NOAEL Studies
Colorant
D&C Red No. 6 NOAEL Studies
INCI: D&C RED NO. 6
CAS: 5858-81-1
Raw No Observed Adverse Effect Level endpoint records grouped by source. This page does not render calculated Margin of Safety values.
NTP_ICE_acute_oral 1 endpoint
| Source | Endpoint Type | Value | Unit | Species | Route | Duration | Study Type | Reference |
|---|---|---|---|---|---|---|---|---|
| NTP_ICE_acute_oral | LD50 | >10800 | mg/kg bw | Rat | oral | acute | Rat Acute Oral Toxicity | record_id=acute_oral_8024; row=11121; data_type=In Vivo; mixture=Chemical; chemical_name=FD&C Red No. 6; preferred_name=C.I. Pigment Red 57; dtxsid=DTXSID6064038; url_comptox=https://comptox.epa.gov/dashboard/chemical/details/DTXSID6064038; source_file=acute_oral.xlsx |
SCCNFP_vision_codex 8 endpoints
| Source | Endpoint Type | Value | Unit | Species | Route | Duration | Study Type | Reference |
|---|---|---|---|---|---|---|---|---|
| SCCNFP_vision_codex | NOAEL | =150 | mg/kg bw/day | rat | oral | chronic | NOAEL study | {"citation":"Ref.: 2 Chronic oral toxicity study in mice Groups of 60 males and 60 females that were exposed to concentrations of 0","dose":"hologists from the US Food and Drug Administration subsequently examined tissue sections from the kidneys of all treated rats, they concluded that Lithol Rubine B exacerbated a spontaneous kidney disease of aged rats (chronic progressive nephrosis) in the mid- and high-dose males and in the high-dose females.","effect":"hologists from the US Food and Drug Administration subsequently examined tissue sections from the kidneys of all treated rats, they concluded that Lithol Rubine B exacerbated a spontaneous kidney disease of aged rats (chronic progressive nephrosis) in the mid- and high-dose males and in the high-dose females. An acceleration of testicular changes (degeneration of the testicular tubules), common in ageing rats, was also reported in high-dose males, but the increased incidence was of no statistical significance. The NOAEL was 150 mg/kg bw/day. Ref.: 2 Chronic oral toxicity study in mice Groups of 60 males and 60 females that were exposed to concentrations of 0.05, 1 or 5 % Pigment Red 57 in their diet (approximately 75, 1500 or 7500 mg/kg bw/day, respectively) for 2 years, showed no changes in food consumption, body weight gain, or blood composition. At the end of the study, the weights of the brain, kidneys, liver and spleen were unaffected and there were no abnormalities evident on gross examination. The treated males showed inc","page":8,"pdf":"out281_en.pdf","row_type":"noael_study","study_id":"out281_en_noael_001"} |
| SCCNFP_vision_codex | NOAEL | =150 | mg/kg | rat | oral | 18 months | reproductive toxicity | {"citation":"Ref.: 3 2","dose":"ed 57 (calcium salt) (about 50 mg/kg bw/application) for 18 months.","effect":"ed 57 (calcium salt) (about 50 mg/kg bw/application) for 18 months. Tissues from the skin were microscopically examined, as were other tissues that appeared abnormal on gross examination. Ref.: 3 2.10. Special investigations No data 2.11. Safety evaluation Not applicable 2.12. Conclusions Pigment Red 57 (Lithol Rubine B and BK) is of low acute toxicity in rats and dogs. Repeated and chronic oral administration to rodents up to 2 years, showed the kidney as a primary target organ in the high doses. The lowest NOAEL (150 mg/kg/bw/day) was obtained in the 2 years toxicity study in rats performed with the F1-generation of parent-animals pretreated at the same dose levels. The SCF also used this study to derive an ADI for this compound. There is no indication for corrosivity or comedogenic effects on the skin. Also no irritation on mucous membranes was noted. From the results of the local lymph node assay it is concluded that Pigment Red 57 is not a skin-sensitiser. There was no convincing evidence of reproductive effects in r","page":16,"pdf":"out281_en.pdf","row_type":"noael_study","study_id":"out281_en_noael_002"} |
| SCCNFP_vision_codex | NOAEL | =150 | mg/kg bw/day | rat | oral | chronic | NOAEL study | {"citation":"Ref.: 2 Chronic oral toxicity study in mice Groups of 60 males and 60 females that were exposed to concentrations of 0","dose":"hologists from the US Food and Drug Administration subsequently examined tissue sections from the kidneys of all treated rats, they concluded that Lithol Rubine B exacerbated a spontaneous kidney disease of aged rats (chronic progressive nephrosis) in the mid- and high-dose males and in the high-dose females.","effect":"hologists from the US Food and Drug Administration subsequently examined tissue sections from the kidneys of all treated rats, they concluded that Lithol Rubine B exacerbated a spontaneous kidney disease of aged rats (chronic progressive nephrosis) in the mid- and high-dose males and in the high-dose females. An acceleration of testicular changes (degeneration of the testicular tubules), common in ageing rats, was also reported in high-dose males, but the increased incidence was of no statistical significance. The NOAEL was 150 mg/kg bw/day. Ref.: 2 Chronic oral toxicity study in mice Groups of 60 males and 60 females that were exposed to concentrations of 0.05, 1 or 5 % Pigment Red 57 in their diet (approximately 75, 1500 or 7500 mg/kg bw/day, respectively) for 2 years, showed no changes in food consumption, body weight gain, or blood composition. At the end of the study, the weights of the brain, kidneys, liver and spleen were unaffected and there were no abnormalities evident on gross examination. The treated males showed inc","page":8,"pdf":"out281_en.pdf","row_type":"noael_study","study_id":"out281_en_noael_001"} |
| SCCNFP_vision_codex | NOAEL | =150 | mg/kg | rat | oral | 18 months | reproductive toxicity | {"citation":"Ref.: 3 2","dose":"ed 57 (calcium salt) (about 50 mg/kg bw/application) for 18 months.","effect":"ed 57 (calcium salt) (about 50 mg/kg bw/application) for 18 months. Tissues from the skin were microscopically examined, as were other tissues that appeared abnormal on gross examination. Ref.: 3 2.10. Special investigations No data 2.11. Safety evaluation Not applicable 2.12. Conclusions Pigment Red 57 (Lithol Rubine B and BK) is of low acute toxicity in rats and dogs. Repeated and chronic oral administration to rodents up to 2 years, showed the kidney as a primary target organ in the high doses. The lowest NOAEL (150 mg/kg/bw/day) was obtained in the 2 years toxicity study in rats performed with the F1-generation of parent-animals pretreated at the same dose levels. The SCF also used this study to derive an ADI for this compound. There is no indication for corrosivity or comedogenic effects on the skin. Also no irritation on mucous membranes was noted. From the results of the local lymph node assay it is concluded that Pigment Red 57 is not a skin-sensitiser. There was no convincing evidence of reproductive effects in r","page":16,"pdf":"out281_en.pdf","row_type":"noael_study","study_id":"out281_en_noael_002"} |
| SCCNFP_vision_codex | NOAEL | =150 | mg/kg bw/day | rat | oral | chronic | NOAEL study | {"citation":"Ref.: 2 Chronic oral toxicity study in mice Groups of 60 males and 60 females that were exposed to concentrations of 0","dose":"hologists from the US Food and Drug Administration subsequently examined tissue sections from the kidneys of all treated rats, they concluded that Lithol Rubine B exacerbated a spontaneous kidney disease of aged rats (chronic progressive nephrosis) in the mid- and high-dose males and in the high-dose females.","effect":"hologists from the US Food and Drug Administration subsequently examined tissue sections from the kidneys of all treated rats, they concluded that Lithol Rubine B exacerbated a spontaneous kidney disease of aged rats (chronic progressive nephrosis) in the mid- and high-dose males and in the high-dose females. An acceleration of testicular changes (degeneration of the testicular tubules), common in ageing rats, was also reported in high-dose males, but the increased incidence was of no statistical significance. The NOAEL was 150 mg/kg bw/day. Ref.: 2 Chronic oral toxicity study in mice Groups of 60 males and 60 females that were exposed to concentrations of 0.05, 1 or 5 % Pigment Red 57 in their diet (approximately 75, 1500 or 7500 mg/kg bw/day, respectively) for 2 years, showed no changes in food consumption, body weight gain, or blood composition. At the end of the study, the weights of the brain, kidneys, liver and spleen were unaffected and there were no abnormalities evident on gross examination. The treated males showed inc","page":8,"pdf":"out281_en.pdf","row_type":"noael_study","study_id":"out281_en_noael_001"} |
| SCCNFP_vision_codex | NOAEL | =150 | mg/kg | rat | oral | 18 months | reproductive toxicity | {"citation":"Ref.: 3 2","dose":"ed 57 (calcium salt) (about 50 mg/kg bw/application) for 18 months.","effect":"ed 57 (calcium salt) (about 50 mg/kg bw/application) for 18 months. Tissues from the skin were microscopically examined, as were other tissues that appeared abnormal on gross examination. Ref.: 3 2.10. Special investigations No data 2.11. Safety evaluation Not applicable 2.12. Conclusions Pigment Red 57 (Lithol Rubine B and BK) is of low acute toxicity in rats and dogs. Repeated and chronic oral administration to rodents up to 2 years, showed the kidney as a primary target organ in the high doses. The lowest NOAEL (150 mg/kg/bw/day) was obtained in the 2 years toxicity study in rats performed with the F1-generation of parent-animals pretreated at the same dose levels. The SCF also used this study to derive an ADI for this compound. There is no indication for corrosivity or comedogenic effects on the skin. Also no irritation on mucous membranes was noted. From the results of the local lymph node assay it is concluded that Pigment Red 57 is not a skin-sensitiser. There was no convincing evidence of reproductive effects in r","page":16,"pdf":"out281_en.pdf","row_type":"noael_study","study_id":"out281_en_noael_002"} |
| SCCNFP_vision_codex | NOAEL | =150 | mg/kg bw/day | rat | oral | chronic | NOAEL study | {"citation":"Ref.: 2 Chronic oral toxicity study in mice Groups of 60 males and 60 females that were exposed to concentrations of 0","dose":"hologists from the US Food and Drug Administration subsequently examined tissue sections from the kidneys of all treated rats, they concluded that Lithol Rubine B exacerbated a spontaneous kidney disease of aged rats (chronic progressive nephrosis) in the mid- and high-dose males and in the high-dose females.","effect":"hologists from the US Food and Drug Administration subsequently examined tissue sections from the kidneys of all treated rats, they concluded that Lithol Rubine B exacerbated a spontaneous kidney disease of aged rats (chronic progressive nephrosis) in the mid- and high-dose males and in the high-dose females. An acceleration of testicular changes (degeneration of the testicular tubules), common in ageing rats, was also reported in high-dose males, but the increased incidence was of no statistical significance. The NOAEL was 150 mg/kg bw/day. Ref.: 2 Chronic oral toxicity study in mice Groups of 60 males and 60 females that were exposed to concentrations of 0.05, 1 or 5 % Pigment Red 57 in their diet (approximately 75, 1500 or 7500 mg/kg bw/day, respectively) for 2 years, showed no changes in food consumption, body weight gain, or blood composition. At the end of the study, the weights of the brain, kidneys, liver and spleen were unaffected and there were no abnormalities evident on gross examination. The treated males showed inc","page":8,"pdf":"out281_en.pdf","row_type":"noael_study","study_id":"out281_en_noael_001"} |
| SCCNFP_vision_codex | NOAEL | =150 | mg/kg | rat | oral | 18 months | reproductive toxicity | {"citation":"Ref.: 3 2","dose":"ed 57 (calcium salt) (about 50 mg/kg bw/application) for 18 months.","effect":"ed 57 (calcium salt) (about 50 mg/kg bw/application) for 18 months. Tissues from the skin were microscopically examined, as were other tissues that appeared abnormal on gross examination. Ref.: 3 2.10. Special investigations No data 2.11. Safety evaluation Not applicable 2.12. Conclusions Pigment Red 57 (Lithol Rubine B and BK) is of low acute toxicity in rats and dogs. Repeated and chronic oral administration to rodents up to 2 years, showed the kidney as a primary target organ in the high doses. The lowest NOAEL (150 mg/kg/bw/day) was obtained in the 2 years toxicity study in rats performed with the F1-generation of parent-animals pretreated at the same dose levels. The SCF also used this study to derive an ADI for this compound. There is no indication for corrosivity or comedogenic effects on the skin. Also no irritation on mucous membranes was noted. From the results of the local lymph node assay it is concluded that Pigment Red 57 is not a skin-sensitiser. There was no convincing evidence of reproductive effects in r","page":16,"pdf":"out281_en.pdf","row_type":"noael_study","study_id":"out281_en_noael_002"} |
SCCS_vision_codex 20 endpoints
| Source | Endpoint Type | Value | Unit | Species | Route | Duration | Study Type | Reference |
|---|---|---|---|---|---|---|---|---|
| SCCS_vision_codex | NOAEL | =100 | mg/kg bw/day | dog | - | Chronic | NOAEL study | {"citation":"Ref.: Add ref A, B 3","dose":"Although the incidence was similar in all dose groups, the severity of this lesion was slightly increased in the high-dose group only.","effect":"epithelial cells was increased compared to controls. Although the incidence was similar in all dose groups, the severity of this lesion was slightly increased in the high-dose group only. In addition, increased incidences of necrotic tubular epithelium were seen in all treated groups compared to controls, however no dose-effect relationship either in incidence or severity was observed. The Panel, having consulted the tables in the original Japanese and the English abstract of this study, concludes that there was a NOAEL of 100 mg/kg bw/day for males and that the NOAEL for females was below 100 mg/kg bw/day (the lowest dose tested). Based on the lack of a clear dose-response relationship in this study the Panel was unable to identify a suitable NOAEL, LOAEL or Bench Mark Dose (BMD) to establish an ADI and concludes that the existing SCF ADI of 0-1.5 mg/kg bw/day should be withdrawn. Ref.: Add ref A, B 3.3.5.3. Chronic (> 12 months) toxicity Taken from SCCNFP/0795/04 Data for the calcium-salt 2-year feeding study in dogs Dietar","page":16,"pdf":"sccs_o_112.pdf","row_type":"noael_study","study_id":"sccs_o_112_noael_001"} |
| SCCS_vision_codex | NOAEL | =0 | mg/kg bw/day | dog | oral | Chronic | NOAEL study | {"citation":"Ref.: Add ref A, B 3","dose":"tubular epithelium were seen in all treated groups compared to controls, however no dose-effect relationship either in incidence or severity was observed.","effect":"tubular epithelium were seen in all treated groups compared to controls, however no dose-effect relationship either in incidence or severity was observed. The Panel, having consulted the tables in the original Japanese and the English abstract of this study, concludes that there was a NOAEL of 100 mg/kg bw/day for males and that the NOAEL for females was below 100 mg/kg bw/day (the lowest dose tested). Based on the lack of a clear dose-response relationship in this study the Panel was unable to identify a suitable NOAEL, LOAEL or Bench Mark Dose (BMD) to establish an ADI and concludes that the existing SCF ADI of 0-1.5 mg/kg bw/day should be withdrawn. Ref.: Add ref A, B 3.3.5.3. Chronic (> 12 months) toxicity Taken from SCCNFP/0795/04 Data for the calcium-salt 2-year feeding study in dogs Dietary levels of 0.015, 0.1 and 1.0 % (about 250 mg/kg bw/day) of the test substance were fed to dogs (3 animals per sex) for 2 years. A concurrent control group of 6 animals per sex was also investigated. General conditions, body weight,","page":16,"pdf":"sccs_o_112.pdf","row_type":"noael_study","study_id":"sccs_o_112_noael_003"} |
| SCCS_vision_codex | NOAEL | =150 | mg/kg bw/day | rat | - | chronic | NOAEL study | {"dose":"hologists from the US Food and Drug Administration subsequently examined tissue sections from the kidneys of all treated rats, they concluded that Lithol Rubine B exacerbated a spontaneous kidney disease of aged rats (chronic progressive nephrosis) in the mid- and high-dose males and in the high-dose females.","effect":"hologists from the US Food and Drug Administration subsequently examined tissue sections from the kidneys of all treated rats, they concluded that Lithol Rubine B exacerbated a spontaneous kidney disease of aged rats (chronic progressive nephrosis) in the mid- and high-dose males and in the high-dose females. An acceleration of testicular changes (degeneration of the testicular tubules), common in ageing rats, was also reported in high-dose males, but the increased incidence was of no statistical significance. The NOAEL was 150 mg/kg bw/day.","page":16,"pdf":"sccs_o_112.pdf","row_type":"noael_study","study_id":"sccs_o_112_noael_004"} |
| SCCS_vision_codex | NOAEL | =0.003 | mg/kg bw/d | rat | - | - | NOAEL study | {"dose":"However, the systemic exposure dose (SED) has been calculated to be 0.003 mg/kg bw/d for a typical non-oxidative hair dye formulation, which is considered very low by the SCCS and is more than 30.000 fold lower than the identified effect level of 100 mg/kg bw/day in female rats.","effect":"e was used for patch testing. The patch test dilution was high; no serial dilutions were undertaken. No control tests are reported. Purity of the test substance is not disclosed. The information does not confirm that Pigment Red 57 itself was the cause of the reaction. 3.3.12. Special investigations No data submitted 3.3.13. Safety evaluation (including calculation of the MoS) CALCULATION OF THE MARGIN OF SAFETY Pigment Red 57 Not applicable Due to the limited quality of the submitted toxicological data, a NOAEL/LOAEL cannot be derived with sufficient confidence from these studies, and therefore a MOS cannot be calculated for Pigment Red 57. However, the systemic exposure dose (SED) has been calculated to be 0.003 mg/kg bw/d for a typical non-oxidative hair dye formulation, which is considered very low by the SCCS and is more than 30.000 fold lower than the identified effect level of 100 mg/kg bw/day in female rats. Therefore, the SCCS considers that it is unlikely that there would be a safety concern for consumers from","page":25,"pdf":"sccs_o_112.pdf","row_type":"noael_study","study_id":"sccs_o_112_noael_005"} |
| SCCS_vision_codex | NOAEL | =100 | mg/kg bw/d | rat | oral | chronic | genotoxicity | {"dose":"However the LOAEL is probably around 100 mg/kg bw/d.","effect":"is of low acute toxicity in rats and dogs. Repeated and chronic oral administration to rodents showed the kidney as a primary target organ in the high doses. However, the SCCS considers that the toxicological data are for most of them not complying with current standards and not fully reported. Most of the studies provided in the dossier are indeed summaries from the BIBRA’s report from 1997. These studies have also been evaluated recently by the EFSA panel on food additives and nutrient sources added to food. No NOAEL can be derived from the submitted studies. However the LOAEL is probably around 100 mg/kg bw/d. Mutagenicity Overall, the genotoxicity of Pigment Red 57 is sufficiently investigated in valid genotoxicity tests for the 3 endpoints of genotoxicity: gene mutations, chromosome aberrations and aneuploidy. Pigment Red 57 did not induce gene mutations in bacteria either without metabolic activation or with Aroclor induced rat liver S9-mix or uninduced hamster liver S9- mix. Pigment Red 57 did not induce gene mutations","page":26,"pdf":"sccs_o_112.pdf","row_type":"noael_study","study_id":"sccs_o_112_noael_006"} |
| SCCS_vision_codex | NOAEL | =100 | mg/kg bw/day | dog | - | Chronic | NOAEL study | {"citation":"Ref.: Add ref A, B 3","dose":"Although the incidence was similar in all dose groups, the severity of this lesion was slightly increased in the high-dose group only.","effect":"epithelial cells was increased compared to controls. Although the incidence was similar in all dose groups, the severity of this lesion was slightly increased in the high-dose group only. In addition, increased incidences of necrotic tubular epithelium were seen in all treated groups compared to controls, however no dose-effect relationship either in incidence or severity was observed. The Panel, having consulted the tables in the original Japanese and the English abstract of this study, concludes that there was a NOAEL of 100 mg/kg bw/day for males and that the NOAEL for females was below 100 mg/kg bw/day (the lowest dose tested). Based on the lack of a clear dose-response relationship in this study the Panel was unable to identify a suitable NOAEL, LOAEL or Bench Mark Dose (BMD) to establish an ADI and concludes that the existing SCF ADI of 0-1.5 mg/kg bw/day should be withdrawn. Ref.: Add ref A, B 3.3.5.3. Chronic (> 12 months) toxicity Taken from SCCNFP/0795/04 Data for the calcium-salt 2-year feeding study in dogs Dietar","page":16,"pdf":"sccs_o_112.pdf","row_type":"noael_study","study_id":"sccs_o_112_noael_001"} |
| SCCS_vision_codex | NOAEL | =0 | mg/kg bw/day | dog | oral | Chronic | NOAEL study | {"citation":"Ref.: Add ref A, B 3","dose":"tubular epithelium were seen in all treated groups compared to controls, however no dose-effect relationship either in incidence or severity was observed.","effect":"tubular epithelium were seen in all treated groups compared to controls, however no dose-effect relationship either in incidence or severity was observed. The Panel, having consulted the tables in the original Japanese and the English abstract of this study, concludes that there was a NOAEL of 100 mg/kg bw/day for males and that the NOAEL for females was below 100 mg/kg bw/day (the lowest dose tested). Based on the lack of a clear dose-response relationship in this study the Panel was unable to identify a suitable NOAEL, LOAEL or Bench Mark Dose (BMD) to establish an ADI and concludes that the existing SCF ADI of 0-1.5 mg/kg bw/day should be withdrawn. Ref.: Add ref A, B 3.3.5.3. Chronic (> 12 months) toxicity Taken from SCCNFP/0795/04 Data for the calcium-salt 2-year feeding study in dogs Dietary levels of 0.015, 0.1 and 1.0 % (about 250 mg/kg bw/day) of the test substance were fed to dogs (3 animals per sex) for 2 years. A concurrent control group of 6 animals per sex was also investigated. General conditions, body weight,","page":16,"pdf":"sccs_o_112.pdf","row_type":"noael_study","study_id":"sccs_o_112_noael_003"} |
| SCCS_vision_codex | NOAEL | =150 | mg/kg bw/day | rat | - | chronic | NOAEL study | {"dose":"hologists from the US Food and Drug Administration subsequently examined tissue sections from the kidneys of all treated rats, they concluded that Lithol Rubine B exacerbated a spontaneous kidney disease of aged rats (chronic progressive nephrosis) in the mid- and high-dose males and in the high-dose females.","effect":"hologists from the US Food and Drug Administration subsequently examined tissue sections from the kidneys of all treated rats, they concluded that Lithol Rubine B exacerbated a spontaneous kidney disease of aged rats (chronic progressive nephrosis) in the mid- and high-dose males and in the high-dose females. An acceleration of testicular changes (degeneration of the testicular tubules), common in ageing rats, was also reported in high-dose males, but the increased incidence was of no statistical significance. The NOAEL was 150 mg/kg bw/day.","page":16,"pdf":"sccs_o_112.pdf","row_type":"noael_study","study_id":"sccs_o_112_noael_004"} |
| SCCS_vision_codex | NOAEL | =0.003 | mg/kg bw/d | rat | - | - | NOAEL study | {"dose":"However, the systemic exposure dose (SED) has been calculated to be 0.003 mg/kg bw/d for a typical non-oxidative hair dye formulation, which is considered very low by the SCCS and is more than 30.000 fold lower than the identified effect level of 100 mg/kg bw/day in female rats.","effect":"e was used for patch testing. The patch test dilution was high; no serial dilutions were undertaken. No control tests are reported. Purity of the test substance is not disclosed. The information does not confirm that Pigment Red 57 itself was the cause of the reaction. 3.3.12. Special investigations No data submitted 3.3.13. Safety evaluation (including calculation of the MoS) CALCULATION OF THE MARGIN OF SAFETY Pigment Red 57 Not applicable Due to the limited quality of the submitted toxicological data, a NOAEL/LOAEL cannot be derived with sufficient confidence from these studies, and therefore a MOS cannot be calculated for Pigment Red 57. However, the systemic exposure dose (SED) has been calculated to be 0.003 mg/kg bw/d for a typical non-oxidative hair dye formulation, which is considered very low by the SCCS and is more than 30.000 fold lower than the identified effect level of 100 mg/kg bw/day in female rats. Therefore, the SCCS considers that it is unlikely that there would be a safety concern for consumers from","page":25,"pdf":"sccs_o_112.pdf","row_type":"noael_study","study_id":"sccs_o_112_noael_005"} |
| SCCS_vision_codex | NOAEL | =100 | mg/kg bw/d | rat | oral | chronic | genotoxicity | {"dose":"However the LOAEL is probably around 100 mg/kg bw/d.","effect":"is of low acute toxicity in rats and dogs. Repeated and chronic oral administration to rodents showed the kidney as a primary target organ in the high doses. However, the SCCS considers that the toxicological data are for most of them not complying with current standards and not fully reported. Most of the studies provided in the dossier are indeed summaries from the BIBRA’s report from 1997. These studies have also been evaluated recently by the EFSA panel on food additives and nutrient sources added to food. No NOAEL can be derived from the submitted studies. However the LOAEL is probably around 100 mg/kg bw/d. Mutagenicity Overall, the genotoxicity of Pigment Red 57 is sufficiently investigated in valid genotoxicity tests for the 3 endpoints of genotoxicity: gene mutations, chromosome aberrations and aneuploidy. Pigment Red 57 did not induce gene mutations in bacteria either without metabolic activation or with Aroclor induced rat liver S9-mix or uninduced hamster liver S9- mix. Pigment Red 57 did not induce gene mutations","page":26,"pdf":"sccs_o_112.pdf","row_type":"noael_study","study_id":"sccs_o_112_noael_006"} |
| SCCS_vision_codex | NOAEL | =100 | mg/kg bw/day | dog | - | Chronic | NOAEL study | {"citation":"Ref.: Add ref A, B 3","dose":"Although the incidence was similar in all dose groups, the severity of this lesion was slightly increased in the high-dose group only.","effect":"epithelial cells was increased compared to controls. Although the incidence was similar in all dose groups, the severity of this lesion was slightly increased in the high-dose group only. In addition, increased incidences of necrotic tubular epithelium were seen in all treated groups compared to controls, however no dose-effect relationship either in incidence or severity was observed. The Panel, having consulted the tables in the original Japanese and the English abstract of this study, concludes that there was a NOAEL of 100 mg/kg bw/day for males and that the NOAEL for females was below 100 mg/kg bw/day (the lowest dose tested). Based on the lack of a clear dose-response relationship in this study the Panel was unable to identify a suitable NOAEL, LOAEL or Bench Mark Dose (BMD) to establish an ADI and concludes that the existing SCF ADI of 0-1.5 mg/kg bw/day should be withdrawn. Ref.: Add ref A, B 3.3.5.3. Chronic (> 12 months) toxicity Taken from SCCNFP/0795/04 Data for the calcium-salt 2-year feeding study in dogs Dietar","page":16,"pdf":"sccs_o_112.pdf","row_type":"noael_study","study_id":"sccs_o_112_noael_001"} |
| SCCS_vision_codex | NOAEL | =0 | mg/kg bw/day | dog | oral | Chronic | NOAEL study | {"citation":"Ref.: Add ref A, B 3","dose":"tubular epithelium were seen in all treated groups compared to controls, however no dose-effect relationship either in incidence or severity was observed.","effect":"tubular epithelium were seen in all treated groups compared to controls, however no dose-effect relationship either in incidence or severity was observed. The Panel, having consulted the tables in the original Japanese and the English abstract of this study, concludes that there was a NOAEL of 100 mg/kg bw/day for males and that the NOAEL for females was below 100 mg/kg bw/day (the lowest dose tested). Based on the lack of a clear dose-response relationship in this study the Panel was unable to identify a suitable NOAEL, LOAEL or Bench Mark Dose (BMD) to establish an ADI and concludes that the existing SCF ADI of 0-1.5 mg/kg bw/day should be withdrawn. Ref.: Add ref A, B 3.3.5.3. Chronic (> 12 months) toxicity Taken from SCCNFP/0795/04 Data for the calcium-salt 2-year feeding study in dogs Dietary levels of 0.015, 0.1 and 1.0 % (about 250 mg/kg bw/day) of the test substance were fed to dogs (3 animals per sex) for 2 years. A concurrent control group of 6 animals per sex was also investigated. General conditions, body weight,","page":16,"pdf":"sccs_o_112.pdf","row_type":"noael_study","study_id":"sccs_o_112_noael_003"} |
| SCCS_vision_codex | NOAEL | =150 | mg/kg bw/day | rat | - | chronic | NOAEL study | {"dose":"hologists from the US Food and Drug Administration subsequently examined tissue sections from the kidneys of all treated rats, they concluded that Lithol Rubine B exacerbated a spontaneous kidney disease of aged rats (chronic progressive nephrosis) in the mid- and high-dose males and in the high-dose females.","effect":"hologists from the US Food and Drug Administration subsequently examined tissue sections from the kidneys of all treated rats, they concluded that Lithol Rubine B exacerbated a spontaneous kidney disease of aged rats (chronic progressive nephrosis) in the mid- and high-dose males and in the high-dose females. An acceleration of testicular changes (degeneration of the testicular tubules), common in ageing rats, was also reported in high-dose males, but the increased incidence was of no statistical significance. The NOAEL was 150 mg/kg bw/day.","page":16,"pdf":"sccs_o_112.pdf","row_type":"noael_study","study_id":"sccs_o_112_noael_004"} |
| SCCS_vision_codex | NOAEL | =0.003 | mg/kg bw/d | rat | - | - | NOAEL study | {"dose":"However, the systemic exposure dose (SED) has been calculated to be 0.003 mg/kg bw/d for a typical non-oxidative hair dye formulation, which is considered very low by the SCCS and is more than 30.000 fold lower than the identified effect level of 100 mg/kg bw/day in female rats.","effect":"e was used for patch testing. The patch test dilution was high; no serial dilutions were undertaken. No control tests are reported. Purity of the test substance is not disclosed. The information does not confirm that Pigment Red 57 itself was the cause of the reaction. 3.3.12. Special investigations No data submitted 3.3.13. Safety evaluation (including calculation of the MoS) CALCULATION OF THE MARGIN OF SAFETY Pigment Red 57 Not applicable Due to the limited quality of the submitted toxicological data, a NOAEL/LOAEL cannot be derived with sufficient confidence from these studies, and therefore a MOS cannot be calculated for Pigment Red 57. However, the systemic exposure dose (SED) has been calculated to be 0.003 mg/kg bw/d for a typical non-oxidative hair dye formulation, which is considered very low by the SCCS and is more than 30.000 fold lower than the identified effect level of 100 mg/kg bw/day in female rats. Therefore, the SCCS considers that it is unlikely that there would be a safety concern for consumers from","page":25,"pdf":"sccs_o_112.pdf","row_type":"noael_study","study_id":"sccs_o_112_noael_005"} |
| SCCS_vision_codex | NOAEL | =100 | mg/kg bw/d | rat | oral | chronic | genotoxicity | {"dose":"However the LOAEL is probably around 100 mg/kg bw/d.","effect":"is of low acute toxicity in rats and dogs. Repeated and chronic oral administration to rodents showed the kidney as a primary target organ in the high doses. However, the SCCS considers that the toxicological data are for most of them not complying with current standards and not fully reported. Most of the studies provided in the dossier are indeed summaries from the BIBRA’s report from 1997. These studies have also been evaluated recently by the EFSA panel on food additives and nutrient sources added to food. No NOAEL can be derived from the submitted studies. However the LOAEL is probably around 100 mg/kg bw/d. Mutagenicity Overall, the genotoxicity of Pigment Red 57 is sufficiently investigated in valid genotoxicity tests for the 3 endpoints of genotoxicity: gene mutations, chromosome aberrations and aneuploidy. Pigment Red 57 did not induce gene mutations in bacteria either without metabolic activation or with Aroclor induced rat liver S9-mix or uninduced hamster liver S9- mix. Pigment Red 57 did not induce gene mutations","page":26,"pdf":"sccs_o_112.pdf","row_type":"noael_study","study_id":"sccs_o_112_noael_006"} |
| SCCS_vision_codex | NOAEL | =100 | mg/kg bw/day | dog | - | Chronic | NOAEL study | {"citation":"Ref.: Add ref A, B 3","dose":"Although the incidence was similar in all dose groups, the severity of this lesion was slightly increased in the high-dose group only.","effect":"epithelial cells was increased compared to controls. Although the incidence was similar in all dose groups, the severity of this lesion was slightly increased in the high-dose group only. In addition, increased incidences of necrotic tubular epithelium were seen in all treated groups compared to controls, however no dose-effect relationship either in incidence or severity was observed. The Panel, having consulted the tables in the original Japanese and the English abstract of this study, concludes that there was a NOAEL of 100 mg/kg bw/day for males and that the NOAEL for females was below 100 mg/kg bw/day (the lowest dose tested). Based on the lack of a clear dose-response relationship in this study the Panel was unable to identify a suitable NOAEL, LOAEL or Bench Mark Dose (BMD) to establish an ADI and concludes that the existing SCF ADI of 0-1.5 mg/kg bw/day should be withdrawn. Ref.: Add ref A, B 3.3.5.3. Chronic (> 12 months) toxicity Taken from SCCNFP/0795/04 Data for the calcium-salt 2-year feeding study in dogs Dietar","page":16,"pdf":"sccs_o_112.pdf","row_type":"noael_study","study_id":"sccs_o_112_noael_001"} |
| SCCS_vision_codex | NOAEL | =0 | mg/kg bw/day | dog | oral | Chronic | NOAEL study | {"citation":"Ref.: Add ref A, B 3","dose":"tubular epithelium were seen in all treated groups compared to controls, however no dose-effect relationship either in incidence or severity was observed.","effect":"tubular epithelium were seen in all treated groups compared to controls, however no dose-effect relationship either in incidence or severity was observed. The Panel, having consulted the tables in the original Japanese and the English abstract of this study, concludes that there was a NOAEL of 100 mg/kg bw/day for males and that the NOAEL for females was below 100 mg/kg bw/day (the lowest dose tested). Based on the lack of a clear dose-response relationship in this study the Panel was unable to identify a suitable NOAEL, LOAEL or Bench Mark Dose (BMD) to establish an ADI and concludes that the existing SCF ADI of 0-1.5 mg/kg bw/day should be withdrawn. Ref.: Add ref A, B 3.3.5.3. Chronic (> 12 months) toxicity Taken from SCCNFP/0795/04 Data for the calcium-salt 2-year feeding study in dogs Dietary levels of 0.015, 0.1 and 1.0 % (about 250 mg/kg bw/day) of the test substance were fed to dogs (3 animals per sex) for 2 years. A concurrent control group of 6 animals per sex was also investigated. General conditions, body weight,","page":16,"pdf":"sccs_o_112.pdf","row_type":"noael_study","study_id":"sccs_o_112_noael_003"} |
| SCCS_vision_codex | NOAEL | =150 | mg/kg bw/day | rat | - | chronic | NOAEL study | {"dose":"hologists from the US Food and Drug Administration subsequently examined tissue sections from the kidneys of all treated rats, they concluded that Lithol Rubine B exacerbated a spontaneous kidney disease of aged rats (chronic progressive nephrosis) in the mid- and high-dose males and in the high-dose females.","effect":"hologists from the US Food and Drug Administration subsequently examined tissue sections from the kidneys of all treated rats, they concluded that Lithol Rubine B exacerbated a spontaneous kidney disease of aged rats (chronic progressive nephrosis) in the mid- and high-dose males and in the high-dose females. An acceleration of testicular changes (degeneration of the testicular tubules), common in ageing rats, was also reported in high-dose males, but the increased incidence was of no statistical significance. The NOAEL was 150 mg/kg bw/day.","page":16,"pdf":"sccs_o_112.pdf","row_type":"noael_study","study_id":"sccs_o_112_noael_004"} |
| SCCS_vision_codex | NOAEL | =0.003 | mg/kg bw/d | rat | - | - | NOAEL study | {"dose":"However, the systemic exposure dose (SED) has been calculated to be 0.003 mg/kg bw/d for a typical non-oxidative hair dye formulation, which is considered very low by the SCCS and is more than 30.000 fold lower than the identified effect level of 100 mg/kg bw/day in female rats.","effect":"e was used for patch testing. The patch test dilution was high; no serial dilutions were undertaken. No control tests are reported. Purity of the test substance is not disclosed. The information does not confirm that Pigment Red 57 itself was the cause of the reaction. 3.3.12. Special investigations No data submitted 3.3.13. Safety evaluation (including calculation of the MoS) CALCULATION OF THE MARGIN OF SAFETY Pigment Red 57 Not applicable Due to the limited quality of the submitted toxicological data, a NOAEL/LOAEL cannot be derived with sufficient confidence from these studies, and therefore a MOS cannot be calculated for Pigment Red 57. However, the systemic exposure dose (SED) has been calculated to be 0.003 mg/kg bw/d for a typical non-oxidative hair dye formulation, which is considered very low by the SCCS and is more than 30.000 fold lower than the identified effect level of 100 mg/kg bw/day in female rats. Therefore, the SCCS considers that it is unlikely that there would be a safety concern for consumers from","page":25,"pdf":"sccs_o_112.pdf","row_type":"noael_study","study_id":"sccs_o_112_noael_005"} |
| SCCS_vision_codex | NOAEL | =100 | mg/kg bw/d | rat | oral | chronic | genotoxicity | {"dose":"However the LOAEL is probably around 100 mg/kg bw/d.","effect":"is of low acute toxicity in rats and dogs. Repeated and chronic oral administration to rodents showed the kidney as a primary target organ in the high doses. However, the SCCS considers that the toxicological data are for most of them not complying with current standards and not fully reported. Most of the studies provided in the dossier are indeed summaries from the BIBRA’s report from 1997. These studies have also been evaluated recently by the EFSA panel on food additives and nutrient sources added to food. No NOAEL can be derived from the submitted studies. However the LOAEL is probably around 100 mg/kg bw/d. Mutagenicity Overall, the genotoxicity of Pigment Red 57 is sufficiently investigated in valid genotoxicity tests for the 3 endpoints of genotoxicity: gene mutations, chromosome aberrations and aneuploidy. Pigment Red 57 did not induce gene mutations in bacteria either without metabolic activation or with Aroclor induced rat liver S9-mix or uninduced hamster liver S9- mix. Pigment Red 57 did not induce gene mutations","page":26,"pdf":"sccs_o_112.pdf","row_type":"noael_study","study_id":"sccs_o_112_noael_006"} |
UnifiedCodex:SCCNFP:beta.noael_studies 2 endpoints
| Source | Endpoint Type | Value | Unit | Species | Route | Duration | Study Type | Reference |
|---|---|---|---|---|---|---|---|---|
| UnifiedCodex:SCCNFP:beta.noael_studies | - | 150 | mg/kg bw/day | rat | oral | chronic | - | SOURCE_SUBDIR=out281_en; REPORT_TITLE=OPINION OF THE SCIENTIFIC COMMITTEE ON COSMETIC PRODUCTS AND NON-FOOD PRODUCTS INTENDED FOR CONSUMERS CONCERNING PIGMENT RED 57 COLIPA n° : /; OPINION_NUMBER=SCCNFP/0795/04; COMMITTEE=SCCNFP; REPORT_DATE=25 May 2004; VALUE_TEXT=150; DOSE=hologists from the US Food and Drug Administration subsequently examined tissue sections from the kidneys of all treated rats, they concluded that Lithol Rubine B exacerbated a spontaneous kidney disease of aged rats (chronic progressive nephrosis) in the mid- and high-dose males and in the high-dose females.; EFFECT=hologists from the US Food and Drug Administration subsequently examined tissue sections from the kidneys of all treated rats, they concluded that Lithol Rubine B exacerbated a spontaneous kidney disease of aged rats (chronic progressive nephrosis) in the mid- and high-dose males and in the high-dose females. An acceleration of testicular changes (degeneration of the testicular tubules), common in ageing rats, was also reported in high-dose males, but the increased incidence was of no statistical significance. The NOAEL was 150 mg/kg bw/day. Ref.: 2 Chronic oral toxicity study in mice Groups of 60 males and 60 females that were exposed to concentrations of 0.05, 1 or 5 % Pigment Red 57 in their diet (approximately 75, 1500 or 7500 mg/kg bw/day, respectively) for 2 years, showed no changes in food consumption, body weight gain, or blood composition. At the end of the study, the weights of the brain, kidneys, liver and spleen were unaffected and there were no abnormalities evident on gross examination. The treated males showed inc; CITATION=Ref.: 2 Chronic oral toxicity study in mice Groups of 60 males and 60 females that were exposed to concentrations of 0; CITATION_NUMBERS=[2,60]; REFERENCE=Ref.: 2 Chronic oral toxicity study in mice Groups of 60 males and 60 females that were exposed to concentrations of 0; DETAILS_JSON={"cas_number":"5858-81-1","citation":"Ref.: 2 Chronic oral toxicity study in mice Groups of 60 males and 60 females that were exposed to concentrations of 0","dose":"hologists from the US Food and Drug Administration subsequently examined tissue sections from the kidneys of all treated rats, they concluded that Lithol Rubine B exacerbated a spontaneous kidney disease of aged rats (chronic progressive nephrosis) in the mid- and high-dose males and in the high-dose females.","duration":"chronic","effect":"hologists from the US Food and Drug Administration subsequently examined tissue sections from the kidneys of all treated rats, they concluded that Lithol Rubine B exacerbated a spontaneous kidney disease of aged rats (chronic progressive nephrosis) in the mid- and high-dose males and in the high-dose females. An acceleration of testicular changes (degeneration of the testicular tubules), common in ageing rats, was also reported in high-dose males, but the increased incidence was of no statistical significance. The NOAEL was 150 mg/kg bw/day. Ref.: 2 Chronic oral toxicity study in mice Groups of 60 males and 60 females that were exposed to concentrations of 0.05, 1 or 5 % Pigment Red 57 in their diet (approximately 75, 1500 or 7500 mg/kg bw/day, respectively) for 2 years, showed no changes in food consumption, body weight gain, or blood composition. At the end of the study, the weights of the brain, kidneys, liver and spleen were unaffected and there were no abnormalities evident on gross examination. The treated males showed inc","endpoint":"","ingredient":"codes","loael_value":"","noael_unit":"mg/kg bw/day","noael_value":"150","page":8,"route":"oral","species":"rat","study_id":"out281_en_noael_001"} |
| UnifiedCodex:SCCNFP:beta.noael_studies | reproductive toxicity | 150 | mg/kg | rat | oral | 18 months | reproductive toxicity | SOURCE_SUBDIR=out281_en; REPORT_TITLE=OPINION OF THE SCIENTIFIC COMMITTEE ON COSMETIC PRODUCTS AND NON-FOOD PRODUCTS INTENDED FOR CONSUMERS CONCERNING PIGMENT RED 57 COLIPA n° : /; OPINION_NUMBER=SCCNFP/0795/04; COMMITTEE=SCCNFP; REPORT_DATE=25 May 2004; VALUE_TEXT=150; DOSE=ed 57 (calcium salt) (about 50 mg/kg bw/application) for 18 months.; EFFECT=ed 57 (calcium salt) (about 50 mg/kg bw/application) for 18 months. Tissues from the skin were microscopically examined, as were other tissues that appeared abnormal on gross examination. Ref.: 3 2.10. Special investigations No data 2.11. Safety evaluation Not applicable 2.12. Conclusions Pigment Red 57 (Lithol Rubine B and BK) is of low acute toxicity in rats and dogs. Repeated and chronic oral administration to rodents up to 2 years, showed the kidney as a primary target organ in the high doses. The lowest NOAEL (150 mg/kg/bw/day) was obtained in the 2 years toxicity study in rats performed with the F1-generation of parent-animals pretreated at the same dose levels. The SCF also used this study to derive an ADI for this compound. There is no indication for corrosivity or comedogenic effects on the skin. Also no irritation on mucous membranes was noted. From the results of the local lymph node assay it is concluded that Pigment Red 57 is not a skin-sensitiser. There was no convincing evidence of reproductive effects in r; CITATION=Ref.: 3 2; CITATION_NUMBERS=[3,2]; REFERENCE=Ref.: 3 2; DETAILS_JSON={"cas_number":"5858-81-1","citation":"Ref.: 3 2","dose":"ed 57 (calcium salt) (about 50 mg/kg bw/application) for 18 months.","duration":"18 months","effect":"ed 57 (calcium salt) (about 50 mg/kg bw/application) for 18 months. Tissues from the skin were microscopically examined, as were other tissues that appeared abnormal on gross examination. Ref.: 3 2.10. Special investigations No data 2.11. Safety evaluation Not applicable 2.12. Conclusions Pigment Red 57 (Lithol Rubine B and BK) is of low acute toxicity in rats and dogs. Repeated and chronic oral administration to rodents up to 2 years, showed the kidney as a primary target organ in the high doses. The lowest NOAEL (150 mg/kg/bw/day) was obtained in the 2 years toxicity study in rats performed with the F1-generation of parent-animals pretreated at the same dose levels. The SCF also used this study to derive an ADI for this compound. There is no indication for corrosivity or comedogenic effects on the skin. Also no irritation on mucous membranes was noted. From the results of the local lymph node assay it is concluded that Pigment Red 57 is not a skin-sensitiser. There was no convincing evidence of reproductive effects in r","endpoint":"reproductive toxicity","ingredient":"codes","loael_value":"","noael_unit":"mg/kg","noael_value":"150","page":16,"route":"oral","species":"rat","study_id":"out281_en_noael_002"} |
UnifiedCodex:SCCS_SHADOW:beta.noael_studies 6 endpoints
| Source | Endpoint Type | Value | Unit | Species | Route | Duration | Study Type | Reference |
|---|---|---|---|---|---|---|---|---|
| UnifiedCodex:SCCS_SHADOW:beta.noael_studies | - | 100 | mg/kg bw/day | dog | - | Chronic | - | SOURCE_SUBDIR=sccs_o_112; REPORT_TITLE=OPINION ON Pigment Red 57 COLIPA n° C181; OPINION_NUMBER=SCCS/1411/11; COMMITTEE=Scientific Committee on Consumer Safety (SCCS); REPORT_DATE=11 December 2012; VALUE_TEXT=100; DOSE=Although the incidence was similar in all dose groups, the severity of this lesion was slightly increased in the high-dose group only.; LOAEL_VALUE=1.5 mg/kg bw/day; EFFECT=epithelial cells was increased compared to controls. Although the incidence was similar in all dose groups, the severity of this lesion was slightly increased in the high-dose group only. In addition, increased incidences of necrotic tubular epithelium were seen in all treated groups compared to controls, however no dose-effect relationship either in incidence or severity was observed. The Panel, having consulted the tables in the original Japanese and the English abstract of this study, concludes that there was a NOAEL of 100 mg/kg bw/day for males and that the NOAEL for females was below 100 mg/kg bw/day (the lowest dose tested). Based on the lack of a clear dose-response relationship in this study the Panel was unable to identify a suitable NOAEL, LOAEL or Bench Mark Dose (BMD) to establish an ADI and concludes that the existing SCF ADI of 0-1.5 mg/kg bw/day should be withdrawn. Ref.: Add ref A, B 3.3.5.3. Chronic (> 12 months) toxicity Taken from SCCNFP/0795/04 Data for the calcium-salt 2-year feeding study in dogs Dietar; CITATION=Ref.: Add ref A, B 3; CITATION_NUMBERS=[3]; REFERENCE=Ref.: Add ref A, B 3; DETAILS_JSON={"cas_number":"5858-81-1","citation":"Ref.: Add ref A, B 3","dose":"Although the incidence was similar in all dose groups, the severity of this lesion was slightly increased in the high-dose group only.","duration":"Chronic","effect":"epithelial cells was increased compared to controls. Although the incidence was similar in all dose groups, the severity of this lesion was slightly increased in the high-dose group only. In addition, increased incidences of necrotic tubular epithelium were seen in all treated groups compared to controls, however no dose-effect relationship either in incidence or severity was observed. The Panel, having consulted the tables in the original Japanese and the English abstract of this study, concludes that there was a NOAEL of 100 mg/kg bw/day for males and that the NOAEL for females was below 100 mg/kg bw/day (the lowest dose tested). Based on the lack of a clear dose-response relationship in this study the Panel was unable to identify a suitable NOAEL, LOAEL or Bench Mark Dose (BMD) to establish an ADI and concludes that the existing SCF ADI of 0-1.5 mg/kg bw/day should be withdrawn. Ref.: Add ref A, B 3.3.5.3. Chronic (> 12 months) toxicity Taken from SCCNFP/0795/04 Data for the calcium-salt 2-year feeding study in dogs Dietar","endpoint":"","ingredient":"Pigment Red 57","loael_value":"1.5 mg/kg bw/day","noael_unit":"mg/kg bw/day","noael_value":"100","page":16,"route":"","species":"dog","study_id":"sccs_o_112_noael_001"} |
| UnifiedCodex:SCCS_SHADOW:beta.noael_studies | - | 100 | mg/kg bw/day | dog | oral | Chronic | - | SOURCE_SUBDIR=sccs_o_112; REPORT_TITLE=OPINION ON Pigment Red 57 COLIPA n° C181; OPINION_NUMBER=SCCS/1411/11; COMMITTEE=Scientific Committee on Consumer Safety (SCCS); REPORT_DATE=11 December 2012; VALUE_TEXT=100; DOSE=Although the incidence was similar in all dose groups, the severity of this lesion was slightly increased in the high-dose group only.; LOAEL_VALUE=1.5 mg/kg bw/day; EFFECT=ls. Although the incidence was similar in all dose groups, the severity of this lesion was slightly increased in the high-dose group only. In addition, increased incidences of necrotic tubular epithelium were seen in all treated groups compared to controls, however no dose-effect relationship either in incidence or severity was observed. The Panel, having consulted the tables in the original Japanese and the English abstract of this study, concludes that there was a NOAEL of 100 mg/kg bw/day for males and that the NOAEL for females was below 100 mg/kg bw/day (the lowest dose tested). Based on the lack of a clear dose-response relationship in this study the Panel was unable to identify a suitable NOAEL, LOAEL or Bench Mark Dose (BMD) to establish an ADI and concludes that the existing SCF ADI of 0-1.5 mg/kg bw/day should be withdrawn. Ref.: Add ref A, B 3.3.5.3. Chronic (> 12 months) toxicity Taken from SCCNFP/0795/04 Data for the calcium-salt 2-year feeding study in dogs Dietary levels of 0.015, 0.1 and 1.0 % (about 250 mg/kg; CITATION=Ref.: Add ref A, B 3; CITATION_NUMBERS=[3]; REFERENCE=Ref.: Add ref A, B 3; DETAILS_JSON={"cas_number":"5858-81-1","citation":"Ref.: Add ref A, B 3","dose":"Although the incidence was similar in all dose groups, the severity of this lesion was slightly increased in the high-dose group only.","duration":"Chronic","effect":"ls. Although the incidence was similar in all dose groups, the severity of this lesion was slightly increased in the high-dose group only. In addition, increased incidences of necrotic tubular epithelium were seen in all treated groups compared to controls, however no dose-effect relationship either in incidence or severity was observed. The Panel, having consulted the tables in the original Japanese and the English abstract of this study, concludes that there was a NOAEL of 100 mg/kg bw/day for males and that the NOAEL for females was below 100 mg/kg bw/day (the lowest dose tested). Based on the lack of a clear dose-response relationship in this study the Panel was unable to identify a suitable NOAEL, LOAEL or Bench Mark Dose (BMD) to establish an ADI and concludes that the existing SCF ADI of 0-1.5 mg/kg bw/day should be withdrawn. Ref.: Add ref A, B 3.3.5.3. Chronic (> 12 months) toxicity Taken from SCCNFP/0795/04 Data for the calcium-salt 2-year feeding study in dogs Dietary levels of 0.015, 0.1 and 1.0 % (about 250 mg/kg","endpoint":"","ingredient":"Pigment Red 57","loael_value":"1.5 mg/kg bw/day","noael_unit":"mg/kg bw/day","noael_value":"100","page":16,"route":"oral","species":"dog","study_id":"sccs_o_112_noael_002"} |
| UnifiedCodex:SCCS_SHADOW:beta.noael_studies | - | 0 | mg/kg bw/day | dog | oral | Chronic | - | SOURCE_SUBDIR=sccs_o_112; REPORT_TITLE=OPINION ON Pigment Red 57 COLIPA n° C181; OPINION_NUMBER=SCCS/1411/11; COMMITTEE=Scientific Committee on Consumer Safety (SCCS); REPORT_DATE=11 December 2012; VALUE_TEXT=0-1.5; DOSE=tubular epithelium were seen in all treated groups compared to controls, however no dose-effect relationship either in incidence or severity was observed.; LOAEL_VALUE=1.5 mg/kg bw/day; EFFECT=tubular epithelium were seen in all treated groups compared to controls, however no dose-effect relationship either in incidence or severity was observed. The Panel, having consulted the tables in the original Japanese and the English abstract of this study, concludes that there was a NOAEL of 100 mg/kg bw/day for males and that the NOAEL for females was below 100 mg/kg bw/day (the lowest dose tested). Based on the lack of a clear dose-response relationship in this study the Panel was unable to identify a suitable NOAEL, LOAEL or Bench Mark Dose (BMD) to establish an ADI and concludes that the existing SCF ADI of 0-1.5 mg/kg bw/day should be withdrawn. Ref.: Add ref A, B 3.3.5.3. Chronic (> 12 months) toxicity Taken from SCCNFP/0795/04 Data for the calcium-salt 2-year feeding study in dogs Dietary levels of 0.015, 0.1 and 1.0 % (about 250 mg/kg bw/day) of the test substance were fed to dogs (3 animals per sex) for 2 years. A concurrent control group of 6 animals per sex was also investigated. General conditions, body weight,; CITATION=Ref.: Add ref A, B 3; CITATION_NUMBERS=[3]; REFERENCE=Ref.: Add ref A, B 3; DETAILS_JSON={"cas_number":"5858-81-1","citation":"Ref.: Add ref A, B 3","dose":"tubular epithelium were seen in all treated groups compared to controls, however no dose-effect relationship either in incidence or severity was observed.","duration":"Chronic","effect":"tubular epithelium were seen in all treated groups compared to controls, however no dose-effect relationship either in incidence or severity was observed. The Panel, having consulted the tables in the original Japanese and the English abstract of this study, concludes that there was a NOAEL of 100 mg/kg bw/day for males and that the NOAEL for females was below 100 mg/kg bw/day (the lowest dose tested). Based on the lack of a clear dose-response relationship in this study the Panel was unable to identify a suitable NOAEL, LOAEL or Bench Mark Dose (BMD) to establish an ADI and concludes that the existing SCF ADI of 0-1.5 mg/kg bw/day should be withdrawn. Ref.: Add ref A, B 3.3.5.3. Chronic (> 12 months) toxicity Taken from SCCNFP/0795/04 Data for the calcium-salt 2-year feeding study in dogs Dietary levels of 0.015, 0.1 and 1.0 % (about 250 mg/kg bw/day) of the test substance were fed to dogs (3 animals per sex) for 2 years. A concurrent control group of 6 animals per sex was also investigated. General conditions, body weight,","endpoint":"","ingredient":"Pigment Red 57","loael_value":"1.5 mg/kg bw/day","noael_unit":"mg/kg bw/day","noael_value":"0-1.5","page":16,"route":"oral","species":"dog","study_id":"sccs_o_112_noael_003"} |
| UnifiedCodex:SCCS_SHADOW:beta.noael_studies | - | 150 | mg/kg bw/day | rat | - | chronic | - | SOURCE_SUBDIR=sccs_o_112; REPORT_TITLE=OPINION ON Pigment Red 57 COLIPA n° C181; OPINION_NUMBER=SCCS/1411/11; COMMITTEE=Scientific Committee on Consumer Safety (SCCS); REPORT_DATE=11 December 2012; VALUE_TEXT=150; DOSE=hologists from the US Food and Drug Administration subsequently examined tissue sections from the kidneys of all treated rats, they concluded that Lithol Rubine B exacerbated a spontaneous kidney disease of aged rats (chronic progressive nephrosis) in the mid- and high-dose males and in the high-dose females.; EFFECT=hologists from the US Food and Drug Administration subsequently examined tissue sections from the kidneys of all treated rats, they concluded that Lithol Rubine B exacerbated a spontaneous kidney disease of aged rats (chronic progressive nephrosis) in the mid- and high-dose males and in the high-dose females. An acceleration of testicular changes (degeneration of the testicular tubules), common in ageing rats, was also reported in high-dose males, but the increased incidence was of no statistical significance. The NOAEL was 150 mg/kg bw/day.; CITATION_NUMBERS=[]; DETAILS_JSON={"cas_number":"5858-81-1","citation":"","dose":"hologists from the US Food and Drug Administration subsequently examined tissue sections from the kidneys of all treated rats, they concluded that Lithol Rubine B exacerbated a spontaneous kidney disease of aged rats (chronic progressive nephrosis) in the mid- and high-dose males and in the high-dose females.","duration":"chronic","effect":"hologists from the US Food and Drug Administration subsequently examined tissue sections from the kidneys of all treated rats, they concluded that Lithol Rubine B exacerbated a spontaneous kidney disease of aged rats (chronic progressive nephrosis) in the mid- and high-dose males and in the high-dose females. An acceleration of testicular changes (degeneration of the testicular tubules), common in ageing rats, was also reported in high-dose males, but the increased incidence was of no statistical significance. The NOAEL was 150 mg/kg bw/day.","endpoint":"","ingredient":"Pigment Red 57","loael_value":"","noael_unit":"mg/kg bw/day","noael_value":"150","page":16,"route":"","species":"rat","study_id":"sccs_o_112_noael_004"} |
| UnifiedCodex:SCCS_SHADOW:beta.noael_studies | - | 0.003 | mg/kg bw/d | rat | - | - | - | SOURCE_SUBDIR=sccs_o_112; REPORT_TITLE=OPINION ON Pigment Red 57 COLIPA n° C181; OPINION_NUMBER=SCCS/1411/11; COMMITTEE=Scientific Committee on Consumer Safety (SCCS); REPORT_DATE=11 December 2012; VALUE_TEXT=0.003; DOSE=However, the systemic exposure dose (SED) has been calculated to be 0.003 mg/kg bw/d for a typical non-oxidative hair dye formulation, which is considered very low by the SCCS and is more than 30.000 fold lower than the identified effect level of 100 mg/kg bw/day in female rats.; EFFECT=e was used for patch testing. The patch test dilution was high; no serial dilutions were undertaken. No control tests are reported. Purity of the test substance is not disclosed. The information does not confirm that Pigment Red 57 itself was the cause of the reaction. 3.3.12. Special investigations No data submitted 3.3.13. Safety evaluation (including calculation of the MoS) CALCULATION OF THE MARGIN OF SAFETY Pigment Red 57 Not applicable Due to the limited quality of the submitted toxicological data, a NOAEL/LOAEL cannot be derived with sufficient confidence from these studies, and therefore a MOS cannot be calculated for Pigment Red 57. However, the systemic exposure dose (SED) has been calculated to be 0.003 mg/kg bw/d for a typical non-oxidative hair dye formulation, which is considered very low by the SCCS and is more than 30.000 fold lower than the identified effect level of 100 mg/kg bw/day in female rats. Therefore, the SCCS considers that it is unlikely that there would be a safety concern for consumers from; CITATION_NUMBERS=[]; DETAILS_JSON={"cas_number":"5858-81-1","citation":"","dose":"However, the systemic exposure dose (SED) has been calculated to be 0.003 mg/kg bw/d for a typical non-oxidative hair dye formulation, which is considered very low by the SCCS and is more than 30.000 fold lower than the identified effect level of 100 mg/kg bw/day in female rats.","duration":"","effect":"e was used for patch testing. The patch test dilution was high; no serial dilutions were undertaken. No control tests are reported. Purity of the test substance is not disclosed. The information does not confirm that Pigment Red 57 itself was the cause of the reaction. 3.3.12. Special investigations No data submitted 3.3.13. Safety evaluation (including calculation of the MoS) CALCULATION OF THE MARGIN OF SAFETY Pigment Red 57 Not applicable Due to the limited quality of the submitted toxicological data, a NOAEL/LOAEL cannot be derived with sufficient confidence from these studies, and therefore a MOS cannot be calculated for Pigment Red 57. However, the systemic exposure dose (SED) has been calculated to be 0.003 mg/kg bw/d for a typical non-oxidative hair dye formulation, which is considered very low by the SCCS and is more than 30.000 fold lower than the identified effect level of 100 mg/kg bw/day in female rats. Therefore, the SCCS considers that it is unlikely that there would be a safety concern for consumers from","endpoint":"","ingredient":"Pigment Red 57","loael_value":"","noael_unit":"mg/kg bw/d","noael_value":"0.003","page":25,"route":"","species":"rat","study_id":"sccs_o_112_noael_005"} |
| UnifiedCodex:SCCS_SHADOW:beta.noael_studies | genotoxicity | 100 | mg/kg bw/d | rat | oral | chronic | genotoxicity | SOURCE_SUBDIR=sccs_o_112; REPORT_TITLE=OPINION ON Pigment Red 57 COLIPA n° C181; OPINION_NUMBER=SCCS/1411/11; COMMITTEE=Scientific Committee on Consumer Safety (SCCS); REPORT_DATE=11 December 2012; VALUE_TEXT=100; DOSE=However the LOAEL is probably around 100 mg/kg bw/d.; LOAEL_VALUE=100 mg/kg bw/d; EFFECT=is of low acute toxicity in rats and dogs. Repeated and chronic oral administration to rodents showed the kidney as a primary target organ in the high doses. However, the SCCS considers that the toxicological data are for most of them not complying with current standards and not fully reported. Most of the studies provided in the dossier are indeed summaries from the BIBRA’s report from 1997. These studies have also been evaluated recently by the EFSA panel on food additives and nutrient sources added to food. No NOAEL can be derived from the submitted studies. However the LOAEL is probably around 100 mg/kg bw/d. Mutagenicity Overall, the genotoxicity of Pigment Red 57 is sufficiently investigated in valid genotoxicity tests for the 3 endpoints of genotoxicity: gene mutations, chromosome aberrations and aneuploidy. Pigment Red 57 did not induce gene mutations in bacteria either without metabolic activation or with Aroclor induced rat liver S9-mix or uninduced hamster liver S9- mix. Pigment Red 57 did not induce gene mutations; CITATION_NUMBERS=[]; DETAILS_JSON={"cas_number":"5858-81-1","citation":"","dose":"However the LOAEL is probably around 100 mg/kg bw/d.","duration":"chronic","effect":"is of low acute toxicity in rats and dogs. Repeated and chronic oral administration to rodents showed the kidney as a primary target organ in the high doses. However, the SCCS considers that the toxicological data are for most of them not complying with current standards and not fully reported. Most of the studies provided in the dossier are indeed summaries from the BIBRA’s report from 1997. These studies have also been evaluated recently by the EFSA panel on food additives and nutrient sources added to food. No NOAEL can be derived from the submitted studies. However the LOAEL is probably around 100 mg/kg bw/d. Mutagenicity Overall, the genotoxicity of Pigment Red 57 is sufficiently investigated in valid genotoxicity tests for the 3 endpoints of genotoxicity: gene mutations, chromosome aberrations and aneuploidy. Pigment Red 57 did not induce gene mutations in bacteria either without metabolic activation or with Aroclor induced rat liver S9-mix or uninduced hamster liver S9- mix. Pigment Red 57 did not induce gene mutations","endpoint":"genotoxicity","ingredient":"Pigment Red 57","loael_value":"100 mg/kg bw/d","noael_unit":"mg/kg bw/d","noael_value":"100","page":26,"route":"oral","species":"rat","study_id":"sccs_o_112_noael_006"} |
openFDA substances 4 endpoints
| Source | Endpoint Type | Value | Unit | Species | Route | Duration | Study Type | Reference |
|---|---|---|---|---|---|---|---|---|
| openFDA substances | FDA UNII substance identifier | 481744AI4O | UNII | - | - | - | chemical | {"approval_status":null,"molecular_formula":"C18H12N2O6S.2Na","source_table":"substance_identifiers_fda","substance_class":"chemical","unii_code":"481744AI4O"} |
| openFDA substances | FDA UNII substance identifier | 481744AI4O | UNII | - | - | - | chemical | {"approval_status":null,"molecular_formula":"C18H12N2O6S.2Na","source_table":"substance_identifiers_fda","substance_class":"chemical","unii_code":"481744AI4O"} |
| openFDA substances | FDA UNII substance identifier | 481744AI4O | UNII | - | - | - | chemical | {"approval_status":null,"molecular_formula":"C18H12N2O6S.2Na","source_table":"substance_identifiers_fda","substance_class":"chemical","unii_code":"481744AI4O"} |
| openFDA substances | FDA UNII substance identifier | 481744AI4O | UNII | - | - | - | chemical | {"approval_status":null,"molecular_formula":"C18H12N2O6S.2Na","source_table":"substance_identifiers_fda","substance_class":"chemical","unii_code":"481744AI4O"} |