几代人之间对物质暴露的内分泌和生殖反应的差异:突出了补充性发现的重要性
1European Chemicals Agency, Hazard Assessment Directorate, Telakkakatu 6, 00150, Helsinki, Finland. ingo.bichlmaier@echa.europa.eu.
Archives of toxicology
|July 18, 2024
概括
生殖毒性研究表明,内分泌和生殖效应很少在同一代人中同时发生. 然而,在父母 (P1) 和发展的第二子孙 (dF2) 世代观察到的效应显示出更强烈的关联,表明独特的代际毒理学模式.
科学领域:
- 毒理学 毒理学 毒理学
- 生殖生物学 生殖生物学
- 内分泌学 在内分泌学.
背景情况:
- 扩展一代生殖毒性研究对于评估化学品安全至关重要.
- 了解代际影响和特定生命阶段的毒理反应至关重要.
- 以前的研究往往假定有毒效应的直接世代连续性.
研究的目的:
- 在毒性研究中分析子代间内分泌和生殖效应的同时发生和强度.
- 为了确定特定的生命阶段或影响类型是否表现出一致的模式.
- 评估传统假设关于代代毒理学连续性的有效性.
主要方法:
- 分析了112个扩展的一代生殖毒性研究.
- 利用二进制矩阵评估了530个观察到的效应和193个显著的关联.
- 使用Jaccard (J) 系数量化关联强度来衡量效应同时发生.
主要成果:
- 在整个数据集中,相关效应很少同时发生 (中位数J = 0.231).
- 跨代同样的效应的关联比不同的效应 (中位数J = 0.222) 强 (中位数J = 0.400).
- 涉及父母 (P1) 和发展第二子孙 (dF2) 世代的关联显示出显著更高的贾卡德系数 (中位数为0.300-0.430).
结论:
- 同一研究中相关的生殖和内分泌影响的同时发生通常是罕见的.
- 涉及P1和dF2世代的关联显著更强,可能是由于长期暴露和概念互动.
- 研究结果强调需要对每代影响进行独立分析,挑战直接毒理连续性的假设.
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