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ethylene oxide significantly decreased the time to tumor in males (p < 0.01) and females (p < 0.0001).
From the time of the 18-month sacrifice until the end of the study, the incidence of brain tumors,
including gliomas (twelve astrocytomas, one oligodendroglioma, two mixed gliomas), granular cell
tumors, and malignant reticulosis was increased in both sexes. The classification of brain tumors was
based on light microscopic cytomorphologic features and on patterns of growth and infiltration.
Immunohistochemical staining was not done; thus, the cellular origin of these tumors remained
unresolved.
Data on tumors for rats killed at 18 or 24 months and those who died spontaneously or were sacrificed
due to morbidity were further evaluated by Garman et al. (1985, 1986). The first brain tumors were
noted in animals killed at 18 months. The combined incidence of all three tumor types is shown in Table
4. The incidence in the 100 ppm and 33 ppm groups was significantly increased (p = 0.004 and p =
0.027, respectively) compared with the controls. In females a statistically non-significant, dose-related
increase was noted in the combined incidence of these three tumor types (Table 4). The IARC working
group (1985) noted that combining the three different histological types of tumors precluded a proper
evaluation of the effects of ethylene oxide on the brain. (The IARC working group did not have the
1985 paper by Garman et al. available and based their results on Snellings et al. 1984a). However,
even when only the gliomas are considered, a dose-related increase in tumor frequency is also observed
(Table 4).
Table 4:
Statistical analyses on adjusted ratios of primary brain tumor frequencies in F344 rats
exposed to ethylene oxide for two years (Adapted from Garman et al., 1985)
Tumor type Sex ppm ethylene oxide
0 * 10 33 100
Gliomas males 1/181 (0.6%) 0/92 (0%) 3/85 (3.5%) 6/87 (6.9%)
females 0/187 (0%) 1/94 (1.1%) 2/90 (2.2%) 2/78 (2.6%)
Gliomas,malignant reticulosis
and granular cell tumors
males 1/181 (0.6%) 1/92 (1.1%) 5/85 (5.9%) 7/87 (8.0%)
females 1/188 (0.5%) 1/94 (1.1%) 3/92 (3.3%) 4/80 (5.0%)
(a) p = 0.011; (b) p = 0.195; (c) p = 0.172; (d) p = 0.004; (e) p = 0.027; (f) p = 0.058
* control groups C1 and C2
When the data are adjusted for early deaths, the Cox test statistic for adjusted trends in males is
significant (p < 0.001) for gliomas or the combination of the three tumor types. In females, p = 0.023
for gliomas only and p = 0.001 for the three tumor types combined. Comparison of the controls with
historical controls indicates that the concurrent group and the 10 ppm groups had the expected
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