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.