Research Methods in Life 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 …

An Evaluation Of The Us High Production Volume (Hpv) Chemical-Testing Programme: A Study In (Ir)Relevance, Redundancy And Retro Thinking, Andrew Nicholson, Jessica Sandler, Troy Seidle

Troy Seidle, PhD

Under the US Environmental Protection Agency (EPA) High Production Volume (HPV) Challenge Programme, chemical companies have volunteered to conduct screening-level toxicity tests on approximately 2800 widely-used industrial chemicals. Participating companies are committed to providing available toxicity information to the EPA and presenting testing proposals for review by the EPA and posting on the EPA Web site as public information. People for the Ethical Treatment of Animals (PETA) and a coalition of animal protection organisations have reviewed all the test plans submitted by the participating chemical companies for compliance with the original HPV framework, as well as with animal welfare guidelines …

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 …

Report Of The Working Group On Animal Distress In The Laboratory, Marilyn Brown, Larry Carbone, Kathleen Conlee, Marian Dawkins, Ian J. Duncan, David Fraser, Gilly Griffin, Victoria A. Hampshire, Lesley A. Lambert, Joy A. Mench, David Morton, Jon Richmond, Bernard E. Rollin, Andrew N. Rowan, Martin L. Stephens, Hanno Würbel

Andrew N. Rowan, DPhil

Finding ways to minimize pain and distress in research animals is a continuing goal in the laboratory animal research field. Pain and distress, however, are not synonymous, and often measures that alleviate one do not affect the other. Here, the authors provide a summary of a meeting held in February 2004 that focused on distress in laboratory animals. They discuss the difficulties associated with defining ‘distress,’ propose methods to aid in recognizing and alleviating distressful conditions, and provide recommendations for animal research conduct and oversight that would minimize distress experienced by laboratory animals.

The Ethics Of Animal Research: A Survey Of Pediatric Health Care Workers, Ari Joffe, Meredith Bara, Natalie Anton, Nathan Nobis

Experimentation Collection

Introduction: Pediatric health care workers (HCW) often perform, promote, and advocate use of public funds for animal research (AR). We aim to determine whether HCW consider common arguments (and counterarguments) in support (or not) of AR convincing.

Design: After development and validation, an e-mail survey was sent to all pediatricians and pediatric intensive care unit nurses and respiratory therapists (RTs) affiliated with a Canadian University. We presented questions about demographics, support for AR, and common arguments (with their counterarguments) to justify the moral permissibility (or not) of AR. Responses are reported using standard tabulations. Responses of pediatricians and nurses/RTs were …

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 …

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.

Monkey-Based Research On Human Disease: The Implications Of Genetic Differences, Jarrod Bailey

Laboratory Experiments Collection

Assertions that the use of monkeys to investigate human diseases is valid scientifically are frequently based on a reported 90–93% genetic similarity between the species. Critical analyses of the relevance of monkey studies to human biology, however, indicate that this genetic similarity does not result in sufficient physiological similarity for monkeys to constitute good models for research, and that monkey data do not translate well to progress in clinical practice for humans. Salient examples include the failure of new drugs in clinical trials, the highly different infectivity and pathology of SIV/HIV, and poor extrapolation of research on Alzheimer’s disease, Parkinson’s …

Arkansas Animal Science Department Report 2014, David L. Kreider, Paul Beck

Arkansas Agricultural Experiment Station Research Series

No abstract provided.

Annotated Bibliography: Attitudes Toward Animal Research (1998-2013), Erich Yahner

BIBLIOGRAPHIES

No abstract provided.

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 …

Sma-Causing Missense Mutations In Survival Motor Neuron (Smn) Display A Wide Range Of Phenotypes When Modeled In Drosophila, Kavita Praveen, Ying Wen, Kelsey M. Gray, John J. Noto, Akash R. Patlolla, Gregory D. Van Duyne, A. Gregory Matera

Biology, Chemistry, and Environmental Sciences Faculty Articles and Research

Mutations in the human survival motor neuron 1 (SMN) gene are the primary cause of spinal muscular atrophy (SMA), a devastating neuromuscular disorder. SMN protein has a well-characterized role in the biogenesis of small nuclear ribonucleoproteins (snRNPs), core components of the spliceosome. Additional tissue-specific and global functions have been ascribed to SMN; however, their relevance to SMA pathology is poorly understood and controversial. Using Drosophila as a model system, we created an allelic series of twelve Smn missense mutations, originally identified in human SMA patients. We show that animals expressing these SMA-causing mutations display a broad range of …

Effects Of Pde4 Pathway Inhibition In Rat Experimental Stroke, Fan Yang, Rachita K. Sumbria, Dong Xue, Chuanhui Yu, Dan He, Shuo Liu, Annlia Paganini-Hill, Mark J. Fisher

Pharmacy Faculty Articles and Research

PURPOSE: The first genomewide association study indicated that variations in the phosphodiesterase 4D (PDE4D) gene confer risk for ischemic stroke. However, inconsistencies among the studies designed to replicate the findings indicated the need for further investigation to elucidate the role of the PDE4 pathway in stroke pathogenesis. Hence, we studied the effect of global inhibition of the PDE4 pathway in two rat experimental stroke models, using the PDE4 inhibitor rolipram. Further, the specific role of the PDE4D isoform in ischemic stroke pathogenesis was studied using PDE4D knockout rats in experimental stroke. METHODS: Rats were subjected to either the …

Public Attitudes Toward Animal Research: A Review, Elisabeth H. Ormandy, Catherine A. Schuppli

Attitudes Toward Animal Research Collection

The exploration of public attitudes toward animal research is important given recent developments in animal research (e.g., increasing creation and use of genetically modified animals, and plans for progress in areas such as personalized medicine), and the shifting relationship between science and society (i.e., a move toward the democratization of science). As such, public engagement on issues related to animal research, including exploration of public attitudes, provides a means of achieving socially acceptable scientific practice and oversight through an understanding of societal values and concerns. Numerous studies have been conducted to explore public attitudes toward animal use, and more specifically …

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

A Review Of The Institute Of Medicine’S Analysis Of Using Chimpanzees In Biomedical Research, Robert C. Jones, Ray Greek

Biomedicine and Animal Models in Research Collection

We argue that the recommendations made by the Institute of Medicine’s 2011 report, Chimpanzees in Biomedical and Behavioral Research: Assessing the Necessity, are methodologically and ethically confused. We argue that a proper understanding of evolution and complexity theory in terms of the science and ethics of using chimpanzees in biomedical research would have had led the committee to recommend not merely limiting but eliminating the use of chimpanzees in biomedical research. Specifically, we argue that a proper understanding of the difference between the gross level of examination of species and examinations on finer levels can shed light on important methodological …

An Analysis Of The Use Of Animal Models In Predicting Human Toxicology And Drug Safety, Jarrod Bailey, Michelle Thew, Michael Balls

Experimentation Collection

Animal use continues to be central to preclinical drug development, in spite of a lack of its demonstrable validity. The current nadir of new drug approvals and the drying-up of pipelines may be a direct consequence of this. To estimate the evidential weight given by animal data to the probability that a new drug may be toxic to humans, we have calculated Likelihood Ratios (LRs) for an extensive data set of 2,366 drugs, for which both animal and human data are available, including tissue-level effects and MedDRA Level 1–4 biomedical observations. This was done for three preclinical species (rat, mouse …

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.

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 …

A Longitudinal View Of Primate Life In Two American Laboratories, Jonathan Balcombe

Experimentation Collection

If representative of other facilities, our findings uncover serious welfare concerns for the wellbeing of primates kept in American research facilities. These animals face regular or chronic sources of pain and distress including noxious experimental and non‐experimental events and illness and injury; and severe and prolonged social disruptions. Pain relief is meager by comparison to that normally provided to humans, despite legislative requirements to minimize pain and distress and assume similarity to humans in terms of ability to experience pain and distress. Living environments are usually confinement indoors to a metal cage, often alone, and often with a minimum of …

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 …

A Multivariate Model Of Stakeholder Preference For Lethal Cat Management, Dara M. Wald, Susan K. Jacobson

Dara Wald

Moving Beyond The Welfare Standard Of Psychological Well-Being For Nonhuman Primates: The Case Of Chimpanzees, John P. Gluck

Experimentation Collection

Since 1985, the US Animal Welfare Act and Public Health Service policy have required that researchers using nonhuman primates in biomedical and behavioral research develop a plan ‘‘for a physical environment adequate to promote the psychological well-being of primates.’’ In pursuing this charge, housing attributes such as social companionship, opportunities to express species-typical behavior, suitable space for expanded locomotor activity, and nonstressful relationships with laboratory personnel are dimensions that have dominated the discussion. Regulators were careful not to direct a specific set of prescriptions (i.e., engineering standards) for the attainment of these goals, but to leave the design of the …

Rethinking The Ethics Of Research Involving Nonhuman Animals: Introduction, Tom L. Beauchamp, Hope Ferdowsian, John P. Gluck

Experimentation Collection

No abstract provided.

Paracrine-Rescued Lobulogenesis In Chimeric Outgrowths Comprising Progesterone-Receptor-Null Mammary Epithelium And Redirected Wild-Type Testicular Cells, Robert D. Bruno, Corinne A. Boulanger, Sonia M. Rosenfield, Lisa H. Anderson, John P. Lydon, Gilbert H. Smith

Medical Diagnostics & Translational Sciences Faculty Publications

We have previously shown that non-mammary and tumorigenic cells can respond to the signals of the mammary niche and alter their cell fate to that of mammary epithelial progenitor cells. Here we tested the hypothesis that paracrine signals from mammary epithelial cells expressing progesterone receptor (PR) are dispensable for redirection of testicular cells, and that re-directed wild-type testicular-derived mammary cells can rescue lobulogenesis of PR-null mammary epithelium by paracrine signaling during pregnancy. We injected PR-null epithelial cells mixed with testicular cells from wild-type adult male mice into cleared fat-pads of recipient mice. The testicular cells were redirected in vivo to …

The Usefulness Of Systematic Reviews Of Animal Experiments For The Design Of Preclinical And Clinical Studies, Rob B.M. De Vries, Kimberley E. Weaver, Marc T. Avey, Martin Stephens, Emily S. Sena, Marlies Leenaars

Experimentation Collection

The question of how animal studies should be designed, conducted, and analyzed remains underexposed in societal debates on animal experimentation. This is not only a scientific but also amoral question. After all, if animal experiments are not appropriately designed, conducted, and analyzed, the results produced are unlikely to be reliable and the animals have in effect been wasted. In this article, we focus on one particular method to address this moral question, namely systematic reviews of previously performed animal experiments. We discuss how the design, conduct, and analysis of future (animal and human) experiments may be optimized through such systematic …