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-lipopolysaccharide, was determined for several polychlorinated 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 micrograms/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 = sigma (PCBcongener x TEF)] using the immunotoxicity-derived TEFs (plaque-forming cells/10(6) 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 micrograms/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, 1254, 1248 and 1242, respectively.(ABSTRACT TRUNCATED AT 250 WORDS)
Harper
N
N
Texas A & M University, College Station 77843-4466, USA.
Connor
K
K
Steinberg
M
M
Safe
S
S
D000818:Animals; D000921:Antibody-Producing Cells / Q000187:drug effects / Q000276:immunology; D019363:Cytochrome P-450 CYP1A1; D003577:Cytochrome P-450 Enzyme System / Q000096:biosynthesis; D004305:Dose-Response Relationship, Drug; D005260:Female; D007075:Immunoglobulin M / Q000097:blood; D007166:Immunosuppressive Agents / Q000276:immunology* / Q000633:toxicity*; D008070:Lipopolysaccharides / Q000276:immunology; D051379:Mice; D008862:Microsomes, Liver / Q000187:drug effects / Q000201:enzymology; D010088:Oxidoreductases / Q000096:biosynthesis; D011078:Polychlorinated Biphenyls / Q000819:agonists / Q000037:antagonists & inhibitors / Q000276:immunology / Q000633:toxicity*; D013154:Spleen / Q000187:drug effects / Q000276:immunology
D007075:Immunoglobulin M; D007166:Immunosuppressive Agents; D008070:Lipopolysaccharides; C048761:trinitrophenyl-lipopolysaccharide; D003577:Cytochrome P-450 Enzyme System; D011078:Polychlorinated Biphenyls; D010088:Oxidoreductases; D019363:Cytochrome P-450 CYP1A1