1,2,3,4-tetrachlorodibenzo-p-dioxin

Structure— Function Relationships. Since PCBs and related HAHs are found in the environment as complex mixtures of isomers and congeners, any meaninghil risk and hazard assessment of these mixtures must consider the quaUtative and quantitative stmcture—function relationships. Several studies have investigated the stmcture—activity relationships for PCBs that exhibit 2,3,7,8-tetrachlorodibenzo-p-dioxin [1746-01-6] (1)... 

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. 

Chlorinated dibenzo ip-dioxins are contaminants of phenol-based pesticides and may enter the environment where they are subject to the action of sunlight. Rate measurements showed that 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) is more rapidly photolyzed in methanol than octachlorodi-benzo-p-dioxin. Initially TCDD yields 2,3,7-trichlorodiben-zo-p-dioxin, and subsequent reductive dechlorination is accompanied by ring fission. Pure dibenzo-p-dioxin gave polymeric material and some 2,2 -dihydroxybiphenyl on irradiation. Riboflavin-sensitized photolysis of the potential precursors of dioxins, 2,4-dichlorophenol and 2,4,5-trichloro-phenol, in water gave no detectable dioxins. The products identified were chlorinated phenoxyphenols and dihydroxy-biphenyls. In contrast, aqueous alkaline solutions of purified pentachlorophenol gave traces of octachlorodibenzo-p-dioxin on irradiation. 

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). 

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-... 

Acute Lethality. Samples of 2,7-dichlorodibenzo-p-dioxin, 2,3,7,8-tetrachlorodibenzo-p-dioxin, hexachlorodibenzo-p-dioxin, and octachloro-dibenzo-p-dioxin were evaluated for acute oral lethality in the following animals. 

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. 

Female Wistar rats treated orally with 0.125-16 jug/kg/day of 2,3,7,8-tetrachlorodibenzo-p-dioxin (8-D), 50-800 jug/kg/day of 1,2,3,4-tetra-chlorodibenzo-p-dioxin (4-D , and 250-2000 /xg/kg/day of 2,7-dichloro-dibenzo-p-dioxin (2-D) and 1,000-2,000 /xg/kg/day of 2,3-dichlorodi-benzo-p-dioxin or 2-chlorodibenzo-p-dioxin during 6—15 days of gestation (first morning of a positive vaginal smear was designated as day 1) were assessed for prenatal effects of the compounds on their progeny. 

Tetrachlorodibenzo-p-Dioxin (8-D). Prenatal Effects. Data from 2 experiments conducted with 0.125-16 / g/kg/day doses of... 

Oral treatment of pregnant dams with 0.25 /xg (or more) /kg/day of 2,3,7,8-tetrachlorodibenzo-p-dioxin for 10 days during gestation resulted in adverse effects on rat development. No adverse effects were seen at the 0.125 ju,g/kg/day. When C-2,3,7,8-tetrachlorodibenzo-p-dioxin (2.99 fjLc/mg) was given at 2 /xg/kg/day there was activity, primarily in liver and to a lesser extent, in fat and brain. When a single oral dose of 200 /Ag/kg was administered on gestation days 16, 17, or 18 and was followed 6 hours later with tissue sampling, the label was also observed in the fetus and placenta. Placenta had approximately twice as much label as the fetus. 

In male rats 2,3,7,8-tetrachlorodibenzo-p-dioxin induced hyperplastic changes and sperm granulomas in the epididymis, but no apparent lethal mutations were noted during post-meiotic phases of spermatogenesis. 

Rabbits, Applied to the Potent Acnegen, 2,3,7,8-Tetrachlorodibenzo-p-dioxin, /. Invest. Dermatol. (1962) 39, 511. 

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... 

Heat Stability of 2,3,7,8-Tetrachlorodibenzo- -dioxin. A sample boat containing 1-3 mg of 2,3,7,8-tetrachlorodibenzo-p-dioxin was placed in a Sargent Tube Heater (Model J-807) which contained a 1/2 inch i.d. quartz tube. Air was aspirated through the tube at a velocity of 0.02 ft/sec. This velocity gave a residence time of 21 sec. (Residence time was extended by connecting a second heater in series with the first.)... 

Stability of 2,3,7,8-Tetrachlorodibenzo- >-dioxin Towards Air Oxidation Under Simulated Conditions. Air was bubbled through two borosilicate glass gas absorption bottles equipped with fritted glass bubblers. The first bottle contained 1-octanol for presaturation of the air, and the second bottle contained 1-octanol solutions of the dioxin treated as follows (1) octanol only, (2) octanol mixed with 74-105ju, glass beads to increase the surface area, and (3) octanol mixed with magnesium oxide to simulate a basic soil. The original solution and the sample solutions were scanned with a UV spectrophotometer at various time intervals for 4 days to determine the stability of 2,3,7,8-tetrachlorodibenzo-p-dioxin. 

The heat stability of 2,3,7,8-tetrachlorodibenzo-p-dioxin is shown in Table II. The material is quite stable to 700°C with 50% decomposition obtained at this temperature. More than doubling the residence time resulted in only slightly more decomposition. However, decomposition of 2,3,7,8-tetrachlorodibenzo-p-dioxin is complete at 800°C. 

The half-life of the 2,3,7,8-tetrachlorodibenzo-p-dioxin in isooctane was estimated to be 40 min for the 0.5 meter exposure and 3 hours for the one meter exposure. The half-life in 1-octanol was essentially the same. The 24-hour photolysis products of the 2,3,7,8-tetrachlorodibenzo-p-dioxin were examined by gas chromatography. The smallest concentration of 2,3,7,8-tetrachlorodibenzo-p-dioxin that could be detected by the instrument was 0.5 ppm. When an injection of the 24-hour photolysis product was made, no tetra was detected. An additional confirmation of the disappearance of the 2,3,7,8-tetrachlorodibenzo-p-dioxin in the 24-hour photolysis products was obtained when thej yiaterial was submitted to the Chemical-Biology Research Laboratory for rabbit testing. No chloracnegenic activity was indicated. ... 

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