Assessing the accuracy of exposure measurements for common endocrine disrupting chemicals

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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.