Encyclopaedia from D to O

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daily intake, the amount of a contaminant that an individual is exposed to during one day, usually via food (see PCB - sources, PCDD/F - sources).

DDT [1,1,1-trichloro-2,2-bis(4-chlorophenyl)ethane], a well known insecticide (insect killer). DDT is not related to PCBs or dioxins, but it is also chlorinated, persistent organic compound which bioconcentrates in the environment and may cause problems to wildlife. Both DDT and PCDD/Fs are supposed to be endocrine disrupters (see that).

deka-, ten. E.g., dekachloro- ten chlorine atoms in a molecule.

developmental toxicity, toxic effects occurring during the developing period, especially during embryonal stages of development. This period is often very sensitive to many chemicals, and the effect may range from reversible effects to embryonal or foetal death. Teratogenicity is one form of developmental toxicity, where a chemical causes permanent malformations. PCDD/Fs cause embryonal or foetal death at high exposures, teratogenicity such as cleft palate in some animal species, and they have been implied of being endocrine disrupters (see this).

di-, two. E.g., dichloro- two chlorine atoms in a molecule.

dibenzofuran, the parent compound of polychlorinated dibenzofurans (PCDFs), C₁₂OH₈. See chemical structures.

dibenzo-p-dioxin, the parent compound of polychlorinated dibenzo-p-dioxins (PCDDs), C₁₂O₂H₈. See chemical structures.

dioxane (1,4-diethylene dioxide), a ring-structured chemical, C₄H₈O₂. Used as stabiliser in chlorinated solvents and solvent for many organic compounds. Does not have dioxin-like effects.

dioxin, chemical name with multiple uses. In less careful language dioxin is used as a synonym of 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD), or any of the polychlorinated dibenzo-p-dioxins (PCDD) or dibenzofurans (PCDF), or the whole class of these compounds (see the specific entries). In strict chemical sense dioxin is a heterocyclic ring-structured chemical containing carbon, oxygen and hydrogen, C₄H₄O₂, forming e.g. the middle ring of dibenzo-p-dioxin (see chemical structures).

dioxin receptor. See AH receptor.

dioxin responsive element. See DRE.

diphenyl (biphenyl), the parent compound of polychlorinated biphenyls (PCBs), C₁₂H₁₀.

DNA (deoxyribonucleic acid), the basic chemical structure of the genes. It is formed of four bases, adenine (A), guanine (G), cytosine (C), and thymine (T), a sugar deoxyribose, and phosphate. Its structure was found in 1953 by James Watson and Francis Crick. The smallest unit of DNA is a nucleotide, which consists of one base, one sugar, and phosphate. The base distinguishes the four different nucleotides from each other. Three successive nucleotides form a codon, which is the smallest code word unit of DNA. One codon determines one amino acid (see this) when the message of DNA is translated to a protein. The execution of protein synthesis according to the "blueprint" in DNA is called expression of the gene. First a blueprint is copied to RNA (see this) by transcription and then according to the directions in codons, amino acids are linked to form a protein (see this) chain by translation.

DRE (dioxin responsive element, XRE, xenobiotic responsive element), a short sequence of DNA which binds the dimer of AHR+ARNT and initiates the transcription of a gene. The structure of DRE in the case of CYP1A1 gene is 5'-TNGCGTG-3'.

d.w., dry weight.

elimination of chemicals, mechanism to get rid of drugs and chemicals (see also PCB - elimination, PCDD/F - elimination). Elimination out of the body takes place in two principal ways: excretion and metabolism (usually followed by excretion of the breakdown products). Only water-soluble materials can be excreted in the kidneys to urine, and many organic pollutants are lipid soluble and poorly water-soluble chemicals. Therefore they cannot be excreted practically at all as such. Metabolism tries to make them more water soluble, but especially higher chlorinated PCBs (see PCB - physicochemical properties) and PCDD/Fs with "lateral" chlorine atoms (see this and PCDD - chemical structure, PCDF - chemical structure) are metabolised very poorly, and therefore cannot be effectively excreted even with the help of metabolism. They accumulate in body fats, and their half-life (see this) may be even several years. Elimination of drugs and chemicals usually obeys first order kinetics (see half-life, cumulation). This means that the rate of elimination directly correlates with the amount of the drug in the body (or the concentration in blood), i.e. a constant fraction (e.g. one per cent) of the chemical is eliminated in time unit (e.g. in an hour).

embryo, unborn offspring during the period of most rapid development until all major structures (limbs, inner organs) are represented, in man from two weeks after fertilization to the end of seventh or eighth week (see also foetus).

endocrine disrupters, chemicals or natural compounds that can interfere with the actions of hormones. Such chemicals have been known for decades, e.g. natural goitrogens (compounds in many plant species of Cruciferae-family that interfere with thyroid hormone synthesis), and many drugs that cause changes in the levels of pituitary hormone prolactin. Some PCBs and their metabolites bind to thyroid hormone binding protein and interfere with its function. Presently there is interest in many countries in chemicals that might interfere with the activity of sex hormones. p,p'-DDE, a metabolite of DDT is an antiandrogen: it antagonizes the effects of testosterone (male sex hormone). Estrogenic (female sex hormone) and antiestrogenic risks from the environment are less well characterised, but environmental chemicals have been implied to cause "feminisation" or "demasculinisation". In waterways the most important estrogenic compounds (e.g. causing sexual disturbances in fish) seem to be natural estrogens from humans and animals, and synthetic estrogens from contraceptive pills. Synthetic chemicals with postulated endocrine disrupting activity include phthalates, bisfenols, alkoxyphenols, organochlorine insecticides, some detergents, PCBs, and PCDD/Fs. Their effects on human male disorders (such as testis cancer, hypospadias, and semen quality) are under investigation, but so far there is no unambiguous evidence.

environmental persistence, ability of a chemical to continue existence in the environment (see PCB - environmental persistence, PCDD/F - environmental persistence.

epigenetic carcinogens, chemicals that cause tumours without causing mutations or other genetic damage. Instead they act by e.g. promoting the multiplication the initiated tumour cell and the growth of a tumour (see also mutagenicity and promoters).

equivalency factors. See TEF.

EU directives on dioxin. See PCDD/F - limit values.

expression of a gene, reading a genetic information from DNA to make a new protein (see DNA and RNA). Every cell contains every gene of the individual, but only some are expressed in any particular cell, and often only at a particular time. Proteins involved e.g. in the synthesis of skin pigment are expressed only in certain layers of the skin, and not in the gut; even in the skin the rate of expression depends on the stimulation by sunlight.

extrapolation, extending predictions outside the range of observations. In regulatory toxicology extrapolation means predicting an effect in such conditions that it is not possible to assess the effect experimentally. Extrapolation is used over dose, species, sex, age, or route.
Dose extrapolation means predicting an effect (e.g. the likelihood of cancer) below the range of doses that can be tested experimentally. In a group of 50 animals in a two-year cancer study, it is possible to detect a 10 % additional cancer risk, i.e. five cancers in addition to the typical background incidence of e.g. ten cancers. Ten per cent risk would be clearly unacceptable in humans. We would barely accept a risk of one in ten thousand of contracting cancer from a chemical. However, an experiment that could detect an increase in cancer risk from 20 % (background) to 20.01 % (background + chemical-induced) would need more than 100,000 animals. This is clearly not feasible. Therefore the dose of the chemical is increased so that the effect is detectable, and the effect at the true level of human exposure is extrapolated mathematically. Because there is no obvious way to prove the correct formula for extrapolation, this is one of the most common sources of disputes in toxicology (see also linear extrapolation).
Another extrapolation is species extrapolation. If the chemical is studied in the mouse, one need to know what dose in the mouse is equivalent to a dose in humans. This is one of the sources of confusion in dioxin risk assessment, because TCDD kills a guinea pig at a dose of 0.001-0.002 mg/kg, but a hamster only at a dose of several mg/kg. So it is important to know, which is a better model for human being, the guinea pig or the hamster. Some effects of TCDD, such as developmental toxicity, are seen at low doses both in guinea pigs and hamsters, however.

Fenchlor, a commercial PCB product. See PCB - trade names.

first order kinetics, see elimination.

foetus, fetus, unborn offspring after all major structures have been outlined, in man from seven or eight weeks after fertilization until birth (see also embryo).

gas chromatography-mass spectrometry (GC-MS), a method for analysing concentrations of, e.g., PCDD/Fs, PCBs, and other organic compounds in a sample. The method has two phases: first, separation based on differential movement of compounds in hot flowing gas in a long quarz capillary; second, detection based on the molecular mass of the compounds. The method is very sensitive and it can detect amounts as low as 0.5 - 100 pg, depending on the resolution of mass spectrometer and the matrix.

GC-MS. See gas chromatography-mass spectrometry.

genotoxic carcinogens, cancer-causing substances that cause mutations, chromosomal damage or other kind of damage to the genetic material in cells. They are thus able to transform a normal cell to a cancer cell (see mutagenicity).

geological sources. See natural sources.

half-life, time needed to decrease the amount of chemical to one-half (see also PCB - half-life, PCDD/F - elimination). Most chemicals are eliminated out of the body by the so-called first-order elimination. This means that a fixed proportion (e.g. one per cent) of the chemical remaining in the body is eliminated per unit of time (e.g. per hour). Therefore when the concentration in the body is high, more is eliminated in absolute terms (e.g. milligrams of chemical) than later when the concentration has already decreased. A convenient measure for the rate of elimination is the half-life: this is the time during which the amount of chemical in the body will decrease to 50% of the amount in the beginning of the observation. The half-life is a constant for a chemical, so during the first half-life the amount decreases to 50%, during the next to 25%, during the next to 12.5% and so on. As a practical rule it is considered that a substance is totally eliminated within 5 half-lives (in fact about 3% of it still remains). Elimination half-life is equal to cumulation half-time. This means that with a constant intake, body burden increases practically 5 half-lives, after which a steady state is achieved.

hepta-, seven. E.g., heptachloro- seven chlorine atoms in a molecule.

herbicides, see chlorophenoxyacetic acid herbicides.

hexa-, six. E.g., hexachloro- six chlorine atoms in a molecule.

HpCDD, heptachlorodibenzo-p-dioxin. See chemical structures.

HpCDF, heptachlorodibenzofuran. See chemical structures.

HxCDD, hexachlorodibenzo-p-dioxin. See chemical structures.

HxCDF, hexachlorodibenzofuran. See chemical structures.

incinerator, a furnace to burn completely waste materials. Incinerators of mixed municipal waste are one of the most important sources of PCDD/Fs in Western Europe. PCDD/Fs are formed, if there is chlorine (especially from polyvinyl chloride plastics, PVC) and certain metals present which catalyse their formation, and thermal conditions are favourable. Incinerators may also vaporise PCDD/Fs, PCBs and their contaminants from the fuel, if the burning conditions are not adequate. Incinerating is a completely valid means of disposing of PCDD/Fs (and PCBs), but the requirements of the incinerator are quite demanding. The temperature must be high enough, and there must be a proper filtering system to collect fly ash that may still contain some PCDD/Fs formed after cooling. It should be noted that dioxins may be formed during any unfavourable combustion process, if the required materials are present, including motor vehicles and small-scale burning of mixed materials (see also combustion).

I-TEq (international TCDD-equivalent quantity), see TEq.

IUPAC, International Union of Pure and Applied Chemistry. IUPAC has standardised the names of all PCB and PCDD/F congeners and given them reference numbers that are widely used due to their simplicity compared to their proper names. E.g., PCB126 denotes 3,3',4,4',5-pentachlorobiphenyl.

Kanechlor, a commercial PCB product. See PCB - trade names.

lateral chlorines, the four chlorine atoms in a PCDD/F molecule in positions 2, 3, 7, and 8 (see chemical structures). These four chlorines are required for binding to the AH receptor and toxic effects. They also stabilise the molecule against metabolism, which increases their half-life and tendency for accumulation. PCDD/Fs without lateral chlorines are rapidly metabolised, which prevents their accumulation in the food chain.

LD50 (median lethal dose), a dose which is lethal to 50 % of animals usually in an acute experiment (a single dose experiment).

levels of dioxins, see PCDD/F - concentrations in humans and body burden.

linear extrapolation, a straight-line projection of an effect to smaller doses (see also extrapolation). Linear extrapolation is a simple way of quantifying a toxic effect (usually cancer) at low doses, which cannot be tested reliably. Cancer rate is measured at a high dose, and found to be e.g. 10 % (a cancer in every tenth animal). An assumption is made that the rate decreases towards low-dose range linearly at the same rate as the dose. In other words, one hundredth dose gives the number of tumours that is one hundredth of the measured number (one hundredth of 10 % is then one out of 1000), and so forth. Linear extrapolation means that there is no safe dose ("one molecule can cause a cancer"). While intuitively attractive, this theory is probably false thanks to our defence mechanisms, and carcinogenicity is not different from any other form of toxicity. The actual risk is probably lower than the estimate achieved by linear extrapolation, hence this method is conservative. In theory also one tuberculosis bacillus can cause the disease, but experience has taught us that the dose of bacteria is highly relevant, and in real life one bacillus is easily destroyed by the body and cannot cause tuberculosis.

lipids, one of the principal classes of macromolecules in our body (the others are proteins and carbohydrates). Lipids include fats and oils (triglycerides), fatty acids, waxes, steroids, phospholipids, glycolipids and lipoproteins.

lipophilicity, having a strong affinity to fats and other lipids (rather than to water). This property of a chemical is often described by the octanol-water partition coefficient P_ow. It is the proportion of the concentrations of the dissolved chemical in octanol (a lipophilic solvent) and water phases in a test tube. The more lipophilic chemical, the more it moves to the octanol phase and the higher the P_ow value.

LOEL (LOAEL), lowest observed (adverse) effect level. A common term in regulatory toxicology to define the lower limit of toxic or biochemical effects in animal studies. This time-honoured term is a poor and inaccurate way of defining toxicity, because toxicity is not a threshold phenomenon but fades away gradually when the dose decreases. Therefore LOEL depends on the number and size of doses selected, number of animals (the more animals, the lower the LOEL is likely to be), and inaccuracy caused by chance. Errors can be easily an order of magnitude (tenfold) or greater. There is a trend to replace LOEL with a "benchmark dose", which is defined as a dose causing 5 % or 10 % of the maximal effect. It is much more accurate, because it is not based on just one dose but a dose response curve derived from several dose levels.

Love Canal, a residential area at Niagara Falls, New York. Housing and a school were constructed over an old hazardous waste site containing many chemicals including dioxins. This was revealed in 1979, and the population evacuated. There is no unambiguous evidence of human illness due to this incident.

metabolism, processes by which a particular substance is handled in the body. Chemical transformation of foreign chemicals (xenobiotics) occurs especially in the liver, but to some extent in all tissues. Usually the main purpose is to transform the chemicals to a more water-soluble form so that they can be excreted via urine or faeces. Often this drug or xenobiotic metabolism occurs in two steps, in the first phase usually oxidative enzymes attach a "handle", a suitable group such as hydroxyl, to the chemical, and secondly a water-soluble molecule (such as a sugar or amino acid) is tied to this handle to increase water-solubility. Often the metabolised products are less toxic, but in occasional cases metabolism may increase toxicity.

microgram (µg), 0.000,001 g. See units.

mono-, one. E.g., monochloro- one chlorine atom in a molecule.

mono-ortho-PCB. See ortho-PCB.

municipal waste incineration. See incinerator.

mutagenicity, a property of a chemical to cause genetic damage (damage of DNA). If the error is caused to a critical gene (such as in a so-called proto-oncogen or "cancer gene", or in an anticancer gene), the result may be carcinogenicity. Therefore mutagenicity tests are done as cheap preliminary tests to assess the possibility of cancer risk of a chemical. PCBs and PCDD/Fs are not mutagenic, and thus they are not likely to initiate a cancer, but they may promote the development of cancer initiated by other factors.

nanogram (ng), 0.000,000,001 g. See units.

natural sources of dioxins, sources not associated with human activities. Few exhaustive analyses have been performed on old samples, but it seems on the basis of both soil samples in museums and sea and lake bottom sediment samples that pre-industrial PCDD/F levels are detectable but low. These may be due to forest fires and later due to combustion of natural items such as wood and peat. A drastic increase is seen after 1940's, and this coincides with a change in congener profiles. PCBs are not detected in pre-industrial samples.

ng, nanogram. See units.

NOEL (NOAEL), no-observed-(adverse)-effect level. The largest dose in an animal experiment that does not cause an effect (see LOEL).

nona-, nine. E.g., nonachloro- nine chlorine atoms in a molecule.

non-ortho-PCB, see ortho-PCBs.

OCDD, octachlorodibenzo-p-dioxin. See chemical structures.

OCDF, octachlorodibenzofuran. See chemical structures.

octa-, eight. E.g., octachloro- eight chlorine atoms in a molecule.

octanol, octyl alcohol, C₈H₁₇OH.

ortho-PCBs, congeners of PCBs that have one or more chlorines in ortho-position (positions 2 or 6; see chemical structures). Position of a group in aromatic ring as related to some other group can be ortho-, meta- (positions 3 or 5), or para- (position 4). In PCB congeners (see congener) this is counted from the carbon-carbon bridge between the two phenyl rings. ortho-Congeners mean congeners that have one (mono-ortho) or several (di-ortho, tri-ortho, tetra-ortho) chlorines in ortho positions. ortho-Positions affect the conformation of the molecule; non-ortho PCBs can assume a completely flat (planar) conformation, which is close to that of dioxins. Space-requiring ortho chlorines are a steric hindrance for the flat conformation, and therefore only non-ortho or to some extent mono-ortho PCBs can mimic PCDDs to have similar toxic effects based on binding to AH receptor (see this). Chlorines in para-positions seem to be preferably biodegraded. This means easier degradation of non-ortho congeners, and ortho-congeners are present in the environment at higher concentrations than non-ortho congeners.
 
 

Contents of the Synopsis

Information on the publication
General introduction

Burning produces dioxins
Dioxins and some PCBs cause multiple toxic effects.
Dioxins and PCBs accumulate in the human body.
Risk assessment is tricky.
Common sources of errors and practical difficulties.

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Version 0.2 updated 17.9.1999 Jouni Tuomisto