para-Nitrobenzoic acid (p-NBA) administered via dosed feed, was tested for its effects on fertility and reproduction in Swiss CD-1 mice according to the Continuous Breeding protocol. Based on results of a dose-finding study (Task 1), 0.35, 0.75, and 1.50% levels were chosen to investigate effects on fertility and reproduction. Male and female mice were continuously exposed for a 7-day pre-cohabitation and a 98-day cohabitation period (Task 2). Subsequently, the control and 0.75% groups were used in a cross-over mating trial (Task 3) to determine the sex affected by chemical treatment. The F1 generation from control, 0.35, and 0.75% as well as 1.50% groups were also evaluated (Task 4). p-NBA treatment caused a dose-related impairment of both fertility and reproduction. At 0.75 and 1.50% levels, almost all reproductive parameters were adversely affected. Simultaneously, p-NBA caused reduced weight gain, so that by the end of the study, high-dose female and male body weights were 93% and 88%, respectively, of the corresponding control values.
Test results from the crossover mating trial showed that fertility and reproductive performance of 0.75% p-NBA treated males X control females was essentially the same as control males X control females. However, in the litters delivered by the females receiving 0.75% p-NBA and cross-mated with control males, the number of live pups per litter, proportion of pups born alive and both absolute and adjusted live pup weights were significantly reduced. These findings show that p-NBA affects the female reproductive system and/or fetal development.
Reproductive performance of second generation animals was also impaired and the response was very similar to p-NBA mediated adverse effects noted in F0 animals.
NTIS # PB90253766