Polychlorinated dibenzodioxins

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General structure of PCDDs where n and m can range from 0 to 4 PCDD general structure.png
General structure of PCDDs where n and m can range from 0 to 4

Polychlorinated dibenzodioxins (PCDDs), or simply dioxins, are a group of polyhalogenated organic compounds that are significant environmental pollutants.


They are commonly but inaccurately referred to as dioxins for simplicity, because every PCDD molecule contains a dibenzo-1,4-dioxin skeletal structure, with 1,4-dioxin as the central ring. Members of the PCDD family bioaccumulate in humans and wildlife because of their lipophilic properties, and may cause developmental disturbances and cancer.

Dioxins occur as by-products in the manufacture of some organochlorides, in the incineration of chlorine-containing substances such as polyvinyl chloride (PVC), in the chlorine bleaching of paper, and from natural sources such as volcanoes and forest fires. [1] There have been many incidents of dioxin pollution resulting from industrial emissions and accidents; the earliest such incidents were in the mid 19th century during the Industrial Revolution. [2]

The word "dioxins" may also refer to other similarly acting chlorinated compounds (see Dioxins and dioxin-like compounds).

Chemical structure of dibenzo-1,4-dioxins

The skeletal formula and substituent numbering scheme of the parent compound dibenzo-1,4-dioxin Dibenzo-p-dioxin-numbering-2D-skeletal.png
The skeletal formula and substituent numbering scheme of the parent compound dibenzo-1,4-dioxin

The structure of dibenzo-1,4-dioxin consists of two benzene rings joined by two oxygen bridges. This makes the compound an aromatic diether. The name dioxin formally refers to the central dioxygenated ring, which is stabilized by the two flanking benzene rings.

In PCDDs, chlorine atoms are attached to this structure at any of 8 different places on the molecule, at positions 1–4 and 6–9. There are 75 different PCDD congeners (that is, related dioxin compounds). [3]

The toxicity of PCDDs depends on the number and positions of the chlorine atoms. Congeners that have chlorine in the 2, 3, 7, and 8 positions have been found to be significantly toxic. In fact, 7 congeners have chlorine atoms in the relevant positions which were considered toxic by the World Health Organization toxic equivalent (WHO-TEQ) scheme. [4]

Historical perspective

Structure of 2,3,7,8-tetrachlorodibenzodioxin (TCDD) 2,3,7,8-tetrachlorodibenzo(b,e)(1,4)dioxine 200.svg
Structure of 2,3,7,8-tetrachlorodibenzodioxin (TCDD)

Low concentrations of dioxins existed in nature prior to industrialization as a result of natural combustion and geological processes. [5] [6] Dioxins were first unintentionally produced as by-products from 1848 onwards as Leblanc process plants started operating in Germany. [2] The first intentional synthesis of chlorinated dibenzodioxin was in 1872. Today, concentrations of dioxins are found in all humans, with higher levels commonly found in persons living in more industrialized countries. The most toxic dioxin, 2,3,7,8-tetrachlorodibenzodioxin (TCDD), became well known as a contaminant of Agent Orange, a herbicide used in the Malayan Emergency and the Vietnam War. [7] Later, dioxins were found in Times Beach, Missouri [8] and Love Canal, New York [9] and Seveso, Italy. [10] More recently, dioxins have been in the news with the poisoning of President Viktor Yushchenko of Ukraine in 2004, [11] the Naples Mozzarella Crisis [12] the 2008 Irish pork crisis, and the German feed incident of 2010. [13]

Sources of dioxins

The United States Environmental Protection Agency inventory of sources of dioxin-like compounds is possibly the most comprehensive review of the sources and releases of dioxins, [14] but other countries now have substantial research as well.

Concentration profile of PCDD in a dated sediment core from Esthwaite Water, Cumbria, UK PCDD sediment core.svg
Concentration profile of PCDD in a dated sediment core from Esthwaite Water, Cumbria, UK

Occupational exposure is an issue for some in the chemical industries, historically for those making chlorophenols or chlorophenoxy acid herbicides or in the application of chemicals, notably herbicides. In many developed nations there are now emissions regulations which have dramatically decreased the emissions [14] and thus alleviated some concerns, although the lack of continuous sampling of dioxin emissions causes concern about the understatement of emissions. In Belgium, through the introduction of a process called AMESA, continuous sampling showed that periodic sampling understated emissions by a factor of 30 to 50 times. Few facilities have continuous sampling.

Dioxins are produced in small concentrations when organic material is burned in the presence of chlorine, whether the chlorine is present as chloride ions or as organochlorine compounds, so they are widely produced in many contexts. According to the most recent US EPA data, the major sources of dioxins are broadly in the following types: [14]

When first carried out in 1987, the original US EPA inventory of dioxin sources revealed that incineration represented more than 80% of known dioxin sources. As a result, US EPA implemented new emissions requirements. These regulations succeeded in reducing dioxin stack emissions from incinerators. Incineration of municipal solid waste, medical waste, sewage sludge, and hazardous waste together now produce less than 3% of all dioxin emissions. Since 1987, however, backyard barrel burning has showed almost no decrease, and is now the largest source of dioxin emissions, producing about one third of the total output. [14]

In incineration, dioxins can also reform or form de novo in the atmosphere above the stack as the exhaust gases cool through a temperature window of 600 to 200 °C. The most common method of reducing the quantity of dioxins reforming or forming de novo is through rapid (30 millisecond) quenching of the exhaust gases through that 400 °C window. [15] Incinerator emissions of dioxins have been reduced by over 90% as a result of new emissions control requirements. Incineration in developed countries is now a very minor contributor to dioxin emissions.

Dioxins are also generated in reactions that do not involve burning — such as chlorine bleaching fibers for paper or textiles, and in the manufacture of chlorinated phenols, particularly when reaction temperature is not well controlled. [16] Compounds involved include the wood preservative pentachlorophenol, and also herbicides such as 2,4-dichlorophenoxyacetic acid (or 2,4-D) and 2,4,5-trichlorophenoxyacetic acid (2,4,5-T). Higher levels of chlorination require higher reaction temperatures and greater dioxin production. Dioxins may also be formed during the photochemical breakdown of the common antimicrobial compound triclosan. [17]

Sources of human intake

A chart illustrating how much dioxin the average American consumes per day. (Note: pg = picogram, or one trillionth of a gram, or 10 g). Dioxin chart.png
A chart illustrating how much dioxin the average American consumes per day. (Note: pg = picogram, or one trillionth of a gram, or 10 g).

Tolerable daily, monthly or annual intakes have been set by the World Health Organization and a number of governments. Dioxins enter the general population almost exclusively from ingestion of food, specifically through the consumption of fish, meat, and dairy products since dioxins are fat-soluble and readily climb the food chain. [18] [19]

Children are passed substantial body burdens by their mothers, and breastfeeding increases the child's body burden. [20] Dioxin exposure can also occur from contact with Pentachlorophenol (Penta) treated lumber as Pentachlorophenol often contains dioxins as a contaminant. Children's daily intakes during breast feeding are often many times above the intakes of adults based on body weight. This is why the WHO consultation group assessed the tolerable intake so as to prevent a woman from accumulating harmful body burdens before her first pregnancy. [21] Breast fed children usually still have higher dioxin body burdens than non breast fed children. The WHO still recommends breast feeding for its other benefits. [22] In many countries dioxins in breast milk have decreased by even 90% during the two last decades. [23]

Dioxins are present in cigarette smoke. [24] Dioxin in cigarette smoke was noted as "understudied" by the US EPA in its "Re-Evaluating Dioxin" (1995). In that same document, the US EPA acknowledged that dioxin in cigarettes is "anthropogenic" (man-made, "not likely in nature").


Dioxins are absorbed primarily through dietary intake of fat, as this is where they accumulate in animals and humans. In humans, the highly chlorinated dioxins are stored in fatty tissues and are neither readily metabolized nor excreted. The estimated elimination half-life for highly chlorinated dioxins (4–8 chlorine atoms) in humans ranges from 4.9 to 13.1 years. [25]

The persistence of a particular dioxin congener in an animal is thought to be a consequence of its structure. Dioxins with no lateral (2, 3, 7, and 8) chlorines, which thus contain hydrogen atoms on adjacent pairs of carbons, can more readily be oxidized by cytochromes P450.[ citation needed ] The oxidized dioxins can then be more readily excreted rather than stored for a long time.[ citation needed ]


Space-filling model of 2,3,7,8-tetrachlorodibenzodioxin Dioxin-3D-vdW.png
Space-filling model of 2,3,7,8-tetrachlorodibenzodioxin

2,3,7,8-Tetrachlorodibenzodioxin (TCDD) is considered the most toxic of the congeners (for the mechanism of action, see 2,3,7,8-Tetrachlorodibenzodioxin and Aryl hydrocarbon receptor). Other dioxin congeners including PCDFs and PCBs with dioxin-like toxicity, are given a toxicity rating from 0 to 1, where TCDD = 1 (see Dioxins and dioxin-like compounds). This toxicity rating is called the Toxic Equivalence Factor concept, or TEF. TEFs are consensus values and, because of the strong species dependence for toxicity, are listed separately for mammals, fish, and birds. TEFs for mammalian species are generally applicable to human risk calculations. The TEFs have been developed from detailed assessment of literature data to facilitate both risk assessment and regulatory control. [4] Many other compounds may also have dioxin-like properties, particularly non-ortho PCBs, one of which has a TEF as high as 0.1.

The total dioxin toxic equivalence (TEQ) value expresses the toxicity as if the mixture were pure TCDD. The TEQ approach and current TEFs have been adopted internationally as the most appropriate way to estimate the potential health risks of mixture of dioxins. Recent data suggest that this type of simple scaling factor may not be the most appropriate treatment for complex mixtures of dioxins; both transfer from the source and absorption and elimination vary among different congeners, and the TEF value is not able to accurately reflect this. [26]

Dioxins and other persistent organic pollutants (POPs) are subject to the Stockholm Convention. The treaty obliges signatories to take measures to eliminate where possible, and minimize where not possible to eliminate, all sources of dioxin.

Health effects in humans

Chloracne on the ear and neck of a herbicide production worker Chloracne-in-herbicide-worker.png
Chloracne on the ear and neck of a herbicide production worker

Dioxins build up primarily in fatty tissues over time (bioaccumulation), so even small exposures may eventually reach dangerous levels. In 1994, the US EPA reported that dioxins are a probable carcinogen, but noted that non-cancer effects (reproduction and sexual development, immune system) may pose a greater threat to human health. TCDD, the most toxic of the dibenzodioxins, is classified as a Group 1 carcinogen by the International Agency for Research on Cancer (IARC). TCDD has a half-life of approximately 8 years in humans, although at high concentrations, the elimination rate is enhanced by metabolism. [27] The health effects of dioxins are mediated by their action on a cellular receptor, the aryl hydrocarbon receptor (AhR). [28]

Exposure to high levels of dioxins in humans causes a severe form of persistent acne, known as chloracne. [29] High occupational or accidental levels of exposures to dioxins have been shown by epidemiological studies to lead to an increased risk of tumors at all sites. [30] Other effects in humans (at high dose levels) may include:

Recent studies have shown that high exposure to dioxins changes the ratio of male to female births among a population such that more females are born than males. [38]

Dioxins accumulate in food chains in a fashion similar to other chlorinated compounds (bioaccumulation). This means that even small concentrations in contaminated water can be concentrated up a food chain to dangerous levels because of the long biological half life and low water solubility of dioxins.

Toxic effects in animals

While it has been difficult to establish specific health effects in humans due to the lack of controlled dose experiments, studies in animals have shown that dioxin causes a wide variety of toxic effects. [39] In particular, TCDD has been shown to be teratogenic, mutagenic, carcinogenic, immunotoxic, and hepatotoxic. Furthermore, alterations in multiple endocrine and growth factor systems have been reported. The most sensitive effects, observed in multiple species, appear to be developmental, including effects on the developing immune, nervous, and reproductive systems. [40] The most sensitive effects are caused at body burdens relatively close to those reported in humans.

Among the animals for which TCDD toxicity has been studied, there is strong evidence for the following effects:

In rodents, including rats, [41] mice, [42] hamsters and guinea pigs, [43] birds, [44] and fish. [45]
In rodents [41] [46] and fish [47]
In rodents, [46] chickens, [48] and fish [49]
In rodents [40] and fish [50]
In rodents [51] and fish. [52]

The LD50 of dioxin also varies wildly between species with the most notable disparity being between the ostensibly similar species of hamster and guinea pig. The oral LD50 for guinea pigs is as low as 0.5 to 2 μg/kg body weight, whereas the oral LD50 for hamsters can be as high as 1 to 5 mg/kg body weight, a difference of as much as thousandfold or more, and even among rat strains there may be thousandfold differences. [39]

Agent Orange

U.S. Army Huey helicopter spraying Agent Orange over Vietnamese agricultural land US-Huey-helicopter-spraying-Agent-Orange-in-Vietnam.jpg
U.S. Army Huey helicopter spraying Agent Orange over Vietnamese agricultural land

Agent Orange was the code name for one of the herbicides and defoliants the U.S. military used as part of its herbicidal warfare program, Operation Ranch Hand, during the Vietnam War from 1961 to 1971. It was a mixture of 2,4,5-T and 2,4-D. The 2,4,5-T used was contaminated with 2,3,7,8-tetrachlorodibenzodioxin (TCDD), an extremely toxic dioxin compound.

During the Vietnam war, between 1962 and 1971, the United States military sprayed 20,000,000 U.S. gallons (76,000,000 L) of chemical herbicides and defoliants in Vietnam, eastern Laos and parts of Cambodia, as part of Operation Ranch Hand. [53]

By 1971, 12% of the total area of South Vietnam had been sprayed with defoliating chemicals, which were often applied at rates that were 13 times as high as the legal USDA limit. [54] In South Vietnam alone, an estimated 10 million hectares of agricultural land were ultimately destroyed. [55] In some areas, TCDD concentrations in soil and water were hundreds of times greater than the levels considered safe by the U.S. Environmental Protection Agency. [56] [57]

According to Vietnamese Ministry of Foreign Affairs, 4.8 million Vietnamese people were exposed to Agent Orange, resulting in 400,000 people being killed or maimed, and 500,000 children born with birth defects. [58] The Red Cross of Vietnam estimates that up to 1 million people are disabled or have health problems due to Agent Orange contamination. [59] The United States government has challenged these figures as being unreliable and unrealistically high. [60] [61]

Dioxin exposure incidents

Dioxin testing

The analyses used to determine these compounds' relative toxicity share common elements that differ from methods used for more traditional analytical determinations. The preferred methods for dioxins and related analyses use high resolution gas chromatography/mass spectrometry (HRGC/HRMS). Concentrations are determined by measuring the ratio of the analyte to the appropriate isotopically labeled internal standard. [86]

Also novel bio-assays like DR CALUX are nowadays used in identification of dioxins and dioxin-like compounds. The advantage in respect to HRGC/HRMS is that it is able to scan many samples at lower costs. Also it is able to detect all compounds that interact with the Ah-receptor which is responsible for carcinogenic effects. [87]

See also

Related Research Articles

Polychlorinated biphenyl

A polychlorinated biphenyl (PCB) is an organic chlorine compound with the formula C12H10−xClx. Polychlorinated biphenyls were once widely deployed as dielectric and coolant fluids in electrical apparatus, carbonless copy paper and in heat transfer fluids.

The Seveso disaster was an industrial accident that occurred around 12:37 PM on July 10, 1976, in a small chemical manufacturing plant approximately 20 kilometres (12 mi) north of Milan in the Lombardy region of Italy. It resulted in the highest known exposure to 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) in residential populations, which gave rise to numerous scientific studies and standardized industrial safety regulations. The EU industrial safety regulations are known as the Seveso II Directive. This accident was ranked eighth in a list of the worst man-made environmental disasters by Time magazine in 2010.


Chloracne is an acne-like eruption of blackheads, cysts, and pustules associated with exposure to certain halogenated aromatic compounds, such as chlorinated dioxins and dibenzofurans. The lesions are most frequently found on the cheeks, behind the ears, in the armpits and groin region.

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 the 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. Their chlorine analogs are polychlorinated diphenyl ethers (PCDEs). 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).

The term flame retardants subsumes a diverse group of chemicals which are added to manufactured materials, such as plastics and textiles, and surface finishes and coatings. Flame retardants are activated by the presence of an ignition source and are intended to prevent or slow the further development of ignition by a variety of different physical and chemical methods. They may be added as a copolymer during the polymerisation process, or later added to the polymer at a moulding or extrusion process or applied as a topical finish. Mineral flame retardants are typically additive while organohalogen and organophosphorus compounds can be either reactive or additive.

Persistent organic pollutants (POPs), sometimes known as "forever chemicals" are organic compounds that are resistant to environmental degradation through chemical, biological, and photolytic processes. Because of their persistence, POPs bioaccumulate with potential adverse impacts on human health and the environment. The effect of POPs on human and environmental health was discussed, with intention to eliminate or severely restrict their production, by the international community at the Stockholm Convention on Persistent Organic Pollutants in 2001.

Xenoestrogens are a type of xenohormone that imitates estrogen. They can be either synthetic or natural chemical compounds. Synthetic xenoestrogens include some widely used industrial compounds, such as PCBs, BPA, and phthalates, which have estrogenic effects on a living organism even though they differ chemically from the estrogenic substances produced internally by the endocrine system of any organism. Natural xenoestrogens include phytoestrogens which are plant-derived xenoestrogens. Because the primary route of exposure to these compounds is by consumption of phytoestrogenic plants, they are sometimes called "dietary estrogens". Mycoestrogens, estrogenic substances from fungi, are another type of xenoestrogen that are also considered mycotoxins.

2,4,5-Trichlorophenoxyacetic acid

2,4,5-Trichlorophenoxyacetic acid, a synthetic auxin, is a chlorophenoxy acetic acid herbicide used to defoliate broad-leafed plants. It was developed in the late 1940s and was widely used in the agricultural industry until being phased out, starting in the late 1970s due to toxicity concerns. Agent Orange, a defoliant used by the British in the Malayan Emergency and the U.S. in the Vietnam War, was equal parts 2,4,5-T and 2,4-D. 2,4,5-T itself is toxic with a NOAEL of 3 mg/kg/day and a LOAEL of 10 mg/kg/day. Additionally, the manufacturing process for 2,4,5-T contaminates this chemical with trace amounts of 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD). TCDD is a carcinogenic persistent organic pollutant with long-term effects on the environment. With proper temperature control during production of 2,4,5-T, TCDD levels can be held to about .005 ppm. Before the TCDD risk was well understood, early production facilities lacked proper temperature controls and individual batches tested later were found to have as much as 60 ppm of TCDD.

PCB congener list

This is a complete list of polychlorinated biphenyl (PCB) congeners.


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.

Polychlorinated dibenzofurans

More thorough treatise of all groups with similar actions and binding to aryl hydrocarbon reeceptor is given in Dioxins and dioxin-like compounds.

Environmental toxicology

Environmental toxicology is a multidisciplinary field of science concerned with the study of the harmful effects of various chemical, biological and physical agents on living organisms. Ecotoxicology is a subdiscipline of environmental toxicology concerned with studying the harmful effects of toxicants at the population and ecosystem levels.


Octachlorodibenzodioxin is one of polychlorinated dibenzodioxins (PCDDs).

Dioxins and dioxin-like compounds

Dioxins and dioxin-like compounds (DLCs) are a group of chemical compounds that are persistent environmental pollutants (POPs). Some of them are highly toxic, but the toxicity among them varies 30,000-fold. They are grouped together, because their mechanism of action is the same. They activate aryl hydrocarbon receptor, albeit with very different binding affinities, leading to high differences in toxicity and other effects. They are mostly by-products of burning or various industrial processes - or, in case of dioxin-like PCBs and PBBs, unwanted minor components of intentionally produced mixtures. They include:

Polyhalogenated compounds (PHCs) are any compounds with multiple substitutions of halogens. They are of particular interest and importance because they bioaccumulate in humans, and comprise a superset of which has many toxic and carcinogenic industrial chemicals as members. PBDEs, PCBs, dioxins (PCDDs) and PFCs are all polyhalogenated compounds. They are generally non-miscible in organic solvents or water, but miscible in some hydrocarbons from which they often derive.

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.

2,3,7,8-Tetrachlorodibenzodioxin Polychlorinated dibenzo-p-dioxin, chemical compound

2,3,7,8-Tetrachlorodibenzo-p-dioxin (TCDD) is a polychlorinated dibenzo-p-dioxin with the chemical formula C
. 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. Majority of PBTs in the environment are either created through industry or are unintentional byproducts.


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. HpCDD has molecular formula C12HCl7O2 and is an off-white powder, which is insoluble in water.


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