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EC number: 202-476-7
CAS number: 96-09-3
In a sub-chronic study, groups of 10 male and 10 female F344 rats
were given doses of styrene oxide (in corn oil) corresponding to 3000,
1500, 750, 360 and 180 mg/kg bw three times a week. A control group was
given only corn oil. These groups were treated for 24 weeks. In addition
12 rats of each sex were given 1500 or 360 mg/kg bw for interim
sacrifice of 4 rats at 5, 10, and 15 weeks of the study; 12 additional
controls given vehicle were also used for interim sacrifice.
Decrease survival was seen in the rats given the highest dose of
styrene oxide. Of the rats given 3000 mg/kg bw 30 % of the males dies in
the first 5 weeks and 40 % of the females died in the first 5 weeks; all
were dead at 10 weeks. Of the rats given 1500 mg/kg bw 20 % of the
females and 30 % of the males died at 24 weeks. Histopathologic
examination of the animals revealed basal cell hyperplasia and
hyperkeratosis of the forestomach and lesions in the liver, including
hemorrhagic necrosis in those that died; several rats also had renal
tubular epithelial degeneration or necrosis. Among the rats given lower
doses, all of which survived, the changes observed histologically were
some degree of liver cell hyperplasia, which varied from mild to
moderate, and renal tubular degeneration in a few cases. There was no
significant depression of weight gain among the animals receiving the
three lowest doses of styrene oxide, but there was some decrease (> 10
%) at the two highest doses. The diffuse liver cell hyperplasia was
somewhat greater in the group of rats given 750 mg/kg bw styrene oxide
than in the group given 360 mg/kg bw styrene oxide in which it was only
mild at most.
A MTD of 500 mg/kg bw was established by the study author for the
development of a chronic carcinogenicity study.
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