Use of the CaCo-2 model in the screening of polluting substance toxicity

The aim of this work was to investigate the oral toxicity of representative chemicals chosen from each class of the list of 132 substances present in industrial effluents after the EEC Directive 76-464. Owing to its character ization as a model of the intestinal epithelium, the CaCo-2 cell line model was chosen. Cytotoxicity was assayed using the tetrazolium blue (MTT) test . For most of the substances, a linear correlation was observed between the octanol;water partition coefficient (log Kw) and the median inhibition con centration (IC50) This relationship between lipophilicity and toxicity is t he hallmark of a narcotic mechanism of action. However, diethylamine appear ed more toxic than the correlation would predict. Other amines were then te sted (tert-butylamine, n-butylamine and benzylamine). All of these did not fit into the baseline correlation. The IC50 were corrected by taking into a ccount only thr non-ionized, lipid insoluble, concentration at pH 7.3. The amines still did not fit into the correlation, reinforcing the idea of a no n-narcotic mechanism. The toxicity of a large number of substances can thus be predicted from their physico-chemical properties only when the substanc es exert a direct and non-specific effect. The amines appeared more toxic t han substances with the same partition coefficient, showing that knowledge of the only lipophilicity is too restrictive to predict toxicity. (C) 1999 Elsevier Science Ltd. All rights reserved.