I. Introduction 250

II. Methods 251

A. Laboratory methods 251

B. Statistical analysis 252

III. Results 253

IV. Discussion 255

Acknowledgements 258

References 258

Abstract Urinary arsenic is used as a biomarker of occupational or high environmental arsenic exposure and the relative concentrations of urinary metabolites (e.g., inorganic arsenic, monomethylarsonic acid (MMA), and dimethylarsinic acid (DMA)) are thought to be, at least in part, under genetic control. However, there are limited data on urinary arsenic in populations exposed to environmental levels typical of the U.S. As part of a study of individuals exposed to arsenic through drinking water in New Hampshire, we examined the association between specific urinary fractions of arsenic and drinking water and toenail concentrations and examined whether the distribution of urinary arsenic species differs by GSTM1 genotype. We recruited 99 individuals between the ages of 25 and 74 years for the study. Water arsenic ranged from undetectable (<0.01 mg/L) to 54.1 mg/L based on high resolution ICP-MS with hydride generation. We tested urine samples using HPLC with hydride generation atomic fluorescence detection and detected arsenic in 77 of the 92 samples (range = less than 1 mg/L to 85.4 mg/L). Only about one fourth of participants had detectable concentrations of inorganic arsenic or MMA, whereas over 80% had detectable DMA. All toenail samples contained at least trace amounts of arsenic using neutron activation analysis (range = 0.01 to 0.53 mg/g). Water and toenail arsenic concentrations correlated with urinary concentrations of MMA and DMA but not inorganic arsenic. Further, water and toenail concentrations were related to the ratio of MMA to DMA but not the ratio of inorganic arsenic to MMA. The percentages or ratios of the urinary fractions did not statistically differ between those with GSTM1 null or wildtype. Our results have important implications for studies of populations in the U.S. and elsewhere with drinking water containing low but potentially harmful levels of arsenic.

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