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Development in in vitro toxicology
Authors:J R Fry
Institution:(1) Department of Physiology and Pharmacology, Queen's Medical Centre, Nottingham, UK;(2) Department of Physiology and Pharmacology, Medical School, Queens Medical Centre, NG7 2UH Nottingham, UK
Abstract:There are three principal pressures driving the development of in vitro toxicology: (1) the need for more efficient testing systems to cope with the large number of xenobiotics currently being developed; (2) public pressure to reduce animal experimentation; and (3) a need for a better understanding of the mechanisms of toxicity. Within this, in vitro toxicology is focused on local, systemic, and target-organ toxicity. It is becoming increasingly apparent that a step or decision-tree approach using input of a variety of experimental data (physicochemical properties, biokinetics, cytotoxicity) provides the most efficient system for predicting toxicity. Examples of the use of in vitro toxicity systems for prediction of systemic toxicity and target-organ (liver) toxicity are presented.Originally presented at ECCP 93.
Keywords:Cytotoxicity  Prediction  LD50  MTD  Hepatocytes
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