Total imprecision of exposure biomarkers: Implications for calculating exposure limits
Total imprecision of exposure biomarkers: Implications for calculating exposure limits
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DOI：
10.1002/ajim.20474
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发表时间：
2007-10-01
影响因子：
3.5
通讯作者：
Buclu-Jorgensen, Esben
中科院分区：
文献类型：
--
作者：
Grandjean, Philippe;Buclu-Jorgensen, Esben
背景暴露生物标志物的不精确度评估通常只侧重于实验室表现。无法识别的不精确导致低估了接触的真正毒性。我们评估了暴露生物标志物的总不精确度及其对暴露限度计算的影响。方法在出生队列研究中，脐带血、脐带组织和母亲头发中的汞浓度被用作产前甲基汞暴露的生物标志物。我们确定了它们之间的相互关系，以及它们与孩子7岁时神经行为结果变量的关系。在至少有3个暴露参数的情况下，可以使用因子分析和结构方程模型来确定每个生物标志物的总不精确度，然后利用估计的不精确度来调整基准剂量计算和导出的暴露限值。结果暴露生物标志物之间有很好的相关性，但脐带血汞浓度与神经行为缺陷的相关性最好。因子分析和结构方程模型显示，脐带血参数的总不精确度为25%-30%，母亲头发的总不精确度几乎是这些不精确度的两倍，这些不精确度导致基准剂量水平膨胀。调整后的计算结果表明，接触限值比美国国家研究委员会推荐的水平低50%。结论生物标记物25%-50%的不精确度远远超过正常的实验室变异性。这种不精确导致低估了与剂量有关的毒性，因此在数据分析和得出暴露限值时必须加以考虑。未来的研究理想情况下应该包括至少三个暴露参数，以允许对完全不精确的独立评估。
Background Assessment of the imprecision of exposure biomarkers usually focuses on laboratory performance only. Unrecognized imprecision leads to underestimation of the true toxicity of the exposure. We have assessed the total imprecision of exposure biomarkers and the implications for calculation of exposure limits.Methods In a birth cohort study, mercury concentrations in cord blood, cord tissue, and maternal hair were used as biomarkers of prenatal methylmercury exposure. We determined their mutual correlations and their associations with the child's neurobehavioral outcome variables at age 7 years. With at least three exposure parameters available, factor analysis and structural equation modeling could be applied to determine the total imprecision of each biomarker The estimated imprecision was then applied to adjust benchmark dose calculations and the derived exposure limits.Results The exposure biomarkers correlated well with one another, but the cord blood mercury concentration showed the best associations with neurobehavioral deficits. Factor analysis and structural equation models showed a total imprecision of the cord-blood parameter of 25-30%, and almost twice as much for maternal hair These imprecisions led to inflated benchmark dose levels. Adjusted calculations resulted in an exposure limit 50% below the level recommended by the U.S. National Research Council.Conclusions The biomarker imprecisions of 25-50% much exceeded normal laboratory variability. Such imprecision causes underestimation of dose-related toxicity and therefore must be considered in the data analysis and when deriving exposure limits. Future studies should ideally include at least three exposure parameters to allow independent assessment of total imprecision.