Styrene metabolism in rats, mice, and humans
Species and strain differences have been reported in investigations of the toxicity of styrene in rats and mice, with mice showing much greater sensitivity. Understanding metabolism is an essential component in elucidating mechanisms associated with chemical-induced toxicity and differences among species or strains. Styrene toxicity is thought to be mediated primarily by oxidation to styrene 7,8-oxide, which undergoes further metabolism via a number of pathways. Scientists at the CIIT Centers for Health Research and their colleagues investigated the metabolism of styrene in rats and mice and compared those findings with parameters measured for human volunteers exposed to styrene. Quantitative differences in the uptake and metabolism of styrene were observed, with mice having greater relative uptake of styrene than rats and humans. Metabolism of styrene 7,8-oxide by glutathione conjugation was considerably higher in mice and rats than in humans. Metabolism to
phenylaceturic acid, possibly involving phenylacetaldehyde as an intermediate, was considerably higher in mice. These comparisons provide critical information for assessing the risk to human health from exposure to styrene.