IARC MONOGRAPHS ON THE EVALUATION OF CARCINOGENIC ...

478
incidence of lung tumours was seen in males or females at 12 or 18 months. The increase
seen after 24 months was largely in small tumours, as demonstrated by a decreased
average tumour size compared with controls. The fact that increased tumour incidences
was seen only later than 18 months and the small size of these tumours indicated that
these were late-developing tumours. No difference in tumour morphology between
control and treated mice was seen. Epithelial hyperplasia of the terminal bronchioles
extending into the alveolar duct was seen in a dose-related pattern at all interim and
terminal necropsies. Hyperplasia was preceded by decreased eosinophilic staining of
Clara cells and cellular crowding (Cruzan et al., 2001).
3.3.2 Rat
IARC MONOGRAPHS VOLUME 82
Groups of 30 male and 30 female Sprague-Dawley rats, 12 weeks of age, were
exposed by inhalation to 0, 25, 50, 100, 200 or 300 ppm [106, 213, 430, 850 or
1280 mg/m 3 ] styrene (99.8% pure) for 4 h per day, five days per week, for 12 months
(and then held until death). In females, malignant mammary tumours were diagnosed in
6/60 (10%), 6/30 (20%), 4/30 (13%), 9/30 (30%), 12/30 (40%) and 9/30 (30%) rats
inhaling 0, 25, 50, 100, 200 or 300 ppm, respectively. For total mammary tumours, the
incidences were 34/60 (57%), 24/30 (80%), 21/30 (70%), 23/30 (77%), 24/30 (80%) and
25/30 (83%) for the respective exposure levels (Conti et al., 1988). [The Working Group
noted the short duration of treatment, the incomplete reporting of the study and the high
incidence of spontaneous mammary tumours in animals of this strain.]
Groups of 60 male and 60 female Charles River CD rats, approximately four weeks
of age, were exposed by whole-body inhalation to 0, 50, 200, 500 or 1000 ppm [213, 850,
2130 or 4260 mg/m 3 ] styrene (> 99.5% pure) for 6 h per day on five days per week for
104 weeks. Females exposed to 500 and 1000 ppm weighed less than controls throughout
the study. However, there was a dose-related increase in survival; at termination, survival
was 48, 47, 48, 67 and 82% in females exposed to 0, 50, 200, 500 and 1000 ppm,
respectively. There were no increased incidences of tumours related to styrene exposure.
A dose-dependent decrease in mammary tumours in females was reported. Mammary
adenocarcinomas were diagnosed in 20/61 (33%), 13/60 (22%), 9/60 (15%), 5/60 (8%)
and 2/60 (3%) female rats exposed to 0, 50, 200, 500 or 1000 ppm styrene, respectively,
for two years. A decrease in benign mammary fibroadenomas (including those with epithelial
atypia) was seen, the incidence being 27/61 (44%), 22/60 (37%), 18/60 (30%),
21/60 (35%) and 19/60 (32%) for the above exposure levels, respectively (Cruzan et al.,
1998).