Towards a systematic use of effect biomarkers in population and occupational biomonitoring
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Materia
Exposure science Mixture assessment Adverse outcome pathway (AOP) Physiologically based pharmacokinetic (PBPK) Biomonitoring Risk assessment
Fecha
2020Referencia bibliográfica
Jeddi, M. Z., Hopf, N. B., Viegas, S., Price, A. B., Paini, A., van Thriel, C., ... & Pasanen-Kase, R. (2021). Towards a systematic use of effect biomarkers in population and occupational biomonitoring. Environment International, 146. [doi: 10.1016/j.envint.2020.106257]
Resumen
Effect biomarkers can be used to elucidate relationships between exposure to environmental chemicals and their
mixtures with associated health outcomes, but they are often underused, as underlying biological mechanisms
are not understood. We aim to provide an overview of available effect biomarkers for monitoring chemical
exposures in the general and occupational populations, and highlight their potential in monitoring humans
exposed to chemical mixtures. We also discuss the role of the adverse outcome pathway (AOP) framework and
physiologically based kinetic and dynamic (PBK/D) modelling to strengthen the understanding of the biological
mechanism of effect biomarkers, and in particular for use in regulatory risk assessments. An interdisciplinary
network of experts from the European chapter of the International Society for Exposure Science (ISES Europe)
and the Organization for Economic Co-operation and Development (OECD) Occupational Biomonitoring activity
of Working Parties of Hazard and Exposure Assessment group worked together to map the conventional
framework of biomarkers and provided recommendations for their systematic use. We summarized the key aspects of this work here, and discussed these in three parts. Part I, we inventory available effect biomarkers and
promising new biomarkers for the general population based on the H2020 Human Biomonitoring for Europe
(HBM4EU) initiative. Part II, we provide an overview AOP and PBK/D modelling use that improved the selection
and interpretation of effect biomarkers. Part III, we describe the collected expertise from the OECD Occupational
Biomonitoring subtask effect biomarkers in prioritizing relevant mode of actions (MoAs) and suitable effect
biomarkers. Furthermore, we propose a tiered risk assessment approach for occupational biomonitoring.
Several effect biomarkers, especially for use in occupational settings, are validated. They offer a direct
assessment of the overall health risks associated with exposure to chemicals, chemical mixtures and their
transformation products. Promising novel effect biomarkers are emerging for biomonitoring of the general
population. Efforts are being dedicated to prioritizing molecular and biochemical effect biomarkers that can
provide a causal link in exposure-health outcome associations. This mechanistic approach has great potential in
improving human health risk assessment. New techniques such as in silico methods (e.g. QSAR, PBK/D modelling) as well as ‘omics data will aid this process.
Our multidisciplinary review represents a starting point for enhancing the identification of effect biomarkers
and their mechanistic pathways following the AOP framework. This may help in prioritizing the effect biomarker
implementation as well as defining threshold limits for chemical mixtures in a more structured way. Several ex
vivo biomarkers have been proposed to evaluate combined effects including genotoxicity and xeno-estrogenicity.
There is a regulatory need to derive effect-based trigger values using the increasing mechanistic knowledge
coming from the AOP framework to address adverse health effects due to exposure to chemical mixtures. Such a
mechanistic strategy would reduce the fragmentation observed in different regulations. It could also stimulate a
harmonized use of effect biomarkers in a more comparable way, in particular for risk assessments to chemical
mixtures.