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Effects of biological and behavioral factors on urinary arsenic metabolic profiles in a U.S. population
Citation:
Hudgens, E., Z. Drobna, B. He, X. Le, M. Styblo, J. Rogers, AND D. Thomas. Effects of biological and behavioral factors on urinary arsenic metabolic profiles in a U.S. population. ENVIRONMENTAL HEALTH. Academic Press Incorporated, Orlando, FL, 15(1):62, (2016).
Impact/Purpose:
This manuscript reports unique dose-response data for a U.S. population chronically exposed to inorganic arsenic and on the modifying effects of biological and behavioral factors on metabolism. This information addresses concerns of risk assessors about the sources of interindividual variability and the need for its consideration in regulatory decisions.
Description:
Abstract In older men and women who were long-term residents of Churchill County, Nevada, we examined the relation between arsenic exposure from home tap water and urinary levels of inorganic arsenic and its methylated metabolites. Over a wide exposure range (up to 1850 ug of arsenic per liter), urinary concentrations of inorganic, monomethylated, and dimethylated arsenicals strongly correlated with home tap water arsenic concentrations. However, percentages of summed urinary concentrations of inorganic, monomethylated, and dimethylated arsenicals accounted for by each arsenical species were unaffected by arsenic concentration in home tap water, suggesting thc1t capacity for formation and excretion of methylated metabolites was not exceeded. Biological factors (gender, age, body mass index, and genotype) and a behavioral factor (smoking) influenced absolute and relative levels of arsenicals in urine. A multivariate regression model showed that both biological and behavioral factors were significant predictors of absolute and relative concentrations of inorganic arsenic and its methylated metabolites in urine. These findings suggest that analyses of dose-response relations in arsenic-exposed populations should account for these biological and behavioral factors. Furthermore, evidence of significant effects of these factors on arsenic metabolism may support mode of action studies in appropriate experimental models. Running title- Methylated arsenicals as urinary biomarkers in a U.S. population Funding sources- This research was supported by the Office of Research and Development, U.S. Environmental Protection Agency. Abbreviations (in order of occurrence)- iAs, inorganic arsenic; MMA, monornethylated arsenic; DMA, dimethylated arsenic: TAs, total arsenic in home tap water; LOD, limit of detection; BMI, body mass index; AS3MT, arsenic (+3 oxidation state) methyltransferase; MCL, maximum contaminant level; iAs111, arsenite; MAsv, monomethylarsonic acid; iAsv, arsenate; DMAsv, dimethylarsinic acid; TiAs, sum of iAs111 and iAsv; USAs, sum ofTiAs, MMA, and DMA; PMI, primary methylation indE!x; SMI, secondary methylation index; SNP, single nucleotide polymorphism; VNTR, variable number tandem repeat Protection of human participants- As noted in Section 2.2., the study protocol was approved by the Institutional Review Board of the University of North Carolina at Chapel Hill and reviewed by the Human Subjects Protection Office of the U.S. EPA. All participants provided written consent. Oversight provided by these bodies is consistent with national and international standards for the conduct of research in humans.
