Strategic considerations in industry's use of in vitro toxicology

Industrial concerns have a legal and ethical responsibility to provide information that allows products to be used safely. Current toxicological practice and legal requirements rely on animal experiments to provide much of this information on safety. Nevertheless, there is a clear role for in vitro methods in the overall development and testing of chemicals. During the early stages of development of a new chemical, in vitro tests provide information used in the selection of appropriate candidates from among the many that may be available. Such use of in vitro tests for screening of chemicals must be preceded by adequate validation. The interpretation of results of screening chemicals requires a detailed knowledge of the sensitivity and specificity of the test and of the structures of the chemicals under test. Once in vivo toxicological data are available, in vitro tests may have a key role in providing an understanding of species differences in toxic responses. Examples of the use of in vitro techniques to improve the specificity of animal studies are given and these include studies of trichloroethylene, di(2-ethylhexyl) phthalate, hexachlorobutadiene and a substituted triazole. In the overall process of risk assessment, extrapolation of animal data to the assessment of human hazard is a prerequisite. In vitro techniques can be used to assess species differences in transdermal absorption. They may also help in assessing quantitative differences in metabolic conversion between species. Examples of the use of in vitro techniques to improve the sensitivity of animal studies include the study of the toxicity of methylene chloride. In vitro techniques have developed rapidly over the last decade. Nevertheless, there is only one category of testing within regulatory guidelines that specifies in vitro methods, namely mutagenicity. At the moment, in vivo methods are considered to provide the best general information for risk assessment, with in vitro methods contributing as screening techniques and as adjuncts to improve the sensitivity and specificity of animal studies.