{"title":"Combined Effects of Dinotefuran and Piperonyl Butoxide on Behavioral Development in an F1-Generation Toxicity Study in Mice","authors":"Toyohito Tanaka, Motoki Hojo, Akiko Inomata","doi":"10.1002/bdr2.70086","DOIUrl":null,"url":null,"abstract":"<div>\n \n \n <section>\n \n <h3> Background</h3>\n \n <p>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<sub>1</sub>-generation toxicity study in mice.</p>\n </section>\n \n <section>\n \n <h3> Methods</h3>\n \n <p>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<sub>0</sub> generation to 11 weeks of age of the F<sub>1</sub> generation in mice. Selected reproductive and neurobehavioral parameters were measured in the F<sub>1</sub> generation.</p>\n </section>\n \n <section>\n \n <h3> Results</h3>\n \n <p>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<sub>1</sub>-generation offspring, several variables indicated significant effects in male and female offspring. In the spontaneous behavior of males in the F<sub>1</sub> generation, the parallel lines among the control and treatment groups indicated significant distances in total distance, movement time, and number of rearing.</p>\n </section>\n \n <section>\n \n <h3> Conclusions</h3>\n \n <p>The dose levels of DIN with PBO in the present study produced several adverse effects on neurobehavioral parameters in F<sub>1</sub> generation mice at lower dose levels than DIN alone.</p>\n </section>\n </div>","PeriodicalId":9121,"journal":{"name":"Birth Defects Research","volume":"118 7","pages":""},"PeriodicalIF":2.0000,"publicationDate":"2026-07-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":"0","resultStr":null,"platform":"Semanticscholar","paperid":null,"PeriodicalName":"Birth Defects Research","FirstCategoryId":"3","ListUrlMain":"https://onlinelibrary.wiley.com/doi/10.1002/bdr2.70086","RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"Q4","JCRName":"DEVELOPMENTAL BIOLOGY","Score":null,"Total":0}
引用次数: 0
Abstract
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.
期刊介绍:
The journal Birth Defects Research publishes original research and reviews in areas related to the etiology of adverse developmental and reproductive outcome. In particular the journal is devoted to the publication of original scientific research that contributes to the understanding of the biology of embryonic development and the prenatal causative factors and mechanisms leading to adverse pregnancy outcomes, namely structural and functional birth defects, pregnancy loss, postnatal functional defects in the human population, and to the identification of prenatal factors and biological mechanisms that reduce these risks.
Adverse reproductive and developmental outcomes may have genetic, environmental, nutritional or epigenetic causes. Accordingly, the journal Birth Defects Research takes an integrated, multidisciplinary approach in its organization and publication strategy. The journal Birth Defects Research contains separate sections for clinical and molecular teratology, developmental and reproductive toxicology, and reviews in developmental biology to acknowledge and accommodate the integrative nature of research in this field. Each section has a dedicated editor who is a leader in his/her field and who has full editorial authority in his/her area.