In our view, adequate long-term carcinogenesis bioassays have not been done on this metal or its common environmental and commercial inorganic derivatives. Enzymatic methylation is thought to detoxify arsenic. One reason given for the apparent lack of carcinogenicity of arsenic in animals is the methylation differential between humans and rodents. This implied lower capacity to detoxify arsenic via methylation may be related to nutrition, particularly with nutrients associated with production of methyl donor groups.
Nutrition appears to play an influential role in sensitivity to arsenic carcinogenesis.
Poor nutrition may be the underlying reason why carcinogenic activity of arsenic is often seen in lower socioeconomic individuals. In arsenic carcinogenesis studies, we recommend the use of a diet with marginally low methyl content rather than the high protein laboratory chows currently used or available on the market. Prior carcinogenicity studies using rodents have consistently ignored this important aspect of arsenic metabolism. Also in our view, we would suggest long-term inhalation studies using arsenic trioxide, the most common arsenic compound considered carcinogenic to humans. Additionally, some experimental efforts could be directed to initiator-promoter systems.