POLYCHLORINATED BIPHENYLS (PCB) TOXICOLOGY

Polychlorinated Biphenyls (PCB) Toxicology

Abstract

Polychlorinated biphenyls (PCBs) are a group of 209 persistent environmental contaminants that are slightly different but structurally related. PCBs are known to induce a variety of health effects and often have been toxicologically tested as complex commercial mixtures (Aroclors) but environmental exposure occurs separately to a small number of specific congeners. Recently, the Third National Report on Human Exposures to Environmental Chemicals, an assessment of exposure data of the National Health and Nutrition Examination Survey (NHANES), identified 35 individual PCB congeners in the U.S. population. These types of findings necessitate the toxicity evaluation of individual congeners but adequate toxicity data for most individual PCB congeners are not available. Due to this, a quantitative structure-activity relationship (QSAR) approach was used to assess the potential mutagenesis and carcinogenesis of individual congeners and their possible metabolites. The predictions were analyzed to define the underlying generalizations between the parent PCBs, their metabolites, and some important toxicological endpoints. This analysis reveals that (1) mono and di-chlorinated PCBs and their metabolites can be potential mutagens; (2) PCB benzoquinone metabolites could be carcinogenic but the weight of evidence is poor. These results support the hypothesis that environmental exposure to some PCBs and/or their metabolites could produce mutagenicity and/or carcinogenicity. Hence, these data should be considered as priority toxicological testing data needs. As with all computational toxicology analytical findings, these conclusions must yield to empirical data as they become available.

Table of Contents

Introduction4

Methods6

Models protocol7

Ames mutagenicity model7

NTP Rodent Carcinogenicity models8

Results8

Discussion14

Conclusions16

References18

Polychlorinated Biphenyls (PCB) Toxicology

Introduction

Polychlorinated biphenyls (PCBs) are worldwide environmental pollutants that constitute a group of 209 different congeners and their mixtures, possessing a wide spectrum of toxic effects. Their potency and nature of toxicity is dependent on the number and sites of chlorine substitution. PCBs were extensively used in the electrical utility industry in capacitors, transformers, hydraulic fluids, paints, plasticizers, and a variety of other commercial products. They are ubiquitous contaminants andbecause of their persistent characteristics and the production of these chemicals has been banned for three decades but a significant amount of PCBs purchased by industry are still in use. However, they are still found in rivers, lakes, soil, atmosphere, fish wildlife, animals and humans (Anderson, 1991, 455).

Humans are exposed to PCBs through air, water, soil, and food. Exposure to background levels of PCBs occurs mainly via the food chain. Occupational exposure to high levels of individual congeners can occur at the sites of manufacture, through accidental contamination, and from technical use in buildings. In such scenarios direct exposures to complex mixtures may also occur as their available commercial mixtures. Exposure through ingestion occurs from contaminated food, especially from fish and mother's milk. Apart from direct exposures, actual exposures to PCBs are very complex and hard to quantify. PCBs have been found in human tissues including milk, blood and adipose tissue. Also, the recent third national report on human exposures to environmental chemicals based on the National Health and Nutrition Examination Survey (NHANES) identified 35 individual PCB congeners in blood samples of ...