The pathologic and immunologic response to inhaled trimellitic anhydride in rats*1

Leach, Chester L.

doi:10.1016/0041-008x(87)90085-8

Cited by 24 publications

(8 citation statements)

References 16 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…However, this may be different in sensitized subjects, since at concentrations as low as 0.04 mg/m 3 pulmonary hemorrhages have been observed in sensitized rats (Leach et al, 1987).…”

Section: Discussionmentioning

confidence: 99%

Respiratory Irritation by Trimellitic Anhydride in Brown Norway and Wistar Rats

Arts¹,

Koning²,

Bloksma³

et al. 2001

Inhalation Toxicology

View full text Add to dashboard Cite

Several acid anhydrides are known for their sensitizing and irritative properties. Since both irritation and respiratory allergy can cause changes of lung function, proper testing of allergen-dependent effects on the respiratory tract requires knowledge of the respiratory irritant effects. To study the latter effects, groups of female Brown Norway (BN) and Wistar rats were exposed for 30 min to a range of concentrations (10 to 300 mg/m(3)) of the well-known respiratory allergen trimellitic anhydride (TMA). Breathing pattern and frequency were monitored before, during, and after exposure. Animals were necropsied and lung weights were determined 1 day after exposure. In BN rats, changes in breathing pattern were seen at levels of 29 mg/m(3) and higher and decreases in frequency at 60 mg/m(3) and higher, whereas in Wistar rats changes in both pattern and frequency (increases followed by decreases) were seen at levels of 34 mg/m(3) and higher. Changes in breathing pattern consisted of a spiked form instead of a wave form of the respiratory cycle, with a pause between breaths at the end of expiration. The length of the pause increased with increasing concentrations of TMA while the duration of the respiratory cycle decreased slightly, implying that breathing frequency was mainly determined by the magnitude of the increase in pause. These reversible changes in breathing pattern and frequency were considered to be suggestive of lower airway irritation, rather than upper airway irritation. No concentration-related changes in lung weights were observed. The highest level at which no acute airway irritation as based on both breathing pattern and frequency was observed in both rat strains was 14 mg/m(3).

show abstract

“…However, this may be different in sensitized subjects, since at concentrations as low as 0.04 mg/m 3 pulmonary hemorrhages have been observed in sensitized rats (Leach et al, 1987).…”

Section: Discussionmentioning

confidence: 99%

Respiratory Irritation by Trimellitic Anhydride in Brown Norway and Wistar Rats

Arts¹,

Koning²,

Bloksma³

et al. 2001

Inhalation Toxicology

View full text Add to dashboard Cite

show abstract

“…TMA-induced pulmonary haemosiderosis is the most firmly established occupationallyrelated diffuse pulmonary haemorrhage syndrome, which has been reported in both humans and experimental animals [2]. An immunological basis for the disease was assumed because immunoglobulin (Ig)-A, IgE and IgG antibodies to trimellityl proteins were detected in human [3], and a correlation between haemorrhagic lung foci and serum antibodies to radiolabelled TMA rat serum albumin was demonstrated in rats after inhalation of TMA [4].…”

mentioning

confidence: 99%

Haemorrhagic hypersensitivity pneumonitis due to naphthylene-1,5-diisocyanate

Merget¹,

Marczyński²,

Chen³

et al. 2002

Eur Respir J

View full text Add to dashboard Cite

Symptoms of hypersensitivity pneumonitis and massive pulmonary haemorrhage occurred in a 24-yr-old male shortly after occupational exposure to naphthylene-1,5-diisocyanate (NDI).The present examination was performed ∼1-yr after the initial life-threatening haemoptysis and following an uneventful recovery after resection of the middle lobe, which had been identified bronchoscopically as the bleeding source. Histological re-examination of the lung was compatible with hypersensitivity pneumonitis.After a chamber challenge with NDI (5 parts per billion (ppb) for 10 min, 10 ppb for 110 min), rales were heard in both lungs, and a fall in vital capacity and partial pressure of arterial oxygen as well as a rise in body temperature were documented. Isocyanate-specific immunoglobulin-G antibodies could not be detected in the patient's serum, possibly due to the long period without exposure to isocyanates.The authors conclude that naphthylene-1,5-diisocyanate may cause immunological pulmonary haemorrhage. The underlying disease is consistent with hypersensitivity pneumonitis and may be triggered by low concentrations of the diisocyanate.

show abstract

“…This result conflicts with that of SPF SD rats reported by Leach et ai. [5]. In our preliminary exper iments, only 1 of 8 SPF SD rats exposed to TMA in halation developed slight pulmonary hemorrhages.…”

Section: Discussionmentioning

confidence: 99%

“…The measurements of hemagglutination, complement fixation and PCA titers of these fractions were performed (see Materials and Methods). The protein recovery and the corresponding subclass are also included in this table. sions associated with TM-spccific antibody and the profiles resembled human syndromes [5]. TMA is a haptenic substance incapable of stimulating the im mune system by itself without carrier substances.…”

Section: Discussionmentioning

confidence: 99%

“…3]. To further investigate the mechanisms of immunopathogenic response induced by TMA inhalation, an experimental animal model of lung injury caused by TMA inhalation was established by Leach et al [5] and by Zeiss et al [6] using specific pathogen-free (SPF) Sprague-Dawley (SD) rats. The results suggested that the inhalation of TMA was a significant stimulus of a systemic immune response that occurred parallel with lung injury.…”

Section: Introductionmentioning

confidence: 99%

See 1 more Smart Citation

Experimental Lung Injury Induced by Trimellitic Anhydride Inhalation on Guinea Pigs

Tao¹,

Sugiura²,

Nakamura³

et al. 1991

Int Arch Allergy Immunol

View full text Add to dashboard Cite

Trimellitic anhydride (TMA) causes lung injury by inhalation exposure in humans. In order to investigate more precisely the mechanism of lung injury by TMA, an experimental animal model of TMA-induced lung injury was established. Guinea pigs were intramuscularly injected with trimellitylated bovine serum albumin (TM BSA) with complete Freund’s adjuvant (CFA). Appreciable amounts of antibodies against TM epitopes were detected in the sera of these animals. Guinea pigs that were passively sensitized with anti-TM antisera as well as the actively immunized animals developed hemorrhagic pneumonitis after TMA inhalation. It is well recognized that hyperimmune antisera of guinea pigs contain two subclasses of IgG antibodies, IgG1 and IgG2, which are known as homocytotropic and heterocytotropic antibodies, respectively. To determine the role of these antibodies in the airway injury with alveolar hemorrhages, they were isolated by gel filtration and by ion exchange column chromatography, and the guinea pigs that were sensitized with each of these antibodies were exposed to TMA inhalation. The extent of lung injury in these animals was quantitatively determined by the measurements of lung extravasation of Evans blue dye injected intravenously after TMA inhalation. Significant increases in the extravasation of dye were observed in both animal groups sensitized with IgG1 and IgG2 antibodies. In addition, results obtained with heat-treated antisera and IgG1 antibody did not significantly differ from those obtained with untreated samples. These results suggest that the lung injury resulting from TMA inhalation exposure can be induced with humoral antibodies, not only IgG1 but also IgG2, and that at least two types of allergic reactions are involved in the pathogenesis of lung injury.

show abstract

The pathologic and immunologic response to inhaled trimellitic anhydride in rats*1

Cited by 24 publications

References 16 publications

Respiratory Irritation by Trimellitic Anhydride in Brown Norway and Wistar Rats

Respiratory Irritation by Trimellitic Anhydride in Brown Norway and Wistar Rats

Haemorrhagic hypersensitivity pneumonitis due to naphthylene-1,5-diisocyanate

Experimental Lung Injury Induced by Trimellitic Anhydride Inhalation on Guinea Pigs

Contact Info

Product

Resources

About