Evaluation of Short-Term Bioassays to Predict Functional Impairment. Selected Short-Term Pulmonary Toxicity Tests

摘要

The MITRE Corporation has been requested by the U.S. Army Medical Bioengineering Research and Development Laboratory to identify and evaluate short-term bioassays which have demonstrated ability to assess and predict impairment of the pulmonary system resulting from exposure to chemicals. This document reviews the literature on test procedures for determining toxic effects on the lungs and other components of the pulmonary system. The procedures are discussed in sections on morphology, respiratory mechanics, gas exchange, circulation, defense mechanisms and biochemistry. The evaluation criteria that have been used in assessing the test procedures are the test's state of development and whether it (1) has been performed in small animals and conscious animals; (2) is terminal; (3) is sensitive, accurate and reproducible; and (4) is relatively easy to perform. The tests that satisfy these criteria are compliance and resistance tests, lung volume and capacity tests, the distribution of ventilation by nitrogen washout test, arterial blood gas measurements and the carbon monoxide diffusing capacity test. Several other tests merit consideration for use specific screening programs but do not satisfy all the selection criteria. Some tests are not currently recommended for a pulmonary toxicity screening program. (Author)