Animal Models in Toxicology

DrJackBud drjackbud at aol.com
Tue Feb 6 06:07:11 EST 1996

In article <4f5ci8$7eb at soap.news.pipex.net>, p.whitehead at dial.pipex.com
(Paul Whitehead) writes:

>Therefore, an animal model as used in toxicology research is not
>necessarily a good alternative to a human model. 

I presume when you say "human model" you mean HUMANS.  If that is so, then
outside of epimediology, I can't think of any prospective way we can test
toxicity in humans.  Any ideas or can you shed any light of how we might
do this?

>The philosophy now is to demonstrate toxicity in the
>requisite number of species, then prove it can't happen in man :-)

What if humans are the only outlier and all of the animal species behave
one way and humans behave differently?
It has been my sad experience that when I set out to "prove" something by
emperical investigations, I end up, at best, building a circumstantial
case.  Furthermore, testing in a number of species, then testing in man is
a "responsible", "ethical"  or "competent" thing to do; BUT are the
animals "models" or are they merely security checks or tests????  Have the
animals told you anything about humans?  If not, then the only reason to
do anything in animals is for the above stated reasons.  However, if the
animals told you anything about humans, I'm at a loss to identify exactly
what the work in animals told.

>Another well known species specific example is  alpha 2 mu globulin
>nephrocarcinogenicity in male rats. 

This good example you cite, related to gasoline renal carcinogenicity is
getting close to the issues at hand about animal models.  You would likely
say that the rat would not be a good animal model for gasolone
carcinogenicity in humans.  Why???  Well, you'd probably say because the
observation in rats is not seen in humans.  Therin lies the question of a
generic nature "Why?"

>structural or metabolic differences exist between animal models and man. 

What other differences do you feel are important?

Differences are important if they result in different observations in
animals and man.  How about differences that do not affect the
observations in animals and man e.g., one sees the sam endpoint in animals
and man?  When should the line be drawn in "differences"??????

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