Phosgene (carbonyl chloride, CAS 75-44-5) is a highly reactive gas of historical interest and current industrial importance. Phosgene has also proved to be a useful model for the study of those biochemical mechanisms that lead to permeability-type pulmonary edema (adult respiratory distress syndrome). In turn, the study of phosgene-induced adult respiratory distress syndrome has provided insights leading to revised treatment strategies for exposure victims. We summarized recent findings on the mechanisms of phosgene-induced pulmonary edema and their implications for victim management. In light of that research, we also provide a comprehensive approach to the management and treatment of phosgene exposure victims.
Phosgene inhalation in concentrations greater than 1 ppm may produce a transient bioprotective vagus reflex with rapid shallow breathing in some individuals. Phosgene concentrations greater than 3 ppm are moderately irritating to eyes and upper airways. Toxic phosgene doses (greater than or equal to 30 ppm X min) inhaled into the terminal respiratory passages render the blood-air-barrier more permeable to blood plasma, which gradually collects in the lung. Some time passes, however, until the collection of fluid provokes signs and symptoms. This period in which the patient experiences relative well-being is known as the clinical latent phase. The clinical symptoms which follow and the pathological changes underlying them are discussed in detail; dose-effect relationships are demonstrated. The regression phase after poisoning has been overcome is briefly sketched.
Toluene diisocyanate (TDI) is an important industrial intermediate used in manufacturing flexible polyurethane (PUR) foams, surface coatings, cast elastomers, sealants, and adhesives. In this review long-term trends in workplace exposures to TDI are assessed in both the producing and using industries, and respiratory health effects of TDI are evaluated in relation to workplace TDI concentrations. The key respiratory health effects associated with repeated or long-term TDI exposure are bronchial asthma and an accelerated rate of decline in lung function. In the early years of the industry, annual incidence rates of occupational asthma (OA) due to TDI ranged from 1% to as high as 5 to 6%, depending on the extent of engineering and work practice controls in the various workplaces. Since the mid-1970s, annual OA incidence rates have been <1%, where 8 h TDI concentrations have been maintained below 5 ppb as determined by personal monitoring, even where short-termTDI concentrations above 20 ppb and less frequently above 40 ppb were routinely detected. In these latter settings, there is evidence that the majority of OA cases may be attributable to TDI concentrations well above 20 ppb associated with overexposure incidents. Further study is needed regarding the role of such incidents in inducing respiratory sensitization. Cross-sectional and longitudinal studies of lung function have indicated that continued exposure after development of work-related respiratory symptoms can lead to transient or accelerated fixed declines in forced expiratory volume in 1 sec (FEV1). These findings are congruent with the FEV1 declines demonstrated in general population studies of persons with persistent bronchial hyperresponsiveness or nonoccupational asthma. More recent longitudinal studies in settings with ongoing medical surveillance have provided no consistent evidence of accelerated FEV1 loss among employees exposed up to 5 ppb TDI on an 8 h time-weighted average basis.
Minimal inhalation doses (or concentrations) of phosgene necessary for the production of changes within the blood-air barrier were determined in rats. At least 50 ppm.min (5 ppm X 10 min) was necessary for the production of alveolar oedema (the minimal effective phosgene concentration being 5 ppm). While the smallest phosgene dose to produce an increase in pulmonary lavage protein content was also 50 ppm.min and while the smallest phosgene dose to produce widening of pulmonary interstices was 25 ppm.min, there was no phosgene threshold concentration (down to 0.1 ppm) for these two latter parameters, which are assumed to be indicators of physiological compensatory mechanisms within the blood-air barrier. The primary localisation of pulmonary damage seemed to depend on the concentration of phosgene used: at low concentrations (0.1-2.5 ppm) the changes were primarily located at the transition from terminal bronchioles to the alveolar ducts; at higher concentrations (5 ppm) damage to the alveolar pneumocytes (type I) was more conspicuous.
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