Inorganic
arsenic is a ubiquitous environmental contaminant that has long been considered a human
carcinogen. Recent studies raise further concern about the
metalloid as a major, naturally occurring
carcinogen in the environment. However, during this same period it has proven difficult to provide experimental evidence of the carcinogenicity of inorganic
arsenic in laboratory animals and, until recently, there was considered to be a lack of clear evidence for carcinogenicity of any arsenical in animals. More recent work with arsenical methylation metabolites and early life exposures to inorganic
arsenic has now provided evidence of carcinogenicity in rodents. Given that
tens of millions of people worldwide are exposed to potentially unhealthy levels of environmental
arsenic, in vivo rodent models of
arsenic carcinogenesis are a clear necessity for resolving critical issues, such as mechanisms of action, target tissue specificity, and sensitive subpopulations, and in developing strategies to reduce
cancers in exposed human populations. This work reviews the available rodent studies considered relevant to carcinogenic assessment of
arsenicals, taking advantage of the most recent review by the International Agency for Research on
Cancer (IARC) that has not yet appeared as a full monograph but has been summarized (IARC, 2009 , IARC Special Report: Policy, Vol. 10. Lyon: IARC Press, 453–454). Many valid studies show that
arsenic can interact with other
carcinogens/agents to enhance
oncogenesis, and help elucidate mechanisms, and these too are summarized in this review. Finally, this body of rodent work is discussed in light of its impact on mechanisms and in the context of the persistent argument that
arsenic is not carcinogenic in animals.