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.

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).

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

Endometriosis

The Endocrine Society's first Scientific Statement in 2009 provided a wake-up call to the scientific community about how environmental endocrine-disrupting chemicals (EDCs) affect health and disease. Five years later, a substantially larger body of literature has solidified our understanding of plausible mechanisms underlying EDC actions and how exposures in animals and humans-especially during development-may lay the foundations for disease later in life. At this point in history, we have much stronger knowledge about how EDCs alter gene-environment interactions via physiological, cellular, molecular, and epigenetic changes, thereby producing effects in exposed individuals as well as their descendants. Causal links between exposure and manifestation of disease are substantiated by experimental animal models and are consistent with correlative epidemiological data in humans. There are several caveats because differences in how experimental animal work is conducted can lead to difficulties in drawing broad conclusions, and we must continue to be cautious about inferring causality in humans. In this second Scientific Statement, we reviewed the literature on a subset of topics for which the translational evidence is strongest: 1) obesity and diabetes; 2) female reproduction; 3) male reproduction; 4) hormone-sensitive cancers in females; 5) prostate; 6) thyroid; and 7) neurodevelopment and neuroendocrine systems. Our inclusion criteria for studies were those conducted predominantly in the past 5 years deemed to be of high quality based on appropriate negative and positive control groups or populations, adequate sample size and experimental design, and mammalian animal studies with exposure levels in a range that was relevant to humans. We also focused on studies using the developmental origins of health and disease model. No report was excluded based on a positive or negative effect of the EDC exposure. The bulk of the results across the board strengthen the evidence for endocrine health-related actions of EDCs. Based on this much more complete understanding of the endocrine principles by which EDCs act, including nonmonotonic dose-responses, low-dose effects, and developmental vulnerability, these findings can be much better translated to human health. Armed with this information, researchers, physicians, and other healthcare providers can guide regulators and policymakers as they make responsible decisions.

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EDC-2: The Endocrine Society's Second Scientific Statement on Endocrine-Disrupting Chemicals

https://apps.who.int/iris/bitstream/10665/78102/1/WHO_HSE_PHE_IHE_2013.1_eng.pdf

State of the Science of Endocrine Disrupting Chemicals - 2012

Chlorodibenzo-p-dioxins and chlorodibenzofurans are trace components of fly ash and flue gas of some municipal incinerators in The Netherlands

Polychlorinated dibenzo-p-dioxins and polychlorinated dibenzofurans are toxic compounds formed during natural processes and human activities. The basic questions about PCDD/F formation such as (1) what is the influence of process parameters on the formation process, (2) what reaction mechanisms are involved in formation, and (3) what kinetics describes PCDD/F formation are discussed, and recommendations are given.

/pdf/mechanisms-of-formation-and-destruction-of-polychlorinated-2xrxak2528.pdf

Mechanisms of Formation and Destruction of Polychlorinated Dibenzo=p=dioxins and Dibenzofurans in Heterogeneous Systems

Chlorinated dibenzo-p-dioxins and related compounds in incinerator effluents: A review of measurements and mechanisms of formation

~~~ Combustion experiments of an activated carbon (Norit RX Extra), catalyzed by CuC12, were conducted in triplicate in a flow of moist air containing 5 vol % HC1 at 300 "C to reveal the mechanism of formation of polychlorinated dibenzo-p-dioxins (PCDDs) and polychlorinated dibenzofurans (PCDFs). The catalyst concentration was varied from 0, 0.1,0.5,1.0, to 5.0 wt %. After partial combustion (1 h), the samples were analyzed on the presence of PCDDs and PCDFs. The total yield of these compounds amounted to 19 (0.1 wt % CuC12) and 2 (5.0 wt % CuClz) pg/g of carbon. The PCDD/PCDF ratio showed a decrease from 33 to 0.2. At low copper concentrations, predominantly PCDDs are formed with an isomer pattern that can be explained completely as a product of chlorophenol condensation reactions. At high copper concentrations, the PCDD/PCDF isomer distribution pattern shifts toward a characteristic waste incineration fly ash pattern. A proposal for the mechanism of formation of PCDDs and PCDFs in the catalyzed combustion of carbon will be presented. Condensation reactions of 2,4,6-trichlorophenol on carbon (Owt 9% CuC12) resulted in the formation of predominantly PCDDs with an identical isomer distribution pattern as observed in the catalyzed combustion of carbon. Active carbon was shown to catalyze the condensation reaction of 2,4,6trichlorophenol into PCDDs.

/pdf/mechanism-of-formation-of-polychlorinated-dibenzo-p-dioxins-3f0mrf2807.pdf

Kees Olie

Papers

Chlorodibenzo-p-dioxins and chlorodibenzofurans are trace components of fly ash and flue gas of some municipal incinerators in The Netherlands

Mechanisms of Formation and Destruction of Polychlorinated Dibenzo=p=dioxins and Dibenzofurans in Heterogeneous Systems

Chlorinated dibenzo-p-dioxins and related compounds in incinerator effluents: A review of measurements and mechanisms of formation

Mechanism of formation of polychlorinated dibenzo-p-dioxins and dibenzofurans in the catalyzed combustion of carbon.

Chlorinated dibenzo-p-dioxins and related compounds in incinerator effluents