Assessment of Dermal Permeation of Methamphetamine Hydrochloride in Human Skin

Environmental contamination with methamphetamine in residential and occupational settings raises public concerns, particularly regarding potential dermal exposure risks. This study evaluated dermal permeation through human skin and assessed associated risk implications. Using a Franz diffusion cell system, methamphetamine permeated into receptor chambers following 24-hour exposure, yielding low cumulative dermal permeation (DP) of 1.3±1.0 % with substantial inter-donor variability (e.g., Donor 1: 1.9±0.3 % vs. Donor 2: 0.90±0.85%, both collected from abdominal skin from human donors). Permeation was significantly lower than perfluoroalkyl substances (PFAS) like perfluorobutanesulfonamide (FBSA, 4.8%) and comparable to perfluoropentanoic acid (PFPeA, 1.1%). Biotransformation of methamphetamine to amphetamine was limited, with amphetamine concentrations in the receptor chamber consistently below LODs. Mechanistic analysis suggested that while molecular weight governed baseline diffusivity across compounds, methamphetamine’s high pKa (9.87) strongly influenced its limited skin permeability. Risk assessment using realistic dust concentrations estimated negligible dermal daily intake (1.2 μg/day) relative to inhalation exposures and health-based thresholds. Nevertheless, continuous low-level absorption through the skin may contribute to chronic exposure, highlighting the need for mitigation strategies in contaminated environments.