The Gustave L. and Janet W. Levy Library

Search for Alternatives to Animal Testing and Research

Introduction
Any use of animals by Mount Sinai faculty in research and teaching must first be reviewed and approved by the Institutional Animal Care and Use Committee (IACUC). As a part of the review process, the committee must determine that the principal investigator has met the "information requirements" under the USDA Animal Welfare Act (AWA) and regulations interpreting that act. The USDA Animal Care Resource Guide Policy #12 (.pdf) requires that:

• Investigator provide a written narrative description of the methods and sources used to consider alternatives to procedures that may cause more than momentary or slight pain or distress to the animals; and
• The written assurance that the activities do not unnecessarily duplicate
  previous experiments.

This guide provides researchers with search guidance and access to a variety databases to successfully meet the AWA's information requirements.

Research & Testing Alternatives:
Search Requirements

• The Three R's: Replacement, Reduction and Refinement
• Red Flags in IACUC Reviews

Research & Testing Alternatives:
Search Tips

• Search Strategies
• Search Vocabulary

Databases

• Research & Testing Alternatives:
  Comprehensive Databases
• Research & Testing Alternatives:
  Specialized Databases
• Research & Testing Alternatives:
  Animal Models
• Avoiding Duplication:
  Databases for Finding Unpublished or Ongoing Studies
• Educational Alternatives:
  Animal Use in Education

The USDA believes that the performance of a database search is the best method for demonstrating compliance with the requirement to consider alternatives to painful or distressful animal testing procedures. The search must be documented with:

• The names of the databases searched;
• The date the search was performed;
• The period covered by the search; and
• The key words and/or the search strategy used.

The Animal Welfare Information Center (AWIC), designated in the Animal Welfare Act as a resource for primary investigators searching for the availability of alternatives to animal testing, recommends using multiple databases to ensure comprehensive retrieval of literature on animal testing alternatives.

Mount Sinai investigators can obtain forms to document alternatives searches from the Mount Sinai Institutional Animal Care and Use Committee.

USDA Animal Care Resource Guide Policy #12 (pdf) defines alternatives or alternative methods as:

Those that incorporate some aspect of replacement, reduction, or refinement of animal use in pursuit of the minimization of animal pain and distress consistent with the goals of the research. These include methods that use non-animal systems or less sentient animal species to partially or fully replace animals (for example, the use of an in vitro or insect model to replace a mammalian model), methods that reduce the number of animals to the minimum required to obtain scientifically valid data, and methods that refine animal use by lessening or eliminating pain or distress and, thereby, enhancing animal well-being.

Replacement, reduction and refinement should be addressed in the literature search for alternatives.

In its Alternatives and the Animal Welfare Act Brochure (.pdf), the Animal Welfare Information Center (AWIC) lists six "red flags" that may cause concern during the IACUC review of the literature search. The red flags are listed below, next to solutions adapted from those offered by the Health Sciences Library at the New York Medical Center.

AWIC recommends conducting a two phase search for alternatives

• Phase 1: Reduction and Refinement
  During the planning phase of the research proposal, researchers must investigate animal use alternatives so that appropriate methods are incorporated into the experimental design from the outset. A comprehensive generalized database search provides a basic overview of current research, the techniques and species used, and may address unnecessary duplication. As the research proposal develops, more focused literature searches may retrieve information on methods that enable the investigator to reduce the number of animals used and to alleviate the animals' pain and distress.
• Phase 2: Replacement
  Alternative animal and non-animal models should be considered during the research planning phase, as well. A realistic evaluation of whether cell or tissue culture, models, simulations or animals lower on the phylogenetic scale can replace the proposed animals is possible only after the study objectives have been clarified.

Keywords, concepts and database selection will determine the investigator's ultimate search strategy. However, we can offer a few general suggestions for conducting a comprehensive literature search:

• Don't rely on a database to automatically search word variations, spelling variations or concepts related to the keywords that you enter.
  • Use truncation. In some databases, symbols such as the * or ? may be used at the end of a search term to retrieve variations of the original term. For example in MEDLINE via PubMed, cage* will search for records with the words cage, cages, caging, caged, etc.
  • Use American, British and European spellings variations.
  • Find out whether the database that you are using has a "controlled vocabulary" or thesaurus of indexing terms. If it does, look up the terms relevant to your main concepts and use them in your search. Examples of databases that offer a controlled vocabulary are MEDLINE (MeSH) and AGRICOLA (the NAL Thesaurus).
• Use connecting words (Boolean operators) such as AND, OR, NOT to combine concepts and to expand or narrow the search.
• It's easy to make a mistake in complex searches such as those for animal use alternatives. It's often more effective to search small strings of related search words, and then combine the subsets using the "history" feature available in many databases.
  • For example in MEDLINE via PUBMED, a searcher might search first for mice OR mouse OR rodent OR rodents, and then cage OR cages OR caging OR housing OR enrichment, and finally combine (AND) the two searches in the search history tab. This avoids the errors possible when typing the search terms into the single search string: ((mice OR mouse OR rodent OR rodents) AND (cage OR cages OR caging OR housing OR enrichment)).
• Record your search strategy. It's usually possible to copy your search strings from a search history page and paste it into a document. Then it will be available when you submit your Vertebrate Animal Proposal for IACUC review.

Search vocabulary should include keywords reflecting the main concepts of the study under consideration, e.g., the experimental outcomes, species names, systems or anatomical terms, substance names, and methods and procedures. It should also include the major concepts of the alternatives of which the investigator is aware, even if the researcher believes that they are not likely to be useful in the proposed study.

The NIH Library provides a Tip Sheet on Searching for Alternatives to Painful Procedures. (.pdf) that contains recommendations for keywords for alternative terms and concepts. The Fund for the Replacement of Animals in Experiments (FRAME) also provides Search Terms and Strategies.

NOTE: "Animal use alternatives" is a phrase used to index citations regarding alternatives in the AGRICOLA and MEDLINE databases. However it is not used to index alternative studies in other databases such as ISI Web of Science, PsycINFO and ERIC. Although useful, this phrase should never be the only strategy used to retrieve information on alternatives. It is used primarily to index studies that are about ethical issues in animal use and it is not always applied to relevant studies.

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Choose databases that are appropriate for the area of study, keeping in mind the type of protocol: research, teaching or testing. All databases listed below are available to Mount Sinai faculty, students and staff both on- and off-campus. Most are freely available on the Web; databases provided through the Levy Library and limited to Mount Sinai users are noted. A more complete list of databases which may be useful in searching for animal use alternatives is available from the Animal Welfare Information Center at the National Agriculture Library.

Animal Care Resource Guide Policy #12 (.pdf) states that a database search is usually the best method for demonstrating compliance with the requirement to consider alternatives to painful/distressful procedures. In highly specialized fields, however, "conferences, colloquia, subject expert consultants or other sources may provide information regarding alternatives in lieu of, or in addition to, a database search." See our guide to Online Sources for Information about Animal Testing Alternatives to access current, authoritative Web-based information and resources provided by governmental and not-for-profit organizations to enable improved animal care and use.

The databases for avoiding duplication listed below are included to assist researchers in finding animal studies that will not be retrieved in a general literature seach because they are unpublished or ongoing.

AGRICOLA (AGRICultural OnLine Access)
http://agricola.nal.usda.gov/

AGRICOLA is a core database in the search for animal use alternatives. This is demonstrated by a search of the single phrase animal use alternatives, which retrieves over 1000 entries!

AGRICOLA serves as the catalog and index to the collections of the National Agricultural Library, as well as a primary public source for world-wide access to agricultural information. It includes citations to publications encompassing all aspects of agriculture and allied disciplines, including animal sciences. It is organized into two bibliographic data sets which may be searched separately or together :

• The NAL Online Public Access Catalog contains citations to books, audiovisuals,serials, and other materials, most of which are in the Library's collection.
• The Article Citation Database includes citations, many with abstracts, to journal articles, book chapters, reports, and reprints, selected primarily from the materials found in the NAL Catalog.

Searching AGRICOLA
Unlike some databases or search engines, AGRICOLA does not automatically employ "mapping" or "stemming" to find synonyms or related concepts for search terms. It also does not search subsidiary concepts ("explode") if broader indexing terms are used. To search AGRICOLA effectively:

• Employ synonyms, alternate spellings and variations of the words (such as tenses) in your search strategy.
• Consult the NAL Agricultural Thesaurus, an online vocabulary look-up tool for agricultural and biological terms. The Thesaurus is organized to help find terms in a specific discipline or subject area.
• It is also possible to browse the AGRICOLA Thesaurus for Animal Use Alternatives for over 200 subject headings that may be used as search terms.

The National Agricultural Library is an agency of the U.S. Department of Agriculture.

AltBib: Bibliography on Alternatives to Animal Testing
http://toxnet.nlm.nih.gov/altbib.html

AltBib is intended to assist in identifying methods and procedures helpful in supporting the development, testing, application, and validation of alternatives to the use of vertebrates in biomedical research and toxicology testing. It has three components:

• AltBib: This searchable bibliography on alternatives to the use of live vertebrates in biomedical research and testing was produced from MEDLINE database searches performed and analyzed by subject experts. It covers the years from 1980 through 2000.
• PubMed: A search interface which automatically searches Medline/PubMed using animal alternatives search filters. The AltBib interface also provides radio buttons that allows searchers to add "Animal Use Alternatives" as a phrase and MeSH term, search a toxicology subset, and/or limit the search to the years 2000 to present. Users can easily modify the automatic search filters.
• Live PubMed Searches on Selected Topics: AltBib allows searchers to run PubMed searches on fifteen broad topics and a range of subtopics. These searches are automatically limited to the years 2000 to present. AltBib's standardized searches can be refined in PubMed with search terms directly related to the investigators' protocol. They can also be modified in PubMed to retrieve citations prior to 2000.

AltBib is produced by the Toxicology and Environmental Health Information Program (TEHIP), which is a part of The Division of Specialized Information Services (SIS) of the National Library of Medicine (NLM).

Note: AltBib provides efficient tools to assist investigators in searching MEDLINE to find alternatives to animal testing. A comprehensive search for alternatives, however, must include databases (such as AGRICOLA, PsycINFO or ISI Web Of Science) in addition to MEDLINE.

ISI Web of Science via Web of Knowledge (with FindIt) (limited to Mount Sinai users)

Web of Science is a multidisciplinary database that contains citations and abstracts for the highest impact research journals in the world. It lacks the depth that AGRICOLA and MEDLINE offer in coverage of the literature of animal testing alternatives, but the breadth of its subject coverage can make it useful in uncovering core literature in the range of disciplines involved in animal research and the search for alternatives. Web of Science also has a unique cited reference searching feature that allows investigators to navigate backward in time using cited references to uncover the research that influenced an author's work, and to navigate forward in time to see how authors have built on an earlier work in later research.

MEDLINE via PubMed (with LinkOut and FindIt) (limited to Mount Sinai users)

MEDLINE is a core database in the search for animal use alternatives. A PubMed search with the phrase animal use alternatives returns over 1500 entries. The National Library of Medicine's premier bibliographic database, MEDLINE covers the journal literature in the fields of medicine, nursing, dentistry, veterinary medicine, and the preclinical science from the 1950s to present. PubMed is the Levy Library's preferred interface for searching PubMed.

MeSH is NLM's controlled vocabulary used for indexing articles for MEDLINE. PubMed searchers may consult the MeSH Database to identify search terms in specific disciplines or subject areas.

Although we believe that PubMed's automatic term mapping and other features facilitate effective, intuitive end-user searching, the Levy Library has licensed two other interfaces which Mount Sinai users may use search MEDLINE. Search results may vary from MEDLINE searches done in PubMed because each interface works differently to retrieve its results.

• MEDLINE via OVID Technologies- WebSPIRS (with FindIt) (limited to Mount Sinai users)
  Using the WebSPIRS interface, it is possible to search both MEDLINE and PsycINFO databases simultaneously.
• MEDLINE via Web of Knowledge (with FindIt) (limited to Mount Sinai users)
  The Web of Knowledge provides a "Cross Search" feature, so users can repeat searches done in MEDLINE in the Web of Science and INSPEC databases.

Medline via PubMed is also freely available at http://www.pubmed.gov.

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ALTWEB Humane Endpoints Database Search http://apps1.jhsph.edu/altweb/humane/search.cfm

AltWeb Humane Endpoints Database The Johns Hopkins Center for Alternatives to Animal Testing designed to help investigators find the earliest endpoint that is compatible with the scientific objectives of their research. An endpoint is "the point at which an experimental animal's pain and/or distress is terminated, minimized, or reduced by taking actions such as killing the animal humanely, terminating a painful procedure, or giving treatment to relieve pain and/or distress."

ALTWEB Pain Management (Anesthesia/Analgesia) Database
http://apps1.jhsph.edu/altweb/humane/search.cfm

The Johns Hopkins Center for Alternatives to Animal Testing citations about anesthesia and analgesia for most commonly used laboratory animals collected from the databases MEDLINE, TOXLINE, AGRICOLA, and AGRIS.

ECOTOX
http://mountain.epa.gov/ecotox

The Environmental Protections Agency's database ECOTOXicology provides single chemical toxicity information, and abstracted results for aquatic and terrestrial life. Its primary focus is wildlife species but the database does include information on domestic species. Priority is given to data published in the peer reviewed literature. Thesis, government reports and other grey literature are included in the databases. Computerized laboratory data files from the public sector and available unpublished reports are also acquired and critiqued.

INSPEC via Web of Knowledge (with FindIt) (limited to Mount Sinai users)

INSPEC is the world's largest bibliographic database in the field of physics, electrical engineering and electronics, computers and control engineering and information technology. Use INSPEC to find applications of artificial intelligence, robotics, computer simulation, neural networks, and cellular biophysics to studies that normally use animal models.

Invitroderm.com: Alternatives to Skin Irritation & Corrosion Testing in Animals
http://www.invitroderm.com

Browse or search a bibliography of about 360 abstracts about alternatives
to irritation and corrosion testing in animals.

MathSciNet (limited to Mount Sinai users)

MathSciNet provides access to experimental design techniques that may be used to reduce the number of animals necessary for testing.

PsycINFO via OVID Technologies- WebSPIRS (with FindIt) (limited to Mount Sinai users)

Use PsycInfo to find alternatives to the use of animals for studies on behavior, brain development, cognition, and other areas of research. PsycINFO is produced and copyrighted by the American Psychological Association and provides citations with abstracts to the scholarly literature in the psychological, social, behavioral, and health sciences. It provides indexing to approximately 1,300 journals, reports, various books and chapters, and U.S. dissertations (taken from Dissertation Abstracts).

Refinement and Environmental Enrichment for All Animals kept in Laboratories
http://www.awionline.org/lab_animals/biblio/Laball.htm

This database, a service of the Animal Welfare Institute, is a merger of two databases on refinement and environmental enrichment for animals kept in laboratories: the Primate Enrichment Database and the Laboratory Animal Refinement Database. It includes almost 4000 entries and 600 full text documents on all aspects of refinement of housing and handling conditions and environmental enrichment for all animals kept in research, testing and teaching institutions.

TOXNET: Toxicology Data Network
http://toxnet.nlm.nih.gov

TOXNET is a collection of over a dozen toxicology and environmental health databases that may be searched together from the TOXNET homepage. The databases may also be searched separately. Those of most interest to those searching for animal use alternatives include:

• TOXLINE
  TOXLINE records provide bibliographic information covering the biochemical, pharmacological, physiological, and toxicological effects of drugs and other chemicals. It contains over 3 million bibliographic citations, most with abstracts and/or indexing terms and CAS Registry Numbers.
• CCRIS: Chemical Carcinogenesis Research Information System
  A data bank developed and maintained by the National Cancer Institute (NCI). that contains over 8,000 chemical records with carcinogenicity, mutagenicity, tumor promotion, and tumor inhibition test results.
• DART/ETIC: Developmental and Reproductive Toxicology/Environmental Teratology Information Center
  A bibliographic database covering teratology and other aspects of developmental and reproductive toxicology. It contains over 100,000 references to literature published since 1965.
• GENE-TOX
  A toxicology data file that contains genetic toxicology (mutagenicity) test data, resulting from expert peer review of the open scientific literature, on over 3,000 chemicals. The GENE-TOX program was established to select assay systems for evaluation, review data in the scientific literature, and recommend proper testing protocols and evaluation procedures for these systems.
• HSDB:Hazardous Substances Data Bank
  Comprehensive, peer-reviewed toxicology data for about 5,000 chemicals. Chemical files include animal toxicity studies, human health effects, emergency medical treatment, chemical safety and handling and much more.

TOXNET is produced by the Toxicology and Environmental Health Information Program (TEHIP), which is a part of The Division of Specialized Information Services (SIS) of the National Library of Medicine (NLM),

Scientific Information Service (SIS) (beta)
http://ecvam-sis.jrc.it/

SIS is a database of the European Commission. It provides factual and evaluated information on advanced non-animal methods for toxicology assessments and offers full method descriptions, including development and validation status. SIS includes INVITTOX test protocols. Free registration is required to use the resources; some resources are not yet available online.

PrimateLit
http://primatelit.library.wisc.edu

The PrimateLit database provides bibliographic access to the scientific literature on nonhuman primates for the research and educational communities. Coverage spans 1940 to present and includes all publication categories (articles, books, abstracts, technical reports, dissertations, book chapters, etc.) and many subject areas (behavior, colony management, ecology, reproduction, field studies, disease models, veterinary science, psychology, physiology, pharmacology, evolution, taxonomy, developmental and molecular biology, genetics and zoogeography).

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ILAR Animal Models & Strains Search Engine
http://dels.nas.edu/ilar_n/ilarhome/search_amsst.shtml

The Institute for Laboratory Animal Research (ILAR) has developed a search engine which indexes and searches sites that sell or distribute animal models or strains of animals used for research.

The Jackson Laboratory Research Resources
http://www.jax.org/resources/index.html

Supports and provides access to a variety of tools related to mouse models in research such as:

• JAX® Mice Database
  Search by strain, gene, strain type, research application, or stock number. Strain Data Sheets include phenotypes, strain development, relevant controls, colony maintenance, associated references, genotyping protocols, and availability information.
• Mouse Genome Informatics
  Information on mouse genetic markers, molecular segments, phenotypes, comparative mapping data, experimental mapping data, and graphical displays for genetic, physical, and cytogenetic maps.
• IMSR: International Mouse Strain Resources
  A searchable online database of mouse strains and stocks available worldwide, including inbred, mutant, and genetically engineered mice.

Model Organisms for Biomedical Research
http://www.nih.gov/science/models

This site from the National Institutes of Health provides a clearinghouse for information about resources facilitating biomedical research using mice, rats, yeasts, neurospora, D.discoideum, round worms, fruit flies, zebra fish, frogs and arabidopsis.

ZFIN: The Zebrafish Information Network
http://zfin.org

ZFIN addresses zebrafish genetics and development via an online database of information for zebrafish researchers. ZFIN serves as the zebrafish model organism database.

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CRIS: Current Research Information Service
http://cris.csrees.usda.gov

CRIS, provided by the United States Department of Agriculture, contains information on ongoing and recently completed projects sponsored or conducted primarily within the USDA and State university research system. Some 30,000 project summaries, including latest progress reports and lists of recent publications coming out of the research, are maintained in the file on an ongoing basis.

Projects on human nutrition research of the Federal agencies are also included in the database. These are maintained in the Human Nutrition and Information Management System (HNRIMS) subfile. Updated annually, the HNRIMS subfile is prepared jointly by the U.S. Department of Agriculture and the National Institutes of Health (NIH), U.S. Department of Health and Human Services. The subfile currently contains some 4,000 summaries of human nutrition research projects conducted or sponsored by the USDA, NIH and other Federal agencies.

Search CRIS and the HNRIMS subfile using a fill-in form. A number of Help screens, automatic wildcarding, and built-in search logic are provided.

CRISP: Computer Retrieval of Information on Scientific Projects
http://crisp.cit.nih.gov

CRISP is a biomedical database system containing information on research projects and programs supported by the Department of Health and Human Services. Most of the research falls within the broad category of extramural projects, grants, contracts, and cooperative agreements conducted primarily by universities, hospitals, and other research institutions. CRISP contains Research and Development (R&D) awards from 1972 to present.

Projects included in CRISP have been funded by the National Institutes of Health (NIH) and other government agencies. A relatively small number of research grants are funded by the Centers for Disease Control and Prevention (CDC), the Food and Drug Administration (FDA), the Health Resources and Services Administration (HRSA), and the Agency for Health Care Research and Quality (AHRQ). CRISP also contains information on the intramural programs of the NIH and the FDA.

DoD Biomedical Research Database
http://www.dtic.mil/biosys/org/brd/index.htm
Search the Department of De fence Biomedical Research Database (BRD) for biomedical research, testing or training programs being federally funded in fiscal years 1998 through 2003.

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Alternatives in Education Database
http://www.avar.org/

The Association of Veterinarians for Animal Rights provides this database of alternatives to harming or killing nonhuman animals used in education.

eruca: The European Resource Centre for Alternatives in Higher Education
http://www.eurca.org/resources.asp

Eruca promotes the use of alternatives to using animals in higher education by hosting an database which includes full descriptions of the alternative teaching materials and methods. The pedagogical quality of alternative models is evaluated in a review process that takes into account support of the 3R’s concept; feasibility of implementation in higher education; interactive character; availability for evaluation, and the recommendations by experts in the field.

ERIC: The Education Resources Information Center
ERIC via CSA (limited to Mount Sinai users)
http://www.eric.ed.gov (freely available)

ERIC, sponsored by the Institute of Education Sciences (IES) of the U.S. Department of Education, produces the world’s premier database of journal and non-journal education literature. ERIC searches nearly 1.2 million citations going back to 1966 and provides access to more than 110,000 full-text materials at no charge.

InterNICHE
http://www.interniche.org/alt_loan.html#disc

The InterNICHE Alternatives Loan System is a library of multimedia CD-ROMs, videos, models and mannequins focusing on animal use and alternatives within the biological sciences, as well as in medical and veterinary education covering fields such as anatomy, physiology and surgery.

NORINA: A Norwegian Inventory of Audiovisuals
http://oslovet.veths.no/fag.aspx?fag=57

An English-language database containing information on over 3,800 audiovisual aids that may be used as alternatives or supplements to the use of animals in teaching. The database includes products developed around the world from 1991 to present. NORINA allows you to limit searches to free products and to products available by loan.

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