Baixe Food Safety Contaminants and Toxins - f ch7 e outras Notas de estudo em PDF para Engenharia de Alimentos, somente na Docsity! 7 Dioxins in Milk, Meat, Eggs and Fish H. Fiedler* United Nations Environment Programme, 11–13, Chemin des Anémones, CH-1219 Chatelaine, Geneva, Switzerland Introduction Contamination of food with chemicals plays an important role especially for persistent and bioaccumulating substances where dietary intake is the major pathway of exposure for humans. For the general population and some compounds, such as polychlorinated dibenzo-p-dioxins and polychlorinated dibenzofurans (PCDDs/ PCDFs), ingestion of food accounts for approximately 95% of the body burden. To guarantee safe and high quality food for human consumption, international regula- tion such as the Codex Alimentarius of the World Health Organization (WHO) and the Food and Agriculture Organization (FAO) has been established. This food code is followed in terms of harmonizing national food regulation, food additives, hygiene and processing as well as facilitating international trade (Codex Alimentarius, n.d.). The occurrence of unintentional contami- nation with chemicals but also with bacteria and viruses needs special attention and sur- veillance to protect humans from consuming unsafe food. Within the chemical contami- nants, a major concern is associated with dioxins and furans for several reasons: some of the PCDD/PCDF congeners are highly toxic, they are persistent and bioaccumulate in the food chain and thus can cause chronic effects due to long-term low exposure and, finally, dioxins and furans have been associ- ated with accidents and severe food contaminations. Nature of the Compounds Dioxins (PCDDs) and furans (PCDFs) are two groups of planar, tricyclic ethers which have up to eight chlorine atoms attached at carbon atoms 1–4 and 6–9. In total, there are 75 possi- ble PCDD congeners and 135 possible PCDF congeners, giving a total of 210 congeners (see Chapter 6). PCDDs and PCDFs are gen- erally very insoluble in water, are lipophilic and are persistent. Dioxins and furans have never been produced intentionally but are unwanted by-products of many chemical industrial processes and of all combustion processes. The sources and activities that lead to the formation of PCDDs/PCDFs, and sub- sequently to the release of these contaminants into air and water, with products and resi- dues, have been subject to intensive research, and today the most important dioxin sources seem to be identified. In the past, the chemical industry, with its production of organochlorine chemicals, was the major ©CAB International 2003. Food Safety: Contaminants and Toxins (ed. J.P.F. D’Mello) 153 20-Feb-03 7 * E-mail: hfiedler@unep.ch 169 Z:\Customer\CABI\A4382 - d’Mello\A4491 - d’Mello #D.vp Thursday, February 20, 2003 3:25:08 PM Color profile: Disabled Composite Default screen source of PCDDs/PCDFs: chemicals with high concentrations of dioxins and furans were pentachlorophenol (PCP), 2,4,5- trichloroacetic acid (2,4,5-T), polychlorinated biphenyls (PCBs; note that they contain PCDFs only, not PCDDs) (Fiedler et al., 1990). In 1977, PCDDs/PCDFs were identified in the emissions of a municipal waste incinera- tor in Amsterdam (Olie et al., 1977) and in 1980 the trace chemistry of fire was estab- lished, which states that, in thermal processes and in the presence of organic carbon, oxygen and chlorine, dioxins and furans can be formed (Bumb et al., 1980). Today, in industri- alized countries, the major sources of dioxin and furan release are combustion processes. Among these sources are the incineration of municipal and hospital waste, the production of iron and steel and other non-ferrous metals, e.g. copper, aluminium, lead and zinc (especially in recycling processes), and all types of uncontrolled burning, e.g. landfill fires, trash burning on soil, forest and bush fires (especially when chlorinated herbicides have been applied). Lastly, natural formation of PCDDs/ PCDFs has been shown on different occasions. Peroxidases are capable of synthesizing PCDDs/PCDFs from precursors such as chlorophenols. The formation of especially. Cl7DD and Cl8DD during the composting pro- cess has been proven where it was found that the international toxic equivalent (I-TEQ) increases by about 1–2 parts per trillion (ppt) during the composting process. Recent stud- ies provide a strong indication that PCDDs/ PCDFs may have been present in the environ- ment for considerably longer than the onset of the chlorine industry, and that they may be formed through non-anthropogenic activities. High concentrations of mainly PCDDs were found in mined ball clay from the USA, kaolinitic clay from Germany, deep soil samples from Great Britain, in dated marine sediment cores from Queensland/Australia and in man-made lake sediment cores from Mississippi, USA. Typical for all samples is the almost total absence of PCDFs and the nearly identical congener/isomer distribu- tion throughout all geographies. Almost all possible 210 congeners are released from anthropogenic sources and, due to chemical, physical and biological stability and long-range transport, are ubiquitous and have been detected in all environmental compartments. Due to the per- sistence of the 2,3,7,8-substituted congeners and the lipophilicity of these compounds, PCDDs/PCDFs accumulate in fatty tissues and in carbon-rich matrices such as soils and sediments. National release inventories With this mandate to facilitate a convention on reduction and elimination of releases of persistent organic pollutants (POPs), UNEP Chemicals will ‘. . . assist countries in the identification of national sources of dioxin/ furan releases by promoting access to the information on available sources of dioxins/ furans . . .’. Table 7.1 summarizes initial findings obtained from national inventories of releases of dioxins and furans, which have been compiled by the United Nations Environment Programme (UNEP) in 1999 and have been updated since then. The updated UNEP report for a reference year around 1995 would estimate annual releases to air of approximately 13,000 g I-TEQ year−1 from about 20 countries. This amount is based on best estimates from most countries and the lower bound emission for the rest of the countries. The upper estimate would be around 30,000 g I-TEQ year−1 and would also include another 2400 g I-TEQ in preliminary estimates from US sources, which have been addressed only recently (US-EPA, 2000a). The PCDD/PCDF releases into air per year and country are shown in Table 7.1. It should also be noted that, for example, Japan updates its inventory on an annual basis and for its last reporting year estimated much lower emissions, namely 2260–2440 g TEQ year−1 for 1999 coming down from 6301–6370 g TEQ year−1 in 1997 (Environ- ment Agency Japan, 2000). Most data are available for industrial- ized countries from Western Europe and North America. From Asia, there is only an inventory for Japan and an additional esti- mate of 22 g I-TEQ year−1 for emissions from 20-Feb-03 7 154 H. Fiedler 170 Z:\Customer\CABI\A4382 - d’Mello\A4491 - d’Mello #D.vp Thursday, February 20, 2003 3:25:08 PM Color profile: Disabled Composite Default screen for PCDDs/PCDFs, and concentrations of several hundred pg TEQ g−1 fat have been detected. These concentrations are much higher than those found in terrestrial animals, such as cattle, pigs or chickens. Top- predators, such as sea eagles or guillemots, also showed high concentrations of PCDDs/ PCDFs: as an example, 830–66,000 pg TEQ g−1 fat were found in Finnish white-tailed sea eagles (Buckley-Golder et al., 1999, Task 2). Understanding of the environmental fate of PCDDs/PCDFs is fundamental to eval- uating human exposure. Although the TEQ approach was developed and proven as a helpful tool for risk assessment, input data for models and exposure assessment have to be congener specific. Knowledge of the numerical values of certain parameters characterizing the proper- ties of individual PCDDs/PCDFs is necessary in order to predict the behaviour of the mix- tures found in the environment. The physical and chemical properties, which are measures of or control the behaviour of dioxins are: • their low vapour pressure (ranging from 4.0 × 10−8 mmHg for 2,3,7,8-Cl4DF to 8.2 × 10−13 mmHg for Cl8DD); • their extremely low solubility in water (ranging from 419 ng l−1 for 2,3,7,8-Cl4DF, 7.9 and 19.3 ng l−1 for 2,3,7,8-Cl4DD to 0.074 ng l−1); • their solubility in organic/fatty matrices (log Kow range from 5.6 for Cl4DF and 6.1/7.1 for Cl4DD to 8.2 for Cl8DD); • their preference for binding to organic matter in soil and sediments (log Koc values for 2,3,7,8-Cl4DD were between 6.4 and 7.6). The processes by which PCDDs/PCDFs move through the environment are reason- ably well known. PCDDs/PCDFs are multi- media pollutants and, once released to the environment, become distributed between environmental compartments (Buckley- Golder et al., 1999, Task 3). PCDDs/PCDDFs are semi-volatile com- pounds and, in the atmosphere, can exist in both the gaseous phase and bound to particles, depending upon the congener and the environmental conditions. Especially during the warmer (in the northern hemisphere, summer) months, the lower chlorinated PCDD/PCDF congeners tend to be found predominantly in the vapour phase. PCDD/PCDF in the vapour phase can undergo photochemical transformation, with a dechlorination process leading to more toxic congeners if octa- and heptachlorinated con- geners degrade to tetra- and pentachlorinated and finally to non-toxic compounds with only three or fewer chlorine atoms. PCDDs/PCDFs attached to particulate matter seem to be resistant to degradation. In the terrestrial food chain (air → grass → cattle → milk/meat → man), PCDDs/ PCDFs can be deposited on plant surfaces via wet deposition, via dry deposition of chemi- cals bound to atmospheric particles or via diffusive transport of gaseous chemicals in the air to the plant surfaces. Each of these processes is governed by a different set of plant properties, environmental parameters and atmospheric concentrations. Investiga- tions with native grassland cultures showed that dry gaseous deposition played the domi- nant role for the accumulation of the lower chlorinated PCDDs/PCDFs, whereas dry par- ticle-bound deposition played an important role in the uptake of the PCDDs/PCDFs with six and more chlorine atoms. There was also some evidence indicating an input of the higher chlorinated PCDD/PCDF from wet deposition (Welsch-Pausch et al., 1995). Levels in, for example, grass reflect recent exposure to PCDDs/PCDFs, as vegetation is only exposed for a relatively short time, with new growth replacing old and crops being harvested. For agricultural leaf crops, the main source of contamination is direct deposition from the atmosphere and soil splash. Root uptake and translocation of dioxin contamination into the crop has been confirmed for courgette and cucumber only. Grazing animals are exposed to dioxins by ingesting contaminated pasture crops, and PCDDs/PCDFs are found to accumulate primarily in the fatty tissues and milk. For agricultural soils, an additional source of PCDD/PCDF can be the application of sewage sludge. Small amounts of PCDDs/ PCDFs deposited on to soil can be returned to the atmosphere by the resuspension of pre- viously deposited material or revolatilization Dioxins in Milk, Meat, Eggs and Fish 157 20-Feb-03 7 173 Z:\Customer\CABI\A4382 - d’Mello\A4491 - d’Mello #D.vp Thursday, February 20, 2003 3:25:09 PM Color profile: Disabled Composite Default screen of the less chlorinated congeners. Because of their chemical characteristics and very low solubility, PCDDs/PCDFs accumulate in most soil types, with very little water leaching and negligible degradation of the 2,3,7,8- substituted PCDD/PCDF congeners. PCDDs/PCDFs partition quickly to organic matter and so accumulate in sedi- ments. They accumulate in aquatic fauna as a result of the ingestion of contaminated organic matter. The concentration of PCDDs/ PCDFs in fish tissue is found to increase up the food web (biomagnification) as a result of the progressive ingestion of contaminated prey. Carry-over rates: from environment to food The transfer of dioxins from grass into cattle has been studied, and carry-over rates have been determined. In general, carry-over rates decrease with increasing degree of chlorina- tion of the chemical, indicating that absorp- tion through the gut also decreases. This decrease in absorption is attributed to the greater hydrophobicity of the higher chlori- nated PCDDs/PCDFs, which inhibits their transport across aqueous films in the diges- tive tract of the cow. In studies conducted at background concentrations, the highest transfer was deter- mined for two lower chlorinated dibenzo-p- dioxins and one dibenzofuran, namely 2,3,7,8- Cl4DD (2,3,7,8- tetrachlorodibenzo-p-dioxin), 1,2,3,7,8-Cl5DD (1,2,3,7,8-pentachlorodibenzo- p-dioxin), and 2,3,4,7,8-Cl5DF (2,3,4,7,8-penta- chlorodibenzofuran). For these three conge- ners about 30–40% are transferred from feed to cow’s milk. About 20% are transferred for the 2,3,7,8-substituted Cl6DD (hexachlorodi- benzo-p-dioxin) and Cl6DF (hexachlorodi- benzofuran) homologues. For the hepta- and octachlorinated PCDDs and PCDFs, not more than 4% of the ingested congeners find their way into the milk. Although highly depend- ent on the characteristics of each congener, the overall transfer on a TEQ basis is about 30%; in other words: about 30% of the most toxic PCDD/PCDF congeners which are ingested by the cow are excreted via the milk (Welsch-Pausch and McLachlan, 1998). Distribution in Foods The largest database on dioxin concentrations in food exists for some European countries, and the major findings are discussed in this following section. From North America, especially from the USA, the database on dioxin concentrations in food is small com- pared with the European database (US-EPA, 2000b). The Organochlorine Programme in New Zealand found very low concentra- tions of PCDDs/PCDFs in the foodstuffs (NZ, 1998). Concentrations of PCDD/PCDF ranged from 0.072 to 0.57 pg I-TEQ g−1 fat for meats and meat products; 0.056–0.26 pg I-TEQ g−1 fat for dairy products, 0.41–1.82 pg I-TEQ g−1 fat for fish, and 0.12 and 0.29 pg I-TEQ g−1 fat for eggs and poultry, respec- tively. Cereal products and bread were between 0.19 and 0.66 pg I-TEQ g−1 fat (all numbers include half of the detection limit for non-quantifiable congeners when calcu- lating the TEQ) In 2000, a database with information on concentrations of PCDDs, PCDFs and/or dioxin-like PCBs (polychlorinated biphenyls) in food products and human milk was estab- lished and evaluated. The samples originated from rural and industrial sites in ten EU Mem- ber States and were collected between 1982 and 1999. Due to the high demands on dioxin and furan analyses, broad field surveys based on a large number of samples are rare. Never- theless, the current database can be con- sidered relatively complete for PCDDs and PCDFs, but rather incomplete for dioxin-like PCBs. With respect to dioxin contamination, highest relevance is for foods of animal origin, where in principle only 2,3,7,8- substituted congeners are found. These are the most toxic and most persistent. Foods of plant origin normally have lower concentra- tions of dioxins and furans but, for example, grass plays an important role as feedstuff for cattle, sheep, etc., and the contamination in the grass translocates into the animal and its products, e.g. meat, milk. Humans and breast-fed infants are the last steps in the food chain and thus have the highest concentrations. 20-Feb-03 7 158 H. Fiedler 174 Z:\Customer\CABI\A4382 - d’Mello\A4491 - d’Mello #D.vp Thursday, February 20, 2003 3:25:09 PM Color profile: Disabled Composite Default screen A survey of European food data can be summarized as follows: • The national average concentration of PCDDs/PCDFs in eggs, fats, oils, meat (and its products) and milk (and its products) is generally less than 1 pg I-TEQ g−1 fat, with an upper limit of 2–3 pg I-TEQ g−1 fat. • PCDDs/PCDFs in fish ranged from 0.25 pg I-TEQ g−1 fresh weight (FW) up to 10–20 pg I-TEQ g−1 FW. • Concentrations in fruits, vegetables and cereals were generally close to the limits of quantification. • Concentrations in meat and meat pro- ducts and fish and fish products seem to vary with the organ analysed, e.g. higher concentrations on a fat basis in liver than in adipose tissue. Further, there is a difference between animal species, e.g. lower concentrations on a fat basis in pork than in beef, poultry or mutton. • Decreasing trends in the concentration of PCDDs and PCDFs in foods, especially in consumer milk and some types of meat, have been determined in a few countries. However, the available infor- mation is insufficient and too incomplete to draw a general conclusion on tempo- ral trends for other types of foods. • Although the data on concentrations of dioxin-like PCBs in foods are scarce, the available information indicates that these PCB congeners may add one to two times of the PCDD/PCDF TEQ. In particular, PCB congeners 126 and 118 may contribute much more strongly to the total TEQ content of foods than do the PCDDs and PCDFs. • The largest database exists for PCDDs and PCDFs in human milk, and for some countries strong downward trends have been observed. Since 1995, the national average concentrations have ranged between 8 and 16 pg I-TEQ g−1 fat. Although the database is incomplete, results from the years 1990–1994 indicate that, on a TEQ basis, PCBs can account for the same to up to three times the concentration of the PCDDs and PCDFs (7–29 pg TEQ g−1 fat). Milk and milk products Analysis of dioxins in cow’s milk has been performed since 1986. As dairy products are the main contributor to the human dioxin burden and cow’s milk also serves as a biomonitor, the database for milk samples is large. When comparing dioxin concentra- tions in cow’s milk, seasonal variations of up to 25% can occur due to changes in animal feeding stuffs. The differences between cer- tain regions can be even higher. In the late 1980s, contamination of cow’s milk with dioxins by chlorine-bleached cardboard con- tainers was established. After elimination of elemental chlorine in the bleaching process, the PCDD/PCDF levels in cow’s milk were no longer influenced by cardboard contain- ers. At the end of 1997, increasing levels of dioxins in cow’s milk were detected in Baden-Württemberg (Germany). Finally, contaminated citrus pulp, a component of feedingstuff imported from Brazil, was found to be the cause of elevated dioxin concentrations (Malisch, 1998a,b). This contamination was found in other federal Länder of Germany and later other European countries as well. The most recent surveys show national average concentrations in the range of 0.3–2.1 pg I-TEQ g−1 for PCDDs/PCDFs and 0.2–1.8 pg PCB TEQ g−1 fat for dioxin-like PCBs. To explain the concentrations of PCDDs/PCDFs/PCBs in milk and milk prod- ucts, several factors have to be considered: obviously, deposition of dioxins and related compounds emitted from either point or diffuse sources on pasture as well as con- taminations present in animal feedstuffs are important routes of exposure for cattle. Due to stringent enforcement of limit values, the national average concentrations of dioxins in dairy products have decreased over the last decade in many European countries. Meat and meat products PCDD/PCDF concentrations in foodstuffs of animal origin depend on the animal. Thus, distinctions have to be made between Dioxins in Milk, Meat, Eggs and Fish 159 20-Feb-03 7 175 Z:\Customer\CABI\A4382 - d’Mello\A4491 - d’Mello #D.vp Thursday, February 20, 2003 3:25:10 PM Color profile: Disabled Composite Default screen for which data were available. The total intake of I-TEQ differed from country to country. Reasons for these differences may result from different food consumption habits but also from applied sampling strategy and the large variations in concentrations of dioxin-related substances in some of the food groups (e.g. vegetables and fruits, eggs and fish). It is well known that during the breast-feeding period, on a body weight basis, the intake of PCDDs and PCDFs is 1–2 orders of magnitude higher than the average adult intake. A few countries (i.e. Finland, Ger- many, The Netherlands, Sweden and the UK) reported clear downward trends for the exposure of the general population to dioxins and furans and, for Germany (see Table 7.4), Finland, The Netherlands and Sweden, this decline is also noted for concentrations in human milk. Although different dietary habits make direct comparison of results from different countries difficult, the daily intakes of PCDDs and PCDFs by males living in New Zealand are consistently lower than those of other countries. The intakes are also below the WHO-recommended tolerable daily intake (TDI) of 1–4 pg TEQ kg−1 BW day−1. The dietary intake estimated for an 80 kg adult male consuming a median energy (10.8 MJ day−1) diet was 14.5 pg I-TEQ day−1 (equiva- lent to 0.18 pg I-TEQ kg−1 BW day−1) and an additional 12.2 pg TEQ day−1 (= 0.15 pg TEQ kg−1 BW day−1) for dioxin-like PCBs. Dietary intakes estimated for a 70 kg adolescent male consuming a high energy (21.5 MJ day−1) diet were 30.6 pg I-TEQ day−1 (= 0.44 pg I-TEQ kg−1 BW day−1) and 22.7 pg PCB-TEQ day−1 (= 0.32 pg TEQ kg−1 BW day−1) (NZ, 1998). Food and feedingstuff-related accidents In the past, high exposures occurred through accidents. Well-known examples are the con- tamination of edible rice oils, such as the Yusho in Japan in 1968 and the Yu-Cheng in Taiwan in 1978. In these cases, PCBs from hydraulic oils leaked into edible oils, which were sold and consumed by thousands of people. Severe toxic effects were detected in both populations due to high levels of PCDFs and PCBs (Needham, 1993; Guo et al., 1994; Masuda, 1994). Each year from 1997 to 1999, cases of dioxin (and PCB) contamination of animal feeds and foods occurred. Among these are the dioxin contamination of citrus pulp pellets (an ingredient for feeding stuffs) from Brazil in the years 1997–1998, the contamination of animal feeds with PCBs and dioxins in Belgium in spring of 1999, and the dioxin con- tamination of kaolinitic clay (a feed additive) from some mines in the USA and Germany. In each of these cases, preventive measures were taken to avoid a further distribution of contaminated products and to protect the consumer against foods with elevated levels. 11-Mar-03 7 162 H. Fiedler Age (months) Year Mean intake (pg TEQ day−1) Mean intake (pg TEQ BW day−1) Comments 1 2 3 4 6 5 6 7–9 4 4 4 4 1998 1998 1998 1998 1998 1998 1998 1998 1986–1990 1992 1994 1996 291 338 360 370 369 271 180 108 879 604 502 402 70 68 62 57 48 38 24 13 135 93 77 62 Fully breast-fed Fully breast-fed Fully breast-fed Fully breast-fed Fully breast-fed Partly breast-fed Partly breast-fed Partly breast-fed Fully breast-fed Fully breast-fed Fully breast-fed Fully breast-fed Table 7.4. Dietary intake of PCDDs/PCDFs of breast-fed infants in Germany. 178 Z:\Customer\CABI\A4382 - d’Mello\A4491 - d’Mello #G.vp 11 March 2003 12:21:41 Color profile: Disabled Composite Default screen The citrus pulp pellet contamination From mid-1997 until March 1998, on average, twice the concentrations of PCDDs/PCDFs in cow’s milk were detected by German Food Control laboratories: starting from a level of about 0.6 pg I-TEQ g−1 fat in summer 1997, the average concentration increased to 1.41 pg I-TEQ g−1 fat in different regions of Germany in February 1998. The highest value was 7.86 pg I-TEQ g−1 fat and thus exceeded the concentration of 5 pg I-TEQ g−1 fat, the maximum permissible concentration to place milk products on the German market. Although this observation was made in Germany first, later the same observation was found in the 12 Member States of the EU. Whereas feedingstuff samples typically had concentrations in the range from 100 to 300 pg I-TEQ kg−1, a compound feed for milk production, which had been found at two different dairy farms, had about 1800 pg I-TEQ kg−1. It affected the level of dioxins and furans in cow’s milk, beef and veal (Malisch, 1998a,b). The contamination was traced back to citrus pulp pellets imported from Brazil and used in compound feed for ruminants all over Europe. The Brazilian citrus pellet production had been contaminated by dioxin-containing lime, which was a by-product from a chemical factory. The lime apparently was used for feed production against the advice of the supplier, who believed it was for construction. As men- tioned earlier, this contamination may have had an impact on the general level of dioxin exposure of the European population and a slight increase in the dioxin content in breast milk and tissue. The Belgian chicken accident In March 1999, serious animal health prob- lems in poultry production were discovered in Belgium. There was a marked reduction in egg hatchability and an increased mortality of chickens. At the end of May, analysis of feedingstuff samples, hens and breeding eggs showed high levels of dioxins and furans. The first analyses showed dioxin concentrations 1000 times above background level; the contamination dropped by more than 100 times from February to March 1999 (Table 7.5). The contamination seems to have been caused by the discharge of about 25 l of PCB transformer oil into a waste collection unit for animal fats recycled into animals feed contaminating 107 t of fat. From this, about 90 t of fat was used for production of feedstuff for poultry, and the remaining fat was used for production of milk and meat. At the beginning of October 1999, the number of affected or suspected farms was 505 poultry farms, 1625 pig farms and 411 cattle farms. The estimated costs for Belgium in con- nection with the dioxin food contamination is about US$1 billion; indirect costs are estimated to be three times higher. A correct waste disposal of the 25 l of transformer oil would have cost about US$1000. Though the Belgian dioxin contamination had a major effect on the Belgian food production econ- omy, it gave only a short-term peak exposure to dioxins and furans for humans, which cannot be detected in the general population. The kaolinitic (ball) clay case In 1999, a dioxin contamination of poultry and mink was traced back to the use of kaolinitic clay as an anti-caking agent in poultry feed and in mineral feed for mink. The origin of the contamination was traced back to a ball clay mine in Germany. Similar examples were found in the USA, where catfish and beef had been impacted through the use of ball clay in animal feedingstuff production. The Brandenburg case Repeated detection of elevated dioxin levels in eggs produced in the German state of Brandenburg was identified in 1999 when, in an open system, grass meal (for feedingstuff Dioxins in Milk, Meat, Eggs and Fish 163 20-Feb-03 7 Concentration (pg WHO-TEQ kg−1) Poultry feed Poultry fat Egg fat 811,000 775 266 1,009 713 Table 7.5. Belgian dioxin accident – PCDD/ PCDF concentrations in feedingstuff and food. 179 Z:\Customer\CABI\A4382 - d’Mello\A4491 - d’Mello #D.vp Thursday, February 20, 2003 3:25:11 PM Color profile: Disabled Composite Default screen production) was dried by burning wood as the fuel. All types of wood were burned, including waste wood with chemical contam- ination from former painting or use of wood preservatives. The choline chloride case In the year 2000, a dioxin contamination in choline chloride pre-mixtures for feed- stuff was detected in Germany. The original choline chloride (= vitamin K) from a Belgian producer was not contaminated but the Spanish feedstuff pre-mix producer who sold the pre-mix to Germany had added pine sawdust to the product as a carrier. This pine sawdust was heavily contaminated with dioxin-containing pentachlorophenol. Uptake and Human Exposure, Maternal Transmission For humans (and animals), the major uptake of dioxins and furans is via ingestion. The 2,3,7,8-substituted congeners have long half- lives, generally of the order of years, and this causes these compounds to bioaccumulate. Metabolism is almost negligible and, to calcu- late body burdens, intake is the parameter for countermeasures. Protection of the fetus is of particular concern when precautionary actions are to be taken. For the general population, the major pathway of exposure to PCDDs, PCDFs and PCBs is through food. More than 90% of human exposure occurs via the diet, with foods of animal origin usually being the pre- dominant sources. Contamination of food is caused primarily by deposition of emissions from combustion sources such as waste incineration, the metal industry, energy production or household heating, and subse- quent accumulation in the food chain. Due to their lipophilicity, PCDDs, PCDFs and PCBs are associated with fat. Contamination of food may also occur through contaminated feed, improper application of sewage sludge, flood- ing of pastures, waste effluents and certain types of food processing or packaging (SCF, 2000). Some subpopulations may have higher exposure to dioxins, furans and PCBs as a result of particular consumption habits, e.g. nursing infants and subsistence fishermen living close to contaminated waters. Toxicity and Clinical Effects Toxic effects in laboratory animals The extraordinary potency of 2,3,7,8-TCDD (tetrachlorodibenzo-p-dioxin) and related 2,3,7,8-substituted PCDDs and PCDFs has been demonstrated in many animal species. They elicit a broad spectrum of responses in experimental animals such as: liver damage (hepatoxicity); suppression of the immune system (immunotoxicity); formation and development of cancers (carcinogenesis); abnormalities in fetal development (teratoge- nicity); developmental and reproductive tox- icity; skin defects (dermal toxicity); diverse effects on hormones and growth factors; and induction of metabolizing enzyme activities (which increases the risk of metabolizing precursor chemicals to produce others which are more biologically active). It is generally believed that 2,3,7,8- substituted PCDDs and PCDFs exhibit the same pattern of toxicity. The toxic responses are initiated at the cellular level, by the bind- ing of PCDDs/PCDFs to a specific protein in the cytoplasm of the body cells, the aryl hydrocarbon receptor (AhR). The 2,3,7,8- substituted PCDDs/PCDFs bind to the AhR and induce CYP1A1 (cytochrome P450 1A1) and CYP1A2 (cytochrome P450 1A2) gene expression. The binding to the AhR consti- tutes a first and necessary step to initiate the toxic and biochemical effects of dioxins, although it is not sufficient alone to explain the full toxic effects. This mechanism of action of 2,3,7,8- Cl4DD parallels in many ways that of the steroid hormones, which have a broad spectrum of effects throughout the body and where the effects are caused primarily by the parent compound. However, TCDDs and steroid hormone receptors (e.g. oestrogen, androgen, glucocorticoid, thyroid hormone, vitamin D3 and retinoic acid receptors) do 20-Feb-03 7 164 H. Fiedler 180 Z:\Customer\CABI\A4382 - d’Mello\A4491 - d’Mello #D.vp Thursday, February 20, 2003 3:25:11 PM Color profile: Disabled Composite Default screen of workers with severe chloracne in the BASF accident cohort in Germany, and up to 2252 kg−1 in the Boehringer cohort in Germany. These calculated blood 2,3,7,8- TCDD levels in workers at time of exposure were in the same range as the estimated blood levels in a 2-year rat carcinogenicity study. In rats exposed to 100 ng kg−1 BW 2,3,7,8- TCDD day−1, hepatocellular carcinomas and squamous cell carcinomas of the lung were observed. Estimated blood levels were 5000–10,000 ng kg−1 2,3,7,8-TCDD. In the same study, in rats exposed to 10 ng kg−1 BW 2,3,7,8-TCDD day−1, hepatocellular nodules and focal alveolar hyperplasia were observed. Estimated blood levels were 1500–2000 ng kg−1 2,3,7,8-TCDD. These results indicate par- allel tumorigenic responses to high exposure to 2,3,7,8-TCDD in both humans and rats. In view of the results mentioned above, it should be noted that the present background levels of 2,3,7,8-TCDD in human populations (2–3 ng kg−1) are 100–1000 times lower than those observed in this rat carcinogenicity study. Evaluation of the relationship between the magnitude of the exposure in experimen- tal systems and the magnitude of the response (i.e. dose–response relationships) does not permit conclusions to be drawn on the human health risks from background exposures to 2,3,7,8-TCDD (IARC, 1997). A Working Group for IARC (Interna- tional Agency for Research on Cancer, Lyon, France) classified 2,3,7,8-TCDD as being carcinogenic to humans (IARC, 1997). In making this overall evaluation, the working group took into consideration the following supporting evidence: 1. 2,3,7,8-TCDD is a multisite carcinogen in experimental animals that has been shown by several lines of evidence to act through a mechanism involving the AhR. 2. This receptor is highly conserved in an evolutionary sense and functions the same way in humans as in experimental animals. 3. Tissue concentrations are similar both in heavily exposed human populations in which an increased overall cancer risk was observed and in rats exposed to carcinogenic dosage regimens in bioassays. Other PCDDs and non-chlorinated dibenzo-p-dioxin are not classifiable as to their carcinogenicity in humans. The IARC concluded that there is inade- quate evidence in humans for the carcinoge- nicity of PCDFs. There is inadequate evidence in experimental animals for the carcinogeni- city of 2,3,7,8-Cl4DF. There is limited evidence in experimental animals for the carcinogeni- city of 2,3,4,7,8-Cl5DF and 1,2,3,4,7,8-Cl6DF. The overall evaluation states that PCDFs are not classifiable as to their carcinogenicity in humans (group 3). In its recent dioxin reassessment, the US-EPA basically follows the IARC classifica- tions (US-EPA, 2000c) and concludes that ‘un- der EPA’s current approach, TCDD is best characterized as a “human carcinogen”’. This means that, based on the weight of all of the evidence (human, animal, mode of action), TCDD meets the stringent criteria that allow EPA and the scientific community to accept a causal relationship between TCDD exposure and cancer hazard. The guidance suggests that ‘human carcinogen’ is an appropriate descriptor of carcinogenic potential when there is an absence of conclusive epidemiolog- ical evidence to clearly establish a cause and effect relationship between human exposure and cancer, but there are compelling carcino- genicity data in animals and mechanistic information in animals and humans demon- strating similar modes of carcinogenic action. The ‘human carcinogen’ descriptor is sug- gested for TCDD because all of the following conditions are met. Occupational epidemio- logical studies show an association between TCDD exposure and increases in cancer at all sites, in lung cancer, and perhaps at other sites, but the data are insufficient on their own to demonstrate a causal association. There is extensive carcinogenicity in both sexes of multiple species of animals at multiple sites (IARC, 1997). Risk Assessment First risk assessments only focused on the most toxic congener, 2,3,7,8-TCDD. Soon it Dioxins in Milk, Meat, Eggs and Fish 167 20-Feb-03 7 183 Z:\Customer\CABI\A4382 - d’Mello\A4491 - d’Mello #D.vp Thursday, February 20, 2003 3:25:11 PM Color profile: Disabled Composite Default screen was recognized, though, that all PCDDs/ PCDFs substituted at least in positions 2, 3, 7 or 8 are highly toxic and thus major contri- butors to the overall toxicity of the dioxin mixture. In addition, despite the complex composition of many PCDD/PCDF- containing ‘sources’, only congeners with substitutions in the lateral positions of the aromatic ring, namely the carbon atoms 2, 3, 7 and 8, persist in the environment and accumulate in food chains. For regulatory purposes so-called toxic- ity equivalency factors (TEFs) have been developed for risk assessment of complex mixtures of PCDDs/PCDFs (NATO/CCMS, 1988). The TEFs are based on acute toxicity values from in vivo and in vitro studies. This approach is based on the evidence that there is a common, receptor-mediated mechanism of action for these compounds. Although the scientific basis cannot be considered as solid, the TEF approach has been adopted as an administrative tool by many agencies and allows conversion of quantitative analytical data for individual PCDD/PCDF congeners into a single TEQ. As TEFs are interim values and administrative tools, they are based on the present state of knowledge and should be revised as new data become available. Today’s most commonly applied TEFs were established by a NATO/CCMS Working Group on Dioxins and Related Compounds as international toxicity equivalency factors (I-TEFs) (NATO/CCMS, 1988). However, in 1997, a WHO/IPCS (World Health Organ- ization/Intergovernmental Programme on Chemical Safety) working group re-evaluated the I-TEFs and established a scheme, which besides human and mammalian TEFs, also established TEFs for birds and fish (Table 7.6). The same expert group also assessed the dioxin-like toxicity of PCB and assigned TEF values for 12 co-planar and mono-ortho- substituted PCB congeners (see Table 7.7) (WHO, 1997). It should be noted that most existing legislation and most assessments still use the I-TEF scheme. However, the recently agreed Stockholm Convention on POPs (for reference see UNEP, 2001) refers to the com- bined WHO-TEFs as the starting point as a reference. Different international expert groups have performed health risk assessment of 11-Mar-03 7 168 H. Fiedler WHO-TEF Congener I-TEF Humans/mammals Fish Birds 2,3,7,8-Cl4DD 1,2,3,7,8-Cl5DD 1,2,3,4,7,8-Cl6DD 1,2,3,7,8,9-Cl6DD 1,2,3,6,7,8-Cl6DD 1,2,3,4,6,7,8-Cl7DD Cl8DD 2,3,7,8-Cl4DF 1,2,3,7,8-Cl5DF 2,3,4,7,8-Cl5DF 1,2,3,4,7,8-Cl6DF 1,2,3,7,8,9-Cl6DF 1,2,3,6,7,8-Cl6DF 2,3,4,6,7,8-Cl6DF 1,2,3,4,6,7,8-Cl7DF 1,2,3,4,7,8,9-Cl7DF Cl8DF 1 0.5 0.1 0.1 0.1 0.01 0.001 0.1 0.05 0.5 0.1 0.1 0.1 0.1 0.01 0.01 0.001 1 1 0.1 0.1 0.1 0.01 0.0001 0.1 0.05 0.5 0.1 0.1 0.1 0.1 0.01 0.01 0.0001 1 1 0.5 0.01 0.01 0.001 — 0.05 0.05 0.5 0.1 0.1 0.1 0.1 0.01 0.01 0.0001 1 1 0.05 0.01 0.1 < 0.001 — 1 0.1 1 0.1 0.1 0.1 0.1 0.01 0.01 0.0001 For all non-2,3,7,8-substituted congeners, no TEF has been assigned. Table 7.6. International toxicity equivalency factors (I-TEFs) for PCDDs/PCDFs (NATO/CCMS, 1988) and WHO-TEFs for PCDDs/PCDFs (WHO, 1997). 184 Z:\Customer\CABI\A4382 - d’Mello\A4491 - d’Mello #G.vp 11 March 2003 12:22:04 Color profile: Disabled Composite Default screen dioxins and related compounds. A Nordic expert group (for Scandinavian countries) proposed a TDI for 2,3,7,8-TCDD and struc- turally similar chlorinated PCDDs and PCDFs of 5 pg kg−1 BW, based on experimental studies on cancer, reproduction and immunotoxicity. A first WHO meeting in 1990 established a TDI of 10 pg kg−1 BW for 2,3,7,8- TCDD, based on liver toxicity, reproductive effects and immunotoxicity, and making use of kinetic data in humans and experimental animals. Since then, new epidemiological and toxicological data have emerged, in particular with respect to neurodevelopmental and endocrinological effects. In May 1998, a joint WHO–European Centre for Environment and Health (ECEH) and IPCS expert group re-evaluated the old TDI and came up with a new TDI (which is a range) of 1–4 pg TEQ kg−1 BW, which includes all 2,3,7,8-substituted PCDDs and PCDFs as well as dioxin-like PCBs (for reference, see the 12 PCBs in Table 7.7). The TDI is based on the most sensitive adverse effects, especially hormonal, reproductive and developmental effects, which occur at low doses in animal studies, e.g. in rats and monkeys at body burdens in the range of 10–50 ng kg−1 BW. Human daily intakes corre- sponding to body burdens similar to those associated with adverse effects in animals were estimated to be in the range of 10–40 pg kg−1 BW day−1. The 1998 WHO-TDI does not apply an uncertainty factor to account for interspecies differences in toxicokinetics since body burdens have been used to scale doses across species. However, the estimated human intake was based on lowest observed adverse effect levels (LOAELs) and not on no observed adverse effect levels (NOAELs). For many end points, humans might be less sensi- tive than animals; uncertainty still remains regarding animal to human extrapolations. Further, differences between animals and humans exist in the half-lives for the different PCDD/PCDF congeners. To account for all these uncertainties, a composite uncertainty factor of 10 was recommended. As subtle effects might already be occurring in the general population in developed countries at current background levels of exposure to dioxins and related compounds, the WHO expert group recommended that every effort should be made to reduce exposure to below 1 pg TEQ kg−1 BW day−1 (WHO, 1998). In November 2000, the Scientific Com- mittee on Food (SCF) for the European Com- mission recommended a temporary tolerable weekly intake (t-TWI) of 7 pg 2,3,7,8-TCDD kg−1 BW using the body weight approach. It was also concluded that the TEQ approach should be applied to include all 2,3,7,8- substituted PCDDs/PCDFs and dioxin-like PCBs. Thus, the t-TWI of 7 pg TEQ kg−1 BW day−1 is applicable for these compounds (seven PCDDs, ten PCDFs and 12 PCBs). The t-TWI is based on the most sensitive end points from animal studies, e.g. develop- mental and reproductive effects in rats and monkeys and endometriosis in monkeys (SCF, 2000). Dioxins in Milk, Meat, Eggs and Fish 169 20-Feb-03 7 Congener Humans/mammals Fish Birds 3,4,4´,5-TCB (81) 3,3´,4,4´-TCB (77) 3,3´,4,4´,5-PeCB (126) 3,3´,4,4´,5,5´-HxCB (169) 2,3,3´,4,4´-PeCB (105) 2,3,4,4´,5-PeCB (114) 2,3´,4,4´,5-PeCB (118) 2´,3,4,4´,5-PeCB (123) 2,3,3´,4,4´,5-HxCB (156) 2,3,3´,4,4´,5´-HxCB (157) 2,3´,4,4´,5,5´-HxCB (167) 2,3,3´,4,4´,5,5´-HpCB (189) 0.0001 0.0001 0.1 0.01 0.0001 0.0005 0.0001 0.0001 0.0005 0.0005 0.00001 0.0001 0.0005 0.0001 0.005 0.00005 < 0.000005 < 0.000005 < 0.000005 < 0.000005 < 0.000005 < 0.000005 < 0.000005 < 0.000005 0.1 0.05 0.1 0.001 0.0001 0.0001 0.00001 0.00001 0.0001 0.0001 0.00001 0.00001 Table 7.7. TEFs for PCBs (WHO, 1997). 185 Z:\Customer\CABI\A4382 - d’Mello\A4491 - d’Mello #D.vp Thursday, February 20, 2003 3:25:12 PM Color profile: Disabled Composite Default screen 20-Feb-03 7 172 H. Fiedler Foodstuffs of animal origin Country PCDDs and PCDFs PCBs Austria Belgium Denmark Finland France Germany Greece Ireland Italy Luxemburg Norway Portugal Spain Sweden The Netherlands UK Provisional limits WHO-TEQ (PCDD/PCDF) g−1 fat: pork 2, milk 3, poultry and eggs 5 and beef 6 pg Milk, bovine, poultry, animal fats and oils, eggs and derived products, if > 2% fat: 5 pg WHO-TEQ (PCDD/PCDF) g−1 fat Pork and derived products, if > 2% fat: 3 pg WHO-TEQ (PCDD/PCDF) g−1 fat No national limits No national limits Milk and dairy products: 5 pg g−1 fat Recommendations for milk and dairy products in pg I-TEQ g−1 milk fat: • < 0.9 (desirable target) • 3.0 (identification of sources; measures to reduce input; recommendations for land use; recommendation to stop direct supply of milk products to consumers) • > 5.0 (ban on trade of contaminated milk products) No national limits International norms No national limits Recommended: pork 2, beef 6, poultry 5, milk 3 and eggs 5 pg g−1 fat No national limits No national limits Levels > 5 pg g−1 fat are considered as non-acceptable in dairy products No national limits Dairy products and foods with milk or dairy product as ingredients: 6 pg TEQ g−1 fat Guideline for cows’ milk: 0.66 ng WHO-TEQ kg−1 whole milk (16.6 ng WHO-TEQ kg−1 fat) For the sum of PCBs 28, 52, 101, 118, 138, 153 and 180 Milk and derived products, if > 2% fat: 100 ng g−1 fat Bovine, pork, poultry, animal fats and oils, eggs and derived products, if > 2% fat: 200 ng g−1 fat No national limits No national limits No national limits Congener-specific limits for PCBs 28, 52, 101, 138, 153 and 180 in foods of animal origin: 0.008–0.6 mg kg−1 fat or whole weight basis No national limits International norms Action level for the sum of tri- to octachlorobiphenyls in various foods of animal origin (excluding freshwater and marine fish and derived products): 100 ng g−1 fat No national limits No national limits No national limits PCB 153: meat products > 10% fat: 0.1, milk and milk products > 2% fat: 0.02, and eggs: 0.1 mg kg−1 fat Meat products < 10% fat: 0.01, milk and milk products < 2% fat: 0.001, and fish: 0.1 mg kg−1 wet weight Congener-specific limits for PCBs 28, 52, 101, 118, 138, 153 and 180 in foods of animal origin: 0.02–2 mg kg−1 fat (for fish mg kg−1 wet weight) Table 7.9. 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