Non-monotonic dose-response relationships and endocrine disruptors: a qualitative method of assessment.
Non-monotonic dose-response relationships and endocrine disruptors: a qualitative method of assessment.
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非单调剂量反应关系和内分泌破坏者：一种定性评估方法。
DOI：
10.1186/1476-069x-14-13
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发表时间：
2015-02-11
期刊：
影响因子：
--
通讯作者：
Rousselle C
中科院分区：
文献类型：
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作者：
Lagarde F;Beausoleil C;Belcher SM;Belzunces LP;Emond C;Guerbet M;Rousselle C
研究内分泌干扰物影响的实验研究经常发现潜在的非传统剂量-反应关系，称为非单调剂量-反应关系(NMDR)。缺乏在风险评估背景下调查NMDR关系的标准化方法。这项工作的目的是制定评估NMDR关系强度的标准。进行了文献检索，以确定报道NMDR与内分泌干扰物关系的已发表研究。选择了51项实验研究，这些研究调查了与许多物质引起的内分泌干扰有关的各种影响。评分标准适用于以前用于确定兴奋类型剂量-反应关系的方法。在分析的148个NMDR关系中，82个用这种方法被归类为对各种影响具有“中等”到“高度”可信水平。文献中描述的许多行动模式可以解释这种现象。NMDR可由多种分子机制引起，如不同亲和力的多个受体诱导的相反效应、受体脱敏、剂量增加的负反馈或剂量依赖的代谢调节。逐步决策树被开发为一种工具，用于标准化文献中观察到的NMDR关系的分析，最终目的是将这些结果用于风险评估目的。该决策树最终被应用于双酚A作用的研究。
Experimental studies investigating the effects of endocrine disruptors frequently identify potential unconventional dose-response relationships called non-monotonic dose-response (NMDR) relationships. Standardized approaches for investigating NMDR relationships in a risk assessment context are missing. The aim of this work was to develop criteria for assessing the strength of NMDR relationships. A literature search was conducted to identify published studies that report NMDR relationships with endocrine disruptors. Fifty-one experimental studies that investigated various effects associated with endocrine disruption elicited by many substances were selected. Scoring criteria were applied by adaptation of an approach previously used for identification of hormesis-type dose-response relationships. Out of the 148 NMDR relationships analyzed, 82 were categorized with this method as having a “moderate” to “high” level of plausibility for various effects. Numerous modes of action described in the literature can explain such phenomena. NMDR can arise from numerous molecular mechanisms such as opposing effects induced by multiple receptors differing by their affinity, receptor desensitization, negative feedback with increasing dose, or dose-dependent metabolism modulation. A stepwise decision tree was developed as a tool to standardize the analysis of NMDR relationships observed in the literature with the final aim to use these results in a Risk Assessment purpose. This decision tree was finally applied to studies focused on the effects of bisphenol A.