PMID- 14514965
OWN - NLM
STAT- MEDLINE
DCOM- 20040806
LR  - 20191210
IS  - 1096-6080 (Print)
IS  - 1096-0929 (Linking)
VI  - 76
IP  - 2
DP  - 2003 Dec
TI  - Validity of methods to predict the respiratory sensitizing potential of 
      chemicals: A study with a piperidinyl chlorotriazine derivative that caused an 
      outbreak of occupational asthma.
PG  - 338-46
AB  - A piperidinyl chlorotriazine (PCT) derivative, used as a plastic UV-stabilizer, 
      caused an outbreak of occupational asthma. We verified, in BALB/c mice, the 
      sensitizing potential of PCT in comparison to a known respiratory sensitizer 
      (toluene diisocyanate [TDI]) and a known dermal sensitizer (oxazolone), using 
      three different methods in order to evaluate the validity of current models of 
      sensitization. These included the local lymph node assay (LLNA) and the mouse IgE 
      test. In addition, respiratory hyper-reactivity was assessed following a novel 
      protocol involving dermal sensitization (20 microl of a 3% solution on each ear 
      for three days) and intranasal challenge (0.1% or 1%, 10 microl per nostril on 
      day 10), followed, after 24 h, by a methacholine challenge (using whole-body 
      plethysmography), bronchoalveolar lavage, and histology. PCT was also used for 
      structure-activity relationship (SAR) models for (respiratory) sensitization. 
      High concentrations of PCT (10 and 20%) resulted in significant responses in the 
      local lymph node assay (LLNA; stimulation indices (SI) 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 sensitized 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 
      sensitizer. Based on an approved test protocol such as the LLNA and the mouse IgE 
      test, PCT proved to be a weak sensitizer when compared to TDI and oxazolone. 
      However, in a protocol involving an intranasal challenge, PCT appeared to be a 
      respiratory sensitizer of similar potency to TDI.
FAU - Vanoirbeek, Jeroen A J
AU  - Vanoirbeek JA
AD  - Pneumology (Lung Toxicology), Katholieke Universiteit Leuven, Leuven, Belgium.
FAU - Mandervelt, Cindy
AU  - Mandervelt C
FAU - Cunningham, Albert R
AU  - Cunningham AR
FAU - Hoet, Peter H M
AU  - Hoet PH
FAU - Xu, Haiyan
AU  - Xu H
FAU - Vanhooren, Hadewijch M
AU  - Vanhooren HM
FAU - Nemery, Benoit
AU  - Nemery B
LA  - eng
PT  - Comparative Study
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
PT  - Validation Study
DEP - 20030926
PL  - United States
TA  - Toxicol Sci
JT  - Toxicological sciences : an official journal of the Society of Toxicology
JID - 9805461
RN  - 0 (Adjuvants, Immunologic)
RN  - 0 (Allergens)
RN  - 0 (Piperidines)
RN  - 0 (Triazines)
RN  - 0 (piperidinyl chlorotriazine derivative)
RN  - 0W5ETF9M2K (Methacholine Chloride)
RN  - 15646-46-5 (Oxazolone)
RN  - 17X7AFZ1GH (Toluene 2,4-Diisocyanate)
RN  - 37341-29-0 (Immunoglobulin E)
SB  - IM
MH  - Adjuvants, Immunologic
MH  - Administration, Cutaneous
MH  - Allergens/administration & dosage/chemistry/*toxicity
MH  - Animals
MH  - Asthma/*chemically induced/immunology/pathology
MH  - Bronchoalveolar Lavage
MH  - Dermatitis, Allergic Contact/immunology/pathology
MH  - Dose-Response Relationship, Drug
MH  - Female
MH  - Immunoglobulin E/blood
MH  - Local Lymph Node Assay
MH  - Lung/drug effects/pathology
MH  - Lymph Nodes/*drug effects/immunology/pathology
MH  - Methacholine Chloride/pharmacology
MH  - Mice
MH  - Mice, Inbred BALB C
MH  - Occupational Exposure/*adverse effects
MH  - Oxazolone/administration & dosage/toxicity
MH  - Piperidines/administration & dosage/chemistry/*toxicity
MH  - Predictive Value of Tests
MH  - Structure-Activity Relationship
MH  - Toluene 2,4-Diisocyanate/administration & dosage/toxicity
MH  - Triazines/administration & dosage/chemistry/*toxicity
EDAT- 2003/09/30 05:00
MHDA- 2004/08/07 05:00
CRDT- 2003/09/30 05:00
PHST- 2003/09/30 05:00 [pubmed]
PHST- 2004/08/07 05:00 [medline]
PHST- 2003/09/30 05:00 [entrez]
AID - kfg235 [pii]
AID - 10.1093/toxsci/kfg235 [doi]
PST - ppublish
SO  - Toxicol Sci. 2003 Dec;76(2):338-46. doi: 10.1093/toxsci/kfg235. Epub 2003 Sep 26.