fiber carcinogenesis, including the reasons why hamsters are prone to developing pleural mesotheliomas but not lung tumors after chronic inhalation but rats are more likely to develop lung tumors and have a lower incidence of mesotheliomas. These studies should provide data to help determine the rodent species that are most appropriate for use in human-health risk assessment after exposures to fibers.

Bioassays for lung tumors after inhalation of fibers are based on expensive and time-consuming 2-year carcinogenicity studies. Although the intracavitary-exposure tests might cost less and produce a high incidence of mesotheliomas, they have substantial shortcomings, as discussed in Chapter 5. Consequently, the subcommittee notes that results of intracavitary exposure studies should not be used for purposes of risk assessment. Thus, there is a need for the development and validation of short-term assays to predict long-term effects. These predictive short-term tests could include inhalation and possibly in vitro studies once the mechanisms of fiber carcinogenicity are more fully understood. For any short-term test to be accepted, it must be properly validated against the results of chronic-inhalation studies.

Animal studies of the effects of chronic inhalation of MVF have used mainly particular animal species and fiber types. However, variation in sensitivity among species and dependence of response on fiber type and dimensions are evident. More systematic testing would clarify the patterns of species and fiber-type dependence and aid in the generalization of effects and application to human risk assessment. One such assessment has already been conducted to determine whether a glass-fiber insulation product required a cancer warning label under California proposition 65 (Fayerweather et al. 1997).

Dosimetry studies in animals are needed to clarify the nature and degree of deposition of fibers of various dimensions in different parts of the respiratory tract. Dosimetry studies should also examine the rates of translocation of deposited fibers and the rates at which fibers are dissolved or otherwise cleared; dissolution and cleaving change the magnitude and size distribution of local tissue burdens over time. Studies are needed to clarify how differences in those morphological processes result in variations in sensitivity among species. Methods for defining toxicologically equivalent exposures and tissue burdens across species are needed, and the application of these methods in extrapolating from animal results to humans should be assessed.

The biological mechanisms by which fibers induce tumors and nonma



The National Academies | 500 Fifth St. N.W. | Washington, D.C. 20001
Copyright © National Academy of Sciences. All rights reserved.
Terms of Use and Privacy Statement