Dioxins and dioxin-like compounds (DLCs) are a group of
chemical compound
A chemical compound is a chemical substance composed of many identical molecules (or molecular entities) containing atoms from more than one chemical element held together by chemical bonds. A molecule consisting of atoms of only one element ...
s that are
persistent organic pollutant
Persistent organic pollutants (POPs), sometimes known as "forever chemicals", are organic compounds that are resistant to environmental degradation through chemical, biological, and photolytic processes. They are toxic chemicals that adversely ...
s (POPs) in the
environment
Environment most often refers to:
__NOTOC__
* Natural environment, all living and non-living things occurring naturally
* Biophysical environment, the physical and biological factors along with their chemical interactions that affect an organism or ...
. They are mostly
by-product
A by-product or byproduct is a secondary product derived from a production process, manufacturing process or chemical reaction; it is not the primary product or service being produced.
A by-product can be useful and marketable or it can be consid ...
s of burning or various industrial processes - or, in case of dioxin-like
PCBs
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 t ...
and
PBBs, unwanted minor components of intentionally produced mixtures.
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 the
aryl hydrocarbon receptor
The aryl hydrocarbon receptor (also known as AhR, AHR, ahr, ahR, or dioxin receptor) is a protein that in humans is encoded by the AHR gene. The aryl hydrocarbon receptor is a transcription factor that regulates gene expression. It was originall ...
(AH receptor), albeit with very different binding affinities, leading to high differences in toxicity and other effects. They include:
[Synopsis on dioxins and PCBs]
/ref>[
* Polychlorinated dibenzo''-p-''dioxins (PCDDs), or simply dioxins. PCDDs are derivatives of dibenzo''-p-''dioxin. There are 75 PCDD congeners, differing in the number and location of chlorine atoms, and 7 of them are specifically toxic, the most toxic being ]2,3,7,8-tetrachlorodibenzodioxin
2,3,7,8-Tetrachlorodibenzo-''p-''dioxin (TCDD) is a polychlorinated dibenzo''-p-''dioxin (sometimes shortened, though inaccurately, to simply 'dioxin')Tuomisto, Jouko (2019) Dioxins and dioxin-like compounds: toxicity in humans and animals, s ...
(TCDD).
* Polychlorinated dibenzofurans
More thorough treatise of all groups with similar actions and binding to aryl hydrocarbon receptor is given in Dioxins and dioxin-like compounds.
Polychlorinated dibenzofurans (PCDFs) are a family of organic compounds with one or several of the ...
(PCDFs), or furan
Furan is a heterocyclic organic compound, consisting of a five-membered aromatic ring with four carbon atoms and one oxygen atom. Chemical compounds containing such rings are also referred to as furans.
Furan is a colorless, flammable, highly ...
s. PCDFs are derivatives of dibenzofuran
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 t ...
. There are 135 isomers; 10 have dioxin-like properties.
* Polychlorinated biphenyl
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 t ...
s (PCBs), derived from biphenyl
Biphenyl (also known as diphenyl, phenylbenzene, 1,1′-biphenyl, lemonene or BP) is an organic compound that forms colorless crystals. Particularly in older literature, compounds containing the functional group consisting of biphenyl less one ...
, of which 12 are "dioxin-like". Under certain conditions PCBs may form dibenzofurans through partial oxidation.
* Polybrominated analogs of the above classes may have similar effects.
* "Dioxin" can also refer to 1,4-dioxin
1,4-Dioxin (also referred as dioxin or ''p''-dioxin) is a heterocyclic, organic, non-aromatic compound with the chemical formula CHO. There is an isomeric form of 1,4-dioxin, 1,2-dioxin (or ''o''-dioxin). 1,2-Dioxin is very unstable due to its ...
or ''p-''dioxin, the basic chemical unit of the more complex dioxins. This simple compound is not persistent and has no PCDD-like toxicity.
File:PCDD general structure.png, Polychlorinated dibenzo''-p-''dioxins
File:PCDF general structure.svg, Polychlorinated dibenzofurans
More thorough treatise of all groups with similar actions and binding to aryl hydrocarbon receptor is given in Dioxins and dioxin-like compounds.
Polychlorinated dibenzofurans (PCDFs) are a family of organic compounds with one or several of the ...
File:PCB structure general.svg, Polychlorinated biphenyl
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 t ...
s
File:1,4-Dioxin.svg, 1,4-dioxin
1,4-Dioxin (also referred as dioxin or ''p''-dioxin) is a heterocyclic, organic, non-aromatic compound with the chemical formula CHO. There is an isomeric form of 1,4-dioxin, 1,2-dioxin (or ''o''-dioxin). 1,2-Dioxin is very unstable due to its ...
Dioxins have different toxicity depending on the number and position of the chlorine
Chlorine is a chemical element with the Symbol (chemistry), symbol Cl and atomic number 17. The second-lightest of the halogens, it appears between fluorine and bromine in the periodic table and its properties are mostly intermediate betwee ...
atoms. Because dioxins refer to such a broad class of compounds that vary widely in toxicity, the concept of toxic equivalency factor 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.Van den Berg M, Birnbaum LS, Denison M, De Vito M, Farland W, Feeley F, Fiedler H, Hakansson H, Hanberg A, Haw ...
(TEF) has been developed to facilitate risk assessment and regulatory control. TEFs exist for seven congeners of dioxins, ten furans and twelve PCBs. The reference congener is the most toxic dioxin TCDD which per definition has a TEF of one. In essence, multiplying the amount of a particular congener with its TEF produces the amount toxicologically equivalent to TCDD, and after this conversion all dioxin-like congeners can be summed up, and the resulting toxicity equivalent quantity (TEQ) gives an approximation of toxicity of the mixture measured as TCDD.
Dioxins are virtually insoluble in water but have a relatively high solubility in lipid
Lipids are a broad group of naturally-occurring molecules which includes fats, waxes, sterols, fat-soluble vitamins (such as vitamins A, D, E and K), monoglycerides, diglycerides, phospholipids, and others. The functions of lipids include ...
s. Therefore, they tend to associate with organic matter such as plankton, plant leaves, and animal fat. In addition, they tend to be adsorbed to inorganic particles, such as ash and soil.
Dioxins are extremely stable and consequently tend to accumulate in the food chain
A food chain is a linear network of links in a food web starting from producer organisms (such as grass or algae which produce their own food via photosynthesis) and ending at an apex predator species (like grizzly bears or killer whales), det ...
. They are eliminated very slowly in animals, e.g. TCDD has a half-life
Half-life (symbol ) is the time required for a quantity (of substance) to reduce to half of its initial value. The term is commonly used in nuclear physics to describe how quickly unstable atoms undergo radioactive decay or how long stable ato ...
of 7 to 9 years in humans. Incidents of contamination with PCBs are often reported as dioxin contamination incidents since these are of most public and regulatory concern.[
Dioxins are a group of chemically related compounds that are persistent environmental pollutants. Dioxins are found throughout the world in the environment, and they accumulate in the food chain, mainly in the fatty tissue of animals. Dioxins are highly toxic and can cause reproductive and developmental problems, damage the nervous and immune systems, interfere with hormones, and also cause cancer. Owing to the highly toxic potential of dioxins, efforts need to be undertaken to reduce current background exposure. In these regards, prevention or reduction of human exposure and a strict control of industrial processes to reduce formation of dioxins are warranted.
]
Chemistry
There are 75 possible congeners of polychlorinated dibenzo''-p-''dioxins, but only 7 of them have affinity for the AH receptor and are toxic via this mechanism. The crucial structures are so called lateral chlorines in positions 2,3,7, and 8. These 4 chlorines also make the congeners persistent, because they prevent microbial degradation. Additional chlorines make the compounds less potent, but basically the effects remain the same although at higher doses. There are 135 possible dibenzofurans, and 10 in which the lateral chlorines are dioxin-like.[
There are 209 PCB compounds. Analogously to PCDDs at least two lateral chlorines in each ring in positions 3,4, and/or 5 are needed for dioxin-like activity. Because the AH receptor requires a planar (flat) structure, only PCB congeners that can rotate freely along the C—C axis between the rings can attach the receptor. Substituents in ortho-positions 2 and 6 prevent rotation and thus hinder the molecule from assuming a planar position. Mono-ortho congeners (one Cl in 2, 2', 6, or 6') have minimal activity. No significant dioxin-like activities have been noticed, if there are two or more o-chlorines.][ Brominated dioxins and biphenyls have similar properties, but they have been studied much less.][
]
Many natural compounds have very high affinity to AH receptors. These include indoles, flavones, benzoflavones, imidazoles and pyridines.[ These compounds are metabolized rapidly, but continuous intake from food may cause similar receptor activation as the background levels of dioxins. They do not reach concentrations causing typical dioxin-like toxicity, however.
]
Mechanism of action
The AH receptor is an ancient receptor, and its many functions have been revealed only recently.[Hahn, Mark E.; Karchner, Sibel I. (2011). "Structural and Functional Diversification of AHRs during Metazoan Evolution". The AH Receptor in Biology and Toxicology. John Wiley & Sons, Ltd. pp. 387–403. ] It is an over 600 million year old protein occurring in all vertebrates, and its homologs
A couple of homologous chromosomes, or homologs, are a set of one maternal and one paternal chromosome that pair up with each other inside a cell during fertilization. Homologs have the same genes in the same locus (genetics), loci where they pr ...
have been discovered in invertebrates and insects. It belongs to basic Helix–Loop–Helix
A basic helix–loop–helix (bHLH) is a protein structural motif that characterizes one of the largest families of dimerizing transcription factors. The word "basic" does not refer to complexity but to the chemistry of the motif because transc ...
-PAS proteins and acts as a transcription factor modifying transcription of a number of genes (see figure).[ AH receptor activity is necessary for normal development and many physiological functions. Mice lacking the AH receptor (knockouts) are sick with cardiac hypertrophy, liver fibrosis, reproductive problems, and impaired immunology.][
The AH receptor is relevant in toxicology for two very different reasons. First, it induces several enzymes important in the metabolism of foreign substances, so called ]xenobiotic
A xenobiotic is a chemical substance found within an organism that is not naturally produced or expected to be present within the organism. It can also cover substances that are present in much higher concentrations than are usual. Natural compo ...
s. These include both oxidative phase I enzymes and conjugative phase II enzymes, e.g. CYP1A2, CYP1B1, CYP2S1, CYP2A5, ALDH3, GSTA1, UGT1A1, UGT1A6, UGT1A7 and NQO1. This is in essence a protective function preventing toxic or carcinogenic effects of xenobiotics, but in some conditions it may also result in the production of reactive metabolites that are mutagenic and carcinogenic. This enzyme induction can be initiated by many natural or synthetic compounds, e.g., carcinogenic
A carcinogen is any substance, radionuclide, or radiation that promotes carcinogenesis (the formation of cancer). This may be due to the ability to damage the genome or to the disruption of cellular metabolic processes. Several radioactive substan ...
polycyclic hydrocarbons such as benzo''(a)''pyrene,[ several natural compounds,][ and dioxins.][ Secondly, AH receptors are involved in the activation or silencing of genes that lead to the toxic effects of high doses of dioxins.][ Because TCDD at high doses can influence the transcription of perhaps hundreds of genes, the genes crucial for the multitude of toxic effects of dioxins are still not known very well.]
Binding of dioxin-like compounds to the AH receptor has made it possible to measure total dioxin-like activity of a sample using CALUX (Chemical Activated LUciferase gene eXpression) bioassay. The results have been comparable to TEQ levels measured by much more expensive gas chromatography-high resolution mass spectrometry in environmental samples.
Toxicity
Dioxin toxicity is based on inappropriate activation of a physiologically important receptor, and therefore dose-response must be carefully considered.[ Inappropriate stimulation of many receptors leads to toxic outcomes, e.g. overdose of ]vitamin A
Vitamin A is a fat-soluble vitamin and an essential nutrient for humans. It is a group of organic compounds that includes retinol, retinal (also known as retinaldehyde), retinoic acid, and several provitamin A carotenoids (most notably bet ...
leads to inappropriate activation of retinoid receptor
Retinoid receptors are nuclear receptors (a class of protein
Proteins are large biomolecules and macromolecules that comprise one or more long chains of amino acid residues. Proteins perform a vast array of functions within organisms, incl ...
s resulting in e.g. malformations, and overdoses of corticosteroids
Corticosteroids are a class of steroid hormones that are produced in the adrenal cortex of vertebrates, as well as the synthetic analogues of these hormones. Two main classes of corticosteroids, glucocorticoids and mineralocorticoids, are involve ...
or sex hormones
Sex hormones, also known as sex steroids, gonadocorticoids and gonadal steroids, are steroid hormones that interact with vertebrate steroid hormone receptors. The sex hormones include the androgens, estrogens, and progestogens. Their effects are ...
lead to a multitude of adverse effects. Therefore it is important to separate the effects of low doses causing activation of the receptor around the physiological range from the effects of high toxic doses. This is all the more important because of large differences in exposures even among human beings. Western populations today are exposed to dioxins at doses leading to concentrations of 5 to 100 picograms/g (as TEQ in body fat), and the highest concentrations in accidental or deliberate poisonings have been 10,000 to 144,000 pg/g leading to dramatic but not lethal outcomes.[
The most relevant toxic outcomes of dioxins both in humans and animals are cancer and the developmental effects of offspring. Both have been documented at high doses, most accurately in animal experiments. As to developmental effects there is an agreement that the present dioxin levels in many populations are not very far from those causing some effects, but there is not yet consensus on the safe level.][ As to cancer, there is a disagreement on how to extrapolate the risk from high toxic doses to the present low exposures.][
While the affinity of dioxins and related industrial toxicants to the Ah receptor may not fully explain all their toxic effects including immunotoxicity, ]endocrine
The endocrine system is a messenger system comprising feedback loops of the hormones released by internal glands of an organism directly into the circulatory system, regulating distant target organs. In vertebrates, the hypothalamus is the neu ...
effects and tumor promotion Tumor promotion is a process in carcinogenesis by which various factors permit the descendants of a single initiated cell to survive and expand in number, i.e. to resist apoptosis and to undergo clonal growth. This is a step toward tumor progress ...
, toxic responses appear to be typically dose-dependent within certain concentration ranges. A multiphasic dose–response relationship
The dose–response relationship, or exposure–response relationship, describes the magnitude of the response of an organism, as a function of exposure (or doses) to a stimulus or stressor (usually a chemical) after a certain exposure time. ...
has also been reported, leading to uncertainty and debate about the true role of dioxins in cancer rates. The endocrine disrupting activity of dioxins is thought to occur as a down-stream function of AH receptor activation, with thyroid status in particular being a sensitive marker of exposure. TCDD, along with the other PCDDs, PCDFs and dioxin-like coplanar PCBs are not direct agonists or antagonists of hormones, and are not active in assays which directly screen for these activities such as ER-CALUX and AR-CALUX. These compounds have also not been shown to have any direct mutagenic
In genetics, a mutagen is a physical or chemical agent that permanently changes genetic material, usually DNA, in an organism and thus increases the frequency of mutations above the natural background level. As many mutations can cause cancer in ...
or genotoxic Genotoxicity is the property of chemical agents that damage the genetic information within a cell causing mutations, which may lead to cancer. While genotoxicity is often confused with Mutagen, mutagenicity, all mutagens are genotoxic, but some geno ...
activity. Their main action in causing cancer is cancer promotion. A mixture of PCBs such as Aroclor may contain PCB compounds which are known estrogen agonists but are not classified as dioxin-like in terms of toxicity. Mutagenic effects have been established for some lower chlorinated chemicals such as 3-chlorodibenzofuran, which is neither persistent nor an AH receptor agonist.
Toxicity in animals
High doses. The symptoms reported to be associated with dioxin toxicity in animal studies are incredibly wide-ranging, both in the scope of the biological systems affected and in the range of dosage needed to bring these about.[ Acute effects of single high dose dioxin exposure include reduced feed intake and ]wasting syndrome
Cachexia () is a complex syndrome associated with an underlying illness, causing ongoing muscle loss that is not entirely reversed with nutritional supplementation. A range of diseases can cause cachexia, most commonly cancer, congestive heart f ...
, and typically a delayed death of the animal in 1 to 6 weeks.[ By far most toxicity studies have been performed using 2,3,7,8-tetrachlorodibenzo-''p''-dioxin.
The of TCDD varies wildly between species and even strains of the same species, with the most notable disparity being between the seemingly similar species of ]hamster
Hamsters are rodents (order Rodentia) belonging to the subfamily Cricetinae, which contains 19 species classified in seven genera.Fox, Sue. 2006. ''Hamsters''. T.F.H. Publications Inc. They have become established as popular small pets. The b ...
and guinea pig
The guinea pig or domestic guinea pig (''Cavia porcellus''), also known as the cavy or domestic cavy (), is a species of rodent belonging to the genus ''Cavia'' in the family Caviidae. Breeders tend to use the word ''cavy'' to describe the ani ...
. The oral for guinea pigs is as low as 0.5 to 2 μg/kg body weight, whereas the oral for hamsters can be as high as 1 to 5 mg/kg body weight.[ Even between different mouse or rat strains there may be tenfold to thousandfold differences in acute toxicity. Many pathological findings are seen in the ]liver
The liver is a major Organ (anatomy), organ only found in vertebrates which performs many essential biological functions such as detoxification of the organism, and the Protein biosynthesis, synthesis of proteins and biochemicals necessary for ...
, thymus
The thymus is a specialized primary lymphoid organ of the immune system. Within the thymus, thymus cell lymphocytes or ''T cells'' mature. T cells are critical to the adaptive immune system, where the body adapts to specific foreign invaders. ...
, and other organs. Some effects such as thymic atrophy are common in many species, but e.g. liver toxicity is typical in rabbits.[
Low doses. Very few signs of toxicity are seen in adult animals after low doses, but developmental effects may occur at low dioxin levels, including ]foetal
A fetus or foetus (; plural fetuses, feti, foetuses, or foeti) is the unborn offspring that develops from an animal embryo. Following embryonic development the fetal stage of development takes place. In human prenatal development, fetal develo ...
, neonatal
An infant or baby is the very young offspring of human beings. ''Infant'' (from the Latin word ''infans'', meaning 'unable to speak' or 'speechless') is a formal or specialised synonym for the common term ''baby''. The terms may also be used to ...
, and possibly pubescent stages. Well established developmental effects are cleft palate
A cleft lip contains an opening in the upper lip that may extend into the nose. The opening may be on one side, both sides, or in the middle. A cleft palate occurs when the palate (the roof of the mouth) contains an opening into the nose. The te ...
, hydronephrosis
Hydronephrosis describes hydrostatic dilation of the renal pelvis and calyces as a result of obstruction to urine flow downstream. Alternatively, hydroureter describes the dilation of the ureter, and hydronephroureter describes the dilation of t ...
, disturbances in tooth development
Tooth development or odontogenesis is the complex process by which teeth form from embryonic cells, grow, and erupt into the mouth. For human teeth to have a healthy oral environment, all parts of the tooth must develop during appropriate stag ...
and sexual development
Puberty is the process of physical changes through which a child's body matures into an adult body capable of sexual reproduction. It is initiated by hormonal signals from the brain to the gonads: the ovaries in a girl, the testes in a boy. In ...
, and endocrine
The endocrine system is a messenger system comprising feedback loops of the hormones released by internal glands of an organism directly into the circulatory system, regulating distant target organs. In vertebrates, the hypothalamus is the neu ...
effects.[ Surprisingly, enzyme induction, several developmental effects and aversion to novel foods occur at similar dose levels in animals that respond differently to acute high-dose toxicity. Therefore it has been suggested that dioxin effects be divided to type I effects (enzyme induction etc.) and type II effects (lethality, liver damage, anorexia, and tumour promotion).][ The reason may be different requirements of the transactivation domain structure of the AH receptor for different genes. Some of these low-dose effects can in fact be interpreted as protective rather than toxic (enzyme induction, aversion to novel foods).][
]
Human toxicity
High doses. Toxicity of dioxins at high doses has been well documented after accidents, deliberate poisonings, food contamination episodes, and high industrial exposures.[ Three women in Vienna, Austria, were poisoned with large doses of TCDD in 1998. The highest concentration of TCDD in fat tissue was 144,000 pg/g, the highest ever reported in human beings. The main feature was ]chloracne
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 ...
, a serious skin disease. The victim survived, and other symptoms were modest after initial gastrointestinal
The gastrointestinal tract (GI tract, digestive tract, alimentary canal) is the tract or passageway of the digestive system that leads from the mouth to the anus. The GI tract contains all the major organs of the digestive system, in humans and ...
symptoms and amenorrhea
Amenorrhea is the absence of a menstrual period in a woman of reproductive age. Physiological states of amenorrhoea are seen, most commonly, during pregnancy and lactation (breastfeeding). Outside the reproductive years, there is absence of menses ...
. Another acute incident was the deliberate poisoning of Victor Yushchenko
Viktor Andriyovych Yushchenko ( uk, Віктор Андрійович Ющенко, ; born 23 February 1954) is a Ukrainian politician who was the third president of Ukraine from 23 January 2005 to 25 February 2010.
As an informal leader of th ...
, then presidential candidate of Ukraine, in 2004. TCDD concentration in fat was 108,000 pg/g. Also in this case the most prominent symptom was chloracne after initial stomach pain indicating hepatitis
Hepatitis is inflammation of the liver tissue. Some people or animals with hepatitis have no symptoms, whereas others develop yellow discoloration of the skin and whites of the eyes (jaundice), poor appetite, vomiting, tiredness, abdominal pa ...
and pancreatitis
Pancreatitis is a condition characterized by inflammation of the pancreas. The pancreas is a large organ behind the stomach that produces digestive enzymes and a number of hormones. There are two main types: acute pancreatitis, and chronic pancr ...
. These episodes show that a human being is not as sensitive as the most sensitive animals, since the doses must have been up to 25 μg/kg.
Two serious food contamination accidents were caused by PCB oils used in heat exchangers.[ The PCB oil leaked to rice bran oil consumed by thousands of people in Japan ( Yusho disease 1968) and Taiwan ( Yu-cheng disease 1979). The toxic effects have been attributed to dioxin-like PCBs and PCDFs. Their daily intake was up to 100,000 times higher than average intake presently.][ There were many skin problems, chloracne, swelling of eyelids, and hypersecretion of ]Meibomian gland
Meibomian glands (also called tarsal glands, palpebral glands, and tarsoconjunctival glands) are sebaceous glands along the rims of the eyelid inside the tarsal plate. They produce meibum, an oily substance that prevents evaporation of the eye' ...
s in the eyes. Babies born to Yusho and Yu-cheng mothers were smaller than normal, they had dark pigmentation and sometimes teeth at birth and tooth deformities. Foetal deaths and miscarriages were common.
Perhaps the best known dioxin accident occurred in Seveso, Italy, in 1976. A tank of chlorophenol
A chlorophenol is any organochloride of phenol that contains one or more covalently bonded chlorine atoms. There are five basic types of chlorophenols (mono- to pentachlorophenol) and 19 different chlorophenols in total when positional isomerism is ...
s released its contents to air including many kilograms of TCDD, and contaminated much of the city. The highest TCDD levels were found in children, up to 56,000 pg/g fat. Acute effects were limited to chloracne, although many animals such as rabbits died after eating contaminated grass. Dental aberrations were found after 25 years in persons exposed as children, and a slightly increased cancer risk was confirmed 35 years later.[
In line with animal studies, developmental effects may be much more important than effects in adults. These include disturbances of ]tooth
A tooth ( : teeth) is a hard, calcified structure found in the jaws (or mouths) of many vertebrates and used to break down food. Some animals, particularly carnivores and omnivores, also use teeth to help with capturing or wounding prey, tear ...
development, and of sexual development.
An example of the variation in responses is clearly seen in a study following the Seveso disaster
Seveso (; lmo, label= Lombard, Séves ) is a town and ''comune'' in the Province of Monza and Brianza, in the Region of Lombardy. The economy of the town has traditionally been based on the furniture industry.
Its name comes from the river of ...
indicating that sperm
Sperm is the male reproductive cell, or gamete, in anisogamous forms of sexual reproduction (forms in which there is a larger, female reproductive cell and a smaller, male one). Animals produce motile sperm with a tail known as a flagellum, whi ...
count and motility were affected in different ways in exposed males, depending on whether they were exposed before, during or after puberty.
In occupational settings many symptoms have been seen, but exposures have always been to a multitude of chemicals including chlorophenol
A chlorophenol is any organochloride of phenol that contains one or more covalently bonded chlorine atoms. There are five basic types of chlorophenols (mono- to pentachlorophenol) and 19 different chlorophenols in total when positional isomerism is ...
s, chlorophenoxy acid herbicides, and solvent
A solvent (s) (from the Latin '' solvō'', "loosen, untie, solve") is a substance that dissolves a solute, resulting in a solution. A solvent is usually a liquid but can also be a solid, a gas, or a supercritical fluid. Water is a solvent for ...
s. Therefore, definitive proof of dioxins as causative factors has been difficult to obtain. By far the best proven effect is chloracne. The suspected effects in adults are liver damage, and alterations in heme
Heme, or haem (pronounced / hi:m/ ), is a precursor to hemoglobin, which is necessary to bind oxygen in the bloodstream. Heme is biosynthesized in both the bone marrow and the liver.
In biochemical terms, heme is a coordination complex "consisti ...
metabolism, serum lipid
Lipids are a broad group of naturally-occurring molecules which includes fats, waxes, sterols, fat-soluble vitamins (such as vitamins A, D, E and K), monoglycerides, diglycerides, phospholipids, and others. The functions of lipids include ...
levels, thyroid
The thyroid, or thyroid gland, is an endocrine gland in vertebrates. In humans it is in the neck and consists of two connected lobes. The lower two thirds of the lobes are connected by a thin band of tissue called the thyroid isthmus. The thy ...
functions, as well as diabetes
Diabetes, also known as diabetes mellitus, is a group of metabolic disorders characterized by a high blood sugar level ( hyperglycemia) over a prolonged period of time. Symptoms often include frequent urination, increased thirst and increased ap ...
and immunological effects.[
Low exposures. Effects after low exposures such as from food have been difficult to prove. Levels of dioxins in contemporary population are 5 to 20 pg/g (TEQ in fat) and 50 to 100 pg in older people] or at least 1000 times lower than those in poisonings (see above). Tooth deformities have been considered plausible after long breast-feeding, when the dioxin concentrations were high in 1970s and 1980s. When the concentrations decreased during 1990s and 2000s, the effects were no longer seen.[ According to a study in Russia, sperm counts in 18-19 year old young men were lower when dioxin levels were higher at the age of 8 to 9 years.] This was in industrial environments causing relatively high exposures to boys as well as their mothers.[ The contamination panel of the ]European Food Safety Agency
The European Food Safety Authority (EFSA) is the agency of the European Union (EU) that provides independent scientific advice and communicates on existing and emerging risks associated with the food chain. EFSA was established in February 2002, ...
(EFSA) recommended decreasing tolerable weekly intake (TWI) levels based on the Russian children study. This recommendation can be challenged, because it does not properly consider competing risks following from lost benefits of important and healthy food items such as certain fish.[ TWI levels are not applied for breast feeding, because benefits of breast milk are judged to be far more important than the remote risks of dioxins.] A general conclusion may be that safety margins are not very great concerning developmental effects, but toxic effects are not likely at the present population levels of dioxins.
A number of cross-sectional studies
In medical research, social science, and biology, a cross-sectional study (also known as a cross-sectional analysis, transverse study, prevalence study) is a type of observational study that analyzes data from a population, or a representative su ...
have shown associations between type 2 diabetes
Type 2 diabetes, formerly known as adult-onset diabetes, is a form of diabetes mellitus that is characterized by high blood sugar, insulin resistance, and relative lack of insulin. Common symptoms include increased thirst, frequent urination, ...
and several POP compounds including dioxins. Such observational studies cannot prove causality, i.e. there may be an association which does not prove that one is the cause of the other. The main problem is that similar associations can be found with many quite different POPs, which have only long half-lives
Half-life (symbol ) is the time required for a quantity (of substance) to reduce to half of its initial value. The term is commonly used in nuclear physics to describe how quickly unstable atoms undergo radioactive decay or how long stable at ...
and tendency to accumulate in lipids in common. This suggests that they may all be related to diet and obesity which are by far the most common causes of type 2 diabetes.[
Over the years there have been speculations on various effects of dioxins on ]endometriosis
Endometriosis is a disease of the female reproductive system in which cells similar to those in the endometrium, the layer of tissue that normally covers the inside of the uterus, grow outside the uterus. Most often this is on the ovaries, f ...
, sexual development, liver function
Liver function tests (LFTs or LFs), also referred to as a hepatic panel, are groups of blood tests that provide information about the state of a patient's liver. These tests include prothrombin time (PT/INR), activated partial thromboplastin tim ...
, thyroid hormone
File:Thyroid_system.svg, upright=1.5, The thyroid system of the thyroid hormones T3 and T4
rect 376 268 820 433 Thyroid-stimulating hormone
rect 411 200 849 266 Thyrotropin-releasing hormone
rect 297 168 502 200 Hypothalamus
rect 66 216 386 25 ...
levels, white blood cell
White blood cells, also called leukocytes or leucocytes, are the cell (biology), cells of the immune system that are involved in protecting the body against both infectious disease and foreign invaders. All white blood cells are produced and de ...
levels, immune
In biology, immunity is the capability of multicellular organisms to resist harmful microorganisms. Immunity involves both specific and nonspecific components. The nonspecific components act as barriers or eliminators of a wide range of pathogens ...
functions, and even learning and intelligence. While some of these effects might be possible after heavy exposures (like in the Seveso disaster), these claims are only based on potential exposures of population, not supported by actual measurements of dioxin concentrations.[ E.g. absorption from bleached tampons claimed to be associated with endometriosis is insignificant compared with daily dioxin intake from food.][
]
Carcinogenicity
Dioxins are well established carcinogens
A carcinogen is any substance, radionuclide, or radiation that promotes carcinogenesis (the formation of cancer). This may be due to the ability to damage the genome or to the disruption of cellular metabolic processes. Several radioactive substan ...
in animal studies, although the precise mechanism is not clear. Dioxins are not mutagenic
In genetics, a mutagen is a physical or chemical agent that permanently changes genetic material, usually DNA, in an organism and thus increases the frequency of mutations above the natural background level. As many mutations can cause cancer in ...
or genotoxic Genotoxicity is the property of chemical agents that damage the genetic information within a cell causing mutations, which may lead to cancer. While genotoxicity is often confused with Mutagen, mutagenicity, all mutagens are genotoxic, but some geno ...
. The United States Environmental Protection Agency
The Environmental Protection Agency (EPA) is an independent executive agency of the United States federal government tasked with environmental protection matters. President Richard Nixon proposed the establishment of EPA on July 9, 1970; it be ...
has categorised dioxin, and the mixture of substances associated with sources of dioxin toxicity as a "likely human carcinogen". The International Agency for Research on Cancer
The International Agency for Research on Cancer (IARC; french: Centre International de Recherche sur le Cancer, CIRC) is an intergovernmental agency forming part of the World Health Organization of the United Nations.
Its role is to conduct and ...
has classified TCDD as a human carcinogen (class 1) on the basis of clear animal carcinogenicity and limited human data,[IARC Monographs on the Evaluation of Carcinogenic Risks to Humans, Volume 69, Lyon, 1997] and subsequently also 2,3,4,7,8-PCDF and PCB 126 as class 1 carcinogens. The mechanism is thought to be mainly promotion, i.e. dioxins can accelerate the formation of tumours caused by other factors, and adversely affect the normal mechanisms for inhibiting tumour growth.[ Some researchers have also proposed that dioxin induces cancer progression through a very different mitochondrial pathway.
As with many toxic endpoints of dioxin, a clear dose–response relationship is difficult to establish. After accidental or high occupational exposures there is evidence on human carcinogenicity.] Increases in cancer have been modest, in fact reaching statistical significance has been difficult even after high accidental or occupational exposures like in Yusho and Yucheng poisonings, Seveso accident, and combined occupational cohorts.[ Therefore controversies on cancer risk at low population levels of dioxins are understandable.][ The problem with IARC evaluations] is that they only assess hazard, i.e. carcinogenicity at any dose. It is likely that there is a practical safe threshold for the non-genotoxic dioxins, and the present population levels do not possess any risk of cancer. There is thus some agreement on that cancer risk is taken care of as well, if daily intake limits are set to protect from developmental effects.[ Among fishermen with high dioxin concentrations in their bodies, cancer deaths were decreased rather than increased.] All this means that in case of important beneficial food items and breast feeding a thorough benefit/risk analysis is needed before setting limits, in order to avoid increased other risks or lost benefits.
Risk assessment
The uncertainty and variability in the dose–response relationship of dioxins in terms of their toxicity, as well as the ability of dioxins to bioaccumulate
Bioaccumulation is the gradual accumulation of substances, such as pesticides or other chemicals, in an organism. Bioaccumulation occurs when an organism absorbs a substance at a rate faster than that at which the substance is lost or eliminated ...
, have led WHO experts to recommending very low tolerable daily intake Tolerable daily intake (TDI) refers to the daily amount of a chemical that has been assessed safe for human being on long-term basis (usually whole lifetime). Originally acceptable daily intake (ADI) was introduced in 1961 to define the daily intake ...
(TDI) of dioxin, 1-4 pg/kg body weight per day, i.e. 7x10−11 to 2.8x10−10g per 70-kg person per day, to allow for this uncertainty and ensure public safety in all instances.[ Authorities have then set weekly or monthly intake levels that equal to TDIs around 2 pg/kg.][ Because dioxins are eliminated very slowly, the ]body burden
In analytical chemistry, biomonitoring is the measurement of the body burden of toxic chemical compounds, elements, or their metabolites, in biological substances. Often, these measurements are done in blood and urine. Biomonitoring is performe ...
accumulated during the whole lifetime is high compared with daily doses, and occasional modest exceedances of limit values do not change it much. Therefore long-term intake is much more important than daily intake.[ Specifically, the TDI has been assessed to guarantee the safety of children born to mothers exposed to such a daily intake of dioxins all their lifetime prior to pregnancy.][ It is likely that the TDI for other population groups could be higher.
One important cause for differences in different assessments has been carcinogenicity. If the dose-response of TCDD in causing cancer is linear, it might be a true risk. If the dose-response is of a threshold-type or J-shape, there is little or no risk at the present concentrations. Understanding the mechanisms of toxicity better is hoped to increase the reliability of risk assessment.][ Recently also developmental effects have been reassessed by the Contamination Panel of the ]European Food Safety Agency
The European Food Safety Authority (EFSA) is the agency of the European Union (EU) that provides independent scientific advice and communicates on existing and emerging risks associated with the food chain. EFSA was established in February 2002, ...
(EFSA). They propose decreasing the tolerable weekly intake (TWI) from 14 pg/kg to 2 pg/kg.[ This is likely to cause another controversy before being accepted by European countries.][ Dioxin intake and levels in breast milk in 1970s and 1980s were 5 to 10 times higher than presently, and very few effects have been found, possibly mild developmental effects on teeth.][
]
Controversy
Greenpeace
Greenpeace is an independent global campaigning network, founded in Canada in 1971 by Irving Stowe and Dorothy Stowe, immigrant environmental activists from the United States. Greenpeace states its goal is to "ensure the ability of the Earth t ...
and some other environmental groups have called for the chlorine industry to be phased out.[Sharon Beder]
'The dioxin controversy: spilling over into schools'
''Australian Science Teachers' Journal'', November 1998, pp. 28-34.[ However, chlorine industry supporters say that "banning chlorine would mean that millions of people in the third world would die from want of disinfected water". ]Sharon Beder
Sharon Beder is an environmentalist and a former professor in the Faculty of Arts at the University of Wollongong in New South Wales, Australia. and others have argued that the dioxin controversy has been very political and that large companies have tried to play down the seriousness of the problems of dioxin.[Sharon Beder (2000). ''Global Spin: The Corporate Assault on Environmentalism'', Scribe Publications, chapters 9 and 13.] The companies involved have often said that the campaign against dioxin is based on "fear and emotion" and not on science.
Human intake and levels
Most intake of dioxin-like chemicals is from food of animal origin: meat, dairy products, or fish predominate, depending on the country.[ The daily intake of dioxins and dioxin-like PCBs as TEQ is of the order of 100 pg/day, i.e. 1-2 pg/kg/day.][ In many countries both the absolute and relative significance of dairy products and meat have decreased due to strict emission controls, and brought about the decrease of total intake. E.g. in the United Kingdom the total intake of PCDD/F in 1982 was 239 pg/day and in 2001 only 21 pg/day (WHO-TEQ).][ Since the half-lives are very long (for e.g. TCDD 7–8 years), the body burden will increase almost over the whole lifetime. Therefore, the concentrations may increase five to tenfold from age 20 to age 60.] For the same reason, short term higher intake such as after food contamination incidents, is not crucial unless it is extremely high or lasts for several months or years.[
]
The highest body burdens were found in Western Europe in the 1970s and early 1980s, and the trends have been similar in the U.S. The most useful measure of time trends is concentration in breast milk measured over decades.[ In many countries the concentrations have decreased to about one tenth of those in the 1970s, and the total TEQ concentrations are now of the order of 5-30 pg/g fat][ (please note the units, pg/g is the same as ng/kg, or the non-standard expression ppt used sometimes in the United States).][ The decrease is due to strict emission controls and also to the control of concentrations in food.] In the U.S. young adult female population (age group 20-39), the concentration was 9.7 pg/g lipid in 2001-2002 (geometric mean).
Certain professions such as subsistence fishermen
Artisanal fishing (or traditional/subsistence fishing) consists of various small-scale, low-technology, low-capital, fishing practices undertaken by individual fisherman, fishing households (as opposed to commercial fishing). Many of these househ ...
in some areas are exposed to exceptionally high amounts of dioxins and related substances. This along with high industrial exposures may be the most valuable source of information on the health risks of dioxins.[
]
Fate of dioxins in human body
Dioxins are absorbed well from the digestive tract if they are dissolved in fats or oils (e.g. in fish or meat).[ On the other hand, dioxins tend to adsorb tightly to soil particles, and absorption may be quite low: 13.8% of the given dose of TEQs in contaminated soil was absorbed.]
The same features causing persistence of dioxins in the environment also cause very slow elimination in humans and animals. Because of low water solubility, kidneys cannot excrete them in urine as such. They must first be metabolised to more-water-soluble metabolites, but that metabolism, especially in humans, is extremely slow. This results in biological half-lives
Half-life (symbol ) is the time required for a quantity (of substance) to reduce to half of its initial value. The term is commonly used in nuclear physics to describe how quickly unstable atoms undergo radioactive decay or how long stable at ...
of several years for all dioxins. That of TCDD is estimated to be 7 to 8 years, and for other PCDD/Fs from 1.4 to 13 years, PCDFs on average slightly shorter than PCDDs.[
In mammals, dioxins are found mostly in fat. Concentrations in fat seem to be relatively similar, be it serum fat, adipose tissue fat, or milk fat. This permits measuring dioxin burden by analysing breast milk.][ Initially, however, at least in laboratory animals, after a single dose, high concentrations are found in the liver, but in a few days, adipose tissue will predominate. In rat liver, however, high doses cause induction of CYP1A2 enzyme, and this binds dioxins. Thus, depending on the dose, the ratio of fat and liver tissue concentrations may vary considerably in rodents.][
]
Uses
Dioxins have no common uses. They are manufactured on a small scale for chemical and toxicological research, but mostly exist as by-product
A by-product or byproduct is a secondary product derived from a production process, manufacturing process or chemical reaction; it is not the primary product or service being produced.
A by-product can be useful and marketable or it can be consid ...
s of industrial processes such as chlorine bleaching of paper pulp
Pulp is a lignocellulosic fibrous material prepared by chemically or mechanically separating cellulose fibers from wood, fiber crops, waste paper, or rags. Mixed with water and other chemical or plant-based additives, pulp is the major raw mate ...
, pesticide
Pesticides are substances that are meant to control pests. This includes herbicide, insecticide, nematicide, molluscicide, piscicide, avicide, rodenticide, bactericide, insect repellent, animal repellent, microbicide, fungicide, and lampri ...
manufacture, and combustion processes such as incineration
Incineration is a waste treatment process that involves the combustion of substances contained in waste materials. Industrial plants for waste incineration are commonly referred to as waste-to-energy facilities. Incineration and other high ...
. The defoliant Agent Orange
Agent Orange is a chemical herbicide and defoliant, one of the "tactical use" Rainbow Herbicides. It was used by the U.S. military as part of its herbicidal warfare program, Operation Ranch Hand, during the Vietnam War from 1961 to 1971. It ...
contained dioxins. The wood preservative pentachlorophenol contained dioxins and dibenzofurans. The Stockholm Convention
Stockholm Convention on Persistent Organic Pollutants is an international environmental treaty, signed on 22 May 2001 in Stockholm and effective from 17 May 2004, that aims to eliminate or restrict the production and use of persistent organic ...
banned the production and use of dioxins in 2001.
Sources
Environmental sources
PCDD/F-compounds were never synthesized for any purpose, except for small quantities for scientific research.[ Small amounts of PCDD/Fs are formed whenever organics, oxygen and chlorine are available at suitable temperatures.][ This is augmented by metal catalysts such as copper. The optimal temperature range is to . This means that formation is highest when organic material is burned in less-than-optimal conditions such as open fires, building fires, domestic fireplaces, and poorly operated and/or designed solid waste incinerators.][ Historically, municipal and medical waste incineration was the most important source of PCDD/Fs.
PCB-compounds, always containing low concentrations of dioxin-like PCBs and PCDFs, were synthesized for various technical purposes (see ]Polychlorinated biphenyls
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 of 1976, Toxic Substances Contro ...
). They have entered the environment through accidents such as fires or leaks from transformers or heat exchangers, or from PCB-containing products in landfills or during incineration. Because PCBs are somewhat volatile, they have also been transported long distances by air leading to global distribution including the Arctic. Only a minor portion of PCBs in mixtures are dioxin-like.[
Other sources of PCDD/F include:
* Uncontrolled combustion, particularly open burning of waste ("backyard barrel burning"), accidental fires, wildfires. These are presently the most important sources.][
* Metal smelting and refining
* Chlorine bleaching of pulp and paper - historically important source of PCDD/Fs to waterways.]
* Synthesis side products of several chemicals, especially PCBs, chlorophenols, chlorophenoxy acid herbicides, and hexachlorophene
Hexachlorophene, also known as Nabac, is an organochlorine compound that was once widely used as a disinfectant. The compound occurs as a white odorless solid, although commercial samples can be off-white and possess a slightly phenolic odor. It ...
.[
* (Historical) Engines using ]leaded fuel
Tetraethyllead (commonly styled tetraethyl lead), abbreviated TEL, is an organolead compound with the formula Pb( C2H5)4. It is a fuel additive, first being mixed with gasoline beginning in the 1920s as a patented octane rating booster that al ...
, which contained the additives 1,2-Dichloroethane
The chemical compound 1,2-dichloroethane, commonly known as ethylene dichloride (EDC), is a chlorinated hydrocarbon. It is a colourless liquid with a chloroform-like odour. The most common use of 1,2-dichloroethane is in the production of vinyl ...
and 1,2-Dibromoethane
1,2-Dibromoethane, also known as ethylene dibromide (EDB), is an organobromine compound with the chemical formula . Although trace amounts occur naturally in the ocean, where it is formed probably by algae and kelp, it is mainly synthetic. It is a ...
.
In waste incineration
Improvements and changes have been made to nearly all industrial sources to reduce PCDD/F production. In waste incineration, large amounts of publicity and concern surrounded dioxin-like compounds during the 1980s-1990s continues to pervade the public consciousness, especially when new incineration and waste-to-energy
Waste-to-energy (WtE) or energy-from-waste (EfW) is the process of generating energy in the form of electricity and/or heat from the primary treatment of waste, or the processing of waste into a fuel source. WtE is a form of energy recovery. Mo ...
facilities are proposed. As a result of these concerns, incineration processes have been improved with increased combustion temperatures (over ), better furnace control, and sufficient residence time allotted to ensure complete oxidation of organic compounds. Ideally, an incineration process oxidizes all carbon to CO2 and converts all chlorine to HCl HCL may refer to:
Science and medicine
* Hairy cell leukemia, an uncommon and slowly progressing B cell leukemia
* Harvard Cyclotron Laboratory, from 1961 to 2002, a proton accelerator used for research and development
* Hollow-cathode lamp, a spe ...
or inorganic chlorides prior to the gases passing through the temperature window of 400-700 °C where PCDD/F formation is possible. These substances cannot easily form organic compounds, and HCl is easily and safely neutralized in the scrubber
Scrubber systems (e.g. chemical scrubbers, gas scrubbers) are a diverse group of air pollution control devices that can be used to remove some particulates and/or gases from industrial exhaust streams. An early application of a carbon dioxide scr ...
while CO2 is vented to the atmosphere. Inorganic chlorides are incorporated into the ash.
Scrubber and particulate removal systems manage to capture some of the PCDD/F which forms even in sophisticated incineration plants. These PCDD/Fs are generally not destroyed but moved into the fly ash
Fly ash, flue ash, coal ash, or pulverised fuel ash (in the UK) plurale tantum: coal combustion residuals (CCRs)is a coal combustion product that is composed of the particulates (fine particles of burned fuel) that are driven out of coal-fired ...
. Catalytic
Catalysis () is the process of increasing the rate of a chemical reaction by adding a substance known as a catalyst (). Catalysts are not consumed in the reaction and remain unchanged after it. If the reaction is rapid and the catalyst recyc ...
systems have been designed which destroy vapor-phase PCDD/Fs at relatively low temperatures. This technology is often combined with the baghouse
A baghouse, also known as a baghouse filter, bag filter, or fabric filter is an air pollution control device and dust collector that removes particulates or gas released from commercial processes out of the air. Power plants, steel mills, pharmaceu ...
or SCR system at the tail end of an incineration plant.
European Union limits for concentration of dioxin-like compounds in the discharged flue gas is 0.1 ng/Nm³ TEQ.
Both in Europe and in U.S.A., the emissions have decreased dramatically since the 1980s, by even 90% (see Figure). This has also led to decreases in human body burdens, which is neatly demonstrated by the decrease of dioxin concentrations in breast milk
Breast milk (sometimes spelled as breastmilk) or mother's milk is milk produced by mammary glands located in the breast of a human female. Breast milk is the primary source of nutrition for newborns, containing fat, protein, carbohydrates ( lacto ...
.[ With the substantial decrease of emissions from municipal waste incinerators, other potentially large sources of dioxin-like compounds, for example from forest and wild fires, have increased relative to industrial sources. They are however not included in the total inventory due to uncertainties in available data. A more recent study on the environmental effects of accidental fires, including ]forest fire
A wildfire, forest fire, bushfire, wildland fire or rural fire is an unplanned, uncontrolled and unpredictable fire in an area of Combustibility and flammability, combustible vegetation. Depending on the type of vegetation present, a wildfire ...
s, estimated the emissions from dioxins (PCDD/Fs) to be about equivalent to those from traffic and municipal waste combustion.
Open burning of waste (backyard barrel burning) has not decreased effectively, and in the U.S. it is now the most important source of dioxins. Total U.S. annual emissions decreased from in 1987 to in 2000. However, backyard barrel burning decreased only modestly from to , resulting in over one third of all dioxins in the year 2000 from backyard burning alone.[
]
Other sources
Low concentrations of dioxins have been found in some soils without any anthropogenic contamination. A puzzling case of milk contamination was detected in Germany. The source was found to be kaolin
Kaolinite ( ) is a clay mineral, with the chemical composition Al2 Si2 O5( OH)4. It is an important industrial mineral. It is a layered silicate mineral, with one tetrahedral sheet of silica () linked through oxygen atoms to one octahedral ...
added to animal feed. Dioxins have been repeatedly detected in clays from Europe and USA since 1996, with contamination of clay assumed to be the result of ancient forest fires or similar natural events with concentration of the PCDD/F during clay sedimentation.
Dioxins and biomass
In sugarcane cultivation, the remaining bagasse
Bagasse ( ) is the dry pulpy fibrous material that remains after crushing sugarcane or sorghum stalks to extract their juice. It is used as a biofuel for the production of heat, energy, and electricity, and in the manufacture of pulp and building ...
after extraction of sugar is used in large amounts for energy production (both process heat Process heat refers to the application of heat during industrial processes. Some form of process heat is used during the manufacture of many common products, from concrete to glass to steel to paper. Where byproducts or wastes of the overall indust ...
and electric energy for use both in the sugar factory itself and for other consumers), and locally it has been thought to be a remarkable source of dioxins. This basically indicates that burning biomass
Biomass is plant-based material used as a fuel for heat or electricity production. It can be in the form of wood, wood residues, energy crops, agricultural residues, and waste from industry, farms, and households. Some people use the terms bi ...
produces dioxins and it should be done at high enough temperatures and there should be proper filtering of flue gases. For the treatment of gases and pollutants, sugarcane industries often use wet gas scrubbers, such as the Venturi type. In addition, other treatment systems also used are electrostatic precipitator
An electrostatic precipitator (ESP) is a filterless device that removes fine particles, like dust and smoke, from a flowing gas using the force of an induced electrostatic charge minimally impeding the flow of gases through the unit.
In cont ...
s and bag filters. These methods may be insufficient Improperly burned biomass, which undergoes only low temperature incomplete combustion
Combustion, or burning, is a high-temperature exothermic redox chemical reaction between a fuel (the reductant) and an oxidant, usually atmospheric oxygen, that produces oxidized, often gaseous products, in a mixture termed as smoke. Combusti ...
, is responsible for much of the negative health effects of indoor air pollution and is a particular problem in the Global South
The concept of Global North and Global South (or North–South divide in a global context) is used to describe a grouping of countries along socio-economic and political characteristics. The Global South is a term often used to identify region ...
where biomass like wood or cowdung
Cow dung, also known as cow pats, cow pies or cow manure, is the waste product (faeces) of bovine animal species. These species include domestic cattle ("cows"), bison ("buffalo"), yak, and water buffalo. Cow dung is the undigested resid ...
are often the only commonly available fuels for cooking and home heating. In addition to dioxins, other harmful products of incomplete combustion - such as carbon monoxide
Carbon monoxide (chemical formula CO) is a colorless, poisonous, odorless, tasteless, flammable gas that is slightly less dense than air. Carbon monoxide consists of one carbon atom and one oxygen atom connected by a triple bond. It is the simple ...
- are also released when biomass is burned in low oxygen conditions. Using plastic, particularly chlorine-containing plastics such as polyvinyl chloride, as a fuel or firestarter further increases dioxin emissions.
Environmental persistence and bioaccumulation
All groups of dioxin-like compounds are persistent in the environment.[Claes Bernes: Persistent organic pollutants. Swedish Environmental Protection Agency, Stockholm 1998. .] Very few soil microbes nor animals can break down the PCDD/Fs with lateral chlorines (positions 2,3,7, and 8). This causes very slow elimination. However scientists at Martin Luther University
Martin Luther University of Halle-Wittenberg (german: Martin-Luther-Universität Halle-Wittenberg), also referred to as MLU, is a public, research-oriented university in the cities of Halle and Wittenberg and the largest and oldest university i ...
recently found that a type of bacteria ''Dehalococcoides
''Dehalococcoides'' is a genus of bacteria within class Dehalococcoidia that obtain energy via the oxidation of hydrogen and subsequent reductive dehalogenation of halogenated organic compounds in a mode of anaerobic respiration called organoha ...
'' CBDB1 can extract the chlorine from dioxin compounds in the absence of oxygen. Ultraviolet light slowly breaks down these compounds. Lipophilicity (tendency to seek for fat-like environments) and very poor water solubility make these compounds move from water environment to living organisms having lipid cell structures. This is called bioaccumulation
Bioaccumulation is the gradual accumulation of substances, such as pesticides or other chemicals, in an organism. Bioaccumulation occurs when an organism absorbs a substance at a rate faster than that at which the substance is lost or eliminated ...
. Increase in chlorination increases both stability and lipophilicity. The compounds with the very highest chlorine numbers (e.g. octachlorodibenzo-p-dioxin) are, however, so poorly soluble that this hinders their bioaccumulation.[ Bioaccumulation is followed by ]biomagnification
Biomagnification, also known as bioamplification or biological magnification, is any concentration of a toxin, such as pesticides, in the tissues of tolerant organisms at successively higher levels in a food chain. This increase can occur as a ...
. Lipid-soluble compounds are first accumulated to microscopic organisms such as phytoplankton (plankton of plant character, e.g. algae). Phytoplankton is consumed by animal plankton, this by invertebrates such as insects, these by small fish, and further by large fish and seals. At every stage or trophic level
The trophic level of an organism is the position it occupies in a food web. A food chain is a succession of organisms that eat other organisms and may, in turn, be eaten themselves. The trophic level of an organism is the number of steps it i ...
, the concentration is higher, because the persistent chemicals are not "burned off" when the higher organism uses the fat of the prey organism to produce energy.
Due to bioaccumulation and biomagnification, the species at the top of the trophic pyramid
An ecological pyramid (also trophic pyramid, Eltonian pyramid, energy pyramid, or sometimes food pyramid) is a graphical representation designed to show the biomass or bioproductivity at each trophic level in a given ecosystem.
A ''pyramid of ...
are most vulnerable to dioxin-like compounds. In Europe, the white-tailed eagle
The white-tailed eagle (''Haliaeetus albicilla'') is a very large species of sea eagle widely distributed across temperate Palearctic, Eurasia. Like all eagles, it is a member of the family Accipitridae (or accipitrids) which includes other diur ...
and some species of seals have approached extinction due to poisoning by persistent organic pollutants. Likewise, in America, the population of bald eagle
The bald eagle (''Haliaeetus leucocephalus'') is a bird of prey found in North America. A sea eagle, it has two known subspecies and forms a species pair with the white-tailed eagle (''Haliaeetus albicilla''), which occupies the same niche as ...
s declined because of POPs causing thinning of eggshells and other reproductive problems. Usually, the failure has been attributed mostly to DDT
Dichlorodiphenyltrichloroethane, commonly known as DDT, is a colorless, tasteless, and almost odorless crystalline chemical compound, an organochloride. Originally developed as an insecticide, it became infamous for its environmental impacts. ...
, but dioxins are also a possible cause of reproductive effects. Both in America and in Europe, many waterfowl have high concentrations of dioxins, but usually not high enough to disturb their reproductive success.[ Due to supplementary winter feeding and other measures also, the white-tailed eagle is recovering (see ]White-tailed eagle
The white-tailed eagle (''Haliaeetus albicilla'') is a very large species of sea eagle widely distributed across temperate Palearctic, Eurasia. Like all eagles, it is a member of the family Accipitridae (or accipitrids) which includes other diur ...
). Also, ringed seals in the Baltic Sea are recovering.
Humans are also at the top of the trophic pyramid, particularly newborns. Exclusively breastfed newborns were estimated to be exposed to a total of 800 pg TEQ/day, leading to an estimated body weight-based dose of 242 pg TEQ/kg/day. Due to a multitude of food sources of adult humans exposure is much less averaging at 1 pg TEQ/kg-day,[ and dioxin concentrations in adults are much less at 10-100 pg/g, compared with 9000 to 340,000 pg/g (TEQ in lipid) in eagles][ or seals feeding almost exclusively on fish.
Because of different physicochemical properties, not all congeners of dioxin-like compounds find their routes to human beings equally well. Measured as TEQs, the dominant congeners in human tissues are 2,3,7,8-TCDD, 1,2,3,7,8-PeCDD, 1,2,3,6,7,8-HxCDD and 2,3,4,7,8-PeCDF.] This is very different from most sources where hepta- and octa-congeners may predominate. The WHO panel re-evaluating the TEF values in 2005 expressed their concern that emissions should not be uncritically measured as TEQs, because all congeners are not equally important.[ They stated that "when a human risk assessment is to be done from abiotic matrices, factors such as fate, transport, and bioavailability from each matrix be specifically considered".][
All POPs are poorly water-soluble, especially dioxins. Therefore, ground water contamination has not been a problem, even in cases of severe contamination due to the main chemicals such as chlorophenols.] In surface waters, dioxins are bound to organic and inorganic particles.
Sources of human exposure
The most important source of human exposure is fatty food of animal origin (see Human intake, above),[ and breast milk.][ There is much variation between different countries as to the most important items. In U.S. and Central Europe, milk, dairy products and meat have been by far the most important sources. In some countries, notably in Finland and to some extent in Sweden, fish is important due to contaminated Baltic fish and very low intake from any other sources.][ In most countries, a significant decrease of dioxin intake has occurred due to stricter controls during the last 20 years.
Historically, occupational exposure to dioxins has been a major problem.][ Dioxins are formed as important toxic side products in the production of ]PCBs
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 t ...
, chlorophenols, chlorophenoxy acid herbicides, and other chlorinated organic chemicals. This caused very high exposures to workers in poorly controlled hygienic conditions. Many workers had chloracne
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 ...
. In a NIOSH
The National Institute for Occupational Safety and Health (NIOSH, ) is the United States federal agency responsible for conducting research and making recommendations for the prevention of work-related injury and illness. NIOSH is part of the C ...
study in the U.S., the average concentration of TCDD in exposed persons was 233 ng/kg (in serum lipid) while it was 7 ng/kg in unexposed workers, even though the exposure had been 15–37 years earlier.[ This indicates a huge previous exposure. In fact the exact back-calculation is debated, and the concentrations may have been even several times higher than originally estimated.]
Handling and spraying of chlorophenoxy acid herbicides may also cause quite high exposures, as clearly demonstrated by the users of Agent Orange
Agent Orange is a chemical herbicide and defoliant, one of the "tactical use" Rainbow Herbicides. It was used by the U.S. military as part of its herbicidal warfare program, Operation Ranch Hand, during the Vietnam War from 1961 to 1971. It ...
in the Malayan Emergency
The Malayan Emergency, also known as the Anti–British National Liberation War was a guerrilla war fought in British Malaya between communist pro-independence fighters of the Malayan National Liberation Army (MNLA) and the military forces o ...
and in the Vietnam War
The Vietnam War (also known by #Names, other names) was a conflict in Vietnam, Laos, and Cambodia from 1 November 1955 to the fall of Saigon on 30 April 1975. It was the second of the Indochina Wars and was officially fought between North Vie ...
. The highest concentrations were detected in nonflying enlisted personnel (e.g. filling the tanks of planes), although the variation was huge, 0 to 618 ng/kg TCDD (mean 23.6 ng/kg).[ Other occupational exposures (working at paper and pulp mills, steel mills and incinerators) have been remarkably lower.][
Accidental exposures have been huge in some cases. The highest concentrations in people after the Seveso accident were 56,000 ng/kg, and the highest exposure ever recorded was found in Austria in 1998, 144,000 ng/kg (see ]TCDD TCDD may refer to any of the following:
* Turkish State Railways
The State Railways of the Republic of Turkey ( tr, Türkiye Cumhuriyeti Devlet Demiryolları), abbreviated as TCDD, is a government-owned national railway company responsible with ...
).[ This is equivalent to a dose of 20 to 30 μg/kg TCDD, a dose that would be lethal to guinea pigs and some rat strains.
Exposure from contaminated soil is possible when dioxins are blown up in dust, or children eat dirt. Inhalation was clearly demonstrated in Missouri in the 1970s, when waste oils were used as dust suppressant in horse arenas. Many horses and other animals were killed due to poisoning.] Dioxins are neither volatile nor water-soluble, and therefore exposure of human beings depends on direct eating of soil or production of dust which carries the chemical. Contamination of ground water or breathing vapour of the chemical are not likely to cause a significant exposure. Currently, in the US, there are 126 Superfund
Superfund is a United States federal environmental remediation program established by the Comprehensive Environmental Response, Compensation, and Liability Act of 1980 (CERCLA). The program is administered by the United States Environmental Pro ...
sites with a completed exposure pathway contaminated with dioxins.
Further, PCBs are known to pass through treatment plants and accumulate in sludge
Sludge is a semi-solid slurry that can be produced from a range of industrial processes, from water treatment, wastewater treatment or on-site sanitation systems. For example, it can be produced as a settled suspension obtained from conventiona ...
which is used on farm fields in certain countries. In 2011 in South Carolina, SCDHEC enacted emergency sludge regulations after PCBs were found to have been discharged to a waste treatment plant.
PCBs are also known to flush from industry and land (aka sludge fields) to contaminate fish, as they have up and down the Catawba River in North and South Carolina. State authorities have posted fish consumption advisories due to accumulation of PCBs in fish tissue.
There have been several food contamination episodes, one of the best known occurred in Belgium
Belgium, ; french: Belgique ; german: Belgien officially the Kingdom of Belgium, is a country in Northwestern Europe. The country is bordered by the Netherlands to the north, Germany to the east, Luxembourg to the southeast, France to th ...
in 1999.[ A tank of recycled fats collected for animal feed production was contaminated by PCB oil containing about 1 g of dioxins and 2 g of DL-PCBs. This caused a major alarm in the European Union, but due to relatively fast response and slow accumulation of dioxins in humans there were no health impacts.][ There was a similar incidence in Ireland in 2008. In 2008, Chile experienced a pork crisis caused by high dioxin concentrations in their pork exports. The contamination was found to be due to zinc oxide used in pork feed, and caused reputational and financial losses for the country, as well as leading to the introduction of new food safety regulations.] These episodes emphasize the importance of food control, and early detection guarantees that very slowly accumulating dioxins do not increase in humans to levels causing toxic effects.
TEF values and toxicity equivalents
All dioxin-like compounds share a common mechanism of action via the aryl hydrocarbon receptor (AHR), but their potencies are very different. This means that similar effects are caused by all of them, but much larger doses of some of them are needed than of TCDD. Binding to the AHR as well as persistence in the environment and in the organism depends on the presence of so-called "lateral chlorines", in case of dioxins and furans, chlorine substitutes in positions 2,3,7, and 8.[ Each additional non-lateral chlorine decreases the potency, but qualitatively the effects remain similar. Therefore, a simple sum of different dioxin congeners is not a meaningful measure of toxicity. To compare the toxicities of various congeners and to render it possible to make a toxicologically meaningful sum of a mixture, a toxicity equivalency (TEQ) concept was created.][
Each congener has been given a toxicity equivalence factor (TEF).] This indicates its relative toxicity as compared with TCDD. Most TEFs have been extracted from ''in vivo'' toxicity data on animals, but if these are missing (e.g. in case of some PCBs), less reliable ''in vitro'' data have been used.[ After multiplying the actual amount or concentration of a congener by its TEF, the product is the virtual amount or concentration of TCDD having effects of the same magnitude as the compound in question. This multiplication is done for all compounds in a mixture, and these "equivalents of TCDD" can then simply be added, resulting in TEQ, the amount or concentration of TCDD toxicologically equivalent to the mixture.
The TEQ conversion makes it possible to use all studies on the best studied TCDD to assess the toxicity of a mixture. This is most useful in regulatory work, but it can also be used in scientific studies.] This resembles the common measure of all alcoholic drinks: beer, wine and whiskey can be added together as absolute alcohol, and this sum gives the toxicologically meaningful measure of the total impact.
The TEQ only applies to dioxin-like effects mediated by the AHR. Some toxic effects (especially of PCBs) may be independent of the AHR, and those are not taken into account by using TEQs.
TEFs are also approximations with certain amount of scientific judgement rather than scientific facts. Therefore, they may be re-evaluated from time to time. There have been several TEF versions since the 1980s. The most recent re-assessment was by an expert group of the World Health organization in 2005.
:(T = tetra, Pe = penta, Hx = hexa, Hp = hepta, O = octa)
File:2,3,7,8-substituted PCDD.svg, The 2,3,7,8-substituted PCDDs
File:2,3,7,8-substituted PCDF.svg, The 2,3,7,8-substituted PCDFs
File:Dl-PCB.svg, Dioxin-like PCBs
References
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Some content in this article was extracted fro
Dioxins and dioxin-like compounds: toxicity in humans and animals, sources, and behaviour in the environment
at the Wikiversity, which is licensed under th
Creative Commons Attribution-Share Alike 3.0 (Unported) (CC-BY-SA 3.0) license
External links
WHO fact sheet
Dioxins & Furans: The Most Toxic Chemicals Known to Science
Synopsis on dioxins and PCBs
{{Aryl hydrocarbon receptor modulators
Dioxins
Immunotoxins
Organochlorides
Endocrine disruptors