1). Fig. 2 is a general scheme, generated as a result of break-out group discussions, on the use of alternative approaches used by different industrial sectors and how they are often used as compounds progress from identification to products, along the development pipeline. Naturally, there are a number of similar approaches
where it is not only ethical to avoid animal testing but it makes good business sense to screen compounds for both efficacy and safety using appropriate non-animal models. The point at which animal tests come into the research and development process may be driven by regulation or Dabrafenib datasheet by the lack of an alternative for the evaluation being undertaken. It should be pointed out that strategies that involve a small number of animals at early stages of development may actually reduce the overall numbers of animal procedures that may have identified a toxicological issue much later in development. Therefore refinement and reduction are often forgotten but still very important steps in the overall 3R target. In all sectors an initial evaluation of new chemicals is often made based on their physicochemical properties, e.g. solubility, logKow P, pH, pKa and molecular weight. Assumptions as to likely corrosive effects can be made if the chemical has an ‘extreme’ pH value (⩾11.5 or ⩽2), especially
if it is to be applied topically (it may be corrosive or a skin or eye irritant, for Epigenetics Compound Library example). In order to screen potentially thousands of compounds, many companies incorporate the use of in silico models (listed in Table 2). As part of a risk assessment of possible systemic toxicity, in addition to the characterization of the hazard, the likely
systemic exposure of the chemical has also to be taken into account. This will differ between industries since pharmaceutical companies usually aim to reach a significant target therapeutic plasma concentration and assess the compound on a risk-to-benefit basis. Since the intended exposure target is potentially Bcl-w high, consideration of the risk-to-benefit is important in the pharmaceutical industry (more so than the chemical or cosmetics industry) and the weight of this ratio may also differ according to the different product types (e.g. cancer therapy versus diabetes). For chemicals industries it is key to assess the likely exposure under occupational conditions. In vitro assays are used by all sectors of industry for safety testing but the need for in vitro models in risk assessment will differ according to the needs of the different industrial sectors and the specific question that needs to be addressed. Appropriate models of varying complexity are often used by different sectors to address specific organ toxicity.