Sources and toxicities of phenolic polychlorinated biphenyls (OH-PCBs)

Abstract

Polychlorinated biphenyls (PCBs), a group of 209 congeners that differ in the number and position of chlorines on the biphenyl ring, are anthropogenic chemicals that belong to the persistent organic pollutants (POPs). For many years, PCBs have been a topic of interest because of their biomagnification in the food chain and their environmental persistence. PCBs with fewer chlorine atoms, however, are less persistent and more susceptible to metabolic attack, giving rise to chemicals characterized by the addition of one or more hydroxyl groups to the chlorinated biphenyl skeleton, collectively known as hydroxylated PCBs (OH-PCBs). In animals and plants, this biotransformation of PCBs to OH-PCBs is primarily carried out by cytochrome P-450-dependent monooxygenases. One of the reasons for infrequent detection of lower chlorinated PCBs in serum and other biological matrices is their shorter half-lives, and their metabolic transformation, resulting in OH-PCBs or their conjugates, such as sulfates and glucuronides, or macromolecule adducts. Recent biomonitoring studies have reported the presence of OH-PCBs in human serum. The occurrence of OH-PCBs, the size of this group (there are 837 mono-hydroxyl PCBs alone), and their wide spectra of physical characteristics (pKa's and log P's ranging over 5 to 6 orders of magnitude) give rise to a multiplicity of biological effects. Among those are bioactivation to electrophilic metabolites that can form covalent adducts with DNA and other macromolecules, interference with hormonal signaling, inhibition of enzymes that regulate cellular concentrations of active hormones, and interference with the transport of hormones. This new information creates an urgent need for a new perspective on these often overlooked metabolites.

Keywords: Biotransformation; Endocrine disruption; Hydroxylated PCBs; Metabolites; PCBs; Persistent organic pollutants; Phenolic PCBs.

Figure 1. Change in pKa and Log P vs. Chlorine number of hydroxylated polychlorinated biphenyls (PCBs)

Mean pKa and mean Log P values of mono-hydroxyl PCBs were calculated from data provided for each group (please see reference Grimm et al 2015b)

Figure 2. Metabolism of hydroxylated PCBs

The parent PCBs are oxidized in reactions catalyzed by cytochrome P-450 mono-oxygenases (CYPs) to form hydroxylated PCBs. The hydroxylated PCBs may then be conjugated to form PCB sulfates or PCB glucuronides, or metabolized into reactive semi-quinones or quinones.

Figure 3

The atropisomer of 5-OH PCB 136 eluting second on the Chirasil-Dex column (E₂-5-OH-PCB 136) and the atropisomer of 4-OH PCB 136 eluting first on the Cyclosil-B column (E₁-4-OH-PCB) are formed preferentially in incubations of racemic PCB 136 with liver microsomes from rats pretreated with different inducers of cytochrome P-450 enzymes. Based on incubations with pure PCB 136 atropisomers, the first and second eluting atropisomer of both 5-OH-PCB 136 and 4-OH-PCB 136 are formed from (−)-PCB 136 and (+)-PCB 136, respectively. Enantioselective gas chromatograms of (A) racemic 5-OH-PCB 136 and 4-OH-PCB 136 standards; (B) E₁-5-OH-PCB 136 and E₁-4-OH-PCB 136 formed from (−)-PCB 136; (C) E₂-5-OH-PCB 136 and E₂-4-OH-PCB 136 formed from (+)-PCB 136; and chiral signature of 5-OH-PCB 136 and 4-OH-PCB 136 formed by liver microsomes from rats treated with (D) PB, (E) DEX or (F) VEH. All OH-PCB metabolites were methylated with diazomethane prior to GC analysis. Reprinted with permission from (Wu et al. 2011a). Copyright 2011 American Chemical Society.