Systemic exposure to tattoo ink tracers was measured at 0.31 g per session, suggesting that prior ex vivo models, which estimated 4.31 g, may have significantly overestimated systemic exposure caused by cutaneous metabolism and ink exudation, according to a recent study. 

In the short-term clinical study, published in Archives of Toxicology, researchers examined the systemic exposure and biokinetics of tattoo ink components in human patients. They investigated the absorption, metabolism, and excretion of selected tracers—potassium iodide, 4-aminobenzoic acid (PABA), and 2-phenoxyethanol—when introduced into the skin via tattooing. These tracers were selected for their structural similarity to potentially hazardous compounds commonly found in tattoo inks.

The single-arm clinical trial enrolled 24 healthy male participants aged 18 to 45 years, all of whom had at least one prior tattoo. Professional tattoo artists applied black (n = 14) or red (n = 10) tattoo ink containing the tracers to an estimated 300 cm² (black) or 100 cm² (red) of skin. The researchers, led by Susanne Kochs, of the Department of Chemical and Product Safety at the German Federal Institute for Risk Assessment in Berlin, quantified systemic exposure by collecting blood and urine samples over a 48-hour period posttattooing. Urine collection was segmented into specific time intervals, while blood samples were drawn at predefined time points. Analytical techniques included high-performance liquid chromatography coupled with mass spectrometry for tracer metabolites and inductively coupled plasma mass spectrometry for iodine quantification. Additionally, peroral PABA metabolism was assessed in three separate patients, and in vitro assays examined fibroblast and macrophage metabolism of PABA.

All tracers or their metabolites were detected in urine within 24 hours. Plasma analysis revealed detectable levels of iodide and the PABA metabolite 4-acetamidobenzoic acid (ACD), though concentrations were near the limit of quantification, consistent with prior findings that suggested a role for cutaneous metabolism in altering systemic absorption compared with oral exposure. The mean estimated systemic exposure to ink components per tattoo session was 0.31 g (75th percentile) compared with the 4.31 g previously estimated in risk assessments. The researchers attributed the lower systemic absorption to cutaneous first-pass metabolism and ink exudation during wound healing, as evidenced by the presence of ink in wound dressings. This indicated that some ink may be eliminated prior to systemic absorption and may contribute to the lower systemic exposure observed in this study. Notably, peroral administration of PABA resulted in a higher percentage of ACD retrieval in urine (94.75% ± 3.54%) compared with tattooing (22.63% ± 1.84%). Fibroblasts and macrophages demonstrated the ability to metabolize PABA into ACD, revealing a cutaneous first-pass effect that altered the metabolic profile compared with gastrointestinal absorption. 

The findings provided initial in vivo human data on soluble tattoo ink exposure, with plasma concentrations of tracers near the limit of quantification. The researchers hypothesized that metabolism and transepidermal exudation may contribute to lower systemic exposure compared with prior estimates.

The authors reported no conflicts of interest.