Abstract：
Pyrethroid metabolites are widely detectable in urine from the general population, including pregnant women and children. Pyrethroids are neurotoxic and suggested endocrine disruptors. Exposure during vulnerable developmental time windows may have long-term impacts on neurodevelopment.
To evaluate the epidemiological evidence for neurodevelopmental effects related to prenatal and childhood pyrethroid exposure in a systematic review and to assess biological plausibility by evaluating mechanistic evidence.
We searched PubMed and Web of Science up to September 1, 2021 and included original studies published in English in which pyrethroid exposure was measured or estimated during pregnancy or childhood and associations with neurodevelopmental outcomes in the children were investigated. The Navigation Guide Systematic Review Methodology was used to evaluate the epidemiological evidence. For mechanistic evidence, we focused on relevant key events (KEs) suggested in Adverse Outcome Pathways (AOPs) using the OECD-supported AOP-wiki platform. A systematic search combining the KEs with pyrethroids, including 26 individual compounds, was performed in the ToxCast database.
Twenty-five epidemiological studies met the inclusion criteria, 17 presented findings on prenatal exposure, 10 on childhood exposure and two on both exposure windows. The overall body of evidence was rated as \"moderate quality\" with \"sufficient evidence\" for an association between prenatal pyrethroid exposure and adverse neurodevelopment. For childhood exposure, the overall rating was \"low quality\" with \"limited evidence\" because of cross-sectional study design. Regarding mechanistic evidence, we found that pyrethroids are able to interfere with neurodevelopmental KEs included in established AOPs for adverse neurodevelopmental. The evidence was strongest for interference with thyroid hormone (TH) function.
Pyrethroids are probably human developmental neurotoxicants and adverse impacts of pyrethroid exposure on neurodevelopment are likely at exposure levels occurring in the general population. Preventive measures to reduce exposure among pregnant women and children are warranted.
To evaluate the epidemiological evidence for neurodevelopmental effects related to prenatal and childhood pyrethroid exposure in a systematic review and to assess biological plausibility by evaluating mechanistic evidence.
We searched PubMed and Web of Science up to September 1, 2021 and included original studies published in English in which pyrethroid exposure was measured or estimated during pregnancy or childhood and associations with neurodevelopmental outcomes in the children were investigated. The Navigation Guide Systematic Review Methodology was used to evaluate the epidemiological evidence. For mechanistic evidence, we focused on relevant key events (KEs) suggested in Adverse Outcome Pathways (AOPs) using the OECD-supported AOP-wiki platform. A systematic search combining the KEs with pyrethroids, including 26 individual compounds, was performed in the ToxCast database.
Twenty-five epidemiological studies met the inclusion criteria, 17 presented findings on prenatal exposure, 10 on childhood exposure and two on both exposure windows. The overall body of evidence was rated as \"moderate quality\" with \"sufficient evidence\" for an association between prenatal pyrethroid exposure and adverse neurodevelopment. For childhood exposure, the overall rating was \"low quality\" with \"limited evidence\" because of cross-sectional study design. Regarding mechanistic evidence, we found that pyrethroids are able to interfere with neurodevelopmental KEs included in established AOPs for adverse neurodevelopmental. The evidence was strongest for interference with thyroid hormone (TH) function.
Pyrethroids are probably human developmental neurotoxicants and adverse impacts of pyrethroid exposure on neurodevelopment are likely at exposure levels occurring in the general population. Preventive measures to reduce exposure among pregnant women and children are warranted.
摘要：
拟除虫菊酯代谢物在一般人群的尿液中广泛检测到，包括孕妇和儿童。拟除虫菊酯具有神经毒性，提示内分泌干扰物。在脆弱的发育时间窗口中暴露可能会对神经发育产生长期影响。
在系统评价中评估与产前和儿童拟除虫菊酯暴露相关的神经发育影响的流行病学证据，并通过评估机理证据评估生物学合理性。
我们搜索了截至2021年9月1日的PubMed和WebofScience，并纳入了以英文发表的原始研究，其中在怀孕或童年期间测量或估计拟除虫菊酯暴露，并调查了与儿童神经发育结果的关联。使用导航指南系统审查方法来评估流行病学证据。对于机械证据，我们使用OECD支持的AOP-wiki平台,重点关注不良结果途径(AOP)中建议的相关关键事件(KE).结合KEs和拟除虫菊酯的系统搜索，包括26个单独的化合物，在ToxCast数据库中执行。
25项流行病学研究符合纳入标准，17介绍了产前暴露的结果，10在童年曝光和两个曝光窗口。关于产前拟除虫菊酯暴露与不良神经发育之间的关联，总体证据被评为“中等质量”和“充分证据”。对于童年的曝光，由于横断面研究设计，总体评级为“低质量”，“证据有限”。关于机械证据，我们发现拟除虫菊酯能够干扰已建立的AOP中包含的神经发育中的KE，以治疗不良的神经发育。干扰甲状腺激素（TH）功能的证据最强。
拟除虫菊酯可能是人类发育神经毒物，拟除虫菊酯暴露对神经发育的不利影响可能发生在普通人群中的暴露水平。有必要采取预防措施，减少孕妇和儿童的接触。
在系统评价中评估与产前和儿童拟除虫菊酯暴露相关的神经发育影响的流行病学证据，并通过评估机理证据评估生物学合理性。
我们搜索了截至2021年9月1日的PubMed和WebofScience，并纳入了以英文发表的原始研究，其中在怀孕或童年期间测量或估计拟除虫菊酯暴露，并调查了与儿童神经发育结果的关联。使用导航指南系统审查方法来评估流行病学证据。对于机械证据，我们使用OECD支持的AOP-wiki平台,重点关注不良结果途径(AOP)中建议的相关关键事件(KE).结合KEs和拟除虫菊酯的系统搜索，包括26个单独的化合物，在ToxCast数据库中执行。
25项流行病学研究符合纳入标准，17介绍了产前暴露的结果，10在童年曝光和两个曝光窗口。关于产前拟除虫菊酯暴露与不良神经发育之间的关联，总体证据被评为“中等质量”和“充分证据”。对于童年的曝光，由于横断面研究设计，总体评级为“低质量”，“证据有限”。关于机械证据，我们发现拟除虫菊酯能够干扰已建立的AOP中包含的神经发育中的KE，以治疗不良的神经发育。干扰甲状腺激素（TH）功能的证据最强。
拟除虫菊酯可能是人类发育神经毒物，拟除虫菊酯暴露对神经发育的不利影响可能发生在普通人群中的暴露水平。有必要采取预防措施，减少孕妇和儿童的接触。
