Risk assessment for possible carcinogens: A critical look

Our overall understanding of mechanisms of toxicology in relation to human disease, with prevention of disease as a major objective, depends in part o n the development of an adequate number of ways to assess risks, both short term and long term. Despite the cost, the long duration of the test, and s ome pitfalls, the long-term animal tests remain, to date, the only reliable assay for possible carcinogens. Recent work has concentrated increasingly on the development of short-term tests to replace the long-term tests. Such a development would be most welcome from several points of view. To date, a variety of approaches have been or are being used. These include (1) acti vation to an alkylating agent with DNA as the most important target, genera ting possible mutations in DNA and DNA damage with or without repair, (2) i nduction of cell proliferation, at least a few cycles, with DNA synthesis a s the major target, again favoring mutations, and (3) decrease in cell-to-c ell communication (gap-junctional intercellular communication) as a suppose d test for promotion. None of these proposed assays are reliable indices fo r possible carcinogenic effects of chemicals or other agents; the scientifi c basis for this negative conclusion is discussed.