Health News

New insight into how long-banned chemicals (PCBs) unleash their toxicity inside the body

Polychlorinated biphenyls (PCBs) (*1) were widely used in industrial and commercial products including plastics, paints, electronic equipment and insulating fluids. Their manufacture was extensively banned from the late 70s onwards due to their toxicity, however large amounts still remain in our environment and accumulate inside animals’ bodies.

Chiral PCBs (*2) are PCBs that have two mirror-image isomers (*3); these isomers are identical reflections of each other with the same composition. Chiral PCBs are particularly dangerous because they have more chlorine atoms, which are hard for the body to break down, so they can accumulate in the body easily and their isomers are metabolized differently, causing isomer-specific toxicity (particularly neurodevelopmental issues). However, the process behind this selective metabolism was not known. To address this, a research group has illuminated how enzymes produced by the body unevenly metabolize the mirror-image isomers. These results will make it possible to estimate PCB metabolism and detoxification pathways in animals. They will also contribute towards the development of technology to make predictions about chiral PCBs’ mirror isomers, so that we can obtain a better understanding of potential toxicity in humans and other mammals.

These findings were made by a multi-institutional research collaboration, which included Associate Professor INUI Hideyuki (Kobe University Biosignal Research Center), Lead Researcher MATSUMURA Chisato (Hyogo Prefectural Institute of Environmental Sciences), Professor YAMAMOTO Keiko and Professor ITOH Toshimasa (Showa Pharmaceutical University), Associate Professor MORI Tadashi (Osaka University Graduate School of Engineering), and Visiting Professor NAKANO Takeshi (Osaka University Research Center for Environmental Preservation).

These research results were published online in the international academic journals Environmental Science & Technology on July 8, and Chemosphere on September 6, 2022.

Main points

  • In the past, PCBs were utilized in a vast range of industrial and commercial products. These highly carcinogenic chemical compounds remain in our environment and accumulate inside organisms.
  • PCBs have a dioxin-like toxicity and research into PCB metabolism is advancing.
  • However, research had yet to uncover how chiral PCBs’ mirror-image isomers are metabolized.
  • The researchers split the two atropisomers (mirror-image isomers) found in each type of chiral PCB and used them as substrates for CYP enzymes (*4).
  • Even though a pair of atropisomers are physically and chemically identical, there was a big difference in the extent to which they were metabolized.
  • Differences in CYP’s amino acids’ binding inhibition of each atropisomer cause the atropisomers to be metabolized differently.
  • These findings will be useful for measuring the atropisomers of chiral PCBs, which accumulate easily inside animals’ bodies.

Research Background

Even though the manufacture and use of PCBs was banned around 50 years ago, they still remain in the environment. It has been discovered that PCBs accumulate inside the bodies of humans and other animals through food consumption. In particular, PCBs with many chlorine bonds are water resistant and do not break down easily. This enables high concentrations of these PCBs to accumulate inside animals’ bodies, which adversely affects their health. PCBs’ toxicity is induced by the aryl hydrocarbon receptor (AhR) (*5), causing similar adverse effects to dioxin (*6) poisoning such as cancer, teratogenesis and immune system damage. Research is being conducted on the particular types of PCB widely known to cause these effects, which are dioxin-like PCBs with one ortho chlorine substitution in the biphenyl ring of their chemical structure, or PCBs with no substitutions. However, if a PCB has more than 3 chlorine substitutions at the ortho position of the biphenyl ring, it becomes a mirror-image isomer called chiral PCB. These chiral PCBs do not demonstrate dioxin-like toxicity but are far more dangerous, binding with the ryanodine receptors (RyR) in organisms to become neurotoxic. The two mirror-image isomers (called atropisomers) in chiral PCB have identical physical and chemical properties and exist at a 1:1 ratio in commercial chiral PCB. However, biased ratios are often observed in the environment and in animals such as earthworms and whales, as well as humans. It is believed that this unbalanced ratio is mainly caused by metabolism and that one of chiral PCB’s atropisomers is more effected by the metabolic reaction thus reducing its concentration.

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