ATLA::Alternatives to Laboratory Animals

Volume 31, Number 2

The registry of cytotoxicity: toxicity testing in cell cultures to predict acute toxicity (LD50) and to reduce testing in animals.

Willi Halle

c/o ZEBET at the BfR, Diedersdorfer Weg 1, 12277 Berlin, Germany

Translated by Marlies Halder², Andrew Worth², and Elke Genschow⁴

²European Centre for the Validation of Alternative Methods (ECVAM), Institute for Health & Consumer Protection, European Commission Joint Research Centre, 21020 Ispra (VA), Italy; ⁴ZEBET at the BfR, Diedersdorfer Weg 1, 12277 Berlin, Germany

SUMMARY

This is a translation of a report on the Registry of Cytotoxicity (RC), originally published in German in 1998. The report presented an advanced in vitro method, which can significantly reduce the number of animals needed for the toxicity testing of a broad range of compounds/xenobiotics. With the RC method, it was possible to predict the oral or intravenous acute toxicity (LD50) -- which is a regulatory requirement for newly developed pharmaceuticals and industrial and household chemicals -- from the cytotoxicity data (mean IC50 = IC50_X) obtained with mammalian cells. The RC method can be used before the in vivo test, and it does not pose any additional harm or suffering to laboratory animals. The RC method is of broad practical use: it can be applied, for example, in the pharmaceutical industry or the chemical industry in regulatory testing or in research. It is ready for validation, and could then be incorporated into OECD guidelines, thus reducing the total number of animals needed for regulatory toxicity testing. The RC method is based on the comparison of the IC50_X values and the LD50 values by using linear regression analysis. With the RC method, it was possible to predict, within a predefined dose range, the acute oral LD50 for 252 of 347 xenobiotics, and the intravenous LD50 for rats and/or mice for 117 of 150 xenobiotics. Comparative studies showed that these results are highly reproducible.

Keywords: acute oral toxicity, cell line, cytotoxicity, in vitro toxicity, LD50, mouse toxicity, rat toxicity, registry of toxicity, RTECS