Management of Emerging Public Health Issues and Risks: Multidisciplinary Approaches to the Changing Environment

Management of Emerging Public Health Issues and Risks: Multidisciplinary Approaches to the Changing Environment addresses the threats facing the rapidly changing world and provides guidance on how to manage risks to population health. Unlike conventional and recognized risks (major, industrial, and natural), emerging risks are characterized by low or non-existent scientific knowledge, high levels of uncertainty, and different levels of acceptability by the relevant authorities and exposed populations. Emerging risk must be analyzed through multiple and crossed approaches identifying the phenomenon linked to the emergence of risk but also by combining scientific, policy and social data in order to provide more enlightened decision making. Management of Emerging Public Health Issues and Risks: Multidisciplinary Approaches to the Changing Environment provides examples of transdisciplinary approaches used to characterize, analyze, and manage emerging risks. This book will be useful for public health researchers, policy makers, and students as well as those working in emergency management, risk management, security, environmental health, nanomaterials, and food science.

• Presents emerging risks from the technological, environmental, health, and energy sectors, as well as their social impacts
• Contextualizes emerging risks as new threats, existing threats in new locations, and known issues, which are newly recognized as risks due to increased scientific knowledge
• Includes case studies from around the world to reinforce concepts

• Language: English
• Publisher: Academic Press
• Release date: Nov 13, 2018
• ISBN: 9780128132913

Book preview

Management of Emerging Public Health Issues and Risks

Multidisciplinary Approaches to the Changing Environment

Editors

Benoit Roig

University of Nîmes, EA7352 CHROME, Nîmes, France

Karine Weiss

University of Nîmes, EA7352 CHROME, Nîmes, France

Véronique Thireau

University of Nîmes, EA7352 CHROME, Nîmes, France

Table of Contents

Cover image

Title page

Copyright

List of Contributors

Preface

Introduction: Needs on Emerging Risk and Management

The Exposome: A New Tool for Improved Health Risk Assessment

Part 1. New Risks

Chapter 1. Indoor Air and Public Health

1. Introduction

2. Indoor Settings

3. Coexposure to Indoor Air Pollutants

4. Impacts of Coexposure to Indoor Air Pollutants

5. Health Risk Modifiers

6. Conclusions

Chapter 2. Advanced Manufacturing Processes and Technologies

1. Introduction

2. Emerging Risk Concept

3. Overview of Advanced Manufacturing Processes and Technologies

4. Emerging Risks Linked With Advanced Manufacturing Processes and Technologies

5. Risk Governance

6. Conclusions

Chapter 3. Multidimensional Impacts of Nanotechnology on Public Health

1. Introduction

2. Nano Overview

3. Nano and the Workplace

4. Nano in Consumer Products

5. Nano in the Environment

6. Applications of Nanotechnology in the Service of Public Health

7. Nano and Public Health—Looking Back, Looking Ahead

8. Summary and Conclusions

Part 2. Known Risks in New Locations

Chapter 4. The Emergence of Vector-Borne Diseases in New Locations

1. Introduction

2. Changes

3. Vectors and Pathogens

4. One Health Approach and Perspective

Chapter 5. Radioactive Remains

1. Introduction

2. An Unidentified Object Combining Death and Radioactivity

3. Cautious Management

4. Conclusion

Chapter 6. Human Spaces and Nonhuman Species: Social Representations of the Risk of Invasion

1. The Perception of Biological Invasions: A Matter of Sociability

2. What Is Meant by Social Representations?

3. A Building Space of the Acting Knowledge

4. The Jellyfish Invasion

5. The Proliferation of Knotweeds

6. General Discussion

Part 3. Known Issues Now Recognized as Risks Due to an Increase in Scientific Knowledge and/or a Change in the Perception of the Population

Chapter 7. Antimicrobial Resistant Genes and Organisms as Environmental Contaminants of Emerging Concern: Addressing Global Public Health Risks

1. Introduction

2. Environmental Antimicrobial Resistance

3. Risk Assessment and Surveillance of Environmental Antimicrobial Resistance

4. Incorporating Antimicrobial Resistance Into Existing Policy, Regulations, Action Plans, and Global Partnerships

5. Conclusion

Chapter 8. Risk Perception of Pharmaceutical Residues in the Aquatic Environment and Precautionary Measures

1. Introduction

2. Results on Risk Perception

3. Measures: Training for the Medical and Pharmaceutical Sector

4. Conclusions

Chapter 9. Chemistry and Psychology: Cross Views on Pesticide Risks

1. Introduction

2. Pesticides From a Psychosocial Point of View

3. Methodology

4. Results

5. Discussion

6. Conclusion

Chapter 10. Assessment and Management of Risks Associated With Antibiotic Resistance in the Environment

1. Introduction

2. Risks Associated With Dissemination of Resistant Bacteria

3. Risks for Acquisition of Resistance

4. Quantifiable Risks Associated With Antibiotic Resistance

5. Management of Rare and Uncertain Risks

6. Risk Ranking

7. Future Directions and Further Research Areas

Index

Copyright

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List of Contributors

Johan Bengtsson-Palme

Centre for Antibiotic Resistance research (CARe) at University of Gothenburg, Gothenburg, Sweden

Department of Infectious Diseases, Institute of Biomedicine, The Sahlgrenska Academy, University of Gothenburg, Gothenburg, Sweden

Wisconsin Institute for Discovery, University of Wisconsin–Madison, Madison, WI, United States

Francisco Brocal,     Department of Physics, Systems Engineering and Sign Theory, Universidad de Alicante, Alicante, Spain

R. Stephen Brown

School of Environmental Studies, Queen's University, Kingston, ON, Canada

Department of Chemistry, Queen's University, Kingston, ON, Canada

Audrey Courtier,     University of Nîmes, EA7352 CHROME, Nîmes, France

Margot De Battista,     University of Nîmes, EA7352 CHROME, Nîmes, France

Cristina González,     Department of Manufacturing Engineering, Universidad Nacional de Educación a Distancia (UNED), Madrid, Spain

Alberto Gotti,     Environmental Health Engineering, Institute for Advanced Study (IUSS), Pavia, Italy

Konrad Götz,     Institute for Social-Ecological Research (ISOE) GmbH, Frankfurt am Main, Germany

Patricia Hania,     Department of Law and Business Management, Ted Rogers School of Management, Ryerson University, Toronto, ON, Canada

Matthew S. Hull

NanoEarth – An NSF National Center for Earth & Environmental Nanotechnology Infrastructure at Virginia Tech, Blacksburg, VA, United States

NanoSafe, Inc., Blacksburg, VA, United States

Laura Jaeger,     University of Nîmes, EA7352 CHROME, Nîmes, France

Myriam Janin,     University of Nîmes, EA7352 CHROME, Nîmes, France

Spyros P. Karakitsios,     HERACLES Research Center on the Exposome and Health, Center for Interdisciplinary Research and Innovation, Aristotle University of Thessaloniki, Thessaloniki, Greece

Steven N. Liss

School of Environmental Studies, Queen's University, Kingston, ON, Canada

Department of Chemistry and Biology, Ryerson University, Toronto, ON, Canada

Anna Majury

School of Environmental Studies, Queen's University, Kingston, ON, Canada

Public Health Ontario, Kingston, ON, Canada

Tim A. McAllister,     Lethbridge Research and Development Centre, Agriculture and Agri-Food Canada, Lethbridge, AB, Canada

Julien Michon,     University of Nîmes, EA7352 CHROME, Nîmes, France

Tamas Petrovic,     Scientific Veterinary Institute Novi Sad, Serbia

Aleksandar Potkonjak,     Department of Veterinary Medicine, Faculty of Agriculture, University of Novi Sad, Serbia

Patrick Rateau,     University of Nîmes, EA7352 CHROME, Nîmes, France

Benoit Roig,     University of Nîmes, EA7352 CHROME, Nîmes, France

Haley Sanderson,     School of Environmental Studies, Queen's University, Kingston, ON, Canada

Denis A. Sarigiannis

HERACLES Research Center on the Exposome and Health, Center for Interdisciplinary Research and Innovation, Aristotle University of Thessaloniki, Thessaloniki, Greece

Environmental Health Engineering, Institute for Advanced Study (IUSS), Pavia, Italy

Sara Savic,     Scientific Veterinary Institute Novi Sad, Serbia

Miguel A. Sebastián,     Department of Manufacturing Engineering, Universidad Nacional de Educación a Distancia (UNED), Madrid, Spain

Melina Stein,     Institute for Social-Ecological Research (ISOE) GmbH, Frankfurt am Main, Germany

Linda Strelau,     Institute for Social-Ecological Research (ISOE) GmbH, Frankfurt am Main, Germany

Georg Sunderer,     Institute for Social-Ecological Research (ISOE) GmbH, Frankfurt am Main, Germany

Isabelle Techer,     University of Nîmes, EA7352 CHROME, Nîmes, France

Véronique Thireau,     University of Nîmes, EA7352 CHROME, Nîmes, France

Armance Valette,     University of Nîmes, EA7352 CHROME, Nîmes, France

Rodrigo Vidaurre,     Ecologic Institut, Berlin, Germany

Karine Weiss,     University of Nîmes, EA7352 CHROME, Nîmes, France

Martina Winker,     Institute for Social-Ecological Research (ISOE) GmbH, Frankfurt am Main, Germany

Marina Zekic-Stosic,     Scientific Veterinary Institute Novi Sad, Serbia

Preface

The inspiration for this book started after the CHROME research team at the University of Nîmes was accredited. CHROME is interested in the characterization and management of emerging risks. These risks are characterized by uncertainties about their phenomenon, their impact, their consequences, etc. leading to difficulties for effective and confident decision making (particularly in terms of management).

To enable more informed decision making, CHROME proposes cross-approaches, which consist of studying risks by pooling together data from different points of view (both science and technical [exposure, hazard, toxicity, etc.) and humanities [risk perception and representation, economy, policy making, etc.]) and offering a more holistic overview of an unsafe condition. The combination of the data strengthens the decision makers' ability to provide a sound decision of the considered at-risk situation. Developing a risk science means, of course, knowing, identifying, and quantifying the consequences of feared events, but to be satisfied with this diagnosis would be to refuse to see the whole chain of environmental and societal values associated with it, the study of which is just as fundamental for explaining decisions in risk management.

Thanks to this book, we wish to highlight the interest of trans-, inter-, and pluridisciplinary works, particularly in the management of complex concerns. Such approaches are currently in demand, sought, and hoped for. However, they remain poorly developed and little recognized, particularly for funding opportunities. Yet, they represent a credible solution for objective decision making, without a priori knowledge, and not subject to lobbying or other media/political pressures. More than ever, co-construction and co-elaboration by disciplinary mixing must be promoted, valued, and recognized.

We would like to thank all the authors and coauthors without whom this book would not have been possible. They have shown that open-mindedness and the will to break down scientific disciplinary barriers allow high-quality production. We would also like to thank Jennifer Horigan, editor project manager at Elsevier, for her skillful assistance and support in the publishing of this book. Finally, we would like to thank our University of Nîmes for its unconditional support in the development of this original and promising research theme.

Benoit Roig,     Professor in Risk Sciences University of Nîmes, EA7352 CHROME Nîmes, France

Véronique Thireau,     Professor in Economy University of Nîmes, EA7352 CHROME Nîmes, France

Karine Weiss,     Professor in Social Psychology University of Nîmes, EA7352 CHROME Nîmes, France

Introduction: Needs on Emerging Risk and Management

Benoit Roig¹, and Francisco Brocal²,     ¹University of Nîmes, EA7352 CHROME, Nîmes, France,     ²Department of Physics, Systems Engineering and Sign Theory, Universidad de Alicante, Alicante, Spain

The intensity of scientific and technological development is changing society and its relationship with the environment (domestic, professional, environmental, etc.). These modifications generate new opportunities, but also new threats for human health, safety, economy, the environment, and the social structure.

Therefore, society is increasingly concerned about the risks related to these changes, especially about new or increasing risks called emerging risks.

This problematic leads to society’s greater awareness concerning these risks that are associated with many agents and factors derived from their relation to the environment and whose effects may affect the welfare (physical or psychosocial) of the population today and for generations to come.

For several years now, emerging risks have been a subject of high interest, generating studies, and have been a source of debate in the scientific community, in the general population, and by authorities (health, labor, environmental, etc.).

The very concept of emerging risk is also a subject of research and debate. Various definitions exist depending on the nature of the risk (Table 1) or the field of study (systemic, technological, occupational, etc.).

Table 1

These definitions are interrelated but do not completely overlap. However, they all take into account the new and changing nature of the emerging risk. These various definitions recognize that:

• the risk did not exist before: e.g., new technologies (Internet of Things, artificial intelligence, etc.) new materials (nanomaterials, composite materials, etc.), or

• a known risk occurs in a new area: e.g., vector-borne diseases (malaria, dengue, etc.) exported from North Africa to Mediterranean countries (south of France), implementation of an industrial activity in a new area, or

• a problem already long recognized is now considered as risk due to the evolution of the public's perception, or to an increase of the scientific knowledge, e.g., pharmaceutical and personal care products in the environment and their impact on wildlife and human health.

Unlike conventional and recognized risks (major, occupational, natural, etc.), the new and changing nature of the emerging risk implies a low (or nonexistent) scientific knowledge, high uncertainties in their (mode of) assessment, a high characterization difficulty in the scientific field, and a varying level of acceptability by the competent authorities and the populations exposed.

New technologies, nanoparticles, emerging micropollutants (pharmaceuticals products, endocrine disruptors, etc.), climate change, nuclear waste, etc., are examples of emerging issues of which the limits of our knowledge coupled with the methodological difficulties of assessment do not allow to legislate their use or to state the level of risk to the populations. For several of these emerging risks, the scientific debate is only starting. No consensus allows us, firstly, to suggest a regulation, and secondly, to give an objective overview to the population. What is problematic becomes increasingly complex due to a double pressure: the population, who wants to be clearly informed of the legislation and helped in its decision-making; and the media, who want to produce sensational information by using terms taken out of context, not representative of reality and often contradictory.

Therefore, the traditional and disciplinary approaches to study risk (experimental, engineering and technological sciences, management sciences, human and social sciences, etc.) fail when emerging issues need to be investigated. Indeed, although such strategy may be appropriate when problems have simple causes and clearly defined solutions, it is not adapted when the complexity of particular problems is assessed with limited knowledge and relative certainties. In that case, it is important to break the boundaries between the understanding of the risk (risk sources, causes, consequences, etc.), and the social, political, and economic system that determines the ways to reduce or at least limit the impact. Indeed, for the population, an incorrect risk assessment or interpretation can lead to denial, unrealistic optimism, illusions of invulnerability and control, delegation of responsibilities, or to a phenomenon of social amplification of risk. In all of these cases, the behaviors adopted by individuals or communities will be inadequate and will increase in vulnerability. Such lack of clarity and precision about these risks (and the consequences expected) may also be the source of growing disputes (litigation, conflict, jurisprudence, etc.), and of unreasonable behaviors that are sometimes irrational or even dangerous, including in decision-making.

Emerging risks cannot be characterized without crossed approaches (human and social sciences and technological sciences) analyzing and managing the phenomenon linked to their occurrence and their consideration on the scientific level or in the public, the media, and in political decision-making. They need to be studied by combining the different approaches in order to provide more enlightened decision-making.

This book aims to present examples of transdisciplinary approaches used to characterize, analyze, and manage a specific risky situation, considered as emerging. In the framework of environmental health, risk assessment has greatly evolved in the last few decades. One of these new concepts is the concept of exposome, born in 2005. The idea behind this concept is that factors contributing to human diseases are not only genetic and environmental. Other parameters are important as well, including lifestyle, economic or social factors existing from the prenatal period. The concept has rapidly grown in popularity, even if it still raises many interpretations and needs to be more detailed. In a preliminary chapter, Sarigiannis et al. present the concept, some international initiatives and projects, and several applications.

In the following chapters, examples of three categories of emergence are provided. The first chapter presents articles dealing with new risks. In chapter 1, Sarigiannis et al. analyze the current data of a multiple exposure to health risks in the specific context of built environments. Built environments can be contaminated via various sources: traffic proximity (PM, NO2), combustion sources such as biomass for space heating (PM, PAHs), smoke (PM, PAHs, VOCs, carbonyls), building materials (VOCs), furnishings (carbonyls and phthalates), and household products (phthalates, flame retardants, PCBs, and pesticides). The cumulative effect of these substances is not studied enough, whereas people are constantly exposed to them.

In chapter 2, Brocal et al. discuss how the constant progress of new technologies and new manufacturing processes generates the emergence of new risks, both systemic and occupational nature. In a first step, the main emerging risks are exposed. Amongst the fields of application of these risks, some of the most important cross-cutting manufacturing technologies have been selected. In a second step, the chapter presents one of the main frameworks of risks governance and illustrates it through the management and characterization of emerging risks.

Finally, in the third chapter of this first part, Matt Hull addresses the problematics of nanotechnology and public health. Nanotechnologies have rapidly evolved in many fields (nanomaterials, medicines, diagnostic tools, etc.). The benefits of these technological advances are undisputable but the risks of their applications are real. The complexity of nanotechnology is a dual matter: on the one hand, it has opened up new perspectives regarding human welfare, such as progress in the energy sector, in electronic products, in the field of medicine; and on the other hand, unexpected effects of nanoproducts on the environment (emissions to air, water, and soil) and public health (interactions with body tissues, cells, etc.) are described. The chapter provides an overview on the many ways that nanotechnology may impact public health both positively and negatively, showing that more than ever, the benefit/risk ratio needs to be very objectively and conscientiously studied.

The second series of emerging risk described in this book concerns risks already identified (sometimes well characterized) but occurring in new areas. In particular, this is the case with vector-borne diseases. Indeed, vector-borne diseases have been present at man's side for a long time. They are mostly widespread in tropical and subtropical regions, in particular, when there is no access to safe drinking water and health systems. But climate change or global travel can impact the transmission process, in particular in countries where those diseases were previously unknown. The risks that arise during the emergence of vector-borne diseases in new areas can concern human, animal, and environmental health. In chapter 4, Savic et al. discuss the progress in the diagnostic research and examples of vectors and pathogens distributed in new areas. As vector-borne diseases are a matter of public health, it is important to understand, analyze, assess, and manage the risk associated with them.

The second article of this part deals with radioactivity as an emerging risk. In an unconventional way, crossing psychological, chemical, economic, and legal points of view, Jaeger et al. provides in chapter 5 a comprehensive overview on the management of radioactive remains (essentially, the management of low radioactive emissions). Whereas a nuclear plant accident is a high concern for the world's population, much less attention is paid today to permanent exposure to low doses of radioactive elements. However, this risk exists in both the medical and industrial fields and needs to be considered with care.

In the last chapter of this part (chapter 6), Patrick Rateau et al. present the biological invasions related to the spread of some species outside their natural habitats due to climate change. These invasions concern plants as well as animals. This issue is characterized by a scientific uncertainty that leads to various conclusions and to differentiated management choices. In this context of scientific uncertainty, perceptions are highly dissimilar. Therefore, individuals concerned by the problem will not react depending on the reality described by biologists, but rather according to their perceptions of the spread and on the representation that they have of the species. The objective of this chapter is to illustrate this process from two examples: the spread of jellyfish in the Mediterranean area, and the colonization of knotweeds (Fallopia) in the Rhône department and the Gard department of France.

Finally, the last part of the book returns to the subject of recognized situations recently considered as risks due to media or political interests or by new scientific knowledge.

Today, one of the main growing threats to the environment and human health is antimicrobial resistance. This problem is a major concern, with the environment now recognized for its role in the dissemination of resistant bacteria or as a source of new types of resistance to pathogens. This concern is even more serious since therapeutic alternatives are increasingly absent (research on new generations of antibiotics is very low). In two complementary chapters (7 and 10), Sanderson et al. and Bengtsson-Palme discuss the current research related to antimicrobial resistance in the environment (AMR) and the issues related to risk assessment and surveillance, and the incorporation of AMR, which is problematic, into legal frameworks and regulations, public health action plans, and global partnerships that aim to fight against AMR.

Another subject of recent interest is the presence of pharmaceutical products in the environment. Data have shown the likelihood of finding such substances in drinking water and food products (vegetables or seafood products, for instance). Despite the lack of certainties about the risks for human health, there is an effective motivation to find solutions to moderate the emissions of these substances into the environment. In parallel to technical and end-of-pipe options (water treatment), upstream options can be suggested by involving the different actors of the life cycle of pharmaceutical products. In chapter 8, Goetz et al. focus on consumers' and health experts' perceptions of risks caused by pharmaceutical residues in the marine environment. The aim of this study is to make doctors and pharmacists aware of this issue and to qualify them for the measures to be taken in their daily professional life.

Chapter 9 focuses on pesticides. Although pesticides are no longer emerging subjects, new questions are raised due to the use of contaminated water for plant production (irrigation). This matter is one of the bases for the conversion to organic farming, although the toxicity of pesticides on nontarget organisms is becoming increasingly low. In this chapter, Valette et al. try to understand what motivates the conversion, or the nonconversion, to more respectful agricultural practices.

The development of the three parts of this book just described follows the common thread connected to the different definitions of emerging risk due to its new and changing nature. In this way, the first part deals mainly with the new nature of the emerging risk and the second and third parts with the changing nature of the emerging risk, considering new areas and the increase of scientific knowledge and/or changes in the population's perceptions.

With this common thread, the complex connections that occur in a world where globalization and technological development increase exponentially in an interrelated way are shown. This scenario is strongly linked to the life cycle of new products, processes, and activities, which generate emerging risks linked to knowledge of great relevance in the field of public health.

Finally, it is important to emphasize that two of the main characteristics of emerging risk are low scientific knowledge and high scientific uncertainty. In this way, this book represents a step forward to improve knowledge and reduce the uncertainty around the management of emerging public health issues and risks. In the future, this step will have to be accompanied by new multidisciplinary approaches and advances that will continue to promote populations’ safety, security, health, and welfare.

The Exposome: A New Tool for Improved Health Risk Assessment

Denis A. Sarigiannis¹,²,     ¹HERACLES Research Center on the Exposome and Health, Center for Interdisciplinary Research and Innovation, Aristotle University of Thessaloniki, Thessaloniki, Greece,     ²Environmental Health Engineering, Institute for Advanced Study (IUSS), Pavia, Italy

Chapter Outline

1. Introductionxxiv

1.1 What Is the Exposome About and How Can It Support Environmental Health Risk Assessment?xxiv

1.2 Worldwide Exposome Initiatives and Projectsxxiv

1.3 Methodological Advances in Modern Risk and Health Impact Assessment Related to Exposome Conceptxxvi

2. The Connectivity Approachxxvii

2.1 Overall Methodological Conceptxxvii

2.2 Assessment of the External Exposomexxviii

2.2.1 Environmental and Microenvironmental Assessment—Integration of Data and Modelsxxviii

2.2.2 Sensorsxxix

2.2.3 Agent Based Modelingxxx

2.3 Assessment of Internal Exposomexxx

2.3.1 Human Biomonitoringxxx

2.3.2 Multiomics, In Vitro Confirmatory Analysis and Exposure Biology Workflowxxxi

2.3.3 Internal Dose Modelingxxxiii

2.3.4 Bioinformaticsxxxiv

3. Application of the Connectivity Approach on Nanotoxicityxxxv

3.1 Resultsxxxvii

3.1.1 Biochemical and Immunological Responsesxxxvii

3.1.2 Gene Expression In Vitroxxxviii

3.1.3 Pathway Analysisxxxix

3.2 Discussion and Conclusionsxxxix

4. Conclusionsxl

Referencesxlii

Abstract

Connectivity introduces a new exposome-based paradigm for interdisciplinary scientific work in the area of environmental health risk assessment. This denotes an approach that builds on the exploration of the interconnections between the coexistence of multiple exogenous and endogenous stressors and the different scales of biological organization, coupling the two results in the final adverse health effect. This marks a clear departure from the conventional paradigm, which seeks to shed light on the identification of singular cause-effect relationships between stressors and health outcomes. It entails creating a new way of combining health-relevant information coming from different disciplines, including (but not limited to) environmental science, epidemiology, toxicology, physiology, molecular biology, biochemistry, mathematics, and computer science. According to the connectivity approach, all factors affecting internal and external exposomes are treated as covariates, rather than just as cofounders. The functional integration of these different information classes into a unique framework will result in understanding the complex interaction between genome and exposure to environmental factors. An application of the connectivity approach is shown regarding toxicity assessment of nanomaterials, where multiple assays, multiomics data from humans, and in vitro data are used for elucidating the respective toxicity mechanisms.

KeywordsChemical mixtures, Cumulative exposure, Exposome, Multiomics, Public health

1. Introduction

1.1. What Is the Exposome About and How Can It Support Environmental Health Risk Assessment?

The exposome (Wild, 2005) represents the totality of exposures from conception onwards, simultaneously identifying, characterizing, and quantifying the exogenous and endogenous exposures and modifiable risk factors that predispose to and predict diseases throughout a person's life span.

The exposome came as a complement to the human genome; although decoding of the human genome (Schmutz et al., 2004) increased our understanding on the underlying causes of disease, the former explains only a limited percentage of the health burden of the population. Environmental factors are equally or eventually more important, and what is actually critical is the interaction of environmental factors with biological systems. Toward a better understanding of the causal links among the genome, the environment and human disease, unraveling the exposome implies that both environmental exposures and genetic variation are reliably measured simultaneously.

1.2. Worldwide Exposome Initiatives and Projects

Unraveling the exposome is daunting, particularly in the light of the enormous amount of information that needs to be integrated. As a result of dedicated actions and projects following the European Commission's (EC) Environment and Health Action Plan (EHAP) 2004–10, various harmonization efforts have occurred. Projects such as COPHES (harmonization of HBM), EHES (harmonization of Health Surveys), EU-menu (harmonization of data collection on food consumption), CHICOS (harmonization of child cohort studies), or U-BIOPRED (unbiased biomarkers in prediction of respiratory disease outcomes) all aim at providing common ground for the often disparate information that was scattered across Europe. In addition, European twin registries have collected biological material and longitudinal phenotypic and exposure data on tens of thousands of twins, providing a valuable resource for investigating the development of complex phenotypes and their underlying biology. The HEALS project is a logical progression from many of the achievements of the EHAP 2004–10. Making optimal use of the availability of harmonized data across Europe, HEALS introduces significant advances to environmental and health data fusion, including assimilation of data from satellite remote sensing for direct measurement of environmental exposure to airborne pollutants such as particulate matter (PM) and for providing accurate spatially resolved estimates of population exposed to environmental pollutants.

Two other projects comprise the EU exposome initiative, namely Exposomics (led by Imperial College, in London, UK) and HELIX (led by CREAL in Barcelona, Spain).

Exposomics focuses on the development of a systematic way to measure the influence of environmental exposures on health. Toward this aim, Exposomics deals with the development of a personal exposure monitoring (PEM) system (including sensors, smartphones, geo-referencing, satellites) for collecting data on the individual external exposome as well as on analyzing biological samples (internal markers of external exposures) using multiple omics technologies. Relationships between external exposures (as measured by PEM) and global profiles of molecular features (as measured by omics) in the same individuals constitute the overall methodology (Vineis et al., 2013), opening the way to exposome-wide association studies. The ultimate goal is to use the new tools in risk assessment and in the estimation of the burden of environmental disease with a special focus on the molecular epidemiology of cancer (Chadeau-Hyam et al., 2013; Vineis and Wild, 2014).

The Human Early Life Exposome (HELIX) project (Vrijheid et al., 2014) is a collaborative research project that aims to implement novel exposure assessment and biomarker methods to characterize early life exposure to multiple environmental factors and associate these with omics biomarkers and child health outcomes, characterizing thus the early life exposome. HELIX uses a multilevel study design, drawing on nested study populations on four different levels of data collection, including data from existing, as well as from an originally designed, subcohort for HELIX that includes 1200 mother–child pairs (Vrijheid et al., 2014). Similarly to Exposomics, a wide array of external and internal exposome assessment strategies were applied.

A fourth project, the Cross-Mediterranean Environment and Health Network (CROME), was also part of the EU-funded exposome projects albeit with a regional focus on the Mediterranean basin. CROME focused on integrating human biomonitoring measurements into the exposome construction process as a means to shed more light into the links between environmental and dietary exposures to toxic metals and persistent organic chemicals and adverse health outcomes with emphasis on cancer (Sarigiannis et al., 2015a,b) and neurotoxicity (Pino et al., 2017).

Health and Environment-wide Associations Based on Large population Surveys (HEALS) is the largest ongoing project on exposomes worldwide. HEALS brings together a comprehensive array of novel technologies, data analysis and modeling tools that support the efficient design and execution of large-scale exposome studies. The HEALS approach brings together and organizes environmental, socioeconomic, exposure, biomarker, and health effect data; in addition, it includes all the procedures and computational sequences necessary for applying advanced bioinformatics coupling advanced data mining, biological and exposure modeling so as to ensure that environmental exposure–health associations are studied comprehensively. The overall approach is verified in a series of population studies across Europe, tackling various levels of environmental exposure, age windows and gender differentiation of exposure, and socioeconomic and genetic variability. The main objective of HEALS is the refinement of an integrated methodology and the application of the corresponding analytical and computational tools for performing environment-wide association studies in support of EU-wide environment and health assessments (Sarigiannis, 2017). The HEALS approach is refined on the basis of preexisting population data, and then it will be applied in a pilot environment and health examination survey covering 18 EU member states. The lessons learned will be translated into scientific advice toward the development of protocols and guidelines for the setting up of a European environment and health examination survey.

In the United States, there are two main exposome-related initiatives funded by NIEHS, namely the HERCULES center at Emory University in Georgia and the Exposome Research Center at the University of California at Berkeley. HERCULES takes a multifaceted approach to the exposome, attempting to estimate the allostatic load from environmental exposures over an individual's life course. The UC Berkeley Center instead focuses on refining untargeted metabolomics as the main technological means toward unraveling the individual exposome and linking it to human disease by adopting a top-down approach (Rappaport and Smith, 2010).

1.3. Methodological Advances in Modern Risk and Health Impact Assessment Related to Exposome Concept

The advent and the further understanding of the exposome concept resulted in several advances in the field of risk and health impact assessment. Starting from human biomonitoring, which is the cornerstone of exposome studies, it has been highlighted that both traditional and exposomic biomonitoring approaches have key advantages and disadvantages for assessing exposure (Dennis et al., 2017). Exposome-based-omics approaches differ from traditional biomonitoring methods in that they can include all exposures of potential health significance, whether from endogenous or exogenous sources. Issues of sample availability and quality, identification of unknown analytes, capture of nonpersistent chemicals, integration of methods, and statistical assessment of increasingly complex data sets remain challenges that must continue to be addressed. However, biomonitoring itself and the big data generated from the comprehensive analysis of human biosamples, are not able to elucidate the relevant information if they are not supported by the appropriate computational tools (Manrai et al., 2017); these pertain to both the tools able to provide the mechanistic link for both external-internal exposure association (Sarigiannis et al., 2015a,b, 2016), as well as the ones able to derive a biological context of the molecular mechanisms exerting toxicity and resulting in adverse outcomes (Sarigiannis, 2015a, 2015b; Sarigiannis and Salifoglou, 2016). Significant improvements have also been associated with external exposure. Toward this aim, there is the use of personal sensors (Loh et al., 2017) for a more complete description of the individual space-time lines. However, similarly to HBM and omics data, interpretation of sensors signals using machine learning techniques (Sarigiannis et al., 2009; Stamatelopoulou et al., 2018) results in the optimal exploitation of the very dense information collected toward refined external exposure assessment. However, despite the progress in the individual technological components that relate to exposome analysis, it is a common understanding that researchers must overcome many practical barriers to apply them in large-scale population studies (Cui et al., 2016). To perform exposome-informed epidemiological studies, untargeted data-driven approaches in conjunction with dimension reduction techniques need to be developed and refined; in this way, the exposome concept presents numerous advantages against major limitations of conventional epidemiology, such as exposure misclassification, complex interactions between exposures (Sarigiannis and Karakitsios, 2018), and causal inference (Kim and Hong, 2017). Especially with regard to real-life cumulative exposures, it has been widely accepted that current risk and health impact assessment is moving away from a one-chemical one-health outcome model toward a new paradigm of monitoring the totality of exposures that individuals may experience over their lifetime (Johnson et al., 2017). Understanding how multiple exposures contribute to ways far different than additivity requires an exposure biology analysis for understanding the various converging pathways of toxicity; employing adverse outcome pathways (AOPs) concept toward the direction of identifying the common key events among intersecting pathways of toxicity (Escher et al., 2017) would result in a better understanding on how lifelong combined exposure to mixtures of nonhomologue compounds results in adverse health effects at various life stages and particularly during windows of susceptibility. The importance of windows of susceptibility has resulted in concretized methods for improving the timing of molecular snapshots, such as the ones proposed by Shaffer et al. (2017); the so-called Lifestage Exposome snapshots concept focuses on windows of susceptibility for particular target organ systems.

Although the concept of exposome was coined in 2005, interest in it gained momentum after 2011 (Kiossoglou et al., 2017). However, the concept itself, allowed significant room for interpretation by the various research groups, usually reflecting their domain of capacities and limitations. Focusing on the key exposome concept that pertains to the identification of the contribution of the totality of lifelong exposures toward human health, understanding the underlying biology, a comprehensive approach (the so-called connectivity approach) for developing the individual exposome is presented in this chapter.

2. The Connectivity Approach

2.1. Overall Methodological Concept

The overall methodological concept of the connectivity approach and the different arrays involved is graphically illustrated in Fig. 1.

This includes a wide array of state-of-the-art technologies across all major disciplines of the environmental exposure, biochemistry, molecular biology, toxicology, bioinformatics, and epidemiology arena. The exposome is actually a methodological tool to functionally integrate the different types of exposure information and to channel it through workflow aimed at providing additional insights on the environmental causes of diseases. Environmental exposure puts pressure on living organism functions. The genome defines how the organism will respond under the continuously changing environmental pressures. Biomarkers