Preface Free

Toxicity testing is performed to assess the safety or hazards presented by substances such as industrial chemicals, consumer products, and pharmaceuticals. Many of the test methods currently employed for this purpose use laboratory animals (e.g., mice, rats, or rabbits). Alternative test methods are procedures that, reduce, refine, or replace animals in regulatory toxicity testing. Test methods that can accurately detect whether chemicals and products cause injury or disease are vital to health protection. Improved prevention of injury and disease requires effective translation of new knowledge into better test methods. New test methods should not only be more predictive but also faster, cheaper, and ideally, should minimize the use of animals. Where animals are still considered necessary, new test methods should not only minimize animal use, but also minimize pain and distress. In recent years, increasing emphasis has been placed on identifying promising test methods that use human cell-based technologies to predict responses in humans, typically the species of interest in toxicology testing.

New regulatory safety test methods must protect public health and the environment, performing as well or better than currently accepted methods. For this reason, test method validation must demonstrate that an alternative test method is both scientifically valid and as protective as currently accepted methods. In this text, readers will see that scientists have succeeded in developing alternatives for virtually every toxicity endpoint required for regulatory testing. Alternatives are now available that reduce or even eliminate the need for animals for certain acute endpoints. Likewise, methods are available to address some of the mechanisms associated with longer term and complex processes (e.g., carcinogenicity, reproductive toxicity, and developmental toxicity), but none can account for them all. Therefore, integrated testing strategies are being developed that will allow for a broader assessment of the many mechanisms involved in these complex processes.

In this text, we describe the ever-expanding “toolbox” of test methods available to the toxicologist to determine the hazards associated with test materials of interest. Development of such methods has often resulted from basic science advances that facilitate identification of biochemical and cellular pathways that mediate mechanisms of toxicity. This permits the toxicologist to perform evaluations based on specific information generated in several different methods to generate a so-called “weight of evidence”. By combining in silico, in vitro, and ex vivo methods, coupled with state-of-the-art mid- and high-throughput technologies that rely almost completely on biochemical- and cell-based in vitro assays, toxicologists are moving closer to using mechanistically based alternatives without requiring the use of live animals.

David G. Allen and Michael Waters