The Experts below are selected from a list of 1806 Experts worldwide ranked by ideXlab platform

Daniel Krewski - One of the best experts on this subject based on the ideXlab platform.

  • the vision of toxicity testing in the 21st century moving from discussion to action
    Toxicological Sciences, 2010
    Co-Authors: Melvin E. Andersen, Daniel Krewski
    Abstract:

    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.

  • toxicity testing in the 21st century bringing the vision to life
    Toxicological Sciences, 2009
    Co-Authors: Melvin E. Andersen, Daniel Krewski
    Abstract:

    In 2007, the U.S. National Academy of Sciences released a report, Toxicity Testing in the 21st Century: A Vision and a Strategy, that envisions a not-so-distant future in which virtually all routine toxicity testing would be conducted in human cells or cell lines in vitro by evaluating cellular responses in a suite of toxicity pathway assays using high-throughput tests, that could be implemented with robotic assistance. Risk assessment based on results of these types of tests would shift towards the avoidance of significant perturbations of these pathways in exposed human populations. Dose-response modeling of perturbations of pathway function would be organized around computational systems biology models of the circuitry underlying each toxicity pathway. In vitro to in vivo extrapolations would rely on pharmacokinetic models to predict human blood and tissue concentrations under specific exposure conditions. All of the scientific tools needed to affect these changes in toxicity testing practices are either currently available or in an advanced state of development. A broad scientific discussion of this new vision for the future of toxicity testing is needed to motivate a departure from the traditional high dose animal-based Toxicological tests, with its attendant challenges for dose and species extrapolation, towards a new approach more firmly grounded in human biology. The present paper, and invited commentaries on the report that will appear in Toxicological Sciences over the next year, are intended to initiate a dialog to identify challenges in implementing the vision and address obstacles to change.

Melvin E. Andersen - One of the best experts on this subject based on the ideXlab platform.

  • the vision of toxicity testing in the 21st century moving from discussion to action
    Toxicological Sciences, 2010
    Co-Authors: Melvin E. Andersen, Daniel Krewski
    Abstract:

    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.

  • toxicity testing in the 21st century bringing the vision to life
    Toxicological Sciences, 2009
    Co-Authors: Melvin E. Andersen, Daniel Krewski
    Abstract:

    In 2007, the U.S. National Academy of Sciences released a report, Toxicity Testing in the 21st Century: A Vision and a Strategy, that envisions a not-so-distant future in which virtually all routine toxicity testing would be conducted in human cells or cell lines in vitro by evaluating cellular responses in a suite of toxicity pathway assays using high-throughput tests, that could be implemented with robotic assistance. Risk assessment based on results of these types of tests would shift towards the avoidance of significant perturbations of these pathways in exposed human populations. Dose-response modeling of perturbations of pathway function would be organized around computational systems biology models of the circuitry underlying each toxicity pathway. In vitro to in vivo extrapolations would rely on pharmacokinetic models to predict human blood and tissue concentrations under specific exposure conditions. All of the scientific tools needed to affect these changes in toxicity testing practices are either currently available or in an advanced state of development. A broad scientific discussion of this new vision for the future of toxicity testing is needed to motivate a departure from the traditional high dose animal-based Toxicological tests, with its attendant challenges for dose and species extrapolation, towards a new approach more firmly grounded in human biology. The present paper, and invited commentaries on the report that will appear in Toxicological Sciences over the next year, are intended to initiate a dialog to identify challenges in implementing the vision and address obstacles to change.

Gary W Miller - One of the best experts on this subject based on the ideXlab platform.

  • Toxicological Sciences measuring the true impact of the journal
    Toxicological Sciences, 2015
    Co-Authors: Gary W Miller
    Abstract:

    As I complete my first 2 years as the editor of Toxicological Sciences, I wanted to take this opportunity to reflect on the progress we have made and the ongoing challenges we face. I intended to focus on the mission of the journal and our influence on the field. However, during the time I was preparing this editorial, the Thomsom Reuter’s 2015 impact factor was released, and I thought it would be useful to discuss the results and provide my interpretation. Although evaluation of journals is important, I continue to be perplexed at how the enterprise of scholarly publishing has become so hung up on a single metric of journal quality. Thus, this piece will focus on the ways one evaluates the quality of the journal and what we are doing to make Toxicological Sciences as influential as possible.

  • improving reproducibility in toxicology
    Toxicological Sciences, 2014
    Co-Authors: Gary W Miller
    Abstract:

    Over the past few months there has been considerable discussion in scientific circles regarding reproducibility of data, or more specifically, the lack thereof (Nature, 2012, 2013). This is a very serious issue for science, including the discipline of toxicology. The director and deputy director of the National Institutes of Health (NIH) in the United States, Dr Francis Collins and Dr Lawrence Tabek, have outlined several steps that the NIH will be taking to improve reproducibility, including additional review of grant applications and greater access to raw data (Collins and Tabek, 2014). The authors point out that this is not an issue of research misconduct, but rather an issue of carelessness at multiple levels of the scientific enterprise. As a leading outlet of research in the field of toxicology, Toxicological Sciences can and will take steps to improve the reproducibility of the research published in our journal. Most of this discussion has focused on preclinical research related to drug development. Lack of reproducibility can prompt unnecessary research, lead a start up company down a fruitless path, or stall a clinical trial of a promising new drug. Although depriving sick patients of innovative treatments is a major concern for many fields, toxicology has the opposite problem. In studying the adverse actions of environmental chemicals and pharmaceuticals, we are trying to identify potentially dangerous unintended effects and stop them from occurring. As toxicology is attempting to prevent a future injury, illness, or adverse effect, poorly designed and executed studies and a lack of an attention to the detail, i.e., low reproducibility, can result in unnecessary harm to citizens and damage to our planet. Toxicology also plays a major role in establishing guidelines, such as reference doses, no adverse effects levels, and safety margins for thousands of chemicals. The integrity of our field depends on the quality of data used in making those decisions. Toxicology must be a data-driven science not an agendadriven science. This requires self-examination of our own biases in advance and the careful design of experiments that negate or control for these biases. For example, many experiments suffer from confirmation bias. An experimenter thinks something to be true and sets off on a course of study to confirm it. It is better to evoke the spirit of Karl Popper and attempt to disprove what we believe to be true. Efforts to disprove our own hypotheses are often rewarded with the comfort that our intuition was correct and our thinking stands up to challenges. More rarely, and perhaps more excitingly, is when our attempts to disprove our hypotheses succeed. Although initially crushing (“the slaying of a beautiful hypothesis by an ugly fact” Thomas Huxley), the revised hypothesis will be stronger and get us closer to the truth we seek. How many graduate students have actually tried (and I mean really tried) to disprove their dissertation hypotheses? Self-preservation makes such attempts difficult and uncomfortable, but the result of such exercises can be rewarding. Either you demonstrate the soundness of your ideas or you realize that you are basing your future on a weak or tenuous premise and hopefully have time to change course. We should welcome robust debate and challenges to our own research. If an organization requests to see our raw data we should not cower as if under an audit, but welcome the close examination of our scientific process and the results that are obtained. As Toxicological findings can have implications for restrictions, regulations, bans, and economic losses, it is essential that the data be robust and verifiable. Some view the vigorous defense of products by corporations as merely an attempt to protect the bottom line.While this may be amajor motivation, these industries have the right to refute poorly designed studies. In fact, they have the obligation to question the quality of the data that may impact their industries. However, bias does not originate from industry alone. Biases in toxicology can be viewed as a bell-shaped curve. On the tails we have companies so defensive of their products that they are unwilling to examine data that have raised safety concerns about a product, although in most cases there is a genuine effort to make products that contribute to an improved quality of life without inflicting harm on humanity. On the other end of the continuum, we have those who believe that every exogenous or man-made chemical is bad, including vaccines, or the academic scientist on a mission to see a particular compound banned regardless of what the data show. The zealotry from both ends of the curve is harmful to the credibility of the scientific community. Fortunately, most of us are somewhere within a standard deviation or two on either side of the mean, but that does not mean we are free of bias. One of the ways of improving reproducibility is to introduce a bit more noise into the experimental system. It is not uncommon for a laboratory to order 80 animals, split them into four, six

Jose Remacle - One of the best experts on this subject based on the ideXlab platform.

  • stress induced premature senescence as alternative Toxicological method for testing the long term effects of molecules under development in the industry
    Biogerontology, 2000
    Co-Authors: Olivier Toussaint, Patrick Dumont, Jean Francois Dierick, Thierry Pascal, Christophe Frippiat, Florence Chainiaux, Joao Pedro De Magalhaes, Francois Eliaers, Jose Remacle
    Abstract:

    No alternative in vitro method exists fordetecting the potential long-term genotoxic effects ofmolecules at subcytotoxic concentrations, in terms ofdays and weeks after exposure(s) to the moleculetested. A theoretical model of cellular senescence ledto the concept that subcytotoxic stresses under anymolecules at subcytotoxic doses, such as moleculesunder development in the pharmaceutical, cosmetics andfood industry, might lead human fibroblasts into a stateclosely related to in vitro senescence. Thisconcept was then experimentally confirmed invitro: many biomarkers of replicative senescence ofhuman fibroblasts were found 72 h after theirexposure to various kinds of stressors used at non-cytotoxic concentrations. This phenomenon has beentermed stress-induced premature senescence (SIPS).Moreover, proteomics studies have revealed that,besides their effects on the appearance of thebiomarkers of senescence, sublethal stresses under avariety of stressors also lead to long-term specificchanges in the expression level of proteins which arestress-specific. These changes have been coined themolecular scars of stress. The proteins correspondingto these molecular scars may be identified using thelatest developments in mass spectrometry. This modelof stress-induced premature senescence may be appliedto the Toxicological Sciences when testing for thepotential irreversible long-term effects of moleculeson the cell fate.

H Schweinfurth - One of the best experts on this subject based on the ideXlab platform.

  • the reach concept and its impact on Toxicological Sciences
    Toxicology, 2006
    Co-Authors: Jan G Hengstler, Heidi Foth, Regine Kahl, P J Kramer, W Lilienblum, T Schulz, H Schweinfurth
    Abstract:

    Currently, comprehensive Toxicological data are available only for a small percentage of the 30,000 substances produced in volumes of 1-100 tons per year in the EU. Substances with inadequate safety data sets may pose a risk to employees, consumers and the environment. To improve this unsatisfactory situation the European Commission put forward a draft concept that will probably become law in 2006. The acronym of this concept is REACH standing for Registration, Evaluation and Authorization of Chemicals. The aim of REACH is to systematically evaluate the risk of approximately 30,000 chemical substances produced, used or imported in quantities of 1-100 tons per year. From a practical point of view the testing requirements for these chemicals are one of the most important parts of the REACH proposal. The latter progressively increase with the volume of chemical substances, including, e.g. acute, subchronic and chronic toxicity tests. Without doubt REACH will provide an important contribution to health protection for workers and consumers. But perhaps even more importantly, REACH offers an opportunity to optimize and innovate testing strategies for chemicals. Such novel techniques are in particular RNA expression profiling, proteome analysis and metabonomics to describe alterations in gene or protein expressions patterns or in metabolite concentrations in response to toxic stimuli. Promising data have been published indicating that these techniques might identify hepato- or nephrotoxic compounds or even carcinogens differentiating between genotoxic and non-genotoxic substances. However, so far only a relatively small number of selected typical substances with well known toxic mechanisms has been tested. Therefore, the most promising innovative techniques should be optimized and validated by investigating a series of other typical but also untypical substances. In a further step a supplementary research program to REACH should be launched including promising innovative techniques (e.g. genomics, proteomics, metabonomics) but also other alternative methods (e.g. in vitro or QSAR), concentrating on the same substances that have to be tested by conventional animal studies in the mandatory part of REACH. In the present review we summarize key features of REACH, and discuss possibilities for the development of improved techniques and integrated strategies for toxicity testing.

  • withdrawn the reach concept and its impact on Toxicological Sciences
    Toxicology, 2006
    Co-Authors: Jan G Hengstler, Heidi Foth, Regine Kahl, P J Kramer, W Lilienblum, T Schulz, H Schweinfurth
    Abstract:

    J. G. Hengstler*, H. Foth, R. Kahl, P.J. Kramer, W. Lilienblum, T. Schulz, H. Schweinfurth Center for Toxicology, University of Leipzig, Institute of Legal Medicine and Rudolf Boehm Institute of Pharmacology and Toxicology, Haertelstr 16-18, 04107 Leipzig, Germany Institute of Environmental Toxicology, University of Halle, D-06097 Halle/Saale, Germany Institute of Toxicology, Heinrich-Heine-University, PO Box 101007, 40001 Dusseldorf, Germany Institute of Toxicology, Merck KGaA, 64271 Darmstadt, Germany Consultant of Toxicology, Lindenweg 15, D-30966 Hemmingen/Han, Germany Thomas Schulz Bundesinstitut fur Risikobewertung (BfR), Thielallee 88-92, 14195 Berlin, Germany Experimental Toxicology, Schering AG, 13342 Berlin, Germany