Maximum Tolerated Dose
MAXIMUM TOLERATED DOSE
The maximum tolerated dose (MTD) is operationally defined in toxicology as the highest daily dose of a chemical that does not cause overt toxicity in a ninety-day study in laboratory mice or rats. This dose is then used for longer-term safety assessment in the same species, usually lasting two years or a lifetime. The rationale for using the MTD is to maximize the likelihood of detecting any chronic disease effects of a chemical, including cancer. Using higher doses also increases the statistical likelihood of detecting the intrinsic hazards of chemicals.
The MTD is controversial, however, in part because of difficulties in extrapolating findings to more realistic doses, and in extrapolating from animals to humans. Its detractors also point out that subtle physiological changes occur at higher doses that can alter the metabolism and disposition of chemicals in ways that make the findings irrelevant to more realistic dose levels. The MTD has been retained, in part, because its long-term use provides a comparative benchmark for the study of additional chemicals. It is supplemented, however, by parallel studies of lower doses, and by a greater emphasis on predictive approaches dependent upon understanding the underlying mechanisms of chemical toxicity.
Bernard D. Goldstein
(see also: Risk Assessment, Risk Management; Safety Assessment; Toxicology )
Bibliography
National Research Council Committee on Risk Assessment Methodology (1993). Issues in Risk Assessment. Washington, DC: National Academy of Sciences.
Rodricks, J. V.; Starr, T. B.; and Taylor, M. R. (1991). "Evaluating the Safety of Carcinogens in Food—Current Practices and Emerging Developments." Food Drug Cosmetic Law Journal 46(5):513–552.
More From encyclopedia.com
Risk Assessment , Risk Assessment (Public Health)
Risk assessment refers to the process by which the short and long-term adverse consequences to individuals or groups… Toxicology , Toxicology is the scientific study of poisons (toxins). Major topics in toxicology include the detection and chemical analysis of poisons, the study… Chemicals , The general public often construes the word "chemical" to mean a harmful synthetic substance. In fact, however, the term applies to any element or co… Toxic Substances Control Act , The Toxic Substances Control Act (TSCA), enacted by Congress in 1976, gives the U.S. Environmental Protection Agency (EPA) the responsibility for che… Chemical Synthesis , Synthesis, Chemical
Chemical synthesis is the preparation of a compound, usually an organic compound, from easily available or inexpensive commercial… Fumigants , Chemical Warfare
Use of petroleum as a weapon during the Gulf War of 1991-1992
Controls over the use of chemical weapons
Terrorism and chemical weapo…
You Might Also Like
NEARBY TERMS
Maximum Tolerated Dose