Development and Application of Biomonitoring Equivalents for Interpreting Biomonitoring Data in a Human Health Risk Context

Abstract

Increasingly sensitive analytical tools allow measurement of trace concentrations of chemicals in human biologic media in persons from the general population. Such data are being generated by biomonitoring programs conducted by the U.S. Centers for Disease Control (CDC), the European Union, Canada and other regional and national governments and other researchers. However, few screening tools are available for interpretation of such data in a health risk assessment context. This dissertation describes the concept and implementation of Biomonitoring Equivalents (BEs), estimates of the concentration of a chemical or metabolite in a biological medium that is consistent with an existing exposure guidance value such as a tolerable daily intake (TDI) or reference dose (RfD). The BE approach integrates available pharmacokinetic data to convert an existing exposure guidance value into an equivalent concentration in a biological medium. Key concepts regarding the derivation and communication of BE values resulting from an expert workshop held in 2007 are summarized. BE derivations for a series of compounds are presented: toluene, 2,4-dichlorophenoxyacetic acid (2,4-D), cadmium, acrylamide, trihalomethanes (chloroform, bromoform, chlorodibromomethane, dichlorobromomethane), and cyfluthrin. The interpretation of biomonitoring data for 2,4-D and the trihalomethanes using the BE values are presented. These case studies demonstrate that a range of pharmacokinetic data and approaches can be used to derive BE values; fully-developed physiologically based pharmacokinetic (PBPK) models, while useful, are not required. Often, data from simple controlled dosing studies in humans prove the most useful for derivation of BEs. Comparing biomonitoring data with the BE provides the risk manager a means of assessing the priority for risk assessment follow-up required for a chemical. The communication model for interpreting biomonitoring data in the context of the BE relies on classifying compounds in relative priority for risk assessment follow-up, where risk assessment follow-up may include; exposure assessment evaluations, re-evaluating the underlying risk assessments, and risk management or product stewardship actions. Biomonitoring data for some compounds may be orders of magnitude below the BEs, while biomonitoring levels for other compounds may approach or exceed the chemical-specific BEs. Using conventional risk assessment approaches, the ratio between the BE and biomonitoring levels can be regarded as a margin of safety. The compounds with the lowest margin of safety would indicate a higher priority for risk management efforts. Comparing biomonitoring results from the CDC to the available BEs indicate a relative margins of safety of (from highest to lowest) cyfluthrin, toluene, 2,4-D, trihalomethanes, cadmium and acrylamide. Therefore, prioritization for risk assessment follow-up would be (from lowest priority to highest priority): cyfluthrin, toluene, 2,4-D, cadmium, trihalomethanes and acrylamide. Biomonitoring has been called the ‘gold standard’ of exposure assessment. However, it is only with quantitative tools like the BE, which allow interpretation of biomonitoring data in a risk assessment context, that biomonitoring data can be fully appreciated and then become the ‘gold standard’ of exposure assessment and an important tool in human health risk assessment.