Cosmetic preservatives: physicochemical descriptors, mechanistic toxicity, and methodological approaches.

Cosmetic preservatives are widely used to ensure microbiological stability, yet their health risk assessment requires an understanding of dermal penetration mechanisms, interactions with the skin barrier, and cellular responses. This review presents mechanistic aspects of toxicity across major preservative classes, including parabens, formaldehyde donors, benzyl alcohol and its derivatives, isothiazolinones, sorbic acid, and benzoic acid systems, integrating physicochemical descriptors with data on percutaneous penetration, stratum corneum (SC) retention, and systemic distribution. Key parameters such as log P, log D, bioconcentration factor, and molecular weight are discussed as predictors of preservative behavior within the SC and their toxicodynamic potential. Mechanisms of cytotoxicity, sensitization, and membrane disruption are examined in relation to the chemical structure and reactivity of individual compounds. Alternative preservation strategies, including bioactive substances, multifunctional agents, and self-preserving systems, are evaluated with respect to their physicochemical properties and biological activity. Broader determinants of preservative use, such as exposure patterns, regulatory pressures, and environmental considerations, are outlined to contextualize mechanistic findings within real-world applications. The conclusion highlights future research directions, including the potential of methods such as Langmuir monolayer modeling, lipidomics, and established in vitro and ex vivo systems to support more precise characterization of preservative-barrier interactions and advance predictive toxicology.