CHALLENGES TO DEFAULT ASSUMPTIONS STIMULATE COMPREHENSIVE REALISM AS A NEW TIER IN QUANTITATIVE CANCER RISK ASSESSMENT

The current practice in carcinogen risk assessment of using a lineariz ed multistage model and assuming low-dose linearity is based on severa l false premises. In many cases linearity at low doses would not be ex pected based on the interaction between the multiple components in the carcinogenic process. The two-stage growth models, involving multiple mutations and cell birth and death rates, provide one means of explor ing these interactions. In addition, if carcinogenesis is considered t o be the imbalance between invading substances and defense mechanisms, then the cancer probability depends on how much the substance increas es or decreases the number of defenders or their efficiency as well as increasing or decreasing the number of invaders. Challenges to low-do se linearity and other default assumptions have stimulated the develop ment of new risk assessment methodologies as have the need for more re alistic estimates of risk, better uncertainty characterization, and gr eater utilization of cost-benefit analyses, and other tools for risk m anagement decision making. ''Comprehensive realism'' is an emerging qu antitative weight-of-evidence risk. assessment methodology which is de signed to reflect all of the relevant and available information and th e current state of knowledge about the health risks associated with a substance, (C) 1995 Academic Press, Inc.