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.

Ethylene oxide review: characterization of total exposure via endogenous and exogenous pathways and their implications to risk assessment and risk management

“…1. Recent exposure reconstruction efforts which indicate that historical worker exposures may have been considerably higher than estimated for USEPA unit risk values (Bogen et al 2019). In addition, the unit risk value should be assessed in terms of total exposures to workers, rather than relying solely on the characterization of the exogenous pathway, and include three components: (A) endogenous production; (B) exogenous occupational exposure; and (C) exogenous exposures from smoking, for which historical exposures are expected to be larger than current exposures due to changes in smoking habits (Table 7); 2.…”

“…Occupational exposures to ethylene oxide are associated with specific industries including hospital workers (Haufroid et al 2007), sterilization workers (Bogen et al 2019), chemical manufacturing workers (Swaen et al 2009;Teta, Benson, and Vitale 1993), and fruit store workers exposed to plant-produced ethylene (Tornqvist et al, 1989). An exposure reconstruction of sterilization operators exposed to ethylene oxide was recently conducted (Bogen et al 2019). Estimated historical exposures to ethylene oxide by sterilization operators are many orders of magnitude higher than those encountered today.…”

“…pre-1978 measurements are not available), predicted that exposures were lowest in 1938 and rose to peak levels in 1978. A recent analysis by Bogen et al (2019) yielded an exposure model that better accounts for engineering/industrial hygiene factors (E/IH). The E/IH-based model of Bogen et al (2019) was developed using historical data on ethylene oxide kill concentrations, residue levels in sterilized materials, post-wash concentrations in a sterilization chamber, and information on sterilizer operator practices prior to 1978.…”

Ethylene Oxide Exposure in U.S. Populations Residing Near Sterilization and Other Industrial Facilities: Context Based on Endogenous and Total Equivalent Concentration Exposures

“…In contrast, the Texas Commission on Environmental Quality (TCEQ) using the same cohort data as EPA IRIS, but a different dose-response model, estimated 10 −6 to 10 −4 RSCs of 0.24 to 24 ppb, respectively [ 6 ]. We note that neither the EPA nor TCEQ addressed the assumption of low exposure concentrations for early sterilization workers, which was shown to be invalid [ 7 ]. The EPA assessment short comings left a gap in our ability to interpret the health significance of general population exogenous EO background exposures from non-industrial and natural EO sources, and, perhaps more importantly, local general population exposures from point source industrial emissions.…”

“…More importantly, these RSCs are more than three orders of magnitude below airborne concentrations equivalent to endogenously produced EO, in the general nonsmoking population (mean concentrations of ~1.9 and 2.9 ppb) based on data evaluated by Kirman and Hays [ 2 ], based on data from published unexposed control subjects [ 8 , 9 , 10 , 11 , 12 , 13 , 14 , 15 , 16 , 17 ] and Kirman et al [ 3 ], and based on data from nonsmoking U.S. individuals [ 4 ], respectively. For additional perspective, as described by Bogen et al [ 7 ], these RSCs are up to seven orders of magnitude below the levels of EO to which 1930s–1970s sterilization operators and other highly exposed sterilization workers in the National Institute for Occupational Safety and Health (NIOSH) cohort used by EPA in its risk assessment were exposed (50,000 to >100,000 ppb). Based on these comparisons, it is obvious that the EPA RSCs are incapable of providing useful benchmarks to evaluate the health significance of such low general population EO exposures.…”