1746-01-6

White crystals or tan crystalline powder.

2,3,7,8-TETRACHLORODIBENZO-P-DIOXIN (TCDD)(1746-01-6) reaacts when exposed to ultraviolet light in solution in isooctane or n-octanol. Undergoes catalytic perchlorination .

Insoluble in water.

TCDD is primarilly a research chemical. As noted above, TCDD is an inadvertent contaminant in herbicide precursors and thus in the herbicides themselves. It is also formed during various combustion processes including the incineration of chemical wastes (chlorophenols, chlorinated benzenes, and biphenyl ethers). It may be found in flue gases, fly ash, and soot particles. It is highly persistent in soil, and contamination may be retained for years. TCDD is the most toxic of all the dioxins, and has the potential for bio-accumulation in animals. Thus, it is applied in herbicide formulations, but is not used per se. It has been estimated that approximately 2 million acres in the United States have been treated for weed control on one or more occasions with approximately 15 million pounds of TCDD contaminated 2,4,5,-T, 2,4,-D, or combinations of the two.

Literature sources indicate that this chemical is nonflammable.

Move victim to fresh air. Call 911 or emergency medical service. Give artificial respiration if victim is not breathing. Do not use mouth-to-mouth method if victim ingested or inhaled the substance; give artificial respiration with the aid of a pocket mask equipped with a one-way valve or other proper respiratory medical device. Administer oxygen if breathing is difficult. Remove and isolate contaminated clothing and shoes. In case of contact with substance, immediately flush skin or eyes with running water for at least 20 minutes. For minor skin contact, avoid spreading material on unaffected skin. Keep victim warm and quiet. Effects of exposure (inhalation, ingestion, or skin contact) to substance may be delayed. Ensure that medical personnel are aware of the material(s) involved and take precautions to protect themselves. Medical observation is recommended for 24-48 hours after breathing overexposure, as pulmonary edema may be delayed. As first aid for pulmonary edema, a doctor or authorized paramedic may consider administering a drug or other inhalation therapy.

Decomposes in ultraviolet (UV) light.

The term dioxins refers to chlorinated hydrocarbons containing a dibenzo-p-dioxin structure (two benzene rings conjoined at their para carbons by two oxygen molecules). The nomenclature for chlorinated dibenzodioxins (CDD) is based on the number and position of the chlorine molecules and include mono- (MCDD), di- (DCDD), tri- (TrCDD), tetra- (TCDD), penta- (PeCDD), hexa- (HxCDD), hepta- (HpCDD), and octachlorinated (OCDD) congeners. There are 75 congeners in total. The 2,3,7,8-tetrachlorodienzo-p-dioxin (2,3,7,8-TCDD) congener is the most familiar congener due in part to its toxicity in animal models, its widespread distribution and persistence in the environment, its bioaccumulation potential, and because most data pertain to this congener. Dioxins in pure form are colorless solids and are formed as combustion products. Dioxins may be formed during the combustion of organic material in the presence of halogens, especially chlorine (and bromine), during waste incineration and forest fires. They also occur as contaminants in herbicides.
Dioxin was a contaminant of Agent Orange and possibly responsible for some of the adverse health effects associated with exposure to the defoliant. Dioxin was the poisoning agent in a high-profile political incident in 2004. Dioxin was ultimately identified as the cause of the disfiguring acne-like skin (chloracne) condition suffered by Ukrainian opposition leader Viktor Yushchenko a few months prior to the first presidential election. The suspicion was that the dioxin was placed into soup consumed by Mr Yushchenko. The acne-like skin condition is a recognized hallmark of dioxin poisoning in humans. The actual intake of dioxin in this incident is unknown.

Tetrachlorodibenzo-p-dioxin is a white, needleshaped, crystalline solid.

White Solid

A toxic polychlorinated dibenzo-p-dioxin detected in domestic meat and poultry.

With the exception of its use in research, it is ironic that there are no known uses for any of the dioxins. They are unintended byproducts of chemical manufacturing and combustion. There is no commercial manufacture of these compounds. The limited production of dioxins for use in research involves production by condensation of polychlorophenol or, for a specific dioxin, by chlorination of the parent dibenzo-p-dioxin.

ChEBI: 2,3,7,8-tetrachlorodibenzodioxine is a polychlorinated dibenzodioxine.

2,3,7,8-TCDD is not commercially produced except for its use as a research chemical. 2,3,7,8-TCDDis a contaminant of 2,4,5-trichlorophenol (2,4,5-TCP), the herbicide 2-(2,4,5- trichlorophenoxy)propionic acid [Silvex], the herbicide 2,4,5-trichlorophenoxyacetic acid (2,4,5-T), the wood preservative pentachlorophenol, hexachlorophene, hexachlorobenzene, and polychlorodiphenyl ethers. 2,3,7,8-TCDD is also produced by incineration of municipal, hospital, and toxic wastes and sludges and wood that contain chlorinated compounds and materials, of polyvinylchloride containing plastics, by paper and pulp bleaching, during PCB electrical transformer fires, during the hot processes of dye and pigment manufacturing, and smelter emissions.
It is not imported into the United States. The major source of 2,3,7,8-TCDDwas in the manufacture of 2,4,5-trichlorophenoxyacetic acid (2,4,5-T), which was introduced in the late 1940s. Prior to 1965, commercial 2,4,5-T contained up to 30 mg/kg (ppm) 2,3,7,8-TCDD but it was reduced to 0.01 ppm in the mid-1980s. Its use peaked in the 1970s, and has been phased out in Europe and the United States. The levels of 2,3,7,8-TCDD in the Vietnam War herbicide Agent Orange (1:1 mixture of the n-butyl esters of 2,4,5-T and (2,4-dichlorophenoxy)acetic acid (2,4-D)) varied considerably from 0.02 to 47 mg/kg (ppm). In the 1960s, the level of 2,3,7,8-TCDD could have been as high as 100 mg/kg in Agent Orange. In the 1980s, all producers claimed that 2,3,7,8-TCDD concentrations were less than 0.1 mg/kg.
2,3,7,8-TCDD and other PCDDs are formed by hot industrial, thermal, and photochemical processes that involve chlorinated organics.

Chlorinated dibenzo-p-dioxins (CDDs) cause chloracne, may cause hepatotoxicity, immunotoxicity, reproductive toxicity, developmental toxicity, and central nervous system toxicity, and are considered to be a human carcinogen.
The most obvious health effect in humans for exposure to CDDs is chloracne, a severe skin disease characterized by follicular hyperkeratosis (comedones) occurring with or without cysts and pustules.2–4 Unlike adolescent acne, chloracne may affect almost every follicle in an involved area, and it may be more disfiguring than adolescent acne.

TCDD and other chlorinated dibenzodioxins, dibenzofurans, and planar PCBs are thought to operate through a common mechanism. For humans and rodents, there is an initial binding to the aryl hydrocarbon (Ah) receptor. Binding to the receptor is a necessary (but not sufficient) event for the biological response. TCDD induces many responses, including induction of gene expression, altered metabolism, altered cell growth and differentiation, and disruption of steroid hormone and growth factor signal transduction pathways. The very diversity of tissue-selective and species-selective responses elicited by TCDD requires that the receptor (Ah) is part of a multicomponent system, and it is unlikely that the differences in dose-response are related solely to differences in Ah receptor concentrations or affinities in various species or tissues (29). It is considered that there is an inducible protein-binding site in the liver (30,31) known as CYP1A1 (30–34) because TCDD was not sequestered in the liver of transgenic mice that lack P450 1A2 gene.

2,3,7,8-Tetrachlorodibenzo-p-dioxin (TCDD) is known to be a human carcinogen based on sufficient evidence of carcinogenicity from studies in humans, both epidemiological and on the mechanism of carcinogenesis. TCDD was first listed in the Second Annual Report on Carcinogens as reasonably anticipated to be a human carcinogen. Subsequently, a number of studies were published that examined cancer in human populations exposed to TCDD occupationally or through industrial accidents. A concerted research effort examined the molecular and cellular events that occur in tissues of humans and animals exposed to TCDD. Based on the new information, the listing was revised to known to be a human carcinogen in the January 2001 addendum to the Ninth Report on Carcinogens.

Although not produced commercially, TCDD is formed as a by-product in the synthesis of 2,4,5-trichlorophenol. TCDD was found in 85% of soil samples obtained from a trichlorophenol manufacturing site. Concentrations ranged from approximately 20 ng/kg to 600 g/kg (Van Ness et al., 1980). TCDD may be present in the herbicide 2,4-D which contains a mixture of dichloro-, trichloro-, and tetrachlorodioxins. TCDD is commonly found as a contaminant associated with pulp and paper mills (Boddington, 1990). In addition, during the manufacture of 2,4,5-T and silvex from trichlorophenol, TCDD was found at concentrations averaging 20 parts per billion (Newton and Snyder, 1978).
TCDD is unintentionally formed during the combustion of domestic and industrial waste (Czuczwa and Hites, 1984, 1986) and bleaching of paper pulp by chlorine compounds (Buser et al., 1989; Swanson et al., 1988).
Drinking water standard (final): MCLG: zero; MCL: 3 x 10^-5 μg/L (U.S. EPA, 2000). In Canada, the Ontario Ministry of Environment has established an Interim Drinking Water Objective of 10 parts per quadrillion (Boddington, 1990). In addition, the U.S. EPA (2000) recommended a DWEL of 4 x 10^-5 μg/L.

Biological. After a 30-d incubation period, the white rot fungus Phanerochaete chrysosporium was capable of oxidizing TCDD to carbon dioxide. Mineralization began between the third and sixth day of incubation. The production of carbon dioxide was highest between 3 to 18 d of incubation, after which the rate of a carbon dioxide produced decreased until the 30th day. It was suggested that the metabolism of TCDD and other compounds, including p,p′-DDT, benzo[a]pyrene, and lindane, was dependent on the extracellular lignin-degrading enzyme system of this fungus (Bumpus et al., 1985).
A half-life of 418 d was calculated based on die away test data (Kearney et al., 1971). In a laboratory sediment-water system incubated under anaerobic conditions, the half-life of TCDD was 500 to 600 d (Ward and Matsumura, 1978).
Soil. In shallow and deep soils, reported half-lives were 10 and 100 yr, respectively (Nauman and Schaum, 1987). Due to its low aqueous solubility, TCDD will not undergo significant leaching by runoff (Helling et al., 1973).
Surface Water. Plimmer et al. (1973) reported that the photolysis half-life of TCDD in a methanol solution exposed to sunlight was 3 h. Volatilization half-lives of 32 and 16 d were reported for lakes and rivers, respectively (Podoll et al., 1986).
Photolytic. Pure TCDD did not photolyze under UV light. However, in aqueous solutions containing cationic (1-hexadecylpyridinium chloride), anionic (sodium dodecyl sulfate), and nonionic (methanol) surfactants, TCDD decomposed into the end product tentatively identified as 2-phenoxyphenol. The times required for total TCDD decomposition using the cationic, anionic, and nonionic solutions were 4, 8, and 16 h, respectively (Botré et al., 1978). TCDD photodegrades rapidly in alcoholic solutions by reductive dechlorination. In water, however, the reaction was very slow (Crosby et al., 1973). In an earlier study, Crosby et al. (1971) reported a photolytic halflife of 14 d when TCDD in distilled water was exposed to sunlight. The major photodegradative pathway of TCDD involves a replacement of the chlorine atom by a hydrogen atom. The proposed degradative pathway is TCDD to 2,7,8-trichlorodibenzo[b,e][1,4]dioxin to 2,7-dichlorodibenzo- [b,e][1,4]dioxin to 2-chlorodibenzo[b,e][1,4]dioxin to dibenzo[b,e][1,4]dioxin to 2-hydroxydiphenyl ether, which undergoes polymerization (Makino et al., 1992).
Chemical/Physical. TCDD was dehalogenated by a solution of poly(ethylene glycol), potassium carbonate, and sodium peroxide. After 2 h at 85 °C, >99.9% of the applied TCDD decomposed. Chemical intermediates identified include tri-, di-, and chloro[b,e]dibenzo[1,4]dioxin, dibenzodioxin, hydrogen, carbon monoxide, methane, ethylene, and acetylene (Tundo et al., 1985).
TCDD will not hydrolyze to any reasonable extent (Kollig, 1993).

Absorption. TCDD is retained in all tissues. The highest retention is in fat and liver. Penetration values into human skin are low. For example, a dose of 6.5 ng/cm2 in acetone gave a rate of 5 g/cm2/h. Transfer to the fetus has been observed (43). Absorption rates after single dose in the diet were 50 to 70–90% (44–48). Rates in rats were lower (50–60%) when administered in the diet for more than 6 weeks (49), compared with a single-dose absorption rate of 70% (46).
Distribution. The major storage sites are liver and adipose tissue. The skin can act as an important storage site, and high concentrations can also be found in the adrenals (1). After one day of exposure for rats, mice, hamsters and guinea pigs, 25–70% of the dose was stored in the liver (41).
Excretion. Excretion is mostly fecal. Breast milk can be a route of elimination. Whole body half-lives were from 17 to 31 days in rat studies (46–52). Mice had lower halflives (53,54). Female rhesus monkeys with four years of dietary exposure had a longer half-life (391 days) (55,56). These half-lives are very fast considering human half-lives of 5.8–11.3 years (cited earlier).

Acetone (110 mg/L), benzene (570 mg/L), chlorobenzene (720 mg/L) chloroform (370 mg/L), o-dichlorobenzene (1,400 mg/L), methanol (10 mg/L) and octanol (48–50 mg/L) (Crummett and Stehl, 1973; Arthur and Frea, 1989); benzene (570 mg/L), tetrachloroethene (680 mg/L), lard oil (40 mg/L), hexane (280 mg/L) (quoted, Keith and Walters, 1992).

Acetone (110 mg/L), benzene (570 mg/L), chlorobenzene (720 mg/L) chloroform (370 mg/L), o-dichlorobenzene (1,400 mg/L), methanol (10 mg/L) and octanol (48–50 mg/L) (Crummett and Stehl, 1973; Arthur and Frea, 1989); benzene (570 mg/L), tetrachloroethene (680 mg/L), lard oil (40 mg/L), hexane (280 mg/L) (quoted, Keith and Walters, 1992).

Mortality
Mortality occurs after several days to weeks of exposure. Toxic effects observed in all animal species are progressive loss of body weight, reduced intake of food, atrophy of the thymus, gastrointestinal hemorrhage, and delayed lethality (17,18).
Skin
Skin effects are exhibited by humans and non human primates and are not modeled by laboratory animals, although some experimentation has been performed with hairless mice.
Cachexia
All mammalian species show body weight loss and reduced intake of food. Studies by Pohjanvirta and Tuomisto (19) indicated that TCDD may suppress the formation of hunger-related signals. A serotonergic mechanism was proposed because of increased levels of tryptophan and its metabolites, serotonin and 5-hydroxyindoleacetic acid, in blood and brain.
Endocrine effects
A variety of hormone systems are involved with exposure to TCDD, specifically, sex steroids, corticosteroids, and thyroid hormones. A target organ for TCDD is the pituitary gland where normal feedback mechanisms are disrupted (20).
Immunological Effects
Immunological effects are observed in mammals but are probably without relevance for humans.