Invited Commentary: Exposure Biomarkers Indicate More Than Just Exposure

Biomarkers of environmental exposures have notable strengths in integrating information across diverse sources and routes of exposure and providing a marker reflecting biological dose. However, the physiological determinants of biomarker toxicokinetics and measured levels may also affect or be affected by disease determinants and thus introduce confounding. In a study published in this issue of the Journal, Sagiv et al. (Am J Epidemiol. 2018;187(4):793-802) sought empirical evidence on the role of renal clearance in biasing the association between perfluoroalkyl compounds measured in plasma during pregnancy and infant birth weight. They found little empirical support for such bias. The risk of such bias is greater when the exposure and health outcome are assessed closely in time, when physiological differences are large relative to variability in environmental levels, and when the physiological determinant has diverse functions and implications. While empirical examination has value, the potential bias is difficult to measure and control when the underlying associations among exposure biomarker, health outcome, and physiological determinant are weak.