Health Effects of Occupational Exposure
to Respirable Crystalline Silica

Department of Health and Human Services
Centers for Disease Control and Prevention
National Institute for Occupational Safety and Health

DHHS (NIOSH) Publication No. 2002-129
April 2002

Contents

Ordering Information
Foreword
Abstract
Executive Summary
Abbreviations
Glossary
Acknowledgments

1 Introduction

1.1 Definition of Crystalline Silica
1.2 Current Health Issues
1.3 History of NIOSH Activity
1.4 Purpose and Scope

2 Properties, Production, and Potential for Exposure

2.1 Chemical and Physical Properties
2.2 Number of Workers Potentially Exposed
2.3 Dust-Generating Activities, Uses, and Potential Exposures
2.4 Sampling and Analytical Methods

2.4.1 Sampling Methods
2.4.2 Analytical Methods

2.4.2.1 XRD Spectrometry
2.4.2.2 IR Spectrometry
2.4.2.3 Colorimetric Spectrophotometry
2.4.2.4 Factors Affecting the Sensitivity and Accuracy of Analytical Techniques

2.4.3 Feasibility of Measuring Crystalline Silica at Various Concentrations

3 Human Health Effects

3.1 Epidemiologic Considerations in Occupational Respiratory Disease Studies

3.1.1 Study Designs
3.1.2 Sources of Bias

3.2 Silicosis

3.2.1 Definition
3.2.2 Epidemiologic Exposure-Response Models of Silicosis

3.3 TB and Other Infections

3.3.1 Definition
3.3.2 Epidemiologic Studies

3.4 Cancer

3.4.1 Background
3.4.2 Epidemiologic Studies of Lung Cancer

3.4.2.1 Updated or New Studies Since the IARC Review
3.4.2.2 Lung Cancer Meta-Analyses

3.4.3 Other Cancers

3.5 Other Nonmalignant Respiratory Diseases and Related Conditions

3.5.1 COPD

3.5.1.1 Definition
3.5.1.2 Epidemiologic Studies

3.5.2 Asthma
3.5.3 Chronic Bronchitis

3.5.3.1 Definition
3.5.3.2 Epidemiologic Studies

3.5.4 Abnormalities in Pulmonary Function Tests

3.5.4.1 Definition
3.5.4.2 Epidemiologic Studies Quantitative Estimates of Dust-Related Loss of Lung Function

3.5.5 Emphysema

3.5.5.1 Definition
3.5.5.2 Epidemiologic Studies

3.5.6 Nonmalignant Respiratory Disease (NMRD) Mortality

3.6 Autoimmune and Chronic Renal Diseases
3.7 Other Health Effects

4 Experimental Studies

4.1 Biomarkers
4.2 Cytotoxicity
4.3 Genotoxicity and Related Effects
4.4 Carcinogenicity

5 Conclusions

5.1 Lung Cancer
5.2 Noncarcinogenic Health Effects
5.3 Exposures, Monitoring, and Controls

6 Research Needs

6.1 Health-Related Research
6.2 Research Related to Exposure Measurement
6.3 Research Related to the Control of Exposure

References

Appendix. Occupational Exposure Limits

Tables

1. Nonmining and mining industries with the largest numbers of U.S. workers potentially exposed to respirable crystalline silica, 1986
2. Main industries and activities around the world in which
silica exposure has been reported
3. Industrial silica sand and gravel sold or used
by U.S. producers in 1994, by major end use
4. Most frequently recorded occupations of U.S. residents aged 15 or above whose death certificates list silicosis as an underlying or contributory cause of death—selected States, 1991–1992
5. Other occupations reporting cases of silicosis in workers
6. XRD sampling and analytical methods for crystalline silica
7. IR sampling and analytical methods for crystalline silica
8. Intralaboratory results for evaluation of XRD silica method
9. Intralaboratory results for evaluation of IR silica method
10. XRD method evaluation: concentration ranges bracketing applicable exposure limits for which the NIOSH accuracy criterion is met ( µg/m³)
11. IR method: concentration ranges bracketing applicable exposure limits for which the NIOSH accuracy criterion is met (µg/m³)
12. Predicted incidence or prevalence of silicosis following exposure to selected concentrations of respirable quartz dust—based on modeling of cumulative exposure over a 45-year working lifetime
13. Summary of epidemiologic studies of silicosis with cumulative dust exposure data and silicosis risk estimates
14. Selected age-adjusted PMRs*,† for pulmonary TB by usual occupation, sex, and race in 28 States, 1979–1990
15. IARC*-reviewed epidemiologic studies having the least confounded investigations of an association between occupational exposure to crystalline silica and lung cancer
16. Epidemiologic studies of bronchitis in workers exposed to silica dust
17. Loss of lung function (FEV₁)* associated with cumulative exposure to respirable granite dust
18. Epidemiologic studies of emphysema in workers exposed to silica dust
19. Epidemiologic studies of immunologic, autoimmune, and chronic renal disease (including subclinical renal changes) in silica-exposed workers
20. Molecular epidemiology studies of biomarkers for carcinogenesis or silicosis
21. Summary of the genotoxic effects of quartz in mammalian cells
22. Summary of data on lung tumors induced in rats by crystalline silica
23. Lung tumors induced in Fischer 344 rats by a single intratracheal instillation of quartz
A-1. U.S. guidelines and limits for occupational exposure to crystalline silica

Ordering Information

To receive documents or more information about occupational safety and health topics, contact the National Institute for Occupational Safety and Health (NIOSH) at

NIOSH Publications Dissemination
4676 Columbia Parkway
Cincinnati, OH 45226-1998

Telephone: 1-800-35-NIOSH (1-800-356-4674)
Fax: 1-513-533-8573
E-mail: pubstaft@cdc.gov

or visit the NIOSH Web site at www.cdc.gov/niosh

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 NIOSH.

DHHS (NIOSH) Publication No. 2002-129

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Foreword

Silicosis is the disease most associated with crystalline silica exposure; it is incurable but preventable. This debilitating and often fatal lung disease persists worldwide despite long-standing knowledge of its cause and methods for controlling it.

This Hazard Review, Health Effects of Occupational Exposure to Respirable Crystalline Silica, describes published studies and literature on the health effects of occupational exposure to respirable crystalline silica among workers in the United States and many other countries. The review indicates a significant risk of chronic silicosis for workers exposed to respirable crystalline silica over a working lifetime at the current Occupational Safety and Health Administration (OSHA) permissible exposure limit (PEL), the Mine Safety and Health Administration (MSHA) PEL, or the National Institute for Occupational Safety and Health (NIOSH) recommended exposure limit (REL). In addition to the risk of silicosis, epidemiologic studies indicate that workers exposed to respirable crystalline silica have an increased risk of developing lung cancer, pulmonary tuberculosis, and airways diseases. The latest scientific information also indicates possible associations of occupational exposure to silica dust with various other adverse health effects.

Until improved sampling and analytical methods are developed for respirable crystalline silica, NIOSH will continue to recommend an exposure limit of 0.05 mg/m³ as a time-weighted average (TWA) for up to a 10-hr workday during a 40-hr workweek. NIOSH also recommends substituting less hazardous materials for crystalline silica when feasible, using appropriate respiratory protection when source controls cannot keep exposures below the REL, and making medical examinations available to exposed workers.

Kathleen M. Rest, Ph.D., M.P.A.
Acting Director, National Institute for
Occupational Safety and Health
Centers for Disease Control and Prevention

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Abstract

Occupational exposures to respirable crystalline silica are associated with the development of silicosis, lung cancer, pulmonary tuberculosis, and airways diseases. These exposures may also be related to the development of autoimmune disorders, chronic renal disease, and other adverse health effects. Recent epidemiologic studies demonstrate that workers have a significant risk of developing chronic silicosis when they are exposed to respirable crystalline silica over a working lifetime at the current Occupational Safety and Health Administration (OSHA) permissible exposure limit (PEL), the Mine Safety and Health Administration (MSHA) PEL, or the National Institute for Occupational Safety and Health (NIOSH) recommended exposure limit (REL).

This NIOSH Hazard Review

1. examines the health risks and diseases associated with occupational exposures to respirable crystalline silica,
2. discusses important findings of recent epidemiologic studies,
3. provides the reader with sources of more comprehensive information about health effects and experimental studies
4. describes current sampling and analytical methods and their limitations for assessing occupational exposures to respirable crystalline silica, and
5. suggests many areas for further research.

Current sampling and analytical methods used to evaluate occupational exposure to respirable crystalline silica do not meet the accuracy criterion needed to quantify exposures at concentrations below the NIOSH REL of 0.05 mg/m³ as a time-weighted average (TWA) for up to a 10-hr workday during a 40-hr workweek. Until improved sampling and analytical methods are developed for respirable crystalline silica, NIOSH will continue to recommend an exposure limit of 0.05 mg/m³ to reduce the risk of developing silicosis, lung cancer, and other adverse health effects. NIOSH also recommends minimizing the risk of illness that remains for workers exposed at the REL by substituting less hazardous materials for crystalline silica when feasible, by using appropriate respiratory protection when source controls cannot keep exposures below the NIOSH REL, and by making medical examinations available to exposed workers.

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Executive Summary

Occupational exposures to respirable crystalline silica occur in a variety of industries and occupations because of its extremely common natural occurrence and the wide uses of materials and products that contain it. At least 1.7 million U.S. workers are potentially exposed to respirable crystalline silica [NIOSH 1991], and many are exposed to concentrations that exceed limits defined by current regulations and standards.

Silicosis, usually a nodular pulmonary fibrosis, is the disease most associated with exposure to respirable crystalline silica. Although the reported mortality associated with silicosis has declined over the past several decades, many silicosis associated deaths still occur (nearly 300 deaths were reported each year during the period 1992-1995) [NIOSH 1996a; Althouse 1998]. In addition, the number of silicosis associated deaths among persons aged 15 to 44 has not declined substantially [CDC 1998a,b]. An unknown number of workers also continue to die from silica-related diseases such as pulmonary tuberculosis (TB), lung cancer, and scleroderma. The number of cases of silicosis and silica-related diseases in the United States today is unknown.

Symptoms of acute silicosis, another form of silicosis, may develop shortly after exposure to high concentrations of respirable crystalline silica. Epidemiologic studies focus on chronic silicosis, which develops years after exposure to relatively low concentrations of respirable crystalline silica. Epidemiologic studies have found that chronic silicosis may develop or progress even after occupational exposure has ceased [Hessel et al. 1988; Hnizdo and Sluis-Cremer 1993; Hnizdo and Murray 1998; Ng et al. 1987; Kreiss and Zhen 1996; Miller et al. 1998]. Over a 40- or 45-year working lifetime, workers have a significant chance (at least 1 in 100) of developing radiographic silicosis when exposed to respirable crystalline silica at the Occupational Safety and Health Administration (OSHA) permissible exposure limit (PEL), the Mine Safety and Health Administration (MSHA) PEL, or the National Institute for Occupational Safety and Health (NIOSH) recommended exposure limit (REL).*

Silicosis may be complicated by severe mycobacterial or fungal infections. About half of these are caused by Mycobacterium tuberculosis and result in TB. Epidemiologic studies have firmly established that silicosis is a risk factor for developing TB.

*See appendix for the OSHA and MSHA PELs. The NIOSH REL is 0.05 mg/m³
as a time-weighted average (TWA) for up to a 10-hr workday during a 40-hr workweek.

The carcinogenicity of crystalline silica in humans has been strongly debated in the scientific community. In 1996, the International Agency for Research on Cancer (IARC) reviewed the published experimental and epidemiologic studies of cancer in animals and workers exposed to respirable crystalline silica and concluded that there was sufficient evidence in humans for the carcinogenicity of inhaled crystalline silica in the form of quartz or cristobalite from occupational sources [IARC 1997]. In the same year, directors of the American Thoracic Society (ATS) adopted an official statement that described the adverse health effects of exposure to crystalline silica, including lung cancer [ATS 1997]. The ATS found that “the available data support the conclusion that silicosis produces increased risk for bronchogenic carcinoma.”

However, the ATS noted that less information was available for lung cancer risks among silicotics who had never smoked and for silica-exposed workers who did not have silicosis. They also stated that it was less clear whether silica exposure was associated with lung cancer in the absence of silicosis. NIOSH has reviewed the studies considered by IARC and ATS, and NIOSH concurs with the conclusions of IARC [1997] and the ATS [1997]. These conclusions agree with NIOSH testimony to OSHA, in which NIOSH recommended that crystalline silica be considered a potential occupational carcinogen [54 Fed. Reg.* 2521 (1989)]. Further research is needed to determine the exposure-response relationship between lung cancer in nonsmokers and occupational silica dust exposure and to determine why lung cancer risks appear to be higher in workers with silicosis. The cellular mechanisms for development of lung cancer after crystalline silica exposure have been explored in many experimental studies and are not yet fully understood.

Statistically significant excesses of mortality from stomach or gastric cancer have been reported in various occupational groups exposed to crystalline silica. However, no conclusion about an association has been reached because most studies did not adjust for the effects of confounding factors or assess an exposure-response relationship for crystalline silica. The same problem exists for the infrequent reports of statistically significant numbers of excess deaths or cases of other nonlung cancers in silica-exposed workers.

Occupational exposure to respirable crystalline silica is associated with chronic obstructive pulmonary disease, including bronchitis and emphysema. The results of some epidemiologic studies suggest that these diseases may be less frequent or absent in nonsmokers. Exposure to respirable crystalline silica is not associated with asthma.

*Federal Register. See Fed. Reg. in references.

Significant increases in mortality from nonmalignant respiratory disease (a broad category that can include silicosis and other pneumoconioses, chronic bronchitis, emphysema, asthma, and other related respiratory conditions) have been reported for silica-exposed workers [Checkoway et al. 1997, 1993; Chen et al. 1992; Cherry et al. 1998; Brown et al. 1986; Costello and Graham 1988; Costello et al. 1995; Costello 1983; Steenland and Brown 1995b; Steenland and Beaumont 1986; Thomas and Stewart 1987; Thomas 1990] and silicotics [Goldsmith et al. 1995; Brown et al. 1997; Rosenman et al. 1995].

Many case reports have been published about autoimmune diseases or autoimmune-related diseases in workers exposed to crystalline silica or workers with silicosis. In addition, several recent epidemiologic studies reported statistically significant numbers of excess cases or deaths from known autoimmune diseases or immunologic disorders (scleroderma, systemic lupus erythematosus, rheumatoid arthritis, sarcoidosis), chronic renal disease, and subclinical renal changes. The pathogenesis of autoimmune and renal diseases in silica-exposed workers is not clear.

Various other health effects (such as hepatic or hepatosplenic silicosis, extrapulmonary deposition of silica particles, liver granulomas, hepatic porphyria, cutaneous silica granulomas, pulmonary alveolar proteinosis, podoconiosis, and dental abrasion) have been reported in studies of silica-exposed workers, but these effects have not been studied in depth with epidemiologic methods.

This Hazard Review also provides an abbreviated review of experimental research studies conducted to identify the molecular mechanisms responsible for the development of silicosis and lung cancer. The results of these studies indicate the need for

1. additional long-term carcinogenesis studies in animals to determine dose-response relationships and
2. in vivo and in vitro studies to develop effective cellular and molecular models of carcinogenesis.

Although a large body of published literature describes the health effects of crystalline silica, some areas require further research. Many uncertainties exist, including

1. mechanisms and the influence of particle characteristics on development of disease;
2. toxicity and pathogenicity of nonquartz crystalline silica, silica substitutes, and dust mixtures;
3. translocation of particles from the lung; and
4. dose/exposure-response relationships in animals and in humans.

In addition, further information is needed about

1. methods for reducing dust exposures in a wide variety of industries and the feasibility of implementing such methods,
2. methods for effectively communicating to workers the dangers of inhaling silica dust and the importance of using appropriate control technologies and other protective measures, and
3. exposure sampling and analytical methods that will allow quantification of crystalline silica at low airborne concentrations (currently these techniques do not meet the accuracy criterion needed to quantify exposures at concentrations below the NIOSH REL).

Until improved sampling and analytical methods are developed for respirable crystalline silica, NIOSH will continue to recommend an exposure limit of 0.05 mg/m³ to reduce the risk of developing silicosis, lung cancer, and other adverse health effects. NIOSH also recommends minimizing the risk of illness that remains for workers exposed at the REL by substituting less hazardous materials for crystalline silica when feasible, by using appropriate respiratory protection when source controls cannot keep exposures below the NIOSH REL, and by making medical examinations available to exposed workers.

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Acknowledgments

This Hazard Review was developed by the staff of the National Institute for Occupational Safety and Health (NIOSH). Paul A. Schulte, Director, Education and Information Division (EID), had overall responsibility for the document. Faye L. Rice (EID) was the principal author. The analytical methods section was prepared by Rosa Key-Schwartz, Ph.D.; David Bartley, Ph.D; Paul Baron, Ph.D; and Paul Schlecht. Michael Gressel and Alan Echt contributed material on control technology.

The following NIOSH staff provided critical review and comments on this document and previous versions: Martin Abell; Heinz W. Ahlers, J.D.; Rochelle Althouse; Harlan Amandus, Ph.D.; Michael Attfield, Ph.D.; Nancy Bollinger, Ph.D.; Lorraine Cameron, Ph.D.; Robert Castellan, M.D.; Joseph Cocalis; Joseph Costello; Clayton Doak; Jerome Flesch; Bryan Hardin, Ph.D.; Kent Hatfield, Ph.D.; Frank Hearl; Paul Hewett, Ph.D.; Eva Hnizdo, Ph.D. (formerly of the National Centre for Occupational Health, South Africa); Michael Jacobsen, Ph.D. (visiting scientist); Kathleen Kreiss, M.D.; Kenneth Linch; Charles Lorberau; Tong-man Ong, Ph.D.; John Parker, M.D.; Larry Reed; Karl Sieber, Ph.D.; Rosemary Sokas, M.D.; Leslie Stayner, Ph.D.; Kyle Steenland, Ph.D.; Patricia Sullivan, Sc.D.; Marie Haring Sweeney, Ph.D.; Gregory Wagner, M.D.; William Wallace, Ph.D.; Joann Wess; Ralph Zumwalde.

Editorial review and camera-copy production were provided by Vanessa L. Becks, Susan E. Feldmann, Joyce D. Godfrey, Anne C. Hamilton, Susan R. Kaelin, Laura A. Stroup, Kristina M. Wasmund, and Jane B. Weber. Dale Camper and Ronald Schuler performed literature searches, and the EID Library staff collected literature used in the development of the document.

NIOSH also appreciates the comments of the following external reviewers:

William Beckett, M.D., M.P.H.
University of Rochester School of Medicine
P.O. Box EHSC
575 Elmwood Avenue
Rochester, NY 14642

Harvey Checkoway, Ph.D.
Department of Environmental Health
University of Washington
Box 357234
Seattle, WA 981957234

Gerald S. Davis, M.D.
University of Vermont College of Medicine
Pulmonary Unit
Given C317
Burlington, VT 05405

Jeffrey Gift, Ph.D.
Senior Health Scientist
U.S. Environmental Protection Agency
NCEA-RTP Maildrop 52
Research Triangle Park, NC 27711

David Goldsmith, Ph.D.
Department of Environmental and
Occupational Health
George Washington University
2300 K Street, N.W., Suite 201
Washington, DC 20037

Eva Hnizdo, Ph.D.
Epidemiology and Surveillance Section
National Centre for Occupational Health
P.O. Box 4788
Johannesburg 2000, South Africa

Janet Hughes, Ph.D.
Department of Biostatistics
and Epidemiology
Tulane School of Public Health
and Tropical Medicine
1430 Tulane Avenue
New Orleans, LA 70112

Carol Jones, Ph.D.
Senior Health Specialist
Mine Safety and Health Administration
4015 Wilson Boulevard, Room 622
Arlington, VA 22203

William Kojola
American Federation of Labor and
Congress of Industrial Organizations
Department of Occupational Safety and Health
815 Sixteenth Street, N.W.
Washington, DC 20006

Allen G. Macneski
Manager, Environmental Safety and Health
Bechtel National, Inc.
151 Lafayette Drive
Oak Ridge, TN 37830

Michelle Schaper, Ph.D.
Toxicologist
Directorate of Technical Support
Mine Safety and Health Administration
4015 Wilson Boulevard, Room 622
Arlington, VA 22203

Loretta Schuman, Ph.D.
Directorate of Health Standards Program
Occupational Safety and Health Administration
200 Constitution Avenue, N.W., Room N3718
Washington, DC 20210

James Sharpe
Director of Safety and Health Services
National Stone Association
1415 Elliot Place, N.W.
Washington, DC 200072599

David M. Tucker
Manager, Industrial Hygiene
Norfolk Southern Corporation
Environmental Protection
110 Franklin Road, S.E.
Box 13
Roanoke, VA 240420013

John A. Ulizio
Vice President
U.S. Silica Company
P.O. Box 187
Berkeley Springs, WV 25411

James L. Weeks, Sc.D.
George Washington University Medical Center
Division of Occupational and
Environmental Medicine
2300 K Street, N.W., Suite 201
Washington, DC 20037

References and information were submitted by William G.B. Graham, M.D., University of Vermont, College of Medicine. The author especially thanks David Goldsmith, Ph.D., for his major contribution and efforts on a previous draft.

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