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.