ALTERNATIVES IN SAFETY TESTING - PROGRESS OR USELESSNESS

Safety testing is a major responsibility of toxicologists. Toxicology is not only a science but also an art. The science of toxicology chara cterises the toxic potential of a given chemical entity, i.e. the intr insic property which allows it to react with, and/or to be transformed by, a particular biological system. Based on such scientific data, th e art of toxicology has to predict the risk, i.e, the probability that a particular adverse event will occur during a stated period of time or result from a particular challenge. Until now, the science of toxic ology has relied almost exclusively on animal tests, the protocols of which are described in directives and regulations. As stated in an Edi torial in ATLA (1) the question that toxicologists now have to tackle is, ''can non-animal toxicity studies become genuine replacement alter natives...'' for assessing risk adequately? Indeed, the science of tox icology has developed, and continues to develop, new approaches (alter natives) to characterise, in well-defined in vitro models (including, for the first time, human models), the toxic potential of chemicals, n amely, cytotoxicity, organ-specific effects, modulation of metabolic f unctions, interference with cell-mediated processes, metabolic activat ion, etc. But the question remains, what about the art of toxicology? Is it realistic to predict that such new scientific data will, in time , be accepted by regulators for risk evaluation? If these data are to be accepted, we believe that, instead of the present trend towards a r egulation required ''protocol toxicology'', toxicologists will have to impose a stepwise decision-tier approach based on the systematic and sequential progression of scientifically justified and rigorously perf ormed investigations, the results of which will be thoroughly and real istically evaluated by experts. It has to be recognised that scientifi c knowledge has advanced far enough to permit a focus on mechanisms, s o that alternatives are fully accepted, no longer as a supplement to a check-list approach, but as a full part of the scientific expertise.