Genetic toxicity testing development

As a Screen. An agent that is positive in one or more genetic toxicity tests may be more likely than one that is negative to be carcinogenic and, therefore, may not warrant further development. 

Then, in the mid 1970s, Professor Bruce Ames of the University of California at Berkeley came along. We discussed in Chapter 5 Professor Ames role in the development of tests for genetic toxicity, tests that tell us something about mechanisms of carcinogenicity. 

LD50 is a measure of acute toxicity. Over time, many other test requirements have been added to establish safety as shown in the safety decision tree developed by the Food Safety Council (1982). In this system an organized sequence of tests is prescribed (see Figure 12-1). Other tests in this system involve genetic toxicity, metabolism, pharmacokinetics (the pathways of chemicals in the system and their possible accumulation in organs), subchronic toxicity, teratogenicity (birth defects), and chronic toxicity. To all this are added tests for carcinogenicity and... 

Although not strictly a genetically engineered mouse model, mice have been developed in which mouse hepatocytes have been replaced by human hepa-tocytes. These mice have been used for metabolism and toxicity testing,65-69 although perhaps their most valuable application is for focused mechanistic in vivo studies. 

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