Chemical Analysis of Antibiotic Residues in Food
John Wiley & Sons Inc (Verlag)
978-0-470-49042-6 (ISBN)
An insightful exploration of the key aspects concerning the chemical analysis of antibiotic residues in food The presence of excess residues from frequent antibiotic use in animals is not only illegal, but can pose serious health risks by contaminating products for human consumption such as meat and milk. Chemical Analysis of Antibiotic Residues in Food is a single-source reference for readers interested in the development of analytical methods for analyzing antibiotic residues in food. It covers themes that include quality assurance and quality control, antibiotic chemical properties, pharmacokinetics, metabolism, distribution, food safety regulations, and chemical analysis. In addition, the material presented includes background information valuable for understanding the choice of marker residue and target animal tissue to use for regulatory analysis. This comprehensive reference:
Includes topics on general issues related to screening and confirmatory methods
Presents updated information on food safety regulation based on routine screening and confirmatory methods, especially LC-MS
Provides general guidance for method development, validation, and estimation of measurement uncertainty
Chemical Analysis of Antibiotic Residues in Food is written and organized with a balance between practical use and theory to provide laboratories with a solid and reliable reference on antibiotic residue analysis. Thorough coverage elicits the latest scientific findings to assist the ongoing efforts toward refining analytical methods for producing safe foods of animal origin.
JIAN WANG is currently a research scientist leading a research and development unit for the Canadian Food Inspection Agency in Calgary, Alberta. His responsibilities include planning and conducting research projects in method development for antibiotic and pesticide residues in foods using advanced mass spectral analysis techniques such as UPLC/Q-TOF and LC/ESI-MS/MS. He has written over thirty publications for various journals and books. He was most recently awarded the CFIA Science Branch Recognition Award for leading method development on melamine investigation in 2007. JAMES D. MacNEIL retired as head of the Centre for Veterinary Drug Residues of the Canadian Food Inspection Agency in 2007. His recent achievements include receiving the Joint FAO/WHO Expert Committee on Food Additives 50th Anniversary commemorative silver medal awarded in 2006 for services to JECFA; the Public Service of Canada Award of Excellence, a career achievement in 2007; and appointment as scientist emeritus by CFIA in 2008. He is the former scientific editor for "Drugs, Cosmetics, and Forensics" of the Journal of AOAC International and the author of numerous publications on veterinary drug residue analysis. He is currently an adjunct professor in the Department of Chemistry, Saint Mary's University, Halifax, Canada. JACK F. KAY works in the UK Department for Environment, Food and Rural Affairs. He helped draft European Commission Decision 2002/657/EC and, in 2008, introduced joint auditing to this and ISO 17025 standards into a major UK laboratory. He has actively participated in the Codex Committee on Residues of Veterinary Drugs in Food for more than ten years and was appointed an expert advisor on honey to the Food and Agriculture Organization of the United Nations in 2008. Since 2005, he has held an Honorary Senior Research Fellowship in the Department of Mathematics and Statistics at the University of Strathclyde, Scotland.
Preface xv Acknowledgment xvii
Editors xix
Contributors xxi
1 Antibiotics: Groups and Properties 1
Philip Thomas Reeves
1.1 Introduction, 1
1.1.1 Identification, 1
1.1.2 Chemical Structure, 2
1.1.3 Molecular Formula, 2
1.1.4 Composition of the Substance, 2
1.1.5 pKa, 2
1.1.6 UV Absorbance, 3
1.1.7 Solubility, 3
1.1.8 Stability, 3
1.2 Antibiotic Groups and Properties, 3
1.2.1 Terminology, 3
1.2.2 Fundamental Concepts, 4
1.2.3 Pharmacokinetics of Antimicrobial Drugs, 4
1.2.4 Pharmacodynamics of Antimicrobial Drugs, 5
1.2.4.1 Spectrum of Activity, 5
1.2.4.2 Bactericidal and Bacteriostatic Activity, 6
1.2.4.3 Type of Killing Action, 6
1.2.4.4 Minimum Inhibitory Concentration and Minimum Bactericidal Concentration, 7
1.2.4.5 Mechanisms of Action, 7
1.2.5 Antimicrobial Drug Combinations, 7
1.2.6 Clinical Toxicities, 7
1.2.7 Dosage Forms, 8
1.2.8 Occupational Health and Safety Issues, 8
1.2.9 Environmental Issues, 8
1.3 Major Groups of Antibiotics, 8
1.3.1 Aminoglycosides, 8
1.3.2 ß-Lactams, 10
1.3.3 Quinoxalines, 18
1.3.4 Lincosamides, 20
1.3.5 Macrolides and Pleuromutilins, 21
1.3.6 Nitrofurans, 27
1.3.7 Nitroimidazoles, 28
1.3.8 Phenicols, 30
1.3.9 Polyether Antibiotics (Ionophores), 31
1.3.10 Polypeptides, Glycopeptides, and Streptogramins, 35
1.3.11 Phosphoglycolipids, 36
1.3.12 Quinolones, 36
1.3.13 Sulfonamides, 44
1.3.14 Tetracyclines, 45
1.4 Restricted and Prohibited Uses of Antimicrobial Agents in Food Animals, 52
1.5 Conclusions, 52
Acknowledgments, 53
References, 53
2 Pharmacokinetics, Distribution, Bioavailability, and Relationship to Antibiotic Residues 61
Peter Lees and Pierre-Louis Toutain
2.1 Introduction, 61
2.2 Principles of Pharmacokinetics, 61
2.2.1 Pharmacokinetic Parameters, 61
2.2.2 Regulatory Guidelines on Dosage Selection for Efficacy, 64
2.2.3 Residue Concentrations in Relation to Administered Dose, 64
2.2.4 Dosage and Residue Concentrations in Relation to Target Clinical Populations, 66
2.2.5 Single-Animal versus Herd Treatment and Establishment of Withholding Time (WhT), 66
2.2.6 Influence of Antimicrobial Drug (AMD) Physicochemical Properties on Residues and WhT, 67
2.3 Administration, Distribution, and Metabolism of Drug Classes, 67
2.3.1 Aminoglycosides and Aminocyclitols, 67
2.3.2 ß-Lactams: Penicillins and Cephalosporins, 69
2.3.3 Quinoxalines: Carbadox and Olaquindox, 71
2.3.4 Lincosamides and Pleuromutilins, 71
2.3.5 Macrolides, Triamilides, and Azalides, 72
2.3.6 Nitrofurans, 73
2.3.7 Nitroimidazoles, 73
2.3.8 Phenicols, 73
2.3.9 Polyether Antibiotic Ionophores, 74
2.3.10 Polypeptides, 75
2.3.11 Quinolones, 75
2.3.12 Sulfonamides and Diaminopyrimidines, 77
2.3.13 Polymyxins, 79
2.3.14 Tetracyclines, 79
2.4 Setting Guidelines for Residues by Regulatory Authorities, 81
2.5 Definition, Assessment, Characterization, Management, and Communication of Risk, 82
2.5.1 Introduction and Summary of Regulatory Requirements, 82
2.5.2 Risk Assessment, 84
2.5.2.1 Hazard Assessment, 88
2.5.2.2 Exposure Assessment, 89
2.5.3 Risk Characterization, 90
2.5.4 Risk Management, 91
2.5.4.1 Withholding Times, 91
2.5.4.2 Prediction of Withdholding Times from Plasma Pharmacokinetic Data, 93
2.5.4.3 International Trade, 93
2.5.5 Risk Communication, 94
2.6 Residue Violations: Their Significance and Prevention, 94
2.6.1 Roles of Regulatory and Non-regulatory Bodies, 94
2.6.2 Residue Detection Programs, 95
2.6.2.1 Monitoring Program, 96
2.6.2.2 Enforcement Programs, 96
2.6.2.3 Surveillance Programs, 97
2.6.2.4 Exploratory Programs, 97
2.6.2.5 Imported Food Animal Products, 97
2.6.2.6 Residue Testing in Milk, 97
2.7 Further Considerations, 98
2.7.1 Injection Site Residues and Flip-Flop Pharmacokinetics, 98
2.7.2 Bioequivalence and Residue Depletion Profiles, 100
2.7.3 Sales and Usage Data, 101
2.7.3.1 Sales of AMDs in the United Kingdom, 2003–2008, 101
2.7.3.2 Comparison of AMD Usage in Human and Veterinary Medicine in France, 1999–2005, 102
2.7.3.3 Global Animal Health Sales and Sales of AMDs for Bovine Respiratory Disease, 103
References, 104
3 Antibiotic Residues in Food and Drinking Water, and Food Safety Regulations 111
Kevin J. Greenlees, Lynn G. Friedlander, and Alistair Boxall
3.1 Introduction, 111
3.2 Residues in Food—Where is the Smoking Gun?, 111
3.3 How Allowable Residue Concentrations Are Determined, 113
3.3.1 Toxicology—Setting Concentrations Allowed in the Human Diet, 113
3.3.2 Setting Residue Concentrations for Substances Not Allowed in Food, 114
3.3.3 Setting Residue Concentrations Allowed in Food, 114
3.3.3.1 Tolerances, 115
3.3.3.2 Maximum Residue Limits, 116
3.3.4 International Harmonization, 117
3.4 Indirect Consumer Exposure to Antibiotics in the Natural Environment, 117
3.4.1 Transport to and Occurrence in Surface Waters and Groundwaters, 119
3.4.2 Uptake of Antibiotics into Crops, 119
3.4.3 Risks of Antibiotics in the Environment to Human Health, 120
3.5 Summary, 120
References, 121
4 Sample Preparation: Extraction and Clean-up 125
Alida A. M. (Linda) Stolker and Martin Danaher
4.1 Introduction, 125
4.2 Sample Selection and Pre-treatment, 126
4.3 Sample Extraction, 127
4.3.1 Target Marker Residue, 127
4.3.2 Stability of Biological Samples, 127
4.4 Extraction Techniques, 128
4.4.1 Liquid–Liquid Extraction, 128
4.4.2 Dilute and Shoot, 128
4.4.3 Liquid–Liquid Based Extraction Procedures, 129
4.4.3.1 QuEChERS, 129
4.4.3.2 Bipolarity Extraction, 129
4.4.4 Pressurized Liquid Extraction (Including Supercritical Fluid Extraction), 130
4.4.5 Solid Phase Extraction (SPE), 131
4.4.5.1 Conventional SPE, 131
4.4.5.2 Automated SPE, 132
4.4.6 Solid Phase Extraction-Based Techniques, 133
4.4.6.1 Dispersive SPE, 133
4.4.6.2 Matrix Solid Phase Dispersion, 134
4.4.6.3 Solid Phase Micro-extraction, 135
4.4.6.4 Micro-extraction by Packed Sorbent, 137
4.4.6.5 Stir-bar Sorptive Extraction, 137
4.4.6.6 Restricted-Access Materials, 138
4.4.7 Solid Phase Extraction-Based Selective Approaches, 138
4.4.7.1 Immunoaffinity Chromatography, 138
4.4.7.2 Molecularly Imprinted Polymers, 139
4.4.7.3 Aptamers, 140
4.4.8 Turbulent-Flow Chromatography, 140
4.4.9 Miscellaneous, 142
4.4.9.1 Ultrafiltration, 142
4.4.9.2 Microwave-Assisted Extraction, 142
4.4.9.3 Ultrasound-Assisted Extraction, 144
4.5 Final Remarks and Conclusions, 144
References, 146
5 Bioanalytical Screening Methods 153
Sara Stead and Jacques Stark
5.1 Introduction, 153
5.2 Microbial Inhibition Assays, 154
5.2.1 The History and Basic Principles of Microbial Inhibition Assays, 154
5.2.2 The Four-Plate Test and the New Dutch Kidney Test, 156
5.2.3 Commercial Microbial Inhibition Assays for Milk, 156
5.2.4 Commercial Microbial Inhibition Assays for Meat-, Egg-, and Honey-Based Foods, 159
5.2.5 Further Developments of Microbial Inhibition Assays and Future Prospects, 160
5.2.5.1 Sensitivity, 160
5.2.5.2 Test Duration, 161
5.2.5.3 Ease of Use, 161
5.2.5.4 Automation, 161
5.2.5.5 Pre-treatment of Samples, 162
5.2.5.6 Confirmation/Class-Specific Identification, 163
5.2.6 Conclusions Regarding Microbial Inhibition Assays, 164
5.3 Rapid Test Kits, 164
5.3.1 Basic Principles of Immunoassay Format Rapid Tests, 164
5.3.2 Lateral-Flow Immunoassays, 165
5.3.2.1 Sandwich Format, 166
5.3.2.2 Competitive Format, 166
5.3.3 Commercial Lateral-Flow Immunoassays for Milk, Animal Tissues, and Honey, 168
5.3.4 Receptor-Based Radioimmunoassay: Charm II System, 170
5.3.5 Basic Principles of Enzymatic Tests, 171
5.3.5.1 The Penzyme Milk Test, 171
5.3.5.2 The Delvo-X-PRESS, 172
5.3.6 Conclusions Regarding Rapid Test Kits, 174
5.4 Surface Plasmon Resonance (SPR) Biosensor Technology, 174
5.4.1 Basic Principles of SPR Biosensor, 174
5.4.2 Commercially Available SPR Biosensor Applications for Milk, Animal Tissues, Feed, and Honey, 175
5.4.3 Conclusions Regarding Surface Plasmon Resonance (SPR) Technology, 176
5.5 Enzyme-Linked Immunosorbent Assay (ELISA), 178
5.5.1 Basic Principles of ELISA, 178
5.5.2 Automated ELISA Systems, 178
5.5.3 Alternative Immunoassay Formats, 179
5.5.4 Commercially Available ELISA Kits for Antibiotic Residues, 179
5.5.5 Conclusions Regarding ELISA, 180
5.6 General Considerations Concerning the Performance Criteria for Screening Assays, 181
5.7 Overall Conclusions on Bioanalytical Screening Assays, 181
Abbreviations, 182
References, 182
6 Chemical Analysis: Quantitative and Confirmatory Methods 187
Jian Wang and Sherri B. Turnipseed
6.1 Introduction, 187
6.2 Single-Class and Multi-class Methods, 187
6.3 Chromatographic Separation, 195
6.3.1 Chromatographic Parameters, 195
6.3.2 Mobile Phase, 195
6.3.3 Conventional Liquid Chromatography, 196
6.3.3.1 Reversed Phase Chromatography, 196
6.3.3.2 Ion-Pairing Chromatography, 196
6.3.3.3 Hydrophilic Interaction Liquid Chromatography, 197
6.3.4 Ultra-High-Performance or Ultra-High-Pressure Liquid Chromatography, 198
6.4 Mass Spectrometry, 200
6.4.1 Ionization and Interfaces, 200
6.4.2 Matrix Effects, 202
6.4.3 Mass Spectrometers, 205
6.4.3.1 Single Quadrupole, 205
6.4.3.2 Triple Quadrupole, 206
6.4.3.3 Quadrupole Ion Trap, 208
6.4.3.4 Linear Ion Trap, 209
6.4.3.5 Time-of-Flight, 210
6.4.3.6 Orbitrap, 212
6.4.4 Other Advanced Mass Spectrometric Techniques, 214
6.4.4.1 Ion Mobility Spectrometry, 214
6.4.4.2 Ambient Mass Spectrometry, 214
6.4.4.3 Other Recently Developed Desorption Ionization Techniques, 216
6.4.5 Fragmentation, 216
6.4.6 Mass Spectral Library, 216
Acknowledgment, 219
Abbreviations, 220
References, 220
7 Single-Residue Quantitative and Confirmatory Methods 227
Jonathan A. Tarbin, Ross A. Potter, Alida A. M. (Linda) Stolker, and Bjorn Berendsen
7.1 Introduction, 227
7.2 Carbadox and Olaquindox, 227
7.2.1 Background, 227
7.2.2 Analysis, 229
7.2.3 Conclusions, 230
7.3 Ceftiofur and Desfuroylceftiofur, 230
7.3.1 Background, 230
7.3.2 Analysis Using Deconjugation, 231
7.3.3 Analysis of Individual Metabolites, 232
7.3.4 Analysis after Alkaline Hydrolysis, 232
7.3.5 Conclusions, 233
7.4 Chloramphenicol, 233
7.4.1 Background, 233
7.4.2 Analysis by GC-MS and LC-MS, 233
7.4.3 An Investigation into the Possible Natural Occurrence of CAP, 235
7.4.4 Analysis of CAP in Herbs and Grass (Feed) Using LC-MS, 236
7.4.5 Conclusions, 236
7.5 Nitrofurans, 236
7.5.1 Background, 236
7.5.2 Analysis of Nitrofurans, 236
7.5.3 Identification of Nitrofuran Metabolites, 237
7.5.4 Conclusions, 239
7.6 Nitroimidazoles and Their Metabolites, 239
7.6.1 Background, 239
7.6.2 Analysis, 240
7.6.3 Conclusions, 241
7.7 Sulfonamides and Their N4-Acetyl Metabolites, 241
7.7.1 Background, 241
7.7.2 N4-Acetyl Metabolites, 242
7.7.3 Analysis, 243
7.7.4 Conclusions, 244
7.8 Tetracyclines and Their 4-Epimers, 244
7.8.1 Background, 244
7.8.2 Analysis, 245
7.8.3 Conclusions, 246
7.9 Miscellaneous, 246
7.9.1 Aminoglycosides, 246
7.9.2 Compounds with Marker Residues Requiring Chemical Conversion, 247
7.9.2.1 Florfenicol, 247
7.9.3 Miscellaneous Analytical Issues, 250
7.9.3.1 Lincosamides, 250
7.9.3.2 Enrofloxacin, 251
7.9.4 Gaps in Analytical Coverage, 251
7.10 Summary, 252
Abbreviations, 253
References, 254
8 Method Development and Method Validation 263
Jack F. Kay and James D. MacNeil
8.1 Introduction, 263
8.2 Sources of Guidance on Method Validation, 263
8.2.1 Organizations that Are Sources of Guidance on Method Validation, 264
8.2.1.1 International Union of Pure and Applied Chemistry (IUPAC), 264
8.2.1.2 AOAC International, 264
8.2.1.3 International Standards Organization (ISO), 264
8.2.1.4 Eurachem, 265
8.2.1.5 VICH, 265
8.2.1.6 Codex Alimentarius Commission (CAC), 265
8.2.1.7 Joint FAO/WHO Expert Committee on Food Additives (JECFA), 265
8.2.1.8 European Commission, 266
8.2.1.9 US Food and Drug Administration (USFDA), 266
8.3 The Evolution of Approaches to Method Validation for Veterinary Drug Residues in Foods, 266
8.3.1 Evolution of “Single-Laboratory Validation” and the “Criteria Approach,” 266
8.3.2 The Vienna Consultation, 267
8.3.3 The Budapest Workshop and the Miskolc Consultation, 267
8.3.4 Codex Alimentarius Commission Guidelines, 267
8.4 Method Performance Characteristics, 268
8.5 Components of Method Development, 268
8.5.1 Identification of “Fitness for Purpose” of an Analytical Method, 269
8.5.2 Screening versus Confirmation, 270
8.5.3 Purity of Analytical Standards, 270
8.5.4 Analyte Stability in Solution, 271
8.5.5 Planning the Method Development, 271
8.5.6 Analyte Stability during Sample Processing (Analysis), 272
8.5.7 Analyte Stability during Sample Storage, 272
8.5.8 Ruggedness Testing (Robustness), 273
8.5.9 Critical Control Points, 274
8.6 Components of Method Validation, 274
8.6.1 Understanding the Requirements, 274
8.6.2 Management of the Method Validation Process, 274
8.6.3 Experimental Design, 275
8.7 Performance Characteristics Assessed during Method Development and Confirmed during Method Validation for Quantitative Methods, 275
8.7.1 Calibration Curve and Analytical Range, 275
8.7.2 Sensitivity, 277
8.7.3 Selectivity, 277
8.7.3.1 Definitions, 277
8.7.3.2 Suggested Selectivity Experiments, 278
8.7.3.3 Additional Selectivity Considerations for Mass Spectral Detection, 279
8.7.4 Accuracy, 281
8.7.5 Recovery, 282
8.7.6 Precision, 283
8.7.7 Experimental Determination of Recovery and Precision, 283
8.7.7.1 Choice of Experimental Design, 283
8.7.7.2 Matrix Issues in Calibration, 286
8.7.8 Measurement Uncertainty (MU), 287
8.7.9 Limits of Detection and Limits of Quantification, 287
8.7.10 Decision Limit (CCa) and Detection Capability (CCß), 289
8.8 Significant Figures, 289
8.9 Final Thoughts, 289
References, 289
9 Measurement Uncertainty 295
Jian Wang, Andrew Cannavan, Leslie Dickson, and Rick Fedeniuk
9.1 Introduction, 295
9.2 General Principles and Approaches, 295
9.3 Worked Examples, 297
9.3.1 EURACHEM/CITAC Approach, 297
9.3.2 Measurement Uncertainty Based on the Barwick–Ellison Approach Using In-House Validation Data, 302
9.3.3 Measurement Uncertainty Based on Nested Experimental Design Using In-House Validation Data, 305
9.3.3.1 Recovery (R) and Its Uncertainty [u(R)], 306
9.3.3.2 Precision and Its Uncertainty [u(P )], 312
9.3.3.3 Combined Standard Uncertainty and Expanded Uncertainty, 312
9.3.4 Measurement Uncertainty Based on Inter-laboratory Study Data, 312
9.3.5 Measurement Uncertainty Based on Proficiency Test Data, 317
9.3.6 Measurement Uncertainty Based on Quality Control Data and Certified Reference Materials, 319
9.3.6.1 Scenario A: Use of Certified Reference Material for Estimation of Uncertainty, 320
9.3.6.2 Scenario B. Use of Incurred Residue Samples and Fortified Blank Samples for Estimation of Uncertainty, 324
References, 325
10 Quality Assurance and Quality Control 327
Andrew Cannavan, Jack F. Kay, and Bruno Le Bizec
10.1 Introduction, 327
10.1.1 Quality—What Is It?, 327
10.1.2 Why Implement a Quality System?, 328
10.1.3 Quality System Requirements for the Laboratory, 328
10.2 Quality Management, 329
10.2.1 Total Quality Management, 329
10.2.2 Organizational Elements of a Quality System, 330
10.2.2.1 Process Management, 330
10.2.2.2 The Quality Manual, 330
10.2.2.3 Documentation, 330
10.2.3 Technical Elements of a Quality System, 331
10.3 Conformity Assessment, 331
10.3.1 Audits and Inspections, 331
10.3.2 Certification and Accreditation, 332
10.3.3 Advantages of Accreditation, 332
10.3.4 Requirements under Codex Guidelines and EU Legislation, 332
10.4 Guidelines and Standards, 333
10.4.1 Codex Alimentarius, 333
10.4.2 Guidelines for the Design and Implementation of a National Regulatory Food Safety Assurance Program Associated with the Use of Veterinary Drugs in Food-Producing Animals, 334
10.4.3 ISO/IEC 17025:2005, 334
10.4.4 Method Validation and Quality Control Procedures for Pesticide Residue Analysis in Food and Feed (Document SANCO/10684/2009), 335
10.4.5 EURACHEM/CITAC Guide to Quality in Analytical Chemistry, 335
10.4.6 OECD Good Laboratory Practice, 336
10.5 Quality Control in the Laboratory, 336
10.5.1 Sample Reception, Storage, and Traceability throughout the Analytical Process, 336
10.5.1.1 Sample Reception, 336
10.5.1.2 Sample Acceptance, 337
10.5.1.3 Sample Identification, 337
10.5.1.4 Sample Storage (Pre-analysis), 337
10.5.1.5 Reporting, 338
10.5.1.6 Sample Documentation, 338
10.5.1.7 Sample Storage (Post-reporting), 338
10.5.2 Analytical Method Requirements, 338
10.5.2.1 Introduction, 338
10.5.2.2 Screening Methods, 338
10.5.2.3 Confirmatory Methods, 339
10.5.2.4 Decision Limit, Detection Capability, Performance Limit, and Sample Compliance, 339
10.5.3 Analytical Standards and Certified Reference Materials, 339
10.5.3.1 Introduction, 339
10.5.3.2 Certified Reference Materials (CRMs), 340
10.5.3.3 Blank Samples, 341
10.5.3.4 Utilization of CRMs and Control Samples, 341
10.5.4 Proficiency Testing (PT), 341
10.5.5 Control of Instruments and Methods in the Laboratory, 342
10.6 Conclusion, 344
References, 344
Index 347
| Erscheint lt. Verlag | 27.12.2011 |
|---|---|
| Reihe/Serie | Wiley Series on Mass Spectrometry |
| Verlagsort | New York |
| Sprache | englisch |
| Maße | 221 x 287 mm |
| Gewicht | 1075 g |
| Themenwelt | Naturwissenschaften ► Chemie ► Analytische Chemie |
| Technik ► Lebensmitteltechnologie | |
| Weitere Fachgebiete ► Land- / Forstwirtschaft / Fischerei | |
| ISBN-10 | 0-470-49042-X / 047049042X |
| ISBN-13 | 978-0-470-49042-6 / 9780470490426 |
| Zustand | Neuware |
| Haben Sie eine Frage zum Produkt? |
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