6 - Applied Clinical Pathology in Preclinical Toxicology Testing

Abstract

This chapter explores applied clinical pathology in preclinical toxicology testing. Clinical pathology testing is an integral component of evaluation of the toxicologic potential of therapeutic agents, pesticides, and industrial chemicals in laboratory animal species. Clinical pathology results assist in establishing dose-response relationships, mechanisms of toxicity, and provide a link with clinical observations and anatomic pathology findings. Clinical pathology is an important tool for monitoring the onset, course, and severity of toxic insults in preclinical animal models and, thereby helps identify critical end points for monitoring the effects of the test article and/or its metabolites in the intended patient population or the population at risk. This chapter describes the key features of hematology, clinical chemistry, and urinalysis in laboratory animal species with respect to supporting judicious study design and interpretation of results from the clinical pathology component of preclinical toxicology studies. Clinical chemistry tests are performed routinely in toxicology studies and generate information regarding the metabolism of carbohydrates, lipids, and proteins; and the integrity of urinary hepatobiliary, musculoskeletal, cardiovascular, and gastrointestinal systems. The chapter provides a figure to illustrate common causes of increases and decreases in clinical chemistry parameters measured in preclinical toxicology studies.