Related Experiment Video
Updated: Jul 10, 2026
Protocols for Testing the Toxicity of Novel Insecticidal Chemistries to Mosquitoes
Published on: February 13, 2019
Combined Effects of Dinotefuran and Piperonyl Butoxide on Behavioral Development in an F1-Generation Toxicity Study
Toyohito Tanaka1, Motoki Hojo1, Akiko Inomata2
1Division of Toxicology, Department of Pharmaceutical and Environmental Sciences, Metropolitan Institute of Public Health, Tokyo, Japan.
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 F1-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 F0 generation to 11 weeks of age of the F1 generation in mice. Selected reproductive and neurobehavioral parameters were measured in the F1 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 F1-generation offspring, several variables indicated significant effects in male and female offspring. In the spontaneous behavior of males in the F1 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 F1 generation mice at lower dose levels than DIN alone.
Insights
Combined exposure to dinotefuran (DIN) and piperonyl butoxide (PBO) insecticides caused adverse neurobehavioral effects in mice offspring. These effects occurred at lower doses than dinotefuran alone, highlighting potential risks of insecticide synergists.
Area of Science:
- Toxicology
- Neuroscience
- Environmental Health
Background:
- Limited research exists on the combined reproductive and neurobehavioral toxicity of neonicotinoid insecticides and synergists in mammals.
- This study addresses the knowledge gap concerning the effects of dinotefuran (DIN) and piperonyl butoxide (PBO) co-exposure.
Purpose of the Study:
- To evaluate the reproductive and neurobehavioral effects of combined DIN and PBO treatment in a multigenerational mouse study.
- To assess the impact on the F1 generation following parental exposure during development.
Main Methods:
- F0 generation mice were fed diets containing varying levels of DIN and PBO (0%, 0.005% DIN + 0.03% PBO, 0.01% DIN + 0.03% PBO, 0.02% DIN + 0.03% PBO) from 5 weeks to 11 weeks of age.
- The F1 generation offspring were assessed for selected reproductive and neurobehavioral parameters.
- Neurobehavioral assessments included measures of behavioral development (surface righting, olfactory orientation) and exploratory/spontaneous behavior.
Main Results:
- Significant alterations in behavioral development were observed in male and female F1 offspring, particularly in the highest DIN + PBO exposure group (0.02% DIN + 0.03% PBO).
- Specific findings included high scores in olfactory orientation and altered spontaneous behavior (total distance, movement time, rearing) in male offspring.
- The combined exposure demonstrated significant effects on multiple neurobehavioral variables in both male and female F1 generation mice.
Conclusions:
- Combined exposure to dinotefuran and piperonyl butoxide at the tested doses induced adverse neurobehavioral effects in the F1 generation mice.
- These adverse effects were observed at lower dose levels compared to those reported for dinotefuran exposure alone, suggesting a potentiating role of the synergist.
