Issues in the design and interpretation of chronic toxicity and carcinogenicity studies in rodents: approaches to dose selection.

For more than three decades chronic studies in rodents have been the benchmark for assessing the potential long-term toxicity, and particularly the carcinogenicity, of chemicals. With doses typically administered for about 2 years (18 months to lifetime), the rodent bioassay has been an integral component of testing protocols for food additives, pesticides, pharmaceuticals, industrial chemicals, and all manner of byproducts and environmental contaminants. Over time, the data from these studies have been used to address an increasing diversity of questions related to the assessment of human health risks, adding complexity to study design and interpretation. An earlier ILSI RSI working group developed a set of principles for the selection of doses for chronic rodent studies (). The present report builds on that work, examining some of the issues that arise and offering new perspectives and approaches for putting the principles into practice. Dose selection is considered both from the prospective viewpoint o...