Species, 2,3,7,8-TCDD toxicity

Ankley et al. (1993) studied the uptake of persistent polychlorinated hydrocarbons by four avian species at upper trophic levels of two aquatic food chains. Concentration of 2,3,7,8-TCDD toxic equivalents (TEQs) were evaluated in Forster s tem and common tem chicks and in tree-swallow and red-winged-blackbird nestlings from several areas in the watershed. Young birds accumulated small concentrations of 2,3,7,8-TCDD and several other 2,3,7,8-substituted CDDs and CDFs, including 1,2,3,6,7,8-HxCDD,... 

While all species lost body weight following treatment with 2,3,7,8-TCDD, other signs of toxicity were species dependent. Ascites was seen in mice. Anorexia, dehydration, depression, emaciation, intestinal hemorrhage, and alopecia were seen in dogs. Certain rabbits treated intra-peritoneally with 2,3,7,8-TCDD developed skin lesions typical of those associated with acnegens. 

Dioxins are extremely toxic compounds. LD50 for the most toxic dioxin (2,3,7,8-TCDD) at intragastric injection was 0,6-2,0 mcg/kg for guinea pigs, 3000-5000 mcg/kg for various species of hamsters, about 70 mcg/kg for monkeys and 25-45 mcg/kg for rats. 

Whether a toxin is naturally reactive to biological macromolecules or receptors, or requires metabolic activation to produce such a species, e.g. the enzyme-mediated transformation of tremorine (9) to the active parasympathomimetic agent oxotremorine (10), it will usually be subject to chemical or enzymic inactivation in vivo. Interruption of the latter process via appropriate substitution may thus lead to an increase in biological activity or toxicity over that of the parent compound. Perhaps the most striking example of this is provided by the extreme metabolic stability and toxicity of TCDD and the nontoxicity of its de- chloro analogue dibenzodioxin (Table 3). 

By far the most comprehensive research into AHR-related effects of PCDD/Fs on fish was a retrospective analysis of Lake Ontario lake trout reproductive impairment due to AHR-mediated early life stage mortality [16]. This includes blue sac disease as well as sublethal effects, which may increase susceptibility of sac fry and alevins to increased mortality and predation during swim-up. Lake trout are more susceptible to AHR-mediated toxic effects than any other Great Lakes species, with the possible exception of mink. WHO TEFs for fish were used to calculate the 2378-TCDD equivalent (TECegg or TEQ) concentrations in lake trout eggs. The validity of the additive toxicity equivalence model was established through early life stage trout toxicity tests. The WHO fish TEFs are likely to be fairly robust for lake trout, since they were determined primarily from relative potency values for effects in embryos of a related salmonid, rainbow trout, even if the relative sensitivity of the species to 2378-TeCDD toxicity may be different. 

---