2,3,7,8-Tetrachloro-dibenzo-p-dioxin

Ah-receptor-mediated toxicity is particularly associated with the highly toxic compound 2,3,7,8-tetrachloro-dibenzo-p-dioxin (TCDD), commonly referred to as dioxin. TCDD, and the concept of toxicity equivalency factors (TEFs) based on TCDDs, will be dealt with in Chapter 7. The main point to make at this juncture is that the toxicity of each individual coplanar congener in a mixture can be expressed in terms of a toxic equivalent calculated relative to the toxicity of dioxin. Summation of the toxic equivalents of the individual coplanar PCBs gives a measure of the toxicity of the whole mixture, as expressed through the Ah receptor mechanism. 

Decomposition products were captured in two traps immersed in dry ice followed by a third trap containing 5 ml of benzene. After 1 hour, the boat, tube, and traps were rinsed with benzene. The benzene solution was analyzed by gas chromatography using an electron capture detector to determine the concentration of unreacted 2,3,7,8-tetrachloro-dibenzo-p-dioxin. 

The initial concern for the possible hazard to humans exposed to 2,4,5-T was precipitated by teratologic studies conducted by Bionetics Research Institute under contract from The National Cancer Institute (2). In these studies, large doses of 2,4,5-T were administered to pregnant rats and mice for nine of the 21 days of pregnancy. The incidence of fetal abnormalities was slightly higher in the treated animals than in control animals. Later tests indicated that these abnormalities (cleft palate) may have been caused by 27 8 ppm of 2,3,7,8-tetrachloro-dibenzo-p-dioxin present as a contaminant in the 2,4,5-T sample used in the Bionetic study (3). After the results of the study were made known, the Panel on Herbicides of the President s Science Advisory Committee studied the total 2,4,5-T situation. The report of this committee was published in March, 1971 (4). 

The bleaching process, in contrast, poses major difficulties. Traditional paper bleaching uses chlorine gas, which is reduced to chloride anions, cr, as it oxidizes the colored pigments in wood pulp. The chloride anion is not a pollutant, as it is a major species in the oceans. Unfortunately, chlorine processing also generates small quantities of chlorine-containing dioxins such as 2,3,7,8-tetrachloro-dibenzo-p-dioxin, whose stmcture (below) appears less formidable than its name ... 

Neubert, R., G. Golor, R. Stahlmann, H. Helge, and D. Neubert. 1992. Polyhalogenated dibenzo-p-dioxins and dibenzofurans and the immune system. 4. Effects of multiple-dose treatment with 2,3,7,8-tetrachloro-dibenzo-p-dioxin (TCDD) on peripheral lymphocyte subpopulations of a non-human primate (Callithrix jacchus). Arch. Toxicol. 66 250-259. 

Vorderstrasse, B., Dearstyne, E. A., and Kerkvliet, N. I., Influence of 2,3,7,8-tetrachloro-dibenzo-p-dioxin on the antigen-presenting activity of dendritic cells, Toxicol. Sci., 72, 103, 2003. 

House, R., Lauer, L., and Murray, M., Examination of immune parameters and host resistance mechanisms in B6C3F1 mice following adult exposure to 2,3,7,8-tetrachloro-dibenzo-p-dioxin, J. Toxicol. Environ. Health, 31, 203, 1990. 

Chatteijee, A., Onodera, Y., Ebina, T., and Mizukami, F. 2003. 2,3,7,8-tetrachloro dibenzo-p-dioxin can be successfully decomposed over 2 1 dioctahedral smectite—a reactivity index study. J. Mol. Graphics Model. 22 93-104. 

Polychlorinated Dibenzo-(p)-Dioxins and Dibenzo-Furans. Another group of compounds that we need to specifically address are the polychlorinated dibenzo-p-dioxins (PCDDs) and dibenzo-furans (PCDFs) (Fig. 2.15). The PCDDs and PCDFs are not intentionally produced but are released into the environment from various combustion processes and as a result of their occurrence as unwanted byproducts in various chlorinated chemical formulations (e.g., chlorinated phenols, chlorinated phenoxy herbicides see Alcock and Jones, 1996). Because some of the PCDD and PCDF congeners are very toxic (e.g., 2,3,7,8-tetrachloro dibenzo-p-dioxin, see margin), there have been and still are considerable efforts to assess their sources, distribution, and fate in the environment. Similarly to the PCBs or DDT (see above), the PCDDs and PCDFs are highly hydrophobic and very persistent in the environment. It is therefore not surprising that they have also been detected everywhere on earth (Brzuzy and Hites, 1996 Lohmann and Jones, 1998 Vallack et al., 1998). Finally, we should note that polybrominated diphenylethers (PBDEs, see margin) that, like the PBBs (see above), are used as flame retardants, are of increasing environmental concern (de Boer et al., 2000). 

Walters and Guiseppe-Elle [221] studied the sorption of 2,3,7,8-tetrachloro-dibenzo-p-dioxin to soils from aqueous methanol mixtures and evaluated the applicability of the cosolvent theory to such sorption. Sorption kinetics were influenced by the fraction of methanol in the liquid phase and the soil type. 

Cummings AM, Metcalf JL, Bimbaum L. 1996. Promotion of endometriosis by 2,3,7,8-tetrachloro-dibenzo-p-dioxin in rats and mice Time-dose dependence and species comparison. Toxicol Appl Pharmacol 138 131-139. 

DeCaprio AP, McMartin DM, O Keefe PW, et al. 1986. Subchronic oral toxicity of 2,3,7,8-tetrachloro-dibenzo-p-dioxin in the guinea pig Comparisons with a PCB-containing transformer fluid pyrolysate. Fundam Appl Toxicol 6 454-463. 

Gasiewicz TA, Rucci G. 1991. Alpha-naphthoflavone acts as an antagonist of 2,3,7,8-tetrachloro-dibenzo-p-dioxin by forming an inactive complex with the Ah receptor. Mol Pharmacol 40 607-612. 

Huuskonen H, Undila M, Pohjanvirta R, et al. 1994. Developmental toxicity of 2,3,7,8-tetrachloro-dibenzo-p-dioxin (TCDD) in the most TCDD-resistant and -susceptible rat strains. Toxicol Appl Pharmacol 124(2) 174-80. 

Lawrence BP, Kerkvliet NI. 1997. Role of altered arachidonic acid metabolism in 2,3,7,8-tetrachloro-dibenzo-p-dioxin-induced immune suppression in C57BI/6 mice. Toxicol Sci 42 13-22. 

Lucier GW, Tritscher A, Goldsworthy T, et al. 1991. Ovarian hormones enhance 2,3,7,8-tetrachloro-dibenzo-p-dioxin-mediated increases in cell proliferation and preneoplastic foci in a two-stage model for rathepatocarcinogenesis. Cancer Res 51 1391-1397. 

Mocarelli P, Needham LL, Marocchi A, et al. 1991. Serum concentrations of 2,3,7,8-tetrachloro-dibenzo-p-dioxin and test results from selected residents of Seveso, Italy. J Toxicol Environ Health 32 357-366. 

Poland A, Knutson JC (1982), Ann. Rev. Pharmacol. Toxicol. 22 517-554., 2,3,7,8-tetrachloro-dibenzo-p-dioxin and related halogenated aromatic hydrocarbons examination of the mechanism of toxicity"... 

Thielen DR, Olsen G (1988), Anal. Chem. 60 1332-1336.. .Optimization of alumina selectivity for tetrachlorodibenzo-p-dioxins and the isomer-specific determination of 2,3,7,8-tetrachloro-dibenzo-p-dioxin ... 

The most toxic PCDD is 2,3,7,8-tetrachloro-dibenzo-p-dioxin. Draw the structure of this compound. Also draw the structures of two other isomers containing four chlorine atoms. 

Cl1 HI804 (R)-2-cyc ohexyl succinic acid-1-methyl ester 220498-07-7 25.00 1.0640 2 23153 C12H4CI402 2,3,7,8-tetrachloro-dibenzo-p-dioxin 1746-01-6 25.00 1.5843 2... 

The Seveso disaster began on July 10, 1976 at the Industrie Chimiche Meda Societa Azionaria (ICMESA) chemical plant in Meda, Italy. This event became internationally known as the Seveso disaster, after the name of the most severely affected community. An increase in pressure due to an exothermic reaction in a 2,4,5-trichlorophenol-production reactor caused the rupture disk of the safety valve to burst. About 3000 kg of chemicals were released into the air. The release included 2,4,5-trichlorophenol, used in the manufacture of herbicides, and possibly up to 30 kg of the dioxin TCDD (2,3,7,8-tetrachloro-dibenzo-p-dioxin). Dioxin first came to widespread public notice during the Vietnam War, when it was identified as a component of the defoliant Agent Orange. Dioxin has also been considered to be the most toxic human-made substance. 

Alsharif NZ, Grandjean CJ, Murray WJ, Stohs SJ. 1990. 2,3,7,8-Tetrachloro-dibenzo-p-dioxin (TCDD)-induced decrease in the fluidity of rat liver membranes. Xenobiotica 20 979-88... 

Lee CA, Lawrence BP, Kerkvliet NI, Rifkind AB. 1998. 2,3,7,8-Tetrachloro-dibenzo-p-dioxin induction of cytochrome P450-dependent arachidonic acid metabolism in mouse liver microsomes ... 

Kouri RE, Rude TH, Joglekar R, et al. 1978. 2,3,7,8-Tetrachloro-dibenzo-p-dioxin as cocarcinogen causing 3- methylcholanthrene initiated subcutaneous tumors in mice genetically nonresponsive at Ah locus. Cancer Res 38 2777-2783. 

J. S. Murray, P. Evans, and P. Politzer, Int.. Quantum Chem., 37, 271 (1990). A Comparative Analysis of the Electrostatic Potentials of Some Structural Analogues of 2,3,7,8-Tetrachloro-dibenzo-p-dioxin and of Related Aromatic Systems. 

WHO-TEF and Relative Toxicity Factors to 2,3,7,8-Tetrachloro-dibenzo-p-dioxin Values for a Few Non-orffio and Mono-ortho Substituted PCBs... 

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