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Abstract for RACB89063

Nitrofurantoin: Reproduction and Fertility Assessment in CD-1 Mice When Administered via Feed

CASRN: 67-20-9
Chemical Formula: C8H6N4O5
Molecular Weight: 238.159
Report Date: August 1989


The following abstract presents results of a study conducted by a contract laboratory for the National Toxicology Program. The findings were not evaluated in accordance with the levels of evidence for reproductive or developmental criteria established by NTP in March 2009. The findings and conclusions for this study should not be construed to represent the views of NTP or the U.S. Government.

Nitrofurantoin, administered via dosed feed, was tested for its effects on fertility and reproduction in Swiss CD-l mice according to the Continuous Breeding protocol. Based on results of a dose-finding study (Task 1), 0.03, 0.06, and 0.12% (300, 600, and 1,200 ppm) levels were chosen to investigate effects on fertility and reproduction. Male and female mice were continuously exposed for a 7-day precohabitation and a 98-day cohabitation period (Task 2). Subsequently, the control and 0.12% groups were used in a cross-over mating trial (Task 3) to determine the sex affected by chemical treatment. The F1 generation from control, 0.06, and 0.12% groups were also evaluated (Task 4). Nitrofurantoin treatment, at up to 0.12% concentrations, had no apparent effect on parental fertility, number of litters per pair, proportion of pups born alive, sex of live pups, neonatal body weights, and postnatal survival. Nitrofurantoin at 0.12% in feed, significantly reduced dam body weight at delivery and lactation, number of live pups per litter, and pup body weights at postnatal days 7 to 21. The cross-over mating trial did not reveal any significant effects on mating, fertility or reproduction. Nitrofurantoin disrupted the estrual cycle in the F0 females; there was a significant increase in the percent of vaginal smears showing estrus, and a decrease in the percent of smears indicating diestrus.

All parental mice were necropsied. Female body weight was slightly reduced at 0.12%, as was epididymal sperm motility; absolute and adjusted kidney weights of both sexes were increased significantly at 0.12%. There were also testicular lesions in the 0.12% group.

The F1 generation showed significant reductions in fertility and live litter size at the 0.12% dose level. Nitrofurantoin at 0.12% significantly increased F1 adjusted kidney weights (both sexes) and reduced testis, epididymis and cauda epididymis weights as well as epididymal sperm concentration and motility, and produced testicular lesions.

These data show that Nitrofurantoin exhibited reproductive toxicity in the presence of systemic effects.

NTIS # PB93-175354