Heptachlorodibenzo-p-dioxin

Last updated
Heptachlorodibenzo-p-dioxin
Heptachlorodibenzodioxin.svg
Names
Preferred IUPAC name
1,2,3,4,6,7,8-Heptachlorooxanthrene
Other names
  • 1,2,3,4,6,7,8-Heptachlorodibenzo-para-dioxin
  • 1,2,3,4,6,7,8-HpCDD
Identifiers
3D model (JSmol)
ChEBI
ChemSpider
ECHA InfoCard 100.223.051 OOjs UI icon edit-ltr-progressive.svg
EC Number
  • 694-835-3
KEGG
PubChem CID
UNII
UN number 2811
  • InChI=1S/C12HCl7O2/c13-2-1-3-10(7(17)4(2)14)21-12-9(19)6(16)5(15)8(18)11(12)20-3/h1H
    Key: WCLNVRQZUKYVAI-UHFFFAOYSA-N
  • C1=C2C(=C(C(=C1Cl)Cl)Cl)OC3=C(O2)C(=C(C(=C3Cl)Cl)Cl)Cl
Properties
C12HCl7O2
Molar mass 425.29 g·mol−1
AppearanceOff-white powder
1.9 x 10−3 mg/L
Hazards
GHS labelling:
GHS-pictogram-exclam.svg GHS-pictogram-silhouette.svg GHS-pictogram-pollu.svg
Danger
H319, H335, H341, H410
P201, P202, P261, P264, P271, P273, P280, P281, P304+P340, P305+P351+P338, P308+P313, P312, P337+P313, P391, P403+P233, P405, P501
Except where otherwise noted, data are given for materials in their standard state (at 25 °C [77 °F], 100 kPa).

1,2,3,4,6,7,8-Heptachlorodibenzo-para-dioxin (often referred to as 1,2,3,4,6,7,8-HpCDD) is a polychlorinated derivative of dibenzo-p-dioxin and can therefore be categorized as polychlorinated dibenzo-p-dioxin (PCDD), a subclass of dioxins which includes 75 congeners. HpCDD is the dibenzo-p-dioxin which is chlorinated at positions 1, 2, 3, 4, 6, 7, and 8. It is a polycyclic heterocyclic organic compound, since HpCDD contains multiple cyclic structures (two benzene rings connected by a 1,4-dioxin ring) in which two different elements (carbon and oxygen) are members of its rings. [1] HpCDD has molecular formula C12HCl7O2 and is an off-white powder, which is insoluble in water. [2]

Contents

History

Dioxins are mostly by-products of industrial processes such as the manufacturing of pesticides, bleaching of paper pulp or combustion processes such as waste incineration. [3] This means that heptachlorodibenzo-p-dioxin does not have a common use. In 1998, Professor Sharon Beder argued that large companies have tried to play down the seriousness of the toxic problems of dioxin. She described her concern in her paper ‘The Dioxin Controversy: Spilling over into Schools’. [4] Companies responded by stating that Beder’s paper was based on ‘fear and emotion’ and not on science. [5]

Metabolism

The halflife of heptachlorodibenzo-p-dioxin is calculated to be 3.6 years. This estimation was based on the analysis of fat tissue biopsies collected with an interval of 28 months from on 14-year-old girl who for a period of about 2–3 years had been exposed to technical pentachlorophenol. The half-lives of Hexachlorodibenzo-p-dioxin and octachlorodibenzo-p-dioxin were estimated to be 3.5 and 2 years, respectively. [6]

The effects of chlorodibenzo-p-dioxin exposure was examined in rats over a 13-week period. Hepatic accumulation was associated with alterations of several biochemical parameters. The following alterations were discovered: Ethoxyresorufin-O-deethylase activity was elevated 40-fold over controls; total cytochrome p450 content doubled and exhibited a 2 nanometer blue shift in the Soret maximum for the reduced hemoprotein-CO complex. Cytochrome p450c and cytochrome p450d were significantly increased, while cytochrome p450b levels were unaltered. Nearly all the dioxincongeners present in liver were represented by octachlorodibenzo-p-dioxin, with a slight amount of heptachlorinated-p-dioxin. [7]

Mechanism of action

Dioxins in general are able to bind to the AH receptor. This cell protein initiates effects of most of dioxin-like chemicals. The exact function of the protein of the cell is unknown, but the protein plays a role in rhythmic functions and organ development.

When a dioxin enters the cell and binds to the AH receptor, a complex is formed with another protein, ARNKT [ dubious ]. This heterodimer (which is in fact a transcription factor) binds to the DNA. The complex can inhibit or activate unknown genes. [8]

Toxicity

Chloracne, an acne-like eruption of blackheads, cysts, and pustules, is associated with exposure to pentachlorophenol contaminated with heptachlorodibenzo-p-dioxin. This association was first made when individuals employed in the manufacturing of pentachlorophenol were examined. It was discovered that direct contact with the pentachlorophenol lead to significantly increased risk of cloracne. [9] More human studies on the toxicity of heptachlorodibenzo-p-dioxin are not available. However, animal studies showed non-human toxicity levels: LD50 rabbit, oral > 5000 mg/kg, LD50 rat, oral > 5000 mg/kg, [10] and LD50 guinea pig, oral > 600 ug/kg. [11]

Heptachlorodibenzo-p-dioxin is not classifiable as to its carcinogenicity to humans. [12]

The abiothic degradation of heptachlorodibenzo-p-dioxin has been estimated. The rate constant for the vapor phase reaction of heptachlorodibenzo-p-dioxin with photochemically produced hydroxyl radicals has been estimated to be 1.3x10−12 cu cm/molecule-sec at 25 °C which corresponds to an atmospheric half-life of 12.3 days at an atmospheric concentration of 5x105 hydroxyl radicals per cu cm. [13]

Adverse effects

The known adverse effects for dioxin compounds are (as previously mentioned) carcinogenicity. Furthermore, chloroacne, disturbances in tooth development and other developmental effects at high concentration are known adverse effects of HpCDD. There is a very wide range of health effects because the mechanism can have all sorts of implications on the genome (see mechanism of action). HpCDD is known to cause lung cancer and anemia in rats. [14] However, there are not many studies on humans that assess the health risk factors of HpCDD. HpCDD seems to be more potent once it is circulating the body in comparison with other PCDD’s, [15] making it more toxic than other PCDD’s. This probably has to do with the high substitution of chloro groups. Dioxins in general are hard to break down efficiently. This causes bioaccumulation and environmental persistence. [16]

Effects on animals

Immunotoxicity

HpCDD is known to suppress the antibody response of C57B1/6 mice to sheep erythrocytes, a macrophage and T-cell-dependent antigen. In vivo approaches have been applied to characterize the sensitivity of suppression of the antibody response of C57B1/6 mice by an acute oral exposure to HpCDD. Suppression of the antibody response was observed after HpCDD administration at various times prior to or following antigen challenge. [17]

Carcinogenicity

HpCDD is indicated as a potent liver tumor promotor in female (and only female) rats. In primary cultures of hepatocytes of female rats, co-mitogenic actions of HpCDD and congeners are mediated by the aryl-hydrocarbon (AH) receptor. These actions are enhanced by estrogens. HpCDD alone is relatively ineffective in the promotion of tumors in female rats livers, but when DNA-synthesis is stimulated by epidermal growth factor, HpCDD acts as a co-mitogen. These effects are observed for different congeners of polychlorinated dibenzo-p-dioxins, based on their affinity with the aryl-hydrocarbon receptor. [18]

Related Research Articles

<span class="mw-page-title-main">Polychlorinated biphenyl</span> Chemical compound

Polychlorinated biphenyls (PCBs) are highly carcinogenic chemical compounds, formerly used in industrial and consumer products, whose production was banned in the United States by the Toxic Substances Control Act in 1979 and internationally by the Stockholm Convention on Persistent Organic Pollutants in 2001. They are organic chlorine compounds with the formula C12H10−xClx; they were once widely used in the manufacture of carbonless copy paper, as heat transfer fluids, and as dielectric and coolant fluids for electrical equipment.

Polychlorinated dibenzodioxins (PCDDs), or simply dioxins, are a group of long-lived polyhalogenated organic compounds that are primarily anthropogenic, and contribute toxic, persistent organic pollution in the environment.

Polybrominated diphenyl ethers or PBDEs, are a class of organobromine compounds that are used as flame retardants. Like other brominated flame retardants, PBDEs have been used in a wide array of products, including building materials, electronics, furnishings, motor vehicles, airplanes, plastics, polyurethane foams, and textiles. They are structurally akin to polychlorinated diphenyl ethers (PCDEs), polychlorinated biphenyls (PCBs) and other polyhalogenated compounds, consisting of two halogenated aromatic rings. PBDEs are classified according to the average number of bromine atoms in the molecule. The health hazards of these chemicals have attracted increasing scrutiny, and they have been shown to reduce fertility in humans at levels found in households. Because of their toxicity and persistence, the industrial production of some PBDEs is restricted under the Stockholm Convention, a treaty to control and phase out major persistent organic pollutants (POPs).

Benzo(<i>a</i>)pyrene Carcinogenic compound found in smoke and soot

Benzo[a]pyrene (BaP or B[a]P) is a polycyclic aromatic hydrocarbon and the result of incomplete combustion of organic matter at temperatures between 300 °C (572 °F) and 600 °C (1,112 °F). The ubiquitous compound can be found in coal tar, tobacco smoke and many foods, especially grilled meats. The substance with the formula C20H12 is one of the benzopyrenes, formed by a benzene ring fused to pyrene. Its diol epoxide metabolites (more commonly known as BPDE) react with and bind to DNA, resulting in mutations and eventually cancer. It is listed as a Group 1 carcinogen by the IARC. In the 18th century a scrotal cancer of chimney sweepers, the chimney sweeps' carcinoma, was already known to be connected to soot.

<span class="mw-page-title-main">Pentachlorophenol</span> Chemical compound

Pentachlorophenol (PCP) is an organochlorine compound used as a pesticide and a disinfectant. First produced in the 1930s, it is marketed under many trade names. It can be found as pure PCP, or as the sodium salt of PCP, the latter of which dissolves easily in water. It can be biodegraded by some bacteria, including Sphingobium chlorophenolicum.

<span class="mw-page-title-main">Dibenzo-1,4-dioxin</span> Chemical compound

Dibenzo-1,4-dioxin, also dibenzodioxin or dibenzo-p-dioxin (dibenzo-para-dioxin), is a polycyclic heterocyclic organic compound in which two benzene rings are connected by a 1,4-dioxin ring. Its molecular formula is C12H8O2. The two oxygen atoms occupy opposite (para-) positions in the six-membered dioxin ring.

<span class="mw-page-title-main">Dibenzofuran</span> Chemical compound

Dibenzofuran is a heterocyclic organic compound with the chemical structure shown at right. It is an aromatic compound that has two benzene rings fused to a central furan ring. All the numbered carbon atoms have a hydrogen atom bonded to each of them. It is a volatile white solid that is soluble in nonpolar organic solvents. It is obtained from coal tar, where it exists as a 1% component.

<span class="mw-page-title-main">Sudan I</span> Chemical compound

Sudan I is an organic compound, typically classified as an azo dye. It is an intensely orange-red solid that is added to colourise waxes, oils, petrol, solvents, and polishes. Sudan I has also been adopted for colouring various foodstuffs, especially curry powder and chili powder, although the use of Sudan I in foods is now banned in many countries, because Sudan I, Sudan III, and Sudan IV have been classified as category 3 carcinogens by the International Agency for Research on Cancer. Sudan I is still used in some orange-coloured smoke formulations and as a colouring for cotton refuse used in chemistry experiments.

Substances, mixtures, and exposure circumstances in this list have been classified as group 1 by the International Agency for Research on Cancer (IARC): The agent (mixture) is carcinogenic to humans. The exposure circumstance entails exposures that are carcinogenic to humans. This category is used when there is sufficient evidence of carcinogenicity in humans. Exceptionally, an agent (mixture) may be placed in this category when evidence of carcinogenicity in humans is less than sufficient but there is sufficient evidence of carcinogenicity in experimental animals and strong evidence in exposed humans that the agent (mixture) acts through a relevant mechanism of carcinogenicity.

<i>o</i>-Toluidine Aryl amine

o-Toluidine (ortho-toluidine) is an organic compound with the chemical formula CH3C6H4NH2. It is the most important of the three isomeric toluidines. It is a colorless liquid although commercial samples are often yellowish. It is a precursor to the herbicides metolachlor and acetochlor.

<span class="mw-page-title-main">1,4-Dioxin</span> Chemical compound

1,4-Dioxin (also referred as dioxin or p-dioxin) is a heterocyclic, organic, non-aromatic compound with the chemical formula C4H4O2. There is an isomeric form of 1,4-dioxin, 1,2-dioxin (or o-dioxin). 1,2-Dioxin is very unstable due to its peroxide-like characteristics.

<span class="mw-page-title-main">Polychlorinated dibenzofurans</span> Family of organic compounds

Polychlorinated dibenzofurans (PCDFs) are a family of organic compounds with one or several of the hydrogens in the dibenzofuran structure replaced by chlorines. For example, 2,3,7,8-tetrachlorodibenzofuran (TCDF) has chlorine atoms substituted for each of the hydrogens on the number 2, 3, 7, and 8 carbons. Polychlorinated dibenzofurans with chlorines at least in positions 2,3,7 and 8 are much more toxic than the parent compound dibenzofurane, with properties and chemical structures similar to polychlorinated dibenzodioxins. These groups together are often inaccurately called dioxins. They are known developmental toxicants, and suspected human carcinogens. PCDFs tend to co-occur with polychlorinated dibenzodioxins (PCDDs). PCDFs can be formed by pyrolysis or incineration at temperatures below 1200 °C of chlorine containing products, such as PVC, PCBs, and other organochlorides, or of non-chlorine containing products in the presence of chlorine donors. Dibenzofurans are known persistent organic pollutants (POP), classified among the dirty dozen in the Stockholm Convention on Persistent Organic Pollutants.

<span class="mw-page-title-main">Octachlorodibenzodioxin</span> Chemical compound

Octachlorodibenzodioxin is one of polychlorinated dibenzodioxins (PCDDs).

<span class="mw-page-title-main">Dioxins and dioxin-like compounds</span> Class of chemical compounds

Dioxins and dioxin-like compounds (DLCs) are a group of chemical compounds that are persistent organic pollutants (POPs) in the environment. They are mostly by-products of burning or various industrial processes or, in the case of dioxin-like PCBs and PBBs, unwanted minor components of intentionally produced mixtures.

Chlorinated polycyclic aromatic hydrocarbons (Cl-PAHs) are a group of compounds comprising polycyclic aromatic hydrocarbons with two or more aromatic rings and one or more chlorine atoms attached to the ring system. Cl-PAHs can be divided into two groups: chloro-substituted PAHs, which have one or more hydrogen atoms substituted by a chlorine atom, and chloro-added Cl-PAHs, which have two or more chlorine atoms added to the molecule. They are products of incomplete combustion of organic materials. They have many congeners, and the occurrences and toxicities of the congeners differ. Cl-PAHs are hydrophobic compounds and their persistence within ecosystems is due to their low water solubility. They are structurally similar to other halogenated hydrocarbons such as polychlorinated dibenzo-p-dioxins (PCDDs), dibenzofurans (PCDFs), and polychlorinated biphenyls (PCBs). Cl-PAHs in the environment are strongly susceptible to the effects of gas/particle partitioning, seasonal sources, and climatic conditions.

<span class="mw-page-title-main">2,3,7,8-Tetrachlorodibenzodioxin</span> Polychlorinated dibenzo-p-dioxin, chemical compound

2,3,7,8-Tetrachlorodibenzo-p-dioxin (TCDD) is a polychlorinated dibenzo-p-dioxin (sometimes shortened, though inaccurately, to simply 'dioxin') with the chemical formula C12H4Cl4O2. Pure TCDD is a colorless solid with no distinguishable odor at room temperature. It is usually formed as an unwanted product in burning processes of organic materials or as a side product in organic synthesis.

Toxic equivalency factor (TEF) expresses the toxicity of dioxins, furans and PCBs in terms of the most toxic form of dioxin, 2,3,7,8-TCDD. The toxicity of the individual congeners may vary by orders of magnitude.

Persistent, bioaccumulative and toxic substances (PBTs) are a class of compounds that have high resistance to degradation from abiotic and biotic factors, high mobility in the environment and high toxicity. Because of these factors PBTs have been observed to have a high order of bioaccumulation and biomagnification, very long retention times in various media, and widespread distribution across the globe. Most PBTs in the environment are either created through industry or are unintentional byproducts.

<span class="mw-page-title-main">2,2',3,3',4,4'-Hexachlorobiphenyl</span> Chemical compound

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Indeno(1,2,3-<i>cd</i>)pyrene Polycyclic aromatic hydrocarbon

Indeno[1,2,3-cd]pyrene is a polycyclic aromatic hydrocarbon (PAH), one of 16 PAHs generally measured in studies of environmental exposure and air pollution. Many compounds of this class are formed when burning coal, oil, gas, wood, household waste and tobacco, and can bind to or form small particles in the air. The compounds are known to have toxic, mutagenic and/or carcinogenic properties. Over 100 different PAHs have been identified in environmental samples. One of these 16 is Indeno[1,2,3-cd]pyrene (IP). IP is the combination of an indeno molecule and a pyrene molecule with a fluoranthene network. In 1962, the National Cancer Institute reported that indeno[1,2,3-cd]pyrene has a slight tumor activity. This was confirmed in 1973 by the IARC in mice testing.

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