Metabolism and metabolites of polychlorinated biphenyls

Abstract

Abstract The metabolism of polychlorinated biphenyls (PCBs) is complex and has an impact on toxicity, and thereby on the assessment of PCB risks. A large number of reactive and stable metabolites are formed in the processes of biotransformation in biota in general, and in humans in particular. The aim of this document is to provide an overview of PCB metabolism, and to identify the metabolites of concern and their occurrence. Emphasis is given to mammalian metabolism of PCBs and their hydroxyl, methylsulfonyl, and sulfated metabolites, especially those that persist in human blood. Potential intracellular targets and health risks are also discussed.

Keywords: PCB methyl sulfones; PCB sulfates; human exposure; hydroxylated PCBs; polychlorobiphenylols; reactive intermediates.

Figure 1

General metabolic scheme for a representative lower-chlorinated PCB congener, PCB 3. Enzymes involved in the metabolism are indicated by the letters A, B and D-N with the letter C indicating non-enzymatic transformations. Enzymes suggested for these transformations are listed as follows: A, Cytochrome P-450 (CYP) enzyme system, Direct insertion in meta position; CYP2B (rodents); B, Cytochrome P-450 enzyme system; CYB2B1 (rodents); CYP3A4 (humans); Non-coplanar PCBs: CYB2B, 2C, 3A ; C, Non-enzymatic reaction; D, Glutathione S-transferase; E, Epoxide hydrolase; F, Dihydrodiol dehydrogenase (AKR1C); G, Autooxidation and/or Peroxidases; H, γ–Glutamyl transpeptidase, then cysteinylglycine dipeptidase; I, Cysteine S-conjugate β-lyase; J, Thiol S-methyltransferase; K, CYP and/or FAD-containing monooxygenases (FMO); L, UDP-glucuronosyl transferase (UGT); M, Sulfotransferase (SULT); N, Cysteine S-conjugate N-acetyltransferase

Figure 2

Chemical structures of the most common OH-PCB congeners present in human blood (c.f. Table 2). The full names of the five OH-PCBs are: 2,3,3’,4’,5-pentachloro-4-biphenylol (4-OH-PCB 107); 2,2’,3’,4,4’,5- hexachloro-3-biphenylol (3’-OH-PCB 138); 2,2’,3,4’,5,5’- hexachloro-4-biphenylol (4-OH-PCB 146); 2,2’,4,4’,5,5’- hexachloro-3-biphenylol (3-OH-PCB 153) and 2,2’,3,4’,5,5’,6 - heptachloro-4-biphenylol (4-OH-PCB 187).