title: Systemic indicators of inorganic arsenic toxicity in four animal species.
abstract: The effect of arsenic compounds depends on the chemical form and is specific for certain organs. The lack of specific biological indicators for the effects of each arsenic species makes it difficult to differentiate their toxicity. Five prospective biological indicators of systemic toxicity were examined at time points ranging from 15 min to 24 h using male Sprague-Dawley rats, B6C3F1 mice, Golden-Syrian hamsters, and Hartley guinea pigs, following intraperitoneal dosing with 0.1 and 1 mg/kg sodium arsenite. Rats and mice were also dosed with 1 mg/kg sodium arsenate. Total blood arsenic levels were determined in all animal species to show that exposure occurred and as an index of the severity of the change is an indicator of toxicity. Total blood arsenic levels were increased in all animal species. This increase was dose, arsenic species, and animal dependent. Renal pyruvate dehydrogenase activity was significantly decreased at early time points in mice, hamsters, and guinea pigs, and at later time points in rats dosed with arsenite. Rats and mice dosed with arsenate also exhibited PDH decrease at early time points. Blood hematocrit and glucose were increased in the rat and guinea pig, respectively, after arsenite administration. Creatinine and urea nitrogen were found to be unresponsive to arsenic in most animal species. Data suggested that the mouse and secondly the hamster appear to be the most appropriate animal models for the study of acute arsenic toxicity.
authors.affiliation: Department of Pharmacology and Toxicology, Center for Toxicology's Superfund Basic Research Program, College of Pharmacy, University of Arizona, Tucson 85721, USA.
authors.forename: R D
authors.initials: RD
authors.lastname: Mitchell
authors.forename: F
authors.initials: F
authors.lastname: Ayala-Fierro
authors.forename: D E
authors.initials: DE
authors.lastname: Carter
mesh_terms: D000818:Animals; D001149:Arsenates / Q000633:toxicity*; D001151:Arsenic / Q000097:blood; D018053:Arsenites / Q000633:toxicity*; D001786:Blood Glucose; D001806:Blood Urea Nitrogen; D003404:Creatinine / Q000097:blood; D006224:Cricetinae; D004791:Enzyme Inhibitors / Q000633:toxicity*; D006168:Guinea Pigs; D006400:Hematocrit; D007274:Injections, Intraperitoneal; D007668:Kidney / Q000187:drug effects / Q000201:enzymology; D008297:Male; D008647:Mesocricetus; D051379:Mice; D011768:Pyruvate Dehydrogenase Complex / Q000037:antagonists & inhibitors / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley; D017670:Sodium Compounds / Q000633:toxicity*; D013045:Species Specificity
chemical_list: D001149:Arsenates; D018053:Arsenites; D001786:Blood Glucose; D004791:Enzyme Inhibitors; D011768:Pyruvate Dehydrogenase Complex; D017670:Sodium Compounds; C017947:sodium arsenite; C009277:sodium arsenate; D003404:Creatinine; D001151:Arsenic