PMID- 15371179
OWN - NLM
STAT- MEDLINE
DCOM- 20041005
LR  - 20191026
IS  - 0895-8378 (Print)
IS  - 0895-8378 (Linking)
VI  - 16
IP  - 5
DP  - 2004 May
TI  - Respiratory allergy to trimellitic anhydride in rats: concentration-response 
      relationships during elicitation.
PG  - 259-69
AB  - The present study investigated whether airway responses of sensitized rats to 
      trimellitic anhydride (TMA) were concentration dependent and whether these were 
      related to irritation by TMA. Groups of BN and Wistar rats were sensitized by two 
      dermal applications of TMA (50% w/v, followed by 25% w/v in vehicle). Controls 
      received vehicle (acetone-olive oil 4:1, v/v). All animals were challenged 3 wk 
      after the first sensitization by inhalation of one of a range of concentrations 
      of TMA (0.2-61 mg/m3 for BN rats, 15-250 mg/m3 for Wistar rats). Breathing 
      pattern, breathing frequency, and tidal volume were measured before, during, and 
      after challenge to assess allergic and irritative airway responses. One day after 
      challenge, nonspecific airway responsiveness to a range of concentrations of 
      methacholine was measured. At necropsy on the same day, blood was withdrawn for 
      measuring total serum immunoglobulin E (IgE) and organs were weighed. Larynx, 
      trachea and lungs were examined histopathologically. In BN rats, TMA 
      sensitization elevated total IgE levels; subsequent inhalation challenge with 2 
      mg/m3 of TMA and higher caused laryngeal inflammation with squamous epithelial 
      metaplasia, and pulmonary hemorrhages. Concentration-related decreases in 
      breathing frequency and alterations in breathing pattern, which differed from the 
      irritation-induced pattern, were also observed at these levels. Inhalation 
      challenge with TMA concentrations of 12 mg/m3 and higher increased lung weight. 
      Increased nonspecific airway responsiveness was observed at the 2 next higher 
      tested concentrations of 46 and 61 mg/m3. In unsensitized BN rats, only laryngeal 
      squamous metaplasia was observed, albeit at higher challenge concentrations of 
      TMA, and decreased breathing frequency, a typical breathing pattern 
      characteristic of irritation. Identically sensitized Wistar rats showed airway 
      inflammation and pulmonary hemorrhages upon challenge with TMA, but no functional 
      changes, even at distinctly irritating concentrations of TMA up to 250 mg/m3. In 
      conclusion, TMA challenge of sensitized BN rats caused challenge 
      concentration-related allergic airway inflammation, asthmalike changes in 
      breathing pattern, and increased nonspecific airway responsiveness. The lowest 
      no-observed-effect level (NOEL) based on the most sensitive endpoint investigated 
      was 0.2 mg/m3, a value that is well below the irritation concentration. The 
      presence of a NOEL in the sensitized BN rat suggests that assessment of safe 
      human exposure levels is feasible.
CI  - Copyright Taylor & Francis Inc.
FAU - Arts, Josje
AU  - Arts J
AD  - Toxicology Division, TNO Nutrition and Food Research, Zeist, The Netherlands. 
      j.arts@voeding.tno.nl
FAU - de Koning, Martijn
AU  - de Koning M
FAU - Bloksma, Nanne
AU  - Bloksma N
FAU - Kuper, C
AU  - Kuper C
LA  - eng
PT  - Journal Article
PL  - England
TA  - Inhal Toxicol
JT  - Inhalation toxicology
JID - 8910739
RN  - 0 (Allergens)
RN  - 0 (Phthalic Anhydrides)
RN  - 0W5ETF9M2K (Methacholine Chloride)
RN  - 37341-29-0 (Immunoglobulin E)
RN  - 80T61EUU7H (trimellitic anhydride)
SB  - IM
MH  - Administration, Inhalation
MH  - Allergens/administration & dosage/*toxicity
MH  - Animals
MH  - Body Weight/drug effects
MH  - Bronchial Provocation Tests
MH  - Dose-Response Relationship, Drug
MH  - Female
MH  - Immunoglobulin E/blood
MH  - Lung/*drug effects/pathology/physiopathology
MH  - Methacholine Chloride/administration & dosage
MH  - No-Observed-Adverse-Effect Level
MH  - Organ Size/drug effects
MH  - Phthalic Anhydrides/administration & dosage/*toxicity
MH  - Rats
MH  - Rats, Inbred BN
MH  - Rats, Wistar
MH  - Respiratory Function Tests
MH  - Respiratory Hypersensitivity/*chemically induced/immunology/pathology
EDAT- 2004/09/17 05:00
MHDA- 2004/10/06 09:00
CRDT- 2004/09/17 05:00
PHST- 2004/09/17 05:00 [pubmed]
PHST- 2004/10/06 09:00 [medline]
PHST- 2004/09/17 05:00 [entrez]
AID - XV8D8MV3JG62C19E [pii]
AID - 10.1080/08958370490427932 [doi]
PST - ppublish
SO  - Inhal Toxicol. 2004 May;16(5):259-69. doi: 10.1080/08958370490427932.