General Design of Chronic Toxicity Studies Carcinogenesis as a Model

General Design of Chronic Toxicity Studies Carcinogenesis as a Model 

Chemical carcinogens are identified in this type of bioassay as chemicals which cause either an increase in the incidents of tumors or a decrease in the latency period of tumor development. Compounds which decrease the latency period of tumor development without increasing tumor incidence may not be carcinogenic alone but act as cocarcinogens or promoters of tumor development. Cocarcinogens and promoters are thought to be important factors in cancer development in humans, and their identification may thus be important to cancer prevention. The basis for the IRLG recommendations are dis- 

As shown in this table, it would take a sample population, not including controls, of about 1,000 animals to reasonably exclude the possibility that a substance at a given test dose was not producing cancer in 1% of the exposed animals. This level of sensitivity in fact is rarely achieved since laboratory space limitations and economic factors impose practical ceilings on the numbers of animals which can be included in a test. For example, a test conducted in ac- 

Induced Tumor Proportion of Animals. . . with Tumors. . . Approximate Sample Size 

Dose Levels and Prerequisite Subchronic Testing Carcinogenic chemicals generally exhibit a positive dose response relationship. One means, therefore, of circumventing the relative insensitivity of rodent bioassays that is due to the limited numbers of animals on test is to increase the dose levels of the test compound. The rationale is that a compound, which at low concentrations might induce cancer in 0.1% of an exposed human population, at 10 times or 100 times that concentration may produce a detectable increase in tumor incidence (10%) in a test animal population. 

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