Diurnal variability in urinary volatile organic compound metabolites and its association with oxidative stress biomarkers

Volatile organic compounds (VOCs) are ubiquitous environmental pollutants that are associated with birth defects, leukemia, neurocognitive deficits, reproductive impairment and cancer in humans exposed to these compounds. Exposure to VOCs can be assessed by measuring their metabolites in urine. Little is known, however, about the temporal variability in urinary VOC metabolite (VOCM) concentrations within- and between-individuals. In this study, we determined the variability in the concentrations of 38 VOCMs in urine samples collected from 19 healthy individuals across a period of 44 days. We also measured seven biomarkers of oxidative stress (lipid, protein and DNA damage) in urine to assess the relationship of VOC exposure to oxidative stress. Seventeen VOCMs had detection frequencies (DFs) of >60% in urine, and we limited further data analysis to those compounds. The creatinine-adjusted geometric mean concentrations of VOCMs ranged from 2.70 μg/g to 327 μg/g in spot and 2.60 μg/g to 551 μg/g in first morning void (FMV) urine samples. Calculation of the intra-class correlation coefficients (ICCs) for 17 VOCM concentrations to assess their predictability and repeatability in urinary measurements showed ranges of 0.080-0.425 in spot and 0.050-0.749 in FMV urine samples, revealing notable within-individual variability. Our results suggest that taking only single measurements of VOCM concentrations in urine in epidemiological investigations may lead to exposure misclassification. In addition, VOCM concentrations were significantly and positively correlated with oxidative stress biomarkers. This study thus provides important information for formulating sampling strategies in the biomonitoring of VOC exposure in human populations.