Toxicological Risk Assessment and Multi-System Health Impacts from Exposure

1st Edition - August 1, 2021
Editor: Aristidis M. Tsatsakis
Language: English
Paperback ISBN:
9 7 8 - 0 - 3 2 3 - 8 5 2 1 5 - 9
eBook ISBN:
9 7 8 - 0 - 3 2 3 - 8 5 3 5 8 - 3

Toxicological Risk Assessment and Multisystem Health Impacts From Exposure highlights the emerging problems of human and environmental health attributable to cumulative and multip… Read more

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Toxicological Risk Assessment and Multisystem Health Impacts From Exposure highlights the emerging problems of human and environmental health attributable to cumulative and multiple sources of long-term exposure to environmental toxicants. The book describes the cellular, biological, immunological, endocrinologic, genetic, and epigenetic effects of long-term exposure. It examines how the combined exposure to nanomaterials, metals, pharmaceuticals, multifrequency radiation, dietary mycotoxins, and pesticides accelerates ecotoxicity in humans, animals, plants, and the larger environment. The book goes on to also offer insights into mixture risk assessments, protocols for evaluating the risks, and how this information can serve the regulatory agencies in setting safer exposure limits. The book is a go-to resource for scientists and professionals in the field tackling the current and emerging trends in modern toxicology and risk assessment.

Cover image
Title page
Table of Contents
Copyright
List of contributors
About the editor
Preface
Endorsements
Part 1: Modern tools and concepts in toxicology testing
Chapter 1. Mixture toxicity evaluation in modern toxicology
Abstract
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
Chapter 2. Alternative methods to animal experimentation and their role in modern toxicology
Abstract
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
2.5 Strengthening international harmonization and cooperation on the validation and implementation of alternative methods
2.6 Conclusion
References
Chapter 3. The exposome—a new paradigm for non-animal toxicology and integrated risk assessment
Abstract
3.1 Introduction
3.2 Advancing the toxicological paradigm through exposome
3.3 Key advances proposed by the exposome paradigm in toxicology
References
Chapter 4. In silico toxicology, a robust approach for decision-making in the context of next-generation risk assessment
Abstract
4.1 Introduction
4.2 Relevance and applicability domain of in silico methods
4.3 In silico computational methods for predictive toxicology of chemicals
4.4 Application of in silico methods in regulatory science
4.5 Conclusions and future directions
References
Chapter 5. Safety science in the 21st century—a scientific revolution in its making
Abstract
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
Chapter 6. Chemobrain
Abstract
6.1 Introduction
6.2 Cognitive, structural, and functional disruption caused by chemotherapy
6.3 Mechanisms associated with chemobrain
6.4 Conclusions and future perspectives
Acknowledgments
References
Part 2: Methods and toxicity models in toxicology
Chapter 7. “Predictive in silico toxicology.” An update on modern approaches and a critical analysis of its strong and weak points
Abstract
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
Chapter 8. Analytical strategies to study the gut microbiome in toxicology
Abstract
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
Chapter 9. Behavioral endpoints in adult and developmental neurotoxicity: the case of organophosphate pesticides
Abstract
9.1 Developmental exposure to chemicals and brain function
9.2 Toxics and the developing brain
9.3 Neurodevelopmental exposures and behavioral assessment
9.4 Organophosphate pesticides and behavior
9.5 Conclusion
References
Chapter 10. Nuclear factor erythroid 2-related factor 2-mediated antioxidant response as an indicator of oxidative stress
Abstract
10.1 Introduction
10.2 NRF2 activation and oxidative stress
10.3 Application of NRF2-ARE reporter systems in drug discovery and risk assessment
10.4 How should we interpret the data on NRF2 activation and suppression?
10.5 Conclusions and perspectives
Acknowledgments
References
Chapter 11. The potential of complex in vitro models in pharmaceutical toxicology
Abstract
11.1 Issues with the use of in vitro cell culture systems in pharmaceutical toxicology
11.2 Description of microphysiological systems, a complex in vitro model subtype
11.3 Potential for replacement of 2D in vitro and animal models (3Rs)
11.4 Regulatory aspects of the use of CIVMs
References
Part 3: New insights in risk assessment
Chapter 12. Health-based exposure limits and toxicology in the pharmaceutical industry
Abstract
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
Chapter 13. The hormetic dose response: implications for risk assessment
Abstract
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
Chapter 14. Endocrine disruption and human health risk assessment in the light of real-life risk simulation
Abstract
14.1 Introduction
14.2 EDCs and the RLRS concept
14.3 Key points of risk assessment of EDs
14.4 Conclusion
Acknowledgment
References
Chapter 15. Toxicity data as the basis for acute and short-term emergency exposure guidance
Abstract
15.1 Introduction: emergency exposures as risk–risk trade-off situations
15.2 General principles of risk assessment
15.3 Risk and chemical exposures
15.4 Toxicity data and interpretation
15.5 Some examples of acute and short-term exposure guidance values
15.6 Decision-making
15.7 Conclusions
References
Further reading
Chapter 16. Renal mitochondria as sentinels for exposures to environmental toxicants and nephrotoxic drugs
Abstract
16.1 Introduction: the kidneys as a sensitive target for diverse chemicals and drugs
16.2 Biomarkers of kidney function
16.3 Mitochondria as early target sites in diverse diseases and pathological states
16.4 Renal mitochondria as early and sensitive targets for environmental toxicants and nephrotoxic drugs
16.5 Trichloroethylene-induced proximal tubular injury
16.6 Summary and conclusions
Acknowledgments
References
Part 4: Clinical biomarkers updates
Chapter 17. Updates on current biomarkers in toxicology
Abstract
17.1 Introduction
17.2 Toxicity testing models and biomarkers
17.3 Systems toxicity biomarkers
17.4 Conclusion and future perspectives
Acknowledgment
References
Chapter 18. The role of extracellular matrix in allergic contact dermatitis pathogenesis
Abstract
18.1 Introduction
18.2 ACD—a sterile inflammation
18.3 Mechanisms involved in the pathogenesis of ACD
18.4 Extracellular matrix
18.5 The role of HA in the onset and propagation of ACD
18.6 ECM proteins in the process of skin sensitization
18.7 The contribution of MMPs and their endogenous TIMPs
18.8 Conclusion and summary
References
Chapter 19. Review of current neurotoxicology biomarkers
Abstract
19.1 Introduction
19.2 Biomarkers of exposure
19.3 Biomarkers of effect
19.4 Biomarkers of susceptibility
19.5 Metals
19.6 Pesticides
19.7 Organic solvents
19.8 Challenges and future perspectives
Acknowledgments
References
Chapter 20. Modern aspects of immunotoxicology
Abstract
20.1 Introduction
20.2 Immune system
20.3 Immunotoxicity
20.4 Assessment of immunotoxicity
20.5 Examples
Bibliography
Chapter 21. Toxicology of neurodegenerative diseases
Abstract
21.1 Introduction
21.2 Alzheimer’s disease
21.3 Parkinson’s disease
21.4 Amyotrophic lateral sclerosis
21.5 Summary and conclusions
Acknowledgments
References
Chapter 22. Toxicogenetics—Pharmacogenetics: Genetic variability profiling for xenobiotic response heterogeneity
Abstract
22.1 Introduction
22.2 Human genetic variation
22.3 Single nucleotide polymorphisms
22.4 The role of genetic polymorphisms in pharmacokinetics and pharmacodynamics of xenobiotics
22.5 SNP profiling in clinical trials
22.6 Pharmacogenetic testing: ethical and moral concerns
22.7 Summary and conclusions
References
Chapter 23. Current and emerging concepts of cardiotoxicity
Abstract
23.1 Cardiotoxicity of chemotherapeutics in humans
23.2 Known cardiotoxic manifestations of industrial chemicals in humans
23.3 Alleged cardiotoxicity in humans from long-term use of chemical products (anabolic steroids, pesticides)
23.4 Animal models and their application for identifying cardiotoxicity
References
Chapter 24. Metabolomics: diagnostic and therapeutic applications in clinical medicine and pharmacology
Abstract
24.1 Metabolomics: from genes to phenotype
24.2 Basic principles and strategies of metabolomics
24.3 Diagnostic applications of metabolomics
24.4 Treatment selection and personalization with metabolomics
References
Chapter 25. Metabolomics methodology and workflow: challenges and future prospects
Abstract
25.1 Metabolomics techniques and their applications
25.2 Comparison of untargeted and targeted metabolomic analysis
25.3 Challenges of metabolic biomarker identification and validation
25.4 Metabolomics in the clinic: where are we?
References
Chapter 26. Telomere length: associations with nutrients and xenobiotics
Abstract
26.1 Introduction
26.2 Associations of nutrients with TL
26.3 Telomerase regulators
26.4 Endocrine disrupting chemicals and TL
26.5 Conclusions
References
Part 5: Epidemiology and public health toxicology issues
Chapter 27. Dismissing the use of P-values and statistical significance testing in scientific research: new methodological perspectives in toxicology and risk assessment
Abstract
27.1 Introduction
27.2 Statistical tools to interpret causation in epidemiology, toxicology, and health sciences
27.3 Conclusions
References
Chapter 28. Modern approaches for the assessment of human exposure to dietary mycotoxins
Abstract
28.1 Introduction
28.2 Risk assessment of dietary mycotoxins
28.3 Hazard identification
28.4 Hazard characterization
28.5 Exposure assessment
28.6 Risk characterization
28.7 Exposure assessment to mycotoxins using food and consumption data
28.8 Exposure assessment to mycotoxins using biomarkers
28.9 Concluding remarks and future perspectives
Acknowledgments
References
Chapter 29. Tobacco toxicity and regulatory science
Abstract
29.1 The evolving tobacco product as a driving need for regulatory toxicology
29.2 Tobacco constituents as a driver of risk assessment
29.3 Flavorings and their regulatory implications
29.4 Toxicity of tobacco products and real-life risk simulations in tobacco products
29.5 Regulatory framework of tobacco products in Europe and globally
29.6 Conclusions
References
Chapter 30. Dethroning the crown. From the kinetics and dynamics of COVID–19 diagnosis to promising treatments
Abstract
30.1 Introduction
30.2 Epidemiology
30.3 Transmission
30.4 Diagnosing SARS–CoV–2 infection
30.5 Treating SARS–CoV–2 infection
30.6 Conclusion
References
Chapter 31. Toxicology issues related to the COVID–19 outbreak
Abstract
31.1 Introduction
31.2 Centrality of immune system dysfunction in pandemics
31.3 Immune system toxicology
31.4 Treatments for COVID–19
31.5 Strategic/proactive
31.6 Conclusions
References
Chapter 32. Risk assessment for heat stress during work and leisure
Abstract
32.1 Introduction
32.2 Factors affecting the risk for heat strain
32.3 Concluding remarks
References
Part 6: Pharmaceuticals and nutraceuticals toxicology updates
Chapter 33. Polyphenols: the hallmark of endothelial dysfunction combatants
Abstract
33.1 Background
33.2 Dietary polyphenol intake and major food sources
33.3 Endothelial dysfunction—general pathological impairments
33.4 Polyphenols as modulating agents of vascular and endothelial function—preventive or repairing role
33.5 Effects of natural compounds in metabolic diseases
33.6 Sympathetic regulation by polyphenols
33.7 Conclusions
References
Chapter 34. Effect of diet, pharmaceuticals, and environmental toxicants on gut microbiota imbalance and increased intestinal membrane permeability
Abstract
34.1 Normal gut microbiota
34.2 Dysbiosis
34.3 Causes of dysbiosis
34.4 Result of dysbiosis
34.5 Intestinal barrier and its function
34.6 Maintenance of intestinal membrane integrity
34.7 Intestinal permeability testing
34.8 Components generated in dysbiosis that lead to membrane impermeability
34.9 Result of increased membrane permeability
References
Chapter 35. Hydrogen sulfide: a shifting paradigm
Abstract
35.1 Background
35.2 Physiological functions
35.3 Pathological implications
35.4 Concluding remarks and outlook
References
Chapter 36. Redox biomarkers in toxicology and nutrition: the social link
Abstract
36.1 Introduction
36.2 The biomarker issue in a wide range of scientific disciplines
36.3 The role of redox biomarkers in the interpretation of perturbations in redox equilibrium
36.4 Redox biomarkers in toxicology and nutrition
36.5 Nutrition, toxicology, and redox biology: an interplay
36.6 Concluding remarks
References
Chapter 37. Safety profile of plants and phytoconstituents used in traditional medicine worldwide
Abstract
37.1 Introduction
37.2 Toxic effects due to exposure to medicinal plant extracts
37.3 Toxic effects due to exposure to bioactive compounds of medicinal plants
37.4 Conclusion
References
Part 7: Toxicology of biomaterials and nanomaterials
Chapter 38. Epigenetic mechanisms in nanomaterial toxicity
Abstract
38.1 Epigenetics—introduction
38.2 Nanomaterial application and nanomaterial toxicity
38.3 Epigenetic mechanisms underlying nanomaterial toxicity
38.4 Future applications
References
Chapter 39. Predictive nanotoxicology: from nanotoxicity to nanosafety of select and commonly used nanomaterials
Abstract
39.1 Introduction
39.2 Importance of toxicology of nanoparticles
39.3 Biotoxicity of nanoparticles
39.4 What is “predictive nanotoxicology” and what is its relevance to nanosafety?
39.5 Components for predicting nanotoxicity of silver, cadmium, copper, and titanium nanoparticles
39.6 Scope of predictive nanotoxicology
39.7 Conclusion
References
Chapter 40. The toxicological effects of titanium dioxide nanoparticles on marine microalgae
Abstract
40.1 Introduction
40.2 Titanium dioxide and their polymorphs
40.3 Photocatalytic property
40.4 Applications and release of TiO2 NPs
40.5 Fate and behavior of TiO2 NPs in seawater
40.6 Toxic effects of TiO2 NPs on marine microalgae
40.7 Mechanism of toxicity
40.8 Conclusion
References
Chapter 41. Aquatic nanotoxicology: reference species and omics technologies
Abstract
41.1 Introduction
41.2 Reference species in aquatic nanotoxicology
41.3 Omics in aquatic nanotoxicology
41.4 Conclusion
References
Part 8: Special topics in toxicology
Chapter 42. Toxicity of arsenicals in diseases: friend or foe?
Abstract
42.1 Introduction
42.2 Arsenicals in diseases: chronic arsenic exposure through drinking water
42.3 Arsenicals in medicine: molecular mechanism through which iAs exerts anticancer effect
42.4 Conclusion
References
Chapter 43. Toxicity of psychedelic drugs
Abstract
43.1 Introduction
43.2 A short history of psychedelic substances
43.3 Classification of serotoninergic hallucinogens based on their chemical structures
43.4 Currently used serotoninergic hallucinogens
43.5 Toxicokinetics of serotoninergic hallucinogens
43.6 Toxicodynamics of serotoninergic hallucinogens
43.7 Diagnosis of intoxication
43.8 Conclusions
References
Chapter 44. Immunotoxicity of pesticides: current knowledge and perspectives
Abstract
44.1 Introduction
44.2 Pesticides
44.3 Carbamates
44.4 Organophosphates
44.5 Organochlorines
44.6 Pyrethroids
44.7 Neonicotinoid compounds
44.8 Phenoxy compounds
44.9 Risk assessment
44.10 Conclusion
References
Chapter 45. Glyphosate-based herbicides: evidence of immune-endocrine-microbiome alteration
Abstract
45.1 Introduction
45.2 Evidence of glyphosate-induced immune alterations
45.3 Evidence of glyphosate-induced endocrine alterations
45.4 Possible role of the microbiota in glyphosate-induced immune-endocrine alterations
45.5 Conclusion
References
Chapter 46. Ciguatera toxins: toxicity and food safety
Abstract
46.1 Introduction
46.2 Chemical structures and properties of ciguatoxins
46.3 Occurrence and accumulation in seafood
46.4 Toxicity of ciguatera fish-poisoning toxins
46.5 Factors influencing clinical symptoms
46.6 Diagnosis
46.7 Treatment
46.8 Prevention of ciguatera food-poisoning intoxication
46.9 Food safety and regulatory limits
46.10 Conclusion
Acknowledgments
References
Chapter 47. Cannabinoids and psychosis: current challenges of mechanistic toxicology
Abstract
47.1 The pathophysiology of psychotic disorders
47.2 Cannabinoids and psychosis
47.3 Future challenges
Acknowledgments
References
Chapter 48. Electronic cigarettes as a harm reduction concept for public health
Abstract
48.1 Introduction
48.2 Tobacco harm reduction
48.3 Electronic cigarettes
48.4 Risk profile of electronic cigarettes
48.5 Electronic cigarettes and smoking cessation
48.6 Electronic cigarette use by never smokers and youth
48.7 Regulatory perspective on electronic cigarettes
References
Index

Life Sciences

Physical Sciences & Engineering

Social Sciences & Humanities

Health

Toxicological Risk Assessment and Multi-System Health Impacts from Exposure

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Aristidis M. Tsatsakis