The Permeable Lip: A Critical Knowledge Gap for Systemic Exposure to Lip Cosmetic Chemicals

The pervasive use of lip cosmetics results in chronic, low-dose exposure to complex mixtures of chemicals via multiple routes, yet current cosmetic safety regulations treat lip products as conventional topical applications to skin. While the EU safety assessment framework acknowledges ingestion as an exposure route for lip products, standardised lip-specific testing models do not currently exist. The US requires no mandatory pre-market safety review for cosmetic ingredients and systemic exposure consideration is confined to voluntary industry assessment (except for colour additives). In both jurisdictions, exposure estimates are based on usage data from 2005 that do not reflect current real-world usage patterns of lip cosmetics, including frequent reapplication, product layering, and marketing based on food characteristics. The unique physiology of the lips, which represent a transitional tissue between external skin and oral mucosa provides an additional exposure route: the vermilion and labial mucosa are characterized by a markedly thinner and incompletely keratinised epithelium, reduced lipid barrier components, high vascularisation, and constant moisture-collectively conferring substantially higher permeability than facial skin. Evidence from pharmacology demonstrates that oral mucosal tissues are deliberately exploited for rapid systemic drug delivery. By comparing how the oral mucosal exposure route is evaluated across cosmetic, food, and pharmaceutical regulatory regimes, this review identifies a critical regulatory gap: chemicals applied to the lips are assessed under frameworks designed for low-permeability skin, despite a biological reality more consistent with mucosal exposure. This mismatch undermines the accuracy of current risk assessments and may lead to systematic underestimation of internal dose for certain lip cosmetic ingredients including microplastics. Addressing this gap will require lip-specific exposure models, physiologically relevant in vitro systems, and updated regulatory guidance to ensure that cosmetic safety assessment accurately reflects the unique exposure profile of lip products.