Abstract
BackgroundBecause some adverse health effects associated with chronic arsenic exposure may be mediated by methylated arsenicals, interindividual variation in capacity to convert inorganic arsenic into mono- and di-methylated metabolites may be an important determinant of risk associated with exposure to this metalloid. Hence, identifying biological and behavioral factors that modify an individual’s capacity to methylate inorganic arsenic could provide insights into critical dose-response relations underlying adverse health effects.MethodsA total of 904 older adults (≥45 years old) in Churchill County, Nevada, who chronically used home tap water supplies containing up to 1850 μg of arsenic per liter provided urine and toenail samples for determination of total and speciated arsenic levels. Effects of biological factors (gender, age, body mass index) and behavioral factors (smoking, recent fish or shellfish consumption) on patterns of arsenicals in urine were evaluated with bivariate analyses and multivariate regression models.ResultsRelative contributions of inorganic, mono-, and di-methylated arsenic to total speciated arsenic in urine were unchanged over the range of concentrations of arsenic in home tap water supplies used by study participants. Gender predicted both absolute and relative amounts of arsenicals in urine. Age predicted levels of inorganic arsenic in urine and body mass index predicted relative levels of mono- and di-methylated arsenic in urine. Smoking predicted both absolute and relative levels of arsenicals in urine. Multivariate regression models were developed for both absolute and relative levels of arsenicals in urine. Concentration of arsenic in home tap water and estimated water consumption were strongly predictive of levels of arsenicals in urine as were smoking, body mass index, and gender. Relative contributions of arsenicals to urinary arsenic were not consistently predicted by concentrations of arsenic in drinking water supplies but were more consistently predicted by gender, body mass index, age, and smoking.ConclusionsThese findings suggest that analyses of dose-response relations in arsenic-exposed populations should account for biological and behavioral factors that modify levels of inorganic and methylated arsenicals in urine. Evidence of significant effects of these factors on arsenic metabolism may also support mode of action studies in appropriate experimental models.Electronic supplementary materialThe online version of this article (doi:10.1186/s12940-016-0144-x) contains supplementary material, which is available to authorized users.
Highlights
Because some adverse health effects associated with chronic arsenic exposure may be mediated by methylated arsenicals, interindividual variation in capacity to convert inorganic arsenic into mono- and di-methylated metabolites may be an important determinant of risk associated with exposure to this metalloid
These analyses found that all biological factors and a behavioral factor, smoking behavior, significantly affected absolute or relative levels of inorganic arsenic (iAs) or its methylated metabolites in urine
Increasing home tap water total arsenic in home tap water (TAs) concentrations were significantly associated with increasing urinary sum of iAsIII and iAsV (TiAs), MMA, and DMA concentrations
Summary
Because some adverse health effects associated with chronic arsenic exposure may be mediated by methylated arsenicals, interindividual variation in capacity to convert inorganic arsenic into mono- and di-methylated metabolites may be an important determinant of risk associated with exposure to this metalloid. In a study population of older adults from Churchill County, Nevada, we have previously examined relations between dose (measured by the total arsenic (TAs) concentration in home tap water) and response (measured as summed urinary concentrations of speciated arsenicals) and modification of these relations by both biological (e.g., gender) and behavioral (e.g., smoking) factors [1]. Informative, this analysis did not directly examine dose-response relations for individual urinary metabolites of inorganic arsenic (iAs) or effects of modifying factors on urinary levels of iAs and its monomethylated (MMA) and dimethylated (DMA) metabolites. Characterizing effects of biological and behavioral factors on these doseresponse relations may clarify their contributions to interindividual variation in capacity to convert iAs into methylated metabolites
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