Evaluation of Biomonitoring Equivalents for Benzene Risk Assessment: an Environmental-Wide Association Study Approach

Abstract

A biomonitoring equivalent (BE) is the concentration of a chemical or its metabolite in a biological matrix. The BE is estimated from an existing exposure guidance value such as a reference dose (RfD). An environmental-wide association study (EWAS) provides an epidemiologic screening tool to simultaneously evaluate multiple health outcomes for potential association with an exposure. We evaluated over 120 health outcomes, including self-reported medical and disease conditions and blood chemistry parameters, for potential associations with blood benzene level. The study population included adults who participated in the 2003-04 and 2005-06 waves of the National Health and Nutrition Examination Survey. Logistic regression models of benzene classified as above or below the BE were adjusted for age, sex, race, smoking, and socioeconomic status. Odds ratios (OR) estimated the association between each health outcome for an elevated BE relative to a concentration below the BE. More than 1,300 adults with blood benzene concentration were included. The proportion with a blood benzene level exceeding the BE value was 12%. Blood benzene level was positively associated with an elevated serum cotinine level indicative of current cigarette smoking (OR=1.03, p<0.01). Among current smokers, having a blood benzene level above the BE was associated with elevated white blood cell count (OR=1.1, p<0.05), hemoglobin (OR=1.3, p<0.01), hematocrit (OR=1.1, p=0.01), and albumin (OR=2.3, p=0.03), and decreased blood urea nitrogen (OR=0.9, p<0.01) and alpha-carotene (OR=0.8, p<0.01). We observed significant associations between elevated blood benzene level and several clinical biochemistry parameters. Biomarker concentrations expressed as BE values allow for evaluation of health risks using population-based biomonitoring data. The EWAS approach can assess the distribution of risks for a range of health outcomes in a general population for exposure levels relative to an RfD.