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and the males at 25 months. Postmortem examinations were performed on all rats. Histopathologic
examinations of about 50 tissues were performed on rats from the 100 ppm and two control groups that
were killed at the 6 month and final intervals and on rats in any group that died or were killed in a
moribund state. About 15 major organs and tissues from rats in the 100 ppm and both control groups
were examined microscopically at 12 and 18 months. At 6, 12, and 18 months, only tissues with gross
lesions were examined from the 10 and 33 ppm groups. At the end of the study about 20 major organs
and tissues from the rats in the 10 and 33 ppm groups were examined. During the 15th month of
exposure, rats in all groups became infected with sialodacryoadenitis virus. This resulted in a loss in
body weight in all groups and increased mortality in the females exposed to 100 ppm compared with the
other groups. Exposure to ethylene oxide was stopped for 2 weeks after which time body weights,
clinical signs, and mortality rates returned to preinfection status. The authors concluded that this
outbreak was unlikely to have affected the results of the study. Cumulative percentage mortality did not
increase significantly in the 10 or 33 ppm dose groups, but did increase in the 100 ppm dose groups,
after 22 months exposure for males and after 21 months for females.
Table 2:
Tumor incidence in F344 rats exposed to ethylene oxide by inhalation for 24 months
(adapted from Snellings et al., 1984).
ppm ethylene oxide
C1 C2 10 33 100
Sex
# animals examined grossly
male 48 49 51 39 30
female 60 56 54 48 26
Sex Tumor type # animals with tumors
male spleen mononuclear cell leukemia 5 8 9 12 9
female 5 6 11 14 15 *
male peritoneal mesothelioma 1 1 2 4 4
male pituitary adenoma 16 13 15 13 12
C1, C2 control groups
* significantly greater than appropriate control incidence (p < 0.001)
Tumor incidence was not significantly increased at 18 months of exposure; however, increased
incidences of several types of tumors were observed in groups sacrificed at 24 and 25 months, the end
of the study for female and male rats, respectively (Table 2).
The incidence of mononuclear cell leukemia (MNCL) was increased for both sexes in all dose groups,
but was statistically significant only for females treated with 100 ppm ethylene oxide. A positive
dose-related increase in MNCL incidence in females was observed (p < 0.01). A statistically significant
trend was not observed for males. When the incidence of MNCL in rats killed at the end of the study is
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