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Altern Lab Anim. 2017 Nov;45(5):253-260.

New animal-free concepts and test methods for developmental toxicity and peripheral neurotoxicity.

Author information

1
In Vitro Toxicology and Biomedicine Laboratory, Department of Biology, University of Konstanz, Konstanz, Germany; CAAT-Europe, University of Konstanz, Konstanz, Germany; Konstanz Research School Chemical Biology, Konstanz, Germany; Co-operative Research Training Group on In Vitro Testing of Active Ingredients, Konstanz-Sigmaringen, Germany.

Abstract

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.

PMID:
29112453
[Indexed for MEDLINE]

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