IARC MONOGRAPHS ON THE EVALUATION OF CARCINOGENIC ...

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Circulating styrene 7,8-oxide may also play a role. However, the concentration of
this metabolite in rat blood is two orders of magnitude higher than in the mouse. The lung
tumours in mice probably develop as a result of in-situ formation of styrene 7,8-oxide
which leads to cytotoxicity and increased cell proliferation, but a role of circulating
styrene 7,8-oxide and of DNA adducts cannot be discounted.
Based on metabolic considerations, it is likely that the proposed mechanism
involving metabolism of styrene to styrene 7,8-oxide in mouse Clara cells is not operative
in human lungs to a biologically significant extent. However, based on the observations
in human workers regarding blood styrene 7,8-oxide, DNA adducts and chromosomal
damage, it cannot be excluded that this and other mechanisms are important for
other organs.
5.1 Exposure data
5. Summary of Data Reported and Evaluation
Styrene is a commercially important monomer which is used extensively in the
manufacture of polystyrene resins (plastic packaging, disposable cups and containers,
insulation) and in copolymers with acrylonitrile and/or 1,3-butadiene (synthetic rubber
and latex, reinforced plastics). Human exposure occurs at levels of milligrams per day
during its production and industrial use and at much higher levels in the glass fibrereinforced
plastics industry. Exposure to the general population occurs at levels of micrograms
per day due mainly to inhalation of ambient air and cigarette smoke and intake of
food that has been in contact with styrene-containing polymers.
5.2 Human carcinogenicity data
IARC MONOGRAPHS VOLUME 82
Retrospective cohort studies of styrene have been conducted in three types of
industry: production of styrene monomer and styrene polymers, production of glass
fibre-reinforced plastic products, and production of styrene–butadiene rubber.
In a European multinational cohort study of workers in the glass fibre-reinforced
plastics industry (the largest component of which was Danish), there was no excess
mortality from lymphatic and haematopoietic neoplasms in the entire cohort in comparison
with the general population, but the results may have been biased by problems with
mortality ascertainment in some of the sub-cohorts. In internal analyses, using unexposed
cohort members as the comparison group, the risk of lymphatic and haematopoietic neoplasms
was significantly increased among exposed workers after more than 20 years
since their first exposure to styrene, and increased with increasing intensity of exposure
but not with increasing cumulative exposure to styrene.
Another study of cancer incidence in the reinforced-plastics industry conducted in
Denmark involved many workers who had been included in the European study. Overall,