Hazard Assessment and Contaminated Sites - Dealing with Contaminated Sites: From Theory Towards Practical Application - page 531

A number of toxicology text books include chapters on pharmacokinetics
and toxicology assessment. The publication, Science and Judgement in Risk
Assessment (National Academy of Sciences (NAS)/National Research Council
(NRC) 1994), has useful sections on the impact of pharmacokinetic information
in Risk Assessment.
12.3.5.8 Interspecies Scaling of Doses
Where animal bioassays are the source of data, an estimate or measure of the human equiva-
lent dose is required for assessing the health risks posed by contaminant. To derive a human
equivalent dose from animal data, the preferred option is to use toxicokinetic data that
provides biologically equivalent doses (NHMRC 1999 , p. 65).
There are several methods for undertaking scaling of doses including
physiologically-based, pharmacokinetic modelling and other models, scaling on a
body weight basis, and allometric scaling (body weight raised to the three-quarter
power) (ibid). As there is often inadequate data (probably the majority of cases),
interspecies differences in physiological and biochemical processes are accounted
for by using a generic interspecies factor (ibid).
12.3.5.9 Route-to-Route Scaling
Often the toxicological data are not available for the most appropriate route of expo-
sure for humans. For example, only oral carcinogenicity data may be available,
whereas exposure to contaminants by oral, dermal and inhalational routes may be
important. Thus, extrapolation from one route of exposure to another may be nec-
essary; this needs to be assessed on a case-by-case basis depending on the available
data.
One important consideration in route-to-route extrapolation is determining
whether the adverse human health effects are localised to the site of exposure
in the body (e.g. carcinomas occurring in the nose or lungs from inhalation) or
whether they are a consequence of systemic distribution (e.g. skin cancers arising
from arsenic ingestion or some types of leukaemias from benzene inhalation). If the
effects are localised to the site of exposure in the body and not a consequence of the
systemic distribution of the contaminant, then it may be inappropriate to extrapolate
the dose to a different route of exposure. If the effects are consequent to absorption
and systemic distribution of the contaminant, then dose scaling between routes of
exposure needs to account for the bioavailability of the contaminant by the different
routes.
Therefore, bioavailability is an important consideration when extrapolating the
applied dose to different routes of exposure. However, additional factors may need to
be considered, such as physiological differences between species when extrapolat-
ing, for example, from inhalational exposure in animals to oral exposure in humans
or vice versa. The assessor should include information about the bioavailability of
the contaminant in the experimental studies in the final report.