Use of Effect Biomarkers for Regulatory Risk Assessment of Chemical Mixtures

Abstract

General and workers populations are exposed to a wide range of chemicals in their daily lives. Exposures to these chemical mixtures depend on the different environments, routes of exposures (inhalation, skin, and ingestion), and sources. Human Biomonitoring (HBM) is a powerful tool for assessing the uptake of chemicals into the human body in a holistic manner. In this context, effect biomarkers have become an essential part of biomonitoring programs because they reveal adverse effects from chemical exposures also accounting for unknown mixtures effects, the most common human exposure scenario. Effect biomarkers enable us to link chemical exposures to their combined health effects and disease development. This effect biomarker approach implies a needed paradigm shift in regulatory risk assessment from investigating one chemical substance at the time to exposures to chemical mixtures. To date, several relevant effect biomarkers have been validated and some effect biomarkers have been implemented as part of Adverse Outcome Pathway (AOP). The previous multidisciplinary review performed represents a basis for enhancing the identification of relevant effect biomarkers and their mechanistic pathways following the AOP framework. This approach offers a systematic understanding and enables us to bring the use of effect biomarkers and chemical mixture risk assessment into regulatory use by defining mixture thresholds. Guiding principles and examples for defining AOP related effect thresholds for relevant Mode of Actions (MoAs) will be elaborated in an OECD follow up activity with the expert’s engagement from more than 25 institutes and organizations.