Overview on legislation and scientific approaches for risk assessment of combined exposure to multiple chemicals: the potential EuroMix contribution

Abstract

This article reviews the current legislative requirements for risk assessment of combined exposure to multiple chemicals via multiple exposure routes, focusing on human health and particularly on food-related chemicals. The aim is to identify regulatory needs and current approaches for this type of risk assessment as well as challenges of the implementation of appropriate and harmonized guidance at international level. It provides an overview of the current legal requirements in the European Union (EU), the United States and Canada. Substantial differences were identified in the legal requirements for risk assessment of combined exposure to multiple chemicals and its implementation between EU and non-EU countries and across several regulatory sectors. Frameworks currently proposed and in use for assessing risks from combined exposure to multiple chemicals via multiple routes and different durations of exposure are summarized. In order to avoid significant discrepancies between regulatory sectors or countries, the approach for assessing risks of combined exposure should be based on similar principles for all types of chemicals. OECD and EFSA identified the development of harmonized methodologies for combined exposure to multiple chemicals as a key priority area. The Horizon 2020 project “EuroMix” aims to contribute to the further development of internationally harmonized approaches for such risk assessments by the development of an integrated test strategy using in vitro and in silico tests verified for chemical mixtures based on more appropriate data on potential combined effects. These approaches and testing strategies should be integrated in a scientifically based weight of evidence approach to account for complexity and uncertainty, to improve risk assessment.

Keywords:

• Cumulative risk assessment
• chemical mixtures
• pesticides
• combined exposure
• dietary exposure
• harmonization
• testing strategies
• policy making

Acknowledgments

The research leading to these results received funding from the European Union’s Horizon 2020 research and innovation program [grant agreement 633172 (Euromix)].

Declaration of interest

This research is sponsored by European Commission within the EuroMix project. We have disclosed those interests fully to the European Commission and have in place an approved plan for managing any potential conflicts arising from this arrangement. ARB was employed by Imperial College London, where he was involved in academic research and teaching in the fields of biomedicine and toxicology until he retired in June 2017. He is currently employed 4 h per week by the College to work on the EU Horizon 2020 project (EuroMix). He is or has collaborated on a number of activities on the risk assessment of combined exposures to multiple chemicals through the European Commission, FAO/WHO JECFA, FAO/WHO JMPR, WHO-IPCS, EFSA, ILSI HESI, ILSI Europe, and United Kingdom COT and COMEAP. None of these collaborative activities was remunerated and no research funding was received. He consulted for Coca-Cola and for Red Bull on the safety of certain food additives, from 2012 to 2014. This work did not involve risk assessment of combined exposure to multiple chemicals. ARB received no funding in cash or kind for his contribution to this manuscript other than funding to Imperial College London from EuroMix, as a contractual partner in the project. No further potential conflict of interest was reported by the authors.

Disclaimer

The views expressed in this article are those of the authors and do not necessarily reflect the official views, decisions or policies of the author institutions.