Abstract
An important component of the safety assessment of a pharmaceutical or environmental agent is determining if the agent has the potential to increase the risk of cancer in humans. In existing safety assessment paradigms, this concern has primarily been addressed by two-year carcinogenicity studies in both rats and mice (Jacobs and Jacobson-Kram 2004; Huff et al. 1998; International Conference on Harmonization 1995). For pharmaceutical agents, there has been increasing use in recent years of six-month studies in transgenic mice as an alternative to the two-year mouse study (Jacobson-Kram et al. 2004). Despite the extensive use of these models, there remains considerable debate regarding the ability of these studies to predict human risk (Alison, Capen, and Prentice 1994; Jacobs 2005; Cohen 2004). Strategies to improve our ability to predict carcinogenic risk continue to evolve, and several of these focus on predicting carcinogenic outcomes with data from shorter-term studies.
In this month’s edition of the Regulatory Forum, Dr. Sam Cohen, an opinion leader in the area of carcinogenicity assessments, presents his perspective on the ability to predict carcinogenic outcomes from short-term studies using hepatic carcinogenesis as a model. Following Dr. Cohen’s articles are commentaries representing alternative viewpoints: Dr. Gerald Long, whose expertise is in the area of carcinogenicity assessments of pharmaceuticals, and Dr. Ronald Lorentzen, an experienced regulatory scientist in the area of food safety. We hope the readership of Toxicologic Pathology finds these viewpoints of interest, and we invite you to submit additional commentary on this important and controversial area of safety assessment.