IARC MONOGRAPHS ON THE EVALUATION OF CARCINOGENIC ...

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The increased risks for lymphatic and haematopoietic neoplasms observed in some
of the studies are generally small, statistically unstable and often based on subgroup
analyses. These findings are not very robust and the possibility that the observations are
the results of chance, bias or confounding by other occupational exposures cannot be
ruled out.
5.3 Animal carcinogenicity data
Styrene was tested for carcinogenicity in mice in one inhalation study and four oral
gavage studies. In the inhalation study, in male mice there was an increase in the
incidence of pulmonary adenomas and in female mice, there was an increase in the
incidence of pulmonary adenomas, and only an increase in that of carcinomas in the
high-dose group. Two of the gavage studies were negative. The other two were considered
inadequate for an evaluation of the carcinogenicity of styrene. A screening study
by intraperitoneal administration also did not find an increase in tumour incidence or
multiplicity in mice.
Styrene was tested for carcinogenicity in rats in four gavage studies, one drinkingwater
study and two inhalation studies. Overall, there was no reliable evidence for an
increase in tumour incidence in rats.
Styrene 7,8-oxide is a major metabolite of styrene and has been evaluated previously
(IARC, 1994b). The evaluation at that time was that there was sufficient evidence in
experimental animals for the carcinogenicity of styrene 7,8-oxide.
5.4 Other relevant data
IARC MONOGRAPHS VOLUME 82
Styrene is absorbed following exposure via inhalation, dermal contact and orally in
humans and laboratory animals. In humans, approximately 70% of the inhaled dose is
absorbed. Styrene is distributed throughout the body, with the highest concentration
generally found in adipose tissue. There are both quantitative and qualitative interspecies
differences in styrene metabolism. In humans, styrene is metabolized primarily via the
styrene 7,8-oxide pathway to be excreted in the urine as mandelic and phenylglyoxylic
acids. In rodents, but not in humans, glutathione conjugation of styrene 7,8-oxide to form
mercapturic acids is an important metabolic pathway. Metabolism of styrene to 1- and
2-phenylethanol and then to phenylacetaldehyde and finally to phenylacetic, phenylaceturic
and hippuric acids is more important in animals than in humans.
CYP2E1 and CYP2F are the most important cytochrome P450 enzymes in rodents
and humans responsible for the metabolism of styrene to styrene 7,8-oxide. In addition,
CYP2B6 may be important in humans. In vitro, the rates of metabolism of styrene to
styrene 7,8-oxide are much higher in mouse lung than in rat or human lung.
Occupational styrene exposure causes central and peripheral nervous system effects
in humans. It causes a reversible decrease in colour discrimination and in some studies
effects on hearing have been reported. Studies of effects of styrene on the haematopoietic