Subacute cytotoxicity testing with cultured human lung cells

This study was designed to evaluate the potential of an in vitro cell culture method for its ability to determine subacute cytotoxicity and to compare the cytotoxic concentrations with rodent LD(50)s and clinical human toxicity data. Human fetal lung fibroblasts (HFL1) were incubated in the absence or presence of increasing concentrations of test chemicals for 72 h, and cell proliferation was used as a marker for toxicity. Inhibitory concentrations were extrapolated from concentration-effect curves after linear regression analysis. Comparison of the cytotoxicity data from testing 50 chemicals, with available human lethal concentrations for the same chemicals, revealed that the 72-h experimental IC(50)s are as accurate predictors of human toxicity as equivalent toxic blood concentrations derived from rodent LD(50)s. In addition, our results demonstrate that subacute 72-h exposure of HFL1 cells more accurately predicts cytotoxicity than a 24-h mitochondrial assay previously conducted in our laboratory, although the experimental IC(50) values were not statistically different in the two assays. It is anticipated that this procedure, together with a related battery of tests, may supplement or replace currently used animal protocols to screen chemicals for human risk assessment.