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Journal ArticleDOI

Polychlorinated biphenyls (PCBs), dibenzo-p-dioxins (PCDDs), dibenzofurans (PCDFs), and related compounds: environmental and mechanistic considerations which support the development of toxic equivalency factors (TEFs).

Stephen Safe
- 01 Jan 1990 - 
- Vol. 21, Iss: 1, pp 51-88
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TLDR
The most toxic halogenated aromatic is 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) and based on in vivo and in vitro studies the relative toxicities have been determined relative to TCDD (i.e., toxic equivalents).
Abstract
Halogenated aromatic compounds, typified by the polychlorinated dibenzo-p-dioxins (PCDDs), dibenzofurans (PCDFs), biphenyls (PCBs), and diphenylethers (PCDEs), are industrial compounds or byproducts which have been widely identified in the environment and in chemical-waste dumpsites. Halogenated aromatics are invariably present in diverse analytes as highly complex mixtures of isomers and congeners and this complicates the hazard and risk assessment of these compounds. Several studies have confirmed the common receptor-mediated mechanism of action of toxic halogenated aromatics and this has resulted in the development of structure-activity relationships for this class of chemicals. The most toxic halogenated aromatic is 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) and based on in vivo and in vitro studies the relative toxicities of individual halogenated aromatics have been determined relative to TCDD (i.e., toxic equivalents). The derived toxic equivalents can be used for hazard and risk assessment of halogenated aromatic mixtures; moreover, for more complex mixtures containing congeners for which no standards are available (e.g., bromo/chloro mixtures), several in vitro or in vivo assays can be utilized for hazard or risk assessment.

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Journal ArticleDOI

Polychlorinated Biphenyls (PCBs): Environmental Impact, Biochemical and Toxic Responses, and Implications for Risk Assessment

TL;DR: Analysis of the results of laboratory animal and wildlife studies suggests that the predictive value of TEQs for PCBs may be both species- and response-dependent because both additive and nonadditive (antagonistic) interactions have been observed with PCB mixtures.
Journal ArticleDOI

Activation of the aryl hydrocarbon receptor by structurally diverse exogenous and endogenous chemicals.

TL;DR: Evidence for the structural promiscuity of AhR ligand binding is described and the current state of knowledge with regards to the activation of the AhR signaling pathway by naturally occurring exogenous and endogenous ligands is discussed.
Journal ArticleDOI

Male reproductive health and environmental xenoestrogens

TL;DR: The growing number of reports demonstrating that common environmental contaminants and natural factors possess estrogenic activity presents the working hypothesis that the adverse trends in male reproductive health may be, at least in part, associated with exposure to estrogenic or other hormonally active environmental chemicals during fetal and childhood development.
Journal ArticleDOI

Polybrominated diphenyl ethers: occurrence, dietary exposure, and toxicology.

TL;DR: Based on the scientific knowledge of today and based on Nordic intake data, the possible consumer health risk from PBDEs appears limited, as a factor of over 10 separates the estimated present mean dietary intake from the suggested LOAEL value.
References
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Journal ArticleDOI

2,3,7,8-Tetrachlorodibenzo-p-Dioxin and Related Halogenated Aromatic Hydrocarbons: Examination of the Mechanism of Toxicity

TL;DR: The toxicity of halogenated aromatic hydrocarbons appears to be due to the sustained expression of a normal cellular regulatory system, of which the author was previously unaware.
Journal ArticleDOI

Stereospecific, high affinity binding of 2,3,7,8-tetrachlorodibenzo-p-dioxin by hepatic cytosol. Evidence that the binding species is receptor for induction of aryl hydrocarbon hydroxylase.

TL;DR: The data suggest that the hepatic cytosol species which binds TCDD is the receptor for the induction of hepatic aryl hydrocarbon hydroxylase activity, and that the mutation in nonresponsive mice results in an altered receptor with a diminished affinity for inducing compounds.
Journal ArticleDOI

Results of a two-year chronic toxicity and oncogenicity study of 2,3,7,8-tetrachlorodibenzo-p-dioxin in rats

TL;DR: It is indicated that continuous doses of TCDD sufficient to induce severe toxicity increased the incidence of some types of tumors, while reducing other types, and no increase in tumors occurred in those rats receiving sufficient TCDDs to induce slight or no manifestations of toxicity.
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