Environment and Breast Cancer: Science Review


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ethylene oxide
CAS RN 75-21-8



Cancer studies: Experimental details
 
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Dunkelberg H. Carcinogenicity of ethylene oxide and 1,2-propylene oxide upon intragastric administration to rats. Br J Cancer 1982;46(6):924-33.
Notes
Mammary tumors increase at low dose but return to control levels at high dose. Control 4/50, 1st dose 13/50, 2nd dose 1/50 (females only in this study) NTP TR326 evaluated this study and only highlighted the stomach tumors, saying "the incidence of tumors in other organs were similar to dosed and control rats" Uncommon for them to have used a positive contol.
Route
Route of chemical administration: dermal, inhalation, gavage (delivery directly into the stomach), in feed, subcutaneous injection (under the skin), or intraperitoneal injection (into the cavity that contains the abdominal organs).
gavage
Species
Mostly rat or mouse, though some studies use hamster or monkeys.
Rat
Sexes
F for female, M for male.
female
Strain
Strain information for the animal species used in the study.
Sprague-Dawley
Doses
Dosage, frequency, and duration of treatment; the sizes of the groups of animals involved and what age the animals were at the beginning of the study.
7.5 and 30 mg/kg body wt in salad oil twice weekly to groups of 50 rats for 107 weeks (with an additional 4 nontreated weeks near the end while some rats recovered from pneumonia). When pneumonia struck, rats were given chloramphenicol subcutaneously and tylosin-tartrate was added to the drinking water for 3 weeks. There were three additional groups: a vehicle control group, an untreated group, and a positive control group that received beta-propiolactone for 100 wks. Rats were 100 days old (14 wks) at start of experiment.
Time after cessation of dosing
How long the animals were observed after the chemical was no longer being administered and before death of the animals.
Possibly 39 weeks. Article is unclear on whether start of dosing corresponds with start of experiment.
Mammary tumors, benign
Development of benign mammary tumors, reported as a series of fractions. The numerators represent the number of animals that developed benign mammary tumors and the denominators represent the total number of animals receiving the particular dose of chemical. Where available, the denominator will reflect the number of animals alive when the first tumor developed. Otherwise, it will reflect the number of animals examined. The order of the fractions reflects the level of chemical treatment, from no dose (controls) on the left to the highest dose on the right. Where available, the histological type of the tumors will be indicated, i.e. adenoma or fibroadenoma.

Additional information, in development, includes statistical significance and trend information. We plan to indicate whether a particular treatment group’s ratio of mammary tumors related to the control is statistically significantly elevated, as determined by the author. This is indicated with an asterisk (*). We will also include information indicating whether there was an increasing, statistically significant dose response trend reported by CPDB. Results that are statistically significant at p < 0.05 are labeled "T+" and statistical significance between 0.05 and 1.0 is labeled "T~". Where there is no dose-related effect or the trend is identified as decreasing with dose, results are labeled here as "Tna."
Control 4/50, 1st dose 13/50, 2nd dose 1/50 Fibroadenomas
Comments
This field contains information on the survival rates of the animals and the body weight trends in order to evaluate whether these factors were likely to have affected the generation of mammary gland tumors. Mammary gland tumors tend to develop later in an animal’s life, so studies with lowered survival could mean that animals died before mammary gland tumors could develop. Decreased weight (perhaps due to toxicity of the chemical) can decrease the development of tumors. This field may also contain other comments about the design or outcome of the study.
Low dose animals had similar survival to controls. High dose died earlier from tumors.
Other tumors
A list of other tumors that developed in the study that were treatment related.
stomach, forestomach
CPDB TD50 (mg/kg-d)
Data excerpted from the CPDB database that is defined as the "dose-rate in mg/kg body wt/day which, if administered chronically for the standard lifespan of the species, will halve the probability of remaining tumorless throughout that period". The CPDB calculated values for all tumor endpoints listed as well as for total tumors. The range of mammary gland tumors TD50s is provided, as well as an overall range.
Mammary 10.0, overall 7.43-10.6