Issues in Risk Assessment (1993)
Chapter: BACKGROUND
Appendixes
Appendix A
Workshop Summary Maximum Tolerated Dose: Implications For Risk Assessment
INTRODUTION
This report summarizes the discussions at a workshop held by the Committee on Risk Assessment Methodology on September 6, 1990, in Washington, DC. An agenda and a list of presenters, discussants, and other participants are appear in Appendixes D and E.
BACKGROUND
Current testing for carcinogenicity in laboratory animals involves testing both sexes of rats and mice for 2 years (nearly a lifetime) at an estimate of the maximum tolerated dose (MTD) and usually at one or more lower doses. The MTD is defined generally as the highest dose of the test agent that is predicted not to alter the animals' longevity or growth because of noncancer effects. The MTD thus varies inversely with the toxicity of a chemical.
A number of researchers have investigated correlations between the MTD and various measures of carcinogenic potency. Some have concluded that the correlations have a biologic basis and might be indicating something general about mechanisms of carcinogenesis. Others have
