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Comparison of murine models for the identification of potential chemical sensitizers.

Howell-MD; Manetz-TS; Meade-BJ
Toxicologist 1999 Mar; 48(1-S):314
Efforts have been underway to develop a phenotypic analysis assay for the identification and differentiation of chemicals with the potential to induce irritation and IgE mediated and T cell mediated sensitization. The purpose of these studies was to compare results obtained with this assay to those obtained in the Mouse Ear Swelling Test (MEST) and the Local Lymph Node Assay (LLNA). The Irritancy/Phenotypic analysis assay utilizes the endpoints of ear swelling for irritation and the expression of B220 and IgE on the lymph node cells draining the site of chemical exposure as an indicator of sensitization. By measuring the increase in ear swelling, the MEST evaluates' the elicitation response of previously sensitized mice following chemical challenge. A mouse ear swelling irritancy assay is used to determine the minimal irritating concentration of each chemical to be used as the challenge concentration in the MEST. The LLNA utilizes [3H]-thymidine incorporation into draining lymph node cells as a measure of lymphocyte proliferation during the sensitization phase. Known human sensitizers, potassium dichromate (PDC) and 2,4-dinitrocholobenzene (DNCB), and the irritant methyl salicylate (MSC) were used for the dose response comparison studies. Female BALB/c mice were exposed topically to the chemicals following the protocol for each assay (four consecutive daily exposures for both the irritancy/phenotypic analysis and LLNA and three days of induction followed by a single challenge eight days post initial exposure for the MEST). DNCB was identified as a sensitizer in all three assays at concentrations as low as 0.25%. MSC tested negative at all concentrations in the MEST, LLNA, and phenotypic analysis assay. PDC tested positive as a sensitizer in the LLNA at concentrations as tow as 0.25%, while it tested positive only at the 0.5% concentration at the 48 hr measurement of the MEST. Results' obtained in these studies from the Irritancy/Phenotypic analysis assay were comparable to those for the MEST and LLNA.
Irritants; Ear-disorders; Ears; Animal-studies; Laboratory-animals; Statistical-analysis; Analytical-methods; Analytical-chemistry; Sensitization; Sensitivity-testing; Lymph-nodes
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The Toxicologist. Society of Toxicology 38th Annual Meeting, March 14-18, 1999, New Orleans, Louisiana