NOAEL Studies Cosmetic Ingredient

2,3-Diaminodihydropyrazolo Pyrazolone Dimethosulfonate NOAEL Studies

INCI: 2,3-DIAMINODIHYDROPYRAZOLO PYRAZOLONE DIMETHOSULFONATE

CAS: 857035-95-1

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

SCCS Opinion 16 endpoints
Source Endpoint Type Value Unit Species Route Duration Study Type Reference
SCCS Opinion NOAEL =0.03 mg/kg bw/d rat oral 90 day dermal absorption {"dose":"Safety evaluation (including calculation of the MoS) CALCULATION OF THE MARGIN OF SAFETY Oxidative conditions 2,3-diaminodihydroxypyrazolopyrazolone dimethosulfonate Absorption through the skin A = 2.94 µg/cm² Skin Area surface SAS = 580 cm2 Dermal absorption per treatment SAS x A x 0.001 = 1.71 mg Typical body weight of human = 60 kg Systemic e...","effect":"a submitted 3.3.11. Human data No data submitted 3.3.12. Special investigations No data submitted 3.3.13. Safety evaluation (including calculation of the MoS) CALCULATION OF THE MARGIN OF SAFETY Oxidative conditions 2,3-diaminodihydroxypyrazolopyrazolone dimethosulfonate Absorption through the skin A = 2.94 µg/cm² Skin Area surface SAS = 580 cm2 Dermal absorption per treatment SAS x A x 0.001 = 1.71 mg Typical body weight of human = 60 kg Systemic exposure dose (SED) SAS x A x 0.001/60 = 0.03 mg/kg bw/d No Observed Adverse Effect Level NOAEL = 300 mg/kg bw/d (90 day study, oral, rat) 50% bio-availability* = 150 mg MOS = 5000 * standard procedure according to the SCCS's Notes of Guidance for the testing of cosmetic ingredients and their safety evaluation. 3.3.14. Discussion","page":25,"pdf":"sccs_o_105.pdf","row_type":"noael_study","study_id":"sccs_o_105_noael_008"}
SCCS Opinion NOAEL =0.03 mg/kg bw/d rat oral 90 day dermal absorption {"dose":"Safety evaluation (including calculation of the MoS) CALCULATION OF THE MARGIN OF SAFETY Oxidative conditions 2,3-diaminodihydroxypyrazolopyrazolone dimethosulfonate Absorption through the skin A = 2.94 µg/cm² Skin Area surface SAS = 580 cm2 Dermal absorption per treatment SAS x A x 0.001 = 1.71 mg Typical body weight of human = 60 kg Systemic e...","effect":"a submitted 3.3.11. Human data No data submitted 3.3.12. Special investigations No data submitted 3.3.13. Safety evaluation (including calculation of the MoS) CALCULATION OF THE MARGIN OF SAFETY Oxidative conditions 2,3-diaminodihydroxypyrazolopyrazolone dimethosulfonate Absorption through the skin A = 2.94 µg/cm² Skin Area surface SAS = 580 cm2 Dermal absorption per treatment SAS x A x 0.001 = 1.71 mg Typical body weight of human = 60 kg Systemic exposure dose (SED) SAS x A x 0.001/60 = 0.03 mg/kg bw/d No Observed Adverse Effect Level NOAEL = 300 mg/kg bw/d (90 day study, oral, rat) 50% bio-availability* = 150 mg MOS = 5000 * standard procedure according to the SCCS's Notes of Guidance for the testing of cosmetic ingredients and their safety evaluation. 3.3.14. Discussion","page":25,"pdf":"sccs_o_105.pdf","row_type":"noael_study","study_id":"sccs_o_105_noael_008"}
SCCS Opinion NOAEL =0.03 mg/kg bw/d rat oral 90 day dermal absorption {"dose":"Safety evaluation (including calculation of the MoS) CALCULATION OF THE MARGIN OF SAFETY Oxidative conditions 2,3-diaminodihydroxypyrazolopyrazolone dimethosulfonate Absorption through the skin A = 2.94 µg/cm² Skin Area surface SAS = 580 cm2 Dermal absorption per treatment SAS x A x 0.001 = 1.71 mg Typical body weight of human = 60 kg Systemic e...","effect":"a submitted 3.3.11. Human data No data submitted 3.3.12. Special investigations No data submitted 3.3.13. Safety evaluation (including calculation of the MoS) CALCULATION OF THE MARGIN OF SAFETY Oxidative conditions 2,3-diaminodihydroxypyrazolopyrazolone dimethosulfonate Absorption through the skin A = 2.94 µg/cm² Skin Area surface SAS = 580 cm2 Dermal absorption per treatment SAS x A x 0.001 = 1.71 mg Typical body weight of human = 60 kg Systemic exposure dose (SED) SAS x A x 0.001/60 = 0.03 mg/kg bw/d No Observed Adverse Effect Level NOAEL = 300 mg/kg bw/d (90 day study, oral, rat) 50% bio-availability* = 150 mg MOS = 5000 * standard procedure according to the SCCS's Notes of Guidance for the testing of cosmetic ingredients and their safety evaluation. 3.3.14. Discussion","page":25,"pdf":"sccs_o_105.pdf","row_type":"noael_study","study_id":"sccs_o_105_noael_008"}
SCCS Opinion NOAEL =0.03 mg/kg bw/d rat oral 90 day dermal absorption {"dose":"Safety evaluation (including calculation of the MoS) CALCULATION OF THE MARGIN OF SAFETY Oxidative conditions 2,3-diaminodihydroxypyrazolopyrazolone dimethosulfonate Absorption through the skin A = 2.94 µg/cm² Skin Area surface SAS = 580 cm2 Dermal absorption per treatment SAS x A x 0.001 = 1.71 mg Typical body weight of human = 60 kg Systemic e...","effect":"a submitted 3.3.11. Human data No data submitted 3.3.12. Special investigations No data submitted 3.3.13. Safety evaluation (including calculation of the MoS) CALCULATION OF THE MARGIN OF SAFETY Oxidative conditions 2,3-diaminodihydroxypyrazolopyrazolone dimethosulfonate Absorption through the skin A = 2.94 µg/cm² Skin Area surface SAS = 580 cm2 Dermal absorption per treatment SAS x A x 0.001 = 1.71 mg Typical body weight of human = 60 kg Systemic exposure dose (SED) SAS x A x 0.001/60 = 0.03 mg/kg bw/d No Observed Adverse Effect Level NOAEL = 300 mg/kg bw/d (90 day study, oral, rat) 50% bio-availability* = 150 mg MOS = 5000 * standard procedure according to the SCCS's Notes of Guidance for the testing of cosmetic ingredients and their safety evaluation. 3.3.14. Discussion","page":25,"pdf":"sccs_o_105.pdf","row_type":"noael_study","study_id":"sccs_o_105_noael_008"}
SCCS Opinion NOAEL =300 mg/kg bw/day - - - NOAEL study {"citation":"Ref.: 7 Comments The results of the toxicokinetic study are not included in the study report due to the instability of the test item within the plasma matrix during the validation phase","dose":"There were no macroscopic or microscopic findings attributed to treatment with Imexine OBH at any dose-level.","effect":"marked urine discolouration. At necropsy, no relevant changes in absolute and relative organ weight were noted. There were no macroscopic or microscopic findings attributed to treatment with Imexine OBH at any dose-level. Conclusion Under the experimental conditions of this study, and based on the findings noted at urinalysis (few animals concerned, reversibility after a treatment-free period, and no correlation of these findings with any clinical pathology or histopathology changes), it was considered that the No Observed Adverse Effect Level (NOAEL) was 300 mg/kg bw/day. Ref.: 7 Comments The results of the toxicokinetic study are not included in the study report due to the instability of the test item within the plasma matrix during the validation phase of the method and the absence of a validated method. The slightly higher non dose-related blood urea concentrations in treated males when compared to controls (between 6.2 to 6.6 mmol/L vs 5.2 mmol/L, p<0.01) may be explained by an unusually low mean value of the male controls, as the female values i","page":19,"pdf":"sccs_o_105.pdf","row_type":"noael_study","study_id":"sccs_o_105_noael_001"}
SCCS Opinion NOAEL =300 mg/kg bw/d rat oral 90 day dermal absorption {"dose":"Safety evaluation (including calculation of the MoS) CALCULATION OF THE MARGIN OF SAFETY Oxidative conditions 2,3-diaminodihydroxypyrazolopyrazolone dimethosulfonate Absorption through the skin A = 2.94 µg/cm² Skin Area surface SAS = 580 cm2 Dermal absorption per treatment SAS x A x 0.001 = 1.71 mg Typical body weight of human = 60 kg Systemic e...","effect":"No data submitted 3.3.12. Special investigations No data submitted 3.3.13. Safety evaluation (including calculation of the MoS) CALCULATION OF THE MARGIN OF SAFETY Oxidative conditions 2,3-diaminodihydroxypyrazolopyrazolone dimethosulfonate Absorption through the skin A = 2.94 µg/cm² Skin Area surface SAS = 580 cm2 Dermal absorption per treatment SAS x A x 0.001 = 1.71 mg Typical body weight of human = 60 kg Systemic exposure dose (SED) SAS x A x 0.001/60 = 0.03 mg/kg bw/d No Observed Adverse Effect Level NOAEL = 300 mg/kg bw/d (90 day study, oral, rat) 50% bio-availability* = 150 mg MOS = 5000 * standard procedure according to the SCCS's Notes of Guidance for the testing of cosmetic ingredients and their safety evaluation. 3.3.14. Discussion","page":25,"pdf":"sccs_o_105.pdf","row_type":"noael_study","study_id":"sccs_o_105_noael_009"}
SCCS Opinion NOAEL =300 mg/kg bw/day - - - NOAEL study {"citation":"Ref.: 7 Comments The results of the toxicokinetic study are not included in the study report due to the instability of the test item within the plasma matrix during the validation phase","dose":"There were no macroscopic or microscopic findings attributed to treatment with Imexine OBH at any dose-level.","effect":"marked urine discolouration. At necropsy, no relevant changes in absolute and relative organ weight were noted. There were no macroscopic or microscopic findings attributed to treatment with Imexine OBH at any dose-level. Conclusion Under the experimental conditions of this study, and based on the findings noted at urinalysis (few animals concerned, reversibility after a treatment-free period, and no correlation of these findings with any clinical pathology or histopathology changes), it was considered that the No Observed Adverse Effect Level (NOAEL) was 300 mg/kg bw/day. Ref.: 7 Comments The results of the toxicokinetic study are not included in the study report due to the instability of the test item within the plasma matrix during the validation phase of the method and the absence of a validated method. The slightly higher non dose-related blood urea concentrations in treated males when compared to controls (between 6.2 to 6.6 mmol/L vs 5.2 mmol/L, p<0.01) may be explained by an unusually low mean value of the male controls, as the female values i","page":19,"pdf":"sccs_o_105.pdf","row_type":"noael_study","study_id":"sccs_o_105_noael_001"}
SCCS Opinion NOAEL =300 mg/kg bw/d rat oral 90 day dermal absorption {"dose":"Safety evaluation (including calculation of the MoS) CALCULATION OF THE MARGIN OF SAFETY Oxidative conditions 2,3-diaminodihydroxypyrazolopyrazolone dimethosulfonate Absorption through the skin A = 2.94 µg/cm² Skin Area surface SAS = 580 cm2 Dermal absorption per treatment SAS x A x 0.001 = 1.71 mg Typical body weight of human = 60 kg Systemic e...","effect":"No data submitted 3.3.12. Special investigations No data submitted 3.3.13. Safety evaluation (including calculation of the MoS) CALCULATION OF THE MARGIN OF SAFETY Oxidative conditions 2,3-diaminodihydroxypyrazolopyrazolone dimethosulfonate Absorption through the skin A = 2.94 µg/cm² Skin Area surface SAS = 580 cm2 Dermal absorption per treatment SAS x A x 0.001 = 1.71 mg Typical body weight of human = 60 kg Systemic exposure dose (SED) SAS x A x 0.001/60 = 0.03 mg/kg bw/d No Observed Adverse Effect Level NOAEL = 300 mg/kg bw/d (90 day study, oral, rat) 50% bio-availability* = 150 mg MOS = 5000 * standard procedure according to the SCCS's Notes of Guidance for the testing of cosmetic ingredients and their safety evaluation. 3.3.14. Discussion","page":25,"pdf":"sccs_o_105.pdf","row_type":"noael_study","study_id":"sccs_o_105_noael_009"}
SCCS Opinion NOAEL =300 mg/kg bw/day - - - NOAEL study {"citation":"Ref.: 7 Comments The results of the toxicokinetic study are not included in the study report due to the instability of the test item within the plasma matrix during the validation phase","dose":"There were no macroscopic or microscopic findings attributed to treatment with Imexine OBH at any dose-level.","effect":"marked urine discolouration. At necropsy, no relevant changes in absolute and relative organ weight were noted. There were no macroscopic or microscopic findings attributed to treatment with Imexine OBH at any dose-level. Conclusion Under the experimental conditions of this study, and based on the findings noted at urinalysis (few animals concerned, reversibility after a treatment-free period, and no correlation of these findings with any clinical pathology or histopathology changes), it was considered that the No Observed Adverse Effect Level (NOAEL) was 300 mg/kg bw/day. Ref.: 7 Comments The results of the toxicokinetic study are not included in the study report due to the instability of the test item within the plasma matrix during the validation phase of the method and the absence of a validated method. The slightly higher non dose-related blood urea concentrations in treated males when compared to controls (between 6.2 to 6.6 mmol/L vs 5.2 mmol/L, p<0.01) may be explained by an unusually low mean value of the male controls, as the female values i","page":19,"pdf":"sccs_o_105.pdf","row_type":"noael_study","study_id":"sccs_o_105_noael_001"}
SCCS Opinion NOAEL =300 mg/kg bw/d rat oral 90 day dermal absorption {"dose":"Safety evaluation (including calculation of the MoS) CALCULATION OF THE MARGIN OF SAFETY Oxidative conditions 2,3-diaminodihydroxypyrazolopyrazolone dimethosulfonate Absorption through the skin A = 2.94 µg/cm² Skin Area surface SAS = 580 cm2 Dermal absorption per treatment SAS x A x 0.001 = 1.71 mg Typical body weight of human = 60 kg Systemic e...","effect":"No data submitted 3.3.12. Special investigations No data submitted 3.3.13. Safety evaluation (including calculation of the MoS) CALCULATION OF THE MARGIN OF SAFETY Oxidative conditions 2,3-diaminodihydroxypyrazolopyrazolone dimethosulfonate Absorption through the skin A = 2.94 µg/cm² Skin Area surface SAS = 580 cm2 Dermal absorption per treatment SAS x A x 0.001 = 1.71 mg Typical body weight of human = 60 kg Systemic exposure dose (SED) SAS x A x 0.001/60 = 0.03 mg/kg bw/d No Observed Adverse Effect Level NOAEL = 300 mg/kg bw/d (90 day study, oral, rat) 50% bio-availability* = 150 mg MOS = 5000 * standard procedure according to the SCCS's Notes of Guidance for the testing of cosmetic ingredients and their safety evaluation. 3.3.14. Discussion","page":25,"pdf":"sccs_o_105.pdf","row_type":"noael_study","study_id":"sccs_o_105_noael_009"}
SCCS Opinion NOAEL =300 mg/kg bw/day - - - NOAEL study {"citation":"Ref.: 7 Comments The results of the toxicokinetic study are not included in the study report due to the instability of the test item within the plasma matrix during the validation phase","dose":"There were no macroscopic or microscopic findings attributed to treatment with Imexine OBH at any dose-level.","effect":"marked urine discolouration. At necropsy, no relevant changes in absolute and relative organ weight were noted. There were no macroscopic or microscopic findings attributed to treatment with Imexine OBH at any dose-level. Conclusion Under the experimental conditions of this study, and based on the findings noted at urinalysis (few animals concerned, reversibility after a treatment-free period, and no correlation of these findings with any clinical pathology or histopathology changes), it was considered that the No Observed Adverse Effect Level (NOAEL) was 300 mg/kg bw/day. Ref.: 7 Comments The results of the toxicokinetic study are not included in the study report due to the instability of the test item within the plasma matrix during the validation phase of the method and the absence of a validated method. The slightly higher non dose-related blood urea concentrations in treated males when compared to controls (between 6.2 to 6.6 mmol/L vs 5.2 mmol/L, p<0.01) may be explained by an unusually low mean value of the male controls, as the female values i","page":19,"pdf":"sccs_o_105.pdf","row_type":"noael_study","study_id":"sccs_o_105_noael_001"}
SCCS Opinion NOAEL =300 mg/kg bw/d rat oral 90 day dermal absorption {"dose":"Safety evaluation (including calculation of the MoS) CALCULATION OF THE MARGIN OF SAFETY Oxidative conditions 2,3-diaminodihydroxypyrazolopyrazolone dimethosulfonate Absorption through the skin A = 2.94 µg/cm² Skin Area surface SAS = 580 cm2 Dermal absorption per treatment SAS x A x 0.001 = 1.71 mg Typical body weight of human = 60 kg Systemic e...","effect":"No data submitted 3.3.12. Special investigations No data submitted 3.3.13. Safety evaluation (including calculation of the MoS) CALCULATION OF THE MARGIN OF SAFETY Oxidative conditions 2,3-diaminodihydroxypyrazolopyrazolone dimethosulfonate Absorption through the skin A = 2.94 µg/cm² Skin Area surface SAS = 580 cm2 Dermal absorption per treatment SAS x A x 0.001 = 1.71 mg Typical body weight of human = 60 kg Systemic exposure dose (SED) SAS x A x 0.001/60 = 0.03 mg/kg bw/d No Observed Adverse Effect Level NOAEL = 300 mg/kg bw/d (90 day study, oral, rat) 50% bio-availability* = 150 mg MOS = 5000 * standard procedure according to the SCCS's Notes of Guidance for the testing of cosmetic ingredients and their safety evaluation. 3.3.14. Discussion","page":25,"pdf":"sccs_o_105.pdf","row_type":"noael_study","study_id":"sccs_o_105_noael_009"}
SCCS Opinion NOAEL =1000 mg/kg bw/day - - developmental developmental toxicity {"citation":"Ref.: 11 Comment","dose":"Lumbar vertebrae were missing in one male foetus of the high dose group.","effect":"nt-related changes. Lumbar vertebrae were missing in one male foetus of the high dose group. There were no other effects of treatment on foetal sex ratio, foetal body weight or foetal development. Examination of the foetuses did not reveal any treatment-related external, visceral or skeletal (bone and cartilage) variation or malformations. Conclusion Under the conditions of the study, there were no embryo-foetal and teratogenic effects. Accordingly, 1000 mg/kg bw/day was identified as the No Adverse Effect Level (NOAEL) for maternal toxicity, and as the No Effect Level (NOEL) for the developmental toxicity. Ref.: 11 Comment","page":24,"pdf":"sccs_o_105.pdf","row_type":"noael_study","study_id":"sccs_o_105_noael_004"}
SCCS Opinion NOAEL =1000 mg/kg bw/day - - developmental developmental toxicity {"citation":"Ref.: 11 Comment","dose":"Lumbar vertebrae were missing in one male foetus of the high dose group.","effect":"nt-related changes. Lumbar vertebrae were missing in one male foetus of the high dose group. There were no other effects of treatment on foetal sex ratio, foetal body weight or foetal development. Examination of the foetuses did not reveal any treatment-related external, visceral or skeletal (bone and cartilage) variation or malformations. Conclusion Under the conditions of the study, there were no embryo-foetal and teratogenic effects. Accordingly, 1000 mg/kg bw/day was identified as the No Adverse Effect Level (NOAEL) for maternal toxicity, and as the No Effect Level (NOEL) for the developmental toxicity. Ref.: 11 Comment","page":24,"pdf":"sccs_o_105.pdf","row_type":"noael_study","study_id":"sccs_o_105_noael_004"}
SCCS Opinion NOAEL =1000 mg/kg bw/day - - developmental developmental toxicity {"citation":"Ref.: 11 Comment","dose":"Lumbar vertebrae were missing in one male foetus of the high dose group.","effect":"nt-related changes. Lumbar vertebrae were missing in one male foetus of the high dose group. There were no other effects of treatment on foetal sex ratio, foetal body weight or foetal development. Examination of the foetuses did not reveal any treatment-related external, visceral or skeletal (bone and cartilage) variation or malformations. Conclusion Under the conditions of the study, there were no embryo-foetal and teratogenic effects. Accordingly, 1000 mg/kg bw/day was identified as the No Adverse Effect Level (NOAEL) for maternal toxicity, and as the No Effect Level (NOEL) for the developmental toxicity. Ref.: 11 Comment","page":24,"pdf":"sccs_o_105.pdf","row_type":"noael_study","study_id":"sccs_o_105_noael_004"}
SCCS Opinion NOAEL =1000 mg/kg bw/day - - developmental developmental toxicity {"citation":"Ref.: 11 Comment","dose":"Lumbar vertebrae were missing in one male foetus of the high dose group.","effect":"nt-related changes. Lumbar vertebrae were missing in one male foetus of the high dose group. There were no other effects of treatment on foetal sex ratio, foetal body weight or foetal development. Examination of the foetuses did not reveal any treatment-related external, visceral or skeletal (bone and cartilage) variation or malformations. Conclusion Under the conditions of the study, there were no embryo-foetal and teratogenic effects. Accordingly, 1000 mg/kg bw/day was identified as the No Adverse Effect Level (NOAEL) for maternal toxicity, and as the No Effect Level (NOEL) for the developmental toxicity. Ref.: 11 Comment","page":24,"pdf":"sccs_o_105.pdf","row_type":"noael_study","study_id":"sccs_o_105_noael_004"}
ECHA 3 endpoints
Source Endpoint Type Value Unit Species Route Duration Study Type Reference
ECHA LEL =1000 mg/kg bw/day Rat oral - reproduction developmental QUALITY=1 (reliable without restriction); STORED_SOURCE_RECORD=https://clowder.edap-cluster.com/files/66a7d23de4b0a7c65d232241; RECORD_SOURCE_LEVEL=Extraction document; SOURCE_URL=https://echa.europa.eu/; SUBSOURCE_URL=https://echa.europa.eu/registration-dossier/-/registered-dossier/3841/7/9/3?documentUUID=ea9c35a5-a10d-4983-8c96-0cde50824c78; YEAR=2006; ORIGINAL_YEAR=2006; STUDY_GROUP=ECHA IUCLID:15822034: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_18458c75eba60860cd6f74983086f354
ECHA NOAEL =300 mg/kg bw/day Rat oral subchronic; 13 weeks subchronic QUALITY=1 (reliable without restriction); STORED_SOURCE_RECORD=https://clowder.edap-cluster.com/files/669eaf31e4b0a7c65d1ccf01; RECORD_SOURCE_LEVEL=Extraction document; SOURCE_URL=https://echa.europa.eu/; SUBSOURCE_URL=https://echa.europa.eu/registration-dossier/-/registered-dossier/3841/7/6/2?documentUUID=ea9c35a5-a10d-4983-8c96-0cde50824c78; YEAR=2006; ORIGINAL_YEAR=2006; STUDY_GROUP=ECHA IUCLID:15837409:M/F:--; 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_4dd97b06daf2f3213b789374ae07d362
ECHA NOAEL =1000 mg/kg bw/day Rat oral short-term; 15 days short-term QUALITY=1 (reliable without restriction); STORED_SOURCE_RECORD=https://clowder.edap-cluster.com/files/66a7cbffe4b0a7c65d2287d5; RECORD_SOURCE_LEVEL=Extraction document; SOURCE_URL=https://echa.europa.eu/; SUBSOURCE_URL=https://echa.europa.eu/registration-dossier/-/registered-dossier/3841/7/6/2?documentUUID=ea9c35a5-a10d-4983-8c96-0cde50824c78; YEAR=2006; ORIGINAL_YEAR=2006; STUDY_GROUP=ECHA IUCLID:15844132:M/F:--; 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_36a25dc2a19bb8000b60d7e4dd316c59
Regulatory source 12 endpoints
Source Endpoint Type Value Unit Species Route Duration Study Type Reference
Regulatory source - 300 mg/kg bw/day - - - - SOURCE_SUBDIR=sccs_o_105; REPORT_TITLE=OPINION ON 2,3-Diaminodihydroxypyrazolopyrazolone dimethosulfonate COLIPA n° A159; OPINION_NUMBER=SCCS/1470/12; COMMITTEE=Scientific Committee on Consumer Safety (SCCS); REPORT_DATE=18 September 2012; VALUE_TEXT=300; DOSE=There were no macroscopic or microscopic findings attributed to treatment with Imexine OBH at any dose-level.; EFFECT=marked urine discolouration. At necropsy, no relevant changes in absolute and relative organ weight were noted. There were no macroscopic or microscopic findings attributed to treatment with Imexine OBH at any dose-level. Conclusion Under the experimental conditions of this study, and based on the findings noted at urinalysis (few animals concerned, reversibility after a treatment-free period, and no correlation of these findings with any clinical pathology or histopathology changes), it was considered that the No Observed Adverse Effect Level (NOAEL) was 300 mg/kg bw/day. Ref.: 7 Comments The results of the toxicokinetic study are not included in the study report due to the instability of the test item within the plasma matrix during the validation phase of the method and the absence of a validated method. The slightly higher non dose-related blood urea concentrations in treated males when compared to controls (between 6.2 to 6.6 mmol/L vs 5.2 mmol/L, p<0.01) may be explained by an unusually low mean value of the male controls, as the female values i; CITATION=Ref.: 7 Comments The results of the toxicokinetic study are not included in the study report due to the instability of the test item within the plasma matrix during the validation phase; CITATION_NUMBERS=[7]; REFERENCE=Ref.: 7 Comments The results of the toxicokinetic study are not included in the study report due to the instability of the test item within the plasma matrix during the validation phase; DETAILS_JSON={"cas_number":"857035-95-1","citation":"Ref.: 7 Comments The results of the toxicokinetic study are not included in the study report due to the instability of the test item within the plasma matrix during the validation phase","dose":"There were no macroscopic or microscopic findings attributed to treatment with Imexine OBH at any dose-level.","duration":"","effect":"marked urine discolouration. At necropsy, no relevant changes in absolute and relative organ weight were noted. There were no macroscopic or microscopic findings attributed to treatment with Imexine OBH at any dose-level. Conclusion Under the experimental conditions of this study, and based on the findings noted at urinalysis (few animals concerned, reversibility after a treatment-free period, and no correlation of these findings with any clinical pathology or histopathology changes), it was considered that the No Observed Adverse Effect Level (NOAEL) was 300 mg/kg bw/day. Ref.: 7 Comments The results of the toxicokinetic study are not included in the study report due to the instability of the test item within the plasma matrix during the validation phase of the method and the absence of a validated method. The slightly higher non dose-related blood urea concentrations in treated males when compared to controls (between 6.2 to 6.6 mmol/L vs 5.2 mmol/L, p<0.01) may be explained by an unusually low mean value of the male controls, as the female values i","endpoint":"","ingredient":"2,3-Diaminodihydropyrazolopyrazolone dimethosulfonate (INCI-name)","loael_value":"","noael_unit":"mg/kg bw/day","noael_value":"300","page":19,"route":"","species":"","study_id":"sccs_o_105_noael_001"}
Regulatory source - 300 mg/kg bw/day - - - - SOURCE_SUBDIR=sccs_o_105; REPORT_TITLE=OPINION ON 2,3-Diaminodihydroxypyrazolopyrazolone dimethosulfonate COLIPA n° A159; OPINION_NUMBER=SCCS/1470/12; COMMITTEE=Scientific Committee on Consumer Safety (SCCS); REPORT_DATE=18 September 2012; VALUE_TEXT=300; DOSE=There were no macroscopic or microscopic findings attributed to treatment with Imexine OBH at any dose-level.; EFFECT=necropsy, no relevant changes in absolute and relative organ weight were noted. There were no macroscopic or microscopic findings attributed to treatment with Imexine OBH at any dose-level. Conclusion Under the experimental conditions of this study, and based on the findings noted at urinalysis (few animals concerned, reversibility after a treatment-free period, and no correlation of these findings with any clinical pathology or histopathology changes), it was considered that the No Observed Adverse Effect Level (NOAEL) was 300 mg/kg bw/day. Ref.: 7 Comments The results of the toxicokinetic study are not included in the study report due to the instability of the test item within the plasma matrix during the validation phase of the method and the absence of a validated method. The slightly higher non dose-related blood urea concentrations in treated males when compared to controls (between 6.2 to 6.6 mmol/L vs 5.2 mmol/L, p<0.01) may be explained by an unusually low mean value of the male controls, as the female values includin; CITATION=Ref.: 7 Comments The results of the toxicokinetic study are not included in the study report due to the instability of the test item within the plasma matrix during the validation phase; CITATION_NUMBERS=[7]; REFERENCE=Ref.: 7 Comments The results of the toxicokinetic study are not included in the study report due to the instability of the test item within the plasma matrix during the validation phase; DETAILS_JSON={"cas_number":"857035-95-1","citation":"Ref.: 7 Comments The results of the toxicokinetic study are not included in the study report due to the instability of the test item within the plasma matrix during the validation phase","dose":"There were no macroscopic or microscopic findings attributed to treatment with Imexine OBH at any dose-level.","duration":"","effect":"necropsy, no relevant changes in absolute and relative organ weight were noted. There were no macroscopic or microscopic findings attributed to treatment with Imexine OBH at any dose-level. Conclusion Under the experimental conditions of this study, and based on the findings noted at urinalysis (few animals concerned, reversibility after a treatment-free period, and no correlation of these findings with any clinical pathology or histopathology changes), it was considered that the No Observed Adverse Effect Level (NOAEL) was 300 mg/kg bw/day. Ref.: 7 Comments The results of the toxicokinetic study are not included in the study report due to the instability of the test item within the plasma matrix during the validation phase of the method and the absence of a validated method. The slightly higher non dose-related blood urea concentrations in treated males when compared to controls (between 6.2 to 6.6 mmol/L vs 5.2 mmol/L, p<0.01) may be explained by an unusually low mean value of the male controls, as the female values includin","endpoint":"","ingredient":"2,3-Diaminodihydropyrazolopyrazolone dimethosulfonate (INCI-name)","loael_value":"","noael_unit":"mg/kg bw/day","noael_value":"300","page":19,"route":"","species":"","study_id":"sccs_o_105_noael_002"}
Regulatory source - 300 mg/kg bw/day - - - - SOURCE_SUBDIR=sccs_o_105; REPORT_TITLE=OPINION ON 2,3-Diaminodihydroxypyrazolopyrazolone dimethosulfonate COLIPA n° A159; OPINION_NUMBER=SCCS/1470/12; COMMITTEE=Scientific Committee on Consumer Safety (SCCS); REPORT_DATE=18 September 2012; VALUE_TEXT=300; DOSE=ary parameters discussed above revealed dose-related increases for the bilirubin concentrations in females and dose-related increases for the glucose and nitrite concentrations in males and females above 100 mg/kg bw/day.; EFFECT=ary parameters discussed above revealed dose-related increases for the bilirubin concentrations in females and dose-related increases for the glucose and nitrite concentrations in males and females above 100 mg/kg bw/day. No hyperbilirubinaemia or hyperglycaemia was found. It is agreed that the nitrite determinations might be influenced by the highly coloured urine samples at mid and high dose and thus appear questionable. The positive (reversible) bilirubin and glucose findings are not considered adverse. Thus, a NOAEL of 300 mg/kg bw/day is derived.; CITATION_NUMBERS=[]; DETAILS_JSON={"cas_number":"857035-95-1","citation":"","dose":"ary parameters discussed above revealed dose-related increases for the bilirubin concentrations in females and dose-related increases for the glucose and nitrite concentrations in males and females above 100 mg/kg bw/day.","duration":"","effect":"ary parameters discussed above revealed dose-related increases for the bilirubin concentrations in females and dose-related increases for the glucose and nitrite concentrations in males and females above 100 mg/kg bw/day. No hyperbilirubinaemia or hyperglycaemia was found. It is agreed that the nitrite determinations might be influenced by the highly coloured urine samples at mid and high dose and thus appear questionable. The positive (reversible) bilirubin and glucose findings are not considered adverse. Thus, a NOAEL of 300 mg/kg bw/day is derived.","endpoint":"","ingredient":"2,3-Diaminodihydropyrazolopyrazolone dimethosulfonate (INCI-name)","loael_value":"","noael_unit":"mg/kg bw/day","noael_value":"300","page":19,"route":"","species":"","study_id":"sccs_o_105_noael_003"}
Regulatory source - 300 mg/kg bw/day rat oral - - SOURCE_SUBDIR=sccs_o_105; REPORT_TITLE=OPINION ON 2,3-Diaminodihydroxypyrazolopyrazolone dimethosulfonate COLIPA n° A159; OPINION_NUMBER=SCCS/1470/12; COMMITTEE=Scientific Committee on Consumer Safety (SCCS); REPORT_DATE=18 September 2012; VALUE_TEXT=300; DOSE=dose group died or were found moribund (weeks 10 and 13).; EFFECT=dose group died or were found moribund (weeks 10 and 13). The deaths were considered test item treatment-related. Main clinical signs, excessive salivation in all animals from week one until the end of the dosing period and loud or abdominal breathing in some animals were only observed in the high dose group. The urinalysis revealed dose-related enhanced bilirubin and glucose concentrations in the mid and high dose group (not accompanied by bilirubinaemia or glycemia). These effects are not considered adverse. The NOAEL of this study is considered 300 mg/kg bw/day. The potential effects of 2,3-Diaminodihydropyrazolopyrazolone dimethosulfonate on embryo-foetal development were evaluated in an oral (gavage) study where pregnant rats were given 2,3-Diaminodihydropyrazolopyrazolone dimethosulfonate at 100, 300 or 1000 mg/kg bw/day during the sensitive period of organogenesis. At 1000 mg/kg bw/day, a female showed loud and abdominal breathing and another excessive salivation. There were no signs of toxicity on embryo-foetal developme; CITATION_NUMBERS=[]; DETAILS_JSON={"cas_number":"857035-95-1","citation":"","dose":"dose group died or were found moribund (weeks 10 and 13).","duration":"","effect":"dose group died or were found moribund (weeks 10 and 13). The deaths were considered test item treatment-related. Main clinical signs, excessive salivation in all animals from week one until the end of the dosing period and loud or abdominal breathing in some animals were only observed in the high dose group. The urinalysis revealed dose-related enhanced bilirubin and glucose concentrations in the mid and high dose group (not accompanied by bilirubinaemia or glycemia). These effects are not considered adverse. The NOAEL of this study is considered 300 mg/kg bw/day. The potential effects of 2,3-Diaminodihydropyrazolopyrazolone dimethosulfonate on embryo-foetal development were evaluated in an oral (gavage) study where pregnant rats were given 2,3-Diaminodihydropyrazolopyrazolone dimethosulfonate at 100, 300 or 1000 mg/kg bw/day during the sensitive period of organogenesis. At 1000 mg/kg bw/day, a female showed loud and abdominal breathing and another excessive salivation. There were no signs of toxicity on embryo-foetal developme","endpoint":"","ingredient":"2,3-Diaminodihydropyrazolopyrazolone dimethosulfonate (INCI-name)","loael_value":"","noael_unit":"mg/kg bw/day","noael_value":"300","page":26,"route":"oral","species":"rat","study_id":"sccs_o_105_noael_010"}
Regulatory source dermal absorption =0.03 mg/kg bw/d rat oral 90 day dermal absorption SOURCE_SUBDIR=sccs_o_105; REPORT_TITLE=OPINION ON 2,3-Diaminodihydroxypyrazolopyrazolone dimethosulfonate COLIPA n° A159; OPINION_NUMBER=SCCS/1470/12; COMMITTEE=Scientific Committee on Consumer Safety (SCCS); REPORT_DATE=18 September 2012; VALUE_TEXT== 0.03; DOSE=Safety evaluation (including calculation of the MoS) CALCULATION OF THE MARGIN OF SAFETY Oxidative conditions 2,3-diaminodihydroxypyrazolopyrazolone dimethosulfonate Absorption through the skin A = 2.94 µg/cm² Skin Area surface SAS = 580 cm2 Dermal absorption per treatment SAS x A x 0.001 = 1.71 mg Typical body weight of human = 60 kg Systemic e...; EFFECT=a submitted 3.3.11. Human data No data submitted 3.3.12. Special investigations No data submitted 3.3.13. Safety evaluation (including calculation of the MoS) CALCULATION OF THE MARGIN OF SAFETY Oxidative conditions 2,3-diaminodihydroxypyrazolopyrazolone dimethosulfonate Absorption through the skin A = 2.94 µg/cm² Skin Area surface SAS = 580 cm2 Dermal absorption per treatment SAS x A x 0.001 = 1.71 mg Typical body weight of human = 60 kg Systemic exposure dose (SED) SAS x A x 0.001/60 = 0.03 mg/kg bw/d No Observed Adverse Effect Level NOAEL = 300 mg/kg bw/d (90 day study, oral, rat) 50% bio-availability* = 150 mg MOS = 5000 * standard procedure according to the SCCS's Notes of Guidance for the testing of cosmetic ingredients and their safety evaluation. 3.3.14. Discussion; CITATION_NUMBERS=[]; DETAILS_JSON={"cas_number":"857035-95-1","citation":"","dose":"Safety evaluation (including calculation of the MoS) CALCULATION OF THE MARGIN OF SAFETY Oxidative conditions 2,3-diaminodihydroxypyrazolopyrazolone dimethosulfonate Absorption through the skin A = 2.94 µg/cm² Skin Area surface SAS = 580 cm2 Dermal absorption per treatment SAS x A x 0.001 = 1.71 mg Typical body weight of human = 60 kg Systemic e...","duration":"90 day","effect":"a submitted 3.3.11. Human data No data submitted 3.3.12. Special investigations No data submitted 3.3.13. Safety evaluation (including calculation of the MoS) CALCULATION OF THE MARGIN OF SAFETY Oxidative conditions 2,3-diaminodihydroxypyrazolopyrazolone dimethosulfonate Absorption through the skin A = 2.94 µg/cm² Skin Area surface SAS = 580 cm2 Dermal absorption per treatment SAS x A x 0.001 = 1.71 mg Typical body weight of human = 60 kg Systemic exposure dose (SED) SAS x A x 0.001/60 = 0.03 mg/kg bw/d No Observed Adverse Effect Level NOAEL = 300 mg/kg bw/d (90 day study, oral, rat) 50% bio-availability* = 150 mg MOS = 5000 * standard procedure according to the SCCS's Notes of Guidance for the testing of cosmetic ingredients and their safety evaluation. 3.3.14. Discussion","endpoint":"dermal absorption","ingredient":"2,3-Diaminodihydropyrazolopyrazolone dimethosulfonate (INCI-name)","loael_value":"","noael_unit":"mg/kg bw/d","noael_value":"= 0.03","page":25,"route":"oral","species":"rat","study_id":"sccs_o_105_noael_008"}
Regulatory source dermal absorption =300 mg/kg bw/d rat oral 90 day dermal absorption SOURCE_SUBDIR=sccs_o_105; REPORT_TITLE=OPINION ON 2,3-Diaminodihydroxypyrazolopyrazolone dimethosulfonate COLIPA n° A159; OPINION_NUMBER=SCCS/1470/12; COMMITTEE=Scientific Committee on Consumer Safety (SCCS); REPORT_DATE=18 September 2012; VALUE_TEXT== 300; DOSE=Safety evaluation (including calculation of the MoS) CALCULATION OF THE MARGIN OF SAFETY Oxidative conditions 2,3-diaminodihydroxypyrazolopyrazolone dimethosulfonate Absorption through the skin A = 2.94 µg/cm² Skin Area surface SAS = 580 cm2 Dermal absorption per treatment SAS x A x 0.001 = 1.71 mg Typical body weight of human = 60 kg Systemic e...; EFFECT=No data submitted 3.3.12. Special investigations No data submitted 3.3.13. Safety evaluation (including calculation of the MoS) CALCULATION OF THE MARGIN OF SAFETY Oxidative conditions 2,3-diaminodihydroxypyrazolopyrazolone dimethosulfonate Absorption through the skin A = 2.94 µg/cm² Skin Area surface SAS = 580 cm2 Dermal absorption per treatment SAS x A x 0.001 = 1.71 mg Typical body weight of human = 60 kg Systemic exposure dose (SED) SAS x A x 0.001/60 = 0.03 mg/kg bw/d No Observed Adverse Effect Level NOAEL = 300 mg/kg bw/d (90 day study, oral, rat) 50% bio-availability* = 150 mg MOS = 5000 * standard procedure according to the SCCS's Notes of Guidance for the testing of cosmetic ingredients and their safety evaluation. 3.3.14. Discussion; CITATION_NUMBERS=[]; DETAILS_JSON={"cas_number":"857035-95-1","citation":"","dose":"Safety evaluation (including calculation of the MoS) CALCULATION OF THE MARGIN OF SAFETY Oxidative conditions 2,3-diaminodihydroxypyrazolopyrazolone dimethosulfonate Absorption through the skin A = 2.94 µg/cm² Skin Area surface SAS = 580 cm2 Dermal absorption per treatment SAS x A x 0.001 = 1.71 mg Typical body weight of human = 60 kg Systemic e...","duration":"90 day","effect":"No data submitted 3.3.12. Special investigations No data submitted 3.3.13. Safety evaluation (including calculation of the MoS) CALCULATION OF THE MARGIN OF SAFETY Oxidative conditions 2,3-diaminodihydroxypyrazolopyrazolone dimethosulfonate Absorption through the skin A = 2.94 µg/cm² Skin Area surface SAS = 580 cm2 Dermal absorption per treatment SAS x A x 0.001 = 1.71 mg Typical body weight of human = 60 kg Systemic exposure dose (SED) SAS x A x 0.001/60 = 0.03 mg/kg bw/d No Observed Adverse Effect Level NOAEL = 300 mg/kg bw/d (90 day study, oral, rat) 50% bio-availability* = 150 mg MOS = 5000 * standard procedure according to the SCCS's Notes of Guidance for the testing of cosmetic ingredients and their safety evaluation. 3.3.14. Discussion","endpoint":"dermal absorption","ingredient":"2,3-Diaminodihydropyrazolopyrazolone dimethosulfonate (INCI-name)","loael_value":"","noael_unit":"mg/kg bw/d","noael_value":"= 300","page":25,"route":"oral","species":"rat","study_id":"sccs_o_105_noael_009"}
Regulatory source developmental toxicity 300 mg/kg bw/day rabbit - 90-day developmental toxicity SOURCE_SUBDIR=sccs_o_105; REPORT_TITLE=OPINION ON 2,3-Diaminodihydroxypyrazolopyrazolone dimethosulfonate COLIPA n° A159; OPINION_NUMBER=SCCS/1470/12; COMMITTEE=Scientific Committee on Consumer Safety (SCCS); REPORT_DATE=18 September 2012; VALUE_TEXT=300; DOSE=Lumbar vertebrae absent in one foetus of the high dose group were considered a malformation by the study authors but not treatment-related.; EFFECT=the growth in utero. Lumbar vertebrae absent in one foetus of the high dose group were considered a malformation by the study authors but not treatment-related. 2,3- Diaminodihydropyrazolopyrazolone dimethosulfonate is regarded to have no embryotoxic or teratogenic potential under the conditions of the study. Based on the clinical symptoms of two females in the high dose group, which were similar to the clinical symptoms at the same dose in the 90-day toxicity study, a dose of 300 mg/kg bw/day is considered as the NOAEL for maternal toxicity. The NOAEL for the developmental toxicity is considered 1000 mg/kg bw/day. Irritation, sensitisation Under the experimental conditions, the test item was non-irritant when applied topically to rabbit skin. It was severely irritant when applied neat to rabbit eye. A 5% dilution was slightly irritant to the rabbit eyes. Under the experimental conditions, the test item did not induce contact sensitization in the murine Local Lymph Node Assay. No firm conclusion regarding the sensitising poten; CITATION_NUMBERS=[]; DETAILS_JSON={"cas_number":"857035-95-1","citation":"","dose":"Lumbar vertebrae absent in one foetus of the high dose group were considered a malformation by the study authors but not treatment-related.","duration":"90-day","effect":"the growth in utero. Lumbar vertebrae absent in one foetus of the high dose group were considered a malformation by the study authors but not treatment-related. 2,3- Diaminodihydropyrazolopyrazolone dimethosulfonate is regarded to have no embryotoxic or teratogenic potential under the conditions of the study. Based on the clinical symptoms of two females in the high dose group, which were similar to the clinical symptoms at the same dose in the 90-day toxicity study, a dose of 300 mg/kg bw/day is considered as the NOAEL for maternal toxicity. The NOAEL for the developmental toxicity is considered 1000 mg/kg bw/day. Irritation, sensitisation Under the experimental conditions, the test item was non-irritant when applied topically to rabbit skin. It was severely irritant when applied neat to rabbit eye. A 5% dilution was slightly irritant to the rabbit eyes. Under the experimental conditions, the test item did not induce contact sensitization in the murine Local Lymph Node Assay. No firm conclusion regarding the sensitising poten","endpoint":"developmental toxicity","ingredient":"2,3-Diaminodihydropyrazolopyrazolone dimethosulfonate (INCI-name)","loael_value":"","noael_unit":"mg/kg bw/day","noael_value":"300","page":26,"route":"","species":"rabbit","study_id":"sccs_o_105_noael_011"}
Regulatory source developmental toxicity 1000 mg/kg bw/day - - developmental developmental toxicity SOURCE_SUBDIR=sccs_o_105; REPORT_TITLE=OPINION ON 2,3-Diaminodihydroxypyrazolopyrazolone dimethosulfonate COLIPA n° A159; OPINION_NUMBER=SCCS/1470/12; COMMITTEE=Scientific Committee on Consumer Safety (SCCS); REPORT_DATE=18 September 2012; VALUE_TEXT=1000; DOSE=Lumbar vertebrae were missing in one male foetus of the high dose group.; EFFECT=nt-related changes. Lumbar vertebrae were missing in one male foetus of the high dose group. There were no other effects of treatment on foetal sex ratio, foetal body weight or foetal development. Examination of the foetuses did not reveal any treatment-related external, visceral or skeletal (bone and cartilage) variation or malformations. Conclusion Under the conditions of the study, there were no embryo-foetal and teratogenic effects. Accordingly, 1000 mg/kg bw/day was identified as the No Adverse Effect Level (NOAEL) for maternal toxicity, and as the No Effect Level (NOEL) for the developmental toxicity. Ref.: 11 Comment; CITATION=Ref.: 11 Comment; CITATION_NUMBERS=[11]; REFERENCE=Ref.: 11 Comment; DETAILS_JSON={"cas_number":"857035-95-1","citation":"Ref.: 11 Comment","dose":"Lumbar vertebrae were missing in one male foetus of the high dose group.","duration":"developmental","effect":"nt-related changes. Lumbar vertebrae were missing in one male foetus of the high dose group. There were no other effects of treatment on foetal sex ratio, foetal body weight or foetal development. Examination of the foetuses did not reveal any treatment-related external, visceral or skeletal (bone and cartilage) variation or malformations. Conclusion Under the conditions of the study, there were no embryo-foetal and teratogenic effects. Accordingly, 1000 mg/kg bw/day was identified as the No Adverse Effect Level (NOAEL) for maternal toxicity, and as the No Effect Level (NOEL) for the developmental toxicity. Ref.: 11 Comment","endpoint":"developmental toxicity","ingredient":"2,3-Diaminodihydropyrazolopyrazolone dimethosulfonate (INCI-name)","loael_value":"","noael_unit":"mg/kg bw/day","noael_value":"1000","page":24,"route":"","species":"","study_id":"sccs_o_105_noael_004"}
Regulatory source developmental toxicity 1000 mg/kg bw/day - - developmental developmental toxicity SOURCE_SUBDIR=sccs_o_105; REPORT_TITLE=OPINION ON 2,3-Diaminodihydroxypyrazolopyrazolone dimethosulfonate COLIPA n° A159; OPINION_NUMBER=SCCS/1470/12; COMMITTEE=Scientific Committee on Consumer Safety (SCCS); REPORT_DATE=18 September 2012; VALUE_TEXT=1000; DOSE=ale foetus of the high dose group.; EFFECT=ale foetus of the high dose group. There were no other effects of treatment on foetal sex ratio, foetal body weight or foetal development. Examination of the foetuses did not reveal any treatment-related external, visceral or skeletal (bone and cartilage) variation or malformations. Conclusion Under the conditions of the study, there were no embryo-foetal and teratogenic effects. Accordingly, 1000 mg/kg bw/day was identified as the No Adverse Effect Level (NOAEL) for maternal toxicity, and as the No Effect Level (NOEL) for the developmental toxicity. Ref.: 11 Comment; CITATION=Ref.: 11 Comment; CITATION_NUMBERS=[11]; REFERENCE=Ref.: 11 Comment; DETAILS_JSON={"cas_number":"857035-95-1","citation":"Ref.: 11 Comment","dose":"ale foetus of the high dose group.","duration":"developmental","effect":"ale foetus of the high dose group. There were no other effects of treatment on foetal sex ratio, foetal body weight or foetal development. Examination of the foetuses did not reveal any treatment-related external, visceral or skeletal (bone and cartilage) variation or malformations. Conclusion Under the conditions of the study, there were no embryo-foetal and teratogenic effects. Accordingly, 1000 mg/kg bw/day was identified as the No Adverse Effect Level (NOAEL) for maternal toxicity, and as the No Effect Level (NOEL) for the developmental toxicity. Ref.: 11 Comment","endpoint":"developmental toxicity","ingredient":"2,3-Diaminodihydropyrazolopyrazolone dimethosulfonate (INCI-name)","loael_value":"","noael_unit":"mg/kg bw/day","noael_value":"1000","page":24,"route":"","species":"","study_id":"sccs_o_105_noael_005"}
Regulatory source developmental toxicity 1000 mg/kg bw/day rabbit - 90-day developmental toxicity SOURCE_SUBDIR=sccs_o_105; REPORT_TITLE=OPINION ON 2,3-Diaminodihydroxypyrazolopyrazolone dimethosulfonate COLIPA n° A159; OPINION_NUMBER=SCCS/1470/12; COMMITTEE=Scientific Committee on Consumer Safety (SCCS); REPORT_DATE=18 September 2012; VALUE_TEXT=1000; DOSE=brae absent in one foetus of the high dose group were considered a malformation by the study authors but not treatment-related.; EFFECT=brae absent in one foetus of the high dose group were considered a malformation by the study authors but not treatment-related. 2,3- Diaminodihydropyrazolopyrazolone dimethosulfonate is regarded to have no embryotoxic or teratogenic potential under the conditions of the study. Based on the clinical symptoms of two females in the high dose group, which were similar to the clinical symptoms at the same dose in the 90-day toxicity study, a dose of 300 mg/kg bw/day is considered as the NOAEL for maternal toxicity. The NOAEL for the developmental toxicity is considered 1000 mg/kg bw/day. Irritation, sensitisation Under the experimental conditions, the test item was non-irritant when applied topically to rabbit skin. It was severely irritant when applied neat to rabbit eye. A 5% dilution was slightly irritant to the rabbit eyes. Under the experimental conditions, the test item did not induce contact sensitization in the murine Local Lymph Node Assay. No firm conclusion regarding the sensitising potential of 2,3-diaminodihydropyrazol; CITATION_NUMBERS=[]; DETAILS_JSON={"cas_number":"857035-95-1","citation":"","dose":"brae absent in one foetus of the high dose group were considered a malformation by the study authors but not treatment-related.","duration":"90-day","effect":"brae absent in one foetus of the high dose group were considered a malformation by the study authors but not treatment-related. 2,3- Diaminodihydropyrazolopyrazolone dimethosulfonate is regarded to have no embryotoxic or teratogenic potential under the conditions of the study. Based on the clinical symptoms of two females in the high dose group, which were similar to the clinical symptoms at the same dose in the 90-day toxicity study, a dose of 300 mg/kg bw/day is considered as the NOAEL for maternal toxicity. The NOAEL for the developmental toxicity is considered 1000 mg/kg bw/day. Irritation, sensitisation Under the experimental conditions, the test item was non-irritant when applied topically to rabbit skin. It was severely irritant when applied neat to rabbit eye. A 5% dilution was slightly irritant to the rabbit eyes. Under the experimental conditions, the test item did not induce contact sensitization in the murine Local Lymph Node Assay. No firm conclusion regarding the sensitising potential of 2,3-diaminodihydropyrazol","endpoint":"developmental toxicity","ingredient":"2,3-Diaminodihydropyrazolopyrazolone dimethosulfonate (INCI-name)","loael_value":"","noael_unit":"mg/kg bw/day","noael_value":"1000","page":26,"route":"","species":"rabbit","study_id":"sccs_o_105_noael_012"}
Regulatory source repeated dose toxicity 300 mg/kg bw/day - - 90-day repeated dose toxicity SOURCE_SUBDIR=sccs_o_105; REPORT_TITLE=OPINION ON 2,3-Diaminodihydroxypyrazolopyrazolone dimethosulfonate COLIPA n° A159; OPINION_NUMBER=SCCS/1470/12; COMMITTEE=Scientific Committee on Consumer Safety (SCCS); REPORT_DATE=18 September 2012; VALUE_TEXT=300; DOSE=SCCS/1470/12 Opinion on 2,3-diaminodihydroxypyrazolopyrazolone dimethosulfonate ___________________________________________________________________________________________ 25 The clinical symptoms reported for two females in the high dose group are considered adverse, as there were similar clinical symptoms observed in the high dose group at the...; EFFECT=SCCS/1470/12 Opinion on 2,3-diaminodihydroxypyrazolopyrazolone dimethosulfonate ___________________________________________________________________________________________ 25 The clinical symptoms reported for two females in the high dose group are considered adverse, as there were similar clinical symptoms observed in the high dose group at the same dose in the 90-day repeated dose toxicity study [7]. Therefore, the NOAEL for maternal toxicity is considered 300 mg/kg bw/day. Lumbar vertebrae absent in one foetus of the high dose group were considered an incidental malformation by the study authors but not treatment-related. The NOAEL for the developmental toxicity is considered 1000 mg/kg bw/day. 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 subm; CITATION_NUMBERS=[]; DETAILS_JSON={"cas_number":"857035-95-1","citation":"","dose":"SCCS/1470/12 Opinion on 2,3-diaminodihydroxypyrazolopyrazolone dimethosulfonate ___________________________________________________________________________________________ 25 The clinical symptoms reported for two females in the high dose group are considered adverse, as there were similar clinical symptoms observed in the high dose group at the...","duration":"90-day","effect":"SCCS/1470/12 Opinion on 2,3-diaminodihydroxypyrazolopyrazolone dimethosulfonate ___________________________________________________________________________________________ 25 The clinical symptoms reported for two females in the high dose group are considered adverse, as there were similar clinical symptoms observed in the high dose group at the same dose in the 90-day repeated dose toxicity study [7]. Therefore, the NOAEL for maternal toxicity is considered 300 mg/kg bw/day. Lumbar vertebrae absent in one foetus of the high dose group were considered an incidental malformation by the study authors but not treatment-related. The NOAEL for the developmental toxicity is considered 1000 mg/kg bw/day. 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 subm","endpoint":"repeated dose toxicity","ingredient":"2,3-Diaminodihydropyrazolopyrazolone dimethosulfonate (INCI-name)","loael_value":"","noael_unit":"mg/kg bw/day","noael_value":"300","page":25,"route":"","species":"","study_id":"sccs_o_105_noael_006"}
Regulatory source repeated dose toxicity 1000 mg/kg bw/day human - 90-day repeated dose toxicity SOURCE_SUBDIR=sccs_o_105; REPORT_TITLE=OPINION ON 2,3-Diaminodihydroxypyrazolopyrazolone dimethosulfonate COLIPA n° A159; OPINION_NUMBER=SCCS/1470/12; COMMITTEE=Scientific Committee on Consumer Safety (SCCS); REPORT_DATE=18 September 2012; VALUE_TEXT=1000; DOSE=_____________________________________________________ 25 The clinical symptoms reported for two females in the high dose group are considered adverse, as there were similar clinical symptoms observed in the high dose group at the same dose in the 90-day repeated dose toxicity study [7].; EFFECT=_____________________________________________________ 25 The clinical symptoms reported for two females in the high dose group are considered adverse, as there were similar clinical symptoms observed in the high dose group at the same dose in the 90-day repeated dose toxicity study [7]. Therefore, the NOAEL for maternal toxicity is considered 300 mg/kg bw/day. Lumbar vertebrae absent in one foetus of the high dose group were considered an incidental malformation by the study authors but not treatment-related. The NOAEL for the developmental toxicity is considered 1000 mg/kg bw/day. 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 3.3.13. Safety evaluation (including calculation of the MoS) CALCULATION OF THE MARGIN OF SAFETY Oxidative conditions; CITATION_NUMBERS=[]; DETAILS_JSON={"cas_number":"857035-95-1","citation":"","dose":"_____________________________________________________ 25 The clinical symptoms reported for two females in the high dose group are considered adverse, as there were similar clinical symptoms observed in the high dose group at the same dose in the 90-day repeated dose toxicity study [7].","duration":"90-day","effect":"_____________________________________________________ 25 The clinical symptoms reported for two females in the high dose group are considered adverse, as there were similar clinical symptoms observed in the high dose group at the same dose in the 90-day repeated dose toxicity study [7]. Therefore, the NOAEL for maternal toxicity is considered 300 mg/kg bw/day. Lumbar vertebrae absent in one foetus of the high dose group were considered an incidental malformation by the study authors but not treatment-related. The NOAEL for the developmental toxicity is considered 1000 mg/kg bw/day. 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 3.3.13. Safety evaluation (including calculation of the MoS) CALCULATION OF THE MARGIN OF SAFETY Oxidative conditions","endpoint":"repeated dose toxicity","ingredient":"2,3-Diaminodihydropyrazolopyrazolone dimethosulfonate (INCI-name)","loael_value":"","noael_unit":"mg/kg bw/day","noael_value":"1000","page":25,"route":"","species":"human","study_id":"sccs_o_105_noael_007"}
openFDA substances 4 endpoints
Source Endpoint Type Value Unit Species Route Duration Study Type Reference
openFDA substances FDA UNII substance identifier S409QAZ004 UNII - - - chemical {"approval_status":null,"molecular_formula":"C6H10N4O.2CH4O3S","source_table":"substance_identifiers_fda","substance_class":"chemical","unii_code":"S409QAZ004"}
openFDA substances FDA UNII substance identifier S409QAZ004 UNII - - - chemical {"approval_status":null,"molecular_formula":"C6H10N4O.2CH4O3S","source_table":"substance_identifiers_fda","substance_class":"chemical","unii_code":"S409QAZ004"}
openFDA substances FDA UNII substance identifier S409QAZ004 UNII - - - chemical {"approval_status":null,"molecular_formula":"C6H10N4O.2CH4O3S","source_table":"substance_identifiers_fda","substance_class":"chemical","unii_code":"S409QAZ004"}
openFDA substances FDA UNII substance identifier S409QAZ004 UNII - - - chemical {"approval_status":null,"molecular_formula":"C6H10N4O.2CH4O3S","source_table":"substance_identifiers_fda","substance_class":"chemical","unii_code":"S409QAZ004"}