home edit2 whole TSD November 2002 PDF format - OEHHA

due to the small numbers of workers involved in the human studies and because of the possibility that
other workplace carcinogens may have been confounders. However, CDHS also noted that though not
conclusive, these studies provide substantial suggestive evidence of ethylene oxide's carcinogenicity in
humans.
The animal studies listed above demonstrate the ability of ethylene oxide to induce tumors in multiple
species (rats and mice) at multiple sites (brain gliomas, mononuclear cell leukemias, peritoneal
mesotheliomas in rats; alveolar/bronchiolar adenomas/carcinomas, malignant lymphomas, mammary
gland adenosarcomas or adenosquamous carcinomas and uterine adenomas/adenosarcomas in mice.
CDHS developed a cancer unit risk for ethylene oxide based on data from the most sensitive sex, site
and species, the female rat mononuclear cell leukemia data from Snellings et al. (1984).
Methodology
The data used to calculate cancer risk from the female rat mononuclear cell leukemia observed in the
Bushy Run Research Center study (Snellings et al., 1984a) are given in Table 7 (US EPA, 1985). The
table differs from Table 2 presented above. The denominators in Table 7.1 include only those animals
whose tissues were examined, that were alive at the time the first leukemia was detected and were thus
at risk for the tumor. There is an extra tumor in the 100 ppm group numerator because it was found in
one of the rats removed for quality control at 18 months and was therefore excluded from Table 2.
CDHS confirmed the EPA numbers by analysis of Table A-73 in the Appendices of the Bushy Run
study (Snellings et al., 1981). Denominators obtained by approaches other than that used by the EPA
do not differ significantly from their approach.
Table 7:
Incidence of mononuclear cell leukemia in female rats among survivors to first tumor
(Adapted from US EPA, 1985 (Table 9-33, p. 9-150)).
Ethylene oxide
exposure
(ppm)
Number with leukemia/corrected
number exposed
Equivalent human
lifetime dose
(mg/kg/day)
0 22/186 (1-1.8%) 0
10 14/71 (19.7%) 0.28
33 24/72 (33.3%) 0.75
100 28/73 (38.4%) 2.11
Using the computer software Global 82 (Crump and Howe, 1982), a linearized multistage procedure
was fit to the female leukemia dose-response data. Doses were first converted to human equivalents
(Tyler and McKelvey, 1980; US EPA, 1985). The female rat leukemia data yielded a maximum
likelihood estimate (MLE) for q 1 , (the linear or slope term, which relates the probability of cancer to the
dose of carcinogen administered in the equation for the multistage procedure) of 0.20 (mg/kg-day) -1 .
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