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Reproductive and Developmental Toxicity of Arsenic in Rodents: A ReviewDepartment of Biomedical Sciences and Pathobiology, Virginia Maryland Regional College of Veterinary Medicine, Virginia Polytechnic Institute and State University, Blacksburg, Virginia, USA
Environmental Carcinogenesis Division, National Health and Environmental Effects Research Laboratory, ORD, US EPA, Research Triangle Park, North Carolina, USA, US Environmental Protection Agency
Department of Biomedical Sciences and Pathobiology, Virginia Maryland Regional College of Veterinary Medicine, Virginia Polytechnic Institute and State University, Blacksburg, Virginia, USA Correspondence: Address correspondence to Amy Wang, Phase II, Duckpond Drive, Blacksburg, VA 24061-0442, USA. E-mail:amywang{at}vt.edu Arsenic is a recognized reproductive toxicant in humans and induces malformations, especially neural tube defects, in laboratory animals. Early studies showed that murine malformations occurred only when a high dose of inorganic arsenic was given by intravenous or intraperitoneal injection in early gestation. Oral gavage of inorganic arsenic at maternally toxic doses caused reduced fetal body weight and increased resorptions. Recently, arsenic reproductive and developmental toxicity has been studied in situations more similar to human exposures and using broader endpoints, such as behavioral changes and gene expression. For the general population, exposure to arsenic is mostly oral, particularly via drinking water, repeated and prolonged over time. In mice and rats, methylated or inorganic arsenic via drinking water or by repeated oral gavage induced male and female reproductive and developmental toxicities. Furthermore, at nonmaternally toxic levels, inorganic arsenic given to pregnant dams via drinking water affected fetal brain development and postnatal behaviors. However, arsenic given by repeated oral gavage to pregnant mice and rats was not morphologically teratogenic. In this review of arsenic reproductive and developmental toxicity in rats and mice, the authors summarize recent in vivo studies and discuss possible underlying mechanisms. The influences of folate, selenium, zinc, and arsenic methylation on arsenic reproductive and developmental toxicity are also discussed.
Key Words: Arsenic Fetus • Folate • In Vivo • Methylation
International Journal of Toxicology, Vol. 25, No. 5,
319-331 (2006) This article has been cited by other articles:
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