Non-occlusive topical exposure of human skin in vitro as model for cytotoxicity testing of irritant compounds

• Published in: Toxicology mechanisms and methods 2016-02, Vol.26 (2), p.82-87
• Main Authors: Lönnqvist, Susanna, Briheim, Kristina, Kratz, Gunnar
• Format: Article
• Language: English
• Subjects: Administration, Cutaneous; Cell Survival - drug effects; Human full thickness skin; Humans; in vitro model; In Vitro Techniques; Irritants - administration & dosage; Irritants - pharmacokinetics; Irritants - toxicity; SDS; Skin - drug effects; Skin - metabolism; Skin - pathology; Skin Irritancy Tests - methods; Sodium Dodecyl Sulfate - administration & dosage; Sodium Dodecyl Sulfate - pharmacokinetics; Sodium Dodecyl Sulfate - toxicity; Time Factors
• ISSN: 1537-6516; 1537-6524; 1537-6524
• DOI: 10.3109/15376516.2015.1091537

Testing of irritant compounds has traditionally been performed on animals and human volunteers. Animal testing should always be restricted and for skin irritancy mice and rabbits hold poor predictive value for irritant potential in humans. Irritant testing on human volunteers is restricted by the duration subjects can be exposed, and by the subjectivity of interpreting the visual signs of skin irritation. We propose an irritant testing system using viable human full thickness skin with the loss of cell viability in the exposed skin area as end point measurement. Skin was exposed to sodium dodecyl sulfate (SDS) at 20% concentration by non-occluded topical exposure to establish a positive control response and subsequent test compounds were statistically compared with the 20% SDS response. Cell viability and metabolism were measured with 3-(4,5-dimethyl-thiazol-2-yl)-2,5-diphenyl tetrazolium bromide (MTT) assay. The model presents correlation between increased concentration of SDS and decreased viability of cells in the exposed skin area (R 2  = 0.76). We propose the model to be used for cytotoxicity testing of irritant compounds. With fully intact barrier function, the model comprises all cells present in the skin with quantifiable end point measurement.