Airway responses after specific challenge of rats sensitized via skin exposure to trimellitic anhydride (TMA).
Zhang-XD; Fedan-JS; Lewis-DM; Siegel-PD
Toxicologist 2002 Mar; 66(1-S):242
TMA is a low-molecular-weight chemical that can induce production of specific IgE and occupational asthma in sensitized individuals. The respiratory tract is considered to be a major exposure route leading to immunological and airway sensitization, but the relationship between dermal exposure and subsequent airway responses to TMA is not known. Our previous work, using Brown Norway (BN) rats, demonstrated that topical skin exposure to dry TMA powder induces dose-dependent production of specific IgE. The present study investigated the airway responses to inhaled TMA of BN rats that have been sensitized dermally with TMA. Twenty mg of dry TMA powder was applied to the rat's back (clipped with scissors) on days 0, 7, 14 and 21, and occluded overnight with surgical tape. Rats were challenged by a 10 min, 40 mg/m3 TMA aerosol inhalation on day 35. Enhanced pause (Penh), an index of airway narrowing, was recorded overnight in a whole body plethysmography system. Compared to non-sensitized rats, the sensitized BN rats displayed both distinct early (EAR) and late airway responses (LAR), as noted by an increase in Penh after TMA inhalation. The EAR occurred immediately following the challenge and lasted approximately 0.5 to 1 hour. This was followed by 2 hours of normal breathing. The LAR began from 3 to 4 hours after challenge and the increase in Penh lasted up to 19 hours following exposure. This work and our previous studies demonstrate that dermal exposure to TMA powder can lead to both immunological sensitization and obstructive airway responses upon aerosol challenge. This BN rat model, with both EAR and LAR, may be valuable for further study of pathophysiological mechanisms of organic acid anhydride-induced asthma.
Animals; Respiratory-system-disorders; Skin-exposure; Sensitization; Inhalation-studies; Laboratory-animals; Pulmonary-system-disorders
Asthma and Chronic Obstructive Pulmonary Disease; Disease and Injury
The Toxicologist. Society of Toxicology 41st Annual Meeting and ToxExpo, March 17-21, 2002, Nashville, Tennessee