Ethylene Oxide: Cancer Evidence Integration and Dose–Response Implications

Abstract

The International Agency for Research on Cancer (IARC) and the United States Environmental Protection Agency (USEPA) classified ethylene oxide (EtO) as a known human carcinogen. Critically, both noted that the epidemiological evidence based on lymphoid and breast cancers was “limited,” but that the evidence in animal studies was “sufficient” and “extensive” (respectively) and that EtO is genotoxic. The USEPA derived one of the highest published inhalation unit risk (IUR) values (3 × 10−3 per [µg/m3 EtO]), based on results from 2 epidemiological studies. We performed focused reviews of the epidemiological and toxicological evidence on the carcinogenicity of EtO and considered the USEPA’s reliance on a genotoxic mode of action to establish EtO’s carcinogenicity and to determine likely dose–response patterns. Higher quality epidemiological studies demonstrated no increased risk of breast cancers or lymphohematopoietic malignancies (LHM). Similarly, toxicological studies and studies of early effect biomarkers in animals and humans provided no strong indication that EtO causes LHM or mammary cancers. Ultimately, animal data are inadequate to define the actual dose–response shape or predict tumor response at very low doses with any confidence. We conclude that the IARC and USEPA classification of EtO as a known human carcinogen overstates the underlying evidence and that the IUR derived by USEPA grossly overestimates risk.

The role of endogenous versus exogenous sources in the exposome of putative genotoxins and consequences for risk assessment

“…The evaluations of both IARC and US-EPA are being questioned. Thus, Vincent et al (Vincent et al 2019 ) argued that higher quality epidemiological studies demonstrated no increased risk of breast cancers or lymphohaematopoietic malignancies, and that toxicological studies and studies of early effect biomarkers in animals and humans provided no strong indication that EO causes lymphohaematopoietic or mammary cancers. In consequence, animal data were addressed as being inadequate to define the actual dose–response shape or predict tumour response at very low doses with any confidence.…”

Transitioning to Environmentally Sustainable, Climate-Smart Radiation Oncology Care

“…For example, single-use supplies are often sterilized using ethylene oxide (ETO), a known carcinogen. 28 As a localized example of the adverse public health effects of medical care, Sterigenics, a medical supply sterilization facility north of Chicago, was forced to close in 2019 due to public outcry of the use of ETO gas. A recent report by the Environmental Protection Agency showed increased cancer rates in that community, validating these concerns.…”

Trace Measurements of Ethylene Oxide Using Cavity-enhanced Absorption Spectrometry near 3066 cm–1

“…After an extensive review of the available data, the US Environmental Protection Agency (EPA) Integrated Risk Information System (IRIA) program concluded (Office of Research and Development US EPA, 2016) that the "…confidence in the hazard characterization of EtO as 'carcinogenic to humans' is high." Using this data, the EPA has assigned a total cancer unit risk (inhalation unit risk) estimate for EtO of 3.3 × 10 -3 μg/m 3 (~12 ppt), though recent studies (Vincent et al, 2019;Texas Commission on Environmental Quality, 2020) suggests that this unit risk estimate may be too low and a value of ~2 ppb may be more appropriate.…”