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The rat is a very important animal model used in toxicology studies. This chapter describes a brief history of toxicology and animal use, and gives an overview of the use of the rat in pharmacologic testing. The types of toxicology studies that use rats are described, including pharmacokinetic, pharmacodynamic, and biometabolism studies; inhalation studies; acute studies; subchronic/chronic studies; genetic, reproductive, and developmental studies; and neurotoxicology studies. Many important variables in toxicology studies are outlined, including the possible effects of diet, water quality, gut flora, microenvironment, disease status, and environmental enrichment. The chapter concludes with a summary of the 3Rs in toxicology testing and the use of alternatives. A bibliography is included to learn more about the topics presented in the chapter.