Combined Effects of Dinotefuran and Piperonyl Butoxide on Behavioral Development in an F ₁ ‐Generation Toxicity Study in Mice

Background Few published studies have reported on the 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 a combined treatment with 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), DIN 0.005% + PBO 0.03%, DIN 0.01% + PBO 0.03%, and DIN 0.02% + 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 behavioral development during the lactation period, surface righting on PND 4 and olfactory orientation route on PND 14 indicated a significantly high score in the DIN 0.02% + PBO 0.03% group in male offspring. In female offspring, olfactory orientation route and time on PND 14 indicated a significantly high score in the DIN 0.02% + PBO 0.03% group. For exploratory behavior in the F 1 ‐generation offspring, several variables indicated significant effects in male and female offspring. In the spontaneous behavior of males in the F 1 generation, the parallel lines among the control and treatment groups indicated significant distances in total distance, movement time, and number of rearing. Conclusions The dose levels of DIN with PBO in the present study produced several adverse effects on neurobehavioral parameters in F 1 generation mice at lower dose levels than DIN alone.