Modulation of the Toxicity of Three Red Tattoo Pigments by Artificial Aging

Pigments used in tattoos represent a unique case of voluntary, long-term exposure to particles trapped in the skin. Evidence is accumulating that these compounds, and in particular red pigments, are associated with skin disorders and possibly cutaneous cancers. In the present work, we tested the hypothesis of degradation of pigments in the dermis that would lead to the release of diffusible nanoparticles or soluble degradation products. These species could then reach the epidermis and trigger physiological responses by impacting keratinocytes. Two degradation pathways of tattoo pigments were investigated in the present work, which combined physicochemical characterization and toxicological assessment in the HaCaT human keratinocyte cell line. The first pathway was the photodegradation of pigments that we explored in a previous work on Pigment orange 13 (PO13) and extended here to Pigment red 254 (PR254) and Pigment red 122 (PR122). While PR254 was photostable, PR122 was found to release toxic photoproducts. The second studied pathway was the possible degradation in the phagolysosomes of macrophages where pigment particles are stored in the skin. We did not observe degradation upon incubation in reconstructed phagolysosomal medium but rather found that the added immunoglobulins completely inhibited the cytotoxicity of PO13, PR254, and PR122. The observation of a drastic decrease in ζ potential strongly suggested the creation of a protein corona, which led to a decrease in cellular toxicity.