General structure of PCDDs where
n and
m can range from 0 to 4
Polychlorinated dibenzodioxins (PCDDs), or simply dioxins, are a group of organic polyhalogenated compounds that are significant environmental pollutants. They are commonly but inaccurately referred to as dioxins for simplicity, because every PCDD molecule contains a dioxin skeletal structure as the central ring. This gives the molecule a dibenzo-p-dioxin ring system. 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 organochlorines, in the incineration of chlorine-containing substances such as PVC (polyvinyl chloride), 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).
[edit] Chemical structure of dibenzo-p-dioxins
The structure of dibenzo-p-dioxin comprises 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 chlorines 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]
Structure of
2,3,7,8-tetrachlorodibenzo-p-dioxin (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-tetrachlorodibenzo-p-dioxin (TCDD), became well known as a contaminant of Agent Orange, a herbicide used in the Vietnam War.[7] To speed up chemical reactions, the U.S. manufacturers had increased the temperature in the process of preparation. This increased the concentration of TCDD many times more than other types of pesticides that were being used by U.S. farmers. 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 Irish pork crisis of 2008, and the German feed incident of 2010.[13]
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.
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]
- Combustion sources, e.g. municipal waste or medical waste incinerators and private backyard barrel burning
- Metal smelting
- Refining and process sources
- Chemical manufacturing sources
- Natural sources
- Environmental reservoirs
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 involed 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]
A chart illustrating how much dioxin the average American consumes per day. (Note: pg = picogram, or one trillionth of a gram, or 10
−12 g) .
[18]
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]
Most controversial is the United States Environmental Protection Agency (US EPA) assessment's (draft) finding that any reference dose that were to be set would be far below current average intakes. This is based on linear extrapolation model of cancer risk, which is not generally accepted for chemicals promoting cancer caused by other factors rather than initiating the cancer by itself.[20]
Children are passed substantial body burdens by their mothers, and breastfeeding increases the child's body burden.[21] 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.[22] 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.[23] In many countries dioxins in breast milk have decreased by even 90% during the two last decades.[24]
Dioxins are also in typical cigarette smoke.[25] 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.[26]
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]
2,3,7,8-Tetrachlorodibenzo-p-dioxin (TCDD) is considered the most toxic of the congeners (for the mechanism of action, see 2,3,7,8-Tetrachlorodibenzo-p-dioxin 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.[27]
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.
Dioxins build up primarily in fatty tissues over time (bioaccumulate), 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.[28] The health effects of dioxins are mediated by their action on a cellular receptor, the aryl hydrocarbon receptor (AhR).[29]
Exposure to high levels of dioxins in humans causes a severe form of persistent acne, known as chloracne.[30] 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.[31] 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.[39]
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.
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.[40] In particular, TCDD (see this) 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.[41] 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,[42] mice,[43] hamsters and guinea pigs,[44] birds,[45] and fish.[46]
- In rodents[42][47] and fish[48]
- Hepatotoxicity (liver toxicity)
- In rodents,[47] chickens,[49] and fish[50]
- In rodents[41] and fish[51]
- In rodents[52] and fish.[53]
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.[40]
Main article:
Agent OrangeAgent Orange was the code name for one of the herbicides and defoliants used by the U.S. military as part of its herbicidal warfare program, Operation Ranch Hand, during the Vietnam War from 1961 to 1971.
A 50:50 mixture of 2,4,5-T and 2,4-D, it was manufactured for the U.S. Department of Defense primarily by Monsanto Corporation and Dow Chemical. The 2,4,5-T used to produce Agent Orange was later discovered to be contaminated with 2,3,7,8-Tetrachlorodibenzodioxin, an extremely toxic dioxin compound. It was given its name from the color of the orange-striped 55 US gallon (200 L) barrels in which it was shipped, and was by far the most widely used of the so-called "Rainbow Herbicides".[54]
During the Vietnam war, between 1962 and 1971, the United States military sprayed 20,000,000 US gallons (76,000,000 L) of chemical herbicides and defoliants in Vietnam, eastern Laos and parts of Cambodia, as part of Operation Ranch Hand.[55] The program's goal was to defoliate forested and rural land, depriving guerrillas of cover; another goal was to induce forced draft urbanization, destroying the ability of peasants to support themselves in the countryside, and forcing them to flee to the U.S. dominated cities, thus depriving the guerrillas of their rural support base and food supply.[56][57]
Air Force records show that at least 6,542 spraying missions took place over the course of Operation Ranch Hand.[58] 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.[59] In South Vietnam alone, an estimated 10 million hectares of agricultural land were ultimately destroyed.[60] 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.[61][62] Overall, more than 20% of South Vietnam's forests were sprayed at least once over a nine-year period.[57]
The US began to target food crops in October 1962, primarily using Agent Blue. In 1965, 42% of all herbicide spraying was dedicated to food crops.[57] Rural-to-urban migration rates dramatically increased in South Vietnam, as peasants escaped the destruction and famine in the countryside by fleeing to the U.S.-dominated cities. The urban population in South Vietnam more than tripled: from 2.8 million people in 1958, to 8 million by 1971. The rapid flow of people led to a fast-paced and uncontrolled urbanization; an estimated 1.5 million people were living in Saigon slums, while many South Vietnamese elites and U.S. personnel lived in luxury.[63]
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.[64]
- In 1963, a dioxin cloud escapes after an explosion in a Philips-Duphar plant (now Solvay Group) near Amsterdam.[2] The plant was so polluted with dioxin after the accident that it had to be dismantled, embedded in concrete, and dumped into the ocean.[66][67][68]
Spolana Neratovice chloralkali plant, air view
- Between 1965 and 1968 production of 2,4,5-trichlorophenol in Spolana Neratovice plant in Czechoslovakia seriously poisoned about 60 workers with dioxins; after 3 years of investigations of the health problems of workers, Spolana stopped manufacture of 2,4,5-T (most of which was supplied to the US military in Vietnam). Several buildings of the Spolana chemical plant were heavily contaminated by dioxins.[69] Unknown amounts of dioxins were flushed into the Elbe and Mulde rivers during the 2002 European flood, contaminating the soils.[70] Analysis of eggs and ducks found levels of dioxins 15-time higher than EU limit and high concentrations of dioxin-like PCBs in the village of Libiš.[71] In 2004, the state health authority published a study which analysed the level of toxic substances in human blood near Spolana. According to the study, blood dioxin levels in Neratovice, Libiš and Tišice were about twice the level of the control group in Benešov. The quantity of dioxin chemicals near Spolana is significantly higher than the background level in other countries, e.g., USA, Japan or Spain. According to the US EPA, even the background level can pose a risk of cancer from 1:10000 up to 1:1000, about 100 times higher than normal.[72] The consumption of local fish, eggs, poultry and some produce was prohibited because of the post-flood contamination.[73]
- Also during 1965 through 1968, Dr. Albert M. Kligman was contracted by the Dow Chemical Company to perform threshold tests for TCDD on inmates at Holmesburg Prison in Philadelphia after Dow studies revealed adverse effects on workers at Dow's Midland, Michigan plant were likely due to TCDD. A subsequent test by Dow in rabbit ear models when exposed to 4–8 ug usually caused a severe response. The human studies carried out in Holmesburg failed to follow Dow's original protocol and lacked proper informed consent by the participants. As a result of poor study design and subsequent destruction of records, the tests were virtually worthless even though ten inmates were exposed to 7,500 ug of TCDD.[74]
- In 1976, large amounts of dioxins were released in an industrial accident at Seveso, although no immediate human fatalities or birth defects occurred.[75][76][77]
- Explosions resulting from the terrorist attacks on the US on September 11, 2001, released massive amounts of dust into the air. The air was measured for dioxins from September 23, 2001, to November 21, 2001, and reported to be "likely the highest ambient concentration that have ever been reported [in history]." The United States Environmental Protection Agency report dated October 2002 and released in December 2002 titled "Exposure and Human Health Evaluation of Airborne Pollution from the World Trade Center Disaster" authored by the EPA Office of Research and Development in Washington states that dioxin levels recorded at a monitoring station on Park Row near City Hall Park in New York between October 12 and 29, 2001, averaged 5.6 parts per trillion, or nearly six times the highest dioxin level ever recorded in the U.S. Dioxin levels in the rubble of the World Trade Centers were much higher with concentrations ranging from 10 to 170 parts per trillion. The report did no measuring of the toxicity of indoor air.
- In a 2001 case study,[30] physicians reported clinical changes in a 30-year-old woman who had been exposed to a massive dosage (144,000 pg/g blood fat) of dioxin equal to 16,000 times the normal body level; the highest dose of dioxin ever recorded in a human. She suffered from chloracne, nausea, vomiting, epigastric pain, loss of appetite, leukocytosis, anemia, amenorrhoea and thrombocytopenia. However, other notable laboratory tests, such as immune function tests, were relatively normal. The same study also covered a second subject who had received a dosage equivalent to 2,900 times the normal level, who apparently suffered no notable negative effects other than chloracne. These patients were provided with olestra to accelerate dioxin elimination.[81]
- In 2004, in a notable individual case of dioxin poisoning, Ukrainian politician Viktor Yushchenko was exposed to the second-largest measured dose of dioxins, according to the reports of the physicians responsible for diagnosing him. This is the first known case of a single high dose of TCDD dioxin poisoning, and was diagnosed only after a toxicologist recognized the symptoms of chloracne while viewing television news coverage of his condition.[11]
- In the early 2000s, residents of the city of New Plymouth, New Zealand, reported many illnesses of people living around and working at the Dow Chemical plant. This plant ceased production of 2,4,5-T in 1987.
- DuPont has been sued by 1,995 people who claim dioxin emissions from DuPont's plant in DeLisle, Mississippi, caused their cancers, illnesses or loved ones' deaths; of these only 850 were pending as of June 2008. In August 2005, Glen Strong, an oyster fisherman with the rare blood cancer multiple myeloma, was awarded $14 million from DuPont, but the ruling was overturned June 5, 2008, by a Mississippi jury who found DuPont's plant had no connection to Mr. Strong's disease.[82] In another case, parents claimed dioxin from pollution caused the death of their 8-year-old daughter; the trial took place in the summer of 2007, and a jury wholly rejected the family's claims, as no scientific connection could be proven between DuPont and the family's tragic loss.[83] DuPont's DeLisle plant is one of three titanium dioxide facilities (including Edgemoor, Delaware, and New Johnsonville, Tennessee) that are the largest producers of dioxin in the country, according to the US EPA's Toxic Release Inventory. DuPont maintains its operations are safe and environmentally responsible.
- In 2007 in Italy thousands of tonnes of foul-smelling refuse were piled up in Naples and its surrounding villages, defacing entire neighbourhoods. Polychlorinated dibenzodioxins were found in animals and humans over the lethal dose.[84] Sources of polychlorinated dibenzodioxins were identified in refuse and PVC combustion and industrial refuse disposal in uncontrolled industrial waste disposal. Lethal doses were found in numbers of animals and humans.
- In December 2008 in Ireland dioxin levels in pork were disclosed to have been between 80 and 200 times the legal limit. All Irish pork products were withdrawn from sale both nationally and internationally.
In this case the dioxin toxicity was found to be mostly due to dioxin-like polychlorinated dibenzofurans and polychlorinated biphenyls, and the contribution from actual polychlorinated dibenzodioxins was relatively low. It is thought that the incident resulted from the contamination of fuel oil used in a drying burner at a single feed processor, with PCBs. The resulting combustion produced a highly toxic mixture of PCBs, dioxins and furans, which was included in the feed produced and subsequently fed to a large number of pigs.[85]
- According to the last available data,[86] in 2005 the production of dioxin by the steel industry ILVA in Taranto (Italy) accounted for 90.3 per cent of the overall Italian emissions, and 8.8 per cent of the European emissions.
- German dioxin incidence: In January 2011 about 4700 German farms were banned from making deliveries after self-checking of an animal feed producer had showed levels of dioxin above maximum levels. This incident appeared to involve PCDDs and not PCBs.[13] Dioxins were found in animal feed and eggs in many farms. The maximum values were exceeded twofold in feed and maximally fourfold in some individual eggs.[13] Thus the incident was minor as compared with the Belgian crisis in 1999, and delivery bans were rapidly cleared.[87]
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.[88]
- Dioxins and dioxin-like compounds
- Agent Orange – one of the widest dioxin exposure incidents, where U.S. military planes released a dioxin-contaminated herbicide over large areas of Vietnam.
- Polychlorinated dibenzofurans (PCDFs) – A group of compounds, produced by the same conditions as dioxins and commonly co-present with dioxins in contamination incidents. They have the same toxic mode of action and are included in the toxic equivalent scheme for the purposes of assessing dioxin levels.
- Chemetco – this former copper smelter is cited in an academic study as one of the 10 highest ranking sources of dioxin pollution reaching Nunavut in the Canadian Arctic
- Polychlorinated biphenyls – A group of compounds historically used in the manufacture of electrical transformers certain members of which can also contribute to dioxin-like toxicity. These dioxin like compounds are also included in the toxic equivalent scheme when measuring dioxin levels.
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