Collaborative work to evaluate toxicity on male reproductive organs by repeated dose studies in rats 18). Comparative 4 and 2 weeks oral repeated dosing studies on male reproductive organs in rats treated with 5-fluorouracil.
Oral repeated toxicity studies were conducted to compare the effects of 5-fluorouracil (5-FU) administered for 4 or 2 weeks on male reproductive organs of Sprague-Dawley (SD) rats. In both studies, decrease of feces, abnormal fur and emaciation were observed. On gross autopsy examination, softening/atrophy of the testis as well as atrophy of accessory reproductive organs were noted, and absolute organ weights of male reproductive organs were almost all reduced in both studies. Histopathologically, degeneration of the seminiferous epithelium in the testis and desquamated cell debris in the epididymal ducts were apparent after both time periods. In the 2-week study, furthermore, exfoliation of the seminiferous epithelium, formation of multinucleated giant cells and vacuolation of Sertoli cells in the seminiferous tubules in the testis, and decrease of sperms in the epididymal ducts were observed. The present results indicated that a 2-week study is sufficient to detect effects on the male reproductive organs of 5-FU treatment. In our study, however, changes in associated parameters after 2-week treatment of 8-week-old rats were greater than those after 4 weeks in 6-week-old rats. Thus, for detection of 5-FU-induced male reproductive toxicity, we can evaluate more accurately by using maturated rats of the same age.
Inomata
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Department of Preclinical Science, Nippon Roche Research Center, 200 Kajiwara, Kamakura, Kanagawa 247-8530, Japan.
Matsumoto
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Horii
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D000818:Animals; D000964:Antimetabolites, Antineoplastic / Q000008:administration & dosage / Q000633:toxicity*; D001835:Body Weight / Q000187:drug effects; D004305:Dose-Response Relationship, Drug; D004435:Eating / Q000187:drug effects; D004822:Epididymis / Q000187:drug effects / Q000473:pathology; D005472:Fluorouracil / Q000008:administration & dosage / Q000633:toxicity*; D008297:Male; D009929:Organ Size / Q000187:drug effects; D011467:Prostate / Q000187:drug effects / Q000473:pathology; D051381:Rats; D017207:Rats, Sprague-Dawley; D012669:Seminal Vesicles / Q000187:drug effects / Q000473:pathology; D012670:Seminiferous Epithelium / Q000187:drug effects / Q000473:pathology; D012708:Sertoli Cells / Q000187:drug effects / Q000473:pathology; D013737:Testis / Q000187:drug effects* / Q000473:pathology; D013997:Time Factors; D018675:Toxicity Tests
D000964:Antimetabolites, Antineoplastic; D005472:Fluorouracil