Biological monitoring of occupational exposures: prospects and limitations of epigenetic biomarkers

V. Bollati,^1,2 L. Ferrari,^1,2 M. Carugno,^1,2 M. Bonzini,^1,2 S. Fustinoni,^1,2 E.M. Biganzoli,^3,4 A.C. Pesatori^1,2  | ¹Lab. EPIGET-Dipartimento di Scienze Cliniche e di Comunità,  Università degli Studi di Milano; ²Fondazione IRCCS Ca' Granda, Policlinico di Milano; ³Dipartimento di Scienze Biomediche e Cliniche (DIBIC), Università degli Studi di Milano; ⁴Unità di Ricerca Clinica e Statistica Medica, Ospedale "L. Sacco", Milano, Italy

Introduction. Biological monitoring of occupational exposures is a crucial aspect of occupational medicine, allowing the assessment of the absorption and effect of toxic agents/risk factors on workers.
In this context, epigenetic biomarkers, such as DNA methylation, histone modifications, and non-coding RNAs, change in response to exposure to environmental and occupational factors, both acutely and cumulatively, and influence susceptibility to disease.
It is essential to consider different exposures such as those to chemical and physical agents, but also less conventional ones. Among these, physical activity can have chronic or acute damaging effects if not managed correctly, but in the same way it can also be an essential compensatory factor of benefit, especially for sedentary jobs but more generally in promoting human well-being and health.
The potential and limitations of epigenetic biomarkers in monitoring occupational exposures and possible risk compensation factors associated with favorable lifestyles are explored, discussing the practical applications and challenges still to be overcome for the integration of these biomarkers into occupational health and safety promotion practices in relation to mechanisms of adaptation to the professional and human environment in general.
Objectives. The main objective is to explore and evaluate the use of epigenetic biomarkers in monitoring occupational exposures, including the effects of less traditional exposures such as physical activity. In particular, the presentation aims to use prototypical examples of epidemiological studies and, in this context: - Analyze the most recent studies demonstrating the effectiveness of epigenetic biomarkers in detecting and quantifying occupational exposures. - Identify how epigenetic biomarkers can offer an integrated view of biological responses to occupational exposures compared to traditional biomarkers.
- Explore the role of epigenetic biomarkers in providing early indications of susceptibility to occupational diseases.
Methods. The use of epigenetic biomarkers in monitoring occupational exposures will be described and explored through the analysis of four paradigmatic examples.
Investigation of the exposure of gas station attendants, traffic police, and office workers to benzene (1).
Characterization of an extended panel of epigenetic biomarkers in a population of steel mill workers (2-4).
Assessment of a population of nurses with current or past exposure to night shifts (5).
Epigenetic characterization of subjects in the HEBE intervention study, aimed at improving the well-being of workers at the University of Milan through a protocol of regular physical activity and a balanced diet (6).
Results. Critical discussion of the studies highlighted both potential advantages and limitations of the use of epigenetic biomarkers in monitoring occupational exposures and the effects of such exposures. Epigenetic biomarkers may be effective in detecting early biological changes in response to various occupational exposures. These changes, which may include both harmful effects and positive adaptive phenomena, provide timely indications of biological effects before clinical symptoms manifest.
Epigenetic changes observed in response to exposures can also serve as prognostic and response markers, predicting the future risk of developing occupational diseases and the effectiveness of prevention interventions. This is particularly important in work settings where health and safety promotion are essential for damage prevention, along with early interventions to significantly reduce the incidence of chronic diseases related to occupational exposure. Unlike traditional biomarkers, epigenetic biomarkers offer a dynamic view of biological changes over time, reflecting not only current exposure but also past exposures and their interaction with environmental and behavioral factors. This feature makes them powerful tools for continuous monitoring of workers' health, as they can capture the cumulative effect of exposures. Because of this characteristic, epigenetic biomarkers cannot serve as effective dose markers because they cannot directly quantify the amount of exposure to a specific agent, making it difficult to establish a precise dose-response relationship. Their sensitivity to environmental and behavioral variations makes them less suitable for measuring specific exposure to a single substance, but very useful for understanding the overall impact of a work environment on health. - Identify how epigenetic biomarkers can offer an integrated view of biological responses to occupational exposures compared to traditional biomarkers.
- Explore the role of epigenetic biomarkers in providing early indications of susceptibility to occupational diseases.
Methods. The use of epigenetic biomarkers in monitoring occupational exposures will be described and explored through the analysis of four paradigmatic examples.
Investigation of benzene exposure among gas station attendants, traffic police, and office workers (1).
Characterization of an extended panel of epigenetic biomarkers in a population of steel mill workers (2-4).
Assessment of a population of nurses with current or past exposure to night shifts (5).
Epigenetic characterization of subjects in the HEBE intervention study, aimed at improving the well-being of workers at the University of Milan through a protocol of regular physical activity and a balanced diet (6).
Results. Critical discussion of the studies highlighted both potential advantages and limitations of the use of epigenetic biomarkers in monitoring occupational exposures and the effects of such exposures. Epigenetic biomarkers may be effective in detecting early biological changes in response to various occupational exposures. These changes, which may include both harmful effects and positive adaptive phenomena, provide timely indications of biological effects before clinical symptoms manifest.
Epigenetic changes observed in response to exposures can also serve as prognostic and response markers, predicting the future risk of developing occupational diseases and the effectiveness of prevention interventions. This is particularly important in work settings where health and safety promotion are essential for damage prevention, along with early interventions to significantly reduce the incidence of chronic diseases related to occupational exposure. Unlike traditional biomarkers, epigenetic biomarkers offer a dynamic view of biological changes over time, reflecting not only current exposure but also past exposures and their interaction with environmental and behavioral factors. This feature makes them powerful tools for continuous monitoring of workers' health, as they can capture the cumulative effect of exposures. Because of this characteristic, epigenetic biomarkers cannot serve as effective dose markers because they cannot directly quantify the amount of exposure to a specific agent, making it difficult to establish a precise dose-response relationship. Their sensitivity to environmental and behavioral variations makes them less suitable for measuring specific exposure to a single substance, but very useful for understanding the overall impact of a work environment on health. Although epigenetic biomarkers have the potential to be used as risk markers, further research is needed to validate this application in the occupational field. Individual variability in epigenetic response and the complexity of gene-environment interactions require in-depth studies to identify epigenetic patterns that can accurately predict the risk of occupational diseases along with the beneficial effects of interventions. Furthermore, the interpretation of epigenetic data requires sophisticated analysis integrated with other forms of biological and environmental data, indicating challenges of increasing complexity in the use of massive exposome information with computational biostatistical methods based on algorithmic inference.
Finally, the use of epigenetic biomarkers requires the standardization of sampling and analysis techniques. Currently, variability in methodologies can affect the comparability of data and the applicability of these markers in clinical settings. It is essential to develop standardized and validated protocols for the collection, storage, and analysis of biological samples to ensure that results are reliable and reproducible. Only through rigorous standardization and validation will it be possible to effectively integrate epigenetic biomarkers into clinical and occupational monitoring practices, improving the prevention and management of work-related diseases.
Conclusion. Epigenetic biomarkers offer new opportunities to improve occupational exposure monitoring, thanks to their ability to detect early effects and provide prognostic information. However, their practical application is limited by certain technical and interpretative challenges. Further research and methodological developments are needed to fully exploit the potential of these biomarkers, ensuring that they can be used effectively in protecting workers' health.