Assessing the accuracy of exposure measurements for common endocrine disrupting chemicals

项目摘要 我们支持收集和分析人类胎儿卵巢的十年计划突然中断了。 四年前，当我们的队列中一些孕妇尿液样本中的BPA含量过高时， 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， 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 人类估计BPA暴露的方法并不能准确地捕捉到 BPA的主要代谢物BPA-葡糖苷酸（BPA-G）的水平。我们的数据表明人类双酚A 风险被严重低估。此外，由于葡萄糖醛酸化代谢物 我们的研究结果表明，其他内分泌干扰化学品也是用类似的间接方法测量的。 令人担忧的是，这可能是一个普遍的问题。拟议的试点研究开始， 通过关注代表三种不同类型内分泌的三种化学物质， 破坏化学物质。我们将开发使用真实标准的直接方法， 三种化学物质的代谢产物，并使用这些方法来评估目前的准确性 使用间接方法测量人体生物标本中的它们。我们假设，就像BPA一样， 我们会发现间接分析中至少有两个不准确。因为人类 生物监测数据被用于获得人类接触的估计值，而这些估计值反过来， 在安全性评估中至关重要，拟议的研究不仅可能影响 人类流行病学研究，旨在评估这些化学品对人类的影响 健康，而且还颠覆了化学品风险评估。

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.