Use of updated mortality study of ethylene oxide manufacturing workers to inform cancer risk assessment

The two most recent cancer risk assessments for ethylene oxide (EO) are based on the same epidemiologic study of sterilant workers conducted by the National Institute of Occupational Safety and Health (NIOSH) but result in cancer risk estimates with three orders of magnitude difference, despite relying on the same assumption of a default linear (non-threshold) extrapolation. A major reason for the difference is the use of different exposure-response models (i.e., the standard Cox proportional hazards [CPH] versus a two-piece linear spline model with a steep initial slope) to derive the inhalation unit risk. The purpose of this research is to utilize analysis of a 10-year update of the Union Carbide Corporation (UCC) EO 2053 chemical worker cohort to examine the epidemiological evidence for the shape of the exposure-response model for EO. This updated UCC study provides an external dataset that is informative given high average cumulative exposures (67 ppm-years), extensive average follow-up of over 40 years, and number of male lymphoid cancer deaths (25) comparable to that observed in the NIOSH cohort. This independent analysis of a different cohort using continuous dose response modeling with cumulative or log cumulative exposure metrics provides no empirical support for a steep curve at low exposures. Furthermore, analyses of the categorical odds ratio estimates across different updates of the UCC cohort and for each sex in the NIOSH cohort provide further epidemiological evidence that the standard CPH model more plausibly describes the relationship between EO exposures and lymphoid mortality for both cohorts.