Environment and Breast Cancer: Science Review

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Key References
Abbreviations
 

ethylene oxide
CAS RN 75-21-8

Chemical Summary
Exposure and Risk Assessment
Cancer Studies
 


Cancer studies: Mammary gland tumors
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Originating list
The list(s) or database(s) in which the chemical was identified as showing an increase in mammary gland tumors. CPDB: Carcinogenic Potency Database, IARC: International Agency for Research on Chemicals Monographs on the Evaluation of Carcinogenic Risk of Chemicals to Man summaries, NTP TR: National Toxicology Program (NTP) Technical Reports, NTP 11ROC: NTP 11th Report on Carcinogens, CCRIS: Chemical Carcinogenesis Research Information Service.
Carcinogenicity Potency Database, National Toxicology Program studies, IARC Monographs
Mammary gland tumor summary
A summary of findings related to mammary gland tumors, most often excerpted from IARC Monographs or the NTP 11th ROC, and, in some cases, supplemented by our evaluation of individual studies and reviews, is available for the priority chemicals and 67 others.
Two studies have noted mammary tumors. Both show higher incidence at the lower dose than the higher dose. One of the "negative" studies only used male rats. NTP 11th ROC: Sites of tumor induction in mice include the mammary gland. One study reported an increased incidence of breast cancer in a cohort of workers who used ethylene oxide as a sterilant (Norman et al. 1995).
Citations to review sources and individual studies reporting mammary gland tumors are listed below.
Citation
Source Type
Notes
International Agency for Research on Cancer, Monographs on the evaluation of carcinogenic risk of chemicals to man. VOL.: 60 (1994) (p. 73) Ethylene oxide.
Review
mice inhalation produced mammary tumors. NTP TR326 1987
http://monographs.iarc.fr/ENG/Monographs/vol60/volume60.p...
Carcinogenic Potency Database 2005. Gold LS ST, Manley NB, Garfinkel GB, Ames BN. Summary Table by Chemical of Carcinogenicity Results in CPDB on 1485 Chemicals. 2005
Review
Two of four studies report mammary tumors: TR326 and Dunkelberg 1982. Two other studies did not report mammary tumors (Lynch 1984 and Snellings 1984/Garman 1985).
http://potency.berkeley.edu/pdfs/ChemicalTable.pdfpotency...
National Toxicology Program 11th Report on Carcinogens. Summary of Data Reported and Evaluation
Review
For mammary tumors refers to NTP TR326 and IARC Monograph on Industrial Chemicals in 1994 v. 60
http://ntp.niehs.nih.gov/ntp/roc/eleventh/profiles/s085et...
Dunkelberg H. Carcinogenicity of ethylene oxide and 1,2-propylene oxide upon intragastric administration to rats. Br J Cancer 1982;46(6):924-33.
Primary Literature

experimental details
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.
National Toxicology Program Technical Report 326, 1987
Primary Literature

experimental details
Malignant mammary tumors increased in female mice, greater at low dose. Female mice: 1/50, 8/50, 6/50 Carcinogenicity refs: Dunkelberg 1982 and 1981, Walpole 1958 (only 12 rats), Snellings 1984, Garman 1985, Lynch 1983 and 1984, NTP TR326 evaluated the Dunkelberg study and only highlighted the stomach tumors, saying "the incidence of tumors in other organs were similar in dosed and control rats"
http://ntp.niehs.nih.gov/index.cfm?objectid=03F0D5AC-FE20...
Garman RH, Snellings WM, Maronpot RR. Brain tumors in F344 rats associated with chronic inhalation exposure to ethylene oxide. Neurotoxicology 1985;6(1):117-37.
Primary Literature
CPDB combines the data of this with the Snellings paper- an update or modification. A study listed by CPDB 2005 that did not report mammary tumors. Brain tumors were the examined endpoint.
Lynch DW, Lewis TR, Moorman WJ, Burg JR, Groth DH, Khan A, et al. Carcinogenic and toxicologic effects of inhaled ethylene oxide and propylene oxide in F344 rats. Toxicol Appl Pharmacol 1984;76(1):69-84.
Primary Literature
A study listed by CPDB 2005 that did not report mammary tumors. Not focused on one particular endpoint, but only uses male rats. Same route, same time period as NTP, higher doses- up to 300 ppm. Mortality was increased in dosed animals.
Snellings WM, Weil CS, Maronpot RR. A two-year inhalation study of the carcinogenic potential of ethylene oxide in Fischer 344 rats. Toxicol Appl Pharmacol 1984;75(1):105-17.
Primary Literature
A study listed by CPDB 2005 that did not report mammary tumors. From abstract, it seems that this study could have picked up mammary tumors. They were not focused on one particular endpoint. The dosing level was similar, as was the exposure time, and the route. A marked difference was a significant depression of body weight gain in the 33ppm and 100ppm groups.