Oral Bioavailability - Dealing with Contaminated Sites: From Theory Towards Practical Application - page 297

where:
(AUC PO ) RM is the area under the curve obtained from the oral administration
of the contaminant in the reference matrix (RM), e.g. water;
(AUC PO ) TM is the area under the curve obtained from the administration of the
contaminant in the test matrix (TM), e.g. soil material.
This ratio is often between 0 and 1 (or 0 and 100%), because the refer-
ence material is chosen according to its physico-chemical properties in order to
maximise absorption, i.e. water with ionisable metal forms or oil for organic
contaminants.
A number of in-vivo animal trials (i.e. tests performed in a living organism)
have been used to assess the bioavailability of soil contaminants, using a variety of
species such as the monkey, pig, rat and rabbit (Drexler and Brattin 2007 ; Ellickson
et al. 2001 ; Freeman et al. 1992 , 1993 , 1994 , 1995 , 1996 ; Roberts et al. 2007b ;
Schroder et al. 2004a ). Unfortunately, rats and rabbits exhibit large differences in
their digestive physiology compared to humans, rats also have a pre-stomach com-
partment with a very specific physiology. Although these models have a long history
of use in toxicological studies etc., the aim for bioaccessibility and bioavailability
studies with respect to contaminated land is to mimic human physiology and model
the interactions occurring between the soil contaminants and the digestive fluids.
In particular the interactions between digestive fluids and the soil are an impor-
tant parameter to consider, the pH of rat digestive fluids is different to humans,
and the practice of coprophagy (rats) and caecotrophy (rabbits), which the habit
of feeding on excrement, may re-introduce the contaminants of interest to the gut.
Although the soluble forms of the contaminants present may not be affected by
the second passage through the GI tract, any interaction with organic matter and
microbial communities may differ compared to the contaminant bound to the soil.
An animal model considered to be physiologically similar to humans is the pri-
mate, however, few experiments have been conducted with this model (Roberts et al.
2007a ). The reason for this is that this model is expensive and ethically fragile. The
juvenile swine is considered to be a useful anatomical proxy for the human neonatal
digestive tract (Miller and Ullrey 1987 ; Moughan et al. 1992 ) and has been success-
fully used to assess the bioavailability of lead (Casteel et al. 1996 , 2006 ). Further
considerations that determine the choice of animal model include the developmen-
tal speed, intestinal tract aging, the ratio between the bone and body mass etc., to
this end, although rats and rabbits are adequate models, the juvenile swine model
is a preferred candidate (Moughan et al. 1994 ; Rowan et al. 1994 ). Animal stud-
ies are expensive, criticized due to animal welfare and cannot be conducted with a
large enough number and variety of contaminated soils. In-vitro tests (i.e. tests per-
formed in a laboratory dish or test tube; an artificial environment (Latin for in glass ))
allow researchers to overcome limitations of animal tests (Oomen et al. 2003 ; Ruby
2004 ; Ruby et al. 1999 ). However, animal testing still remains a necessary means to
validate in-vitro methods (Schroder et al. 2004b ).
Despite the problems associated with animal testing there are a number of dif-
ferent end-points that can be used to assess relative oral bioavailability. Because of