Carcinogenicity of ethylene oxide: key findings and scientific issues

• Published in: Toxicology mechanisms and methods Vol. 28; no. 5; pp. 386 - 396
• Main Authors: Jinot, Jennifer, Fritz, Jason M, Vulimiri, Suryanarayana V, Keshava, Nagalakshmi
• Format: Journal Article
• Language: English
• Published: England 13.06.2018
• Subjects: Animals; Breast Neoplasms - chemically induced; Breast Neoplasms - epidemiology; Breast Neoplasms - genetics; Breast Neoplasms - pathology; Carcinogenicity Tests; Carcinogens - toxicity; Cell Transformation, Neoplastic - chemically induced; Cell Transformation, Neoplastic - genetics; Cell Transformation, Neoplastic - pathology; Ethylene Oxide - toxicity; Female; Humans; Inhalation Exposure - adverse effects; Lymphoproliferative Disorders - chemically induced; Lymphoproliferative Disorders - epidemiology; Lymphoproliferative Disorders - genetics; Lymphoproliferative Disorders - pathology; Male; Models, Animal; Mutagenicity Tests; Risk Assessment; genotoxicity; epidemiology; cancer/tumors; mode of action; ethylene oxide; integrated risk information system; review; Assessment; breast cancer; mutagenesis
• ISSN: 1537-6516; 1537-6524
• DOI: 10.1080/15376516.2017.1414343

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.