Biomonitoring Equivalents for bisphenol A (BPA)

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Abstract

Recent efforts worldwide have resulted in a growing database of measured concentrations of chemicals in blood and urine samples taken from the general population. However, few tools exist to assist in the interpretation of the measured values in a health risk context. Biomonitoring Equivalents (BEs) are defined as the concentration or range of concentrations of a chemical or its metabolite in a biological medium (blood, urine, or other medium) that is consistent with an existing health-based exposure guideline. BE values are derived by integrating available data on pharmacokinetics with existing chemical risk assessments. This study reviews available health-based exposure guidance values for bisphenol A (BPA) from Health Canada, the United States Environmental Protection Agency (USEPA) and the European Food Safety Authority (EFSA). BE values were derived based on data on BPA urinary excretion in humans. The BE value corresponding to the oral provisional tolerable daily intake (pTDI) of 25 μg/kg-d from Health Canada is 1 mg/L (1.3 mg/g creatinine); value corresponding to the US EPA reference dose (RfD) and EFSA tolerable daily intake (TDI) estimates (both of which are equal to 50 μg/kg-d) is 2 mg/L (2.6 mg/g creatinine). These values are estimates of the 24-h average urinary BPA concentrations that are consistent with steady-state exposure at the respective exposure guidance values. These BE values may be used as screening tools for evaluation of central tendency measures of population biomonitoring data for BPA in a risk assessment context and can assist in prioritization of the potential need for additional risk assessment efforts for BPA relative to other chemicals.

Introduction

Interpretation of measurements of concentrations of chemicals in samples of urine or blood from individuals in the general population is hampered by the general lack of screening criteria for evaluation of such biomonitoring data in a health risk context. Without such screening criteria, biomonitoring data can be interpreted in terms of exposure trends, but cannot be used to evaluate which chemicals may be of concern in the context of current risk assessments. Such screening criteria would ideally be based on robust datasets relating potential adverse effects to biomarker concentrations in human populations (see, for example, the U.S. Centers for Disease Control and Prevention (CDC) blood lead level of concern; see http://www.cdc.gov/nceh/lead/). However, development of such epidemiologically-based screening criteria is a resource and time-intensive effort. As an interim approach, the development of Biomonitoring Equivalents (BEs) has been proposed, and guidelines for the derivation and communication of these values have been developed (Hays et al., 2008, 2007; LaKind et al., 2008). Such an interpretive tool, in the form of biological exposure indices (BEIs), has been developed by the ACGIH for a number of chemicals (e.g., ACGIH, 2007).

A BE is defined as the concentration or range of concentrations of chemical in a biological medium (blood, urine, or other medium) that is consistent with an existing health-based exposure guidance value such as a reference dose (RfD) or tolerable daily intake (TDI). Its estimation is based on existing chemical-specific pharmacokinetic data (animal or human) and the point of departure (POD) used in the derivation of an exposure guidance value (such as the RfD or TDI) (Hays et al., 2008). BEs should be used as screening tools to allow an assessment of biomonitoring data to evaluate which chemicals have large, small, or no margins of safety compared to existing risk assessments and exposure guidance values. Robustness of a BE value relies on the underlying exposure guidance values and pharmacokinetic data used to derive it.

This document presents derivation of BE values for 2,2-bis(4-hydroxyphenyl)propane, also known as bisphenol A (BPA; Chemical Abstracts Services [CAS] Registry number 80-05-7). BPA is a monomer used in the production of polycarbonate (PC) plastics and epoxy-phenolic resins. Polycarbonates are used extensively in food containers: e.g. water bottles, plates, and mugs. Epoxy-phenolic resins are used as an internal, protective lining or coating of cans for foods and beverages (Health Canada, 2008, EFSA, 2006). Because of its wide use in food packaging and food containers, BPA has the potential to leach into foods, and widespread exposure to low levels of BPA in the general population has been confirmed through biomonitoring studies (Dekant and Völkel, 2008, Calafat et al., 2005, Calafat et al., 2008). Oral exposure is expected to be the predominant route of exposure because of the low vapor pressure of BPA and its use patterns (Dekant and Völkel, 2008).

Section snippets

Exposure guidance values, critical effects, and mode of action

BPA has been the subject of numerous risk assessment reviews, with increased attention over the last decade related to evaluating its potential for producing adverse health effects through an endocrine disruption mechanism (Health Canada, 2008, EFSA, 2006, EFSA, 2008, CERHR, 2008). Table 1 presents the available guidance values derived for BPA. In each case, the POD, the toxicological endpoint of interest, and the applied uncertainty factors are identified. The provisional tolerable daily

Sources of variability and uncertainty

The BE derived in this document relates to the total BPA in urine and was based on the human data of Völkel et al., 2002, Völkel et al., 2005. These data and thus the calculated BE values correspond to the total BPA in urine – which reflects the sum total of free BPA and BPA-G. The free BPA in urine would appear to be very low (less than 2% of applied dose) and probably unlikely to be quantitated in a reproducible manner.

One of the sources of variability and uncertainty associated with the BE

Conflict of Interest Statement

The authors declare they have no conflicts of interest.

Acknowledgments

Funding for this project was provided under a grant from Health Canada. The views expressed are those of the authors and do not necessarily reflect the views or policies of Health Canada. This BE dossier has undergone an independent peer-review to assure the methods employed here are consistent with the guidelines for derivation (Hays et al., 2008) and communication (LaKind et al., 2008) of Biomonitoring Equivalents and that the best available chemical-specific data was used in calculating the

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