Department of Biostatistics, University of Copenhagen, Denmark.
Risk Anal. 2013 Mar;33(3):450-61. doi: 10.1111/j.1539-6924.2012.01882.x. Epub 2012 Aug 24.
Lead is a recognized neurotoxicant, but estimating effects at the lowest measurable levels is difficult. An international pooled analysis of data from seven cohort studies reported an inverse and supra-linear relationship between blood lead concentrations and IQ scores in children. The lack of a clear threshold presents a challenge to the identification of an acceptable level of exposure. The benchmark dose (BMD) is defined as the dose that leads to a specific known loss. As an alternative to elusive thresholds, the BMD is being used increasingly by regulatory authorities. Using the pooled data, this article presents BMD results and applies different statistical techniques in the analysis of multistudy data. The calculations showed only a limited variation between studies in the steepness of the dose-response functions. BMD results were quite robust to modeling assumptions with the best fitting models yielding lower confidence limits (BMDLs) of about 0.1-1.0 μ g/dL for the dose leading to a loss of one IQ point. We conclude that current allowable blood lead concentrations need to be lowered and further prevention efforts are needed to protect children from lead toxicity.
铅是一种公认的神经毒素，但要估算可测量的最低水平的影响是很困难的。一项来自七个队列研究的国际综合数据分析报告称，儿童血液铅浓度与智商分数之间呈反比和超线性关系。缺乏明确的阈值给确定可接受的暴露水平带来了挑战。基准剂量（BMD）定义为导致特定已知损失的剂量。作为难以捉摸的阈值的替代方法，监管机构越来越多地使用 BMD。本文使用综合数据，提供了 BMD 结果，并在多研究数据分析中应用了不同的统计技术。计算结果表明，在剂量反应函数的陡峭程度上，各研究之间只有有限的差异。BMD 结果对模型假设非常稳健，最佳拟合模型产生的置信下限（BMDL）约为 0.1-1.0μg/dL，对应于导致智商损失一个点的剂量。我们得出结论，目前允许的血铅浓度需要降低，需要进一步采取预防措施，以保护儿童免受铅毒性的侵害。
