Structure activity relationships in skin sensitization using the murine local lymph node assay. 1995

J Ashby, and D A Basketter, and D Paton, and I Kimber
Zeneca Central Toxicology Laboratory, Alderley Park, Macclesfield, Cheshire, UK.

Murine local lymph assay node data for 106 chemicals are listed. Among these, 73 are active in the assay indicating their potential as skin sensitizing agents. Broad structure activity relationships (SAR) are suggested based on the electrophilic theory of skin sensitization suggested by Landsteiner and Jacobs in 1936, and elaborated by Dupuis and Benezra in 1982. Eight classes of agent are discerned; electrophiles, potential electrophiles after metabolism, Michael-reactive agents, benzoylating agents, ionic chemicals and miscellaneous agents. The electrophilic theory cannot at present fully explain the activity of agents in the last two classes. That fact will hopefully focus research into their mode of action. Some chemicals fit equally into more than one class, and such agents are entered into the several classes in order not to bias the analysis. Attention is given to why not all chemicals of a class are active in the assay. It is concluded that a combination of inappropriate lipophilicity, molecular size and metabolic detoxification are responsible for these inactivities. Given a sufficient number of analogues tested within each class it should be possible eventually to predict with accuracy the skin sensitizing potential of new members of the class. However, the present analysis is qualitative, not quantitative. Finally, the parallelism between sensitizing potential and mutagenic potential for chemicals is explored further.

UI MeSH Term Description Entries
D007159 Immunologic Tests Immunologic techniques involved in diagnosis. Diagnosis, Immunological,Immunodiagnosis,Diagnosis, Immunologic,Immunologic Diagnosis,Immunologic Test,Immunological Tests,Tests, Immunologic,Diagnoses, Immunologic,Diagnoses, Immunological,Immunodiagnoses,Immunologic Diagnoses,Immunological Diagnoses,Immunological Diagnosis,Immunological Test,Test, Immunologic,Test, Immunological,Tests, Immunological
D008198 Lymph Nodes They are oval or bean shaped bodies (1 - 30 mm in diameter) located along the lymphatic system. Lymph Node,Node, Lymph,Nodes, Lymph
D000485 Allergens Antigen-type substances that produce immediate hypersensitivity (HYPERSENSITIVITY, IMMEDIATE). Allergen
D000818 Animals Unicellular or multicellular, heterotrophic organisms, that have sensation and the power of voluntary movement. Under the older five kingdom paradigm, Animalia was one of the kingdoms. Under the modern three domain model, Animalia represents one of the many groups in the domain EUKARYOTA. Animal,Metazoa,Animalia
D012867 Skin The outer covering of the body that protects it from the environment. It is composed of the DERMIS and the EPIDERMIS.
D013329 Structure-Activity Relationship The relationship between the chemical structure of a compound and its biological or pharmacological activity. Compounds are often classed together because they have structural characteristics in common including shape, size, stereochemical arrangement, and distribution of functional groups. Relationship, Structure-Activity,Relationships, Structure-Activity,Structure Activity Relationship,Structure-Activity Relationships
D017449 Dermatitis, Allergic Contact A contact dermatitis due to allergic sensitization to various substances. These substances subsequently produce inflammatory reactions in the skin of those who have acquired hypersensitivity to them as a result of prior exposure. Allergic Contact Dermatitis,Dermatitis, Allergic Eczematous,Dermatitis, Contact, Allergic,Allergic Contact Dermatitides,Allergic Eczematous Dermatitides,Allergic Eczematous Dermatitis,Contact Dermatitides, Allergic,Contact Dermatitis, Allergic,Dermatitides, Allergic Contact,Dermatitides, Allergic Eczematous,Eczematous Dermatitides, Allergic,Eczematous Dermatitis, Allergic
D051379 Mice The common name for the genus Mus. Mice, House,Mus,Mus musculus,Mice, Laboratory,Mouse,Mouse, House,Mouse, Laboratory,Mouse, Swiss,Mus domesticus,Mus musculus domesticus,Swiss Mice,House Mice,House Mouse,Laboratory Mice,Laboratory Mouse,Mice, Swiss,Swiss Mouse,domesticus, Mus musculus

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