Advances in Molecular Toxicology

Advances in Molecular Toxicology (eBook)

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2014 | 1. Auflage
278 Seiten
Elsevier Science (Verlag)
978-0-444-63390-3 (ISBN)
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Advances in Molecular Toxicology features the latest advances in all of the subspecialties of the broad area of molecular toxicology. Toxicology is the study of poisons, and this series details the study of the molecular basis by which a vast array of agents encountered in the human environment and produced by the human body itself manifest themselves as toxins. Not strictly limited to documenting these examples, the series is also concerned with the complex web of chemical and biological events that give rise to toxin-induced symptoms and disease. The new technologies that are being harnessed to analyze and understand these events will also be reviewed by leading workers in the field. Advances in Molecular Toxicology will report progress in all aspects of these rapidly evolving molecular aspects of toxicology with a view toward detailed elucidation of progress on the molecular level and on advances in technological approaches employed. - Cutting-edge reviews by leading workers in the discipline - In-depth dissection of molecular aspects of interest to a broad range of scientists, physicians and any student in the allied disciplines - Leading edge applications of technological innovations in chemistry, biochemistry and molecular medicine
Advances in Molecular Toxicology features the latest advances in all of the subspecialties of the broad area of molecular toxicology. Toxicology is the study of poisons, and this series details the study of the molecular basis by which a vast array of agents encountered in the human environment and produced by the human body itself manifest themselves as toxins. Not strictly limited to documenting these examples, the series is also concerned with the complex web of chemical and biological events that give rise to toxin-induced symptoms and disease. The new technologies that are being harnessed to analyze and understand these events will also be reviewed by leading workers in the field. Advances in Molecular Toxicology will report progress in all aspects of these rapidly evolving molecular aspects of toxicology with a view toward detailed elucidation of progress on the molecular level and on advances in technological approaches employed. - Cutting-edge reviews by leading workers in the discipline- In-depth dissection of molecular aspects of interest to a broad range of scientists, physicians and any student in the allied disciplines- Leading edge applications of technological innovations in chemistry, biochemistry and molecular medicine

Front Cover 1
Advances in Molecular Toxicology 4
Copyright 5
Contents 6
Contributors 10
Preface 12
Chapter One: The Mechanistic Complexities of Phycotoxins: Toxicology of Azaspiracids and Yessotoxins 14
1. Introduction 15
2. Azaspiracids 16
2.1. Human effects 17
2.2. Interaction with other coexisting toxins 18
2.3. Apoptosis 18
2.4. Calcium and cAMP 20
2.5. Cytoskeleton and morphology 22
2.6. Membrane channels and receptors 23
3. Yessotoxins 27
3.1. Human effects and toxicology 27
3.2. Apoptosis 29
3.3. Calcium, phosphodiesterases, and cAMP 33
3.4. Mitochondria 35
3.5. Cytosolic proteins, gene expression, and memory 37
Acknowledgments 39
References 39
Chapter Two: Advances in the Analysis of Challenging Food Contaminants: Nanoparticles, Bisphenols, Mycotoxins, and Bromin... 48
1. Introduction 49
2. Analytical Methodology for the Analysis of Nanoparticles 51
2.1. Separation and characterization of nanoparticles 53
2.1.1. Centrifugation 53
2.1.2. Chromatography and related techniques 54
2.2. Imaging and characterization of nanoparticles 55
2.3. Biocompatibility studies 58
3. Analytical Methodology for the Analysis of Bisphenols 63
3.1. Sample treatment 65
3.2. LC and GC-MS analysis of bisphenols and derivatives thereof 67
4. Analytical Methodology for the Analysis of Mycotoxins 70
4.1. Aflatoxins 72
4.2. Ochratoxins 72
4.3. Patulin 74
4.4. Ergot alkaloid 74
4.5. Fumonisins 74
4.6. Zeralenone 75
4.7. Trichothecenes 75
4.8. Strategies in the analysis of mycotoxins 75
5. Analytical Methodology for the Analysis of BFRs 77
5.1. Extraction of liquid samples 83
5.2. Extraction of solid samples 86
5.3. Clean-up 87
5.4. Analysis of BFRs 89
6. Conclusions 94
Acknowledgments 97
References 97
Chapter Three: Mycotoxins from Alternaria: Toxicological Implications 120
1. Introduction 121
2. Chemical Structures 122
3. Acute Toxicity 123
4. Toxicokinetics and Metabolism 124
5. Genotoxicity and Related Mechanism 128
6. Estrogenic Activity and Related Mechanisms 128
7. Mutagenicity and Carcinogenicity 129
8. Gastrointestinal Stability of AOH and ALT Under In Vitro Human Conditions 130
9. Conclusions and Outlook 132
References 132
Chapter Four: Food-Borne Topoisomerase Inhibitors: Risk or Benefit 136
1. Introduction 137
2. Catalytic Enzyme Cycle 138
2.1. Topoisomerase I 139
2.2. Topoisomerase II 140
3. Drug-DNA Interaction: ``Inhibitor Versus Poison´´ 144
4. Topoisomerase Inhibitors in Cancer Therapy 145
4.1. Topoisomerase I 146
4.2. Topoisomerase II 147
5. Secondary Plant Constituents as Topoisomerase Inhibitors 148
5.1. Isoflavones 148
5.2. Catechins 152
5.3. Flavones and flavonols 156
5.4. Anthocyanins 160
5.5. Other polyphenols: Curcumin and resveratrol 163
5.6. Interference of food ingredients with classical topoisomerase poisons 168
6. Conclusion 173
Acknowledgments 174
References 174
Chapter Five: Toxicity of Plasmonic Nanomaterials and Their Hybrid Nanocomposites 186
1. Introduction 187
2. Toxicity Testing and Risk Assessment of Nanomaterials 189
3. Toxicity Evaluation 191
4. Animal Testing for Toxicity 191
5. Factors Affecting Nanotoxicology 192
5.1. Effect of size, concentration, and surface area 192
5.2. Effect of animal model 193
5.3. Purity 194
5.4. Surface charge and chemistry 194
6. Genotoxicology 195
7. The Most Common Genotoxicological Tests 197
7.1. 8-Hydroxydeoxyguanosine DNA adducts 197
7.2. Micronucleus test 198
8. Genotoxicity of Plasmonic Nanomaterials 199
8.1. Gold nanoparticles 199
9. Evaluation of Genotoxicity of Magneto-Plasmonic Hybrid Nanocomposites 200
9.1. Genotoxicity of the Au-Co NPs 200
9.1.1. Gene expression 201
9.1.2. Micronucleus assay 203
9.1.3. Determination of glutathione peroxidase activity 204
9.1.4. Generation of 8-hydroxy-2-deoxyguanosine 205
10. Conclusion 209
References 210
Chapter Six: Aluminum Phytotoxicity: Physiological Approaches and Tolerance 216
1. General Considerations 217
2. Aluminum and Plants Responses 217
2.1. Plant growth 217
2.2. Nutrient imbalances 220
3. Aluminum and the Apoplast-Symplast Continuum 225
4. Aluminum and Oxidative Stress 227
5. Aluminum and Callose Deposition 230
6. Aluminum and Photosynthesis 231
7. Aluminum Tolerance 232
7.1. Mechanisms involving Al exclusion 233
7.2. Mechanisms involved in internal Al detoxification 237
8. Final Remarks 238
Acknowledgments 239
References 239
Index 250

Chapter Two

Advances in the Analysis of Challenging Food Contaminants


Nanoparticles, Bisphenols, Mycotoxins, and Brominated Flame Retardants


Lubinda Mbundi*; Hector Gallar-Ayala; Mohammad Rizwan Khan; Jonathan L. Barber§; Sara Losada§; Rosa Busquets,1    * Blond McIndoe Research Foundation, Queen Victoria Hospital, East Grinstead, West Sussex, United Kingdom
† LUNAM, Ecole Nationale Vétérinaire, Agroalimentaire et de l’Alimentation Nantes Atlantique (Oniris), Laboratoire d’Etude des résidus et Contaminants dans les Aliments (LABERCA), Nantes, France
‡ Advanced Materials Research Chair, Department of Chemistry, College of Science, King Saud University, Riyadh, Kingdom of Saudi Arabia
§ Centre for Environment, Fisheries and Aquaculture Sciences (Cefas), Lowestoft, Suffolk, United Kingdom
¶ School of Chemistry and Pharmacy, Kingston University, Faculty of Science, Engineering and Computing, Kingston Upon Thames, United Kingdom
1 Corresponding author: email address: r.busquets@kingston.ac.uk

Abstract


Nanoparticles, bisphenols, mycotoxins, and brominated flame retardants are highly relevant species toxicologically that can contaminate food and drink through intentional administration or unintentionally from their migration from diverse sources such as packaging materials, cooking utensils, environmental contamination, and fungal activity. Although seemingly different, these contaminants share the common feature of being difficult to isolate and analyze in food. This chapter highlights the different challenges associated with the determination of the study toxins in food and drink and discusses current methods of analysis as well as methods and strategies to overcome the analytical challenges.

Keywords

Nanoparticles

Nanomaterials

Bisphenols

Mycotoxins

Brominated flame retardants

Food contaminants

1 Introduction


Nutrients and food toxicants are two sides of the same coin. Since we ingest hundreds of kilograms of food and drink yearly, we are potentially exposed to a wide range of toxicants, some of which are inherent to food and some from external sources. Naturally inherent toxins include for instance reaction products of precursors naturally present in the food matrix during the cooking processes [1,2]. Toxins introduced to food and drink intentionally include different agents used to improve the food quality or serve as preservative or reaction products thereof [3,4]. However, toxins can also enter food unintentionally through migration from external sources such as cooking utensils and food packaging [5] and agricultural activities, i.e., the use of pesticides [6] and veterinary drugs [7]. Toxins from the environment are either natural in origin, i.e., food toxins from fungi [8] or of anthropogenic origin such as contaminants that are not efficiently removed in wastewater treatment or that are directly emitted to the environment such as dioxins or flame retardants (FRs) [911].

The intake of such an array of pernicious substances occurs at different doses and rates. Indeed, exposure to food toxins can be a one-off event, intermittent, or in some even chronic when the contaminants are part of food items consumed daily, especially in nonvaried diets. Moreover, as well as being able to pose serious health risks individually, ingested toxins may also act and interact synergistically, leading to increased complexity and severity in the nature of the health threats.

Although efforts toward improved food safety have gone a long way, partly due to improved and varied toxicological and analytical studies, food-related toxins are still being discovered and their accurate determination and identification of their origin are still challenges. In this regard, analytical methods in the accurate identification of chemical sources of food contamination have developed across different disciplines in efforts to improve food safety. Owing to the variety and complexity of food matrices and the presence of species that could potentially interfere with the detection and quantification of target compounds, overcoming selectivity problems remains one of the top priorities of the analytical methodologies [6,12]. To achieve these goals, accurate identification and appropriate extraction or recovery and purification of the toxins are necessary. In this regard, overcoming the effects of the different components of the food matrices such as fat on the accurate detection of the target analyte is essential [13]. However, the challenges associated with producing robust evidence for the identification of contaminants in food [14] are not only affected by the matrix but also affected by the analyte concentration with most target contaminants existing at concentration levels as low as parts per billion to parts per trillion [911,1517]. It is therefore essential that methodologies and instruments used provide highly sensitive and selective determinations. In addition, evidence of the mechanism of toxicity of the identified contaminants is necessary to find technological solutions toward improved food safety. Consequently, the process of identifying, isolating, characterizing, and quantifying toxins in food and drink has become an interdisciplinary effort.

This chapter discusses the latest developments in the analysis of nanoparticles, bisphenols (i.e., bisphenol A, F, E) and bisphenol A-diglycidyl ether (BADGE), brominated FRs (BFRs) such as polybrominated biphenlyls (PBBs), hexabromocyclododecanes (HBCDs), tetrabromobisphenol A (TBBPA), and mycotoxins (i.e., aflatoxin, ochratoxin, fumonisin, zearalenone, and trichothecenes). These are key food contaminants with very different physicochemical characteristics and origin. However, these species share the fact that they are difficult to analyze in food. The chapter discusses strategies used to determine each of the contaminants in individual sections, highlighting key approaches to analytical problems and the solutions developed to address them. These include the need to break away from traditional techniques used for molecular identification or awareness of alterations to the target contaminants in the analysis of nanoparticles, the special relevance of analysis of blanks and selectivity in the determination of bisphenols, and the difficulties of working with families of numerous contaminants and food matrices that are likely to be contaminated such as the case of FRs and mycotoxins.

2 Analytical Methodology for the Analysis of Nanoparticles


In recent years, the development and advancement of nanotechnology have increased and the use of nanomaterials is making a significant impact in varied fields such as electronics, water treatment and environmental remediation, engineering, medicine, and food technology. However, little is known about the potential toxicity of these nanomaterials to the environment and health. This problem is in part exacerbated by the lack of a clear definition of nanotechnology and nanomaterials. Due to the multidisciplinary nature of this field, there exist an array of nanotechnology and nanomaterials’ definitions as each scientific discipline adjusts to the new findings of what is a dynamic research effort. Moreover, the same dynamism leads to ambiguity in meanings, and to uncertainty in the overall impact, this field has in the commercialization of nanomaterial-containing products [18].

Recently, the United Kingdom House of Lords Science and Technology Committee recommended that the term nanoscale should encompass all materials with dimension below 1000 nm for regulatory purpose [19]. However, other organizations such as the International Standards Organization (ISO) and American Society for Testing and Materials (ASTM) refer to nanotechnology as the process of understanding and controlling of matter at dimensions between approximately 1 and 100 nm, where unique phenomena enable novel applications [20,21]. As such, nanomaterials are generally referred to as particles that have at least one dimension measuring 1–100 nm and chemically behave differently from bulk materials thereof [18,22]. As such, while governments and regulatory organizations responding to public sentiment are migrating toward sizes larger than 100 nm for nanoscale, the materials sciences community has tended to stick to the 100 nm upper limit and in some fields (i.e., particle physics), sizes as low as 30 nm are used since it is at these sizes where unique, novel, and unexpected nanoscale properties are observed [18].

The use of nanomaterials is on the increase and it is estimated that 58,000 tons of nanomaterials will be used per year in the years 2011–2020 [23] and the amount and variety of nanomaterials that find their way into food and drink are unsurprisingly on the increase too. This is of great concern and has led to growth in the efforts directed at understanding the toxicity of the materials in food and drink as evident from the number of publications on the subject. A recent cursory review of the scientific literature from the year 2003 to 2009 in the PubMed database showed an exponential...

Erscheint lt. Verlag 3.10.2014
Mitarbeit Herausgeber (Serie): James C. Fishbein, Jacqueline M. Heilman
Sprache englisch
Themenwelt Medizin / Pharmazie Allgemeines / Lexika
Medizin / Pharmazie Gesundheitsfachberufe
Medizin / Pharmazie Medizinische Fachgebiete Pharmakologie / Pharmakotherapie
Studium 2. Studienabschnitt (Klinik) Pharmakologie / Toxikologie
ISBN-10 0-444-63390-1 / 0444633901
ISBN-13 978-0-444-63390-3 / 9780444633903
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