Chemico-Biological Interactions 137 (2001) 185–202
The toxicity of styrene to the nasal epithelium
of mice and rats: studies on the mode of action
and relevance to humans
*, Robert Lee
, Alison Toghill
, Valerie Lund
, John Foster
Syngenta Central Toxicology Laboratory, Alderley Park, Macclesﬁeld, Cheshire SK
Institute of Laryngology and Otology, Uni6ersity College London,
s Inn Road, London, UK
Received 7 February 2001; received in revised form 19 April 2001; accepted 23 April 2001
Inhaled styrene is known to be toxic to the nasal olfactory epithelium of both 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 olfactory mucosa and loss of normal cellular organisation. Pretreat-
ment of mice with 5-phenyl-1-pentyne, an inhibitor of both CYP2F2 and CYP2E1 com-
pletely prevented the development of a nasal lesion on exposure to styrene establishing 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 vitro, have provided an explanation for the increased sensitivity of the mouse
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. Metabolism 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 efﬁciently, indicating that
styrene is unlikely to be toxic to the human nasal epithelium. © 2001 Elsevier Science Ireland
Ltd. All rights reserved.
Styrene; Nasal toxicity; Rodent; Human
* Corresponding author. Tel.: +44-1625-515458; fax: +44-1625-586396.
firstname.lastname@example.org (T. Green).
0009-2797/01/$ - see front matter © 2001 Elsevier Science Ireland Ltd. All rights reserved.