The European ACuteTox Project: A Modern Integrative In Vitro Approach to Better Prediction of Acute Toxicity

Clemedson, Cecilia

doi:10.1038/clpt.2008.135

Cited by 19 publications

(3 citation statements)

References 6 publications

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“…The core of the ACuteTox project is composed from the generation of a high quality in vivo data base, the generation of a high quality in vitro data base, and the compilation of cell systems and endpoints. In vitro data include those obtained in cytotoxicity assays and in specific in vitro/in silico assays for biokinetics, metabolism and organ toxicity (hepatotoxicity, nephrotoxicity and neurotoxicity) [32]. All this information is stored in a data base that will be publicly available on completion of the project.…”

Section: Introductionmentioning

confidence: 99%

Gene–environment interactions: Neurodegeneration in non-mammals and mammals

Aschner

Levin

Suñol³

et al. 2010

NeuroToxicology

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The understanding of how environmental exposures interact with genetics in central nervous system dysfunction has gained great momentum in the last decade. Seminal findings have been uncovered in both mammalian and non-mammalian model in large result of the extraordinary conservation of both genetic elements and differentiation processes between mammals and non-mammalians. Emerging model organisms, such as the nematode and zebrafish have made it possible to assess the effects of small molecules rapidly, inexpensively, and on a miniaturized scale. By combining the scale and throughput of in vitro screens with the physiological complexity and traditional animal studies, these models are providing relevant information on molecular events in the etiology of neurodegenerative disorders. The utility of these models is largely driven by the functional conservation seen between them and higher organisms, including humans so that knowledge obtained using non-mammalian model systems can often provide a better understanding of equivalent processes, pathways, and mechanisms in man. Understanding the molecular events that trigger neurodegeneration has also greatly relied upon the use of tissue culture models.The purpose of this summary is to provide-state-of-the-art review of recent developments of nonmammalian experimental models and their utility in addressing issues pertinent to neurotoxicity (Caenorhabditis elegans and Danio rerio). The synopses by Aschner and Levin summarize how Publisher's Disclaimer: This is a PDF file of an unedited manuscript that has been accepted for publication. As a service to our customers we are providing this early version of the manuscript. The manuscript will undergo copyediting, typesetting, and review of the resulting proof before it is published in its final citable form. Please note that during the production process errors may be discovered which could affect the content, and all legal disclaimers that apply to the journal pertain. NIH Public Access Author ManuscriptNeurotoxicology. Author manuscript; available in PMC 2011 September 1. C. Elegans as an Alternative Model in Toxicology Caenorhabditis elegans in Neurotoxicology StudiesThe search for experimental models that allow live in vivo analysis in the toxicological field has led to the use of several invertebrate organisms. Caenorhabditis elegans (C. elegans) has demonstrated great advantages in providing insights into the mechanisms of toxicity and neuronal injury. The codification of the complete genome revealed the extraordinary conservation of its genome with mammals (60-80% homology) [1] and studies indicating that worms and mammals share similar biosynthetic and metabolic pathways provide justification for its relevance in the toxicological field.C. elegans has a small size (adults are ~1 mm long), ease of maintenance, ability to be frozen and stored, speedy generation time (3 days), short life span, and large brood size (>300 progeny per hermaphrodite). All these features provide a limitless supply of worms for cell...

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Section: Introductionmentioning

confidence: 99%

Gene–environment interactions: Neurodegeneration in non-mammals and mammals

Aschner

Levin

Suñol³

et al. 2010

NeuroToxicology

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“…An average IC50 for the ten 24-hour human cell line tests predicted peak LCs better (R 2 0.74) than other groups of tests (Ekwall, 1999). This claimed predictivity formed the basis for the A-cute-Tox project (Clemedson, 2008). In this FP6 EU project, the correlation of in vitro cytotoxicity with animal LD50 data and human lethal blood concentrations was further evaluated, and clearly lower correlations were found.…”

Section: Consideration 4: Kinetics Cannot Explain All Organ Selectivimentioning

confidence: 99%

Cellular resilience

Smirnova

Harris

Leist

et al. 2015

ALTEX

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“…In the EU-sponsored project A-cute-tox not only basal cytotoxicity was studied, but also the disturbance of physiological functionality in in vitro systems derived from e.g. the liver, the nervous system and the haematological system (Clemedson, 2008). The increase in insights in toxicological processes was also instrumental in the definition of toxicity pathways (Eisenbrand et al, 2002), in vitro biomarkers of toxicity (Blaauboer et al, 2012), stress response pathways or adverse outcome pathways (Jennings, 2013).…”

mentioning

confidence: 99%

The long and winding road of progress in the use of in vitro data for risk assessment purposes: From “carnation test” to integrated testing strategies

Blaauboer

2015

Toxicology

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The European ACuteTox Project: A Modern Integrative In Vitro Approach to Better Prediction of Acute Toxicity

Cited by 19 publications

References 6 publications

Gene–environment interactions: Neurodegeneration in non-mammals and mammals

Gene–environment interactions: Neurodegeneration in non-mammals and mammals

Cellular resilience

The long and winding road of progress in the use of in vitro data for risk assessment purposes: From “carnation test” to integrated testing strategies

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