Decoding Tattoo and Permanent Makeup Pigments: Linking Physicochemical Properties to Absorption, Distribution, Metabolism, and Elimination Profiles Using Quantitative Structure–Activity Relationship (QSAR)‐Based New Approach Methodologies (NAMs)

The safety and quality of tattoo and permanent makeup (PMU) pigments are subject to increased scrutiny due to their potential to cause adverse effects like anaphylaxis, photoallergic responses, and long‐term toxicity. These undesirable reactions governed by their chemical structure possess varied physicochemical properties and absorption, distribution, metabolism, and elimination (ADME) characteristics. These properties control the pigment behavior during application, stability, and interaction with human tissue. The correlation between these physicochemical characteristics and ADME parameters of tattoo/PMU pigments remain under‐explored despite the current advances in toxicology. Our study aims to address and bridge the gap by leveraging open‐access QSAR computational toxicology tools like SwissADME and ChemBCPP to assess the ADME profiles of 90 synthetic tattoo/PMU pigments. We recruited techniques such as principal component analysis, correlation analysis, and hierarchical clustering. Furthermore, the intricate relationships between physicochemical properties, such as boiling point, density, solubility, and vapor pressure, and ADME behaviors spanning skin and gastrointestinal absorption, octanol coefficient, and more was explored. Our findings reveal significant systemic links associated with pigment properties and offer a data‐driven pipeline for safer pigment selection. The complex relationship between ADME and physicochemical properties was visualized by computing a correlation matrix. This revealed a strong positive correlation between properties such as lipophilicity and skin penetration for pigment epidermal absorption, viscosity, and flashpoint, essential for pigment stability, while negative correlations between vapor pressure and viscosity highlighted potential risks associated with pigment volatility. This approach strengthens the applications of new approach methodologies in the tattoo and PMU pigment functional insight, by developing in silico analytical pipelines and manufacturing safer, high‐quality ink development.