对133种生理相关的环境化学物质进行生殖毒性选和表征
bioRxiv : the preprint server for biology
|April 8, 2024
概括
一个高通量C. elegans测定有效选生殖毒素. 该方法确定了13种化学物质,包括四级化合物 (QAC),强调需要进一步评估生殖毒性.
科学领域:
- 毒理学 毒理学 毒理学
- 发育生物学 发展生物学
- 环境健康 环境健康
背景情况:
- 由于复杂性和可扩展性问题,常规动物模型的繁殖毒性评估具有挑战性.
- 环境化学物质暴露对繁殖构成风险,需要有效的测试方法.
研究的目的:
- 适应和验证C. elegans中的高通量体内染色体分离试验,用于生殖毒性查.
- 使用此试验和公共数据源来描述133种化学品的生殖毒性.
- 将体内发现与ToxCast的体内数据进行比较.
主要方法:
- 适应了C. elegans的体内染色体分离试验,用于高通量查.
- 利用ToxCast和ICE的公开数据来选133种化学品.
- 通过独立的体内胚胎活力试验验证实查结果.
- 将C. elegans测定结果与ToxCast的体外数据进行比较.
主要成果:
- 确定了13种生殖毒素,其中四级化合物 (QAC) 具有高度活性.
- 在C. elegans测定中,在顶部和底部化学物质之间没有观察到生物活性或功效 (AC50) 的显著差异.
- 分类化学物质显示出不同的目标类别,对于高Z分数化学物质,类固醇激素目标的过度代表性.
结论:
- 高通量体内C. elegans模型对于可扩展的生殖毒性评估是有价值的.
- 优先评估QAC对生殖的影响至关重要.
- 在体外和体内试验测定之间目标途径的差异需要进一步调查.
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