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8728368 
Technical Report 
Twenty-eight-day repeated-dose oral toxicity study of T-7701 in rats 
Chemicals Evaluation and Research Institute, Japan :: CERI 
2002 
Sumitomo 3M Limited 
Japan 
3M-MPCA-00215660; B11-0691 
English 
A 28-day repeated dose toxicity study of orally administered T-7701 followed by a 14-day recovery period was performed in groups of 6 male and 6 female Crj: CD (SD) IGS rats at 5 weeks of age. Four dose levels were selected with the highest dose of 320 mg/kg/day, and 80, 20 and 5 mg/kg/day. Recovery groups were prepared for the 320 mg/kg and vehicle control groups. No deaths were observed throughout the study. No abnormalities were noted in body weights and food intakes during the dosing period, and hematological examinations and urinalyses at the termination of the dosing period. In clinical signs during the dosing period, decreased spontaneous locomotion was observed in the 320 mg/kg males and females. In blood chemical examinations at the termination of the dosing period, increased GPT, albumin and A/G ratio were noted in the 320 mg/kg males. In organ weights at the termination of the dosing period, increased absolute and relative liver weights were noted in the 80 and 320 mg/kg males. In necropsy at the termination of the dosing period, enlargement of the liver in the 320 mg/kg males and elevation of the limiting ridge in the forestomach in the 320 mg/kg females were observed. In histopathological examinations, centrilobular hypertrophy of the hepatocytes in the 80 and 320 mg/kg males and hyperplasia of the squamous epithelium in the limiting ridge of the forestomach in the 320 mg/kg females were observed. In the recovery study, increased relative liver weight was noted in the 320 mg/kg males as treatment-related change; however, this appeared to be reversible since the severity and incidence were reduced. Based on these results, the main effects of T-7701 were observed in the liver and forestomach with reversibility. Accordingly, the NOEL of T-7701 in rats under the present experimental conditions was estimated to be 20 mg/kg/day, since increased absolute and relative liver weights were observed in the 80 and 320 mg/kg males.