Coplanar PCBs

Figure 2 illustrates the two primary classes of PCBs that exhibit this type of activity, namely the coplanar PCBs and their monoortho coplanar analogues. 

Details of some inducible P450 forms that play key roles in the metabolism of xenobiotics are shown in Table 2.4. P450s belonging to family lA are induced by various lipophilic planar compounds including PAHs, coplanar PCBs, TCDD and other dioxins, and beta naphthoflavone (Monod 1997). As noted earlier, such planar compounds are also substrates for P450 lA. In many cases, the compounds induce the enzymes that will catalyze their own metabolism. Exceptions are refractory compounds such as 2,3,7,8-TCDD, which is a powerful inducer for P450 lA but a poor substrate. 

In the examples given, there is good evidence for the formation of an unstable epoxide intermediate in the production of monohydroxymetabolites. However, there is an ongoing debate about the possible operation of other mechanisms of primary oxidative attack that do not involve epoxide formation, for example, in the production of 2 OH 3,3, 4,4 -TCB (Figure 6.3). As mentioned earlier, P450s of gene family 1 (CYP 1) tend to be specific for planar substrates, including coplanar PCBs they do not appear to be involved in the metabolism of nonplanar PCBs. On the other hand. 

Ah-receptor-mediated toxicity is particularly associated with the highly toxic compound 2,3,7,8-tetrachloro-dibenzo-p-dioxin (TCDD), commonly referred to as dioxin. TCDD, and the concept of toxicity equivalency factors (TEFs) based on TCDDs, will be dealt with in Chapter 7. The main point to make at this juncture is that the toxicity of each individual coplanar congener in a mixture can be expressed in terms of a toxic equivalent calculated relative to the toxicity of dioxin. Summation of the toxic equivalents of the individual coplanar PCBs gives a measure of the toxicity of the whole mixture, as expressed through the Ah receptor mechanism. 

The toxicology of PCBs is complex and not fully understood. Coplanar PCBs interact with the Ah-receptor, with consequent induction of cytochrome P4501A1/2 and Ah-receptor-mediated toxicity. Induction of P4501A1 provides the basis of valuable biomarker assays, including bioassays such as CALUX. Certain PCBs, for example, 3,3, 4,4 -TCB, are converted to monohydroxymetabolites, which act as thyroxine antagonists. PCBs can also cause immunotoxicity (e.g., in seals). 

PCDDs and PCDEs, together with coplanar PCBs, can express Ah-receptor-mediated toxicity. TCDD (dioxin) is used as a reference compound in the determination of TEFs, which can be used to estimate TEQs (toxic equivalents) for residues of PHAHs found in wildlife samples. Biomarker assays for Ah-receptor-mediated toxicity have been based on the induction of P450 lAl. TEQs measured in field samples have sometimes been related to toxic effects upon individuals and associated ecological effects (e.g., reproductive success). 

Induction of P450 lAl/2 provides the basis for biomarker assays for PAHs and other planar organic pollutants, such as coplanar PCBs, PCDDs, and PCDFs. 

Some hydroxy metabolites of coplanar PCBs, such as 4-OH and 3,3 4,5 -tet-rachlorobiphenyl, act as antagonists of thyroxin (Chapter 6, Section 6.2.4). They have high affinity for the thyroxin-binding site on transthyretin (TTR) in plasma. Toxic effects include vitamin A deficiency. Biomarker assays for this toxic mechanism include percentage of thyroxin-binding sites to which rodenticide is bound, plasma levels of thyroxin, and plasma levels of vitamin A. 

Coplanar PCBs, PCDDs, and PCDFs express Ah-receptor-mediated toxicity (Chapter 6, Section 6.2.4). Binding to the receptor leads to induction of cytochrome P4501 and a number of associated toxic effects. Again, toxic effects are related to the extent of binding to this receptor and appear to be additive, even with complex mixtures of planar polychlorinated compounds. Induction of P4501A1/2 has been widely used as the basis of a biomarker assay. Residue data can be used to estimate TEQs for dioxin (see Chapter 7, Section 7.2.4). 

Ah receptor (Aryl hydrocarbon receptor) A receptor located on a cytoplasmic protein to which planar componnds snch as PAHs, coplanar PCBs, and PCDDs bind. Binding initiates the indnction of cytochrome P4501A1/2. 

Ah-receptor-mediated toxicity Toxic effects associated with the binding of polychlorinated aromatic componnds snch as coplanar PCBs and PCDDs to the Ah receptor. 

Kuehl, D.W., R. Haebler, and C. Potter. 1994. Coplanar PCB and metal residues in dolphins from the U.S. Atlantic coast including Atlantic bottlenose obtained during the 1987/88 mass mortality. Chemosphere 28 1245-1253. 

Bosveld, B.A.T.C., M. van den Berg, and R.M.C. Theelen. 1992. Assessment of the EROD inducing potency of eleven 2,3,7,8-substituted PCDD/Fs and three coplanar PCBs in the chick embryo. Chemosphere 25 911-916. 

Hong, C.S. and B. Bush. 1990. Determination of mono- and non-ortho coplanar PCBs in fish. Chemosphere 21 173-181. 

Hong, C.S., B. Bush, and J. Xiao. 1992. Coplanar PCBs in fish and mussels from marine and estuarine waters of New York State. Ecotoxicol. Environ. Safety 23 118-131. 

Janz, D.M. and C.D. Metcalfe. 1991a. Relative induction of aryl hydrocarbon hydroxylase by 2,3,7,8-TCDD and two coplanar PCBs in rainbow trout (Oncorhynchus mykiss). Environ. Toxicol. Chem. 10 917-923. 

Kannan, N., S. Tanabe, T. Wakimoto, and R. Tatsukawa. 1987a.Coplanar PCBs in Aroclor and Kaneclor mixtures. Jour. Assoc. Anal. Chem. 70 451-454. 

Tanabe, S., N. Kannan, M. Ono, and R. Tatsukawa. 1989. Toxic threat to marine mammals increasing toxic potential of non-ortho and mono-ortho coplanar PCBs from land to ocean. Chemosphere 18 485-490. 

Tarhanen, J., J. Koistinen, J. Paasivirta, P.J. Vuorinen, J. Koivusaari, I. Nuuja, N. Kannan, and R. Tatsukawa. 1989. Toxic significance of planar aromatic compounds in Baltic ecosystem — new studies on extremely toxic coplanar PCBs. Chemosphere 18 1067-1077. 

White, D.H. and J.W. Hardy. 1994. Ambient air concentrations of PCDD s, PCDF s, coplanar PCBs, and PAHs at the Mississippi sandhill crane national wildlife refuge, Jackson County, Mississippi. Environ. Monitor. Assess. 33 247-256. 

Nakata, H. et al., Evaluation of mitogen-induced responses in marine mammal and human lymphocytes by in-vitro exposure of butyltins and non-ortho coplanar PCBs, Environ. Pollut., 120, 245, 2002. 

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