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Mark R. Viant - One of the best experts on this subject based on the ideXlab platform.
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A new approach to Toxicity Testing in Daphnia magna: application of high throughput FT-ICR mass spectrometry metabolomics
Metabolomics, 2009Co-Authors: Nadine S. Taylor, Ralf J. M. Weber, Andrew D. Southam, Tristan G. Payne, Olga Hrydziuszko, Theodoros N. Arvanitis, Mark R. ViantAbstract:Currently there is a surge of interest in exploiting toxicogenomics to screen the Toxicity of chemicals, enabling rapid and accurate categorisation into classes of defined mode-of-action (MOA), and prioritising chemicals for further Testing. Direct infusion FT-ICR mass spectrometry-based metabolomics can provide a sensitive and unbiased analysis of metabolites in only 15 mins and therefore has considerable potential for chemical screening. The water flea, Daphnia magna , is an OECD test species and is utilised internationally for Toxicity Testing. However, no metabolomics studies of this species have been reported. Here we optimised and evaluated the effectiveness of FT-ICR mass spectrometry metabolomics for Toxicity Testing in D. magna . We confirmed that high-quality mass spectra can be recorded from as few as 30 neonates (
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a new approach to Toxicity Testing in daphnia magna application of high throughput ft icr mass spectrometry metabolomics
Metabolomics, 2009Co-Authors: Nadine S. Taylor, Ralf J. M. Weber, Andrew D. Southam, Tristan G. Payne, Olga Hrydziuszko, Theodoros N. Arvanitis, Mark R. ViantAbstract:Currently there is a surge of interest in exploiting toxicogenomics to screen the Toxicity of chemicals, enabling rapid and accurate categorisation into classes of defined mode-of-action (MOA), and prioritising chemicals for further Testing. Direct infusion FT-ICR mass spectrometry-based metabolomics can provide a sensitive and unbiased analysis of metabolites in only 15 mins and therefore has considerable potential for chemical screening. The water flea, Daphnia magna, is an OECD test species and is utilised internationally for Toxicity Testing. However, no metabolomics studies of this species have been reported. Here we optimised and evaluated the effectiveness of FT-ICR mass spectrometry metabolomics for Toxicity Testing in D. magna. We confirmed that high-quality mass spectra can be recorded from as few as 30 neonates (<24 h old; 224 μg dry mass) or a single adult daphnid (301 μg dry mass). An OECD 24 h acute Toxicity test was conducted with neonates at copper concentrations of 0, 5, 10, 25, 50 μg l−1. A total of 5447 unique peaks were detected reproducibly, of which 4768 were assigned at least one empirical formula and 1017 were putatively identified based upon accurate mass measurements. Significant copper-induced changes to the daphnid metabolome, consistent with the documented MOA of copper, were detected thereby validating the approach. In addition, N-acetylspermidine was putatively identified as a novel biomarker of copper Toxicity. Collectively, our results highlight the excellent sensitivity, reproducibility and mass accuracy of FT-ICR mass spectrometry, and provide strong evidence for its applicability to high-throughput screening of chemical Toxicity in D. magna.
Nadine S. Taylor - One of the best experts on this subject based on the ideXlab platform.
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A new approach to Toxicity Testing in Daphnia magna: application of high throughput FT-ICR mass spectrometry metabolomics
Metabolomics, 2009Co-Authors: Nadine S. Taylor, Ralf J. M. Weber, Andrew D. Southam, Tristan G. Payne, Olga Hrydziuszko, Theodoros N. Arvanitis, Mark R. ViantAbstract:Currently there is a surge of interest in exploiting toxicogenomics to screen the Toxicity of chemicals, enabling rapid and accurate categorisation into classes of defined mode-of-action (MOA), and prioritising chemicals for further Testing. Direct infusion FT-ICR mass spectrometry-based metabolomics can provide a sensitive and unbiased analysis of metabolites in only 15 mins and therefore has considerable potential for chemical screening. The water flea, Daphnia magna , is an OECD test species and is utilised internationally for Toxicity Testing. However, no metabolomics studies of this species have been reported. Here we optimised and evaluated the effectiveness of FT-ICR mass spectrometry metabolomics for Toxicity Testing in D. magna . We confirmed that high-quality mass spectra can be recorded from as few as 30 neonates (
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a new approach to Toxicity Testing in daphnia magna application of high throughput ft icr mass spectrometry metabolomics
Metabolomics, 2009Co-Authors: Nadine S. Taylor, Ralf J. M. Weber, Andrew D. Southam, Tristan G. Payne, Olga Hrydziuszko, Theodoros N. Arvanitis, Mark R. ViantAbstract:Currently there is a surge of interest in exploiting toxicogenomics to screen the Toxicity of chemicals, enabling rapid and accurate categorisation into classes of defined mode-of-action (MOA), and prioritising chemicals for further Testing. Direct infusion FT-ICR mass spectrometry-based metabolomics can provide a sensitive and unbiased analysis of metabolites in only 15 mins and therefore has considerable potential for chemical screening. The water flea, Daphnia magna, is an OECD test species and is utilised internationally for Toxicity Testing. However, no metabolomics studies of this species have been reported. Here we optimised and evaluated the effectiveness of FT-ICR mass spectrometry metabolomics for Toxicity Testing in D. magna. We confirmed that high-quality mass spectra can be recorded from as few as 30 neonates (<24 h old; 224 μg dry mass) or a single adult daphnid (301 μg dry mass). An OECD 24 h acute Toxicity test was conducted with neonates at copper concentrations of 0, 5, 10, 25, 50 μg l−1. A total of 5447 unique peaks were detected reproducibly, of which 4768 were assigned at least one empirical formula and 1017 were putatively identified based upon accurate mass measurements. Significant copper-induced changes to the daphnid metabolome, consistent with the documented MOA of copper, were detected thereby validating the approach. In addition, N-acetylspermidine was putatively identified as a novel biomarker of copper Toxicity. Collectively, our results highlight the excellent sensitivity, reproducibility and mass accuracy of FT-ICR mass spectrometry, and provide strong evidence for its applicability to high-throughput screening of chemical Toxicity in D. magna.
Daniel Krewski - One of the best experts on this subject based on the ideXlab platform.
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New Directions in Toxicity Testing
Annual review of public health, 2011Co-Authors: Daniel Krewski, Margit Westphal, Mustafa Al-zoughool, Maxine C. Croteau, Melvin E. AndersenAbstract:In 2007, the U.S. National Research Council (NRC) published a groundbreaking report entitled Toxicity Testing in the 21st Century: A Vision and a Strategy. The purpose of this report was to develop a long-range strategic plan to update and advance the way environmental agents are tested for Toxicity. The vision focused on the identification of critical perturbations of Toxicity pathways that lead to adverse human health outcomes using modern scientific tools and technologies. This review describes how emerging scientific methods will move the NRC vision forward and improve the manner in which the potential health risks associated with exposure to environmental agents are assessed. The new paradigm for Toxicity Testing is compatible with the widely used four-stage risk assessment framework originally proposed by the NRC in 1983 in the so-called Red Book. The Nrf2 antioxidant pathway provides a detailed example of how relevant pathway perturbations will be identified within the context of the new NRC vision for the future of Toxicity Testing. The implications of the NRC vision for Toxicity Testing for regulatory risk assessment are also discussed.
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the vision of Toxicity Testing in the 21st century moving from discussion to action
Toxicological Sciences, 2010Co-Authors: Melvin E. Andersen, Daniel KrewskiAbstract:Over the past year, a series on commentaries have appeared in the Toxicological Sciences Forum Series related to the 2007 National Research Council (NRC) publication, Toxicity Testing in the 21st Century: A Vision and A Strategy. The first article in the series provided an overview of the vision and was accompanied by an editorial by the three editors of Toxicological Sciences. During the past year, eight invited commentaries from the academic, industrial, and regulatory sectors have provided diverse perspectives on the vision, noted challenges to its implementation, and highlighted aspects of Toxicity Testing that were not addressed in the original NRC report. Here, we offer a summary of the main points raised by the commentators in tabular form, identify a number of common themes, and finish the series by providing our perspective on several key issues in charting the path forward to move from discussion to action.
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The Future of Toxicity Testing
Journal of toxicology and environmental health. Part B Critical reviews, 2010Co-Authors: Melvin E. Andersen, Margit Westphal, Mustafa Al-zoughool, Maxine C. Croteau, Daniel KrewskiAbstract:In 2007, the U.S. National Research Council (NRC) released a report, “Toxicity Testing in the 21st Century: A Vision and a Strategy,” that proposes a paradigm shift for Toxicity Testing of environmental agents. The vision is based on the notion that exposure to environmental agents leads to adverse health outcomes through the perturbation of Toxicity pathways that are operative in humans. Implementation of the NRC vision will involve a fundamental change in the assessment of Toxicity of environmental agents, moving away from adverse health outcomes observed in experimental animals to the identification of critical perturbations of Toxicity pathways. Pathway perturbations will be identified using in vitro assays and quantified for dose response using methods in computational toxicology and other recent scientific advances in basic biology. Implementation of the NRC vision will require a major research effort, not unlike that required to successfully map the human genome, extending over 10 to 20 years, invo...
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Toxicity Testing IN THE 21ST CENTURY: A VISION AND A STRATEGY
Journal of toxicology and environmental health. Part B Critical reviews, 2010Co-Authors: Daniel Krewski, Melvin E. Andersen, Kim Boekelheide, Daniel Acosta, Henry A. Anderson, John C. Bailar, Robert L. Brent, Gail Charnley, Vivian G. Cheung, Sidney GreenAbstract:With the release of the landmark report Toxicity Testing in the 21st Century: A Vision and a Strategy, the U.S. National Academy of Sciences, in 2007, precipitated a major change in the way Toxicity Testing is conducted. It envisions increased efficiency in Toxicity Testing and decreased animal usage by transitioning from current expensive and lengthy in vivo Testing with qualitative endpoints to in vitro Toxicity pathway assays on human cells or cell lines using robotic high-throughput screening with mechanistic quantitative parameters. Risk assessment in the exposed human population would focus on avoiding significant perturbations in these Toxicity pathways. Computational systems biology models would be implemented to determine the dose-response models of perturbations of pathway function. Extrapolation of in vitro results to in vivo human blood and tissue concentrations would be based on pharmacokinetic models for the given exposure condition. This practice would enhance human relevance of test result...
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Toxicity Testing in the 21st century implications for human health risk assessment
Risk Analysis, 2009Co-Authors: Daniel Krewski, Melvin E. Andersen, Ellen Mantus, Lauren ZeiseAbstract:At the request of the Environmental Protection Agency, the National Research Council (NRC) recently completed a major report entitled Toxicity Testing in the 21st Century: A Vision and a Strategy. The terms of reference for this report were to develop a long-range vision and strategic plan to advance the practices of Toxicity Testing and human health assessment of environmental agents. The report describes how current and anticipated scientific advances can be expected to transform Toxicity Testing to permit broader coverage of the universe of potentially toxic chemicals to which humans may be exposed, using more timely and more cost-effective methods for Toxicity Testing. The report envisages greatly expanded use of high- and medium-throughput in vitro screening assays, computational toxicology, and systems biology, along with other emerging high-content Testing methodologies, such as functional genomics and transcriptomics. When fully implemented, the vision will transform the ways Toxicity Testing and chemical risk assessment are conducted, moving away from measuring apical health endpoints in experimental animals toward identification of significant perturbations of Toxicity pathways using in vitro tests in human cells and cell lines. Population-based studies incorporating relevant biomarkers will also be useful in identifying pathway perturbations directly in humans and in interpreting the results of in vitro tests in the context of human health risk assessment. The present article summarizes and extends the NRC report and examines its implications for risk assessment practice.
Theodoros N. Arvanitis - One of the best experts on this subject based on the ideXlab platform.
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A new approach to Toxicity Testing in Daphnia magna: application of high throughput FT-ICR mass spectrometry metabolomics
Metabolomics, 2009Co-Authors: Nadine S. Taylor, Ralf J. M. Weber, Andrew D. Southam, Tristan G. Payne, Olga Hrydziuszko, Theodoros N. Arvanitis, Mark R. ViantAbstract:Currently there is a surge of interest in exploiting toxicogenomics to screen the Toxicity of chemicals, enabling rapid and accurate categorisation into classes of defined mode-of-action (MOA), and prioritising chemicals for further Testing. Direct infusion FT-ICR mass spectrometry-based metabolomics can provide a sensitive and unbiased analysis of metabolites in only 15 mins and therefore has considerable potential for chemical screening. The water flea, Daphnia magna , is an OECD test species and is utilised internationally for Toxicity Testing. However, no metabolomics studies of this species have been reported. Here we optimised and evaluated the effectiveness of FT-ICR mass spectrometry metabolomics for Toxicity Testing in D. magna . We confirmed that high-quality mass spectra can be recorded from as few as 30 neonates (
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a new approach to Toxicity Testing in daphnia magna application of high throughput ft icr mass spectrometry metabolomics
Metabolomics, 2009Co-Authors: Nadine S. Taylor, Ralf J. M. Weber, Andrew D. Southam, Tristan G. Payne, Olga Hrydziuszko, Theodoros N. Arvanitis, Mark R. ViantAbstract:Currently there is a surge of interest in exploiting toxicogenomics to screen the Toxicity of chemicals, enabling rapid and accurate categorisation into classes of defined mode-of-action (MOA), and prioritising chemicals for further Testing. Direct infusion FT-ICR mass spectrometry-based metabolomics can provide a sensitive and unbiased analysis of metabolites in only 15 mins and therefore has considerable potential for chemical screening. The water flea, Daphnia magna, is an OECD test species and is utilised internationally for Toxicity Testing. However, no metabolomics studies of this species have been reported. Here we optimised and evaluated the effectiveness of FT-ICR mass spectrometry metabolomics for Toxicity Testing in D. magna. We confirmed that high-quality mass spectra can be recorded from as few as 30 neonates (<24 h old; 224 μg dry mass) or a single adult daphnid (301 μg dry mass). An OECD 24 h acute Toxicity test was conducted with neonates at copper concentrations of 0, 5, 10, 25, 50 μg l−1. A total of 5447 unique peaks were detected reproducibly, of which 4768 were assigned at least one empirical formula and 1017 were putatively identified based upon accurate mass measurements. Significant copper-induced changes to the daphnid metabolome, consistent with the documented MOA of copper, were detected thereby validating the approach. In addition, N-acetylspermidine was putatively identified as a novel biomarker of copper Toxicity. Collectively, our results highlight the excellent sensitivity, reproducibility and mass accuracy of FT-ICR mass spectrometry, and provide strong evidence for its applicability to high-throughput screening of chemical Toxicity in D. magna.
Olga Hrydziuszko - One of the best experts on this subject based on the ideXlab platform.
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A new approach to Toxicity Testing in Daphnia magna: application of high throughput FT-ICR mass spectrometry metabolomics
Metabolomics, 2009Co-Authors: Nadine S. Taylor, Ralf J. M. Weber, Andrew D. Southam, Tristan G. Payne, Olga Hrydziuszko, Theodoros N. Arvanitis, Mark R. ViantAbstract:Currently there is a surge of interest in exploiting toxicogenomics to screen the Toxicity of chemicals, enabling rapid and accurate categorisation into classes of defined mode-of-action (MOA), and prioritising chemicals for further Testing. Direct infusion FT-ICR mass spectrometry-based metabolomics can provide a sensitive and unbiased analysis of metabolites in only 15 mins and therefore has considerable potential for chemical screening. The water flea, Daphnia magna , is an OECD test species and is utilised internationally for Toxicity Testing. However, no metabolomics studies of this species have been reported. Here we optimised and evaluated the effectiveness of FT-ICR mass spectrometry metabolomics for Toxicity Testing in D. magna . We confirmed that high-quality mass spectra can be recorded from as few as 30 neonates (
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a new approach to Toxicity Testing in daphnia magna application of high throughput ft icr mass spectrometry metabolomics
Metabolomics, 2009Co-Authors: Nadine S. Taylor, Ralf J. M. Weber, Andrew D. Southam, Tristan G. Payne, Olga Hrydziuszko, Theodoros N. Arvanitis, Mark R. ViantAbstract:Currently there is a surge of interest in exploiting toxicogenomics to screen the Toxicity of chemicals, enabling rapid and accurate categorisation into classes of defined mode-of-action (MOA), and prioritising chemicals for further Testing. Direct infusion FT-ICR mass spectrometry-based metabolomics can provide a sensitive and unbiased analysis of metabolites in only 15 mins and therefore has considerable potential for chemical screening. The water flea, Daphnia magna, is an OECD test species and is utilised internationally for Toxicity Testing. However, no metabolomics studies of this species have been reported. Here we optimised and evaluated the effectiveness of FT-ICR mass spectrometry metabolomics for Toxicity Testing in D. magna. We confirmed that high-quality mass spectra can be recorded from as few as 30 neonates (<24 h old; 224 μg dry mass) or a single adult daphnid (301 μg dry mass). An OECD 24 h acute Toxicity test was conducted with neonates at copper concentrations of 0, 5, 10, 25, 50 μg l−1. A total of 5447 unique peaks were detected reproducibly, of which 4768 were assigned at least one empirical formula and 1017 were putatively identified based upon accurate mass measurements. Significant copper-induced changes to the daphnid metabolome, consistent with the documented MOA of copper, were detected thereby validating the approach. In addition, N-acetylspermidine was putatively identified as a novel biomarker of copper Toxicity. Collectively, our results highlight the excellent sensitivity, reproducibility and mass accuracy of FT-ICR mass spectrometry, and provide strong evidence for its applicability to high-throughput screening of chemical Toxicity in D. magna.