IN VITRO HUMAN SKIN IRRITATION TEST FOR EVALUATION OF MEDICAL DEVICE EXTRACTS.
- TR Number: 761
- Authors: J.W. Casas a, G.M. Lewerenz a, E.A. Rankin a, J.A. Willoughby Sr. b,1, L.C. Blakeman b,1, J.M. McKim Jr. b,1, K.P. Coleman a, a Medtronic, Inc., 11520 Yellow Pine St. N. W., C202, Minneapolis, MN 55448, USA b CeeTox, Inc., 4717 Campus Drive, Kalamazoo, MI 49008, USA
- Materials Tested: Ethylene tetrafluoroethylene, heptanoic acid, lactic acid, Liquid silicone rubber, Phthalate-free PVC, Polycarbonate, Polycarbonate–urethane, Polyether ether ketone, Polyurethane elastomer,sesame oil, Silicone polyether urethane, Silicone rubber adhesive
Purpose: The aim of this study was to determine if the EpiDerm™ reconstructed human skin model (Mattek Corp.) could be an acceptable alternative to the ISO 10993-required rabbit skin irritation test for assessing medical device biocompatibility. Eleven medical device polymers were tested. Four extracts were prepared per polymer, two each with saline and sesame oil; half were spiked with two R-38 irritants, lactic acid for saline extracts and heptanoic acid for the sesame oil extracts. Tissue viability was assessed by MTT reduction and the proinflammatory response was assessed by IL-1α release. LOAELs of 2% for lactic acid in saline and 0.7% for heptanoic acid in sesame oil were determined. A cell viability reduction of >50% was indicative of skin irritation. Cells exposed to saline extracts spiked with 3.25% lactic acid had 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%). All spiked cells released substantial amounts of IL-1α (253.5–387.4 pg/ml) signifying a proinflammatory response. These results indicate that the EpiDerm™ model may be a suitable in vitro replacement for the assessment of the irritation potential of medical device extracts.