New strategies for chemical risk assessment in occupational medicine

I. lavicoli, L. Fontana, V. Leso | Dipartimento di Sanità Pubblica, Sezione di Medicina del Lavoro, Università degli Studi di Napoli "Federico II", Napoli, Italy

Introduction. The European Green Deal, the European Union's new growth strategy, has set the goal of achieving a sustainable, climate-neutral, and circular economy by 2050 by promoting better health and environmental protection through the elimination of pollution and the creation of an environment free of toxic substances [1]. This strategy involves: phasing out the most harmful chemicals used for non-essential purposes; minimizing and, where possible, replacing those that may have adverse effects on human health and the environment; ensuring safer and more sustainable use of all chemicals from the design stage onwards [1]. This approach has significantly influenced the exposure scenario to chemicals of the general population and workers, both quantitatively, with a general reduction in exposure levels (to which the implementation of prevention and protection measures in the workplace has also contributed), and qualitatively, with the introduction of innovative chemicals, materials, and processes. These changes, together with a health protection perspective that recognizes the interconnection between people, animals, and ecosystems in a “One Health” vision [2], inevitably require innovative strategies for chemical risk assessment and management (CRM).
Objectives. An innovative approach to CR assessment requires advanced, sensitive, and specific models and tools for current and future exposures that are constantly decreasing, allowing for the assessment of the hazardous properties of substances, materials, and processes; aspects concerning occupational safety and health in production processes; elements relating to human and environmental health in the application phases; as well as environmental, economic, and social sustainability [3,4]. Therefore, the objective of the study was to analyze the most innovative RC assessment strategies and identify the contributions/benefits that Occupational Medicine (OM) can offer/receive from their application.
Methods. An analysis was carried out of the scientific literature available on the PubMed, Scopus, and ISI Web of Science search engines and of the gray literature, including documents produced by international research bodies and European Commission communications, in order to extract information useful for achieving a comprehensive overview of the definition, design, implementation, and practical application of new strategies and innovative models for RC assessment. The search string used included the following keywords: “next-generation risk assessment,” “new approach methods,” “pharmacokinetic modeling,” “safety by design,” “safety and sustainability by design,” “structure-activity relationship,” “quantitative structure-activity relationship,” to narrow the field of application to topics of interest, and “chemical risk assessment,” “chemical risk management” to define the context of RC assessment and management. A critical analysis of the documentation found was carried out in order to describe the methodologies and models proposed, the possible critical issues in their application, the opportunities offered to the occupational health and safety management system, and the future prospects for research in this field.
Results. Next Generation Risk Assessment (NGRA), an innovative approach to RC assessment, follows a hypothesis-driven, exposure-based tiered scheme aimed at characterizing
RC while avoiding animal testing [5]. NGRA is based on new approach methodologies (NAM) that include in vitro, ex vivo, in chemico, in silico, read-across, and omics-based analyses, as well as their possible combinations, generally applied in the hazard identification phase. Modeling applied to the study of the kinetics of substances under physiological conditions (Physiologically Based Kinetic modeling - PBK) allows quantitative data on internal dose and effective dose to be obtained [6]. The integration of more traditional biological monitoring data into PBK models allows environmental exposure levels to be indirectly reconstructed, improving understanding of the relationship between exposure, internal dose, and possible adverse effects. Structure-activity relationship (SAR) models, including quantitative models (QSAR), predict the physicochemical, biological, and environmental properties of chemicals based on their structure. The data obtained from all these models must be findable, accessible, interoperable, and reusable (FAIR) according to an “open science” model that maximizes the application impact of research. The use of these innovative approaches will make it possible to obtain substances, materials, and processes that are “safe and sustainable by design,” with particular consideration for the safety and health of exposed workers. This latter strategy avoids the production of substances that may be hazardous to human health and the environment, while ensuring their functionality, and ensures their sustainability throughout their life cycle, reducing their impact on the environment, climate change, the use of raw materials, ecosystems, and biodiversity [1].
Conclusions. New and promising strategies for RC assessment are currently available. However, some critical issues related to the validation of methods, the interpretation of the data obtained, and the standardization of procedures will need to be overcome to ensure their wider application. Given its experience in RC assessment and management and the availability of environmental, biological, and clinical monitoring data, the MdL represents a natural link between biotechnological-mathematical-computational sciences and the protection of the health and safety of workers and the general population. The workplace is, in fact, an ideal context for studying and testing the effectiveness of such models, particularly with regard to their possible role in a dynamic and predictive assessment of CR, in relation to the different stages of production and non-standard working conditions (maintenance work, accidents). The MdL, which has always taken a preventive and proactive approach to the issue of health in relation to occupational risks, will be able to ensure the application of the NGRA in a ‘One Health’ vision, taking into account individual susceptibility conditions that require a ‘precision’ approach and guiding the adoption of appropriate prevention and protection measures for RC management that guarantee safety, health, and sustainability.