Abstract The European Commission asked EFSA to update its 2018 risk assessment on polychlorinated dibenzo‐p‐dioxins and dibenzofurans (PCDD/Fs) and dioxin‐like polychlorinated biphenyls (DL‐PCBs) in feed and food, based on the 2022 WHO Toxic Equivalency Factors (WHO2022‐TEFs). A decrease in sperm concentrations as a consequence of early‐life exposure was still considered the critical effect in rodents and humans. This can only be prevented by ensuring sufficiently low exposure to PCDD/Fs and DL‐PCBs of future mothers. Using the WHO2022‐TEFs, the critical human study in the 2018 Opinion still showed a significant inverse association between PCDD/Fs and sperm concentration, but not when including DL‐PCBs. Therefore, this study was not used to derive a Tolerable Weekly intake (TWI). Instead, a developmental study with TCDD in rats was used to derive a TWI of 0.6 pg. WHO2022‐toxic equivalents (TEQ)/kg bw per week, based on decreased sperm production. Human studies were used as supporting evidence, including an evaluation of necessary uncertainty factors. Dietary exposure assessment based on occurrence data in food from the last decade, showed that using the new TEFs resulted in 27%–35% lower total‐TEQ exposure. Mean exposure (lower to upper bound) to PCDD/Fs and DL‐PCBs for European adult populations varied between 1.87 and 6.10 pg. WHO2022‐TEQ/kg bw per week, and at the P95 between 4.15 and 12.0 pg. WHO2022‐TEQ/kg bw per week. The CONTAM Panel concluded that exposure for European women of childbearing age raises a health concern for their sons at the mean (80%–90% certainty) and P95 (95%–99% certainty) exposure. Including uncertainties regarding the TEFs for DL‐PCBs decreased this certainty. Human milk data confirmed the exceedance of the TWI but to a lesser extent than dietary exposure. The change in TEFs does not affect the transfer rates of individual congeners but it could impact the transfer rates when using Total‐TEQ levels.

Abstract The European Commission asked EFSA to update its 2012 risk assessment on Emerging and Novel brominated flame retardants (BFRs) in food. Since the previous Opinion, further information was collected for a total of 27 BFRs. The CONTAM Panel concluded that TDBPP, DBPNG and TBNPA are considered genotoxic and carcinogenic. Based on positive in vitro mutagenicity in mammalian cells, DBE‐DBCH is considered genotoxic. EBTEBPI, DBDPE, PBB‐Acr and TTBP‐TAZ are not genotoxic. Insufficient or absent data precluded the Panel to conclude on the genotoxic potential of the remaining BFRs. Reproductive/developmental toxicity and/or neurotoxicity/neurodevelopmental effects were reported for DBNPG, BEH‐TEBP, EH‐TBB, DBDPE and TDBP‐TAZTO. Reference Points were identified for TDBPP, DBNPG, BEH‐TEBP, EH‐TBB, DBDPE and TDBP‐TAZTO. No health‐based guidance values could be derived for any of the BFRs. Occurrence data were submitted to EFSA for eight BFRs (BEH‐TEBP, EH‐TBB, BTBPE, DBDPE, HBB, PBEB, PBT, TBX). Dietary exposure could be estimated only for BTBPE and HBB, due to the lack of quantitative data for the other BFRs. However, no risk characterisation could be performed for these BFRs due to the lack of a Reference Point. Using the limited available information on dietary exposure estimates reported in the scientific literature, risk characterisation could be performed for BEH‐TEBP, EH‐TBB and DBDPE, and the CONTAM Panel concluded that dietary exposure does not raise a health concern. The Panel considered that the level of certainty was 90% or higher for most of the reported conclusions. Very limited or no information on hazard or exposure were available for HBCYD, TBCO, DBHCTD, HCTBPH, BDBP‐TAZTO, DBP‐TAZTO, OBTMPI, DBS, HEEHP‐TEBP, 4’‐PeBPO‐BDE208 or TTBNPP. Recommendations were formulated to address data gaps, including the need for access to original data, and for the collection of biomonitoring data, occurrence data in food, genotoxicity information and toxicological studies to support the identification of a Reference Point.

In 2022, the European Food Safety Authority (EFSA) conducted a dietary cumulative risk assessment for active substances of plant protection products on two types of craniofacial alterations: 1) craniofacial alterations due to abnormal skeletal development and 2) head soft tissue alterations and brain neural tube defects. These effects were selected based on developmental biology knowledge and a hypothetical teratogenic process. Cumulative risk assessment was conducted for 14 European populations of women in childbearing age. The dietary cumulative exposure was determined using individual consumption data collected under national food consumption surveys, and the calculations were based on occurrence data collected by Member States under their official monitoring programmes. A rigorous uncertainty analysis was performed using expert knowledge elicitation. Considering all sources of uncertainty, their dependencies, and differences between populations, it was concluded that the total margin of exposure (MOET) resulting from cumulative exposure to residues of pesticides is above 100 for both types of craniofacial alterations and therefore the threshold for regulatory consideration is not exceeded. For the head soft tissue alterations and brain neural tube defects the MOET was even above 500 while for the alterations due to abnormal skeletal development, it was found about as likely as not that the MOET is above 500 in most populations. These results need to be interpreted in the light of the conservatism of the hazard assessment methodology. This review is a summary of the EFSA report on a retrospective cumulative dietary risk assessment of craniofacial alterations by residues of pesticides published in 2022.

The European Commission asked EFSA to update its 2011 risk assessment on polybrominated diphenyl ethers (PBDEs) in food, focusing on 10 congeners: BDE-28, -47, -49, -99, -100, -138, -153, -154, -183 and ‑209. The CONTAM Panel concluded that the neurodevelopmental effects on behaviour and reproductive/developmental effects are the critical effects in rodent studies. For four congeners (BDE-47, -99, -153, -209) the Panel derived Reference Points, i.e. benchmark doses and corresponding lower 95% confidence limits (BMDLs), for endpoint-specific benchmark responses. Since repeated exposure to PBDEs results in accumulation of these chemicals in the body, the Panel estimated the body burden at the BMDL in rodents, and the chronic intake that would lead to the same body burden in humans. For the remaining six congeners no studies were available to identify Reference Points. The Panel concluded that there is scientific basis for inclusion of all 10 congeners in a common assessment group and performed a combined risk assessment. The Panel concluded that the combined margin of exposure (MOET) approach was the most appropriate risk metric and applied a tiered approach to the risk characterisation. Over 84,000 analytical results for the 10 congeners in food were used to estimate the exposure across dietary surveys and age groups of the European population. The most important contributors to the chronic dietary Lower Bound exposure to PBDEs were meat and meat products and fish and seafood. Taking into account the uncertainties affecting the assessment, the Panel concluded that it is likely that current dietary exposure to PBDEs in the European population raises a health concern.

This report summarises the training courses delivered under the contract OC/EFSA/AMU/2021/02 EKE: “Develop and conduct online training courses on Expert Knowledge Elicitation (EKE)”. The objective of the courses was to develop and conduct online training courses on applying the methodology described in the EFSA Guidance on Expert Knowledge Elicitation in Food and Feed Safety Risk Assessment” for EFSA staff and experts, as well as corresponding experts from EU member states. In addition to the three standard EKE methods (Sheffield, Delphi and Cooke), the training included a semi-formal method of EKE. All these methods may be used when EKE is performed within an existing EFSA working group to support uncertainty analysis as outlined in “The principles and methods behind EFSA's Guidance on Uncertainty Analysis in Scientific Assessment”. In total, 12 courses were organised: two on “Steering an Expert Knowledge Elicitation”, two on “Conduct of the Sheffield protocol for an EKE”, one on “Conduct of the Cooke protocol for an EKE”, one on “Conduct of the Delphi protocol for an EKE”, two on “Conduct of a Semi-formal EKE”, two on “Reporting an Expert Knowledge Elicitation” and two on “Writing an Evidence Dossier for an Expert Knowledge Elicitation”. The courses had in total 149 participants and received very good feedback from the participants with a mean value of 4.2 of 5 possible, considering all numerical questions in the feedback questionnaire. Recommendations for future activities on training EKE methodologies are provided.

Abstract The European Commission asked EFSA to update its 2012 risk assessment on brominated phenols and their derivatives in food, focusing on five bromophenols and one derivative: 2,4,6‐tribromophenol (2,4,6‐TBP), 2,4‐dibromophenol (2,4‐DBP), 4‐bromophenol (4‐BP), 2,6‐dibromophenol (2,6‐DBP), tetrabrominated bisphenol S (TBBPS), tetrabromobisphenol S bismethyl ether (TBBPS‐BME). Based on the overall evidence, the CONTAM Panel considered in vivo genotoxicity of 2,4,6‐TBP to be unlikely. Effects in liver and kidney were considered as the critical effects of 2,4,6‐tribromophenol (2,4,6‐TBP) in studies in rats. A BMDL10 of 353 mg/kg body weight (bw) per day for kidney papillary necrosis in male rats was identified and was selected as the reference point for the risk characterisation. The derivation of a health‐based guidance value was not considered appropriate due to major limitations in the toxicological database. Instead, the margin of exposure (MOE) approach was applied to assess possible health concerns. Around 78,200 analytical results for 2,4,6‐TBP in food were used to estimate dietary exposure for the European population. Considering the resulting MOE values, all far above an MOE of 6000 that does not raise a health concern, and accounting for the uncertainties affecting the exposure and hazard assessments, the CONTAM Panel concluded with at least 95% probability that the current dietary exposure to 2,4,6‐TBP does not raise a health concern. Due to lack of occurrence data, no risk assessment could be performed for breastfed or formula‐fed infants. No risk characterisation could be performed for any of the other brominated phenols and derivatives included in the assessment, due to lack of data both on the toxicity and occurrence.

Abstract The European Commission asked EFSA to update its 2011 risk assessment on tetrabromobisphenol A (TBBPA) and five derivatives in food. Neurotoxicity and carcinogenicity were considered as the critical effects of TBBPA in rodent studies. The available evidence indicates that the carcinogenicity of TBBPA occurs via non‐genotoxic mechanisms. Taking into account the new data, the CONTAM Panel considered it appropriate to set a tolerable daily intake (TDI). Based on decreased interest in social interaction in male mice, a lowest observed adverse effect level (LOAEL) of 0.2 mg/kg body weight (bw) per day was identified and selected as the reference point for the risk characterisation. Applying the default uncertainty factor of 100 for inter‐ and intraspecies variability, and a factor of 3 to extrapolate from the LOAEL to NOAEL, a TDI for TBBPA of 0.7 μg/kg bw per day was established. Around 2100 analytical results for TBBPA in food were used to estimate dietary exposure for the European population. The most important contributors to the chronic dietary LB exposure to TBBPA were fish and seafood, meat and meat products and milk and dairy products. The exposure estimates to TBBPA were all below the TDI, including those estimated for breastfed and formula‐fed infants. Accounting for the uncertainties affecting the assessment, the CONTAM Panel concluded with 90%–95% certainty that the current dietary exposure to TBBPA does not raise a health concern for any of the population groups considered. There were insufficient data on the toxicity of any of the TBBPA derivatives to derive reference points, or to allow a comparison with TBBPA that would support assignment to an assessment group for the purposes of combined risk assessment.

This Annex contains the occurrence data submitted to EFSA and dietary surveys per country and age group related to the Update of the risk assessment of polybrominated diphenyl ethers (PBDEs) in food.

This report summarises the trainings delivered under the contract OC/EFSA/SCER/2017/01-Lot 3. The objective of the trainings was to support understanding, uptake and implementation on the following EFSA Guidance: 1) Guidance on Uncertainty Analysis in Scientific Assessments, 2) Guidance on the use of the weight of evidence approach in scientific assessments and 3) Guidance on the assessment of the biological relevance of data in scientific assessments. In total, 14 trainings were organised: eight on uncertainty and six on weight of evidence and biological relevance. Several modalities were used for the trainings including face-to-face training, online synchronous training, e-learning, webinars, a workshop and a tutorial video. The trainings had in total 630 participants from EFSA´s Scientific Committee and Panels, EFSA working groups, EFSA Networks, EFSA staff, risk managers from DG SANTE and member state authorities and risk assessors from member state authorities. The trainings received very good feedback from the participants with a mean value of 4.3 of 5 possible for the concluding question in the feedback questionnaire: “Overall, are you satisfied with the course?”.

As part of its commitment to transparency, the European Food Safety Authority (EFSA) has been developing improved approaches to assessing uncertainty and expressing the degree of certainty in its scientific outputs. The objectives of this workshop were to review and improve the provision of this information by EFSA and its usefulness for risk managers, and to help risk managers to interpret and use it in their work. The workshop focussed on the non-regulated areas of EFSA’s work, chemical contaminants and biological hazards in food, plant health and animal health and welfare, and was attended by a total of 76 participants, of whom 28 were from DG SANTE and 22 were risk managers from EU Member State institutions. The workshop was held over two half days, one day focussed on uncertainty and decision-making and the other on uncertainty and communication. Each session began with an invited presentation by an eminent external speaker and an EFSA presentation on its approach, followed by separate breakout discussions for the four areas of EFSA’s work. Results from the breakout sessions were then presented and discussed in plenary. The workshop concluded with closing remarks from DG SANTE and EFSA, highlighting nine main points emerging from the discussions.

A retrospective cumulative risk assessment of dietary exposure to pesticide residues was conducted for chronic inhibition of acetylcholinesterase. The pesticides considered in this assessment were identified and characterised in a previous scientific report on the establishment of cumulative assessment groups of pesticides for their effects on the nervous system. The exposure assessments used monitoring data collected by Member States under their official pesticide monitoring programmes in 2016, 2017 and 2018, and individual food consumption data from 10 populations of consumers from different countries and from different age groups. Exposure estimates were obtained by means of a two-dimensional probabilistic model, which was implemented in SAS ® software. The characterisation of cumulative risk was supported by an uncertainty analysis based on expert knowledge elicitation. For each of the 10 populations, it is concluded with varying degrees of certainty that cumulative exposure to pesticides contributing to the chronic inhibition of acetylcholinesterase does not exceed the threshold for regulatory consideration established by risk managers.

An expert knowledge elicitation was conducted to address three tasks identified by EFSA's Animal Health and Welfare (AHAW) Panel: categorize outdoor farm types of pigs in EU MS according to the risk of African Swine Fever (ASF) introduction into these farms and the risk of ASF spread from these farms, rank biosecurity measures according to their potential to lower the risk of ASF introduction into these farms and the risk of ASF spread from these farms in ASF-affected countries, and propose improvements of biosecurity for outdoor pig farming categories and the control measures that should flank these in ASF-affected countries. The elicitation was conducted with four scientists with expertise in ASF epidemiology, biosecurity and outdoor farming practices and structures, including organic and backyard farming of pigs outdoors. The first task was addressed by eliciting estimates for the risk of new ASF outbreaks in the areas of interest in the coming year for two types of outdoor pig farms, specified by EFSA. As a worst-case scenario for assessment, the EKE considered areas of the EU where ASF is present in wild boar and in domestic pigs in indoor farms and, if outdoor farms were to be permitted in such areas, in domestic pigs in outdoor farms. The second task was addressed by developing a preliminary list of biosecurity measures, prioritising 7 measures in terms of expected effectiveness in reducing risk for each farm type, and then eliciting estimates of the effectiveness, feasibility and sustainability of each of the prioritised measures, considered separately. The third task was addressed by brainstorming of potential control measures to be considered in conjunction with improved biosecurity. The results are intended for consideration by the EFSA AHAW Panel when developing a Scientific Opinion on ASF and outdoor pig farming.

Mixtures of substances to which humans are exposed may lead to cumulative exposure and health effects. To study their effects, it is first necessary to identify a cumulative assessment group (CAG) of substances for risk assessment or hazard testing. Excluding substances from consideration before there is sufficient evidence may underestimate the risk. Conversely, including everything and treating the inevitable uncertainties using conservative assumptions is inefficient and may overestimate the risk, with an unknown level of protection. An efficient, transparent strategy is described to retain a large group, quantifying the uncertainty of group membership and other uncertainties. Iterative refinement of the CAG then focuses on adding information for the substances with high probability of contributing significantly to the risk. Probabilities can be estimated using expert opinion or derived from data on substance properties. An example is presented with 100 pesticides, in which the retain step identified a single substance to target refinement. Using an updated hazard characterisation for this substance reduced the mean exposure estimate from 0.43 to 0.28 μg kg-bw-1 day-1 and reduced the 99.99th percentile exposure from 24.9 to 5.1 μg kg-bw-1 day-1. Other retained substances contributed little to the risk estimates, even after accounting for uncertainty.

This final report summarises the objectives, activities and delivery, evaluation, and any future recommendations for each of the four trainings delivered under this contract. Sections are organised in chronological order consistent with the order in which trainings were delivered: Section 3 details the Sheffield course, Section 4 Semi-formal, Section 5 Delphi, and Section 6 Cooke. Section 7 provides overarching conclusions from across all trainings.

A retrospective acute cumulative risk assessment of dietary exposure to pesticide residues, supported by an uncertainty analysis based on expert knowledge elicitation, was conducted for two effects on the nervous system: brain and/or erythrocyte acetylcholinesterase inhibition, and functional alterations of the motor division. The pesticides considered in this assessment were identified and characterised in the scientific report on the establishment of cumulative assessment groups of pesticides for their effects on the nervous system. Cumulative exposure assessments were conducted through probabilistic modelling by EFSA and the Dutch National Institute for Public Health and the Environment (RIVM) using two different software tools and reported separately. These exposure assessments used monitoring data collected by Member States under their official pesticide monitoring programmes in 2014, 2015 and 2016 and individual consumption data from 10 populations of consumers from different countries and different age groups. This report completes the characterisation of cumulative risk, taking account of the available data and the uncertainties involved. For each of the 10 populations, it is concluded with varying degrees of certainty that cumulative exposure to pesticides that have the acute effects on the nervous system mentioned above does not exceed the threshold for regulatory consideration established by risk managers.

Abstract A retrospective chronic cumulative risk assessment of dietary exposure to pesticide residues, supported by an uncertainty analysis based on expert knowledge elicitation, was conducted for two effects on the thyroid, hypothyroidism and parafollicular cell (C‐cell) hypertrophy, hyperplasia and neoplasia. The pesticides considered in this assessment were identified and characterised in the scientific report on the establishment of cumulative assessment groups of pesticides for their effects on the thyroid. Cumulative exposure assessments were conducted through probabilistic modelling by EFSA and the Dutch National Institute for Public Health and the Environment (RIVM) using two different software tools and reported separately. These exposure assessments used monitoring data collected by Member States under their official pesticide monitoring programmes in 2014, 2015 and 2016 and individual consumption data from 10 populations of consumers from different countries and different age groups. This report completes the characterisation of cumulative risk, taking account of the available data and the uncertainties involved. For each of the 10 populations, it is concluded with varying degrees of certainty that cumulative exposure to pesticides that have the chronic effects on the thyroid mentioned above does not exceed the threshold for regulatory consideration established by risk managers.

Cumulative assessment groups of pesticides have been established for five effects on the nervous system: brain and/or erythrocyte acetylcholinesterase inhibition, functional alterations of the motor, sensory and autonomic divisions, and histological neuropathological changes in neural tissue. Sources of uncertainties resulting from the methodological approach and from the limitations in available data and scientific knowledge have been identified and considered. This report supports the publication of a scientific report on cumulative risk assessment to pesticides affecting the nervous system, in which all uncertainties identified for either the exposure assessment or the establishment of the cumulative assessment groups are incorporated into a consolidated risk characterisation.

The regulation of thyroid hormones (THs) production and physiological action is complex and can be adversely disrupted by a broad spectrum of chemicals at environmentally relevant concentrations through different and intricate mechanisms. This study reviews the current knowledge on how chemicals, in particular pesticides, can disrupt TH homeostasis. These include a) inhibition of TH biosynthesis in the thyroid follicular cells resulting in perturbation of the hypothalamic-pituitary-thyroid (HPT) axis; b) interference with TH transport proteins in the bloodstream; c) liver enzyme induction leading to increased inactivation and further excretion of TH from the body; d) interference with conversion of TH into the active form in peripheral tissues; e) interference with the transport of TH through cell membranes; and f) binding to intracellular TH receptors and further dysregulation of downstream gene expression sensitive to TH. Most pesticides included in the cumulative assessment group "hypothyroidism" by EFSA affect the HPT axis through upregulation of TH elimination pathways. A better understanding of the molecular mechanism behind the adverse effects, or at least the mode of action of each pesticide, reduces the uncertainty when the combined risk of dietary exposure to pesticides is assessed according to the dose-addition model.

This Guidance describes a two-phase approach for a fit-for-purpose method for the assessment of plant pest risk in the territory of the EU. Phase one consists of pest categorisation to determine whether the pest has the characteristics of a quarantine pest or those of a regulated non-quarantine pest for the area of the EU. Phase two consists of pest risk assessment, which may be requested by the risk managers following the pest categorisation results. This Guidance provides a template for pest categorisation and describes in detail the use of modelling and expert knowledge elicitation to conduct a pest risk assessment. The Guidance provides support and a framework for assessors to provide quantitative estimates, together with associated uncertainties, regarding the entry, establishment, spread and impact of plant pests in the EU. The Guidance allows the effectiveness of risk reducing options (RROs) to be quantitatively assessed as an integral part of the assessment framework. A list of RROs is provided. A two-tiered approach is proposed for the use of expert knowledge elicitation and modelling. Depending on data and resources available and the needs of risk managers, pest entry, establishment, spread and impact steps may be assessed directly, using weight of evidence and quantitative expert judgement (first tier), or they may be elaborated in substeps using quantitative models (second tier). An example of an application of the first tier approach is provided. Guidance is provided on how to derive models of appropriate complexity to conduct a second tier assessment. Each assessment is operationalised using Monte Carlo simulations that can compare scenarios for relevant factors, e.g. with or without RROs. This document provides guidance on how to compare scenarios to draw conclusions on the magnitude of pest risks and the effectiveness of RROs and on how to communicate assessment results.