Marion G. Buck

Acute Exposure to Low-Level Methyl Tertiary-Butyl Ether (MTBE): Human Reactions and Pharmacokinetic Response

AbstractThis two-part investigation assessed the effects of 1-h exposures to methyl tertiary-butyl ether (MTBE) at an ambient concentration of 1.7 ppm on healthy adults. In one part, four subjects participated in a pharmacokinetic study of blood levels of MTBE. Concentration in blood rose 20-fold from baseline to 17 μg/L by the end of exposure and declined to one-half that level at 40 min after exposure. In another part, 43 subjects participated in a double-blind study of reactions to exposures to MTBE (1.7 ppm), to a mixture of 17 volatile organic compounds (VOCs) (7.1 ppm), and to air. Subjects rated symptoms (e.g., irritation, headache, mental fatigue), their mood, and various environmental attributes (e.g., odor, air quality, temperature), and also took computerized performance tests during exposures. Measures of eye irritation (e.g., tear-film breakup, eye redness) and nasal inflammation (i.e., measurement of polymorphonuclear neutrophilic leukocytes, PMNs) were taken before and after exposure as obj...

Byssinosis: Airway constrictor response to cotton bracts

Inhalation of aqueous extracts of cotton bracts by healthy human volunteers induces reversible lung function changes and symptoms similar to those experienced by cotton textile workers with byssinosis. This airway constrictor response, maximal after 90–120 min, occurred in 95 out of 105 volunteers. This explains why byssinosis is highly prevalent under adverse conditions in cotton textile mills. The airway constrictor activity is retained in purified extracts of the cotton bracts which contain a small molecular (< 1,000 daltons), watersoluble, heat-stable compound.

Airway responses to the inhalation of cotton dust and cotton bract extracts.

Background: Exposure to dust in the cotton industry is associated with respiratory dysfunction. Healthy subjects challenged with cotton bract extract (CBE) develop transient airway hyperresponsiveness. CBE, a major component of cotton dust, is potentially an important agent for studying byssinosis. Objectives: To compare airway responses to cotton dust extract (CDE) and CBE in healthy subjects. Methods: In 21 healthy, non-smoking subjects we compared the effects of CBE and CDE in a double-blind random order, following a 10-min aerosol inhalation. The response to methacholine (MCh) 2 h following CBE or CDE was measured. Lung function was recorded using maximal (MEFV) and partial expiratory flow volume (PEFV) curves, measuring MEF at 60% of baseline vital capacity below total lung capacity [MEF40%(P)] on the PEFV curve. Responders were subjects who developed a 20% or greater fall in MEF40%(P) following extract challenge. Endotoxin levels were low for CBE (5.71 EU/mg) and CDE (31.88 EU/mg). Results: There were 18 responders to CBE and 17 responders to CDE.The average maximal falls in MEF40%(P) were 70 ± 4.9 and 70 ± 4.4% of baseline (nonsignificant) following CBE and CDE, respectively. All subjects enhanced their MCh response following CBE or CDE. The MCh dose which reduced MEF40%(P) by 40% was identical for CBE and CDE (1.3 µg/ml). Conclusions: We conclude that CBE and CDE exert similar physiologic effects.

Skin testing with an aqueous extract of cotton bract

Airway challenge with cotton bract extract (CBE) causes reversible bronchospasm in most volunteers never before exposed to CBE or the textile industry. Lung function abnormalities develop slowly after inhalation with a maximum effect reached within 2 hours and lung function slowly improving thereafter. When CBE was injected intradermally in three naive subjects with negligible airway response to CBE, we observed an initial wheal-and-flare reaction within minutes followed by erythema and subsequent induration that persisted for 24 to 48 hours. Microscopic examination of skin biopsy specimens obtained during the course of these reactions revealed edema in the early phase followed by perivascular infiltration of a mixed cellular nature in the subsequent stages of the reaction. Degranulation of mast cells was noted throughout the course of the reaction. These findings indirectly suggest that a nonspecific inflammatory reaction initiated by mast cell-derived mediators and sustained by the presence of infiltrating cells may be responsible for some of the airway effects observed in byssinosis.