Species differences TCDD toxicity

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. 

TCDD is 0.6 yg/kg of body weight for male guinea pigs. Table I shows the acute toxicity of TCDD and the considerable species-dependence of TCDD (9). Reasons for these large differences may be different biochemical elimination or degradation pathways for different animals. 

The biologic factors that account for this large difference (up to 5000 fold) in species susceptibility in acute toxicity have not yet been defined. The other laboratory animal species (mouse, rat, monkey, rabbit and dog) in which TCDD has been tested have single dose oral LD50 values that are found to be somewhere between the most sensitive species (guinea pig) and the least sensitive species (hamster). 

Because TCDD is widely distributed in the environment and because it is very toxic there have been several studies of its bioconcentration using different species of fish and different experimental approaches. Values of Kb from uptake and excretion rate constants ranged from 9.27 x lO to 159 x lO, considerably less than the value derived from the data used above. The major differences were observed in values reported for ki, which varied from 108 to 2300 mL g day . This discrepancy may reflect limitations of the experimental procedures used and may also be influenced by the available concentration of TCDD. If concentrations used are higher than the reported solubility or reduced by the presence of DOM, an incorrect value for the actual concentration in solution will affect the estimate of ki. It is clear that the determination of Kb for compounds of low 5w is a significant experimental challenge. 

Table 4.1 shows that the toxicity data vary in a huge range for different animal species, which mandates extreme caution in drawing conclusions. Human toxicity data are not known for dioxins, but some observations imply that people are more resistant to poisoning than hamsters. The right side of the table shows toxicity data for other substances. It is clear that TCDD is not among the most poisonous substances. 

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