ABSTRACT
This chapter presents information on designing and implementing preliminary and repeated-dose (subchronic and chronic) toxicity studies and on interpreting results of these studies. Suggested study designs are provided to present an overview of typical studies of various duration in rodent and nonrodent species. A variety of government guidelines and regulations for study design have been published; several of these are summarized in the tables presented in this chapter. Samples of much of the documentation necessary to implement a study in our laboratory, as well as checklists to con˜rm that all appropriate prestudy tasks have been performed, are presented for guidance in the type of information required to initiate a toxicity study. Tables presenting guidelines for many of the logistical and scienti˜c decisions which must be made to select appropriate doses, dose volumes, dosing apparatus, and dose administration procedures summarize several formal and informal “rules” used in our and other laboratories. Formulas and sample calculations are provided for calculating doses, dietary concentrations, and test material requirements. Guidelines for types of clinical signs and their experimental signi˜- cance, as well as historical control values for rodent body weight, and survival in our laboratory, are provided for use in evaluating experimental results and interpreting the data. One particularly useful table summarizes the types of organ weight changes which would be expected as a result of food deprivation and resultant decreases in body weight gain; this is helpful in differentiating truly toxic effects from those which are secondary to decreases in weight gain associated with palatability problems or other causes.
