Toxicity of TCDD

The studies reported here confirmed the high toxicity of 2,3,7,8-TCDD. In addition, some perspective of the relative toxicides of... 

Reinecke, A.J. and R.G. Nash. 1984. Toxicity of 2,3,7,8-TCDD and short-term bioaccumulation by earthworms (Oligochaeta). Soil Biol. Biochem. 16 45A9. 

The above results demonstrated hematological effects in animals following CDD exposure however, the observed changes in the red and white blood cell counts were nonspecific and were probably due to the broad systemic toxicity of 2,3,7,8-TCDD rather than to a direct effect on the hematological system. 

These genetic data strongly support the role of the Ah receptor in mediating the toxicity of 2,3,7,8-TCDD and related halogenated aromatic hydrocarbons. However, it has become clear that a comparison of the properties of the Ah receptor across species and tissues indicates that it is difficult to account for the species-specific sensitivity and diversity of the biological effects of 2,3,7,8-TCDD by characteristics of... 

Extensive evidence suggests that the immune system is a sensitive target for toxicity of 2,3,7,8-TCDD and structurally related halogenated aromatic hydrocarbons (Kerkvliet 1995). Exposure to 2,3,7,8-TCDD can increase susceptibility to bacterial (Thigpen et al. 1975 Thomas and Hinsdill 1979 White et al. 1986), viral (Clark et al. 1983 House et al. 1990), parasitic (Tucker et al. 1986), and neoplastic disease (Luster et al. 1980). However, the specific immunological functions affected by 2,3,7,8-TCDD in most of the host-resistance models have not been fully defined. Thymic involution is characteristic of exposure to 2,3,7,8-TCDD and structurally related chemicals in all species examined. There is experimental evidence showing that immune suppression in rodents occurs at lower doses of... 

Reproductive Effects. The weaknesses of the epidemiology studies examining reproductive end points limits drawing conclusions regarding the reproductive toxicity of 2,3,7,8-TCDD in humans. 

Subsequent sections of this chapter (Sections 2.7, 2.8, and 2.10) discuss the available information on biomarkers, interactions, and methods for reducing toxic effects. Most of the available information is from adults and mature animals no child-specific information was identified, with the possible exception of biomarker data. However, there are some data to suggest that interactions with PCBs and CDFs may influence the developmental toxicity of 2,3,7,8-TCDD. Data from children living in Seveso suggest that serum 2,3,7,8-TCDD levels are reflective of exposure levels and are a sensitive indicator of past exposure. Likewise, it is likely that the available information in adults on interactions and methods for reducing toxic effects will also be applicable to children. 

Children s Susceptibility. A limited number of human studies have examined health effects of CDDs in children. Data from the Seveso accident suggest that children may be more susceptible to the dermal toxicity of 2,3,7,8-TCDD (chloracne), but it is not known if this would be the case for other effects. Follow-up medical surveillance of the Seveso children (including measurement of serum 2,3,7,8-TCDD levels) would provide information on whether childhood exposure would pose a risk when the individual matures and ages. The available human and animal data provide evidence that 2,3,7,8-TCDD can cross the placenta and be transferred to an infant via breast milk. Although information on the developmental toxicity of CDDs in humans is limited, there are extensive animal data that the developing... 

Dencker L, Hassoun E, D Argy R, et al. 1985. Fetal thymus organ culture as an in vitro model for the toxicity of 2,3,7,8-TCDD and its congeners. Mol Pharmacol 27 133-140. 

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... 

The term TEQ is an abbreviation for TCDD equivalents. If the toxicity of 2,3,7,8-TCDD is 1, the toxicity of other congeners is reduced by a weighting factor. The extreme variation of potency among the TCDDs, TCDBs, and PCBs makes this necessary when risk assessments of residues are carried out. The residues are multiplied by these factors. The residue of octachlo-rodibenzodioxin is regarded as less potent and is multiplied by 0.001, whereas the concentration of 2,3,7,8-tetrachlorodibenzofuran is multiplied by 0.1, and so forth. 

Table I. Acute Toxicity of 2,3,7,8- TCDD During Oral Administration...

The presence of PCDD in the environment and the acute and chronic toxicity of 2,3,7,8- TCDD and similarly substituted congeners in animals raise concern. How serious should this concern be and what actions are warranted to relieve this concern These questions are addressed by a risk assessment... 

Figure I illustrates some major events which have occurred since production of the chlorophenols began in the United States in the mid-1930 s. Although accidents have occurred periodically and adverse health effects related to dioxin exposure have been recognized in exposed workers, it was not until the 1970 s that the problems received public attention. During that decade, animal studies demonstrated the severe toxicity of 2,3,7,8-TCDD and it was realized that large numbers of people had potential exposure to...

What is dioxin Dioxin is the collective name of 75 compounds called polychlorodibenzo-p-dioxin and 135 compounds called polychlorodiben-zofiiran. They are toxic but the toxicity of 2,3,7,8-TCDD is the highest. 

The development of toxicity equivalent factors (TEFs) for halogenated aromatic compounds, as proposed by Safe [34], is based on the observed common receptor-mediated mechanism of action of toxic halogenated aromatics. The relative toxicity of 2,3,7,8-TCDD is taken as unity on the TEF scale, and individual TEF values have been derived for the other stereoisomers including PCBs [38]. Recendy, a thermodynamic model for calculating the TEF values for PCBs was reported by Kafafi et al. [39] their model permitted calculation of the dissociation constants of complexes formed between the aryl hydrocarbon receptor and a PCB molecule. McFarland and Clarke [40] have argued that, as the toxicity of individual congeners varies over a range of 10, the determination of total PCB content is of... 

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