COLLABORATIVE WORK TO EVALUATE TOXICITY ON MALE REPRODUCTIVE ORGANS BY REPEATED DOSE STUDIES IN RATS : 4)FADROZOLE HYDROCHLORIDE : AN ORAL 2/4-WEEK MALE REPRODUCTIVE ORGAN TOXICITY STUDY

概要

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Doses of 0, 30 and 60 mg/kg/day of fadrozole hydrochloride (Afema^【○|R】 : non-steroidal aromatase inhibitor, antitumor agent) were given perorally by gavage to HanIbm WIST male rats from 6 or 8weeks of age for 2 weeks, and from 6 weeks of age for 4 weeks. In all treatment groups, reduced weights of seminal vesicle, prostate and epididymis, and degeneration/necrosis of the pachytene spermatocytes in stages VII or VIII seminiferous tubules, were dose-relatedly observed. Effects could also be assessed quantitatively by staging analysis with the result of a reduction in the numbers of stage VII pachytene spermatocytes at 30 and 60 mg/kg/day. Epididymal sperm examination revealed no treatment-related changes in any groups. The effects of 4-week treatment on male reproductive organs were similar to those of 2-week treatment at the same dose levels, except for the weight of seminal vesicle and prostate, which were more reduced by 4-week treatment than by 2-week treatment. There was no notable difference in detectability of toxicity in male reproductive organs between 2-week treatment from 6 weeks of age and 2-week treatment from 8 weeks of age. It was concluded that the changes observed in the rat male reproductive organs following 4 weeks of treatment with fadrozole hydrochloride could be detected also with 2 weeks of treatment.
日本トキシコロジー学会の論文
2000-10-25