ATLA 45, 2017

/ATLA 45, 2017

High-throughput Prediction of Nephrotoxicity in Humans

Lit-Hsin Loo and Daniele Zink

The Lush Science Prize 2016 was awarded to Daniele Zink and Lit-Hsin Loo for the interdisciplinary and collaborative work between their research groups in developing alternative methods for the prediction of nephrotoxicity in humans. The collaboration has led to the establishment of a series of pioneering alternative methods for nephrotoxicity prediction, which includes: predictive gene expression markers based on pro-inflammatory responses; predictive in vitro cellular models based on pluripotent stem cell-derived proximal tubular-like cells; and predictive cellular phenotypic markers based on chromatin and cytoskeletal changes. A high-throughput method was established for chemical testing, which is currently being used to predict the potential human nephrotoxicity of ToxCast compounds in collaboration with the US Environmental Protection Agency. Similar high-throughput imaging-based methodologies are currently being developed and adapted by the Zink and Loo groups, to include other human organs and cell types. The ultimate goal is to develop a portfolio of methods accepted for the accurate prediction of human organ-specific toxicity and the consequent replacement of animal experiments.
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New Animal-free Concepts and Test Methods for Developmental Toxicity and Peripheral Neurotoxicity

Marcel Leist

The complex toxicological fields of repeat dose organ toxicity (RDT) and developmental and reproductive toxicity (DART) still require new concepts and approaches to achieve a fully animal-free safety assessment of chemicals. One novel approach is the generation of relevant human cell types from pluripotent stem cells, and the use of such cells for the establishment of phenotypic test methods. Due to their broad endpoints, such tests capture multiple types of toxicants, i.e. they are a readout for the activation of many adverse outcome pathways (AOPs). The 2016 Lush Science Prize was awarded for the development of one such assay, the PeriTox test, which uses human peripheral neurons generated from stem cells. The assay endpoints measure various cell functions, and these give information on the potential neurotoxicity and developmental neurotoxicity hazard of test compounds. The PeriTox test method has a high predictivity and sensitivity for peripheral neurotoxicants, and thus addresses the inherent challenges in pesticide testing and drug development. Data from the test can be obtained quickly and at a relatively high-throughput, and thus, the assay has the potential to replace animal-based safety assessment during early product development or for screening potential environmental toxicants.
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Training and Good Science are the Foundation Stones for Animal Replacement

Kelly S. Davidge and J. Malcolm Wilkinson

Good science, the training of energetic and enthusiastic young researchers, and the experience of industry veterans, will all be needed to drive the implementation and regulatory approval of animal replacement methods in industry
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2017-11-08T13:52:19+00:00 Tags: , , |