Immunosuppressive Activity of Polychlorinated Biphenyl Mixtures and Congeners: Nonadditive (Antagonistic) Interactions

Toxic equivalency factors (TEFs) for PCBs, PCDDs, PCDFs for humans and wildlife.

“…Based on studies with chicken embryos, it has been concluded that birds can be highly responsive toward non-ortho PCBs, although much of the information available concerns induction of CYPlAI and not distinct toxic (118) New data support the original value (91,96,108); no revision is recommended. 0.0001 0.0001 2',3,4,4',5-PentaCB (123) No new data are available; no revision is recommended.…”

“…In general, the TEF/TEQ approach using CYP1A induction accurately predicted dioxin equivalents within a complex mixture when compared to gas chromatography-mass spectrometry analysis or in vivo assessments, but may overestimate the TEQs when using other responses such as PFC (91). The accuracy of this in vitro approach also depends on the composition of the sample.…”

“…Furthermore, these in vitro studies have shown that some responses (i.e., PFC, reporter gene, and AHH/EROD induction) and cell lines (H4ILE, recombinant reporter cells) are susceptible to nonadditive interactions. This is especially true if the complex mixture contains PCB congeners that are partial Ah receptor agonists (91,142,178,179 (11,129,180). In addition, structure-activity relationships have also been determined for effects that are not directly related to the Ah receptor and involve both parent compounds and their hydroxylated metabolites.…”

“…Recendy, these nonadditive interactions of PCB on dioxinlike effects have been reviewed (193). In summary, the following antagonistic effects ofnondioxinlike PCBs were described: induction of EROD activity in chick embryo hepatocytes (194), splenic PFC response to sheep erythrocytes in mice (195), splenic PFC response to trinitrophenyl-lipopolysaccharide in mice (196), serum IgM units in mice (91), mouse fetal deft palate (110,195), and chick embryo malformations and edema and liver lesions (197). The apparent antagonism by PCB 153 of the TCDD-induced immunosupression is due to the enhanced immune response induced by PCB 153 (198).…”

Inhibition of 3,3′,4,4′,5-Pentachlorobiphenyl-Induced Chicken Embryotoxicity by 2,2′,4,4′,5,5′-Hexachlorobiphenyl

“…However, the results obtained for complex and simple (binary) mixtures of PCBs indicate that there are species-and response-specific additive (Eadon et al, 1986;Van der Kolk et al, 1992;De Jongh et al, 1992, 1993aSilkworth et al, 1993) and nonadditive (primarily antagonistic) (Bannister et al, 1987;Haake et al, 1987;Biegel et al, 1989;Safe, 1989, 1990;Morrissey et al, 1992;Harper et al, 1995) interactions. For example, the induction of CYPlAl-dependent hepatic microsomal enzyme activities by commercial Aroclor mixtures in the rat were essentially additive contributions from the individual Ah receptor agonists in the mixture (Harris et al, 1993).…”