Prevalidation of the ex-vivo model PCLS for prediction of respiratory toxicity

Toxicology in Vitro : an International Journal Published in Association with BIBRA
A HessKatherina Sewald

Abstract

In acute inhalation toxicity studies, animals inhale substances at given concentrations. Without additional information, however, appropriate starting concentrations for in-vivo inhalation studies are difficult to estimate. The goal of this project was the prevalidation of precision-cut lung slices (PCLS) as an ex-vivo alternative to reduce the number of animals used in inhalation toxicity studies. According to internationally agreed principles for Prevalidation Studies, the project was conducted in three independent laboratories. The German BfR provided consultancy in validation principles and independent support with biostatistics. In all laboratories, rat PCLS were prepared and exposed to 5 concentrations of 20 industrial chemicals under submerged culture conditions for 1h. After 23 h post-incubation, toxicity was assessed by measurement of released lactate dehydrogenase and mitochondrial activity. In addition, protein content and pro-inflammatory cytokine IL-1α were measured. For all endpoints IC50 values were calculated if feasible. For each endpoint test acceptance criteria were established. This report provides the final results for all 20 chemicals. More than 900 concentration-response curves were analyzed. Log10[IC50 (...Continue Reading

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Dec 9, 2016·Human Vaccines & Immunotherapeutics·Angela TemannVidadi Yusibov
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Mar 12, 2021·Cardiovascular Research·Fabian Philipp KreutzerThomas Thum
Sep 28, 2021·Molecular Microbiology·Flávia VianaGunnar N Schroeder

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