NOAEL Studies Active Ingredient

Climbazole NOAEL Studies

INCI: CLIMBAZOLE

CAS: 38083-17-9

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

COSMOS_DB 1 endpoint
Source Endpoint Type Value Unit Species Route Duration Study Type Reference
COSMOS_DB LOAEL 5 mg/kg bw/day rat oral 90 day Subchronic SCCP; Bayer AG, Institute for Toxicology. BAY e 6975 - Subchronic Toxicological Studies onRats (Treatment through Stomach Tube for 3 Months). Pharma Report No. 7210.Wuppertal
ECHA_REACH_reach_study_results_dossiers_23-05-2023.zip 18 endpoints
Source Endpoint Type Value Unit Species Route Duration Study Type Reference
ECHA_REACH_reach_study_results_dossiers_23-05-2023.zip LOAEL 50 mg/kg bw/day rat oral: gavage - short-term repeated dose toxicity: oral dossier=1364b88b-e4e8-47e3-8a26-48e63ddc73db.i6z; document=c7b14064-75a6-48d1-b23a-b3368dbf37dc_1364b88b-e4e8-47e3-8a26-48e63ddc73db.i6d; document_key=c7b14064-75a6-48d1-b23a-b3368dbf37dc/1364b88b-e4e8-47e3-8a26-48e63ddc73db; document_subtype=RepeatedDoseToxicityOral; literature=Name=Unnamed; ReferenceYear=1975; ReportDate=1975-01-08; basis=other:; key_result=false; entry_uuid=347f7c01-47a8-447b-af8b-a20ea22a91d9
ECHA_REACH_reach_study_results_dossiers_23-05-2023.zip LOAEL 50 mg/kg bw/day rat oral: gavage - short-term repeated dose toxicity: oral dossier=1364b88b-e4e8-47e3-8a26-48e63ddc73db.i6z; document=c7b14064-75a6-48d1-b23a-b3368dbf37dc_1364b88b-e4e8-47e3-8a26-48e63ddc73db.i6d; document_key=c7b14064-75a6-48d1-b23a-b3368dbf37dc/1364b88b-e4e8-47e3-8a26-48e63ddc73db; document_subtype=RepeatedDoseToxicityOral; literature=Name=Unnamed; ReferenceYear=1975; ReportDate=1975-01-08; basis=other:; key_result=false; entry_uuid=347f7c01-47a8-447b-af8b-a20ea22a91d9
ECHA_REACH_reach_study_results_dossiers_23-05-2023.zip LOAEL 50 mg/kg bw/day rat oral: gavage - short-term repeated dose toxicity: oral dossier=1364b88b-e4e8-47e3-8a26-48e63ddc73db.i6z; document=c7b14064-75a6-48d1-b23a-b3368dbf37dc_1364b88b-e4e8-47e3-8a26-48e63ddc73db.i6d; document_key=c7b14064-75a6-48d1-b23a-b3368dbf37dc/1364b88b-e4e8-47e3-8a26-48e63ddc73db; document_subtype=RepeatedDoseToxicityOral; literature=Name=Unnamed; ReferenceYear=1975; ReportDate=1975-01-08; basis=other:; key_result=false; entry_uuid=347f7c01-47a8-447b-af8b-a20ea22a91d9
ECHA_REACH_reach_study_results_dossiers_23-05-2023.zip NOAEL 45 mg/kg bw/day rat oral: gavage - sub-chronic toxicity: oral dossier=1364b88b-e4e8-47e3-8a26-48e63ddc73db.i6z; document=656ca33a-b090-4d36-91ec-9e5e439c3f05_1364b88b-e4e8-47e3-8a26-48e63ddc73db.i6d; document_key=656ca33a-b090-4d36-91ec-9e5e439c3f05/1364b88b-e4e8-47e3-8a26-48e63ddc73db; document_subtype=RepeatedDoseToxicityOral; literature=Name=Unnamed; ReferenceYear=1978; ReportDate=1978-01-09; basis=other:; key_result=false; entry_uuid=3d50ab4c-ba4a-4134-a443-3d9ee24e2507
ECHA_REACH_reach_study_results_dossiers_23-05-2023.zip NOAEL 60 mg/kg bw/day rabbit oral: gavage - developmental toxicity dossier=1364b88b-e4e8-47e3-8a26-48e63ddc73db.i6z; document=6fbbc375-0437-4e3f-a4dd-ad9c7dc41d51_1364b88b-e4e8-47e3-8a26-48e63ddc73db.i6d; document_key=6fbbc375-0437-4e3f-a4dd-ad9c7dc41d51/1364b88b-e4e8-47e3-8a26-48e63ddc73db; document_subtype=DevelopmentalToxicityTeratogenicity; literature=Name=Unnamed; ReferenceYear=2001; ReportDate=2001-11-29; basis=other:; key_result=true; entry_uuid=7f7aae77-dc16-469b-bf09-263899d1a356
ECHA_REACH_reach_study_results_dossiers_23-05-2023.zip NOAEL 100 mg/kg bw/day rat oral: gavage - fertility, other dossier=1364b88b-e4e8-47e3-8a26-48e63ddc73db.i6z; document=010dacb1-8c3c-421c-b164-30e8b91476bd_1364b88b-e4e8-47e3-8a26-48e63ddc73db.i6d; document_key=010dacb1-8c3c-421c-b164-30e8b91476bd/1364b88b-e4e8-47e3-8a26-48e63ddc73db; document_subtype=ToxicityReproduction; literature=Name=Unnamed; ReferenceYear=1979; ReportDate=1979-03-02; basis=other:; key_result=true; entry_uuid=09d64b10-8f17-446b-ac77-35048c03cc32
ECHA_REACH_reach_study_results_dossiers_23-05-2023.zip NOAEL 36 mg/kg bw/day rat oral: gavage - fertility, other dossier=1364b88b-e4e8-47e3-8a26-48e63ddc73db.i6z; document=010dacb1-8c3c-421c-b164-30e8b91476bd_1364b88b-e4e8-47e3-8a26-48e63ddc73db.i6d; document_key=010dacb1-8c3c-421c-b164-30e8b91476bd/1364b88b-e4e8-47e3-8a26-48e63ddc73db; document_subtype=ToxicityReproduction; literature=Name=Unnamed; ReferenceYear=1979; ReportDate=1979-03-02; basis=clinical signs; key_result=true; entry_uuid=96d71232-6985-4eba-9fc1-5fc64a3bcbb0
ECHA_REACH_reach_study_results_dossiers_23-05-2023.zip NOAEL 45 mg/kg bw/day rat oral: gavage - sub-chronic toxicity: oral dossier=1364b88b-e4e8-47e3-8a26-48e63ddc73db.i6z; document=656ca33a-b090-4d36-91ec-9e5e439c3f05_1364b88b-e4e8-47e3-8a26-48e63ddc73db.i6d; document_key=656ca33a-b090-4d36-91ec-9e5e439c3f05/1364b88b-e4e8-47e3-8a26-48e63ddc73db; document_subtype=RepeatedDoseToxicityOral; literature=Name=Unnamed; ReferenceYear=1978; ReportDate=1978-01-09; basis=other:; key_result=false; entry_uuid=3d50ab4c-ba4a-4134-a443-3d9ee24e2507
ECHA_REACH_reach_study_results_dossiers_23-05-2023.zip NOAEL 60 mg/kg bw/day rabbit oral: gavage - developmental toxicity dossier=1364b88b-e4e8-47e3-8a26-48e63ddc73db.i6z; document=6fbbc375-0437-4e3f-a4dd-ad9c7dc41d51_1364b88b-e4e8-47e3-8a26-48e63ddc73db.i6d; document_key=6fbbc375-0437-4e3f-a4dd-ad9c7dc41d51/1364b88b-e4e8-47e3-8a26-48e63ddc73db; document_subtype=DevelopmentalToxicityTeratogenicity; literature=Name=Unnamed; ReferenceYear=2001; ReportDate=2001-11-29; basis=other:; key_result=true; entry_uuid=7f7aae77-dc16-469b-bf09-263899d1a356
ECHA_REACH_reach_study_results_dossiers_23-05-2023.zip NOAEL 100 mg/kg bw/day rat oral: gavage - fertility, other dossier=1364b88b-e4e8-47e3-8a26-48e63ddc73db.i6z; document=010dacb1-8c3c-421c-b164-30e8b91476bd_1364b88b-e4e8-47e3-8a26-48e63ddc73db.i6d; document_key=010dacb1-8c3c-421c-b164-30e8b91476bd/1364b88b-e4e8-47e3-8a26-48e63ddc73db; document_subtype=ToxicityReproduction; literature=Name=Unnamed; ReferenceYear=1979; ReportDate=1979-03-02; basis=other:; key_result=true; entry_uuid=09d64b10-8f17-446b-ac77-35048c03cc32
ECHA_REACH_reach_study_results_dossiers_23-05-2023.zip NOAEL 36 mg/kg bw/day rat oral: gavage - fertility, other dossier=1364b88b-e4e8-47e3-8a26-48e63ddc73db.i6z; document=010dacb1-8c3c-421c-b164-30e8b91476bd_1364b88b-e4e8-47e3-8a26-48e63ddc73db.i6d; document_key=010dacb1-8c3c-421c-b164-30e8b91476bd/1364b88b-e4e8-47e3-8a26-48e63ddc73db; document_subtype=ToxicityReproduction; literature=Name=Unnamed; ReferenceYear=1979; ReportDate=1979-03-02; basis=clinical signs; key_result=true; entry_uuid=96d71232-6985-4eba-9fc1-5fc64a3bcbb0
ECHA_REACH_reach_study_results_dossiers_23-05-2023.zip NOAEL 45 mg/kg bw/day rat oral: gavage - sub-chronic toxicity: oral dossier=1364b88b-e4e8-47e3-8a26-48e63ddc73db.i6z; document=656ca33a-b090-4d36-91ec-9e5e439c3f05_1364b88b-e4e8-47e3-8a26-48e63ddc73db.i6d; document_key=656ca33a-b090-4d36-91ec-9e5e439c3f05/1364b88b-e4e8-47e3-8a26-48e63ddc73db; document_subtype=RepeatedDoseToxicityOral; literature=Name=Unnamed; ReferenceYear=1978; ReportDate=1978-01-09; basis=other:; key_result=false; entry_uuid=3d50ab4c-ba4a-4134-a443-3d9ee24e2507
ECHA_REACH_reach_study_results_dossiers_23-05-2023.zip NOAEL 60 mg/kg bw/day rabbit oral: gavage - developmental toxicity dossier=1364b88b-e4e8-47e3-8a26-48e63ddc73db.i6z; document=6fbbc375-0437-4e3f-a4dd-ad9c7dc41d51_1364b88b-e4e8-47e3-8a26-48e63ddc73db.i6d; document_key=6fbbc375-0437-4e3f-a4dd-ad9c7dc41d51/1364b88b-e4e8-47e3-8a26-48e63ddc73db; document_subtype=DevelopmentalToxicityTeratogenicity; literature=Name=Unnamed; ReferenceYear=2001; ReportDate=2001-11-29; basis=other:; key_result=true; entry_uuid=7f7aae77-dc16-469b-bf09-263899d1a356
ECHA_REACH_reach_study_results_dossiers_23-05-2023.zip NOAEL 100 mg/kg bw/day rat oral: gavage - fertility, other dossier=1364b88b-e4e8-47e3-8a26-48e63ddc73db.i6z; document=010dacb1-8c3c-421c-b164-30e8b91476bd_1364b88b-e4e8-47e3-8a26-48e63ddc73db.i6d; document_key=010dacb1-8c3c-421c-b164-30e8b91476bd/1364b88b-e4e8-47e3-8a26-48e63ddc73db; document_subtype=ToxicityReproduction; literature=Name=Unnamed; ReferenceYear=1979; ReportDate=1979-03-02; basis=other:; key_result=true; entry_uuid=09d64b10-8f17-446b-ac77-35048c03cc32
ECHA_REACH_reach_study_results_dossiers_23-05-2023.zip NOAEL 36 mg/kg bw/day rat oral: gavage - fertility, other dossier=1364b88b-e4e8-47e3-8a26-48e63ddc73db.i6z; document=010dacb1-8c3c-421c-b164-30e8b91476bd_1364b88b-e4e8-47e3-8a26-48e63ddc73db.i6d; document_key=010dacb1-8c3c-421c-b164-30e8b91476bd/1364b88b-e4e8-47e3-8a26-48e63ddc73db; document_subtype=ToxicityReproduction; literature=Name=Unnamed; ReferenceYear=1979; ReportDate=1979-03-02; basis=clinical signs; key_result=true; entry_uuid=96d71232-6985-4eba-9fc1-5fc64a3bcbb0
ECHA_REACH_reach_study_results_dossiers_23-05-2023.zip NOEL 15 mg/kg bw/day rabbit oral: gavage - developmental toxicity dossier=1364b88b-e4e8-47e3-8a26-48e63ddc73db.i6z; document=6fbbc375-0437-4e3f-a4dd-ad9c7dc41d51_1364b88b-e4e8-47e3-8a26-48e63ddc73db.i6d; document_key=6fbbc375-0437-4e3f-a4dd-ad9c7dc41d51/1364b88b-e4e8-47e3-8a26-48e63ddc73db; document_subtype=DevelopmentalToxicityTeratogenicity; literature=Name=Unnamed; ReferenceYear=2001; ReportDate=2001-11-29; basis=other:; key_result=true; entry_uuid=0576cabd-6339-448e-9e19-5f230c015c48
ECHA_REACH_reach_study_results_dossiers_23-05-2023.zip NOEL 15 mg/kg bw/day rabbit oral: gavage - developmental toxicity dossier=1364b88b-e4e8-47e3-8a26-48e63ddc73db.i6z; document=6fbbc375-0437-4e3f-a4dd-ad9c7dc41d51_1364b88b-e4e8-47e3-8a26-48e63ddc73db.i6d; document_key=6fbbc375-0437-4e3f-a4dd-ad9c7dc41d51/1364b88b-e4e8-47e3-8a26-48e63ddc73db; document_subtype=DevelopmentalToxicityTeratogenicity; literature=Name=Unnamed; ReferenceYear=2001; ReportDate=2001-11-29; basis=other:; key_result=true; entry_uuid=0576cabd-6339-448e-9e19-5f230c015c48
ECHA_REACH_reach_study_results_dossiers_23-05-2023.zip NOEL 15 mg/kg bw/day rabbit oral: gavage - developmental toxicity dossier=1364b88b-e4e8-47e3-8a26-48e63ddc73db.i6z; document=6fbbc375-0437-4e3f-a4dd-ad9c7dc41d51_1364b88b-e4e8-47e3-8a26-48e63ddc73db.i6d; document_key=6fbbc375-0437-4e3f-a4dd-ad9c7dc41d51/1364b88b-e4e8-47e3-8a26-48e63ddc73db; document_subtype=DevelopmentalToxicityTeratogenicity; literature=Name=Unnamed; ReferenceYear=2001; ReportDate=2001-11-29; basis=other:; key_result=true; entry_uuid=0576cabd-6339-448e-9e19-5f230c015c48
NTP_ICE_acute_oral 1 endpoint
Source Endpoint Type Value Unit Species Route Duration Study Type Reference
NTP_ICE_acute_oral LD50 =400 mg/kg bw Rat oral acute Rat Acute Oral Toxicity NLM ChemIDplus TEST (undated); record_id=acute_oral_6114; row=10943; data_type=In Vivo; mixture=Chemical; chemical_name=Climbazole; preferred_name=Climbazole; dtxsid=DTXSID6046555; url=https://chem.nlm.nih.gov/chemidplus/; url_comptox=https://comptox.epa.gov/dashboard/chemical/details/DTXSID6046555; source_file=acute_oral.xlsx
SCCS_vision_codex 65 endpoints
Source Endpoint Type Value Unit Species Route Duration Study Type Reference
SCCS_vision_codex DERMAL_ABSORPTION =1 % - dermal - in vitro {"absorption_percent":"1%","basis":"Guideline: in vitro percutaneous absorption study, 1984 internal protocol Tissue: human abdominal skin Method: diffusion chamber Test substance: Ceox® = shampoo containing 1% Climbazole (purity not stated) Batch no: not stated Concentrations: Ceox® dissolved 1:2 or 1:10 with water Amount applied: 0.5 ml/4.91 cm² No. of chambers: 6 GLP: no information (performed in 1984)","page":11,"pdf":"sccp_o_027.pdf","row_type":"dermal_absorption_study"}
SCCS_vision_codex DERMAL_ABSORPTION =0.04 % - dermal - Dermal absorption {"absorption_percent":"0.04%; 0.09%","basis":"Conclusion The study was not conducted according to the current dermal absorption guidelines. No measurements have been performed in the skin. The diluted formulation was applied at a dosage level of 0.5ml/4.91cm², corresponding to ± 102 mg/cm². In a finite dose experiment 2-5 mg/cm² is recommended. Therefore, the calculated percentages of 0.04% to 0.09% are not acceptable. There was no dose-dependency in the penetration rates of the tests under occlusion. Many other shortcomings can be noted.","page":12,"pdf":"sccp_o_027.pdf","row_type":"dermal_absorption_study"}
SCCS_vision_codex DERMAL_ABSORPTION =2.3 % - dermal - Dermal absorption {"absorption_percent":"2.3%","basis":"* BAY g 5919 = major metabolite of Climbazole : None of the above studies were performed according to an existing guideline. Their descriptions are very brief and no control groups have been included, which makes the results difficult to assess. Nevertheless, it cannot be denied that Climbazole and its major metabolite are measured in blood plasma and urine after application of a shampoo under in-use (mimicking) conditions. This is a clear indication that percutaneous absorption does take place. One of the studies mentions an absorption value for Climbazole of 2.3%. Ref.: 20, 21, 23, 68","citation":"Ref.: 20, 21, 23, 68","page":13,"pdf":"sccp_o_027.pdf","row_type":"dermal_absorption_study"}
SCCS_vision_codex DERMAL_ABSORPTION =1 % - dermal - in vitro {"absorption_percent":"1%","basis":"Guideline: in vitro percutaneous absorption study, 1984 internal protocol Tissue: human abdominal skin Method: diffusion chamber Test substance: Ceox® = shampoo containing 1% Climbazole (purity not stated) Batch no: not stated Concentrations: Ceox® dissolved 1:2 or 1:10 with water Amount applied: 0.5 ml/4.91 cm² No. of chambers: 6 GLP: no information (performed in 1984)","page":11,"pdf":"sccp_o_027.pdf","row_type":"dermal_absorption_study"}
SCCS_vision_codex DERMAL_ABSORPTION =0.04 % - dermal - Dermal absorption {"absorption_percent":"0.04%; 0.09%","basis":"Conclusion The study was not conducted according to the current dermal absorption guidelines. No measurements have been performed in the skin. The diluted formulation was applied at a dosage level of 0.5ml/4.91cm², corresponding to ± 102 mg/cm². In a finite dose experiment 2-5 mg/cm² is recommended. Therefore, the calculated percentages of 0.04% to 0.09% are not acceptable. There was no dose-dependency in the penetration rates of the tests under occlusion. Many other shortcomings can be noted.","page":12,"pdf":"sccp_o_027.pdf","row_type":"dermal_absorption_study"}
SCCS_vision_codex DERMAL_ABSORPTION =2.3 % - dermal - Dermal absorption {"absorption_percent":"2.3%","basis":"* BAY g 5919 = major metabolite of Climbazole : None of the above studies were performed according to an existing guideline. Their descriptions are very brief and no control groups have been included, which makes the results difficult to assess. Nevertheless, it cannot be denied that Climbazole and its major metabolite are measured in blood plasma and urine after application of a shampoo under in-use (mimicking) conditions. This is a clear indication that percutaneous absorption does take place. One of the studies mentions an absorption value for Climbazole of 2.3%. Ref.: 20, 21, 23, 68","citation":"Ref.: 20, 21, 23, 68","page":13,"pdf":"sccp_o_027.pdf","row_type":"dermal_absorption_study"}
SCCS_vision_codex DERMAL_ABSORPTION =1 % - dermal - in vitro {"absorption_percent":"1%","basis":"Guideline: in vitro percutaneous absorption study, 1984 internal protocol Tissue: human abdominal skin Method: diffusion chamber Test substance: Ceox® = shampoo containing 1% Climbazole (purity not stated) Batch no: not stated Concentrations: Ceox® dissolved 1:2 or 1:10 with water Amount applied: 0.5 ml/4.91 cm² No. of chambers: 6 GLP: no information (performed in 1984)","page":11,"pdf":"sccp_o_027.pdf","row_type":"dermal_absorption_study"}
SCCS_vision_codex DERMAL_ABSORPTION =0.04 % - dermal - Dermal absorption {"absorption_percent":"0.04%; 0.09%","basis":"Conclusion The study was not conducted according to the current dermal absorption guidelines. No measurements have been performed in the skin. The diluted formulation was applied at a dosage level of 0.5ml/4.91cm², corresponding to ± 102 mg/cm². In a finite dose experiment 2-5 mg/cm² is recommended. Therefore, the calculated percentages of 0.04% to 0.09% are not acceptable. There was no dose-dependency in the penetration rates of the tests under occlusion. Many other shortcomings can be noted.","page":12,"pdf":"sccp_o_027.pdf","row_type":"dermal_absorption_study"}
SCCS_vision_codex DERMAL_ABSORPTION =2.3 % - dermal - Dermal absorption {"absorption_percent":"2.3%","basis":"* BAY g 5919 = major metabolite of Climbazole : None of the above studies were performed according to an existing guideline. Their descriptions are very brief and no control groups have been included, which makes the results difficult to assess. Nevertheless, it cannot be denied that Climbazole and its major metabolite are measured in blood plasma and urine after application of a shampoo under in-use (mimicking) conditions. This is a clear indication that percutaneous absorption does take place. One of the studies mentions an absorption value for Climbazole of 2.3%. Ref.: 20, 21, 23, 68","citation":"Ref.: 20, 21, 23, 68","page":13,"pdf":"sccp_o_027.pdf","row_type":"dermal_absorption_study"}
SCCS_vision_codex NOAEL =50 mg/kg bw/day rat oral sub-chronic repeated dose toxicity {"citation":"Ref.: 30 42-day oral toxicity study with the dog Guideline: 42-day oral toxicity test (1974) according to guidelines at the time Species/strain: Beagle dog Group size: 2 males + 2 female","dose":"The study is acceptable as a dose-finding (pilot) experiment.","effect":"SCCP/0918/05 Opinion on Climbazole (P64) 15 Conclusion The study was neither conducted in full compliance with the respective current OECD Guideline, nor has formal adherence to GLP principles been documented and reported. However, due to the availability of detailed information on the study design and findings (including some individual animal data), limited validity in terms of scientific criteria can be assigned. The study is acceptable as a dose-finding (pilot) experiment. Its results indicate that the NOAEL for Climbazole following repeated (sub-chronic) daily per oral dosing in the rat is lower than 50 mg/kg bw/day. The observed adverse effects were blood biochemical changes and morphological organ damage in the liver. Ref.: 30 42-day oral toxicity study with the dog Guideline: 42-day oral toxicity test (1974) according to guidelines at the time Species/strain: Beagle dog Group size: 2 males + 2 females Test substance: BAY e 6975 (Climbazole, purity not stated) Batch no.: 483751 Dose levels: 0, 100 mg/kg bw/day we","page":15,"pdf":"sccp_o_027.pdf","row_type":"noael_study","study_id":"sccp_o_027_noael_001"}
SCCS_vision_codex NOAEL =5 mg/kg bw/day rat oral 13 weeks NOAEL study {"citation":"Ref.: 2 90-day oral toxicity study with the dog Guideline: 90-day oral toxicity test (1980) according to guidelines at the time Species/strain: Beagle dog Group size: 3 males + 3 females","dose":"SCCP/0918/05 Opinion on Climbazole (P64) 17 Test substance-related effects were observed following daily p.o. dosing of rats over 13 weeks at the intermediate and high dose levels (15 and 45 mg/kg bw/day).","effect":"SCCP/0918/05 Opinion on Climbazole (P64) 17 Test substance-related effects were observed following daily p.o. dosing of rats over 13 weeks at the intermediate and high dose levels (15 and 45 mg/kg bw/day). The liver was identified as target organ for the effects of Climbazole. Because the effects on the liver at 15 mg/kg bw/day (increased liver weight without histopathological evidence of toxicity, P450 induction) were not judged to be clinical relevant, this dose is regarded as a NOAEL by the experimenters. Conclusion Viewing the absence of the full raw data package, it appears to be safer to use the NOEL value of 5 mg/kg bw/day for the calculation of the MoS of Climbazole. Ref.: 2 90-day oral toxicity study with the dog Guideline: 90-day oral toxicity test (1980) according to guidelines at the time Species/strain: Beagle dog Group size: 3 males + 3 females Test substance: BAY e 6975 (Climbazole, purity not stated) Batch no.: 483751 Dose levels: 0, 5, 10, 20 mg/kg bw/day Route: oral; capsule","page":17,"pdf":"sccp_o_027.pdf","row_type":"noael_study","study_id":"sccp_o_027_noael_003"}
SCCS_vision_codex NOAEL =20 mg/kg bw/day dog - sub-chronic repeated dose toxicity {"citation":"Ref.: 3 3","dose":"Based on the reported study results, the laboratory proposes to use the highest tested dose of 20 mg/kg bw/day as the NOAEL in this sub-chronic peroral toxicity study in dogs.","effect":"Conclusion The study was neither conducted in full compliance with the respective current OECD Guideline, nor has formal adherence to GLP principles been documented and reported. However, due to the availability of detailed information on the study design and findings (including some individual animal data), satisfactory validity in terms of scientific criteria can be assigned to this experiment. Based on the reported study results, the laboratory proposes to use the highest tested dose of 20 mg/kg bw/day as the NOAEL in this sub-chronic peroral toxicity study in dogs. The only test substance-related effects observed exclusively in the high dose group were not considered as adverse effects but rather as signs of adaptive changes indicating increased metabolic activity. Viewing the absence of the full raw data package, it appears to be safer to take into account the NOEL value of 10 mg/kg bw/day. Ref.: 3 3.3.5.3. Chronic (> 12 months) toxicity No chronic toxicity studies have been conducted with Climbazole. 3.3.6. Mutagenicit","page":18,"pdf":"sccp_o_027.pdf","row_type":"noael_study","study_id":"sccp_o_027_noael_005"}
SCCS_vision_codex NOAEL =10 mg/kg bw/day dog - sub-chronic repeated dose toxicity {"citation":"Ref.: 3 3","dose":"Based on the reported study results, the laboratory proposes to use the highest tested dose of 20 mg/kg bw/day as the NOAEL in this sub-chronic peroral toxicity study in dogs.","effect":"teria can be assigned to this experiment. Based on the reported study results, the laboratory proposes to use the highest tested dose of 20 mg/kg bw/day as the NOAEL in this sub-chronic peroral toxicity study in dogs. The only test substance-related effects observed exclusively in the high dose group were not considered as adverse effects but rather as signs of adaptive changes indicating increased metabolic activity. Viewing the absence of the full raw data package, it appears to be safer to take into account the NOEL value of 10 mg/kg bw/day. Ref.: 3 3.3.5.3. Chronic (> 12 months) toxicity No chronic toxicity studies have been conducted with Climbazole. 3.3.6. Mutagenicity / Genotoxicity 3.3.6.1. Mutagenicity / Genotoxicity in vitro Ames test 1 (parent compound) Guideline: Ames test (1977) according to guidelines at the time Species/strain: Salmonella typhimurium, TA100, TA1537, TA98 Replicates: 2 Test substance: BAY e 6975 (Climbazole, purity not stated) Batch no.: 323568 Concentrations: 0, 3.15, 10, 31.5, 100, 315, 100","page":18,"pdf":"sccp_o_027.pdf","row_type":"noael_study","study_id":"sccp_o_027_noael_006"}
SCCS_vision_codex NOAEL =7.2 mg/kg bw/day rat oral - NOAEL study {"citation":"Ref.: 87 3","dose":"At the 36 mg/kg bw/day treatment level, the female rats exhibited slight-to-moderate toxicity during the initial stages of treatment with no observable effects on estrous or stillbirths.","effect":"he initial stages of treatment which caused disruption of the estrous cycles and an increased number of stillbirths. At the 36 mg/kg bw/day treatment level, the female rats exhibited slight-to-moderate toxicity during the initial stages of treatment with no observable effects on estrous or stillbirths. Embryotoxicity observed at 36 and 100 mg/kg bw/day consisted in decreased numbers of life pups at birth and was judged to be a secondary effect to maternal toxicity. Viewing the lack of full raw data, the following NOAEL values are proposed: NOAEL (maternal toxicity) = 7.2 mg/kg bw/day, NOAEL (embryotoxicity) = 36 mg/kg bw/day. Ref.: 87 3.3.8.2. Teratogenicity Teratogenicity study in the rabbit Guideline: OECD guideline no. 414 (adopted 22nd January 2001) Date of test : May-July 2001 Species/strain: Chinchilla rabbit Group size: 24 mated females Test substance: HR 00/600306 (Climbazole, purity min. 98%) Batch no.: 20072001 Dose levels: 0, 15, 30, 60 mg/kg bw/day Route: oral; gavage Exposure: days 6 through 27 of pregnancy GLP:","page":24,"pdf":"sccp_o_027.pdf","row_type":"noael_study","study_id":"sccp_o_027_noael_007"}
SCCS_vision_codex NOAEL =30 mg/kg bw/day rat oral - developmental toxicity {"citation":"Ref.: 17 Teratogenicity study in the rat (1) Guideline: teratogenicity study (1981) according to guidelines at the time Species/strain: BAY: FB30 rat Group size: 25 inseminated females T","dose":"the highest dose group.","effect":"the highest dose group. This difference in sex ratio was not considered to be test item-related. Examination of viscera, skeleton, and cartilage revealed no Climbazole-related foetal abnormalities. Conclusion No teratogenic effects were observed in this study with rabbits. Maternal toxicity (alopecia, reduced weight gain) was seen at 30 and 60 mg/kg bw/day. Embryotoxic effects (increased post- implantational losses) seen in the highest dose group are considered to be secondary to the effects on dams. The proposed NOAEL (embryotoxicity) is 30 mg/kg bw/day. Based on maternal toxicity at the two higher doses, 15 mg/kg bw/day is considered a NOAEL for maternal toxicity. Ref.: 17 Teratogenicity study in the rat (1) Guideline: teratogenicity study (1981) according to guidelines at the time Species/strain: BAY: FB30 rat Group size: 25 inseminated females Test substance: BAY e 6975 (Climbazole, purity not stated) Batch no.: 570327 Dose levels: 0, 10, 30, 100 mg/kg bw/day Route: oral; gavage Exposure: days 6 to 15 of pregnancy, inclusi","page":25,"pdf":"sccp_o_027.pdf","row_type":"noael_study","study_id":"sccp_o_027_noael_010"}
SCCS_vision_codex NOAEL =15 mg/kg bw/day rat oral 6 to day developmental toxicity {"citation":"Ref.: 17 Teratogenicity study in the rat (1) Guideline: teratogenicity study (1981) according to guidelines at the time Species/strain: BAY: FB30 rat Group size: 25 inseminated females T","dose":"Maternal toxicity (alopecia, reduced weight gain) was seen at 30 and 60 mg/kg bw/day.","effect":"on, and cartilage revealed no Climbazole-related foetal abnormalities. Conclusion No teratogenic effects were observed in this study with rabbits. Maternal toxicity (alopecia, reduced weight gain) was seen at 30 and 60 mg/kg bw/day. Embryotoxic effects (increased post- implantational losses) seen in the highest dose group are considered to be secondary to the effects on dams. The proposed NOAEL (embryotoxicity) is 30 mg/kg bw/day. Based on maternal toxicity at the two higher doses, 15 mg/kg bw/day is considered a NOAEL for maternal toxicity. Ref.: 17 Teratogenicity study in the rat (1) Guideline: teratogenicity study (1981) according to guidelines at the time Species/strain: BAY: FB30 rat Group size: 25 inseminated females Test substance: BAY e 6975 (Climbazole, purity not stated) Batch no.: 570327 Dose levels: 0, 10, 30, 100 mg/kg bw/day Route: oral; gavage Exposure: days 6 to 15 of pregnancy, inclusive GLP: no information (test performed in 1981, prior to GLP regulations) Climbazole was administered daily from day 6 to day","page":25,"pdf":"sccp_o_027.pdf","row_type":"noael_study","study_id":"sccp_o_027_noael_011"}
SCCS_vision_codex NOAEL =10 mg/kg rat - - developmental toxicity {"citation":"Ref.: 16 Teratogenicity study in the rat (2) Guideline: teratogenicity study (1979) according to guidelines at the time Species/strain: Charles River CD® rat Group size: 25 inseminated f","dose":"The laboratory concludes that no signs of teratogenic effects were seen in this teratogenicity study with rats with applied doses of 10 to 100 mg/kg during gestation days 6 through 15.","effect":"ticular study appear to be reliable. Conclusion The study was neither conducted in full compliance with the respective current OECD Guideline, nor has formal adherence to GLP principles been documented and reported. This makes the results difficult to interpret, especially in the case of such a specialised area as teratogenicity. The laboratory concludes that no signs of teratogenic effects were seen in this teratogenicity study with rats with applied doses of 10 to 100 mg/kg during gestation days 6 through 15. A NOAEL of 10 mg/kg has been identified for maternal toxicity. Embryotoxic effects were observed at 100 mg/kg and were judged to be secondary effects to the maternal toxicity. Ref.: 16 Teratogenicity study in the rat (2) Guideline: teratogenicity study (1979) according to guidelines at the time Species/strain: Charles River CD® rat Group size: 25 inseminated females Test substance: Compound No. 34054 (Climbazole, purity not stated)","page":26,"pdf":"sccp_o_027.pdf","row_type":"noael_study","study_id":"sccp_o_027_noael_012"}
SCCS_vision_codex NOAEL =7.2 mg/kg rat - - developmental toxicity {"citation":"Ref.: 85 Additional studies The dossier contains a teratogenicity study from 1977, in which only one dosage level (100 mg/kg bw/day) was tested","dose":"The authors conclude that skeletal variations have been observed in pups at maternal doses of 36 and 100 mg/kg bw/day.","effect":"velopmental toxicity study was neither conducted in full compliance with the respective current OECD Guideline, nor has formal adherence to GLP principles been documented and reported. The lack of the full raw data package makes the results difficult to interpret. The authors conclude that skeletal variations have been observed in pups at maternal doses of 36 and 100 mg/kg bw/day. Maternal toxicity was obvious at 36 and 100 mg/kg bw/day, 4 dams died at the highest dose. The lowest dose (7.2mg/kg) was found to be a NOAEL. There were no clear- cut indications of specific teratogenic effects at any dose level. Ref.: 85 Additional studies The dossier contains a teratogenicity study from 1977, in which only one dosage level (100 mg/kg bw/day) was tested. Viewing the restricted aim (dose-range finding study) and the age of the study, it is not discussed in detail. Ref.: 31 Finally, a so-called \"peri-/postnatal toxicity study\" is provided, in which 20 inseminated female rats were administered Compound N°34054 (Climbazole, purity not","page":28,"pdf":"sccp_o_027.pdf","row_type":"noael_study","study_id":"sccp_o_027_noael_013"}
SCCS_vision_codex NOAEL =5 mg/kg/day rat oral 90d developmental toxicity {"dose":"Nevertheless, based on the available information, a cautious NOEL-value of 5 mg/kg/day can be deduced from the 90d oral study with the rat.","effect":"te were measured in blood plasma and urine. Therefore, the absorption value for the calculation of the MoS for Climbazole will be considered 100% until sound dermal absorption data are provided. 9. With regard to long term toxicity studies : The dossier clearly suffers from the age of the studies. Nearly all of them have been performed between 1975 and 1983, before GLP-regulations were in place. The descriptions are brief and the raw data are incomplete. Nevertheless, based on the available information, a cautious NOEL-value of 5 mg/kg/day can be deduced from the 90d oral study with the rat. Chronic and carcinogenicity studies are not available. 10. With regard to the teratogenic effects of the substance, a relatively recent study (2001) provides a NOAEL (embryotoxicity) of 30 mg/kg bw/day and a NOAEL (maternal toxicity) of 15 mg/kg bw/day. 11. With regard to the mutagenicity/genotoxicity data The presented tests are old and have not been performed according to recent guidelines. They all show negative results. Due to the lack o","page":33,"pdf":"sccp_o_027.pdf","row_type":"noael_study","study_id":"sccp_o_027_noael_014"}
SCCS_vision_codex NOAEL =50 mg/kg bw/day rat oral sub-chronic repeated dose toxicity {"citation":"Ref.: 30 42-day oral toxicity study with the dog Guideline: 42-day oral toxicity test (1974) according to guidelines at the time Species/strain: Beagle dog Group size: 2 males + 2 female","dose":"The study is acceptable as a dose-finding (pilot) experiment.","effect":"SCCP/0918/05 Opinion on Climbazole (P64) 15 Conclusion The study was neither conducted in full compliance with the respective current OECD Guideline, nor has formal adherence to GLP principles been documented and reported. However, due to the availability of detailed information on the study design and findings (including some individual animal data), limited validity in terms of scientific criteria can be assigned. The study is acceptable as a dose-finding (pilot) experiment. Its results indicate that the NOAEL for Climbazole following repeated (sub-chronic) daily per oral dosing in the rat is lower than 50 mg/kg bw/day. The observed adverse effects were blood biochemical changes and morphological organ damage in the liver. Ref.: 30 42-day oral toxicity study with the dog Guideline: 42-day oral toxicity test (1974) according to guidelines at the time Species/strain: Beagle dog Group size: 2 males + 2 females Test substance: BAY e 6975 (Climbazole, purity not stated) Batch no.: 483751 Dose levels: 0, 100 mg/kg bw/day we","page":15,"pdf":"sccp_o_027.pdf","row_type":"noael_study","study_id":"sccp_o_027_noael_001"}
SCCS_vision_codex NOAEL =5 mg/kg bw/day rat oral 13 weeks NOAEL study {"citation":"Ref.: 2 90-day oral toxicity study with the dog Guideline: 90-day oral toxicity test (1980) according to guidelines at the time Species/strain: Beagle dog Group size: 3 males + 3 females","dose":"SCCP/0918/05 Opinion on Climbazole (P64) 17 Test substance-related effects were observed following daily p.o. dosing of rats over 13 weeks at the intermediate and high dose levels (15 and 45 mg/kg bw/day).","effect":"SCCP/0918/05 Opinion on Climbazole (P64) 17 Test substance-related effects were observed following daily p.o. dosing of rats over 13 weeks at the intermediate and high dose levels (15 and 45 mg/kg bw/day). The liver was identified as target organ for the effects of Climbazole. Because the effects on the liver at 15 mg/kg bw/day (increased liver weight without histopathological evidence of toxicity, P450 induction) were not judged to be clinical relevant, this dose is regarded as a NOAEL by the experimenters. Conclusion Viewing the absence of the full raw data package, it appears to be safer to use the NOEL value of 5 mg/kg bw/day for the calculation of the MoS of Climbazole. Ref.: 2 90-day oral toxicity study with the dog Guideline: 90-day oral toxicity test (1980) according to guidelines at the time Species/strain: Beagle dog Group size: 3 males + 3 females Test substance: BAY e 6975 (Climbazole, purity not stated) Batch no.: 483751 Dose levels: 0, 5, 10, 20 mg/kg bw/day Route: oral; capsule","page":17,"pdf":"sccp_o_027.pdf","row_type":"noael_study","study_id":"sccp_o_027_noael_003"}
SCCS_vision_codex NOAEL =20 mg/kg bw/day dog - sub-chronic repeated dose toxicity {"citation":"Ref.: 3 3","dose":"Based on the reported study results, the laboratory proposes to use the highest tested dose of 20 mg/kg bw/day as the NOAEL in this sub-chronic peroral toxicity study in dogs.","effect":"Conclusion The study was neither conducted in full compliance with the respective current OECD Guideline, nor has formal adherence to GLP principles been documented and reported. However, due to the availability of detailed information on the study design and findings (including some individual animal data), satisfactory validity in terms of scientific criteria can be assigned to this experiment. Based on the reported study results, the laboratory proposes to use the highest tested dose of 20 mg/kg bw/day as the NOAEL in this sub-chronic peroral toxicity study in dogs. The only test substance-related effects observed exclusively in the high dose group were not considered as adverse effects but rather as signs of adaptive changes indicating increased metabolic activity. Viewing the absence of the full raw data package, it appears to be safer to take into account the NOEL value of 10 mg/kg bw/day. Ref.: 3 3.3.5.3. Chronic (> 12 months) toxicity No chronic toxicity studies have been conducted with Climbazole. 3.3.6. Mutagenicit","page":18,"pdf":"sccp_o_027.pdf","row_type":"noael_study","study_id":"sccp_o_027_noael_005"}
SCCS_vision_codex NOAEL =10 mg/kg bw/day dog - sub-chronic repeated dose toxicity {"citation":"Ref.: 3 3","dose":"Based on the reported study results, the laboratory proposes to use the highest tested dose of 20 mg/kg bw/day as the NOAEL in this sub-chronic peroral toxicity study in dogs.","effect":"teria can be assigned to this experiment. Based on the reported study results, the laboratory proposes to use the highest tested dose of 20 mg/kg bw/day as the NOAEL in this sub-chronic peroral toxicity study in dogs. The only test substance-related effects observed exclusively in the high dose group were not considered as adverse effects but rather as signs of adaptive changes indicating increased metabolic activity. Viewing the absence of the full raw data package, it appears to be safer to take into account the NOEL value of 10 mg/kg bw/day. Ref.: 3 3.3.5.3. Chronic (> 12 months) toxicity No chronic toxicity studies have been conducted with Climbazole. 3.3.6. Mutagenicity / Genotoxicity 3.3.6.1. Mutagenicity / Genotoxicity in vitro Ames test 1 (parent compound) Guideline: Ames test (1977) according to guidelines at the time Species/strain: Salmonella typhimurium, TA100, TA1537, TA98 Replicates: 2 Test substance: BAY e 6975 (Climbazole, purity not stated) Batch no.: 323568 Concentrations: 0, 3.15, 10, 31.5, 100, 315, 100","page":18,"pdf":"sccp_o_027.pdf","row_type":"noael_study","study_id":"sccp_o_027_noael_006"}
SCCS_vision_codex NOAEL =7.2 mg/kg bw/day rat oral - NOAEL study {"citation":"Ref.: 87 3","dose":"At the 36 mg/kg bw/day treatment level, the female rats exhibited slight-to-moderate toxicity during the initial stages of treatment with no observable effects on estrous or stillbirths.","effect":"he initial stages of treatment which caused disruption of the estrous cycles and an increased number of stillbirths. At the 36 mg/kg bw/day treatment level, the female rats exhibited slight-to-moderate toxicity during the initial stages of treatment with no observable effects on estrous or stillbirths. Embryotoxicity observed at 36 and 100 mg/kg bw/day consisted in decreased numbers of life pups at birth and was judged to be a secondary effect to maternal toxicity. Viewing the lack of full raw data, the following NOAEL values are proposed: NOAEL (maternal toxicity) = 7.2 mg/kg bw/day, NOAEL (embryotoxicity) = 36 mg/kg bw/day. Ref.: 87 3.3.8.2. Teratogenicity Teratogenicity study in the rabbit Guideline: OECD guideline no. 414 (adopted 22nd January 2001) Date of test : May-July 2001 Species/strain: Chinchilla rabbit Group size: 24 mated females Test substance: HR 00/600306 (Climbazole, purity min. 98%) Batch no.: 20072001 Dose levels: 0, 15, 30, 60 mg/kg bw/day Route: oral; gavage Exposure: days 6 through 27 of pregnancy GLP:","page":24,"pdf":"sccp_o_027.pdf","row_type":"noael_study","study_id":"sccp_o_027_noael_007"}
SCCS_vision_codex NOAEL =30 mg/kg bw/day rat oral - developmental toxicity {"citation":"Ref.: 17 Teratogenicity study in the rat (1) Guideline: teratogenicity study (1981) according to guidelines at the time Species/strain: BAY: FB30 rat Group size: 25 inseminated females T","dose":"the highest dose group.","effect":"the highest dose group. This difference in sex ratio was not considered to be test item-related. Examination of viscera, skeleton, and cartilage revealed no Climbazole-related foetal abnormalities. Conclusion No teratogenic effects were observed in this study with rabbits. Maternal toxicity (alopecia, reduced weight gain) was seen at 30 and 60 mg/kg bw/day. Embryotoxic effects (increased post- implantational losses) seen in the highest dose group are considered to be secondary to the effects on dams. The proposed NOAEL (embryotoxicity) is 30 mg/kg bw/day. Based on maternal toxicity at the two higher doses, 15 mg/kg bw/day is considered a NOAEL for maternal toxicity. Ref.: 17 Teratogenicity study in the rat (1) Guideline: teratogenicity study (1981) according to guidelines at the time Species/strain: BAY: FB30 rat Group size: 25 inseminated females Test substance: BAY e 6975 (Climbazole, purity not stated) Batch no.: 570327 Dose levels: 0, 10, 30, 100 mg/kg bw/day Route: oral; gavage Exposure: days 6 to 15 of pregnancy, inclusi","page":25,"pdf":"sccp_o_027.pdf","row_type":"noael_study","study_id":"sccp_o_027_noael_010"}
SCCS_vision_codex NOAEL =15 mg/kg bw/day rat oral 6 to day developmental toxicity {"citation":"Ref.: 17 Teratogenicity study in the rat (1) Guideline: teratogenicity study (1981) according to guidelines at the time Species/strain: BAY: FB30 rat Group size: 25 inseminated females T","dose":"Maternal toxicity (alopecia, reduced weight gain) was seen at 30 and 60 mg/kg bw/day.","effect":"on, and cartilage revealed no Climbazole-related foetal abnormalities. Conclusion No teratogenic effects were observed in this study with rabbits. Maternal toxicity (alopecia, reduced weight gain) was seen at 30 and 60 mg/kg bw/day. Embryotoxic effects (increased post- implantational losses) seen in the highest dose group are considered to be secondary to the effects on dams. The proposed NOAEL (embryotoxicity) is 30 mg/kg bw/day. Based on maternal toxicity at the two higher doses, 15 mg/kg bw/day is considered a NOAEL for maternal toxicity. Ref.: 17 Teratogenicity study in the rat (1) Guideline: teratogenicity study (1981) according to guidelines at the time Species/strain: BAY: FB30 rat Group size: 25 inseminated females Test substance: BAY e 6975 (Climbazole, purity not stated) Batch no.: 570327 Dose levels: 0, 10, 30, 100 mg/kg bw/day Route: oral; gavage Exposure: days 6 to 15 of pregnancy, inclusive GLP: no information (test performed in 1981, prior to GLP regulations) Climbazole was administered daily from day 6 to day","page":25,"pdf":"sccp_o_027.pdf","row_type":"noael_study","study_id":"sccp_o_027_noael_011"}
SCCS_vision_codex NOAEL =10 mg/kg rat - - developmental toxicity {"citation":"Ref.: 16 Teratogenicity study in the rat (2) Guideline: teratogenicity study (1979) according to guidelines at the time Species/strain: Charles River CD® rat Group size: 25 inseminated f","dose":"The laboratory concludes that no signs of teratogenic effects were seen in this teratogenicity study with rats with applied doses of 10 to 100 mg/kg during gestation days 6 through 15.","effect":"ticular study appear to be reliable. Conclusion The study was neither conducted in full compliance with the respective current OECD Guideline, nor has formal adherence to GLP principles been documented and reported. This makes the results difficult to interpret, especially in the case of such a specialised area as teratogenicity. The laboratory concludes that no signs of teratogenic effects were seen in this teratogenicity study with rats with applied doses of 10 to 100 mg/kg during gestation days 6 through 15. A NOAEL of 10 mg/kg has been identified for maternal toxicity. Embryotoxic effects were observed at 100 mg/kg and were judged to be secondary effects to the maternal toxicity. Ref.: 16 Teratogenicity study in the rat (2) Guideline: teratogenicity study (1979) according to guidelines at the time Species/strain: Charles River CD® rat Group size: 25 inseminated females Test substance: Compound No. 34054 (Climbazole, purity not stated)","page":26,"pdf":"sccp_o_027.pdf","row_type":"noael_study","study_id":"sccp_o_027_noael_012"}
SCCS_vision_codex NOAEL =7.2 mg/kg rat - - developmental toxicity {"citation":"Ref.: 85 Additional studies The dossier contains a teratogenicity study from 1977, in which only one dosage level (100 mg/kg bw/day) was tested","dose":"The authors conclude that skeletal variations have been observed in pups at maternal doses of 36 and 100 mg/kg bw/day.","effect":"velopmental toxicity study was neither conducted in full compliance with the respective current OECD Guideline, nor has formal adherence to GLP principles been documented and reported. The lack of the full raw data package makes the results difficult to interpret. The authors conclude that skeletal variations have been observed in pups at maternal doses of 36 and 100 mg/kg bw/day. Maternal toxicity was obvious at 36 and 100 mg/kg bw/day, 4 dams died at the highest dose. The lowest dose (7.2mg/kg) was found to be a NOAEL. There were no clear- cut indications of specific teratogenic effects at any dose level. Ref.: 85 Additional studies The dossier contains a teratogenicity study from 1977, in which only one dosage level (100 mg/kg bw/day) was tested. Viewing the restricted aim (dose-range finding study) and the age of the study, it is not discussed in detail. Ref.: 31 Finally, a so-called \"peri-/postnatal toxicity study\" is provided, in which 20 inseminated female rats were administered Compound N°34054 (Climbazole, purity not","page":28,"pdf":"sccp_o_027.pdf","row_type":"noael_study","study_id":"sccp_o_027_noael_013"}
SCCS_vision_codex NOAEL =5 mg/kg/day rat oral 90d developmental toxicity {"dose":"Nevertheless, based on the available information, a cautious NOEL-value of 5 mg/kg/day can be deduced from the 90d oral study with the rat.","effect":"te were measured in blood plasma and urine. Therefore, the absorption value for the calculation of the MoS for Climbazole will be considered 100% until sound dermal absorption data are provided. 9. With regard to long term toxicity studies : The dossier clearly suffers from the age of the studies. Nearly all of them have been performed between 1975 and 1983, before GLP-regulations were in place. The descriptions are brief and the raw data are incomplete. Nevertheless, based on the available information, a cautious NOEL-value of 5 mg/kg/day can be deduced from the 90d oral study with the rat. Chronic and carcinogenicity studies are not available. 10. With regard to the teratogenic effects of the substance, a relatively recent study (2001) provides a NOAEL (embryotoxicity) of 30 mg/kg bw/day and a NOAEL (maternal toxicity) of 15 mg/kg bw/day. 11. With regard to the mutagenicity/genotoxicity data The presented tests are old and have not been performed according to recent guidelines. They all show negative results. Due to the lack o","page":33,"pdf":"sccp_o_027.pdf","row_type":"noael_study","study_id":"sccp_o_027_noael_014"}
SCCS_vision_codex NOAEL =50 mg/kg bw/day rat oral sub-chronic repeated dose toxicity {"citation":"Ref.: 30 42-day oral toxicity study with the dog Guideline: 42-day oral toxicity test (1974) according to guidelines at the time Species/strain: Beagle dog Group size: 2 males + 2 female","dose":"The study is acceptable as a dose-finding (pilot) experiment.","effect":"SCCP/0918/05 Opinion on Climbazole (P64) 15 Conclusion The study was neither conducted in full compliance with the respective current OECD Guideline, nor has formal adherence to GLP principles been documented and reported. However, due to the availability of detailed information on the study design and findings (including some individual animal data), limited validity in terms of scientific criteria can be assigned. The study is acceptable as a dose-finding (pilot) experiment. Its results indicate that the NOAEL for Climbazole following repeated (sub-chronic) daily per oral dosing in the rat is lower than 50 mg/kg bw/day. The observed adverse effects were blood biochemical changes and morphological organ damage in the liver. Ref.: 30 42-day oral toxicity study with the dog Guideline: 42-day oral toxicity test (1974) according to guidelines at the time Species/strain: Beagle dog Group size: 2 males + 2 females Test substance: BAY e 6975 (Climbazole, purity not stated) Batch no.: 483751 Dose levels: 0, 100 mg/kg bw/day we","page":15,"pdf":"sccp_o_027.pdf","row_type":"noael_study","study_id":"sccp_o_027_noael_001"}
SCCS_vision_codex NOAEL =5 mg/kg bw/day rat oral 13 weeks NOAEL study {"citation":"Ref.: 2 90-day oral toxicity study with the dog Guideline: 90-day oral toxicity test (1980) according to guidelines at the time Species/strain: Beagle dog Group size: 3 males + 3 females","dose":"SCCP/0918/05 Opinion on Climbazole (P64) 17 Test substance-related effects were observed following daily p.o. dosing of rats over 13 weeks at the intermediate and high dose levels (15 and 45 mg/kg bw/day).","effect":"SCCP/0918/05 Opinion on Climbazole (P64) 17 Test substance-related effects were observed following daily p.o. dosing of rats over 13 weeks at the intermediate and high dose levels (15 and 45 mg/kg bw/day). The liver was identified as target organ for the effects of Climbazole. Because the effects on the liver at 15 mg/kg bw/day (increased liver weight without histopathological evidence of toxicity, P450 induction) were not judged to be clinical relevant, this dose is regarded as a NOAEL by the experimenters. Conclusion Viewing the absence of the full raw data package, it appears to be safer to use the NOEL value of 5 mg/kg bw/day for the calculation of the MoS of Climbazole. Ref.: 2 90-day oral toxicity study with the dog Guideline: 90-day oral toxicity test (1980) according to guidelines at the time Species/strain: Beagle dog Group size: 3 males + 3 females Test substance: BAY e 6975 (Climbazole, purity not stated) Batch no.: 483751 Dose levels: 0, 5, 10, 20 mg/kg bw/day Route: oral; capsule","page":17,"pdf":"sccp_o_027.pdf","row_type":"noael_study","study_id":"sccp_o_027_noael_003"}
SCCS_vision_codex NOAEL =20 mg/kg bw/day dog - sub-chronic repeated dose toxicity {"citation":"Ref.: 3 3","dose":"Based on the reported study results, the laboratory proposes to use the highest tested dose of 20 mg/kg bw/day as the NOAEL in this sub-chronic peroral toxicity study in dogs.","effect":"Conclusion The study was neither conducted in full compliance with the respective current OECD Guideline, nor has formal adherence to GLP principles been documented and reported. However, due to the availability of detailed information on the study design and findings (including some individual animal data), satisfactory validity in terms of scientific criteria can be assigned to this experiment. Based on the reported study results, the laboratory proposes to use the highest tested dose of 20 mg/kg bw/day as the NOAEL in this sub-chronic peroral toxicity study in dogs. The only test substance-related effects observed exclusively in the high dose group were not considered as adverse effects but rather as signs of adaptive changes indicating increased metabolic activity. Viewing the absence of the full raw data package, it appears to be safer to take into account the NOEL value of 10 mg/kg bw/day. Ref.: 3 3.3.5.3. Chronic (> 12 months) toxicity No chronic toxicity studies have been conducted with Climbazole. 3.3.6. Mutagenicit","page":18,"pdf":"sccp_o_027.pdf","row_type":"noael_study","study_id":"sccp_o_027_noael_005"}
SCCS_vision_codex NOAEL =10 mg/kg bw/day dog - sub-chronic repeated dose toxicity {"citation":"Ref.: 3 3","dose":"Based on the reported study results, the laboratory proposes to use the highest tested dose of 20 mg/kg bw/day as the NOAEL in this sub-chronic peroral toxicity study in dogs.","effect":"teria can be assigned to this experiment. Based on the reported study results, the laboratory proposes to use the highest tested dose of 20 mg/kg bw/day as the NOAEL in this sub-chronic peroral toxicity study in dogs. The only test substance-related effects observed exclusively in the high dose group were not considered as adverse effects but rather as signs of adaptive changes indicating increased metabolic activity. Viewing the absence of the full raw data package, it appears to be safer to take into account the NOEL value of 10 mg/kg bw/day. Ref.: 3 3.3.5.3. Chronic (> 12 months) toxicity No chronic toxicity studies have been conducted with Climbazole. 3.3.6. Mutagenicity / Genotoxicity 3.3.6.1. Mutagenicity / Genotoxicity in vitro Ames test 1 (parent compound) Guideline: Ames test (1977) according to guidelines at the time Species/strain: Salmonella typhimurium, TA100, TA1537, TA98 Replicates: 2 Test substance: BAY e 6975 (Climbazole, purity not stated) Batch no.: 323568 Concentrations: 0, 3.15, 10, 31.5, 100, 315, 100","page":18,"pdf":"sccp_o_027.pdf","row_type":"noael_study","study_id":"sccp_o_027_noael_006"}
SCCS_vision_codex NOAEL =7.2 mg/kg bw/day rat oral - NOAEL study {"citation":"Ref.: 87 3","dose":"At the 36 mg/kg bw/day treatment level, the female rats exhibited slight-to-moderate toxicity during the initial stages of treatment with no observable effects on estrous or stillbirths.","effect":"he initial stages of treatment which caused disruption of the estrous cycles and an increased number of stillbirths. At the 36 mg/kg bw/day treatment level, the female rats exhibited slight-to-moderate toxicity during the initial stages of treatment with no observable effects on estrous or stillbirths. Embryotoxicity observed at 36 and 100 mg/kg bw/day consisted in decreased numbers of life pups at birth and was judged to be a secondary effect to maternal toxicity. Viewing the lack of full raw data, the following NOAEL values are proposed: NOAEL (maternal toxicity) = 7.2 mg/kg bw/day, NOAEL (embryotoxicity) = 36 mg/kg bw/day. Ref.: 87 3.3.8.2. Teratogenicity Teratogenicity study in the rabbit Guideline: OECD guideline no. 414 (adopted 22nd January 2001) Date of test : May-July 2001 Species/strain: Chinchilla rabbit Group size: 24 mated females Test substance: HR 00/600306 (Climbazole, purity min. 98%) Batch no.: 20072001 Dose levels: 0, 15, 30, 60 mg/kg bw/day Route: oral; gavage Exposure: days 6 through 27 of pregnancy GLP:","page":24,"pdf":"sccp_o_027.pdf","row_type":"noael_study","study_id":"sccp_o_027_noael_007"}
SCCS_vision_codex NOAEL =30 mg/kg bw/day rat oral - developmental toxicity {"citation":"Ref.: 17 Teratogenicity study in the rat (1) Guideline: teratogenicity study (1981) according to guidelines at the time Species/strain: BAY: FB30 rat Group size: 25 inseminated females T","dose":"the highest dose group.","effect":"the highest dose group. This difference in sex ratio was not considered to be test item-related. Examination of viscera, skeleton, and cartilage revealed no Climbazole-related foetal abnormalities. Conclusion No teratogenic effects were observed in this study with rabbits. Maternal toxicity (alopecia, reduced weight gain) was seen at 30 and 60 mg/kg bw/day. Embryotoxic effects (increased post- implantational losses) seen in the highest dose group are considered to be secondary to the effects on dams. The proposed NOAEL (embryotoxicity) is 30 mg/kg bw/day. Based on maternal toxicity at the two higher doses, 15 mg/kg bw/day is considered a NOAEL for maternal toxicity. Ref.: 17 Teratogenicity study in the rat (1) Guideline: teratogenicity study (1981) according to guidelines at the time Species/strain: BAY: FB30 rat Group size: 25 inseminated females Test substance: BAY e 6975 (Climbazole, purity not stated) Batch no.: 570327 Dose levels: 0, 10, 30, 100 mg/kg bw/day Route: oral; gavage Exposure: days 6 to 15 of pregnancy, inclusi","page":25,"pdf":"sccp_o_027.pdf","row_type":"noael_study","study_id":"sccp_o_027_noael_010"}
SCCS_vision_codex NOAEL =15 mg/kg bw/day rat oral 6 to day developmental toxicity {"citation":"Ref.: 17 Teratogenicity study in the rat (1) Guideline: teratogenicity study (1981) according to guidelines at the time Species/strain: BAY: FB30 rat Group size: 25 inseminated females T","dose":"Maternal toxicity (alopecia, reduced weight gain) was seen at 30 and 60 mg/kg bw/day.","effect":"on, and cartilage revealed no Climbazole-related foetal abnormalities. Conclusion No teratogenic effects were observed in this study with rabbits. Maternal toxicity (alopecia, reduced weight gain) was seen at 30 and 60 mg/kg bw/day. Embryotoxic effects (increased post- implantational losses) seen in the highest dose group are considered to be secondary to the effects on dams. The proposed NOAEL (embryotoxicity) is 30 mg/kg bw/day. Based on maternal toxicity at the two higher doses, 15 mg/kg bw/day is considered a NOAEL for maternal toxicity. Ref.: 17 Teratogenicity study in the rat (1) Guideline: teratogenicity study (1981) according to guidelines at the time Species/strain: BAY: FB30 rat Group size: 25 inseminated females Test substance: BAY e 6975 (Climbazole, purity not stated) Batch no.: 570327 Dose levels: 0, 10, 30, 100 mg/kg bw/day Route: oral; gavage Exposure: days 6 to 15 of pregnancy, inclusive GLP: no information (test performed in 1981, prior to GLP regulations) Climbazole was administered daily from day 6 to day","page":25,"pdf":"sccp_o_027.pdf","row_type":"noael_study","study_id":"sccp_o_027_noael_011"}
SCCS_vision_codex NOAEL =10 mg/kg rat - - developmental toxicity {"citation":"Ref.: 16 Teratogenicity study in the rat (2) Guideline: teratogenicity study (1979) according to guidelines at the time Species/strain: Charles River CD® rat Group size: 25 inseminated f","dose":"The laboratory concludes that no signs of teratogenic effects were seen in this teratogenicity study with rats with applied doses of 10 to 100 mg/kg during gestation days 6 through 15.","effect":"ticular study appear to be reliable. Conclusion The study was neither conducted in full compliance with the respective current OECD Guideline, nor has formal adherence to GLP principles been documented and reported. This makes the results difficult to interpret, especially in the case of such a specialised area as teratogenicity. The laboratory concludes that no signs of teratogenic effects were seen in this teratogenicity study with rats with applied doses of 10 to 100 mg/kg during gestation days 6 through 15. A NOAEL of 10 mg/kg has been identified for maternal toxicity. Embryotoxic effects were observed at 100 mg/kg and were judged to be secondary effects to the maternal toxicity. Ref.: 16 Teratogenicity study in the rat (2) Guideline: teratogenicity study (1979) according to guidelines at the time Species/strain: Charles River CD® rat Group size: 25 inseminated females Test substance: Compound No. 34054 (Climbazole, purity not stated)","page":26,"pdf":"sccp_o_027.pdf","row_type":"noael_study","study_id":"sccp_o_027_noael_012"}
SCCS_vision_codex NOAEL =7.2 mg/kg rat - - developmental toxicity {"citation":"Ref.: 85 Additional studies The dossier contains a teratogenicity study from 1977, in which only one dosage level (100 mg/kg bw/day) was tested","dose":"The authors conclude that skeletal variations have been observed in pups at maternal doses of 36 and 100 mg/kg bw/day.","effect":"velopmental toxicity study was neither conducted in full compliance with the respective current OECD Guideline, nor has formal adherence to GLP principles been documented and reported. The lack of the full raw data package makes the results difficult to interpret. The authors conclude that skeletal variations have been observed in pups at maternal doses of 36 and 100 mg/kg bw/day. Maternal toxicity was obvious at 36 and 100 mg/kg bw/day, 4 dams died at the highest dose. The lowest dose (7.2mg/kg) was found to be a NOAEL. There were no clear- cut indications of specific teratogenic effects at any dose level. Ref.: 85 Additional studies The dossier contains a teratogenicity study from 1977, in which only one dosage level (100 mg/kg bw/day) was tested. Viewing the restricted aim (dose-range finding study) and the age of the study, it is not discussed in detail. Ref.: 31 Finally, a so-called \"peri-/postnatal toxicity study\" is provided, in which 20 inseminated female rats were administered Compound N°34054 (Climbazole, purity not","page":28,"pdf":"sccp_o_027.pdf","row_type":"noael_study","study_id":"sccp_o_027_noael_013"}
SCCS_vision_codex NOAEL =5 mg/kg/day rat oral 90d developmental toxicity {"dose":"Nevertheless, based on the available information, a cautious NOEL-value of 5 mg/kg/day can be deduced from the 90d oral study with the rat.","effect":"te were measured in blood plasma and urine. Therefore, the absorption value for the calculation of the MoS for Climbazole will be considered 100% until sound dermal absorption data are provided. 9. With regard to long term toxicity studies : The dossier clearly suffers from the age of the studies. Nearly all of them have been performed between 1975 and 1983, before GLP-regulations were in place. The descriptions are brief and the raw data are incomplete. Nevertheless, based on the available information, a cautious NOEL-value of 5 mg/kg/day can be deduced from the 90d oral study with the rat. Chronic and carcinogenicity studies are not available. 10. With regard to the teratogenic effects of the substance, a relatively recent study (2001) provides a NOAEL (embryotoxicity) of 30 mg/kg bw/day and a NOAEL (maternal toxicity) of 15 mg/kg bw/day. 11. With regard to the mutagenicity/genotoxicity data The presented tests are old and have not been performed according to recent guidelines. They all show negative results. Due to the lack o","page":33,"pdf":"sccp_o_027.pdf","row_type":"noael_study","study_id":"sccp_o_027_noael_014"}
SCCS_vision_codex NOAEL =50 mg/kg bw/day rat oral sub-chronic repeated dose toxicity {"citation":"Ref.: 30 42-day oral toxicity study with the dog Guideline: 42-day oral toxicity test (1974) according to guidelines at the time Species/strain: Beagle dog Group size: 2 males + 2 female","dose":"The study is acceptable as a dose-finding (pilot) experiment.","effect":"SCCP/0918/05 Opinion on Climbazole (P64) 15 Conclusion The study was neither conducted in full compliance with the respective current OECD Guideline, nor has formal adherence to GLP principles been documented and reported. However, due to the availability of detailed information on the study design and findings (including some individual animal data), limited validity in terms of scientific criteria can be assigned. The study is acceptable as a dose-finding (pilot) experiment. Its results indicate that the NOAEL for Climbazole following repeated (sub-chronic) daily per oral dosing in the rat is lower than 50 mg/kg bw/day. The observed adverse effects were blood biochemical changes and morphological organ damage in the liver. Ref.: 30 42-day oral toxicity study with the dog Guideline: 42-day oral toxicity test (1974) according to guidelines at the time Species/strain: Beagle dog Group size: 2 males + 2 females Test substance: BAY e 6975 (Climbazole, purity not stated) Batch no.: 483751 Dose levels: 0, 100 mg/kg bw/day we","page":15,"pdf":"sccp_o_027.pdf","row_type":"noael_study","study_id":"sccp_o_027_noael_001"}
SCCS_vision_codex NOAEL =5 mg/kg bw/day rat oral 13 weeks NOAEL study {"citation":"Ref.: 2 90-day oral toxicity study with the dog Guideline: 90-day oral toxicity test (1980) according to guidelines at the time Species/strain: Beagle dog Group size: 3 males + 3 females","dose":"SCCP/0918/05 Opinion on Climbazole (P64) 17 Test substance-related effects were observed following daily p.o. dosing of rats over 13 weeks at the intermediate and high dose levels (15 and 45 mg/kg bw/day).","effect":"SCCP/0918/05 Opinion on Climbazole (P64) 17 Test substance-related effects were observed following daily p.o. dosing of rats over 13 weeks at the intermediate and high dose levels (15 and 45 mg/kg bw/day). The liver was identified as target organ for the effects of Climbazole. Because the effects on the liver at 15 mg/kg bw/day (increased liver weight without histopathological evidence of toxicity, P450 induction) were not judged to be clinical relevant, this dose is regarded as a NOAEL by the experimenters. Conclusion Viewing the absence of the full raw data package, it appears to be safer to use the NOEL value of 5 mg/kg bw/day for the calculation of the MoS of Climbazole. Ref.: 2 90-day oral toxicity study with the dog Guideline: 90-day oral toxicity test (1980) according to guidelines at the time Species/strain: Beagle dog Group size: 3 males + 3 females Test substance: BAY e 6975 (Climbazole, purity not stated) Batch no.: 483751 Dose levels: 0, 5, 10, 20 mg/kg bw/day Route: oral; capsule","page":17,"pdf":"sccp_o_027.pdf","row_type":"noael_study","study_id":"sccp_o_027_noael_003"}
SCCS_vision_codex NOAEL =20 mg/kg bw/day dog - sub-chronic repeated dose toxicity {"citation":"Ref.: 3 3","dose":"Based on the reported study results, the laboratory proposes to use the highest tested dose of 20 mg/kg bw/day as the NOAEL in this sub-chronic peroral toxicity study in dogs.","effect":"Conclusion The study was neither conducted in full compliance with the respective current OECD Guideline, nor has formal adherence to GLP principles been documented and reported. However, due to the availability of detailed information on the study design and findings (including some individual animal data), satisfactory validity in terms of scientific criteria can be assigned to this experiment. Based on the reported study results, the laboratory proposes to use the highest tested dose of 20 mg/kg bw/day as the NOAEL in this sub-chronic peroral toxicity study in dogs. The only test substance-related effects observed exclusively in the high dose group were not considered as adverse effects but rather as signs of adaptive changes indicating increased metabolic activity. Viewing the absence of the full raw data package, it appears to be safer to take into account the NOEL value of 10 mg/kg bw/day. Ref.: 3 3.3.5.3. Chronic (> 12 months) toxicity No chronic toxicity studies have been conducted with Climbazole. 3.3.6. Mutagenicit","page":18,"pdf":"sccp_o_027.pdf","row_type":"noael_study","study_id":"sccp_o_027_noael_005"}
SCCS_vision_codex NOAEL =10 mg/kg bw/day dog - sub-chronic repeated dose toxicity {"citation":"Ref.: 3 3","dose":"Based on the reported study results, the laboratory proposes to use the highest tested dose of 20 mg/kg bw/day as the NOAEL in this sub-chronic peroral toxicity study in dogs.","effect":"teria can be assigned to this experiment. Based on the reported study results, the laboratory proposes to use the highest tested dose of 20 mg/kg bw/day as the NOAEL in this sub-chronic peroral toxicity study in dogs. The only test substance-related effects observed exclusively in the high dose group were not considered as adverse effects but rather as signs of adaptive changes indicating increased metabolic activity. Viewing the absence of the full raw data package, it appears to be safer to take into account the NOEL value of 10 mg/kg bw/day. Ref.: 3 3.3.5.3. Chronic (> 12 months) toxicity No chronic toxicity studies have been conducted with Climbazole. 3.3.6. Mutagenicity / Genotoxicity 3.3.6.1. Mutagenicity / Genotoxicity in vitro Ames test 1 (parent compound) Guideline: Ames test (1977) according to guidelines at the time Species/strain: Salmonella typhimurium, TA100, TA1537, TA98 Replicates: 2 Test substance: BAY e 6975 (Climbazole, purity not stated) Batch no.: 323568 Concentrations: 0, 3.15, 10, 31.5, 100, 315, 100","page":18,"pdf":"sccp_o_027.pdf","row_type":"noael_study","study_id":"sccp_o_027_noael_006"}
SCCS_vision_codex NOAEL =7.2 mg/kg bw/day rat oral - NOAEL study {"citation":"Ref.: 87 3","dose":"At the 36 mg/kg bw/day treatment level, the female rats exhibited slight-to-moderate toxicity during the initial stages of treatment with no observable effects on estrous or stillbirths.","effect":"he initial stages of treatment which caused disruption of the estrous cycles and an increased number of stillbirths. At the 36 mg/kg bw/day treatment level, the female rats exhibited slight-to-moderate toxicity during the initial stages of treatment with no observable effects on estrous or stillbirths. Embryotoxicity observed at 36 and 100 mg/kg bw/day consisted in decreased numbers of life pups at birth and was judged to be a secondary effect to maternal toxicity. Viewing the lack of full raw data, the following NOAEL values are proposed: NOAEL (maternal toxicity) = 7.2 mg/kg bw/day, NOAEL (embryotoxicity) = 36 mg/kg bw/day. Ref.: 87 3.3.8.2. Teratogenicity Teratogenicity study in the rabbit Guideline: OECD guideline no. 414 (adopted 22nd January 2001) Date of test : May-July 2001 Species/strain: Chinchilla rabbit Group size: 24 mated females Test substance: HR 00/600306 (Climbazole, purity min. 98%) Batch no.: 20072001 Dose levels: 0, 15, 30, 60 mg/kg bw/day Route: oral; gavage Exposure: days 6 through 27 of pregnancy GLP:","page":24,"pdf":"sccp_o_027.pdf","row_type":"noael_study","study_id":"sccp_o_027_noael_007"}
SCCS_vision_codex NOAEL =30 mg/kg bw/day rat oral - developmental toxicity {"citation":"Ref.: 17 Teratogenicity study in the rat (1) Guideline: teratogenicity study (1981) according to guidelines at the time Species/strain: BAY: FB30 rat Group size: 25 inseminated females T","dose":"the highest dose group.","effect":"the highest dose group. This difference in sex ratio was not considered to be test item-related. Examination of viscera, skeleton, and cartilage revealed no Climbazole-related foetal abnormalities. Conclusion No teratogenic effects were observed in this study with rabbits. Maternal toxicity (alopecia, reduced weight gain) was seen at 30 and 60 mg/kg bw/day. Embryotoxic effects (increased post- implantational losses) seen in the highest dose group are considered to be secondary to the effects on dams. The proposed NOAEL (embryotoxicity) is 30 mg/kg bw/day. Based on maternal toxicity at the two higher doses, 15 mg/kg bw/day is considered a NOAEL for maternal toxicity. Ref.: 17 Teratogenicity study in the rat (1) Guideline: teratogenicity study (1981) according to guidelines at the time Species/strain: BAY: FB30 rat Group size: 25 inseminated females Test substance: BAY e 6975 (Climbazole, purity not stated) Batch no.: 570327 Dose levels: 0, 10, 30, 100 mg/kg bw/day Route: oral; gavage Exposure: days 6 to 15 of pregnancy, inclusi","page":25,"pdf":"sccp_o_027.pdf","row_type":"noael_study","study_id":"sccp_o_027_noael_010"}
SCCS_vision_codex NOAEL =15 mg/kg bw/day rat oral 6 to day developmental toxicity {"citation":"Ref.: 17 Teratogenicity study in the rat (1) Guideline: teratogenicity study (1981) according to guidelines at the time Species/strain: BAY: FB30 rat Group size: 25 inseminated females T","dose":"Maternal toxicity (alopecia, reduced weight gain) was seen at 30 and 60 mg/kg bw/day.","effect":"on, and cartilage revealed no Climbazole-related foetal abnormalities. Conclusion No teratogenic effects were observed in this study with rabbits. Maternal toxicity (alopecia, reduced weight gain) was seen at 30 and 60 mg/kg bw/day. Embryotoxic effects (increased post- implantational losses) seen in the highest dose group are considered to be secondary to the effects on dams. The proposed NOAEL (embryotoxicity) is 30 mg/kg bw/day. Based on maternal toxicity at the two higher doses, 15 mg/kg bw/day is considered a NOAEL for maternal toxicity. Ref.: 17 Teratogenicity study in the rat (1) Guideline: teratogenicity study (1981) according to guidelines at the time Species/strain: BAY: FB30 rat Group size: 25 inseminated females Test substance: BAY e 6975 (Climbazole, purity not stated) Batch no.: 570327 Dose levels: 0, 10, 30, 100 mg/kg bw/day Route: oral; gavage Exposure: days 6 to 15 of pregnancy, inclusive GLP: no information (test performed in 1981, prior to GLP regulations) Climbazole was administered daily from day 6 to day","page":25,"pdf":"sccp_o_027.pdf","row_type":"noael_study","study_id":"sccp_o_027_noael_011"}
SCCS_vision_codex NOAEL =10 mg/kg rat - - developmental toxicity {"citation":"Ref.: 16 Teratogenicity study in the rat (2) Guideline: teratogenicity study (1979) according to guidelines at the time Species/strain: Charles River CD® rat Group size: 25 inseminated f","dose":"The laboratory concludes that no signs of teratogenic effects were seen in this teratogenicity study with rats with applied doses of 10 to 100 mg/kg during gestation days 6 through 15.","effect":"ticular study appear to be reliable. Conclusion The study was neither conducted in full compliance with the respective current OECD Guideline, nor has formal adherence to GLP principles been documented and reported. This makes the results difficult to interpret, especially in the case of such a specialised area as teratogenicity. The laboratory concludes that no signs of teratogenic effects were seen in this teratogenicity study with rats with applied doses of 10 to 100 mg/kg during gestation days 6 through 15. A NOAEL of 10 mg/kg has been identified for maternal toxicity. Embryotoxic effects were observed at 100 mg/kg and were judged to be secondary effects to the maternal toxicity. Ref.: 16 Teratogenicity study in the rat (2) Guideline: teratogenicity study (1979) according to guidelines at the time Species/strain: Charles River CD® rat Group size: 25 inseminated females Test substance: Compound No. 34054 (Climbazole, purity not stated)","page":26,"pdf":"sccp_o_027.pdf","row_type":"noael_study","study_id":"sccp_o_027_noael_012"}
SCCS_vision_codex NOAEL =7.2 mg/kg rat - - developmental toxicity {"citation":"Ref.: 85 Additional studies The dossier contains a teratogenicity study from 1977, in which only one dosage level (100 mg/kg bw/day) was tested","dose":"The authors conclude that skeletal variations have been observed in pups at maternal doses of 36 and 100 mg/kg bw/day.","effect":"velopmental toxicity study was neither conducted in full compliance with the respective current OECD Guideline, nor has formal adherence to GLP principles been documented and reported. The lack of the full raw data package makes the results difficult to interpret. The authors conclude that skeletal variations have been observed in pups at maternal doses of 36 and 100 mg/kg bw/day. Maternal toxicity was obvious at 36 and 100 mg/kg bw/day, 4 dams died at the highest dose. The lowest dose (7.2mg/kg) was found to be a NOAEL. There were no clear- cut indications of specific teratogenic effects at any dose level. Ref.: 85 Additional studies The dossier contains a teratogenicity study from 1977, in which only one dosage level (100 mg/kg bw/day) was tested. Viewing the restricted aim (dose-range finding study) and the age of the study, it is not discussed in detail. Ref.: 31 Finally, a so-called \"peri-/postnatal toxicity study\" is provided, in which 20 inseminated female rats were administered Compound N°34054 (Climbazole, purity not","page":28,"pdf":"sccp_o_027.pdf","row_type":"noael_study","study_id":"sccp_o_027_noael_013"}
SCCS_vision_codex NOAEL =5 mg/kg/day rat oral 90d developmental toxicity {"dose":"Nevertheless, based on the available information, a cautious NOEL-value of 5 mg/kg/day can be deduced from the 90d oral study with the rat.","effect":"te were measured in blood plasma and urine. Therefore, the absorption value for the calculation of the MoS for Climbazole will be considered 100% until sound dermal absorption data are provided. 9. With regard to long term toxicity studies : The dossier clearly suffers from the age of the studies. Nearly all of them have been performed between 1975 and 1983, before GLP-regulations were in place. The descriptions are brief and the raw data are incomplete. Nevertheless, based on the available information, a cautious NOEL-value of 5 mg/kg/day can be deduced from the 90d oral study with the rat. Chronic and carcinogenicity studies are not available. 10. With regard to the teratogenic effects of the substance, a relatively recent study (2001) provides a NOAEL (embryotoxicity) of 30 mg/kg bw/day and a NOAEL (maternal toxicity) of 15 mg/kg bw/day. 11. With regard to the mutagenicity/genotoxicity data The presented tests are old and have not been performed according to recent guidelines. They all show negative results. Due to the lack o","page":33,"pdf":"sccp_o_027.pdf","row_type":"noael_study","study_id":"sccp_o_027_noael_014"}
SCCS_vision_codex NOAEL =0.5 % rat oral 90 day dermal absorption {"dose":"se (SED) Ax0.001xSAS/60 = 0.026 mg/kg bw No observed effect level NOEL = 5 mg/kg bw/day (90 day, oral, rat) Margin of Safety NOEL / SED = 189 Calculation for the use of Climbazole at 0.5% in a cosmetic face cream Dermal absorption through human skin A (μg/cm2) = 1.25 µg/cm² Skin Area surface (1/2 head female) SAS (cm2) = 565 cm2 Typical body wei...","effect":"se (SED) Ax0.001xSAS/60 = 0.026 mg/kg bw No observed effect level NOEL = 5 mg/kg bw/day (90 day, oral, rat) Margin of Safety NOEL / SED = 189 Calculation for the use of Climbazole at 0.5% in a cosmetic face cream Dermal absorption through human skin A (μg/cm2) = 1.25 µg/cm² Skin Area surface (1/2 head female) SAS (cm2) = 565 cm2 Typical body weight of human = 60 kg Systemic exposure dose (SED) Ax0.001xSAS/60 = 0.012 mg/kg bw No observed effect level NOEL = 5 mg/kg bw/day (90 day, oral, rat) Margin of Safety NOEL / SED = 425 Calculation for the use of Climbazole at 0.5% in leave-on body lotion Dermal absorption through human skin A (μg/cm2) = 1.25 µg/cm² Skin Area surface (whole body) SAS (cm2) = 18,000 cm2 Typical body weight of human = 60 kg Systemic exposure dose (SED) Ax0.001xSAS/60 = 0.38 mg/kg bw No observed effect level NOEL = 5 mg/kg bw/day (90 day, oral, rat) Margin of Safety NOEL / SED = 13 3.3.14. Discussion Physico-chemical specifications The physico-chemical section has been updated and completed and","page":24,"pdf":"sccp_o_164.pdf","row_type":"noael_study","study_id":"sccp_o_164_noael_008"}
SCCS_vision_codex NOAEL =0.5 % rat oral 90 day dermal absorption {"dose":"se (SED) Ax0.001xSAS/60 = 0.026 mg/kg bw No observed effect level NOEL = 5 mg/kg bw/day (90 day, oral, rat) Margin of Safety NOEL / SED = 189 Calculation for the use of Climbazole at 0.5% in a cosmetic face cream Dermal absorption through human skin A (μg/cm2) = 1.25 µg/cm² Skin Area surface (1/2 head female) SAS (cm2) = 565 cm2 Typical body wei...","effect":"se (SED) Ax0.001xSAS/60 = 0.026 mg/kg bw No observed effect level NOEL = 5 mg/kg bw/day (90 day, oral, rat) Margin of Safety NOEL / SED = 189 Calculation for the use of Climbazole at 0.5% in a cosmetic face cream Dermal absorption through human skin A (μg/cm2) = 1.25 µg/cm² Skin Area surface (1/2 head female) SAS (cm2) = 565 cm2 Typical body weight of human = 60 kg Systemic exposure dose (SED) Ax0.001xSAS/60 = 0.012 mg/kg bw No observed effect level NOEL = 5 mg/kg bw/day (90 day, oral, rat) Margin of Safety NOEL / SED = 425 Calculation for the use of Climbazole at 0.5% in leave-on body lotion Dermal absorption through human skin A (μg/cm2) = 1.25 µg/cm² Skin Area surface (whole body) SAS (cm2) = 18,000 cm2 Typical body weight of human = 60 kg Systemic exposure dose (SED) Ax0.001xSAS/60 = 0.38 mg/kg bw No observed effect level NOEL = 5 mg/kg bw/day (90 day, oral, rat) Margin of Safety NOEL / SED = 13 3.3.14. Discussion Physico-chemical specifications The physico-chemical section has been updated and completed and","page":24,"pdf":"sccp_o_164.pdf","row_type":"noael_study","study_id":"sccp_o_164_noael_008"}
SCCS_vision_codex NOAEL =0.5 % rat oral 90 day dermal absorption {"dose":"se (SED) Ax0.001xSAS/60 = 0.026 mg/kg bw No observed effect level NOEL = 5 mg/kg bw/day (90 day, oral, rat) Margin of Safety NOEL / SED = 189 Calculation for the use of Climbazole at 0.5% in a cosmetic face cream Dermal absorption through human skin A (μg/cm2) = 1.25 µg/cm² Skin Area surface (1/2 head female) SAS (cm2) = 565 cm2 Typical body wei...","effect":"se (SED) Ax0.001xSAS/60 = 0.026 mg/kg bw No observed effect level NOEL = 5 mg/kg bw/day (90 day, oral, rat) Margin of Safety NOEL / SED = 189 Calculation for the use of Climbazole at 0.5% in a cosmetic face cream Dermal absorption through human skin A (μg/cm2) = 1.25 µg/cm² Skin Area surface (1/2 head female) SAS (cm2) = 565 cm2 Typical body weight of human = 60 kg Systemic exposure dose (SED) Ax0.001xSAS/60 = 0.012 mg/kg bw No observed effect level NOEL = 5 mg/kg bw/day (90 day, oral, rat) Margin of Safety NOEL / SED = 425 Calculation for the use of Climbazole at 0.5% in leave-on body lotion Dermal absorption through human skin A (μg/cm2) = 1.25 µg/cm² Skin Area surface (whole body) SAS (cm2) = 18,000 cm2 Typical body weight of human = 60 kg Systemic exposure dose (SED) Ax0.001xSAS/60 = 0.38 mg/kg bw No observed effect level NOEL = 5 mg/kg bw/day (90 day, oral, rat) Margin of Safety NOEL / SED = 13 3.3.14. Discussion Physico-chemical specifications The physico-chemical section has been updated and completed and","page":24,"pdf":"sccp_o_164.pdf","row_type":"noael_study","study_id":"sccp_o_164_noael_008"}
SCCS_vision_codex NOAEL =0.5 % rat oral 90 day dermal absorption {"dose":"se (SED) Ax0.001xSAS/60 = 0.026 mg/kg bw No observed effect level NOEL = 5 mg/kg bw/day (90 day, oral, rat) Margin of Safety NOEL / SED = 189 Calculation for the use of Climbazole at 0.5% in a cosmetic face cream Dermal absorption through human skin A (μg/cm2) = 1.25 µg/cm² Skin Area surface (1/2 head female) SAS (cm2) = 565 cm2 Typical body wei...","effect":"se (SED) Ax0.001xSAS/60 = 0.026 mg/kg bw No observed effect level NOEL = 5 mg/kg bw/day (90 day, oral, rat) Margin of Safety NOEL / SED = 189 Calculation for the use of Climbazole at 0.5% in a cosmetic face cream Dermal absorption through human skin A (μg/cm2) = 1.25 µg/cm² Skin Area surface (1/2 head female) SAS (cm2) = 565 cm2 Typical body weight of human = 60 kg Systemic exposure dose (SED) Ax0.001xSAS/60 = 0.012 mg/kg bw No observed effect level NOEL = 5 mg/kg bw/day (90 day, oral, rat) Margin of Safety NOEL / SED = 425 Calculation for the use of Climbazole at 0.5% in leave-on body lotion Dermal absorption through human skin A (μg/cm2) = 1.25 µg/cm² Skin Area surface (whole body) SAS (cm2) = 18,000 cm2 Typical body weight of human = 60 kg Systemic exposure dose (SED) Ax0.001xSAS/60 = 0.38 mg/kg bw No observed effect level NOEL = 5 mg/kg bw/day (90 day, oral, rat) Margin of Safety NOEL / SED = 13 3.3.14. Discussion Physico-chemical specifications The physico-chemical section has been updated and completed and","page":24,"pdf":"sccp_o_164.pdf","row_type":"noael_study","study_id":"sccp_o_164_noael_008"}
SCCS_vision_codex NOAEL =5 mg/kg bw/day rat oral subacute repeated dose toxicity {"dose":"For ethical reasons and after a thorough re-examination of the available information, the SCCP proposed to accept the use of a cautious NOEL-value of 5 mg/kg bw/day, deduced from the 90d oral study with the rat.","effect":"ission contained subacute oral studies with rats and dogs, a subacute dermal toxicity study with the rabbit and subchronic oral studies with rats and dogs. The main problem was that the dossier suffered from the age of the studies. Nearly all of them were performed between 1975 and 1983, before GLP-regulations were in place. The descriptions were brief and the raw data incomplete. For ethical reasons and after a thorough re-examination of the available information, the SCCP proposed to accept the use of a cautious NOEL-value of 5 mg/kg bw/day, deduced from the 90d oral study with the rat.","page":16,"pdf":"sccp_o_164.pdf","row_type":"noael_study","study_id":"sccp_o_164_noael_001"}
SCCS_vision_codex NOAEL =5 mg/kg bw/day rat oral subacute repeated dose toxicity {"dose":"For ethical reasons and after a thorough re-examination of the available information, the SCCP proposed to accept the use of a cautious NOEL-value of 5 mg/kg bw/day, deduced from the 90d oral study with the rat.","effect":"ission contained subacute oral studies with rats and dogs, a subacute dermal toxicity study with the rabbit and subchronic oral studies with rats and dogs. The main problem was that the dossier suffered from the age of the studies. Nearly all of them were performed between 1975 and 1983, before GLP-regulations were in place. The descriptions were brief and the raw data incomplete. For ethical reasons and after a thorough re-examination of the available information, the SCCP proposed to accept the use of a cautious NOEL-value of 5 mg/kg bw/day, deduced from the 90d oral study with the rat.","page":16,"pdf":"sccp_o_164.pdf","row_type":"noael_study","study_id":"sccp_o_164_noael_001"}
SCCS_vision_codex NOAEL =5 mg/kg bw/day rat oral subacute repeated dose toxicity {"dose":"For ethical reasons and after a thorough re-examination of the available information, the SCCP proposed to accept the use of a cautious NOEL-value of 5 mg/kg bw/day, deduced from the 90d oral study with the rat.","effect":"ission contained subacute oral studies with rats and dogs, a subacute dermal toxicity study with the rabbit and subchronic oral studies with rats and dogs. The main problem was that the dossier suffered from the age of the studies. Nearly all of them were performed between 1975 and 1983, before GLP-regulations were in place. The descriptions were brief and the raw data incomplete. For ethical reasons and after a thorough re-examination of the available information, the SCCP proposed to accept the use of a cautious NOEL-value of 5 mg/kg bw/day, deduced from the 90d oral study with the rat.","page":16,"pdf":"sccp_o_164.pdf","row_type":"noael_study","study_id":"sccp_o_164_noael_001"}
SCCS_vision_codex NOAEL =5 mg/kg bw/day rat oral subacute repeated dose toxicity {"dose":"For ethical reasons and after a thorough re-examination of the available information, the SCCP proposed to accept the use of a cautious NOEL-value of 5 mg/kg bw/day, deduced from the 90d oral study with the rat.","effect":"ission contained subacute oral studies with rats and dogs, a subacute dermal toxicity study with the rabbit and subchronic oral studies with rats and dogs. The main problem was that the dossier suffered from the age of the studies. Nearly all of them were performed between 1975 and 1983, before GLP-regulations were in place. The descriptions were brief and the raw data incomplete. For ethical reasons and after a thorough re-examination of the available information, the SCCP proposed to accept the use of a cautious NOEL-value of 5 mg/kg bw/day, deduced from the 90d oral study with the rat.","page":16,"pdf":"sccp_o_164.pdf","row_type":"noael_study","study_id":"sccp_o_164_noael_001"}
SCCS_vision_codex NOAEL =6 - - - - NOAEL study {"effect":"Unlabeled table on page 6: descriptions and raw data, the SCCP deduced a conservative NOEL value of","page":6,"pdf":"sccs_o_120.pdf","row_type":"noael_study","study_id":"sccs_o_120_noael_014"}
SCCS_vision_codex NOAEL =6 - - - - NOAEL study {"effect":"Unlabeled table on page 6: descriptions and raw data, the SCCP deduced a conservative NOEL value of","page":6,"pdf":"sccs_o_120.pdf","row_type":"noael_study","study_id":"sccs_o_120_noael_014"}
SCCS_vision_codex NOAEL =6 - - - - NOAEL study {"effect":"Unlabeled table on page 6: descriptions and raw data, the SCCP deduced a conservative NOEL value of","page":6,"pdf":"sccs_o_120.pdf","row_type":"noael_study","study_id":"sccs_o_120_noael_014"}
SCCS_vision_codex NOAEL =6 - - - - NOAEL study {"effect":"Unlabeled table on page 6: descriptions and raw data, the SCCP deduced a conservative NOEL value of","page":6,"pdf":"sccs_o_120.pdf","row_type":"noael_study","study_id":"sccs_o_120_noael_014"}
SCCS_vision_codex NOAEL =30 mg/kg bw/day rat - - reproductive toxicity {"citation":"Ref.: 50 3","dose":"ative control) in hepatocytes isolated from treated male rats.","effect":"ative control) in hepatocytes isolated from treated male rats. Therefore they conclude that Climbazole was found negative in the in vivo UDS test in rats, when tested up to the maximum tolerated dose level. Ref.: 50 3.3.7. Carcinogenicity No data submitted 3.3.8. Reproductive toxicity Taken from SCCP/0981/05: A 1-generation reproduction study was presented, though its relevance was questioned. With regard to the teratogenic effects of the substance, the SCCP opinion mentions a study of 2001 providing a useful NOAEL (embryotoxicity) of 30 mg/kg bw/day and a NOAEL (maternal toxicity) of 15 mg/kg bw/day. 3.3.9. Toxicokinetics Taken from SCCP/0981/05: In vivo metabolic disposition studies in humans, dogs, rats and mice were presented in the previous SCCP submission. They showed that Climbazole appeared to be rapidly metabolised into its major metabolite through first pass metabolism. Excretion mainly occurred through the bile. Again, the presented data package contained old tests, which reduced their scientific validity. The","page":22,"pdf":"sccp_o_164.pdf","row_type":"noael_study","study_id":"sccp_o_164_noael_002"}
SCCS_vision_codex NOAEL =30 mg/kg bw/day rat - - reproductive toxicity {"citation":"Ref.: 50 3","dose":"ative control) in hepatocytes isolated from treated male rats.","effect":"ative control) in hepatocytes isolated from treated male rats. Therefore they conclude that Climbazole was found negative in the in vivo UDS test in rats, when tested up to the maximum tolerated dose level. Ref.: 50 3.3.7. Carcinogenicity No data submitted 3.3.8. Reproductive toxicity Taken from SCCP/0981/05: A 1-generation reproduction study was presented, though its relevance was questioned. With regard to the teratogenic effects of the substance, the SCCP opinion mentions a study of 2001 providing a useful NOAEL (embryotoxicity) of 30 mg/kg bw/day and a NOAEL (maternal toxicity) of 15 mg/kg bw/day. 3.3.9. Toxicokinetics Taken from SCCP/0981/05: In vivo metabolic disposition studies in humans, dogs, rats and mice were presented in the previous SCCP submission. They showed that Climbazole appeared to be rapidly metabolised into its major metabolite through first pass metabolism. Excretion mainly occurred through the bile. Again, the presented data package contained old tests, which reduced their scientific validity. The","page":22,"pdf":"sccp_o_164.pdf","row_type":"noael_study","study_id":"sccp_o_164_noael_002"}
SCCS_vision_codex NOAEL =30 mg/kg bw/day rat - - reproductive toxicity {"citation":"Ref.: 50 3","dose":"ative control) in hepatocytes isolated from treated male rats.","effect":"ative control) in hepatocytes isolated from treated male rats. Therefore they conclude that Climbazole was found negative in the in vivo UDS test in rats, when tested up to the maximum tolerated dose level. Ref.: 50 3.3.7. Carcinogenicity No data submitted 3.3.8. Reproductive toxicity Taken from SCCP/0981/05: A 1-generation reproduction study was presented, though its relevance was questioned. With regard to the teratogenic effects of the substance, the SCCP opinion mentions a study of 2001 providing a useful NOAEL (embryotoxicity) of 30 mg/kg bw/day and a NOAEL (maternal toxicity) of 15 mg/kg bw/day. 3.3.9. Toxicokinetics Taken from SCCP/0981/05: In vivo metabolic disposition studies in humans, dogs, rats and mice were presented in the previous SCCP submission. They showed that Climbazole appeared to be rapidly metabolised into its major metabolite through first pass metabolism. Excretion mainly occurred through the bile. Again, the presented data package contained old tests, which reduced their scientific validity. The","page":22,"pdf":"sccp_o_164.pdf","row_type":"noael_study","study_id":"sccp_o_164_noael_002"}
SCCS_vision_codex NOAEL =30 mg/kg bw/day rat - - reproductive toxicity {"citation":"Ref.: 50 3","dose":"ative control) in hepatocytes isolated from treated male rats.","effect":"ative control) in hepatocytes isolated from treated male rats. Therefore they conclude that Climbazole was found negative in the in vivo UDS test in rats, when tested up to the maximum tolerated dose level. Ref.: 50 3.3.7. Carcinogenicity No data submitted 3.3.8. Reproductive toxicity Taken from SCCP/0981/05: A 1-generation reproduction study was presented, though its relevance was questioned. With regard to the teratogenic effects of the substance, the SCCP opinion mentions a study of 2001 providing a useful NOAEL (embryotoxicity) of 30 mg/kg bw/day and a NOAEL (maternal toxicity) of 15 mg/kg bw/day. 3.3.9. Toxicokinetics Taken from SCCP/0981/05: In vivo metabolic disposition studies in humans, dogs, rats and mice were presented in the previous SCCP submission. They showed that Climbazole appeared to be rapidly metabolised into its major metabolite through first pass metabolism. Excretion mainly occurred through the bile. Again, the presented data package contained old tests, which reduced their scientific validity. The","page":22,"pdf":"sccp_o_164.pdf","row_type":"noael_study","study_id":"sccp_o_164_noael_002"}
ToxValDB_ECHA_IUCLID 8 endpoints
Source Endpoint Type Value Unit Species Route Duration Study Type Reference
ToxValDB_ECHA_IUCLID LOAEC =69.1 mg/m3 Rat inhalation acute; 6 hours acute QUALITY=2 (reliable with restrictions); STORED_SOURCE_RECORD=https://clowder.edap-cluster.com/files/66059786e4b063812d6fa765; RECORD_SOURCE_LEVEL=Extraction document; SOURCE_URL=https://echa.europa.eu/; SUBSOURCE_URL=https://echa.europa.eu/registration-dossier/-/registered-dossier/11657/7/6/3?documentUUID=1364b88b-e4e8-47e3-8a26-48e63ddc73db; YEAR=1991; ORIGINAL_YEAR=1991; STUDY_GROUP=ECHA IUCLID:15827862: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_4721f23b153074afa43f0948de5cd354
ToxValDB_ECHA_IUCLID LOAEL =50 mg/kg bw/day Rat oral short-term; 4 weeks short-term QUALITY=2 (reliable with restrictions); STORED_SOURCE_RECORD=https://clowder.edap-cluster.com/files/669eae2ae4b0a7c65d1c7ec1; RECORD_SOURCE_LEVEL=Extraction document; SOURCE_URL=https://echa.europa.eu/; SUBSOURCE_URL=https://echa.europa.eu/registration-dossier/-/registered-dossier/11657/7/6/2?documentUUID=1364b88b-e4e8-47e3-8a26-48e63ddc73db; YEAR=1991; ORIGINAL_YEAR=1991; STUDY_GROUP=ECHA IUCLID:15842923:M:--; 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_1427ae6075de287658800b7d76cf6a11
ToxValDB_ECHA_IUCLID NOAEC =44.3 mg/m3 Rat inhalation acute; 6 hours acute QUALITY=2 (reliable with restrictions); STORED_SOURCE_RECORD=https://clowder.edap-cluster.com/files/66059786e4b063812d6fa765; RECORD_SOURCE_LEVEL=Extraction document; SOURCE_URL=https://echa.europa.eu/; SUBSOURCE_URL=https://echa.europa.eu/registration-dossier/-/registered-dossier/11657/7/6/3?documentUUID=1364b88b-e4e8-47e3-8a26-48e63ddc73db; YEAR=1991; ORIGINAL_YEAR=1991; STUDY_GROUP=ECHA IUCLID:15827704: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_e55c08276e86996f04d37d0825a6bc15
ToxValDB_ECHA_IUCLID NOAEL =60 mg/kg bw/day Rabbit oral - developmental QUALITY=1 (reliable without restriction); STORED_SOURCE_RECORD=https://clowder.edap-cluster.com/files/669eac26e4b0a7c65d1bd9be; RECORD_SOURCE_LEVEL=Extraction document; SOURCE_URL=https://echa.europa.eu/; SUBSOURCE_URL=https://echa.europa.eu/registration-dossier/-/registered-dossier/11657/7/9/3?documentUUID=1364b88b-e4e8-47e3-8a26-48e63ddc73db; YEAR=1991; ORIGINAL_YEAR=1991; STUDY_GROUP=ECHA IUCLID:15821188:M/F:-fetal; QC_CATEGORY=Programmatically extracted from structured data source; Source overall passed QC, but this record was not manually checked; QC_STATUS=not determined; SOURCE_HASH=ToxValhc_5781546d7f3227d812b9a6aa6ba29437
ToxValDB_ECHA_IUCLID NOAEL =45 mg/kg bw/day Rat oral subchronic; 3 months subchronic QUALITY=2 (reliable with restrictions); STORED_SOURCE_RECORD=https://clowder.edap-cluster.com/files/669eae2ae4b0a7c65d1c7eb3; RECORD_SOURCE_LEVEL=Extraction document; SOURCE_URL=https://echa.europa.eu/; SUBSOURCE_URL=https://echa.europa.eu/registration-dossier/-/registered-dossier/11657/7/6/2?documentUUID=1364b88b-e4e8-47e3-8a26-48e63ddc73db; YEAR=1991; ORIGINAL_YEAR=1991; STUDY_GROUP=ECHA IUCLID:15836378: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_be01220da753b989fc72e3ce6552a088
ToxValDB_ECHA_IUCLID NOAEL =100 mg/kg bw/day Rat oral - reproduction developmental QUALITY=2 (reliable with restrictions); STORED_SOURCE_RECORD=https://clowder.edap-cluster.com/files/669eaaeee4b0a7c65d1b828e; RECORD_SOURCE_LEVEL=Extraction document; SOURCE_URL=https://echa.europa.eu/; SUBSOURCE_URL=https://echa.europa.eu/registration-dossier/-/registered-dossier/11657/7/9/2?documentUUID=1364b88b-e4e8-47e3-8a26-48e63ddc73db; YEAR=1991; ORIGINAL_YEAR=1991; STUDY_GROUP=ECHA IUCLID:15854975:M:P0-; 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_9db21f799146bcf44b75e04c78bfc029
ToxValDB_ECHA_IUCLID NOAEL =36 mg/kg bw/day Rat oral - reproduction developmental QUALITY=2 (reliable with restrictions); STORED_SOURCE_RECORD=https://clowder.edap-cluster.com/files/669eaaeee4b0a7c65d1b828e; RECORD_SOURCE_LEVEL=Extraction document; SOURCE_URL=https://echa.europa.eu/; SUBSOURCE_URL=https://echa.europa.eu/registration-dossier/-/registered-dossier/11657/7/9/2?documentUUID=1364b88b-e4e8-47e3-8a26-48e63ddc73db; YEAR=1991; ORIGINAL_YEAR=1991; TOXICOLOGICAL_EFFECT=P0: clinical signs; TOXICOLOGICAL_EFFECT_CATEGORY=clinical signs; STUDY_GROUP=ECHA IUCLID:15855884:F:P0-; 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_0a40477248a3e1827c455861a1846184
ToxValDB_ECHA_IUCLID NOEL =15 mg/kg bw/day Rabbit oral - reproduction developmental QUALITY=1 (reliable without restriction); STORED_SOURCE_RECORD=https://clowder.edap-cluster.com/files/669eac26e4b0a7c65d1bd9be; RECORD_SOURCE_LEVEL=Extraction document; SOURCE_URL=https://echa.europa.eu/; SUBSOURCE_URL=https://echa.europa.eu/registration-dossier/-/registered-dossier/11657/7/9/3?documentUUID=1364b88b-e4e8-47e3-8a26-48e63ddc73db; YEAR=1991; ORIGINAL_YEAR=1991; STUDY_GROUP=ECHA IUCLID:15822508: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_8b36956240bee1babfaa1d0b0026eb4d
ToxValDB_GESTIS_DNEL 1 endpoint
Source Endpoint Type Value Unit Species Route Duration Study Type Reference
ToxValDB_GESTIS_DNEL DNEL systemic =0.3 mg/m3 Human inhalation - Toxicity Value STORED_SOURCE_RECORD=https://clowder.edap-cluster.com/files/6543dd69e4b045b9ff7cd87e; RECORD_SOURCE_LEVEL=Extraction document; SOURCE_URL=https://www.dguv.de/ifa/gestis/gestis-dnel-liste/index-2.jsp; STUDY_GROUP=GESTIS DNEL:15630676:-:--; 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_0413edf15d15990d6f532335525b1156
UnifiedCodex:SCCS_SHADOW:beta.noael_studies 45 endpoints
Source Endpoint Type Value Unit Species Route Duration Study Type Reference
UnifiedCodex:SCCS_SHADOW:beta.noael_studies - 5 mg/kg bw/day rat oral 13 weeks - SOURCE_SUBDIR=sccp_o_027; REPORT_TITLE=Opinion on Climbazole COLIPA n° P64; OPINION_NUMBER=SCCP/0918/05; COMMITTEE=SCCP; REPORT_DATE=20 September 2005; VALUE_TEXT=5; DOSE=SCCP/0918/05 Opinion on Climbazole (P64) 17 Test substance-related effects were observed following daily p.o. dosing of rats over 13 weeks at the intermediate and high dose levels (15 and 45 mg/kg bw/day).; EFFECT=SCCP/0918/05 Opinion on Climbazole (P64) 17 Test substance-related effects were observed following daily p.o. dosing of rats over 13 weeks at the intermediate and high dose levels (15 and 45 mg/kg bw/day). The liver was identified as target organ for the effects of Climbazole. Because the effects on the liver at 15 mg/kg bw/day (increased liver weight without histopathological evidence of toxicity, P450 induction) were not judged to be clinical relevant, this dose is regarded as a NOAEL by the experimenters. Conclusion Viewing the absence of the full raw data package, it appears to be safer to use the NOEL value of 5 mg/kg bw/day for the calculation of the MoS of Climbazole. Ref.: 2 90-day oral toxicity study with the dog Guideline: 90-day oral toxicity test (1980) according to guidelines at the time Species/strain: Beagle dog Group size: 3 males + 3 females Test substance: BAY e 6975 (Climbazole, purity not stated) Batch no.: 483751 Dose levels: 0, 5, 10, 20 mg/kg bw/day Route: oral; capsule; CITATION=Ref.: 2 90-day oral toxicity study with the dog Guideline: 90-day oral toxicity test (1980) according to guidelines at the time Species/strain: Beagle dog Group size: 3 males + 3 females; CITATION_NUMBERS=[2,90,1980,3]; REFERENCE=Ref.: 2 90-day oral toxicity study with the dog Guideline: 90-day oral toxicity test (1980) according to guidelines at the time Species/strain: Beagle dog Group size: 3 males + 3 females; DETAILS_JSON={"cas_number":"38083-17-9","citation":"Ref.: 2 90-day oral toxicity study with the dog Guideline: 90-day oral toxicity test (1980) according to guidelines at the time Species/strain: Beagle dog Group size: 3 males + 3 females","dose":"SCCP/0918/05 Opinion on Climbazole (P64) 17 Test substance-related effects were observed following daily p.o. dosing of rats over 13 weeks at the intermediate and high dose levels (15 and 45 mg/kg bw/day).","duration":"13 weeks","effect":"SCCP/0918/05 Opinion on Climbazole (P64) 17 Test substance-related effects were observed following daily p.o. dosing of rats over 13 weeks at the intermediate and high dose levels (15 and 45 mg/kg bw/day). The liver was identified as target organ for the effects of Climbazole. Because the effects on the liver at 15 mg/kg bw/day (increased liver weight without histopathological evidence of toxicity, P450 induction) were not judged to be clinical relevant, this dose is regarded as a NOAEL by the experimenters. Conclusion Viewing the absence of the full raw data package, it appears to be safer to use the NOEL value of 5 mg/kg bw/day for the calculation of the MoS of Climbazole. Ref.: 2 90-day oral toxicity study with the dog Guideline: 90-day oral toxicity test (1980) according to guidelines at the time Species/strain: Beagle dog Group size: 3 males + 3 females Test substance: BAY e 6975 (Climbazole, purity not stated) Batch no.: 483751 Dose levels: 0, 5, 10, 20 mg/kg bw/day Route: oral; capsule","endpoint":"","ingredient":"Climbazole","loael_value":"","noael_unit":"mg/kg bw/day","noael_value":"5","page":17,"route":"oral","species":"rat","study_id":"sccp_o_027_noael_003"}
UnifiedCodex:SCCS_SHADOW:beta.noael_studies - 5 mg/kg bw/day rat oral 13 weeks - SOURCE_SUBDIR=sccp_o_027; REPORT_TITLE=Opinion on Climbazole COLIPA n° P64; OPINION_NUMBER=SCCP/0918/05; COMMITTEE=SCCP; REPORT_DATE=20 September 2005; VALUE_TEXT=5; DOSE=ollowing daily p.o. dosing of rats over 13 weeks at the intermediate and high dose levels (15 and 45 mg/kg bw/day).; EFFECT=ollowing daily p.o. dosing of rats over 13 weeks at the intermediate and high dose levels (15 and 45 mg/kg bw/day). The liver was identified as target organ for the effects of Climbazole. Because the effects on the liver at 15 mg/kg bw/day (increased liver weight without histopathological evidence of toxicity, P450 induction) were not judged to be clinical relevant, this dose is regarded as a NOAEL by the experimenters. Conclusion Viewing the absence of the full raw data package, it appears to be safer to use the NOEL value of 5 mg/kg bw/day for the calculation of the MoS of Climbazole. Ref.: 2 90-day oral toxicity study with the dog Guideline: 90-day oral toxicity test (1980) according to guidelines at the time Species/strain: Beagle dog Group size: 3 males + 3 females Test substance: BAY e 6975 (Climbazole, purity not stated) Batch no.: 483751 Dose levels: 0, 5, 10, 20 mg/kg bw/day Route: oral; capsules Exposure: 13 weeks, 7 days/week GLP: no information (test performed in 1980, prior to GLP regulations) Climbazole (BAY e; CITATION=Ref.: 2 90-day oral toxicity study with the dog Guideline: 90-day oral toxicity test (1980) according to guidelines at the time Species/strain: Beagle dog Group size: 3 males + 3 females; CITATION_NUMBERS=[2,90,1980,3]; REFERENCE=Ref.: 2 90-day oral toxicity study with the dog Guideline: 90-day oral toxicity test (1980) according to guidelines at the time Species/strain: Beagle dog Group size: 3 males + 3 females; DETAILS_JSON={"cas_number":"38083-17-9","citation":"Ref.: 2 90-day oral toxicity study with the dog Guideline: 90-day oral toxicity test (1980) according to guidelines at the time Species/strain: Beagle dog Group size: 3 males + 3 females","dose":"ollowing daily p.o. dosing of rats over 13 weeks at the intermediate and high dose levels (15 and 45 mg/kg bw/day).","duration":"13 weeks","effect":"ollowing daily p.o. dosing of rats over 13 weeks at the intermediate and high dose levels (15 and 45 mg/kg bw/day). The liver was identified as target organ for the effects of Climbazole. Because the effects on the liver at 15 mg/kg bw/day (increased liver weight without histopathological evidence of toxicity, P450 induction) were not judged to be clinical relevant, this dose is regarded as a NOAEL by the experimenters. Conclusion Viewing the absence of the full raw data package, it appears to be safer to use the NOEL value of 5 mg/kg bw/day for the calculation of the MoS of Climbazole. Ref.: 2 90-day oral toxicity study with the dog Guideline: 90-day oral toxicity test (1980) according to guidelines at the time Species/strain: Beagle dog Group size: 3 males + 3 females Test substance: BAY e 6975 (Climbazole, purity not stated) Batch no.: 483751 Dose levels: 0, 5, 10, 20 mg/kg bw/day Route: oral; capsules Exposure: 13 weeks, 7 days/week GLP: no information (test performed in 1980, prior to GLP regulations) Climbazole (BAY e","endpoint":"","ingredient":"Climbazole","loael_value":"","noael_unit":"mg/kg bw/day","noael_value":"5","page":17,"route":"oral","species":"rat","study_id":"sccp_o_027_noael_004"}
UnifiedCodex:SCCS_SHADOW:beta.noael_studies - =7.2 mg/kg bw/day rat oral - - SOURCE_SUBDIR=sccp_o_027; REPORT_TITLE=Opinion on Climbazole COLIPA n° P64; OPINION_NUMBER=SCCP/0918/05; COMMITTEE=SCCP; REPORT_DATE=20 September 2005; VALUE_TEXT== 7.2; DOSE=At the 36 mg/kg bw/day treatment level, the female rats exhibited slight-to-moderate toxicity during the initial stages of treatment with no observable effects on estrous or stillbirths.; EFFECT=he initial stages of treatment which caused disruption of the estrous cycles and an increased number of stillbirths. At the 36 mg/kg bw/day treatment level, the female rats exhibited slight-to-moderate toxicity during the initial stages of treatment with no observable effects on estrous or stillbirths. Embryotoxicity observed at 36 and 100 mg/kg bw/day consisted in decreased numbers of life pups at birth and was judged to be a secondary effect to maternal toxicity. Viewing the lack of full raw data, the following NOAEL values are proposed: NOAEL (maternal toxicity) = 7.2 mg/kg bw/day, NOAEL (embryotoxicity) = 36 mg/kg bw/day. Ref.: 87 3.3.8.2. Teratogenicity Teratogenicity study in the rabbit Guideline: OECD guideline no. 414 (adopted 22nd January 2001) Date of test : May-July 2001 Species/strain: Chinchilla rabbit Group size: 24 mated females Test substance: HR 00/600306 (Climbazole, purity min. 98%) Batch no.: 20072001 Dose levels: 0, 15, 30, 60 mg/kg bw/day Route: oral; gavage Exposure: days 6 through 27 of pregnancy GLP:; CITATION=Ref.: 87 3; CITATION_NUMBERS=[87,3]; REFERENCE=Ref.: 87 3; DETAILS_JSON={"cas_number":"38083-17-9","citation":"Ref.: 87 3","dose":"At the 36 mg/kg bw/day treatment level, the female rats exhibited slight-to-moderate toxicity during the initial stages of treatment with no observable effects on estrous or stillbirths.","duration":"","effect":"he initial stages of treatment which caused disruption of the estrous cycles and an increased number of stillbirths. At the 36 mg/kg bw/day treatment level, the female rats exhibited slight-to-moderate toxicity during the initial stages of treatment with no observable effects on estrous or stillbirths. Embryotoxicity observed at 36 and 100 mg/kg bw/day consisted in decreased numbers of life pups at birth and was judged to be a secondary effect to maternal toxicity. Viewing the lack of full raw data, the following NOAEL values are proposed: NOAEL (maternal toxicity) = 7.2 mg/kg bw/day, NOAEL (embryotoxicity) = 36 mg/kg bw/day. Ref.: 87 3.3.8.2. Teratogenicity Teratogenicity study in the rabbit Guideline: OECD guideline no. 414 (adopted 22nd January 2001) Date of test : May-July 2001 Species/strain: Chinchilla rabbit Group size: 24 mated females Test substance: HR 00/600306 (Climbazole, purity min. 98%) Batch no.: 20072001 Dose levels: 0, 15, 30, 60 mg/kg bw/day Route: oral; gavage Exposure: days 6 through 27 of pregnancy GLP:","endpoint":"","ingredient":"Climbazole","loael_value":"","noael_unit":"mg/kg bw/day","noael_value":"= 7.2","page":24,"route":"oral","species":"rat","study_id":"sccp_o_027_noael_007"}
UnifiedCodex:SCCS_SHADOW:beta.noael_studies - =7.2 mg/kg bw/day rat oral - - SOURCE_SUBDIR=sccp_o_027; REPORT_TITLE=Opinion on Climbazole COLIPA n° P64; OPINION_NUMBER=SCCP/0918/05; COMMITTEE=SCCP; REPORT_DATE=20 September 2005; VALUE_TEXT== 7.2; DOSE=At the 36 mg/kg bw/day treatment level, the female rats exhibited slight-to-moderate toxicity during the initial stages of treatment with no observable effects on estrous or stillbirths.; EFFECT=nt which caused disruption of the estrous cycles and an increased number of stillbirths. At the 36 mg/kg bw/day treatment level, the female rats exhibited slight-to-moderate toxicity during the initial stages of treatment with no observable effects on estrous or stillbirths. Embryotoxicity observed at 36 and 100 mg/kg bw/day consisted in decreased numbers of life pups at birth and was judged to be a secondary effect to maternal toxicity. Viewing the lack of full raw data, the following NOAEL values are proposed: NOAEL (maternal toxicity) = 7.2 mg/kg bw/day, NOAEL (embryotoxicity) = 36 mg/kg bw/day. Ref.: 87 3.3.8.2. Teratogenicity Teratogenicity study in the rabbit Guideline: OECD guideline no. 414 (adopted 22nd January 2001) Date of test : May-July 2001 Species/strain: Chinchilla rabbit Group size: 24 mated females Test substance: HR 00/600306 (Climbazole, purity min. 98%) Batch no.: 20072001 Dose levels: 0, 15, 30, 60 mg/kg bw/day Route: oral; gavage Exposure: days 6 through 27 of pregnancy GLP: in compliance Climbazole (; CITATION=Ref.: 87 3; CITATION_NUMBERS=[87,3]; REFERENCE=Ref.: 87 3; DETAILS_JSON={"cas_number":"38083-17-9","citation":"Ref.: 87 3","dose":"At the 36 mg/kg bw/day treatment level, the female rats exhibited slight-to-moderate toxicity during the initial stages of treatment with no observable effects on estrous or stillbirths.","duration":"","effect":"nt which caused disruption of the estrous cycles and an increased number of stillbirths. At the 36 mg/kg bw/day treatment level, the female rats exhibited slight-to-moderate toxicity during the initial stages of treatment with no observable effects on estrous or stillbirths. Embryotoxicity observed at 36 and 100 mg/kg bw/day consisted in decreased numbers of life pups at birth and was judged to be a secondary effect to maternal toxicity. Viewing the lack of full raw data, the following NOAEL values are proposed: NOAEL (maternal toxicity) = 7.2 mg/kg bw/day, NOAEL (embryotoxicity) = 36 mg/kg bw/day. Ref.: 87 3.3.8.2. Teratogenicity Teratogenicity study in the rabbit Guideline: OECD guideline no. 414 (adopted 22nd January 2001) Date of test : May-July 2001 Species/strain: Chinchilla rabbit Group size: 24 mated females Test substance: HR 00/600306 (Climbazole, purity min. 98%) Batch no.: 20072001 Dose levels: 0, 15, 30, 60 mg/kg bw/day Route: oral; gavage Exposure: days 6 through 27 of pregnancy GLP: in compliance Climbazole (","endpoint":"","ingredient":"Climbazole","loael_value":"","noael_unit":"mg/kg bw/day","noael_value":"= 7.2","page":24,"route":"oral","species":"rat","study_id":"sccp_o_027_noael_008"}
UnifiedCodex:SCCS_SHADOW:beta.noael_studies - =7.2 mg/kg bw/day rat oral - - SOURCE_SUBDIR=sccp_o_027; REPORT_TITLE=Opinion on Climbazole COLIPA n° P64; OPINION_NUMBER=SCCP/0918/05; COMMITTEE=SCCP; REPORT_DATE=20 September 2005; VALUE_TEXT== 7.2; DOSE=At the 36 mg/kg bw/day treatment level, the female rats exhibited slight-to-moderate toxicity during the initial stages of treatment with no observable effects on estrous or stillbirths.; EFFECT=es and an increased number of stillbirths. At the 36 mg/kg bw/day treatment level, the female rats exhibited slight-to-moderate toxicity during the initial stages of treatment with no observable effects on estrous or stillbirths. Embryotoxicity observed at 36 and 100 mg/kg bw/day consisted in decreased numbers of life pups at birth and was judged to be a secondary effect to maternal toxicity. Viewing the lack of full raw data, the following NOAEL values are proposed: NOAEL (maternal toxicity) = 7.2 mg/kg bw/day, NOAEL (embryotoxicity) = 36 mg/kg bw/day. Ref.: 87 3.3.8.2. Teratogenicity Teratogenicity study in the rabbit Guideline: OECD guideline no. 414 (adopted 22nd January 2001) Date of test : May-July 2001 Species/strain: Chinchilla rabbit Group size: 24 mated females Test substance: HR 00/600306 (Climbazole, purity min. 98%) Batch no.: 20072001 Dose levels: 0, 15, 30, 60 mg/kg bw/day Route: oral; gavage Exposure: days 6 through 27 of pregnancy GLP: in compliance Climbazole (indicated as HR 00/600306) was tested in a 4%; CITATION=Ref.: 87 3; CITATION_NUMBERS=[87,3]; REFERENCE=Ref.: 87 3; DETAILS_JSON={"cas_number":"38083-17-9","citation":"Ref.: 87 3","dose":"At the 36 mg/kg bw/day treatment level, the female rats exhibited slight-to-moderate toxicity during the initial stages of treatment with no observable effects on estrous or stillbirths.","duration":"","effect":"es and an increased number of stillbirths. At the 36 mg/kg bw/day treatment level, the female rats exhibited slight-to-moderate toxicity during the initial stages of treatment with no observable effects on estrous or stillbirths. Embryotoxicity observed at 36 and 100 mg/kg bw/day consisted in decreased numbers of life pups at birth and was judged to be a secondary effect to maternal toxicity. Viewing the lack of full raw data, the following NOAEL values are proposed: NOAEL (maternal toxicity) = 7.2 mg/kg bw/day, NOAEL (embryotoxicity) = 36 mg/kg bw/day. Ref.: 87 3.3.8.2. Teratogenicity Teratogenicity study in the rabbit Guideline: OECD guideline no. 414 (adopted 22nd January 2001) Date of test : May-July 2001 Species/strain: Chinchilla rabbit Group size: 24 mated females Test substance: HR 00/600306 (Climbazole, purity min. 98%) Batch no.: 20072001 Dose levels: 0, 15, 30, 60 mg/kg bw/day Route: oral; gavage Exposure: days 6 through 27 of pregnancy GLP: in compliance Climbazole (indicated as HR 00/600306) was tested in a 4%","endpoint":"","ingredient":"Climbazole","loael_value":"","noael_unit":"mg/kg bw/day","noael_value":"= 7.2","page":24,"route":"oral","species":"rat","study_id":"sccp_o_027_noael_009"}
UnifiedCodex:SCCS_SHADOW:beta.noael_studies - 5 mg/kg bw/day rat - 90-day - SOURCE_SUBDIR=sccs_o_120; REPORT_TITLE=ADDENDUM to the Opinion SCCS/1506/13 Climbazole Cosmetics Europe: P64; OPINION_NUMBER=SCCS/1506/13; COMMITTEE=Scientific Committee on Consumer Safety (SCCS); REPORT_DATE=18 June 2013; VALUE_TEXT=5; DOSE=5 mg/kg bw/day from the presented 90-day study with the rat.; EFFECT=Unlabeled table on page 6: 5 mg/kg bw/day from the presented 90-day study with the rat.; CITATION_NUMBERS=[]; DETAILS_JSON={"cas_number":"38083-17-9","citation":"","dose":"5 mg/kg bw/day from the presented 90-day study with the rat.","duration":"90-day","effect":"Unlabeled table on page 6: 5 mg/kg bw/day from the presented 90-day study with the rat.","endpoint":"","ingredient":"1-(4-chlorophenoxy)-1-imidazol-1-yl-3,3-dimethyl-2","loael_value":"","noael_unit":"mg/kg bw/day","noael_value":"5","page":6,"route":"","species":"rat","study_id":"sccs_o_120_noael_015"}
UnifiedCodex:SCCS_SHADOW:beta.noael_studies - 6 - - - - - SOURCE_SUBDIR=sccs_o_120; REPORT_TITLE=ADDENDUM to the Opinion SCCS/1506/13 Climbazole Cosmetics Europe: P64; OPINION_NUMBER=SCCS/1506/13; COMMITTEE=Scientific Committee on Consumer Safety (SCCS); REPORT_DATE=18 June 2013; VALUE_TEXT=unclear:Unlabeled table on page 6: descriptions and raw data, the SCCP deduced a conservative NOEL value of; EFFECT=Unlabeled table on page 6: descriptions and raw data, the SCCP deduced a conservative NOEL value of; CITATION_NUMBERS=[]; DETAILS_JSON={"cas_number":"38083-17-9","citation":"","dose":"","duration":"","effect":"Unlabeled table on page 6: descriptions and raw data, the SCCP deduced a conservative NOEL value of","endpoint":"","ingredient":"1-(4-chlorophenoxy)-1-imidazol-1-yl-3,3-dimethyl-2","loael_value":"","noael_unit":"","noael_value":"unclear:Unlabeled table on page 6: descriptions and raw data, the SCCP deduced a conservative NOEL value of","page":6,"route":"","species":"","study_id":"sccs_o_120_noael_014"}
UnifiedCodex:SCCS_SHADOW:beta.noael_studies dermal absorption 0.5 % rat oral 90 day dermal absorption SOURCE_SUBDIR=sccp_o_164; REPORT_TITLE=OPINION ON Climbazole COLIPA n° P64; OPINION_NUMBER=SCCP/1204/08; COMMITTEE=Scientific Committee on Consumer Products (SCCP); REPORT_DATE=21 January 2009; VALUE_TEXT=0.5; DOSE=se (SED) Ax0.001xSAS/60 = 0.026 mg/kg bw No observed effect level NOEL = 5 mg/kg bw/day (90 day, oral, rat) Margin of Safety NOEL / SED = 189 Calculation for the use of Climbazole at 0.5% in a cosmetic face cream Dermal absorption through human skin A (μg/cm2) = 1.25 µg/cm² Skin Area surface (1/2 head female) SAS (cm2) = 565 cm2 Typical body wei...; EFFECT=se (SED) Ax0.001xSAS/60 = 0.026 mg/kg bw No observed effect level NOEL = 5 mg/kg bw/day (90 day, oral, rat) Margin of Safety NOEL / SED = 189 Calculation for the use of Climbazole at 0.5% in a cosmetic face cream Dermal absorption through human skin A (μg/cm2) = 1.25 µg/cm² Skin Area surface (1/2 head female) SAS (cm2) = 565 cm2 Typical body weight of human = 60 kg Systemic exposure dose (SED) Ax0.001xSAS/60 = 0.012 mg/kg bw No observed effect level NOEL = 5 mg/kg bw/day (90 day, oral, rat) Margin of Safety NOEL / SED = 425 Calculation for the use of Climbazole at 0.5% in leave-on body lotion Dermal absorption through human skin A (μg/cm2) = 1.25 µg/cm² Skin Area surface (whole body) SAS (cm2) = 18,000 cm2 Typical body weight of human = 60 kg Systemic exposure dose (SED) Ax0.001xSAS/60 = 0.38 mg/kg bw No observed effect level NOEL = 5 mg/kg bw/day (90 day, oral, rat) Margin of Safety NOEL / SED = 13 3.3.14. Discussion Physico-chemical specifications The physico-chemical section has been updated and completed and; CITATION_NUMBERS=[]; DETAILS_JSON={"cas_number":"38083-17-9","citation":"","dose":"se (SED) Ax0.001xSAS/60 = 0.026 mg/kg bw No observed effect level NOEL = 5 mg/kg bw/day (90 day, oral, rat) Margin of Safety NOEL / SED = 189 Calculation for the use of Climbazole at 0.5% in a cosmetic face cream Dermal absorption through human skin A (μg/cm2) = 1.25 µg/cm² Skin Area surface (1/2 head female) SAS (cm2) = 565 cm2 Typical body wei...","duration":"90 day","effect":"se (SED) Ax0.001xSAS/60 = 0.026 mg/kg bw No observed effect level NOEL = 5 mg/kg bw/day (90 day, oral, rat) Margin of Safety NOEL / SED = 189 Calculation for the use of Climbazole at 0.5% in a cosmetic face cream Dermal absorption through human skin A (μg/cm2) = 1.25 µg/cm² Skin Area surface (1/2 head female) SAS (cm2) = 565 cm2 Typical body weight of human = 60 kg Systemic exposure dose (SED) Ax0.001xSAS/60 = 0.012 mg/kg bw No observed effect level NOEL = 5 mg/kg bw/day (90 day, oral, rat) Margin of Safety NOEL / SED = 425 Calculation for the use of Climbazole at 0.5% in leave-on body lotion Dermal absorption through human skin A (μg/cm2) = 1.25 µg/cm² Skin Area surface (whole body) SAS (cm2) = 18,000 cm2 Typical body weight of human = 60 kg Systemic exposure dose (SED) Ax0.001xSAS/60 = 0.38 mg/kg bw No observed effect level NOEL = 5 mg/kg bw/day (90 day, oral, rat) Margin of Safety NOEL / SED = 13 3.3.14. Discussion Physico-chemical specifications The physico-chemical section has been updated and completed and","endpoint":"dermal absorption","ingredient":"1-(4-chlorophenoxy)-1-imidazol-1-yl-3,3-dimethyl-2","loael_value":"","noael_unit":"%","noael_value":"0.5","page":24,"route":"oral","species":"rat","study_id":"sccp_o_164_noael_008"}
UnifiedCodex:SCCS_SHADOW:beta.noael_studies dermal absorption =5 mg/kg bw/day rat oral 90 day dermal absorption SOURCE_SUBDIR=sccp_o_164; REPORT_TITLE=OPINION ON Climbazole COLIPA n° P64; OPINION_NUMBER=SCCP/1204/08; COMMITTEE=Scientific Committee on Consumer Products (SCCP); REPORT_DATE=21 January 2009; VALUE_TEXT== 5; DOSE=Safety evaluation (including calculation of the MoS) Calculation of the Margin of Safety Calculation for the use of Climbazole at 2% as an anti-dandruff agent in shampoo Dermal absorption through human skin A (μg/cm2) = 0.297 µg/cm² Skin Area surface (hand + ½ head) SAS (cm2) = 1440 cm2 Typical body weight of human = 60 kg Systemic exposure dose...; EFFECT=test has been addressed in Section 3.3.2.1. 3.3.12. Special investigations No data submitted 3.3.13. Safety evaluation (including calculation of the MoS) Calculation of the Margin of Safety Calculation for the use of Climbazole at 2% as an anti-dandruff agent in shampoo Dermal absorption through human skin A (μg/cm2) = 0.297 µg/cm² Skin Area surface (hand + ½ head) SAS (cm2) = 1440 cm2 Typical body weight of human = 60 kg Systemic exposure dose (SED) Ax0.001xSAS/60 = 0.007 mg/kg bw No observed effect level NOEL = 5 mg/kg bw/day (90 day, oral, rat) Margin of Safety NOEL / SED = 701; CITATION_NUMBERS=[]; DETAILS_JSON={"cas_number":"38083-17-9","citation":"","dose":"Safety evaluation (including calculation of the MoS) Calculation of the Margin of Safety Calculation for the use of Climbazole at 2% as an anti-dandruff agent in shampoo Dermal absorption through human skin A (μg/cm2) = 0.297 µg/cm² Skin Area surface (hand + ½ head) SAS (cm2) = 1440 cm2 Typical body weight of human = 60 kg Systemic exposure dose...","duration":"90 day","effect":"test has been addressed in Section 3.3.2.1. 3.3.12. Special investigations No data submitted 3.3.13. Safety evaluation (including calculation of the MoS) Calculation of the Margin of Safety Calculation for the use of Climbazole at 2% as an anti-dandruff agent in shampoo Dermal absorption through human skin A (μg/cm2) = 0.297 µg/cm² Skin Area surface (hand + ½ head) SAS (cm2) = 1440 cm2 Typical body weight of human = 60 kg Systemic exposure dose (SED) Ax0.001xSAS/60 = 0.007 mg/kg bw No observed effect level NOEL = 5 mg/kg bw/day (90 day, oral, rat) Margin of Safety NOEL / SED = 701","endpoint":"dermal absorption","ingredient":"1-(4-chlorophenoxy)-1-imidazol-1-yl-3,3-dimethyl-2","loael_value":"","noael_unit":"mg/kg bw/day","noael_value":"= 5","page":23,"route":"oral","species":"rat","study_id":"sccp_o_164_noael_004"}
UnifiedCodex:SCCS_SHADOW:beta.noael_studies dermal absorption =5 mg/kg bw/day rat oral 90 day dermal absorption SOURCE_SUBDIR=sccp_o_164; REPORT_TITLE=OPINION ON Climbazole COLIPA n° P64; OPINION_NUMBER=SCCP/1204/08; COMMITTEE=Scientific Committee on Consumer Products (SCCP); REPORT_DATE=21 January 2009; VALUE_TEXT== 5; DOSE=Safety evaluation (including calculation of the MoS) Calculation of the Margin of Safety Calculation for the use of Climbazole at 2% as an anti-dandruff agent in shampoo Dermal absorption through human skin A (μg/cm2) = 0.297 µg/cm² Skin Area surface (hand + ½ head) SAS (cm2) = 1440 cm2 Typical body weight of human = 60 kg Systemic exposure dose...; EFFECT=l investigations No data submitted 3.3.13. Safety evaluation (including calculation of the MoS) Calculation of the Margin of Safety Calculation for the use of Climbazole at 2% as an anti-dandruff agent in shampoo Dermal absorption through human skin A (μg/cm2) = 0.297 µg/cm² Skin Area surface (hand + ½ head) SAS (cm2) = 1440 cm2 Typical body weight of human = 60 kg Systemic exposure dose (SED) Ax0.001xSAS/60 = 0.007 mg/kg bw No observed effect level NOEL = 5 mg/kg bw/day (90 day, oral, rat) Margin of Safety NOEL / SED = 701; CITATION_NUMBERS=[]; DETAILS_JSON={"cas_number":"38083-17-9","citation":"","dose":"Safety evaluation (including calculation of the MoS) Calculation of the Margin of Safety Calculation for the use of Climbazole at 2% as an anti-dandruff agent in shampoo Dermal absorption through human skin A (μg/cm2) = 0.297 µg/cm² Skin Area surface (hand + ½ head) SAS (cm2) = 1440 cm2 Typical body weight of human = 60 kg Systemic exposure dose...","duration":"90 day","effect":"l investigations No data submitted 3.3.13. Safety evaluation (including calculation of the MoS) Calculation of the Margin of Safety Calculation for the use of Climbazole at 2% as an anti-dandruff agent in shampoo Dermal absorption through human skin A (μg/cm2) = 0.297 µg/cm² Skin Area surface (hand + ½ head) SAS (cm2) = 1440 cm2 Typical body weight of human = 60 kg Systemic exposure dose (SED) Ax0.001xSAS/60 = 0.007 mg/kg bw No observed effect level NOEL = 5 mg/kg bw/day (90 day, oral, rat) Margin of Safety NOEL / SED = 701","endpoint":"dermal absorption","ingredient":"1-(4-chlorophenoxy)-1-imidazol-1-yl-3,3-dimethyl-2","loael_value":"","noael_unit":"mg/kg bw/day","noael_value":"= 5","page":23,"route":"oral","species":"rat","study_id":"sccp_o_164_noael_005"}
UnifiedCodex:SCCS_SHADOW:beta.noael_studies dermal absorption =5 mg/kg bw/day rat oral 90 day dermal absorption SOURCE_SUBDIR=sccp_o_164; REPORT_TITLE=OPINION ON Climbazole COLIPA n° P64; OPINION_NUMBER=SCCP/1204/08; COMMITTEE=Scientific Committee on Consumer Products (SCCP); REPORT_DATE=21 January 2009; VALUE_TEXT== 5; DOSE=SCCP/1204/08 Opinion on climbazole 24 Calculation for the use of Climbazole at 0.5% in aqueous hair lotions Dermal absorption through human skin A (μg/cm2) = 1.10 µg/cm² Skin Area surface (hand + ½ head) SAS (cm2) = 1440 cm2 Typical body weight of human = 60 kg Systemic exposure dose (SED) Ax0.001xSAS/60 = 0.026 mg/kg bw No observed effect level...; EFFECT=SCCP/1204/08 Opinion on climbazole 24 Calculation for the use of Climbazole at 0.5% in aqueous hair lotions Dermal absorption through human skin A (μg/cm2) = 1.10 µg/cm² Skin Area surface (hand + ½ head) SAS (cm2) = 1440 cm2 Typical body weight of human = 60 kg Systemic exposure dose (SED) Ax0.001xSAS/60 = 0.026 mg/kg bw No observed effect level NOEL = 5 mg/kg bw/day (90 day, oral, rat) Margin of Safety NOEL / SED = 189 Calculation for the use of Climbazole at 0.5% in a cosmetic face cream Dermal absorption through human skin A (μg/cm2) = 1.25 µg/cm² Skin Area surface (1/2 head female) SAS (cm2) = 565 cm2 Typical body weight of human = 60 kg Systemic exposure dose (SED) Ax0.001xSAS/60 = 0.012 mg/kg bw No observed effect level NOEL = 5 mg/kg bw/day (90 day, oral, rat) Margin of Safety NOEL / SED = 425 Calculation for the use of Climbazole at 0.5% in l; CITATION_NUMBERS=[]; DETAILS_JSON={"cas_number":"38083-17-9","citation":"","dose":"SCCP/1204/08 Opinion on climbazole 24 Calculation for the use of Climbazole at 0.5% in aqueous hair lotions Dermal absorption through human skin A (μg/cm2) = 1.10 µg/cm² Skin Area surface (hand + ½ head) SAS (cm2) = 1440 cm2 Typical body weight of human = 60 kg Systemic exposure dose (SED) Ax0.001xSAS/60 = 0.026 mg/kg bw No observed effect level...","duration":"90 day","effect":"SCCP/1204/08 Opinion on climbazole 24 Calculation for the use of Climbazole at 0.5% in aqueous hair lotions Dermal absorption through human skin A (μg/cm2) = 1.10 µg/cm² Skin Area surface (hand + ½ head) SAS (cm2) = 1440 cm2 Typical body weight of human = 60 kg Systemic exposure dose (SED) Ax0.001xSAS/60 = 0.026 mg/kg bw No observed effect level NOEL = 5 mg/kg bw/day (90 day, oral, rat) Margin of Safety NOEL / SED = 189 Calculation for the use of Climbazole at 0.5% in a cosmetic face cream Dermal absorption through human skin A (μg/cm2) = 1.25 µg/cm² Skin Area surface (1/2 head female) SAS (cm2) = 565 cm2 Typical body weight of human = 60 kg Systemic exposure dose (SED) Ax0.001xSAS/60 = 0.012 mg/kg bw No observed effect level NOEL = 5 mg/kg bw/day (90 day, oral, rat) Margin of Safety NOEL / SED = 425 Calculation for the use of Climbazole at 0.5% in l","endpoint":"dermal absorption","ingredient":"1-(4-chlorophenoxy)-1-imidazol-1-yl-3,3-dimethyl-2","loael_value":"","noael_unit":"mg/kg bw/day","noael_value":"= 5","page":24,"route":"oral","species":"rat","study_id":"sccp_o_164_noael_006"}
UnifiedCodex:SCCS_SHADOW:beta.noael_studies dermal absorption =5 mg/kg bw/day rat oral 90 day dermal absorption SOURCE_SUBDIR=sccp_o_164; REPORT_TITLE=OPINION ON Climbazole COLIPA n° P64; OPINION_NUMBER=SCCP/1204/08; COMMITTEE=Scientific Committee on Consumer Products (SCCP); REPORT_DATE=21 January 2009; VALUE_TEXT== 5; DOSE=2 Typical body weight of human = 60 kg Systemic exposure dose (SED) Ax0.001xSAS/60 = 0.026 mg/kg bw No observed effect level NOEL = 5 mg/kg bw/day (90 day, oral, rat) Margin of Safety NOEL / SED = 189 Calculation for the use of Climbazole at 0.5% in a cosmetic face cream Dermal absorption through human skin A (μg/cm2) = 1.25 µg/cm² Skin Area sur...; EFFECT=2 Typical body weight of human = 60 kg Systemic exposure dose (SED) Ax0.001xSAS/60 = 0.026 mg/kg bw No observed effect level NOEL = 5 mg/kg bw/day (90 day, oral, rat) Margin of Safety NOEL / SED = 189 Calculation for the use of Climbazole at 0.5% in a cosmetic face cream Dermal absorption through human skin A (μg/cm2) = 1.25 µg/cm² Skin Area surface (1/2 head female) SAS (cm2) = 565 cm2 Typical body weight of human = 60 kg Systemic exposure dose (SED) Ax0.001xSAS/60 = 0.012 mg/kg bw No observed effect level NOEL = 5 mg/kg bw/day (90 day, oral, rat) Margin of Safety NOEL / SED = 425 Calculation for the use of Climbazole at 0.5% in leave-on body lotion Dermal absorption through human skin A (μg/cm2) = 1.25 µg/cm² Skin Area surface (whole body) SAS (cm2) = 18,000 cm2 Typical body weight of human = 60 kg Systemic exposure dose (SED) Ax0.001xSAS/60 = 0.38 mg/kg bw No observed effect level NOEL = 5 mg/kg bw/day (90 day, oral, rat) Margin of Safety NOEL / SED = 13 3.3.14. Discussion Physico-chemical specifications The; CITATION_NUMBERS=[]; DETAILS_JSON={"cas_number":"38083-17-9","citation":"","dose":"2 Typical body weight of human = 60 kg Systemic exposure dose (SED) Ax0.001xSAS/60 = 0.026 mg/kg bw No observed effect level NOEL = 5 mg/kg bw/day (90 day, oral, rat) Margin of Safety NOEL / SED = 189 Calculation for the use of Climbazole at 0.5% in a cosmetic face cream Dermal absorption through human skin A (μg/cm2) = 1.25 µg/cm² Skin Area sur...","duration":"90 day","effect":"2 Typical body weight of human = 60 kg Systemic exposure dose (SED) Ax0.001xSAS/60 = 0.026 mg/kg bw No observed effect level NOEL = 5 mg/kg bw/day (90 day, oral, rat) Margin of Safety NOEL / SED = 189 Calculation for the use of Climbazole at 0.5% in a cosmetic face cream Dermal absorption through human skin A (μg/cm2) = 1.25 µg/cm² Skin Area surface (1/2 head female) SAS (cm2) = 565 cm2 Typical body weight of human = 60 kg Systemic exposure dose (SED) Ax0.001xSAS/60 = 0.012 mg/kg bw No observed effect level NOEL = 5 mg/kg bw/day (90 day, oral, rat) Margin of Safety NOEL / SED = 425 Calculation for the use of Climbazole at 0.5% in leave-on body lotion Dermal absorption through human skin A (μg/cm2) = 1.25 µg/cm² Skin Area surface (whole body) SAS (cm2) = 18,000 cm2 Typical body weight of human = 60 kg Systemic exposure dose (SED) Ax0.001xSAS/60 = 0.38 mg/kg bw No observed effect level NOEL = 5 mg/kg bw/day (90 day, oral, rat) Margin of Safety NOEL / SED = 13 3.3.14. Discussion Physico-chemical specifications The","endpoint":"dermal absorption","ingredient":"1-(4-chlorophenoxy)-1-imidazol-1-yl-3,3-dimethyl-2","loael_value":"","noael_unit":"mg/kg bw/day","noael_value":"= 5","page":24,"route":"oral","species":"rat","study_id":"sccp_o_164_noael_007"}
UnifiedCodex:SCCS_SHADOW:beta.noael_studies dermal absorption =5 mg/kg bw/day rat oral 90 day dermal absorption SOURCE_SUBDIR=sccp_o_164; REPORT_TITLE=OPINION ON Climbazole COLIPA n° P64; OPINION_NUMBER=SCCP/1204/08; COMMITTEE=Scientific Committee on Consumer Products (SCCP); REPORT_DATE=21 January 2009; VALUE_TEXT== 5; DOSE=5 cm2 Typical body weight of human = 60 kg Systemic exposure dose (SED) Ax0.001xSAS/60 = 0.012 mg/kg bw No observed effect level NOEL = 5 mg/kg bw/day (90 day, oral, rat) Margin of Safety NOEL / SED = 425 Calculation for the use of Climbazole at 0.5% in leave-on body lotion Dermal absorption through human skin A (μg/cm2) = 1.25 µg/cm² Skin Area...; EFFECT=5 cm2 Typical body weight of human = 60 kg Systemic exposure dose (SED) Ax0.001xSAS/60 = 0.012 mg/kg bw No observed effect level NOEL = 5 mg/kg bw/day (90 day, oral, rat) Margin of Safety NOEL / SED = 425 Calculation for the use of Climbazole at 0.5% in leave-on body lotion Dermal absorption through human skin A (μg/cm2) = 1.25 µg/cm² Skin Area surface (whole body) SAS (cm2) = 18,000 cm2 Typical body weight of human = 60 kg Systemic exposure dose (SED) Ax0.001xSAS/60 = 0.38 mg/kg bw No observed effect level NOEL = 5 mg/kg bw/day (90 day, oral, rat) Margin of Safety NOEL / SED = 13 3.3.14. Discussion Physico-chemical specifications The physico-chemical section has been updated and completed and can now be accepted. Irritation / sensitisation The previous results of an old Draize eye test and a combination of two newly carried out in vitro screening tests for eye irritation (HET-CAM and CEET) suggest that Climbazole is not an eye irritant. Its potential to cause skin irritation is assessed through a human single patch; CITATION_NUMBERS=[]; DETAILS_JSON={"cas_number":"38083-17-9","citation":"","dose":"5 cm2 Typical body weight of human = 60 kg Systemic exposure dose (SED) Ax0.001xSAS/60 = 0.012 mg/kg bw No observed effect level NOEL = 5 mg/kg bw/day (90 day, oral, rat) Margin of Safety NOEL / SED = 425 Calculation for the use of Climbazole at 0.5% in leave-on body lotion Dermal absorption through human skin A (μg/cm2) = 1.25 µg/cm² Skin Area...","duration":"90 day","effect":"5 cm2 Typical body weight of human = 60 kg Systemic exposure dose (SED) Ax0.001xSAS/60 = 0.012 mg/kg bw No observed effect level NOEL = 5 mg/kg bw/day (90 day, oral, rat) Margin of Safety NOEL / SED = 425 Calculation for the use of Climbazole at 0.5% in leave-on body lotion Dermal absorption through human skin A (μg/cm2) = 1.25 µg/cm² Skin Area surface (whole body) SAS (cm2) = 18,000 cm2 Typical body weight of human = 60 kg Systemic exposure dose (SED) Ax0.001xSAS/60 = 0.38 mg/kg bw No observed effect level NOEL = 5 mg/kg bw/day (90 day, oral, rat) Margin of Safety NOEL / SED = 13 3.3.14. Discussion Physico-chemical specifications The physico-chemical section has been updated and completed and can now be accepted. Irritation / sensitisation The previous results of an old Draize eye test and a combination of two newly carried out in vitro screening tests for eye irritation (HET-CAM and CEET) suggest that Climbazole is not an eye irritant. Its potential to cause skin irritation is assessed through a human single patch","endpoint":"dermal absorption","ingredient":"1-(4-chlorophenoxy)-1-imidazol-1-yl-3,3-dimethyl-2","loael_value":"","noael_unit":"mg/kg bw/day","noael_value":"= 5","page":24,"route":"oral","species":"rat","study_id":"sccp_o_164_noael_009"}
UnifiedCodex:SCCS_SHADOW:beta.noael_studies dermal absorption =5 mg/kg bw/day rat oral 90 day dermal absorption SOURCE_SUBDIR=sccp_o_164; REPORT_TITLE=OPINION ON Climbazole COLIPA n° P64; OPINION_NUMBER=SCCP/1204/08; COMMITTEE=Scientific Committee on Consumer Products (SCCP); REPORT_DATE=21 January 2009; VALUE_TEXT== 5; DOSE=e dose (SED) Ax0.001xSAS/60 = 0.012 mg/kg bw No observed effect level NOEL = 5 mg/kg bw/day (90 day, oral, rat) Margin of Safety NOEL / SED = 425 Calculation for the use of Climbazole at 0.5% in leave-on body lotion Dermal absorption through human skin A (μg/cm2) = 1.25 µg/cm² Skin Area surface (whole body) SAS (cm2) = 18,000 cm2 Typical body we...; EFFECT=e dose (SED) Ax0.001xSAS/60 = 0.012 mg/kg bw No observed effect level NOEL = 5 mg/kg bw/day (90 day, oral, rat) Margin of Safety NOEL / SED = 425 Calculation for the use of Climbazole at 0.5% in leave-on body lotion Dermal absorption through human skin A (μg/cm2) = 1.25 µg/cm² Skin Area surface (whole body) SAS (cm2) = 18,000 cm2 Typical body weight of human = 60 kg Systemic exposure dose (SED) Ax0.001xSAS/60 = 0.38 mg/kg bw No observed effect level NOEL = 5 mg/kg bw/day (90 day, oral, rat) Margin of Safety NOEL / SED = 13 3.3.14. Discussion Physico-chemical specifications The physico-chemical section has been updated and completed and can now be accepted. Irritation / sensitisation The previous results of an old Draize eye test and a combination of two newly carried out in vitro screening tests for eye irritation (HET-CAM and CEET) suggest that Climbazole is not an eye irritant. Its potential to cause skin irritation is assessed through a human single patch test and shows only mild to no skin irritation. Considering; CITATION_NUMBERS=[]; DETAILS_JSON={"cas_number":"38083-17-9","citation":"","dose":"e dose (SED) Ax0.001xSAS/60 = 0.012 mg/kg bw No observed effect level NOEL = 5 mg/kg bw/day (90 day, oral, rat) Margin of Safety NOEL / SED = 425 Calculation for the use of Climbazole at 0.5% in leave-on body lotion Dermal absorption through human skin A (μg/cm2) = 1.25 µg/cm² Skin Area surface (whole body) SAS (cm2) = 18,000 cm2 Typical body we...","duration":"90 day","effect":"e dose (SED) Ax0.001xSAS/60 = 0.012 mg/kg bw No observed effect level NOEL = 5 mg/kg bw/day (90 day, oral, rat) Margin of Safety NOEL / SED = 425 Calculation for the use of Climbazole at 0.5% in leave-on body lotion Dermal absorption through human skin A (μg/cm2) = 1.25 µg/cm² Skin Area surface (whole body) SAS (cm2) = 18,000 cm2 Typical body weight of human = 60 kg Systemic exposure dose (SED) Ax0.001xSAS/60 = 0.38 mg/kg bw No observed effect level NOEL = 5 mg/kg bw/day (90 day, oral, rat) Margin of Safety NOEL / SED = 13 3.3.14. Discussion Physico-chemical specifications The physico-chemical section has been updated and completed and can now be accepted. Irritation / sensitisation The previous results of an old Draize eye test and a combination of two newly carried out in vitro screening tests for eye irritation (HET-CAM and CEET) suggest that Climbazole is not an eye irritant. Its potential to cause skin irritation is assessed through a human single patch test and shows only mild to no skin irritation. Considering","endpoint":"dermal absorption","ingredient":"1-(4-chlorophenoxy)-1-imidazol-1-yl-3,3-dimethyl-2","loael_value":"","noael_unit":"mg/kg bw/day","noael_value":"= 5","page":24,"route":"oral","species":"rat","study_id":"sccp_o_164_noael_010"}
UnifiedCodex:SCCS_SHADOW:beta.noael_studies dermal absorption 5 mg/kg bw/day mouse oral - dermal absorption SOURCE_SUBDIR=sccp_o_164; REPORT_TITLE=OPINION ON Climbazole COLIPA n° P64; OPINION_NUMBER=SCCP/1204/08; COMMITTEE=Scientific Committee on Consumer Products (SCCP); REPORT_DATE=21 January 2009; VALUE_TEXT=5; DOSE=Calculation of the Margin of Safety Taking into account the mean values measured in the scientifically acceptable in vitro dermal absorption study for the use of Climbazole in a shampoo (rinse-off), together with the conservative NOEL value of 5 mg/kg bw/day, the MoS calculated for the use of Climbazole as anti-dandruff agent at 2% in cosmetic s...; EFFECT=bw/day. Toxicokinetics A newly performed oral bioavailability assay of 14C Climbazole in mice confirms the results that were described earlier, namely that Climbazole is rapidly absorbed and excreted and that its maximum concentration in plasma is reached after approximately 8 hours. Calculation of the Margin of Safety Taking into account the mean values measured in the scientifically acceptable in vitro dermal absorption study for the use of Climbazole in a shampoo (rinse-off), together with the conservative NOEL value of 5 mg/kg bw/day, the MoS calculated for the use of Climbazole as anti-dandruff agent at 2% in cosmetic shampoos, is above 100. For the leave-on applications, the calculations show that the use of Climbazole at 0.5% in an aqueous hair lotion and in a face cream, can be considered safe, as the MoS's are 189 and 425, respectively. The use of Climbazole at 0.5% for whole body applications, however, generates a MoS of 13. To generate an acceptable MoS (≥ 100), the treated surface area for leave-on products cont; CITATION_NUMBERS=[]; DETAILS_JSON={"cas_number":"38083-17-9","citation":"","dose":"Calculation of the Margin of Safety Taking into account the mean values measured in the scientifically acceptable in vitro dermal absorption study for the use of Climbazole in a shampoo (rinse-off), together with the conservative NOEL value of 5 mg/kg bw/day, the MoS calculated for the use of Climbazole as anti-dandruff agent at 2% in cosmetic s...","duration":"","effect":"bw/day. Toxicokinetics A newly performed oral bioavailability assay of 14C Climbazole in mice confirms the results that were described earlier, namely that Climbazole is rapidly absorbed and excreted and that its maximum concentration in plasma is reached after approximately 8 hours. Calculation of the Margin of Safety Taking into account the mean values measured in the scientifically acceptable in vitro dermal absorption study for the use of Climbazole in a shampoo (rinse-off), together with the conservative NOEL value of 5 mg/kg bw/day, the MoS calculated for the use of Climbazole as anti-dandruff agent at 2% in cosmetic shampoos, is above 100. For the leave-on applications, the calculations show that the use of Climbazole at 0.5% in an aqueous hair lotion and in a face cream, can be considered safe, as the MoS's are 189 and 425, respectively. The use of Climbazole at 0.5% for whole body applications, however, generates a MoS of 13. To generate an acceptable MoS (≥ 100), the treated surface area for leave-on products cont","endpoint":"dermal absorption","ingredient":"1-(4-chlorophenoxy)-1-imidazol-1-yl-3,3-dimethyl-2","loael_value":"","noael_unit":"mg/kg bw/day","noael_value":"5","page":25,"route":"oral","species":"mouse","study_id":"sccp_o_164_noael_014"}
UnifiedCodex:SCCS_SHADOW:beta.noael_studies dermal absorption =5 mg/kg bw/day rat oral 90 day dermal absorption SOURCE_SUBDIR=sccs_o_120; REPORT_TITLE=ADDENDUM to the Opinion SCCS/1506/13 Climbazole Cosmetics Europe: P64; OPINION_NUMBER=SCCS/1506/13; COMMITTEE=Scientific Committee on Consumer Safety (SCCS); REPORT_DATE=18 June 2013; VALUE_TEXT== 5; DOSE=ndum to the opinion on climbazole ___________________________________________________________________________________________ 7 3.1.2 MoS calculations and SCCP conclusions Calculation for the use of Climbazole at 2% as an anti-dandruff agent in shampoo Dermal absorption through human skin A (μg/cm²) = 0.297 µg/cm² Skin Area surface (area hand +...; EFFECT=ndum to the opinion on climbazole ___________________________________________________________________________________________ 7 3.1.2 MoS calculations and SCCP conclusions Calculation for the use of Climbazole at 2% as an anti-dandruff agent in shampoo Dermal absorption through human skin A (μg/cm²) = 0.297 µg/cm² Skin Area surface (area hand + ½ area head) SAS (cm²) = 1440 cm² Typical human body weight = 60 kg Systemic exposure dose (SED) A x (10-3mg/µg) x SAS / 60 kg = 0.007 mg/kg bw No observed effect level NOEL = 5 mg/kg bw/day (90 day, oral, rat) Margin of Safety NOEL / SED = 701 Calculation for the use of Climbazole as preservative at 0.5% in aqueous hair lotions Dermal absorption through human skin A (μg/cm²) = 1.10 µg/cm² Skin Area surface (area hand + ½ area head) SAS (cm²) = 1440 cm² Typical human body weight = 60 kg Systemic exposure dose (SED) A x (10-3mg/µg) x SAS / 60 kg = 0.026 mg/kg bw No observed effect level NOEL = 5 mg/kg bw/day (90 day, oral, rat) Margin of Safety NOEL / SED = 189 Calculation for t; CITATION_NUMBERS=[]; DETAILS_JSON={"cas_number":"38083-17-9","citation":"","dose":"ndum to the opinion on climbazole ___________________________________________________________________________________________ 7 3.1.2 MoS calculations and SCCP conclusions Calculation for the use of Climbazole at 2% as an anti-dandruff agent in shampoo Dermal absorption through human skin A (μg/cm²) = 0.297 µg/cm² Skin Area surface (area hand +...","duration":"90 day","effect":"ndum to the opinion on climbazole ___________________________________________________________________________________________ 7 3.1.2 MoS calculations and SCCP conclusions Calculation for the use of Climbazole at 2% as an anti-dandruff agent in shampoo Dermal absorption through human skin A (μg/cm²) = 0.297 µg/cm² Skin Area surface (area hand + ½ area head) SAS (cm²) = 1440 cm² Typical human body weight = 60 kg Systemic exposure dose (SED) A x (10-3mg/µg) x SAS / 60 kg = 0.007 mg/kg bw No observed effect level NOEL = 5 mg/kg bw/day (90 day, oral, rat) Margin of Safety NOEL / SED = 701 Calculation for the use of Climbazole as preservative at 0.5% in aqueous hair lotions Dermal absorption through human skin A (μg/cm²) = 1.10 µg/cm² Skin Area surface (area hand + ½ area head) SAS (cm²) = 1440 cm² Typical human body weight = 60 kg Systemic exposure dose (SED) A x (10-3mg/µg) x SAS / 60 kg = 0.026 mg/kg bw No observed effect level NOEL = 5 mg/kg bw/day (90 day, oral, rat) Margin of Safety NOEL / SED = 189 Calculation for t","endpoint":"dermal absorption","ingredient":"1-(4-chlorophenoxy)-1-imidazol-1-yl-3,3-dimethyl-2","loael_value":"","noael_unit":"mg/kg bw/day","noael_value":"= 5","page":7,"route":"oral","species":"rat","study_id":"sccs_o_120_noael_004"}
UnifiedCodex:SCCS_SHADOW:beta.noael_studies dermal absorption =5 mg/kg bw/day rat oral 90 day dermal absorption SOURCE_SUBDIR=sccs_o_120; REPORT_TITLE=ADDENDUM to the Opinion SCCS/1506/13 Climbazole Cosmetics Europe: P64; OPINION_NUMBER=SCCS/1506/13; COMMITTEE=Scientific Committee on Consumer Safety (SCCS); REPORT_DATE=18 June 2013; VALUE_TEXT== 5; DOSE=_________________________________________________________________ 7 3.1.2 MoS calculations and SCCP conclusions Calculation for the use of Climbazole at 2% as an anti-dandruff agent in shampoo Dermal absorption through human skin A (μg/cm²) = 0.297 µg/cm² Skin Area surface (area hand + ½ area head) SAS (cm²) = 1440 cm² Typical human body weight...; EFFECT=_________________________________________________________________ 7 3.1.2 MoS calculations and SCCP conclusions Calculation for the use of Climbazole at 2% as an anti-dandruff agent in shampoo Dermal absorption through human skin A (μg/cm²) = 0.297 µg/cm² Skin Area surface (area hand + ½ area head) SAS (cm²) = 1440 cm² Typical human body weight = 60 kg Systemic exposure dose (SED) A x (10-3mg/µg) x SAS / 60 kg = 0.007 mg/kg bw No observed effect level NOEL = 5 mg/kg bw/day (90 day, oral, rat) Margin of Safety NOEL / SED = 701 Calculation for the use of Climbazole as preservative at 0.5% in aqueous hair lotions Dermal absorption through human skin A (μg/cm²) = 1.10 µg/cm² Skin Area surface (area hand + ½ area head) SAS (cm²) = 1440 cm² Typical human body weight = 60 kg Systemic exposure dose (SED) A x (10-3mg/µg) x SAS / 60 kg = 0.026 mg/kg bw No observed effect level NOEL = 5 mg/kg bw/day (90 day, oral, rat) Margin of Safety NOEL / SED = 189 Calculation for the use of Climbazole as preservative at 0.5% in a cosmetic f; CITATION_NUMBERS=[]; DETAILS_JSON={"cas_number":"38083-17-9","citation":"","dose":"_________________________________________________________________ 7 3.1.2 MoS calculations and SCCP conclusions Calculation for the use of Climbazole at 2% as an anti-dandruff agent in shampoo Dermal absorption through human skin A (μg/cm²) = 0.297 µg/cm² Skin Area surface (area hand + ½ area head) SAS (cm²) = 1440 cm² Typical human body weight...","duration":"90 day","effect":"_________________________________________________________________ 7 3.1.2 MoS calculations and SCCP conclusions Calculation for the use of Climbazole at 2% as an anti-dandruff agent in shampoo Dermal absorption through human skin A (μg/cm²) = 0.297 µg/cm² Skin Area surface (area hand + ½ area head) SAS (cm²) = 1440 cm² Typical human body weight = 60 kg Systemic exposure dose (SED) A x (10-3mg/µg) x SAS / 60 kg = 0.007 mg/kg bw No observed effect level NOEL = 5 mg/kg bw/day (90 day, oral, rat) Margin of Safety NOEL / SED = 701 Calculation for the use of Climbazole as preservative at 0.5% in aqueous hair lotions Dermal absorption through human skin A (μg/cm²) = 1.10 µg/cm² Skin Area surface (area hand + ½ area head) SAS (cm²) = 1440 cm² Typical human body weight = 60 kg Systemic exposure dose (SED) A x (10-3mg/µg) x SAS / 60 kg = 0.026 mg/kg bw No observed effect level NOEL = 5 mg/kg bw/day (90 day, oral, rat) Margin of Safety NOEL / SED = 189 Calculation for the use of Climbazole as preservative at 0.5% in a cosmetic f","endpoint":"dermal absorption","ingredient":"1-(4-chlorophenoxy)-1-imidazol-1-yl-3,3-dimethyl-2","loael_value":"","noael_unit":"mg/kg bw/day","noael_value":"= 5","page":7,"route":"oral","species":"rat","study_id":"sccs_o_120_noael_005"}
UnifiedCodex:SCCS_SHADOW:beta.noael_studies dermal absorption =5 mg/kg bw/day rat oral 90 day dermal absorption SOURCE_SUBDIR=sccs_o_120; REPORT_TITLE=ADDENDUM to the Opinion SCCS/1506/13 Climbazole Cosmetics Europe: P64; OPINION_NUMBER=SCCS/1506/13; COMMITTEE=Scientific Committee on Consumer Safety (SCCS); REPORT_DATE=18 June 2013; VALUE_TEXT== 5; DOSE=exposure dose (SED) A x (10-3mg/µg) x SAS / 60 kg = 0.007 mg/kg bw No observed effect level NOEL = 5 mg/kg bw/day (90 day, oral, rat) Margin of Safety NOEL / SED = 701 Calculation for the use of Climbazole as preservative at 0.5% in aqueous hair lotions Dermal absorption through human skin A (μg/cm²) = 1.10 µg/cm² Skin Area surface (area hand +...; EFFECT=exposure dose (SED) A x (10-3mg/µg) x SAS / 60 kg = 0.007 mg/kg bw No observed effect level NOEL = 5 mg/kg bw/day (90 day, oral, rat) Margin of Safety NOEL / SED = 701 Calculation for the use of Climbazole as preservative at 0.5% in aqueous hair lotions Dermal absorption through human skin A (μg/cm²) = 1.10 µg/cm² Skin Area surface (area hand + ½ area head) SAS (cm²) = 1440 cm² Typical human body weight = 60 kg Systemic exposure dose (SED) A x (10-3mg/µg) x SAS / 60 kg = 0.026 mg/kg bw No observed effect level NOEL = 5 mg/kg bw/day (90 day, oral, rat) Margin of Safety NOEL / SED = 189 Calculation for the use of Climbazole as preservative at 0.5% in a cosmetic face cream Dermal absorption through human skin A (μg/cm²) = 1.25 µg/cm² Skin Area surface (1/2 area head female) SAS (cm²) = 565 cm² Typical human body weight = 60 kg Systemic exposure dose (SED) A x (10-3mg/µg) x SAS / 60 kg = 0.012 mg/kg bw No observed effect level NOEL = 5 mg/kg bw/day (90 day, oral, rat) Margin of Safety NOEL / SED = 425 Calculation for the; CITATION_NUMBERS=[]; DETAILS_JSON={"cas_number":"38083-17-9","citation":"","dose":"exposure dose (SED) A x (10-3mg/µg) x SAS / 60 kg = 0.007 mg/kg bw No observed effect level NOEL = 5 mg/kg bw/day (90 day, oral, rat) Margin of Safety NOEL / SED = 701 Calculation for the use of Climbazole as preservative at 0.5% in aqueous hair lotions Dermal absorption through human skin A (μg/cm²) = 1.10 µg/cm² Skin Area surface (area hand +...","duration":"90 day","effect":"exposure dose (SED) A x (10-3mg/µg) x SAS / 60 kg = 0.007 mg/kg bw No observed effect level NOEL = 5 mg/kg bw/day (90 day, oral, rat) Margin of Safety NOEL / SED = 701 Calculation for the use of Climbazole as preservative at 0.5% in aqueous hair lotions Dermal absorption through human skin A (μg/cm²) = 1.10 µg/cm² Skin Area surface (area hand + ½ area head) SAS (cm²) = 1440 cm² Typical human body weight = 60 kg Systemic exposure dose (SED) A x (10-3mg/µg) x SAS / 60 kg = 0.026 mg/kg bw No observed effect level NOEL = 5 mg/kg bw/day (90 day, oral, rat) Margin of Safety NOEL / SED = 189 Calculation for the use of Climbazole as preservative at 0.5% in a cosmetic face cream Dermal absorption through human skin A (μg/cm²) = 1.25 µg/cm² Skin Area surface (1/2 area head female) SAS (cm²) = 565 cm² Typical human body weight = 60 kg Systemic exposure dose (SED) A x (10-3mg/µg) x SAS / 60 kg = 0.012 mg/kg bw No observed effect level NOEL = 5 mg/kg bw/day (90 day, oral, rat) Margin of Safety NOEL / SED = 425 Calculation for the","endpoint":"dermal absorption","ingredient":"1-(4-chlorophenoxy)-1-imidazol-1-yl-3,3-dimethyl-2","loael_value":"","noael_unit":"mg/kg bw/day","noael_value":"= 5","page":7,"route":"oral","species":"rat","study_id":"sccs_o_120_noael_006"}
UnifiedCodex:SCCS_SHADOW:beta.noael_studies dermal absorption =5 mg/kg bw/day rat oral 90 day dermal absorption SOURCE_SUBDIR=sccs_o_120; REPORT_TITLE=ADDENDUM to the Opinion SCCS/1506/13 Climbazole Cosmetics Europe: P64; OPINION_NUMBER=SCCS/1506/13; COMMITTEE=Scientific Committee on Consumer Safety (SCCS); REPORT_DATE=18 June 2013; VALUE_TEXT== 5; DOSE=/kg bw No observed effect level NOEL = 5 mg/kg bw/day (90 day, oral, rat) Margin of Safety NOEL / SED = 701 Calculation for the use of Climbazole as preservative at 0.5% in aqueous hair lotions Dermal absorption through human skin A (μg/cm²) = 1.10 µg/cm² Skin Area surface (area hand + ½ area head) SAS (cm²) = 1440 cm² Typical human body weight...; EFFECT=/kg bw No observed effect level NOEL = 5 mg/kg bw/day (90 day, oral, rat) Margin of Safety NOEL / SED = 701 Calculation for the use of Climbazole as preservative at 0.5% in aqueous hair lotions Dermal absorption through human skin A (μg/cm²) = 1.10 µg/cm² Skin Area surface (area hand + ½ area head) SAS (cm²) = 1440 cm² Typical human body weight = 60 kg Systemic exposure dose (SED) A x (10-3mg/µg) x SAS / 60 kg = 0.026 mg/kg bw No observed effect level NOEL = 5 mg/kg bw/day (90 day, oral, rat) Margin of Safety NOEL / SED = 189 Calculation for the use of Climbazole as preservative at 0.5% in a cosmetic face cream Dermal absorption through human skin A (μg/cm²) = 1.25 µg/cm² Skin Area surface (1/2 area head female) SAS (cm²) = 565 cm² Typical human body weight = 60 kg Systemic exposure dose (SED) A x (10-3mg/µg) x SAS / 60 kg = 0.012 mg/kg bw No observed effect level NOEL = 5 mg/kg bw/day (90 day, oral, rat) Margin of Safety NOEL / SED = 425 Calculation for the use of Climbazole as preservative at 0.5% in leave-on body l; CITATION_NUMBERS=[]; DETAILS_JSON={"cas_number":"38083-17-9","citation":"","dose":"/kg bw No observed effect level NOEL = 5 mg/kg bw/day (90 day, oral, rat) Margin of Safety NOEL / SED = 701 Calculation for the use of Climbazole as preservative at 0.5% in aqueous hair lotions Dermal absorption through human skin A (μg/cm²) = 1.10 µg/cm² Skin Area surface (area hand + ½ area head) SAS (cm²) = 1440 cm² Typical human body weight...","duration":"90 day","effect":"/kg bw No observed effect level NOEL = 5 mg/kg bw/day (90 day, oral, rat) Margin of Safety NOEL / SED = 701 Calculation for the use of Climbazole as preservative at 0.5% in aqueous hair lotions Dermal absorption through human skin A (μg/cm²) = 1.10 µg/cm² Skin Area surface (area hand + ½ area head) SAS (cm²) = 1440 cm² Typical human body weight = 60 kg Systemic exposure dose (SED) A x (10-3mg/µg) x SAS / 60 kg = 0.026 mg/kg bw No observed effect level NOEL = 5 mg/kg bw/day (90 day, oral, rat) Margin of Safety NOEL / SED = 189 Calculation for the use of Climbazole as preservative at 0.5% in a cosmetic face cream Dermal absorption through human skin A (μg/cm²) = 1.25 µg/cm² Skin Area surface (1/2 area head female) SAS (cm²) = 565 cm² Typical human body weight = 60 kg Systemic exposure dose (SED) A x (10-3mg/µg) x SAS / 60 kg = 0.012 mg/kg bw No observed effect level NOEL = 5 mg/kg bw/day (90 day, oral, rat) Margin of Safety NOEL / SED = 425 Calculation for the use of Climbazole as preservative at 0.5% in leave-on body l","endpoint":"dermal absorption","ingredient":"1-(4-chlorophenoxy)-1-imidazol-1-yl-3,3-dimethyl-2","loael_value":"","noael_unit":"mg/kg bw/day","noael_value":"= 5","page":7,"route":"oral","species":"rat","study_id":"sccs_o_120_noael_007"}
UnifiedCodex:SCCS_SHADOW:beta.noael_studies dermal absorption =5 mg/kg bw/day rat oral 90 day dermal absorption SOURCE_SUBDIR=sccs_o_120; REPORT_TITLE=ADDENDUM to the Opinion SCCS/1506/13 Climbazole Cosmetics Europe: P64; OPINION_NUMBER=SCCS/1506/13; COMMITTEE=Scientific Committee on Consumer Safety (SCCS); REPORT_DATE=18 June 2013; VALUE_TEXT== 5; DOSE=ic exposure dose (SED) A x (10-3mg/µg) x SAS / 60 kg = 0.026 mg/kg bw No observed effect level NOEL = 5 mg/kg bw/day (90 day, oral, rat) Margin of Safety NOEL / SED = 189 Calculation for the use of Climbazole as preservative at 0.5% in a cosmetic face cream Dermal absorption through human skin A (μg/cm²) = 1.25 µg/cm² Skin Area surface (1/2 area...; EFFECT=ic exposure dose (SED) A x (10-3mg/µg) x SAS / 60 kg = 0.026 mg/kg bw No observed effect level NOEL = 5 mg/kg bw/day (90 day, oral, rat) Margin of Safety NOEL / SED = 189 Calculation for the use of Climbazole as preservative at 0.5% in a cosmetic face cream Dermal absorption through human skin A (μg/cm²) = 1.25 µg/cm² Skin Area surface (1/2 area head female) SAS (cm²) = 565 cm² Typical human body weight = 60 kg Systemic exposure dose (SED) A x (10-3mg/µg) x SAS / 60 kg = 0.012 mg/kg bw No observed effect level NOEL = 5 mg/kg bw/day (90 day, oral, rat) Margin of Safety NOEL / SED = 425 Calculation for the use of Climbazole as preservative at 0.5% in leave-on body lotion Dermal absorption through human skin A (μg/cm²) = 1.25 µg/cm² Skin Area surface (whole body) SAS (cm²) = 18,000 cm² Typical human body weight = 60 kg Systemic exposure dose (SED) A x (10-3mg/µg) x SAS / 60 kg = 0.38 mg/kg bw No observed effect level NOEL = 5 mg/kg bw/day (90 day, oral, rat) Margin of Safety NOEL / SED = 13; CITATION_NUMBERS=[]; DETAILS_JSON={"cas_number":"38083-17-9","citation":"","dose":"ic exposure dose (SED) A x (10-3mg/µg) x SAS / 60 kg = 0.026 mg/kg bw No observed effect level NOEL = 5 mg/kg bw/day (90 day, oral, rat) Margin of Safety NOEL / SED = 189 Calculation for the use of Climbazole as preservative at 0.5% in a cosmetic face cream Dermal absorption through human skin A (μg/cm²) = 1.25 µg/cm² Skin Area surface (1/2 area...","duration":"90 day","effect":"ic exposure dose (SED) A x (10-3mg/µg) x SAS / 60 kg = 0.026 mg/kg bw No observed effect level NOEL = 5 mg/kg bw/day (90 day, oral, rat) Margin of Safety NOEL / SED = 189 Calculation for the use of Climbazole as preservative at 0.5% in a cosmetic face cream Dermal absorption through human skin A (μg/cm²) = 1.25 µg/cm² Skin Area surface (1/2 area head female) SAS (cm²) = 565 cm² Typical human body weight = 60 kg Systemic exposure dose (SED) A x (10-3mg/µg) x SAS / 60 kg = 0.012 mg/kg bw No observed effect level NOEL = 5 mg/kg bw/day (90 day, oral, rat) Margin of Safety NOEL / SED = 425 Calculation for the use of Climbazole as preservative at 0.5% in leave-on body lotion Dermal absorption through human skin A (μg/cm²) = 1.25 µg/cm² Skin Area surface (whole body) SAS (cm²) = 18,000 cm² Typical human body weight = 60 kg Systemic exposure dose (SED) A x (10-3mg/µg) x SAS / 60 kg = 0.38 mg/kg bw No observed effect level NOEL = 5 mg/kg bw/day (90 day, oral, rat) Margin of Safety NOEL / SED = 13","endpoint":"dermal absorption","ingredient":"1-(4-chlorophenoxy)-1-imidazol-1-yl-3,3-dimethyl-2","loael_value":"","noael_unit":"mg/kg bw/day","noael_value":"= 5","page":7,"route":"oral","species":"rat","study_id":"sccs_o_120_noael_008"}
UnifiedCodex:SCCS_SHADOW:beta.noael_studies dermal absorption =5 mg/kg bw/day rat oral 90 day dermal absorption SOURCE_SUBDIR=sccs_o_120; REPORT_TITLE=ADDENDUM to the Opinion SCCS/1506/13 Climbazole Cosmetics Europe: P64; OPINION_NUMBER=SCCS/1506/13; COMMITTEE=Scientific Committee on Consumer Safety (SCCS); REPORT_DATE=18 June 2013; VALUE_TEXT== 5; DOSE=mg/kg bw No observed effect level NOEL = 5 mg/kg bw/day (90 day, oral, rat) Margin of Safety NOEL / SED = 189 Calculation for the use of Climbazole as preservative at 0.5% in a cosmetic face cream Dermal absorption through human skin A (μg/cm²) = 1.25 µg/cm² Skin Area surface (1/2 area head female) SAS (cm²) = 565 cm² Typical human body weight =...; EFFECT=mg/kg bw No observed effect level NOEL = 5 mg/kg bw/day (90 day, oral, rat) Margin of Safety NOEL / SED = 189 Calculation for the use of Climbazole as preservative at 0.5% in a cosmetic face cream Dermal absorption through human skin A (μg/cm²) = 1.25 µg/cm² Skin Area surface (1/2 area head female) SAS (cm²) = 565 cm² Typical human body weight = 60 kg Systemic exposure dose (SED) A x (10-3mg/µg) x SAS / 60 kg = 0.012 mg/kg bw No observed effect level NOEL = 5 mg/kg bw/day (90 day, oral, rat) Margin of Safety NOEL / SED = 425 Calculation for the use of Climbazole as preservative at 0.5% in leave-on body lotion Dermal absorption through human skin A (μg/cm²) = 1.25 µg/cm² Skin Area surface (whole body) SAS (cm²) = 18,000 cm² Typical human body weight = 60 kg Systemic exposure dose (SED) A x (10-3mg/µg) x SAS / 60 kg = 0.38 mg/kg bw No observed effect level NOEL = 5 mg/kg bw/day (90 day, oral, rat) Margin of Safety NOEL / SED = 13; CITATION_NUMBERS=[]; DETAILS_JSON={"cas_number":"38083-17-9","citation":"","dose":"mg/kg bw No observed effect level NOEL = 5 mg/kg bw/day (90 day, oral, rat) Margin of Safety NOEL / SED = 189 Calculation for the use of Climbazole as preservative at 0.5% in a cosmetic face cream Dermal absorption through human skin A (μg/cm²) = 1.25 µg/cm² Skin Area surface (1/2 area head female) SAS (cm²) = 565 cm² Typical human body weight =...","duration":"90 day","effect":"mg/kg bw No observed effect level NOEL = 5 mg/kg bw/day (90 day, oral, rat) Margin of Safety NOEL / SED = 189 Calculation for the use of Climbazole as preservative at 0.5% in a cosmetic face cream Dermal absorption through human skin A (μg/cm²) = 1.25 µg/cm² Skin Area surface (1/2 area head female) SAS (cm²) = 565 cm² Typical human body weight = 60 kg Systemic exposure dose (SED) A x (10-3mg/µg) x SAS / 60 kg = 0.012 mg/kg bw No observed effect level NOEL = 5 mg/kg bw/day (90 day, oral, rat) Margin of Safety NOEL / SED = 425 Calculation for the use of Climbazole as preservative at 0.5% in leave-on body lotion Dermal absorption through human skin A (μg/cm²) = 1.25 µg/cm² Skin Area surface (whole body) SAS (cm²) = 18,000 cm² Typical human body weight = 60 kg Systemic exposure dose (SED) A x (10-3mg/µg) x SAS / 60 kg = 0.38 mg/kg bw No observed effect level NOEL = 5 mg/kg bw/day (90 day, oral, rat) Margin of Safety NOEL / SED = 13","endpoint":"dermal absorption","ingredient":"1-(4-chlorophenoxy)-1-imidazol-1-yl-3,3-dimethyl-2","loael_value":"","noael_unit":"mg/kg bw/day","noael_value":"= 5","page":7,"route":"oral","species":"rat","study_id":"sccs_o_120_noael_009"}
UnifiedCodex:SCCS_SHADOW:beta.noael_studies dermal absorption =5 mg/kg bw/day rat oral 90 day dermal absorption SOURCE_SUBDIR=sccs_o_120; REPORT_TITLE=ADDENDUM to the Opinion SCCS/1506/13 Climbazole Cosmetics Europe: P64; OPINION_NUMBER=SCCS/1506/13; COMMITTEE=Scientific Committee on Consumer Safety (SCCS); REPORT_DATE=18 June 2013; VALUE_TEXT== 5; DOSE=kg Systemic exposure dose (SED) A x (10-3mg/µg) x SAS / 60 kg = 0.012 mg/kg bw No observed effect level NOEL = 5 mg/kg bw/day (90 day, oral, rat) Margin of Safety NOEL / SED = 425 Calculation for the use of Climbazole as preservative at 0.5% in leave-on body lotion Dermal absorption through human skin A (μg/cm²) = 1.25 µg/cm² Skin Area surface (...; EFFECT=kg Systemic exposure dose (SED) A x (10-3mg/µg) x SAS / 60 kg = 0.012 mg/kg bw No observed effect level NOEL = 5 mg/kg bw/day (90 day, oral, rat) Margin of Safety NOEL / SED = 425 Calculation for the use of Climbazole as preservative at 0.5% in leave-on body lotion Dermal absorption through human skin A (μg/cm²) = 1.25 µg/cm² Skin Area surface (whole body) SAS (cm²) = 18,000 cm² Typical human body weight = 60 kg Systemic exposure dose (SED) A x (10-3mg/µg) x SAS / 60 kg = 0.38 mg/kg bw No observed effect level NOEL = 5 mg/kg bw/day (90 day, oral, rat) Margin of Safety NOEL / SED = 13; CITATION_NUMBERS=[]; DETAILS_JSON={"cas_number":"38083-17-9","citation":"","dose":"kg Systemic exposure dose (SED) A x (10-3mg/µg) x SAS / 60 kg = 0.012 mg/kg bw No observed effect level NOEL = 5 mg/kg bw/day (90 day, oral, rat) Margin of Safety NOEL / SED = 425 Calculation for the use of Climbazole as preservative at 0.5% in leave-on body lotion Dermal absorption through human skin A (μg/cm²) = 1.25 µg/cm² Skin Area surface (...","duration":"90 day","effect":"kg Systemic exposure dose (SED) A x (10-3mg/µg) x SAS / 60 kg = 0.012 mg/kg bw No observed effect level NOEL = 5 mg/kg bw/day (90 day, oral, rat) Margin of Safety NOEL / SED = 425 Calculation for the use of Climbazole as preservative at 0.5% in leave-on body lotion Dermal absorption through human skin A (μg/cm²) = 1.25 µg/cm² Skin Area surface (whole body) SAS (cm²) = 18,000 cm² Typical human body weight = 60 kg Systemic exposure dose (SED) A x (10-3mg/µg) x SAS / 60 kg = 0.38 mg/kg bw No observed effect level NOEL = 5 mg/kg bw/day (90 day, oral, rat) Margin of Safety NOEL / SED = 13","endpoint":"dermal absorption","ingredient":"1-(4-chlorophenoxy)-1-imidazol-1-yl-3,3-dimethyl-2","loael_value":"","noael_unit":"mg/kg bw/day","noael_value":"= 5","page":7,"route":"oral","species":"rat","study_id":"sccs_o_120_noael_010"}
UnifiedCodex:SCCS_SHADOW:beta.noael_studies dermal absorption =5 mg/kg bw/day rat oral 90 day dermal absorption SOURCE_SUBDIR=sccs_o_120; REPORT_TITLE=ADDENDUM to the Opinion SCCS/1506/13 Climbazole Cosmetics Europe: P64; OPINION_NUMBER=SCCS/1506/13; COMMITTEE=Scientific Committee on Consumer Safety (SCCS); REPORT_DATE=18 June 2013; VALUE_TEXT== 5; DOSE=g = 0.012 mg/kg bw No observed effect level NOEL = 5 mg/kg bw/day (90 day, oral, rat) Margin of Safety NOEL / SED = 425 Calculation for the use of Climbazole as preservative at 0.5% in leave-on body lotion Dermal absorption through human skin A (μg/cm²) = 1.25 µg/cm² Skin Area surface (whole body) SAS (cm²) = 18,000 cm² Typical human body weight...; EFFECT=g = 0.012 mg/kg bw No observed effect level NOEL = 5 mg/kg bw/day (90 day, oral, rat) Margin of Safety NOEL / SED = 425 Calculation for the use of Climbazole as preservative at 0.5% in leave-on body lotion Dermal absorption through human skin A (μg/cm²) = 1.25 µg/cm² Skin Area surface (whole body) SAS (cm²) = 18,000 cm² Typical human body weight = 60 kg Systemic exposure dose (SED) A x (10-3mg/µg) x SAS / 60 kg = 0.38 mg/kg bw No observed effect level NOEL = 5 mg/kg bw/day (90 day, oral, rat) Margin of Safety NOEL / SED = 13; CITATION_NUMBERS=[]; DETAILS_JSON={"cas_number":"38083-17-9","citation":"","dose":"g = 0.012 mg/kg bw No observed effect level NOEL = 5 mg/kg bw/day (90 day, oral, rat) Margin of Safety NOEL / SED = 425 Calculation for the use of Climbazole as preservative at 0.5% in leave-on body lotion Dermal absorption through human skin A (μg/cm²) = 1.25 µg/cm² Skin Area surface (whole body) SAS (cm²) = 18,000 cm² Typical human body weight...","duration":"90 day","effect":"g = 0.012 mg/kg bw No observed effect level NOEL = 5 mg/kg bw/day (90 day, oral, rat) Margin of Safety NOEL / SED = 425 Calculation for the use of Climbazole as preservative at 0.5% in leave-on body lotion Dermal absorption through human skin A (μg/cm²) = 1.25 µg/cm² Skin Area surface (whole body) SAS (cm²) = 18,000 cm² Typical human body weight = 60 kg Systemic exposure dose (SED) A x (10-3mg/µg) x SAS / 60 kg = 0.38 mg/kg bw No observed effect level NOEL = 5 mg/kg bw/day (90 day, oral, rat) Margin of Safety NOEL / SED = 13","endpoint":"dermal absorption","ingredient":"1-(4-chlorophenoxy)-1-imidazol-1-yl-3,3-dimethyl-2","loael_value":"","noael_unit":"mg/kg bw/day","noael_value":"= 5","page":7,"route":"oral","species":"rat","study_id":"sccs_o_120_noael_011"}
UnifiedCodex:SCCS_SHADOW:beta.noael_studies dermal absorption =5 mg/kg bw/day rat oral 90 day dermal absorption SOURCE_SUBDIR=sccs_o_120; REPORT_TITLE=ADDENDUM to the Opinion SCCS/1506/13 Climbazole Cosmetics Europe: P64; OPINION_NUMBER=SCCS/1506/13; COMMITTEE=Scientific Committee on Consumer Safety (SCCS); REPORT_DATE=18 June 2013; VALUE_TEXT== 5; DOSE=2) SAS (cm2) = 1170 cm2 Typical human body weight = 60 kg Systemic exposure dose (SED) A x (10-3mg/µg) x SAS / 60 kg = 0.024 mg/kg bw No observed effect level NOEL = 5 mg/kg bw/day (90 day, oral, rat) Margin of Safety NOEL / SED = 205 The applicant proposes to use the same dermal absorption value as found for a leave-on body lotion, as foot care...; EFFECT=plicant requests the extension of the use of Climbazole as preservative to foot care products. The following calculation of the MoS for that particular application is as follows: Calculation for the use of Climbazole as preservative up to 0.5% in foot care products Dermal absorption through human skin A (μg/cm2) = 1.25 µg/cm² Skin Area surface (feet, Ref. 2) SAS (cm2) = 1170 cm2 Typical human body weight = 60 kg Systemic exposure dose (SED) A x (10-3mg/µg) x SAS / 60 kg = 0.024 mg/kg bw No observed effect level NOEL = 5 mg/kg bw/day (90 day, oral, rat) Margin of Safety NOEL / SED = 205 The applicant proposes to use the same dermal absorption value as found for a leave-on body lotion, as foot care products have a closely related composition. In addition, it is pointed out that the MoS is further enhanced by differences between body areas like the volar forearm, scalp and face and the plantar region of the feet. The relation regarding percutaneous penetration of hydrocortisone through human skin is stated to be typically 1.0; CITATION_NUMBERS=[]; DETAILS_JSON={"cas_number":"38083-17-9","citation":"","dose":"2) SAS (cm2) = 1170 cm2 Typical human body weight = 60 kg Systemic exposure dose (SED) A x (10-3mg/µg) x SAS / 60 kg = 0.024 mg/kg bw No observed effect level NOEL = 5 mg/kg bw/day (90 day, oral, rat) Margin of Safety NOEL / SED = 205 The applicant proposes to use the same dermal absorption value as found for a leave-on body lotion, as foot care...","duration":"90 day","effect":"plicant requests the extension of the use of Climbazole as preservative to foot care products. The following calculation of the MoS for that particular application is as follows: Calculation for the use of Climbazole as preservative up to 0.5% in foot care products Dermal absorption through human skin A (μg/cm2) = 1.25 µg/cm² Skin Area surface (feet, Ref. 2) SAS (cm2) = 1170 cm2 Typical human body weight = 60 kg Systemic exposure dose (SED) A x (10-3mg/µg) x SAS / 60 kg = 0.024 mg/kg bw No observed effect level NOEL = 5 mg/kg bw/day (90 day, oral, rat) Margin of Safety NOEL / SED = 205 The applicant proposes to use the same dermal absorption value as found for a leave-on body lotion, as foot care products have a closely related composition. In addition, it is pointed out that the MoS is further enhanced by differences between body areas like the volar forearm, scalp and face and the plantar region of the feet. The relation regarding percutaneous penetration of hydrocortisone through human skin is stated to be typically 1.0","endpoint":"dermal absorption","ingredient":"1-(4-chlorophenoxy)-1-imidazol-1-yl-3,3-dimethyl-2","loael_value":"","noael_unit":"mg/kg bw/day","noael_value":"= 5","page":8,"route":"oral","species":"rat","study_id":"sccs_o_120_noael_012"}
UnifiedCodex:SCCS_SHADOW:beta.noael_studies dermal absorption =5 mg/kg bw/day rat oral 90 day dermal absorption SOURCE_SUBDIR=sccs_o_120; REPORT_TITLE=ADDENDUM to the Opinion SCCS/1506/13 Climbazole Cosmetics Europe: P64; OPINION_NUMBER=SCCS/1506/13; COMMITTEE=Scientific Committee on Consumer Safety (SCCS); REPORT_DATE=18 June 2013; VALUE_TEXT== 5; DOSE=2) SAS (cm2) = 1170 cm2 Typical human body weight = 60 kg Systemic exposure dose (SED) A x (10-3mg/µg) x SAS / 60 kg = 0.024 mg/kg bw No observed effect level NOEL = 5 mg/kg bw/day (90 day, oral, rat) Margin of Safety NOEL / SED = 205 The applicant proposes to use the same dermal absorption value as found for a leave-on body lotion, as foot care...; EFFECT=reservative to foot care products. The following calculation of the MoS for that particular application is as follows: Calculation for the use of Climbazole as preservative up to 0.5% in foot care products Dermal absorption through human skin A (μg/cm2) = 1.25 µg/cm² Skin Area surface (feet, Ref. 2) SAS (cm2) = 1170 cm2 Typical human body weight = 60 kg Systemic exposure dose (SED) A x (10-3mg/µg) x SAS / 60 kg = 0.024 mg/kg bw No observed effect level NOEL = 5 mg/kg bw/day (90 day, oral, rat) Margin of Safety NOEL / SED = 205 The applicant proposes to use the same dermal absorption value as found for a leave-on body lotion, as foot care products have a closely related composition. In addition, it is pointed out that the MoS is further enhanced by differences between body areas like the volar forearm, scalp and face and the plantar region of the feet. The relation regarding percutaneous penetration of hydrocortisone through human skin is stated to be typically 1.0 for the volar forearm and 0.14 for the plantar sole/arch (Re; CITATION_NUMBERS=[]; DETAILS_JSON={"cas_number":"38083-17-9","citation":"","dose":"2) SAS (cm2) = 1170 cm2 Typical human body weight = 60 kg Systemic exposure dose (SED) A x (10-3mg/µg) x SAS / 60 kg = 0.024 mg/kg bw No observed effect level NOEL = 5 mg/kg bw/day (90 day, oral, rat) Margin of Safety NOEL / SED = 205 The applicant proposes to use the same dermal absorption value as found for a leave-on body lotion, as foot care...","duration":"90 day","effect":"reservative to foot care products. The following calculation of the MoS for that particular application is as follows: Calculation for the use of Climbazole as preservative up to 0.5% in foot care products Dermal absorption through human skin A (μg/cm2) = 1.25 µg/cm² Skin Area surface (feet, Ref. 2) SAS (cm2) = 1170 cm2 Typical human body weight = 60 kg Systemic exposure dose (SED) A x (10-3mg/µg) x SAS / 60 kg = 0.024 mg/kg bw No observed effect level NOEL = 5 mg/kg bw/day (90 day, oral, rat) Margin of Safety NOEL / SED = 205 The applicant proposes to use the same dermal absorption value as found for a leave-on body lotion, as foot care products have a closely related composition. In addition, it is pointed out that the MoS is further enhanced by differences between body areas like the volar forearm, scalp and face and the plantar region of the feet. The relation regarding percutaneous penetration of hydrocortisone through human skin is stated to be typically 1.0 for the volar forearm and 0.14 for the plantar sole/arch (Re","endpoint":"dermal absorption","ingredient":"1-(4-chlorophenoxy)-1-imidazol-1-yl-3,3-dimethyl-2","loael_value":"","noael_unit":"mg/kg bw/day","noael_value":"= 5","page":8,"route":"oral","species":"rat","study_id":"sccs_o_120_noael_013"}
UnifiedCodex:SCCS_SHADOW:beta.noael_studies developmental toxicity 30 mg/kg bw/day rat oral - developmental toxicity SOURCE_SUBDIR=sccp_o_027; REPORT_TITLE=Opinion on Climbazole COLIPA n° P64; OPINION_NUMBER=SCCP/0918/05; COMMITTEE=SCCP; REPORT_DATE=20 September 2005; VALUE_TEXT=30; DOSE=the highest dose group.; EFFECT=the highest dose group. This difference in sex ratio was not considered to be test item-related. Examination of viscera, skeleton, and cartilage revealed no Climbazole-related foetal abnormalities. Conclusion No teratogenic effects were observed in this study with rabbits. Maternal toxicity (alopecia, reduced weight gain) was seen at 30 and 60 mg/kg bw/day. Embryotoxic effects (increased post- implantational losses) seen in the highest dose group are considered to be secondary to the effects on dams. The proposed NOAEL (embryotoxicity) is 30 mg/kg bw/day. Based on maternal toxicity at the two higher doses, 15 mg/kg bw/day is considered a NOAEL for maternal toxicity. Ref.: 17 Teratogenicity study in the rat (1) Guideline: teratogenicity study (1981) according to guidelines at the time Species/strain: BAY: FB30 rat Group size: 25 inseminated females Test substance: BAY e 6975 (Climbazole, purity not stated) Batch no.: 570327 Dose levels: 0, 10, 30, 100 mg/kg bw/day Route: oral; gavage Exposure: days 6 to 15 of pregnancy, inclusi; CITATION=Ref.: 17 Teratogenicity study in the rat (1) Guideline: teratogenicity study (1981) according to guidelines at the time Species/strain: BAY: FB30 rat Group size: 25 inseminated females T; CITATION_NUMBERS=[17,1,1981,30,25]; REFERENCE=Ref.: 17 Teratogenicity study in the rat (1) Guideline: teratogenicity study (1981) according to guidelines at the time Species/strain: BAY: FB30 rat Group size: 25 inseminated females T; DETAILS_JSON={"cas_number":"38083-17-9","citation":"Ref.: 17 Teratogenicity study in the rat (1) Guideline: teratogenicity study (1981) according to guidelines at the time Species/strain: BAY: FB30 rat Group size: 25 inseminated females T","dose":"the highest dose group.","duration":"","effect":"the highest dose group. This difference in sex ratio was not considered to be test item-related. Examination of viscera, skeleton, and cartilage revealed no Climbazole-related foetal abnormalities. Conclusion No teratogenic effects were observed in this study with rabbits. Maternal toxicity (alopecia, reduced weight gain) was seen at 30 and 60 mg/kg bw/day. Embryotoxic effects (increased post- implantational losses) seen in the highest dose group are considered to be secondary to the effects on dams. The proposed NOAEL (embryotoxicity) is 30 mg/kg bw/day. Based on maternal toxicity at the two higher doses, 15 mg/kg bw/day is considered a NOAEL for maternal toxicity. Ref.: 17 Teratogenicity study in the rat (1) Guideline: teratogenicity study (1981) according to guidelines at the time Species/strain: BAY: FB30 rat Group size: 25 inseminated females Test substance: BAY e 6975 (Climbazole, purity not stated) Batch no.: 570327 Dose levels: 0, 10, 30, 100 mg/kg bw/day Route: oral; gavage Exposure: days 6 to 15 of pregnancy, inclusi","endpoint":"developmental toxicity","ingredient":"Climbazole","loael_value":"","noael_unit":"mg/kg bw/day","noael_value":"30","page":25,"route":"oral","species":"rat","study_id":"sccp_o_027_noael_010"}
UnifiedCodex:SCCS_SHADOW:beta.noael_studies developmental toxicity 15 mg/kg bw/day rat oral 6 to day developmental toxicity SOURCE_SUBDIR=sccp_o_027; REPORT_TITLE=Opinion on Climbazole COLIPA n° P64; OPINION_NUMBER=SCCP/0918/05; COMMITTEE=SCCP; REPORT_DATE=20 September 2005; VALUE_TEXT=15; DOSE=Maternal toxicity (alopecia, reduced weight gain) was seen at 30 and 60 mg/kg bw/day.; EFFECT=on, and cartilage revealed no Climbazole-related foetal abnormalities. Conclusion No teratogenic effects were observed in this study with rabbits. Maternal toxicity (alopecia, reduced weight gain) was seen at 30 and 60 mg/kg bw/day. Embryotoxic effects (increased post- implantational losses) seen in the highest dose group are considered to be secondary to the effects on dams. The proposed NOAEL (embryotoxicity) is 30 mg/kg bw/day. Based on maternal toxicity at the two higher doses, 15 mg/kg bw/day is considered a NOAEL for maternal toxicity. Ref.: 17 Teratogenicity study in the rat (1) Guideline: teratogenicity study (1981) according to guidelines at the time Species/strain: BAY: FB30 rat Group size: 25 inseminated females Test substance: BAY e 6975 (Climbazole, purity not stated) Batch no.: 570327 Dose levels: 0, 10, 30, 100 mg/kg bw/day Route: oral; gavage Exposure: days 6 to 15 of pregnancy, inclusive GLP: no information (test performed in 1981, prior to GLP regulations) Climbazole was administered daily from day 6 to day; CITATION=Ref.: 17 Teratogenicity study in the rat (1) Guideline: teratogenicity study (1981) according to guidelines at the time Species/strain: BAY: FB30 rat Group size: 25 inseminated females T; CITATION_NUMBERS=[17,1,1981,30,25]; REFERENCE=Ref.: 17 Teratogenicity study in the rat (1) Guideline: teratogenicity study (1981) according to guidelines at the time Species/strain: BAY: FB30 rat Group size: 25 inseminated females T; DETAILS_JSON={"cas_number":"38083-17-9","citation":"Ref.: 17 Teratogenicity study in the rat (1) Guideline: teratogenicity study (1981) according to guidelines at the time Species/strain: BAY: FB30 rat Group size: 25 inseminated females T","dose":"Maternal toxicity (alopecia, reduced weight gain) was seen at 30 and 60 mg/kg bw/day.","duration":"6 to day","effect":"on, and cartilage revealed no Climbazole-related foetal abnormalities. Conclusion No teratogenic effects were observed in this study with rabbits. Maternal toxicity (alopecia, reduced weight gain) was seen at 30 and 60 mg/kg bw/day. Embryotoxic effects (increased post- implantational losses) seen in the highest dose group are considered to be secondary to the effects on dams. The proposed NOAEL (embryotoxicity) is 30 mg/kg bw/day. Based on maternal toxicity at the two higher doses, 15 mg/kg bw/day is considered a NOAEL for maternal toxicity. Ref.: 17 Teratogenicity study in the rat (1) Guideline: teratogenicity study (1981) according to guidelines at the time Species/strain: BAY: FB30 rat Group size: 25 inseminated females Test substance: BAY e 6975 (Climbazole, purity not stated) Batch no.: 570327 Dose levels: 0, 10, 30, 100 mg/kg bw/day Route: oral; gavage Exposure: days 6 to 15 of pregnancy, inclusive GLP: no information (test performed in 1981, prior to GLP regulations) Climbazole was administered daily from day 6 to day","endpoint":"developmental toxicity","ingredient":"Climbazole","loael_value":"","noael_unit":"mg/kg bw/day","noael_value":"15","page":25,"route":"oral","species":"rat","study_id":"sccp_o_027_noael_011"}
UnifiedCodex:SCCS_SHADOW:beta.noael_studies developmental toxicity 10 mg/kg rat - - developmental toxicity SOURCE_SUBDIR=sccp_o_027; REPORT_TITLE=Opinion on Climbazole COLIPA n° P64; OPINION_NUMBER=SCCP/0918/05; COMMITTEE=SCCP; REPORT_DATE=20 September 2005; VALUE_TEXT=10; DOSE=The laboratory concludes that no signs of teratogenic effects were seen in this teratogenicity study with rats with applied doses of 10 to 100 mg/kg during gestation days 6 through 15.; EFFECT=ticular study appear to be reliable. Conclusion The study was neither conducted in full compliance with the respective current OECD Guideline, nor has formal adherence to GLP principles been documented and reported. This makes the results difficult to interpret, especially in the case of such a specialised area as teratogenicity. The laboratory concludes that no signs of teratogenic effects were seen in this teratogenicity study with rats with applied doses of 10 to 100 mg/kg during gestation days 6 through 15. A NOAEL of 10 mg/kg has been identified for maternal toxicity. Embryotoxic effects were observed at 100 mg/kg and were judged to be secondary effects to the maternal toxicity. Ref.: 16 Teratogenicity study in the rat (2) Guideline: teratogenicity study (1979) according to guidelines at the time Species/strain: Charles River CD® rat Group size: 25 inseminated females Test substance: Compound No. 34054 (Climbazole, purity not stated); CITATION=Ref.: 16 Teratogenicity study in the rat (2) Guideline: teratogenicity study (1979) according to guidelines at the time Species/strain: Charles River CD® rat Group size: 25 inseminated f; CITATION_NUMBERS=[16,2,1979,25]; REFERENCE=Ref.: 16 Teratogenicity study in the rat (2) Guideline: teratogenicity study (1979) according to guidelines at the time Species/strain: Charles River CD® rat Group size: 25 inseminated f; DETAILS_JSON={"cas_number":"38083-17-9","citation":"Ref.: 16 Teratogenicity study in the rat (2) Guideline: teratogenicity study (1979) according to guidelines at the time Species/strain: Charles River CD® rat Group size: 25 inseminated f","dose":"The laboratory concludes that no signs of teratogenic effects were seen in this teratogenicity study with rats with applied doses of 10 to 100 mg/kg during gestation days 6 through 15.","duration":"","effect":"ticular study appear to be reliable. Conclusion The study was neither conducted in full compliance with the respective current OECD Guideline, nor has formal adherence to GLP principles been documented and reported. This makes the results difficult to interpret, especially in the case of such a specialised area as teratogenicity. The laboratory concludes that no signs of teratogenic effects were seen in this teratogenicity study with rats with applied doses of 10 to 100 mg/kg during gestation days 6 through 15. A NOAEL of 10 mg/kg has been identified for maternal toxicity. Embryotoxic effects were observed at 100 mg/kg and were judged to be secondary effects to the maternal toxicity. Ref.: 16 Teratogenicity study in the rat (2) Guideline: teratogenicity study (1979) according to guidelines at the time Species/strain: Charles River CD® rat Group size: 25 inseminated females Test substance: Compound No. 34054 (Climbazole, purity not stated)","endpoint":"developmental toxicity","ingredient":"Climbazole","loael_value":"","noael_unit":"mg/kg","noael_value":"10","page":26,"route":"","species":"rat","study_id":"sccp_o_027_noael_012"}
UnifiedCodex:SCCS_SHADOW:beta.noael_studies developmental toxicity 7.2 mg/kg rat - - developmental toxicity SOURCE_SUBDIR=sccp_o_027; REPORT_TITLE=Opinion on Climbazole COLIPA n° P64; OPINION_NUMBER=SCCP/0918/05; COMMITTEE=SCCP; REPORT_DATE=20 September 2005; VALUE_TEXT=7.2; DOSE=The authors conclude that skeletal variations have been observed in pups at maternal doses of 36 and 100 mg/kg bw/day.; EFFECT=velopmental toxicity study was neither conducted in full compliance with the respective current OECD Guideline, nor has formal adherence to GLP principles been documented and reported. The lack of the full raw data package makes the results difficult to interpret. The authors conclude that skeletal variations have been observed in pups at maternal doses of 36 and 100 mg/kg bw/day. Maternal toxicity was obvious at 36 and 100 mg/kg bw/day, 4 dams died at the highest dose. The lowest dose (7.2mg/kg) was found to be a NOAEL. There were no clear- cut indications of specific teratogenic effects at any dose level. Ref.: 85 Additional studies The dossier contains a teratogenicity study from 1977, in which only one dosage level (100 mg/kg bw/day) was tested. Viewing the restricted aim (dose-range finding study) and the age of the study, it is not discussed in detail. Ref.: 31 Finally, a so-called "peri-/postnatal toxicity study" is provided, in which 20 inseminated female rats were administered Compound N°34054 (Climbazole, purity not; CITATION=Ref.: 85 Additional studies The dossier contains a teratogenicity study from 1977, in which only one dosage level (100 mg/kg bw/day) was tested; CITATION_NUMBERS=[85,1977,100]; REFERENCE=Ref.: 85 Additional studies The dossier contains a teratogenicity study from 1977, in which only one dosage level (100 mg/kg bw/day) was tested; DETAILS_JSON={"cas_number":"38083-17-9","citation":"Ref.: 85 Additional studies The dossier contains a teratogenicity study from 1977, in which only one dosage level (100 mg/kg bw/day) was tested","dose":"The authors conclude that skeletal variations have been observed in pups at maternal doses of 36 and 100 mg/kg bw/day.","duration":"","effect":"velopmental toxicity study was neither conducted in full compliance with the respective current OECD Guideline, nor has formal adherence to GLP principles been documented and reported. The lack of the full raw data package makes the results difficult to interpret. The authors conclude that skeletal variations have been observed in pups at maternal doses of 36 and 100 mg/kg bw/day. Maternal toxicity was obvious at 36 and 100 mg/kg bw/day, 4 dams died at the highest dose. The lowest dose (7.2mg/kg) was found to be a NOAEL. There were no clear- cut indications of specific teratogenic effects at any dose level. Ref.: 85 Additional studies The dossier contains a teratogenicity study from 1977, in which only one dosage level (100 mg/kg bw/day) was tested. Viewing the restricted aim (dose-range finding study) and the age of the study, it is not discussed in detail. Ref.: 31 Finally, a so-called \"peri-/postnatal toxicity study\" is provided, in which 20 inseminated female rats were administered Compound N°34054 (Climbazole, purity not","endpoint":"developmental toxicity","ingredient":"Climbazole","loael_value":"","noael_unit":"mg/kg","noael_value":"7.2","page":28,"route":"","species":"rat","study_id":"sccp_o_027_noael_013"}
UnifiedCodex:SCCS_SHADOW:beta.noael_studies developmental toxicity 5 mg/kg/day rat oral 90d developmental toxicity SOURCE_SUBDIR=sccp_o_027; REPORT_TITLE=Opinion on Climbazole COLIPA n° P64; OPINION_NUMBER=SCCP/0918/05; COMMITTEE=SCCP; REPORT_DATE=20 September 2005; VALUE_TEXT=5; DOSE=Nevertheless, based on the available information, a cautious NOEL-value of 5 mg/kg/day can be deduced from the 90d oral study with the rat.; EFFECT=te were measured in blood plasma and urine. Therefore, the absorption value for the calculation of the MoS for Climbazole will be considered 100% until sound dermal absorption data are provided. 9. With regard to long term toxicity studies : The dossier clearly suffers from the age of the studies. Nearly all of them have been performed between 1975 and 1983, before GLP-regulations were in place. The descriptions are brief and the raw data are incomplete. Nevertheless, based on the available information, a cautious NOEL-value of 5 mg/kg/day can be deduced from the 90d oral study with the rat. Chronic and carcinogenicity studies are not available. 10. With regard to the teratogenic effects of the substance, a relatively recent study (2001) provides a NOAEL (embryotoxicity) of 30 mg/kg bw/day and a NOAEL (maternal toxicity) of 15 mg/kg bw/day. 11. With regard to the mutagenicity/genotoxicity data The presented tests are old and have not been performed according to recent guidelines. They all show negative results. Due to the lack o; CITATION_NUMBERS=[]; DETAILS_JSON={"cas_number":"38083-17-9","citation":"","dose":"Nevertheless, based on the available information, a cautious NOEL-value of 5 mg/kg/day can be deduced from the 90d oral study with the rat.","duration":"90d","effect":"te were measured in blood plasma and urine. Therefore, the absorption value for the calculation of the MoS for Climbazole will be considered 100% until sound dermal absorption data are provided. 9. With regard to long term toxicity studies : The dossier clearly suffers from the age of the studies. Nearly all of them have been performed between 1975 and 1983, before GLP-regulations were in place. The descriptions are brief and the raw data are incomplete. Nevertheless, based on the available information, a cautious NOEL-value of 5 mg/kg/day can be deduced from the 90d oral study with the rat. Chronic and carcinogenicity studies are not available. 10. With regard to the teratogenic effects of the substance, a relatively recent study (2001) provides a NOAEL (embryotoxicity) of 30 mg/kg bw/day and a NOAEL (maternal toxicity) of 15 mg/kg bw/day. 11. With regard to the mutagenicity/genotoxicity data The presented tests are old and have not been performed according to recent guidelines. They all show negative results. Due to the lack o","endpoint":"developmental toxicity","ingredient":"Climbazole","loael_value":"","noael_unit":"mg/kg/day","noael_value":"5","page":33,"route":"oral","species":"rat","study_id":"sccp_o_027_noael_014"}
UnifiedCodex:SCCS_SHADOW:beta.noael_studies developmental toxicity 30 mg/kg bw/day rat oral 90d developmental toxicity SOURCE_SUBDIR=sccp_o_027; REPORT_TITLE=Opinion on Climbazole COLIPA n° P64; OPINION_NUMBER=SCCP/0918/05; COMMITTEE=SCCP; REPORT_DATE=20 September 2005; VALUE_TEXT=30; DOSE=Nevertheless, based on the available information, a cautious NOEL-value of 5 mg/kg/day can be deduced from the 90d oral study with the rat.; EFFECT=: The dossier clearly suffers from the age of the studies. Nearly all of them have been performed between 1975 and 1983, before GLP-regulations were in place. The descriptions are brief and the raw data are incomplete. Nevertheless, based on the available information, a cautious NOEL-value of 5 mg/kg/day can be deduced from the 90d oral study with the rat. Chronic and carcinogenicity studies are not available. 10. With regard to the teratogenic effects of the substance, a relatively recent study (2001) provides a NOAEL (embryotoxicity) of 30 mg/kg bw/day and a NOAEL (maternal toxicity) of 15 mg/kg bw/day. 11. With regard to the mutagenicity/genotoxicity data The presented tests are old and have not been performed according to recent guidelines. They all show negative results. Due to the lack of carcinogenicity data, however, it is recommended to perform the currently defined basic set of mutagenicity tests. 12. With regard to toxicokinetics: Climbazole appears to be rapidly metabolised into its major metabolite BAY g 6975 throug; CITATION_NUMBERS=[]; DETAILS_JSON={"cas_number":"38083-17-9","citation":"","dose":"Nevertheless, based on the available information, a cautious NOEL-value of 5 mg/kg/day can be deduced from the 90d oral study with the rat.","duration":"90d","effect":": The dossier clearly suffers from the age of the studies. Nearly all of them have been performed between 1975 and 1983, before GLP-regulations were in place. The descriptions are brief and the raw data are incomplete. Nevertheless, based on the available information, a cautious NOEL-value of 5 mg/kg/day can be deduced from the 90d oral study with the rat. Chronic and carcinogenicity studies are not available. 10. With regard to the teratogenic effects of the substance, a relatively recent study (2001) provides a NOAEL (embryotoxicity) of 30 mg/kg bw/day and a NOAEL (maternal toxicity) of 15 mg/kg bw/day. 11. With regard to the mutagenicity/genotoxicity data The presented tests are old and have not been performed according to recent guidelines. They all show negative results. Due to the lack of carcinogenicity data, however, it is recommended to perform the currently defined basic set of mutagenicity tests. 12. With regard to toxicokinetics: Climbazole appears to be rapidly metabolised into its major metabolite BAY g 6975 throug","endpoint":"developmental toxicity","ingredient":"Climbazole","loael_value":"","noael_unit":"mg/kg bw/day","noael_value":"30","page":33,"route":"oral","species":"rat","study_id":"sccp_o_027_noael_015"}
UnifiedCodex:SCCS_SHADOW:beta.noael_studies developmental toxicity 30 mg/kg bw/day rat oral 90d developmental toxicity SOURCE_SUBDIR=sccp_o_027; REPORT_TITLE=Opinion on Climbazole COLIPA n° P64; OPINION_NUMBER=SCCP/0918/05; COMMITTEE=SCCP; REPORT_DATE=20 September 2005; VALUE_TEXT=30; DOSE=Nevertheless, based on the available information, a cautious NOEL-value of 5 mg/kg/day can be deduced from the 90d oral study with the rat.; EFFECT=he studies. Nearly all of them have been performed between 1975 and 1983, before GLP-regulations were in place. The descriptions are brief and the raw data are incomplete. Nevertheless, based on the available information, a cautious NOEL-value of 5 mg/kg/day can be deduced from the 90d oral study with the rat. Chronic and carcinogenicity studies are not available. 10. With regard to the teratogenic effects of the substance, a relatively recent study (2001) provides a NOAEL (embryotoxicity) of 30 mg/kg bw/day and a NOAEL (maternal toxicity) of 15 mg/kg bw/day. 11. With regard to the mutagenicity/genotoxicity data The presented tests are old and have not been performed according to recent guidelines. They all show negative results. Due to the lack of carcinogenicity data, however, it is recommended to perform the currently defined basic set of mutagenicity tests. 12. With regard to toxicokinetics: Climbazole appears to be rapidly metabolised into its major metabolite BAY g 6975 through first pass metabolism. Excretion mainly occurs; CITATION_NUMBERS=[]; DETAILS_JSON={"cas_number":"38083-17-9","citation":"","dose":"Nevertheless, based on the available information, a cautious NOEL-value of 5 mg/kg/day can be deduced from the 90d oral study with the rat.","duration":"90d","effect":"he studies. Nearly all of them have been performed between 1975 and 1983, before GLP-regulations were in place. The descriptions are brief and the raw data are incomplete. Nevertheless, based on the available information, a cautious NOEL-value of 5 mg/kg/day can be deduced from the 90d oral study with the rat. Chronic and carcinogenicity studies are not available. 10. With regard to the teratogenic effects of the substance, a relatively recent study (2001) provides a NOAEL (embryotoxicity) of 30 mg/kg bw/day and a NOAEL (maternal toxicity) of 15 mg/kg bw/day. 11. With regard to the mutagenicity/genotoxicity data The presented tests are old and have not been performed according to recent guidelines. They all show negative results. Due to the lack of carcinogenicity data, however, it is recommended to perform the currently defined basic set of mutagenicity tests. 12. With regard to toxicokinetics: Climbazole appears to be rapidly metabolised into its major metabolite BAY g 6975 through first pass metabolism. Excretion mainly occurs","endpoint":"developmental toxicity","ingredient":"Climbazole","loael_value":"","noael_unit":"mg/kg bw/day","noael_value":"30","page":33,"route":"oral","species":"rat","study_id":"sccp_o_027_noael_016"}
UnifiedCodex:SCCS_SHADOW:beta.noael_studies repeated dose toxicity 50 mg/kg bw/day rat oral sub-chronic repeated dose toxicity SOURCE_SUBDIR=sccp_o_027; REPORT_TITLE=Opinion on Climbazole COLIPA n° P64; OPINION_NUMBER=SCCP/0918/05; COMMITTEE=SCCP; REPORT_DATE=20 September 2005; VALUE_TEXT=50; DOSE=The study is acceptable as a dose-finding (pilot) experiment.; EFFECT=SCCP/0918/05 Opinion on Climbazole (P64) 15 Conclusion The study was neither conducted in full compliance with the respective current OECD Guideline, nor has formal adherence to GLP principles been documented and reported. However, due to the availability of detailed information on the study design and findings (including some individual animal data), limited validity in terms of scientific criteria can be assigned. The study is acceptable as a dose-finding (pilot) experiment. Its results indicate that the NOAEL for Climbazole following repeated (sub-chronic) daily per oral dosing in the rat is lower than 50 mg/kg bw/day. The observed adverse effects were blood biochemical changes and morphological organ damage in the liver. Ref.: 30 42-day oral toxicity study with the dog Guideline: 42-day oral toxicity test (1974) according to guidelines at the time Species/strain: Beagle dog Group size: 2 males + 2 females Test substance: BAY e 6975 (Climbazole, purity not stated) Batch no.: 483751 Dose levels: 0, 100 mg/kg bw/day we; CITATION=Ref.: 30 42-day oral toxicity study with the dog Guideline: 42-day oral toxicity test (1974) according to guidelines at the time Species/strain: Beagle dog Group size: 2 males + 2 female; CITATION_NUMBERS=[30,42,1974,2]; REFERENCE=Ref.: 30 42-day oral toxicity study with the dog Guideline: 42-day oral toxicity test (1974) according to guidelines at the time Species/strain: Beagle dog Group size: 2 males + 2 female; DETAILS_JSON={"cas_number":"38083-17-9","citation":"Ref.: 30 42-day oral toxicity study with the dog Guideline: 42-day oral toxicity test (1974) according to guidelines at the time Species/strain: Beagle dog Group size: 2 males + 2 female","dose":"The study is acceptable as a dose-finding (pilot) experiment.","duration":"sub-chronic","effect":"SCCP/0918/05 Opinion on Climbazole (P64) 15 Conclusion The study was neither conducted in full compliance with the respective current OECD Guideline, nor has formal adherence to GLP principles been documented and reported. However, due to the availability of detailed information on the study design and findings (including some individual animal data), limited validity in terms of scientific criteria can be assigned. The study is acceptable as a dose-finding (pilot) experiment. Its results indicate that the NOAEL for Climbazole following repeated (sub-chronic) daily per oral dosing in the rat is lower than 50 mg/kg bw/day. The observed adverse effects were blood biochemical changes and morphological organ damage in the liver. Ref.: 30 42-day oral toxicity study with the dog Guideline: 42-day oral toxicity test (1974) according to guidelines at the time Species/strain: Beagle dog Group size: 2 males + 2 females Test substance: BAY e 6975 (Climbazole, purity not stated) Batch no.: 483751 Dose levels: 0, 100 mg/kg bw/day we","endpoint":"repeated dose toxicity","ingredient":"Climbazole","loael_value":"","noael_unit":"mg/kg bw/day","noael_value":"50","page":15,"route":"oral","species":"rat","study_id":"sccp_o_027_noael_001"}
UnifiedCodex:SCCS_SHADOW:beta.noael_studies repeated dose toxicity 50 mg/kg bw/day - oral sub-chronic repeated dose toxicity SOURCE_SUBDIR=sccp_o_027; REPORT_TITLE=Opinion on Climbazole COLIPA n° P64; OPINION_NUMBER=SCCP/0918/05; COMMITTEE=SCCP; REPORT_DATE=20 September 2005; VALUE_TEXT=50; DOSE=The study results indicate that the NOAEL for Climbazole following repeated (sub-chronic) daily per oral dosing is probably lower than 50 mg/kg bw/day.; EFFECT=gation were affected, and no substance-related macroscopic and microscopic alterations have been observed. Conclusion The study was neither conducted in full compliance with the respective current OECD Guideline, nor has formal adherence to GLP principles been documented and reported. However, due to the availability of detailed information on the study design and findings (including some individual animal data), limited validity in terms of scientific criteria can be assigned. The study results indicate that the NOAEL for Climbazole following repeated (sub-chronic) daily per oral dosing is probably lower than 50 mg/kg bw/day. The observed adverse effects were some clinical findings and blood biochemical/haematological changes.; CITATION_NUMBERS=[]; DETAILS_JSON={"cas_number":"38083-17-9","citation":"","dose":"The study results indicate that the NOAEL for Climbazole following repeated (sub-chronic) daily per oral dosing is probably lower than 50 mg/kg bw/day.","duration":"sub-chronic","effect":"gation were affected, and no substance-related macroscopic and microscopic alterations have been observed. Conclusion The study was neither conducted in full compliance with the respective current OECD Guideline, nor has formal adherence to GLP principles been documented and reported. However, due to the availability of detailed information on the study design and findings (including some individual animal data), limited validity in terms of scientific criteria can be assigned. The study results indicate that the NOAEL for Climbazole following repeated (sub-chronic) daily per oral dosing is probably lower than 50 mg/kg bw/day. The observed adverse effects were some clinical findings and blood biochemical/haematological changes.","endpoint":"repeated dose toxicity","ingredient":"Climbazole","loael_value":"","noael_unit":"mg/kg bw/day","noael_value":"50","page":15,"route":"oral","species":"","study_id":"sccp_o_027_noael_002"}
UnifiedCodex:SCCS_SHADOW:beta.noael_studies repeated dose toxicity 20 mg/kg bw/day dog - sub-chronic repeated dose toxicity SOURCE_SUBDIR=sccp_o_027; REPORT_TITLE=Opinion on Climbazole COLIPA n° P64; OPINION_NUMBER=SCCP/0918/05; COMMITTEE=SCCP; REPORT_DATE=20 September 2005; VALUE_TEXT=20; DOSE=Based on the reported study results, the laboratory proposes to use the highest tested dose of 20 mg/kg bw/day as the NOAEL in this sub-chronic peroral toxicity study in dogs.; EFFECT=Conclusion The study was neither conducted in full compliance with the respective current OECD Guideline, nor has formal adherence to GLP principles been documented and reported. However, due to the availability of detailed information on the study design and findings (including some individual animal data), satisfactory validity in terms of scientific criteria can be assigned to this experiment. Based on the reported study results, the laboratory proposes to use the highest tested dose of 20 mg/kg bw/day as the NOAEL in this sub-chronic peroral toxicity study in dogs. The only test substance-related effects observed exclusively in the high dose group were not considered as adverse effects but rather as signs of adaptive changes indicating increased metabolic activity. Viewing the absence of the full raw data package, it appears to be safer to take into account the NOEL value of 10 mg/kg bw/day. Ref.: 3 3.3.5.3. Chronic (> 12 months) toxicity No chronic toxicity studies have been conducted with Climbazole. 3.3.6. Mutagenicit; CITATION=Ref.: 3 3; CITATION_NUMBERS=[3]; REFERENCE=Ref.: 3 3; DETAILS_JSON={"cas_number":"38083-17-9","citation":"Ref.: 3 3","dose":"Based on the reported study results, the laboratory proposes to use the highest tested dose of 20 mg/kg bw/day as the NOAEL in this sub-chronic peroral toxicity study in dogs.","duration":"sub-chronic","effect":"Conclusion The study was neither conducted in full compliance with the respective current OECD Guideline, nor has formal adherence to GLP principles been documented and reported. However, due to the availability of detailed information on the study design and findings (including some individual animal data), satisfactory validity in terms of scientific criteria can be assigned to this experiment. Based on the reported study results, the laboratory proposes to use the highest tested dose of 20 mg/kg bw/day as the NOAEL in this sub-chronic peroral toxicity study in dogs. The only test substance-related effects observed exclusively in the high dose group were not considered as adverse effects but rather as signs of adaptive changes indicating increased metabolic activity. Viewing the absence of the full raw data package, it appears to be safer to take into account the NOEL value of 10 mg/kg bw/day. Ref.: 3 3.3.5.3. Chronic (> 12 months) toxicity No chronic toxicity studies have been conducted with Climbazole. 3.3.6. Mutagenicit","endpoint":"repeated dose toxicity","ingredient":"Climbazole","loael_value":"","noael_unit":"mg/kg bw/day","noael_value":"20","page":18,"route":"","species":"dog","study_id":"sccp_o_027_noael_005"}
UnifiedCodex:SCCS_SHADOW:beta.noael_studies repeated dose toxicity 10 mg/kg bw/day dog - sub-chronic repeated dose toxicity SOURCE_SUBDIR=sccp_o_027; REPORT_TITLE=Opinion on Climbazole COLIPA n° P64; OPINION_NUMBER=SCCP/0918/05; COMMITTEE=SCCP; REPORT_DATE=20 September 2005; VALUE_TEXT=10; DOSE=Based on the reported study results, the laboratory proposes to use the highest tested dose of 20 mg/kg bw/day as the NOAEL in this sub-chronic peroral toxicity study in dogs.; EFFECT=teria can be assigned to this experiment. Based on the reported study results, the laboratory proposes to use the highest tested dose of 20 mg/kg bw/day as the NOAEL in this sub-chronic peroral toxicity study in dogs. The only test substance-related effects observed exclusively in the high dose group were not considered as adverse effects but rather as signs of adaptive changes indicating increased metabolic activity. Viewing the absence of the full raw data package, it appears to be safer to take into account the NOEL value of 10 mg/kg bw/day. Ref.: 3 3.3.5.3. Chronic (> 12 months) toxicity No chronic toxicity studies have been conducted with Climbazole. 3.3.6. Mutagenicity / Genotoxicity 3.3.6.1. Mutagenicity / Genotoxicity in vitro Ames test 1 (parent compound) Guideline: Ames test (1977) according to guidelines at the time Species/strain: Salmonella typhimurium, TA100, TA1537, TA98 Replicates: 2 Test substance: BAY e 6975 (Climbazole, purity not stated) Batch no.: 323568 Concentrations: 0, 3.15, 10, 31.5, 100, 315, 100; CITATION=Ref.: 3 3; CITATION_NUMBERS=[3]; REFERENCE=Ref.: 3 3; DETAILS_JSON={"cas_number":"38083-17-9","citation":"Ref.: 3 3","dose":"Based on the reported study results, the laboratory proposes to use the highest tested dose of 20 mg/kg bw/day as the NOAEL in this sub-chronic peroral toxicity study in dogs.","duration":"sub-chronic","effect":"teria can be assigned to this experiment. Based on the reported study results, the laboratory proposes to use the highest tested dose of 20 mg/kg bw/day as the NOAEL in this sub-chronic peroral toxicity study in dogs. The only test substance-related effects observed exclusively in the high dose group were not considered as adverse effects but rather as signs of adaptive changes indicating increased metabolic activity. Viewing the absence of the full raw data package, it appears to be safer to take into account the NOEL value of 10 mg/kg bw/day. Ref.: 3 3.3.5.3. Chronic (> 12 months) toxicity No chronic toxicity studies have been conducted with Climbazole. 3.3.6. Mutagenicity / Genotoxicity 3.3.6.1. Mutagenicity / Genotoxicity in vitro Ames test 1 (parent compound) Guideline: Ames test (1977) according to guidelines at the time Species/strain: Salmonella typhimurium, TA100, TA1537, TA98 Replicates: 2 Test substance: BAY e 6975 (Climbazole, purity not stated) Batch no.: 323568 Concentrations: 0, 3.15, 10, 31.5, 100, 315, 100","endpoint":"repeated dose toxicity","ingredient":"Climbazole","loael_value":"","noael_unit":"mg/kg bw/day","noael_value":"10","page":18,"route":"","species":"dog","study_id":"sccp_o_027_noael_006"}
UnifiedCodex:SCCS_SHADOW:beta.noael_studies repeated dose toxicity 5 mg/kg bw/day rat oral subacute repeated dose toxicity SOURCE_SUBDIR=sccp_o_164; REPORT_TITLE=OPINION ON Climbazole COLIPA n° P64; OPINION_NUMBER=SCCP/1204/08; COMMITTEE=Scientific Committee on Consumer Products (SCCP); REPORT_DATE=21 January 2009; VALUE_TEXT=5; DOSE=For ethical reasons and after a thorough re-examination of the available information, the SCCP proposed to accept the use of a cautious NOEL-value of 5 mg/kg bw/day, deduced from the 90d oral study with the rat.; EFFECT=ission contained subacute oral studies with rats and dogs, a subacute dermal toxicity study with the rabbit and subchronic oral studies with rats and dogs. The main problem was that the dossier suffered from the age of the studies. Nearly all of them were performed between 1975 and 1983, before GLP-regulations were in place. The descriptions were brief and the raw data incomplete. For ethical reasons and after a thorough re-examination of the available information, the SCCP proposed to accept the use of a cautious NOEL-value of 5 mg/kg bw/day, deduced from the 90d oral study with the rat.; CITATION_NUMBERS=[]; DETAILS_JSON={"cas_number":"38083-17-9","citation":"","dose":"For ethical reasons and after a thorough re-examination of the available information, the SCCP proposed to accept the use of a cautious NOEL-value of 5 mg/kg bw/day, deduced from the 90d oral study with the rat.","duration":"subacute","effect":"ission contained subacute oral studies with rats and dogs, a subacute dermal toxicity study with the rabbit and subchronic oral studies with rats and dogs. The main problem was that the dossier suffered from the age of the studies. Nearly all of them were performed between 1975 and 1983, before GLP-regulations were in place. The descriptions were brief and the raw data incomplete. For ethical reasons and after a thorough re-examination of the available information, the SCCP proposed to accept the use of a cautious NOEL-value of 5 mg/kg bw/day, deduced from the 90d oral study with the rat.","endpoint":"repeated dose toxicity","ingredient":"1-(4-chlorophenoxy)-1-imidazol-1-yl-3,3-dimethyl-2","loael_value":"","noael_unit":"mg/kg bw/day","noael_value":"5","page":16,"route":"oral","species":"rat","study_id":"sccp_o_164_noael_001"}
UnifiedCodex:SCCS_SHADOW:beta.noael_studies repeated dose toxicity 5 mg/kg bw/day rat dermal subacute repeated dose toxicity SOURCE_SUBDIR=sccp_o_164; REPORT_TITLE=OPINION ON Climbazole COLIPA n° P64; OPINION_NUMBER=SCCP/1204/08; COMMITTEE=Scientific Committee on Consumer Products (SCCP); REPORT_DATE=21 January 2009; VALUE_TEXT=5; DOSE=Based upon the available test descriptions and raw data, the SCCP deduced a conservative NOEL value of 5 mg/kg bw/day from the presented 90-day study with the rat.; EFFECT=mbazole concentration of 0.5% is concerned, a recent in vitro dermal absorption study reveals absorption levels of 1.10 µg/cm² (2.23%) and 1.25 µg/cm² (3.46%) for an aqueous hair lotion and a water-in- oil skin preparation, respectively. General toxicity As already stated in SCCP/0981/05, several subacute and subchronic studies with rodents and non-rodents were available, though were performed before the introduction of GLP. Based upon the available test descriptions and raw data, the SCCP deduced a conservative NOEL value of 5 mg/kg bw/day from the presented 90-day study with the rat. Mutagenicity / genotoxicity The recent submission contains a full mutagenicity/genotoxicity dossier as requested by the SCCP. Climbazole showed to be negative in the Ames test, in the in vitro micronucleus test and in the in vitro mammalian cell gene mutation test (with the exception of the prolonged exposure scheme, where some mutagenic potential was apparent). The in vivo micronucleus test and the in vivo UDS assay with Climbazole showed the; CITATION_NUMBERS=[]; DETAILS_JSON={"cas_number":"38083-17-9","citation":"","dose":"Based upon the available test descriptions and raw data, the SCCP deduced a conservative NOEL value of 5 mg/kg bw/day from the presented 90-day study with the rat.","duration":"subacute","effect":"mbazole concentration of 0.5% is concerned, a recent in vitro dermal absorption study reveals absorption levels of 1.10 µg/cm² (2.23%) and 1.25 µg/cm² (3.46%) for an aqueous hair lotion and a water-in- oil skin preparation, respectively. General toxicity As already stated in SCCP/0981/05, several subacute and subchronic studies with rodents and non-rodents were available, though were performed before the introduction of GLP. Based upon the available test descriptions and raw data, the SCCP deduced a conservative NOEL value of 5 mg/kg bw/day from the presented 90-day study with the rat. Mutagenicity / genotoxicity The recent submission contains a full mutagenicity/genotoxicity dossier as requested by the SCCP. Climbazole showed to be negative in the Ames test, in the in vitro micronucleus test and in the in vitro mammalian cell gene mutation test (with the exception of the prolonged exposure scheme, where some mutagenic potential was apparent). The in vivo micronucleus test and the in vivo UDS assay with Climbazole showed the","endpoint":"repeated dose toxicity","ingredient":"1-(4-chlorophenoxy)-1-imidazol-1-yl-3,3-dimethyl-2","loael_value":"","noael_unit":"mg/kg bw/day","noael_value":"5","page":25,"route":"dermal","species":"rat","study_id":"sccp_o_164_noael_011"}
UnifiedCodex:SCCS_SHADOW:beta.noael_studies repeated dose toxicity 5 mg/kg bw/day rat dermal subacute repeated dose toxicity SOURCE_SUBDIR=sccs_o_120; REPORT_TITLE=ADDENDUM to the Opinion SCCS/1506/13 Climbazole Cosmetics Europe: P64; OPINION_NUMBER=SCCS/1506/13; COMMITTEE=Scientific Committee on Consumer Safety (SCCS); REPORT_DATE=18 June 2013; VALUE_TEXT=5; DOSE=Based upon the available test descriptions and raw data, the SCCP deduced a conservative NOEL value of 5 mg/kg bw/day from the presented 90-day study with the rat.; EFFECT=under leave-on conditions and a Climbazole concentration of 0.5% is concerned, a recent in vitro dermal absorption study reveals absorption levels of 1.10 μg/cm² (2.23%) and 1.25 μg/cm² (3.46%) for an aqueous hair lotion and a water- in-oil skin preparation, respectively. General toxicity Several subacute and subchronic studies with rodents and non-rodents were available, though were performed before the introduction of GLP. Based upon the available test descriptions and raw data, the SCCP deduced a conservative NOEL value of 5 mg/kg bw/day from the presented 90-day study with the rat. Mutagenicity / genotoxicity Climbazole showed to be negative in the Ames test, in the in vitro micronucleus test and in the in vitro mammalian cell gene mutation test (with the exception of the prolonged exposure scheme, where some mutagenic potential was apparent). The in vivo micronucleus test and the in vivo UDS assay with Climbazole showed the substance to be negative, meaning that no mutagenic/genotoxic effects are to be expected. Reprodu; CITATION_NUMBERS=[]; DETAILS_JSON={"cas_number":"38083-17-9","citation":"","dose":"Based upon the available test descriptions and raw data, the SCCP deduced a conservative NOEL value of 5 mg/kg bw/day from the presented 90-day study with the rat.","duration":"subacute","effect":"under leave-on conditions and a Climbazole concentration of 0.5% is concerned, a recent in vitro dermal absorption study reveals absorption levels of 1.10 μg/cm² (2.23%) and 1.25 μg/cm² (3.46%) for an aqueous hair lotion and a water- in-oil skin preparation, respectively. General toxicity Several subacute and subchronic studies with rodents and non-rodents were available, though were performed before the introduction of GLP. Based upon the available test descriptions and raw data, the SCCP deduced a conservative NOEL value of 5 mg/kg bw/day from the presented 90-day study with the rat. Mutagenicity / genotoxicity Climbazole showed to be negative in the Ames test, in the in vitro micronucleus test and in the in vitro mammalian cell gene mutation test (with the exception of the prolonged exposure scheme, where some mutagenic potential was apparent). The in vivo micronucleus test and the in vivo UDS assay with Climbazole showed the substance to be negative, meaning that no mutagenic/genotoxic effects are to be expected. Reprodu","endpoint":"repeated dose toxicity","ingredient":"1-(4-chlorophenoxy)-1-imidazol-1-yl-3,3-dimethyl-2","loael_value":"","noael_unit":"mg/kg bw/day","noael_value":"5","page":6,"route":"dermal","species":"rat","study_id":"sccs_o_120_noael_001"}
UnifiedCodex:SCCS_SHADOW:beta.noael_studies reproductive toxicity 30 mg/kg bw/day rat - - reproductive toxicity SOURCE_SUBDIR=sccp_o_164; REPORT_TITLE=OPINION ON Climbazole COLIPA n° P64; OPINION_NUMBER=SCCP/1204/08; COMMITTEE=Scientific Committee on Consumer Products (SCCP); REPORT_DATE=21 January 2009; VALUE_TEXT=30; DOSE=ative control) in hepatocytes isolated from treated male rats.; EFFECT=ative control) in hepatocytes isolated from treated male rats. Therefore they conclude that Climbazole was found negative in the in vivo UDS test in rats, when tested up to the maximum tolerated dose level. Ref.: 50 3.3.7. Carcinogenicity No data submitted 3.3.8. Reproductive toxicity Taken from SCCP/0981/05: A 1-generation reproduction study was presented, though its relevance was questioned. With regard to the teratogenic effects of the substance, the SCCP opinion mentions a study of 2001 providing a useful NOAEL (embryotoxicity) of 30 mg/kg bw/day and a NOAEL (maternal toxicity) of 15 mg/kg bw/day. 3.3.9. Toxicokinetics Taken from SCCP/0981/05: In vivo metabolic disposition studies in humans, dogs, rats and mice were presented in the previous SCCP submission. They showed that Climbazole appeared to be rapidly metabolised into its major metabolite through first pass metabolism. Excretion mainly occurred through the bile. Again, the presented data package contained old tests, which reduced their scientific validity. The; CITATION=Ref.: 50 3; CITATION_NUMBERS=[50,3]; REFERENCE=Ref.: 50 3; DETAILS_JSON={"cas_number":"38083-17-9","citation":"Ref.: 50 3","dose":"ative control) in hepatocytes isolated from treated male rats.","duration":"","effect":"ative control) in hepatocytes isolated from treated male rats. Therefore they conclude that Climbazole was found negative in the in vivo UDS test in rats, when tested up to the maximum tolerated dose level. Ref.: 50 3.3.7. Carcinogenicity No data submitted 3.3.8. Reproductive toxicity Taken from SCCP/0981/05: A 1-generation reproduction study was presented, though its relevance was questioned. With regard to the teratogenic effects of the substance, the SCCP opinion mentions a study of 2001 providing a useful NOAEL (embryotoxicity) of 30 mg/kg bw/day and a NOAEL (maternal toxicity) of 15 mg/kg bw/day. 3.3.9. Toxicokinetics Taken from SCCP/0981/05: In vivo metabolic disposition studies in humans, dogs, rats and mice were presented in the previous SCCP submission. They showed that Climbazole appeared to be rapidly metabolised into its major metabolite through first pass metabolism. Excretion mainly occurred through the bile. Again, the presented data package contained old tests, which reduced their scientific validity. The","endpoint":"reproductive toxicity","ingredient":"1-(4-chlorophenoxy)-1-imidazol-1-yl-3,3-dimethyl-2","loael_value":"","noael_unit":"mg/kg bw/day","noael_value":"30","page":22,"route":"","species":"rat","study_id":"sccp_o_164_noael_002"}
UnifiedCodex:SCCS_SHADOW:beta.noael_studies reproductive toxicity 30 mg/kg bw/day rat - - reproductive toxicity SOURCE_SUBDIR=sccp_o_164; REPORT_TITLE=OPINION ON Climbazole COLIPA n° P64; OPINION_NUMBER=SCCP/1204/08; COMMITTEE=Scientific Committee on Consumer Products (SCCP); REPORT_DATE=21 January 2009; VALUE_TEXT=30; DOSE=Therefore they conclude that Climbazole was found negative in the in vivo UDS test in rats, when tested up to the maximum tolerated dose level.; EFFECT=ted male rats. Therefore they conclude that Climbazole was found negative in the in vivo UDS test in rats, when tested up to the maximum tolerated dose level. Ref.: 50 3.3.7. Carcinogenicity No data submitted 3.3.8. Reproductive toxicity Taken from SCCP/0981/05: A 1-generation reproduction study was presented, though its relevance was questioned. With regard to the teratogenic effects of the substance, the SCCP opinion mentions a study of 2001 providing a useful NOAEL (embryotoxicity) of 30 mg/kg bw/day and a NOAEL (maternal toxicity) of 15 mg/kg bw/day. 3.3.9. Toxicokinetics Taken from SCCP/0981/05: In vivo metabolic disposition studies in humans, dogs, rats and mice were presented in the previous SCCP submission. They showed that Climbazole appeared to be rapidly metabolised into its major metabolite through first pass metabolism. Excretion mainly occurred through the bile. Again, the presented data package contained old tests, which reduced their scientific validity. The SCCP was of the opinion that, since the mother c; CITATION=Ref.: 50 3; CITATION_NUMBERS=[50,3]; REFERENCE=Ref.: 50 3; DETAILS_JSON={"cas_number":"38083-17-9","citation":"Ref.: 50 3","dose":"Therefore they conclude that Climbazole was found negative in the in vivo UDS test in rats, when tested up to the maximum tolerated dose level.","duration":"","effect":"ted male rats. Therefore they conclude that Climbazole was found negative in the in vivo UDS test in rats, when tested up to the maximum tolerated dose level. Ref.: 50 3.3.7. Carcinogenicity No data submitted 3.3.8. Reproductive toxicity Taken from SCCP/0981/05: A 1-generation reproduction study was presented, though its relevance was questioned. With regard to the teratogenic effects of the substance, the SCCP opinion mentions a study of 2001 providing a useful NOAEL (embryotoxicity) of 30 mg/kg bw/day and a NOAEL (maternal toxicity) of 15 mg/kg bw/day. 3.3.9. Toxicokinetics Taken from SCCP/0981/05: In vivo metabolic disposition studies in humans, dogs, rats and mice were presented in the previous SCCP submission. They showed that Climbazole appeared to be rapidly metabolised into its major metabolite through first pass metabolism. Excretion mainly occurred through the bile. Again, the presented data package contained old tests, which reduced their scientific validity. The SCCP was of the opinion that, since the mother c","endpoint":"reproductive toxicity","ingredient":"1-(4-chlorophenoxy)-1-imidazol-1-yl-3,3-dimethyl-2","loael_value":"","noael_unit":"mg/kg bw/day","noael_value":"30","page":22,"route":"","species":"rat","study_id":"sccp_o_164_noael_003"}
UnifiedCodex:SCCS_SHADOW:beta.noael_studies reproductive toxicity 30 mg/kg bw/day mouse oral - reproductive toxicity SOURCE_SUBDIR=sccp_o_164; REPORT_TITLE=OPINION ON Climbazole COLIPA n° P64; OPINION_NUMBER=SCCP/1204/08; COMMITTEE=Scientific Committee on Consumer Products (SCCP); REPORT_DATE=21 January 2009; VALUE_TEXT=30; DOSE=Reproduction toxicity As mentioned earlier (SCCP/0981/05), Climbazole was tested in a 1-generation reproductive toxicity test which was considered questionable as far as its overall scientific validity is concerned, and in well-performed teratogenicity study, leading to a NOAEL (embryotoxicity) of 30 mg/kg bw/day and a NOAEL (maternal toxicity)...; EFFECT=rolonged exposure scheme, where some mutagenic potential was apparent). The in vivo micronucleus test and the in vivo UDS assay with Climbazole showed the substance to be negative, meaning that no mutagenic/genotoxic effects are to be expected. Reproduction toxicity As mentioned earlier (SCCP/0981/05), Climbazole was tested in a 1-generation reproductive toxicity test which was considered questionable as far as its overall scientific validity is concerned, and in well-performed teratogenicity study, leading to a NOAEL (embryotoxicity) of 30 mg/kg bw/day and a NOAEL (maternal toxicity) of 15 mg/kg bw/day. Toxicokinetics A newly performed oral bioavailability assay of 14C Climbazole in mice confirms the results that were described earlier, namely that Climbazole is rapidly absorbed and excreted and that its maximum concentration in plasma is reached after approximately 8 hours. Calculation of the Margin of Safety Taking into account the mean values measured in the scientifically acceptable in vitro dermal absorption study for; CITATION_NUMBERS=[]; DETAILS_JSON={"cas_number":"38083-17-9","citation":"","dose":"Reproduction toxicity As mentioned earlier (SCCP/0981/05), Climbazole was tested in a 1-generation reproductive toxicity test which was considered questionable as far as its overall scientific validity is concerned, and in well-performed teratogenicity study, leading to a NOAEL (embryotoxicity) of 30 mg/kg bw/day and a NOAEL (maternal toxicity)...","duration":"","effect":"rolonged exposure scheme, where some mutagenic potential was apparent). The in vivo micronucleus test and the in vivo UDS assay with Climbazole showed the substance to be negative, meaning that no mutagenic/genotoxic effects are to be expected. Reproduction toxicity As mentioned earlier (SCCP/0981/05), Climbazole was tested in a 1-generation reproductive toxicity test which was considered questionable as far as its overall scientific validity is concerned, and in well-performed teratogenicity study, leading to a NOAEL (embryotoxicity) of 30 mg/kg bw/day and a NOAEL (maternal toxicity) of 15 mg/kg bw/day. Toxicokinetics A newly performed oral bioavailability assay of 14C Climbazole in mice confirms the results that were described earlier, namely that Climbazole is rapidly absorbed and excreted and that its maximum concentration in plasma is reached after approximately 8 hours. Calculation of the Margin of Safety Taking into account the mean values measured in the scientifically acceptable in vitro dermal absorption study for","endpoint":"reproductive toxicity","ingredient":"1-(4-chlorophenoxy)-1-imidazol-1-yl-3,3-dimethyl-2","loael_value":"","noael_unit":"mg/kg bw/day","noael_value":"30","page":25,"route":"oral","species":"mouse","study_id":"sccp_o_164_noael_012"}
UnifiedCodex:SCCS_SHADOW:beta.noael_studies reproductive toxicity 30 mg/kg bw/day mouse oral - reproductive toxicity SOURCE_SUBDIR=sccp_o_164; REPORT_TITLE=OPINION ON Climbazole COLIPA n° P64; OPINION_NUMBER=SCCP/1204/08; COMMITTEE=Scientific Committee on Consumer Products (SCCP); REPORT_DATE=21 January 2009; VALUE_TEXT=30; DOSE=Reproduction toxicity As mentioned earlier (SCCP/0981/05), Climbazole was tested in a 1-generation reproductive toxicity test which was considered questionable as far as its overall scientific validity is concerned, and in well-performed teratogenicity study, leading to a NOAEL (embryotoxicity) of 30 mg/kg bw/day and a NOAEL (maternal toxicity)...; EFFECT=otential was apparent). The in vivo micronucleus test and the in vivo UDS assay with Climbazole showed the substance to be negative, meaning that no mutagenic/genotoxic effects are to be expected. Reproduction toxicity As mentioned earlier (SCCP/0981/05), Climbazole was tested in a 1-generation reproductive toxicity test which was considered questionable as far as its overall scientific validity is concerned, and in well-performed teratogenicity study, leading to a NOAEL (embryotoxicity) of 30 mg/kg bw/day and a NOAEL (maternal toxicity) of 15 mg/kg bw/day. Toxicokinetics A newly performed oral bioavailability assay of 14C Climbazole in mice confirms the results that were described earlier, namely that Climbazole is rapidly absorbed and excreted and that its maximum concentration in plasma is reached after approximately 8 hours. Calculation of the Margin of Safety Taking into account the mean values measured in the scientifically acceptable in vitro dermal absorption study for the use of Climbazole in a shampoo (rinse-off),; CITATION_NUMBERS=[]; DETAILS_JSON={"cas_number":"38083-17-9","citation":"","dose":"Reproduction toxicity As mentioned earlier (SCCP/0981/05), Climbazole was tested in a 1-generation reproductive toxicity test which was considered questionable as far as its overall scientific validity is concerned, and in well-performed teratogenicity study, leading to a NOAEL (embryotoxicity) of 30 mg/kg bw/day and a NOAEL (maternal toxicity)...","duration":"","effect":"otential was apparent). The in vivo micronucleus test and the in vivo UDS assay with Climbazole showed the substance to be negative, meaning that no mutagenic/genotoxic effects are to be expected. Reproduction toxicity As mentioned earlier (SCCP/0981/05), Climbazole was tested in a 1-generation reproductive toxicity test which was considered questionable as far as its overall scientific validity is concerned, and in well-performed teratogenicity study, leading to a NOAEL (embryotoxicity) of 30 mg/kg bw/day and a NOAEL (maternal toxicity) of 15 mg/kg bw/day. Toxicokinetics A newly performed oral bioavailability assay of 14C Climbazole in mice confirms the results that were described earlier, namely that Climbazole is rapidly absorbed and excreted and that its maximum concentration in plasma is reached after approximately 8 hours. Calculation of the Margin of Safety Taking into account the mean values measured in the scientifically acceptable in vitro dermal absorption study for the use of Climbazole in a shampoo (rinse-off),","endpoint":"reproductive toxicity","ingredient":"1-(4-chlorophenoxy)-1-imidazol-1-yl-3,3-dimethyl-2","loael_value":"","noael_unit":"mg/kg bw/day","noael_value":"30","page":25,"route":"oral","species":"mouse","study_id":"sccp_o_164_noael_013"}
UnifiedCodex:SCCS_SHADOW:beta.noael_studies reproductive toxicity 30 mg/kg bw/day mouse oral - reproductive toxicity SOURCE_SUBDIR=sccs_o_120; REPORT_TITLE=ADDENDUM to the Opinion SCCS/1506/13 Climbazole Cosmetics Europe: P64; OPINION_NUMBER=SCCS/1506/13; COMMITTEE=Scientific Committee on Consumer Safety (SCCS); REPORT_DATE=18 June 2013; VALUE_TEXT=30; DOSE=Reproduction toxicity Climbazole was tested in a 1-generation reproductive toxicity test which was considered questionable as far as its overall scientific validity is concerned, and in well-performed teratogenicity study, leading to a NOAEL (embryotoxicity) of 30 mg/kg bw/day and a NOAEL (maternal toxicity) of 15 mg/kg bw/day.; EFFECT=tion test (with the exception of the prolonged exposure scheme, where some mutagenic potential was apparent). The in vivo micronucleus test and the in vivo UDS assay with Climbazole showed the substance to be negative, meaning that no mutagenic/genotoxic effects are to be expected. Reproduction toxicity Climbazole was tested in a 1-generation reproductive toxicity test which was considered questionable as far as its overall scientific validity is concerned, and in well-performed teratogenicity study, leading to a NOAEL (embryotoxicity) of 30 mg/kg bw/day and a NOAEL (maternal toxicity) of 15 mg/kg bw/day. Toxicokinetics A newly performed oral bioavailability assay of 14C Climbazole in mice confirms the results that were described earlier, namely that Climbazole is rapidly absorbed and excreted and that its maximum concentration in plasma is reached after approximately 8 hours.; CITATION_NUMBERS=[]; DETAILS_JSON={"cas_number":"38083-17-9","citation":"","dose":"Reproduction toxicity Climbazole was tested in a 1-generation reproductive toxicity test which was considered questionable as far as its overall scientific validity is concerned, and in well-performed teratogenicity study, leading to a NOAEL (embryotoxicity) of 30 mg/kg bw/day and a NOAEL (maternal toxicity) of 15 mg/kg bw/day.","duration":"","effect":"tion test (with the exception of the prolonged exposure scheme, where some mutagenic potential was apparent). The in vivo micronucleus test and the in vivo UDS assay with Climbazole showed the substance to be negative, meaning that no mutagenic/genotoxic effects are to be expected. Reproduction toxicity Climbazole was tested in a 1-generation reproductive toxicity test which was considered questionable as far as its overall scientific validity is concerned, and in well-performed teratogenicity study, leading to a NOAEL (embryotoxicity) of 30 mg/kg bw/day and a NOAEL (maternal toxicity) of 15 mg/kg bw/day. Toxicokinetics A newly performed oral bioavailability assay of 14C Climbazole in mice confirms the results that were described earlier, namely that Climbazole is rapidly absorbed and excreted and that its maximum concentration in plasma is reached after approximately 8 hours.","endpoint":"reproductive toxicity","ingredient":"1-(4-chlorophenoxy)-1-imidazol-1-yl-3,3-dimethyl-2","loael_value":"","noael_unit":"mg/kg bw/day","noael_value":"30","page":6,"route":"oral","species":"mouse","study_id":"sccs_o_120_noael_002"}
UnifiedCodex:SCCS_SHADOW:beta.noael_studies reproductive toxicity 30 mg/kg bw/day mouse oral - reproductive toxicity SOURCE_SUBDIR=sccs_o_120; REPORT_TITLE=ADDENDUM to the Opinion SCCS/1506/13 Climbazole Cosmetics Europe: P64; OPINION_NUMBER=SCCS/1506/13; COMMITTEE=Scientific Committee on Consumer Safety (SCCS); REPORT_DATE=18 June 2013; VALUE_TEXT=30; DOSE=Reproduction toxicity Climbazole was tested in a 1-generation reproductive toxicity test which was considered questionable as far as its overall scientific validity is concerned, and in well-performed teratogenicity study, leading to a NOAEL (embryotoxicity) of 30 mg/kg bw/day and a NOAEL (maternal toxicity) of 15 mg/kg bw/day.; EFFECT=xposure scheme, where some mutagenic potential was apparent). The in vivo micronucleus test and the in vivo UDS assay with Climbazole showed the substance to be negative, meaning that no mutagenic/genotoxic effects are to be expected. Reproduction toxicity Climbazole was tested in a 1-generation reproductive toxicity test which was considered questionable as far as its overall scientific validity is concerned, and in well-performed teratogenicity study, leading to a NOAEL (embryotoxicity) of 30 mg/kg bw/day and a NOAEL (maternal toxicity) of 15 mg/kg bw/day. Toxicokinetics A newly performed oral bioavailability assay of 14C Climbazole in mice confirms the results that were described earlier, namely that Climbazole is rapidly absorbed and excreted and that its maximum concentration in plasma is reached after approximately 8 hours.; CITATION_NUMBERS=[]; DETAILS_JSON={"cas_number":"38083-17-9","citation":"","dose":"Reproduction toxicity Climbazole was tested in a 1-generation reproductive toxicity test which was considered questionable as far as its overall scientific validity is concerned, and in well-performed teratogenicity study, leading to a NOAEL (embryotoxicity) of 30 mg/kg bw/day and a NOAEL (maternal toxicity) of 15 mg/kg bw/day.","duration":"","effect":"xposure scheme, where some mutagenic potential was apparent). The in vivo micronucleus test and the in vivo UDS assay with Climbazole showed the substance to be negative, meaning that no mutagenic/genotoxic effects are to be expected. Reproduction toxicity Climbazole was tested in a 1-generation reproductive toxicity test which was considered questionable as far as its overall scientific validity is concerned, and in well-performed teratogenicity study, leading to a NOAEL (embryotoxicity) of 30 mg/kg bw/day and a NOAEL (maternal toxicity) of 15 mg/kg bw/day. Toxicokinetics A newly performed oral bioavailability assay of 14C Climbazole in mice confirms the results that were described earlier, namely that Climbazole is rapidly absorbed and excreted and that its maximum concentration in plasma is reached after approximately 8 hours.","endpoint":"reproductive toxicity","ingredient":"1-(4-chlorophenoxy)-1-imidazol-1-yl-3,3-dimethyl-2","loael_value":"","noael_unit":"mg/kg bw/day","noael_value":"30","page":6,"route":"oral","species":"mouse","study_id":"sccs_o_120_noael_003"}
openFDA substances 4 endpoints
Source Endpoint Type Value Unit Species Route Duration Study Type Reference
openFDA substances FDA UNII substance identifier 9N42CW7I54 UNII - - - chemical {"approval_status":null,"molecular_formula":"C15H17ClN2O2","source_table":"substance_identifiers_fda","substance_class":"chemical","unii_code":"9N42CW7I54"}
openFDA substances FDA UNII substance identifier 9N42CW7I54 UNII - - - chemical {"approval_status":null,"molecular_formula":"C15H17ClN2O2","source_table":"substance_identifiers_fda","substance_class":"chemical","unii_code":"9N42CW7I54"}
openFDA substances FDA UNII substance identifier 9N42CW7I54 UNII - - - chemical {"approval_status":null,"molecular_formula":"C15H17ClN2O2","source_table":"substance_identifiers_fda","substance_class":"chemical","unii_code":"9N42CW7I54"}
openFDA substances FDA UNII substance identifier 9N42CW7I54 UNII - - - chemical {"approval_status":null,"molecular_formula":"C15H17ClN2O2","source_table":"substance_identifiers_fda","substance_class":"chemical","unii_code":"9N42CW7I54"}