D. Hopkinson et al., INVITRO CYTOTOXICITY TESTING - 24-HOUR AND 72-HOUR STUDIES WITH CULTURED LUNG-CELLS, ATLA. Alternatives to laboratory animals, 21(2), 1993, pp. 167-172
This study was designed to evaluate the potential of an in vitro cell
culture method for its ability to determine cytotoxicity and to compar
e the cytotoxic concentrations with established LD50 values for the sa
me chemicals. Rat lung epithelial cells (L2) were incubated in the abs
ence or presence of increasing concentrations of the test chemical for
24 hours, and the inhibition of incorporation of radio-labelled amino
acids into newly synthesised proteins was used as a marker for toxici
ty. In addition, cultured cells were exposed to the test chemicals for
72 hours, and cell proliferation experiments were performed as parall
el measures of toxicity. Inhibitory concentrations were extrapolated f
rom concentration-effect curves after linear regression analysis. The
biological significance of the results of testing 20 chemicals shows t
hat the experimental IC50 values are as accurate as predictors of huma
n toxicity as are equivalent toxic blood concentrations derived from r
odent LD50s. Results obtained from 72-hour growth studies reveal a gre
ater sensitivity to cytotoxicity than from the 24-hour protein synthes
is experiments. Statistically, however, the differences between the tw
o protocols are inconclusive. It is anticipated that these procedures,
together with a related battery of tests, may supplement or replace a
nimal protocols currently used for human risk assessment.