Coleman1, K.P., Casas1, J.W., Lewerenz1, G.M., Rankin1, E.A., Willoughby2, J.A. Sr., Blakeman2, L.C. and McKim2, J.M. Jr. 1Medtonic, Inc., Minneapolis, MN, 55432 2CeeTox, Inc., Kalamazoo, MI, 49008

In accordance with ISO 10993, the rabbit skin irritation test is used to assess medical device biocompatibility, however, this method is time-consuming and expensive.  Our study’s goal was to determine if the EpiDerm™ reconstructed human skin model (MatTek Corp.) could be an acceptable alternative. To that end, eleven medical device polymers and adhesives were selected for testing.  Four extracts were prepared of each test article, two each with saline and sesame oil as vehicles, resulting in 44 total matrices.  Half of the extracts were spiked with known amounts of two R-38 dermal irritants (lactic and heptanoic acid).  A range-finding study determined the lowest spiking concentrations that would produce skin irritation (LOAEL).  Tissues were exposed for 24 hours.  Cell viability was assessed by MTT and IL-1α release was measured by ELISA.  The positive control (5% SDS) reduced cell viability to 8.5% of the negative control (PBS) and increased the release of IL-1α (>500 pg/ml) into the culture medium.  Cells exposed to unspiked saline and sesame oil extracts exhibited cell viabilities >90% relative to the negative control.  IL-1α released from cells exposed to saline extracts (19.6 pg/ml – 99.7 pg/ml) or to sesame oil extracts (91.8 pg/ml – 176.4 pg/ml) was considerably less than the positive control.  Cells exposed to saline extracts spiked with 3.25% lactic acid exhibited significantly reduced mean cell viabilities (12.6% – 17.2%).  Cells exposed to sesame oil extracts spiked with 1.25% heptanoic acid also exhibited reduced mean cell viabilities (25.5% – 41.7%).  The spiked exposure groups released substantial amounts of IL-1α (253.5 pg/ml – 387.4 pg/ml) signifying severe skin irritation. Our results indicate that the EpiDerm™ model can detect the presence of strong skin irritants at low concentrations in medical device extract mixtures.  Therefore, this model may be a suitable replacement for the rabbit skin irritation test to evaluate medical device biocompatibility.


Adhesives, Biocompatibility, EPI-200, EpiDerm™, Extracts, IL-1α release, ISO 10993, Medical device, Medical device extract, Polymers, R-38 irritant, Rabbit Draize test, Rabbit skin irritation test

Materials Tested

Ethylene tetrafluoroethylene, Heptanoic acid, Lactic acid, Liquid silicone rubber, Phthalate-free PVC, Polyether ether ketone, Polycarbonate, Polycarbonate-urethane, Polyurethane elastomer, Saline, Sesame oil, Silicone polyether urethane, Silicone rubber adhesive

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