Efficacy-Toxicity Trade-Offs in Surfactant Formulation: Quantifying Irritation Synergy and Functional Performance in SLS/LDAO Binary Mixtures

Surfactant‑induced skin irritation remains a major toxicological concern in cosmetic and cleansing formulations, particularly those based on anionic surfactants such as sodium lauryl sulfate (SLS). In this study, the irritation‑mitigating potential of binary mixtures of SLS and the amphoteric surfactant lauryl dimethylamine oxide (LDAO) was systematically evaluated, with special emphasis on the quantitative assessment of synergistic effects related to protein denaturation and skin compatibility.

Binary SLS/LDAO mixtures at different ratios were characterized in terms of critical micelle concentration (CMC), surface tension, foam generation and irritant potential using the Zein protein denaturation test. In addition, interaction parameters associated with mixed micellization and interfacial adsorption were calculated to quantify the degree of physicochemical synergy. All mixtures exhibited a marked reduction in CMC and minimum surface tension compared to the individual surfactants, indicating the formation of thermodynamically stable mixed micelles. Negative interaction parameters confirmed strong attractive interactions between SLS and LDAO in both micellar (b^M) and interfacial domains (b^S).

From a toxicological perspective, the Zein test revealed a pronounced decrease in protein denaturation with increasing LDAO content. Importantly, the experimentally determined Zein values of the mixtures were significantly lower than the cumulative values calculated from the individual surfactants at equivalent concentrations, demonstrating a clear synergistic reduction of irritant potential. This effect was especially pronounced in mixtures rich in LDAO (60:40 and 50:50), which shifted the classification from irritant or moderately irritant to non‑irritant systems.