Toxicological Effects of Veterinary Medicinal Products in Humans: Volume 2

462 Pages·2012·4.745 MB·English

by  Kevin Woodward, Tim Marrs OBE MD DSc FRCP FRCPath, Mike D Waters, Diana Anderson, Martin F Wilks, Peter Silley, Derek Renshaw

Toxicological Effects of Veterinary Medicinal Products
in Humans
Volume 2
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Issues in Toxicology
Series Editors:
Professor Diana Anderson, University of Bradford, UK
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F Dr Martin F Wilks, University of Basel, Switzerland
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86 Dr Timothy C Marrs, Edentox Associates, Kent, UK
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84 Titles in this Series:
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78 1: Hair in Toxicology: An Important Bio-Monitor
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9/ 2: Male-mediated Developmental Toxicity
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1 3:CytochromeP450:RoleintheMetabolismandToxicityofDrugsandother
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g | d 4: Bile Acids: Toxicology and Bioactivity
or 5: The Comet Assay in Toxicology
sc. 6: Silver in Healthcare
ch 2013p://pubs.r 78:: IEnnSviirliocnomTeonxtiacloCloagryd:ioPlroignyciples and Applications
6 Maron htt 9:BEixopmosaurkreesrsandHumanBiomonitoring,Volume1:OngoingProgramsand
n 012 10:BiomarkersandHumanBiomonitoring,Volume2:SelectedBiomarkersof
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Volume 2
How to obtain future titles on publication:
A standing order plan is available for this series. A standing order will bring
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BookSalesDepartment,RoyalSocietyofChemistry,ThomasGrahamHouse,
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Toxicological Effects of
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86 Preface
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1 The term ‘‘veterinary medicinal product’’ describes those medicines devel-
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d involves an enormous amount of intellectual effort and physical labour as
org | well as a considerable amount of financial investment in order to ensure that
sc. animals have available products that are of the appropriate quality and with
ch 2013p://pubs.r tthhee acnoirmreacltpdaetgierenet aosf weffelelctaisvefnoerstsh.eTuhseesre, pforrodthuectscoanlssuomneeredoftoedibbelesaafneimfoarl
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n 012 with very few exceptions, either are used in human medicine or have been
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most part this means examining their toxicological and pharmacological
properties. However, some veterinary drugs are also microbiologically active,
and this presents certain hazards that also need to be taken into account.
Finally,likehumandrugs,theseproductsalsoeventuallyfindtheirwayintothe
environment. As a result, to examine the potential hazards arising from
veterinary medicine, we need to evaluate their toxicological and pharmacolo-
gical properties, and we need to consider their microbiological properties and
their eventual fate in the natural environment. This latter aspect is of concern
not only because organisms might encounter the remnants of veterinary
medicines as a result of environmental contamination, but also because of the
potentialeffectsforhumanhealthfromthecontaminationoflandanddrinking
IssuesinToxicologyNo.15
ToxicologicalEffectsofVeterinaryMedicinalProductsinHumans:Volume2
ByKevinN.Woodward
rTheRoyalSocietyofChemistry2013
PublishedbytheRoyalSocietyofChemistry,www.rsc.org
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vi Preface
water. I have tried to reach a balance, and review the main issues that might
impactonhumansafetyarisingfromtheuseofveterinarymedicinalproducts.
Itisnotpossibletocovereveryproductordruginaworkofthisnature,andI
havemadenoattempttodoso.Someproductsareusedinfrequently,andsome
05 areonlyusedincertaincountries.Manyothersarehumandrugsthatareused
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FP off-labelinanimals.Ihaveattemptedtocoverthemajordrugclassesaswellas
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6 someindividualdrugsofinterest.Someofthesearenowofhistoricalinterestas
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3 manyhavefallenoutofuseorhavebeenreplacedwithmoreeffectiveandsafer
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4 alternatives.Nevertheless,itwouldberemisstoavoiddiscussionofthesewhere
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9/9 I would like to thank the authors who have invested significant efforts by
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10. fessor Peter Silley. Iwould also like to thankmy family – and dogs–for their
doi: forbearance and patience while I have been working on this project.
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ch 2013p://pubs.r Surrey
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on 0012 1.2.3 Zoonotic Diseases 5
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wnlece 1.2.6 Neoplastic Diseases 6
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Chapter 2 Regulation of Veterinary Medicines 21
2.1 Introduction 21
2.2 Criteria for Evaluation and Authorisation of
Veterinary Medicinal Products 22
2.3 European Union Legislation 24
2.3.1 The National Procedure 25
2.3.2 The Mutual Recognition Procedure 25
2.3.3 The Decentralised Procedure 27
2.3.4 The Centralised Procedure 27
IssuesinToxicologyNo.15
ToxicologicalEffectsofVeterinaryMedicinalProductsinHumans:Volume2
ByKevinN.Woodward
rTheRoyalSocietyofChemistry2013
PublishedbytheRoyalSocietyofChemistry,www.rsc.org
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viii Contents
2.3.5 Maximum Residue Limits 28
2.3.6 Pharmacovigilance 29
2.4 Conclusions 36
References 37
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4.4 Risk Assessment 93
4.5 Risk Management 95
4.6 Risk Communication 96
4.7 Conclusions 97
References 98
Chapter 5 General Anaesthetics 117
5.1 Introduction 117
5.2 Human Health Concerns 118
5.3 Inhalation Anaesthetics 118
5.3.1 Nitrous Oxide 119
5.3.2 Halothane 119
5.3.3 Isoflurane 121
5.3.4 Sevoflurane 123
5.3.5 Enflurane 124
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Contents ix
5.4 Injectable Anaesthetics 124
5.4.1 Propofol 124
5.4.2 Barbiturates 126
5.4.3 Etomidate 127
07 5.4.4 Ketamine 128
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62- References 130
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6.8.1 Toxicity to Humans 181
6.9 Dicyclanil 182
6.10 Cyromazine 184
6.10.1 Effects in Humans 187
6.11 Benzoylureas – Diflubenzuron/Lufenuron/
Teflubenzuron 187
6.12 Spinosad 190
6.13 Macrocyclic Lactones 192
6.13.1 Metabolism 194
6.13.2 Toxicology 195
6.13.3 Summary of Laboratory Animal Toxicity
Studies 198
6.13.4 Factors Affecting Toxicity 199
6.14 Adverse Effects in Target Species 200
6.15 Human Toxicity 202
6.16 Conclusions 203
References 203
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x Contents
Chapter 7 Antineoplastic Drugs 244
7.1 Introduction 244
7.2 Classification of Antineoplastic Drugs 244
07 7.2.1 The Alkylating Agents 245
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8.2.13 Bacitracin 302
8.2.14 Avilamycin 303
8.2.15 Trimethoprim, Baquiloprim and
Sulfonamides 303
8.2.16 Quinoxaline-N-Oxides 306
8.2.17 Other Antibiotic Growth Promoters 308
8.2.18 Nitrofurans 308
8.2.19 Fusidic Acid 310
8.2.20 Novobiocin 310
8.2.21 Rifaximin 311
8.2.22 Dapsone 312
8.2.23 Chlorhexidine 313
8.3 Conclusions 314
References 315
Subject Index 381