In Vitro Percutaneous Absorption of Dehydroacetic Acid and Benzoic Acid From Pig Skin Using the Franz Diffusion Cell System

ABSTRACT Dehydroacetic acid (DA) and benzoic acid (BA) are used as preservative agents in cosmetics in Korea at maximum concentrations of 0.6% and 0.5%, respectively. Prior to conducting the percutaneous absorption study, analytical methods were developed and validated for the quantification of DA and BA in various matrices including swab (SW), stratum corneum (SC), full‐thickness skin (dermis + epidermis, SK), and receptor fluid (RF). These methods demonstrated excellent linearity ( r 2 = 0.9992–0.9998 for DA, 0.9996–0.9999 for BA), high accuracy (91.53%–111.70% and 96.04%–101.47%), and acceptable precision (1.90%–10.16% and 1.30%–5.48%), in accordance with regulatory validation guidelines. Percutaneous absorption was evaluated using a Franz diffusion cell system with dermatomed dorsal minipig skin. Lotion formulations containing DA (0.12%, 0.24%, and 0.6%) and BA (0.1%, 0.2%, and 0.5%) were topically applied at 10 mg/cm 2 . After 24 h of exposure, concentrations of each compound in the matrices were quantified using liquid chromatography–tandem mass spectrometry (LC–MS/MS). The total percutaneous absorption rates of DA were 104.13% ± 5.86%, 91.42% ± 4.05%, and 101.18% ± 7.82% for the 0.12%, 0.24%, and 0.6% formulations, respectively. For BA, the corresponding absorption rates were 74.71% ± 14.78%, 51.54% ± 8.97%, and 79.10% ± 5.65%. [Correction added on 14 April 2026, after first online publication: The first absorption rate in the preceding sentence has been updated in this version.] This indicates that DA and BA were mostly absorbed through the skin within the permitted concentration limits, suggesting that consideration of skin absorption rate is important when evaluating the safety of preservative exposure through the skin.