What is the maximum safe dose for a drug based on its cyto-toxicity and dosage?

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I noticed from reading that:

Beagles have a blood brain barrier that is closer to humans than collies
Collies have a notoriously permeable blood brain barrier
So in that regard beagles are better for testing than collies

But what are the upsides and downsides of testing on dogs that are:

jack russel terrier
Huskey
Australian Shepherd
Heeler

and dogs that are a mix of those? For example do huskies also have a notoriously permeable blood brain barrier?
 
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Do you mean that, if the effect of a compound is sensitive to modifications of the compound and/or components of the compound; that as the dose of compound rises, the available compound for treating what you're trying to treat has an inverse relationship to dosage given orally. and that as a result, if you need to have a very HIGH level maintained, you'd need to buffer it, or administer it through other means.

Or were you just referring to a specific drug when you said that and not answering my question, specifically, about what a compound (or components of a compound) being sensitive to modifications meant thanks