Exposure, TCDD

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]. 

Daily exposure in dose equivalents, using 17/ -estradiol aetivity for oestrogenieity (EQ) and TCDD for anti-oestrogenie aetivity (TEQ). 

A similar rclea.se occurred in Duphar, India in 1963, after which the plant was disassembled brick by brick, encased in concrete and dumped into the ocean. Less than 200 grams of TCDD w ere released at Duphar, and the contamination was confined to the plant. Fifty men did the clean nn four eventually died from the exposure. 

There are even receptors that are known to become activated only due to interaction with a synthetic chemical, and no physiological agonist for such a receptor has been characterized. A model receptor in this class is the so-called Ah receptor complex that becomes activated subsequent to its exposure to 2,3,7,8-tetrachlorodibenzo-p-dioxiu (TCDD). Activation of the. Ah receptor... 

TCDD is the most potent inducer of chloracne. This has been well known since the accident in Seveso, Italy, in 1976 in which large amounts of TCDD were distributed in the environment subsequent to an explosion in a factory that produced a chlorophenoxy herbicide, 2,4,5-T. TCDD is an impurity produced during the production of 2,4,5-T. The most common long-term effect of TCDD exposure was chloracne. Exposed individuals also suffered increased excretion of porphyrins, hyper-pigmentation, central nervous system effects, and liver damage and increased risk of cancer was a long-term consequence of the exposure. In addition to TCDD, polychlorinated biphenyls (PCBs), polychlorinated dibenzofurans, and polychloronaphthalens cause chloracne as well as other effects typical of TCDD. 7i... 

Custer, C.M, Custer, T.W., and Rosiu, C.J. et al. (2005). Exposure and effects of 2,3,7,8-TCDD in tree swallows nesting along the Woonasquatucket River, Rhode Island, USA. Environmental Toxicology and Chemistry 24, 93-109. 

Similar results were obtained when TCDD in methanol was exposed to natural sunlight in sealed borosilicate glass tubes or beakers (Figure 3). After about 36 hours exposure, a yellow non-volatile gum was obtained as the sole product by evaporation of the solvent. It showed no UV absorption and did not seem to retain the benzenoid chromophore ... 

TAetection of the highly potent impurity, 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) in the herbicide 2,4,5-trichlorophenoxyacetic acid (2,4,5-T), necessitated an environmental assessment of the impact of this contaminate. Information was rapidly needed on movement, persistence, and plant uptake to determine whether low concentrations reaching plants, soils, and water posed any threat to man and his environment. Because of the extreme toxicity of TCDD, utmost precautions were taken to reduce or minimize the risk of exposure to laboratory personnel. Synthesis of uniformly labeled C-TCDD by Muelder and Shadoff (I) greatly facilitated TCDD detection in soil and plant experiments. For unlabeled experiments it seemed wise to use only small quantities of diluted solutions in situations where decontamination was feasible and to rely on the sensitivity afforded by electron capture gas chromatography... 

Plant uptake is one of several routes by which an organic contaminant can enter man s food chain. The amount of uptake depends on plant species, concentration, depth of placement, soil type, temperature, moisture, and many other parameters. Translocation of the absorbed material into various plant parts will determine the degree of man s exposure—i.e., whether the material moves to an edible portion of the plant. Past experience with nonpolar chlorinated pesticides suggested optimal uptake conditions are achieved when the chemical is placed in a soil with low adsorptive capacity e.g., a sand), evenly distributed throughout the soil profile, and with oil producing plants. Plant experiments were conducted with one set of parameters that would be optimal for uptake and translocation. The uptake of two dioxins and one phenol (2,4-dichlorophenol (DCP)) from one soil was measured in soybean and oats (7). The application rates were DCP = 0.07 ppm, DCDD 0.10 ppm, and TCDD = 0.06 ppm. The specific activity of the com-... 

For some toxins it is possible to demonstrate an apparent improvement in functional response at levels of exposure which are below a threshold. This effect, which has been termed hormesis , is most effectively demonstrated in the consistently improved longevity of animals whose caloric intake is restricted rather than allowing them to feed ad lib (Tannenbaum, 1942). Clearly in this instance, the observed effects are the result of exposure to a complex mixture of chemicals whose metabolism determines the total amount of energy available to the organism. But it is also possible to show similar effects when single chemicals such as alcohol (Maclure, 1993), or caffeic acid (Lutz et al., 1997) are administered, as well as for more toxic chemicals such as arsenic (Pisciotto and Graziano, 1980) or even tetrachloro-p-dibenzodioxin (TCDD) ( Huff et al., 1994) when administered at very low doses. It is possible that there are toxins that effect a modest, reversible disruption in homeostasis which results in an over-compensation, and that this is the mechanism of the beneficial effect observed. These effects would not be observed in the animal bioassays since to show them it would be necessary to have at least three dose groups below the NOAEL. In addition, the strain of animal used would have to have a very low incidence of disease to show any effect. 

Although the effects of chronic exposure of humans to low levels of POPs are difficult to predict, some biological effects have been described. For example, exposure of children to PCBs and PCDD/Fs may be linked to an elevated risk for infectious diseases. Exposure of pregnant women to PCDD/Fs may cause lower fertility in their male offspring. The adverse effects to human health of acute and chronic exposure of high concentrations of POPs, especially among industrial workers exposed to daily intakes of chemicals, are more evident. Elevated concentrations of DDE and TCDD have been associated with the development of cancers such as breast cancer, leukaemia and thyroid cancer. Dioxin exposure may also be associated with immunotoxicity, reproductive diseases and neurotoxicity. Extreme exposure to chlorinated compounds has resulted in death [101]. 

TCDD concentrations in eggs of seven species after exposure as fertilized eggs to nominal concentrations of 9-285 ng 2,3,7,8-TCDD/L for up to 540 h. Lowest observed effect concentration (LOEC) in ng/kg FW associated with adverse effects on su rvival or growth 32 days post exposure vs. no observed effect concentration (NOEC) in ng/kg FW Lake herring, Coregonus artedi 270 vs. 175 Fathead minnow, Pimephales promelas ... 

Juveniles (0.4 g BW) exposed for 28 days to 0.038, 0.079, 0.176, 0.382, or 0.789 ng 2,3,7,8-TCDD/L (parts per trillion) followed by 28 days in clean water Significant adverse effects on survival, growth, and behavior during exposure and depuration at all concentrations tested. The lowest concentration group tested (0.038 ng/L) — which was the least affected — had 45% dead after day 28 of depuration and a whole-body BCF of 39,000 after exposure and about 26,000 after depuration. Controls had 93% survival 30... 

In ovo exposure to dioxins is associated with development of grossly asymmetric avian brains, especially the forebrain and tectum. Brain asymmetry was observed in herons, cormorants, eagles, and chickens exposed to 2,3,7,8-TCDD under controlled conditions. Asymmetry appears with increasing frequency and severity in embryos and hatchlings exposed to increasing doses of... 

Accumulation of 2,3,7,8-TCDD is reported in the liver of rats during lifetime exposure to diets containing 0.022 pg 2,3,7,8-TCDD/kg (Newton and Snyder 1978), or when administered orally at 0.01 pg/kg body weight once a week for 45 weeks (Cantoni et al. 1981). Liver residues of rats fed 2,3,7,8-TCDD were 0.54 pg/kg, or about 25 times dietary levels livers of rats dosed orally contained 1.05 pg/kg, or about 2.3 times the total dose received on a unit weight basis. Unlike toxicity, elimination rates of accumulated 2,3,7,8-TCDD were within a relatively narrow range. The estimated retention times of 2,3,7,8-TCDD in small laboratory mammals (rats, mice, guinea pigs, and... 

Newton, M. and S.P. Snyder. 1978. Exposure of forest herbivores to 2,3,7,8-tetrachIorodibenzo-p-dioxin (TCDD) in areas sprayed with 2,4,5-T. Bull. Environ. Contam. Toxicol. 20 743-750. 

Young, A.L. and L.G. Cockerham. 1985. Fate of TCDD in field ecosystems assessment and significance for human exposures. Pages 153-171 in M.A. Kamrin and P.W. Rodgers (eds.). Dioxins in the Environment. 

In all tested organisms, PCBs — especially PCBs with 2,3,7,8-TCDD-like activity — adversely affected patterns of survival, reproduction, growth, metabolism, and accumulation. Common manifestations of PCB exposure in animals include hepatotoxicity (hepatomegaly, necrosis), immunotox-icity (atrophy of lymphoid tissues, suppressed antibody responses), neurotoxicity (impaired behavior and development, catecholamine alterations), increased abortion, low birth weight, embryolethality, teratogenicity, gastrointestinal ulceration and necrosis, bronchitis, dermal toxicity (chloracne, edema,... 

Faith, R.E. and Moore, J.A., Impairment of thymus-dependent immune functions by exposure of the developing immune system to 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD), J. Toxicol. Environ. Health, 3, 451, 1977... 

FIGURE 7.4 (A) Donor CD4+T cell proliferation, as reflected by dilution of the fluorescence associated with CFSE, is not altered by TCDD exposure. Changes in expression ofT cell activation markers (B) CD62L and (C) CD25, are induced by TCDD exposure and are dependent on cell division. Data represent donor CD4+ T cells responding to alloantigen in F1 hosts 48 hours after adoptive transfer. F1 host mice were treated with vehicle or TCDD one day prior to injection of CFSE-labeled donorT cells. Adapted from Funatake et al., 2005. 

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