Fumitox

Smokes are widely used, not only for military operations to screen and obscure objects or for signaling, but also for civilian applications such as, for example, security, protection or recreational use. Because of the recognized health risks for military and civilians exposed to smokes containing hexachloroethane, a variety of alternative smokes and obscurants have been developed. However, the potential hazards of inhalation of these new smokes are poorly characterized. Consequently, the aim of this project is to evaluate the toxicological effects following inhalation of particles emitted during the combustion of obscuring and screening smokes using an original transversal approach to take into account the physico-chemical characteristics of the aerosols and the biological targets predictive of adverse effects in human. The inhalation toxicity of atmospheric pollutants is conditioned to a great extent by the chemical composition and, in case of solid particles, by their size which determines the location where they settle in the respiratory tree. This is why we will determine the size features of particles in the cloud of smoke and the physicochemical features of fractions of particles from smokes after on-site specimen collection, after a validation step of technical work of sampling. The development of alternative methods to animal testing is nowadays an European priority, in particular in the field of inhalation toxicology. This is why we will evaluate the in vitro toxicity of removed samples, using human respiratory epithelium in primary culture (2D model) or differentiated reconstituted respiratory epithelium (3D model). The toxic response will be assessed through the use of biological markers typical of different cell and tissue toxicity mechanisms that can be involve in early (inflammation/oxidative stress) or typical of long-term effects (genotoxicity, morphologic and functional alterations). This project will provide new knowledge on toxicity of smokes. Moreover this work will give major insight in the field of evaluation of inhalation toxicology concerning particulate pollution thanks to the use of in situ methods of sampling, adapted for different kinds of aerosol and validated in terms of size characterization. Finally, this project will allow to get new pieces of information in the framework of the development of alternative methods to animal testing with the aim of evaluating the inhalation toxicity of atmospheric aerosols thanks to the use of new human primary cultures and of reconstituted respiratory epithelia and to mastered patterns of exposure.