Review Article

Ethylene Oxide Exposure and Its Impact on Stroke Risk and All-Cause Mortality: A Population-Based Analysis

Abstract

Background: Ethylene oxide (EO) is widely used in various industries and has been associated with multiple health risks. However, its impact on stroke risk and all-cause mortality in the general population remains has not been definitively established. This study aimed to investigate the association between EO exposure, stroke risk, and all-cause mortality in a population-based sample.
Methods: Data were obtained from the National Health and Nutrition Examination Survey (NHANES) from 2013 to 2018, involving 29,350 participants. After applying inclusion and exclusion criteria, 4,908 participants with detectable EO levels and complete stroke and mortality data were included in the analysis. Hemoglobin adducts of EO (HbEO) were used as a marker of exposure. Logistic regression models were used to examine the association between EO levels and stroke risk, while Cox proportional hazards models assessed the relationship between EO levels and all-cause mortality, adjusting for covariates such as age, high blood pressure, diabetes, and smoking history.
Results: Higher EO exposure levels were significantly associated with an increased risk of stroke, particularly after adjusting for covariates such as age (OR: 1.002, 95% CI: 1.001-1.003, P<0.0001) and additional covariates (OR: 1.001, 95% CI: 1.000-1.003, P=0.023). Higher EO levels were also associated with increased all-cause mortality when adjusted for age and additional covariates (HR: 1.333, 95% CI: 1.003-1.770, P=0.047).
Conclusion: This study provides evidence of a significant association between EO exposure and increased risks of stroke and all-cause mortality in the general population. Further research is necessary to confirm these findings using direct EO exposure measurements.

1. Campbell BCV, Khatri P. (2020). Stroke. The Lancet, 396(10244): 129–42.
2. Shintani H. (2017). Ethylene Oxide Gas Sterilization of Medical Devices. Biocon-trol Sci, 22(1): 1–16.
3. Bolognesi C, Bruzzone M, Ceppi M, et al (2017). The lymphocyte cytokinesis block micronucleus test in human popu-lations occupationally exposed to vinyl chloride: A systematic review and meta-analysis. Mutat Res Rev Mutat Res, 774: 1–11.
4. Jinot J, Fritz JM, Vulimiri SV, et al (2018). Carcinogenicity of ethylene oxide: key findings and scientific issues. Toxicol Mech Methods, 28(5): 386–96.
5. Marsh GM, Keeton KA, Riordan AS, et al (2019). Ethylene oxide and risk of lym-pho-hematopoietic cancer and breast cancer: a systematic literature review and meta-analysis. Int Arch Occup Environ Health, 92(7): 919–39.
6. Ohnishi A, Murai Y. (1994). Polyneuropathy Due to Ethylene Oxide, Propylene Ox-ide, and Butylene Oxide. In: Araki S. Neurobehavioral Methods and Effects in Occu-pational and Environmental Health. 1st ed. Academic Press, pp. 937–42.
7. O'Kelley L, Swanson B, Bishop‐Royse JC. (2023). Integrative literature review: Eth-ylene oxide exposure signs and symp-toms. Public Health Nurs, 40(5): 790–809.
8. Ogawa M, Oyama T, Isse T, et al (2006). Hemoglobin Adducts as a Marker of Exposure to Chemical Substances, Espe-cially PRTR Class I Designated Chemi-cal Substances. J Occup Health, 48(5): 314–28.
9. Li Z, Shi P, Chen Z, et al (2023). The asso-ciation between ethylene oxide exposure and asthma risk: a population-based study. Environ Sci Pollut Res Int, 30(9): 24154–67.
10. Song W, Hu H, Ni J, et al (2023). The rela-tionship between ethylene oxide levels in hemoglobin and the prevalence of kidney stones in US adults: an exposure–response analysis from NHANES 2013–2016. Environ Sci Pollut Res, 30(10): 26357–66.
11. Zhu X, Kong X, Chen M, et al (2022). Blood ethylene oxide, systemic inflam-mation, and serum lipid profiles: Results from NHANES 2013–2016. Chemosphere, 299: 134336.
12. Prevention, C. L. P. (2012). US department of health and human services centers for disease control and prevention. Na-tional Center for Environmental Health, US. Available from: https://www.cdc.gov/nceh/index.html
13. Swenberg JA, Lu K, Moeller BC, et al (2011). Endogenous versus exogenous DNA adducts: their role in carcinogenesis, ep-idemiology, and risk assessment. Toxicol Sci, 120 Suppl 1(Suppl 1): S130–45.
14. Kirman C, Li A, Sheehan P, et al (2021). Ethylene oxide review: characterization of total exposure via endogenous and exogenous pathways and their implica-tions to risk assessment and risk man-agement. J Toxicol Environ Health, Part B, 24(1): 1–29.
15. Olaguer EP, Robinson A, Kilmer S, et al (2020). Ethylene oxide exposure attribu-tion and emissions quantification based on ambient air measurements near a sterilization facility. Int J Environ Res Public Health, 17(1): 42.
16. Hogstedt C, Rohlén O, Berndtsson BS, et al (1979). A cohort study of mortality and cancer incidence in ethylene oxide pro-duction workers. Br J Ind Med, 36(4): 276-80.
17. Zeng G, Zhang Q, Wang X, et al (2021). As-sociation between blood ethylene oxide levels and the risk of cardiovascular dis-eases in the general population. Environ Sci Pollut Res, 28(45): 64921–8.
18. Andrews JE, Courtney KD, Donaldson W (1983). The effects of ethylene chloro-hydrin on fatty acid synthesis. J Environ Sci Health Part B, 18(3): 351–67.
19. Katoh T, Higashi K, Inoue N, et al (1990). Different responses of cytosolic and mitochondrial glutathione in rat livers after ethylene oxide exposure. Toxicol Lett, 54(2–3): 235–9.
20. Tangvarasittichai S. (2015). Oxidative stress, insulin resistance, dyslipidemia and type 2 diabetes mellitus. World J Diabetes, 6(3): 456-80.
21. Orellana-Urzúa S, Rojas I, Líbano L, et al (2020). Pathophysiology of Ischemic Stroke: Role of Oxidative Stress. Curr Pharm Des, 26(34): 4246–60.
22. Mahemuti N, Jing X, Zhang N, et al (2023). Association between Systemic Immuni-ty-Inflammation Index and Hyper-lipidemia: A Population-Based Study from the NHANES (2015–2020). Nu-trients, 15(5) : 1177.
23. Papoutsidakis N, Deftereos S, Giannopou-los G, et al (2014). Treating dyslipidemi-as: is inflammation the missing link? Med Chem, 10(7): 643–52.
24. Ulrich CE, Geil RG, Tyler TR, et al (1992). Two-week aerosol inhalation study in rats of ethylene oxide/propylene oxide copolymers. Drug Chem Toxicol, 15(1): 15–31.
25. Esteve E, Ricart W, Fernandez-Real JM. (2005). Dyslipidemia and inflammation: an evolutionary conserved mechanism. Clin Nutr, 24(1): 16–31.
26. Guo J, Wan Z, Cui G, et al (2021). Associa-tion of exposure to ethylene oxides with risk of diabetes mellitus: results from NHANES 2013–2016. Environ Sci Pollut Res, 28: 68551–9.
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IssueVol 54 No 8 (2025) QRcode
SectionReview Article(s)
DOI https://doi.org/10.18502/ijph.v54i8.19572
Keywords
Stroke All-cause mortality Ethylene oxide

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How to Cite
1.
Li C, Qi C, He Y, Fan B, Bai R. Ethylene Oxide Exposure and Its Impact on Stroke Risk and All-Cause Mortality: A Population-Based Analysis. Iran J Public Health. 2025;54(8):1631-1642.