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ToxSci Advance Access originally published online on March 30, 2009
Toxicological Sciences 2009 109(2):256-264; doi:10.1093/toxsci/kfp065
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© The Author 2009. Published by Oxford University Press on behalf of the Society of Toxicology. All rights reserved. For permissions, please email: journals.permissions@oxfordjournals.org

Is Toluene Diamine a Sensitizer and is there Cross-Reactivity between Toluene Diamine and Toluene Diisocyanate?

Jeroen A. J. Vanoirbeek, Vanessa De Vooght, Nicholas Synhaeve, Benoit Nemery and Peter H. M. Hoet1

Research Unit Lung Toxicology, Katholieke Universiteit Leuven, B-3000 Leuven, Belgium

1 To whom correspondence should be addressed at Research Unit of Lung Toxicology, Katholieke Universiteit Leuven, Herestraat 49 bus 706, B-3000 Leuven, Belgium. Fax: +32-16-34-71-24. E-mail: peter.hoet{at}med.kuleuven.be.

Received December 19, 2008; accepted March 14, 2009


  Abstract

Toluene diamine (TDA) is formed when toluene diisocyanate (TDI), a potent sensitizer, comes in contact with an aqueous environment. The sensitizing capacity of TDA and the cross-reactivity between TDI and TDA are unknown. 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 capacity of TDA to elicit an asthmatic response and to determine the cross-reaction with TDI, a locally developed experimental mouse model of chemical-induced asthma was used. On days 1 and 8, BALB/c mice received 20 µl of TDI (0.3%), TDA (20%), or AOO (4:1) on each ear. On day 15, they received an intranasal instillation of TDI (0.1%), TDA (0.5%) or AOO (3:2). The EC3 of TDA in the LLNA is 19%. In the model of chemical-induced asthma, TDI induced a ventilatory response [increased Penh after challenge; increased airway hyperreactivity (AHR)], inflammatory changes (bronchoalveolar lavage neutrophils), and immunological changes (increased CD19+ lymphocytes, IL-4 and total serum IgE), whereas TDA did not show any of these responses. 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. According to the classification of sensitizers in the LLNA, TDA is a weak dermal sensitizer. In the experimental 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.

Key Words: TDI; TDA; occupational asthma; murine model; cross-reactivity.


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