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Title: Is there cross-reactivity between toluene diamine (TDA) and toluene diisocyanate (TDI)?
Authors: De Vooght, Vanessa
Vanoirbeek, Jeroen
Synhaeve, Nicholas
Nemery, Benoit
Hoet, Peter #
Issue Date: 2008
Conference: BelTox Annual Meeting location:Brussels, Belgium date:28 November 2008
Abstract: Introduction: Toluene diamine (TDA) is formed when toluene diisocyanate (TDI), a potent sensitizer, comes in contact with aqueous environment. The sensitizing capacity of TDA and the cross-reactivity between TDI and TDA are unknown.
Methods: TDA (5-25%) and TDI (0.3%), dissolved in acetone/olive oil (AOO) (4:1) were tested in the mouse local lymph node assay (LLNA). To determine the respiratory sensitizing capacity of TDA and the cross-reaction with TDI, a mouse model of chemical-induced asthma was used. On day 1 and 8, BALB/C mice were dermal sensitized with TDI (0.3%), TDA (20%) or AOO (4:1) (20 µl/ear). On day 15, they received an intranasal instillation of TDI (0.1%), TDA (0.5%) or AOO (3:2). Afterwards the specific airway response (Penh) and airway reactivity to methacholine (airway resistance) were assessed. Mice were sacrificed 48 hours after the challenge. Total and differential cell counts, TNF-a and MIP-2, were assessed in broncho-alveolar lavage (BAL) fluid. Total serum IgE, IgG1 and IgG2a levels were measured. Lymphocyte subpopulations (CD4+, CD8+, CD25+, CD19+) were determined in the auricular (ALN) and cervical (CLN) lymph nodes. IL-4 and IFN-γ release, in vitro, after concanavalin A (ConA) stimulation, was assessed.
Results: The EC3 of TDA in the LLNA is 19.1%. In the mouse model of chemical-induced asthma, only TDI induced a ventilatory response (8.5-fold increase in Penh after challenge; 1.7-fold increase in AHR), inflammatory changes (2.5 x104 neutrophils) and immunological changes (increased Th-, Tc- and B-lymphocytes, IL-4, IFN-γ and total serum IgE). TDA did not show a response. Mice sensitized with TDI and challenged with TDA also did not show any airway or inflammatory response, although they had increased levels of total serum IgE. Mice sensitized with TDA and challenged with TDI did not show any response.
Conclusion: According to the classification of sensitizers in the LLNA, TDA is a weak dermal sensitizer. In the mouse model of chemical-induced asthma, TDA does not act as a respiratory sensitizer, at the concentration used. No cross-reactivity between TDI and TDA was found.
Publication status: accepted
KU Leuven publication type: AMa
Appears in Collections:Occupational, Environmental and Insurance Medicine (-)
Environment and Health - miscellaneous
# (joint) last author

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