Lead neurotoxicity in children: Decomposing the variability in dose-effect relationships
Lead neurotoxicity in children: Decomposing the variability in dose-effect relationships
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DOI：
10.1002/ajim.20438
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发表时间：
2007-10-01
影响因子：
3.5
通讯作者：
Bellinger, David C.
中科院分区：
文献类型：
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作者：
Bellinger, David C.
背景近几十年来，我们对儿童铅神经毒理学的认识取得了巨大进展，但进一步进展的一个重要障碍是铅生物标志物与健康终点之间的显著差异。（2）不完全表征的终点方差归因于其他因素比铅;（3）个体间差异的易感性铅neurotoxicity.Results的策略，建议减少这些来源，包括开发有效的PBPK模型和生物标志物的早期生物学效应的变异贡献;开发更全面的结果差异模型，特别是应用包含超个人和超家庭风险因素的多层次模型;和使用的研究设计，允许评估的影响修改的影响，背景因素的形式和严重程度的神经toxication. ConclusionDecomposing的变异性分布的观察分数周围的最好的，描述儿童铅神经毒性的剂量效应关系的拟合线是一个主要的研究需求。
Background Enormous progress has been made in recent decades in our understanding of lead neurotoxicology in children, but an important obstacle to additional progress is the striking variability that is evident in any plot of a lead biomarker versus a health endpoint.Methods In this article, three potential sources of variability are identified: (1) errors or imprecision in characterizing dose (and/or outcome); (2) incomplete characterization of endpoint variance attributable to factors other than lead; and (3) inter-individual differences in susceptibility to lead neurotoxicity.Results Strategies are suggested for reducing the variability contributed by these sources, including the development of validated PBPK models and biomarkers of early biological effects; the development of more comprehensive models of outcome variance and, specifically, the application of multi-level models that incorporate supra-individual and supra-family risk factors; and the use of study designs that permit assessments of the effect modifying influence of contextual factors on the form and severity of neurotoxicity.Conclusion Decomposing the variability in the distribution of observed scores around the best-fit lines that describe the dose-effect relationships for lead neurotoxicity in children is a major research need.