Reconstructing Human Exposures Using Biomarkers and other “Clues”

Abstract

Biomonitoring is the process by which biomarkers are measured in human tissues and specimens to evaluate exposures. Given the growing number of population-based biomonitoring surveys, there is now an escalated interest in using biomarker data to reconstruct exposures for supporting risk assessment and risk management. While detection of biomarkers is de facto evidence of exposure and absorption, biomarker data cannot be used to reconstruct exposure unless other information is available to establish the external exposure–biomarker concentration relationship. In this review, the process of using biomarker data and other information to reconstruct human exposures is examined. Information that is essential to the exposure reconstruction process includes (1) the type of biomarker based on its origin (e.g., endogenous vs. exogenous), (2) the purpose/design of the biomonitoring study (e.g., occupational monitoring), (3) exposure information (including product/chemical use scenarios and reasons for expected contact, the physicochemical properties of the chemical and nature of the residues, and likely exposure scenarios), and (4) an understanding of the biological system and mechanisms of clearance. This review also presents the use of exposure modeling, pharmacokinetic modeling, and molecular modeling to assist in integrating these various types of information.

Acknowledgments

The U.S. Environmental Protection Agency through its Office of Research and Development funded and managed the research described here. It has been subjected to the agency's administrative review and approved for publication. The authors thank Drs. Jeffre Johnson and Hisham El-Masri from the U.S. Environmental Protection Agency for their detailed review of the draft article.

Notes

This article is not subject to U.S. copyright.

¹MOE (Molecular Operating Environment) is a software package developed by Chemical Computing Group, Inc. It contains Structure-Based Design; Pharmacophore Discovery; Protein & Antibody Modeling; Molecular Modeling & Simulations; Cheminformatics & (HTS) QSAR; and Medicinal Chemistry Applications.

²QikProp is a product from Schrõdinger, LLC (https://www.schrodinger.com/products/14/17). It can be used to predict parameters such as octanol/water and water/gas log P, logs, log BB, overall central nervous system (CNS) activity, Caco-2 and MDCK cell permeabilities, human oral absorption, log K _hsa for human serum albumin binding, and log IC₅₀ for HERG K⁺-channel blockage.

³OEChem, version 1.7.4, OpenEye Scientific Software, Inc., Santa Fe, NM, www.eyesopen.com, 2010.

⁴CoMFA (Comparative Molecular Field Analysis) is a 3D QSAR technique based on data from known active molecules. The aim of CoMFA is to derive a correlation between the biological activity of a set of molecules and their 3D shape and electrostatic and hydrogen bonding characteristics. See http://www.cmbi.ru.nl/edu/bioinf4/comfa-Prac/comfa.shtml