Charting a course for cell culture alternatives to animal testing

Cell culture systems (CCS) are finding increasing use in toxicology. They supplement and amplify existing tests in animals, and play a special role in the iterative process involved in studies of mechanisms of toxic action. The need is stressed for adequate standardization and validation of CCS, and meticulous conduct of tests using such systems. A review of some examples of current work with CCS highlights "designer" CCS, primary systems developed for research on morphological, biochemical, and other aspects of toxic action at particular target sites. An account of the use of CCS in studying the stepwise process of neoplastic transformation focuses on C3H/10T1/2 C18 cells in regard to initiation and promotion. CCS of human origin reveal the anticipated interindividual differences in metabolic characteristics and susceptibility to toxic action. Human CCS, especially primary epidermal keratinocytes, are making important contributions to understanding the actions of dioxins. Reasons for the continuing need for whole animals in toxicology are analyzed, to reveal some strategies by which CCS may prove increasingly successful as replacements.