Toxicological Effects of Veterinary Medicinal Products in Humans Volume 1, 1st Edition Chapter-by-Chapter Download
Toxicological Effects of Veterinary Medicinal Products in Humans Volume 1, 1st Edition Chapter-by-Chapter Download
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vi Preface
water. I have tried to reach a balance, and review the main issues that might
impact on human safety arising from the use of veterinary medicinal products.
It is not possible to cover every product or drug in a work of this nature, and I
have made no attempt to do so. Some products are used infrequently, and some
Published on 31 December 2012 on http://pubs.rsc.org | doi:10.1039/9781849735483-FP005
are only used in certain countries. Many others are human drugs that are used
off-label in animals. I have attempted to cover the major drug classes as well as
some individual drugs of interest. Some of these are now of historical interest as
many have fallen out of use or have been replaced with more effective and safer
alternatives. Nevertheless, it would be remiss to avoid discussion of these where
they may have impacted human safety in the past, so I have included them here.
I would like to thank the authors who have invested significant efforts by
providing chapters for this book – Dr Tim Marrs, Derek Renshaw and Pro-
fessor Peter Silley. I would also like to thank my family – and dogs – for their
forbearance and patience while I have been working on this project.
Kevin Woodward
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Surrey
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Contents
Volume 1
1.1 Introduction 1
1.2 Physical Injuries 2
1.2.1 Accidents and Related Incidents 2
1.2.2 Needlestick Injuries 4
1.2.3 Zoonotic Diseases 5
1.2.4 Dermatoses 5
1.2.5 Allergies 6
1.2.6 Neoplastic Diseases 6
1.2.7 Specific Risks for Women 7
1.2.8 Mental Health 7
1.3 Conclusions 8
References 8
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
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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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3.1 Introduction 40
3.2 Establishment of MRLs in the EU 41
3.3 MRLs – Other Considerations 46
3.4 The Joint FAO/WHO Expert Committee on
Food Additives (JECFA) 50
3.5 Practical Uses of MRLs 51
3.6 Residues Surveillance 53
3.6.1 Residues and Residues Studies 54
3.6.2 Residues Surveillance for Veterinary Drugs in
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the UK 56
3.7 Residues Avoidance 59
3.8 Conclusions 62
References 63
4.1 Introduction 81
4.2 The Assessment Process 83
4.2.1 Hazard Identification and Assessment 83
4.2.2 Exposure Assessment 86
4.3 Biological Monitoring 92
4.4 Risk Assessment 93
4.5 Risk Management 95
4.6 Risk Communication 96
4.7 Conclusions 97
References 98
9.1 Introduction 1
9.1.1 Coccidiosis, Coccidiostats and Anticoccidial
Medicines 1
9.1.2 Human Exposure 2
9.1.3 Committees that Evaluate the Safety of
Coccidiostats 2
9.2 Approaches Taken to Ensure the Human Safety of
Coccidiostats 2
9.2.1 Consumer Safety 2
9.2.2 User Safety 3
9.2.3 Inconsistencies in the Values of ADIs 3
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10.1 Introduction 33
10.2 Anticholinesterase Activity 38
10.3 Clinical Effects 39
10.3.1 Syndromes Associated with OP
Exposure 39
10.3.2 Other Effects of OPs 44
10.3.3 Diagnostic Tests and Biomarkers 47
10.3.4 Management of OP Poisoning 49
10.4 Exposure and Regulatory Aspects 50
10.4.1 European Union 50
10.4.2 USA 51
10.4.3 Interpretation of Regulatory Studies 51
10.4.4 Pharmacovigilance 52
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xii Contents
10.5 Sheep Dips in the United Kingdom 52
10.5.1 Introduction 52
10.5.2 Treatments 53
10.5.3 Organophosphate Plunge
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Dips 53
10.6 Conclusion 54
References 54
11.1 Introduction 71
11.2 Griseofulvin 72
11.3 Amphotericin B and Other Polyenes 74
11.4 The Azoles 76
11.4.1 Steroidogenesis Inhibition 76
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11.4.2 Hepatotoxicity 79
11.4.3 Other Effects 79
11.5 Conclusions 80
References 81
12.1 Introduction 95
12.2 Individual Drugs or Groups of Drugs 95
12.2.1 The Benzimidazoles 95
12.2.2 Levamisole 98
12.2.3 Salicylanilides 99
12.2.4 Clorsulon 101
12.2.5 Tetrahydropyrimidines 102
12.2.6 Pyrazinoisoquinolones 104
12.2.7 Monepantel 107
12.2.8 Piperazine 108
12.2.9 Diethylcarbamazine 110
12.2.10 Nitroxynil 111
12.2.11 Halofuginone 112
12.2.12 Nitroimidazoles 113
12.2.13 Imidocarb 116
12.2.14 The Trypanocidal Drugs – Isometamidium
and Diminazene 118
12.2.15 Emodepside 122
12.3 Conclusions 123
References 126
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Contents xiii
Chapter 13 Some Other Pharmacologically Active Drugs 155
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CHAPTER 1
1.1 Introduction
Many people use, and are therefore potentially exposed to, veterinary medicinal
products. These include the pet-owning public, farmers, animal breeders and
keepers, and, of course, veterinarians and other veterinary staff such as veter-
inary nurses and practice receptionists. The public may be intermittently
exposed to veterinary medicinal products, apart from those with animals with
chronic conditions such as epilepsy and diabetes where exposures may be more
frequent. Farmers may be responsible for the administration of a wide variety
of drugs and, occasionally, exposures have the potential to be significant, for
example when dipping sheep and mixing or administering in-feed antimicrobial
agents. Veterinarians and veterinary nurses are potentially exposed to a wide
range of veterinary drugs including anaesthetics, euthanasia agents, anti-
neoplastic agents and non-steroidal anti-inflammatory drugs. It is thus
tempting to assume that these professionals are assailed on a daily basis by the
combined actions of a number of pharmacologically and toxicologically active
agents, and if these could be removed from veterinary practice, the world, or at
least the veterinary world, would be a better place in which to live and work.
However, just as it would be wrong to assume that the industrial workplace
is a chemophobe’s nightmare, or a toxicologists dream, it is equally incorrect to
think of the veterinary surgery or clinic as a toxicological playground.
Although industry, especially the chemical industry, has had its fair share of
chemical disasters, such as those involving asbestos, benzene, vinyl chloride
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2 Chapter 1
monomer and a number of halogenated hydrocarbons to name but a few, the
vast majority of mortalities and morbidities in industry arise from accidents
including those involving machinery, explosions and fires. Similarly, it would
be incorrect to assume that veterinary workers are immersed in toxic soups of
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pharmacologically active materials. Even if they were, there are numerous other
hazards, with associated risks, which may pose greater dangers than the
majority of pharmaceutical or biological agents encountered in veterinary
practice.
The main topic of this book is the potential for veterinary pharmaceutical
products to cause harm to human beings, especially through toxicological
modes of action. However, just as with industry, this must be seen in per-
spective with all other potential hazards and this chapter attempts to review this
perspective.
4 Chapter 1
products, mainly vaccines, and chemotherapeutants, including antimicrobial
drugs and antiparasitic agents, have been developed to combat or treat the
various conditions and to ensure the viability of the industry. The diseases are
diagnosed by veterinarians and others involved in animal health and welfare,
Published on 31 December 2012 on http://pubs.rsc.org | doi:10.1039/9781849735483-00001
and, similarly, the drugs and vaccines are administered by fish farm employees,
usually under the direction of a veterinarian. Hence, the environments where
fish farms are frequently located, or more specifically the environments where
salmon (and other cold water fish) are located, offer particular challenges in
terms of occupational safety.
Musculoskeletal disorders are common from lifting nets within cages where
the fish are reared and the feedstuffs used in aquaculture may attract rats, which
create a risk for leptospirosis. Other hazards include exposure to hydrogen
sulfide that arises from anaerobic reactions in the bottom of fishponds,
drowning, hypothermia, electricity, sunburn, fire and explosions from oxygen
exposure and ice-related accidents.27–29
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a
90% of human reactions involving vaccines or other injectable products were needlestick injuries.
b
91% of human reactions involving vaccines or other injectable products were needlestick injuries.
c
84% of human reactions involving vaccines or other injectable products were needlestick injuries.
d
88% of human reactions involving vaccines or other injectable products were needlestick injuries.
e
86% of human reactions involving vaccines or other injectable products were needlestick injuries.
1.2.4 Dermatoses
Non-infectious dermatoses are common among veterinarians. For example,
among a survey of veterinarians in Kansas, some 60% responded and, of these,
24 reported non-infectious recurrent or persistent dermatoses of the forearm, of
which 66% were related to work.126 In a European study, dermatologists were
questioned about their experiences with dermatoses in veterinarians. Seven
dermatologists had experiences with dermatoses in a total of 58 veterinarians