Assessing “chemical mixtures” – current approaches and future priorities

People, animals and the environment can be exposed to multiple chemicals at once from a variety of sources, but current risk assessment is usually carried out on one chemical substance at a time. EFSA has prioritised addressing the assessment of combined exposure to multiple chemicals because of the challenges this poses for the Authority’s scientific work. EFSA has already developed some approaches in this field: recent examples include the risk assessment of mixtures of pesticides for humans and for bees, and mixtures of contaminants for humans. Today’s publication of an EFSA review of international frameworks for assessing chemical mixtures will support the roll-out of harmonised terminology and methodologies for risk assessors. The report also provides a platform for future EFSA work in this area.

EFSA considered frameworks from four national authorities (Norway, UK, two from the United States), two international organisations (World Health Organization–WHO, European Commission), as well as the Authority’s own work in this field. Among the key findings and next steps of EFSA’s review are:

  • To identify chemical mixtures of priority for risk assessment EFSA recommends using criteria for a risk based approach that take into account both the toxicity of the chemicals concerned as well as exposure or anticipated exposure to these chemicals.
  • There are limited data on the toxicity of groups or similar groups of chemical substances. When such data do not exist, evidence that different substances cause similar adverse effects on organs and/or physiological systems is compiled to create so-called assessment groups, which are used to predict the possible combined toxic effects of the chemicals in the group. Substances in the mixture may work by a similar ‘mechanism of toxicity’ (that is, the major steps leading to an adverse effect) and the doses can simply be added to predict the effects (dose addition); or they may interact together to become more toxic (synergism) or less toxic (antagonism).
  • More information is needed to understand how chemicals are eliminated from the body, how they interact within the body and what are their potential effects in humans and/or animals. EFSA is promoting research and data collection efforts in this area: the Authority recently launched a call for tender related to the toxicity of multiple chemicals in bees and has started a systematic review of the effects of chemical mixtures (including pesticides, contaminants and other chemicals present in the food chain) for human risk assessment.
  • New tools such as mathematical and biological models are being used to predict both the bodily processes for breaking down and eliminating chemicals as well as mechanisms of toxicity. EFSA will continue to provide scientific support for the development of such tools in particular for priority groups of chemicals.
  • Harmonised terminology is needed to support these developments and EFSA recommends that risk assessors follow the lead shown by WHO’s International Programme on Chemical Safety in the useof standardised language.

The full report and the recent call:

In related work, an EFSA opinion also published today sets out a general methodology for risk assessment of multiple pesticides:

Notes to editors
  • “Chemical mixtures” refer to combined exposure to multiple chemicals. Food may contain many different chemicals naturally such as nutrients and plant toxins produced by weeds, or man-made chemicals such as pesticides and environmental contaminants like dioxins. The number of combinations of chemicals is potentially vast and they can come from a variety of sources: food, medicines or consumer goods like cosmetics. These chemicals may raise health concerns depending on their toxicity and the level of exposure in food or the environment.
  • How do scientists assess risks of exposure to chemical mixtures? For a single chemical scientists review all the toxicity data to set a safe level of use, where this is possible, and compare it with consumer exposure (for example through food). Scientists can then predict potential health risks. For multiple chemicals, scientists have developed methods which use the same principles but with some differences. 
    • Firstly, scientists define whether a risk assessment for a group of chemicals is needed depending on consumer exposure or on the chemicals’ toxicity. Who is exposed (general population, children, pregnant women, elderly, etc. ) and by how much? Is the exposure one-off or is it spread over time? This step is called the problem formulation.
    • The next step is to assess the toxicity of the group of chemicals and identify how these substances are metabolised in the body and how they may express their toxicity, often referred to as “mode of action”. Scientists analyse the information available on the toxicity using scientific criteria in a so-called “weight of evidence approach”. Then, if relevant information is available, they make one of three assumptions about the toxicity – dose addition, response addition and interaction – to determine the potential health risks.
    • Dose addition means that the chemicals have a similar toxicity and after determining their individual potency, the doses are added up for the risk assessment.
    • For response addition scientists consider the independent toxic effects of each substance in the mixture and include these together when carrying out the risk assessment.
    • Interactions are more complex. Chemicals can become more toxic when combined, which is called “synergism”. On the other hand, they can be less toxic when combined, which is known as “antagonism”. The mechanisms behind synergism and antagonism are complex. Two important ones are: an increase or decrease in the body’s ability to detoxify and eliminate the compounds, and an increase or decrease in toxicity of the chemical(s). If there is evidence of such interactions, scientists collect the information to take these effects into account in the risk assessment.
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