title: Biological and behavioral factors modify urinary arsenic metabolic profiles in a U.S. population.
abstract: 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. 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.
  
  
  
  A 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.
  
  
  
  Relative 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.
  
  
  
  These 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.
authors.affiliation: Environmental Public Health Division, National Health and Environmental Effects Research Laboratory, Office of Research and Development, U.S. Environmental Protection Agency, Research Triangle Park, NC, 27709, USA.
authors.forename: Edward E
authors.initials: EE
authors.lastname: Hudgens
authors.affiliation: Department of Nutrition, University of North Carolina at Chapel Hill, Chapel Hill, NC, 27599, USA.
authors.forename: Zuzana
authors.initials: Z
authors.lastname: Drobna
authors.affiliation: Analytical and Environmental Toxicology, Department of Laboratory Medicine and Pathology, Faculty of Medicine and Dentistry, University of Alberta, Edmonton, AB, T6G 2G3, Canada.
authors.forename: Bin
authors.initials: B
authors.lastname: He
authors.affiliation: Analytical and Environmental Toxicology, Department of Laboratory Medicine and Pathology, Faculty of Medicine and Dentistry, University of Alberta, Edmonton, AB, T6G 2G3, Canada.
authors.forename: X C
authors.initials: XC
authors.lastname: Le
authors.affiliation: Department of Nutrition, University of North Carolina at Chapel Hill, Chapel Hill, NC, 27599, USA.
authors.forename: Miroslav
authors.initials: M
authors.lastname: Styblo
authors.affiliation: Westat, 1600 Research Boulevard, Rockville, MD, 20850, USA.
authors.forename: John
authors.initials: J
authors.lastname: Rogers
authors.affiliation: Integrated Systems Toxicology Division, National Health and Environmental Effects Research Laboratory, Office of Research and Development, U.S. Environmental Protection Agency, Research Triangle Park, NC, 27709, USA. thomas.david@epa.gov.
authors.forename: David J
authors.initials: DJ
authors.lastname: Thomas
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000818:Animals; D001151:Arsenic / Q000032:analysis / Q000378:metabolism / Q000652:urine*; D001152:Arsenicals / Q000378:metabolism / Q000652:urine*; D003367:Cotinine / Q000652:urine; D003404:Creatinine / Q000652:urine; D004305:Dose-Response Relationship, Drug; D060766:Drinking Water / Q000032:analysis; D004781:Environmental Exposure / Q000032:analysis; D004785:Environmental Pollutants / Q000032:analysis / Q000378:metabolism / Q000652:urine*; D005260:Female; D005399:Fishes; D005506:Food Contamination; D006801:Humans; D008297:Male; D008875:Middle Aged; D009262:Nails / Q000737:chemistry; D009749:Nutrition Surveys; D012907:Smoking / Q000652:urine
chemical_list: D001152:Arsenicals; D060766:Drinking Water; D004785:Environmental Pollutants; D003404:Creatinine; D003367:Cotinine; D001151:Arsenic
keywords: BMI; Biological and behavioral modifiers; Drinking water; Gender; Human; Inorganic arsenic; Methylated arsenicals; Smoking; Toenails; Urine