© 1996 Oxford University Press
research-article |
Nitrofurazone: Reproductive Assessment by Continuous Breeding in Swiss Mice1
Laboratory of Reproductive Toxicology, Chemistry and life Sciences Division, Center for Life Sciences and Toxicology, Research Triangle Institute P.O. Box 12194, Research Triangle Park, North Carolina 27709-2194 *Developmental and Reproductive Toxicology Croup, National Toxicology Program, National Institute of Environmental Health Sciences P.O. Box 12233, Research Triangle Park, North Carolina 27709
Received March 1, 1996; accepted August 14, 1996
Nitrofurazone (NTFZ), a nitrofuran antibiotic, was evaluated for reproductive toxicity in Swiss CD-1 mice using the Reproductive Assessment by Continuous Breeding protocol. Male and female mice were cohabited for 15 weeks and exposed to NTFZ in feed at concentrations of 0, 100, 375, and 750 ppm (14–102 mg/kg/day). F0 750-ppm breeding pairs had significantly reduced fertility after 7 days of exposure to NTFZ (17% fertile compared to 98% for control pairs) and were infertile after the second litter. F0 mid-dose pairs had progressively decreasing fertility (47% by the fifth litter), reduced litter size, and reduced proportion of pups born alive. Crossover breeding of control and high-dose F0 animals confirmed infertility in high-dose males and reduced litter size and pup weight in high-dose females when compared to the controlxcontrol group. At necropsy, there were no effects on body weight, but F0 males had reduced testis weight at the high dose and reduced epididymal sperm concentration and abnormal sperm morphology at all doses of NTFZ. Increased liver as well as kidney and adrenal weights (combined) were observed at 375 and 750 ppm; hepatic hypertrophy was noted microscopically at 750 ppm. F0 females had reduced body weight, hepatic hypertrophy, and altered estrous cycles at 750 ppm and reduced ovarian weight at all doses. In the second generation, F1 mice at 375 ppm had reduced postnatal survival and body weight and produced smaller F2 litters compared to control mice. At necropsy, F1 males had reduced testes weight and epididymal sperm concentration, abnormal sperm morphology, hepatic hypertrophy at 375 ppm, and borderline nephropathy at 100 and 375 ppm. F1 females had decreased body, liver, and ovarian weight at 375 ppm and altered estrous cycles at 100 and 375 ppm. Thus, NTFZ at 
100 ppm ( 14 mg/kg/day) caused adverse reproductive effects in F0 male and female and F1 female mice in the presence of relatively mild systemic toxicity.