Implementation of 3R-principles by Eurofins partner laboratory BSL BIOSERVICE: Determination of in vivo starting dose with in vitro methods

By Hana Hofman-Hüther, BSL BIOSERVICE GmbH (a Eurofins partner laboratory), Germany  hhofman-huether@bioservice.com

The 3Rs: Replacement, Reduction, and Refinement are important from a legal, ethical and scientific standpoint. The implementation of the 3R-principles in toxicology research by encouragement of the development and validation of effective in vitro alternative methods is one of the outmost concerns at BSL BIOSERVICE (a Eurofins partner laboratory).

The starting dose prediction for rodent Acute Oral Systemic Toxicity using BALB/c 3T3 NRU test is one part of this BSL BIOSERVICE strategy. The assay is designed to estimate the starting dose for in vivo acute oral toxicity testing by correlating the IC₅₀ value determined in an in vitro cytotoxicity assay using the BALB/c 3T3 mouse fibroblast cell line with the in vivo LD₅₀value. However, the worldwide acceptance of the in vitro data is not identic. However, in vitro assays results were found to be significantly more predictive for acute lethality in humans (R² = 0.77 to 0.83) than rat and mouse LD₅₀ values (R² = 0.65). A small step forward in the animal free age is the use of in vitro cytotoxicity data to determinate the starting dose for in vivo testing of new chemical substances as a means to reduce the numbers of animals used in LD₅₀ tests. And the next step should be the use of alternative in vitro test battery to generate more-relevant data to evaluate human risks and reduce the time, money, and animals involved in testing.

BSL BIOSERVICE (a Eurofins partner laboratory), realising the challenges in toxicology, is pro-actively including integrated testing strategies in the safety evaluation of chemical, pharmaceutical compounds and is supporting its clients with scientific and economic knowledge and expertise in the field of alternative testing.

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