The toxicity of styrene to the nasal epithelium of mice and rats: studies on the mode of action and relevance to humans

Inhaled styrene is known to be toxic to the nasal olfactory epithelium of b oth mice and rats, although mice are markedly more sensitive. In this study , the nasal tissues of mice exposed to 40 and 160 ppm styrene 6 h/day for 3 days had a number of degenerative changes including atrophy of the olfacto ry mucosa and loss of normal cellular organisation. Pretreatment of mice wi th 5-phenyl-1-pentyne, an inhibitor of both CYP2F2 and CYP2E1 completely pr evented the development of a nasal lesion on exposure to styrene establishi ng that a metabolite of styrene, probably styrene oxide, is responsible for the observed nasal toxicity. Comparisons of the cytochrome P-450 mediated metabolism of styrene to its oxide, and subsequent metabolism of the oxide by epoxide hydrolases and glutathione S-transferases in nasal tissues in vi tro, have provided an explanation for the increased sensitivity of the mous e to styrene. Whereas cytochrome P-450 metabolism of styrene is similar in rats and mice, the rat is able to metabolise styrene oxide at higher rates than the mouse thus rapidly detoxifying this electrophilic metabolite. Meta bolism of styrene to its oxide could not be detected in human nasal tissues in vitro, but the same tissues did have epoxide hydrolase and glutathione S-transferase activities, and were able to metabolise styrene oxide efficie ntly, indicating that styrene is unlikely to be toxic to the human nasal ep ithelium. (C) 2001 Elsevier Science Ireland Ltd. All rights reserved.