title: Investigation of the sensitising and cross-sensitising potential of textile dyes and beta-lactam antibiotics using a biphasic mice local lymph node assay.
abstract: We used a modified protocol of the murine local lymph node assay (LLNA) to study the cross-sensitising potential of (a) textile dye disperse yellow 3 and its metabolite 2-amino-p-cresol, (b) two antibiotics, penicillin G and cefotiam. The test substances were applied in a biphasic manner, i.e. first on the shaved skin of the back followed by application on the dorsal side of the ears after 2 weeks. The end-points analysed included thickness and weight of an ear-biopsy, weight and cell number of the draining lymph node, and lymphocyte cell surface markers analysed by flow-cytometry. Disperse yellow 3 and its metabolite significantly altered the various end-points at both the tested concentrations (0.5 and 1%), thus demonstrating the sensitising potential of the two substances. The cross-sensitisation study showed significant modulation in the tested variables in the treated group as compared to the control, signifying cross-sensitisation potential of the two substances. Penicillin G and cefotiam showed significant changes in various end-points, pointing towards their sensitising potential. However, even at 50% concentration of the beta-lactams no significant change in any end-point indicating absence of cross-reactivity of the antibiotics was noticed. We conclude that a biphasic, modified protocol of the LLNA is a suitable approach to test for a cross-reactivity potential of two related compounds.
authors.affiliation: Department of Toxicology, Institute of Clinical Pharmacology and Toxicology, Charité Medical University, Campus Benjamin Franklin, Berlin, Germany.
authors.forename: Varun
authors.initials: V
authors.lastname: Ahuja
authors.forename: Clemens
authors.initials: C
authors.lastname: Schreiber
authors.forename: Thomas
authors.initials: T
authors.lastname: Platzek
authors.forename: Ralf
authors.initials: R
authors.lastname: Stahlmann
mesh_terms: D000485:Allergens / Q000378:metabolism / Q000633:toxicity*; D000818:Animals; D000900:Anti-Bacterial Agents / Q000633:toxicity*; D001391:Azo Compounds / Q000378:metabolism / Q000633:toxicity; D001402:B-Lymphocytes / Q000187:drug effects; D015415:Biomarkers / Q000032:analysis; D004396:Coloring Agents / Q000378:metabolism / Q000633:toxicity*; D003408:Cresols / Q000633:toxicity; D003429:Cross Reactions; D004305:Dose-Response Relationship, Drug; D005260:Female; D023441:Local Lymph Node Assay; D051379:Mice; D008807:Mice, Inbred BALB C; D012867:Skin / Q000187:drug effects / Q000378:metabolism; D013601:T-Lymphocytes / Q000187:drug effects; D013784:Textiles; D047090:beta-Lactams / Q000633:toxicity*
chemical_list: D000485:Allergens; D000900:Anti-Bacterial Agents; D001391:Azo Compounds; D015415:Biomarkers; D004396:Coloring Agents; D003408:Cresols; D047090:beta-Lactams; C024957:Dispersion Yellow 3