SoEcohealth

This project focuses on Succinate DeHydrogenase Inhibitors (SDHI), a family of fungicides that has been increasingly used over the past ten years. SDHI share the feature of inhibiting the succinate dehydrogenase (SDH), a universal key mitochondrial enzyme involved in cellular respiration and the Krebs cycle. The catalytic region of the SDH is highly conserved across species: SDHI target mitochondrial functions that are not only critical in agricultural fungi, but also in all animals and plant species that have mitochondria. With respect to human health, genetic diseases and cancer genetics provide evidence that alterations of SDH activity (partial or total) lead to severe outcomes (neuropathies, renal diseases and cancers). Indeed, the loss of SDH activity is associated with an oxidative stress, a metabolic reprogramming and epigenetic remodelling due to succinate accumulation. Therefore, the off-target organisms of agricultural SDHI use are potentially be exposed to : i) mitochondrial dysfunction, ii) the accumulation of succinate, iii) a metabolic reprogramming and iv) epigenetic modifications. SoEcoHealth project has the ambition to propose an interdisciplinary approach with 9 partners, including challenges of public health and the preservation of biodiversity, to tackle the highly problematic question of pesticides use with the particular case of SDHI. SoEcoHealth aims at studying: 1- Environmental exposome. To set up quantitative and sensitive methods of detection of major SDHI and its metabolites and evaluate the presence of SDHI in water and food; 2- Human exposome. To determine whether urinary SDHI levels in farmers and in the general population correlate with the incidence of chronic diseases, notably Chronic Kidney Diseases 3- Mechanistic approaches. To characterize hazards of SDHI regarding a selected range of species. We will focus on mitochondria function and energy metabolism in humans, rodents, nematodes, fish, soil off-target fungi, pathogenic fungi and bees; 4- Improved the regulatory framework. To take advantage of the SDHI case study to improve risk assessment based on interdisciplinarity and co-construction of knowledge. The consortium includes chemistry, epidemiology, medicine, biochemistry, toxicology, ecotoxicology, economics and sociology. It will benefit from the decompartmentalization of their disciplines to contextualize the research and easily access the information relative to SDHI. The interdisciplinary seminars, in addition to the seminars dedicated to specific topics, will be the place to share knowledge and understand the methods of the studies with a common object in the center of the scientific forum that is the SDHI. The SoEcoHealth project deals with issues of occupational and public health and the preservation of biodiversity The case of SDHI studies in the context of an EcoHealth approach will constitute a proof of concept for a new way of risk assessment that could be extended to other pollutants. A closing project meeting dedicated to a broad public is planned and opened to the different stakeholders (citizens, farmers, non-governmental organisations, jurists, regulators, politicians). SoEcoHealth is likely to contribute to the improvement of food safety and global human health. By considering the impacts of SDHI on ecosystems, the project will result in new knowledge about the impact of SDHI on biodiversity, which will be related to human health too. By a better characterization of the hazard of SDHI, with a holistic view on living beings and the socio-economical evaluation of the risk assessment, this project will provide knowledge for the possible and desirable improvement of regulation to limit deleterious consequences on biodiversity and health.