Risk assessment of pyridaben exposure on neurodevelopment of offspring by using TRAEC strategy

Abstract

As a mitochondrial complex I inhibitor, pyridaben has been found to have the adverse effects on spermatogenesis, embryonic development and neurons. However, the effects of pyridaben exposure on offspring neurodevelopment are still insufficient. In this study, the risk of pyridaben exposure on the neurodevelopment of offspring was assessed by one novel strategy called Targeted Risk Assessment of Environmental Chemicals (TRAEC), which give a comprehensive assessment based on four dimensions (the reliability, correlation, outcome fitness and integrity) of published and researchers’ own evidences. Six studies (one epidemiological study, two in vivo studies and three in vitro studies) and our supplementary evidences were finally enrolled for a final scoring system. After the evidence scoring, a composite risk score of 5.64 was gotten, indicating a medium-level risk of pyridaben on the neurodevelopmental in offspring. In our study, a supplement about the neurodevelopmental toxicity of pyridaben was conducted by using constructed NE-4C stem cells models. The results showed that pyridaben inhibited the viability and proliferation capacity of neural stem cells with an IC₅₀ value of 0.58 μM. After treatment with pyridaben for 24 h, the cell cycle of NE-4C cells was significantly increased in the S phase but decreased in the G2 phase, and its apoptosis had a significant increase in the total percentage of early apoptotic cells. Moreover, we found that pyridaben could change different neurons and glial cell markers such as Dnmt3b, Kmt1a and Kdm6a. Taken together, our study gives a comprehensive evaluation of the neurodevelopmental toxicity of pyridaben by using TRAEC strategy and highlights the necessity of enhancing the risk management measures for pyridaben.