Towards a systematic use of effect biomarkers in population and occupational biomonitoring. (January 2021)

• Record Type: Journal Article
• Authors: Zare Jeddi, Maryam; Hopf, Nancy B.; Viegas, Susana; Price, Anna Bal; Paini, Alicia; van Thriel, Christoph; Benfenati, Emilio; Ndaw, Sophie; Bessems, Jos; Behnisch, Peter A.; Leng, Gabriele; Duca, Radu-Corneliu; Verhagen, Hans; Cubadda, Francesco; Brennan, Lorraine; Ali, Imran; David, Arthur; Mustieles, Vicente; Fernandez, Mariana F.; Louro, Henriqueta; Pasanen-Kase, Robert
• Is Part Of: Environment international. Volume 146(2021)
• Publication Date: 2021-01
• Subjects: Exposure science -- Mixture assessment -- Adverse outcome pathways (AOP) -- Physiologically based pharmacokinetic (PBPK) -- Biomonitoring -- Risk assessment; ACGIH American Conference of Governmental Industrial Hygienists -- ADME Adsorption, Distribution, Metabolism, Excretion -- AOP Adverse Outcome Pathways -- AO adverse outcome -- AOP-KB Adverse Outcome Pathway Knowledge Base -- B-Pb Blood Lead -- BBLV Binding Biological Limit Value -- Biological limit value -- BOELV Binding Occupational Exposure Limit Value -- CAD Chemical Agents Directive -- CMD Carcinogenic and Mutagenic Directive -- DNEL Derived No-Effect Level -- DNT Developmental Neurotoxicity -- EC European Commission -- ECHA European Chemicals Agency -- EFSA European Food Safety Authority -- Effect Biomarker Effect biomarkers are measurable biochemical, physiological, and behavioral effects or other alterations within an organism that depending upon the magnitude, can be recognized as associated with an established or possible health impairment or disease -- EQ Equivalent concentration, integrative response of an effect biomarker translated in an effect concentration of a reference compound -- EGMAST Extended Advisory Group on Molecular Screening and Toxicogenomics -- HBM Human Biomonitoring -- HBM4EU European Human Biomonitoring Initiative -- IOELV Indicative Occupational Exposure Limit Value -- ISES International Society for Exposure Science -- ISO International Organization for Standardization -- IUCLID International Uniform Chemical Information Database -- MIE Molecular Initiating Event -- KE Key Event -- KER Key Event Relationship -- MDA malondialdehyde -- MoA Mode of Action -- OECD Organization for Economic Co-operation and Development -- OBL Occupational Biomonitoring Level -- OBEL Occupational Biomonitoring Effect Level -- OEL Occupational Exposure Limit -- OSH Occupational Safety and Health -- PBK modelling Physiologically Based Kinetic modelling -- PBD modelling Physiologically Based Dynamic modelling -- PoD Points of Departure -- PPE Personal Protective Equipment -- RAC Risk Assessment Committee, European Chemicals Agency -- REACH Registration, Evaluation, Authorization and Restriction of Chemicals -- RMM Risk Management Measure -- SCOEL Scientific Committee on Occupational Exposure Limits -- SEGs Similar Exposure Groups -- WHO World Health Organization -- WPEA Working Party on Exposure Assessment -- WPHA Working Party on Hazard Assessment; Environmental protection -- Periodicals; Environmental health -- Periodicals; Environmental monitoring -- Periodicals; Environmental Monitoring -- Periodicals; Environnement -- Protection -- Périodiques; Hygiène du milieu -- Périodiques; Environnement -- Surveillance -- Périodiques; Environmental health; Environmental monitoring; Environmental protection; Periodicals; 333.705
• DOI: 10.1016/j.envint.2020.106257
• Languages: English
• ISSNs: 0160-4120

Abstract

Highlights: Reliable effect biomarkers are available for most of the relevant MoAs. Increasing AOP knowledge fosters the use of effect biomarkers in regulatory context. PBK/D models allow interpretation and simulation of biomarkers of effect. An inter-regulatory setting of effect-based trigger values is demanded. Effect-biomarkers have in many cases reached a level of maturity ensuring use in mixture assessments. Abstract: 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.