In vitro human skin irritation test for evaluation of medical device extracts

•Extracts of medical device materials were tested for skin irritation potential.•These extracts were spiked with the skin irritants lactic acid and heptanoic acid.•Cell viability was measured with MTT and IL-1α in a reconstructed human epidermal (RhE) assay.•Results indicate that the RhE assay was able to detect skin irritants in dilute medical device material extracts.•Consequently, the RhE assays may be suitable replacements for the rabbit skin irritation test.

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.