Use of differential display-polymerase chain reaction to identify genes selectively modulated by chemical allergens in reconstituted human epidermis. Second International Celltox-AICC Joint Meeting "In Vitro Models and Toxicity Mechanisms"

The origins of the concept of replacement alternatives in the 1950s, and the impact of societal changes in the 1960s and 1970s, resulting in stricter controls on animal experimentation from the 1980s, based on the Three Rs of Russell and Burch (reduction, refinement and replacement), are reviewed. The range of replacement alternative methods, and some of the ethical issues they raise, and progress toward their incorporation into fundamental and applied research, education, and, in particular, toxicity testing, are discussed. It is concluded that much greater effort should be put into overcoming the barriers to the acceptance of replacement alternatives, which currently limit the contributions they have to make toward greater humanity and better biomedical science. Particular emphasis is place on the need to ensure that the validation of non-animal tests (for their reliability and relevance for specific purposes) is conducted fairly and objectively, and that greater heed is paid to the warning of Russell and Burch about the high fidelity fallacy and the questionable relevance of data provided by animal models for human hazard and risk assessment. Finally, the role of ECVAM in the promotion of valid replacement alternatives, and the opportunities afforded by the Sixth Amendment to the EC Cosmetics Directive, are discussed.