Data collection on toxicokinetic and toxicodynamic interactions of chemical mixtures for human risk assessment

Combined effects, Interaction, Hazard assessment, Mixture, Pharmaco/Toxicodynamics, Pharmaco/Toxicokinetics
First published in EFSA Supporting Publications
31 March 2015
External Scientific Report

The present document has been produced and adopted by the bodies identified above as author(s). This task has been carried out exclusively by the author(s) in the context of a contract between the European Food Safety Authority and the author(s), awarded following a tender procedure. The present document is published complying with the transparency principle to which the Authority is subject. It may not be considered as an output adopted by the Authority. The European Food Safety Authority reserves its rights, view and position as regards the issues addressed and the conclusions reached in the present document, without prejudice to the rights of the authors.


There is an increasing need to develop harmonised terminology, approaches and frameworks for the human risk assessment of combined exposure to multiple compounds. A number of activities have already been undertaken by EFSA, notably in the fields of pesticides and contaminants. This project aimed at providing quantitative information on combined effects of multiple compounds to support evidence-based hazard assessment. The first step was to record and collect, using extensive literature searches/systematic review methods, Pharmaco/Toxicokinetic (PK/TK) and Pharmaco-dynamic/Toxicodynamic (PD/TD) information on potential interactions between selected compounds. In vivo PD/TD and in vitro and in vivo PK/TK data were collected mostly for binary mixtures of pharmaceuticals (substrates of major routes of metabolism and known inhibitors/inducers) and major classes of regulated compounds and contaminants relevant to food safety. All data were then consolidated via meta-analyses to quantify magnitudes of interaction and their inter-individual variability for both TK and TD dimensions. Overall, this report illustrates application of systematic data collection for both human TK and TD aspects of multiple compounds to quantify magnitudes of metabolic and toxicological interactions respectively. Further analyses are recommended to integrate such magnitude of interaction and variability data in human hazard assessment of multiple compounds. © LASER Analytica, 2015

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