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ToxSci Advance Access published online on September 26, 2003
Toxicological Sciences, doi:10.1093/toxsci/kfg235
Toxicological Sciences © Society of Toxicology 2003; all rights reserved
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Received May 2, 2003; accepted August 28, 2003
© 2003 Society of Toxicology

Immunotoxicology

Validity of Methods to Predict the Respiratory Sensitising Potential of Chemicals. A Study with a Piperidinyl Chlorotriazine Derivative That Caused an Outbreak of Occupational Asthma

Jeroen A. J. Vanoirbeek 1, Cindy Mandervelt 1, Albert R. Cunningham 2, Peter H. M. Hoet 1, Haiyan Xu 1, Hadewijch M. Vanhooren 1, and Benoit Nemery 1*

1 Pneumology (Lung Toxicology), Katholieke Universiteit Leuven, Leuven, Belgium
2 Department of Environmental Studies, Louisiana State University, Baton Rouge, LA, USA

* To whom correspondence should be addressed. E-mail: ben.nemery{at}med.kuleuven.ac.be.


  Abstract

A piperidinyl chlorotriazine (PCT) derivative, used as a plastic UV-stabiliser, caused an outbreak of occupational asthma. We verified, in BALB/C mice, the sensitising potential of PCT in comparison with a known respiratory sensitiser (toluene diisocyanate, TDI) and a known dermal sensitiser (oxazolone), using three different methods, in order to evaluate the validity of current models of sensitisation. These included the local lymph node assay (LLNA) and the mouse IgE-test. In addition, respiratory hyperreactivity was assessed following a novel protocol, involving dermal sensitisation (20 µl of a 3% solution on each ear for three days) and intranasal challenge (0.1 or 1%, 10µl per nostril, on day 10), followed after 24 h by a methacholine challenge (using whole body plethysmography), bronchoalveolar lavage and histology. PCT was also subjected to structure-activity relationship (SAR) models for (respiratory) sensitisation.

High concentrations of PCT (10% and 20%) resulted in significant responses in the LLNA (stimulation indices of 2.7 ± 0.9 and 3.2 ± 0.6, respectively). The mouse IgE-test was positive with 20% PCT only. Methacholine responsiveness was increased only in previously sensitised mice receiving a challenge with TDI or PCT. However, there was no evidence for pulmonary inflammation. The SAR studies indicated that PCT could be a respiratory sensitiser.

Based on an approved test protocol, such as the LLNA, and the mouse IgE test, PCT proved to be a weak sensitiser, compared to TDI and oxazolone. However, in a protocol involving an intranasal challenge, PCT appeared to be a respiratory sensitiser of similar potency as TDI.

Key Words: Local Lymph Node Assay, chemical sensitisation, asthma, piperidinyl chlorotriazine, toluene diisocyanate .


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