Combined effects of maternal exposure to fungicides on behavioral development in F-1-generation mice: 3. Fixed-dose study of imazalil

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.