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Chemical mixtures

People, animals and the environment can be exposed to multiple chemicals from a variety of sources. EFSA has already developed some approaches for assessing combined exposure to multiple pesticides and contaminants in humans and multiple pesticides in bees. Our scientists are further developing new approaches and tools for harmonising how we assess risks to humans and the environment from multiple chemicals in the food chain: “chemical mixtures” and their “cocktail effects”.

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The European Commission and EFSA have published an action plan to accelerate development of the methodology for cumulative risk assessment (CRA) of pesticides, with a view to gradually implementing CRA into regulatory practice.


EFSA’s Scientific Committee developed guidance on combined exposure to multiple chemicals. This EFSA initiative is called MixTox.

EFSA is undertaking or supporting several research activities to contribute to the implementation of this guidance:

  • Data collection and analysis of combined toxicity of multiple chemicals of relevance to EFSA in the area of human, animal and environmental toxicology.
  • Development of tools for modelling (tiered approaches, population dynamics, human variability) for human and ecological risk assessment for single and multiple chemicals.



February 2021 EFSA publishes an assessment of the risks to consumers from dietary cumulative exposure to pesticide residues that have chronic effects on the nervous system (chronic erythrocyte acetylcholinesterase [AChE] inhibition). The overall conclusion is that, with varying degrees of certainty, exposure does not exceed the threshold for regulatory consideration established by risk managers.

EFSA also issues a statement comparing cumulative exposure to pesticides that have chronic effects on the thyroid system and acute effects on the nervous system for the periods 2014-2016 and 2016-2018. The results of the analysis show that consumer exposure patterns over the two periods did not change significantly and suggests that repeating cumulative risk assessments every three years can adequately address potential changes to exposure.

2020 EFSA publishes the results of its two pilot assessments on the risks posed to humans by residues of multiple pesticides in food. The assessments – one considering chronic effects on the thyroid system and the other acute effects on the nervous system – are the culmination of a multi-year collaboration between EFSA and the Dutch National Institute for Public Health and the Environment (RIVM).

The overall conclusion for both assessments is that consumer risk from dietary cumulative exposure is, with varying degrees of certainty, below the threshold that triggers regulatory action for all the population groups covered.

2019 EFSA finalises its ‘MixTox’ guidance, which equips its scientists with methodologies and tools to assess combined exposure to multiple chemicals, and related advice on how to assess the genotoxicity of substances in chemical mixtures.

2019 An EFSA research study from 2018 shows that overall in the EU awareness of chemical mixtures among the general public is quite low.

2018 EFSA publicly consults on its draft ‘MixTox’ guidance on harmonised methodologies for human health, animal health and ecological risk assessment of combined exposure to multiple chemicals.

2018 EFSA’s partners the Dutch National Institute for Public Health and the Environment (RIVM) and Wageningen University, publish data model for probabilistic cumulative dietary exposure assessments of pesticides.

2017 Launch of “OpenFoodTox” database reporting summary chemical hazards information and linking to the OECD eChemPortal. Step-by-step approaches for human and ecological risk assessment of chemical mixtures using OpenFoodTox data provide alternatives to animal testing in toxicological assessments.

2016 Public consultation on proposed MixTox scope and objectives.

2016 Joint EFSA and Dutch National Institute for Public Health and the Environment (RIVM) symposium on the future of risk assessment and toxicity testing for chemical mixtures.

2016 An RIVM-EFSA pilot study tests the Monte Carlo Risk Assessment software tool for carrying out exposure assessments of multiple pesticides.

2015 Finalisation of data collection on toxicokinetic and toxicodynamic interactions of chemical mixtures for human risk assessment and combined toxicity of multiple chemicals for animal health and ecological risk assessment.

2014 EFSA hosts scientific colloquium on harmonisation of human and ecological risk assessment of combined exposure to multiple chemicals, in Edinburgh.

2013 EFSA presents cumulative assessment group methodology for pesticides.

2013 Scientific report on international frameworks dealing with human risk assessment of combined exposure to multiple chemicals, reviewing current approaches and setting out future priorities.

2008 Evaluation of existing methodologies for identification of new approaches to assess cumulative and synergistic risks from pesticides to human health.

2006 Scientific colloquium on cumulative risk assessment of pesticides to human health.


EFSA’s Scientific Committee develops harmonised risk assessment methodologies on cross-cutting scientific matters in EFSA's areas of activities where EU-wide approaches are not already defined. The Scientific Committee considers development of guidance for harmonised methodologies for combined exposure to multiple chemicals a priority for EFSA.

EFSA reviewed available international frameworks dealing with human risk assessment of combined exposure to multiple chemicals, and consulted its expert Panels and staff on on-going activities at EFSA. The Scientific Committee recommended several follow up activities to feed into a future guidance document on this topic.

EFSA’s Panel on Plant Protection Products and their Residues is responsible for the general methodology for classifying pesticides into cumulative assessment groups. The methodology developed by the Panel uses broad criteria for inclusion of pesticides in groups to maximise consumer protection.


1. How do scientists assess chemical mixtures?

For a single chemical, scientists review available toxicity data to set a safe level for human health or the environment. They compare this with exposure (for example through food) to predict potential risks. For multiple chemicals, scientists have developed methods which use the same principles. They assess the toxicity of the group of chemicals identifying how these substances are metabolised in the body and how they might express their toxicity, often referred to as “mode of action”. Then, the toxicity information is combined with exposure information to assess potential health risks using assumptions about the combined toxicity. The most common assumptions are dose addition, response addition and interaction.

2. What is dose addition?

Dose addition means that the individual chemicals in the mixture have a similar toxicity and the doses are added up and combined with exposure for the risk assessment.

3. What is response addition?

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.

4. What is meant by interactions? What are “synergistic” and “antagonistic” effects?

Interactions are more complex. Some chemicals can become more toxic when combined. This is called “synergism”. On the other hand, other chemicals when combined 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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