ABSTRACT

Animal surrogate or cell culture analog (CCA) systems mimic the biochemical response of an animal or human when challenged with a chemical or drug. A true animal surrogate is a device that replicates the circulation, metabolism, or adsorption of a chemical and its metabolites using interconnected multiple compartments to represent key organs. These compartments make use of engineered tissues or cell cultures. Physiologically based pharmacokinetic models (PBPK) guide the design of the device. The animal surrogate, particularly a human surrogate, can provide important insights into toxicity and efficacy of a drug or chemical when it is impractical or imprudent to use living animals (or humans) for testing. The combination of a CCA and PBPK provides a rational basis to relate molecular mechanisms to whole animal response.