Reproductive and Neurobehavioral Effects of Combined Exposure to Dinotefuran and Piperonyl Butoxide in an F 1 Generation of Mice

ABSTRACT Background Few published studies are reported for reproductive and neurobehavioral toxicity of combined exposure to neonicotinoid insecticides and synergists in mammals. This study aimed to evaluate the reproductive and neurobehavioral effects of combined dinotefuran (DIN) and piperonyl butoxide (PBO) in an F 1 ‐generation toxicity study in mice. Methods DIN and PBO were given in the diet to provide levels of 0% (control), PBO 0.03%, DIN 0.012% + PBO 0.03%, and DIN 0.024% + PBO 0.03% from 5 weeks of age of the F 0 generation to 11 weeks of age of the F 1 generation in mice. Selected reproductive and neurobehavioral parameters were measured in the F 1 generation. Results For exploratory behavior in the F 0 generation, the number of horizontal activities increased with a statistically significant dose‐related response in adult males. For exploratory behavior in the F 1 generation, the total distance, movement time, average speed, and average time of movement increased with statistically significant dose‐related responses in adult males. In the spontaneous behavior of males in the F 1 generation, the parallel lines during the control and treatment groups indicated significant distances in the total distance, average speed, and average time of movement. Conclusions The dose levels of DIN with PBO in the present study affected exploratory and spontaneous behavior at lower dose levels than those observed in previous studies with the single administration of DIN and PBO. Therefore, the dose level of PBO (0.03%, approximately 44–116 mg/kg body weight/day) is estimated to have a synergistic effect on DIN exposure.