Dioxins toxicology

There is increasing interest in the relationship of the HS response to environmental toxicology. As induction of the HS response portends resistance to otherwise lethal stresses, many environmental hazards have the potential for inducing the HS response (Finnell et al., 1992). Activity of the dioxin receptor is affected by HS proteins (Nemoto et al., 1990 Pongratz et al., 1992) and it is likely that the HS... 

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. 

Garrison, P.M., Tullis, K., and Aarts J.M.M.J.G. et al. (1996). Species specific recombinant cell lines as bioassay systems for the detection of dioxin-like chemicals. Fundamental and Applied Toxicology 30, 194-203. 

Powell, W.R., Bright, S., and Bello, S.M. (2000). Developmental and tissue-specific expression of AHRl, AHR2, and ARNT2 in dioxin-sensitive and -resistant populations of the marine fish—Fundulus heteroclitus. Toxicological Sciences 57, 229-239. 

Stronkhurst, J., Leonards, P., and Murk, A.J. (2002). Using the dioxin receptor Calux in vitro assay to screen marine harhour sediments for a dioxin-hke mode of action. Environmental Toxicology and Chemistry 21, 2552-2561. 

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).]... 

Oevere toxicological responses have been associated with certain chloro- dibenzodioxins. One of these responses is chloracne, a folliculosis first associated with skin contamination by chlorohydrocarbons in 1899 (3). Serious outbreaks of chloracne-like lesions associated with runaway reactions in the production of 2,4,5-trichlorophenol occurred in Germany in the early 1950 s (5). 2,4,5-Trichlorophenol itself does not cause acne (S), but the contaminants which may be formed in the uncontrolled production of 2,4,5-trichlorophenol are extremely potent acnegens (5). 2,3,7,8-Tetrachlorodibenzo-p-dioxin and tri- and tetra-... 

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. 

Chlorinated dibenzo-ip-dioxins were prepared on the gram scale for use as toxicological standards, 2,7-Dichlorodi-henzo-p-dioxin was prepared by catalytic condensation of potassium 2-bromo-4-chlorophenate in 70% yield. Thermal condensation of the potassium salt of 2,4,4 -trichloro-2 -hydroxy diphenyl ether gave a mixture of the 2,8- and 2,7-dichlorodibenzo-p-dioxins which were separated by fractional recrystallization. 2,3,7,8-T etrachlorodibenzo-p-dioxin of 99.9- -% purity was prepared by catalytic condensation of potassium 2,4,5-trichlorophenate. An isomeric mixture of hexachlorodibenzo-p-dioxins was prepared by pyrolytic condensation of sodium 2,3,4,6-tetrachlorophenate. Chlorination of pentachlorophenol (containing < 0.07% tetrachlorophenol) in trichlorobenzene gave octachlorodi-benzo-p-dioxin in 80% yield contaminated by 5-15% heptachlorodibenzo-p-dioxin. Oxidative methods were used to produce octachlorodibenzo-p-dioxin at 99.9% purity. 

Information is also needed on the toxicological interactions of groups of polychlorinated chemicals (such as certain biphenyls, biphenylenes, and dibenzofurans) known to be isosteric with 2,3,7,8-TCDD and that frequently coexist with 2,3,7,8-TCDD in environmental samples. Acquisition of these data should provide the basis of a risk assessment analysis for dioxin and fishery and wildlife resources. 

Cattebeni, F., A. Cavallaro, and G. Galli (eds.). 1978. Dioxin Toxicological and Chemical Aspects. Spectrum Publ., New York. 222 pp. 

Helder, T. 1981. Effects of 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) on early life stages of rainbow trout (Salmo gairdneri, Richardson). Toxicology 19 101-112. 

U.S. Public Health Service (USPHS). 1998. Toxicological profile for chlorinated dibenzo-p-dioxins (update). U.S. Dept. Health Human Serv., Agen. Toxic Subst. Dis. Regis. 709 pp. 

Smith, L.S., T.R. Schwartz, K. Felz, and T.J. Kubiak. 1990. Determination and occurrence of AHH-active polychlorinated biphenyls, 2,3,7,8-tetrachloro-/>-dioxin and 2,3,7,8-tetrachlorodibenzofuran in Lake Michigan sediment and biota. The question of their relative toxicological significance. Chemosphere 21 1063-1085. 

Zeytun, A., et. al., Analysis of 2,3,7,8-tetrachlorodibenzo-p-dioxin-induced gene expression profile in vivo using pathway-specific cDNA arrays, Toxicology, 178, 241, 2002. 

Sulentic, C., et. al., Interactions at a dioxin responsive element (DRE) and an overlapping kappaB site within the hs4 domain of the 3 alpha immunoglobulin heavy chain enhancer, Toxicology, 200, 235, 2004. 

Nohara, K., et.al., The effects of perinatal exposure to low doses of 2,3,7,8-tetrachlorod-ibenzo-p-dioxin on immune organs in rats, Toxicology, 154, 123, 2000. 

Gehrs, B. and Smialowicz, R., Persistent suppression of delayed-type hypersensitivity in adult F344 rats after perinatal exposure to 2,3,7,8-tetrachlorodibenzo-p-dioxin, Toxicology, 134, 79,1999. 

In the USA, the National Toxicology Program has declared dioxin a known human carcinogen - but injection moulder Brevet Inc. (who manufactures medical devices from PVC) plans to challenge the action in court. Brief details are given here. 

Polychlorinated dibenzo-p-dioxins, polychlorinated dibenzofurans and ortho-unsubstituted polychlorinated biphenyls (non-ortho polychlorobiphenyls) are three structurally and toxicologically related families of anthropogenic chemical compounds that have in recent years been shown to have the potential to cause serious environmental contamination due to their extreme toxicity [77-82], These substances are trace-level components or byproducts in several large-volume and widely used synthetic chemicals, principally polychlorobiphenyls and... 

The majority of scientific and governmental concerns for the hazards of these compounds have been directed toward analytical methodologies, toxicology, epidemiology and determination of the disposition in the environment of the single most toxic isomer, 2,3,7,8-tctrachlorodibenzo-p-dioxin [77-82, 84],... 

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