2,3,7,8-tetrachlorodibenzo-£-dioxin toxicity

Dong, W., H. Teraoka, K. Yamazaki, S. Tsukiyama, S. Imani, T. Imagawa, J.J. Stegeman, R.E. Peterson and T. Hiraga. 2,3,7,8-tetrachlorodibenzo-/)-dioxin toxicity in the zebrafish embryo local circulation failure in the dorsal midbrain is associated with increased apoptosis. Toxicol. Sci. 69 191-201, 2002. 

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

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. 

Tietge, J.E., R.D. Johnson, K.M. Jensen, P.M. Cook, G.E. Elonen, J.D. Fernandez, G.W. Holcombe, D.B. Lothenbach, and J.W. Nichols. 1998. Reproductive toxicity and disposition of 2,3,7,8-tetrachlorodibenzo--dioxin in adult brook trout (Salvelinus fontinalis) following a dietary exposure. Environ. Toxicol. Chem. 17 2395-2407. 

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-/)-dioxin increased incidence of cleft palate in mice. Toxicol. Appl. Pharmacol. 77 292-302. 

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. 

Data are available suggesting that DEHP might act as an antagonist for the hepatic damage caused by other chemicals. DEHP was combined with 2,3,7,8-tetrachlorodibenzo-/ -dioxin (TCDD) to determine if the hypolipidemic effects of DEHP could counteract the hyperlipidemic effects of the TCDD (Tomaszewski et al. 1988). Pretreatment with DEHP mitigated many of the toxic effects of TCDD. 

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. 

Perhaps the most renowned example is the extensively-used 2,4,5-T (2,4,5-trichlorophenoxyacetic acid), or rather the 2,3,7,8-tetrachlorodibenzo- -dioxin (TCDD) impurity which sometimes accompanies it. During massive use of the herbicide as a defoliant in the Vietnam war, TCDD was found almost by accident to be one of the most toxic synthetic substances ever tested. Soon, it was shown to be present in domestic 2,4,5-T as well as in the chemical warfare agents. Tests in laboratory animals demonstrated that some of the observed levels indeed were quite high enough to cause toxic effects (32). 

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. 

These compounds have been much in the news, mainly because of the extreme toxicity of the congener 2,3,7, 8-tetrachlorodibenzo-/ -dioxin (TCDD), usually called dioxin in the news media. Like the PCBs, PCDDs and PCDFs are families with many congeners there are 75 PCDDs and 135 PCDFs (Figure 12). 

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... 

Some immunotoxicants suppress all the specific immune functions by binding to the Ah receptors on lymphoid cells. Highly toxic dioxin (2,3,7,8-tetrachlorodibenzo- -dioxin) is an example of such toxicants. However, most immunotoxicants exhibit more restricted activities. For example, some heavy metals, such as lead and mercury, suppress humoral and cell-mediated host resistance. Similarly, some carbamate pesticides depress antibody response and phagocytosis, while cyclosporine primarily impairs the B cells. 

The toxicity of these compounds is species dependent. The most toxic is 2,3,7,8-tetrachlorodibenzo--dioxin. 

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).]... 

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