AQUA seminar: Mis‘B’having – Comparing and contrasting the bioaccumulation behaviour of PCBs and their hydroxylated metabolites (OH-PCBs)

James Armitage, University of Toronto, Canada.

It is well established that neutral hydrophobic organic contaminants such as polychlorinated biphenyls (PCBs) exhibit the highest wet weight concentrations in adipose tissue followed by other tissues with relatively high total lipid content.  Recent biomonitoring studies have also shown that hydroxylated PCB metabolites (i.e., OH-PCBs) exhibit a different internal tissue distribution with higher wet weight concentrations in blood and liver compared to adipose.  While interactions with plasma proteins may be a factor explaining these observations, another key consideration is that OH-PCBs are ionogenic (i.e., dissociate in vivo and hence are present in a neutral and charged form).  The physical-chemical properties of hexachlorobenzene (HCB, neutral organic) and pentachlorophenol (PCP, weak acid, pKa ~ 4.7) provide a useful analogy when considering PCBs and OH-PCBs.  Here we apply a recently developed Physiologically-Based Pharmacokinetic model (PBPK) for ionogenic organic chemicals (IOCs) to simultaneously model the accumulation and internal tissue distribution of a set of PCBs and their OH-metabolites.  The model distinguishes between neutral (storage) lipids, zwitterionic (neutral) phospholipids, plasma proteins and other non-lipid organic matter (NLOM).    As there is a relationship between degree of chlorination and estimated pKa (as # of chlorines ↑, pKa ↓, degree of ionization at pH 7.4 ↑), it is important to recognize that all OH-PCBs do not distribute internally in the same manner.  Besides whole blood, OH-PCBs exhibiting a high degree of ionization (i.e., predominantly charged in vivo) tend to favour tissues with elevated phospholipid content such as the liver whereas OH-PCBs exhibiting a low degree of ionization (i.e., predominantly neutral) behave like the parent compound (and hence exhibit the highest wet weight concentrations in adipose tissue). Assumptions regarding biotransformation (Phase I and II processing) are also influential.  While the current model application is focused on PCBs and OH-PCBs, the findings have implications for the distribution of the hydroxylated metabolites of other POPs such as OH-PBDEs (i.e., biotransformation products of polybrominated diphenyl ethers).


Key Words:  Bioaccumulation, hydroxylated PCBs, pKa, internal tissue distribution

Published Aug. 31, 2015 9:17 AM - Last modified Nov. 1, 2016 9:31 PM