Veterinary Medicine Commons^™

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 …

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 …

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.

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 …

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 …

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 …

Medical Training Using Simulation: Toward Fewer Animals And Safer Patients, Jonathan Balcombe

Jonathan Balcombe, PhD

This paper presents the current status of computer-based simulation in medicine. Recent technological advances have enabled this field to emerge from esoteric explorations in academic laboratories to commercially available simulators designed to train users to perform medical procedures from start to finish. Today, more than a dozen companies are producing virtual reality simulators and interactive manikins for training in endoscopy, laparoscopy, anaesthesia, trauma management, angiography, and needle insertion. For many of these procedures, thousands of animals are still being used in training. Yet simulation has many advantages that can transcend scientific, ethical, economic and logistical problems that arise when using …