Alternative Animal Models

Abstract In toxicological investigations the decision to utilize an alternative animal model is almost always a matter of exigency, wherein the selection of the test species and experimental system is directed at a particular scientific question to be addressed. As is the case in traditional toxicological research, investigations that employ alternative models are conducted for the ultimate benefit of human health, environmental health, and/or the health and well-being of the test species itself. However, alternative animal models, such as birds, amphibians, and fish, have unique attributes and offer specific advantages that may be difficult or impossible to replicate using conventional mammalian research subjects. Among these qualities are specialized anatomic or physiologic features that may be particularly suited to the investigation of certain toxicologic modes/mechanisms of action, biotransformation and elimination pathways, or exposure routes. Most alternative animal research can be divided into four broad categories that include animal models of human disease, drug discovery and toxicity testing, target animal safety studies, and ecotoxicological testing and environmental monitoring. Special considerations for alternative animal assays include elements of study design and implementation, the potential effects of subclinical disease on experimental outcomes, understanding causes of interspecies variability and results extrapolation, and the progressively shrinking knowledge gap that divides non-mammalian research from conventional mammalian toxicologic pathology.