Characterization of Urinary Arsenic Metabolites for Use as Biomarkers of Susceptibility to Arsenic Toxicity

Abstract

Arsenic is naturally occurring in the environment, and can be found in rocks, soil, water, and air. One main route of human exposure to arsenic is through drinking water from groundwater sources. Chronic exposure to arsenic is associated with cardiovascular, neurological, skin, and cancer- related diseases. However, there is significant variability in susceptibility to arsenic toxicity among humans. Individuals exposed to the same concentration of arsenic can show different clinical symptoms. This variability may partly be because of differences in the metabolism of arsenic to facilitate elimination from the human body. Urine is the main pathway for the elimination of arsenic; and the arsenic compounds (species) in urine can serve as a biomarker of exposure and metabolism. The primary objective of this research was to determine the concentrations of arsenic metabolites in urine samples collected from an arsenic-affected population in Bangladesh. The participants of this study used well water as their drinking water source, which contained arsenic of various concentrations. To enable characterization and determination of arsenic metabolites in human urine, I refined and optimized an analytical method that involved high performance liquid chromatography (HPLC) separation and inductively coupled plasma mass spectrometry (ICPMS) detection. The method was able to quantitatively measure five common arsenic compounds in urine within 10 minutes. These arsenic compounds included inorganic arsenic species, arsenite (As(III)) and arsenate (As(V)), and their methylated metabolites, monomethylarsonic acid (MMA(V)) and dimethylarsinic acid (DMA(V)). The method also enabled the determination of arsenobetaine, an arsenic compound commonly found in seafood. The method had a limit of detection of 0.1 µg/L for AsIII, and 0.05 µg/L for the other four arsenic species. Using the method that I have developed, I determined concentrations of the five arsenic species in the urine of 879 participants from Bangladesh. The summed concentrations of all arsenic species in the urine were in good agreement with the results of total arsenic analysis. The arsenic speciation analysis showed a significant difference in the arsenic metabolite profiles of different exposure groups. The group of participants who had lower than 50 µg/L of total arsenic in their urine showed a higher proportion of DMA and DMA/MMA ratio as compared to those who had higher than 50 µg/L of total arsenic in their urine. These results will contribute to the identification of biomarkers of an individual’s susceptibility to arsenic toxicity.