An in vitro approach to the evaluation of repeat exposure in the prediction of toxicity

A strategy for the examination of repeat chronic exposure employed chemicals in the MEIC scheme. Repeat exposure to a non-cytotoxic concentration of certain chemicals leads to changes in sensitivity to a subsequent acute challenge. Six sequential exposures to 3T3-L1 cells, maintained in exponential growth, to ethylene glycol results in an enhanced resistance to cytotoxic damage from a subsequent challenge with 2-propanol. 2-propanol pre-exposure did not alter sensitivity to ethylene glycol. Ethanol or methanol pre-exposure reduces the apparent toxicity to a subsequent challenge with methanol or ethanol. Paracetamol or aspirin pretreatment reduces the toxic effects of paracetamol or aspirin. Hence, repeat exposure can result in a modulation of the cellular responses noted in vitro to cytotoxic concentrations of chemicals. This method demonstrates one approach to examining in vitro the relevance of chronic toxicity in vivo. (C) 1997 Published by Elsevier Science Ltd.