Examination of the Local Lymph Node Assay for Use in Contact Sensitization Risk Assessment

Gerberick, G. Frank; House, Robert V.; Fletcher, E. Robert; Ryan, Cindy A.

doi:10.1093/toxsci/19.3.438

Cited by 13 publications

(17 citation statements)

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“…Basketter (2003); Gerberick et al (1992); Hilton et al (1998); Sailstad et al (1995) 1073 Marzulli and Maibach (1974) Glyoxal (107- (2003); Basketter et al (1994Basketter et al ( , 2001b; Basketter and Kimber (2001); Basketter and Scholes (1992); Montelius et al (1994) 3937 4311 Jordan and King (1977); Ford et al (1988); Marzulli and Maibach (1980); Steltenkamp et al (1980b) Imidazolidinyl urea (39236-46-9) 6952 Basketter (2003); Basketter and Scholes (1992) 3846 Jordan and King (1977) Isoeugenol (97-54-1) 524 Basketter (2003); Basketter and Kimber (2001); Basketter and Scholes (1992); Kimber and Weisenberger (1991); Loveless et al (1996); Wright et al (2001) 657 Marzulli and Maibach (1980); Thompson et al (1983) Kanamycin (59-01-8) 2075…”

Section: Discussionmentioning

confidence: 99%

Quantitative relationship between the local lymph node assay and human skin sensitization assays

Schneider

Akkan

2004

Regulatory Toxicology and Pharmacology

104

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Section: Discussionmentioning

confidence: 99%

Quantitative relationship between the local lymph node assay and human skin sensitization assays

Schneider

Akkan

2004

Regulatory Toxicology and Pharmacology

104

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“…However, we believe that the in situ LLNA method has disadvantages in terms of the technical difficulty of 3HTdR injection and the necessary killing of animals contaminated by radioisotope. In this study, we proposed a new parameter, Sltotal, for evaluation of contact (Kimber et al 1990a;Ikarashi et al 1992Ikarashi et al , 1993b, abrasion of the skin (Robinson and Sneller 1990;Ikarashi et al 1992) and increasing number of applications Gerberick et al 1992) have been adopted. However, these modifications produced only a limited increase in test sensitivity.…”

Section: Discussionmentioning

confidence: 99%

A sensitive mouse lymph node assay with two application phases for detection of contact allergens

1993

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A predictive test using mice for the identification of contact sensitizing chemicals was developed. Contact sensitizing activity is measured as a function of draining lymph node activation following application of test chemical. Experimental conditions for assessment of induced lymph node cell (LNC) responses have been optimized. BALB/c mice were initially treated with intradermal injections of test chemical in Freund's complete adjuvant emulsion. Five days after intradermal injection, mice were exposed topically to chemical in vehicle on the ears daily for 3 consecutive days. Next day following the final exposure, changes in lymph node weight, total cell number in the draining lymph nodes and LNC proliferation for 24 h culture were assessed. The performance of the method was evaluated with ten sensitizing chemicals and a non-sensitizing irritant, sodium lauryl sulfate (SLS). The LNC proliferation induced by combination of intradermal injection and topical application of sensitizing chemicals was more clearly increased than that following only topical application. With the single exception of sulfanilic acid, the method developed was able to detect the sensitizing capacity of chemicals that failed to induce sensitization in the local lymph node assay. Under the conditions used, SLS did not induce measurable lymph node responses. These results suggest that the mouse lymph node assay can provide a sensitive screening test for weak to moderate sensitizers. In addition, the assay offers the advantages of objective and quantitative endpoints, and is suitable for the evaluation of colored or irritant chemicals.

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“…Predictive testing of small chemicals for the capacity to evoke allergic contact dermatitis is routinely performed by use o f established animal sensitization models like the gui nea pig maximization test [1] and the murine local lymph node assay [2], Regulations o f the European Community and the public opinion demand the development of alterna tive in vitro methods for this purpose. Aim of this study was to work out and evaluate an in vitro method suitable to meet these criteria.…”

Section: Introductionmentioning

confidence: 99%

An Approach to Predictive Testing of Contact Sensitizers in vitro by Monitoring Their Influence on Endocytotic Mechanisms

Lempertz¹,

Kühn²,

Knop³

et al. 1996

Int Arch Allergy Immunol

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Endocytotic activation of epidermal Langerhans cells (LC) by immunogenic haptens is an early event during development of allergic contact dermatitis. In this work a fast and objective flow-cytometric assay for predictive in vitro testing of contact sensitizers by monitoring their influence on endocytotic mechanisms in murine LC was developed. Epidermal cell suspensions were labelled with a monoclonal antibody directed to MHC class II molecules and pH-sensitive fluorochrome-coupled second-step reagents. For untreated LC a significant quenching of fluorescence intensity by internalization of the MHC-antibody complexes into acidic compartments was noticed. Similar results were obtained in the presence of irritants, the lectin concanavalin A and the phorbol ester phorbol 12-myristate 13-acetate. In contrast stimulation with several well-defined sensitizing compounds resulted in partial conservation of the fluorescence intensity due to the internalization of the labelled complexes into less acidic compartments. Monitoring this modulation of endocytosis is an effective in vitro method to test for properties typical for moderate and strong contact sensitizers. It will help to assess the risk of unknown chemicals to act as haptens and should be useful for restriction of animal experimentation in this field.

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Examination of the Local Lymph Node Assay for Use in Contact Sensitization Risk Assessment

Cited by 13 publications

References 0 publications

Quantitative relationship between the local lymph node assay and human skin sensitization assays

Quantitative relationship between the local lymph node assay and human skin sensitization assays

A sensitive mouse lymph node assay with two application phases for detection of contact allergens

An Approach to Predictive Testing of Contact Sensitizers in vitro by Monitoring Their Influence on Endocytotic Mechanisms

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