The objectives of the FLUOPATH project are 1) to find new biomarkers (promoeters that induce the expression of genes of interest) coupled to a fluorescent biosensor allowing to acquire new knowledge in bacterial cell physiology related to the impact of technological disturbances inducing stresses. The study will be focused on the growth, survival and virulence of two pathogens in dairy products (milk, diluted cheese and if possible solid cheese) and 2) to use this knowledge combined with the knowledge present in the scientific literature to improve the models for predicting the microbiological risk in dairy products. The pathogens considered will be L. monocytogenes and B. cereus. The matrices considered will be liquid milk as well as model diluted and undiluted cheese (gelified matrix). New models based on the use at the scale of the single cell and the whole population of biomarkers will be developed to predict growth, resistance and virulence (invasive capacity for L. monocytogenes and entry into sporulation and toxin production for B. cereus) to stress while taking into account cellular variability. A precise quantification of the impact of stressful industrial conditions will be carried out on bacterial responses at the cellular level: probability of single cell / whole poulation growth, survival, toxin production, spore formation, invasive capacity. The challenge is to design and validate in food matrices bacterial biomarkers of phenotypes of interest in risk assessment in order to incorporate the intensity of biomarker response into exposure assessment models.

The OLIGO project aims at stimulating and supporting a thorough risk assessment related to the dietary exposure of the French population to cyclic oligoesters migrating from polyester-based coatings into canned foodstuffs. It addresses a timely and important public health issue related to the chemical safety of food that has not yet been resolved Epoxy-resins based on bisphenol A (BPA) diglycidyl ether have traditionally been used worldwide in internal coatings applied to metallic food contact materials. Due to concerns of both consumers and the scientific community, restrictions have been applied at the EU scale on the use of BPA, including a ban in baby bottles and a drastic specific migration limit from plastics or varnishes and coatings to food. In France, a complete ban of BPA entered into force in 2015. Industrial stakeholders have conceded enormous efforts to adapt through the evolution of technologies and conservation processes. Polyester-based coatings have grown into predominant alternatives to BPA-based epoxy resins. A large range of polyol- and polyacid-monomers, for which migration into foodstuffs is under control, may be used, offering numerous polyester combinations. However, oligoesters, which are non-intentionally added substances (NIAS) constitutive of polyester-based coatings arising from incomplete polymerisation reactions (up to 2% of the resin's weight, mostly cyclic combinations of 4 to 8 monomers), have not yet been subjected to a robust and transparent risk assessment, their wide chemical diversity raising analytical issues. So far, missing data relate to (i) our knowledge on the extent of polyester-based coatings' use on the market (France standing apart), (ii) the comprehensive identification of oligoesters, (iii) the related human exposure following migration into food, and (iv) their fate (e.g. liver biotransformation and potential bioactivation triggering adverse effects). Within the project OLIGO, the main scientific bottleneck – the unavailability of representative authentic standards – will be tackled through the organic synthesis of native compounds as well as deuterium- and radio-labelled compounds, in order to (i) comprehensively identify the oligoesters present in marketed cans, (ii) quantify their migration into food and (iii) assess in vitro their metabolism and potential toxicity to human. Exposure assessment of the French population will be balanced with hazard identification aspects in order to establish a provisional risk assessment and further recommendations. Addressing the challenge of characterising NIAS such as oligoesters requires resources and information which are not available to most of the agro-industrial stakeholders. Five public and academic partners are involved in OLIGO. CEISAM (CNRS UMR 6230, Nantes) will provide other partners with a set of representative authentic standards to be synthesised stepwise. LABERCA (INRAE UMR 1329, Nantes) will coordinate the project and will achieve oligoesters’ identification in coatings and their quantification in foodstuffs. To this end, a previously developed workflow will be applied to identify oligoesters, with much attention paid to the sample preparation of foodstuffs. LNC (INSERM UMR 1231, Dijon) will study genotoxicity, performing in vitro regulatory bioassays based on OECD guidelines, and endocrine disruption potencies, performing bioassays of the level 2 (mode of action) of OCDE framework. TOXALIM (INRAE UMR 1331, Toulouse) will carry out in vitro human liver biotransformation assays (hazard identification, biomarker metabolites) and gain a broader understanding of the fate of oligoesters. ANSES, the French agency for food, environmental and occupational health & safety, will define a sound sampling plan and lead the output provisional risk assessment.

In France and worldwide, during COVID-19 pandemic workers in the agri-food sector are considered part of the essential workforce of critical infrastructures, and this concerns farmers as well as employees in processing plants, truck drivers who make deliveries as well as hypermarket cashiers. In addition, in some countries such as the US, by presidential decree, meat and poultry processing plants must continue to operate to avoid disruption to the food supply chain. The workers in these industries may be more exposed to coronaviruses because telework is not possible, and many face increased risks due to the proximity of their work environment. There is a need to carefully address the issue of virus circulation in meat processing plants in France from three perspectives: (i) protection of workers and avoidance of these premises becoming hotspots of virus circulation in the communities; (ii) prevention of the closure of these processing plants and ensuring supplies; and (iii) prevention of contamination of food in order to avoid the export of this virus to other locations. The main goal of this project is to gain insights on the circulation of SARS-CoV-2 in meat processing plants in order to provide preventive or risk mitigation measures for workers and consumers. We are planning to gather/collect the data necessary to understand the circulation of the virus in this type of workplace and to use them to build a simulation model of the propagation of the SARS-CoV-2. The present project will be organized into four work packages. First, the SARS-CoV-2 transmission and persistence factors in meat processing plants will be studied. The objectives of WP1 is to carry out an extensive literature review on SARS-CoV-2 transmission factors/parameters in order to extract relevant data for studying the circulation of the virus in meat processing plants and to define protocols to be conducted under laboratory conditions to overcome data gaps or uncertainties on certain virus transmission parameters/factors. In the second work package, a description of the conditions and environmental factors of work in meat processing plants will be done, through questionnaires and interviews (face to face) as well as observations, to be carried out in authentic food processing plants. The data collected will be used to provide directions and clarifications for the laboratory work carried out in WP1, and to populate the simulation model. The objective of WP3 is to construct a mathematical model to simulate the spread of the virus in a meat-processing plant in order to assess the impact of certain prevention or mitigation measures on the probability of transmission of the virus to employees and the contamination of products and the environment. This model will also allow us to explore the transmission of the virus outside the plants. The objective of the WP4 is to provide different critical communication mechanisms to engage employees in an effective safety management policy, gain cooperation and support, and maintain a positive safety culture. The impacts of this project will be 1) to increase the knowledge about how the virus is transmitted in a professional setting; 2) provide solutions to companies to better calibrate their preventive measures and mitigate the risks in the event of the introduction of the virus into their premises; 3)provide tangible data on transmission modalities and simulate the circulation of the virus according to different scenarios and 4) provide a decision support for business and government based on science and available data. The approach is extendable to other situations: processing plants, offices, universities, public places, etc.

Human and wildlife animals are exposed to multiple sources of environmental stressors including chemicals such as persistent organic pollutants (POPs) and endocrine disrupting compounds (EDCs). In addition to the important public health issues related to such exposures, EDCs are suspected to elicit ecosystems toxicity with an impact on the food chain and biodiversity and a significant economic burden linked to the increase of metabolic and neurodevelopmental disorders. In this complex and multifactorial context, new and innovative approaches are warranted to address potential linkages between such environmental exposure and health outcomes. Whereas exposure models in toxicology and ecotoxicology traditionally link a given external exposure source with a target organism, the vision of CREATIvE is to consider the organism as both an internal exposure source and a target. Specifically, its ambition is to assess potential health consequences from the release of POP mixtures from an internal storage site (the source) by understanding their complex biological modes of action (MoAs) on the target tissues of the same organism. It is well known that POPs bio-accumulate in living organisms and are stored in specific tissues e.g. adipose tissue (AT) brain, and liver, for long periods of time. Therefore, these tissues represent internal chronic sources of pollutants possibly leading to various disorders including metabolic and neurodegenerative diseases. Such “internal” exposures are not satisfactorily captured by current methods based on investigating different types of external POPs exposure via gavage, injection or acute inhalation. The proposed protocol will not replace the existing ones but will be complementary, taking into account for the first time internal sources of exposure. The aim of CREATIvE is to develop a novel strategy exploring the effects of an internal exposure from grafted contaminated AT. The kinetics and consequences from a redistribution of POPs and their metabolites from grafted contaminated AT on several tissues and organs, e.g. liver, brain and host AT will be studied. The proposed integrated approach is a combination of experimental studies (chemical quantitative measurements in tissues, metabolomics, transcriptomics) and computational modeling (PBPK and systems biology approaches). The advantage of developing such integrated approaches is the possibility to identify the systemic effects of internal mixture exposure at different biological levels, by mimicking the reality of human and animal exposure. As results, new biomarkers will be characterized, and novel complementary models will be proposed which will help at increasing Agregated Exposure Pathways (AEPs) information. To our knowledge such a strategy is clearly innovative and different from existing studies. In a recent preliminary study, an allograft model was developed at Paris Descartes, consisting in a mouse graft of contaminated AT to a non-contaminated mouse. We demonstrated that four weeks after transplantation, the grafts are vascularized and functional. In those initial studies, donor AT was contaminated by 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD), and we showed that this contaminant was indeed redistributed to different tissues with different kinetics. Based on this acquired proof of concept, CREATIvE will explore the kinetics of a low dose POP mixture release from an internal source of exposure, and most importantly will assess the toxic effects of such mixtures on other tissues and organs. After improvement of the experimental model, a mixture of twelve environmentally relevant POPs will be studied at low doses with the aim to better understand the consequences of POP mixture release from a unique internal source of exposure.

Endometriosis is a chronic hormone-dependent disease affecting 10% of women. Endocrine-disruptors have been suspected to play a role in endometriosis etiology, and several persistent organic pollutants (POPs) have been associated with endometriosis risk. However, despite experimental evidence of an impact of POPs on endometriosis lesion growth, no previous study has formally tested the hypothesis of an influence of POPs on the severity of endometriosis. POPENDO aims to examine associations between internal exposure levels of 4 families of POPs (dioxins, polychlorinated biphenyls, organochlorine pesticides, perfluorinated alkylated substances, totaling 81 substances) and endometriosis severity in a sample of 650 women participating in ComPaRe-Endometriosis, a prospective e-cohort of over 12,000 endometriosis patients. The findings will provide novel information on the impact of POP exposure on endometriosis that will contribute to inform prevention and reduce the impact of the disease.