Conceptual basis for the development of guidance for the use of biomarkers of effect in regulatory risk assessment of chemicals.

This Scientific Report was carried out in the context of the self-task mandate (M-2023-00097) of the EFSA's Scientific Committee on 'Guidance on the use of biomarkers of effect in regulatory risk assessment of chemicals'. In the first phase, the project on biomarkers of effect started with a feasibility study (EFSA-Q-2024-00128), with the intention to look closer at definitions and descriptions of biomarkers of effect, as well as to explore several concepts related to the context of application and other scientific principles to be further considered for its development. In addition, relevant activities, initiatives and knowledge in this area were collected and analysed within a complementary mapping study.

Re-evaluation of silicon dioxide (E 551) as a food additive in foods for infants below 16 weeks of age and follow-up of its re-evaluation as a food additive for uses in foods for all population groups.

The present opinion is the follow-up of the conclusions and recommendations of the Scientific Opinion on the re-evaluation of silicon dioxide (E 551) as a food additive relevant to the safety assessment for all age groups. In addition, the risk assessment of silicon dioxide (E 551) for its use in food for infants below 16 weeks of age is performed. Based on the newly available information on the characterisation of the SAS used as E 551 and following the principles of the 2021 EFSA Guidance on Particle-TR, the conventional safety assessment has been complemented with nano-specific considerations.

Prioritisation of pesticides and target organ systems for dietary cumulative risk assessment based on the 2019-2021 monitoring cycle.

Aiming at accelerating the implementation of cumulative risk assessment to pesticide residues, this report describes a two-step prioritisation analysis, on individual pesticides and on target organ systems, that allows to identify (i) low-priority substances expected to have a marginal contribution to cumulative risk, and (ii) high priority organ systems to be addressed in future cumulative risk assessments. The analysis encompassed 350 substances and 36 raw primary commodities of plant origin surveyed in the monitoring cycle 2019-2021, carried out in 30 population groups, covering 3 age classes, and 17 EU countries. Probabilistic exposure calculations, for chronic and acute effects, were executed on the occurrence and consumption data by a two-dimensional procedure, modelling variability and uncertainty.

In vitro toxicological assessment of PhSeZnCl in human liver cells.

Unlabelled: Phenylselenenylzinc chloride (PhSeZnCl) is an air-stable selenolate, easily synthesizable through oxidative insertion of elemental zinc into the Se-halogen bond of the commercially available phenylselenyl chloride. PhSeZnCl was shown to possess a marked GPx-like activity both in NMR and in vitro tests, and to effectively react with cellular thiols, and was supposed for a potential use in the chemotherapy of drug-resistant cancers. However, activity of PhSeZnCl in hepatic cells has never been tested before now.

Risk Assessment of Combined Exposure to Multiple Chemicals at the European Food Safety Authority: Principles, Guidance Documents, Applications and Future Challenges.

Human health and animal health risk assessment of combined exposure to multiple chemicals use the same steps as single-substance risk assessment, namely problem formulation, exposure assessment, hazard assessment and risk characterisation. The main unique feature of combined RA is the assessment of combined exposure, toxicity and risk. Recently, the Scientific Committee of the European Food Safety Authority (EFSA) published two relevant guidance documents.

The use of adverse outcome pathways in the safety evaluation of food additives.

In the last decade, adverse outcome pathways have been introduced in the fields of toxicology and risk assessment of chemicals as pragmatic tools with broad application potential. While their use in the pharmaceutical and cosmetics sectors has been well documented, their application in the food area remains largely unexplored. In this respect, an expert group of the International Life Sciences Institute Europe has recently explored the use of adverse outcome pathways in the safety evaluation of food additives.

Characterizing the coverage of critical effects relevant in the safety evaluation of food additives by AOPs.

There is considerable interest in adverse outcome pathways (AOPs) as a means of organizing biological and toxicological information to assist in data interpretation and method development. While several chemical sectors have shown considerable progress in applying this approach, this has not been the case in the food sector. In the present study, safety evaluation reports of food additives listed in Annex II of Regulation (EC) No 1333/2008 of the European Union were screened to qualitatively and quantitatively characterize toxicity induced in laboratory animals.

Risk to human health related to the presence of perfluorooctane sulfonic acid and perfluorooctanoic acid in food.

The European Commission asked EFSA for a scientific evaluation on the risks to human health related to the presence of perfluorooctane sulfonic acid (PFOS) and perfluorooctanoic acid (PFOA) in food. Regarding PFOS and PFOA occurrence, the final data set available for dietary exposure assessment contained a total of 20,019 analytical results (PFOS n = 10,191 and PFOA n = 9,828). There were large differences between upper and lower bound exposure due to analytical methods with insufficient sensitivity.

Risk to human and animal health related to the presence of 4,15-diacetoxyscirpenol in food and feed.

4,15-Diacetoxyscirpenol (DAS) is a mycotoxin primarily produced by fungi and occurring predominantly in cereal grains. As requested by the European Commission, the EFSA Panel on Contaminants in the Food Chain (CONTAM) assessed the risk of DAS to human and animal health related to its presence in food and feed. Very limited information was available on toxicity and on toxicokinetics in experimental and farm animals.

Buccal micronucleus cytome assay in primary school children: A descriptive analysis of the MAPEC_LIFE multicenter cohort study.

Background: Recent data support the hypothesis that genetic damage occurring early in life during childhood can play an important role in the development of chronic diseases in adulthood, including cancer.

Objectives: The objective of this paper, part of the MAPEC_LIFE project, is to describe the frequency of micronuclei and meta-nuclear alterations in exfoliated buccal cells of 6-8year-old Italian children recruited in five Italian towns (i.e.

Update of the Scientific Opinion on opium alkaloids in poppy seeds.

Poppy seeds are obtained from the opium poppy L.). They are used as food and to produce edible oil.

Update of the risk assessment on 3-monochloropropane diol and its fatty acid esters.

The CONTAM Panel updated the assessment of the risks for human health related to the presence of 3-monochloropropane diol (3-MCPD) and its fatty acid esters in food published in 2016 in view of the scientific divergence identified in the establishment of the tolerable daily intake (TDI) in the Joint FAO/WHO Expert Committee on Food Additives and Contaminants (FAO/WHO) report published in 2017. In this update, dose-response analysis was performed following the recent EFSA Scientific Committee guidance on the use of benchmark dose (BMD) approach in risk assessment, and a review of available data on developmental and reproduction toxicity was included. The outcome of this review indicates that in rats short-term exposure to 3-MCPD above 1 mg/kg body weight (bw) per day can induce reduced sperm motility associated with reduced male fecundity.

In vitro toxicity evaluation of estragole-containing preparations derived from Foeniculum vulgare Mill. (fennel) on HepG2 cells.

Estragole, a common component of herbs and spices, is a wellknown genotoxic hepatocarcinogen in rodents, whereas its potential toxic effect in humans is still debated. In the European contest, one of the major sources of human exposure to this phytochemical is Foeniculum vulgare Mill. (fennel).

No evidence of DNA damage by co-exposure to extremely low frequency magnetic fields and aluminum on neuroblastoma cell lines.

Whether exposure to 50-60Hz extremely low frequency magnetic fields (ELF-MF) exerts neurotoxic effects is a debated issue. Analogously, the potential role of Aluminum (Al) in neurodegeneration is a matter of controversial debate. As all living organisms are exposed to ELF-MF and/or Al daily, we found investigating the early effects of co-exposure to ELF-MF and Al in SH-SY5Y and SK-N-BE-2 human neuroblastoma (NB) cells intriguing.

Dyes in aquaculture and reference points for action.

The European Commission requested EFSA to evaluate whether a series of dyes are covered by the 'Guidance on methodological principles and scientific methods to be taken into account when establishing Reference Points for Action (RPAs) for non-allowed pharmacologically active substances present in food of animal origin' and to which group they should be attributed according to this guidance. Although these substances are not registered for use in food-producing animals in the European Union, they may be used illegally in aquaculture for their antimicrobial properties. It was concluded that acriflavine, 3-aminoacridine, aminoacridine, basic blue 7, brilliant green, leucobrilliant green, C.

Socio-Economic and Environmental Factors Associated with Overweight and Obesity in Children Aged 6-8 Years Living in Five Italian Cities (the MAPEC_LIFE Cohort).

The prevalence of obesity among Italian children has reached such alarming levels as to require detailed studies of the causes of the phenomenon. A cross-sectional study was carried out in order to assess the weight status of 1164 Italian children aged 6-8 years (the Monitoring Air Pollution Effects on Children for Supporting Public Health Policy (MAPEC_LIFE) cohort) and to identify any associations between selected socio-economic and environmental factors and overweight/obesity. The data were obtained by means of a questionnaire given to parents, and any associations were examined by binomial logistic regression analyses.

Effects of the "PreveDi" lifestyle modification trial on metabolic syndrome.

Background: Metabolic syndrome (MetS) is a cluster of metabolic disorders that includes central obesity, hyperinsulinemia, hypercholesterolemia, hypertriglyceridemia and high blood pressure (BP). Statistical reports suggest that the prevalence of MetS has dramatically increased during the recent years and is considered a worldwide epidemic. MetS has been found to be associated with increased risk of all-cause mortality, cardiovascular diseases (CVD), type 2 diabetes mellitus, chronic kidney disease and some types of cancer.

Primary DNA damage in welders occupationally exposed to extremely-low-frequency magnetic fields (ELF-MF).

Background: Electric arc welding is known to involve considerable exposure to extremely-low-frequency magnetic fields (ELF-MF; 50 Hz). The aim of the present study was to evaluate individual exposure to ELF-MF during arc welding and to assess the eventually associated genotoxic hazard by evaluating primary DNA damage.

Methods: The study group comprised 21 electric arc welders (exposed) and 21 non-exposed control subjects (healthy blood donors).

Investigation of the cytotoxic, genotoxic, and apoptosis-inducing effects of estragole isolated from fennel (Foeniculum vulgare).

The present study was undertaken to evaluate, in the HepG2 human hepatoma cell line, the in vitro cytotoxic, genotoxic, and apoptotic activities of estragole (1), contained in the essential oil of Foeniculum vulgare (fennel) and suspected to induce hepatic tumors in susceptible strains of mice. Toward this end, an MTT cytotoxicity assay, a trypan blue dye exclusion test, a double-staining (acridine orange and DAPI) fluorescence viability assay, a single-cell microgel-electrophoresis (comet) assay, a mitochondrial membrane potential (Δψm) assay, and a DNA fragmentation analysis were conducted. In terms of potential genotoxic effects, the comet assay indicated that estragole (1) was not able to induce DNA damage nor apoptosis under the experimental conditions used.