Introducing a Forum Series: Approaches for Assessing the Human Carcinogenic Risk of Chemicals

Jay I. Goodman, Associate Editor and Lois D. Lehman-McKeeman, Editor-in-Chief

The Forum Section of Toxicological Sciences is designed to provide readers with discussions and commentaries on relevant and timely issues facing toxicologists and to provide an interface between toxicology and public policy. Over the past several years, Forum articles have covered a wide range of topics including international points of view on the scientific basis of risk assessment, the application of new research tools to toxicological issues and their utility in policy decisions, and the regulatory issues associated with novel ingredients and natural products.

With this issue of the journal, we are pleased to announce a new initiative for the Forum Section. A series of articles with emphasis on a very focused, important, and controversial issue has been developed. The theme selected for this inaugural series is The Best Approach for Assessing the Human Carcinogenic Risk that Chemicals Might Pose. To develop this series, manuscripts have been solicited from scientists from around the world who are recognized for their contributions in cancer research, hazard identification, and risk assessment. The articles are intended to be international in scope, and authors from academic, industrial, and government affiliations have been asked to contribute in order to provide diverse and well-rounded perspectives. The authors were challenged to present their views and experiences on this important issue. In doing so, the goal for these articles is to facilitate communication of ideas, promote international discussion and debate, and provide the opportunity to consider new approaches that might be used in cancer hazard identification and risk assessment. The ultimate goal of the series of articles is to provide a venue in order to enhance the scientific basis for evaluating the cancer risk that chemicals might pose to humans.

Today, the standard method for evaluating the potential carcinogenic activity of a chemical is the two-year bioassay in rodents. This involves lifetime treatment of rats and mice, male and female of each species, with maximum tolerated doses (and one or two lower doses) of the compounds of interest, and determining whether there is an increased tumor incidence above background in any tissue. More recently, additional animal models, particularly transgenic mouse models, have been considered as potential surrogates or replacements to this standard test.

A positive response in a carcinogen bioassay may suggest the potential for deleterious effects on human health and carries with it regulatory, financial, and societal implications for the chemical in question. Considerable research has been directed toward understanding fundamental mechanisms of carcinogenic processes as well as defining specific modes of action for particular chemicals or chemical classes. Furthermore, many other molecular, cellular, and biochemical factors, representing fundamental principles in toxicology, are known to play a role in chemical carcinogenesis. As our understanding of the molecular basis of carcinogenic processes continues to grow, it becomes apparent that a critical, constructive evaluation of the studies used to assess the potential carcinogenic hazard that a chemical might pose is timely.

In its present design, the Forum series on cancer bioassay design and risk assessment will feature articles that begin with the current issue and will be published in successive issues of the journal through early 2005. We believe that the Forum series will be successful if it provides an international perspective on approaches for cancer hazard identification and risk assessment, stimulates discussion among scientific colleagues, and serves as a catalyst to advance research and regulatory efforts in this very important area.

It is our intention to develop additional series of articles in the Forum section addressing relevant topical themes. We welcome your suggestions for new initiatives in this area.