Assessing the accuracy of exposure measurements for common endocrine disrupting chemicals

项目总结 我们支持收集和分析人类胎儿卵巢的十年计划突然被取消 四年前停止了，因为我们队列中的一些母亲尿样中含有高水平的BPA 引起了人们对我们分析能力的怀疑。我们获得了一年的R56资金，并使用了它 为了验证我们新的直接分析方法的准确性，并证明旧的间接分析方法 人类对双酚A暴露的估计所基于的方法不能准确地捕捉到 主要的BPA代谢物BPA-葡萄糖醛酸(BPA-G)水平。我们的数据显示人类双酚A 风险敞口被严重低估了。此外，由于葡萄糖醛酸化的代谢物 我们的发现是用类似的间接方法测量其他内分泌干扰物 让人担心这可能是一个普遍存在的问题。拟议的试点研究开始解决 这种关注集中在三种化学物质上，这三种化学物质代表三种不同的内分泌 破坏化学物质。我们将制定直接的方法，使用真实的专业标准 三种化学物质的代谢产物，并使用这些方法来评估当前 使用间接方法测量人类生物标本中的它们。我们假设，就像双酚A一样， 我们将在间接分析中发现至少三个中的两个是不准确的。因为人类 生物监测数据被用来获得对人类暴露的估计，这些估计又反过来， 在安全评估中是必不可少的，拟议的研究不仅可能影响 旨在评估这些化学物质对人类的影响的人类流行病学研究 健康，也颠覆了化学风险评估。

PROJECT SUMMARY Our ten-year project supporting the collection and analysis of human fetal ovaries was abruptly halted four years ago when high levels of BPA in some maternal urine samples in our cohort raised suspicion about our analytical prowess. We secured one year of R56 funding and used it to verify the accuracy of our new direct analytical method and demonstrate that older indirect methods on which human estimates of BPA exposure have been based do not accurately capture levels of the major BPA metabolite, BPA-glucuronide (BPA-G). Our data suggest human BPA exposure has been significantly underestimated. Further, because glucuronidated metabolites of other endocrine disrupting chemicals are measured using similar indirect methods, our findings raise concern that this may be a pervasive problem. The proposed pilot studies begin to address this concern by focusing on three chemicals that represent three different classes of endocrine disrupting chemicals. We will develop direct methods using authentic standards for the major metabolites of the three chemicals and use these methods to assess the accuracy of currently used indirect methods for measuring them in human biospecimens. We postulate that, like BPA, we will find inaccuracies in indirect analyses for at least two of the three. Because human biomonitoring data are used to obtain estimates of human exposure and these estimates, in turn, are essential in safety assessments, the proposed studies have the potential to affect not only human epidemiological studies designed to assess the effects of these chemicals on human health, but also to upend chemical risk assessment.