Exposure to Ethylene Oxide and Relative Rates of Female Breast Cancer Mortality: 62 Years of Follow-Up in a Large US Occupational Cohort.

Background: Ethylene oxide (EtO) is a recognized carcinogen of concern in occupational and environmental settings, but evidence of cancer risks in humans remains limited. Since new EtO emission standards and mitigation measures have been proposed, further investigation of EtO cancer risks is needed to inform quantitative risk assessment.

Objective: Our objective was to estimate the association between cumulative EtO exposure and risk of death from breast cancer.

Methods: We had data on 7,549 women from the largest cohort of EtO-exposed workers who were employed for at least 1 y at one of 13 US facilities, with mortality follow-up from 1 January 1960 to 31 December 2021. We estimated relative rates (RR) of the association between cumulative EtO exposure [parts per million days (ppm-days)] and breast cancer mortality using Cox proportional hazard models, using a matched risk-set sampling design with attained age as the underlying time scale. We further examined a subcohort of women who participated in interviews that contained information about breast cancer risk factors.

Results: Cumulative exposure to EtO was associated with elevated RRs of breast cancer mortality (181 deaths). In a log-log model with a 20-y lag fit, workers who accrued $\mathrm{3,650}\text{\hspace{0.17em}ppm-days}$ of exposure (equivalent to 10 y exposed at a rate of $1\text{\hspace{0.17em}ppm}$) had over three times the rate of breast cancer death in comparison with unexposed workers (RR at 3,650 $\text{ppm-days}=3.15$; 95% CI: 1.78, 5.60). This RR remained elevated for the subset of the cohort with interview data after matching on potential confounders (RR at 3,650 $\text{ppm-days}=3.22$; 95% CI: 1.52, 7.13). We observed evidence of variation in RRs by time since exposure and exposure rate.

Discussion: This updated analysis of an EtO-exposed worker cohort builds on evidence that EtO is a human breast carcinogen and supports recent exposure reduction proposals. Given the high prevalence of breast cancer, the large number of workers exposed to EtO and the potential for widespread environmental exposure increased risks observed even in the low exposure range are of serious public health importance. https://doi.org/10.1289/EHP15566.