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Arsenic Exposure and Toxicology: A Historical Perspective
Citation:
HUGHES, M. F., B. Beck, Y. Chen, A. S. Lewis, AND D. J. THOMAS. Arsenic Exposure and Toxicology: A Historical Perspective. TOXICOLOGICAL SCIENCES. Society of Toxicology, RESTON, VA, 123(2):305-32, (2011).
Impact/Purpose:
This is a review manuscript of the exposure, metabolism, mode of action and epidmeiology of arsenic. The manuscript examines these areas in a historical aspect.
Description:
The metalloid arsenic is a natural environmental contaminant to which humans are routinely exposed in food, water, air and soil. Arsenic has a long history of use as a homicidal agent, but in the past 100 years arsenic, in various forms, has also been used as a pesticide and a chemotherapeutic agent. It has also been used as a constituent of several different consumer products, including pigments and paints, glass and semiconductors. Anthropogenic sources of arsenic in air include burning of metal ores and coal and in soil its use as a pesticide. In some area of the world, high levels of arsenic are naturally present in drinking water and are a toxicological concern. There are several structural forms and oxidation states of arsenic because it forms alloys with other metals and covalent bonds with hydrogen, oxygen, carbon, sulfur and other elements. Environmentally relevant forms of arsenic are inorganic and organic and exist in the trivalent or pentavalent state. The chemistry of arsenic has a direct effect on its metabolism and toxicity. Metabolism of arsenic, catalyzed by arsenic (+3 oxidation state) methyltransferase, is a sequential process of reduction from pentavalency to trivalency followed by oxidative methylation back to pentatavalency. Trivalent arsenic is generally more toxicologically potent than pentavalent arsenic. The metabolism of arsenic was commonly considered a detoxication reaction because of the facilitated excretion of pentavalent methylated arsenic. However, with the detection of trivalent methylated arsenicals in excreta because of enhanced analytical capabilities and recognition of their inherent toxicity, the methylation of arsenic may now be considered an activation process for some arsenic-related diseases. Acute effects of arsenic range from gastrointestinal distress to death. Depending on the dose, chronic arsenic exposure may affect several major organ systems. A major concern of ingested arsenic is cancer, primarily of skin, bladder and lung. The precise mode of action of arsenic for most of its disease endpoints is currently under study. Two key areas are the interaction of trivalent arsenicals with sulfur in proteins and the ability of arsenic to generate oxidative stress. With advances in technology (e.g., 'omics') and the recent development of animal models for arsenic carcinogenicity, understanding of the toxicology of arsenic will continue to improve.
