Polychlorinated dibenzofuran congeners

Structure can be observed by the loss of dioxin-like activities of PCBs with ring substitution(s) at one or more of the ortho (2,2 6,6 -) position(s) which can lead to distortion from planar structure. Subsequent AhR binding data indicated that polychlorinated dibenzofuran congeners have binding activity similar to that of their dibenzo-p-dioxin counterparts (Woo and Lai 2003). 

Fraser CA, Gardner GJ, Maxwell PS, Kubwabo C, Guevremont R, Siu KWM, and Berman SS (1995) Preparation and certification of a biological reference material (CARP-i) for polychlorinated dibenzo-p-dioxin and dibenzofuran congeners. Fresenius J Anal Chem 352 143-147. Gahr A, Huber N, and Niessner R (1998) Fluorimetric determination of bromate by ion-exchange separation and post-column derivatization. Mikrochrm Acta 129 281-290. 

There are 75 possible isomers of polychlorinated-p-dibenzodioxin (PCDD) and 135 such isomers of polychlorinated dibenzofuran (PCDF). These related compounds are known as congeners. In addition, PCBs form a similar group of 209 related congeners that differ only in the number and pattern of chlorine atoms attached to the parent biphenyl molecule. 

Knutzen, J., Bjerkeng, B., Naes, K., Schlabach, M., 2003. Polychlorinated dibenzofurans/ dibenzo-p-dioxins (PCDF/PCDDs) and other dioxin-like substances in marine organisms from the Greenland fjords, S. Norway, 1975-2001 Present contamination levels, trends and species specific accumulation of PCDF/PCDD congeners. Chemosphere 52, 745-760. 

Holcomb M, Yao C, Safe S. 1988. Biologic and toxic effects of polychlorinated dibenzo-p-dioxin and dibenzofuran congeners in the guinea pig Quantitative structure-activity relationships. Biochem Pharmacol 37 1535-1539. 

Zacharewski T, Safe L, Safe S, et al. 1989. Comparative analysis of polychlorinated dibenzo-p-dioxin and dibenzofuran congeners in Great Lakes fish extracts by gas chromatography and in vitro enzyme induction activities. Environ Sci Technol 23 730-735. 

Dioxin A family of chemicals with related properties and toxicity. There are 75 different dioxins, or polychlorinated dibenzodioxins (PCDDs) 135 different furans, or polychlorinated dibenzofurans (PCDFs) and 209 different polychlorinated biphenyls (PCBs). Each different form is called a congener, a member of a family of compounds known chemically as dibenzo-p-dioxins. Concern about them arises from their potential toxicity as contaminants in commercial products. Tests on laboratory animals indicate that it is one of the more toxic anthropogenic (man-made) compounds a term used interchangeably with 2,3,7,8-tetrachlorodibenzo-p-dioxin or TCDD Disease prevention Measures used to prevent a disease or reduce its severity Dispersoids The particles of a dispersion... 

Polychlorinated dibenzofurans (PCDFs) are formed as inadvertent by-products in the production and use of polychlorinated biphenyls (PCBs), formerly used as an insulator in electrical transformers and, in combination with polychlorinated dibenzo-p-dioxins (PCDDs), in the production of chlorophenols and have been detected as contaminants in these products. PCDFs and PCDDs also may be produced in thermal processes such as incineration and metal processing and in the bleaching of paper pulp with free chlorine. PCDFs are also found in residual waste from the production of vinyl chloride and the chlor-alkali process for chlorine production. The relative amounts of PCDF and PCDD congeners produced... 

These SAR considerations have been captured in EPA s OncoLogic Cancer Expert System for predicting carcinogenic potential of chemicals completed in 1999-2000 (Woo and Lai 2005 Woo et al. 1995). In 2006, the NTP completed the cancer bioassay of a number of new congeners of polychlorinated dibenzofurans and PCBs. The results of these studies are summarized in the table below and compared to the OncoLogic predictions. As can be seen from the table, the mechanism-based SAR approach of the OncoLogic system allowed the system to accurately predict the carcinogenic activities. 

CK on the fecal excretion of polychlorinated dibenzo-/ -dioxin (PCDD) congeners and polychlorinated dibenzofuran (PCDF) congeners in rats administered the dioxin mixture [3]. 

Figure 1 Effects of Chlorella diet on fecal excretion amounts of polychlorinated dibenzo-p-dioxin (PCDD) and polychlorinated dibenzofuran (PCDF) congeners in contaminated rice oil-fed rats. Values are means SD, n=4. Vhlues of acceleration index of fecal excretion amounts of PCDD and PCDF congeners due to Chlorella diet were calculated using the following equation Acceleration index of fecal excretion amounts of PCDD...

Nordgren, andU. G. Ahlborg. 1991. Relative liver tumour promoting activity and toxicity of some polychlorinated dibenzo-p-dioxin- and dibenzofuran—congeners in female Sprague-Dawley rats. Pharmacol. Toxicol. 69(6) 450—58. 

Polychlorinated dibenzodioxins (PCDDs), polychlorinated dibenzofurans (PCDFs), and polychlorinated biphenyls (PCBs) are chemically classified as halogenated aromatic hydrocarbons. The chlorinated and brominated dibenzodioxins and dibenzofurans are tricyclic aromatic compounds with similar physical and chemical properties, and both classes are similar structurally. Certain of the PCBs (the so-called coplanar or mono-ortho coplanar congeners) are also structurally and conformationally similar. The most widely studied of these compounds is 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD). This compound, often called simply dioxin, represents the reference compound for this class of compounds. The structure of TCDD and several related compounds is shown in Figure 4.1. 

Individual PCB congeners differ by their biological effects. Toxicological studies have shown that some congeners act by the same mechanisms as polychlorinated dibenzo-p-dioxins (PCDD) and polychlorinated dibenzofurans (PCDF), whose toxicity is mediated by interaction with a protein receptor. Other PCBs act by totally different mechanisms. 

Walker, M.K. and R.E. Peterson. 1991. Potencies of polychlorinated dibenzo-p-dioxin, dibenzofuran, and biphenyl congeners, relative to 2,3,7,8-tetrachlorodibenzo-p-dioxin, for producing early life stage mortality in rainbow trout (Oncorhynchus mykiss). Aquat. Toxicol. 21 219-238. 

Polychlorinated hydrocarbons, such as polychlorinated dibenzodioxins, dibenzofurans, and biphenyls exist as a number of different congeners. Some of these are geometric isomers. Many cause a range of toxic effects that are believed to be mediated by interaction with the aryl hydrocarbon receptor (AhR) (they are known as pleiotropic effects). However, not all the isomers cause these effects because they do not all interact with the AhR receptor. To interact with this receptor, the molecule needs to be flat (planar). It can be seen in the diagram (Fig. 5.2)... 

---