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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



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APPENDIX A 79 original typesetting files. Page breaks are true to the original; line lengths, word breaks, heading styles, and other typesetting-specific formatting, however, cannot be About this PDF file: This new digital representation of the original work has been recomposed from XML files created from the original paper book, not from the retained, and some typographic errors may have been accidentally inserted. Please use the print version of this publication as the authoritative version for attribution. 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