Cancer Prevention & Control
Evaluation of Strategies to Predict the Carcinogenicity of Chemical Compounds
(Other Undergraduate Student)
Brandt, Marissa (US FDA), Riaz Ahmed, Kausar (US FDA), Brown, Ronald (US FDA)
The safety evaluation of medical devices typically involves an assessment of the genotoxicity using a battery of in vitro (cell-based) and in vivo (animal-based) genotoxicity tests. For example, it is common to perform a battery of genotoxicity tests that includes an in vitro bacterial gene mutation assay, an in vitro mammalian genotoxicity assay, and an in vivo cytogenetics assay. From a public health perspective, these tests are used, in part, to assess the potential for compounds released from the device to have a carcinogenic effect. The goal of this study is to compare the ability of three strategies to predict the results of rodent carcinogenicity studies: Option 1, a full battery of tests that includes in vitro bacterial and mammalian mutagenicity test methods and the in vivo micronucleus test; Option 2, an abbreviated test battery that just includes in vitro tests; and Option 3, an approach that uses experimentally derived in vitro test results and model-derived predictions of the results of the in vivo micronucleus assay. The preliminary results from this study suggest that a strategy that involves the use of in vitro genotoxicity tests alone (Option 2) or in vitro tests plus model-derived estimates of in vivo genotoxicity (Option 3) is able to predict rodent carcinogenicity with either the same or better sensitivity that the widely accepted full test battery that includes in vitro bacterial and mammalian mutagenicity test methods plus the in vivo micronucleus test (Option 1). Although these new proposed strategies for genotoxicity assessment do not currently represent regulatory policy, they do show promise as a way to evaluate the potential carcinogenicity of compounds without the need to perform testing in animals. Use of such an approach should be considered in an overall biocompatibility risk assessment for a medical device, including other available information, such as literature.