Medicine and Health Sciences 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 …

The Development Of New Concepts For Assessing Reproductive Toxicity Applicable To Large Scale Toxicological Programmes, S. Bremer, C. Pellizzer, S. Hoffmann, T. Seidle, T. Hartung

Troy Seidle, PhD

Large scale toxicological testing programmes which are currently ongoing such as the new European chemical legislation REACH require the development of new integrated testing strategies rather than applying traditional testing schemes to thousands of chemicals. The current practice of requiring in vivo testing for every possible adverse effect endanger the success of these programmes due (i) to limited testing facilities and sufficient capacity of scientific/technical knowledge for reproductive toxicity; (ii) an unacceptable number of laboratory animals involved (iii) an intolerable number of chemicals classified as false positive.

A key aspect of the implementation of new testing strategies is the determination …

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 …

Ideology Masquerading As Science: The Case Of Endocrine Disrupter Screening Programmes, Troy Seidle

Troy Seidle, PhD

The global move to develop novel testing methods and strategies to identify suspected endocrine disrupting chemicals offers a unique opportunity to move away from traditional animal testing paradigms in this new area of regulatory concern. Regrettably, the programmes under development, both in the USA and internationally through the OECD, have thus far failed to consider in vitro and other nonanimal test methods as more than “pre-screening” or “priority-setting” tools in a larger, animal-based testing strategy. Validation efforts to date have focused almost exclusively on the modification of existing animal tests to detect “endocrine effects”, with no demonstrable effort to promote …

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 …

Evaluation Of The Effect Of Orally Administered Acid Suppressants On Intragastric Ph In Cats, S Parkinson, M Katherine Tolbert, K Messenger, A. Odunayo, M. Brand, G. Davidson, E. Peters, A. Reed, M. G. Papich

M Katherine Tolbert DVM, PhD, DACVIM

Background Acid suppressant drugs are a mainstay of treatment for cats with gastrointestinal erosion and ulceration. However, clinical studies have not been performed to compare the efficacy of commonly PO administered acid suppressants in cats.

Hypothesis/Objectives To compare the effect of PO administered famotidine, fractionated omeprazole tablet (fOT), and omeprazole reformulated paste (ORP) on intragastric pH in cats. We hypothesized that both omeprazole formulations would be superior to famotidine and placebo.

Animals Six healthy adult DSH colony cats.

Methods Utilizing a randomized, 4-way crossover design, cats received 0.88–1.26 mg/kg PO q12h fOT, ORP, famotidine, and placebo (lactose capsules). Intragastric pH …

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 …

Possibilities For Refinement And Reduction: Future Improvements Within Regulatory Testing, Martin L. Stephens, Kathleen Conlee, Gina Alvino, Andrew N. Rowan

Andrew N. Rowan, DPhil

Approaches and challenges to refining and reducing animal use in regulatory testing are reviewed. Regulatory testing accounts for the majority of animals reported in the most painful and/or distressful categories in the United States and Canada. Refinements in testing, including the use of humane endpoints, are of increasing concern. Traditional approaches to reduction (e.g., improving experimental design) are being supplemented with complementary approaches, such as the use of tier testing to eliminate some chemicals prior to in vivo testing. Technological advances in telemetry and noninvasive techniques will help decrease either the demand for animals in testing or animal suffering. Further …

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.

Animal Models And Therapeutic Molecular Targets Of Cancer: Utility And Limitations., Maria Cekanova Ms, Rndr, Phd, Kusum Rathore

Maria Cekanova MS, RNDr, PhD

Cancer is the term used to describe over 100 diseases that share several common hallmarks. Despite prevention, early detection, and novel therapies, cancer is still the second leading cause of death in the USA. Successful bench-to-bedside translation of basic scientific findings about cancer into therapeutic interventions for patients depends on the selection of appropriate animal experimental models. Cancer research uses animal and human cancer cell lines in vitro to study biochemical pathways in these cancer cells. In this review, we summarize the important animal models of cancer with focus on their advantages and limitations. Mouse cancer models are well known, …

Infection And Immunity In The Pacific White Shrimp, Litopenaeus Vannamei, John Dustin Loy

John Loy

Infectious diseases are significant impediments to the growth and sustainability of commercial shrimp aquaculture. Endemic diseases such as that caused by the obligate intracellular parasite the Necrotizing Hepatopancreatitis Bacterium (NHPB), cause significant losses to shrimp producers thoughout the Americas. New and emerging viral diseases, such as that caused by Infectious myonecrosis virus (IMNV), have caused tremendous economic losses in farmed Pacific white shrimp (Litopenaeus vannamei), since it emerged in Brazil and subsequently spread across the globe to Indonesia. No methods exist to propagate and model these infections in vitro), as no cell culture lines are available for shrimp. Therefore, we …

Development And Evaluation Of A Replicon Particle Vaccine Expressing The E2 Glycoprotein Of Bovine Viral Diarrhea Virus (Bvdv) In Cattle, John Dustin Loy, Jill Gander, Mark Mogler, Ryan Vander Veen, Julia Ridpath, Delbert Hank Harris, Kurt Kamrud

John Loy

Background: Bovine viral diarrhea virus is one of the most significant and costly viral pathogens of cattle worldwide. Alphavirus-derived replicon particles have been shown to be safe and highly effective vaccine vectors against a variety of human and veterinary pathogens. Replicon particles are non-propagating, DIVA compatible, and can induce both humoral and cell mediated immune responses. This is the first experiment to demonstrate that Alphavirus-based replicon particles can be utilized in a standard prime/boost vaccination strategy in calves against a commercially significant bovine pathogen. Findings: Replicon particles that express bovine viral diarrhea virus sub-genotype 1b E2 glycoprotein were generated and …

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 …

Intraocular Pressure Changes In Equine Athletes During Endurance Competitions, Rachel A. Allbaugh, Susan M. Keil, Zhining Ou, Nora M. Bello

Rachel A. Allbaugh

Objective To assess intraocular pressure (IOP) in conditioned equine athletes and document changes with exercise. A secondary objective was to assess associations between IOP and heart rate, as well as with other subjective physical parameters.

Sample Population Horses were evaluated during 50 mile endurance ride competitions. Data were collected on 69 horses during 5 different competitions at 3 different locations with 59 horses ridden once, 9 horses ridden in two competitions, and 1 horse ridden in three competitions for a total of 80 horse-ride combinations.

Procedures Intraocular pressure was measured using a TonoVet® tonometer in both eyes of each horse …

Diseases Of The Pharynx, Charles W. Raker

Charles W. Raker (1920 - 2014)

No abstract provided.

Diseases Of The Guttural Pouch, Charles W. Raker

Charles W. Raker (1920 - 2014)

No abstract provided.

Clinical Observations Of Bone And Joint Diseases In Horses, Charles W. Raker

Charles W. Raker (1920 - 2014)

Bone and joint diseases in the horse, as observed by the veterinary clinician, assume many forms frequently producing signs of lameness. The bones or joints of the limbs are most commonly affected and many factors which operate either singly or collectively produce the lesions observed.

Congenital Lateral Luxation Of The Patella In The Horse, James R. Rooney, Charles W. Raker, K. J. Harmany

Charles W. Raker (1920 - 2014)

Lateral luxation of the patella has been described in horses and ponies. Medial luxation has been reported only twice. Upward fixation of the patella is not true luxation. This report concerns two cases of lateral luxation of the patella related to hypoplasia of the lateral ridge of the trochlea of the femur.

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 …

The Future Of Teratology Research Is In Vitro, Jarrod Bailey, Andrew Knight, Jonathan Balcombe

Jonathan Balcombe, Ph.D.

Birth defects induced by maternal exposure to exogenous agents during pregnancy are preventable, if the agents themselves can be identified and avoided. Billions of dollars and manhours have been dedicated to animal-based discovery and characterisation methods over decades. We show here, via a comprehensive systematic review and analysis of this data, that these methods constitute questionable science and pose a hazard to humans. Mean positive and negative predictivities barely exceed 50%; discordance among the species used is substantial; reliable extrapolation from animal data to humans is impossible, and virtually all known human teratogens have so far been identified in spite …

The Future Of Teratology Research Is In Vitro, Jarrod Bailey, Andrew Knight, Jonathan Balcombe

Jonathan Balcombe, PhD

Birth defects induced by maternal exposure to exogenous agents during pregnancy are preventable, if the agents themselves can be identified and avoided. Billions of dollars and manhours have been dedicated to animal-based discovery and characterisation methods over decades. We show here, via a comprehensive systematic review and analysis of this data, that these methods constitute questionable science and pose a hazard to humans. Mean positive and negative predictivities barely exceed 50%; discordance among the species used is substantial; reliable extrapolation from animal data to humans is impossible, and virtually all known human teratogens have so far been identified in spite …

Dissection: The Scientific Case For Alternatives, Jonathan Balcombe

Jonathan Balcombe, PhD

This article presents the scientific argument that learning methods that replace traditional nonhuman animal-consumptive methods in life science education—so-called alternatives to dissection—are pedagogically sound and probably superior to dissection. This article focuses on the pedagogy, a learning method’s effectiveness for conveying knowledge.

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 …