Reproductive and neurobehavioural effects of thiabendazole administered to mice in the diet

Thiabendazole was given in the diet to provide levels of 0 (control), 0.031, 0.125, and 0.5% from 5 weeks of age of the F0 generation to 9 weeks of age of the F1 generation in mice, and selected reproductive and neurobehavioural parameters were measured. The average litter size and weight were significantly reduced in the high-dose group at birth. No adverse effects were observed in the sex ratio at birth. The average body weight of offspring was significantly increased in the low-dose group during the late lactation period, and was significantly reduced in the high-dose group during the lactation period. In the assessment of neurobehavioural parameters, surface righting at postnatal day (PND) 7 was significantly delayed in a dose-related manner in both sexes. Swimming limb movement at PND 14 and olfactory orientation at PND 14 were significantly depressed in the high-dose group in both sexes. In movement activity at 3 weeks of age in the F1 generation, vertical time and number of defaecations were significantly decreased in the high-dose group in female offspring. Several adverse effects on reproductive and neurobehavioural parameters were produced at the highest dose level of thiabendazole used in the present study (equivalent to 700-1800 mg/kg bw/day). Slight, dose-related delays were also seen in surface-righting ability at the two lower dose levels. The lowest close level (equivalent to 50-180 mg/kg bw/day) is approximately 500 times the current acceptable daily intake (ADI) of 0-0.1 mg/kg bw.