Animal Models in Toxicology

DrJackBud drjackbud at aol.com
Wed Feb 14 13:35:48 EST 1996


In article <4220030905021996.A05337.SPVX01.11A22A430F00*@MHS>,
Hofstra at aa.wl.com (HOFSTRA ANGELA 905-822-3520) writes:

>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?
>
>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.
>
>

Perhaps your work will not validate an animal model for human risk
assessment, but it may tell us that we shouldn't be concerned with the
results that emanate from those studies required by regulations or the
maximum tolerated dose studies with these materials.  The MTD approach was
originally developed to determine carcinogenic potential and to compare
the carcinogenic potency among carcinogens.  Now they are the basis of the
daily toxic horror story.  With your type of investigations, you may
effectively put a wet blanket on the unfounded fears.

Take for example the studies on the reductase inhibitors for lowering
blood cholesterol (are these the hypolipidemics to which you refer in your
post?):  Is there a real human cancer risk?  Work similar to that which
you described in your post in which your currently engaged may tell us why
we shouldn't be concerned.  BTW, the current cancer scare of the month is
addressed in JAMA, Januaary 3, 1996-Vol275, pages 67-69.

Of course, if we used the right model in the first place, we wouldn't have
the problem.

More to the universal point as a question to the active and passive
participants of this discussion:

-Is knowing that a particular animal is not a good model for humans
something of value?

or stated in a little different way

-Is knowing how something works (mechanism) in a species which is not a
good model for assessing risk in humans something of value?



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