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Phosgene (CG) is a highly irritant gas widely used industrially as a chemical intermediate for the production of dyes, pesticides, and plastics, and can cause life-threatening pulmonar y edema within 24 hours of exposure. This study was designed to investigate acute changes in lung tissue histopathology and selected bronchoalveola r lavage uid (BALF) factors over time to determine early diagnostic indicators of exposure. Three groups of 40 male mice each were exposed to 32 mg/m 3 (8 ppm) CG for 20 minutes, and 3 groups of 40 control male mice were exposed to ltered room air for 20 minutes, both exposures were followed by room air washout for 5 minutes. At 1,4,8,12,24, 48, and 72 hours after exposure each group of mice was euthanized and processed for histopatholog y, bronchoalveola r lavage or gravimetric measurements , respectively. Over time, the histopathologica l lesions were characterized by acute changes consisting of alveolar and interstitial edema, brin and hemorrhage , followed by signi cant alveolar and interstitial ooding with in ammatory cell in ltrates and scattered bronchiolar and terminal airway epithelial degeneratio n and necrosis. From 48 to 72 hours, there was partial resolution of the edema and degenerative changes, followed by epithelial and broblastic regeneration centered on the terminal bronchiolar areas. Bronchoalveola r lavage was processed for cell differential counts, LDH, and protein determination. Comparative analysis revealed signi cant increases in both postexposur e lung wet/dry weight ratios, and early elevations of BALF LDH and protein, and later elevations in leukocytes. This article describes the use of histopathology to chronicle the temporal pulmonary changes subsequent to whole body exposure to phosgene , and correlate these changes with BALF ingredients and postexposur e lung wet weights in an effort to characterize toxic gas-induced acute lung injury and identify early markers of phosgene exposure.

A new method for measuring fluoride ion released isopropyl methylphosphonofluoridate (sarin, GB) in the red blood cell fraction was developed that utilizes an autoinjector, a large-volume injector port (LVI), positive ion ammonia chemical ionization detection in the SIM mode, and a deuterated stable isotope internal standard. This method was applied to red blood cell (RBC) and plasma ethyl acetate extracts from spiked human and animal whole blood samples and from whole blood of minipigs, guinea pigs, and rats exposed by whole-body sarin inhalation. Evidence of nerve agent exposure was detected in plasma and red blood cells at low levels of exposure. The linear method range of quantitation was 10-1000 pg on-column with a detection limit of approximately 2-pg on-column. In the course of method development, several conditions were optimized for the LVI, including type of injector insert, injection volume, initial temperature, pressure, and flow rate. RBC fractions had advantages over the plasma with respect to assessing nerve agent exposure using the fluoride ion method especially in samples with low serum butyrylcholinesterase activity.