Dietary two-generation reproduction study of thiabendazole in Sprague-Dawley rats

The potential reproductive toxicity of the fungicide and anthelmintic thiabendazole (TBZ) was assessed in Sprague-Dawley rats for two generations. Doses of 10, 30 or 90 mg/kg/day were administered by way of the diet beginning at 8 wk of age for the F0 generation and postnatal wk 4 for the F1 generation and continuing until the animals were killed. Concentrations of TBZ in the diet were adjusted weekly, except during the gestation and lactation intervals when concentrations were held constant. There were no TBZ-related deaths or adverse physical signs during the study. TBZ-related effects consisted of decreases in average body weight gains and food consumption in the middle and high dose groups. In both the F0 and F1 generations during the premating and post-cohabitation periods, the effects in the middle-dose group were observed only in males and were generally slight in magnitude (food consumption 3-5% below control, weight gain 7-18% below control), whereas the effects in the high dose group occurred in both sexes and were slight to moderate in magnitude (food consumption 9-13% below control, weight gain 13-46% below control). During gestation of the F0 females there were slight decreases in average weight gain and food consumption (8% and 4-16% below control, respectively); a similar effect on food consumption, but not weight gain, occurred in the F1 generation. There were no effects on F0 or F1 reproductive performance (including indices of mating, fecundity, fertility, length of gestation, litter size, birth weight, and post-implantation survival), nor were any histomorphological changes observed in the reproductive tissues of animals in the high dose group. There was no evidence of developmental toxicity in the TBZ-exposed F1 or F2 generations, except for slight decreases in average pup weights between postnatal days 4 and 21 in the high dose group (5-10% below control). The NOAEL (no-observed-adverse-effect level) for all developmental, growth, survival and reproductive performance parameters assessed in this study was 10 mg/kg/day.