Test Method Development on Neurotoxicity PDF Download
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Author: Per Nylén
Publisher: Nordic Council of Ministers
ISBN: 9789289305310
Category : Health risk assessment
Languages : en
Pages : 188
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Book Description
Author: Per Nylén
Publisher: Nordic Council of Ministers
ISBN: 9789289305310
Category : Health risk assessment
Languages : en
Pages : 188
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Book Description
Author: National Research Council
Publisher: National Academies Press
ISBN: 0309045312
Category : Science
Languages : en
Pages : 167
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Book Description
Scientists agree that exposure to toxic agents in the environment can cause neurological and psychiatric illnesses ranging from headaches and depression to syndromes resembling parkinsonism. It can even result in death at high exposure levels. The emergence of subclinical neurotoxicity-the concept that long-term impairments can escape clinical detection-makes the need for risk assessment even more critical. This volume paves the way toward definitive solutions, presenting the current consensus on risk assessment and environmental toxicants and offering specific recommendations. The book covers: The biologic basis of neurotoxicity. Progress in the application of biologic markers. Reviews of a wide range of in vitro and in vivo testing techniques. The use of surveillance and epidemiology to identify neurotoxic hazards that escape premarket screening. Research needs. This volume will be an important resource for policymakers, health specialists, researchers, and students.
Author: National Research Council
Publisher: National Academies Press
ISBN: 0309040477
Category : Science
Languages : en
Pages : 449
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Book Description
Exposure to toxic chemicalsâ€"in the workplace and at homeâ€"is increasing every day. Human behavior can be affected by such exposure and can give important clues that a person or population is in danger. If we can understand the mechanisms of these changes, we can develop better ways of testing for toxic chemical exposure and, most important, better prevention programs. This volume explores the emerging field of neurobehavioral toxicology and the potential of behavior studies as a noninvasive and economical means for risk assessment and monitoring. Pioneers in this field explore its promise for detecting environmental toxins, protecting us from exposure, and treating those who are exposed.
Author: Jimmy Cheng-Jen Liu
Publisher:
ISBN:
Category : Toxicity testing
Languages : en
Pages : 146
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Book Description
The purpose of this study was to provide an overview of the toxicity testing market, identify those key factors which influence the diffusion of an in vitro neurotoxicity test. Living Cell Technologies Ltd is looking to develop and analyse various business models available to LCT to commercialise the in vitro test by employing SWOT analysis tool. Content analysis methodology was utilised in this study. The increasing recognition by pharmaceutical companies in utilising in vitro system in toxicity testing strategies, due to economic, ethical, scientific reasons, is evident. This has created opportunities for LCT and for other companies in this field. Using Rogers' diffusion of innovation theory, the influences of five major attributes of innovations were examined regarding the in vitro neurotoxicity test adoption among pharmaceutical companies. The attributes identified to be more critical to its diffusion were mainly relative advantage, trialability and complexity. A SWOT analysis is conducted to explore the constraints and possibilities of the three main business models -- providing toxicity testing services, supplying in vitro neurotoxicity test assay kit and out-licensing -- available to commercialise the in vitro test method.
Author: OECD
Publisher: OECD Publishing
ISBN: 9264067396
Category :
Languages : en
Pages : 26
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Book Description
A developmental neurotoxicity study will provide information on the effects of repeated exposure to a substance during in utero and early postnatal development. The test substance is administered daily, generally orally, to mated females (rats are ...
Author: Jungeun Lee
Publisher:
ISBN:
Category :
Languages : en
Pages : 0
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Book Description
Micropollutants in the aquatic environment pose a risk to human and environmental health. Effect-based tools have been applied in environmental monitoring for diverse toxicity endpoints but testing method for neurotoxicity is still limited. The goal of this PhD thesis was to develop and implement high-throughput methods for testing neurotoxicity of typical environmental organic pollutants and mixtures of chemicals extracted from water samples. Neurite outgrowth inhibition and acetylcholinesterase (AChE) inhibition were considered as key neurotoxicity endpoints and human neuroblastoma SH-SY5Y cells were used for both assays. The assays were set up in 384-well plates for high-throughput and repeatable concentration-response assessment. The AChE inhibition assay using purified enzyme has been applied widely, but there has been an issue that natural organic matters such as dissolved organic carbon (DOC) contained in environmental samples can suppress AChE inhibition in the assay. In the cellular assay, AChE inhibition by paraoxon-ethyl was not impacted by DOC up to 68 mgc/L and binary mixtures of paraoxon-ethyl and water extracts showed concentration-additive effects, which indicates no disturbance by DOC and applicability of the cell-based AChE inhibition assay for testing of environmental samples. Chemicals with potential developmental neurotoxicity (DNT) are often hydrophobic. Hydrophobic chemicals can easily intercalate into the cell membrane and provoke effects via nonspecific manner, i.e., baseline toxicity. To investigate whether DNT of chemicals is driven via specific modes of action or merely via baseline toxicity, test chemicals were selected based on their potential DNT from literature or a combination of occurrence data and effects detected in water samples. The effects on neurite outgrowth and cytotoxicity were directly measured in SH-SY5Y cells and the observed effects were compared with predicted baseline cytotoxicity. Since existing prediction models for baseline toxicity had limited application, a prediction model was newly established using a mass balance model based on constant critical membrane concentrations, which can be applied for chemicals of a wide range of hydrophobicity and speciation. When comparing the measured effects in SH-SY5Y with the predicted baseline toxicity, more hydrophobic chemicals tended to trigger toxicity on neurite outgrowth and cell viability via baseline toxicity. The hydrophobic chemicals were still often highly potent while some more hydrophilic chemicals exhibited high specificity but often lower potency. Environmental pollutants with specific modes of action targeting neurite outgrowth were identified by comparing the effects on neurite outgrowth and cytotoxicity. Highly specific effects were observed for two carbamate insecticides, the pharmaceutical mebendazole, the biocide 1,2-benzisothiazolin-3-one, and many other chemicals that were detected in surface water and wastewater treatment plant (WWTP) effluent samples. The two types of water samples were tested in neurite outgrowth assay and the effects on neurite outgrowth were even observed when the samples were diluted by a factor of 5. While overall cytotoxicity was similar between two types of samples, higher toxicity on neurite outgrowth was observed for surface water than WWTP effluent. This led to more specific inhibition of neurite outgrowth by surface water, indicating that higher concentrations of chemicals and/or more potent chemicals acting on neurite outgrowth were contained in the surface water samples. Subsequently, the measured mixture effects were further explained by measured effects of single chemicals and overall, chemicals with high effect potency and/or high occurrence were identified as major mixture effect drivers. While main contributors were different between individual samples for surface water, mebendazole was a dominant contributor for the effects observed in WWTP effluent. The detected chemicals still explained only a small fraction of the measured mixture effects of surface water (up to 4.4%) and WWTP effluent (up to 6.8%). When the two neurotoxicity endpoints were assessed in identical samples, the effects appeared not to be related to each other and both neurotoxicity endpoints were sensitive enough to capture toxicity even when the samples were diluted. The experiments with single chemicals and the applications in case studies demonstrated that both neurotoxicity assays are suitable for environmental monitoring of neurotoxicants. Further testing of various chemicals and environmental mixtures can be useful to identify more effect drivers in the environment. Consideration of more diverse neurotoxicity endpoints would enable more comprehensive assessment of water quality. In the future, these assays have also the potential to be used for human biomonitoring and can be applied to other complex environmental matrices such sediments or biota.
Author: Daniel Stengel
Publisher:
ISBN:
Category :
Languages : en
Pages :
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Book Description
Author: Laurent Boualit
Publisher:
ISBN:
Category :
Languages : en
Pages : 0
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Book Description
Thèse. Géosciences. Environnement. 2023
Author: Lucio G. Costa
Publisher: Humana Press
ISBN: 9781617791710
Category : Medical
Languages : en
Pages : 415
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Book Description
In recent years, the need to develop acceptable alternatives to conventional animal testing for neurotoxicity and developmental neurotoxicity has been increasingly recognized, and much effort is being directed toward the development of alternative models, utilizing mostly mammalian cells in culture but also non-mammalian model systems. In Vitro Neurotoxicology: Methods and Protocols presents a series of cellular, biochemical, and molecular methodological protocols in the area of in vitro neurotoxicology, with an emphasis on mammalian cell culture systems. Opening with a section on methodologies for preparing several cellular systems of variable complexity, amenable for in vitro neurotoxicological studies, the thorough volume continues with coverage of methods to measure cellular death and major mechanisms, methods for assessing mechanisms of nervous system cell toxicity related to impairment of cell signaling, while a final section illustrates additional methods for assessing important nervous system processes such as cell proliferation, neuritogenesis, and synaptogenesis. Written in the highly successful Methods in Molecular BiologyTM series format, chapters include introductions to their respective subjects, lists of the necessary materials and reagents, step-by-step, readily reproducible laboratory protocols, and tips on troubleshooting and avoiding known pitfalls. Comprehensive and cutting-edge, In Vitro Neurotoxicology: Methods and Protocols serves researchers with an interest in assessing or characterizing the potential neurotoxicity of environmental contaminants, drugs, or other chemicals.
Author: Chantra Eskes
Publisher: Springer
ISBN: 3319338269
Category : Medical
Languages : en
Pages : 418
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Book Description
This book provides information on best practices and new thinking regarding the validation of alternative methods for toxicity testing. It covers the validation of experimental and computational methods and integrated approaches to testing and assessment. Validation strategies are discussed for methods employing the latest technologies such as tissue-on-a-chip systems, stem cells and transcriptomics, and for methods derived from pathway-based concepts in toxicology. Validation of Alternative Methods for Toxicity Testing is divided into two sections, in the first, practical insights are given on the state-of-the-art and on approaches that have resulted in successfully validated and accepted alternative methods. The second section focuses on the evolution of validation principles and practice that are necessary to ensure fit-for-purpose validation that has the greatest impact on international regulatory acceptance of alternative methods. In this context validation needs to keep pace with the considerable scientific advancements being made in toxicology, the availability of sophisticated tools and techniques that can be applied in a variety of ways, and the increasing societal and regulatory demands for better safety assessment. This book will be a useful resource for scientists in the field of toxicology, both from industry and academia, developing new test methods, strategies or techniques, as well as Governmental and regulatory authorities interested in understanding the principles and practicalities of validation of alternative methods for toxicity testing.
