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 Interspecies. An additional factor of 10 is used in human health risk
assessment to extrapolate from the results of animal studies and predict
concentrations that will produce adverse effects in humans. This factor
incorporates both toxicokinetic and toxicodynamic considerations. In the case of
RfCs, dosimetric adjustments are made to experimental animal NOAELs. These
dosimetric adjustments are considered less uncertain than for the RfD; thus, a
factor of 3 instead of 10 is applied. In ecological risk assessment, a factor of 10
may also be used to extrapolate from results determined for a laboratory test
species and predict the dose expected to cause an adverse effect in a related
wildlife species.
Various empirical data have been used to develop methods to make
taxonomic extrapolations about the sensitivity of various species, genera,
families, orders, or functional groups to contaminants (Suter 1993). Differences
between species in sensitivity to contaminants have been studied extensively for
certain contaminants, such as pesticides. In general, uncertainties associated with
extrapolating between orders, classes, and phyla tend to be higher than for
extrapolation between species within a genus, or between genera within a family
(Suter 1993; USEPA 1998a). Uncertainty factors of 10 for taxonomic variance
are, in some cases, based on the finding that the lowest LC50 for a subset of test
species (Suter 1993). However, given that most species have not been tested,
actual differences may be greater than an order of magnitude. Therefore, the
magnitude of uncertainty associated with differences between an appropriate,
reasonably sensitive test species and a particular species of concern could be
greater than an order of magnitude and is ranked as moderate.
Acute-to-chronic or subchronic-to-chronic. Unless the NOAEL used in
determining an RfD and/or RfC is based on a chronic study, USEPA applies an
uncertainty factor of 10 to account for anything less than lifetime exposures. This
factor is also used in ecological risk assessment. Uncertainty associated with this
extrapolation has been shown to be moderate (Kenaga 1982).
LOAEL to NOAEL. Both human health noncarcinogenic toxicity estimates
and ecological toxicity reference values incorporate an uncertainty factor of 10
when extrapolating from an LOAEL to an NOAEL. Uncertainty associated with
this extrapolation can be easily quantified and is expected to be low.
Although the uncertainty associated with each individual extrapolation is low
to moderate, use of several uncertainty factors together could result in a
significant overestimate of risk that is highly uncertain.
Timing of exposure. Exposure during sensitive life stages of either test
organisms or humans can influence the type and magnitude of toxic effects.
Generally, no uncertainty factor is applied to account for this potential effect. It
remains as a source of uncertainty in the risk assessment. This source of
uncertainty is not ranked because few data exist to measure this uncertainty
across a broad spectrum of chemicals and potential adverse outcomes. It would
be moderately difficult to undertake studies needed to reduce this uncertainty,
assuming laboratory assays could be used rather than epidemiological
investigations.
49
Chapter 5 Uncertainty in Tier IV Risk Assessments
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