Carcinogenicity of ethylene oxide: key findings and scientific issues

References

• Adám B, Bárdos H, Adány R. 2005. Increased genotoxic susceptibility of breast epithelial cells to ethylene oxide. Mutat Res. 585:120–126.
   PubMed Web of Science ®Google Scholar
• Boffetta P, van der Hel O, Norppa H, Fabianova E, Fucic A, Gundy S, Lazutka J, Cebulska-Wasilewska A, Puskailerova D, Znaor A, et al. 2007. Chromosomal aberrations and cancer risk: results of a cohort study from Central Europe. Am J Epidemiol. 165:36–43.
   PubMed Web of Science ®Google Scholar
• Bonassi S, Znaor A, Ceppi M, Lando C, Chang WP, Holland N, Kirsch-Volders M, Zeiger E, Ban S, Barale R, et al. 2007. An increased micronucleus frequency in peripheral blood lymphocytes predicts the risk of cancer in humans. Carcinogenesis. 28:625–631.
   PubMed Web of Science ®Google Scholar
• Brown CD, Wong BA, Fennell TR. 1996. In vivo and in vitro kinetics of ethylene oxide metabolism in rats and mice. Toxicol Appl Pharmacol. 136:8–19.
   PubMed Web of Science ®Google Scholar
• DeMarini DM. 2000. Influence of DNA repair on mutation spectra in Salmonella. Mutat Res. 450:5–17.
   PubMed Web of Science ®Google Scholar
• Fennell TR, Brown CD. 2001. A physiologically based pharmacokinetic model for ethylene oxide in mouse, rat, and human. Toxicol Appl Pharmacol. 173:161–175.
   PubMed Web of Science ®Google Scholar
• Garman RH, Snellings WM, Maronpot RR. 1985. Brain tumors in F344 rats associated with chronic inhalation exposure to ethylene oxide. Neurotoxicology. 6:117–137.
   PubMed Web of Science ®Google Scholar
• Garman RH, Snellings WM, Maronpot RR. 1986. Frequency, size and location of brain tumours in F-344 rats chronically exposed to ethylene oxide. Food Chem Toxicol. 24:145–153.
   PubMed Web of Science ®Google Scholar
• Godderis L, Aka P, Matecuca R, Kirsch-Volders M, Lison D, Veulemans H. 2006. Dose-dependent influence of genetic polymorphisms on DNA damage induced by styrene oxide, ethylene oxide and gamma-radiation. Toxicology. 219:220–229.
   PubMed Web of Science ®Google Scholar
• Greife AL, Hornung RW, Stayner LG, Steenland KN. 1988. Development of a model for use in estimating exposure to ethylene oxide in a retrospective cohort mortality study. Scand J Work Environ Health. 1:29–30.
   Google Scholar
• Hagmar L, Strömberg U, Bonassi S, Hansteen IL, Knudsen LE, Lindholm C, Norppa H. 2004. Impact of types of lymphocyte chromosomal aberrations on human cancer risk: results from Nordic and Italian cohorts. Cancer Res. 64:2258–2263.
   PubMed Web of Science ®Google Scholar
• Hill AB. 1965. The environment and disease: Association or causation? Proc R Soc Med. 58:295–300.
   PubMed Web of Science ®Google Scholar
• Högstedt B, Gullberg B, Hedner K, Kolnig A-M, Mitelman F, Skerfving S, Widegren B. 1983. Chromosome aberrations and micronuclei in bone marrow cells and peripheral blood lymphocytes in humans exposed to ethylene oxide. Hereditas. 98:105–113.
   PubMed Web of Science ®Google Scholar
• Hong H-HL, Houle CD, Ton T, -VT, Sills RC. 2007. K-ras mutations in lung tumors and tumors from other organs are consistent with a common mechanism of ethylene oxide tumorigenesis in the B6C3F1 mouse. Toxicol Pathol. 35:81–85.
   PubMed Web of Science ®Google Scholar
• Hornung RW, Greife AL, Stayner LT, Steenland NK, Herrick RF, Elliott LJ, Ringenburg VL, Morawetz J. 1994. Statistical model for prediction of retrospective exposure to ethylene oxide in an occupational mortality study. Am J Ind Med. 25:825–836.
   PubMed Web of Science ®Google Scholar
• Houle CD, Ton T, -VT, Clayton N, Huff J, Hong H, -HL, Sills RC. 2006. Frequent p53 and H-ras mutations in benzene- and ethylene oxide-induced mammary gland carcinomas from B6C3F1 mice. Toxicol Pathol. 34:752–762.
   PubMed Web of Science ®Google Scholar
• IARC. 2008. Ethylene oxide. (IARC monographs on the evaluation of carcinogenic risks to humans: Volume 97, 1,3-butadiene, ethylene oxide and vinyl halides (vinyl fluoride, vinyl chloride and vinyl bromide)). Lyon, France.
   Google Scholar
• IARC. 2012. Ethylene oxide. IARC monographs on the evaluation of carcinogenic risks to humans. Volume 100F: Chemical agents and related occupations. Lyon, France, World Health Organization.
   Google Scholar
• Kardos L, Széles G, Gombkötö G, Szeremi M, Tompa A, Ádány R. 2003. Cancer deaths among hospital staff potentially exposed to ethylene oxide: An epidemiological analysis. Environ Mol Mutagen. 42:59–60.
   PubMed Web of Science ®Google Scholar
• Kirman CR, Sweeney LM, Teta MJ, Sielken RL, Valdez-Flores C, Albertini RJ, Gargas ML. 2004. Addressing nonlinearity in the exposure–response relationship for a genotoxic carcinogen: Cancer potency estimates for ethylene oxide. Risk Anal. 24:1165–1183.
   PubMed Web of Science ®Google Scholar
• Lynch DW, Lewis TR, Moorman WJ, Burg JR, Groth DH, Khan A, Ackerman LJ, Cockrell BY. 1984. Carcinogenic and toxicologic effects of inhaled ethylene oxide and propylene oxide in F344 rats. Toxicol Appl Pharmacol. 76:69–84.
   PubMed Web of Science ®Google Scholar
• Marsden DA, Jones DJ, Britton RG, Ognibene T, Ubick E, Johnson GE, Farmer PB, Brown K. 2009. Dose–response relationships for N7-(2-hydroxyethyl)guanine induced by low-dose [14C]ethylene oxide: Evidence for a novel mechanism of endogenous adduct formation. Cancer Res. 69:3052–3059.
   PubMed Web of Science ®Google Scholar
• Mikoczy Z, Tinnerberg H, Björk J, Albin M. 2011. Cancer incidence and mortality in Swedish sterilant workers exposed to ethylene oxide: Updated cohort study findings 1972-2006. Int J Environ Res Public Health. 8:2009–2019.
   PubMed Web of Science ®Google Scholar
• Nagy K, Ádány R, Szűcs S, Ádám B. 2013. Susceptibility of lung epithelial cells to alkylating genotoxic insult. Environ Mol Mutagen. 54:682–689.
   PubMed Web of Science ®Google Scholar
• Norman SA, Berlin JA, Soper KA, Middendorf BF, Stolley PD. 1995. Cancer incidence in a group of workers potentially exposed to ethylene oxide. Int J Epidemiol. 24:276–284.
   PubMed Web of Science ®Google Scholar
• NTP. 1987. Toxicology and carcinogenesis studies of ethylene oxide (CAS no 75-21-8) in B6C3F1 mice (inhalation studies). Natl Toxicol Program Tech Rep Ser. 326:1–114.
   PubMedGoogle Scholar
• NTP. 1999. Report on carcinogens (9th): 1999, Full report. Research Triangle Park, NC.
   Google Scholar
• Parsons BL, Manjanatha MG, Myers MB, McKim KL, Shelton SD, Wang Y, Gollapudi BB, Moore NP, Haber LT, Moore MM. 2013. Temporal changes in K-ras mutant fraction in lung tissue of big blue B6C3F1 mice exposed to ethylene oxide. Toxicol Sci. 136:26–38.
   PubMed Web of Science ®Google Scholar
• SAB. 2007. Review of Office of Research and Development (ORD) draft assessment entitled “Evaluation of the carcinogenicity of ethylene oxide”. Washington, DC, U.S. Environmental Protection Agency, Science Advisory Board.
   Google Scholar
• SAB. 2015. Science Advisory Board Review of the EPAs evaluation of the inhalation carcinogenicity of ethylene oxide: Revised external review draft – August 2014. EPA-SAB-15-012. Washington, DC, U.S. Environmental Protection Agency, Science Advisory Board.
   Google Scholar
• Smith MT, Guyton KZ, Gibbons CF, Fritz JM, Portier CJ, Rusyn I, DeMarini DM, Caldwell JC, Kavlock RJ, Lambert PF, et al. 2016. Key characteristics of carcinogens as a basis for organizing data on mechanisms of carcinogenesis. Environ Health Perspect. 124:713–721.
   PubMed Web of Science ®Google Scholar
• Snellings WM, Weil CS, Maronpot RR. 1984. A two-year inhalation study of the carcinogenic potential of ethylene oxide in Fischer 344 rats. Toxicol Appl Pharmacol. 75:105–117.
   PubMed Web of Science ®Google Scholar
• Steenland K, Stayner L, Greife A, Halperin W, Hayes R, Hornung R, Nowlin S. 1991. Mortality among workers exposed to ethylene oxide. N Engl J Med. 324:1402–1407.
   PubMed Web of Science ®Google Scholar
• Steenland K, Whelan E, Deddens J, Stayner L, Ward E. 2003. Ethylene oxide and breast cancer incidence in a cohort study of 7576 women (United States). Cancer Causes Control. 14:531–539.
   PubMed Web of Science ®Google Scholar
• Steenland K, Stayner L, Deddens J. 2004. Mortality analyses in a cohort of 18 235 ethylene oxide exposed workers: Follow up extended from 1987 to 1998. Occup Environ Med. 61:2–7.
   PubMed Web of Science ®Google Scholar
• Swaen GMH, Burns C, Teta JM, Bodner K, Keenan D, Bodnar CM. 2009. Mortality study update of ethylene oxide workers in chemical manufacturing: A 15 year update. J Occup Environ Med. 51:714–723.
   PubMed Web of Science ®Google Scholar
• Tates AD, Grummt T, Törnqvist M, Farmer PB, van Dam FJ, van Mossel H, Schoemaker HM, Osterman-Golkar S, Uebel C, Tang YS. 1991. Biological and chemical monitoring of occupational exposure to ethylene oxide. Mutat Res. 250:483–497.
   PubMed Web of Science ®Google Scholar
• Tompkins EM, Jones DJL, Lamb JH, Marsden DA, Farmer PB, Brown K. 2008. Simultaneous detection of five different 2-hydroxyethyl-DNA adducts formed by ethylene oxide exposure, using a high-performance liquid chromatography/electrospray ionisation tandem mass spectrometry assay. Rapid Commun Mass Spectrom. 22:19–28.
   PubMed Web of Science ®Google Scholar
• U.S. EPA. 1997. Chemical and radiation leukemogenesis in humans and rodents and the value of rodent models for assessing risks of lymphohematopoietic cancers. EPA/600/R-97/090. Washington, DC, Office of Research and Development, National Center for Environmental Assessment.
   Google Scholar
• U.S. EPA. 2005a. Guidelines for carcinogen risk assessment. EPA/630/P-03/001F. Washington, DC, U.S. Environmental Protection Agency, Risk Assessment Forum.
   Google Scholar
• U.S. EPA. 2005b. Supplemental guidance for assessing susceptibility from early-life exposure to carcinogens. EPA/630/R-03/003F. Washington, DC, U.S. Environmental Protection Agency, Risk Assessment Forum.
   Google Scholar
• U.S. EPA. 2016a. Evaluation of the inhalation carcinogenicity of ethylene oxide (CASRN 75-21-8): In support of summary information on the Integrated Risk Information System (IRIS). EPA/635/R-16/350Fa. Washington, DC, U.S. Environmental Protection Agency, Office of Research and Development, National Center for Environmental Assessment.
   Google Scholar
• U.S. EPA. 2016b. Evaluation of the inhalation carcinogenicity of ethylene oxide – appendices (CASRN 75-21-8): In support of summary information on the Integrated Risk Information System (IRIS). EPA/635/R-16/350Fb. Washington, DC, U.S. Environmental Protection Agency, Office of Research and Development, National Center for Environmental Assessment.
   Google Scholar
• U.S. EPA. 2017. TRI Explorer (2015 dataset released October 2016). Washington, DC.
   Google Scholar
• Walker VE, Fennell TR, Upton PB, Skopek TR, Prevost V, Shuker DEG, Swenberg JA. 1992a. Molecular dosimetry of ethylene oxide: formation and persistence of 7-(2-hydroxyethyl)guanine in DNA following repeated exposures of rats and mice. Cancer Res. 52:4328–4334.
   PubMed Web of Science ®Google Scholar
• Walker VE, MacNeela JP, Swenberg JA, Turner MJ, Jr, Fennell TR. 1992b. Molecular dosimetry of ethylene oxide: formation and persistence of N-(2-hydroxyethyl)valine in hemoglobin following repeated exposures of rats and mice. Cancer Res. 52:4320–4327.
   PubMed Web of Science ®Google Scholar
• Zhang F, Bartels MJ, LeBaron MJ, Schisler MR, Gollapudi BB, Moore NP. 2015a. A novel approach for concurrent quantitation of glutathione, glutathione disulfide, and 2-hydroxyethylated glutathione in lungs of mice exposed to ethylene oxide, using liquid chromatography-positive electrospray tandem mass spectrometry. Biomed Chromatogr. 29:1364–1374.
   PubMed Web of Science ®Google Scholar
• Zhang F, Bartels MJ, LeBaron MJ, Schisler MR, Jeong Y-C, Gollapudi BB, Moore NP. 2015b. LC-MS/MS simultaneous quantitation of 2-hydroxyethylated, oxidative, and unmodified DNA nucleosides in DNA isolated from tissues of mice after exposure to ethylene oxide. J Chromatogr B Analyt Technol Biomed Life Sci. 976–977:33–48.
   PubMed Web of Science ®Google Scholar