Caenorhabditis elegans As a Promising Alternative Model for Environmental Chemical Mixture Effect Assessment-A Comparative Study.
Paul Wittkowski,Philip Marx-Stoelting,Norman Violet,Verena Fetz,Franziska Schwarz,Michael Oelgeschläger,Gilbert Schönfelder,Gilbert Schönfelder,Silvia Vogl +8 more
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TLDR
C. elegans may be an appropriate model for mixture toxicity testing at least within a first step to identify and prioritize relevant mixtures for further testing, and well-defined concentration-response relationships provide a very good basis for the prediction of mixture effects.Abstract:
A key challenge of mixture toxicity testing is that a multitude of substances with even more combinations need to be tested in a broad dose range. Consequently testing in rodent bioassays, the current gold standard of toxicity testing, is hardly feasible. High-throughput compatible cell culture systems, however, suffer from limitations with respect to toxicokinetics, tissue interactions, and compensatory mechanisms. Therefore, simple organisms like the nematode Caenorhabditis elegans, combining relevant advantages of complex in vivo and fast in vitro assays might prove highly valuable within a testing strategy for mixtures. To investigate the comparability between results obtained with C. elegans and traditional rodent assays, we used five azole fungicides as well investigated model substances. Our findings suggest that azoles act additively in C. elegans which is in line with previous results in rats. Additionally, we show that toxicokinetics are one important factor for the differences in the relative toxicity of the azoles in both species. Importantly, we also demonstrate that in contrast to most rodent in vivo studies, C. elegans assays provide well-defined concentration-response relationships which are a very good basis for the prediction of mixture effects. We conclude that C. elegans may be an appropriate model for mixture toxicity testing at least within a first step to identify and prioritize relevant mixtures for further testing.read more
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Xenobiotic metabolism and transport in Caenorhabditis elegans
Jessica H. Hartman,Samuel J. Widmayer,Christina M. Bergemann,Dillon E. King,Katherine S. Morton,Riccardo F. Romersi,Laura E. Jameson,Maxwell C.K. Leung,Erik C. Andersen,Stefan Taubert,Joel N. Meyer +10 more
TL;DR: A major, fundamental aspect of toxicological science remains underdeveloped in C. elegans: xenobiotic metabolism and transport processes that are critical to understanding toxicokinetics and toxicodynamics, and extrapolation to other species.
Journal ArticleDOI
Synthesis and characterization of polyethylene terephthalate (PET) precursors and potential degradation products: Toxicity study and application in discovery of novel PETases
Milica Djapovic,Dušan Milivojević,Tatjana Ilic-Tomic,Marija Lješević,Efstratios Nikolaivits,Evangelos Topakas,Veselin Maslak,Jasmina Nikodinovic-Runic +7 more
TL;DR: In this article, 11 compounds belonging to the group of PET precursors and possible degradation products have been comprehensively characterized, including 1-(2-hydroxyethyl)-4-methylterephthalate, ethylene glycol bis(methyl terephthalates), methyl bis(2-Hydroxyethyl terephtahalate), 1, 4-benzenedicarboxylic acid, 1,4-bis[2-methoxycarbonyl)benzoyl]oxy]ethyl ester and methyl tris(
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Caenorhabditis elegans for predictive toxicology
TL;DR: The nematode Caenorhabditis elegans offers great potential to address the need for faster and more reliable testing methods for predictive toxicology, and is likely to prove useful as a complementary tool for early toxicity screening, as well as for the identification of conserved modes of toxic action.
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The "EU chemicals strategy for sustainability" questions regulatory toxicology as we know it: is it all rooted in sound scientific evidence?
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Microplastics and Their Impact on Reproduction—Can we Learn From the C. elegans Model?
TL;DR: The nematode Caenorhabditis elegans is suggested to provide an advantageous high-throughput model system for determining the effect of plastic particles on animal reproduction, using reproductive behavioral end points and cellular readouts.
References
More filters
Journal ArticleDOI
The genetics of caenorhabditis elegans
TL;DR: In this paper, the authors describe methods for the isolation, complementation and mapping of mutants of Caenorhabditis elegans, a small free-living nematode worm.
Journal ArticleDOI
The toxicity of poisons applied jointly1
TL;DR: A quantitative analysis of the toxicity of drugs or poisons applied jointly requires that they be administered at several dosages in mixtures containing fixed proportions of the ingredients, and the presence of synergism is indicated.
Journal ArticleDOI
Transcription regulation and animal diversity
Michael Levine,Robert Tjian +1 more
TL;DR: Comparative genome analyses reveal a surprising constancy in genetic content: vertebrate genomes have only about twice the number of genes that invertebrates have, and the increase is primarily due to the duplication of existing genes rather than the invention of new ones.
Journal ArticleDOI
Can Animal Models of Disease Reliably Inform Human Studies
H. Bart van der Worp,David W. Howells,Emily S. Sena,Emily S. Sena,Michelle J. Porritt,Sarah S J Rewell,Victoria E O'Collins,Malcolm R. Macleod +7 more
TL;DR: H. Bart van der Worp and colleagues discuss the controversies and possibilities of translating the results of animal experiments into human clinical trials and the prospects of doing so in the coming years.
Journal ArticleDOI
Finding function in novel targets: C. elegans as a model organism
TL;DR: This review describes how C. elegans models can be used to advance the understanding of the molecular mechanisms of drug action and disease pathogenesis and how these models are amenable to whole-organism high-throughput compound screens and large-scale target validation.