Horizontal-to-Vertical Spectral Ratio of Ambient Vibration Obtained with Hilbert-Huang Transform.

The Horizontal-to-Vertical Spectral Ratio (HVSR) of ambient vibration measurements is a common tool to explore near surface shear wave velocity (Vs) structure. HVSR is often applied for earthquake risk assessments and civil engineering projects. Ambient vibration signal originates from the combination of a multitude of natural and man-made sources. Ambient vibration sources can be any ground motion inducing phenomena, e.g., ocean waves, wind, industrial activity or road traffic, where each source does not need to be strictly stationary even during short times. Typically, the Fast Fourier Transform (FFT) is applied to obtain spectral information from the measured time series in order to estimate the HVSR, even though possible non-stationarity may bias the spectra and HVSR estimates. This problem can be alleviated by employing the Hilbert-Huang Transform (HHT) instead of FFT. Comparing 1D inversion results for FFT and HHT-based HVSR estimates from data measured at a well studied, urban, permanent station, we find that HHT-based inversion models may yield a lower data misfit χ2 by up to a factor of 25, a more appropriate Vs model according to available well-log lithology, and higher confidence in the achieved model.

On the Utility of Horizontal-to-Vertical Spectral Ratios of Ambient Noise in Joint Inversion with Rayleigh Wave Dispersion Curves for the Large-N Maupasacq Experiment.

Horizontal-to-Vertical Spectral Ratios (HVSR) and Rayleigh group velocity dispersion curves (DC) can be used to estimate the shallow S-wave velocity (VS) structure. Knowing the VS structure is important for geophysical data interpretation either in order to better constrain data inversions for P-wave velocity (VP) structures such as travel time tomography or full waveform inversions or to directly study the VS structure for geo-engineering purposes (e.g., ground motion prediction). The joint inversion of HVSR and dispersion data for 1D VS structure allows characterising the uppermost crust and near surface, where the HVSR data (0.03 to 10s) are most sensitive while the dispersion data (1 to 30s) constrain the deeper model which would, otherwise, add complexity to the HVSR data inversion and adversely affect its convergence. During a large-scale experiment, 197 three-component short-period stations, 41 broad band instruments and 190 geophones were continuously operated for 6 months (April to October 2017) covering an area of approximately 1500km2 with a site spacing of approximately 1 to 3km. Joint inversion of HVSR and DC allowed estimating VS and, to some extent density, down to depths of around 1000m. Broadband and short period instruments performed statistically better than geophone nodes due to the latter's gap in sensitivity between HVSR and DC. It may be possible to use HVSR data in a joint inversion with DC, increasing resolution for the shallower layers and/or alleviating the absence of short period DC data, which may be harder to obtain. By including HVSR to DC inversions, confidence improvements of two to three times for layers above 300m were achieved. Furthermore, HVSR/DC joint inversion may be useful to generate initial models for 3D tomographic inversions in large scale deployments. Lastly, the joint inversion of HVSR and DC data can be sensitive to density but this sensitivity is situational and depends strongly on the other inversion parameters, namely VS and VP. Density estimates from a HVSR/DC joint inversion should be treated with care, while some subsurface structures may be sensitive, others are clearly not. Inclusion of gravity inversion to HVSR/DC joint inversion may be possible and prove useful.

Occupational risk assessment of glutaraldehyde through personal air monitoring in a hospital setting.

Glutaraldehyde is a high-efficiency disinfectant that has been included in the protocols of some hospitals for controlling the spread of SARS-CoV-2, together with sodium hypochlorite and quaternary ammonium disinfectants. However, exposure has been poorly studied in workplace settings, despite the association between glutaraldehyde and respiratory diseases and skin conditions in exposed workers. This study evaluated the magnitude of exposure associated with the use of glutaraldehyde in healthcare workers across various work areas of a first level of Hospital-Based Care in Colombia. Workers were classified into similar exposure groups (SEGs) based on work areas and tasks performed, and airborne concentrations of glutaraldehyde were measured in different work areas of each SEG through direct monitoring. The 95th percentile of glutaraldehyde concentrations in all SEGs studied exceeded the TLV-C immediately after use. Cleaning workers and nurses had the highest exposures to glutaraldehyde. Results indicate that workers were overexposed and highlight the need to implement controls to reduce exposure. The high-exposure levels also raise the need to consider glutaraldehyde substitution and adequate use of personal protective equipment (PPE).

Specific effects on the thyroid relevant for performing a dietary cumulative risk assessment of pesticide residues: 2024 update.

EFSA updated its previous work on the establishment of specific effects that are considered relevant for grouping pesticide residues targeting the thyroid and for performing the retrospective assessment of dietary cumulative risk (CRA). The two specific effects already selected in 2019 leading to the two cumulative assessment groups (CAGs) 'hypothyroidism' and 'C-cell hypertrophy, hyperplasia and neoplasia' were reconfirmed. Compared to 2019, the list of indicators that can be used to identify these specific effects was refined to only include histopathological changes. In a second phase of the work, data will be extracted on indicators of the specific effects from the dossiers on active substances (a.s.) used as plant protection products. The criteria for including a.s. into CAGs were also updated, together with the hazard characterisation methodology and the lines of evidence for assessing CAG-membership probabilities. The tasks related to the data extraction and the establishment of the CAGs on hypothyroidism and on C-cell hypertrophy, hyperplasia and neoplasia are beyond the scope of this report. This part of the CRA process has been outsourced and will be the subject of a separate report.

Statement on the toxicological properties and maximum residue levels of acetamiprid and its metabolites.

Acetamiprid is a pesticide active substance with insecticidal action whose approval was renewed by Commission Implementing Regulation (EU) 2018/113. In January 2022, the EFSA PPR Panel published a statement following a request from the European Commission to advise on human health or the environment based on new scientific evidence presented by France during the decision-making phase. In July 2022, by means of a further mandate received from the European Commission, EFSA was requested to provide advice if new information and any other scientific evidence that has become available since the assessment conducted for the renewal in 2018 warrant re-evaluation of (i) toxicological parameters used for the risk assessment of acetamiprid during the renewal process, including toxicological endpoints; (ii) the residue definition for acetamiprid in products of plant origin; and (iii) the safety of existing maximum residue levels (MRLs). Meanwhile, the applicant of acetamiprid in the EU submitted new toxicology studies regarding the toxicological profile of the metabolite IM-2-1. Furthermore, the European Commission was made aware that several recent publications in scientific literature were made available after the literature searches conducted by EFSA. As the new data could affect the advice that EFSA was expected to deliver through the 2022 mandate, EFSA was further requested to consider this information by means of a revised mandate received in September 2023. As regards re-evaluation of point (i) in this statement, this was addressed by an EFSA Working Group integrating all the available evidence. The results of the weight of evidence indicated that there are major uncertainties in the body of evidence for the developmental neurotoxicity (DNT) properties of acetamiprid and further data are therefore needed to come to a more robust mechanistic understanding to enable appropriate hazard and risk assessment. In view of these uncertainties, the EFSA WG proposed to lower the acceptable daily intake (ADI) and acute reference dose (ARfD) from 0.025 to 0.005 mg/kg body weight (per day). A revised residue definition for risk assessment was proposed for leafy and fruit crops as sum of acetamiprid and N-desmethyl-acetamiprid (IM-2-1), expressed as acetamiprid. Regarding pulses/oilseeds, root crops and cereals, the new data received did not indicate a need to modify the existing residue definition for risk assessment, which therefore remains as parent acetamiprid. Regarding the residue definition for enforcement, the available data did not indicate a need to modify the existing definition because acetamiprid is still a sufficient marker of the residues in all crop groups. Considering the new health-based guidance values derived in the present statement, a risk for consumer has been identified for 38 MRLs currently in place in the EU Regulation. Consequently, EFSA recommended to lower the existing MRLs for 38 commodities based on the assessment of fall-back Good Agricultural Practices received within an ad hoc data call. Some fall-back MRLs proposals require further risk management considerations.

Guidance on risk-benefit assessment of foods.

The EFSA Scientific Committee has updated its 2010 Guidance on risk-benefit assessment (RBA) of foods. The update addresses methodological developments and regulatory needs. While it retains the stepwise RBA approach, it provides additional methods for complex assessments, such as multiple chemical hazards and all relevant health effects impacting different population subgroups. The updated guidance includes approaches for systematic identification, prioritisation and selection of hazardous and beneficial food components. It also offers updates relevant to characterising adverse and beneficial effects, such as measures of effect size and dose-response modelling. The guidance expands options for characterising risks and benefits, incorporating variability, uncertainty, severity categorisation and ranking of different (beneficial or adverse) effects. The impact of different types of health effects is assessed qualitatively or quantitatively, depending on the problem formulation, scope of the RBA question and data availability. The integration of risks and benefits often involves value-based judgements and should ideally be performed with the risk-benefit manager. Metrics such as Disability-Adjusted Life Years (DALYs) and Quality-Adjusted Life Years (QALYs) can be used. Additional approaches are presented, such as probability of all relevant effects and/or effects of given severities and their integration using severity weight functions. The update includes practical guidance on reporting results, interpreting outcomes and communicating the outcome of an RBA, considering consumer perspectives and responses to advice.

Scientific Committee guidance on appraising and integrating evidence from epidemiological studies for use in EFSA's scientific assessments.

EFSA requested its Scientific Committee to prepare a guidance document on appraising and integrating evidence from epidemiological studies for use in EFSA's scientific assessments. The guidance document provides an introduction to epidemiological studies and illustrates the typical biases, which may be present in different epidemiological study designs. It then describes key epidemiological concepts relevant for evidence appraisal. This includes brief explanations for measures of association, exposure assessment, statistical inference, systematic error and effect modification. The guidance then describes the concept of external validity and the principles of appraising epidemiological studies. The customisation of the study appraisal process is explained including tailoring of tools for assessing the risk of bias (RoB). Several examples of appraising experimental and observational studies using a RoB tool are annexed to the document to illustrate the application of the approach. The latter part of this guidance focuses on different steps of evidence integration, first within and then across different streams of evidence. With respect to risk characterisation, the guidance considers how evidence from human epidemiological studies can be used in dose-response modelling with several different options being presented. Finally, the guidance addresses the application of uncertainty factors in risk characterisation when using evidence from human epidemiological studies.

Statement of the Scientific Panel on Plant Protection Products and their Residues (PPR Panel) on the design and conduct of groundwater monitoring studies supporting groundwater exposure assessments of pesticides.

Groundwater monitoring is the highest tier in the leaching assessment of plant protection products in the EU. The European Commission requested EFSA for a review by the PPR Panel of the scientific paper of Gimsing et al. (2019) on the design and conduct of groundwater monitoring studies. The Panel concludes that this paper provides many recommendations; however, specific guidance on how to design, conduct and evaluate groundwater monitoring studies for regulatory purposes is missing. The Panel notes that there is no agreed specific protection goal (SPG) at EU level. Also, the SPG has not yet been operationalised in an agreed exposure assessment goal (ExAG). The ExAG describes which groundwater needs to be protected, where and when. Because the design and interpretation of monitoring studies depends on the ExAG, development of harmonised guidance is not yet possible. The development of an agreed ExAG must therefore be given priority. A central question in the design and interpretation of groundwater monitoring studies is that of groundwater vulnerability. Applicants must demonstrate that the selected monitoring sites represent realistic worst-case conditions as specified in the ExAG. Guidance and models are needed to support this step. A prerequisite for the regulatory use of monitoring data is the availability of complete data on the use history of the products containing the respective active substances. Applicants must further demonstrate that monitoring wells are hydrologically connected to the fields where the active substance has been applied. Modelling in combination with (pseudo)tracer experiments would be the preferred option. The Panel concludes that well-conducted monitoring studies provide more realistic exposure assessments and can therefore overrule results from lower tier studies. Groundwater monitoring studies involve a high workload for both regulators and applicants. Standardised procedures and monitoring networks could help to reduce this workload.

Development of adverse outcome pathways relevant for the identification of substances having endocrine disruption properties Uterine adenocarcinoma as adverse outcome.

Development of adverse outcome pathways (AOPs) for uterine adenocarcinoma can provide a practical tool to implement the EFSA-ECHA Guidance (2018) for the identification of endocrine disruptors in the context of Regulations (EU) No 528/2012 and (EC) No 1107/2009. AOPs can give indications about the strength of the relationship between an adverse outcome (intended as a human health outcome) and chemicals (pesticides but not only) affecting the pathways. In this scientific opinion, the PPR Panel explored the development of AOPs for uterine adenocarcinoma. An evidence-based approach methodology was applied, and literature reviews were produced using a structured framework assuring transparency, objectivity, and comprehensiveness. Several AOPs were developed; these converged to a common critical node, that is increased estradiol availability in the uterus followed by estrogen receptor activation in the endometrium; therefore, a putative AOP network was considered. An uncertainty analysis and a probabilistic quantification of the weight of evidence have been carried out via expert knowledge elicitation for each set of MIEs/KEs/KERs included in individual AOPs. The collected data on the AOP network were evaluated qualitatively, whereas a quantitative uncertainty analysis for weight of the AOP network certainty has not been performed. Recommendations are provided, including exploring further the uncertainties identified in the AOPs and putative AOP network; further methodological developments for quantifying the certainty of the KERs and of the overall AOPs and AOP network; and investigating of NAMs applications in the context of some of the MIEs/KEs currently part of the putative AOP network developed.

Re-evaluation of the existing health-based guidance values for copper and exposure assessment from all sources.

Copper is an essential micronutrient and also a regulated product used in organic and in conventional farming pest management. Both deficiency and excessive exposure to copper can have adverse health effects. In this Scientific Opinion, the EFSA 2021 harmonised approach for establishing health-based guidance values (HBGVs) for substances that are regulated products and also nutrients was used to resolve the divergent existing HBGVs for copper. The tightly regulated homeostasis prevents toxicity manifestation in the short term, but the development of chronic copper toxicity is dependent on copper homeostasis and its tissue retention. Evidence from Wilson disease suggests that hepatic retention is indicative of potential future and possibly sudden onset of copper toxicity under conditions of continuous intake. Hence, emphasis was placed on copper retention as an early marker of potential adverse effects. The relationships between (a) chronic copper exposure and its retention in the body, particularly the liver, and (b) hepatic copper concentrations and evidence of toxicity were examined. The Scientific Committee (SC) concludes that no retention of copper is expected to occur with intake of 5 mg/day and established an Acceptable Daily Intake (ADI) of 0.07 mg/kg bw. A refined dietary exposure assessment was performed, assessing contribution from dietary and non-dietary sources. Background copper levels are a significant source of copper. The contribution of copper from its use as plant protection product (PPP), food and feed additives or fertilisers is negligible. The use of copper in fertilisers or PPPs contributes to copper accumulation in soil. Infant formula and follow-on formula are important contributors to dietary exposure of copper in infants and toddlers. Contribution from non-oral sources is negligible. Dietary exposure to total copper does not exceed the HBGV in adolescents, adults, elderly and the very elderly. Neither hepatic copper retention nor adverse effects are expected to occur from the estimated copper exposure in children due to higher nutrient requirements related to growth.

Guidance on protocol development for EFSA generic scientific assessments.

EFSA Strategy 2027 outlines the need for fit-for-purpose protocols for EFSA generic scientific assessments to aid in delivering trustworthy scientific advice. This EFSA Scientific Committee guidance document helps address this need by providing a harmonised and flexible framework for developing protocols for EFSA generic assessments. The guidance replaces the 'Draft framework for protocol development for EFSA's scientific assessments' published in 2020. The two main steps in protocol development are described. The first is problem formulation, which illustrates the objectives of the assessment. Here a new approach to translating the mandated Terms of Reference into scientifically answerable assessment questions and sub-questions is proposed: the 'APRIO' paradigm (Agent, Pathway, Receptor, Intervention and Output). Owing to its cross-cutting nature, this paradigm is considered adaptable and broadly applicable within and across the various EFSA domains and, if applied using the definitions given in this guidance, is expected to help harmonise the problem formulation process and outputs and foster consistency in protocol development. APRIO may also overcome the difficulty of implementing some existing frameworks across the multiple EFSA disciplines, e.g. the PICO/PECO approach (Population, Intervention/Exposure, Comparator, Outcome). Therefore, although not mandatory, APRIO is recommended. The second step in protocol development is the specification of the evidence needs and the methods that will be applied for answering the assessment questions and sub-questions, including uncertainty analysis. Five possible approaches to answering individual (sub-)questions are outlined: using evidence from scientific literature and study reports; using data from databases other than bibliographic; using expert judgement informally collected or elicited via semi-formal or formal expert knowledge elicitation processes; using mathematical/statistical models; and - not covered in this guidance - generating empirical evidence ex novo. The guidance is complemented by a standalone 'template' for EFSA protocols that guides the users step by step through the process of planning an EFSA scientific assessment.

Statement on the active substance flupyradifurone.

Flupyradifurone is a novel butenolide insecticide, first approved as an active substance for use in plant protection products by Commission Implementing Regulation (EU) 2015/2084. Following concerns that this substance may pose high risks to humans and the environment, the French authorities, in November 2020, asked the Commission to restrict its uses under Article 69 of Regulation (EC) No 1107/2009. To support this request, competent Authorities from France cited a series of literature papers investigating its hazards and/or exposure to humans and the environment. In addition, in June 2020, the Dutch Authorities notified the Commission, under Article 56 of Regulation (EC) No 1107/2009, of new information on flupyradifurone on the wild bee species Megachile rotundata. This notification is also referred to in the French notification on flupyradifurone. Consequently, the EFSA PPR Panel was mandated to quantify the likelihood of this body of evidence constituting proof of serious risks to humans or the environment. Therefore, the EFSA PPR Panel evaluated the likelihood of these studies indicating new or higher hazards and exposure to humans and the environment compared to previous EU assessments. A stepwise methodology was designed, including: (i) the initial screening; (ii) data extraction and critical appraisal based on the principles of OHAT/NTP; (iii) weight of evidence, including consideration of the previous EU assessments; (iv) uncertainty analysis, followed, whenever relevant, by an expert knowledge elicitation process. For the human health, only one study was considered relevant for the genotoxic potential of flupyradifurone in vitro. These data did not provide sufficient information to overrule the EU assessment, as in vivo studies already addressed the genotoxic potential of flupyradifurone. Environment: All available data investigated hazards in bee species. For honey bees, the likelihood of the new data indicating higher hazards than the previous EU assessment was considered low or moderate, with some uncertainties. However, among solitary bee species - which were not addressed in the previous EU assessment - there was evidence that Megachile rotundata may be disproportionately sensitive to flupyradifurone. This sensitivity, which may partially be explained by the low bodyweight of this species, was mechanistically linked to inadequate bodily metabolisation processes.

Statement on the active substance acetamiprid.

Acetamiprid is a pesticide active substance with insecticidal action currently under the third renewal (AIR3) of the Commission implementing regulation (EU) No 844/2012. Following concerns that this substance may pose high risks to humans and the environment, the French authorities asked the Commission to restrict its uses under Article 69 of Regulation (EC) No 1107/2009. To support this request, competent Authorities from France cited a series of literature papers investigating its hazards and/or exposure to humans and the environment. Consequently, the EFSA PPR Panel was mandated to advise on the likelihood that body of evidence would constitute proof of serious risks to humans or the environment. Therefore, the EFSA PPR Panel evaluated the likelihood of these studies indicating new or higher hazards and exposure to humans and the environment compared to previous EU assessments.A stepwise methodology was designed, including: (i) the initial screening; (ii) the data extraction and critical appraisal based on the principles of OHAT/NTP; (iii) the weight of evidence, including consideration of the previous EU assessments; (iv) the uncertainty analysis, followed, whenever relevant, by an expert knowledge elicitation process. For human health, no conclusive evidence of higher hazards compared to previous assessment was found for genotoxicity, developmental toxicity, neurotoxicity including developmental neurotoxicity and immunotoxicity. However, due to the lack of adequate assessment of the current data set, the PPR Panel recommends conducting an assessment of endocrine disrupting properties for acetamiprid in line with EFSA/ECHA guidance document for the identification of endocrine disruptors. For environment, no conclusive, robust evidence of higher hazards compared to the previous assessment was found for birds, aquatic organisms, bees and soil organisms. However, the potential of high inter-species sensitivity of birds and bees towards acetamiprid requires further consideration.

Evaluation of existing guidelines for their adequacy for the food and feed risk assessment of microorganisms obtained through synthetic biology.

EFSA was asked by the European Commission to evaluate synthetic biology (SynBio) developments for agri-food use in the near future and to determine whether or not they are expected to constitute potential new hazards/risks. Moreover, EFSA was requested to evaluate the adequacy of existing guidelines for risk assessment of SynBio and if updated guidance is needed. The scope of this Opinion covers food and feed risk assessment, the variety of microorganisms that can be used in the food/feed chain and the whole spectrum of techniques used in SynBio. This Opinion complements a previously adopted Opinion with the evaluation of existing guidelines for the microbial characterisation and environmental risk assessment of microorganisms obtained through SynBio. The present Opinion confirms that microbial SynBio applications for food and feed use, with the exception of xenobionts, could be ready in the European Union in the next decade. New hazards were identified related to the use or production of unusual and/or new-to-nature components. Fifteen cases were selected for evaluating the adequacy of existing guidelines. These were generally adequate for assessing the product, the production process, nutritional and toxicological safety, allergenicity, exposure and post-market monitoring. The comparative approach and a safety assessment per se could be applied depending on the degree of familiarity of the SynBio organism/product with the non-genetically modified counterparts. Updated guidance is recommended for: (i) bacteriophages, protists/microalgae, (ii) exposure to plant protection products and biostimulants, (iii) xenobionts and (iv) feed additives for insects as target species. Development of risk assessment tools is recommended for assessing nutritional value of biomasses, influence of microorganisms on the gut microbiome and the gut function, allergenic potential of new-to-nature proteins, impact of horizontal gene transfer and potential risks of living cell intake. A further development towards a strain-driven risk assessment approach is recommended.

Guidance on the use of the benchmark dose approach in risk assessment.

The Scientific Committee (SC) reconfirms that the benchmark dose (BMD) approach is a scientifically more advanced method compared to the no-observed-adverse-effect-level (NOAEL) approach for deriving a Reference Point (RP). The major change compared to the previous Guidance (EFSA SC, 2017) concerns the Section 2.5, in which a change from the frequentist to the Bayesian paradigm is recommended. In the former, uncertainty about the unknown parameters is measured by confidence and significance levels, interpreted and calibrated under hypothetical repetition, while probability distributions are attached to the unknown parameters in the Bayesian approach, and the notion of probability is extended to reflect uncertainty of knowledge. In addition, the Bayesian approach can mimic a learning process and reflects the accumulation of knowledge over time. Model averaging is again recommended as the preferred method for estimating the BMD and calculating its credible interval. The set of default models to be used for BMD analysis has been reviewed and amended so that there is now a single set of models for quantal and continuous data. The flow chart guiding the reader step-by-step when performing a BMD analysis has also been updated, and a chapter comparing the frequentist to the Bayesian paradigm inserted. Also, when using Bayesian BMD modelling, the lower bound (BMDL) is to be considered as potential RP, and the upper bound (BMDU) is needed for establishing the BMDU/BMDL ratio reflecting the uncertainty in the BMD estimate. This updated guidance does not call for a general re-evaluation of previous assessments where the NOAEL approach or the BMD approach as described in the 2009 or 2017 Guidance was used, in particular when the exposure is clearly lower (e.g. more than one order of magnitude) than the health-based guidance value. Finally, the SC firmly reiterates to reconsider test guidelines given the wide application of the BMD approach.

Opinion on the impact of non-monotonic dose responses on EFSA's human health risk assessments.

This Opinion assesses the biological relevance of the non-monotonic dose responses (NMDR) identified in a previous EFSA External Report (Beausoleil et al., 2016) produced under GP/EFSA/SCER/2014/01 and the follow-up probabilistic assessment (Chevillotte et al., 2017a,b), focusing on the in vivo data sets fulfilling most of the checkpoints of the visual/statistical-based analysis identified in Beausoleil et al. (2016). The evaluation was completed with cases discussed in EFSA assessments and the update of the scientific literature. Observations of NMDR were confirmed in certain studies and are particularly relevant for receptor-mediated effects. Based on the results of the evaluation, the Opinion proposes an approach to be applied during the risk assessment process when apparent non-monotonicity is observed, also providing advice on specific elements to be considered to facilitate the assessment of NMDR in EFSA risk assessments. The proposed approach was applied to two case studies, Bisphenol A and bis(2-ethylhexyl phthalate (DEHP) and these evaluations are reported in dedicated annexes. Considering the potential impact of NMDRs in regulatory risk assessment, the Scientific Committee recommends a concerted international effort on developing internationally agreed guidance and harmonised frameworks for identifying and addressing NMDRs in the risk assessment process.

Statement of the PPR Panel on a framework for conducting the environmental exposure and risk assessment for transition metals when used as active substances in plant protection products (PPP).

The European Commission asked the European Food Safety Authority (EFSA) to prepare a statement on a framework for the environmental risk assessment (ERA) of transition metals (e.g. iron and copper) used as active substances in plant protection products (PPPs). Non-degradability, essentiality and specific conditions affecting fate and behaviour as well as their toxicity are distinctive characteristics possibly not covered in current guidance for PPPs. The proposed risk assessment framework starts with a preliminary phase, in which monitoring data on transition metals in relevant environmental compartments are provided. They deliver the metal natural background and anthropogenic residue levels to be considered in the exposure calculations. A first assessment step is then performed assuming fully bioavailable residues. Should the first step fail, refined ERA can, in principle, consider bioavailability issues; however, non-equilibrium conditions need to be taken into account. Simple models that are fit for purpose should be employed in order to avoid unnecessary complexity. Exposure models and scenarios would need to be adapted to address environmental processes and parameters relevant to the fate and behaviour of transition metals in water, sediment and soils (e.g. speciation). All developments should follow current EFSA guidance documents. If refined approaches have been used in the risk assessment of PPPs containing metals, post-registration monitoring and controlled long-term studies should be conducted and assessed. Utilisation of the same transition metal in other PPPs or for other uses will lead to accumulation in environmental compartments acting as sinks. In general, it has to be considered that the prospective risk assessment of metal-containing PPPs can only cover a defined period as there are limitations in the long-term hazard assessment due to issues of non-degradability. It is therefore recommended to consider these aspects in any risk management decisions and to align the ERA with the goals of other overarching legislative frameworks.

Statement on the derivation of Health-Based Guidance Values (HBGVs) for regulated products that are also nutrients.

This Statement presents a proposal for harmonising the establishment of Health-Based Guidance Values (HBGVs) for regulated products that are also nutrients. This is a recurrent issue for food additives and pesticides, and may occasionally occur for other regulated products. The Statement describes the specific considerations that should be followed for establishing the HBGVs during the assessment of a regulated product that is also a nutrient. It also addresses the elements to be considered in the intake assessment; and proposes a decision tree for ensuring a harmonised process for the risk characterisation of regulated products that are also nutrients. The Scientific Committee recommends the involvement of the relevant EFSA Panels and units, in order to ensure an integrated and harmonised approach for the hazard and risk characterisation of regulated products that are also nutrients, considering the intake from all relevant sources.

Scientific Opinion of the Scientific Panel on Plant Protection Products and their Residues (PPR Panel) on testing and interpretation of comparative in vitro metabolism studies.

EFSA asked the Panel on Plant Protection Products and their residues to deliver a Scientific Opinion on testing and interpretation of comparative in vitro metabolism studies for both new active substances and existing ones. The main aim of comparative in vitro metabolism studies of pesticide active substances is to evaluate whether all significant metabolites formed in the human in vitro test system, as a surrogate of the in vivo situation, are also present at comparable level in animal species tested in toxicological studies and, therefore, if their potential toxicity has been appropriately covered by animal studies. The studies may also help to decide which animal model, with regard to a particular compound, is the most relevant for humans. In the experimental strategy, primary hepatocytes in suspension or culture are recommended since hepatocytes are considered the most representative in vitro system for prediction of in vivo metabolites. The experimental design of 3 × 3 × 3 (concentrations, time points, technical replicates, on pooled hepatocytes) will maximise the chance to identify unique (UHM) and disproportionate (DHM) human metabolites. When DHM and UHM are being assessed, test item-related radioactivity recovery and metabolite profile are the most important parameters. Subsequently, structural characterisation of the assigned metabolites is performed with appropriate analytical techniques. In toxicological assessment of metabolites, the uncertainty factor approach is the first alternative to testing option, followed by new approach methodologies (QSAR, read-across, in vitro methods), and only if these fail, in vivo animal toxicity studies may be performed. Knowledge of in vitro metabolites in human and animal hepatocytes would enable toxicological evaluation of all metabolites of concern, and, furthermore, add useful pieces of information for detection and evaluation of metabolites in different matrices (crops, livestock, environment), improve biomonitoring efforts via better toxicokinetic understanding, and ultimately, develop regulatory schemes employing physiologically based or physiology-mimicking in silico and/or in vitro test systems to anticipate the exposure of humans to potentially hazardous substances in plant protection products.

Guidance Document on Scientific criteria for grouping chemicals into assessment groups for human risk assessment of combined exposure to multiple chemicals.

This guidance document provides harmonised and flexible methodologies to apply scientific criteria and prioritisation methods for grouping chemicals into assessment groups for human risk assessment of combined exposure to multiple chemicals. In the context of EFSA's risk assessments, the problem formulation step defines the chemicals to be assessed in the terms of reference usually through regulatory criteria often set by risk managers based on legislative requirements. Scientific criteria such as hazard-driven criteria can be used to group these chemicals into assessment groups. In this guidance document, a framework is proposed to apply hazard-driven criteria for grouping of chemicals into assessment groups using mechanistic information on toxicity as the gold standard where available (i.e. common mode of action or adverse outcome pathway) through a structured weight of evidence approach. However, when such mechanistic data are not available, grouping may be performed using a common adverse outcome. Toxicokinetic data can also be useful for grouping, particularly when metabolism information is available for a class of compounds and common toxicologically relevant metabolites are shared. In addition, prioritisation methods provide means to identify low-priority chemicals and reduce the number of chemicals in an assessment group. Prioritisation methods include combined risk-based approaches, risk-based approaches for single chemicals and exposure-driven approaches. Case studies have been provided to illustrate the practical application of hazard-driven criteria and the use of prioritisation methods for grouping of chemicals in assessment groups. Recommendations for future work are discussed.