External Scientific Report
External Scientific Report
External Scientific Report
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 Concentration or amount of a particular substance that is taken in by an individual, population or ecosystem in a specific frequency over a certain amount of time 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 combined exposure to multiple chemicals in the food chain: “chemical mixtures” and their effects, sometimes called “cocktail effects”.
EFSA's role
EFSA’s Scientific Committee develops harmonised risk assessment A specialised field of applied science that involves reviewing scientific data and studies in order to evaluate risks associated with certain hazards. It involves four steps: hazard identification, hazard characterisation, exposure assessment and risk characterisation methodologies on cross-cutting scientific matters in EFSA's areas of activities where EU-wide approaches are not already defined. The Scientific Committee has developed guidance to harmonise the methodologies used by EFSA's scientists for assessing combined exposure to multiple chemicals.
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. Scientists at EFSA carry out the cumulative risk assessment A method of assessing risks to health or the environment posed by multiple substances such as chemicals (CRA) of pesticides using the Panel's methodology, in line with the regulatory procedures established by EU risk managers.
A critical tool in this work is the Monte Carlo Risk Assessment (MCRA) web platform for CRA of pesticides and other chemicals. The MCRA is a central plank in EFSA’s and Member States’ efforts to assess how combined exposure to multiple chemicals can affect humans over time. The MCRA is developed by Wageningen University & Research, Biometris for the Netherlands' National Institute for Public Health and the Environment (RIVM).
EFSA undertakes and/or supports research activities to contribute to the implementation of guidance in this area:
- Data collection and analysis of combined toxicity The potential of a substance to cause harm to a living organism of multiple chemicals of relevance to EFSA in the area of human, animal and environmental toxicology.
- Development of tools for modelling (tiered approaches, population Community of humans, animals or plants from the same species dynamics, human variability Natural variations observed between members of a population, or observed over time or in different geographical locations; for example, individual variations in susceptibility to a particular toxic chemical. ) for human and ecological risk assessment for single and multiple chemicals.
Latest
Public consultation - effects on reproduction including fertility
We’re inviting scientists, national partners and those with an interest in cumulative risk assessment of pesticides to contribute to our public consultation on a draft scientific report on specific effects on the reproductive function including fertility relevant for assessment of pesticide residues.
Download the draft report and have your say!
The draft marks the first step in the assessment of possible cumulative effects on reproduction including fertility from exposure to multiple pesticides. Following the consultation our scientists, working closely with Member State partners, will consult publicly on draft cumulative assessment groups of pesticides with these types of possible health effects.
New methodology developments
Two external scientific reports test a tentative tiered approach for evaluating the acute (short-term) and chronic (long-term) effects of cumulative exposure to pesticides in the context of applications for Maximum Residue Levels (MRLs).
This is a new methodology aimed at fulfilling the legal requirement for decisions on applications for MRLs to take account of the known cumulative and synergistic effects when the methods to assess such effects become available. With methods now available, a significant level of knowledge has been built about the cumulative effects of pesticide residues in real life.
Our scientists have already used monitoring data to perform ‘retrospective’ risk assessments of the cumulative effects of pesticide residues on the nervous system, the thyroid, and an important aspect of embryonic development called craniofacial alterations. Assessments of cumulative effects on the kidney, the liver, and reproductive function are underway too.
Since the conditions needed to perform ‘prospective’ cumulative risk assessment (CRA) are now available, EFSA has developed a tentative approach based on discussions among Member States within the European Commission’s PAFF Committee. The French Agency for Food, Environmental and Occupational Health & Safety (ANSES) carried out tests, or 'mock assessments', exploring this tentative approach on EFSA's behalf. The reports indicate areas to address and list several recommendations to finetune the methodology before 'prospective CRA' using this approach can be carried out routinely.
Once a final approach is agreed by the PAFF Committee, prospective CRA will be part of the assessment process of applications for MRLs, further contributing to consumer safety.
Milestones - pesticides
2030
Target date for the completion of all needed cumulative risk assessments for pesticides residues.
2024
July
A new version of the Monte Carlo Risk Assessment (MCRA) platform marks a milestone in the development of the tool for use in the cumulative risk assessment (CRA) of pesticides. The update - version 10.1 now publicly available - includes significant developments to data connectivity, security, interoperability, and accessibility. Two external scientific reports outline the changes: the first report details the update of the MCRA platform; a second provides an update of the standard regulatory actions for retrospective CRA as well as the potential prospective CRA of pesticides using the MCRA platform.
May
The European Parliament asks EFSA to review the scientific literature on methodologies for assessing the long-term toxic and/or carcinogenic effects of pesticides, in particular as a result of interactions between the components in the chemical mixture. A new working group begins to carry out the review, the minutes are available online.
February
A new scientific report aims to speed up the CRA of pesticides and identification of target organs for assessment. It analyses 350 substances and 16 organs, identifying low priority substances, expected to contribute only marginally to cumulative risk, and high priority organs for future cumulative risk assessments. The report concludes that for 70% of organs considered, there is no need for additional risk assessments: combined exposure to pesticide residues is not likely to pose a health risk to consumers for those organs. In addition to the nervous system and the thyroid, for which EFSA has already performed CRAs, these are: reproductive function, foetal development, liver, kidney, male reproductive system, and hematopoietic system (the system producing blood cells).
EFSA is currently performing cumulative risk assessments on the kidneys, the liver and the reproductive function.
2023
October
Two external scientific reports explain how to use the latest methodology update of the MCRA web platform for CRA of pesticides and other chemicals. The release improves transparency, accessibility, and interoperability for risk assessors.
June
A technical workshop on risk assessment for plant protection products (PPPs) is attended by some 80 participants from 25 Member States, the European Commission, ECHA and EFSA who share experiences and current practices for assessing pesticide formulations, with the overall purpose of harmonising assessments at Member State and EU level.
2022
October
EFSA assesses the risks to pregnant women from dietary cumulative exposure to pesticide residues that have acute effects on embryo development. The conclusion is that, with varying degrees of certainty, exposure is below the threshold A dose or exposure below which adverse effects are not detected that triggers regulatory action.
2021
June - September
EFSA meets French MEPS to clarify the methods and data used to establish the safety of representative formulations of herbicides and pesticides. This follows a letter co-signed by more than 100 political leaders – MEPs, French deputies and French senators – to EFSA concerning its role in considering cumulative effects of substances in pesticide formulations under EU regulations on plant protection products.
- Letter by MEPs and EFSA’s reply
- Technical Meetings with MEPs:
February
The European Commission and EFSA publish an action plan to accelerate development and implementation of the methodology for cumulative risk assessment (CRA) of pesticides.
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 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
April
EFSA carries out two pilot cumulative risk assessments of pesticide residues: one considering two chronic effects on the thyroid system and another looking at two acute effects on the nervous system. 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.
2018
April
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.
2016
January
An RIVM-EFSA pilot study tests the Monte Carlo Risk Assessment software tool for carrying out exposure assessments of multiple pesticides.
2013
July
EFSA presents cumulative assessment group methodology for pesticides.
2008
May
The PPR Panel publishes a scientific opinion Opinions include risk assessments on general scientific issues, evaluations of an application for the authorisation of a product, substance or claim, or an evaluation of a risk assessment on the evaluation of existing methodologies for identification of new approaches to assess cumulative and synergistic risks from pesticides to human health.
2006
November
Milestones - general
2021
December
Following a public consultation and an international workshop, EFSA publishes new guidance from its Scientific Committee providing a framework for grouping chemicals for human risk assessment of combined exposure to multiple chemicals, and methods for identifying low priority chemicals to reduce the number of chemicals in assessments. For more details see FAQ (Q5).
October
EFSA holds an international workshop on scientific criteria for grouping chemicals into assessment groups and future challenges in risk assessment of chemical mixtures. Scientific advisory bodies from across the globe take part.
May
EFSA consults publicly on a draft guidance document (‘MixTox 2’) for grouping chemicals across the food safety area and prioritisation of groups of chemicals for human health risk assessment.
2019
March
EFSA finalises its ‘MixTox’ guidance document following a public consultation. The guidance equips its scientists with methodologies and tools to assess combined exposure to multiple chemicals. Related advice comes out on how to assess the genotoxicity of substances in chemical mixtures.
An EFSA research study from 2018 shows that overall in the EU awareness of chemical mixtures among the general public is quite low.
2017
January
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
October
Public consultation on proposed MixTox guidance scope and objectives.
May
2015
March
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
September
2013
July
Scientific report on international frameworks dealing with human risk assessment of combined exposure to multiple chemicals, reviewing current approaches and setting out future priorities.
FAQ
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 A sequence of events, identified by research, which explains an observed effect”. 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 A process to establish the response of organisms to a mixture of chemicals with similar toxicity. This involves adding up their individual effects to predict the likely impact of the overall mixture, response addition An approach to the risk assessment of mixtures of substances in which responses to each of the individual components are determined and added together in order to predict the response to the mixture as a whole. This approach is only valid if the individual components do not interact with each other, i.e. their effects are completely independent and interaction.
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.
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. 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.
In its 2021 guidance document, EFSA’s Scientific Committee provides a framework for grouping chemicals for human risk assessment of combined exposure to multiple chemicals and methods for identifying low priority chemicals to reduce the number of chemicals in assessments. The framework proposes:
- to apply hazard-driven criteria for the grouping of chemicals, using mechanistic information (how chemicals behave) on toxicity as the gold standard, i.e. a common mode of action or adverse outcome pathway A method of visualising a chain of events linked by causality that may lead to a harmful outcome for organisms or the environment, where available
- to group chemicals using a common adverse outcome, e.g. EFSA’s approach to the cumulative risk assessment of pesticides, when mechanistic data are not available
- to use toxicokinetic data (what happens to chemicals in an organism A living thing such as humans, animals, plants and microbes (e.g. bacteria, viruses)) for grouping, particularly for compounds that share common toxicologically relevant metabolites (breakdown products resulting from metabolism The total sum of physical and chemical processes that occur within living organisms)
- to use risk-based approaches for combined or single chemicals, and exposure-driven approaches as prioritisation methods
- to follow a structured weight of evidence A process in which all of the evidence relating to a decision is evaluated based on its strength and quality approach in all cases