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IntroductionProximity and access to water have long been central to human culture and accordingly deliver countless societal benefits. Over 200 million people live on Europe’s coastline, and aquatic environments are the top recreational destination in the region. In terms of public health, interactions with ‘blue space’ (eg, coasts, rivers, lakes) are often considered solely in terms of risk (eg, drowning, microbial pollution). Exposure to blue space can, however, promote health and well-being and prevent disease, although underlying mechanisms are poorly understood.Aims and methodsThe BlueHealth project aims to understand the relationships between exposure to blue space and health and well-being, to map and quantify the public health impacts of changes to both natural blue spaces and associated urban infrastructure in Europe, and to provide evidence-based information to policymakers on how to maximise health benefits associated with interventions in and around aquatic environments. To achieve these aims, an evidence base will be created through systematic reviews, analyses of secondary data sets and analyses of new data collected through a bespoke international survey and a wide range of community-level interventions. We will also explore how to deliver the benefits associated with blue spaces to those without direct access through the use of virtual reality. Scenarios will be developed that allow the evaluation of health impacts in plausible future societal contexts and changing environments. BlueHealth will develop key inputs into policymaking and land/water-use planning towards more salutogenic and sustainable uses of blue space, particularly in urban areas.Ethics and disseminationThroughout the BlueHealth project, ethics review and approval are obtained for all relevant aspects of the study by the local ethics committees prior to any work being initiated and an ethics expert has been appointed to the project advisory board. So far, ethical approval has been obtained for the BlueHealth International Survey and for community-level interventions taking place in Spain, Italy and the UK. Engagement of stakeholders, including the public, involves citizens in many aspects of the project. Results of all individual studies within the BlueHealth project will be published with open access. After full anonymisation and application of any measures necessary to prevent disclosure, data generated in the project will be deposited into open data repositories of the partner institutions, in line with a formal data management plan. Other knowledge and tools developed in the project will be made available via the project website (www.bluehealth2020.eu). Project results will ultimately provide key inputs to planning and policy relating to blue space, further stimulating the integration of environmental and health considerations into decision-making, such that blue infrastructure is developed across Europe with both public health and the environment in mind.

BackgroundThe current paradigm for the assessment of the health risk of chemical substances focuses primarily on the effects of individual substances for determining the doses of toxicological concern in order to inform appropriately the regulatory process. These policy instruments place varying requirements on health and safety data of chemicals in the environment. REACH focuses on safety of individual substances; yet all the other facets of public health policy that relate to chemical stressors put emphasis on the effects of combined exposure to mixtures of chemical and physical agents. This emphasis brings about methodological problems linked to the complexity of the respective exposure pathways; the effect (more complex than simple additivity) of mixtures (the so-called 'cocktail effect'); dose extrapolation, i.e. the extrapolation of the validity of dose-response data to dose ranges that extend beyond the levels used for the derivation of the original dose-response relationship; the integrated use of toxicity data across species (including human clinical, epidemiological and biomonitoring data); and variation in inter-individual susceptibility associated with both genetic and environmental factors.MethodsIn this paper we give an overview of the main methodologies available today to estimate the human health risk of environmental chemical mixtures, ranging from dose addition to independent action, and from ignoring interactions among the mixture constituents to modelling their biological fate taking into account the biochemical interactions affecting both internal exposure and the toxic potency of the mixture.ResultsWe discuss their applicability, possible options available to policy makers and the difficulties and potential pitfalls in implementing these methodologies in the frame of the currently existing policy framework in the European Union. Finally, we suggest a pragmatic solution for policy/regulatory action that would facilitate the evaluation of the health effects of chemical mixtures in the environment and consumer products.ConclusionsOne universally applicable methodology does not yet exist. Therefore, a pragmatic, tiered approach to regulatory risk assessment of chemical mixtures is suggested, encompassing (a) the use of dose addition to calculate a hazard index that takes into account interactions among mixture components; and (b) the use of the connectivity approach in data-rich situations to integrate mechanistic knowledge at different scales of biological organization.

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In order to identify compounds with potential toxicity problems, particular attention is paid to structural alerts, which are high chemical reactivity molecular fragments or fragments that can be transformed via bioactivation by human enzymes into fragments with high chemical reactivity. The concept has been introduced in order to reduce the likelihood that future candidate substances as pharmaceuticals will have undesirable toxic effects. A significant proportion (∼78–86%) of drugs characterized by residual toxicity contain structural alerts; there is also evidence indicating the formation of active metabolites as a causal factor for the toxicity of 62–69% of these molecules. On the other hand, the pharmacological action of certain drugs depends on the formation of reactive metabolites. Detailed assessment of the potential for the formation of active metabolites is recommended to characterize a biologically active compound. Although many prescribed drugs frequently contain structural alerts and form reactive metabolites, the vast majority of these drugs are administered in low daily doses. Avoiding structural alerts has become almost a norm in new drug design. An in-depth review of the biochemical reactivity of these structural alerts for new drug candidates is critical from a safety point of view and is currently being monitored in the discovery of drugs. The chemical strategies applied to structural alerts in molecules to limit the toxicity are:partial replacement or full replacement of the structural alert;reduction of electronic density;introduction of a structural element of metabolic interest (metabolic switching);multiple approaches.Therefore, chemical intervention strategies to eliminate bioactivation are often interactive processes; their success depends largely on a close working relationship between drug chemists, pharmacologists and researchers in metabolic science.

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The complexity of the human exposome—the totality of environmental exposures encountered from birth to death—motivates systematic, high-throughput approaches to discover new environmental determinants of disease. In this review, we describe the state of science in analyzing the human exposome and provide recommendations for the public health community to consider in dealing with analytic challenges of exposome-based biomedical research. We describe extant and novel analytic methods needed to associate the exposome with critical health outcomes and contextualize the data-centered challenges by drawing parallels to other research endeavors such as human genomics research. We discuss efforts for training scientists who can bridge public health, genomics, and biomedicine in informatics and statistics. If an exposome data ecosystem is brought to fruition, it will likely play a role as central as genomic science has had in molding the current and new generations of biomedical researchers, computational scientists, and public health research programs.