BackgroundRecently, natural moisturizing factors (NMFs) and corneocyte surface topography were suggested as biomarkers for irritant dermatitis.ObjectivesTo investigate how exposure to different irritants influences corneocyte surface topography, NMF levels and the barrier function of human skin in vivo.MethodsEight healthy adult volunteers were exposed to aqueous solutions of 60% n‐propanol, 0.5% sodium lauryl sulfate (SLS), 0.15% sodium hydroxide, and 2.0% acetic acid, and distilled water, in a repeated irritation test over a period of 96 hours. Erythema, transepidermal water loss (TEWL), skin hydration, the dermal texture index (DTI) and NMF levels were measured at baseline, and after 24 and 96 hours.ResultsSLS and sodium hydroxide had the most pronounced effects on erythema and TEWL. Although n‐propanol caused only slight changes in TEWL and erythema, it showed pronounced effects on skin hydration, NMF levels, and the DTI. NMF was the only parameter that was significantly altered by all investigated irritants. The changes in the DTI were inversely associated with NMF levels and skin hydration.ConclusionSkin barrier impairment and the inflammatory response are irritant‐specific, emphasizing the need for a multiparametric approach to the study of skin irritation. NMF levels seem to be the most sensitive parameter in detecting irritant‐induced skin barrier alterations.

Alcohol-based disinfectants and detergents are common workplace factors for irritant contact dermatitis (ICD). Though occlusion and water are relevant co-exposures, the tandem effects of occlusion and sequential exposure to alcohols and detergents have not been studied. We therefore investigated the combined effects of occlusion with water and repeated exposure to n-propanol and/or sodium lauryl sulphate (SLS) in an occlusion-modified tandem irritation test. The outcomes included visual scoring, measurement of erythema, transepidermal water loss, capacitance and natural moisturizing factor (NMF) levels. Occlusion abrogated the skin barrier function and significantly enhanced the irritant-induced barrier damaging effects. The NMF levels of all irritant-exposed fields decreased significantly compared with the non-exposed fields; occlusion enhanced the decrease in NMF. Although SLS exerted more pronounced effects on the measured parameters, the barrier function impairment and NMF decrease after exposure to n-propanol in workplace-relevant concentrations, found in the study, confirm the significance of short-chain aliphatic alcohols for occupational ICD.

Background: Recent studies provide evidence for significant and previously underestimated barrier damaging effects of repeated exposure to 60% n-propanol in healthy skin in vivo.Objectives: To investigate further the cumulative effects of a range of n-propanol concentrations relevant at the workplace in healthy and atopic dermatitis (AD) individuals, and study the modulation of the outcomes by co-exposure and host-related factors.Methods: Healthy adult and AD volunteers were exposed to n-propanol concentrations from 30% to 75% in occlusion-modified tandem repeated irritation test with measurements of erythema, transepidermal water loss, capacitance, and the natural moisturizing factor (NMF) levels at baseline and after 96 hours.Results: n-Propanol exerted significant barrier damaging effects even at the lowest concentration in both groups. Exposure to all n-propanol concentrations significantly reduced the NMF levels. Preceding low-grade trauma by occlusion/water exposure reduced the skin irritation threshold in both groups. The differences in the severity of the barrier function impairment after exposure to the same concentrations under the same conditions between the AD and control groups were significant. Conclusions:The negative effects of cumulative exposure to n-propanol in healthy and atopic skin shown in the study suggest the need for critical re-evaluation of its irritant properties in vivo. K E Y W O R D S alcohol-based hand disinfectants, atopic dermatitis, irritant contact dermatitis, natural moisturizing factors, skin barrier 1 | INTRODUCTION Alcohol-based hand disinfection, repeated washing, and occlusion are important extrinsic factors for development of cumulative irritant hand eczema (HE) and contribute significantly to the sum of events leading to clinically manifest work-related HE in professions with relevant exposure. n-Propanol (1-propanol) is a short-chain alcohol and a common constituent of workplace or household hand disinfectants.Similar to isopropanol (2-propanol) or ethanol, n-propanol exerts antimicrobial effects at a broad concentration range from 15% up to 85%.Maryam Soltanipoor and Tasja Stilla contributed equally to this study.

Irritant damage to the permeability barrier elicits a cascade of responses that could be investigated by minimally invasive in vivo methods providing different information on biochemical and functional levels. Recent studies have shown that parallel to impairment of the barrier function and reduction of the natural moisturising factor (NMF), irritants such as the anionic detergent sodium lauryl sulfate (SLS) influence the corneocyte surface topography, investigated by atomic force microscopy and expressed by the Dermal Texture Index (DTI). To extend these findings, we investigated the early and late effects of different water soluble irritants on the barrier function, DTI, NMF and primary cytokine levels in healthy volunteers exposed to 60% N-propanol, 0.5% SLS, 0.15% sodium hydroxide, 2.0% acetic acid and occlusion with water in a controlled tandem repeated irritation test (TRIT) over 96 h. The irritant response was assessed by measuring erythema, transepidermal water loss (TEWL) and capacitance at baseline, 24 h and 96 h later; the cytokine levels, NMF and DTI were assessed in tape strips, collected at the same time points from the irritant-exposed and non-exposed sites. The magnitude of effects exerted by the irritants on the barrier integrity and properties, primary cytokine levels and DTI, found in the study, differed significantly, based on the chemical characteristics. The changes in DTI correlated with the NMF levels while being less influenced by inflammation. Though the observed differences may be influenced by the applied irritant concentration, our results confirm the need for a multi-parametric approach in the characterization of the irritant-specific barrier response and identification of sensitive outcome parameters for studying skin irritation in vivo.