Piperonyl butoxide (PBO) an insecticide synergist was evaluated in a guideline multigenerational toxicity study in rats. F0 and F1 adult generations consisted of groups of 26 male and 26 female CD (Sprague Dawley) rats that were exposed to PBO in the diet at concentrations of 0, 300, 1000 or 5000 ppm for 85 (F0) or 83 (F1) days prior to cohabitation and throughout two mating periods (F1a, F2a and F1b, F2b). Exposure to test diets continued through the mating, gestation, and lactation periods for the females. F2 generation pups were euthanized following weaning. There were no effects on survival, clinical observations, gross or histological findings, fertility, pup viability, lactation indices or sex ratio in adults or pups in any generation. All effects of PBO occurred in the 5000-ppm exposure group. These effects included reduced body weight gains for F0 and F1 males and females during pre-cohabitation resulting in reduced body weights during both gestation periods. Food consumption of the F1b group males was slightly or significantly less than control values from week 3 onward. F1a generation pup weights were reduced on days 4, 7, 14 and 21 postpartum. Pup weights in the F1 and F2 generations were significantly reduced on days 14 and 21 postpartum when diets were being consumed by pups. The no-observable-adverse-effect level (NOAEL) for general toxicity was 1000 ppm based on reductions in body weights (parental and offspring) at 5000 ppm; and the NOAEL for reproductive toxicity was 5000 ppm with no direct effects on reproduction.
Keywords: Multigenerational; Piperonyl butoxide; Rat; Reproductive toxicity.
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