Proteomics, i.e. the high throughput separation, display and identification of proteins, has the potential to be a powerful tool in drug development. It could increase the predictability of early drug development and identify non-invasive biomarkers of toxicity or efficacy. This review provides an introduction to modern proteomics, with particular reference to applications in toxicology. A literature search was carried out to identify studies in two broad classes: screening/predictive toxicology, and mechanistic toxicology. The strengths and limitations of current methods and the likely impact of techniques in drug development are also considered. Proteomics can increase the speed and sensitivity of toxicological screening by identifying protein markers of toxicity. Proteomics studies have already provided insights into the mechanisms of action of a wide range of substances, from metals to peroxisome proliferators. Current limitations involving speed of throughput are being overcome by increasing automation and the development of new techniques. The isotope-coded affinity tag (ICAT) method appears particularly promising. The application of proteomics to drug development has given rise to the new field of pharmacoproteomics. New associations between proteins and toxicopathological effects are constantly being identified, and major progress is on the horizon as we move into the post-genomic era.

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Rapid regulatory developments in the area of environmental endocrine disruption present a series of potential problems that are identified and illustrated with examples taken from the recent literature. A list of priorities is provided, including the need for additional epidemiological and wildlife studies, the derivation of a coordinated testing strategy, agreement on the toxicities expected of endocrine disrupting agents, and acceptance that whole animal assays will be uniquely critical in this area of toxicology. The intrinsic difficulty of attempting to simultaneously study all aspects of endocrine disruption indicates the need to reduce the scope of the problem, which can be achieved by first studying toxicities mediated by sex hormone receptors.