State of the science review of the health effects of inorganic arsenic: Perspectives for future research.

Human exposure to inorganic arsenic (iAs) is a global health issue. Although there is strong evidence for iAs-induced toxicity at higher levels of exposure, many epidemiological studies evaluating its effects at low exposure levels have reported mixed results. We comprehensively reviewed the literature and evaluated the scientific knowledge on human exposure to arsenic, mechanisms of action, systemic and carcinogenic effects, risk characterization, and regulatory guidelines. We identified areas where additional research is needed. These priority areas include: (1) further development of animal models of iAs carcinogenicity to identify molecular events involved in iAs carcinogenicity; (2) characterization of underlying mechanisms of iAs toxicity; (3) assessment of gender-specific susceptibilities and other factors that modulate arsenic metabolism; (4) sufficiently powered epidemiological studies to ascertain relationship between iAs exposure and reproductive/developmental effects; (5) evaluation of genetic/epigenetic determinants of iAs effects in children; and (6) epidemiological studies of people chronically exposed to low iAs concentrations.