EVALUATION OF AURICULAR LYMPH-NODE CELL-PROLIFERATION IN ISOTHIAZOLONE-TREATED MICE

Chemicals that bind to protein may cause immunological responses that include allergic contact hypersensitivity mediated by T cells. Various animal models have been used to predict chemical-mediated contact sen sitization. One assay that has recently been developed utilizes the pr oliferation response induced in the draining auricular lymph node afte r exposure to contact sensitizers, This assay has been modified to a s impler method that results in the more rapid processing of samples wit h greater reproducibility, Isothiazolones are chemicals used as biocid es in various applications which at greater than use concentrations ma y cause allergic contact hypersensitivity. The mouse auricular lymph n ode cell proliferation assay has been used to examine the potential of various isothiazolones to induce contact sensitization, The extent of lymph node cell proliferation was dependent on the concentration of i sothiazolone, the vehicle used in the application, and the ability of isothiazolone to bind to protein. Kathon biocide contains two isothiaz olones: 5-chloro-2-methyl-4-isothiazolin-3-one (CMI)(2) and 2-methyl-4 -isothiazolin-3-one (MI). In vivo studies have shown that protein bind ing correlates with auricular lymph node cell proliferation and an inc rease in auricular lymph node size, CMI, which binds to protein, induc ed an auricular lymph node cell proliferation response while MI, which poorly binds to protein, neither stimulated a proliferative response nor induced an increase in lymph node size at concentrations similar t o CMI. In other studies that compared the auricular lymph node cell pr oliferation of four different isothiazolones, it was shown that dramat ically different proliferation responses were observed and that these responses were positively correlated with contact sensitization in the guinea pig. (C) 1995 Society of Toxicology.