Ethylene Oxide: Cancer Evidence Integration and Dose–Response Implications
| Autor: | Elizabeth A. Best, Melissa J. Vincent, G. Scott Dotson, Kenneth A. Mundt, Andrew Maier, Jordan Kozal, William J. Thompson |
|---|---|
| Jazyk: | angličtina |
| Rok vydání: | 2019 |
| Předmět: |
Oncology
medicine.medical_specialty chemical Health Toxicology and Mutagenesis Review 010501 environmental sciences Toxicology Tumor response 01 natural sciences 03 medical and health sciences Animal data 0302 clinical medicine Internal medicine dose response medicine cancer 030212 general & internal medicine Carcinogen 0105 earth and related environmental sciences Chemical Health and Safety business.industry lcsh:RM1-950 Low dose Public Health Environmental and Occupational Health Cancer modeling medicine.disease lcsh:Therapeutics. Pharmacology Increased risk business Mammary Cancers International agency |
| Zdroj: | Dose-Response Dose-Response, Vol 17 (2019) |
| ISSN: | 1559-3258 |
| Popis: | 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. |
| Databáze: | OpenAIRE |
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