Combined effects of maternal exposure to fungicides on behavioral development in F₁‐generation mice: 3. Fixed‐dose study of imazalil

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Background Few published studies are reported for the neurobehavioral toxicity of combined exposure to fungicides in mammals. This study was aimed to re‐evaluate the reproductive and neurobehavioral effects of maternal exposure to combined imazalil (IMZ) and thiabendazole (TBZ) with fixed‐dose of IMZ in mice. Methods IMZ/TBZ was given in the diet to provide levels of 0%/0% (control), 0.006%/0.006% (IMZ/TBZ), 0.006%/0.018%, and 0.006%/0.054% during the gestation and lactation periods. Selected reproductive and neurobehavioral parameters were measured in the F 1 generation. Results No adverse effect of IMZ/TBZ was observed in litter size, litter weight, or sex ratio at birth. Concerning behavioral developmental parameters, the time required of olfactory orientation was accelerated significantly in higher‐dose groups in female offspring on postnatal day 14 in a dose‐related manner. Exploratory behavior examination indicated that the frequency of mice with urination increased in a significantly dose‐related manner in male offspring. After weaning, any variables of exploratory behavior indicated no significant effects in both sexes of adult mice in the F 1 generation. In spontaneous behavior, the longitudinal pattern of total distance was not parallel (different pattern) among the control and IMZ/TBZ treatment groups in adult males. Conclusions The results from these series of combined exposure studies of IMZ/TBZ suggest that the main effects on exploratory and spontaneous behavior of adult mice in the F 1 generation after finishing chemical administration have been caused by the IMZ concentration of maternal exposure, with TBZ's effects being complementary.