Animal feed contamination: Effects on livestock and food safety ISBN 978-1-84569-725-1 The production of animal feed increasingly relies on the global acquisition of feed material, in
Trang 3Animal feed contamination: Effects on livestock and food safety
(ISBN 978-1-84569-725-1)
The production of animal feed increasingly relies on the global acquisition of feed material, increasing the risk of chemical and microbiological contaminants being
transferred into food-producing animals Animal feed contamination provides a
comprehensive overview of recent research into animal feed contaminants and their negative effects on both animal and human health Part I focuses on the contamination of feeds and fodder by microorganisms and animal by-products Analysis of contamination
by persistent organic pollutants and toxic metals follows in Part II, before the problem of natural toxins is considered in Part III Veterinary medicinal products as contaminants are explored in Part IV along with discussion of the use of antimicrobials in animal feed Part
V goes on to highlight the risk from emerging technologies Finally Part VI explores feed safety and quality management by considering the safe supply and management of animal feed, the process of sampling for contaminant analysis and the GMP+ feed safety assurance scheme
Chemical migration and food contact materials
(ISBN 978-1-84569-029-X)
Most food sold is packaged and, although packaging has many positive benefi ts,
constituents from it may migrate into the food, possibly exposing consumers to the chemicals, which may be carcinogenic or genotoxic As demand for pre-packaged food and ready meals increases, the potential for consumer exposure to these chemicals may also increase This collection surveys key research in the area Parts I and II review regulation of food contact materials and the latest developments in analysis of food contact materials and exposure estimation Part III covers different food contact materials
in detail and includes case studies of specifi c packaging types
Endocrine-disrupting chemicals in food
(ISBN 978-1-84569-218-7)
The rise in the incidence of health problems such as reproductive disorders and testicular and breast cancer has been linked by some to endocrine-disrupting chemicals in the environment The role of food in transmitting these chemicals is uncertain and a topic of considerable research This important book addresses key topics in this area Opening chapters review the effects of endocrine-disrupting chemicals on health and behaviour The second part of the book covers the origins, analysis and risk assessment of
endocrine disruptors in food products Concluding chapters concentrate on particular endocrine-disrupting chemicals
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Trang 4Number 235
Chemical contaminants and residues in food
Edited by
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Trang 580 High Street, Sawston, Cambridge CB22 3HJ, UK
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First published 2012, Woodhead Publishing Limited
© Woodhead Publishing Limited, 2012; Chapters 1 and 6 © Crown copyright, 2012
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British Library Cataloguing in Publication Data
A catalogue record for this book is available from the British Library
Library of Congress Control Number: 2012940478
ISBN 978-0-85709-058-4 (print)
ISBN 978-0-85709-579-4 (online)
ISSN 2042-8049 Woodhead Publishing Series in Food Science, Technology and Nutrition (print) ISSN 2042-8057 Woodhead Publishing Series in Food Science, Technology and Nutrition (online) The publisher’s policy is to use permanent paper from mills that operate a sustainable forestry policy, and which has been manufactured from pulp which is processed using acid-free and elemental chlorine-free practices Furthermore, the publisher ensures that the text paper and cover board used have met acceptable environmental accreditation standards
Typeset by Refi neCatch Limited, Bungay, Suffolk, UK
Printed by TJ International Ltd, Padstow, Cornwall, UK
Trang 6Contents
Contributor contact details xiii
Woodhead Publishing Series in Food Science, Technology and Nutrition xvii
Preface xxv
Part I Risk assessment and selected analytical methods 1
1 Risk assessment of chemical contaminants and residues in food 3
D J Benford, Food Standards Agency, UK 1.1 Introduction 3
1.2 Risk assessment 6
1.3 Risk characterisation 11
1.4 Role of risk assessment in risk management 13
1.5 Sources of further information 14
1.6 References 14
2 Gas chromatography and mass spectroscopy techniques for the detection of chemical contaminants and residues in foods 17
P Vazquez-Roig and Y Pico, University of Valencia, Spain 2.1 Introduction 17
2.2 Gas chromatography injection techniques 22
2.3 Gas chromatography separation strategies 27
2.4 Gas chromatography-mass spectrometry detection 31
2.5 Validation of new analytical methods 38
2.6 Applications and future trends 40
2.7 Acknowledgements 52
Trang 72.8 Sources of further information 52
2.9 References 54
3 Applications of HPLC-MS techniques for the analysis of chemical contaminants and residues in food 62
B Cramer and H.-U Humpf, University of Münster, Germany 3.1 Introduction 62
3.2 Ionisation techniques 63
3.3 Mass spectrometer systems 66
3.4 Screening and identifi cation using HPLC-MS 69
3.5 Quantifi cation using HPLC-MS 73
3.6 References 76
4 Cell-based bioassays for the screening of chemical contaminants and residues in foods 79
H Naegeli, University of Zürich, Switzerland 4.1 Introduction 79
4.2 Description of bioassays 80
4.3 Transcriptomics fi ngerprinting technologies 83
4.4 Workfl ow of a transcriptomics fi ngerprinting-based screening strategy 87
4.5 Applications of transcriptomics fi ngerprinting for the screening of chemical contaminants and residues in foods 90
4.6 Conclusion and future trends 91
4.7 Acknowledgements 93
4.8 References 93
4.9 Appendix: Abbreviations 97
Part II Major chemical contaminants of foods 99
5 Dioxins and polychlorinated biphenyls in foods 101
D Schrenk and M Chopra, University of Kaiserslautern, Germany 5.1 Introduction 101
5.2 Properties and occurrence of polychlorinated dibenzo-p-dioxins and dibenzofurans (PCDD/Fs) 102
5.3 Toxicity of polychlorinated dibenzo-p-dioxins and dibenzofurans (PCDD/Fs) 105
5.4 Toxic effects of polychlorinated dibenzo-p-dioxins and dibenzofurans (PCDD/Fs) in humans and experimental animals 108
5.5 Properties and occurrence of polychlorinated biphenyls (PCBs) 114
5.6 Toxicity of polychlorinated biphenyls (PCBs) 118
5.7 References 122
Trang 86 Emerging environmental organic contaminants in foods 124
M Rose and A Fernandes, The Food and Environment Research Agency, UK 6.1 Introduction 124
6.2 Polychlorinated naphthalenes (PCNs) 125
6.3 Brominated fl ame retardants (BFRs) 128
6.4 Polybrominated dibenzo-p-dioxins and furans (PBDD/Fs) 134
6.5 Mixed bromo-chloro dibenzo-p-dioxins and dibenzofurans (PXDD/Fs) and mixed bromo-chloro biphenyls (PXBs) 136
6.6 Perfl uorooctane sulfonic acid (PFOS) and related substances 138
6.7 Conclusion 140
6.8 References 141
7 Veterinary drug residues in foods 148
S Croubels, Ghent University, Belgium and E Daeseleire, Institute for Agricultural and Fisheries Research, Belgium 7.1 Introduction: risk assessment and risk management of veterinary drug residues 148
7.2 Major causes of the presence of drug residues 151
7.3 Group A – residues of substances which have an anabolic effect and unauthorised substances 154
7.4 Group B – residues of veterinary drugs: antibacterial substances 160
7.5 Residues of other veterinary drugs 165
7.6 Analytical methods for drug residue control 169
7.7 Residue monitoring programmes 172
7.8 Bibliography 175
8 Pesticide residues in foods 183
C K Winter, University of California, USA 8.1 Introduction 183
8.2 Regulation of pesticides in food 187
8.3 Pesticide residue monitoring 190
8.4 Risk assessment for pesticide residues in food 195
8.5 Special topics: organic and imported foods 197
8.6 References 199
9 Heat-generated toxicants in foods: acrylamide, MCPD esters and furan 201
R H Stadler, Nestlé Product Technology Centre, Switzerland 9.1 Introduction 201
9.2 Acrylamide in food 202
Trang 99.3 Monochloropropane-1,2-diol (MCPD) esters and
related compounds 212
9.4 Furan in food 219
9.5 Future trends and conclusions 225
9.6 References 225
10 Toxic metals and metalloids in foods 233
A Hartwig and G Jahnke, Karlsruhe Institute of Technology (KIT), Germany 10.1 Introduction 233
10.2 Aluminium in foods 234
10.3 Arsenic in foods 235
10.4 Cadmium in foods 237
10.5 Copper in foods 238
10.6 Iron in foods 240
10.7 Lead in foods 241
10.8 Mercury in foods 243
10.9 Tin in foods 244
10.10 Zinc in foods 245
10.11 Risk assessment of toxic metals and metalloids in foods 247
10.12 References 248
11 Toxicants in foods generated by non-thermal processes 250
M Esselen and D Schrenk, University of Kaiserslautern, Germany 11.1 Introduction 250
11.2 Ethyl carbamate 251
11.3 3-Monochloropropane-1,2-diol and glycidol 258
11.4 Biogenic amines in fermented food 265
11.5 Other examples of toxicants in foods 275
11.6 References 278
12 D -Amino acids and cross-linked amino acids as food contaminants 286
A T Cartus, University of Kaiserslautern, Germany 12.1 Introduction 286
12.2 D-Amino acids in food 287
12.3 Digestibility and utilization of D-amino acids 294
12.4 Toxicokinetics and pharmacological and toxicological properties of individual D-amino acids 296
12.5 Cross-linked amino acids in food 300
12.6 Lysinoalanine contents in food 304
12.7 Nutrition and safety: digestibility, utilization and toxic properties of lysinoalanine and lanthionine 307
Trang 1012.8 Conclusion 309
12.9 References 310
13 Mycotoxins in foods 320
M Rychlik, Technische Universität München, Germany 13.1 Introduction 320
13.2 Mycotoxigenic fungi and mycotoxin occurrence in foods 321
13.3 Toxicity of mycotoxins 326
13.4 Analytical methods for mycotoxins 329
13.5 Regulation of mycotoxins in foods 335
13.6 Future trends 336
13.7 Sources of further information 336
13.8 References 337
14 Phycotoxins and food safety 342
B Luckas, T Krüger and K Röder, University of Jena, Germany 14.1 Introduction 342
14.2 Marine biotoxins 343
14.3 Application of LC-MS/MS methods for determination of assorted marine biotoxins in compliance with legislation 361
14.4 Cyanobacterial toxins 362
14.5 Application of LC-MS/MS methods for determination of assorted cyanobacterial toxins in compliance with legislation 376
14.6 Conclusion 377
14.7 References 378
15 Plant-derived contaminants in food 394
B Dusemund, Federal Institute for Risk Assessment, Germany and A E M F Soffers and I M C M Rietjens, Wageningen University, The Netherlands 15.1 Introduction 394
15.2 Pyrrolizidine alkaloids (PAs) 395
15.3 Ethyl carbamate 398
15.4 Tropane alkaloids (TAs) 400
15.5 Opium alkaloids 402
15.6 Grayanotoxins 405
15.7 Delta-9-tetrahydrocannabinol (THC) 407
15.8 Conclusion and future trends 410
15.9 References 411
15.10 Appendix: Abbreviations 417
Trang 11Part III Contamination of particular foods 419
16 Chemical contamination of cereals 421
A J Alldrick, Campden BRI, UK 16.1 Introduction 421
16.2 Inherent toxicants 426
16.3 Mycotoxins 427
16.4 Heavy metals 430
16.5 Pesticides 433
16.6 Process toxicants 435
16.7 Food additives 438
16.8 Conclusion 439
16.9 Sources of further information and advice 440
16.10 References 440
17 Chemical contamination of red meat 447
M Kim, Animal, Plant and Fisheries Quarantine and Inspection Agency, Republic of Korea 17.1 Introduction 447
17.2 Dioxins (polychlorinated dibenzo- p -dioxins and dibenzofurans, PCDD/Fs) 449
17.3 Polychlorinated biphenyls (PCBs) 452
17.4 Polybrominated diphenyl ethers (PBDEs) 455
17.5 Perfl uorooctane sulfonate (PFOS) and perfl uorooctanoic acid (PFOA) 457
17.6 Pesticides 458
17.7 Toxic metals 459
17.8 Veterinary drugs 461
17.9 Analytical methods for PCDD/Fs, PCBs, and PBDEs 462
17.10 Prevention and regulations of chemical contaminants in red meat 462
17.11 Conclusion 463
17.12 Acknowledgment 463
17.13 References 463
18 Chemical contamination of poultry meat and eggs 469
I Reyes-Herrera and D J Donoghue, University of Arkansas, USA 18.1 Introduction 469
18.2 Unintentional exposure of poultry to chemical contaminants 472
18.3 Veterinary medicines as potential sources of residues in poultry products 477
18.4 Regulation of veterinary drugs in animal food products in the US 481
Trang 1218.5 Future trends 485
18.6 Sources of further information and advice 485
18.7 References 486
19 Contamination of fi nfi sh with persistent organic pollutants and metals 498
M H G Berntssen, A Maage and A.-K Lundebye, National Institute of Nutrition and Seafood Research (NIFES), Norway 19.1 Introduction 498
19.2 Environmental contaminants in fi nfi sh and human exposure 499
19.3 Persistent organic pollutants (POPs) in fi nfi sh 502
19.4 Chlorinated pesticides 503
19.5 Polychlorinated biphenyls 507
19.6 Fluorinated compounds 514
19.7 Metals in feral fi nfi sh 515
19.8 Chemical contaminants in farmed fi nfi sh 518
19.9 References 524
20 Contamination of marine molluscs with heavy metals 535
W.-X Wang, Hong Kong University of Science and Technology (HKUST), Hong Kong 20.1 Introduction 535
20.2 Metals in marine bivalves 536
20.3 Metals in marine gastropods 544
20.4 Bioaccessibility of metals from shellfi sh consumption 547
20.5 Metal contamination in shellfi sh from particular areas 548
20.6 References 549
Appendix: Heat-generated toxicants in foods: heterocyclic aromatic amines 552
A Seidel, Biochemical Institute for Environmental Carcinogens, Germany and W Pfau, GAB Consulting GmbH, Germany A1.1 Introduction 552
A1.2 Formation and nomenclature 553
A1.3 Occurrence and levels of heterocyclic aromatic amines (HAA) in food 554
A1.4 Toxicology 556
A1.5 Carcinogenic activity 559
A1.6 Regulation 561
A1.7 References 561
Index 565
Trang 14Contributor contact details
(* = main contact)
Editor
Professor Dieter Schrenk
Food Chemistry and Toxicology
Chemical Safety Division
Food Standards Agency
E-mail: yolanda.pico@uv.es
Chapter 3
Dr Benedikt Cramer and Professor Dr Hans-Ulrich Humpf* Institute of Food Chemistry
Westfälische Wilhelms-Universität Münster
48149 Müenster Corrensstr 45 Germany E-mail: humpf@uni-muenster.de
Chapter 4
Hanspeter Naegeli Institute of Pharmacology and Toxicology
University of Zürich-Vetsuisse Winterthurerstrasse 260 CH-8057 Zürich Switzerland E-mail: naegelih@vetpharm.uzh.ch
Trang 15University of California One Shields Ave
Davis California 95616 USA
E-mail: ckwinter@ucdavis.edu
Chapter 9
Dr Richard H Stadler Nestlé Product Technology Centre
1350 Orbe Switzerland
E-mail: Richard.stadler@rdor.nestle.com
Chapter 10
Professor Dr Andrea Hartwig* and
Dr Gunnar Jahnke Karlsruhe Institute of Technology (KIT)
Institute of Applied Biosciences Food Chemistry and Toxicology Kaiserstr 12
76131 Karlsruhe Germany
Trang 16Research Center of Nutrition
and Food Sciences
Chair of Analytical Food
Professor Bernd Luckas,
Dr Thomas Krüger* and
D-14195 Berlin Germany Ans E.M.F Soffers and Prof Dr Ir Ivonne M.C.M Rietjens*
Division of Toxicology Wageningen University Tuinlaan 5
6703 HE Wageningen The Netherlands
E-mail: ivonne.rietjens@wur.nl
Chapter 16
Dr Anton J Alldrick Campden BRI Chipping Campden Gloucestershire, GL55 6LD
UK
E-mail: a.alldrick@campden.co.uk
Chapter 17
Dr MeeKyung Kim Toxicology and Residue Chemistry Division
Animal, Plant and Fisheries Quarantine and Inspection Agency
175 Anyangro Anyangsi Gyeonggido 430-757 Republic of Korea
E-mail: mkim@korea.kr
Chapter 18
Dr Ixchel Reyes-Herrera and Professor Dan J Donoghue*
Trang 17Center of Excellence for Poultry
Dr Marc H.G Berntssen*, Amund
Maage and Anne-Katrine Lundebye
National Institute for Nutrition and
Seafood Research (NIFES)
Division of Life Science
Hong Kong University of Science and
Clearwater Bay Kowloon Hong Kong
E-mail: albrecht.seidel@biu-grimmer.de
Professor Wolfgang Pfau GAB Consulting GmbH Hinter den Hoefen 24
21769 Lamstedt Germany
E-mail: Wolfgang.Pfau@gab-consult.de
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159 In-pack processed foods: improving quality Edited by P Richardson
160 Handbook of water and energy management in food processing Edited by
J Klemeš, R Smith and J.-K Kim
161 Environmentally compatible food packaging Edited by E Chiellini
162 Improving farmed fi sh quality and safety Edited by Ø Lie
163 Carbohydrate-active enzymes Edited by K.-H Park
164 Chilled foods: a comprehensive guide Third edition Edited by M Brown
165 Food for the ageing population Edited by M M Raats, C P G M de Groot and
W A Van Staveren
166 Improving the sensory and nutritional quality of fresh meat Edited by J P Kerry
and D A Ledward
Trang 23167 Shellfi sh safety and quality Edited by S E Shumway and G E Rodrick
168 Functional and speciality beverage technology Edited by P Paquin
169 Functional foods: principles and technology M Guo
170 Endocrine-disrupting chemicals in food Edited by I Shaw
171 Meals in science and practice: interdisciplinary research and business
applications Edited by H L Meiselman
172 Food constituents and oral health: current status and future prospects Edited
by M Wilson
173 Handbook of hydrocolloids Second edition Edited by G O Phillips and P A
Williams
174 Food processing technology: principles and practice Third edition P J Fellows
175 Science and technology of enrobed and fi lled chocolate, confectionery and
bakery products Edited by G Talbot
176 Foodborne pathogens: hazards, risk analysis and control Second edition Edited by
C de W Blackburn and P J McClure
177 Designing functional foods: measuring and controlling food structure
breakdown and absorption Edited by D J McClements and E A Decker
178 New technologies in aquaculture: improving production effi ciency, quality and
environmental management Edited by G Burnell and G Allan
179 More baking problems solved S P Cauvain and L S Young
180 Soft drink and fruit juice problems solved P Ashurst and R Hargitt
181 Biofi lms in the food and beverage industries Edited by P M Fratamico,
B A Annous and N W Gunther
182 Dairy-derived ingredients: food and nutraceutical uses Edited by M Corredig
183 Handbook of waste management and co-product recovery in food processing
Volume 2 Edited by K W Waldron
184 Innovations in food labelling Edited by J Albert
185 Delivering performance in food supply chains Edited by C Mena and G Stevens
186 Chemical deterioration and physical instability of food and beverages Edited by
L H Skibsted, J Risbo and M L Andersen
187 Managing wine quality Volume 1: viticulture and wine quality Edited by
A G Reynolds
188 Improving the safety and quality of milk Volume 1: milk production and
processing Edited by M Griffi ths
189 Improving the safety and quality of milk Volume 2: improving quality in milk
products Edited by M Griffi ths
190 Cereal grains: assessing and managing quality Edited by C Wrigley and
193 Winemaking problems solved Edited by C E Butzke
194 Environmental assessment and management in the food industry Edited by
U Sonesson, J Berlin and F Ziegler
195 Consumer-driven innovation in food and personal care products Edited by
S R Jaeger and H MacFie
196 Tracing pathogens in the food chain Edited by S Brul, P.M Fratamico and
T.A McMeekin
Trang 24197 Case studies in novel food processing technologies: innovations in processing,
packaging, and predictive modelling Edited by C J Doona, K Kustin and
F E Feeherry
198 Freeze-drying of pharmaceutical and food products T.-C Hua, B.-L Liu and
H Zhang
199 Oxidation in foods and beverages and antioxidant applications Volume 1:
understanding mechanisms of oxidation and antioxidant activity Edited by
E A Decker, R J Elias and D J McClements
200 Oxidation in foods and beverages and antioxidant applications Volume 2:
management in different industry sectors Edited by E A Decker, R J Elias and
D J McClements
201 Protective cultures, antimicrobial metabolites and bacteriophages for food and
beverage biopreservation Edited by C Lacroix
202 Separation, extraction and concentration processes in the food, beverage and
nutraceutical industries Edited by S S H Rizvi
203 Determining mycotoxins and mycotoxigenic fungi in food and feed Edited by
S De Saeger
204 Developing children’s food products Edited by D Kilcast and F Angus
205 Functional foods: concept to product Second edition Edited by M Saarela
206 Postharvest biology and technology of tropical and subtropical fruits Volume 1:
fundamental issues Edited by E M Yahia
207 Postharvest biology and technology of tropical and subtropical fruits Volume 2:
açai to citrus Edited by E M Yahia
208 Postharvest biology and technology of tropical and subtropical fruits Volume 3:
cocona to mango Edited by E M Yahia
209 Postharvest biology and technology of tropical and subtropical fruits Volume 4:
mangosteen to white sapote Edited by E M Yahia
210 Food and beverage stability and shelf life Edited by D Kilcast and P Subramaniam
211 Processed Meats: improving safety, nutrition and quality Edited by J P Kerry
and J F Kerry
212 Food chain integrity: a holistic approach to food traceability, safety, quality and
authenticity Edited by J Hoorfar, K Jordan, F Butler and R Prugger
213 Improving the safety and quality of eggs and egg products Volume 1 Edited by
Y Nys, M Bain and F Van Immerseel
214 Improving the safety and quality of eggs and egg products Volume 2 Edited by
F Van Immerseel, Y Nys and M Bain
215 Animal feed contamination: effects on livestock and food safety Edited by
J Fink-Gremmels
216 Hygienic design of food factories Edited by J Holah and H L M Lelieveld
217 Manley’s technology of biscuits, crackers and cookies Fourth edition Edited by
D Manley
218 Nanotechnology in the food, beverage and nutraceutical industries Edited by
Q Huang
219 Rice quality: a guide to rice properties and analysis K R Bhattacharya
220 Advances in meat, poultry and seafood packaging Edited by J P Kerry
221 Reducing saturated fats in foods Edited by G Talbot
222 Handbook of food proteins Edited by G O Phillips and P A Williams
223 Lifetime nutritional infl uences on cognition, behaviour and psychiatric illness
Edited by D Benton
Trang 25224 Food machinery for the production of cereal foods, snack foods and
confectionery L.-M Cheng
225 Alcoholic beverages: sensory evaluation and consumer research Edited by
J Piggott
226 Extrusion problems solved: food, pet food and feed M N Riaz and G J Rokey
227 Handbook of herbs and spices Second edition Volume 1 Edited by K V Peter
228 Handbook of herbs and spices Second edition Volume 2 Edited by K V Peter
229 Breadmaking: improving quality Second edition Edited by S P Cauvain
230 Emerging food packaging technologies: principles and practice Edited by
K L Yam and D S Lee
231 Infectious disease in aquaculture: prevention and control Edited by B Austin
232 Diet, immunity and infl ammation Edited by P C Calder and P Yaqoob
233 Natural food additives, ingredients and fl avourings Edited by D Baines and
R Seal
234 Microbial decontamination in the food industry: novel methods and
applications Edited by A Demirci and M O Ngadi
235 Chemical contaminants and residues in foods Edited by D Schrenk
236 Robotics and automation in the food industry: current and future technologies
239 Encapsulation technologies and delivery systems for food ingredients and
nutraceuticals Edited by N Garti and D J McClements
240 Case studies in food safety and authenticity Edited by J Hoorfar
Trang 26Preface
Food safety is a permanent challenge for scientists, advisory boards, regulators, risk managers, local and regional authorities and consumers alike The great importance of safe food is illustrated by the enormous political, social and economic role of food production and manufacturing worldwide For many countries export of marketable food is a cornerstone of their economic survival
In developed countries, the demand for higher-quality food, for an ever broader variety of products from all corners of the world, and the hope for health benefi ts from consumption of ‘healthy’ food have put the topic of food contaminants in the public eye
The vast literature published in recent decades in the fi eld of chemical analysis, however, has increased the prominence of the problem of interpretation of positive analytical data relating to unwanted chemicals Contaminants represent a major subgroup of unwanted food constituents They comprise environmental chemicals, production-related compounds and residues This book aims to cover the various aspects of chemical contamination of food, including cutting-edge analytical methods and modern approaches to risk assessment
The longest section of the book covers the various groups of contaminants, including those formed during food processing The case of acrylamide has alerted the scientifi c community, politicians and the public to the problem of the generation
of unwanted compounds during traditional and novel food production processes Intensive agricultural production of plants and animals is tightly linked to the issue of residues of plant protection chemicals and veterinary drugs The issue of contaminants in animal feed is also of enormous importance, and a broad spectrum
of political measures has been put in place to control this area more strictly Moreover, nature is not innocuous in terms of generation of chemicals with a relevant risk to humans Even in traditional food, natural constituents are present
Trang 27which, if applied in isolated form to laboratory animals, can induce adverse effects, including cancer The hazard generated by the presence of microbial toxins in food is well known and has led to enormous efforts to analyse and minimize their occurrence
Special food categories are the subject of the fi nal section of the book They have their own scenarios of contamination, which, in many instances, are the subject of expert knowledge It is a major aim of this book to spread this knowledge
to experts in many fi eld of food safety, to interested scientists of other disciplines and to students Even the informed consumer may benefi t from a number of more general chapters
It was my privilege to gather a number of outstanding scientists from various parts of the world willing to contribute to this book In particular, I express my thanks to Woodhead Publishing for the outstanding efforts in compiling all contributions and bringing the book into its present shape
Hopefully, this book may help to clarify various important aspects of risk assessment methodologies and the meaning of concentrations, levels and exposures intrinsic to the chemical nature of our food items and their unwanted constituents
D Schrenk
Trang 281
Risk assessment of chemical contaminants and residues in food
D J Benford, Food Standards Agency, UK
Abstract: This chapter describes the approaches used in assessment of risks associated
with chemical contaminants and residues of plant protection products and veterinary drugs in food Risk assessment consists of the interlinked stages of hazard identifi cation, hazard characterisation, exposure assessment and risk characterisation Depending on the completeness of the toxicological database and the properties of a specifi c chemical, the aim is to set health-based guidance values, representing intakes judged to be without appreciable risk, or to identify margins of exposure between reference points associated with the dose–response curve and estimated human dietary exposure The impact of chemical risk on the process of risk management varies depending on the regulatory context
Key words: risk assessment, chemical contaminants, residues, pesticides, veterinary
drugs
1.1 Introduction
Chemical risk assessment provides the scientifi c basis for decisions aimed
at ensuring, maintaining and improving the safety of human exposure to chemicals This chapter describes the approaches used in assessment of risks associated with chemical contaminants and residues of plant protection products and veterinary drugs in food The risk assessments that underpin development of regulatory measures for these chemicals in food are generally conducted by authoritative independent committees of scientifi c experts, such as the scientifi c panels of the European Food Safety Authority (EFSA), and the bodies that advise the Food and Agriculture Organisation (FAO) and World Health Organization (WHO) of the United Nations, i.e the Joint FAO/WHO Expert Committee on Food Additives (JECFA) and the Joint FAO/WHO Meeting on Pesticide Residues (JMPR)
Trang 291.1.1 Risk assessment paradigm and defi nitions
Risk assessment is defi ned as ‘a process intended to calculate or estimate the risk
to a given target organism, system or (sub)population, including the identifi cation
of attendant uncertainties, following exposure to a particular agent, taking into account the inherent characteristics of the agent of concern as well as the characteristics of the specifi c target system’ (IPCS 2009a) In the context of chemicals in food, the term safety assessment is also sometimes used, wherein safety is the ‘practical certainty that adverse effects will not result from exposure
to an agent under defi ned circumstances’ (IPCS 2009a) Risk is defi ned as the
‘probability of an adverse effect in an organism, system or (sub)population caused under specifi ed circumstances by exposure to an agent’ (IPCS 2009a)
The risk assessment is a well-established independent scientifi c process, which, together with risk management and risk communication, constitutes risk analysis (see Fig 1.1 ) It is considered important to separate the activities of risk assessment from those of risk management in order to ensure the scientifi c independence of the assessment, since risk management and communication are also infl uenced by political and socio-economic considerations However, in order
to ensure that the outputs of the risk assessment are useful, it is benefi cial for risk managers to communicate and interact with risk assessors during the process, particularly during the initial problem formulation (also known as framing the question) Thus, the relationship between risk assessment and risk management is
an interactive, often iterative, process
As shown in Fig 1.1 , the risk assessment process consists of four linking steps, relating to hazard, exposure and risk Risk is determined by both the hazard and
Fig 1.1 The risk analysis paradigm
Trang 30the exposure If there is no exposure, then there will be no risk The higher the exposure, the more likely it becomes that there will be a risk In chemical risk assessment, hazard is defi ned as an ‘inherent property of an agent or situation having the potential to cause adverse effects when an organism, system or (sub)population is exposed to that agent’ This differs from microbiological risk assessment, wherein the hazard is generally considered to be the biological agent, rather than its properties There can be a number of different hazards associated with an individual chemical, infl uenced by the route, magnitude and duration of exposure, and the exposed population (e.g different life stages)
1.1.2 Chemical contaminants and residues in food
Chemical contaminants in food can be defi ned as environmental contaminants, which transfer from the environment into the food chain, or as process contaminants, which are generated in food as a result of chemical reactions occurring during cooking and processing Food contact materials can also be a source of chemicals (e.g formaldehyde, melamine, phthalates and primary aromatic amines) with the potential to leach into food Environmental contaminants include ubiquitous pollutants such as dioxins and heavy metals To some extent these may be naturally present in the environment, but they can also be increased
by anthropogenic activity Contaminants can also arise from toxins produced
by fungi (e.g afl atoxins, fumonisins, ochratoxin A), plants (e.g pyrrolizidine alkaloids) and algae (e.g saxitoxins, okadeic acid)
Process contaminants generated during cooking include acrylamide, furan and heterocyclic amines Other processes leading to formation of contaminants include fermentation (e.g ethyl carbamate, 3-monochloropropanediol) and disinfection (e.g trihalomethanes)
Some chemical contaminants are not readily categorised: for example, polycyclic aromatic hydrocarbons can be generated during cooking and drying but also present from the environment Aluminium can be present in food naturally, from environmental contamination, from leaching from food contact materials and also due to the use of approved food additives Similarly, nitrate is produced naturally in plants, but can also be a contaminant and an approved food additive Contaminants
do not have a function in food or food production, and their presence may be considered undesirable However, they are often unavoidable, and found in wide ranges of foods as a result of increasingly sensitive methods of analytical detection The term ‘residues’ is applied to plant protection products (e.g agricultural pesticides) or veterinary drugs in food products Clearly these have a purpose in food production, and there is much greater potential for controls on their conditions
of use, and hence their presence in food
The generic risk assessment approach is appropriate for all types of contaminants and residues The key difference is the availability of data Plant protection products and veterinary drugs are subject to approval processes requiring the manufacturers to provide a dossier that includes toxicological studies conducted to approved guidelines and standards For contaminants, there is
Trang 31generally no sponsor to provide a complete toxicological dataset, and studies published in the scientifi c literature have often been conducted using protocols that limit their applicability for risk assessment purposes (e.g lack of dose–response data) However, epidemiological data are sometimes available, allowing the risk assessment to be based on human data
1.2 Risk assessment
1.2.1 Hazard identifi cation
The aim of hazard identifi cation is to establish the type and nature of adverse effects that an agent has an inherent capacity to cause in an organism, system or (sub)population
An adverse effect is ‘a change in the morphology, physiology, growth, development, reproduction or lifespan of an organism, system or (sub)population that results in an impairment of functional capacity, an impairment of the capacity
to compensate for additional stress or an increase in susceptibility to other infl uences’ (IPCS 2009a)
Hazard identifi cation generally involves a wide range of toxicological tests to defi ne the potential for harm to arise (irrespective of dose) at different stages of the life cycle These tests involve single and repeat dose exposure and aim to identify adverse effects such as general systemic toxicity, effects on the reproductive, immune, endocrine and nervous systems, and tumorigenicity Particular importance is frequently attributed to the results of tests for mutagenicity
or genotoxicity Mutagenicity is the potential to induce mutation, i.e a permanent change in the amount or structure of the genetic material of an organism Mutations may involve individual genes, blocks of genes, or the structure or number of whole chromosomes Genotoxicity is a broader term, which also includes endpoints associated with the potential to result in mutation whilst not necessarily refl ecting a permanent change in the genetic material, such as damage to DNA, production of DNA adducts, unscheduled DNA synthesis subsequent to DNA damage, and sister chromatid exchange Mutations of somatic cells are passed to descendent daughter cells, which can lead to cancer when associated with the activation and expression of oncogenes, or the loss or inactivation of tumour suppressor genes Whilst potential carcinogenicity is normally the main focus of mutagenicity testing, mutations in the germ cells may be transferred to the offspring, which may lead to inherited disorders
There is broad consensus that, unless there is evidence to the contrary, chemical substances that are genotoxic and carcinogenic have the potential to cause DNA damage at any level of exposure and that such damage may lead to tumour development (EFSA 2005a; FAO/WHO 2006a) Furthermore, this mode of action
is generally assumed to be relevant to humans (Boobis et al 2006) Such
substances are not authorised for use in food production, although they can be unavoidably present as contaminants in food Examples include acrylamide, afl atoxins, ethylcarbamate and polycyclic aromatic hydrocarbons
Trang 32In contrast, for carcinogens that act by a non-genotoxic mode of action the tumours generally arise subsequent to other effects, such as cytotoxicity, cell proliferation or hormonal effects, for which it may be possible to assume a threshold and/or which may be based on a biological mechanism not relevant to
humans (Boobis et al 2006)
For some food contaminants, human data from epidemiological studies, case studies or outbreaks of ill health provide support for the human relevance of adverse effects observed in animal studies, or even provide the primary basis for hazard identifi cation For example, the recent EFSA and JECFA evaluations of arsenic, cadmium and lead have noted that the data from experimental animals provide evidence for the plausibility of the observations in the epidemiological studies, and the human data were considered suffi cient to use as the basis of the evaluations (EFSA 2009a; 2009b; 2010; FAO/WHO 2011a; 2011b) For contaminants with chronic effects, it is generally not possible to establish a causal link with human illness in the absence of supporting data from experimental animals In contrast, direct associations can be made for chemicals with acute effects Outbreaks of human illness led to the discovery of marine biotoxins responsible for diarrhoeic, paralytic and amnesic shellfi sh poisoning, and the human data have been used as the basis for establishing acute reference doses (ARfDs) (EFSA 2008a; 2008b; 2009c; 2009d)
1.2.2 Hazard characterisation
Hazard characterisation is closely linked to hazard identifi cation This is the qualitative and, wherever possible, quantitative description of the inherent properties of an agent or situation having the potential to cause adverse effects It should, where possible, include a dose–response assessment and its attendant uncertainties This supports identifi cation of the most important adverse effect(s), i.e those occurring at the lowest doses and considered also likely to occur in humans The dose–response relationship(s) for these effects are analysed in order
to defi ne a level that either had no effect in the critical study (e.g no observed adverse effect level, NOAEL) or induced a predetermined level of effect or response, to be used in risk characterisation It also includes consideration of interspecies differences and human variability in the absorption, distribution, metabolism and excretion (toxicokinetics) and in the biological response (toxicodynamics), and the completeness of the database
Health-based guidance values
For chemicals that are not genotoxic, and certain classes of chemicals with a genotoxic mechanism with a demonstrated threshold effect, the aim of hazard characterisation is generally to set a health-based guidance value This is a level
of exposure that is without appreciable risk to health over a defi ned period The term ‘no appreciable risk’ is used because absolute safety, or zero risk, cannot be guaranteed unless it is possible to guarantee zero exposure For plant protection products and veterinary medicines, the common health-based guidance value is
Trang 33the acceptable daily intake (ADI), which is an estimate of the amount of a chemical
in food or drinking water, expressed on a body weight basis, that can be ingested daily over a lifetime without appreciable health risk to the consumer, derived on the basis of all the known facts at the time of the evaluation The term ‘acceptable’
is used because plant protection products and veterinary medicines are subject to
an approval process In addition to, or instead of, the health-based guidance values referring to lifetime exposure, an ARfD is sometimes set for chemicals with the potential to cause effects following short-term exposure The ARfD relates to the amount of a substance in food or drinking water, expressed on a body weight basis, that can be ingested in a period of 24 h or less without appreciable health risk, and can be numerically equal to or greater than the ADI or tolerable daily intake (TDI) If estimated exposure (see Section 1.2.3) is below the relevant health-based guidance value(s) then the product can be approved and is considered acceptable For similar reasons ADIs are also established for food additives In contrast, the term ‘tolerable’ is used for contaminants, since they are not deliberately used in food, but may be unavoidable There are some differences in terminology used by different authorities: for example, the JECFA uses the term
‘provisional’ for contaminants in food, but the TDI and provisional maximum tolerable daily intake (PMTDI) are essentially equivalent to the ADI For contaminants with cumulative properties, a longer reference period is sometimes used, refl ecting the need to average exposure over a long period of time This is generally the (provisional) tolerable weekly intake (PTWI or TWI), but the JECFA has also established provisional tolerable monthly intakes (PTMIs) for dioxins and cadmium, which have very long half-lives in the human body
Uncertainty factors
The approach to setting health-based guidance values is similar, regardless of the actual terminology used, and the following text generally refers to TDI for ease of reading The TDI has traditionally been established by identifying the NOAEL for the relevant effect occurring at lowest doses, and dividing it by uncertainty (safety) factors to allow for variability between species and within the human population
By convention, a default uncertainty factor of 100 has been used Initially, this was an arbitrary decision, but soon became defi ned as comprising two equal components:
sensitivity of humans compared with the animal model, due to slower elimination from the body, greater balance of activation to detoxication reactions and/or greater sensitivity to the toxic effect; and
the possibility that a proportion of the population may be at greater risk because
of differences in toxicokinetics or tissue sensitivity within the human population
The overall uncertainty factor of 100 may be increased if there are important gaps
in the database for a contaminant, e.g the absence of a NOAEL or of long-term
Trang 34animal studies Conversely, if the TDI is based on human data, then the uncertainty factor for interspecies differences is not required
More recently there have been moves to refi ne the uncertainty factor
by subdividing the tenfold factors into factors for the toxicokinetics and toxicodynamics Examination of various databases has indicated a differential split, with greater weight given to toxicokinetic causes of interspecies differences, whereas equal weighting may be given to toxicodynamic and toxicokinetic differences in individual variability ( Fig 1.2 ) If individual data on any of these components were available, they could then be incorporated into the evaluation
by replacement of the appropriate default For example, if information is available indicating that the toxicokinetics of a particular chemical are quantitatively similar
in the experimental animal used to establish the NOAEL and in humans, then the default factor of 4.0 in Fig 1.2 would be replaced by the value of 1 The factors would then be 2.5 for interspecies differences in toxicokinetics and 10 for human variability, giving an overall factor of 25
Analysis of available data indicates that, in general, the default safety factors are appropriate; however, where data on a compound indicate that the defaults are inappropriate (too low or too high), then the subdivision of the factors allows additional data to be used to modify the defaults and introduce compound-specifi c data This approach has more frequently been applied to contaminants than to residues Examples of health-based guidance values using modifi ed uncertainty factors and chemical-specifi c adjustment factors include dioxins and dioxin-like polychlorinated biphenyls (SCF 2001), methylmercury (FAO/WHO 2004) and zearalenone (EFSA 2011c)
The benchmark dose
Recently there has been increasing use of a benchmark dose (BMD) approach
in preference to using the NOAEL in setting health-based guidance values, since it makes more use of the dose–response relationship and provides quantifi cation of the uncertainty and variability in the dose–response data (EFSA 2009e; IPCS 2009b) The BMD is a dose level, derived by statistical modelling of
Fig 1.2 Subdivision of uncertainty factors (from IPCS 2005)
Trang 35dose–response data, associated with a specifi ed low but measurable change
in response, the benchmark response (BMR) The BMR should be in the region
of the low end of the observed dose–response range, since extrapolation outside the range of observation increases the dependence on the statistical models For quantal data, the BMR is an increase in the incidence of a lesion/response compared with the background response The EFSA Scientifi c Committee recommended a default BMR value of 10% extra risk This approach has been taken in recent evaluations of a number of carcinogens based on data from carcinogenicity studies in experimental animals, such as acrylamide and furan (FAO/WHO 2006a; 2011a), and polycyclic aromatic hydrocarbons (EFSA 2008c) However, when human data are used, different BMRs may
be preferred in order to avoid extrapolation outside the observed range of the data The JECFA used BMRs of 0.5 and 5% extra risk when analysing datasets for cancer endpoints from epidemiological studies of arsenic (FAO/WHO 2011a)
For continuous data, the EFSA Scientifi c Committee recommended a default BMR of 5% change in the magnitude of response, but stressed that other values may be preferred based on biological or statistical considerations (EFSA 2009e) For example, BMR values of 1% decrease in intelligence quotient (IQ) and 1% increase in systolic blood pressure, which were both considered to have signifi cant health consequences at the population level, were used (EFSA 2010) A hybrid approach may be preferred for some types of continuous data, whereby the BMR relates to an increased incidence of a magnitude of response considered to be abnormal, as in the EFSA opinion on cadmium (EFSA 2011a)
When using the BMD approach for setting health-based guidance values, the lower confi dence bound of the BMD (the BMDL) is used in place of the NOAEL, applying the same uncertainty factors An advantage of the BMD approach is that
it can be applied to studies that have failed to identify a NOAEL The BMDL can also be used as a reference point for calculating a margin of exposure (MOE); see Section 1.3.2
1.2.3 Exposure assessment
Assessment of exposure to chemicals in food requires information on the occurrence of the chemical in different types of food, and on the amounts of those foods that are consumed by different population groups
Dietary exposure to residues can be assessed for a plant protection product or veterinary drug before it has been approved for use (pre-regulation) or after it has potentially been in the food supply for years (post-regulation) Pre-regulation, chemical concentration data are available or estimated from the manufacturer In the case of pesticide residues, JMPR uses data generated from fi eld trial studies performed under the proposed Good Agricultural Practice For veterinary drugs, the data are derived by JECFA from controlled residue depletion studies carried out in compliance with Good Practice in the Use of Veterinary Drugs (GPVD) Maximum residue levels (MRLs) are also generated from these data, which are
Trang 36then used to check that pesticides and veterinary medicines have been used in accordance with the assessed practices
Post-regulation, and for contaminants, additional chemical concentration data can be obtained from food in the marketplace The available data should be relevant
to the purpose of the risk assessment (e.g some market data may not be suffi cient for acute exposure assessments) There may also be a need to consider particular scenarios for concentrations in food, such as the potential impact of introducing, or changing, regulatory limits (e.g maximum levels, maximum residue levels) Occurrence data for contaminants and residues may be generated by monitoring programmes, targeted surveys or total diet study approaches Monitoring programmes and targeted surveys frequently focus on foods that are expected to contain the chemical of interest, and the results therefore are not representative of levels in food
in general Total diet studies are based on analyses of foods prepared as for consumption and pooled into composite samples Due to the dilution arising from pooling, much lower limits of detection are required than for analysis of individual foods, and they are more often used for ubiquitous contaminants than for residues Consumption data to be used in exposure assessments should cover the general population, as well as critical groups that are vulnerable or are expected to have exposures that are signifi cantly different from those of the general population (e.g infants, children, pregnant women or the elderly) In order for risk assessments to
be conservative, the dietary exposure assessment should be designed in such a way that potential high dietary exposure to a specifi c chemical is not underestimated The methodologies should take into consideration non-average individuals, such
as those who consume large portions of specifi c food items or show loyalty to specifi c foods or brands of food containing the highest concentrations of the chemical of interest If specifi c consumption data for certain foods are not available from, for instance, nutritional surveys, it may be necessary to develop scenarios based on portion sizes, particularly when considering acute exposure for comparison to an ARfD
1.3 Risk characterisation
1.3.1 Chemicals with health-based guidance values
Risk characterisation involves comparison of the results of the exposure assessment with the health-based guidance value if one has been set If the relevant estimates of high-level dietary exposure for different population subgroups are lower than the relevant health-based guidance value (for example, if estimates of chronic dietary exposure are lower than the TWI, or estimates of acute dietary exposure are lower than the ARfD), the result indicates no appreciable risk to health Exceedance of a health-based guidance value by some subgroups does not inevitably indicate that adverse health effects will occur The ADI or TWI is not a threshold for toxic effect, but aims to be health-protective for the most sensitive population The risk assessment should aim to identify the possible impact of exceeding the health-based guidance value, taking into account the nature of the
Trang 37adverse effects seen at the lowest doses and the magnitude and duration of the exceedance
1.3.2 Margin of exposure (MOE) approach
In circumstances where no health-based guidance value has been proposed, it may
be possible to comment on the margin of exposure (MOE) between a reference point from the dose–response relationship in animals or humans and the estimated human dietary exposure Consideration of whether the resulting MOE indicates a health effect depends on whether the chemical is likely to have a threshold mode
of action For chemicals that are not genotoxic, identifi cation of a health-protective MOE is based on the same considerations as identifying the appropriate uncertainty factor for establishing a health-based guidance value Hence, if the reference point was from an animal study, but with some important gaps in the database, then the minimum MOE considered to be health-protective would be typically greater than 100 and possibly up to 10 000 A lower MOE would be considered health-protective if the reference point was based on human data The EFSA CONTAM panel has also considered MOEs based on body burden, e.g for non-dioxin-like polychlorinated biphenyls (EFSA 2005b) and for polybrominated diphenylethers (EFSA 2011c), which obviates the need for allowance for an uncertainty factor for toxicokinetic differences
For chemicals that are genotoxic and carcinogenic, the traditional assumption
is that there may not be a threshold dose and that some degree of risk may exist at any level of exposure Such substances are generally not considered acceptable for use as plant protection products or veterinary drugs, but can be present as unavoidable contaminants Estimation of a dose associated with a defi ned estimate
of risk by extrapolation from the high doses used in animal carcinogenicity studies
to low doses relevant to human dietary exposure can result in very precise estimates that are highly dependent on the statistical model used for extrapolation and subject to considerable uncertainty regarding the shape of the dose–response relationships at doses far below the observed range Risk estimates based on epidemiological data are subject to less extrapolation and uncertainty, but in practice there are extremely few genotoxic carcinogens in food with data suitable for dose–response modelling Afl atoxin is one exception to this (FAO/WHO 1998) Therefore, in the past, risk characterisation advice for substances that are genotoxic and carcinogenic was primarily that the exposure should be as low as reasonably achievable (ALARA) However, this approach does not take into account either human exposure or carcinogenic potency and therefore does not support prioritisation for risk management action Therefore WHO and EFSA have applied an MOE approach (EFSA 2005a; FAO/WHO 2006a) The EFSA Scientifi c Committee considered that an MOE of 10 000 or more, based on a BMDL for a 10% extra risk derived from animal cancer bioassay data, ‘would be
of low concern from a public health point of view and might reasonably be considered as a low priority for risk management actions’ (EFSA 2005a) The JECFA has taken a similar view in its evaluations (FAO/WHO 2006a; 2006b;
Trang 382011a), but there is as yet no universal consensus on the value of an MOE of low concern Furthermore, the magnitude of the MOE gives an indication of the level
of concern, but is not a precise quantifi cation of risk: the larger the MOE, the smaller the potential risk posed by exposure to the compound under consideration, but a carcinogen with an MOE of 1000 cannot be assumed to represent ten times the cancer risk of a different carcinogen with an MOE of 10 000 Particular MOE values are not necessarily directly comparable, due to the uncertainties in the carcinogenicity data and exposure assessments, and it is important for these to be
described in the narrative accompanying the MOE (Benford et al 2010)
1.3.3 Threshold of toxicological concern (TTC)
The threshold of toxicological concern (TTC) has been developed as an approach to risk characterisation for chemicals with minimal available toxicological data and low human exposure The TTC approach defi nes a number of generic exposure values, derived by extrapolation of toxicity data for structurally related chemicals, below
which there is a low probability of adverse effects on human health (Kroes et al 2004; Munro et al 2008) So far the approach has mainly been used for food contact
materials and fl avouring agents, but it also has potential for evaluation of impurities
1.3.4 Combined exposure
There is increasing awareness of the need to consider any risks associated with combined exposure to mixtures of chemicals present in food, including naturally occurring substances as well as contaminants and residues This has been the
focus of considerable risk assessment activity around the world (e.g Boobis et al 2011; COT 2002; EFSA 2008d; Meek et al 2011) It is beyond the scope of this
chapter to consider this issue in detail However, the currently accepted general principles are as follows (based on EC 2011):
combination effects that can be described by dose/concentration addition
evidence is available that exposure to a mixture of such substances is of health concern if the individual chemicals are present at or below their no-effect levels
at medium or high dose levels (relative to the lowest effect levels)
1.4 Role of risk assessment in risk management
Risk assessment provides the scientifi c advice to underpin risk management action, including:
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The risk assessment is not the sole consideration involved in developing regulations, which means that exceeding a regulatory limit does not inevitably entail a risk to the health of the consumer
For residues of plant protection products, MRLs are based on Good Agricultural Practice, even if the risk assessment indicates that higher levels would not result
in appreciable risk For veterinary drugs, good practice considerations are also taken into account However, the determining criterion is that dietary exposure estimates, based on scenarios related to a set ‘food basket’ of products of animal origin, should be below the ADI In the pre-regulation phase, when proposed uses result in potential chronic or acute dietary exposures that exceed relevant health-based guidance values, the dietary exposure estimates may be refi ned, e.g by restricting approved uses For veterinary drugs, residue levels can also be decreased by extending the withdrawal period before slaughter
For chemical contaminants, maximum levels (MLs) are established to be compatible with tolerable intake levels but also based on the lowest level of contamination that can be reasonably achieved without removing the food from the food supply In addition, reliable measurement in the region of the ML must
be feasible
1.5 Sources of further information
EFSA opinions : http://www.efsa.europa.eu/ [accessed 13 April 2012 ]
JECFA procedures and evaluations : http://www.who.int/ipcs/food/jecfa/en/ [accessed
1.6 References
BENFORD , D , BOLGER , P M , CARTHEW , P , COULET , M , DINOVI , M et al ( 2010 ), ‘ Application
of the Margin of Exposure (MOE) approach to substances in food that are genotoxic and
carcinogenic ’, Food Chem Toxicol , 48 ( Supplement 1 ), S2 – S24
BOOBIS , A , BUDINSKY , R , COLLIE , S , CROFTON , K , EMBRY , M et al ( 2011 ), ‘ Critical analysis
of literature on low-dose synergy for use in screening chemical mixtures for risk
assessment ’, Crit Rev Toxicol , 41 ( 5 ), 369 – 383
COT (2002) , UK COMMITTEE ON TOXICITY OF CHEMICALS IN FOOD , CONSUMER PRODUCTS AND THE ENVIRONMENT , Risk Assessment of Mixtures of Pesticides and Similar Substances ,
Trang 40Food Standards Agency , London, UK http://cot.food.gov.uk/cotreports/cotwgreports/ cocktailreport [accessed 13 April 2012 ]
EC ( 2011 ), SCIENTIFIC COMMITTEE ON CONSUMER SAFETY ( SCCS ), SCIENTIFIC COMMITTEE ON HEALTH AND ENVIRONMENTAL RISKS ( SCHER ), SCIENTIFIC COMMITTEE ON EMERGING AND NEWLY IDENTIFIED HEALTH RISKS ( SCENIHR) , Toxicity and Assessment of Chemical Mixtures
(Preliminary Opinion approved for Public Consultation) http://ec.europa.eu/health/
scientifi c_committees/consultations/public_consultations/scher_consultation_06_en.htm [accessed 13 April 2012 ]
EFSA ( 2005 a), ‘ Opinion of the Scientifi c Committee on a request from EFSA related to a harmonised approach for risk assessment of substances which are both genotoxic and
carcinogenic ’, The EFSA Journal , 282 , 1 – 137 http://www.efsa.europa.eu/en/efsajournal/
pub/282.htm [accessed 13 April 2012 ]
pesticides in the frame of Regulation (EC) 396/20052 ’, The EFSA Journal , 704 , 12 – 84
EFSA ( 2009 a), ‘ EFSA Panel on Contaminants in the Food Chain (CONTAM); Scientifi c
Opinion on Arsenic in Food ’, The EFSA Journal , 7 ( 10 ), 1351 (199 pp.) doi:10.2903/j.
efsa.2009.1351 www.efsa.europa.eu [accessed 13 April 2012 ]
EFSA ( 2009 b), ‘ Scientifi c Opinion of the Panel on Contaminants in the Food Chain on a
request from the European Commission on cadmium in food ’, The EFSA Journal , 980 ,
1 – 139 http://www.efsa.europa.eu/en/efsajournal/doc/980.pdf [accessed 13 April 2012 ]
EFSA ( 2009 c), ‘ Scientifi c Opinion of the Panel on Contaminants in the Food Chain on a request from the European Commission on Marine Biotoxins in Shellfi sh – Saxitoxin
Group ’, The EFSA Journal , 1019 , 1 – 76
EFSA ( 2009 e), ‘ Guidance of the Scientifi c Committee on a request from EFSA on the use of
the benchmark dose approach in risk assessment ’, The EFSA Journal , 1150 , 1 – 72
EFSA ( 2010 ), ‘ EFSA Panel on Contaminants in the Food Chain (CONTAM); Scientifi c
Opinion on Lead in Food ’, The EFSA Journal , 8 ( 4 ), 1570 (147 pp.) doi:10.2903/j.
efsa.2010.1570 www.efsa.europa.eu [accessed 13 April 2012 ]
EFSA ( 2011 a), ‘ European Food Safety Authority; Comparison of the Approaches Taken by
EFSA and JECFA to Establish a HBGV for Cadmium ’, The EFSA Journal , 9 ( 2 ), 2006
(28 pp.) doi:10.2903/j.efsa.2011.2006 www.efsa.europa.eu/efsajournal [accessed
13 April 2012 ]
EFSA ( 2011 b), ‘ EFSA Panel on Contaminants in the Food Chain (CONTAM); Scientifi c
Opinion on Polybrominated Diphenyl Ethers (PBDEs) in Food ’, The EFSA Journal ,
9 ( 5 ), 2156 (274 pp.) doi:10.2903/j.efsa.2011.2156 www.efsa.europa.eu/efsajournal [accessed 13 April 2012 ]