Article

Using Biomonitoring Equivalents to interpret human biomonitoring data in a public health risk context

Summit Toxicology, LLP, 165 Valley Road, Lyons, CO 80540, USA.
Journal of Applied Toxicology (Impact Factor: 3.17). 05/2009; 29(4):275-88. DOI: 10.1002/jat.1410
Source: PubMed

ABSTRACT Increasingly sensitive analytical tools allow measurement of trace concentrations of chemicals in human biological media in persons from the general population. Such data are being generated by biomonitoring programs conducted by the US Centers for Disease Control and other researchers. However, few screening tools are available for interpretation of such data in a health risk assessment context. This review 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 or reference dose. 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 four case study chemicals (toluene, 2,4-dichlorophenoxyacetic acid, cadmium and acrylamide) are presented, and the interpretation of biomonitoring data for these chemicals is presented using the BE values. These case studies demonstrate that a range of pharmacokinetic data and approaches can be used to derive BE values; fully developed physiologically based pharmacokinetic models, while useful, are not required. The resulting screening level evaluation can be used to classify these compounds into relative categories of low, medium and high priority for risk assessment follow-up. Future challenges related to the derivation and use of BE values as tools in risk management are discussed.

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Available from: Sean M Hays, Aug 28, 2015
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    • "At present, human exposure assessment is based largely on measured levels of environmental agents in the human environment (U.S. EPA 2010); in some cases, internal dose measures may also be obtained using biomonitoring (Hays and Aylward 2008) or pharmacokinetic modeling (Barton et al. 2007). In the NexGen approach, exposure assessment will focus more on direct measures of critical toxicity pathway perturbations in humans using advanced biomonitoring techniques (NRC 2012) coupled with innovative new high throughput approaches to obtaining indicators of exposure to large numbers of environmental agents simultaneously (Jones et al. 2012). "
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    • "The BE is defined as the concentration of a chemical or metabolite in a biological medium (blood, urine, human milk, etc.) that is consistent with an existing exposure guidance value such as a tolerable daily intake (TDI) or reference dose (RfD). Subsequently, the BE approach has been extensively refined and expanded (reviewed in Becker et al., 2012; Hays & Aylward, 2009), and BE values have been derived for approximately 80 chemicals, including persistent organic compounds (e.g. dioxins, hexachlorobenzene, and DDT), approximately 40 volatile organic compounds, phthalates and phenols (bisphenol A, triclosan and several phthalates), certain pyrethroid pesticides, and for selected brominated flame retardant compounds (Angerer et al., 2011).Scientists from the private sector, CDC/ATSDR and US EPA have recently collaborated to compare BEs to measured biomarker concentrations for approximately 130 substances in the CDC’s National Exposure Report to provide a risk assessment perspective on the significance of the levels of these substances found in the US population (Aylward et al., 2013). "
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    • "The report by the National Research Council ''Toxicity Testing in the 21st Century'' (NRC, 2007) has spawned multiple research efforts in the United States and Europe aimed toward use of in vitro HTS assays in the toxicological assessment of environmental chemicals (Abbott, 2009; Kavlock et al., 2009; Knight, 2008). However, meaningful incorporation of these in vitro findings into such an assessment is dependent upon adequate consideration of in vivo pharmacokinetics to determine the relevance of these data to the external and internal doses achieved during human exposure scenarios (Blaauboer, 2010; Hays and Aylward, 2009). Within the pharmaceutical industry, IVIVE modeling approaches have been widely used to assess the preclinical pharmacokinetics of candidate molecules (Caldwell et al., 2009; De Buck and Mackie, 2007). "
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