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Percutaneous Penetration of Quaternary Ammonium Compounds (QACs) Using in Vitro Three-Dimensional Human Skin
Mengyao Ran1, Xinrui Leng1, Zhong Lv1
1State Key Laboratory of Soil Pollution Control and Safety, Shenzhen Key Laboratory of Precision Measurement and Early Warning Technology for Urban Environmental Health Risks, School of Environmental Science and Engineering, Southern University of Science and Technology, Shenzhen 518055, China.
Abstract:
Quaternary ammonium compounds (QACs) are widely applied to antimicrobial textiles, yet their dermal exposure profiles and skin effects remain poorly understood. Using a three-dimensional human skin equivalent (3D-HSE), we quantified percutaneous penetration for benzylalkyldimethylammonium compounds (BACs), dialkyldimethylammonium compounds (DADMACs), and alkyltrimethylammonium compounds (ATMACs) with C8-C18 chains. Shorter-chain (C8-C10) BACs and ATMACs showed rapid uptake (>50% at 24 h; >70% at 48 h), whereas long-chain homologues (C16-C18) exhibited minimal permeation (<15%) and greater retention within the skin. The correlation between the octanol-water partition coefficient (log Kow) and molecular weight (MW), combined with molecular docking analysis, revealed that both passive and active transport were involved in the skin exposure of QACs. By integrating sweat leaching and 3D-HSE data, estimated daily intakes (EDIs) of total QACs were 1.82 ng/kg bw/d for dry clothing, increasing to 96.9 ng/kg bw/d for sweaty clothing, while these values reached 51.3 and 1960 ng/kg bw/d in the high-exposure scenario, respectively. Finally, transcriptomics and lipidomics showed downregulation of keratinization and epidermal genes and broad depletion of structural and signaling lipids, consistent with impaired skin integrity and immune activation. These results identify textiles as a significant sweat-mediated exposure source and demonstrate chain-length-dependent dermal kinetics and toxicity of QACs.
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