Murine Model for Contact Sensitization

Rodenberger, Sharon L.; Ledger, Philip W.; Prevo, Mary E.

doi:10.3109/15376519309044573

Cited by 5 publications

(2 citation statements)

References 11 publications

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“…33 Furthermore, it must be appreciated that the majority of non-sensitizing skin irritants fail to elicit positive responses in the LLNA. 6,12,33,[34][35][36] Another issue that is raised sometimes is the performance of the LLNA with metal allergens, and in particular nickel salts. Nickel is a common cause of allergic contact dermatitis and nickel salts are positive in the guinea pig maximization test.…”

Section: Interpretation Of Llna Datamentioning

confidence: 99%

“…Included among these are the use of an alternative isotope, changes to the duration of exposure and/or the analysis of lymph nodes isolated from individual mice (rather than pooled for each experimental group). 34,36,[50][51][52] Results deriving from recent international inter-laboratory evaluation and validation studies of the LLNA indicate that the method is sufficiently robust to accommodate conservative procedural modifications such as these without loss of performance or variation in the data obtained. [12][13][14][15][16] Some attempts have been made to develop supplementary or alternative endpoints for the LLNA that it is claimed might permit a more exacting discrimination between contact allergens and skin irritants.…”

Section: Procedural Modifications Alternative Endpoints and Related mentioning

confidence: 99%

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Local lymph node assay: use in hazard and risk assessment

1999

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The murine local lymph node assay (LLNA) was developed as an alternative method for the identification of chemicals that have the ability to cause skin sensitization and allergic contact dermatitis. The assay now has been evaluated extensively in the context of both national and international inter‐laboratory collaborative trials and has been the subject of detailed comparisons with guinea pig test methods and human skin sensitization data. On the basis of these evaluations the LLNA has been endorsed recently by the US Interagency Coordinating Committee on the Validation of Alternative Methods (ICCVAM) as a stand‐alone method for skin sensitization testing. The assay offers a number of important benefits compared with conventional guinea pig test methods, among these being provision of an objective and quantitative endpoint. Moreover, the LLNA provides advantages in the context of animal welfare; compared with guinea pig tests, fewer animals are required and these animals are subject to less trauma. It is important now that the validation status of the LLNA is recognized and the method applied widely so that these advantages may be realized. Hazard identification represents only the first step in the risk assessment process. A full toxicological evaluation of skin sensitization activity requires an understanding of relative potency. Guinea pig methods do not lend themselves readily to assessment of potency, and interest recently has focused on the utility of the LLNA for this purpose. Contained within this review article are brief descriptions of the history of the LLNA and the immunobiological basis for the method, together with detailed accounts of the conduct and interpretation of the assay. Procedural modifications to, and alternative endpoints for, the LLNA are considered also. Finally, the current regulatory status of the LLNA is summarized and the application of the method for the purposes of defining relative potency and developing risk assessments is reviewed. Copyright © 1999 John Wiley & Sons, Ltd.

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Section: Interpretation Of Llna Datamentioning

confidence: 99%

Section: Procedural Modifications Alternative Endpoints and Related mentioning

confidence: 99%

Local lymph node assay: use in hazard and risk assessment

1999

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Evaluation of lymphocyte proliferation by immunohistochemistry in the local lymph node assay

Boussiquet-Leroux

Durand-Cavagna

Herlin

et al. 1995

J of Applied Toxicology

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A modified version of the local lymph node assay (LLNA) is presented, using bromodeoxyuridine to label proliferating lymphocytes. Cell counting is done on mid-sagittal sections of individual nodes under light microscopy. Two irritants (sodium lauryl sulfate and salicylic acid), four allergens of various sensitizing potential (potassium dichromate, 4-chloroaniline, neomycin sulfate and nickel sulfate) and one chemical of unknown sensitizing potential (ethyl 3-aminobenzoate) were tested either in the short protocol using three daily topical applications and/or in the long protocol with a pre-exposure step under an occluded patch. A weak T cell proliferation was noted with both irritants in the short protocol, but not in the long protocol. Potassium dichromate induced a strong proliferative response in the short protocol. A lesser sensitizing potential was detected for 4-chloroaniline, ethyl 3-aminobenzoate and neomycin sulfate but only in the long protocol. Nickel sulfate was negative in both protocols. The long protocol was the most valuable for weak or moderate sensitizers. Histological examination of nodes ruled out intercurrent processes. The present procedure offers several advantages. The use of a non-isotopic marker enables this test to be run in a routine safety assessment department and allows the preparation of permanent slides. An increased specificity is obtained by restricting cell counting to the paracortex. Moreover, the collection of individual data permits statistical analysis of the results. This method is sensitive and reproducible and may be viewed as a useful adjunct to the LLNA.

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