1, 2, 4, 5-Tetrachlorobenzene (TCB) was tested for its effects on fertility and reproduction in Swiss CD-1 mice using the continuous breeding protocol. Male and female mice (F0) were continuously exposed for a 7-day precohabitation and a 98-day cohabitation period (Task 2) to TCB at levels of 0.028, 0.072, and 0.18% w/w in the diet.
TCB treatment at 0.18% was significantly more toxic than anticipated. Nineteen of the twenty high-dose females died (or were humanely sacrificed) and almost all of these deaths occurred at parturition. None of the males died. In the 0.072% group, a 9% (significant) decrease in the number of live pups per litter was noted; no changes were observed in pup weights, proportion of male pups, or days to deliver each litter.Task 3, the determination of the affected sex, was not conducted, given the small change in litter size. At terminal sacrifice, the average liver weight and the liver- to-body weight ratio in F0 males exposed to 0.18% TCB were almost twice the control values. In the F1 generation, liver and kidneys were enlarged in both sexes exposed to 0. 072% TCB. Sperm abnormalities were greater in the 0.18% TCB group by 40%, compared to controls. Seminal vesicle weight was increased in the high-dose-treated males.
The second generation was reared consuming control diet, or diet with 0.072% TCB. At sexual maturity, there was no difference in mating, litter size, pup weight (absolute or adjusted), or dam weight. At F1 necropsy, there was an increase in the absolute and relative weights of liver, kidneys, and testis in the 0.072% TCB group, with similar increases in female liver and kidneys weights. There was no change in F1 female estrual cycle parameters.
TCB, under the present experimental conditions, exerted mild reproductive toxicity in the presence of considerable systemic toxicity. Thus, TCB is a reproductive toxicant in the presence of significant systemic toxicity.
NTIS # PB92-128388