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2025
Environ Health Perspect
An updated analysis of the largest cohort of ethylene oxide (EtO)-exposed workers—7,549 women employed ≥1 year at 13 U.S. facilities followed from 1960-2021 (181 breast cancer deaths)—found that cumulative EtO exposure was strongly associated with elevated breast cancer mortality, with workers accruing 3,650 ppm-days of exposure (equivalent to 10 years at 1 ppm) having over three times the breast cancer death rate compared to unexposed workers (RR = 3.15; 95% CI: 1.78-5.60) using a 20-year lag model. This association remained robust in a subcohort with interview data on breast cancer risk factors after matching on potential confounders (RR = 3.22; 95% CI: 1.52-7.13), with evidence of variation by time since exposure and exposure rate. These findings provide strong evidence that EtO is a human breast carcinogen and support recent emission reduction proposals, raising serious public health concerns given the high prevalence of breast cancer, large numbers of occupationally exposed workers, and potential for widespread environmental exposure from industrial facilities, with elevated risks observed even in low exposure ranges highlighting the need for stringent exposure controls and environmental monitoring.
2023
J Natl Cancer Inst
A large cohort study of 451,945 National Institutes of Health-AARP Diet and Health Study participants used EPA Toxics Release Inventory data to estimate historical environmental ethylene oxide (EtO) exposures based on proximity to EtO-emitting facilities, wind patterns, and emission levels from enrollment in 1995-1996. Among 173,670 postmenopausal women, living within 10 km of EtO facilities was associated with statistically significant breast cancer risk for invasive disease (HR = 1.03; 95% CI: 0.97-1.09); women in the highest quartile of the airborne emissions index showed elevated risk of in situ breast cancer at 10 km (HR = 1.25; 95% CI: 1.02-1.53), with no clear patterns for non-Hodgkin lymphoma risk. These findings reveal a novel potential association between environmental EtO exposure and in situ breast cancer—but not invasive breast cancer or lymphohematopoietic cancers—contrasting with occupational studies that found associations with invasive disease. The differential association with in situ versus invasive disease suggests EtO may influence early-stage breast carcinogenesis, though the mechanism remains unclear and warrants further investigation to understand why environmental exposures show different patterns than occupational exposures and why the effect appears limited to pre-invasive lesions.
2019
Int Arch Occup Environ Health
A systematic review and meta-analysis of 30 studies (with meta-analyses conducted on 13 studies) examined the association between occupational ethylene oxide (EO) exposure and risk of lympho-hematopoietic cancers (LHC) and breast cancer. The overall pooled meta-relative risk was 1.48 (95% CI: 1.07-2.05) for LHC and 0.97 (95% CI: 0.80-1.18) for breast cancer, with meta-RRs for LHC among EO production workers at 1.46 and sterilization workers at 1.07, neither reaching statistical significance. Notably, a clear temporal trend emerged showing substantially higher LHC risk estimates in earlier studies from the 1980s (meta-RR = 3.87) that progressively declined in more recent decades, with studies from the 2000s and 2010s showing meta-RRs of 1.05 and 1.19 respectively, neither statistically significant. The authors conclude that the most informative and methodologically rigorous epidemiological studies published in recent decades do not support an association between occupational ethylene oxide exposure and increased risk of either lympho-hematopoietic cancers or breast cancer, suggesting that earlier positive findings may have been influenced by methodological limitations, exposure misclassification, or confounding factors that have been better controlled in more recent research.
2014
Environ Health Perspect
This review of exposure biomarkers for chemicals potentially linked to breast cancer identified methods for 102 chemicals causing mammary tumors in rodents, finding biomarkers for nearly 75% of them, with human exposure biomarkers existing for 62 chemicals (45 measured in non-occupationally exposed populations) and the CDC tracking 23 of them. Among rodent mammary carcinogens with >50% population detection frequency were PAHs (98%), methyleugenol (98%), PFOA (>50%), chlordane (>50%), acrylamide (>50%), and benzene (>50%), indicating near-universal exposure to multiple mammary carcinogens, with several additional chemicals showing >50% detection of urinary metabolites including ethylene oxide, acrylonitrile, fenvalerate, and vinyl chloride (71-75%). The study found consistent carcinogenicity between humans and rodents for many chemicals, though limited data exists for direct effects in humans, and emphasizes the availability of biomonitoring tools and resources to advance breast cancer prevention efforts. The findings underscore that populations are ubiquitously exposed to multiple known mammary carcinogens simultaneously, highlighting the urgent need for biomonitoring programs to assess mixed exposures and inform prevention strategies targeting modifiable environmental risk factors for breast cancer.