Combined effects of maternal exposure to fungicides on behavioral development in F1 -generation mice: 3. Fixed-dose
Toyohito Tanaka1, Jin Suzuki1, Akiko Inomata2
1Division of Toxicology, Department of Pharmaceutical and Environmental Sciences, Tokyo Metropolitan Institute of Public Health, Shinjuku-ku, Tokyo, Japan.
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 F1 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 F1 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 F1 generation after finishing chemical administration have been caused by the IMZ concentration of maternal exposure, with TBZ's effects being complementary.
