Tattoos are showing a considerable rise in popularity, with 10 to 20% of the population in Europe and the United States bearing at least one tattoo. Tattoos consist of the intradermal injection of insoluble pigments, at both micro- and nanoscale, that persist in the body throughout life. Although tattooing is an ancient practice, concerns about its health impact have only recently emerged. The implementation of the European REACH regulation has led to increased monitoring of inks and pigments, yet our knowledge of their long-term cellular and molecular effects remains limited.
In this thesis, we focused on two mineral pigments that have been used since Antiquity, iron oxides and manganese oxides. Iron oxides are still used in tattooing, e.g. in permanent makeup and dermopigmentation after mastectomy. They are widely used for their shades that closely match skin tones. Few complications or delayed effects related to these pigments have been reported in the literature, but this does not guarantee their safety. Manganese oxides, although not used in tattooing, remain extensively produced for other sectors such as paints, ceramics, and batteries. Exposure to these particles differs from that of iron oxides but is no less concerning. Indeed, manganese dioxide is a proven neurotoxicant. While several studies have investigated its acute toxicity, delayed effects at lower doses remain poorly documented.
To investigate the potential effects of these pigments, we developed exposure schemes designed to assess delayed and/or long-term cellular responses. Macrophages were chosen as the cell model. These resident immune cells, present in most organs, belong to an evolutionarily ancient lineage. One of their main functions is phagocytosis, not only of pathogens but also of inert particles. They are therefore involved in the uptake and immobilization of the pigments injected during tattooing as well as the uptake of inhaled particles in the lungs. As sentinels of the organism, macrophages play a key role in regulating inflammation and maintaining tissue homeostasis. Any alteration of their functions could have major consequences, ranging from impaired immunity to granulomatous pathologies.
Our results highlight that macrophage responses vary depending on the pigment’s nature and physicochemical properties. Some iron oxides induce a prolonged inflammatory state, with persistent secretion of pro-inflammatory cytokines, whereas other pigments appear to be better tolerated. These differences suggest an important role of their solubility and chemical composition in shaping cellular responses, between persistent inflammation and metal storage mechanisms.
This work highlights the specific biological effects of these pigments. It demonstrates that such effects cannot be generalized, as they strongly depend on composition and manufacturing processes. It emphasizes the need for better characterization of their safety and more comprehensive evaluation of their potential impacts, not only at the injection site but also beyond, through their migration to lymphatic organs and interactions with adaptive immunity. More broadly, these findings contribute to a better understanding of the interactions between mineral particles and immune cells, and underscore the importance of considering pigment diversity in the assessment of risks related to tattoos and other environmental exposures.