Comparison of murine assays for the identification of chemical sensitizers

Citation
Md. Howell et al., Comparison of murine assays for the identification of chemical sensitizers, TOX METHOD, 10(1), 2000, pp. 1-15
Citations number
31
Categorie Soggetti
Pharmacology & Toxicology
Journal title
TOXICOLOGY METHODS
ISSN journal
10517235 → ACNP
Volume
10
Issue
1
Year of publication
2000
Pages
1 - 15
Database
ISI
SICI code
1051-7235(200001/03)10:1<1:COMAFT>2.0.ZU;2-I
Abstract
Efforts are under way, to develop a phenotypic analysis assay capable of id entifying and differentiating chemicals with the potential to induce irrita tion and IgE-mediated and T-cell-mediated sensitization. These studies comp are results obtained with the irritancy/phenotypic analysis assay to those obtained in, the mouse ear-swelling test (MEST) and the local lymph node as say (LLNA). Female BALB/c mice (5 animals per group) were exposed topically to the human sensitizers 2,4-dinitrochlorobenzene (DNCB) anal potassium di chromate (PDC) as well as the irritant methyl salicylate (MSC), following t he protocol for each assay. DNCB was identified as a sensitizer in the LLNA and phenotypic analysis assay at concentrations as low 0.25%. In the MEST DNCB was considered positive in concentrations as lour as 0.01 and 0.05% at the 24- and 48-h measurements of the MEST respectively. PDC tested positiv e as a sensitizer in the LLNA and the phenotypic analysis assay at concentr ations as low as 0.25 and 0.1%, respectively. In the MEST, PDC was negative at the 24-h time point and tested positive only at the 48-h measurement at the highest concentration tested, 0.5%. Both DNCB and PDC induced an eleva tion in total serum IgE at the 0.5% concentrations. MSC was negative for se nsitizing potential at all concentrations tested in all four assays. Phenot ypic analysis of lymph node cells removed from animals dosed with the three chemicals gave results similar to the LLNA, but had the advantage of detec ting chemicals with the capacity to induce an increase in the IgE(+) cell p opulation.