Acute cytotoxicity of ten chemicals in human and rat cultured hepatocytes and in cell lines: Correlation between in vitro data and human lethal concentrations.
The cytotoxicity of ten chemicals from the MEIC list (nos 11-20) was evaluated in human and rat cultured hepatocytes and in two established cell lines (HepG2 and 3T3) according to the Multicentre Evaluation of In Vitro Cytotoxicity programme organized by the Scandinavian Society of Cell Toxicology. The lactate dehydrogenase intracellular activity and the MTT test were used as endpoints of cytotoxicity after 24 hr of exposure to the chemicals. Sodium chloride and lithium sulphate were the least cytotoxic compounds in all of the cellular systems (IC(50), 25-150 mm). The eight remaining chemicals (1,1,1-trichloroethane, phenol, sodium fluoride, malathion, 2,4-dichlorophenoxyacetic acid, xylene, nicotine and potassium cyanide) showed a similar cytotoxic potential in the four in vitro systems in a narrow range of concentrations (IC(50), 1-30 mm). The data suggest that these ten chemicals have a basal cytotoxic effect common to the four in vitro systems, and probably none of these compounds could be considered either hepatotoxic or to exert species-specific toxicity. The correlation between in vitro data and human lethal blood concentrations showed a relatively low predictability for the toxicity of six compounds with important lethal effects on the CNS. The predictability of the in vitro systems was similar to that of in vivo rodent tests (LD(50)) only when low cytotoxic concentrations (IC(10)) were used for the correlation.
Jover
R
R
Unidad de Hepatología Experimental, Centro de Investigación, Hospital Universitario "La Fe", SVS Avda Campanar 21, E-46009 Valencia, Spain.
Ponsoda
X
X
Castell
J V
JV
Gómez-Lechón
M J
MJ