1,2,3-Trichloropropane (TCP) administered via gavage in corn oil, 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), 30, 60, and 120 mg/kg b.wt. 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 120 mg/kg groups were used in a cross-over mating trial (Task 3) to determine the sex affected by chemical treatment. The F1 generation from control, 30 and 60 as well as 120 mg/kg groups were also evaluated (Task 4).
TCP treatment caused a dose-related impairment of fertility. In the high dose group, fewer pairs delivered third, fourth, and fifth litters and the litters had fewer live pups. Parental body weights were not decreased during Task 2 and 3. During Task 3, treated females mated to control males produced fewer live pups. In both male and female F0 mice, liver weights were increased; female kidney and ovary weights were reduced, and epididymal weight was slightly reduced in the high dose group. Sperm parameters were unchanged.
The fertility index in the second generation pups fed TCP was also significantly reduced. The number of pups trended lower at the high dose, while other fertility endpoints remained unchanged. Some of the interesting findings of the present study included (1) clear demonstration of a progressive effect on fertility and reproduction by TCP treatment (2) a significant reduction in the proportion of male pups born alive in the 120 mg/kg group in the 5th litter. In summary, there is clear evidence that TCP at 120 mg/kg is a reproductive toxicant in Swiss mice in the presence of mild systemic toxicity.
NTIS # PB91129676