Carcinogenicity of ethylene oxide: key findings and scientific issues

Abstract

In support of the Integrated Risk Information System (IRIS), the U.S. Environmental Protection Agency (EPA) completed an evaluation of the inhalation carcinogenicity of ethylene oxide (EtO) in December 2016. This article reviews key findings and scientific issues regarding the carcinogenicity of EtO in EPA’s Carcinogenicity Assessment. EPA’s assessment critically reviewed and characterized epidemiologic, laboratory animal, and mechanistic studies pertaining to the human carcinogenicity of EtO, and addressed some key scientific issues such as the analysis of mechanistic data as part of the cancer hazard evaluation and to inform the quantitative risk assessment. The weight of evidence from the epidemiologic, laboratory animal, and mechanistic studies supports a conclusion that EtO is carcinogenic in humans, with the strongest human evidence linking EtO exposure to lymphoid and breast cancers. Analyses of the mechanistic data establish a key role for genotoxicity and mutagenicity in EtO-induced carcinogenicity and reveal little evidence supporting other mode-of-action hypotheses. In conclusion, EtO was found to be carcinogenic to humans by inhalation, posing a potential human health hazard for lymphoid and breast cancers.

Keywords:

• Assessment
• cancer/tumors
• breast cancer
• epidemiology
• review
• integrated risk information system
• mode of action
• ethylene oxide
• mutagenesis
• genotoxicity

Acknowledgements

This work has benefitted from comments from a number of scientific reviewers, including members of two EPA Science Advisory Board review panels, scientists at various federal agencies (including EPA), and scientists who prepared public comments. We also thank D. Bussard, P. White, and V. Morozov for providing EPA management support for the assessment and this manuscript and David DeMarini and Anu Mudipalli for their technical review of a draft manuscript.

Disclosure statement

No potential conflict of interest was reported by the authors. The views expressed in this article are those of the authors and do not necessarily represent the views or policies of the U.S. Environmental Protection Agency.