What does the concept of the exposome contribute to the understanding of chronic diseases?
Pr Robert Barouki, Professor at Paris University, Research Unit Director at INSERM, and chair of the ANSES Working Group on the Exposome
If we take the example of cancer, the genetic causes are now relatively well known, whereas non-genetic factors are still very unclear! For the first time, the concept of the exposome opens up the possibility of studying all the exposures to which individuals are subjected throughout their lifetime. Associating the temporal dimension with multiple exposures offers a global view of the causes of these diseases. How can research reflect this practically? A variety of approaches, research projects and cohort studies are currently being conducted worldwide. All this work can be used to document and model exposure to various hazards, whether chemical, biological, physical or psycho-social, in urban, rural or work environments for example. This research goes far beyond the combined effects of different chemicals.
« The challenge is to understand how an exposure at one point in time will have effects much later in our lifetime »
The key to answering this challenge is likely to be found in epigenetics. These are changes to the molecular environment of the genes that do not change the sequence itself. Epigenetic changes are relatively stable, heritable from cell to cell and influence gene expression. They can occur following a stressful event, remain present for a long time afterwards and are expressed according to the physiological state of the body, sometimes years or decades later.
Beyond research, it is important that health and safety agencies such as ANSES continue to explore these issues. The challenge lies in knowing which exposures have the greatest impact on our long-term health and to act accordingly to prevent the associated diseases. ANSES's Working Group on the Exposome is one of the first to attempt to take this concept into consideration when assessing health risks.
What research on the exposome does ANSES fund?
Laetitia Dubois, Director of the Research Funding & Scientific Watch Department
With the PNR EST National Research Programme for Environmental and Occupational Health, we fund research projects every year to gain a better understanding of the exposures in our daily environment and their effects on health. We address issues such as air quality, chemicals in our environment and in consumer products, radio frequencies and 5G, occupational health, etc. The data and knowledge from this research must be directly usable to assess risks and support management measures. The exposome is a vast area of study that requires the funding of research projects, as the data they provide will help us to understand it better. To study the cumulative effects of several stress factors and their interactions, it is also important to document the effects of each factor individually. The concept of the exposome helps us to focus on areas where there is a particular data gap concerning lesser-known effects, such as the impact of co-exposure to microbiological and chemical agents on human health.
« The concept of the exposome helps us to focus on areas where there is a particular data gap concerning lesser-known effects »
To really document the exposome, it is necessary to study the impacts of multiple exposures and the interactions between the different types of chemical, physical and biological hazards or stress, organisational constraints in the workplace and socio-economic conditions. It is also necessary to determine the windows of exposure, i.e. the times in life when an individual is most vulnerable. We have been able to determine, for instance, that infants are more sensitive to the effects of bisphenol A. The topic of endocrine disruptors is actually one of the main focuses in our calls for projects. Since 2011, it is estimated that almost half of the funded projects have managed to shed light on the exposome.
Our most recent call for projects emphasises the importance of research into the exposome. The aim is to eventually be able to assemble all these research findings so as to establish a relationship between multiple exposures, diseases and times of life when people are more at risk. Today more than ever, in an increasingly polluted environment with rapid technological developments, it is essential to boost research funding. We must be able to ensure that science keeps in step with our society.
What are the objectives of the Working Group on the Exposome?
Dr. Amélie Crépet, Scientific Project Leader, Risk Assessment Department
The aim of this working group (WG) is to help integrate considerations of the exposome into ANSES's expert appraisal work. The idea is to help the Agency gradually change the way it addresses the health issues it is asked to deal with, by proposing a global and temporal approach to exposure and risk. The exposome contains so many components that it is necessary to understand them step by step.
« The WG is helping us gradually change the way we address health issues»
This is why the WG is working on proposing actions to ANSES in the more or less long term to raise the awareness of expert committees and gradually introduce into expert appraisals the various components of the exposome, such as multi-source, multi-substance and multi-hazard exposures, which depend on lifestyle and the urban/rural or social environment, etc. In this context, it recommends the development of methods and operational tools as well as the production of the data needed. It has also suggested issues to be investigated in the framework of PNR EST studies. Obviously, the WG builds on what ANSES is already doing in terms of the exposome.
In addition, it is working to make concrete proposals to better address exposome issues in its ongoing expert appraisal work. For example, the Agency is currently working on the risks to workers involved in the collection, sorting and treatment of household waste. Not only are they concerned by risks linked to chemicals and biological agents, but they carry out activities that are often physically demanding. A debate on the psychological, biological and socio-economic factors that determine the mental health of these professionals will be included.
Another example concerns the effects of digital devices on the health of children and adolescents. This expert appraisal will attempt to assess effects on physical and mental health while integrating behavioural, socio-economic and family dimensions. Through an “exposome” approach, it is planned to analyse the way in which everyday chemical and microbiological substances (particularly those found in the home) may also contribute to the occurrence of disorders associated with the use of digital devices.
This multidisciplinary working group, composed of external scientific experts and ANSES coordinators, brings together risk assessors, toxicologists, microbiologists, epidemiologists, chemists/analysts, statisticians, sociologists, economists and more.