An Integrated Model for the Differentiation of Chemical-Induced Allergic and Irritant Skin Reactions

Homey, Bernhard; Schilling, Christiane von; Blümel, Jörg; Schuppe, Hans‐Christian; Ruzicka, Thomas; Ahr, H J; Lehmann, Percy; Vohr, Hans-Werner

doi:10.1006/taap.1998.8535

Cited by 60 publications

(37 citation statements)

References 48 publications

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“…In our study, since DI showed values > 1 for all concentrations tested, DNCB is an allergic compound, as supported by the results of FCM analysis, i.e., increases in B220+/I-A+ cells (B cell) and CD69+/I-A+ cells (activated B cell) were observed (Table 5). Homey et al (1998) reported that the most prominent differences between irritant and allergic reactions were seen for the expression of CD69+/I-A+ lymph node cells. Allergen (oxazolone) treatment dramatically upregulated CD69 on I-A+ lymph node cells.…”

Section: Discussionmentioning

confidence: 99%

“…FCM analysis was performed using FACScan equipment (Becton Dickinson). To differentiate between allergic and irritant potential, Differentiation Indices (DI) were calculated, as described (Homey et al, 1998), using the following formulas. This method was carried out in Laboratory H.…”

Section: Integrated Model For Differentiating Skin Reaction (Imds)mentioning

confidence: 99%

“…Hariya et al (1999) reported that IL-2 production with lymph node weight and CD4 positive subset ratio in LNC improved sensitivity. Homey et al (1998) and Vohr et al (2000) presented an integrated model for differentiating skin reaction (IMDS), which assesses ear swelling and cell proliferation in lymph nodes.…”

Section: Introductionmentioning

confidence: 99%

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Local lymph node assay with non-radioisotope alternative endpoints.

et al. 2002

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-The local lymph node assay has recently been accepted by regulatory agencies as a standalone alternate method for predicting allergic contact dermatitis. To compare the sensitivity of non-radioisotope methods with that of the standard assay, we determined if these modified methods would affect evaluation of sensitization potency. For this reason, we used 2,4-dinitrochlorobenzene (DNCB) and benzocaine for different sensitizing criteria.Female CBA mice were treated for 3 days with a test compound or vehicle applied to each side of both ears. Bilateral auricular lymph node proliferative activity was assessed by the following endpoints with incorporation of 3 H-methyl thymidine (3H-TdR), bromodeoxyuridine (BrdU) in vivo, and BrdU ex vivo, IL-2 production, and proliferating cell nuclear antigen (PCNA) expression. Ear thickness was also tested.The strong sensitizer DNCB was detectable by any of the non-radioisotope endpoints as well as by radioisotope-dependent standard assay. On the other hand, when evaluating the weak sensitizer benzocaine, significant changes were evident in BrdU incorporation ex vivo and in vivo, and IL-2 production. We believe that these non-radioisotope methods can assess allergic contact dermatitis caused by chemicals even in the laboratory, where it can be difficult to handle radioisotopes.

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Section: Discussionmentioning

confidence: 99%

Section: Integrated Model For Differentiating Skin Reaction (Imds)mentioning

confidence: 99%

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Local lymph node assay with non-radioisotope alternative endpoints.

et al. 2002

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“…Unfortunately, again, this trend was not apparent for the other two endpoints outlined in the Table 1. A DI was defined describing the relation between skin-draining lymph node cell activation (lymph node cell count index) and skin inflammation (ear swelling). A DI > 1 indicates an allergic reaction pattern, whereas a DI < 1 demonstrates an irritant potential of a chemical (Homey et al, 1998). As the differentiation indices were found to be > 1 in our study, the applied concentrations of DNCB were deemed to have caused only an allergic effect, and not any irritant effect.…”

Section: Lymph Node-related Parameters and Ear Thickening Outcomesmentioning

confidence: 49%

“…Nevertheless, the fact that the in vivo method cytokine studies used cells that had 'seen' BrdU while those in the ex vivo method never 'saw' the agent (and therefore did not become functionally modified it) might be an additional critical factor that works in the favor of the use of the ex vivo BrdU method to assess 'truer' measures of function of lymphocytes from hosts being used to assess a potential for ACD caused by a test chemical. Homey et al (1998) and Vohr et al (2000) presented an integrated model for differentiating skin (IMDS) reaction that assessed ear swelling and cell proliferation in lymph nodes to detect and differentiate chemical-induced irritant and allergic skin responses. In our study, since DI values were > 1 for all concentrations, DNCB is an allergic compound.…”

Section: Discussionmentioning

confidence: 99%

Evaluation of auricular lymph node cell lymphocyte proliferation and cytokine production as non-radioactive endpoints during murine contact allergy

Ülker

Atak

Ateş

et al. 2011

Journal of Immunotoxicology

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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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An Integrated Model for the Differentiation of Chemical-Induced Allergic and Irritant Skin Reactions

Cited by 60 publications

References 48 publications

Local lymph node assay with non-radioisotope alternative endpoints.

Local lymph node assay with non-radioisotope alternative endpoints.

Evaluation of auricular lymph node cell lymphocyte proliferation and cytokine production as non-radioactive endpoints during murine contact allergy

Local lymph node assay: use in hazard and risk assessment

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