Dw. Potter et Ga. Hazelton, EVALUATION OF AURICULAR LYMPH-NODE CELL-PROLIFERATION IN ISOTHIAZOLONE-TREATED MICE, Fundamental and applied toxicology, 24(2), 1995, pp. 165-172
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.