SkinEthic (TM) RHE for in vitro evaluation of skin irritation of medical device extracts

摘要

According to ISO 10993 standards for biocompatibility of medical devices, skin irritation is one of the three toxicological endpoints to be always addressed in a biological risk assessment. This work presents a new protocol to assess this endpoint in vitro rather than in vivo. The protocol was adapted to medical devices extracts from the OECD TG 439 with the SkinEthic (TM) RHE model as test system. It was challenged with irritant chemicals, Sodium Dodecyl Sulfate, Lactic Acid and Heptanoic Acid spiked in polar solvents, sodium chloride solution or phosphate buffer saline and non-polar solvent, Sesame Oil. Cell viability measured by MIT reduction after 24 h exposure was used as readout. Quantification of IL-1 alpha release as secondary readout did not increased performance. Samples of heat-pressed polyvinyl chloride (PVC) and silicone sheets infused with or without known irritant (4% Genapol-X80, 6% Genapol-X100 and 15% SDS) were tested after extraction in polar and non-polar solvents. Medical device extracts are classified irritant when the cell viability is inferior or equal to 50%, compared to the negative controls tissues, in at least one extraction solvent. The correct classification of all the samples confirmed the good performance of this new protocol for in vitro skin irritation of medical devices extracts with the SkinEthic (TM) RHE model. Seven naive laboratories were trained in prevision of the Round Robin Study to evaluate Reconstructed Human Epidermis (RhE) models as in vitro skin irritation test for detection of irritant potential in medical device extracts.