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mation, rhinorrhea, epistaxis, hacking cough; (4-16 hrs) sinus pain, severe epistaxis; (16-24 hrs) severe cough; (24-48 hrs) severe dyspnea, pulmonary edema; (48-72 hrs) bronchopneumonia. Delayed effects measured after two years included: chronic bronchitis, asthma, rhinopharyngitis, tracheobronchitis, laryngitis, recurrent pneumonia and bronchiectasis. In summary, then, overexposure to nitrogen mustards has caused both airway reactions and parenchymal damage with increased risk of pulmonary infection.

Since the respiratory conditions described in instances of severe overexposure to nitrogen mustards have been both acute and chronic, there is evidence that some level of exposure to these agents can cause both severe acute and chronic respiratory disease.

However, there is little evidence available on the effects of lower level acute exposure and none apparently on brief exposures which are not too excessive. In the absence of follow-up studies that directly address the question, much of the exploration must involve examining indirect evidence from the study of compounds which might behave similarly. In order to evaluate the respiratory health risk associated with repeated brief overexposures at lower levels, review of indirect evidence will focus on examining the link between acute and chronic respiratory responses to such agents.

One central difficulty in examining this question is the absence of knowledge about the early stages of environmentally related pulmonary diseases coupled with almost no knowledge on the natural (longitudinal) evolution of the clinical conditions. Thus there is little to guide us in what is the appropriate disease model and what pattern(s) of exposure are relevant to disease etiology.

REVIEW OF AGENTS CAUSING ACUTE AND CHRONIC RESPIRATORY EFFECTS

The following agents have been selected to illustrate the range of exposure-effect relationships that may be relevant to the effects of the mustards. It will be noted that the agents selected have been shown to result in (to cause) a mix of respiratory conditions: Exposures to irritant gases (chlorine, SO2, combustion products); exposures to materials of plant origin (cotton); exposures to chemicals (isocyanates); and exposures to inorganic dusts (silica, beryllium, asbestos).

Chlorine

Since chlorine gas is such an irritating substance, there are a number of reports of overexposures with documented acute respiratory effects.



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