Metabolism of PCBs

In the rabbit, the nonplanar PCB 2,2, 5,5 -tetrachlorobiphenyl (2,2, 5,5 -TCB) is converted into the 3, 4 -epoxide by monooxygenase attack on the meta-para position, and rearrangement yields two monohydroxymetabolites with substitution in the meta and para positions (Sundstrom et al. 1976). The epoxide is also transformed into a dihydrodiol by epoxide hydrolase attack (see Chapter 2, Section 2.3.2.4). This latter conversion is inhibited by 3,3,3-trichloropropene-l,2-oxide (TCPO), thus providing strong confirmatory evidence for the formation of an unstable epoxide in the primary oxidative attack (Forgue et al. 1980). 

Organic Pollutants An Ecotoxicological Perspective, Second Edition 

P450s of gene family 2 (CYP 2) are more catholic, and can metabolize both planar and nonplanar PCBs. 

Several stndies have related the structures of PCBs to their rates of elimination by mammals. In one stndy (Mizutani et al. 1977), the elimination of tetrachlorobiphenyl 

FIGURE 6.4 Mean concentration of CB153 in pg/g pentane-extractable liquid (PEL) in whole fish from the Dutch Wadden Sea and the cellular fraction of the blood of harbor seals. Numbers of CBs are given in order of elution from the GC column by their systematic numbers according to lUPAC rules as proposed by Ballschmitter and Zell (1980). All concentrations are proportional to the height of the bar. (Reproduced from Boon et al. 1992. With permission.) 

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Wilken A, C Bock, M Bokern, H Harms (1995) Metabolism of PCB congeners in plant cell cultures. Environ Toxicol Chem 14 2017-2022. 

The main organ involved in PCB metabolism and excretion in fish is the liver. Metabolism of PCBs in fish liver homogenates has been demonstrated (29,30,32) and PCB metabolites are excreted into bile (25,28,34). What is not known is extent to which PCB metabolites excreted in bile are eliminated in feces. Also the role of kidneys, gills, intestine and skin in PCB elimination in fish has not been fully elucidated. The only study on urinary excretion of PCBs was in dogfish sharks and revealed that urine was not a major route of elimination (28). 

A comprehensive review of the metabolism of PCBs was published in 1976 by Sundstrom et al. (ref. 139a) confirming the importance of degree of substitution and location of halogens on toxicity. The lesser chlorinated biphenyls are more readily metabolized. The presence of at least two adjacent hydrogens—preferably in positions 3. 4, 5 or 3, 4, 5 —is required for the rapid metabolism of PCBs. This requirement is satisfied by all mono-, di- and trichlorobiphenyls, and by the tetrachlorobiphenyls with the exception of the 3. 3. 5. 5 -chlorinated PCB. This compound was reported particularly toxic to monkeys, and the intermediate formation of chlorinated dibenzofuran was postulated to account for this toxicity (ref. 139c). 

Meanwhile, in laboratory studies the metabolism of PCBs and DDE was also confirmed by detection of their metabolites.63 Based on the many laboratory studies with terrestrial mammals (rodents mainly) and the work mentioned above, it is now believed that biotransformation occurs in three phases ... 

The metabolism of PCBs has been extensively reviewed (Hansen 1999 Hu and Bunce 1999 Safe 1989a, 1993). Differential accumulation and retention of PCBs is related to exposure and the relative biological stability (rate of biotransformation) of each congener. Limited excretion of parent PCBs does occur (see Table 3-7), but biotransformation is necessary for the majority of PCB excretion. 

Significant interspecies differences in the quantitative metabolism of PCBs contributes directly to the species differences in the relative persistence (biological half-life) of PCB congeners. For example, PCB 153 is often the most prevalent PCB detected in humans, due to exposure and the slow rate of biotransformation of this congener. 3-Hydroxy-2,4,5,2 ,4 ,5 -hexaCB was identified as the major metabolite of PCB 153 formed by human CYP2B6 (Ariyoshi et al. 1995). CYP2B6 is constitutively expressed in humans, but only accounts for a maximum of 1-2% of the total CYPs in human liver. 

Substantial attention has been directed (Section 2.5) to the occurrence of sulfonated sulfur-containing metabolites including sulfones and sulfonates. These include both methylsulfonyl derivatives of PCBs and of 2,2 -bis(4-chlorophenyl)-l,l-dichloro-ethene (DDE) (Janak et al. 1998). These are noted further in Section 7.5.2 in the context of the metabolism of PCBs by seals and polar bears. 

R. Hinz and F. Matsumura, Comparative metabolism of PCB isomers by three species of fish and the rat. Bull. Environ. Contam. Toxicol. 18 631 (1977). 

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