title: Arsenic exposure and toxicology: a historical perspective.
abstract: 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, has been used as a pesticide, a chemotherapeutic agent and a constituent of consumer products. In some areas 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 metals and covalent bonds with hydrogen, oxygen, carbon, and other elements. Environmentally relevant forms of arsenic are inorganic and organic existing in the trivalent or pentavalent state. 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 pentavalency. Trivalent arsenic is generally more toxicologically potent than pentavalent arsenic. 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 mode of action of arsenic for 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 and the recent development of animal models for arsenic carcinogenicity, understanding of the toxicology of arsenic will continue to improve.
authors.affiliation: Office of Research and Development, National Health and Environmental Effects Research Laboratory, U.S. Environmental Protection Agency, Research Triangle Park, North Carolina 27711, USA. hughes.michaelf@epa.gov
authors.forename: Michael F
authors.initials: MF
authors.lastname: Hughes
authors.forename: Barbara D
authors.initials: BD
authors.lastname: Beck
authors.forename: Yu
authors.initials: Y
authors.lastname: Chen
authors.forename: Ari S
authors.initials: AS
authors.lastname: Lewis
authors.forename: David J
authors.initials: DJ
authors.lastname: Thomas
mesh_terms: D000818:Animals; D020261:Arsenic Poisoning / Q000266:history*; D001152:Arsenicals / Q000009:adverse effects / Q000266:history*; D002274:Carcinogens, Environmental / Q000266:history* / Q000633:toxicity; D004781:Environmental Exposure / Q000009:adverse effects / Q000266:history*; D049673:History, 20th Century; D049674:History, 21st Century; D006801:Humans; D014116:Toxicology / Q000266:history*
chemical_list: D001152:Arsenicals; D002274:Carcinogens, Environmental