In vitro dermal absorption of acetylhexamethyl indan from a cosmetic cream formulation

Acetylhexamethyl indan (AHI; trade name, Phantolide; CAS No. 15323-35-0) is used globally as a fragrance ingredient in cosmetics up to 2% in Europe and Korea. Dermal absorption data are essential for calculating the systemic exposure dose (SED) in cosmetic risk assessment, but experimental data for AHI are currently unavailable. In this study, an in vitro dermal absorption test was conducted using a Franz diffusion cell with mini-pig skin, a widely accepted surrogate for human skin. Validated analytical methods were developed for the quantification of AHI in swab wash (WASH), stratum corneum (SC), skin (dermis + epidermis, SKIN), and receptor fluid (RF) matrices. The methods demonstrated excellent linearity (r² = 0.9965-0.9999), accuracy (85.5-112.4%), and precision (0.2-11.9%) in accordance with international validation guidelines. A cream formulation containing 2% AHI (actual concentration: 1.88%) was applied to the skin at a dose of 10 mg/cm², and after 24 h, each matrix was analyzed by liquid chromatography-tandem mass spectrometry (LC-MS/MS). The total dermal absorption rate of AHI was 1.78 ± 1.22%, which is markedly lower than the conservative default assumption of 50% absorption according to the Scientific Committee on Consumer Safety (SCCS). These findings support more accurate exposure estimation and risk assessment of AHI-containing cosmetics.