Toxicity PCDDs and PCDFs

C-rings of the benzofuran system. Most of these isomers had all their lateral positions chlorinated. Contrary, all the PCDF isomers apparently excreted had two vicinal hydrogenated C-atoms in at least one of the two rings, and these unblocked positions are involved in the metabolism by forming epoxides, see Figure 3 (23) The data discussed here show a striking similarity between the most toxic PCDD and PCDF isomers and the isomers most efficiently retained. 

Figure 2. The most toxic PCDD and PCDF isomers...

Rappe (25) summarized all the literature with regard to the analysis of polychlorinated dioxins and furans and concluded that, with the standards now available, isomer-specific analyses can be performed for all toxic PCDD and PCDF isomers. However, some attention still has to be focused on characteristics of analytical and concentration techniques that can be promising for the future (26). 

Polychlorinated diphenyl ethers (PCDE) are common impurities in chlorophenol formulations, which were earlier used as fungicides, slimicides, and as wood preservatives. PCDEs are structurally and by physical properties similar to polychlorinated biphenyls (PCB). They have low water solubility and are lipophilic. PCDEs are quite resistant to degradation and are persistent in the environment. In the aquatic environment, PCDEs bioaccumulate. These compounds are found in sediment, mussel, fish, bird, and seal. PCDEs show biomagnification potential, since levels of PCDEs increase in species at higher trophic levels. PCDEs are also detected in human tissue. Despite the persistence and bio accumulation, the significance of PCDEs as environmental contaminants is uncertain. The acute toxicity and Ah-receptor-me-diated (aryl hydrocarbon) activity of PCDEs is low compared to those of polychlorinated di-benzo-p-dioxins (PCDD) and dibenzofurans (PCDF). Due to structural similarity to thyroid hormone, PCDEs could bind to thyroid hormone receptor and alter thyroid function. Furthermore, PCDEs might be metabolized to toxic metabolites. In the environment, it is possible that photolysis converts PCDEs to toxic PCDDs and PCDFs. 

The use of chlorophenols was restricted after these formulations were shown to contain toxic PCDDs and PCDFs as impurities and nowadays their use has totally discontinued in many countries [49]. The estimated total amount of chlorophenols used yearly in many countries was thousands of tonnes before they were banned. At the end of the 1970s the annual world production of chlorophenols was 150,000 tonnes [15]. de Boer andDenneman [46] have estimated, based on production figures of chlorophenols and the amount of PCDEs in chlorophenols, that 250-2500 tonnes of PCDEs have been released into the environment via this route. 

In the last twenty years, PCDD and PCDF were identified as by-products in many industrial processes which involve chlorine or chlorinated compounds. Additionally both groups of compounds were found to be formed in a broad range of combustion processes, including accidental fires. Municipal waste incineration is particularly considered to be a very important, if not the most important, of the identified source of environmental dibenzo-p-dioxin and dibenzofuran contamination. As a consequence, the evaluation and close control of new and existing installations for their dioxin releases has become a major concern. Based on this relative importance of municipal waste incinerators, and taking into account the relative toxicity data actually available for PCDD and PCDF, it was decided to prepare and certify a crude fly ash extract (CRM 429) for the twelve more toxic PCDD and PCDF [18,19]. 

Table I. The Most Toxic PCDD and PCDF Isomers...

In most biological samples only the most toxic PCDD and PCDF isomers were found, see Tables I-VI. In addition, two Cl7 and two Cl8 congeners were also found. An exception from this general behaviour is the crustaceans, where a multitude of isomers could be identified. 

In this study, highly toxic PCDD and PCDF congeners were more easily... 

These results are critical for evaluating the efficancy of chlorophyll as an agent for decreasing intake of toxic PCDD and PCDF congeners. Thus, chlorophyll administration enhanced the fecal excretion of PCDD and PCDF congeners and reduced PCDD and PCDF congeners absorption in rats administered the dioxin mixture. 

Coplanar PCBs, PCDDs, and PCDFs express Ah-receptor-mediated toxicity (Chapter 6, Section 6.2.4). Binding to the receptor leads to induction of cytochrome P4501 and a number of associated toxic effects. Again, toxic effects are related to the extent of binding to this receptor and appear to be additive, even with complex mixtures of planar polychlorinated compounds. Induction of P4501A1/2 has been widely used as the basis of a biomarker assay. Residue data can be used to estimate TEQs for dioxin (see Chapter 7, Section 7.2.4). 

The number of chlorine atoms in each molecule can vary from one to eight. Among the possible 210 compounds, 17 congeners have chlorine atoms at least in the positions 2, 3, 7 and 8 of the parent molecule and these are the most toxic, bioaccumulative and persistent ones compared to congeners lacking this configuration. All the 2,3,7,8-substituted PCDDs and PCDFs plus coplanar PCBs (with no chlorine substitution at the ortho positions) show the same type of biological and toxic response. 

There are 210 different isomeric possibilities, 75 of which are PCDDs and 135 are PCDFs. The toxicity of these isomers varies greatly, and only 15 exhibit extreme toxicity, the most toxic of which is 2,3,7,8-tetrachlorodibenzodioxin (2,3,7,8-TCDD). The toxicity of the other isomers is therefore expressed as a toxicity equivalent of 2,3,7,8-TCDD. The PCDDs and PCDFs are poorly water soluble but are fat soluble and are therefore able to accumulate in tissue fat, thus allowing them to bio-accumulate in living organisms. The origin of dioxins in the pulp and paper industry is not entirely clear. They may be produced from the chlorination of dibenzodioxin which may be present in recycled oils used to make defoamers, but they may also arise from wood chips which have been treated with polychlorophenol to prevent sap stain formation. It is also possible that they are derived from lignin by chlorination. Dioxins are also known to be formed naturally by combustion of material such as wood, and forest fires have been particularly identified as a likely major cause of dioxin emissions. 

There is a pronounced difference in biological and toxicological effects between different PCDD and PCDF isomers which is contradictory to the chemical and physical properties of these compounds discussed above. The isomers with the highest acute toxicity are 2,3,7,8-tetra-CDD, 1,2,3,7,8-penta-CDD, 1,2,3,, 7 8-, 1,2,3,6,7,8- and 1,2,3,7,8,9-hexa-CDD, 2,3,7,8-tetra-CDF, 1,2,3,7 8 and 2,3,, 7 8-penta-CDF and 2,3,U,6,7,8-hexa-CDF, see Figure 2. All these isomers have their four lateral positions substituted for chlorine, and they all have LD,-0 values in the range 1-100 yg/kg for the most sensitive animal species (15-17) The same isomers have been reported to have the highest biological potency (l8). 

Isomers of PCDDs and PCDFs vary highly in their acute toxicity and biological activity (15-19). A factor of 1 000-10 000... 

Polychlorinated Dibenzo-(p)-Dioxins and Dibenzo-Furans. Another group of compounds that we need to specifically address are the polychlorinated dibenzo-p-dioxins (PCDDs) and dibenzo-furans (PCDFs) (Fig. 2.15). The PCDDs and PCDFs are not intentionally produced but are released into the environment from various combustion processes and as a result of their occurrence as unwanted byproducts in various chlorinated chemical formulations (e.g., chlorinated phenols, chlorinated phenoxy herbicides see Alcock and Jones, 1996). Because some of the PCDD and PCDF congeners are very toxic (e.g., 2,3,7,8-tetrachloro dibenzo-p-dioxin, see margin), there have been and still are considerable efforts to assess their sources, distribution, and fate in the environment. Similarly to the PCBs or DDT (see above), the PCDDs and PCDFs are highly hydrophobic and very persistent in the environment. It is therefore not surprising that they have also been detected everywhere on earth (Brzuzy and Hites, 1996 Lohmann and Jones, 1998 Vallack et al., 1998). Finally, we should note that polybrominated diphenylethers (PBDEs, see margin) that, like the PBBs (see above), are used as flame retardants, are of increasing environmental concern (de Boer et al., 2000). 

Chlorinated dimeric impurities such as PCDDs and PCDFs are frequently present in contaminated sites. These impurities are very toxic and recalcitrant towards biodegradation and, thus, make the completion of site decontamination very difficult. 

PCDDs and PCDFs Toxic Equivalency Factor PCBs Toxic Equivalency Factor ... 

PCDDs and PCDFs (PCDD/Fs) are often just called dioxins . The number of chlorine atoms in each molecule can vary from 1 to 8, and there are 75 and 135 congeners for PCDDs and PCDFs, respectively. The congeners with chlorine substitutions in the 2, 3, 7, and 8 positions are thought to have dioxin-like toxicity. PCDD/Fs are formed as unwanted... 

Ahlborg UG, Hanberg A. 1992. Toxicokinetics of PCDDs and PCDFs of importance to the development of human risk assessment. Toxic Substances Journal 12 197-211. 

Duarte-Davidson R, Harrad SJ, Allen SC, et al. 1992. The relative contribution of individual PCBs, PCDDs, and PCDFs to toxic equivalent values derived from bulked human breast milk samples from the UK. Chemosphere 25 1653-1663. 

Van den Berg M, Bimbaum L, Bosveld ATC, et al. 1998. Toxic equivalency factors (TEFs) for PCBs, PCDDs, and PCDFs for humans and wildlife. Environ Health Perspect 106(12) 775-792. 

Since dioxins and furans have varying levels of toxicity, emissions of mixtures of these compounds are typically expressed in TEQs (Toxic EQuivalents). TEQs relate the toxicity of all dioxin and furan compounds to the known toxicity of 2,3,7,8-TCDD using a weighting scheme adopted by the EPA and most European countries.1,2 Therefore, a quantity of combined PCDDs and PCDFs... 

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