Immunosuppressive Activity of Polychiorinated Biphenyl Mixtures and Congeners: Nonadditive (Antagonistic) Interactions
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abstract
The dose-response inhibition of the splenic plaque-forming cell (PFC) response and serum IgM units to the antigen, trinitrophenyl-lipopolysaccharide, was determined for several polychiorinated biphenyl (PCB) mixtures and congeners in female B3C3F1 mice. The ED50 values for Aroclor 1260-, 1254-, 1248-, and 1242-induced immunotoxicity varied by less than twofold from 355 to 699 mg/kg. The range of ED50 values for 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD), 3,3 ,4,4-tetrachlorobiphenyl, 3,3 ,4,4,5-pentaCB, 3,3,4,4,5,5-hexaCB, 2,3,3,4,4-pentaCB, 2,3,4,4,5-pentaCB, 2,3,3,4,4,5-hexaCB, 2,3,3,4,4,5,5-heptaCB, 2,2,3,3,4,4,5-heptaCB, and 2,2,3,4,4,5,5-heptaCB were 4.6 to 4.9, 134 to 245, 4.7 to 7.0, 6.9 to 11.1, 88,000 to 121,000, 122,000 to 132,000, 99,000 to 157,000, 89,000 to 129,000, 117,000 to 240,000, and 132,000 to 238,000 g/kg, respectively. The immunotoxicity-derived toxic equivalency factors (TEFs) for these congeners could be calculated from the ED50 (TCDD)/ED50 (congener) ratios and the TEF values were within the range of those previously determined for other aryl hydrocarbon receptor-mediated responses. Based on the known concentrations of these congeners in the PCB mixtures, TCDD or toxic equivalents (TEQs) in the mixture were calculated [i.e., TEQ = (PCBcongener TEF)] using the immunotoxicity-derived TEFs (plaque-forming cells/106 viable cells). TEQ values for Aroclors 1260, 1254, 1248, and 1242 were 16.0, 54.4, 260.4, and 197 ppm, respectively. Based on the ED50 value for the immunosuppressive activity of TCDD (4.8 g/kg), the calculated ED50 values for immune suppression by Arodors 1260, 1254, 1248, and 1242 were 300, 88, 18, and 24 mg/kg, respectively. The ED50 (observed)/ED50 (calculated) ratios were 1.2, 5.9, 21, and 22.0 for Aroclors 1260, 1254, 1248 and 1242, respectively. Thus, for Aroclors 1254, 1248, and 1242, the high ED50 (observed)/ED50 (calculated) ratios (i.e., 5.9 to 22.0) indicate that the TEF approach overestimates the toxicity of these mixtures due to non-additive (antagonistic) interactions of the PCBs. In contrast, the TEF approach was useful in determining the immunotoxicity of the Aroclor 1260 mixture. 1995 by the Society of Toxicology.
