The ubiquitous presence of disposable plastic items in everyday life, combined with inappropriate waste management and the persistence of conventional plastics, has led to a considerable accumulation of plastic in the environment. In nature, plastic waste is exposed to physicochemical and biological stresses that lead to its gradual degradation into micro- and nanoplastics (MNPs). Due to their large specific surface area and hydrophobic nature, MNPs have the ability to carry environmental contaminants on their surface, such as persistent organic pollutants, pathogens, or heavy metals. Because of their ubiquitous nature, human exposure to MNPs is a daily occurrence, mainly through inhalation of polluted air and ingestion of contaminated food and drink, such as bottled water, seafood, salt and honey. Although human exposure to plastic particles is now accepted, the consequences for the body are not yet well understood.

This thesis project was conducted to evaluate, under realistic environmental conditions, the biological effects of polyethylene terephthalate (PET) particles derived from plastic water bottles and commercial particles of polylactic acid (PLA), a biosourced and biodegradable plastic. These particles, ranging from 100-500 nm, were artificially aged in a Q-SUN climatic chamber simulating solar irradiation and the temperature of a sunny day at noon at the equator. Nickel, copper and tributyltin were chosen as models of toxic metal ions, because they are ubiquitous contaminants in the environment that pose problems in terms of food safety. The toxic effects of these plastic/metal combinations were assessed on co-cultures of Caco-2/HT2-MTX, two human intestinal epithelial cell lines. Two types of Caco-2 were used, representative either of healthy individuals (wild-type NOD2 gene) or of patients with a genetic predisposition to Crohn's disease, a chronic inflammatory bowel disease (NOD2 gene mutated at position 1007fs).

The effects of accelerated ageing on the physicochemical properties of the particles were characterized by various complementary methods: transmission and scanning electron microscopy, dynamic light scattering, zeta potential characterization and HPLC-MS/MS. Adsorption/desorption interactions between MNPs and metals (copper and tributyltin) were quantified by ICP-MS. Finally, the biological effects of combined exposure to pristine or aged particles, alone or in co-exposure with copper and tributyltin, on a model of intestinal epithelium were assessed. Various cellular parameters were monitored, including cell viability, DNA breaks, the level of intracellular reactive oxygen species, the inflammatory state of the cell and the integrity of the intestinal barrier.