Toxicology, structure-function relationship, and human and environmental health impacts of polychlorinated biphenyls: progress and problems.

Abstract

Polychlorinated biphenyls (PCBs) are industrial compounds that have been detected as contaminants in almost every component ofthe global ecosystem including the air, water, sediments, riu, and wildlife and human adipose tissue, milk, and serum. PCBs in commercial products and environmental extracts are complex mixtures of isomers and congeners that can now be analyzed on a congener-specific basis using high-resolution gas chromatographic analysis. PCBs are metabolized prarily via mixed-function adxdaes intoa broadspectrum of m-tIbolites. The resuts indicate that metabolk activation is not required for PCB toxicity, and the parent hydrocarbons are responsible for most of the biochemical and toxic responses elicited by these compounds. Some of these responses include developmental and reproductive toxicity, dermal toxicity, endocrine effects, hepatotoxicity, carcinogenesis, and the induction of diverse phase I and phase I drugmetabolizing enzymes. Many of the effects observed for the commercial PCBs are similar to those reported for 2,3,7,-tetrachlorodibenzo-p-dioxin (TCDD) and related compounds. Strctur-function relaionships for PCB congeners have identified two major stnctural classes ofPCBs that elicit "TCDD-lik"' responses, namely, the coplanar PCBs (e.g., 3,3',4A,'-tetraCB, 3,3' 4,4 ,5-pentaCB and 3,3',4,4,,5'-hexaCB) and their mono-ortho coplanar derivatives. These compounds competitively bind to the TCDD or aryl hydrocarbon (Ah) receptor and exhibit Ah receptor agonist activity. In addition, other structural dasses of PCBs elicit biochemical and toxic responses that are not mediated through the Ah receptor. The shor-term effects of PCBs on occupationally exposed humans appear to be reversible, and no consistent changes in overall mortality and cancer mortality have been reported. Recent studies have demonstrated that some developmental deficits in infants and children correlated with in utero exposure to PCBs; however, the etiologic agent(s) or structural clas of PCBs responsible for these effects have not been dlinated. In contrast, based on a toxic equivalency factor approach, the reproductive and developmental problems in certain wildlife populations appear to be related to the TCDD-like PCB congeners.

A comprehensive model for chemical bioavailability and toxicity of organic chemicals based on first principles

“…3 ,4, has an energy gap of 4.87 eV, which is proposed as a threshold energy gap for toxic potency of dioxin-like PCBs (see Figure 1). The results of these predictions are consistent with those of other studies showing that coplanar PCBs are more toxic through AhRmediated mechanisms than are the di-ortho-substituted PCBs (Safe, 1993;Van den Berg et al, 2006). There was a relatively narrow distribution of HOMO-LUMO gaps among coplanar PCBs, with a range of 0.35 eV for all coplanar and only 0.09 eV for dioxin-like congeners.…”

“…Most research into the toxicity of AhR-agonists and other chemicals has focused on assays with actual biomaterial, which can be time-consuming and require use of live animals. Alternatively, modern molecular techniques and in silico studies of quantitative structure-activity relationship (QSAR) methods are being used more and more to predict biological activities of organic molecules (Safe, 1993;Yang et al, 2009Yang et al, , 2010. Such approaches are, however, limited in their ability to explain the inherent nature of bioactivity (viz., potential toxicity) of chemicals because of their case-or compound-specific masking effects (Safe, 1993;Chana et al, 2002).…”

Railway Tracks - Habitat Conditions, Contamination, Floristic Settlement - A Review

“…PCBs became widely used as lubricants, fire-resistant dielectric fluids in transformers and capacitors and heat-transfer fluids up to the mid of 1970s. Due to their persistence and lipophilic properties, which lead to their bioaccumulation in living organisms, they became a serious threat to natural environments (Bracewell et al, 1993;Safe, 1984Safe, , 1989aSafe, , 1989b.…”

Polychlorinated biphenyls and polybrominated biphenyls

“…There is evidence that most known PCBs are subject to biotransformation (metabolism) in humans and other animals through enzymatic processes (Safe, 1993). Biotransformation is important for the eventual elimination of PCBs from the body, as most (but not all) of the metabolites are more water-soluble than the parent compound.…”

“…For example, many congeners with no or one ortho chlorine are metabolized by CYP1A1 or CYP1A2 (Curran et al, 2011), and these congeners, like dioxin, polycyclic aromatic hydrocarbons and some components of tobacco smoke, induce CYP1A1 and CYP1A2 by binding to and activating AhR Safe, 1993). CYP1B1 is also induced by compounds that bind and activate AhR (Murray et al, 2001).…”