8

INFORMATION GAPS AND RECOMMENDATIONS FOR FUTURE RESEARCH

AS is evident from the number of recent studies cited in this report, a considerable amount of research has been and is being conducted in North America and Europe to elucidate the health effects of exposure to manufactured vitreous fibers (MVF). Although much of the research might address the information gaps discussed below, the need for and direction of future research must nonetheless be emphasized.

A recent agreement between the Occupational Safety and Health Administration and manufacturers and users of MVF to monitor exposures of production workers and users, might provide important data for future epidemiological studies (NAIMA 1999). Results of recent life-cycle studies on refractory ceramic fibers (RCF) as used in consumer products (Venturin et al. 1997) are an excellent starting point for this type of study. Monitoring information will be particularly valuable in light of the sparse epidemiological data on special-purpose fibers and other MVF, especially fibers that have been thermally aged. Ideally, monitoring will yield much-needed data on exposures of women and members of racial and other ethnic minorities to MVF. Nested case-control studies that obtain information on potential confounders, such as smoking, could be the best means of addressing questions on the effects of exposures to MVF.

The extrapolation of risks of lung tumors in rats after chronic inhalation of fibers is based on the assumption that the sensitivity of rats to fiber-induced carcinogenesis is similar to that of humans. Potential differences in target-cell sensitivity between rats and humans and the impact of these differences on risk models need to be addressed in future research. The research should focus on elucidating the mechanisms of



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Review of the U.S. Navy's Exposure Standard for Manufactured Vitreous Fibers 8 INFORMATION GAPS AND RECOMMENDATIONS FOR FUTURE RESEARCH AS is evident from the number of recent studies cited in this report, a considerable amount of research has been and is being conducted in North America and Europe to elucidate the health effects of exposure to manufactured vitreous fibers (MVF). Although much of the research might address the information gaps discussed below, the need for and direction of future research must nonetheless be emphasized. A recent agreement between the Occupational Safety and Health Administration and manufacturers and users of MVF to monitor exposures of production workers and users, might provide important data for future epidemiological studies (NAIMA 1999). Results of recent life-cycle studies on refractory ceramic fibers (RCF) as used in consumer products (Venturin et al. 1997) are an excellent starting point for this type of study. Monitoring information will be particularly valuable in light of the sparse epidemiological data on special-purpose fibers and other MVF, especially fibers that have been thermally aged. Ideally, monitoring will yield much-needed data on exposures of women and members of racial and other ethnic minorities to MVF. Nested case-control studies that obtain information on potential confounders, such as smoking, could be the best means of addressing questions on the effects of exposures to MVF. The extrapolation of risks of lung tumors in rats after chronic inhalation of fibers is based on the assumption that the sensitivity of rats to fiber-induced carcinogenesis is similar to that of humans. Potential differences in target-cell sensitivity between rats and humans and the impact of these differences on risk models need to be addressed in future research. The research should focus on elucidating the mechanisms of

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Review of the U.S. Navy's Exposure Standard for Manufactured Vitreous Fibers 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

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Review of the U.S. Navy's Exposure Standard for Manufactured Vitreous Fibers lignant pulmonary dysfunction need to be further investigated. In particular, factors that can influence the shape of the dose-response relationship and could help to identify exposures below which key biological responses are not to be expected, need to be identified. The effects of continuous versus intermittent exposures should also be examined. In general, methods and data appropriate for pursuing quantitative analysis of potential risks of chronic disease from MVF inhalation are needed. Quantitative risk analysis based on epidemiological data is hampered by the limited quantitative information on dosimetry. Epidemiology studies that incorporate measurements of fiber exposures or that reconstruct estimates of worker exposures to fibers, over the last several decades would aid in this endeavor. The use of MVF as insulation material means that they are subjected to variations in temperature. Heat stress can result in changes in fibers' chemical and physical structure. However, there is a lack of information on the effect of heat stress on fiber structure and fiber breakdown. Such information could be important for assessing the exposures of Navy personnel and other workers to MVF. The toxicity of heat-stressed MVF—particularly those produced to withstand high temperature, such as RCF—has yet to be fully explored. Pursuit of a research agenda as suggested above poses formidable challenges. It will need to be a continuing process that is not the province solely of the Navy, but rather of the fiber research community in general. Although monitoring data might always be difficult to come by, it is imperative that the Navy determine the concentrations and characteristics (such as, fiber length, diameter, and composition) of the MVF, particularly RCF, to which its personnel are exposed. That could be accomplished by air monitoring or by an inventory of the fiber content of the MVF-containing equipment and materials used by the Navy. The subcommittee believes that when the Navy adopts another organization 's standard, as it has adopted the American Conference of Governmental Industrial Hygienists threshold limit value, it must evaluate the rationale used by the other organization to develop the standard so that it can assess how appropriate the standard is for its own purposes. It is important that typical fiber concentrations and exposure ranges be measured in the workplace air so that actual worker exposure can be compared with established or proposed occupational exposure standards. Such data and comparisons are necessary for any quantitative risk assess

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Review of the U.S. Navy's Exposure Standard for Manufactured Vitreous Fibers ment and its accompanying uncertainty analysis. The Navy might also want to consider asking its suppliers to provide, where possible, materials that use low-biopersistence MVF. The Navy should regard its current occupational standard as only one point on an ever-changing mosaic of exposure standards that will require periodic adjustments as new toxicological data become available, new monitoring studies are conducted, and new MVF are introduced into the workplace.