Polychlorinated dibenzodioxins


Polychlorinated dibenzodioxins, 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, in the chlorine bleaching of paper, and from natural sources such as volcanoes and forest fires. 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.
The word "dioxins" may also refer to other similarly acting chlorinated compounds.

Chemical structure of dibenzo-1,4-dioxins

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.
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 scheme.

Historical perspective

Low concentrations of dioxins existed in nature prior to industrialization as a result of natural combustion and geological processes. Dioxins were first unintentionally produced as by-products from 1848 onwards as Leblanc process plants started operating in Germany. 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, became well known as a contaminant of Agent Orange, a herbicide used in the Malayan Emergency and the Vietnam War. Later, dioxins were found in Times Beach, Missouri and Love Canal, New York and Seveso, Italy. More recently, dioxins have been in the news with the poisoning of President Viktor Yushchenko of Ukraine in 2004, the Naples Mozzarella Crisis the 2008 Irish pork crisis, and the German feed incident of 2010.

Metabolism

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 in humans ranges from 4.9 to 13.1 years.
The persistence of a particular dioxin congener in an animal is thought to be a consequence of its structure. Dioxins with no lateral chlorines, which thus contain hydrogen atoms on adjacent pairs of carbons, can more readily be oxidized by cytochromes P450. The oxidized dioxins can then be more readily excreted rather than stored for a long time.

Toxicity

is considered the most toxic of the congeners. Other dioxin congeners including PCDFs and PCBs with dioxin-like toxicity, are given a toxicity rating from 0 to 1, where TCDD = 1. 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. 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 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.
Dioxins and other persistent organic pollutants 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

Dioxins build up primarily in fatty tissues over time, 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 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. TCDD has a half-life of approximately 8 years in humans, although at high concentrations, the elimination rate is enhanced by metabolism. The health effects of dioxins are mediated by their action on a cellular receptor, the aryl hydrocarbon receptor.
Exposure to high levels of dioxins in humans causes a severe form of persistent acne, known as chloracne. 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. Other effects in humans 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.
Dioxins accumulate in food chains in a fashion similar to other chlorinated compounds. 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. 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. 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:
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.

Agent Orange

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, an extremely toxic dioxin compound.
During the Vietnam war, between 1962 and 1971, the United States military sprayed of chemical herbicides and defoliants in Vietnam, eastern Laos and parts of Cambodia, as part of Operation Ranch Hand.
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. In South Vietnam alone, an estimated 10 million hectares of agricultural land were ultimately destroyed. 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.
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. The Red Cross of Vietnam estimates that up to 1 million people are disabled or have health problems due to Agent Orange contamination. The United States government has challenged these figures as being unreliable and unrealistically high.

Dioxin exposure incidents

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. Concentrations are determined by measuring the ratio of the analyte to the appropriate isotopically labeled internal standard.
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.