Chemicals: Cocktail Effects

The European Commission has announced a “new process” aimed at getting to grips with “cocktail effects" (also known as combination effects) of chemicals in the daily environment. This refers to the fact that some chemicals which may be relatively harmless in themselves can become quite harmful in combination with each other.

This could lead to a new dimension in future legislation. In presenting a report on this issue published this past week, the Commission said it will “identify ‘priority mixtures’ to be assessed and ensure that the different strands of EU legislation deliver consistent risk assessments for such priority mixtures.”

Background

Citizens are exposed to chemical substance mixtures every day. Current EU law sets strict limits for the amounts of particular chemicals allowed in food, water, air and manufactured products. The potentially toxic effect of chemicals in combination however has not been adequately examined.

This was recognised in a 2009 call from Member States for the Commission to report on the "combination" or "cocktail" effect of chemicals. That same year, the results of a Danish study indicated that it was necessary to reduce the exposure of young children to chemical mixtures found in food, indoor air and consumer products.

This Communication is the result of the Member State’s call. It sets out a programme aimed at assessing how the toxicity of chemicals mixtures can be better addressed under EU law. The Communication is based on a joint opinion of three Scientific Committees and a study on mixture toxicity financed by the Commission.

Chemical Mixtures and EU law

The Communication provides some context on current EU chemical legislation, which is mostly founded on assessments on the individual negative effects of chemical substances. There is also however a body of EU legislation that deals with chemical mixtures.

Mixtures can be produced voluntarily or can happen accidentally:
• Intentional mixtures can be easily assessed and regulated since their composition is well known. EU chemical legislation covers this kind of mixtures, good examples are the rules on composition of cosmetics or rules on classification labelling and packaging of mixtures.
• Non-voluntary mixtures can originate from single or multiple sources. When the mixture is discharged or emitted into the environment from a single source, difficulties in assessing the mixture depend on the knowledge of its composition. There are very few examples of EU legislation that specifically require the assessment of these kinds of mixtures.

Focus on multiple-source mixtures

The Communication focuses on mixtures originating from multiple sources, as there are only a limited number of EU measures currently regulating these mixtures. This, says the Commission, is especially true in the fields of pesticide residues and workplace risks.

According to the Commission, EU chemical legislation has no mechanism for a systematic and integrated assessment of mixture effects that take into account different sources, routes of exposure or product types.

Small concentrations of different substances

Chemicals which are present in a mixture can act jointly or independently, depending on whether they have the same mode of action or not. The Scientific Committees indicated that, even in small concentrations, chemicals with common modes of action can act jointly in a way that increases the overall toxicity. On the other hand, there is no evidence available to indicate that mixtures composed of chemicals acting independently can influence overall toxicity.

As regards ecological effects however, the Scientific Committees concluded that the interaction of chemicals with a dissimilar mode of acting is uncertain. Exposure to mixtures composed of chemicals acting independently could therefore be a concern.

Identifying priorities

Since the number of possible mixtures to which persons and the environment are exposed is so large, the Commission believes it is necessary to establish a filter that allows focusing on the most relevant mixtures.

The Scientific Committees therefore proposed criteria that will allow mixtures of potential concern to be prioritised. The criteria are as follows: 
• The potential serious negative effects of the chemicals.
• Human or environmental exposure at significant levels.
• The scale of exposure.
• The persistence of chemicals in the body or environment.

Scientific assessment

Once a mixture has been identified as relevant, it has to be tested in order to assess its toxicity. According to the Scientific Committees, there are different methods currently available for assessing the toxicity. However, the application of one or other method will depend on the mode of action of the chemical substances in the mixture:
• In cases where chemicals act in a similar mode, a “dose addition” approach would be appropriate. 
• When the chemicals act in a dissimilar mode, an “independent action” approach should be applied.
• If there is not enough information about the mode of action of the chemicals, a “dose addition” approach may result in an over-prediction of toxicity, but this is still preferable since the “independent action” approach may underestimate toxicity.

Knowledge and Data gaps

The Scientific Committees have identified problems in the application of certain methodologies available, which make them less potentially effective. The Commission also highlights in the Communication that there are important data and knowledge gaps impeding a more systematic and effective application of the methodologies. For example:
• There is a lack of knowledge on the different factors (location, frequency, etc.) that explain the exposure of persons and the environment to certain chemical mixtures.
• There is not enough information on the mode of action of many chemicals.
• Interactions of chemicals in mixtures are difficult to foresee.

Evaluation of the current situation

The Scientific Committees also considered that, in many cases, these knowledge and data gaps undermine a robust scientific analysis. A toxicology assessment of chemical mixtures requires a good knowledge of: 
• The components of a mixture. 
• Their mode of action. At the moment all this information is rarely available and can be very expensive. In the field of ecotoxicology (with regard to the environment), the availability of information is even more limited.
The Commission concludes that, regardless of the data and knowledge gaps, it is possible to assess mixture toxicity in a more systematic way. In the most complicated cases, when there is not enough information on the chemicals’ mode of action, the “dose addition” approach can be applied since it will always provide a higher level of protection because of the overestimation of negative effects. Nevertheless, the data and knowledge gaps and the high level costs must be taken into account.

Action plan

After taking all these points into account, the Communication outlines a series of actions that the Commission will take in order to achieve a more comprehensive and integrated assessment of the cumulative effects of different chemicals. These include:
• Creating an ad hoc working group to ensure a consistent assessment of priority mixtures and to coordinate the work of the relevant agencies and authorities.
• Developing technical guidelines to promote a consistent approach to the assessment of priority mixtures across different pieces of EU legislation by June 2014. These guidelines would not replace existing rules or impose additional obligations or burdens on economy operators.
• Improving the understanding of the chemical mixtures to which persons and the environment are exposed, by reviewing data which is already collected under EU legislation or EU funded research projects, and creating a platform for chemical monitoring data in order to promote a coherent approach on the generation, collection, storage and use of chemical monitoring data.
• Supporting, through Horizon 2020 (the future EU fund programme for research and innovation), projects or researches on (i) the mode of action of chemicals, (ii) the grouping of chemicals into categories or assessment groups, (iii) the prediction of interactions, and (iv) the identification of chemical substances that are the main drivers of mixture toxicity.
• Drawing up a report in 2015 to take stock of the progress achieved.