Associations between exposure to ethylene oxide, job termination, and cause-specific mortality risk

Previous analyses of mortality were conducted in a large cohort of ethylene oxide (EtO) exposed workers employed at 13 sterilization facilities throughout the U.S. and followed from the start of operation through 1998. Statistically significant elevated mortality was reported from hematopoietic cancer in men and breast cancer in women compared to the general population. Possible healthy worker survivor bias was not addressed.

To examine survivor bias in this cohort, employment termination was analyzed with statistical models stratified on sex and race that included age, employment duration, and cumulative EtO exposure. To reduce survivor bias employment duration was included in Poisson regression model specifications for estimating standardized mortality ratios for several cancer outcomes.

Strong statistically significant effects of unlagged cumulative EtO exposure were observed on rate of employment termination, indicating potential healthy worker survivor effect bias. Adjustment for employment duration in analyses of mortality resulted in statistically significant and stronger associations between cumulative EtO exposure and lung cancer, female breast cancer and hematopoietic cancer. There was a striking reduction in nonmalignant respiratory disease mortality risk with increasing employment duration with a further (nonsignificant) reduction with cumulative EtO, suggesting that EtO itself is driving termination of workers with respiratory morbidity even though the average EtO exposures in this population were generally far below odor and acute irritancy thresholds.

Important survivor bias was present in this EtO cohort and may be present in many occupational settings involving irritant exposures.