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Vitamins and essential minerals are micronutrients that are required for the normal functioning of the human body. However, they may lead to adverse health effects if consumed in excess. A tolerable upper intake level (UL) is a science-based reference value that supports policy-makers and other relevant actors in managing the risks of excess nutrient intake. EFSA's principles for establishing ULs for vitamins and minerals were originally developed by the Scientific Committee on Food in 2000. This guidance from the EFSA Panel on Nutrition, Novel Foods and Food Allergens provides an updated framework for UL assessments. A draft was published in 2022 and underwent a 2-year piloting period. The present document incorporates revisions based on the experience gained through its practical implementation. It covers aspects related to the planning of the risk assessment (problem formulation and definition of methods) and its implementation (evidence retrieval, appraisal, synthesis, integration, uncertainty analysis). As in the previous framework, the general principles developed for the risk assessment of chemicals in food are applied, i.e. hazard identification, hazard characterisation, intake assessment, risk characterisation. Specific to nutrients are their biochemical and physiological roles and the specific and selective mechanisms that maintain the systemic homeostasis and accumulation of the nutrient in the body. Such considerations must also be taken into account when conducting risk assessments of nutrients., (© 2024 European Food Safety Authority. EFSA Journal published by Wiley‐VCH GmbH on behalf of European Food Safety Authority.)

Background: Studies suggest that greater exposure to natural vegetation (i.e., greenness) is associated with better mental health. However, there is limited research on greenness and mental health in the preconception period, a critical window of exposure in the life course. We investigated the associations of residential greenness with perceived stress and depressive symptoms using cross-sectional data from a cohort of pregnancy planners., Methods: From 2013 to 2019, we enrolled female-identified participants aged 21-45 years who were trying to conceive without the use of fertility treatment into a North American preconception cohort study (Pregnancy Study Online [PRESTO]). On the baseline questionnaire, participants completed the 10-item Perceived Stress Scale (PSS) and the Major Depression Inventory (MDI). Using geocoded addresses, we estimated residential greenness exposure via satellite imagery (Normalized Difference Vegetation Index [NDVI]) in a 100m buffer. We estimated mean differences and 95% confidence intervals for the association of greenness with perceived stress and depression scores using linear regression models, adjusting for individual and neighborhood sociodemographic characteristics. We also evaluated the extent to which associations were modified by urbanicity and neighborhood socioeconomic status (SES)., Results: Among 9718 participants, mean age was 29.9 years, 81.5% identified as non-Hispanic White, 25% had household incomes <$50,000, and mean neighborhood income was $61,932. In adjusted models, higher greenness was associated with lower stress and depression scores (mean difference per interquartile range in greenness: -0.20, 95% CI: -0.39, -0.01; and -0.19, 95% CI: -0.48, 0.10, respectively). The association was stronger among residents of lower SES neighborhoods in urban areas (PSS: -0.57, 95% CI: -1.00, -0.15; MDI: -0.72, 95% CI: -1.40, -0.04)., Conclusions: Higher greenness exposure was associated with lower stress and depressive symptoms among pregnancy planners, particularly in lower-SES neighborhoods., Competing Interests: Declaration of competing interest The authors declare the following financial interests/personal relationships which may be considered as potential competing interests: Lauren A. Wise reports financial support was provided by National Institutes of Health. Lauren A. Wise reports a relationship with AbbVie Inc that includes: consulting or advisory. Lauren A. Wise reports a relationship with Bill & Melinda Gates Foundation that includes: consulting or advisory. Lauren A. Wise has reported receiving in-kind donations for primary data collection in the Pregnancy Study Online (PRESTO) from Swiss Precision Diagnostics (home pregnancy tests) and Kindara.com (fertility tracking apps). If there are other authors, they declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier Inc. All rights reserved.)

Background: Modena's Local Health Authority (AUSL) is a public service with more than 5,000 employees. In its facilities, drinking water is available as tap water. However, disposable plastic bottles are also widely used, thus increasing plastic waste., Study Design and Methods: In the present study, we aimed to investigate employees' drinking habits through an ad hoc 10-item online questionnaire, which was administered in spring 2023., Results: Of the 584 participants (10.8% response rate), 75% of workers reported drinking less than 1.5 liters of water per day. In addition, 74% of workers brought water from home, while 62% used disposable plastic containers bought in the workplace or outside. When asked if they would appreciate a water refilling station in the workplace, whether that would induce them to consume less plastic and to drink more water, 91%, 82%, and 72% of workers said "yes", respectively. By installing water coolers, the estimated mean number of plastic bottles spared every day at the AUSL would be about 6,000., Conclusions: Our data shed light on most employees' perceived need for alternative sources of drinking water, not only in order to drink more for health benefits, but also to reduce plastic usage in favor of reusable, more environmentally friendly materials.

Background: During the COVID-19 pandemic, telemedicine had the opportunity to demonstrate its potential. In Italy, after an initial period of mistrust, it became clear that remote medicine can provide significant benefits for both healthcare professionals and patients. In the Local Health Unit of Modena (Emilia Romagna region, Northern Italy), great importance was placed on developing, promoting, and managing all telemedicine activities. In particular, it was decided to prioritize the activation of tele-visit services in accordance with the guidelines of the Emilia-Romagna region., Study Design: This case study aims to illustrate the activities planned and developed at the Local Health Authority of Modena for the implementation of the first service of this kind, the tele-visit service for outpatients suffering from type 1 diabetes mellitus, and to analyze data from the first 12 months of activity (from May 2023 to April 2024) to share reflections on the strengths and critical points encountered., Method: For the activation of tele-visits at the Local Health Authority of Modena, a dedicated working group was established with the mandate to manage all clinical, organizational, and IT aspects. Before starting the service, various preliminary activities were carried out, including selecting the clinical specialty to be activated, defining patient inclusion criteria, implementing IT systems, assessing clinical risks, preparing and distributing information materials, training healthcare personnel, and planning outpatient activities., Results: During the first year of experimental activation of the service (May 2023-April 2024), a total of 72 patients were enrolled in the project, with 103 tele-visits provided. The patients were predominantly women (67%), and the most represented age groups were 30-39 (26%) and 40-49 (21%). Half of the specialists in the Diabetology Service (9/19) participated in the initiative by providing tele-visits, most of whom were young and all of whom were women. The main issues identified through regularly scheduled meetings with professionals, to which the working group is seeking the most appropriate solutions, include poor adherence by many patients who still have doubts about this modality, the habit of many patients rescheduling appointments multiple times, a habit not diminished by this visit method, the non-uniform adherence of professionals, and uneven territorial diffusion of the service. Lastly, professionals reported various IT difficulties. Although the number of tele-visits was not high, the initiative has sparked the interest of several specialists, some of whom have already proposed activating other telemedicine services, with some even suggesting innovative new projects. The next steps will involve extending diabetes monitoring to pregnant women with gestational diabetes and developing tele-visit services for endocrinology, neurology, hematology, and gastroenterology., Conclusions: Implementing a tele-visit service in a Local Health Unit is a complex process. A thorough evaluation of the issues that emerged during the development phases and the initial delivery period can help us to act proactively to prevent the failure of future projects. Our evaluations suggest a need to act on two fronts: on one hand, we must organize further activities to promote telemedicine to both patients and healthcare providers, while on the other hand, we must work to resolve IT issues.

Background: Targeting effective strategies to prevent cognitive decline is key in the aging population. Some diets have been linked to a slower cognitive decline, potentially through reducing inflammation. We aimed at determining the effect of inflammatory dietary patterns (IDPs) on cognitive function in three population-based cohorts., Methods: In this longitudinal study, we analyzed data from the Canadian Longitudinal Study of Aging, CoLaus|PsyCoLaus and Rotterdam Study. Our analytical sample included participants over 55 years old with baseline data on cognition, dietary intake, and inflammatory markers. IDPs were derived for each cohort using reduced rank regression to reflect maximal variation in three inflammatory markers. We calculated scores of consumption of the IDPs, higher scores indicating more IDP consumption. We used inverse probability of treatment and censoring weights in the marginal structural models to estimate associations of higher versus lower quarters of consumption of an IDP on general cognition (Mini-Mental State Evaluation) and four cognitive domains (memory, verbal fluency, verbal learning and processing speed and executive function) during at least 3 years of follow-up., Results: We included 10,366 participants (mean age 68) followed-up for a mean of 5 years. Diet explained between 1 and 2% of the variation of the inflammatory markers. There were no differences in general cognition when comparing the highest to the lowest quarter of consumption of IDPs among the three cohorts. Mean differences for the four cognitive domains were of small magnitude across cohorts and not clinically relevant., Conclusion: Diet explained low variation in inflammatory markers. Consuming IDPs was not associated with mean differences in general or domain-specific cognitive function., Competing Interests: Conflict of interest The authors report that there are no disclosures relevant to this publication., (Copyright © 2024 The Author(s). Published by Elsevier Ltd.. All rights reserved.)

The European Commission requested EFSA to update the scientific guidance for the preparation of notifications for authorisation of traditional foods, previously developed following the adoption of Regulation (EU) 2015/2283 on novel foods. This guidance document provides advice on the scientific information needed to be submitted by applicants when submitting traditional food notifications pursuant to Article 14 and traditional food applications pursuant to Article 16 of Regulation (EU) 2015/2283. The safety of a traditional food should be substantiated by data on its composition, its experience of continued use and its proposed conditions of use. Its normal consumption should not be nutritionally disadvantageous. The applicant should integrate the information on the composition and the experience of continued use and provide a concise overall consideration on how this substantiates the history of safe use of the traditional food and how this relates to the proposed conditions of use for the EU. Potential health hazards identified on the basis of compositional data and/or data from the experience of continued use should be discussed. On the basis of the information provided, EFSA will assess the safety related to the consumption of the traditional food under the proposed conditions of use., Competing Interests: If you wish to access the declaration of interests of any expert contributing to an EFSA scientific assessment, please contact interestmanagement@efsa.europa.eu., (© 2024 European Food Safety Authority. EFSA Journal published by Wiley‐VCH GmbH on behalf of European Food Safety Authority.)

The European Commission requested EFSA to update the scientific guidance for the preparation of applications for authorisation of novel foods, previously developed following the adoption of Regulation (EU) 2015/2283 on novel foods. This guidance document provides advice on the scientific information needed to be submitted by the applicant towards demonstrating the safety of the novel food. Requirements pertain to the description of the novel food, production process, compositional data, specifications, proposed uses and use levels and anticipated intake of the novel food. Furthermore, information needed in sections on the history of use of the novel food and/or its source, absorption, distribution, metabolism, excretion, toxicological information, nutritional information and allergenicity is also described. The applicant should integrate and interpret the data presented in the different sections to provide their overall considerations on how the information supports the safety of the novel food under the proposed conditions of use. Where potential health hazards have been identified, they are to be discussed in relation to the anticipated intake of the novel food and the proposed target populations. On the basis of the information provided, EFSA will assess the safety of the novel food under the proposed conditions of use., Competing Interests: If you wish to access the declaration of interests of any expert contributing to an EFSA scientific assessment, please contact interestmanagement@efsa.europa.eu., (© 2024 European Food Safety Authority. EFSA Journal published by Wiley‐VCH GmbH on behalf of European Food Safety Authority.)

Following the adoption of Regulation (EU) No 1169/2011 on food information to consumers, the European Commission requested EFSA to update its 'Guidance on safety evaluation of sources of nutrients and bioavailability of the nutrient from the sources' regarding the scientific principles and data requirements for the scientific assessment of all new forms of micronutrients and to derive a conversion factor for new micronutrient sources or forms of micronutrients to be authorised for addition to foods, including food supplements. This guidance outlines the scientific principles that the NDA Panel will consider for the assessment of the safety and the quantification of the relative bioavailability of new sources of micronutrients, which applicants are requested to consider when preparing their applications. It also outlines the data requirements for dossiers. Applicants should integrate the data presented in different sections to provide their overall considerations on how the information provided supports the safety of the new micronutrient source and the quantification of its relative bioavailability compared to a reference source under the proposed conditions of use. As preparatory work for the development of this guidance, EFSA launched an Expert Survey and held an online workshop on 9th March 2023 inviting scientific input from stakeholders and scientific experts, the report of which is now available online in the EFSA's webpage., Competing Interests: If you wish to access the declaration of interests of any expert contributing to an EFSA scientific assessment, please contact interestmanagement@efsa.europa.eu., (© 2024 European Food Safety Authority. EFSA Journal published by Wiley‐VCH GmbH on behalf of European Food Safety Authority.)

Background: Exposure to environmental toxic metals represents a significant global public health concern. Many studies have reported that cadmium (Cd) exposure increases the risk of hypertension. Since the shape of such relation has not been well characterized, we assessed it by performing a systematic review and dose-response meta-analysis of human studies., Methods: We searched the literature through September 5, 2024 to identify papers related to Cd, hypertension, and blood pressure. Inclusion criteria were: observational design, adult population, assessment of exposure using Cd biomarkers, and availability of exposure category-specific risk estimates for hypertension. We performed a dose-response meta-analysis of the results from included studies., Results: Of the 18 studies published between 2006-2024, most had a cross-sectional design. Cd was measured in whole blood and/or urine in almost all studies, whereas only two studies measured Cd in serum. The dose-response meta-analysis indicated an almost linear relation between urinary Cd concentrations and hypertension risk with RR=1.18, 95% CI 1.02-1.37 at 2.0 μg/g creatinine compared with no exposure. In contrast, the association between blood Cd concentrations and hypertension risk was non-linear: there was a steep monotonic increase in risk for Cd concentrations below 2 μg/L, reaching a RR of 1.48 (95% CI 1.17-1.86) at 2.0 μg/L, after which a plateau seemed reached. We found similar trends when restricting to studies of Asian population, while when considering North American studies, hypertension risk increased above 1.0 μg/g creatinine., Conclusions: In this dose-response meta-analysis, risk of hypertension showed a non-linear positive association with blood Cd concentrations and a linear positive association with urinary Cd concentrations. Inconsistency in the shape of associations could relate to the different timing of exposure assessed by the biomarkers or the alteration Cd excretion at increasing exposure levels. Mitigation of Cd exposure is confirmed as a public health priority for chronic disease prevention., Competing Interests: Declaration of Competing Interest ☐ The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper. ☒ The authors declare the following financial interests/personal relationships which may be considered as potential competing interests: Dr. Lauren Wise receives in-kind donations from Kindara.com (fertility apps) and Swiss Precision Diagnostics (home pregnancy tests). She also serves as consultant for Gates Foundation and AbbVie, Inc. All of these relationships are for work unrelated to this manuscript. All other authors have nothing to disclosure., (Copyright © 2024. Published by Elsevier Inc.)

Objective: The study investigated maternal exposure to heavy metals from industrial sources during pregnancy as potential risk factors for childhood cancer., Methods: Cases ages 0-19 were identified from California Cancer Registry. Controls (20:1 ratio) were randomly selected from California Birth Registry, frequency-matched by birth year (1998-2016). We estimated maternal exposure to lead, nickel, and cobalt in ambient air from the Toxics Release Inventory. We examined "ever/never" and "high/low" exposures categorized by median exposure. Models were adjusted for maternal age, race/ethnicity, method of payment for prenatal care, neighborhood socioeconomic status, and urban/rural residence., Results: Among highly exposed persons, lead was associated with an increased teratoma risk (adjusted odds ratio [aOR]: 1.52; 95% confidence interval [CI]: 0.97, 2.37), whereas nickel was associated with an increased rhabdomyosarcoma risk (aOR: 1.45; 95% CI: 1.03, 2.04). Cobalt was associated with an increased glioma risk (aOR: 2.25; 95% CI: 1.39, 3.65) among ever-exposed persons. Inverse associations were found between Wilms tumor and nickel among the ever exposed and highly exposed (ever: aOR: 0.75; 95% CI: 0.59, 0.96; high: aOR: 0.64; 95% CI: 0.45, 0.93)., Conclusions: Findings suggest that air pollution from heavy metals released by industrial sources may elevate childhood cancer risk., Competing Interests: Heck, Chen, Van Deventer, Nianogo, Vinceti, Kang, Cockburn, and Federman have no relationships/conditions/circumstances that present potential conflict of interest., (Copyright © 2024 American College of Occupational and Environmental Medicine.)

Following a request from the European Commission, the EFSA Panel on Nutrition, Novel Foods and Food Allergens (NDA) was asked to deliver an opinion on glucosyl hesperidin (GH) as a novel food (NF) pursuant to Regulation (EU) 2015/2283. The NF, which is produced from hesperidin and dextrin by enzymatic reactions, is a powder consisting mainly of monoglucosyl hesperidin (MGH) and unreacted hesperidin (flavonoid), which account in total for up to 92.8% (on dry basis) of the product. The applicant proposed to use the NF in specific drinks and food supplements leading to a maximum intake of up to 364 mg per day for adults. The target population is the general population, except for food supplements for which the proposed target population is children from 1 year onwards and adults. Taking into consideration the composition of the NF and the proposed uses, the consumption of the NF is not nutritionally disadvantageous. There are no concerns regarding genotoxicity of the NF. Based on a 90-day oral toxicity study conducted with the NF, the Panel considers the NOAEL at the mid-dose group, i.e. ~ 1000 mg/kg body weight (bw) per day. By applying an uncertainty factor of 200, the resulting intake providing sufficient margin of exposure for humans would be 5 mg/kg bw per day. The available human intervention studies did not report clinically relevant changes in haematological or clinical chemistry parameters following the administration of GH/MGH at supplemental doses of up to 3 g/day for 12 weeks. Overall, the Panel considers that the margin of exposure (~ 200) between the intake of the NF at the proposed uses and use levels and the NOAEL from the 90-day study is sufficient. The Panel concludes that the NF, glucosyl hesperidin, is safe for the target population at the proposed uses and use levels., Competing Interests: If you wish to access the declaration of interests of any expert contributing to an EFSA scientific assessment, please contact interestmanagement@efsa.europa.eu., (© 2024 European Food Safety Authority. EFSA Journal published by Wiley‐VCH GmbH on behalf of European Food Safety Authority.)

Following a request from the European Commission, the EFSA Panel on Nutrition, Novel Foods and Food Allergens (NDA) was asked to deliver a scientific opinion on the revision of the tolerable upper intake level (UL) for vitamin E. As α -tocopherol is recognised as the only essential form of vitamin E, the Panel restricted its evaluation to α -tocopherol. Systematic reviews of the literature were conducted to assess evidence on priority adverse health effects of excess intake of vitamin E, namely risk of impaired coagulation and bleeding, cardiovascular disease and prostate cancer. The effect on blood clotting and associated increased risk of bleeding is considered as the critical effect to establish an UL for vitamin E. No new evidence has been published that could improve the characterisation of a dose-response. The ULs for vitamin E from all dietary sources, which were previously established by the Scientific Committee on Food, are retained for all population groups, i.e. 300 mg/day for adults, including pregnant and lactating women, 100 mg/day for children aged 1-3 years, 120 mg/day for 4-6 years, 160 mg/day for 7-10 years, 220 mg/day for 11-14 years and 260 mg/day for 15-17 years. A UL of 50 mg/day is established for infants aged 4-6 months and a UL of 60 mg/day for infants aged 7-11 months. ULs apply to all stereoisomeric forms of α -tocopherol. ULs do not apply to individuals receiving anticoagulant or antiplatelet medications (e.g. aspirin), to patients on secondary prevention for CVD or to patients with vitamin K malabsorption syndromes. It is unlikely that the ULs for vitamin E are exceeded in European populations, except for regular users of food supplements containing high doses of vitamin E., Competing Interests: If you wish to access the declaration of interests of any expert contributing to an EFSA scientific assessment, please contact interestmanagement@efsa.europa.eu., (© 2024 European Food Safety Authority. EFSA Journal published by Wiley‐VCH GmbH on behalf of European Food Safety Authority.)

Background: Alcohol consumption has been associated with higher blood pressure and an increased risk of hypertension. However, the possible exposure thresholds and effect-modifiers are uncertain., Methods: We assessed the dose-response relationship between usual alcohol intake and hypertension incidence in nonexperimental cohort studies. After performing a systematic literature search through February 20, 2024, we retrieved 23 eligible studies. We computed risk ratios and 95% CI of hypertension incidence using a nonlinear meta-analytic model based on restricted cubic splines, to assess the dose-response association with alcohol consumption., Results: We observed a positive and almost linear association between alcohol intake and hypertension risk with risk ratios of 0.89 (0.84-0.94), 1.11 (1.07-1.15), 1.22 (1.14-1.30), and 1.33 (1.18-1.49) for 0, 24, 36 and 48 g/d, respectively, using 12 g alcohol/d as the reference value. In sex-specific analyses, the association was almost linear in men over the entire range of exposure but only observed above 12 g/d in women, although with a steeper association at high levels of consumption compared with men. The increased risk of hypertension above 12 to 24 g alcohol/d was similar in Western and Asian populations and considerably greater in White than in Black populations, mainly due to the positive association in women at moderate-to-high intake., Conclusions: Overall, our results lend support to a causal association between alcohol consumption and risk of hypertension, especially above an alcohol intake of 12 g/d, and are consistent with recommendations to avoid or limit alcohol intake. Sex and ethnicity appear to be major effect-modifiers of such association., Competing Interests: None.

Following a request from the European Commission, the EFSA Panel on Nutrition, Novel Foods and Food Allergens (NDA) was asked to deliver an opinion on Acheta (A.) domesticus powder as a novel food (NF) pursuant to Regulation (EU) 2015/2283. The main components of the NF are protein, fat and dietary fibre (chitin). The Panel notes that the concentration of contaminants in the NF depends on the occurrence levels of these substances in the insect feed. The Panel further notes that there are no safety concerns regarding the stability of the NF if the NF complies with the proposed specification limits during its entire shelf-life. The NF has a high protein content, although the true protein content is overestimated when using the nitrogen-to-protein conversion factor of 6.25 due to the presence of non-protein nitrogen from chitin. The applicant proposed to use the NF as food ingredient in a number of food products. The target population proposed by the applicant is the general population. Considering the composition of the NF and the proposed conditions of use, the consumption of the NF is not nutritionally disadvantageous. The panel notes that no safety concerns arise from the toxicological information of A. domesticus . The panel considers that the consumption of the NF might trigger primary sensitisation to A. domesticus proteins and may cause allergic reactions in subjects allergic to crustaceans, mites and molluscs. Additionally, allergens from the feed may end up in the NF. The panel concludes that the NF is safe under the proposed uses and use levels., Competing Interests: If you wish to access the declaration of interests of any expert contributing to an EFSA scientific assessment, please contact interestmanagement@efsa.europa.eu., (© 2024 European Food Safety Authority. EFSA Journal published by Wiley‐VCH GmbH on behalf of European Food Safety Authority.)

ALS is characterized by a highly heterogeneous course, ranging from slow and uncomplicated to rapid progression with severe extra-motor manifestations. This study investigated ALS-related hospitalizations and their connection to clinical aspects, comorbidities, and prognosis. We performed a retrospective cohort study including patients residing in Modena, Italy, newly diagnosed between 2007 and 2017 and followed up until 31 December 2022. Data were obtained from the Emilia Romagna ALS registry, regional hospitals, and medical records. Among the 249 patients, there were 492 hospital admissions, excluding those for diagnostic purposes; 63% of the patients had at least one hospitalization post-diagnosis, with an average stay of 19.90 ± 23.68 days. Younger patients were more likely to be hospitalized multiple times and experienced longer stays (44.23 ± 51.71 days if <65 years; 26.46 ± 36.02 days if older, p < 0.001). Patients who were hospitalized at least once more frequently underwent gastrostomy (64.97%) or non-invasive (66.24%) and invasive (46.50%) ventilation compared to those never hospitalized (21.74%, 31.52%, 13.04%, respectively, p < 0.001 for all). Emergency procedures led to longer hospitalizations (62.84 ± 48.91 days for non-invasive ventilation in emergencies vs. 39.88 ± 46.46 days electively, p = 0.012). Tracheostomy-free survival was not affected by hospitalizations. In conclusion, younger ALS patients undergo frequent and prolonged hospitalizations, especially after emergency interventions, although these do not correlate with reduced survival.

Amyotrophic lateral sclerosis (ALS) is a fatal neurodegenerative disease affecting the brain and spinal cord motor neurons. On 25 April 2023, the drug tofersen, an antisense oligonucleotide, received the US Food and Drug Administration approval for treating ALS in adults carrying mutations of the SOD1 gene. We aimed at assessing whether cerebrospinal fluid concentrations of selenium, an element of both toxicological and nutritional interest possibly involved in disease etiology and progression, are modified by tofersen administration. We determined concentrations of selenium species by anion exchange chromatography hyphenated to inductively coupled plasma-dynamic reaction cell-mass spectrometry and overall selenium by using inductively coupled plasma sector-field mass spectrometry, at baseline and 6 months after active tofersen treatment in ten Italian ALS patients carrying the SOD1 gene mutation. Concentrations of total selenium and many selenium species substantially increased after the intervention, particularly of inorganic (tetravalent and hexavalent) selenium and of the organic species selenomethionine and a compound co-eluting with the selenocystine standard. Overall, these findings suggest that tofersen treatment markedly alters selenium status and probably the redox status within the central nervous system, possibly due to a direct effect on neurons and/or the blood-brain barrier. Further studies are required to investigate the biological and clinical relevance of these findings and how they might relate to the pharmacological effects of the drug and to disease progression., (© 2024. The Author(s).)

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., Competing Interests: If you wish to access the declaration of interests of any expert contributing to an EFSA scientific assessment, please contact interestmanagement@efsa.europa.eu., (© 2024 European Food Safety Authority. EFSA Journal published by Wiley‐VCH GmbH on behalf of European Food Safety Authority.)

Following an application from Egde Pharma Sp. z o.o, submitted for authorisation of a health claim pursuant to Article 13(5) of Regulation (EC) No 1924/2006 via the Competent Authority of Poland, the EFSA Panel on Nutrition, Novel Foods and Food Allergens (NDA) was asked to deliver an opinion on the scientific substantiation of a health claim related to citicoline and memory. The Panel considers that the food, citicoline (cytidine 5-diphosphocholine, CDP-Choline) inner salt, is sufficiently characterised. Improvement, maintenance or reduced loss of memory is a beneficial physiological effect for middle-aged or elderly adults encountering age-associated subjective memory impairment. The applicant identified three pertinent human intervention studies in healthy individuals that investigated the effect of citicoline on memory. In weighing the evidence, the Panel took into account that only one randomised controlled trial in healthy participants showed a beneficial effect of citicoline on episodic memory when consumed at doses of 500 mg/day for 12 weeks, whereas this effect has not been observed in another study using citicoline at doses of 1 g/day for 3 months or supported by data obtained in patients with dementia using doses of 1 g/day for 12 weeks and 12 months. No convincing evidence of a plausible mechanism by which citicoline or any of its components (in addition to their endogenous synthesis) could exert an effect on memory in humans has been provided. The Panel concludes that a cause-and-effect relationship has not been established between the consumption of citicoline (CDP-Choline) inner salt and improvement, maintenance or reduced loss of memory in middle-aged or elderly adults encountering age-associated subjective memory impairment., Competing Interests: If you wish to access the declaration of interests of any expert contributing to an EFSA scientific assessment, please contact interestmanagement@efsa.europa.eu., (© 2024 European Food Safety Authority. EFSA Journal published by Wiley‐VCH GmbH on behalf of European Food Safety Authority.)

Following an application from Cárnicas Joselito S.A. pursuant to Article 14 of Regulation (EC) No 1924/2006 via the Competent Authority of Spain, the Panel on Nutrition, Novel Foods and Food Allergens (NDA) was asked to deliver an opinion on the scientific substantiation of a health claim related to ' Joselito ham increases antioxidant substances in the body, reduces blood pressure and plasma triglycerides, decreases oxidative stress and prevents effect in diseases related to the cardiovascular and intestinal systems '. The scope of the application was proposed to fall under a health claim referring to disease risk reduction. The food constituent that is the subject of the health claim is Joselito, an Iberian ham characterised by a high content of oleic acid. The Panel considers that the food is sufficiently characterised. The Panel considers that lowering of LDL-cholesterol concentration and blood pressure is a beneficial effect by decreasing the risk of coronary heart disease. Upon a request from EFSA, the applicant identified one human intervention study as being pertinent to the claim. However, due to methodological limitations, the Panel considers that no conclusions can be drawn from this study for the scientific substantiation of the claim. The Panel notes that no human intervention studies from which conclusions could be drawn for the scientific substantiation of the claim were provided by the applicant. The Panel concludes that a cause and effect relationship has not been established between the intake of Joselito® ham and the reduction of LDL-cholesterol concentration or blood pressure., Competing Interests: If you wish to access the declaration of interests of any expert contributing to an EFSA scientific assessment, please contact interestmanagement@efsa.europa.eu., (© 2024 European Food Safety Authority. EFSA Journal published by Wiley‐VCH GmbH on behalf of European Food Safety Authority.)

Background: Studies have shown that the prevalence of all-variants Alzheimer's disease (AD) and frontotemporal dementia (FTD) both increase with age, even before the age of 65. However, it is not known whether their different clinical presentations all increase in prevalence with age in the same way., Methods: We studied the prevalence of the different clinical presentations of young-onset AD and FTD by 5-year age groups in a population-based study identifying all dementia patients with a diagnosis of AD and FTD and symptoms onset before age 65 in the Modena province, Italy. By using regression models of cumulative occurrences, we also estimated age-specific prevalence and compared the growth curves of the clinical presentations., Results: The prevalence of all-variants AD increased with age, from 18/1,000,000 in the 40-44 age group to 1411/1,000,000 in the 60-64 age group. The prevalence of all-variants FTD also increased with age, from 18/1,000,000 to 866/1,000,000. An estimation of age-specific prevalence functions of each clinical presentation showed that atypical non-amnestic AD and aphasic FTD grew the most in early ages, followed by the behavioural variant of FTD (bvFTD). Then, around the age of 60, amnestic AD took over and its age-specific prevalence continued to increase disproportionally compared to all the other clinical variants of AD and FTD, which, instead, started to decrease in prevalence., Conclusions: Amnestic AD is the clinical presentation that increases the most with advancing age, followed by bvFTD, suggesting that there is a differential vulnerability to the effect of ageing within the same neurodegenerative disease., (© 2024. The Author(s).)

Following a request from the European Commission, the EFSA Panel on Nutrition, Novel Foods and Food Allergens (NDA) was asked to deliver an opinion on vitamin D 2 mushroom powder as a novel food (NF) pursuant to Regulation (EU) 2015/2283. The NF is produced from Agaricus bisporus mushroom powder that has been exposed to ultraviolet (UV) irradiation to induce the conversion of provitamin D 2 (ergosterol) to vitamin D 2 (ergocalciferol). The NF contains concentrations of vitamin D in the form of vitamin D 2 in the range of 245-460 μg/g. The information provided on the production process, composition and specifications of the NF does not raise safety concerns. The applicant intends to add the NF as an ingredient in a variety of foods and beverages in amounts that result in either 1.2 or 2.4 μg vitamin D 2 per 100 g or 100 mL of the food as consumed. The applicant also intends to add the NF in food supplements at a maximum of 15 μg vitamin D 2 /day for individuals above 1 year of age, as well as in foods for special medical purposes (FSMPs). The estimates for combined intake of vitamin D from the NF, the background diet and fortified foods, were below the ULs for vitamin D as established previously by the NDA Panel for children, adolescents and adults, i.e. 50 and 100 μg/day. The estimated combined vitamin D intake in infants (6-12 months) is also below the UL for vitamin D of 35 μg/day. The Panel considers that taking into account the composition of the NF and the proposed conditions of use, the consumption of the NF is not nutritionally disadvantageous for the proposed target population. The Panel concludes that the NF is safe under the proposed conditions of use., Competing Interests: If you wish to access the declaration of interests of any expert contributing to an EFSA scientific assessment, please contact interestmanagement@efsa.europa.eu., (© 2024 European Food Safety Authority. EFSA Journal published by Wiley‐VCH GmbH on behalf of European Food Safety Authority.)

At low medically-relevant concentrations, ozone serves as an oxidant with a wide spectrum of antimicrobial activity and the ability to promote healing and reduce inflammation. Despite providing therapeutic benefits in a range of diseases, certain adverse effects and contraindications of ozone treatment must be considered. These are primarily related to toxicity from inhalation and systemic types of administration and can be avoided by following relevant guidelines and recommendations. Ozone therapy has been implemented in a number of fields of dentistry and the most commonly used formulations for the oral cavity are gaseous ozone, ozonized water and ozonized oil. The biological mechanisms underlying the molecular effects of ozone have been increasingly reported, but currently remain largely unknown. The aim of the present review was to provide an overview of the mechanisms involved in ozone interaction with dental tissues. The present review focused on relevant evidence regarding the effect of ozone on dental tissues, including periodontal structures, dental cells, enamel and dentine, considering in vitro studies in addition to animal and human studies. A variety of biological mechanisms acting through multiple biochemical target pathways were reported to be responsible for the therapeutic effects of ozone. The main beneficial effects of ozone occurred in the following domains: antimicrobial activity, remineralization and microstructural changes of hard dental tissues, immunomodulation and biostimulation of dental and periodontal cells. Additional research could provide further insights into the use of ozone, increase its use for broader clinical applications and assist in the selection of targeted protocols., Competing Interests: The authors declare that they have no competing interests., (Copyright: © 2024 Veneri et al.)

Following a request from the European Commission, the EFSA Panel on Nutrition, Novel Foods and Food Allergens (NDA) was asked to deliver a scientific opinion on the tolerable upper intake level (UL) for iron. Systematic reviews were conducted to identify evidence regarding high iron intakes and risk of chronic diseases, adverse gastrointestinal effects and adverse effects of iron supplementation in infancy, young childhood and pregnancy. It is established that systemic iron overload leads to organ toxicity, but no UL could be established. The only indicator for which a dose-response could be established was black stools, which reflect the presence of large amounts of unabsorbed iron in the gut. This is a conservative endpoint among the chain of events that may lead to systemic iron overload but is not adverse per se. Based on interventions in which black stools did not occur at supplemental iron intakes of 20-25 mg/day (added to a background intake of 15 mg/day), a safe level of intake for iron of 40 mg/day for adults (including pregnant and lactating women) was established. Using allometric scaling (body weight 0.75 ), this value was scaled down to children and adolescents and safe levels of intakes between 10 mg/day (1-3 years) and 35 mg/day (15-17 years) were derived. For infants 7-11 months of age who have a higher iron requirement than young children, allometric scaling was applied to the supplemental iron intakes (i.e. 25 mg/day) and resulted in a safe level of supplemental iron intake of 5 mg/day. This value was extended to 4-6 month-old infants and refers to iron intakes from fortified foods and food supplements, not from infant and follow-on formulae. The application of the safe level of intake is more limited than a UL because the intake level at which the risk of adverse effects starts to increase is not defined., Competing Interests: If you wish to access the declaration of interests of any expert contributing to an EFSA scientific assessment, please contact interestmanagement@efsa.europa.eu., (© 2024 European Food Safety Authority. EFSA Journal published by Wiley‐VCH GmbH on behalf of European Food Safety Authority.)

Following two requests from the European Commission, the EFSA Panel on Nutrition, Novel Foods and Food Allergens (NDA) was asked to deliver a scientific opinion on the revision of the tolerable upper intake level (UL) for preformed vitamin A and β-carotene. Systematic reviews of the literature were conducted for priority adverse health effects of excess vitamin A intake, namely teratogenicity, hepatotoxicity and endpoints related to bone health. Available data did not allow to address whether β-carotene could potentiate preformed vitamin A toxicity. Teratogenicity was selected as the critical effect on which to base the UL for preformed vitamin A. The Panel proposes to retain the UL for preformed vitamin A of 3000 μg RE/day for adults. This UL applies to men and women, including women of child-bearing age, pregnant and lactating women and post-menopausal women. This value was scaled down to other population groups using allometric scaling (body weight 0.75 ), leading to ULs between 600 μg RE/day (infants 4-11 months) and 2600 μg RE/day (adolescents 15-17 years). Based on available intake data, European populations are unlikely to exceed the UL for preformed vitamin A if consumption of liver, offal and products thereof is limited to once per month or less. Women who are planning to become pregnant or who are pregnant are advised not to consume liver products. Lung cancer risk was selected as the critical effect of excess supplemental β-carotene. The available data were not sufficient and suitable to characterise a dose-response relationship and identify a reference point; therefore, no UL could be established. There is no indication that β-carotene intake from the background diet is associated with adverse health effects. Smokers should avoid consuming food supplements containing β-carotene. The use of supplemental β-carotene by the general population should be limited to the purpose of meeting vitamin A requirements., Competing Interests: If you wish to access the declaration of interests of any expert contributing to an EFSA scientific assessment, please contact interestmanagement@efsa.europa.eu., (© 2024 European Food Safety Authority. EFSA Journal published by Wiley‐VCH GmbH on behalf of European Food Safety Authority.)

Background: Maternal solvent exposure has been suspected to increase offspring cancer risk. The study aimed to evaluate the associations between maternal residential exposure to solvents from industrial pollution during pregnancy and childhood cancer., Methods: The present study included 15,744 cancer cases (aged 0-19 years at diagnosis) identified from California Cancer Registry and 283,141 controls randomly selected from California Birth Registry (20:1 frequency-matched by birth year: 1998-2016). We examined industrial releases of tetrachloroethylene and 1,1,1-trichloroethane within 3 km of the birth address, while we used a 5 km buffer for carbon disulfide. We calculated the total exposure from all linked Toxic Release Inventory sites during each index pregnancy and assigned "ever/never" and "high/low exposed/unexposed" exposure, using median values. We performed quadratic decay models to estimate cancer risks associated with maternal solvent exposure in pregnancy., Results: 1,1,1-Trichloroethane was associated with rhabdomyosarcoma (adjusted Odds Ratio (aOR): 1.96; 95% Confidence Interval (CI): 1.16, 3.32) in the "ever exposed" group. Ever exposure to carbon disulfide was associated with increased risks of medulloblastoma (OR = 1.85, 95% CI 1.01, 3.40) and ependymoma (OR = 1.63, 95% CI 0.97, 2.74)., Conclusions: Overall, our findings suggested maternal residential exposure to solvents from industrial sources might be associated with elevated childhood cancer risks., Competing Interests: Declaration of competing interest The authors declare they have no actual or potential competing financial interests., (Copyright © 2024 The Authors. Published by Elsevier GmbH.. All rights reserved.)

Dementia is a major neurologic syndrome characterized by severe cognitive decline, and it has a detrimental impact on overall physical health, leading to conditions such as frailty, changes in gait, and fall risk. Depending on whether symptoms occur before or after the age of 65, it can be classified as early-onset (EOD) or late-onset (LOD) dementia. The present study is aimed at investigating the role of cardiovascular factors on EOD and LOD risk in an Italian population. Using a case-control study design, EOD and LOD cases were recruited at the Modena Cognitive Neurology Centers in 2016-2019. Controls were recruited among caregivers of all the dementia cases. Information about their demographics, lifestyles, and medical history were collected through a tailored questionnaire. We used the odds ratio (OR) and 95% confidence interval (CI) to estimate the EOD and LOD risk associated with the investigated factors after adjusting for potential confounders. Of the final 146 participants, 58 were diagnosed with EOD, 34 with LOD, and 54 were controls. According to their medical history, atrial fibrillation was associated with increased disease risk (ORs 1.90; 95% CI 0.32-11.28, and 3.64; 95% CI 0.32-41.39 for EOD and LOD, respectively). Dyslipidemia and diabetes showed a positive association with EOD, while the association was negative for LOD. We could not evaluate the association between myocardial infarction and EOD, while increased risk was observed for LOD. No clear association emerged for carotid artery stenosis or valvular heart disease. In this study, despite the limited number of exposed subjects and the high imprecision of the estimates, we found positive associations between cardiovascular disease, particularly dyslipidemia, diabetes, and atrial fibrillation, and EOD., Competing Interests: G.B. reported speaker&rsquo;s fees of small amounts from Bayer, Boston, BMS, Daiichi-Sankyo, Janssen, and Sanofi outside of the present work. The other authors declare no conflicts of interest. The funders had no role in the design of the study; in the collection, analyses, or interpretation of the data; in the writing of the manuscript; or in the decision to publish the results.

The Panel on Nutrition, Novel Foods and Food Allergens (NDA) was asked to deliver a scientific opinion on the safety of plant preparations from the root or rhizome of Rheum palmatum L., Rheum officinale Baill. and their hybrids, from the bark of Rhamnus frangula L. and Rhamnus purshiana DC. and from the leaf or fruit of Cassia senna L., which have been placed under Union scrutiny in Part C of Annex III in accordance with Article 8(4) of Regulation (EC) No 1925/2006. The NDA Panel reviewed the additional scientific data submitted during the period of scrutiny and the public consultation by interested parties. The pertinent scientific data were in vitro and in vivo genotoxicity studies on the plant preparations under consideration. All the results of the genotoxicity studies on plant preparations were negative. However, the plant preparations that were tested in the submitted studies were not sufficiently characterised with respect to the content of total and individual hydroxyanthracene derivatives (HADs) and components other than HADs. The studies confirmed the presence of ■■■■■, known to be genotoxic in vivo, and ■■■■■, shown to be genotoxic in vitro. In line with the EFSA Scientific Committee statement on genotoxicity assessment of chemical mixtures, considering the presence of an in vivo genotoxic compound, the plant preparations used in these studies have to be considered of concern for genotoxicity. Thus, the safety of preparations containing HADs from the root or rhizome of Rheum palmatum L., Rheum officinale Baill. and their hybrids, from the leaf or fruit of Cassia senna L. and from the bark of Rhamnus frangula L. and Rhamnus purshiana DC. cannot be established based on the submitted studies., Competing Interests: If you wish to access the declaration of interests of any expert contributing to an EFSA scientific assessment, please contact interestmanagement@efsa.europa.eu., (© 2024 European Food Safety Authority. EFSA Journal published by Wiley‐VCH GmbH on behalf of European Food Safety Authority.)

Background: The world is currently facing a process of climate change, which may adversely impact human health in many different ways. The safety of food, water and urban environments is endangered by the consequences of climate change. Sea level and temperature rise, along with more frequent and longer heat waves, represent only a few of the effects of climate change. The increased risk of extreme climate events (e.g., cyclones, droughts and floods) is another serious public health issue. These adverse effects are enhanced in areas and countries not having the capacity to effectively deal with climate change., Study Design: We primarily aimed at summarizing the impacts of climate change on public health. A further aim was to identify the most concerning consequences of this phenomenon and the vulnerability factors that amplify the negative effects of climate change., Methods: PubMed and other literature databases were used as literature sources for this narrative review based on the search terms 'climate change' and 'diseases categories' up to January 2024, in order to assess the most recent and relevant scientific evidence about the relation between climate change and public health, identify knowledge gaps and priorities for future research. We also screened the websites of major agencies devoted to human health protection and environmental health., Results and Conclusions: Climate change appears to induce a broad spectrum of generally adverse effects on public health. It may increase the risk of infectious diseases, psychiatric disorders, cancer and other diseases. Currently, we are not effectively counteracting this phenomenon, since pollutant and greenhouse gas emissions have been increasing alongside temperatures. A host of measures are required in order to prevent and fight climate change and related health effects. These include the adoption of a holistic approach and the collaboration of different kinds of expertise in order to design more effective strategies. Special attention should be paid to those who live in disadvantaged countries, and those who are more vulnerable to the adverse health consequences of climate change.

Background: Several studies have documented an increased risk of leukemia among children exposed to magnetic fields from high-voltage power lines, with some evidence of dose-response relation. However, findings in some studies have been inconsistent, and data on the effects of different sources of exposure are lacking. In this study, we evaluated the relation of childhood leukemia risk to exposure to magnetic fields from transformer stations., Methods: We conducted a population-based case-control study in a pediatric population of two Northern Italian provinces of Modena and Reggio Emilia. We included 182 registry-identified childhood leukemia cases diagnosed during 1998-2019 and 726 population controls matched on sex, year of birth, and province of residence. We assessed exposure by calculating distance from childhood residence to the nearest transformer station within a geographical information system, computing disease odds ratios (ORs) and 95% confidence intervals (CIs) using conditional logistic regression, adjusting for potential confounders. We evaluated exposure using two buffers (15 m and 25 m radius) and assessed two case groups: leukemia (all subtypes) and acute lymphoblastic leukemia (ALL)., Results: Residing within 15 m of a transformer station (vs. ≥15 m) was not appreciably associated with risk of leukemia (all subtypes) or ALL. We found similar results using a less stringent exposure buffer (25 m). Among children aged ≥5 years, the adjusted ORs were 1.3 (95% CI 0.1-12.8) for leukemia and 1.3 (95% CI 0.1-12.4) for ALL using the 15 m buffer, while they were 1.7 (95% CI 0.4-7.0) for leukemia and 0.6 (95% CI 0.1-4.8) for ALL using the 25 m buffer., Conclusions: While we found no overall association between residential proximity to transformer stations and childhood leukemia, there was some evidence for elevated risk of childhood leukemia among children aged ≥5 years. Precision was limited by the low numbers of exposed children., Competing Interests: Declaration of competing interest The authors declare the following financial interests/personal relationships which may be considered as potential competing interests: Dr. Wise is a consultant for AbbVie Inc, and the Gates Foundation. Her institution also receives NIH funding for studies outside of this work. Finally, Dr. Wise receives in-kind donations for primary data collection in the PRESTO cohort (Swiss Precision Diagnostics and Kindara.com). All other authors declare that they have no competing interests., (Copyright © 2023 The Authors. Published by Elsevier Inc. All rights reserved.)

Exposure to toxic metals is a global public health threat. Among other adverse effects, exposure to the heavy metal cadmium has been associated with greater risk of cardiovascular disease (CVD). Nonetheless, the shape of the association between cadmium exposure and CVD risk is not clear. This systematic review summarizes data on the association between cadmium exposure and risk of CVD using a dose-response approach. We carried out a literature search in PubMed, Web of Science, and Embase from inception to December 30, 2023. Inclusion criteria were: studies on adult populations, assessment of cadmium exposure, risk of overall CVD and main CVD subgroups as endpoints, and observational study design (cohort, cross-sectional, or case-control). We retrieved 26 eligible studies published during 2005-2023, measuring cadmium exposure mainly in urine and whole blood. In a dose-response meta-analysis using the one-stage method within a random-effects model, we observed a positive association between cadmium exposure and risk of overall CVD. When using whole blood cadmium as a biomarker, the association with overall CVD risk was linear, yielding a risk ratio (RR) of 2.58 (95 % confidence interval-CI 1.78-3.74) at 1 μg/L. When using urinary cadmium as a biomarker, the association was linear until 0.5 μg/g creatinine (RR = 2.79, 95 % CI 1.26-6.16), after which risk plateaued. We found similar patterns of association of cadmium exposure with overall CVD mortality and risks of heart failure, coronary heart disease, and overall stroke, whereas for ischemic stroke there was a positive association with mortality only. Overall, our results suggest that cadmium exposure, whether measured in urine or whole blood, is associated with increased CVD risk, further highlighting the importance of reducing environmental pollution from this heavy metal., Competing Interests: Declaration of competing interest The authors declare the following financial interests/personal relationships which may be considered as potential competing interestsThe authors declare the following financial interests/personal relationships which may be considered as potential competing interests: Dr. Lauren Wise receives in-kind donations from Kindara.com (fertility apps) and Swiss Precision Diagnostics (home pregnancy tests). She also serves as consultant for Gates Foundation and AbbVie, Inc. All of these relationships are for work unrelated to this manuscript. All other authors have nothing to disclosure., (Copyright © 2024 The Authors. Published by Elsevier Ltd.. All rights reserved.)

Following a request from the European Commission, the EFSA Panel on Nutrition, Novel Foods and Food Allergens (NDA) was asked to deliver an opinion on the safety of magnesium l-threonate as a novel food (NF) pursuant to Regulation (EU) 2015/2283 and to address the bioavailability of magnesium from this source in the context of Directive 2002/46/EC. The NF, produced by chemical synthesis, is intended to be used as new source for magnesium in food supplements at a maximum intake level of 3000 mg per day by adults, except for pregnant and lactating women. This dose corresponds to ~ 2730 mg l-threonate and 250 mg magnesium, which also corresponds to the UL for supplemental magnesium from readily dissociable magnesium salts. Based on results obtained from a dissociation study, two rat studies and one human trial, the Panel considers that magnesium is bioavailable from the NF. The NF may contain up to 1% oxalic acid. The Panel considers that an additional exposure to oxalic acid, that is up to 30 mg daily from the NF, is not to be of safety concern. The Panel concludes that the NF is not nutritionally disadvantageous. In 2008, the EFSA ANS Panel concluded that a human intake of l-threonate of 2700 mg per day is safe. This intake is similar to the maximum intake of l-threonate from the NF under the maximum proposed uses, and the NDA Panel concurs with the ANS Panel that this intake is safe. The Panel considers that there are no concerns regarding the genotoxicity of the NF. The Panel concludes that the NF, Mg l-threonate, is safe under the proposed conditions of use. The Panel concludes that the NF is a source from which magnesium is bioavailable., Competing Interests: If you wish to access the declaration of interests of any expert contributing to an EFSA scientific assessment, please contact interestmanagement@efsa.europa.eu., (© 2024 European Food Safety Authority. EFSA Journal published by Wiley‐VCH GmbH on behalf of European Food Safety Authority.)

Following a request from the European Commission, the EFSA Panel on Nutrition, Novel Foods and Food Allergens (NDA) was asked to deliver an opinion on ashitaba sap as a novel food (NF) pursuant to Regulation (EU) 2015/2283. Ashitaba sap is collected from harvested stems of Angelica keiskei plants. The principal constituents of the sap with regard to the safety assessment are chalcones (1%-2.25%) and furanocoumarins (< 0.01%). The applicant proposed to use the NF in food supplements at a maximum dose of 780 mg per day. The target population is adults excluding pregnant and lactating women. Taking into consideration the composition of the NF and the proposed uses, the composition of the NF is not nutritionally disadvantageous. There are no concerns regarding genotoxicity of the NF. Based on a 90-day oral toxicity study performed with the product as intended to be placed on the market (30% ashitaba sap powder and 70% cyclodextrins), the Panel establishes a safe dose of 0.5 mg/kg body weight (bw) per day for the product as it is intended to be placed on the market. For the target population, i.e. adults, this safe dose corresponds to 35 mg per day of the product as it is intended to be placed on the market and 137 mg per day of the NF, which is lower than the use level proposed by the applicant. The Panel concludes that the NF is safe for the target population at intake levels up to 137 mg per day., Competing Interests: If you wish to access the declaration of interests of any expert contributing to an EFSA scientific assessment, please contact interestmanagement@efsa.europa.eu., (© 2024 European Food Safety Authority. EFSA Journal published by Wiley‐VCH GmbH on behalf of European Food Safety Authority.)

Dental caries in children is a frequent and debilitating condition, whose management is often challenging. The aim of this systematic review was to investigate the effectiveness of ozone applications for the treatment of caries in primary dentition. According to PRISMA guidelines, a systematic literature search was performed up to 6 January 2024. Clinical studies using ozone to treat caries of deciduous teeth were considered for inclusion. Out of the 215 records retrieved, seven studies were eventually included in the review, all of which used gaseous ozone. Four studies were judged at high risk of bias, two at low risk, and one of some concerns. The great heterogeneity of designs, outcomes, and protocols made it impossible to conduct a meta-analysis. Despite some limitations, the evidence yielded by the included studies suggests that ozone application, regardless of the protocol applied, is comparable to other interventions in terms of clinical outcomes and anti-bacterial activity, with no reported adverse effects and good patient acceptance. Therefore, ozone application may be a non-invasive approach to treat caries in primary dentition, especially in very young and poorly cooperative patients. Further standardized and rigorous studies are, however, needed to identify the best clinical protocols for this specific field.

Following a request from the European Commission, the EFSA Panel on Nutrition, Novel Foods and Food Allergens (NDA) was asked to deliver an opinion on the extension of use of isomalto-oligosaccharide (IMO) as a novel food (NF) pursuant to Regulation (EU) 2015/2283. The NF consists of glucose oligomers with degrees of polymerisation of 3-9, along with various amounts of mono- and disaccharides. The NF comes in both syrup and powder form. The applicant intends to extend the current uses of the NF as an ingredient in several foods, and use the NF in food supplements aimed at the general population older than 10 years of age. The information provided on the manufacturing process, composition and specifications of the NF is sufficient and does not raise safety concerns. Along with literature data, the applicant carried out a tolerability study in adult volunteers with the NF at doses up to 120 g/day. The Panel concludes that this study provides reassurance that the NF is tolerable at doses of 120 g/day. Conservative intake estimates resulting from the use of the NF as an ingredient according to the currently authorised uses and new proposed uses result in a highest intake estimate in adolescents of 112 g/day at the 95th percentile, and reach 142 g/day in adolescents when the use as a food supplement is included. The Panel notes this amount is higher than the dose of 120 g/day for which tolerability has been demonstrated. However, considering the source, compositional characterisation, production process and nature of the NF, as well as the available nutritional and toxicological data on the NF, the Panel considers that the NF does not present safety concerns under the proposed conditions of use., Competing Interests: If you wish to access the declaration of interests of any expert contributing to an EFSA scientific assessment, please contact interestmanagement@efsa.europa.eu., (© 2024 European Food Safety Authority. EFSA Journal published by Wiley‐VCH GmbH on behalf of European Food Safety Authority.)