Skip Navigation


ToxSci Advance Access originally published online on June 27, 2003
This Article
Right arrow Full Text Freely available
Right arrow FREE Full Text (PDF) Freely available
Right arrow All Versions of this Article:
75/1/89    most recent
kfg171v1
Right arrow Alert me when this article is cited
Right arrow Alert me if a correction is posted
Services
Right arrow Email this article to a friend
Right arrow Similar articles in this journal
Right arrow Similar articles in ISI Web of Science
Right arrow Similar articles in PubMed
Right arrow Alert me to new issues of the journal
Right arrow Add to My Personal Archive
Right arrow Download to citation manager
Right arrow Search for citing articles in:
ISI Web of Science (12)
Right arrowRequest Permissions
Right arrow Disclaimer
Google Scholar
Right arrow Articles by Klink, K. J.
Right arrow Articles by Meade, B. J.
Right arrow Search for Related Content
PubMed
Right arrow PubMed Citation
Right arrow Articles by Klink, K. J.
Right arrow Articles by Meade, B. J.
Social Bookmarking
Add to CiteULike   Add to Connotea   Add to Del.icio.us  
What's this?

Toxicological Sciences 75, 89-98 (2003)
Copyright © 2003 by the Society of Toxicology

IMMUNOTOXICOLOGY

Dermal Exposure to 3-Amino-5-mercapto-1,2,4-triazole (AMT) Induces Sensitization and Airway Hyperreactivity in BALB/c Mice

K. J. Klink and B. J. Meade

National Institute for Occupational Safety and Health, Morgantown, West Virginia 26505

A cluster of occupational asthma (OA) cases associated with occupational exposure to 3-amino-5-mercapto-1,2,4-triazole (AMT) and N-(2,6-difluorophenyl)-5-methyl-[1,2,4]triazolo[1,5-a]pyrimidine-2-sulfonamide (DE498) in a herbicide producing plant was previously reported by the National Institute for Occupational Safety and Health. Due to the limited toxicological data available for these chemicals, murine studies were undertaken to evaluate the toxicity and sensitization potential of these two agents. No signs of systemic toxicity as evaluated by body and selected organ weights or irritancy were observed following dermal exposure to concentrations up to 25% (w/v) AMT in BALB/c mice. DE498 tested negative for sensitization potential in both the TOPKAT QSAR model and in vivo in the Local Lymph Node Assay (LLNA), while AMT tested positive in both TOPKAT QSAR and the LLNA. Evaluation of the potential for AMT to induce contact hypersensitivity using the MEST yielded negative results. Cytokine evaluation and phenotypic analysis of draining lymph node (DLN) cells demonstrated an increase in IL-4 and IgE+B220+ cells 4 and 10 days post initial exposure, respectively. Following dermal exposure 7 days a week for 35 days, animals exposed to up to 25% AMT demonstrated a dose-dependent elevation in total serum IgE and an increase in airway hyperreactivity upon methacholine challenge. Following intratracheal challenge with AMT, pulmonary histopathology revealed a dose-dependent suppurative and histiocytic alveolitis in these animals. These studies indicate that DE498 does not induce sensitization following dermal exposure; however, AMT was identified as a sensitizer with the potential to induce airway hyperreactivity.

Key Words: 3-amino-5-mercapto-1,2,4-triazole (AMT); N-(2,6-difluorophenyl)-5-methyl-[1,2,4]triazolo[1,5-a]pyrimidine-2-sulfonamide (DE498); airway hyperreactivity; dermal sensitization; IgE.


Add to CiteULike CiteULike   Add to Connotea Connotea   Add to Del.icio.us Del.icio.us    What's this?


This article has been cited by other articles:


Home page
 Toxicol SciHome page
A. K. Farraj, E. Boykin, N. Haykal-Coates, S. H. Gavett, D. Doerfler, and M. Selgrade
Th2 Cytokines in Skin Draining Lymph Nodes and Serum IgE Do Not Predict Airway Hypersensitivity to Intranasal Isocyanate Exposure in Mice
Toxicol. Sci., November 1, 2007; 100(1): 99 - 108.
[Abstract] [Full Text] [PDF]

Home page
 Occup. Environ. Med.Home page
K. Kreiss
Emerging opportunities to prevent occupational lung disease
Occup. Environ. Med., August 1, 2007; 64(8): 499 - 500.
[Full Text] [PDF]

Home page
 Toxicol SciHome page
M. Selgrade, E. H. Boykin, N. Haykal-Coates, M. R. Woolhiser, C. Wiescinski, D. L. Andrews, A. K. Farraj, D. L. Doerfler, and S. H. Gavett
Inconsistencies between Cytokine Profiles, Antibody Responses, and Respiratory Hyperresponsiveness following Dermal Exposure to Isocyanates
Toxicol. Sci., November 1, 2006; 94(1): 108 - 117.
[Abstract] [Full Text] [PDF]

Home page
 Toxicol SciHome page
M. P. Holsapple, D. Jones, T. T. Kawabata, I. Kimber, K. Sarlo, M. K. Selgrade, J. Shah, and M. R. Woolhiser
Assessing the Potential to Induce Respiratory Hypersensitivity
Toxicol. Sci., May 1, 2006; 91(1): 4 - 13.
[Abstract] [Full Text] [PDF]

Home page
 Toxicol SciHome page
J. A. J. Vanoirbeek, M. Tarkowski, J. L. Ceuppens, E. K. Verbeken, B. Nemery, and P. H. M. Hoet
Respiratory Response to Toluene Diisocyanate Depends on Prior Frequency and Concentration of Dermal Sensitization in Mice
Toxicol. Sci., August 1, 2004; 80(2): 310 - 321.
[Abstract] [Full Text] [PDF]


Disclaimer: Please note that abstracts for content published before 1996 were created through digital scanning and may therefore not exactly replicate the text of the original print issues. All efforts have been made to ensure accuracy, but the Publisher will not be held responsible for any remaining inaccuracies. If you require any further clarification, please contact our Customer Services Department.