Animal Models in Toxicology

Paul Whitehead p.whitehead at dial.pipex.com
Mon Feb 5 11:51:38 EST 1996


Hofstra at aa.wl.com (HOFSTRA ANGELA 905-822-3520) wrote:

>I think the question posed by John Budney is an interesting one.  I work on
>peroxisome proliferation, which is essentially a rodent phenomenon.  Although
>it is interesting in itself, the driving force for this research is the
>correlation between peroxisome proliferation and hepatocarcinogenicity in
>rodents and the potential risk to humans.  Peroxisome proliferators include
>plasticizers, hypolipidemics and some NSAIDS, things the average person will
>encounter.  However, humans do not respond to these peroxisome proliferators
>the way rodents do.  So can we really draw any conclusions from rodent work
>about human risk?

Another well known species specific example is  alpha 2 mu globulin
nephrocarcinogenicity in male rats.  Such phenomena will become more
common as researchers delve into the mechanisms of toxicity.  The
increase in mechanistic research results in part from the need to
identify whether such responses are species specific, in order to
decide whether to proceed with, eg drug development.  Toxicologists
are not inclined to accept toxic responses at face value since so many
structural or metabolic differences exist between animal models and
man.  

Therefore, an animal model as used in toxicology research is not
necessarily a good alternative to a human model.  On the other hand a
pharmacological model would be expected to demonstrate a consistent
response to a particular stimuli.  Where is the line drawn between
pharmacology and toxicology?

>Having said that, I do believe that knowledge gained from animal models can be
>applied to the human situation if we keep in mind the differences.

I would say it is absolutely essential to keep in mind the
differences, particularly in view of the limited range of animal
species that can be used.  The concept of using a species that
'closely resembles man' is a non-starter as more and more differences
come to light.  The philosophy now is to demonstrate toxicity in the
requisite number of species, then prove it can't happen in man :-)

 



Paul Whitehead BSc CBiol MIBiol DABT
United Kingdom
e-mail p.whitehead at dial.pipex.com




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