Zebrafish embryo neonicotinoid developmental neurotoxicity in the FET test and behavioral assays.

The need for reliable, sensitive (developmental) neurotoxicity testing of chemicals has steadily increased. Given the limited capacities for routine testing according to accepted regulatory guidelines, there is potential risk to human health and the environment. Most toxicity studies are based on mammalian test systems, which have been questioned for low sensitivity, limited relevance for humans, and animal welfare considerations. This increased the need for alternative models, one of which is the zebrafish (Danio rerio) embryo. This study assessed selected neonicotinoids at sub-lethal concentrations for their effects on embryonic development and behavior. The fish embryo acute toxicity test (OECD TG 236) determined the lowest observable effective concentrations, which were used as the highest test concentrations in subsequent behavioral assays. In the FET test, no severe compound-induced sublethal effects were seen at < 100 µM. In the coiling assay, exposure to ≥ 1.25 µM nicotine (positive control) affected both the burst duration and burst count per minute, whereas ≥ 50 µM thiacloprid affected the mean burst duration. Exposure to ≥ 50 µM acetamiprid and imidacloprid induced significant alterations in both mean burst duration and burst count per minute. In the swimming assay, 100 µM acetamiprid induced alterations in the frequency and extent of movements, whilst nicotine exposure only induced non-significant changes. All behavioral changes could be correlated to findings in mammalian studies. Given the quest for alternative test methods of (developmental) neurotoxicity, zebrafish embryo behavior testing could be integrated into a future tiered testing scheme.

Guidance on risk assessment of nanomaterials to be applied in the food and feed chain: human and animal health.

The EFSA has updated the Guidance on risk assessment of the application of nanoscience and nanotechnologies in the food and feed chain, human and animal health. It covers the application areas within EFSA's remit, including novel foods, food contact materials, food/feed additives and pesticides. The updated guidance, now Scientific Committee Guidance on nano risk assessment (SC Guidance on Nano-RA), has taken account of relevant scientific studies that provide insights to physico-chemical properties, exposure assessment and hazard characterisation of nanomaterials and areas of applicability. Together with the accompanying Guidance on Technical requirements for regulated food and feed product applications to establish the presence of small particles including nanoparticles (Guidance on Particle-TR), the SC Guidance on Nano-RA specifically elaborates on physico-chemical characterisation, key parameters that should be measured, methods and techniques that can be used for characterisation of nanomaterials and their determination in complex matrices. The SC Guidance on Nano-RA also details aspects relating to exposure assessment and hazard identification and characterisation. In particular, nanospecific considerations relating to in vitro/in vivo toxicological studies are discussed and a tiered framework for toxicological testing is outlined. Furthermore, in vitro degradation, toxicokinetics, genotoxicity, local and systemic toxicity as well as general issues relating to testing of nanomaterials are described. Depending on the initial tier results, additional studies may be needed to investigate reproductive and developmental toxicity, chronic toxicity and carcinogenicity, immunotoxicity and allergenicity, neurotoxicity, effects on gut microbiome and endocrine activity. The possible use of read-across to fill data gaps as well as the potential use of integrated testing strategies and the knowledge of modes or mechanisms of action are also discussed. The Guidance proposes approaches to risk characterisation and uncertainty analysis.

Cumulative dietary risk characterisation of pesticides that have acute effects on the nervous system.

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.

Cumulative dietary risk characterisation of pesticides that have chronic effects on the thyroid.

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.

Guidance on the use of the Threshold of Toxicological Concern approach in food safety assessment.

The Scientific Committee confirms that the Threshold of Toxicological Concern (TTC) is a pragmatic screening and prioritisation tool for use in food safety assessment. This Guidance provides clear step-by-step instructions for use of the TTC approach. The inclusion and exclusion criteria are defined and the use of the TTC decision tree is explained. The approach can be used when the chemical structure of the substance is known, there are limited chemical-specific toxicity data and the exposure can be estimated. The TTC approach should not be used for substances for which EU food/feed legislation requires the submission of toxicity data or when sufficient data are available for a risk assessment or if the substance under consideration falls into one of the exclusion categories. For substances that have the potential to be DNA-reactive mutagens and/or carcinogens based on the weight of evidence, the relevant TTC value is 0.0025 µg/kg body weight (bw) per day. For organophosphates or carbamates, the relevant TTC value is 0.3 µg/kg bw per day. All other substances are grouped according to the Cramer classification. The TTC values for Cramer Classes I, II and III are 30 µg/kg bw per day, 9 µg/kg bw per day and 1.5 µg/kg bw per day, respectively. For substances with exposures below the TTC values, the probability that they would cause adverse health effects is low. If the estimated exposure to a substance is higher than the relevant TTC value, a non-TTC approach is required to reach a conclusion on potential adverse health effects.

Establishment of cumulative assessment groups of pesticides for their effects on the nervous system.

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.

Establishment of cumulative assessment groups of pesticides for their effects on the thyroid.

Cumulative assessment groups of pesticides have been established for two specific effects on the thyroid: firstly hypothyroidism, and secondly parafollicular cell (C-cell) hypertrophy, hyperplasia and neoplasia. 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 thyroid, 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.

Scientific opinion on pesticides in foods for infants and young children.

Following a request from the European Commission, the EFSA Panel on Plant Protection Products and their Residues (PPR Panel) prepared a scientific opinion to provide a comprehensive evaluation of pesticide residues in foods for infants and young children. In its approach to develop this scientific opinion, the EFSA PPR Panel took into account, among the others, (i) the relevant opinions of the Scientific Committee for Food setting a default maximum residue level (MRL) of 0.01 mg/kg for pesticide residues in foods for infants and young children; (ii) the recommendations provided by EFSA Scientific Committee in a guidance on risk assessment of substances present in food intended for infants below 16 weeks of age; (iii) the knowledge on organ/system development in infants and young children. For infants below 16 weeks of age, the EFSA PPR Panel concluded that pesticide residues at the default MRL of 0.01 mg/kg for food for infants and young children are not likely to result in an unacceptable exposure for active substances for which a health-based guidance value (HBGV) of 0.0026 mg/kg body weight (bw) per day or higher applies. Lower MRLs are recommended for active substances with HBGVs below this value. For infants above 16 weeks of age and young children, the established approach for setting HBGVs is considered appropriate. For infants below 16 weeks of age the approach may not be appropriate and the application of the EFSA guidance on risk assessment of substances present in food intended for infants below 16 weeks of age is recommended. The contribution of conventional food to the total exposure to pesticide residues is much higher than that from foods intended for infants and young children. Because of the increased intake of conventional food by young children, these have the highest exposure to pesticide residues, whereas infants 3-6 months of age generally have lower exposure. The impact of cumulative exposure to pesticide residues on infants and young children is not different from the general population and the EFSA cumulative risk assessment methodology is also applicable to these age groups. Residue definitions established under Regulation (EC) No 396/2005 are in general considered appropriate also for foods for infants and young children. However, based on a tier 1 analysis of the hydrolysis potential of pesticides simulating processing, the particular appropriateness of existing residue definitions for monitoring to cover processed food, both intended for infants and young children as well as conventional food, is questionable.

Scientific Opinion about the Guidance of the Chemical Regulation Directorate (UK) on how aged sorption studies for pesticides should be conducted, analysed and used in regulatory assessments.

The EFSA Panel on Plant Protection Products and their Residues reviewed the guidance on how aged sorption studies for pesticides should be conducted, analysed and used in regulatory assessment. The inclusion of aged sorption is a higher tier in the groundwater leaching assessment. The Panel based its review on a test with three substances taken from a data set provided by the European Crop Protection Association. Particular points of attention were the quality of the data provided, the proposed fitting procedure of aged sorption experiments and the proposed method for combining results obtained from aged sorption studies and lower-tier studies on degradation and adsorption. Aged sorption was a relevant process in all cases studied. The test revealed that the guidance could generally be well applied and resulted in robust and plausible results. The Panel considers the guidance suitable for use in the groundwater leaching assessment after the recommendations in this Scientific Opinion have been implemented, with the exception of the use of field data to derive aged sorption parameters. The Panel noted that the draft guidance could only be used by experienced users because there is no software tool that fully supports the work flow in the guidance document. It is therefore recommended that a user-friendly software tool be developed. Aged sorption lowered the predicted concentration in groundwater. However, because aged sorption experiments may be conducted in different soils than lower-tier degradation and adsorption experiments, it cannot be guaranteed that the higher tier predicts lower concentrations than the lower tier, while lower tiers should be more conservative than higher tiers. To mitigate this problem, the Panel recommends using all available higher- and lower-tier data in the leaching assessment. The Panel further recommends that aged sorption parameters for metabolites be derived only from metabolite-dosed studies. The formation fraction can be derived from parent-dosed degradation studies, provided that the parent and metabolite are fitted with the best-fit model, which is the double first-order in parallel model in the case of aged sorption.