Sometime we test a drug in vitro for evaluating its anti-apoptotic effect or antibacterial effect and that basis we can calculate the IC50. Now, can we use this information in calculating the approx. LD50 in mice/rat? If no, then how we should proceed for determining the LD50?
Animals are composed of a bazillion of different cells that interact with each other, so if you use one or more different cell type to determine the LD50, you will kill the animal or get a completely different answer (or no answer at all)
Basically, those values have little to do with each other, so you cannot really extrapolate. Going back to your antibacterials or antibiotics example: efficacy might be related from action on a molecular target that is not present (or very different) in mammals. So, how could you extrapolate anything?
Next to that... the concentration in your cell assays is essentially static. Those assays tell nothing about the bioavailability, distribution and metabolism of your compound in vivo. That's by the way one of the multiple reasons why some molecules that are very active in enzymatic or cell-based assays fail to demonstrate good efficacy in vivo! Sure, if your compounds are a real killer for rodent cells or block a vital receptor or process, you can expect toxicity at some point. But translate that into a LD50?
Your concern to know more about the general toxicity of your compound is not actual at that particular moment! You have to do a very long way to ask this question.
yes we can. Use the epa draft formulation which uses balb/c fibroblast or NHK cells for determination of ic50 using sodium dodecyl sulfate as standard. using the regression formula provided, we can derive ld50, which can be used as starting dose for acute toxicity studies. Main reason this was developed is to reduce the number of animals for toxicology studies
I'll point here towards a document from the European commission (year 2010) regarding prediction of acute and chronic toxicity.
http://ihcp.jrc.ec.europa.eu/our_labs/predictive_toxicology/doc/EUR_24639_EN.pdf
I assume the intro paragraph about acute tox summarizes a lot:
Acute toxicity describes the adverse effects caused by either a single exposure to a chemical substance or multiple exposures within 24 hours. The acute lethal dose to 50% of the treated animals (LD50 value) is the basis for the hazard assessment and classification of chemicals and is widely used for regulatory purposes. However, the LD50 value presents some drawbacks when used for QSAR modelling. First, acute toxicity effects may result from a wide spectrum of biokinetic, cellular and molecular events. Converting the complex, whole-body phenomena related to acute toxicity into a
simple number necessarily leads to a loss of information. Second, available data are highly variable, having been generated by different laboratories, protocols, animal species and strains. This undermines the reliability and repeatability of acute toxicity
measurements. These facts complicate the modeling process and may explain why there are relatively few (Q)SAR models and expert systems for predicting oral acute toxicity , in comparison with other endpoints.
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