Application of Urinary Arsenic Metabolites to Assess Arsenic Exposure in Southeastern Michigan: Advancing Exposure Assessment for Epidemiology Research.

Abstract

Urinary arsenic metabolites are used in epidemiological studies to assess arsenic exposure. However, to ensure reliable application of the biomarker, further development is needed. This research contributes to the validation of urinary arsenic metabolites as arsenic exposure biomarkers in a subsample of 167 bladder cancer cases and 254 controls enrolled in a large case-control study in Southeastern Michigan. This work aims to develop an analytical protocol to speciate arsenic metabolites in urine, assess the reliability of sampling strategies, the exposure-biomarker relationship, and the relationship between the biomarker and disease. Information on demographics, smoking, dietary intake and drinking water intake was collected from participants. Urine samples were speciated using an HPLC-ICPMS coupled-system. Six species were measured As[III], As[V], DMA[V], MMA[V], MMA[III], and Arsenobetaine. The sum of As[III], As[V], MMA[V], and DMA[V] was designated total arsenic (TotAs). A subpopulation (n=131) provided additional urine samples to compare the arsenic levels in spot and first morning void (FMV) samples. The interclass correlation coefficient between TotAs in FMV and TotAs in spot samples showed that 90% of variation comes from between individuals and not within individuals. Drinking water arsenic concentration was a significant predictor (p<0.0001) of TotAs (R2=0.17). The correlation increased to 0.24 (p<0.0001) and 0.39 (p<0.0001) when the exposure was categorized by arsenic concentrations in water (≥1µg/L) and water intake (above and below median), respectively. Significant associations between TotAs and bladder cancer suggest that individuals who ingest elevated levels of arsenic may retain the metalloid in their bodies. However, sample size limitations and study design have to be considered when evaluating these associations. These results indicate that urinary arsenic metabolites can be used as biomarkers to assess recent arsenic intake via drinking water. Categorical estimates of water consumption better characterize intake in this population. Selection of adequate exposure measures may reduce misclassification in self-reported water consumption. FMV and spot samples can be used without preference when evaluating arsenic exposure in epidemiological studies. These results advance the validation process of urinary arsenic metabolites as biomarkers of arsenic exposure which are essential tools in risk assessment and epidemiological studies.