home edit2 whole TSD November 2002 PDF format - OEHHA

combined with the incidence in the rats dying spontaneously or euthanized when moribund, a statistically
significant increase also occurs in females exposed to 33 ppm (p < 0.01) and 100 ppm (p < 0.001)
(Table 3). A significant increase was not observed in males. A mortality-adjusted trend analysis
revealed a significant positive trend for females (p < 0.005) and males (p < 0.05). The time to first
tumor was not significantly decreased for MNCL in the exposed rats, but trend analysis indicated earlier
tumor development.
Table 3:
Tumor incidences in F344 rats exposed to ethylene oxide which died spontaneously,
were killed when moribund, or were killed after 24 months of exposure (adapted from
Snellings et al., 1981 and cited in US EPA, 1985).
Sex, Tumor type
ppm ethylene oxide
C1 C2 10 33 100
spleen mononuclear cell
leukemia
males 20/80 (25%) 18/80 (23%) 21/80 (26%) 23/80 (29%) 25/80 (31%)
females 9/80 (11%) 13/76 (17%) 14/80 (18%) 24/80 a (30%) 27/80 b (34%)
peritoneal mesothelioma
males 2/80 (3%) 1/80 (1%) 3/80 (4%) 6/80 c (8%) 21/80 d (26%)
C1, C2 control groups
a
p < 0.01 compared to C1 and combined controls, p < 0.05 compared to C2
b
p < 0.001 compared to C1 and combined controls, p < 0.05 compared to C2
c
p < 0.001 compared to C1, C2 and combined controls
d
not significant compared to C1 or C2; p < 0.05 compared to combined controls
Note: These data are from US EPA (1985); US EPA questioned whether microscopic examination of
all tissues or only tissues with gross lesions was performed on animals that died spontaneously or were
killed when moribund. Information from Snelling et al. (1984) indicates that histopathology was
performed on all tissues from these animals.
The increased incidence of peritoneal mesotheliomas observed in males treated with ethylene oxide for
24 months (Table 2) was not statistically significant; however, when the rats that died spontaneously or
were euthanized when moribund are included, a statistically significant increase (p < 0.001) for the
high-dose group compared with controls was observed (Table 3, data from US EPA, 1985). A
mortality-adjusted trend analysis showed a highly significant relationship (p < 0.005) between ethylene
oxide exposure and induction of peritoneal mesotheliomas. Snellings et al. state that this observation
indicates that exposure to ethylene oxide was associated with this earlier occurrence of mesotheliomas.
Although the incidence of pituitary adenomas was not significantly increased in either sex, exposure to
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