FAIR environmental and health registry (FAIREHR)- supporting the science to policy interface and life science research, development and innovation.

The environmental impact on health is an inevitable by-product of human activity. Environmental health sciences is a multidisciplinary field addressing complex issues on how people are exposed to hazardous chemicals that can potentially affect adversely the health of present and future generations. Exposure sciences and environmental epidemiology are becoming increasingly data-driven and their efficiency and effectiveness can significantly improve by implementing the FAIR (findable, accessible, interoperable, reusable) principles for scientific data management and stewardship. This will enable data integration, interoperability and (re)use while also facilitating the use of new and powerful analytical tools such as artificial intelligence and machine learning in the benefit of public health policy, and research, development and innovation (RDI). Early research planning is critical to ensuring data is FAIR at the outset. This entails a well-informed and planned strategy concerning the identification of appropriate data and metadata to be gathered, along with established procedures for their collection, documentation, and management. Furthermore, suitable approaches must be implemented to evaluate and ensure the quality of the data. Therefore, the 'Europe Regional Chapter of the International Society of Exposure Science' (ISES Europe) human biomonitoring working group (ISES Europe HBM WG) proposes the development of a FAIR Environment and health registry (FAIREHR) (hereafter FAIREHR). FAIR Environment and health registry offers preregistration of studies on exposure sciences and environmental epidemiology using HBM (as a starting point) across all areas of environmental and occupational health globally. The registry is proposed to receive a dedicated web-based interface, to be electronically searchable and to be available to all relevant data providers, users and stakeholders. Planned Human biomonitoring studies would ideally be registered before formal recruitment of study participants. The resulting FAIREHR would contain public records of metadata such as study design, data management, an audit trail of major changes to planned methods, details of when the study will be completed, and links to resulting publications and data repositories when provided by the authors. The FAIREHR would function as an integrated platform designed to cater to the needs of scientists, companies, publishers, and policymakers by providing user-friendly features. The implementation of FAIREHR is expected to yield significant benefits in terms of enabling more effective utilization of human biomonitoring (HBM) data.

Guidance on the preparation and submission of the notification and application for authorisation of traditional foods from third countries in the context of Regulation (EU) 2015/2283 (Revision 1).

[Table: see text] Following the adoption of Regulation (EU) 2015/2283 on Novel Foods, the European Commission requested EFSA to develop a scientific and technical guidance for the preparation and submission of notifications for traditional foods from third countries. This guidance presents a common format for the organisation of the information to be presented by applicant for the preparation of a well-structured dossier. The safety of a traditional food should be substantiated by reliable data on its composition, its experience of continued use and its proposed conditions of use. Its normal consumption should not be nutritionally disadvantageous. This guidance is also intended to support applicants in providing the type and quality of information EU Member States and EFSA need for the assessments of traditional foods from third countries. 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. Where potential health hazards have been identified on the basis of the composition and/or data from the experience of continued use, they 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. This guidance was originally adopted by the NDA Panel in 2016. It has been revised in 2020 to inform applicants of the new provisions introduced by Regulation (EC) No 178/2002, as amended by Regulation (EU) 2019/1381 on the transparency and sustainability of the EU risk assessment in the food chain.It is applicable to allnotifications and applications submitted as of 27 March 2021. The 2016 version remains applicable to notifications and applications submitted before 27 March 2021.

Risk-benefit in food safety and nutrition - Outcome of the 2019 Parma Summer School.

Risk-benefit assessment is the comparison of the risk of a situation to its related benefits, i.e. a comparison of scenarios estimating the overall health impact. The risk-benefit analysis paradigm mirrors the classical risk analysis one: risk-benefit assessment goes hand-in-hand with risk-benefit management and risk-benefit communication. The various health effects associated with food consumption, together with the increasing demand for advice on healthy and safe diets, have led to the development of different research disciplines in food safety and nutrition. In this sense, there is a clear need for a holistic approach, including and comparing all of the relevant health risks and benefits. The risk-benefit assessment of foods is a valuable approach to estimate the overall impact of food on health. It aims to assess together the negative and positive health effects associated with food intake by integrating chemical and microbiological risk assessment with risk and benefit assessment in food safety and nutrition. The 2019 Parma Summer School on risk-benefit in food safety and nutrition had the objective was to provide an opportunity to learn from experts in the field of risk-benefit approach in food safety and nutrition, including theory, case studies, and communication of risk-benefit assessments plus identify challenges for the future. It was evident that whereas tools and approaches have been developed, more and more case studies have been performed which can form an inherent validation of the risk-benefit approach. Executed risk-benefit assessment case studies apply the steps and characteristics developed: a problem formulation (with at least 2 scenarios), a tiered approach until a decision can be made, one common currency to describe both beneficial and adverse effects (DALYs in most instances). It was concluded that risk-benefit assessment in food safety and nutrition is gaining more and more momentum, while also many challenges remain for the future. Risk-benefit is on the verge of really enrolling into the risk assessment and risk analysis paradigm. The interaction between risk-benefit assessors and risk-benefit managers is pivotal in this, as is the interaction with risk-benefit communicators.

Addressing the risk of inadequate and excessive micronutrient intakes: traditional versus new approaches to setting adequate and safe micronutrient levels in foods.

Fortification of foods consumed by the general population or specific food products or supplements designed to be consumed by vulnerable target groups is amongst the strategies in developing countries to address micronutrient deficiencies. Any strategy aimed at dietary change needs careful consideration, ensuring the needs of at-risk subgroups are met whilst ensuring safety within the general population. This paper reviews the key principles of two main assessment approaches that may assist developing countries in deciding on effective and safe micronutrient levels in foods or special products designed to address micronutrient deficiencies, that is, the cut-point method and the stepwise approach to risk-benefit assessment. In the first approach, the goal is to shift population intake distributions such that intake prevalences below the Estimated Average Requirement (EAR) and above the Tolerable Upper Intake Level (UL) are both minimized. However, for some micronutrients like vitamin A and zinc, a narrow margin between the EAR and UL exists. Increasing their intakes through mass fortification may pose a dilemma; not permitting the UL to be exceeded provides assurance about the safety within the population but can potentially leave a proportion of the target population with unmet needs, or vice versa. Risk-benefit approaches assist in decision making at different micronutrient intake scenarios by balancing the magnitude of potential health benefits of reducing inadequate intakes against health risks of excessive intakes. Risk-benefit approaches consider different aspects of health risk including severity and number of people affected. This approach reduces the uncertainty for policy makers as compared to classic cut-point methods.

Vitamins and minerals: issues associated with too low and too high population intakes.

There is an ongoing increase in the availability of foods fortified with micronutrients and dietary supplements. This may result in differing intakes of micronutrients within the population and perhaps larger differences in intakes. Insight into population micronutrient intakes and evaluation of too low or too high intakes is required to see whether there are potential problems regarding inadequacy or excessive intakes. Too low population intakes are evaluated against an estimated average requirement; potential too high population intakes are evaluated against a tolerable upper intake level (UL). Additional health effects, seriousness, and incidence of these health effects are not considered but these can be taken into account in a benefit-risk assessment. Furthermore, authorities would like to regulate food fortification and supplementation in such a way that most of the population is not at risk of potentially high intakes. Several models are available for estimating maximum levels of micronutrients for food fortification and dietary supplements. Policy makers and risk managers need to decide how to divide the 'free space' between food fortification and/or dietary supplements, while protecting populations from adverse health effects.

Evaluation of the Dutch general exemption level for voluntary fortification with folic acid.

INTRODUCTION: Fortification with folic acid was prohibited in the Netherlands. Since 2007, a general exemption is given to fortify with folic acid up until a maximum level of 100 µg/100 kcal. This maximum level was based on a calculation model and data of adults only. The model requires parameters on intake (diet, supplements, energy) and on the proportion of energy that may be fortified. This study aimed to evaluate the model parameters considering the changing fortification market. In addition, the risk of young children exceeding the UL for folic acid was studied. METHODS: Folic acid fortified foods present on the Dutch market were identified in product databases and by a supermarket inventory. Together with data of the Dutch National Consumption Survey-Young Children (2005/2006) these inventory results were used to re-estimate the model parameters. Habitual folic acid intake of young children was estimated and compared to the UL for several realistic fortification scenarios. RESULTS: Folic acid fortified foods were identified in seven different food groups. In up to 10% of the population, the proportion of energy intake of folic acid fortified foods exceeded 10% - the original model parameter. The folic acid intake from food supplements was about 100 µg/day, which is lower than the intake assumed as the original model parameter (300 µg). In the scenarios representing the current market situation, a small proportion (<5%) of the children exceeded the UL. CONCLUSION: The maximum fortification level of 100 µg/100 kcal is sufficiently protective for children in the current market situation. In the precautionary model to estimate the maximum fortification levels, subjects with high intakes of folic acid from food and supplements, and high energy intakes are protected from too high folic acid intakes. Combinations of high intakes are low in this population. The maximum levels should be monitored and revised with increasing fortification and supplementation practices.

Application of the BRAFO tiered approach for benefit-risk assessment to case studies on dietary interventions.

The respective examples, described in this paper, illustrate how the BRAFO-tiered approach, on benefit-risk assessment, can be tested on a wide range of case studies. Various results were provided, ranging from a quick stop as the result of non-genuine benefit-risk questions to continuation through the tiers into deterministic/probabilistic calculations. The paper illustrates the assessment of benefits and risks associated with dietary interventions. The BRAFO tiered approach is tested with five case studies. In each instance, the benefit-risk approach is tested on the basis of existing evaluations for the individual effects done by others; no new risk or benefit evaluations were made. The following case studies were thoroughly analysed: an example of food fortification, folic acid fortification of flour, macronutrient replacement/food substitution; the isocaloric replacement of saturated fatty acids with carbohydrates; the replacement of saturated fatty acids with monounsaturated fatty acids; the replacement of sugar-sweetened beverages containing mono- and disaccharides with low calorie sweeteners and an example of addition of specific ingredients to food: chlorination of drinking water.

Functional foods and dietary supplements: products at the interface between pharma and nutrition.

It is increasingly recognized that most chronic diseases of concern today are multifactorial in origin. To combat such diseases and adverse health conditions, a treatment approach where medicines and nutrition complement each other may prove to be the most successful. Within nutrition, apart from (disease-related) dietetic regimes, an increasing number of functional foods and dietary supplements, each with their own health claim, are marketed. These food items are considered to be positioned between traditional foods and medicines at the so-called 'Pharma-Nutrition Interface'. This paper encompasses aspects related to the regulatory framework and health claims of functional foods and dietary supplements. The use of functional foods or dietary supplements may offer opportunities to reduce health risk factors and risk of diseases, both as monotherapy and in combination with prescription drugs. Nevertheless, the potential caveats of these products should not be overlooked. These caveats include the increased risk for food-drug interactions due to the elevated amounts of specific functional ingredients in the diet, and the stimulation of self-medication potentially resulting in lower adherence to drug therapy. Health technology assessments should be used more to compare the cost-effectiveness and benefit-risk ratios of drugs, functional foods and dietary supplements, and to evaluate the added value of functional foods or dietary supplements to drug therapy.

Impact of substituting added sugar in carbonated soft drinks by intense sweeteners in young adults in the Netherlands: example of a benefit-risk approach.

PURPOSE: Substituting added sugar in carbonated soft drinks with intense sweeteners may have potential beneficial, but also adverse health effects. This study assessed the benefits and risks associated with substituting added sugar in carbonated soft drinks with intense sweeteners in young adults in the Netherlands. METHODS: A tiered approach was used analogous to the risk assessment paradigm, consisting of benefit and hazard identification, exposure assessment and finally benefit and risk characterization and comparison. Two extreme scenarios were compared in which all carbonated soft drinks were sweetened with either intense sweeteners or added sugar. National food consumption survey data were used, and intake of added sugar and intense sweeteners was calculated using the food composition table or analytical data for sweetener content. RESULTS: Reduction in dental caries and body weight were identified as benefits of substituting sugar. The mean difference in total energy intake between the scenarios was 542 kJ per day in men and 357 kJ per day in women, under the assumption that no compensation takes place. In the 100% sweetener scenario, the average BMI decreased 1.7 kg/m(2) in men and 1.3 kg/m(2) in women when compared to the 100% sugar scenario. Risks are negligible, as the intake of intense sweeteners remains below the ADI in the substitution scenario. CONCLUSIONS: Substitution of added sugar by intense sweeteners in carbonated soft drinks has beneficial effects on BMI and the reduction in dental caries, and does not seem to have adverse health effects in young adults, given the available knowledge and assumptions made.

Assessment of health claims, content, and safety of herbal supplements containing Ginkgo biloba.

BACKGROUND: European Regulation 1924/2006 states that all health claims made on foods need to be substantiated scientifically. OBJECTIVE: To apply the PASSCLAIM criteria for the scientific substantiation of health claims on foods to herbal supplements containing Ginkgo biloba. Evaluation of three selected claimed health effects for G. biloba (improvement of blood circulation, improvement of symptoms of old age, and improvement of memory) was achieved through review of publicly available scientific data. A total of 35 human intervention studies were evaluated. Commercially available products claimed to contain mainly G. biloba (N=29) were randomly sampled in the Netherlands and analyzed for their content on ginkgo extract. Also, a toxicological risk assessment was performed. RESULTS: The three selected health claims investigated could not be substantiated. This was mainly because of a lack of data from studies in healthy volunteers. In most studies results performed with a 24% standardized G. biloba extract were described. However, our chemical analysis showed that 25 of the 29 sampled products did not contain the required minimum 24% standardized extract. Moreover, in most preparations the content of substances typical for G. biloba did not conform to what was declared on the label. Since toxicity data for G. biloba are very limited, a safety limit could not be established. CONCLUSIONS: Evidence is lacking for three health claims of herbal products with G. biloba. Neither safety nor efficacy can be guaranteed at the recommended daily dose. The multidisciplinary approach described in this paper provides good insight into issues that are relevant for the evaluation of health claims for herbal food supplements.

Support of drug therapy using functional foods and dietary supplements: focus on statin therapy.

Functional foods and dietary supplements might have a role in supporting drug therapy. These products may (1) have an additive effect to the effect that a drug has in reducing risk factors associated with certain conditions, (2) contribute to improve risk factors associated with the condition, other than the risk factor that the drug is dealing with, or (3) reduce drug-associated side effects, for example, by restoring depleted compounds or by reducing the necessary dose of the drug. Possible advantages compared with a multidrug therapy are lower drug costs, fewer side effects and increased adherence. In the present review we have focused on the support of statin therapy using functional foods or dietary supplements containing plant sterols and/or stanols, soluble dietary fibre, n-3 PUFA or coenzyme Q10. We conclude that there is substantial evidence that adding plant sterols and/or stanols to statin therapy further reduces total and LDL-cholesterol by roughly 6 and 10 %, respectively. Adding n-3 PUFA to statin therapy leads to a significant reduction in plasma TAG of at least 15 %. Data are insufficient and not conclusive to recommend the use of soluble fibre or coenzyme Q10 in patients on statin therapy and more randomised controlled trials towards these combinations are warranted. Aside from the possible beneficial effects from functional foods or dietary supplements on drug therapy, it is important to examine possible (negative) effects from the combination in the long term, for example, in post-marketing surveillance studies. Moreover, it is important to monitor whether the functional foods and dietary supplements are taken in the recommended amounts to induce significant effects.

Integrated risk-benefit analyses: method development with folic acid as example.

With the introduction of novel and functional foods, there is increasing need for an integrated quantitative risk-benefit assessment of foods. Consensus about a quantitative risk-benefit assessment mirroring the risk assessment approach has been reached during a recent EFSA workshop. In line, we propose a risk-benefit model that consists of: (1) hazard and benefit identification, (2) hazard and benefit characterization through dose-response functions, (3) exposure assessment, and (4) risk-benefit integration. The DALY, which combines morbidity and mortality serves as common health measure. The overall health impact of bread fortified with folic acid in the Netherlands has been simulated. The case study showed how the risk-benefit approach may assist a policy maker in decisions on food fortification programs. It illustrates general problems regarding the data demands, the assumptions and uncertainties. A simple sensitivity analysis showed which assumptions were most crucial. Modest fortification (140 microg/100 g bread) seems reasonable to improve public health but the results hinge on the assumptions one makes for the association between colorectal cancer and high folate intake. A precautious policymaker may very well decide against folic acid fortification. The often debated increase in masked vitamin B(12)-deficiency appears negligible compared to the health gain resulting from prevented neural tube defects.

Safe addition of vitamins and minerals to foods: setting maximum levels for fortification in the Netherlands.

BACKGROUND: In 2004, the European Court of Justice decided that the prohibition of fortification with vitamin A, vitamin D, folic acid, selenium, copper, and zinc in the Netherlands conflicts with the principle of free movement of goods in the European Union. This decision led to a change in the Dutch policy, resulting in a more flexible handling of requests for exemption from this prohibition to fortify. Therefore, an investigation was proposed in which it would be determined whether a general exemption could be granted for food fortification with a certain maximum safe amount per micronutrient. AIM OF THE STUDY: To develop a risk assessment model to estimate maximum safe fortification levels (MSFLs) of vitamins and minerals to foods on the Dutch market, and to evaluate these levels to derive allowed fortification levels (AFLs), which can be used for a general exemption. METHODS: We developed a risk assessment model to estimate MSFLs of vitamins and minerals to foods on the basis of existing models. We used European tolerable upper intake levels in combination with national food consumption data to estimate MSFLs for fortification of foods for several age groups. Upon extensive stakeholder dialogue, the risk manager considered these estimated MSFLs and the final AFLs for a general exemption were set. RESULTS: For folic acid, vitamin A, and vitamin D, the MSFLs were calculated in the risk-assessment model. Children up to 6-years old were the group most sensitive to folic acid fortification, and they had an MSFL of 0 microg/100 kcal, but following a risk management evaluation, this was upgraded to an AFL of 100 microg/100 kcal. The MSFL for vitamin D was 3.0 microg/100 kcal (children 4-10 years old), and the risk manager increased this to an AFL of 4.5 microg/100 kcal. Children up to 10 years old, men, and postmenopausal women were the groups most sensitive to vitamin A fortification (MSFL = 0 microg/100 kcal). Because these groups represent a large part of the population and because of the seriously harmful effects of excessive vitamin A, the risk manager did not allow a general exemption. CONCLUSIONS: The combination of a risk assessment model and risk manager evaluation led to the setting of AFLs for general exemption of fortification with folic acid and vitamin D. This model is also applicable for other micronutrients, for which an UL is derived, and in other countries.