{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,10,16]],"date-time":"2025-10-16T00:41:31Z","timestamp":1760575291925,"version":"build-2065373602"},"reference-count":32,"publisher":"Wiley","issue":"4","license":[{"start":{"date-parts":[[2006,5,17]],"date-time":"2006-05-17T00:00:00Z","timestamp":1147824000000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["J of Applied Toxicology"],"published-print":{"date-parts":[[2006,7]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:p>The local lymph node assay (LLNA) is used to assess the skin sensitization potential of chemicals. In the standard assay, mice are treated topically on the dorsum of both ears with test substance for 3 days. Following 2 days of rest, the initiation of the hypersensitivity response is evaluated by injecting <jats:sup>3<\/jats:sup>H\u2010thymidine into a tail vein, and then measuring the levels of radioisotope incorporated into the DNA of lymph node cells draining the ears. In the current study, BALB\/c mice were treated with the contact sensitizers hexylcinnamic aldehyde (HCA) and oxazolone, and the nonsensitizer methyl salicylate. The proliferative response of lymph node cells was evaluated in an <jats:italic>ex vivo<\/jats:italic> assay, in which isolated cells were cultured <jats:italic>in vitro<\/jats:italic> with <jats:sup>3<\/jats:sup>H\u2010thymidine. Treatment of mice with HCA at 5\u201350% resulted in concentration\u2010related increases in <jats:sup>3<\/jats:sup>H\u2010thymidine incorporation, with stimulation indices ranging from 3 to 14. Low animal\u2010to\u2010animal variability was seen in three replicate assays testing HCA at 25%. As anticipated, the proliferative response induced by the potent sensitizer oxazolone at 0.25% was greater than HCA at all concentrations tested. Stimulation indices of 1.5 and 3 were seen in two independent experiments with methyl salicylate. These equivocal findings were likely due to the irritancy properties of the compound. Importantly, measuring <jats:italic>ex vivo<\/jats:italic> <jats:sup>3<\/jats:sup>H\u2010thymidine incorporation was more sensitive than evaluating lymph node weight and cellularity, and <jats:italic>in vitro<\/jats:italic> bromodeoxyuridine incorporation. Furthermore, the results of the <jats:italic>ex vivo<\/jats:italic> LLNA were comparable to the standard assay. This study provided evidence that supports the use of an <jats:italic>ex vivo<\/jats:italic> LLNA for hazard assessment of contact hypersensitivity. 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