Arsenic Metabolism and Toxicity in Humans and Animals: Racial and Species Differences

Susceptibility to the toxic effects of arsenic is influenced by an organism’s capacity for arsenic metabolism. To fully understand this potential, the pathways and properties of arsenic species (trivalent, pentavalent, methylated, or thiolated) as well as glutathione conjugates in the animal or human body must be assessed. Notably, the metabolism of arsenic may comprise detoxification as well as bioactivation processes. Because of the large difference in arsenic methylation capacity and binding affinity toward red blood cell in different animals, an animal model for studies involving human arsenic metabolism and toxicity has not yet been fully established. Individual and ethnic variations in the arsenic methylation capacity of humans are likely explained by genetic polymorphisms of arsenic metabolic enzymes. In particular, the genotype of arsenite methyltransferase (AS3MT) can highly influence the susceptibility to arsenic methylation and thus may be useful to assess the risk of arsenic exposure in humans.