EFFECTS OF NITROFURAZONE ON SPERMATOGENESIS AND REPRODUCTIVE TOXICITY IN MALE RATS : PART OF A COLLABORATIVE WORK TO DETERMINE OPTIMAL ADMINISTRATION PERIOD AND ENDPOINTS (&ltSPECIAL ISSUE&gtTESTICULAR TOXICITY)

To determine an appropriate administration period and sensitive endpoints 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 be...

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Bibliographic Details
Published in:Journal of toxicological sciences 1995, Vol.20(3), pp.341-349
Main Authors: NISHIMURA, Tatsuya, AZE, Yoshiya, OZEKI, Yoshikazu
Format: Article
Language:English
Subjects:
Animals
Drug Administration Schedule
Female
Fertility - drug effects
Longevity - drug effects
Male
Multicenter Studies as Topic
Nitrofurazone - administration & dosage
Nitrofurazone - toxicity
Organ Size - drug effects
Rats
Rats, Sprague-Dawley
Sperm Count - drug effects
Sperm Head - drug effects
Spermatogenesis - drug effects
Testis - drug effects
Testis - pathology
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Summary:To determine an appropriate administration period and sensitive endpoints 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 pre-implantation 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 male fertility, and the most sensitive endpoint in this 4-week premating-dose study is a histopathological change.
ISSN:0388-1350
1880-3989
DOI:10.2131/jts.20.341