Mass spectrometry imaging reveals uptake of the allergen methylisothiazolinone in ex vivo human skin

Allergic contact dermatitis (ACD) is a prevalent inflammatory skin condition triggered by allergens such as 2-methyl-4-isothiazolin-3-one (MI), a common preservative. The incidence of contact allergy to MI has fallen in Europe in recent years, attributable to government regulation limiting concentrations of MI I; however, incidence continues to rise in the USA. The pattern and extent of distribution of MI in skin is unknown and a better understanding of the effect of MI on the skin is needed. In this study NativeSkin Access® human skin biopsies were treated with MI, and Time-of-Flight Secondary Ion Mass Spectrometry (ToF-SIMS) analysis was performed to map the distribution of MI and assess changes in endogenous lipids. MI penetrates the stratum corneum and viable epidermis, with significant lipid alterations observed in the stratum corneum. The use of Argon gas cluster ion beam (Ar-GCIB) sputtering in the ToF-SIMS analysis improved the resolution and clarity of cellular structures, allowing for better visualization of MI penetration and its effects on skin lipids. The study highlights the utility of ToF-SIMS in combination with Argon gas cluster sputtering in visualizing allergen distribution and its impact on skin lipid composition, providing insights into the mechanisms of skin sensitization. • 2-Methyl-4-isothiazolin-3-one (MI) penetration in ex vivo human skin was analyzed • Time-of-flight secondary ion mass spectrometry (ToF-SIMS) was used for analysis of MI • Significant lipid composition changes was found in skin following MI treatment. • Enhanced imaging could be seen using Ar-GCIB sputtering in ToF-SIMS analysis.