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© 1992 Oxford University Press

research-article

Reproductive Toxicity of Sulfamethazine in Swiss CD-1 Mice during Continuous Breeding

JERRY R. REEL*,1, ROCHELLE W. TYL*, A. DAVIS LAWTON* and JAMES C. LAMB, IV{dagger},2

*Chemistry and Life Sciences Group, Research Triangle Institute P.O. Box 12194, Research Triangle Park; North Carolina 27709 {dagger}Developmental and Reproductive Toxicology Group, National Toxicology Program, National Institute of Environmental Health Sciences P.O. Box 12233, Research Triangle Park, North Carolina 27709

Received July 29, 1991; accepted November 21, 1991

Sulfamethazine (SMZ) was evaluated for reproductive toxicity in Swiss CD-1 mice using a continuous breeding protocol. SMZ was administered in the diet at 0, 0.25, 0.5, or 1% (w/w), which represented an average daily intake of 0, 313, 625, or 1250 mg SMZ/kg/day, respectively. Exposure of F0 male and female mice to 1% SMZ for 126 days resulted in a significant decrease in the mean number of live pups per litter and the number of litters produced (task 2); the percentage pups born alive to 1% SMZ females showed a nonsignificant decrease versus control females. The effects on fertility were rapid to onset (1 to 4 weeks) and cumulative in nature. F0 male and female body weights were slightly depressed from 3 weeks to the end of the study. The crossover mating trial (task 3) revealed that the adverse effect on ferility involved both treated partners in that litter size decreased when either 1% SMZ males were bred to control females or 1% SMZ females were mated with control males. After approximately 155 days of exposure of F0 mice to 1% SMZ, the terminal body weight of 1% SMZ females was significantly decreased and that of 1% SMZ males showed a nonsignificant decrease. In addition, the liver weight to body weight ratio of the males was increased. Further, the prostate and seminal vesicle weight to body weight ratios were decreased in 1% SMZ males relative to control males. No treatment-related gross or histopathological lesions were noted for the pituitary or reproductive organs of either sex. Sperm assessment indicated no significant difference in the epididymal sperm concentration or percentage motile or abnormal sperm. In conclusion, SMZ was found to be a reproductive toxicant in the male and female Swiss CD-1 mouse, albeit at relatively high dietary intake (1250 mg/kg/day), and in the presence of mild systemic toxicity.


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