| Contributors |
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xix | |
| Foreword |
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xxiii | |
| I Toxicity Testing Models And Biomarkers |
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5 | (2) |
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2 Rodent Models for Toxicity Testing and Biomarkers |
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7 | (1) |
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8 | (3) |
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11 | (2) |
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Routes of Test Article Administration |
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13 | (10) |
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23 | (1) |
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End Point Measurement Techniques |
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23 | (9) |
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32 | (4) |
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36 | (9) |
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Routes of Test Substance Administration |
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45 | (8) |
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End Point Data Collection |
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53 | (2) |
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55 | (1) |
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55 | (3) |
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58 | (1) |
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58 | (1) |
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58 | (1) |
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Blood Collection Techniques |
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59 | (1) |
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59 | (1) |
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59 | (1) |
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60 | (1) |
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60 | (1) |
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61 | (1) |
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61 | (1) |
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62 | (1) |
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63 | (1) |
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63 | (1) |
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63 | (1) |
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63 | (1) |
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64 | (1) |
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Strain-Related Considerations |
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64 | (1) |
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65 | (2) |
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Chinese Hamster Ovary Cell Chromosome Aberrations |
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67 | (1) |
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Syrian Hamster Embryo Cell Transformation Assay |
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67 | (1) |
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67 | (2) |
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Concluding Remarks and Future Directions |
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69 | (1) |
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69 | (6) |
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3 Gottingen Minipigs as Large Animal Model in Toxicology |
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Pigs and Minipigs in Translational Research |
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75 | (1) |
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Legislation and Species Selection |
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75 | (1) |
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Gottingen Minipigs as an Animal Model |
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76 | (1) |
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Dosing Routes and Formulations |
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77 | (1) |
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78 | (1) |
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78 | (1) |
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78 | (3) |
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Organ Weight, Background Findings, and Comparative Aspects |
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81 | (2) |
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83 | (2) |
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85 | (1) |
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Concluding Remarks and Future Directions |
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86 | (1) |
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86 | (5) |
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4 Nonhuman Primates in Preclinical Research |
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91 | (1) |
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Clinical Pathology in NHPs |
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91 | (7) |
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Background Microscopic Lesions in NHPs |
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98 | (2) |
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Concluding Remarks and Future Directions |
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100 | (1) |
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100 | (3) |
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5 Biomarkers of Toxicity in Zebrafish |
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103 | (1) |
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103 | (1) |
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Ecotoxicological Biomarkers of Toxicity |
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103 | (1) |
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Examples of Biomarkers of Fish Toxicity |
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104 | (4) |
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An Example of an Established Biomarker: Vitellogenin |
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108 | (2) |
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110 | (1) |
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Concluding Remarks and Future Directions |
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111 | (1) |
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111 | (1) |
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111 | (4) |
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6 Mechanistic Toxicology Biomarkers in Caenorhabditis elegans |
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115 | (1) |
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C. elegans and Biomarkers |
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115 | (2) |
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117 | (2) |
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Neurodegenerative Diseases and Gene-Environment Interactions |
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119 | (3) |
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Concerns Unique to C. elegans |
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122 | (3) |
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Concluding Remarks and Future Directions |
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125 | (1) |
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125 | (1) |
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125 | (4) |
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7 Potential of Small Animals in Toxicity Testing: Hope From Small World |
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129 | (2) |
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Toxicity Testing Using Small Animals |
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131 | (6) |
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Concluding Remarks and Future Directions |
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137 | (1) |
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137 | (1) |
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137 | (6) |
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8 Alternative Animal Toxicity Testing and Biomarkers |
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143 | (1) |
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Use of Alternatives to Animal Testing and Biomarkers |
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144 | (1) |
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Reasons for Developing Alternatives to Animal Tests and Biomarkers |
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144 | (1) |
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Examples of Organizations' Researching and Funding Alternatives to Animal Testing and Biomarker Development |
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145 | (2) |
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Achieving 3Rs With Minimal to No Animal Testing by Using Biomarkers |
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147 | (2) |
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Applications of In Vitro Tests and Biomarkers |
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149 | (10) |
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Concluding Remarks and Future Directions |
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159 | (1) |
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159 | (4) |
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9 Adverse Outcome Pathways and Their Role in Revealing Biomarkers |
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163 | (1) |
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Adverse Outcome Pathways: Principles of Development and Assessment |
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164 | (2) |
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Adverse Outcome Pathway Framework: Similarities and Differences With Biomarkers |
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166 | (1) |
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Adverse Outcome Pathways as a Tool to Retrieve Biomarkers |
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167 | (1) |
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Biomarkers Depicted From the Adverse Outcome Pathway-Knowledge Base |
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167 | (1) |
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Regulatory Use of Adverse Outcome Pathways |
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168 | (1) |
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Concluding Remarks and Future Directions |
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169 | (1) |
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169 | (4) |
| II Systems Toxicity Biomarkers |
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10 Central Nervous System Toxicity Biomarkers |
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173 | (2) |
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Biomarkers in Neurotoxicology |
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175 | (2) |
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Case Study 1: The Organophosphorus Insecticides |
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177 | (4) |
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Case Study 2: Mild Traumatic Brain Injury |
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181 | (1) |
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Concluding Remarks and Future Directions |
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182 | (1) |
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182 | (1) |
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182 | (5) |
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11 Peripheral Nervous System Toxicity Biomarkers |
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Tirupapuliyur V. Damodaran |
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187 | (1) |
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Types of Biomarkers of the Peripheral Nervous System |
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188 | (1) |
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Peripheral Nervous System Biomarker Methodology |
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188 | (1) |
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Neurological and Physical Examination |
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189 | (1) |
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Sample Requirements for Biomarker Testing |
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189 | (3) |
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Biomarkers of Traumatic Brain Injury Affecting Peripheral Nervous System |
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192 | (10) |
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202 | (2) |
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Biomarkers of Enteric Nervous System |
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204 | (1) |
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Emerging Avenues of Peripheral Nervous System Biomarker Developments: Exosomes |
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204 | (1) |
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205 | (1) |
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Concluding Remarks and Future Directions |
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205 | (1) |
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205 | (4) |
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12 Cardiovascular Toxicity Biomarkers |
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209 | (1) |
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Physiology of the Cardiovascular System |
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210 | (1) |
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211 | (1) |
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Mitochondrial Dysfunction |
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211 | (1) |
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212 | (1) |
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212 | (1) |
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Biomarker of Myocardial Ionic Dysfunction |
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212 | (1) |
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213 | (1) |
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Biomarkers of Wall Stretch |
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213 | (1) |
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214 | (1) |
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Biomarkers of Inflammation |
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215 | (1) |
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215 | (1) |
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216 | (1) |
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216 | (1) |
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217 | (1) |
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Markers of Drug-Induced Toxicity |
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217 | (1) |
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Cardiac Biomarkers of Illegal Drugs, Chemicals, and Terror Agents |
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217 | (3) |
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Future Trends in Cardiovascular Biomarkers |
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220 | (3) |
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Risk Prediction of Cardiovascular Events |
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223 | (1) |
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Concluding Remarks and Future Directions |
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224 | (1) |
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224 | (5) |
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13 Respiratory Toxicity Biomarkers |
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229 | (1) |
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230 | (1) |
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Causes of Lung Injury and Disease |
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231 | (1) |
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Types of Lung Injuries and Pathologies |
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231 | (2) |
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Sampling Methods for Analysis of Biomarkers of Lung Toxicity |
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233 | (2) |
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Types of Lung Toxicity Biomarkers |
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235 | (11) |
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Concluding Remarks and Future Directions |
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246 | (1) |
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246 | (1) |
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246 | (1) |
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246 | (5) |
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14 Hepatic Toxicity Biomarkers |
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251 | (1) |
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Overview of Liver Physiology, Toxicity, and Pathology |
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252 | (3) |
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Review of Existing Biomarkers of Liver Toxicity |
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255 | (2) |
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Review of Emerging Biomarkers |
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257 | (6) |
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Biomarker Qualification and Validation |
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263 | (1) |
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Concluding Remarks and Future Directions |
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263 | (1) |
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263 | (4) |
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15 Conventional and Emerging Renal Biomarkers |
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267 | (1) |
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Characteristics of Biomarkers |
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267 | (1) |
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268 | (1) |
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269 | (3) |
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Concluding Remarks and Future Directions |
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272 | (1) |
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273 | (4) |
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16 Gastrointestinal Toxicity Biomarkers |
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277 | (1) |
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NSAID-Induced Gastrointestinal Toxicity |
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277 | (1) |
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Chemotherapy-Induced Gastrointestinal Toxicity |
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277 | (1) |
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Radiation-Induced Gastrointestinal Toxicity |
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278 | (1) |
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Inflammatory Bowel Diseases |
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278 | (1) |
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Biomarkers for Gastrointestinal Damage |
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278 | (1) |
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278 | (2) |
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280 | (2) |
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Concluding Remarks and Future Directions |
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282 | (1) |
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Metabolome-Based Biomarkers |
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282 | (1) |
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283 | (4) |
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17 Reproductive Toxicity Biomarkers |
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287 | (1) |
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Male Reproductive Biomarkers |
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287 | (5) |
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Female Reproductive Biomarkers |
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292 | (5) |
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Concluding Remarks and Future Directions |
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297 | (1) |
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298 | (5) |
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18 Biomarkers of Toxicity in Human Placenta |
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303 | (1) |
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Placental Development and Structure |
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304 | (1) |
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Toxic and Hormonally Active Chemicals in Human Placenta |
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305 | (3) |
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Placental Functions and Molecular Pathways Involved in Toxicity |
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308 | (10) |
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Potential Biomarkers of Exposure and Toxicity in Human Placenta |
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318 | (8) |
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Use of Placenta in Regulatory Toxicology- Considerations by Ecvam and Other Organizations |
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326 | (2) |
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Concluding Remarks and Future Directions |
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328 | (1) |
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329 | (12) |
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19 Early Biomarkers of Acute and Chronic Pancreatitis |
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341 | (1) |
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Anatomical, Physiological, and Metabolic Considerations for Pancreatic Injury |
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341 | (1) |
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341 | (1) |
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342 | (1) |
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Biomolecular Basis of Pancreatitis |
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342 | (1) |
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Biomarkers of Acute and Chronic Pancreatitis |
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342 | (1) |
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Abdominal Imaging Techniques |
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343 | (1) |
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Functional Biomarkers of Endocrine and Exocrine Pancreatitis |
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343 | (1) |
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344 | (1) |
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344 | (1) |
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344 | (1) |
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Carbohydrate-Deficient Transferrin |
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345 | (1) |
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Activation By-Products of Pancreatic Trypsinogen and Carboxypeptidase B |
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345 | (1) |
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Elastase and Phospholipase A2 |
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345 | (1) |
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346 | (1) |
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C-Reactive Protein and Pancreatitis-Associated Protein |
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346 | (1) |
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346 | (1) |
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347 | (1) |
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Inflammatory Cytokines and Chemokines |
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347 | (1) |
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Biomarkers of Endocrine and Autoimmune Pancreatitis |
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347 | (1) |
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Ethanol Metabolites and Conjugates |
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347 | (1) |
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Differentially Altered Proteins, Metabolites, Small Molecules, and microRNA |
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348 | (1) |
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Comparison of Biomarkers Between Acute and Chronic Pancreatitis |
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349 | (1) |
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Biomarkers for Early Detection of Pancreatic Cancer |
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350 | (1) |
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350 | (1) |
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Concluding Remarks and Future Directions |
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350 | (1) |
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350 | (5) |
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20 Skeletal Muscle Toxicity Biomarkers |
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355 | (1) |
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355 | (1) |
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355 | (7) |
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362 | (1) |
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362 | (2) |
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364 | (1) |
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365 | (2) |
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367 | (1) |
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368 | (1) |
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Concluding Remarks and Future Directions |
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369 | (1) |
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369 | (6) |
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21 Ocular Biomarkers in Diseases and Toxicities |
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375 | (1) |
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375 | (4) |
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Systemic Agents and Ocular Toxicity |
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379 | (2) |
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Concluding Remarks and Future Directions |
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381 | (1) |
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381 | (4) |
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22 Biomarkers of Ototoxicity |
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385 | (1) |
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Structure and Function of the Normal Auditory System |
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385 | (2) |
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387 | (1) |
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Classification of Chemicals Causing Ototoxicity |
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388 | (4) |
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Factors Modifying Chemical Ototoxicity |
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392 | (1) |
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Underlying Mechanisms of Ototoxicity |
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393 | (1) |
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Functional and Molecular Biomarkers for the Evaluation of Ototoxicity |
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394 | (3) |
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Concluding Remarks and Future Directions |
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397 | (1) |
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397 | (4) |
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23 Blood and Bone Marrow Toxicity Biomarkers |
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401 | (1) |
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401 | (3) |
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Mechanisms of Hematotoxicity |
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404 | (1) |
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Biomarkers of Hematotoxicity |
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405 | (1) |
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Markers of Hematopoietic/Hematologic Toxicity |
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405 | (3) |
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Markers of Bone Marrow Toxicity |
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408 | (1) |
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Markers of Hemostatic Toxicity |
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409 | (1) |
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Concluding Remarks and Future Directions |
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410 | (1) |
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410 | (3) |
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24 Immunotoxicity Biomarkers |
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413 | (1) |
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413 | (1) |
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Lymphoid Organs and Tissues |
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413 | (1) |
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Cells of the Immune System |
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414 | (2) |
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Soluble Mediators of Immunity |
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416 | (1) |
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Mechanisms of Immunotoxicity |
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417 | (1) |
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417 | (1) |
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Biomarkers of Immune Status |
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418 | (4) |
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Biomarkers of Hypersensitivity |
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422 | (1) |
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Biomarkers of Autoimmunity |
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423 | (1) |
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Concluding Remarks and Future Directions |
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423 | (1) |
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424 | (5) |
| III Chemical Agents, Solvents And Gases Toxicity Biomarkers |
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25 Bisphenol A Biomarkers and Biomonitoring |
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429 | (1) |
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Bisphenol A Biomarker Issues in Biomonitoring |
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430 | (2) |
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Exposure and Selected Outcome Studies |
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432 | (1) |
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Large General Population Biomonitoring Programs |
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432 | (6) |
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Pregnant Women, Mother-Infant/Child Pairs, Infants, Children |
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438 | (12) |
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Food Packaging and Bisphenol A Alternatives |
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450 | (1) |
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Concluding Remarks and Future Directions |
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451 | (1) |
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452 | (3) |
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455 | (1) |
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Organophosphates and Carbamates |
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456 | (4) |
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460 | (2) |
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Pyrethrins and Pyrethroids |
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462 | (3) |
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465 | (1) |
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466 | (1) |
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467 | (1) |
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Ivermectin and Selamectin |
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468 | (1) |
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469 | (1) |
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Concluding Remarks and Future Directions |
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470 | (1) |
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470 | (7) |
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27 Herbicides and Fungicides |
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477 | (1) |
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478 | (1) |
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478 | (1) |
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479 | (1) |
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Biomarkers and Biomonitoring of Exposure |
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479 | (17) |
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Concluding Remarks and Future Directions |
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496 | (1) |
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496 | (5) |
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28 Polychlorinated Biphenyls, Polybrominated Biphenyls, and Brominated Flame Retardants |
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501 | (1) |
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Polychlorinated Biphenyls |
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501 | (2) |
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503 | (2) |
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Brominated Flame Retardants |
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505 | (5) |
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Thyroid Hormone Disruption as a Biomarker of Exposure and Effect |
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510 | (1) |
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Perturbed Calcium Homeostasis and Kinase Signaling as Biomarkers of Effect |
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511 | (2) |
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Induction of Cytochrome P450 Enzymes as a Biomarker of Exposure and Effect |
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513 | (1) |
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Concluding Remarks and Future Directions |
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514 | (1) |
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515 | (1) |
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515 | (4) |
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29 Polycyclic Aromatic Hydrocarbons |
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519 | (1) |
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519 | (3) |
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Other Biomarkers of Exposure |
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522 | (1) |
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522 | (1) |
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Biomarkers of Susceptibility |
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523 | (1) |
|
Concluding Remarks and Future Directions |
|
|
524 | (1) |
|
|
|
524 | (1) |
|
|
|
525 | (4) |
|
|
|
|
|
|
|
|
|
|
529 | (1) |
|
Classification of Biomarkers |
|
|
529 | (1) |
|
Selection of an Ideal Biomarker: Benefits and Drawbacks |
|
|
529 | (1) |
|
Biomonitoring of Exposure to Heavy Metals |
|
|
529 | (1) |
|
|
|
530 | (2) |
|
|
|
532 | (4) |
|
|
|
536 | (2) |
|
|
|
538 | (2) |
|
|
|
540 | (1) |
|
|
|
541 | (3) |
|
|
|
544 | (1) |
|
Current Concerns and Biological Relevance |
|
|
545 | (1) |
|
Concluding Remarks and Future Directions |
|
|
546 | (1) |
|
|
|
546 | (5) |
|
|
|
|
|
|
Introduction and Historical Background |
|
|
551 | (1) |
|
|
|
552 | (1) |
|
|
|
553 | (5) |
|
Concluding Remarks and Future Directions |
|
|
558 | (1) |
|
|
|
559 | (2) |
|
32 Biomarkers of Petroleum Products Toxicity |
|
|
|
|
|
|
|
|
|
561 | (1) |
|
|
|
561 | (2) |
|
|
|
563 | (2) |
|
|
|
565 | (1) |
|
|
|
566 | (1) |
|
Concluding Remarks and Future Directions |
|
|
567 | (1) |
|
|
|
567 | (2) |
|
33 Biomarkers of Chemical Mixture Toxicity |
|
|
|
|
|
|
|
|
|
|
|
569 | (1) |
|
Potential Chemical Mixtures |
|
|
569 | (2) |
|
Biomonitoring for Assessing Human Exposure to Chemical Mixtures |
|
|
571 | (3) |
|
Risk Assessment of Combined Actions of Chemical Mixtures |
|
|
574 | (2) |
|
Biomarkers of Target Organ Toxicity of Chemical Mixtures |
|
|
576 | (5) |
|
Nonspecific Biomarkers of Toxic Response |
|
|
581 | (1) |
|
Concluding Remarks and Future Directions |
|
|
582 | (1) |
|
|
|
583 | (4) |
|
34 Biomarkers of Toxic Solvents and Gases |
|
|
|
|
|
|
|
587 | (1) |
|
|
|
588 | (1) |
|
|
|
588 | (1) |
|
Biomarkers of Toxic Solvent and Gas Exposure |
|
|
589 | (5) |
|
Biomarkers of Effects of Toxic Solvent and Gas Exposure |
|
|
594 | (1) |
|
Interpretation and Use of Biomonitoring Data |
|
|
594 | (1) |
|
Concluding Remarks and Future Directions |
|
|
594 | (1) |
|
|
|
595 | (6) |
| IV Biotoxins Biomarkers |
|
|
35 Freshwater Cyanotoxins |
|
|
|
|
|
|
|
601 | (1) |
|
|
|
602 | (6) |
|
|
|
608 | (2) |
|
Concluding Remarks and Future Directions |
|
|
610 | (1) |
|
|
|
611 | (4) |
|
|
|
|
|
|
|
|
|
|
615 | (1) |
|
|
|
616 | (2) |
|
|
|
618 | (1) |
|
|
|
618 | (2) |
|
|
|
620 | (2) |
|
Deoxynivalenol Trichothecene |
|
|
622 | (1) |
|
|
|
622 | (1) |
|
Concluding Remarks and Future Directions |
|
|
623 | (1) |
|
|
|
623 | (4) |
|
37 Poisonous Plants: Biomarkers for Diagnosis |
|
|
|
|
|
|
|
|
|
|
|
627 | (1) |
|
Astragalus and Oxytropis Species (Locoweeds, Nitrotoxin spp., and Selenium Accumulators) |
|
|
628 | (5) |
|
Larkspurs (Delphinium spp.) |
|
|
633 | (2) |
|
|
|
635 | (3) |
|
Poison Hemlock (Conium maculatum) |
|
|
638 | (1) |
|
Water Hemlock (Cicuta spp.) |
|
|
639 | (1) |
|
Ponderosa Pine Needles (Pinus spp.) |
|
|
640 | (2) |
|
Rayless Goldenrod (Isocoma pluriflora) |
|
|
642 | (1) |
|
Halogeton (Halogeton glomeratus) |
|
|
643 | (1) |
|
Pyrrolizidine Alkaloid-Containing Plants |
|
|
644 | (2) |
|
|
|
646 | (1) |
|
|
|
647 | (1) |
|
Knapweeds: Centaurea spp. |
|
|
648 | (1) |
|
Concluding Remarks and Future Directions |
|
|
649 | (1) |
|
|
|
650 | (5) |
| V Pharmaceuticals And Nutraceuticals Biomarkers |
|
|
38 Biomarkers of Drug Toxicity and Safety Evaluation |
|
|
|
|
|
Maria Rosa Martinez-Larraiaga |
|
|
|
|
|
|
|
|
655 | (1) |
|
Clinical Drug Development |
|
|
656 | (2) |
|
Integration and Use of Safety Biomarkers in Drug Development |
|
|
658 | (2) |
|
Traditional Indicator for Drug Toxicity Assessment |
|
|
660 | (3) |
|
Biomarkers of Drug Liver Toxicity |
|
|
663 | (6) |
|
Biomarker of Drug-Induced Kidney Toxicity |
|
|
669 | (1) |
|
Biomarkers of Drug-Induced Vascular Injury |
|
|
670 | (2) |
|
Biomarkers of Drug-Induced Cardiac Injury |
|
|
672 | (1) |
|
Biomarkers of Drug-Induced Brain Injury |
|
|
673 | (1) |
|
Biomarkers in Drug Safety Evaluation |
|
|
674 | (13) |
|
Concluding Remarks and Future Directions |
|
|
687 | (1) |
|
|
|
687 | (6) |
|
39 Risk Assessment, Regulation, and the Role of Biomarkers for the Evaluation of Dietary Ingredients Present in Dietary Supplements |
|
|
|
|
|
|
|
|
|
|
|
693 | (2) |
|
Overview of Regulation of Dietary Supplements in the United States |
|
|
695 | (5) |
|
Biomarkers of Toxicity: Dietary Ingredients |
|
|
700 | (5) |
|
Biomarkers of Toxicity: New Dietary Ingredients |
|
|
705 | (1) |
|
Biomarkers of Toxicity: New Dietary Ingredients |
|
|
706 | (2) |
|
Biomarkers of Toxicity: New Dietary Ingredients |
|
|
708 | (2) |
|
Concluding Remarks and Future Directions |
|
|
710 | (2) |
|
|
|
712 | (3) |
|
40 Nutriphenomics in Rodent Models: Impact of Dietary Choices on Toxicological Biomarkers |
|
|
|
|
|
|
|
|
|
715 | (1) |
|
|
|
715 | (3) |
|
Diet-Induced Metabolic Disorders |
|
|
718 | (5) |
|
Potential Effects of Grain-Based Diets and Low-Fat Purified Diets on the Rodent Phenotype |
|
|
723 | (3) |
|
Concluding Remarks and Future Directions |
|
|
726 | (1) |
|
|
|
727 | (8) |
| VI Nanomaterials And Radiation |
|
|
41 Engineered Nanomaterials: Biomarkers of Exposure and Effect |
|
|
|
|
|
|
|
|
|
|
|
Introduction and Background |
|
|
735 | (2) |
|
Classification and Characteristics of Nanomaterials |
|
|
737 | (1) |
|
Definition and Meaning of Biological Monitoring and Its Application to Engineered Nanomaterials |
|
|
738 | (3) |
|
Biological Interactions Relevant to Biomarkers of Exposure to Engineered Nanomaterials at Molecular, Cellular, and Organ Level |
|
|
741 | (8) |
|
Concluding Remarks and Future Directions |
|
|
749 | (1) |
|
|
|
750 | (1) |
|
|
|
750 | (7) |
|
42 Biomarkers of Exposure and Responses to Ionizing Radiation |
|
|
|
|
|
|
|
757 | (1) |
|
Key Definitions and Units |
|
|
758 | (1) |
|
Radiation Protection System |
|
|
759 | (1) |
|
Sources of Radiation Exposure |
|
|
760 | (2) |
|
|
|
762 | (9) |
|
Biomonitoring of Exposure to Radiation |
|
|
771 | (9) |
|
|
|
780 | (3) |
|
Dedication and Acknowledgments |
|
|
783 | (1) |
|
|
|
783 | (6) |
| VII Carcinogens Biomonitoring And Cancer Biomarkers |
|
|
43 Biomonitoring Exposures to Carcinogens |
|
|
|
|
|
|
|
|
|
789 | (1) |
|
|
|
789 | (3) |
|
|
|
792 | (3) |
|
|
|
795 | (1) |
|
New Scenarios to Assess Exposures and Effects: The Omics Approach |
|
|
795 | (3) |
|
Concluding Remarks and Future Directions |
|
|
798 | (1) |
|
|
|
798 | (9) |
|
44 Genotoxicity Biomarkers: Molecular Basis of Genetic Variability and Susceptibility |
|
|
|
|
|
|
|
Suryanar-Ayana V. Vulimiri |
|
|
|
|
|
|
|
|
807 | (1) |
|
Genotoxic Biomarker Detection Methods |
|
|
808 | (3) |
|
In Vitro and In Vivo Biomarkers of Genotoxicity |
|
|
811 | (3) |
|
Biomarkers and Mechanism of Action |
|
|
814 | (3) |
|
Molecular Basis of Genetic Variability and Susceptibility |
|
|
817 | (2) |
|
Concluding Remarks and Future Directions |
|
|
819 | (1) |
|
|
|
819 | (4) |
|
45 Epigenetic Biomarkers in Toxicology |
|
|
|
|
|
|
|
|
|
823 | (1) |
|
|
|
823 | (2) |
|
|
|
825 | (5) |
|
Polycomb and Trithorax Proteins |
|
|
830 | (1) |
|
|
|
831 | (1) |
|
|
|
832 | (4) |
|
Concluding Remarks and Future Directions |
|
|
836 | (1) |
|
|
|
836 | (5) |
|
46 Risk Factors as Biomarkers of Susceptibility in Breast Cancer |
|
|
|
|
|
|
|
|
|
841 | (1) |
|
|
|
841 | (1) |
|
|
|
841 | (1) |
|
|
|
841 | (2) |
|
|
|
843 | (1) |
|
|
|
844 | (1) |
|
Syndromes Predisposing to Breast Cancer |
|
|
845 | (1) |
|
High Penetrance Genes Predisposing to Breast Cancer |
|
|
845 | (1) |
|
Therapeutic Implications of Genetic Biomarkers |
|
|
846 | (1) |
|
Other Highly Penetrant Breast Cancer Predisposing Genes |
|
|
847 | (1) |
|
Moderate Penetrance Breast Cancer Genes |
|
|
847 | (1) |
|
Low Penetrance Breast Cancer Polygenes |
|
|
847 | (1) |
|
DNA Methylation, Definitions, and Measurement Methods |
|
|
847 | (1) |
|
Impact of Methylation Biomarkers |
|
|
848 | (1) |
|
DNA Methylation Markers and Primary Prevention |
|
|
848 | (1) |
|
DNA Methylation Markers for Secondary Prevention and Early Detection |
|
|
848 | (1) |
|
DNA Methylation Markers and Tertiary Prevention and Role in Prognosis |
|
|
849 | (1) |
|
Male Breast Cancer Susceptibility Factors |
|
|
849 | (1) |
|
|
|
849 | (1) |
|
|
|
849 | (1) |
|
|
|
849 | (1) |
|
Cancer Aggressiveness Risk Factors |
|
|
849 | (1) |
|
Impact of Cancer Aggressiveness Risk Factors for Patient Management and Health Policies |
|
|
850 | (1) |
|
|
|
850 | (5) |
|
47 Pancreatic and Ovarian Cancer Biomarkers |
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
855 | (1) |
|
Currently Used Clinical Biomarkers |
|
|
855 | (2) |
|
|
|
857 | (4) |
|
|
|
861 | (2) |
|
|
|
863 | (1) |
|
Concluding Remarks and Future Directions |
|
|
864 | (1) |
|
|
|
864 | (5) |
|
48 Prostate Cancer Biomarkers |
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
869 | (1) |
|
Screening and Early Detection for Prostate Cancer |
|
|
869 | (1) |
|
Contemporary Clinical Biomarkers in Prostate Cancer |
|
|
870 | (2) |
|
Candidate Biomarkers for Prostate Cancer |
|
|
872 | (6) |
|
Concluding Remarks and Future Directions |
|
|
878 | (1) |
|
|
|
879 | (6) |
| VIII Disease Biomarkers |
|
|
49 Biomarkers of Alzheimer's Disease |
|
|
|
|
|
|
|
885 | (1) |
|
Genetic Risk Factors for Alzheimer's Disease |
|
|
886 | (1) |
|
Mechanisms of Synaptic Dysfunction and Neuronal Loss |
|
|
887 | (1) |
|
|
|
888 | (4) |
|
Concluding Remarks and Future Directions |
|
|
892 | (1) |
|
|
|
892 | (3) |
|
50 Biomarkers of Parkinson's Disease |
|
|
|
|
|
|
|
|
|
|
|
|
|
895 | (1) |
|
|
|
895 | (1) |
|
|
|
896 | (2) |
|
|
|
898 | (4) |
|
|
|
902 | (1) |
|
Concluding Remarks and Future Directions |
|
|
902 | (1) |
|
|
|
902 | (1) |
|
|
|
902 | (9) |
|
51 Biomarkers for Drugs of Abuse and Neuropsychiatric Disorders: Models and Mechanisms |
|
|
|
|
|
|
|
|
|
|
|
|
|
911 | (1) |
|
|
|
911 | (1) |
|
|
|
912 | (2) |
|
|
|
914 | (1) |
|
|
|
915 | (1) |
|
|
|
916 | (1) |
|
|
|
917 | (1) |
|
|
|
918 | (3) |
|
Animal Models in Neuropsychiatry |
|
|
921 | (3) |
|
Biomarkers of Bipolar Disorder and Schizophrenia |
|
|
924 | (1) |
|
Biomarkers of Schizophrenia |
|
|
925 | (1) |
|
Concluding Remarks and Future Directions |
|
|
926 | (1) |
|
|
|
927 | (2) |
|
52 Osteoarthritis Biomarkers |
|
|
|
|
|
|
|
|
|
|
|
|
|
929 | (1) |
|
|
|
929 | (1) |
|
Pathophysiology and Signaling Pathways in Osteoarthritis |
|
|
929 | (3) |
|
Classification of Osteoarthritis Biomarkers |
|
|
932 | (1) |
|
Biomarkers of Comfort, Mobility, Function, and Inflammation and Pain |
|
|
932 | (1) |
|
Osteoarthritis Biomarkers in Serum, Synovial Fluid, and Urine |
|
|
933 | (6) |
|
Correlation of Circulatory Biomarkers With Radio-graphic/Imaging Biomarkers and Symptoms of Osteoarthritis |
|
|
939 | (1) |
|
Concluding Remarks and Future Directions |
|
|
939 | (1) |
|
|
|
939 | (1) |
|
|
|
940 | (5) |
|
53 Pathological Biomarkers in Toxicology |
|
|
|
|
|
|
|
|
|
|
|
|
|
945 | (1) |
|
|
|
945 | (8) |
|
|
|
953 | (3) |
|
|
|
956 | (3) |
|
Concluding Remarks and Future Directions |
|
|
959 | (1) |
|
|
|
960 | (3) |
|
54 Oral Pathology Biomarkers |
|
|
|
|
|
|
|
963 | (1) |
|
Anatomical and Histological Considerations of the Oral Cavity |
|
|
963 | (1) |
|
|
|
964 | (3) |
|
Oral Physiology and Pharmacodynamics |
|
|
967 | (1) |
|
Biomarkers in the Oral Cavity |
|
|
967 | (1) |
|
Common Drugs and Toxicants Showing Oral Manifestations |
|
|
968 | (1) |
|
Select Diseases of the Oral Cavity |
|
|
969 | (1) |
|
Oral Biomarkers of Exposure and Effects of Select Drugs/Toxicants |
|
|
969 | (2) |
|
Biomarkers of Select Diseases |
|
|
971 | (1) |
|
|
|
971 | (1) |
|
Immunologically Mediated Oral Diseases |
|
|
971 | (1) |
|
|
|
972 | (1) |
|
|
|
972 | (1) |
|
|
|
973 | (1) |
|
Oral Squamous Cell Carcinoma |
|
|
974 | (1) |
|
Saliva: A Hidden Plethora of Biomarkers |
|
|
975 | (1) |
|
Concluding Remarks and Future Directions |
|
|
976 | (1) |
|
|
|
977 | (4) |
| IX Special Topics |
|
|
55 Biomarkers of Mitochondrial Dysfunction and Toxicity |
|
|
|
|
|
|
|
|
|
|
|
|
|
981 | (1) |
|
Mitochondrial Function: General Overview |
|
|
981 | (1) |
|
|
|
982 | (1) |
|
Xenobiotics and Mitochondrial Dysfunction |
|
|
983 | (1) |
|
|
|
984 | (1) |
|
Mitochondrial Dysfunction in Diabetes |
|
|
984 | (3) |
|
Mitochondrial Dysfunction in Ischemia/Reperfusion |
|
|
987 | (3) |
|
Mitochondrial Dysfunction in Cancer |
|
|
990 | (2) |
|
Concluding Remarks and Future Directions |
|
|
992 | (1) |
|
|
|
992 | (5) |
|
56 Biomarkers of Blood-Brain Barrier Dysfunction |
|
|
|
|
|
|
|
|
|
997 | (1) |
|
Structure and Function of Brain Barriers |
|
|
997 | (2) |
|
In Vivo and In Vitro Models to Study the Blood- Brain Barrier |
|
|
999 | (1) |
|
Toxicants Affecting the Central Nervous System Barriers |
|
|
1000 | (3) |
|
|
|
1003 | (1) |
|
|
|
1004 | (1) |
|
|
|
1005 | (1) |
|
Drugs of Abuse and Therapeutic Drugs |
|
|
1005 | (1) |
|
Neurodegenerative Diseases and Other Conditions |
|
|
1006 | (2) |
|
Concluding Remarks and Future Directions |
|
|
1008 | (1) |
|
|
|
1008 | (1) |
|
|
|
1008 | (5) |
|
57 Biomarkers of Oxidative/Nitrosative Stress and Neurotoxicity |
|
|
|
|
|
|
|
|
|
|
|
1013 | (1) |
|
Lipid Peroxidation and Markers of Oxidative Stress |
|
|
1014 | (1) |
|
Prostaglandin-Like Compounds as In Vivo Markers of Oxidative Stress |
|
|
1014 | (1) |
|
Aldehydes as Lipid Peroxidation Products |
|
|
1015 | (2) |
|
Reactivity of Lipid Peroxidation Products |
|
|
1017 | (1) |
|
Excitotoxicity and Oxidative Damage |
|
|
1017 | (3) |
|
Neuroinflammation and Oxidative Injury |
|
|
1020 | (1) |
|
Metal Toxicity and Oxidative Injury |
|
|
1021 | (1) |
|
|
|
1022 | (3) |
|
|
|
1025 | (1) |
|
Concluding Remarks and Future Directions |
|
|
1026 | (1) |
|
|
|
1026 | (7) |
|
58 Cytoskeletal Disruption as a Biomarker of Developmental Neurotoxicity |
|
|
|
|
|
|
|
|
|
|
|
1033 | (1) |
|
|
|
1033 | (3) |
|
|
|
1036 | (3) |
|
|
|
1039 | (2) |
|
Concluding Remarks and Future Directions |
|
|
1041 | (1) |
|
|
|
1042 | (5) |
|
59 MicroRNA Expression as an Indicator of Tissue Toxicity and a Biomarker in Disease and Drug-Induced Toxicological Evaluation |
|
|
|
|
|
|
|
|
|
|
|
|
|
1047 | (1) |
|
Regulatory Mechanisms of miRNA Biogenesis |
|
|
1047 | (2) |
|
Standard Toxicity Measurements (Tissue and Circulating Biomarkers) |
|
|
1049 | (1) |
|
|
|
1049 | (1) |
|
|
|
1049 | (1) |
|
|
|
1049 | (1) |
|
|
|
1049 | (1) |
|
|
|
1050 | (1) |
|
|
|
1050 | (1) |
|
|
|
1050 | (1) |
|
|
|
1051 | (1) |
|
|
|
1051 | (1) |
|
|
|
1052 | (2) |
|
Kinetics and Pharmacokinetics/Pharmacodynamics |
|
|
1054 | (1) |
|
MiRNA Biomarkers of Toxicity in Organ Systems |
|
|
1054 | (1) |
|
|
|
1054 | (6) |
|
miRNAs as Biomarkers of Pancreatic Toxicity |
|
|
1060 | (1) |
|
|
|
1061 | (1) |
|
|
|
1062 | (2) |
|
|
|
1064 | (1) |
|
|
|
1064 | (3) |
|
Environmental Exposure and miRNA |
|
|
1067 | (1) |
|
Role of miRNA in Arsenic-Induced Carcinogenesis |
|
|
1067 | (2) |
|
Concluding Remarks and Future Directions |
|
|
1069 | (1) |
|
|
|
1069 | (4) |
|
60 Citrulline: Pharmacological Perspectives and Role as a Biomarker in Diseases and Toxicities |
|
|
|
|
|
|
|
|
|
1073 | (1) |
|
|
|
1074 | (1) |
|
Citrulline or Arginine Supplementation |
|
|
1075 | (1) |
|
Salient Aspects of Nitric Oxide |
|
|
1076 | (1) |
|
|
|
1076 | (1) |
|
Pharmacokinetics and Pharmacodynamics of Citrulline |
|
|
1077 | (12) |
|
Concluding Remarks and Future Directions |
|
|
1089 | (1) |
|
|
|
1090 | (7) |
| X Applications Of Biomarkers In Toxicology |
|
|
61 Analysis of Toxin- and Toxicant-Induced Biomarker Signatures Using Microarrays |
|
|
|
|
|
|
|
Biomarkers and Biomarker Signatures in Disease: a Variety of Marker Classes and Possible Inferences |
|
|
1097 | (1) |
|
Selecting Sample Sources for the Measurement of Biomarkers |
|
|
1098 | (1) |
|
Individual Biomarkers and Aggregated Biomarker Signatures |
|
|
1099 | (1) |
|
Approaches to Biomarker Signature Characterization |
|
|
1099 | (1) |
|
Multiplexed High Content Solid Phase Immunoassays |
|
|
1099 | (1) |
|
Flow Cytometry and Fluorescence-Activated Cell Sorting |
|
|
1100 | (1) |
|
Immunohistochemistry and Tissue Microarrays |
|
|
1101 | (1) |
|
Mass Spectrometry Analysis |
|
|
1101 | (1) |
|
Grating-Coupled Surface Plasmon Resonance Microarray Analysis |
|
|
1102 | (2) |
|
Biomarker Signatures in the -Omics era |
|
|
1104 | (2) |
|
Concluding Remarks and Future Directions |
|
|
1106 | (1) |
|
|
|
1106 | (1) |
|
Conflict of Interest Declaration |
|
|
1107 | (1) |
|
|
|
1107 | (4) |
|
62 Biomarkers Detection for Toxicity Testing Using Metabolomics |
|
|
|
|
|
Introduction to Metabolomics |
|
|
1111 | (1) |
|
Metabolomics Experimental Overview |
|
|
1111 | (3) |
|
Applications of Metabolomics Biomarkers in Toxicity Testing |
|
|
1114 | (8) |
|
Concluding Remarks and Future Directions |
|
|
1122 | (1) |
|
|
|
1122 | (3) |
|
63 Transcriptomic Biomarkers in Safety and Risk Assessment of Chemicals |
|
|
1125 | (10) |
|
|
|
|
|
|
|
1125 | (1) |
|
|
|
1125 | (1) |
|
|
|
1126 | (1) |
|
Types of Transcriptomic Biomarkers |
|
|
1127 | (1) |
|
Transcriptomics in Biomarker Discovery |
|
|
1127 | (1) |
|
Cardiovascular Biomarkers |
|
|
1128 | (1) |
|
|
|
1128 | (1) |
|
Biomarkers of Anabolic Agents |
|
|
1128 | (1) |
|
Infectious Agents and Sepsis |
|
|
1129 | (1) |
|
Tobacco and Risk Continuum |
|
|
1130 | (1) |
|
Environmental Chemical Risk Assessment |
|
|
1131 | (1) |
|
Concluding Remarks and Future Directions |
|
|
1131 | (1) |
|
|
|
1131 | (4) |
|
64 Percellome Toxicogenomics Project as a Source of Biomarkers of Chemical Toxicity |
|
|
|
|
|
|
|
1135 | (1) |
|
Materials and Methods for Percellome Data Generation and Example Studies |
|
|
1136 | (3) |
|
Comprehensive Selection of Responding mRNAs |
|
|
1139 | (1) |
|
|
|
1140 | (1) |
|
|
|
1140 | (1) |
|
Merging of TGP Data to Percellome Database |
|
|
1141 | (1) |
|
New Repeated Dosing Study |
|
|
1141 | (1) |
|
|
|
1141 | (7) |
|
Concluding Remarks and Future Directions |
|
|
1148 | (2) |
|
|
|
1150 | (1) |
|
|
|
1150 | (3) |
|
65 Proteomics in Biomarkers of Chemical Toxicity |
|
|
|
|
|
|
|
1153 | (1) |
|
|
|
1154 | (2) |
|
Pesticides and Herbicides |
|
|
1156 | (3) |
|
|
|
1159 | (2) |
|
Concluding Remarks and Future Directions |
|
|
1161 | (1) |
|
|
|
1161 | (4) |
|
66 Biomarkers for Testing Toxicity and Monitoring Exposure to Xenobiotics |
|
|
|
|
|
|
|
|
|
|
|
1165 | (1) |
|
Requirements Expected in a Biomarker for Toxicology Testing and Biomonitoring Xenobiotics Exposure |
|
|
1166 | (2) |
|
Biological Samples Used for Biomonitoring Exposure Through Biomarkers |
|
|
1168 | (1) |
|
Biomarkers of Exposure for Monitoring Xenobiotics Exposure |
|
|
1168 | (2) |
|
Biomarkers of Effect for Toxicology Testing |
|
|
1170 | (2) |
|
Concluding Remarks and Future Directions |
|
|
1172 | (1) |
|
|
|
1173 | (2) |
|
67 Biomarkers in Epidemiology, Risk Assessment and Regulatory Toxicology |
|
|
|
|
|
|
|
|
|
|
|
|
|
1175 | (1) |
|
|
|
1176 | (2) |
|
|
|
1178 | (1) |
|
|
|
1178 | (4) |
|
|
|
1182 | (1) |
|
Cholinesterase Inhibition |
|
|
1182 | (2) |
|
|
|
1184 | (2) |
|
Biomarkers of Susceptibility |
|
|
1186 | (1) |
|
Cancer-Related Biomarkers |
|
|
1187 | (1) |
|
|
|
1187 | (2) |
|
Concluding Remarks and Future Directions |
|
|
1189 | (1) |
|
|
|
1189 | (4) |
| Index |
|
1193 | |
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