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.