2,3,7,8-Tetrachlorodibenzo-p-dioxin toxicity

Fanelb, R., M.P. Bertoni, M.G. Castelli, C. Chiabrando, G.P. Martelh, A. Noseda, S. Garattini, C. Binaghi, V. Marazza, and F. Pezza. 1980b. 2,3,7,8-Tetrachlorodibenzo-p-dioxin toxic effects and tissue levels in animals from the contaminated area of Seveso, Italy. Arch. Environ. Contam. Toxicol. 9 569-577. 

Spitsbergen, J.M., J.M. Kleeman, and R.E. Peterson. 1988b. 2,3,7,8-Tetrachlorodibenzo-p-dioxin toxicity in yellow perch (Perea flavescens). Jour. Toxicol. Environ. Health 23 359-383. 

Prasch AL, Tanguay RE, Mehta V, Heideman W, Peterson RE (2006) Identification of zebrafish ARNTl homologs 2,3,7,8-tetrachlorodibenzo-p-dioxin toxicity in the developing zebrafish requires ARNTl. Mol Pharmacol 69 776-787... 

Leonards, P.E.G., de Vries, T.H., Minnaard, W., Stuijfzand, S., de Voogt, P., Cofino, W.P, van Straalen, N.M., van Hattum, B. (1995). Assessment of experimental data on PCB-induced reproduction inhibition in mink, based on an isomer- and congener-specific approach using 2,3,7,8-tetrachlorodibenzo-p-dioxin toxic equivalency. Environ Toxicol Chem 14(4) 639-652. 

Kleeman, J.M., J.R. Olson, and R.E. Peterson. 1988. Species differences in 2,3,7,8-tetrachlorodibenzo-p-dioxin toxicity and biotransformation in fish. Eundament. Appl. Toxicol. 10 206-213. 

Canga L, Levi R, Rifkind AB. 1988. Heart as a target organ in 2,3,7,8-tetrachlorodibenzo-p-dioxin toxicity Decreased -adrenergic responsiveness and evidence of increased intracellular calcium. Proc Natl Acad Sci USA 85 905-909. 

Tomaszewski KE, Montgomery CA, Melnick RL. 1988. Modulation of 2,3,7,8-tetrachlorodibenzo -p-dioxin toxicity inF344 rats by di(2-ethylhexyl) phthalate. Chem Biol Interact 65 205-222. 

Teraoka, H., W. Dong, S. Ogawa, S. Tsukiyama, Y. Okuhara, M. Niiyama, N. Ueno, R.E. Peterson and T. Hiraga. 2,3,7,8-Tetrachlorodibenzo-p-dioxin toxicity in the zebrafish embryo altered regional blood flow and impaired lower jaw development. Toxicol. Sci. 65 192-199, 2002. 

Bunger, M.K., S.M. Moran, E. Glover, T.L. Thomae, G.P. Lahvis, B.C. Lin and C.A. Bradfield. Resistance to 2,3,7,8-tetrachlorodibenzo-p-dioxin toxicity and abnormal liver development in mice carrying a mutation in the nuclear localization sequence of the aryl hydrocarbon receptor. J. Biol. Chem. 278 17767-17774, 2003. 

Bunger MK, Glover E, Moran SM, Walisser JA, Lahvis GP, Hsu EL, Bradfield CA (2008) Atmormal liver developmait and resistance to 2, 3, 7, 8-tetrachlorodibenzo-p-dioxin toxicity in mice carrying a mutation in the DNA-binding domain of the aryl hydrocarbon receptor. Toxicol Sci 106 83—92... 

Eernandez-Salguero, P.M., Hilbert, D.M., Rudikoff, S. et al. (1996). Aryl-hydrocarbon receptor-deficient mice are resistant to 2,3,7,8-tetrachlorodibenzo-p-dioxin-induced toxicity. Toxicology and Applied Pharmacology 140, 173-179. 

Variations in the manufacturing process of 2,4,5-trichloro- and pentachlorophenol (but not 2,4-dichlorophenol) have sometimes resulted in contamination of the product by small amounts of heterocyclic impurities (4,5). Of these, the chlorinated dibenzo-p-dioxins such as TCDD (2,3,7,8-tetrachlorodibenzo-p-dioxin) have received much scientific and public attention because of their real or potential toxicity 6, 7), [Chick edema factor, a curious toxicological problem to poultry producers for several years, has been shown to be composed of chlorodibenzo-p-dioxins (8).]... 

Tetrachlorodibenzo-p-dioxin (TCDD) (I), an occasional contaminant in 2,4,5-T and other trichlorophenol derivatives, is the most toxic of the commonly-encountered dioxins (8) and it received most of our attention. Its low solubility in common solvents and water (ca. 2 ppb) limited our experiments since the products were difficult to identify by the conventional techniques of organic chemistry. However, TCDD has an absorption maximum at 307 nm in methanol—well within the solar spectrum observed at the earth s surface and near the region of maximum intensity (310-330 nm) of the UV lamps used in previous experiments (H 29). 

Studies on the chlorodibenzodioxins have led to the following conclusions (1) 2,7-dichlorodibenzo-p-dioxin and octachlorodibenzo-p-di-oxin have a low acute toxicity (2) 2,3,7,8-tetrachlorodibenzo-p-dioxin has an unusually high toxicity (3) hexachlorodibenzo-p-dioxin is highly toxic but less toxic than 2,3,7,8-tetrachlorodibenzo-p-dioxin (4) all chlorodibenzodioxins are not alike in their toxicological properties. Isomers of the same dibenzo-p-dioxin vary in toxicological properties, making it important to identify them specifically. 

TAetection of the highly potent impurity, 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) in the herbicide 2,4,5-trichlorophenoxyacetic acid (2,4,5-T), necessitated an environmental assessment of the impact of this contaminate. Information was rapidly needed on movement, persistence, and plant uptake to determine whether low concentrations reaching plants, soils, and water posed any threat to man and his environment. Because of the extreme toxicity of TCDD, utmost precautions were taken to reduce or minimize the risk of exposure to laboratory personnel. Synthesis of uniformly labeled C-TCDD by Muelder and Shadoff (I) greatly facilitated TCDD detection in soil and plant experiments. For unlabeled experiments it seemed wise to use only small quantities of diluted solutions in situations where decontamination was feasible and to rely on the sensitivity afforded by electron capture gas chromatography... 

The preparation of 2,3,7,8-tetrachlorodibenzo-p-dioxin by chlorination of 2,7-dichlorodibenzo-p-dioxin yields a product containing significant quantities of trichloro- and pentachlorodibenzo-p-dioxins (11). Such mixtures are not amenable to separation on a preparative scale. Although 2,3,7,8-tetrachlorodibenzo-p-dioxin has been prepared by the pyrolytic condensation of sodium 2,4,5-trichlorophenate, this method is undesirable for preparation of 2,3,7,8-tetrachlorodibenzo-p-dioxin on the gram scale (2, 12). The pyrolytic reaction is difficult to control and the potential danger is enhanced by the product s toxicity. The salt was dissolved in bEEE [bis(2-ethoxyethyl) ether, bp 189°-190°C] and refluxed for 15 hours with the Ullmann catalyst. The desired product was obtained in 39% yield by condensation of potassium 2,4,5-trichlorophenate (Reaction 3). 

In addition to its extremely high oral toxicity, skin contact with substances containing 2,3,7,8-tetrachlorodibenzo-p-dioxin may allow toxicity in the form of chloracne, a condition characterized by eruptions of the skin on the face, neck, and back. Also, chlorinated dibenzo-p-dioxins have been associated with the chick edema factor, a disease of chicks associated with contaminated fats or oils used in the manufacture of their feed. 

Since 1950 many in the chemical industry have been keenly aware of the possibilities of highly toxic 2,3,7,8-tetrachlorodibenzo-p-dioxin forming in the manufacture of 2,4,5-trichlorophenol. This phenol is made by treating 1,2,4,5-tetrachlorobenzene with strong caustic at high temperatures for several hours. Manufacturing procedures which do not carefully control temperature and alkalinity increase the probability of dioxin formation. 

The pollutants characteristic of the industry wastewaters are summarized in Table 5.4 through Table 5.11, for both classical and toxic pollutants. The toxic pollutant data have been developed using a verification protocol established by U.S. EPA, with the exception of the following selenium, silver, thallium, and 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCCD). Table 5.12 presents the minimum detection limit for the toxic pollutants. Any value below the minimum limit is listed in the summary tables as below detection limit (BDL). 

Poland, A., and J. C. Knutson. 1982. 2,3,7,8-Tetrachlorodibenzo-p-dioxin and Related Halogenated Aromatic Hydrocarbons Examination of the Mechanism of Toxicity. Ann. Rev. Pharmacol. Toxicol. 22, 517. 

Data from Kociba, R.J. and B.A. Schwetz. 1982b. A review of the toxicity of 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) with a comparison to the toxicity of other chlorinated dioxin isomers. 

Birnbaum, L.S., H. Weber, M.W. Harris, J.C. Lamb IV, and J.D. McKinney. 1985. Toxic interaction of specific polychlorinated biphenyls and 2,3,7,8-tetrachlorodibenzo-p-dioxin increased incidence of cleft palate in mice. Toxicol. Appl. Pharmacol. 77 292-302. 

Hochstein, J.R., R.J. Aulerich, and S.J. Bursian. 1988. Acute toxicity of 2,3,7,8-tetrachlorodibenzo-p-dioxin to mink. Arch. Environ. Contam. Toxicol. 17 33-37. 

Johnson, R.D., J.E. Tietge, K.M. Jensen, J.D. Fernandez, A.L. Linnum, D.B. Lothenbach, G.W. Holcombe, P.M. Cook, S.A. Christ, D.L. Lattier, and D.A. Gordon. 1998. Toxicity of 2,3,7,8-tetrachlorodibenzo-p-dioxin to early life stage brook trout (Salvelinus fontinalis) following parental dietary exposure. Environ. Toxicol. Chem. 17 2408-2421. 

Miller, R.A., L.A. Norris, and C.L. Hawkes. 1973. Toxicity of 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) in aquatic organisms. Environ. Health Perspec. 5 177-186. 

Olson, J.R., M.A. Holscher, and R.A. Neal. 1980a. Toxicity of 2,3,7,8-tetrachlorodibenzo-p-dioxin in the golden Syrian hamster. Toxicol. Appl. Pharmacol. 55 67-78. 

Prince, R. and K.C. Cooper. 1995a. Comparisons of the effects of 2,3,7,8-tetrachlorodibenzo-p-dioxin on chemically impacted and nonimpacted subpopulations of Fundulus heteroclitus I. TCDD toxicity. Environ. Toxicol. Chem. 14 579-587. 

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