defenses, and the single dose (or a few repeated doses) is not physiologically based and can create an overload in the peritoneal or pleural cavity. Intracavitary tests can also yield false-positive results, for the assessment of lung cancer and mesothelioma risks. The WHO consultation (WHO 1992) concluded that the intracavitary model should not be used for quantitative risk assessment or for hazard evaluation of fibers.

Of the three types of tests that can be used to screen for fiber toxicity—inhalation, instillation, and intracavitary—one might be more advantageous than another. Intracavitary tests are not recommended because of the numerous deficiencies discussed above. Results of instillation studies are qualitatively similar to those of inhalation studies (Henderson et al. 1995) and are adequate for short-term estimates of toxicity and fiber-clearance studies, but they cannot substitute for inhalation models for setting dose levels. Short-term inhalation testing should be used for estimating toxicity, evaluating mechanisms, and setting doses for subchronic or chronic inhalation studies. With regard to the latter goal, it is likely that the data generated from short-term inhalation tests could be used to set dose levels for 90-day inhalation studies, thus obviating costly 2-week or 28-day dose-setting inhalation studies.



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