CYTOTOXICITY, MUTAGENICITY, AND IMMUNOTOXICITY

The general principles and standard methods for cytotoxicity, mutageni city, and immunotoxicity testing in vitro are described. Exceptional a nd ordinary results in the published literature are reviewed with spec ial emphasis on blood-material interactions. This chapter emphasizes i nteractions in the blood path, although it is recognized that any devi ce that has contact with internal organs or tissues has contact either directly or indirectly with the blood path. Advances have been made i n the evaluation of devices and materials for cytotoxicity and genotox icity. The principal methods for cytotoxicity, i.e., direct contact, e xtract dilution, and agar diffusion assays, have been employed extensi vely throughout industry, government, and academia. They have been dev eloped into standard methods in developed countries and by internation al organizations. Future directions will entail refinement of these as says, newer automated methods, and improvements in the understanding a nd hazard assessment of target cell toxicity. Genotoxicity tests, incl uding mutagenicity and clastogenicity, have had widespread application s in testing pure chemicals. Although the methods have been developed into international standards, there are many deviations and uncertaint ies in the applications of these standards and the interpretation of d ata. In particular, there is considerable confusion about the use of t hese methods for complex mixtures including the extractables from medi cal devices. There is no convincing evidence that long-term human clin ical use of bioprosthetic or prosthetic devices has resulted in irreve rsible genotoxic effects. In vitro immunotoxicity testing has been pri marily limited to phagocytosis and complement testing. Assays for hype rsensitivity and cell killing have been developed but not exploited.