PMID- 12832659
OWN - NLM
STAT- MEDLINE
DCOM- 20040802
LR  - 20121115
IS  - 1096-6080 (Print)
IS  - 1096-0929 (Linking)
VI  - 75
IP  - 1
DP  - 2003 Sep
TI  - Dermal exposure to 3-amino-5-mercapto-1,2,4-triazole (AMT) induces sensitization 
      and airway hyperreactivity in BALB/c mice.
PG  - 89-98
AB  - 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.
FAU - Klink, K J
AU  - Klink KJ
AD  - National Institute for Occupational Safety and Health, Morgantown, West Virginia 
      26505, USA.
FAU - Meade, B J
AU  - Meade BJ
LA  - eng
GR  - Y1-ES-0001-02/ES/NIEHS NIH HHS/United States
PT  - Journal Article
PT  - Research Support, U.S. Gov't, P.H.S.
DEP - 20030627
PL  - United States
TA  - Toxicol Sci
JT  - Toxicological sciences : an official journal of the Society of Toxicology
JID - 9805461
RN  - 0 (3-amino-5-mercapto-1,2,4-triazole)
RN  - 0 (Cytokines)
RN  - 0 (Pyrimidines)
RN  - 0 (RNA, Messenger)
RN  - 0 (Sulfonamides)
RN  - 0 (Triazoles)
RN  - 207137-56-2 (Interleukin-4)
RN  - 37341-29-0 (Immunoglobulin E)
RN  - X89F0S6LW8 
      (N-(2,6-difluorophenyl)-5-methyl(1,2,4)-triazol(1,5-a)pyrimidine-2-sulfonamide)
SB  - IM
MH  - Administration, Cutaneous
MH  - Animals
MH  - Cytokines/metabolism
MH  - Dose-Response Relationship, Drug
MH  - Female
MH  - Immunoglobulin E/blood
MH  - Interleukin-4/biosynthesis/genetics
MH  - Lung/drug effects/pathology
MH  - Mice
MH  - Mice, Inbred BALB C
MH  - Mice, Inbred CBA
MH  - Models, Biological
MH  - Occupational Exposure
MH  - Phenotype
MH  - Pyrimidines/administration & dosage/toxicity
MH  - Quantitative Structure-Activity Relationship
MH  - RNA, Messenger/biosynthesis
MH  - Respiratory Hypersensitivity/*chemically induced/metabolism
MH  - Sulfonamides/administration & dosage/toxicity
MH  - Time Factors
MH  - Triazoles/administration & dosage/*toxicity
EDAT- 2003/07/02 05:00
MHDA- 2004/08/03 05:00
CRDT- 2003/07/02 05:00
PHST- 2003/07/02 05:00 [pubmed]
PHST- 2004/08/03 05:00 [medline]
PHST- 2003/07/02 05:00 [entrez]
AID - kfg171 [pii]
AID - 10.1093/toxsci/kfg171 [doi]
PST - ppublish
SO  - Toxicol Sci. 2003 Sep;75(1):89-98. doi: 10.1093/toxsci/kfg171. Epub 2003 Jun 27.