Human Cell Culture Toxicity Testing of Medical Devices and Correlation to Animal Tests

Abstract

WI-38 cells were used as indicators of toxicity in comparison to in vivo animal tests. Cell culture tests included 1) elution with cell culture medium, 2) direct contact with an agarose overlay, 3) elution with saline on an agarose overlay, and 4) elution with cottonseed oil on an agarose overlay. Animal tests performed were 1) systemic injection tests in mice, 2) intracutaneous tests in rabbits, and 3) intramuscular implantation in rabbits. Materials tested included rubber, polypropylene, polyvinyl chloride, copolymers, paper, polyethylene, and silicone rubber. WI-38 cell testing, by elution with cell culture medium, was the most sensitive indicator of toxicity followed in descending order by the intracutaneous rabbit test and the direct contact (agarose overlay) cell culture test. The other tests proved relatively insensitive measures of toxicity. Positive results were obtained with rubber, polyvinyl chloride, copolymers, and paper. The degree of correlation between in vitro and in vivo tests was rubber 86%, polypropylene 100%, and polyvinyl chloride 67%.

Ethylene oxide and associated reaction products, 2-chloro-etnanol and ethylene glycol, were considered potential toxic components of gas sterilized materials and were toxicity tested in WI-38 cells. Cell culture detection limits were ethylene oxide 25 ppm, 2-chloroethanol 1000 ppm, and ethylene glycol 100,000 ppm.