Biomarkers of exposure: a case study with inorganic arsenic

The environmental contaminant inorganic arsenic (iAs) is a human toxicant and carcinogen. Most mammals metabolize iAs by reducing it to trivalency, followed by oxidative methylation to pentavalency. iAs and its methylated metabolites are primarily excreted in urine within 4-5 days by most species and have a relatively low rate of bioaccumulation. Intra- and interindividual differences in the methylation of iAs may affect the adverse health effects of arsenic. Both inorganic and organic trivalent arsenicals are more potent toxicants than pentavalent forms. Several mechanisms of action have been proposed for arsenic-induced toxicity, but a scientific consensus has not been achieved. Biomarkers of exposure may be used to quantify exposure to iAs. The most common biomarker of exposure for iAs is the measurement of total urinary arsenic. However, consumption of seafood containing high concentrations of organic arsenic can confound estimation of iAs exposure. Because these organic species are thought to be relatively nontoxic, their presence in urine may not represent increased risk. Speciation of urinary arsenic into inorganic and organic forms, and even oxidation state, gives a more definitive indication of the exposure to iAs. Questions still remain, however, as to how reliably the measurement of urinary arsenic, either total or speciated, may predict arsenic concentrations at target tissues as well as how this measurement could be used to assess chronic exposures to iAs.