Animal Models

Anil K Dhiri pathit at pathit.com
Thu Feb 15 19:02:12 EST 1996


DrJackBud wrote:

>
> Someone, anyone - help Whitehead and myself.  There must be a better
> reason for doing toxicological investigations and research other than for
> "regulatory authority demands".  Otherwise, why try to develop models?
>
> Some of you toxicologists surely must have some thoughts that would help
> Whithead and myself???

If may be allowed to throw my tuppence worth here:

1. The preclinical toxicology in drug development is a regulatory requirement. The
key pivotal studies are those specified by authorities and have to be done in a
rodent or a non-rodent species.

As to why they are done in the rat and the beagle? Mainly, I believe due to the
extensive backgound data that has over the time been collected from these two
species and thus allowing one to argue ones case when the test results are not clear
cut. The rat and beagle are thus not true models any more but simply a reference
species and the majority of institutions involved in pre-clinical toxicology for
NCE's simply do not want to change the main test species for the routine tox.
studies in order not to get caught in a position where finding in a new test species
would be difficult to explaing in absence of good background data.

Thus, Whitehead's rservations on the Regulatory perspective are fully justified.

2. Investigative toxicology on the other hand is different "kettle of fish". Here,
my view is that if one is trying to understand mechanism of a finding or
relationship to the human then one should select the best representative model.

Although, in-vitro models can help to provide an understanding of cytotoxicity they
still cannot fully replace the invivo testing. After all,in-vivo the adminstered,
NCE or toxin/toxicant will get metabolised while passing through the liver and the
metabolites may weell be more toxic than the original compound.

Thus unless the "HUMAN" wants to become the prime test species then I believe there
is no alternative for animal experimentation until man can produce the so called
"ANDROID" that pysiologically behaves like man but is deviod of feeling or emotion.

Anil
"A caring veterinary toxicopthologist"

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Dr Anil K Dhiri, DVM, MBiol, CBiol, MBA 
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