Effects of nitrofurazone on spermatogenesis and reproductive toxicity in male rats--part of a collaborative work to determine optimal administration period and endpoints.
To determine an appropriate administration period and sensitive end-points for the evaluation of effects on male fertility, male Sprague-Dawley rats were orally given nitrofurazone, a model compound, at doses of 12.5, 25, or 50 mg/kg/day for 4 weeks, or at doses of 12.5 or 25 mg/kg/day for 9 weeks before mating with untreated females. Copulation and fertility indices were decreased, and pregnancy did not result at doses of 25 mg/kg/day and over with both dosing periods. An increase in preimplantation loss, and decreases in implants and live fetuses were observed with 12.5 mg/kg/day after 9-weeks dosing. However, no reproductive endpoints were affected by the same dose level for 4-weeks. Sperm head count was reduced at doses of 25 mg/kg/day and over with both dosing periods. Histopathology revealed tubular degeneration and interstitial cell hyperplasia at doses of 25 mg/kg/day and over after both periods of dosing. Moreover, failure of spermiation in tubular epithelia was also detected in the 12.5 mg/kg groups. These results suggest that 4-weeks premating exposure is sufficient for evaluation of the effects of nitrofurazone on mate fertility, and the most sensitive endpoint in this 4-week premating-dose study is a histopathological change.
Nishimura
T
T
Safety Research Laboratories, Fukui Research Institute, Ono Pharmaceutical Co., Ltd., Japan.
Aze
Y
Y
Ozeki
Y
Y
D000818:Animals; D004334:Drug Administration Schedule; D005260:Female; D005298:Fertility / Q000187:drug effects*; D008136:Longevity / Q000187:drug effects; D008297:Male; D015337:Multicenter Studies as Topic; D009583:Nitrofurazone / Q000008:administration & dosage* / Q000633:toxicity*; D009929:Organ Size / Q000187:drug effects; D051381:Rats; D017207:Rats, Sprague-Dawley; D013076:Sperm Count / Q000187:drug effects; D013077:Sperm Head / Q000187:drug effects; D013091:Spermatogenesis / Q000187:drug effects*; D013737:Testis / Q000187:drug effects / Q000473:pathology
D009583:Nitrofurazone