Asthmalike biphasic airway responses in Brown Norway rats sensitized by dermal exposure to dry trimellitic anhydride powder.
BACKGROUND
Trimellitic anhydride (TMA) can induce specific IgE and occupational asthma. The significance of dermal exposure to TMA in immunologic sensitization and on subsequent airway responses is not clearly known. An animal model displaying both an early-phase airway response (EAR) and a late-phase airway response (LAR) after sensitization and subsequent inhalation challenge to a low-molecular-weight chemical has not been previously reported.


OBJECTIVE
The present study investigated EAR and LAR after TMA inhalation challenge in Brown Norway rats sensitized by skin exposure to TMA dry powder.


METHODS
Twenty milligrams of dry TMA powder was applied to the skin of each clipped rat's dorsum on days 0, 7, 14, and 21 and occluded overnight with surgical tape. Rats were challenged for 10 minutes with 0.2 to 40 mg/m(3) of TMA aerosol after day 35. Enhanced pause (an index of airway resistance) was recorded overnight in a whole-body plethysmography system. Specific IgE and pulmonary eosinophilia were also measured.


RESULTS
Concentration-dependent responses to TMA were observed: provocation with 0.2 mg/m(3) produced no response; 1 mg/m(3) induced only EAR; and 5 mg/m(3) and 40 mg/m(3) induced both EAR and LAR. Specific IgE was positive; airway eosinophilic inflammation was observed.


CONCLUSIONS
TMA powder applied to the skin can lead to both immunologic sensitization and subsequent dose-dependent biphasic airway responses after TMA aerosol challenge.
Zhang
Xing-Dong
XD
Health Effects Laboratory Division, National Institute for Occupational Safety and Health, Centers for Disease Control and Prevention. Morgantown, WV, USA.
Fedan
Jeffrey S
JS
Lewis
Daniel M
DM
Siegel
Paul D
PD
D000287:Administration, Topical; D000485:Allergens / Q000008:administration & dosage / Q000009:adverse effects / Q000276:immunology; D000818:Animals; D001249:Asthma / Q000209:etiology / Q000276:immunology / Q000473:pathology / Q000503:physiopathology*; D016535:Bronchial Hyperreactivity; D001985:Bronchial Provocation Tests; D004195:Disease Models, Animal; D006801:Humans; D008168:Lung / Q000276:immunology / Q000473:pathology; D008297:Male; D009784:Occupational Diseases / Q000209:etiology / Q000276:immunology / Q000473:pathology / Q000503:physiopathology*; D010796:Phthalic Anhydrides / Q000008:administration & dosage / Q000009:adverse effects / Q000276:immunology; D011208:Powders; D051381:Rats; D011914:Rats, Inbred BN; D013997:Time Factors
D000485:Allergens; D010796:Phthalic Anhydrides; D011208:Powders; C015559:trimellitic anhydride