Towards a Swiss health study with human biomonitoring: Learnings from the pilot phase about participation and design.

BACKGROUND: A large-scale national cohort aiming at investigating the health status and determinants in the general population is essential for high-quality public health research and regulatory decision-making. We present the protocol and first results of the pilot phase to a Swiss national cohort aiming at establishing the study procedures, evaluating feasibility, and assessing participation and willingness to participate. METHODS: The pilot phase 2020/21 included 3 components recruited via different channels: a population-based cross-sectional study targeting the adult population (20-69 years) of the Vaud and Bern cantons via personal invitation, a sub-study on selenium in a convenience sample of vegans and vegetarians via non-personal invitation in vegan/vegetarian networks, and a self-selected sample via news promotion (restricted protocol). Along with a participatory approach and participation, we tested the study procedures including online questionnaires, onsite health examination, food intake, physical activity assessments and biosample collection following high-quality standards. RESULTS: The population-based study and the selenium sub-study had 638 (participation rate: 14%) and 109 participants, respectively, both with an over-representation of women. Of altogether 1349 recruited participants over 90% expressed interest in participating to a national health study, over 75% to contribute to medicine progress and help improving others' health, whereas about one third expressed concerns over data protection and data misuse. CONCLUSIONS: Publicly accessible high-quality public health data and human biomonitoring samples were collected. There is high interest of the general population in taking part in a national cohort on health. Challenges reside in achieving a higher participation rate and external validity. For project management clear governance is key.

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.

Application of human biomonitoring data to support policy development, raise awareness and environmental public health protection among countries within the HBM4EU project.

Most countries have acknowledged the importance of assessing and quantifying their population's internal exposure from chemicals in air, water, soil, food and other consumer products due to the potential health and economic impact. Human biomonitoring (HBM) is a valuable tool which can be used to quantify such exposures and effects. Results from HBM studies can also contribute to improving public health by providing evidence of individuals' internal chemical exposure as well as data to understand the burden of disease and associated costs thereby stimulating the development and implementation of evidence-based policy. To have a holistic view on HBM data utilisation, a multi-case research approach was used to explore the use of HBM data to support national chemical regulations, protect public health and raise awareness among countries participating in the HBM4EU project. The Human Biomonitoring for Europe (HBM4EU) Initiative (https://www.hbm4eu.eu/) is a collaborative effort involving 30 countries, the European Environment Agency (EEA) and the European Commission (contracting authority) to harmonise procedures across Europe and advance research into the understanding of the health impacts of environmental chemical exposure. One of the aims of the project was to use HBM data to support evidence based chemical policy and make this information timely and directly available for policy makers and all partners. The main data source for this article was the narratives collected from 27 countries within the HBM4EU project. The countries (self-selection) were grouped into 3 categories in terms of HBM data usage either for public awareness, policy support or for the establishment HBM programme. Narratives were analysed/summarised using guidelines and templates that focused on ministries involved in or advocating for HBM; steps required to engage policy makers; barriers, drivers and opportunities in developing a HBM programme. The narratives reported the use of HBM data either for raising awareness or addressing environmental/public health issues and policy development. The ministries of Health and Environment were reported to be the most prominent entities advocating for HBM, the involvement of several authorities/institutions in the national hubs was also cited to create an avenue to interact, discuss and gain the attention of policy makers. Participating in European projects and the general population interest in HBM studies were seen as drivers and opportunities in developing HBM programmes. A key barrier that was cited by countries for establishing and sustaining national HBM programmes was funding which is mainly due to the high costs associated with the collection and chemical analysis of human samples. Although challenges and barriers still exist, most countries within Europe were already conversant with the benefits and opportunities of HBM. This article offers important insights into factors associated with the utilisation of HBM data for policy support and public awareness.

SCCS Scientific Opinion on Acid Yellow 3 (submission II) - SCCS/1631/21.

Opinion to be cited as: SCCS (Scientific Committee on Consumer Safety), Opinion on Acid Yellow 3 - C054 (CAS Number 8004-92-0, EC No 305-897-5), submission II, preliminary version of 7 May 2021, final version of 23 July 2021, SCCS/1631/21.

SCCS scientific opinion on Butylated hydroxytoluene (BHT) - SCCS/1636/21.

OPINION TO BE CITED AS: SCCS (Scientific Committee on Consumer Safety), scientific opinion on Butylated hydroxytoluene (BHT), preliminary version of September 27, 2021, final version of December 2, 2021, SCCS/1636/21.

The European exposure science strategy 2020-2030.

Exposure science is an emerging and rapidly growing field dedicated to all aspects concerning the contact between chemical, biological, physical or psycho-social stressors and human and ecological receptors. With that, exposure science plays a central role in protecting human and ecosystem health, and contributes to the global transition towards a green and sustainable society. In Europe, however, exposure science is currently not sufficiently recognised as a scientific field, resulting in inefficient uptake into policies. In response, the wider European exposure science community developed elements and actions under the auspices of the Europe Regional Chapter of the International Society of Exposure Science (ISES Europe), for identified priority areas, namely education, exposure models, exposure data, human biomonitoring, and policy uptake. In the present document, we synthesize these strategic elements into an overarching 'European Exposure Science Strategy 2020-2030', following three strategic objectives that focus on acknowledging exposure science as an independent and interconnected field, harmonizing approaches and tools across regulations, and exploring collaboration, education and funding mechanisms. To operationalise this strategy, we present concrete key actions and propose initiatives and funding options for advancing the underlying science, cultivating broader education and cross-sector exposure knowledge transfer, and fostering effective uptake of exposure information into policy. We aim at anchoring European efforts in the global exposure science context, with a special focus on the interface between scientific advancements, application in decision support, and dissemination and training. This will help to develop exposure science as a strong scientific field with the ultimate goal to successfully assess and manage various stressors across sectors and geographic scales.

Framework for developing an exposure science curriculum as part of the European Exposure Science Strategy 2020-2030.

BACKGROUND: Evaluating and managing exposures to chemical, physical and biological stressors, which frequently interplay with psychological stressors as well as social and behavioural aspects, is crucial for protecting human and environmental health and transitioning towards a sustainable future. Advances in our understanding of exposure rely on input from well-trained exposure scientists. However, no education programmes in Europe are currently explicitly dedicated to cover the broader range of exposure science approaches, applications, stressors and receptors. OBJECTIVE: To address this challenge, a curriculum is needed that yields credible, well-defined career pathways in exposure science. METHODS: Needs and conditions for advancing exposure science education in Europe were identified. As a starting point for a way forward, harmonised learning outcomes for exposure science were defined at each level of the European Qualifications Framework. The course programme coordinators were recruited for three varying courses, with respect to the course level and the proportion of the curriculum dedicated to exposure science. These courses were assessed via our systematic course review procedure. Finally, strategic objectives and actions are proposed to build exposure science education programmes. RESULTS: The ISES Europe 'Education, Training and Communication' expert working group developed a framework for creating a viable exposure science curriculum. Harmonised learning outcomes were structured under eight learning levels, categorised by knowledge, skills and competence. Illustrative case studies demonstrated how education providers integrated these learning outcomes for their educational context and aligned the overall exposure science curriculum. CONCLUSIONS: The international recognition and adoption of exposure science education will enable advances in addressing global exposure science challenges for various stressors, from behavioural aspects from individual to population scale, and effective communication between exposure scientists and relevant stakeholders and policy makers, as part of the European Exposure Science Strategy 2020-2030.

Exposure modelling in Europe: how to pave the road for the future as part of the European Exposure Science Strategy 2020-2030.

Exposure models are essential in almost all relevant contexts for exposure science. To address the numerous challenges and gaps that exist, exposure modelling is one of the priority areas of the European Exposure Science Strategy developed by the European Chapter of the International Society of Exposure Science (ISES Europe). A strategy was developed for the priority area of exposure modelling in Europe with four strategic objectives. These objectives are (1) improvement of models and tools, (2) development of new methodologies and support for understudied fields, (3) improvement of model use and (4) regulatory needs for modelling. In a bottom-up approach, exposure modellers from different European countries and institutions who are active in the fields of occupational, population and environmental exposure science pooled their expertise under the umbrella of the ISES Europe Working Group on exposure models. This working group assessed the state-of-the-art of exposure modelling in Europe by developing an inventory of exposure models used in Europe and reviewing the existing literature on pitfalls for exposure modelling, in order to identify crucial modelling-related strategy elements. Decisive actions were defined for ISES Europe stakeholders, including collecting available models and accompanying information in a living document curated and published by ISES Europe, as well as a long-term goal of developing a best-practices handbook. Alongside these actions, recommendations were developed and addressed to stakeholders outside of ISES Europe. Four strategic objectives were identified with an associated action plan and roadmap for the implementation of the European Exposure Science Strategy for exposure modelling. This strategic plan will foster a common understanding of modelling-related methodology, terminology and future research in Europe, and have a broader impact on strategic considerations globally.

Theoretical Background of Occupational-Exposure Models-Report of an Expert Workshop of the ISES Europe Working Group "Exposure Models".

On 20 October 2020, the Working Group "Exposure Models" of the Europe Regional Chapter of the International Society of Exposure Science (ISES Europe) organised an online workshop to discuss the theoretical background of models for the assessment of occupational exposure to chemicals. In this report, participants of the workshop with an active role before and during the workshop summarise the most relevant discussion points and conclusions of this well-attended workshop. ISES Europe has identified exposure modelling as one priority area for the strategic development of exposure science in Europe in the coming years. This specific workshop aimed to discuss the main challenges in developing, validating, and using occupational-exposure models for regulatory purposes. The theoretical background, application domain, and limitations of different modelling approaches were presented and discussed, focusing on empirical "modifying-factor" or "mass-balance-based" approaches. During the discussions, these approaches were compared and analysed. Possibilities to address the discussed challenges could be a validation study involving alternative modelling approaches. The wider discussion touched upon the close relationship between modelling and monitoring and the need for better linkage of the methods and the need for common monitoring databases that include data on model parameters.

A human biomonitoring (HBM) Global Registry Framework: Further advancement of HBM research following the FAIR principles.

Data generated by the rapidly evolving human biomonitoring (HBM) programmes are providing invaluable opportunities to support and advance regulatory risk assessment and management of chemicals in occupational and environmental health domains. However, heterogeneity across studies, in terms of design, terminology, biomarker nomenclature, and data formats, limits our capacity to compare and integrate data sets retrospectively (reuse). Registration of HBM studies is common for clinical trials; however, the study designs and resulting data collections cannot be traced easily. We argue that an HBM Global Registry Framework (HBM GRF) could be the solution to several of challenges hampering the (re)use of HBM (meta)data. The aim is to develop a global, host-independent HBM registry framework based on the use of harmonised open-access protocol templates from designing, undertaking of an HBM study to the use and possible reuse of the resulting HBM (meta)data. This framework should apply FAIR (Findable, Accessible, Interoperable and Reusable) principles as a core data management strategy to enable the (re)use of HBM (meta)data to its full potential through the data value chain. Moreover, we believe that implementation of FAIR principles is a fundamental enabler for digital transformation within environmental health. The HBM GRF would encompass internationally harmonised and agreed open access templates for HBM study protocols, structured web-based functionalities to deposit, find, and access harmonised protocols of HBM studies. Registration of HBM studies using the HBM GRF is anticipated to increase FAIRness of the resulting (meta)data. It is also considered that harmonisation of existing data sets could be performed retrospectively. As a consequence, data wrangling activities to make data ready for analysis will be minimised. In addition, this framework would enable the HBM (inter)national community to trace new HBM studies already in the planning phase and their results once finalised. The HBM GRF could also serve as a platform enhancing communication between scientists, risk assessors, and risk managers/policy makers. The planned European Partnership for the Assessment of Risk from Chemicals (PARC) work along these lines, based on the experience obtained in previous joint European initiatives. Therefore, PARC could very well bring a first demonstration of first essential functionalities within the development of the HBM GRF.

The SCCS scientific advice on the safety of nanomaterials in cosmetics.

The Cosmetic Regulation (EC) No 1223/2009 specifically covers the risk of nanomaterials used in cosmetic products. If there are concerns regarding the safety of a nanomaterial, the European Commission refers it to the SCCS for a scientific opinion. The Commission mandated the SCCS to identify the scientific basis for safety concerns that could be used as a basis for identifying and prioritising nanomaterials for safety assessment, and to revisit previous inconclusive SCCS opinions on nanomaterials to identify any concerns for potential risks to the consumer health. The SCCS Scientific Advice identified the key general aspects of nanomaterials that should raise a safety concern for a safety assessor/manager, so that the nanomaterial(s) in question could be subjected to safety assessment to establish safety to the consumer. The Advice also developed a list of the nanomaterials notified to the Commission for use in cosmetics in an order of priority for safety assessment, and revisited three previous inconclusive opinions on nanomaterials to highlight concerns over consumer safety that merited further safety assessment.

Assessing Human Exposure to SVOCs in Materials, Products, and Articles: A Modular Mechanistic Framework.

A critical review of the current state of knowledge of chemical emissions from indoor sources, partitioning among indoor compartments, and the ensuing indoor exposure leads to a proposal for a modular mechanistic framework for predicting human exposure to semivolatile organic compounds (SVOCs). Mechanistically consistent source emission categories include solid, soft, frequent contact, applied, sprayed, and high temperature sources. Environmental compartments are the gas phase, airborne particles, settled dust, indoor surfaces, and clothing. Identified research needs are the development of dynamic emission models for several of the source emission categories and of estimation strategies for critical model parameters. The modular structure of the framework facilitates subsequent inclusion of new knowledge, other chemical classes of indoor pollutants, and additional mechanistic processes relevant to human exposure indoors. The framework may serve as the foundation for developing an open-source community model to better support collaborative research and improve access for application by stakeholders. Combining exposure estimates derived using this framework with toxicity data for different end points and toxicokinetic mechanisms will accelerate chemical risk prioritization, advance effective chemical management decisions, and protect public health.

Analysis of consumer behavior for the estimation of the exposure to chemicals in personal care products.

In this study, the main objective was to implement an integrative modelling framework in order to support the prioritization and screening of chemicals present in personal care products (PCPs) regarding their potential to expose users across multiple possible pathways. Here, we implemented an exposure-based framework based on product intake fractions (PiFs) calculated using a two-compartment model reproducing the skin uptake and the competing volatilization of chemicals applied on skin during PCP use. The implemented framework enabled to simultaneously and comprehensively accommodate coupled chemical specific parameters (i.e. physical and chemical properties of the candidate chemicals), exposure information specific for product-chemical combinations, and survey data informing on consumer behavior. A case-study, based on the usage pattern data of 22 PCPs investigated among Swiss individuals (Garcia-Hidalgo et al., 2017a) and 113 candidate chemicals chosen for their suspected presence in the PCP categories of interest was defined to evaluate the applicability of the framework. Nonnegative matrix factorization (NMF) and hierarchical clustering were subsequently applied to identify chemicals with the highest exposure potential and to highlight most relevant mixtures of chemicals on the basis of the specific usage patterns of the considered survey individuals.

The way forward for assessing the human health safety of cosmetics in the EU - Workshop proceedings.

Although the need for non-animal alternatives has been well recognised for the human health hazard assessment of chemicals in general, it has become especially pressing for cosmetic ingredients due to the full implementation of testing and marketing bans on animal testing under the European Cosmetics Regulation. This means that for the safety assessment of cosmetics, the necessary safety data for both the ingredients and the finished product can be drawn from validated (or scientifically-valid), so-called "Replacement methods". In view of the challenges for safety assessment without recourse to animal test data, the Methodology Working Group of the Scientific Committee on Consumer Safety organised a workshop in February 2019 to discuss the key issues in regard to the use of animal-free alternative methods for the safety evaluation of cosmetic ingredients. This perspective article summarises the outcomes of this workshop and reflects on the state-of-the-art and possible way forward for the safety assessment of cosmetic ingredients for which no experimental animal data exist. The use and optimisation of "New Approach Methodology" that could be useful tools in the context of the "Next Generation Risk Assessment" and the strategic framework for safety assessment of cosmetics were discussed in depth.

Estimating polybrominated diphenyl ether (PBDE) exposure through seafood consumption in Switzerland using international food trade data.

Seafood is a major source of human exposure to polybrominated diphenyl ethers (PBDEs). The intake of these globally distributed and bioaccumulative contaminants depends on both consumption patterns (which seafoods are consumed) and on their origins. Here, we investigate exposure to PBDEs through seafood consumption as a function of species, origins and consumption levels. We estimate the contribution of seafood consumption to PBDE exposures in the Swiss population using two approaches. The first approach estimates exposures by estimating the composition of the Swiss seafood diet using trade data and national statistics on total seafood consumption. This naïve approach could be used for any country for which no individually reported consumption data are available for a population. The second approach uses dietary survey data provided by the Swiss Federal Statistical Office as part of the menuCH study for exposure estimates. To support region- and species-specific estimates of exposures for both approaches, we built a database of PBDE concentrations in seafood by analysis of published PBDE levels in fish from food markets or freshwater resources from various countries. We find estimated PBDE exposures ranging from 0.15 to 0.65 ng/kg bw/day for the trade data-based diet. These were close to the median exposures of 0.68 ng/kg bw/day for the Swiss population based on the menuCH survey, indicating that the composition and consumption rate derived from trade data are appropriate for calculating exposures in the average adult population. However, it could not account for PBDE exposures of more vulnerable (high seafood consuming) populations captured only by the survey data. All estimates were lower than the PBDE Chronic Oral Reference Doses (RfD's) suggested by the EPA, but could increase substantially to a value of 7 ng/kg bw/day if fish are sourced from the most contaminated origins, as in the case of Vietnamese shrimp/prawn, Norwegian salmon, and Swiss whitefish. Exposures as high as 8.50 ng/kg bw/day are estimated for the survey-based diet, which better captures the variability in consumption by individuals, including extreme high and low values. In general, the most frequently consumed species reported by Swiss consumers are consistent with those predicted using trade data.

The EuroMix human biomonitoring study: Source-to-dose modeling of cumulative and aggregate exposure for the bisphenols BPA, BPS, and BPF and comparison with measured urinary levels.

BACKGROUND: Bisphenol A (BPA) and, with increasing occurrence, its analogs bisphenol S (BPS) and bisphenol F (BPF) are applied in many consumer products, leading to humans being exposed from a vast number of sources and via several routes. Estrogenic and anti-androgenic effects are exerted by the chemical BPA, and also by its analogs. Therefore, realistic exposure assessments are needed for assessing risks related to cumulative exposure. OBJECTIVES: Biomonitoring for BPA, BPS, and BPF was conducted in a human study embedded in the EU project EuroMix and the measured urinary concentrations were compared to source-to-dose calculations for source allocation and plausibility test of the model. METHODS: For two 24-hour study periods separated by 2-3 weeks, 144 adult volunteers in Norway kept detailed diaries on food consumption, personal care product (PCP) use, and thermal paper (TP) handling. Concurrently, 24 h urine was collected and urinary levels of BPA, BPS, and BPF were analyzed using ultra-high performance liquid chromatography and tandem mass spectrometry (UPLC-MS-MS). In line with the information obtained from the first study day, bisphenol exposure from food, PCPs, TP, and dust was modeled primarily individual-based with probabilistic models. Estimates for BP excretion over 24 h were obtained with the models and compared to measured amounts. RESULTS: Modeled aggregate internal exposures covered the full range of measured urinary amounts for all BP analogs. In general, individual-based medians of modeled BPA exposures were in good agreement with the measurements, but individual-specific correlation was lacking. Modeled exposures mostly underestimated BPS and BPF levels in participants with positive measurements (53% and 8%), except for the P95 values of modeled BPS exposure that were higher than measured amounts if TP was handled. Most likely, diet and TP were the sources contributing the most to BP exposure in this study. Urinary measurements did not reveal a significant correlation between the amounts of canned food consumed, the number of PCPs used, or the number of TP handling events and levels of BPA, BPS, or BPF. CONCLUSIONS: The good agreement between the ranges of modeled BPA exposure and measured BPA amounts indicates that available concentrations, especially from the main exposure source food, mirror the exposure situation realistically, and suggests that the exposure model considers the relevant exposure sources. The lack of individual-specific correlations means that the individual measured amounts and modeled exposures did not vary in parallel, e.g. due to mismatch of BP concentrations in food, TP, and other sources, or delayed internal exposure. The underestimation of modeled BPS and BPF exposure suggests that not all relevant sources were included in the respective exposure models. This could be due to a lack of input data, e.g. for food items, or due to an increased replacement of BPA with structural analogs compared to the used concentration and occurrence data.

Building a European exposure science strategy.

Exposure information is a critical element in various regulatory and non-regulatory frameworks in Europe and elsewhere. Exposure science supports to ensure safe environments, reduce human health risks, and foster a sustainable future. However, increasing diversity in regulations and the lack of a professional identity as exposure scientists currently hamper developing the field and uptake into European policy. In response, we discuss trends, and identify three key needs for advancing and harmonizing exposure science and its application in Europe. We provide overarching building blocks and define six long-term activities to address the identified key needs, and to iteratively improve guidelines, tools, data, and education. More specifically, we propose creating European networks to maximize synergies with adjacent fields and identify funding opportunities, building common exposure assessment approaches across regulations, providing tiered education and training programmes, developing an aligned and integrated exposure assessment framework, offering best practices guidance, and launching an exposure information exchange platform. Dedicated working groups will further specify these activities in a consistent action plan. Together, these elements form the foundation for establishing goals and an action roadmap for successfully developing and implementing a 'European Exposure Science Strategy' 2020-2030, which is aligned with advances in science and technology.