Allen has stated that "[t]he publication of negative scientific results, use of alternatives terminology when abstracting journal articles or assigning keywords, and standardization of indexing terms for alternatives are several areas that would greatly benefit the search for alternatives." (1).
Additionally, Ungar has indicated that "the necessity to limit indexing terms to a manageable quantity places constraints on the number of facets that can be expressed. In our experience, when searching on the major databases, it is not really possible to identify with confidence publications that describe methodological advances [in the alternatives area]." (2).
Snow concurs by stating that "due to the 'principle of specificity in indexing, failure to include pertinent test names or methods terms, along with general keywords/codes illustrated here, may miss references to specific alternatives tests. (3)."
We lack a well-defined vocabulary of terms for alternatives to animal testing, and we do not consistently incorporate methodology terms into keywording structures for archiving this material. Hence, our ability to accurately communicate our findings about these methods to others through journal articles, databases, or more recently, websites, is severely hampered.
Historically, development of in vitro and other alternative methods to animal testing has relied heavily upon the disciplines of toxicology, pharmacology, biochemistry, immunology, physiology, and genetics. As a result, the descriptive nomenclature of this field is a diverse collection of words derived from multiple sources. And most public and private databases of information about alternatives to animal testing have been indexed by different systems. So, in addition to the fact that the words used as descriptors for the same concept may not be the same, the concepts chosen as the basis for indexing strategies may also differ.
In an effort to clarify and resolve some of this ambiguity, the European Center for Validation of Animal Methods recently sponsored a workshop for information providers in which a decision was made to construct a thesaurus of terms for use in describing alternatives to animal testing (4). This event marks the first organized attempt to develop a well-defined nomenclature for research methods that do not use animals. What is also needed is more common use of these words as indexing terms.
With the advent of the information age, many new methods of information storage, retrieval, and dissemination are currently in use or under development. Keywords (descriptors) remain a very prevalent form of indexing. Authors submitting manuscripts to many major scientific journals are typically requested to furnish from 3 to 10 keywords describing the research they wish to publish. These keywords are then used to index the article in the publisher's archives. Larger databases of information (e.g., MEDLINE or TOXLINE) may also index the article. But, they may choose to index the article by an entirely different set of keywords depending upon the keywording strategy they employ.
In view of the prevalence, in the area of alternatives to animal testing, of research involving methods development, keywords describing methods would seem an integral part of any keywording structure used to index the results from this research. Many indexing strategies, however, do not emphasize the incorporation of terms describing methods. The National Library of Medicine, which operates MEDLINE and TOXLINE, considers terms describing methods as part of a secondary, not primary, tier of concepts to be indexed (5). Many, if not most, scientific journals requesting keywords from authors do not specify which concepts are to be keyworded.
Recently, a keywording scheme which incorporates words describing methods for articles about alternatives to animal testing was proposed (6). The strategy, itself, is relatively simple, incorporating words for toxic insult studied, method used, and endpoint measured.
Toxic insult studied is defined in a classic toxicological sense. With regard to alternatives to skin irritation testing, examples of keywords are irritation, corrosion, and phototoxicity.
Method used refers to the assay used to measure result. Examples include agarose diffusion assay, chorioallantoic membrane assay, Eytex assay,and kenacid blue assay.
Endpoint measured refers to actual process/activity measured. General cellular processes such as cell adherence, cell division, and protein synthesis can be included as well as more specific measures such as acid phosphatase activity, arachidonic acid release, and prostaglandin E2 activity.
An example of application of this keywording strategy to a journal article is as follows.
Development of in vitro methods for use of human skin cell cultures for skin and eye irritancy assessments of aqueous incompatible materials. Mary A. Perkins, Deirdre A. Roberts, and Rosemarie Osborne. Human & Environmental Safety Division, The Procter & Gamble Company, Cincinnati, Ohio.
In order to address the pressing need to reduce or replace the use of rabbits for prediction of human skin and eye irritancy potential, cultured human skin cells were evaluated. Currently available submerged cultures have limitations due to the aqueous buffered medium used for test material dilution. We have previously shown that these models are limited in their ability to predict irritancy potential for aqueous incompatible materials, product formulations and acids/bases. To overcome these limitations, we developed a unique protocol utilizing Marrow-Tech Skin2 cultures for topical application of aqueous incompatible test materials as an alternative model for skin and eye irritancy testing. Methods were developed for topical application of and removal of neat test materials as an alternative model for skin and eye irritancy testing. Methods were developed for topical application of and removal of neat test materials for acute damage evaluations. Materials tested in this model included a wide array of product formulation types, including liquids, gels, creams, foams, pastes, solids, powders and granulars. A battery of endpoints (MTT cell viability assay, lactate dehydrogenase enzyme release, and inflammatory mediator-PGE2 release) were measured, representing final common pathways of skin or eye response to diverse test materials. Preliminary results indicate that, with this unique protocol, in vitro skin or eye irritancy assessments correlate well with the in vivo irritancy of these materials (7).
Keywords: Irritation/Skin/MTT/Lactate Dehydrogenase/PGE2
This simple keywording strategy was applied to a small collection of articles describing alternatives to skin irritation testing in animals. The words thus collected were compared to the current medical subject headings (MeSH) of the National Library of Medicine (NLM) (see "Keywords for Alternatives to Skin Irritation Testing and Related MeSH" at end of article). Many of the keywords about skin irritation alternatives collected by this project have comparable, if not exact, matching terms in MeSH. There are words that are not matched in the MeSH. This doesn't mean that NLM databases can't be searched using all the keywords collected by this project. What should be considered is that use of the MeSH to find keywords describing methods about alternatives to skin irritation testing in animals may not prove fruitful in some instances (for example, words describing models--Skin, Emerged Dermal Equivalent, ZK1000).
The bibliographic database that served as the source of keywords for this project was composed of 94 records of abstracts obtained from articles published in the following scientific journals.
Abstracts from these journals were indexed using Pro-Cite bibliographic software (Research Information Systems, Carlsbad, CA). Data were entered into numerous fields (for example, author name, title of article, journal name, abstract, and keywords). "Authority" lists were generated containing frequently used citation elements such as journal abbreviations or keywords. These lists were then consulted during data entry. Although, this work might be considered limited because only 94 abstracts were surveyed, the keywords collected represent a good sample of the nomenclature in use. And it is a good example of how effectively the keywording strategy described can be used to collect words pertinent to alternative methods for animal testing.
Keywording an article can provide useful information to people searching for alternatives. Retrieval of an article describing an alternative method to animal experimentation can be greatly enhanced by using well-defined keywords which describe the basic components of the study such as toxic insult studied, method used, endpoint measured.
This suggested keywording scheme is not meant to replace indexing strategies already in place but simply to augment those structures with elements describing methodology. Just as changes in shading and color often add depth to an artistic rendering, additional keywords can add valuable descriptive detail to the basic framework of words chosen.
In summary, both better definition of the nomenclature used to describe alternative methods to animal testing and more frequent use of these words as keywords will enhance our ability to store, retrieve, and disseminate information about these new research techniques.
Note: Dr. Huggins would like to thank David Anderson and Krys Bottrill for their helpful suggestions regarding this work. She can be reached by phone: (609) 462-8159, fax (609) 716-8030, or e-mail: email@example.com for further information.
|Agarose Diffusion Assay||Gel Diffusion Tests|
|Alcian Blue Assay||Alcian Blue|
|Aniline Blue Assay||Aniline Blue|
|Cell Count||Cell Count|
|Chorioallantoic Membrane Assay||**|
|3T3 Mouse Embryo Fibroblasts||3T3 cells|
|C3H Mouse Embryo Fibroblasts||Mice, inbred C3H|
|HaCAT Spontaneously Immortalized Human Keratinocyte Cell Line||**|
|L929 Mouse Fibroblasts Cells||**|
|Methyl Cellulose Culture||Methylcellulose+|
|Normal Human Epidermal Keratinocyte||**|
|Human||Human [all clinical and experimental studies]|
|Rat||Rats, inbred strains+|
|Hair Follicle||Epidermis+, hair follicle|
|Sublingual Mucosa||Sublingual Region|
|Organ Culture||Organ Culture|
|Emerged Dermal Equivalent||**|
|Isolated Perfused Pig Skin Flap||**|
|Living Dermal Equivalent||**|
|Living Dermal Model-Mast Cell||**|
|Living Skin Equivalent||**|
|Carboxyfluroescein Diacetate Acetoxymethyl Ester||Fluoresceins|
|Fluorescein Diacetate||Fluorescein Diacetate|
|Cell Adherence||Cell Adhesion|
|Cell Division||Cell Division|
|Cytotoxicity||Cytotoxicity; Cytotoxicity tests, immunologic+|
|12-Hydroxyeicosatetranoic acid||Hydroxyeicosatetranoic acids|
Note: General MeSH terms which may be helpful are "skin substitutes" or "artificial skin".
** Keywords for which exact or closely related terms in MeSH were not found.
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