STRATEGIC HIERARCHICAL APPROACHES TO ACUTE TOXICITY TESTING

Acute toxicity testing, including testing for irritation and sensitization, traditionally has relied heavily on animal models. While this situation has not yet changed dramatically, new developments and approaches offer opportunities to minimize or ultimately to eliminate altogether the use of animals in specific areas of acute toxicity. The value of a structured approach to toxicological evaluation in skin and eye irritation and contact sensitization is discussed in this report. The general approach is one of undertaking a thorough evaluation of existing knowledge, closely paralleled by consideration of chemical structure-activity relationships, followed by appropriate in vitro testing, or, if there is no alternative, a limited animal study. Then only when absolutely necessary is a standard toxicology assay carried out, often to satisfy regulatory requirements. When ethically acceptable, the strategy may also include studies in humans. If these are done in a thorough manner, they may obviate the need for any animal work and should provide the most relevant toxicological assessment. By use of such a structured approach not only can some or all of the 3Rs be achieved, but data to support alternatives in regulatory toxicology can be generated.