Veterinary Medicine Commons^™

Examining The Regulatory Value Of Multi-Route Mammalian Acute Systemic Toxicity Studies, Troy Seidle, Pilar Prieto, Anna Bulgheroni

Troy Seidle, PhD

Regulatory information requirements for pesticides call for submission of acute systemic toxicity data for up to three different exposure routes (oral, dermal, inhalation) for both active ingredients and formulated products. Similar multi-route testing is required in the European Union and elsewhere for industrial chemicals. To determine the value of acute toxicity testing by more than one route, oral-dermal and oralinhalation concordances among regulatory classifications were examined for large data sets of chemicals and pesticide active ingredients. Across all sectors examined, oral acute toxicity classifications for pure active substances were more severe than those derived from dermal data in more than …

A Modular One-Generation Reproduction Study As A Flexible Testing System For Regulatory Safety Assessment, Richard Vogel, Troy Seidle, Horst Spielmann

Troy Seidle, PhD

The European Union’s Registration, Evaluation and Authorisation of Chemicals (REACH) legislation mandates testing and evaluation of approximately 30,000 existing substances within a short period of time, beginning with the most widely used “high production volume” (HPV) chemicals. REACH testing requirements for the roughly 3000 HPV chemicals specify three separate tests for reproductive toxicity: two developmental toxicity studies on different animal species (OECD Test Guideline 414) and a two-generation reproduction toxicity study (OECD TG 416). These studies are highly costly in both economic and animal welfare terms. OECD TG 416 is a fertility study intended to evaluate reproductive performance of animals …

Humane Society International’S Global Campaign To End Animal Testing, Troy Seidle

Troy Seidle, PhD

The Research & Toxicology Department of Humane Society International (HSI) operates a multifaceted and science-driven global programme aimed at ending the use of animals in toxicity testing and research. The key strategic objectives include: a) ending cosmetics animal testing worldwide, via the multinational Be Cruelty-Free campaign; b) achieving near-term reductions in animal testing requirements through revision of product sector regulations; and c) advancing humane science by exposing failing animal models of human disease and shifting science funding toward human biology-based research and testing tools fit for the 21st century. HSI was instrumental in ensuring the implementation of the March 2013 …

The Three Rs: The Way Forward, Michael Balls, Alan M. Goldberg, Julia H. Fentem, Caren L. Broadhead, Rex L. Burch, Michael F.W. Festing, John M. Frazier, Coenraad F.M. Hendriksen, Margaret Jennings, Margot D.O. Van Der Kamp, David B. Morton, Andrew N. Rowan, Claire Russell, William M.S. Russell, Horst Spielmann, Martin Stephens, William S. Stokes, Donald W. Straughan, James D. Yager, Joanne Zurlo, Bert F.M. Van Zutphen

Andrew N. Rowan, DPhil

This is the report of the eleventh of a series of workshops organised by the European Centre for the Validation of Alternative Methods (ECVAM), which was established in 1991 by the European Commission. ECVAM's main goal, as defined in 1993 by its Scientific Advisory Committee, is to promote the scientific and regulatory acceptance of alternative methods which are of importance to the biosciences and which reduce, refine or replace the use of laboratory animals. One of the first priorities set by ECVAM was the implementation of procedures which would enable it to become well-informed about the state-of-the-art of non-animal test …

Biomarkers Of Inflammation, Metabolism, And Oxidative Stress In Blood, Liver, And Milk Reveal A Better Immunometabolic Status In Peripartal Cows Supplemented With Smartamine M Or Metasmart, J. S. Osorio, E. Trevisi, P. Ji, J. K. Drackley, D. Luchini, G. Bertoni, J. J. Loor

Physiology Collection

The peripartal dairy cow experiences a state of reduced liver function coupled with increased inflammation and oxidative stress. This study evaluated the effect of supplementing basal diets with rumen-protected Met in the form of MetaSmart (MS) or Smartamine M (SM) (both from Adisseo Inc., Antony, France) during the peripartal period on blood and hepatic biomarkers of liver function, inflammation, and oxidative stress. Thirty-seven multiparous Holstein cows were fed the same basal diet from −50 to −21 d relative to expected calving [1.24 Mcal/kg of dry matter (DM); no Met supplementation]. From −21 d to calving, the cows received diets …

Carbon Dioxide For Euthanasia: Concerns Regarding Pain And Distress, With Special Reference To Mice And Rats, Kathleen Conlee, Martin Stephens, Andrew N. Rowan, Lesley A. King

Andrew N. Rowan, DPhil

Carbon dioxide (CO₂) is the most commonly used agent for euthanasia of laboratory rodents, used on an estimated tens of millions of laboratory rodents per year worldwide, yet there is a growing body of evidence indicating that exposure to CO₂ causes more than momentary pain and distress in these and other animals. We reviewed the available literature on the use of CO₂ for euthanasia (as well as anaesthesia) and also informally canvassed laboratory animal personnel for their opinions regarding this topic. Our review addresses key issues such as CO₂ flow rate and final concentration, presence …

A Vision Becoming Reality, Gill Langley

Gill Langley, PhD

Non-animal science in toxicology and health research has been progressing for decades, but only now is it being seen widely as advanced science. The emergence of novel human biology-based tools and models, combined with legislative and regulatory change, a 21st century concept for toxicology, continuing failures in the drug pipeline, and systematic critiques of animal models, have created a pivotal moment of change. The leading edge is starting to become the norm. Humans and other animals are likely to benefit as a result.

Estimates For Worldwide Laboratory Animal Use In 2005, Katy Taylor, Nicky Gordon, Gill Langley, Wendy Higgins

Gill Langley, PhD

Animal experimentation continues to generate public and political concern worldwide. Relatively few countries collate and publish animal use statistics, yet this is a first and essential step toward public accountability and an informed debate, as well as being important for effective policy-making and regulation. The implementation of the Three Rs (replacement, reduction and refinement of animal experiments) should be expected to result in a decline in animal use, but without regular, accurate statistics, this cannot be monitored. Recent estimates of worldwide annual laboratory animal use are imprecise and unsubstantiated, ranging from 28–100 million. We collated data for 37 countries that …

Volunteer Studies In Pain Research — Opportunities And Challenges To Replace Animal Experiments: The Report And Recommendations Of A Focus On Alternatives Workshop, C. K. Langley, Q. Aziz, C. Bountra, N. Gordon, P. Hawkins, A. Jones, G. Langley, T. Nurmikko, I. Tracey

Gill Langley, PhD

Despite considerable research, effective and safe treatments for human pain disorders remain elusive. Understanding the biology of different human pain conditions and researching effective treatments continue to be dominated by animal models, some of which are of limited value. British and European legislation demands that non-animal approaches should be considered before embarking on research using experimental animals. Recent scientific and technical developments, particularly in human neuroimaging, offer the potential to replace some animal procedures in the study of human pain. A group of pain research experts from academia and industry met with the aim of exploring creatively the tools, strategies …

Considering A New Paradigm For Alzheimer’S Disease Research, Gillian R. Langley

Gill Langley, PhD

Using Alzheimer’s disease as a case study, this review argues that it might be time to consider a new paradigm in medical research and drug discovery. The existing framework is overly dependent on often unvalidated animal models, particularly transgenic mice. Translational success remains elusive and costly late-stage drug failure is common. The conventional paradigm tends to overlook species differences and assumes that animal-based findings are generally applicable to humans. Could pathways-based research using advanced human-specific models probed with new tools, including those of systems biology, take centre stage? The current transition in chemical toxicology to a 21st-century paradigm could be …

The Validity Of Animal Experiments In Medical Research, Gill Langley

Gill Langley, PhD

Other animals, such as mice, rats, rabbits, dogs and monkeys, are widely used as surrogates for humans in fundamental medical research. This involves creating disorders in animals by chemical, surgical or genetic means, with the aim of mimicking selected aspects of human illnesses. It is a truism that any model or surrogate is not identical to the target being modelled. So, in medical research, experiments using animals or cell cultures or even healthy volunteers instead of patients (being the target population with the target illness) will inevitably have limitations, although these will be greater or lesser depending on the model.

Evaluation Of Awarded Grant Applications Involving Animal Experimentation, Michael W. Fox, M. Andrea Ward, Andrew N. Rowan, Barbara Jaffe

Andrew N. Rowan, DPhil

The potential benefits of animal research are accepted by most. However, painstaking care must be applied to the approach and design of the research to ensure the best possible chance of achieving the research objectives and to minimize both physical and psychological distress to the animals. Consideration should be given not only to transport and housing conditions, but also to practices used in the laboratory. Adequate reasons must also be given as to why the research is necessary.

Public concern over the use and care of laboratory animals in biomedical programs contributed to the passage of the Animal Welfare Act …

Evaluation Of Awarded Grant Applications Involving Animal Experimentation, Michael W. Fox, M. Andrea Ward, Andrew N. Rowan

Andrew N. Rowan, D.Phil.

The potential benefits of animal research are accepted by most. However, painstaking care must be applied to the approach and design of the research to ensure the best possible chance of achieving the research objectives and to minimize both physical and psychological distress to the animals. Consideration should be given not only to transport and housing conditions, but also to practices used in the laboratory. Adequate reasons must also be given as to why the research is necessary. Public concern over the use and care of laboratory animals in biomedical programs contributed to the passage of the Animal Welfare Act …

Acceptance Of Simulated Oral Rabies Vaccine Baits By Urban Raccoons, John Hadidian, Suzanne R. Jenkins, David H. Johnston, Peter J. Savarie, Victor F. Nettles, David M. Manski, George M. Baer

John Hadidian, PhD

In summer 1986, a study was conducted to evaluate raccoon (Procyon lotor) acceptance of oral baits that could be used for rabies vaccination, One thousand wax-coated sponge bait cubes were filled with 5 mg of a seromarker (iophenoxic acid), placed in polyethylene bags, and hand-distributed in an 80 ha area within an urban National Park in Washington, D.C. (USA), After 3 wk, target and nontarget animals were trapped and blood samples collected to evaluate bait uptake. Thirty-three of 52 (63%) raccoons had elevated blood iodine levels indicating they had eaten at least one bait, 13 (25%) were negative, and six …

Long-Term Health Effects Of Neutering Dogs: Comparison Of Labrador Retrievers With Golden Retrievers, Benjamin L. Hart, Lynette A. Hart, Abigail P. Thigpen, Neil H. Willits

Endocrinology Collection

Our recent study on the effects of neutering (including spaying) in Golden Retrievers in markedly increasing the incidence of two joint disorders and three cancers prompted this study and a comparison of Golden and Labrador Retrievers. Veterinary hospital records were examined over a 13-year period for the effects of neutering during specified age ranges: before 6 mo., and during 6–11 mo., year 1 or years 2 through 8. The joint disorders examined were hip dysplasia, cranial cruciate ligament tear and elbow dysplasia. The cancers examined were lymphosarcoma, hemangiosarcoma, mast cell tumor, and mammary cancer. The results for the Golden Retriever …

Physiological And Behavioural Responses To Noxious Stimuli In The Atlantic Cod (Gadus Morhua), Jared R. Eckroth, Øyvind Aas-Hansen, Lynne U. Sneddon, Helena Bichão, Kjell B. Døving

Aquaculture Collection

In the present study, our aim was to compare physiological and behavioural responses to different noxious stimuli to those of a standardized innocuous stimulus, to possibly identify aversive responses indicative of injury detection in a commercially important marine teleost fish, the Atlantic cod. Individual fish were administered with a noxious stimulus to the lip under short-term general anaesthesia (MS-222). The noxious treatments included injection of 0.1% or 2% acetic acid, 0.005% or 0.1% capsaicin, or piercing the lip with a commercial fishing hook. Counts of opercular beat rate (OBR) at 10, 30, 60, 90 and 120 min and observations of …

Scientists And Animal Research: Dr. Jekyll Or Mr. Hyde?, Andrew N. Rowan

Andrew N. Rowan, DPhil

Why is the public so sensitive about the use of a few tens of millions of animals in research when they do not object to killing hundreds of millions of pigs and cows and billions of chickens for our meat diet? Why is animal research considered so bad despite the public's high opinion of science (and scientists)? Perhaps it is the image of the scientist as an objective and cold individual who deliberately inflicts harm (pain, distress, or death) on his (the public image is usually male) innocent animal victims that arouses so much horror and concern. This paper does …

Prolonged Pain Research In Mice: Trends In Reference To The 3rs, Jonathan Balcombe, Hope Ferdowsian, Lauren Briese

Jonathan Balcombe, PhD

This literature review documents trends in the use of mice in prolonged pain research, defined herein as research that subjects mice to a source of pain for at least 14 days. The total amount of prolonged pain research on mice has increased dramatically in the past decade for the 3 pain categories examined: neuropathic, inflammatory, and chronic pain. There has also been a significant rise in the number of prolonged mouse pain studies as a proportion of all mouse studies and of all mouse pain studies. The use of transgenic mice has also risen significantly in prolonged pain research, though …

Cancerous Contradictions: The Mis-Regulation Of Human Carcinogens Based On Animal Data, Andrew Knight, Jarrod Bailey, Jonathan Balcombe

Jonathan Balcombe, PhD

The regulation of human exposures to potential carcinogens constitutes society’s most important use of animal carcinogenicity data. However, for environmental contaminants of greatest U.S. concern, we found that in most cases (58.1%; 93/160) the U.S. Environmental Protection Agency (EPA) considered the animal data inadequate to support a classification of probable human carcinogen or noncarcinogen.

The World Health Organisation’s International Agency for Research on Cancer (IARC) is a leading international authority on carcinogenicity assessments. For chemicals lacking human exposure data (the great majority), IARC classifications of identical chemicals were significantly more conservative than EPA classifications (p

The 24th Annual Research Conference Abstract Booklet, Nikki Lynn Rogers

University of Gondar Research Conferences

Staff members, postgraduate and senior undergraduate students of the University, invited guests and speakers participated in the conference. The annual conference of the University is meant to share experiences in research activities among juniors and seniors, staff and students, and invited guests. It is also meant to motivate students and young faculty to engage in research and also to initiate and strengthen interdisciplinary collaborations. The findings of the studies and the resulting recommendations are expected to be used in solving the diverse societal problems we have been facing.

Research activities at the University of Gondar are primarily aimed at solving …

Laboratory Rodent Welfare: Thinking Outside The Cage, Jonathan P. Balcombe

Jonathan Balcombe, PhD

This commentary presents the case against housing rats and mice in laboratory cages; the commentary bases its case on their sentience, natural history, and the varied detriments of laboratory conditions. The commentary gives 5 arguments to support this position: (a) rats and mice have a high degree of sentience and can suffer, (b) laboratory environments cause suffering, (c) rats and mice in the wild have discrete behavioral needs, (d) rats and mice bred for many generations in the laboratory retain these needs, and (e) these needs are not met in laboratory cages.

T-61 Use In The Euthanasia Of Domestic Animals: A Survey, Andrew N. Rowan

Andrew N. Rowan, DPhil

A variety of techniques have been proposed and employed for the killing of domestic animals but relatively few have survived as suitable agents for euthanasia-namely, the induction of painless, suffering-free death. Some agents, such as strychnine, curariform agents, or potassium salts cause suffering while others have other disadvantages. 'lbday, dogs and cats are commonly euthanatized with sodium pentobarbital or with T-61 which is a mixture of a central nervous system narcotic, a paralytic agent, and a local anesthetic. The use of T-61 was first reported in the United States in 1963 (Quin 1963). The substance gradually became more popular because …

The Human/Animal Interface: Emergence And Resurgence Of Zoonotic Infectious Diseases, Michael Greger

Michael Greger, MD, FACLM

Emerging infectious diseases, most of which are considered zoonotic in origin, continue to exact a significant toll on society. The origins of major human infectious diseases are reviewed and the factors underlying disease emergence explored. Anthropogenic changes, largely in land use and agriculture, are implicated in the apparent increased frequency of emergence and reemergence of zoonoses in recent decades. Special emphasis is placed on the pathogen with likely the greatest zoonotic potential, influenzavirus A.

Amyloid Fibrils: Potential Food Safety Implications, Michael Greger

Michael Greger, MD, FACLM

The demonstration of oral Amyloid-A (AA) fibril transmissibility has raised food safety questions about the consumption of amyloidotic viscera. In a presumed prion-like mechanism, amyloid fibrils have been shown to trigger and accelerate the development of AA amyloidosis in rodent models. The finding of amyloid fibrils in edible avian and mammalian food animal tissues, combined with the inability of cooking temperatures to eliminate their amyloidogenic potential, has led to concerns that products such as pâté de foie gras may activate a reactive systemic amyloidosis in susceptible consumers. Given the ability of amyloid fibrils to cross-seed the formation of chemically heterologous …

Laboratory Routines Cause Animal Stress, Jonathan P. Balcombe, Neal D. Barnard, Chad Sandusky

Jonathan Balcombe, PhD

Eighty published studies were appraised to document the potential stress associated with three routine laboratory procedures commonly performed on animals: handling, blood collection, and orogastric gavage. We defined handling as any non-invasive manipulation occurring as part of routine husbandry, including lifting an animal and cleaning or moving an animal's cage. Significant changes in physiologic parameters correlated with stress (e.g., serum or plasma concentrations of corticosterone, glucose, growth hormone or prolactin, heart rate, blood pressure, and behavior) were associated with all three procedures in multiple species in the studies we examined. The results of these studies demonstrated that animals responded with …

Their Bugs Are Worse Than Their Bite: Emerging Infectious Disease And The Human-Animal Interface, Michael Greger

Michael Greger, MD, FACLM

In the twenty-five years since that announcement, what we now know as AIDS has killed 20 million people (National AIDS Trust 2005). Where did the AIDS virus— and other emerging diseases, such as severe acute respiratory syndrome (SARS), Ebola, mad cow— come from?

The Long Haul: Risks Associated With Livestock Transport, Michael Greger

Michael Greger, MD, FACLM

The Food and Agriculture Organization (FAO) of the United Nations describes live animal transport as “ideally suited for spreading disease,” given that animals may originate from different herds or flocks and are “confined together for long periods in a poorly ventilated stressful environment.” Given the associated “serious animal and public health problems,” the Federation of Veterinarians of Europe has called for the replacement of the long-distance transportation of live animals for slaughter as much as possible to a “carcass-only trade.” In the United States, more than 50 million live cattle, sheep, and pigs and an unknown number of the more …

An Hsi Fact Sheet: Avian Influenza In India, Humane Society International

HSI FACT SHEETS

Avian influenza (AI), commonly known as bird flu, typically causes little or no harm to its wild waterfowl hosts. In 2003-2004, however, nine Asian countries reported unprecedented outbreaks of high-mortality AI in domestic poultry. This viral lineage, subtype H5N1, has spread to over 60 countries, and is considered endemic in at least four.

In India, H5N1 outbreaks were first recorded in 2006, and have continued each year since, reaching a total of 86 by 2012. Millions of India’s chickens and ducks have been culled in efforts to contain and eliminate the virus. India has declared itself free of AI a …

Animal Carcinogenicity Studies: Implications For The Reach System, Andrew Knight, Jarrod Bailey, Jonathan Balcombe

Jonathan Balcombe, PhD

The 2001 European Commission proposal for the Registration, Evaluation and Authorisation of Chemicals (REACH) aims to improve public and environmental health by assessing the toxicity of, and restricting exposure to, potentially toxic chemicals. The greatest benefits are expected to accrue from decreased cancer incidences. Hence the accurate identification of chemical carcinogens must be a top priority for the REACH system. Due to a paucity of human clinical data, the identification of potential human carcinogens has conventionally relied on animal tests. However, our survey of the US Environmental Protection Agency’s (EPA’s) toxic chemicals database revealed that, for a majority of the …

Animal Carcinogenicity Studies: 1. Poor Human Predictivity, Andrew Knight, Jarrod Bailey, Jonathan Balcombe

Jonathan Balcombe, PhD

The regulation of human exposure to potentially carcinogenic chemicals constitutes society’s most important use of animal carcinogenicity data. Environmental contaminants of greatest concern within the USA are listed in the Environmental Protection Agency’s (EPA’s) Integrated Risk Information System (IRIS) chemicals database. However, of the 160 IRIS chemicals lacking even limited human exposure data but possessing animal data that had received a human carcinogenicity assessment by 1 January 2004, we found that in most cases (58.1%; 93/160), the EPA considered animal carcinogenicity data inadequate to support a classification of probable human carcinogen or non-carcinogen. For the 128 chemicals with human or …