Effect of tridiphane on reproductive parameters in Fischer 344 rats

Reproductive parameters in Fischer 344 rats were evaluated following dietary administration of tridiphane for 2 successive generations. Male and female rats in the fO generation were maintained on test diets formulated to provide 0, 1, 5, or 30 mg tridiphane/kg per day for 104 days starting at 6 weeks of age. The rats were allowed to mate twice to produce the f1a and f1b litters. Offspring from the f1b litters were maintained on test diets for 125 days and then mated to produce the f2a and f2b litters. Reproductive parameters including fertility, litter size and growth and survival of the pups were monitored. Selected weanlings were examined for gross and histologic lesions. Treatment related effects in the f0 adults were limited to the 30 mg/kg dose group and consisted of increases in relative liver weights in both sexes and depressed body weights in females. Liver weight relative to body weight was elevated in weanlings of both sexes in the f1a (30 mg/kg) litters but only in male offspring in the f1b litters. In the f1 adult females from the 30 mg/kg per day group, body weights were depressed throughout the 125-day treatment period and during lactation of both the f2a and the f2b litters. In the second generation, only male weanlings from the f2a litters, 5 mg/kg per day group had elevated (relative) liver weights. No consistent adverse effects on reproduction, fertility, or neonatal growth or survival were observed in either the f1 or f2 generations, and gross and histological examination of livers from weanlings did not reveal any treatment related lesions.