I'm doing a bit of research into pre-clinical toxicology methods. Could anybody help me out or point me towards a source of info? The question on my mind is - once those in drug discovery/development have a lead and want to assess its toxicity, how do they decide what are the high/medium/low doses to administer to the animals? Surely there must be some kind of rule of thumb? What about in vitro assays? Is there a rule of thumb that says, for example "x concentration of drug in a primary hepatocyte assay is approx. equivalent to administering x amount of the drug to the animal equivalent"? Should one try and match in vitro concentrations with in vivo blood concentrations? I'm trying to get a feel for how this is all done.

I have posted a reply in the drug discovery section. Do not try to match blood conc - instead look for physiological indicator levels e.g. liver function/ALT/AST levels

for the dose calculation for toxicity studies are starting from the acute toxicity by single dose. on that basis LD50 can be possible and on the base of LD50 further dose to be decided. all this studies are to be experiment on animal and from animal studies human equivalent dose could be possibe to count.
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