Arsenic risk assessment.

We review recent publications by Hopenhayn-Rich et al. and Smith et al. regarding two critical issues in arsenic risk assessment: the role of methylation in the dose-response relationship and the role of internal cancers. Hopenhayn-Rich et al. applied simple linear regression to data from several studies to determine whether the percentage of inorganic arsenic in urine increases with increasing dose. Although their results failed to show a correlation between percent inorganic arsenic and urinary arsenic concentration, their evaluation does not demonstrate the absence of a methylation threshold because of the relatively low level of arsenic in urine and the use of grab samples in evaluating methylating capacity. Using data from an epidemiological study in Taiwan, Smith et al. have indicated that arsenic could be an important risk factor not only for skin cancer (the basis of the current EPA cancer slope factor), but also for several internal cancers including lung, liver, bladder, and kidney. We note the following deficiencies in the analysis of Smith et al: 1) the likely underestimated exposure estimate due to lack of consideration on nonwater sources of arsenic and the underestimate of water consumption, 2) lack of consideration of detoxification in estimating potential risks from low-level exposures typical of the U.S. population, and 3) lack of consideration of key differences, particularly nutritional differences, between the Taiwanese and U.S. populations that could affect potential risks.