Genetic toxicology plays a critical role in assessing potential health risks from exposure to xenobiotic agents. This area of toxicology can also help us define critical cellular events that lead to the transformation of an apparently normal somatic cell into a genetically initiated cell with the potential to induce tumors. Short-term in vitro genetic toxicology screening assays have greatly facilitated research activity directed toward the identification of possible genotoxic agents. However, experience with these assays over the last two decades has shown that some chemicals identified in vitro as having genotoxic potential failed to elicit a similar activity in vivo. For obvious reasons, the in vitro systems are limited in many ways in mimicking the fate and biological consequences of the chemical in the whole animal. For this reason, the standard battery of genetic toxicology tests in tier I invariably includes at least one in vivo test. The bone marrow micro-nucleus test is frequently the assay of choice among genetic toxicologists in tier I because of its simplicity. However, there are a number of situations in which the micronucleus test may not be appropriate to address the in vivo genotoxic potential of a material. For example, this assay cannot provide any information on the genotoxicity that occurs only at the portal of entry tissue, such as the gastrointestinal tract after oral administration, the skin in dermal application studies, and the upper respiratory tract in inhalation studies. A number of other in vivo tests complement the results obtained from the basic set of screening tests. The need for these assays and the principles underlying various aspects of the commonly used complementary tests are discussed below.

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