Neonicotinoids (NNs), a widely used class of systemic pesticides, are regarded as exhibiting selective toxicity in insects. However, NNs are suspected of exerting adverse effects on mammals as well, including humans. To date, only adult male animal models have been subjected to general toxicity studies of NNs; fetuses have yet to be considered in this context. Here, we focused on the NN clothianidin (CLO) for the first quantitative LC-MS/MS analysis of maternal-to-fetal transfer and residual property of once-daily (single or multiple days), orally administered CLO and its metabolites in mice. The results revealed the presence of CLO and its five metabolites at approximately the same respective blood levels in both dams and fetuses. In the dams, CLO showed a peak value 1 h after administration, after which levels rapidly decreased at 3 and 6 h. In the fetuses of each group, levels of CLO were almost the same as those observed in the corresponding dams. The present results clearly demonstrated rapid passage of CLO through the placental barrier. However, metabolite-dependent differences observed in blood pharmacokinetics and residual levels. This is the first quantitative demonstration of the presence of CLO and its metabolites in fetal mouse blood.

中文翻译：

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小鼠新烟碱类农药噻虫胺及其代谢物母胎转移的定量阐明

新烟碱类 (NNs) 是一类广泛使用的内吸性杀虫剂，被认为对昆虫具有选择性毒性。然而，人们怀疑神经网络也会对哺乳动物（包括人类）产生不利影响。迄今为止，只有成年雄性动物模型进行了神经网络的一般毒性研究；在这方面尚未考虑胎儿。在这里，我们专注于 NN 噻虫胺 (CLO)，用于首次定量 LC-MS/MS 分析母胎转移和每天一次（单天或多天）口服给药的 CLO 及其代谢物在小鼠体内的残留特性. 结果显示，在母畜和胎儿中，CLO 及其五种代谢物的血液水平大致相同。在大坝中，CLO 在给药后 1 小时出现峰值，此后水平在 3 和 6 小时迅速下降。在每组的胎儿中，CLO 的水平与在相应大坝中观察到的几乎相同。目前的结果清楚地表明 CLO 快速通过胎盘屏障。然而，在血液药代动力学和残留水平中观察到代谢物依赖性差异。这是首次定量证明胎鼠血液中存在 CLO 及其代谢物。