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been shown to be disabling. Relevant to the questions being considered here is that exposures in one instance as brief as one week and in several instances occurring for less than 10 weeks have resulted in disease certified for inclusion in the Beryllium Registry established at the Massachusetts General Hospital.76

Silica exposures are generally considered important only for chronic disease. There is, however, the condition of acute silicosis caused by relatively short-term high intensity exposures to very fine silica particulate.77 Exposures as brief as six months have been associated with acute silicosis. But even in the absence of such severe overexposures and acute clinical disease, there is evidence that even low level exposures not associated with clinical symptoms or chest X-ray abnormality can result in irreversible pathology.78

Asbestos exposures similarly are noted for causing chronic respiratory illness as well as cancer. Brief high exposures are not recognized to cause respiratory complaints. However, brief exposures (on average less than four years) have been associated with increased respiratory symptoms and decreased vital capacity.79

THE FUNDAMENTAL QUESTION

Narrowly Structured

For an acute exposure (intense but over only a short interval) to have a causal association with subsequent respiratory disease conditions, must the exposure cause acute irreversible and progressive damage evidence by acute clinical illness or, at minimum, objective changes in lung parameters or severe subjective symptoms?

Alternative Broadly Structured

For an acute exposure (intense but over only a short interval) to have a causal association with subsequent respiratory disease conditions, either the exposure must cause acute irreversible (and possibly progressive) damage with or without clinical evidence of the damage, or it must result in or lead to an alteration in individual risk factors which changes the impact of subsequent exposures (e.g., dust exposures, air pollution, cigarette smoking, other environmental agents, respiratory infections).

THE RESPIRATORY END POINTS

This review of respiratory tract responses to a variety of different types of environmental agents has shown that a range of respiratory effects is possible in response to each of the different types of irritant



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