home edit2 whole TSD November 2002 PDF format - OEHHA

incidence of primary brain tumors.
The frequency of multiple primary (benign plus malignant) neoplasms was significantly greater than the
controls in the 100 ppm-exposed male rats. For females all three exposed groups had significantly more
multiple primary neoplasms than controls (p < 0.05).
Lynch et al. (1984) reported the results of a study in male Fischer 344 rats which confirmed the findings
of Snellings et al. (1984a). Groups of 80 weanling rats were exposed to 0 (filtered air), 50 or 100 ppm
99.7% pure ethylene oxide, 7 hours/day, 5 days/week, for two years. Histopathology was performed
on standard sets of 34 tissues plus all gross lesions for all rats that died or were sacrificed. At
approximately 8, 16, and 20 months into the study, rats were treated for 2 to 3 weeks with tetracycline
for pulmonary infections. Mycoplasma pulmonis was confirmed by serology during the 16th month
outbreak. Exposure to ethylene oxide was stopped only for 14 days during the 16th month.
The median survival time and body weight gain were decreased in animals exposed to both
concentrations of ethylene oxide compared with controls, and survival time in the high-dose group was
significantly decreased (p < 0.01). The authors concluded that mortality was affected by ethylene oxide
treatment as well as by the M. pulmonis infection. Rats exposed to 50 or 100 ppm had a higher
incidence than controls of inflammatory lesions of the lungs, nasal cavities, trachea and internal ear as
well as an increased incidence of bronchiectasis and bronchial epithelial hyperplasia. These findings are
consistent with the manifestations seen in chronic respiratory disease complex in rodents.
The incidence of MNCL in animals dying during the study plus the terminal sacrifices was significantly
greater (p = 0.03) in the 50 ppm group, but not the 100 ppm group, than in the controls (Table 5).
Survival in the 100 ppm group was 19% compared to 49% in controls. If the incidence of MNCL of
only the terminally sacrificed rats is compared, a statistically significant increased incidence of MNCL (p
< 0.01) is observed for the 100 ppm group.
Peritoneal mesotheliomas were significantly increased in the 100 ppm group (p = 0.002), but not the 50
ppm group, compared with controls, even in the presence of excess mortality. Use of the Armitage test
for trend suggested a proportional increase in the incidence of mesotheliomas with increased exposure.
The incidence of brain gliomas was increased in the 100 ppm dose group (p < 0.05) compared with
controls (Table 5). Trend analysis suggested a significant increase in gliomas with increased exposure to
ethylene oxide. Two additional rats exposed to 50 ppm and four additional rats exposed to 100 ppm
had increased numbers of glial cells, termed "gliosis." The authors suggested that these cases of gliosis
represent incipient gliomas.
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