Toxicological risk assessment and multi-system health impacts from exposure /

Detalles Bibliográficos
Clasificación:Libro Electrónico
Otros Autores: Tsatsakis, Aristidis M.
Formato: Electrónico eBook
Idioma:Inglés
Publicado: London : Academic Press, 2021.
Temas:
Environmental toxicology.
Hazardous substances > Risk assessment.
Ecotoxicology
�Ecotoxicologie.
Environmental toxicology
Hazardous substances > Risk assessment
Acceso en línea:Texto completo
Tabla de Contenidos:
  • Front Cover
  • Toxicological Risk Assessment and Multi-System Health Impacts From Exposure
  • Copyright Page
  • Contents
  • List of contributors
  • About the editor
  • Preface
  • Endorsements
  • 1 Modern tools and concepts in toxicology testing
  • 1 Mixture toxicity evaluation in modern toxicology
  • 1.1 Introduction
  • 1.2 Real-life exposure scenarios
  • 1.3 Current framework regarding mixture evaluation
  • 1.4 A new methodology for studying toxicity under real-life exposure scenarios
  • 1.5 Key examples of studies supporting the new proposed methodology
  • 1.6 Challenges and further steps
  • 1.7 Conclusions
  • References
  • 2 Alternative methods to animal experimentation and their role in modern toxicology
  • 2.1 Introduction
  • 2.2 Need for validated alternative methods
  • 2.3 International organizations and validation centers: their role in implementating alternative methods into modern toxicology
  • 2.4 Alternative methods development and implementation in the 21st century
  • 2.4.1 Integrated approaches to testing and assessment
  • 2.4.2 Emerging disruptive technologies in the 21st century
  • 2.4.2.1 Dynamic human-on-a-chip systems
  • 2.4.2.2 3D Bioprinting
  • 2.4.2.3 Innovative computational methods
  • 2.4.3 Application of NAMS and mechanistic data for risk assessment under the real-life risk simulation approach
  • 2.5 Strengthening international harmonization and cooperation on the validation and implementation of alternative methods
  • 2.6 Conclusion
  • References
  • 3 The exposome-a new paradigm for non-animal toxicology and integrated risk assessment
  • 3.1 Introduction
  • 3.2 Advancing the toxicological paradigm through exposome
  • 3.2.1 Main concept
  • 3.2.2 Steps toward the implementation of the exposome paradigm in toxicology
  • 3.2.3 Main implications toward modern and pathway-based risk assessment.
  • 3.3 Key advances proposed by the exposome paradigm in toxicology
  • References
  • 4 In silico toxicology, a robust approach for decision-making in the context of next-generation risk assessment
  • 4.1 Introduction
  • 4.2 Relevance and applicability domain of in silico methods
  • 4.3 In silico computational methods for predictive toxicology of chemicals
  • 4.3.1 Structurally based models
  • 4.3.1.1 Structural alerts
  • 4.3.1.2 Quantitative structure activity relationships modeling
  • 4.3.1.3 Rule-based modeling methods
  • 4.3.1.4 Chemical category approaches
  • 4.3.1.5 Virtual screening
  • 4.3.1.5.1 Molecular docking
  • 4.3.1.5.2 Molecular dynamics
  • 4.3.1.5.3 Pharmacophore-based virtual screening
  • 4.3.2 Biologically based models
  • 4.3.2.1 Dose- and time-response models
  • 4.3.2.2 Physiologically based kinetic/dynamic modeling
  • 4.3.2.3 Biologically based dose-response models
  • 4.3.2.4 Quantitative adverse outcome pathways
  • 4.3.3 Read-across
  • 4.4 Application of in silico methods in regulatory science
  • 4.4.1 Use of in silico approaches for risk assessment
  • 4.4.2 Integration of in silico with other new approach methodologies for a mechanistic understanding of chemical-perturbed ...
  • 4.4.3 In silico prediction of reference points
  • 4.4.4 Risk assessment of chemical mixtures
  • 4.5 Conclusions and future directions
  • References
  • 5 Safety science in the 21st century-a scientific revolution in its making
  • 5.1 Introduction: Thomas S. Kuhn's view on scientific revolutions
  • 5.2 Anomaly and the emergence of scientific discoveries
  • 5.3 Crisis and the emergence of scientific theories
  • 5.4 Response to crisis
  • 5.5 Nature and necessity of scientific revolutions and revolutions as changes of world view
  • 5.6 Summary and conclusions
  • Acknowledgment
  • References
  • 6 Chemobrain
  • 6.1 Introduction.
  • 6.2 Cognitive, structural, and functional disruption caused by chemotherapy
  • 6.3 Mechanisms associated with chemobrain
  • 6.3.1 Oxidative stress
  • 6.3.2 Inflammation
  • 6.3.3 Death cellular mechanisms and cellular sensitivity mechanisms
  • 6.3.4 Neurotransmition and other mechanisms
  • 6.3.5 Genetic polymorphisms
  • 6.4 Conclusions and future perspectives
  • Acknowledgments
  • References
  • 2 Methods and toxicity models in toxicology
  • 7 "Predictive in silico toxicology." An update on modern approaches and a critical analysis of its strong and weak points
  • 7.1 Introduction
  • 7.2 Key concepts
  • 7.3 Qualitative toxicology predictions
  • 7.4 Quantitative toxicology predictions
  • 7.5 Structural alerts and rule-based models
  • 7.6 Read-across approaches
  • 7.7 Quantitative structure-activity relationships models
  • 7.8 Molecular docking
  • 7.9 Conclusions
  • References
  • 8 Analytical strategies to study the gut microbiome in toxicology
  • 8.1 Introduction
  • 8.2 Three generations of deoxyribonucleic acid sequencing technologies
  • 8.3 Sequencing of polymerase chain reaction-amplified marker genes
  • 8.4 Whole-metagenome sequencing
  • 8.5 Bioinformatics: from raw reads to biological insights
  • 8.6 Multiomics approaches to get closer to the phenotype
  • 8.7 Can glyphosate inhibit aromatic amino acid synthesis in gut microorganisms as it does in plants?
  • 8.8 Standardizing gut microbiome evaluation in guidelines for the testing of chemical toxicity
  • 8.9 Concluding remarks
  • References
  • 9 Behavioral endpoints in adult and developmental neurotoxicity: the case of organophosphate pesticides
  • 9.1 Developmental exposure to chemicals and brain function
  • 9.1.1 Regulations
  • 9.2 Toxics and the developing brain
  • 9.2.1 Individual differences: sex and genetic vulnerability
  • 9.2.2 Epigenetics and fetal programming.
  • 9.3 Neurodevelopmental exposures and behavioral assessment
  • 9.4 Organophosphate pesticides and behavior
  • 9.4.1 Humans
  • 9.4.2 Animal models
  • 9.5 Conclusion
  • References
  • 10 Nuclear factor erythroid 2-related factor 2-mediated antioxidant response as an indicator of oxidative stress
  • 10.1 Introduction
  • 10.2 NRF2 activation and oxidative stress
  • 10.2.1 Overview on NRF2
  • 10.2.2 Oxidative stress and oxidative damage
  • 10.2.3 Relationship between oxidative stress and NRF2 activation
  • 10.3 Application of NRF2-ARE reporter systems in drug discovery and risk assessment
  • 10.3.1 NRF2-ARE as a therapeutic target
  • 10.3.2 NRF2-ARE pathway in risk assessment
  • 10.3.3 NRF2-ARE reporter systems
  • 10.4 How should we interpret the data on NRF2 activation and suppression?
  • 10.4.1 Is the antioxidant response a meaningful indicator of oxidative stress?
  • 10.4.2 General recommendations on biomarker selection for oxidative stress characterization
  • 10.5 Conclusions and perspectives
  • Acknowledgments
  • References
  • 11 The potential of complex in vitro models in pharmaceutical toxicology
  • 11.1 Issues with the use of in vitro cell culture systems in pharmaceutical toxicology
  • 11.1.1 The issue of pharmacological attrition: toxicity and efficacy
  • 11.1.2 The need to improve on 2D in vitro models
  • 11.2 Description of microphysiological systems, a complex in vitro model subtype
  • 11.2.1 What are microphysiological systems?
  • 11.2.2 Past to present: the evolution of MPS technology
  • 11.2.3 What are the main applications of MPS?
  • 11.3 Potential for replacement of 2D in vitro and animal models (3Rs)
  • 11.3.1 Implementation of MPS in pharmacological research
  • 11.4 Regulatory aspects of the use of CIVMs
  • 11.4.1 Are MPS ready for implementation and regulatory use?
  • References
  • 3 New insights in risk assessment.
  • 12 Health-based exposure limits and toxicology in the pharmaceutical industry
  • 12.1 Introduction: cross-contamination control and history of health-based exposure limits
  • 12.2 Health-based exposure limits
  • 12.3 PDE derivation methodologies
  • 12.4 Industrial challenges
  • 12.5 Conclusion
  • References
  • 13 The hormetic dose response: implications for risk assessment
  • 13.1 Oxidative stress in the living organisms: the background
  • 13.2 A summary of the main dose-response models
  • 13.3 Hormesis: a historical overview
  • 13.4 Hormesis: occurrence, frequency, and quantitative features
  • 13.5 Hormesis implications in toxicological testing and risk assessment
  • Acknowledgments
  • References
  • 14 Endocrine disruption and human health risk assessment in the light of real-life risk simulation
  • 14.1 Introduction
  • 14.2 EDCs and the RLRS concept
  • 14.2.1 RLRS concept
  • 14.2.2 Mixtures
  • 14.2.3 Long-term exposure
  • 14.2.4 Low doses
  • 14.2.5 Nonmonotonic dose-response
  • 14.2.6 Implications on testing
  • 14.3 Key points of risk assessment of EDs
  • 14.3.1 Threshold or nonthreshold?
  • 14.3.2 Adversity
  • 14.3.3 Mode of action and causality
  • 14.4 Conclusion
  • Acknowledgment
  • References
  • 15 Toxicity data as the basis for acute and short-term emergency exposure guidance
  • 15.1 Introduction: emergency exposures as risk-risk trade-off situations
  • 15.2 General principles of risk assessment
  • 15.2.1 Risk
  • 15.2.2 Dose-response relationships
  • 15.2.3 Exposure durations
  • 15.2.4 Extrapolating the point of departure
  • 15.3 Risk and chemical exposures
  • 15.3.1 Risk and safety are relative terms
  • 15.3.2 Exposures from chemical emergencies
  • 15.3.3 Protecting health during chemical emergencies
  • 15.4 Toxicity data and interpretation
  • 15.4.1 Effect severity
  • 15.4.2 Experimental exposure duration.

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