Toxic effect of dioxins

There is a very broad range of toxic effects of dioxins. Many of the congeners can induce toxic responses at very low dose. The most sensitive effects are immunosuppression, developmental and reproductive toxicity, as well as neurological behavioral effects. Carcinogenic effects are induced at higher exposure. TCDD was considered a complete carcinogen by the International Agency for Research on Cancer, IARC [115]. 

Nacci, D.E., M. Kohan, M. Pelletier and E. George. Effects of benzo[a jpyrene exposure on a fish population resistant to the toxic effects of dioxin-like compounds. Aquat. Toxicol. 57 203-215, 2002. 

Since no information was available on the specific doses of dioxin that caused or did not cause health effects in humans, we reviewed the data from studies in animals. These studies show that some animal species are more susceptible to the toxic effects of dioxin than others, but we do not know which species responds most like humans ... 

Some scientists have claimed that humans must not be very susceptible to the toxic effects of dioxin because, despite all the exposures in the workplace, the main health effect in humans is chloracne. Although worker populations have had most of the heavy exposures, they may not fully reflect the risks for the general population. In estimating the risks for the general population, we must consider other groups—children, women of childbearing age, the aged, and the infirm. 

The evaluation of health risks is based on the WHO proposal from 1997, which divided PCBs into two groups based on their structure and related toxicity. The first group consists of PCBs able to bind to the Aryl Hydrocarbon Receptor (AHR), which cause toxic effects similar to the toxic effects of dioxins. Among these, the so-called dioxin like PCBs (DL-PCBs), include a total of 12 congeners, four non-ortho and eight mono-ortho PCBs the most important in terms of the toxic potential is congener 126 (3,3, 4,4, 5-pentachlorobiphenyl). The second group consists of the non-dioxin like PCBs (NDL-PCBs), which are characterised... 

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. 

A. V. Epifantsev - Long-term Effects of Dioxin-containing Eco-toxicants Dioxin Disease. In the book Second Congress of Russian Toxicologists. - 2003.- Moscow, p. 99-101. 

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. 

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. 

Giesy, J.P., Kannan, K. (1998). Dioxin-like and non-dioxin-like toxic effects of polychlorinated biphenyls (PCBs) implications for risk assessment. Crit. Rev. Toxicol. 28 511-69. 

The toxic potential of pure dioxins and PCBs is indicated in toxic equivalence factors (TEF) giving the relative toxicity of the relevant dioxin or PCB relative to the toxic effect of 2,3,7,8-TCDD. TEF for different dioxins and furans vary from 0.01 to 1, whereas TEF for the different PCB congeners is much lower (0.0001-0.01) (26, 27). (Figure 8). 

Toxic equivalencies (TEQ) are calculated by multiplying the TEF by the concentration of each of the different congeners present in a sample and adding them up. The TEQ represents the relative toxicity of a dioxin/PCB mixture in terms of the toxic effect of 2,3,7,8-TCDD. 

One toxic effect of the Seveso dioxin exposure was on reproduction. In the first 7 years after the accident, a very high proportion of females (46 females compared to only 28 males) were born to parents who were exposed to the chemical cloud. This was the first time a chemical had been observed to change the sex ratio, implicating dioxin as a hormone disrupter. TCDD is associated with increased fetal loss and reduced birth weight in animal studies. 

Relatively little is known about the effects of dioxins in invertebrates. Controlled laboratory studies with dioxin-contaminated sediments reported no effects on amphipod mortality. Some studies have shown reduced reproductive success in worms and snails. Some invertebrates have been shown to express Ah receptors, but these receptors do not appear to bind dioxins, thus invertebrates are less sensitive to dioxin toxicity. 

Dioxins are unintended by-products of natural events and human-made processes such as manufacturing, incineration, paper and pulp bleaching, and exhaust emissions. Immunotoxic effects of dioxins have been studied primarily with respect to 2,3,7,8-t c t r a c 111 o r o dib e n / o -/ - d i o x i n (TCDD), the most toxic congener of dioxins and an important immunotoxicant (Vos Moore, 1974). 

British Journal of Industrial Medicine 48 234-238, 1991 Neuberger M, Rape C, Bergek S, et al Persistent health effects of dioxin contamination in herbicide production. Environ Res 81 206-214, 1999 O Donoghue JL Cyclic halogenated hydrocarbons and related substances, in Neurotoxicity of Industrial and Commercial Chemicals, Vol II. Edited by O Donoghue JL. Boca Raton, FL, CRC Press, 1985, pp 155-168 Oliver RM Toxic effects of 2,3,7,8 tetrachlorodibenzo 1,4 dioxin in laboratory workers. British Journal of Industrial Medicine 32 49-53, 1975 Ott MG, Holder BB, Olson RD A mortality analysis of employees engaged in the manufacture of 2,4,5-trichlorophenoxyacetic acid. Journal of Occupational Medicine 22 47-50, 1980... 

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