| Description |
1 online resource |
| Contents |
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 |
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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 |
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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 |
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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 |
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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 |
| Notes |
Print version record |
| Subject |
Environmental toxicology.
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Hazardous substances -- Risk assessment.
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Ecotoxicology
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Environmental toxicology
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Hazardous substances -- Risk assessment
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| Form |
Electronic book
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| Author |
Tsatsakis, Aristidis M., 1957- editor.
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| ISBN |
9780323853583 |
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0323853587 |
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