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A measure of tumorigenic potency incorporating dose-response shape.

Meier KL; Bailer AJ; Portier CJ
Biometrics 1993 Sep; 49(3):917-926
The authors consider a measure of carcinogenic potency that attempts to incorporate an estimate of the shape of the dose response curve in addition to estimated dose effects. An analysis was made of 1,577 different data sets on 286 chemicals in the Carcinogenesis Bioassay Program of the National Cancer Institute/National Toxicology Program. These particular data sets demonstrated a statistically significant dose response relationship. The authors recommend the use of a power proportional hazards assumption over the use of a linear proportional hazards assumption as it allows for a wider variety of dose response relationships. The former method permits increasing, sigmoidal curves while the latter can only accommodate curves that are increasing and concave. The type of potency measure used can have a great effect when estimating the potency associated with a low level of risk. This measurement technique has the smallest correlation with the maximum tolerated dose (MTD) of those measures considered, but it is still nontrivially correlated with the MTD. The authors note that, while the MTD does not give direct information concerning a compound's tumorigenicity, it does provide information regarding the toxicity of that compound. The authors caution that measures such as these provide just one indication regarding the potency of a compound. A regulatory decision regarding the potency of a compound would need to also have information concerning mechanisms, toxicokinetics, and epidemiology.
NIOSH-Author; Carcinogens; Risk-analysis; Cancer-rates; Risk-factors; Laboratory-animals; Tumorigenesis; Carcinogenesis; Mathematical-models
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Page last reviewed: October 16, 2020
Content source: National Institute for Occupational Safety and Health Education and Information Division