DEPARTMENT OF HEALTH AND HUMAN SERVICES

Centers for Disease Control and Prevention

National Institute for Occupational Safety and Health

CURRENT INTELLIGENCE BULLETIN 62

Asbestos Fibers and Other Elongate 

Mineral Particles: State of the Science

and Roadmap for Research

Revised Edition
Cover Photograph: Transitional particle from upstate New York identified by the 

United States Geological Survey (USGS) as anthophyllite asbestos altering to talc. 

Photograph courtesy of USGS.
CURRENT INTELLIGENCE BULLETIN 62

Asbestos Fibers and Other Elongate 

Mineral Particles: State of the Science 

and Roadmap for Research

DEPARTMENT OF HEALTH AND HUMAN SERVICES

Centers for Disease Control and Prevention

National Institute for Occupational Safety and Health 
ii

This document is in the public domain and may be freely copied or 

reprinted.

Disclaimer 

Mention of any company or product does not constitute endorsement by the National Institute for Occupational Safety and Health (NIOSH). In addition, citations 

to Web sites external to NIOSH do not constitute NIOSH endorsement of the sponsoring organizations or their programs or products. Furthermore, NIOSH is not 

responsible for the content of these Web sites. 

Ordering Information 

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For a monthly update on news at NIOSH, subscribe to NIOSH eNews by visiting 

www.cdc.gov/niosh/eNews. 

DHHS (NIOSH) Publication No. 2011–159

(Revised for clarification; no changes in substance or new science presented)

April 2011

Safer • Healthier • PeopleTM
iii

Foreword

Asbestos has been a highly visible issue in public health for over three decades. 

During the mid- to late-20th century, many advances were made in the scientific 

understanding of worker health effects from exposure to asbestos fibers and other 

elongate mineral particles (EMPs). It is now well documented that asbestos fibers, 

when inhaled, can cause serious diseases in exposed workers. However, many questions and areas of confusion and scientific uncertainty remain. 

The National Institute for Occupational Safety and Health (NIOSH) has determined 

that exposure to asbestos fibers causes cancer and asbestosis in humans on the basis of evidence of respiratory disease observed in workers exposed to asbestos, and 

recommends that exposures be reduced to the lowest feasible concentration. As the 

federal agency responsible for conducting research and making recommendations 

for the prevention of worker injury and illness, NIOSH has undertaken a reappraisal 

of how to ensure optimal protection of workers from exposure to asbestos fibers and 

other EMPs. As a first step in this effort, NIOSH convened an internal work group 

to develop a framework for future scientific research and policy development. The 

NIOSH Mineral Fibers Work Group prepared a first draft of this State of the Science 

and Roadmap for Scientific Research (herein referred to as the Roadmap), summarizing NIOSH’s understanding of occupational exposure and toxicity issues concerning asbestos fibers and other EMPs. 

NIOSH invited comments on the occupational health issues identified and the 

framework for research suggested in the first draft Roadmap. NIOSH sought other views about additional key issues that should be identified, additional research 

that should be conducted, and methods for conducting the research. In particular, 

NIOSH sought input from stakeholders concerning study designs, techniques for 

generating size-selected fibers, analytic approaches, sources of particular types of 

EMPs suitable for experimental studies, and worker populations suitable for epidemiological study. On the basis of comments received during the public and expert 

peer review process, NIOSH revised the Roadmap and invited public review of the 

revised version by stakeholders. After further revision and public comment, a revised draft Roadmap was submitted for review by the National Academies of Science 

in early 2009. Based on the National Academies assessment of the draft Roadmap, 

revisions were made, and NIOSH disseminated a fourth draft version of the document for final public comment in early 2010. After considering these comments, 

NIOSH has developed this final revision of the Roadmap.

The purpose of this Roadmap is to outline a research agenda that will guide the development of specific research programs and projects that will lead to a broader and 
iv

clearer understanding of the important determinants of toxicity for asbestos fibers 

and other EMPs. NIOSH recognizes that results from such research may impact environmental as well as occupational health policies and practices. Many of the issues 

that are important in the workplace are also important to communities and to the 

general population. Therefore, NIOSH envisions that the planning and conduct of 

the research will be a collaborative effort involving active participation of multiple 

federal agencies, including the Agency for Toxic Substances and Disease Registry 

(ATSDR), the Consumer Product Safety Commission (CPSC), the Environmental 

Protection Agency (EPA), the Mine Safety and Health Administration (MSHA), the 

National Institute of Environmental Health Sciences (NIEHS), the National Institute 

of Standards and Technology (NIST), the National Toxicology Program (NTP), the 

Occupational Safety and Health Administration (OSHA), and the United States Geological Survey (USGS), as well as labor, industry, academia, health and safety practitioners, and other interested parties, including international groups. This collaboration will help to focus the scope of the research, to fund and conduct the research, 

and to develop and disseminate informational materials describing research results 

and their implications for establishing new occupational and public health policies. 

This Roadmap also includes a clarified rewording of the NIOSH recommended exposure limit (REL) for airborne asbestos fibers. This clarification is not intended to 

establish a new NIOSH occupational health policy for asbestos, and no regulatory 

response by OSHA or MSHA is requested or expected. 

John Howard, MD

Director, National Institute for

Occupational Safety and Health

Centers for Disease Control and Prevention 
v

Executive Summary 

In the 1970s, NIOSH determined that exposure to asbestos fibers causes cancer and 

asbestosis in humans on the basis of evidence of respiratory disease observed in 

workers exposed to asbestos. Consequently, it made recommendations to the federal enforcement agencies on how to reduce workplace exposures. The enforcement 

agencies developed occupational regulatory definitions and standards for exposure 

to airborne asbestos fibers based on these recommendations. Since the promulgation of these standards, which apply to occupational exposures to the six commercially used asbestos minerals—the serpentine mineral chrysotile, and the amphibole 

minerals cummingtonite-grunerite asbestos (amosite), riebeckite asbestos (crocidolite), actinolite asbestos, anthophyllite asbestos, and tremolite asbestos—the use of 

asbestos in the United States has declined substantially and mining of asbestos in the 

United States ceased in 2002. Nevertheless, many asbestos products remain in use 

and new asbestos-containing products continue to be manufactured in or imported 

into the United States.

As more information became available on the relationship between the dimensions 

of asbestos fibers and their ability to cause nonmalignant respiratory disease and 

cancer, interest increased in exposure to other “mineral fibers.” The term “mineral 

fiber” has been frequently used by nonmineralogists to encompass thoracic-size 

elongate mineral particles (EMPs) occurring either in an asbestiform habit (e.g., asbestos fibers) or in a nonasbestiform habit (e.g., as needle-like [acicular] or prismatic crystals), as well as EMPs that result from the crushing or fracturing of nonfibrous 

minerals (e.g., cleavage fragments). Asbestos fibers are clearly of substantial health 

concern. Further research is needed to better understand health risks associated 

with exposure to other thoracic-size EMPs, including those with mineralogical 

compositions identical or similar to the asbestos minerals and those that have already been documented to cause asbestos-like disease, as well as the physicochemical characteristics that determine their toxicity. 

Imprecise terminology and mineralogical complexity have affected progress in research. “Asbestos” and “asbestiform” are two commonly used terms that lack mineralogical precision. “Asbestos” is a term used for certain minerals that have crystallized 

in a particular macroscopic habit with certain commercially useful properties. These 

properties are less obvious on microscopic scales, and so a different definition of asbestos may be necessary at the scale of the light microscope or electron microscope, 

involving characteristics such as chemical composition and crystallography. “Asbestiform” is a term applied to minerals with a macroscopic habit similar to that of asbestos. The lack of precision in these terms and the difficulty in translating macroscopic 
vi

properties to microscopically identifiable characteristics contribute to miscommunication and uncertainty in identifying toxicity associated with various forms of minerals. Deposits may have more than one mineral habit and transitional minerals may be 

present, which make it difficult to clearly and simply describe the mineralogy.

In 1990, NIOSH revised its recommendation concerning occupational exposure to 

airborne asbestos fibers. At issue were concerns about potential health risks associated 

with worker exposures to the analogs of the asbestos minerals that occur in a different habit—so-called cleavage fragments—and the inability of the analytical method 

routinely used for characterizing airborne exposures (i.e., phase contrast microscopy 

[PCM]) to differentiate nonasbestiform analogs from asbestos fibers on the basis of 

physical appearance. This problem was further compounded by the lack of more sensitive analytical methods that could distinguish asbestos fibers from other EMPs having 

the same elemental composition. To address these concerns and ensure that workers 

are protected, NIOSH defined “airborne asbestos fibers” to encompass not only fibers 

from the six previously listed asbestos minerals (chrysotile, crocidolite, amosite, anthophyllite asbestos, tremolite asbestos, and actinolite asbestos) but also EMPs from 

their nonasbestiform analogs. NIOSH retained the use of PCM for measuring airborne fiber concentrations and counting those EMPs having: (1) an aspect ratio of 3:1 

or greater and (2) a length greater than 5 μm. NIOSH also retained its recommended 

exposure limit (REL) of 0.1 airborne asbestos fiber per cubic centimeter (f/cm3). 

Since 1990, several persistent concerns have been raised about the revised NIOSH 

recommendation. These concerns include the following:

• NIOSH’s explicit inclusion of EMPs from nonasbestiform amphiboles in its 

1990 revised definition of airborne asbestos fibers is based on inconclusive science and contrasts with the regulatory approach subsequently taken by OSHA 

and by MSHA. 

• The revised definition of airborne asbestos fibers does not explicitly encompass 

EMPs from asbestiform amphiboles that formerly had been mineralogically defined as tremolite (e.g., winchite and richterite) or other asbestiform minerals 

that are known to be (e.g., erionite and fluoro-edenite) or may be (e.g., some 

forms of talc) associated with health effects similar to those caused by asbestos. 

• The specified dimensional criteria (length and aspect ratio) for EMPs covered 

by the revised definition of airborne asbestos fibers may not be optimal for 

protecting the health of exposed workers because they are not based solely on 

health concerns.

• Other physicochemical parameters, such as durability and surface activity, 

may be important toxicological parameters but are not reflected in the revised 

definition of airborne asbestos fibers.

• NIOSH’s use of the term “airborne asbestos fibers” to describe all airborne 

EMPs covered by the REL differs from the way mineralogists use the term and 

this inconsistency leads to confusion about the toxicity of EMPs. 
vii

NIOSH recognizes that its 1990 description of the particles covered by the REL for 

airborne asbestos fibers has created confusion, causing many to infer that the nonasbestiform minerals included in the NIOSH definition are “asbestos.” Therefore, 

in this Roadmap, NIOSH makes clear that such nonasbestiform minerals are not 

“asbestos” or “asbestos minerals,” and clarifies which particles are included in the 

REL. This clarification also provides a basis for a better understanding of the need 

for the proposed research. Clarification of the REL in this way does not change the 

existing NIOSH occupational health policy for asbestos, and no regulatory response 

by OSHA or MSHA is requested or expected. The REL remains subject to revision 

based on findings of ongoing and future research.

PCM, the primary method specified by NIOSH, OSHA, and MSHA for analysis of 

air samples for asbestos fibers, has several limitations, including limited ability to 

resolve very thin fibers and to differentiate various types of EMPs. Occupational 

exposure limits for asbestos derive from lung cancer risk estimates from exposure of 

workers to airborne asbestos fibers in commercial processes. These risk assessments 

are based on fiber concentrations determined from a combination of PCM-based 

fiber counts on membrane filter samples and fiber counts estimated from impinger 

samples. The standard PCM method counts only fibers longer than 5 μm. Moreover, 

some fibers longer than 5 μm may be too thin to be detected by PCM. Thus, an undetermined number of fibers collected on each sample remain uncounted by PCM. 

More sensitive analytical methods are currently available, but standardization and 

validation of these methods will be required before they can be recommended for 

routine analysis. However, unlike PCM, these methods are substantially more expensive, and field instruments are not available. In addition, any substantive change 

in analytical techniques used to evaluate exposures to asbestos and/or the criteria 

for determining exposure concentrations will necessitate a reassessment of current 

risk estimates, which are based on PCM-derived fiber concentrations.

Epidemiological evidence clearly indicates a causal relationship between exposure 

to fibers from the asbestos minerals and various adverse health outcomes, including 

asbestosis, lung cancer, and mesothelioma. However, NIOSH has viewed as inconclusive the results from epidemiological studies of workers exposed to EMPs from 

the nonasbestiform analogs of the asbestos minerals. Populations of interest for 

possible epidemiological studies include workers at talc mines in upstate New York 

and workers at taconite mines in northeastern Minnesota. Others include populations exposed to other EMPs, such as winchite and richterite fibers (asbestiform 

EMPs identified in vermiculite from a former mine near Libby, Montana), zeolites 

(such as asbestiform erionite), and other minerals (such as fluoro-edenite). Future 

studies should include detailed characterizations of the particles to which workers 

are or have been exposed.

There is considerable potential for experimental animal and in vitro studies to address specific scientific questions relating to the toxicity of EMPs. Short-term in 

vivo animal studies and in vitro studies have been conducted to examine cellular 

and tissue responses to EMPs, identify pathogenic mechanisms involved in those 
viii

responses, and understand morphological and/or physicochemical EMP properties 

controlling those mechanisms. Long-term studies of animals exposed to EMPs have 

been conducted to assess the risk for adverse health outcomes (primarily lung cancer, mesothelioma, and lung fibrosis) associated with various types and dimensions 

of EMPs. Such studies have produced evidence demonstrating the importance of 

dimensional characteristics of mineral particles for determining carcinogenic potential of durable EMPs. Although in vitro studies and animal studies are subject to 

uncertainties with respect to how their findings apply to humans, such studies are 

warranted to systematically assess and better understand the impacts of dimension, 

morphology, chemistry, and biopersistence of EMPs on malignant and nonmalignant respiratory disease outcomes.

To reduce existing scientific uncertainties and to help resolve current policy controversies, a strategic research program is needed that encompasses endeavors in 

toxicology, exposure assessment, epidemiology, mineralogy, and analytical methods. The findings of such research can contribute to the development of new policies 

for exposures to airborne asbestos fibers and other EMPs with recommendations 

for exposure indices that are not only more effective in protecting workers’ health 

but firmly based on quantitative estimates of health risk. To bridge existing scientific uncertainties, this Roadmap proposes that interdisciplinary research address 

the following three strategic goals: (1) develop a broader and clearer understanding of the important determinants of toxicity for EMPs, (2) develop information 

on occupational exposures to various EMPs and health risks associated with such 

exposures, and (3) develop improved sampling and analytical methods for asbestos 

fibers and other EMPs. 

Developing a broader and clearer understanding of the important determinants of 

toxicity for EMPs will involve building on what is known by systematically conducting in vitro studies and in vivo animal studies to ascertain which physical and 

chemical properties of EMPs influence their toxicity and their underlying mechanisms of action in causing disease. The in vitro studies could provide information on 

membranolytic, cytotoxic, and genotoxic activities as well as signaling mechanisms. 

The in vivo animal studies should involve a multispecies testing approach for shortterm assays to develop information for designing chronic inhalation studies and to 

develop information on biomarkers and mechanisms of disease. Chronic animal 

inhalation studies are required to address the impacts of dimension, morphology, 

chemistry, and biopersistence on critical disease endpoints, including cancer and 

nonmalignant respiratory disease. Chronic inhalation studies should be designed 

to provide solid scientific evidence on which to base human risk assessments for 

a variety of EMPs. The results of toxicity studies should be assessed in the context 

of results of epidemiologic studies to provide a basis for understanding the human 

health effects of exposure to EMPs for which epidemiologic studies are not available. 

Developing information and knowledge on occupational exposures to various 

EMPs and potential health outcomes will involve (1) collecting and analyzing available occupational exposure information to ascertain the characteristics and extent 
ix

of exposure to various types of EMPs; (2) collecting and analyzing available information on health outcomes associated with exposures to various types of EMPs; 

(3) conducting epidemiological studies of workers exposed to various types of EMPs 

to better define the association between exposure and health effects; and (4) developing and validating methods for screening, diagnosis, and secondary prevention 

for diseases caused by exposure to asbestos fibers and other EMPs. 

Developing improved sampling and analytical methods for EMPs will involve (1) reducing interoperator and interlaboratory variability of currently used analytical 

methods; (2) developing a practical analytical method that will permit the counting, 

sizing, and identification of EMPs; (3) developing a practical analytical method that 

can assess the potential durability of EMPs as one determinant of biopersistence 

in the lung; and (4) developing and validating size-selective sampling methods for 

collecting and quantifying airborne thoracic-size asbestos fibers and other EMPs.

A primary anticipated outcome of the research that is broadly outlined in this Roadmap will be the identification of the physicochemical parameters such as chemical 

composition, dimensional attributes (e.g., ranges of length, width, and aspect ratio), 

and durability as predictors of biopersistence, as well as particle surface characteristics or activities (e.g., generation reactive oxygen species [ROS]) as determinants 

of toxicity of asbestos fibers and other EMPs. The results of the research will also 

help define the sampling and analytical methods that closely measure the important 

toxic characteristics and need to be developed. These results can then inform development of appropriate recommendations for worker protection.

Another outcome of the research that is broadly outlined in this Roadmap might be the 

development of criteria that could be used to predict, on the basis of results of in vitro

testing and/or short-term in vivo testing, the potential risk associated with exposure 

to any particular type of EMP. This could reduce the need for comprehensive toxicity 

testing with long-term in vivo animal studies and/or epidemiological evaluation of each 

type of EMP. Ultimately, the results from such studies could be used to fill in knowledge 

gaps beyond EMPs to encompass predictions of relative toxicities and adverse health 

outcomes associated with exposure to other elongate particles (EPs), including inorganic and organic manufactured particles. A coherent risk management approach that 

fully incorporates an understanding of the toxicity of particles could then be developed 

to minimize the potential for disease in exposed individuals and populations. 

This Roadmap is intended to outline the scientific and technical research issues that 

need to be addressed to ensure that workers are optimally protected from health 

risks posed by exposures to asbestos fibers and other EMPs. Achievement of the 

research goals framed in this Roadmap will require a significant investment of time, 

scientific talent, and resources by NIOSH and others. This investment, however, can 

result in a sound scientific basis for better occupational health protection policies 

for asbestos fibers and other EMPs.

xi

Contents

Foreword. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . iii

Executive Summary. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . v

List of Figures. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . xiv

List of Tables. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . xiv

Abbreviations . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . xv

Acknowledgments. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . xvii

1 Introduction. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 1

2 Overview of Current Issues. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 5

2.1 Background. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 5

2.2 Minerals and Mineral Morphology. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 6

2.3 Terminology. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 7

2.3.1 Mineralogical Definitions. . . . . . . . . . . . . . . . . . . . . . . . . . . . . 8

2.3.2 Other Terms and Definitions. . . . . . . . . . . . . . . . . . . . . . . . . . . 9

2.4 Trends in Asbestos Use, Occupational Exposures, and Disease. . . . . . . 9

2.4.1 Trends in Asbestos Use. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 9

2.4.2 Trends in Occupational Exposure. . . . . . . . . . . . . . . . . . . . . . . 10

2.4.3 Trends in Asbestos-related Disease. . . . . . . . . . . . . . . . . . . . . . 12

2.5 Workers’ Home Contamination. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 14

2.6 Clinical Issues. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 15

2.7 The NIOSH Recommendation for Occupational Exposure 

to Asbestos. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 17

2.7.1 The NIOSH REL as Revised in 1990. . . . . . . . . . . . . . . . . . . . . 18

2.7.2 Clarification of the Current NIOSH REL. . . . . . . . . . . . . . . . . 33

2.8 EMPs Other than Cleavage Fragments. . . . . . . . . . . . . . . . . . . . . . . . . . . . 34

2.8.1 Chrysotile. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 34

2.8.2 Asbestiform Amphibole Minerals. . . . . . . . . . . . . . . . . . . . . . . 36

2.8.3 Other Minerals of Potential Concern. . . . . . . . . . . . . . . . . . . . 38

 2.9 Determinants of Particle Toxicity and Health Effects. . . . . . . . . . . . . . . . 39

2.9.1 Deposition. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 39

2.9.2 Clearance and Retention. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 40
xii

2.9.3 Biopersistence and other Potentially Important

Particle Characteristics. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 42

2.9.4 Animal and In Vitro Toxicity Studies. . . . . . . . . . . . . . . . . . . . 46

2.9.5 Thresholds. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 58

2.10 Analytical Methods. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 60

2.10.1 NIOSH Sampling and Analytical Methods for

Standardized Industrial Hygiene Surveys. . . . . . . . . . . . . . . . . 62

2.10.2 Analytical Methods for Research. . . . . . . . . . . . . . . . . . . . . . . 63

2.10.3 Differential Counting and Other Proposed Analytical 

 Approaches for Differentiating EMPs. . . . . . . . . . . . . . . . . . 65

2.11 Summary of Key Issues. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 66

3 Framework for Research. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 69

3.1 Strategic Research Goals and Objectives. . . . . . . . . . . . . . . . . . . . . . . . . . . 70

3.2 An Approach to Conducting Interdisciplinary Research. . . . . . . . . . . . . . . 70

3.3 National Reference Repository of Minerals and 

Information System. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 70

3.4 Develop a Broader Understanding of the Important Determinants 

of Toxicity for Asbestos Fibers and Other EMPs. . . . . . . . . . . . . . . . . . . . 71

3.4.1 Conduct In Vitro Studies to Ascertain the Physical and 

Chemical Properties that Influence the Toxicity of 

Asbestos Fibers and Other EMPs. . . . . . . . . . . . . . . . . . . . . . . 76

3.4.2 Conduct Animal Studies to Ascertain the Physical and 

Chemical Properties that Influence the Toxicity of 

Asbestos Fibers and Other EMPs. . . . . . . . . . . . . . . . . . . . . . . 78

3.4.3 Evaluate Toxicological Mechanisms to Develop 

Early Biomarkers of Human Health Effects. . . . . . . . . . . . . . . 81

3.5 Develop Information and Knowledge on Occupational Exposures to 

Asbestos Fibers and Other EMPs and Related Health Outcomes . . . . . 81

3.5.1 Assess Available Information on Occupational Exposures 

to Asbestos Fibers and Other EMPs . . . . . . . . . . . . . . . . . . . . 82

3.5.2 Collect and Analyze Available Information on Health 

Outcomes Associated with Exposures to Asbestos Fibers 

and Other EMPs. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 83

3.5.3 Conduct Selective Epidemiological Studies of Workers 

Exposed to Asbestos Fibers and Other EMPs. . . . . . . . . . . . . 84

3.5.4 Improve Clinical Tools and Practices for Screening, 

Diagnosis, Treatment, and Secondary Prevention of 

Diseases Caused by Asbestos Fibers and Other EMPs. . . . . . 87
xiii

3.6 Develop Improved Sampling and Analytical Methods for 

Asbestos Fibers and Other EMPs. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 88

3.6.1 Reduce Inter-operator and Inter-laboratory Variability of 

the Current Analytical Methods Used for Asbestos Fibers. . 90

3.6.2 Develop Analytical Methods with Improved Sensitivity to 

Visualize Thinner EMPs to Ensure a More Complete 

Evaluation of Airborne Exposures. . . . . . . . . . . . . . . . . . . . . . 91

3.6.3 Develop a Practical Analytical Method for Air Samples 

to Differentiate Asbestiform Fibers from the Asbestos

Minerals and EMPs from Their Nonasbestiform Analogs. . 92

3.6.4 Develop Analytical Methods to Assess Durability 

of EMPs. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 93

3.6.5 Develop and Validate Size-selective Sampling Methods 

for EMPs. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 93

3.7 From Research to Improved Public Health Policies for 

Asbestos Fibers and Other EMPs . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 94

4 The Path Forward. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 99

4.1 Organization of the Research Program. . . . . . . . . . . . . . . . . . . . . . . . . . . . 99

4.2 Research Priorities. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 100

4.3 Outcomes. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 101

5 References. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 103

6 Glossary. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 131

6.1 NIOSH Definition of Potential Occupational Carcinogen. . . . . . . . . . . . 131

6.2 Definitions of New Terms Used in this Roadmap. . . . . . . . . . . . . . . . . . . 131

6.3 Definitions of Inhalational Terms. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 131

6.4 Definitions of General Mineralogical Terms and Specific Minerals. . . . 132

6.5 References for Definitions of General Mineralogical Terms,

Specific Mineral and Inhalation Terms. . . . . . . . . . . . . . . . . . . . . . . . . . . . 132
xiv

List of Figures

Figure 1. U.S. asbestos production and imports, 1991–2007

Figure 2. Asbestos: Annual geometric mean exposure concentrations by major 

industry division, MSHA and OSHA samples, 1979–2003

Figure 3. Number of asbestosis deaths, U.S. residents aged ≥ 15 years, 1968–2004

Figure 4. Number of deaths due to malignant mesothelioma, U.S. residents aged 

≥ 15 years, 1999–2005

List of Tables

Table 1. Definitions of general mineralogical terms.

Table 2. Definitions of specific minerals.
xv

Abbreviations 

8-OHdG 8-hydroxydeoxyguanosine 

AED aerodynamic equivalent diameter 

AIHA American Industrial Hygiene Association

AP-1 activator protein-1

ASTM ASTM International [previously American Society for Testing 

 and Materials]

ATSDR Agency for Toxic Substances Disease Registry

BAL bronchoalveolar lavage

BrdU bromodeoxyuridine

CI confidence interval

COX-2 cyclooxygenase-2 

CPSC Consumer Product Safety Commission

DM dark-medium microscopy

DNA deoxyribonucleic acid

DPPC dipalmitoyl phosphatidylcholine

ED electron diffraction

EDS energy dispersive X-ray spectroscopy

EGFR epidermal growth factor receptor

EM electron microscopy

EMP elongate mineral particle

EP elongate particle

EPA U.S. Environmental Protection Agency

ERK extracellular signal-regulated kinase

ESR electron spin resonance

f/cm3 fibers per cubic centimeter

f/mL-yr fibers per milliliter-year

HSL/ULO Health and Safety Laboratory/UL Optics

ICD International Classification of Diseases

IgG immunoglobulin G

IL interleukin

IMA International Mineralogical Association

IMIS Integrated Management Information System

IP intraperitoneal

ISO International Organization for Standardization

L liter

LDH lactate dehydrogenase

LOQ limit of quantification

MDH Minnesota Department of Health

mg/m3-d milligrams per cubic meter-days
xvi

MAPK mitogen-activated protein kinase

MMAD mass median aerodynamic diameter

MMMF man-made mineral fiber

MMVF man-made vitreous fiber

mppcf million particles per cubic foot

MSHA Mine Safety and Health Administration

mRNA messenger ribonucleic acid

NADPH nicotinamide adenine dinucleotide phosphate 

NFκB nuclear factor kappa beta

NIEHS National Institute of Environmental Health Sciences

NMRD nonmalignant respiratory disease

NIOSH National Institute for Occupational Safety and Health

NIST National Institute of Standards and Technology

NORA National Occupational Research Agenda

NORMS National Occupational Respiratory Mortality System

NTP National Toxicology Program

OSHA Occupational Safety and Health Administration

PCMe phase contrast microscopy equivalent

PCM phase contrast microscopy

PEL permissible exposure limit

RCF refractory ceramic fiber

REL recommended exposure limit

ROS reactive oxygen species

RTV RT Vanderbilt Company, Inc.

SAED selected area X-ray diffraction 

SEM scanning electron microscopy

SMR standardized mortality ratio

SO superoxide anion

SOD superoxide dismutase

SV40 simian virus 40

SVF synthetic vitreous fiber

SWCNT single-walled carbon nanotubes

TEM transmission electron microscopy

TF tissue factor

TGF transforming growth factor

TNF-α tumor necrosis factor-alpha

TWA time-weighted average

USGS United States Geological Survey

WHO World Health Organization

XPS X-ray photoelectron spectroscopy 
xvii

Acknowledgments 

This document was prepared under the aegis of the NIOSH Mineral Fibers Work 

Group by members of the NIOSH staff. Many internal NIOSH reviewers not listed 

also provided critical feedback important to the preparation of this Roadmap. 

The NIOSH Mineral Fibers Work Group acknowledges the contributions of Jimmy 

Stephens, PhD, former NIOSH Associate Director for Science, who initiated work 

on this document and articulated many of its most critical issues in an early draft.

The NIOSH Mineral Fibers Work Group also acknowledges the contributions of 

Gregory Meeker, USGS, who participated in discussions of the pertinent mineralogy and mineralogical nomenclature.

NIOSH Mineral Fibers Work Group

Paul Baron, PhD

John Breslin, PhD 

Robert Castellan, MD, MPH

Vincent Castranova, PhD 

Joseph Fernback, BS 

Frank Hearl, SMChE

Martin Harper, PhD

Jeffrey Kohler, PhD

Paul Middendorf, PhD, Chair

Teresa Schnorr, PhD

Paul Schulte, PhD

Patricia Sullivan, ScD

David Weissman, MD

Ralph Zumwalde, MS

Major Contributors

Paul Middendorf, PhD

Ralph Zumwalde, MS 

Robert Castellan, MD, MPH

Martin Harper, PhD

William Wallace, PhD

Leslie Stayner, PhD

Vincent Castranova, PhD

Frank Hearl, SMChE

Patricia Sullivan, ScD

Peer Reviewers

NIOSH greatly appreciates the time and efforts of expert peer reviewers who provided comments and suggestions on the initial publicly disseminated draft of the 

Roadmap (February 7, 2007 version).

William Eschenbacher, MD

Group Health Associates 

Morton Lippmann, PhD

New York University

David Michaels, PhD, MPH

George Washington University

Franklin Mirer, PhD

Hunter College
xviii

Brooke Mossman, PhD

University of Vermont

L. Christine Oliver, MD, MPH

Harvard School of Medicine 

William N. Rom, MD, MPH

New York University

Brad Van Gosen, MS

U.S. Geological Survey

Ann Wylie, PhD

University of Maryland

Institutes of Medicine and National Research Council of 

the National Academy of Sciences

NIOSH appreciates the time and efforts of the National Academy of Sciences (NAS) 

committee members, consultant, and study staff who contributed to the development 

of the NAS report A Review of the NIOSH Roadmap for Research on Asbestos Fibers 

and Other Elongate Mineral Particles on the January 2009 version of the draft Roadmap. The individuals contributing to the report are identified in the NAS document.

Document History

Throughout its development, this Roadmap has undergone substantial public comment and scientific peer review with subsequent revision. All external input has 

been considered and addressed, as appropriate, to ultimately produce this final version of the Roadmap. A listing of the various draft versions disseminated for public 

comment and/or scientific peer review is presented here.

February 2007—Draft entitled Asbestos and Other Mineral Fibers: A Roadmap for 

Scientific Research was disseminated for public comment and scientific peer review.

June 2008—Draft entitled Revised Draft NIOSH Current Intelligence Bulletin—

Asbestos Fibers and Other Elongate Mineral Particles: State of the Science and Roadmap for Research was disseminated for public comment.

January 2009—Draft entitled Revised Draft NIOSH Current Intelligence Bulletin—

Asbestos Fibers and Other Elongated Mineral Particles: State of the Science and Roadmap for Research was submitted to the Institute of Medicine and the National Research Council of the National Academies of Science for scientific review.

January 2010—Draft entitled Draft NIOSH Current Intelligence Bulletin—Asbestos 

Fibers and Other Elongate Mineral Particles: State of the Science and Roadmap for 

Research—Version 4 was disseminated for public comment.

March 2011—Final Version of NIOSH Current Intelligence Bulletin—Asbestos Fibers 

and Other Elongate Mineral Particles: State of the Science and Roadmap for Research

was published.
1

1 Introduction

Many workers are exposed to a broad spectrum of inhalable particles in their places 

of work. These particles vary in origin, size, 

shape, chemistry, and surface properties. Considerable research over many years has been 

undertaken to understand the potential health 

effects of these particles and the particle characteristics that are most important in conferring their toxicity. Elongate particles* (EPs) 

have been the subject of much research, and 

the major focus of research on EPs has related 

to asbestos fibers, a group of elongate mineral particles (EMPs) that have long been known 

to cause serious disease when inhaled. Because 

of the demonstrated health effects of asbestos, 

research attention has also been extended not 

only to other EMPs, but also to synthetic vitreous fibers which have dimensions similar to asbestos fibers and, more recently, to engineered 

carbon nanotubes and carbon nanofibers. Although nonmineral EPs are of interest, they are 

not the subject of this Roadmap, which focuses on EMPs. 

Occupational health policies and associated federal regulations controlling occupational exposure to airborne asbestos fibers have 

*

A glossary of technical terms is provided in Section 6. It includes definitions of terms from several standard sources 

in Tables 1 and 2. In general, where a term is used in this 

Roadmap the definitions in Tables 1 and 2 under the column “NIOSH 1990” are intended unless otherwise specified. Readers should be aware that, in reviewing publications cited in this Roadmap, it was not always possible 

to know the meaning of technical terms as used by the 

authors of those publications. Thus, some imprecision of 

terminology carries over into the literature review contained in this Roadmap.

been in existence for decades. Current regulations have been based on studies of the health 

effects of exposures encountered in the commercial exploitation and use of asbestos fibers. 

Nevertheless, important uncertainties remain 

to be resolved to fully inform possible revision 

of existing federal policies and/or development 

of new federal policies to protect workers from 

health effects caused by occupational exposure 

to airborne asbestos fibers. 

Health effects caused by other exposures to 

EMPs have not been studied as thoroughly as 

health effects caused by exposures in the commercial exploitation and use of asbestos fibers. 

Miners and others exposed to asbestiform amphibole fibers associated with vermiculite from 

a mine near Libby, Montana, may not have 

been exposed to commercial asbestos fibers, 

but the adverse health outcomes they have experienced as a result of their exposure have indicated that those EMPs are similarly toxic. 

Other hardrock miner populations face uncertain but potential risk associated with exposures to EMPs that could be generated during mining and processing of nonasbestiform 

amphiboles. Studies of human populations exposed to airborne fibers of erionite, a fibrous 

mineral that is neither asbestos nor amphibole, 

have documented high rates of malignant mesothelioma (a cancer most commonly associated with exposure to asbestos fibers). Further research is warranted to understand how 

properties of EMPs determine toxicity so that 

the nature and magnitude of any potential toxicity associated with an EMP to which workers are exposed can be readily predicted and 
2 NIOSH CIB 62 • Asbestos

controlled, even when exhaustive long-term 

studies of that particular EMP have not been 

carried out.

This Roadmap has been prepared and is being disseminated with the intent of motivating 

eventual development and implementation of 

a coordinated, interdisciplinary research program that can effectively address key remaining 

issues relating to health hazards associated with 

exposure to asbestos fibers and other EMPs. 

Section 2, Overview of Current Issues, provides 

an overview of available scientific information 

and identifies important issues that need to be 

resolved before recommendations for occupational exposure to airborne asbestos fibers and 

related EMPs can be improved and before recommendations for occupational exposure to 

other EMPs can be developed. The nature of occupational exposures to asbestos has changed 

over the last several decades. Once dominated 

by chronic exposures in asbestos textile mills, 

friction product manufacturing, cement pipe 

fabrication, and insulation manufacture and 

installation, occupational exposures to asbestos 

in the United States now primarily occur during maintenance activities or remediation of 

buildings containing asbestos. OSHA has estimated that 1.3 million workers in general industry continue to be exposed to asbestos. In 

2002 NIOSH estimated that about 44,000 mine 

workers might be exposed to asbestos fibers or 

amphibole cleavage fragments during the mining of some mineral commodities. These current occupational exposure scenarios frequently involve short-term, intermittent exposures, 

and proportionately fewer long fibers than 

workers were exposed to in the past. The generally lower current exposures and predominance of short fibers give added significance to 

the question of whether or not there are thresholds for EMP exposure level and EMP length 

below which workers would incur no demonstrable risk of material health impairment. The 

large number of potentially exposed workers 

and these changed exposure scenarios also give 

rise to the need to better understand whether 

appropriate protection is provided by the current occupational exposure recommendations 

and regulations. In addition, limited information is currently available on exposures to, and 

health effects of, other EMPs. 

Section 3, Framework for Research, provides a 

general framework for research needed to address the key issues. NIOSH envisions that this 

general framework will serve as a basis for a 

future interdisciplinary research program carried out by a variety of organizations to (1) elucidate exposures to EMPs, (2) identify any adverse health effects caused by these exposures, 

and (3) determine the influence of size, shape, 

and other physical and chemical characteristics of EMPs on human health. Findings from 

this research would provide a basis for determining which EMPs should be included in 

recommendations to protect workers from 

hazardous occupational exposures along with 

appropriate exposure limits. A fully informed 

strategy for prioritizing research on EMPs will 

be based on a systematic collection and evaluation of available information on occupational 

exposures to EMPs. 

Section 4, The Path Forward, broadly outlines a 

proposed structure for development and oversight of a comprehensive, interdisciplinary research program. Key to this approach will be 

(1) the active involvement of stakeholders representing parties with differing views, (2) expert study groups specifying and guiding various components of the research program, and 

(3) a multidisciplinary group providing careful ongoing review and oversight to ensure relevance, coordination, and impact of the overall 
NIOSH CIB 62 • Asbestos 3

research program. NIOSH does not intend this 

(or any other) section of this Roadmap to be 

prescriptive, so detailed research aims, specific 

research priorities, and funding considerations 

have intentionally not been specified. Rather, it 

is expected that these more detailed aspects of 

the program will be most effectively developed 

with collaborative input from scientists, policy 

experts, and managers from various agencies, 

as well as from other interested stakeholders. 

NIOSH CIB 62 • Asbestos 5

2 Overview of Current Issues

2.1 Background

Prior to the 1970s, concern about the health effects of occupational exposure to airborne fibers was focused on six commercially exploited minerals termed “asbestos:” the serpentine 

mineral chrysotile and the amphibole minerals 

cummingtonite-grunerite asbestos (amosite), 

riebeckite asbestos (crocidolite), actinolite asbestos, anthophyllite asbestos, and tremolite asbestos. The realization that dimensional characteristics of asbestos fibers were important 

physical parameters in the initiation of respiratory disease led to studies of other elongate 

mineral particles (EMPs) of similar dimensions 

[Stanton et al. 1981].

To date, occupational health interest in EMPs 

other than asbestos fibers has been focused primarily on fibrous minerals exploited commercially (e.g., wollastonite, sepiolite, and attapulgite) 

and mineral commodities that contain (e.g., 

Libby vermiculite) or may contain (e.g., upstate 

New York talc) asbestiform minerals. Exposure 

to airborne thoracic-size EMPs generated from 

the crushing and fracturing of nonasbestiform 

amphibole minerals has also garnered substantial interest. The asbestos minerals, as well 

as other types of fibrous minerals, are typically associated with other minerals in geologic 

formations at various locations in the United 

States [Van Gosen 2007]. The biological significance of occupational exposure to airborne 

particles remains unknown for some of these 

minerals and can be difficult to ascertain, given 

the mixed and sporadic nature of exposure in 

many work environments and the general lack 

of well-characterized exposure information.

The complex and evolving terminology used to 

name and describe the various minerals from 

which airborne EMPs are generated has led to 

much confusion and uncertainty in scientific and lay discourse related to asbestos fibers 

and other EMPs. To help reduce such confusion and uncertainty about the content of this 

Roadmap, several new terms are used in this 

Roadmap and defined in the Glossary (Section 6). The Glossary also lists definitions from 

a variety of sources for many other mineralogical and other scientific terms used in this 

Roadmap. Definitions from these sources often vary, and many demonstrate a lack of standardization and sometimes rigor that should 

be addressed by the scientific community.

To address current controversies and uncertainties concerning exposure assessment and 

health effects relating to asbestos fibers and 

other EMPs, strategic research endeavors are 

needed in toxicology, exposure assessment, epidemiology, mineralogy, and analytical methods. The results of such research might inform 

new risk assessments and the potential development of new policies for asbestos fibers and 

other EMPs, with recommendations for exposure limits that are firmly based on wellestablished risk estimates and that effectively 

protect workers’ health. To support the development of these policies, efforts are needed to 

establish a common set of mineral terms that 

unambiguously describe EMPs and are relevant for toxicological assessments. What follows in the remainder of Section 2 is an overview of (1)  definitions and terms relevant to 

asbestos fibers and other EMPs; (2) trends in 
6 NIOSH CIB 62 • Asbestos

production and use of asbestos; (3)  occupational exposures to asbestos and asbestos-related diseases; (4) sampling and analytical issues; 

and (5) physicochemical properties associated 

with EMP toxicity.

2.2 Minerals and Mineral 

Morphology

Minerals are naturally occurring inorganic 

compounds with a specific crystalline structure and elemental composition. Asbestos is a 

term applied to several silicate minerals from 

the serpentine and amphibole groups that occur in a particular type of fibrous habit and 

have properties that have made them commercially valuable. The fibers of all varieties of asbestos are long, thin, and usually flexible when 

separated. One variety of asbestos, chrysotile, 

is a mineral in the serpentine group of sheet 

silicates. Five varieties of asbestos are minerals in the amphibole group of double-chain 

silicates—riebeckite asbestos (crocidolite), 

cummingtonite-grunerite asbestos (amosite), 

anthophyllite asbestos, tremolite asbestos, and 

actinolite asbestos [Virta 2002].

Although a large amount of health information has been generated on workers occupationally exposed to asbestos, limited mineral characterization information and the use of 

nonmineralogical names for asbestos have resulted in uncertainty and confusion about the 

specific nature of exposures described in many 

published studies. Trade names for mined asbestos minerals predated the development of 

rigorous scientific nomenclature. For example, amosite is the trade name for asbestiform 

cummingtonite-grunerite and crocidolite is 

the trade name for asbestiform riebeckite. A 

changing mineralogical nomenclature for amphiboles has also contributed to uncertainty in 

the specific identification of minerals reported 

in the literature. Over the past 50 years, several 

systems for naming amphibole minerals have 

been used. The current mineralogical nomenclature was unified by the International Mineralogical Association (IMA) under a single system in 1978 [Leake 1978] and later modified in 

1997 [Leake et al. 1997]. For some amphibole 

minerals, the name assigned under the 1997 

IMA system is different than the name used 

prior to 1978, but the mineral names specified 

in regulations have not been updated to correlate with the new IMA system names.

Adding to the complexity of the nomenclature, serpentine and amphibole minerals typically develop through the alteration of other 

minerals. Consequently, they may exist as partially altered minerals having variations in elemental compositions. For example, the microscopic analysis of an elongate amphibole 

particle using energy dispersive X-ray spectroscopy (EDS) can reveal variations in elemental composition along the particle’s length, 

making it difficult to identify the particle as a 

single specific amphibole mineral. In addition, 

a mineral may occur in different growth forms, 

or “habits,” so different particles may have different morphologies. However, because they 

share the same range of elemental composition 

and chemical structure and belong to the same 

crystal system, they are the same mineral. Different habits are not recognized as having different mineral names.

Mineral habit results from the environmental 

conditions present during a mineral’s formation. 

The mineralogical terms applied to habits are 

generally descriptive (e.g., fibrous, asbestiform, 

massive, prismatic, acicular, asbestiform, tabular, and platy). Both asbestiform (a specific fibrous type) and nonasbestiform versions 

(i.e., analogs) of the same mineral can occur in 
NIOSH CIB 62 • Asbestos 7

juxtaposition or matrixed together, so that both 

analogs of the same mineral can occur within a 

narrow geological formation.

The habits of amphibole minerals vary, from 

prismatic crystals of hornblende through prismatic or acicular crystals of riebeckite, actinolite, 

tremolite, and others, to asbestiform habits of 

grunerite (amosite), anthophyllite, tremoliteactinolite, and riebeckite (crocidolite). The prismatic and acicular crystal habits occur more 

commonly, and asbestiform habit is relatively rare. Some of the amphiboles, such as 

hornblendes, are not known to occur in an 

asbestiform habit. The asbestiform varieties 

range from finer (flexible) to coarser (more 

brittle) and often are found in a mixture of fine 

and coarse fibrils. In addition, properties vary—

e.g., density of (010) defects—even within an 

apparently homogeneous specimen [Dorling 

and Zussman 1987].

In the scientific literature, the term “mineral fibers” has often been used to refer not only 

to particles that occur in an asbestiform habit 

but also to particles that occur in other fibrous 

habits or as needle-like (acicular) single crystals. The term “mineral fibers” has sometimes 

also encompassed other prismatic crystals and 

cleavage fragments that meet specified dimensional criteria. Cleavage fragments are generated by crushing and fracturing minerals, including the nonasbestiform analogs of the 

asbestos minerals. Although the substantial 

hazards of inhalational exposure to airborne 

asbestos fibers have been well documented, 

there is ongoing debate about whether exposure to thoracic-size EMPs (EMPs of a size that 

can enter the thoracic airways when inhaled) 

from nonasbestiform analogs of the asbestos 

minerals is also hazardous.

2.3 Terminology

The use of nonstandard terminology or terms 

with imprecise definitions when reporting 

studies makes it difficult to fully understand 

the implications of these studies or to compare 

the results to those of other studies. For the 

health community, this ultimately hampers research efforts, leads to ambiguity in exposureresponse relationships, and could also lead to 

imprecise recommendations to protect human 

health. Terms are often interpreted differently 

between disciplines. The situation is complicated by further different usage of the same terms 

by stakeholders outside of the scientific community. NIOSH has carefully reviewed numerous resources and has not found any current 

reference for standard terminology and definitions in several disciplines that is complete 

and unambiguous. An earlier tabulation of asbestos-related terminology by the USGS demonstrated similar issues [Lowers and Meeker 

2002]. The terms “asbestos” and “asbestiform” 

exemplify this issue. They are commonly used 

terms but lack mineralogical precision. “Asbestos” is a term used for certain minerals that 

have crystallized in a particular macroscopic 

habit with certain commercially useful properties. These properties are less obvious on microscopic scales, and so a different definition of 

“asbestos” may be necessary at the scale of the 

light microscope or electron microscope, involving characteristics such as chemical composition and crystallography. “Asbestiform” is 

a term applied to minerals with a macroscopic 

habit similar to that of asbestos. The lack of precision in these terms and the difficulty in translating macroscopic properties to microscopically identifiable characteristics contribute to 

miscommunication and uncertainty in identifying toxicity associated with various forms 

of minerals. Some deposits may contain more 

than one habit or transitional particles may be 
8 NIOSH CIB 62 • Asbestos

present, which make it difficult to clearly and 

simply describe the mineralogy. Furthermore, 

the minerals included in the term asbestos 

vary between federal agencies and sometimes 

within an agency. 

NIOSH supports the development of standard 

terminology and definitions relevant to the issues of asbestos and other EMPs that are based 

on objective criteria and are acceptable to the 

majority of scientists. NIOSH also supports 

the dissemination of standard terminology 

and definitions to the community of interested nonscientists and encourages adoption and 

use by this community. The need for the development and standardization of unambiguous 

terminology and definitions warrants a priority effort of the greater scientific community 

that should precede, or at least be concurrent 

with, further research efforts.

2.3.1 Mineralogical Definitions

The minerals of primary concern are the 

asbestiform minerals that have been regulated 

as asbestos (chrysotile, amosite,† crocidolite,‡

tremolite asbestos, actinolite asbestos, and 

anthophyllite asbestos). In addition, there is interest in closely related minerals to which workers might be exposed that (1) were not commercially used but would have been mineralogically 

identified as regulated asbestos minerals at the 

time the asbestos regulations were promulgated (e.g., asbestiform winchite and richterite); 

(2)  are other asbestiform amphiboles (e.g., 

fluoro-edenite); (3)  might resemble asbestos (e.g., fibrous antigorite); (4)  are unrelated 

EMPs (e.g., the zeolites erionite and mordenite, 

fibrous talc, and the clay minerals sepiolite and 

palygorskite); and (5)  are individual particles 

†

Amosite is not recognized as a proper mineral name.

‡

Crocidolite is not recognized as a proper mineral name.

or fragments of the nonasbestiform analogs of 

asbestos minerals. Minerals are precisely defined by their chemical composition and crystallography. Ionic substitutions occur in minerals, especially for metal cations of similar ionic 

charge or size. Such substitution can result in 

an isomorphous series (also referred to as solidsolution or mixed crystal) consisting of minerals of varying composition between end-members with a specific chemical composition. The 

differences in chemical composition within an 

isomorphous series can result in different properties such as color and hardness, as well as differences in crystal properties by alteration of 

unit-cell dimensions. It is sometimes possible 

to differentiate mineral species on the basis of 

distinctive changes through an isomorphous series. However, in general, classification occurs 

by an arbitrary division based on chemistry, 

and this can be complicated by having multiple 

sites of possible substitution (e.g., in a specific 

mineral, calcium may exchange for magnesium 

in one position whereas sodium and potassium 

may be exchanged in another position). These 

allocations are open to reevaluation and reclassification over time (e.g., the mineral now 

named richterite was called soda-tremolite in 

pre-1978 IMA nomenclature).

When certain minerals were marketed or regulated as asbestos, the mineral names had definitions that might have been imprecise at the time 

and might have changed over time. In particular, the mineral name amosite was a commercial 

term for a mineral that was not well defined at 

first. The definitions of amosite in the Dictionary 

of Mining, Mineral, and Related Terms [USBOM 

1996] and in the Glossary of Geology [American 

Geological Institute 2005] allow for the possibility that amosite might be anthophyllite asbestos, although it is now known to be a mineral in 

the cummingtonite-grunerite series. This is one 

source of confusion in the literature.
NIOSH CIB 62 • Asbestos 9

A further source of confusion comes from the 

use of the geological terms for a mineral habit. 

Minerals of the same chemistry differing only 

in the expression of their crystallinity (e.g., massive, fibrous, asbestiform, or prismatic) are not 

differentiated in geology as independent species. Thus, tremolite in an asbestiform crystal 

habit is not given a separate name (either chemical or common) from tremolite in a massive 

habit. It has been suggested that crystals grown 

in an “asbestiform” habit can be distinguished 

by certain characteristics, such as parallel or radiating growth of very thin and elongate crystals that are to some degree flexible, the presence of bundles of fibrils, and, for amphiboles, 

a particular combination of twinning, stacking 

faults, and defects [Chisholm 1973]. The geological conditions necessary for the formation 

of asbestiform crystals are not as common as 

those that produce other crystal habits. These 

other habits may occur without any accompanying asbestiform crystals. However, amphibole asbestos may also include additional amphiboles that, if separated, are not asbestiform 

[Brown and Gunter 2003]. The mineralogical community uses many terms, including fibril, fiber, fibrous, acicular, needlelike, prismatic, and columnar, to denote crystals that are 

elongate. In contrast, in sedimentology, similar 

terms have been more narrowly defined with 

specific axial ratios.

Thus it is not clear, even from a single reference 

source, exactly what range of morphologies are 

described by these terms and the degree of 

overlap, if any. For example, the Dictionary of 

Mining, Mineral, and Related Terms defines fibril as “a single fiber, which cannot be separated into smaller components without losing its 

fibrous properties or appearance,” but also defines a fiber as “the smallest single strand of asbestos or other fibrous material.”

2.3.2 Other Terms and Definitions

Health-related professions also employ terminology that can be used imprecisely. For example, the terms “inhalable” and “respirable” have 

different meanings but are sometimes used interchangeably. Also, each of these terms is defined somewhat differently by various professional organizations and agencies. Particles can 

enter the human airways, but the aspiration efficiency, the degree of penetration to different 

parts of the airways, and the extent of deposition depend on particle aerodynamics, as well 

as on the geometry and flow dynamics within 

the airways. In addition to obvious differences 

between species (e.g., mouse, rat, dog, primate, 

human), there is a significant range of variation 

within a species based on, for example, age, sex, 

body mass, and work-rate. Thus, these terms 

may mean different things to a toxicologist engaging in animal inhalation experiments, an 

environmental specialist concerned with childhood exposure, and an industrial hygienist 

concerned with adult, mostly male, workers.

2.4 Trends in Asbestos Use, 

Occupational Exposures, 

and Disease

2.4.1 Trends in Asbestos Use

Over recent decades, mining and use of asbestos have declined in the United States. The 

mining of asbestos in the United States ceased 

in 2002. Consumption of raw asbestos continues to decline from a peak of 803,000 metric 

tons in 1973 [USGS 2006]. In 2006, 2000 metric tons of raw asbestos were imported, down 

from an estimated 35,000 metric tons in 1991 

(see Figure 1) and a peak of 718,000 metric 

tons in 1973. Unlike information on the importation of raw asbestos, information is not 
10 NIOSH CIB 62 • Asbestos

readily available on the importation of asbestoscontaining products. The primary recent uses 

for asbestos materials in the United States are 

estimated as 55% for roofing products, 26% for 

coatings and compounds, and 19% for other 

applications [USGS 2007], and more recently 

as 84% for roofing products and 16% for other 

applications [USGS 2008]. 

Worldwide, the use of asbestos has declined. 

Using the amount of asbestos mined as a surrogate for the amount used, worldwide annual use has declined from about 5 million metric tons in 1975 to about 2 million metric tons 

since 1999 [Taylor et al. 2006]. The European 

Union has banned imports and the use of asbestos with very limited exceptions. In other regions of the world, there is a continued 

demand for inexpensive, durable construction materials. Consequently, markets remain 

strong in some countries for asbestos-cement 

products, such as asbestos-cement panels for 

construction of buildings and asbestos-cement 

pipe for water-supply lines. Currently over 70% 

of all mined asbestos is used in Eastern Europe 

and Asia [Tossavainen 2005].

Historically, chrysotile accounted for more 

than 90% of the world’s mined asbestos; it 

presently accounts for over 99% [Ross and 

Virta 2001; USGS 2008]. Mining of crocidolite 

(asbestiform riebeckite) and amosite (asbestiform cummingtonite-grunerite) deposits have 

accounted for most of the remaining asbestos. 

Mining of amosite is thought to have ceased in 

1992 and mining of crocidolite is thought to 

have ended in 1997, although it is not possible 

to be certain. Small amounts of anthophyllite 

asbestos have been mined in Finland [Ross and 

Virta 2001] and are currently being mined in 

India [Ansari et al. 2007].

2.4.2 Trends in Occupational Exposure

Since 1986, the annual geometric mean concentrations of occupational exposures to asbestos in 

the United States, as reported in the Integrated 

Management Information System (IMIS) of the 

Occupational Safety and Health Administration 

Figure 1. U.S. asbestos production and imports, 1991–2007. Source of data: USGS [2008].
NIOSH CIB 62 • Asbestos 11

(OSHA) and the database of the Mine Safety 

and Health Administration (MSHA), have been 

consistently below the NIOSH recommended exposure limit (REL) of 0.1 fibers per cubic 

centimeter of air (f/cm3

) for all major industry divisions (Figure 2). The number of occupational asbestos exposures that were measured 

and reported in IMIS decreased from an average of 890 per year during the 8-year period of 

1987–1994 to 241 per year during the 5-year period of 1995–1999 and 135 for the 4-year period of 2000–2003. The percentage exceeding the 

NIOSH REL decreased from 6.3% in 1987–1994 

to 0.9% in 1995–1999, but it increased to 4.3% in 

2000–2003. During the same three periods, the 

number of exposures measured and reported in 

MSHA’s database decreased from an average of 

47 per year during 1987–1994 to an average of 

23 per year during 1995–1999, but it increased 

to 84 during 2000–2003 (most of which were 

collected in 2000). The percentage exceeding 

the NIOSH REL decreased from 11.1% in 1987–

1994 to 2.6% in 1995–1999, but it increased to 

9.8% in 2000–2003 [NIOSH 2007a]. 

The preceding summary of occupational exposures to asbestos is based on the OSHA and 

MSHA regulatory definitions relating to asbestos. 

Because NIOSH includes nonasbestiform analogs of the asbestos minerals in the REL that may 

have, at least from some samples, been excluded 

by OSHA and MSHA in performing differential 

counting, the reported percentages of exposures 

exceeding the REL should be interpreted as lower limits. Because of analytical limitations of the 

phase contrast microscopy (PCM) method and 

the variety of workplaces from which the data 

were obtained, it is unclear what portions of these 

exposures were to EMPs from nonasbestiform 

analogs of the asbestos minerals, which have 

been explicitly encompassed by the NIOSH REL 

for airborne asbestos fibers since 1990.

Figure 2. Asbestos: Annual geometric mean exposure concentrations by major industry division, 

MSHA and OSHA samples, 1979–2003. Source of data: NIOSH [2007a]. Note: the MSHA PEL for 

this time period was 2 f/cm3

.
12 NIOSH CIB 62 • Asbestos

Very limited information is available on the 

number of workers still exposed to asbestos. 

On the basis of mine employment data [MSHA 

2002], NIOSH estimated that 44,000 miners 

and other mine workers may be exposed to asbestos or amphibole cleavage fragments during the mining of some mineral commodities 

[NIOSH 2002]. OSHA estimated in 1990 that 

about 568,000 workers in production and services industries and 114,000 in construction 

industries may be exposed to asbestos in the 

workplace [OSHA 1990]. More recently, OSHA 

has estimated that 1.3 million employees in construction and general industry face significant 

asbestos exposure on the job [OSHA 2008].

In addition to evidence from OSHA and MSHA 

that indicates a reduction in occupational exposures in the United States over the last several decades of the 1900s, other information 

compiled on workplace exposures to asbestos indicates that the nature of occupational 

exposures to asbestos has changed [Rice and 

Heineman 2003]. Once dominated by chronic exposures in manufacturing processes such 

as those used in textile mills, friction product 

manufacturing, and cement pipe fabrication, 

current occupational exposures to asbestos in 

the United States primarily occur during maintenance activities or remediation of buildings 

containing asbestos. These current occupational exposure scenarios frequently involve 

short-term, intermittent exposures.

2.4.3 Trends in Asbestos-related 

Disease

Evidence that asbestos causes lung cancer and 

mesothelioma in humans is well documented 

[NIOSH 1976; IARC 1977, 1987a,b; EPA 1986; 

ATSDR 2001; HHS 2005a]. Epidemiological 

studies of workers occupationally exposed to 

asbestos have clearly documented a substantial 

increase in risk of several nonmalignant respiratory diseases, including diffuse fibrosis of the 

lung (i.e., asbestosis) and nonmalignant pleural abnormalities including acute pleuritis and 

chronic diffuse and localized thickening of the 

pleura [ATS 2004]. In addition, it has been determined that laryngeal cancer [IOM 2006] and 

ovarian cancer [Straif et al. 2009] can be caused 

by exposure to asbestos, and evidence suggests 

that asbestos may also cause other diseases (e.g., 

pharyngeal, stomach, and colorectal cancers 

[IOM 2006] and immune disorders [ATSDR 

2001]).

National surveillance data, showing trends over 

time, are available for two diseases with rather 

specific mineral fiber etiologies—asbestosis and 

malignant mesothelioma (see following subsections). Lung cancer is known to be caused in 

part by asbestos fiber exposure but has multiple etiologies. Ongoing national surveillance for 

lung cancer caused by asbestos exposure has not 

been done. However, using various assumptions 

and methods, several researchers have projected 

the number of U.S. lung cancer deaths caused by 

asbestos. Examples of the projected number of 

asbestos-caused lung cancer deaths in the United States include 55,100 [Walker et al. 1983] and 

76,700 [Lilienfeld et al. 1988]; each of these projections represent the 30-year period from 1980 

through 2009. However, in the absence of specific diagnostic criteria and a specific disease 

code for the subset of lung cancers caused by asbestos, ongoing surveillance cannot be done for 

lung cancer caused by asbestos.

 2.4.3.1 Asbestosis

NIOSH has annually tracked U.S. deaths due to 

asbestosis since 1968 and deaths due to malignant mesothelioma since 1999, using death certificate data in the National Occupational Respiratory Mortality System (NORMS). NORMS 
NIOSH CIB 62 • Asbestos 13

data, representing all deaths among U.S. residents, show that asbestosis deaths increased almost 20-fold from the late 1960s to the late 1990s 

(Figure 3) [NIOSH 2007b]. Asbestosis mortality 

trends are expected to substantially trail trends 

in asbestos exposures (see Section 2.4.2) for two 

primary reasons: (1) the latency period between 

asbestos exposure and asbestosis onset is typically long, commonly one or two decades or 

more; and (2) asbestosis is a chronic disease, so 

affected individuals can live for many years with 

the disease before succumbing. In fact, asbestosis deaths have apparently plateaued (at nearly 

1,500 per year) since 2000 (Figure 3) [NIOSH 

2007b]. Ultimately, it is anticipated that the annual number of asbestosis deaths in the United 

States will decrease substantially as a result of 

documented reductions in exposure. However, 

asbestos use has not been completely eliminated, and because asbestos-containing materials 

remain in structural materials and machinery, 

the potential for exposure continues. Thus, 

asbestosis deaths in the United States are anticipated to continue for several decades.

2.4.3.2 Malignant Mesothelioma

Malignant mesothelioma, an aggressive disease 

that is nearly always fatal, is known to be caused 

by exposure to asbestos and some other mineral fibers [IOM 2006]. The occurrence of 

mesothelioma has been strongly linked with 

occupational exposures to asbestos [Bang et 

al. 2006]. There had been no discrete International Classification of Disease (ICD) code for 

mesothelioma until its most recent 10th revision. 

Thus, only seven years of NORMS data are available with a specific ICD code for mesothelioma 

(Figure 4); during this period, there was a 9% 

increase in annual mesothelioma deaths, from 

2,484 in 1999 to 2,704 in 2005 [NIOSH 2007b]. 

A later peak for mesothelioma deaths than 

for asbestosis deaths would be entirely expected, given the longer latency for mesothelioma 

Figure 3. Number of asbestosis deaths, U.S. residents aged ≥15 years, 1968–2004. Source of data: 

NIOSH [2007b].
14 NIOSH CIB 62 • Asbestos

[Järvholm et al. 1999]. One analysis of malignant mesothelioma incidence based on the National Cancer Institute’s Surveillance, Epidemiology, and End Results (SEER) Program data 

found that an earlier steep increase in incidence had moderated and that mesothelioma 

incidence may have actually peaked sometime 

in the 1990s in SEER-covered areas [Weill et al. 

2004]. In contrast to NORMS data, which represents a census of all deaths in the entire United States, the analyzed SEER data were from areas in which a total of only about 15% of the U.S. 

population resides.

2.5 Workers’ Home 

Contamination 

In addition to workers’ exposures, their families 

also have the potential for exposure to asbestos 

[NIOSH 1995]. Families have been exposed to 

asbestos when workers were engaged in mining, shipbuilding, insulating, maintenance and 

repair of boilers and vehicles, and asbestos removal operations. Occupants of homes where 

asbestos workers live may be exposed while 

house cleaning and laundering; these activities 

can result in hazardous exposure for the person performing the tasks, as well as for others 

in the household. 

As the understanding of the effects of secondhand exposure to asbestos has increased, health 

effects among families of asbestos-exposed 

workers have been identified. Most documented cases of asbestos-related disease among 

workers’ family members have occurred in 

households where women were exposed during 

home laundering of contaminated work clothing. In addition, children have been exposed 

Figure 4. Number of deaths due to malignant mesothelioma, U.S. residents aged ≥15 years, 1999–

2005. Source of data: NIOSH [2007b].
NIOSH CIB 62 • Asbestos 15

at home by playing in areas where asbestoscontaminated shoes and work clothes were located, or where asbestos-containing materials 

were stored [NIOSH 1995]. As a result of these 

exposures, family members have been found to 

be at increased risk of malignant mesothelioma, 

lung cancer, cancer of the gastrointestinal tract, 

asbestosis, and nonmalignant pleural abnormalities [NIOSH 1995].

Because of the long latency periods between 

exposure and manifestation of asbestos-related disease, identification and intervention are 

difficult. Home contamination may pose a serious public health problem; however, the extent to which these health effects occur is not 

fully known because there are no information 

systems to track them [NIOSH 1995].

2.6 Clinical Issues

A thorough review of how asbestos-related diseases are diagnosed is beyond the scope of this 

document, and authoritative guidance on the 

diagnosis and attribution of asbestos-caused 

diseases has been published elsewhere [Anonymous 1997; British Thoracic Society Standards of Care Committee 2001; Henderson et 

al. 2004; ATS 2004].

The diagnosis of asbestos-caused malignancies 

(e.g., lung cancer and malignant mesothelioma) 

is almost always based on characteristic histology (or abnormal cytology in some cases). Despite research on other possible etiologies, genetic susceptibilities, and hypothesized cofactors 

such as simian virus 40, it is generally accepted 

that most cases of malignant mesothelioma are 

caused by exposure to asbestos or other mineral (e.g., erionite) fibers [Robinson and Lake 

2005; Carbone and Bedrossian 2006]. Of particular concern to patients diagnosed with malignant mesothelioma, as well as to individuals 

who remain at risk due to past exposures, the 

disease currently is essentially incurable [British 

Thoracic Society Standards of Care Committee 

2001]. Diagnosis may be relatively straightforward but can be difficult because of a challenging differential diagnosis [Lee et al. 2002]. Advances have been made to improve diagnostic 

testing for malignant mesothelioma with use of 

immunochemical markers and other more sophisticated histopathological analyses, and additional research is aimed at improving treatment of the disease [Robinson and Lake 2005]. 

Notable recent research efforts have been directed toward the development of biomarkers for 

mesothelioma that can be assessed by noninvasive means. A long-term goal of the biomarker 

research is to enable screening of high-risk individuals with sufficiently sensitive and specific noninvasive biomarkers to identify disease 

at an early stage, when therapeutic intervention might have a greater potential to slow the 

progression of the disease or be curative. Other goals are to use noninvasive biomarkers for 

monitoring the disease in patients treated for 

mesothelioma and for diagnosing the disease. 

Noninvasive biomarkers, including osteopontin 

and soluble mesothelin-related peptide, have 

been and continue to be evaluated, but none are 

considered ready for routine clinical application 

[Cullen 2005; Scherpereel and Lee 2007].

Nonmalignant asbestos-related diseases are diagnosed by considering three major necessary 

criteria: (1) evidence of structural change consistent with asbestos-caused effect (e.g., abnormality on chest image and/or tissue histology); (2)  evidence of exposure to asbestos 

(e.g., history of occupational or environmental exposure with appropriate latency, and/

or higher than normal numbers of asbestos bodies identified in lung tissue, sputum, 

or bronchoalveolar lavage; and/or other concurrent marker of asbestos exposure, such as 
16 NIOSH CIB 62 • Asbestos

pleural plaques as evidence of exposure when 

diagnosing asbestosis); and (3) exclusion of alternative diagnoses [ATS 2004]. The specificity of an asbestosis diagnosis increases as the 

number of consistent clinical abnormalities increases [ATS 2004]. In practice, only a small 

proportion of cases are diagnosed on the basis of tissue histopathology, as lung biopsy is an 

invasive procedure with inherent risks for the 

patient. Thus, following reasonable efforts to 

exclude other possible diagnoses, the diagnosis 

of asbestosis usually rests on chest imaging abnormalities that are consistent with asbestosis 

in an individual judged to have sufficient exposure and latency since first exposure.

Chest radiography remains the most commonly used imaging method for screening exposed individuals for asbestosis and for evaluating symptomatic patients. Nevertheless, as 

with any screening tool, the predictive value of 

a positive chest radiograph alone depends upon 

the underlying prevalence of asbestosis in the 

screened population [Ross 2003]. A widely accepted system for classifying radiographic abnormalities of the pneumoconioses was initially intended primarily for epidemiological use 

but has long been widely used for other purposes (e.g., to determine eligibility for compensation and for medicolegal purposes) [ILO 2002]. 

A NIOSH-administered “B Reader” Program 

trains and tests physicians for proficiency in 

the application of this system [NIOSH 2007c]. 

Some problems with the use of chest radiography for pneumoconioses have long been recognized [Wagner et al. 1993] and recent abuses have garnered substantial attention [Miller 

2007]. In response, NIOSH recently published 

guidance for B Readers [NIOSH 2007d] and for 

the use of B Readers and ILO classifications in 

various settings [NIOSH 2007e].

In developed countries, conventional film radiography is rapidly giving way to digital radiography, and work is currently under way to 

develop digital standards and validate their use 

in classifying digital chest radiographs under 

the ILO system [Franzblau et al. 2009; NIOSH 

2008a]. Progress on developing technical standards for digital radiography done for pneumoconiosis and ILO classification is under 

way [NIOSH 2008a]. In a validation study involving 107 subjects with a range of chest parenchymal and pleural abnormalities typical of 

dust-induced diseases, Franzblau et al. [2009] 

compared ILO classifications based on digital 

radiographic images and corresponding conventional chest X-ray films. The investigators 

found no difference in classification of small 

parenchymal opacities. Minor differences were 

observed in the classification of large parenchymal opacities, though more substantial differences were observed in the classification of 

pleural abnormalities typical of asbestos exposure [Franzblau et al. 2009]. 

Computerized tomography, especially highresolution computed tomography (HRCT), 

has proven more sensitive and more specific than chest radiography for the diagnosis of 

asbestosis and is frequently used to help rule 

out other conditions [DeVuyst and Gevenois 

2002]. Standardized systems for classifying 

pneumoconiotic abnormalities have been proposed for computed tomography but have not 

yet been widely adopted [Kraus et al. 1996; 

Huuskonen et al. 2001]. 

In addition to documenting structural tissue changes consistent with asbestos-caused 

disease, usually assessed radiographically 

as discussed above, the diagnosis of asbestosis relies on documentation of exposure 

[ATS 2004]. In clinical practice, exposure 

is most often ascertained by the diagnosing 
NIOSH CIB 62 • Asbestos 17

physician from an occupational and environmental history, assessed with respect to intensity and duration. Such a history enables 

a judgment about whether the observed clinical abnormalities can be reasonably attributed to past asbestos exposure, recognizing 

that severity of lung fibrosis is related to dose 

and latency [ATS 2004]. The presence of 

otherwise unexplained characteristic pleural plaques, especially if calcified, can also be 

used as evidence of past asbestos exposure 

[ATS 2004]. As explained by the ATS [2004], 

“the specificity of the diagnosis of asbestosis increases with the number of consistent 

findings on chest film, the number of clinical features present (e.g., symptoms, signs, 

and pulmonary function changes), and the 

significance and strength of the history of 

exposure.” In a small minority of cases, particularly when the exposure history is uncertain or vague or when additional clinical assessment is required to resolve a challenging 

differential diagnosis, past asbestos exposure 

is documented through mineralogical analysis of sputum, bronchoalveolar lavage fluid, 

or lung tissue. Light microscopy can be used 

to detect and count asbestos bodies (i.e., asbestos fibers that have become coated with 

iron-containing hemosiderin during residence in the body, more generically referred 

to as ferruginous bodies) in clinical samples. Electron microscopy (EM) can be used 

to detect and count uncoated asbestos fibers 

in clinical samples. Methods for such clinical 

mineralogical analyses often vary, and valid 

background levels are difficult to establish. 

The absence of asbestos bodies cannot be 

used to rule out past exposure with certainty, particularly chrysotile exposure, because 

chrysotile fibers are known to be less persistent in the lungs than amphibole asbestos 

fibers and are less likely to produce asbestos 

bodies [De Vuyst et al. 1998; ATS 2004].

2.7 The NIOSH 

Recommendation for 

Occupational Exposure 

to Asbestos 

NIOSH has determined that exposure to asbestos fibers causes cancer and asbestosis in 

humans and recommends that exposures be 

reduced to the lowest feasible concentration. 

NIOSH has designated asbestos to be a “Potential Occupational Carcinogen”§

. Currently, the 

designation “Potential Occupational Carcinogen” is based on the classification system adopted by OSHA in the 1980s and is the only 

designation NIOSH uses for occupational carcinogens. After initially setting an REL at 2 asbestos fibers per cubic meter of air (f/cm3

) in 

1972, NIOSH later reduced its REL to 0.1 f/cm3, 

measured as an 8-hour time-weighted average 

(TWA)¶ [NIOSH 1976]. The REL was set at a 

§

NIOSH’s use of the term “Potential Occupational Carcinogen” dates to the OSHA classification outlined in 

29 CFR 1990.103, and, unlike other agencies, is the 

only classification for carcinogens that NIOSH uses. 

See Section 6.1 for the definition of “Potential Occupational Carcinogen.” The National Toxicology Program [NTP 2005], of which NIOSH is a member, has 

determined that asbestos and all commercial forms of 

asbestos are known to be human carcinogens based on 

sufficient evidence of carcinogenicity in humans. The 

International Agency for Research on Cancer (IARC) 

concluded that there was sufficient evidence for the carcinogenicity of asbestos in humans [IARC 1987b]. ¶

The averaging time for the REL was later changed to 100 

minutes in accordance with NIOSH Analytical Method #7400 [NIOSH 1994a]. This change in sampling 

time was first mentioned in comments and testimony 

presented by NIOSH to OSHA [NIOSH 1990a,b] and 

was reaffirmed in comments to MSHA in 2002, with 

the explanation that the 100-minute averaging time 
18 NIOSH CIB 62 • Asbestos

level intended to (1) protect against the noncarcinogenic effects of asbestos; (2)  materially reduce the risk of asbestos-induced cancer (only a ban can ensure protection against 

carcinogenic effects of asbestos); and (3)  be 

measured by techniques that are valid, reproducible, and available to industry and official 

agencies [NIOSH 1976]. This REL was set at 

the limit of quantification (LOQ) for the phase 

contrast microscopy (PCM) analytical method 

for a 400-L sample, but risk estimates indicated 

that exposure at 0.1 f/cm3 throughout a working lifetime would be associated with a residual risk for lung cancer. A risk-free level of exposure to airborne asbestos fibers has not been 

established [NIOSH 1976, 1984].

2.7.1 The NIOSH REL as Revised 

in 1990

In 1990, NIOSH [1990b] revised its REL, retaining the 0.1 f/cm3

 limit but explicitly encompassing EMPs from the nonasbestiform analogs of 

the asbestos minerals:

NIOSH has attempted to incorporate the 

appropriate mineralogic nomenclature in 

its recommended standard for asbestos and 

recommends the following to be adopted 

for regulating exposures to asbestos:

The current NIOSH asbestos recommended exposure limit is 100,000 fibers greater 

than 5 micrometers in length per cubic meter of air, as determined in a sample collected over any 100-minute period at a flow rate 

of 4 L/min using NIOSH Method 7400, or 

equivalent. In those cases when mixed fiber types occur in the same environment, 

would help “to identify and control sporadic exposures 

to asbestos and contribute to the overall reduction of 

exposure throughout the workshift” [NIOSH 2002].

then Method 7400 can be supplemented 

with electron microscopy, using electron diffraction and microchemical analyses to improve specificity of the fiber determination. 

NIOSH Method 7402 ... provides a qualitative technique for assisting in the asbestos fiber determinations. Using these NIOSH microscopic methods, or equivalent, airborne 

asbestos fibers are defined, by reference, as 

those particles having (1) an aspect ratio of 

3 to 1 or greater; and (2)  the mineralogic 

charz elemental composition) of the asbestos minerals and their nonasbestiform analogs. The asbestos minerals are defined as 

chrysotile, crocidolite, amosite (cummingtonite-grunerite), anthophyllite, tremolite, 

and actinolite. In addition, airborne cleavage fragments from the nonasbestiform habits of the serpentine minerals antigorite and 

lizardite, and the amphibole minerals contained in the series cummingtonite-grunerite, 

tremolite-ferroactinolite, and glaucophaneriebeckite shall also be counted as fibers provided they meet the criteria for a fiber when 

viewed microscopically.

The NIOSH REL for asbestos has been described in NIOSH publications and in formal 

comments and testimony submitted to the Department of Labor. The recommendation was 

based on the Institute’s understanding in 1990 

of potential hazards, the ability of the analytical methods to distinguish and count fibers, 

and the prevailing mineral definitions used to 

describe covered minerals.

2.7.1.1 Rationale for Encompassing 

Nonasbestiform Analogs of 

Asbestos Varieties Within the REL

NIOSH’s rationale for recommending that nonasbestiform analogs of the asbestos minerals 

be encompassed within the policy definition 
NIOSH CIB 62 • Asbestos 19

of airborne asbestos fibers was first articulated 

in comments and testimony to OSHA [NIOSH 

1990a,b]. According to the 1990 testimony, 

NIOSH based its recommendation on three 

elements:

• The first element comprised results of

epidemiological studies of worker populations exposed to EMPs from nonasbestiform mineral analogs of the asbestos varieties (e.g., cleavage fragments). The 1990 

testimony characterized the existing evidence as equivocal for excess lung cancer risk attributable to exposure to such 

nonasbestiform EMPs.

• The second element comprised results of 

animal carcinogenicity studies involving 

experimental intrapleural or intraperitoneal 

administration of various mineral particles. 

The 1990 testimony characterized the results of the studies as providing strong evidence that carcinogenic potential depends 

on a mineral particle’s length and width and 

reasonable evidence that neither chemical 

composition nor mineralogical origin is a 

critical factor in determining a mineral particle’s carcinogenic potential.

• The third element comprised the lack of 

routine analytical methods to accurately 

and consistently distinguish between asbestos fibers and nonasbestiform EMPs 

in samples of airborne fibers. The 1990 

testimony argued that asbestiform and 

nonasbestiform minerals can occur in 

the same area and that determining the 

location and identification of tremolite 

asbestos, actinolite asbestos, and anthophyllite asbestos within deposits of their 

nonasbestiform mineral analogs can be 

difficult, resulting in mixed exposures 

for some mining operations and downstream users of their mined commodities.

Given the inconclusive epidemiological evidence 

for lung cancer risk associated with exposure to 

cleavage fragments (first bullet, above), NIOSH 

took a precautionary approach and relied upon 

the other two elements to recommend that the 

0.1 f/cm3 REL for airborne asbestos fibers also 

encompass EMPs from the nonasbestiform analogs of the asbestos minerals. In fact, the 1990 

NIOSH testimony included an explicit assertion that the potential risk of lung cancer from 

exposure to EMPs (of the nonasbestiform asbestos analog minerals) warranted limiting such exposures. However, even if such EMPs were not 

hazardous, the inability of analytical methods to 

accurately distinguish countable particles as either asbestos fibers or cleavage fragments (of 

the nonasbestiform analog minerals) presents a 

problem in the context of potentially mixed exposures (i.e., asbestos fibers together with EMPs 

from the nonasbestiform analogs). NIOSH’s 1990 

recommendation provided a prudent approach 

to mixed dust environments with potential exposure to asbestos; limiting the concentration of all 

countable particles that could be asbestos fibers 

to below the REL would ensure that the asbestos 

fiber component of that exposure would not exceed the REL.

Some scientists and others have questioned 

NIOSH’s rationale for including EMPs from 

nonasbestiform amphibole minerals in its 

definition of “airborne asbestos fibers.” Mineralogists argue that these EMPs do not have the 

morphological characteristics required to meet 

the mineralogical definition of “fibers”; acicular 

and prismatic amphibole crystals and cleavage fragments generated from the massive habits of the nonasbestiform analogs of the asbestos 

minerals are not true mineralogical fibers. Others have opined that the scientific literature does 
20 NIOSH CIB 62 • Asbestos

not demonstrate any clear health risks associated 

with exposure to the nonasbestiform EMPs covered by the NIOSH “airborne asbestos fiber” definition.

Whether or not to include EMPs from nonasbestiform analogs of the asbestos minerals 

in federal regulatory asbestos policies has been 

the subject of long-standing debate. The exposure-related toxicity and health effects associated with the various morphologies (e.g., acicular, 

prismatic) of the nonasbestiform analogs of 

the asbestos minerals continue to be a central 

point in the debate. In 1986, OSHA revised its 

asbestos standard and included nonasbestiform 

anthophyllite, tremolite, and actinolite (ATA) 

as covered minerals within the scope of the revised standard [OSHA 1986]. OSHA’s decision 

to include nonasbestiform ATA proved controversial. In a 1990 proposal to reverse this revision, OSHA [1990] noted that there were “a 

number of studies which raise serious questions 

about the potential health hazard from occupational exposure to nonasbestiform tremolite, 

anthophyllite and actinolite,” but that the “current 

evidence is not sufficiently adequate for OSHA to 

conclude that these mineral types pose a health 

risk similar in magnitude or type to asbestos.”

In the preamble to the final rule removing 

nonasbestiform ATA from its asbestos standard, OSHA [1992] stated that:

...various uncertainties in the data** and 

a body of data showing no carcinogenic effect, do not allow the Agency to perform 

qualitative or quantitative risk assessments 

concerning occupational exposures. Further, the subpopulations of nonasbestiform 

**OSHA was referring to the scientific data on which 

NIOSH based its own carcinogenic health effect recommendation to OSHA.

ATA which, based on mechanistic and toxicological data, may be associated with a 

carcinogenic effect, do not appear to present an occupational risk. Their presence in 

the workplace is not apparent from the record evidence.

In its 2005 proposed rule for asbestos, MSHA 

stated that substantive changes to its asbestos 

definition were beyond the scope of the proposed rule and chose to retain its definition of 

asbestos, which “does not include nonfibrous 

or nonasbestiform minerals” [MSHA 2005]. 

These decisions are reflected in MSHA’s final 

rule published in 2008 [MSHA 2008]. In formal comments during the rulemaking process, NIOSH agreed with MSHA’s decision not 

to modify its asbestos definition in the current 

rulemaking, stating that “NIOSH is presently re-evaluating its definition of asbestos and 

nonasbestiform minerals, and will work with 

other agencies to assure consistency to the extent possible” [NIOSH 2005]. In the interim, 

the following subsections provide more detail 

on the three elements comprising NIOSH’s rationale for recommending in 1990 that nonasbestiform analogs of the asbestos minerals be 

encompassed by the REL.

2.7.1.1.1 Epidemiological Studies

The first element of NIOSH’s rationale for recommending in 1990 that nonasbestiform analogs of the asbestos minerals be encompassed 

by the REL related to evidence from epidemiological studies.

A number of epidemiological studies have been 

conducted to evaluate the health risk to workers reported to be exposed to EMPs. Epidemiological studies have been conducted in the 

Governeur talc district of upstate New York in 
NIOSH CIB 62 • Asbestos 21

which the deposits have been reported to contain both amphibole cleavage fragments and 

transitional mineral fibers [Beard et al. 2001]. 

Differing interpretation of the analysis of these 

particles has caused considerable disagreement 

over the asbestos content of these talc deposits [Van Gosen et al. 2004]. Because of the disagreement over the classification of these mineral particles, the epidemiological studies of 

talc miners and millers in upstate New York 

are reviewed here. Additional epidemiological 

studies of worker populations with exposures 

to EMPs are also reviewed, including studies 

conducted at the Homestake gold mine in South 

Dakota and the taconite mining region of northeastern Minnesota. The findings from these investigations are reviewed in detail below.

Studies of New York Talc Miners and Millers

Workers exposed to talc†† have long been recognized to have an increased risk of developing pulmonary fibrosis, often referred to as talc 

pneumoconiosis [Siegel et al. 1943; Kleinfeld et 

al. 1955]. Talc-exposed workers have also been 

reported to have an increased prevalence of 

pleural abnormalities, including pleural thickening and pleural plaques [Siegel et al. 1943; 

Gamble et al. 1982].

Several more recent epidemiological studies and 

reviews have been conducted of workers employed in talc mines and mills in upstate New 

York [Brown et al. 1979, 1990; Kleinfeld et al. 

1967, 1974; Lamm and Starr 1988; Lamm et al. 

1988; Stille and Tabershaw 1982; Gamble 1993; 

Honda et al. 2002; Gamble and Gibbs 2008]. 

††The characteristics of talc deposits vary with location 

[Van Gosen et al. 2004]. Unless otherwise specified, 

the talc referred to in this section is restricted to the 

deposits in New York State which contain talc and 

other minerals.

Excessive rates of mesothelioma have been reported for Jefferson County, which is immediately adjacent to the Balmat, Fowler, and Edwards talc-mining areas of St. Lawrence County 

in New York [Vianna et al. 1981; Enterline and 

Henderson 1987; Hull et al. 2002]. In a study 

of all histologically confirmed mesothelioma 

cases reported to New York State’s tumor registry from 1973 to 1978, Vianna et al. [1981] 

reported six cases from Jefferson County, resulting in a mesothelioma rate for that county more than twice that of New York State (excluding New York City). In a national study 

of pleural cancer mortality (ICD-9 163) from 

1966 through 1981, Enterline and Henderson 

[1987] reported 4 mesothelioma cases in Jefferson County females (0.6 expected) and 7 

cases in Jefferson County males (1.4 expected), 

resulting in county mesothelioma rates that were 

the second and sixth highest county-specific 

rates in the nation for females and males, respectively (both p < 0.01). More recently, Hull 

et al. [2002] updated the Enterline and Henderson pleural cancer mortality analysis for 

Jefferson County, reporting 5 new male cases 

(2 expected) and 3 new female cases (0.5 expected) through 1997 and describing Jefferson County mesothelioma death rates as “5–10 

times the background rate.” A potential limitation of the Enterline and Henderson [1987] 

and Hull et al. [2002] analyses is that they relied on ICD code 163 (“malignant neoplasms 

of the pleura, mediastinum, and unspecified 

sites”) as a surrogate identification for malignant mesothelioma. That code lacked specificity and sensitivity for mesothelioma; in a study of 

Massachusetts deaths, many non-mesothelioma 

malignancies involving the pleura were assigned 

code 163 and most mesotheliomas were not assigned code 163 [Davis et al. 1992]. The more recent ICD-10 system, which has been used since 

1999 to code death certificate data in the United 
22 NIOSH CIB 62 • Asbestos

States, includes a discrete code for malignant 

mesothelioma. Based on that new ICD-10 code, 

the age-adjusted death rates (per million population) for 1999–2004 were 12.9 (based on 5 

mesothelioma deaths) for Jefferson County and 

10.9 (based on 5 mesothelioma deaths) for St. 

Lawrence County. These are similar to the overall U.S. mesothelioma death rates for this same 

period (based on a total of 15,379 mesothelioma 

deaths) of 11.5 per million [NIOSH 2007b]. 

An excess of lung cancer has also been reported following several epidemiological studies 

of New York talc mines and mills [Kleinfeld et 

al. 1967, 1974; Brown et al. 1990; Lamm and 

Starr 1988; Stille and Tabershaw 1982; Lamm 

et al. 1988; Honda et al. 2002]. The most extensive research has been conducted on workers at the talc mine and mills owned by RT 

Vanderbilt Company, Inc. (RTV), located in St. 

Lawrence County. A significant excess of mortality from nonmalignant respiratory disease 

(NMRD) has been consistently noted in these 

studies. These studies have also generally demonstrated an approximately twofold to threefold increase in lung cancer mortality among 

these workers [Brown et al. 1990; Honda et al. 

2002; Lamm et al. 1988]. The lung cancer excess has been reported to be particularly high 

among workers with more than 20 years since 

their first exposure (latency), which is a pattern consistent with an occupational etiology 

[Brown et al. 1979, 1990]. Authors of several 

studies have questioned whether the excess of 

lung cancer observed in these studies is due to 

employment at the RTV mines and mills or to 

other factors [Honda et al. 2002; Lamm et al. 

1988; Stille and Tabershaw 1982]. Attributing 

these findings to employment in the RTV mine 

is difficult because there were numerous mines 

operating in upstate New York, and the mineralogical composition of the ores varied substantially [Petersen et al. 1993]. A high smoking 

rate among the workers at the RTV mine and 

mills has been suggested as one possible explanation for the excess lung cancer mortality 

[Kelse 2005; Gamble 1993]. However, it is generally considered implausible that confounding by smoking in occupational cohort studies 

could explain such a large (i.e., about twofold 

to threefold) increase in lung cancer mortality 

[Steenland et al. 1984; Axelson and Steenland 

1988; Axelson 1989].

The most persuasive argument against a causal interpretation of these findings is that the 

lung cancer excess in this study population did 

not increase with duration and measures of exposure to dust [Lamm et al. 1988; Stille and 

Tabershaw 1982; Honda et al. 2002]. Also, the 

excess of lung cancer in this cohort has been 

reported to be limited to workers with short 

employment (<1 year) [Lamm et al. 1988] and 

to workers who have been employed in other industries where exposure to carcinogens 

may have occurred prior to their working in 

the RTV mine and mills [Lamm et al. 1988; 

Stille and Tabershaw 1982]. The latter observation could be explained by there simply being too few workers and inadequate follow-up 

of workers who have worked only at RTV to 

provide the statistical power necessary to demonstrate an increased lung cancer risk. For example, in one of the studies only 10% of the decedents were reported to have not worked in 

other industries prior to their employment at 

RTV [Stille and Tabershaw 1982].

In the most recent study of RTV miners and 

Millers, Honda et al. [2002] examined lung cancer mortality in relation to quantitative estimates 

of exposure to respirable talc dust [Oestenstad et 

al. 2002]. As in previous studies, mortality from 

lung cancer was found to be significantly elevated (standardized mortality ratio [SMR] = 2.3; 

95% confidence interval [95% CI] = 1.6–3.3), 
NIOSH CIB 62 • Asbestos 23

with the most pronounced excess of lung cancer mortality found in short-term workers (<5 

years). An exposure-response relationship was 

observed in the study between cumulative exposure to respirable dust and NMRD and pulmonary fibrosis.

One explanation that has been offered for the 

lack of exposure-response in these studies is 

that the observed excess of lung cancer was a 

result of exposures from employment prior 

to starting work at RTV. It has been suggested that many of these workers may have had 

prior employment in neighboring talc mines 

in upstate New York with similar exposures 

to talc [NIOSH 1980]. Not considering exposures at these other mines could have substantially impacted results of exposure-response 

analyses. Exposures to dust may also have been 

substantially higher in the neighboring mines 

than in the RTV mine [Kelse 2005]. Because 

RTV workers may have had exposures to dust 

in other mines, their exposures may have been 

underestimated, which could explain the observed lack of an exposure-response relationship in the epidemiological studies of RTV 

workers. There is also evidence to suggest that 

RTV workers may have been exposed to lung 

carcinogens from prior work in non-talc industries [Lamm et al. 1988].

Gamble [1993] conducted a nested case-control study of lung cancer in the RTV cohort 

to further explore whether factors unrelated 

to exposures at RTV, such as smoking and exposures from prior employment, might be responsible for the observed excess of lung cancer among RTV workers. Cases and controls 

were identified from among 710 workers who 

were employed between 1947 and 1958, and 

vital status was ascertained through 1983. All 

individuals whose underlying cause of death 

was lung cancer were included as cases (n = 22). 

Three controls (n = 66) for each case were selected from members of the cohort who had 

not died of NMRD or accidents, and they were 

matched to cases on the basis of dates of birth 

and hire. Controls were also required to have 

survived for as long as their matched case. Information on smoking and work histories was 

obtained by interviewing the case (if alive) or 

relatives. An attempt was made to verify information on previous employment by checking 

personnel records and by contacting previous 

employers. A panel of epidemiologists and industrial hygienists classified previous non-talc 

employment with regard to the probability of 

occupational exposure to a lung cancer risk.

As in previous investigations of the RTV cohort, Gamble [1993] found that the risk of lung 

cancer decreased with increasing duration of 

employment at RTV. This was true among both 

smokers and nonsmokers, and also when individuals with inadequate time since first exposure (<20 years) and short duration of employment were excluded. Lung cancer risk was also 

found to decrease with increasing probability 

of exposure to lung carcinogens from non-talc 

employment. A positive exposure-response relationship was evident when non-RTV talc exposures were included in the analysis, although 

this relationship was not statistically significant.

This study by Gamble [1993] does not provide 

support for the hypothesis that prior employment in non-talc industries was responsible 

for the excess of lung cancer observed among 

RTV workers. The author interpreted his findings as providing support for the argument 

that the excess of lung cancer was due to confounding by smoking, on the basis of the fact 

that smoking was strongly associated with lung 

cancer risk and on the observation that the 

exposure-response relationship with talc was 

more strongly negative (inverse) in analyses 
24 NIOSH CIB 62 • Asbestos

restricted to smokers than among all study 

subjects. However, it is no surprise that an association was observed between smoking and 

lung cancer, and the fact that the negative (inverse) exposure-response trend was stronger 

among smokers does not explain why the cohort as a whole experienced much higher lung 

cancer rates than expected.

Only two cases of pleural mesothelioma have 

been reported in the cohort studies of RTV 

miners and millers [Honda et al. 2002], and 

those authors reported that it was unclear 

whether these cases are attributable to exposure 

to talc at the RTV mine and mills. One of the 

individuals had worked for only a short time in 

a job with minimal talc exposure, had previously worked for many years in the construction of 

a talc mine, and had subsequently worked on 

repairing oil heating systems. The other case 

developed only 15 years after first exposure to 

RTV talc, although mesothelioma has more 

typically been observed to develop after much 

longer times from first exposure. NIOSH has 

recently received unpublished reports of additional cases of pleural mesothelioma among 

workers at RTV or its predecessor, International Talc [Abrams 2010; Maimon 2010], and 

a report of at least one worker using products 

from the mine who may also have died from 

mesothelioma [Satterley 2010]. NIOSH has also 

received unpublished observations concerning 

findings from chest radiographs RTV has obtained on its workers semiannually since 1985. 

Although pleural plaques were more frequently 

observed, the program has identified only one 

worker with irregular parenchymal opacities 

consistent with asbestosis-like disease, results 

that a consulting pulmonologist “did not find 

... to be consistent with that of a workforce exposed to asbestos” [Kelse et al. 2008]. 

Van Gosen [2007] has reported that fibrous 

varieties of talc, tremolite, and anthophyllite 

occur in the tremolite-talc deposits of the 

Governeur talc mining district of upstate New 

York. It has been debated whether the fibrous 

amphiboles in those talc ores meet the criteria of asbestos, with the debate centered on the 

complex and unusual transitional fibers composed partly of talc and partly of anthophyllite. 

NIOSH [1980] and others [Van Gosen 2006; 

Webber 2004] have reported that dust from the 

RTV mine, which is in the Governeur talc mining district, contains asbestos. In an industrial hygiene assessment conducted at RTV mines 

by NIOSH [1980], X-ray diffraction and petrographic microscopic analyses of talc product samples found them to contain 4.5%–15% 

anthophyllite (some of which was categorized 

as asbestos). In contrast, Kelse [2005] reported the percentage by weight of talc from the 

RTV mine in upstate New York as 1%–5% 

nonasbestiform anthophyllite. In airborne samples collected by NIOSH at the mine and mill 

and analyzed by TEM, 65% of the EMPs that 

were longer than 5 μm were anthophyllite and 

7% were tremolite, and much of the tremolite 

was from a nonfibrous habit [NIOSH 1980]. 

Kelse [2005] reported that up to 1.8% was from 

an asbestiform habit, though the asbestiform 

component was reported not to be asbestos. 

Serpentine and amphibole minerals typically develop through the alteration of other minerals. Consequently, they may exist as partially 

altered minerals having variations in elemental compositions. Minerals undergoing this alteration are often called “transitional minerals.” 

Thus the elemental composition of individual 

mineral particles can vary within a mineral deposit containing transitional minerals, which 

could account for differences in the reported 

composition of talc from the RTV mine.
NIOSH CIB 62 • Asbestos 25

A limitation of the epidemiological studies of 

RTV talc workers is the lack of an exposure-response analysis based on direct measurements 

of airborne EMP concentrations. Most of the 

studies used tenure as a surrogate for exposure, 

and the exposure metric used in the Honda et 

al. [2002] study was respirable dust, which may 

not be correlated with exposure to EMPs. Relationships between health outcomes and exposure to an agent of interest can be attenuated 

when a nonspecific exposure indicator is used 

as a surrogate for exposure to the agent of interest [Blair et al. 2007; Friesen et al. 2007]. Thus, 

when the exposure index used to assess the effect of EMPs is based on a surrogate measure, 

such as respirable dust, rather than on specific measurement of EMP concentrations, the 

lack of an exposure-response relationship between the exposure index and the health outcome might not accurately reflect the true risk, 

particularly where the composition of a mixed 

dust exposure varies by work area.

Finally, a cohort study of Vermont talc miners 

and millers has some relevance for interpreting 

the findings from the studies of New York talc 

workers [Selevan et al. 1979]. Airborne dust 

samples and talc bulk samples from all locations 

in the mines and mill studied were analyzed 

by X-ray diffraction or analytical EM, which 

showed the talcs to be similar in composition; 

no asbestos was detected in any of the samples. 

To determine potential differences between the 

talcs mined and milled by a company no longer in operation, seven samples of talcs were 

obtained and also analyzed by X-ray diffraction or analytical EM. These samples were reported to be free of asbestos contamination and 

the mineral composition was within the range 

of samples from then-producing operations. 

The one remaining company, no longer operating at that time, had been located in the same 

geographic area as two of the then-producing 

companies. The talc in one of the closed mines 

was reported to have had “cobblestones” of serpentine rock that were highly tremolitic. In the 

mining of this talc, these cobblestones were reported to have been avoided and/or discarded. Therefore, miners may have been exposed 

to tremolite, but it is unlikely that the millers from this company were exposed [Selevan 

1979]. Van Gosen [2004] described the talc deposits in this area as “associated spatially with 

serpentinite masses that in some areas host 

well-developed chrysotile asbestos [Bain 1942; 

Cady et al. 1963]. The alteration zone locally contains actinolite, tremolite, anthophyllite, 

and (or) cummingtonite, as described by Cady 

et al. [1963]. Zodac [1940] described ‘radiating 

masses of fibrous actinolite, which often have 

to be handled carefully as the needlelike crystals may penetrate fingers, are common on the 

dumps’ in a talc quarry near Chester, Vermont. 

The amphiboles present were not identified as 

asbestiform.

A statistically significant excess of NMRD 

mortality was observed among the millers 

(SMR = 4.1; 95% CI = 1.6–8.4), but not among 

the miners (SMR = 1.6; 95% CI = 0.20–9.6), in 

this study [Selevan 1979]. In contrast, respiratory cancer mortality was found to be significantly elevated among the miners (SMR = 4.3; 

95% CI = 1.4–10), but not among the millers 

(SMR = 1.0; 95% CI = 0.12–4.0). The authors 

suggested that their respiratory cancer findings 

might be due to non-talc exposures, such as radon progeny, because exposures to talc dust 

were higher among millers than miners. The 

pattern of excess respiratory cancer observed 

in this study is similar to that reported in studies of RTV miners and millers. It has been noted [Lamm and Starr 1988] that this provides 

evidence against the hypothesis that the lung 

cancer excess among RTV miners is caused 
26 NIOSH CIB 62 • Asbestos

by exposure to the EMPs in RTV talc, because 

these were not identified in Vermont talc.

In summary, excesses of pulmonary fibrosis 

and pleural plaques are generally recognized 

to have occurred among workers exposed to 

talc. Pleural cancer mortality rates have been 

reported to be significantly elevated in Jefferson County, adjacent to St. Lawrence County, 

where the New York talc industry has been located. However, recent death certificate data 

for 1999–2004 do not suggest a particularly high rate of mesothelioma in St. Lawrence 

County or Jefferson County. Also, aspects of 

the few cases of mesothelioma that have been 

carefully evaluated in the published studies of 

New York talc miners make it unclear whether 

the cases are attributable to employment in the 

talc industry. Lung cancer mortality has been 

consistently reported to be elevated in studies 

of New York talc miners. However, attribution 

of this excess to exposures to dust containing 

talc and other minerals has been questioned, 

because the lung cancer excess was generally 

found to be most pronounced in short-term 

workers and did not increase with cumulative exposure to talc dust. It is highly unlikely 

that chance or confounding from smoking or 

prior mining exposures fully accounts for the 

lung cancer excess observed in these studies. 

These findings may be at least partly explained 

by employment in other industries, including 

other mines in upstate New York.

Studies of Homestake Gold Miners

Three groups of investigators have conducted retrospective cohort studies of miners at 

the Homestake gold mine in South Dakota, with somewhat different and overlapping 

cohort definitions. Gillam et al. [1976] studied 440 white males who were employed as of 

1960 and who had worked underground for 

at least 5 years in the mine. McDonald et al. 

[1978] conducted a retrospective cohort study 

of 1,321 men who had retired and worked 

for at least 21 years in the mine as of 1973 

and were followed for vital status until 1974. 

Brown et al. [1986] conducted a retrospective 

cohort study of 3,328 miners who had worked 

for at least 1 year between 1940 and 1965, with 

follow-up of vital status to 1977. Follow-up of 

this same cohort was subsequently updated to 

1990 by Steenland and Brown [1995]. Exposures of potential concern at this mine include crystalline silica, radon progeny, arsenic, and nonasbestiform EMPs. The longer 

(>5  μm) nonasbestiform EMPs have been reported to be primarily cummingtonite-grunerite 

(69%), but tremolite-actinolite (15%) and other 

nonasbestiform amphibole varieties (16%) were 

also detected [Zumwalde et al. 1981]. Most of 

the EMPs observed by TEM (70%–80%) were 

shorter than 5 μm; for the entire population of 

EMPs, the geometric mean length was 3.2 μm 

and the geometric mean diameter was 0.4 μm.

There is very little evidence of an excess of 

mesothelioma in the studies of Homestake 

gold miners. One case of mesothelioma with 

“low” dust exposure was noted in the study 

by McDonald et al. [1978]. Slight excesses of 

cancer of the peritoneum (4 cases; SMR = 2.8; 

95% CI = 0.76–7.2) and other respiratory cancer (3 cases; SMR = 2.5; 95% CI = 0.52–7.4) 

were described in the most recently reported study [Steenland and Brown 1995]. These 

categories might be expected to include cases of mesothelioma; however, mesothelioma 

was not mentioned on the death certificates 

for these cases.

Significant excesses in mortality from tuberculosis and pneumoconiosis (mainly silicosis) 

were observed in all of the studies. An excess of 

respiratory cancer (10 cases: SMR = 3.7; 95% 
NIOSH CIB 62 • Asbestos 27

CI = 1.8–6.7) was noted in the earliest study, by 

Gillam et al. [1976]. Respiratory cancer mortality was not found to be elevated (34 cases; 

SMR = 1.0; 95% CI = 0.71–1.4), and there was 

only weak evidence that it increased with level of exposure, in the study by McDonald et al. 

[1978]. A slight excess of lung cancer (115 cases; SMR = 1.1; 95% CI = 0.94–1.4) was noted 

in the most recent study, in comparison with 

U.S. mortality rates [Steenland and Brown 

1995]. This lung cancer excess was more pronounced when county rates were used as the 

referent (SMR = 1.3; 95% CI = 1.0–1.5), and 

even more so when South Dakota state rates 

were used (SMR = 1.6; 95% CI = 1.3–1.9). The 

excess was also increased (versus U.S. rates; 

SMR = 1.3; 95% CI = 1.0–1.6) when the analysis was restricted to individuals with at least 

30 years of time since first exposure (latency). 

Lung cancer mortality was not found to increase with estimated cumulative exposure to 

dust in this study, though a clear exposureresponse trend was observed for pneumoconiosis. The limited available data on smoking habits indicated that miners in this cohort 

smoked slightly more than the U.S. general 

population in a 1960 survey.

Taken together, the studies of Homestake gold 

miners provide, at best, weak evidence of an excess risk of lung cancer. Although small excesses 

of lung cancer have been reported in the most recent studies of the Homestake gold miners, the increased mortality has not been found to increase 

with measures of cumulative dust exposure. The 

uncertainty of the relationship between contemporaneous dust and EMP exposures hinders the 

usefulness of historical dust measurement data 

in estimating EMP exposures [Zumwalde et al. 

1981]. Thus the lack of cancer noted in these 

studies is largely uninformative with respect to 

the hypothesis that nonasbestiform EMPs are 

associated with increased risk of respiratory diseases in this population.

Studies of Taconite Miners

There has been a long history of concern about a 

potential association between exposures associated with the taconite iron ore industry in northeastern Minnesota and the potential cancer risk. 

This concern started in 1973, when amphibole 

fibers were found in the Duluth water supply 

and were traced to tailings that had been disposed of in Lake Superior by the Reserve Mining 

Company. Extensive sampling and analysis of areas of the Peter Mitchell taconite iron ore mines 

were recently conducted by Ross et al. [2007], 

who reported finding “no asbestos fibers of any 

type” in the mines. However, they did find and 

describe fibrous ferroactinolite, fibrous ferrian 

sepiolite, fibrous grunerite-ferroactinolite, and 

fibrous actinolite in ore samples, some of which 

was very thin (<0.01 μm) with a very high aspect 

ratio. They estimated fibrous amphibole material 

to represent “a tiny fraction of one percent of the 

total rock mass of this taconite deposit” [Ross et 

al. 2007].

Several epidemiological studies have examined mortality of miners working in the taconite mines and mills of Minnesota. Higgins et al. 

[1983] published the earliest study, which examined the mortality of approximately 5,700 workers employed at the Reserve Mining Company 

between 1952 and 1976 and followed up to 1976. 

Overall mortality (SMR = 0.87) and mortality 

from respiratory cancer (15 cases; SMR = 0.84) 

were both less than expected. Respiratory cancer 

mortality was not found to be increased among 

workers with at least 15 years since first exposure (latency) and did not increase with estimated cumulative exposure to dust. The maximum 

follow-up of this cohort was 24 years, which is 
28 NIOSH CIB 62 • Asbestos

probably too short to be able to detect increased 

mortality from lung cancer or mesothelioma.

Cooper et al. [1988, 1992] have reported on the 

mortality experience of 3,431 miners and millers who were employed in the Erie or Minntac 

mines and mills for at least 3 months between 

1947 and 1958. Follow-up of the cohort, initially to 1983 [Cooper et al. 1988], was extended to 1988 in their more recent update [Cooper et al. 1992]. Comparisons were made with 

white male mortality rates for Minnesota and 

for the U.S. population. Mortality from respiratory cancer was found to be slightly less than 

expected in this study (106 cases, based on 

Minnesota rates: SMR = 0.92; 95% CI = 0.75–

1.1). Respiratory cancer mortality was close to 

the expected value (46 cases, on the basis of 

Minnesota rates: SMR = 0.99; 95% CI = 0.72–

1.3) among workers with more than 20 years 

since first exposure (latency).

A statistically significant excess of mesothelioma 

has been reported in northeastern Minnesota, the area in which the taconite mining and 

milling industry is located [MDH 2007]. In 

its most recent report, the Minnesota Department of Health (MDH) reported that a total of 159 cases occurred in this region during 

the period of 1988 to 2006. The mesothelioma 

rate for males was approximately twice the expected rate, based on the rest of the state (146 

cases: rate ratio [RR] = 2.1; 95% CI = 1.8–2.5), 

whereas the rate for females was less than expected (RR = 0.72; 95% CI = 0.38–1.2). The 

fact that the excess of mesothelioma was observed only among males strongly suggests an 

occupational etiology. In addition to the taconite industry, a plant producing asbestos ceiling tiles (Conwed Corporation) was located 

in the northeastern Minnesota region. From 

1958 to 1965 amosite was used at Conwed, and 

from 1966 to 1974 chrysotile was used [Mandel 

2008]. The MDH has initiated epidemiological studies of mesothelioma incidence among 

workers at the Conwed Corporation and at the 

iron mines in northeastern Minnesota. The records from a cohort of approximately 72,000 

iron miners and from 5,700 Conwed workers have been linked with a mesothelioma data 

registry. Between 1988 and 2007, a total of 58 

mesothelioma cases among the miners and 25 

cases among the Conwed workers were identified. Because only 3 of the 58 mesothelioma 

cases identified in the miner cohort had also 

been employed at Conwed, it is unlikely that 

the mesothelioma excess in miners could be explained by asbestos exposures during employment at the Conwed ceiling tile facility [MDH 

2007].

Brunner et al. [2008] have recently reported 

findings from an MDH study of mesothelioma 

cases occurring among iron miners between 

1988 and 1996. The job histories of the cases were reviewed for evidence of exposure to 

commercial asbestos. Mining jobs were identified from company personnel files. Nonmining 

employment information was obtained from 

worker application files, worker compensation 

records, and obituaries. Potential asbestos exposures for jobs held in the mining industry 

were identified by interviewing 350 workers, 

representing 122 occupations and 7 different 

mining companies. To estimate the probability and intensity of potential exposure to commercial asbestos in each of the jobs, an expert 

panel rated the potential for asbestos exposure 

on the basis of these interviews, available job 

descriptions from the relevant time period, 

and their knowledge of the mining environment. The job histories for 15 of 17 iron miners known to have developed mesothelioma 

were considered sufficient for the study. Eleven of these 15 were reported to have had probable exposure, 3 were reported to have possible 
NIOSH CIB 62 • Asbestos 29

exposure to commercial asbestos, and 1 did not 

have an identifiable source of exposure to commercial asbestos. The asbestos exposures were 

from nonmining jobs (4 cases), mining jobs (4 

cases), or both (6 cases). The findings from this 

study suggest that the excess of mesothelioma 

observed among taconite miners might be explained by exposure to commercial asbestos 

rather than from the nonasbestiform amphibole EMPs generated during iron ore processing. However, this was a case series and it was 

not possible to determine whether commercial asbestos exposure was different in the cases than in the cohort as a whole or in a control 

group. This study also did not include the 41 

additional mesothelioma cases that have been 

reported by the MDH since 1996 [MDH 2007].

The age-adjusted rates of deaths due to malignant mesothelioma during the period 2000–

2004 for the two counties considered to be 

in the iron range (Itasca and St. Louis Counties) are reported as 30.4 and 31.3 per million, respectively, which are 2.6 and 2.7 times 

the U.S. average [NIOSH 2009a]. Two counties (Carlton and Koochiching Counties) adjacent to the iron range counties have malignant mesothelioma rates of 55.3 and 77.5 per 

million, which are 4.8 and 6.7 times the U.S. 

average. The age-adjusted asbestosis rates during 1995–2004 were reported for only two of 

these counties: St. Louis County (7.9 per million, which is 1.3 times the U.S. average) and 

Carlton County (54.0 per million, or 8.9 times 

the U.S. average) [NIOSH 2009b].

In summary, the results from cohort mortality 

studies of taconite miners and millers in Minnesota have not provided evidence of an increased 

risk of respiratory cancer or mesothelioma. 

This appears to be somewhat in conflict with 

reports from the MDH that mesothelioma incidence is significantly elevated among males 

(but not females) in northeastern Minnesota 

and that a large number of these cases involved 

workers in the Minnesota taconite industry. 

There is some evidence that these cases could, 

at least in part, be related to exposures to commercial asbestos that occurred in or outside of 

the taconite mining industry, but further research on this question is needed. The MDH is 

currently working with researchers at the University of Minnesota School of Public Health 

on a mesothelioma case-control study, a respiratory morbidity study, and a mortality study 

of the iron miners of northeastern Minnesota 

[MDH 2007].

Summary of Epidemiological Studies of

Cohorts Exposed to Nonasbestiform EMPs

The results from studies of populations exposed to nonasbestiform EMPs do not provide 

clear answers regarding the toxicity of these 

EMPs. A number of features limit their usefulness. First, the populations in these studies were exposed to a complex mixture of particles. Although an excess of pneumoconiosis 

has been observed in the studies of Homestake 

gold miners and New York talc workers, the 

extent to which these findings are attributable 

to their exposures to nonasbestiform EMPs 

cannot be determined. A potential limitation 

of the New York talc studies is that, if the EMPs 

do include fibers from asbestiform minerals, as 

reported in the literature [NIOSH 1980; Van 

Gosen 2006; Webber 2004], it is difficult to determine whether the observed health effects 

can be attributed to them, given the heterogeneous mineral composition of exposures.

Another major limitation of these studies is that 

they lack adequate information on past exposure to EMPs. An excess of respiratory cancer 

was observed in the studies of New York talc 

workers, and a small excess was observed in the 
30 NIOSH CIB 62 • Asbestos

most recent study of Homestake gold miners. 

In both studies, the excess of respiratory cancer was not found to increase with cumulative 

exposure to dust. Relationships between health 

outcomes and exposure to an agent of interest 

can be attenuated when a nonspecific exposure indicator is used as a surrogate for exposure to that agent [Blair et al. 2007; Friesen et 

al. 2007]. Thus, when the exposure index used 

to assess the effect of EMPs is based on a surrogate measure, such as respirable dust, rather 

than on specific measurement of EMP concentrations, the lack of an exposure-response relationship between the exposure index and the 

health outcome might not accurately reflect 

the true risk, particularly where the composition of a mixed exposure varies by work area. 

Interpretation of findings from the New York 

talc studies has been further complicated by 

the employment of the workers elsewhere, including employment at other talc mines in the 

area. Lack of positive findings from exposureresponse analyses in the New York talc studies 

of RTV miners and millers could also have resulted from exposure misclassification—possible 

under-ascertainment of exposure to talc and 

other mineral particles caused by not considering exposures at neighboring talc mines or 

previous employment in the same mine under 

different ownership.

The reliability of death certificate information 

is another major limitation, particularly for the 

diagnosis of mesothelioma. Mesothelioma did 

not have a discrete ICD code until the 10th revision of the ICD, used for U.S. death certificate data only since 1999. This likely explains 

the discordance between the apparent recent 

lack of excess mesothelioma deaths in an upstate New York county adjacent to the county 

in which talc mines and mills have been located and the excess “mesothelioma” death rates 

previously reported in that county. This may 

explain the apparent contradiction between 

the lack of an excess of mesothelioma in the cohort studies of taconite miners, and the excess 

of mesothelioma that has been reported in the 

more recent studies based on a mesothelioma 

registry in northeastern Minnesota. 

Finally, the lack of information on cigarette 

smoking habits of the studied workers is a major issue in interpreting the findings for respiratory cancer in these studies. Concern about cigarette smoking in occupational cohort studies 

is generally based on the assumption that blue 

collar workers smoke more than the general 

population. However, the extent of this bias is 

generally not expected to be able to account for 

more than a 50% increase in lung cancer risk 

and is unlikely to explain the twofold to threefold risk reported in the New York talc studies. Confounding by smoking could conceivably explain the small excess of lung cancer that 

has been reported in the most recent study of 

Homestake gold miners [Steenland and Brown 

1995]. However, smoking may have introduced 

a negative bias in some of these studies. Cigarette smoking has been reported to have been 

banned in the Homestake gold mines [Brown 

et al. 1986] and in the underground taconite 

mines [Lawler et al. 1985]. Preventing workers 

from smoking at work could have negatively biased the lung cancer findings in these studies.

Because of the study limitations described 

above, the findings from these studies should 

best be viewed as providing inconclusive as 

opposed to negative evidence regarding the 

health effects associated with exposures to 

nonasbestiform EMPs. To be more informative, 

additional studies of these populations would 

need improved characterizations of exposure to 

EMPs, smoking status, and exposures associated with other employment. Additional studies 
NIOSH CIB 62 • Asbestos 31

of these populations should be pursued if these 

improvements are deemed feasible.

2.7.1.1.2 Animal Studies

The second element of NIOSH’s rationale for 

recommending in 1990 that nonasbestiform 

analogs of the asbestos minerals be encompassed by the REL is related to evidence from 

animal studies. Citing several original studies 

and reviews [Stanton et al. 1977, 1981; Wagner 

et al. 1982; Muhle et al. 1987; Pott et al. 1974, 

1987; Lippmann 1988], NIOSH [1990a] concluded that they provided evidence that fiber 

dimension (and not fiber composition) was the 

major determinant of carcinogenicity for mineral fibers, stating that

Literature reviews by Lippmann [1988] 

and Pott et al. [1987] enhance the hypothesis that any mineral particle can induce 

cancer and mesothelioma if it is sufficiently durable to be retained in the lung and if 

it has the appropriate aspect ratio and dimensions. Similarly, Wagner [1986] concluded that all mineral particles of a specific diameter and length size range may 

be associated with development of diffuse 

pleural and peritoneal mesotheliomas.

That general conclusion notwithstanding, a study 

by Smith et al. [1979] that was not cited by 

NIOSH in 1990 addressed the specific question 

of carcinogenicity of EMPs from nonasbestiform 

amphiboles. Pleural tumor induction by intrapleural (IP) injection challenge in hamsters was 

compared for various challenge materials, including two asbestiform tremolites and two 

nonasbestiform (prismatic) tremolitic talcs. In 

contrast to the two asbestiform tremolites, which 

induced tumors in 22% and 42% of challenged 

hamsters at the higher dose, no tumors resulted following challenge with either of the two 

nonasbestiform tremolites [Smith et al. 1979]. In 

its rule-making, OSHA noted several limitations 

of the study, including the small number of animals studied, the early death of many animals, 

and the lack of systematic characterization of fiber size and aspect ratio [OSHA 1992]. One of 

the nonasbestiform tremolitic talcs was later analyzed and determined to have tremolitic chemical composition and 13% “fibers,” as defined by 

a 3:1 aspect ratio [Wylie et al. 1993].

Since 1990, another carcinogenicity study of 

nonasbestiform amphibole minerals has been 

published. An IP injection study in rats used six 

samples of tremolite, including three asbestiform 

samples that induced mesothelioma in 100%, 

97%, and 97% of challenged animals [Davis et 

al. 1991]. Two nonasbestiform tremolite samples resulted in mesotheliomas in 12% and 5% 

of the animals, and the response rate of 12% was 

above the expected background rate. Another 

sample that was predominantly nonasbestiform 

but reported to contain a small amount of 

asbestiform tremolite resulted in mesothelioma 

in 67% of animals. Of note, the nonasbestiform 

material associated with the 12% mesothelioma 

incidence and this latter material contained an 

approximately equal number of EMPs longer 

than 8 μm and thinner than 0.5 μm.

Studies of in vitro assays of various biological responses, some published before and 

some after 1990, have also found relative toxicities of asbestiform and nonasbestiform 

minerals that generally parallel the differences observed in the in vivo IP injection studies of tumorigenicity [Wagner et al. 1982; 

Woodworth et al. 1983; Hansen and Mossman 

1987; Marsh and Mossman 1988; Sesko and 

Mossman 1989; Janssen et al. 1994; Mossman 

and Sesko 1990] A recent review of the literature concluded that low-aspect-ratio cleavage 
32 NIOSH CIB 62 • Asbestos

fragments of amphiboles are less potent than 

asbestos fibers [Mossman 2008].

In summary, there is more literature now than in 

1990 pertaining to differential animal carcinogenicity and toxicity of EMPs from nonasbestiform 

amphiboles (e.g., acicular crystals, prismatic 

crystals, and cleavage fragments). The number of 

studies is limited and each study has limitations, 

but they suggest that nonasbestiform amphiboles 

might pose different risks than asbestos. More 

detailed discussion of these studies, including 

discussion of important limitations of the studies, 

can be found in Section 2.8.4 of this document.

2.7.1.1.3 Analytical Limitations

The third element that served as a basis for 

NIOSH’s 1990 recommendation that nonasbestiform analogs of the asbestos minerals be encompassed by the REL was the inability to accurately and consistently distinguish asbestos fibers and 

nonasbestiform EMPs in samples of airborne 

particulate. The 1990 NIOSH testimony argued 

that asbestiform and nonasbestiform minerals 

can occur in the same geological area and that 

mixed exposures to airborne asbestos fibers and 

EMPs from the nonasbestiform analog minerals 

can occur at mining operations. The potential for 

mixed exposures can also occur downstream if 

the mined commodity contains both asbestiform 

and nonasbestiform minerals.

The 1990 NIOSH testimony further pointed 

out the lack of routine analytical methods for 

air samples that can accurately and consistently determine whether an individual EMP that 

meets the dimensional criteria of a countable 

particle is an asbestos fiber or a nonasbestiform 

EMP (e.g., acicular crystals, prismatic crystals, 

cleavage fragments).

Two analytical components of the NIOSH REL 

for airborne asbestos fibers are applied to air 

samples: the microscopic methods and the 

counting rules. The microscopic methods include the following:

• Phase contrast microscopy (PCM)—Analytical Method 7400 “A rules”—Asbestos and Other Fibers by PCM [NIOSH 

1994a] is used to count all particles that 

are longer than 5 μm and have a lengthto-width ratio equal to or greater than 3:1. 

• Transmission electron microscopy (TEM)—

Analytical Method 7402—Asbestos by 

TEM [NIOSH 1994b] is used as a supplement to the PCM method when there 

is uncertainty about the identification of 

elongate particles (EPs) that are counted. When TEM analysis is used for particle identification, only those EPs that 

are identified as “asbestos” and meet 

the dimensional criteria used by PCM 

(>0.25 μm width and >5 μm length) are 

counted as asbestos fibers. PCM counts 

can be adjusted to yield corrected asbestos fiber counts by multiplying them by 

the proportion of fibers determined by 

TEM to be asbestos.

There are several limitations of the use of PCM 

and TEM for asbestos analysis. PCM is stated to be limited to observing EPs with widths 

>0.25 μm and is not equipped for particle identification. TEM, although capable of resolving 

EPs with widths as small as 0.001 μm, frequently cannot differentiate nonasbestiform from 

asbestiform EMPs when the elemental composition is the same or when present in a heterogeneous mix of unknown particles. A potential limitation of TEM is that partial lengths of 

long fibers may not be observed because they 

intersect grid bars or lie partially outside the 

small field of view. However, this is likely to 
NIOSH CIB 62 • Asbestos 33

affect only a small number of observed particles, because very few particles are greater than 

15 μm length, as evidenced in air samples from 

textile processing [Dement et al. 2009] and mining and milling operations [Gibbs and Hwang 

1980]. A more important limitation of TEM is 

that, because only a small portion of the filter 

sample is being analyzed, airborne fiber concentrations might not be determined with certainty. Another limitation of both methods is that 

high concentrations of background dust collected on samples may interfere with fiber counting by PCM and particle identification by TEM.

Thus, the current PCM and TEM methods 

used for routine exposure assessment lack the 

capability to accurately count, size, and identify all EMPs collected on airborne samples. 

Further discussion of the analytical limitations 

and possible improvements are discussed in 

Section 2.8.

2.7.2 Clarification of the Current 

NIOSH REL

As described in the preceding sections, uncertainty remains concerning the adverse health 

effects that may be caused by nonasbestiform 

EMPs encompassed by NIOSH since 1990 in 

the REL for asbestos. Also as described in a preceding section, current analytical methods still 

cannot reliably differentiate between asbestos 

fibers and other EMPs in mixed-dust environments. NIOSH recognizes that its descriptions of 

the REL since 1990 have created confusion and 

caused many to infer that the additional covered 

minerals were included by NIOSH in its definition of “asbestos.” NIOSH wishes to make clear 

that such nonasbestiform minerals are not “asbestos” or “asbestos minerals.” NIOSH also 

wishes to minimize any potential future confusion by no longer referring to particles from the 

nonasbestiform analogs of the asbestos minerals 

as “asbestos fibers.” However, as the following 

clarified REL makes clear, particles that meet the 

specified dimensional criteria remain countable 

under the REL for the reasons stated above, even 

if they are derived from the nonasbestiform analogs of the asbestos minerals.

With use of terms defined in this Roadmap, the 

NIOSH REL is now clarified as follows:

NIOSH has determined that exposure to asbestos fibers causes cancer and asbestosis in humans and recommends that exposures be reduced to the lowest feasible concentration. 

NIOSH has designated asbestos to be a “Potential Occupational Carcinogen”‡‡ and recommends that exposures be reduced to the lowest 

feasible concentration. The NIOSH REL for airborne asbestos fibers and related elongate mineral particles (EMPs) is 0.1 countable EMP from 

one or more covered minerals per cubic centimeter, averaged over 100 minutes, where

• a countable elongate mineral particle (EMP) 

is any fiber or fragment of a mineral longer 

than 5  μm with a minimum aspect ratio 

of 3:1 when viewed microscopically with 

use of NIOSH Analytical Method 7400 (‘A’ 

rules) or its equivalent; and

‡‡NIOSH’s use of the term “Potential Occupational Carcinogen” dates to the OSHA classification outlined in 

29 CFR 1990.103, and, unlike other agencies, is the 

only classification for carcinogens that NIOSH uses. 

See Section 6.1 for the definition of “Potential Occupational Carcinogen.” The National Toxicology Program [NTP 2005], of which NIOSH is a member, has 

determined that asbestos and all commercial forms of 

asbestos are known to be human carcinogens based 

on sufficient evidence of carcinogenicity in humans. 

The International Agency for Research on Cancer 

(IARC) concluded that there was sufficient evidence 

for the carcinogenicity of asbestos in humans [IARC 

1987b].
34 NIOSH CIB 62 • Asbestos

• a covered mineral is any mineral having 

the crystal structure and elemental composition of one of the asbestos  varieties (chrysotile, riebeckite asbestos [crocidolite], cummingtonite-grunerite asbestos 

[amosite], anthophyllite asbestos, tremolite 

asbestos, and actinolite asbestos) or one of 

their nonasbestiform analogs (the serpentine minerals antigorite and lizardite, and 

the amphibole minerals contained in the 

cummingtonite-grunerite mineral series, 

the tremolite-ferroactinolite mineral series, and the glaucophane-riebeckite mineral series).

This clarification of the NIOSH REL for airborne asbestos fibers and related EMPs results in no change in counts made, as defined 

by NIOSH Method 7400 (‘A’ rules). However, 

it clarifies definitionally that EMPs included in 

the count are not necessarily asbestos fibers.

The NIOSH REL comprises two components. 

One component states the agency’s intent about 

what minerals should be covered by the REL; 

the other component describes the sampling 

and analytical methods to be used for collecting, characterizing, and quantifying exposure 

to airborne particles from the covered minerals. Each of these components of the NIOSH 

REL is discussed in detail in later subsections 

of this Roadmap.

The NIOSH REL remains subject to change 

based on research findings that shed light 

on the toxicity of nonasbestiform amphibole 

EMPs covered by the REL and on the toxicity of other EMPs outside the range of those 

minerals currently covered by the REL. In addition, because of changes by the IMA in 1978 

[Meeker et al. 2003] in how minerals (e.g., amphiboles) are identified and classified (optical microscopy to chemistry-based), a more 

extensive clarification of specific minerals covered by the NIOSH REL may be warranted. 

That more extensive clarification of covered 

minerals is beyond the scope of this Roadmap

but will be addressed through additional efforts 

by NIOSH to encompass contemporary mineralogical terminology within the REL.

2.8 EMPs Other than 

Cleavage Fragments

2.8.1 Chrysotile

Chrysotile fibers consist of aggregates of long, 

thin, flexible fibrils that resemble scrolls or 

cylinders, and the dimensions of individual 

chrysotile fibers depend on the extent to which 

the material has been manipulated. Multi-fibril 

chrysotile fibers commonly split along the fiber 

length and undergo partial dissolution within 

the lungs [NRC 1984]. Such longitudinal splitting in the lung represents one way that air sample counts may underestimate the cumulative 

dose of fibers in the lung. 

Epidemiological studies of chrysotile in Quebec mines [McDonald and McDonald 1997] 

and South Carolina textile mills [Dement et al. 

1994; Hein et al. 2007] have produced very different estimates of the risk of cancer associated with exposure to chrysotile fibers. With the 

differences in fiber concentrations accounted 

for, the exposure in the textile mills appears to 

be associated with much higher risk than exposure in the mines. Several explanations for 

the difference in lung cancer risks observed in 

these two different workplaces have been proposed. One suggested explanation is that the 

textile workers were exposed to mineral oil. 

However, this explanation does not satisfactorily explain the differences [Stayner et al. 1996]. 

Considering that the textile mill workers were 
NIOSH CIB 62 • Asbestos 35

exposed to fibers considerably longer and thinner than those found in mines [Peto et al. 1982; 

Dement and Wallingford 1990], a more likely 

explanation is that the difference in risk may 

be due, at least in part, to dimensional differences in the particles to which workers were 

exposed. It has also been proposed that exposures in the textile mills were almost exclusively to chrysotile asbestos, whereas exposures in 

the mines were to a mixture of chrysotile asbestos fibers and EMPs of related nonasbestiform 

minerals (i.e., antigorite and lizardite) [Wylie 

and Bailey 1992]. Stayner et al. [1997] also 

point out, in comparing a number of epidemiological studies, that the variation in relative 

risk for lung cancer is often greater within an 

industry (e.g., mining or textile) than between 

varieties of asbestos.

Some have argued that pure chrysotile may not 

be carcinogenic and that increased respiratory cancer among chrysotile workers can be explained by the presence of tremolite asbestos 

as a contaminant of chrysotile [McDonald and 

McDonald 1997]. This is referred to as the amphibole hypothesis. However, several studies of 

workers using chrysotile with very little contamination by tremolite have demonstrated strong 

relationships between exposure to chrysotile 

and lung cancer. A study of chrysotile asbestos 

workers in China [Yano et al. 2001] found an 

age- and smoking-adjusted relative risk of 8.1 

for lung cancer among highly exposed workers, compared to workers with low exposure to 

asbestos. The identified contamination of the 

chrysotile by tremolite was less than 0.001%. In 

the South Carolina textile mill study, a strong relationship between lung cancer and chrysotile 

exposure has been demonstrated [Dement et 

al. 1994; Hein et al. 2007]. The plant also processed less than 2000 lbs of crocidolite yarn per 

year from the early 1950s until 1972. This small 

amount of crocidolite was processed at one location, wet or lubricated with oil or graphite, 

to unite woven tape and braided packing [McDonald et al. 1983]. Since crocidolite was never 

carded, spun, or twisted, the predominant exposure at the plant was to chrysotile asbestos. A recent reanalysis by transmission electron microscopy (TEM) of archived fiber samples collected 

from the study facility in 1965 and 1968 identified only two amphibole fibers among 18,840 fiber structures (0.01%) in archived airborne dust 

samples from that textile mill study; the remainder were identified as chrysotile [Stayner et al. 

2007]. Additionally, in fiber burden studies of 

malignant mesothelioma in humans, chrysotile 

fibers were often present in mesothelioma tissue, 

even in the absence of detectable amphibole fibers [Suzuki and Yuen 2001], though this alone 

does not constitute conclusive evidence of a role 

for chrysotile in the etiology of mesothelioma. 

In addition to analyses of air samples from epidemiologic studies, UICC chrysotile B was analyzed, with special attention given to identifying tremolite contamination. Analysis of more 

than 20,000 fibers identified only particles with 

the characteristics of chrysotile, not tremolite 

[Frank et al. 1998]. Additionally, Kohyama et 

al. [1990] reported no amphibole asbestos was 

found in UICC chrysotile B at the detection level of 0.1%. This material has been used in an inhalation experiment that produced lung cancers 

and mesotheliomas [Wagner et al. 1974] and 

another study reporting mesotheliomas after 

intrapleural inoculation [Wagner et al. 1973].

A possible difference in risk for carcinogenicity 

between chrysotile and amphibole asbestos exposures has been investigated in animal model studies. In a one-year rat inhalation study, 

chrysotile samples were extremely fibrogenic 

and carcinogenic. Pulmonary carcinomas developed in approximately 25% of animals, 
36 NIOSH CIB 62 • Asbestos

and advanced interstitial fibrosis developed in 

lung tissue in 10% of all older animals, whereas intrapleural injection studies produced 

mesotheliomas in over 90% of animals [Davis et al. 1986]. It was noted that very little 

chrysotile remained in the lungs of the animals 

that survived longest following dust inhalation. From this it was suggested that chrysotile 

is very potent in rodents but, except where exposure levels are very high and of long duration, may be less hazardous to man because 

chrysotile fibers are removed from lung tissue more rapidly than are amphibole fibers. In 

a further analysis of the data, using regenerated dusts, Berman et al. [1995] found that although chrysotile and amphiboles do not differ 

in potency for lung tumor induction, mineralogy is a determinant of the relative potency of 

inhaled dusts for mesothelioma induction, and 

chrysotile is less potent than amphiboles.

Hodgson and Darnton [2000] reviewed the literature and estimated that, at exposure levels 

seen in occupational cohorts, the exposurespecific risk of mesothelioma from the three 

principal commercial asbestos types is broadly in the ratio 1:100:500 for chrysotile, amosite, 

and crocidolite, respectively, and the risk differential for lung cancer between chrysotile fibers 

and the two varieties of amphibole asbestos 

fibers is between 1:10 and 1:50. In 2009, Loomis et al. [2009] reported the results of a mortality study of chrysotile textile workers which 

found increased risks of both mesothelioma 

and lung cancer. The increase in mesothelioma 

and pleural cancer in this cohort was consistent with the average of 0.3% mesothelioma 

deaths in the cohorts that previously had been 

reported by Stayner et al. [1996] based on 

12 studies of workers exposed to chrysotile 

in mining and processing plants, but higher 

than the estimates reported by Hodgson and 

Darnton [2000]. Based on the findings of Loomis et al. [2009], Hodgson and Darnton [2010] 

reanalyzed their data. They found that cumulative risk of mesothelioma for chrysotile-exposed asbestos workers in processing plants 

was approximately an order of magnitude 

greater than the risk they had previously reported for mines and processing plants combined, and commented that this risk is still at 

least an order of magnitude lower than that associated with exposure to amphibole asbestos 

[Hodgson and Darnton 2010]. 

A recent analysis of potency factors of various minerals estimated that the relative potency of chrysotile for producing mesothelioma 

ranged between zero and 1/200th that of amphibole asbestos and that amphibole asbestos and chrysotile were not equally potent in 

producing lung cancer [Berman and Crump 

2008b]. However, the Asbestos Committee of 

EPA’s Science Advisory Board expressed substantial concern that the scientific basis for a 

similar modeling approach being considered 

by EPA for risk assessment was weak and inadequate, and specifically cited the lack of available data to estimate TEM-specific levels of exposure for epidemiological studies used in the 

analysis [EPA 2008a]. Subsequently, EPA chose 

not to pursue this approach [EPA 2008b].

2.8.2 Asbestiform Amphibole 

Minerals

Asbestiform amphibole fibers consist of aggregates of long, thin, flexible fibrils that separate along grain boundaries between the fibrils. Because the fibril diameter of crocidolite 

is less than that of anthophyllite asbestos but 

the flexibility is greater, there is an indication 

that flexibility is a function of fibril diameter. As with chrysotile, the dimensions of individual amphibole asbestos fibers depend on 
NIOSH CIB 62 • Asbestos 37

the extent to which the material has been manipulated. There are conflicting reports on the 

splitting of amphibole fibers in vivo. Following 

intrapleural inoculation in rats, ferroactinolite 

and amosite have been reported to split longitudinally in the lung, resulting in increased 

numbers of thinner fibers with increased aspect ratio [Coffin et al. 1982, 1992; Cook et al. 

1982], and crocidolite has also been observed 

to split longitudinally [Coffin et al. 1992]. In 

other studies, crocidolite splitting was not observed, even after several years [Bellman et al. 

1987]. Longitudinal splitting of fiber bundles 

after entering the lung represents one way that 

air sample counts may underestimate the cumulative dose of fibers in the lung.

There is little scientific debate that the asbestiform 

varieties of the five commercially important amphibole asbestos minerals are carcinogenic and 

should be covered by regulations to protect 

workers. However, concerns have been raised 

that the current OSHA and MSHA asbestos regulations and even the current NIOSH REL for 

airborne asbestos fibers, which explicitly cover 

the asbestiform varieties of the six commercially 

important asbestos minerals, should be expanded to provide worker protection from exposure 

to EMPs from asbestiform minerals.

This concern is exemplified by exposures to 

winchite and richterite fibers at a vermiculite 

mine near Libby, Montana, where exposures to 

the these fibers have resulted in high rates of 

lung fibrosis and cancer among exposed workers, similar to the occurrence of asbestos-related 

diseases among asbestos-exposed workers in 

other industries [Amandus and Wheeler 1987; 

Amandus et al. 1987a,b; McDonald et al. 2004; 

Sullivan 2007; Rohs et al. 2008]. Workers at the 

mine and residents of Libby were exposed to 

EMPs identified (on the basis of the 1997 IMA 

amphibole nomenclature) as the asbestiform 

amphiboles winchite and richterite, as well as 

tremolite asbestos [Meeker et al. 2003].

The recently updated NIOSH cohort study of 

Libby workers found elevated SMRs for asbestosis (SMR 165.8; 95% CI 103.9–251.1), lung 

cancer (SMR 1.7; 95% CI 1.4–2.1), cancer of 

the pleura (SMR 23.3; 95% CI 6.3–59.5), and 

mesothelioma [Sullivan 2007]. An exposureresponse relationship with duration of employment and total fiber-years cumulative exposure 

was demonstrated for both asbestosis and lung 

cancer. Significant excess mortality from nonmalignant respiratory disease was observed 

even among workers with cumulative exposure <4.5 fibers/cc-years (i.e., a worker’s cumulative lifetime exposure, if exposed to asbestos 

fibers at the current OSHA standard of 0.1 f/cm3

over a 45-year working life). IARC stated mineral substances (e.g., vermiculite) that contain 

asbestos should also be regarded as “carcinogenic to humans” (Group 1) [IARC 2009]. Vermiculite from the Libby mine was used to produce loose-fill attic insulation, which remains in 

millions of homes around the United States, and 

homeowners and/or construction renovation 

workers (e.g., plumbers, cable installers, electricians, telephone repair personnel, and insulators) are potentially exposed when this loosefill attic insulation is disturbed.

Because winchite and richterite are not explicitly listed among the six commercial asbestos 

minerals, it is sometimes assumed that they 

are not included in the regulatory definition 

for asbestos. However, some of what is now referred to as asbestiform winchite and richterite 

in the 1997 IMA nomenclature would have 

been accurately referred to as tremolite asbestos according to the analytical criteria (optical methods of identification) specified in the 

1978 IMA nomenclature [Meeker et al. 2003]. 

Furthermore, an even greater portion of this 
38 NIOSH CIB 62 • Asbestos

richterite and winchite would have been identified as tremolite asbestos according to the 

optical methods of identification used prior to 

1978. In fact, over the years, amphibole minerals from the Libby mine that are now referred 

to as winchite and richterite were identified by 

mineralogists using then-current terminology as soda tremolite [Larsen 1942], soda-rich 

tremolite [Boettcher 1966], and tremolite asbestos and richterite asbestos [Langer et al. 

1991; Nolan et al. 1991]; NIOSH identified exposures to workers as tremolite in reports of 

the Libby mine epidemiological studies in the 

1980s [Amandus and Wheeler 1987; Amandus 

et al. 1987a,b].

Similar to the situation in Libby, a study of a 

cluster of malignant mesothelioma cases in eastern Sicily has implicated an etiological role for 

an asbestiform amphibole in the fluoro-edenite 

series, initially identified as a mineral in the 

tremolite-actinolite series [Comba et al. 2003].

In the face of past and future nomenclature 

changes in the mineralogical sciences, workers need to be protected against exposures to 

pathogenic asbestiform minerals. The health 

and regulatory communities will need to carefully define the minerals covered by their policies and monitor the nomenclature changes to minimize the impact of these changes on 

worker protections.

2.8.3 Other Minerals of 

Potential Concern 

By analogy to asbestiform amphiboles, there 

is reason to be concerned about potential for 

health risks associated with inhalational exposure to EMPs not covered by asbestos policies.

Erionite is perhaps the most worrisome known 

example [HHS 2005b]. An epidemic of malignant 

mesothelioma affecting several villages in Central Turkey has been studied for several decades 

[Baris et al. 1981]. Homes and other buildings in 

those villages were traditionally constructed of 

blocks of local volcanic stone containing erionite, 

a fibrous zeolite mineral. A recently published 

prospective mortality study has documented that mesothelioma accounts for over 40% of 

deaths among those residing in the affected villages [Baris and Grandjean 2006]. This localized 

epidemic of malignant mesothelioma produced 

an opportunity for a pedigree study that found 

a strong genetic influence on erionite-caused 

mesothelioma [Dogan et al. 2006]. As with exposure to asbestos, there is evidence that exposure to erionite causes other malignant tumors 

[Baris et al. 1996] and pleural plaques [Karakoca 

et al. 1997] in addition to mesothelioma. Likewise, as with amphiboles, the mineralogy of zeolites, including erionite, appears to be complicated and subject to misclassification [Dogan 

and Dogan 2008]. Although no clear epidemic 

of erionite-caused disease has been documented 

elsewhere, the mineral occurs in the intermountain west of the United States and a recent publication purports to be the first to report a case of 

erionite-associated malignant mesothelioma in 

North America [Kliment et al. 2009]. 

The International Agency for Research on Cancer (IARC) has considered evidence relevant to 

carcinogenicity for several EMPs [IARC 1977, 

1987a, 1997]. In addition to the traditional 

commercial asbestos, IARC has made assessments that the evidence is sufficient to determine that both erionite and talc containing 

asbestiform fibers are human carcinogens (i.e., 

Group 1) [IARC 2009]; the evidence for carcinogenicity of nonasbestiform talc was judged 

to be insufficient to determine human carcinogenicity (i.e., Group 3) [IARC 1987a]. A Group 

3 determination means that “the available 

studies are of insufficient quality, consistency 
NIOSH CIB 62 • Asbestos 39

or statistical power to permit a conclusion regarding the presence or absence of a causal association, or no data on cancer in humans are 

available” [IARC 1997]. On the basis of studies 

in rats, palygorskite (attapulgite) fibers longer 

than 5 mm were determined to be possibly carcinogenic to humans (Group 2B) [IARC 1997]. 

In experimental animals the evidence was limited for the carcinogenicity of long sepiolite fibers 

(>5  μm) and inadequate to assess carcinogenicity of nonerionite fibrous zeolites (including clinoptilolite, mordenite, and phillipsite) 

and wollastonite (Group 3) [IARC 1997]. These 

Group 3 determinations highlight the need for 

additional research on nonasbestiform EMPs.

2.9 Determinants of Particle 

Toxicity and Health Effects

Current recommendations for assessing occupational and environmental exposures to asbestos fibers rely primarily on dimensional 

and mineralogical characteristics. Dimension, 

which influences the deposition of EMPs in the 

lung, lung clearance mechanisms, and retention 

time in the lung, is an important determinant 

of toxicity. However, other particle characteristics, such as durability in lung fluids, chemical composition, and surface activity, may also 

play important roles in causing respiratory diseases. Research to elucidate what roles these 

EMP characteristics play in causing biological responses may help to provide better evidence-based recommendations for asbestos fibers and other EMPs.

2.9.1 Deposition

Deposition of airborne particles in the respiratory system is defined as the loss of particles from the inspired air during respiration. 

Clearance pertains to the removal of deposited 

particles by diverse processes over time, whereas retention is the temporal persistence of particles within the respiratory system [Morrow 1985]. 

The deposition of inhaled particles in the respiratory tract is a function of their physical characteristics (dimension and density), the anatomical 

and physiological parameters of the airways, and 

the rate and depth of respiration [Yu et al. 1986]. 

Although particle chemical composition does 

not play a role in deposition, respiratory clearance 

of all particle types is dependent on both physical and chemical characteristics of the particle. 

In addition, surface charge and hydrophilicity, as 

well as adsorbed materials (e.g., coatings on synthetic fibers) and other physical and chemical factors, determine whether small particles and fibers 

will agglomerate into larger, nonrespirable masses [ILSI 2005].

Depending on their physical characteristics, inhaled particles are differentially deposited in one 

of the following three respiratory system compartments: the extrathoracic region, consisting 

of the anterior and posterior nose, mouth, pharynx, and larynx; the bronchial region, consisting 

of the trachea, bronchi, and bronchioles down 

to and including the terminal bronchioles; and 

the alveolar-interstitial region, consisting of the 

respiratory bronchioles, alveolar ducts, and alveolar sacs.

Important parameters for the deposition of 

airborne particles are their aerodynamic and 

thermodynamic properties. Below a particle 

size of 0.5 μm aerodynamic equivalent diameter (AED), thermodynamic properties prevail. The AED of EPs is mostly determined by 

their geometric diameter and density. Deposition of EPs in an airway is strongly related to 

the orientation of the particles with respect 

to the direction of the air flow and is affected 

by the interrelationship of four major deposition mechanisms: impaction, interception, 
40 NIOSH CIB 62 • Asbestos

sedimentation, and diffusion [Asgharian and 

Yu 1988]. In a study to assess EP deposition in 

the tracheobronchial region, Zhou et al. [2007] 

evaluated the deposition efficiencies of carbon 

fibers (3.66  μm diameter), using two human 

airway replicas that consisted of the oral cavity, 

pharynx, larynx, trachea, and three to four generations of bronchi. Carbon fiber deposition 

was found to increase with the Stokes number, 

indicating that inertial impaction is the dominant mechanism. Also, fiber deposition in the 

tracheobronchial region was lower than that of 

spherical particles at a given Stokes number, 

indicating a greater likelihood for small-width 

EPs to move past the upper respiratory tract 

and reach the lower airways where diffusional deposition predominates [Yu et al.1986]. 

These results were confirmed by results of later studies evaluating the deposition of asbestos, using a similar tracheobronchial cast model [Sussman et al. 1991a, b]. The probability of 

deposition of a particle in a specific location in 

the airways is not the same as the probability 

of penetration to that region, and for particles 

in a certain range of AEDs, the difference between penetration and deposition may be substantial [ICRP 1994].

2.9.2 Clearance and Retention 

A variety of mechanisms are associated with the 

removal of deposited particles from the respiratory tract [Warheit 1989]. Physical clearance 

of insoluble particles deposited in the lung is 

an important physiological defense mechanism 

that usually serves to moderate any risk that 

might otherwise be associated with exposure to 

particles. Inhaled particles that deposit on respiratory tract surfaces may be physically cleared 

by the tracheobronchial mucociliary escalator or nasal mucus flow to the throat, and then 

they may be either expectorated or swallowed. 

Clearance depends upon the physicochemical 

properties of the inhaled particles, the sites of 

deposition, and respiratory anatomy and physiology. For example, inhaled insoluble particles with larger AEDs tend to deposit on the 

nasopharyngeal mucus and are generally cleared 

by sneezing or nose blowing or by flow into the 

oropharynx, where they are swallowed. Insoluble particles with smaller AEDs tend to deposit lower in the respiratory tract, with associated 

longer retention times. Those deposited in the 

alveolar region are subject to longer retention 

times than those deposited on the bronchial region [Lippmann and Esch 1988].

The most important process for removal of insoluble particles from the airways is mucociliary 

clearance, which involves a layer of mucus propelled by the action of ciliated airway cells 

that line the trachea, bronchi, and terminal 

bronchioles [Warheit 1989]. The mucociliary 

transport system is sensitive to a variety of 

agents, including cigarette smoke and ozone 

[Vastag et al. 1985]. These toxicants affect the 

speed of mucus flow and consequent particle 

clearance by altering ciliary action and/or modifying the properties and/or amount of mucus. 

Chronic exposure to cigarette smoke has been 

shown to cause a prolonged impairment of particulate clearance from the bronchial region. 

This impaired clearance is associated with increased retention of asbestos fibers in the bronchi, where they stimulate inflammatory processes in the bronchial epithelium [Churg and 

Stevens 1995; Churg et al. 1992].

Because the alveolar region of the lung does 

not possess mucociliary clearance capability, particles (generally <2  μm AED) deposited in this region are cleared at a much slower 

rate than particles deposited in the bronchial region. Particles that are soluble may dissolve and be absorbed into the pulmonary 
NIOSH CIB 62 • Asbestos 41

capillaries, whereas insoluble particles may 

physically translocate from the alveolar airspace [Lippmann et al. 1980; Lippmann and 

Schlesinger 1984; Schlesinger 1985]. Most insoluble EPs that deposit in the alveolar regions 

are phagocytized (i.e., engulfed) by alveolar 

macrophages. Macrophages contain lysosomes 

packed with digestive enzymes, such as acid 

hydrolases, at acidic pH levels. Lysosomal contents are capable of digesting many—though not 

all—types of phagocytized particles. Alveolar 

macrophages that have phagocytized particles 

tend to migrate to the bronchoalveolar junctions, where they enter onto the mucociliary 

escalator for subsequent removal from the 

lung [Green 1973]. It has been postulated by 

some investigators that dissolution of particles within macrophages is a more important 

determinant of long-term clearance kinetics 

for many mineral dusts than is mucociliary 

transport and the migratory potential of lung 

macrophages [Brain et al. 1994]. However, 

certain circumstances can disrupt the normal 

phagosomal function of alveolar macrophages. 

One such circumstance involves the toxic 

death of macrophages initiated by highly reactive particle surfaces (e.g., crystalline silica 

particles). Another such circumstance involves 

overwhelming the capacity of macrophages 

by an extreme burden of deposited particles, 

sometimes referred to as “overload,” even by 

particles that would be considered “inert” at 

lower doses. A third type of circumstance, typified by asbestos fibers, involves EPs that, even 

though having a small enough AED (defined 

primarily by particle width) to permit deposition in the alveolar region, cannot be readily phagocytized because particle length exceeds macrophage capacity. When alveolar 

macrophages attempt to phagocytize such EPs, 

they cannot completely engulf them (sometimes referred to as “frustrated phagocytosis”), 

and lysosomal contents are released into the alveolar space. Frustrated phagocytosis can initiate a process in which reactive oxygen species 

(ROS) are generated, stimulating the induction 

of tumor necrosis factor-alpha (TNF-α). TNF-α 

is considered an inflammatory and fibrogenic 

cytokine that plays an important role in the pathogenesis of pulmonary fibrosis [Blake et al. 1998].

All three types of disruption of normal macrophage function contribute to decreased particle clearance rates and can result in inflammation of the alveolar spaces. In addition, 

particles that are not phagocytized in the alveoli can translocate to the lung interstitium, 

where they may be phagocytized by interstitial macrophages or transported through the 

lymphatic system to pulmonary lymph nodes 

[Lippmann et al. 1980; Lippmann and Schlesinger 

1984; Schlesinger 1985; Oberdorster et al. 1988]. 

Tran and Buchanan [2000] have reported findings suggesting that sequestration of particles 

in the interstitial compartment is more prominent in exposed humans than is the observed 

retention of particles due to overload in animal 

studies. The importance of interstitialization in 

humans is consistent with the kinetic differences observed in lung clearance rates in humans and rats. The first-order rate coefficient 

for alveolar clearance is approximately 1 order of magnitude faster in rats than in humans 

[Snipes 1996], which may allow for greater 

interstitialization of particles in humans at all 

levels of lung dust burden. These findings indicate that adjustment of kinetic differences 

in particle clearance and retention is required 

when using rodent data to predict lung disease 

risks in humans and that current human lung 

models underestimate working lifetime lung 

dust burdens in certain occupational populations [Kuempel et al. 2001].
42 NIOSH CIB 62 • Asbestos

Evidence from in vivo studies in rodents and in 

vitro studies indicates that EPs (vitreous glass 

and EMPs) with a length equal to or greater 

than the diameter of rodent lung macrophages 

(about 15 μm) are most closely linked to biological effects observed in rodent lungs [Blake 

et al. 1998]. Alveolar macrophages appear to 

be capable of phagocytizing and removing EPs 

shorter than approximately 15  μm, either by 

transport to the mucociliary system or to local 

lymph channels. With increasing length above 

approximately 15 μm, alveolar macrophages appear to be increasingly ineffective at physical removal, resulting in differential removal rates for 

EPs of different lengths. Although EP lengths 

greater than 15 μm appear to be associated with 

toxicity in experimental studies with rodents, a 

“critical” length for toxicity in humans is probably greater than 15  μm [Zeidler-Erdely et al. 

2006]. For long EPs that cannot be easily cleared 

by macrophages, biopersistence in the lung is 

influenced by the ease with which the EPs break 

into shorter lengths.

2.9.3 Biopersistence and Other 

Potentially Important Particle 

Characteristics

It has been hypothesized that the differences in crystalline structure between amphibole 

asbestos fibers and amphibole cleavage fragments account for apparent differences in toxicological response to these particles. Cleavage 

fragments that meet the dimensional criteria for countable particles under federal regulatory policies for asbestos fibers are generally shorter and wider than asbestos fibers 

[Siegrist and Wylie 1980; Wylie 1988]. This 

dimensional difference between populations 

of asbestos fibers and populations of cleavage fragments might contribute to generally 

shorter biopersistence in the lung for cleavage 

fragments than for asbestos fibers. Asbestos fibers also tend to separate longitudinally once 

deposited in the lung, thus increasing the total 

number of retained fibers without an accompanying reduction in lengths of the retained 

fibers [NRC 1984]. In contrast, cleavage fragments tend to break transversely because of 

dissolution of their weaker crystalline structure, resulting in shorter particles that can be 

more easily cleared through phagocytosis and 

mucociliary clearance [Zoltai 1981]. The impact of these structural differences on solubility in lung fluids warrants study, because substantial differences in solubility in lung fluids 

between asbestos fibers and other EMPs (including amphibole cleavage fragments) could 

translate into differences in toxicity.

2.9.3.1 Biopersistence

Dissolution of EPs in the lung is a poorly understood process that is dependent on particle 

characteristics, biological processes, and concomitant exposure to other particulates. The 

ability of an EP to be retained and remain intact 

in the lung is considered an important factor in 

the process of an adverse biological response. 

EPs of sufficient length that remain intact and 

are retained in the lung are thought to pose the 

greatest risk for respiratory disease. The ability 

of an EP to reside long-term in the lung is generally referred to as biopersistence. Biopersistence 

of EPs in the lung is a function of site and rate 

of deposition, rates of clearance by alveolar 

macrophages and mucociliary transport, solubility in lung fluids, breakage rate and breakage 

pattern (longitudinal or transverse), and rates 

of translocation across biological membranes. 

The rates of some of these processes can affect 

the rates of other processes. For example, a high 

rate of deposition in the alveolar region could 

potentially overwhelm macrophage clearance 
NIOSH CIB 62 • Asbestos 43

mechanisms and increase the rate of translocation to the lung interstitium.

The persistence of an EP in the lung is influenced 

by changes that may occur in its dimension, surface area, chemical composition, and surface 

chemistry. Differences in any of these characteristics can potentially result in differences in 

clearance and retention and affect toxic potential. For example, EPs too long to be effectively 

phagocytized by alveolar macrophages will tend 

to remain in the alveolar compartment and be 

subjected to other clearance mechanisms, including dissolution, breakage, and translocation 

to interstitial sites and subsequently to pleural 

and other sites.

The durability of EPs residing in the lung is an 

important characteristic influencing biopersistence. An EP’s durability is generally measured 

by its ability to resist dissolution and mechanical disintegration after being subjected to lung 

extracellular fluid (approximate pH of 7) and 

lysosomal fluids (approximate pH of 5). EPs 

that are more soluble will be less biopersistent, 

and thicker EPs may take longer to dissolve 

than thinner EPs, all else being equal. For example, long, thin EPs that are not very durable could dissolve and/or fragment into shorter EPs, increasing their probability of being 

cleared from the lung and thus potentially decreasing lung retention time and risk for fibrotic or neoplastic effects. Some EPs, such as certain types of glass fibers, are fairly soluble in 

lung fluid and are cleared from the lung in a 

matter of days or months. Other EPs, such as 

amphibole asbestos, can remain in the lung for 

decades. It has been suggested that some types 

of EPs may alter the mobility of macrophages 

and the translocation of EPs to the pleura or 

lymph nodes [Davis 1994]. No relationship has 

been established between biopersistence of EPs 

in the lung and the risk of induction of genetic 

and epigenetic changes that may lead to cancer [Barrett 1994]. Although some evidence 

indicates that durability may be a determinant 

of toxicity for various synthetic vitreous fibers 

(SVFs), EMPs need to be evaluated to determine whether they conform to this paradigm 

[ILSI 2005].

Measurement of the biopersistence of various 

EMPs has been suggested as a means for estimating their relative potential hazard. Short-term 

inhalation and intratracheal instillation studies 

have been used to determine the biopersistence 

of various SVFs and asbestos fibers. Animal inhalation studies are preferred over animal tracheal instillation studies to assess biopersistence 

because they more closely mimic typical human exposure. The European Commission has 

adopted specific testing criteria that permit the 

results from either short-term biopersistence 

studies or chronic animal studies to be used as a 

basis for determining carcinogenicity [European Commission 1997]. 

Several animal inhalation studies have indicated that oncogenic potential of long SVFs can 

be determined by their biopersistence [Mast 

et al. 2000; Bernstein et al. 2001; Moolgavkar 

et al. 2001]. It has been suggested that a certain minimum persistence of long EPs is necessary before even minute changes appear in 

the lungs of exposed animals [Bernstein et al. 

2001]. Furthermore, Moolgavkar et al. [2001] 

have suggested that EP-induced cancer risk, 

in addition to being a linear function of exposure concentration, is also a linear function of 

the weighted half-life of EPs observed in inhalation studies with rats. Also, dosimetry models for rodents and humans indicate that, on a 

normalized basis, EP clearance rates are lower 

in humans than in rats [Maxim and McConnell 

2001] and that EPs frequently sequester in the 

interstitial compartment of humans [Snipes 
44 NIOSH CIB 62 • Asbestos

1996; Tran and Buchanan 2000]. Thus, results 

from chronic inhalation studies with rodents 

exposed to EPs may underestimate risks for 

humans, and adjustment for kinetic differences 

in particle clearance and retention in rats is required to predict lung disease risks in humans 

[Kuempel et al. 2001]. 

Studies using in vitro assays have been conducted with various SVFs and silicate minerals 

to determine the dissolution rate in simulated 

lung and lysosomal fluids [Hume and Rimstidt 

1992; Werner et al. 1995; Hesterberg and Hart 

2000; Jurinski and Rimstidt 2001]. In vitro dissolution studies can provide a rapid and more 

controlled alternative to classic long-term toxicity testing in animals and could provide useful information when performed as companion 

experiments with in vivo studies if conditions 

of exposure and test agent can be made similar. The design of in vitro assays is intended to 

mimic the biological conditions that exist in the 

lung once the EP comes into contact with lung 

tissue or macrophages. Although uncertainties 

exist about the specific physiological processes 

that occur in the lung, results from in vitro assays can provide some insight into the chemical reactions that influence EP dissolution. For 

example, it appears that EP (e.g., glass fiber) 

dissolution occurs more readily when the EP 

is in contact with a fluid that is undersaturated 

with respect to the EP’s composition. The condition of undersaturation must be maintained 

at the EP’s surface for dissolution to continue. 

If an EP is surrounded by a saturated or supersaturated solution (compared to the EP composition), then no further dissolution occurs.

The results from many in vitro experiments 

demonstrate different patterns of dissolution 

for most of the tested EP types (i.e., glass, asbestos) under various test conditions. This effect 

was most notable in those experiments where 

different pH conditions were used. Fluid pH 

appears to influence the creation of complexes 

from the leached elements of the EP, which in 

turn alters the rate of solubility. Chrysotile fibers 

tend to dissolve readily in acids because of the 

preferential leaching of magnesium (Mg) from 

the fiber. The leaching of Mg from tremolite and 

anthophyllite and of sodium from crocidolite 

also occurs more readily in acid conditions. 

The rate of EP dissolution has also been observed to be affected by differing internal and 

surface structures. EPs with porous or rough 

surfaces have larger surface areas than smooth 

EPs with the same gross dimensions. These 

larger surface areas interact more readily with 

the surrounding medium because of the greater number of sites where solute molecules can 

be absorbed. EMPs with cleavage plane surfaces will contain varying degrees of defects; 

the higher the number of surface defects, the 

greater the potential instability of the particle. 

Dissolution of these types of EMPs is typically initiated where surface vacancies or impurities are present [Searl 1994]. Chrysotile asbestos is an example of a sheet silicate made up 

of numerous fibrils composed of tightly bound 

rolled layers of Mg hydroxide. These Mg hydroxide layers are readily leached by acid solutions within human tissues [Spurny 1983], 

causing disintegration of the fibril’s crystalline structure. In contrast, the amphibole asbestos minerals are chain silicates with a crystalline structure comprising alkali and alkali 

earth metals that are tightly bound, making 

the fibers less susceptible to dissolution. In 

contrast to the crystalline structure of the asbestos fibers, some high-temperature glass fibers are more stable than chrysotile fibers because they are composed of silicate chains, 

sheets, and frameworks [Searl 1994]. The absence of cleavage planes or structural defects 

in glass fibers limits the degree to which fluids 
NIOSH CIB 62 • Asbestos 45

can penetrate their interior to promote dissolution. Chrysotile fibers were found to be less 

durable in rat lungs than some high-temperature SVFs [Bellmann et al. 1987; Muhle et al. 

1987] but more durable in physiological solutions than some refractory ceramic fibers 

(RCFs) [Scholze and Conradt 1987].

EP surface characteristics (e.g., structural defects, porosity) and composition affect not 

only the rate of dissolution but also the manner 

in which dissolution occurs. In some instances, surface dissolution will cause alterations in 

internal structure sufficient to cause mechanical breakage. In some studies, slagwools and 

rockwools exposed to water developed irregular surfaces, creating stress fractures that 

caused transverse breakage [Bellmann et al. 

1987]. Similar occurrences of glass fiber breakage have been observed when there was leaching of alkaline elements [Searl 1994].

Results from in vitro and short-term in vivo

studies conducted with various EMPs and 

SVFs provide some confirmation that persistence of EPs in the lung is influenced by particle durability [Bernstein et al. 1996]. However, 

other evidence suggests that, because of the relatively short biodurability of chrysotile fibers, any 

damage to the lung tissue caused by chrysotile fibers must be initiated soon after exposure [Hume 

and Rimstidt 1992], suggesting that biopersistence 

of EPs in the lung may be only one of many factors 

that contribute to biological response. A better understanding of the factors that determine the biological fate of EMPs deposited in the lung is critical to understanding the mechanisms underlying 

differences in toxic potential of various EMPs of 

different dimensions and compositions. Because 

biopersistence of EMPs is thought to play an important role in the development of disease, it may 

eventually prove to be an important characteristic 

to incorporate into occupational safety and health 

policies concerning exposures to EMPs.

2.9.3.2 Other Potentially Important 

Particle Characteristics

Surface composition and surface-associated activities have been suggested as factors affecting the potential for disease induction by EMPs 

(e.g., asbestos) [Bonneau et al. 1986; Kane 1991; 

Jaurand 1991; Fubini 1993]. For nonelongate respirable mineral particles (e.g., crystalline silica), 

surface composition and surface interactions can 

directly and profoundly affect in vitro toxicities 

and in vivo pathogenicity; they can also directly cause membranolytic, cytotoxic, mutagenic, or 

clastogenic damage to cells and have been shown 

to induce fibrogenic activities in animals and humans. Investigation is warranted to confirm that 

these effects of surface composition and surface 

interactions also apply to EMPs. One strategy 

is to determine the effects of well-characterized 

surface modification of different types of EMPs 

on cell-free interactions with biological materials, 

in vitro cellular cytotoxicities or genotoxicities, 

and pathology in animal models.

Surface properties of mineral fibers and other EMPs may have direct impact on cytotoxic 

or genotoxic mechanisms responsible for 

fibrogenic or carcinogenic activity. Chemical 

surface modification of asbestos fibers has been 

shown to affect their cytotoxicity [Light and 

Wei 1977a,b; Jaurand et al. 1983; Vallyathan 

et al. 1985]. Although asbestos fibers clearly 

can be carcinogenic, they are not consistently 

positive in genotoxicity assays; their principal 

damage is chromosomal rather than gene mutation or DNA damage [Jaurand 1991]. One 

study linked cytotoxicity with in vitro mammalian cell transformation [Hesterberg and 

Barrett 1984]; thus, surface factors affecting 

cytotoxicity might affect potential for inducing 
46 NIOSH CIB 62 • Asbestos

some genotoxic activities. However, modifying the surface of a well-characterized sample of chrysotile fibers by depleting surface Mg 

while retaining fiber length did not result in a 

significant quantitative difference for in vitro

micronucleus induction between the native 

and surface-modified materials, both of which 

were positive in the assay [Keane et al. 1999].

The surface of mineral fibers and other EMPs 

also might be an indirect but critical factor in 

the manifestation of pathogenic activity. EMP 

surfaces may be principal determinants of EMP 

durability under conditions of in vivo dissolution in biological fluids. As such, they would 

be a controlling factor in biopersistence, critical to the suggested mechanisms of continuing 

irritation or inflammatory response in causing 

fibrosis or neoplastic transformation.

2.9.4 Animal and In Vitro

Toxicity Studies

Over the last half-century, in vivo animal 

model studies have explored induction of lung 

cancer, mesothelioma, and pulmonary fibrosis 

by asbestos fibers and other EMPs following 

intrapleural, intraperitoneal, or inhalation challenge. Numerous cell-free, in vitro cellular, and 

in vivo short-term animal model studies have 

been pursued, attempting to (1) examine tissue 

and cellular responses to EMPs and impact of 

EMP conditioning on these responses; (2) identify and evaluate interactions and mechanisms 

involved in pathogenesis; and (3) seek morphological or physicochemical EMP properties controlling those mechanisms. These short-term 

studies provide an evolving basis for design or 

interpretation of higher-tier chronic exposure 

studies of selected EMPs.

Some of the short-term studies have addressed 

the following: 

• the general question of extrapolating human health effects from in vivo animal 

model studies; 

• the physiological relevance of in vitro cellular studies of EMP toxicities;

• the association of EMP dimensions with 

pathology demonstrated in animal model studies;

• the potential mechanisms and associated 

EMP properties responsible for initiating 

cell damage;

• the extensive information now available on a 

“central dogma” of subsequent intracellular 

biochemical pathway stimulation leading to 

toxicity or intercellular signaling in disease 

promotion; and

• the use of these mechanistic paradigms to 

explain specific questions of 

ȣ differences between the activities of asbestiform and nonasbestiform EMPs, 

including seemingly anomalous differences between some in vitro and in vivo

EMP activities;

ȣ differences between the activities of 

erionite fibers and amphibole asbestos fibers; and 

ȣ the possibility of EMP-viral co-carcinogenesis.

Several reviews and recommendations for animal model and cellular studies on these issues 

have been developed by expert workshops and 

committees. Early studies on the carcinogenicity of asbestos and erionite fibers were reviewed by IARC [1977, 1987a,b], and SVFs 

were reviewed more recently [IARC 2002]. 

Short-term in vivo and in vitro studies to elucidate mechanisms of fiber-induced genotoxicity 

and genetic mechanisms affecting fiber-induced 

lung fibrosis have been extensively reviewed. 
NIOSH CIB 62 • Asbestos 47

A review for the EPA by an international working group assembled in 2003 provides an update on short-term assay systems for fiber toxicity and carcinogenic potential [ILSI 2005], 

and two additional reviews discuss the fiber 

genotoxicity literature up to the current decade 

[Jaurand 1997; Schins 2002].

2.9.4.1 Model Systems Used to Study 

EMP Toxicity

The paucity of information on human health 

effects of some new synthetic EPs has led to renewed considerations of the value and limitations of animal model studies, as well as the interpretability of intrapleural, intraperitoneal, or 

inhalation challenge methods of animal model tests to make predictions of human health 

effects [IARC 2002]. One analysis concluded that rat inhalation is not sufficiently sensitive for prediction of human carcinogenicity by EMPs other than asbestos fibers [Muhle 

and Pott 2000]. Another review concluded that 

there are significant interspecies differences between the mouse, hamster, rat, and human, with the available evidence suggesting 

that the rat is preferable as a model for the human, noting that rats develop fibrosis at comparable lung burdens, in fibers per gram of dry 

lung, to those that are associated with fibrosis in humans. The review suggested that, on a 

weight-of-evidence basis, there is no reason to 

conclude that humans are more sensitive to fibers than rats with respect to the development 

of lung cancer [Maxim and McConnell 2001]. 

However, others suggest that, because inhaled 

particles frequently sequester in the interstitial 

compartment of humans, alveolar clearance is 

approximately one order of magnitude slower in humans than in rats [Snipes 1996; Tran 

and Buchanan 2000]. Those comparisons imply that results of inhalation studies with rats 

exposed to particles underestimate the risk for 

humans and that adjustment for kinetic differences in particle clearance and retention in rats 

is required to predict lung disease risks in humans [Kuempel et al. 2001].

How the results of in vitro tests that use cells or 

organ cultures apply to humans has been questioned because of differences in cell types and 

species-specific responses. It is difficult to isolate and maintain epithelial or mesothelial cells 

for use as models. Interpretation of in vitro test 

results may be limited because in vitro models 

may not consider all processes, such as clearance or surface conditioning, which occur in 

vivo. A major deficiency of in vitro systems is 

that biopersistence is not easily addressed. In 

addition to the usual exposure metric of mass, 

experimental designs should also include exposure metrics of EMP number and surface 

area [Mossman 2008; Wylie et al. 1997].

As frequently performed, in vitro assays of mineral particle-induced damage, measured by cell 

death or cytosolic or lysosomal enzyme release, 

do not adequately model or predict the results 

of in vivo challenge or epidemiological findings. 

For example, respirable aluminosilicate clay 

dust is as cytotoxic as quartz dust in such in vitro

assays, whereas quartz, but not clay, is strongly 

fibrogenic in vivo [Vallyathan et al. 1988].

2.9.4.2 Studies on Effects of 

Fiber Dimension

Early animal inhalation studies showed that 

chrysotile fibers induced fibrosis, hyperplasia 

of lung epithelial cells, and carcinomas in mice 

[Nordman and Sorge 1941] and tumors in rats 

[Gross et al. 1967]. Another study revealed 

lung carcinomas and mesotheliomas in rats after inhalation exposure to asbestos fiber samples of amosite, anthophyllite, crocidolite, and 

chrysotile [Wagner et al. 1974]. The effects of 
48 NIOSH CIB 62 • Asbestos

fiber length, width, and aspect ratio on carcinogenicity were addressed in a seminal study 

using a pleural surface implantation method of challenge in the rat [Stanton et al. 1977, 

1981]. Tests were performed on 72 durable 

EPs: 13 crocidolites; 22 glasses; 8 aluminum oxide sapphire whiskers; 7 talcs; 7 dawsonites; 4 

wollastonites; 2 asbestos tremolites; 1 amosite; 

2 attapulgites; 2 halloysites; 1 silicon carbide 

whisker; and 3 titanates. The incidence of malignant mesenchymal neoplasms a year after 

implantation correlated best with EPs that were 

longer than 8 μm and no wider than 0.25 μm, 

with relatively high correlations with EPs longer than 4 μm and no wider than 1.5 μm. This 

suggested that carcinogenicity of durable EPs 

depends on dimension and durability, rather 

than physicochemical properties. This is sometimes referred to as the Stanton hypothesis and 

has been the subject of continuing research. 

Reanalysis of the dimensions of seven of the 

crocidolite samples used in the 1981 study 

found that tumor probability was significantly correlated with the number of index particles (defined as particles longer than 8 μm and 

no wider than 0.25 μm), but the coefficient was 

low enough to suggest that factors other than 

size and shape play a role in carcinogenic effects of durable EPs [Wylie et al. 1987]. Further 

analysis confirmed the number of such index 

particles as the primary dimensional predictor 

of tumor incidence, but the correlation was increased when the data were analyzed by separate mineral types [Oehlert 1991]. These analyses suggested that mineral type is important, 

which is counter to the Stanton hypothesis.

Lippmann [1988] reviewed data from animal 

models exposed by instillation or inhalation of 

EMPs of defined size distributions, along with 

data on human lung fiber burden and associated effects, and concluded that (1) asbestosis 

is most closely associated with the surface area 

of retained EMPs; (2)  mesothelioma is most 

closely associated with numbers of EMPs longer than about 5  μm and thinner than about 

0.1 μm; and (3) lung cancer is most closely associated with EMPs longer than about 10 μm 

and thicker than about 0.15  μm. Lippmann 

[1988] also stated that the risk of lung cancer is 

associated with a substantial number of fibers 

longer than 10 μm with widths between 0.3 μm 

and 0.8  μm. A more recent review of the response to asbestos fibers of various lengths in 

animal models, along with data from studies of 

human materials, concluded that asbestos fibers of all lengths induce pathological responses; it suggested caution when attempting to exclude any subpopulation of inhaled asbestos 

fibers, on the basis of length, from being considered contributors to the development of asbestos-related diseases [Dodson et al. 2003].

2.9.4.3 Initiation of Toxic Interactions

A first question in seeking a full understanding 

of EMP properties and mechanisms responsible for fibrosis, lung cancer, or mesothelioma 

risks is the identity of initiating toxic interactions and the morphological, physical, and/or 

chemical properties of EMPs controlling them. 

Among proposed initiating mechanisms are 

these: (1) EMP surfaces generate ROS (even in 

vitro in the absence of cells), which are the primary toxicants to cells; (2)  EMP surfaces are 

directly membranolytic or otherwise directly cytotoxic or genotoxic to components of the 

cell, as are some nonelongate mineral particles, 

and that damage can cause necrosis, apoptosis, 

mutation, or transformation directly or by responsive cellular production of secondary reactive intermediates; and (3) EMP morphology itself can result in frustrated phagocytosis 

with an anomalous stimulation or release of 

ROS or other toxic reactive species.
NIOSH CIB 62 • Asbestos 49

2.9.4.3.1 Reactive Oxygen Species

Asbestos fibers can generate ROS or reactive 

nitrogen species in in vitro systems through 

direct aqueous-phase surface chemical reactions, as well as by stimulating secondary release of reactive species from cells. Electron 

spin resonance with use of spin-trapping techniques showed that crocidolite, chrysotile, and 

amosite asbestos fibers were all able to catalyze 

the generation of toxic hydroxyl radicals in a 

cell-free system containing hydrogen peroxide, 

a normal byproduct of tissue metabolism, and 

that the iron chelator desferroxamine inhibited 

the reaction, indicating a major role for iron in 

the catalytic process [Weitzman and Graceffa 

1984]. ROS generated by some EMP surfaces 

in cell-free media may provide toxicants to initiate cell structural or functional damage, including chromosomal or DNA genetic damage 

or aneuploidy from spindle apparatus damage. 

They also may activate cellular signaling pathways that promote cell proliferation or transformation. Research has investigated the possible roles of iron in this reactivity and the roles 

of released versus surface-borne iron.

Asbestos fibers can cause lipid peroxidation 

in mammalian cells and artificial membranes 

that can be prevented by removal of catalytic iron. Reduction of crocidolite cytotoxicity 

by certain antioxidants (including superoxide 

dismutase [SOD], a depletor of superoxide anion [SO]; catalase, a scavenger of hydrogen peroxide [H2O2]; dimethylthiourea [DMTU], a 

scavenger of the hydroxyl radical [•OH]; and 

desferroxamine, an iron chelator) suggested 

that iron is involved in the generation of ROS 

through a modified Haber-Weiss Fenton-type 

reaction resulting in the production of hydroxyl 

radical (e.g., from SO and H2O2 generated during phagocytosis) [Goodglick and Kane 1986; 

Shatos et al. 1987]. Such scavenging or chelation 

prevented DNA strand breakage in cells in vitro

by crocidolite fibers [Mossman and Marsh 1989].

In a cell-free study of five natural and two synthetic fibers, erionite, JM code 100 glass fibers, 

and glass wool were the most effective initiators of hydroxyl radical formation, followed 

by crocidolite, amosite, and chrysotile fibers. 

Hydroxyl radical formation activity showed 

positive correlations with tumor rates in rats 

challenged by intrapleural injection and with 

human mesothelioma mortality rates, but 

not with tumor rates in rats challenged by 

intraperitoneal injection [Maples and Johnson 1992]. SO-produced ROS then might induce DNA oxidative damage, measured as elevated 8-hydroxydeoxyguanosine (8-OHdG). 

In cell-free systems, the crocidolite-induced 

increase of 8-OHdG in isolated DNA was enhanced by addition of H2O2 and diminished by 

addition of desferroxamine [Faux et al. 1994]. 

However, de-ironized crocidolite fibers incubated in a cell-free system induced twice the 

8-OHdG oxidative damage to DNA as untreated crocidolite fibers. In parallel rat exposures, 

the combination of de-ironized crocidolite fibers plus Fe2O3 resulted in mesothelioma in all 

animals, whereas mesothelioma developed in 

only half the animals injected with crocidolite 

fibers alone and none of the animals injected 

with Fe2O3 alone [Adachi et al. 1994]. Other research suggested that unreleased fiber-surfacebound iron is important to the reactivity; 

long fibers of amosite and crocidolite both 

caused significant dose-dependent free radical damage to cell-free phage DNA, suppressible by the hydroxyl radical scavenger mannitol 

and by desferroxamine, but short RCFs and 

man-made vitreous fibers (MMVFs) did not, 

while releasing large quantities of Fe(III) iron 

[Gilmour et al. 1995]. Crocidolite fibers induced mutations in peritoneal tissue in vivo in 

rats, most prominently guanine-to-thymine 
50 NIOSH CIB 62 • Asbestos

(G-to-T) trans-versions known to be induced by 8-OHdG; this was interpreted as 

strong evidence for the involvement of ROS 

or reactive nitrogen species in crocidoliteinduced mutagenesis in vivo, consistent with 

in vitro and cell-free studies [Unfried et al. 

2002]. In contrast to glass fiber, crocidolite fiber intratracheal instillation in rats increased 

8-OHdG levels in DNA at one day and in its 

repair enzyme activity at seven days. This in 

vivo activity is consistent with asbestos- and 

MMVF-induced increases of 8-OHdG oxidative damage in vitro [Yamaguchi et al. 1999].

2.9.4.3.2 Membrane Interactions

Many mineral particles, elongate or not, can directly cause membranolysis or other cytotoxic 

responses without necessarily invoking extracellular generation of ROS. Mechanisms of cell 

damage by EMPs, independent of ROS formation, have been proposed to involve direct interactions of particle surface functional groups 

(e.g., silicon or aluminum or magnesium) with 

lipoproteins or glycoproteins of the cell membrane. It has been suggested that silica particle 

cytotoxicity to macrophages is due to distortion 

and disruption of secondary lysosomal membranes by phagocytosed particles whose surface 

silanol groups hydrogen-bond to membrane 

lipid phosphates, but that chrysotile-induced 

cellular release of hydrolytic enzymes is due to 

surface magnesium interacting ionically with 

sialic acid residues of membrane glycoproteins, 

inducing cation leakage and osmotic lysis [Allison and Ferluga 1977]. Chrysotile fibers cause 

lysis of red blood cells. EM indicates that cell 

membranes become wrapped around the fibers and that cell distortion and membrane 

deformation correlate with an increase in the 

intracellular ratio of sodium to potassium ions. 

Cell pretreatment with neuraminidase prevents fiber-cell binding, suggesting mediation 

by cell membrane glycoproteins [Brody and Hill 

1983]. However, chrysotile and crocidolite fibers both induced increased membrane rigidity in model unilamellar vesicles made of saturated dipalmitoyl phosphatidylcholine (DPPC), 

suggesting that lipid peroxidation is not involved in membrane rigidity induced by asbestos [Gendek and Brody 1990]. Silicate slate dust 

and chrysotile fibers both induced hemolysis 

in vitro and peroxidation of polyunsaturated membrane lipids. However, poly(2-vinylpyridine N-oxide) (PVPNO) and DPPC surface prophylactic agents suppressed lysis but 

not peroxidation, whereas SOD and catalase 

did the reverse; and lysis was much faster than 

peroxidation. This suggested that membrane lysis and peroxidation are independent processes [Singh and Rahman 1987]. However, either 

mechanism may be involved in membrane damage by EMPs; and seemingly disparate findings 

suggest uncharacterized details of EMP properties or of cellular or mineral conditioning under 

test conditions may be important.

In in vitro studies, quartz dust and chrysotile 

fibers induced loss of viability and release of lactate 

dehydrogenase (LDH) from alveolar macrophages. 

DPPC reduced these activities of the quartz but 

not of the asbestos [Schimmelpfeng et al. 1992]. 

DPPC is adsorbed from aqueous dispersion 

in approximately equal amounts on a surface 

area basis, about 5 mg phospholipid per square 

meter, by asbestos fibers [Jaurand et al. 1980] 

and by nonfibrous silicate particles [Wallace 

et al. 1992]; this is close to the value predicted 

by mathematical modeling of an adsorbed bilayer [Nagle 1993]. In the case of silica or clay 

membranolytic dusts, this adsorption fully suppresses their activity until toxicity is manifested 

as the prophylactic surfactant is digested from 

the particle surface by lysosomal phospholipase 

enzyme; mineral-specific rates of the process 

suggest a basis for differing fibrogenic potentials 
NIOSH CIB 62 • Asbestos 51

of different types of mineral particles [Wallace 

et al. 1992].

Samples of intermediate-length and shortlength NIEHS chrysotile were compared, with 

and without DPPC lung surfactant pretreatment, for micronucleus induction in Chinese 

hamster lung V79 cells in vitro. Increase in 

micronuclei frequency and multinuclear cell 

frequency were induced by all samples, with 

the greatest micronucleus induction by untreated intermediate-length chrysotile fibers 

and with greater activity for untreated versus 

treated short chrysotile fibers. Cell viability 

was greater for treated fibers [Lu et al. 1994]. 

NIEHS intermediate-length chrysotile was 

mildly acid-treated to deplete surface-borne 

magnesium while only slightly affecting fiber 

length. Challenge of Chinese hamster lung fibroblast cells in vitro for micronucleus induction found no significant difference between 

the treated and untreated samples, supporting a model of chemically nonspecific chromosomal and spindle damage effects [Keane et 

al. 1999]. Chrysotile fiber induction of mucin 

secretion in a tracheal cell culture was inhibited by using lectins to block specific carbohydrate residues on the cell surface; leached 

chrysotile was inactive, suggesting that the surface cationic magnesium of chrysotile was responsible for interaction with cell surface 

glycolipids and glycoproteins [Mossman et al. 

1983]. However, complete removal of accessible 

sialic acid residues from erythrocytes did not 

inhibit hemolysis by chrysotile fibers, suggesting that chrysotile fibers can induce lysis by interaction with some other component of the cell 

[Pelé and Calvert 1983].

2.9.4.3.3 Morphology-mediated Effects

A third possible mechanism for damage by EMP 

principally involves morphology. The possibility 

of frustrated phagocytosis is suggested by the 

Stanton hypothesis of an overriding significance 

of particle dimension for disease induction by 

durable EPs. A general concept is that EMPs 

longer than a phagocytic cell’s linear dimensions cannot be completely incorporated in a 

phagosome. Recruitment of membrane from the 

Golgi apparatus or endoplasmic reticulum may 

provide extensive addition to the plasma membrane for a cell’s attempted invagination to accommodate a long EMP in a phagosomal membrane [Aderem 2002]. However, because of the 

length of the EMP relative to the dimensions of 

the cell, the final phagosomal structure is topologically an annulus extending fully through the 

cell, rather than an enclosed vacuole fully within the cell. Following uptake of nonelongate particles, there is a maturation of the phagosomal 

membrane; the initial phagosomal membrane is 

that of the cell’s external plasmalemma, which 

cannot kill or digest phagocytosed material. After sealing of the fully invaginated phagosomal 

vesicle in the interior of the cell, there is a rapid and extensive change in the membrane composition [Scott et al. 2003]. This involves, in 

part, an association with lysosomal vesicles 

and exposure of particles within the secondary 

phagosome or phagolysosome to lytic enzymes 

and adjusted pH conditions. It is speculated 

that failure of the phagosome to close, as occurs 

in frustrated phagocytosis, induces dysfunction of the system. Conventional phagocytosis 

of nonelongate particles can lead to a respiratory or oxidative burst of membrane-localized 

NADPH oxidase of SO radicals, which may be 

converted to H2O2, hydroxyl radicals, and other toxic reactive products of oxygen. If these are 

released extracellularly in connection with frustrated phagocytosis, they are potentially harmful to the tissue [Bergstrand 1990].

Failure of normal phagocytosis to be completed may affect the duration or intensity 
52 NIOSH CIB 62 • Asbestos

of the phagocytic response. It may also affect 

the generation or release of reactive species 

or membranolytic digestive enzymes into the 

still-exterior annulus. Another possible effect 

is to alter the maturation of the annular frustrated phagocytic membrane from the normal structural and functional evolution of a 

closed phagolysosomal vesicle fully interior to 

the cell. Even in the response to such a frustrated phagocytosis, there might be some mineral 

specificity beyond morphology alone for EMPinduced release of reactive species. Amosite fibers, MMVF, silicon carbide fibers, and RCF-1 

fibers all stimulated modest release of SO that 

was not dose-dependent in isolated rat alveolar macrophages. However, when IgG, a normal 

component of lung lining fluid, was adsorbed 

onto the fiber surfaces, SO release was strongly enhanced for all but the silicon carbide fibers. 

SO release correlated with fibers’ IgG-adsorptive 

capacity, except for the amosite, which required 

only poorly adsorbed IgG for strong activity, suggesting some mineral specificity beyond 

morphology alone for the EMP-induced cellular respiratory burst [Hill et al. 1996].

2.9.4.3.4 Cellular Responses to Initiation 

of Toxicity

Subsequent to initiating damage by direct or induced ROS generation—by direct membranolysis 

generated by interactions of mineral surface 

sites with membrane lipids or glycoproteins, 

or by not-fully-defined toxic response to morphology-based frustrated phagocytosis—a standard model for consequent complex cellular response has evolved and has been the subject of 

extensive and detailed analyses [Mossman et 

al. 1997]. EMP-generated primary toxic stimuli to the cell are subject to signal transduction by 

mitogen-activated protein kinase (MAPK), beginning an intracellular multiple kinase signal 

cascade, which then induces transcription factors 

in the nucleus such as activator protein (AP)-1 or 

nuclear factor kappa beta (NF-κB), which in turn 

regulate the transcription of mRNA from genes 

for TNF-α or other cytokines involved in cell proliferation or inflammation.

Fibers of the six asbestos minerals generate 

MAPK in lung epithelium in vitro and in vivo, 

increasing AP-1 transcription activation, cell 

proliferation, death, differentiation, or inflammation. This is synergistic with cigarette smoke 

[Mossman et al. 2006]. Macrophage release of 

oxidants or mitogenic factors through such a 

pathway could then cause cell proliferation or 

DNA damage [Driscoll et al. 1998]. In contrast 

to MMVF-10 and RCF-4, amosite and two other 

carcinogenic fibers (silicon carbide and RCF-1) 

produced significant dose-dependent translocation of NF-κB to the nucleus in A549 lung epithelial cells. It was hypothesized that carcinogenic fibers have greater free radical activity, which 

produces greater oxidative stress and results in 

greater translocation of NF-κB to the nucleus 

for the transcription of pro-inflammatory genes 

(e.g., cytokines) [Brown et al. 1999]. Crocidolite 

induced AP-1 in vitro in JB6 cells and induced 

AP-1 transactivation in pulmonary and bronchial tissue after intratracheal instillation in transgenic mice, apparently mediated by activation of 

MAPK [Ding et al. 1999]. Chrysotile challenge 

to blood monocytes co-cultured with bronchial epithelial cells resulted in elevated levels in epithelial cells of protein-tyrosine kinase activity, 

NF-κB activity, and mRNA levels for interleukin 

(IL)-1β, IL-6, and TNF-α. Protein-tyrosine kinase activity, NF-κB activity, and mRNA synthesis were inhibited by antioxidants, suggesting 

ROS-dependent NF-κB-mediated transcription 

of inflammatory cytokines in bronchial epithelial cells [Drumm et al. 1999].

Chemokines known to be associated with particle-induced inflammation were found to be 
NIOSH CIB 62 • Asbestos 53

secreted by mesothelial cells after amosite challenge to cultured rat pleural mesothelial cells, 

and they were found in pleural lavage of rats 

challenged in vivo [Hill et al. 2003].

Fibers from crocidolite (asbestiform riebeckite) 

and EMPs from nonfibrous milled riebeckite 

increased phosphorylation and activity of a 

MAPK cascade in association with induction of 

an inflammatory state of rat pleural mesothelial 

cells and progenitor cells of malignant mesothelioma. Amelioration by preincubation with 

vitamin E indicated this to be an oxidative 

stress effect [Swain et al. 2004]. Lung lysate, 

cells from bronchoalveolar lavage, and alveolar macrophages and bronchiolar epithelial cells from lung sections from rats exposed 

to crocidolite or chrysotile fibers contained 

nitrotyrosine and phosphorylated extracellular 

signal-regulated kinases (ERKs); nitrotyrosine 

is a marker for peroxynitrile that activates 

ERK signaling pathways, altering protein function [Iwagaki 2003]. In vitro challenge of human bronchiolar epithelial cells with crocidolite 

or chrysotile fibers induced tissue factor (TF) 

mRNA expression and induced NF-κB and 

other transcription factors that bind the TF gene 

promoter. TF in vivo is involved in blood coagulation with inflammation and tissue remodeling [Iakhiaev et al. 2004]. Asbestos fibers activate an ERK pathway in vitro in mesothelial and 

epithelial cells. Crocidolite challenge to mice results in phosphorylation of ERK in bronchiolar 

and alveolar type II epithelial cells, epithelial cell 

hyperplasia, and fibrotic lesions. Epithelial cell 

signals through the ERK pathway lead to tissue 

remodeling and fibrosis [Cummins et al. 2003].

Crocidolite and erionite fibers, but not nonfibrous milled riebeckite, upregulated the expression of epidermal growth factor receptor 

(EGFR) in rat pleural mesothelial cells in vitro. 

Cell proliferation was co-localized subsequent 

to EGFR, suggesting initiation of a cell-signaling cascade to cell proliferation and cancer [Faux et al. 2000]. “Long” amosite fibers 

were more active than “short” amosite fibers in 

causing (1) damage to nude DNA; (2) in vitro

cytotoxicity in a human lung epithelial cell 

line; (3)  free radical reactions; (4)  inhibition 

of glycerol-6-phosphate dehydrogenase and 

pentose phosphate pathways; (5)  decrease in 

intracellular reduced glutathione; (6) increase 

in thiobarbituric acid reaction substances; and 

(7) leaking of LDH [Riganti et al. 2003].

An important paradox or seeming failure of 

in vitro studies concerns mesothelioma. Although chrysotile and amphibole asbestos fibers 

each clearly induce malignant mesothelioma 

in vivo, they do not transform primary human 

mesothelial cells in vitro, whereas erionite fibers 

do. Asbestos fibers can induce some genotoxic 

changes; crocidolite fibers induced cytogenotoxic 

effects, including increased polynucleated cells 

and formation of 8-OHdG in a phagocytic human mesothelial cell line, but did not induce 

cytogenotoxic effects in a nonphagocytic human promyelocytic leukemia cell line [Takeuchi 

et al. 1999]. Tremolite, erionite, RCF-1, and 

chrysotile fiber challenges of human-hamster 

hybrid A(L) cells showed chrysotile fibers to 

be significantly more cytotoxic. Mutagenicity was not seen at the hypoxanthine-guanine 

phosphoribosyltransferase (HPRT) locus for 

any of the fibers. Erionite and tremolite fibers 

induced dose-dependent mutations at the gene 

marker on the only human chromosome in the 

hybrid cell. Erionite was the most mutagenic 

type of fiber. RFC-1 fibers were not mutagenic, 

in seeming contrast to their known induction 

of mesothelioma in hamsters [Okayasu et al. 

1999]. Crocidolite fibers induced significant but 

reversible DNA single-strand breaks in transformed human pleural mesothelial cells, and 

TNF-α induced marginal increases; co-exposure 
54 NIOSH CIB 62 • Asbestos

to crocidolite fibers and TNF-α caused greater 

damage than fibers alone. Antioxidant enzymes 

did not reduce the DNA damage, suggesting a 

mechanism of damage other than by free radicals [Ollikainen et al. 1999]. Crocidolite fibers 

were also very cytotoxic to the cells; presumably, 

cell death may prevent the observation of cell 

transformation. In vitro challenge to mesothelial 

cells and to fibroblast cells by crocidolite fibers, 

but not by glass wool, induced dose-dependent 

cytotoxicity and increased DNA synthesis activity [Cardinali et al. 2006]. Crocidolite fibers were 

found to induce TNF-α secretion and receptors 

in human mesothelial cells, and TNF-α reduced 

cytotoxicity of crocidolite fibers by activating 

NF-κB and thus improving cell survival and permitting expression of cytogenetic activity [Yang 

et al. 2006]. Erionite fibers transformed immortalized nontumorigenic human mesothelial cells 

in vitro only when exposed in combination with 

IL-1β or TNF-α [Wang et al. 2004]. Erionite fibers were poorly cytotoxic but induced proliferation signals and a high growth rate in hamster 

mesothelial cells. Long-term exposure to erionite 

fibers resulted in transformation of human 

mesothelial cells in vitro, but exposure to asbestos fibers did not transform those cells [Bertino 

et al. 2007]. In vitro challenge of mesothelial cells 

to asbestos fibers induced cytotoxicity and apoptosis but not transformation. In vitro challenge 

of human mesothelial cells to asbestos fibers induced the ferritin heavy chain of iron-binding 

protein, an anti-apoptotic protein, with decrease 

in H2O2 and other ROS and resistance to apoptosis [Aung et al. 2007]. This was seen also in a human malignant mesothelial cell line.

The question of a co-carcinogenic effect of asbestos fibers with a virus has been raised. Most 

malignant mesotheliomas are associated with 

asbestos exposures, but only a fraction of exposed individuals develop mesothelioma, indicating that other factors may play a role. It has 

been suggested that simian virus 40 (SV40) and 

asbestos fibers may be co-carcinogens. SV40 is 

a DNA tumor virus that causes mesothelioma 

in hamsters and has been detected in several human mesotheliomas. Asbestos fibers appear to increase SV40-mediated transformation 

of human mesothelial cells in vitro [Carbone 

et al. 2002]. In an in vivo demonstration of 

co-carcinogenicity of SV40 and asbestos fibers, 

mice containing high copy numbers of SV40 

viral oncogene rapidly developed fast-growing 

mesothelioma following asbestos challenge. 

Transgenic copy number was proportional to 

cell survival and in vitro proliferation [Robinson et al. 2006].

Various mechanisms protect cells and tissues 

against oxidants, and it is conceivable that genetic and acquired variations in these systems may account for individual variation in 

the response to oxidative stress [Driscoll et al. 

2002]. Similarly, species differences in antioxidant defenses or the capacity of various defenses may underlie differences in response to 

xenobiotics that act, in whole or part, through 

oxidative mechanisms. Oxidative mechanisms 

of response to xenobiotics are especially relevant to the respiratory tract, which is directly and continually exposed to an external environment containing oxidant pollutants (e.g., 

ozone, oxides of nitrogen) and particles that 

may generate oxidants as a result of chemical properties or by stimulating production of 

cell-derived oxidants. In addition, exposure to 

particles or other pollutants may produce oxidative stress in the lung by stimulating the recruitment of inflammatory cells. For example, 

the toxicity of asbestos fibers likely involves the 

production of oxidants, such as hydroxyl radical, SO, and H2O2. Studies have also shown that 

asbestos fibers and other mineral particles may 

act by stimulating cellular production of ROS 

and reactive nitrogen species. In addition to 
NIOSH CIB 62 • Asbestos 55

direct oxidant production, exposure to asbestos and SVFs used in high-dose animal studies stimulates the recruitment and activation of 

macrophages and polymorphonuclear leukocytes that can produce ROS through the activity of NADPH oxidase on their cell membranes. 

Developing an understanding of the oxidative 

stress/NF-ĸB pathway for EMP-mediated inflammation and the interplay among exposureinduced oxidant production, host antioxidant 

defenses, and interindividual or species variability in defenses may be very important for 

appropriate risk assessments of inhaled EMPs 

[Donaldson and Tran 2002].

2.9.4.4 Studies Comparing EMPs from 

Amphiboles with Asbestiform 

versus Nonasbestiform Habits

Smith et al. [1979] compared tumor induction 

after IP injection in hamsters of two asbestiform 

tremolites, two nonasbestiform prismatic tremolitic talcs, and one tremolitic talc of uncertain asbestiform status. No tumors were observed following the nonasbestiform tremolite 

challenge, in contrast to the asbestiform tremolites. However, tumors were observed from 

the tremolitic talc of uncertain amphibole status. In rule-making, OSHA [1992] noted the 

small number of animals in the study, the early death of many animals, and the lack of systematic characterization of particle size and aspect ratio. Subsequent analyses (by chemical 

composition) performed on the nonasbestiform 

tremolitic talc from the study, which was not associated with mesothelioma, found 13% of particles had at least a 3:1 aspect ratio [Wylie et al. 

1993]. A prismatic, nonasbestiform tremolitic 

talc and an asbestiform tremolite from the study 

were analyzed for aspect ratio [Campbell et al. 

1979]. The researchers analyzed 200 particles of 

the asbestiform tremolite sample and found 17% 

had an aspect ratio of 3:1 or greater and 9.5% 

had an aspect ratio greater than 10:1. Analysis of 

200 particles of the prismatic tremolite showed 

that 2.5% (five EMPs) had an aspect ratio of 3:1 

or greater and 0.5% (one EMP) had an aspect ratio greater than 10:1.

Wagner et al. [1982] challenged rats by IP injection of tremolite asbestos, a prismatic nonasbestiform tremolite, or a tremolitic talc considered nonasbestiform containing a limited 

number of long fibers. Only the tremolite asbestos produced tumors; mesothelioma was found 

in 14 of 37 animals. The authors speculated that 

tumor rate may have risen further if the testing 

period had not been shortened due to infectioninduced mortality. Per microgram of injected 

dose, the asbestiform sample contained 3.3 × 

104 nonfibrous particles, 15.5 × 104 fibers, and 

56.1 × 103 fibers >8 μm long and <1.5 μm wide. 

Corresponding values for the prismatic amphibole were 20.7 × 104

, 4.8 × 104, and 0. Tremolitic 

talc values were 6.9 × 104, 5.1 × 104, and 1.7 × 

103. Infection-reduced survival prevented evaluation of a crocidolite-exposed positive control.

Another IP injection study with the rat used six 

samples of tremolite of different morphological 

types [Davis et al. 1991]. For three asbestiform 

samples, mesothelioma occurred in 100%, 97%, 

and 97% of exposed animals, at corresponding doses of 13.4 × 109 fibers with aspect ratio >3:1 per 121 × 106 fibers with length >8 μm 

and diameter <0.25 μm (100% of exposed animals); 2.1 × 109

 per 8 × 106 (97% of exposed animals); and 7.8 × 109

 per 48 × 106 (97% of exposed animals). For an Italian tremolite from 

a nonasbestos source and containing relatively few asbestiform fibers (1.0 × 109

 per 1 × 

106), mesothelioma was found in two-thirds of 

the animals, with delayed expression. For two 

nonasbestiform tremolites (0.9 × 109 per 0; 0.4 

× 109 per 0), tumors were found in 12% and 

5% of the animals, respectively; of these, and 
56 NIOSH CIB 62 • Asbestos

the response rate of 12% was above the expected background rate. The Italian sample resulting in 67% mesothelioma incidence contained 

only one-third the number of EMPs >8  μm 

long, in comparison with the nonasbestiform 

sample associated with 12% mesothelioma, and 

those two samples contained an approximately equal number of fibers with length >8  μm 

and width <0.5  μm. The preparations of the 

three asbestiform samples and the Italian sample were essentially identical. However, the two 

nonasbestiform samples associated with low 

mesothelioma incidence required significantly 

different pretreatment: the first required multiple washings and sedimentation, and the second, grinding under water in a micronizing 

mill. It was noted that those two nonasbestiform 

samples and the Italian sample contained minor 

components of long, thin asbestiform tremolite 

fibers. This study suggested that carcinogenicity may not depend simply on the number of 

EMPs, and the researchers called for methods 

of distinguishing “carcinogenic tremolite fibers” from nonfibrous tremolite dusts that contain similar numbers of EMPs of similar aspect 

ratios [Davis et al. 1991]. It has been suggested that the response observed for the Italian 

tremolite is of a pattern expected for a low dose 

of highly carcinogenic asbestos tremolite [Addison 2007].

A recent review of past studies of varieties of 

tremolite and the limitations of earlier studies 

(e.g., their use of injection or implantation versus inhalation) suggested that, on the basis of 

observed differences in the carcinogenicity of 

tremolite asbestos and nonasbestiform prismatic tremolite, differences in carcinogenicity of 

amphibole asbestos fibers and nonasbestiform 

amphibole cleavage fragments are sufficiently 

large to be discernable, even with the study limitations [Addison and McConnell 2008]. The 

authors also concluded the evidence supports 

a view that shorter, thicker cleavage fragments 

of the nonasbestiform amphiboles are less hazardous than the thinner asbestos fibers [Addison and McConnell 2008].

In summary, several types of animal studies have 

been conducted to assess the carcinogenicity and 

fibrogenicity of asbestiform and nonasbestiform 

tremolite fibers and other EMPs. Tremolite asbestos was found to be both fibrogenic and carcinogenic in rats by inhalation. However, the data 

for other particle forms of tremolite and for other amphiboles in general are much more limited 

and are based primarily on mesotheliomas produced by intrapleural administration studies in 

rats. Although these tests can be highly sensitive 

for specific material-tissue interactions, these 

studies bypass the lung entirely and thus provide no information on the test material’s potential for causing lung tumors. In addition, 

they have often been criticized for employing 

a nonphysiological route of administration. 

Some of the older studies [Smith et al. 1979; 

Wagner et al. 1982] are difficult to interpret 

because of inadequate characterization of the 

tremolite preparation that was used, although 

the studies do show fewer or no tumors from 

prismatic tremolite than from asbestiform 

tremolite when tested similarly. Unfortunately, 

doses used in most animal studies are generally reported in terms of mass (e.g., 10, 25, or 40 

mg/rat). Unless the test preparations are well 

characterized in terms of fiber counts and fiber size distributions, it is difficult to relate the 

mass-based dose in the animals to fiber count 

concentrations used to assess human occupational exposures. Where semiquantitative fiber 

count and size distribution data are provided, as 

in the study report by Davis et al. [1991], it is evident that the prismatic tremolite samples contain 

fewer particles >5 μm in length with an aspect 

ratio of >3:1 per 10-mg dose than the asbestiform 

tremolite samples, and the median particle 
NIOSH CIB 62 • Asbestos 57

widths are greater for the prismatic tremolite 

samples. Although the prismatic tremolite samples clearly generated fewer mesotheliomas than 

the asbestiform tremolite samples, it is not apparent whether the tumorigenic potency per EMP is 

lower for the nonasbestiform tremolites.

In a comparison of one asbestiform and two 

nonasbestiform tremolites, cellular in vitro assays for LDH release, beta-glucuronidase release, 

cytotoxicity, and giant cell formation showed relative toxicities that parallel the differences seen in 

an in vivo rat IP injection study of tumorigenicity 

using the same samples [Wagner et al. 1982]. 

In vitro cellular or organ tissue culture studies showed squamous metaplasia and increased 

DNA synthesis in tracheal explant cultures treated with long glass fibers or with crocidolite or 

chrysotile fibers, whereas cleavage fragments 

from their nonasbestiform analogues, riebeckite 

and antigorite, were not active [Woodworth 

et al. 1983]. For alveolar macrophages in vitro, 

crocidolite fibers induced the release of ROS 

at an order of magnitude greater than cleavage fragments from nonasbestiform riebeckite 

[Hansen and Mossman 1987]. Similar differences were observed in hamster tracheal cells for

• induction of ornithine decarboxylase, an 

enzyme associated with mouse skin cell 

proliferation and tumor promotion [Marsh 

and Mossman 1988]; 

• stimulating survival or proliferation in a 

colony-forming assay using those hamster tracheal epithelial cells [Sesko and 

Mossman 1989]; 

• activation of proto-oncogenes in tracheal 

epithelial and pleural mesothelial cells in 

vitro [Janssen et al. 1994]; and 

• cytotoxicity [Mossman and Sesko 1990].

A recent review concludes that a large body of 

work shows that cleavage fragments of amphiboles are less potent than asbestos fibers in a 

number of in vitro bioassays [Mossman 2008]. 

Several studies have investigated induction of 

molecular pathways in cells exposed to EMPs. 

The goals of such studies were to elucidate 

mechanisms involved in fiber-induced pathogenicity and to compare the relative potency of 

asbestiform and nonasbestiform EMPs. However, seemingly contradictory findings between 

some experiments suggest that improved methods for preparation of size-selected test particles and more extensive characterization of 

EMPs are needed. 

Although few animal studies of nonasbestiform 

amphibole dusts have been conducted, this research has revealed generally significant differences in pathogenicity between nonasbestiform 

and asbestiform amphiboles. There are few findings of biological effects or tumorigenicity induced by samples classified as nonasbestiform, 

and there are rational hypotheses as to the 

cause of those effects. There are general fundamental uncertainties concerning EMP properties and biological mechanisms that determine 

mineral particle toxicities and pathogenicities, 

specifically concerning the similarities or differences in disease mechanisms between EMPs 

from asbestiform versus nonasbestiform amphiboles. In vitro studies have generally shown 

differences in specific toxic activities between 

some asbestiform and nonasbestiform amphibole EMPs, although in vitro systems are 

not yet able to predict relative pathogenic risk 

for mineral fibers and other EMPs. This suggests a focus of research to determine if and 

when nonasbestiform amphibole EMPs are active for tumorigenicity or other pathology, if 

there is a threshold for those activities, and if 
58 NIOSH CIB 62 • Asbestos

distinguishing conditions or properties that 

determine such pathogenicity can be found.

2.9.5 Thresholds

Discussions of thresholds for adverse health 

effects associated with exposure to asbestos 

fibers and related EMPs have focused on the 

characteristics of dimension, including length, 

width, and the derived aspect ratio, as well as 

concentration. Although other particle characteristics discussed above may impact these 

thresholds or may have thresholds of their own 

that impact the toxicity of EMPs, they are not 

well discussed in the literature. The following 

discussion is focused on thresholds for dimension and concentration.

The seminal work of Stanton et al. [1981] laid 

the foundation for much of the information on 

dimensional thresholds. Their analyses showed 

that malignant neoplasms in exposed rats were 

best predicted by the number of EMPs longer 

than 8  μm and thinner than 0.25  μm. However, the number of EMPs in other size categories, having lengths greater than 4  μm and 

widths up to 1.5 μm, were also highly correlated with malignant neoplasms. Also, some samples with relatively larger proportions of shorter particles, such as the tremolites, produced 

high rates of tumors. Lippmann [1988, 1990] 

reviewed the literature and suggested that lung 

cancer is most closely associated with asbestos fibers longer than 10 μm and thicker than 

0.15 μm, whereas mesothelioma is most closely associated with asbestos fibers longer than 

5 μm and thinner than 0.1 μm. Evidence from 

animal studies and some in vitro studies suggests that short asbestos fibers (e.g., <5  μm 

long) may play a role in fibrosis but are of lesser concern than longer asbestos fibers for cancer development.

Berman et al. [1995] statistically analyzed aggregate data from 13 inhalation studies in 

which rats were exposed to 9 types of asbestos 

(4 chrysotiles, 3 amosites, 1 crocidolite, and 1 

tremolite asbestos) to assess fiber dimension and 

mineralogy as predictors of lung tumor and 

mesothelioma risks. Archived samples from the 

studies were reanalyzed to provide detailed information on each asbestos structure, including 

mineralogy (chrysotile, amosite, crocidolite, or 

tremolite), size (length and width, each in 5 categories), type (fiber, bundle, cluster, or matrix), 

and complexity (number of identifiable components of a cluster or matrix). Multiple concentrations (each for asbestos structures with 

different specified characteristics) were calculated for the experimental exposures. Although 

no univariate index of exposure adequately described lung tumor incidence observed across all 

inhalation studies, certain multivariate indices of 

exposure did adequately describe outcomes. Fibers and bundles longer than 5 μm and thinner 

than 0.4 μm contributed to lung tumor risk; very 

long (>40 μm) and very thick (>5 μm) complex 

clusters and matrices possibly contributed. Although structures <5 μm long did not contribute to lung tumor risk, potency of thin (<0.4 μm) 

structures increased with increasing length above 

5 μm, and structures >40 μm long were estimated to be about 500 times more potent than structures between 5 and 40 μm long. With respect to 

lung tumor risk, no difference was observed between chrysotile and amphibole asbestos. With 

respect to mesothelioma risk, chrysotile was 

found to be less potent than amphibole asbestos. 

Although the analysis of Berman et al. [1995] 

was limited to studies of asbestos exposure, similar statistical approaches may be adaptable to assess study outcomes from exposures to a broader 

range of EMPs, beyond asbestos.

In addressing the issue of a length threshold, the Health Effects Institute [HEI 1991] 
NIOSH CIB 62 • Asbestos 59

concluded that asbestos fibers <5 μm long appear to have much less carcinogenic activity 

than longer fibers and may be relatively inactive. A panel convened by ATSDR [2003] concluded that “given findings from epidemiological studies, laboratory animal studies, and in 

vitro genotoxicity studies, combined with the 

lung’s ability to clear short fibers, the panelists 

agreed that there is a strong weight of evidence 

that asbestos and SVFs shorter than 5 μm are 

unlikely to cause cancer in humans.” Also, an 

EPA [2003] peer consultant panel “agreed that 

the available data suggest that the risk for fibers 

<5 μm long is very low and could be zero.” They 

generally agreed that the width cutoff should 

be between 0.5 and 1.5 μm but deserved further analysis.

However, Dodson et al. [2003] have argued 

that it is difficult to rule out the involvement 

of short (<5  μm) asbestos fibers in causing 

disease, because exposures to asbestos fibers 

overwhelmingly involve fibers shorter than 

5 μm, and fibers observed in the lung and in 

extrapulmonary locations are also overwhelmingly shorter than 5  μm. For example, in a 

study of malignant mesothelioma cases, Suzuki 

and Yuen [2002] and Suzuki et al. [2005] found 

that the majority of asbestos fibers in lung and 

mesothelial tissues were shorter than 5  μm. 

Another study [Berman and Crump 2008a] 

showed that the best estimate for the potency 

of asbestos fibers between 5 and 10 μm is zero, 

but the hypothesis that these shorter fibers are 

not potent could not be rejected. Likewise, in 

no case could the hypothesis be rejected that fibers shorter than 5 μm are not potent.

NIOSH investigators have recently evaluated the relationship between the dimensions 

(i.e., length and width) of airborne chrysotile 

fibers and risks for developing lung cancer  or asbestosis, by updating the cohort of 

chrysotile-exposed textile workers previously studied by Dement et al. [1994], Stayner et 

al. [1997], and Hein et al. [2007]. Archived air 

samples collected at this chrysotile textile plant 

were reanalyzed by TEM to generate exposure 

estimates based on bivariate  fiber-size distribution [Dement et al. 2008]. TEM analysis of 

sampled fibers found all size-specific categories 

(35 categories were assigned, based on combinations of fiber width and length) to be highly 

statistically significant predictors of lung cancer and asbestosis [Stayner et al. 2007]. The 

smallest fiber size–specific category was thinner than 0.25 μm and <1.5 μm long. The largest 

size-specific category was thicker than 3.0 μm 

and >40 μm long. Both lung cancer and asbestosis were most strongly associated with exposures to thin fibers (<0.25 μm), and longer fibers (>10 μm) were found to be the strongest 

predictors of lung cancer. A limitation of the 

study is that cumulative exposures for the cohort were highly correlated across all fiber-size 

categories, which complicates the interpretation of the study results.

In addition to length and width, an important parameter used to define EMPs is the aspect ratio. The use of the 3:1 length:width aspect ratio as the minimum to define an EMP 

was not established on scientific bases such as 

toxicity or exposure potential. Rather, the decision was based on the ability of the microscopist to determine the elongate nature of a particle [Holmes 1965], and the practice has been 

carried through to this day. As bivariate analyses are conducted, the impact of aspect ratio, in 

addition to length and width, on toxicity and 

health outcomes needs to be addressed.

As discussed in Section 2.4.2, the nature of occupational exposures to asbestos has changed 

over the last several decades. Once dominated 

by chronic exposures in textile mills, friction 
60 NIOSH CIB 62 • Asbestos

product manufacturing, and cement pipe fabrication, current occupational exposures to asbestos in the United States are primarily occurring 

during maintenance activities or remediation 

of buildings containing asbestos. These current 

occupational exposure scenarios frequently involve short-term, intermittent exposures. The 

generally lower current exposures give added 

significance to the question of whether or not 

there is an asbestos exposure threshold below 

which workers would incur no risk of adverse 

health outcomes.

Risk assessments of workers occupationally exposed to asbestos were reviewed by investigators sponsored by the Health Effects Institute 

[1991]. They found that dose-specific risk is 

highly dependent on how the measurement of 

dose (exposure) was determined. A common 

problem with many of the epidemiological 

studies of workers exposed to asbestos is the 

quality of the exposure data. Few studies have 

good historical exposure data, and the available data are mostly area samples with concentrations reported as millions of particles per 

cubic foot of air (mppcf). Although correction 

factors have been used to convert exposures 

measured in mppcf to f/cm3, the conversions 

were often based on more recent exposure 

measurements collected at concentrations lower than those prevalent in earlier years. In addition, a single conversion factor was typically 

used to estimate exposures throughout a facility, which may not accurately represent differences in particle sizes and counts at different 

processes in the facility.

More recently, the concept of a concentration 

threshold has been reviewed by Hodgson and 

Darnton [2000]. It is generally accepted that 

lung fibrosis requires relatively heavy exposure to asbestos and that the carcinogenic response of the lung may be an extension of the 

same inflammatory processes that produce lung 

fibrosis. Some evidence for a threshold is provided by an analysis of a chrysotile-exposed cohort, which suggests a potential threshold dose 

of about 30  f/mL-yr to produce radiologically 

evident fibrosis [Weill 1994]. Another study of 

necropsy material from textile workers exposed 

to chrysotile shows a distinct step increase in fibrosis for exposures in the 20–30 f/mL-yr range 

[Green et al. 1997]. However, a study of textile 

mill workers exposed to chrysotile did not reveal 

evidence of significant concentration thresholds 

for either asbestosis or lung cancer [Stayner et 

al. 1997]. Hodgson and Darnton [2000] pointed 

out that any evidence suggesting a threshold for 

chrysotile would likely not apply to amphibole 

asbestos because radiologically evident fibrosis 

has been documented among workers exposed 

to amphibole asbestos at low levels (<5 f/mL-yr). 

They concluded that if a concentration threshold 

exists for amphiboles, it is very low.

For mesothelioma, Hodgson and Darnton [2000] 

identified cohorts with high rates of mesothelioma at levels of exposure below those at which increased lung cancer has been identified; in some 

studies, the proportion of mesothelioma cases 

with no likely asbestos exposure is much higher than expected. Hodgson and Darnton [2000] 

concluded that these studies support a nonzero 

risk, even from brief, low-level exposures.

Animal studies using intraperitoneal and intrapleural injection of asbestos fibers cited by Ilgren 

and Browne [1991] suggest a possible threshold 

concentration for mesothelioma. However, it is 

not clear how this would be useful to determine 

a threshold for inhalation exposure in humans.

2.10 Analytical Methods

Available analytical methods can characterize 

the size, morphology, elemental composition, 
NIOSH CIB 62 • Asbestos 61

crystal structure, and surface composition of 

bulk materials and individual airborne particles. There are two separate paradigms for selecting among these methods for their use or 

further development for application to EMPs: 

one is for their support of standardized surveys 

or compliance assessments of workplace exposures to EMPs; another is for their support of 

research to identify physicochemical properties of EMPs that are critical to predicting toxicity or pathogenic potential for lung fibrosis, 

lung cancer, or mesothelioma. The former refers to analytical methods that can be applied 

to samples of airborne particles, whereas the 

latter can be used to characterize airborne particles and bulk materials.

Cost, time, availability, standardization requirements, and other pragmatic factors limit the selection of analytical methods for standardized analysis of field samples for the first set of 

uses. Additionally, those uses require methods employed historically to establish exposureresponse relationships. Principal among these 

analyses for standardized industrial hygiene use 

is an optical microscopy method, PCM (e.g., 

NIOSH Method 7400 or equivalent) [NIOSH 

1994a]. Under the current NIOSH REL for airborne asbestos fibers, particles are counted 

if they are EMPs (i.e., mineral particles with 

an aspect ratio [length:width] of 3:1 or greater) of the covered minerals and they are longer than 5  μm when viewed microscopically 

according to NIOSH Method 7400 or its equivalent. The assumption when using this method is that all particles meeting the dimensional criteria are airborne asbestos fibers, because 

PCM cannot identify the chemistry or crystalline structure of a particle. This assumption may 

be appropriate in situations where the majority of particles are reasonably assumed to be one 

of the minerals covered by the airborne asbestos fiber REL. Electron microscopy can be used 

to determine the actual proportion of the total 

particles that are covered by the airborne asbestos fiber REL, and this proportion can be used 

to adjust the count from PCM (NIOSH Method 

7402) [NIOSH 1994b]. Such counts are known 

as PCM-equivalents, or PCMe. Note that this 

is not the same procedure as counting particles that would meet the PCM criteria under the 

electron microscope. Methods have been developed for performing counts under both scanning electron microscopy (SEM) [ISO 2002] 

and TEM [40 CFR§§ 763.A.E (2001)]. However, only a few countries (e.g., Germany, Austria, 

Netherlands, and Switzerland) use SEM routinely for counting.

Characterization of bulk minerals is a process 

known as petrographic analysis. Petrographic analysis includes a number of techniques, 

including polarized light microscopy (PLM), 

electron microscopy (SEM or TEM), X-ray diffraction (XRD), X-ray fluorescence (XRF), and 

electron microprobe analysis. Other techniques, 

such as infrared and Raman spectroscopy and 

surface area measurements, can also be used. 

Some of these techniques can also be applied to 

individual airborne particles. If it is determined 

that the toxicity of EMPs has a basis in properties that can be measured by one or more of 

these techniques, then it may be possible to tailor analytical procedures in the future to more 

precisely estimate risk.

Care should be taken in developing or applying 

new analytical methods to the analysis of asbestos for standardized and compliance assessments. The use of new or different analytical 

methods to assess exposures must be carefully evaluated and validated to ensure that they 

measure exposures covered by the health protection standard.

§§Code of Federal Regulations. See CFR in references.
62 NIOSH CIB 62 • Asbestos

One consideration in developing new methods 

for assessing workplace exposures is that silicate 

mineral particles thinner than the resolution of 

PCM in NIOSH Method 7400 are in the same 

size range as the deposition minimum observed 

for small particles in human respirable particle 

studies. Current standards for assessing particle 

dose are based on particle penetration into the 

human respiratory system, which may overestimate deposition [ISO 1995a]. More recently, proposals have been developed to account 

for deposition [Vincent 2005]. In addition, after depositing in the lung, a single asbestos fiber 

bundle can split into a great many individual fibrils. Accounting for this behavior may be important in developing methods that accurately 

represent risk from exposure.

It is also important to recognize that the sampling 

and analytical methods for assessing workplace 

exposures to EMPs have different constraints 

from methods used to assess environmental exposures. NIOSH is focused on developing and 

validating methods for assessing workplace exposures to EMPs and provides assistance in developing environmental exposure methods, where 

possible and appropriate, through its relationships with other federal agencies.

2.10.1 NIOSH Sampling and 

Analytical Methods for 

Standardized Industrial 

Hygiene Surveys

The analytical components of NIOSH’s REL for 

asbestos exposure take on substantial significance because the current REL was set on the 

basis of the limit of quantification (LOQ) of the 

PCM method with use of a 400-L sample, rather 

than solely on estimates of the health risk. Had 

a lower LOQ been possible, a lower REL may 

have been proposed to further reduce the risk 

of occupational cancer among asbestos-exposed 

workers. With advances in sampling pump capabilities—and if interference from other dust is 

not excessive—a lower limit of quantitation and 

thus a shorter averaging time for the REL may 

be possible.

PCM was designated as the principal analytical method for applying the REL because it 

was thought to be the most practical and reliable available method, particularly for field assessments. The particle counting rules specified for PCM analysis of air samples result in 

an index of exposure that has been used with 

human health data for risk assessment. PCMbased counts do not enumerate all EMPs because very thin particles, such as asbestos fibrils, are typically not visible by PCM when 

using NIOSH Method 7400. The ratio of 

countable EPs to the total number of EPs collected on air samples can therefore vary for 

samples collected within the same workplace, 

as well as between different workplaces where 

the same or different asbestos materials are 

handled [Dement and Wallingford 1990]. The 

result of this is that equivalent PCM asbestos 

exposure concentrations determined at different workplaces would be considered to pose 

the same health risk, when, in fact, those risks 

may be different because of unknown amounts 

of unobserved fibers on the samples. It is commonly stated that particles thinner than about 

0.2–0.25 μm typically cannot be observed with 

PCM because they are below the resolution 

limits of the microscope. However, the results 

for PCM counts may also vary according to the 

index of refraction of the material being examined. When the index of refraction of the particle is similar to that of the filter substrate or 

mounting medium, the ability to resolve particles is less than when the refractive index of 

the particle differs from that of the substrate 

[Kenny and Rood 1987]. When a microscope 
NIOSH CIB 62 • Asbestos 63

is calibrated appropriately for NIOSH Method 7400 and triacetin is used as the mounting 

medium, calculation and experiment have indicated that chrysotile fibers as thin as 0.15 μm 

can be resolved [Rooker et al. 1982], which implies that amphibole fibers thinner than 0.2 μm 

and with higher refractive index may actually 

be visible and potentially counted.

Individual asbestos fibrils range in width from 

<10 nm (0.01 μm) for chrysotile up to 40 nm 

(0.04  μm) or more for amosite. Thus, individual asbestos fibrils are not likely to be visible by PCM. Early studies suggested that asbestos particles of 3:1 aspect ratio and longer 

than 5 μm are not usually individual fibrils but 

fibrillar bundles that are much wider than fibrils [Hwang and Gibbs 1981; further data cited in Walton 1982], so that the number of particles meeting these criteria counted under 

PCM were not generally found to differ greatly 

from the number of particles meeting the same 

criteria counted under the electron microscope 

[Lynch et al. 1970; Hwang and Gibbs 1981; 

Marconi et al. 1984; Dement and Wallingford 

1990]. However, more recent studies suggest 

there is a substantial difference between counts 

of particles seen by PCM and TEM [Dement et 

al. 2009], and the importance of these differences in developing new methods to be used 

routinely for industrial hygiene surveys will be 

important to reconcile with the particle characteristics important in disease causation. 

Another aspect of NIOSH Method 7400 is that 

two sets of counting rules are specified, depending on the type of fiber analysis. The rules 

for counting particles for asbestos determination, referred to as the “A” rules, instruct the 

microscopist to count EPs of any width that are 

longer than 5 μm and have an aspect ratio of 

at least 3:1. However, EPs wider than 3 μm are 

not likely to reach the thoracic region of the 

lung when inhaled. The “B” counting rules, 

which are used to evaluate airborne exposure 

to other EPs, specify that only EPs thinner than 

3 μm and longer than 5 μm should be counted [NIOSH 1994a]. The European Union is 

moving toward a standardized PCM method 

for evaluating asbestos exposures with counting rules recommended by the World Health 

Organization (WHO), which specify counting 

only EPs thinner than 3 μm and with a 3:1 or 

larger aspect ratio [WHO 1997; European Parliament and Council 2003].

2.10.2 Analytical Methods

for Research

For research purposes, it may be important for 

a more expansive set of analyses to be considered. However, EMPs thinner than the limit of 

spatial resolution of the optical microscope are 

thought to be important etiologic agents for 

disease, so other detection and measurement 

methods may be needed for improved investigations of the relationship between fiber dimension and disease outcomes.

TEM has much greater resolving power than

optical microscopy, on the order of 0.001  μm. 

Additionally, TEM has the ability to semiquantitatively determine elemental composition by 

means of EDS. Incident electrons excite electronic states of atoms of the sample, and the atoms decay that excess energy either by emitting 

an X-ray of frequency specific to the element 

(X-ray spectroscopy) or by releasing a secondary electron with equivalent kinetic energy 

(an Auger electron). Furthermore, TEM can 

provide some level of electron diffraction (ED) 

analysis of particle mineralogy by producing a 

mineral-specific diffraction pattern based on 

the regular arrangement of the particle’s crystal structure [Egerton 2005].
64 NIOSH CIB 62 • Asbestos

The greater spatial resolving power and the 

crystallographic analysis abilities of TEM and 

TEM-ED are used in some cases for standardized workplace industrial hygiene characterizations. TEM methods (e.g., NIOSH 7402) 

are used to complement PCM in cases where 

there is apparent ambiguity in EMP identification [NIOSH 1994b] and, under the Asbestos Hazardous Emergency Response Act of 

1986, the EPA requires that TEM analysis be 

used to ensure the effective removal of asbestos 

from schools [EPA 1987]. Each of these methods employs specific criteria for defining and 

counting visualized fibers and reporting different fiber counts for a given sample. These data 

subsequently can be independently interpreted according to different definitional criteria, 

such as those developed by the International 

Organization for Standardization (ISO), which 

provides methods ISO 10312 and ISO 13794 

[ISO 1995b, 1999].

Improved analytical methods that have become 

widely available should be reevaluated for complementary research applications or for ease of 

applicability to field samples. SEM is now generally available in research laboratories and 

commercial analytical service laboratories. SEM 

resolution is on the order of ten times that of 

optical microscopy, and newly commercial field 

emission SEM (FESEM) can improve this resolution to about 0.01 μm or better, near that of 

TEM. SEM-EDS and SEM- wavelength dispersive spectrometers (WDS) can identify the elemental composition of particles. It is not clear 

that SEM-backscatter electron diffraction analysis can be adapted to crystallographic analyses equivalent to TEM-ED capability. The ease 

of sample collection and preparation for SEM 

analysis in comparison with TEM and some 

of the advantages of SEM in visualizing fields 

of EMPs and EMP morphology suggest that 

SEM methods should be reevaluated for EMP 

analyses, both of field samples and for research 

[Goldstein 2003].

Research on mechanisms of EMP toxicity includes concerns for surface-associated factors. 

To support this research, elemental surface 

analyses can be performed by scanning Auger spectroscopy on individual particles with 

widths near the upper end of SEM resolution. In 

scanning Auger spectroscopy, the Auger electrons stimulated by an incident electron beam 

are detected; the energy of these secondary 

electrons is low, which permits only secondary 

electrons from near-surface atoms to escape 

and be analyzed, thus analyzing the particle elemental composition to a depth of only one or a 

few atomic layers [Egerton 2005]. This method 

has been used in some pertinent research studies (e.g., assessing effects on toxicity of leaching 

Mg from chrysotile fiber surfaces) [Keane et al. 

1999]. Currently, this form of analysis is timeconsuming and not ideal for the routine analysis of samples collected in field studies.

Surface elemental composition and limited valence state information on surface-borne elements can be obtained by X-ray photoelectron 

spectroscopy (XPS or ESCA), albeit not for individual particles. XPS uses X-ray excitation of 

the sample, rather than electron excitation as 

used in SEM-EDS or TEM-EDS. The X-rays 

excite sample atom electrons to higher energy states, which then can decay by emission of 

photoelectrons. XPS detects these element-specific photoelectron energies, which are weak 

and therefore emitted only near the sample surface, similar to the case of Auger electron surface spectroscopy. In contrast to scanning Auger spectroscopy, XPS can in some cases provide 

not only elemental but also valence state information on atoms near the sample surface. However, in XPS the exciting X-rays cannot be finely focused on individual particles, so analysis 
NIOSH CIB 62 • Asbestos 65

is made of an area larger than a single particle 

[Watts and Wolstenholme 2003]. Thus, analysis 

of a mixed-composition dust sample would be 

confounded, so XPS is applicable only to some 

selected or prepared homogeneous materials or 

to pure field samples. 

2.10.3 Differential Counting 

and Other Proposed 

Analytical Approaches for 

Differentiating EMPs 

In assessments of asbestos fiber counts in 

mixed exposures, the use of PCM to determine concentrations of airborne fibers from 

asbestos minerals cannot ensure that EMPs 

from nonasbestiform minerals are excluded. 

No reliable, reproducible methods are available 

for analysis of air samples that would distinguish between asbestos fibers and EMPs from 

nonasbestiform analogs of the asbestos minerals. The lack of such validated analytical methods is clearly a major limitation in applying 

federal agencies’ definitions of airborne asbestos fibers. 

A technique referred to as differential counting, suggested as an approach to differentiate between asbestiform and nonasbestiform 

EMPs, is mentioned in a nonmandatory appendix to the OSHA asbestos standard. That 

appendix points out that the differential counting technique requires “a great deal of experience” and is “discouraged unless legally necessary.” It relies heavily on subjective judgment 

and does not appear to be commonly used 

except for samples from mines. In this technique, EMPs that the microscopist judges to be 

nonasbestiform (e.g., having the appearance 

of cleavage fragments) are not counted; any 

EMPs not clearly distinguishable as either asbestos or not asbestos in differential counting 

are to be counted as asbestos fibers. One effect 

of using differential counting is to introduce an 

additional source of variability in the particle 

counts, caused by different “reading” tendencies between microscopists. The technique has 

not been formally validated and has not been 

recommended by NIOSH.

For counting airborne asbestos fibers in mines 

and quarries, ASTM has proposed “discriminatory counting” that incorporates the concepts 

of differential counting. The proposed method uses PCM and TEM in a tiered scheme. Air 

samples are first analyzed by PCM. If the initial 

PCM fiber count exceeds the MSHA permissible exposure limit (PEL), TEM is performed 

to determine an equivalent PCM count of regulated asbestos fibers only. If the initial PCM 

count is greater than one-half the PEL but less 

than the PEL, discriminatory counting is then 

performed. Discriminatory counts are restricted to fiber bundles, fibers longer than 10 μm, 

and fibers thinner than 1.0 μm. If the discriminatory count is at least 50% of the initial PCM 

fiber count, TEM is performed to determine an 

equivalent PCM count of regulated asbestos fibers only. These results are then compared to 

regulatory limits [ASTM 2006].

ASTM has begun an interlaboratory study (ILS 

#282) to determine the interlaboratory precision of “binning” fibers into different classes 

based on morphology [Harper et al. 2007]. The 

first part of the validation process was to evaluate samples of ground massive or coarsely crystalline amphiboles and air samples from a taconite mine that have amphibole particulates, of 

which the majority are characterized as cleavage fragments. Almost none of the observed 

particles met the Class 1 criteria (i.e., potentially asbestiform on the basis of curved particles 

and/or fibril bundles). Many particles were classified as Class 2 (i.e., potentially asbestiform on 
66 NIOSH CIB 62 • Asbestos

the basis of length >10 μm or width <1 μm), although their morphology suggested they were 

more likely cleavage fragments. With use of alternate criteria for Class 2 (length >10 μm plus 

width <1 μm), the number of Class 2 particles 

was greatly reduced. However, evidence from 

the literature [Dement et al. 1976; Griffis et al. 

1983; Wylie et al. 1985; Siegrist and Wylie 1980; 

Beckett and Jarvis 1979; Myojo 1999] indicates 

that as many as 50% of airborne asbestos fibers 

are <10 μm long. The proportion of asbestos fibers in the length “bin” bracketed by 5 μm and 

10  μm was also quite large (about 30%), and 

the adoption of the alternate Class 2 criteria as 

length >10 μm and width <1 μm would cause 

this proportion of asbestos fibers to be classified 

as nonasbestiform and excluded from counts of 

asbestos fibers [Harper et al. 2008].

Other procedures have been suggested with 

the intent of ensuring that the counts on air 

samples do not include cleavage fragments 

[IMA-NA 2005; NSSGA 2005]. These procedures include reviewing available geological 

information and/or results from analysis of 

bulk materials to establish that asbestos is present in the sampled environment, or specifying 

dimensional criteria to establish that airborne 

particulates have population characteristics 

typical of asbestos fibers (e.g., mean particle 

aspect ratios exceeding 20:1).

For research purposes, it is critically important 

that an analytical method that clearly distinguishes between asbestiform and nonasbestiform 

EMPs be developed, validated, and used. Whether any of these suggested procedures would 

ensure adequate health protection for exposed 

workers is unclear, and the practical issues associated with implementing these supplemental procedures are also undetermined.

2.11 Summary of Key Issues

For asbestos fibers and other EMPs, an important question that remains unanswered 

is “What are the important dimensional and 

physicochemical determinants of pathogenicity?” Evidence from epidemiological and animal studies indicates that risks for asbestosis and lung cancer decrease with decreasing 

exposure concentration and that the potency 

of asbestos is reduced as the fiber length decreases. However, the results from lung burden 

studies indicate the presence of short asbestos 

fibers at disease sites, and positive correlations 

between lung cancer and exposure to short asbestos fibers make it difficult to rule out a role 

for short asbestos fibers in causing disease. 

Other areas of debate remain. For example, 

there is a continuing debate as to whether or 

not amphibole asbestos fibers are more potent 

lung carcinogens than chrysotile fibers. This 

possible greater potency has been postulated to 

result from slower dissolution (in lung, interstitial, and phagolysosomal fluids) of amphibole asbestos fibers compared to chrysotile fibers. Thus, amphibole asbestos fibers may tend 

to persist for longer periods in the lungs and 

other tissues, thereby imparting a greater potential to trigger carcinogenesis. A related issue 

that continues to be debated is the magnitude 

of the difference in potency for mesothelioma 

associated with types of asbestos fiber. 

Understanding the determinants of toxicity of 

asbestos fibers and other EMPs, as well as of 

nonelongate mineral particles such as quartz, 

may help to elucidate some of these issues. The 

human, animal, and in vitro studies performed 

to date have been on asbestos fibers and a limited number of nonasbestiform EMPs relative to 

the large and highly variable group of minerals 

to which there is potential exposure. Additional 
NIOSH CIB 62 • Asbestos 67

data are needed to more fully assess the particle characteristics that cause adverse health outcomes and to develop risk assessments.

Information on occupational exposures to nonasbestiform EMPs is limited, as is information 

on exposure to asbestos fibers and other EMPs 

in mixed-dust environments, making it difficult 

to assess the range of particle characteristics, 

including dimension, in occupational settings 

with exposures to nonasbestiform EMPs. The 

few studies that have assessed biopersistence or 

durability suggest that nonasbestiform EMPs are 

not as biopersistent as asbestiform fibers of the 

same length, but more information is needed 

to systematically assess the ranges and importance of biopersistence in determining toxicity. 

Any assessment of risk needs to address the influence of EMP dimensions, so studies that systematically compare, to the extent possible, the 

effects of asbestiform and nonasbestiform particles of similar dimensions and dosimetrics—

such as particle count, disaggregation, and 

surface area—from the same mineral (e.g., 

crocidolite and nonasbestiform riebeckite) are 

needed for a variety of mineral types. Ultimately, management of risk needs to be based 

on an understanding of the estimated quantitative risk from exposures to various EMPs and 

on an understanding of the concentrations and 

particle characteristics of the various EMPs to 

which humans are or could be exposed and the 

exposures in occupational and other settings. 

An important need is to identify and develop 

analytical methods that can be used or modified to quantify occupational exposures to 

EMPs of toxicological importance and that are 

capable of differentiating EMPs on the basis of 

particle characteristics demonstrated to be important in causing disease. The current PCM 

method is inadequate for assessing exposures 

to fibers in mixed-dust environments, and 

it lacks the capability to measure all the important physical and chemical parameters of 

EMPs thought to be associated with toxicity. 

The feasibility of using EM methods will need 

to be addressed if they are to replace the PCM 

method. Until these issues are addressed, improvements in PCM methodologies should be 

pursued. In epidemiological and toxicological 

research, EM methods will need to be used to 

carefully characterize the exposure materials. 

Also, the results of toxicological and epidemiological studies may identify additional particle 

characteristics that warrant further evaluation 

to determine whether they can be incorporated into sampling and analytical methods used 

to assess worker exposures. 

Section 3 of this Roadmap presents a framework for proposed research intended to address these scientific issues and inform future 

public health policies and practices. 

NIOSH CIB 62 • Asbestos 69

3 Framework for Research

3.1 Strategic Research Goals and Objectives

Strategic goals and objectives for a multidisciplinary research program on mineral fibers 

and other EMPs are identified below. Shown in 

brackets following each goal and objective is the 

number of the section of this Roadmap in which 

the goal or objective is subsequently discussed.

I. Develop a broader understanding of the important determinants of toxicity for 

asbestos fibers and other EMPs [3.2].

• Conduct in vitro studies to ascertain what physical, chemical, surface properties, 

and other particle characteristics influence the toxicity of asbestos fibers and other 

EMPs [3.2.1]; and

• Conduct animal studies to ascertain what physical and chemical properties, surface 

properties, and other particle characteristics influence the toxicity of asbestos fibers 

and other EMPs [3.2.2].

II. Develop information and knowledge on occupational exposures to asbestos fibers 

and other EMPs and related health outcomes [3.3].

• Assess available occupational exposure information relating to various types of 

asbestos fibers and other EMPs [3.3.1];

• Collect and analyze available information on health outcomes associated with 

exposures to various types of asbestos fibers and other EMPs [3.3.2]; 

• Conduct selective epidemiologic studies of workers exposed to various types of 

asbestos fibers and other EMPs [3.3.3]; and

• Improve clinical tools and practices for screening, diagnosis, treatment, and 

secondary prevention of diseases caused by asbestos fibers and other EMPs [3.3.4].
70 NIOSH CIB 62 • Asbestos

3.2 An Approach to Conducting 

Interdisciplinary Research

Within each of the goals and objectives laid out 

in this framework, a more detailed research 

program will have to be developed. Research to 

support these three goals must be planned and 

conducted by means of an interdisciplinary approach, incorporating toxicological, epidemiological, exposure assessment, medical, analytical, and mineralogical methods. The research 

must also be integrated to optimize resources, 

facilitate the simultaneous collection of data, 

and ensure, to the extent feasible, that the research builds toward a resolution of the key issues. An aim of the research is to acquire a level 

of mechanistic understanding that can provide 

the basis for developing biologically-based 

models for extrapolating results of animal inhalation and other types of in vivo studies to exposure conditions typically encountered in the 

workplace. The information gained from such 

research can then be used by regulatory agencies and occupational health professionals to 

implement appropriate exposure limits and risk 

management programs for monitoring worker 

exposure and health. Much of this research may 

be accomplished by NIOSH, other federal agencies, or other stakeholders. Any individual research project undertaken should be designed 

to ensure that the results can be interpreted and 

applied within the context of other studies in the 

overall program and lead to outcomes useful for 

decision-making and policy-setting. 

3.3 National Reference 

Repository of Minerals and 

Information System

To support the needed research, a national reference repository of samples of asbestos and related minerals will be required, and a database 

of relevant information should be developed. 

Minerals vary in composition and morphology 

by location and origin, and differences within the 

same mineral type can be significant. Currently, 

no national repository exists to retain, document, and distribute samples of asbestiform and 

nonasbestiform reference minerals for research 

and testing. These reference samples should be 

well-characterized research-grade materials that 

III. Develop improved sampling and analytical methods for asbestos fibers and other 

EMPs [3.4].

• Reduce inter-operator and inter-laboratory variability of the current analytical 

methods used for asbestos fibers [3.4.1];

• Develop analytical methods with improved sensitivity to visualize thinner EMPs to 

ensure a more complete evaluation of airborne exposures [3.4.2];

• Develop a practical analytical method for air samples to differentiate between 

exposures to asbestiform fibers from the asbestos minerals and exposures to EMPs 

from their nonasbestiform analogs [3.4.3];

• Develop analytical methods to assess durability of EMPs [3.4.4]; and

• Develop and validate size-selective sampling methods for EMPs [3.4.5].
NIOSH CIB 62 • Asbestos 71

are made available to the research community 

for testing and standardization. This will allow 

minerals with matching properties (e.g., morphology, dimension) to be chosen for study. To 

accomplish this research, exhaustive characterization of the samples, including contaminants, 

is necessary. Detailed characterizations of minerals should include their ability to affect biological activities and properties such as (1) purity, 

(2) particle morphology (range of dimensions 

and sizes), (3) surface area, (4) surface chemistry, and (5) surface reactivity. The particle characteristics identified by Hochella [1993] should 

be considered for particle characterization. The 

use of these samples in research would facilitate 

meaningful comparisons and reduce uncertainties in the interpretation of results between and 

among studies.

Care must be taken to ensure that a sufficient 

amount of the studied material is available, not 

only for current studies, but also as reference material for possible future studies. The repository 

should accept and store samples from researchers conducting EMP studies so that further testing and characterizations can be performed. The 

information developed from all of these efforts 

should be entered into a database, which can 

serve as a tool for selection of minerals for testing and validation of toxicological tests, as well 

as to assist in identification of worker populations for possible epidemiological studies. 

The development of a comprehensive, publicly 

available information system incorporating all 

studies of the toxicity, exposures, and health 

effects of asbestos and related minerals could 

help enhance the development of the research 

programs, avoid duplication of effort, and enhance interpretation of the data generated. The 

system should include all pertinent information about methods, doses or exposures, minerals, particle characteristics, and other topics. 

3.4 Develop a Broader 

Understanding of the 

Important Determinants of 

Toxicity for Asbestos Fibers 

and Other EMPs

To address this objective, one of the first steps 

will be to identify the range of minerals and mineral habits needed to systematically address the 

mineral characteristics that may determine particle toxicity. Care must be taken to ensure that 

mineralogical issues in a study are adequately addressed. Information on both crystalline lattice 

structure and composition is needed to define a 

mineral species, because information on either 

alone is insufficient to describe the properties of 

a mineral. For example, nonasbestiform riebeckite and asbestiform riebeckite (crocidolite) share 

the same elemental composition but have different expressions of their crystalline lattices. EMPs 

from nonasbestiform riebeckite are not flexible. 

Crocidolite fibers generally have chain-width defects, which explain their flexibility. These chainwidth defects also affect diffusion of cations and 

dissolution properties, both of which can explain 

greater release of iron into surrounding fluid by 

crocidolite than by nonasbestiform riebeckite 

[Guthrie 1997]. 

In addition to elemental content and crystalline habit, the particle characteristics identified by Hochella [1993] should be considered 

for particle characterization. For example, the 

current paradigm for fiber pathogenicity does 

not discriminate between different compositions of biopersistent fibers, except insofar as 

composition determines biopersistence. Two 

biopersistent fiber types, erionite [Wagner et 

al. 1985] and silicon carbide [Davis et al. 1996], 

show a special proclivity to cause mesothelioma, for reasons that are not easily explained by 
72 NIOSH CIB 62 • Asbestos

the current paradigm because their biopersistence and distributions of fiber lengths are not 

substantially different from those of the amphiboles. The biochemical basis of the enhanced 

pathogenicity of these two fiber types has not 

been elucidated. This suggests that some fiber 

types may possess surface or chemical reactivity that imparts added pathogenicity over and 

above what would be anticipated for long biopersistent fibers. Because of the many variations 

in elemental composition, crystalline structure, and other characteristics of these minerals, it will be impossible to study all variants. 

Therefore, a strategy will need to be developed 

for selecting minerals for testing. This strategy 

should include consideration of occupationally 

relevant minerals and habits in order to complement available information, availability of 

appropriate and well-characterized specimens 

for testing, and practical relevance of the results 

to be achieved through testing. 

EPA’s Office of Pollution Prevention and Toxics, NIEHS, NIOSH, and OSHA assembled an 

expert panel in the 1990s to consider major issues in the use of animal models for chronic 

inhalation toxicity and carcinogenicity testing 

of thoracic-size elongate particles. Issues considered included the design of animal tests of 

chronic inhalation exposure to EMPs; preliminary studies to guide them; parallel mechanistic studies to help interpret study results and 

to extrapolate findings with regard to potential 

health effects in humans; and available screening tests for identifying and assigning a priority 

for chronic inhalation study. There was general 

agreement that (1) chronic inhalation studies of 

EMPs in the rat are the most appropriate tests 

for predicting inhalation hazard and risk of 

EMPs to humans; (2) no single assay or battery 

of short-term assays could predict the outcome 

of a chronic inhalation bioassay for carcinogenicity; and (3) several short-term in vitro and in 

vivo studies may be useful to assess the relative 

potential of various EMPs to cause lung toxicity 

or carcinogenicity [Vu et al. 1996]. 

Such short-term assays and strategies were considered by an expert working group assembled 

by the International Life Sciences Institute’s 

Risk Science Institute to arrive at a consensus 

on current assays useful for screening EMPs 

for potential toxicity and carcinogenicity [ILSI 

2005]. Dose, dimension, durability, and possible surface reactivities were identified as critical parameters for study, although it was noted 

that no single physicochemical property or 

mechanism can now be used to predict carcinogenicity of all EMPs. The strategy for shortterm (i.e., 3 months or less) testing in animal 

models included sample preparation and characterization (composition, crystallinity, habit, 

size distribution); testing for biopersistence in 

vivo with use of a standard protocol such as 

that of the European Union [European Commission 1999]; and a subchronic inhalation or 

instillation challenge of the rat, with evaluation 

of lung weight and fiber burden, bronchoalveolar lavage profile, cell proliferation, fibrosis, and 

histopathology. Additionally, other nonroutine 

analyses for particle surface area and surface reactivities and short-term in vitro cellular toxicological assays might be evaluated. The use of in 

vitro tests should be tempered by the observations that standard protocols fail to distinguish 

relative pathogenic potentials of even nonelongate silicates (such as quartz versus clay dusts) 

and that treatment of particle surfaces (such as 

modeling their conditioning upon deposition 

on the lipoprotein-rich aqueous hypophase 

surface of the deep lung) can greatly affect their 

expression of toxicities [ATSDR 2003]. 

EMPs encountered in any particular work environment are frequently heterogeneous, which 

limits the ability of epidemiological and other 
NIOSH CIB 62 • Asbestos 73

types of health assessment studies to evaluate 

the influence on toxicity of EMP dimensions 

(length and width), chemical composition, biopersistence, and other characteristics. Toxicological testing is needed to address some of the 

fundamental questions about EMP toxicity that 

cannot be determined through epidemiology or 

other types of health assessment studies. Irrespective of study type or design, the full characterization of all particulate material in a test 

sample is an essential step in understanding 

the mechanisms of EMP toxicity. The determination of EMP dimensions is important, and 

they are best expressed as bivariate size distributions (i.e., width and length). Such determinations should be made by using both relatively simple procedures (optical microscopy) 

and highly specialized techniques (e.g., TEM 

or SEM with EDS), because size-specific fractions of EMP exposures have both biological 

and regulatory significance. 

The chemical composition (e.g., intrinsic chemical constituents and surface chemistry) of asbestos fibers and other EMPs has been shown 

to have a direct effect on their ability to persist 

in the lung and to interact with surrounding 

tissue to cause DNA damage. For example, ferric and ferrous cations are major components 

of the crystalline structure of amphibole asbestos fibers; iron may also be present as a surface 

impurity on chrysotile asbestos fibers and other EMPs. The availability of iron at the surface 

of asbestos fibers and other EMPs has been 

shown to be a critical parameter in catalyzing the generation of ROS that may indirectly 

cause genetic damage [Kane 1996]. Also, attempted clearance of long asbestos fibers from 

the lung causes frustrated phagocytosis, which 

stimulates the release of ROS [Mossman and 

Marsh 1989]. Individual adaptive responses 

to oxidant stress and the body’s ability to repair damaged DNA are dependent on multiple 

exogenous and endogenous factors, but few 

experiments have been attempted to evaluate these variables in animal or human model 

systems. Kane [1996] has suggested that the 

mechanisms responsible for the genotoxic effects of asbestos fibers are due to indirect DNA 

damage mediated by free radicals and direct 

physical interference with the mitotic apparatus by the fibers themselves. Research to address the following questions would assist in 

validating these proposed mechanisms: 

• Are in vitro genotoxicity assays relevant 

to carcinogenesis of asbestos fibers and 

other EMPs?

• Are in vitro doses relevant for in vivo exposures?

• Can genotoxic effects of asbestos fibers 

and other EMPs be assessed in vivo?

Macrophages are the initial target cells of EMPs 

and other particulates deposited in the lungs 

or pleural and peritoneal spaces. Phagocytosis of asbestos fibers has been shown to be accompanied by the activation of macrophages, 

which results in the generation of ROS as well 

as a variety of chemical mediators and cytokines [Kane 1996]. These mediators amplify 

the local inflammatory reaction. Persistence 

of asbestos fibers in the lung interstitium or 

in the subpleural connective tissue may lead 

to a sustained chronic inflammatory reaction 

accompanied by fibrosis [Oberdorster 1994]. 

The unregulated or persistent release of these 

inflammatory mediators may lead to tissue 

injury, scarring by fibrosis, and proliferation 

of epithelial and mesenchymal cells. This response appears to occur independently of fiber 

length. In the lungs and pleural linings, chronic inflammation and fibrosis are common reactions following exposure to asbestos fibers, but 

research is needed to understand the effects of 

fiber dimension, loading, and surface reactivity 
74 NIOSH CIB 62 • Asbestos

on the development of disease endpoints such 

as inflammation, fibrosis, and cancer.

It has been suggested that asbestos fibers and 

other EMPs may contribute to carcinogenesis 

by multiple mechanisms and that EMPs may act 

at multiple stages in neoplastic development, 

depending on their physicochemical composition, surface reactivity, and biopersistence in the 

lung [Barrett 1994]. Animal inhalation studies 

are needed to investigate the biopersistence and 

toxicity of asbestos fibers and other EMPs representing a range of chemical compositions and 

morphological characteristics (including crystalline habits) and representing a range of discrete lengths and widths. An additional factor 

that should be considered and evaluated is the 

influence of concurrent exposure to other particles and contaminants on the biopersistence 

and toxicity of EMPs. In a recently reported 

short-term (5-day) animal inhalation study to 

evaluate the biopersistence of chrysotile fibers 

with and without concurrent exposure to joint 

compound particles (1–4 μm MMAD), the 

clearance half-time of all fiber sizes was approximately an order of magnitude less for the group 

exposed to chrysotile and joint-compound particles [Bernstein et al. 2008]. Histopathological 

examination indicated that the combination of 

chrysotile and fine particles accelerated the recruitment of alveolar macrophages, resulting in 

a 10-fold decrease in the number of fibers remaining in the lung. Although no mention was 

made of any pathological changes in the lungs of 

the chrysotile/particulate-exposed group, other 

studies have shown that the recruitment of macrophages then increases the production and recruitment of polymorphonuclear leukocytes, 

which themselves can generate ROS [Driscoll et 

al. 2002; Donaldson and Tran 2002]. 

Much research has been focused on lung cancer and mesothelioma. Even if it is determined 

that EMPs from some minerals have low potency for causing cancer, additional studies 

may be needed to investigate their potential for 

causing inflammation, fibrosis, and other nonmalignant respiratory effects. Also, the relationship between EMP dimension and fibrosis 

should be more fully investigated. The results 

of such research may allow currently used standard exposure indices to be modified by specifying different dimensional criteria (lengths 

and widths) relevant to each of the disease outcomes associated with EMP exposures, and by 

determining whether biopersistence should be 

included as an additional criterion. However, 

this research may be dependent on the development of new technology that can generate 

mineral fibers and other EMPs of specific dimensions in sufficient quantities to conduct 

animal inhalation experiments. Consequently, 

the development of revised exposure indices 

based on EMP dimension may not be possible 

in the short term.

The research strategy described above should 

conform with the general strategies and tactics 

that have been recommended by several expert 

panels for clarifying the risks and causes of asbestos exposure–associated diseases and with the 

current effort of the U.S. Federal Government Interagency Asbestos Working Group (IAWG), involving participation of the EPA, USGS, NIOSH, 

ATSDR, CPSC, OSHA, MSHA, and NIEHS/

NTP, to identify federal research needs and possible actions regarding asbestos fibers and other 

durable EMPs of public health concern [Vu et al. 

1996; ILSI 2005; Schins 2002; Greim 2004; Mossman et al. 2007].

An ILSI Risk Science Institute Working Group 

supported by EPA published a tiered testing 

strategy for fibrous particles in 2005 [ILSI 2005]. 

Consideration should be given to the following 

slight modification of this published scheme. 
NIOSH CIB 62 • Asbestos 75

Noteworthy in the findings of the ILSI Working Group report is the inadequacy of in vitro

test models to predict the in vivo toxicity of 

EMPs. Indeed, many man-made mineral fibers 

are positive in cell test systems but do not cause 

fibrosis or cancer in chronic animal models. 

The in vitro test systems lack predictive ability 

because they do not incorporate biopersistence. 

For this reason, in vitro tests, other than assays 

for durability, are not included in the tiered testing strategy given below. 

Step 1. Preparation and characterization 

of test EMPs

This is the initial, required step for any toxicological evaluation. It should include

• comprehensive chemical and mineralogical characterization, including crystallinity and EMP habit.

• size distribution of the EMPs found in the 

workplace (total particulate sample), as 

well as dimensional characteristics of sizeselected fraction(s) to be used for hazard 

evaluation. A limiting step for detailed toxicological evaluation is the availability of 

sufficient quantities of size-selected EMPs 

of known chemistry and mineralogy. 

Step 2. Assessment of in vitro durability

Evidence indicates that highly soluble fibrous 

particles do not exhibit fibrotic or carcinogenic 

potential in animal studies. Rate of dissolution in 

simulated body fluids should be measured with 

a dynamic flow-through system, as outlined by 

Potter et al. [2000]. In brief, EMPs are exposed 

by continuous flow to a modified Gamble’s solution, and fiber diameter is monitored optically 

over time. Biopersistence would be an indication of concern and would indicate the need for 

further testing of the pathogenic potential of the 

EMP. This step is optional, as one could move 

directly to Step 3. 

Step 3. Short-term in vivobiopersistence test

Biopersistence of fibers longer than 20 μm has 

been found to be an excellent predictor of collagen deposition in chronic inhalation studies 

[Bernstein et al. 2001]. Two alternative methods are accepted by the European Commission 

[1997]: intratracheal instillation and 5-day 

inhalation by rats. It is recommended that fiber burden be measured at time points up to 

3 months post-exposure. Biopersistence would 

be an indication of concern and would indicate 

the need for further testing of the pathogenic 

potential of the EMP.

Step 4. Subchronic inhalation study

Parameters that should be measured in such 

an inhalation study are noted by EPA [2001]. 

The test should involve inhalation exposure 

for 3 months and should evaluate pulmonary 

responses over 6 months post-exposure. Responses to be measured should include biopersistence, persistent inflammation, cell proliferation (bromodeoxyuradine [BrdU] assay), 

fibrosis, epithelial cell hyperplasia, lung weight, 

and fiber burden. Biopersistence and persistent 

inflammation are notable markers of concern. 

If the subchronic study is positive, a long-term 

inhalation study is necessary to conduct a fullrisk assessment. 

Step 5. Long-term inhalation study

The test would include a 2-year inhalation 

study in rats, with lifelong follow-up. Fibrosis, lung tumors, and mesothelioma should be 

measured according to EPA guidelines [EPA 

2001] for long-term inhalation studies of fibers. Obtainment of lung burden, dose-related 
76 NIOSH CIB 62 • Asbestos

response, and time-course data would enable 

risk assessment.

Implicit in any new or revised occupational 

health policy for EMPs would be the need to 

conduct appropriate assessments of risk. Risk 

assessments for lung cancer, mesothelioma, 

and asbestosis have been conducted on worker 

populations exposed to various asbestos minerals. These risks have been qualitatively confirmed in animals, but no adequate quantitative 

multidose inhalation studies with asbestos have 

been conducted in rodents that would permit 

direct comparisons to lung cancer and mesothelioma risks determined from exposed human populations. Given the availability of risk 

estimates for lung cancer in asbestos-exposed 

humans, chronic studies with rats exposed to 

asbestos (e.g., chrysotile) fibers would provide 

an assessment of the rat as a valid “predictor” 

of human lung cancer risks associated with exposure to asbestos fibers and other EMPs.

3.4.1 Conduct In Vitro Studies to 

Ascertain the Physical and 

Chemical Properties that 

Influence the Toxicity of 

Asbestos Fibers and Other EMPs

Although in vitro studies may not be appropriate for toxicology screening tests of EMPs, they 

can help clarify the mechanisms by which some 

EMPs induce cancer, mesothelioma, or fibrosis, 

as well as the properties of EMPs and conditions of exposure that determine pathogenicity. In vitro studies allow specific biological and 

mechanistic pathways to be isolated and tested 

under controlled conditions that are not feasible 

in animal studies. In vitro studies can yield data 

rapidly and provide important insights and confirmations of mechanisms, which can be confirmed with specifically designed in vivo studies. 

With the exception of in vitro genotoxicity 

testing of asbestos fibers, little testing information is available on the potential genotoxicity 

of EMPs. In contrast to standard genotoxicity 

testing of soluble substances, the results from 

testing EMPs can be influenced by dimension, surface properties, and biopersistence. The 

mechanisms of asbestos-induced genotoxicity 

are not clear, but direct interaction with the 

genetic material and indirect effects via production of ROS have been proposed. A combination of the micronucleus test and the comet 

assay with continuous treatment (without exogenous metabolic activation) has been reported 

to detect genotoxic activity of asbestos fibers 

[Speit 2002]. However, further research is needed to determine whether this approach is applicable for genotoxicity testing of other EMPs. 

Before conducting such studies, the following 

EMP interactions should be addressed:

• initial lesions evoking cell damage or response (e.g., direct or indirect cytotoxic 

or genotoxic events or induction of toxic 

reactive intermediate materials);

• subsequent multistage cellular response 

(e.g., intracellular signaling through a kinase cascade to nuclear transcription of 

factors for apoptosis, cell transformation, 

and cell or cell system proliferation or remodeling and initiation or promotion of 

neoplasia or fibrosis); and 

• critical time-course events in those processes (e.g., cell-cycle-dependent EMP interactions or EMP durability under different phagocytic conditions).

Capabilities for conducting these studies improved during the 2000s, including

• advancement in analytical methods for 

physicochemical characterization of 

EMP properties (e.g., for resolving small 
NIOSH CIB 62 • Asbestos 77

dimensions and nanoscale surface properties); and 

• ability to prepare EMP samples that are 

“monochromatic” in size or surface properties in quantities sufficient for well-controlled in vitro assays.

Identification of the initiating EMP-cell interactions calls for research on the mechanisms of 

• cell-free generation of toxic ROS by EMPs 

or EMP-induced cellular generation of 

toxic ROS; and

• direct membranolytic, cytotoxic, or genotoxic activities of the EMP surface in contact 

with cellular membranes or genetic material. 

These investigations will require attention to the 

following:

• effects of EMP surface composition (e.g., 

surface-borne iron species); 

• effects of normal physiological conditioning of respired particles (e.g., in vitro modeling of in vivo initial conditioning of EMP 

surfaces by pulmonary surfactant);

• nonphysiological conditioning of EMP under in vitro test conditions (e.g., by components of nutrient medium);

• cell type (e.g., phagocytic inflammatory 

cell or phagocytic versus nonphagocytic 

target cell); and 

• EMP dimensions in relation to cell size (e.g., 

as a factor distinguishing total phagocytosis 

and partial frustrated phagocytosis).

Cell generation of ROS is seen generally in 

phagocytic uptake of elongate or nonelongate 

particles (e.g., as a respiratory burst). In normal phagocytosis, there is a maturation of the 

phagosomal membrane, with progression to a 

phagolysosomal structure for attempted lysosomal digestion. Anomalous behavior of this 

system may occur in frustrated phagocytosis 

of long EMPs. The hypothesis of frustrated 

phagocytosis suggests that EMPs that are too 

long to permit full invagination may stimulate 

cells to generate ROS or anomalously release 

lytic factors into the extracellular annulus rather than into a closed intracellular phagosome. 

EMP surfaces may be tested for direct membranolytic or cytotoxic activities that are dependent 

on surface composition or structure. As a guide, 

membranolytic or cytotoxic activities of nonelongate particulate silicates are dependent on 

surface properties. Nonelongate particulate silicates also provide an example of failure of in vitro cytotoxicity to relate with pathogenicity (e.g., 

respirable particles of quartz or kaolin clay significantly differ in disease risk for fibrosis, but 

are comparably cytotoxic in vitro unless they are 

preconditioned with pulmonary surfactants and 

then subjected to phagolysosomal digestion). In 

vitro studies of direct versus indirect induction 

of genotoxic activities may consider factors affecting the bioavailability of the nuclear genetic 

material (e.g., the state of phagocytic activity of 

the cell or the stages in the cell cycle with collapse of the nuclear membrane in mitosis). 

These again suggest care in the preparation of 

EMPs and the manner of challenge with EMPs 

employed in in vitro experiments.

The two modes of primary damage, a release 

of reactive toxic agents induced by long particulates or a surface-based membranolytic or 

genotoxic mechanism, may be involved singly 

or jointly in primary cell responses to EMPs. 

These may be investigated by comparing the 

effects of different types of EMPs (e.g., relative potencies of erionite fibers and amphibole 

asbestos fibers in in vitro cell transformation 

studies are different than their potencies in in 

vivo induction of mesothelioma). 
78 NIOSH CIB 62 • Asbestos

In the second phase of cellular response to EMPs, 

the central dogma of intracellular response is 

being intensively researched. The initial extracellular primary damage induces intracellular 

signaling (e.g., by MAPK), which causes a cascade of kinase activities that stimulate selective 

nuclear transcription of mRNAs, leading to 

production of TNF-α or other cytokines for extracellular signaling of target cells. Those other 

cytokines may induce cell proliferation toward 

cancer or collagen synthesis toward fibrosis. 

Further definition of signaling mechanisms and 

analyses of their induction by different primary 

EMP-cellular interactions may better define the 

ultimate role of EMP properties in the overall 

process. That research, again, may be facilitated 

by using different specific types of EMPs, each 

with relatively homogeneous morphology and 

surface properties. 

Although full investigation of biopersistence 

of EMPs may require long-term animal model 

studies, in vitro systems coupled with advanced 

surface analytical tools (e.g., field emission 

SEM–energy dispersive X-ray spectroscopy or 

scanning Auger spectroscopy) may help guide 

in vivo studies. This could be done by detailing 

specific surface properties of EMPs and their 

modifications under cell-free or in vitro conditions representing the local pH and reactive 

species at the EMP surface under conditions 

of extracellular, intra-phagolysosomal, or frustrated annular phagocytic environments. 

3.4.2 Conduct Animal Studies to 

Ascertain the Physical and 

Chemical Properties that 

Influence the Toxicity of 

Asbestos Fibers and Other EMPs

A multispecies testing approach has been recommended for short-term assays [ILSI 2005] 

and chronic inhalation studies [EPA 2000] 

that would provide solid scientific evidence 

on which to base human risk assessments for a 

variety of EMPs. To date, the most substantial 

base of human health data for estimating lung 

cancer risk is for workers exposed to fibers 

from different varieties of asbestos minerals.

There are similarities between animal species 

and humans in deposition, clearance, and retention of inhaled particles in the lungs. For 

example, peak alveolar deposition fraction is 

greatest for particles at an AED of about 2 μm in 

humans and about 1 μm for rodents. However, 

some interspecies differences have been identified. Variations in ventilation, airway anatomy, 

and airway cell morphology and distribution account for quantitative differences in deposition 

pattern and rate of clearance among species. In 

addition, the efficacy of pulmonary macrophage 

function differs among species. All these differences could affect particle clearance and retention. It has been suggested that the following 

species differences should be considered in the 

design of experimental animal inhalation studies of elongate particles [Dai and Yu 1988; Warheit et al. 1988; Warheit 1989].

• Due to differences in airway structure, 

airway size, and ventilation parameters, a 

greater fraction with large AED particles 

are deposited in humans than in rodents.

• Alveolar deposition fraction in humans 

varies with workload. An increase in the 

workload reduces the deposition fraction 

in the alveolar region because more of 

the inhaled particulate is deposited in the 

extra-thoracic and bronchial regions. 

• Mouth breathing by humans results in a 

greater upper bronchial deposition and 

enhanced particle penetration to the peripheral lung.
NIOSH CIB 62 • Asbestos 79

• For rats and hamsters, alveolar deposition 

becomes practically zero when particle 

AED exceeds 3.0 μm and aspect ratio exceeds 10. In contrast, considerable alveolar 

deposition is found for humans breathing 

at rest, even for EPs with AEDs approaching 5 μm and aspect ratio exceeding 10.

• Rodents have smaller-diameter airways 

than humans, a characteristic which increases the chance for particle deposition 

via contact with airway surfaces. 

• Turbulent air flow, which enhances particle 

deposition via impaction, is common in 

human airways but rare in rodent airways.

• Variations in airway branching patterns 

may account for significant differences 

in deposition between humans and rodents. Human airways are characterized 

by symmetrical branching, wherein each 

bifurcation is located near the centerline 

of the parent airway. This symmetry favors deposition “hotspots” on carinal 

ridges at the bifurcations due to disrupted 

airstreams and local turbulence. Rodent 

airways are characterized by asymmetric 

branching, which results in a more diffuse 

deposition pattern because the bulk flow 

of inspired air follows the major airways 

with little change in velocity or direction. 

• Alveolar clearance is slower in humans 

than in rats. Human dosimetry models 

predict that, at nonoverloading exposure 

concentrations, a greater proportion of 

particles deposited in the alveolar region 

will be interstitialized and sequestered in 

humans than in rats.

An important consideration in the conduct and 

interpretation of animal studies is the selection 

of well characterized (with respect to chemical and physical parameters) and appropriately 

sized EMPs that take into account differences 

in deposition and clearance characteristics 

between rodents and humans. EMPs that are 

capable of being deposited in the bronchoalveolar region of humans cannot be completely 

evaluated in animal inhalation studies because 

the maximum thoracic size for particles in rodents is approximately 2 μm AED, which is 

less than the maximum thoracic size of about 

3 μm AED for humans [Timbrell 1982; Su and 

Cheng 2005].

3.4.2.1 Short-Term Animal Studies

There are several advantages to conducting 

short-term animal studies in rats; one is that 

the information gained (e.g., regarding overload and maximum tolerated dose [MTD]) 

can be used to more effectively design chronic 

inhalation studies [ILSI 2005]. The objectives 

of these studies would be to

• Evaluate EMP deposition, translocation, 

and clearance mechanisms;

• Compare the biopersistence of EMPs retained in the lung with results from in vitro durability assays; 

• Compare in vivo pulmonary responses to 

in vitro bioactivity for EMPs of different 

dimensions; and 

• Compare cancer and noncancer toxicities 

for EMPs from asbestiform and nonasbestiform amphibole mineral varieties of 

varying shapes, as well as within narrow 

ranges of length and width. 

More fundamental studies should also be performed to

• Identify biomarkers or tracer/imaging 

methods that could be used to predict or 

monitor active pulmonary inflammation, 

pulmonary fibrosis, and malignant transformation; 
80 NIOSH CIB 62 • Asbestos

• Investigate mechanisms of EMP-induced 

pulmonary disease; and 

• Determine whether cell proliferation in 

the lungs (terminal bronchioles and alveolar ducts) can be a predictive measure of 

pathogenicity following brief inhalation exposure and use of the BrdU assay [Cullen et 

al. 1997].

Exposure protocols for tracheal inhalation or 

instillation in an animal model for short-term 

in vivo studies using field-collected or laboratory-generated EMPs should address possible 

adulteration of EMP morphology (e.g., anomalous agglomeration of particles). This might 

be addressed in part by preconditioning EMPs 

in a delivery vehicle containing representative 

components of pulmonary hypophase fluids. 

Exposure protocols using pharyngeal aspiration as a delivery system should be considered, 

given the observations in studies with singlewalled carbon nanotubes that such a delivery 

system closely mimics animal inhalation studies [Shvedova et al. 2005, 2008].

Studies evaluating the roles of biopersistence 

and dimension in the development of noncancer 

and cancer endpoints from exposure to EMPs 

are also needed. These studies should attempt to 

elucidate the physicochemical parameters that 

might affect bio-durability of EMPs of specific 

dimensions. Although short-term animal inhalation studies would be informative, companion 

in vitro assays should also be conducted to assess their validity for screening EMPs.

3.4.2.2 Long-Term Animal Studies

Chronic animal inhalation studies are required 

to address the impacts of dimension, morphology, chemistry, and biopersistence on critical 

disease endpoints of cancer induction and 

nonmalignant respiratory disease. The EPA’s 

proposed testing guidelines should be considered as the criteria for establishing the testing 

parameters for chronic studies [EPA 2001].

To date, chronic inhalation studies have been 

conducted with different animal species and different types of EPs. However, it remains uncertain which species of animal(s) best predict(s) 

the risk of respiratory disease(s) for workers 

exposed to different EPs. Chronic inhalation 

studies should be initiated to establish exposure/

dose-response relationships for at least two animal species. The rat has historically been the 

animal of choice for chronic inhalation studies 

with EPs, but the low incidence of lung tumors 

and mesotheliomas in rats exposed to asbestos 

fibers suggests that rats may be less sensitive than 

humans. Therefore, any future consideration for 

conducting long-term animal inhalation studies 

should address the need for using a multispecies 

testing approach to help provide solid scientific 

evidence on which to base human risk assessments for a variety of EMPs of different durabilities and dimensions. For example, some recent 

studies suggest that the hamster may be a more 

sensitive model for mesothelioma than the rat. 

Validation of appropriate animal models could 

reduce the resources needed to perform longterm experimental studies on other EMP types 

[EPA 2001].

Multidose animal inhalation studies with asbestos (probably a carefully selected and wellcharacterized chrysotile, because most of the 

estimates of human risk have been established 

from epidemiological studies of chrysotileexposed workers) are needed to provide an improved basis for comparing the potential cancer and noncancer risks associated with other 

types of EMPs and various types of synthetic 

EPs. The asbestos fibers administered in these 

animal studies should be comparable in dimension to those fibers found in the occupational 
NIOSH CIB 62 • Asbestos 81

environment. The results from these studies 

with asbestos (e.g., chrysotile) would provide 

a “gold standard” that could be used to validate 

the utility of long-term inhalation studies (in 

rats or other species) for predicting human risks 

of exposure to various types of EMPs.

3.4.3 Evaluate Toxicological 

Mechanisms to Develop 

Early Biomarkers of Human 

Health Effects

The following scheme using acellular and cellular tests can be conducted to develop a mechanistic understanding of fiber toxicity and to 

support the development of in vivo biomarkers of effect in humans. These studies must use 

well-characterized EMP samples as described 

in the tiered testing strategy presented in Section 3.4. The use of size-selected fractions of 

EMPs could provide information needed to 

understand the relationships between dimension and bioactivity. 

Acellular assays could include measurement of 

the generation of ROS employing electron spin 

resonance (ESR) or oxidant sensitive fluorescent 

dyes. Evaluation of the mobilization of metal ions 

from EMPs could indicate cytotoxic potential. 

The in vitro cellular tests could include the following: 

• generation of reactive species measured 

by ESR or fluorescent dyes;

• generation of inflammatory, fibrogenic, 

and proliferative mediators, such as TNFalpha, IL-1, and TGF;

• DNA damage by comet assay;

• effects on cell growth regulation by measuring cell proliferation;

• effects on mitosis and aneuploidy, determined by confocal fluorescent microscopy; and

• signal transduction pathways, such as 

MAPK, and phosphoinositide-3 (PI3) kinase pathways.

In vivo tests would measure markers of inflammation (e.g., BAL neutrophils, inflammatory 

cytokines and chemokines), fibrosis (collagen, hydroxyproline), and proliferation (BrdU 

assay, hyperplasia) that precede pathology. 

Knockout mice or pathway inhibitors in rats 

may be used to confirm mechanistic pathways 

identified in vitro and develop biomarkers for 

disease initiation and progression. Potential 

biomarkers identified in in vitro and in vivo

studies would be evaluated in human populations with known exposure to EMPs, and the 

type and extent of the relationships between 

the marker and clinical signs of disease could 

be determined.

3.5 Develop Information and 

Knowledge on Occupational 

Exposures to Asbestos 

Fibers and Other EMPs and 

Related Health Outcomes 

Many studies have been published concerning 

occupational exposures to asbestos fibers and associated health effects. These studies have formed 

a knowledge base that has supported increased 

regulation of occupational asbestos exposures 

and substantial reductions in asbestos use and 

asbestos exposures in the United States over the 

past several decades. But, as this Roadmap makes 

clear, much less is known about other types of 

mineral fibers and EMPs in terms of occupational exposures and potential health effects.
82 NIOSH CIB 62 • Asbestos

Research is needed to produce information on 

• current estimates and, where possible, future projections of numbers of U.S. workers exposed to asbestos fibers;

• levels of current exposures and nature of 

the exposures (e.g., continuous, short-term, 

or intermittent); and

• the nature of any concomitant dust exposures.

Similar research is needed to produce analogous information about occupational exposures to other EMPs. Research is needed to 

assess and quantify potential human health 

risks associated with occupational exposures 

to other EMPs, as well as to better understand 

and quantify the epidemiology of asbestosrelated diseases by using more refined indices 

of exposure. Research is also needed to produce improved methods and clinical guidance 

for screening, diagnosis, secondary prevention, 

and treatment of diseases caused by asbestos fibers and other hazardous EMPs.

3.5.1 Assess Available Information 

on Occupational Exposures to 

Asbestos Fibers and Other EMPs 

A fully informed strategy for prioritizing research on EMPs should be based on preliminary 

systematic collection and evaluation of available 

information on (1)  industries/occupations/job 

tasks/processes with exposure to various types 

of asbestos fibers and other EMPs; (2) numbers 

of workers exposed; (3) characteristics and levels of exposures; and (4) associated concomitant 

particulate exposures. Such information could 

enable estimations of 

• the overall distribution and levels of occupational exposures and an estimate of 

the total number of workers exposed to 

EMPs currently, in the past, and projected in the future; and

• the specific distributions and levels of exposures to each particular type of EMP, 

as well as numbers of workers exposed to 

each type of EMP currently, in the past, 

and projected in the future.

To complement readily available information 

disseminated by the USGS on annual domestic 

production and importation of raw asbestos, 

data on the annual amounts of asbestos imported into the United States in the form of any 

asbestos-containing products should be aggregated and made easily accessible.

Additional efforts should be made to collect, review, and summarize available occupational exposure information and to collect and analyze 

representative air samples relating to various 

types of EMPs. For example, systematic compilation of exposure data collected by OSHA, 

MSHA, NIOSH, state agencies, and private 

industry could contribute to an improved understanding of current occupational exposures 

to EMPs, particularly if there are opportunities 

to (re)analyze collected samples with use of enhanced analytical methods to better characterize the exposures (see Section 3.6). To help limit 

potential impact of sampling bias that may be 

inherent in the available EMP exposure data, 

these initial efforts should be supplemented 

with efforts to systematically identify, sample, 

and characterize EMP exposures throughout U.S. industry. These exposure assessments 

should include workplaces in which a fraction 

of the dust comprises EMPs (i.e., mixed-dust 

environments), and occupational environments 

in which EMPs may not meet the current regulatory criteria to be counted (i.e., “short” fibers). 

With appropriate planning and resources, such 

efforts could be designed and implemented as 

ongoing surveillance of occupational exposures 
NIOSH CIB 62 • Asbestos 83

to EMPs, with periodic summary reporting of 

findings. Representative EMP exposure data 

could help identify worker populations or particular types of EMPs warranting further study 

(i.e., more in-depth exposure assessment; medical surveillance; epidemiologic studies of particular types of EMPs, processes, job tasks, occupations, or industries; and toxicity studies of 

particular EMPs). Occupational exposure data 

should be collected and stored in a comprehensive database. Information similar to that 

described by Marchant et al. [2002] should be 

incorporated into the database to support these 

efforts. This could be accomplished in parallel 

with efforts to develop an occupational exposure 

database for nanotechnology [Miller et al. 2007] 

or efforts to develop a national occupational exposure database [Middendorf et al. 2007].

3.5.2 Collect and Analyze Available 

Information on Health 

Outcomes Associated with 

Exposures to Asbestos Fibers 

and Other EMPs

The body of knowledge concerning human 

health effects from exposure to EMPs consists 

primarily of findings from epidemiological 

studies of workers exposed to asbestos fibers. 

There is general agreement that workers exposed to fibers from any asbestiform amphibole mineral would be at risk of serious adverse health outcomes of the type caused by 

exposure to fibers from the six commercially 

exploited asbestos minerals. NIOSH commented on the most recently proposed MSHA 

rule on asbestos (subsequently promulgated as 

a final rule), stating that “NIOSH remains concerned that the regulatory definition of asbestos should include asbestiform mineral fibers 

such as winchite and richterite, which were 

of major importance as contaminants in the 

Libby, MT, vermiculite” [NIOSH 2005]. To ensure a clear science base that might support a 

formal recommendation for control of occupational exposures to all asbestiform amphibole 

fibers, it would be reasonable to thoroughly 

review, assess, and summarize the available 

information on asbestiform amphiboles such 

as winchite, richterite, and fluoro-edenite that 

have not been commercially exploited. 

It will also be important to quantitatively determine the health risks posed by EMPs from 

nonasbestiform amphiboles and to compare 

them to the risks posed by fibers from asbestiform amphiboles. If nonasbestiform amphibole 

EMPs are, in fact, associated with some risk, a 

quantitative risk assessment would be needed 

to understand the risks relative to those associated with exposures to asbestos fibers. If new 

epidemiological and other evidence is sufficient 

to support such a risk estimate, that could lead 

to the development of risk management policies 

for nonasbestiform amphibole EMPs distinct 

from risk management policies for asbestos fibers. Risk management policies that differ for 

asbestiform and nonasbestiform amphiboles 

would motivate the development and routine 

use of new analytical methods that differentiate 

asbestiform from nonasbestiform particles.

In addition to collecting and analyzing information on health outcomes associated with exposures to asbestiform EMPs and EMPs from 

nonasbestiform amphiboles, similar information 

related to other EMPs (e.g., erionite, wollastonite, 

attapulgite, and fibrous talc) should be collected 

for systematic analysis. Additional relevant information may be gleaned from epidemiological 

studies conducted on some SVFs (e.g., glass and 

mineral wool fibers, ceramic fibers). 

Surveillance and epidemiological studies generally have been circumscribed by the long latency 
84 NIOSH CIB 62 • Asbestos

periods that characterize manifestations of either 

pulmonary fibrosis (e.g., as detected by chest radiography or pulmonary function tests) or cancer caused by asbestos exposures. Modern medical pulmonary imaging techniques or bioassays 

of circulating levels of cytokines or other biochemical factors associated with disease processes might be adaptable to better define early stages 

of asbestosis, and might provide a new paradigm 

for early detection of the active disease process. 

For example, positron emission tomographic imaging with use of tracers indicative of active collagen synthesis can detect fibrogenic response in 

a matter of weeks after quartz dust challenge in a 

rabbit animal model [Jones et al. 1997; Wallace et 

al. 2002].

3.5.3 Conduct Selective 

Epidemiological Studies of 

Workers Exposed to Asbestos 

Fibers and Other EMPs

Statistically powerful and well designed epidemiological studies are typically very expensive and time consuming, but they have been 

invaluable for defining associations between 

human health outcomes and occupational exposures. In fact, the strongest human evidence 

indicating that, at a sufficient dose and with 

a sufficient latency, certain EMPs of thoracic 

dimension and high durability pose risks for 

malignant and nonmalignant respiratory disease has come from epidemiological studies of 

workers exposed to asbestos fibers. 

Outcomes from proposed research efforts 

outlined above in Section 3.5.2 may identify 

additional opportunities for informative epidemiological studies following the example 

of NIOSH researchers who have recently undertaken a reanalysis of data from a prior epidemiological study of asbestos textile workers, 

after having more thoroughly characterized 

exposures with use of sample filters archived 

from that study [Kuempel et al. 2006]. Outcomes from the approaches outlined above in 

Section 3.3.2 might also potentially identify 

opportunities for aggregate meta-analyses of 

data from multiple prior epidemiological studies, allowing an assessment of risks across various types of EMPs. Recently published research 

illustrates the potential of such meta-analyses 

to contribute to an understanding of determinants of disease caused by exposure to asbestos 

and related EMPs [Berman et al. 1995; Berman 

and Crump 2008b; Berman 2010].

Given the ongoing and widespread occupational and environmental exposure to Libby 

vermiculite, a more complete understanding of 

the mortality experience of the Libby occupational cohort could shed light on risks associated with exposure to the Libby amphibole, 

such as exposures at the World Trade Center 

disaster, as well as the health effects among the 

Libby community. Analyses of the Libby worker cohort continue and future analyses are envisioned, with the following aims: 

• complete exposure-response modeling and 

occupational risk assessment for mesothelioma and asbestosis, and

• description of nonrespiratory outcomes 

(e.g., mortality with rheumatoid arthritis and mortality from extrapulmonary 

cancers).

Other research relating to Libby amphibole 

also continues. EPA and ATSDR have been engaged in a program of research involving several recent projects, including evaluation of

• the relationship between radiographic abnormalities and lung function in Libby 

community residents, finding that diffuse 

pleural thickening on radiography was a 
NIOSH CIB 62 • Asbestos 85

significant predictor of both restrictive and 

obstructive patterns on spirometry. 

• the natural history of radiographic disease progression, observing an exposureresponse relationship between cumulative 

fiber exposure and small opacity profusion level on chest radiographs of Libby 

workers.

• the effect of exposure to asbestos-containing 

Libby vermiculite at 28 processing sites in 

the United States. Activities included conducting medical screening of former workers and household contacts at six sites; a 

summary report is available at www.atsdr.

cdc.gov/asbestos/sites/national_map.

• cases of mesothelioma, asbestosis, and 

lung cancer among former workers and 

others with nonoccupational exposure 

associated with a vermiculite processing 

facility in northeast Minneapolis. 

• disease progression in workers exposed 

to asbestos-containing vermiculite ore at 

a fertilizer plant in Marysville, Ohio. 

• autoimmune conditions not classically 

associated with asbestos exposure and 

health effects associated with low-level 

exposure and childhood exposure. 

In addition, ATSDR continues to update its 

Tremolite Asbestos Registry (TAR) of individuals exposed to vermiculite-associated asbestiform amphibole in Libby. Opportunities for 

additional informative epidemiological studies 

relating to Libby amphibole could be pursued 

in the future, particularly if an EM-based jobexposure matrix for workers exposed to the 

Libby amphiboles is developed, or if amphibole exposures during commercial building 

and household construction renovation tasks 

were well-characterized. 

Large unstudied populations with sufficiently 

high exposure to commercial asbestos fibers 

are unlikely to be identified in developed countries such as the United States, where asbestos 

use has been markedly curtailed and where occupational exposures have been strictly regulated in recent decades. Nevertheless, some 

developing countries (where asbestos use continues on a large scale and where exposures 

may be less regulated) may offer opportunities 

for de novo epidemiological studies that could 

contribute to a more refined understanding 

of the association of human health outcomes 

with occupational exposures to asbestos fibers 

and other EMPs. 

Opportunities for epidemiological studies of exposed workers might be sought in other countries where medical registry data and historical 

or current workplace sampling data are available 

(e.g., in China, where epidemiological studies 

of another occupational dust disease, silicosis, 

have been collaboratively conducted by Chinese 

and NIOSH researchers [Chen et al. 2005]). 

Opportunities may also exist in other countries for epidemiological studies of nonworker 

populations exposed to asbestos in ways not 

encountered in more developed countries. For 

example, regular whitewashing of the interiors 

of homes has, in more than one country, been 

shown to be fraught with hazard. In parts of 

Greece and Turkey and in New Caledonia, the 

local earthen material traditionally used for 

whitewashing homes was predominantly composed of tremolite asbestos, resulting in high 

rates of nonmalignant pleural plaques [Constantopoulos et al. 1987], lung cancer [Luce et 

al 2000; Menvielle et al. 2003], and malignant 

mesothelioma [Sakellariou et al. 1996; Senyiğit 

et al. 2000]. The whitewashing work, including 

crushing of the dry material before addition of 

water, was typically done by women with small 
86 NIOSH CIB 62 • Asbestos

children in tow, placing both sexes at risk of 

intermittent heavy exposures very early in life 

[Sakellariou et al. 1996]. This, along with the 

longer-term and lower-level exposures associated with inhabiting homes whitewashed with 

this asbestos-containing material, represents 

an exposure pattern very different from the occupational exposures to asbestos studied in the 

Unites States and other industrialized countries. 

Results of epidemiological studies of workers 

exposed to EMPs, such as from nonasbestiform amphibole minerals or minerals in talc 

deposits, have provided limited evidence of 

an association between occupational exposure 

and lung cancer or mesothelioma. It will be 

important to establish a priori criteria to enable results of epidemiological studies or metaanalyses to be used to indicate whether or not 

occupational exposure to EMPs from nonasbestiform amphibole minerals or minerals in 

talc deposits is associated with a risk level that 

warrants preventive intervention. Clearly laying out these criteria and assessing the feasibility of conducting necessary studies should 

be done by a panel of knowledgeable experts. 

Laboratory research will undoubtedly shed 

much light on the issue of potential human 

health risks associated with specific physicochemical characteristics of EMPs. Still, where 

such studies are not only feasible but also likely 

informative, there is reason to consider further 

epidemiological studies of worker populations 

exposed to EMPs from nonasbestiform amphiboles. These may be conducted either de novo

or through updating of prior studies for more 

complete follow-up of health outcomes and/or 

through reanalyzing archived exposure samples for development of more specific knowledge concerning etiologic determinants and 

quantitative risk.

Other studies worthy of consideration include 

these:

• Epidemiological studies of worker populations incidentally exposed to EMPs 

from fibrous minerals, including asbestiform minerals (e.g., those associated with 

Libby vermiculite);

• Epidemiological studies of populations exposed to other less-well-studied EMPs (e.g., 

wollastonite, attapulgite, and erionite); and 

• Meta-analyses of data from multiple epidemiological studies of various worker 

populations, each exposed to EMPs with 

somewhat different attributes (such as 

EMP type or dimensions), to better define 

specific determinants of EMP-associated 

adverse health outcomes for purposes of 

risk assessment. 

The following criteria should be considered in 

selecting and prioritizing possible populations 

for epidemiological study: (1) type of EMP exposure (e.g., mineral source, chemical composition, crystalline structure, surface characteristics, and durability); (2)  adequate exposure 

information (e.g., EMP concentrations and 

[bivariate] EMP dimensions); (3)  good work 

histories; (4) sufficient latency; (5) number of 

workers needed to provide adequate statistical power for the health outcome(s) of interest; 

and (6) availability of data on other potentially 

confounding risk factors. Priority should be 

placed on epidemiological studies with potential to contribute to the understanding of EMP 

characteristics that determine toxicity, including type of mineral source (e.g., asbestiform 

mineral habit vs. other fibrous mineral habit 

vs. blocky mineral habit) and morphology and 

other aspects of the airborne EMPs (e.g., dimensions [length and width], chemical composition, crystalline structure, surface characteristics, and durability).
NIOSH CIB 62 • Asbestos 87

In addition to epidemiological studies that 

address etiology and that quantify exposurerelated risk, epidemiological studies can be 

used to better understand the pathogenesis of 

lung diseases caused by asbestos fibers and other EMPs. For example, appropriately designed 

or reconstructed epidemiological studies could 

be used to assess the relationship between the 

physicochemical properties of EMPs, lung fibrosis, and lung cancer. 

3.5.4 Improve Clinical Tools and 

Practices for Screening, 

Diagnosis, Treatment, and 

Secondary Prevention of 

Diseases Caused by Asbestos 

Fibers and Other EMPs

Given the huge human and economic impact of 

asbestos-related disease and litigation, Congress 

has considered asbestos-related legislation on 

several occasions in recent years. To date, bills 

with provisions to require private industry to 

fund an asbestos victims’ trust fund have not 

succeeded in Congress. Most recently, the Ban 

Asbestos in America Act, which was passed by 

the U.S. Senate in 2007 but was not acted on 

in the House of Representatives, would have 

authorized and funded a network of asbestosrelated disease research and treatment centers 

to conduct studies, including clinical trials, on 

effective treatment, early detection, and prevention [U.S. Senate 2007]. This bill also called for 

the establishment of a mechanism for coordinating and providing data and specimens relating to asbestos-caused diseases from cancer 

registries and other centers, including a recently 

funded virtual biospecimen bank for mesothelioma [Mesothelioma Virtual Bank 2007]. 

Various research objectives relevant to clinical 

aspects of asbestos-related diseases are worthy 

of pursuit by NIOSH and other federal agencies, along with their partners, to improve 

screening, diagnosis, secondary prevention, and 

treatment. These include but are not limited to 

the following objectives: 

• Continue to develop and validate technical standards for the assessment of digital 

chest radiographs with the ILO classification system. The ILO system for classifying 

chest radiographs of the pneumoconioses 

is widely used as a standard throughout the 

world. Although initially intended for use 

in epidemiological studies, the ILO system 

is now also commonly used as a basis for 

describing severity of disease in clinical 

care and for awarding compensation to 

individuals affected by nonmalignant diseases of the chest caused by asbestos and 

other airborne dusts. To ensure that digital 

chest radiographic methods used in future 

clinical and epidemiological studies can 

be compared with past studies based on 

conventional film radiography, there is a 

critical need to continue ongoing research 

to validate use of the ILO system for classification of digital chest images.

• Develop and promote standardized assessment of nonmalignant dust-induced 

diseases, including asbestos-related pleural and parenchymal disease, on computed tomography (CT) images of the chest. 

Over the past several decades, CT scanning of the chest has been increasingly 

used for assessing chest disease, and highresolution CT scanning is often done in 

clinical settings. Although approaches for 

standardizing classifications of CT images for dust-related diseases have been 

proposed, none have yet been widely adopted or authoritatively promoted. 
88 NIOSH CIB 62 • Asbestos

• Develop, validate, and promote standardization of approaches for assessment of 

past asbestos exposures by measurement 

of asbestos bodies and uncoated fibers, 

particularly in samples collected noninvasively (e.g., sputum). Various approaches 

for quantifying fiber burden have been 

used for research and clinical purposes, but 

results are often difficult or impossible to 

compare across different studies because of 

lack of standardization and the differential 

rates of biopersistence and translocation of 

various types of asbestos fibers. 

• Develop and validate biomarkers for asbestosis, lung cancer, and mesothelioma 

to enable more specific identification of 

those at risk or early detection of disease 

in those previously exposed to asbestos. 

For example, noninvasive bioassays for 

mesothelioma warrant further research 

before they can be considered ready for 

routine application in clinical practice. 

• Develop and/or adapt emerging medical imaging techniques to better define 

stages of asbestosis, or to provide a new 

paradigm for early detection or grading 

of the active disease process. For example, 

positron emission tomographic (PET) 

imaging using tracers indicative of active 

collagen synthesis can detect pulmonary 

fibrogenic response in a matter of weeks 

after quartz dust challenge in a rabbit animal model [Jones et al. 1997; Wallace et al. 

2002]. This holds promise for noninvasive 

approaches for earlier clinical detection 

and more sensitive surveillance and epidemiological studies, that to date have been 

circumscribed by the long latency periods 

that characterize pulmonary fibrosis associated with asbestos exposure (e.g., as detected by conventional chest radiography).

• Develop new treatment options to reduce 

risk of malignant and nonmalignant disease 

among those exposed to asbestos and to effectively treat established asbestos-induced 

disease. For example, many widely used 

anti-inflammatory drugs exert their effect 

by inhibiting cyclooxygenase-2 (COX-2), 

an enzyme that is induced in inflammatory 

and malignant (including premalignant) 

processes. Promising results of laboratory 

and case-control epidemiological studies 

have led to clinical trials of COX-2 inhibitors as adjuvant therapy to enhance treatments for various types of cancer. Research 

is warranted to determine whether these 

drugs can reduce the risk of asbestos-related malignancies in exposed individuals. 

• Authoritatively and regularly update and 

disseminate clear clinical guidance for 

practitioners, based on expert synthesis 

of the available literature.

3.6 Develop Improved 

Sampling and Analytical 

Methods for Asbestos 

Fibers and Other EMPs

There are important scientific gaps in understanding the health impacts of exposure to 

EMPs. Changes in how EMPs are defined for 

regulatory purposes will likely have to be accompanied by improvements to currently used 

analytical methods or development and application of new analytical methods. An ability to 

differentiate between fibers from the asbestos 

minerals and EMPs from their nonasbestiform 

analogs in air samples is an important need, especially for mineral-specific recommendations 

(e.g., occupational exposure limits). However, 

overcoming this obstacle may be difficult because of (1) the lack of standard criteria for the 
NIOSH CIB 62 • Asbestos 89

mineralogical identification of airborne EMPs 

and (2) technical difficulties in generating test 

aerosols of size-specific EMPs representative of 

worker exposures so that sampling and analytical methods can be tested and validated.

Improvements in exposure assessment methods are needed to increase the accuracy of the 

methods used to identify, differentiate, and count 

EMPs captured in air-sampling filter media. Until new analytical methods are developed and 

validated, it will be necessary to investigate the 

various proposals that have been made to modify 

current analytical methods, such as those discussed in Section 3.6.2, and additional modifications to the current analytical methods. 

Manual microscopy methods are labor-intensive 

and error-prone. Automated analyses would 

permit examination of larger sample fractions 

and improve the accuracy of particle classification. Developing a practical method that accurately counts and sizes all EMPs could improve 

risk assessments and exposure assessments done 

in support of risk management. Automated 

methods could reduce operator bias and interlaboratory variability, providing more consistent results for risk assessments.

Some barriers to improving current analytical 

methods have been identified. Increasing the 

optical resolution of PCM analysis may help 

to increase counts of thinner asbestos fibers. 

However, any increases in optical microscopy 

resolution will not be sufficient to detect all asbestos fibers. In addition, any improvements in 

counting EMPs (e.g., an increase in the number 

of EMPs observed and counted) will need to 

be evaluated by comparing them with counts 

made by the current PCM method. The use of 

electron microscopy (EM) would improve the 

capability to detect thin fibers and also provide 

a means to identify many types of minerals.

However, the routine use of EM would

• require the development of standardized 

analytical criteria for the identification of 

various EMPs; 

• require specialized experience in microscopy and mineral identification; 

• increase analytical costs; and 

• potentially increase the lag time between 

collecting the sample and obtaining results. 

In some workplace situations, such as in construction, increases in the time needed to analyze samples and identify EMPs could potentially delay the implementation of appropriate 

control measures to reduce exposures.

Several potential sampling and analytical improvements are currently under study. Some 

of the studies are aimed at improving the accuracy of current techniques used for monitoring exposures to asbestos. One such study 

is evaluating the use of thoracic samplers for 

the collection of airborne EPs, and another 

concerns the use of gridded coverslips for 

PCM analyses. The proposed use of gridded 

coverslips for sample evaluation can aid in the 

counting of asbestos and other EMPs and can 

provide a means for “recounting” fibers at specific locations on a filter sample. Another study 

is evaluating the proposed ASTM method to 

determine whether interoperator variability of 

differential counting (to distinguish fibers of 

asbestos minerals from other EMPs) is within 

an acceptable range. 

Research to develop new methods is warranted. 

One such research area could be development 

of methods that would permit assessment of 

the potential biopersistence (e.g., durability) of 

EMPs collected on air sampling filters prior to 

their evaluation by PCM or other microscopic 

methods. If durability is deemed biologically 
90 NIOSH CIB 62 • Asbestos

relevant, then an exposure assessment limited 

to the durable EMPs collected on a sample 

would help to reduce possible analytical interferences caused by other, nondurable EMPs 

and may eliminate the need for mineral identification. Another such area would be improvement in EM particle identification techniques, 

such as field emission SEM and the capability to determine the elemental composition 

of EMPs with an SEM equipped with EDS. A 

third research area, largely conceptual at this 

time, would be development of techniques to 

more accurately reflect internal dose by quantifying or estimating the number of particles 

likely to be produced by splitting of asbestosfiber bundles deposited in the lung.

Modifications of current analytical methods 

and development of new analytical methods 

will require an assessment of their implications for worker health protection (e.g., how 

do the results using improved or new methods 

relate to human risk estimates based on counts 

of EMPs made by PCM?). To ensure that relevant toxicological parameters (e.g., dose, dimension, durability, and physicochemical parameters) are incorporated in the analysis and 

measurement, any changes in analytical methods should be made in concert with changes in 

how asbestos fibers or other EMPs are defined. 

3.6.1 Reduce Interoperator and 

Interlaboratory Variability of 

the Current Analytical Methods 

Used for Asbestos Fibers 

To ensure the validity of EMP counts on air 

samples, it is important to ensure consistency 

in EMP counts between and among analysts. 

Microscopy counts of EMPs on air sample filters are based on only a small percentage of 

the surface area of the filters, and the counting 

procedures require the analyst to make decisions on whether each observed particle meets 

specified criteria for counting. Interlaboratory 

sample exchange programs have been shown to 

be important for ensuring agreement in asbestos fiber counts between laboratories [Crawford 

et al. 1982]. Unfortunately, microscopists from 

different laboratories are unlikely to view exactly the same fields, and this alone accounts for 

some of the observed variation in fiber counts 

between microscopists. A mechanism to allow 

recounts of fibers from the exact same field areas would remove this variable and allow a better assessment of the variation attributable to 

microscopists in analyzing samples. 

A technique is under development for improving the accuracy of PCM-based fiber-counting 

by allowing the same sample fields to be examined by multiple microscopists or by the 

same microscopist on different occasions [Pang 

et al. 1984, 1989; Pang 2000]. The method involves the deposition of an almost transparent 

TEM grid onto the sample. Included with the 

grid are coordinates that allow relocation of 

each grid opening. Photomicrographs of typical 

grid openings superimposed on chrysotile and 

amosite samples have been published [Pang et 

al. 1989]. Slides prepared in this manner have 

been used in a Canadian proficiency test program for many years. The main errors affecting 

the counts of various types of fibers (e.g., chrysotile, amosite, and SVF) have been evaluated 

by examining large numbers of slides by large 

numbers of participants in this program. A recently developed scoring system for evaluating 

the performance of microscopists is based on 

errors compared with a reference value defined 

for each slide by the laboratory in which they 

were produced [Pang 2002]. A statistical analysis of the intragroup precision in this study was 

able to identify those analysts who were outliers 

[Harper and Bartolucci 2003]. In a pilot study, 
NIOSH CIB 62 • Asbestos 91

the pooled relative standard deviations, without 

the outliers, met the requirements for an unbiased air-sampling method. Further study is 

needed to validate these findings and to identify 

other techniques that can reduce interlaboratory and interoperator variability in counting 

asbestos fibers and other EMPs by PCM. 

Reference slides made from proficiency test 

filters from the American Industrial Hygiene 

Association (AIHA) have been created and circulated to laboratories and individual microscopists recruited from AIHA laboratory quality programs [Pang and Harper 2008; Harper 

et al. 2009]. The results illustrate an improved 

discrimination of fiber counts when the proficiency test materials have a more controlled 

composition. These reference slides have also 

been evaluated in Japan, the United Kingdom, 

and elsewhere in Europe. Further research will 

be useful in determining the value of these 

slides for training purposes.

3.6.2 Develop Analytical Methods 

with Improved Sensitivity 

to Visualize Thinner EMPs 

to Ensure a More Complete 

Evaluation of Airborne 

Exposures

Most PCMs can visualize EMPs with widths 

>0.25 μm, which is the approximate lower 

resolution limit when the microscope is operated at a magnification of 400× and calibrated 

to NIOSH 7400 specifications [NIOSH 1994a]. 

However, higher-end optical microscopes can 

resolve thinner widths, and, for crocidolite, 

they may resolve widths as thin as 0.1 μm.

Improvement in the optical resolution may be 

possible with use of an oil-immersion 100× objective with a numerical aperture of 1.49. Also, 

the use of 15× eyepiece oculars would help improve the visibility of small particles and thin 

EMPs in samples. However, using oil immersion has several drawbacks. When exposed to 

air for more than a few hours, the oil on the 

slide dries and its optical properties change. 

Also, the oil cannot be wiped off because the 

cover slip is likely to be moved and thus ruin 

the sample. For these reasons, using oil immersion does not permit recounts or further analysis for quality control purposes and is not an 

attractive alternative.

Other methods may also allow for increased 

resolution with optical microscopes. Anecdotal 

information on the use of PCM with darkmedium (DM) objectives, presented at a meeting in November 2007, suggests that analysts 

using DM objectives could resolve more blocks 

of the Health and Safety Executive/National 

Physical Laboratory (HSL/ULO) test slide‡‡

than are allowable for the method and produced higher counts of chrysotile fibers than 

expected [Harper et al. 2009]. The implication 

is that using DM objectives can resolve thinner 

chrysotile fibers than the accepted method. This 

methodology should be explored further to determine its resolution and potential application 

in asbestos exposure assessment.

As stated previously, because risk estimates for 

workers exposed to asbestos fibers have been 

‡‡ The HSE/NPL Mark II or HSL/ULO Mark III Phase 

Shift Test Slide checks or standardizes the visual detection limits of the PCM. The HSL/ULO Test Slide 

consists of a conventional glass microscope slide with 

seven sets of parallel line pairs of decreasing widths. 

The microscope must be able to resolve the blocks of 

lines in accordance with the certificate accompanying 

the slide. Only slides where at least one block of lines is 

intended to be invisible should be used. Microscopes 

that resolve fewer or greater numbers of blocks than 

stated on the certificate cannot be used in NIOSH 

Method 7400.
92 NIOSH CIB 62 • Asbestos

based on counts made by the current PCM 

method, counts made with improved optical 

microscope resolution capabilities would not 

be directly comparable to current occupational 

exposure limits for airborne asbestos fibers. 

Additionally, the findings that asbestos fibers 

thinner than 0.1 μm are most associated with 

mesothelioma and that optical microscopes 

cannot resolve fibers <0.1 μm in width suggest 

that alternatives to PCM should be researched.

TEM can resolve asbestos fibers with widths 

less than ~0.01 μm, which effectively detects the 

presence of all asbestos fibers and other EMPs 

collected on airborne samples. Both TEM and 

SEM provide greater resolution for detecting 

and sizing EMPs. Both methods also provide 

capability for mineral identification (TEM using selected area X-ray diffraction [SAED], and 

TEM and SEM using EDS or WDS for elemental analysis). The cost of using TEM and/or SEM 

for routine analysis of all samples would be considerably higher than PCM analysis and the 

turnaround time for analysis would be substantially longer. In addition, any routine use of EM 

methods for counting and sizing asbestos fibers 

or other EMPs would require formal evaluation 

of interoperator and interlaboratory variability. 

SEM is now a generally available method that 

can routinely resolve features down to ~0.05 

μm, an order of magnitude better than optical 

microscopes. Field emission SEM is now commercially available and further increases this 

resolution. In vitro or short-term or long-term 

animal model studies can now utilize these EM 

imaging technologies to characterize EMPs 

for studies of etiology and disease mechanism. 

EM analyses of EMP size and composition can 

be supplemented with analysis of surface elemental composition by scanning Auger spectroscopy or X-ray photoelectron spectroscopy. 

Investigation is needed to determine whether 

SEM-backscatter electron diffraction analysis 

can be adapted to EMP crystallographic analyses equivalent to TEM-SAED capability. The 

ease of sample preparation and data collection 

for SEM analysis in comparison with TEM analysis, along with an SEM advantage in visualizing 

EMP and EMP morphology (e.g., surface characteristics), provides reason to reevaluate SEM 

methods for EMP characterization and mineral 

identification for field and laboratory sample 

analysis.

3.6.3 Develop a Practical Analytical 

Method for Air Samples to 

Differentiate Asbestiform 

Fibers from the Asbestos 

Minerals and EMPs from Their 

Nonasbestiform Analogs 

A recently published ASTM method for distinguishing other EMPs from probable asbestos fibers uses PCM-determined morphologic features to differentiate asbestos fibers 

from other EMPs [ASTM 2006]. The proposed 

method has several points of deviation from 

existing PCM methods. It uses a new graticule that has not been tested for conformance 

with the traditional graticule used in standard 

PCM analysis of asbestos air samples. It specifies additional counting rules to classify particles, and there are few data to show these 

rules provide consistently achievable or meaningful results. Also, only limited data are available to show interoperator, intraoperator, or 

interlaboratory variation. These issues must be 

addressed before the method can be considered acceptable. NIOSH researchers are currently addressing these issues. Specific aims of 

the project are

• to determine the effect of using the traditional Walton-Beckett graticule and the 
NIOSH CIB 62 • Asbestos 93

new RIB graticule on the precision of measuring fiber dimensions; and

• to determine the interlaboratory variation 

of the proposed method for determining 

particle identities by observing morphological features of individual particles.

Anticipated outcomes of these ongoing research projects include a measure of method 

precision, which will help to determine whether the method meets the requirements of regulatory and other agencies. 

Although EM may currently not be suitable for 

routine analysis of samples of airborne EMPs, 

EM techniques used to characterize and identify minerals (e.g., differentiating between asbestos fibers and other EMPs) should be further investigated and evaluated to determine 

whether results are reproducible by multiple 

microscopists and laboratories.

3.6.4 Develop Analytical Methods to 

Assess Durability of EMPs

Although research has been conducted to determine the ability of biological assays to evaluate 

the biopersistence of EMPs in the lung, there is 

a need to consider how the assessment of EMP 

durability might be incorporated into the evaluation of air samples containing a heterogeneous 

mix of EMPs. Research with several types of 

glass fibers and some other SVFs indicate that 

they dissolve in media at different rates depending on the pH and that they dissolve more 

rapidly than chrysotile and amphibole asbestos fibers [Leineweber 1984]. Chrysotile fibers 

have been shown to dissolve at a rate that varies 

not only with the strength of the acid, but also 

with the type of acid. Amphibole asbestos fibers 

have been shown to be more resistant to dissolution than chrysotile fibers. Research suggests 

that the rate of dissolution in the lungs for most 

EMPs appears to be strongly dependent on their 

chemical composition, surface characteristics, 

and dimension. 

The selective dissolution of EMPs might be a 

useful approach for eliminating specific types 

of EMPs or other particles collected on air samples prior to analysis (e.g., microscopic counting). The removal of interfering EMPs prior to 

counting could potentially eliminate the need 

for additional analysis to identify EMPs on the 

sample. Selective dissolution of samples to remove interferences is well established in NIOSH 

practice for other analytes. NIOSH Method 5040 

for diesel exhaust has an option for using acidification of the filter sample with hydrochloric 

acid to remove carbonate interference [NIOSH 

2003a]. Silicate interferences for quartz by infrared spectroscopic detection are removed by 

phosphoric acid digestion in NIOSH Method 

7603 [NIOSH 2003b]. Although selective dissolution might be accomplished for some EMPs, 

research will be necessary to develop and characterize a procedure that would correlate residual EMP counts to the results of toxicity studies.

3.6.5 Develop and Validate Sizeselective Sampling Methods 

for EMPs

For measuring airborne concentrations of nonelongate particles in the workplace, conventions 

have been developed for sampling the aerosol 

fractions that penetrate to certain regions of the 

respiratory tract upon inhalation: the inhalable 

fraction of particulate that enters into the nose 

or the mouth; the thoracic fraction that penetrates into the thorax (i.e., beyond the larynx); 

and the respirable fraction that reaches the alveoli of the lung. The thoracic convention is recognized by NIOSH and other organizations that 

recommend exposure limits, and NIOSH has 
94 NIOSH CIB 62 • Asbestos

established precedence in applying it in RELs 

(e.g., the REL for metalworking fluid aerosols 

[NIOSH 1998]).

Asbestos fibers currently are collected for measurement by standard sampling and analytical 

methods (e.g., NIOSH Method 7400 [NIOSH 

1994a], in OSHA ID–160 [OSHA 1998], in 

Methods for the Determination of Hazardous 

Substances (MDHS) 39/4 [HSE 1995], and in 

ISO 8672 [ISO 1993]). In these methods, air 

samples are taken by means of a membrane filter housed in a cassette with a cowled sampling 

head. Early studies [Walton 1954] showed that 

the vertical cowl excludes some very coarse 

particles because of elutriation, but its selection 

characteristics should have little effect on the 

collection efficiency for asbestos fibers. However, when Chen and Baron [1996] evaluated the 

sampling cassette with a conductive cowl used 

in sampling for asbestos fibers, they found inlet deposition was higher in field measurements 

than predicted by models.

Unlike the WHO [1997], NIOSH has not recommended an upper limit for width of asbestos 

fibers to be counted because airborne asbestos 

fibers typically have widths <3 μm. The absence 

of an upper width criterion for the NIOSH 

Method 7400 A rules has generated criticism 

that some EMPs counted by this method may 

not be of thoracic size. Others have recommended NIOSH Method 7400 B rules for the 

sampling and analysis of various types of fibers 

and EPs, including asbestos fibers [Baron 1996], 

because the B rules specify an upper limit of 

3 μm for EP width. However, Method 7400 B 

rules have not been field-tested for occupational 

exposures to asbestos and many types of EPs.

Two separate but complementary investigations 

have examined the performance of thoracic samplers for EMPs [Jones et al. 2005; Maynard 2002]. 

Thoracic samplers allow the collection of airborne particles that meet the aerodynamic definition of thoracic-size EMPs (i.e., with physical 

widths equal to or less than 3 μm for the typical 

length distributions of fibers of silicate composition), collecting only those EMPs considered 

most pathogenic. The results of studies have indicated that penetration of some thoracic samplers is independent of EMP length, at least up to 

60 μm, indicating that the samplers’ penetration 

characteristics for an EP aerosol should be no different than that of an isometric aerosol. In a study 

be Jones et al. [2005], the relative ability of the 

thoracic samplers to produce adequately uniform 

distributions of EPs on the surface of the membrane filter was also tested. On the basis of results 

of these studies, two samplers appeared to meet 

the criteria of minimal selection bias with respect 

to EP length and uniform distribution on the collection filters. However, neither of these samplers 

has been tested under conditions of field use. 

NIOSH is currently evaluating these two thoracic 

samplers and the traditional cowled sampler in 

three different mining environments. The results 

from these studies have been published [Lee et al. 

2008; Lee et al. 2010], and each of the samplers 

gave fiber concentrations in proportion to their 

fiber loading rates, which is consistent with previous reports [Cherrie et al. 1986]. Thus, alternative samplers cannot be recommended until the 

impact of this effect on the established risk analysis has been evaluated.

3.7 From Research to 

Improved Public Health 

Policies for Asbestos Fibers 

and Other EMPs 

Section 3 of this Roadmap proposes several 

strategic goals and associated objectives for a 

multidisciplinary research program on asbestos 
NIOSH CIB 62 • Asbestos 95

fibers and other EMPs. In summary, accomplishing these goals is intended to (1)  further 

elucidate the physicochemical properties that 

contribute to their pathogenicity; (2)  improve 

existing analytical tools and develop new analytical tools for identifying and measuring exposures to EMPs with use of metrics that reflect 

the important determinants of toxicity (e.g., 

dimension and composition); (3) better define 

the nature and extent of occupational exposures to EMPs and their relationships to EMPrelated health outcomes among exposed worker 

populations; and (4) improve clinical tools for 

screening, diagnosis, secondary prevention, and 

treatment of EMP-related diseases. 

Results of much of the research to date (e.g., 

animal and human studies with asbestos and 

other EMPs) are readily available and should 

be considered in developing the research program, including the specification of minerals 

to be studied. Much of this evidence supports 

the important role of particle dimension as a 

determinant of lung deposition and retention 

and the concomitant role of particle composition and crystalline structure as a determinant 

of durability and biopersistence. Despite this 

body of research, several fundamental issues 

are not clearly understood, and a broad systematic approach to further toxicological and 

epidemiological research would help to reduce 

remaining uncertainties. Although long, thin 

asbestos fibers clearly cause respiratory disease, the role of unregulated short (i.e., <5 μm) 

asbestos fibers is not entirely clear. It also remains unclear to what extent each of the various physicochemical parameters of asbestos 

fibers is responsible for respiratory disease outcomes (e.g., asbestosis, lung cancer, and mesothelioma) observed in asbestos-exposed individuals. Limited evidence from studies with 

other EMPs confirms the importance of particle dimension and biopersistence in causing 

a biological response. However, uncertainty 

remains as to whether the respiratory disease 

outcomes for workers exposed to asbestos fibers can be anticipated for workers exposed to 

other EMPs of thoracic size and with elemental 

compositions similar to asbestos. 

Another important effort that can inform development of the research program will involve a 

systematic collection and review of available information on (1) industries and occupations with 

exposure to EMPs; (2) airborne exposure in these 

industries and occupations; and (3) numbers of 

workers potentially exposed in these industries 

and occupations. Additional relevant minerals 

and mineral habits identified should also be considered for study. The minerals identified through 

these efforts should be carefully and comprehensively characterized with respect to both structure and elemental composition. In the characterization of minerals, consideration should also 

be given to (1)  purity, (2)  particle morphology 

(range of dimensions and sizes), (3) surface area, 

(4) surface chemistry, and (5) surface reactivity. 

Care must be taken to ensure that a sufficient 

amount of the studied material is available, not 

only for current studies but also as reference material for possible future studies. The information 

developed from all of these efforts should be entered into a database, which can serve as a tool 

for selection of minerals for testing and validation of toxicological tests, as well as to assist in 

identification of worker populations for possible 

epidemiological studies. 

An objective of the proposed research is to 

achieve a level of mechanistic understanding 

that can provide a basis for developing biologically based models for extrapolating results of 

animal inhalation and other types of in vivo

studies to predict risks to worker health associated with exposure conditions typically encountered in workplaces. Little is known about 
96 NIOSH CIB 62 • Asbestos

the mechanisms by which asbestos fibers and 

some other EMPs cause lung cancer, mesothelioma, and nonmalignant respiratory diseases. 

As these mechanisms become understood, 

biologically based models can be developed to 

extrapolate from exposure-dose-response relationships observed in animals to estimates of 

disease risk in exposed humans. In addition, 

such studies would provide (1) an opportunity 

to measure molecular and cellular outcomes 

that can be used to determine why one animal 

species responds differently from another and 

(2) information on EMP characteristics associated with eliciting or potentiating various biological effects. The outcomes of these studies can 

then be evaluated in subsequent experiments to 

provide (1) risk assessors with a useful understanding of the various disease mechanisms by 

which animals respond to EMP exposures; and 

(2) regulatory agencies and industrial hygiene 

and occupational health professionals with information needed to implement appropriate 

exposure limits and risk management programs 

for monitoring worker exposure and health. 

It is anticipated that it may be difficult to find 

populations of workers that are exposed to EMPs 

with characteristics (e.g., dimension, composition) of interest that are sufficiently large to provide adequate statistical power, and where exposures are not confounded or where confounding 

can be effectively controlled in the analysis. 

NIOSH retains exposure information and, in 

some cases, personal air sample filters collected 

and archived from past epidemiological studies 

of workers exposed to asbestos. Such existing 

data might be used to update and extend findings from these studies. Where appropriately balanced epidemiological studies can be identified, 

it may be possible to conduct meta-analyses to 

investigate important EMP characteristics. The 

analysis of archived samples may help to elucidate 

how more detailed characteristics of exposure 

(e.g., particle dimension) relate to disease outcomes. New epidemiological (retrospective and 

prospective) studies should not be undertaken 

unless feasibility studies (e.g., preliminary assessments of study population size, exposure latencies, records of exposure, and confounders) have 

been appropriately considered. 

Because the opportunities for informative epidemiological studies are likely to be limited, 

it will be necessary to complement them with 

toxicological testing, and an integrated approach to toxicological research will be needed 

to understand how various types of EMPs induce disease. Where epidemiological studies of 

new cohorts are possible, or where epidemiological studies of previously studied cohorts 

can be updated, attempts should be made to 

link their results with those of toxicological 

studies to assess the ability of various types 

of toxicological testing to predict health outcomes in humans. Toxicological testing should 

be done with attention to collecting more specific information, including: (1) physical characteristics (e.g., dimension); (2) chemical composition; (3) in vitro acellular data (dissolution, 

durability); and (4) in vitro/in vivo cellular data 

(e.g., cytotoxicity, phagocytosis, chromosomal 

damage, mediator release). 

To help elucidate which physicochemical properties are important for inducing a biological effect, it may be necessary to generate exposures 

to EMPs of specific dimensions and composition. Several approaches are being pursued by 

NIOSH to overcome technological difficulties 

in generating sufficient quantities of well-characterized and dimensionally restricted EMPs. 

Efforts to generate mineral samples of appropriate particle-size dimensions by grinding techniques have met with some success but have 

not consistently generated EMPs in restricted 

size ranges of interest or in sufficient quantity 
NIOSH CIB 62 • Asbestos 97

to enable toxicity testing. Another approach has 

used a fiber size classifier [Deye et al. 1999], but 

this has not provided large enough quantities of 

EMPs for long-term inhalational exposure studies in animals. NIOSH researchers are currently 

evaluating the possibility of developing a fiber 

size classifier with increased output to generate 

much larger quantities of particles in restricted 

size ranges for toxicological testing.

An outcome of the proposed research programs 

should be an understanding of the relationships 

between and among the results of human observational studies and in vitro, short-term in vivo, 

and long-term in vivo experimental studies. 

Any research undertaken should be designed 

to ensure that results can be interpreted and 

applied within the context of other studies. For 

example, EMPs used in long-term animal inhalation studies should also be tested in in vitro/in 

vivo assay systems so that findings can be compared. The results of such experiments can help 

to develop and standardize in vitro/in vivo assay 

systems for use in predicting the potential toxicity of various types of EMPs. 

Government agencies, other organizations, 

and individual researchers have already recommended similar research strategies for evaluating the toxicity of mineral and synthetic fibers 

[Greim 2004; ILSI 2005; Mossman et al. 2007; 

Schins 2002; Vu et al. 1996]. These published 

strategies should be used as a foundation for 

developing a research program. 

Some research and improvements in sampling 

and analytical methods used to routinely assess 

exposures to EMPs can be done in the short 

term, and because the results of the toxicological 

studies provide a clearer understanding of EMP 

characteristics that determine toxicity, it will be 

necessary to ensure that the measurement techniques used in evaluating workplace exposures 

incorporate the exposure metrics used in determining the dose-response effect found in animal 

studies. The development of such exposure measurement techniques should (1) reduce the subjectivity inherent in current methods of particle 

identification and counting, (2) closely quantify 

EMPs on the basis of characteristics that are important to toxicity, and (3) reduce cost and shorten turnaround times in comparison with current 

EM methods. 

Toxicological, exposure assessment, and epidemiological research should be conducted with 

the overarching goal of developing information necessary for risk assessments. Although 

a framework for mineralogical research is not 

provided in this Roadmap, research providing a better understanding of mineralogical 

physicochemical properties will help inform the 

risk assessment process. Improved risk assessments and analytical methodology are needed 

to inform the development of new and revised 

occupational exposure limits for control of exposures associated with the production of EMPcaused disease. 

For those individuals who have an asbestosrelated disease or are at high risk of developing 

an asbestos-related disease, research is needed 

to improve methods and clinical guidance for 

screening, diagnosis, secondary prevention, and 

treatment of EMP-caused diseases. The development and validation of biomarkers of disease 

and improved lung-imaging technologies can 

lead to earlier diagnosis of asbestos-related disease. It will also be important to advance knowledge on how to effectively treat EMP-caused 

diseases, especially malignant mesothelioma, 

which is fatal in most cases. Accomplishing the 

goals of early diagnosis and development of 

treatment options can improve the quality and 

quantity of life for those who develop asbestosrelated disease.

NIOSH CIB 62 • Asbestos 99

4 The Path Forward

Developing an interdisciplinary research program and prioritizing research projects to 

implement the research agenda envisioned in 

this Roadmap will require a substantial investment of time, scientific talent, and resources 

by NIOSH and its partners. However, achieving the proposed goals will be well worth the 

investment because it will improve the quality 

of life of U.S. workers by preventing workplace 

exposure to potentially hazardous EMPs, and it 

will reduce future healthcare costs. As with any 

strategic approach, unintended and unforeseen 

results and consequences will require program 

adjustments as available resources change, information is produced, and time goes on.

4.1 Organization of the 

Research Program

To ensure that the scientific knowledge created 

from implementation of this Roadmap is applied as broadly as possible, NIOSH plans to 

partner with other federal agencies, such as the 

Agency for Toxic Substances and Disease Registry (ATSDR), the Consumer Product Safety 

Commission (CPSC), the Environmental Protection Agency (EPA), the Mine Safety and 

Health Administration (MSHA), the National 

Institute of Standards and Technology (NIST), 

the National Institute of Environmental Health 

Sciences (NIEHS), the National Toxicology 

Program (NTP), the Occupational Safety and 

Health Administration (OSHA), and the United States Geological Survey (USGS), as well as 

with labor, industry, academia, practitioners, 

and other interested parties including international groups. Partnerships and collaborations 

will be used to help focus the scope of the research to be undertaken, enhance extramural 

research activities, and assist in the development and dissemination of educational materials describing the outcomes of the research and 

their implications for occupational and public 

health policies and practices.

Some of the next steps in development will involve organizing study groups with representatives from federal agencies, industry, academia, 

and workers’ organizations to identify specific 

priorities for the programs developed within 

the overarching research framework. Study 

groups should be assembled from among the 

partners to identify specific research elements 

needed to address the information gaps and 

data needs outlined in this Roadmap. Although 

it may be appropriate to organize separate 

study groups around the scientific disciplines 

needed to conduct the research—such as epidemiology, toxicology, exposure assessment, 

mineralogy, and particle characterization and 

analysis—and to conduct the risk assessments, 

each of the study groups will need to include 

members from other disciplines to ensure the 

multidisciplinary nature of the research is considered and addressed. Also important will be 

coordination between and among study groups 

to ensure the efforts in the various research 

areas are complementary and move toward 

common goals and the eventual development 

of sufficient information for risk assessment. 

These study groups should be maintained over 

the lifetime of the research program to oversee 

and help guide the research. An independent 

group could provide oversight of the overall 
100 NIOSH CIB 62 • Asbestos

research effort, periodically reviewing the various discipline-specific research programs to 

help ensure that the most appropriate research 

is accomplished in a timely and coordinated 

manner and to help maintain the scientific 

quality of the research.

4.2 Research Priorities

The key issues discussed in Section 2.10 include 

several research needs: (1) for the asbestos minerals, development of a clearer understanding of 

the important dimensional and physicochemical determinants of pathogenicity; (2) for other 

EMPs, such as those from nonasbestiform habits of the asbestos minerals and erionite, development of a deeper understanding of the determinants of toxicity; and (3) development of 

analytical methods that can differentiate EMPs 

and quantify airborne exposures to EMPs. To 

begin addressing these issues, infrastructure 

projects should be developed and initiated with 

input from the study groups.

One such infrastructure project is the development of a standardized set of terms that can be 

used to clearly and precisely describe minerals 

and other scientific concepts. This is needed to 

help with the planning of research projects and 

to effectively communicate research results. 

This effort should involve representatives from 

each of the relevant scientific disciplines.

Another infrastructure project that should be 

considered at the onset of prioritizing research 

is the development of criteria and logistics for 

establishing a mineral reference repository. Initially, representative samples from the known 

asbestos deposits should be procured and carefully and comprehensively characterized. If 

samples of these repository minerals are further processed in the course of conducting research, the processed materials will need to be 

fully characterized as well. Concomitant with 

this characterization effort should be the development of a mineralogical research effort addressing issues pertaining to the identification 

of minerals that might be found on airborne 

samples collected at various workplace environments and to develop further and deeper understanding of mineralogical properties that may 

contribute to the toxicity of particles. 

One of the earliest research efforts will be preliminary systematic collection and evaluation 

of available information on (1) industries/occupations/job tasks/processes with exposure to 

various types of asbestos fibers and other EMPs, 

(2) numbers of workers exposed, (3) characteristics and levels of exposures, and (4) associated 

particulate exposures. The knowledge generated 

from these efforts will be needed to identify the 

EMPs that workers are exposed to and worker 

populations that have the potential to be included in epidemiological studies. In addition to ascertaining EMP exposures and EMP-exposed 

populations in the United States, networking 

and other tools should be used to identify potential international populations for epidemiological studies. Representative samples of the 

EMPs identified through these efforts should 

be procured, characterized, and included in the 

mineralogical reference repository. After thorough characterization, these samples can be 

classified and prioritized for use in the toxicological studies. 

A part of this early effort should be the development of a comprehensive and integrated 

public-use information management system to 

warehouse (1) the mineral characterization information generated on the reference samples; 

(2) data generated from hazard and health surveillance activities; (3) information on the minerals tested and the methods used, as well as 

the results of toxicological studies; and (4) the 

data gathered from epidemiological and other 
NIOSH CIB 62 • Asbestos 101

surveillance investigations. By having the results of previous studies available in the information management system, it could be used to 

promote the development of an efficient, nonduplicative research program. It could also be 

a resource for data exploration and additional 

analyses of accumulated results. 

After comprehensive review of current knowledge and the available data in the abovedescribed information management system, 

the study groups should identify specific aims 

and plan, prioritize, and conduct mineralogical, toxicological, epidemiological, and clinical 

research within the general framework laid out 

in this Roadmap. Early results will inform the 

need for later research and will dictate changes 

in priorities and directions needed to accomplish the overall goals of the research program. 

Ongoing research and study on improvements 

of the analytical methods currently used for 

regulatory purposes should be independent of 

other research. However, as surveillance and 

exposure assessment efforts proceed, research 

on analytical methods should advance the capability to identify and characterize worker exposures and to measure relevant exposure parameters identified by toxicological research. 

Eventually, after determinants of EMP toxicity are more fully elucidated, research should 

increasingly focus on sampling and analytical 

methods that can be routinely used in compliance exposure assessment. 

4.3 Outcomes

NIOSH will promote integration of the research goals set forth in this Roadmap into 

the industry sector–based and research-topractice-focused National Occupational Research Agenda (NORA), a national program 

involving both the public and private sectors. 

The goals and objectives of this Roadmap

can be substantially advanced through robust 

public-private sector partnership.

The ideal outcome of a comprehensive research 

program for asbestos fibers and other EMPs 

would be to use the results to develop recommendations to protect workers’ health that are 

based on unambiguous science. Optimally, such 

recommendations may specify criteria, such as 

a range of chemical composition, dimensional 

attributes (e.g., ranges of length, width, and aspect ratio), dissolution rate/fragility parameters, 

and other factors that can be used to indirectly 

assess the toxicity of EMPs. It would be particularly advantageous if the results of the research 

could be used to devise a battery of validated 

in vitro or short-term in vivo assays with sufficient predictive value to identify EMPs warranting concern on the basis of their physical 

and chemical properties, without the need for 

comprehensive toxicity testing and/or epidemiological evaluation of each individual EMP. 

Newly identified EMPs could be compared to 

the criteria to determine a likelihood of toxicity. Coherent risk management approaches for 

EMPs that fully incorporate a clear understanding of the toxicity could then be developed to 

minimize the potential for EMP-related disease 

outcomes among exposed workers. 

Although it is beyond the scope of this Roadmap, exploration of the extent to which a 

health-protective policy for EMPs could be extended to SVFs and other manufactured materials, such as engineered carbon nanotubes 

and nanofibers, is warranted. It has been noted 

that elongate nanoscale particles (e.g., singlewalled and multiwalled carbon nanotubes) 

cause interstitial fibrosis in mice [Shvedova et 

al. 2005; Porter et al. 2009] and that peritoneal exposure of mice to carbon nanotubes has 

been reported to induce pathological responses 
102 NIOSH CIB 62 • Asbestos

similar to those caused by asbestos, suggesting 

potential for induction of mesothelioma [Poland et al. 2008]. Recommendations have been 

made elsewhere to systematically investigate 

the health effects of these manufactured nanomaterials within the next five years [Maynard 

et al. 2006; NIOSH 2008b]. Integrating results 

of nanoparticle toxicity investigations with the 

results of the research program developed as a 

result of this Roadmap may lead to a broader 

and more fundamental understanding of the 

determinants of toxicity of EPs.

Working toward achieving the goals delineated 

in this Roadmap is consonant with NIOSH’s 

statutory mission to generate new knowledge 

in the field of occupational safety and health 

and to transfer that knowledge into practice for 

the benefit of workers. Advancing knowledge 

relevant for use in protecting workers from 

adverse health effects arising from exposure 

to asbestos fibers and other EMPs is the ultimate goal. Though further scientific research 

conducted by NIOSH will continue to focus on 

the occupational environment, NIOSH intends 

to pursue partnerships to ensure that scientific 

research arising from this Roadmap will comprise an integrated approach to understanding 

and limiting EMP hazards incurred not only in 

work settings, but also in the general community and the general environment. 

As information becomes available from research activities, NIOSH plans to assist in the 

development and dissemination of educational 

materials describing the outcomes of the research and their implications for occupational 

and public health policies and practices.
NIOSH CIB 62 • Asbestos 103

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growth habit of asbestos and the dimensions of 

asbestos fibers. Presented at the SME Annual 

Meeting, Phoenix, AZ, January 25–28.

Wylie AG, Bailey KF [1992]. The mineralogy 

and size of airborne chrysotile and rock fragments: ramifications of using the NIOSH 7400 

method. Am Ind Hyg Assoc J 53:442–447.

Wylie AG, Virta RL, Russek E [1985]. Characterizing and discriminating airborne amphibole cleavage fragments and amosite fibers: 

implications for the NIOSH method. Am Ind 

Hyg Assoc J 46:197–201.

Wylie AG, Virta RL, Segreti JM [1987]. Characterization of mineral population by index 

particle: implications for the Stanton hypothesis. Environ Res 43:427–439.

Wylie AG, Bailey KF, Kelse JW, Lee RJ [1993]. 

The importance of width in asbestos fiber carcinogenicity and its implications for public 

policy. Am Ind Hyg Assn J 54:239–252.

Wylie AG, Skinner HC, Marsh J, Snyder H, 

Garzione C, Hodkinson D, Winters R, Mossman BT [1997]. Mineralogical features associated with cytotoxic and proliferative effects 

of fibrous talc and asbestos on rodent tracheal 

epithelial and pleural mesothelial cells. Toxicol 

Appl Pharmacol 147:143–150.

Yamaguchi R, Hirano T, Ootsuyama Y, Asami S, Tsurudome Y, Fukada S, Yamato H, Tsuda T, Tanaka I, Kasai H [1999]. Increased 8-hydroxyguanine in DNA and its repair activity in 

hamster and rat lung after intratracheal instillation of crocidolite asbestos. Jpn J Cancer Res 

90:505–509.

Yang H, Bocchetta M, Kroczynska B, Elmishad 

AG, Chen Y, Liu Z, Bubici C, Mossman BT, Pass 

HI, Testa JR, Franzoso G, Carbone M [2006]. 

TNF-α inhibits asbestos-induced cytotoxicity via a NF-κB-dependent pathway, a possible 

mechanism for asbestos-induced oncogenesis. 

Proc Natl Acad Sci USA 103:10397–10402.
NIOSH CIB 62 • Asbestos 129

Yano E, Wang Z, Wang X [2001]. Cancer mortality among workers exposed to amphibole-free 

chrysotile asbestos. Am J Epidemiol 154:538–

543.

Yu CP, Asgharian B, Yen BM [1986]. Impaction 

and sedimentation deposition. Am Ind Hyg Assoc J 47:72–77.

Zeidler-Erdely PC, Calhoun WJ, Amercedes 

BT, Clark MP, Deye GJ, Baron P, Jones W, Blake 

T, Castranova V [2006]. In vitro cytotoxicity of 

Manville Code 100 glass fibers: effect of fiber 

length on human alveolar macrophages. Part 

Fibre Toxicol 3:5–11.

Zhou Y, Su WC, Cheng YS [2007]. Fiber deposition in the tracheobronchial region: experimental 

measurements. Inhal Toxicol 19:13, 1071–1078.

Zodac P [1940]. A talc quarry near Chester, 

Vermont. Rocks and Minerals 15:369–371.

Zoltai T [1981]. Amphibole asbestos mineralogy. In: Veblen DR, ed. Amphiboles and other 

hydrous pyriboles. Rev Mineral 9A:237–278.

Zumwalde RD, Ludwig HR, Dement JM [1981]. 

Industrial hygiene report, Homestake Mining Company, Lead, South Dakota. Cincinnati, OH: U.S. Department of Health and Human 

Services, Centers for Disease Control, National Institute for Occupational Safety and Health. 

NTIS #PB85–243640, pp. 255.

NIOSH CIB 62 • Asbestos 131

6 Glossary

6.1 NIOSH Definition of 

Potential Occupational 

Carcinogen

Potential Occupational Carcinogen means any 

substance, or combination or mixture of substances, which causes an increased incidence of 

benign and/or malignant neoplasms, or a substantial decrease in the latency period between 

exposure and onset of neoplasms in humans 

or in one or more experimental mammalian 

species as the result of any oral, respiratory or 

dermal exposure, or any other exposure which 

results in the induction of tumors at a site other 

than the site of administration. This definition 

also includes any substance which is metabolized into one or more potential occupational 

carcinogens by mammals.

6.2 Definitions of New Terms 

Used in this Roadmap

Countable elongate mineral particle: A particle 

that meets specified dimensional criteria and is to 

be counted according to an established protocol. 

A countable elongate mineral particle under the 

NIOSH REL for Airborne Asbestos Fibers and Related Elongate Mineral Particles is any asbestiform 

fiber, acicular or prismatic crystal, or cleavage fragment of a covered mineral that is longer than 5 μm 

and has a minimum aspect ratio of 3:1 on the basis 

of a microscopic analysis of an air sample using 

NIOSH Method 7400 or an equivalent method.

Covered mineral: A mineral encompassed by a 

specified regulation or recommended standard. 

Under the NIOSH REL for Airborne Asbestos 

Fibers and Related Elongate Mineral Particles, 

covered minerals include those minerals having the crystal structure and elemental composition of the asbestos varieties (chrysotile, 

riebeckite asbestos [crocidolite], cummingtonitegrunerite asbestos [amosite], anthophyllite 

asbestos, tremolite asbestos, and actinolite asbestos) or their nonasbestiform analogs (the 

serpentine minerals antigorite and lizardite 

and the amphibole minerals contained in the 

cummingtonite-grunerite mineral series, the 

tremolite-ferroactinolite mineral series, and the 

glaucophane-riebeckite mineral series).

Elongate mineral particle (EMP): Any mineral particle with a minimum aspect ratio of 

3:1. This Roadmap is focused on EMPs that are 

of inhalable, thoracic, or respirable size, as described below in Section 6.2. 

Elongate particle (EP): Any particle with a 

minimum aspect ratio of 3:1. The research described in this Roadmap is focused on EPs that 

are of inhalable, thoracic, or respirable size, as 

described below in Section 6.2.

6.3 Definitions of 

Inhalational Terms

Inhalable particulate matter: Particles that 

deposit anywhere in the respiratory tract.

This varies by species, but for humans such 

matter can be approximated as those particles 

captured according to the following collection 
132 NIOSH CIB 62 • Asbestos

efficiency, regardless of sampler orientation with 

respect to wind direction: 

IPM(dae) = 0.5 (1 + exp[−0.06 dae]) ± 10; for 

0 < dae ≤ 100 μm

Where IPM(dae) = the collection efficiency 

and dae is the aerodynamic diameter in μm. 

[ACGIH 1999]

Respirable particulate matter: Particles that 

deposit anywhere in the gas-exchange region of the lung. This varies by species, but 

for humans such matter can be approximated 

as those particles captured according to the 

following collection efficiency: RPM(dae) = 

IPM(dae)[1−F(x)]

Where F(x) = cumulative probability function of the standardized normal variable, x. 

x = ln(dae/4.25 μm)/ln(1.5) [ACGIH 1999]

Thoracic particulate matter: Particles that 

deposit anywhere within the lung airways and 

the gas-exchange region. This varies by species, 

but for humans such matter can be approximated as those particles captured according to 

the following capture efficiency: TPM(dae) = 

IPM(dae)[1−F(x)]

Where F(x) = cumulative probability function of the standardized normal variable, x 

x = ln(dae/11.64 μm)/ln(1.5) [ACGIH 1999]

6.4 Definitions of General 

Mineralogical Terms 

and Specific Minerals

Definitions from several sources are provided in 

the following tables for many of the mineralogical 

terms used in this Roadmap. Definitions of 

some terms in this table differ. Also, definitions 

of these same terms, as used by various authors 

whose work has been cited in this Roadmap, 

may vary from those provided here. It is not 

possible to know and/or provide each of the 

variant definitions.

6.5 References for Definitions 

of General Mineralogical 

Terms, Specific Minerals, 

and Inhalational Terms

ACGIH (American Conference of Governmental 

Industrial Hygienists) [1999]. Particle size–selective 

sampling for particulate air contaminants. Vincent 

JH, ed. Cincinnati, OH: ACGIH.

American Geological Institute [2005]. Glossary of Geology, 5th ed. Neuendorf KKE, Mehl 

JP, Jackson JA, eds. Alexandria, VA: American 

Geological Institute.

Leake BE, Woolley AR, Arps CES, Birch WD, 

Gilbert CM, Grice JD, Hawthorne FC, Kato A, 

Kisch HF, Krivovichev VG, Linthout K, Laird J, 

Mandarino JA, Maresch WV, Nickel EH, Rock 

NMS, Schumacher JC, Smith DC, Stephenson 

NCN, Ungaretti L, Whittaker EJW, Youzhi G 

[1997]. Nomenclature of the amphiboles: report of the Subcommittee on Amphiboles of 

the International Mineralogical Association 

Commission on new minerals and mineral 

names. Can Mineral 35:219–246.

NIOSH [1990a]. Comments of the National 

Institute for Occupational Safety and Health 

on the Occupational Safety and Health Administration’s Notice of Proposed Rulemaking on 

Occupational Exposure to Asbestos, Tremolite, 

Anthophyllite, and Actinolite. OSHA Docket 
NIOSH CIB 62 • Asbestos 133

No. H-033d, April 9, 1990 [http://www.cdc.

gov/niosh/review/public/099/pdfs/AsbestosTestimony_April%209_1990.pdf]. Date accessed: December 17, 2009.

U.S. Bureau of Mines [1996]. Dictionary of 

mining, mineral, and related terms. 2nd ed 

[http://xmlwords.infomine.com/USBM.htm]. 

Date accessed: December 18, 2009.
134 NIOSH CIB 62 • Asbestos Table 1. Definitions of general mineralogical terms Term Dictionary of Mining, Mineral, and Related Terms [U.S. Bureau of Mines 1996] [Note: Footnotes identify the Primary Source Citation for the definition] Glossary of Geology, 5th ed. [American Geological Institute 2005] Leake et al. [1997] NIOSH [1990a] Acicular1 1. A mineral consisting of fine needlelike crystals, e.g., natrolite. 2. Slender needlelike crystal. 3. Refers to needlelike crystals.2 [crystal]: Said of a crystal that is needlelike in form. Amphibole A mineral group; characterized by double chains of silica tetra- hedra having the composition 

A0-1

B

Y2 Z5 O8 22(OH,F,Cl) , where 

(A = Ca,Na,K,Pb,B), (B = Ca,Fe,Li,Mg,Mn,Na), (Y = Al,Cr,Fe,Mg,Mn,Ti), and (Z = Al,Be,Si,Ti); in the orthorhombic or monoclinic crystal systems, including actinolite, anthophyllite, arfvedsonite, cummingtonite, hornblende, richterite, glaucophane, grunerite, anthophyllite, riebeckite, tremolite, and others. All display a diagnostic prismatic cleavage in two directions parallel to crystal faces and intersecting at angles of about 54° and 124°. Some members may be asbestiform.

1. A group of dark [sic] rock-forming ferromagnesian silicate minerals, closely related in crystal form and composition and having the general formula: A2-3

B5(Si,Al)

O8 22(OH)2, where A = Mg, 

Fe2+, Ca, or Na, and B = Mg, Fe2+, Fe3+, Li, Mn, or Al. It is characterized by a cross-linked double chain of tetrahedral with silicon:oxygen ratio of 4:11, by columnar or fibrous prismatic crystals, and by good prismatic cleavage in two directions parallel to the crystal faces and intersecting at angles of 56° and 124°; colors range from white to black. Most amphiboles crystallize in the monoclinic system, some in the orthorhombic. They constitute an abundant and widely distributed constituent in igneous and metamorphic rocks (some are wholly metamorphic), and they are analogous in chemical composition to the pyroxenes.2. A mineral of the amphibole group, such as hornblende, anthophyllite, cummingtonite, tremolite, actinolite, riebeckite, glaucophane, arfvedsonite, etc.

A mineral comprising a double silicate chain with the general formula AB2VI

C5IV

T

O8 22(OH)2 with 

the components of the formula conventionally described as 

A, B, C, 

T and “OH” corresponding to the following crystallographic sites:A one site per formula unit; 

B two 

M4 sites per formula unit; 

C a 

composite of five sites made up of 2 M1, 2 

M2 and 1 

M3 sites per formula 

unit; 

T eight sites, in two sets of 

four, that need not be distinguished; “OH” two sites per formula unit.The ions considered normally to occupy these sites are in the following categories: (empty site) and K at A only; Na at 

A or 

B; Ca at 

B only; 

L-type ions: Mg, Fe2+, Mn2+, Li and rarer ions of similar size, at 

C or 

B; 

M-type ions: Al at 

C or 

T, Fe3+ and, 

more rarely Mn3+, Cr3+ at 

C only; 

high-valency ions: Ti4+ at 

C or 

T, Zr4+

at 

C only, Si at 

T only; anions: OH, F, 

Cl, O at “OH”. 

M-type ions normally 

occupy 

M2 sites and so are normally 

limited to two of the five 

C sites. 

Minerals in the amphibole group are widely distributed in the earth’s crust in many igneous or metamorphic rocks. In some instances, the mineral deposits contain sufficient quantities of the asbestiform minerals to be economically minable for commercial use. The minerals and mineral series of the amphibole group have variable compositions with extensive elemental substitutions. They are found in forms ranging from massive to fibrous. The most common commercially exploited asbestiform varieties of this mineralogical group include crocidolite, amosite, anthophyllite, tremolite, and actinolite. Crocidolite, amosite, and anthophyllite are selectively mined for commercial use, whereas tremolite and actinolite are most often found as a contaminant in other mined commodities such as talc and vermiculite. The amphiboles have good thermal and electrical insulation properties, and they have moderate to good resistance to acids.

 See footnotes at end of table. (Continued)
NIOSH CIB 62 

• Asbestos 135

Table 1. Definitions of general mineralogical terms (Continued)

Term

Dictionary of Mining, 

Mineral, and Related 

Terms [U.S. Bureau 

of Mines 1996]

[Note: Footnotes identify the Primary Source Citation for the definition]

Glossary of Geology, 5th ed.

[American Geological 

Institute 2005] Leake et al. [1997] NIOSH [1990a]

Amphibole(Continued)

3. A term sometimes used a synonym for hornblende. Etymol: Greek “amphibolos”, “ambiguous, doubtful”, in reference to its many varieties.

Exceptions may occur to the above “normal” behavior. Four groups are classified depending on the occupancy of the B sites: Mg-Fe-MnLi group; calcic group; sodic-calcic group; and sodic group. Asbestiform amphiboles should be named according to their precise mineral name (when known) followed by the suffix—asbestos, e.g., anthophylliteasbestos, tremolite-asbestos. 

Asbestiform1 1. Said of a mineral that is 

fibrous, i.e., like asbestos.

Said of a mineral that is composed of separable fibers.

A specific type of mineral fibrosity in which the growth is primarily in one dimension and the crystals form naturally as long, flexible fibers. Fibers can be found in bundles that can be easily separated into smaller bundles or ultimately into fibrils. 

 See footnotes at end of table. (Continued)
136 NIOSH CIB 62 • Asbestos Table 1. Definitions of general mineralogical terms (Continued) Term Dictionary of Mining, Mineral, and Related Terms [U.S. Bureau of Mines 1996] [Note: Footnotes identify the Primary Source Citation for the definition] Glossary of Geology, 5th ed. [American Geological Institute 2005] Leake et al. [1997] NIOSH [1990a] Asbestos1 1. A commercial term applied to silicate minerals that separate readily into thin, strong fibers that are flexible, heat resistant, and chemically inert, thus making them suitable for uses (as in yarn, cloth, paper, paint, brake linings, tiles, insulation, cement, fillers, and filters) where incombustible, nonconducting, or chemically resistant material is required. Since the early 1970’s, there have been serious environmental concerns about the potential health hazards of asbestos products, which has resulted in strong environmental regulations. 1. A commercial term applied to a group of silicate minerals that readily separate into thin, strong fibers that are flexible, heat resistant, and chemically inert, and are therefore suitable for uses (as in yarn, cloth, paper, paint, brake linings, tiles, insulation, cement, fillers, and filters) where incombustible, nonconducting, or chemically resistant material is required. 2. A mineral of the asbestos group [sic], principally chrysotile (best adapted for spinning) and certain fibrous varieties of amphibole (esp. amosite, anthophyllite, and crocidolite). 3. A term strictly applied to the fibrous variety of actinolite. Certain varieties are deleterious to health. Asbestos is a generic term for a number of silicate minerals with a fibrous crystalline structure. The quality of commercially used asbestos depends on the mineralogy of the asbestiform variety, the degree of fiber development, the ratio of fibers to acicular crystals or other impurities, and the length and flexibility of the fibers. The asbestiform varieties of these minerals can be found in both the amphibole and serpentine mineral groups. The asbestiform varieties occur in veins or small veinlets within rock containing or composed of the common (nonasbestiform) variety of the same mineral. 2. Any asbestiform mineral of the serpentine group (chrysotile, best adapted for spinning and the principal variety in commerce) or amphibole group (esp. actinolite, anthophyllite, gedrite, cummingtonite, grunerite, riebeckite, and tremolite). 3. A term strictly applied to asbestiform actinolite. The major asbestiform varieties of minerals used commercially are chrysotile, tremolite-actinolite asbestos, cummingtonite-grunerite asbestos, anthophyllite asbestos, and crocidolite. Asbestos is marketed by its mineral name (e.g., anthophyllite asbestos), its variety name (e.g., chrysotile or crocidolite), or its trade name (e.g., Amosite). 

 See footnotes at end of table. (Continued)
NIOSH CIB 62 • Asbestos 137 Table 1. Definitions of general mineralogical terms (Continued) Term Dictionary of Mining, Mineral, and Related Terms [U.S. Bureau of Mines 1996] [Note: Footnotes identify the Primary Source Citation for the definition] Glossary of Geology, 5th ed. [American Geological Institute 2005] Leake et al. [1997] NIOSH [1990a] Cleavage fragment1 A fragment of a crystal that is bounded by cleavage faces. A fragment produced by the breaking of crystals in directions that are related to the crystal structure and are always parallel to possible crystal faces. Minerals with perfect cleavage can produce perfect regular fragments. Amphiboles with prismatic cleavage will produce prismatic fragments. Note: These fragments can be elongated and may meet the definition of a fiber upon microscopic examination. Crystal habit The forms typically appearing on specimens of a mineral species or group, rarely all the forms permitted by its point group. Crystal habits range from highly diverse, e.g., calcite, to almost never showing crystal faces, e.g. turquoise. The general shape of crystals, e.g. cubic, prismatic, fibrous. For a given type of crystal, the habit may vary from locality to locality depending on environment of growth. In addition to describing mineral habits with form names, e.g. prismatic, pyramidal, or tetrahedral, other names for appearances are used, e.g. fibrous, columnar, platy, or botryoidal. Intergrowths are given by specific description.3 See footnotes at end of table. (Continued)
138 NIOSH CIB 62 

• Asbestos

Table 1. Definitions of general mineralogical terms (Continued)

Term

Dictionary of Mining, 

Mineral, and Related 

Terms [U.S. Bureau 

of Mines 1996]

[Note: Footnotes identify the Primary Source Citation for the definition]

Glossary of Geology, 5th ed.

[American Geological 

Institute 2005] Leake et al. [1997] NIOSH [1990a]

Fiber1 The smallest single strand 

of asbestos or other fibrous material.4

A strengthening cell, usually elongated, tapering, and thick-walled, occurring in various parts of vascular plants. [Note: The definition provided does not refer to mineral fibers.]

An acicular single crystal or similarly elongated polycrystalline aggregate particles. Such particles have macroscopic properties such as flexibility, high aspect ratio, silky luster, and axial lineation. These particles have attained their shape primarily because of manifold dislocation planes that are randomly oriented in two axes but parallel in the third. Note: Upon microscopic examination, only particles that have a 3:l or greater aspect ratio are defined as fibers. Other macroscopic properties used to define fibers cannot be ascertained for individual particles examined microscopically. 

Fibril1 1. A single fiber which 

cannot be separated into smaller components without losing its fibrous properties or appearance.5

A single fiber that cannot be separated into smaller components without losing its fibrous properties or appearances.

Fibrous1 1. Applied to minerals 

that occur as fibers, such as asbestos.Syn: asbestiform2. Consisting of fine threadlike strands, e.g., satin spar variety of gypsum.

 See footnotes at end of table. (Continued)
NIOSH CIB 62 

• Asbestos 139

Table 1. Definitions of general mineralogical terms (Continued)

Term

Dictionary of Mining, 

Mineral, and Related 

Terms [U.S. Bureau 

of Mines 1996]

[Note: Footnotes identify the Primary Source Citation for the definition]

Glossary of Geology, 5th ed.

[American Geological 

Institute 2005] Leake et al. [1997] NIOSH [1990a]

Fibrous habit The tendency of certain minerals, 

e.g., asbestos, to crystallize in needlelike grains or fibers.

Fibrous structure If the crystals in a mineral 

aggregate are greatly elongated and have a relatively small cross-section, the structure or texture is fibrous. The fibers may be parallel, as in crocidolite and sometimes in calcite and cerussite. When the fibers are very fine, they may impart a silky luster to the aggregate, as in crocidolite or satin-spar gypsum. There is also a feltlike type. Fibrous crystals may radiate from a center, forming asteriated or starlike groups, either coarse or fine, as frequently observed in pyrolusite, wavellite, natrolite and tourmaline, and sometimes in stibnite and other minerals. Also called fibrous texture.6

Fibrous prismatic structure: A prismatic structure in which each firstorder prism is like a simple prism in showing nonspherulitic prismatic and noncomposite prismatic substructure, but the prisms have much higher length/width ratios than typical simple prisms, occurring as long fibers.

Fibrous texture In mineral deposits, a pattern 

of finely acicular, rod-like crystals, e.g., in chrysotile and amphibole asbestos.7

In mineral deposits, a pattern of finely acicular, rod-like crystals, e.g., in chrysotile and amphibole asbestos.

 See footnotes at end of table. (Continued)
140 NIOSH CIB 62 • Asbestos Table 1. Definitions of general mineralogical terms (Continued) Term Dictionary of Mining, Mineral, and Related Terms [U.S. Bureau of Mines 1996] [Note: Footnotes identify the Primary Source Citation for the definition] Glossary of Geology, 5th ed. [American Geological Institute 2005] Leake et al. [1997] NIOSH [1990a] Mineral 1. A naturally occurring inorganic element or compound having an orderly internal structure and characteristic chemical composition, crystal form, and physical properties. CF: metallic. 2. In miner’s phraseology, ore. See also: ore. 1. A naturally occurring inorganic element or compound having a periodically repeating arrangement of atoms and characteristic chemical composition, resulting in distinctive physical properties. A homogeneous, naturally occurring, inorganic crystalline substance. Minerals have distinct crystal structures and variation in chemical composition, and are given individual names. 3. See: mineral species; mineral series; mineral group. 4. Any natural resource extracted from the earth for human use; e.g., ores, salts, coal, or petroleum. 5. In flotation, valuable mineral constituents of ore as opposed to gangue minerals. 6. Any inorganic plant or animal nutrient. 7. Any member of the mineral kingdom as opposed to the animal and plant kingdoms.7 2. An element or chemical compound that is crystalline and formed as a result of geologic processes. Materials formed by geological processes from artificial substances are no longer accepted (after 1995) as new minerals (Nickel, 1995). Mercury, a liquid, is a traditional exception to the crystallinity rule. Water is not a mineral (although ice is), and crystalline biological and artificial materials are not minerals (cf. mineraloid). 3. Any naturally formed inorganic material, i.e., a member of the mineral kingdom as opposed to the plant or animal kingdom. See footnotes at end of table. (Continued)
NIOSH CIB 62 

• Asbestos 141

Table 1. Definitions of general mineralogical terms (Continued)

Term

Dictionary of Mining, 

Mineral, and Related 

Terms [U.S. Bureau 

of Mines 1996]

[Note: Footnotes identify the Primary Source Citation for the definition]

Glossary of Geology, 5th ed.

[American Geological 

Institute 2005] Leake et al. [1997] NIOSH [1990a]

Mineral series A mineral series includes two or 

more members of a mineral group in which the cations in secondary structural position are similar in chemical properties and can be present in variable but frequently limited ratios (e.g., cummingtoniteactinolite). The current trend in referring to a mineral series is to simplify long series names by using the mineral name of only one (end or intermediate) member (i.e., tremolite-actinolite-ferroactinolite).

Mineral variety The variety distinguishes minerals 

that are conspicuously different from (1) those considered normal within the common crystallization I habits, polytypes, and other structural variants, and (2) those with different physical properties such as color. Varieties are named by mineralogists, miners, gemologists, manufacturers of industrial products, and mineral collectors.

Needle 5. A needle-shaped or 

acicular mineral crystal.

[crystal]: A needle-shaped or acicular mineral crystal.

 See footnotes at end of table. (Continued)
142 NIOSH CIB 62 

• Asbestos

Table 1. Definitions of general mineralogical terms (Continued)

Term

Dictionary of Mining, 

Mineral, and Related 

Terms [U.S. Bureau 

of Mines 1996]

[Note: Footnotes identify the Primary Source Citation for the definition]

Glossary of Geology, 5th ed.

[American Geological 

Institute 2005] Leake et al. [1997] NIOSH [1990a]

Nonasbestiform habit

Each of the six commercially exploited asbestiform minerals also occurs in a nonasbestiform mineral habit. These minerals have the same chemical formula as the asbestiform variety, but they have crystal habits where growth proceeds in two or three dimensions instead of one dimension. When milled, these minerals do not break into fibrils but rather into fragments resulting from cleavage along the two or three growth planes. Particles thus formed are referred to as cleavage fragments and can meet the definition of a fiber for regulatory purposes. 

Prism 1. An open crystal form with 

faces and their intersecting edges parallel to the principle crystallographic axis. Prisms have three (trigonal), four (tetragonal), six (ditrigonal or hexagonal), eight (ditetragonal), or twelve (dihexagonal) faces. The ninesided prisms of tourmaline are a combination of trigonal and hexagonal prisms.

[crystal] A crystal form having three, four, six, eight, or twelve faces, with parallel intersection edges, and which is open only at the two ends of the axis parallel to the intersection edges of the faces.

 See footnotes at end of table. (Continued)
NIOSH CIB 62 

• Asbestos 143

Table 1. Definitions of general mineralogical terms (Continued)

Term

Dictionary of Mining, 

Mineral, and Related 

Terms [U.S. Bureau 

of Mines 1996]

[Note: Footnotes identify the Primary Source Citation for the definition]

Glossary of Geology, 5th ed.

[American Geological 

Institute 2005] Leake et al. [1997] NIOSH [1990a]

Prismatic 2. Pertaining to a 

crystallographic prism.3. Descriptive of a crystal with one dimension markedly longer than the other two.4. Descriptive of two directions of cleavage.

[crystal] Said of a crystal that shows one dimension markedly longer than the other two.

Serpentine Minerals

A rock consisting almost wholly of serpentine-group minerals, e.g., antigorite, chrysotile, or lizardite, derived from the hydration of ferromagnesian silicate minerals such as olivine and pyroxene. Accessory chlorite, talc, and magnetite may be present. 

The serpentine minerals belong to the phyllosilicate group of minerals. The commercially important variety is chrysotile, which originates in the asbestiform habit. Antigorite and lizardite are two other types of serpentine minerals that are structurally distinct. The fibrous form of antigorite is called picrolite. 

 See footnotes at end of table. (Continued)
144 NIOSH CIB 62 • Asbestos Table 1. Definitions of general mineralogical terms (Continued) Term Dictionary of Mining, Mineral, and Related Terms [U.S. Bureau of Mines 1996] [Note: Footnotes identify the Primary Source Citation for the definition] Glossary of Geology, 5th ed. [American Geological Institute 2005] Leake et al. [1997] NIOSH [1990a] Zeolite 1. A generic term for class of hydrated silicates of aluminum and either sodium or calcium or both, of the type Na O. 2 Al

O2 3.nSiO2

•xH O. The term 2

originally described a group of naturally occurring minerals. The natural zeolites are analcite, chabazite, heulandite, natrolite, stilbite, and thomsonite. Artificial zeolites are made in a variety of forms, ranging from gelatinous to porous and sandlike, and are used as gas adsorbents and drying agents as well as water softeners. Both natural and artificial zeolites are used extensively for water softening. The term zeolite now includes such diverse groups of compounds as sulfonated organics or basic resins, which act in a similar manner to effect either cation or anion exchange.

a generic term for a large group of white or colorless (sometimes tinted red or yellow by impurities) hydrous aluminosilicate minerals that have an open framework structure of interconnected (Si,Al)O4 tetrahedra with exchangeable cations and H O molecules 2in structural cavities. They have a ratio of (Al + Si) to nonhydrous oxygen of 1:2, and are characterized by their easy and reversible loss of water of hydration and by their ready fusion and swelling when strongly heated under the blowpipe. Zeolites have long been known to occur as well formed crystals in cavities in basalt. Of more significance is their occurrence as authigenic minerals in the sediments of saline lades and the deep sea and esp. in beds of tuff. They form “during and after burial, generally by reaction of pore waters with solid aluminosilicate materials (e.g., volcanic glass, feldspar, biogenic silica, and clay minerals).”8

 See footnotes at end of table. (Continued)
NIOSH CIB 62 

• Asbestos 145

Table 1. Definitions of general mineralogical terms (Continued)

Term

Dictionary of Mining, 

Mineral, and Related 

Terms [U.S. Bureau 

of Mines 1996]

[Note: Footnotes identify the Primary Source Citation for the definition]

Glossary of Geology, 5th ed.

[American Geological 

Institute 2005] Leake et al. [1997] NIOSH [1990a]

Zeolite(Continued)

2. A group of hydrous aluminosilicates that are similar to the feldspars. They easily lose and regain their water of hydration and they fuse and swell when heated. Zeolites are frequently used in water softening, ion exchange and absorbent applications.

1Additional definitions can be found in Lowers H, Meeker G [2002]. Tabulation of asbestos-related terminology. Open-file report 02-458 [http://pubs.usgs.gov/of/2002/ofr-02-

458/], pp. 70. Date accessed: December 21, 2009.

2Nelson A [1965]. Dictionary of mining. New York: Philosophical Library, pp. 523.3Pryor EJ [1963]. Dictionary of mineral technology. London: Mining Publications, Ltd., pp. 437.4Mersereau SF [1947]. Materials of industry, 4th ed. New York: McGraw-Hill, pp. 623.5Campbell, WJ et al. Selected silicate minerals and their asbestiform varieties. USBM Circular 8751. Washington, DC: U.S. Department of the Interior, Bureau of Mines.6Chamber’s mineralogical dictionary [1948]. New York: Chemical Publishing Co., pp. 47.7American Geological Institute [1987]. Glossary of geology, 3rd ed. Alexandria, VA; pp. 788. In addition, also by the American Geological Institute: Glossary of geology and related 

sciences [1957], pp. 325; supplement [1969], pp. 72.

8Hay RL [1978]. Geologic occurrence of zeolites. In: Sand LB, Mumpton FA, eds. Natural zeolites. New York: Pergamon, pp. 135–143.
146 NIOSH CIB 62 • Asbestos Table 2. Definitions of specific minerals Term Dictionary of Mining, Mineral, and Related Terms [U.S. Bureau of Mines 1996] [Note: Footnotes identify the Primary Source Citation for the definition] Glossary of Geology, 5th ed. [American Geological Institute 2005] Leake et al. [1997] NIOSH [1990a] Actinolite A monoclinic mineral, 2[Ca2(Fe,Mg)5Si

O8 22(OH)2]; 

in the hornblende series Mg/(Mg+Fe2+) = 0.50 to 0.89 of the amphibole group; forms a series with tremolite; green, bladed, acicular, fibrous (byssolite asbestos), or massive (nephrite jade); prismatic cleavage; in low-grade metamorphic rocks.

A bright-green or grayish-green monoclinic mineral of the amphibole group: Ca2(Fe,Mg)5(OH)2[Si

O8 22]. It may contain 

manganese. It sometimes occurs in the form of asbestos, and also in fibrous, radiated, or columnar forms in metamorphic rocks (such as schists) and in altered igneous rocks. 

A monoclinic calcic amphibole intermediate between ferroactinolite and tremolite: Ca2(Fe,Mg)5Si

O8 22(OH)2; 

with Mg/(Mg+Fe2+) between 

0.5 and 0.9 (otherwise if ≤ 0.5 it is ferroactinolite, and if ≥ 0.9 it is tremolite).

Actinolite can occur in both the asbestiform and nonasbestiform mineral habits and is in the mineral series tremolite-ferroactinolite.1The asbestiform variety is often referred to as actinolite asbestos. 

Amosite 1. A monoclinic mineral in the 

cummingtonite-grunerite series.22. A commercial asbestos composed of asbestiform gedrite, grunerite, or anthophyllite of the amphibole group; has typically long fibers.

A commercial term for an iron-rich, asbestiform variety of amphibole occurring in long fibers. It may consist of an orthorhombic amphibole (anthophyllite or gedrite) or of a monoclinic amphibole (cummingtonite or grunerite).

Amosite is the commercial term derived from the acronym “Asbestos Mines of South Africa.” Amosite is in the mineral series cummingtonite-grunerite,1 in which both asbestiform and nonasbestiform habits of the mineral can occur. This mineral type is commonly referred to as “brown asbestos.”

Antigorite A monoclinic mineral, 

(Mg,Fe)3Si

O2 5(OH)4; kaoliniteserpentine group; polymorphous 

with clinochrysotile, lizardite, orthochrysotile, parachrysotile; greasy variegated green; used as an ornamental stone.

A macroscopically lamellar brown to green monoclinic serpentine mineral, which consists structurally of alternating wave forms in which the 1:1 T-O layer reverses sides and direction of curvature at each wave null point. In most specimens the repeat distance of the wave pattern measures between 25.5 and 51.0 Å: (Mg, Fe2+)3Si

O2 3(OH)4.

 See footnotes at end of table. (Continued)
NIOSH CIB 62 

• Asbestos 147

Table 2. Definitions of specific minerals (Continued)

Term

Dictionary of Mining, 

Mineral, and Related Terms 

[U.S. Bureau of Mines 1996]

[Note: Footnotes identify the Primary Source Citation for the definition]

Glossary of Geology, 5th ed.

[American Geological Institute 2005] Leake et al. [1997] NIOSH [1990a]

Anthophyllite An orthorhombic mineral, 

4[Mg,Fe)7Si O8 22(OH)2]; amphibole group; commonly lamellar or fibrous, green to clove-brown; in schists from metamorphosed ultramafic rocks; a nonspinning grade of asbestos.

A clove-brown to colorless orthorhombic mineral of the amphibole group: (Mg, Fe2+)2(Mg,Fe2+)5Si O8 22(OH)2. It is dimorphous with cummingtonite; with increase in aluminum it grades into gedrite. Anthophyllite occurs in metamorphosed ultrabasic rocks, typically with olivine or talc or in monominerallic aggregates of parallel or radiating asbestiform fibers. It has been mined for asbestos.

An orthorhombic Mg-Fe-MnLi amphibole: Mg7Si O8 22(OH)2; may also contain divalent iron but with Mg/(Mg+Fe2+) ≥ 0.50 (otherwise ferroanthophyllite), and with Si > 7.00 (otherwise it is gedrite).

Anthophyllite can occur in both the asbestiform and nonasbestiform mineral habits. The asbestiform variety is often referred to as anthophyllite asbestos.

Attapulgite A light-green, magnesiumrich clay mineral, named from 

its occurrence at Attapulgus, GA, where it is quarried as fuller’s earth. Crystallizes in the monoclinic system.

palygorskite

Byssolite An olive-green asbestiform 

variety of tremolite-actinolite. 

An olive-green asbestiform variety of tremolite-actinolite.

Clinoptilolite A monoclinic mineral, (Na,

K,Ca) Al 2 3(Al,Si)2Si13O36.12H O; of the zeolite group. 2

A group name for a monoclinic zeolite mineral with the general formula: A2-3(Si,Al)18O36•11H O, where A = Na, K, or Ca. 2

Chrysotile A monoclinic mineral (clinochrysotile), or orthorhombic mineral 

(orthochrysotile, parachrysotile), [Mg6(OH)8Si O4 10]; serpentine group; forms soft, silky white, yellow, green, or gray flexible fibers as veins in altered ultramafic rocks; the chief asbestos minerals. (Not to be confused with chrysolite.)

A white, gray, or greenish orthorhombic or monoclinic mineral of the serpentine group: Mg3(OH)4Si O2 5. It is a highly fibrous, silky variety of serpentine, and constitutes the most important type of asbestos. Not to be confused chrysolite.

Chrysotile generally occurs segregated as parallel fibers in veins or veinlets and can easily separate into individual fibers or bundles. Often referred to as “white asbestos,” it is used commercially for its good spinnability in the making of textile products, and as an additive in cement’ or friction products.

 See footnotes at end of table. (Continued)
148 NIOSH CIB 62 

• Asbestos

Table 2. Definitions of specific minerals (Continued)

Term

Dictionary of Mining, 

Mineral, and Related Terms 

[U.S. Bureau of Mines 1996]

[Note: Footnotes identify the Primary Source Citation for the definition]

Glossary of Geology, 5th ed.

[American Geological Institute 2005] Leake et al. [1997] NIOSH [1990a]

Crocidolite An asbestiform variety of 

riebeckite; forms lavender-blue, or indigo-blue, or leek-green silky fibers and massive and earthy forms; suited for spinning and weaving. Also spelled krokitolit.

An asbestiform variety of riebeckite; forms lavender-blue, or indigo-blue, or leek-green silky fibers and massive and earthy forms. Also spelled krokidolit.

Crocidolite is from the fibrous habit of the mineral riebeckite and is in the mineral series glaucophane-riebeckite, in which both asbestiform and nonasbestiform habits can occur. This mineral type is commonly referred to as “blue asbestos.” 

Cummingtonite A monoclinic mineral, 

(Fe,Mg)7Si O8 22(OH)2; amphibole group; has Mg/(Mg+Fe2+) = 0.30 to 0.69; prismatic cleavage; may be asbestiform; in amphibolites and dacites; fibrous varieties (amosite, magnesium rich, and montasite, iron rich) are used as asbestos.

A dark green, brown, gray, or beige monoclinic member of the amphibole group: (Mg,Fe2+)7Si O8 22(OH)2. It is dimorphous with anthophyllite, and typically contains calcium and manganese. Cummingtonite occurs in metamorphosed ironstone, mafic and ultrabasic rocks, some dacites and rhyolites, and as a component of uralite. Its iron-rich variety is grunerite.

A monoclinic Mg-Fe-Mn-Li amphibole: Mg7Si O8 22(OH)2; may also contain divalent iron but with Mg/(Mg+Fe2+) ≥ 0.50 (otherwise it is grunerite)

Erionite A white hexagonal zeolite mineral. [Ed. Note: 

Designated as Erionite (Ca,K,Na) depending on the dominant cation substitution.

Ferroactinolite A monoclinic mineral, 

Ca2(Fe2+,Mg)5Si O8 22(OH)2]; amphibole group; has Mg/(Mg+Fe2+) = 0 to 0.50; forms a series with tremolite and actinolite. Formerly called ferrotremolite.

A green-black monoclinic mineral component representing a theoretical end-member of the amphibole group: Ca2Fe2+5Si O8 22(OH)2. Syn: ferrotremolite.

A monoclinic calcic amphibole: Ca2Fe2+5Si O8 22(OH)2; may also contain magnesium but with Mg/(Mg+Fe2+) ≤ 0.5 (otherwise it is actinolite).

 See footnotes at end of table. (Continued)
NIOSH CIB 62 

• Asbestos 149

Table 2. Definitions of specific minerals (Continued)

Term

Dictionary of Mining, 

Mineral, and Related Terms 

[U.S. Bureau of Mines 1996]

[Note: Footnotes identify the Primary Source Citation for the definition]

Glossary of Geology, 5th ed.

[American Geological Institute 2005] Leake et al. [1997] NIOSH [1990a]

Fluoro-edenite A vitreous dark brown monoclinic 

mineral of the amphibole group: (Na,K)Ca2(Mg,Fe2+)5(Si Al)O 7 22(F,OH). It represents edenite with F>OH.

Grunerite A monoclinic mineral, 

(Fe,Mg)7Si O8 22(OH)2; amphibole group; with Mg/(Mg+Fe2+) = 0-0.30; forms series with cummingtonite and magnesiocummingtonite; fibrous or needlelike, commonly in radial aggregates; characteristic of iron formations in the Lake Superior and Labrador Trough regions. Also spelled gruenerite.

A monoclinic Mg-Fe-Mn-Li amphibole: Fe2+7Si O8 22(OH)2; may also contain magnesium but with Mg/(Mg+Fe2+) < 0.50 

(otherwise it is cummingtonite).

Halloysite 1. A monoclinic mineral, 

2[Al4Si4(OH) O8 10]; kaoliniteserpentine group; made up of slender tubes as shown by electron microscopy; a gangue mineral in veins.

A 1:1 aluminosilicate clay mineral Al2Si O2 5(OH)4•X(H O) similar to kaolinite 2but perhaps with some Al(IV) and interlayer cations to compensate for the Al(IV). Probably because of this it is able to incorporate water in the interlayer space [Bailey 1989]. The terms “halloysite (7Å)” and halloysite (10Å)” were recommended for the anhydrous and dihydrate forms, respectively [Brindley and Pegro 1976]3; the term “endellite” should not be used [Bailey et al. 1980].4

2. Used as a group name to include natural “halloysite minerals” with different levels of hydration, as well as those formed artificially.

 See footnotes at end of table. (Continued)
150 NIOSH CIB 62 

• Asbestos

Table 2. Definitions of specific minerals (Continued)

Term

Dictionary of Mining, 

Mineral, and Related Terms 

[U.S. Bureau of Mines 1996]

[Note: Footnotes identify the Primary Source Citation for the definition]

Glossary of Geology, 5th ed.

[American Geological Institute 2005] Leake et al. [1997] NIOSH [1990a]

Lizardite A trigonal and hexagonal mineral, 

Mg3Si O2 5(OH)4; kaolinite-serpentine group; polymorphous with antigorite, clinochrysotile, orthochrysotile, and parachrysotile; forms a series with nepouite; in platy masses as an alteration product of ultramafic rocks; the most abundant serpentine mineral.

The most abundant form of the trioctahedral serpentine minerals. It crystallizes as flat platelets. Variable amounts of Al substitute for both Mg and Si in the ideal serpentine formula of Mg3Si O2 5(OH)4 to create a better lateral fit between the component octahedral and tetrahedral sheets than found in antigorite and chrysotile. Several polytypes exist: rhombohedral, trigonal, hexagonal, or monoclinic.

Mordenite A white, yellowish, or pinkish 

member of the zeolite group of minerals with the formula (Ca,Na K2 2)Al2Si10O24.7H O. 2

A white, yellowish, or pinkish orthorhombic zeolite mineral: (Na2,Ca,K2)Al2Si10O24•7H O. 2

Palygorskite 1. A monoclinic and 

orthorhombic mineral, (OH)2(Mg,Al)4(Si,Al) O8 20•8H O; 2fibrous; in desert soils.2. A general name for lightweight fibrous clay minerals showing significant substitution of aluminum for magnesium; characterized by distinctive rodlike shapes under an electron microscope.

(a) A white, grayish, yellowish, or grayish-green chain-structure clay mineral: (Mg,Al)2Si O4 10(OH)•4H O. 2It crystallizes in several monoclinic and orthorhombic polytypes. (b) A group name for monoclinic minerals with an analogous composition, but with Mg replaced by Mn or Na, and AL replaced by Fe3+ or Mn3+.

 See footnotes at end of table. (Continued)
NIOSH CIB 62 

• Asbestos 151

Table 2. Definitions of specific minerals (Continued)

Term

Dictionary of Mining, 

Mineral, and Related Terms 

[U.S. Bureau of Mines 1996]

[Note: Footnotes identify the Primary Source Citation for the definition]

Glossary of Geology, 5th ed.

[American Geological Institute 2005] Leake et al. [1997] NIOSH [1990a]

Phillipsite A monoclinic mineral, (K,Na,Ca)1-

2(Si,Al) O8 16.6H O; zeolite group; 2commonly occurs in complex twinned crystals; in basalt amydules, in pelagic red clays, in palagonite tuffs, in alkaline saline lakes from silicic vitric volcanic ash, in alkaline soils, and around hot springs in Roman baths.

A colorless or white monoclinic zeolite mineral. Usually designated as phillipsite – (Ca, K, or Na) depending on which is the dominant exchangeable cation, (Ca,K,Na)2(Si,Al) O8 16•6H O. 2

Richterite A brown, yellow, or rose-red monoclinic 

member of the amphibole group: Na CaMg 2 5Si O8 22(OH)2. Cf: soda tremolite

A monoclinic sodic-calcic amphibole: Na(CaNa)Mg5Si O8 22(OH)2; may also contain divalent iron but with Mg/(Mg+Fe2+) ≥ 0.5 (otherwise it is ferrorichterite)

Riebeckite A monoclinic mineral, Na Ca 2

(Mg,Fe2+)5Si O8 22(OH)2 [sic]; amphibole group with Mg/(Mg+Fe2+) = 0 to 0.49 and Fe3+/(Fe3++Al) = 0.7 to 1.0; forms a series with magnesioriebeckite; fibrous; in soda-rich rhyolites, granites, and pegmatites; crocidolite variety is blue asbestos; tiger eye is crocidolite replaced by quartz.

A dark blue or black monoclinic mineral of the amphibole group: Na2Fe2+3Fe3+2Si O8 22(OH)2. It occurs as a primary constituent in some acid or sodium-rich igneous rocks. See also: crocidolite

A monoclinic sodic amphibole: Na2(Fe2+3Fe3+2)Si O8 22(OH)2; 

may also contain aluminum in place of trivalent iron but with VIAl < Fe3+ otherwise it is 

ferroglaucophane, and may also contain sodium and potassium in the A position but with 

(Na+K)A < 0.50 otherwise it is arfvedsonite, and may also contain magnesium in place of divalent iron but with Mg/(Mg+Fe2+) < 0.5 otherwise it is magnesioriebeckite

 See footnotes at end of table. (Continued)
152 NIOSH CIB 62 

• Asbestos

Table 2. Definitions of specific minerals (Continued)

Term

Dictionary of Mining, 

Mineral, and Related Terms 

[U.S. Bureau of Mines 1996]

[Note: Footnotes identify the Primary Source Citation for the definition]

Glossary of Geology, 5th ed.

[American Geological Institute 2005] Leake et al. [1997] NIOSH [1990a]

Sepiolite A monoclinic mineral, 

Mg4Si O6 15(OH)2.6H O; soft; sp 2gr, 2, but fibrous dry masses float on water; occurs in veins in calcite and in alluvial deposits formed from weathering of serpentine masses, chiefly in Asia Minor, as meerschaum; may be used in making pipes, ornamental carvings.

An orthorhombic chain-structure clay mineral: Mg4Si O6 15(OH)2•6H O. It is a white to 2light gray or light yellow material, extremely lightweight, absorbent, and compact, that is found chiefly in Asia Minor and is used for making tobacco pipes, cigar and cigarette holders and ornamental carvings. Sepiolite occurs in veins with calcite, and in alluvial deposits formed from weathering of serpentine masses.

Tremolite A monoclinic mineral, 

2[Ca Mg 2 5Si O8 22(OH)2]; amphibole group with magnesium replaced by iron, and silicon by aluminum toward actinolite; white to green, long-bladed or stout prismatic crystals, may show columnar, fibrous, or granular masses or compact aggregates; in low-grade metamorphic rocks such as dolomitic limestones and talc schists; the nephrite variety is the gemstone jade; the asbestiform variety is byssolite.

A white to dark-gray monoclinic mineral of the amphibole group: Ca Mg 2 5Si O8 22(OH)2. It has varying amounts of iron, and may contain manganese and chromium. Tremolite occurs in long blade-shaped or short stout prismatic crystals and also in columnar, fibrous, or granular masses or compact aggregates, generally in metamorphic rocks such as crystalline dolomitic limestones and talc schists. It is a constituent of much commercial talc.

A monoclinic calcic amphibole: Ca Mg 2 5Si O8 22(OH)2; may also contain divalent iron but with Mg/(Mg+Fe2+) ≥0.9 (otherwise it is actinolite)

Tremolite can occur in both the asbestiform and nonasbestiform mineral habits and is in the mineral series tremoliteferroactinolite.1 The asbestiform variety is often referred to as tremolite asbestos.

Winchite A blue or gray monoclinic member of the 

amphibole group: NaCa(Mg Al)Si 4 O8 22(OH)2

A monoclinic sodic-calcic amphibole: (CaNa)Mg4(Al,Fe3+)Si O8 22(OH)2; may also contain 

divalent iron but with Mg/(Mg+Fe2+) ≥ 0.5 (otherwise it is ferrorichterite)

 See footnotes at end of table. (Continued)
NIOSH CIB 62 

• Asbestos 153

Table 2. Definitions of specific minerals (Continued)

Term

Dictionary of Mining, 

Mineral, and Related Terms 

[U.S. Bureau of Mines 1996]

[Note: Footnotes identify the Primary Source Citation for the definition]

Glossary of Geology, 5th ed.

[American Geological Institute 2005] Leake et al. [1997] NIOSH [1990a]

Wollastonite A triclinic mineral of the pyroxenoid group: CaSiO3. It is dimorphous with parawollastonite. 

Wollastonite is found in contactmetamorphosed limestones, and occurs usually in cleavable masses or sometimes in tabular twinned crystals; it may be white, gray, brown, red, or yellow. It is not a pyroxene. Symbol, Wo.

A triclinic or monoclinic chain silicate mineral of the pyroxenoid type: CaSiO3. It [in the original source, a word is missing here.] dimorphous with parawollastonite. Wollastonite is found in contactmetamorphosed limestones, and occurs usually in cleavable masses or sometimes in tabular twinned crystals; it may be white, gray, brown, red, or yellow. It is not a pyroxene. Several polytypes have been characterized. Symbol: Wo.

1Mineral series such as cummingtonite-grunerite and tremolite-ferroactinolite are created when one cation is replaced by another in a crystal structure without significantly altering the structure. There may be a gradation in the structure in some series, and minor changes in physical characteristics may occur with elemental substitution. Usually a series 

has two end members with an intermediate substitutional compound being separately named, or just qualified by being referred to as members of the series. Members of the tremolite-ferroactinolite series are hydroxylated calcium-magnesium, magnesium-iron, and iron silicates, with the intermediate member of this series being named actinolite.

2Sinclair WE [1959]. Asbestos: its origin, production and utilization. Mining, 2nd ed. London: Publications, Ltd. pp. 512.3Brindley GW, Pedro G [1976]. Meeting of the nomenclature committee of AIPEA; Mexico City, July 12, 1975. AIPEA Newsletter 12:5–6.4The original source does not provide the full reference for this citation.
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