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 )
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.
"Maximum Tolerated Dose." Encyclopedia of Public Health. . Encyclopedia.com. (March 19, 2019). https://www.encyclopedia.com/education/encyclopedias-almanacs-transcripts-and-maps/maximum-tolerated-dose
"Maximum Tolerated Dose." Encyclopedia of Public Health. . Retrieved March 19, 2019 from Encyclopedia.com: https://www.encyclopedia.com/education/encyclopedias-almanacs-transcripts-and-maps/maximum-tolerated-dose
Encyclopedia.com gives you the ability to cite reference entries and articles according to common styles from the Modern Language Association (MLA), The Chicago Manual of Style, and the American Psychological Association (APA).
Within the “Cite this article” tool, pick a style to see how all available information looks when formatted according to that style. Then, copy and paste the text into your bibliography or works cited list.
Because each style has its own formatting nuances that evolve over time and not all information is available for every reference entry or article, Encyclopedia.com cannot guarantee each citation it generates. Therefore, it’s best to use Encyclopedia.com citations as a starting point before checking the style against your school or publication’s requirements and the most-recent information available at these sites:
Modern Language Association
The Chicago Manual of Style
American Psychological Association
- Most online reference entries and articles do not have page numbers. Therefore, that information is unavailable for most Encyclopedia.com content. However, the date of retrieval is often important. Refer to each style’s convention regarding the best way to format page numbers and retrieval dates.
- In addition to the MLA, Chicago, and APA styles, your school, university, publication, or institution may have its own requirements for citations. Therefore, be sure to refer to those guidelines when editing your bibliography or works cited list.