IARC MONOGRAPHS ON THE EVALUATION OF CARCINOGENIC ...

STYRENE 521
and immune systems, liver and kidney in exposed workers did not reveal consistent
changes.
Central nervous system effects of styrene were reported in rats, guinea-pigs and
rabbits. Styrene exposure causes liver and lung toxicity in mice and nasal toxicity in rats
and mice.
In humans, there is no evidence for an association between workplace exposure to
styrene and spontaneous abortions, malformations or decreased male fecundity.
In rats, there is some evidence for reduced sperm count and peripubertal animals may
be more sensitive than adult animals. Styrene crosses the placenta in rats and mice. It
increases prenatal death at dose levels causing decreased maternal weight gain.
Decreased pup weight, postnatal developmental delays as well as neurobehavioural and
neurochemical abnormalities have been reported in rats exposed to styrene during preor
postnatal development. In-vitro studies indicate that the potential for developmental
toxicity is much higher for styrene 7,8-oxide than for styrene.
Occupational exposure to styrene leads to formation of O 6 -deoxyguanosine (O 6 -(2hydroxy-1-phenylethyl)-2′-deoxyguanosine-3′-monophosphate)
and N7-deoxyguanosine
adducts in DNA. Low levels of these two adducts were also detected in liver of mice
and rats exposed to styrene.
Inconsistent results have been reported for chromosomal aberrations, micronuclei
and sister chromatid exchange in approximately 30 studies of workers exposed to styrene
in various industries. These studies were predominantly from the reinforced-plastics
industry where styrene exposure is high, but there was no indication of a dose–response
relationship in any of the studies reporting positive results. Induction of chromosomal
aberrations was reported in 12 of 25 studies, sister chromatid exchange in six of 16
studies and micronuclei in three of 14 studies.
Sister chromatid exchange and to a lesser degree chromosomal aberrations were
induced in rodents in vivo and consistently in human lymphocytes in vitro.
Styrene was predominantly inactive in assays for gene mutations in bacteria,
although some studies reported mutations in the presence of a metabolic activation
system.
Data from both laboratory (in vitro and in vivo) and human studies indicate that
styrene exposure can result in low levels of DNA adducts and DNA damage in individuals
who possess the capacity to activate styrene metabolically to styrene 7,8-oxide.
However, as noted above, mice, but not rats, develop lung tumours following styrene
exposure, even though both species form DNA adducts. DNA adducts are also found in
organs other than the lung. Circulating styrene 7,8-oxide may also play a role. However,
the concentration 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 causes cytotoxicity and increased cell proliferation, but the roles 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