Stage 1. Hypothesis formulation and testing

Existing data is reviewed and the results interpreted in light of the available information. Based on this review, either (a) a putative mechanism will be proposed and a series of studies designed to test the hypothesis or (b) studies will be suggested to aid in the formulation of a hypothesis.

Stage 2: Develop an in vitro test species model 

Having identified a putative in vivo mechanism in the test species (usually rodent), an in vitro model of the cellular mechanism will be developed. This may comprise a primary cell line or immortalised cell line and / or the development of a non-cell based assay. The aim will be to provide a simple assay that can confirm our hypothesis, and can be used as a primary screen to evaluate the potential of other candidate compounds.

Stage 3: Develop an in vitro human model

An in vitro model using human cells that is equivalent to the in vitro rodent model, is then developed. This is used to confirm whether the mechanism of toxicity is relevant to man or not, to accurately predict the potential human hazard, and to provide an in vitro human screen that can be used to select better compounds based on the hazard to man.