Reevaluation of Historical Exposures to Ethylene Oxide Among U.S. Sterilization Workers in the National Institute of Occupational Safety and Health (NIOSH) Study Cohort

Abstract

The 2016 U.S. Environmental Protection Agency (EPA) Integrated Risk Information System (IRIS) assessment for ethylene oxide (EO) estimated a 10^-6 increased inhalation cancer risk of 0.1 parts per trillion, based on National Institute of Occupational Safety and Health (NIOSH) epidemiology studies of sterilization facility workers exposed to EO between 1938 and 1986. The worker exposure estimates were based on a NIOSH statistical regression (NSR) model "validated" with EO levels measured after 1978. Between 1938 and 1978, when EO data was unavailable, the NSR model predicts exposures lowest in 1938 increasing to peak levels in 1978. That increasing EO concentration trend arose, in part, because engineering/industrial-hygiene (E/IH) factors associated with evolving EO-sterilization equipment and operations before 1978 were not properly considered in the NSR model. To test the NSR model trend prediction, a new E/IH-based model was developed using historical data on EO kill concentrations, EO residue levels in sterilized materials, post-wash EO concentrations in a sterilization chamber, and information on facility characteristics and sterilizer operator practices from operators familiar with pre-1978 industry conditions. The E/IH 90th percentile of 8 h time-weighted average EO exposures (C₉₀) for highly exposed sterilizer operators was calibrated to match 1978 C₉₀ values from the NSR model. E/IH model C₉₀ exposures were estimated to decrease over time from levels 16 and were four-fold greater than NSR-estimated exposures for workers during 1938-1954 and 1955-1964. This E/IH modeled trend is opposite to that of NSR model predictions of exposures before 1978, suggesting that EPA's exclusive reliance on the NIOSH cohort to estimate EO cancer risk should be re-examined.

Keywords: cancer risk; ethylene oxide; historical occupational exposure; industrial hygiene; sterilization facilities.

Figure 1

National Institute of Occupational Safety and Health (NIOSH) statistical regression (NSR) exposure model predictions of historical 90th percentile 8-h time-weighted average (TWA) occupational ethylene oxide (EO) concentration (C₉₀) during 1936–1986, specific to all facilities and job categories addressed by that model. Nearly all of the facilities sterilized medical/health products. The NSR model predicts that C₉₀ = 47.4, 30.0, and 11.9 ppm in 1978, 1959, and 1949, respectively, and predicts TWA C₉₀ values of 34.3, 27.5, and 15.9 ppm during the late, middle, and early periods defined for the present study, respectively.

Figure 2

Engineering/industrial-hygiene (E/IH) model of occupational respiratory exposure to EO used to sterilize (A) medical/health products during the Late Period and (B) medical/health products during the Early and Middle periods, and spices during the Late Period.

Figure 3

Empirical cumulative distribution of the subset of air exchange rate (AER) values reported for sterilization rooms in the spice sterilization facilities listed in Appendix C-10 of Goldgraben and Zank [16], for which AER ≤ 4/h, representative of sterilization rooms assumed not to have used forced-air ventilation. The data are consistent with an approximately uniform AER distribution between 0.25 and 4 per hour, as assessed (p = 0.52) by the Kolmogorov one sample test [26].

Figure 4

Fifty-five measures (open points) of TWA EO concentration made around sterilization chambers in the spice sterilization facilities listed and cited by Goldgraben and Zank [16], in relation to corresponding reported durations (t, in min) over which these measurements were made. The straight line shows the corresponding unweighted log–log linear regression fit to these data, EO_TWA = 419.65(t/min)^−0.7592 ppm (p = ~0, R² = 0.60), which predicts an 8 h TWA EO concentration of approximately 3.9 ppm.

Figure 5

Comparison of E/IH (thick lines) and NSR (thin lines) exposure model estimates of occupational respiratory exposures to EO in facilities that sterilized medical/health products and prevailing ACGIH TLV limits for EO (dashed lines). Shaded area represents the period during which very limited or (pre-1976) no contemporaneous measurements were available to validate NSR model predictions and during which no EO-specific regulations were in place to limit occupational EO exposures.