Areas of Uncertainty in Toxicity Assessments
* Uncertainty as to the relative sensitivity of humans as compared to laboratory animals. Typically a number
of studies are available, including studies showing no adverse effects, as a basis for the toxicity assessment. Sometimes
there are data Indicating the most appropriate study, but often there is no definitive answer as to which species, strain, or sex
Is the most comparable to humans.
* Uncertainty as to whether or not a particular chemical will have any potential to be a human carcinogen
at low doses. In some cases, the use of excessively high doses in animal studies leads to a carcinogenic response in
animals that is an artifact of the high dose and therefore not relevant to humans. There may be no risk to humans at expected
* Uncertainty as to whether or not, on a chemical-by-chemical basis, there is a dose threshold for the
carcinogenic effects observed at high doses. Examination of biological mechanisms implies that, at least for some
chemicals, there is a dose threshold below which no carcinogenic effects would be expected in any finite population.
* Uncertainty in the shape of the dose-response curve at low doses (see Figure 2). For chemicals that may have
the potential to cause cancer at high doses, it is not known what the dose-response curve looks like at the low doses
encountered at Superfund sites.
* Uncertainty In the determination of equivalent doses between animals and humans. This factor contains
two components: the calculation of equivalent doses relative to administered dose in the same species, and the calculation
of doses resulting in the same sensitivity in different species.