Bernhofer, L., Juneja, C., Martin, K. In Vitro Toxicology and Pharmacology Group., Johnson & Johnson Consumer Products Worldwide, Skillman, NJ

The need exists for a rapid, accurate in vitro screening protocol, predictive for human skin irritation in response to topically applied products. The EPI-100, EpiDerm™ Human Skin Model System produced by MatTek Corp. (Ashland, MA) is being investigated for this purpose. This system consists of normal, human-derived epidermal keratinocytes (NHEK), grown on permeable cell culture inserts to form a multilayered, highly differentiated model of the human epidermis. Keratinocytes, the major cell type in skin, have the capacity to synthesize and release potent immunomodulatory cytokines after exposure to irritants. Literature indicates that these pro-inflammatory mediators play an important role in both dermal irritation and irritant contact dermatitis. They are responsible for the skin’s primary response, which consists of edema, erythema and cell infiltration. Currently marketed ELISA assay kits allow the safe, rapid and accurate measurement of several key cytokines. The extent of mediators released from exposed equivalents should be a good indicator of irritation potential. Keratinocyte derived Interleukin-1a (hIL-1α) has an important role in the inflammatory response, being involved in the initiation and maintenance of acute inflammation. In this study, a Modified Draize Rabbit Primary Irritation Test (PDI) was completed for three concentrations of SDS in a cream base (0.3, 1.0 and 3.0 mg/g) and a Placebo (Cream Base only). The results were compared to two in vitro assays in which EPI-100 equivalents were exposed to concentrations of SDS in cream base for one hour, washed thoroughly and maintained for 24 hours. Media was collected after the 24 hour incubation and hIL-1α, GM-CSF, TNF-α and PGE-2 content measured. The hIL-1α release was dose dependent for the level of SDS exposure. Correlation of the in vitro log pg/ml hIL-1α with the in vivo PDI Index were R=0.829 for Trial 1 and R=0.993 for Trial 2. If the two in vitro trials are compared for the same concentrations of SDS, than R=0.854.


Contact Dermatitis, Cutaneous irritancy, Cutaneous irritation, Cutaneous toxicity, Cytokines, Dermal irritancy, Dermal irritancy testing, Dermal irritation, Dermatitis, Contact, Draize prediction model, Draize scores, Draize tests, EPI-100, EpiDerm, IL-1a, Immunomodulatory cytokine genes, Inflammation, Inflammatory, Inflammatory response, Interleukin (IL), Pre-validation, Prediction model, Prevalidation, Skin irritancy, Skin irritation, Skin models, cultured, Sodium dodecyl sulfate (SDS), Validation

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