CORRELATION OF SYNERGISTIC CYTOTOXIC EFFECTS OF ENVIRONMENTAL CHEMICALS IN HUMAN FIBROBLASTS WITH THEIR LIPOPHILICITY

The cytotoxic combination effects of 2,4-D with 12 xenobiotics having different lipophilicity were investigated in human fibroblasts at thei r no effect concentrations (NOEC). Each of the chemicals tested in bin ary combinations enhanced the toxicity of 2,4-D. These synergistic com bination effects were independent of the chemical structure of the tes t compounds. However, the NOEC's of the xenobiotics used in the combin ations varied by a factor of 10 000. For strongly lipophilic compounds the lowest NOEC's were needed to induce synergistic cytotoxicity. A l inear regression analysis of the concentrations (NOEC's) of the 12 com bined xenobiotics against their lipophilicity revealed a correlation w ith r = 0.96 for 11 agents. This close correlation may be explained by the membrane damaging properties of lipophilic compounds which enhanc e the uptake of hydrophilic agents.