University of Virginia Health System

The Animal Welfare Act requires that all investigators using animals conduct a literature search for alternatives to painful procedures. (See: Animal Use Classification) This law applies to those animal projects categorized as Type C, D, or E. Make a note of the database searched, the years searched (at least 3 years since this is the time period for your protocol approval), and the keywords (including alternative) used. This information must be stated in your animal use protocol.

 Some available databases are:

AGRICOLA (AGRICultural OnLine Access)
a machine-readable database of bibliographic records created by the National AGRICultural Library and its cooperators. This database provides access to publications and other agricultural resources that include: plant and animal science, entomology, agricultural products, food and nutrition, agricultural trades, rural information, animal welfare, and several other categories. Book information and journal articles may be searched either via the web or if you're so equipped, a telnet interface.

NORINA
database for audiovisual alternatives for animals in teaching.

PUBMED
Nationals Library of Medicine MEDLINE database.

TBASE
The Transgenic/Targeted Mutation Database (TBASE): Since development of the technology to manipulate the germline of animals over a decade ago, a large number of transgenic animals have been produced worldwide for use in both basic and applied research. Additionally, development of gene targeting protocols involving homologous recombination in mouse embryonic stem cells has resulted in a considerable number of mutant lines with specific phenotypes and well-defined DNA structural changes. TBASE is an attempt to organize information on transgenic animals and targeted mutations generated and analyzed worldwide. TBASE is maintained by the Jackson Laboratory.

Centers Dedicated For Finding Alternatives:

Animal Welfare Information Center

John's Hopkins Center for Alternatives to Animal Testing

U. California- Davis Center for Animal Alternatives

Information Resources for Adjuvants and Antibody Production:

Comparisons and Alternative Technologies, Resource Series No. 3, March 1997, available from the Animal Welfare Information Center.

USDA Policy requires that the Institutional Animal Care and Use Committee (IACUC) be responsible for ensuring that investigators have appropriately considered alternatives to any procedures that may cause more than slight or momentary pain or distress. A written narrative description of the methods and sources used to search for alternatives must be provided.

A painful procedure is defined as any procedure that would reasonably be expected to cause more than slight or momentary pain and/or distress in an animal to which that procedure is applied. Where specific testing procedures are required by Federal law, the CFR references or other legal guidelines requiring them should be noted.

Animals exhibiting signs of pain, discomfort, or distress such as decreased appetite/activity level, decreased mobility, adverse reactions to physical contact, open sores/necrotic skin lesions, abscesses, lameness, conjunctivitis, corneal edema, and photophobia are expected to receive appropriate relief unless written scientific justification is provided in the animal use protocol and approved by the IACUC.

In the Animal Use Approval Form you are asked to classify how you will use the animals in your proposed study. Listed below are definitions for USDA Categories B through E.

CATEGORY B:
Animals being bred, conditioned, or held for use in teaching, testing, or research but not yet used for such purposes.

Examples include: breeding colonies, animals in behavioral observation studies, and animals purchased but not yet used by September 30 of the calendar year.

CATEGORY C:
Animals upon which studies were conducted involving no more than momentary pain, distress and have not needed administration of pain-relieving drugs.

Examples include: routine examinations, blood sampling, injection of non-toxic materials, approved methods of euthanasia that induce rapid unconsciousness, short periods (up to 24 hours) of withholding food and water, tail clipping and ear punching in mice < 4 weeks old. Animals that are euthanized and then have tissues/organs removed are included in Category C. Animals that are anesthetized and then have tissues/organs removed before euthanasia (e.g. perfusions) are in Category D.

CATEGORY D:
Studies involving more than momentary stress or pain, which is relieved by the use of appropriate anesthetic, analgesic, or tranquilizing drugs.

Examples include: invasive studies on anesthetized animals that may or may not regain consciousness, studies using noxious stimuli from which escape is possible, some tumor or device implants, the use of Freund's complete adjuvant for footpad injections, and food or water deprivation beyond that necessary for normal presurgical preparation. Freund's Complete Adjuvant used for antibody production may cause results ranging from momentary or slight pain to severe pain depending on the product, procedure, and species.

Terminal invasive procedures done on anesthetized animals before they are euthanized are included as Category D. Also included are studies in which disease or toxicity is induced and the animals are expected to become sick or abnormal.

Comment: Animals in Category D studies may show clinical symptoms of pain or distress as a result of the research objectives, but the necessary treatments to alleviate the symptoms are available and provided, or the animals are euthanized. Involvement of trained technicians, scientists, and veterinarians is critical if this pain is to be minimized or avoided. Adherence to acceptable veterinary practices is mandatory and will vary depending on the project, i.e. post-op analgesia, fluid therapy or intensive nursing care.

CATEGORY E:
Studies involving major stress or pain, or pain without the benefit of pain-relieving drugs (anesthesia, analgesia, tranquilizers).

Examples include: application of noxious stimuli from which escape is impossible; the use of muscle relaxants in surgery without concurrent use of anesthetics, induction of aggressive behavior leading to self-mutilation or fighting where death is the end-point. Also included are studies in which death is the end-point, i.e. diseases are induced and infected animals are permitted to succumb rather than be treated.

Comment: Animals are expected to show clinical symptoms of pain or distress as a result of the research objectives, but these symptoms cannot be treated or otherwise alleviated with the use of drugs or intensive care because doing so would interfere with the research objectives. Type E studies place an explicit responsibility on investigators to explore alternative designs to ensure that these methods have to be used. The reasons for using these procedures must be explained in a statement by the Principle Investigator, justifying their use. This statement is requested in the animal use protocol and is required by federal law. The IACUC submits this statement in its annual reports to the government.