46779203.der.pdf

• filename: 46779203.der.pdf
• MRIDs: 46779203
• CHEMICAL_SUBSTANCE_NAME: Methimazole
• CHEMICAL_CASRN: 60-56-0
• CHEMICAL_PC_CODE: 600093
• STUDY_CITATION: Schaefer, GJ (2006) Validation of Developmental Neurotoxicity Endpoints in Rats Administered Methimazole in Drinking Water. WIL Research Laboratories, Inc. WIL-99199, March 7, 2006. MRID 46779203. Unpublished.
• STUDY_YEAR: 2006.0
• EXECUTIVE_SUMMARY: Methimazole: In a positive control developmental neurotoxicity study (MRID 446779203) Methimazole (purity and lot # not provided) was administered to pregnant female Sprague-Dawley rats (#/dose not provided) in the drinking water at concentrations of 0, 10, 30, or 100 ppm from gestation day (GD) 6 through postnatal day (PND) 21. The report stated that body weights, food and water consumption, and a modified functional observational battery (mFOB) were evaluated in the dams. Brain weights, qualitative neuropathology and quantitative brain morphometry were evaluated in the pups at PND 11, 22 and 72. Pups were also evaluated for auditory startle, locomotor activity, learning and memory (Biel Maze) and mFOB several times. Details on these evaluation methods were not provided. The investigators concluded that: ¿ Based on the endpoints affected (e.g., pup body weight, locomotor activity, auditory startle response, learning and memory, brain weight and length, qualitative and quantitative neuropathology), Methimazole altered multiple functional domains in the F1 generation demonstrating that this compound is acceptable for use as a positive control agent in DNT studies. ¿ Both immersion and perfusion fixation of the PND 11 pup brains provided adequate tissue samples for quantitative morphometrics and qualitative histopathology. This study is classified Unacceptable/Nonguideline. The reviewer can not determine whether WIL Research Laboratory can detect the effects discussed in the investigators¿ conclusions since there were no details regarding the methods, test animal, test material, individual animal data or summary data (other than several graphs). Based on the parameters in the graphs and those mentioned in the report¿s results section it appears that this study may be acceptable as positive control data if a complete report is submitted.
• STUDY_TYPE: Developmental-Neurotoxicity
• GUIDELINE_COMMENT: NA [870.6300, Developmental neurotoxicity study]
• ADMIN_ROUTE: Oral
• DOSE_PERIOD: Treatment Range: 6 to 21 Gestation Days; Positive Control Study
• txr: 54597.0
• memoDate: 2012-03-20
• UpdateDate: 2017-11-17
• Comments:

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