Mammals dioxins

In mammals, phenobarbital and phenytoin increase serum ceruloplasmin concentrations (Aaseth and Norseth 1986). Chronic copper poisoning in sheep is exacerbated when diets contain heliotrope plants (Heliotropium sp., Echium spp., Senecio sp.). Aggravated effects of the heliotrope plants include reduced survival and a twofold to threefold increase in liver and kidney copper concentrations when compared to control animals fed copper without heliotropes (Howell et al. 1991). Rats given acutely toxic doses of 2,3,7,8-tetrachlorodibenzo-para-dioxin had elevated concentrations of copper in liver and kidney because of impaired biliary excretion of copper (Elsenhans et al. 1991). Morphine increases copper concentrations in the central nervous system of rats, and dithiocarbam-ates inhibit biliary excretion (Aaseth and Norseth 1986). In human patients, urinary excretion of copper is increased after treatment with D-penicillamine, calcium disodium EDTA, or calcium trisodium diethylenetriamine penta acetic acid (Flora 1991). 

The main depot for dioxin accumulation in mammals is the liver and adipose tissue. When dioxin is fed to rodents with fodder, about 10% of the dose comes in the liver. Should this toxic agent be applied on rat skin, 13% of the dose is absorbed in blood already in 5 hours, and 10% remains on skin surface. 

The TEF concept has gained wide acceptance and many different schemes have been proposed. Nowadays, the use of the TEFs for dioxins, dibenzofurans and PCBs for humans and mammals suggested by WHO is often recommended (van den Berg et al., 1998). The TEF scheme includes a kind of safety factor, as the TEF values are rounded upwards. 

However, no studies on fetal exposure are available for setting TEFs. Thus there is a need for dose-response studies of the critical effects, based on synthetic mixtures reflecting the human exposure situation. The WHO TEFs for dioxins, dibenzofurans and PCBs for humans and mammals are given in Table 3. 

In general, our studies with cytochrome P-450-dependent metabolism have emphasized the similarity of the hepatic MFO system in marine fish to that found in mammals. Thus, in the little skate (Raja erinaoea), a marine elasmobranch, enzyme activity is localized in the microsomal fraction, requires NADPH and molecular oxygen for maximum activity, and can be inhibited with CO (1, 2). Moreover, when hepatic microsomes from the little skate were solubilized and separated into cytochrome P-450, NADPH-cytochrome P-450 reductase, and lipid fractions, all three fractions were required for maximal MFO activity in the reconstituted system (3). We have also found, as have others, that the administration of polycyclic hydrocarbons (3-methylcholanthrene, 1,2,3,4-dibenzanthracene [DBA]), 2,3,7,8-tetrachlorodibenzo-p-dioxin... 

The dioxin toxic equivalency factor (TEF) approach is currently used worldwide for assessing and managing the risks posed by exposure to mixtures of certain dioxin-like compounds (DLCs). World Health Organization-TEF (WHO-TEE) values have been established for humans and mammals, birds, and (For new, refined values, see Ref. 12g.) It should be mentioned that 16 PCBs, the coplanar isomers with nonortho, monoortho, and diortho substitution by chlorine (overall, there are 209 isomers for this class of compounds) show dioxin-like toxic behavior. I-TE values are smaller, in the range of 0.0001-0.1. The most toxic isomers is 3,3, 4,4, 5-pentachlorodiphenyl with I-TE of 0.1. Polybrominated dibenzodioxins and furans with the 2,3,7,8 pattern also show dioxin-like toxicity, but their I-TE values are lower compared to PCDD/F. 

One of the most sensitive mammals to dioxin-like PCB and dioxin exposure is the mink. Effects have been documented in both farmed mink [65,66] and wild mink [67-72], Extensive work was done in the 1970s and 1980s by Auerlich, Ringer, and colleagues [65,66,73-76] that documented the impact of feeding Great Lakes fish to mink. These impacts included reproductive... 

Chlorinated dioxins (CDDs) are a family of compounds that includes some extremely toxic and potent congeners. The two most toxic of the CDDs in mammals are 2,3,7,8-TCDD and 1,2,3,7,8-PeCDD (Buser 1987 Poland and Knutson 1982 Safe 1986 WHO 1997). In general, the more toxic congeners to mammals appear to be the 2,3,7,8-substituted tetra-, penta-, and hexachloro- compounds, (e.g., 2,3,7,8-TCDD, 1,2,3,7,8-PeCDD, 1,2,3,4,7,8-HxCDD, 1,2,3,6,7,8-HxCDD, and 1,2,3,7,8,9-HxCDD)... 

Norstrom RJ, Simon M, Muir DCG. 1990. Polychlorinated dibenzo-p-dioxins and dibenzofurans in marine mammals in the Canadian north. Environ Pollut 66 1-19. 

Data on PCDD and PCDF concentrations in wildlife are scarce and mainly available for aquatic species. OctaCDD, 2,3,7,8-tetraCDD and 1,2,3,7,8-penta-CDD are the most abundant PCDD congeners in marine mammals and 2,3,7,8-tetraCDF and 2,3,4,7,8-pentaCDF the most abundant PCDFs.36 Hexa- and heptachlorinated dioxin and furan concentrations are usually very low in marine mammals and may point to relatively high metabolic and elimination rates.37... 

In humans the major and consistent effect is on the skin. Exposed people suffer from a severe form of acne, known as chloracne, after exposure to dioxin. Changes in the immune system have also been detected in the children exposed at Seveso in Italy and workers exposed at the Coalite plant in the UK. The latter had reduced levels of some immunoglobulins. There is no definitive evidence as to whether humans are more or less sensitive to dioxin than other mammals but the weight of evidence would suggest that they are less sensitive than many. 

---