Title: Evaluation of aggregating brain cell cultures for the detection of acute organ-specific toxicity
Citation: TOXICOLOGY IN VITRO vol. 27 no. 4 p. 1416–1424
Publication Year: 2013
JRC N°: JRC67196
ISSN: 0887-2333
URI: http://www.sciencedirect.com/science/article/pii/S0887233312002007
DOI: 10.1016/j.tiv.2012.06.018
Type: Articles in periodicals and books
Abstract: As part of the ACuteTox project aimed at the development of non-animal testing strategies for predicting human acute oral toxicity, aggregating brain cell cultures (AGGR) were examined for their capability to detect organ-specific toxicity. Previous multicenter evaluations of in vitro cytotoxicity showed that some 20% of the tested chemicals exhibited significantly lower in vitro toxicity as expected from in vivo toxicity data. This was supposed to be due to toxicity at supracellular (organ or system) levels. To examine the capability of AGGR to alert for potential organ-specific toxicant s, concentration–response studies were carried out in AGGR for 86 chemicals, taking as endpoints the mRNA expression levels of four selected genes. The lowest observed effect concentration (LOEC) determined for each chemical was compared with the IC 20 reported for the 3T3/NRU cytotoxicity assay. A LOEC lower than IC 20 by at least a factor of 5 was taken to alert for organ-specific toxicity. The results showed that the frequency of alerts increased with the level of toxicity observ ed in AGGR. Among the chemicals identified as alert were many comp ounds known for their organ-specific toxicity. These findings suggest that AGGR are suitable for the detection of organ-specific toxicity and that they could, in conjunction with the 3T3/NRU cytotoxicity assay, improve the predictive capacity of in vitro toxicity testing.
JRC Directorate:Institute for Health and Consumer Protection Historical Collection

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