Metabolism and biochemical toxicity of PCBs and PBBs

Matthews, H. B.; Fries, George F.; Gardner, Albert M; Garthoff, Larry H.; Goldstein, Joyce A.; Ku, Yang Gyu; Moore, J. A.

doi:10.1289/ehp.7824147

Cited by 57 publications

(10 citation statements)

References 84 publications

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“…Translocation of the inducer-receptor complex to the nuclear Ah locus is thought to initiate the synthesis of AHH, EROD, and related enzymes that may be involved in either biotransformation, conjugation and removal, or the bioactivation of certain planar lipophilic foreign compounds to toxic intermediates (46,47,49). The most toxicologically active PCB congeners are those having chlorine substitution at the para (4 and 4') and at least two meta (3,35, and 5') positions on the biphenyl nucleus, but no ortho (2,2,6, and 6') substitutions (Fig. la,b) (24).…”

Section: Molecular Structure and Pcb Congener Lbxicitymentioning

confidence: 99%

“…In addition, the data regarding the toxicity of individual PCB congeners to aquatic biota are scant and often contradictory. However, the evidence for PCB congener-specific toxicity to higher vertebrates is much better developed, and it is now known that a large group of halogenated hydrocarbons that are approximately isosteric (including certain of the PCBs) elicit similar biochemical and toxic effects and appear to act by the same or similar mechanisms (45)(46)(47)(48)(49)(50). It is beyond the scope of this report to review the large body of literature reporting research in mammalian and avian toxicology of halogenated aromatic compounds, including the PCBs [for a comprehensive review, see Kimbrough (51)].…”

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confidence: 99%

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Environmental occurrence, abundance, and potential toxicity of polychlorinated biphenyl congeners: considerations for a congener-specific analysis.

McFarland

Clarke

1989

Environ Health Perspect

621

279

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Polychlorinated biphenyls (PCBs) as environmental contaminants often cannot be adequately described by reference to Aroclors or to total PCBs. Although there are 209 possible PCB configurations (congeners), perhaps half that number account for nearly all of the environmental contamination attributable to PCBs. Still fewer congeners are both prevalent and either demonstrably or potentially toxic. If potential toxicity, environmental prevalence, and relative abundance in animal tissues are used as criteria, the number of environmentally threatening PCB congeners reduces to about thirty-six. Twenty-five of these account for 50 to 75% of total PCBs in tissue samples of fish, invertebrates, birds, and mammals.A few PCB congeners that are sterically similar to 2,3,7,3,7, are directly toxic. Other PCB congeners, as well as those that are directly toxic, may also be involved in toxicity indirectly by stimulating the production of (inducing) bioactivating enzyme systems. The most consequential of these have the ability to induce aryl hydrocarbon metabolizing mixed-function oxidases (MFOs). A result can be an increased capacity for bioactivation of otherwise nontoxic foreign compounds such as certain polynuclear aromatic hydrocarbons (PAH) to cytotoxic or genotoxic metabolites. The effectiveness of specific PCB congeners as inducers of different types of cytochrome P-450-dependent MFO systems is determined by their stereochemistry. Although MFO induction is not a proximate cause, it is a strong correlate of certain kinds of toxicities. Structural patterns can thus be used to discriminate among PCB congeners on the basis of toxic potential, if not entirely on toxicity per se. Congeners that demonstrate 3-methylcholanthrene-type (3-MCtype) and mixed-type MFO induction have the greatest toxic potential. These congeners most closely resemble 2,3,7,8-TCDD in their structures and in their toxic effects. The larger group of phenobarbital-type (PBtype) inducers have considerably less potential for contributing to toxic effects. Weak inducers and noninducing congeners have the least potential for toxicity.Using the rationale described in this paper, we assigned the most environmentally threatening PCB congeners to four groups. Congeners assigned to Group 1 are considered most likely to contribute to adverse biological effects attributable to PCBs in an environmental sample. Group 1A contains the three most potent (pure 3-MC-type inducer) congeners, IUPAC numbers 77, 126, and 169. Six congeners, numbers 105, 118, 128, 138, 156, and 170, are assigned to Group 1B. These congeners are mixed-type inducers that have been reported frequently in environmental samples. Group 2 congeners are PB-type inducers that are also prevalent in the environment; these include numbers 87, 99, 101, 153, 180, 183, and 194. Group 3 congeners, numbers 18,44,49,52,70,74, 151, 177, 187, and 201, are weak or noninducers, but they occur frequently in the environment or in high concentrations in animal tissues relative to other PCB congeners, and so may be of ...

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Section: Molecular Structure and Pcb Congener Lbxicitymentioning

confidence: 99%

mentioning

confidence: 99%

Environmental occurrence, abundance, and potential toxicity of polychlorinated biphenyl congeners: considerations for a congener-specific analysis.

McFarland

Clarke

1989

Environ Health Perspect

621

279

View full text Add to dashboard Cite

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“…The effects which were more pronounced with Firemaster BP-6 were an enlarged liver, an increase in liver cholesterol and plasma cholesterol and a decrease in liver RNA synthesis. Firemaster BP-6 was also found to be about three times more potent than Aroclor 1254 in inducing microsomal enzyme activities (86).…”

Section: General Toxicity Of Pbbsmentioning

confidence: 94%

Toxicity of polybrominated biphenyls (PBBs) in Domestic and laboratory animals.

Damstra¹,

Jurgelski²,

Posner³

et al. 1982

Environ Health Perspect

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The composition, environmental fate, and effects of the polybrominated biphenyls (Firemaster BP-6 or FF-1) involved in the accidental contamination of cattle feed in Michigan in 1973 are reviewed. Toxic effects referred to in this report are limited to those occurring in domestic and laboratory animals and include general toxicity, neurobehavioral toxicity, immunotoxicity, reproductive toxicity, mutagenicity and carcinogenicity. The absorption, distribution, biotransformation and elimination of these polybrominated biphenyls are discussed along with the interactions with other chemicals and drugs.

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“…In rats exposed to PBBs, the ability to mount an antibody response to an Much less research has been conducted on PBBs than on PCBs. Commercial PBB mixtures are associated with equivalent or greater toxicity than their chlorinated analogues (Matthews et al, 1978;Andres et al, 1983). It is likely that the congeneric PBBs exhibit their toxicity and disease potential via many of the same pathways as their chlorinated counterparts.…”

Section: Organ Toxicitymentioning

confidence: 99%

Polychlorinated Biphenyls and Polybrominated Biphenyls

Agudo

Aronson²,

Bonefeld-Jörgensen³

et al. 2008

Organic Pollutants

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initiated a programme on the evaluation of the carcinogenic risk of chemicals to humans involving the production of critically evaluated monographs on individual chemicals. The programme was subsequently expanded to include evaluations of carcinogenic risks associated with exposures to complex mixtures, lifestyle factors and biological and physical agents, as well as those in specific occupations. The objective of the programme is to elaborate and publish in the form of monographs critical reviews of data on carcinogenicity for agents to which humans are known to be exposed and on specific exposure situations; to evaluate these data in terms of human risk with the help of international working groups of experts in carcinogenesis and related fields; and to indicate where additional research efforts are needed. The lists of IARC evaluations are regularly updated and are available on the Internet at http:// monographs.iarc.fr/.This programme has been supported since 1982 by Cooperative Agreement U01 CA33193 with the United States National Cancer Institute, Department of Health and Human Services. Additional support has been provided since 1986 by the European Commission Directorate-General for Employment, Social Affairs, and Inclusion, initially by the Unit of Health, Safety and Hygiene at Work, and since 2014 by the European Union Programme for Employment and Social Innovation "EaSI" (2014-2020) The International Agency for Research on Cancer welcomes requests for permission to reproduce or translate its publications, in part or in full. Requests for permission to reproduce or translate IARC publications -whether for sale or for non-commercial distribution -should be addressed to the IARC Communications Group at: publications@iarc.fr.The designations employed and the presentation of the material in this publication do not imply the expression of any opinion whatsoever on the part of the Secretariat of the World Health Organization concerning the legal status of any country, territory, city, or area or of its authorities, or concerning the delimitation of its frontiers or boundaries.The mention of specific companies or of certain manufacturers' products does not imply that they are endorsed or recommended by the World Health Organization in preference to others of a similar nature that are not mentioned. Errors and omissions excepted, the names of proprietary products are distinguished by initial capital letters.The IARC Monographs Working Group alone is responsible for the views expressed in this publication. IARC Library Cataloguing in Publication Data NOTE TO THE READERThe term 'carcinogenic risk' in the IARC Monographs series is taken to mean that an agent is capable of causing cancer. The Monographs evaluate cancer hazards, despite the historical presence of the word 'risks' in the title.Inclusion of an agent in the Monographs does not imply that it is a carcinogen, only that the published data have been examined. Equally, the fact that an agent has not yet been evaluated in a Monograph does not mean that...

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Metabolism and biochemical toxicity of PCBs and PBBs

Cited by 57 publications

References 84 publications

Environmental occurrence, abundance, and potential toxicity of polychlorinated biphenyl congeners: considerations for a congener-specific analysis.

Environmental occurrence, abundance, and potential toxicity of polychlorinated biphenyl congeners: considerations for a congener-specific analysis.

Toxicity of polybrominated biphenyls (PBBs) in Domestic and laboratory animals.

Polychlorinated Biphenyls and Polybrominated Biphenyls

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