IARC MONOGRAPHS ON THE EVALUATION OF CARCINOGENIC ...

STYRENE 503
groups. Only minor general toxic effects (slightly reduced body weight in females) were
observed. [The Working Group noted that the negative results obtained in this study do
not provide adequate assurance of an absence of potential to impair fertility after
exposure to styrene at higher dose levels and by other routes.]
No effects on sperm head morphology or sperm development were found in male
mice exposed to 300 ppm [1280 mg/m 3 ] styrene (6 h per day, five days per week, for five
weeks) (Salomaa et al., 1985). General studies of the chronic and subchronic toxicity of
styrene in several species have not shown testicular pathology at inhalation concentrations
of up to 160 ppm [682 mg/m 3 ] in mice and 1000 ppm [4260 mg/m 3 ] or higher in
other species (rat, rabbit, guinea-pig, rhesus monkey) (Brown et al., 2000). One study in
rats found evidence of testicular toxicity (decreased sperm count and some changes in
testicular pathology) at oral styrene doses of 400 mg/kg bw per day for 60 days
(Srivastava et al., 1989). Srivastava et al. (1992) showed similar decreases in sperm
count and testicular enzymes in postnatally maturing rats after treatment with styrene
(200 mg/kg bw but not 100 mg/kg bw per day) by gavage for the first 60 days of life.
In peripubertal male C57BL/6 mice, free testosterone concentrations in plasma were
strongly reduced after four weeks of exposure to styrene in the drinking-water (50 mg/L;
this resulted in a daily intake of styrene of approximately 12 mg/kg bw). There were no
effects on body weight, testis weight or plasma corticosterone and luteinizing hormone
levels (Takao et al., 2000).
There are only limited data on potential effects of styrene on estrous cyclicity. One
study reported increased estrus cycle length and decreased body weight in rats exposed
to 11.6 ppm [49 mg/m 3 ] styrene (Iziumova, 1972). However, the reporting of this study
is confusing, the duration of estrus was poorly defined, and it is not clear if a comparable
(sham) control group was used. In addition, it seems unlikely based on other studies of
styrene that such a low exposure level would cause effects on body weight (see
comments in Brown et al., 2000).
The potential developmental toxicity of styrene and styrene 7,8-oxide was investigated
in two in-vitro culture systems: micromass cell cultures of rat embryo midbrain or
limb-bud cells and whole-embryo culture. Effects of styrene 7,8-oxide on markers of
differentiation of limb-bud cells were evident at concentrations that had minimal effect
on cell viability. Styrene alone or in the presence of an exogenous mono-oxygenase
system had minimal effects even when tested at much higher concentrations than styrene
7,8-oxide. In whole-embryo culture, styrene 7,8-oxide caused growth retardation and
malformations at somewhat lower levels than those producing embryo mortality
(Gregotti et al., 1994). In another study using postimplantation rat embryos in vitro,
styrene 7,8-oxide was embryotoxic at concentrations more than 20 times lower than
styrene (Brown-Woodman et al., 1994).