In the evolving landscape of environmental health research, a groundbreaking study published in 2025 is reshaping our understanding of the intricate relationship between ethylene exposure and internal ethylene oxide formation in the human body. Ethylene oxide (EtO), a potent carcinogen recognized globally, has long been a subject of concern due to its presence in air pollution and tobacco smoke. However, emerging evidence now uncovers complex endogenous pathways that challenge previously held notions about its origins and exposures. This revelation is not only pivotal for toxicological science but also for public health policies aimed at curbing cancer risks associated with chemical exposures.
Ethylene oxide, primarily known for its industrial applications in sterilization and as a chemical intermediate, is classified as a Group 1 carcinogen by the International Agency for Research on Cancer (IARC). Its carcinogenic potential is strongly linked to inhalation of contaminated air, especially in occupational settings and urban environments with significant industrial emissions. The general population’s exposure largely arises from polluted air inhalation and cigarette smoke, both sources contributing a measurable burden of EtO. Despite this established exposure route, new research highlights an overlooked endogenous formation mechanism that complicates exposure assessment and risk evaluation.
At the heart of this discovery lies ethylene (ET), a volatile hydrocarbon that itself originates from both exogenous and endogenous processes. Ethylene is emitted into the atmosphere through combustion processes, plant metabolism, and microbial activities, rendering the human environment naturally replete with this molecule. Within the human body, however, ethylene can also be generated through lipid peroxidation—a metabolic reaction where reactive oxygen species degrade cell membrane components. This internal ethylene serves as a precursor for ethylene oxide through oxidative enzymatic pathways, suggesting that significant amounts of EtO may be formed internally, independent of external exposure.
This paradigm shift in understanding EtO formation raises compelling questions about how to disentangle the relative contributions of environmental versus endogenous sources. Prior models of carcinogenic risk primarily focused on inhaled EtO, but with endogenous formation emerging as a relevant pathway, dose-response assessments and biomarker interpretations need reevaluation. The current study spearheaded by Lin, Thayer, White, and colleagues dives deep into this complex biochemical interplay, employing advanced biomarkers and exposure metrics to quantify the human internal burden of ethylene oxide resulting from ethylene exposure.
The investigative team utilized a combination of in vivo human studies and ex vivo assays to trace the biotransformation routes of ethylene into ethylene oxide. By integrating sensitive analytical techniques such as mass spectrometry-based detection of EtO-DNA adducts, which are hallmark indicators of ethylene oxide’s genotoxic interaction with cellular DNA, the researchers provided compelling quantitative evidence. Their data demonstrate that exposure to ethylene, whether from exogenous sources or generated endogenously via oxidative stress, correlates with measurable increases in ethylene oxide formation within human tissues.
Significantly, these findings open new avenues for understanding the baseline risks the general population faces from involuntary ethylene oxide exposure. Unlike traditional toxicants delivered solely through the environment, ethylene oxide’s dual origin implies that background levels detected in non-occupationally exposed individuals may partly stem from their own metabolism. This complicates the identification of exposure “thresholds” and necessitates consideration of individual physiological status, including oxidative stress levels and metabolic rates, when forecasting cancer risk linked to EtO.
Moreover, the study elucidates the critical role lipid peroxidation plays in initiating internal ethylene synthesis, which in turn oxidizes to reactive ethylene oxide. Given oxidative stress’s central involvement, this implies a synergistic interaction between lifestyle, environmental factors, and inherent metabolic processes in influencing carcinogenic EtO loads. Conditions known to elevate lipid peroxidation, such as chronic inflammation and certain dietary habits, could amplify endogenous EtO formation, thereby modifying individual susceptibility to genotoxic insult and malignancy.
From a regulatory perspective, these insights challenge conventional exposure guidelines and occupational safety limits established solely based on external ethylene oxide monitoring. Risk assessors may need to incorporate endogenous production variables into their models to more accurately assess population risks. This shift emphasizes the importance of personalized exposure science, taking into account internal biochemical markers alongside environmental measurements to holistically address carcinogen exposure and its consequences.
Further implications of this research touch on smoking cessation and urban air quality management policies. Given that smoking contributes both ethylene and ethylene oxide through combustion byproducts, efforts to reduce tobacco use could have a dual impact on lowering exogenous EtO levels and possibly modulating endogenous processes related to lipid peroxidation. Similarly, improving air quality by limiting ethylene emissions from industrial and vehicular sources may reduce the overall ethylene burden in the environment, thereby decreasing internal EtO formation triggered by inhaled ethylene.
The methodological advances underpinning this study set a new standard for environmental exposure science. By combining precise chemical analysis with biochemical markers of DNA damage, the research team has opened a pathway for future studies to unravel other endogenous-exogenous toxicant dynamics. This integrative approach promises to transform how toxicologists and epidemiologists interpret biomonitoring data, drug metabolism, and environmental carcinogenesis.
Looking ahead, this research urges a reevaluation of how we perceive internal chemical exposures and their health risks. Traditional toxicology often treats internal generation of harmful metabolites as secondary or negligible compared to external sources. The new evidence suggests that for ethylene oxide, endogenous pathways represent a crucial source that could significantly influence lifetime cancer risk assessments, especially in vulnerable populations with heightened oxidative stress and metabolic sensitivities.
At the intersection of environmental science, molecular toxicology, and public health, uncovering the endogenous formation of ethylene oxide via ethylene oxidation demands a nuanced dialogue between researchers, policymakers, and the public. Communicating these developments is essential to appropriately frame exposure risks and foster support for integrated strategies aimed at mitigating carcinogenic burdens from both environmental and metabolic origins.
In conclusion, the breakthrough findings by Lin et al. illuminate the hidden biochemical pathways contributing to ethylene oxide carcinogen exposure in humans. Ethylene’s dual role as an environmental pollutant and endogenous metabolite highlights the complex nature of toxicant exposure, challenging traditional boundaries between external and internal sources. As scientific understanding evolves, so too must our approaches to monitoring, regulating, and ultimately reducing cancer risks associated with ethylene oxide. This study sets a transformative precedent, heralding a new frontier in exposure science where molecular insights drive improved public health outcomes.
Subject of Research: The relationship between ethylene exposure and endogenous ethylene oxide levels in humans.
Article Title: Uncovering the connection: ethylene exposure and endogenous ethylene oxide levels in humans.
Article References:
Lin, YS., Thayer, K.A., White, P. et al. Uncovering the connection: ethylene exposure and endogenous ethylene oxide levels in humans.
J Expo Sci Environ Epidemiol (2025). https://doi.org/10.1038/s41370-025-00826-7
Image Credits: AI Generated
DOI: 20 November 2025
Tags: air pollution and cancercarcinogenic effects of EtOendogenous pathways of ethylene oxideenvironmental health researchethylene exposureethylene oxide formationhuman health risksindustrial emissions and air qualityoccupational exposure to carcinogenspublic health policies on chemical riskstobacco smoke and healthtoxicological science advancements
