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Σ (sigma), sum. Ordered alphabetically at the main entry disregarding the prefix (e.g. Σ7PCB, see PCB).

absorption, uptake of digested nutrients or any chemical from the site of the first entry to the organism proper. The most common site of absorption is the gastrointestinal tract: stomach and the gut. Any unabsorbed material in the contents of the gastrointestinal tract is in principle outside the body. Therefore absorption is the first critical step towards toxicity of any chemical. The absorption of fat-soluble and poorly water-soluble dioxins and PCBs depends on the presence of fats: they are absorbed easily if they are dissolved in fats, but often poorly, if they are e.g. adsorbed onto soil material.

accumulation. See cumulation.

acute toxicity, short-term toxicity usually after a single dose of a chemical. This is usually measured during the observation period of 24 hours or sometimes up to 2 weeks, but in the case of PCBs and PCDD/Fs it must be observed for 4 or 6 weeks (see PCB - acute toxicity, PCDD/F - acute toxicity).

adsorption, attachment of material to a surface. In soil and sediments dioxins and PCBs adsorb tightly to the surface of organic material or clay particles, and may be poorly available for living organisms.

Agent Orange. See chlorophenoxyacetic acid herbicides.

AH receptor (AHR, dioxin receptor, aryl hydrocarbon receptor), a cell protein that initiates many of the effects of dioxin-like chemicals. Its primary function in the body is uncertain, and it is structurally related to many other important cell proteins involved for instance in rhythmic functions (clock proteins) and organ development.
Mechanism. When TCDD or other dioxins enter the cell, they bind to AHR, this moves from cellular cytoplasm to nucleus, forms a pair with another protein ARNT (see this), and this heterodimer (complex of two separate proteins) binds to DNA (see this). This binding initiates the activation of a number of genes depending on the binding site of the dimer. Because it initiates the reading of a gene (transcription), it is called a transcription factor (see this). One of the best studied of such genes is the gene of CYP1A1 enzyme, which is a xenobiotic metabolising enzyme. CYP1A1 oxidises many foreign chemicals and makes them more water-soluble. Activation of its gene increases the enzymatic activity even by a factor of several hundreds. It is not known which gene is (genes are) responsible for the toxic effects of dioxins (for more information on AHR, see Okey et al., Toxicol. Lett. 1994:70:1-22).

AH receptor nuclear translocator, see ARNT.

amino acid, the elementary unit of proteins. There are 20 common amino acids in proteins, and their order determines the character of the protein just as the order of the 26 letters of alphabet determines the contents of this text.

analysis, see PCB - analysis, PCDD/F - analysis.

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

ARNT (Ah Receptor Nuclear Translocator), a protein in cell nucleus which acts as a partner of AH receptor (see this) and some other transcription factors. The complex of AHR + ARNT is called heterodimer, because it is a dimer of two different proteins. ARNT is in fact a misnomer, since it was previously thought to translocate AHR from the cytoplasm of the cell to the nucleus, but in fact it only binds AHR after this has entered the nucleus.

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

aryl hydrocarbon receptor, see AH receptor.

Baltic Sea, an important sink of PCBs and PCDD/Fs in Europe. PCBs may have come mainly as air-borne pollution from Western Europe (see PCB - sources, and incinerators). PCDD/Fs (especially higher chlorinated PCDFs) may have their origin also in forest industries and their use of chlorophenols (see this). The levels in the Baltic Sea peaked during the 1970s, and have been decreasing since, albeit slowly. Baltic levels have caused a number of environmental toxicological effects, e.g. reproduction problems of seals and eagles (for more information, see Bernes, C.: Persistent Organic Pollutants, Monitor 16, Swedish Environmental Protection Agency, 1998).

Belgian chicken incident, a food contamination incident in Belgium. In January 1999 a large tank of recirculated fats was contaminated probably by PCB oil. Refined fat was sold to more than ten animal feed factories (the contaminated lot probably only to two factories, both in Belgium), which again sold their contaminated feed to farms, mostly chicken farms. The problem was noticed when the chickens showed symptoms of toxicity: low fertility and deformed chicks.
The contamination of chicken feed is essentially a PCB problem, not a primary dioxin problem. The amount of PCB oil, causing the measured concentrations in the animal feed need not be more than about 10 litres. This could be the content of one or a few transformers.
The highest concentrations of PCBs found in chicken fat have been 51 mg/kg (Σ7PCB in fat) (51,000 ng/g) (see seven marker PCBs), and the highest dioxin concentration 0.0026 mg/kg (2,613 ng/kg, as I-TEq or TCDD-equivalents in fat). PCBs have later (in summer 1999) been found also in pork, but not in milk at concentrations above the general background. In chicken or chicken feed samples there were 50,000 times more PCBs (Σ7PCB) than dioxin-TEqs, and the ratio is fairly constant. This means that monitoring in this specific case can be based on PCBs. As a screening analysis this can be performed in many laboratories, whereas dioxin analysis is extremely difficult and there are very few laboratories in Europe capable of performing them reliably. Also the cost of dioxin analysis is prohibitively expensive (of the order of 1000 euro per sample) and the analysis is time-consuming (about 1 month). Therefore routine monitoring cannot be based on dioxin analyses or congener-specific PCB analysis using mass spectrometry.

 
 

Figure 1. Modelled increase in the body burden of a person who consumes continuosly the worst-contaminated chicken from Belgian chicken incident. A, six-month follow-up; B, 70-year follow-up. Assumptions: half-life: 8.6 years, body fat content: 15 kg, PCDD/F concentration in chicken: 1000 ng/kg (TEq in fat), chicken fat content: 15 % (per wet weight).

Belgian PCB incident - risk evaluation. Dioxin concentrations that exceed the accepted limits in extreme cases by a hundredfold or more would cause a highly increased body burden in human beings, but slowly. Consuming 150 g of contaminated chicken (assuming 1000 ng/kg I-TEq in fat, 15 % of fat in the meat) twice a week would produce a body burden that would be hundredfold as compared with the present body burden of population (Figure 1). This would, however, require a continuous consumption during 30 to 50 years (see cumulation). In fact, an increase of 20 ng/kg (I-TEq in fat) would require 1 to 2 months of continuous consumption. Because the average young adult concentration in Central Europe in the period 1987 to 1993 decreased from 40 ng/kg to 20 ng/kg, the calculated consumption for one month would mean going back to the levels prevalent in population during the 1980s.
Because it is unlikely that an individual would consume the worst contaminated chicken from week to week at this level, the true population effect is much less. There may, however, be individuals who eat contaminated products from a single farm for some reason, and among those this prediction might hold. Even in such a case the time factor excludes any dramatic effects of dioxins. The contribution of non-dioxin-like PCBs is more difficult to assess. Particularly their poorly characterised neurodevelopmental effects are of concern. Also these compounds accumulate slowly.
The incident shows that due to the slow cumulation of dioxins, long-term control of food is of paramount importance, and probably should be reconsidered in the European Union. It also seems that the recirculation and reuse system of fats, which as such is ecologically sound in reducing waste, is too open and vulnerable.
This risk evaluation means that food control should be very strict, and monitoring of concentrations in exposed population groups are highly advisable, but no individual health measures in those people who have consumed contaminated chicken for a limited time period can (nor need to) be recommended.

bioaccumulation (bioconcentration), property of a chemical to be concentrated from the surrounding environment to living organisms. Lipid-soluble, poorly water-soluble chemicals seek any lipid-containing material especially in water environment, e.g. plankton. Bioconcentration is strictly speaking a passive partition or diffusion between the media and the organism, bioaccumulation may also encompass uptake of compounds via feeding.

bioavailability, portion of a drug or chemical to enter the organism in active form. Bioavailability may be lowered by poor absorption or by metabolism in the gut or liver before passing to blood stream.

biomagnification, property of a chemical to be concentrated along the food chain. This requires that the chemical is not easily degraded chemically or biologically, and that it is bound to organisms or tissues so that it is carried from one species to the next species using it as its food. Lipid-soluble, poorly water-soluble chemicals are bioaccumulated by e.g. phytoplankton (plankton of plant character such as algae), this is consumed by animal plankton, this by invertebrates, further by fish and finally by seals. If the lipid-soluble chemical is very persistent, its concentration will increase stepwise at each level. That is why the species at the "top" of a feeding pyramid suffer most of persistent environmental chemicals. Chlorination of organic chemicals often increases both their persistence and their lipid solubility. Therefore PCBs and dioxins are bioaccumulated and biomagnified especially well. Increasing number of chlorines increases both lipid solubility and biomagnification. However, the optimal biomagnification capacity is at about 6 chlorines, probably because higher chlorinated congeners (esp. octa-) are so poorly water soluble that their bioavailability is low. Human beings are also at the top of the food chain, but because of the variety of foods from different sources humans consume, as compared with seals or eagles, bioaccumulation to humans is not so great.

biphenyl, C₁₂H₁₀, parent compound of polychlorinated biphenyls. See chemical structures.

body burden, the total amount of a chemical in the body. Average body burden of total sum of PCBs in industrialised countries range from less than 10 mg to 50 mg (ΣPCB) per person (less than 1 to 5 mg/kg [ΣPCB in fat]). Average daily intake of the sum of PCBs is 0.2 µg/kg b.w. or 14 µg per person. Average body burden of dioxins in young western European population is 100-200 ng (TEq) per person (0.000,000,1 - 0.000,000,2 g [TEq]); it can also be expressed as 10-20 ng/kg (TEq in fat) (Figure 2), in 60-year-old population 500-1000 ng (TEq per person). In steady state (see this) the body burden is about 5000 times the daily intake of dioxins. Average daily intake in many countries (see also PCDD/F - sources) is 1 to 2 pg I-TEq/kg b.w. or about 100 pg (0.1 ng or 0.000,000,000,1 g) per person (note that PCBs are given as the total sum of congeners whereas PCDD/Fs are given as TEq, see TEq and units).

 
 

Figure 2. PCDD/F body burden in some countries measured from human milk samples of primipara mothers. (Data from the second round of WHO-coordinated exposure study, 1993.)

breast milk, one of the most important sources of dioxins and PCBs. Breast milk contains many lipid-soluble materials that are present in mother's adipose tissue. In fact the concentrations of PCBs and PCDD/Fs are almost identical in mother's adipose tissue, serum lipid and breast milk fat. This is an effective excretion method for the mother, who can lose even 25 % of her body burden of these substances during a long breast-feeding period. However, 25 % of mother's body burden is then concentrated to a much smaller body, that of the baby. Therefore breast-fed babies are an obvious high-risk group for PCBs and PCDD/Fs. The dilemma of a risk assessor is that it is known with certainty that breast-feeding is beneficial for the baby, but there is no certainty that these chemicals would cause any harm at their present concentrations. Therefore most international expert groups have emphasised the importance of breast feeding and considered that whatever risks the dioxins may cause, they are not greater than the risks of not using the health advantages of mother's milk with its nutritional value, immunologically useful proteins and other health promoting factors.

b.w., body weight.

carcinogenicity, a property of a chemical to cause cancer. It is also called tumourigenicity to emphasise that a chemical may cause benign tumours and malignant tumours (such as carcinoma). Carcinogenic chemicals are often divided to genotoxic carcinogens (initiators) that can cause mutations (see mutagenicity) and initiate a cancer cell, and epigenetic carcinogens (see promoters) that are able to promote growth and/or differentiation of existing cancer cells.

carcinogenicity of dioxins, see PCDD - carcinogenicity and PCDF - carcinogenicity.

carcinogenicity of PCBs, see PCB - carcinogenicity.

carcinogenicity of PCDFs, see PCDF - carcinogenicity.

chemical structures. PCBs consist of 12 carbon atoms, forming two aromatic phenyl rings attached to one another through a carbon-carbon bridge, and 10 atoms that can be either hydrogens or chlorines (Figure 3). Theoretically 209 various combinations of chlorine and hydrogen are possible, and about 130 may be found in technical products. They are called congeners (see also ortho-PCBs). Chlorine increases the stability and decreases flammability of these compounds. The two phenyl rings of PCBs are able to rotate along the carbon-carbon bridge axis, and therefore they are flexible in the sense that they can assume a planar (flat) conformation similar to PCDDs, or a propeller-like conformation. ortho-Chlorines (in positions 2 and 6) may, however, prevent the planar conformation to a variable degree, and therefore ortho-congeners are less dioxin-like than non-ortho-congeners (see ortho-PCBs). Commercial PCBs contain PCDFs at levels up to 40 mg/kg, but usually not PCDDs. 
 

PCDDs consist of 12 carbon atoms, forming two aromatic phenyl rings attached to one another through two oxygen bridges, and 8 atoms that can be either hydrogens or chlorines (Figure 4). Theoretically 75 various combinations of chlorine and hydrogen are possible, and the resulting dibenzo-p-dioxin derivatives are called congeners (see this). Chlorine increases the stability of these compounds, and chlorines in positions 2,3,7, and 8 (lateral chlorines) are especially important, because they are essential for toxicity and also prevention of enzymatic destruction of PCDDs. Therefore the 7 congeners with 2,3,7,8-structure are toxicologically the most relevant. All additional chlorines to 2,3,7,8-structure decrease toxicity, but the spectrum of adverse effects remains similar (see TEF). Tetra-, penta-, hexa-, hepta-, and octachloro-derivatives are often called TCDD, PeCDD, HxCDD, HpCDD and OCDD, respectively.
 

PCDFs consist of 12 carbon atoms, forming two aromatic phenyl rings attached to one another through one carbon-carbon bond and one oxygen bridge (Figure 5), and 8 atoms which can be either hydrogens or chlorines. Theoretically 135 various combinations of chlorine and hydrogen are possible, and the resulting dibenzofuran derivatives are called congeners. Chlorine increases the stability of these compounds, and chlorines in positions 2,3,7, and 8 (lateral chlorines) are especially important, because they increase toxicity and also prevent enzymatic destruction of PCDFs. Therefore the 10 congeners with 2,3,7,8-Cl-structure are toxicologically the most relevant. Most additional chlorines to 2,3,7,8-structure decrease toxicity (see TEF), but the spectrum of adverse effects remains similar. Tetra-, penta-, hexa-, hepta-, and octachloro-derivatives are often called TCDF, PeCDF, HxCDF, HpCDF and OCDF, respectively.
 

chloracne, a severe acneiform skin disease that is seen in humans after high industrial or accidental exposure to chlorinated compounds, esp. dioxins. A threshold level above which chloracne occurs has not been established. The dose range where chloracne was reported in Seveso, was 800 to 56,000 ng/kg (TCDD in fat), but some persons with levels up to 10,000 ng/kg did not have chloracne.

chlorophenols, a group of chemicals derived from phenol by chlorination. They are used mainly as antifungal impregnation agents in wood preservation, but previously their use has been widespread. The most common preparation is pentachlorophenol. Also tetrachlorophenol is the main chlorophenol in some preparations. Chlorophenols contain several other chlorinated compounds as minor contaminants, including PCDD/Fs. Chlorophenols may be a remarkable source of PCDD/Fs in waterways downstream of forest industries. In the most contaminated regions, the concentration of PCDDs and PCDFs in soil and sediments appears to be incredibly high, up to 10 mg/kg (10,000,000 ng/kg) dry weight, and as I-TEq 0.1 mg/kg dry weight (100,000 ng/kg). Chlorophenols have been banned in many European countries but not in all, and large amounts may exist in soil and sediments even after the discontinuation of their use. Some chlorophenols (esp. 2,4,5-trichlorophenol) were intermediates for further synthetic work.

chlorophenoxyacetic acid herbicides, a major class of weed-killers. They were once the most important class of herbicides, but their role has been decreasing. Some of them contained PCDD/Fs, 2,4,5-T in fact contained TCDD at relatively high concentrations during the 1970s. 2,4,5-T gained notorious reputation as an antifoliant agent (Agent Orange) in Vietnam War. It has later been claimed to have caused a number of side effects, including cancer and birth defects. Large epidemiological studies have not been able to substantiate these claims, but doubts have lingered ever since. Also Swedish studies suggested increased cancer rates (soft-tissue sarcomas and non-Hodgkin lymphomas) in forest workers and others using these herbicides. Studies from other countries have not substantiated the high risk levels published in Sweden, but the most recent studies suggest some occupational risk. It is not completely clear whether this would be due to the herbicide itself or to dioxin impurities (for details, see Kogevinas et al., Am. J. Epidemiol. 1997:145:1061-1075).

citrus pulp pellet incident, a cattle feed contamination incident in 1997 and 1998. PCDD/F-contaminated lime was used in the drying process of pellets in one orange juice factory in Brazil. Pellets (dried orange peel) were imported to many European countries, especially France, Belgium, the Netherlands, and Germany, and fed mainly to cattle. In Germany, a steady increase in dioxin concentrations in cow's milk was observed: average values were 0.62 ng/kg (I-TEq in fat) before August 1997; between September and December, 0.89; between January and February 1998, 1.38; and in March, up to 7.4 ng/kg (I-TEq in fat). The pellets were found to be the source of the contamination in April 1998.
The import of pellets from Brazil was banned for months, and a program for preventing further pellet contamination was set up. A provisional maximum level for PCDD/F in citrus pulp pellets was set at 0.5 ng/kg (I-TEq in d.w.) in EU. A major part of the feed was drawn from the market and destroyed. The total amount of the contaminated pellets was ca. 100,000 tons. A relatively small amount of heavily contaminated pellets had been mixed with this large stock during transportation, hence the concentrations varied greatly. The typical concentrations of PCDD/Fs in citrus pulp pellets were below 10 ng/kg (I-TEq in d.w.), but the highest concentrations were up to 32 ng/kg (I-TEq in d.w.).

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

combustion, one of the major sources of PCDD/Fs. PCDD/Fs are formed during any unfavourable combustion process, if the required materials (chlorine, carbon, and certain metal catalysts) are present. This includes municipal waste incinerators, but also motor vehicles and small-scale burning of mixed materials. Especially unfavourable burning conditions prevail in accidental fires of landfill areas of municipal waste. On the other hand, a first-class incinerator (limit value 1 ng/Nm³ [I-TEq in exhaust gases], obtained by high enough burning temperature, good mixing, long enough residence time for burning gases, and "scrubbing" of the effluent gases to remove fly ash effectively) is an effective ultimate way to remove dioxin-like compounds from the environment.

congeners, chemicals derived from the same parent compound. PCBs, PCDDs and PCDFs are all mixtures of closely related compounds which are derivatives of biphenyl, dibenzo-p-dioxin and dibenzofuran, respectively (see chemical structures). Various number of hydrogen atoms in these parent compounds have been replaced with chlorine atoms, producing 209 possible PCBs, 75 possible PCDDs and 135 possible PCDFs. Derivatives in each group are called congeners in relation to other members of the same group. 17 PCDD/F congeners (7 PCDDs and 10 PCDFs) have "lateral" chlorines in positions 2,3,7 and 8, and are commonly measured and summed up by using TEq concept (see this). Similarly PCB-TEqs are used for "dioxin-like" non-ortho or mono-ortho PCB congeners (see ortho-PCBs).

conservative risk assessment, type of risk assessment which maximises the expectation of risk in order to make sure that the true risk is always below the estimate. In risk assessment one has often to act in the state of uncertainty. Because many risk assessors prefer to err in the direction of exaggerating the risk rather than in the direction of not appreciating the risk, the worst possible prediction is often taken as the basis of risk evaluation in different steps of risk assessments. An example is using 95 % upper confidence limit rather than the most probable (average) risk level as the basis of likelihood of a deleterious effect. Another example is the so called linear extrapolation (see this) of cancer. It means that at one tenth dose of a carcinogenic chemical the number of cancers is also assumed to decrease to one tenth, at one hundredth dose to one hundredth, and so on all the way to zero level. An alternative way would be to assume a safe dose below which there is no cancer any more. Neither way of evaluation can be scientifically proved to be correct, but in conservative risk assessment the worst possibility is taken to be true. Conservative risk assessment has been criticised on several grounds. One is that crying the wolf all the time will inflate the message. The other point is an imbalance of risk evaluation, because conservative risk assessment is possible in some areas, e.g. in pesticide or dioxin risk assessment, but not in others such as air pollution or alcohol. This then may lead to wrong priorities, e.g. to overemphasising pesticide or dioxin risks while neglecting air pollution risks. Thirdly, the more uncertainty there is in the estimate, the higher the final estimate tends to be, while accurate estimates with little uncertainty tend to be lower. This results in systematic underrating of well-known risks, even if they were relatively high.

cumulation, accumulation of a drug or chemical in the body. If a chemical enters the body continuously, its amount in the body increases until the elimination will reach the same rate as the intake; in other words the same amount of chemical is eliminated per unit of time as is entering the body. This is called the steady state. If elimination is very fast, this steady state level is reached quickly, but if elimination is very slow (in other words half-life [see this] is very long), a long time is needed to reach steady state. As a thumb rule, the body burden in a steady state is the daily dose multiplied by 1.5 times half-life (in days), e.g. in the case of PCDD/Fs, about 5000 daily doses.
A bathtub with a leaking bottom plug can illustrate this. If the leak is large, pouring water from a tap to the bathtub at a constant rate will raise the water level rapidly to such a relatively low height that as much pours out through the leak as is coming in from the tap. But if the leak is little, water level will rise longer and to a higher level, until the pressure will increase the output of water through the small leak to match the rate of the incoming water. Dioxins and PCBs leak out of the body very slowly, and therefore they keep cumulating even for decades until the elimination rate will finally be as great as the intake rate. The half-time of cumulation (the time during which 50% of steady state level will be reached) is the same as the half-life of elimination of the chemical. The half-life of TCDD is 7 to 8 years. This means that at a constant intake rate the body burden (the total amount of chemical in the body) will reach 50% of steady state in 7-8 years, 75 % in about 15 years and reach the steady state only in 40 to 50 years.
 
 

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