Comparative analysis of eight cytotoxicity assays evaluated within the ACuteTox project

A comparative analysis of eight cytotoxicity assays [the 3T3 and normal human keratinocytes Neutral Red Uptake (NRU) assay, the primary rat hepatocytes, human HepG2 and 3T3 MTT assay, and the human A.704, SH-SY5Y and HepG2 cells propidium iodide (PI) assay] included in several work packages of the EU Integrated Project ACuteTo x, has been carried out. The aim was to evaluate whether cells origina ting from liver, kidney and brain provided different in vitro acute toxicity results, and the influence of primary liver cells versus cell lines originated from the same tissue. Spearman rank correlation analysis and Hierarc hical Cluster Analysis were performed based on the IC 50 (50% inhibitory concentr ations for the endpoint measured) values generated for 57 chemicals. A relatively large number of neurotoxicants and hepatotoxicants were included which allowed to examine the impact of chemicals with specific tissue toxicity on the results. Our analyses confirmed the similarity between the NRU assays and between the two hepatic cell systems related MTT assays. The type of assay appears to have the greatest influence upon the clustering result regardless of the origin of the cells used. The information provided by the NRU and MTT assays differed from that provided by the PI assay. This approach did not allow to show tissue specific toxicity but it does reveal the effectiveness of the clustering methodology for choosing assays for a testing program for predicting e.g. acute oral toxicity in humans.

CLOTHIER Richard;  GOMEZ-LECHON Maria Jose;  KINSNER-OVASKAINEN Agnieszka;  KOPP-SCHNEIDER Annette;  O'CONNOR Jose Enrique;  PRIETO PERAITA Maria Del Pilar;  STANZEL Sven; 

2013-05-06

PERGAMON-ELSEVIER SCIENCE LTD

JRC66816

0887-2333,   

http://www.sciencedirect.com/science/article/pii/S0887233312002226,    https://publications.jrc.ec.europa.eu/repository/handle/JRC66816,   

10.1016/j.tiv.2012.08.015,