IMMUNOSUPPRESSIVE ACTIVITY OF POLYCHLORINATED BIPHENYL MIXTURES AND CONGENERS - NONADDITIVE (ANTAGONISTIC) INTERACTIONS

The dose-response inhibition of the splenic plaque-forming cell (PFC) response and serum IgM units to the antigen, trinitrophenyl-lipopolysa ccharide, was determined for several polychlorinated biphenyl (PCB) mi xtures and congeners in female B3C3F1 mice. The ED50 values for Aroclo r 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 132,00 0 to 238,000 mu g/kg, respectively. The immunotoxicity-derived toxic e quivalency 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 r eceptor-mediated responses. Based on the known concentrations of these congeners in the PCB mixtures, TCDD or toxic equivalents (TEQs) in th e mixture were calculated [i.e., TEQ = Sigma (PCBcongener X TEF)] usin g the immunotoxicity-derived TEFs (plaque-forming cells/10(6) viable c ells). TEQ values for Aroclors 1260, 1254, 1248, and 1242 were 16.0, 5 4.4, 260.4, and 197 ppm, respectively. Based on the ED50 value for the immunosuppressive activity of TCDD (4.8 mu g/kg), the calculated ED50 values for immune suppression by Aroclors 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, 12 54, 1248 and 1242, respectively. Thus, for Aroclors 1254, 1248, and 12 42, 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 nonadditive (antagonistic) interactions of the PCBs. In contrast, the TEF approach was useful in determining the immunotoxi city of the Aroclor 1260 mixture. (C) 1999 Society of Toxicology