H. Seibert et al., AN IN-VITRO TOXICITY TESTING STRATEGY FOR THE CLASSIFICATION AND LABELING OF CHEMICALS ACCORDING TO THEIR POTENTIAL ACUTE LETHAL POTENCY, Toxicology in vitro, 8(4), 1994, pp. 847-850
An in vitro test battery is described which consists of five systems u
sing different types of cells: (1) bovine sperm cells, (2) Balb/c 3T3
cells, (3) primary cultures of rat hepatocytes, (4) primary cultures o
f rat muscle cells, and (5) co-cultures of microcarrier-attached rate
hepatocytes and Balb/c 3T3 cells. This combination of in vitro systems
covers various aspects of cellular toxicity and permits determination
of the intrinsic activity of chemicals with respect to general cytoto
xicity, selective cytotoxicity and interference with selected cell-spe
cific functions (Seibert et al., 1992). During the current phase of ev
aluation the different test systems are used in parallel, resulting in
in vitro toxicity profiles which are the basis (a) for interpretation
with respect to toxic potential, and (b) for the selection of appropr
iate assays for inclusion in a hierarchical approach to testing. Based
on the experience with this test battery, a preliminary stepwise appr
oach is proposed for the classification of chemicals according to thei
r acute lethal potency. The principle steps and candidate tests are: (
1) determination of cytotoxic activity (cytolethal and cytostatic)-spe
rm cells, 3T3 cell line; (2) determination of hepatocyte-specific cyto
toxicity and of the role of bioactivation for cytotoxic activity-cultu
res of hepatocytes and 3T3 cells; and (3) determination of the potenti
al of chemicals to interfere with electrically excitable membranes-mus
cle cell cultures.