Animal Models in Toxicology

Luc Ferrari ferrari at ctrmed.u-nancy.fr
Thu Feb 15 08:08:10 EST 1996

drjackbud at aol.com (DrJackBud) wrote:

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

>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
I am affraid that peroxysome proliferators are not reductase
inhibitors, but I can make a mistake for some. But originally they
were not.
>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.

>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?
Adressing the quality of an animal as a model for human is not so
easy. Iin some cases one species could be, and not in other cases. The
real problem is that we can not predict before doing the experiments
if one particular species is of relevance for one particular compound.
>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?
It can help to make some (hazardous) prediction in later cases, for
new compounds with similar chemical structures or similar action

The most reliable example is thalidomide, which was toxic
(teratogenic) only in rabbits. At this time no experiment included
this species. Now it is a legal point. If you do not now if the
product could be teratogenic, will you suppress the rabbit experiment?
If you know that similar compounds have been detected as potentially
teratogenic, will you test them ?

These are the questions

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