x A x 0.001 = 1.99 mg Typical body weight of human = 60 kg Systemic exposure dose (SED) SAS...","effect":"25 3.3.13. Safety evaluation (including calculation of the MoS) CALCULATION OF THE MARGIN OF SAFETY Acid Orange 7 (non-oxidative conditions) Absorption through the skin A (mean + 2SD) = 3.43 µg/cm² Skin Area surface SAS = 580 cm2 Dermal absorption per treatment SAS x A x 0.001 = 1.99 mg Typical body weight of human = 60 kg Systemic exposure dose (SED) SAS x A x 0.001/60 = 0.033 mg/kg bw Lowest Observed Adverse Effect Level LOAEL = 2.5 mg/kg bw/d (13-week, oral, rat) Adjusted by factor 3 = 0.83 mg/kg bw/d MOS NOAEL / SED = 25 3.3.14. Discussion Physico-chemical properties Acid Orange 7 is intended for use in oxidative and non-oxidative hair dye formulations as a direct dye at a maximum concentration of 0.5%. Acid Orange 7 is also permitted to be used as a cosmetic colorant, listed as CI 15510 in Annex IV of the EU Cosmetic Directive. The content of Acid Orange 7 in the test materials has not been measured using a standard reference material. The colour content (measured as HPLC peak area?) of various batches, reported in","page":25,"pdf":"sccs_o_057.pdf","row_type":"noael_study","study_id":"sccs_o_057_noael_005"} |
| SCCS_vision_codex | NOAEL | =2.5 | mg/kg bw/d | rat | oral | 13-weeks | NOAEL study | {"dose":"The NOAEL of a 13-weeks oral toxicity study in rats, was set to 2.5 mg/kg bw/d by the study authors.","effect":"reference material. The colour content (measured as HPLC peak area?) of various batches, reported in the table above, may not represent Acid Orange 7 content. Purity and impurities of all batches is not documented. Colour content in one of the batches is only 91%, but impurities in this batch are not reported. The stability in of Acid Orange 7 in typical hair dye formulations is not reported. The stability in an oxidative environment has not been demonstrated. Toxicity Acid Orange 7 is of low acute toxicity. The NOAEL of a 13-weeks oral toxicity study in rats, was set to 2.5 mg/kg bw/d by the study authors. It should be noted that at this dose, some slight early haematological effects (increased met-haemoglobin levels in males and increased reticulocytes count) are already observed. Even if they are in the upper limits of the historical control values, this finding could be test article related. Therefore the dose of 2.5 mg/kg bw/d should be considered as a LOAEL. Studies of effects on embryo-foetal development lead to a NOAEL","page":25,"pdf":"sccs_o_057.pdf","row_type":"noael_study","study_id":"sccs_o_057_noael_006"} |
| SCCS_vision_codex | NOAEL | =5 | mg/kg bw/d | rat | oral | 13-weeks | dermal absorption | {"dose":"NOAEL of a 13-weeks oral toxicity study in rats, was set to 2.5 mg/kg bw/d by the study authors.","effect":"NOAEL of a 13-weeks oral toxicity study in rats, was set to 2.5 mg/kg bw/d by the study authors. It should be noted that at this dose, some slight early haematological effects (increased met-haemoglobin levels in males and increased reticulocytes count) are already observed. Even if they are in the upper limits of the historical control values, this finding could be test article related. Therefore the dose of 2.5 mg/kg bw/d should be considered as a LOAEL. Studies of effects on embryo-foetal development lead to a NOAEL of 5 mg/kg bw/d for maternal toxicity and 320 mg/kg bw/d for foetal toxicity. Irritation and sensitization The assessment of skin and eye irritation does not complying with the current standards; nevertheless, there is no reason to ask for a repetition of these studies. According to the studies available, Acid Orange 7 is not irritating to rabbit skin and not a sensitiser. Percutaneous absorption Under the reported conditions, the dermal absorption of Acid Orange 7 is 1.13 ± 1.15 µg/cm² or 1.25 ± 1.20% (mean v","page":25,"pdf":"sccs_o_057.pdf","row_type":"noael_study","study_id":"sccs_o_057_noael_007"} |
| SCCS_vision_codex | NOAEL | =2.5 | mg/kg bw/day | - | - | - | NOAEL study | {"citation":"Ref.: 14 SCCS comment It should be noted that at this dose, some slight early haematological effects (increased met-haemoglobin levels in males and increased reticulocytes count) have be","dose":"ramedullary hemopoiesis in the spleen) or other haematological parameters at 2.5 mg/kg bw/day.","effect":"ramedullary hemopoiesis in the spleen) or other haematological parameters at 2.5 mg/kg bw/day. In males treated with 10 mg/kg bw/day, increased organ/body weight ratio in the spleen was noted, which correlated to microscopic findings (extramedullary hemopoiesis) in the spleen in all animals treated with 5-10 mg/kg bw/day. No test article-related macroscopic findings were observed during necropsy. With regard to the results obtained in this study, especially to changes in the haematological parameters of males, the No Observed Adverse Effect Level (NOAEL) of Acid Orange 7 was considered to be in the general range of around 2.5 mg/kg bw/day. This dose led to borderline effects on met-hemoglobin and reticulocytes counts without concurrent effects on the spleen. Conclusion The NOAEL for females was set to 2.5 mg/kg bw/ day by the study authors. Ref.: 14 SCCS comment It should be noted that at this dose, some slight early haematological effects (increased met-haemoglobin levels in males and increased reticulocytes count) have been observed. Even if they are","page":21,"pdf":"sccs_o_158.pdf","row_type":"noael_study","study_id":"sccs_o_158_noael_001"} |
| SCCS_vision_codex | NOAEL | =2.5 | mg/kg bw/ day | rabbit | dermal | - | NOAEL study | {"citation":"Ref.: 14 SCCS comment It should be noted that at this dose, some slight early haematological effects (increased met-haemoglobin levels in males and increased reticulocytes count) have be","dose":"the spleen in all animals treated with 5-10 mg/kg bw/day.","effect":"the spleen in all animals treated with 5-10 mg/kg bw/day. No test article-related macroscopic findings were observed during necropsy. With regard to the results obtained in this study, especially to changes in the haematological parameters of males, the No Observed Adverse Effect Level (NOAEL) of Acid Orange 7 was considered to be in the general range of around 2.5 mg/kg bw/day. This dose led to borderline effects on met-hemoglobin and reticulocytes counts without concurrent effects on the spleen. Conclusion The NOAEL for females was set to 2.5 mg/kg bw/ day by the study authors. Ref.: 14 SCCS comment It should be noted that at this dose, some slight early haematological effects (increased met-haemoglobin levels in males and increased reticulocytes count) have been observed. Even if they are in the upper limits of the historical control values, this finding could be test article related. Therefore, the dose of 2.5 mg/kg bw /day is considered as the LOAEL. 90–day dermal toxicity 3 animals per group (rabbits) were used for t","page":21,"pdf":"sccs_o_158.pdf","row_type":"noael_study","study_id":"sccs_o_158_noael_003"} |
| SCCS_vision_codex | NOAEL | =5 | mg/kg bw/day | human | - | - | NOAEL study | {"citation":"Ref.: 19 3","dose":"Total resorptions were observed in 2 females in the high dose group.","effect":"umption was also observed. Total resorptions were observed in 2 females in the high dose group. In the females treated at the dose of 40 and 320 mg/kg bw/day, a significant dose-related increased spleen weights was observed. Foetal toxicity: No abnormalities related to the treatment were observed in any foetuses. In the foetuses of the group treated at 1000 mg/kg bw/day (dose not used), a slight decrease in the mean body weight was observed. Conclusion Based on the result, the No-Observable-Adverse-Effect-Level (NOAEL) of Acid Orange 7 was considered to be 5 mg/kg bw/day for the maternal organism and 320 mg/kg bw/day for the foetal organism. Ref.: 19 3.3.9. Toxicokinetics No data submitted 3.3.10. Photo-induced toxicity 3.3.10.1. Phototoxicity / photoirritation and photosensitisation No data submitted 3.3.10.2. Phototoxicity / photomutagenicity / photoclastogenicity No data submitted 3.3.11. Human data No data submitted 3.3.12. Special investigations No data submitted","page":27,"pdf":"sccs_o_158.pdf","row_type":"noael_study","study_id":"sccs_o_158_noael_004"} |
| SCCS_vision_codex | NOAEL | =50 | % | rat | oral | 13-week | dermal absorption | {"dose":"ncluding calculation of the MoS) CALCULATION OF THE MARGIN OF SAFETY Acid Orange 7 (non-oxidative conditions) Absorption through the skin A (mean + 1 SD) = 0.25 µg/cm² Skin Area surface SAS = 580 cm2 Dermal absorption per treatment SAS x A x 0.001 = 0.145 mg Typical body weight of human = 60 kg Systemic exposure dose (SED) SAS x A x 0.001/60 = 0...","effect":"ncluding calculation of the MoS) CALCULATION OF THE MARGIN OF SAFETY Acid Orange 7 (non-oxidative conditions) Absorption through the skin A (mean + 1 SD) = 0.25 µg/cm² Skin Area surface SAS = 580 cm2 Dermal absorption per treatment SAS x A x 0.001 = 0.145 mg Typical body weight of human = 60 kg Systemic exposure dose (SED) SAS x A x 0.001/60 = 0.0024 mg/kg bw Lowest Observed Adverse Effect Level LOAEL = 2.5 mg/kg bw/d (13-week, oral, rat) Adjusted by factor 3 = 0.83 mg/kg bw/d Bioavailability 50% = 0.415 MoS NOAEL / SED = 172 3.3.14. Discussion Physico-chemical properties Acid Orange 7 is intended for use in oxidative and non-oxidative hair dye formulations as a direct dye at a maximum concentration of 0.5%. Acid Orange 7 is also permitted to be used as a cosmetic colorant, listed as CI 15510 in Annex IV of the EU Cosmetic Directive. The reported Acid Orange 7 content in various batches of test material should be considered semi-quantitative determination, because the content is determined only in terms of colour content","page":28,"pdf":"sccs_o_158.pdf","row_type":"noael_study","study_id":"sccs_o_158_noael_005"} |
| SCCS_vision_codex | NOAEL | =2.5 | mg/kg bw/d | rat | oral | 13-week | NOAEL study | {"dose":"The NOAEL of a 13-week oral toxicity study in rats was set to 2.5 mg/kg bw/d by the study authors.","effect":"ion, because the content is determined only in terms of colour content. Thus, impurities with the same colour (chromophore groups) will also be measured together with the active substance. Impurities in one of the batches of Acid Orange 7 (colour content 91%) were not reported. Stability of Acid Orange 7 under oxidative conditions of use has not been reported. In addition, the stability in of Acid Orange 7 in typical hair dye formulations is not reported. Toxicity Acid Orange 7 is of low acute oral toxicity. The NOAEL of a 13-week oral toxicity study in rats was set to 2.5 mg/kg bw/d by the study authors. It should be noted that at this dose, some slight early haematological effects (increased met-haemoglobin levels in males and increased reticulocytes count) have already been observed. Even if these are in the upper limits of the historical control values, this finding could be test article-related. Therefore the dose of 2.5 mg/kg bw/d should be considered as a LOAEL. Studies of effects on embryo-foetal development lead to a N","page":28,"pdf":"sccs_o_158.pdf","row_type":"noael_study","study_id":"sccs_o_158_noael_006"} |
| SCCS_vision_codex | NOAEL | =5 | mg/kg bw/d | rat | oral | 13-week | dermal absorption | {"dose":"L of a 13-week oral toxicity study in rats was set to 2.5 mg/kg bw/d by the study authors.","effect":"L of a 13-week oral toxicity study in rats was set to 2.5 mg/kg bw/d by the study authors. It should be noted that at this dose, some slight early haematological effects (increased met-haemoglobin levels in males and increased reticulocytes count) have already been observed. Even if these are in the upper limits of the historical control values, this finding could be test article-related. Therefore the dose of 2.5 mg/kg bw/d should be considered as a LOAEL. Studies of effects on embryo-foetal development lead to a NOAEL of 5 mg/kg bw/d for maternal toxicity and 320 mg/kg bw/d for foetal toxicity. Irritation and sensitisation The assessment of skin and eye irritation does not comply with the current standards. According to the studies available, Acid Orange 7 is considered a mild skin irritant. Based on the data submitted, eye irritation potential cannot be evaluated. Based on the result in the available studies, Acid Orange 7 is not a skin sensitiser. Percutaneous absorption For the calculation of MoS, the mean+ 1 SD dermal ab","page":28,"pdf":"sccs_o_158.pdf","row_type":"noael_study","study_id":"sccs_o_158_noael_007"} |
| SCCS_vision_codex | NOAEL | =2.5 | mg/kg bw/day | - | - | - | NOAEL study | {"citation":"Ref.: 14 SCCS comment It should be noted that at this dose, some slight early haematological effects (increased met-haemoglobin levels in males and increased reticulocytes count) have be","dose":"ramedullary hemopoiesis in the spleen) or other haematological parameters at 2.5 mg/kg bw/day.","effect":"ramedullary hemopoiesis in the spleen) or other haematological parameters at 2.5 mg/kg bw/day. In males treated with 10 mg/kg bw/day, increased organ/body weight ratio in the spleen was noted, which correlated to microscopic findings (extramedullary hemopoiesis) in the spleen in all animals treated with 5-10 mg/kg bw/day. No test article-related macroscopic findings were observed during necropsy. With regard to the results obtained in this study, especially to changes in the haematological parameters of males, the No Observed Adverse Effect Level (NOAEL) of Acid Orange 7 was considered to be in the general range of around 2.5 mg/kg bw/day. This dose led to borderline effects on met-hemoglobin and reticulocytes counts without concurrent effects on the spleen. Conclusion The NOAEL for females was set to 2.5 mg/kg bw/ day by the study authors. Ref.: 14 SCCS comment It should be noted that at this dose, some slight early haematological effects (increased met-haemoglobin levels in males and increased reticulocytes count) have been observed. Even if they are","page":21,"pdf":"sccs_o_158.pdf","row_type":"noael_study","study_id":"sccs_o_158_noael_001"} |
| SCCS_vision_codex | NOAEL | =2.5 | mg/kg bw/ day | rabbit | dermal | - | NOAEL study | {"citation":"Ref.: 14 SCCS comment It should be noted that at this dose, some slight early haematological effects (increased met-haemoglobin levels in males and increased reticulocytes count) have be","dose":"the spleen in all animals treated with 5-10 mg/kg bw/day.","effect":"the spleen in all animals treated with 5-10 mg/kg bw/day. No test article-related macroscopic findings were observed during necropsy. With regard to the results obtained in this study, especially to changes in the haematological parameters of males, the No Observed Adverse Effect Level (NOAEL) of Acid Orange 7 was considered to be in the general range of around 2.5 mg/kg bw/day. This dose led to borderline effects on met-hemoglobin and reticulocytes counts without concurrent effects on the spleen. Conclusion The NOAEL for females was set to 2.5 mg/kg bw/ day by the study authors. Ref.: 14 SCCS comment It should be noted that at this dose, some slight early haematological effects (increased met-haemoglobin levels in males and increased reticulocytes count) have been observed. Even if they are in the upper limits of the historical control values, this finding could be test article related. Therefore, the dose of 2.5 mg/kg bw /day is considered as the LOAEL. 90–day dermal toxicity 3 animals per group (rabbits) were used for t","page":21,"pdf":"sccs_o_158.pdf","row_type":"noael_study","study_id":"sccs_o_158_noael_003"} |
| SCCS_vision_codex | NOAEL | =5 | mg/kg bw/day | human | - | - | NOAEL study | {"citation":"Ref.: 19 3","dose":"Total resorptions were observed in 2 females in the high dose group.","effect":"umption was also observed. Total resorptions were observed in 2 females in the high dose group. In the females treated at the dose of 40 and 320 mg/kg bw/day, a significant dose-related increased spleen weights was observed. Foetal toxicity: No abnormalities related to the treatment were observed in any foetuses. In the foetuses of the group treated at 1000 mg/kg bw/day (dose not used), a slight decrease in the mean body weight was observed. Conclusion Based on the result, the No-Observable-Adverse-Effect-Level (NOAEL) of Acid Orange 7 was considered to be 5 mg/kg bw/day for the maternal organism and 320 mg/kg bw/day for the foetal organism. Ref.: 19 3.3.9. Toxicokinetics No data submitted 3.3.10. Photo-induced toxicity 3.3.10.1. Phototoxicity / photoirritation and photosensitisation No data submitted 3.3.10.2. Phototoxicity / photomutagenicity / photoclastogenicity No data submitted 3.3.11. Human data No data submitted 3.3.12. Special investigations No data submitted","page":27,"pdf":"sccs_o_158.pdf","row_type":"noael_study","study_id":"sccs_o_158_noael_004"} |
| SCCS_vision_codex | NOAEL | =50 | % | rat | oral | 13-week | dermal absorption | {"dose":"ncluding calculation of the MoS) CALCULATION OF THE MARGIN OF SAFETY Acid Orange 7 (non-oxidative conditions) Absorption through the skin A (mean + 1 SD) = 0.25 µg/cm² Skin Area surface SAS = 580 cm2 Dermal absorption per treatment SAS x A x 0.001 = 0.145 mg Typical body weight of human = 60 kg Systemic exposure dose (SED) SAS x A x 0.001/60 = 0...","effect":"ncluding calculation of the MoS) CALCULATION OF THE MARGIN OF SAFETY Acid Orange 7 (non-oxidative conditions) Absorption through the skin A (mean + 1 SD) = 0.25 µg/cm² Skin Area surface SAS = 580 cm2 Dermal absorption per treatment SAS x A x 0.001 = 0.145 mg Typical body weight of human = 60 kg Systemic exposure dose (SED) SAS x A x 0.001/60 = 0.0024 mg/kg bw Lowest Observed Adverse Effect Level LOAEL = 2.5 mg/kg bw/d (13-week, oral, rat) Adjusted by factor 3 = 0.83 mg/kg bw/d Bioavailability 50% = 0.415 MoS NOAEL / SED = 172 3.3.14. Discussion Physico-chemical properties Acid Orange 7 is intended for use in oxidative and non-oxidative hair dye formulations as a direct dye at a maximum concentration of 0.5%. Acid Orange 7 is also permitted to be used as a cosmetic colorant, listed as CI 15510 in Annex IV of the EU Cosmetic Directive. The reported Acid Orange 7 content in various batches of test material should be considered semi-quantitative determination, because the content is determined only in terms of colour content","page":28,"pdf":"sccs_o_158.pdf","row_type":"noael_study","study_id":"sccs_o_158_noael_005"} |
| SCCS_vision_codex | NOAEL | =2.5 | mg/kg bw/d | rat | oral | 13-week | NOAEL study | {"dose":"The NOAEL of a 13-week oral toxicity study in rats was set to 2.5 mg/kg bw/d by the study authors.","effect":"ion, because the content is determined only in terms of colour content. Thus, impurities with the same colour (chromophore groups) will also be measured together with the active substance. Impurities in one of the batches of Acid Orange 7 (colour content 91%) were not reported. Stability of Acid Orange 7 under oxidative conditions of use has not been reported. In addition, the stability in of Acid Orange 7 in typical hair dye formulations is not reported. Toxicity Acid Orange 7 is of low acute oral toxicity. The NOAEL of a 13-week oral toxicity study in rats was set to 2.5 mg/kg bw/d by the study authors. It should be noted that at this dose, some slight early haematological effects (increased met-haemoglobin levels in males and increased reticulocytes count) have already been observed. Even if these are in the upper limits of the historical control values, this finding could be test article-related. Therefore the dose of 2.5 mg/kg bw/d should be considered as a LOAEL. Studies of effects on embryo-foetal development lead to a N","page":28,"pdf":"sccs_o_158.pdf","row_type":"noael_study","study_id":"sccs_o_158_noael_006"} |
| SCCS_vision_codex | NOAEL | =5 | mg/kg bw/d | rat | oral | 13-week | dermal absorption | {"dose":"L of a 13-week oral toxicity study in rats was set to 2.5 mg/kg bw/d by the study authors.","effect":"L of a 13-week oral toxicity study in rats was set to 2.5 mg/kg bw/d by the study authors. It should be noted that at this dose, some slight early haematological effects (increased met-haemoglobin levels in males and increased reticulocytes count) have already been observed. Even if these are in the upper limits of the historical control values, this finding could be test article-related. Therefore the dose of 2.5 mg/kg bw/d should be considered as a LOAEL. Studies of effects on embryo-foetal development lead to a NOAEL of 5 mg/kg bw/d for maternal toxicity and 320 mg/kg bw/d for foetal toxicity. Irritation and sensitisation The assessment of skin and eye irritation does not comply with the current standards. According to the studies available, Acid Orange 7 is considered a mild skin irritant. Based on the data submitted, eye irritation potential cannot be evaluated. Based on the result in the available studies, Acid Orange 7 is not a skin sensitiser. Percutaneous absorption For the calculation of MoS, the mean+ 1 SD dermal ab","page":28,"pdf":"sccs_o_158.pdf","row_type":"noael_study","study_id":"sccs_o_158_noael_007"} |
| SCCS_vision_codex | NOAEL | =2.5 | mg/kg bw/day | - | - | - | NOAEL study | {"citation":"Ref.: 14 Comment It should be noted that at this dose, some slight early haematological effects (increased met-haemoglobin levels in males and increased reticulocytes count) are already","dose":"hological (extramedullary hemopoiesis in the spleen) or other haematological parameters at 2.5 mg/kg bw/day.","effect":"hological (extramedullary hemopoiesis in the spleen) or other haematological parameters at 2.5 mg/kg bw/day. In males treated with 10 mg/kg bw/day, increased organ/body weight ratio in the spleen was noted, which correlated to microscopic findings (extramedullary hemopoiesis in the spleen in all animals treated with 5-10 mg/kg bw/day. No test article related macroscopic findings were observed during necropsy. With regard to the results obtained this, especially to changes in haematological parameters of males, the No Observed Adverse Effect Level (NOAEL) of Acid Orange 7 was considered to be in the general range around 2.5 mg/kg bw/day. This dose led to borderline effects on met-hemoglobin and reticulocytes counts without concurrent effects on the spleen. The NOAEL for females was set to 2.5 mg/kg bw/ day by the study authors. Ref.: 14 Comment It should be noted that at this dose, some slight early haematological effects (increased met-haemoglobin levels in males and increased reticulocytes count) are already observed. Even if there are in the upper limit","page":18,"pdf":"sccs_o_057.pdf","row_type":"noael_study","study_id":"sccs_o_057_noael_001"} |
| SCCS_vision_codex | NOAEL | =2.5 | mg/kg bw/ day | rabbit | dermal | - | NOAEL study | {"citation":"Ref.: 14 Comment It should be noted that at this dose, some slight early haematological effects (increased met-haemoglobin levels in males and increased reticulocytes count) are already","dose":"xtramedullary hemopoiesis in the spleen in all animals treated with 5-10 mg/kg bw/day.","effect":"xtramedullary hemopoiesis in the spleen in all animals treated with 5-10 mg/kg bw/day. No test article related macroscopic findings were observed during necropsy. With regard to the results obtained this, especially to changes in haematological parameters of males, the No Observed Adverse Effect Level (NOAEL) of Acid Orange 7 was considered to be in the general range around 2.5 mg/kg bw/day. This dose led to borderline effects on met-hemoglobin and reticulocytes counts without concurrent effects on the spleen. The NOAEL for females was set to 2.5 mg/kg bw/ day by the study authors. Ref.: 14 Comment It should be noted that at this dose, some slight early haematological effects (increased met-haemoglobin levels in males and increased reticulocytes count) are already observed. Even if there are in the upper limits of the historical control values, this finding could be test article related. Therefore, the dose of 2.5 mg/kg bw /day is considered as the LOAEL. 90–day dermal toxicity 3 animals each group (rabbits) were used for thi","page":18,"pdf":"sccs_o_057.pdf","row_type":"noael_study","study_id":"sccs_o_057_noael_003"} |
| SCCS_vision_codex | NOAEL | =5 | mg/kg bw/day | human | - | - | NOAEL study | {"citation":"Ref.: 19 3","dose":"Total resorptions were observed in 2 females in the high dose group.","effect":"consumption was also observed. Total resorptions were observed in 2 females in the high dose group. In the females treated at the dose of 40 and 320 mg/kg bw/day, a significant dose-related increased spleen weights was observed. Foetal toxicity: No abnormalities related to the treatment were observed in any foetuses. In the foetuses of group treated at 1000 mg/kg bw/day (dose not used), a slight decrease in the mean body weight was observed. Conclusion Based on the result, the No-Observable-Adverse-Effect-Level (NOAEL) of Acid Orange 7 was considered to be 5 mg/kg bw/day for the maternal organism and 320 mg/kg bw/day for the foetal organism. Ref.: 19 3.3.9. Toxicokinetics No data submitted 3.3.10. Photo-induced toxicity 3.3.10.1. Phototoxicity / photoirritation and photosensitisation No data submitted 3.3.10.2. Phototoxicity / photomutagenicity / photoclastogenicity No data submitted 3.3.11. Human data No data submitted 3.3.12. Special investigations No data submitted","page":24,"pdf":"sccs_o_057.pdf","row_type":"noael_study","study_id":"sccs_o_057_noael_004"} |
| SCCS_vision_codex | NOAEL | =0.83 | mg/kg bw/d | rat | oral | 13-week | dermal absorption | {"dose":"Safety evaluation (including calculation of the MoS) CALCULATION OF THE MARGIN OF SAFETY Acid Orange 7 (non-oxidative conditions) Absorption through the skin A (mean + 2SD) = 3.43 µg/cm² Skin Area surface SAS = 580 cm2 Dermal absorption per treatment SAS x A x 0.001 = 1.99 mg Typical body weight of human = 60 kg Systemic exposure dose (SED) SAS...","effect":"25 3.3.13. Safety evaluation (including calculation of the MoS) CALCULATION OF THE MARGIN OF SAFETY Acid Orange 7 (non-oxidative conditions) Absorption through the skin A (mean + 2SD) = 3.43 µg/cm² Skin Area surface SAS = 580 cm2 Dermal absorption per treatment SAS x A x 0.001 = 1.99 mg Typical body weight of human = 60 kg Systemic exposure dose (SED) SAS x A x 0.001/60 = 0.033 mg/kg bw Lowest Observed Adverse Effect Level LOAEL = 2.5 mg/kg bw/d (13-week, oral, rat) Adjusted by factor 3 = 0.83 mg/kg bw/d MOS NOAEL / SED = 25 3.3.14. Discussion Physico-chemical properties Acid Orange 7 is intended for use in oxidative and non-oxidative hair dye formulations as a direct dye at a maximum concentration of 0.5%. Acid Orange 7 is also permitted to be used as a cosmetic colorant, listed as CI 15510 in Annex IV of the EU Cosmetic Directive. The content of Acid Orange 7 in the test materials has not been measured using a standard reference material. The colour content (measured as HPLC peak area?) of various batches, reported in","page":25,"pdf":"sccs_o_057.pdf","row_type":"noael_study","study_id":"sccs_o_057_noael_005"} |
| SCCS_vision_codex | NOAEL | =2.5 | mg/kg bw/d | rat | oral | 13-weeks | NOAEL study | {"dose":"The NOAEL of a 13-weeks oral toxicity study in rats, was set to 2.5 mg/kg bw/d by the study authors.","effect":"reference material. The colour content (measured as HPLC peak area?) of various batches, reported in the table above, may not represent Acid Orange 7 content. Purity and impurities of all batches is not documented. Colour content in one of the batches is only 91%, but impurities in this batch are not reported. The stability in of Acid Orange 7 in typical hair dye formulations is not reported. The stability in an oxidative environment has not been demonstrated. Toxicity Acid Orange 7 is of low acute toxicity. The NOAEL of a 13-weeks oral toxicity study in rats, was set to 2.5 mg/kg bw/d by the study authors. It should be noted that at this dose, some slight early haematological effects (increased met-haemoglobin levels in males and increased reticulocytes count) are already observed. Even if they are in the upper limits of the historical control values, this finding could be test article related. Therefore the dose of 2.5 mg/kg bw/d should be considered as a LOAEL. Studies of effects on embryo-foetal development lead to a NOAEL","page":25,"pdf":"sccs_o_057.pdf","row_type":"noael_study","study_id":"sccs_o_057_noael_006"} |
| SCCS_vision_codex | NOAEL | =5 | mg/kg bw/d | rat | oral | 13-weeks | dermal absorption | {"dose":"NOAEL of a 13-weeks oral toxicity study in rats, was set to 2.5 mg/kg bw/d by the study authors.","effect":"NOAEL of a 13-weeks oral toxicity study in rats, was set to 2.5 mg/kg bw/d by the study authors. It should be noted that at this dose, some slight early haematological effects (increased met-haemoglobin levels in males and increased reticulocytes count) are already observed. Even if they are in the upper limits of the historical control values, this finding could be test article related. Therefore the dose of 2.5 mg/kg bw/d should be considered as a LOAEL. Studies of effects on embryo-foetal development lead to a NOAEL of 5 mg/kg bw/d for maternal toxicity and 320 mg/kg bw/d for foetal toxicity. Irritation and sensitization The assessment of skin and eye irritation does not complying with the current standards; nevertheless, there is no reason to ask for a repetition of these studies. According to the studies available, Acid Orange 7 is not irritating to rabbit skin and not a sensitiser. Percutaneous absorption Under the reported conditions, the dermal absorption of Acid Orange 7 is 1.13 ± 1.15 µg/cm² or 1.25 ± 1.20% (mean v","page":25,"pdf":"sccs_o_057.pdf","row_type":"noael_study","study_id":"sccs_o_057_noael_007"} |
| SCCS_vision_codex | NOAEL | =2.5 | mg/kg bw/day | - | - | - | NOAEL study | {"citation":"Ref.: 14 SCCS comment It should be noted that at this dose, some slight early haematological effects (increased met-haemoglobin levels in males and increased reticulocytes count) have be","dose":"ramedullary hemopoiesis in the spleen) or other haematological parameters at 2.5 mg/kg bw/day.","effect":"ramedullary hemopoiesis in the spleen) or other haematological parameters at 2.5 mg/kg bw/day. In males treated with 10 mg/kg bw/day, increased organ/body weight ratio in the spleen was noted, which correlated to microscopic findings (extramedullary hemopoiesis) in the spleen in all animals treated with 5-10 mg/kg bw/day. No test article-related macroscopic findings were observed during necropsy. With regard to the results obtained in this study, especially to changes in the haematological parameters of males, the No Observed Adverse Effect Level (NOAEL) of Acid Orange 7 was considered to be in the general range of around 2.5 mg/kg bw/day. This dose led to borderline effects on met-hemoglobin and reticulocytes counts without concurrent effects on the spleen. Conclusion The NOAEL for females was set to 2.5 mg/kg bw/ day by the study authors. Ref.: 14 SCCS comment It should be noted that at this dose, some slight early haematological effects (increased met-haemoglobin levels in males and increased reticulocytes count) have been observed. Even if they are","page":21,"pdf":"sccs_o_158.pdf","row_type":"noael_study","study_id":"sccs_o_158_noael_001"} |
| SCCS_vision_codex | NOAEL | =2.5 | mg/kg bw/ day | rabbit | dermal | - | NOAEL study | {"citation":"Ref.: 14 SCCS comment It should be noted that at this dose, some slight early haematological effects (increased met-haemoglobin levels in males and increased reticulocytes count) have be","dose":"the spleen in all animals treated with 5-10 mg/kg bw/day.","effect":"the spleen in all animals treated with 5-10 mg/kg bw/day. No test article-related macroscopic findings were observed during necropsy. With regard to the results obtained in this study, especially to changes in the haematological parameters of males, the No Observed Adverse Effect Level (NOAEL) of Acid Orange 7 was considered to be in the general range of around 2.5 mg/kg bw/day. This dose led to borderline effects on met-hemoglobin and reticulocytes counts without concurrent effects on the spleen. Conclusion The NOAEL for females was set to 2.5 mg/kg bw/ day by the study authors. Ref.: 14 SCCS comment It should be noted that at this dose, some slight early haematological effects (increased met-haemoglobin levels in males and increased reticulocytes count) have been observed. Even if they are in the upper limits of the historical control values, this finding could be test article related. Therefore, the dose of 2.5 mg/kg bw /day is considered as the LOAEL. 90–day dermal toxicity 3 animals per group (rabbits) were used for t","page":21,"pdf":"sccs_o_158.pdf","row_type":"noael_study","study_id":"sccs_o_158_noael_003"} |
| SCCS_vision_codex | NOAEL | =5 | mg/kg bw/day | human | - | - | NOAEL study | {"citation":"Ref.: 19 3","dose":"Total resorptions were observed in 2 females in the high dose group.","effect":"umption was also observed. Total resorptions were observed in 2 females in the high dose group. In the females treated at the dose of 40 and 320 mg/kg bw/day, a significant dose-related increased spleen weights was observed. Foetal toxicity: No abnormalities related to the treatment were observed in any foetuses. In the foetuses of the group treated at 1000 mg/kg bw/day (dose not used), a slight decrease in the mean body weight was observed. Conclusion Based on the result, the No-Observable-Adverse-Effect-Level (NOAEL) of Acid Orange 7 was considered to be 5 mg/kg bw/day for the maternal organism and 320 mg/kg bw/day for the foetal organism. Ref.: 19 3.3.9. Toxicokinetics No data submitted 3.3.10. Photo-induced toxicity 3.3.10.1. Phototoxicity / photoirritation and photosensitisation No data submitted 3.3.10.2. Phototoxicity / photomutagenicity / photoclastogenicity No data submitted 3.3.11. Human data No data submitted 3.3.12. Special investigations No data submitted","page":27,"pdf":"sccs_o_158.pdf","row_type":"noael_study","study_id":"sccs_o_158_noael_004"} |
| SCCS_vision_codex | NOAEL | =50 | % | rat | oral | 13-week | dermal absorption | {"dose":"ncluding calculation of the MoS) CALCULATION OF THE MARGIN OF SAFETY Acid Orange 7 (non-oxidative conditions) Absorption through the skin A (mean + 1 SD) = 0.25 µg/cm² Skin Area surface SAS = 580 cm2 Dermal absorption per treatment SAS x A x 0.001 = 0.145 mg Typical body weight of human = 60 kg Systemic exposure dose (SED) SAS x A x 0.001/60 = 0...","effect":"ncluding calculation of the MoS) CALCULATION OF THE MARGIN OF SAFETY Acid Orange 7 (non-oxidative conditions) Absorption through the skin A (mean + 1 SD) = 0.25 µg/cm² Skin Area surface SAS = 580 cm2 Dermal absorption per treatment SAS x A x 0.001 = 0.145 mg Typical body weight of human = 60 kg Systemic exposure dose (SED) SAS x A x 0.001/60 = 0.0024 mg/kg bw Lowest Observed Adverse Effect Level LOAEL = 2.5 mg/kg bw/d (13-week, oral, rat) Adjusted by factor 3 = 0.83 mg/kg bw/d Bioavailability 50% = 0.415 MoS NOAEL / SED = 172 3.3.14. Discussion Physico-chemical properties Acid Orange 7 is intended for use in oxidative and non-oxidative hair dye formulations as a direct dye at a maximum concentration of 0.5%. Acid Orange 7 is also permitted to be used as a cosmetic colorant, listed as CI 15510 in Annex IV of the EU Cosmetic Directive. The reported Acid Orange 7 content in various batches of test material should be considered semi-quantitative determination, because the content is determined only in terms of colour content","page":28,"pdf":"sccs_o_158.pdf","row_type":"noael_study","study_id":"sccs_o_158_noael_005"} |
| SCCS_vision_codex | NOAEL | =2.5 | mg/kg bw/d | rat | oral | 13-week | NOAEL study | {"dose":"The NOAEL of a 13-week oral toxicity study in rats was set to 2.5 mg/kg bw/d by the study authors.","effect":"ion, because the content is determined only in terms of colour content. Thus, impurities with the same colour (chromophore groups) will also be measured together with the active substance. Impurities in one of the batches of Acid Orange 7 (colour content 91%) were not reported. Stability of Acid Orange 7 under oxidative conditions of use has not been reported. In addition, the stability in of Acid Orange 7 in typical hair dye formulations is not reported. Toxicity Acid Orange 7 is of low acute oral toxicity. The NOAEL of a 13-week oral toxicity study in rats was set to 2.5 mg/kg bw/d by the study authors. It should be noted that at this dose, some slight early haematological effects (increased met-haemoglobin levels in males and increased reticulocytes count) have already been observed. Even if these are in the upper limits of the historical control values, this finding could be test article-related. Therefore the dose of 2.5 mg/kg bw/d should be considered as a LOAEL. Studies of effects on embryo-foetal development lead to a N","page":28,"pdf":"sccs_o_158.pdf","row_type":"noael_study","study_id":"sccs_o_158_noael_006"} |
| SCCS_vision_codex | NOAEL | =5 | mg/kg bw/d | rat | oral | 13-week | dermal absorption | {"dose":"L of a 13-week oral toxicity study in rats was set to 2.5 mg/kg bw/d by the study authors.","effect":"L of a 13-week oral toxicity study in rats was set to 2.5 mg/kg bw/d by the study authors. It should be noted that at this dose, some slight early haematological effects (increased met-haemoglobin levels in males and increased reticulocytes count) have already been observed. Even if these are in the upper limits of the historical control values, this finding could be test article-related. Therefore the dose of 2.5 mg/kg bw/d should be considered as a LOAEL. Studies of effects on embryo-foetal development lead to a NOAEL of 5 mg/kg bw/d for maternal toxicity and 320 mg/kg bw/d for foetal toxicity. Irritation and sensitisation The assessment of skin and eye irritation does not comply with the current standards. According to the studies available, Acid Orange 7 is considered a mild skin irritant. Based on the data submitted, eye irritation potential cannot be evaluated. Based on the result in the available studies, Acid Orange 7 is not a skin sensitiser. Percutaneous absorption For the calculation of MoS, the mean+ 1 SD dermal ab","page":28,"pdf":"sccs_o_158.pdf","row_type":"noael_study","study_id":"sccs_o_158_noael_007"} |
ToxValDB_ECHA_IUCLID 3 endpoints
| Source | Endpoint Type | Value | Unit | Species | Route | Duration | Study Type | Reference |
|---|---|---|---|---|---|---|---|---|
| ToxValDB_ECHA_IUCLID | LOAEL | =5 | mg/kg bw/day | Rat | oral | - | reproduction developmental | QUALITY=4 (not assignable); STORED_SOURCE_RECORD=https://clowder.edap-cluster.com/files/669eac26e4b0a7c65d1bd95d; RECORD_SOURCE_LEVEL=Extraction document; SOURCE_URL=https://echa.europa.eu/; SUBSOURCE_URL=https://echa.europa.eu/registration-dossier/-/registered-dossier/17285/7/9/3?documentUUID=040ee780-aff4-454e-862c-ec8bfce09ecf; YEAR=2005; ORIGINAL_YEAR=2005; TOXICOLOGICAL_EFFECT=maternal: mortality; TOXICOLOGICAL_EFFECT_CATEGORY=mortality/survival; STUDY_GROUP=ECHA IUCLID_dup_Developmental Toxicity Teratogenicity_15822587_15823625:F:-maternal; QC_CATEGORY=Programmatically extracted from structured data source; Source overall passed QC, but this record was not manually checked; QC_STATUS=not determined; SOURCE_HASH=ToxValhc_ed1046f0a98505f8ceabde0a6e0c4b41 |
| ToxValDB_ECHA_IUCLID | LOAEL | =100 | mg/kg bw/day | Rat | oral | - | reproduction developmental | QUALITY=4 (not assignable); STORED_SOURCE_RECORD=https://clowder.edap-cluster.com/files/669eac26e4b0a7c65d1bd963; RECORD_SOURCE_LEVEL=Extraction document; SOURCE_URL=https://echa.europa.eu/; SUBSOURCE_URL=https://echa.europa.eu/registration-dossier/-/registered-dossier/17285/7/9/3?documentUUID=040ee780-aff4-454e-862c-ec8bfce09ecf; YEAR=2005; ORIGINAL_YEAR=2005; TOXICOLOGICAL_EFFECT=maternal: clinical signs; TOXICOLOGICAL_EFFECT_CATEGORY=clinical signs; STUDY_GROUP=ECHA IUCLID_dup_Developmental Toxicity Teratogenicity_15822587_15823625:F:-maternal; QC_CATEGORY=Programmatically extracted from structured data source; Source overall passed QC, and this record was expert reviewed; QC_STATUS=pass; SOURCE_HASH=ToxValhc_dcbafb106d3582775019184ed544d2da |
| ToxValDB_ECHA_IUCLID | NOAEL | =1000 | mg/kg bw/day | Rat | oral | - | developmental | QUALITY=4 (not assignable); STORED_SOURCE_RECORD=https://clowder.edap-cluster.com/files/669eac26e4b0a7c65d1bd95d; RECORD_SOURCE_LEVEL=Extraction document; SOURCE_URL=https://echa.europa.eu/; SUBSOURCE_URL=https://echa.europa.eu/registration-dossier/-/registered-dossier/17285/7/9/3?documentUUID=040ee780-aff4-454e-862c-ec8bfce09ecf; YEAR=2005; ORIGINAL_YEAR=2005; STUDY_GROUP=ECHA IUCLID_dup_Developmental Toxicity Teratogenicity_15821263_15823411_15823655_15823732:-:-fetal; QC_CATEGORY=Programmatically extracted from structured data source; Source overall passed QC, but this record was not manually checked; QC_STATUS=not determined; SOURCE_HASH=ToxValhc_65f1b0be7aa4b35d068cf04db1572cd1 |
ToxValDB_GESTIS_DNEL 1 endpoint
| Source | Endpoint Type | Value | Unit | Species | Route | Duration | Study Type | Reference |
|---|---|---|---|---|---|---|---|---|
| ToxValDB_GESTIS_DNEL | DNEL systemic | =0.176 | mg/m3 | Human | inhalation | - | Toxicity Value | STORED_SOURCE_RECORD=https://clowder.edap-cluster.com/files/6543dd69e4b045b9ff7cd87e; RECORD_SOURCE_LEVEL=Extraction document; SOURCE_URL=https://www.dguv.de/ifa/gestis/gestis-dnel-liste/index-2.jsp; STUDY_GROUP=GESTIS DNEL:15633929:-:--; QC_CATEGORY=Programmatically extracted from structured data source; Source overall passed QC, but this record was not manually checked; QC_STATUS=not determined; SOURCE_HASH=ToxValhc_1091a27f6f83ca1c4031bd953d08b001 |
UnifiedCodex:SCCNFP:beta.noael_studies 5 endpoints
| Source | Endpoint Type | Value | Unit | Species | Route | Duration | Study Type | Reference |
|---|---|---|---|---|---|---|---|---|
| UnifiedCodex:SCCNFP:beta.noael_studies | - | 5 | mg/kg | rat | oral | 13-weeks | - | SOURCE_SUBDIR=out259_en; REPORT_TITLE=OPINION OF THE SCIENTIFIC COMMITTEE ON COSMETIC PRODUCTS AND NON-FOOD PRODUCTS INTENDED FOR CONSUMERS CONCERNING ACID ORANGE 7 COLIPA n° C15; OPINION_NUMBER=SCCNFP/0785/04; COMMITTEE=SCCNFP; REPORT_DATE=adopted by the SCCNFP on 23 April 2004; VALUE_TEXT=5; DOSE=The NOAEL, derived from a 13-weeks oral toxicity study in rats, is 2.5 mg/kg/bw.; EFFECT=ation system. Ref.: a, b Human studies No data 2.10. Special investigations No data 2.11. Safety evaluation Not applicable 2.12. Conclusions Physico-chemical properties Absolute content of Acid Orange 7 has not been reported for any batch of the test material. The stability in a prototype formulation is not reported. Toxicity Acid Orange 7 is of very low acute toxicity. The NOAEL, derived from a 13-weeks oral toxicity study in rats, is 2.5 mg/kg/bw. Studies of effects on embryo-foetal development lead to a NOAEL of 5 mg/kg/bw for the maternal organism and 320 mg/kg/bw for the foetal organism.; CITATION=Ref.: a, b Human studies No data 2; CITATION_NUMBERS=[2]; REFERENCE=Ref.: a, b Human studies No data 2; DETAILS_JSON={"cas_number":"633-96-5","citation":"Ref.: a, b Human studies No data 2","dose":"The NOAEL, derived from a 13-weeks oral toxicity study in rats, is 2.5 mg/kg/bw.","duration":"13-weeks","effect":"ation system. Ref.: a, b Human studies No data 2.10. Special investigations No data 2.11. Safety evaluation Not applicable 2.12. Conclusions Physico-chemical properties Absolute content of Acid Orange 7 has not been reported for any batch of the test material. The stability in a prototype formulation is not reported. Toxicity Acid Orange 7 is of very low acute toxicity. The NOAEL, derived from a 13-weeks oral toxicity study in rats, is 2.5 mg/kg/bw. Studies of effects on embryo-foetal development lead to a NOAEL of 5 mg/kg/bw for the maternal organism and 320 mg/kg/bw for the foetal organism.","endpoint":"","ingredient":"codes","loael_value":"","noael_unit":"mg/kg","noael_value":"5","page":18,"route":"oral","species":"rat","study_id":"out259_en_noael_005"} |
| UnifiedCodex:SCCNFP:beta.noael_studies | dermal absorption | 5 | mg/kg | rat | oral | - | dermal absorption | SOURCE_SUBDIR=out259_en; REPORT_TITLE=OPINION OF THE SCIENTIFIC COMMITTEE ON COSMETIC PRODUCTS AND NON-FOOD PRODUCTS INTENDED FOR CONSUMERS CONCERNING ACID ORANGE 7 COLIPA n° C15; OPINION_NUMBER=SCCNFP/0785/04; COMMITTEE=SCCNFP; REPORT_DATE=adopted by the SCCNFP on 23 April 2004; VALUE_TEXT=5; DOSE=0, 5, 40, 320 mg/kg bw/day.; EFFECT=r the study: 0, 5, 40, 320 mg/kg bw/day. The animals (22 mated female rats, each concentration) were treated by oral gavage, once daily from day 6 through to day 17 post coitum (last treatment). A standard dose volume of 10 ml/kg bw was used. Females were sacrificed on day 21 post coitum and the foetuses were removed after Caesarean section. The examination of the dams and foetuses was performed in accordance with international recommendations. Results Based on the result, the No-Observable-Adverse-Effect-Level (NOAEL) of Acid Orange 7 [D&C Orange 4 (C.I. 15510)] was considered to be 5 mg/kg body weight/day for the maternal organism and 320 mg/kg body weight for the foetal organism. Ref.: 19 2.7. Toxicokinetics (incl. Percutaneous Absorption) Percutaneous absorption study Guideline : OECD 428 (1999) Test system : pig ear skin (400-500 µm), 12 samples, skin integrity checked by conductivity measurement Contact time : 30 minutes then washing with a shampoo, diffusion monitored during 24 hours Test substance : D&C orang; CITATION=Ref.: 19 2; CITATION_NUMBERS=[19,2]; REFERENCE=Ref.: 19 2; DETAILS_JSON={"cas_number":"633-96-5","citation":"Ref.: 19 2","dose":"0, 5, 40, 320 mg/kg bw/day.","duration":"","effect":"r the study: 0, 5, 40, 320 mg/kg bw/day. The animals (22 mated female rats, each concentration) were treated by oral gavage, once daily from day 6 through to day 17 post coitum (last treatment). A standard dose volume of 10 ml/kg bw was used. Females were sacrificed on day 21 post coitum and the foetuses were removed after Caesarean section. The examination of the dams and foetuses was performed in accordance with international recommendations. Results Based on the result, the No-Observable-Adverse-Effect-Level (NOAEL) of Acid Orange 7 [D&C Orange 4 (C.I. 15510)] was considered to be 5 mg/kg body weight/day for the maternal organism and 320 mg/kg body weight for the foetal organism. Ref.: 19 2.7. Toxicokinetics (incl. Percutaneous Absorption) Percutaneous absorption study Guideline : OECD 428 (1999) Test system : pig ear skin (400-500 µm), 12 samples, skin integrity checked by conductivity measurement Contact time : 30 minutes then washing with a shampoo, diffusion monitored during 24 hours Test substance : D&C orang","endpoint":"dermal absorption","ingredient":"codes","loael_value":"","noael_unit":"mg/kg","noael_value":"5","page":13,"route":"oral","species":"rat","study_id":"out259_en_noael_003"} |
| UnifiedCodex:SCCNFP:beta.noael_studies | genotoxicity | 2.5 | mg/kg | rat | oral | 13-weeks | genotoxicity | SOURCE_SUBDIR=out259_en; REPORT_TITLE=OPINION OF THE SCIENTIFIC COMMITTEE ON COSMETIC PRODUCTS AND NON-FOOD PRODUCTS INTENDED FOR CONSUMERS CONCERNING ACID ORANGE 7 COLIPA n° C15; OPINION_NUMBER=SCCNFP/0785/04; COMMITTEE=SCCNFP; REPORT_DATE=adopted by the SCCNFP on 23 April 2004; VALUE_TEXT=2.5; DOSE=The NOAEL, derived from a 13-weeks oral toxicity study in rats, is 2.5 mg/kg/bw.; EFFECT=-Amino-2-naphthol hydrochloride showed no evidence of mutagenicity in Salmonella typhimurium bacteria with or without a rat liver activation system. Ref.: a, b Human studies No data 2.10. Special investigations No data 2.11. Safety evaluation Not applicable 2.12. Conclusions Physico-chemical properties Absolute content of Acid Orange 7 has not been reported for any batch of the test material. The stability in a prototype formulation is not reported. Toxicity Acid Orange 7 is of very low acute toxicity. The NOAEL, derived from a 13-weeks oral toxicity study in rats, is 2.5 mg/kg/bw. Studies of effects on embryo-foetal development lead to a NOAEL of 5 mg/kg/bw for the maternal organism and 320 mg/kg/bw for the foetal organism.; CITATION=Ref.: a, b Human studies No data 2; CITATION_NUMBERS=[2]; REFERENCE=Ref.: a, b Human studies No data 2; DETAILS_JSON={"cas_number":"633-96-5","citation":"Ref.: a, b Human studies No data 2","dose":"The NOAEL, derived from a 13-weeks oral toxicity study in rats, is 2.5 mg/kg/bw.","duration":"13-weeks","effect":"-Amino-2-naphthol hydrochloride showed no evidence of mutagenicity in Salmonella typhimurium bacteria with or without a rat liver activation system. Ref.: a, b Human studies No data 2.10. Special investigations No data 2.11. Safety evaluation Not applicable 2.12. Conclusions Physico-chemical properties Absolute content of Acid Orange 7 has not been reported for any batch of the test material. The stability in a prototype formulation is not reported. Toxicity Acid Orange 7 is of very low acute toxicity. The NOAEL, derived from a 13-weeks oral toxicity study in rats, is 2.5 mg/kg/bw. Studies of effects on embryo-foetal development lead to a NOAEL of 5 mg/kg/bw for the maternal organism and 320 mg/kg/bw for the foetal organism.","endpoint":"genotoxicity","ingredient":"codes","loael_value":"","noael_unit":"mg/kg","noael_value":"2.5","page":18,"route":"oral","species":"rat","study_id":"out259_en_noael_004"} |
| UnifiedCodex:SCCNFP:beta.noael_studies | repeated dose toxicity | 2.5 | mg/kg | rabbit | dermal | Sub-chronic | repeated dose toxicity | SOURCE_SUBDIR=out259_en; REPORT_TITLE=OPINION OF THE SCIENTIFIC COMMITTEE ON COSMETIC PRODUCTS AND NON-FOOD PRODUCTS INTENDED FOR CONSUMERS CONCERNING ACID ORANGE 7 COLIPA n° C15; OPINION_NUMBER=SCCNFP/0785/04; COMMITTEE=SCCNFP; REPORT_DATE=adopted by the SCCNFP on 23 April 2004; VALUE_TEXT=2.5; DOSE=emopoiesis in the spleen) or other haematological parameters at 2.5 mg/kg/day.; EFFECT=emopoiesis in the spleen) or other haematological parameters at 2.5 mg/kg/day. In males treated with 10 mg/kg/day, increased organ/body weight ratio in the spleen was noted, which correlated to microscopic findings (extramedullary hemopoiesis in the spleen in all animals treated with 5-10 mg/kg/day. No test article related macroscopic findings were observed during necropsy. With regard to the results obtained this, especially to changes in haematological parameters of males, the No-Observable-Adverse-Effect-Level (NOAEL) of Acid Orange 7 [D&C Orange 4 (C.I. 15510)] was considered to be in the general range around 2.5 mg/kg body weight/day. This dose led to borderline effects on met-hemoglobin and reticulocytes counts without concurrent effects on the spleen. The NOAEL for females could be set to 2.5 mg/kg/body weight/ day. Ref.: 14 2.3.8. Sub-chronic dermal toxicity 3 animals each group (rabbits) were used for this assay. The test material (FDA certified material) was applied to the depilated skin of rabbits. Daily application; CITATION=Ref.: 14 2; CITATION_NUMBERS=[14,2]; REFERENCE=Ref.: 14 2; DETAILS_JSON={"cas_number":"633-96-5","citation":"Ref.: 14 2","dose":"emopoiesis in the spleen) or other haematological parameters at 2.5 mg/kg/day.","duration":"Sub-chronic","effect":"emopoiesis in the spleen) or other haematological parameters at 2.5 mg/kg/day. In males treated with 10 mg/kg/day, increased organ/body weight ratio in the spleen was noted, which correlated to microscopic findings (extramedullary hemopoiesis in the spleen in all animals treated with 5-10 mg/kg/day. No test article related macroscopic findings were observed during necropsy. With regard to the results obtained this, especially to changes in haematological parameters of males, the No-Observable-Adverse-Effect-Level (NOAEL) of Acid Orange 7 [D&C Orange 4 (C.I. 15510)] was considered to be in the general range around 2.5 mg/kg body weight/day. This dose led to borderline effects on met-hemoglobin and reticulocytes counts without concurrent effects on the spleen. The NOAEL for females could be set to 2.5 mg/kg/body weight/ day. Ref.: 14 2.3.8. Sub-chronic dermal toxicity 3 animals each group (rabbits) were used for this assay. The test material (FDA certified material) was applied to the depilated skin of rabbits. Daily application","endpoint":"repeated dose toxicity","ingredient":"codes","loael_value":"","noael_unit":"mg/kg","noael_value":"2.5","page":8,"route":"dermal","species":"rabbit","study_id":"out259_en_noael_001"} |
| UnifiedCodex:SCCNFP:beta.noael_studies | repeated dose toxicity | 2.5 | mg/kg | rabbit | dermal | Sub-chronic | repeated dose toxicity | SOURCE_SUBDIR=out259_en; REPORT_TITLE=OPINION OF THE SCIENTIFIC COMMITTEE ON COSMETIC PRODUCTS AND NON-FOOD PRODUCTS INTENDED FOR CONSUMERS CONCERNING ACID ORANGE 7 COLIPA n° C15; OPINION_NUMBER=SCCNFP/0785/04; COMMITTEE=SCCNFP; REPORT_DATE=adopted by the SCCNFP on 23 April 2004; VALUE_TEXT=2.5; DOSE=een in all animals treated with 5-10 mg/kg/day.; EFFECT=een in all animals treated with 5-10 mg/kg/day. No test article related macroscopic findings were observed during necropsy. With regard to the results obtained this, especially to changes in haematological parameters of males, the No-Observable-Adverse-Effect-Level (NOAEL) of Acid Orange 7 [D&C Orange 4 (C.I. 15510)] was considered to be in the general range around 2.5 mg/kg body weight/day. This dose led to borderline effects on met-hemoglobin and reticulocytes counts without concurrent effects on the spleen. The NOAEL for females could be set to 2.5 mg/kg/body weight/ day. Ref.: 14 2.3.8. Sub-chronic dermal toxicity 3 animals each group (rabbits) were used for this assay. The test material (FDA certified material) was applied to the depilated skin of rabbits. Daily applications were made to intact and abraded skin for 21 days and to intact skin for 90 days. The colour was applied at two concentrations 0.1 and 1.0 %, dissolved in water as well as USP White Ointment. Control groups were treated with respective media. Results; CITATION=Ref.: 14 2; CITATION_NUMBERS=[14,2]; REFERENCE=Ref.: 14 2; DETAILS_JSON={"cas_number":"633-96-5","citation":"Ref.: 14 2","dose":"een in all animals treated with 5-10 mg/kg/day.","duration":"Sub-chronic","effect":"een in all animals treated with 5-10 mg/kg/day. No test article related macroscopic findings were observed during necropsy. With regard to the results obtained this, especially to changes in haematological parameters of males, the No-Observable-Adverse-Effect-Level (NOAEL) of Acid Orange 7 [D&C Orange 4 (C.I. 15510)] was considered to be in the general range around 2.5 mg/kg body weight/day. This dose led to borderline effects on met-hemoglobin and reticulocytes counts without concurrent effects on the spleen. The NOAEL for females could be set to 2.5 mg/kg/body weight/ day. Ref.: 14 2.3.8. Sub-chronic dermal toxicity 3 animals each group (rabbits) were used for this assay. The test material (FDA certified material) was applied to the depilated skin of rabbits. Daily applications were made to intact and abraded skin for 21 days and to intact skin for 90 days. The colour was applied at two concentrations 0.1 and 1.0 %, dissolved in water as well as USP White Ointment. Control groups were treated with respective media. Results","endpoint":"repeated dose toxicity","ingredient":"codes","loael_value":"","noael_unit":"mg/kg","noael_value":"2.5","page":8,"route":"dermal","species":"rabbit","study_id":"out259_en_noael_002"} |
UnifiedCodex:SCCS_SHADOW:beta.noael_studies 14 endpoints
| Source | Endpoint Type | Value | Unit | Species | Route | Duration | Study Type | Reference |
|---|---|---|---|---|---|---|---|---|
| UnifiedCodex:SCCS_SHADOW:beta.noael_studies | - | 2.5 | mg/kg bw/day | - | - | - | - | SOURCE_SUBDIR=sccs_o_057; REPORT_TITLE=OPINION ON Acid Orange 7 COLIPA n° C15; OPINION_NUMBER=SCCS/1382/10; COMMITTEE=Scientific Committee on Consumer Safety (SCCS); REPORT_DATE=adopted on 23 April 2004; VALUE_TEXT=2.5; DOSE=hological (extramedullary hemopoiesis in the spleen) or other haematological parameters at 2.5 mg/kg bw/day.; EFFECT=hological (extramedullary hemopoiesis in the spleen) or other haematological parameters at 2.5 mg/kg bw/day. In males treated with 10 mg/kg bw/day, increased organ/body weight ratio in the spleen was noted, which correlated to microscopic findings (extramedullary hemopoiesis in the spleen in all animals treated with 5-10 mg/kg bw/day. No test article related macroscopic findings were observed during necropsy. With regard to the results obtained this, especially to changes in haematological parameters of males, the No Observed Adverse Effect Level (NOAEL) of Acid Orange 7 was considered to be in the general range around 2.5 mg/kg bw/day. This dose led to borderline effects on met-hemoglobin and reticulocytes counts without concurrent effects on the spleen. The NOAEL for females was set to 2.5 mg/kg bw/ day by the study authors. Ref.: 14 Comment It should be noted that at this dose, some slight early haematological effects (increased met-haemoglobin levels in males and increased reticulocytes count) are already observed. Even if there are in the upper limit; CITATION=Ref.: 14 Comment It should be noted that at this dose, some slight early haematological effects (increased met-haemoglobin levels in males and increased reticulocytes count) are already; CITATION_NUMBERS=[14]; REFERENCE=Ref.: 14 Comment It should be noted that at this dose, some slight early haematological effects (increased met-haemoglobin levels in males and increased reticulocytes count) are already; DETAILS_JSON={"cas_number":"633-96-5","citation":"Ref.: 14 Comment It should be noted that at this dose, some slight early haematological effects (increased met-haemoglobin levels in males and increased reticulocytes count) are already","dose":"hological (extramedullary hemopoiesis in the spleen) or other haematological parameters at 2.5 mg/kg bw/day.","duration":"","effect":"hological (extramedullary hemopoiesis in the spleen) or other haematological parameters at 2.5 mg/kg bw/day. In males treated with 10 mg/kg bw/day, increased organ/body weight ratio in the spleen was noted, which correlated to microscopic findings (extramedullary hemopoiesis in the spleen in all animals treated with 5-10 mg/kg bw/day. No test article related macroscopic findings were observed during necropsy. With regard to the results obtained this, especially to changes in haematological parameters of males, the No Observed Adverse Effect Level (NOAEL) of Acid Orange 7 was considered to be in the general range around 2.5 mg/kg bw/day. This dose led to borderline effects on met-hemoglobin and reticulocytes counts without concurrent effects on the spleen. The NOAEL for females was set to 2.5 mg/kg bw/ day by the study authors. Ref.: 14 Comment It should be noted that at this dose, some slight early haematological effects (increased met-haemoglobin levels in males and increased reticulocytes count) are already observed. Even if there are in the upper limit","endpoint":"","ingredient":"was submitted in September 2003 by COLIPA 1.","loael_value":"","noael_unit":"mg/kg bw/day","noael_value":"2.5","page":18,"route":"","species":"","study_id":"sccs_o_057_noael_001"} |
| UnifiedCodex:SCCS_SHADOW:beta.noael_studies | - | 2.5 | mg/kg bw/day | - | - | - | - | SOURCE_SUBDIR=sccs_o_057; REPORT_TITLE=OPINION ON Acid Orange 7 COLIPA n° C15; OPINION_NUMBER=SCCS/1382/10; COMMITTEE=Scientific Committee on Consumer Safety (SCCS); REPORT_DATE=adopted on 23 April 2004; VALUE_TEXT=2.5; DOSE=sis in the spleen) or other haematological parameters at 2.5 mg/kg bw/day.; EFFECT=sis in the spleen) or other haematological parameters at 2.5 mg/kg bw/day. In males treated with 10 mg/kg bw/day, increased organ/body weight ratio in the spleen was noted, which correlated to microscopic findings (extramedullary hemopoiesis in the spleen in all animals treated with 5-10 mg/kg bw/day. No test article related macroscopic findings were observed during necropsy. With regard to the results obtained this, especially to changes in haematological parameters of males, the No Observed Adverse Effect Level (NOAEL) of Acid Orange 7 was considered to be in the general range around 2.5 mg/kg bw/day. This dose led to borderline effects on met-hemoglobin and reticulocytes counts without concurrent effects on the spleen. The NOAEL for females was set to 2.5 mg/kg bw/ day by the study authors. Ref.: 14 Comment It should be noted that at this dose, some slight early haematological effects (increased met-haemoglobin levels in males and increased reticulocytes count) are already observed. Even if there are in the upper limits of th; CITATION=Ref.: 14 Comment It should be noted that at this dose, some slight early haematological effects (increased met-haemoglobin levels in males and increased reticulocytes count) are already; CITATION_NUMBERS=[14]; REFERENCE=Ref.: 14 Comment It should be noted that at this dose, some slight early haematological effects (increased met-haemoglobin levels in males and increased reticulocytes count) are already; DETAILS_JSON={"cas_number":"633-96-5","citation":"Ref.: 14 Comment It should be noted that at this dose, some slight early haematological effects (increased met-haemoglobin levels in males and increased reticulocytes count) are already","dose":"sis in the spleen) or other haematological parameters at 2.5 mg/kg bw/day.","duration":"","effect":"sis in the spleen) or other haematological parameters at 2.5 mg/kg bw/day. In males treated with 10 mg/kg bw/day, increased organ/body weight ratio in the spleen was noted, which correlated to microscopic findings (extramedullary hemopoiesis in the spleen in all animals treated with 5-10 mg/kg bw/day. No test article related macroscopic findings were observed during necropsy. With regard to the results obtained this, especially to changes in haematological parameters of males, the No Observed Adverse Effect Level (NOAEL) of Acid Orange 7 was considered to be in the general range around 2.5 mg/kg bw/day. This dose led to borderline effects on met-hemoglobin and reticulocytes counts without concurrent effects on the spleen. The NOAEL for females was set to 2.5 mg/kg bw/ day by the study authors. Ref.: 14 Comment It should be noted that at this dose, some slight early haematological effects (increased met-haemoglobin levels in males and increased reticulocytes count) are already observed. Even if there are in the upper limits of th","endpoint":"","ingredient":"was submitted in September 2003 by COLIPA 1.","loael_value":"","noael_unit":"mg/kg bw/day","noael_value":"2.5","page":18,"route":"","species":"","study_id":"sccs_o_057_noael_002"} |
| UnifiedCodex:SCCS_SHADOW:beta.noael_studies | - | 2.5 | mg/kg bw/ day | rabbit | dermal | - | - | SOURCE_SUBDIR=sccs_o_057; REPORT_TITLE=OPINION ON Acid Orange 7 COLIPA n° C15; OPINION_NUMBER=SCCS/1382/10; COMMITTEE=Scientific Committee on Consumer Safety (SCCS); REPORT_DATE=adopted on 23 April 2004; VALUE_TEXT=2.5; DOSE=xtramedullary hemopoiesis in the spleen in all animals treated with 5-10 mg/kg bw/day.; EFFECT=xtramedullary hemopoiesis in the spleen in all animals treated with 5-10 mg/kg bw/day. No test article related macroscopic findings were observed during necropsy. With regard to the results obtained this, especially to changes in haematological parameters of males, the No Observed Adverse Effect Level (NOAEL) of Acid Orange 7 was considered to be in the general range around 2.5 mg/kg bw/day. This dose led to borderline effects on met-hemoglobin and reticulocytes counts without concurrent effects on the spleen. The NOAEL for females was set to 2.5 mg/kg bw/ day by the study authors. Ref.: 14 Comment It should be noted that at this dose, some slight early haematological effects (increased met-haemoglobin levels in males and increased reticulocytes count) are already observed. Even if there are in the upper limits of the historical control values, this finding could be test article related. Therefore, the dose of 2.5 mg/kg bw /day is considered as the LOAEL. 90–day dermal toxicity 3 animals each group (rabbits) were used for thi; CITATION=Ref.: 14 Comment It should be noted that at this dose, some slight early haematological effects (increased met-haemoglobin levels in males and increased reticulocytes count) are already; CITATION_NUMBERS=[14]; REFERENCE=Ref.: 14 Comment It should be noted that at this dose, some slight early haematological effects (increased met-haemoglobin levels in males and increased reticulocytes count) are already; DETAILS_JSON={"cas_number":"633-96-5","citation":"Ref.: 14 Comment It should be noted that at this dose, some slight early haematological effects (increased met-haemoglobin levels in males and increased reticulocytes count) are already","dose":"xtramedullary hemopoiesis in the spleen in all animals treated with 5-10 mg/kg bw/day.","duration":"","effect":"xtramedullary hemopoiesis in the spleen in all animals treated with 5-10 mg/kg bw/day. No test article related macroscopic findings were observed during necropsy. With regard to the results obtained this, especially to changes in haematological parameters of males, the No Observed Adverse Effect Level (NOAEL) of Acid Orange 7 was considered to be in the general range around 2.5 mg/kg bw/day. This dose led to borderline effects on met-hemoglobin and reticulocytes counts without concurrent effects on the spleen. The NOAEL for females was set to 2.5 mg/kg bw/ day by the study authors. Ref.: 14 Comment It should be noted that at this dose, some slight early haematological effects (increased met-haemoglobin levels in males and increased reticulocytes count) are already observed. Even if there are in the upper limits of the historical control values, this finding could be test article related. Therefore, the dose of 2.5 mg/kg bw /day is considered as the LOAEL. 90–day dermal toxicity 3 animals each group (rabbits) were used for thi","endpoint":"","ingredient":"was submitted in September 2003 by COLIPA 1.","loael_value":"","noael_unit":"mg/kg bw/ day","noael_value":"2.5","page":18,"route":"dermal","species":"rabbit","study_id":"sccs_o_057_noael_003"} |
| UnifiedCodex:SCCS_SHADOW:beta.noael_studies | - | 5 | mg/kg bw/day | human | - | - | - | SOURCE_SUBDIR=sccs_o_057; REPORT_TITLE=OPINION ON Acid Orange 7 COLIPA n° C15; OPINION_NUMBER=SCCS/1382/10; COMMITTEE=Scientific Committee on Consumer Safety (SCCS); REPORT_DATE=adopted on 23 April 2004; VALUE_TEXT=5; DOSE=Total resorptions were observed in 2 females in the high dose group.; EFFECT=consumption was also observed. Total resorptions were observed in 2 females in the high dose group. In the females treated at the dose of 40 and 320 mg/kg bw/day, a significant dose-related increased spleen weights was observed. Foetal toxicity: No abnormalities related to the treatment were observed in any foetuses. In the foetuses of group treated at 1000 mg/kg bw/day (dose not used), a slight decrease in the mean body weight was observed. Conclusion Based on the result, the No-Observable-Adverse-Effect-Level (NOAEL) of Acid Orange 7 was considered to be 5 mg/kg bw/day for the maternal organism and 320 mg/kg bw/day for the foetal organism. Ref.: 19 3.3.9. Toxicokinetics No data submitted 3.3.10. Photo-induced toxicity 3.3.10.1. Phototoxicity / photoirritation and photosensitisation No data submitted 3.3.10.2. Phototoxicity / photomutagenicity / photoclastogenicity No data submitted 3.3.11. Human data No data submitted 3.3.12. Special investigations No data submitted; CITATION=Ref.: 19 3; CITATION_NUMBERS=[19,3]; REFERENCE=Ref.: 19 3; DETAILS_JSON={"cas_number":"633-96-5","citation":"Ref.: 19 3","dose":"Total resorptions were observed in 2 females in the high dose group.","duration":"","effect":"consumption was also observed. Total resorptions were observed in 2 females in the high dose group. In the females treated at the dose of 40 and 320 mg/kg bw/day, a significant dose-related increased spleen weights was observed. Foetal toxicity: No abnormalities related to the treatment were observed in any foetuses. In the foetuses of group treated at 1000 mg/kg bw/day (dose not used), a slight decrease in the mean body weight was observed. Conclusion Based on the result, the No-Observable-Adverse-Effect-Level (NOAEL) of Acid Orange 7 was considered to be 5 mg/kg bw/day for the maternal organism and 320 mg/kg bw/day for the foetal organism. Ref.: 19 3.3.9. Toxicokinetics No data submitted 3.3.10. Photo-induced toxicity 3.3.10.1. Phototoxicity / photoirritation and photosensitisation No data submitted 3.3.10.2. Phototoxicity / photomutagenicity / photoclastogenicity No data submitted 3.3.11. Human data No data submitted 3.3.12. Special investigations No data submitted","endpoint":"","ingredient":"was submitted in September 2003 by COLIPA 1.","loael_value":"","noael_unit":"mg/kg bw/day","noael_value":"5","page":24,"route":"","species":"human","study_id":"sccs_o_057_noael_004"} |
| UnifiedCodex:SCCS_SHADOW:beta.noael_studies | - | 2.5 | mg/kg bw/d | rat | oral | 13-weeks | - | SOURCE_SUBDIR=sccs_o_057; REPORT_TITLE=OPINION ON Acid Orange 7 COLIPA n° C15; OPINION_NUMBER=SCCS/1382/10; COMMITTEE=Scientific Committee on Consumer Safety (SCCS); REPORT_DATE=adopted on 23 April 2004; VALUE_TEXT=2.5; DOSE=The NOAEL of a 13-weeks oral toxicity study in rats, was set to 2.5 mg/kg bw/d by the study authors.; EFFECT=reference material. The colour content (measured as HPLC peak area?) of various batches, reported in the table above, may not represent Acid Orange 7 content. Purity and impurities of all batches is not documented. Colour content in one of the batches is only 91%, but impurities in this batch are not reported. The stability in of Acid Orange 7 in typical hair dye formulations is not reported. The stability in an oxidative environment has not been demonstrated. Toxicity Acid Orange 7 is of low acute toxicity. The NOAEL of a 13-weeks oral toxicity study in rats, was set to 2.5 mg/kg bw/d by the study authors. It should be noted that at this dose, some slight early haematological effects (increased met-haemoglobin levels in males and increased reticulocytes count) are already observed. Even if they are in the upper limits of the historical control values, this finding could be test article related. Therefore the dose of 2.5 mg/kg bw/d should be considered as a LOAEL. Studies of effects on embryo-foetal development lead to a NOAEL; CITATION_NUMBERS=[]; DETAILS_JSON={"cas_number":"633-96-5","citation":"","dose":"The NOAEL of a 13-weeks oral toxicity study in rats, was set to 2.5 mg/kg bw/d by the study authors.","duration":"13-weeks","effect":"reference material. The colour content (measured as HPLC peak area?) of various batches, reported in the table above, may not represent Acid Orange 7 content. Purity and impurities of all batches is not documented. Colour content in one of the batches is only 91%, but impurities in this batch are not reported. The stability in of Acid Orange 7 in typical hair dye formulations is not reported. The stability in an oxidative environment has not been demonstrated. Toxicity Acid Orange 7 is of low acute toxicity. The NOAEL of a 13-weeks oral toxicity study in rats, was set to 2.5 mg/kg bw/d by the study authors. It should be noted that at this dose, some slight early haematological effects (increased met-haemoglobin levels in males and increased reticulocytes count) are already observed. Even if they are in the upper limits of the historical control values, this finding could be test article related. Therefore the dose of 2.5 mg/kg bw/d should be considered as a LOAEL. Studies of effects on embryo-foetal development lead to a NOAEL","endpoint":"","ingredient":"was submitted in September 2003 by COLIPA 1.","loael_value":"","noael_unit":"mg/kg bw/d","noael_value":"2.5","page":25,"route":"oral","species":"rat","study_id":"sccs_o_057_noael_006"} |
| UnifiedCodex:SCCS_SHADOW:beta.noael_studies | - | 2.5 | mg/kg bw/day | - | - | - | - | SOURCE_SUBDIR=sccs_o_158; REPORT_TITLE=OPINION ON Acid Orange 7 COLIPA n° C15; OPINION_NUMBER=SCCS/1536/14; COMMITTEE=Scientific Committee on Consumer Safety (SCCS); REPORT_DATE=23 September 2014; VALUE_TEXT=2.5; DOSE=ramedullary hemopoiesis in the spleen) or other haematological parameters at 2.5 mg/kg bw/day.; EFFECT=ramedullary hemopoiesis in the spleen) or other haematological parameters at 2.5 mg/kg bw/day. In males treated with 10 mg/kg bw/day, increased organ/body weight ratio in the spleen was noted, which correlated to microscopic findings (extramedullary hemopoiesis) in the spleen in all animals treated with 5-10 mg/kg bw/day. No test article-related macroscopic findings were observed during necropsy. With regard to the results obtained in this study, especially to changes in the haematological parameters of males, the No Observed Adverse Effect Level (NOAEL) of Acid Orange 7 was considered to be in the general range of around 2.5 mg/kg bw/day. This dose led to borderline effects on met-hemoglobin and reticulocytes counts without concurrent effects on the spleen. Conclusion The NOAEL for females was set to 2.5 mg/kg bw/ day by the study authors. Ref.: 14 SCCS comment It should be noted that at this dose, some slight early haematological effects (increased met-haemoglobin levels in males and increased reticulocytes count) have been observed. Even if they are; CITATION=Ref.: 14 SCCS comment It should be noted that at this dose, some slight early haematological effects (increased met-haemoglobin levels in males and increased reticulocytes count) have be; CITATION_NUMBERS=[14]; REFERENCE=Ref.: 14 SCCS comment It should be noted that at this dose, some slight early haematological effects (increased met-haemoglobin levels in males and increased reticulocytes count) have be; DETAILS_JSON={"cas_number":"633-96-5","citation":"Ref.: 14 SCCS comment It should be noted that at this dose, some slight early haematological effects (increased met-haemoglobin levels in males and increased reticulocytes count) have be","dose":"ramedullary hemopoiesis in the spleen) or other haematological parameters at 2.5 mg/kg bw/day.","duration":"","effect":"ramedullary hemopoiesis in the spleen) or other haematological parameters at 2.5 mg/kg bw/day. In males treated with 10 mg/kg bw/day, increased organ/body weight ratio in the spleen was noted, which correlated to microscopic findings (extramedullary hemopoiesis) in the spleen in all animals treated with 5-10 mg/kg bw/day. No test article-related macroscopic findings were observed during necropsy. With regard to the results obtained in this study, especially to changes in the haematological parameters of males, the No Observed Adverse Effect Level (NOAEL) of Acid Orange 7 was considered to be in the general range of around 2.5 mg/kg bw/day. This dose led to borderline effects on met-hemoglobin and reticulocytes counts without concurrent effects on the spleen. Conclusion The NOAEL for females was set to 2.5 mg/kg bw/ day by the study authors. Ref.: 14 SCCS comment It should be noted that at this dose, some slight early haematological effects (increased met-haemoglobin levels in males and increased reticulocytes count) have been observed. Even if they are","endpoint":"","ingredient":"Sodium 4-[(2-hydroxy-1-naphthyl)azo]benzene sulfonate (CAS No 633-96-5","loael_value":"","noael_unit":"mg/kg bw/day","noael_value":"2.5","page":21,"route":"","species":"","study_id":"sccs_o_158_noael_001"} |
| UnifiedCodex:SCCS_SHADOW:beta.noael_studies | - | 2.5 | mg/kg bw/day | - | - | - | - | SOURCE_SUBDIR=sccs_o_158; REPORT_TITLE=OPINION ON Acid Orange 7 COLIPA n° C15; OPINION_NUMBER=SCCS/1536/14; COMMITTEE=Scientific Committee on Consumer Safety (SCCS); REPORT_DATE=23 September 2014; VALUE_TEXT=2.5; DOSE=een) or other haematological parameters at 2.5 mg/kg bw/day.; EFFECT=een) or other haematological parameters at 2.5 mg/kg bw/day. In males treated with 10 mg/kg bw/day, increased organ/body weight ratio in the spleen was noted, which correlated to microscopic findings (extramedullary hemopoiesis) in the spleen in all animals treated with 5-10 mg/kg bw/day. No test article-related macroscopic findings were observed during necropsy. With regard to the results obtained in this study, especially to changes in the haematological parameters of males, the No Observed Adverse Effect Level (NOAEL) of Acid Orange 7 was considered to be in the general range of around 2.5 mg/kg bw/day. This dose led to borderline effects on met-hemoglobin and reticulocytes counts without concurrent effects on the spleen. Conclusion The NOAEL for females was set to 2.5 mg/kg bw/ day by the study authors. Ref.: 14 SCCS comment It should be noted that at this dose, some slight early haematological effects (increased met-haemoglobin levels in males and increased reticulocytes count) have been observed. Even if they are in the; CITATION=Ref.: 14 SCCS comment It should be noted that at this dose, some slight early haematological effects (increased met-haemoglobin levels in males and increased reticulocytes count) have be; CITATION_NUMBERS=[14]; REFERENCE=Ref.: 14 SCCS comment It should be noted that at this dose, some slight early haematological effects (increased met-haemoglobin levels in males and increased reticulocytes count) have be; DETAILS_JSON={"cas_number":"633-96-5","citation":"Ref.: 14 SCCS comment It should be noted that at this dose, some slight early haematological effects (increased met-haemoglobin levels in males and increased reticulocytes count) have be","dose":"een) or other haematological parameters at 2.5 mg/kg bw/day.","duration":"","effect":"een) or other haematological parameters at 2.5 mg/kg bw/day. In males treated with 10 mg/kg bw/day, increased organ/body weight ratio in the spleen was noted, which correlated to microscopic findings (extramedullary hemopoiesis) in the spleen in all animals treated with 5-10 mg/kg bw/day. No test article-related macroscopic findings were observed during necropsy. With regard to the results obtained in this study, especially to changes in the haematological parameters of males, the No Observed Adverse Effect Level (NOAEL) of Acid Orange 7 was considered to be in the general range of around 2.5 mg/kg bw/day. This dose led to borderline effects on met-hemoglobin and reticulocytes counts without concurrent effects on the spleen. Conclusion The NOAEL for females was set to 2.5 mg/kg bw/ day by the study authors. Ref.: 14 SCCS comment It should be noted that at this dose, some slight early haematological effects (increased met-haemoglobin levels in males and increased reticulocytes count) have been observed. Even if they are in the","endpoint":"","ingredient":"Sodium 4-[(2-hydroxy-1-naphthyl)azo]benzene sulfonate (CAS No 633-96-5","loael_value":"","noael_unit":"mg/kg bw/day","noael_value":"2.5","page":21,"route":"","species":"","study_id":"sccs_o_158_noael_002"} |
| UnifiedCodex:SCCS_SHADOW:beta.noael_studies | - | 2.5 | mg/kg bw/ day | rabbit | dermal | - | - | SOURCE_SUBDIR=sccs_o_158; REPORT_TITLE=OPINION ON Acid Orange 7 COLIPA n° C15; OPINION_NUMBER=SCCS/1536/14; COMMITTEE=Scientific Committee on Consumer Safety (SCCS); REPORT_DATE=23 September 2014; VALUE_TEXT=2.5; DOSE=the spleen in all animals treated with 5-10 mg/kg bw/day.; EFFECT=the spleen in all animals treated with 5-10 mg/kg bw/day. No test article-related macroscopic findings were observed during necropsy. With regard to the results obtained in this study, especially to changes in the haematological parameters of males, the No Observed Adverse Effect Level (NOAEL) of Acid Orange 7 was considered to be in the general range of around 2.5 mg/kg bw/day. This dose led to borderline effects on met-hemoglobin and reticulocytes counts without concurrent effects on the spleen. Conclusion The NOAEL for females was set to 2.5 mg/kg bw/ day by the study authors. Ref.: 14 SCCS comment It should be noted that at this dose, some slight early haematological effects (increased met-haemoglobin levels in males and increased reticulocytes count) have been observed. Even if they are in the upper limits of the historical control values, this finding could be test article related. Therefore, the dose of 2.5 mg/kg bw /day is considered as the LOAEL. 90–day dermal toxicity 3 animals per group (rabbits) were used for t; CITATION=Ref.: 14 SCCS comment It should be noted that at this dose, some slight early haematological effects (increased met-haemoglobin levels in males and increased reticulocytes count) have be; CITATION_NUMBERS=[14]; REFERENCE=Ref.: 14 SCCS comment It should be noted that at this dose, some slight early haematological effects (increased met-haemoglobin levels in males and increased reticulocytes count) have be; DETAILS_JSON={"cas_number":"633-96-5","citation":"Ref.: 14 SCCS comment It should be noted that at this dose, some slight early haematological effects (increased met-haemoglobin levels in males and increased reticulocytes count) have be","dose":"the spleen in all animals treated with 5-10 mg/kg bw/day.","duration":"","effect":"the spleen in all animals treated with 5-10 mg/kg bw/day. No test article-related macroscopic findings were observed during necropsy. With regard to the results obtained in this study, especially to changes in the haematological parameters of males, the No Observed Adverse Effect Level (NOAEL) of Acid Orange 7 was considered to be in the general range of around 2.5 mg/kg bw/day. This dose led to borderline effects on met-hemoglobin and reticulocytes counts without concurrent effects on the spleen. Conclusion The NOAEL for females was set to 2.5 mg/kg bw/ day by the study authors. Ref.: 14 SCCS comment It should be noted that at this dose, some slight early haematological effects (increased met-haemoglobin levels in males and increased reticulocytes count) have been observed. Even if they are in the upper limits of the historical control values, this finding could be test article related. Therefore, the dose of 2.5 mg/kg bw /day is considered as the LOAEL. 90–day dermal toxicity 3 animals per group (rabbits) were used for t","endpoint":"","ingredient":"Sodium 4-[(2-hydroxy-1-naphthyl)azo]benzene sulfonate (CAS No 633-96-5","loael_value":"","noael_unit":"mg/kg bw/ day","noael_value":"2.5","page":21,"route":"dermal","species":"rabbit","study_id":"sccs_o_158_noael_003"} |
| UnifiedCodex:SCCS_SHADOW:beta.noael_studies | - | 5 | mg/kg bw/day | human | - | - | - | SOURCE_SUBDIR=sccs_o_158; REPORT_TITLE=OPINION ON Acid Orange 7 COLIPA n° C15; OPINION_NUMBER=SCCS/1536/14; COMMITTEE=Scientific Committee on Consumer Safety (SCCS); REPORT_DATE=23 September 2014; VALUE_TEXT=5; DOSE=Total resorptions were observed in 2 females in the high dose group.; EFFECT=umption was also observed. Total resorptions were observed in 2 females in the high dose group. In the females treated at the dose of 40 and 320 mg/kg bw/day, a significant dose-related increased spleen weights was observed. Foetal toxicity: No abnormalities related to the treatment were observed in any foetuses. In the foetuses of the group treated at 1000 mg/kg bw/day (dose not used), a slight decrease in the mean body weight was observed. Conclusion Based on the result, the No-Observable-Adverse-Effect-Level (NOAEL) of Acid Orange 7 was considered to be 5 mg/kg bw/day for the maternal organism and 320 mg/kg bw/day for the foetal organism. Ref.: 19 3.3.9. Toxicokinetics No data submitted 3.3.10. Photo-induced toxicity 3.3.10.1. Phototoxicity / photoirritation and photosensitisation No data submitted 3.3.10.2. Phototoxicity / photomutagenicity / photoclastogenicity No data submitted 3.3.11. Human data No data submitted 3.3.12. Special investigations No data submitted; CITATION=Ref.: 19 3; CITATION_NUMBERS=[19,3]; REFERENCE=Ref.: 19 3; DETAILS_JSON={"cas_number":"633-96-5","citation":"Ref.: 19 3","dose":"Total resorptions were observed in 2 females in the high dose group.","duration":"","effect":"umption was also observed. Total resorptions were observed in 2 females in the high dose group. In the females treated at the dose of 40 and 320 mg/kg bw/day, a significant dose-related increased spleen weights was observed. Foetal toxicity: No abnormalities related to the treatment were observed in any foetuses. In the foetuses of the group treated at 1000 mg/kg bw/day (dose not used), a slight decrease in the mean body weight was observed. Conclusion Based on the result, the No-Observable-Adverse-Effect-Level (NOAEL) of Acid Orange 7 was considered to be 5 mg/kg bw/day for the maternal organism and 320 mg/kg bw/day for the foetal organism. Ref.: 19 3.3.9. Toxicokinetics No data submitted 3.3.10. Photo-induced toxicity 3.3.10.1. Phototoxicity / photoirritation and photosensitisation No data submitted 3.3.10.2. Phototoxicity / photomutagenicity / photoclastogenicity No data submitted 3.3.11. Human data No data submitted 3.3.12. Special investigations No data submitted","endpoint":"","ingredient":"Sodium 4-[(2-hydroxy-1-naphthyl)azo]benzene sulfonate (CAS No 633-96-5","loael_value":"","noael_unit":"mg/kg bw/day","noael_value":"5","page":27,"route":"","species":"human","study_id":"sccs_o_158_noael_004"} |
| UnifiedCodex:SCCS_SHADOW:beta.noael_studies | - | 2.5 | mg/kg bw/d | rat | oral | 13-week | - | SOURCE_SUBDIR=sccs_o_158; REPORT_TITLE=OPINION ON Acid Orange 7 COLIPA n° C15; OPINION_NUMBER=SCCS/1536/14; COMMITTEE=Scientific Committee on Consumer Safety (SCCS); REPORT_DATE=23 September 2014; VALUE_TEXT=2.5; DOSE=The NOAEL of a 13-week oral toxicity study in rats was set to 2.5 mg/kg bw/d by the study authors.; EFFECT=ion, because the content is determined only in terms of colour content. Thus, impurities with the same colour (chromophore groups) will also be measured together with the active substance. Impurities in one of the batches of Acid Orange 7 (colour content 91%) were not reported. Stability of Acid Orange 7 under oxidative conditions of use has not been reported. In addition, the stability in of Acid Orange 7 in typical hair dye formulations is not reported. Toxicity Acid Orange 7 is of low acute oral toxicity. The NOAEL of a 13-week oral toxicity study in rats was set to 2.5 mg/kg bw/d by the study authors. It should be noted that at this dose, some slight early haematological effects (increased met-haemoglobin levels in males and increased reticulocytes count) have already been observed. Even if these are in the upper limits of the historical control values, this finding could be test article-related. Therefore the dose of 2.5 mg/kg bw/d should be considered as a LOAEL. Studies of effects on embryo-foetal development lead to a N; CITATION_NUMBERS=[]; DETAILS_JSON={"cas_number":"633-96-5","citation":"","dose":"The NOAEL of a 13-week oral toxicity study in rats was set to 2.5 mg/kg bw/d by the study authors.","duration":"13-week","effect":"ion, because the content is determined only in terms of colour content. Thus, impurities with the same colour (chromophore groups) will also be measured together with the active substance. Impurities in one of the batches of Acid Orange 7 (colour content 91%) were not reported. Stability of Acid Orange 7 under oxidative conditions of use has not been reported. In addition, the stability in of Acid Orange 7 in typical hair dye formulations is not reported. Toxicity Acid Orange 7 is of low acute oral toxicity. The NOAEL of a 13-week oral toxicity study in rats was set to 2.5 mg/kg bw/d by the study authors. It should be noted that at this dose, some slight early haematological effects (increased met-haemoglobin levels in males and increased reticulocytes count) have already been observed. Even if these are in the upper limits of the historical control values, this finding could be test article-related. Therefore the dose of 2.5 mg/kg bw/d should be considered as a LOAEL. Studies of effects on embryo-foetal development lead to a N","endpoint":"","ingredient":"Sodium 4-[(2-hydroxy-1-naphthyl)azo]benzene sulfonate (CAS No 633-96-5","loael_value":"","noael_unit":"mg/kg bw/d","noael_value":"2.5","page":28,"route":"oral","species":"rat","study_id":"sccs_o_158_noael_006"} |
| UnifiedCodex:SCCS_SHADOW:beta.noael_studies | dermal absorption | =0.83 | mg/kg bw/d | rat | oral | 13-week | dermal absorption | SOURCE_SUBDIR=sccs_o_057; REPORT_TITLE=OPINION ON Acid Orange 7 COLIPA n° C15; OPINION_NUMBER=SCCS/1382/10; COMMITTEE=Scientific Committee on Consumer Safety (SCCS); REPORT_DATE=adopted on 23 April 2004; VALUE_TEXT== 0.83; DOSE=Safety evaluation (including calculation of the MoS) CALCULATION OF THE MARGIN OF SAFETY Acid Orange 7 (non-oxidative conditions) Absorption through the skin A (mean + 2SD) = 3.43 µg/cm² Skin Area surface SAS = 580 cm2 Dermal absorption per treatment SAS x A x 0.001 = 1.99 mg Typical body weight of human = 60 kg Systemic exposure dose (SED) SAS...; LOAEL_VALUE=2.5 mg/kg bw/d; EFFECT=25 3.3.13. Safety evaluation (including calculation of the MoS) CALCULATION OF THE MARGIN OF SAFETY Acid Orange 7 (non-oxidative conditions) Absorption through the skin A (mean + 2SD) = 3.43 µg/cm² Skin Area surface SAS = 580 cm2 Dermal absorption per treatment SAS x A x 0.001 = 1.99 mg Typical body weight of human = 60 kg Systemic exposure dose (SED) SAS x A x 0.001/60 = 0.033 mg/kg bw Lowest Observed Adverse Effect Level LOAEL = 2.5 mg/kg bw/d (13-week, oral, rat) Adjusted by factor 3 = 0.83 mg/kg bw/d MOS NOAEL / SED = 25 3.3.14. Discussion Physico-chemical properties Acid Orange 7 is intended for use in oxidative and non-oxidative hair dye formulations as a direct dye at a maximum concentration of 0.5%. Acid Orange 7 is also permitted to be used as a cosmetic colorant, listed as CI 15510 in Annex IV of the EU Cosmetic Directive. The content of Acid Orange 7 in the test materials has not been measured using a standard reference material. The colour content (measured as HPLC peak area?) of various batches, reported in; CITATION_NUMBERS=[]; DETAILS_JSON={"cas_number":"633-96-5","citation":"","dose":"Safety evaluation (including calculation of the MoS) CALCULATION OF THE MARGIN OF SAFETY Acid Orange 7 (non-oxidative conditions) Absorption through the skin A (mean + 2SD) = 3.43 µg/cm² Skin Area surface SAS = 580 cm2 Dermal absorption per treatment SAS x A x 0.001 = 1.99 mg Typical body weight of human = 60 kg Systemic exposure dose (SED) SAS...","duration":"13-week","effect":"25 3.3.13. Safety evaluation (including calculation of the MoS) CALCULATION OF THE MARGIN OF SAFETY Acid Orange 7 (non-oxidative conditions) Absorption through the skin A (mean + 2SD) = 3.43 µg/cm² Skin Area surface SAS = 580 cm2 Dermal absorption per treatment SAS x A x 0.001 = 1.99 mg Typical body weight of human = 60 kg Systemic exposure dose (SED) SAS x A x 0.001/60 = 0.033 mg/kg bw Lowest Observed Adverse Effect Level LOAEL = 2.5 mg/kg bw/d (13-week, oral, rat) Adjusted by factor 3 = 0.83 mg/kg bw/d MOS NOAEL / SED = 25 3.3.14. Discussion Physico-chemical properties Acid Orange 7 is intended for use in oxidative and non-oxidative hair dye formulations as a direct dye at a maximum concentration of 0.5%. Acid Orange 7 is also permitted to be used as a cosmetic colorant, listed as CI 15510 in Annex IV of the EU Cosmetic Directive. The content of Acid Orange 7 in the test materials has not been measured using a standard reference material. The colour content (measured as HPLC peak area?) of various batches, reported in","endpoint":"dermal absorption","ingredient":"was submitted in September 2003 by COLIPA 1.","loael_value":"2.5 mg/kg bw/d","noael_unit":"mg/kg bw/d","noael_value":"= 0.83","page":25,"route":"oral","species":"rat","study_id":"sccs_o_057_noael_005"} |
| UnifiedCodex:SCCS_SHADOW:beta.noael_studies | dermal absorption | 5 | mg/kg bw/d | rat | oral | 13-weeks | dermal absorption | SOURCE_SUBDIR=sccs_o_057; REPORT_TITLE=OPINION ON Acid Orange 7 COLIPA n° C15; OPINION_NUMBER=SCCS/1382/10; COMMITTEE=Scientific Committee on Consumer Safety (SCCS); REPORT_DATE=adopted on 23 April 2004; VALUE_TEXT=5; DOSE=NOAEL of a 13-weeks oral toxicity study in rats, was set to 2.5 mg/kg bw/d by the study authors.; LOAEL_VALUE=5 mg/kg bw/d; EFFECT=NOAEL of a 13-weeks oral toxicity study in rats, was set to 2.5 mg/kg bw/d by the study authors. It should be noted that at this dose, some slight early haematological effects (increased met-haemoglobin levels in males and increased reticulocytes count) are already observed. Even if they are in the upper limits of the historical control values, this finding could be test article related. Therefore the dose of 2.5 mg/kg bw/d should be considered as a LOAEL. Studies of effects on embryo-foetal development lead to a NOAEL of 5 mg/kg bw/d for maternal toxicity and 320 mg/kg bw/d for foetal toxicity. Irritation and sensitization The assessment of skin and eye irritation does not complying with the current standards; nevertheless, there is no reason to ask for a repetition of these studies. According to the studies available, Acid Orange 7 is not irritating to rabbit skin and not a sensitiser. Percutaneous absorption Under the reported conditions, the dermal absorption of Acid Orange 7 is 1.13 ± 1.15 µg/cm² or 1.25 ± 1.20% (mean v; CITATION_NUMBERS=[]; DETAILS_JSON={"cas_number":"633-96-5","citation":"","dose":"NOAEL of a 13-weeks oral toxicity study in rats, was set to 2.5 mg/kg bw/d by the study authors.","duration":"13-weeks","effect":"NOAEL of a 13-weeks oral toxicity study in rats, was set to 2.5 mg/kg bw/d by the study authors. It should be noted that at this dose, some slight early haematological effects (increased met-haemoglobin levels in males and increased reticulocytes count) are already observed. Even if they are in the upper limits of the historical control values, this finding could be test article related. Therefore the dose of 2.5 mg/kg bw/d should be considered as a LOAEL. Studies of effects on embryo-foetal development lead to a NOAEL of 5 mg/kg bw/d for maternal toxicity and 320 mg/kg bw/d for foetal toxicity. Irritation and sensitization The assessment of skin and eye irritation does not complying with the current standards; nevertheless, there is no reason to ask for a repetition of these studies. According to the studies available, Acid Orange 7 is not irritating to rabbit skin and not a sensitiser. Percutaneous absorption Under the reported conditions, the dermal absorption of Acid Orange 7 is 1.13 ± 1.15 µg/cm² or 1.25 ± 1.20% (mean v","endpoint":"dermal absorption","ingredient":"was submitted in September 2003 by COLIPA 1.","loael_value":"5 mg/kg bw/d","noael_unit":"mg/kg bw/d","noael_value":"5","page":25,"route":"oral","species":"rat","study_id":"sccs_o_057_noael_007"} |
| UnifiedCodex:SCCS_SHADOW:beta.noael_studies | dermal absorption | 50 | % | rat | oral | 13-week | dermal absorption | SOURCE_SUBDIR=sccs_o_158; REPORT_TITLE=OPINION ON Acid Orange 7 COLIPA n° C15; OPINION_NUMBER=SCCS/1536/14; COMMITTEE=Scientific Committee on Consumer Safety (SCCS); REPORT_DATE=23 September 2014; VALUE_TEXT=50; DOSE=ncluding calculation of the MoS) CALCULATION OF THE MARGIN OF SAFETY Acid Orange 7 (non-oxidative conditions) Absorption through the skin A (mean + 1 SD) = 0.25 µg/cm² Skin Area surface SAS = 580 cm2 Dermal absorption per treatment SAS x A x 0.001 = 0.145 mg Typical body weight of human = 60 kg Systemic exposure dose (SED) SAS x A x 0.001/60 = 0...; LOAEL_VALUE=2.5 mg/kg bw/d; EFFECT=ncluding calculation of the MoS) CALCULATION OF THE MARGIN OF SAFETY Acid Orange 7 (non-oxidative conditions) Absorption through the skin A (mean + 1 SD) = 0.25 µg/cm² Skin Area surface SAS = 580 cm2 Dermal absorption per treatment SAS x A x 0.001 = 0.145 mg Typical body weight of human = 60 kg Systemic exposure dose (SED) SAS x A x 0.001/60 = 0.0024 mg/kg bw Lowest Observed Adverse Effect Level LOAEL = 2.5 mg/kg bw/d (13-week, oral, rat) Adjusted by factor 3 = 0.83 mg/kg bw/d Bioavailability 50% = 0.415 MoS NOAEL / SED = 172 3.3.14. Discussion Physico-chemical properties Acid Orange 7 is intended for use in oxidative and non-oxidative hair dye formulations as a direct dye at a maximum concentration of 0.5%. Acid Orange 7 is also permitted to be used as a cosmetic colorant, listed as CI 15510 in Annex IV of the EU Cosmetic Directive. The reported Acid Orange 7 content in various batches of test material should be considered semi-quantitative determination, because the content is determined only in terms of colour content; CITATION_NUMBERS=[]; DETAILS_JSON={"cas_number":"633-96-5","citation":"","dose":"ncluding calculation of the MoS) CALCULATION OF THE MARGIN OF SAFETY Acid Orange 7 (non-oxidative conditions) Absorption through the skin A (mean + 1 SD) = 0.25 µg/cm² Skin Area surface SAS = 580 cm2 Dermal absorption per treatment SAS x A x 0.001 = 0.145 mg Typical body weight of human = 60 kg Systemic exposure dose (SED) SAS x A x 0.001/60 = 0...","duration":"13-week","effect":"ncluding calculation of the MoS) CALCULATION OF THE MARGIN OF SAFETY Acid Orange 7 (non-oxidative conditions) Absorption through the skin A (mean + 1 SD) = 0.25 µg/cm² Skin Area surface SAS = 580 cm2 Dermal absorption per treatment SAS x A x 0.001 = 0.145 mg Typical body weight of human = 60 kg Systemic exposure dose (SED) SAS x A x 0.001/60 = 0.0024 mg/kg bw Lowest Observed Adverse Effect Level LOAEL = 2.5 mg/kg bw/d (13-week, oral, rat) Adjusted by factor 3 = 0.83 mg/kg bw/d Bioavailability 50% = 0.415 MoS NOAEL / SED = 172 3.3.14. Discussion Physico-chemical properties Acid Orange 7 is intended for use in oxidative and non-oxidative hair dye formulations as a direct dye at a maximum concentration of 0.5%. Acid Orange 7 is also permitted to be used as a cosmetic colorant, listed as CI 15510 in Annex IV of the EU Cosmetic Directive. The reported Acid Orange 7 content in various batches of test material should be considered semi-quantitative determination, because the content is determined only in terms of colour content","endpoint":"dermal absorption","ingredient":"Sodium 4-[(2-hydroxy-1-naphthyl)azo]benzene sulfonate (CAS No 633-96-5","loael_value":"2.5 mg/kg bw/d","noael_unit":"%","noael_value":"50","page":28,"route":"oral","species":"rat","study_id":"sccs_o_158_noael_005"} |
| UnifiedCodex:SCCS_SHADOW:beta.noael_studies | dermal absorption | 5 | mg/kg bw/d | rat | oral | 13-week | dermal absorption | SOURCE_SUBDIR=sccs_o_158; REPORT_TITLE=OPINION ON Acid Orange 7 COLIPA n° C15; OPINION_NUMBER=SCCS/1536/14; COMMITTEE=Scientific Committee on Consumer Safety (SCCS); REPORT_DATE=23 September 2014; VALUE_TEXT=5; DOSE=L of a 13-week oral toxicity study in rats was set to 2.5 mg/kg bw/d by the study authors.; LOAEL_VALUE=5 mg/kg bw/d; EFFECT=L of a 13-week oral toxicity study in rats was set to 2.5 mg/kg bw/d by the study authors. It should be noted that at this dose, some slight early haematological effects (increased met-haemoglobin levels in males and increased reticulocytes count) have already been observed. Even if these are in the upper limits of the historical control values, this finding could be test article-related. Therefore the dose of 2.5 mg/kg bw/d should be considered as a LOAEL. Studies of effects on embryo-foetal development lead to a NOAEL of 5 mg/kg bw/d for maternal toxicity and 320 mg/kg bw/d for foetal toxicity. Irritation and sensitisation The assessment of skin and eye irritation does not comply with the current standards. According to the studies available, Acid Orange 7 is considered a mild skin irritant. Based on the data submitted, eye irritation potential cannot be evaluated. Based on the result in the available studies, Acid Orange 7 is not a skin sensitiser. Percutaneous absorption For the calculation of MoS, the mean+ 1 SD dermal ab; CITATION_NUMBERS=[]; DETAILS_JSON={"cas_number":"633-96-5","citation":"","dose":"L of a 13-week oral toxicity study in rats was set to 2.5 mg/kg bw/d by the study authors.","duration":"13-week","effect":"L of a 13-week oral toxicity study in rats was set to 2.5 mg/kg bw/d by the study authors. It should be noted that at this dose, some slight early haematological effects (increased met-haemoglobin levels in males and increased reticulocytes count) have already been observed. Even if these are in the upper limits of the historical control values, this finding could be test article-related. Therefore the dose of 2.5 mg/kg bw/d should be considered as a LOAEL. Studies of effects on embryo-foetal development lead to a NOAEL of 5 mg/kg bw/d for maternal toxicity and 320 mg/kg bw/d for foetal toxicity. Irritation and sensitisation The assessment of skin and eye irritation does not comply with the current standards. According to the studies available, Acid Orange 7 is considered a mild skin irritant. Based on the data submitted, eye irritation potential cannot be evaluated. Based on the result in the available studies, Acid Orange 7 is not a skin sensitiser. Percutaneous absorption For the calculation of MoS, the mean+ 1 SD dermal ab","endpoint":"dermal absorption","ingredient":"Sodium 4-[(2-hydroxy-1-naphthyl)azo]benzene sulfonate (CAS No 633-96-5","loael_value":"5 mg/kg bw/d","noael_unit":"mg/kg bw/d","noael_value":"5","page":28,"route":"oral","species":"rat","study_id":"sccs_o_158_noael_007"} |
openFDA substances 4 endpoints
| Source | Endpoint Type | Value | Unit | Species | Route | Duration | Study Type | Reference |
|---|---|---|---|---|---|---|---|---|
| openFDA substances | FDA UNII substance identifier | Q1LIY3BO0U | UNII | - | - | - | chemical | {"approval_status":null,"molecular_formula":"C16H11N2O4S.Na","source_table":"substance_identifiers_fda","substance_class":"chemical","unii_code":"Q1LIY3BO0U"} |
| openFDA substances | FDA UNII substance identifier | Q1LIY3BO0U | UNII | - | - | - | chemical | {"approval_status":null,"molecular_formula":"C16H11N2O4S.Na","source_table":"substance_identifiers_fda","substance_class":"chemical","unii_code":"Q1LIY3BO0U"} |
| openFDA substances | FDA UNII substance identifier | Q1LIY3BO0U | UNII | - | - | - | chemical | {"approval_status":null,"molecular_formula":"C16H11N2O4S.Na","source_table":"substance_identifiers_fda","substance_class":"chemical","unii_code":"Q1LIY3BO0U"} |
| openFDA substances | FDA UNII substance identifier | Q1LIY3BO0U | UNII | - | - | - | chemical | {"approval_status":null,"molecular_formula":"C16H11N2O4S.Na","source_table":"substance_identifiers_fda","substance_class":"chemical","unii_code":"Q1LIY3BO0U"} |