11

ALTERNATIVE TO ALTERNATIVE TO ANIMAL STUDYANIMAL STUDY

Presented by:- S.S.CPresented by:- S.S.CM.Pharm (1M.Pharm (1stst Sem.) Sem.)

Department of PharmacologyDepartment of PharmacologyR. C. Patel College of Pharmacy, Shirpur.R. C. Patel College of Pharmacy, Shirpur.

22

Main Points to be CoveredMain Points to be Covered

History History

Concept of Alternative Concept of Alternative

Ethics Ethics

Uses of 3R and alternative Uses of 3R and alternative

Globalization of R- ConceptGlobalization of R- Concept

Do they work?Do they work?

Organization Organization

33

History History (1,2)(1,2)

Galen, a physician in second-century Rome dissected pigs and Galen, a physician in second-century Rome dissected pigs and goats, and is known as the "goats, and is known as the "father of vivisectionfather of vivisection" "

1880- Louis Pasteur convincingly demonstrated the germ 1880- Louis Pasteur convincingly demonstrated the germ theory of medicine by giving anthrax to sheep.theory of medicine by giving anthrax to sheep.

1890- Ivan Pavlov famously used dogs to describe classical 1890- Ivan Pavlov famously used dogs to describe classical conditioning. Insulin was first isolated from dogs in 1922 conditioning. Insulin was first isolated from dogs in 1922

1957- a Russian dog became the first of many animals to orbit 1957- a Russian dog became the first of many animals to orbit the earth.the earth.

44

The purpose of animal experiments The purpose of animal experiments (1,15,3)(1,15,3)

1.1. The use of animal testing in the development and quality The use of animal testing in the development and quality control of products for human and veterinary healthcare. control of products for human and veterinary healthcare.

2 2 To increase our fundamental scientific knowledge.To increase our fundamental scientific knowledge.

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Facts and figures on animal experiments Facts and figures on animal experiments (14)(14)

100 million animals are experimented every year, The 100 million animals are experimented every year, The British Union for the Abolition of Vivisection (BUAV) British Union for the Abolition of Vivisection (BUAV)

10–11 million of them in the European Union10–11 million of them in the European Union 25 million are used in USA25 million are used in USA

Council on Bioethics reports, 50 to 100 million vertebrate Council on Bioethics reports, 50 to 100 million vertebrate animals used annually worldwide.animals used annually worldwide.

According to USDA's figures :-1,177,566 animals used in According to USDA's figures :-1,177,566 animals used in 2005.2005.

66

77

Introduction of alternative Introduction of alternative (1,4,15)(1,4,15)

In 1842 British Society for the In 1842 British Society for the Prevention of Cruelty to AnimalsPrevention of Cruelty to Animals

In 1959 W.M.S. Russell and R.L. In 1959 W.M.S. Russell and R.L. Burch published their book- Burch published their book-

The Principles of Humane The Principles of Humane Experimental TechniqueExperimental Technique

IN 1954 :- Universities IN 1954 :- Universities Federation for Animal Welfare Federation for Animal Welfare (UFAW) in the UK.(UFAW) in the UK.

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Replacement:Replacement: Methods that permit a given Methods that permit a given

purpose to be achieved without purpose to be achieved without conduction experiments or other conduction experiments or other scientific procedures on vertebrate scientific procedures on vertebrate animals. animals.

Reduction:Reduction: Methods for obtaining comparable Methods for obtaining comparable

levels of information from the use levels of information from the use of fewer animals in scientific of fewer animals in scientific procedures, or for obtaining more procedures, or for obtaining more information from the same number information from the same number of animals.of animals.

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Refinement:Refinement: Methods that alleviate or Methods that alleviate or minimise pain, suffering and minimise pain, suffering and distress, and which enhance distress, and which enhance animal well-being.animal well-being.

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Rules in India :- Rules in India :-

Prevention of Cruelty to Animal Act, 1960.Prevention of Cruelty to Animal Act, 1960.

CPCSEA Guide lines.CPCSEA Guide lines.

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The objectives of this module are The objectives of this module are (1,4,15)(1,4,15)

To discuss the Three Rs as they were defined by Russell and To discuss the Three Rs as they were defined by Russell and Burch in 1959 Burch in 1959

To introduce the concept of alternatives in To introduce the concept of alternatives in Research, Research, Teaching and TestingTeaching and Testing..

To discuss the potentials and limitations of alternatives To discuss the potentials and limitations of alternatives

To consider examples of alternatives and how they may be To consider examples of alternatives and how they may be usedused

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Alternative Methodologies Alternative Methodologies (15)(15)

Alternative technology :-Alternative technology :- Economy :- time Economy :- time cost cost no. of animals usedno. of animals used

Stress = DISTRESS.Stress = DISTRESS.

1313

• Animal ModelsAnimal Models• Animal Testing alternative (s)Animal Testing alternative (s)• In vitro (method, In vitro (method, model, model,

technique)technique)• Non-animal alternative (s)Non-animal alternative (s)

Cell CultureCell CultureTissue CultureTissue CultureOrgan CultureOrgan Culture

• Single-cell OrganismsSingle-cell OrganismsInvertebratesInvertebrates

• FishFish• Simulator (s)Simulator (s)• Mannequin (s)Mannequin (s)• Mathematical Mathematical

Model (s)Model (s)

• Computer-interfaced Computer-interfaced InteractiveInteractiveDigital Image LibrariesDigital Image LibrariesVirtual SurgeryVirtual SurgeryVirtual Reality Virtual Reality

• Computer Computer simulation (s) simulation (s) Computer program (s)Computer program (s)Computer SoftwareComputer SoftwareComputer Aided Instruction Computer Aided Instruction 

• Physiological Simulation (s)Physiological Simulation (s) Videodisc (s)Videodisc (s)

Video display Video display Video (s) Video (s)

1414

ReplacementReplacement 11.Using of living system.Using of living system In vitro TechniquesIn vitro Techniques Invertebrates AnimalsInvertebrates Animals Micro-organismsMicro-organisms2. 2. Using Non-living systemsUsing Non-living systems Chemical TechniqueChemical Technique Physical/Mechanical SystemsPhysical/Mechanical Systems3. 3. Use of computer simulationUse of computer simulation

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ReductionReduction 1.1. Animal Sharing Animal Sharing 2.2. Improved StatisticalImproved Statistical3.3. Phylogenetic ReductionPhylogenetic Reduction4.4. Better Quality AnimalBetter Quality Animal5.5. Post-Marketing Surveillance Post-Marketing Surveillance 6.6. Autopsies and Biopsies Autopsies and Biopsies 7.7. Epidemiological Studies Epidemiological Studies

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RefinementRefinement 1.1. Decreased InvasivenessDecreased Invasiveness2.2. Improved Instrumentation Improved Instrumentation 3.3. Improved Control Pain Improved Control Pain 4.4. Improved Control of techniquesImproved Control of techniques

1717

Use of living SystemsUse of living Systems 1.1. In vitro Techniques-In vitro Techniques- Non animal living systems Non animal living systems There are three types:-There are three types:- Cell culture, Tissue culture, Organ cultureCell culture, Tissue culture, Organ culture Greatest control of test subject environment.Greatest control of test subject environment. Eg. – SkintexEg. – Skintex An in-vitro method to assess skin irritancy that uses pumpkin An in-vitro method to assess skin irritancy that uses pumpkin

rind to mimic the reaction of a foreign substance on human rind to mimic the reaction of a foreign substance on human skin.skin.

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EytexEytex National Testing Corp. in Palm Springs,National Testing Corp. in Palm Springs, Is an in-vitro (test-tube) procedure that measures eye irritancy Is an in-vitro (test-tube) procedure that measures eye irritancy

via a protein alteration system. A vegetable protein from the via a protein alteration system. A vegetable protein from the jack bean mimics the reaction of the cornea to an alien jack bean mimics the reaction of the cornea to an alien substance.substance.

Alternative to -Alternative to -Draize eye irritancy test.Draize eye irritancy test.

Some factors are responsible :- Some factors are responsible :- Atmosphere HumidityAtmosphere Humidity Temperature PTemperature PHH

NutrientsNutrients

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Invertebrate Animals :-Invertebrate Animals :-

More commonly used laboratory animals.More commonly used laboratory animals. 90% of animals are invertebrates 90% of animals are invertebrates Example- fruit fly, Example- fruit fly, Drosophila melanogaster.Drosophila melanogaster. Uses- Study of genetics, Mutagenicity, teratogenicity, and reproductive Uses- Study of genetics, Mutagenicity, teratogenicity, and reproductive

toxicity.toxicity. Marine Invertebrates – are different species and used to study the Marine Invertebrates – are different species and used to study the

physiology of Nervous System.physiology of Nervous System.

2020

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Micro-OrganismsMicro-Organisms

Use to replace the animal modelsUse to replace the animal models Example – Example – Ames testAmes test – used for carcinogenicity/ mutagenicity – used for carcinogenicity/ mutagenicity

–by using –by using Salmonela typhimurium.Salmonela typhimurium. Allow limit less compounds to be tested which create an Allow limit less compounds to be tested which create an

interesting dilemmainteresting dilemma Also used for the screening process.Also used for the screening process. Agarose Diffusion Method.Agarose Diffusion Method.

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Using Non-living systemsUsing Non-living systems

1.1. Chemical techniques :- Chemical techniques :- Chromatographic Chromatographic and and spectroscopicspectroscopic.. Immunochemical techniquesImmunochemical techniques use for binding capacity of use for binding capacity of

highly specific antibodies to seek out minute quantities of highly specific antibodies to seek out minute quantities of antigen antigen

Eg.-Eg.- Technique to identify bacterial toxins -- which save several Technique to identify bacterial toxins -- which save several mice.mice.

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ELISA :-ELISA :- Home pregnancy detection Home pregnancy detection Previously it done by over- Previously it done by over-

the-counter test kit.the-counter test kit. Required no. of Rabbits.Required no. of Rabbits.

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Physical/mechanical SystemsPhysical/mechanical Systems Used of computer-linked mannequinsUsed of computer-linked mannequins Use in EpidemiologyUse in Epidemiology CAT, MRI, PET and SPECTCAT, MRI, PET and SPECT

2525

Use of Computer SimulationUse of Computer Simulation

Computer simulation-Computer simulation- QSARQSAR - Identification of particular chemical structure – - Identification of particular chemical structure –

shows potential reactivity – so resulting toxicity can be shows potential reactivity – so resulting toxicity can be determine.determine.

TOPKATTOPKAT computer software program computer software program measures toxicity, mutagenicity, carcinogenicity, and measures toxicity, mutagenicity, carcinogenicity, and

teratonogenicityteratonogenicity

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Picture presentation of IV injection Picture presentation of IV injection

2727

Reduction Reduction The IACUC can determine experimental design was employed to The IACUC can determine experimental design was employed to

minimize overall animal use. Methods to achieve this include: minimize overall animal use. Methods to achieve this include: 1.1. Pilot studies. Pilot studies. 2.2. Designing a study to utilize animals as their own controls. Designing a study to utilize animals as their own controls. 3.3. Gathering a maximum amount of information from each animal.Gathering a maximum amount of information from each animal.4.4. Consulting with a statistician. Consulting with a statistician. 5.5. Minimizing variables Minimizing variables 6.6. To ensure that experiments are not duplicated. To ensure that experiments are not duplicated. 7.7. Using the appropriate species of animal so that useful data is Using the appropriate species of animal so that useful data is

collected. collected.

2828

Animal SharingAnimal Sharing :- :- Significantly reduce the no. of use animals.Significantly reduce the no. of use animals.

Eg.- Eg.- SurgicalSurgical approach on an animal that has been, or is to be approach on an animal that has been, or is to be euthanatizedeuthanatized for other purposes, or providing organs or for other purposes, or providing organs or tissues at the time of tissues at the time of necropsy.necropsy.

If within same institute, perform same test, the control can be If within same institute, perform same test, the control can be take common.take common.

2929

Improved Statistical DesignImproved Statistical Design Consulting with the statistician during the design phase Consulting with the statistician during the design phase

A design strategies-A design strategies- Eg.- Eg.- Group sequential testing, and Crossover designs.Group sequential testing, and Crossover designs.

Low cost statistical packages for computer Low cost statistical packages for computer

3030

Phylogenetic ReductionPhylogenetic Reduction Designed to use one of the myriad of invertebrate species Designed to use one of the myriad of invertebrate species

instead of a non-human primate.instead of a non-human primate.

The animals chosen for project usage should be the least The animals chosen for project usage should be the least advanced from a phylogenetic standpoint.advanced from a phylogenetic standpoint.

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Better Quality AnimalsBetter Quality Animals

When purchasing laboratory animals-cost and quality are When purchasing laboratory animals-cost and quality are usually directly correlated. usually directly correlated.

The best quality animals, in terms of genetic status. The best quality animals, in terms of genetic status. Institutional commitment of institute. Institutional commitment of institute. Animals of different or unknown health status should never Animals of different or unknown health status should never

share the same.share the same.

3232

Post-Marketing SurveillancePost-Marketing Surveillance

Autopsies and Biopsies Autopsies and Biopsies

Epidemiological StudiesEpidemiological Studies

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RefinementRefinement

1.1. Identifying pain and distress and making plans for reliving it. Identifying pain and distress and making plans for reliving it. 2.2. Setting the earliest possible endpoint for the experiment.Setting the earliest possible endpoint for the experiment.3.3. Receiving adequate training prior to performing a procedure. Receiving adequate training prior to performing a procedure. 4.4. Using proper handling techniques for animals. Using proper handling techniques for animals. 5.5. Ensuring that drug doses are correct and are not expired. Ensuring that drug doses are correct and are not expired. 6.6. Ensuring that procedures to be performed on the animal are Ensuring that procedures to be performed on the animal are

reasonable for that species. reasonable for that species. 7.7. Performing surgeries and procedures aseptically to prevent Performing surgeries and procedures aseptically to prevent

infection.infection.

3434

8.8. Using appropriate analgesics and anesthetics for potentially painful Using appropriate analgesics and anesthetics for potentially painful procedures. procedures.

9.9. Performing only a single major survival surgery on any one animal, Performing only a single major survival surgery on any one animal, whenever possible. whenever possible.

10. 10. Performing appropriate post-surgical care, including thermoregulation Performing appropriate post-surgical care, including thermoregulation and fluid balance. and fluid balance.

11. 11. There are several specific research techniques in common use that are There are several specific research techniques in common use that are often criticized for their potential for causing pain or distress to often criticized for their potential for causing pain or distress to animals. animals.

3535

Decreased InvasivenessDecreased Invasiveness The use of The use of Magnetic Resonance Imaging-Magnetic Resonance Imaging- formerly required formerly required

euthanasia of multiple animals along a time curve to obtain euthanasia of multiple animals along a time curve to obtain assay tissue. assay tissue.

One animal can provide all the information along a given One animal can provide all the information along a given curve- curve- Vascular Access DeviceVascular Access Device - repeated samples or - repeated samples or injections in a single animal instead of using several animals. injections in a single animal instead of using several animals.

3636

Improved InstrumentationImproved Instrumentation Monitoring AnimalsMonitoring Animals – – Microelectronics, fiber optics and laser instrumentation, the Microelectronics, fiber optics and laser instrumentation, the

potential for refining techniques.potential for refining techniques.Improved instrumentation - reducing the level of restraint and/or Improved instrumentation - reducing the level of restraint and/or

manipulation necessary to obtain biological samples.manipulation necessary to obtain biological samples.The use of tethers in a variety of species to allow continuous The use of tethers in a variety of species to allow continuous

access to the various organ systems.access to the various organ systems.

Advantages -Advantages - minimizing a variety of non experimental minimizing a variety of non experimental variables associated with prolonged restraint. variables associated with prolonged restraint.

3737

Analyzing Samples –Analyzing Samples – The available diagnostic laboratory equipment which require The available diagnostic laboratory equipment which require

only micro liter blood samples to perform a variety of only micro liter blood samples to perform a variety of diagnostic tests.diagnostic tests.

The use of smaller sample sizes permits the use of smaller The use of smaller sample sizes permits the use of smaller animal species and prevents the need to euthanatize many of animal species and prevents the need to euthanatize many of these species to obtain the necessary volume of bloodthese species to obtain the necessary volume of blood

It is now possible to obtain serial blood samples from small It is now possible to obtain serial blood samples from small laboratory rodents which reduces the number of animals. laboratory rodents which reduces the number of animals.

3838

Improved Control of PainImproved Control of Pain The Animal Welfare Act requires -"that the principal The Animal Welfare Act requires -"that the principal

investigator consider alternatives to any procedure likely to investigator consider alternatives to any procedure likely to produce pain or distress in an experimental animal.“produce pain or distress in an experimental animal.“

Use of tranquilizers, analgesics and anesthetics.Use of tranquilizers, analgesics and anesthetics.

3939

Improved Control of TechniquesImproved Control of Techniques The handling and restraint of animalsThe handling and restraint of animals Animals can be trained or conditioned to accept a variety of Animals can be trained or conditioned to accept a variety of

procedures.procedures. It's inexpensive, readily portable, safe even at the highest It's inexpensive, readily portable, safe even at the highest

doses and spreads rapidly through the staff. doses and spreads rapidly through the staff. This can be the veterinarian, a member of the animal care staff This can be the veterinarian, a member of the animal care staff

or a fellow investigator. or a fellow investigator.

4040

Globalization of R- concept Globalization of R- concept (6,7)(6,7)

Dr. David B. MortonDr. David B. Morton, expanded this concept to the , expanded this concept to the Fifteen Fifteen R'sR's :- :-

1.1. Reduce Reduce the number used. the number used. 2.2. RefineRefine end points and procedures. end points and procedures. 3.3. ReplaceReplace with with in vitro, ex vitroin vitro, ex vitro methods when possible. methods when possible.

4141

4 4 Respect Respect all animals regardless of species all animals regardless of species. . 5 5 Recognize Recognize any adverse effects. any adverse effects. 66 RelieveRelieve pain with analgesics, distress with anxiolytics. pain with analgesics, distress with anxiolytics. 77 RefuseRefuse to carry out some procedures if concerned. to carry out some procedures if concerned. 88 Reconsider Reconsider protocol if unsure. protocol if unsure.99 ReadRead about the science and the ethical issues. about the science and the ethical issues.1010 Reflect Reflect on the work you have carried out. on the work you have carried out. 1111 ReasonReason out why you are doing the research out why you are doing the research1212 RecordRecord all your observations carefully. all your observations carefully. 1313 RewardReward rather than cause harm and for happiness. rather than cause harm and for happiness. 1414 Reappraise Reappraise techniques for efficacy. techniques for efficacy.

1515 ResolveResolve to learn new techniques to learn new techniques. .

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Search Strategy Search Strategy (8, 14,15)(8, 14,15) Have a clear understanding of the objectives and methods of Have a clear understanding of the objectives and methods of

the proposed study the proposed study

Choose appropriate databases based upon the protocol.Choose appropriate databases based upon the protocol.

Develop the literature search strategy.Develop the literature search strategy.

Execute the search. Execute the search.

4343

Communication between the investigator and the Communication between the investigator and the information specialist - information specialist -

1.1. General area of study.General area of study.2.2. Species.Species.3.3. Briefly describe your experimental protocol. Briefly describe your experimental protocol. 4.4. Specific systems or parts of the anatomy are involved.Specific systems or parts of the anatomy are involved.5.5. Give correct spellings of these structures and any acronyms.Give correct spellings of these structures and any acronyms.6.6. If you are studying the effects of a particular hormone, If you are studying the effects of a particular hormone,

enzyme, or chemical agent, give the complete spelling of the enzyme, or chemical agent, give the complete spelling of the compound as well as its trade name and acronym.compound as well as its trade name and acronym.

7.7. Do you know of any prominent authors in your area of Do you know of any prominent authors in your area of research?research?

8.8. Have you published any previous literature that relates to Have you published any previous literature that relates to your current study? your current study?

9.9. What makes your study unique from previous studies?What makes your study unique from previous studies?

4444

DATA BASES DATA BASES (15, 11)(15, 11)

AGRICOLAAGRICOLA ALTBIB ALTBIB ALTWEBALTWEB MEDLINE MEDLINE AGRISAGRIS ASFAASFA AVLINE A-V ONLINE AVLINE A-V ONLINE BIOETHICSLINE BIOETHICSLINE BIOSIS PREVIEWS BIOSIS PREVIEWS CABI Center CABI Center CAB ABSTRACTS CAB ABSTRACTS CEBA CEBA

CRIS/USDA CRIS/USDA CRISP CRISP CURRENT CONTENTS CURRENT CONTENTS

and UNCOVERand UNCOVER EMBASE ERICEMBASE ERIC FEDERAL REGISTER FEDERAL REGISTER

Provider Provider FISHERIES REVIEW FISHERIES REVIEW WILDLIFE REVIEW WILDLIFE REVIEW

Based Based ZOOLOGICAL RECORD ZOOLOGICAL RECORD

ONLINE ONLINE LEGI-SLATELEGI-SLATE

4545

LIFESCIENCES COLLECTION LIFESCIENCES COLLECTION MAGAZINE ASAP/MAGAZINE INDEX MAGAZINE ASAP/MAGAZINE INDEX MICROCOMPUTER SOFTWARE GUIDE MICROCOMPUTER SOFTWARE GUIDE PNI PNI TOXNET TOXNET PHILOSOPHER'S INDEX PHILOSOPHER'S INDEX PIC PIC PsychINFOPsychINFO

4646

AGRICOLA –AGRICOLA – Covers every major agricultural subject, including agricultural Covers every major agricultural subject, including agricultural

engineering and marketing, animal breeding, entomology, engineering and marketing, animal breeding, entomology, environmental pollution, etc.environmental pollution, etc.

AGRICOLA Thesaurus for Animal Use Alternatives AGRICOLA Thesaurus for Animal Use Alternatives ALTBIBALTBIB – – Is to assist in identifying methods and procedures helpful in Is to assist in identifying methods and procedures helpful in

supporting the development, testing, application, and supporting the development, testing, application, and validation of alternatives to the use of vertebrates in validation of alternatives to the use of vertebrates in biomedical research and toxicology testing. biomedical research and toxicology testing.

Biological AbstractsBiological Abstracts – – Worldwide journal literature in the life sciences including Worldwide journal literature in the life sciences including

biochemistry, biophysics, experimental medicine, veterinary biochemistry, biophysics, experimental medicine, veterinary science, virology, and other topics.science, virology, and other topics.

4747

EMBASE –EMBASE – A large biomedical and pharmaceutical database with extensive A large biomedical and pharmaceutical database with extensive

international coverage of drug research, pharmacology, international coverage of drug research, pharmacology, toxicology, environmental health, clinical and experimental toxicology, environmental health, clinical and experimental human medicine, and other topics. human medicine, and other topics.

PsycINFO – PsycINFO – Worldwide literature in psychology and related disciplines. Worldwide literature in psychology and related disciplines.

Includes research on experimental human and animal Includes research on experimental human and animal psychology, physiological psychology, and behavioral research.psychology, physiological psychology, and behavioral research.

Information on Alternatives Databases –Information on Alternatives Databases – Produced by the Norwegian Reference Centre for Laboratory Produced by the Norwegian Reference Centre for Laboratory

Animal Science and Alternatives. Describes databases Animal Science and Alternatives. Describes databases addressing all aspects of Replacement, Reduction, and addressing all aspects of Replacement, Reduction, and Refinement of animal experiments. Refinement of animal experiments.

4848

Altweb – Altweb – material and news about all aspects of alternatives in animal material and news about all aspects of alternatives in animal

research.. Current Research Information System (CRIS) Lists research.. Current Research Information System (CRIS) Lists USDA-sponsored projects. USDA-sponsored projects.

Guide To Searching for Alternatives to the Use of Laboratory Guide To Searching for Alternatives to the Use of Laboratory Animals Animals

FRAME (Fund for the Replacement of Animals in Medical FRAME (Fund for the Replacement of Animals in Medical Experiments) Experiments)

4949

Organization Organization (6,7, 8,15)(6,7, 8,15) Alternatives Search Service – Alternatives Search Service – Alternatives to Skin Irritation Testing in AnimalsAlternatives to Skin Irritation Testing in Animals ALTWEBALTWEB Animal Welfare Information CenterAnimal Welfare Information Center Center for Animal Welfare Center for Animal Welfare Centre for the Study of Animal Welfare (CSAW), University Centre for the Study of Animal Welfare (CSAW), University

of Guelph of Guelph European Centre for the Validation of Alternative Methods European Centre for the Validation of Alternative Methods

(ECVAM)(ECVAM) Information on Alternatives Databases - hosted by the Information on Alternatives Databases - hosted by the

Norwegian Reference Centre for Laboratory Animal Science Norwegian Reference Centre for Laboratory Animal Science and Alternatives. and Alternatives.

Model Organisms for Biomedical Research - Mammalian and Model Organisms for Biomedical Research - Mammalian and non-mammalian; Funding Opportunities. National Institutes of non-mammalian; Funding Opportunities. National Institutes of Health. Health.

5050

UVA Institutional Animal Care & Use Committee (IACUC)UVA Institutional Animal Care & Use Committee (IACUC) Animal Welfare Information Center (AWIC) National Animal Welfare Information Center (AWIC) National

Agricultural Library Agricultural Library European Centre for the Validation of Alternative Methods European Centre for the Validation of Alternative Methods

(ECVAM) (ECVAM) Fund for the Replacement of Animals in Medical Experiments Fund for the Replacement of Animals in Medical Experiments

(FRAME)(FRAME) Institutional Animal Care and Use Committee Training and Institutional Animal Care and Use Committee Training and

Learning ConsortiumLearning Consortium Interagency Coordinating Committee for the Evaluation of Interagency Coordinating Committee for the Evaluation of

Alternative Methods Alternative Methods Johns Hopkins Center for Alternatives to Animal Testing Johns Hopkins Center for Alternatives to Animal Testing

(CAAT) (CAAT) Laboratory Animal Welfare Training Exchange Laboratory Animal Welfare Training Exchange Netherlands Center Alternatives to Animal Use (NCA)Netherlands Center Alternatives to Animal Use (NCA) NORINA (Norwegian Inventory of Alternatives) NORINA (Norwegian Inventory of Alternatives) Model Organisms for Biomedical Research Model Organisms for Biomedical Research University of California Center for Animal Alternatives University of California Center for Animal Alternatives

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ReferencesReferences

1.1. Animal Testing AlternativesAnimal Testing Alternatives,, by Karen Lee Stevens, by Karen Lee Stevens, Founder & President ALL FOR ANIMALS®. All rights Founder & President ALL FOR ANIMALS®. All rights reserved.reserved.

2.2. Animal Resources and Procedures HandbookAnimal Resources and Procedures HandbookUniversity of Kentucky, ETHICS AND HUMANE University of Kentucky, ETHICS AND HUMANE CONSIDERATIONS, ALTERNATIVES TO ANIMAL CONSIDERATIONS, ALTERNATIVES TO ANIMAL EXPERIMENTATION.EXPERIMENTATION.

3.3. U.S. Department of Agriculture (USDA), NATIONAL U.S. Department of Agriculture (USDA), NATIONAL AGRICULTURE LIBRARY, ANIMAL INFORMATION AGRICULTURE LIBRARY, ANIMAL INFORMATION CENTER.CENTER.

4.4. MSU animal used and care, GUIDELINES FOR MSU animal used and care, GUIDELINES FOR ALTERNATIVES SEARCHING.ALTERNATIVES SEARCHING.

5.5. S G Lisansky and R Macmillan, Alternatives to Animal S G Lisansky and R Macmillan, Alternatives to Animal Testing,Testing, CPL Press  1996,388 Pages  ISBN 1872691463  CPL Press  1996,388 Pages  ISBN 1872691463          

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6.6. Alternatives to Animal Testing: Research, Trends, Alternatives to Animal Testing: Research, Trends, Validation, Regulatory Acceptance (Download: Part 1, Part Validation, Regulatory Acceptance (Download: Part 1, Part 2, Part 3) Jane Huggins Toxicology Consulting Services, 2, Part 3) Jane Huggins Toxicology Consulting Services, USA-Plainsboro.USA-Plainsboro.

7.7. ALAN M. GOLDBERG, L.F.M. van ZUTPHEN ALAN M. GOLDBERG, L.F.M. van ZUTPHEN Mary Ann Mary Ann Liebert, IncLiebert, Inc Alternative Methods in Toxicology, Volume 11 Alternative Methods in Toxicology, Volume 11 - The World Congress on Alternatives and Animal Use in - The World Congress on Alternatives and Animal Use in the Life Sciences: Education, Research,the Life Sciences: Education, Research,..

8.8. Richard L. Summers, Steve M. Hudson, and Jean-Pierre Richard L. Summers, Steve M. Hudson, and Jean-Pierre Montana,Montana, Department of Emergency Medicine and the Department of Emergency Medicine and the Department of Physiology, University of Mississippi Department of Physiology, University of Mississippi Medical Center, Jackson, Mississippi, Animal Welfare Medical Center, Jackson, Mississippi, Animal Welfare Information Center Newsletter, Winter 1995/1996, Vol. 6 Information Center Newsletter, Winter 1995/1996, Vol. 6 No. 2-4 No. 2-4

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88 C. Hendriksen, J. Rozing, M. van der Kamp, W. de Leeuw, C. Hendriksen, J. Rozing, M. van der Kamp, W. de Leeuw, "The production of monoclonal antibodies: Are animals still "The production of monoclonal antibodies: Are animals still needed?" needed?" Alternatives to Laboratory Animals,Alternatives to Laboratory Animals, 1996;24:109- 1996;24:109-110.110.

99 I.D. Bross, "Mathematical models vs. animal models," I.D. Bross, "Mathematical models vs. animal models," Perspectives on Animal ResearchPerspectives on Animal Research, 1989; 1:83-108; L. , 1989; 1:83-108; L. Blumenson, I. Bross, "A mathematical analysis of the Blumenson, I. Bross, "A mathematical analysis of the growth and spread of breast cancer," growth and spread of breast cancer," BiometricsBiometrics, , 1969;25:95-109. 1969;25:95-109.

1010 Norina Database http://oslovet.veths.no/NORINA/Norina Database http://oslovet.veths.no/NORINA/1111 European Resource Centre for Alternatives (EURCA) European Resource Centre for Alternatives (EURCA)

http://www.eurca.org/http://www.eurca.org/1212 The Principles of Humane Experimental Technique W.M.S. The Principles of Humane Experimental Technique W.M.S.

Russell and R.L. Burch Methuen & Co. Ltd. London 1959. Russell and R.L. Burch Methuen & Co. Ltd. London 1959. (Special Edition publ. by Universities Federation for Animal (Special Edition publ. by Universities Federation for Animal Welfare, 1992) Welfare, 1992) http://altweb.jhsph.edu/publications/humane_exp/het-http://altweb.jhsph.edu/publications/humane_exp/het-toc.htmtoc.htm

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13.13. Balls, M., Goldberg, A.M., Fentem, J.H. et al (1995) The Balls, M., Goldberg, A.M., Fentem, J.H. et al (1995) The three Rs: The way forward: ECVAM Workshop Report 11. three Rs: The way forward: ECVAM Workshop Report 11. ATLA 23: 838-866 ATLA 23: 838-866 http://www.ccac.ca/en/CCAC_Programs/ETCC/Module03/0http://www.ccac.ca/en/CCAC_Programs/ETCC/Module03/08.html8.html

14.14. Rown A.N., Stratmann C.J.; The use of alternatives in Rown A.N., Stratmann C.J.; The use of alternatives in DRUG RESEACH ; The mechmillan Press Ltd. Delhi;148-DRUG RESEACH ; The mechmillan Press Ltd. Delhi;148-151.151.

15.15. CRCA (Chancellor’s Animal Research Committee ) USDA CRCA (Chancellor’s Animal Research Committee ) USDA INFORMATIONAL REQUIREMENTS.INFORMATIONAL REQUIREMENTS.

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