IPCS conceptual framework for evaluating a mode of action for chemical carcinogenesis

The International Programme on Chemical Safety (IPCS) is leading an activit y to harmonize approaches to cancer risk assessment as a part of its larger project on the Harmonization of Approaches to the Assessment of Risk from Exposure to Chemicals. Through a series of workshops and the evaluation of case studies, a number of key components of risk assessments relating to ha rmonization were identified: transparency, terminology, weight of evidence, flexibility, and accessibility/communication. A major impediment to harmon ization identified in the consideration of weight of evidence was the evalu ation of mode of action. To address this need, a conceptual framework was d eveloped, based on the general principles involved in considering the chemi cal induction of a specific tumor in animals. This is based partly on the B radford Hill criteria for causality as modified by Faustman et al. (1997) f or developmental toxicity. The framework is described in this paper followe d by a worked example. It is recognized that the framework addresses only o ne stage in the overall characterization of hazard to humans of chemical ca rcinogens. Another important but separate step is the assessment of relevan ce to humans. This is a priority area for future work in this project. (C) 2001 Academic Press.