3
Major Scientific Issues: State of the Science and Future Research Directions

The NIOSH Roadmap (NIOSH, 2009) proposes a set of studies to improve knowledge on the potential health effects of elongate mineral particles and the ways in which human exposures can best be studied. The proposed studies are founded upon a broad span of scientific literature on these topics that has been well summarized in the draft Roadmap. This chapter provides the committee’s review of the major scientific issues discussed in the Roadmap.

TERMINOLOGY AND NOMENCLATURE

The NIOSH Roadmap devotes considerable attention to mineralogical terminology and nomenclature. In the last several years it has become increasingly clear that the terminology historically used to describe asbestos in workplace or environmental exposures is inadequate and is often applied incorrectly or inconsistently. Examples include minerals not currently listed in regulatory language, such as winchite and richterite asbestos. This is not to say that the proper mineralogical terminology does not exist. Rather, the terminology used by mineralogists is very specific and covers the full range of minerals and properties that are identified for study in the NIOSH Roadmap, but this terminology is not consistently applied in the Roadmap document. One problem is that mineralogical terminology has frequently been misinterpreted in the scientific literature, commercial publications, and regulatory language, resulting in confusion regarding the exact meaning of mineralogical terms, including those used in describing the physical characteristics of minerals.



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3 Major Scientific Issues: State of the Science and Future Research Directions The NIOSH Roadmap (NIOSH, 2009) proposes a set of studies to improve knowledge on the potential health effects of elongate mineral particles and the ways in which human exposures can best be studied. The proposed studies are founded upon a broad span of scientific litera- ture on these topics that has been well summarized in the draft Roadmap. This chapter provides the committee’s review of the major scientific is- sues discussed in the Roadmap. TERMINOLOGY AND NOMENCLATURE The NIOSH Roadmap devotes considerable attention to mineralogi- cal terminology and nomenclature. In the last several years it has become increasingly clear that the terminology historically used to describe as- bestos in workplace or environmental exposures is inadequate and is of- ten applied incorrectly or inconsistently. Examples include minerals not currently listed in regulatory language, such as winchite and richterite asbestos. This is not to say that the proper mineralogical terminology does not exist. Rather, the terminology used by mineralogists is very spe- cific and covers the full range of minerals and properties that are identi- fied for study in the NIOSH Roadmap, but this terminology is not consistently applied in the Roadmap document. One problem is that min- eralogical terminology has frequently been misinterpreted in the scien- tific literature, commercial publications, and regulatory language, resulting in confusion regarding the exact meaning of mineralogical terms, including those used in describing the physical characteristics of minerals. 33

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34 REVIEW OF THE NIOSH ROADMAP The Roadmap includes a glossary to attempt to clarify for the reader the ambiguities in meanings and concepts. However, the glossary pres- ently contains many words that are not scientifically or technically valid, as well as definitions of scientific terms that are incorrect or need greater detail. 1 The committee emphasizes the need to establish and maintain scientific rigor in the glossary definitions and use of terminology in the Roadmap. The committee strongly endorses the use of correct minera- logical terminology and believes that using accepted and scientifically rigorous terminology and nomenclature throughout the Roadmap, includ- ing the Roadmap glossary and in subsequent research activities, is the best means to ensure an accurate understanding of proposed research directions and, ultimately, research outcomes. A complementary goal is that this rigor in terminology may eventually be applied consistently in the regulatory setting. In creating a new acceptable paradigm for risk assessment in this area, the Roadmap should not continue the historical use of ambiguous terminology occasionally found in some existing stan- dards and guidelines. To ensure proper scientific terms, a modern techni- cal glossary or other standard reference text, appropriate for the field of study, should be used and cited. For example, the American Geological Institute Glossary of Geology may be appropriate for many of the min- eralogical or geological terms (Neuendorf et al., 2005). Other reference texts should be consulted for words not found in the AGI glossary or for toxicological or epidemiological terms. Words or terms that are not sci- entifically or technically valid should be removed from the glossary and the text. NIOSH has also recognized a problem with or deficiency in existing terminology that has caused confusion and concern for researchers, pol- icy makers, and others involved in these issues. NIOSH has introduced the term elongated mineral particle to encompass the broad range of mineral particles that are the primary focus of the proposed research. The committee urges the use of the descriptive term elongate, rather than elongated so as to describe the physical appearance of the particles as opposed to implying that they have been actively lengthened (see also 1 Suggestions for terms that need well-referenced definitions include acicular, actino- lite, amphibole, anthophyllite, asbestiform, asbestos, chrysotile, cleavage fragment, cro- cidolite, fiber, fibril, fibrous, solid solution series, and tremolite. Note that the terms asbestiform and asbestos are not equivalent to fibrous or fiber; nonasbestiform minerals and synthetic materials can also be fibrous. Suggestions for terms to consider removing from the glossary include countable particle, covered mineral, and fragility. Terms to consider adding to the glossary include crystal and petrographic thin section.

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35 MAJOR SCIENTIFIC ISSUES Chapter 1). The committee does not believe that the acronym EMP should be used. Use of the acronym could impart more rigor and homo- geneity to a term that actually describes a diverse group of mineral parti- cles of a certain length and aspect ratio. An elongate mineral particle is defined as “any fiber or fragment of a mineral longer than 5 μm with a minimum aspect ratio of 3:1 when viewed microscopically using NIOSH Analytical Method #7400 (‘A’ rules) or its equivalent” (NIOSH, 2009, p. 61). This term as introduced in the Roadmap is all-encompassing and includes not only asbestos and nonasbestiform mineral particles but also those minerals or particles that are defined, for example, as acicular or prismatic or as cleavage frag- ments. Nonetheless, the committee considers the dimensions described in the definition (“longer than 5 μm with a minimum aspect ratio of 3:1”) as a good starting point for research since this encompasses the respirable size range. The committee believes that as knowledge of these mineral particles and their potential for health effects accumulates, the definition of these dimensions should be periodically revisited and refined with the goal of providing a more evidence-based justification. However, this definition used by NIOSH also applies to non-respirable mineral parti- cles as it does not place an upper bound on diameter. For example, a fi- ber with a diameter of 6 μm and an aspect ratio of 3:1 would likely not be respirable but would be counted under the 7400A rules. While this may not be a problem with most traditional asbestos samples, as more elongate particles are evaluated, this lack of differentiation may prove problematic. Additionally, while this definition has been adopted by NIOSH in rulemaking, it is not consistent with other recognized fiber counting schemes such as the World Health Organization method which does place an upper bound on fiber diameter as do the NIOSH 7400B counting rules. It is also important for the Roadmap to acknowledge that the term elongate mineral particle is not a rigorous mineralogical classi- fication or one to which regulatory significance is assigned, but rather serves a useful purpose in encompassing the full continuum of minerals from asbestiform through nonasbestiform, within specified dimensions. As such, the term elongate mineral particle is a convenient, neutral, and uniform means for the disciplines of mineralogy, toxicology, and epide- miology to discuss broad categories of mineral particles with potentially widely varying potency for causing cancer and other health effects. In the NIOSH Roadmap and in this report, the focus is on minerals, which are naturally occurring substances; discussions of research on synthetic materials are included to provide examples of potential research direc-

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36 REVIEW OF THE NIOSH ROADMAP tions or to provide information within the broader context of airborne particulates. Regarding other terminology issues, the committee highlights a few terms in this chapter that require attention. The term asbestos is a com- mercial term generally referring to the Occupational Safety and Health Administration (OSHA) and Mine Safety and Health Administration (MSHA) regulatory definitions that specify six minerals: chrysotile, cummingtonite-grunerite asbestos (commercially termed amosite), an- thophyllite asbestos, riebeckite asbestos (crocidolite), tremolite asbestos, and actinolite asbestos (29 CFR 1910.1001(b); 29 CFR 1926.1101(b); 30 CFR 56.5001(b)(1); 30 CFR 57.5001(b)(1); 30 CFR 71.702(a); Ampian, 1976). Other authors have used the term more broadly to include miner- als that occur in the asbestiform habit, but usage is usually restricted to minerals of the amphibole group and the mineral chrysotile (Lowers and Meeker, 2002). Importantly, nonasbestiform analogs of these six miner- als also exist and often occur in similar sizes and shapes as specified in the various regulations and definitions. The term cleavage fragment, a fragment of a crystal that is bounded by cleavage faces (Neuendorf et al., 2005), has often been used incor- rectly in describing both asbestos and nonasbestiform analogs. This is significant because several toxicity studies appear to suggest that cleav- age fragments, which are not regulated currently by OSHA or MSHA, are less toxic than asbestiform particles of the same mineral (Addison and McConnell, 2008). While more research is needed to address this issue, the existing research does not support extending these findings beyond cleavage fragments to the broader class of prismatic to fibrous particles. Conversely, the term asbestos has often been used inappropri- ately to describe any particle that meets the counting criteria of a particu- lar analytical method (e.g., 3:1 aspect ratio and greater than 5 μm length). The potential health effects of some nonasbestiform mineral particles have not been studied, and the potency of respirable prismatic, acicular, and fibrous particles that do not meet the definitions of commercial as- bestos is not known. NIOSH has identified in the Roadmap some re- search that may help to clarify these issues and to resolve questions now being debated. Another consideration with regard to terminology is the naming or identification of specific minerals. Mineral names in the geological community are endorsed by the International Mineralogical Association (IMA) Commission on New Minerals, Nomenclature, and Classification (CNMNC), which is charged with approving, defining, and occasionally

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37 MAJOR SCIENTIFIC ISSUES redefining or reassigning mineral names (IMA, 2009). The CNMNC rec- ognizes that its nomenclature serves only as a recommendation to the mineralogical community (Nickel and Grice, 1998). Although the IMA nomenclature is accepted by the primary mineralogical research journals, and therefore its use is generally required for publication in those jour- nals, the IMA nomenclature carries no actual statutory authority in the United States. An issue encountered in the application of IMA terminology to as- bestos outside the mineralogical community is that the IMA CNMNC continues to refine and redefine mineral names for mineralogical re- search purposes based on new data and understanding of minerals. An example is the redefinition of amphibole names by the IMA Committee on Amphibole Nomenclature, which has revised the amphibole nomen- clature three times since 1978. An additional proposal for another major reorganization of amphibole nomenclature has recently been proposed to the mineralogical community (Hawthorne and Oberti, 2007). These changes in mineral names far outpace the ability of the rulemaking and legislative processes in the United States and have caused considerable confusion and misunderstanding, as is evident in recent legal actions re- lating to asbestos contamination in Libby, Montana. Finally, the correct application of IMA amphibole nomenclature (Leake et al., 1997, 2004) requires analytical precision and accuracy that is generally beyond the capability of the standard asbestos analysis methods used for exposure assessment purposes. This presents difficulties for the comparison of analytical results between, and even within, laboratories. Within the chemical community, the Chemical Abstracts Service (CAS) Registry provides definitions of chemical substances including asbestos. Unlike the IMA, the CAS Registry does carry some statutory authority. However, CAS Registry definitions can often be vague. An example is the general definition of asbestos (CAS 1332-21-4) from the online Chemical Abstracts Registry database as “a grayish, noncombus- tible fibrous material” consisting “primarily of impure magnesium sili- cate minerals”—a definition that could apply to several hundred silicate minerals. The CAS definition for asbestos was ruled applicable by the U.S. Ninth Circuit Court of Appeals for the Clean Air Act (U.S. Court of Appeals, 2007). This dichotomy between the generally precise IMA definitions and the less detailed and less precise CAS definitions presents significant difficulties for those involved in work on asbestos and other elongate minerals.

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38 REVIEW OF THE NIOSH ROADMAP The committee believes that the rigor of established mineralogical terminology is critical to the research process and the ultimate under- standing of the mechanisms of toxicity. Therefore, the committee sug- gests that the Roadmap remain consistent in its use of referenced mineralogical nomenclature rather than commercial names (e.g., amosite). It must also be recognized that mineralogical definitions and nomenclature have changed and may change in the future. It is therefore important that the specific mineral nomenclature scheme used in any publications, such as the Leake et al. (1997, 2004) nomenclature for am- phiboles, always be referenced so as to make clear the specific defini- tions being applied. Issues of terminology also arise in other relevant research disci- plines. The problem of the incorrect use and corruption of terminology extends beyond the question of misunderstanding and unintentional mis- use in that it provides an opportunity for exploitation of the terminology to achieve an expedient outcome. It is therefore extremely important that researchers, policy makers, regulatory staff, and others working on these issues take great care in using terminology that is precise and fully de- veloped so that the intent is totally clear. Clear and consistent use of con- ventional terminology in the Roadmap is thus essential. With the terminology considerations suggested above, this chapter subsequently highlights a mineral characterization scheme for establish- ing and using mineral standards that have been well-characterized physi- cally and chemically for use in toxicological research. MINERAL CHARACTERIZATION AND STANDARDIZED REFERENCE MINERALS Mineralogy is a fundamental science relating an enormous number of naturally occurring solid materials. A robust, systematic classification scheme for minerals exists based on rigid compositional and structural (crystallographic) criteria. These criteria are well defined and can be quantified. The Roadmap would benefit from further emphasis on the mineralogical research needed and from discussion of the development of standardized reference mineral samples that could be used in toxico- logical studies to assess the variability in the toxicity of different types of elongate mineral particles. Major issues faced in research in this area include (1) that the bulk rock or ore may contain a complex suite of min- erals and that this complexity, although relevant to the toxicological

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39 MAJOR SCIENTIFIC ISSUES properties of the dust, may not be detectable in the respirable dust de- rived from the bulk because of analytical limitations, (2) the relative per- centage of different minerals present, and (3) the physical characteristics, which may vary with the size fraction after attrition. For these reasons, characterizing the fundamental properties of elongate mineral particles is essential. Mineral Characterization Minerals have fundamental properties that can be defined in terms of physical (e.g., growth habit, hardness, cleavage), chemical (e.g., chemi- cal composition, surface reactivity, solubility), optical (e.g., translucence, refractive indices), and electrical (e.g., conductivity, resistivity) charac- teristics, among others. A degree of variability in the compositional and structural makeup of specific minerals in nature also exists, reflecting differences in petrogenesis and mineral source (natural conditions of formation). Therefore, minerals exhibit a range of physical and chemical properties that result in varied responses to conditions imposed during extraction, processing, and experimentation. Research on the degree of variability between mineral species and within mineral groups, due to their natural conditions of formation, and the extent to which these vary- ing characteristics influence toxicity is largely absent from the Roadmap and more detail is needed. Key variables of relevance in studying minerals include surface crys- tal structure and chemistry, size and shape characteristics, and mineral habit—all of which will vary depending on the composition, environ- ment of growth, and response to physical and chemical processing of mineral samples. Essential to the consistent rigorous characterization of minerals is the consideration of mineralogical properties in a similar way throughout the mineral “life cycle”—from extraction or liberation at the source to processing for use in manufactured products or as research ma- terials. Modern methods of mineral characterization can also provide a statistical representation of the range of minerals and their physical char- acteristics. This form of minerals characterization is used routinely by the mineral industry to identify and quantify mineral samples in terms of their variability in composition, size, and shape. Whether establishing a new reference mineral sample for eventual use in health-related research or characterizing an unknown suite of elongate mineral particles from an air sample filter, a basic set of mineral

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40 REVIEW OF THE NIOSH ROADMAP characterization techniques can be employed in a tiered fashion. Addi- tional characterization techniques can then be employed if required. The level of analytical detail will depend upon the goal of the research. Table 3-1 outlines a basic characterization sequence and suggests potential out- comes of the research that can be used to plan further research in a sys- tematic way. Such an approach to mineral characterization is currently absent from the Roadmap. The committee believes that a fundamental problem with the pro- posed research in the Roadmap is the reliance on limited and outdated analytical methods such as phase contrast microscopy (PCM). Other methods such as transmission electron microscopy (TEM) or scanning electron microscopy (SEM) are not recommended for use exclusively or as “stand-alone” analytical methods. Rather, TEM or SEM can be used most effectively in conjunction, if possible, with the petrographic tech- niques listed in Table 3-1. The need to develop new methods based on electron microbeam analysis techniques is critical and should not be lim- ited by existing regulatory constraints or existing policy. The committee strongly believes that the science should drive the policy and regulation, not the reverse. Prediction and prevention are linked to having well-characterized sample sets for experimental work and analysis. The Roadmap recog- nizes that workers may be exposed to any number of crushed and ground and/or contaminant particles introduced during mining, milling, manu- facturing, and demolition of the materials. In these cases, the size and shape criteria used to describe elongate mineral particles encompass many mineral groups in addition to asbestos and analogous minerals. Mineral source and petrogenetic studies can be used to help characterize mineralogical materials in terms of source (original geological source for the mineral and formation conditions). By using statistically reasonable sample populations from diverse natural sources and rock localities (e.g., mines), including historical data sets, minerals from an air sample filter may be classified not only by mineral composition, optical properties, size, and shape, but also by petrogenetic history. This type of approach also has the potential to aid in the design of tailored toxicological studies linked specifically to a particular mineral source and could provide pre- dictive assessment for materials derived from similar geological settings.

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41 MAJOR SCIENTIFIC ISSUES TABLE 3-1 Tiered Approach to Mineral Characterization Characterization Step Purpose Further Application 1. Examine original Establishes mineral This step creates the ini- rock from source characteristics, min- tial data set of relevant and determine eral chemical varia- mineralogy and minera- mineral content, tions, basic growth logical associations that mineral habits, habit of single crystals will be further developed textures, and chem- and aggregates of through subsequent istry in situ (petro- minerals (e.g., equant, stages. graphic analysis of granular, acicular, thin sections and radiated growth hab- hand specimen its). Yields a quantita- analysis [polarized tive appreciation of light microscopy, the distribution of PLM]; electron minerals in situ and probe microanalysis their growth relation- [EPMA]). ships. Note that cleav- age fragments are fragments of single crystals and are not regulated by MSHA and OSHA. 2. Comminute the Establishes the range This step identifies and sample to different, of habits—from fi- refines the list of relevant relevant size frac- brous to acicular to criteria related to poten- tions and character- prismatic, etc.—that tial health impacts. ize the minerals may be present in a optically in terms of mixed mineral sample shape, habit, texture, that has undergone size, and chemistry various degrees of using optical miner- processing and the alogy and/or elec- degree to which spe- tron beam cific minerals may techniques. These persist through greater characteristics may levels of processing. also be applied to an unknown mineral set from an air sam- ple filter. Continued

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42 REVIEW OF THE NIOSH ROADMAP TABLE 3-1 Continued Characterization Step Purpose Further Application 3. Analyze the thin In combination with Mineralogically charac- sections, or crushed PLM, SEM provides terized samples can be samples, in con- an option for larger used further in controlled trolled size fractions data sets that are more toxicological research. by EPMA, XRD, representative of the XRF, PLM, SEM, sample population. and TEM. TEM measurements can provide diffraction information to help distinguish the crystal- lographic differences among various asbes- tos minerals. New technologies in quanti- tative mineralogy and image analysis aid with size distribution and counting statistics. 4. Detailed analysis of Methods include Further understanding of individual grains, EXAFS, Auger, AFM, the surface characteristics such as that offered Mössbauer spectros- of specific grain popula- by surface analysis copy, EBSD, synchro- tions can be useful for provides informa- tron, and three- toxicological studies of tion on oxidation- dimensional analysis human tissue and fluids. reduction state, elec- combined with knowl- trostatic behavior, edge of biodurability and other potentially and length of resi- relevant properties. dency of particles with specific charac- teristics. NOTES: AFM = atomic force microscopy; EBSD = electron backscattered diffraction; EPMA = electron probe microanalysis; EXAFS = extended X-ray absorption fine struc- ture; PLM = polarized light microscopy; SEM = scanning electron microscopy; TEM = transmission electron microscopy; XRD = X-ray diffraction; XRF = X-ray fluorescence. When analyzing natural materials for basic mineralogical research and characterization, data from steps 1 and 2 are required, whether from historical sources or newly collected by the analyst. Steps 3 and 4 involve progressively more sophisticated types of analysis for mineralogical and, eventually, toxicological research purposes. For rapid identifica- tion and characterization of unknown samples from worker air sample filters for regula- tory purposes, steps 2 and 3 are the relevant actions to employ.

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43 MAJOR SCIENTIFIC ISSUES Research is also needed into the potentially toxicological responses of exposure to mixtures of elongate mineral particles. The complexities of this research underscore the need to have well-characterized mineral samples in the context of their natural sources and petrogenesis in order to understand the controlling variables in the toxicological experiments. Standardized Reference Minerals Well-characterized reference mineral samples are important for re- search on the potential health effects of elongate mineral particles, and the need for a well-managed repository should be emphasized. The iden- tification, classification, and characterization of unknown mineral parti- cles from workplace or environmental exposures require comparison to rock-forming minerals that have been characterized mineralogically by conventional petrographic techniques. Similarly, designing and conduct- ing meaningful toxicological experiments require well-characterized ref- erence mineral samples to allow systematic intra- and interlaboratory comparisons of results. The Roadmap notes the need for standardized reference mineral samples but should include more details on an ap- proach to developing a central repository for systematically characteriz- ing and standardizing the samples. This type of repository provides better precursor material for research of the sort proposed in the Roadmap. Ideally, all minerals studied by laboratory inhalation exposures should either be obtained from the repository or be matched with smaller samples that are well characterized and included in the repository. It should be noted that substantial quantities of minerals would be neces- sary if the repository intends to support long-term whole-body inhalation studies. (Smaller quantities are needed for nose-only inhalation studies.) For example, tens of kilograms of respirable minerals would be required to conduct a multi-dose inhalation study of sufficient magnitude to test carcinogenic potential. This does not obviate the need for a repository of smaller samples of standardized minerals. A few grams could support comparative in vitro tests that would help place the effects of inhaled minerals into context, even if the study sample did not come from the repository. Several sets of standardized reference minerals have been developed in laboratories of the National Institute of Environmental Health Sciences (NIEHS) and the former U.S. Bureau of Mines (USBM), as well as other groups, and could be included in a central repository.

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66 REVIEW OF THE NIOSH ROADMAP Counting Strategies In reviewing the literature on asbestos counting, there appears to be considerable variability in counts from analyst to analyst within a given laboratory as well as between laboratories. As a consequence, a new ob- served count from a particular analyst from a particular laboratory may deviate considerably from the true value. In an effort to provide a con- nection between observed and true counts and characterize the uncer- tainty in the true count, Dulal Bhaumik and colleagues have extended the ideas of Gibbons and Bhaumik (2001) and Bhaumik and Gibbons (2005) to the case of a Poisson random variable, which is the appropriate distri- bution for rare-event count data. Appendix B provides a brief sketch of one potential methodology for addressing the variability as well as an illustration of the application of this methodology. Statisticians who are also familiar with exposure data analysis should be actively involved in addressing some of the challenging data analysis issues in this area of research. Additional Statistical Issues There is considerable discussion in the NIOSH Roadmap on the ef- fect of fiber counts and fiber dimensions on exposure risk. Thus the dis- tribution of these quantities is of obvious interest. For exposure assessment, it is important to characterize the joint distribution of fiber length and width for a given material. Several researchers (see Cheng, 1986; Baron, 2001; Cheng et al., 2006) have investigated this problem and noticed that fiber length and width typically have a bivariate log- normal distribution. Data analysis based on the bivariate lognormal dis- tribution can be complicated, depending on the parameter or parameters for which inference is desired. Likelihood based results for testing or constructing confidence intervals for one or more parameters of the dis- tribution often produce undesirable results (e.g., inflated type 1 error rates or low coverage probability) when sample sizes are small. In order to overcome this problem one can explore procedures based on the novel concepts of generalized p-values (for hypothesis testing) and generalized confidence intervals (for computing confidence intervals) for univariate and bivariate lognormal distributions (see Krishnamoorthy and Mathew, 2003; Krishnamoorthy et al., 2006; Bebu and Mathew, 2008). Major ad- vantages of such procedures are that they are accurate and are applicable

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67 MAJOR SCIENTIFIC ISSUES to small samples. The concepts of generalized p-values and generalized confidence intervals also provide accurate methodology for comparing two lognormal distributions (for example, to compare the arithmetic means of fiber lengths obtained from two different sites or materials). The NIOSH Roadmap also addresses the issue of comparing thoracic samplers. To compare thoracic samplers, the OSHA criterion for estab- lishing the equivalence of a sampling device to a reference device re- quires that “90 percent of the readings of the sampling device should be within plus or minus 25 percent of the readings obtained by the reference device, or within plus or minus 25 percent of the actual airborne chemi- cal concentration.” In this context one can use rigorous statistical tests developed by Krishnamoorthy and Mathew (2002) for comparing two samplers, and Krishnamoorthy et al. (2009) for comparing several sam- plers. The OSHA criterion, or a suitable version of it, appears to be the right criterion to compare thoracic samplers. Traditional approaches for comparison of samplers based on geometric means using t-tests are gen- erally inadequate. SPECIFIC COMMENTS In addition to the major issues discussed throughout this chapter, the following paragraphs highlight a few specific suggestions for considera- tion to improve the Roadmap. Some minor changes to the front matter might help readers under- stand the full context of the report and the iterations it has gone through. This could include detailing the specific drafts and dates of the drafts and pointing out that the peer reviewers listed on page xii reviewed the Feb- ruary 2007 draft. A timeline (see Table 2-1 of this report) may be helpful since the Roadmap has undergone several iterations. The committee also believes that the goal of the document should be reflected in the title and the cover. If the research is intended to address all elongate mineral particles, not just asbestos or its analogs, a different title might be appro- priate. If the Roadmap is expanded at some point to include a larger range of elongate particles, more generally (whether minerals, man-made materials [e.g., ceramics], organic materials [e.g., wool and cotton], or others), the title should reflect that intent. Given the broad spectrum of elongate mineral particles addressed in the Roadmap, the cover photo- graphs and design should also reflect this wide range of particles with

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68 REVIEW OF THE NIOSH ROADMAP captions that are informative regarding the scale bars, labels, and other information. Care should be taken to ensure that descriptions of studies written prior to the release of the Roadmap use the same terminology used in the original article. If necessary, a note could be added to clarify or update the terminology. Because elongate mineral particle is a broad descriptive term and not a rigorous mineralogical term, the preference when feasible is for providing the correct mineral names. REFERENCES Addison, J., and E. E. McConnell. 2008. A review of carcinogenicity studies of asbestos and non-asbestos tremolite and other amphiboles. Regulatory Toxicology and Pharmacology 52(Suppl 1):S187–S199. Amandus, H. E., and R. Wheeler. 1987. The morbidity and mortality of vermiculite miners and millers exposed to tremolite–actinolite: Part II. Mortality. American Journal of Industrial Medicine 11:15–26. Ampian, S. G. 1976. Asbestos minerals and their nonasbestos analogs. Presentation to the Mineral Fibers Session, Electron Microscopy of Microfibers. Pennsylvania Sate University, August 23–25. ATSDR (Agency for Toxic Substances and Disease Registry). 2008. B iomarkers of asbestos exposure and disease . http://www. atsdr.cdc.gov/asbestos/asbestos/biomarkers_asbestos/index.html (ac- cessed September 9, 2009). Baron, P. A. 2001. Measurement of airborne fibers: A review. Industrial Health 39:39–50. Bebu, I., and T. Mathew. 2008. Comparing the means and variances of a bivariate lognormal distribution. Statistics in Medicine 14:2684– 2696. Berman, D. W., K. S. Crump, E. J. Chatfield, J. M. Davis, and A. D. Jones. 1995. The sizes, shapes, and mineralogy of asbestos structures that induce lung tumors or mesothelioma in AF/HAN rats following inhalation. Risk Analysis 15(2):181–195. Bernstein, D. M., and J. A. Hoskins. 2006. The health effects of chry- sotile: Current perspective based on recent data. Regulatory Toxicol- ogy and Pharmacology 45(3):252–264. Bernstein, D. M., R. Rogers, P. Smith, and J. Chevalier. 2006. The toxicological response of Brazilian asbestos: A multidose subchronic 90-day inhalation toxicology study with 92-day recovery to assess

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69 MAJOR SCIENTIFIC ISSUES cellular and pathological response. Inhalation Toxicology 18(5):313– 332. Bertino, P., A. Marconi, L. Palumbo, B. M. Bruni, D. Barbone, S. Germano, A. U. Dogan, G. F. Tassi, C. Porta, L. Mutti, G. Gaudino. 2007. Erionite and asbestos differently cause transformation of human mesothelial cells. International Journal of Cancer 121(1):12– 20. Bhaumik, D. K., and R. D. Gibbons. 2005. Confidence regions for ran- dom-effects calibration curves with heteroscedastic errors. Technometrics 62:223–230. Bocchetta, M., I. Di Resta, A. Powers, R. Fresco, A. Tosolini, J. R. Testa, H. I. Pass, P. Rizzo, and M. Carbone. 2000. Human mesothe- lial cells are unusually susceptible to simian virus 40-mediated trans- formation and asbestos cocarcinogenicity. Proceedings of the National Academy of Sciences 97(18):10214–10219. Both, K., D. W. Henderson, and D. R. Turner. 1994. Asbestos and erio- nite fibers can induce mutations in human lymphocytes that resulted in loss of heterozygosity. International Journal of Cancer 59:538– 542. Brown, D. P., S. D. Kaplan, R. D. Zumwalde, M. Kaplowitz, and V. E. Archer. 1986. Retrospective cohort mortality study of underground gold mine workers. In Silica, Silicosis, and Lung Cancer, edited by D. Goldsmith, D. Winn, and C. Shy. New York: Praeger. Pp. 335– 350. Brunner, W. M., A. N. Williams, and A. P. Bender. 2008. Investigation of exposures to commercial asbestos in northeastern Minnesota iron miners who developed mesothelioma. Regulatory Toxicology and Pharmacology 52(Suppl 1):S116–S120. Cacciotti P., D. Barbone, C. Porta, D. A. Altomare, J. R. Testa, L. Mutti, and G. Gaudino. 2005. SV40-dependent AKT activity drives meso- thelial cell transformation after asbestos exposure. Cancer Research 65(12):5256–5262. Campbell, W. J., C. W. Huggins, and A. G. Wylie. 1980. Chemical and physical characterization of amosite, chrysotile, crocidolite, and nonfibrous tremolite for oral ingestion studies by the National Insti- tute of Environmental Health Sciences. Washington, DC: U.S. Bu- reau of Mines. R. I. 8452. Cheng, Y-S. 1986. Bivariate lognormal distribution for characterizing asbestos fiber aerosols. Aerosol Science and Technology 5:359–368.

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70 REVIEW OF THE NIOSH ROADMAP Cheng, Y-S., T. D. Holmes, and B. Fan. 2006. Evaluation of respirator filters for asbestos fibers. Journal of Occupational and Environ- mental Hygiene 3:26–35. Christensen, V. R., S. Lund Jensen, M. Guldberg, and O. Kamstrup. 1994. Effect of chemical composition of man-made vitreous fibers on the rate of dissolution in vitro at different pHs. Environmental Health Perspectives 102(Suppl 5):83–86. Cooper, W. C., O. Wong, and R. Graebner. 1988. Mortality of workers in two Minnesota taconite mining and milling operations. Journal of Occupational Medicine 30:506–511. Cooper, W. C., O. Wong, L. S. Trent, F. Harris. 1992. An updated study of taconite miners and millers exposed to silica and nonasbestiform amphiboles. Journal of Occupational Medicine 34:1173–1180. Davis, J. M., J. Addison, C. McIntosh, B. G. Miller, and K. Niven. 1991. Variations in carcinogenicity of tremolite dust samples of differing morphology. Annals of the New York Academy of Sciences 643:473– 490. de Meringo, A., C. Morscheidt, S. Thélohan, and H. Tiesler. 1994. In vitro assessment of biodurability: Acellular systems. Environmental Health Perspectives 102(Suppl 5):47–53. Enterline, P. E., and V. L. Henderson. 1987. Geographic patterns for pleural mesothelioma deaths in the United States, 1968–81. Journal of the National Cancer Institute 79:31–37. European Commission Joint Research Centre. 1999. Methods for the determination of the hazardous properties for human health of man made mineral fibres (MMMF), edited by D. M. Bernstein and J. M. Riego Sintes. http://tsar.jrc.ec.europa.eu/documents/Testing-Methods /mmmfweb.pdf (accessed October 5, 2009). Gibbons, R. D., and D. Bhaumik. 2001. Weighted random-effects regression models with application to inter-laboratory calibration. Technometrics 43:192–198. Gillam, J., J. Dement, R. Lemen, J. Wagoner, V. Archer, and H. Blejer. 1976. Mortality patterns among hard rock gold miners exposed to an asbestiform mineral. Annals of the New York Academy of Sciences 271:336–344. Hawthorne, F. C., and R. Oberti. 2007. Classification of the amphiboles. Reviews in Mineralogy and Geochemistry 67:55–88. Hei, T. K., L. J. Wu, and C. Q. Piao. 1997. Malignant transformation of immortalized human bronchial epithelial cells by asbestos fibers. En- vironmental Health Perspectives 105:1085–1088.

OCR for page 33
71 MAJOR SCIENTIFIC ISSUES Hei, T. K., A. Xu, D. Louie, and Y. L. Zhao. 2000. Genotoxicity versus carcinogenicity: Implications from fiber toxicity studies. Inhalation Toxicology 12:141–147. Hesterberg, T. 2009. Comments on Asbestos Roadmap—Animal Bioas- says. Presentation to the Committee for the Review of the NIOSH Roadmap on Asbestos and Other Elongate Mineral Particles. Wash- ington, DC, March 30. Hesterberg, T. W., and J. C. Barrett. 1984. Dependence of asbestos- and mineral dust-induced transformation of mammalian cells in culture on fiber dimension. Cancer Research 44(5):2170–2180. Hesterberg, T. W., and G. A. Hart. 2001. Synthetic vitreous fibers: A review of toxicology research and its impact on hazards classifica- tion. Critical Reviews of Toxicology 1:1–53. Hesterberg, T. W., G. A. Hart, W. C. Miiller, G. Chase, R. A. Rogers, J. B. Mangum, and J. I. Everitt. 2002. Use of short-term assays to evaluate the potential toxicity of two new biosoluble glasswool fi- bers. Inhalation Toxicology 14:217–246. Higgins, I. T. T., J. H. Glassman, M. S. Oh, and R. G. Cornell. 1983. Mortality of Reserve Mining Company employees in relation to taconite dust exposure. American Journal of Epidemiology 118:710– 719. Hull, M. J., J. L. Abraham, and B. W. Case. 2002. Mesothelioma among workers in asbestiform fiber-bearing talc mines in New York State. Annals of Occupational Hygiene 46(Suppl 1):132–135. ILSI (International Life Sciences Institute). 2005. Testing of fibrous par- ticles: Short-term assays and strategies. Report of an ILSI Risk Sci- ence Institute Working Group. Inhalation Toxicology 17(10):497– 537. IMA (International Mineralogical Association). 2009. Commission on New Minerals, Nomenclature and Classification. http://www.ima- mineralogy.org (accessed June 22, 2009). Jaurand, M. C. 1996. Use of in vitro genotoxicity and cell transformation assays to evaluate the potential carcinogenicity of fibres. In Mecha- nisms of fibre carcinogenesis, edited by A. B. Kane, P. Boffetta, R. Saracci, and J. D. Wilbourn. IARC 140. Lyon: IARC. Pp. 55–72. Kelse, J. W. 2005. White Paper: Asbestos, health risk and tremolitic talc. Norwalk, CT: RT Vanderbilt Co. Inc. As cited in NIOSH, 2009. Krishnamoorthy, K., and T. Mathew. 2002. Statistical methods for estab- lishing equivalency of a sampling device to the OSHA standard. American Industrial Hygiene Association Journal 63:567–571.

OCR for page 33
72 REVIEW OF THE NIOSH ROADMAP Krishnamoorthy, K., and T. Mathew. 2003. Inferences on the means of lognormal distributions using generalized p-values and generalized confidence intervals. Journal of Statistical Planning and Inference 115:103–121. Krishnamoorthy, K., T. Mathew, and G. Ramachandran. 2006. General- ized p-values and confidence intervals: A novel approach for analyz- ing lognormally distributed exposure data. Journal of Occupational and Environmental Hygiene 3:642–650. Krishnamoorthy, K., A. Mallick, and T. Mathew. 2009. Model based imputation approach for data analysis in the presence of non- detectable values: Normal and related distributions. Annals of Occu- pational Hygiene 59:249–268. Leake, B.E., A. R. Woolley, C. E. S. Arps, W. D. Birch, M. C. Gilbert, J. D. Grice, F. C. Hawthorne, A. Kato, H. J. Kisch, V. G. Krivovi- chev, K. Linthout, J. Laird, J. A. Mandarino, W. V. Maresch, E. H. Nickel, N. M. S. Rock, J. C. Schumacher, D. C. Smith, N. C. N. Ste- phenson, L. Ungaretti, E. J. W. Whittaker, and G. Youshi. 1997. Nomenclature of amphiboles: Report of the subcommittee on amphi- boles of the International Mineralogical Association, Commission on New Minerals and Mineral Names. American Mineralogist 82:1019– 1037. Leake, B. E., A. R. Woolley, W. D. Birch, E. A. J. Burke, G. Ferraris, J. D. Grice, F. C. Hawthorne, H. J. Kisch, V. G. Krivovichev, J. C. Schumacher, N. C. N. Stephenson, and E. J. W. Whittaker. 2004. Nomenclature of amphiboles: Additions and revisions to the Interna- tional Mineralogical Association’s amphibole nomenclature. Ameri- can Mineralogist 89:883–887. Lippmann, M. 1988. Asbestos exposure indices. Environmental Research 46:86–106. Lowers, H., and G. Meeker. 2002. Tabulation of asbestos-related terminology. U.S. Geological Survey Open-File Report 02-0458. http://pubs.usgs.gov/of/2002/ofr-02-458 (accessed October 5, 2009). Luce, D., I. Bugel, P. Goldberg, M. Goldberg, C. Salomon, M. A. Billon- Galland, J. Nicolau, P. Quénel, J. Fevotte, P. Brochard. 2000. Environmental exposure to tremolite and respiratory cancer in New Caledonia: A case-control study. American Journal of Epidemiology 151(3): 259–265. Luce, D., M. A. Billon-Galland, I. Bugel, P. Goldberg, C. Salomon, J. Févotte, and M. Goldberg. 2004. Assessment of environmental and

OCR for page 33
73 MAJOR SCIENTIFIC ISSUES domestic exposure to tremolite in New Caledonia. Archives of Envi- ronmental Health 59(2):91–100. Mauderly, J. L. 1997. Relevance of particle-induced rat lung tumors for assessing lung carcinogenic hazard and human lung cancer risk. En- vironmental Health Perspectives 105(Suppl 5):1337–1346. Maxim, L. D., J. G. Hadley, R. M. Potter, and R. Niebo. 2006. The role of fiber durability/biopersistence of silica-based synthetic vitreous fibers and their influence on toxicology. Regulatory Toxicology and Pharmacology 46:42–62. McDonald, J. C., G. W. Gibbs, F. D. K. Liddel, and A. D. McDonald. 1978. Mortality after long exposure to cummingtonite-grunerite. American Review of Respiratory Disease 118:271–277. MDH (Minnesota Department of Health). 2007. Mesothelioma in north- eastern Minnesota and two occupational cohorts: 2007 update. St. Paul, MN: Minnesota Department of Health. http://www. health.state.mn.us/divs/hpcd/cdee/mcss/documents/nemeso1207.p df (accessed June 30, 2008). Menvielle, G., D. Luce, J. Févotte, I. Bugel, C. Salomon, P. Goldberg, M. A. Billon-Galland, M. Goldberg. 2003. Occupational exposures and lung cancer in New Caledonia. Occupational and Environmental Medicine 60(8):584–589. Mikalsen, S. O., E. Rivedal, and T. Sanner. 1988. Morphological trans- formation of Syrian hamster embryo cells induced by mineral fibres and the alleged enhancement of benzo[a]pyrene. Carcinogenesis 9(6):891–899. Neuendorf, K. K. E., J. P. Mehl, Jr., and J. A. Jackson, eds. 2005. Glos- sary of geology, 5th edition. Alexandria, VA: American Geological Institute. Nickel, E. H., and J. D. Grice. 1998. The IMA Commission on New Minerals and Mineral Names: Procedures and guidelines on mineral nomenclature, 1998. Canadian Mineralogist 36:1–16. Nikula, K. J., M. B. Snipes, E. B. Barr, W. C. Griffith, R. F. Henderson, and J. L. Mauderly. 1995. Comparative pulmonary toxicities and carcinogenicities of chronically inhaled diesel exhaust and carbon black in F344 rats. Fundamental and Applied Toxicology 25:80–94. NIOSH (National Institute for Occupational Safety and Health). 1980. Occupational exposure to talc containing asbestos. Cincinatti: NIOSH. DHEW (NIOSH) Publication No. 80-115. http://www.cdc. gov/niosh/review/public/099/pdfs/TalcContainingAsbestosTR.pdf (accessed September 16, 2009).

OCR for page 33
74 REVIEW OF THE NIOSH ROADMAP NIOSH. 2009. Revised draft. NIOSH current intelligence bulletin. Asbes- tos fibers and other elongated mineral particles: State of the science and roadmap for research. January 2009. Department of Health and Human Services, Centers for Disease Control and Prevention, National Institute for Occupational Safety and Health. http:// www.cdc.gov/niosh/docket/pdfs/NIOSH-099b/099B-040109Asbestos NAReviewDoc.pdf (accessed September 18, 2009). NRC (National Research Council). 2007. Toxicity testing in the twenty- first century: A vision and a strategy. Washington, DC: The National Academies Press. Oberdörster G. 1995. Lung particle overload: Implications for occupa- tional exposures to particles. Regulatory Toxicology and Pharmacol- ogy 21(1):123–135. Park, S.H., and A. E. Aust. 1998. Participation of iron and nitric oxide in the mutagenicity of asbestos in hgprt-, gpt+ Chinese hamster V79 cells. Cancer Research 58:1144–1148. Piao, C. Q., Y. L. Zhao, and T. K. Hei. 2001. Analysis of p16 and p21(Cip1) expression in tumorigenic human bronchial epithelial cells induced by asbestos. Oncogene 20(50):7301–7306. Sakellariou, K., V. Malamou-Mitsi, A. Haritou, C. Koumpaniou, C. Stachouli, I. D. Dimoliatis, S. H. Constantopoulos. 1996. Malignant pleural mesothelioma from nonoccupational asbestos ex- posure in Metsovo (north-west Greece): Slow end of an epidemic? European Respiratory Journal 9(6):1206–1210. Schins, R., and T. K. Hei. 2006. Genotoxic effects of particles. In Parti- cle toxicology, edited by K. Donaldson and P. Borm. London: CRC Press. Pp. 287–300. Sebastian, K., J. Fellman, R. Potter, et al. 2002. EURIMA test guideline: In-vitro acellular dissolution of manmade vitreous silicate fibres. Technical report. Glastechnische Berichte—Glass Science and Tech- nology 75(5):263–270. Senyiğit, A., C. Babayiğit, M. Gökirmak, F. Topçu, E. Asan, M. Coşkunsel, R. Işik, and M. Ertem. 2000. Incidence of malignant pleural meso- thelioma due to environmental asbestos fiber exposure in the south- east of Turkey. Respiration 67(6):610–614. Shukla, A., M. B. MacPherson, J. Hillegass, M. E. Ramos-Ning, V. Alexeeva, P. M. Vacek, J. P. Bond, H. I. Pass, C. Steele, and B. T. Mossman. 2009. Alterations in gene expression in human mesothe- lial cells correlated with mineral pathogenicity. American Journal of Respiratory Cell Molecular Biology 41:114–123.

OCR for page 33
75 MAJOR SCIENTIFIC ISSUES Steenland, K., and D. Brown. 1995. Mortality study of gold miners ex- posed to silica and nonasbestiform amphibole minerals: An update with 14 more years of followup. American Journal of Industrial Medicine 27:217–229. Sullivan, P. 2007. Vermiculite, respiratory disease and asbestos exposure in Libby, Montana: Update of a cohort mortality study. Environ- mental Health Perspectives 115:579–585. U.S. Court of Appeals Ninth Circuit. 2007. U.S. v. W. R. Grace. http://www.ca9.uscourts.gov/datastore/opinions/2007/09/20/0630472.pdf (accessed July 9, 2009). Vianna, N. J., J. Maslowsky, S. Robert, G. Spellman, and B. Patton. 1981. Malignant mesothelioma: Epidemiologic patterns in New York State. New York State Journal of Medicine 81:735–738. Wagner, J. C., G. Berry, V. Timbrell. 1973. Mesothelioma in rats after inoculation with asbestos and other materials. British Journal of Cancer 28(2):173–185. Wagner, J. C., G. Berry, J. W. Skidmore, V. Timbrell. 1974. The effects of the inhalation of asbestos in rats. British Journal of Cancer 29(3):252–269. Wagner, J. C., G. B. Berry, R. J. Hill, D. E. Munday, et al. 1982. Animal experiments with MMM(V)F — Effects of inhalation and intrapleu- ral inoculation in rats. In: Biological effects on man-made mineral fi- bers. Vol. 2. WHO/IARC Conference, Copenhagen, April 20–22, 1982. Pp. 209–233. Wang, Y., S. P. Faux, G. Hallden, D. H. Kirn, C. E. Houghton, N. R. Lemoine, and G. Patrick. 2004. Interleukin-1 beta and tumor necrosis factor alpha promotes the transformation of human immortalized mesothelial cells by erionite. International Journal of Oncology 25:173–178. Xu, A., S. Huang, Y. Lien, D. Yu, and T. K. Hei. 2007. Genotoxic mechanisms of asbestos fibers: Role of extranuclear targets. Chemi- cal Research in Toxicology 20:724–733. Zhao, Y. L., C. Q. Piao, L. J. Wu, M. Suzuki, and T. K Hei. 2000. Dif- ferentially expressed genes in asbestos-induced tumorigenic human bronchial epithelial cells: Implications for mechanism. Carcino- genesis 21:2005–2010. Zoitos, B. K., A. de Meringo, E. Rouyer, S. Thélohan, J. Bauer, B. Law, P. M. Boymel, R. Olson, V. R. Christensen, M. Guldberg, A. R. Koenig, and M. Perander. 1997. In vitro measurement of fiber dis-

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76 REVIEW OF THE NIOSH ROADMAP solution rate relevant to biopersistence at neutral pH: An interlabo- ratory round robin. Inhalation Toxicology 9(6):525–540.