Isothiazolinones as preservatives: physicochemical characteristics, biological activity, and safety assessment

Isothiazolinones are heterocyclic compounds with potent broad-spectrum antimicrobial properties, commonly used as preservatives in cosmetics, pharmaceuticals, and industrial products. Their antimicrobial efficacy results from interference with microbial protein and nucleic acid synthesis. However, their limited water solubility and instability under alkaline conditions, elevated temperatures, and UV exposure constrain their formulation and use. Despite regulatory restrictions, especially in the EU, due to their allergenic and toxic potential, exposure remains widespread, particularly through industrial and household products. Studies indicate that isothiazolinones can penetrate the skin, bind to cellular components, and induce oxidative stress, apoptosis, and immune responses. Furthermore, emerging data suggest possible endocrine-disrupting and neurotoxic effects. The mechanisms driving these toxicities are still not fully understood. This review examines the physicochemical characteristics, antimicrobial mechanisms, applications, exposure routes, cytotoxic effects, and molecular interactions of isothiazolinones. Deeper mechanistic insight is needed to support the development of safer alternatives and to inform more stringent regulatory frameworks.