Dioxins toxic effects

Fanelb, R., M.P. Bertoni, M.G. Castelli, C. Chiabrando, G.P. Martelh, A. Noseda, S. Garattini, C. Binaghi, V. Marazza, and F. Pezza. 1980b. 2,3,7,8-Tetrachlorodibenzo-p-dioxin toxic effects and tissue levels in animals from the contaminated area of Seveso, Italy. Arch. Environ. Contam. Toxicol. 9 569-577. 

PCDDs and PCDEs, together with coplanar PCBs, can express Ah-receptor-mediated toxicity. TCDD (dioxin) is used as a reference compound in the determination of TEFs, which can be used to estimate TEQs (toxic equivalents) for residues of PHAHs found in wildlife samples. Biomarker assays for Ah-receptor-mediated toxicity have been based on the induction of P450 lAl. TEQs measured in field samples have sometimes been related to toxic effects upon individuals and associated ecological effects (e.g., reproductive success). 

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). 

Van den Berg, M., B.L.H.J. Craane, T. Sinnige, S. Van Mourik, S. Dirksen, T. Boudewijn, M. Van der Gaag, I.J. Lutke-Schipholt, B. Spenkelink, and A. Brouwer. 1994. Biochemical and toxic effects of polychlorinated biphenyls (PCBs), dihcnzo-p-dioxins (PCDDs) and dibenzofurans (PCDFs) in the cormorant (.Phalacrocorax carbo) after in ovo exposure. Environ, Toxicol. Chem. 13 803-816. 

Van der Weiden, M.E.J., R. Bleumink, W. Seinen, and M. Van den Berg. 1994. Concurrence of P450 1A induction and toxic effects in the mirror carp (Cyprinus carpio), after administration of a low dose of 2,3,7,8-tetrachlorodibenzo-p-dioxin. Aquat. Toxicol. 29 147-162. 

Chlorinated organic compounds (dioxins, other halocarbons) Combustion of municipal wastes, paper processing, cleaning solvents Toxic effects including birth defects, reproductive failure, cancer, and systemic poisoning. 

It should be realized that with the exception of a few groups of chemicals (such as some organophosphorous and carbamate pesticides as well as some polychlorinated dibenzo-p-dioxins (PCDDs), polychlorinated dibenzofurans (PCDFs), and polychlorinated biphenyls (PCBs), precise mechanistic information on their toxic effects are scarce. In realizing that the exact molecular mechanism is not known for most chemicals the term mode of action is used to describe toxicides that appear to be similar albeit the mechanism is not known in detail, see also Section 4.2.6. For several groups of endocrine disrupters this terminology seems appropriate. 

A particularly potent immunosuppressive chemical is TCDD, dioxin. This inhibits the differentiation of T cells by damaging the epithelial cells in the cortex of the thymus. These cells are involved in the maturation of T cells. A receptor is involved with this toxic effect, the AHR receptor, to which TCDD binds very strongly. The receptor is expressed in the thymus. Mice, which to do not express this receptor, do not show this particular toxic effect of TCDD even at 10 times higher doses. 

The toxic effects associated with PCN exposures in humans and wildlife are, in general, characteristic of effects due to chlorinated hydrocarbons such as 2,3,7,8-TCDD. For instance, chloracne, vitamin A depletion, edema and liver damage have been observed in animals exposed to TCDD. The human toxicity and mechanistic relationship of PCNs to TCDD may be useful in understanding these classes of compounds. Particularly, acute and subacute exposures of humans and cattle to PCNs may provide important clues to the toxic effects at high levels for other dioxin-like compounds. 

CDDs and the structurally related CDFs and dioxin-like PCBs are of concern to ATSDR because of the potential of these chemicals to harm health at relatively low doses. As discussed in Section 2.5, many of the toxic effects of these compounds appear to be mediated by a common mechanism, and CDDs frequently occur with CDFs in the environment. Therefore, due to the common mechanism of toxicity, total toxicity of a CDD/CDF mixture probably results from the added contribution (not necessarily linear) of both classes of chemicals. Because of this, the complex issue of appropriate methodology for quantitatively assessing health risks of CDDs and CDFs is currently being evaluated by ATSDR. Additional information on toxic interactions between CDDs and CDFs, as well as PCBs, would facilitate health risk assessment of this class of chemicals. 

CAS = Chemical Abstracts Services CDDs = chlorinated dibenzo-p-dioxins DOT/UN/NA/IMCO = Department of Transportation/United Nations/North America/lnternational Maritime Dangerous Goods Code EPA = Environmental Protection Agency HSDB = Hazardous Substances Data Bank NCI = National Cancer Institute NIOSH = National Institute for Occupational Safety and Health OHM/TADS = Oil and Hazardous Materials/Technical Assistance Data System RTECS = Registry of Toxic Effects of Chemical Substances... 

Holcomb M, Yao C, Safe S. 1988. Biologic and toxic effects of polychlorinated dibenzo-p-dioxin and dibenzofuran congeners in the guinea pig Quantitative structure-activity relationships. Biochem Pharmacol 37 1535-1539. 

Data are available suggesting that DEHP might act as an antagonist for the hepatic damage caused by other chemicals. DEHP was combined with 2,3,7,8-tetrachlorodibenzo-/ -dioxin (TCDD) to determine if the hypolipidemic effects of DEHP could counteract the hyperlipidemic effects of the TCDD (Tomaszewski et al. 1988). Pretreatment with DEHP mitigated many of the toxic effects of TCDD. 

Perhaps the most renowned example is the extensively-used 2,4,5-T (2,4,5-trichlorophenoxyacetic acid), or rather the 2,3,7,8-tetrachlorodibenzo- -dioxin (TCDD) impurity which sometimes accompanies it. During massive use of the herbicide as a defoliant in the Vietnam war, TCDD was found almost by accident to be one of the most toxic synthetic substances ever tested. Soon, it was shown to be present in domestic 2,4,5-T as well as in the chemical warfare agents. Tests in laboratory animals demonstrated that some of the observed levels indeed were quite high enough to cause toxic effects (32). 

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