On 10 and 11 December 2013 an international conference was held in Paris on the research and risk assessment challenges posed by chemical mixtures. The goal of these two days, organised by the French health agency, ANSES, and the German and Danish institutes, the BfR and DTU, was to stimulate the exchange of scientific knowledge and practices on this topic. All the participants were in agreement as to the necessity to pursue joint interdisciplinary research projects, in Europe and on an international level.
Close to 400 people attended the conference, during which researchers and scientists from ten European and trans-Atlantic countries presented and discussed the results of their studies, emphasising significant progress in research on exposures to chemical mixtures and their effects. The studies presented at the conference involve the development of new methods, models, databases and biomarkers to identify and assess the hazards, exposures and risks to health posed by chemical mixtures. However, the issues raised during the various sessions and the concluding round table discussion brought to light certain gaps which need to be filled.
Real progress but more work needed
Humans are exposed to a large number of substances, alone or in mixtures, in food, water, air and consumer products. A high level of exposure to mixtures has been observed, especially in occupational environments and in situations where they may be associated with other risk factors. Several presentations given during the conference showed progress in the level of knowledge with regard to potential mixture effects and exposure to e.g. pesticides (fungicides, etc.). However, over the last few years research has concentrated mainly on pesticides, with less of its efforts being spent on other classes of chemical mixtures. Due to the many concerns expressed, in particular during the round table event, research efforts need to be extended to other classes of chemical substances. In addition, the existing methods used for assessment within the European regulatory framework need to evolve in order to better account for the combined effects of chemical mixtures.
Tools needed to improve knowledge and assess risks
Numerous methods exist for characterising exposures, improving scientific knowledge of their effects and assessing the risks to human health associated with chemical mixtures. Among these, an interdisciplinary approach is of paramount importance for effectively integrating and interpreting data, by working along with toxicologists, biomathematicians, epidemiologists, clinicians, toxicokinetics specialists, social scientists, etc.
The use of data from in vitro studies is necessary in order to better understand the modes of action linked to adverse effects. These studies must also take into account realistic concentrations in order to obtain robust results. Nevertheless, no in vitro method can suffice on its own to assess the effects of chemical mixtures. Therefore, in order to gain a better understanding of the potential adverse effects of chemical mixtures, in vivo studies remain essential. However, if noteworthy progress is to be made, research work must also take the various routes of exposure into account. Support for wide-scale European studies is also clearly needed, that combine biomonitoring data with well-documented sources, data on the levels of exposure to the various chemical compounds to which people are exposed, and health status data.
The "substance by substance" approach is no longer enough to assess combined effects
The "substance by substance" approach to risk assessment is questionable and has been deemed insufficient for assessing the combined effects of substances. According to some of the presentations, for endocrine disruptors in particular but also for multiple pesticide residues, this approach might not – and for others it cannot – provide enough protection from possible chemical mixture effects. Therefore, whilst further research to enhance the empirical basis for prediction of mixture toxicity is indispensable, improvements in current risk evaluation practices are also needed.
The feasibility of using in vivo studies for the cumulative risk assessment of endocrine disruptors was discussed during the conference, and it was suggested that a default approach to risk assessment based on dose addition be applied.
Furthermore, when assessing the cumulative risks of mixtures (endocrine disruptors, for example), taking only molecular mechanisms of action (in vitro data, bioinformatics, etc.) as a starting point appears insufficient. The criteria for grouping together substances should be clear and simple, taking into account the different types of adverse health outcomes (fertility, neurotoxicity, metabolic, etc.) as well as the likelihood of co-exposures.
International research collaborations to be pursued
The issue of chemical mixtures and their effects is a major scientific challenge that ANSES, the BfR and DTU have decided to tackle in the framework of their cooperation agreement. This joint conference has enabled scientists to agree upon the need to pursue research work on these topics and to develop collaboration initiatives on the European and international levels, especially with regard to methods for risk assessment and expert appraisal.