TOXICOLOGICAL PROFILE FOR 

SYNTHETIC VITREOUS FIBERS 

U.S. DEPARTMENT OF HEALTH AND HUMAN SERVICES 

Public Health Service 

Agency for Toxic Substances and Disease Registry
 

September 2004 
SYNTHETIC VITREOUS FIBERS ii 

DISCLAIMER 

The use of company or product name(s) is for identification only and does not imply endorsement by the 

Agency for Toxic Substances and Disease Registry. 
SYNTHETIC VITREOUS FIBERS iii 

UPDATE STATEMENT 

A Toxicological Profile for Synthetic Vitreous Fibers, Draft for Public Comment was released in 

September 2002. This edition supersedes any previously released draft or final profile. 

Toxicological profiles are revised and republished as necessary. For information regarding the update 

status of previously released profiles, contact ATSDR at: 

Agency for Toxic Substances and Disease Registry
 

Division of Toxicology/Toxicology Information Branch 

1600 Clifton Road NE, 

Mailstop F-32 

Atlanta, Georgia 30333 



 

 

SYNTHETIC VITREOUS FIBERS vii 

QUICK REFERENCE FOR HEALTH CARE PROVIDERS 

Toxicological Profiles are a unique compilation of toxicological information on a given hazardous 

substance. Each profile reflects a comprehensive and extensive evaluation, summary, and interpretation 

of available toxicologic and epidemiologic information on a substance. Health care providers treating 

patients potentially exposed to hazardous substances will find the following information helpful for fast 

answers to often-asked questions. 

Primary Chapters/Sections of Interest 

Chapter 1: Public Health Statement: The Public Health Statement can be a useful tool for educating 

patients about possible exposure to a hazardous substance. It explains a substance’s relevant toxicologic 

properties in a nontechnical, question-and-answer format, and it includes a review of the general health 

effects observed following exposure. 

Chapter 2: Relevance to Public Health: The Relevance to Public Health Section evaluates, interprets, 

and assesses the significance of toxicity data to human health. 

Chapter 3: Health Effects: Specific health effects of a given hazardous compound are reported by type 

of health effect (death, systemic, immunologic, reproductive), by route of exposure, and by length of 

exposure (acute, intermediate, and chronic). In addition, both human and animal studies are reported in 

this section. 

NOTE: Not all health effects reported in this section are necessarily observed in the clinical 

setting. Please refer to the Public Health Statement to identify general health effects observed 

following exposure. 

Pediatrics: Four new sections have been added to each Toxicological Profile to address child health 

issues: 

Section 1.6 How Can (Chemical X) Affect Children? 

Section 1.7 How Can Families Reduce the Risk of Exposure to (Chemical X)? 

Section 3.7 Children’s Susceptibility 

Section 6.6 Exposures of Children 

Other Sections of Interest: 

Section 3.8 Biomarkers of Exposure and Effect 

Section 3.11 Methods for Reducing Toxic Effects 

ATSDR Information Center 

Phone: 1-888-42-ATSDR or (404) 498-0110 Fax: (770) 488-4178 

E-mail: atsdric@cdc.gov Internet: http://www.atsdr.cdc.gov 

The following additional material can be ordered through the ATSDR Information Center: 

Case Studies in Environmental Medicine: Taking an Exposure History—The importance of taking an 

exposure history and how to conduct one are described, and an example of a thorough exposure history is 

provided. Other case studies of interest include Reproductive and Developmental Hazards; Skin Lesions 
SYNTHETIC VITREOUS FIBERS viii 

and Environmental Exposures; Cholinesterase-Inhibiting Pesticide Toxicity; and numerous chemicalspecific case studies. 

Managing Hazardous Materials Incidents is a three-volume set of recommendations for on-scene 

(prehospital) and hospital medical management of patients exposed during a hazardous materials incident. 

Volumes I and II are planning guides to assist first responders and hospital emergency department 

personnel in planning for incidents that involve hazardous materials. Volume III—Medical Management 

Guidelines for Acute Chemical Exposures—is a guide for health care professionals treating patients 

exposed to hazardous materials. 

Fact Sheets (ToxFAQs) provide answers to frequently asked questions about toxic substances. 

Other Agencies and Organizations 

The National Center for Environmental Health (NCEH) focuses on preventing or controlling disease, 

injury, and disability related to the interactions between people and their environment outside the 

workplace. Contact: NCEH, Mailstop F-29, 4770 Buford Highway, NE, Atlanta, GA 30341-3724 

• Phone: 770-488-7000 • FAX: 770-488-7015. 

The National Institute for Occupational Safety and Health (NIOSH) conducts research on occupational 

diseases and injuries, responds to requests for assistance by investigating problems of health and safety in 

the workplace, recommends standards to the Occupational Safety and Health Administration (OSHA) and 

the Mine Safety and Health Administration (MSHA), and trains professionals in occupational safety and 

health. Contact: NIOSH, 200 Independence Avenue, SW, Washington, DC 20201 • Phone: 800-356­

4674 or NIOSH Technical Information Branch, Robert A. Taft Laboratory, Mailstop C-19, 4676 

Columbia Parkway, Cincinnati, OH 45226-1998 • Phone: 800-35-NIOSH. 

The National Institute of Environmental Health Sciences (NIEHS) is the principal federal agency for 

biomedical research on the effects of chemical, physical, and biologic environmental agents on human 

health and well-being. Contact: NIEHS, PO Box 12233, 104 T.W. Alexander Drive, Research Triangle 

Park, NC 27709 • Phone: 919-541-3212. 

Referrals 

The Association of Occupational and Environmental Clinics (AOEC) has developed a network of clinics 

in the United States to provide expertise in occupational and environmental issues. Contact: AOEC, 

1010 Vermont Avenue, NW, #513, Washington, DC 20005 • Phone: 202-347-4976 • FAX: 202-347­

4950 • e-mail: AOEC@AOEC.ORG • Web Page: http://www.aoec.org/. 

The American College of Occupational and Environmental Medicine (ACOEM) is an association of 

physicians and other health care providers specializing in the field of occupational and environmental 

medicine. Contact: ACOEM, 55 West Seegers Road, Arlington Heights, IL 60005 • Phone: 847-818­

1800 • FAX: 847-818-9266. 
SYNTHETIC VITREOUS FIBERS ix 

CONTRIBUTORS 

CHEMICAL MANAGER(S)/AUTHOR(S): 

Malcolm Williams, D.V.M., Ph.D. 

ATSDR, Division of Toxicology, Atlanta, GA 

Peter R. McClure, Ph.D., D.A.B.T. 

Andrew McDougal, Ph.D. 

Mario J. Citra, Ph.D. 

Syracuse Research Corporation, North Syracuse, NY 

THE PROFILE HAS UNDERGONE THE FOLLOWING ATSDR INTERNAL REVIEWS: 

1. Health Effects Review. The Health Effects Review Committee examines the health effects 

chapter of each profile for consistency and accuracy in interpreting health effects and classifying 

end points. 

2.	 Minimal Risk Level Review. The Minimal Risk Level Workgroup considers issues relevant to 

substance-specific Minimal Risk Levels (MRLs), reviews the health effects database of each 

profile, and makes recommendations for derivation of MRLs. 

3. Data Needs Review. The Research Implementation Branch reviews data needs sections to assure 

consistency across profiles and adherence to instructions in the Guidance. 

SYNTHETIC VITREOUS FIBERS xi 

PEER REVIEW 

A peer review panel was assembled for synthetic vitreous fibers. The panel consisted of the following 

members: 

1. Jeffrey I. Everitt, D.V.M., Senior Scientist, CIIT Centers for Health Research, Research 

Triangle Park, North Carolina; 

2. Morton Lippmann, Ph.D., Professor of Environmental Medicine, New York University School of 

Medicine, Tuxedo, New York; 

3. John A. Pickrell, Ph.D., D.V.M., Associate Professor of Environmental Toxicology, Kansas State 

University, Diagnostic Medical Pathobiology Department, Manhattan, Kansas; and 

4.	 Ernest McConnell, DVM, MS (path), DABT, DACVP, President, Toxpath Inc., Raleigh, North 

Carolina. 

These experts collectively have knowledge of synthetic vitreous fibers' physical and chemical properties, 

toxicokinetics, key health end points, mechanisms of action, human and animal exposure, and 

quantification of risk to humans. All reviewers were selected in conformity with the conditions for peer 

review specified in Section 104(I)(13) of the Comprehensive Environmental Response, Compensation, 

and Liability Act, as amended. 

Scientists from the Agency for Toxic Substances and Disease Registry (ATSDR) have reviewed the peer 

reviewers' comments and determined which comments will be included in the profile. A listing of the 

peer reviewers' comments not incorporated in the profile, with a brief explanation of the rationale for their 

exclusion, exists as part of the administrative record for this compound. A list of databases reviewed and 

a list of unpublished documents cited are also included in the administrative record. 

The citation of the peer review panel should not be understood to imply its approval of the profile's final 

content. The responsibility for the content of this profile lies with the ATSDR. 

 

SYNTHETIC VITREOUS FIBERS xiii 

CONTENTS 

DISCLAIMER ..............................................................................................................................................ii 

UPDATE STATEMENT .............................................................................................................................iii 

FOREWORD ................................................................................................................................................v 

QUICK REFERENCE FOR HEALTH CARE PROVIDERS....................................................................vii 

CONTRIBUTORS.......................................................................................................................................ix 

PEER REVIEW ...........................................................................................................................................xi 

CONTENTS...............................................................................................................................................xiii 

LIST OF FIGURES ..................................................................................................................................xvii 

LIST OF TABLES.....................................................................................................................................xix 

1. PUBLIC HEALTH STATEMENT..........................................................................................................1 

1.1 WHAT ARE SYNTHETIC VITREOUS FIBERS? ....................................................................1 

1.2 WHAT HAPPENS TO SYNTHETIC VITREOUS FIBERS WHEN THEY ENTER THE 

 ENVIRONMENT? ......................................................................................................................2 

1.3 HOW MIGHT I BE EXPOSED TO SYNTHETIC VITREOUS FIBERS?................................3 

1.4 HOW CAN SYNTHETIC VITREOUS FIBERS ENTER AND LEAVE MY BODY?.............4 

1.5 HOW CAN SYNTHETIC VITREOUS FIBERS AFFECT MY HEALTH?..............................5 

1.6 HOW CAN SYNTHETIC VITREOUS FIBERS AFFECT CHILDREN? .................................8 

1.7 HOW CAN FAMILIES REDUCE THE RISK OF EXPOSURE TO SYNTHETIC 

 VITREOUS FIBERS? .................................................................................................................9 

1.8 IS THERE A MEDICAL TEST TO DETERMINE WHETHER I HAVE BEEN EXPOSED 

TO SYNTHETIC VITREOUS FIBERS?..................................................................................10 

1.9 WHAT RECOMMENDATIONS HAS THE FEDERAL GOVERNMENT MADE TO 

PROTECT HUMAN HEALTH?...............................................................................................10 

1.10 WHERE CAN I GET MORE INFORMATION? .....................................................................11 

2. RELEVANCE TO PUBLIC HEALTH .................................................................................................13 

2.1 BACKGROUND AND ENVIRONMENTAL EXPOSURES TO SYNTHETIC 

 VITREOUS FIBERS IN THE UNITED STATES ...................................................................13 

2.2 SUMMARY OF HEALTH EFFECTS......................................................................................16 

2.3 MINIMAL RISK LEVELS .......................................................................................................22 

3. HEALTH EFFECTS..............................................................................................................................29 

3.1 INTRODUCTION.....................................................................................................................29 

3.2 DISCUSSION OF HEALTH EFFECTS BY ROUTE OF EXPOSURE ..................................29 

3.2.1 Inhalation Exposure ..............................................................................................................31 

3.2.1.1 Death ............................................................................................................................31 

3.2.1.2 Systemic Effects...........................................................................................................31 

3.2.1.3 Immunological and Lymphoreticular Effects...............................................................96 

3.2.1.4 Neurological Effects.....................................................................................................96 

3.2.1.5 Reproductive Effects....................................................................................................96 

3.2.1.6 Developmental Effects .................................................................................................96 

3.2.1.7 Cancer........................................................................................................................... 96 

3.2.2 Oral Exposure......................................................................................................................107 

3.2.2.1 Death ..........................................................................................................................107 

3.2.2.2 Systemic Effects.........................................................................................................107 

3.2.2.3 Immunological and Lymphoreticular Effects.............................................................108 
 

 

 

SYNTHETIC VITREOUS FIBERS xiv 

3.2.2.4 Neurological Effects...................................................................................................108 

3.2.2.5 Reproductive Effects..................................................................................................108 

3.2.2.6 Developmental Effects ...............................................................................................108 

3.2.2.7 Cancer.........................................................................................................................108 

3.2.3 Dermal Exposure.................................................................................................................108 

3.2.3.1 Death ..........................................................................................................................108 

3.2.3.2 Systemic Effects.........................................................................................................108 

3.2.3.3 Immunological and Lymphoreticular Effects.............................................................109 

3.2.3.4 Neurological Effects...................................................................................................109 

3.2.3.5 Reproductive Effects..................................................................................................109 

3.2.3.6 Developmental Effects ...............................................................................................109 

3.2.3.7 Cancer.........................................................................................................................109 

3.2.4 Other Routes of Exposure ...................................................................................................109 

3.3 GENOTOXICITY ...................................................................................................................110 

3.4 TOXICOKINETICS................................................................................................................112 

3.4.1 Absorption...........................................................................................................................112 

3.4.1.1 Inhalation Exposure....................................................................................................112 

3.4.1.2 Oral Exposure.............................................................................................................115 

3.4.1.3 Dermal Exposure ........................................................................................................115 

3.4.2 Distribution .........................................................................................................................115 

3.4.2.1 Inhalation Exposure....................................................................................................115 

3.4.2.2 Oral Exposure.............................................................................................................121 

3.4.2.3 Dermal Exposure ........................................................................................................121 

3.4.2.4 Other Routes of Exposure ..........................................................................................121
 

3.4.3 Metabolism..........................................................................................................................122 

3.4.3.1 Inhalation Exposure....................................................................................................122 

3.4.3.2 Oral Exposure.............................................................................................................123 

3.4.3.3 Dermal Exposure ........................................................................................................123 

3.4.4 Elimination and Excretion...................................................................................................123 

3.4.4.1 Inhalation Exposure....................................................................................................123 

3.4.4.2 Oral Exposure.............................................................................................................124 

3.4.4.3 Dermal Exposure ........................................................................................................124 

3.4.4.4 Other Routes of Exposure ..........................................................................................125
 

3.4.5 Physiologically Based Pharmacokinetic (PBPK)/Pharmacodynamic (PD) Models ...........125 

3.5 MECHANISMS OF ACTION ................................................................................................130 

3.5.1 Pharmacokinetic Mechanisms.............................................................................................130 

3.5.2 Mechanisms of Toxicity......................................................................................................132 

3.5.3 Animal-to-Human Extrapolations.......................................................................................134 

3.6 TOXICITIES MEDIATED THROUGH THE NEUROENDOCRINE AXIS ........................136 

3.7 CHILDREN’S SUSCEPTIBILITY.........................................................................................137 

3.8 BIOMARKERS OF EXPOSURE AND EFFECT ..................................................................139 

3.8.1 Biomarkers Used to Identify or Quantify Exposure to Synthetic Vitreous Fibers..............140 

3.8.2 Biomarkers Used to Characterize Effects Caused by Synthetic Vitreous Fibers................141 

3.9 INTERACTIONS WITH OTHER CHEMICALS ..................................................................142 

3.10 POPULATIONS THAT ARE UNUSUALLY SUSCEPTIBLE.............................................143 

3.11 METHODS FOR REDUCING TOXIC EFFECTS.................................................................144 

3.11.1 Reducing Peak Absorption Following Exposure ............................................................145 

3.11.2 Reducing Body Burden...................................................................................................145 

3.11.3 Interfering with the Mechanism of Action for Toxic Effects .........................................145 

3.12 ADEQUACY OF THE DATABASE......................................................................................146 
SYNTHETIC VITREOUS FIBERS xv 

3.12.1 Existing Information on Health Effects of Synthetic Vitreous Fibers............................146 

3.12.2 Identification of Data Needs ...........................................................................................146 

3.12.3 Ongoing Studies..............................................................................................................161 

4. CHEMICAL AND PHYSICAL INFORMATION..............................................................................163 

4.1 CHEMICAL IDENTITY.........................................................................................................163 

4.2 PHYSICAL AND CHEMICAL PROPERTIES......................................................................165 

5. PRODUCTION, IMPORT/EXPORT, USE, AND DISPOSAL..........................................................171 

5.1 PRODUCTION .......................................................................................................................171 

5.2 IMPORT/EXPORT .................................................................................................................175 

5.3 USE..........................................................................................................................................175 

5.4 DISPOSAL..............................................................................................................................177 

6. POTENTIAL FOR HUMAN EXPOSURE .........................................................................................179 

6.1 OVERVIEW............................................................................................................................179 

6.2 RELEASES TO THE ENVIRONMENT................................................................................182 

6.2.1 Air .......................................................................................................................................182 

6.2.2 Water...................................................................................................................................183 

6.2.3 Soil ......................................................................................................................................183 

6.3 ENVIRONMENTAL FATE....................................................................................................183
 

6.3.1 Transport and Partitioning...................................................................................................183 

6.3.2 Transformation and Degradation ........................................................................................184 

6.3.2.1 Air...............................................................................................................................184 

6.3.2.2 Water ..........................................................................................................................184 

6.3.2.3 Sediment and Soil.......................................................................................................184 

6.4 LEVELS MONITORED OR ESTIMATED IN THE ENVIRONMENT...............................184 

6.4.1 Air .......................................................................................................................................184 

6.4.2 Water...................................................................................................................................188 

6.4.3 Sediment and Soil ...............................................................................................................188 

6.4.4 Other Environmental Media................................................................................................188 

6.5 GENERAL POPULATION AND OCCUPATIONAL EXPOSURE .....................................188 

6.6 EXPOSURES OF CHILDREN...............................................................................................200 

6.7 POPULATIONS WITH POTENTIALLY HIGH EXPOSURES ...........................................201 

6.8 ADEQUACY OF THE DATABASE......................................................................................202 

6.8.1 Identification of Data Needs ...............................................................................................203 

6.8.2 Ongoing Studies ..................................................................................................................205 

7. ANALYTICAL METHODS ...............................................................................................................207 

7.1 BIOLOGICAL MATERIALS.................................................................................................209 

7.2 ENVIRONMENTAL SAMPLES............................................................................................210 

7.3 ADEQUACY OF THE DATABASE......................................................................................212 

7.3.1 Identification of Data Needs ...............................................................................................212 

7.3.2 Ongoing Studies ..................................................................................................................215 

8. REGULATIONS AND ADVISORIES ...............................................................................................217 

9. REFERENCES .................................................................................................................................... 221 

10. GLOSSARY ...................................................................................................................................... 269 
SYNTHETIC VITREOUS FIBERS xvi 

APPENDICES 

A. ATSDR MINIMAL RISK LEVELS AND WORKSHEETS .............................................................A-1 

B. USER’S GUIDE.................................................................................................................................. B-1 

C. ACRONYMS, ABBREVIATIONS, AND SYMBOLS...................................................................... C-1 

D. INDEX ................................................................................................................................................D-1 
SYNTHETIC VITREOUS FIBERS xvii 

LIST OF FIGURES 

2-1. IARC (2002) Categories of Synthetic Vitreous Fibers....................................................................... 14 

3-1. Levels of Significant Exposure to Synthetic Vitreous Fibers—Inhalation......................................... 67 

3-2. Existing Information on Health Effects of Synthetic Vitreous Fibers.............................................. 147 

6-1. Frequency of NPL Sites with Synthetic Vitreous Fiber Contamination........................................... 180 

SYNTHETIC VITREOUS FIBERS xix 

LIST OF TABLES 

2-1. BMCs and BMCLs for 10% Lung Weight Increase and Pulmonary Lesion Scores of 1 in Rats 

Exposed to RCF1 for 24 Months ........................................................................................................ 24 

2-2. Non-neoplastic Lung Responses in F344 Rats Exposed for 24 Months to RCF1 .............................. 26 

3-1. Levels of Significant Exposure to Synthetic Vitreous Fibers............................................................. 32 

3-2. Lung Clearance of Fibers with Lengths >20 μm in F344 Male Rats Following Nose-only Inhalation 

Exposure (6 hours/day for 5 days) to 19 Different Synthetic Vitreous Fibers or Two Types of 

Asbestos............................................................................................................................................ 120 

3-3. Comparative Human and Rat Anatomical and Physiological Parameters Relevant to Alveolar 

Retention of Refractory Ceramic Fibers ........................................................................................... 129 

4-1. Chemical Identity of Some Types of Synthetic Vitreous Fibers ...................................................... 164 

4-2. Physical Properties of Some Types of Synthetic Vitreous Fibers .................................................... 167 

4-3. Measured Nominal Diameters of Glass Wool, Rock Wool, Slag Wool, Refractory Ceramic Fibers, 

and a Special Purpose Glass Fiber.................................................................................................... 169 

4-4. Statistical Analysis of Airborne Fibers Under Different Occupational Settings .............................. 170 

5-1. Production Volumes of Glass Wool, Rock Wool, and Slag Wool Products in the United States .... 172 

5-2. Continuous Filament Glass Fiber Production in the United States .................................................. 173 

5-3. U.S. Import/Export Volume of Glass Fibers (Including Glass Wool), Mineral Wool and Refractory
 

Ceramic Goods ................................................................................................................................. 176 

6-1. Airborne Concentrations of Synthetic Vitreous Fibers in Buildings in Denmark ............................ 187 

6-2. Concentrations (mg/m3

) of Total Suspended Airborne Particulate Matter in 16 Facilities in the 

United States..................................................................................................................................... 191 

6-3. Concentrations (fiber(s)/cc) of Total Airborne Fibers in 16 Facilities in the United States............. 192 

6-4. Exposures to Synthetic Vitreous Fibers Categorized by Industrial Sector ....................................... 194 

6-5. Exposures to Synthetic Vitreous Fibers Categorized by Product Type............................................ 195 

6-6. Exposures to Synthetic Vitreous Fibers Categorized by Job Type................................................... 197 

6-7. Typical Exposures in the Manufacture and Use of Refractory Ceramic Fibers ............................... 199 

7-1. Analytical Methods for Determining Synthetic Vitreous Fibers in Biological Samples.................. 211 
SYNTHETIC VITREOUS FIBERS xx 

7-2. Analytical Methods for Determining Synthetic Vitreous Fibers in Environmental Samples........... 213 

8-1. Regulations and Guidelines Applicable to Synthetic Vitreous Fibers.............................................. 218 
SYNTHETIC VITREOUS FIBERS 1 

1. PUBLIC HEALTH STATEMENT 

This public health statement tells you about synthetic vitreous fibers (SVFs) and the effects of 

exposure to them. 

The Environmental Protection Agency (EPA) identifies the most serious hazardous waste sites in 

the nation. These sites are then placed on the National Priorities List (NPL) and are targeted for 

long-term federal clean-up activities. Synthetic vitreous fibers have not been detected in the 

1,647 current or former NPL sites. Although the total number of NPL sites evaluated for these 

substances is not known, the possibility exists that synthetic vitreous fibers may be found in the 

future as more sites are evaluated. This information is important because these sites may be 

sources of exposure and exposure to these substances may harm you. 

When a substance is released from a large area, such as an industrial plant, or from a container, 

such as a drum or bottle, it enters the environment. This release does not always lead to 

exposure. You are exposed to a substance only when you come in contact with it. You may be 

exposed by breathing, eating, or drinking the substance, or by skin contact. 

If you are exposed to synthetic vitreous fibers, many factors determine whether you'll be harmed. 

These factors include the dose (how much), the duration (how long), and how you come in 

contact with them. You must also consider the other chemicals you're exposed to and your age, 

sex, diet, family traits, lifestyle, and state of health. 

1.1 WHAT ARE SYNTHETIC VITREOUS FIBERS? 

Synthetic vitreous fibers are a group of fibrous inorganic materials that contain aluminum or 

calcium silicates and other trace oxides and metals, and are made from rock, slag, clay, or glass. 

These fibers differ from natural mineral fibers such as asbestos because they do not have a 

crystalline molecular structure. The randomly oriented molecular structure of synthetic vitreous 

fibers is called an amorphous structure. There are two broad categories of synthetic vitreous 
SYNTHETIC VITREOUS FIBERS 2 

1. PUBLIC HEALTH STATEMENT 

fibers: filaments and wools. The filaments consist of continuous glass filaments, while the wools 

are subdivided into glass wool, rock wool, slag wool, refractory ceramic fibers, and other types 

of newer fibers. The primary uses of synthetic vitreous fibers are for heat and sound insulating 

purposes, to reinforce other materials, and as filtration materials. Glass wools are some of the 

most widely used insulating materials in homes and buildings. The production and use of 

synthetic vitreous fibers has increased in recent years because these products are often used as a 

replacement for asbestos. 

A fiber is simply a long, slender particle. Technically, to be counted as a fiber, the particle must 

be at least 5 micrometers long (1 micrometer equals 1/1,000,000 of a meter and has the symbol 

μm), and have an aspect ratio of at least 3 to 1 or sometimes 5 to 1 (the aspect ratio is the ratio of 

a fiber’s length to its diameter). The diameter of a fiber is an important property because very 

thin fibers are more easily suspended in air than thick fibers, and they can be breathed in and 

deposited deep in the lungs. Only very thin fibers with diameters less than 3 μm are able to be 

breathed into the lower respiratory tract of humans. Thicker fibers are deposited on the mucouslined surface of the upper respiratory tract, which includes the nose and mouth. The World 

Health Organization (WHO) counts respirable fibers as particles with lengths greater than 5 μm, 

diameters less than 3 μm, and aspect ratios ≥3:1. Depending upon the way that they are 

produced, fibers can have relatively large or small diameters. Generally speaking, glass wool, 

rock wool, slag wool, and refractory ceramic fibers have the smallest diameters, while 

continuous filament glass fibers have the largest diameters. 

See Chapters 4 and 5 for more information on the properties and uses of synthetic vitreous fibers. 

1.2 WHAT HAPPENS TO SYNTHETIC VITREOUS FIBERS WHEN THEY ENTER 

THE ENVIRONMENT? 

Synthetic vitreous fibers do not evaporate into air or dissolve in water. They are generally not 

broken down to other compounds in the environment and will remain virtually unchanged over 

long periods. Eventually, synthetic vitreous fibers will be broken down if the water or soil is 

very acidic or very alkaline. Fibers can enter the air, water, and soil from the manufacture, use, 
SYNTHETIC VITREOUS FIBERS 3 

1. PUBLIC HEALTH STATEMENT 

and disposal of synthetic vitreous fiber-containing materials. Fibers with small diameters 

become airborne more easily than thick fibers, and can be transported by wind for longer 

distances. Synthetic vitreous fibers are not likely to move through soil. 

See Chapter 6 for more information on the behavior of synthetic vitreous fibers in the 

environment. 

1.3 HOW MIGHT I BE EXPOSED TO SYNTHETIC VITREOUS FIBERS? 

If materials containing synthetic vitreous fibers, such as insulation or ceiling boards in your 

home or where you work, are disturbed, synthetic vitreous fibers can become airborne. When 

these fibers become airborne, you can be exposed to low levels of synthetic vitreous fibers 

primarily by breathing air. Your skin and eyes can also be exposed to synthetic vitreous fibers if 

you install your own home insulation or come into contact with insulation in your home without 

using protective equipment such as gloves, protective glasses, or masks. 

The vast majority of exposure to synthetic vitreous fibers occurs to workers who produce or use 

synthetic vitreous fiber-containing products. Employees at manufacturing facilities where 

synthetic vitreous fibers products are produced, as well as workers who regularly install or come 

into contact with insulating material, are most frequently exposed to synthetic vitreous fibers. 

Workers involved in demolition work, as well as in building maintenance and repair, are 

potentially exposed to higher levels of synthetic vitreous fibers once these materials are 

disturbed. 

See Chapters 3 and 6 for more information on how you could be exposed to synthetic vitreous 

fibers. 
SYNTHETIC VITREOUS FIBERS 4 

1. PUBLIC HEALTH STATEMENT 

1.4 HOW CAN SYNTHETIC VITREOUS FIBERS ENTER AND LEAVE MY BODY? 

If you breathe synthetic vitreous fibers, some will be deposited in the nasal and oral passages, 

and on the surfaces that line your lungs. Most fibers deposited in the nasal and upper lung 

airways are removed by being carried away in a layer of mucous to the throat, where they are 

swallowed into the stomach. This usually takes place within a few hours. Fibers deposited in 

the deepest parts of the lungs where gas exchange occurs are removed more slowly by special 

cells called macrophages. Macrophages can engulf the fibers and move them to the mucous 

layer and the larynx where they can be swallowed. Swallowed fibers and macrophages are 

excreted in the feces within a few days. 

Synthetic vitreous fibers deposited in the gas exchange area of the lungs also slowly dissolve in 

lung fluid. Fibers that are partially dissolved in lung fluid are more easily broken into shorter 

fibers. Shorter fibers are more easily engulfed by macrophages and removed from the lung than 

long fibers. Synthetic vitreous fibers dissolve more readily in the lung than asbestos fibers. 

Refractory ceramic fibers dissolve more slowly than most types of insulation (e.g., glass wools, 

stone wools, and slag wools). 

If you swallow synthetic vitreous fibers (by eating, drinking, or by swallowing fibers that have 

moved from nasal or lung airways to your larynx), nearly all of the fibers pass through your 

intestines within a few days and are excreted in the feces. 

If you get synthetic vitreous fibers on your skin or in your eyes, very few of these fibers, if any, 

pass through into your body. 

See Chapter 3 for more information on how synthetic vitreous fibers enter and leaves the body. 
SYNTHETIC VITREOUS FIBERS 5 

1. PUBLIC HEALTH STATEMENT 

1.5 HOW CAN SYNTHETIC VITREOUS FIBERS AFFECT MY HEALTH? 

To protect the public from the harmful effects of toxic chemicals and to find ways to treat people 

who have been harmed, scientists use many tests. 

One way to see if a chemical will hurt people is to learn how the chemical is absorbed, used, and 

released by the body; for some chemicals, animal testing may be necessary. Animal testing may 

also be used to identify health effects such as cancer or birth defects. Without laboratory 

animals, scientists would lose a basic method to get information needed to make informed 

decisions to protect public health. Scientists have the responsibility to treat research animals 

with care and compassion. Laws today protect the welfare of research animals, and scientists 

must comply with strict animal care guidelines. 

Synthetic vitreous fibers can cause irritation of the eyes and skin known as “fiberglass itch.” 

They can also irritate the upper respiratory tract (the nose, throat) and parts of the lung, causing 

sore throat, nasal congestion, and cough. These effects usually go away with time. Because 

most people are not exposed to high levels of synthetic vitreous fibers, serious health effects are 

not expected to happen in most people. 

Most of the information regarding the possible effects of repeated exposure to synthetic vitreous 

fibers in people comes from large studies of workers who make synthetic vitreous fibers. Very 

few effects were detected. A few workers who made refractory ceramic fibers had pleural 

plaques on the lining of their chests. These plaques did not seem to harm the workers. Other 

workers who smoked could not breathe quite as well as smokers who did not work with 

refractory ceramic fibers. Nonsmoking refractory ceramic fiber workers could breathe as well as 

other nonsmokers. This suggests that repeatedly breathing in refractory ceramic fibers from 

workplace air worsens the effects of smoking. Pleural plaques and decreased breathing ability 

have not been found in workers who made glass wool and stone wool. Other studies have found 

that the numbers of deaths from lung diseases, including lung cancer or mesothelioma, in groups 

of workers involved in the manufacture of glass wool, stone wool, or refractory ceramic fibers 

are not consistently different from what is found in the general U.S. population. Mesothelioma is 
 

SYNTHETIC VITREOUS FIBERS 6 

1. PUBLIC HEALTH STATEMENT 

a cancer of the membrane lining the lung. Increased risk for mesothelioma has been found in 

asbestos workers, but increased risks for this cancer have not been found in workers involved in 

the manufacture of synthetic vitreous fibers. 

Results from animal experiments show that when synthetic vitreous fibers or other inhaled dust 

particles are deposited in the deepest part of the lung in high numbers, the lung responds with a 

process called pulmonary inflammation. In this process, macrophage numbers in the lung 

increase so that they can engulf and move the fibers out of the lung. When high numbers of 

fibers are deposited, the macrophages can become clumped together. If pulmonary inflammation 

continues, the cells lining the lung may thicken from a process called bronchiolization. 

Bronchiolization may reduce the amount of oxygen that the body gets from the air during 

breathing. If exposure stops, deposited synthetic vitreous fibers slowly dissolve in the lung fluid 

or are moved out of the lung by the macrophages, and pulmonary inflammation disappears with 

time. 

Results from animal studies also show that repeatedly breathing high levels of some types of 

synthetic vitreous fibers may cause a slow buildup of scar-like tissue in the lungs and in the 

membrane surrounding the lungs. This scar-like tissue does not expand and contract like normal 

lung tissue, and breathing can become difficult. This condition is called pulmonary fibrosis. The 

types of synthetic vitreous fibers that cause this condition in animals stay in the lung for longer 

periods of time than the types that do not. They are called durable or biopersistent synthetic 

vitreous fibers. Results from animal studies also show that repeatedly breathing high levels of 

durable synthetic vitreous fibers may also cause cancer of the lung and mesothelioma. The most 

common types of glass wools, stone wools, or slag wools used for insulation are less durable 

than refractory ceramic fibers. In rat studies, they did not cause the severe lung effects caused by 

the more durable refractory ceramic fibers. 

Scientists studying pulmonary fibrosis, lung cancer, and mesothelioma in animals from durable 

synthetic vitreous fibers have shown that the development of these conditions depends on four 

factors: dose, duration, dimension, and durability. Dose is the amount of fibers deposited in the 

lung, and duration is the time period when exposure occurs. High doses and long durations of 
 

SYNTHETIC VITREOUS FIBERS 7 

1. PUBLIC HEALTH STATEMENT 

exposure are required for these conditions to develop. Dimension refers to the length and 

diameter of the fibers. Fibers with diameters greater than about 3 μm are not inhaled into the 

deepest regions of the lungs. Fibers with lengths greater than about 15–20 μm are not engulfed 

by macrophages, and are more likely to lead to lung injury than shorter fibers that are more 

readily removed by macrophages. Durability refers to how readily a fiber dissolves in lung fluid. 

Different types of synthetic vitreous fibers have different durabilities due to differences in 

chemical makeup. Most synthetic vitreous fibers used as insulation in homes and buildings, such 

as fiberglass wools and stone wools, are more readily dissolved in lung fluid than are refractory 

ceramic fibers, which are used in insulation materials for furnaces. Long, durable fibers 

deposited in the gas-exchange region of the lung can lead to long-term inflammation, pulmonary 

fibrosis, lung cancer, or mesothelioma. 

Levels of synthetic vitreous fibers in outdoor air, indoor air, and in most workplaces are usually 

well below levels that caused reversible pulmonary inflammation in animals or levels of durable 

synthetic vitreous fibers that caused pulmonary fibrosis, lung cancer, or mesothelioma in 

animals. For example, levels of a refractory ceramic fiber that caused pulmonary fibrosis, lung 

cancer, and mesothelioma in rats are about one million times higher than levels of synthetic 

vitreous fibers detected in outdoor air close to synthetic vitreous fiber manufacturing factories, or 

indoor air from buildings with fiberglass or stone wool insulation. The levels experienced by the 

diseased rats are about 50 times higher than levels of synthetic vitreous fibers in the most dusty 

workplaces where insulation containing synthetic vitreous fibers was removed or installed. 

In 2002, the International Agency for Research on Cancer (IARC) considered all of the evidence 

regarding the possible carcinogenicity of synthetic vitreous fibers. Much of the evidence was 

collected in the 1990s and was not available for earlier assessments made by the U.S. 

Department of Health and Human Services (DHHS). IARC determined that refractory ceramic 

fibers are possibly carcinogenic to humans because of their high biopersistence. IARC also 

determined that insulation glass wool, stone wool, and slag wool, and continuous filament glass 

were not classifiable as to carcinogenicity to humans because of inadequate evidence of 

carcinogenicity in humans and the relatively low biopersistence of these materials. EPA has not 
SYNTHETIC VITREOUS FIBERS 8 

1. PUBLIC HEALTH STATEMENT 

assessed the potential carcinogenicity of glass wool, stone wool, slag wool, or continuous 

filament glass, but has classified refractory ceramic fibers as a probable human carcinogen. 

See Chapters 2 and 3 for more information on how synthetic vitreous fibers may affect your 

health. 

1.6 HOW CAN SYNTHETIC VITREOUS FIBERS AFFECT CHILDREN? 

This section discusses potential health effects from exposures during the period from conception 

to maturity at 18 years of age in humans. 

Because synthetic vitreous fibers are not absorbed into the body (when inhaled or ingested), it is 

unlikely that they would cause birth defects or be transferred in breast milk to nursing infants. 

Like adults, children who are exposed to synthetic vitreous fibers may experience irritation of the 

eyes, skin, and upper respiratory tract. Children breathe differently and have different lung 

structures than do adults. It is not likely that these differences will cause a greater amount of 

synthetic vitreous fibers to stay in the lungs of children than in the lungs of adults. 

It is possible that exposure of young children to highly durable fibers could lead to pulmonary 

effects after very long latency periods. However, there is no evidence to support this possibility, 

and the durability of many types of synthetic vitreous fibers in the lung is low. This concern also 

has been raised for children exposed to asbestos fibers, which are more durable than synthetic 

vitreous fibers, but, as with synthetic vitreous fibers, there is inadequate evidence to support the 

idea that exposed young children may be at greater risk to develop pulmonary effects from 

durable fibers than are adults. 
SYNTHETIC VITREOUS FIBERS 9 

1. PUBLIC HEALTH STATEMENT 

1.7 HOW CAN FAMILIES REDUCE THE RISK OF EXPOSURE TO SYNTHETIC 

VITREOUS FIBERS? 

If your doctor finds that you have been exposed to significant amounts of synthetic vitreous 

fibers, ask whether your children might also be exposed. Your doctor might need to ask your 

state health department to investigate. 

Very low levels of synthetic vitreous fibers can be found in virtually all homes, buildings, and 

outside air, but there is little concern regarding these low levels. The most important way that 

families can lower their exposures to synthetic vitreous fibers is to be aware of the sources of 

synthetic vitreous fibers in their homes and avoid exposure to these sources. The most common 

source of synthetic vitreous fibers in a home is from insulating material that may be in your attic 

or walls. Damaged or deteriorating ceiling boards are another potential source. As long as the 

materials are not physically disturbed or breaking down, the levels of synthetic vitreous fibers in 

the air should be very low. Relatively high levels of airborne synthetic vitreous fibers have been 

detected during the installation of insulating materials in attics, but these levels decline rapidly in 

1 or 2 days as airborne dust settles. If you are installing your own insulation, wear protective 

clothing and masks, and follow the recommendations provided by the manufacturer for installing 

this material. 

You can bring synthetic vitreous fibers home in the dust on your hands or clothes if you work in 

facilities that produce or use synthetic vitreous fibers, or install or remove materials with 

synthetic vitreous fibers. Your occupational health and safety (OHS) officer can and should tell 

you whether chemicals you work with are dangerous and likely to be carried home on your 

clothes, body, or tools. Your OHS officer can also tell you whether you should be showering 

and changing clothes before you leave work, storing your street clothes in a separate area of the 

workplace, or laundering your work clothes at home separately from other clothes. Your 

employer should have Material Safety Data Sheets (MSDSs) for many of the chemicals used at 

your place of work, as required by the Occupational Safety and Health Administration (OSHA). 

Information on these sheets should include chemical names and hazardous ingredients, important 

properties (such as fire and explosion data), potential health effects, how you get the chemical(s) 
SYNTHETIC VITREOUS FIBERS 10 

1. PUBLIC HEALTH STATEMENT 

in your body, how to handle the materials properly, and what to do in an emergency. Your 

employer is legally responsible for providing a safe workplace and should freely answer your 

questions about hazardous chemicals. Either OSHA or your OSHA-approved state occupational 

safety and health program can answer any further questions and help your employer identify and 

correct problems with hazardous substances. OSHA or your OSHA-approved state occupational 

safety and health program will listen to your formal complaints about workplace health hazards 

and inspect your workplace when necessary. Employees have a right to safety and health on the 

job without fear of punishment. 

1.8 IS THERE A MEDICAL TEST TO DETERMINE WHETHER I HAVE BEEN 

EXPOSED TO SYNTHETIC VITREOUS FIBERS? 

No tests are specific for determining whether or not you have been exposed to synthetic vitreous 

fibers. Because synthetic vitreous fibers leave the body quickly, most nonspecific tests would 

not be very useful. A chest x-ray is a common method to determine if you have certain 

conditions, such as pleural plaques, lung or pleural fibrosis, lung tumors, or mesotheliomas, but 

x-rays cannot show the presence of fibers in the lung. 

1.9 WHAT RECOMMENDATIONS HAS THE FEDERAL GOVERNMENT MADE TO 

PROTECT HUMAN HEALTH? 

The federal government develops regulations and recommendations to protect public health. 

Regulations can be enforced by law. Federal agencies that develop regulations for toxic 

substances include the Environmental Protection Agency (EPA), the Occupational Safety and 

Health Administration (OSHA), and the Food and Drug Administration (FDA). 

Recommendations provide valuable guidelines to protect public health but cannot be enforced by 

law. Federal organizations that develop recommendations for toxic substances include the 

Agency for Toxic Substances and Disease Registry (ATSDR) and the National Institute for 

Occupational Safety and Health (NIOSH). 
SYNTHETIC VITREOUS FIBERS 11 

1. PUBLIC HEALTH STATEMENT 

Regulations and recommendations can be expressed in not-to-exceed levels in air, water, soil, or 

food that are usually based on levels that affect animals; they are then adjusted to help protect 

people. Sometimes these not-to-exceed levels differ among federal organizations because of 

different exposure times (an 8-hour workday or a 24-hour day), the use of different animal 

studies, or other factors. 

Recommendations and regulations are also periodically updated as more information becomes 

available. For the most current information, check with the federal agency or organization that 

provides it. Some regulations and recommendations for synthetic vitreous fibers include the 

following: 

In 1999, a Health and Safety Partnership Program was established as a voluntary workplace 

safety program for workers involved in the manufacture, fabrication, installation, and removal of 

glass wool, rock wool, and slag wool products. The program was established as a result of 

negotiations between the OSHA, the North American Insulation Manufacturers Association, the 

National Insulation Association, and the Insulation Contractors Association of America. The 

program established a voluntary 8-hour time-weighted average (TWA) permissible exposure 

limit (PEL) of 1 respirable fiber per cc of air. Under this agreement, respirable fibers are 

counted as particles with length greater than 5 μm, diameter less than 3 μm, and aspect ratio 

greater than or equal to 3:1. The agreement specifies that when the PEL is exceeded in a 

workplace (such as when insulation is blown into attics or removed), workers will wear NIOSH 

certified dust respirators. 

1.10 WHERE CAN I GET MORE INFORMATION? 

If you have any more questions or concerns, please contact your community or state health or 

environmental quality department, or contact ATSDR at the address and phone number below. 
 

 

 

 

SYNTHETIC VITREOUS FIBERS 12 

1. PUBLIC HEALTH STATEMENT 

ATSDR can also tell you the location of occupational and environmental health clinics. These 

clinics specialize in recognizing, evaluating, and treating illnesses resulting from exposure to 

hazardous substances. 

Toxicological profiles are also available on-line at www.atsdr.cdc.gov and on CD-ROM. You 

may request a copy of the ATSDR ToxProfilesTM CD-ROM by calling the information and 

technical assistance toll-free number at 1-888-42ATSDR (1-888-422-8737), by email at 

atsdric@cdc.gov, or by writing to: 

Agency for Toxic Substances and Disease Registry 

 Division of Toxicology 

1600 Clifton Road NE 

 Mailstop F-32 

 Atlanta, GA 30333 

 Fax: 1-770-488-4178 

For-profit organizations may request a copy of final profiles from the following: 

National Technical Information Service (NTIS) 

5285 Port Royal Road 

 Springfield, VA 22161 

 Phone: 1-800-553-6847 or 1-703-605-6000 

 Web site: http://www.ntis.gov/ 
SYNTHETIC VITREOUS FIBERS 13 

2. RELEVANCE TO PUBLIC HEALTH 

2.1 BACKGROUND AND ENVIRONMENTAL EXPOSURES TO SYNTHETIC VITREOUS 

FIBERS IN THE UNITED STATES 

Synthetic vitreous fibers are inorganic fibrous materials, manufactured principally from glass, rock, 

minerals, slag, and processed inorganic oxides. Synthetic vitreous fibers are manufactured by several 

processes, all of which involve cooling of a stream of high-temperature, molten inorganic oxides. 

Commercially important synthetic vitreous fibers are primarily silica-based, but contain various amounts 

of other oxides (e.g., aluminum, boron, calcium, or iron oxides). Synthetic vitreous fibers have 

amorphous molecular structures, while naturally occurring mineral fibers, such as asbestos, possess 

crystal structures. In the past, synthetic vitreous fibers were classified into three categories: fibrous glass; 

rock wool and slag wool (sometimes collectively referred to as mineral wool); and refractory ceramic 

fibers. The fibrous glass category included continuous filament glass fibers (sometimes called textile 

fibers) and glass wools. Recently, the World Health Organization (WHO) IARC classified synthetic 

vitreous fibers into two broad categories: filaments and wools. A schematic of this classification scheme 

is shown in Figure 2-1. The filaments category refers to glass fibers that are produced by extrusion 

(continuous glass filaments). IARC noted that more than 98% of currently produced continuous glass 

filaments are for electrical applications. The wools category includes five subgroups: glass wool, rock 

wool, slag wool, refractory ceramic fibers, and other fibers. Included in the glass wool category are the 

subgroups, insulation wools and special purpose fibers. The special purpose fiber group includes glass 

fibers produced by flame attenuation for special applications such as high-efficiency air filtration and 

include special fine-diameter glass fibers. The other fibers group includes fibers such as alkaline earth 

silicate wools and high-alumina, low-silica wools that have been recently developed to be more 

biosoluble than older high-temperature synthetic vitreous fibers such as refractory ceramic fibers or rock 

wools. 

The production and use of synthetic vitreous fibers can cause their release to the environment. Glass 

wool, rock wool, and slag wool are primarily used in insulating materials for homes, buildings, and 

appliances. Continuous filament fibers have been used to reinforce plastics, cement, papers, and roofing 

materials or woven into industrial fabrics, and currently are used mostly for electrical purposes. 

Refractory ceramic fibers are primarily used in insulating materials that require very high temperature 
SYNTHETIC VITREOUS FIBERS 14 

2. RELEVANCE TO PUBLIC HEALTH 

Figure 2-1. IARC (2002) Categories of Synthetic Vitreous Fibers 

Synthe tic Vitreous 

Fibe rs 

Filaments 

Continuous 

glass filaments 

Wools 

Glass wool Rock wool Slag wool Refractory 

ceramic fibers Other fibers 

Insulation wool Special 

purpose fibers 
 

SYNTHETIC VITREOUS FIBERS 15 

2. RELEVANCE TO PUBLIC HEALTH 

resistance (e.g., furnace insulation). Approximately 80% of the synthetic vitreous fibers produced and 

used in the United States are glass wool, rock wool, and slag wool. Refractory ceramic fibers only 

account for about 2% of the total amount of synthetic vitreous fibers produced. 

Synthetic vitreous fibers are persistent in the environment because they are not removed by mechanisms 

that usually degrade organic compounds (e.g., biodegradation, photolysis). Small diameter synthetic 

vitreous fibers with large surface areas can undergo dissolution in aqueous solutions, particularly at very 

high or very low pH levels, but this is more important in biological systems than in the environment (see 

Section 3.4 for more details regarding dissolution in physiologic fluids). The transport and partitioning of 

synthetic vitreous fibers in the environment are largely governed by their size. Large fibers are removed 

from air and water by gravitational settling at a rate primarily dependent on their diameter, but small 

diameter fibers may remain suspended for longer periods of time before settling down to the ground. 

Inhalation exposure to airborne synthetic vitreous fibers is of public health concern because, like other 

particulate matter, fibers that get suspended in air can be inhaled and deposited in the lung. 

Measurements to determine the concentration of synthetic vitreous fibers in air samples are usually 

reported as the number of fiber(s) per cubic centimeter of air (fiber/cc). Different studies have used 

different rules for counting fibers in air samples, but in general, a fiber is a particle that has a length 

≥5 μm and a length:diameter ratio (aspect ratio) of ≥3:1 or ≥5:1. The WHO counts fibers as particles with 

lengths >5 μm, widths <3 μm, and aspect ratios ≥3:1. The National Institute for Occupational Safety and 

Health (NIOSH) counts fibers as particles with lengths >5 μm and aspect ratios ≥3:1. The levels of 

synthetic vitreous fibers in air are measured by phase contrast microscopy (PCM), transmission electron 

microscopy (TEM), or scanning electron microscopy (SEM) (see Chapter 7 for more details). A human 

respirable fiber (a fiber that can be inhaled and reach the lower air-exchange portion of the respiratory 

tract) is usually defined as a fiber having a diameter <3 μm. 

When materials containing synthetic vitreous fibers are physically disturbed, fibers can become 

suspended in indoor or outdoor air. In general, fibers with small diameters are more easily suspended and 

remain suspended in air longer than larger-diameter fibers. Among synthetic vitreous fiber types, 

continuous filament glass fibers usually have the largest average diameters, while refractory ceramic 

fibers, glass wool, rock wool, and slag wool generally have smaller average diameters (see Chapter 4 for 

more details). Levels of synthetic vitreous fibers detected in outdoor or indoor air samples are very low, 

usually on the order of about ≤0.0001 NIOSH fiber/cc. In workplaces that manufacture synthetic vitreous 
SYNTHETIC VITREOUS FIBERS 16 

2. RELEVANCE TO PUBLIC HEALTH 

fibers, reported air concentrations have mostly been reported to be <0.1–1 NIOSH fiber/cc. Higher levels 

have been observed during the installation of insulation in a home or building (respirable airborne levels 

>1 fiber/cc have been observed); however, these levels quickly fall back to preinstallation levels within 

1 or 2 days. The geometric mean concentration of respirable synthetic vitreous fibers ranged from 0.01 to 

3.51 fibers/cc at five construction sites where either refractory ceramic fibers, rock wool, or glass wool 

insulating materials were being installed or removed. The greatest levels were observed during the 

removal of refractory ceramic fiber insulating material from the inside walls of industrial furnaces, and 

the lowest levels were observed during the installation of fiberglass panels around ventilation ducts at an 

industrial construction site. 

2.2 SUMMARY OF HEALTH EFFECTS 

Reversible acute irritations of the skin, eyes, and upper respiratory tract are well-known health hazards 

associated with direct dermal and inhalation exposure to refractory ceramic fibers, fibrous glass, rock 

wool, or slag wool in construction and manufacturing workplaces. Wearing protective clothing and 

respiratory equipment has been recommended to prevent these health hazards (and possible chronic health 

hazards) when time-weighted average (TWA) airborne concentrations of fibers exceed recommended 

occupational exposure limits of 1 NIOSH fiber (length >5 μm; aspect ratio ≥3:1)/cc for continuous 

filament glass fibers, glass wool, rock wool, slag wool, and special purpose glass fibers or 0.2 NIOSH 

fibers/cc for refractory ceramic fibers. 

Although several respiratory health effects have been associated with occupational exposure to asbestos 

(pulmonary or pleural fibrosis [i.e., tissue scarring], lung cancer, and pleural or peritoneal mesothelioma), 

none of these diseases has been associated with occupational exposure during the manufacture of 

synthetic vitreous fibers. Results from animal studies indicate that high-level inhalation exposure to any 

synthetic vitreous fiber may cause reversible pulmonary inflammation, but only the most biopersistent of 

synthetic vitreous fibers have been demonstrated to produce irreversible pleural or pulmonary fibrosis, 

lung cancer, or mesothelioma. Health effects at other target organs are not expected from exposure to 

airborne synthetic vitreous fibers. 

Mechanistic and pharmacokinetic studies with asbestos and synthetic vitreous fibers indicate that greater 

potential for toxicity of inhaled inorganic fibers is associated with higher exposure concentrations, longer 

exposure durations, longer fiber lengths, greater fiber durability, and thinner fiber diameters. As 
SYNTHETIC VITREOUS FIBERS 17 

2. RELEVANCE TO PUBLIC HEALTH 

discussed in Sections 3.4 and 3.5, fiber dimensions influence several of these key determinants of toxicity 

including: 

•	 The amount of material deposited in the alveolar region of the lung (fibers with diameters >3 μm 

do not reach this region; they are deposited in the upper respiratory tract and lung conductive 

airways, cleared by mucociliary action to the pharynx, swallowed, and eliminated via the feces); 

•	 The rate at which macrophages engulf and clear fibers deposited in the lower lung (human 

macrophages cannot fully engulf fibers with lengths longer than about 15–20 μm); and 

•	 The extent of movement of deposited fibers from the alveoli to the lung interstitium and the 

pleural cavity (fibers with diameters >0.3–0.4 μm may move less freely into the interstitium and 

pleural cavity). 

Fibers that can dissolve in physiologic fluids (i.e., that are less durable) develop weak points that can 

facilitate (1) transverse breakage by physical forces into shorter fibers and (2) faster clearance by 

macrophages, compared with fibers that do not dissolve, like amphibole asbestos fibers. 

Synthetic vitreous fibers differ from asbestos in two ways that may provide at least partial explanations 

for their lower toxicity. Because most synthetic vitreous fibers are not crystalline like asbestos, they do 

not split longitudinally to form thinner fibers. They also generally have markedly less biopersistence in 

biological tissues than asbestos fibers because they can undergo dissolution and transverse breakage (see 

Sections 3.4 and 3.5). 

Irritation Effects. Occupational exposure to fibrous glass materials, including glass wool insulation and 

fiberglass fabrics, has been associated with acute skin irritation (“fiberglass itch”), eye irritation, and 

symptoms of upper respiratory tract irritation such as sore throat, nasal congestion, laryngeal pain, and 

cough. The skin irritation has been associated with glass wool fibers having diameters >5 μm and 

becomes less pronounced with continued exposure. Symptoms of irritation of the upper respiratory tract 

have been mostly associated with unusually dusty workplace conditions (concentrations >1 fiber/cc) 

involving removal of fibrous glass materials in closed spaces without respiratory protection. The 

symptoms have been reported to disappear shortly following cessation of exposure. Similar symptoms of 

dermal and upper respiratory irritation may also occur in workers involved in the manufacture, 

application, or removal of insulation materials containing refractory ceramic fibers, rock wool, or slag 

wool. 
SYNTHETIC VITREOUS FIBERS 18 

2. RELEVANCE TO PUBLIC HEALTH 

Cancer and Nonmalignant Respiratory Disease. Studies of workers predominantly involved in the 

manufacture of fibrous glass, rock wools, or slag wools have focused on the prevalence of respiratory 

symptoms through the administration of questionnaires, pulmonary function testing, and chest x-ray 

examinations. In general, these studies reported no consistent evidence for increased prevalence of 

adverse respiratory symptoms, abnormal pulmonary functions, or chest x-ray abnormalities; however, one 

study reported altered pulmonary function (decreased forced expiratory volume in 1 second) in a group of 

Danish insulation workers compared with a group of bus drivers. Longitudinal health evaluations of 

workers involved in the manufacture of refractory ceramic fibers have not found consistent evidence of 

exposure-related changes in chest x-rays or pulmonary functions, with the exception that pleural plaques 

were found in about 3% of examined U.S. refractory ceramic fiber manufacturing workers and that 

pleural plaque prevalence showed statistically significant trends with increasing exposure categories. 

Epidemiologic studies (cohort mortality and case-control studies) of causes of mortality among groups of 

workers involved in the manufacture of fibrous glass, rock wool, or slag wool provide no consistent 

evidence for increased risks of mortality from nonmalignant respiratory disease, lung cancer, or pleural 

mesothelioma. A number of reviews of these cohort mortality and case-control studies concur that the 

studies provide inadequate evidence for the carcinogenicity of synthetic vitreous fibers in humans. In an 

initial report of the only available cohort mortality study of refractory ceramic fiber manufacturing 

workers, the only statistically significant excess mortality was for deaths associated with cancer of the 

urinary system. No mesotheliomas and no excess deaths associated with respiratory cancers or 

nonmalignant respiratory disease were found. 

For all synthetic vitreous fibers tested, pulmonary inflammation has been observed in animals 

(predominately rodents) following intermediate- or chronic-duration inhalation exposure at concentrations 

more than an order of magnitude higher than 1 NIOSH fiber (length >5μm; aspect ratio ≥3:1)/cc. This 

concentration is the current occupational exposure limit for insulation wools recommended by the 

American Conference of Governmental Industrial Hygienists; for refractory ceramic fibers the limit is 

0.2 NIOSH fibers/cc. 

The most extensively studied refractory ceramic fiber, RCF1, caused minimal-to-mild pulmonary 

inflammation in rats and hamsters at concentrations as low as 26 WHO fibers (length >5 μm; diameter 

<3 μm; aspect ratio ≥3:1)/cc (36 total fibers with aspect ratios ≥3:1 per cc) at 3 months. The severity of 

inflammation increased with duration and exposure concentration, but the severity of inflammatory 
SYNTHETIC VITREOUS FIBERS 19 

2. RELEVANCE TO PUBLIC HEALTH 

lesions did not exceed a moderate rating of “3" in most rats (on a 0–5 grade scale where 0 was “normal” 

and 5 was “severe”) even with exposure for 24 months to a concentration of 187 WHO fibers/cc. The 

inflammation showed signs of regression after cessation of exposure. 

Other refractory ceramic fibers, RCF2, RCF3, and RCF4, caused minimal-to-mild pulmonary 

inflammation in rats at single exposure levels in the concentration range of 153–220 WHO fiber/cc. The 

insulation glass wool MMVF10 caused pulmonary inflammation at concentrations as low as 29 WHO 

fibers/cc in hamsters and rats. Other multiple-exposure tests in male rats have demonstrated the induction 

of minimal pulmonary inflammation from concentrations as low as 41 WHO fibers/cc of the glass wool, 

MMVF11, 34 WHO fibers/cc of the rock wool, MMVF21, and 30 WHO fibers/cc of the slag wool, 

MMVF22. Several of these studies also showed that signs of inflammation subsided to various degrees 

after cessation of exposure. 

Pulmonary inflammation has also been observed in single-concentration experiments in male rats 

following intermediate- or chronic-duration inhalation exposure to the newly developed high-temperature 

rock wool, MMVF34, at 291 WHO fibers/cc, the high-silica synthetic vitreous fiber, X607, at 180 WHO 

fibers/cc, the special-purpose 104E-glass fiber, at 1,022 WHO fibers/cc, and GB100R glass wool at 

2.2 mg/m3

 (fiber counts in air samples were not measured). Pulmonary inflammation also occurred in 

hamsters repeatedly exposed to the special-purpose durable glass fiber, MMVF33, at 310 WHO fibers/cc. 

An intermediate-duration study in male baboons reported that 1,122 NIOSH fibers/cc of 

C102/C104 blend fibrous glass induced pulmonary inflammation. The only study to report a noobserved-adverse-effect-level (NOAEL) for pulmonary inflammation (from chronic-duration exposure) 

exposed female Wistar rats to 252 WHO fibers/cc of Code 104/475 glass fiber for 12 months. 

Following intermediate- or chronic-duration inhalation exposure, pulmonary or pleural fibrosis has been 

observed: in rats exposed to several refractory ceramic fibers, RCF1, RCF2, RCF3, and RCF4, in the 

concentration range of 153–220 WHO fibers/cc; in hamsters exposed to the special-purpose durable glass 

fiber, MMVF33, at 310 WHO fibers/cc; in rats exposed to the insulation rock wool, MMVF21, at 

150 WHO fibers/cc; in rats exposed to the special-purpose 104E-glass fiber at 1,022 WHO fibers/cc; and 

in baboons exposed to C102/104 blend fibrous glass at 1,122 fibers/cc. Exposure-response relationships 

for pulmonary or pleural fibrosis are best described, among these “fibrotic” synthetic vitreous fibers, for 

the refractory ceramic fiber, RCF1. In rats exposed to RCF1 for up to 2 years, signs of irreversible 

pulmonary or pleural fibrosis were induced at concentrations >75 WHO fibers/cc, but not at 26 WHO 
SYNTHETIC VITREOUS FIBERS 20 

2. RELEVANCE TO PUBLIC HEALTH 

fibers/cc. In general, synthetic vitreous fibers that cause fibrosis are more biopersistent than those that do 

not. 

Synthetic vitreous fibers that have not induced pulmonary or pleural fibrosis in animals following 

intermediate- or chronic-duration inhalation exposure include the insulation glass wools, MMVF10 and 

MMVF11, at concentrations in the 232–339 WHO fibers/cc range, the slag wool, MMVF22, at 213 WHO 

fibers/cc, the high-temperature rock wool, MMVF34, at 291 WHO fibers/cc, and the high-silica synthetic 

vitreous fiber, X607, at 180 WHO fibers/cc. All of these studies involved rats. 

Chronic inhalation exposure of animals to several biopersistent synthetic vitreous fibers has been shown 

to induce lung tumors or mesothelioma, whereas several less biopersistent synthetic fibers have not 

induced tumorigenic responses in animals exposed by inhalation for chronic durations. In these 

experiments, statistically significant increases in lung tumor incidence (adenomas or carcinomas) have 

been accepted as evidence of a tumorigenic response, whereas any detection of a mesothelioma has been 

generally accepted as evidence for this relatively rare type of tumor. 

Tumorigenic responses in the lung or pleura were observed in hamsters and rats exposed to the refractory 

ceramic fiber, RCF1, at concentrations as low as 75 WHO fibers/cc, in rats exposed to RCF2, RCF3, or 

RCF4 at concentrations between 153 and 220 WHO fibers/cc, in hamsters exposed to the durable glass 

fiber, MMVF33, at 310 WHO fibers/cc, and in rats exposed to the special purpose 104E-glass fiber at 

1,022 WHO fibers/cc. The carcinogenic response to 104E-glass fiber in rats was observed after only 

1 year of exposure, in contrast to another special purpose glass fiber, 100/475, which did not induce 

cancer in rats exposed to 1,119 WHO fibers/cc for 1 year. 

No other synthetic vitreous fiber types have produced evidence of carcinogenicity in chronic inhalation 

animal testing. Neither increased lung tumor incidence or the presence of mesotheliomas were found in 

rats exposed for 2 years to: the insulation glass wools, MMVF10 or MMVF11 at 232 or 246 WHO 

fibers/cc; the insulation rock wool, MMVF21, at 243 WHO fibers/cc of; the slag wool, MMVF22, at 

213 WHO fibers/cc; the newly developed high-temperature rock wool, MMVF34, at 291 WHO fibers/cc; 

or the high-silica synthetic vitreous fiber, X607, at 180 WHO fibers/cc. Additionally, evidence for 

carcinogenic responses was not found in male hamsters exposed to MMVF10a at 339 WHO fibers. 

Although no tumors were found in male baboons exposed to 1,122 NIOSH fibers/cc of C102/C104 blend 

fibrous glass for 30 months, the study was limited by small study size (biopsies of only two animals). 
SYNTHETIC VITREOUS FIBERS 21 

2. RELEVANCE TO PUBLIC HEALTH 

Increased incidences of fibrosis or tumors (e.g., lung tumors, mesotheliomas, sarcomas, or abdominal 

cavity tumors) have been observed in studies of rodents exposed to glass wool, rock wool, slag wool, or 

refractory ceramic fibers by intratracheal instillation, by intrapleural implantation or injection, and by 

intraperitoneal injection. These lesions were not observed in a few studies involving intraperitoneal 

injection of continuous filament glass fibers. Most of these studies involve a single administration 

followed by observation periods up to 2 years. The relevance of these studies to human inhalation 

exposure is limited because of the high doses used, the bypassing of the natural defense systems of the 

nasal and upper respiratory system, and the overloading or lack (for intraperitoneal studies) of clearance 

mechanisms mediated by pulmonary macrophages. 

The U.S. Department of Health and Human Services, National Toxicology Program classified glass wool 

(respirable size) as reasonably anticipated to be a human carcinogen, based on sufficient evidence of 

carcinogenicity in experimental animals. This assessment was originally prepared in 1993–1994 for the 

7th Report on Carcinogens, but has not been updated since then in the 8th, 9th, or 10th Reports on 

Carcinogens. Continuous filament glass, rock wool, slag wool, or refractory ceramic fibers were not 

listed or assessed for carcinogenicity in the 7th, 8th, 9th, or 10th Report on Carcinogens. 

In 2001, IARC convened a scientific working group of 19 experts from 11 countries to review a new 

monograph on “man-made vitreous fibers” that replaced the previous IARC monograph on these 

materials. The new monograph and the working group concluded that epidemiologic studies published 

since the previous IARC assessment provide no evidence of increased risks of lung cancer or of 

mesothelioma from occupational exposure during the manufacture of man-made vitreous fibers and 

inadequate evidence overall of any excess cancer risk. IARC concluded that there was (1) sufficient 

evidence in experimental animals for the carcinogenicity of certain special purpose glass fibers and of 

refractory ceramic fibers; (2) limited evidence in experimental animals for the carcinogenicity of 

insulation glass wool, rock (stone) wool, and slag wool; and (3) inadequate evidence in experimental 

animals for the carcinogenicity of continuous glass filament and certain newly developed, less 

biopersistent fibers such as X-607 and MMVF34. Insulation glass wool, rock (stone) wool, slag wool, 

and continuous filament glass were classified in Group 3, not classifiable as to carcinogenicity to humans 

because of the inadequate evidence of carcinogenicity in humans and the relatively low biopersistence of 

these materials. In contrast, refractory ceramic fibers and certain special-purpose glass fibers (104E-glass 
 

SYNTHETIC VITREOUS FIBERS 22 

2. RELEVANCE TO PUBLIC HEALTH 

and 475 glass fibers) not used as insulating materials were classified in Group 2B, possibly carcinogenic 

to humans, because of their relatively high biopersistence. 

The U.S. EPA Integrated Risk Information System (IRIS) has not classified the potential carcinogenicity 

of glass wool, continuous filament glass, rock wool, or slag wool, but assigned refractory ceramic fibers 

to Group B2, probable human carcinogen, based on no data on carcinogenicity in humans and sufficient 

evidence of carcinogenicity in animal studies. Currently, EPA is developing a cancer assessment for 

refractory ceramic fibers based on the multiple-exposure chronic inhalation animal bioassays. The 

assessment is considering the development of quantitative inhalation unit risk estimates for refractory 

ceramic fibers based on the animal tumorigenic responses, but, as of June 2004, the assessment has not 

been released. 

2.3 MINIMAL RISK LEVELS 

Inhalation MRLs 

•	 A minimal risk level (MRL) of 0.03 WHO fibers/cc has been derived for chronic-duration 

inhalation exposure to refractory ceramic fibers 

The 2-year, multiple-exposure level inhalation bioassay of the refractory ceramic fiber, RCF1, in male 

Fischer 344 rats provides the best available data describing exposure-response relationships for 

nonneoplastic lesions in the lung and pleura from chronic inhalation exposure to refractory ceramic fibers 

(Mast et al. 1995a, 1995b). The study identifies pulmonary inflammation as the critical nonneoplastic end 

point of concern and identifies other more serious effects at the higher exposure levels (pulmonary and 

pleural fibrosis and cancer of the lung and pleura). Other studies of rats exposed to RCF1 by inhalation 

provide strong support for pulmonary inflammation as the critical end point (Bellman et al. 2001; Everitt 

et al. 1997; Gelzleichter et al. 1999; McConnell et al. 1995), as well as other animal inhalation studies of 

other refractory ceramic fibers (Mast et al. 1995a) and other synthetic vitreous fibers such as insulation 

glass wools, MMVF10 and MMVF11 (Hesterberg et al. 1993c; McConnell et al. 1999), slag wool 

MMVF22 (McConnell et al. 1994), and rock wool MMVF21 (McConnell et al. 1994). Chronic-duration 

MRLs for the other synthetic vitreous fibers with adequate rat exposure-response data (e.g., MMVF10, 

MMVF11, MMVF21, and MMVF22) were not derived because of the lack of fully developed lung 

deposition and clearance models for these materials to aid in cross-species extrapolation from rats to 

humans. 
SYNTHETIC VITREOUS FIBERS 23 

2. RELEVANCE TO PUBLIC HEALTH 

The MRL was derived using a benchmark dose modeling approach and a cross-species dosimetric scaling 

factor derived from lung deposition and clearance models for RCF1 fibers in rats and humans, which 

were developed by C.P. Yu (University of Buffalo) and colleagues (Maxim et al. 2003b; Yu et al. 1995a, 

1995b, 1996, 1997, 1998a, 1998b). There are distinct differences between laboratory animal species and 

humans in respiratory tract size and geometry, ventilation rates and pattern, and macrophage sizes that 

influence the retention (the net result of deposition and clearance) of fibers in the lung. The lung 

retention models for RCF1 in rats and humans incorporate many of these interspecies differences, and 

significantly decrease uncertainty in extrapolating doses from rats to humans. 

The approach (described more completely in Appendix A) involved the following steps. 

(1) Continuous-variable models in the EPA Benchmark Dose Software were fit to exposureresponse data for lung weight and scores for macrophage aggregation, bronchiolization, and 

collagen deposition at the bronchoalveolar junction in male Fischer 344 male rats exposed to 

RCF1 for 2 years. 

(2) The best-fitting model for each end point was used to calculate a benchmark concentration 

and a lower 95% confidence limit (BMCs and BMCLs in units of total fibers/cc) associated 

with a 10% increase in lung weight, compared with controls, or a mean minimal score of 1.0 

(on a 0–5 scale) for the lesion. 

(3) The point of departure for the MRL was selected as the BMCL associated with the most 

sensitive end point, the BMCL for macrophage aggregation (9 total fibers/cc). 

(4) The selected rat BMCL was converted to a human equivalent concentration 

(BMCLHEC=1 WHO fibers/cc) using a cross-species scaling factor, 0.07, derived from the 

lung deposition and clearance models developed for RCF1 in rats and humans. 

(5) The BMCLHEC for macrophage aggregation was divided by an uncertainty factor of 30 (3 for 

interspecies extrapolation with dosimetric adjustment and 10 for human variability). 

The rat BMCL for pulmonary macrophage aggregation was selected as the point of departure for the 

MRL from the set of rat BMCLs for different pulmonary end points shown in Table 2-1. The ATSDR 

MRL Workgroup considered an alternative MRL derivation with bronchoalveolar collagen deposition as 

the critical effect, but preferred selection of macrophage aggregation as the critical effect because this 

effect occurred at lower concentrations than the other effects, as evidenced by the values of the rat BMCs 

and BMCLs in Table 2-1. When collagen deposition was selected as the critical effect for the MRL, an 

alternative MRL of 0.02 WHO fibers/cc was derived, which is similar in value to the MRL based on 
SYNTHETIC VITREOUS FIBERS 24 

2. RELEVANCE TO PUBLIC HEALTH 

Table 2-1. BMCs and BMCLs for 10% Lung Weight Increase and Pulmonary
 

Lesion Scores of 1 in Rats Exposed to RCF1 for 24 Months 

Endpoint BMC (total fiber/cc) BMCL (total fiber/cc) 

Lung weight 133 79 

Pulmonary macrophage aggregation 12 9 

Bronchiolization 37 30 

Collagen deposition at the bronchoalveolar junction 37 32 

Source: Mast et al. 1995a, 1995b; see text and Appendix A for more details on the benchmark dose analysis. 
 

SYNTHETIC VITREOUS FIBERS 25 

2. RELEVANCE TO PUBLIC HEALTH 

macrophage aggregation (0.03 WHO fibers/cc). (The alternative MRL used a rat benchmark 

concentration of 32 total fibers/cc, a cross-species scaling factor of 0.07, and a total uncertainty factor 

of 90: 3 for cross-species extrapolation, 10 for human variability, and 3 for the selection of a potentially 

serious adverse effect as the critical effect; see Appendix A.) 

The rat BMCs and BMCLs shown in Table 2-1 were calculated from the best-fitting models for the 

exposure-response data for the most sensitive nonneoplastic pulmonary effects observed in Fischer 

344 rats and shown in Table 2-2. The data in Table 2-2 show that each of these effects increased in 

severity with increasing exposure level. The severity of each of these effects also was positively related 

with concentrations of fibers in the lungs of the rats following 24 months of exposure (see Table 2-2). 

Although the 2-year RCF1 bioassays (Mast et al. 1995a, 1995b) provide the best available exposureresponse data for refractory ceramic fibers, the presence of nonfibrous particles in the RCF1 test 

atmosphere is widely acknowledged to have added to the lung responses in rats to an undetermined 

degree (Bellmann et al. 2001; Mast et al. 2000; Maxim et al. 2003b). Under conditions in which lung 

clearance mechanisms become overloaded, many types of nonfibrous or fibrous materials can produce 

pulmonary fibrosis or tumors in rats (Oberdörster 1994). The ratio of total fibers:nonfibrous particles for 

the RCF1 material used in the 2-year rat bioassay has been reported to be about 3:1 by Bellmann et al. 

(2001), about 1–2:1 from data reported by Mast et al. (1995a, 1995b), and 9:1 by Maxim et al. (1997). In 

contrast, workplace air samples showed a ratio of about 0.5:1 (Maxim et al. 1997). The likelihood that 

the nonfibrous particles in the RCF1 material contributed, to an undetermined degree, to the lung 

responses in rat indicates that the MRL may underestimate the daily human exposure that is likely to be 

without appreciable risk of adverse noncancer health effects. As such, the MRL is expected to be 

protective of public health. 

Some evidence that the presence of the nonfibrous particles can enhance the effects on the lung was 

provided by comparing responses in rats exposed by inhalation for 3 weeks to concentrations of about 

125 fibers (with lengths >20 μm)/cc of either RCF1 or a sample of refractory ceramic fiber, called 

RCF1a, in which only 2% of the mass was accounted for by nonfibrous particles (Bellmann et al. 2001). 

Expressed as WHO fibers/cc, the mean concentrations were 481 fibers/cc for RCF1a and 679 fibers/cc for 

RCF1. Pulmonary clearance ability was markedly depressed by RCF1, but not by RCF1a, and indices of 

pulmonary inflammation were more persistently increased by RCF1 than by RCF1a (Bellmann et al. 

2001). 
SYNTHETIC VITREOUS FIBERS 26 

2. RELEVANCE TO PUBLIC HEALTH 

Table 2-2. Non-neoplastic Lung Responses in F344 Rats Exposed for 

24 Months to RCF1 

Fiber concentrations in Mean score±standard deviation (0–5 Scale) 

Exposure 

level (total 

fibers/cc) 

lungs at 24 months 

(mean total fibers per 

mg lung x104

) 

Lung weight 

(Percent of 

control) 

Macrophage 

aggregation 

Bronchiolization 

Collagen deposition 

at the bronchoalveolar junction 

0 (n=12) NR 100.0±14.0 0±0 0±0 0±0 

36 (n=6) 5.55±1.71 116.8±12.3 2.0±0 1.2±0.4 0.7±0.82 

91 (n=6) 18.80±3.59 110.9±8.1 2.5±0.6 1.8±0.4 2±0 

162 (n=6) 27.80±6.06 131.8±15.3 3.0±0 2.7±0.5 2.8±0.4 

234 (n=6) 37.00±8.01 164.7±44.2 3.2±0.4 2.7±0.5 2.2±0.4 

Source: Mast et al. 1995a, 1995b; Bernstein et al. 2001b; see Appendix A 

0–5 Scale: 0=normal; 1=minimal; 2=mild; 3=moderate; 4=marked; 5=severe; NR= not reported 
SYNTHETIC VITREOUS FIBERS 27 

2. RELEVANCE TO PUBLIC HEALTH 

The chronic MRL is expected to be appropriately applied to intermediate-duration exposure scenarios, 

based on evidence from interim sacrifice data from the Mast et al. (1995a, 1995b) bioassay that exposureresponse relationships for pulmonary inflammation and chronic exposure are similar to those for 

intermediate-duration exposure. Scores for pulmonary inflammation progressed to only a limited degree 

with progression from intermediate to chronic duration. For example, mean scores for macrophage 

aggregation in rats exposed to 3, 9, 16, and 30 mg/m3

 at 3 months were 1.7, 2, 2, and 2, respectively. The 

respective scores were 2, 2.3, 3, and 3 at 24 months and 2, 2.5, 3, and 3.2 at 24 months. 

Exposure-response relationships for pulmonary inflammation from acute inhalation exposure to synthetic 

vitreous fibers are inadequately characterized for deriving an acute inhalation MRL for any type of 

synthetic vitreous fiber. 

Any use of the MRL for refractory ceramic fibers in assessing likely health hazards from the insulation 

wools should acknowledge the evidence that many of the insulation wools are markedly less durable and 

less potent than refractory ceramic fibers (Bernstein et al. 2001a, 2001b; Eastes and Hadley 1996; Eastes 

et al. 2000; Hesterberg et al. 1998a). There are data from multiple-exposure-level 2-year rat inhalation 

bioassays on the glass wools, MMVF10 and MMVF11 (Hesterberg et al. 1993c; McConnell et al. 1999), 

the slag wool, MMVF22 (McConnell et al. 1994), and the rock wool, MMVF21 (McConnell et al. 1994) 

that adequately describe exposure-response relationships for nonneoplastic pulmonary effects (i.e., 

pulmonary inflammation) from intermediate- and chronic-duration exposure to these materials. However, 

lung deposition and clearance models for these synthetic vitreous fibers (such as the ones developed by 

C.P. Yu and colleagues for RCF1) are not yet fully developed to carry out physiologically based 

dosimetric calculations of human equivalent concentrations. 

There are no adequate data (from multiple-exposure level studies) for deriving inhalation MRLs for the 

other types of synthetic vitreous fibers (special applications glass fibers or continuous filament glass 

fibers that are woven). 

Oral MRLs 

No MRLs were derived for oral exposure to any synthetic vitreous fibers for any duration of exposure. 

No studies were located regarding noncancer health effects in humans or animals orally exposed to 

synthetic vitreous fibers. Oral exposure to synthetic vitreous fibers does not present a high priority public 
SYNTHETIC VITREOUS FIBERS 28 

2. RELEVANCE TO PUBLIC HEALTH 

health concern, given the low probability of exposure by this route. Supporting the lack of concern, 

results from an extensive series of lifetime studies of asbestos fibers in the diet of rats and hamsters found 

no consistent evidence for increased nonneoplastic lesions in exposed compared with control animals (see 

Agency for Toxic Substance and Disease Registry 2001). 
SYNTHETIC VITREOUS FIBERS 29 

3. HEALTH EFFECTS 

3.1 INTRODUCTION 

The primary purpose of this chapter is to provide public health officials, physicians, toxicologists, and 

other interested individuals and groups with an overall perspective on the toxicology of synthetic vitreous 

fibers. It contains descriptions and evaluations of toxicological studies and epidemiological 

investigations and provides conclusions, where possible, on the relevance of toxicity and toxicokinetic 

data to public health. 

A glossary and list of acronyms, abbreviations, and symbols can be found at the end of this profile. 

3.2 DISCUSSION OF HEALTH EFFECTS BY ROUTE OF EXPOSURE 

To help public health professionals and others address the needs of persons living or working near 

hazardous waste sites, the information in this section is organized first by route of exposure (inhalation, 

oral, and dermal) and then by health effect (death, systemic, immunological, neurological, reproductive, 

developmental, genotoxic, and carcinogenic effects). These data are discussed in terms of three exposure 

periods: acute (14 days or less), intermediate (15–364 days), and chronic (365 days or more). 

Levels of significant exposure for each route and duration are presented in tables and illustrated in 

figures. The points in the figures showing no-observed-adverse-effect levels (NOAELs) or lowestobserved-adverse-effect levels (LOAELs) reflect the actual doses (levels of exposure) used in the studies. 

LOAELs have been classified into "less serious" or "serious" effects. "Serious" effects are those that 

evoke failure in a biological system and can lead to morbidity or mortality (e.g., acute respiratory distress 

or death). "Less serious" effects are those that are not expected to cause significant dysfunction or death, 

or those whose significance to the organism is not entirely clear. ATSDR acknowledges that a 

considerable amount of judgment may be required in establishing whether an end point should be 

classified as a NOAEL, "less serious" LOAEL, or "serious" LOAEL, and that in some cases, there will be 

insufficient data to decide whether the effect is indicative of significant dysfunction. However, the 

Agency has established guidelines and policies that are used to classify these end points. ATSDR 

believes that there is sufficient merit in this approach to warrant an attempt at distinguishing between 
SYNTHETIC VITREOUS FIBERS 30 

3. HEALTH EFFECTS 

"less serious" and "serious" effects. The distinction between "less serious" effects and "serious" effects is 

considered to be important because it helps the users of the profiles to identify levels of exposure at which 

major health effects start to appear. LOAELs or NOAELs should also help in determining whether or not 

the effects vary with dose and/or duration, and place into perspective the possible significance of these 

effects to human health. 

The significance of the exposure levels shown in the Levels of Significant Exposure (LSE) tables and 

figures may differ depending on the user's perspective. Public health officials and others concerned with 

appropriate actions to take at hazardous waste sites may want information on levels of exposure 

associated with more subtle effects in humans or animals (LOAELs) or exposure levels below which no 

adverse effects (NOAELs) have been observed. Estimates of levels posing minimal risk to humans 

(Minimal Risk Levels or MRLs) may be of interest to health professionals and citizens alike. 

Estimates of exposure levels posing minimal risk to humans (Minimal Risk Levels or MRLs) have been 

made for synthetic vitreous fibers. An MRL is defined as an estimate of daily human exposure to a 

substance that is likely to be without an appreciable risk of adverse effects (noncarcinogenic) over a 

specified duration of exposure. MRLs are derived when reliable and sufficient data exist to identify the 

target organ(s) of effect or the most sensitive health effect(s) for a specific duration within a given route 

of exposure. MRLs are based on noncancerous health effects only and do not consider carcinogenic 

effects. MRLs can be derived for acute, intermediate, and chronic duration exposures for inhalation and 

oral routes. Appropriate methodology does not exist to develop MRLs for dermal exposure. 

Although methods have been established to derive these levels (Barnes and Dourson 1988; EPA 1990), 

uncertainties are associated with these techniques. Furthermore, ATSDR acknowledges additional 

uncertainties inherent in the application of the procedures to derive less than lifetime MRLs. As an 

example, acute inhalation MRLs may not be protective for health effects that are delayed in development 

or are acquired following repeated acute insults, such as hypersensitivity reactions, asthma, or chronic 

bronchitis. As these kinds of health effects data become available and methods to assess levels of 

significant human exposure improve, these MRLs will be revised. 

A User's Guide has been provided at the end of this profile (see Appendix B). This guide should aid in 

the interpretation of the tables and figures for Levels of Significant Exposure and the MRLs. 
SYNTHETIC VITREOUS FIBERS 31 

3. HEALTH EFFECTS 

3.2.1 Inhalation Exposure 

3.2.1.1 Death 

No studies were located in which acute- or intermediate-duration inhalation exposure to synthetic vitreous 

fibers caused mortality in humans. As discussed in Sections 3.2.1.2 and 3.2.1.7, cohort mortality studies 

of workers involved in the manufacture of fiberglass, rock wool, slag wool, and refractory ceramic fibers 

have not found consistently increased risk of mortality associated with nonmalignant or malignant 

respiratory disease. 

None of the animal studies described below observed increased risk of death after inhalation exposure to 

synthetic vitreous fibers. 

3.2.1.2 Systemic Effects 

No studies were located regarding hematological, musculoskeletal, endocrine, dermal, ocular, or body 

weight effects in humans or animals after inhalation exposure to synthetic vitreous fibers. The principal 

target organ of inhaled synthetic vitreous fibers is the respiratory system. 

The highest NOAEL values and all LOAEL values from each reliable study for systemic effects from 

inhalation exposure to synthetic vitreous fibers are summarized in Table 3-1 and plotted in Figure 3-1. 

Although there are epidemiological studies of workers involved in the manufacture of synthetic vitreous 

fibers such as refractory ceramic fibers, the results do not characterize exposure-response relationships for 

potential health effects in humans. In contrast, animal inhalation studies identify several types of 

respiratory effects from various types of synthetic vitreous fibers and provide information on exposureresponse relationships. Thus, data in Table 3-1 and Figure 3-1 are restricted to reliable NOAEL and 

LOAEL values from animal inhalation toxicity studies. Units of exposure in animal studies include 

gravimetric measurements (mg/m3

), which include the weight of nonfibrous particles present in air 

samples, and fiber count measurements (# fibers/cc), which rely on microscopically aided counting of 

fiber numbers in air samples. The most frequently reported unit of exposure among the available animal 

toxicity studies is based on the WHO fiber counting rules (i.e., a fiber is counted as a particle with length 
1

1700

2

2645

3

1700

38

679

42

481

Table 3-1 Levels of Significant Exposure to Synthetic Vitreous Fibers - Inhalation 

Exposure/ LOAEL

Duration/

a

Key to Species Frequency NOAEL Less Serious Serious 

(Specific Route) figure (Strain) System (WHO fibers/cc) (WHO fibers/cc) (WHO fibers/cc) 

ACUTE EXPOSURE Systemic 

1 Rat 5 d b 

6 hr/d Resp 1700 M (pulmonary and pleural (Fischer- 344) 

inflammation; increased lung (nose only) and diaphragm mesothelial cell proliferation) 

2 Rat 5 d 

Resp 2645 M (pulmonary and pleural (Fischer- 344) 6 hr/d inflammation) 

3 Hamster 5 d b 

6 hr/d Resp 1700 M (pulmonary and pleural (Golden 

inflammation; increased lung Syrian) (nose only) mesothelial cell proliferation) 

INTERMEDIATE EXPOSURE Systemic 

4 Rat 3 wk 

Resp 679 F (very slight interstitial fibrosis, 6 hr/day (Wistar) pulmonary inflammation, 

5 d/wk 

reduced alveolar clearance) (nose only) 

5 Rat 3 wk 

Resp 481 F (very slight interstitial fibrosis, 6 hr/day (Wistar) pulmonary inflammation) 

5 d/wk (nose only) 
Table 3-1 Levels of Significant Exposure to Synthetic Vitreous Fibers - Inhalation (continued) 

Exposure/ LOAEL 

Duration/ a Frequency 

Key to Species NOAEL Less Serious Serious (Specific Route) figure (Strain) System (WHO fibers/cc) (WHO fibers/cc) (WHO fibers/cc) 

6 Rat 1 yr 

7 hr/d Resp 1119 M (pulmonary inflammation) (Wistar) 

5 d/wk 1119 

1021

7 Rat 1 yr 

Resp 1022 M (advanced pulmonary fibrosis; 7 hr/d (Wistar) pulmonary inflammation) 

5 d/wk 

1022 

4

8 Rat 4 wk 

Resp 4 hr/d 300 M (pulmonary and pleural (Fischer- 344) 

5 d/wk inflammation; incr. lung and 

diaphragm mesothelial cell (nose only) proliferation) 

300

32

9 Rat 12 wk 

Resp 4 hr/d 300 M (pulmonary and pleural (Fischer- 344) 

5 d/wk inflammation; incr. lung and 

diaphragm mesothelial cell (nose only) proliferation) 

300

39

10 Rat 12 wk 

4 hr/d Resp 296 M (pulmonary and pleural (Fischer- 344) 

5d/wk inflammation) 

296

34
10

29

232

11

29

232

12

29

232

16

41

246

Table 3-1 Levels of Significant Exposure to Synthetic Vitreous Fibers - Inhalation (continued) 

a

Key to Species 

figure (Strain) 

11 

(Fischer- 344) Rat 

12 

(Fischer- 344) Rat 

13 

(Fischer- 344) Rat 

14 

(Fischer- 344) Rat 

Exposure/ 

Duration/ 

Frequency 

(Specific Route) 

3 mo 6 hr/d 5 d/wk (nose only) 6 mo 6 hr/d 5 d/wk (nose only) 12 mo 6 hr/d 5 d/wk (nose only) 3 mo 6 hr/d 5 d/wk (nose only) 

System 

Resp Bd Wt Resp Bd Wt Resp Bd Wt Resp Bd Wt 

NOAEL

(WHO fibers/cc)

232 M 232 M 232 M 246 M 

LOAEL 

Less Serious 

(WHO fibers/cc) 

29 M (minimal pulmonary

inflammation)

29 M (minimal-to-mild pulmonary 

inflammation) 

29 M (minimal-to-mild pulmonary 

inflammation) 

41 M (minimal pulmonary

inflammation)

Serious 

(WHO fibers/cc) 
17

41

256

18

41

246

55

180

180180180

Table 3-1 Levels of Significant Exposure to Synthetic Vitreous Fibers - Inhalation (continued) 

Exposure/ 

Duration/

a

Key to Species Frequency 

figure (Strain) (Specific Route) 

15 Rat 6 mo 

6 hr/d (Fischer- 344) 5 d/wk (nose only) 

16 Rat 12 mo 

6 hr/d (Fischer- 344) 5 d/wk (nose only) 

17 Rat 3 mo 

6 hr/d (Fischer- 344) 5 d/wk (nose only) 

System 

Resp Bd Wt Resp Bd Wt Resp Hepatic Renal Bd Wt 

NOAEL

(WHO fibers/cc)

256 M 246 M 180 M 180 M 180 M 

Less Serious 

(WHO fibers/cc) 

41 M (minimal-to-mild pulmonary 

inflammation) 

41 M (minimal-to-mild pulmonary 

inflammation) 

180 M (pulmonary inflammation) 

Serious 

(WHO fibers/cc) 

LOAEL 
56

180

180180180

57

180

180180180

Table 3-1 Levels of Significant Exposure to Synthetic Vitreous Fibers - Inhalation (continued) 

Exposure/ LOAEL 

a

Key to 

figure 

Duration/ 

Frequency 

(Specific Route) Species (Strain) NOAEL System (WHO fibers/cc) 

18 6 mo 

6 hr/d 5 d/wk (nose only) 

(Fischer- 344) Rat 

Resp Hepatic 180 M Renal 180 M Bd Wt 180 M 

19 1 yr 

6 hr/d 5 d/wk (nose only) 

(Fischer- 344) Rat 

Resp Hepatic 180 M Renal 180 M Bd Wt 180 M 

Less Serious 

(WHO fibers/cc) 

Serious 

(WHO fibers/cc) 

180 M (pulmonary inflammation) 180 M (pulmonary inflammation) 
28

291

291

29

291

291

30

291

291

Table 3-1 Levels of Significant Exposure to Synthetic Vitreous Fibers - Inhalation (continued) 

a

Key to 

figure 

Species 

(Strain) 

Exposure/ 

Duration/ 

Frequency 

(Specific Route) System 

NOAEL 

(WHO fibers/cc) 

Less Serious 

(WHO fibers/cc) 

LOAEL 

Serious 

(WHO fibers/cc) 

20 3 mo 

6 hr/d 5 d/wk (nose only) 

(Fischer- 344) Rat 

Resp 291 M (minimal pulmonary 

inflammation) 

Bd Wt 291 M 

21 6 mo 

6 hr/d 5 d/wk (nose only) 

(Fischer- 344) Rat 

Resp 291 M (minimal-to-slight pulmonary 

inflammation; bronchoalveolar collagen deposition without fibrosis) 

Bd Wt 291 M 

22 12 mo 

6 hr/d 5 d/wk (nose only) 

(Fischer- 344) Rat 

Resp 291 M (minimal-to-slight pulmonary 

inflammation) 

Bd Wt 291 M 
43

220

220220220220

44

220

220220220220

Table 3-1 Levels of Significant Exposure to Synthetic Vitreous Fibers - Inhalation (continued) 

Exposure/ 

Duration/

a

Key to Species Frequency 

figure (Strain) (Specific Route) 

23 Rat 3 mo 

6 hr/d (Fischer- 344) 5 d/wk (nose only) 

24 Rat 6 mo 

6 hr/d (Fischer- 344) 5 d/wk (nose only) 

System 

Resp Cardio Hepatic Renal Bd Wt Resp Cardio Hepatic Renal Bd Wt 

LOAEL 

NOAEL 

(WHO fibers/cc) 

Less Serious 

(WHO fibers/cc) 

Serious 

(WHO fibers/cc) 

220 M (minimal-to-mild pulmonary 

inflammation) 

220 M 220 M 220 M 220 M 

220 M (minimal-to-mild pulmonary 

inflammation) 

220 M 220 M 220 M 220 M 
45

220

220220220220

46

220

220220220220

Table 3-1 Levels of Significant Exposure to Synthetic Vitreous Fibers - Inhalation (continued) 

Exposure/ 

Duration/

a

Key to Species Frequency 

figure (Strain) (Specific Route) 

25 Rat 9 mo 

6 hr/d (Fischer- 344) 5 d/wk (nose only) 

26 Rat 12 mo 

6 hr/d (Fischer- 344) 5 d/wk (nose only) 

System 

Resp Cardio Hepatic Renal Bd Wt Resp Cardio Hepatic Renal Bd Wt 

LOAEL 

NOAEL 

(WHO fibers/cc) 

Less Serious 

(WHO fibers/cc) 

Serious 

(WHO fibers/cc) 

220 M (minimal-to-mild interstitial 

fibrosis, minimal pleural fibrosispulmonary inflammation) 

220 M 220 M 220 M 220 M 

220 M (mild interstitial fibrosis, 

pulmonary inflammation) 

220 M 220 M 220 M 220 M 
47

182

182182182182

48

182

182182182182

Table 3-1 Levels of Significant Exposure to Synthetic Vitreous Fibers - Inhalation (continued) 

a

Key to 

figure 

Species 

(Strain) 

Exposure/ 

Duration/ 

Frequency 

(Specific Route) System 

NOAEL 

(WHO fibers/cc) 

Less Serious 

(WHO fibers/cc) 

LOAEL 

Serious 

(WHO fibers/cc) 

27 3 mo 

6 hr/d 5 d/wk (nose only) 

(Fischer- 344) Rat 

Resp 182 M (minimal-to-mild pulmonary 

inflammation) 

Cardio 182 M Hepatic Renal 

182 M 182 M 

Bd Wt 182 M 

28 6 mo 

6 hr/d 5 d/wk (nose only) 

(Fischer- 344) Rat 

Resp 182 M (minimal-to-mild interstitial 

fibrosis, pulmonary inflammation) 

Cardio 182 M Hepatic Renal 

182 M 182 M 

Bd Wt 182 M 
49

182

182182182182

50

182

182182182182

Table 3-1 Levels of Significant Exposure to Synthetic Vitreous Fibers - Inhalation (continued) 

Exposure/ 

Duration/

a

Key to Species Frequency 

figure (Strain) (Specific Route) 

29 Rat 9 mo 

6 hr/d (Fischer- 344) 5 d/wk (nose only) 

30 Rat 12 mo 

6 hr/d (Fischer- 344) 5 d/wk (nose only) 

System 

Resp Cardio Hepatic Renal Bd Wt Resp Cardio Hepatic Renal Bd Wt 

LOAEL 

NOAEL Less Serious

(WHO fibers/cc) (WHO fibers/cc) 

Serious 

(WHO fibers/cc) 

182 M (mild interstitial fibrosis, 

minimal-to-mild pleural fibrosis, pulmonary inflammation) 

182 M 182 M 182 M 182 M 

182 M (mild-to-moderate interstitial 

fibrosis, minimal-to-mild pleural fibrosis, pulmonary inflammation) 

182 M 182 M 182 M 182 M 
51

153

153153153153

52

153

153153153153

Table 3-1 Levels of Significant Exposure to Synthetic Vitreous Fibers - Inhalation (continued) 

Exposure/ 

Duration/

a

Key to Species Frequency 

figure (Strain) (Specific Route) 

31 Rat 3 mo 

6 hr/d (Fischer- 344) 5 d/wk (nose only) 

32 Rat 6 mo 

6 hr/d (Fischer- 344) 5 d/wk (nose only) 

System 

Resp Cardio Hepatic Renal Bd Wt Resp Cardio Hepatic Renal Bd Wt 

LOAEL 

NOAEL 

(WHO fibers/cc) 

Less Serious 

(WHO fibers/cc) 

Serious 

(WHO fibers/cc) 

153 M (minimal-to-mild pulmonary 

inflammation) 

153 M 153 M 153 M 153 M 

153 M (minimal-to-mild pulmonary 

inflammation) 

153 M 153 M 153 M 153 M 
53

153

153153153153

54

153

153153153153

Table 3-1 Levels of Significant Exposure to Synthetic Vitreous Fibers - Inhalation (continued) 

a

Key to 

figure 

Species 

(Strain) 

Exposure/ 

Duration/ 

Frequency 

(Specific Route) System 

NOAEL 

(WHO fibers/cc) 

Less Serious 

(WHO fibers/cc) 

LOAEL 

Serious 

(WHO fibers/cc) 

33 9 mo 

6 hr/d 5 d/wk (nose only) 

(Fischer- 344) Rat 

Resp 153 M (minimal-to-mild pulmonary 

inflammation) 

Cardio 153 M Hepatic Renal 

153 M 153 M 

Bd Wt 153 M 

34 12 mo 

6 hr/d 5 d/wk (nose only) 

(Fischer- 344) Rat 

Resp 153 M (minimal-to-mild interstitial 

fibrosis, pulmonary inflammation) 

Cardio 153 M Hepatic Renal 

153 M 153 M 

Bd Wt 153 M 
31

26

187187187187

37

26

187

187187187187

Table 3-1 Levels of Significant Exposure to Synthetic Vitreous Fibers - Inhalation (continued) 

a

Key to 

figure 

Species 

(Strain) 

Exposure/ 

Duration/ 

Frequency 

(Specific Route) System 

NOAEL 

(WHO fibers/cc) 

Less Serious 

(WHO fibers/cc) 

LOAEL 

Serious 

(WHO fibers/cc) 

35 3 mo 

6 hr/d 5 d/wk (nose only) 

(Fischer- 344) Rat 

Resp 26 M (minimal-to-mild pulmonary 

inflammation) 

Cardio 187 M Hepatic Renal 

187 M 187 M 

Bd Wt 187 M 

36 6 mo 

6 hr/d 5 d/wk (nose only) 

(Fischer- 344) Rat 

Resp 26 M (minimal-to-mild pulmonary 

inflammation) 

187 M (minimal-to-mild interstitial 

fibrosis, pulmonary inflammation) 

Cardio 187 M Hepatic Renal 

187 M 187 M 

Bd Wt 187 M 
41

36 91

234234234234

19

34

243243243243

Table 3-1 Levels of Significant Exposure to Synthetic Vitreous Fibers - Inhalation (continued) 

a

Key to 

figure 

Species 

(Strain) 

Exposure/ 

Duration/ 

Frequency 

(Specific Route) System 

NOAEL 

(WHO fibers/cc) 

Less Serious 

(WHO fibers/cc) 

LOAEL 

Serious 

(WHO fibers/cc) 

37 12 mo 

6 hr/d 5 d/wk (nose only) 

(Fischer- 344) Rat 

Resp 36 M (minimal-to-mild pulmonary 

inflammation) 

91 M (minimal-to-mild interstitial 

fibrosis) 

Cardio 234 M Hepatic 234 M Renal 234 M Bd Wt 234 M 

38 3 mo 

6 hr/d 5 d/wk (nose only) 

(Fischer- 344) Rat 

Resp 34 M (pulmonary inflammation) 

Cardio 243 M Hepatic 243 M Renal 243 M Bd Wt 243 M 
20

34

243243243243

21

34

243243243243

Table 3-1 Levels of Significant Exposure to Synthetic Vitreous Fibers - Inhalation (continued) 

Exposure/ 

Duration/

a

Key to Species Frequency 

figure (Strain) (Specific Route) 

39 Rat 6 mo 

6 hr/d (Fischer- 344) 5 d/wk (nose only) 

40 Rat 12 mo 

6 hr/d (Fischer- 344) 5 d/wk (nose only) 

System 

Resp Cardio Hepatic Renal Bd Wt Resp Cardio Hepatic Renal Bd Wt 

LOAEL 

NOAEL 

(WHO fibers/cc) 

Less Serious 

(WHO fibers/cc) 

Serious 

(WHO fibers/cc) 

34 M (pulmonary inflammation) 

243 M 243 M 243 M 243 M 

34 M (pulmonary inflammation) 

243 M 243 M 243 M 243 M 
22

30

213213213213

23

30

213213213213

Table 3-1 Levels of Significant Exposure to Synthetic Vitreous Fibers - Inhalation (continued) 

Exposure/ 

Duration/

a

Key to Species Frequency 

figure (Strain) (Specific Route) 

41 Rat 3 mo 

6 hr/d (Fischer- 344) 5 d/wk (nose only) 

42 Rat 6 mo 

6 hr/d (Fischer- 344) 5 d/wk (nose only) 

System 

Resp Cardio Hepatic Renal Bd Wt Resp Cardio Hepatic Renal Bd Wt 

LOAEL 

NOAEL 

(WHO fibers/cc) 

Less Serious 

(WHO fibers/cc) 

Serious 

(WHO fibers/cc) 

30 M (pulmonary inflammation) 

213 M 213 M 213 M 213 M 

30 M (pulmonary inflammation) 

213 M 213 M 213 M 213 M 
24

30

213213213213252

633

300

Table 3-1 Levels of Significant Exposure to Synthetic Vitreous Fibers - Inhalation (continued) 

a

Key to Species 

figure (Strain) 

43 Rat 

(Fischer- 344) 

44 Rat 

(Wistar) 

45 Hamster 

(Golden Syrian) 

Exposure/ 

Duration/ 

Frequency 

(Specific Route) System 

NOAEL 

(WHO fibers/cc) 

Less Serious 

(WHO fibers/cc) 

LOAEL 

Serious 

(WHO fibers/cc) 

12 mo 6 hr/d 5 d/wk (nose only) 

Resp 30 M (pulmonary inflammation) 

Cardio 213 M Hepatic 213 M Renal 213 M Bd Wt 213 M 

12 mo 5 hr/d 4 d/wk (nose only) 

Resp 252 

4 wk 4 hr/d 5 d/wk (nose only) 

Resp 300 M (pulmonary and pleural 

inflammation; incr. lung and diaphragm mesothelial cell proliferation) 
40

300

35

296

12

316

9

36

Table 3-1 Levels of Significant Exposure to Synthetic Vitreous Fibers - Inhalation (continued) 

a

Key to Species 

figure (Strain) 

46 Hamster 

(Golden Syrian) 

47 Hamster 

(Golden Syrian) 

48 Hamster 

(Golden Syrian) 

49 Hamster 

(Golden Syrian) 

Exposure/ 

Duration/ 

Frequency 

(Specific Route) System 

NOAEL 

(WHO fibers/cc) 

Less Serious 

(WHO fibers/cc) 

LOAEL 

Serious 

(WHO fibers/cc) 

12 wk 4 hr/d 5 d/wk (nose only) 

Resp 300 M (pulmonary and pleural 

inflammation; incr. lung and diaphragm mesothelial cell proliferation; early signs of pleural fibrosis) 

12 wk 4 hr/d 5d/wk 

Resp 296 M (pulmonary and pleural 

inflammation) 

7 wk 6 hr/d 5 d/wk (nose only) 

Resp 316 M (pulmonary inflammation) 

13 wk 6 hr/d 5 d/wk (nose only) 

Resp 36 M (pulmonary inflammation) 
36

215

215215215215

13

339

339

14

339

339

Table 3-1 Levels of Significant Exposure to Synthetic Vitreous Fibers - Inhalation (continued) 

a

Key to Species 

figure (Strain) 

50 Hamster 

(Golden Syrian) 

51 Hamster 

(Golden Syrian) 

52 Hamster 

(Golden Syrian) 

Exposure/ 

Duration/ 

Frequency 

(Specific Route) 

3 mo 5 d/wk 6 hr/d (nose only) 3 mo 6 hr/d 5 d/wk (nose only) 6 mo 6 hr/d 5 d/wk (nose only) 

System 

Resp Cardio Hepatic Renal Bd Wt Resp Bd Wt Resp Bd Wt 

NOAEL

(WHO fibers/cc)

215 M 215 M 215 M 215 M 339 M 339 M 

LOAEL 

Less Serious 

(WHO fibers/cc) 

215 M (mild-to-moderate pulmonary 

inflammation) 

339 M (minimal-to-moderate

pulmonary inflammation)

339 M (minimal-to-mild pulmonary 

inflammation) 

Serious 

(WHO fibers/cc) 
15

339

339

25

310

310

26

310

310

Table 3-1 Levels of Significant Exposure to Synthetic Vitreous Fibers - Inhalation (continued) 

a

Key to Species 

figure (Strain) 

53 Hamster 

(Golden Syrian) 

54 Hamster 

(Golden Syrian) 

55 Hamster 

(Golden Syrian) 

Exposure/ 

Duration/ 

Frequency 

(Specific Route) 

12 mo 6 hr/d 5 d/wk (nose only) 3 mo 6 hr/d 5 d/wk (nose only) 6 mo 6 hr/d 5 d/wk (nose only) 

System 

Resp Bd Wt Resp Bd Wt Resp Bd Wt 

NOAEL

(WHO fibers/cc)

339 M 310 M 310 M 

LOAEL 

Less Serious 

(WHO fibers/cc) 

339 M (minimal-to-mild pulmonary 

inflammation) 

310 M (minimal-to-mild pulmonary 

inflammation) 

Serious 

(WHO fibers/cc) 

310 M (minimal to mild pulmonary and 

pleural fibrosis, pulmonary inflammation) 
27

310

310

5

1122

58

1022

59

215

Table 3-1 Levels of Significant Exposure to Synthetic Vitreous Fibers - Inhalation (continued) 

a

Key to Species 

figure (Strain) 

56 Hamster 

(Golden Syrian) 

57 Baboon 

Cancer 

58 Rat 

(Wistar) 

59 Hamster 

(Golden Syrian) 

Exposure/ 

Duration/ 

Frequency 

(Specific Route) System 

NOAEL 

(WHO fibers/cc) 

Less Serious 

(WHO fibers/cc) 

LOAEL 

Serious 

(WHO fibers/cc) 

6 mo 6 hr/d 5 d/wk (nose only) 

Resp 310 M (mild pulmonary and pleural 

fibrosis, pulmonary inflammation) 

Bd Wt 310 M 

8 mo 7 hr/d 5 d/wk (nose only) 

Resp 1122 M (pulmonary inflammation, scant 

ferruginous bodies) 

b 

1 yr 7 hr/d 5 d/wk 

1022 M (CEL: pleural mesotheliomas, 

lung adenomas and carcinomas) 

40 wk 5 d/wk 6 h/d (nose only) 

215 M (CEL: pleural mesotheliomas) 
64

29

232

65

29

232

67

41

246

68

41

246

Table 3-1 Levels of Significant Exposure to Synthetic Vitreous Fibers - Inhalation (continued) 

Exposure/ 

Duration/

a 

System 

Resp Bd Wt Resp Bd Wt Resp Bd Wt Resp Bd Wt 

LOAEL 

Species Frequency (Specific Route) (Strain) 

CHRONIC EXPOSURE

NOAEL

(WHO fibers/cc)

232 M 232 M 246 M 246 M 

Less Serious 

(WHO fibers/cc) 

29 M (minimal-to-mild pulmonary 

inflammation) 

29 M (minimal-to-mild pulmonary 

inflammation) 

41 M (minimal-to-mild pulmonary 

inflammation) 

41 M (minimal-to-mild pulmonary 

inflammation) 

Serious 

(WHO fibers/cc) 

Key to 

figure 

60 

Systemic 

(Fischer- 344) Rat 

61 

(Fischer- 344) Rat 

62 

(Fischer- 344) Rat 

63 

(Fischer- 344) Rat 

18 mo 6 hr/d 5 d/wk (nose only) 2 yr 6 hr/d 5 d/wk (nose only) 18 mo 6 hr/d 5 d/wk (nose only) 2 yr 6 hr/d 5 d/wk (nose only) 
92

180

180180180

93

180

180180180

Table 3-1 Levels of Significant Exposure to Synthetic Vitreous Fibers - Inhalation (continued) 

Exposure/ LOAEL 

a

Key to 

figure 

Duration/ 

Frequency 

(Specific Route) Species (Strain) NOAEL System (WHO fibers/cc) 

64 18 mo 

6 hr/d 5 d/wk (nose only) 

(Fischer- 344) Rat 

Resp Hepatic 180 M Renal 180 M Bd Wt 180 M 

65 2 yr 

6 hr/d 5 d/wk (nose only) 

(Fischer- 344) Rat 

Resp Hepatic 180 M Renal 180 M Bd Wt 180 M 

Less Serious 

(WHO fibers/cc) 

Serious 

(WHO fibers/cc) 

180 M (pulmonary inflammation) 180 M (pulmonary inflammation) 
74

291

291

75

291

291

81

220

220220220220

Table 3-1 Levels of Significant Exposure to Synthetic Vitreous Fibers - Inhalation (continued) 

a

Key to Species 

figure (Strain) 

66 

(Fischer- 344) Rat 

67 

(Fischer- 344) Rat 

68 

(Fischer- 344) Rat 

Exposure/ 

Duration/ 

Frequency 

(Specific Route) 

18 mo 6 hr/d 5 d/wk (nose only) 24 mo 6 hr/d 5 d/wk (nose only) 15 mo 6 hr/d 5 d/wk (nose only) 

System 

Resp Bd Wt Resp Bd Wt Resp Cardio Hepatic Renal Bd Wt 

NOAEL

(WHO fibers/cc)

291 M 291 M 220 M 220 M 220 M 220 M 

LOAEL 

Less Serious 

(WHO fibers/cc) 

291 M (minimal-to-slight pulmonary 

inflammation) 

291 M (minimal-to-moderate

pulmonary inflammation)

Serious 

(WHO fibers/cc) 

220 M (mild interstitial fibrosis, 

minimal-to-mild pleural fibrosis, pulmonary inflammation) 
82

220

220220220220

83

220

220220220220

Table 3-1 Levels of Significant Exposure to Synthetic Vitreous Fibers - Inhalation (continued) 

a

Key to 

figure 

Species 

(Strain) 

Exposure/ 

Duration/ 

Frequency 

(Specific Route) System 

NOAEL 

(WHO fibers/cc) 

Less Serious 

(WHO fibers/cc) 

LOAEL 

Serious 

(WHO fibers/cc) 

69 18 mo 

6 hr/d 5 d/wk (nose only) 

(Fischer- 344) Rat 

Resp 220 M (mild interstitial fibrosis, minima

pleural fibrosis, pulmonary inflammation) 

Cardio Hepatic Renal Bd Wt 

220 M 220 M 220 M 220 M 

70 2 yr 

6 hr/d 5 d/wk (nose only) 

(Fischer- 344) Rat 

Resp 220 M (mild-to-moderate interstitial 

fibrosis, minimal-to-mild pleural fibrosis, pulmonary inflammation) 

Cardio Hepatic Renal Bd Wt 

220 M 220 M 220 M 220 M 
84

182

182182182182

85

182

182182182182

Table 3-1 Levels of Significant Exposure to Synthetic Vitreous Fibers - Inhalation (continued) 

Exposure/ 

Duration/

a

Key to Species Frequency 

figure (Strain) (Specific Route) 

71 Rat 15 mo 

6 hr/d (Fischer- 344) 5 d/wk (nose only) 

72 Rat 18 mo 

6 hr/d (Fischer- 344) 5 d/wk (nose only) 

System 

Resp Cardio Hepatic Renal Bd Wt Resp Cardio Hepatic Renal Bd Wt 

LOAEL 

NOAEL Less Serious

(WHO fibers/cc) (WHO fibers/cc) 

Serious 

(WHO fibers/cc) 

182 M (mild interstitial fibrosis, 

minimal-to-mild pleural fibrosis, pulmonary inflammation) 

182 M 182 M 182 M 182 M 

182 M (mild interstitial fibrosis, 

minimal-to-mild pleural fibrosis, pulmonary inflammation) 

182 M 182 M 182 M 182 M 
86

182

182182182182

87

153

153153153153

Table 3-1 Levels of Significant Exposure to Synthetic Vitreous Fibers - Inhalation (continued) 

a

Key to 

figure 

Species 

(Strain) 

Exposure/ 

Duration/ 

Frequency 

(Specific Route) System 

NOAEL 

(WHO fibers/cc) 

Less Serious 

(WHO fibers/cc) 

LOAEL 

Serious 

(WHO fibers/cc) 

73 2 yr 

6 hr/d 5 d/wk (nose only) 

(Fischer- 344) Rat 

Resp 182 M (mild-to-moderate interstitial 

fibrosis, minimal pleural fibrosispulmonary inflammation) 

Cardio 182 M Hepatic Renal 

182 M 182 M 

Bd Wt 182 M 

74 15 mo 

6 hr/d 5 d/wk (nose only) 

(Fischer- 344) Rat 

Resp 153 M (minimal-to-mild interstitial 

fibrosis, pulmonary inflammation) 

Cardio 153 M Hepatic Renal 

153 M 153 M 

Bd Wt 153 M 
88

153

153153153153

89

153

153153153153

Table 3-1 Levels of Significant Exposure to Synthetic Vitreous Fibers - Inhalation (continued) 

a

Key to 

figure 

Species 

(Strain) 

Exposure/ 

Duration/ 

Frequency 

(Specific Route) System 

NOAEL 

(WHO fibers/cc) 

Less Serious 

(WHO fibers/cc) 

LOAEL 

Serious 

(WHO fibers/cc) 

75 18 mo 

6 hr/d 5 d/wk (nose only) 

(Fischer- 344) Rat 

Resp 153 M (minimal-to-mild interstitial 

fibrosis, minimal pleural fibrosispulmonary inflammation) 

Cardio 153 M Hepatic Renal 

153 M 153 M 

Bd Wt 153 M 

76 2 yr 

6 hr/d 5 d/wk (nose only) 

(Fischer- 344) Rat 

Resp 153 M (minimal-to-mild interstitial 

fibrosis, pulmonary inflammation) 

Cardio 153 M Hepatic Renal 

153 M 153 M 

Bd Wt 153 M 
79

26 75

187187187187

80

26

75

187187187187

Table 3-1 Levels of Significant Exposure to Synthetic Vitreous Fibers - Inhalation (continued) 

a

Key to 

figure 

Species 

(Strain) 

Exposure/ 

Duration/ 

Frequency 

(Specific Route) System 

NOAEL 

(WHO fibers/cc) 

Less Serious 

(WHO fibers/cc) 

LOAEL 

Serious 

(WHO fibers/cc) 

77 18 mo 

6 hr/d 5 d/wk (nose only) 

(Fischer- 344) Rat 

Resp 26 M (minimal-to-mild pulmonary 

inflammation) 

75 M (minimal-to-mild interstitial 

fibrosis) 

Cardio 187 M Hepatic Renal 

187 M 187 M 

Bd Wt 187 M 

78 2 yr 

6 hr/d 5 d/wk (nose only) 

(Fischer- 344) Rat 

Resp 26 M (minimal-to-mild pulmonary 

inflammation) 

c

75 M (minimal-to-mild interstitial 

fibrosis, pulmonary inflammation) 

Cardio 187 M Hepatic Renal 

187 M 187 M 

Bd Wt 187 M 
69

34

150

243243243243

70

34

150

243243243243

Table 3-1 Levels of Significant Exposure to Synthetic Vitreous Fibers - Inhalation (continued) 

Exposure/ 

Duration/

a

Key to Species Frequency 

figure (Strain) (Specific Route) 

79 Rat 18 mo 

6 hr/d (Fischer- 344) 5 d/wk (nose only) 

80 Rat 2 yr 

6 hr/d (Fischer- 344) 5 d/wk (nose only) 

System 

Resp Cardio Hepatic Renal Bd Wt Resp Cardio Hepatic Renal Bd Wt 

LOAEL 

NOAEL 

(WHO fibers/cc) 

Less Serious 

(WHO fibers/cc) 

Serious 

(WHO fibers/cc) 

34 M (pulmonary inflammation) 150 M (mild pulmonary fibrosis, 

pulmonary inflammation) 

243 M 243 M 243 M 243 M 

34 M (pulmonary inflammation) 150 M (mild pulmonary fibrosis, 

pulmonary inflammation) 

243 M 243 M 243 M 243 M 
71

30

213213213213

72

30

213213213213

Table 3-1 Levels of Significant Exposure to Synthetic Vitreous Fibers - Inhalation (continued) 

Exposure/ 

Duration/

a

Key to Species Frequency 

figure (Strain) (Specific Route) 

81 Rat 18 mo 

6 hr/d (Fischer- 344) 5 d/wk (nose only) 

82 Rat 24 mo 

6 hr/d (Fischer- 344) 5 d/wk (nose only) 

System 

Resp Cardio Hepatic Renal Bd Wt Resp Cardio Hepatic Renal Bd Wt 

LOAEL 

NOAEL 

(WHO fibers/cc) 

Less Serious 

(WHO fibers/cc) 

Serious 

(WHO fibers/cc) 

30 M (pulmonary inflammation) 

213 M 213 M 213 M 213 M 

30 M (pulmonary inflammation) 

213 M 213 M 213 M 213 M 
78

215

215215215215

66

339

339

Table 3-1 Levels of Significant Exposure to Synthetic Vitreous Fibers - Inhalation (continued) 

LOAEL 

a

Key to Species 

figure (Strain) 

83 Hamster 

(Golden Syrian) 

84 Hamster 

(Golden Syrian) 

Exposure/ 

Duration/ 

Frequency 

(Specific Route) 

18 mo 5 d/wk 6 hr/d (nose only) 18 mo 6 hr/d 5 d/wk (nose only) 

NOAEL Less Serious 

System (WHO fibers/cc) (WHO fibers/cc) 

Resp Cardio 215 M Hepatic 215 M Renal 215 M Bd Wt 215 M Resp 339 M (minimal-to-mild pulmonary 

inflammation) 

Bd Wt 339 M 

Serious 

(WHO fibers/cc) 

215 M (mild-to-moderate interstitial

fibrosis, moderate-to-marked pleural fibrosis, pulmonaryinflammation, mesothelialhyperplaisa)
73

310

310

60

1122

61

1122

100

182

101

153

Table 3-1 Levels of Significant Exposure to Synthetic Vitreous Fibers - Inhalation (continued) 

a

Key to Species 

figure (Strain) 

85 Hamster 

(Golden Syrian) 

86 Baboon 87 Baboon 

Cancer 

88 Rat 

(Fischer- 344) 

89 Rat 

(Fischer- 344) 

Exposure/ 

Duration/ 

Frequency 

(Specific Route) System 

NOAEL 

(WHO fibers/cc) 

Less Serious 

(WHO fibers/cc) 

LOAEL 

Serious 

(WHO fibers/cc) 

18 mo 6 hr/d 5 d/wk (nose only) 

Resp 310 M (mild pleural and interstitial 

fibrosis; mesothelial hyperplasia) 

Bd Wt 310 M 

18 mo 7 hr/d 5 d/wk (nose only) 

Resp 1122 M (focal peribronchiolar fibrosis; 

numerous pulmonary ferruginous bodies) 

b

30 mo 7 hr/d 5 d/wk (nose only) 

Resp 1122 M (focal peribronchiolar fibrosis; 

numerous pulmonary ferruginous bodies) 

b

2 yr 6 hr/d 5 d/wk (nose only) 

182 M (CEL: pulmonary adenomas 

and carcinomas, pleural mesotheliomas) 

2 yr 6 hr/d 5 d/wk (nose only) 

153 M (CEL: pleural mesothelioma) 
99

220

97

187

98

75

96

215

94

310

Table 3-1 Levels of Significant Exposure to Synthetic Vitreous Fibers - Inhalation (continued) 

a

Key to Species 

figure (Strain) 

90 Rat 

(Fischer- 344) 

91 Rat 

(Fischer- 344) 

92 Rat 

(Fischer- 344) 

93 Hamster 

(Golden Syrian) 

94 Hamster 

(Golden Syrian) 

Exposure/ 

Duration/ 

Frequency 

(Specific Route) System 

NOAEL 

(WHO fibers/cc) 

Less Serious 

(WHO fibers/cc) 

LOAEL 

Serious 

(WHO fibers/cc) 

2 yr 6 hr/d 5 d/wk (nose only) 

220 M (CEL: pulmonary carcinomas, 

pleural mesotheliomas) 

2 yr 6 hr/d 5 d/wk (nose only) 

187 M (CEL: pulmonary adenomas 

and carcinomas) 

2 yr 6 hr/d 5 d/wk (nose only) 

75 M (CEL: pleural mesothelioma) 

18 mo 5 d/wk 6 hr/d (nose only) 

215 M (CEL: pleural mesotheliomas) 

78 wk 6 hr/d 5 d/wk (nose only) 

310 M (CEL: pleural mesothelioma) 
95

200

Table 3-1 Levels of Significant Exposure to Synthetic Vitreous Fibers - Inhalation (continued) 

a

Key to 

figure 

Species 

(Strain) 

Exposure/ 

Duration/ 

Frequency 

(Specific Route) 

NOAEL Less Serious

System (WHO fibers/cc) (WHO fibers/cc) 

LOAEL 

Serious 

(WHO fibers/cc) 

95 

(Golden Syrian) Hamster 24 mo 

6 hr/d 5 d/wk (nose only) 

200 (CEL: pleural mesothelioma) 

a The number corresponds to entries in Figure 3-1.Doses are reported as WHO fibers/cc; (WHO fibers = particles with length >5μm, diameter <3 μm, and a length:width ratio =3:1)b Dose reported as NIOSH fibers/cc; (NIOSH fibers = particles with length >5μm and a length:width ratio =3:1)c Used to derive a chronic inhalation minimal risk level (MRL) of 0.03 WHO fibers/cc for refractory ceramic fibers, as described in detail in Appendix A. The Mbenchmark dose modeling approach and a cross-species dosimetric scaling factor derived from lung deposition and clearance models for RCF1 fibers in rats aContinuous-variable models in the EPA Benchmark Dose Software were fit to data for macrophage aggregation, bronchiolization, collagen deposition at the brand lung weight in F344 male rats exposed to RCF1 for 2 years. The best-fitting model for each endpoint was used to calculate benchmark concentrations anconfidence limits (BMCs and BMCLs in units of total fibers/cc) associated with 10% increase in lung weight, compared with controls, or a mean minimal score for the lesions. The point of departure for the MRL was selected as the BMCL associated with the most sensitive endpoint, the BMCL for macrophage aggregThe selected rat BMCL was converted to a human equivalent concentration (BMCLHEC =1 WHO fibers/cc) using a cross-species scaling factor of 0.07. The Bmacrophage aggregation was divided by an uncertainty factor of 30 (3 for interspecies extrapolation with dosimetric adjustment and 10 for human variability).Bd Wt = body weight; Cardio = cardiovascular; CEL = cancer effect level; d = day(s); Endocr = endocrine; (F) = feed; F = Female; G = gavage; Gastro = gastrogestational day; Gn pig = guinea pig; hemato = hematological; hr = hour(s); LOAEL = lowest-observed-adverse-effect level; M = male; min = minute(s); MMVF fiber; mo = month(s); Musc/skel = musculoskeletal; NOAEL = no-observed-adverse-effect level; occup = occupational; NS = not specified; RCF = refractory cerespiratory; (W) = drinking water; wk = week(s); yr = year(s)
Respiratory 

Figure 3-1. Levels of Significant Exposure to Synthetic Vitreous Fibers- Inhalatio

Acute (≤14 days) 

Systemic 

WHO fibers/cc 

10000 

2r 

3s* 1r* 

* NIOSH fibers/cc 1000 

c-Cat -Humans f-Ferret n-Mink Cancer Effect Level-Animals Cancer Effect Level-Humans 

d-Dog k-Monkey j-Pigeon o-Other LOAEL, More Serious-Animals LOAEL, More Serious-Humans 

r-Rat m-Mouse e-Gerbil LOAEL, Less Serious-Animals LOAEL, Less Serious-Humans 

p-Pig h-Rabbit s-Hamster NOAEL - Animals NOAEL - Humans 

q-Cow a-Sheep g-Guinea Pig 
Respiratory 

Figure 3-1. Levels of Significant Exposure to Synthetic Vitreous Fibers- Inhalation (Con

Intermediate (15-364 days) 

Systemic 

WHO fibers/cc 

10000 

57c* 6r 1000 7r

4r 5r 

51s 52s 53s

45s 46s 47s 48s 54s 55s 56s 8r 9r 10r 

50s 

17r 18r 

100 

14r 15r 16r 

49s 

11r 12r 13r 

* NIOSH fibers/cc 10 

c-Cat -Humans f-Ferret n-Mink Cancer Effect Level-Animals Cancer Effect Level-Humans 

d-Dog k-Monkey j-Pigeon o-Other LOAEL, More Serious-Animals LOAEL, More Serious-Humans 

r-Rat m-Mouse e-Gerbil LOAEL, Less Serious-Animals LOAEL, Less Serious-Humans 

p-Pig h-Rabbit s-Hamster NOAEL - Animals NOAEL - Humans 

q-Cow a-Sheep g-Guinea Pig 
Respiratory Cardiovas

Figure 3-1. Levels of Significant Exposure to Synthetic Vitreous Fibers- Inhalation (Con

Intermediate (15-364 days)

Systemic 

WHO fibers/cc 

10000 

1000 

22r 

44r 

23r 24r 25r 26r 50s 23r 24r 

27r 28r 29r 30r 36r

31r 32r 33r 34r 

100 37r 

37r 38r 39r 40r 

41r 42r 43r 

35r 36r 

10 

c-Cat -Humans f-Ferret n-Mink Cancer Effect Level-Animals Cancer Effect Level-Humans 

d-Dog k-Monkey j-Pigeon o-Other LOAEL, More Serious-Animals LOAEL, More Serious-Humans 

r-Rat m-Mouse e-Gerbil LOAEL, Less Serious-Animals LOAEL, Less Serious-Humans 

p-Pig h-Rabbit s-Hamster NOAEL - Animals NOAEL - Humans 

q-Cow a-Sheep g-Guinea Pig 
Cardiovascular Hepatic 

Figure 3-1. Levels of Significant Exposure to Synthetic Vitreous Fibers- Inhalation (Conti

Intermediate (15-364 days)

Systemic 

WHO fibers/cc 

10000 

1000 

37r 38r 39r 40r 26r 41r 42r 43r 50s 23r 24r 

27r 28r 29r 30r 35r 36r 17r 18r 19r 

31r 32r 33r 34r 

100 

10 

c-Cat -Humans f-Ferret n-Mink Cancer Effect Level-Animals Cancer Effect Level-Humans 

d-Dog k-Monkey j-Pigeon o-Other LOAEL, More Serious-Animals LOAEL, More Serious-Humans 

r-Rat m-Mouse e-Gerbil LOAEL, Less Serious-Animals LOAEL, Less Serious-Humans 

p-Pig h-Rabbit s-Hamster NOAEL - Animals NOAEL - Humans 

q-Cow a-Sheep g-Guinea Pig 
Hepatic Renal 

Figure 3-1. Levels of Significant Exposure to Synthetic Vitreous Fibers- Inhalation (Cont

Intermediate (15-364 days)

Systemic 

WHO fibers/cc 

10000 

1000 

38r 39r 40r 

41r 37r 23r 24r 25r 

29r 

42r 43r 50s

30r 35r 36r 

31r 

17r 18r 19r 

32r 33r 34r 

100 

10 

c-Cat -Humans f-Ferret n-Mink Cancer Effect Level-Animals Cancer Effect Level-Humans 

d-Dog k-Monkey j-Pigeon o-Other LOAEL, More Serious-Animals LOAEL, More Serious-Humans 

r-Rat m-Mouse e-Gerbil LOAEL, Less Serious-Animals LOAEL, Less Serious-Humans 

p-Pig h-Rabbit s-Hamster NOAEL - Animals NOAEL - Humans 

q-Cow a-Sheep g-Guinea Pig 
Renal Body Weight 

Figure 3-1. Levels of Significant Exposure to Synthetic Vitreous Fibers- Inhalation (Conti

Intermediate (15-364 days)

Systemic 

WHO fibers/cc 

10000 

1000 

51s 52s 53s 54s 55s 56s 

38r 39r 40r 

37r 11r 12r 1

41r 42r 43r 50s

35r 36r 

32r 33r 34r 

100 

10 

c-Cat -Humans f-Ferret n-Mink Cancer Effect Level-Animals Cancer Effect Level-Humans 

d-Dog k-Monkey j-Pigeon o-Other LOAEL, More Serious-Animals LOAEL, More Serious-Humans 

r-Rat m-Mouse e-Gerbil LOAEL, Less Serious-Animals LOAEL, Less Serious-Humans 

p-Pig h-Rabbit s-Hamster NOAEL - Animals NOAEL - Humans 

q-Cow a-Sheep g-Guinea Pig 
Body Weight 

Figure 3-1. Levels of Significant Exposure to Synthetic Vitreous Fibers- Inhalation (Contin

Intermediate (15-364 days)

Systemic 

WHO fibers/cc 

10000 

1000 

20r 21r 22r 

37r 38r 39r 40r 23r 24r 25r 26r 41r 42

35r 36r 

31r 

18r 19r 27r 28r 29r 30r

32r 33r 34r 

100 

*Doses represent the lowest dose tested per study that produced a tumorigenic response and do not imply the existence of a threshold for the cancer end point. 10 

c-Cat -Humans f-Ferret n-Mink Cancer Effect Level-Animals Cancer Effect Level-Humans 

d-Dog k-Monkey j-Pigeon o-Other LOAEL, More Serious-Animals LOAEL, More Serious-Humans 

r-Rat m-Mouse e-Gerbil LOAEL, Less Serious-Animals LOAEL, Less Serious-Humans 

p-Pig h-Rabbit s-Hamster NOAEL - Animals NOAEL - Humans 

q-Cow a-Sheep g-Guinea Pig 
Respiratory 

Figure 3-1. Levels of Significant Exposure to Synthetic Vitreous Fibers- Inhalation (Continue

Chronic (≥365 days) 

Systemic 

WHO fibers/cc 

10000 

86c* 87c* 1000 

84s 85s 66r 67r 

83s 68r 69r 70r 64r 65r 71r 72r 73r 74r 75r 76r 79r 80r 

100 

77r 78r 

62r 63r 79r 

60r 61r 

77r 78r 

10 

1 

0.1 

* NIOSH fibers/cc 0.01 

c-Cat -Humans f-Ferret n-Mink Cancer Effect Level-Animals Cancer Effect Level-Humans 

d-Dog k-Monkey j-Pigeon o-Other LOAEL, More Serious-Animals LOAEL, More Serious-Humans 

r-Rat m-Mouse e-Gerbil LOAEL, Less Serious-Animals LOAEL, Less Serious-Humans 

p-Pig h-Rabbit s-Hamster NOAEL - Animals NOAEL - Humans 

q-Cow a-Sheep g-Guinea Pig 
Cardiovascular 

Figure 3-1. Levels of Significant Exposure to Synthetic Vitreous Fibers- Inhalation (Contin

Chronic (≥365 days) 

Systemic 

WHO fibers/cc 

10000 

1000 

79r 80r 83s 68r 69r 70r 81r 82r 71r 72r 73r 77r 78r 74r 75r 76r

100 

10 

1 

0.1 

0.01 

c-Cat -Humans f-Ferret n-Mink Cancer Effect Level-Animals Cancer Effect Level-Humans 

d-Dog k-Monkey j-Pigeon o-Other LOAEL, More Serious-Animals LOAEL, More Serious-Humans 

r-Rat m-Mouse e-Gerbil LOAEL, Less Serious-Animals LOAEL, Less Serious-Humans 

p-Pig h-Rabbit s-Hamster NOAEL - Animals NOAEL - Humans 

q-Cow a-Sheep g-Guinea Pig 
Hepatic 

Figure 3-1. Levels of Significant Exposure to Synthetic Vitreous Fibers- Inhalation (Contin

Chronic (≥365 days)

Systemic 

WHO fibers/cc 

10000 

1000 

68r 69r 70r 79r 80r 83s 81r 82r 64r 65r 71r 72r 73r 77r 78r 74r 75r 76r

100 

10 

1 

0.1 

0.01 

c-Cat -Humans f-Ferret n-Mink Cancer Effect Level-Animals Cancer Effect Level-Humans 

d-Dog k-Monkey j-Pigeon o-Other LOAEL, More Serious-Animals LOAEL, More Serious-Humans 

r-Rat m-Mouse e-Gerbil LOAEL, Less Serious-Animals LOAEL, Less Serious-Humans 

p-Pig h-Rabbit s-Hamster NOAEL - Animals NOAEL - Humans 

q-Cow a-Sheep g-Guinea Pig 
Renal 

Figure 3-1. Levels of Significant Exposure to Synthetic Vitreous Fibers- Inhalation (Contin

Chronic (≥365 days) 

Systemic 

WHO fibers/cc 

10000 

1000 

79r 80r 83s 68r 69r 70r 81r 82r 64r 65r 71r 72r 73r 77r 78r 74r 75r 76r

100 

10 

1 

0.1 

0.01 

c-Cat -Humans f-Ferret n-Mink Cancer Effect Level-Animals Cancer Effect Level-Humans 

d-Dog k-Monkey j-Pigeon o-Other LOAEL, More Serious-Animals LOAEL, More Serious-Humans 

r-Rat m-Mouse e-Gerbil LOAEL, Less Serious-Animals LOAEL, Less Serious-Humans 

p-Pig h-Rabbit s-Hamster NOAEL - Animals NOAEL - Humans 

q-Cow a-Sheep g-Guinea Pig 
Body Weight 

Figure 3-1. Levels of Significant Exposure to Synthetic Vitreous Fibers- Inhalation (Contin

Chronic (≥365 days) 

Systemic 

WHO fibers/cc 

10000 

81r 82r 

1000 

84s 85s 66r 67r 94s 60r 61r 62r 63r 79r 80r 83s 68r 69r 70r 93s 

64r 65r 71r 72r 73r 77r 78r 95s 

74r 75r 76r 

100

10 

1 

0.1 

*Doses represent the lowest dose tested per study that produced a tumorigenic response and do not imply the existence of a threshold for the cancer end point. 

0.01 

c-Cat -Humans f-Ferret n-Mink Cancer Effect Level-Animals Cancer Effect Level-Humans 

d-Dog k-Monkey j-Pigeon o-Other LOAEL, More Serious-Animals LOAEL, More Serious-Humans 

r-Rat m-Mouse e-Gerbil LOAEL, Less Serious-Animals LOAEL, Less Serious-Humans 

p-Pig h-Rabbit s-Hamster NOAEL - Animals NOAEL - Humans 

q-Cow a-Sheep g-Guinea Pig 
SYNTHETIC VITREOUS FIBERS 79 

3. HEALTH EFFECTS 

>5 μm, diameter <3 μm, and aspect ratio ≥3:1). To facilitate comparison of effects across studies, this 

exposure unit is cited in Table 3-1 and Figure 3-1, except for a few studies (Everitt et al. 1994; Goldstein 

et al. 1983) in which fiber counting measurements were reported only in units using the NIOSH fiber 

counting rules (i.e., length >5 μm; aspect ratio ≥3:1). 

Respiratory Effects. 

Human Studies. 

Refractory Ceramic Fibers. Research into the health effects of refractory ceramic fibers has been limited 

by the relatively short time since manufacture began (50 years), small numbers of exposed workers, and 

confounding exposures (e.g., smoking and asbestos). 

Information regarding the effects of acute inhalation exposure to refractory ceramic fibers in humans is 

limited to a case-report that provided suggestive evidence of respiratory symptoms (cough, eye and throat 

irritation, wheezing, shortness of breath, and bronchospasm) that required medical treatment following 

1 hour of exposure to high levels (“like a snow storm”) of refractory ceramic fibers without respiratory 

protection (Forrester 1997). 

No human inhalation studies of intermediate duration (2 weeks–1 year) were located for refractory 

ceramic fibers. 

A low prevalence of pleural plaques (about 3%) has been the most biologically significant effect found in 

retrospective and longitudinal evaluations of the health of workers involved in the manufacture of 

refractory ceramic fibers in the United States (LeMasters et al. 1994; Lentz et al. 2003; Lockey et al. 

1996, 2002) and Europe (Cowie et al. 2001). However, consistent statistically significant associations 

with exposure to refractory ceramic fibers were only found in the U.S. cohort (Lentz et al. 2003; Lockey 

et al. 1996, 2002). Although diffuse pleural thickening and circumscribed pleural plaques have been 

associated with impairment of respiratory functions, localized pleural plaques are not thought to be a 

significant health hazard and have not been mechanistically linked to increased risks of lung fibrosis, lung 

cancer, or mesothelioma (Agency for Toxic Substances and Disease Registry 2001). Symptoms of dry 

cough, runny nose, wheezing, and breathlessness also have been reported in European manufacturing 

workers exposed to refractory ceramic fibers and other dusts (Burge et al. 1995; Trethowan et al. 1995). 
SYNTHETIC VITREOUS FIBERS 80 

3. HEALTH EFFECTS 

Additionally, some studies have observed decreased pulmonary function, usually in exposed workers with 

histories of smoking (Cowie et al. 2001; LeMasters et al. 1998; Lockey et al. 1998; Trethowan et al. 

1995). No fibrosis or other serious health effects have been demonstrated. Although participation rates 

are high, these studies have been limited by small cohort sizes and relatively short exposure durations. In 

the only cohort mortality study of refractory ceramic fiber manufacturing workers, there were no 

statistically significant excesses of death associated with any nonmalignant disease, including 

nonmalignant respiratory disease (LeMasters et al. 2003). 

A U.S. study of 627 current and 220 former refractory ceramic fiber production workers identified pleural 

changes in 23 men (LeMasters et al. 1994). The pleural changes were classified as plaques for 21 of the 

cases and thickening for the other 2 cases. Even after adjusting for potential asbestos exposure, a 

significant association remained between time since first employment and pleural plaques. 

A retrospective cohort study of radiographically detected chest changes in 652 workers from five U.S. 

refractory ceramic fiber plants initially detected 20 cases of pleural plaques (Lockey et al. 1996). In a 

later report of the survey of radiographic chest changes in U.S. refractory ceramic fiber workers 

(625 current workers at five plants and 383 former workers at two of the five plants), pleural changes 

were detected in 27 workers (2.7%) (Lockey et al. 2002). Twenty-two of the cases showed pleural 

plaques (86% of which were bilateral). In logistic regression analyses that adjusted for asbestos exposure 

and age, three exposure metrics (duration, time since first employment, and cumulative exposure) showed 

statistically significant trends for increasing odds ratios with increasing exposure. For example, 

respective odds ratios (ORs) for pleural changes were OR=2.2 (95% confidence interval (CI) 0.5–11.8), 

OR=5.6 (95% CI 1.5–28.1), and OR=6.0 (95% CI 1.4–31.0) for the following categories of increasing 

cumulative exposure (measured in units of fibers-month/cm3

): >15–45, >45–135, and >135. In a similar 

logistic regression analysis of data collected from the same cohort, odds ratios for pleural plaques showed 

statistically significant trends with increasing exposure categories for three different cumulative exposure 

metrics: cumulative exposure; cumulative pulmonary dose of all fibers; and cumulative pulmonary dose 

of fibers with diameters <0.4 μm and length <10 μm (Lentz et al. 2003). Pulmonary doses for each 

worker were estimated using air monitoring data from the plants, job histories, and a lung deposition 

model. 

A prospective study of 361 current male U.S. refractory ceramic fiber production workers found a 

statistically significant (but not biologically significant) decrease in forced vital capacity (FVC) among 
SYNTHETIC VITREOUS FIBERS 81 

3. HEALTH EFFECTS 

workers employed for >7 years at initial testing in 1987 compared to unexposed workers (OR not 

reported) (Lockey et al. 1998). However, these effects did not remain statistically significant in 

longitudinal analyses conducted until 1994. 

In an initial report of a cohort mortality study of male workers employed at two U.S. refractory ceramic 

fiber manufacturing plants between 1952 and 2000, no statistically significant excesses were found for 

deaths by any cause or deaths associated with nonmalignant diseases (LeMasters et al. 2003). A total of 

87 deaths were recorded among the 942 men included in the study (9% of the cohort). Eight deaths 

associated with nonmalignant respiratory disease were recorded, compared with an expected 7.49 deaths 

based on U.S. mortality rates (standardized mortality ratios [SMR]=107; 95% CI 46–211). 

A cross-sectional study of workers from seven European refractory ceramic fiber manufacturing plants 

showed an association between nasal, skin, and eye symptoms and worker exposure (Burge et al. 1995; 

Rossiter et al. 1994; Trethowan et al. 1995). A total of 628 employees participated in the study (91% 

were men). Workplace air monitoring data were available for inspirable dust mass and respirable fibers. 

In a multiple logistic regression analysis of exposure to inspirable dust and respirable fibers, significantly 

increased odds ratios for dry cough, dyspnea (grade 2), stuffy nose, eye irritation, and skin irritation were 

noted for the highest exposure group compared with the lowest exposure group (Burge et al. 1995). No 

relationships were noted for wheeze or chronic bronchitis with increasing exposure (Burge et al. 1995). 

When the effects of exposure to inspirable dust mass or respirable fibers were examined as independent 

variables, the odds ratio was significantly increased only for skin irritation for respirable fibers and for 

wheeze, dyspnea, and eye irritation for inspirable mass (Burge et al. 1995). A multiple linear regression 

analysis (which adjusted for confounders such as age) showed that lung function variables in current 

smokers (forced expiratory volume in 1 second [FEV1] and forced midexpiratory flow, [FEF25-75]) 

decreased with increasing cumulative exposure to respirable fibers (Trethowan et al. 1995). Chest x-rays 

did not show any effects related to exposure to respirable fibers (Trethowan et al. 1995). 

In a subsequent cross-sectional morbidity study of 774 ceramic fiber production workers from six 

European refractory ceramic fiber manufacturing plants, the prevalence of radiographic pleural changes 

was more strongly related to age and any previous occupational exposure to asbestos than to exposure 

metrics for refractory ceramic fibers (Cowie et al. 2001). Pleural plaques or pleural changes were noted 

in 9 or 32 workers, respectively, among the 355 workers without some occupational exposure to asbestos 

(about 3 or 9%, respectively). In logistic regression analyses that adjusted for age, elevated odds ratios 
SYNTHETIC VITREOUS FIBERS 82 

3. HEALTH EFFECTS 

for pleural plaques or pleural changes were calculated for refractory ceramic workers without asbestos 

exposure and with >10 years since first exposure to refractory ceramic fibers: OR=2.03 (95% CI 0.78– 

5.25) for pleural plaques and OR=2.22 (95% CI 1.17–4.24) for pleural changes. Exposure-related 

changes in pulmonary function variables were restricted to the finding that FEV1 and FVC in workers 

who smoked showed decreasing values with increasing measures of exposure. 

Glass Wool, Rock and Slag Wool, and Continuous Filament Glass Fibers. In people, acute exposures 

to fibrous glass materials including continuous glass filament (e.g., fiberglass fabrics), glass wool 

insulation, and rock and slag wool have been associated with symptoms of upper respiratory tract 

irritation such as nasal itching and congestion, nosebleed, sore throat, cough, and laryngeal and 

pharyngeal pain (Horvath 1995; Milby and Wolf 1969; Nasr et al. 1971; Newball and Brahim 1976; 

Petersen and Sabroe 1991; Thriene et al. 1996). These symptoms have been reported to disappear shortly 

following cessation of exposure. Upper respiratory tract irritation has been associated mostly with 

unusually dusty workplace conditions (concentrations >1 fiber/cc) involving removal of fibrous glass 

materials in closed spaces without respiratory protection (ACGIH 2001; EPA 1980), and similar 

symptoms of upper respiratory irritation may also occur in workers involved in the manufacture, 

application, or removal of insulation materials made from rock wool or slag wool (ACGIH 2001). 

Reliable data regarding the effects of intermediate (2 weeks–1 year) inhalation exposure of people to 

continuous glass fibers, glass wool, and rock and slag wool are limited because cross-sectional studies 

have been limited to workers with longer exposures and cohort studies have frequently been confounded 

by strong healthy worker effects (Boffetta et al. 1997, 1998, 1999; Lea et al. 1999; Marsh et al. 2001a; 

Sali et al. 1999; Shannon et al. 1987, 1990). 

The possible effects of chronic exposure to continuous glass fibers, glass wool, and rock and slag wool 

have been investigated in cross-sectional health evaluation studies, cohort mortality studies, and casecontrol studies. Respiratory symptoms similar to those seen in acute studies (decreased pulmonary 

function, coughing, bronchitis) have been reported (Albin et al. 1998; Clausen et al. 1993; Engholm and 

von Schmalensee 1982; Kilburn et al. 1992). Attempts to determine whether or not exposure to 

continuous glass filament, glass wool, and rock and slag wool induced pleural plaques have been 

inconclusive or negative (Hughes et al. 1993; Kilburn and Warshaw 1991; Kilburn et al. 1992; Sanden 

and Jarvholm 1986; Scansetti et al. 1993; Weill et al. 1983). Cohort mortality studies have found no 
 

 

SYNTHETIC VITREOUS FIBERS 83 

3. HEALTH EFFECTS 

association between exposure and increased risk for mortality from nonmalignant respiratory disease 

(Hunting and Welch 1993; Marsh et al. 2001a; Sali et al. 1999; Shannon et al. 1987, 1990). 

Cross-sectional studies of populations working with fibrous glass have focused on the prevalence of 

respiratory symptoms through the administration of questionnaires, pulmonary function testing, and chest 

x-ray examinations (Clausen et al. 1993; Ernst et al. 1987; Gross 1976; Hansen et al. 1999; Hill et al. 

1973; Hughes et al. 1993; Kilburn et al. 1992; Moulin et al. 1988; Nasr et al. 1971; Sanden and Jarvholm, 

1986; Weill et al. 1983; Wright 1968). In general, these studies reported no consistent evidence for 

increased prevalences of adverse respiratory symptoms, abnormal pulmonary functions, or chest x-ray 

abnormalities (e.g., pneumonia, bronchitis, emphysema, pleural effusion and thickening, solid lesions, 

and abnormal heart and aorta). However, increased incidences of coughing (Albin et al. 1998) and 

bronchitis (Engholm and von Schmalensee 1982) among Swedish construction workers exposed to glass 

and rock wool as well as decreased pulmonary function (forced expiratory volume in 1 second) among 

Danish construction workers exposed to glass and rock wool (Clausen et al. 1993) and U.S. appliance 

assembly workers exposed to glass wool (Kilburn et al. 1992) have been observed. These studies did not 

have data regarding symptoms following cessation of exposure, so the persistence of these symptoms is 

unknown. In addition, information of exposure levels experienced by these workers was unavailable. 

Because occupational exposure to inhaled asbestos has been associated with changes in the pleural 

membrane (such as plaques, thickening, and fibrosis) (Agency for Toxic Substances and Disease Registry 

2001), several cross-sectional studies analyzed chest x-rays of workers exposed to synthetic vitreous 

fibers but did not find consistent evidence for an association between pleural changes and exposure to 

fibrous glass, rockwool, or slag wool. No increased incidence of pleural plaques or radiographic densities 

were seen in a study of 1,401 continuous glass filament and glass wool production workers (Wright 1968) 

or in a study of 788 male and 145 female rock wool production workers (Jarvholm et al. 1995). An initial 

cross-sectional study performed in 1979–1980 of U.S. fiberglass and mineral wool workers detected a low 

prevalence of small lung opacities of low profusion that correlated significantly with duration of 

employment at two of the seven plants studied (Weill et al. 1983). However, in a follow-up study that 

used prevalences of opacities in a local population as a control, no excesses of opacities were identified in 

the exposed workers that were related to fiber exposure (Hughes et al. 1993). Two other studies observed 

opacities in groups of workers, but did not report data for reference populations, so the results are 

inconclusive (Kilburn and Warshaw 1992; Kilburn et al. 1992). Lung radiographic abnormalities were 

seen in 8 of 38 glass wool production workers exposed to fiberglass but not to asbestos and in 23 of 
SYNTHETIC VITREOUS FIBERS 84 

3. HEALTH EFFECTS 

137 workers exposed to both asbestos and fiberglass (Kilburn and Warshaw 1992). A separate study of 

appliance assembly workers exposed to glass wool observed radiographic abnormalities in 43 of 

284 workers (Kilburn et al. 1992). Although 36 of these cases were attributed to fiberglass exposure, the 

adjustments made for self-reported asbestos exposure and smoking data were unclear (Bender 1993). 

Other studies observed pleural plaques and cough with phlegm only among fibrous glass workers with 

reported or suspected co-exposure to asbestos (Sanden and Jarvholm 1986; Scansetti et al. 1993). 

Data for mortality from nonmalignant respiratory diseases were analyzed for three major groups of 

workers involved in the manufacture of workers exposed to filament glass fibers, glass wool, rock wool, 

or slag wool in the United States (Bayliss et al. 1976; Chiazze et al. 1997, 2002; Enterline and Henderson 

1975; Enterline et al. 1983; Marsh et al. 1990, 2001a; Robinson et al. 1982; Wong et al. 1991; Watkins et 

al. 1997), Europe (Claude and Frentzel-Beyme 1984, 1986; Gustavsson et al. 1992; Lea et al. 1999; Sali 

et al. 1999; Simonato et al. 1986a; Teppo and Kojonen 1986), and Canada (Shannon et al. 1984, 1987, 

1990). These cohort studies (and their associated case-control studies) have the strengths of large sample 

sizes, long follow-up periods, low losses in follow-up, and use of existing employment records to assess 

exposure, but have the limitations of imprecise estimations of actual exposure levels and the inability to 

adjust for confounding from tobacco smoke and concomitant exposure to other hazardous agents in the 

workplace. (These cohort studies are also discussed in Section 3.2.1.7, Cancer.) 

The available cohort studies observed no increased risk of mortality from nonmalignant respiratory 

diseases in U.S., European, or Canadian workers. Significantly decreased risks of mortality from 

nonmalignant respiratory disease compared with national rates reported in the U.S. fiberglass cohort 

(Marsh et al. 2001a) and in the Canadian studies on glass wool (Shannon et al. 1984, 1987) and glass 

filament (Shannon et al. 1990) workers are consistent with a possible healthy worker effect, but the 

European cohort study did not find decreased risks (Sali et al. 1999). Categories of nonmalignant 

respiratory disease considered by these major studies were divided by organ (larynx, bronchus, trachea, 

and lung) and health effect (including asthma, bronchitis, emphysema, influenza, and pneumonia). 

Similarly, a cohort of 333 U.S. sheet metal workers investigating obstructive lung disease did not 

consider exposure to fiberglass as a risk factor (Hunting and Welch 1993). 
SYNTHETIC VITREOUS FIBERS 85 

3. HEALTH EFFECTS 

Animal Studies. 

Although many animal studies administering various synthetic vitreous fibers by injection or implantation 

into the intrapleural or intraperitoneal cavities have reported the development of administration site 

nonneoplastic and neoplastic lesions (see Section 2.2.4, Other Routes of Exposure), these results are of 

limited usefulness for predicting health hazards in humans exposed by inhalation. Studies that exposed 

animals by inhalation to well-measured levels of respirable fibers are considered more appropriate for 

assessing potential risk to human health. 

Studies in rats (Bellmann et al. 2001; Brown et al. 2000; Cullen et al. 2000; Everitt et al. 1997; 

Gelzleichter et al. 1996a, 1996b, 1996c, 1999; Haratake et al. 1995; Hesterberg et al. 1993c, 1998b, 1999; 

Johnson and Wagner 1980; Kamstrup et al. 1998, 2001; Le Bouffant et al. 1987; Lee et al. 1981b; Mast et 

al. 1995a, 1995b; McConnell et al. 1994, 1999; Muhle et al. 1987; Smith et al. 1987; Yokosakai et al. 

1991), hamsters (Everitt et al. 1997; Gelzleichter et al. 1996a, 1996b, 1996c, 1999; Hesterberg et al. 1999; 

Lee et al. 1981b; McConnell et al. 1995; Smith et al. 1987), guinea pigs (Lee et al. 1981b), and baboons 

(Goldstein et al. 1983) have observed consistent, dose-related responses to the inhalation of synthetic 

vitreous fibers; and only one study reported a NOAEL for respiratory effects (Muhle et al. 1987; see 

Figure 3-1). In the lungs, an immediate inflammatory response has been observed in rats and mice at the 

lowest exposure-levels tested, approximately 30–40 WHO fibers/cc of glass wool (Hesterberg et al. 

1993c, 1999), rock wool (McConnell et al. 1994), slag wool (McConnell et al. 1994), and refractory 

ceramic fibers (Mast et al. 1995a, 1995b). End points used to measure lung inflammation include 

infiltration of macrophages (which accumulate fibrous and nonfibrous inhaled particles), microgranuloma 

formation (nonneoplastic focal accumulations of macrophages), increases in other immune cells, and 

increases in biochemical markers (lactate dehydrogenase, gamma-glutamyl transferase, N-acetylglucoseaminidase, glutathione, fibronectin, and total protein). Although the intensity of inflammatory changes 

increased with increasing exposure, these effects have subsided rapidly after cessation of exposure and 

are therefore not considered serious in the absence of other lesions. The reversible pulmonary 

inflammatory effects observed following repeated inhalation exposure to synthetic vitreous fibers are 

typical of the lung’s response to other relatively water-insoluble particles, both non-fibrous and fibrous 

particles (Churg et al. 2000; Driscoll 1996; Hesterberg and Hart 2001; Kane 1996; Mossman and Churg 

1998). In animal studies where exposure atmospheres included nonfibrous particles (e.g., the studies of 

the refractory ceramic fiber preparation, RCF1, reported by Mast et al. [1995a, 1995b]), the nonfibrous 
SYNTHETIC VITREOUS FIBERS 86 

3. HEALTH EFFECTS 

particles are expected to have contributed to the observed inflammatory responses to some undetermined 

degree (Maxim et al. 2003b). 

With repeated exposure scenarios to higher concentrations, more serious effects have been seen. 

Epithelial hyperplasia and alveolar bronchiolization, an epithelial cell transition from flat to cuboidal 

morphology, have been seen following chronic exposure to concentrations as low as about 180– 

240 WHO fibers/cc for several types of synthetic vitreous fibers including insulation glass wools 

(MMVF10, MMVF11; Hesterberg et al. 1993c), refractory ceramic fibers (RCF1, RCF2, RCF 3, RCF4; 

Mast et al. 1995a, 1995b), and rock and slag wools (MMVF21, MMVF22; McConnell et al. 1994). For 

some fibers (e.g., refractory ceramic fibers, MMVF21, MMVF33, C102/C104 blend fibrous glass), signs 

of minimal-to-moderate fibrosis following repeat exposure have been observed (Bellman et al. 2001; 

Goldstein et al. 1983; Mast et al. 1995a, 1995b; McConnell et al. 1994, 1995, 1999). Severe fibrosis was 

reported by only one study, with 104E-glass, a specialty continuous glass filament (Cullen et al. 2000). 

Because no regression has been observed following cessation of exposure, fibrosis is considered a serious 

respiratory lesion. 

Refractory Ceramic Fibers. The nonneoplastic respiratory effects of inhalation exposure to refractory 

ceramic fibers have been studied in conjunction with carcinogenicity studies (see Section 3.2.1.7, 

Cancer). In addition to intermediate and chronic studies in both rats and hamsters demonstrating 

reversible inflammation and irreversible fibrosis (Bellmann et al. 2001; Brown et al. 2000; Everitt et al. 

1994, 1997; Gelzleichter et al. 1996a, 1996b, 1996c, 1999; Hesterberg et al. 1998b; Mast et al. 1995a, 

1995b; McConnell et al. 1995; Smith et al. 1987; Yokosakai et al. 1991), acute- and intermediate-duration 

studies have found increased pleural mesothelial cell proliferation following acute and intermediate 

exposure in both hamsters and rats (Everitt et al. 1994, 1997; Gelzleichter et al. 1999). 

Although early rodent inhalation studies provided only limited information regarding the refractory 

ceramic fiber tested (Smith et al. 1987; Yokosakai et al. 1991), subsequent studies have identified specific 

types of refractory ceramic fibers: RCF1 is a kaolin-based refractory ceramic fiber (55–75% fiber), 

RCF1a is a fiber-enriched preparation of RCF1 containing 98% fiber, RCF2 is an aluminum zirconiabased fiber, RCF3 is a high-purity kaolin, and RCF4 is an “after-service” kaolin-based fiber previously 

exposed to high temperatures. Most studies have focused on RCF1, which is comparable to RCF3 (Mast 

et al. 1995a) and more toxic than RCF2 or RCF4 (Mast et al. 1995a). 
 

SYNTHETIC VITREOUS FIBERS 87 

3. HEALTH EFFECTS 

Acute studies are only available for RCF1, and have observed pulmonary and pleural inflammation 

(Everitt et al. 1994; Gelzleichter et al. 1996a, 1996b, 1996c). In both Fischer 344 rats and male Syrian 

Golden hamsters exposed nose-only to 1,700 NIOSH fibers/cc of RCF1 (6,900 total particles/cc) for 

5 days, end points demonstrating inflammation included increased relative numbers of pulmonary 

neutrophils (without changing total numbers of lavaged cells in the bronchoalveolar lavage fluid) and 

increased lung mesothelial cell proliferation; pleural neutrophil frequency was increased only in hamsters 

(Everitt et al. 1994). Similarly, male Fischer 344 rats exposed to 2,645 WHO fibers/cc of RCF1 (55% 

fiber; 89 mg/m3

) exhibited pulmonary and pleural inflammation following 5 days of exposure or at 

4 weeks postexposure (Gelzleichter et al. 1996a, 1996b). The pulmonary inflammation consisted of a 

dramatic and transient increase in bronchoalveolar levels of neutrophils, a delayed increase in pleural 

monocyte and eosinophil numbers, and a sustained (for 4 weeks) increase in bronchoalveolar markers for 

inflammation (lactate dehydrogenase, N-acetyl glucosaminidase, alkaline phosphatase, total protein, 

albumin, soluble fibronectin, and leukocyte fibronectin secretion). Pleural inflammation was more 

limited, and was measured with biochemical markers (increased N-acetyl glucosaminidase and leukocyte 

fibronectin secretion only immediately after exposure and increased total protein, albumin, and soluble 

fibronectin only at 4 weeks postexposure). 

Intermediate-duration nose-only inhalation experiments with refractory ceramic fibers in male Fischer 

344 rats (Mast et al. 1995a, 1995b), female Wistar rats (Bellmann et al. 2001; Brown et al. 2000), and 

male Syrian Golden hamsters (Everitt et al. 1997; Gelzleichter et al. 1999; McConnell et al. 1995) have 

verified the observations of pulmonary and pleural inflammation, and have also shown signs of 

progressive fibrosis. 

In male Fischer 344 rats, concentrations of RCF1 as low as 26 WHO fibers/cc (3 mg/m3

) for 3 months 

have caused pulmonary inflammation (statistically significant increases in relative lung weight, 

macrophage infiltration, and microgranuloma [nonneoplastic focal accumulation of macrophages] 

formation) (Mast et al. 1995a, 1995b). Exposure for the same duration to at least 75 WHO fibers/cc 

(9 mg/m3

) caused another sign of inflammation, alveolar bronchiolization. Alveolar bronchiolization is a 

pathologic response in which cells lining the alveoli become cuboidal (i.e., resembling cells lining the 

bronchioles). No fibrosis was seen in rats exposed to 26 WHO fibers/cc of RCF1; 75 WHO fibers/cc 

caused minimal-to-mild interstitial fibrosis by 12 months, and 187 WHO fibers/cc of RCF1 caused 

minimal-to-mild pleural fibrosis by 9 months (Mast et al. 1995a, 1995b). Following cessation of 

exposure, macrophage infiltration and bronchiolization rapidly regressed, but fibrosis neither progressed 
 

 

SYNTHETIC VITREOUS FIBERS 88 

3. HEALTH EFFECTS 

nor regressed. Other studies in male Fischer 344 rats with RCF1 have also reported pulmonary 

inflammation (statistically significant increases in pleural neutrophil, eosinophil and lymphocyte 

numbers, and biochemical markers of inflammation [pleural lactate dehydrogenase, N-acetylglucosaminidase, total protein, and fibronectin]) as well as pleural mesothelial cell proliferation following at 

least 4 weeks of exposure to 300 WHO fibers/cc (45.6 mg/m3

) (Everitt et al. 1997; Gelzleichter et al. 

1999). 

Exposure of male Fischer 344 rats to single exposure levels of RCF2, RCF3, or RCF4 (220, 182, or 

153 WHO fibers/cc, respectively, equivalent to 30 mg/m3

 for each) for at least 3 months caused 

pulmonary inflammation (macrophage infiltration and microgranuloma formation, bronchiolization of 

proximal alveoli) (Mast et al. 1995a). Minimal-to-mild focal pleural fibrosis was induced by RCF2 and 

RCF3 in as little as 6 months and by RCF4 within 9 months (Mast et al. 1995a). 

Pulmonary inflammation and slight interstitial fibrosis were also seen in female Wistar rats exposed to 

679 WHO fibers/cc of RCF1 (51.2 mg/m3

) or 481 WHO fibers/cc of RCF1a (25.8 mg/m3) for 3 weeks 

(Bellmann et al. 2001; Brown et al. 2000). RCF1a was a preparation of the same material cerused to 

prepare RCF1, but was prepared so that aerosols made from it contained less nonfibrous particles than 

RCF1 aerosols. Approximately 25% of the mass of RCF1 was accounted for by nonfibrous particles 

compared to about 2% in RCF1a. Inflammation consisted of statistically significantly increased relative 

and absolute lung weight, biochemical markers of bronchoalveolar inflammation (lactic dehydrogenase, 

gamma-glutamyl transferase, total protein, and glutathione), and bronchoalveolar infiltration by both 

macrophages and lymphocytes. Histopathological analyses observed slight interstitial fibrosis, bronchioalveolar hyperplasia, and alveolar histiocytosis. Bronchioalveolar inflammation and hyperplasia subsided 

within 3 months postexposure, but neither interstitial fibrosis nor alveolar histiocytosis decreased within 

the 1-year postexposure observation period. Exposure to RCF1 caused a severe retardation of alveolar 

clearance, but RCF1a did not, suggesting that the effect may have been a nonspecific response to total 

lung burden. 

Intermediate-duration studies with RCF1 in male Syrian Golden hamsters also demonstrated pulmonary 

inflammation and both interstitial and pleural fibrosis (Everitt et al. 1997; Gelzleichter et al. 1999; 

McConnell et al. 1995). In hamsters, concentrations as low as 215 WHO fibers/cc (30 mg/m3

) of RCF1 

induced a dramatic bronchioalveolar infiltration by macrophages accompanied by the appearance of 

microgranulomas, and progressive pulmonary and pleural fibrosis (including alveolar bronchiolization, 
SYNTHETIC VITREOUS FIBERS 89 

3. HEALTH EFFECTS 

punctate pleural foci, and collagen deposition) from 3 months onward (McConnell et al. 1995). In the 

recovery animals (treatment stopped at 3, 6, 9, or 12 months) examined at 18 months, no progression or 

regression of fibrosis was observed versus comparably-exposed interim sacrifices, although macrophage 

levels quickly reverted to normal. Male Syrian hamsters exposed to approximately 300 WHO fibers/cc of 

RCF1 (46 mg/m3

) for as short a duration as 4 weeks also exhibited statistically significant increases in 

pleural neutrophil, eosinophil, and lymphocyte numbers; biochemical markers of inflammation (pleural 

lactate dehydrogenase, N-acetylglucosaminidase, total protein, and fibronectin); pleural mesothelial cell 

proliferation; and visceral pleural collagen levels (Everitt et al. 1997; Gelzleichter et al. 1999). 

Chronic studies have observed similar respiratory effects in rats (Hesterberg et al. 1998b; Mast et al. 

1995a, 1995b) and hamsters (McConnell et al. 1995; Smith et al. 1987). Male Fischer 344 rats exposed to 

at least 26 WHO fibers/cc of RCF1 (3 mg/m3

) for 18 or 24 months showed increased lung weight, 

macrophage infiltration with microgranuloma formation, alveolar bronchiolization, and pleural and 

interstitial fibrosis (Mast et al. 1995b). Exposure of male Fischer 344 rats to RCF2, RCF3, or RCF4 (220, 

182, or 153 WHO fibers/cc, respectively, equivalent to 30 mg/m3

 for each) for 18 or 24 months caused 

pulmonary inflammation (macrophage infiltration and microgranuloma formation, bronchiolization of 

proximal alveoli) and minimal-to-moderate interstitial fibrosis and focal pleural fibrosis (Mast et al. 

1995a). Exposure to RCF1, RCF2, or RCF3 (but not RCF4) also caused bronchiolar-alveolar hyperplasia 

No nonmalignant respiratory effects were reported for male Syrian hamsters or female Osborne-Mendel 

rats exposed to 200 fibers/cc (12 mg/m3

) of an unspecified refractory ceramic fiber (diameter 1.8 μm) for 

2 years, but these results are inconclusive due to data reporting limitations (Smith et al. 1987; this 

NOAEL is not in Table 3-1 or Figure 3-1). Male Syrian Golden hamsters exposed for 15 or 18 months to 

215 WHO fibers/cc (30 mg/m3

) of RCF1 exhibited dramatic pulmonary inflammation (bronchioalveolar 

infiltration of macrophages, accompanied by the appearance of microgranulomas, alveolar 

bronchiolization), as well as mild-to-moderate interstitial and pleural fibrosis (McConnell et al. 1995). 

Glass Wool (Insulation Glass Wools and Special Purpose Glass Fibers). No acute-duration glass wool 

inhalation studies in animals were identified. 

All but one (Tempstran 475, Code 104 fiber, a special purpose glass fiber) of the glass wools induced 

pulmonary inflammation in animals following intermediate- or chronic-duration inhalation exposure 

(Muhle et al. 1987). However, the only glass wools to induce fibrosis were C102/C104 blend fibrous 
SYNTHETIC VITREOUS FIBERS 90 

3. HEALTH EFFECTS 

glass (with chronic- but not intermediate-duration exposure) (Goldstein et al. 1983), and two special 

purpose glass fibers (with intermediate- and chronic-duration exposures): MMVF33 (McConnell et al. 

1999) and 104E-glass (Cullen et al. 2000). 

The glass wools best characterized in animal inhalation studies are MMVF10, MMVF11, and MMVF33 

(Hesterberg et al. 1993c, 1999; McConnell et al. 1999). MMVF10 and MMVF11 are standard building 

insulation glass wools, whereas MMVF33 is a more durable special purpose glass fiber. Short-duration 

multiple-exposure-level studies with MMVF10 in male Syrian Golden hamsters observed minimal 

pulmonary inflammation (macrophage infiltration and microgranuloma formation) at levels as low as 

36 WHO fibers/cc after 13 weeks and 316 WHO fibers/cc after 7 weeks (3.2 and 30.5 mg/m3

, 

respectively) (Hesterberg et al. 1999). At 13 weeks, additional signs of inflammation were seen at the 

next-lowest concentration (increased numbers of pleural and pulmonary neutrophils and lymphocytes at 

concentrations as low as 206 WHO fibers/cc [16.5 mg/m3

]) (Hesterberg et al. 1999). These results are 

consistent with observations of pulmonary inflammation (macrophage infiltration and microgranuloma 

formation) in male Wistar rats exposed to the same approximate gravimetric concentration (2.2 mg/m3

; 

fiber/cc counts not reported) of GB100R glass wool (Haratake et al. 1995) and in male Fischer rats 

exposed to 29 and 41 WHO fibers/cc (3.1 and 4.8 mg/m3

) of either MMVF10 or MMVF11, respectively 

(Hesterberg et al. 1993c). No differences between MMVF10 and MMVF11 were observed in the latter 

experiment; no fibrosis was induced at the highest concentrations tested, 232 and 246 WHO fibers/cc 

(27.8 and 28.3 mg/m3

), and no progression of effects was seen in animals sacrificed at 18 or 24 months 

compared to those sacrificed at 12 months. 

The other rodent experiment, which included both intermediate and chronic timepoints, tested MMVF10a 

(a low fluorine preparation of MMVF10) and MMVF33 (a durable special applications glass fiber) for 

18 months in male Syrian Golden hamsters at concentrations of 339 or 310 WHO fibers/cc, respectively 

(29.6 or 37 mg/m3

) (McConnell et al. 1999). Pulmonary inflammation was seen as early as 13 weeks 

(macrophage infiltration and microgranuloma formation). MMVF10a did not induce fibrosis, but 

MMVF33 induced mild-to-moderate interstitial and pleural fibrosis as well as other markers of 

inflammation (increased absolute lung weight; neutrophil, eosinophil, and lymphocyte infiltration; 

elevated lactate dehydrogenase, beta-glucuronidase, and total protein levels; alveolar bronchiolization), 

beginning at 13 weeks. Both glass fibers induced mesothelial (but not bronchoalveolar) hyperplasia at 

18 months (not measured at previous timepoints). 
SYNTHETIC VITREOUS FIBERS 91 

3. HEALTH EFFECTS 

In male Wistar rats exposed whole-body at 1,022 WHO fibers/cc to 104E-glass or 1,019 WHO fibers/cc 

of 100/475 glass (two special-purpose glass fibers) for 1 year, both fiber types caused “considerable” 

pulmonary inflammation (macrophage infiltration associated with alveolar wall thickening), but only 

104E-glass produced considerable fibrosis (Cullen et al. 2000). Rats exposed for 1 year to 104E-glass 

and allowed to recover for an additional year exhibited bronchoalveolar hyperplasia and fibrosis more 

advanced than in animals sacrificed immediately after exposure. In nine rats exposed to 104E-glass that 

survived during the “recovery” period, advanced alveolar fibrosis and bronchoalveolar hyperplasia 

covered an average 8% of lung parenchyma area. In contrast, this lesion covered only 0.2 and 0.08% of 

lung parenchyma in 100/475-exposed rats and control rats, respectively. 

The other intermediate (Goldstein et al. 1983; Johnson and Wagner 1980; Lee et al. 1981b; Muhle et al. 

1987) and chronic (Goldstein et al. 1983; Le Bouffant et al. 1987; Smith et al. 1987) studies of other glass 

wools reported minimal respiratory effects (pulmonary inflammation), but no serious nonneoplastic health 

effects (such as fibrosis). 

The only experiment with glass wool performed in a nonrodent species used baboons (Papio ursinus) and 

was applicable to both intermediate and chronic exposure (Goldstein et al. 1983). A group of 10 male 

baboons were exposed to 1,122 fibers (with lengths >5 μm)/cc of a C102–C104 blend of fibrous glass 

(7.54 mg/m3

; 5.80 mg/m3 respirable) for 35 months with periodic lung biopsies. Pulmonary inflammation 

was seen at 8 months (pulmonary infiltration by histiocytes, fibroblasts, and giant cells, respiratory 

bronchiole wall thickening, and occurrences of ferruginous bodies). By 18 months, focal peribronchiolar 

fibrosis was detected. These results are inconclusive because data were not provided regarding lung fiber 

burdens and the frequency with which lesions were observed in the exposed and control groups. 

No significant respiratory effects were observed in female Wistar rats exposed nose-only to 252 WHO 

fibers/cc of Tempstran 475 (Code 104) glass fiber for 1 year (Muhle et al. 1987). This study represents 

the only animal inhalation NOAEL reported for a synthetic vitreous fiber. 

Two intermediate studies with unspecified types of glass wool reported cell lysis, suggesting that 

clearance mechanisms may have been overloaded (Johnson and Wagner 1980; Lee et al. 1981b). 

Exposure of Fischer rats to 10 mg/m3

 of a glass wool for 50 weeks caused focal fibrosis and pulmonary 

inflammation (localized bronchiolar and alveolar degeneration and hyperplasia, and lysis of debris-filled 

macrophages) (Johnson and Wagner 1980). Rats and guinea pigs exposed to 70 fibers/cc of a ball-milled 
 

SYNTHETIC VITREOUS FIBERS 92 

3. HEALTH EFFECTS 

(7% fiber) glass wool for 3 months exhibited pulmonary inflammation (hyperplasia and lysis of dustfilled lung cells [presumably macrophages], and a very slight increase in the incidence of ferruginous 

bodies [iron deposits]) that subsided within 6 months (Lee et al. 1981b). Apparently, no inflammation 

occurred in similarly exposed hamsters, but conclusions could not be drawn from the study due to limited 

reporting. 

A 2-year assay of four types of glass wool in female Osborne-Mendel rats and male Syrian Golden 

hamsters did not report any signs of nonmalignant respiratory effects (Smith et al. 1987). The results of 

this study are inconclusive, because reporting of study details was very limited. As such, NOAELs and 

LOAELs from this study are not included in Table 3-1 or Figure 3-1. The concentrations were 300 or 

3,000 fibers/cc of a 0.45 μm diameter glass (0.3 or 3.0 mg/m3

), 100 fibers/cc of a 3.1 μm diameter glass 

(10 mg/m3

), 10 or 100 fibers/cc of a 5.4 μm diameter glass (1.2 or 12 mg/m3), and 25 fibers/cc of 6.1 μm 

diameter glass (9 mg/m3

). 

In Wistar rats exposed for 2 years to a glass wool (concentration not specified), the reported signs were 

“simple alveolar macrophage reactions” and fibrosis (Le Bouffant et al. 1987). These effects were 

reported for all of the fibers tested (asbestos, glass wool, and rock wool). 

Rock Wool. No acute-duration rock wool inhalation studies in animals were identified. 

Two parallel studies, with intermediate and chronic timepoints, provide the most reliable information for 

the respiratory effects of MMVF21 and MMVF34/HT rock wool (Kamstrup et al. 1998, 2001; McConnell 

et al. 1994). MMVF21 is a traditional basalt-based, rock (stone) wool. MMVF34/HT is a more recently 

developed rock wool characterized as having a relatively high content of aluminum and low content of 

silica, compared with MMVF21. Supporting information is provided by an intermediate (Johnson and 

Wagner 1980) and a chronic (Le Bouffant et al. 1987) study. Pulmonary inflammation was seen for all of 

the rock wools tested; fibrosis was seen for MMVF21 (and unspecified types of rock wool), but not for 

MMVF34. 

In male Fischer 344 rats exposed nose-only to MMVF21 at concentrations of 34, 150, or 243 WHO 

fibers/cc (3.1, 16.1, or 30.4 mg/m3

) for up to 24 months with interim sacrifices, minimal pulmonary 

inflammation (increase in pulmonary macrophages) was seen at levels as low as 34 WHO fibers/cc 

(3.1 mg/m3

) by 3 months, and severity of the inflammatory response increased with increasing exposure 
 

 

SYNTHETIC VITREOUS FIBERS 93 

3. HEALTH EFFECTS 

level (Kamstrup et al. 2001; McConnell et al. 1994). For example, rats in the highest exposure group 

showed mild bronchiolization, in addition to increased pulmonary macrophages, by 3 months of 

exposure. Signs of minimal fibrosis (collagen deposition at the bronchoalveolar junction) were found in 

2/6 rats exposed to 264 WHO fibers/cc at 12 months of exposure. By 18 months of exposure, all rats 

exposed to 150 or 264 WHO fibers/cc showed signs of minimal or mild fibrosis (rats with mild fibrosis 

showed some interlobular linking), but the fibrosis was not more pronounced at these exposure levels 

after 24 months. 

In male Fischer 344 rats exposed nose-only to 291 WHO fibers/cc (30.1 mg/m3

) of MMVF34/HT, for up 

to 2 years, inflammation (increased absolute and relative lung weight, macrophage infiltration and 

microgranuloma formation, alveolar bronchiolization) was seen as early as 3 months (Kamstrup et al. 

1998, 2001). Minimal bronchoalveolar collagen deposition (a sign of fibrosis) was seen in a few rats at 

6 and 18 months, but was not observed in rats exposed for 12 or 24 months. As such, no clear and 

consistent signs of pulmonary fibrosis were found in rats exposed to 291 WHO fibers/cc of MMVF34/HT 

for up to 24 months. The results indicate that the newly developed rock wool, MMVF34/HT, is a less 

potent respiratory toxicant than the traditional rock wool, MMVF21. 

Exposure of Fischer rats to 10 mg/m3

 of an unspecified rock wool for 50 weeks reportedly caused focal 

fibrosis, localized bronchiolar and alveolar degeneration and hyperplasia, and lysis of debris-filled 

macrophages (Johnson and Wagner 1980). 

In Wistar rats exposed for 2 years to a rock wool (concentration not specified), the reported signs were 

“simple alveolar macrophage reactions” and fibrosis (Le Bouffant et al. 1987). These effects were 

reported for several fibers tested (asbestos, glass wool, and rock wool) in this study. 

Slag Wool. No acute-duration slag wool inhalation studies in animals were identified. Pulmonary 

inflammation, but no fibrosis, has been reported for slag wool. 

Male Fischer 344 rats exposed nose-only for 2 years to levels as low as 33 fibers/cc of MMVF22, a blastfurnace slag wool (30 WHO fibers/cc; 3.1 mg/m3

) exhibited minimal pulmonary inflammation by 

3 months (macrophage infiltration, microgranuloma development, and bronchiolization) (McConnell et 

al. 1994). The severity of these effects increased with increasing concentration and with longer exposure 

duration. No fibrosis or effects in the pleura were seen at levels up to 213 WHO fibers/cc (29.9 mg/m3

). 
SYNTHETIC VITREOUS FIBERS 94 

3. HEALTH EFFECTS 

Another study reported no fibrosis or bronchoalveolar metaplasia in female Osborne-Mendel rats or male 

Syrian Golden hamsters exposed for 2 years to 200 fibers/cc of a 2.7 μm diameter slag wool (10 mg/m3

) 

(Smith et al. 1987). This apparent NOAEL was not included in Table 3-1 or Figure 3-1 due to limiting 

reporting of experimental details and results for this study. 

Continuous Filament Glass. No inhalation studies in animals with continuous glass filaments were 

identified. Because this type of synthetic vitreous fiber most frequently has large diameters that render 

the fibers nonrespirable (ACGIH 2001; Lee et al. 1995), studies have focused on other routes of exposure 

(see Section 3.2.4). 

Other Fibers. Exposure of male Fischer 344 rats to high-silica synthetic vitreous fiber, X607, at a 

concentration of 180 WHO fibers/cc (equivalent to 30 mg/m3

), caused pulmonary inflammation 

(macrophage aggregation by 13 weeks, alveolar bronchiolization by 39 weeks, and macrophage 

microgranulation as early as 52 weeks), but no evidence of bronchioalveolar or pleural fibrosis even after 

2 years of exposure (Hesterberg et al. 1998b). X607 is a high-silica synthetic vitreous fiber with glasslike characteristics, which is produced using processes similar to those used for rock wool, slag wool, and 

refractory ceramic fibers. It has temperature resistance properties that are intermediate between those of 

insulation glass wools and refractory ceramic fibers (Hesterberg et al. 1998b). 

The highest reliable NOAEL values and all reliable LOAEL values for respiratory effects (and other 

systemic effects) in animals exposed by inhalation to synthetic vitreous fibers are summarized in 

Table 3-1 and plotted in Figure 3-1. 

Cardiovascular Effects. Analysis of cause-of-death information for 2,758 male workers (from a 

cohort of 11,373 men) included in the European cohort study found a statistically significant increase in 

mortality from ischemic heart disease among continuous filament workers (51 of 172 total deaths, 

standardized mortality ratio (SMR) of 1.22 with a 95% CI=1.06–1.88), but not among workers exposed to 

glass or rock and slag wool (mean SMRs of 1.05, and 0.97, respectively) (Sali et al. 1999). Among rock 

and slag wool workers, the trend for increased risk of mortality from ischemic heart disease correlated 

significantly with age. No elevations of risk for mortality from diseases of the circulatory system or 

cerebrovascular disease were observed (SMR ranged from 0.99 to 1.22 and from 0.95 to 1.21, 

respectively). The results from this study do not clearly establish an association between increased risk of 
 

SYNTHETIC VITREOUS FIBERS 95 

3. HEALTH EFFECTS 

death from ischemic heart disease and occupational exposure during the manufacture of continuous 

filament glass, due to the lack of measures of confounding influences on ischemic heart disease such as 

heat, other chemical exposures in the workplace such as carbon monoxide, and physical strain. 

The risk of death from cardiovascular diseases related to occupational exposure to continuous glass fibers, 

glass wool, and rock and slag wool were not increased significantly in either the U.S. cohort study (Marsh 

et al. 2001a) or the Canadian studies (Shannon et al. 1987, 1990). 

Some intermediate- and chronic-duration animal studies conducted routine heart histopathology, but did 

not find any adverse effects (see Table 3-1). 

Gastrointestinal Effects. The majority of synthetic vitreous fibers that are deposited in the 

respiratory tract during inhalation exposure are transported by mucociliary action to the pharynx, where 

they are swallowed (see Section 3.4). Consequently, the gastrointestinal epithelium is also directly 

exposed to fibers as a result of inhalation exposure. 

Despite this exposure, inhalation exposure to continuous glass filament, glass wool, and rock and slag 

wool were not associated with increased risk of mortality from diseases of the digestive tract in the death 

records of 9,060 workers (from a cohort of 32,110) in the U.S. study (Marsh et al. 2001a), 2,758 male 

workers (from a cohort of 11,373 men) in the IARC study (Sali et al. 1999), 157 insulating glass wool 

workers (from a cohort of 2,557) in Sarnia, Canada (Shannon et al. 1984, 1987), 96 continuous glass 

filament workers (from a cohort of 1,465) in Guelph, Canada (Shannon et al. 1990), or 554 prefabricated 

houses builders (from a cohort of 1,068) in Sweden with glass and rock wool exposure (Gustavsson et al. 

1992). 

Some intermediate- and chronic-duration animal studies did not find any adverse histopathologic changes 

in the gastrointestinal tracts (see Table 3-1). 

Hepatic Effects. The European cohort study reported that mortality from cirrhosis of the liver was 

significantly increased among continuous filament workers (12 of 172 total deaths, SMR=2.12, 95% 

CI=1.10–3.71), but not among workers exposed to glass or rock and slag wool (mean SMRs of 0.99 and 

1.10, respectively) (Sali et al. 1999). The cause for this slight increase is unclear, but may be related to 

confounding factors related to lifestyle. Cause-of-death information for 2,758 workers (from a cohort of 
SYNTHETIC VITREOUS FIBERS 96 

3. HEALTH EFFECTS 

11,373 men) was analyzed. In contrast, the number of mortalities caused by liver cirrhosis was 

significantly decreased among the total U.S. cohort compared to national (but not local county) rates 

(SMRs of 0.68 and 0.88, respectively) (Marsh et al. 2001a). A smaller study analyzing 554 deaths from a 

cohort of 1,068 prefabricated house builders found no correlation between liver cirrhosis and exposure to 

glass and rock wool (Gustavsson et al. 1992). 

Some intermediate- and chronic-duration animal studies conducted routine liver histopathology but did 

not report any adverse effects (see Table 3-1). 

Renal Effects. No relationship between occupational exposure to rock and slag wool, glass wool, or 

continuous filament and mortality from nonmalignant renal disease has been detected in occupational 

cohort studies in the United States (Marsh et al. 2001a), European (Sali et al. 1999), or Swedish 

(Gustavsson et al. 1992) cohorts. Data for mortality from nonmalignant renal disease were not reported 

for the Canadian cohorts (Shannon et al. 1987, 1990). 

Some intermediate- and chronic-duration animal studies conducted routine kidney histopathology, but did 

not find any adverse effects (see Table 3-1). 

No reliable studies were located regarding the following effects in humans or animals after inhalation 

exposure to synthetic vitreous fibers: 

3.2.1.3 Immunological and Lymphoreticular Effects 

3.2.1.4 Neurological Effects 

3.2.1.5 Reproductive Effects 

3.2.1.6 Developmental Effects 

3.2.1.7 Cancer 

The principal target organs of concern for cancer are the lungs (bronchoalveolar adenoma and carcinoma) 

and the pleura (mesothelioma). Single layers of mesothelial cells compose the pleura, the delicate serous 

membrane that covers the lungs (visceral pleura) and chest wall and diaphragm (parietal pleura), as well 
SYNTHETIC VITREOUS FIBERS 97 

3. HEALTH EFFECTS 

as the peritoneum, the membrane lining the abdominal walls and viscera. Mesotheliomas are rare 

malignant tumors of mesothelial cells; their incidence in the general human population is low, and pleural 

mesotheliomas have not been observed in control animals. 

Available epidemiological results provide inadequate evidence of the carcinogenicity of synthetic vitreous 

fibers in humans (see below). Animal studies have detected elevated incidences of lung tumors and the 

formation of mesotheliomas following exposure to refractory ceramic fibers and two other fiber types 

(e.g., special-purpose glass microfiber 104E-glass and MMVF33, a durable special purpose glass fiber), 

but not for other synthetic vitreous fibers, such as traditional building insulation glass wools, that are less 

biopersistent (see below and Section 3.5). 

Intermediate-duration (1-year) exposure of male Wistar rats to special purpose 104E-glass fibers was 

associated with a statistically significant increase in the combined (but not individual) incidence of lung 

adenomas and carcinomas (Cullen et al. 2000). Chronic exposure of male Fischer 344 rats to refractory 

ceramic fibers, RCF1 or RCF3, was associated with statistically significant elevations in lung adenoma 

and carcinoma incidence, and exposure to RCF2 was associated with increased lung carcinoma (but not 

adenoma) incidence (Mast et al. 1995a). In contrast, RCF1 did not induce lung tumors in male Syrian 

Golden hamsters (McConnell et al. 1995). The discrepancy between the two studies may be related to 

species specificity or differences in exposure duration (24 months for rats, 18 months for hamsters). No 

increased lung tumor incidence was reported in intermediate-duration studies with 100/475 specialpurpose glass microfiber (Cullen et al. 2000), Code 104/475 special purpose glass fiber (Muhle et al. 

1987), or GB100R glass wool (Haratake et al. 1995) in rodents or in chronic-duration studies with 

MMVF10, MMVF11 (Hesterberg et al. 1993c), MMVF21, MMVF22 (McConnell et al. 1994), MMVF33 

(McConnell et al. 1999), MMVF34 (Kamstrup et al. 2001), or X607 fiber (Hesterberg et al. 1998b) in 

rodents or with C102/C104 blend fibrous glass in baboons (Goldstein et al. 1983). 

Only one study has observed a statistically significant increase in pleural mesotheliomas, in male Syrian 

Golden hamsters exposed to 215 WHO fibers/cc of RCF1 for 18 months (42/102 versus 0/106 for 

controls) (McConnell et al. 1995); mesotheliomas were first seen at 40 weeks. Other studies have 

detected one or two mesotheliomas per treatment group among rats exposed to 1,022 WHO fibers/cc of 

104E-glass for 1 year (Cullen et al. 2000), rats exposed for 2 years to 75 or 220 (but not 120) WHO 

fibers/cc of RCF1, as well as RCF2, RCF3, or RCF4 (220, 182, or 153 WHO fibers/cc, respectively) 
SYNTHETIC VITREOUS FIBERS 98 

3. HEALTH EFFECTS 

(Mast et al. 1995a, 1995b), and hamsters exposed to 310 WHO fibers/cc of MMVF33, a durable special 

purpose glass fiber, for 18 months (McConnell et al. 1999). 

Human Studies. 

Refractory Ceramic Fibers. In a recent initial report of a cohort mortality study of male workers 

employed at two U.S. refractory ceramic fiber manufacturing plants between 1952 and 2000 (LeMasters 

et al. 2003), the only statistically significant excess mortality was deaths associated with cancer of the 

urinary system. As of December 31, 2000, a total of 87 deaths were recorded among the 942 men 

(average age=51 years) included in the study (about 9% of the cohort). Observed number of deaths and 

SMRs for selected cancer-related deaths were as follows (with 95% CI noted in parentheses): all cancers, 

29 deaths, SMR=94.2 (63–135); malignancies of the respiratory system, 9 deaths, SMR=78.8 (36–150); 

and malignancies of the urinary system, 5 deaths, SMR=344.8 (112–806). No mesotheliomas were 

identified among the cohort to date, based on careful review of death certificates, medical records, and 

lung tissue analysis. LeMasters et al. (2003) noted that the finding for excess urinary cancer deaths may 

be a chance finding given the wide confidence interval for the SMR, the large number of statistical tests 

that were conducted (n=46), and the lack of a plausible mechanistic explanation of how fibers may 

increase the risk for urinary cancer mortality. Continued monitoring of the mortality experience of this 

cohort is planned. 

Glass Wool, Rock and Slag Wool, and Continuous Filament Glass Fibers. Major cohort mortality and 

nested case-control studies of groups of workers engaged in the production of filament glass fibers, glass 

wool, rock wool and slag wool are ongoing in the United States (Bayliss et al. 1976; Buchanich et al. 

2001; Chiazze et al. 1992, 1993, 1995, 1997, 2002; Enterline and Henderson 1975; Marsh et al. 1990, 

2001a, 2001b, 2001c; Morgan 1981; Quinn et al. 2001; Robinson et al. 1982; Smith et al. 2001; Stone et 

al. 2001; Watkins et al. 1997; Wong et al. 1991; Youk et al. 2001) and Europe (Andersen and Langmark 

1986; Bertazzi et al. 1986; Boffetta et al. 1997, 1999; Claude and Frentzel-Beyme 1984, 1986; Khaerheim 

et al. 2002; Lea et al. 1999; Olsen and Jensen 1984; Olsen et al. 1986; Plato et al. 1995c; Sali et al. 1999; 

Saracci et al. 1984; Simonato et al. 1986a, 1987; Teppo and Kojonen 1986; Westerholm and Bolander 

1986). Smaller studies have been conducted in Canada (Shannon et al. 1984, 1987, 1990), Sweden 

(Gustavsson et al. 1992; Plato et al. 1997), and the United States (Bayliss et al. 1976; Enterline and 

Henderson 1975; Morgan 1981; Robinson et al. 1982). These studies provide inadequate evidence of 

carcinogenicity in humans with occupational exposure. Although some small, statistically significant 
SYNTHETIC VITREOUS FIBERS 99 

3. HEALTH EFFECTS 

elevations in respiratory system cancer risk were detected, the lack of sufficient data regarding potential 

confounding factors prevents a conclusive determination that the increased risks were due to these 

synthetic vitreous fibers (see below). 

Early studies of U.S. fibrous glass production workers did not associate exposure to fibrous glass or rock 

and slag wool with increased risk of respiratory or other cancers (Bayliss et al. 1976; Enterline and 

Henderson 1975; Morgan 1981; Robinson et al. 1982), but lacked statistical power due to their small size 

(cohorts of <1,500 men and cause-of-death information obtained for <400 workers). A larger study 

analyzed mortality statistics for workers from 17 U.S. plants manufacturing either fiberglass (glass wool 

or continuous filament glass) or rock wool and slag wool from the 1940s to the 1980s; it was conducted 

by the University of Pittsburgh under the sponsorship of the Thermal Insulation Manufacturers 

Association (TIMA), analyzing mortality statistics from the 1940s to the 1980s (Chiazze et al. 1992, 

1993, 1995, 1997, 2002; Enterline 1990; Enterline et al. 1983, 1987; Marsh et al. 1990; Watkins et al. 

1997; Wong et al. 1991); the results found either none or small and occasionally statistically significant 

elevations in the risk for respiratory system cancer among glass wool and rock and slag wool workers, but 

observed no correlation between length of exposure and increased risk. To overcome limitations in these 

initial studies, a comprehensive surveillance of the U.S. cohort was performed by the University of 

Pittsburgh under the sponsorship of the North American Insulation Manufacturer’s Association (NAIMA) 

(Buchanich et al. 2001; Marsh et al. 2001a, 2001b, 2001c; Quinn et al. 2001; Smith et al. 2001; Stone et 

al. 2001; Youk et al. 2001). Mortality data collected until 1992 for 9,060 workers from a cohort of 

32,110 workers in the 10 largest and longest-operating factories were analyzed (Marsh et al. 2001a). The 

mean exposure to respirable fibers was estimated at 0.073 fibers/cc. A small, but statistically significant, 

increase in the SMR for respiratory system cancer was limited to workers employed <5 years (SMR=1.12, 

95% CI=1.01–1.24), suggesting an exposure-independent “healthy worker” effect. No patterns or 

statistically significant trends associated increasing risk for respiratory system cancer mortality with 

increasing measures of exposure (years of employment or estimated cumulative exposure). A nested-case 

control analysis (632 cases, 572 controls) did not observe any relationship between respiratory system 

cancer risk and exposure indices (Marsh et al. 2001a; Youk et al. 2001). 

The IARC began a large international cohort study of European workers involved in the manufacture of 

synthetic vitreous fibers in 1976. The study includes 13 factories that produced glass wool, continuous 

glass filament, or rock and slag wool in Denmark, Finland, Norway, Sweden, the United Kingdom, 

Germany, and Italy. Early reports frequently focused on data from single countries (Andersen and 
 

SYNTHETIC VITREOUS FIBERS 100 

3. HEALTH EFFECTS 

Langmark 1986; Bertazzi et al. 1986; Claude and Frentzel-Beyme 1984, 1986; Olsen and Jensen 1984; 

Olsen et al. 1986; Plato et al. 1995c; Teppo and Kojonen 1986; Westerholm and Bolander 1986) going 

back as far as the 1930s. The ongoing European study has incorporated these data and has published 

follow-up reports for data collected through the 1980s (Boffetta et al. 1992; Gardner et al. 1986, 1988; 

Saracci et al. 1984; Simonato et al. 1986a, 1987) and early 1990s (Lea et al. 1999; Sali et al. 1999), with 

the most recent reports considering data up to 1995 (Boffetta et al. 1997, 1999). Most recently, cause-ofdeath information for 4,521 workers (191 continuous filament workers from two factories, 1,679 glass 

wool workers from five factories, and 1,281 rock and slag wool workers from seven factories) was 

analyzed from a cohort of 22,002 individuals (Boffetta et al. 1997). No increased risk of cancer incidence 

was clearly related to exposure, and none were related to duration of employment or time since first 

employment. Among glass wool workers, a statistically significant overall increase (SMR=1.27, 95% 

CI=1.07–1.50) in mortality from cancers of the trachea, bronchus, and lung did not persist either when 

local mortality rates were used or when workers with <1 year of employment were excluded (a national 

healthy worker effect). The increase of mortality from lung cancer among continuous filament workers 

(SMR=1.11, 95% CI=0.61–1.86) was not significant overall and was attributed to one factory in Italy. 

Potential exposure to asbestos was associated with a significant increase (SMR=1.69, 95% CI=1.22–2.29) 

in the risk of lung cancer among all workers. A statistically significant increase (SMR=1.34, 95% 

CI=1.08–1.63) in the SMR for risk of death from cancers of the trachea, bronchus, and lung for all rock 

and slag wool workers was attributed to one factory in Germany where exposure to asbestos was reported. 

After exclusion of that factory, no significant elevation in risk remained (SMR=1.16, 95% CI=0.87–1.51) 

for rock and slag wool workers. The authors concluded that “these results are not sufficient” to conclude 

that exposure to synthetic vitreous fibers increased the risk of lung or other cancer types. 

Because cancer incidence may be a more sensitive tool than mortality incidence for the detection of 

adverse health effects, a cancer incidence study of the European cohort was conducted (Bofetta et al. 

1999). Data were obtained from the national cancer registrations of Denmark, Finland, Norway, and 

Sweden for 3,685 rock and slag wool workers and 2,611 glass wool workers who had been employed for 

at least 1 year in one of nine factories in between 1933 and 1995. Although the elevation for cancers of 

the oral cavity and pharynx was statistically significant (27 cases, standard incidence ratio [SIR]=1.84, 

95% CI=1.22–2.68) for slag wool workers, the combined incidence of cancers of the oral cavity, pharynx, 

and larynx combined was not significant (31 cases, SIR=1.46, 95% CI=0.99–2.07). Among glass wool 

workers, these incidences were not significantly elevated (11 cases, SIR=1.31, 95% CI=0.65–2.34 and 

16 cases, SIR=1.41, 95% CI=0.80–2.28, respectively) but the trend between increasing time since first 
SYNTHETIC VITREOUS FIBERS 101 

3. HEALTH EFFECTS 

employment working with glass wool and increased incidences of oral, pharyngeal, and laryngeal cancers 

was statistically significant. The authors concluded that these data were inadequate evidence of 

carcinogenicity because potential effects from confounding factors such as smoking had not been 

included. 

In a nested case-control study of 133 lung cancer cases and 513 matched controls among men who 

worked in seven rock and slag wool manufacturing plants in Denmark, Norway, Sweden, or Germany, no 

statistically significant associations with exposure were found (Kjaerheim et al. 2002). Occupational 

exposure was assessed on the basis of interview data and exposure information from the manufacturing 

plants; cases and controls were placed in quartile categories of exposure. Smoking-adjusted odds ratios 

for workers with at least 15 years since first exposure showed no evidence of increasing odds ratio with 

increasing category of cumulative exposure; odds ratios for the second, third, and fourth quartiles of 

cumulative exposure (with 95%CI noted in parentheses) were 1.3 (0.7–2.3), 1.0 (0.5–1.9), and 0.7 (0.3– 

1.3), respectively. Similar results were obtained with other exposure metrics and after controlling for 

other potential confounders. 

Two mortality studies were conducted in Canada, using mortality data collected from the national Vital 

Statistics and Disease Registry. An initial (Shannon et al. 1984) and follow-up (Shannon et al. 1987) 

study obtained information for 157 male workers employed between 1955 and 1977 for at least 90 days at 

an insulating glass wool manufacturing plant in Sarnia, Ontario, Canada. In 1978, the mean concentration 

of glass wool fibers with diameters <3.5 μm in the plant was 0.1 fiber/cc, but the authors believed that 

earlier concentrations had been higher. A statistically significant increase (SMR=1.99, 95% CI=1.28– 

3.11) for mortality from lung cancer was detected among exposed employees based on an observed 

19 deaths versus 9.5 expected. However, four of these deaths occurred in men with <1 year of exposure, 

and cancer risk was not elevated in people with at least 5 years of exposure. Because increasing length of 

exposure did not correlate with increasing risk or decreased latency, the authors considered the results 

inconclusive. The other mortality study identified 96 deaths from a cohort of workers who had been 

employed for at least 1 year between 1951 and 1986 at a glass filament plant in Guelph, Ontario, Canada 

(Shannon et al. 1990). The mean number of fibers in dust samples collected at that plant between 

1979 and 1987 reportedly ranged from 0.02 to 0.5 fibers/cc with values as high as 0.91 fibers/cc, but the 

proportion of glass fibers was not determined. No significant difference in lung cancer mortality was 

seen. For both Canadian studies, no other differences in cancer mortality incidence were significant (all 
 

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3. HEALTH EFFECTS 

cancers combined, cancer of the digestive system and peritoneum, cancer of the genito-urinary organs, 

lymphatic and hepatopoietic malignancies), and data were not adjusted for smoking habits. 

European case-control studies of lung cancer, multiple myeloma, mesothelioma, and cancers of the larynx 

and hypopharynx conducted separately from the European cohort mortality study have been inconclusive 

due to relatively few cases exposed to synthetic vitreous fibers without confounding exposures (BrueskiHohlfeld et al. 2000; Lee et al. 2003; Marchand et al. 2000; Pohlabeln et al. 2000; Rodelsperger et al. 

2001). Exposure was estimated by employment information collected from questionnaires, and the 

potential for co-exposure to asbestos was a confounding factor. An analysis of pooled lung cancer 

incidence data collected in Germany (1988–1993 and 1990–1996) identified only 51 cases and 

28 matched controls (identified from a national mandatory registry of residents) who had been exposed to 

glass wool or mineral wool (as insulators in the construction industry) without asbestos co-exposure 

(Brueski-Hohlfeld et al. 2000; Pohlabeln et al. 2000); after adjustment for smoking, this difference was 

not statistically significant (OR=1.56, 95% CI=0.92–2.65). No statistically significant association 

between occupational exposure to mineral wool and multiple myeloma was found in a case-control study 

of 446 cases of multiple myeloma among Swedish construction workers (Lee et al. 2003). A German 

case-control study for mesothelioma was inconclusive because only two cases of diffuse malignant 

mesothelioma and two controls (matched from a national mandatory registry of residents) who had been 

exposed to synthetic mineral fibers, but not asbestos, were identified from a total of 125 cases and 

125 controls (Rodelsperger et al. 2001). A French case-control study for squamous cell carcinoma of the 

larynx or hypopharynx did not associate exposure to exposures to mineral wool (OR=1.33, 95% CI=0.91– 

1.95 and OR=1.55, 95% CI=0.99–2.41), glass filaments (OR=0.44, 95% CI=0.15–1.31 and OR=0.91, 

95% CI=0.30–2.76), or ceramic fibers (OR=1.28, 95% CI=0.51–3.22 and OR=0.78, 95% CI=0.26–2.38) 

to increased risks of these cancers in 528 cases and 205 controls (hospital patients with nonmalignant 

respiratory disease) (Marchand et al. 2000). 

Small studies of exposure in other occupations have also been inconclusive. A cohort study of 

1,342 unexposed workers and 1,068 workers exposed to glass and rock wool in the production of 

prefabricated houses in 11 Swedish plants did not detect any statistically significant elevation in risk of 

mortality from any type of cancer (Gustavsson et al. 1992). The study assigned three categories of 

exposure: the mean for 478 men was 0.11 fibers/cc (range 0.05–0.17 fibers/cc), for 375 men was 

0.09 fibers/cc (range 0.05–0.13 fibers/cc), and for 215 men was 0.06 fibers/cc (range 0.02–0.08 fibers/cc). 

Another cohort study of 2,807 workers (including 478 insulators, the occupation with highest exposure) 
SYNTHETIC VITREOUS FIBERS 103 

3. HEALTH EFFECTS 

in the Swedish prefabricated house industry observed no increased risk of lung cancer (for the general 

cohort, SMR=0.56, 95% CI=0.45–1.44; for insulators, SMR=0.85, 95% CI=0.01–3.01) associated with 

exposure to synthetic vitreous fibers (not specified, presumably glass wool) (Plato et al. 1997). The mean 

exposure to synthetic vitreous fibers (not specified, presumably glass wool) was 0.14 fibers/cc; insulators, 

as high as 0.18 fibers/cc (Plato et al. 1997). 

In summary, studies of workers involved in the manufacture of continuous glass filament, glass wool, and 

rock and slag wool provide inadequate evidence for carcinogenicity in humans. A number of reviews of 

the fibrous glass cohort mortality and case-control studies concur with this conclusion (ACGIH 2001; 

Hesterberg and Hart 2001; IARC 1988, 2002; Lee et al. 1995; NIOSH 1977; NRC Subcommittee on 

Manufactured Vitreous Fibers 2000; Wilson et al. 1999). No evidence has associated inhalation exposure 

to these materials with nonrespiratory cancers. 

Animal Studies. 

Refractory Ceramic Fibers. Studies conducted in rats and hamsters have associated inhalation exposure 

to refractory ceramic fibers with mesothelioma formation and increased incidences of lung adenomas and 

carcinomas (Davis et al. 1984; Hesterberg et al. 1998b; Mast et al. 1995a, 1995b; McConnell et al. 1995; 

Smith et al. 1987). 

Two studies relevant to intermediate-duration exposure were identified. Exposure of Wistar rats to 

95 WHO fibers/cc of a ceramic aluminum silicate glass for 12 months followed by a 20-month 

observation period was associated with a statistically significant increase in the combined incidence of 

respiratory tumors (one adenoma, three carcinomas, and four malignant histiocytomas in a group of 

48 rats) compared to controls (no observed tumors in 40 rats) (Davis et al. 1984). Additionally, one 

peritoneal mesothelioma was identified; the relevance of this tumor outside the pleural cavity is unclear, 

but it might represent a metastasis of an occult lesion. A chronic study that exposed male Syrian Golden 

hamsters exposed to 215 WHO fibers/cc (30 mg/m3

) of RCF1 for up to 18 months detected mesotheliomas in animals that reportedly died from other (noncancer) causes: 2 at 40 weeks, 1 at 45 weeks, 

and 1 at 47 weeks (McConnell et al. 1995). Additionally, a mesothelioma (1/3) was observed in the 

interim-sacrifice group euthanized at 12 months (McConnell et al. 1995). At study termination, no lung 

adenomas or carcinomas were seen in control or exposed animals (0/106, 0/102). However, the 
SYNTHETIC VITREOUS FIBERS 104 

3. HEALTH EFFECTS 

incidences of mesothelial cell hypertrophy (0/106 versus 33/102) and pleural mesothelioma (0/106 versus 

42/102) were significantly increased. 

Other chronic studies have also found evidence of carcinogenicity. No lung tumors were seen in male 

Fischer 344 rats exposed nose-only to RCF1 at concentrations as high as 120 WHO fibers/cc (17 mg/m3

) 

for 2 years, although a single mesothelioma was seen at 75 WHO fibers/cc (Mast et al. 1995b). A 

companion 2-year study exposed male Fischer 344 rats nose-only to single concentrations of RCF1, 

RCF2, RCF3, or RCF4 (187, 220, 182, or 153 WHO fibers/cc; 30 mg/m3

 for each) (Mast et al. 1995a). 

The first three concentrations induced statistically significant increases in the incidences of bronchiolaralveolar hyperplasia (control 5/130; 17/123, 15/121, 15/121, and 8/118 for RCF1, RCF2, RCF3, and 

RCF4, respectively) and pulmonary carcinoma (control 0/130; 8/123, 5/121, 9/121, and 2/118 for RCF1, 

RCF2, RCF3, and RCF4, respectively). Only RCF1 and RCF3 significantly induced pulmonary 

adenomas (control 2/130; 8/123, 5/121, 9/121, and 2/118 for RCF1, RCF2, RCF3, and RCF4, 

respectively). Although the incidences were not statistically significant, mesotheliomas were detected for 

RCF1, RCF2, and RCF3 (but not RCF4) (control 0/130; 2/120, 3/123, 2/121, 0/118 for RCF1, RCF2, 

RCF3, and RCF4, respectively). Data from the 2-year bioassays with male Fischer 344 rats exposed to 

RCF1 (Mast et al. 1995a, 1995b) provide the best available data describing exposure-response 

relationships for cancer and chronic exposure to refractory ceramic fibers; however, the presence of nonfibrous particles in the RCF1 test atmosphere is widely acknowledged to have added to the noncancer and 

cancer responses to an undetermined degree (Bellmann et al. 2001; Mast et al. 2000; Maxim et al. 2003b). 

Under conditions in which lung clearance mechanisms become overloaded, many types of nonfibrous or 

fibrous materials can produce pulmonary fibrosis or tumors in rats (Oberdörster 1994). 

A mesothelioma was also found in male Syrian Golden hamsters exposed to 200 fibers/cc (12 mg/m3

) of 

an unspecified type of refractory ceramic fiber for 2 years (Smith et al. 1987). No lung tumors were 

observed in these hamsters, or in similarly-treated female Osborne-Mendel rats. The study was 

inconclusive because the positive control (crocidolite asbestos) failed to induce lung tumors and reporting 

of experimental details was limited. 

In summary, different samples of refractory ceramic fibers induced lung tumors in rats and mesotheliomas in both hamsters and rats. These results have demonstrated the carcinogenicity of refractory 

ceramic fibers in animals following inhalation exposure, and indicate that fiber type and exposure levels 

are important factors influencing carcinogenicity. It should be noted that the degree to which nonfibrous 
SYNTHETIC VITREOUS FIBERS 105 

3. HEALTH EFFECTS 

particles in RCF1 may have contributed to the carcinogenic responses in RCF1-exposed rats (Mast et al. 

1995a, 1995b) is undetermined. 

Glass Wool (Insulation Glass Wools and Special Purpose Glass Fibers). Mesothelioma formation has 

been found in one chronic rat study with MMVF33, a durable special purpose glass fiber (Hesterberg et 

al. 1999) and another rat study involving 1-year exposures to special purpose 104E-glass fiber (Cullen et 

al. 2000). No mesotheliomas were found in rats exposed to the insulation glass wools, MMVF10 or 

MMVF11 (Hesterberg et al. 1993), or in hamsters exposed to MMVF10a (McConnell et al. 1999). 

Exposure to special purpose 104E-glass fiber also induced increased incidences of lung tumors in rats 

(Cullen et al. 2000). In contrast, inhalation studies with MMVF33 and the insulation glass wools, 

MMVF10, MMVF11, and C102/C104 fibrous glass blend, did not find exposure-related increases in lung 

tumor incidence (Goldstein et al. 1983; Haratake et al. 1995; Johnson and Wagner 1980; Kamstrup et al. 

1998, 2001; McConnell et al. 1994, 1999; Muhle et al. 1987; Smith et al. 1987). 

Intermediate-duration experiments did not provide evidence of carcinogenicity. No increased lung tumor 

incidence was found in female Wistar rats exposed nose-only to 252 fibers/cc (3 mg/m3

) of Code 104/475 

special purpose glass fiber for 1 year (Muhle et al. 1987) or in small experiments (<16 animals/exposure 

group) with male Wistar rats exposed to 2.2 mg/m3

 of a glass wool (fiber counts not reported) for 1 year 

(Haratake et al. 1995), or rats, hamsters, and guinea pigs exposed to 70 fibers/cc of a ball-milled 

fiberglass (7% fiber) for 3 months (Lee et al. 1981b), with post-exposure periods up to 1 year. 

In male Wistar rats exposed whole-body to 1,022 WHO fibers/cc of special purpose 104E-glass fiber for 

1 year followed by a 1-year recovery period, the combined lung tumor incidence was statistically 

significantly different from controls (3/43 versus 1/38 adenomas and 7/42 versus 1/38 carcinomas, 

respectively) (Cullen et al. 2000); additionally, one mesothelioma was induced (1/43 versus 0/38 for 

controls). Exposure of rats to 1,119 WHO fibers/cc of special purpose glass fiber code 100/475 using the 

same protocol did not induce any mesotheliomas or statistically significantly increased incidences of lung 

tumors (Cullen et al. 2000). 

One pleural mesothelioma (1/83 versus 0/83 for controls) and no lung tumors were observed in male 

Syrian Golden hamsters exposed to 310 WHO fibers/cc (37 mg/m3

) of MMVF33, a durable special 

applications glass fiber for 18 months (Hesterberg et al. 1999). No lung tumors or mesotheliomas were 

observed in male Syrian Golden hamsters exposed to 339 WHO fibers/cc (29.6 mg/m3

) of MMVF10a 
 

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3. HEALTH EFFECTS 

glass wool (a low fluorine preparation of MMVF10) for 18 months (McConnell et al. 1999). No lung 

tumors and no increased incidences of bronchoalveolar metaplasia were seen in male Syrian Golden 

hamsters or female Osborne-Mendel rats exposed for 2 years to 300 or 3,000 fibers/cc of a 0.45 μm 

diameter glass wool (0.3 or 3.0 mg/m3

), 100 fibers/cc of a 3.1 μm diameter glass wool (10 mg/m3), 10 or 

100 fibers/cc of 5.4 μm diameter glass wool (1.2 or 12 mg/m3

), 25 fibers/cc of 6.1 μm diameter glass 

wool (9 mg/m3

), or 200 fibers/cc of a 2.7 μm diameter slag wool (10 mg/m3) (Smith et al. 1987). 

Similarly, tumor incidence was not elevated in male Fischer 344 rats exposed nose-only to three 

concentrations of MMVF10 or MMVF11 glass wool for 2 years (Hesterberg et al. 1993c). MMVF10 was 

tested at 29, 145, and 232 WHO fibers/cc (3.1, 17.1, and 27.8 mg/m3

) and MMVF11 was tested at 41, 

153, and 246 WHO fibers/cc (4.8, 15.8, and 28.3 mg/m3

). 

No tumors were seen in biopsies collected at 8, 18, and 30 months (2/animals per time point) from a 

group of 10 male baboons (Papio ursinus) exposed to 1,122 NIOSH fibers (lengths >5 μm)/cc of a blend 

of C102 and C104 fibrous glass wools (7.54 mg/m3

; 5.80 mg/m3 respirable) for 35 months (Goldstein et 

al. 1983). The study was inconclusive because of the small numbers used and the small amount of tissue 

available for analysis. 

Slag Wool. The limited animal inhalation studies identified for slag wool did not provide any evidence of 

carcinogenicity. 

No lung tumors and no increased incidences of bronchoalveolar metaplasia were seen in male Syrian 

Golden hamsters or female Osborne-Mendel rats exposed for 2 years to 200 fibers/cc of a 2.7 μm 

diameter slag wool (10 mg/m3

) (Smith et al. 1987). 

In male Fischer 344 rats exposed nose-only for 24 months to 30, 131, or 213 WHO fibers/cc (3.1, 16.1, or 

29.9 mg/m3

) of MMVF22, a blast-furnace slag wool, no significant increases were seen in the individual 

or combined incidences of pulmonary adenoma or pulmonary carcinoma (McConnell et al. 1994). 

Rock Wool. The limited animal studies identified for rock wool did not provide any evidence of 

carcinogenicity. 

No tumors were reported in Fischer rats exposed to 10 mg/m3

 of rock wool (fiber count not reported) for 

50 weeks and allowed to recover for 4 months prior to sacrifice (Johnson and Wagner 1980). 
SYNTHETIC VITREOUS FIBERS 107 

3. HEALTH EFFECTS 

In male Fischer 344 rats exposed nose-only for 24 months to 34, 150, or 243 WHO fiber/cc (3.1, 16.1, or 

30.4 mg/m3

) of MMVF21, a traditional basalt-based rock (stone) wool, no significant increases were seen 

in the individual or combined incidences of pulmonary adenoma or pulmonary carcinoma (McConnell et 

al. 1994). Similarly, in male Fischer 344 rats exposed nose-only to 291 WHO fibers/cc (30.1 mg/m3

) of 

MMVF34/HT, a newly developed high-temperature rock wool, for 2 years (6 hours/day, 5 days/week), 

lung tumor incidence was not significantly increased (Kamstrup et al. 1998, 2001). 

Continuous Filament Glass. No inhalation cancer studies in animals with continuous glass filaments 

were identified. Because these fibers are not normally respirable (ACGIH 2001; Lee et al. 1995), studies 

have been limited to injection and implantation (see Section 3.2.4, Other Routes of Exposure). 

Other Fibers. No mesotheliomas or increased incidences of lung adenomas (1/121 versus 2/130 for 

controls or lung carcinomas (1/121 versus 0/130 for controls) were seen in male Fischer 344 rats exposed 

to 180 WHO fibers/cc (30 mg/m3

) of X-607 (Hesterberg et al. 1998b). 

3.2.2 Oral Exposure 

3.2.2.1 Death 

No studies were located regarding death in humans or animals after oral exposure to synthetic vitreous 

fibers. 

3.2.2.2 Systemic Effects 

No studies were located regarding respiratory, cardiovascular, gastrointestinal, hematological, musculoskeletal, hepatic, renal, endocrine, dermal, ocular, body weight, or metabolic effects in humans or animals 

after oral exposure to synthetic vitreous fibers. 
SYNTHETIC VITREOUS FIBERS 108 

3. HEALTH EFFECTS 

No studies were located regarding the following effects in humans or animals after oral exposure to 

synthetic vitreous fibers: 

3.2.2.3 Immunological and Lymphoreticular Effects 

3.2.2.4 Neurological Effects 

3.2.2.5 Reproductive Effects 

3.2.2.6 Developmental Effects 

3.2.2.7 Cancer 

3.2.3 Dermal Exposure 

3.2.3.1 Death 

No studies were located regarding death in humans or animals after dermal exposure to synthetic vitreous 

fibers. 

3.2.3.2 Systemic Effects 

No studies were located regarding respiratory, cardiovascular, gastrointestinal, hematological, 

musculoskeletal, hepatic, renal, endocrine, or body weight effects in humans or animals after dermal 

exposure to synthetic vitreous fibers. 

Dermal Effects. Strong itching and contact dermatitis (with erythema, maculae, papules, and other 

eczematous symptoms) have been associated with occupational exposure to synthetic vitreous materials, 

including glass wool insulation and fiberglass fabrics (Bendsoe et al. 1987; Bjornberg 1985; Bjornberg et 

al. 1979a, 1979b, 1979c; Fisher 1982; Fisher and Warkentin 1969; Heisel and Hunt 1968; Koh and Khoo, 

1995; Longely and Jones 1966; Minamoto et al. 2002; Possick et al. 1970; Stam-Westerveld et al. 1994; 

Tarvainen et al. 1993), rock wool (Bjornberg and Lowhagen 1977; Eun et al. 1991; Fisher 1982; KiecSwierczynska and Szymczk 1995; Peterson and Sabroe 1991; Thriene et al. 1996), and refractory ceramic 

fibers (Kiec-Swierczynska and Wojtczak 2000). The skin irritation has been associated with fibers 
SYNTHETIC VITREOUS FIBERS 109 

3. HEALTH EFFECTS 

having diameters >5 μm and becomes less pronounced with continued exposure, a “hardening” of the skin 

(ACGIH 2001; Heisel and Hunt 1968; Stam-Westerveld et al. 1994). 

No studies were located regarding the dermal effects of synthetic vitreous fibers in animals after dermal 

exposure. 

Ocular Effects. Occupational exposure to fibrous glass materials, including glass wool insulation and 

fiberglass fabrics, has been associated with acute eye irritation (Longley and Jones 1966; Petersen and 

Sabroe 1991; Stokholm et al. 1982). 

No studies were located regarding the ocular effects of synthetic vitreous fibers in animals after dermal 

exposure. 

No studies were located regarding the following effects in humans or animals after dermal exposure to 

synthetic vitreous fibers: 

3.2.3.3 Immunological and Lymphoreticular Effects 

3.2.3.4 Neurological Effects 

3.2.3.5 Reproductive Effects 

3.2.3.6 Developmental Effects 

3.2.3.7 Cancer 

3.2.4 Other Routes of Exposure 

No studies were located regarding adverse health effects in humans after exposure by other routes to 

synthetic vitreous fibers. 

Intratracheal instillation, interpleural implantation, and intraperitoneal injection studies with synthetic 

vitreous fibers have been performed. Most have been acute-duration studies (single administration 

followed by observation periods up to 2 years). The relevance of these studies to human inhalation 

exposure is unclear because of the high doses and rapid dose rates used, the bypassing of the natural 
 

 

 

 

SYNTHETIC VITREOUS FIBERS 110 

3. HEALTH EFFECTS 

defense systems of the nasal and upper respiratory system, and the overloading or lack (for intraperitoneal 

studies) of pulmonary clearance mechanisms 

Continuous Filament Glass Fibers. Neither intrapleural implantation (Stanton et al. 1972, 1977) nor 

intraperitoneal injection of continuous glass filaments into rats was carcinogenic (Pott et al. 1987). 

Glass Wool. Studies in which glass wool was instilled into the trachea of animals were equivocal; some 

(but not all) demonstrated pulmonary fibrosis (Feron et al. 1985; Mohr et al. 1984; Pickrell et al. 1983; 

Renne et al. 1985; Smith et al. 1987; Wright and Kuschner 1977). Only two of these studies reported 

tumor induction in rats and hamsters (Mohr et al. 1984; Smith et al. 1987). 

Rock Wool. Intratracheal instillation of rock wool did not cause tumor formation in female Syrian 

Golden hamsters (Adachi et al. 1991). 

Slag Wool. No studies were located regarding the adverse health effects of slag wool in animals 

following other routes of exposure. 

Refractory Ceramic Fibers. Intratracheal instillation of a refractory ceramic fiber caused lung cancer in 

male Syrian Golden hamsters, but not in female Osborne-Mendel rats (Smith et al. 1987). Intraperitoneal 

injection of ceramic aluminum silicate fibers in rats and hamsters induced cancer (Davis et al. 1984; 

Smith et al. 1987). Refractory alumina and zirconia fibers injected intraperitoneally did not induce 

fibrosis in rats (Pigott and Tshmael 1981). 

3.3 GENOTOXICITY 

No evidence for genotoxic activity of several synthetic vitreous fibers was found in bacterial mutation 

assays (Chamberlain and Tarmy 1977) or sister chromatid exchange assays in cultured human cells 

(Casey 1983). However, several cytogenetic effects have been observed in other in vitro assays. Notably 

absent are data on genotoxic end points following in vivo exposure of animal or humans to synthetic 

vitreous fibers. Results from short-term in vitro genotoxicity assays are of limited applicability to in vivo 

exposure scenarios because of evidence that long-term residence of synthetic vitreous fibers in the 

principal toxicity target, the lung, can lead to changes (dissolution, breakage into shorter fibers) that can 

decrease biological activities of longer fibers (IARC 2002; also see Section 3.4). 
SYNTHETIC VITREOUS FIBERS 111 

3. HEALTH EFFECTS 

Synthetic vitreous fibers induced: chromosomal aberrations in cultured Chinese hamster cells (Brown et 

al. 1979a, 1979b); morphological transformations in Syrian hamster embryo cells (Hesterberg and Barrett 

1984; Hesterberg et al. 1985; Oshimura et al. 1984) and BALB/c-3T3 cells (Gao et al. 1995; Whong et al. 

1999); micronuclei and multinuclei in Chinese hamster ovary cells (Hart et al. 1992), Chinese hamster 

lung fibroblasts (Ong et al. 1997; Zhong et al. 1997), Syrian hamster epithelial lung cells (Peraud and 

Riebe-Imre 1994), Syrian hamster embryo fibroblasts (Dopp and Schiffmann 1998), and human amniotic 

fluid cells (Dopp and Schiffmann 1998; Dopp et al. 1997); polyploidy in Chinese hamster lung cells 

(Koshi et al. 1991; Sincock et al. 1982); and deoxyribose nucleic acid (DNA) strand breaks and DNADNA interstrand crosslinks in human lung epithelial A549 cells (Wang et al. 1999b). In addition, several 

synthetic vitreous fiber types have been demonstrated to damage isolated DNA (Donaldson et al. 1995c) 

and to hydroxylate 2-deoxyguanosine to 8-hydroxydeoxyguanosine, presumably via hydroxyl radicals 

(Leanderson et al. 1988, 1989). 

There is evidence that fiber dimensions can influence in vitro cytogenetic activities (Hesterberg and 

Barrett 1984; Hesterberg et al. 1985; Ong et al. 1997) and that synthetic vitreous fibers are often less 

active than asbestos fibers (e.g., Donaldson et al. 1995c; Leanderson et al. 1988, 1989; Peraud and RieveImre 1994; Wang et al. 1999b). For example, thin glass fibers (diameters 0.1–0.2 μm, lengths >10 μm) 

were very active in transforming Syrian hamster embryo cells, whereas thick glass fibers (diameter about 

0.8 μm) were much less potent (Hesterberg and Barrett 1984). Milling of the thin glass fibers to reduce 

the length to <1 μm diminished the transforming activity. 

Gene amplification of several proto-oncogenes, H-ras, K-ras, c-myc, and c-fos, has been reported in 

several transformed BALB/C-3T3 cell lines that were induced by a glass fiber (AAA-10 microfiber) 

(Whong et al. 1999). Point mutations, detected by sequencing analysis of DNA from several of the 

transformed cell lines, were also found in the proto-oncogene K-ras, and in the p53 tumor suppressor 

gene (Whong et al. 1999). Induction of c-fos and c-jun proto-oncogenes by crocidolite asbestos was 

demonstrated in cultured hamster tracheal epithelial cells and rat pleural mesothelial cells, but induction 

activities of a glass wool (MMVF10) and a refractory ceramic fiber (RCF1) were much less in this test 

system (Janssen et al. 1994a). 
 

SYNTHETIC VITREOUS FIBERS 112 

3. HEALTH EFFECTS 

3.4 TOXICOKINETICS 

3.4.1 Absorption 

Absorption of synthetic vitreous fibers across the epithelial layers of the respiratory tract, the gastrointestinal tract, and the skin is expected to be low to negligible due to the relatively large physical 

dimensions of these elongated particles (see Chapter 4). However, deposition of inhaled fibers on the 

surface of the epithelial layers of the respiratory tract is an initial process that has been well studied and, 

along with the process of lung clearance, plays an important role in determining toxicity (especially the 

deposition and clearance of fibers in the alveolar region of the respiratory tract). An overview of the 

deposition of inhaled synthetic vitreous fibers in the respiratory tract is presented in the next section 

(Section 3.4.1.1). The deposition of inhaled fibers has been reviewed in more detail in other published 

sources (Dai and Yu 1998; Jones 1993; Lippmann 1990; Morgan 1995; Oberdörster 1994, 2000; Stober 

1972; Stober and McClellan 1997; Timbrell 1965; Yu et al. 1995a). 

3.4.1.1 Inhalation Exposure 

Very limited amounts of inhaled synthetic vitreous fibers are expected to be absorbed in humans or 

animals. Consistent with the expectation of limited, if any, absorption are findings from a study in which 

rats were given single intratracheally-instilled doses (1 mg/rat, equivalent to 3.5x106

 fibers/rat) of a saline 

suspension of radiolabeled (24Na) glass fibers (Morgan et al. 1993). The fibers were produced as a 

continuous filament with an approximate uniform diameter of 2 μm. The fibers in the instilled material 

had a log-normal distribution of lengths, with a median of 16 μm and geometric standard deviation of 1.8. 

Radioactivity measured in urine collected for 24 hours after dose administration accounted for <1% of 

administered radioactivity, and no radioactivity was detected in 24- to 48-hour urine samples. 

Radioactivity in feces collected for 48 hours and in the gastrointestinal tracts and lungs accounted for 

>96% of administered radioactivity in 4/8 rats sacrificed 48 hours after dose administration. The average 

total recovery of administered radioactivity in feces, gastrointestinal tract, and lungs of all eight rats 

was 93%. The average individual percentages of administered radioactivity in the feces, gastrointestinal 

tract, and lungs were 30, 2, and 61%. (In these experiments, radioactivity detected in the gastrointestinal 

tract and feces represents fibers deposited in the respiratory tract, removed by mucous flow to the gastrointestinal tract, and eliminated with the feces—see Sections 3.4.2 and 3.4.4). Morgan et al. (1993) 

reported that, during dose administration, occasional losses of small volumes of the fiber suspension 

occurred (i.e., small volumes remained in the administration apparatus), and that these losses may account 
 

 

1 5 1 2 6 6 DA = 13 . p d L 

SYNTHETIC VITREOUS FIBERS 113 

3. HEALTH EFFECTS 

for the small differences between the calculated administered doses of radioactivity and the total 

radioactivity recovered in the feces, gastrointestinal tract, and lungs. 

There is evidence to suggest that a small amount of inhaled synthetic vitreous fibers may enter the body 

via the lymph nodes. For example, in hamsters exposed for 78 weeks to MMVF10a or MMVF33, 

elevated concentrations of fibers (# fibers/mg dry tissue) were measured in mediastinal tissue containing 

lymph nodes, the diaphragm, and the thoracic wall (Hesterberg et al. 1999). 

The fraction of inhaled synthetic vitreous fibers deposited on the epithelial surface of the respiratory tract 

and the region where deposition occurs are determined by fiber dimensions, fiber density, ventilation 

parameters, and the structure and airway size of the respiratory tract (Dai and Yu 1998; Lippmann 1990; 

Morgan 1995; Yu et al. 1995a). In general, relatively thick inhaled fibers are deposited in the upper 

airways (i.e., the nasopharyngeal region and tracheobronchial regions), and only relatively thin fibers are 

carried to distal regions of the respiratory tract (i.e., the terminal bronchiole and alveolar regions). In the 

large conducting airway regions of the lung and in the nonciliated bronchoalveolar regions, fiber 

deposition is particularly enhanced at branching points (Brody and Roe 1983; Lippmann 1990; Myojo 

1987). 

In published studies of animals exposed by inhalation to different types of fibers, estimates of the fraction 

of inhaled fibers deposited in the lung have ranged from about 1–23% (Okabe et al. 1997). Given the 

complexity of factors influencing apparent lung deposition (e.g., fiber dimensions, exposure duration and 

concentration, ventilation parameters, and airways size and geometry) and the differences in experimental 

conditions and techniques used in these studies, the wide range is not surprising. However, studies that 

restricted periods of exposure to glass wool fibers to 30 minutes (Morgan 1995) or 10 minutes (Okabe et 

al. 1997) to minimize clearance by mucociliary action (see Section 3.4.2) reported values in the upper end 

of the range (15–23%). 

Major mechanisms involved in the deposition of nonelectrostatically charged fibers in the respiratory tract 

include impaction (under high velocity airflows experienced in the larger airways of the respiratory tract), 

gravitational sedimentation (under low velocity airflows), interception, and diffusion. Impaction and 

sedimentation are influenced by the aerodynamic diameter of the particle, whereas interception is 

influenced by the length of the fiber. One formula for aerodynamic diameter (DA) of fibers is: 
 

SYNTHETIC VITREOUS FIBERS 114 

3. HEALTH EFFECTS 

where p=particle density; d=actual diameter; and L=length (Hesterberg and Hart 2001; Stober 1972). For 

glass fibers of uniform particle density, aerodynamic diameters are described by the following formula: 

2 2.  β  DA = 66d     2 + 4 β

where β=length:diameter ratio (Gross 1981). Calculated values of aerodynamic diameters of fibers of a 

uniform density range from about 2.5–4 times that of the actual diameter (Gross 1981; Timbrell 1965). 

More complicated mathematical expressions for aerodynamic diameters of fibers have been derived to 

account for changing orientation of fibers with respect to direction of airflow (Dai and Yu 1998). Fibers 

or particles with aerodynamic diameters >3–5 μm are expected to be predominantly deposited in the 

upper airways and have less probability of traveling to the lower lung than particles or fibers with smaller 

aerodynamic diameters (Morgan et al. 1980; Oberdörster 1994). Based on a review of the literature on 

particle deposition in the human lung, ACGIH (2001) published an algorithm predicting the collection 

efficiency of particles of varying aerodynamic diameters. The algorithm predicts that inhalation exposure 

to particles of uniform aerodynamic diameters of 1, 5, 6, or 10 μm would lead to the following mass 

percentages being deposited in the alveolar or gas-exchange region: 97, 30, 17, or 1%. 

More specific mathematical models to predict the deposition of inhaled fibers in rodents and humans have 

been developed and are discussed in more detail by Yu et al. (1995a) and Dai and Yu (1998), and in 

Section 3.4.5, Physiologically Based Pharmacokinetic/Pharmacodynamic Models. The fraction of inhaled 

fibers that is deposited in the alveolar region is of particular toxicologic interest because fibers deposited 

in this region are more slowly removed than fibers deposited in the nasopharyngeal or tracheobronchial 

regions. Models that predict alveolar deposition fraction for refractory ceramic fibers in rats, hamsters, 

and humans have been used to examine the influence of differences in ventilation parameters, airway size, 

and fiber characteristics on this important parameter (Dai and Yu 1998). The human model predicts that 

increasing workload reduces alveolar deposition fraction and switching from nose-breathing to mouthbreathing increases alveolar deposition fraction. The models predict that alveolar deposition of fibers 

with aerodynamic fibers >3.5 μm and length:diameter ratios >10 is insignificant in rats and hamsters, 

whereas in humans, considerable alveolar deposition occurs with fibers having aerodynamic diameters as 

large as 5–6 μm. For example, for exposure to fibers with 30 μm length, 1.5 μm diameter, and 3.26 μm 

aerodynamic diameter at an air concentration of 1 fiber/cc, calculated alveolar deposition fractions 
SYNTHETIC VITREOUS FIBERS 115 

3. HEALTH EFFECTS 

(expressed as percentage of inhaled fibers) were 0.04% for rats, 0.27% for hamsters, and 6.82% for 

humans (Dai and Yu 1998). 

3.4.1.2 Oral Exposure 

No studies were located examining the possible absorption of ingested synthetic vitreous fibers in humans 

or animals. 

3.4.1.3 Dermal Exposure 

No studies were located examining the possible absorption of synthetic vitreous fibers across the skin of 

humans or animals. 

3.4.2 Distribution 

3.4.2.1 Inhalation Exposure 

Fibers deposited on the epithelial surfaces of the nasal passages and the tracheobronchial tree, which are 

lined with ciliated cells and coated with a mucous layer, are quickly removed by the flow of mucous to 

the pharynx and swallowed into the gastrointestinal tract. This mechanical distribution is generally 

thought to be completed within about 24–48 hours (Jones 1993; Lippmann 1990; Morgan and Holmes 

1980; Oberdörster 1994). A small fraction of fibers deposited in the trachea can be retained within the 

epithelium, as demonstrated in rats intratracheally instilled with suspensions of glass fibers (Morgan 

1995; Morgan et al. 1994a). 

The removal and clearance of fibers deposited on epithelial surfaces of the lower lung, which are lined 

with nonciliated cells without a mucous layer, is comparatively slow. Clearance from this region is 

accomplished by several mechanisms: engulfment by macrophages (phagocytosis) and movement to the 

mucociliary escalator (sometimes referred to as mechanical macrophage-mediated clearance); dissolution 

(either in near neutral [pH 7.4–7.5] extracellular pulmonary fluid or in presumably acidic [pH 4.5–5] 

phagolysosomes of macrophages); and translocation of fibers to the interstitium, the lymphatic 

circulation, and the pleural cavity. These mechanisms influence the biopersistence of inhaled fibers, 

which, along with deposited dose and fiber dimensions, play key roles in determining pulmonary 
SYNTHETIC VITREOUS FIBERS 116 

3. HEALTH EFFECTS 

pathogenesis. Some data illustrating these distribution mechanisms are discussed in this section. For 

more comprehensive reviews, the reader is referred to recent papers by Bernstein et al. (2001a, 2001b), 

Hesterberg and Hart (2000, 2001), and Oberdörster (2000) and other earlier papers (Bellmann et al. 

1994a, 1994b; Bernstein et al. 1995; Muhle and Bellmann 1995, 1997; Musselman et al. 1994; 

Oberdörster 1994). 

Macrophages are motile cells found in the lung interstitium, on the surface of epithelial cells lining the 

alveoli, and on the surface of ciliated epithelial cells (Carpenter and Wilson 1999; Valberg and Blanchard 

1991). They are capable of engulfing foreign materials in the conducting airways, the alveoli, and the 

interstitium and moving onto the mucociliary escalator. Macrophages facilitate a major clearance 

mechanism for the lower respiratory tract. Macrophage engulfment, however, is limited to fibers with 

lengths less than the diameter of the macrophage. Alveolar macrophage diameters range from about 10– 

13 μm in rats and 14–21 μm in humans (Hesterberg and Hart 2001; Oberdörster 2000). Fibers longer than 

about 20 μm are not expected to be cleared by macrophages unless they undergo transverse breakage 

(Eastes et al. 2000; Hesterberg and Hart 2001; Hesterberg et al. 1998a; Oberdörster 2000). 

Results from early studies of lung clearance of intratracheally-instilled glass wool fibers of varying 

lengths in rats provided evidence of the inability of macrophages to engulf and clear long fibers, the 

dissolution and transverse breakage of synthetic vitreous fibers in the lung, and the limited degree to 

which fibers may be translocated to the lymph nodes (Morgan et al. 1982). In these studies, rats were 

given single intratracheal instillations of sized glass wool fibers with median diameters of about 1.5 μm 

and median lengths of 5, 10, 30, or 60 μm. 

Long Fibers are Poorly Cleared by Macrophages. For the 5- and 10-μm length fibers, the number of 

fibers remaining in lungs declined smoothly with time after administration (Morgan et al. 1982). At 

1 year, 90 and 80% of the injected 5- and 10-μm length fibers, respectively, had been cleared. In contrast, 

the number of fibers in lungs of rats exposed to 30- or 60-μm length fibers did not decline over a 9-month 

period after administration, indicating no discernible clearance. The fibers recovered at 9 and 18 months 

from the lungs of rats exposed to 60-μm length fibers showed evidence of transverse breakage of the 

fibers. The respective median lengths of recovered fibers at these times were 40 and 25 μm. The number 

of fibers in lungs at 9 months was 20–30% greater than the number in lungs of similarly exposed rats at 

2 days after administration. (Fibers were not counted at 18 months because the 9-month results indicated 
SYNTHETIC VITREOUS FIBERS 117 

3. HEALTH EFFECTS 

that transverse breakage would influence recovered fiber number more than any possible clearance 

mechanism). 

Glass Fibers Dissolve at pH 7.4–7.5. Fibers recovered at 18 months also showed decreased diameters 

indicating dissolution within the lung (Morgan et al. 1982). Median diameters of recovered fibers at 

18 months in the groups exposed to 5-, 10-, 30-, and 60-μm length fibers were decreased by 12, 28, >50, 

and >50%, respectively, of the original 1.5-μm diameters, indicating faster dissolution of longer fibers 

than shorter fibers. This result is consistent with the faster in vitro dissolution of glass fibers at pH 7.4– 

7.5 (the pH of extracellular fluid in the lung) than at acidic pHs (4.5–5) found within the phagolysosomes 

of macrophages (Oberdörster 2000). However, not all types of synthetic vitreous fibers show faster in 

vitro dissolution at pH 7.4–7.5 than at acidic pHs. For example, MMVF34, a stone wool, has been shown 

to be very biosoluble in the rat lung, poorly soluble in vitro at pH 7.4–7.5, and soluble in vitro at pH 4.5 

(Hesterberg and Hart 2001). 

Limited Translocation of Fibers to the Lymphatic Circulation may Occur. One year after 

administration, the fibers detected in hilar lymph nodes of rats exposed to 5-μm long glass fibers 

accounted for only 4% of the total lung fiber number (Morgan et al. 1982). The hilar lymph nodes 

contained smaller proportions of recovered fibers in rats exposed to the 10- and 30-μm length fibers. At 

the same time period, no fibers were detected in the hilar lymph nodes of rats exposed to 60-μm length 

fibers. The results indicate that only limited numbers of glass fibers were translocated to the lymph nodes 

under these experimental conditions. 

Other studies with rats, hamsters, or guinea pigs indicate that considerable translocation of inhaled fibers 

to lymph nodes and the pleural cavity can occur under conditions that overload the mucociliary clearance 

mechanism (Lee et al. 1981a). In these studies, animals were exposed by inhalation to high 

concentrations (2,900, 13,500, or 41,800 fibers/cc) of potassium octatitanate fibers (average length of 

6.7 μm and diameter of 0.2 μm) for 3 months. Numerous dust-laden macrophages were observed in 

tracheobronchial and mediastinal lymph nodes and in mediastinal adipose tissue adjacent to the lymph 

nodes when the animals were sacrificed 15 months after exposure ceased. Dust-laden macrophages also 

accumulated in the pleural cavity. Exposed animals showed fibrosis in the respiratory bronchiolar region 

and hyperplasia of the pleural mesothelium that increased in severity with exposure concentration (Lee et 

al. 1981a). 
SYNTHETIC VITREOUS FIBERS 118 

3. HEALTH EFFECTS 

Evidence of rapid translocation of small numbers of short and thin fibers to pleural tissue has been 

observed in rats and hamsters after inhalation exposure to a refractory ceramic fiber, RCF1 (Everitt et al. 

1997; Gelzleichter et al. 1996a, 1996c, 1999). In an acute exposure study, rats were exposed (nose-only) 

to concentrations of 2,645 WHO respirable fibers/cc (length:diameter ≥3:1, length >5 μm, diameter 

<3 μm) 6 hours/day for 5 days (Gelzleichter et al. 1996a, 1996c). The aerosol concentration of total 

fibers (length:diameter ratio ≥3:1) was 6,206 fibers/cc. Rats were sacrificed immediately after and 

32 days after exposure. Fiber concentrations and dimensions in lung and pleural tissue samples were 

measured using scanning electron microscopy. At both sampling dates, lung fiber concentrations were 

about 1,000-fold greater than pleural fiber concentrations, indicating that relatively small numbers of 

fibers were translocated from the lung to the pleura. Average pleural fiber concentrations declined from 

25,000 fibers/pleura at day 5 to 15,700 fibers/pleura at day 32, indicating some clearance of pleural fibers 

after exposure ceased. All fibers found in pleural tissues had lengths <5 μm and diameters <0.35 μm. 

Fibers detected in the pleural samples had geometric mean lengths of 1.4 and 1.5 μm, and geometric mean 

diameters of 0.87 and 0.10 μm, at days 5 and 32, respectively. In contrast, geometric mean lengths and 

diameters of fibers detected in lung tissue were notably larger than pleural fibers and were similar to the 

values for the exposure aerosol (geometric mean length, 4.54 μm [range: 0.7–111 μm] and geometric 

mean diameter, 0.56 μm). In subsequent studies in which rats or hamsters were exposed to about 

300 WHO fibers/cc of RCF1, 4 hours/day, 5 days/week for up to 12 weeks, fibers detected in pleural 

tissue (sampled at 4 or 12 weeks or 12 weeks after exposure ceased) also displayed shorter mean lengths 

and thinner mean diameters than the fibers in the exposure aerosol (Everitt et al. 1997; Gelzleichter et al. 

1999). In lung tissues in both species at all time points, fibers longer than 5 μm accounted for 

approximately 67% of detected fibers, whereas in pleural tissue, fibers longer than 5 μm accounted for 

12% in hamsters and 4% in rats (Gelzleichter et al. 1999). 

The biopersistence of fibers in lungs has been examined in several studies of rodents following acute 

(5-day) inhalation exposures to a number of glass wools, continuous filament glass, rock and slag wools, 

and a refractory ceramic fiber, as well as amosite or crocidolite asbestos (Bernstein et al. 1996; Eastes and 

Hadley 1995; Hesterberg et al. 1996, 1998a, 1998b). Lung tissues were sampled at several times after 

exposure from 1 hour up to 1 year, and concentrations and dimensions of fibers in the tissues were 

measured using scanning electron microscopy. These studies focused on the clearance of fibers with 

lengths >20 μm, which is thought to be mediated mainly by dissolution and subsequent transverse 

breakage, rather than direct mechanical macrophage-mediated clearance. One- and two-compartment 

first-order exponential models were fit to lung concentration data for fibers with lengths >20 μm. For 
 

SYNTHETIC VITREOUS FIBERS 119 

3. HEALTH EFFECTS 

most fiber types, the two-compartment model provided a better fit than the one-compartment model. 

From the two models, two measures of lung clearance were used to compare the biopersistence of fiber 

types—a weighted clearance half-time that incorporated the half-times from the slow and fast 

compartment of the two-compartment model (WT1/2: Bernstein et al. 1996) or the days required for 

clearance of 90% of the fibers with lengths >20 μm that were present in the lung 1 day after cessation of 

exposure. For fiber types for which a two-compartment model did not provide an improved fit over a 

one-compartment model, clearance half-time (T1/2) was compared with WT1/2 for the other fibers. 

Using either measure of lung biopersistence (WT1/2 or T-90 for fibers with lengths >20), synthetic 

vitreous fibers showed a considerable range of values, but all were markedly less biopersistent than 

amosite and crocidolite asbestos (Table 3-2). Amosite and crocidolite asbestos showed high WT1/2 values 

(418 and 817 days, respectively), several durable synthetic vitreous fibers showed moderately high WT1/2 

values between 37 and 91 days, and several glass wools, a slag wool, and newly developed rock wools 

showed WT1/2 values below 13 days (Table 3-2). 

The dissolution of a variety of synthetic vitreous fibers has been extensively studied in vitro in simulated 

physiological fluids (Bernstein et al. 1996; Christensen et al. 1994; Eastes and Hadley 1995; Knudsen et 

al. 1996; Mattson 1994; Potter and Mattson 1991; Scholze and Conradt 1987). These studies are often 

conducted at pH 7.4 to simulate acellular dissolution and pH 4.5 to simulate dissolution in the acidic 

phagolysosomes of macrophages. The following equation is fit to in vitro data for changing fiber 

diameter (D) with time (t) to provide estimates of Kdis, the dissolution rate coefficient, for different fiber 

types: 

D t() = D0 − 2 K dist / ρ

where ρ is the density of the fiber, and Kdis is usually in units of ng/cm2

-hour. A larger coefficient 

indicates faster dissolution. Amphibole asbestos fibers, such as crocidolite or amosite, essentially do not 

dissolve at pH 7.4 and have Kdis values <1 (Table 3-2). In contrast, synthetic vitreous fibers dissolve, but 

show variance among fiber types in rates of dissolution. Kdis values for synthetic vitreous fibers in 

Table 3-2 range from 3 to >500 ng/cm2

-hour. In vitro dissolution rates are correlated with rates of lung 

clearance, but several exceptions indicate that dissolution at pH 7.4 is not the only determinant of lung 

biopersistence (Table 3-2). For example, MMVF34 (HT rock wool) has a moderately low in vitro pH 

7.4 Kdis (59 ng/cm2

-hour), but displays very fast lung clearance (WT1/2=6 days). In contrast, MMVF10 

(insulation glass wool) has a high pH 7.4 Kdis (300 ng/cm2

-hour), but displays slow lung clearance 
SYNTHETIC VITREOUS FIBERS 120 

3. HEALTH EFFECTS 

Table 3-2. Lung Clearance of Fibers with Lengths >20 μm in F344 Male Rats 

Following Nose-only Inhalation Exposure (6 Hours/Day for 5 Days) to 

19 Different Synthetic Vitreous Fibers or Two Types of Asbestos 

Fiber Weighted half-time 90% clearance In vitro Kdis, 

name Type (WT1/2, days) (T-90, days) pH 7.4a 

Amosite Asbestos 418 2,095 <1 

Crocidolite Asbestos 817b

 2,270 <1 

MMVF32 Special application continuous filament 79 371 9 

glass 

MMVF21 Rock (stone) wool 67 (91)c

 264 (206)c 21 

RCF1a Refractory ceramic fiber 55 227 3 

MMVF33 Durable special applications glass 49 240 12 

L Traditional rock wool 45 186 20 

MMVF10 Insulation glass wool 37b

 123 300 

H New rock wool 13 49 270 

MMVF11 Insulation glass wool 9 (13)c

 38 (40)c 100 

MMVF22 Slag wool 9 37 400 

J Experimental 10 18 170 

9b F New rock wool 28 160 

MMVF34 New rock wool (HT fiber, soluble in 6 19 59 

acid) 

6b O Rock wool 20 >500 

6b P Glass wool 19 >500 

5b M Glass wool 18 >500 

5b G New rock wool 18 210 

A New glass wool 4 9 250 

C New glass wool 4 14 >500 

B B-01/09 (glass wool) 2 8 >500 

a

Kdis is the empirically derived coefficient (in ng/cm2-hour) for in vitro dissolution in a flowing physiological saline 

solution at pH 7.4. A larger coefficient indicates faster dissolution. 

b

Values are half-times (T1/2) from a one-compartment model; the two-compartment model did not provide an 

improved fit. 

c

Values in parentheses are from a second experiment. 

Source: Hesterberg et al. 1998a 
 

 

SYNTHETIC VITREOUS FIBERS 121 

3. HEALTH EFFECTS 

(WT1/2=37 days) compared with other synthetic vitreous fibers. Short-term in vivo lung clearance tests 

and in vitro dissolution tests have been proposed as preliminary screening tools to predict lung 

biopersistence and subsequent toxicity of untested fibers (Davis et al. 1996; Eastes et al. 2000; Zoitos et 

al. 1997). 

Results from short-term in vivo lung clearance tests reflect the accumulation and biopersistence of fibers 

in the lungs of animals exposed for chronic durations. For example, lung elimination half-times for fibers 

with lengths >20 μm after 5 days of inhalation exposure of rats to comparable concentrations of rock 

wools MMVF21 or MMVF 34 (HT rock wool) were 92 days and 5 days, respectively, reflecting 

moderate and low biopersistence of the two rock wools (Kamstrup et al. 1998). This difference in 

biopersistence was reflected in lung concentrations in rats exposed (nose-only, 6 hours/day, 5 days/week) 

to comparable concentrations of the two rock wools for up to 18 months. Rats exposed to 

MMVF34 showed lung concentrations for fibers with lengths >20 μm of 8, 11, 10, and 11 fibers per mg 

dry lung x103

 at respective sampling times of 3, 6, 12, and 18 months. These findings are consistent with 

early attainment of a balance between continued exposure and fast dissolution (i.e., low biopersistence) of 

this fiber. In contrast, concentrations in rats exposed to the moderately biopersistent fiber, MMVF21, 

were higher and showed evidence of accumulation with time at the same sampling times: 18, 23, 55, and 

62 fibers per mg lung x103

. 

3.4.2.2 Oral Exposure 

No studies were located examining distribution of ingested synthetic vitreous fibers in humans or animals. 

3.4.2.3 Dermal Exposure 

No studies were located examining distribution of dermally applied synthetic vitreous fibers in humans or 

animals. 

3.4.2.4 Other Routes of Exposure 

The clearance kinetics of a variety of synthetic vitreous fibers from the respiratory tract following 

intratracheal instillations of suspensions of fibers has been studied in several animal species including 
 

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rats, hamsters, and sheep (Bellmann et al. 1994a, 1994b, 1995; Dufresne et al. 1999; Eastes et al. 1995; 

Morgan et al. 1982, 1994a; Morris et al. 1995; Searl et al. 1999). Intratracheal instillation offers the 

advantage of being less expensive than inhalation experiments, and results from these studies are 

supportive of results from clearance studies following inhalation. For example, the intratracheal 

instillation study by Morgan et al. (1982) discussed in the previous section provided evidence of the 

inability of macrophages to engulf and clear long fibers, the dissolution and transverse breakage of 

synthetic vitreous fibers in the lung, and the limited degree to which fibers may be translocated to the 

lymph nodes. However, this mode of administration has a few disadvantages, relative to inhalation 

exposure, including the increased potential to form clumps of fibers and the induction of inflammatory 

responses to high bolus doses (Oberdörster 2000). Because clumping and inflammation may influence 

fiber dissolution and clearance, the results from clearance studies following intratracheal instillations are 

not discussed further in this section. 

3.4.3 Metabolism 

3.4.3.1 Inhalation Exposure 

Synthetic vitreous fibers are not metabolized via typical enzyme-mediated processes, but undergo 

dissolution at varying rates depending on fiber composition, manufacturing processes under which the 

fibers were formed, and physical and chemical conditions in which the fiber may exist (Hesterberg and 

Hart 2001; Zoitos et al. 1997). In general, the dissolution of vitreous fibers in physiological fluids is 

thought to occur via reactions in which a water molecule (or some part thereof) replaces a cation in the 

matrix of the fiber (Eastes et al. 2000). In the simplest model for dissolution, all components in the 

matrix are assumed to dissolve at approximately the same rate. This model is used in the traditional 

determinations of Kdis, the in vitro dissolution rate coefficient, for various fibers. However, for many 

synthetic vitreous fibers, certain components dissolve more rapidly than others. Vitreous fibers with high 

alumina and silica contents favor a uniform rate of dissolution of all components, whereas fibers with a 

lower proportion of alumina and silica (<63 mole%) show nonuniform dissolution rates in which oxides 

of calcium, magnesium, and potassium dissolve quickly, leaving a weakened silica matrix (Hesterberg 

and Hart 2001). At points where the matrix is weakened, applied physical stress can lead to transverse 

breakage of the fiber. More complicated models to predict fiber dissolution without assuming uniform 

dissolution rates for all components are under development (Eastes et al. 2000; Hesterberg and Hart 

2001). 
SYNTHETIC VITREOUS FIBERS 123 

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Synthetic vitreous fibers have amorphous molecular structures that do not have planes of cleavage such as 

those in the crystal structure of chrysotile asbestos. The longitudinal cleavage of asbestos fibers can form 

thinner fibers that may more readily move into the interstitium or the pleura cavity (Agency for Toxic 

Substances and Disease Registry 2001). This property is not expected with synthetic vitreous fibers and 

may contribute to the difference in potency between asbestos and synthetic vitreous fibers. In addition, 

asbestos fibers, especially amphibole fibers, undergo very little, if any, dissolution in in vitro pH 7.4 tests 

(see Table 3-2). The relatively high persistence of long amphibole asbestos fibers in lungs is 

demonstrated by long clearance half-times of amphibole asbestos in rats (as shown in Table 3-2). 

Chrysotile asbestos, the least persistent asbestos type, is also expected to be more persistent in lungs than 

most synthetic vitreous fibers. For example, in rats following 10-day inhalation exposure to similar 

concentrations of chrysotile or a special purpose Code 100/475 glass fiber, the lung clearance half-time 

for long (>15 μm) chrysotile fibers was 46.2 weeks, whereas the half-time for long Code 100/475 glass 

fibers was 6.6 weeks (Searl 1997). 

3.4.3.2 Oral Exposure 

No studies were located regarding compositional or structural changes in synthetic vitreous fibers in the 

gastrointestinal tract. 

3.4.3.3 Dermal Exposure 

No studies were located regarding compositional or structural changes in synthetic vitreous fiber after 

dermal exposure. 

3.4.4 Elimination and Excretion 

3.4.4.1 Inhalation Exposure 

As discussed in Section 3.4.2.1, the principal pathways by which synthetic vitreous fibers are removed 

from the respiratory tract involve (1) mechanical mucociliary translocation to the pharynx, swallowing 

into the gastrointestinal tract, and elimination in the feces, (2) dissolution, and (3) transverse breakage of 

long fibers into shorter fibers. Mechanical translocation is mediated directly with fibers deposited on the 

surface of the ciliated epithelium of the respiratory tract and via macrophages when fibers are deposited in 
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the nonciliated epithelial region in the lower respiratory tract. After fibers or fiber-laden macrophages are 

on the mucociliary escalator, mechanical translocation is thought to be complete within about 24– 

48 hours (Jones 1993; Lippmann 1990; Morgan and Holmes 1980; Oberdörster 1994). Clearance of 

synthetic vitreous fibers from the lower airways is slower but shows variance with fiber types and 

dimensions. For example, clearance half-times for fibers longer than 20 μm in the lungs of rats have been 

reported to range from 2 to 79 days for 19 different synthetic vitreous fibers (Hesterberg et al. 1998a; see 

Table 3-2). For asbestos fibers in rats, more rapid clearance of shorter (<5 μm) fibers than of longer 

(>10 or 20 μm) fibers has been observed. This is explained as a result of the relative difficulty with 

which longer fibers are engulfed by macrophages. In contrast, many synthetic vitreous fibers show a 

more rapid clearance rate for long fibers compared with short fibers. This difference is consistent with 

the inability of macrophages to engulf long fibers, the relatively rapid dissolution of many synthetic 

vitreous fibers in the near-neutral pH solution of the intracellular spaces in the lung, and the subsequent 

transverse breakage of long vitreous fibers into shorter fibers. For example, lung clearance half-times in 

rats for long (>20 μm) fibers were 44, 6, and 986 days for MMVF10, MMVF11, and crodidolite asbestos, 

respectively; for short (<5 μm) fibers, the respective half-times were 111, 46, and 44 days (Hesterberg et 

al. 1996). 

3.4.4.2 Oral Exposure 

No studies were located regarding excretion of synthetic vitreous fibers after oral exposure. Most, if not 

all, synthetic vitreous fibers that are ingested are expected to be excreted in the feces. Fecal elimination 

of a single oral dose of asbestos fibers has been demonstrated to be essentially complete within 48 hours 

(Gross and Stanton 1974). 

3.4.4.3 Dermal Exposure 

No studies were located regarding excretion of synthetic vitreous fibers following dermal exposure, but it 

is generally considered that dermal exposure does not result in absorption of these fibers. 
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3.4.4.4 Other Routes of Exposure 

As with inhaled fibers, intratracheally-instilled synthetic vitreous fibers are cleared by mucociliary 

translocation, dissolution, and transverse breakage (Bellmann et al. 1994a, 1994b, 1995; Dufresne et al. 

1999; Eastes et al. 1995; Morgan et al. 1982, 1994a; Morris et al. 1995; Searl et al. 1999). Fibers 

swallowed into the gastrointestinal are efficiently excreted in the feces. 

3.4.5 Physiologically Based Pharmacokinetic (PBPK)/Pharmacodynamic (PD) Models 

Physiologically based pharmacokinetic (PBPK) models use mathematical descriptions of the uptake and 

disposition of chemical substances to quantitatively describe the relationships among critical biological 

processes (Krishnan et al. 1994). PBPK models are also called biologically based tissue dosimetry 

models. PBPK models are increasingly used in risk assessments, primarily to predict the concentration of 

potentially toxic moieties of a chemical that will be delivered to any given target tissue following various 

combinations of route, dose level, and test species (Clewell and Andersen 1985). Physiologically based 

pharmacodynamic (PBPD) models use mathematical descriptions of the dose-response function to 

quantitatively describe the relationship between target tissue dose and toxic end points. 

PBPK/PD models refine our understanding of complex quantitative dose behaviors by helping to 

delineate and characterize the relationships between: (1) the external/exposure concentration and target 

tissue dose of the toxic moiety, and (2) the target tissue dose and observed responses (Andersen et al. 

1987; Andersen and Krishnan 1994). These models are biologically and mechanistically based and can 

be used to extrapolate the pharmacokinetic behavior of chemical substances from high to low dose, from 

route to route, between species, and between subpopulations within a species. The biological basis of 

PBPK models results in more meaningful extrapolations than those generated with the more conventional 

use of uncertainty factors. 

The PBPK model for a chemical substance is developed in four interconnected steps: (1) model 

representation, (2) model parametrization, (3) model simulation, and (4) model validation (Krishnan and 

Andersen 1994). In the early 1990s, validated PBPK models were developed for a number of 

toxicologically important chemical substances, both volatile and nonvolatile (Krishnan and Andersen 

1994; Leung 1993). PBPK models for a particular substance require estimates of the chemical substancespecific physicochemical parameters, and species-specific physiological and biological parameters. The 
SYNTHETIC VITREOUS FIBERS 126 

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numerical estimates of these model parameters are incorporated within a set of differential and algebraic 

equations that describe the pharmacokinetic processes. Solving these differential and algebraic equations 

provides the predictions of tissue dose. Computers then provide process simulations based on these 

solutions. 

The structure and mathematical expressions used in PBPK models significantly simplify the true 

complexities of biological systems. If the uptake and disposition of the chemical substance(s) are 

adequately described, however, this simplification is desirable because data are often unavailable for 

many biological processes. A simplified scheme reduces the magnitude of cumulative uncertainty. The 

adequacy of the model is, therefore, of great importance, and model validation is essential to the use of 

PBPK models in risk assessment. 

PBPK models improve the pharmacokinetic extrapolations used in risk assessments that identify the 

maximal (i.e., the safe) levels for human exposure to chemical substances (Andersen and Krishnan 1994). 

PBPK models provide a scientifically sound means to predict the target tissue dose of chemicals in 

humans who are exposed to environmental levels (for example, levels that might occur at hazardous waste 

sites) based on the results of studies where doses were higher or were administered in different species. 

PBPK models for insoluble or slowly soluble inhaled materials, such as synthetic vitreous fibers, focus on 

the retention of the inhaled materials in the alveolar region of the lung (Stober and McClellan 1997). The 

models recognize that alveolar retention (the net result of the deposition and clearance processes in the 

alveolar region) is also dependent on deposition and clearance of particles in the upstream regions of the 

respiratory tract. The models divide the respiratory system into a number of connected compartments 

(most often into the nasopharyngeal, tracheobronchial, and alveolar regions) with each compartment 

having a distinct set of deposition and clearance parameters. As reviewed below, alveolar retention 

models for refractory ceramic fibers have been developed for rats, hamsters, and humans; the rat model 

has recently been extended to other synthetic vitreous fibers such as glass, rock, and slag wools (Yu et al. 

1994, 1995b, 1996, 1998a, 1998b). 

Models for alveolar retention of refractory ceramic fibers in rats and hamsters have been developed based 

on: (1) theoretical and empirical understanding of deposition processes (e.g., sedimentation and 

impaction) in various regions of the respiratory tract as they are influenced by particle dimensions, 

airflow characteristics, and airway geometry; (2) understanding that clearance processes include direct 
 

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mechanical mucociliary clearance, macrophage-mediated mucociliary clearance, dissolution, and 

transverse breakage of long fibers into shorter fibers; and (3) data for lung concentrations and size 

distributions of fibers in animals exposed chronically to accurately measured inhaled concentrations of 

refractory ceramic fiber (RCF1) aerosols (Yu et al. 1994, 1995b, 1996). The rat model for refractory 

ceramic fibers was also extended to a more general model to apply to other synthetic vitreous fiber 

including glass wools and rock wools (Yu et al. 1998a, 1998b). 

The most recent of the retention models developed by Yu and colleagues include mathematical 

descriptions of alveolar deposition rates with the following explanatory variables: tidal volume, breathing 

frequency, air concentrations of fibers of specific lengths and diameters, and alveolar deposition fraction 

of fibers with specific diameter and length. The deposition models account for the dependence of the 

fraction of inhaled fibers depositing in the alveolar region not only on the deposition efficiency of the 

alveolar region itself (i.e., the amount deposited divided by the amount entered), but also on deposition 

efficiencies in the nasopharyngeal and tracheobronchial regions. The clearance models describe removal 

of fibers from lungs by three simultaneous processes: alveolar macrophage-mediated clearance (as a 

function of fiber length and alveolar macrophage volume); dissolution (decrease in fiber diameter with 

time at a constant rate); and transverse breakage of long fibers into shorter fibers (Yu et al. 1996, 1997, 

1998a, 1998b). Macrophage-mediated clearance in the model is also a function of lung burden, the total 

accumulated fiber and particle volume in the lung; the rate of clearance slows at high lung burdens. 

Model simulations of lung concentrations of fibers of various length classes (lengths <5, 5–10, 10–20, 

and >20 μm) showed good agreement with empirical lung concentrations in rats exposed (nose-only, 

6 hours/day, 5 days/week) for up to 104 weeks to RCF1 concentrations of 36, 91, 162, and 234 total 

fibers/cc (Yu et al. 1996). Good agreement was also found between model simulations and empirical 

lung concentrations in rats at various postexposure periods following exposure (nose-only, 6 hours/day 

for 5 days) to each of four types of synthetic vitreous fibers (two glass wools—MMVF10, MMVF11; one 

rock wool—MMVF21; or one slag wool—MMVF22) at gravimetric concentrations of 30 mg/m3

 (Yu et 

al. 1998a). Model simulations were also compared with lung concentration data for rats exposed by 

inhalation for up to 104 weeks to several concentrations of the same synthetic vitreous fibers (MMVF10, 

MMVF11, MMVF21, or MMVF22) (Yu et al. 1998b). The model simulations were reported to “compare 

quite well” with the data, but a statistical analysis of fit was not conducted. 
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A deposition and clearance model for refractory ceramic fibers in humans was developed from the rat 

model based on anatomical and physiological differences between rats and humans (Yu et al. 1995a, 

1997). Some of the differences used in developing the human model are described in Table 3-3. 

Appropriate data to examine the accuracy of the human model are not available (i.e., lung fiber 

concentrations from autopsied lungs of exposed subjects and accurate information regarding timeweighted average air concentrations to which the subjects were exposed and durations of exposure). The 

model was used, however, to predict human lung concentrations following 15–20 years of occupational 

exposure to various air concentrations of refractory ceramic fibers. These were compared with lung 

concentration data for three workers who worked in a refractory ceramic fiber manufacturing plant for 

13–17 years (Yu et al. 1997). The comparison suggested that one subject may have been exposed to an 

average air concentration of 0.25 fibers/cc and that the other subjects may have been exposed to 0.6– 

0.7 fibers/cc. These concentrations are within the range of air concentrations measured for some 

refractory ceramic fiber manufacturing plants (Yu et al. 1997). 

For refractory ceramic fiber size ranges and concentrations encountered in workplaces, the deposition 

models predicted that: (1) the average alveolar deposition fraction in humans is 8.4% for nose-breathing 

and 15.9% for mouth-breathing; (2) the average alveolar deposition fraction in rats and hamsters are 

3.7 and 5.7%, respectively; (3) humans have 1–2.5 times less deposited fiber per unit lung surface area 

than rats and hamsters; and (4) the geometric mean size dimensions (diameter and length) of fibers 

deposited in the lungs of rats and hamsters are smaller than those of fibers deposited in human lungs (Yu 

et al. 1995a). 

One impetus to develop rat, hamster, and human alveolar retention models for synthetic vitreous fibers is 

to use the models to facilitate animal-to-human extrapolations of dose-response relationships for adverse 

effects in rodents exposed by inhalation to synthetic vitreous fibers (see Section 3.5.3, Animal-to-Human 

Extrapolations and Appendix A). Several quantitative human cancer risk estimates have been prepared 

using the data from the RCF1 2-year rat bioassay and the lung deposition and clearance models developed 

by C.P. Yu and colleagues (Maxim et al. 2003b; Moolgavkar et al. 1999, 2000; Turim and Brown 2003; 

Yu and Oberdörster 2000). 
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Table 3-3. Comparative Human and Rat Anatomical and Physiological 

Parameters Relevant to Alveolar Retention of 

Refractory Ceramic Fibers 

Parameter Human Rat 

Body weight (kg) 70 0.3 

Lung weight (g) 1,000 1.48 

Airway volume (cm3

) 3,200 6.5 

Airway surface area (cm2

) 627,000 5,500 

Number of alveolar macrophages 7x109

 2.6x107 

Alveolar macrophage volume (μm3

 per lung) 2,500 1,000 

Total alveolar macrophage volume (mm3

) 17,500 26 

Tidal volume (cm3

) 500 2.74 

Breathing frequency (minute-1) 14 98 

Minute ventilation (cm3

/minute) 7,000 268 

Life span (years) 70 2 

Source: Yu et al. 1997 
 

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3.5 MECHANISMS OF ACTION 

The mechanisms by which inhaled fibers and particles, including synthetic vitreous fibers, induce adverse 

effects on the lung and pleural membrane are incompletely understood, but extensive research over the 

past few decades with asbestos fibers, silica, and synthetic vitreous fibers of various types has led to a 

complex working hypothesis that includes pharmacokinetic mechanisms influencing the dose of fibers to 

the lung and toxicity mechanisms involving the responses of lung cells and tissues to retained fibers. 

Evidence has accumulated that these mechanisms are influenced to varying degrees by fiber dimensions, 

dose to the lung, and fiber durability; surface area and chemical composition not related to durability may 

also play roles in the mechanisms. This section provides a brief overview of mechanisms involved in 

fiber-induced effects on the lung (inflammation, cytotoxicity, genotoxicity, cell proliferation, fibrosis, and 

lung tumors) and the pleural membrane (pleural plaques, pleural thickening and pleural mesothelioma). 

More detailed and comprehensive information on this area of research can be found in reviews by Churg 

et al. (2000), Driscoll (1996), Hart et al. (1994), Hesterberg and Hart (2001), Hesterberg et al. (1993c), 

Kane (1996), and Mossman and Churg (1998). 

3.5.1 Pharmacokinetic Mechanisms 

The amount of fibers deposited in the alveolar region of the lung is a key determinant of the potential 

development of adverse effects in the interstitium of the lung and in the pleural membrane. The 

aerodynamic diameter of fibers, along with ventilation parameters and geometry and size of airways, 

strongly influence alveolar deposition (Dai and Yu 1998; Oberdörster 2000). Fibers with aerodynamic 

diameters >3–4 μm are mostly excluded from the alveolar region due to deposition in upstream regions of 

the respiratory tract. The fraction of inhaled fibers deposited in alveoli decreases to zero with 

aerodynamic diameters of about 5 μm in rats and 10 μm in humans (Dai and Yu 1998). 

The mechanisms whereby fibers deposited in the alveoli move to the interstitium, the pleural membrane, 

or the lymphatic system are unknown, although it is believed that movement into these regions is 

enhanced when rates of dissolution and macrophage-mediated clearance are overwhelmed by intakes at 

high exposure concentrations (Gross and Stanton 1973; Oberdörster 2000). Using electron microscopy, 

recent experiments have detected predominately short (<5 μm) and thin (<0.35 μm) fibers in pleural 

tissues after acute or intermediate inhalation exposure of rats and hamsters to a refractory ceramic fiber, 
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3. HEALTH EFFECTS 

RCF1 (Everitt et al. 1997; Gelzleichter et al. 1996a, 1996b, 1999). These findings suggest that rapid fiber 

movement into pleural tissues occurs and has size limitations. Whether the movement is principally 

passive through intracellular spaces or mediated by the movement of inflammatory cells is unknown. The 

detection of fibers in the pleural tissues in the intermediate-duration studies was accompanied by 

inflammation and cell proliferative changes in pleural tissue. Hamsters showed more severe pleural 

changes than rats, but this was not correlated with a greater total number of fibers in hamster pleural 

tissues (Everitt et al. 1997). However, more extensive subsequent examinations of fiber size distributions 

in pleural tissues from rats and hamsters following intermediate-duration exposure to RCF1 found that 

fibers longer than 5 μm accounted for 12 and 4% of the fiber burden in hamsters and rats, respectively 

(Gelzleichter et al. 1999). The pleural surface density of these “long” fibers in hamsters (150 fibers per 

cm2

) was about 2–3 times that in the rat, whereas the pleural burden of short (<5 μm) fibers in the rats 

was about 1.5–2 times that in the hamster. The differences between hamsters and rats in intermediateduration pleural cell proliferative changes may be due, in part, to the differences in retained “long” fiber 

surface density, but contributions from other mechanisms, such as release of reactive oxygen species, 

cytokines, or growth factors from alveolar macrophages or other cells are also plausible (Adamson et al. 

1994). 

The dose of fibers that remains in the lower lung is a net result of the amount of fibers deposited and the 

amount of deposited fibers removed by macrophage-mediated clearance via the mucociliary escalator, 

and by the combined actions of dissolution and transverse breakage of long fibers into shorter fibers. 

Whereas fiber aerodynamic diameter is a critical factor for deposition, fiber length is a critical factor for 

macrophage engulfment. Fibers longer than 15–20 μm are expected to be too long for human 

macrophages to completely engulf and transport out of the lung. Thus, clearance of long fibers from the 

lower lung cannot occur until the fibers either dissolve or break into shorter fibers that can be removed by 

macrophages (Eastes et al. 2000; Hesterberg and Hart 2001; Hesterberg 1998a; Oberdörster 2000). 

Dissolution of fibers is influenced by their chemical composition and structure. As discussed in 

Section 3.4, synthetic vitreous fibers of various types show a range of in vitro dissolution rates (that are 

correlated with in vivo lung clearance half-times in rats), but all synthetic vitreous fibers tested to date are 

less biopersistent than amphibole asbestos fibers, which undergo no dissolution and are very 

biopersistent. Vitreous fibers with relatively high alumina and silica contents favor a relatively uniform, 

slower rate of dissolution, but increasing content of oxides of calcium, magnesium, and potassium can 
 

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3. HEALTH EFFECTS 

lead to nonuniform rates of dissolution, faster breakage, and faster clearance (Eastes et al. 2000; 

Hesterberg and Hart 2001; Morgan et al. 1994b; Potter and Mattson 1991). 

When rates of fiber deposition exceed the rates of removal, fibers can accumulate in the lung leading to 

chronic and persistent inflammation and tissue damage. For a variety of synthetic vitreous fibers and 

some amphibole asbestos fibers (amosite and crocidolite) correlations have been demonstrated among 

fiber durability in simulated pH 7.4 physiological fluids, fiber breakage rates, fiber lung clearance halftimes in rodent models, and the ability to induce prefibrotic lesions (e.g., cell proliferation or collagen 

deposition), fibrosis, or tumors in rodents following repeated inhalation exposure (Bernstein et al. 2001a, 

2001b; Eastes and Hadley 1996; Eastes et al. 2000; Hesterberg et al. 1998a). These correlations stress the 

importance of fiber durability in determining fiber pathogenicity and are the basis of proposals for using 

in vitro dissolution tests and short-term rodent lung clearance tests as preliminary screening tools to 

assess the potential toxicity of newly developed fibers. Measurements of in vitro dissolution rates for a 

number of synthetic vitreous fibers of varying chemical content indicate that substitution of sodium, 

potassium, boron, calcium, and magnesium in the silicate network tends to increase dissolution rate, 

whereas increasing aluminum oxide content tends to decrease dissolution rate. 

In support of the hypothesis that chemical composition, fiber durability, and fiber pathogenicity are 

linked, Wardenbach et al. (2000) demonstrated a significant correlation between the potencies of seven 

synthetic vitreous fibers to induce tumors in rats following intraperitoneal injection and their 

“carcinogenicity index”, which was defined as the summation of sodium-, potassium-, boron-, calcium-, 

magnesium-, and barium-oxide weight percentage minus 2 times the aluminum-oxide weight percentage. 

However, chemical composition is not expected to be the sole determinant of fiber biopersistence, as 

conditions in the manufacturing process, such as flame attenuation versus air attenuation, have been 

demonstrated to influence the dissolution rate of synthetic vitreous fibers (see Hesterberg and Hart 2001 

for review). 

3.5.2 Mechanisms of Toxicity 

The deposition of relatively insoluble particles, such as synthetic vitreous fibers, in the lower lung of 

animals is well known to cause a complex defensive inflammatory response characterized by increased 

numbers of alveolar macrophages and other inflammatory cells. Chronic and persistent inflammation 

from deposited fibers (expected with continued high level exposure to all synthetic vitreous fibers) has 
SYNTHETIC VITREOUS FIBERS 133 

3. HEALTH EFFECTS 

been linked for the most biopersistent synthetic vitreous fibers and asbestos to the development of cell 

injury, DNA changes, cell proliferation, deposition of collagen and other extracellular components 

leading to fibrosis (tissue scarring), and tumor development (Greim et al. 2001; IARC Expert Panel 1996; 

Kane 1996; Mossman and Churg 1998). Cellular and molecular events in these fiber-induced 

nonneoplastic and neoplastic effects are poorly understood, but several mechanistic hypothesis have been 

proposed based predominately on research with asbestos. The following discussion highlights results 

relevant to synthetic vitreous fibers. 

The penetration or engulfment of fibers into macrophages, other inflammatory cells, epithelial cells, or 

mesothelial cells generates reactive oxygen and nitrogen species that can damage DNA, lipids, and 

proteins, lead to cytotoxicity, and stimulate release of inflammatory mediators, cytokines, and growth 

factors that may induce epithelial and mesothelial cell proliferation (Churg et al. 2000; Driscoll 1996; 

IARC Expert Panel 1996). Reactive oxygen species may also be generated by reactions on the surfaces of 

fibers, but this activity appears to be much greater with certain asbestos fibers (e.g., amosite) than with 

insulation wools (e.g., MMVF10) and refractory ceramic (e.g., RCF1) fibers (Gilmour et al. 1995, 1997). 

Experiments with cultured cells exposed to asbestos fibers have demonstrated that anti-oxidant systems 

can protect against fiber-induced cytotoxicity, providing support for the importance of reactive oxygen 

species in the development of fiber-induced disease (Mossman and Churg 1998). 

Fibers of similar size distributions, but different chemical compositions, may elicit different responses 

from macrophages. For example, in vitro incubation of MMVF10 fibers with rat alveolar or peritoneal 

macrophages did not produce detectably increased levels of superoxide anions, but MMVF21 fibers with 

a similar distribution of fiber sizes caused increased production of superoxide anions by either type of 

macrophage (Dörger et al. 2001). This difference was associated with the finding that significantly higher 

numbers of macrophages completely phagocytized MMVF21 compared with MMVF10 fibers. The 

chemical or cellular basis for these differences is unknown, but may be related to lesser ability of 

MMVF10 fibers to directly elicit cytokines and proinflammatory mediators that modulate phagocytic 

functions of cells (Driscoll 1996). 

In addition to fiber-induced reactive oxygen-mediated mechanisms that may lead to cytotoxic and 

cytoproliferative or hyperplastic responses, other proposed mechanisms in which fibers may directly 

induce cell proliferation include: (1) a “healing” response secondary to direct fiber-induced cell injury; 

(2) direct induction by fibers (at noncytoxic levels) of inflammatory cells and other lung cells to release 
 

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3. HEALTH EFFECTS 

mediators that cause tissue damage and stimulate cell proliferation; and (3) a direct cell proliferative 

effect of fibers on cells (Driscoll 1996). It is likely that multiple mechanisms play variable roles in the 

cell proliferation responses to different fiber types and exposure scenarios. Understanding of the 

interactions among the possible multiple mechanisms is too incomplete to provide reliable in depth 

explanations for observed differences in apparent potency among fiber types, although there is sufficient 

evidence to indicate that fiber durability plays a key role. The comparative examination of cellular and 

molecular responses related to cell proliferation and inflammation from fibers with similar size 

distributions, but varying pathogenic potency, is an area of intensive current research (e.g., Barchowsky et 

al. 1997; Brown et al. 1998, 1999, 2000; Donaldson et al. 1995a, 1995b; Dörger et al. 2000, 2001; 

Gilmour et al. 1997; Jensen and Watson 1999; Johnson and Jaramillo 1997; Leikauf et al. 1995; Luoto et 

al. 1997; Marks-Konczalik et al. 1998; Morimoto et al. 1999a; Tsuda et al. 1999). 

Fiber-induced cell proliferative responses that can lead to tissue scarring in the lung and pleural tissues 

are also thought to play a role in the development of lung carcinomas or mesotheliomas by enhancing the 

frequency of cells transformed by spontaneous or fiber-induced genetic changes (Driscoll 1997; Greim et 

al. 2001; IARC Expert Panel 1996; Kane 1996). Thus, the carcinogenic responses to synthetic vitreous 

fibers observed in animals may develop via both genotoxic and non-genotoxic modes of action. As 

discussed in Section 3.3, results from in vitro tests indicate that, like asbestos fibers, several types of 

synthetic vitreous fibers can induce cytogenetic changes and alter DNA. Proposed mechanisms for fiberinduced genetic changes include DNA alterations from reactive oxygen species and physical interference 

of fibers with cellular cytoskeletons and chromosomes (Kane 1996). 

3.5.3 Animal-to-Human Extrapolations 

As discussed in Section 3.4.5, there are distinct differences between animal species and humans in 

respiratory tract size and geometry, ventilation rates and patterns, and macrophage size that influence the 

retention (the net result of deposition and clearance) of fibers in the lung. Yu and colleagues have 

developed lung retention models for refractory ceramic fibers in rats, hamsters, and humans that 

incorporate many of these interspecies differences, some of which are shown in Table 3-3 (Dai and Yu 

1998; Yu et al. 1994, 1995a, 1995b, 1996, 1997). The models incorporate mechanisms of deposition in 

the nasopharyngeal, tracheobronchial, and alveolar regions, macrophage-mediated clearance (with shorter 

fibers preferred and impaired clearance occurring at high levels of fiber lung concentration), fiber 

dissolution, and fiber transverse breakage. The rat model was also extended to lung retention of other 
SYNTHETIC VITREOUS FIBERS 135 

3. HEALTH EFFECTS 

synthetic vitreous fibers, but extension of the human model to other synthetic vitreous fibers has not been 

reported (Yu et al. 1998a, 1998b). The dosimetric models for refractory ceramic fibers predict fiber lung 

concentration as a function of time for both humans and rodents for given air concentrations of fibers with 

specified distributions of length and diameter. The models can be used to convert exposure levels in 

animal inhalation toxicity and cancer studies to human equivalent exposure levels (Appendix A describes 

the use of these models in deriving a chronic inhalation MRL for refractory ceramic fibers). As discussed 

in Section 3.4.5, several quantitative human cancer risk estimates have been prepared using the data from 

the RCF1 2-year rat bioassay and the lung deposition and clearance models developed by C.P. Yu and 

colleagues (Maxim et al. 2003b; Moolgavkar et al. 1999, 2000; Turim and Brown 2003; Yu and 

Oberdörster 2000). 

In contrast to the relatively robust understanding of fiber pharmacokinetics in animals and humans, 

understanding of the relative sensitivity of rodents and humans to synthetic vitreous fibers or asbestos 

fibers (i.e., the relative pharmacodynamics) is poor. For asbestos, rats appear to be a suitable qualitative 

model for humans given that effects observed in groups of workers exposed to high levels of airborne 

asbestos (chronic inflammation, pulmonary fibrosis, lung cancer, and mesothelioma) have also been 

observed in rat inhalation studies (Agency for Toxic Substances and Disease Registry 2001). However, 

similar qualitative comparisons between rodent and human responses to synthetic vitreous fibers are not 

possible. Available epidemiological studies of workers involved in the manufacture of fibrous glass, rock 

wool, or slag wool, or in the manufacture of refractory ceramic fibers have not found consistently 

increased risks for nonmalignant respiratory disease, lung cancer, or mesothelioma, although pulmonary 

fibrosis, lung cancer, and mesothelioma have been demonstrated in rats and hamsters exposed by 

inhalation to the most potent synthetic vitreous fibers (see Section 3.2). 

For asbestos, limited quantitative data are insufficient to conclusively determine the relative sensitivity of 

humans and rodents to fibers, although several hypotheses have been proposed on this issue. 

Rodelsperger and Woitowitz (1995) proposed that humans may be more susceptible to asbestos’s 

capability to induce mesothelioma based on a finding that lung fiber concentrations in a group of humans 

who died from asbestos-induced mesothelioma were markedly higher than concentrations in a bioassay of 

crocidolite-exposed rats. Earlier, Rowe and Springer (1986) proposed that humans and rodents may be 

equally sensitive to asbestos based on a comparison of estimated human lung cancer risks based on rodent 

inhalation bioassays and those derived in epidemiological studies of asbestos-exposed workers. Maxim 

and McConnell (2001) analyzed lung fiber concentrations associated with pulmonary fibrosis in rats and 
 

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3. HEALTH EFFECTS 

hamsters exposed to a series of asbestos (crocidolite, chrysotile) and synthetic vitreous fibers (rockwool 

MMVF21 and refractory ceramic fiber RCF1) and compared these with fiber concentrations in autopsied 

lungs from several studies of workers with asbestosis (i.e., pulmonary fibrosis from asbestos exposure). 

Estimated concentrations in rodents ranged from 1.7x106

 to 20x106 fibers (>20 μm long) per g dry lung 

compared with 1.6x106

 to 30x106 fibers (>20 μm long) per g dry lung in humans. Maxim and McConnell 

(2001) concluded, based on these and other considerations, that “there seems little reason to believe that 

humans and rats have greatly different sensitivities with respect to the development of pulmonary fibrosis 

or lung cancer.” 

3.6 TOXICITIES MEDIATED THROUGH THE NEUROENDOCRINE AXIS 

Recently, attention has focused on the potential hazardous effects of certain chemicals on the endocrine 

system because of the ability of these chemicals to mimic or block endogenous hormones. Chemicals 

with this type of activity are most commonly referred to as endocrine disruptors. However, appropriate 

terminology to describe such effects remains controversial. The terminology endocrine disruptors, 

initially used by Colborn and Clement (1992), was also used in 1996 when Congress mandated the EPA 

to develop a screening program for “...certain substances [which] may have an effect produced by a 

naturally occurring estrogen, or other such endocrine effect[s]...”. To meet this mandate, EPA convened a 

panel called the Endocrine Disruptors Screening and Testing Advisory Committee (EDSTAC), and in 

1998, the EDSTAC completed its deliberations and made recommendations to EPA concerning endocrine 

disruptors. In 1999, the National Academy of Sciences released a report that referred to these same types 

of chemicals as hormonally active agents. The terminology endocrine modulators has also been used to 

convey the fact that effects caused by such chemicals may not necessarily be adverse. Many scientists 

agree that chemicals with the ability to disrupt or modulate the endocrine system are a potential threat to 

the health of humans, aquatic animals, and wildlife. However, others think that endocrine-active 

chemicals do not pose a significant health risk, particularly in view of the fact that hormone mimics exist 

in the natural environment. Examples of natural hormone mimics are the isoflavinoid phytoestrogens 

(Adlercreutz 1995; Livingston 1978; Mayr et al. 1992). These chemicals are derived from plants and are 

similar in structure and action to endogenous estrogen. Although the public health significance and 

descriptive terminology of substances capable of affecting the endocrine system remains controversial, 

scientists agree that these chemicals may affect the synthesis, secretion, transport, binding, action, or 

elimination of natural hormones in the body responsible for maintaining homeostasis, reproduction, 

development, and/or behavior (EPA 1997). Stated differently, such compounds may cause toxicities that 
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are mediated through the neuroendocrine axis. As a result, these chemicals may play a role in altering, 

for example, metabolic, sexual, immune, and neurobehavioral function. Such chemicals are also thought 

to be involved in inducing breast, testicular, and prostate cancers, as well as endometriosis (Berger 1994; 

Giwercman et al. 1993; Hoel et al. 1992). 

No studies were located regarding the possible effects of synthetic vitreous fibers on the neuroendocrine 

axis in humans or animals or in in vitro systems. 

3.7 CHILDREN’S SUSCEPTIBILITY 

This section discusses potential health effects from exposures during the period from conception to 

maturity at 18 years of age in humans, when all biological systems will have fully developed. Potential 

effects on offspring resulting from exposures of parental germ cells are considered, as well as any indirect 

effects on the fetus and neonate resulting from maternal exposure during gestation and lactation. 

Relevant animal and in vitro models are also discussed. 

Children are not small adults. They differ from adults in their exposures and may differ in their 

susceptibility to hazardous chemicals. Children’s unique physiology and behavior can influence the 

extent of their exposure. Exposures of children are discussed in Section 6.6 Exposures of Children. 

Children sometimes differ from adults in their susceptibility to hazardous chemicals, but whether there is 

a difference depends on the chemical (Guzelian et al. 1992; NRC 1993). Children may be more or less 

susceptible than adults to health effects and the relationship may change with developmental age 

(Guzelian et al. 1992; NRC 1993). Vulnerability often depends on developmental stage. There are 

critical periods of structural and functional development during both prenatal and postnatal life and a 

particular structure or function will be most sensitive to disruption during its critical period(s). Damage 

may not be evident until a later stage of development. There are often differences in pharmacokinetics 

and metabolism between children and adults. For example, absorption may be different in neonates 

because of the immaturity of their gastrointestinal tract and their larger skin surface area in proportion to 

body weight (Morselli et al. 1980; NRC 1993); the gastrointestinal absorption of lead is greatest in infants 

and young children (Ziegler et al. 1978). Distribution of xenobiotics may be different; for example, 

infants have a larger proportion of their bodies as extracellular water and their brains and livers are 

proportionately larger (Altman and Dittmer 1974; Fomon 1966; Fomon et al. 1982; Owen and Brozek 
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3. HEALTH EFFECTS 

1966; Widdowson and Dickerson 1964). The infant also has an immature blood-brain barrier (Adinolfi 

1985; Johanson 1980) and probably an immature blood-testis barrier (Setchell and Waites 1975). Many 

xenobiotic metabolizing enzymes have distinctive developmental patterns. At various stages of growth 

and development, levels of particular enzymes may be higher or lower than those of adults, and 

sometimes unique enzymes may exist at particular developmental stages (Komori et al. 1990; Leeder and 

Kearns 1997; NRC 1993; Vieira et al. 1996). Whether differences in xenobiotic metabolism make the 

child more or less susceptible also depends on whether the relevant enzymes are involved in activation of 

the parent compound to its toxic form or in detoxification. There may also be differences in excretion, 

particularly in newborns who all have a low glomerular filtration rate and have not developed efficient 

tubular secretion and resorption capacities (Altman and Dittmer 1974; NRC 1993; West et al. 1948). 

Children and adults may differ in their capacity to repair damage from chemical insults. Children also 

have a longer remaining lifetime in which to express damage from chemicals; this potential is particularly 

relevant to cancer. 

Certain characteristics of the developing human may increase exposure or susceptibility, whereas others 

may decrease susceptibility to the same chemical. For example, although infants breathe more air per 

kilogram of body weight than adults breathe, this difference might be somewhat counterbalanced by their 

alveoli being less developed, which results in a disproportionately smaller surface area for alveolar 

absorption (NRC 1993). 

No information was located specifically concerning health effects in children exposed to synthetic 

vitreous fibers. There was no indication from the available literature that specialized respiratory defense 

mechanisms might be less active or underdeveloped in children relative to adults. Results from animal 

studies indicate that inflammation, fibrosis, and cancer of the lung or pleura are possible outcomes 

resulting from repeated inhalation exposure to certain synthetic vitreous fibers depending on the exposure 

dose, exposure duration, fiber dimensions, and fiber durability. However, no studies were located that 

have compared immature and mature animals with respect to pharmacokinetics of, or susceptibility to, 

inorganic fibers of any type (including asbestos) by any route of exposure. 

No human or animal studies were located regarding the possible developmental toxicities of synthetic 

vitreous fibers by any route of exposure. Direct effects on the developing fetus would be unexpected 

given the very small, if any, absorption of synthetic vitreous fibers by the lungs, gastrointestinal tract, or 

skin. For asbestos fibers of various types, no consistent indication of potential for developmental toxicity 
SYNTHETIC VITREOUS FIBERS 139 

3. HEALTH EFFECTS 

was indicated in several oral administration studies with rats, mice, and hamsters (Agency for Toxic 

Substances and Disease Registry 2001). 

3.8 BIOMARKERS OF EXPOSURE AND EFFECT 

Biomarkers are broadly defined as indicators signaling events in biologic systems or samples. They have 

been classified as markers of exposure, markers of effect, and markers of susceptibility (NAS/NRC 

1989). 

Due to a nascent understanding of the use and interpretation of biomarkers, implementation of biomarkers 

as tools of exposure in the general population is very limited. A biomarker of exposure is a xenobiotic 

substance or its metabolite(s) or the product of an interaction between a xenobiotic agent and some target 

molecule(s) or cell(s) that is measured within a compartment of an organism (NAS/NRC 1989). The 

preferred biomarkers of exposure are generally the substance itself or substance-specific metabolites in 

readily obtainable body fluid(s), or excreta. However, several factors can confound the use and 

interpretation of biomarkers of exposure. The body burden of a substance may be the result of exposures 

from more than one source. The substance being measured may be a metabolite of another xenobiotic 

substance (e.g., high urinary levels of phenol can result from exposure to several different aromatic 

compounds). Depending on the properties of the substance (e.g., biologic half-life) and environmental 

conditions (e.g., duration and route of exposure), the substance and all of its metabolites may have left the 

body by the time samples can be taken. It may be difficult to identify individuals exposed to hazardous 

substances that are commonly found in body tissues and fluids (e.g., essential mineral nutrients such as 

copper, zinc, and selenium). Biomarkers of exposure to synthetic vitreous fibers are discussed in 

Section 3.8.1. 

Biomarkers of effect are defined as any measurable biochemical, physiologic, or other alteration within an 

organism that, depending on magnitude, can be recognized as an established or potential health 

impairment or disease (NAS/NRC 1989). This definition encompasses biochemical or cellular signals of 

tissue dysfunction (e.g., increased liver enzyme activity or pathologic changes in female genital epithelial 

cells), as well as physiologic signs of dysfunction such as increased blood pressure or decreased lung 

capacity. Note that these markers are not often substance specific. They also may not be directly 

adverse, but can indicate potential health impairment (e.g., DNA adducts). Biomarkers of effects caused 

by synthetic vitreous fibers are discussed in Section 3.8.2. 
 

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A biomarker of susceptibility is an indicator of an inherent or acquired limitation of an organism's ability 

to respond to the challenge of exposure to a specific xenobiotic substance. It can be an intrinsic genetic or 

other characteristic or a preexisting disease that results in an increase in absorbed dose, a decrease in the 

biologically effective dose, or a target tissue response. If biomarkers of susceptibility exist, they are 

discussed in Section 3.10 “Populations That Are Unusually Susceptible.” 

3.8.1 Biomarkers Used to Identify or Quantify Exposure to Synthetic Vitreous Fibers 

Uncoated or coated fibers in bronchoalveolar lavage fluid samples or in autopsied or surgically resected 

lung tissue samples are the principal biomarkers of exposure to biopersistent asbestos fibers (Agency for 

Toxic Substances and Disease Registry 2001).1

 However, similar biomarkers to identify or quantify 

human exposure to synthetic vitreous fibers, which are less biopersistent than asbestos fibers, have not 

been developed for routine clinical use. Nevertheless, aluminum-silicate fibers with chemical 

compositions consistent with synthetic vitreous fibers have been detected in human lung tissues 

(McDonald et al. 1990; Roggli 1989; Sébastien et al. 1994) and in bronchoalveolar lavage samples 

(Dumortier et al. 2001). 

For example, among 1,800 bronchoalveolar samples submitted to a Belgium hospital between 1992 and 

1997 for fiber analysis, pseudoasbestos bodies were detected in samples from nine patients (0.5%) 

(Dumortier et al. 2001). In samples from these nine patients (all of whom had occupational experience 

with furnaces or welding), fibers of composition consistent with refractory ceramic fiber composition 

were detected in 42% of core fibers analyzed (Dumortier et al. 2001). Other nonasbestos fibers and 

asbestos fibers accounted for 28 and 30% of the core fibers analyzed in these samples, respectively. 

In another study, lung fiber concentrations were determined in autopsied tissue samples from a subset of 

deaths occurring between 1950 and 1979 in a cohort of U.S. workers involved in the manufacture of 

synthetic vitreous fibers (McDonald et al. 1990). The 145 autopsied tissue samples analyzed represented 

about 3% of the deaths that occurred in the cohort during this period. Lung fiber concentrations were 

1

 Particles or fibers that are deposited in the lung and are too large to be phagocytized by alveolar macrophages may 

become coated with an iron-rich protein coat. The generic term for these structures is ferruginous bodies. When the core fiber is 

asbestos, the resultant structure is termed an asbestos body (Agency for Toxic Substances and Disease Registry 2001). 

Ferruginous bodies having the appearance of asbestos bodies under light microscopy and a nonasbestos core fiber have been 

termed pseudoasbestos bodies (Dumortier et al. 2001). 
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compared with concentrations in 124 autopsied referents who had no known occupational experience with 

synthetic vitreous fibers, were matched for location of death (i.e., hospital), age, and year of death, and 

died from causes other than malignant disease. Lung fiber concentrations (lengths >5 μm and 

length:diameter ratio >3:1) determined by phase contrast microscopy were about 60% higher in workers 

than referents. Electron microscopy (coupled with energy dispersive spectrometry and selected area 

electron diffraction) showed no statistically significant excess of any particular type of fiber in the 

workers compared with the referents, although asbestos fibers were detected with greater frequency than 

synthetic vitreous fibers in both workers and referents. Nonasbestos fibers described as “siliceous” 

displayed a strong energy dispersive signal for silicon without sodium, aluminum, potassium, calcium, 

titanium, or iron signals and represented >90% of fibers identified as synthetic vitreous fibers. However, 

lung samples from only 26% of the workers contained any synthetic vitreous fibers. The low detection 

frequency of synthetic vitreous fibers in the worker lung samples may reflect both low exposure 

concentrations and low biopersistence of these fibers. 

In animal inhalation experiments with synthetic vitreous fibers, concentrations of fibers in the lung have 

been used to assay internal doses (e.g., Hesterberg et al. 1993c, 1999; Mast et al. 1995a, 1995b; 

McConnell et al. 1999). Based on rat experiments involving intraperitoneal injection of three different 

types of synthetic vitreous fibers, urinary levels of titanium or barium were proposed as potential 

biomarkers of exposure to synthetic vitreous fibers that contain these elements normally present in 

humans and animals in small quantities (Wastiaux et al. 1994). Reports of further development of urinary 

titatnium or barium as biomarkers of exposure to synthetic vitreous fibers were not located. 

3.8.2 Biomarkers Used to Characterize Effects Caused by Synthetic Vitreous Fibers 

Epidemiological studies of synthetic vitreous fiber manufacturing workers have not found consistent 

evidence for increased risks of malignant or nonmalignant respiratory or pleural effects, but results from 

animal experiments indicate that repeated inhalation exposure to synthetic vitreous fibers may result in 

pulmonary or pleural fibrosis, lung cancer, or mesothelioma, depending on fiber dimensions, fiber 

durability in the lung, duration of exposure, and exposure levels. 

The chest x-ray is the most common means of detecting the onset of pleural or pulmonary changes that 

may precede or accompany fibrosis (i.e., irreversible scarring of lung or pleural tissue that can lead to 

restricted breathing). The International Labour Office (ILO) established a classification system for 
 

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3. HEALTH EFFECTS 

profusion of opacities in chest x-rays that includes four categories of increasing severity, each with three 

subcategories: 0 (0/-, 0/0, 0/1); 1 (1/0, 1/1, 1/2); 2 (2/1, 2/2, 2/3); and 3 (3/2, 3/3, 3/4) (ILO 1980). The 

American Thoracic Society (1986) recommends that chest x-rays be scored for pleural and pulmonary 

changes separately because of the experience with asbestos-exposed workers indicating that pleural and 

pulmonary fibrosis have differences in “epidemiology, clinical features, and prognosis.” Computerized 

tomography (CT) and high-resolution computed tomography provide alternative techniques to the chest 

x-ray that may more sensitively detect pleural and pulmonary changes in some cases (Agency for Toxic 

Substances and Disease Registry 2001). Lung function tests are also useful to characterize the 

development of pulmonary or pleural fibrosis; forced vital capacity is diminished with increasing severity 

of pulmonary or pleural fibrosis. 

Clinical diagnostic criteria for pulmonary fibrosis include chest x-rays with small irregular opacifications 

of a profusion of 1/1 or greater, impaired forced vital capacity below the lower limit of normal, and a 

diffusing capacity below the lower limit of normal (American Thoracic Society 1986). Pleural changes 

associated with chronic inflammation from inhaled fibers or particles include pleural plaques, pleural 

fibrosis (also referred to as thickening or calcification), and pleural effusions. Pleural plaques are 

localized or diffuse areas of thickening of the pleura that appear as opaque, shiny, and rounded lesions in 

the chest x-ray. Pleural fibrosis represents a more pronounced thickening or scarring that, when severe, 

can make the pleura appear as a thick peel encasing the lung in chest x-rays. Persons with pleural fibrosis 

can experience chest pain and impaired pulmonary functions, but persons with pleural plaques alone 

usually do not (American Thoracic Society 1986). Pleural effusion is the exudation of cell-containing 

fluid from lung tissue into the pleural cavity, which is often taken as an early manifestation of exposure to 

asbestos fibers (American Thoracic Society 1986). Pleural effusions have been reported in groups of 

people exposed occupationally to asbestos (Agency for Toxic Substances and Disease Registry 2001), but 

have not been reported in workers involved in the manufacture of synthetic vitreous fibers. 

3.9 INTERACTIONS WITH OTHER CHEMICALS 

Epidemiological and clinical studies of asbestos workers have indicated that workers who smoked 

tobacco had greater risks of developing lung cancer and pulmonary fibrosis than workers who did not 

smoke, and that smoking may increase these risks by more than risks predicted by an additive model (see 

Agency for Toxic Substance and Disease Registry 2001 for review). In contrast, the studies provided no 

indication that smoking increased the risk of mesothelioma. The mechanism of this interaction is not 
 

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3. HEALTH EFFECTS 

fully understood, but there is evidence to suggest that smoking may decrease the ability of lungs to clear 

fibers or other particles. For example, the lungs of smoking workers with heavy asbestos occupational 

exposure showed higher concentrations of chrysotile and amosite fibers compared with nonsmoking 

workers (Churg and Stevens 1995), and the clearance rate of short chrysotile fibers was decreased by 30% 

in guinea pigs after coexposure to chrysotile and cigarette smoke compared with guinea pigs exposed to 

chrysotile alone (Churg et al. 1992). 

A similar interaction between smoking and inhalation exposure to synthetic vitreous fibers in jointly 

affecting lung cancer or pulmonary fibrosis is plausible, but direct evidence to support the possible 

interaction is very limited. In a study of European refractory ceramic fiber production workers, a 

statistically significant association between indices of cumulative exposure to fibers and decreased 

pulmonary function was observed in workers who smoked, but not in nonsmokers (Cowie et al. 2001; 

Rossiter et al. 1994; Trethowan et al. 1995). Alveolar macrophages from rats exposed to sidestream 

cigarette smoke produced statistically significantly greater quantities of a cytokine involved in regulating 

cellular proliferation (tumor necrosis factor) in response to chrysotile fibers in vitro than did macrophages 

from rats not exposed to smoke (Morimoto et al. 1993). Refractory ceramic fibers also induced tumor 

necrosis factor production by macrophages in vitro. Macrophages from smoke exposed rats produced 

more tumor necrosis factor than macrophages from nonexposed rats, but the difference was not 

statistically significant (Morimoto et al. 1993). The only other published finding of relevance to the 

possible interactive effects smoking and exposure to synthetic vitreous fibers is the observation that in 

vitro oxidative damage to calf thymus DNA (assayed as the formation of 8-hydroxydeoxyguanosine 

residues) produced by cigarette smoke condensate and rockwool fibers together was greater than the sum 

of the damage by each agent alone (Leanderson and Tagesson 1989). 

3.10 POPULATIONS THAT ARE UNUSUALLY SUSCEPTIBLE 

A susceptible population will exhibit a different or enhanced response to synthetic vitreous fibers than 

will most persons exposed to the same level of synthetic vitreous fibers in the environment. Reasons may 

include genetic makeup, age, health and nutritional status, and exposure to other toxic substances (e.g., 

cigarette smoke). These parameters result in reduced detoxification or excretion of synthetic vitreous 

fibers, or compromised function of organs affected by synthetic vitreous fibers. Populations who are at 

greater risk due to their unusually high exposure to synthetic vitreous fibers are discussed in Section 6.7, 

Populations With Potentially High Exposures. 
 

 

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3. HEALTH EFFECTS 

Persons with impaired pulmonary clearance mechanisms (e.g., due to chronic exposure to cigarette smoke 

or repeated exposure to dusty air leading to high burdens of particles in the lung) or genetically 

determined relatively poor ability to detoxify reactive oxidative molecules produced during pulmonary 

disposition of fibers (e.g., reactive oxygen radicals or nitrogen oxide) may be more susceptible than others 

to possible nonmalignant or malignant pulmonary or pleural disorders from chronic exposure to synthetic 

vitreous fibers. Direct evidence in support of these hypotheses, however, is lacking for synthetic vitreous 

fibers, except for the observation that cumulative exposure indices were associated with decreased 

pulmonary function in European refractory ceramic fiber workers who smoked, but not in nonsmokers 

(Cowie et al. 2001; Rossiter et al. 1994; Trethowan et al. 1995). 

In case-control studies of asbestos-exposed persons, associations have been observed between deletion of 

the gene (GSTM1) encoding one class of glutathione S-transferase (GSTμ), an enzyme that protects 

against oxidative tissue damage, and increased risks for mesothelioma, other cancers, or nonmalignant 

pulmonary disorders (Hirvonen 1997; Hirvonen et al. 1996; Kelsey et al. 1997). Increased risks for 

developing nonmalignant pulmonary disorders or mesothelioma were also observed among persons with 

histories of high-level asbestos exposure who lacked the GSTM1 gene and had a slow genotype for 

N-acetyltransferase 2 (NAT2), compared with risks in exposed subjects with the GSTM1 gene and the 

fast NAT2 genotype (Hirvonen et al. 1996). Slow acetylation by NAT2 may lead to accumulation of 

polyamines that stimulate cell proliferation. 

3.11 METHODS FOR REDUCING TOXIC EFFECTS 

This section will describe clinical practice and research concerning methods for reducing toxic effects of 

exposure to synthetic vitreous fibers. However, because some of the treatments discussed may be 

experimental and unproven, this section should not be used as a guide for treatment of exposures to 

synthetic vitreous fibers. When specific exposures have occurred, poison control centers and medical 

toxicologists should be consulted for medical advice. The following texts provide specific information 

about treatment following exposures to synthetic vitreous fibers: 

Standard texts of medical toxicology (e.g., Ellenhorn et al. 1997; Goldfrank et al. 1998) do not provide 

specific information about treatment of acute irritation effects or possible chronic effects from exposure to 

synthetic vitreous fibers, but recommend minimizing exposure. Since the early 1990s, manufacturers of 
SYNTHETIC VITREOUS FIBERS 145 

3. HEALTH EFFECTS 

synthetic vitreous fibers have been making modifications to new products in order to make them more 

biosoluble (i.e., less biopersistent) and potentially less hazardous than older products (Hesterberg and 

Hart 2001; IARC 2002). 

3.11.1 Reducing Peak Absorption Following Exposure 

Absorption of synthetic vitreous fibers is expected to be negligible following inhalation, ingestion, or 

dermal exposure. Recommendations have been made to avoid contact with the fibers by wearing 

protective clothing and using ocular and respiratory protection when working with materials containing 

synthetic vitreous fibers and to minimize physical disturbance of the material and generation of dusts, in 

order to avoid the acute dermal, respiratory, or ocular irritation experienced from contact with synthetic 

vitreous fibers (e.g., “fiberglass itch”), and prevent the possible pulmonary or pleural disorders from 

chronic inhalation exposure (Ellenhorn et al. 1997; Goldfrank et al. 1998; Jeffress 1999; Mentzer 1999; 

OSHA 1999). Rinsing of exposed areas with water also minimizes contact. 

3.11.2 Reducing Body Burden 

As discussed in Section 3.4, the principal pathways by which inhaled and deposited synthetic vitreous 

fibers are removed from the respiratory tract involve: (1) direct or macrophage-mediated mechanical 

mucociliary translocation to the pharynx, swallowing into the gastrointestinal tract, and elimination in the 

feces; (2) dissolution; and (3) transverse breakage of long fibers into shorter fibers. To date, there are no 

clinical methods to enhance or supplement these natural methods of elimination of inhaled fibers that 

deposit on the epithelial surfaces of the respiratory tract. 

3.11.3 Interfering with the Mechanism of Action for Toxic Effects 

The mechanisms by which repeated exposure to airborne synthetic vitreous fibers may cause pulmonary 

or pleural disorders are poorly understood (see Section 3.5), and there are no tested methods of 

interference. It is plausible that repeated exposure to the more durable synthetic vitreous fibers could also 

cause pulmonary or pleural disorders in humans as it has been observed to do in laboratory rodents. 
 

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3. HEALTH EFFECTS 

3.12 ADEQUACY OF THE DATABASE 

Section 104(i)(5) of CERCLA, as amended, directs the Administrator of ATSDR (in consultation with the 

Administrator of EPA and agencies and programs of the Public Health Service) to assess whether 

adequate information on the health effects of synthetic vitreous fibers is available. Where adequate 

information is not available, ATSDR, in conjunction with the National Toxicology Program (NTP), is 

required to assure the initiation of a program of research designed to determine the health effects (and 

techniques for developing methods to determine such health effects) of synthetic vitreous fibers. 

The following categories of possible data needs have been identified by a joint team of scientists from 

ATSDR, NTP, and EPA. They are defined as substance-specific informational needs that if met would 

reduce the uncertainties of human health assessment. This definition should not be interpreted to mean 

that all data needs discussed in this section must be filled. In the future, the identified data needs will be 

evaluated and prioritized, and a substance-specific research agenda will be proposed. 

3.12.1 Existing Information on Health Effects of Synthetic Vitreous Fibers 

The existing data on health effects of inhalation, oral, and dermal exposure of humans and animals to 

synthetic vitreous fibers are summarized in Figure 3-2. The purpose of this figure is to illustrate the 

existing information concerning the health effects of synthetic vitreous fibers. Each dot in the figure 

indicates that one or more studies provide information associated with that particular effect. The dot does 

not necessarily imply anything about the quality of the study or studies, nor should missing information in 

this figure be interpreted as a “data need”. A data need, as defined in ATSDR’s Decision Guide for 

Identifying Substance-Specific Data Needs Related to Toxicological Profiles (Agency for Toxic 

Substances and Disease Registry 1989), is substance-specific information necessary to conduct 

comprehensive public health assessments. Generally, ATSDR defines a data gap more broadly as any 

substance-specific information missing from the scientific literature. 

3.12.2 Identification of Data Needs 

Acute-Duration Exposure. As discussed in Section 3.2, acute occupational exposure to synthetic 

vitreous fibers including fiberglass fabrics and insulation materials has been associated with reversible 
Death

Acute 

Intermediate 

Chronic 

Immunologic/Lymphoretic 

Neurologic 

Reproductive 

Developmental 

Genotoxic 

Cancer 

Systemic 

Human 

Inhalation 

Oral 

Dermal 

Death

Acute 

Intermediate 

Chronic 

Immunologic/Lymphoretic 

Neurologic 

Reproductive 

Developmental 

Genotoxic 

Cancer 

Systemic 

Animal 

Inhalation 

Oral 

Dermal 

Existing Studies 

SYNTHETIC VITREOUS FIBERS 147 

3. HEALTH EFFECTS 

Figure 3-2. Existing Information on Health Effects of Synthetic Vitreous Fibers 
SYNTHETIC VITREOUS FIBERS 148 

3. HEALTH EFFECTS 

symptoms of irritation of the upper respiratory tract (ACGIH 2001; Horvath 1995; Milby and Wolf 1969; 

Nasr et al. 1971; Newball and Brahim 1976; Petersen and Sabroe 1991; Thriene et al. 1996), the skin 

(Bendsoe et al. 1987; Bjornberg 1985; Bjornberg and Lowhagen 1977; Bjornberg et al. 1979a, 1979b, 

1979c; Eun et al. 1991 Fisher 1982; Fisher and Warkentin 1969; Heisel and Hunt 1968; KiecSwierczynska and Szymczk 1995; Koh and Khoo, 1995; Longley and Jones 1966; Peterson and Sabroe 

1991; Possick et al. 1970; Stam-Westerveld et al. 1994; Tarvainen et al. 1993; Thriene et al. 1996), and 

the eyes (Longley and Jones 1966; Petersen and Sabroe 1991; Stokholm et al. 1982). The skin irritation 

has been associated with fibers of diameter >5 μm and often becomes less pronounced with continued 

exposure (ACGIH 2001; Heisel and Hunt 1968; Stam Westerveld et al. 1994). 

The available human data adequately identify reversible skin irritation as a concern from acute dermal 

exposure. The data support occupational health and public health recommendations to limit dermal 

contact and airborne exposure by limiting the generation of dusts from materials containing synthetic 

vitreous fibers and by wearing loose protective clothing, gloves, and ocular and respiratory protection 

when handling the material. 

Acute inhalation studies in animals are limited to rodent studies with RCF1 that observed pulmonary and 

pleural inflammation (Everitt et al. 1994; Gelzleichter et al. 1996a, 1996c). Other studies have observed 

nonneoplastic and neoplastic health effects caused by injection or implantation (e.g., single acute dosing) 

of synthetic vitreous fibers into the intraperitioneal or intrapleural cavities of animals (Adachi et al. 1991; 

Davis et al. 1984; Feron et al. 1985; Mohr et al. 1984; Pickrell et al. 1983; Pigott and Ishmael 1981; Pott 

et al. 1987; Renne et al. 1985; Smith et al. 1987; Stanton and Wrench 1972; Stanton et al. 1977; Wright 

and Kuschner, 1977). Their relevance to human inhalation exposure is unclear because of the high doses 

and rapid dose rates used, the bypassing of the natural defense systems of the nasal and upper respiratory 

system, and the overloading or lack (for intraperitoneal studies) of pulmonary clearance mechanisms. No 

acute inhalation MRL was derived because data describing dose-response relationships for irritation of 

the upper respiratory tract in humans or animals are not available. 

No acute-duration oral exposure studies in humans or animals were identified. The oral route of exposure 

is not of public health concern for synthetic vitreous fibers; therefore, no data need is identified. 

Intermediate-Duration Exposure. Epidemiologic studies involving inhalation exposure have 

tended to exclude persons with intermediate-duration (<1 year) exposure, due to associated confounding 
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factors. In animals, multiple exposure-level experiments were conducted for RCF1, the glass wools 

MMVF10 and MMVF11, the rock wool MMVF21, and the slag wool MMVF22 (Hesterberg et al. 1999; 

Mast et al. 1995b; McConnell et al. 1994), but other fiber types were tested only at single (usually high) 

concentrations. The studies were designed as chronic studies, but include interim sacrifice data 

describing dose-response relationships for effects from intermediate-duration inhalation exposure. 

Virtually all of the fibers tested caused reversible pulmonary inflammation, including the refractory 

ceramic fibers RCF1, RCF2, RCF3, and RCF4, the insulation glass wools MMVF10 and MMVF11, the 

rock wool MMVF21, the slag wool MMVF22, the durable glass fiber MMVF33, the high-temperature 

rock wool MMVF 34, the high-silica synthetic vitreous fiber X607, the special-purpose 104E-glass fiber, 

GB100R glass wool, and C102/C104 blend fibrous glass (Cullen et al. 2000; Goldstein et al. 1983; 

Haratake et al. 1995; Hesterberg et al. 1993c, 1998b; Kamstrup et al. 2001; Mast et al. 1995a, 1995b; 

McConnell et al. 1994, 1999). Only one study reported a NOAEL, for Code 104 glass wool (Muhle et al. 

1987). 

Interstitial or pleural fibrosis was seen in rodents exposed to the refractory ceramic fibers RCF1, RCF2, 

RCF3, and RCF4, the durable glass fiber MMVF33, and the special purpose 104E-glass following 

intermediate-duration exposure (Cullen et al. 2000; Mast et al. 1995a, 1995b; McConnell et al. 1999), but 

no increase in fibrosis was seen in animals exposed to MMVF10, MMVF11, MMVF34, or 

X607 (Hesterberg et al. 1993c, 1998b; Kamstrup et al. 2001; McConnell et al. 1999). 

The available animal data adequately identify pulmonary or pleural effects as potential health hazards 

from intermediate-duration inhalation exposure to synthetic vitreous fibers. The data also provide 

adequate descriptions of dose-response relationships for these effects in rats from samples of glass wools, 

rock wool, slag wool, and refractory ceramic fibers. 

A chronic inhalation MRL was derived for the refractory ceramic fiber, RCF1, based on pulmonary 

inflammation in rats as the critical effect (see Section 2.3 and Appendix A). The MRL derivation used rat 

and human lung deposition and clearance models to extrapolate rat exposure levels to human equivalent 

concentrations and was based on the assumption that the responses in rats would occur in humans at the 

same dose of fibers deposited in the alveolar region of the lung. The interim sacrifice data from the 

chronic study indicated that dose-response relationships for this effect were similar for chronic and 

intermediate durations. Although an intermediate inhalation MRL for refractory ceramic fibers was not 
 

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derived, the data indicate that it would be similar to the chronic MRL. It is expected that the chronic 

MRL can be used reliably to assess effects from intermediate-duration exposures. Additional data for 

intermediate-duration exposure to RCF1 do not appear to be needed. 

Adequate rat data are also available for intermediate and chronic inhalation exposure to MMVF10, 

MMVF11, MMVF21, and MMVF22. However, no intermediate or chronic inhalation MRLs were 

derived because of the uncertainty in extrapolating from rats to humans in the absence of human lung 

deposition and clearance models for these synthetic vitreous fibers. However, when such models are 

available, the rat studies will provide adequate data for deriving intermediate and chronic inhalation 

MRLs for glass wool, rock wool, and slag wool. 

No intermediate-duration oral or dermal exposure studies in humans or animals were identified. Repeated 

exposure by the oral route is of relatively low concern for the general population; therefore, no data need 

has been identified at this time. For dermal exposure, the available data demonstrating acute reversible 

skin irritation from direct contact with insulation materials containing synthetic vitreous is adequate to 

support public health recommendations to wear gloves and protective clothing (and other protective 

devices including eye and respiratory protection) when handling materials containing synthetic vitreous 

fibers. No data need has been identified for potential health effects from intermediate-duration dermal 

exposure. 

Chronic-Duration Exposure and Cancer. The most biologically significant effect found in 

retrospective and longitudinal evaluations of the health of workers involved in the manufacture of 

refractory ceramic fibers in the United States (LeMasters et al. 1994; Lentz et al. 2003; Lockey et al. 

1996, 2002) and Europe (Cowie et al. 2001; Trethowan et al. 1995) is a low prevalence of pleural plaques 

(about 3%). However, consistent statistically significant associations with exposure to refractory ceramic 

fibers were only found in the U.S. cohort (Lentz et al. 2003; Lockey et al. 1996, 2002). Consistent 

exposure-related effects on pulmonary function have not been found in these cohorts (Burge et al. 1995; 

Cowie et al. 2001; Lockey et al. 1998). 

Adverse findings in cross-sectional health evaluation studies of workers involved in the manufacture of 

continuous glass fibers, glass wool, or rock and slag wool are restricted to elevated prevalences of selfreported respiratory symptoms (e.g., coughing, bronchitis) (Albin et al. 1998; Clausen et al. 1993; 

Engholm and von Schmalensee 1982; Kilburn et al. 1992); evidence for elevated prevalences of pleural 
 

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plaques in these workers is inadequate (Hughes et al. 1993; Kilburn and Warshaw 1991; Kilburn et al. 

1992; Sanden and Jarvholm 1986; Scansetti et al. 1993; Weill et al. 1983). 

Cohort mortality and case-control studies have tracked nonneoplastic and neoplastic causes of mortality 

among groups of workers involved in the manufacture of fibrous glass, rock wool, or slag wool without 

finding conclusive evidence of increased risks associated with exposure (Bayliss et al. 1976; Bertazzi et 

al. 1986; Boffetta et al. 1999; Buchanich et al. 2001; Chiazze et al. 1992, 1993, 1995, 1997, 2002; 

Enterline and Henderson 1975; Kjaerheim et al. 2001; Marsh et al. 1990, 2001a, 2001b, 2001c; Morgan 

1981; Sali et al. 1999; Saracci et al. 1984; Shannon et al. 1984, 1987, 1990; Simonato et al. 1986a, 1987; 

Watkins et al. 1997). Similar cohort mortality or case-control studies of workers involved in the 

manufacture of refractory ceramic fibers are restricted to a mortality study of male workers employed at 

two U.S. manufacturing plants (LeMasters et al. 2003). In an initial report of the mortality experience of 

this cohort (about 90% of which is still alive), the only statistically significant excess mortality was for 

deaths associated with cancer of the urinary system. No mesotheliomas and no excess deaths associated 

with respiratory cancers or nonmalignant respiratory disease were found. The excess urinary cancer 

deaths may be a chance finding given the wide confidence interval for the SMR, the large number of 

statistical tests (n=46) that were conducted, and the lack of a plausible mechanistic explanation of how 

fibers may increase the risk for urinary cancer mortality. Continued monitoring of the mortality 

experience of this cohort is planned. 

In animals, chronic-duration inhalation studies were primarily continuations of intermediate-duration 

studies, with pulmonary inflammation observed for all fibers tested and fibrosis observed for the 

refractory ceramic fibers and MMVF 33 (see Section 3.2). The special-purpose 104E-glass was not tested 

in a chronic-duration study. Although C102/C104 blend fibrous glass was not fibrogenic at 8 months, 

pulmonary fibrosis was observed by 18 months (Goldstein et al. 1983). Pleural mesotheliomas were 

observed in rodents exposed to refractory ceramic fibers (RCF1, RCF2, and RCF3), MMVF33, and 

104E-glass (Cullen et al. 2000; Mast et al. 1995a; McConnell et al. 1999; Smith et al. 1987). Lung tumor 

incidence (adenomas, carcinomas, or the combined incidence) were elevated in rodents exposed to RCF1, 

RCF2, RCF3, RCF4, or 104E-glass (Cullen et al. 2000; Mast et al. 1995a, 1995b; McConnell et al. 1995), 

but not in studies with other synthetic vitreous fibers including MMVF10, MMVF11, MMVF 21, 

MMVF22, MMVF34, Code 104 glass wool, GB100R glass wool, high-silica synthetic vitreous fiber 

X607, or special-purpose 100/475 glass microfiber (Cullen et al. 2000; Goldstein et al. 1983; Haratake et 
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al. 1995; Hesterberg et al. 1993c, 1998b; Kamstrup et al. 2001; Mast et al. 1995a, 1995b; McConnell et 

al. 1994, 1999; Muhle et al. 1987). 

As discussed in the previous section, a chronic inhalation MRL was derived for the refractory ceramic 

fiber, RCF1, based on pulmonary inflammation in rats as the critical effect (see Section 2.3 and 

Appendix A). One area of uncertainty associated with the critical study for the chronic MRL is the 

degree to which the dose-response relationship for pulmonary inflammation is affected by the nonfibrous 

particles in the aerosols to which the rats were exposed. Nonfibrous particles (with aspect ratios <3:1) 

have been reported to account for about 25% of the mass in RCF1 aerosols (Bellmann et al. 2001). 

Results from 3-week exposure studies with rats suggest that pulmonary responses to RCF1a, a material 

with only 2% of its mass accounted for by nonfibrous particles, are less severe than those induced by 

RCF1 at similar exposure levels (Bellmann et al. 2001). Additional research may be useful to 

quantitatively determine the effect of nonfibrous particles on the dose-response relationship for 

pulmonary inflammation from chronic exposure to refractory ceramic fibers. 

Adequate rat data are also available for intermediate and chronic inhalation exposure to the glass wools, 

MMVF10 and MMVF11, a rock wool, MMVF21, and a slag wool, MMVF22. However, no intermediate 

or chronic inhalation MRLs were derived because of the uncertainty in extrapolating from rats to humans 

in the absence of human lung deposition and clearance models for these synthetic vitreous fibers. When 

such models are available, the rat studies will provide adequate data for deriving intermediate and chronic 

inhalation MRLs for glass wool, rock wool, and slag wool. 

Workers involved in the installation or removal of insulation materials with synthetic vitreous fibers are 

expected to be exposed to higher airborne levels of fibers than manufacturing workers, but research that 

monitored health status and mortality patterns in groups of these types of workers is limited. Additional 

longitudinal monitoring of the respiratory health of insulation workers (and their exposure conditions) 

may be helpful in a better assessment of the health safety of their work environment. 

No chronic-duration oral or dermal exposure studies in humans or animals were identified, although 

experimental studies with human subjects, case reports, and occupational exposure experience document 

the well-known acute, but reversible, skin irritation caused by direct dermal contact with insulation glass 

wools. Repeated exposure by these routes is not of high concern for the general public; therefore, no data 

needs for these routes have been identified at this time. Reinforcing the lack of concern for health effects 
 

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by oral exposure to fibrous materials, results from several studies of rats exposed for life to several types 

of asbestos found no convincing evidenc for nonmalignant disease in the exposed rats (Agency for Toxic 

Substances and Disease Registry 2001). 

Genotoxicity. No evidence for genotoxic activity of several synthetic vitreous fibers was found in 

bacterial mutation assays (Chamberlain and Tarmy 1977) or sister chromatid exchange assays in cultured 

human cells (Casey 1983). However, cytogenetic effects induced by synthetic vitreous fibers in 

mammalian cells in vitro include chromosomal aberrations (Brown et al. 1979a, 1979b); morphological 

transformations (Gao et al. 1995; Hesterberg and Barrett 1984; Hesterberg et al. 1985; Oshimura et al. 

1984; Whong et al. 1999); micronuclei and multinuclei (Dopp and Schiffmann 1998; Dopp et al. 1997; 

Hart et al. 1992; Ong et al. 1997; Peraud and Riebe-Imre 1994; Zhong et al. 1997); polyploidy (Koshi et 

al. 1991; Sincock et al. 1982); and DNA strand breaks and DNA-DNA interstrand crosslinks (Wang et al. 

1999b). In addition, several synthetic vitreous fiber types have been demonstrated to damage isolated 

DNA (Donaldson et al. 1995c) and to hydroxylate 2-deoxyguanosine to 8-hydroxydeoxyguanosine, 

presumably via hydroxyl radicals (Leanderson et al. 1988, 1989). 

There is evidence that fiber dimensions can influence in vitro cytogenetic activities (Hesterberg and 

Barrett 1984; Hesterberg et al. 1985; Ong et al. 1997) and that synthetic vitreous fibers are often less 

genotoxically active than asbestos fibers (e.g., Donaldson et al. 1995c; Janssen et al. 1994a; Leanderson et 

al. 1988, 1989; Peraud and Rieve-Imre 1994; Wang et al. 1999b). For example, thin glass fibers 

(diameters 0.1–0.2 μm, lengths >10 μm) were very active in transforming Syrian hamster embryo cells, 

whereas thick glass fibers (diameter about 0.8 μm) were much less potent (Hesterberg and Barrett 1984). 

Milling of the thin glass fibers to reduce the length to <1 μm diminished the transforming activity. 

The available evidence is sufficient to suggest that synthetic vitreous fibers may produce cytogenetic 

changes in in vitro systems, but data regarding in vivo genotoxicity is lacking. In vivo data may be 

helpful to further assess the genotoxic potential of synthetic vitreous fibers. 

Reproductive Toxicity. There are no studies in humans or animals on the potential for synthetic 

vitreous fibers to produce reproductive effects. Given the limited degree to which synthetic vitreous 

fibers are absorbed into the body, there is no mechanistic basis to suspect that reproductive effects may be 

of concern from exposure to synthetic vitreous fibers. No data needs have been identified at this time. 
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Developmental Toxicity. There are no studies in humans or animals on the potential for synthetic 

vitreous fibers to produce developmentally toxic effects. As with reproductive toxicity, there is no 

empirical or mechanistic basis to suspect that developmental effects may be of concern from exposure to 

synthetic vitreous fibers. No data needs have been identified at this time. 

Immunotoxicity. There are no studies in humans or animals specifically designed to examine the 

potential for synthetic vitreous fibers to affect the immunological or lymphoreticular systems following 

inhalation, oral, or dermal exposures. There are several reports of immune system depression in asbestosexposed workers who developed asbestosis or cancer (see Agency for Toxic Substance and Disease 

Registry 2001), but whether or not the depression was directly caused by asbestos or by the diseased state 

is unknown. Given the lack of increased reporting of symptoms of allergy or immune system depression 

in health surveillance studies of workers involved in the manufacture of refractory ceramic fibers or 

insulation wools (Clausen et al. 1993; Cowie et al. 2001; Ernst et al. 1987; Gross 1976; Hansen et al. 

1999; Hill et al. 1973; Hughes et al. 1993; Kilburn et al. 1992; LeMasters et al. 1998; Lockey et al. 1998; 

Moulin et al. 1988; Nasr et al. 1971; Sanden and Jarvholm 1986; Trethowan et al. 1995; Weill et al. 1983; 

Wright 1968), immunological effects do not appear to be a critical public health concern from exposure to 

synthetic vitreous fibers. No data needs have been identified at this time. 

Neurotoxicity. There are no studies in humans or animals on the potential for synthetic vitreous fibers 

to produce neurotoxic effects. As with reproductive and developmental toxicity, there is no empirical or 

mechanistic basis to suspect that neurotoxic effects may be of concern from exposure to synthetic vitreous 

fibers. No data needs have been identified at this time. 

Epidemiological and Human Dosimetry Studies. Studies of workers predominately involved in 

the manufacture of fibrous glass materials have focused on the prevalence of respiratory symptoms 

through the administration of questionnaires, pulmonary function testing, and chest x-ray examinations 

(Clausen et al. 1993; Gross 1976; Hill et al. 1973; Hughes et al. 1993; Nasr et al. 1971; Weill et al. 1983; 

Wright 1968). In general, these studies reported no consistent evidence for increased prevalence of 

adverse respiratory symptoms, abnormal pulmonary functions, or chest x-ray abnormalities; however, one 

study reported altered pulmonary function (decreased forced expiratory volume in 1 second) in a group of 

Danish insulation workers compared with a group of bus drivers (Clausen et al. 1993). Longitudinal 

health evaluations of workers involved in the manufacture of refractory ceramic fibers, fibrous glass, rock 

wool, or slag wool have not found consistent evidence of exposure-related changes in chest x-rays or 
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pulmonary functions, with the exception that pleural plaques were found in about 3% of examined U.S. 

refractory ceramic fiber manufacturing workers and that pleural plaque prevalence showed statistically 

significant trends with increasing exposure categories (LeMasters et al. 1994; Lentz et al. 2003; Lockey et 

al. 1996, 2002). 

Epidemiologic studies (cohort mortality and case-control studies) of causes of mortality among groups of 

workers involved in the manufacture of fibrous glass, rock wool, or slag wool provide no consistent 

evidence for increased risks of mortality from nonmalignant respiratory disease, lung cancer, or pleural 

mesothelioma (Bayliss et al. 1976; Bertazzi et al. 1986; Boffetta et al. 1999; Buchanich et al. 2001; 

Chiazze et al. 1992, 1993, 1995, 1997, 2002; Enterline and Henderson 1975; Kjaerheim et al. 2002; 

Marsh et al. 1990, 2001a, 2001b, 2001c; Morgan 1981; Sali et al. 1999; Saracci et al. 1984; Shannon et al. 

1984, 1987, 1990; Simonato et al. 1986a, 1987; Watkins et al. 1997). In an initial report of the only 

available cohort mortality study of refractory ceramic fiber workers, the only statistically significant 

excess mortality was for deaths associated with cancer of the urinary system (LeMasters et al. 2003). No 

mesotheliomas and no excess deaths associated with respiratory cancers or nonmalignant respiratory 

disease were found. Continued monitoring of the mortality experience of this cohort is planned. 

As discussed in the “Chronic-Duration Exposure and Cancer” section, workers involved in the installation 

or removal of insulation materials with synthetic vitreous fibers are expected to be exposed to higher 

airborne levels of fibers than manufacturing workers, but monitoring of the health status and mortality 

patterns in groups of these types of workers is limited. Additional longitudinal monitoring of the 

respiratory health of groups of insulation workers (and their exposure conditions) may be helpful in a 

better assessment of the health safety of their work environment. 

Biomarkers of Exposure and Effect. 

Exposure. The most pertinent parameter for measuring exposure to synthetic vitreous fibers would be 

retained or deposited dose of fibers in the lung, a biomarker that is invasive and impossible to determine 

without autopsy or resection. The detection and chemical identification of fibers in bronchoalveolar 

lavage or sputum samples has been proposed as less invasive biomarkers of exposure to asbestos (Agency 

for Toxic Substances and Disease Registry 2001) and synthetic vitreous fibers (Dumortier et al. 2001), 

but these methods have not been fully developed as quantitative biomarkers of exposure. Further 
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development of noninvasive biomarkers of exposure may be useful to monitor workers exposed to dusty 

working conditions when installing or removing materials containing synthetic vitreous fibers. 

Effect. No specific and sensitive biomarkers of disease induced by synthetic vitreous fibers are known. 

The chest x-ray represents the most widely used method to detect nonneoplastic and neoplastic lesions in 

the lung or pleura that may occur (as indicated by animal experiments) after long-term exposure to 

synthetic vitreous fibers (American Thoracic Society 1986). However, the chest x-ray would detect 

changes only after significant injury has occurred and would not indicate directly whether or not the 

changes were caused by synthetic vitreous fibers or some other lung toxicant such as cigarette smoke or 

asbestos. Computerized tomography has shown some promise for detecting early asbestos-related effects 

such as pleural plaques or thickening (Agency for Toxic Substances and Disease Registry 2001), and may 

be useful to monitor the health of workers repeatedly exposed to high levels of airborne synthetic vitreous 

fibers. Tests of lung function also detect relatively early signs of effects from lung toxicants, but provide 

only limited information regarding the possible cause. Given the evidence that pulmonary or pleural 

effects are not expected at airborne concentrations below current recommendations for occupational 

exposure limits (1 fiber/cc for insulation wools and 0.2 fiber/cc for refractory ceramic fibers; ACGIH 

2001), current methods to monitor possible effects from synthetic vitreous fibers appear adequate, albeit 

lacking in specificity (i.e., chest x-ray, lung function tests, and computerized tomography). No data needs 

have been identified at this time. 

Absorption, Distribution, Metabolism, and Excretion. As discussed in Section 3.4, rates of 

absorption of synthetic vitreous fibers across the epithelial layers of the respiratory tract, the 

gastrointestinal tract, and the skin are expected to be negligible given the relatively large physical 

dimensions of these elongated particles. The toxicokinetic variables of greatest relevance to the exposure 

route of greatest public health concern (inhalation) are: the extent and location of fiber deposition in the 

respiratory tract; the rates of deposited fiber removal by mucociliary transport, macrophage-mediated 

engulfment and clearance, and dissolution in lung fluid; and the translocation of fibers within and across 

the lung. These variables are of toxicological interest because fibers can accumulate in the lung leading 

to chronic and persistent pulmonary inflammation and, for the more durable synthetic vitreous fibers, 

tissue damage when rates of fiber deposition exceed rates of removal. For a variety of synthetic vitreous 

fibers and some amphibole fibers (which do not undergo dissolution in lung fluid), correlations have been 

demonstrated between the ability to induce pulmonary or pleural inflammation or tissue damage and 

several of these variables, including dissolution rates in synthetic lung fluid, fiber breakage rates, and 
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3. HEALTH EFFECTS 

fiber lung clearance half-times (Bernstein et al. 2001a, 2001b; Eastes and Hadley 1996; Eastes et al. 2000; 

Hesterberg et al. 1998a). 

For several types of synthetic vitreous fibers, these processes have been well studied in animals, but not 

directly in human subjects. The animal study results provide enough information to support the 

development of models that predict lung deposition and retention of inhaled refractory ceramic fibers and 

other synthetic vitreous fibers (glass wools and rock wools) in rats (Yu et al. 1994, 1995b, 1996, 1998a, 

1998b). Good agreement has been observed between model predictions and observed concentrations of 

fibers in the lungs of rats exposed to aerosols of refractory ceramic fibers or insulation wools for 

intermediate or chronic durations. Models to predict the deposition and retention of inhaled refractory 

ceramic fibers in humans have been developed based on known anatomical and physiological differences 

between rats and humans (Yu et al. 1995a, 1997). In the only testing of the human model, it was used to 

predict exposure concentrations from autopsied lung concentration data for three refractory ceramic fiber 

manufacturing workers (Yu et al. 1997). The predicted exposure concentrations were within the range of 

air concentrations measured for some manufacturing plants. 

Models for lung retention and clearance of other synthetic vitreous fibers have not been developed. 

Development of human models for insulation wools will decrease uncertainty in extrapolating from 

chronic inhalation data for pulmonary inflammation in rats and facilitate the derivation of intermediateand chronic-duration inhalation MRLs for these materials. Additional research to compare predictions 

from the human models with lung concentration data for human subjects with known exposures may help 

to decrease uncertainty in the validity of the model predictions. 

The lung deposition and retention models incorporate information from the animal studies that the 

fraction of inhaled synthetic vitreous fibers deposited on the epithelial surfaces of the respiratory tract and 

the region where deposition occurs are determined by fiber dimensions, fiber mass density, ventilation 

parameters, and the structure and airway size of the respiratory tract (Dai and Yu 1998; Lippmann 1990; 

Morgan 1995; Yu et al. 1995a). Fibers with aerodynamic diameters >3–5 μm are predominately 

deposited in the upper airways and do not travel to the lower lung where gas exchange occurs. Fibers 

deposited in the upper airways are quickly removed by mucociliary transport to the pharynx and 

swallowing. The models also incorporate information from animal studies illustrating the following 

features of clearance of synthetic vitreous fibers from the lower lung: (1) fibers are cleared from the 

lower gas exchange region by macrophage engulfment and transport; (2) fibers longer than the diameter 
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of macrophages are poorly engulfed and cleared (i.e., shorter fibers are more rapidly cleared than longer 

fibers); (3) macrophage-mediated clearance is dependent on lung burden of particles (the rate of clearance 

slows at high lung burdens); (4) dissolution of synthetic vitreous fibers occurs in lung fluid (the 

dissolution rate varies with fibers of varying chemical composition); and (5) partially dissolved fibers 

more readily break into shorter fibers. The models do not describe translocation of deposited fibers from 

the lower lung into pleural tissue or the lymphatic system, although there is evidence from animal studies 

that small numbers of short and thin fibers are rapidly translocated to pleural tissues (Everitt et al. 1997; 

Gelzleichter et al. 1996a, 1999) and that translocation to lymph nodes can be considerable only under 

conditions that overload macrophage-mediated clearance mechanisms (Lee et al. 1981a; Morgan et al. 

1982). Additional research on the extent and rate of translocation of fibers into pleural tissue, and 

conditions governing this process, may be useful in providing more a specific description of the target 

organ dose-response relationship for pleural effects (pleural fibrosis and mesothelioma) observed in rats 

exposed to the most durable of synthetic vitreous fibers, refractory ceramic fibers. 

There are no toxicokinetic studies in humans or animals following oral or dermal exposure. Absorption 

and retention in the gastrointestinal tract and the skin are expected to be negligible. No data needs are 

identified at this time for toxicokinetic data for these routes of exposure. 

Comparative Toxicokinetics. As discussed in Sections 3.4 and 3.5.3, differences in respiratory tract 

size and geometry, ventilation rates and patterns, and macrophage size between animal species and 

humans are expected to influence the retention of synthetic vitreous fibers in the lung. Lung deposition 

and clearance models that incorporate many of these interspecies differences have been developed for 

refractory ceramic fibers in rats, hamsters, and humans (Dai and Yu 1998; Yu et al. 1994, 1995a, 1995b, 

1996, 1997). The models assume that dissolution rates, as well as transverse breakage rates and patterns 

(i.e., breakage of long fibers into shorter ones), are the same in animals and humans. The models predict 

that for refractory ceramic fiber size ranges and concentrations encountered in workplaces, (1) mouthbreathing leads to higher fractional deposition of inhaled fibers than nose-breathing in humans; 

(2) fractional deposition of inhaled fibers is less in rats and hamsters than in nose-breathing humans; 

(3) humans have 1–2.5 times less deposited fiber per unit alveolar surface area than rats and hamster; and 

(4) size dimensions (length and width) of fibers deposited in human lungs are larger than those of fibers 

deposited in lungs of rats and hamsters (Yu et al. 1995a). 
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The rat model has been extended to other synthetic vitreous fibers (i.e., several types of insulation wools), 

but, to date, the human model has not. As discussed in the previous section, development of human 

models for insulation wools will decrease uncertainty in extrapolating from chronic inhalation data for 

pulmonary inflammation in rats and facilitate in the derivation of intermediate- and chronic-duration 

inhalation MRLs for these materials. 

There are no comparative toxicokinetic studies in humans or animals following oral or dermal exposure. 

Absorption and retention in the gastrointestinal tract and the skin are expected to be negligible in animals 

and humans. No data needs are identified at this time for comparative toxicokinetic data for these routes 

of exposure. 

Methods for Reducing Toxic Effects. Information specific to synthetic vitreous fibers regarding 

treatment of acute irritation effects or possible chronic effects from exposure or reduction of body 

burdens have not been identified, although minimizing exposure, wearing protective clothing, and rinsing 

of exposed areas (e.g., skin and eyes) with water are recommended (Ellenhorn et al. 1997; Goldfrank et 

al. 1998; Jeffress 1999; Mentzer 1999; OSHA 1999). 

As discussed in Section 3.5.1, the dose of fibers retained in the lower lung is a key determinant of the 

potential for fibers to induce toxic effects such as pulmonary inflammation, pulmonary fibrosis, lung 

cancer, or mesothelioma. Lung retention of fibers is the net result of lung deposition and clearance 

mechanisms including direct mucociliary clearance, macrophage-mediated clearance, dissolution rates, 

and transverse breakage of long fibers into shorter fibers. Once fibers are inhaled and deposited in the 

lung, there are no known treatment options to enhance the natural clearance mechanisms and reduce body 

burden after exposure. Additional research on physiological and molecular details of clearance 

mechanisms and mechanisms governing translocation into pleural tissue may provide clues for 

developing treatments to enhance clearance of the more biopersistent synthetic vitreous fibers from the 

lower lung and pleural tissue. 

Observed correlations between toxic potencies and dissolution rates for various types of vitreous and 

mineral fibers indicate that the dissolution of fibers in lung fluid is a key determinant of potential toxicity 

that is influenced by chemical composition and structure and manufacturing processes (Bernstein et al. 

2001a, 2001b; Eastes and Hadley 1996; Eastes et al. 2000; Hesterberg et al. 1998a; Hesterberg and Hart 

2001; Wardenbach et al. 2000). Ongoing research to develop new synthetic vitreous fibers that are less 
 

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biopersistent holds promise as a method to avert or decrease the potential for producing toxic effects. For 

example, vitreous fibers with relatively high alumina and silica contents have been shown to favor a 

relatively uniform, slower rate of dissolution, but increasing content of oxides of calcium, magnesium, 

and potassium can lead to nonuniform rates of dissolution, faster breakage, and faster clearance (Eastes et 

al. 2000; Hesterberg and Hart 2001; Morgan 1994b; Potter and Mattson 1991). 

As briefly discussed in Section 3.5.2, cellular and molecular events involved in fiber-induced 

nonneoplastic and neoplastic effect are poorly understood, but mechanistic studies (predominately with 

asbestos fibers) indicate that fibers retained in lung or pleural tissue may lead to cytotoxic and 

cytoproliferative changes as a result of increased production of reactive oxygen species that can damage 

cellular macromolecules, lead to cytotoxicity, and stimulate the release of inflammatory mediators, 

cytokines, and growth hormones (Churg et al. 2000; Driscoll 1996; IARC Expert Panel 1996). Several 

other mechanisms also have been proposed. Additional research on mechanisms of fiber-induced toxicity 

may eventually lead to the development of therapeutic approaches for reducing toxic effects from the 

biopersistent synthetic vitreous fibers or more efficient screening methods to evaluate the potential 

toxicities of newly developed synthetic vitreous fibers. 

Children’s Susceptibility. No information was located specifically concerning health effects in 

children exposed to synthetic vitreous fibers, and no studies were located that have compared immature 

and mature animals with respect to pharmacokinetics of, or susceptibility to, inorganic fibers of any type 

(including asbestos) by any route of exposure. There is no indication from the available literature that the 

pulmonary clearance mechanism might be less active or underdeveloped in children relative to adults. 

Direct effects on the developing fetus are not expected given the low absorption of synthetic vitreous 

fibers by the lung, gastrointestinal tract, and skin. Thus, there does not appear to be a need to conduct 

developmental toxicity tests for synthetic vitreous fibers. Additional research comparing pulmonary and 

pleural responses of immature and mature animals to the more biopersistent synthetic vitreous fibers may 

provide relevant information regarding the relative susceptibility of adults and children to the potential 

toxicity of synthetic vitreous fibers. Such experiments may be difficult to perform with immature 

animals, however, given the stress experienced by animals when they are fitted with nose-only inhalation 

apparatus (McConnell 1999). 

Child health data needs relating to exposure are discussed in Section 6.8.1 Identification of Data Needs: 

Exposures of Children. 
SYNTHETIC VITREOUS FIBERS 161 

3. HEALTH EFFECTS 

3.12.3 Ongoing Studies 

Ongoing studies funded solely by the U.S. government have not been identified. Other organizations 

have funded several large ongoing epidemiological studies of synthetic vitreous fiber manufacturing 

workers and the recent extensive animal toxicology studies reported in the published literature (see 

Section 3.2). 

 

 

SYNTHETIC VITREOUS FIBERS 163 

4. CHEMICAL AND PHYSICAL INFORMATION 

4.1 CHEMICAL IDENTITY 

Synthetic vitreous fibers are inorganic substances, largely composed of aluminum and calcium silicates 

that are derived from rock, clay, slag, or glass (IARC 1988, 2002). While naturally occurring mineral 

fibers such as asbestos are crystalline in structure, synthetic vitreous fibers are amorphous materials. 

There are several methods of categorizing synthetic vitreous fibers based either on origin, chemical 

structure, morphology, application, or method of manufacturing. The most recent classification scheme 

proposed by the International Agency for Research on Cancer (IARC) has divided these compounds into 

two broad classes: filaments and wools. The filaments contain continuous glass filaments, while the 

wools contain glass wool, rock (stone) wool, slag wool, refractory ceramic fibers, and other newly 

engineered biosoluble fibers (IARC 2002). Glass wools are further subdivided into insulation wools and 

special purpose wools (see Figure 2-1). Continuous filament products are produced by drawing or 

spinning the molten mix from nozzles, while the wools are manufactured with a rotary or centrifugal 

process without using a nozzle (see Chapter 5 for details). Generally, the wool fibers tend to be shorter 

and finer than the continuous filament fibers, and their diameters may be more variable (IARC 1988). 

The typical chemical composition of these types of synthetic vitreous fibers is represented in Table 4-1. 

Special purpose glass fibers are sometimes used in high technology industries and have very specific 

properties that are tailored to their specific use. Although the procedures used to make these fibers are 

similar to those of glass wool, the operating parameters are usually adjusted to create products with 

extremely small diameters. One example of a special purpose glass fiber is included in Table 4-1. 

Fibrous glass products are derived from powdered sand and largely consist of silicon and aluminum 

oxides. The final properties of the glass are dictated by the percent composition of other oxides including 

alkali metal oxides, alkaline earth oxides, and metal oxides like ZrO2 and Fe2O3. Glass, like other 

insulating materials, provides a high resistance to the passage of electricity. Electrical glass (E-glass) is a 

continuous filament type of fibrous glass developed for electrical applications that has excellent heat and 

water resistance (IARC 1988, 2002). The high resistivity of E-glass is related to its low alkali oxide 

content. The majority of continuous filament fibrous glass produced is E-glass (IARC 1988, 2002). 

Other types of glass are used for certain types of specialized purposes, and relatively small changes in the 
 

 

 

 

 

 

 

 

 

 

 

 

SYNTHETIC VITREOUS FIBERS 164 

4. CHEMICAL AND PHYSICAL INFORMATION 

Table 4-1. Chemical Identity of Some Types of Synthetic Vitreous Fibersa,b 

Rock wool Rock wool from Special 

Percent from basalt basalt and other Slag wool purpose glass 

com- E- S- AR- Glass melted in a material melted melted in RCF fiber 475 

position Glass Glass Glass wool furnace in a cupola a cupola RCF kaolin zirconia formulationc 

SiO2 52–56 65 60.7 55–70 45–48 41–53 38–52 49.5–53.5 47.5–50 57–58 

Al2O3 12–16 25 0–7 12–13.5 6–14 5–15 43.5–47 35–36 5–6 

B2O3 5–10 3–12 10–11 

K2O 0–2 2 0–2.5 0.8–2 0.5–2 0.3–2 <0.01 <0.01 2–3 

Na2O 0–2 13–18 2.5–3.3 1.1–3.5 0–1 0.5 <0.3 10–11 

MgO 0–5 10 0–5 8–10 6–16 4–14 <0.1 0.01 0–0.5 

CaO 16–25 5–13 10–12 10–25 20–43 <0.1 <0.05 2–3 

TiO2 0–1.5 0–0.5 2.5–3 0.9–3.5 0.3–1 2 0.04 0–0.1 

Fe2O3 0–0.8 0.1–0.5 1 <0.05 0–0.1 

FeO 11–12 3–8 0–2 

Li2O 1.3 0–0.5 

SO3 0–0.5 

S 0–0.2 0–0.2 0–2 

F2 0–1 0–1.5 

BaO 0–3 5 

ZrO2 21.5 0.1 15–17 

P2O5 0–0.5 

Cr2O3 <0.03 <0.01 

ZnO 4 

a

Navy Environmental Health Center 1997; TIMA 1993 

b

As is standard practice, the chemical composition of the elements are reported as oxides, even though no such individual crystals 

exist in the fibers. 

c

There are several formulations applicable to this category and formulation 475 is generally representative. 

AR-glass = alkali resistant glass; E-glass = electrical glass (so called because the low alkali oxide content makes it useful for 

electrical applications); RCF = refractory ceramic fiber; S-glass = high tensile strength glass (stronger than E-glass) 
SYNTHETIC VITREOUS FIBERS 165 

4. CHEMICAL AND PHYSICAL INFORMATION 

chemical composition of the glass can result in significant changes to its optical, electrical, chemical, and 

mechanical properties. Chemical glass (C-glass) is highly resistant to attack by chemicals such as 

hydrofluoric acid, concentrated phosphoric acid (when hot), and superheated water. The chemical 

resistance is determined by the relative amounts of the acidic oxides (SiO2, B2O3), basic oxides (CaO, 

MgO, Na2O, K2O), and amphoteric oxides (Al2O3). High-strength glass (S-glass) is almost completely 

composed of aluminum, silicon, and magnesium oxides and finds use in sophisticated high technology 

applications where high tensile strength is required; its tensile strength is typically 30–40% greater than 

E-glass. Alkali resistant glass (AR-glass) contains a high percentage of zirconium oxide, which makes 

this type of glass highly resistant to acidic and alkaline compounds. 

The term mineral wool is often used to collectively refer to rock wool and slag wool, although 

occasionally, glass wool was included in this category. Similar to other glass fibers, the chemical 

composition of rock wool and slag wool are primarily aluminum and silicon oxides. However, these 

wools possess a higher alkaline earth oxide content (MgO and CaO) and lower alkali metal oxide content 

(Na2O and K2O) than glass wool. Rock wool is derived from igneous rocks such as diabase, basalt, or 

olivine, while slag wool is derived from blast furnace slag from the steel industry (Navy Environmental 

Health Center 1997). 

Refractory ceramic fibers are a specialized type of synthetic vitreous fiber that are highly heat resistant 

and thus find use in high-temperature applications. Refractory ceramic fibers contain a much higher 

concentration of alumina than the other fibers listed in Table 4-1 and are sometimes referred to as 

aluminosilicate glasses. Although refractory ceramic fibers are amorphous at low temperatures, they 

undergo partial crystallization (devitrification) to quartz, cristobalite, or tridymite at elevated temperatures 

(Maxim et al. 1999b). 

4.2 PHYSICAL AND CHEMICAL PROPERTIES 

The important physical properties that are pertinent for organic compounds are generally not applicable to 

inorganic materials like fibrous glass. Properties such as vapor pressure, Henry’s law constant, and 

octanol/water partition coefficient are exceedingly low and not measurable. Even properties like melting 

point are difficult to define since fibrous glass products are amorphous and do not experience a distinct 

melting point as crystalline materials do, but soften over a fairly broad temperature range. The term 

softening point is used for materials that do not possess a definite melting point and is often employed 
SYNTHETIC VITREOUS FIBERS 166 

4. CHEMICAL AND PHYSICAL INFORMATION 

when discussing synthetic vitreous fibers. It represents the temperature at which plastic flow becomes 

viscous flow, and is specifically defined as the temperature at which the viscosity of the partial molten 

glass is 107.6 poise (TIMA 1993). Since synthetic vitreous fibers are often used in textile products as a 

reinforcing material, the softening point is an important physical property. Some physical properties of 

the synthetic vitreous fibers listed in Table 4-1 are shown in Table 4-2. Since the final products within 

each class of fibers can be varied according to manufacturing specifications, the values listed in Table 4-2 

should only be considered representative of the properties for each class in a very general sense. 

Synthetic vitreous fibers are not actually soluble in water, but the term dissolution is often used to 

describe the durability of synthetic vitreous fibers, especially as it pertains to biological fluid. This 

should not be confused with solubility, which is the amount of material that dissolves in solution before it 

reaches chemical equilibrium. The dissolution rate is the rate at which a fiber reacts with a solution and is 

degraded in it. Under alkaline and acidic conditions, the silicate network of synthetic vitreous fibers can 

be attacked, resulting in the leaching of individual ions and the eventual disruption of the entire fiber 

network. Due to the larger surface area, fine fibers have greater dissolution rates than course fibers (see 

Section 3.4 for details). 

Because the toxicity of fibers is related to their physical dimensions, it is important to characterize the 

size of synthetic vitreous fibers. In a typical glass fiber product, the average length is usually on the order 

of several centimeters, but the average diameter is usually on the order of a few microns. The nominal 

diameter is defined as the average fiber diameter in the finished product and varies according to fiber 

type, use, and manufacturing process involved (ACGIH 2001). The diameters of airborne fibers are an 

important physical property from a biological standpoint because thin fibers are considered respirable and 

may be deposited in the peripheral lung airways. Airborne fibers with diameters <3 μm are generally 

considered respirable in humans. There is also a strong correlation between the fiber diameter and the 

airborne fiber levels found in workplaces (Esmen and Erdal 1990; Esmen et al. 1979a, 1979b). Generally, 

the greater the fiber diameter, the lower the airborne fiber concentration. The nominal fiber diameter of 

continuous filament fibrous glass is usually in the range of 3–25 μm, depending upon the application, 

with typical diameters in the range of 6–15 μm (Navy Environmental Health Center 1997). The method 

of producing continuous filament fibers allows for excellent control of the preset fiber diameter and as a 

result, there is little variation in range of diameters for the resulting product. The production of rock 

wool, slag wool, and glass wool includes a rotary or centrifugal process resulting in nominal fiber 
 

SYNTHETIC VITREOUS FIBERS 167 

4. CHEMICAL AND PHYSICAL INFORMATION 

Table 4-2. Physical Properties of Some Types of Synthetic Vitreous Fibersa 

Refractory Special purpose 

Property E-Glass S-Glass 

ARGlass Glass 

wool 

Rock 

wool 

Slag 

wool 

ceramic 

fibers 

glass fiber 475 

formulationb 

Molecular N/A N/A N/A N/A N/A N/A N/A N/A 

weight 

Density (g/cm3

) 2.60– 2.5 2.52 2.40– 2.7–2.9 2.7–2.9 2.6–2.7 2.4 

2.65 2.55 

Softening point 835– 970 680 650– No data No data 1,740–1,800 650 

°C 860 700 

Dielectric 5.8–6.4c

 4.9–5.3c No No data No data No data No data No data 

constant at data 

1 MHz 

Modulus of 70–75 85 70–75 55–62 55–62 48–76 76–100d

 No data 

elasticity (GPa) 

Refractive 1.55– 1.52 1.525 1.51– 1.6–1.8 1.6–1.8 1.55–1.57 1.53 

index 1.57 1.54 

Tensile 

strength (MPa) 

3,400c

 4,590c 3,700c No data 482–689d 482– 

689d 

1,000– 

1,300c,e 

No data 

a

All data derived from TIMA 1993 unless otherwise noted. 

b

There are several formulations applicable to this category and formulation 475 is generally representative. c

Fitzer et al. 1988 

d

Navy Environmental Health Center 1997
 e

There are various commercial products of boron or silicon carbide filaments or yarns with high tensile strength, but 

these are crystalline fibers and technically not synthetic vitreous fibers. 

N/A = not applicable 
SYNTHETIC VITREOUS FIBERS 168 

4. CHEMICAL AND PHYSICAL INFORMATION 

diameters in the range of about 3–7 μm for rock wool and slag wool and 3–15 μm for ordinary glass wool 

(Navy Environmental Health Center 1997). The smaller diameters of these fibers in comparison to 

continuous filament fibers, allows for the possibility that a small fraction of these fibers may be respirable 

when they become airborne. Special purpose glass fibers are produced by a flame attenuation process 

whereby the hot, molten glass is poured in front of a high temperature gas flame, resulting in fibers with a 

mean diameter of <3 μm and very often <1 μm. Refractory ceramic fibers (RCFs) are produced by 

melting and spinning or blowing of calcinated kaolin, aluminum silicates and metallic oxide blends, and 

high purity aluminum silicate. The typical fiber diameter of RCFs is 1–5 μm. 

Christensen et al. (1993) employed light microscopy (LM) and scanning electron microscopy (SEM) to 

measure the length-weighted diameters of 22 synthetic vitreous fiber products obtained from 11 different 

manufacturers. In this study, nine different glass wool products, nine rock wool or slag wool products, 

three refractory ceramics, and a single special purpose glass fiber were analyzed. The results of this study 

are summarized in Table 4-3. 

The results of a recent comprehensive workplace monitoring study using transmission electron 

microscopy (TEM) was reported by Mast et al. (2000), which characterized the airborne fiber dimensions 

of refractory ceramic fibers. Measurements of 3,357 fibers obtained at 98 workplaces yielded an airborne 

diameter range of 0.067–4.0 μm. The arithmetic mean and standard deviation were reported as 1.05 μm 

and 0.64 μm, respectively, while the geometric mean and standard deviation were reported as 0.84 μm 

and 2.05 (the geometric standard deviation is unitless), respectively (Mast et al. 2000). Fiber lengths 

ranged from 0.6 to 138 μm, with an arithmetic mean length and standard deviation of 20.6 μm and 

19.3 μm, respectively. The geometric mean length and geometric standard deviation were reported as 

14.1 μm and 2.48, respectively. The size distributions of airborne synthetic vitreous fibers at different 

locations under a variety of occupational settings were summarized in the most recent IARC monograph 

(IARC 2002) and these data are condensed in Table 4-4. 
 

SYNTHETIC VITREOUS FIBERS 169 

4. CHEMICAL AND PHYSICAL INFORMATION 

Table 4-3. Measured Diameters of Glass Wool, Rock Wool, Slag Wool, Refractory
 

Ceramic Fibers, and a Special Purpose Glass Fibera
 

Number of 

products 

studied 

Arithmetic mean 

diameter range 

(μm) LM 

Geometric mean 

diameter range 

(μm) LM 

Arithmetic mean 

diameter range 

(μm) SEM 

Geometric mean 

diameter range (μm) 

SEM 

Glass wool 

9 2.4–8.1 1.7–6.6 1.2–7.7 0.8–6.3 

Special purpose glass fiberb 

1 Not applicableb

Mineral wool 

 Not applicableb

 0.6 0.4 

9 2.5–4.7 1.7–3.3 2.4–5.3 1.7–4.0 

Refractory ceramic fibers 

3 2.3–3.9 1.5–2.8 2.4–3.8 1.7–2.8 

a

Data obtained from Christensen et al. (1993); for all samples, between 400 and 490 individual fibers were
 

measured in order to derive the statistical quantities presented in the table. b

A single special purpose glass wool fiber was studied with a diameter too small to be accurately measured by LM. 

LM = light microscopy; SEM = scanning electron microscopy
 
 

SYNTHETIC VITREOUS FIBERS 170 

4. CHEMICAL AND PHYSICAL INFORMATION 

Table 4-4. Statistical Analysis of Airborne Fibers Under Different Occupational 

Settingsa
 

GM diameter GSD GM length GSD Length-diameter 

SVF product or setting (μm) diameter (μm) length correlation 

Rock wool production 0.3–0.5 1.9–2.7 7.0–9.0 2.2–3.0 0.4–0.6 

Rock wool use 1.2 2.7 22 4.0 0.7 

Glass wool use 0.75 2.8 16 3.5 0.7 

Glass wool use 0.8–1.9 1.4–1.9 9.5–30 1.4–2.5 0.2–0.7 

Rock wool use 1.6–1.9 1.6–1.9 19 1.7–2.7 0.4–0.6 

Glass wool house 0.91–1.2 1.7–1.8 9.2–9.3 2.3–2.5 No data 

prefabrication 

Rock wool house prefabrication 1.3–1.7 1.9 12–17 2.5–2.8 No data 

Installation of SVF batts 0.9–1.3 2.2 22–37 2.8–2.9 0.5–0.6 

Installation of loose SVF with 1.0–2.0 1.8–2.2 30–50 2.3–2.6 0.4–0.6 

binder 

Installation of loose SVF 0.60 1.9 14–15 2.4–2.6 0.5–0.6 

without binder 

RCF production and use 0.84 2.05 14.1 2.5 0.4 

RCF factory 0.96–1.2 1.7–1.9 12–19 2.4–2.6 No data 

RCF factory 0.86 1.9–2.0 11–13 2.4–2.6 No data 

a

IARC 2002 

GM = geometric mean; GSD = geometric standard deviation; RCF = refractory ceramic fiber; SVF = synthetic 

vitreous fiber 
 

SYNTHETIC VITREOUS FIBERS 171 

5. PRODUCTION, IMPORT/EXPORT, USE, AND DISPOSAL 

5.1 PRODUCTION 

Synthetic vitreous fibers are unlike common minerals because they are amorphous and do not occur 

naturally in the environment. Fibrous glass and glass wool are made by melting sand in combination with 

other oxides such as lime or soda without crystallizing them. Rock wool is derived from igneous rock 

containing high levels of calcium, while slag wool is produced from the by-products of metal smelting. 

Although rock wool and slag wool were being produced in Europe in the mid to late 19th century, it was 

not until after World War I that its production within the United States became significant (IARC 1988). 

In 1928, there were 8 manufacturing plants in the United States that produced rock wool or slag wool, by 

1939, the number had grown to 25, and in 1985, there were 58 facilities in the United States producing 

fibrous glass, mineral wool, and refractory ceramics (IARC 1988). 

Historical U.S. production volumes for synthetic vitreous fibers are shown in Tables 5-1 and 5-2. Glass 

wool products comprise the vast majority of synthetic vitreous fibers produced in the United States. The 

Glass Manufacturing Industry Council (GMIC) reports that there are currently 10 major manufacturers 

operating about 40 plants around the United States, and estimates that the current production volume of 

glass fibers, including glass wool, is about 3 million tons (2.72x109

 kg) annually (GMIC 2002). The 

annual U.S. production of mineral wool is roughly 550,250 tons (5.0x108 kg), and accounts for 

approximately 10–15% of the total amount of synthetic vitreous fibers produced. The total domestic 

production of refractory ceramic fibers was approximately 107.7 million pounds (4.9x107

 kg) in 

1997 (Mast et al. 2000). For comparison, the total production volume of all synthetic vitreous fibers in 

Canada was estimated as 250–300 kilotons (2.26x108

–2.71x108 kg) in 1991, of which 70% was glass 

wool, 20% was mineral wool, 10% was continuous filament glass, and <1% was refractory ceramic fibers 

(Environment Canada 1993). 

The production of fibrous glass differs depending upon whether the final product being formed is 

continuous filament glass fibers or glass wool. In general, a glass-making furnace is used to melt the raw 

materials and a separate device is frequently used to convert the melt into marbles. The preformed 

marbles can be stored, distributed, and remelted for fiber formation. A direct melt process is also 
 

 

SYNTHETIC VITREOUS FIBERS 172 

5. PRODUCTION, IMPORT/EXPORT, USE, AND DISPOSAL 

Table 5-1. Production Volumes of Glass Wool, Rock Wool, and Slag Wool 

Products in the United Statesa
 

Product Quantity (million kg), 1977 Quantity (million kg), 1982 

Wool for insulation (homes and commercial/industrial buildings) 

Loose and granulated fiber 373.2 327.2 

Building batts, blankets, and rolls 359.9 (R-19 or more)b 530.0 (R-19 or more)b 

403.9 (R-11 to R-18.9) 418.4 (R-11 to R-18.9) 

Not available (R-10.9 or less) 52.3 (R-10.9 or less) 

Acoustical, such as wall and ceiling Not available 46.3 

Wool for industrial, equipment, and appliance insulationc 

Flexible blankets, rolls, and batts (plain) 167.8 173.2 

Flexible blankets, rolls, and batts 16.5 21.4 

(coated) 

Flexible blankets, rolls, and batts (faced) 24.0 Not available 

Special purpose insulation 19.6 11.5 

Blocks and boards 46.0 10.0 

 Pipe insulation 30.5 26.8 

Acoustical, including pads, boards, and 24 Not available 

patches 

a

IARC 1988 

b

The R-value is the reciprocal of the amount of heat energy per area of material per degree difference between the 

outside and inside. 

c

Includes amounts from products produced in the same establishment as well as products purchased or transferred 

from other establishments. 
SYNTHETIC VITREOUS FIBERS 173 

5. PRODUCTION, IMPORT/EXPORT, USE, AND DISPOSAL 

Table 5-2. Continuous Filament Glass Fiber Production in the United Statesa 

Year Quantity (million kg) 

1975 247.88 

1976 306.90 

1977 357.30 

1978 419.04 

1979 460.36 

1980 393.62 

1981 472.61 

1982 408.15 

1983 530.27 

1984 632.88 

a

IARC 1988 
SYNTHETIC VITREOUS FIBERS 174 

5. PRODUCTION, IMPORT/EXPORT, USE, AND DISPOSAL 

employed, which produces the fibers while avoiding the conversion of the melt into marbles. In the 

production of continuous filament fibers, nozzles are attached to the bushings on the furnace forehearth, 

and mechanical drawing is used to form the fibers from the melt. A fine mist of water is sprayed onto the 

strands as they are extruded through the bushing and a lubricating agent is applied before the strands are 

wound into a cake (IARC 1988). 

Glass wool and mineral wool are manufactured with a rotary or centrifugal process without the use of 

nozzle extruders. In this process, the molten material from the furnace is transferred into a rotating 

spinner, and the fibers are produced as centrifugal force extrudes the material through small holes in the 

side of the spinning device. The final wool fibers are generally shorter and thinner than continuous 

filament fibers. Sometimes, a blowing process in which the melt is forced through the bushings at the 

bottom of the crucible by a downward directed stream of gas is used to extrude the fibers (Fitzer et al. 

1988). The resultant fiber strands are usually about 3–6 μm in diameter and about 3–10 cm in length 

(Fitzer et al. 1988). Prior to converting the fibers to final products, binders, sizings, or lubricants are 

usually added. Binders are phenol-formaldehyde resins that impart structural rigidity to the fiber. 

Lubricating oils or paraffin oils are added to reduce dust and lint formation of the final product and reduce 

the amount of airborne fibers during their use. Sizings are added to promote adhesion between fibers and 

the matrix material in reinforced applications. Several sizings are used, including polyvinyl acetate 

chrome mixture, polyvinyl acetate silane, and epoxy silane (Navy Environmental Health Center 1997). 

Special purpose glass fibers are usually produced with a flame attenuation process, which results in the 

production of very small diameter fibers. The flame attenuation method of producing fibers is a two-step 

procedure TIMA 1993). In the first step, the melt is drawn through the bushings of the furnace to produce 

strands of course fibers. The course fibers are then remelted and attenuated into several finer fibers with a 

high temperature gas flame, normally impinging at right angles to the primary fiber. Fibers are usually 

propelled by high velocity gasses through a forming tube, upon which a binder is sprayed, before 

producing the final wool fiber (TIMA 1993). 

Refractory ceramic fibers are produced by blowing and spinning processes similar to those used in the 

production of wool, but the starting material is kaolin clay rather than rock or slag (IARC 1988). Since 

refractory fibers are relatively new materials, the exact processes used for producing these individual 

fibers are often considered proprietary and are not disclosed (Fitzer et al. 1988). 
SYNTHETIC VITREOUS FIBERS 175 

5. PRODUCTION, IMPORT/EXPORT, USE, AND DISPOSAL 

5.2 IMPORT/EXPORT 

Data regarding the quantities of manmade glass filaments (including glass wool), mineral wool, and 

refractory ceramic goods imported and exported to and from the United States from 1998 to 2001 are 

summarized in Table 5-3 (USDOC 2002). 

5.3 USE 

Synthetic vitreous fibers are an important substitute for asbestos in a variety of products where thermal, 

acoustical, and electrical resistance is required. Fibrous glass (including glass wool) accounts for about 

80% of the production of synthetic vitreous fibers in the United States (WHO 1988). The majority of this 

production is in the form of glass wool, which is used for insulation purposes, similar to the mineral 

wools. Continuous filament fibers are used as reinforcement in plastics and building products, and in 

industrial fabrics (ACGIH 2001). Mineral wool accounts for about 10–15% of the production of 

synthetic vitreous fibers in the United States (WHO 1988). Similar to glass wool, the vast majority of 

rock wool and slag wool is produced for thermal and acoustical insulation applications for construction of 

homes, buildings, and other structures (IARC 1988). Appliances and plumbing applications also use 

glass wool and mineral wool for insulation purposes. The end products are usually in the form of bats, 

boards, blankets, and sheets. Refractory ceramics fibers and special purpose fibers only account for about 

2% of all synthetic vitreous fibers produced in the United States (WHO 1988). Refractory ceramic 

materials are very heat resistant and find use in applications that require high temperatures. Final 

products are often in the form of blankets, boards, felts, bulk fibers, and paper and textile products (IARC 

1988). Refractory ceramic blankets or boards are often used as insulation in ships and in firewalls to 

contain fires or in catalytic converters in the automobile industry and in aircraft and aerospace engines 

(IARC 1988). Ceramic blankets and boards are commonly used as linings for furnaces and kilns. 

Ceramic fiber textile products such as yarns or fabrics find use in flame resistant clothing, curtains, and 

other materials. Specialty purpose glass fibers are very expensive to manufacture and only find use in 

high technology applications such as high performance insulation in the aircraft industry and specialty 

filtration products (WHO 1988). 
SYNTHETIC VITREOUS FIBERS 176 

5. PRODUCTION, IMPORT/EXPORT, USE, AND DISPOSAL 

Table 5-3. U.S. Import/Export Volume of Glass Fibers (Including Glass Wool), 

Mineral Wool and Refractory Ceramic Goodsa
 

Year Import quantity (kg) Export quantity (kg) 

Glass fibers including glass wool 

1998 73,074,090 119,386,619 

1999 96,924,030 112,438,061 

2000 103,001,680 119,829,077 

2001 93,045,850 122,598,785 

Mineral wool 

1998 4,096,373 13,507,235 

1999 4,732,083 12,856,177 

2000 5,086,956 15,736,857 

2001 4,330,133 15,760,666 

Refractory ceramic goods 

1998 26,677,254 21,567,397 

1999 23,552,712 11,044,364 

2000 28,520,534 16,464,014 

2001 24,191,899 12,054,960 

a

USDOC 2002 
SYNTHETIC VITREOUS FIBERS 177 

5. PRODUCTION, IMPORT/EXPORT, USE, AND DISPOSAL 

5.4 DISPOSAL 

No components in synthetic vitreous fibers are identified by the EPA as hazardous waste in Resource 

Conservation and Recovery Act (RCRA) (40CFR Part 261), and as such they may be disposed of in 

landfills; however, state and local regulations may apply. Provided that refractory ceramic fibers and 

other synthetic vitreous fibers have an average diameter >1 μm, the EPA agrees that these substances 

would not fall within the fine mineral fibers category under Comprehensive Environmental Response, 

Compensation and Liability Act (CERCLA) and, thus, would not be subject to release reporting and 

liability requirements. Should synthetic vitreous fibers, however, have an average diameter of ≤1 μm, 

these substances would be considered hazardous substances and, therefore, would be subject to CERCLA 

requirements (EPA 1995). The U.S. Navy suggest that all synthetic vitreous fiber material be wetted 

before placing the material in heavy duty plastic bags or other impermeable objects before being 

discarded at landfills (Navy Environmental Health Center 1997). 

Glass and insulating material are often recycled for further use after being removed or discarded. 

According to the North American Insulation Manufacturers Association (NAIMA), over 18 billion 

pounds of glass and insulating material have been recycled in North America since 1992 (NAIMA 2002). 

 

 

SYNTHETIC VITREOUS FIBERS 179 

6. POTENTIAL FOR HUMAN EXPOSURE 

6.1 OVERVIEW 

Synthetic vitreous fibers were not identified in any of the 1,647 hazardous waste sites that have been 

proposed for inclusion on the EPA National Priorities List (NPL) (HazDat 2004). However, the number 

of sites evaluated for synthetic vitreous fibers is not known. The frequency of these sites can be seen in 

Figure 6-1. 

Like other inorganic substances, synthetic vitreous fibers do not undergo typical transformations in the 

environment, such as photolysis and biodegradation, which are important for organic compounds. Under 

acidic or alkaline conditions, synthetic vitreous fibers may undergo dissolution, whereby the silicate 

network may be attacked and slowly degraded. Experimental dissolution rates of tested fibers have been 

reported to span over 5 orders of magnitude. This degradation mechanism is more relevant in biological 

systems than it is in the environment (see Section 3.4 for more details). The transport and partitioning of 

synthetic vitreous fibers are largely governed by their size. Large fibers are removed from air and water 

by gravitational settling at a rate dependent upon their size, but small fibers may remain suspended for 

long periods of time. 

The general population can be exposed to low levels of synthetic vitreous fibers when insulating material 

or other synthetic vitreous fiber-containing material such as ceiling boards are physically disturbed and 

fibers become suspended in the air. Home, building, and appliance insulation are often composed of glass 

wool, rock wool, or slag wool, and low levels of synthetic vitreous fibers have been detected in indoor air. 

These levels are usually on the order of about 1x10-4 fiber/cc, although higher levels are often observed 

during the installation of insulation in attics or ceilings; however, these levels quickly return to preinstallation levels, usually in 1 or 2 days. Low levels of synthetic vitreous fibers have also been detected 

in outdoor air, and available data suggest that there are little differences in the concentration of these 

fibers near source dominated areas (e.g., near production plants) when compared to other locations. 

Typical levels of synthetic vitreous fibers in outdoor ambient air can vary, but are also on the order of 

about 1x10-4 fiber/cc. 
SYNTHETIC VITREOUS FIBERS 180 

6. POTENTIAL FOR HUMAN EXPOSURE 

Figure 6-1. Frequency of NPL Sites with Synthetic Vitreous Fiber Contamination* 

Frequency of 

NPL Sites 

Derived from HazDat 2004 

*No data are available in HazDat 2004 
SYNTHETIC VITREOUS FIBERS 181 

6. POTENTIAL FOR HUMAN EXPOSURE 

The overwhelming majority of human exposure to synthetic vitreous fibers occurs as occupational 

exposure through inhalation and dermal contact. Occupational exposure is estimated to be several orders 

of magnitude greater than environmental exposure. Employees at manufacturing facilities where 

synthetic vitreous fiber products are produced, as well as workers who regularly install or come into 

contact with insulating material are most at risk for elevated levels of exposure. Workers involved in 

demolition work, as well as in building maintenance and repair, are potentially exposed to higher levels of 

synthetic vitreous fibers once these materials are disturbed or demolished. Workers involved in the 

removal of refractory ceramic fiber insulation in high temperature furnaces may also be exposed to 

quartz, cristobalite, and tridymite, which form as refractory ceramic fibers devitrify at elevated 

temperatures (Maxim et al. 1999b). 

In the literature discussing data on airborne synthetic vitreous fibers, total dust or total fiber levels are 

occasionally reported. These levels include all types of fibers, not just the synthetic vitreous fibers, and 

quite often synthetic vitreous fibers only constitute a small percentage of the total concentration of fibers 

in the sample. The precise definition of what constitutes an actual fiber, and how these fibers should be 

counted under microscopic examination is not standardized, and different studies have used different 

counting methods (see Chapter 7). A fiber is usually defined as having length of at least 5 μm, and a 

length to diameter ratio (aspect ratio) of either 5:1 or 3:1 (TIMA 1993). Frequently, only the levels of 

respirable fibers are reported. Respirable fibers are those fibers that can be inhaled into the lower lung 

and usually only fibers with diameters of <3 μm are considered respirable in humans (although some 

authors have used larger values in older publications). It is also generally accepted that fibers longer than 

200–250 μm are too large to be deposited in the lung, and are therefore not respirable (TIMA 1993). 

Recently, the American Conference of Governmental Industrial Hygienists (ACGIH) has defined 

respirable fibers as possessing a diameter <3 μm, length ≥5 μm, and an aspect ratio of ≥3:1 (ACGIH 

2001). The term respirable fiber in this chapter refers to fibers possessing diameters of <3 μm, unless 

otherwise noted. Section 3.4 (Toxicokinetics) discusses the deposition and clearance of fibers in the lung 

in more detail. 

Phase contrast microscopy (PCM) is most frequently used to measure fiber levels, but this method cannot 

detect fibers with diameters smaller than 0.25 μm. PCM uses visible light photons for analysis, and 

because the resolution of a microscope is a function of the wavelength of photons used for analysis and 

the numerical aperture of the microscope, the theoretical limit of 0.25 μm for light microscopy cannot be 
SYNTHETIC VITREOUS FIBERS 182 

6. POTENTIAL FOR HUMAN EXPOSURE 

improved upon. Transmission electron microscopy (TEM) or scanning electron microscopy (SEM) are 

often employed to improve sensitivity since these techniques can measure fibers with smaller diameters 

than PCM because electrons with much shorter wavelengths than visible photons are used in these 

experiments (see Chapter 7 for details). It is often difficult to directly compare results of early studies to 

more recent ones due to the methods in which fibers were sampled and analyzed. Many early monitoring 

studies employed a set of fiber counting rules specifying a fiber as a particle with length >5 μm and 

aspect ratio of ≥3:1 (counting rules A). More recent studies frequently use a counting rule in which fibers 

are counted if their lengths are >5 μm, their diameters are <3 μm, and their aspect ratio is ≥5:1 (counting 

rules B). While the differences in actual fiber counts are usually small, calculating fibers using counting 

rules A generally yield higher counts as compared to the counting rules B (Breysse et al. 1999; Miller et 

al. 1995). See Chapter 7 for more details regarding the analysis, sampling, and counting of fibers. 

The Toxics Release Inventory (TRI) has not listed synthetic vitreous fibers for inclusion in its database 

(TRI01 2003). 

6.2 RELEASES TO THE ENVIRONMENT 

Low levels of synthetic vitreous fibers may be released to the environment during their production or use. 

Demolishing buildings or houses that contain synthetic vitreous fibers in insulating products, ceiling 

boards etc., may also release low levels of synthetic vitreous fibers locally. The majority of releases most 

likely arise from the disposal of material containing synthetic vitreous fiber in landfills. 

6.2.1 Air 

Very limited data are available regarding the emission of synthetic vitreous fibers to ambient air. The 

concentration of synthetic vitreous fibers in air emissions from fibrous glass, rock wool, and slag wool 

plants in Germany were on the order of 0.01 fiber/cc, and the total fibrous dust emissions from these 

plants were estimated as 1.8 tons/year (WHO 1988). Concentrations of respirable fibers as high as 

2.7 fibers/cc were measured by PCM in stack gasses at several older glass, rock, and slag wool plants in 

the United States (Environment Canada 1993). Concentrations of total fibers in stack gasses measured in 

1991 using TEM at four refractory ceramic fiber production plants and three refractory ceramic fiber 

processing facilities ranged up to 14.1 fibers/cc (Environment Canada 1993). 
 

SYNTHETIC VITREOUS FIBERS 183 

6. POTENTIAL FOR HUMAN EXPOSURE 

Synthetic vitreous fibers were not identified in any of the current or former NPL hazardous waste sites 

(HazDat 2004). Synthetic vitreous fibers were not included in the TRI (TRI01 2003). 

6.2.2 Water 

Few data exist regarding the frequency or levels of synthetic vitreous fibers released to water. Glass 

fibers were identified in samples of sewage sludge from five cities in the United States; however, the 

specific form and exact quantity of the glass fibers were not reported (Bishop et al. 1985). 

Synthetic vitreous fibers were not identified in any of the current or former NPL hazardous waste sites 

(HazDat 2004). Synthetic vitreous fibers were not included in the TRI (TRI01 2003). 

6.2.3 Soil 

No data exist regarding the frequency or levels of synthetic vitreous fibers released to soil. Most of these 

releases are expected to be in the form of discarded construction material (e.g., insulation, ceiling boards, 

etc.) that have been disposed of at landfills. 

Synthetic vitreous fibers were not identified in any of the current or former NPL hazardous waste sites 

(HazDat 2004). Synthetic vitreous fibers were not included in the TRI (TRI01 2003). 

6.3 ENVIRONMENTAL FATE 

6.3.1 Transport and Partitioning 

The transport, distribution, and degradation of synthetic vitreous fibers in the environment have not been 

studied (WHO 1988). However, synthetic vitreous fibers are nonvolatile and generally insoluble, so their 

natural tendency is to settle out of air and water, and deposit in soil or sediment. 
SYNTHETIC VITREOUS FIBERS 184 

6. POTENTIAL FOR HUMAN EXPOSURE 

6.3.2 Transformation and Degradation 

6.3.2.1 Air 

Synthetic vitreous fibers are not known to undergo any significant transformation or degradation in air 

(WHO 1988). 

6.3.2.2 Water 

Synthetic vitreous fibers are not known to undergo any significant transformation or degradation in water 

(WHO 1988). The silicate network of all synthetic vitreous fibers can be attacked by acids or alkaline 

solutions, but this does not occur to any significant extent under environmentally relevant conditions. 

Using in vitro tests at 37 °C with simulated extracellular fluid (pH 7.4), the dissolution rates of glass, 

rock, and slag wools with diameters of 1 μm were reported as 0.4, 1.2, and 2.0 years, respectively 

(Environment Canada 1993). Lifetimes for refractory ceramic fibers were about 5 years. Because of their 

larger surface area, fine fibers will undergo dissolution more readily than course fibers (see Section 3.4 

for more details regarding dissolution in biological media). 

6.3.2.3 Sediment and Soil 

Synthetic vitreous fibers are not known to undergo any significant transformation or degradation in soil or 

sediment (WHO 1988). 

6.4 LEVELS MONITORED OR ESTIMATED IN THE ENVIRONMENT 

6.4.1 Air 

Available monitoring data suggest that the concentration of synthetic vitreous fibers in the atmosphere is 

very low. The levels of fibrous glass in ventilation systems and in the ambient air from various locations 

of California were studied from 1968 to 1971, in order to investigate the erosion of fibers from air 

transmission systems (Balzer et al. 1971; NIOSH 1976). The concentration of fibrous glass in 36 ambient 

air samples collected from Berkeley, San Jose, Sacramento, the Sierra Mountains, and Los Angeles 

ranged from not detected to 9.0x10-3 fiber/cc, with an arithmetic mean of 2.57x10-3 fiber/cc, as 
 

SYNTHETIC VITREOUS FIBERS 185 

6. POTENTIAL FOR HUMAN EXPOSURE 

determined by PCM and TEM (NIOSH 1976). The fiber diameters ranged from 0.10–17.7 μm, with an 

arithmetic mean of 4.3 μm. The concentration of fibrous glass in 37 ventilation system samples ranged 

from not detected to 2.0x10-3 fiber/cc (8.7x10-4 fiber/cc, arithmetic mean), and the fiber diameters were 

0.10–17.7 μm (3.7 μm, arithmetic mean). The mean airborne concentrations of fibers were monitored at 

one rural location and three cities in Germany in 1981–1982 (Hohr 1985). Samples were analyzed with 

TEM in conjunction with energy-dispersive x-ray analysis (EDXA), and electron diffraction analysis. 

The fibers identified as synthetic vitreous fibers constituted about 1–5% of the inorganic fibers, with a 

concentration range of 4.0x10-5–1.7x10-3 fiber/cc (Hohr 1985). The results of these, and several other 

past monitoring studies have been compiled and summarized in IARC (1988, 2002) and WHO (1988). 

The concentration of respirable glass fibers near a large fiberglass wool manufacturing facility in Newark, 

Ohio ranged from below the detection limit of 1.0x10-5 fiber/cc to 1.4x10-4 fiber/cc, during four sampling 

periods in 1988–1989 as determined by PCM (Switala et al. 1994). These levels were similar to the 

measured levels in ambient air from a rural site located 10 miles away from the plant in Granville, Ohio. 

The range of concentrations at the rural location was from below the detection limit of 1.0x10-5 fiber/cc to 

1.5x10-4 fiber/cc, during the same sampling period. Furthermore it was shown that only 16% of the 

460 samples obtained at the Newark (plant) location had concentrations of glass fibers above the 

detection limit and only 4% of the 485 samples obtained from the Granville (rural) location had 

concentrations above the detection limit. Glass fibers accounted for <1% of the total respirable fibers 

measured at these sites. The total respirable fiber concentrations (this includes all fibers, not just 

synthetic vitreous fibers) at the Newark location ranged from below the detection limits to 

0.02318 fiber/cc, while the levels of total respirable fibers at the Granville site ranged from below the 

detection limits to 0.04290 fiber/cc. The majority of non-glass fibers were reported to be pollen and 

trichome, seed hairs, and insect parts (Switala et al. 1994). Low levels of synthetic vitreous fibers in 

ambient air have also been measured in various locations in France (Gaudichet et al. 1989). The 

maximum concentration of respirable synthetic vitreous fibers in outdoor air at 18 locations in Paris was 

1.5x10-5 fiber/cc, with a mean value of 2.0x10-6 fiber/cc as determined by PCM (Gaudichet et al. 1989). 

In general, indoor air concentrations of synthetic vitreous fibers are very low under non-occupational 

settings, unless there is a disturbance in the fiberglass insulation system or ceiling boards of the home or 

building. A comprehensive study using PCM was carried out in Denmark in order to study the 

concentration of synthetic vitreous fibers in the indoor air of public buildings (Schneider et al. 1990). The 

concentration of respirable airborne synthetic vitreous fibers ranged from not detected to 
SYNTHETIC VITREOUS FIBERS 186 

6. POTENTIAL FOR HUMAN EXPOSURE 

1.66x10-3 fiber/cc in air samples collected from 105 rooms using 10 different types of ceiling boards. The 

mean respirable levels were in the range of 2.60x10-5–2.13x10-4 fiber/cc. The levels of nonsynthetic 

vitreous fibers were at least an order of magnitude greater than the levels of synthetic vitreous fibers. It 

was also reported that no respirable airborne levels of synthetic vitreous fibers were observed in 65 of the 

rooms, but that low levels of respirable synthetic vitreous fibers were found on other objects such as 

tables or cupboards (Schneider et al. 1990). The results of this study pertaining to the levels of airborne 

synthetic vitreous fibers are summarized in Table 6-1. 

A recent study employing both PCM and SEM analyzed 51 residential and commercial buildings 

throughout the United States, and found respirable synthetic vitreous fibers were present in only 2 of the 

50 samples analyzed by SEM (Carter et al. 1999). It was demonstrated that the majority of airborne fibers 

were organic, and that inorganic fibers, including synthetic vitreous fibers, composed <10% of the 

detectable respirable amount. Gaudichet et al. (1989) measured the levels of synthetic vitreous fibers at 

79 indoor locations in France where synthetic vitreous fiber materials were used in a variety of 

applications, and found the levels of respirable synthetic vitreous fibers to be low. A range of respirable 

synthetic vitreous fibers were reported as not detected to 6.23x10-3 fiber/cc with a median value of 

3.0x10-6 fiber/cc (Gaudichet et al. 1989). The levels of respirable fibers (diameter <3 μm and lengths 

>5 but <100 μm) were measured in 12 houses during the installation of rock wool or glass wool insulation 

material by PCM and TEM (Jaffrey 1990). Almost no differences were noticed in the pre-installation 

airborne levels, which were on the order of 1.0x10-4 fiber/cc, and the post insulation samples, which were 

taken 2 days after installation was complete. Comparable results were obtained by Miller et al. (1995) 

when analyzing the fiber concentrations in living spaces of 14 homes prior to installation of insulation and 

the evening following installation. Total fiber levels ranged from 0.0020 to 0.011 fiber/cc before 

installation, and from 0.0030 to 0.015 fiber/cc 1 day post-installation using PCM and counting rules A 

(see Chapter 7). Fiber concentrations calculated using counting rules B were slightly lower, but there 

were no statistically significant differences when comparing levels calculated by either the A or 

B counting rules. Similar results were obtained when using SEM methods and the two counting rules to 

measure only synthetic vitreous fibers levels, although the level of fibers classified as synthetic vitreous 

fibers were about an order of magnitude lower than the total fiber levels. The maximum pre-installation 

level of synthetic vitreous fibers was 0.001 fiber/cc, and the post-installation levels ranged from below the 

detection limit of 0.001 fiber/cc to 0.007 fiber/cc. 
SYNTHETIC VITREOUS FIBERS 187 

6. POTENTIAL FOR HUMAN EXPOSURE 

Table 6-1. Airborne Concentrations of Synthetic Vitreous Fibers in 

Buildings in Denmarka
 

Type of ceiling 

boardb 

Number 

of rooms 

Water soluble 

binder 

Respirable fiber level 

fibers/cc; range (mean) 

Non-respirable fiber level 

fibers/cc; range (mean) 

Karlit mineral 11 Yes 0–1.66x10-3 (2.13x10-4) 0–3.3x10-4 (5.7x10-5) 

Hotaco mineral 14 Yes 0–4.3x10-4 (5.6x10-5) 0–1.9x10-4 (2.1x10-5) 

Ny Hotaco mineral 

Other with water 

soluble binder 

2 

12 

Yes 

Yes 

6–13x10-5 (9.5x10-5) 

0–3.6x10-4 (5.9x10-5) 

Not detected 

0–7.0x10-5 (1.4x10-5) 

Soft mineral wool 

sealed on three sides 

13 No 0–3.4x10-4 (2.6x10-5) 0–1.0x10-4 (8.0x10-6) 

Hard mineral wool 

sealed on three sides 

9 No 0–1.3x10-4 (3.1x10-5) 0–7.0x10-5 (1.0x10-5) 

Unsealed mineral 

wool 

12 No 0–1.03x10-3 (1.8x10-4) 0–4.0x10-4 (6.7x10-5) 

Sealed mineral wool 

on all six surfaces 

9 No 0–6.1x10-4 (9.4x10-5) 0–2.4x10-4 (4.6x10-5) 

Batts on top of 

perforated panels 

No synthetic vitreous 

fiber (control group) 

11 

12 

No 

Not applicable 

0–1.0x10-4 (1.7x10-5) 

0–6.2x10-4 (6.2x10-5) 

0–6.0x10-5 (9.0x10-6) 

0–1.3x10-4 (1.8x10-5) 

a

Schneider et al. 1990 

b

Contains Danish product names 
SYNTHETIC VITREOUS FIBERS 188 

6. POTENTIAL FOR HUMAN EXPOSURE 

6.4.2 Water 

No data exist regarding the ambient levels of synthetic vitreous fibers in water. 

6.4.3 Sediment and Soil 

No data exist regarding the ambient levels of synthetic vitreous fibers in soil or sediment. 

6.4.4 Other Environmental Media 

No data exist regarding the levels of synthetic vitreous fibers in foods, plants, or animals. 

6.5 GENERAL POPULATION AND OCCUPATIONAL EXPOSURE 

The exposure of the general population (non-occupational exposure) to synthetic vitreous fibers in both 

indoor and outdoor air is low. Persons that install their own home insulation may briefly be exposed to 

higher than normal levels during the installation; however, these exposures can be significantly reduced 

with the use of protective equipment such as ventilators and gloves. Furthermore, it has been shown that 

the airborne levels of synthetic vitreous fibers attenuate rapidly following installation (Jaffrey 1990; 

Miller et al. 1995). No exposures from food, drinking water, or other environmental media are expected. 

A recent study measured the density (fibers/mm2

) of synthetic vitreous fibers on material surfaces (desks, 

floors, shelves, etc.) inside 20 buildings located in Cambridge and Boston, Massachusetts (Vallarino et al. 

2003). It was determined that nearly 60% of the samples collected had zero or one countable synthetic 

vitreous fiber when using NIOSH Method 7400 and counting rules B. Only about 4% of the samples had 

densities >1 fiber/mm2

. A second survey was undertaken that analyzed the synthetic vitreous fibers on 

the surface of objects inside 20 buildings located in 10 cities within the United States (Vallarino et al. 

2003). In this survey, counting rules A were employed, which allows fibers possessing diameters >3 μm 

to be counted. Using counting rules A, the number of samples having zero countable synthetic vitreous 

fibers decreased from about 43 to 14%. It was also shown that surfaces seldom contacted or cleaned (tops 

of bookcases or high shelves) had higher fiber loadings than surfaces that received frequent contact. 
SYNTHETIC VITREOUS FIBERS 189 

6. POTENTIAL FOR HUMAN EXPOSURE 

Although there was a large degree of variability in the fiber loadings, it is clear that only low levels of 

synthetic vitreous fibers are expected to be present on common surfaces within buildings used by the 

general population. 

The airborne levels of synthetic vitreous fibers have been shown to be higher under occupational settings 

as compared to ambient air levels, and thus, occupational exposure is far greater than the exposure for the 

general population. Esmen and Erdal (1990) concluded that occupational exposure is several orders of 

magnitude greater than environmental exposure. The Occupational Safety and Health Administration 

(OSHA) estimates that there are over 250,000 workers in the United States who are exposed to synthetic 

vitreous fibers in manufacturing and downstream use (OSHA 2002). This number is expected to increase 

as use of products containing synthetic vitreous fibers increases. 

Workers involved in the installation of fiberglass insulating material are exposed to synthetic vitreous 

fibers through both dermal and inhalation routes. Airborne fiber levels were studied by PCM during the 

installation of fibrous glass insulating materials in northern California (NIOSH 1976). The concentration 

of fibrous glass in 40 air samples obtained during the installation of this material ranged from 5.0x10-4 to 

2.41 fibers/cc (0.406 fiber/cc, arithmetic mean) with diameters in the range of 0.30–25.0 μm (6.5 μm, 

arithmetic mean). These airborne levels were 2–3 orders of magnitude greater than levels typically found 

in ambient air (Balzer 1971; NIOSH 1976; Switala et al. 1994). Differences were noted in the 

concentration of glass fibers in personal air samples when comparing the installation of batt-type material 

with blown-in insulation. The arithmetic mean concentration of total glass fibers during the installation of 

batt-type insulation was 0.13 fiber/cc and the arithmetic mean respirable glass fiber concentration was 

0.042 fiber/cc as determined by PCM (Jacob et al. 1992). The personal air concentrations were higher for 

applications involving blown-in insulation wool as compared to batt-type material. The arithmetic mean 

concentrations of total glass wool fibers were 0.68 fiber/cc (cubed blown wool) and 1.7 fibers/cc (milled 

blown wool) during the installation process. The corresponding arithmetic mean concentrations of 

respirable glass wool fibers were 0.30 fiber/cc for the milled blown wool and 0.82 fiber/cc for the cubed 

blown wool (Jacob et al. 1992). The levels of airborne respirable glass fibers were shown to decrease 

significantly after installation, with levels on the order of 1x10-4 fiber/cc 1 day after installation (Jacob et 

al. 1992). The respirable airborne concentrations of refractory ceramic fibers, rock wool, and glass wool 

fibers were measured by PCM and TEM at five construction sites using products containing these 

materials (Perrault et al. 1992). The greatest airborne levels were observed during the removal of 

refractory ceramic fiber insulating material from the inside walls of industrial furnaces, with geometric 
SYNTHETIC VITREOUS FIBERS 190 

6. POTENTIAL FOR HUMAN EXPOSURE 

mean concentrations ranging from 0.39 to 3.51 fibers/cc. The geometric mean concentration of respirable 

fibers during the installation of blown in rock wool in the attic of a residential apartment building was 

0.32 fiber/cc, while the geometric mean concentration was 0.15 fiber/cc for sprayed-on rock wool 

insulation at an industrial construction site. The lowest airborne levels were observed during the 

installation of fiberglass panels around ventilation ducts at an industrial construction site, with a 

geometric mean concentration of 0.010 fiber/cc (Perrault et al. 1992). Using TEM and PCM, the mean 

concentration of respirable airborne fibers were measured in the range of 0.080–1.76 fibers/cc during the 

installation of either glass wool or rock wool insulating material in 12 houses in England (Jaffrey 1990). 

The lowest airborne concentrations were observed during the installation of rock wool blanket material, 

and the highest level occurred during the installation of a fine glass wool blanket material, in which 

approximately 80% of the fibers had diameters <1 μm. 

In a study of four facilities producing fibrous glass insulation and one producing fibrous glass textile 

products, the range of concentrations for total respirable fibers having lengths >5 μm were reported as not 

detected to 1.97 fibers/cc, with mean levels in the range of 0.020–0.97 fiber/cc (Johnson et al. 1969). No 

data were provided regarding what percentage of total fiber counts were glass fibers as opposed to other 

fibers, and respirable fibers in this study were defined as fibers having a diameter <5 μm, rather than the 

currently accepted value of <3 μm. The airborne level of fibers in various parts of 16 manufacturing 

facilities producing glass wool, continuous glass filament, rock and slag wool, and refractory ceramic 

fibers were measured by Esmen et al. (1979a, 1979b), and the details of this study have been summarized 

in other publications (IARC 1988, 2002; WHO 1988). Table 6-2 shows the levels of total suspended 

particulate matter in various regions of these 16 plants, and Table 6-3 shows the corresponding 

concentrations of total airborne fibers measured by PCM. The greatest airborne fiber levels of were 

observed at a plant producing refractory ceramic and special purpose fibers (plant 15), where the nominal 

fiber diameter of the product ranged from 0.050 to 1.6 μm. Additional studies employing transmission 

electron microscopy to detect small diameter fibers showed airborne fiber levels as high as 6.49 fibers/cc 

for this location. More recent monitoring data on workplace airborne levels confirm that higher 

concentrations are observed under occupational settings as compared to the levels observed under nonoccupational conditions. In a study of airborne fiber levels during 11 different manufacturing operations 

involving Owens-Corning Fiberglass insulation products, the mean concentration of airborne total glass 

fibers ranged from 0.0020 to 0.14 fiber/cc and the mean concentration of respirable glass fibers ranged 

from 0.0010 to 0.071 fiber/cc as determined by PCM (Jacob et al. 1993). The airborne fiber levels were 
SYNTHETIC VITREOUS FIBERS 191 

6. POTENTIAL FOR HUMAN EXPOSURE 

Table 6-2. Concentrations (mg/m3) of Total Suspended Airborne Particulate 

Matter in 16 Facilities in the United Statesa
 

Quality Shipping Overall 

Forming Production Manufacturing Maintenance control mean mean 

Plant mean (SD) mean (SD) mean (SD) mean (SD) mean (SD) (SD) (SD) 

1 0.47 (0.47) 1.04 (1.34) 0.96 (0.96) 0.71 (0.45) 0.21 (0.12) 0.39 (0.09) 0.89 (1.12) 

2 1.65 (1.17) 2.53 (2.30) 2.28 (1.51) 2.05 (1.32) 1.53 (0.63) 1.34 (0.58) 1.94 (1.68) 

3 No data 0.51 (0.30) No data 0.83 (0.61) No data 0.70 (0.42) 0.65 (0.46) 

4 1.22 (0.51) 0.77 (0.49) 1.23 (0.95) 2.08 (4.40) 0.52 (0.14) 1.32 (0.96) 1.24 (2.26) 

5 0.76 (0.25) 0.67 (1.52) 0.29 (0.95) 0.55 (0.32) 0.09 (No 0.62 (0.33) 0.60 (1.04) 

data) 

6 1.30 (0.71) 1.77 (2.23) 0.51 (0.39) 2.00 (2.50) 0.49 (0.82) 0.45 (0.19) 1.17 (1.72) 

7 2.18 (1.62) 2.05 (0.31) 4.31 (4.03) 6.72 (7.84) No data 1.77 (1.02) 4.00 (4.27) 

8 No data 8.48 (9.02) 1.17 (0.55) 4.64 (8.28) No data 0.84 (0.67) 4.73 (8.69) 

9 1.18 (0.48) 1.90 (1.52) 1.14 (0.53) 1.33 (0.57) No data 1.08 (0.46) 1.33 (1.02) 

10 2.45 (0.93) 0.75 (0.47) 0.73 (0.33) 1.25 (1.07) 0.32 (0.09) 0.69 (0.15) 1.07 (0.91) 

11 2.18 (1.64) 1.08 (1.82) 0.87 (0.46) 1.26 (0.49) 1.25 (No 1.04 (0.41) 1.37 (1.09) 

data) 

12 0.34 (0.35) 0.20 (0.30) 0.28 (0.26) 0.53 (0.26) 0.53 (0.66) 0.88 (0.08) 0.21 (0.16) 

13 4.10 (No 1.34 (0.46) 1.19 (1.08) 1.80 (1.69) No data 1.31 (0.59) 1.40 (1.08) 

data) 

14 3.00 (1.37) 0.85 (0.59) 1.06 (0.47) 1.57 (1.41) No data 0.91 (0.72) 1.42(1.21) 

15 0.30 (0.21) 0.61 (0.51) 1.08 (0.80) 1.09 (0.75) 1.66 (0.73) 0.54 (0.18) 0.75 (0.67) 

16 0.77 (0.46) 0.82 (0.69) 0.86 (0.52) 1.79 (1.50) 0.44 (No 0.76 (0.53) 1.07 (1.02) 

data) 

a

Esmen et al. 1979b; measurements obtained with phase contrast microscopy 

SD = standard deviation 
SYNTHETIC VITREOUS FIBERS 192 

6. POTENTIAL FOR HUMAN EXPOSURE 

Table 6-3. Concentrations (fiber(s)/cc) of Total Airborne Fibers in 16 Facilities in 

the United Statesa 

Forming Production Manufactur- Mainten- Quality Shipping Overall 

ND area mean area mean ing area ance area control area area mean mean 

Plant μm (SD) (SD) mean (SD) mean (SD) mean (SD) (SD) (SD) 

1 1–12 0.002 0.38 (0.32) 0.03 (0.02) 0.02 (0.02) 0.07 (0.10) 0.01 (0.001) 0.01 

(0.001) (0.25) 

2 6 0.07 (0.03) 0.17 (0.14) 0.12 (0.11) 0.08 (0.05) 0.19 (0.16) 0.07 (0.06) 0.11 

(0.12) 

3 3–6 No data 0.02 (0.02) No data 0.07 (0.18) No data 0.005 (0.01) 0.04 

(0.1) 

4 1–6 0.01 (0.004) 0.07 (0.12) 0.04 (0.05) 0.03 (0.02) 0.01 (0.01) 0.02 (0.01) 0.04 

(0.08) 

5 8 0.02 (0.01) 0.03 (0.02) 0.03 (0.02) 0.02 (0.01) 0.03 (No 0.03 (0.01) 0.02 

data) (0.02) 

6 5–15 0.05 (0.10) 0.01 (0.01) 0.008 (0.01) 0.01 (0.03) 0.01 (0.02) 0.005 0.01 

(0.004) (0.03) 

7 5 0.15 (0.03) 0.24 (0.12) 0.43 (0.32) 0.44 (0.37) No data 0.15 (0.17) 0.34 

(0.35) 

8 7–10 No data 0.03 (0.02) 0.04 (0.03) 0.01 (0.01) No data 0.01 (0.01) 0.02 

(0.02) 

9 7–10 0.02 (0.02) 0.01 (0.01) 0.02 (0.07) 0.01 (0.006) No data 0.004 0.02 

(0.002) (0.01) 

10 6–16 0.001 0.003 0.004 0.002 0.003 0.002 0.002 

(0.001) (0.004) (0.004) (0.003) (0.003) (0.002) (0.003) 

11 7 0.09 (0.11) 0.05 (0.03) 0.04 (0.03) 0.04 (0.04) 0.08 (0.08) 0.03 (0.02) 0.05 

(0.05) 

12 6–115 0.01 (0.01) 0.020 0.01 (0.004) 0.01 (0.02) 0.01 (0.003) 0.007 0.01 

(0.030) (0.005) (0.02) 

13 7 0.58 (No 0.08 (0.06) 0.11 (0.17) 0.09 (0.08) No data 0.03 (0.02) 0.10 

data) (0.10) 

14 6–13 0.01 (0.01) 0.04 (0.09) 0.05 (0.05) 0.05 (0.13) No data 0.03 (0.03) 0.04 

(0.03) 

15 0.05– 0.19 (0.22) 0.92 (1.02) 1.56 (3.79) 0.11 (0.10) 0.89 (0.33) 0.10 (0.09) 0.78 

1.6 (2.1) 

16 6–10 0.02 (0.01) 0.02 (0.02) 0.05 (0.03) 0.07 (0.23) 0.04 (No 0.02 (0.01) 0.04 

data) (0.12) 

a

Esmen et al. 1979b 

ND = nominal diameter; SD = standard deviation 
 

SYNTHETIC VITREOUS FIBERS 193 

6. POTENTIAL FOR HUMAN EXPOSURE 

also studied during the removal of pipe installation and ceiling boards. For these removal processes, the 

mean airborne concentration of total glass fibers was 0.10 fiber/cc and the mean airborne concentration of 

respirable glass fibers was 0.042 fiber/cc (Jacob et al. 1993). While these levels are greater than levels 

found in ambient air, they are far lower than a 1992 proposed OSHA exposure limit of 1 fiber/cc per 

8-hour time-weighted-average (TWA) (OSHA 2002). 

The North American Insulation Manufacturers Association (NAIMA) has recently developed a Health 

and Safety Partnership (HSPP) with the participation and oversight of OSHA (Marchant et al. 2002; 

Maxim et al. 2003a). As part of this program, a database that estimates the level of potential exposure to 

respirable fibers from fiber glass, rock wool, and slag wool was developed. Textile glass fibers were not 

included in the program because they are generally considered non-respirable due to their relatively large 

nominal diameters. The database contains current information regarding time-weighted average exposure 

levels, which are categorized by product type and specific work function. Information from this database 

regarding exposure by industrial sector is provided in Table 6-4. Additional exposure data categorized by 

product description and job description are presented in Tables 6-5 and 6-6, respectively. Maxim et al. 

(2003a) estimated the probable cumulative lifetime exposure (fiber-month/cc) to persons that install 

fiberglass or rock/slag wool insulation materials in residential, commercial and industrial buildings. This 

analysis concluded that due to smaller exposure times, both do it yourself and professional insulation 

installers had much lower lifetime exposures than workers employed in the manufacturing of fiberglass, 

rock/slag wool products (Maxim et al. 2003a). The authors noted that recent epidemiological studies 

have concluded that there is no significant increase in respiratory system cancer among the manufacturing 

cohorts, and therefore, there is even less risk for installers (Maxim et al. 2003a). 

The concentration of respirable (defined in this study as having diameters ≤3 μm) refractory ceramic 

fibers in personal air samples in seven manufacturing plants located in France, the United Kingdom, and 

Germany ranged from about 0.2 to 1.0 fiber/cc as determined by PCM (Trethowan et al. 1995). The 

levels of respirable airborne refractory ceramic fibers were studied by PCM at five manufacturing plants 

located in the United States over a 6-year period to assess differences in exposure levels during different 

work shifts in the plants (Hall et al. 1997). The geometric mean TWA exposure for all shifts at these five 

plants ranged from 0.080 to 0.35 fiber/cc, and little differences were observed in the level of exposure and 

which shift the measurements were obtained. Based on a 2-year survey of occupational exposure to 

refractory ceramic fibers in the United Kingdom, some typical exposure levels categorized by process 
SYNTHETIC VITREOUS FIBERS 194 

6. POTENTIAL FOR HUMAN EXPOSURE 

Table 6-4. Exposures to Synthetic Vitreous Fibers Categorized by
 

Industrial Sectora
 

Industrial sector Samples Mean (f/cc) Standard deviation Median Range 

Glass wool manufacturing 1,648 0.23 0.53 0.03 0.01–4.63 

Glass wool fabrication 475 0.28 0.49 0.10 0.01–3.80 

Glass wool installation 344 0.38 0.73 0.16 0.01–7.49 

Glass wool retrofit/removal 6 0.26 0.26 0.21 0.03–0.74 

All glass wool 2,473 0.26 0.55 0.05 0.01–7.49 

Mineral wool manufacturing 429 0.20 0.19 0.15 0.01–1.41 

Mineral wool installation 74 0.15 0.17 0.09 0.02–0.82 

Mineral wool retrofit/removal 2 0.10 0.01 0.10 0.10–0.11 

All mineral wool 505 0.19 0.19 0.14 0.01–1.41 

a

Marchant et al. 2002. Exposures are presented as 8-hour time-weighted average (TWA) exposures. 
 

 

 

 

SYNTHETIC VITREOUS FIBERS 195 

6. POTENTIAL FOR HUMAN EXPOSURE 

Table 6-5. Exposures to Synthetic Vitreous Fibers Categorized by Product Typea 

Product type Samples Mean (f/cc) SDb (f/cc) Median (f/cc) Range (f/cc) 

Glass Wool Manufacturing 

Air handling products 12 0.03 0.03 0.02 0.01–0.13 

Aircraft insulation 67 0.19 0.36 0.06 0.01–2.29 

Appliance insulation 28 0.12 0.29 0.03 0.01–1.30 

Automotive insulation 102 0.02 0.03 0.01 0.01–0.18 

Separator and filtration media 376 0.80 0.84 0.51 0.01–4.63 

Blowing wool with binder 71 0.04 0.03 0.03 0.01–0.02 

Blowing wool without binder 53 0.11 0.12 0.08 0.01–0.49 

High-density board 14 0.02 0.02 0.01 0.01–0.09 

Pipe insulation 114 0.05 0.10 0.02 0.01–0.70 

Batts and blankets 472 0.05 0.09 0.02 0.01–0.97 

Otherc 339 0.07 0.18 0.02 0.01–2.30 

Glass Wool Installation 

Air handling products 11 0.28 0.34 0.23 0.02–1.23 

Appliance insulation 31 0.08 0.16 0.02 0.01–0.06 

Automotive insulation 17 0.02 0.02 0.01 0.01–0.05 

Blowing wool with binder 19 0.30 0.30 0.24 0.04–1.13 

Blowing wool without binder 133 0.79 1.02 0.50 0.01–7.49 

Cavity loose fill insulation 12 0.15 0.12 0.11 0.04–0.47 

Pipe insulation 28 0.05 0.05 0.03 0.01–0.19 

Batts and blankets 62 0.17 0.10 0.16 0.01–0.46 

Otherd 25 0.05 0.04 0.02 0.01–0.16 

Glass Wool Fabrication 

Acoustical panels 11 0.07 0.07 0.03 0.01–0.23 

Air handling products 66 0.05 0.05 0.03 0.01–0.22 

Appliance insulation 37 0.14 0.15 0.10 0.01–0.65 

Automotive insulation 19 0.05 0.04 0.03 0.01–0.10 

Battery separator media 122 0.55 0.77 0.20 0.01–3.80 

Air and water filters 146 0.32 0.41 0.15 0.01–1.90 

Othere 74 0.10 0.10 0.09 0.01–0.64 

Mineral Wool Manufacturing 

Ceiling panel/tile 412 0.20 0.19 0.15 0.01–1.41 

Otherf 17 0.06 0.04 0.05 0.01–0.15 
 

SYNTHETIC VITREOUS FIBERS 196 

6. POTENTIAL FOR HUMAN EXPOSURE 

Table 6-5. Exposures to Synthetic Vitreous Fibers Categorized by Product Typea 

Product type Samples Mean (f/cc) SDb (f/cc) Median (f/cc) Range (f/cc) 

Mineral Wool Installation 

Ceiling panel/tile 33 0.23 0.21 0.17 0.02–0.82 

Spray–on fireproofing 15 0.08 0.10 0.05 0.02–0.42 

Insulation batts/blankets 12 0.09 0.04 0.08 0.04–0.16 

Otherf

 14 0.11 0.11 0.06 0.02–0.40 

a

Marchant et al. 2002. Exposures are presented as 8-hour time-weighted average (TWA) exposures. b

Standard deviation 

c

Includes acoustical panels and nonspecified products 

d

Includes flex duct and nonspecified products 

e

Includes aircraft and pipe insulation; batts, blankets with binder, and nonspecified products 

f

Includes air handling board, appliance insulation, blowing wool with binder, cavity loose fill insulation, pipe insulation, 

safing blanket, and board 
SYNTHETIC VITREOUS FIBERS 197 

6. POTENTIAL FOR HUMAN EXPOSURE 

Table 6-6. Exposures to Synthetic Vitreous Fibers Categorized by Job Typea 

Job description Samples Mean (f/cc) SDb (f/cc) Median (f/cc) Range (f/cc) 

Glass Wool Manufacturing 

Scrap baler/compactor 29 0.05 0.05 0.04 0.01–0.25 

Batch/binder mixer 40 0.18 0.33 0.04 0.01–1.30 

Cutting/hot press mold 109 0.04 0.12 0.01 0.01–0.88 

Forming 289 0.11 0.23 0.02 0.01–2.30 

General laborer/maintenance 62 0.11 0.33 0.02 0.01–2.29 

Packaging 890 0.34 0.67 0.04 0.01–4.63 

Quality control/research 75 0.18 0.23 0.09 0.01–1.20 

Sewing/laminating/assembly 91 0.08 0.11 0.03 0.01–0.62 

Shipping/receiving 53 0.01 0.01 0.01 0.01–0.06 

Otherc 10 0.11 0.20 0.05 0.01–0.66 

Glass Wool Installation 

Assembly 34 0.04 0.06 0.02 0.01–0.35 

Feeder 63 0.36 0.37 0.20 0.01–2.18 

Installer 232 0.45 0.85 0.18 0.01–7.49 

Otherd 9 0.16 0.14 0.07 0.03–0.37 

Mineral Wool Manufacturing 

Supervisory 17 0.13 0.11 0.10 0.01–0.40 

Forming 162 0.24 0.22 0.18 0.01–1.41 

Maintenance 79 0.18 0.16 0.14 0.01–0.79 

Packaging 62 0.25 0.20 0.23 0.01–1.00 

Quality control 20 0.21 0.21 0.16 0.01–0.80 

Shipping/receiving 55 0.14 0.14 0.08 0.01–0.57 

Othere 34 0.09 0.10 0.05 0.01–0.42 

Mineral Wool Installation 

Installers 65 0.16 0.17 0.10 0.02–0.82 

Othere

 9 0.09 0.12 0.05 0.02–0.40 

a

Marchant et al. 2002. Exposures are presented as 8-hour time-weighted average (TWA) exposures. b

Standard deviation 

c

Includes administration and blowing wool chopper operator and nodulator.

d

Includes cutting/sawing and maintenance. 

e

Includes assembly, cutting/sawing, vehicle driver production, warehousing, feeder, and general laborer.
 
 

 

SYNTHETIC VITREOUS FIBERS 198 

6. POTENTIAL FOR HUMAN EXPOSURE 

description or job type were compiled (Friar and Phillips 1989). The results of this survey are 

summarized in Table 6-7 While high levels of exposure were estimated for certain job descriptions, it 

was noted that over 60% of the exposure levels fall within the 0–0.5 fiber/cc range (Friar and Phillips 

1989). 

The results of a comprehensive 54-month workplace monitoring study for exposure to refractory ceramic 

fibers in the United States have been published (Mast et al. 2000; Maxim et al. 1994). Although large 

differences were noted in the TWA exposures to workers performing various job functions, it was 

reported that of the nearly 3,000 samples obtained at facilities that process or use refractory ceramic 

fibers, 77% of the TWA measurements were below the industry recommended exposure guideline of 

0.5 fiber/cc (Mast et al. 2000). It was also reported that approximately 84% of the samples obtained at 

refractory ceramic fiber producing facilities were below the recommended exposure guideline. Workers 

involved in the removal and installation of insulation from furnaces, as well as the finishing (use of drill 

presses, sanding, and sawing) of refractory ceramic fibers had the highest TWA exposures, while workers 

involved in mixing/forming, fiber manufacturing, product assembly, and auxiliary job categories had the 

lowest TWA. The TWA exposures ranged from about 0.2 fiber/cc for auxiliary and assembly workers to 

about 1.2 fibers/cc for workers involved in the removal of refractory ceramic fiber containing insulating 

material (Maxim et al. 1994). A significant decrease in the TWA exposure to workers over the period of 

1990–1998 was observed as engineering controls and respirator use has improved (Mast et al. 2000). 

Exposure to refractory ceramic fibers may pose an additional health hazard for workers involved in the 

removal of ceramic fiber insulation from high temperature industrial furnaces, since refractory ceramic 

fibers may be partially converted to quartz, cristobalite, and tridymite at elevated temperatures (Maxim et 

al. 1999). Tests performed on three refractory ceramic fiber containing insulation blankets showed that 

between 3 and 21% of the bulk fibers had been converted to cristobalite at temperatures in the range of 

500–2,550 °F, with the majority of devitrification occurring on the surface layers of the hot face (Gantner 

1986). The percentage of cristobalite in corresponding air samples ranged from 4.0 to 14.7% (Gantner 

1986). No quartz or tridymite was detected. An analysis of the monitoring data led to the conclusion that 

personal exposure to cristobalite while removing insulation from the furnaces reached or exceeded the 

threshold limit value of 0.05 mg/m3

 in about 75% of the samples (Gantner 1986). The phase changes and 

devitrification process of refractory ceramic fibers that occur as a function of temperature have been 

discussed elsewhere (Brown et al. 1992). A study was conducted to determine the level of exposure to 
SYNTHETIC VITREOUS FIBERS 199 

6. POTENTIAL FOR HUMAN EXPOSURE 

Table 6-7. Typical Exposures in the Manufacture and Use of 

Refractory Ceramic Fibersa
 

Process description or job Exposure level (fiber(s)/cc) 

Manufacture 

Needle operator 0.5 

Baling raw fiber 0.4 

Fiber chopping 0.8 

Product reeling 0.8 

Bagging/chopping raw fiber 1.2 

Mixing during product formation 0.4 

Packing products 0.02 

Use 

Wrapping refractory ceramic fiber blanket around pipe weld 0.8 

Stripping and relining furnace panel 1.2 

Kiln building 1.75 

Handling blanket refractory ceramic fiber 1.0 

Machining and ventilation control of refractory ceramic fiber fireboard 0.6 

Insulation work using blanket 1.0 

Handling operations; manual handling, but with little cutting or machining 0.1 

a

Friar and Phillips 1989 
SYNTHETIC VITREOUS FIBERS 200 

6. POTENTIAL FOR HUMAN EXPOSURE 

refractory ceramic fibers during the installation and removal of insulation in 13 furnaces situated in 

6 refineries and 2 chemical plants located in the United States (Cheng et al. 1992). The majority of 

exposures to refractory ceramic fibers were found to be low, with 8-hour TWA exposure levels of 

≤0.2 fiber/cc for most of the tasks involved. However, airborne levels as high as 17 fibers/cc were 

observed when removing refractory ceramic fiber containing blankets inside of furnaces or when welders 

cut through crude oil furnace tubes when cutting away damaged metal parts while repairing a furnace 

(Cheng et al. 1992). Furthermore, the study found that workers who replaced worn out refractory ceramic 

fiber modules from the furnaces had exposure to cristobalite in dust samples ranging from 0.03 to 

0.2 mg/m3

, with a geometric mean of 0.06 mg/m3, which is above the OSHA established permissible 

exposure limit (PEL) of 0.05 mg/m3

 (Cheng et al. 1992). A more recent study conducted from 1993 to 

1998 found that respirable quartz was detectable in only 14 of the 158 samples taken during the removal 

of insulation from industrial furnaces, respirable cristobalite was only detectable in 3 samples, and 

respirable tridymite was only detected in 1 sample (Maxim et al. 1999). However, the short sampling 

time of many of these collections led to relatively poor limits of detection due to the low volume of air 

collected during the analysis, and longer sampling times would likely indicate a higher percentage of 

detectable crystalline silica exposure. 

6.6 EXPOSURES OF CHILDREN 

This section focuses on exposures from conception to maturity at 18 years in humans. Differences from 

adults in susceptibility to hazardous substances are discussed in Section 3.7 Children’s Susceptibility. 

Children are not small adults. A child’s exposure may differ from an adult’s exposure in many ways. 

Children drink more fluids, eat more food, breathe more air per kilogram of body weight, and have a 

larger skin surface in proportion to their body volume. A child’s diet often differs from that of adults. 

The developing human’s source of nutrition changes with age: from placental nourishment to breast milk 

or formula to the diet of older children who eat more of certain types of foods than adults. A child’s 

behavior and lifestyle also influence exposure. Children crawl on the floor, put things in their mouths, 

sometimes eat inappropriate things (such as dirt or paint chips), and spend more time outdoors. Children 

also are closer to the ground, and they do not use the judgment of adults to avoid hazards (NRC 1993). 

Children may be exposed to low levels of synthetic vitreous fibers in the same ways that adults are 

exposed outside the workplace. This exposure primarily occurs from inhaling low levels of synthetic 
 

 

SYNTHETIC VITREOUS FIBERS 201 

6. POTENTIAL FOR HUMAN EXPOSURE 

vitreous fibers from ambient and household air, or air from schools and other public buildings. 

Differences in breathing patterns, airflow velocity, and airway geometry between adults and children can 

result in age-related differences in deposition of inhaled particles in the respiratory tract (Phalen et al. 

1985). Deposition of particles in various regions of the respiratory tract in children may be higher or 

lower than in adults depending on particle size, but for particles with diameters <1 μm, fractional 

deposition in the alveolar, tracheobronchial, and nasopharyngeal regions in 2-year-old children has been 

estimated to be about 1.5 times higher than in adults (Xu and Yu 1986). A study conducted by Schneider 

et al. (1996) attempted to evaluate the personal exposure of individuals residing in different parts of 

Europe to organic and inorganic fibers. It was determined that out of the four groups studied (suburban 

school children, rural retired persons, office workers, and taxi drivers), schoolchildren had the greatest 

exposure to total fiber counts. The mean concentration of total respirable fibers in the personal air 

samples of schoolchildren was 0.02 fiber/cc (Schneider et al. 1996). However, it was shown that the 

majority of respirable fibers were organic fibers and inorganic fibers other than synthetic vitreous fibers 

(particularly gypsum), and the level of exposure to fibers consistent with synthetic vitreous fibers was 

very low. 

The airborne fiber concentration in kindergartens in Denmark was studied to determine if there was a 

correlation between respiratory problems and fiber concentrations in the schools (Rindel et al. 1987; 

Schneider 1986). The mean concentrations of respirable fibers in schools with ceiling boards containing 

synthetic vitreous fibers with water-soluble binders and resin binders were 1.1x10-4 and 9.7x10-5 fiber/cc, 

respectively. The mean concentration in kindergartens using ceiling boards that did not contain synthetic 

vitreous fibers was 4.1x10-5 fiber/cc. It was concluded that no correlation existed between respiratory 

symptoms or disease and synthetic vitreous fibers exposure (Rindel et al. 1987; Schneider 1986). 

Since children tend to play on carpets and floors, they may also be exposed to synthetic vitreous fibers 

that have been deposited on theses surfaces, but the levels are expected to be very low (Schneider et al. 

1990). 

6.7 POPULATIONS WITH POTENTIALLY HIGH EXPOSURES 

The people most likely to have high exposure to synthetic vitreous fibers are workers who come into 

contact with products containing these fibers while on the job. This includes people involved in the 

manufacture of synthetic vitreous fiber-containing products, and also people who install, service, remove, 
 

 

SYNTHETIC VITREOUS FIBERS 202 

6. POTENTIAL FOR HUMAN EXPOSURE 

or use these products. Workers engaged in the demolition of buildings with synthetic vitreous fibercontaining materials are also potentially exposed. Workers involved in the installation or servicing of 

furnaces that contain refractory ceramic fiber insulation may also be exposed to quartz, cristobalite, and 

tridymite. Workers may also carry home deposited synthetic vitreous fibers from their clothing or in their 

hair, resulting in exposure of family members; however, this is not likely to be of concern at the present. 

Lung tissue samples were obtained from the autopsies of 145 former employees of 17 synthetic vitreous 

fiber plants located in the United States (McDonald et al. 1990). Levels of total fibers were 

approximately 60% greater in workers than in people who were not occupationally exposed, but the 

majority of detectable fibers were not synthetic vitreous fibers. While certain fibers were classified as 

synthetic vitreous fibers, no further identification as to exact type of synthetic vitreous fibers was 

possible. Furthermore, only four individuals that were occupationally exposed had synthetic vitreous 

fibers lung concentrations >0.2 fiber/μg lung tissue (one worker had a concentration of 1 fiber/μg), the 

rest had concentrations below 0.2 fiber/μg (McDonald et al. 1990). The geometric mean fiber length, 

fiber diameter, and aspect ratio were 7.5 μm, 1.0 μm, and 8.0, respectively, for those occupationally 

exposed, while the values for the referents were 6.6 μm, 1.2 μm, and 6.1, respectively. Autopsy reports 

indicated that synthetic vitreous fibers were not detected in the lung tissue of one female and eight male 

subjects who were employed in glass wool production plants for at least 1 year between 1946 and 1978 

(Gibbs et al. 1996). These findings suggest that glass wool and other types of synthetic vitreous fibers do 

not have a prolonged durability in human lung tissue. 

Although data are scarce, current monitoring data do not support the assumption that persons residing 

near plants where synthetic vitreous fibers are produced will be exposed to higher levels of these fibers in 

the ambient air than persons who reside distal from such plants (Switala et al. 1994). It is noted that in 

1990, the EPA intended to regulate all synthetic vitreous fibers under the Clean Air Act, but instead chose 

to list only those mineral fibers having an average diameter less than 1 μm, following an industry-funded 

study, which showed that emissions of such fibers from synthetic vitreous fiber producing facilities were 

insignificant (EPA 1992). 

6.8 ADEQUACY OF THE DATABASE 

Section 104(i)(5) of CERCLA, as amended, directs the Administrator of ATSDR (in consultation with the 

Administrator of EPA and agencies and programs of the Public Health Service) to assess whether 
 

 

 

SYNTHETIC VITREOUS FIBERS 203 

6. POTENTIAL FOR HUMAN EXPOSURE 

adequate information on the health effects of synthetic vitreous fibers is available. Where adequate 

information is not available, ATSDR, in conjunction with NTP, is required to assure the initiation of a 

program of research designed to determine the health effects (and techniques for developing methods to 

determine such health effects) of synthetic vitreous fibers. 

The following categories of possible data needs have been identified by a joint team of scientists from 

ATSDR, NTP, and EPA. They are defined as substance-specific informational needs that if met would 

reduce the uncertainties of human health assessment. This definition should not be interpreted to mean 

that all data needs discussed in this section must be filled. In the future, the identified data needs will be 

evaluated and prioritized, and a substance-specific research agenda will be proposed. 

6.8.1 Identification of Data Needs 

Physical and Chemical Properties. The physical and chemical properties of synthetic vitreous 

fibers are generally well characterized (see Chapter 4), and there does not appear to be a need for further 

research in this area. However, continuing characterization of new fibers, particularly the physical 

dimensions of the fibers and products, will be necessary as they are produced. 

Production, Import/Export, Use, Release, and Disposal. Data regarding the import and export 

volumes of glass fibers, refractory ceramic goods, and mineral wool exist (USDOC 2002). Although 

some production volume data are available for synthetic vitreous fibers (GMIC 2002; Mast et al. 2000), 

more recent data would be useful. There is also a data need to have an estimate of the annual amount of 

synthetic vitreous fiber containing material that is either disposed of at landfills or incinerated at 

hazardous waste incinerators. Synthetic vitreous fibers are primarily used for insulation purposes and 

reinforcing other materials (IARC 1988, 2002; WHO 1988). 

According to the Emergency Planning and Community Right-to-Know Act of 1986, 42 U.S.C. 

Section 11023, industries are required to submit substance release and offsite transfer information to the 

EPA. TRI, which contains this information for 2001, became available in 2003. This database is updated 

yearly and provides a list of industrial facilities producing, processing, and using friable asbestos and their 

emissions. 
 

SYNTHETIC VITREOUS FIBERS 204 

6. POTENTIAL FOR HUMAN EXPOSURE 

Environmental Fate. Synthetic vitreous fibers are fundamentally inert and are not considered to 

undergo transport or degradative processes in the environment analogous to organic pollutants (WHO 

1988). Additional studies on the behavior of fibers in water (processes such as change in metal ion and 

hydroxyl ion composition, adsorption to organic materials, flocculation and precipitation, etc.) would be 

helpful in evaluating water-based transport of fibers, as well as in improving methods for removal of 

fibers from water. Transport of fibers in air is governed by processes and forces that apply to all 

particulate matter, and these processes are reasonably well understood (WHO 1988). 

Bioavailability from Environmental Media. Synthetic vitreous fibers are generally insoluble and 

are not absorbed following dermal exposure. Most exposures occur to fibers in air, so the effect of 

matrices such as soil or food is largely unknown. It is possible that adsorption of fibers onto other dust 

particles could influence the location of deposition in the lung, and might even influence the cellular 

response to the fibers. Research to determine if this occurs and whether this is biologically significant 

would be helpful. 

Food Chain Bioaccumulation. No data were located on synthetic vitreous fiber levels in the tissues 

of edible organisms. However, it is not expected that either aquatic or terrestrial organisms will 

accumulate a significant number of fibers in their flesh. Consequently, food chain bioaccumulation or 

biomagnification does not appear to be of concern. No data needs have been identified at this time. 

Exposure Levels in Environmental Media. Data exist regarding the levels of synthetic vitreous 

fibers in ambient air (Balzer et al. 1971; NIOSH 1976; Switala et al. 1994) and indoor air (Gantner 1986; 

Jacob et al. 1992, 1993; Schneider et al. 1990; Trethowan et al. 1995). Generally, these levels are very 

low, with the exception of indoor air concentrations when insulating material is being installed (Jacob et 

al. 1993). No data exist regarding the levels of synthetic vitreous fibers in other environmental media 

such as water or soil. It would be useful to have airborne measurements of synthetic vitreous fibers near 

municipal landfills where construction material containing synthetic vitreous fibers are often discarded. 

Airborne levels in the vicinity of waste incinerators where synthetic vitreous fiber containing material 

may be burned would also be useful. 

Exposure Levels in Humans. The general population is exposed to low levels of synthetic vitreous 

fibers from ambient and indoor air (Balzer et al. 1971; Gantner 1986; Jacob et al. 1992, 1993; NIOSH 

1976; Switala et al. 1994). Occupational exposure is several orders of magnitude greater than exposure to 
 

SYNTHETIC VITREOUS FIBERS 205 

6. POTENTIAL FOR HUMAN EXPOSURE 

the general population (Esmen and Erdal 1990). There are few data regarding the levels of synthetic 

vitreous fibers in human tissue due to the difficulty in analyzing for these substances (Dumortier et al. 

2001; McDonald et al. 1990; Roggli 1989; Schneider and Stockholm 1981). Body burden data, 

particularly for workers frequently exposed to synthetic vitreous fibers occupationally, would be useful to 

better evaluate human exposure. 

Exposures of Children. No data exist regarding the levels of synthetic vitreous fibers in children. It 

was shown that exposure of children residing in Europe to synthetic vitreous fibers is significantly lower 

than exposure to organic and other inorganic fibers (Schneider et al. 1996). Other studies have indicated 

that there is no correlation between respiratory problems in children and synthetic vitreous fibers 

concentrations in schools (Rindel et al. 1987; Schneider 1986). Children may be exposed to these 

substances in the same ways that adults are exposed outside the workplace, from synthetic vitreous fibers 

in the air. Just as children are exposed to synthetic vitreous fibers in the same way as non-occupationally 

exposed adults, there are no childhood-specific means to decrease exposure. Because childhood exposure 

to synthetic vitreous fibers is considered low and it is difficult to analyze for synthetic vitreous fibers in 

humans, there is no data need to conduct body burden studies at this time. 

Child health data needs relating to susceptibility are discussed in Section 3.12.2 Identification of Data 

Needs: Children’s Susceptibility. 

Exposure Registries. No exposure registries for synthetic vitreous fibers were located. These 

substances are not currently one of the compounds for which a subregistry has been established in the 

National Exposure Registry. These substances will be considered in the future when chemical selection is 

made for subregistries to be established. The information that is amassed in the National Exposure 

Registry facilitates the epidemiological research needed to assess adverse health outcomes that may be 

related to exposure to synthetic vitreous fibers. 

6.8.2 Ongoing Studies 

The Federal Research in Progress (FEDRIP 2002) database provides additional information obtainable 

from a few ongoing studies that may fill in some of the data needs identified in Section 6.8.1. 
SYNTHETIC VITREOUS FIBERS 206 

6. POTENTIAL FOR HUMAN EXPOSURE 

A light-scattering-based optical sensor is being developed for the online analysis of fiber diameters during 

the manufacturing and production process of fiberglass, by Mission Research Corporation, Santa Barbara, 

California. Such a sensor will allow for the rapid measurement of fiber diameters and allow for improved 

production efficiency and control (FEDRIP 2002). The Vortec Corporation (J.G. Hnat, principal 

investigator) is developing an advanced coal-fired incinerator/glass melter as a means of eliminating the 

solid/hazardous waste disposal problems associated with the production of insulation products and 

enabling glass manufacturers to use an abundant and inexpensive fuel. 
 

SYNTHETIC VITREOUS FIBERS 207 

7. ANALYTICAL METHODS 

The purpose of this chapter is to describe the analytical methods that are available for detecting, 

measuring, and/or monitoring synthetic vitreous fibers, its metabolites, and other biomarkers of exposure 

and effect to synthetic vitreous fibers. The intent is not to provide an exhaustive list of analytical 

methods. Rather, the intention is to identify well-established methods that are used as the standard 

methods of analysis. Many of the analytical methods used for environmental samples are the methods 

approved by federal agencies and organizations such as EPA and the National Institute for Occupational 

Safety and Health (NIOSH). Other methods presented in this chapter are those that are approved by 

groups such as the Association of Official Analytical Chemists (AOAC) and the American Public Health 

Association (APHA). Additionally, analytical methods are included that modify previously used methods 

to obtain lower detection limits and/or to improve accuracy and precision. 

As discussed in Chapter 4, synthetic vitreous fibers are not a single chemical entity, but rather a group of 

amorphous polysilicates. Because the toxicity of fibrous particles appears to be related primarily to fiber 

size and chemical durability, modern analytical methods focus on providing information on these 

parameters, as well as on total number of fibers. At present, the number and size distribution of fibers in 

a sample can only be determined by direct microscopic examination. This may be performed using either 

light or electron microscopy, as discussed below. A complicating factor in the analysis of synthetic 

vitreous fibers is distinguishing small fibrous particles from asbestos or other inorganic fibers, and 

identifying and quantifying the various forms of synthetic vitreous fibers. NIOSH methods for 

determining fiber concentrations are geared to counting fibers of certain dimensions utilizing detailed 

rules as to how to count different objects (e.g., objects with split ends or attached particles) (NIOSH 

1994a). 

Light Microscopic Methods. Phase contrast microscopy (PCM) is most frequently employed to measure 

the levels of synthetic vitreous fibers. Currently, the standard method for the determination of airborne 

fibrous particles in the workplace is NIOSH Method 7400, Asbestos and Other Fibers by Phase Contrast 

Microscopy (NIOSH 1994a). In NIOSH Method 7400, samples are collected on 25 mm cellulose ester 

filters (cassette-equipped with a 50 mm electrically-conductive cowl). The filter is treated to make it 

transparent and then is analyzed by microscopy at 400–450x magnification, with phase-contrast 

illumination, using a Walton-Beckett graticule. Different counting rules may be employed when 

analyzing for synthetic vitreous fibers as compared to asbestos (termed counting rules A and B, 
 

 

SYNTHETIC VITREOUS FIBERS 208 

7. ANALYTICAL METHODS 

respectively), and these different counting rules often make comparing data from various studies difficult. 

The details of these counting rules are available in the NIOSH Manual of Analytical Methods (1994). 

Briefly, when using counting rules B, only fibers <3 μm in diameter and >5 μm in length with aspect 

ratios of ≥5:1 are counted. The rules further specify the counting of fiber ends only, with sufficient fields 

to yield at least 200 fiber ends. The counting of fibers in a minimum of 20 fields is also required for 

statistical validity. When using counting rules A, fibers with diameters >3 μm may be counted as well as 

fibers possessing an aspect ratio of ≥3:1. A recent study has concluded that using the A counting rules 

generally gives higher fiber counts than the B counting rules when analyzing the same samples (Breysse 

et al. 1999). Another recent study recommends using counting rules A in order to decrease the number of 

non-detects when analyzing for synthetic vitreous fibers on contact surfaces such as desks, floors, 

bookshelves, etc. inside of office buildings (Vallerino et al. 2003). Fiber concentrations in air are usually 

reported as fibers/mL or fibers/cc, although fibers/m3

 or fibers/L are occasionally employed. Fiber 

densities are used to quantify the amount of synthetic vitreous fibers on the surface of objects; these units 

are usually given in fibers/mm2

 (Vallerino et al. 2003). 

Although the PCM method is relatively fast and inexpensive, it does not specifically distinguish between 

the various forms of synthetic vitreous fibers, and it not sensitive to enough to detect fibers possessing 

very small diameters. The resolution of a microscope (the ability to distinguish between two very closely 

spaced objects) is limited by the wavelength of light used for analysis and the numerical aperture of the 

microscope (Hecht 1989). Because PCM uses visible light of approximately 400–700 nm, the maximum 

resolution than can be achieved is about 0.25 μm. Frequently, synthetic vitreous fibers can be 

distinguished from other fibers, like asbestos, based upon their morphology (Switala et al. 1994). Glass 

fibers have clean, well defined, mostly parallel sides, while other fibers such as asbestos usually have 

irregular sides or hair-like appendages emanating from the sides (Switala et al. 1994). The ends of glass 

fibers have three distinctive features that can be useful in their identification: (1) The edges possess a 

clean break that occurs transverse to the fiber length; (2) the ends exhibit a notch-type break; and (3) the 

ends will taper similar to that of a sharpened pencil. Other materials will fan or fry, and therefore, the 

morphology of glass fibers is often distinctive from that of other fiber types. When morphology alone 

cannot distinguish between synthetic vitreous fibers and other fibers, or greater sensitivity is required, 

other microscopic techniques may be employed to augment the analysis. 

Since synthetic vitreous fibers are amorphous substances, polarized light microscopy is often employed to 

distinguish synthetic vitreous fibers from natural minerals with a crystalline structure. In this technique, 
SYNTHETIC VITREOUS FIBERS 209 

7. ANALYTICAL METHODS 

linear polarized radiation is used to illuminate the sample and a second polarizer placed after the sample 

is used to analyze the light that is transmitted as the sample is rotated in various spatial directions 

(NIOSH Method 9002). Amorphous samples like synthetic vitreous fibers have the same refractive index 

in each direction, while anisotropic materials such as asbestos have optical properties that vary with the 

orientation of incident light with the crystallographic axes, and demonstrate a range of refractive indices 

depending both on the propagation direction of light through the substance and on the vibrational plane 

coordinates. 

If improved resolution is required to analyze fibrous samples, transmission electron microscopy (TEM) 

(NIOSH Method 7402) or scanning electron microscopy (SEM) are often employed. Fibers with 

diameters as small as 0.05 and 0.005 μm can be counted by SEM and TEM methods, respectively. In the 

TEM experiment, the wavelength of a 100 KeV electron is 0.0037 nm, which is about 143,000 times 

smaller than the wavelength of light used in PCM. Hence, using electrons for analysis rather than visible 

light photons leads to much better resolution than can be achieved with light microscopy. Identification 

techniques such as energy-dispersive x-ray analysis (EDXA) can be used with SEM and TEM to identify 

fibers on the basis of elemental composition (Spurny 1994). Because EDXA only identifies the elemental 

composition of the fibers, it can only distinguish between organic and inorganic fibers, as well as things 

such as silicate or nonsilicate type fibers. In the TEM experiment, it is also possible to measure the 

diffraction of electrons by crystalline structures that are traversed by the electron beam. This technique 

can be useful to distinguish between crystalline structures and amorphous fibers like synthetic vitreous 

fibers. 

Methods for preparing biological and environmental samples for microscopy are described below. 

7.1 BIOLOGICAL MATERIALS 

The analysis of fibers in biological samples involves digesting the biological material in a strong base 

(e.g., potassium hydroxide) or a powerful oxidant (e.g., hypochlorite). The insoluble residue (including 

the fibrous portion) is collected by ultracentrifugation or filtration, and may be further cleared of 

biological material by ashing. In some cases, biological material may be removed by ashing without prior 

digestion. Residual material is then dispersed and transferred to a suitable support for microscopy. 
SYNTHETIC VITREOUS FIBERS 210 

7. ANALYTICAL METHODS 

Methods for sampling fibrous particles in biological tissue are not standardized and it is often difficult to 

compare results of one laboratory with another (WHO 1988). There is also evidence that indicates that 

digestion of biological materials with potassium hydroxide or sodium hypochlorite can cause substantial 

loss of synthetic vitreous fibers in the samples (McDonald et al. 1990). A review on the methods of 

sampling, analysis, and identification of fibers in lung tissue has been published (Davis et al. 1986). It 

was concluded that low temperature ashing in the presence of nascent oxygen is a superior extraction 

method than chemical digestion alone (Davis et al. 1986). A method for the sampling and identification 

of nonrespirable fibers in the eyes of workers frequently exposed to synthetic vitreous fibers has been 

published (Schneider and Stockholm 1981). In this procedure, mucous threads and dried mucous samples 

were ashed in a low temperature asher and examined by PCM. A correlation was reported between 

synthetic vitreous fibers levels in the eyes and total dust samples in the workplace. The techniques used 

to analyze synthetic vitreous fibers in biological samples are summarized in Table 7-1. 

7.2 ENVIRONMENTAL SAMPLES 

For the analysis of fibers in air, a sample of air is drawn through a filter by a vacuum pump (usually at a 

flow-rate of around 1–2 L/minute), and the fibers retained on the filters are examined microscopically. 

Two types of filters are commonly employed for air sample collection, cellulose ester membrane filters 

(MF) and polycarbonate (Nuclepore) filters (NPF) (Spurny 1994). The NPF is a surface filter that retains 

fibers on the exterior of the filter, while the MF is a spongy depth type filter. The sensitivity of the 

methods depends on the volume of air drawn through the filter, the filtration procedure, and the 

microscopic method employed. Filtration studies have shown that an MF with pore size of 0.8 μm and an 

NPF with a pore size of 0.4 μm are capable of collecting most fibers in the workplace (Spurny 1994). Air 

samples obtained using NPFs can be applied directly for SEM or EDXA analysis without further 

preparation; however, specimen preparation for TEM analysis is more complex. In the workplace, where 

PCM is the standard method, the working range of countable fibers for a short-term sample (15 minutes) 

is around 0.5–0.04 fiber/cc, but may be reduced to 0.001 fiber/cc using an 8-hour sample because a larger 

volume of air is collected (NIOSH 1976). Improvements in filter preparation procedures now allow for 

viewing at higher magnification (1,250x), resulting in a several-fold improvement in sensitivity for these 

fibers (Pang et al. 1989). Recently, detection limits of 1x10-5 f/cc have been obtained using a 12-hour 

sampling procedure (Switala et al. 1994). It is important to keep in mind that only fibers with diameters 

>0.25 μm can be counted by PCM, while fibers with diameters as small as 0.05 and 0.005 μm can be 
SYNTHETIC VITREOUS FIBERS 211 

7. ANALYTICAL METHODS 

Table 7-1. Analytical Methods for Determining Synthetic Vitreous Fibers in 

Biological Samples 

Sample 

matrix Preparation method 

Analytical 

method 

Sample detection 

limit 

Percent 

recovery Reference 

Bronchoalveolar fluid Digestion with sodium 

hypochlorite; membrane 

filter; dry 

PCM No data No data Spurny 1994 

Urine Membrane filtration followed 

by ashing and dispersion in 

1% acetic acid followed by 

nuclepore filtration (0.1 μm) 

TEM No data No data Spurny 1994 

Eye mucous Low temperature ashing PCM No data No data Schneider and 

Stockholm 1981 

Lung tissue Low temperature ashing in a 

plasma asher; filtration with 

0.2 μm nuclepore 

TEM 0.04 μm (diameter) 

0.09 μm (length) 

No data McDonald et al. 

1990 

PCM = phase contrast microscopy; TEM = transmission electron microscopy 
 

 

SYNTHETIC VITREOUS FIBERS 212 

7. ANALYTICAL METHODS 

counted by SEM and TEM methods, respectively (WHO 1988). The techniques used to analyze synthetic 

vitreous fibers in air samples are summarized in Table 7-2. 

While no methods were located for the analysis of synthetic vitreous fibers in water, TEM-based methods 

exist that can quantify asbestos concentrations in water samples, and these methods should also be 

applicable toward the measurement of synthetic vitreous fibers (Brackett et al. 1992; Melton et al. 1978). 

No methods were located for the analysis of asbestos or synthetic vitreous fibers in soil. 

7.3 ADEQUACY OF THE DATABASE 

Section 104(i)(5) of CERCLA, as amended, directs the Administrator of ATSDR (in consultation with the 

Administrator of EPA and agencies and programs of the Public Health Service) to assess whether 

adequate information on the health effects of synthetic vitreous fibers is available. Where adequate 

information is not available, ATSDR, in conjunction with NTP, is required to assure the initiation of a 

program of research designed to determine the health effects (and techniques for developing methods to 

determine such health effects) of synthetic vitreous fibers. 

The following categories of possible data needs have been identified by a joint team of scientists from 

ATSDR, NTP, and EPA. They are defined as substance-specific informational needs that if met would 

reduce the uncertainties of human health assessment. This definition should not be interpreted to mean 

that all data needs discussed in this section must be filled. In the future, the identified data needs will be 

evaluated and prioritized, and a substance-specific research agenda will be proposed. 

7.3.1 Identification of Data Needs 

Methods for Determining Biomarkers of Exposure and Effect. Standardized techniques to 

evaluate the levels of synthetic vitreous fibers in biological tissues do not exist. In general, biological 

tissues are subject to digestion with a strong base or oxidizing agent, followed by ashing. The tissue is 

then analyzed by microscopic examination. A method for the sampling and identification of 

nonrespirable fibers in the eyes of workers frequently exposed to synthetic vitreous fibers has been 

published (Schneider and Stockholm 1981). A data need exists to develop reliable methods to analyze for 

synthetic vitreous fibers in human tissue. 
SYNTHETIC VITREOUS FIBERS 213 

7. ANALYTICAL METHODS 

Table 7-2. Analytical Methods for Determining Synthetic Vitreous Fibers in 

Environmental Samples 

Sample Preparation Analytical Sample Percent Reference 

matrix method method detection limita recovery 

Air Pump air through PCM 0.01 f/cc ±35 ASTM 1988 

filter membrane; 

convert to optically 

transparent gel 

Air Filter with 0.45– NIOSH 7400; 0.003 f/cc No data Jacob et al. 1993; 

1.2 μm cellulose PCM NIOSH 1994a 

ester membrane 

filter 

Air Filter with 0.45– PCM; polarized 1x10-5 f/cc No data Switala et al. 

1.2 μm cellulose light microscopy 1994 

ester membrane 

filter 

Air Filter with 0.45– NIOSH 7402; 0.001 f/cc No data NIOSH 1994a; 

1.2 μm cellulose TEM Spurny 1994 

ester membrane 

filter 

Surfaces Collect samples NIOSH 7400 0.06–0.24 f/mm2 No data Vallarino et al. 

using 12.56 or 

50.24 mm2

 finger2003 

print lifters; transfer 

to microscope slide 

a

Sample detection limits in air are a function of the volume of air collected and thus the sampling time. Detection 

limits on the surface of an object are a function of the number of fibers collected per unit area. 

f/cc = fibers per cubic centimeter; NIOSH = National Institute for Occupational Safety and Health; PCM = phase 

contrast microscopy; TEM = transmission electron microscopy 
 

 

 

SYNTHETIC VITREOUS FIBERS 214 

7. ANALYTICAL METHODS 

Exposure. Uncoated or coated fibers in bronchoalveolar lavage fluid samples or in autopsied or 

surgically resected lung tissue samples are the principal biomarkers of exposure to biopersistent asbestos 

fibers (Agency for Toxic Substances and Disease Registry 2001).1

 However, similar biomarkers to 

identify or quantify human exposure to synthetic vitreous fibers, which are less biopersistent than 

asbestos fibers, have not been developed for routine clinical use. Nevertheless, aluminum-silicate fibers 

with chemical compositions consistent with synthetic vitreous fibers have been detected in human lung 

tissues (McDonald et al. 1990; Roggli 1989; Sébastien et al. 1994) and in bronchoalveolar lavage samples 

(Dumortier et al. 2001). 

Among 1,800 bronchoalveolar samples submitted to a Belgium hospital between 1992 and 1997 for fiber 

analysis, pseudoasbestos bodies were detected in samples from nine patients (0.5%) (Dumortier et al. 

2001). In samples from these nine patients (all of whom had occupational experience with furnaces or 

welding), fibers of composition consistent with refractory ceramic fiber composition were detected in 

42% of core fibers analyzed (Dumortier et al. 2001). Other nonasbestos fibers and asbestos fibers 

accounted for 28% and 30% of the core fibers analyzed in these samples. 

Effect. Epidemiological studies of synthetic vitreous fiber manufacturing workers have not found 

consistent evidence for increased risks of malignant or nonmalignant respiratory or pleural effects, but 

results from animal experiments indicate that repeated inhalation exposure to synthetic vitreous fibers 

may result in pulmonary or pleural fibrosis, lung cancer, or mesothelioma, depending on fiber 

dimensions, fiber durability in the lung, duration of exposure, and exposure levels. 

The chest x-ray is the most common means of detecting the onset of pleural or pulmonary changes that 

may precede or accompany fibrosis (i.e., irreversible scarring of lung or pleural tissue that can lead to 

restricted breathing). The International Labour Office (ILO) established a classification system for 

profusion of opacities in chest x-rays that includes four categories of increasing severity, each with three 

subcategories: 0 (0/-, 0/0, 0/1); 1 (1/0, 1/1, 1/2); 2 (2/1, 2/2, 2/3); and 3 (3/2, 3/3, 3/4) (ILO 1989). The 

American Thoracic Society (1986) recommends that chest x-rays be scored for pleural and pulmonary 

changes separately because of the experience with asbestos-exposed workers indicating that pleural and 

pulmonary fibrosis have differences in “epidemiology, clinical features, and prognosis.” Lung function 

1

 Particles or fibers that are deposited in the lung and are too large to be phagocytized by alveolar macrophages may 

become coated with an iron-rich protein coat. The generic term for these structures is ferruginous bodies. When the 

core fiber is asbestos, the resultant structure is termed an asbestos body (Agency for Toxic Substances and Disease 

Registry 2001). Ferruginous bodies having the appearance of asbestos bodies under light microscopy and a 

nonasbestos core fiber have been termed pseudoasbestos bodies (Dumortier et al. 2001). 
SYNTHETIC VITREOUS FIBERS 215 

7. ANALYTICAL METHODS 

tests are also useful to characterize the development of pulmonary or pleural fibrosis; forced vital capacity 

is diminished with increasing severity of pulmonary or pleural fibrosis. 

Development of sensitive and specific chemical or biochemical tests for synthetic vitreous fibers effects 

would be useful. 

Methods for Determining Parent Compounds and Degradation Products in Environmental 

Media. Methods are available to measure synthetic vitreous fibers in air (Jacob et al. 1993; NIOSH 

1994a; Spurny 1994; Switala et al. 1994). These methods are precise, and are sensitive enough to detect 

levels that are frequently encountered in both occupational and non-occupational settings. No specific 

methods of measuring the levels of synthetic vitreous fibers in other environmental media such as soil, 

water, and sediment exist. Since exposure to synthetic vitreous fibers primarily occurs through inhaling 

air, no data need has been identified at this time. 

7.3.2 Ongoing Studies 

No data were found regarding ongoing studies involving analytical methods for the detection of synthetic 

vitreous fibers. 

SYNTHETIC VITREOUS FIBERS 217 

8. REGULATIONS AND ADVISORIES 

The international, national, and state regulations and guidelines regarding synthetic vitreous fibers in air, 

water, and other media are summarized in Table 8-1. 

The U.S. Department of Health and Human Services, National Toxicology Program (NTP 1998, 2000, 

2002) classified glass wool (respirable size) as reasonably anticipated to be a human carcinogen, based 

on sufficient evidence of carcinogenicity in experimental animals. This assessment was originally 

prepared in 1993–1994 for the 7th Report on Carcinogens (NTP 1994), but has not been updated since 

then in the 8th, 9th, or 10th Reports on Carcinogens (NTP 1998, 2000, 2002). Continuous filament glass, 

rock wool, slag wool, or refractory ceramic fibers were not listed or assessed for carcinogenicity in the 

7th, 8th, 9th, or 10th Report on Carcinogens (NTP 1994, 1998, 2000, 2002). 

The International Agency for Research on Cancer (IARC 2002) concluded that epidemiologic studies 

published since the previous IARC (1988) assessment provided no evidence of increased risks of lung 

cancer or of mesothelioma from occupational exposure during the manufacture of man-made vitreous 

fibers and inadequate evidence overall of any excess cancer risk. IARC (2002) concluded that there was 

(1) sufficient evidence in experimental animals for the carcinogenicity of certain special purpose glass 

fibers and of refractory ceramic fibers; (2) limited evidence in experimental animals for the carcinogenicity of insulation glass wool, rock (stone) wool, and slag wool; and (3) inadequate evidence in 

experimental animals for the carcinogenicity of continuous glass filament and certain newly developed, 

less biopersistent fibers such as X-607 and MMVF34. Insulation glass wool, rock (stone) wool, slag 

wool, and continuous filament glass were classified in Group 3, not classifiable as to carcinogenicity to 

humans because of the inadequate evidence of carcinogenicity in humans and the relatively low biopersistence of these materials. In contrast, refractory ceramic fibers and certain special-purpose glass 

fibers (104 E-glass and 475 glass fibers) not used as insulating materials were classified in Group 2B, 

possibly carcinogenic to humans, because of their relatively high biopersistence. 

The U.S. EPA Integrated Risk Information System (IRIS) (2004) has not classified the potential carcinogenicity of glass wool, continuous filament glass, rock wool, or slag wool, but assigned refractory 

ceramic fibers to Group B2, probable human carcinogen, based on no data on carcinogenicity in humans 

and sufficient evidence of carcinogenicity in animal studies. Currently, EPA is developing a cancer 
 

 

 

 

 

 

 

 

 

 

SYNTHETIC VITREOUS FIBERS 218 

8. REGULATIONS AND ADVISORIES 

Table 8-1. Regulations and Guidelines Applicable to Synthetic Vitreous Fibers 

Agency Description Information References 

INTERNATIONAL 

Guidelines: 

 IARC Carcinogenicity classification 

Insulation glass wool, rock (stone) wool, slag 

wool, and continuous filament glass 

Refractory ceramic fibers and certain specialpurpose glass wools not used as insulating 

materials 

Group 3a

Group 2Bb

 IARC 2002 

 IARC 2002 

NATIONAL 

Regulations and Guidelines: 

a. Air 

ACGIH TLV (8-hour TWA) 

Synthetic vitreous fibers ACGIH 2001

 Continuous filament glass fibers, glass wool 

fibers, rock wool fibers, slag wool fibers, 

special purpose glass fibers 

Continuous filament glass (inhalable fraction) 

1.0 fibers/ccc 

5 mg/m3 

Refractory ceramic fibers 0.2 fibers/ccc 

NIOSH REL (10-hour TWA) 

Fibrous glass dust (fiber glas®, fiberglass, 

glass fibers, and glass wool); fibers ≤3.5 μm in 

diameter and ≥10 μm in length) 

Total fibrous glass dust 

3 fibers/cc 

5 mg/m3 

NIOSH 1992 

Refractory ceramic fibers No data NIOSH 1992

 OSHA PEL (8-hour TWA) 

Fiberglass and mineral wool (glass wool, rock 

wool, and slag wool) 

1.0 fiber/cc 

voluntary 

OSHA 1999 

Synthetic vitreous fibers as an inert or nuisance 

dust 

 OSHA 2001b

 Respirable fraction 

 Total dust 

5 mg/m3

15 mg/m3 

b. Water No data 

c. Food No data 

d. Other 

 ACGIH Carcinogenicity classification 

Synthetic vitreous fibers 

 Continuous filament glass fibers (respirable 

fibers and inhalable fraction) 

Group A4d 

ACGIH 2001
 

 

 

 

 

SYNTHETIC VITREOUS FIBERS 219 

8. REGULATIONS AND ADVISORIES 

Table 8-1. Regulations and Guidelines Applicable to Synthetic Vitreous Fibers 

Agency Description Information References 

NATIONAL (cont.) 

ACGIH Glass wool fibers, rock wool fibers, slag wool 

fibers, and special purpose glass fibers 

Refractory ceramic fibers 

Group A3e 

Group A2f

 EPA Carcinogenicity classification 

Glass wool, continuous filament glass, rock 

wool, and slag wool 

No data IRIS 2002 

Refractory ceramic fibers Group B2g

 IRIS 2002 

Inhalation unit risk No data 

Oral slope factor No data 

NTP Carcinogenicity classification 

Glass wool (respirable size) 

Continuous filament glass, rock wool, slag 

wool, and refractory ceramic fibers 

Reasonably 

anticipated to be a 

human carcinogen 

No datah

NTP 2002 

 NTP 2002 

STATE 

Regulations and Guidelines: 

a. Air No data 

b. Water No data 

c. Food No data 

d. Other No data 

a

Group 3: not classifiable as to carcinogenicity to humans, based on inadequate evidence of carcinogenicity in 

humans and inadequate or limited evidence in experimental animals 

b

Group 2B: possibly carcinogenic to humans, based on limited evidence of carcinogenicity in humans and less than 

sufficient evidence of carcinogenicity in experimental animals 

c

Respirable fibers: length >5 μm; aspect ratio ≥3:1, as determined by the membrane filter method at 400– 

450X magnification (4-mm objective), using phase-contrast illumination. d

Group A4: not classifiable as a human carcinogen 

e

Group A3: confirmed animal carcinogen with unknown relevance to humans 

f

Group A2: suspected human carcinogen, based on limited evidence of carcinogenicity in humans and sufficient 

evidence of carcinogenicity in experimental animals with relevance to humans g

Group B2: probable human carcinogen, based on sufficient evidence of carcinogenicity in animals 

h

Not listed or assessed in the 9th Report on Carcinogens (NTP 2001) 

ACGIH = American Conference of Governmental Industrial Hygienists; EPA = Environmental Protection Agency; 

IARC = International Agency for Research on Cancer; IRIS = Integrated Risk Information System; NIOSH = National 

Institute of Occupational Safety and Health; NTP = National Toxicology Program; OSHA = Occupational Safety and 

Health Administration; PEL = permissible exposure limit; REL = recommended exposure limit; TLV = threshold limit 

value; TWA = time-weighted average 
SYNTHETIC VITREOUS FIBERS 220 

8. REGULATIONS AND ADVISORIES 

assessment for refractory ceramic fibers based on recent multiple-exposure chronic inhalation animal 

bioassays. The assessment is considering the development of quantitative inhalation unit risk estimates 

for refractory ceramic fibers based on the animal tumorigenic responses, but, as of February 2004, the 

assessment was not completed. 

In 1999, a Health and Safety Partnership Program was established as a voluntary workplace safety 

program for workers involved in the manufacture, fabrication, installation, and removal of glass wool, 

rock wool, and slag wool products (Marchant et al. 2002; OSHA 1999). The program was established as 

a result of negotiations between OSHA, the North American Insulation Manufacturers Association, the 

National Insulation Association, and the Insulation Contractors Association of America. The program 

established a voluntary eight-hour time-weighted average (TWA) permissible exposure limit (PEL) of 

1 respirable fiber/cc. Respirable fibers are counted as particles with length >5 μm, diameter <3 μm, and 

aspect ratio ≥3:1. The agreement specifies that when the PEL is exceeded in a workplace (such as when 

insulation is blown into attics or removed), workers will wear NIOSH certified dust respirators. 
 

SYNTHETIC VITREOUS FIBERS 221 

9. REFERENCES 

Aalto M, Heppleston AG. 1984. Fibrogenesis by mineral fibres: An in-vitro study of the roles of the 

macrophage and fibre length. Br J Exp Pathol 65(1):91-99. 

ACGIH. 1992. Fibrous glass dust. American Conference of Government Industrial Hygienists. 

Cincinnati, OH. 

ACGIH. 1998. Asbestos, all forms. American Conference of Government Industrial Hygienists. 

Cincinnati, OH. 

*ACGIH. 2001. Synthetic vitreous fibers. Supplement to documentation of the threshold limit values 

and biological exposure indices. American Conference of Governmental Industrial Hygienists. 

Cincinnati, OH. 

Adachi S, Kawamura K, Takemoto K. 2001. A trial on the quantitative risk assessment of man-made 

mineral fibers by the rat intraperitoneal administration assay using the JFM standard fibrous samples. Ind 

Health 39(2):168-174. 

*Adachi S, Takemoto K, Kimura K. 1991. Tumorigenicity of fine man-made fibers after intratracheal 

administrations to hamsters. Environ Res 54(1):52-73. 

*Adamson IYR, Bakowska J, Bowden DH. 1994. Mesothelial cell proliferation: A nonspecific response 

to lung injury associated with fibrosis. Am J Respir Cell Mol Biol 10:253-258. 

*Adinolfi M. 1985. The development of the human blood-CSF-brain barrier. Dev Med Child Neurol 

27:532-537. 

*Adlercreutz H. 1995. Phytoestrogens: Epidemiology and a possible role in cancer protection. Environ 

Health Perspect Suppl 103(7):103-112. 

Afaq F, Abidi P, Matin R, et al. 1998. Activation of alveolar macrophages and peripheral red blood cells 

in rats exposed to fibers/particles. Toxicol Lett 99:175-182. 

*Agency for Toxic Substances and Disease Registry. 1989. Decision guide for identifying substancespecific data needs related to toxicological profiles; Notice. Federal Register 54(174):37618-37634. 

Agency for Toxic Substances and Disease Registry. 1990. Biomarkers of organ damage or dysfunction 

for the renal, hepatobiliary, and immune systems. Atlanta, GA. Subcommittee on Biomarkers of Organ 

Damage and Dysfunction, Atlanta, GA. 

*Agency for Toxic Substances and Disease Registry. 2001. Toxicological profile for asbestos (Update). 

Department of Health and Human Services, Atlanta, GA. 

Alam W. 1998. Manufactured mineral fibers. In: Hamilton & Hardy's industrial toxicology. St Louis: 

Mosby Publishers, 571-573. 

*Cited in text 
SYNTHETIC VITREOUS FIBERS 222 

9. REFERENCES 

*Albin M, Engholm G, Hallin N, et al. 1998. Impact of exposure to insulation wool on lung function and 

cough in Swedish construction workers. Occup Environ Med 55:661-667. 

Alexander IC, Brown RC, Jubb GA, et al. 1994. Durability of ceramic and novel man-made mineral 

fibers. Environ Health Perspect 102:67-71. 

*Altman PL, Dittmer DS. 1974. Biological handbooks: Biology data book. Vol. III. 2nd ed. 

Bethesda, MD: Federation of American Societies for Experimental Biology, 1987-2008, 2041. 

*American Thoracic Society. 1986. The diagnosis of nonmalignant diseases related to asbestos. Am 

Rev Resp Dis 134:363-368. 

*Andersen A, Langmark F. 1986. Incidence of cancer in the mineral-wool producing industry in 

Norway. Scand J Work Environ Health 12:72-77. 

*Andersen ME, Krishnan K. 1994. Relating in vitro to in vivo exposures with physiologically based 

tissue dosimetry and tissue response models. In: Salem H, ed. Animal test alternatives: Refinement, 

reduction, replacement. New York: Marcel Dekker, Inc., 9- 25. 

*Andersen ME, Clewell HJ III, Gargas ML, et al. 1987. Physiologically based pharmacokinetics and the 

risk assessment process for methylene chloride. Toxicol Appl Pharmacol 87:185-205. 

Antonsson A-B, Runmark S. 1987. Airborne fibrous glass and dust originating from worked reinforced 

plastics. Am Ind Hyg Assoc J 48(8):684-687. 

Ares J. 1990. Exposure to non-asbestos refractory materials: Corrections to fiber counts for comparable 

risk assessment. Bull Environ Contam Toxicol 45:783-788. 

*ASTM. 1988. Standard test method for airborne asbestos concentration in workplace atmospheremethod D 4240-83. In: 1988 annual book of ASTM standards. Vol. 11.03. Atmospheric analysis, 

occupational safety and health. Philadelphia, PA: American Society for Testing and Materials, 300-308. 

Aufderheide M, Riebe-Imre M, Straub M, et al. 1994a. Cellular effects of mineral fibers. In: 

Dungworth DL, Mauderly JL, Oberdorster G, eds. Toxic and carcinogenic effects of solid particles in the 

respiratory tract. Washington, DC: ILSI Press, 575-580. 

Aufderheide M, Riebe-Imre M, Straub M, et al. 1994b. Differences in the biological effects of 

crocidolite asbestos and two glass fibres on epithelial lung cells. Exp Toxicol Pathol 45(8):467-472. 

Balzer JL. 1976. Environmental data; Airborne concentrations found in various operations. 

Occupational exposure to fibrous glass. Proceedings of a symposium sponsored by NIOSH, April 1976. 

*Balzer JL, Cooper WC, Fowler DP. 1971. Fibrous glass-lined air transmission systems: An assessment 

of their environmental effects. Am Ind Hyg Assoc J 32:512-518. 

*Barchowsky A, Lannon BM, Elmore LC, et al. 1997. Increased focal adhesion kinase- and urokinasetype plasminogen activator receptor-associated cell signaling in endothelial cells exposed to asbestos. 

Environ Health Perspect 105:1131-1137. 
SYNTHETIC VITREOUS FIBERS 223 

9. REFERENCES 

*Barnes DG, Dourson M. 1988. Reference dose (RfD): Description and use in health risk assessments. 

Regul Toxicol Pharmacol 8:471-486. 

Baron PA. 1996. Application of the thoracic sampling definition to fiber measurement. Am Ind Hyg 

Assoc J 57(9):820-824. 

Baron PA. 2001. Measurement of airborne fibers: A review. Ind Health 39:39-50. 

*Bayliss DL, Dement JM, Wagoner JK, et al. 1976. Mortality patterns among fibrous glass production 

workers. Ann N Y Acad Sci 271:324-335. 

Beck EG, Holt PF, Manojlovic N. 1972. Comparison of effects on macrophage cultures of glass fibre, 

glass powder, and chrysotile asbestos. Br J Ind Med 29:280-286. 

Bellmann B, Konig H, Muhle H, et al. 1986. Chemical durability of asbestos and of man-made mineral 

fibres in vivo. J Aerosol Sci 17(3):341-345. 

*Bellmann B, Muhle H, Creutzenberg O, et al. 2001. Effects of nonfibrous particles on ceramic fiber 

(RCF1) toxicity in rats. Inhal Toxicol 13(10):877-901. 

Bellmann B, Muhle H, Creutzenberg O, et al. 2003. Calibration study on subchronic inhalation toxicity 

of man-made vitreous fibers in rats. Inhal Toxicol 15:1147-1177. 

*Bellmann B, Muhle H, Kamstrup O, et al. 1994a. Investigation on the durability of man-made vitreous 

fibers in rat lungs. Environ Health Perspect Suppl 102(5):185-189. 

*Bellmann B, Muhle H, Kamstrup O, et al. 1995. Investigation on the biodurability of chemically 

different stone wool fibres. Exp Toxicol Pathol 47(2-3):195-201. 

*Bellmann B, Muhle H, Pott F. 1994b. Investigation of the biodurability and carcinogenicity of different 

man-made mineral fibres. NATO ASI Ser H 85:299-304. 

*Bender JR. 1993. Pulmonary effects of exposure to fine fiberglass: Irregular opacities and small 

airways obstruction. Br J Ind Med 50(4):381. 

Bender JR, Hadley JG. 1994. Glass fiber manufacturing and fiber safety: The producer's perspective. 

Environ Health Perspect 102(Suppl 6):37-40. 

*Bendsoe N, Bjornberg A, Lowhagen G-B, et al. 1987. Glass fibre irritation and protective creams. 

Contact Dermatitis 17(2):69-72. 

*Berger GS. 1994. Epidemiology of endometriosis. In: Berger GS, ed. Endometriosis: Advanced 

management and surgical techniques. New York, NY: Springer-Verlag, 3-7. 

Bermudez E, Mangum JB, Moss OR, et al. 2003. Pleural dosimetry and pathobiological responses in rats 

and hamsters exposed subchronically to MMVF 10a fiberglass. Toxicol Sci 74:165-173. 

*Bernard A, Hermans C. 1997. Biomonitoring of early effects on the kidney or the lung. Sci Total 

Environ 199:205-211. 
SYNTHETIC VITREOUS FIBERS 224 

9. REFERENCES 

Bernstein DM. 1993. An evaluation of the use of an inhalation model versus intraperitoneal injection 

model for the assessment in rats of the carcinogenicity of natural and man-made vitreous fibers. Zentralbl 

Arbeitsmed Arbeitsshutz Prophyl Ergon 43(4):120-128. 

Bernstein DM, Chevalier J, Smith P. 2003. Comparison of calidria chrysotile asbestos to pure tremolite: 

Inhalation biopersistence and histopathology following short-term exposure. Inhal Toxicol 15:1387­

1419. 

*Bernstein DM, Morscheidt C, Grimm H-G, et al. 1996. Evaluation of soluble fibers using the inhalation 

biopersistence model. A nine-fiber comparison. Inhal Toxicol 8:345-385. 

*Bernstein DM, Morscheidt C, Tiesler H, et al. 1995. Evaluation of the biopersistence of commercial 

and experimental fibers following inhalation. Inhal Toxicol 7(7):1031-1058. 

*Bernstein DM, Riego Sintes JM, Ersboell BK, et al. 2001b. Biopersistence of synthetic mineral fibers 

as a predictor of chronic inhalation toxicity in rats. Inhal Toxicol 13(10):823-849. 

*Bernstein DM, Riego Sintes JM, Ersboell BK, et al. 2001a. Biopersistence of synthetic mineral fibers 

as a predictor of chronic intraperitoneal injection tumor response in rats. Inhal Toxicol 13(10):851-875. 

Berrigan D. 2002. Respiratory cancer and exposure to man-made vitreous fibers: A systematic review. 

Am J Ind Med 42:354-362. 

Berry G. 1999. Models for mesothelioma incidence following exposure to fibers in terms of timing and 

duration of exposure and the biopersistence of the fibers. Inhal Toxicol 11:111-130. 

*Bertazzi PA, Zocchetti C, Riboldi L, et al. 1986. Cancer mortality of an Italian cohort of workers in 

man-made glass-fiber production. Scand J Work Environ Health 12(1):65-71. 

Bertrand R, Pezerat H. 1980. Fibrous glass: Carcinogenicity and dimensional characteristics. IARC Sci 

Publ 30:901-911. 

Bignon J. 1983. Lung diseases and non-asbestos fibres. Eur J Respir Dis 64:397-402. 

Bignon J. 1989. Mineral fibres in the non-occupational environment. In: Bignon J, Peto J, Saracci R, 

eds. Non-occupational exposure to mineral fibres. IARC Publication No. 90. Lyon, France. 

Bignon J, Brochard P, Brown R, et al. 1995. Assessment of the toxicity of man-made fibres. A final 

report of a workshop held in Paris, France, 3-4, February 1994. Ann Occup Hyg 39(1):89-106. 

Bignon J, Monchaux G, Chameaud J, et al. 1983. Incidence of various types of thoracic malignancy 

induced in rats by intrapleural injection of 2 mg of various mineral dusts after inhalation of 222Ra. 

Carcinogenesis 4(5):621-628. 

*Bishop K, Ring SJ, Zoltai T, et al. 1985. Identification of asbestos and glass fibers in municipal sewage 

sludges. Bull Environ Contam Toxicol 34:301-308. 

*Bjornberg A. 1985. Glass fiber dermatitis. Am J Ind Med 8(4-5):395-400. 
SYNTHETIC VITREOUS FIBERS 225 

9. REFERENCES 

*Bjornberg A, Lowhagen G-B. 1977. Patch testing with mineral wool (rockwool). Acta Derm Venereol 

(Stockh) 57(3):257-260. 

*Bjornberg A, Lowhagen G-B, Tengberg J-E. 1979c. Does occupational exposure to glass-fibres 

increase the general skin reactivity to irritants? Contact Dermatitis 5(3):175-177. 

*Bjornberg A, Lowhagen G, Tengberg JE. 1979b. Relationship between intensities of skin test reactions 

to glass-fibres and chemical irritants. Contact Dermatitis 5(3):171-174. 

*Bjornberg A, Lowhagen G-S, Tengberg JE. 1979a. Skin reactivity in workers with and without itching 

from occupational exposure to glass fibers. Acta Derm Venereol (Stockh) 59(1):49-54. 

*Boffetta P, Andersen A, Hansen J, et al. 1999. Cancer incidence among European man-made vitreous 

fiber production workers. Scand J Work Environ Health 25(3):222-226. 

*Boffetta P, Sali D, Kolstad H, et al. 1998. Mortality of short-term workers in two international cohorts. 

J Occup Environ Med 40(12):1120-1126. 

*Boffetta P, Saracci R, Andersen A, et al. 1992. Lung cancer mortality among workers in the European 

production of man-made mineral fibers- a Poisson regression analysis. Scand J Work Environ Health 

18(5):279-286. 

*Boffetta P, Saracci R, Andersen A, et al. 1997. Cancer mortality among man-made vitreous fiber 

production workers. Epidemiology 8(3):259-268. 

Bolton RE. 1983. Fibres and fibrogenesis. Eur J Respir Dis 64:403-405. 

Bolton RE, Davis JMG, Donaldson K, et al. 1982. Variations in the carcinogenicity of mineral fibres. 

Ann Occup Hyg 26(1-4):569-582. 

Borm PJA. 2002. Particle toxicology: From coal mining to nanotechnology. Inhal Toxicol 14:311-324. 

Botham SK, Holt PF. 1973. Comparison of effects of glass fibre and glass powder on guinea-pig lungs. 

Br J Ind Med 30:232-236. 

Bottin MC, Vigneron JC, Rousseau R, et al. 2003. Man-made mineral fiber hazardous properties 

assessment using transgenic rodents: Example of glass fiber testing. Inhal Toxicol 15:1017-1027. 

*Brackett KA, Clark PJ, Millette JR. 1992. Method for the analysis of asbestos fibers in water using 

MCE filters. Microscope 40:159-163. 

*Breysse PN, Lees PSJ, Rooney BC. 1999. Comparison of NIOSH Method 7400 A and B counting rules 

for assessing synthetic vitreous fiber exposures. Am Ind Hyg Assoc J 60(4):526-532. 

Breysse PN, Lees PSJ, Rooney BC, et al. 2001. End-user exposures to synthetic vitreous fibers: II. 

Fabrication and installation fabrication of commercial products. Appl Occup Environ Hyg 16:464-470. 

Brochard P, Pairon JC, Bignon J. 1994. The occupational physician's point of view: The model of manmade vitreous fibers. Environ Health Perspect 102:31-36. 
SYNTHETIC VITREOUS FIBERS 226 

9. REFERENCES 

*Brody AR, Roe MW. 1983. Deposition pattern of inorganic particles at the alveolar level in the lungs 

of rats and mice. Am Rev Respir Dis 128(4):724-729. 

Brown RC. 1991. Carcinogenicity of the insulation wools: Reassessment of the IARC evaluation. 

Regul Toxicol Pharmacol 14:12-23. 

Brown RC. 2000. Influence of non-fibrous particles in the animal testing of refractory ceramic fibres. 

In: Rammlmair D, Mederer J, Pentinghaus H, eds. Applied mineralogy: In research, economy, 

technology, ecology and culture. Gottingen, Germany: Balkema Publishers. 

*Brown DM, Beswick PH, Bell KS, et al. 2000. Depletion of glutathione and ascorbate in lung lining 

fluid by respirable fibres. Ann Occup Hyg 44(2):101-108. 

*Brown DM, Beswick PH, Donaldson K. 1999. Induction of nuclear translocation of NF-KB in 

epithelial cells by respirable mineral fibres. J Pathol 189:258-264. 

*Brown DM, Fisher C, Donaldson K. 1998. Free radical activity of synthetic vitreous fibers: Iron 

chelation inhibits hydroxyl radical generation by refractory ceramic fiber. J Toxicol Environ Health A 

53(7):545-561. 

Brown GM, Cowie H, Davis JMG, et al. 1986. In vitro assays for detecting carcinogenic mineral fibres: 

a comparison of two assays and the role of fibre size. Carcinogenesis 7(12):1971-1974. 

*Brown RC, Chamberlain M, Davies R, et al. 1979a. In vitro biological effects of glass fibers. J 

Environ Pathol Toxicol 2(6):1369-1383. 

*Brown RC, Chamberlain M, Skidmore JW. 1979b. In vitro effects of man-made mineral fibres. Ann 

Occup Hyg 22(2):175-179. 

Brown RC, Hoskins JA, Miller K, et al. 1990. Pathogenetic mechanisms of asbestos and other mineral 

fibres. Mol Aspects Med 11(5):325-349. 

Brown RC, Poole A, Turver CJ. 1986. In vitro correlates of mineral dust toxicity. Food Chem Toxicol 

24(6-7):535-538. 

*Brown RC, Sara EA, Hoskins JA, et al. 1992. The effects of heating and devitrification on the structure 

and biological activity of aluminosilicate refractory ceramic fibres. Ann Occup Hyg 36(2):115-129. 

*Brown RC, Sebastien P, Bellmann B, et al. 2000. Particle contamination in experimental fiber 

preparations. Inhal Toxicol 12(3):99-107. 

*Brüske-Hohlfeld I, Moehner M, Pohlabein H, et al. 2000. Occupational lung cancer risk for men in 

Germany: Results from a pooled case-control study. Am J Epidemiol 151(4):384-395. 

*Buchanich JM, Marsh GM, Youk AO. 2001. Historical cohort study of US man-made vitreous fiber 

production workers: V. Tobacco-smoking habits. J Occup Environ Med 43(9):793-802. 

Bunn WB, Bender JR, Hesterberg TW, et al. 1993. Recent studies of man-made vitreous fibers. J Occup 

Med 35(2):101-113. 
 

SYNTHETIC VITREOUS FIBERS 227 

9. REFERENCES 

Bunn WB, Versen RA, Chase GR. 1991. An update on the health effects of man-made vitreous fibers 

and potential fiber exposures. Tappi J June 1991:136-143. 

*Burge PS, Calvert IA, Trethowan WM, et al. 1995. Are the respiratory health effects found in 

manufacturers of ceramic fibres due to the dust rather than the exposure to fibres? Occup Environ Med 

52:105-109. 

Camilucci L, Campopiano A, Casciardi S, et al. 2001. [Exposure to artificial mineral fibers in public 

buildings.] Med Lav 92(1):32-38. (Italian) 

*Carpenter RL, Wilson CL. 1999. The inhalation toxicity of glass fibers- a review of the scientific 

literature. Naval Health Research Center Detachment (Toxicology) (NHRC/TD). 

*Carter CM, Axten CW, Byers CD, et al. 1999. Indoor airborne fiber levels of MMVF in residential and 

commercial buildings. Am Ind Hyg Assoc J 60(6):794-800. 

Carthew P, Edwards RE, Dorman BM, et al. 1995. Intrapleural administration of vitreous high duty 

ceramic fibres and heated devitrified ceramic fibres does not give rise to pleural mesothelioma in rats. 

Hum Exp Toxicol 14(8):657-661. 

Casciardi S, Camppoiano A, Fioravanti F, et al. 2003. [An example of size characterization of synthetic 

vitreous fibers.] Med Lav 94:542-555. (Italian) 

*Casey G. 1983. Sister-chromatid exchange and cell kinetics in CHO-K1 cells, human fibronblasts and 

lymphoblastoid cells exposed in vitro to asbestos and glass fibre. Mutat Res 116:369-377. 

*Chamberlain M, Tarmy EM. 1977. Asbestos and glass fibres in bacterial mutation tests. Mutat Res 

43:159-164. 

*Cheng RT, McDermott HJ, Gia GM, et al. 1992. Exposures to refractory ceramic fiber in refineries and 

chemical plants. Appl Occup Environ Hyg 7(6):361-367. 

Cherrie J, Dodgson J. 1986. Past exposures to airbrone fibers and other potential risk factors in the 

European man-made mineral fiber production industry. Scand J Work Environ Health 12:26-33. 

Cherrie J, Dodgson J, Groat S, et al. 1987. Environmental surveys in the European man-made mineral 

fiber production. Scand J Work Environ Health 12:18-25. 

*Chiazze L, Watkins DK, Fryar C. 1992. A case-control study of malignant and non-malignant 

respiratory disease among employees of a fiberglass manufacturing facility. Br J Ind Med 49:326-331. 

*Chiazze L, Watkins DK, Fryar C, et al. 1993. A case-control study of malignant and non-malignant 

respiratory disease among employees of a fiberglass manufacturing facility II. Exposure assessment. Br 

J Ind Med 50(8):717-725. 

*Chiazze L, Watkins DK, Fryar C. 1995. Adjustment for the confounding effect of cigarette smoking in 

an historical cohort mortality study of workers in a fiberglass manufacturing facility. J Occup Environ 

Med 37(6):744-748. 
 

SYNTHETIC VITREOUS FIBERS 228 

9. REFERENCES 

*Chiazze L, Watkins DK, Fryar C. 1997. Historical cohort mortality study of a continuous filament 

fiberglass manufacturing plant. I. White men. J Occup Environ Med 39(5):432-441. 

*Chiazze L, Watkins DK, Fryar C, et al. 2002. Mortality from non-malignant respiratory disease in the 

fibreglass manufacturing industry. Occup Environ Med 59:369-372. 

*Christensen VR, Eastes W, Hamilton RD, et al. 1993. Fiber diameter distributions in typical MMVR 

wool insulation products. Am Ind Hyg Assoc J 54(5):232-238. 

*Christensen VR, Jensen SL, Guldberg M, et al. 1994. Effect of chemical composition of man-made 

vitreous fibers on the rate of dissolution in vitro at different pHs. Environ Health Perspect 102:83-86. 

*Churg A, Stevens B. 1995. Enhanced retention of asbestos fibers in the airways of human smokers. 

Am J Respir Crit Care Med 151:1409-1413. 

Churg A, Warnock ML, Bensch KG. 1978. Malignant mesothelioma arising after direct application of 

asbestos and fiber glass to the pericardium. Am Rev Respir Dis 118(2):419-424. 

*Churg A, Wright JL, Hobson J, et al. 1992. Effects of cigarette smoke on the clearance of short 

asbestos fibres from the lung and a comparison with the clearance of long asbestos fibres. Int J Exp Path 

73:287-297. 

*Churg A, Wright J, Gilks B, et al. 2000. Pathogenesis of fibrosis produced by asbestos and man-made 

mineral fibers: What makes a fiber fibrogenic? Inhal Toxicol 12:15-26. 

Class P, Deghilage P, Brown RC. 2001. Dustiness of different high-temperature insulation wools and 

refractory ceramic fibres. Ann Occup Hyg 45(5):381-384. 

*Claude J, Frentzel-Beyme R. 1984. A mortality study of workers employed in a German rock wool 

factory. Scand J Work Environ Health 10:151-157. 

*Claude J, Frentzel-Beyme R. 1986. Mortality of workers in a German rock-wool factory-A second look 

with extended follow-up. Scand J Work Environ Health 12:53-60. 

*Clausen J, Netterstrom B, Wolff C. 1993. Lung function in insulation workers. Br J Ind Med 50:252­

256. 

Cleland LG, Vernon-Roberts B, Smith K. 1984. Fibre glass induced synovitis. Ann Rheum Dis 43:530­

534. 

*Clewell HJ III, Andersen ME. 1985. Risk assessment extrapolations and physiological modeling. 

Toxicol Ind Health 1(4):111-131. 

Clouter A, Houghton CE, Bowskill CA, et al. 1996. An in vitro/in vivo study into the short term effects 

of exposure to mineral fibres. Exp Toxicol Pathol 48:484-486. 

Clupper DC, Gough JE, Hall MM, et al. 2003. In vitro bioactivity of S520 glass fibers and initial 

assessment of osteoblast attachment. J Biomed Mater Res 67A:285-294. 
 

SYNTHETIC VITREOUS FIBERS 229 

9. REFERENCES 

*Colborn T, Clement C, eds. 1992. Chemically-induced alterations in sexual and functional 

development: The wildlife-human connection. In: Advances in modern environmental toxicology. Vol. 

XXI, Princeton, NJ: Princeton Scientific Publishing. 

Collier CG, Morris KJ, Launder KA, et al. 1994. The behavior of glass fibers in the rat following 

intraperitoneal injection. Regul Toxicol Pharmacol 20:S89-S103. 

Collier CG, Morris KJ, Launder KA, et al. 1995. The durability and distribution of glass fibres in the rat 

following intra-peritoneal injection. Ann Occup Hyg 39(5):699-704. 

Corn M, Hammad Y, Whittier D, et al. 1976. Employee exposure in airborne fiber and total particulate 

matter in two mineral wool facilities. Environ Res 12:59-74. 

*Cowie HA, Wild P, Beck J, et al. 2001. An epidemiological study of the respiratory health of workers 

in the European refractory ceramic fibre industry. Occup Environ Med 58:800-810. 

Cullen RT, Miller BG, Clark S, et al. 2002. Tumorigenicity of cellulose fibers injected into the rat 

peritoneal cavity. Inhal Toxicol 14:685-703. 

*Cullen RT, Searl A, Buchanan D, et al. 2000. Pathogenicity of a special-purpose glass microfiber (E 

Glass) relative to another glass microfiber and amosite asbestos. Inhal Toxicol 12(10):959-977. 

Cummings KM, Hastrup JL, Streck RJ, et al. 2000a. Correspondence Re: Cummings et al., consumer 

perception of risk associated with filters contaminated with glass fibers. Cancer Epidemiol Biomarkers 

Prev 10(4):417-418. 

Cummings KM, Hastrup JL, Swedrock T, et al. 2000b. Consumer perception of risk associated with 

filters contaminated with glass fibers. Cancer Epidemiol Biomarkers Prev 9(9):977-979. 

*Dai YT, Yu CP. 1998. Alveolar deposition of fibers in rodents and humans. J Aerosol Med 11(4):247­

258. 

Davies R. 1980. The effect of mineral fibres on macrophages. In: Wagner JC, Davis W, eds. 

Biological effects of mineral fibres. IARC Scientific Publication No. 30. Lyon, France, 419-425. 

Davies L, Cherrie JW. 1992. Airborne fiber concentrations in a glass continuous filament factory. Ann 

Occup Hyg 36(6):609-627. 

Davis JMG. 1972. The fibrogenic effects of mineral dusts injected into the pleural cavity of mice. Br J 

Exp Pathol 53:190-201. 

Davis JMG. 1986. A review of experimental evidence for the carcinogenicity of man-made vitreous 

fibers. Scand J Work Environ Health 12:12-17. 

Davis JA, Kalinowski MR. 1989. Development of LM/SEM/TEM methods for the quantitative analysis 

of airborne glass fiber levels. In: Russell PE, ed. 29th annual meeting of the Microbeam Analysis 

Society. San Francisco, CA: San Francisco Press, Inc., 427-428. 
SYNTHETIC VITREOUS FIBERS 230 

9. REFERENCES 

*Davis JMG, Addison RE, Bolton K, et al. 1984. The pathogenic effects of fibrous ceramic aluminum 

silicate glass administered to rats by inhalation and peritoneal injection. In: Biological effects of manmade mineral fibers. Proceedings of a WHO/IARC Conference, Vol. 2, Copenhagen, Denmark, April 20­

22, 1982, 303-322. 

*Davis JMG, Brown DM, Cullen RT, et al. 1996. A comparison if methods of determining and 

predicting the pathogenicity of mineral fibers. Inhal Toxicol 8(8):747-770. 

*Davis JMG, Gylseth B, Morgan A. 1986. Assessment of mineral fibres from human lung tissue. 

Thorax 41:167-175. 

Dement JM. 1975. Environmental aspects of fibrous glass production and utilization. Environ Res 

9:295-312. 

Denizeau F, Marion M, Chevalier G, et al. 1985. Absence of genotoxic effect of nonasbestos mineral 

fibers. Cell Biol Toxicol 1(2):23-32. 

Deren G. 1995. Refractory-ceramic-fiber furnace linings. Am Ceram Soc Bull 74(5):65-68. 

DeVuyst P, Dumortier P, Swaen GMH, et al. 1995. Respiratory health effects of man-made vitreous 

(mineral) fibres. Eur Resp J 8(12):2149-2173. 

Dodgson J, Ottery J, Cherrie JW, et al. 1980. Fibre concentrations and size distributions of airborne 

fibres in several European man-made mineral fibre plants. IARC Sci Publ 30:913-925. 

Donaldson K. 1994. Biological activity of respirable industrial fibres treated to mimic residence in the 

lung. Toxicol Lett 72(1-3):299-305. 

Donaldson K. 2001. The toxicology of respirable industrial fibres: An overview. Toxicol Lett 123:11. 

Donaldson K, Tran CL. 2002. Inflammation caused by particles and fibers. Inhal Toxicol 14:5-27. 

Donaldson K, Brown DM, Miller BG, et al. 1995a. Bromo-deoxyuridine (BRDU) uptake in the lungs of 

rats inhaling amosite asbestos or vitreous fibers at equal airborne fibre concentrations. Exp Toxicol 

Pathol 47(2-3):207-211. 

*Donaldson K, Gilmour PS, Beswick PH. 1995c. Supercoiled plasmid DNA as a model target for 

assessing the generation of free radicals at the surface of fibres. Exp Toxicol Pathol 47(4):235-237. 

*Donaldson K, Hill IM, Beswick PH. 1995b. Superoxide anion release by alveolar macrophages 

exposed to respirable industrial fibres: modifying effect of fibre opsonisation. Exp Toxicol Pathol 

47(4):229-231. 

*Dopp E, Schiffmann D. 1998. Analysis of chromosomal alteration induced by asbestos and ceramic 

fibers. Toxicol Lett 96:155-162. 

Dopp E, Nebe B, Hahnel C, et al. 1995. Mineral fibers induce apoptosis in Syrian hamster embryo 

fibroblasts. Pathobiology 63:213-221. 
SYNTHETIC VITREOUS FIBERS 231 

9. REFERENCES 

*Dopp E, Schuler M, Schiffmann D, et al. 1997. Induction of micronucleai, hyperdiploidy and 

chromosomal breakage affecting the centri/pericentric regions of chromosomes 1 and 9 in human 

amniotic fluid cells after treatment with asbestos and ceramic fibers. Mutat Res 377:77-87. 

Dörger M, Allmeling A-M, Neuber A, et al. 1997. Interspecies comparison of rat and hamster alveolar 

macrophage antioxidative and oxidative capacity. Environ Health Perspect 105:1309-1312. 

*Dörger M, Munzing S, Allmeling A-M, et al. 2000. Comparison of the phagocytic response of rat and 

hamster alveolar macrophages to man-made vitreous fibers in vitro. Hum Exp Toxicol 19(11):635-640. 

*Dörger M, Munzing S, Allmeling AM, et al. 2001. Differential responses of rat alveolar and peritoneal 

macrophages to man-made vitreous fibers in vitro. Environ Res 85:207-214. 

*Driscoll KE. 1996. Effects of fibres on cell proliferation, cell activation and gene expression. IARC 

Sci Publ 140:73-96. 

*Driscoll KE, Carter JM, Hassenbein DG, et al. 1997. Cytokines and particle-induced inflammatory cell 

recruitment. Environ Health Perspect 105(5):1159-1164. 

*Dufresne A, Perrault G, Yamato H, et al. 1999. Clearance of man made mineral fibres from the lungs 

of sheep. Occup Environ Med 56:684-690. 

*Dumortier P, Broucke I, DeVuyst P. 2001. Pseudoasbestos bodies and fibers in bronchoalveolar lavage 

of refractory ceramic fiber users. Am J Respir Crit Care Med 164(3):499-503. 

*Eastes W, Hadley JG. 1995. Dissolution of fibers inhaled by rats. Inhal Toxicol 7:179-196. 

*Eastes W, Hadley JG. 1996. A mathematical model of fiber carcinogenicity and fibrosis in inhalation 

and intraperitoneal experiments in rats. Inhal Toxicol 8:323-343. 

Eastes W, Hadley JG. 2001. Comment on "Long man-made fibers and lung cancer risk.” Regul Toxicol 

Pharmacol 33(2):268. 

*Eastes W, Morris KJ, Morgan A, et al. 1995. Dissolution of glass fibers in the rat lung following 

intratracheal instillation. Inhal Toxicol 7:197-213. 

*Eastes W, Potter RM, Hadley JG. 2000. Estimating in vitro glass fiber dissolution rate from 

composition. Inhal Toxicol 12(4):269-280. 

*Ellenhorn MJ. 1997. Man-made mineral fibers (MMMF). In: Ellenhorn’s medical toxicology, 1515­

1518. 

Engholm G, Englund A, Fletcher AC, et al. 1987. Respiratory cancer incidence in Swedish construction 

workers exposed to man-made mineral fibres and asbestos. Ann Occup Hyg 31(48):663-675. 

*Engholm G, vonSchmalensee G. 1982. Bronchitis and exposure to man-made mineral fibres in nonsmoking construction workers. Eur J Respir Dis 118:73-78. 
SYNTHETIC VITREOUS FIBERS 232 

9. REFERENCES 

England EC, Carlton GN, Krevonick PL. 2000. The impact of ventilation systems on worker exposures 

during advanced composite material and fiberglass repair operations on military aircraft. Appl Occup 

Environ Hyg 15(5):391-396. 

*Enterline PE. 1990. Role of manmade mineral fibres in the causation of cancer. Br J Ind Med 47:145­

145. 

*Enterline PE, Henderson V. 1975. The health of retired fibrous glass workers. Arch Environ Health 

30:113-116. 

*Enterline PE, Marsh GM, Esmen NA. 1983. Respiratory disease among workers exposed to man-made 

mineral fibers. Am Rev Respir Dis 128(1):1-7. 

*Enterline PE, Marsh GM, Henderson V, et al. 1987. Mortality update of a cohort of U.S. man-made 

mineral fibre workers. Ann Occup Hyg 31(4B):625-656. 

*Environment Canada. 1993. Mineral fibres (man-made vitreous fibres). Priority Substances List 

Assessment Report. 

*EPA. 1980. Man-made vitreous fibers and health. In: Proceedings of the National Workshop on 

Substitutes for Asbestos. U.S. Environmental Protection Agency. EPA560380001. 

*EPA. 1990. Interim methods for development of inhalation reference concentrations. Washington, DC: 

U.S. Environmental Protection Agency, Office of Health and Environmental Assessment, Office of 

Research and Development, Environmental Criteria and Assessment Office. EPA600890066A. 

*EPA. 1992. ARARs fact sheet: Compliance with the clean air act and associated air quality 

requirements. Washington, DC: U.S. Environmental Protection Agency, Office of Solid Waste and 

Emergency Response. EPA9234222FS. 

*EPA. 1995. Reportable Quantity Adjustments; final rule. Fed Regist 60(112):30925. 

*EPA. 1997. Special report on environmental endocrine disruption: An effects assessment and analysis. 

Washington, DC: U.S. Environmental Protection Agency, Risk Assessment Forum. EPA630R96012. 

*Ernst P, Shapiro S, Dales RE, et al. 1987. Determinants of respiratory symptoms in insulation workers 

exposed to asbestos and synthetic mineral fibres. Br J Ind Med 44:90-95. 

*Esmen NA, Erdal S. 1990. Human occupational and nonoccupational exposure to fibers. Environ 

Health Perspect 88:277-286. 

*Esmen NA, Corn M, Hammad YY, et al. 1979a. Exposure of employees to man-made mineral fibers: 

Ceramic fiber production. Environ Res 19:265-278. 

*Esmen N, Corn M, Hammad Y, et al. 1979b. Summary of measurements of employee exposure to 

airborne dust and fiber in sixteen facilities producing man-made mineral fibers. Am Ind Hyg Assoc J 

40:108-117. 

*Esmen NA, Hammad YY, Corn M, et al. 1978. Exposure to employees to man-made mineral fibers: 

Mineral wool production. Environ Res 15:262-277. 
SYNTHETIC VITREOUS FIBERS 233 

9. REFERENCES 

Estes W, Morris KJ, Morgan A, et al. 1995. Dissolution of glass fibers in the rat lung following 

intratracheal instillation. Inhal Toxicol 7(2):197-213. 

*Eun HC, Lee HG, Paik NW. 1991. Patch test responses to rockwool of different diameters evaluated by 

cutaneous blood flow measurement. Contact Dermatitis 24(4):270-273. 

Everest Consulting Associates. 1996. Particulate-to-fiber ratios and fiber size distributions in the RCC 

maximum and tolerated dose (MTD) study and in the workplace. Presented to the U.S. Environmental 

Protection Agency. Prepared by Everest Consulting Associates, Cranbury, NJ. 

*Everitt J, Bermudez E, Mangum J, et al. 1994. Acute pleural response of hamsters and rats to inhaled 

ceramic fibers. In: Dungworth DL, Mauderly JL, Oberdorster G, eds. Toxic and carcinogenic effects of 

solid particles in the respiratory tract. Washington DC: ILSI Press, 599-602. 

*Everitt JI, Gelzleichter TR, Bermudez E, et al. 1997. Comparison of pleural responses of rats and 

hamsters to subchronic inhalation of refractory ceramic fibers. Environ Health Perspect 105:1209-121. 

Fallentin B, Kamstrup O. 1993. Simulation of past exposure in slag wool production. Ann Occup Hyg 

37(4):419-433. 

Faux SP, Houghton CE, Hubbard A, et al. 2001. Increased expression of epidermal growth factor 

receptor in rat pleural mesothelial cells correlates with carcinogenicity of mineral fibres. Carcinogenesis 

12(12):2275-2280. 

Fayerweather WE, Bender JR, Hadley JG, et al. 1997. Quantitative risk assessment for a glass fiber 

insulation product. Regul Toxicol Pharmacol 25:103-120. 

Fayerweather WE, Eastes W, Cereghini F, et al. 2002. Quantitative risk assessment of durable glass 

fibers. Inhal Toxicol 14:553-568. 

*FEDRIP. 2002. Federal Research in Progress Database. National Technical Information Service, 

Springfield, VA. 

*Feron VJ, Scherrenberg PM, Immel HR, et al. 1985. Pulmonary response of hamsters to fibrous glass: 

chronic effects of repeated intratracheal instillation with or without benzo[a]pyrene. Carcinogenesis 

6:1495-1499. 

*Fisher AA. 1982. Fiberglass vs mineral wool (rockwool) dermatitis. Cutis 29:412-513. 

*Fisher BK, Warkentin JD. 1969. Fiber glass dermatitis. Arch Dermatol 99:717-719. 

*Fitzer E, Kleinholz R, Tiesler H, et al. 1988. Fibers, synthetic inorganics. In: Gerhartz W, Yamamoto 

YS, Elvers B, et al., eds. Ullmann's encyclopedia of industrial chemistry, 1-66. 

Fogel P, Morsheidt C, Hanton D, et al. 1998. A formula for predicting the tumor incidence in 

intraperitoneal experiments with mineral fibers. Inhal Toxicol 10:875-893. 

*Fomon SJ. 1966. Body composition of the infant: Part I: The male "reference infant." In: Falkner F, 

ed. Human development. Philadelphia, PA: WB Saunders, 239-246. 
SYNTHETIC VITREOUS FIBERS 234 

9. REFERENCES 

*Fomon SJ, Haschke F, Ziegler EE, et al. 1982. Body composition of reference children from birth to 

age 10 years. Am J Clin Nutr 35:1169-1175. 

Forget G, Lacroix MJ, Brown RC, et al. 1986. Response of perifused alveolar macrophages to glass 

fibers: Effect of exposure duration and fiber length. Environ Res 39:124-135. 

*Forrester BG. 1997. Reactive airway dysfunction syndrome: Occurrence after exposure to a refractory 

ceramic fiber-phosphoric acid binder mixture. South Med J 90(4):447-450. 

Fowler DP, Balzer JL, Cooper WC. 1971. Exposure of insulation workers to airborne fibrous glass. Am 

Ind Hyg Assoc J 32(2):86-91. 

Foy JWD, Collier C, Swauger JE. 2003. A comparison of mathematical methods for the determination 

of in vitro dissolution constants for glass fibers. Inhal Toxicol 15:167-179. 

*Fraire AE, Greenberg SD, Spjut HJ, et al. 1994. Effect of fibrous glass on rat pleural mesothelium. Am 

J Respir Crit Care Med 1509:521-527. 

*Friar JJ, Phillips AM. 1989. Exposure to man-made mineral fibres. In: Bignon J, Peto J, Saracci R, 

eds. Non-occupational exposure to mineral fibres. IARC Scientific Publication No. 90. Lyon, France, 

299-303. 

Friemann J, Muller KM, Pott F. 1990. Mesothelial proliferation due to asbestos and man-made fibres. 

Experimental studies on rat omentum. Pathol Res Pract 186(1):117-123. 

Fujoino A, Hori H, Higashi T, et al. 1995. In-vitro biological study to evaluate the toxic potentials of 

fibrous materials. Int J Occup Environ Health 1:21-28. 

Fustinoni S, Colosio C, Colombi A, et al. 1998. Albumin and hemoglobin adducts as biomarkers of 

exposure to styrene in fiberglass-reinforced-plastics workers. Int Arch Occup Environ Health 70:35-41. 

*Gantner BA. 1986. Respiratory hazard from removal of ceramic fiber insulation from high temperature 

industrial furnaces. Am Ind Hyg Assoc J 47(9):530-534. 

*Gao H, Brick J, Ong S-h, et al. 1997. Selective hyperexpression of c-jun oncoprotein by glass fiberand silica-transformed BALB/c-3T3 cells. Cancer Lett 112(1):65-69. 

*Gao HG, Whong W-Z, Jones WG, et al. 1995. Morphological transformation induced by glass fibers in 

BALB/c-3T3 cells. Teratog Carcinog Mutagen 15(2):63-71. 

Gardner IT, Uff JS. 1978. "Blue bodies" in a case of cryptogenic fibrosing alveolitis (desquamative 

type)- an ultra-structural study. Thorax 33:806-813. 

Gardner MJ, Magnani C, Pannett B, et al. 1988. Lung cancer among glass fibre production workers: a 

case-control study. Br J Ind Med 45(9):613-618. 

*Gardner MJ, Winter PD, Pannett B, et al. 1986. Mortality study of workers in the man-made mineral 

fiber production industry in the UK. Scand J Work Environ Health 12:85-93. 
 

SYNTHETIC VITREOUS FIBERS 235 

9. REFERENCES 

*Gaudichet A, Petit G, Billon-Galland MA, et al. 1989. Levels of atmospheric pollution by man-made 

fibres in buildings. In: Bignon J, Peto J, Saracci R, eds. Non-occupational exposure to mineral fibres. 

International Agency for Research on Cancer. IARC Scientific Publication No. 90. Lyon, France, 291­

298. 

Geiser M, Matter M, Maye I, et al. 2003. Influence of airspace geometry and surfactant on the retention 

of man-made vitreous fibers (MMVF 10a). Environ Health Perspect 111(7):895-901. 

*Gelzleichter TR, Bermudez E, Mangum JB, et al. 1996a. Pulmonary and pleural responses in Fischer 

344 rats following short-term inhalation of a synthetic vitreous fiber. I. Quantitation of lung and pleural 

fiber burdens. Fundam Appl Toxicol 30(1):31-38. 

*Gelzleichter TR, Bermudez E, Mangum JB, et al. 1996b. Pulmonary and pleural responses in Fischer 

344 rats following short-term inhalation of a synthetic vitreous fiber (II) Pathobiologic responses. 

Fundam Appl Toxicol 30(1):39-46. 

*Gelzleichter TR, Bermudez E, Mangum JB, et al. 1999. Comparison of pulmonary and pleural 

responses of rats and hamsters to inhaled refractory ceramic fibers. Toxicol Sci 49(1):93-101. 

*Gelzleichter TR, Mangum JB, Vermudez E, et al. 1996c. Pulmonary and pleural leukocytes from F344 

rats produce elevated levels of fibronectin following inhalation of refractory ceramic fibers. Exp Toxicol 

Pathol 48(6):487-489. 

*Gibbs AR, Pooley FD, Griffiths DM, et al. 1996. A histopathological and mineralogical study of lung 

tissues from workers engaged in glass wool manufacture. In: Sixth international meeting on the 

toxicology of natural and man-made fibrous and non-fibrous particles: Lake Placid, NY Spetember 

15-18, 1996. 157. 

*Gilmour PS, Beswick PH, Brown DM, et al. 1995. Detection of surface free radical activity of 

respirable industrial fibres using supercoiled phiX174 plasmid DNA. Carcinogenesis 16(12):2973-2979. 

*Gilmour PS, Brown DM, Beswick PH, et al. 1997. Free radical activity of industrial fibers: Role of 

iron in oxidative stress and activation of transcription factors. Environ Health Perspect Suppl 

105(5):1313-1317. 

*Giwercman A, Carlsen E, Keiding N, et al. 1993. Evidence for increasing incidence of abnormalities of 

the human testis: A review. Environ Health Perspect Suppl 101(2):65-71. 

Glass LR, Brown RC, Hoskins JA. 1995. Health effects of refractory ceramic fibres: scientific issues 

and policy considerations. Occup Environ Med 52(7):433-440. 

*GMIC. 2002. Overview of the U.S. glass industry. Glass Manufacturing Industry Council. 

http://www.gmic.org/. May 07, 2002. 

Goldberg MS, Parent ME, Siemiatycki J. 2001. A case-control study of the relationship between the risk 

of colon cancer in men and exposures to occupational agents. Am J Ind Med 39:531-546. 

*Goldfrank LR. 1998. The pathophysiologic basis of medical toxicology. Part C. In: Goldfrank’s 

toxicologic emergencies, 482. 
 

SYNTHETIC VITREOUS FIBERS 236 

9. REFERENCES 

Goldsmith JR. 1986. Comparative epidemiology of men exposed to asbestos and man-made mineral 

fibers. Am J Ind Med 10(5-6):543-552. 

*Goldsmith JR, Goldsmith DF. 1993. Fiberglass or silica exposure and increased nephritis or ESRD 

(end-stage renal disease). Am J Ind Med 23:873-881. 

*Goldstein B, Rendall REG, Webster I. 1983. A comparison of the effects of exposure of baboons to 

crocidolite and fibrous-glass dusts. Environ Res 32:344-359. 

Gradon L, Podgorski A. 1992. Experimental study on fibrous particle deposition in the human nasal cast. 

J Aerosol Sci 23:S469-S472. 

Greim H, Brinkmann B, Pohlenz-Michel C, et al. 2000. The necessity of developing new criteria for 

carcinogen classification of fibers by the MAK commission. Inhal Toxicol 12:419-425. 

*Greim H, Brom P, Schins R, et al. 2001. Toxicity of fibers and particles-report of the workshop held in 

Munich, Germany, 26-27 October 2000. Inhal Toxicol 13(9):737-754. 

Greim HA, Ziegler-Skylakakis K. 1997. Strategies for setting occupational exposure limits for particles. 

Environ Health Perspect 105:1357-1361. 

Griffis LC, Pickerell JA, Carpenter RL, et al. 1983. Deposition of crocidolite asbestos and glass 

microfibers inhaled by the beagle dog. Am Ind Hyg Assoc J 44(3):216-222. 

Grimm HG, Bernstein DM, Attia M, et al. 2002. Experience from a long-term carcinogenicity study with 

intraperitoneal injection of biosoluble synthetic mineral fibers. Inhal Toxicol 14:855-882. 

*Gross P. 1976. The biologic categorization of inhaled fiber glass dust. Arch Environ Health 31:101­

107. 

*Gross P. 1981. Consideration of the aerodynamic equivalent diameter of respirable mineral fibers. Am 

Ind Hyg Assoc J 42(6):449-452. 

Gross P, Stanton MF. 1973. Tumors of the pleura induced with asbestos and fibrous glass. J Natl 

Cancer Inst 51(1):315-319. 

Gross P, Davis JMG, Harley RA, et al. 1973. Lymphatic transport of fibrous dust from the lungs. J 

Occup Med 15(3):186-189. 

Gross P, deTreville RTP, Cralley LJ. 1968. Pulmonary ferruginous bodies. Developed in response to 

filamentous dusts and a method of isolation and concentration. Arch Pathol 85:539-546. 

Gross P, deTreville RTP, Cralley LJ, et al. 1970. The pulmonary response to fibrous dusts of diverse 

compositions. Am Ind Hyg Assoc J 31:125-132. 

Gross P, Harley RA, Davis JMG, et al. 1974a. Mineral fiber content of human lungs. Am Ind Hyg 

Assoc J 35(3):148-151. 

Gross P, Harley RA, Swinburne LM, et al. 1974b. Ingested mineral fibers. Do they penetrate tissue or 

cause cancer? Arch Environ Health 29:341-347. 
SYNTHETIC VITREOUS FIBERS 237 

9. REFERENCES 

Gross P, Kaschak M, Tolker EB, et al. 1970. The pulmonary reaction to high concentrations of fibrous 

glass dust. Arch Environ Health 20:696-704. 

Gross P, Theodos PA, Murphy RLH. 1976. The pulmonary response to fiberglass dust- Report to the 

Committee on Environmental Health. American College of Chest Physicians. Chest 69(2):216-219. 

Gross P, Tuma J, DeTrebille RTP. 1971. Lungs of workers exposed to fiber glass. Arch Environ Health 

23:67-76. 

Gross P, Westrick ML, Schrenk HH, et al. 1956. The effects of a synthetic ceramic fiber dust upon the 

lungs of rats. AMA Arch Ind Health 13(2):161-166. 

Guldberg M, Jensen SL, Knudsen T, et al. 2002. High-alumina low-silica HT stone wool fibers: A 

chemical compositional range with high biosolubility. Regul Toxicol Pharmacol 35:217-226. 

Gulumian M, Van Wyk JA. 1987. Hydroxyl radical production in the presence of fibres by a fenton-type 

reaction. Chem Biol Interact 62:89-97. 

*Gustavsson P, Plato N, Axelson O, et al. 1992. Lung cancer risk among workers exposed to man-made 

mineral fibers (MMMF) in the Swedish prefabricated house industry. Am J Ind Med 21(6):825-834. 

Gutknecht MHG. 1999. [Results of workplace exposure measurements of refractory ceramic fibers.] 

Geharstoffe Reinhalt Luft 59(5):171-177. (German) 

*Guzelian PS, Henry CJ, Olin SS, eds. 1992. Similarities and differences between children and adults: 

Implications for risk assessment. Washington, DC: International Life Sciences Institute Press. 

*Hall GS, Rice CH, Lockey JE, et al. 1997. A comparison of exposures to refractory ceramic fibres over 

multiple work shifts. Ann Occup Hyg 41(5):555-560. 

Hamilton RD, Miiler WC, Christensen DR, et al. 1994. Characterization of exposure and dose of man 

made vitreous fiber in experimental studies. Environ Health Perspect 102:109-112. 

Hammad YY, Attieh B. 1989. Pulmonary deposition of MMMF. J Aerosol Sci 20(8):1329-1332. 

Hammad YY, Atieh B. 1994. Long-term clearance of ceramic fibers from guinea pig lungs. In: 

Dungworth DL, Mauderly JL, Oberdorster G, eds. Toxic and carcinogenic effects of solid particles in the 

respiratory tract. Washington, DC: ILSI Press, 477-449. 

Hammad YY, Atieh B. 1995. Long-term clearance of ceramic fibers from guinea-pig lungs. Exp 

Toxicol Pathol 47:192-194. 

Hammad Y, Diem J, Craighead J, et al. 1982. Deposition of inhaled man made mineral fibres in the 

lungs of rats. Ann Occup Hyg 26(1):179-187. 

Hansen ES. 2002. Comments on a nested case-control study of lung cancer among European rock and 

slag wool production workers. Int J Occup Environ Health 8:281-283. 
 

 

SYNTHETIC VITREOUS FIBERS 238 

9. REFERENCES 

*Hansen E, Rasmussen F, Hardt F, et al. 1999. Lung function and respiratory health of long-term fiberexposed stonewool factory workers. Am J Respir Crit Care Med 160(2):466-472. 

Hansen J, Boffetta P, Anderson A, et al. 1997. Comparison of information on occupation and lifestyle 

habits obtained from European man-made vitreous fibre production workers and their relatives. Int J 

Epidemiol 26(5):1009-1016. 

Hanton DY, Furtak H, Grimm HG. 1998. Preparation and handling conditions of MMVF for in-vivo 

experiments. Aerosol Sci Technol 29(5):449-456. 

*Haratake J, Yamato H, Hori H, et al. 1995. Histopathologic examinations of rats treated by chronic 

inhalation exposures to glass fibers. Inhal Toxicol 7:343-352. 

*Hart GA, Kathman LM, Hesterberg TW. 1994. In vitro cytotoxicity of asbestos and man-made vitreous 

fibers: Roles of fiber length, diameter and composition. Carcinogenesis 15(5):971-977. 

*Hart GA, Newman MM, Bunn WB, et al. 1992. Cytotoxicity of refractory ceramic fibres to Chinese 

hamster ovary cells in culture. Toxicol in Vitro 6(4):317-326. 

Hashish AH, Fleming JS, Conway J, et al. 1998. Lung deposition of particles by airway generation in 

healthy subjects: three-dimensional radionuclide imaging and numerical model prediction. J Aerosol Sci 

29(1/2):205-215. 

*HazDat. 2004. Agency for Toxic Substances and Disease Registry (ATSDR), Atlanta, GA. 

http://www.atsdr.cdc.gov/hazdat.html. January 12, 2004. 

*Hecht E. 1989. Optics. Second edition. Spatz B, ed. Reading, MA: Addison-Wesley Publishing 

Company, Inc., 191-192. 

Heise H, Mattheus A. 1971. [Skin reactions to insulators: I. Epicutaneous testing of mineral fibers.] 

Dermatol Monatsschr 157(1):52-61. (German) 

Heise H, Mattheus A. 1971. [Skin reactions to insulators: II. Relationships to frequent allergens.] 

Dermatol Monatsschr 157(1):62-67. (German) 

*Heisel EB, Hunt FE. 1968. Further studies in cutaneous reactions to glass fibers. Arch Environ Health 

17:705-711. 

*Hesterberg TW, Barrett JC. 1984. Dependence of asbestos-and mineral dust-induced transformation of 

mammalian cells in culture on fiber dimension. Cancer Res 44:2170-2180. 

Hesterberg TW, Chase GR. 1995. Commentary on "Fibrous glass and lung cancer". Letter to the editor. 

Am J Ind Med 30:111-112. 

Hesterberg TW, Hart GA. 1994. A comparison of human exposures to fiberglass with those used in a 

recent rat chronic inhalation study. Regul Toxicol Pharmacol 20:S35-S46. 

*Hesterberg TW, Hart GA. 1998. Health and safety aspects of fiber glass. Nonwoven Conference and 

Trade Fair, St. Petersburg, FL, March 9-11, 1998. Atlanta, GA: TAPPI Press, 269-288. 
SYNTHETIC VITREOUS FIBERS 239 

9. REFERENCES 

*Hesterberg TW, Hart GA. 2000. Lung biopersistence and in vitro dissolution rate predict the 

pathogenic potential of synthetic vitreous fibers. Inhal Toxicol 12:91-97. 

*Hesterberg TW, Hart GA. 2001. Synthetic vitreous fibers: A review of toxicology research and its 

impact on hazard classification. Crit Rev Toxicol 31(1):1-53. 

Hesterberg TW, Axten C, McConnell EE, et al. 1997. Chronic inhalation study of fiber glass and 

amosite asbestos in hamsters: Twelve-month preliminary results. Environ Health Perspect Suppl 

105(5):1223-1229. 

*Hesterberg TW, Axten C, McConnell EE, et al. 1999. Studies on the inhalation toxicology of two 

fiberglasses and amosite asbestos in the Syrian golden hamster. Part I. Results of a subchronic study and 

dose selection for a chronic study. Inhal Toxicol 11(9):747-784. 

Hesterberg TW, Butterick CJ, Oshimura M. 1986. Role of phagocytosis in Syrian hamster cell 

transformation and cytogenetic effects induced by asbestos and short and long glass fibers. Cancer Res 

46(11):5795-5802. 

*Hesterberg TW, Chase G, Axten C, et al. 1998a. Biopersistence of synthetic vitreous fibers and amosite 

asbestos in the rat lung following inhalation. Toxicol Appl Pharmacol 151:262-275. 

*Hesterberg TW, Chase G, Axten C, et al. 1999. Erratum: Biopersistence of synthetic vitreous fibers 

and amosite asbestos in the rat lung following inhalation. Toxicol Appl Pharmacol 155:292. 

*Hesterberg TW, Hart GA, Bunn WB. 1993a. In vitro toxicology of fibers: mechanistic studies and 

possible use for screening assays. In: Warheit DB, ed. Fiber toxicology. Chapter 7. San Diego, CA: 

Academic Press, Inc., 139-170. 

*Hesterberg TW, Hart GA, Chevalier J, et al. 1998b. The importance of fiber biopersistence and lung 

dose in determining the chronic inhalation effects of X607, RCF1, and chrysotile asbestos in rats. 

Toxicol Appl Pharmacol 153:68-82. 

Hesterberg TW, Hart GA, Miiller WC, et al. 2002. Use of short-term assays to evaluate the potential 

toxicity of two new biosoluble glasswool fibers. Inhal Toxicol 14:217-246. 

Hesterberg TW, Miiller WC, Anderson R. 1993b. Chronic inhalation studies of man-made vitreous 

fibers. Proceedings of the 22nd DOE/NRC Nuclear Air Cleaning Conference 1992. Vol 1:191-204. 

Hesterberg TW, Miiller WC, Mast R, et al. 1994. Relationship between lung biopersistence and 

biological effects of man-made vitreous fibers after chronic inhalation in rats. Environ Health Perspect 

102:133-137. 

*Hesterberg TW, Miiller WC, McConnell EE, et al. 1993c. Chronic inhalation toxicity of size-separated 

glass fibers in Fischer 344 rats. Fundam Appl Toxicol 20:464-476. 

*Hesterberg TW, Miiller WC, McConnell EE, et al. 1994. Chronic inhalation toxicity of man-made 

vitreous fibers: Relationship to lung burden and lung retention. In: Dungworth DL, Mauderly JL, 

Oberdorster G, eds. Toxic and carcinogenic effects of solid particles in the respiratory tract. Washington, 

DC: ILSI Press., 455-459. 
 

SYNTHETIC VITREOUS FIBERS 240 

9. REFERENCES 

*Hesterberg TW, Miiller WC, Musselman RP, et al. 1996. Biopersistence of man-made vitreous fibers 

and crocidolite asbestos in the rat lung following inhalation. Fundam Appl Toxicol 29:267-279. 

*Hesterberg TW, Oshimura M, Barrett JC. 1985. In: Beck EG, Bignon J, eds. In vitro effects of 

mineral dusts. Third International Workshop. Berlin: Springer-Verlag, 185-196. 

Hill IM, Beswick PH, Donaldson K. 1996. Enhancement of the macrophage oxidative burst by 

immunoglobulin coating of respirable fibers: Fiber-specific differences between asbestos and man-made 

fibers. Exp Lung Res 22(2):133-148. 

*Hill JW, Whitehead WS, Cameron JD, et al. 1973. Glass fibres: absence of pulmonary hazard in 

production workers. Br J Ind Med 30:174-179. 

Hinnen U, Elsner P, Barraud M, et al. 1997. Foreign body granuloma of the penis caused by 

occupational glass fibre exposure. Genitourin Med 73:577-578. 

Hippeli S, Dornisch K, Kaiser S, et al. 1997. Biological durability and oxidative potential of a stonewool 

mineral fibre compared to crocidolite asbestos fibers. Arch Toxicol 71(8):532-535. 

*Hirvonen A. 1997. Combinations of susceptible genotypes and individual responses to toxicants. 

Environ Health Perspect 105(suppl 4):755-757. 

Hirvonen A, Mattson K, Karjaiainen T, et al. 1999. Simian virus 40 (SV40)-like DNA sequences not 

detectable in Finnish mesothelioma patients not exposed to SV40-contaminated polio vaccines. Mol 

Carcinog 26:93-99. 

*Hirvonen A, Saarikoski ST, Linnainmaa K, et al. 1996. Gluthione S-transferase and N-acetyltransferase 

genotypes and asbestos-associated pulmonary disorders. J Natl Cancer Inst 88(24):1853-1856. 

Hoch-Ligetti C, Sass B, Sobel HJ, et al. 1983. Endocardial tumors in rats exposed to durable fibrous 

materials. J Natl Cancer Inst 71(5):1067-1071. 

*Hoel DG, Davis DL, Miller AB, et al. 1992. Trends in cancer mortality in 15 industrialized countries, 

1969-1986. J Natl Cancer Inst 84(5):313-320. 

*Hohr D. 1985. [Investigations by transmission electron microscopy of fibrous particles in ambient air.] 

Staub Reinhalt Luft 45:171-174. (German) 

Holmes A, Morgan A, Davison W. 1983. Formation of pseudo-asbestos bodies on sized glass fibres in 

the hamster lung. Ann Occup Hyg 27(3):301-313. 

Hori H, Ishimatsu S, Oyabu T, et al. 1999. A clearance model of inhaled man-made fibers in rat lungs. 

Ind Health 37(1):103-107. 

Horowitz LD. 1978. NIOSH Criteria Document on fibrous glass. J Occup Med 20(11):718, 720. 

*Horvath HP. 1995. Health effects of man-made mineral fibers. Cleve Clin J Med 62(1):8-19. 

Hoskins JA, Brown RC. 1994. Contamination of the air with mineral fibers following the explosive 

destruction of buildings and fire. Drug Metab Rev 26(4):663-673. 
 

SYNTHETIC VITREOUS FIBERS 241 

9. REFERENCES 

Howden PJ, Faux SP. 1996a. Fibre-induced lipid peroxidation leads to DNA adduct formation in 

Salmonella typhimurium TA104 and rat lung fibroblasts. Carcinogenesis 17(3):413-419. 

Howden PJ, Faux SP. 1996b. Glutathione modulates the formation of 8-hydroxdeoxyguanosine in 

isolated DNA and mutagenicity in Salmonella typhimurium TA 100 induced by mineral fibres. 

Carcinogenesis 17(10):2275-2277. 

Huang JQ, Ji CM. 1994. A survey of the health effect of continuous filament glass fibre on long-term 

exposed workers. Ann Occup Hyg 38:763-768. 

Huff J. 2002. IARC monographs, industrial influence, and upgrading, downgrading, and under-grading 

chemicals. Int J Occup Environ Health 8:249-270. 

*Hughes JM, Jones RN, Glindmeyer HW, et al. 1993. Follow up study of workers exposed to man made 

mineral fibres. Br J Ind Med 50:658-667. 

*Hunting KL, Welch LS. 1993. Occupational exposure to dust and lung disease among sheet metal 

workers. Br J Ind Med 50(5):432-442. 

IARC. 1987. Asbestos. IARC monographs programme on the evaluation of carcinogenic risks to 

humans. International Agency for Research on Cancer. 

http://193.51.164.11/htdocs/Monographs/Suppl7/Asbestos.html. May 07, 2002. 

*IARC. 1988. IARC monographs of the evaluation of carcinogenic risks to human. International 

Agency for Research on Cancer. Lyon, France: World Health Organization. IARC Sci Publ 43:39-171. 

*IARC. 2001. Man-made mineral fibres. IARC monographs programme on the evaluation of 

carcinogenic risks to humans. International Agency for Research on Cancer. 

http://193.51.164.11/htdocs/Monographs/Vol43/43-01.htm. May 07, 2002. 

*IARC. 2002. Man-made mineral fibres. IARC monographs programme on the evaluation of 

carcinogenic risks to humans. International Agency for Research on Cancer. 

http://193.51.164.11/htdocs/monographs/vol81/81.html. Feburary 02, 2004. 

*IARC Expert Panel. 1996. Congress report. In: Kane AB, Boffetta P, Saracci R, et al., eds. 

Mechanisms of fibre carcinogenesis. International Agency for Research on Cancer. Scientific 

Publications No. 140, 1-9. 

Infante PF, Schuman LD, Dement J, et al. 1994a. Fibrous glass and cancer. Am J Ind Med 26:559-584. 

Infante PF, Schuman LD, Dement J, et al. 1994b. Fibrous glass and cancer: Commentary. Am J Ind 

Med 26:559-584. 

Infante PF, Schuman LD, Huff J. 1996. Fibrous glass insulation and cancer: Response and rebuttal. Am 

J Ind Med 30:113-120. 

*ILO. 1989. International Labour Office. Guidelines for the use of the ILO international classification 

of radiographs of pneumoconiosis, revised edition. Geneva, Switzerland: ILO Occupational Safety and 

Health Series. No. 22. 
SYNTHETIC VITREOUS FIBERS 242 

9. REFERENCES 

ILSI. 2000. The relevance of the rat lung response to particle overload for human risk assessment: A 

workshop concensus report. ILSI Risk Science Institute Workshop. International Life Sciences Institute. 

Inhal Toxicol 12:1-17. 

*IRIS. 2004. Integrated Risk Information System. http://www.epa.gov/iris. January 08, 2004. 

Ishihara Y. 2001. In vitro studies on biological effects of fibrous minerals. Ind Health 39:94-105. 

Ishimatsu S, Oyabu T, Hori H, et al. 1999. A new digestion method for recovery of MMMFs from lungs. 

Ind Health 37(3):307-312. 

Iwata T, Yano E. 2003. Reactive oxygen metabolite production induced by asbestos and glass fibers: 

Effect of fiber milling. Ind Health 41:32-38. 

*Jacob TR, Hadley JG, Bender JR, et al. 1992. Airborne glass fiber concentrations during installation of 

residential insulation. Am Ind Hyg Assoc J 53(8):519-523. 

*Jacob TR, Hadley JG, Bender JR, et al. 1993. Airborne glass fiber concentrations during manufacturing 

operations involving glass wool insulation. Am Ind Hyg Assoc J 54(6):320-326. 

Jacobsen M. 1983. Do we know enough from epidemiology to prevent asbestosis? Eur J Respir Dis 

64:407-408. 

*Jaffrey TSAM. 1990. Levels of airborne man-made mineral fibres in UK dwellings. I. Fibre levels 

during and after installation of insulation. Atmos Environ 24A(1):133-141. 

Janssen YMV, Borm PJA, Marsh JP, et al. 1994b. The role of active oxygen species in lung toxicity 

induced by mineral fibers and particulates. Adv Environ Sci Technol 28:445-457. 

*Janssen YMW, Heintz NH, Marsh JP, et al. 1994a. Induction of c-fos and c-jun proto-oncogenes in 

target cells of the lung and pleura by carcinogenic fibers. Am J Respir Cell Mol Biol 11:522-530. 

*Jarvholm B, Jarliden A-K, Lilja B-G, et al. 1995. Occurrence of pleural plaques in workers with 

exposure to mineral wool. Int Arch Occup Environ Health 67(5):343-346. 

Jaurand M-C. 1997. Mechanisms of fiber-induced genotoxicity. Environ Health Perspect Suppl 

105(5):1073-1084. 

Jaurand MC, Magne L, Bignon J, et al. 1980. Effects of well-defined fibres on red blood cells and 

alveolar macrophages. In: Wagner JC, Davis W, eds. Biological effects of mineral fibres. IARC 

Scientific Publication No. 30. Lyon, France. 

*Jeffress CN. 1999. Written communication (May 18, 1999) to Kenneth Mentzer, Executive Vice 

President, OSHA regarding expression of support for the “Health and Safety Partnership Program” to 

help protect employees involved in manufacturing, installing, and removing products containing synthetic 

vitreous fibers. 

*Jensen CG, Watson M. 1999. Inhibition of cytokinesis by asbestos and synthetic fibres. Cell Biol Int 

23(12):829-840. 
 

 

SYNTHETIC VITREOUS FIBERS 243 

9. REFERENCES 

*Johanson CE. 1980. Permeability and vascularity of the developing brain: Cerebellum vs cerebral 

cortex. Brain Res 190:3-16. 

Johnson NF. 1993. The limitations of inhalation, intratracheal, and intracoelomic routes of 

administration for identifying hazardous fibrous materials. In: Warheit DB, ed. Fiber toxicology. 

Chapter 3. San Diego, CA: Academic Press, Inc., 43-72. 

Johnson NF. 1994. An overview of animal models for assessing synthetic vitreous fibers (SVFs) safety. 

Regul Toxicol Pharmacol 20:S7-S21. 

Johnson NF. 1994. Phasgosomal pH and glass fiber dissolution in cultured nasal epithelial cells and 

alveolar macrophages: A preliminary study. Environ Health Perspect 102:97-102. 

Johnson NF, Hahn FF. 1996. Induction of mesothelioma after intrapleural inoculation of F344 rats with 

silicon carbide whiskers or continuous ceramic filaments. Occup Environ Med 53(12):813-816. 

*Johnson NF, Jaramillo RJ. 1997. p53, Cip 1, and Gadd 153 expression following treatment of A549 

cells with natural and man-made vitreous fibers. Environ Health Perspect 105:1143-1145. 

*Johnson NF, Wagner JC. 1980. A study by electron microscopy of the effects of chrysotile and manmade mineral fibres on rat lungs. In: Wagner JC, Davis W, eds. Biological effects of mineral fibers. 

IARC Sci Publ 30:293-303. 

*Johnson DL, Healey JJ, Ayer EA, et al. 1969. Exposure to fibers in the manufacture of fibrous glass. 

Am Ind Hyg Assoc J 30:545-550. 

Johnson NF, Hoover MD, Thomassen DG, et al. 1992. In vitro activity of silicon carbide whiskers in 

comparison to other industrial fibers using four cell culture systems. Am J Ind Med 21(6):807-823. 

Jolanki R, Makinen I, Suuronen K, et al. 2002. Occupational irritant contact dermatitis from synthetic 

mineral fibres according to Finnish statistics. Contact Dermatitis 47:329-333. 

*Jones AD. 1993. Respirable industrial fibres: Deposition, clearance and dissolution in animal models. 

Ann Occup Hyg 37(2):211-226. 

Julier F, Tiesler H, Zindler G. 1993. [Measurement of fibrous dust concentrations when handling 

mineral-wool insulations on industrial building sites.] Staub Reinhalt Luft 53(6):245-250. (German) 

*Kamstrup O, Davis JMG, Ellehauge A, et al. 1998. The biopersistence and pathogenicity of man-made 

vitreous fibres after short- and long-term inhalation. Ann Occup Hyg 42(3):191-199. 

*Kamstrup O, Ellehauge A, Chevalier J, et al. 2001. Chronic inhalation studies of two types of stone 

wool fibers in rats. Inhal Toxicol 13(7):603-621. 

Kamstrup O, Ellehauge A, Collier CG, et al. 2002. Carcinogenicity studies after intraperitoneal injection 

of two types of stone wool fibres in rats. Ann Occup Hyg 46:135-142. 

*Kane AB. 1996. Mechanisms of mineral fibre carcinogenesis. In: Kane AB, Bofetta P, Saracci R, et 

al., eds. Mechanisms of fibre carcinogenesis. International Agency for Research on Cancer, 11-34. 
SYNTHETIC VITREOUS FIBERS 244 

9. REFERENCES 

Keegan TE, Simmons JE, Pegram RA. 1998. NOAEL and LOAEL determinations of acute 

hepatotoxicity for chloroform and bromodichloromethane delivered in an aqueous vehicle to F344 rats. J 

Toxicol Environ Health A 55(1):65-75. 

Kelly JT, Kimbell JS, Asgharian B. 2001. Particle deposition in a rat nasal mold. CIIT Activities. 

Research Triangle Park, NC: CIIT Centers for Health Professionals, 1-6. 

*Kelsey KT, Nelson HN, Wiencke JK, et al. 1997. The glutathione S-transferase Θ and μ deletion 

polymorphisms in asbestosis. Am J Ind Med 31:274-279. 

*Kiec-Swierczynska M, Szymczk W. 1995. The effect of the working environment on occupational skin 

disease development in workers processing rockwool. Int J Occup Med Environ Health 8(1):17-22. 

*Kiec-Swierczynska M, Wojtczak J. 2000. Occupational ceramic fibres dermatitis in Poland. Occup 

Med 50(5):337-342. 

Kilburn KH. 1993. Pulmonary effects of exposure to fine fiberglass: irregular opacities and small 

airways obstruction. Reply to comments. Br J Ind Med 50(4):383-384. 

*Kilburn KH, Warshaw RH. 1992. Difficulties of attribution of effect in workers exposed to fiberglass 

and asbestos. Am Ind Hyg Assoc J 20(6):745-751. 

*Kilburn KH, Powers D, Warshaw RH. 1992. Pulmonary effects of exposure to fine fiberglass: 

irregular opacities and small airways obstruction. Br J Ind Med 49:714-720. 

Kim J-H, Chang H-S, Kim K-Y, et al. 1999. Environmental measurements of total dust and fiber 

concentration in manufacturer and user of man-made mineral fibers. Ind Health 37(3):322-328. 

Kim K-A, Lee WK, Kim JK, et al. 2001. Mechanism of refractory ceramic fiber- and rock wool-induced 

cytotoxicity in alveolar macrophages. Int Arch Occup Environ Health 74(1):9-15. 

*Kjaerheim K, Boffetta P, Hansen J, et al. 2002. Lung cancer among rock and slag wool production 

workers. Epidemiology 13:445-453. 

Klingholz R. 1977. Technology and production of man-made mineral fibres. Ann Occup Hyg 20:153­

159. 

*Knudsen T, Guldberg M, Christensen VR, et al. 1996. New type of stone wool (HT fibres) with a high 

dissolution rate at pH=4.5. Glastech Ber 69(10):331-337. 

Koenig AR, Axten CW. 1995. Exposures to airborne fiber and free crystalline silica during installation 

of commercial and industrial mineral wool products. Am Ind Hyg Assoc J 56(10):1016-1022. 

*Koh D, Khoo NY. 1995. Environmental glass fibre counts and skin symptoms. Contact Dermatitis 

32(3):185. 

*Koh D, Aw TC, Foulds IS. 1992. Fiberglass dermatitis from printed circuit boards. Am J Ind Med 

21:193-198. 
 

SYNTHETIC VITREOUS FIBERS 245 

9. REFERENCES 

*Komori M, Nishio K, Kitada M, et al. 1990. Fetus-specific expression of a form of cytochrome P-450 

in human livers. Biochemistry 29:4430-4433. 

Konzen J. 1975. Observations on fibrous glass in relation to health. In: Zenz C, ed. Occupational 

medicine. Principles and practical applications. Chapter 13. Chicago, IL: YearBook Medical 

Publishers, Inc., 231-238. 

Konzen JL. 1980. Man-made vitreous fibers and health. Proceedings National Workshop on Substitutes 

for Asbestos. EPA560380001. 

Konzen JL. 1994. Comment on: Occupational exposure to dust and lung disease among sheet metal 

workers. Br J Ind Med 50(5):432-442. 

*Koshi K, Kohyama N, Myojo T, et al. 1991. Cell toxicity hemolytic action and clastogenic activity of 

asbestos and its substitutes. Ind Health 29(2):37-56. 

Krantz S. 1988. Exposure to man-made mineral fibers at ten production plants in Sweden. Scand J 

Work Environ Health 14:49-51. 

*Krishnan K, Andersen ME. 1994. Physiologically based pharmacokinetic modeling in toxicology. In: 

Hayes AW, ed. Principles and methods of toxicology. 3rd ed. New York, NY: Raven Press, Ltd., 149­

188. 

*Krishnan K, Andersen ME, Clewell HJ III, et al. 1994. Physiologically based pharmacokinetic 

modeling of chemical mixtures. In: Yang RSH, ed. Toxicology of chemical mixtures: Case studies, 

mechanisms, and novel approaches. San Diego, CA: Academic Press, 399-437. 

Kudo Y, Watanabe M, Okada M, et al. 2003. Comparative cytotoxicity study of rock wool and 

chrysotile by cell magnetometric evaluation. Inhal Toxicol 15:1275-1295. 

Lafuma J, Morin M, Poncy JL, et al. 1980. Mesothelioma induced by intrapleural injection of different 

types of fibres in rats; synergistic effect of other carcinogens. In: Wagner JC, Davis W, eds. Biological 

effects of mineral fibres. IARC Sci Publ 30:311-320. 

Lambre C, Schorsch F, Blanchard O, et al. 1998. An evaluation of the carcinogenic potential of five 

man-made vitreous fibers using the intraperitoneal test. Inhal Toxicol 10(11):995-1021. 

Law BD, Bunn WB, Hesterberg TW. 1990. Solubility of polymeric organic fibers and manmade 

vitreous fibers in gambles solution. Inhal Toxicol 2(4):321-339. 

Law BD, Bunn WB, Hesterberg TW. 1991. Dissolution of natural mineral and man-made vitreous fibers 

in Karnovsky's and formalin fixatives. Inhal Toxicol 3(3):309-321. 

*Lea CS, Hertz-Picciotto I, Andersen A, et al. 1999. Gender differences in the healthy worker effect 

among synthetic vitreous fiber workers. Am J Epidemiol 150(10):1099-1106. 

Leadbetter MR, Corn M. 1972. Particle size distribution of rat lung residues after exposure to fiberglass 

dust clouds. Am Ind Hyg Assoc J 33(8):511-522. 
SYNTHETIC VITREOUS FIBERS 246 

9. REFERENCES 

*Leanderson P, Tagesson C. 1989. Cigarette smoke potentiates the DNA-damaging effect of manmade 

mineral fibers. Am J Ind Med 16(6):697-706. 

*Leanderson P, Soderkvist P, Tagesson C, et al. 1988. Formation of 8-hydroxydeoxyguanosine by 

asbestos and man made mineral fibres. Br J Ind Med 45:309-311. 

*Leanderson P, Soderkvist P, Tagesson C. 1989. Hydroxyl radical mediated DNA base modification by 

manmade mineral fibres. Br J Ind Med 46:435-438. 

*LeBouffant L, Daniel H, Henin JP, et al. 1987. Experimental study on long-term effects of inhaled 

MMMF on the lungs of rats. Ann Occup Hyg 31(48):765-790. 

*Lee J-M, Hennekens CH, Trichopoulos D, et al. 1995. Man-made vitreous fibers and risk of respiratory 

system cancer: A review of the epidemiologic evidence. J Occup Environ Med 37(6):725-738. 

Lee KP, Barras CE, Griffith FD. 1979. Pulmonary response to glass fiber by inhalation exposure. Lab 

Invest 40(2):123-133. 

*Lee KP, Barras CE, Griffith FD, et al. 1981b. Comparative pulmonary responses to inhaled inorganic 

fibers with asbestos and fiberglass. Environ Res 24:167-191. 

*Lee KP, Barras CE, Griffith FD, et al. 1981a. Pulmonary response and transmigration of inorganic 

fibers by inhalation exposure. Am J Pathol 102(3):314-323. 

*Lee WJ, Baris D, Jarvholm B, et al. 2003. Multiple myeloma and diesel and other occupational 

exposures in Swedish construction workers. Int J Cancer 107:134-138. 

*Leeder JS, Kearns GL. 1997. Pharmacogenetics in pediatrics: Implications for practice. Pediatr Clin 

North Am 44(1):55-77. 

Lees PSJ, Breysse PN, McArthur BR, et al. 1993. End user exposures to man-made vitreous fibers: I. 

Installation of residential insulation products. Appl Occup Environ Hyg 8(12):1022-1030. 

*Leikauf GD, Fink SP, Miller M, et al. 1995. Refractory ceramic fibers activate alveolar macrophage 

eicosanoid and cytokine release. J Appl Physiol 78(1):164-171. 

Lemaire I, Dionne PG, Nadeau D, et al. 1989. Rat lung reactivity to natural and man-made fibrous 

silicates following short-term exposure. Environ Res 48:193-210. 

*Lemasters G, Lockey J, Levin L, et al. 1998. An industry-wide pulmonary study of men and women 

manufacturing refractory ceramic fibers. Am J Epidemiol 148(9):910-919. 

Lemasters G, Lockey J, Levin L, et al. 2001. A longitudinal study of chest radiographic changes and 

mortality of workers in the refractory ceramic fiber industry. Am J Epidemiol 153(11):S264. 

*Lemasters G, Lockey J, Rice C, et al. 1994. Radiographic changes among workers manufacturing 

refractory ceramic fibre and products. Ann Occup Hyg 38:745-751. 

*Lemasters G, Lockey J, Yiin JH, et al. 2003. Mortality of workers occupationally exposed to refractory 

ceramic fibers. J Occup Environ Med 45:440-450. 
SYNTHETIC VITREOUS FIBERS 247 

9. REFERENCES 

Lemen RA. 2001. Fiberglass. In: Bingham E, Cohrssen B, Powell CH, eds. Patty's toxicology. John 

Wiley & Sons, 575-582. 

Lentz TJ, Rice CH, Lockey JE. 1999. Potential significance of airborne fiber dimensions measured in 

the US refractory ceramic fiber manufacturing industry. Am J Ind Med 36(2):286-298. 

*Lentz TJ, Rice CH, Succop PA, et al. 2003. Pulmonary deposition modeling with airborne fiber 

exposure data: A study of workers manufacturing refractory ceramic fibers. Appl Occup Environ Hyg 

18:278-288. 

*Leung H-W. 1993. Physiologically-based pharmacokinetic modeling. In: Ballentine B, Marro T, 

Turner P, eds. General and applied toxicology. Vol. 1. New York, NY: Stockton Press, 153-164. 

Lindgren F, Sjosstrom M, Berglind R, et al. 1996. Modeling of the biological activity for a set of 

ceramic fibre materials: A QSAR study. SAR QSAR Environ Res 5:299-310. 

*Lippmann M. 1990. Effects of fiber characteristics on lung deposition, retention, and disease. Environ 

Health Perspect 88:311-317. 

*Lippmann M. 1994. Deposition and retention of inhaled fibres: effects on incidence of lung cancer and 

mesothelioma. Occup Environ Med 51:793-798. 

*Livingston, AL. 1978. Forage plant estrogens. J Toxicol Environ Health 4:301-324. 

Lockey JE. 1996. Man-made fibers and nonasbestos fibrous silicates. In: Harber P, Scheneker MB, 

Balmes JR, eds. Occupational and respiratory disease. Chapter 21. Mosby-Year Book, Inc., 330-344. 

*Lockey JE, Lemasters GK, Levin L, et al. 2002. A longitudinal study of chest radiographic changes of 

workers in the refractory ceramic fiber industry. Chest 121:2044-2051. 

*Lockey J, Lemasters G, Rice C, et al. 1996. Refractory ceramic fiber exposure and pleural plaques. 

Am J Respir Crit Care Med 154(5):1405-1410. 

*Lockey JE, Levin LS, Lemasters GK, et al. 1998. Longitudinal estimates of pulmonary function in 

refractory ceramic fiber manufacturing workers. Am J Respir Crit Care Med 157(4 Pt 1):1226-1233. 

*Longley EO, Jones RC. 1966. Fiberglass conjunctivitis and keratitis. Arch Environ Health 13:790-793. 

Luce D, Leclerc A, Begin D, et al. 2002. Sinonasal cancer and occupational exposures: A polled 

analysis of 12 case-control studies. Cancer Causes Control 13:147-157. 

Luoto K, Holopainen M, Perander M, et al. 1996. Cellular effects of particles-impact of dissolution on 

toxicity of man-made mineral fibers. Cent Eur J Public Health 4:29-32. 

*Luoto K, Holopainen M, Sarataho M, et al. 1997. Comparison of cytotoxicity of man-made vitreous 

fibres. Ann Occup Hyg 41(1):37-50. 
 

 

SYNTHETIC VITREOUS FIBERS 248 

9. REFERENCES 

Luoto K, Holopainen M, Savolainen K. 1994. Scanning electron microscopic study on the changes in the 

cell surface morphology of rat alveolar macrophages after their exposure to man-made vitreous fibers. 

Environ Res 66:198-207. 

Luoto K, Holopainen M, Savolainen K. 1995. Durability of man-made vitreous fibres as assessed by 

dissolution of silicon, iron and aluminium in rat alveolar macrophages. Ann Occup Hyg 39(6):855-867. 

Ma Z, Otsuki T, Tomokuni A, et al. 1999. Man-made mineral fibers induce apotosis of human peripheral 

blood mononuclear cells similarly to chrysotile B. Int J Mol Med 4(6):633-637. 

Maltoni C, Minardi F, Soffritti M, et al. 1991. Long-term carcinogenicity bioassays on industrial 

chemicals, and man-made mineral fibers, at the Bentivoglio (BT) Laboratories of the Bologna Institute of 

Oncology: Premises, programs, and results. Toxicol Ind Health 7(516):63-94. 

*Marchand JL, Luce D, Lecierc A, et al. 2000. Laryngeal and hypopharyngeal cancer and occupational 

exposure to asbestos and man-made vitreous fibers: Results of a case-control study. Am J Ind Med 

37(6):581-589. 

*Marchant GE, Amen MA, Bullock CH, et al. 2002. A synthetic vitreous fiber (SVF) occupational 

exposure database: Implementing the SVF health and safety partnership program. Appl Occup Environ 

Hyg 17:276-285. 

Marconi A, Corradetti E, Mannozzi A. 1987. Concentrations of man-made vitreous fibres during 

installation of insulation materials aboard ships at Ancona naval dockyards. Ann Occup Hyg 31(4B):595­

599. 

*Marks-Konczalik J, Gillissen A, Jaworska M, et al. 1998. Induction of manganese superoxide 

dismutase gene expression in bronchoepithelial cells after rockwool exposure. Lung 176(3):165-180. 

*Marsh GM, Buchanich JM, Youk AO. 2001a. Historical cohort study of US man-made vitreous fiber 

production workers. VI. Respiratory system cancer standardized mortality ratios adjusted for the 

confounding effect of cigarette smoking. J Occup Environ Med 43(9):803-808. 

*Marsh GM, Enterline PE, Stone RA, et al. 1990. Mortality among a cohort of U.S. man-made mineral 

fiber workers: 1985 follow-up. J Occup Environ Med 32:594-604. 

*Marsh GM, Gula MJ, Youk AO, et al. 2001b. Historical cohort study of U.S. man-made vitreous fiber 

production workers: II. Mortality from mesothelioma. J Occup Environ Med 43(9):757-766. 

Marsh GM, Stone RA, Youk AO, et al. 1997. Cancer mortality among man-made vitreous fiber 

production workers. Letter to the editor. Epidemiology 9(2):218-220. 

*Marsh GM, Youk AO, Stone RA, et al. 2001c. Historical cohort study of US man-made vitreous fiber 

production workers: I. 1992 fiberglass cohort follow-up: Initial findings. J Occup Environ Med 

43(9):741-756. 

Mast RW, Hesterberg TW, Glass LR, et al. 1994. Chronic inhalation and biopersistence of refractory 

ceramic fiber in rats and hamsters. Environ Health Perspect Suppl 102(5):207-209. 
SYNTHETIC VITREOUS FIBERS 249 

9. REFERENCES 

*Mast RW, Maxim LD, Utell MJ, et al. 2000. Refractory ceramic fiber: Toxicology, epidemiology, and 

risk analyses- A review. Inhal Toxicol 12(5):359-399. 

*Mast RW, McConnell EE, Hesterberg TW, et al. 1995b. Multiple-dose chronic inhalation toxicity 

study of size-separated kaolin refractory ceramic fiber in male Fischer 344 rats. Inhal Toxicol 7(4):469­

502. 

*Mast RW, McConnell EE, Anderson R, et al. 1995a. Studies on the chronic toxicity (inhalation) of four 

types of refractory ceramic fiber in male Fischer 344 rats. Inhal Toxicol 7:425-467. 

*Mattson SM. 1994. Glass fiber dissolution in simulated lung fluid and measures needed to improve 

consistency and correspondence to in vivo dissolution. Environ Health Perspect 102:87-90. 

*Maxim LD, McConnell EE. 2001. Interspecies comparisons of the toxicity of asbestos and synthetic 

vitreous fibers: A weight-of-the-evidence approach. Regul Toxicol Pharmacol 33(3):319-342. 

*Maxim LD, Allshouse JN, Chen SH, et al. 2000a. Workplace monitoring of refractory ceramic fiber in 

the United States. Regul Toxicol Pharmacol 32(3):293-309. 

Maxim LD, Allshouse JN, Kelly WP, et al. 1997. A multiyear workplace-monitoring program for 

refractory ceramic fibers: Findings and conclusions. Regul Toxicol Pharmacol 26(2):156-171. 

Maxim LD, Allshouse JN, Venturin DE. 2000b. The random-effects model applied to refractory ceramic 

fiber data. Regul Toxicol Pharmacol 32(2):190-199. 

Maxim LD, Boymel P, Chase GR, et al. 2002. Indices of fiber biopersistence and carcinogen 

classification for synthetic vitreous fibers (SVFs). Regul Toxicol Pharmacol 35:357-378. 

*Maxim LD, Eastes W, Hadley JG, et al. 2003a. Fiber glass and rock/slag wool exposure of professional 

and do-it-yourself installers. Regul Toxicol Pharmacol 37:28-44. 

*Maxim LD, Kelly WP, Walters T, et al. 1994. A multiyear workplace-monitoring program for 

refractory ceramic fibers. Regul Toxicol Pharmacol 20:S200-S215. 

Maxim LD, Mast RW, Utell MJ, et al. 1999a. Hazard assessment and risk analysis of two new synthetic 

vitreous fibers. Regul Toxicol Pharmacol 30(1):54-74. 

*Maxim LD, Venturin D, Allshouse JN. 1999b. Respirable crystalline silica exposure associated with 

the installation and removal of RCF and conventional silica-containing refractories in industrial furnaces. 

Regul Toxicol Pharmacol 29(1):44-63. 

*Maxim LD, Yu CP, Oberdorster G, et al. 2003b. Quantitative risk analyses for RCF: Survey and 

synthesis. Regul Toxicol Pharmacol 38:400-416. 

*Mayr U, Butsch A, Schneider S. 1992. Validation of two in vitro test systems for estrogenic activities 

with zearalenone, phytoestrogens and cereal extracts. Toxicology 74:135-149. 

McClellan RO. 1994. Assessing health risks of synthetic vitreous fibers: An integrative approach. 

Regul Toxicol Pharmacol 20(9):S121-S134. 
 

SYNTHETIC VITREOUS FIBERS 250 

9. REFERENCES 

McClellan RO, Hesterberg TW. 1994. Role of biopersistence in the pathogenicity of man-made fibers 

and methods for evaluating biopersistence: A summary of two round-table discussions. Environ Health 

Perspect 102:277-283. 

McConnell EE. 1996. Commentary on "Fibrous glass and lung cancer". Letter to the editor. Am J Ind 

Med 30:109-110. 

McConnell EE. 2000. A science-based paradigm for the classification of synthetic vitreous fibers. Regul 

Toxicol Pharmacol 32(1):14-21. 

*McConnell EE, Axten C, Hesterberg TW, et al. 1999. Studies on the inhalation toxicology of two 

fiberglasses and amosite asbestos in the Syrian golden hamster. Part II. Results of chronic exposure. 

Inhal Toxicol 1(9):785-835. 

*McConnell EE, Kampstrup O, Musselman R, et al. 1994. Chronic inhalation study of size-separated 

rock and slag wool insulation fibers in Fischer 344/N rats. Inhal Toxicol 6:571-614. 

*McConnell EE, Mast RW, Hesterberg TW, et al. 1995. Chronic inhalation toxicity of a kaolin-based 

refractory ceramic fiber in Syrian golden hamsters. Inhal Toxicol 7:503-532. 

*McDonald AD, McDonald JC, Rando RJ, et al. 2001. Cohort mortality study of North American 

industrial sand workers. I. Mortality from lung cancer, silicosis and other causes. Ann Occup Hyg 

45(3):193-199. 

McDonald JC. 1998. Mineral fibre persistence and carcinogenicity. Ind Health 36:372-375. 

*McDonald JC, Armstrong BG, Edwards CW, et al. 2001. Case-referent survey of young adults with 

mesothelioma: I. Lung analyses. Ann Occup Hyg 45(7):513-518. 

*McDonald JC, Case BW, Enterline PE, et al. 1990. Lung dust analysis in the assessment of past 

exposure of man-made mineral fibre workers. Ann Occup Hyg 34:427-441. 

*Meeker GP, Brownfield IK, Clark RN, et al. 2001. The chemical composition and physical properties 

of amphibole from Libby, Montana: a progress report. Poster presentation, 2001. Asbestos Health 

Effects Conference. Sponsored by U.S. Environmental Protection Agency, May 24-25. San Francisco, 

CA. 

*Melton CW, Anderson SJ, Dye CF, et al. 1978. Development of a rapid analytical method for 

determining asbestos in water. Gov Rep Announce Index (U.S.) 1979, 79(11), 80. 

*Mentzer, KD. 1999. Written communication (May 18, 1999) to Dr. Adam Finkel, Director of Health 

Standards, OSHA regarding voluntary health and safety partnership program for fiber glass, rock and slag 

wool fiber products. 

Miettinen OS, Rossiter CE. 1990. Man-made mineral fibers and lung cancer. Scand J Work Environ 

Health 16(4):221-231. 

*Milby TH, Wolf CR. 1969. Respiratory tract irritation from fibrous glass inhalation. J Occup Med 

11(8):409-410. 
 

SYNTHETIC VITREOUS FIBERS 251 

9. REFERENCES 

Miller BG, Jones AD, Searl A, et al. 1999. Influence of characteristics of inhaled fibres on development 

of tumours in the rat lung. Ann Occup Hyg 43(3):167-179. 

Miller BG, Searl A, Davis JMG, et al. 1999. Influence of fibre length, dissolution and biopersistence on 

the production of mesothelioma in the rat peritoneal cavity. Ann Occup Hyg 43(3):155-166. 

Miller K, Hudspith BN, Meredith C. 1994. The effect of MMMF on the kinetics of cytokine expression 

in murine lung populations: Role in fibre-induced disease. NATO ASI Ser H 85:79-90. 

*Miller ME, Lees PSJ, Breysse PN. 1995. A comparison of airborne man-made vitreous fiber 

concentrations before and after installation of insulation in a new construction housing. Appl Occup 

Environ Hyg 10(3):182-187. 

Milton DK, Walters MD, Hammond K, et al. 1996a. Worker exposure to endotoxin, phenolic 

compounds, and formaldehyde in a fiberglass insulation manufacturing plant. Am Ind Hyg Assoc J 

57:889-896. 

Milton DK, Wypij D, Kriebel D, et al. 1996b. Endotoxin exposure-response in a fiberglass 

manufacturing facility. Am J Ind Med 29:3-13. 

*Minamoto K, Nagano M, Inaoka T, et al. 2002. Skin problems among fiber-glass reinforced plastics 

factory workers in Japan. Ind Health 40:42-50. 

Mirer FE, Park RM. 1993. A case-control study of malignant and non-malignant disease among 

employees of a fiberglass manufacturing facility. Comments. Br J Ind Med 50(3):287. 

Mitchell RI, Donofrio DJ, Moorman WJ. 1986. Chronic inhalation toxicity of fibrous glass in rats and 

monkeys. J Am Coll Toxicol 5(6):545-575. 

Miyamoto K, Hiramatsu K, Ohtaki Y, et al. 1995. Effects of gomisin A on the promotor action and 

serum bile acid concentration in hepatocarcinogenesis induced by 3'-methyl-4-dimethylaminoazobenzene. Biol Pharm Bull 18(10):1443-1445. 

*Mohr U, Pott F, Vonnahme FJ. 1984. Morphological aspects of mesotheliomas after intratracheal 

instillations of fibrous dusts in Syrian golden hamsters. Exp Pathol 26(3):179-183. 

Monchaux G, Bignon J, Hirsch A, et al. 1982. Translocation of mineral fibres through the respiratory 

system after injection into the pleural cavity of rats. Ann Occup Hyg 26(1-4):309-318. 

*Monchaux G, Bignon J, Jaurand MC, et al. 1981. Mesotheliomas in rats following inoculation with 

acid-leached chrysotile asbestos and other mineral fibers. Carcinogenesis 2(3):229-236. 

Moolgavkar SH, Brown RC, Turim J. 2001a. Biopersistence, fiber length, and cancer risk assessment for 

inhaled fibers. Inhal Toxicol 13(9):755-772. 

Moolgavkar SH, Luebeck EG, Turim J, et al. 2000. Lung cancer risk associated with exposure to manmade fibers. Drug Chem Toxicol 23(1):223-242. 

Moolgavkar SH, Turim J, Brown RC, et al. 2001b. Long man-made fibers and lung cancer risk. Regul 

Toxicol Pharmacol 33:138-146. 
SYNTHETIC VITREOUS FIBERS 252 

9. REFERENCES 

Moore MA, Boymel PM, Maxim LD. 2002. Categorization and nomenclature of vitreous silicate wools. 

Regul Toxicol Pharmacol 35(1):1-13. 

*Morgan RW. 1981. Mortality study of fibrous glass production workers. Arch Environ Health 36:179­

183. 

Morgan A. 1994. In vivo evaluation of chemical biopersistence of man-made mineral fibers. Environ 

Health Perspect 102:127-131. 

*Morgan A. 1995. Deposition of inhaled asbestos and man-made mineral fibers in the respiratory tract. 

Ann Occup Hyg 39(5):747-758. 

*Morgan A, Holmes A. 1980. Concentrations and dimensions of coated and uncoated asbestos fibres in 

the human lung. Br J Ind Med 37:25-32. 

Morgan A, Holmes A. 1984. Solubility of rockwool fibres in vivo and the formation of pseudo-asbestos 

bodies. Ann Occup Hyg 28(3):307-314. 

Morgan A, Holmes A. 1986. Solubility of asbestos and man-made mineral fibers in vitro and in vivo: Its 

significance in lung disease. Environ Res 39:475-484. 

*Morgan A, Black A, Evans N, et al. 1980. Deposition of sized glass fibres in the respiratory tract of the 

rat. Ann Occup Hyg 23:353-366. 

*Morgan A, Collier CG, Morris KJ, et al. 1993. A radioactive tracer technique to determine in vivo the 

number of fibers in the lungs of rats following their administration by intratracheal instillation. Environ 

Res 182-190. 

Morgan A, Davis JA, Mattson SM, et al. 1994b. Effect of chemical composition on the solubility of 

glass fibres in vivo and in vitro. Ann Occup Hyg 38:609-617. 

*Morgan A, Holmes A, Davison W. 1982. Clearance of sized glass fibres from the rat lung and their 

solubility in vivo Ann Occup Hyg 25(3):317-331. 

*Morgan A, Morris KJ, Launder KA, et al. 1994a. Retention of glass fibers in the rat trachea following 

administration by intratracheal instillation. Inhal Toxicol 6:241-251. 

*Morgan A, Talbot RJ, Holmes A. 1978. Significance of fibre length in the clearance of asbestos fibres 

from the lung. Br J Ind Med 35:146-153. 

Morimoto Y, Tanaka I. 2001. In vivo studies of man-made mineral fibers- Fibrosis-related factors. Ind 

Health 39(2):106-113. 

*Morimoto Y, Kido M, Tanaka I, et al. 1993. Synergistic effects of mineral fibres and cigarette smoke 

on the production of tumour necrosis factor by alveolar macrophages of rats. Br J Ind Med 50(10):955­

960. 
 

SYNTHETIC VITREOUS FIBERS 253 

9. REFERENCES 

Morimoto Y, Tsuda T, Hirohashi M, et al. 1999. Effects of mineral fibers on the gene expression of 

proinflammatory cytokines and inducible nitric-oxide synthase in alveolar macrophages. Ind Health 

37(3):329-334. 

Morimoto Y, Tsuda T, Hori H, et al. 1999. Combined effect of cigarette smoke and mineral fibers on the 

gene expression of cytokine mRNA. Environ Health Perspect 107(6):495-500. 

Morimoto Y, Tsuda T, Nakamura H, et al. 1997. Expression of matrix metalloproteinases, tissue 

inhibitors of metalloproteinases, and extracellular matrix mRNA following exposure to mineral fibers and 

cigarette smoke in vivo. Environ Health Perspect Suppl 105(5):1247-1251. 

Morimoto Y, Tsuda T, Yamato H, et al. 2001. Comparison of gene expression of cytokines mRNA in 

lungs of rats induced by intratracheal instillation and inhalation of mineral fibers. Inhal Toxicol 

13(7):589-601. 

Morris GF, Brody AR. 1999. Stressing fibrogenesis in cell culture. Am J Respir Cell Mol Biol 

21(4):447-448. 

Morris KJ, Collier CG, Eastes W, et al. 1996. Comparison of biopersistence of experimental glass fibres 

in the lung and peritoneal cavity. Exp Toxicol Pathol 48(6):490-493. 

*Morris KJ, Launder KA, Morgan A, et al. 1995. Preliminary data from investigations of the in vivo 

biopersistence of three experimental glass fibres of varying chemical composition. Exp Toxicol Pathol 

47(2-3):179-182. 

*Morselli PL, Franco-Morselli R, Bossi L. 1980. Clinical pharmacokinetics in newborns and infants: 

Age-related differences and therapeutic implications. Clin Pharmacokin 5:485-527. 

Morton WE. 2002. Comment on historical cohort study of U.S. man-made vitreous fiber production 

workers. Letters to the editor. J Occup Environ Med 44(2):106-108. 

Mossman BT. 1988. Carcinogenic potential of asbestos and nonasbestos fibers. J Environ Sci Health 

Part C Environ Carcinogen Rev 6(2):151-195. 

*Mossman BT, Churg A. 1998. Mechanisms in the pathogenesis of asbestosis and silicosis. Am J 

Respir Crit Care Med 157:1666-1680. 

Moulin JJ, Mur JM, Wild P, et al. 1986. Oral cavity and laryngeal cancers among man-made mineral 

fiber production workers. Scand J Work Environ Health 12(9):27-31. 

*Moulin JJ, Wild P, Mur JM, et al. 1988. Respiratory health assessment by questionnaire of 2024 

workers involved in man-made miner fiber production. Int Arch Occup Environ Health 61(3):171-178. 

*Muhle H, Bellmann B. 1995. Biopersistence of man-made vitreous fibres. Ann Occup Hyg 39(5):655­

660. 

*Muhle H, Bellmann B. 1997. Significance of the biodurability of man-made vitreous fibers to risk 

assessment. Environ Health Perspect 105:1045-1047. 
 

SYNTHETIC VITREOUS FIBERS 254 

9. REFERENCES 

Muhle H, Mangelsdorf I. 2003. Inahalation toxicity of mineral particles: Critical appraisal of endpoints 

and study design. Toxicol Lett 140-141:223-228. 

Muhle H, Pott F. 2000. Asbestos as reference material for fibre-induced cancer. Int Arch Occup Environ 

Health 73:S53-S59. 

Muhle H, Bellmann B, Pott F. 1994. Comparative investigations of the biodurability of mineral fibers in 

the rat lung. Environ Health Perspect 102:163-168. 

*Muhle H, Pott F, Bellman B, Takenaka S, et al. 1987. Inhalation and injection experiments in rats to 

test the carcinogenicity of MMMF. Ann Occup Hyg 31(4B):755-764. 

Murata-Kamiya N, Tsutsui T, Fujino A, et al. 1997. Determination of carcinogenic potential of mineral 

fibers by 8-hydroxydeoxyguanosine as a marker of oxidative DNA damage in mammalian cells. Int Arch 

Occup Environ Health 70:321-326. 

Murphy GB. 1961. Fiber glass pneumoconiosis. Arch Environ Health 3:102-108. 

Musselman R. 1992. A case-control study of lung cancer in a cohort of workers potentially exposed to 

slog wool fibres. Br J Ind Med 49(6):454. 

*Musselman R, Miiller W, Eastes W, et al. 1994a. Biopersistence of crocidolite versus man-made 

vitreous fibers in rat lungs after brief exposures. In: Mohr U, Dungworth DL, Mauderly JL, et al., eds. 

Toxic and carcinogenic effects of solid particles in the respiratory tract. Washington, DC: ILSI Press, 

451-454. 

*Musselman RP, Miiller WC, Eastes W, et al. 1994b. Biopersistences of man-made vitreous fibers and 

crocidolite fibers in rat lungs following short-term exposures. Environ Health Perspect Suppl 102(5):139­

143. 

*Myojo T. 1987. Deposition of fibrous aerosol in model bifurcating tubes. J Aerosol Sci 18(3):337-347. 

Myojo T. 1990. The effect of length and diameter on the disposition of fibrous aerosol in a model lung 

bifurcation. J Aerosol Sci 21(5):651-659. 

Myojo T, Takaya M. 2001. Estimation of fibrous aerosol deposition in upper bronchi based on 

experimental data with model bifurcation. Ind Health 39:141-149. 

Nadeau D, Fouquette-Couture L, Paradis D, et al. 1987. Cytotoxicity of respirable dusts from industrial 

minerals; comparison of two naturally occurring and two man-made silicates. Drug Chem Toxicol 10:49­

86. 

*NAIMA. 2002. Fiber glass and slag wool insulations- materials for a sustainable planet. North 

American Insulation Manufacturers Association. Publication No. 12. 

*NAS/NRC. 1989. Report of the oversight committee. In: Biologic markers in reproductive toxicology. 

Washington, DC: National Academy of Sciences, National Research Council, National Academy Press. 

*Nasr ANM, Ditchek T, Scholtens PA. 1971. The prevalence of radiographic abnormalities in the chests 

of fiber glass workers. J Occup Med 13(8):371-376. 
 

SYNTHETIC VITREOUS FIBERS 255 

9. REFERENCES 

*Navy Environment Health Center. 1997. Man-made vitreous fibers. Technical Manual NEHCTM6290-1. Rev. A. 

Nejjari A, Fournier J, Pezerat H, et al. 1993. Mineral fibres: Correlation between oxidizing surface 

activity and DNA base hydroxylation. Br J Ind Med 50(6):501-504. 

*Newball HH, Brahim SA. 1976. Respiratory response to domestic fibrous glass exposure. Environ Res 

12:201-207. 

*NIOSH. 1976. Occupational exposure to fibrous glass. Proceedings of a Symposium. Washington, 

DC: National Institute for Occupational Safety and Health, 33-61, 83-89, 193-204. 

*NIOSH. 1977. Occupational exposure to fibrous glass-criteria for a recommended standard. National 

Institute for Occupational Safety and Health. 

*NIOSH. 1992. Pocket guide to chemical hazards. National Institute for Occupational Safety and 

Health. 

*NIOSH. 1994a. Asbestos (bulk) by PLM. NIOSH Manual of Analytical Methods (NMAM), Fourth 

Edition, 8/15/94. National Institute for Occupational Safety and Health. 

NIOSH. 1994b. NIOSH manual of analytical methods. NIOSH method 7400. 4th ed. National Institute 

for Occupational Safety and Health. 

*NIOSH. 1999. Work-related lung disease surveillance report 1999. U.S. Department of Health and 

Human Services, Division of Respiratory Disease Studies. National Institute for Occupational Safety and 

Health. Washington, DC. 

*NIOSH. 2002. NIOSH pocket guide to chemical hazards. National Institute for Occupational Safety 

and Health. Wysiwyg://157//http://www.cdc.gov/nIOSH/npg/npg.html. May 07, 2002. 

*NRC. 1993. National Research Council. Pesticides in the diets of infants and children. Washington, 

DC: National Academy Press. 

*NRC Subcommittee on Manufactured Vitreous Fibers. 2000. Review of the U.S. Navy’s Exposure 

Standard for manufactured vitreous fibers. National Academy of Sciences, National Research Council, 

Washington, DC: National Academy Press. 

*NTP. 1994. 7th Report on carcinogens. National Toxicology Program. http://ntpserver.niehs.nih.gov/Main_pages/NTP_7RoC_pg.html. May 07, 2002. 

*NTP. 1998. 8th Report on carcinogens. National Toxicology Program. http://ntpserver.niehs.nih.gov/Main_pages/NTP_8RoC_pg.html. May 07, 2002. 

*NTP. 2000. 9th Report on carcinogens. National Toxicology Program. 

http://ehp.niehs.nih.gov/roc/toc9.html. May 07, 2002. 

*NTP. 2002. 10th Report on carcinogens. National Toxicology Program. 

http://ehp.niehs.nih.gov/roc/toc9.html. January 17, 2004. 
SYNTHETIC VITREOUS FIBERS 256 

9. REFERENCES 

*Oberdörster G. 1994. Respiratory tract dosimetry of particles: implications for setting of exposure 

concentrations and extrapolation modeling. Proceedings of an international symposium: IPCS Joint 

Series No. 18, 83-110. 

*Oberdörster G. 2000. Determinants of the pathogenicity of man-made vitreous fibres (MMVF) Int Arch 

Occup Environ Health 73:S60-S68. 

Oberdörster G. 2002. Toxicokinetics and effects of fibrous and nonfibrous particles. Inhal Toxicol 

14:29-56. 

Ohyama M, Otake T, Morinaga K. 2000. The chemiluminescent response from human monocytederived macrophages exposed to various mineral fibers of different sizes. Ind Health 38(3):289-293. 

Ohyama M, Otake T, Morinaga K. 2001. Effect of size of man-made and natural mineral fibers on 

chemiluminescent response in human monocyte-derived macrophages. Environ Health Perspect 

109(10):1033-1038. 

Ojajarvi IA, Partanen TJ, Ahblom A, et al. 2000. Occupational exposures and pancreatic cancer: A 

meta-analysis. Occup Environ Med 57(5):316-324. 

*Okabe K, Murthy GGK, Vallarino JA, et al. 1997. Deposition efficiency of inhaled fibers in the 

hamster lung. Inhal Toxicol 9(2):85-98. 

Okabe K, Vallarino JA, Murthy GGK, et al. 1996. Dissolution of slagwool fibers in the filter clearing 

and mounting step in preparation for counting. Inhal Toxicol 8(3):263-270. 

Okayasu R, Wu L, Hei TK. 1999. Biological effects of naturally occurring and man-made fibres: in 

vitro cytotoxicity and mutagenesis in mammalian cells. Br J Cancer 79(9/10):1319-1324. 

*Olsen JH, Jensen OM. 1984. Cancer incidence among employees in one mineral wool production plant 

in Denmark. Scand J Work Environ Health 10:17-24. 

*Olsen JH, Jensen OM, Kampstrup O. 1986. Influence of smoking habits and place of residence on the 

risk of lung cancer among workers in one rock-wool producing plant in Denmark. Scand J Work Environ 

Health 12:48-52. 

*Ong T, Lui Y, Zhong B-Z, et al. 1997. Induction of micronucleated and mutinucleated cells by manmade fibers in vitro in mammalian cells. J Toxicol Environ Health 50(4):409-414. 

Osgood CJ. 1994. Refractory ceramic fibers (RFCs) induce germline aneuploidy in Drosophila oocytes. 

Mutat Res 324(1-2):23-27. 

*OSHA. 1992. U.S. Department of Labor, Occupational Safety and Health Administration. 57:7877­

7878, 24310-24331, 49657-49661. 

*OSHA. 1999. OSHA endorses major agreement to protect workers exposed to fiberglass insulation. 

Occupational Safety and Health Administration. http://www.osha-slc.gov/media/oshanews/may99/trade19990518.html. May 07, 2002. 
 

SYNTHETIC VITREOUS FIBERS 257 

9. REFERENCES 

OSHA. 2001a. Asbestos. Occupational safety and health standards. Occupational Safety and Health 

Administration. Code of Federal Regulations. 29 CFR 1910.1001. 

http://www.osha.gov/pls/oshaweb/owa...ARDS&p-id=9995&p-text-version=FALSE. May 07, 2002. 

*OSHA. 2001b. Synthetic mineral fibers. Occupational Safety and Health Administration. 

http://www.osha.gov/SLTC/syntheticmineralfibers/index.html. May 07, 2002. 

*OSHA. 2002. Synthetic mineral fibers. Occupational Safety and Health Administration. 

http://www.osha.gov/oshinfo/priorities/synthetic.html. May 07, 2002. 

*Oshimura M, Hesterberg TW, Tsutsui T, et al. 1984. Correlation of asbestos-induced cytogenic effects 

with cell transformation of Syrian hamster embryo cells in culture. Cancer Res 44(11):5017-5022. 

*Owen GM, Brozek J. 1966. Influence of age, sex and nutrition on body composition during childhood 

and adolescence. In: Falkner F, ed. Human development. Philadelphia, PA: WB Saunders, 222-238. 

Pang TWS. 2000. Precision and accuracy of asbestos fiber counting by phase contrast microscopy. 

Environ Sci Technol 61(4):529-538. 

*Pang TWS, Schonfeld-Starr FA, Patel K. 1989. An improved membrane filter technique for evaluation 

of asbestos fibers. Am Ind Hyg Assoc J 50(3):174-190. 

Pelin K, Kivipensas P, Linnainmaa K. 1995. Effects of asbestos and man-made vitreous fibers on cell 

division in cultured human mesothelial cells in comparison to rodent cells. Environ Mol Mutagen 

25:118-125. 

*Peraud A, Riebe-Imre M. 1994. Toxic and chromosomal-damaging effects of natural and man-made 

mineral fibers in epithelial lung cells in vitro. In: Dungworth DL, Mauderly JL, Oberdorster G, eds. 

Toxic and carcinogenic effects of solid particles in the respiratory tract. Washington, DC: ILSI Press, 

569-574. 

*Perrault G, Dion C, Cloutier Y. 1992. Sampling and analysis of mineral fibers on construction sites. 

Appl Occup Environ Hyg 7(5):323-326. 

*Petersen R, Sabroe S. 1991. Irritative symptoms and exposure to mineral wool. Am J Ind Med 

20(1):113-122. 

*Phalen RF, Oldham MJ, Beaucage CB, et al. 1985. Postnatal enlargement of human tracheobronchial 

airways and implications for particle deposition. Anat Rec 212:368-380. 

*Pickrell JA, Hill JO, Carpenter RL, et al. 1983. In vitro and in vivo response after exposure to manmade mineral and asbestos insulation fibers. Am Ind Hyg Assoc J 44(8):557-561. 

Pigott GH, Ishmael J. 1981. An assessment of the fibrogenic potential of 2 refractory fibers by 

intraperitoneal injection in rats. Toxicol Lett 8(3):153-164. 

Pigott GH, Ishmael J. 1992. The effects of intrapleural injections of alumina and aluminosilicate 

(ceramic) fibers. Int J Exp Pathol 73:137-146. 
 

SYNTHETIC VITREOUS FIBERS 258 

9. REFERENCES 

*Plato N, Gustavsson P, Krantz S. 1997. Assessment of past exposure to man-made vitreous fibers in the 

Swedish prefabricated house industry. Am J Ind Med 32(4):349-354. 

Plato N, Krantz S, Andersson L, et al. 1995a. Characterization of current exposure to man-made vitreous 

fibres (MMVF) in the prefabricated house industry in Sweden. Ann Occup Hyg 39(2):167-179. 

Plato N, Krantz S, Gustavsson P, et al. 1995b Fiber exposure assessment in the Swedish rock wool and 

slag wool production industry in 1938-1990. Scand J Work Environ Health 21(5):345-352. 

*Plato N, Westerholm P, Gustavsson P, et al. 1995c. Cancer incidence, mortality and exposure-response 

among Swedish man-made vitreous fiber production workers. Scand J Work Environ Health 21(5):353­

361. 

*Pohlabein H, Jockel K-H, Bruske-Hohlfeld I, et al. 2000. Lung cancer and exposure to man-made 

vitreous fibers: Results from a pooled case-control study in Germany. Am J Ind Med 37:469-477. 

*Possick PA, Gellin GA, Key MM. 1970. Fibrous glass dermatitis. Am Ind Hyg Assoc J 37:12-15. 

Pott F. 1980. Animal experiments on biological effects of mineral fibres. In: Wagner JC, Davis W, eds. 

Biological effects of mineral fibers. IARC Sci Publ 30:261-272. 

Pott F. 1995. Detection of mineral fibre carcinogenicity with the intraperitoneal test recent results and 

their validity. Ann Occup Hyg 39(5):771-779. 

Pott F, Roller M. 1998. [How far can carcinogenicity studies of fiber types be substituted by data on 

their biopersistence?] Geharstoffe Reinhalt Luft 58(3):85-91. (German) 

Pott F, Dungworth DL, Heinrich U, et al. 1994. Lung tumours in rats after intratracheal instillation of 

dusts. Ann Occup Hyg 38:357-363. 

Pott F, Friedrichs KH, Huth F. 1975. [Carcinogenic effects of fibrous dusts.] EUR 2:715-724. 

(German) 

*Pott F, Freidrichs K-H, Huth F. 1976. Results of animal experiments concerning the carcinogenic effect 

of fibrous dusts and their interpretation with regard to the carcinogenesis in humans. Zbl Bakt Hyg I Abt 

Orig B 162:467-505. 

Pott F, Huth F, Friedrichs KH. 1974. Tumorigenic effect of fibrous dusts in experimental animals. 

Environ Health Perspect 9:313-315. 

Pott F, Huth F, Spurny K. 1980. Tumour induction after intraperitoneal injection of fibrous dusts. In: 

Wagner JC, Davis W, eds. Biological effects of mineral fibres. IARC Sci Publ 30:337-342. 

Pott F, Roller M, Kamino K, et al. 1994. Significance of durability of mineral fibers for their toxicity 

and carcinogenic potency in the abdominal cavity of rats in comparison with the low sensitivity of 

inhalation studies. Environ Health Perspect 102:145-150. 

Pott F, Roller M, Ziem U, et al. 1989. Carcinogenicity studies on natural and man-made fibres with the 

intraperitoneal test in rats. IARC Sci Publ 90:173-179. 
 

SYNTHETIC VITREOUS FIBERS 259 

9. REFERENCES 

*Pott F, Schllipkoter HW, Ziem U. 1984. New results from implantation experiments with mineral 

fibres. Proceedings of the World Health Organization Conference, 286-302. 

Pott F, Ziem U, Mohr U. 1983. Lung carcinomas and mesotheliomas following intratracheal instillation 

of glass fibres and asbestos. Report held on the VIth International Pneumoconiosis Conference, 

September 20-23, 1983. 

*Pott F, Ziem L, Reiffer FJ, et al. 1987. Carcinogenicity studies on fibres, metal compounds, and some 

other dusts in rats. Exp Pathol 32:129-152. 

*Potter RM, Mattson SM. 1991. Glass fibre dissolution in a physiological saline solution. Glastech Ber 

64:16-28. 

*Quinn MM, Smith TJ, Youk AO, et al. 2001. Historical cohort study of US man-made vitreous fiber 

production workers: VIII. Exposure-specific job analysis. J Occup Environ Med 43:824-834. 

Randall REG, DuToit RSJ. 1994. The retention and clearance of glass fibre and different varieties of 

asbestos by the lung. Ann Occup Hyg 38:757-761. 

*Renne RA, Eldridge SR, Lewis TR, et al. 1985. Fibrogenic potential of intratracheally instilled quartz, 

ferric oxide, fibrous glass, and hydrated alumina in hamsters. Toxicol Pathol 13:306-314. 

Rice CH, Lockey JE, Lemasters GK, et al. 1997. Estimation of historical and current employee exposure 

to refractory ceramic fibers during manufacturing and related operations. Appl Occup Environ Hyg 

12(1):54-61. 

Riebe-Imre M, Aufderheide M, Emura M, et al. 1994. Comparative studies with natural and man-made 

mineral fibres in vitro and in vivo. NATO ASI Ser H 85:273-284. 

*Rindel A, Bach E, Breum NO, et al. 1987. Correlating health effects with indoor air quality in 

kindergartens. Int Arch Occup Environ Health 59:363-373. 

*Robinson CF, Dement JM, Ness GO, et al. 1982. Mortality patterns of rock and slag mineral wool 

production workers: an epidemiological and environmental study. Br J Ind Med 39(1):45-53. 

*Rodelsperger K, Woitowitz HJ. 1995. Airborne fibre concentrations and lung burden compared to the 

tumour response in rats and humans exposed to asbestos. Ann Occup Hyg 39(5):719-725. 

*Rodelsperger K, Jockel K-H, Pohlabein H, et al. 2001. Asbestos and man-made vitreous fibers as risk 

factors for diffuse malignant mesothelioma: Results from a German hospital-based case-control study. 

Am J Ind Med 39(3):262-275. 

*Roggli VL. 1989. Nonasbestos mineral fibers in human lungs. Microbeam Analysis 24:57-59. 

Roller M, Pott F, Kamino K, et al. 1996. Results of current intraperitoneal carcinogenicity studies with 

mineral and vitreous fibres. Exp Toxicol Pathol 48:3-12. 

Roller M, Pott F, Kamino K, et al. 1997. Dose-response relationship of fibrous dusts in intraperitoneal 

studies. Environ Health Perspect Suppl 105(5):1253-1256. 
SYNTHETIC VITREOUS FIBERS 260 

9. REFERENCES 

Rood AP. 1988. Size distribution of airborne ceramic fibres as determined by transmission electron 

microscopy. Ann Occup Hyg 32(2):237-240. 

Rood AP, Streeter RR. 1985. Size distributions of airborne superfine man-made mineral fibers 

determined by transmission electron microscopy. Am Ind Hyg Assoc J 46(5):257-261. 

Rossiter CE. 1993. Pulmonary effects of exposure to fine fiberglass: irregular opacities and small 

airways obstruction. Br J Ind Med 50:382-383. 

*Rossiter CE, Gilson JC, Sheers G, et al. 1994. Refractory ceramic fibre production workers. Analysis 

of radiograph readings. Ann Occup Hyg 38:731-738. 

Rouyer E, Lehuede P, Chopinet M-H. 1995. Corrosion mechanisms of glass fibers by physiological fluid 

in in-vitro tests. Verre 1:621-624. 

Rowe JN, Springer JA. 1986. Asbestos lung cancer risks: Comparison of animal and human 

extrapolations. Risk Anal 6(2):171-180. 

Ruotsalainen M, Hirvonen M-R, Luoto K. 1999. Production of reactive oxygen species by man-made 

vitreous fibres in human polymorphonuclear leukocytes. Hum Exp Toxicol 18(6):354-362. 

Rutten A, Bermudez E, Mangum J, et al. 1994a. Pleural pathology in hamsters and rats exposed to 

instilled man-made vitreous fibers. In: Dungworth DL, Mauderly JL, Oberdorster G, eds. Toxic and 

carcinogenic effects of solid particles in the respiratory tract. Washington, DC: ILSI Press, 595-598. 

Rutten AA, Bermudez E, Mangum JB, et al. 1994b. Mesothelial cell proliferation induced by 

intrapleural instillation of man-made fibers in rats and hamsters. Fundam Appl Toxicol 23(1):107-117. 

Saffiotti U. 1998. Respiratory tract carcinogenesis by mineral fibres and dusts: models and mechanisms. 

Monaldi Arch Chest Dis 53(2):160-167. 

Sahle W, Laszlo I. 1996. Airborne inorganic fibre level monitoring by transmission electron microscope 

(TEM): Comparison of direct and indirect sample transfer methods. Ann Occup Hyg 40(1):29-44. 

*Sali D, Boffetta P, Andersen A, et al. 1999. Non-neoplastic mortality of European workers who 

produce man made vitreous fibres. Occup Environ Med 56:612-617. 

*Sanden A, Jarvholm B. 1986. Pleural plaques, respiratory symptoms and respiratory function in 

shipyard workers exposed to man-made mineral fibres. J Soc Occup Med 36:86-89. 

Saracci R. 1986. Ten years of epidemiologic investigations on man-made mineral fibers and health. 

Scand J Work Environ Health 12:5-11. 

*Saracci R, Simonato L, Acheson ED, et al. 1984. Mortality and incidence of cancer of workers in the 

man made vitreous fibres producing industry: an international investigation at 13 European plants. Br J 

Ind Med 41:425-436. 

*Scansetti G, Pira E, Botta GC, et al. 1993. Asbestos exposure in a steam-electric generating plant. Ann 

Occup Hyg 37(6):645-655. 
 

 

 

 

SYNTHETIC VITREOUS FIBERS 261 

9. REFERENCES 

*Schneider T. 1986. Manmade mineral fibers and other fibers in the air and settled dust. Environ Int 

12:61-65. 

Schneider T, Skotte J. 1990. Fiber exposure reassessed with the new indices. Environ Res 51:108-116. 

*Schneider T, Stokholm J. 1981. Accumulation of fibres in the eyes of workers handling man-made 

mineral fiber products. Scand J Work Environ Health 7(7):271-276. 

*Schneider T, Burdett G, Martinon L, et al. 1996. Ubiquitous fiber exposure in selected sampling sites in 

Europe. Scand J Work Environ Health 22(4):274-284. 

Schneider T, Gibbs GW, Burdett G, et al. 1997. Testing fibre release from insulation products: Report 

on a workshop. Ann Occup Hyg 41(5):605-607. 

Schneider T, Husemoen T, Olsen E, et al. 1993. Airborne fibre concentration during standardized 

building insulation with bonded man-made vitreous fibre insulation material having different nominal 

diameters and oil content. Ann Occup Hyg 37(6):631-644. 

*Schneider T, Nielsen O, Bredsdorff P, et al. 1990. Dust in buildings with man-made mineral fiber 

ceiling boards. Scand J Work Environ Health 16:434-439. 

Schneider T, Skotte J, Nissen P. 1985. Man-made mineral fiber size fractions and their interrelation. 

Scand J Work Environ Health 11(2):117-122. 

*Scholze H, Conradt R. 1987. An in vitro study of the chemical durability of siliceous fibres. Ann 

Occup Hyg 31(4B):683-692. 

Schuman LD, Infante PF. 1993. Synthetic mineral fibers. J Occup Med 35(12):1173-1177. 

*Searl A. 1997. A comparative study of the clearance of respirable para-aramid, chrysotile and glass 

fibres from rat lungs. Ann Occup Hyg 41:217-233. 

Searl A, Cullen RT. 1997. An enzymatic tissue digestion method for fibre biopersistence studies. Ann 

Occup Hyg 41(6):721-727. 

*Searl A, Buchanan D, Cullen RT, et al. 1999. Biopersistence and durability of nine mineral fibre types 

in rat lungs over 12 months. Ann Occup Hyg 43(3):143-153. 

*Sebastien P, Vergnon JM, Blanchard O, et al. 1994. Durability of ceramic fibres in the human lung. 

Preliminary results. Ann Occup Hyg 38:723-730. 

Sernau R, Cortina T, Zito M, et al. 1984. Genotoxicity of asbestos and fiberglass in the Chinese hamster 

ovary (CHO) HGRPT forward mutation and sister chromatid exchange assays. Environ Mutagen 6:422­

423. 

*Setchell BP, Waites GMH. 1975. The blood-testis barrier. In: Creep RO, Astwood EB, Geiger SR, 

eds. Handbook of physiology: Endocrinology V. Philadelphia, PA: WB Saunders, 222-238. 

*Shannon HS, Hayes M, Julian JA, et al. 1984. Mortality experience of glass fibre workers. Br J Ind 

Med 41:35-38. 
 

SYNTHETIC VITREOUS FIBERS 262 

9. REFERENCES 

*Shannon HS, Jamieson E, Julian JA, et al. 1987. Mortality experience of Ontario glass fibre workers - 

extended follow-up. Ann Occup Hyg 31(4B):657-662. 

*Shannon HS, Jamieson E, Julian JA, et al. 1990. Mortality of glass filament (textile) workers. Br J Ind 

Med 47(5):533-536. 

Shaw GR, Connell DW. 1994. Prediction and monitoring of the carcinogenicity of polycyclic aromatic 

compounds (PACs). Rev Environ Contam Toxicol 135:1-62. 

*Simonato L, Fletcher AC, Cherrie J, et al. 1986a. The man-made mineral fiber European historical 

cohort study. Scand J Work Environ Health 12:34-47. 

Simonato L, Fletcher AC, Cherrie J, et al. 1986b. Updating lung cancer mortality among a cohort of 

man-made mineral fibre production workers in seven European countries. Cancer Lett 30(2):189-200. 

*Simonato L, Fletcher AC, Cherrie JW, et al. 1987. The International Agency for Research on Cancer 

historical cohort study of MMMF production workers in seven European countries: Extension of the 

follow-up. Ann Occup Hyg 31(4B):603-623. 

*Sincock AM, Delhanty JDA, Casey G. 1982. A comparison of the cytogenetic response to asbestos and 

glass fibre in Chinese hamster and human cell lines. Mutat Res 101(3):257-268. 

*Sjogren B. 2000. Non-neoplastic mortality of European workers who produce man-made vitreous 

fibres. Occup Environ Med 57:284-288. 

*Smith DM, Ortiz LW, Archuleta RF, et al. 1987. Long-term health effects in hamsters and rats exposed 

chronically to man-made vitreous fibres. Ann Occup Hyg 31(4B):731-754. 

*Smith TJ, Quinn MM, Marsh GM, et al. 2001. Historical cohort study of US man-made vitreous fiber 

production workers: VII. Overview of the exposure assessment. J Occup Environ Med 43(9):809-823. 

*Spruny KR. 1994. Sampling, analysis, identification and monitoring of fibrous dusts and aerosols. 

Analyst 119:41-51. 

Spurny KR, Pott F, Stober W, et al. 1983. On the chemical changes of asbestos fibers and MMMFs in 

biologic residence and in the environment: Part I. Am Ind Hyg Assoc J 44(11):833-845. 

*Stam-Westerveld EB, Coenraads PJ, vanderValk PGM, et al. 1994. Rubbing test responses of the skin 

to man-made mineral fibres of different diameters. Contact Dermatitis 31:1-4. 

*Stanton MF, Wrench C. 1972. Mechanisms of mesothelioma induction with asbestos and fibrous glass. 

J Natl Cancer Inst 48:797-822. 

*Stanton WF, Layard M, Tegeris A, et al. 1977. Carcinogenicity of fibrous glass: Pleural response in 

the rat in relation to fiber dimension. J Natl Cancer Inst 58(3):587-597. 

Steenland K, Stayner L. 1997. Silica, asbesots, man-made mineral fibers, and cancer. Cancer Causes 

Control 8:491-503. 
 

 

SYNTHETIC VITREOUS FIBERS 263 

9. REFERENCES 

*Stöber W. 1972. Dynamic shape factors of nonspherical aerosol particles. In: Mercer TT, Morrow PE, 

Stober W, eds. Assessment of airborne particles. Springfield: Charles C. Thomas, 249-289. 

*Stöber W, McClellan, RO. 1997. Pulmonary retention and clearance of inhaled biopersistent aerosol 

particles: Data-reducing interpolation models and models of physiologically based systems. Crit Rev 

Toxicol 27(6):539-598. 

*Stockholm J, Norn M, Schneider T. 1982. Ophthalmologic effects of man-made mineral fibers. Scand 

J Work Environ Health 8(3):185-190. 

Stone RA, Marsh GM, Youk AO, et al. 1996. Statistical estimation of exposure to fibres in jobs for 

which no direct measurements are available. Occup Hyg 3:91-101. 

*Stone RA, Youk AO, Marsh GM, et al. 2001. Historical cohort study of US man-made vitreous fiber 

production workers: IV Quantitative exposure-response analysis of the nested case-control study of 

respiratory system cancer. J Occup Environ Med 43(9):779-792. 

Strubel G, Fraij B, Rodelsperger K, et al. 1986. Man-made mineral fibers in the working environment. 

Letter to the editor. Am J Ind Med 10(1):101-102. 

*Switala ED, Harlan RC, Schlaudecker DG, et al. 1994. Measurement of respirable glass and total fiber 

concentrations in the ambient air around a fiberglass wool manufacturing facility and a rural area. Regul 

Toxicol Pharmacol 20(3 part 2):S76-S88. 

Takahashi T, Munakata M, Takekawa H, et al. 1996. Pulmonary fibrosis in a carpenter with long-lasting 

exposure to fiberglass. Am J Ind Med 30:596-600. 

Tanaka I, Oyabu T, Ishimatsu S. 1994a. Pulmonary deposition and clearance of glass fiber in rat lungs 

after long-term inhalation. Environ Health Perspect 102:215-216. 

Tanaka I, Shutou T, Ishimatsu S. 1994b. Pulmonary deposition and clearance of glass fibre in rats after 

continuous inhalation. Ann Occup Hyg 38:753-756. 

Tanaka I, Yamato H, Oyabu T, et al. 2001. Biopersistence of man-made fibers by animal inhalation 

experiments in recent reports. Ind Health 39(2):114-118. 

*Tarvainen K, Jolanki R, Forsman-Gronholm L, et al. 1993. Exposure, skin protection and occupational 

skin diseases in the glass-fibre-reinforced plastics industry. Contact Dermatitis 29(3):119-127. 

*Teppo L, Kojonen E. 1986. Mortality and cancer risk among workers exposed to man-made mineral 

fibers in Finland. Scand J Work Environ Health 12:61-64. 

*Thriene B, Sobottka A, Willer H, et al. 1996. Man-made mineral fibre boards in buildings- health risks 

caused by quality deficiencies. Toxicol Lett 88(1-3):299-303. 

*TIMA Inc. 1993. Man-made vitreous fibers: Nomenclature, chemical and physical properties, 

Stamford, CT: TIMA Inc., 1-70. 

*Timbrell V. 1965. The inhalation of fibrous dusts. Ann N Y Acad Sci 132:255-273. 
 

SYNTHETIC VITREOUS FIBERS 264 

9. REFERENCES 

Timbrell V. 1972. Inhalation and biological effects of asbestos. In: Mercer TT, Morrow PE, Stober W, 

eds. Assessment of airborne particles fundamentals, applications and implications to inhalation toxicity. 

Springfield, IL: Charles C Thomas, 429-445. 

*Timbrell V. 1982. Deposition and retention of fibres in the human lung. Ann Occup Hyg 26(1-4):347­

369. 

Tran CL, Jones AD, Miller BG, et al. 2003. Modeling the retention and clearance of manmade vitreous 

fibers in the rat lung. Inhal Toxicol 15:553-587. 

*Trethowan WN, Burge PS, Rossiter CE. 1995. Study of the respiratory health of employees in seven 

European plants that manufacture ceramic fibres. Occup Environ Med 52:97-104. 

*TRI01. 2003. TRI explorer: Providing access to EPA’s toxics release inventory data. Washington, 

DC: Office of Information Analysis and Access. Offices of Environmental Information. U.S. 

Environmental Protection Agency. Toxic Release Inventory. http://www.epa.gov/triexplorer/. May 08, 

2001. 

Tsuda T, Morimoto Y, Yamato H, et al. 1997. Effects of mineral fibers on the expression of genes 

whose product may play a role in fiber pathogenesis. Environ Health Perspect Suppl 105(5):1173-1178. 

*Tsuda A, Stringer BK, Mijailovich SM, et al. 1999. Alveolar cell stretching in the presence of fibrous 

particles induces interleukin-8 responses. Am J Respir Cell Mol Biol 21:455-462. 

*Turim J, Brown RC. 2003. A dose-response model for refractory ceramic fibers. Inhal Toxicol 

15:1103-1118. 

Unfried K, Roller M, Pott F, et al. 1997. Fiber-specific molecular features of tumors induced in rat 

peritoneum. Environ Health Perspect Suppl 105(5):1103-1108. 

*USDOC. 2002. US General exports and imports. United States Department of Commerce. 

USITC. 1995. Industry and trade summary. Manmade fibers. USITC Publication 2874. 

Valberg PA, Blanchard JD. 1991. Pulmonary macrophage physiology: Origin, motility, endocytosis. 

In: Parent RA, ed. Comparative biology of the normal lung. Vol 1, Chapter 36. Boca Raton, FL: CRC 

Press, Inc. 

*Vallarino J, Spengler JD, Buck R, et al. 2003. Quantifying synthetic vitreous fiber surface 

contamination in office buildings. Am Ind Hyg Assoc J 64:80-87. 

van den Bergen EA, Rocchi PSJ, Boogaard PJ. 1994. Ceramic fibers and other respiratory hazards 

during the renewal of the refractory lining in a large industrial furnace. Appl Occup Environ Hyg 

9(1):32-35. 

Van Graft M, Spit BJ, Immel HR, et al. 1986. Pulmonary response of hamsters to fibrous glass. 

Clearance and morphology after a single intratracheal instillation. Exp Pathol 29(4):197-209. 

VanOrden DR. 2000. Counting rules for vitreous fiber exposures. Am Ind Hyg Assoc J 61(4):454. 
 

SYNTHETIC VITREOUS FIBERS 265 

9. REFERENCES 

*Veblin DR, Wylie AG. 1993. Mineralogy of amphiboles and 1:1 layer silicates. In: Gutherie GD, 

Mossman BT, eds. MSA reviews in mineralogy, Volume 28. Health effects of mineral dusts, 61-137. 

*Vieira I, Sonnier M, Cresteil T. 1996. Developmental expression of CYP2E1 in the human liver: 

Hypermethylation control of gene expression during the neonatal period. Eur J Biochem 238:476-483. 

Vu VT. 1994. Assessment of the potential health effects of natural and man-made fibers and their testing 

needs: Perspectives of the U.S. Environmental Protection Agency. In: Dungworth DL, Mauderly JL, 

Oberdörster G, eds. Toxic and carcinogenic effects of solid particles in the respiratory tract. Washington, 

DC: ILSI Press, 367-384. 

Vu VT, Dearfield KL. 1993. Biological effects of fibrous materials in experimental studies and related 

regulatory aspects. In: Warheit D, ed. Fiber toxicology. Chapter 18. San Diego, CA: Academic Press, 

Inc., 449-492. 

Vu VT, Lai DY. 1997. Approaches to characterizing human health risks of exposure to fibers. Environ 

Health Perspect 105: 1329-1336. 

Wagner JC, Berry G, Timbrell V. 1973. Mesotheliomata in rats after inoculation with asbestos and other 

materials. Br J Cancer 28(2):173-185. 

Walker AM, Maxim LD, Utell M. 2002. Risk analysis for mortality from respiratory tumors in a cohort 

of refractory ceramic fiber workers. Regul Toxicol Pharmacol 35(1):95-104. 

Wang Q-E, Han C-H, Wu W-D, et al. 1999a. Biological effects of man-made mineral fibers (1) Reactive 

oxygen species production and calcium homeostasis in alveolar macrophages. Ind Health 37(1):62-67. 

*Wang Q-E, Han C-H, Yang Y-P, et al. 1999b. Biological effects of man-made mineral fibers (II) Their 

genetic damages examined by in vitro assay. Ind Health 37(3):342-347. 

*Wardenbach P, Pott F, Woitowitz H-J. 2000. Differences between the classification of man-made 

vitreous fibers (MMVF) according to the European directive and German legislation: analysis of 

scientific data and implications for worker protection. Eur J Oncol 5:111-118. 

Warheit DB. 1989. Interspecies comparisons of lung responses to inhaled particles and gases. CRC Crit 

Rev Toxicol 20:1-29. 

Warheit DB, Hart GA, Hesterberg TW, et al. 2001. Potential pulmonary effects of man-made organic 

fiber (MMOF) dusts. Crit Rev Toxicol 31(6):697-736. 

*Wastiaux A, Blanchard O, Honnons S. 1994. Possible application of urinary analysis to estimate 

dissolution of some man-made vitreous fibers. Environ Health Perspect 102:217-219. 

Waterman LS, Purnell CJ, Anderson PWP. 1992. Airborne fibre levels associated with the use of 

MMMF brazing mats during welding operations. Ann Occup Hyg 34(1):97-99. 

*Watkins DK, Chiazze L, Fryar C. 1997. History cohort mortality study of a continuous filament 

fiberglass manufacturing plant. II. Women and minorities. J Occup Environ Med 39(6):548-555. 
 

SYNTHETIC VITREOUS FIBERS 266 

9. REFERENCES 

Wedge R, Abt E, Bakshi K, et al. 2001. Review of the U.S. Navy's exposure standard for manufactured 

vitreous fibers. Inhal Toxicol 12(1):103-108. 

*Weill H, Hughes JM, Hammad YY, et al. 1983. Respiratory health in workers exposed to man-made 

vitreous fibers. Am Rev Respir Dis 128:104-112. 

Weiss W. 1993. Pulmonary effects of exposure to fine fibreglass: irregular opacities and small airways 

obstruction. Correspondence. Br J Ind Med 50:1054. 

Weiss W. 1996. Epidemiology of fibrous glass and lung cancer: Letter to the editor. Am J Ind Med 

30:105-108. 

*West JR, Smith HW, Chasis H. 1948. Glomerular filtration rate, effective renal blood flow, and 

maximal tubular excretory capacity in infancy. J Pediatr 32:10-18. 

*Westerholm P, Bolander A-M. 1986. Mortality and cancer incidence in the man-made mineral fiber 

industry in Sweden. Scand J Work Environ Health 12 (Suppl 1):78-84. 

*WHO. 1985. Reference methods for measuring synthetic mineral fibers (MMMF). WHO/EURO 

Technical Committee for evaluating MMMF. WHO, Copenhagen. 

*WHO. 1988. Man-made mineral fibers. Environmental Health Criteria. Vol. 77. Geneva: World 

Health Organization. 

*Whong W-Z, Gao H-G, Zhou G, et al. 1999. Genetic alterations of cancer-related genes in glass fiberinduced transformed cells. J Toxicol Environ Health A 56(6):397-404. 

*Widdowson EM, Dickerson JWT. 1964. Chemical composition of the body. In: Comar CL, Bronner 

F, eds. Mineral metabolism: An advanced treatise. Volume II. The elements Part A. New York: 

Academic Press. 

*Wilson R, Langer AM, Nolan RP. 1999. A risk assessment for exposure to glass wool. Regul Toxicol 

Pharmacol 30:96-109. 

Wong O, Musselman RP. 1994. An epidemiological and toxicological evaluation of the carcinogenicity 

of man-made vitreous fiber, with a consideration of coexposures. J Environ Pathol Toxicol 13(3):169­

180. 

*Wong O, Foliart D, Trent LS. 1991. A case-control study of lung cancer in a cohort of workers 

potentially exposed to slag wool fibres. Br J Ind Med 48:818-824. 

Woodworth CD, Mossman BT, Craighead JE. 1983. Induction of squamous metaplasia in organ cultures 

of hamster trachea by naturally occurring and synthetic fibers. Cancer Res 43:4906-4912. 

*Wright GW. 1968. Airborne fibrous glass particles. Arch Environ Health 16:175-181. 

*Wright GW, Kuschner M. 1977. The influence of varying lengths of glass and asbestos on tissue 

response in guinea pigs. Ann Occup Hyg 2:455-474. 
SYNTHETIC VITREOUS FIBERS 267 

9. REFERENCES 

Wu J-D, Milton DK, Hammond K, et al. 1999. Hierarchical cluster analysis applied to workers' 

exposures in fiberglass insulation manufacturing. Ann Occup Hyg 43(1):43-55. 

*Wylie AG, Verkouteren JR. 2000. Amphibole asbestos from Libby, Montana: aspects of 

nomenclature. Am Mineral 85:1540-1542. 

Xie C, Reusse A, Dai J, et al. 2000. TNF-α increases tracheal epithelial asbestos and fiberglass binding 

via a NF-kB-dependent mechanism. Am J Physiol Lung Cell Mol Physiol 2000:L608-L614. 

*Xu GB, Yu CP. 1986. Effects of age on deposition of inhaled aerosols in the human lung. Aerosol Sci 

Technol 5:349-357. 

Yamato H, Tanaka I, Higashi T, et al. 1992. Determinant factor for clearance of ceramic fibres from rat 

lungs. Br J Ind Med 49(3):182-185. 

Yamato H, Tanaka I, Higashi T, et al. 1994. Clearance of inhaled ceramic fibers from rat lungs. Environ 

Health Perspect 102:169-171. 

Yegles M, Janson X, Dong HY, et al. 1995. Role of fibre characteristics on cytotoxicity and induction of 

anaphase/telophase aberrations in rat pleural mesothelial cells in vitro: correlations with in vivo animal 

findings. Carcinogenesis 16(11):2751-2758. 

*Yokosaki Y, Morimoto Y, Yamato H, et al. 1991. Cellular changes induced in rats lungs by inhalation 

of ceramic fibres. Toxicol Ind Health 7(5-6):479-483. 

*Youk AO, Marsh GM, Stone RA, et al. 2001. Historical cohort study of US man-made vitreous fiber 

production workers: III. Analysis of exposure-weighted measures of respirable fibers and formaldehyde 

in the nested case-control study of respiratory system cancer. J Occup Environ Med 43(9):767-778. 

*Yu CP, Oberdörster G. 2000. Dose-response and human cancer and non-cancer risk assessment of 

inhaled refractory ceramic fibers (RCF). Unpublished report to Dr. David Y. Lai. Washington, DC: U.S. 

Envirronmental Protection Agency. 

Yu CP, Asgharian B, Yen BM. 1986. Impaction and sedimentation deposition of fibers in airways. Am 

Ind Hyg Assoc J 47(2):72-77. 

*Yu CP, Dai T, Boymel PM, et al. 1998a. A clearance model of man-made vitreous fibers (MMVFs) in 

the rat lung. Inhal Toxicol 10(4):253-274. 

*Yu CP, Dai YT, Ding YJ. 1998b. A retention model of man-man vitreous fibers (MMVFs) inhaled by 

rats. Aerosol Sci Technol 29(2):152-162. 

*Yu, CP, Ding J, Zhang L, et al. 1995b. Deposition and clearance modeling of inhaled kaolin refractory 

ceramic fibers (RCF) in hamsters- comparison between species. Inhal Toxicol 7(2):165-177. 

*Yu CP, Ding YJ, Zhang L, et al. 1996. A clearance model of refractory ceramic fibers (RCF) in the rat 

lung including fiber dissolution and breakage. J Aerosol Sci 27(1):151-159. 

*Yu C, Ding Y, Zhang L, et al. 1997. Retention modeling of refractory ceramic fibers (RCF) in humans. 

Regul Toxicol Pharmacol 25:18-25. 
SYNTHETIC VITREOUS FIBERS 268 

9. REFERENCES 

*Yu CP, Zhang L, Oberdörster G, et al. 1994. Clearance of refractory ceramic fibers (RCF) from the rat 

lung: Development of a model. Environ Res 65(2):243-253. 

*Yu CP, Zhang L, Oberdörster G, et al. 1995a. Deposition of refractory ceramic fibers (RCF) in the 

human respiratory tract and comparison with rodent studies. Aerosol Sci Technol 23:291-300.
 

Zanjanian MH, Sahu A 1981. Anaphylactic reaction to fiber glass. Ann Allergy 47:157-158. 

*Zhong B-Z, Ong T, Whong W-Z. 1997. Studies on the relationship between treatment condition and 

micronucleus induction in V79 cells exposed to silica and glass fibers. Mutat Res 39:111-116. 

*Ziegler EE, Edwards BB, Jensen RL, et al. 1978. Absorption and retention of lead by infants. Pediatr 

Res 12:29-34. 

*Zoitos BK, DeMeringo A, Rouyer E, et al. 1997. In vitro measurement of fiber dissolution rate relevant 

to biopersistence at neutral pH: An interlaboratory round robin. Inhal Toxicol 9:525-540. 

Zoller T, Zeller WJ. 2000. Production of reactive oxygen species by phagocytic cells after exposure to 

glass wool and stone wool fibres -effect of fibre preincubation in aqueous solution. Toxicol Lett 114:1-9. 

*Zoltai, T. 1979. Asbestiform and acicular mineral fragments. Ann NY Acad Sci 330:621-643. 

*Zoltai T. 1981. Amphibole asbestos mineralogy. In: Veblen DR, ed. Amphiboles and other hydrous 

particles. MSA reviews in mineralogy. Volume 28, 235-278. 
SYNTHETIC VITREOUS FIBERS 269 

10. GLOSSARY 

Absorption—The taking up of liquids by solids, or of gases by solids or liquids. 

Acute Exposure—Exposure to a chemical for a duration of 14 days or less, as specified in the 

Toxicological Profiles. 

Adsorption—The adhesion in an extremely thin layer of molecules (as of gases, solutes, or liquids) to the 

surfaces of solid bodies or liquids with which they are in contact. 

Adsorption Coefficient (Koc)—The ratio of the amount of a chemical adsorbed per unit weight of 

organic carbon in the soil or sediment to the concentration of the chemical in solution at equilibrium. 

Adsorption Ratio (Kd)—The amount of a chemical adsorbed by sediment or soil (i.e., the solid phase) 

divided by the amount of chemical in the solution phase, which is in equilibrium with the solid phase, at a 

fixed solid/solution ratio. It is generally expressed in micrograms of chemical sorbed per gram of soil or 

sediment. 

Benchmark Dose (BMD)—Usually defined as the lower confidence limit on the dose that produces a 

specified magnitude of changes in a specified adverse response. For example, a BMD10 would be the 

dose at the 95% lower confidence limit on a 10% response, and the benchmark response (BMR) would be 

10%. The BMD is determined by modeling the dose response curve in the region of the dose response 

relationship where biologically observable data are feasible. 

Benchmark Dose Model—A statistical dose-response model applied to either experimental toxicological 

or epidemiological data to calculate a BMD. 

Bioconcentration Factor (BCF)—The quotient of the concentration of a chemical in aquatic organisms 

at a specific time or during a discrete time period of exposure divided by the concentration in the 

surrounding water at the same time or during the same period. 

Biomarkers—Broadly defined as indicators signaling events in biologic systems or samples. They have 

been classified as markers of exposure, markers of effect, and markers of susceptibility. 

Cancer Effect Level (CEL)—The lowest dose of chemical in a study, or group of studies, that produces 

significant increases in the incidence of cancer (or tumors) between the exposed population and its 

appropriate control. 

Carcinogen—A chemical capable of inducing cancer. 

Case-Control Study—A type of epidemiological study that examines the relationship between a 

particular outcome (disease or condition) and a variety of potential causative agents (such as toxic 

chemicals). In a case-controlled study, a group of people with a specified and well-defined outcome is 

identified and compared to a similar group of people without outcome. 

Case Report—Describes a single individual with a particular disease or exposure. These may suggest 

some potential topics for scientific research, but are not actual research studies. 
SYNTHETIC VITREOUS FIBERS 270 

10. GLOSSARY 

Case Series—Describes the experience of a small number of individuals with the same disease or 

exposure. These may suggest potential topics for scientific research, but are not actual research studies. 

Ceiling Value—A concentration of a substance that should not be exceeded, even instantaneously. 

Chronic Exposure—Exposure to a chemical for 365 days or more, as specified in the Toxicological 

Profiles. 

Cohort Study—A type of epidemiological study of a specific group or groups of people who have had a 

common insult (e.g., exposure to an agent suspected of causing disease or a common disease) and are 

followed forward from exposure to outcome. At least one exposed group is compared to one unexposed 

group. 

Cross-sectional Study—A type of epidemiological study of a group or groups of people that examines 

the relationship between exposure and outcome to a chemical or to chemicals at one point in time. 

Data Needs—Substance-specific informational needs that if met would reduce the uncertainties of human 

health assessment. 

Developmental Toxicity—The occurrence of adverse effects on the developing organism that may result 

from exposure to a chemical prior to conception (either parent), during prenatal development, or 

postnatally to the time of sexual maturation. Adverse developmental effects may be detected at any point 

in the life span of the organism. 

Dose-Response Relationship—The quantitative relationship between the amount of exposure to a 

toxicant and the incidence of the adverse effects. 

Embryotoxicity and Fetotoxicity—Any toxic effect on the conceptus as a result of prenatal exposure to 

a chemical; the distinguishing feature between the two terms is the stage of development during which the 

insult occurs. The terms, as used here, include malformations and variations, altered growth, and in utero 

death. 

Environmental Protection Agency (EPA) Health Advisory—An estimate of acceptable drinking water 

levels for a chemical substance based on health effects information. A health advisory is not a legally 

enforceable federal standard, but serves as technical guidance to assist federal, state, and local officials. 

Epidemiology—Refers to the investigation of factors that determine the frequency and distribution of 

disease or other health-related conditions within a defined human population during a specified period. 

Genotoxicity—A specific adverse effect on the genome of living cells that, upon the duplication of 

affected cells, can be expressed as a mutagenic, clastogenic, or carcinogenic event because of specific 

alteration of the molecular structure of the genome. 

Half-life—A measure of rate for the time required to eliminate one half of a quantity of a chemical from 

the body or environmental media. 

Immediately Dangerous to Life or Health (IDLH)—The maximum environmental concentration of a 

contaminant from which one could escape within 30 minutes without any escape-impairing symptoms or 

irreversible health effects. 
SYNTHETIC VITREOUS FIBERS 271 

10. GLOSSARY 

Incidence—The ratio of individuals in a population who develop a specified condition to the total 

number of individuals in that population who could have developed that condition in a specified time 

period. 

Intermediate Exposure—Exposure to a chemical for a duration of 15–364 days, as specified in the 

Toxicological Profiles. 

Immunologic Toxicity—The occurrence of adverse effects on the immune system that may result from 

exposure to environmental agents such as chemicals. 

Immunological Effects—Functional changes in the immune response. 

In Vitro—Isolated from the living organism and artificially maintained, as in a test tube. 

In Vivo—Occurring within the living organism. 

Lethal Concentration(LO) (LCLO)—The lowest concentration of a chemical in air that has been 

reported to have caused death in humans or animals. 

Lethal Concentration(50) (LC50)—A calculated concentration of a chemical in air to which exposure for 

a specific length of time is expected to cause death in 50% of a defined experimental animal population. 

Lethal Dose(LO) (LDLO)—The lowest dose of a chemical introduced by a route other than inhalation 

that has been reported to have caused death in humans or animals. 

Lethal Dose(50) (LD50)—The dose of a chemical that has been calculated to cause death in 50% of a 

defined experimental animal population. 

Lethal Time(50) (LT50)—A calculated period of time within which a specific concentration of a 

chemical is expected to cause death in 50% of a defined experimental animal population. 

Lowest-Observed-Adverse-Effect Level (LOAEL)—The lowest exposure level of chemical in a study, 

or group of studies, that produces statistically or biologically significant increases in frequency or severity 

of adverse effects between the exposed population and its appropriate control. 

Lymphoreticular Effects—Represent morphological effects involving lymphatic tissues such as the 

lymph nodes, spleen, and thymus. 

Malformations—Permanent structural changes that may adversely affect survival, development, or 

function. 

Minimal Risk Level (MRL)—An estimate of daily human exposure to a hazardous substance that is 

likely to be without an appreciable risk of adverse noncancer health effects over a specified route and 

duration of exposure. 

Modifying Factor (MF)—A value (greater than zero) that is applied to the derivation of a Minimal Risk 

Level (MRL) to reflect additional concerns about the database that are not covered by the uncertainty 

factors. The default value for a MF is 1. 
SYNTHETIC VITREOUS FIBERS 272 

10. GLOSSARY 

Morbidity—State of being diseased; morbidity rate is the incidence or prevalence of disease in a specific 

population. 

Mortality—Death; mortality rate is a measure of the number of deaths in a population during a specified 

interval of time. 

Mutagen—A substance that causes mutations. A mutation is a change in the DNA sequence of a cell’s 

DNA. Mutations can lead to birth defects, miscarriages, or cancer. 

Necropsy—The gross examination of the organs and tissues of a dead body to determine the cause of 

death or pathological conditions. 

Neurotoxicity—The occurrence of adverse effects on the nervous system following exposure to a 

chemical. 

No-Observed-Adverse-Effect Level (NOAEL)—The dose of a chemical at which there were no 

statistically or biologically significant increases in frequency or severity of adverse effects seen between 

the exposed population and its appropriate control. Effects may be produced at this dose, but they are not 

considered to be adverse. 

Octanol-Water Partition Coefficient (Kow)—The equilibrium ratio of the concentrations of a chemical 

in n-octanol and water, in dilute solution. 

Odds Ratio (OR)—A means of measuring the association between an exposure (such as toxic substances 

and a disease or condition) which represents the best estimate of relative risk (risk as a ratio of the 

incidence among subjects exposed to a particular risk factor divided by the incidence among subjects who 

were not exposed to the risk factor). An odds ratio of greater than 1 is considered to indicate greater risk 

of disease in the exposed group compared to the unexposed group. 

Organophosphate or Organophosphorus Compound—A phosphorus-containing organic compound 

and especially a pesticide that acts by inhibiting cholinesterase. 

Permissible Exposure Limit (PEL)—An Occupational Safety and Health Administration (OSHA) 

allowable exposure level in workplace air averaged over an 8-hour shift of a 40-hour workweek. 

Pesticide—General classification of chemicals specifically developed and produced for use in the control 

of agricultural and public health pests. 

Pharmacokinetics—The science of quantitatively predicting the fate (disposition) of an exogenous 

substance in an organism. Utilizing computational techniques, it provides the means of studying the 

absorption, distribution, metabolism, and excretion of chemicals by the body. 

Pharmacokinetic Model—A set of equations that can be used to describe the time course of a parent 

chemical or metabolite in an animal system. There are two types of pharmacokinetic models: data-based 

and physiologically-based. A data-based model divides the animal system into a series of compartments, 

which, in general, do not represent real, identifiable anatomic regions of the body, whereas the 

physiologically-based model compartments represent real anatomic regions of the body. 

Physiologically Based Pharmacodynamic (PBPD) Model—A type of physiologically based doseresponse model that quantitatively describes the relationship between target tissue dose and toxic end 
SYNTHETIC VITREOUS FIBERS 273 

10. GLOSSARY 

points. These models advance the importance of physiologically based models in that they clearly 

describe the biological effect (response) produced by the system following exposure to an exogenous 

substance. 

Physiologically Based Pharmacokinetic (PBPK) Model—Comprised of a series of compartments 

representing organs or tissue groups with realistic weights and blood flows. These models require a 

variety of physiological information: tissue volumes, blood flow rates to tissues, cardiac output, alveolar 

ventilation rates, and possibly membrane permeabilities. The models also utilize biochemical information 

such as air/blood partition coefficients, and metabolic parameters. PBPK models are also called 

biologically based tissue dosimetry models. 

Prevalence—The number of cases of a disease or condition in a population at one point in time. 

Prospective Study—A type of cohort study in which the pertinent observations are made on events 

occurring after the start of the study. A group is followed over time. 

q1*—The upper-bound estimate of the low-dose slope of the dose-response curve as determined by the 

multistage procedure. The q1* can be used to calculate an estimate of carcinogenic potency, the 

incremental excess cancer risk per unit of exposure (usually μg/L for water, mg/kg/day for food, and 

μg/m3

 for air). 

Recommended Exposure Limit (REL)—A National Institute for Occupational Safety and Health 

(NIOSH) time-weighted average (TWA) concentrations for up to a 10-hour workday during a 40-hour 

workweek. 

Reference Concentration (RfC)—An estimate (with uncertainty spanning perhaps an order of 

magnitude) of a continuous inhalation exposure to the human population (including sensitive subgroups) 

that is likely to be without an appreciable risk of deleterious noncancer health effects during a lifetime. 

The inhalation reference concentration is for continuous inhalation exposures and is appropriately 

expressed in units of mg/m3 or ppm. 

Reference Dose (RfD)—An estimate (with uncertainty spanning perhaps an order of magnitude) of the 

daily exposure of the human population to a potential hazard that is likely to be without risk of deleterious 

effects during a lifetime. The RfD is operationally derived from the no-observed-adverse-effect level 

(NOAEL-from animal and human studies) by a consistent application of uncertainty factors that reflect 

various types of data used to estimate RfDs and an additional modifying factor, which is based on a 

professional judgment of the entire database on the chemical. The RfDs are not applicable to 

nonthreshold effects such as cancer. 

Reportable Quantity (RQ)—The quantity of a hazardous substance that is considered reportable under 

the Comprehensive Environmental Response, Compensation, and Liability Act (CERCLA). Reportable 

quantities are (1) 1 pound or greater or (2) for selected substances, an amount established by regulation 

either under CERCLA or under Section 311 of the Clean Water Act. Quantities are measured over a 

24-hour period. 

Reproductive Toxicity—The occurrence of adverse effects on the reproductive system that may result 

from exposure to a chemical. The toxicity may be directed to the reproductive organs and/or the related 

endocrine system. The manifestation of such toxicity may be noted as alterations in sexual behavior, 

fertility, pregnancy outcomes, or modifications in other functions that are dependent on the integrity of 

this system. 
 

SYNTHETIC VITREOUS FIBERS 274 

10. GLOSSARY 

Retrospective Study—A type of cohort study based on a group of persons known to have been exposed 

at some time in the past. Data are collected from routinely recorded events, up to the time the study is 

undertaken. Retrospective studies are limited to causal factors that can be ascertained from existing 

records and/or examining survivors of the cohort. 

Risk—The possibility or chance that some adverse effect will result from a given exposure to a chemical. 

Risk Factor—An aspect of personal behavior or lifestyle, an environmental exposure, or an inborn or 

inherited characteristic that is associated with an increased occurrence of disease or other health-related 

event or condition. 

Risk Ratio—The ratio of the risk among persons with specific risk factors compared to the risk among 

persons without risk factors. A risk ratio greater than 1 indicates greater risk of disease in the exposed 

group compared to the unexposed. 

Short-Term Exposure Limit (STEL)—The American Conference of Governmental Industrial 

Hygienists (ACGIH) maximum concentration to which workers can be exposed for up to 15 minutes 

continually. No more than four excursions are allowed per day, and there must be at least 60 minutes 

between exposure periods. The daily Threshold Limit Value - Time Weighted Average (TLV-TWA) may 

not be exceeded. 

Standardized Mortality Ratio (SMR)—A ratio of the observed number of deaths and the expected 

number of deaths in a specific standard population. 

Target Organ Toxicity—This term covers a broad range of adverse effects on target organs or 

physiological systems (e.g., renal, cardiovascular) extending from those arising through a single limited 

exposure to those assumed over a lifetime of exposure to a chemical. 

Teratogen—A chemical that causes structural defects that affect the development of an organism. 

Threshold Limit Value (TLV)—An American Conference of Governmental Industrial Hygienists 

(ACGIH) concentration of a substance to which most workers can be exposed without adverse effect. 

The TLV may be expressed as a Time Weighted Average (TWA), as a Short-Term Exposure Limit 

(STEL), or as a ceiling limit (CL). 

Time-Weighted Average (TWA)—An allowable exposure concentration averaged over a normal 8-hour 

workday or 40-hour workweek. 

Toxic Dose(50) (TD50)—A calculated dose of a chemical, introduced by a route other than inhalation, 

which is expected to cause a specific toxic effect in 50% of a defined experimental animal population. 

Toxicokinetic—The study of the absorption, distribution, and elimination of toxic compounds in the 

living organism. 

Uncertainty Factor (UF)—A factor used in operationally deriving the Minimal Risk Level (MRL) or 

Reference Dose (RfD) or Reference Concentration (RfC) from experimental data. UFs are intended to 

account for (1) the variation in sensitivity among the members of the human population, (2) the 

uncertainty in extrapolating animal data to the case of human, (3) the uncertainty in extrapolating from 

data obtained in a study that is of less than lifetime exposure, and (4) the uncertainty in using lowest­
SYNTHETIC VITREOUS FIBERS 275 

10. GLOSSARY 

observed-adverse-effect level (LOAEL) data rather than no-observed-adverse-effect level (NOAEL) data. 

A default for each individual UF is 10; if complete certainty in data exists, a value of 1 can be used; 

however, a reduced UF of 3 may be used on a case-by-case basis, 3 being the approximate logarithmic 

average of 10 and 1. 

Xenobiotic—Any chemical that is foreign to the biological system. 

SYNTHETIC VITREOUS FIBERS A-1 

APPENDIX A. ATSDR MINIMAL RISK LEVELS AND WORKSHEETS 

The Comprehensive Environmental Response, Compensation, and Liability Act (CERCLA) [42 U.S.C. 

9601 et seq.], as amended by the Superfund Amendments and Reauthorization Act (SARA) [Pub. L. 99– 

499], requires that the Agency for Toxic Substances and Disease Registry (ATSDR) develop jointly with 

the U.S. Environmental Protection Agency (EPA), in order of priority, a list of hazardous substances most 

commonly found at facilities on the CERCLA National Priorities List (NPL); prepare toxicological 

profiles for each substance included on the priority list of hazardous substances; and assure the initiation 

of a research program to fill identified data needs associated with the substances. 

The toxicological profiles include an examination, summary, and interpretation of available toxicological 

information and epidemiologic evaluations of a hazardous substance. During the development of 

toxicological profiles, Minimal Risk Levels (MRLs) are derived when reliable and sufficient data exist to 

identify the target organ(s) of effect or the most sensitive health effect(s) for a specific duration for a 

given route of exposure. An MRL is an estimate of the daily human exposure to a hazardous substance 

that is likely to be without appreciable risk of adverse noncancer health effects over a specified duration 

of exposure. MRLs are based on noncancer health effects only and are not based on a consideration of 

cancer effects. These substance-specific estimates, which are intended to serve as screening levels, are 

used by ATSDR health assessors to identify contaminants and potential health effects that may be of 

concern at hazardous waste sites. It is important to note that MRLs are not intended to define clean-up or 

action levels. 

MRLs are derived for hazardous substances using the no-observed-adverse-effect level/uncertainty factor 

approach. They are below levels that might cause adverse health effects in the people most sensitive to 

such chemical-induced effects. MRLs are derived for acute (1–14 days), intermediate (15–364 days), and 

chronic (365 days and longer) durations and for the oral and inhalation routes of exposure. Currently, 

MRLs for the dermal route of exposure are not derived because ATSDR has not yet identified a method 

suitable for this route of exposure. MRLs are generally based on the most sensitive chemical-induced end 

point considered to be of relevance to humans. Serious health effects (such as irreparable damage to the 

liver or kidneys, or birth defects) are not used as a basis for establishing MRLs. Exposure to a level 

above the MRL does not mean that adverse health effects will occur. 
SYNTHETIC VITREOUS FIBERS A-2 

APPENDIX A 

MRLs are intended only to serve as a screening tool to help public health professionals decide where to 

look more closely. They may also be viewed as a mechanism to identify those hazardous waste sites that 

are not expected to cause adverse health effects. Most MRLs contain a degree of uncertainty because of 

the lack of precise toxicological information on the people who might be most sensitive (e.g., infants, 

elderly, nutritionally or immunologically compromised) to the effects of hazardous substances. ATSDR 

uses a conservative (i.e., protective) approach to address this uncertainty consistent with the public health 

principle of prevention. Although human data are preferred, MRLs often must be based on animal studies 

because relevant human studies are lacking. In the absence of evidence to the contrary, ATSDR assumes 

that humans are more sensitive to the effects of hazardous substance than animals and that certain persons 

may be particularly sensitive. Thus, the resulting MRL may be as much as 100-fold below levels that 

have been shown to be nontoxic in laboratory animals. 

Proposed MRLs undergo a rigorous review process: Health Effects/MRL Workgroup reviews within the 

Division of Toxicology, expert panel peer reviews, and agency-wide MRL Workgroup reviews, with 

participation from other federal agencies and comments from the public. They are subject to change as 

new information becomes available concomitant with updating the toxicological profiles. Thus, MRLs in 

the most recent toxicological profiles supersede previously published levels. For additional information 

regarding MRLs, please contact the Division of Toxicology, Agency for Toxic Substances and Disease 

Registry, 1600 Clifton Road NE, Mailstop F-32, Atlanta, Georgia 30333. 
 

 

SYNTHETIC VITREOUS FIBERS A-3 

APPENDIX A 

MINIMAL RISK LEVEL (MRL) WORKSHEET 

Chemical Name: Refractory Ceramic Fibers 

CAS Number: None 

Date: July 13, 2004 

Profile Status: Final Post Public Comment 

Route: [X] Inhalation [ ] Oral 

Duration: [ ] Acute [ ] Intermediate [ X ] Chronic 

Graph Key: 78 

Species: Fischer 344 Rats 

Minimal Risk Level: 0.03 [ ] mg/kg/day [ ] ppm [X] WHO fiber/cc 

References: 

Mast RW, McConnell EE, Anderson R, et al. 1995a. Studies on the chronic toxicity (inhalation) of four 

types of refractory ceramic fiber in male Fischer 344 rats. Inhal Toxicol 7:425-467. 

Mast RW, McConnell EE, Hesterberg TW, et al. 1995b. Multiple dose chronic inhalation toxicity study 

of size-separated kaolin refractory ceramic fiber in male Fischer 344 rats. Inhal Toxicol 7(4):469-502. 

Bernstein DW, Sintes JMR, Ersboell BK, et al. 2001b. Biopersistence of synthetic mineral fibers as a 

predictor of chronic inhalation toxicity in rats. Inhal Toxicol 13:823-849. 

Maxim LD, Yu CP, Oberdörster G, et al. 2003. Quantitative risk analyses for RCF: survey and 

synthesis. Regul Toxicol Pharmacol 38:400-416. 

Experimental design and effects noted: 

In the multiple-exposure level study (Mast et al. 1995b), four groups of about 140 male F344 rats were 

exposed via nose-only inhalation to 0 (filtered air controls), 3, 9, or 16 mg/m3

 of a refractory ceramic 

fiber called RCF1, 6 hours/day, 5 days/week for up to 24 months. The companion study (Mast et al. 

1995a) exposed two groups of about 140 male F344 rats to 0 or 30 mg/m3

 RCF1 (from the same lot as the 

multiple-exposure level study) via the same protocol. 

The RCF1 test material was prepared from a bulk sample of kaolin-based refractory ceramic fiber 

obtained from Carborundum Company, Niagara Falls, New York. The bulk material was separated 

(before aerosol generation) to concentrate the numbers of fibers with a targeted nominal arithmetic mean 

diameter of 1 μm and length of 20–30 μm. These dimensions were chosen based on results of an 

unpublished simulated workplace exposure study showing airborne fibers to be principally of this size 

range. The generated aerosols had the characteristics listed in Table A-1. In addition to fibers (i.e., 

particles with length:diameter ≥3:1), the aerosols contained nonfibrous particles, often referred to as 

“shot”. In the experimental aerosols, the ratios of nonfibrous particles (with diameters <3 μm) to total 

fibers or to WHO fibers were reported by Mast et al. (1995b) to range from 0.9 to 1.5 or from 1.3 to 1.96, 

respectively (Table A-1). 
 

SYNTHETIC VITREOUS FIBERS A-4 

APPENDIX A 

Table A-1. RCF1 Aerosol Characteristics in the 2-Year Inhalation Bioassays with 

F344 Rats (Mast et al. 1995a, 1995b) 

Character (mean [± standard deviation]) 3 mg/m3 9 mg/m3 16 mg/m3 30 mg/m3 

Gravimetric concentration (mg/m3) 3.0±0.4 8.8 ±0.7 16.5±1.1 29.1±5.2 

Total fibers/cc (L:D≥3) 36±17 91±34 162±37 234±35 

WHO fibers/cc (L>5 μm; D<3 μm; L:D≥3) 26±12 75±35 120±35 187±53 

Diameter (D) range (μm) 0.08–5.32 0.08–5.37 0.07–4.83 0.12–4.53 

Length (L) range (μm) 0.77–93.93 1.09–98.25 1.24–97.88 1.30–76.6 

Arithmetic mean D (μm) 1.02±0.73 1.02±0.71 1.02±1.70 0.98±0.61 

Geometric mean D (μm) 0.80±2.06 0.80±2.03 0.82±1.99 0.82±1.89 

Arithmetic mean L (μm) 20.2±18.10 20.3±17.1 19.6±16.5 22.3±17.0 

Geometric mean L (μm) 13.5±2.60 13.9±2.50 13.8±2.4 15.9±2.4 

Nonfibrous particle counts 

≤1 μm/cc 28.3±19.3 85.7± 63.2 88.0±52.4 17±154 

1–3 μm/cc 23.0±11.8 54.8±38.4 68.4±24.2 135±45 

3 μm/cc 17.1±8.4 43.6±25.2 58.6±27.1 81±29 

Ratio nonfibrous particles (<3 μm):total fibers 1.41 1.54 0.97 1.31 

Ratio nonfibrous particles (<3 μm):WHO fibers 1.96 1.87 1.30 1.63 

Groups of 3–6 rats from each exposure group were killed at 3, 6, 12, 18, and 24 months of exposure. 

Additional groups of 3–6 rats were removed from exposure at 3, 6, 12, and 18 months and exposed to 

filtered air until they were sacrificed at 24 months. Remaining rats exposed for 24 months (15–32 rats per 

group) were held without further exposure until 30 months when survivors were killed. All rats were 

necropsied. Lung tissues were removed, and weighed, and the left lung was prepared for routine 

histopathology that included staining for collagen deposition. Other tissues processed for histopathology 

included the nasal cavity, larynx, trachea, bronchi, mediastinal and mesenteric lymph nodes, liver, spleen, 

kidneys, heart, and all tissues with grossly visible lesions. The concentration and size distributions of 

fibers in lung tissue were determined after ashing of accessory lung lobes. All fibers detected in lungs 

had diameters <3 μm. Concentrations were expressed as total fibers per mg dry lung (length:diameter >3) 

or WHO fibers per mg dry lung (length >5 μm, diameter <3 μm, and length:diameter ≥3). 

Observed nonneoplastic lung lesions were classified with two different grading scales. One scale (the 

Wagner scale) contained eight grades ranging from a normal grade of 1 (with no lesions observed), 

through “cellular change” grades 2 and 3 (few to conspicuous macrophages in terminal bronchioles and 

alveoli and no collagen deposition at the bronchiolo-alveolar junction), to five “fibrosis” grades. The 

fibrosis grades increased in severity as follows: grade 4 (minimal), minimal collagen deposition at the 

bronchoalveolar junction, increased bronchiolization, and associated mucoid debris; grade 5 (mild), 

interlobular linking of collagen deposition; grade 6 (moderate), early consolidation and decrease in 

parenchyma tissue; grade 7 (severe), marked fibrosis and consolidation; and grade 8, complete 

obstruction of most airways. The other scale contained five grades (0=normal; 1=minimal; 2=mild; 

3=moderate; 4=marked; 5=severe) and was applied to specific histopathological findings (macrophage 

aggregation, bronchiolization, granuloma presence, interstitial [i.e., pulmonary] fibrosis, and pleural 

fibrosis). 

Survival was not statistically significantly affected in any of the exposed groups compared with controls. 

Body weights and body weight gains were not affected in the two lowest exposure groups (3 and 
 

 

SYNTHETIC VITREOUS FIBERS A-5 

APPENDIX A 

9 mg/m3). At sporadic intervals of exposure, rats exposed to 16 or 30 mg/m3 displayed statistically 

significant decreases in body weight, compared with controls. The decreases were not >10% of control 

values, and are not considered an adverse effect. In 16- and 30-mg/m3

 rats, absolute and relative lung 

weights were significantly greater than in control rats, as early as after 3 months of exposure. After 

24 months of exposure, mean absolute lung weights in these groups were respectively increased by 

32 and 65%, compared with controls. The lung weight changes are considered to be an indicator of 

pulmonary inflammation from repeated exposure to RCF1. 

Lung fiber concentrations increased with increasing exposure duration and concentration. At 24 months, 

mean values of WHO fibers/mg lung were 4.29x104

, 15.60x104, 22.10x104, and 27.50x104 for the 3-, 9-, 

16-, and 30-mg/m3

 groups, respectively. Mean values for total fibers/mg lung were 5.55±1.71, 

18.80±3.59, 27.80±6.06, and 37.00±8.01, respectively. 

Exposure-related nonneoplastic histopathological lesions were restricted to the lung or pleura. Signs of 

pulmonary inflammation (macrophage aggregation, bronchiolization, and granuloma presence) were 

observed in all exposed groups after 3 months of exposure, whereas these lesions did not occur in the 

control rats at any interval (see Table A-2). At 24 months, mean scores (on the five-grade scale) in the 

3- and 30-mg/m3

 groups ranged from 2 to 3.2 for macrophage aggregation, from 1.2 to 2.7 for 

bronchiolization, and from 1.5 to 2 for granuloma presence (Table A-2). The mean scores reflect 

progression of the severity of the inflammatory lesions with increasing exposure concentration 

(Table A-2). There is also some evidence of progression of the severity of the inflammatory lesions with 

increasing duration of exposure, most notably between 3 and 12 months (Table A-2). 

Signs of interstitial (i.e., pulmonary) fibrosis and pleural fibrosis appeared in rats exposed to 

concentrations ≥9 mg/m3

 (Table A-2). The five-grade scores for interstitial fibrosis and pleural fibrosis 

(see note about these scores below) showed some progression in severity with exposure duration and 

concentrations, but the average severity scores for the exposed groups did not progress beyond a score of 

3 (moderate) for pulmonary fibrosis or a score of 2 (mild) for pleural fibrosis (Table A-2). Signs of 

fibrosis did not appear until 12 months of exposure. Using the eight-grade Wagner scale to classify the 

pulmonary cellular changes and fibrosis, the mean scores at 24 months were 1.0 (normal), 3.2, 4.0, 4.2, 

and 4.0 for the control, 3-, 9-, 16-, and 30-mg/m3

 groups, respectively. In rats exposed for 24 months and 

allowed to live without exposure to 30 months, respective mean scores were 1.0, 2.9, 3.8, 4.0, and 4.3 

(Table A-2). These scores indicate that the pulmonary lesions produced by 24 months of exposure 

showed only minor, if any, regression and that, on average, the most severe nonneoplastic lesions formed 

were classified as minimal to mild fibrosis. It was reported that the principal difference between 

24-month exposed rats killed at 24 and 30 months was a reduction in the number of pulmonary 

macrophages and granulomas in the 30-month rats; pulmonary or pleural fibrosis showed no signs of 

regression. 

In a later published report, Bernstein et al. (2001b) reported that the pathologist, who originally scored the 

histological slides from the RCF1 2-year bioassay, had provided scores for collagen deposition at the 

bronchoalveolar junction. This lesion was scored in each rat on a five-scale system as follows:

 0=normal; 

1=minimal–very few (1 or 2 foci) and very small foci of collagen deposition of insufficient 

severity to score as Grade 4 in the eight-grade Wagner scale; 

2=mild–slight, but easily detected, few, small foci of collagen deposition, minimally sufficient 

to classify in Grade 4 of the Wagner scale; 

3=moderate–easily detected foci of collagen deposition in considerably enlarged areas, 

corresponding to Grade 4 of the Wagner scale; 
 

 

 

SYNTHETIC VITREOUS FIBERS A-6 

APPENDIX A 

4=marked–marked, obvious, or extensive foci of collagen deposition extending into the 

interstitium, and corresponding to Grade 4 of the Wagner scale; 

5=severe–widespread collagen deposition with consolidation at the bronchoalveolar junction, 

sometimes with interlobular linking, corresponding to Grade 4 to 5 of the Wagner scale. 

In accordance with this scale, collagen deposition at the bronchoalveolar junction is taken as an early 

response at the site where fibrosis can develop. The lesion is not classified as pulmonary fibrosis at a 

minimal score of 1, but is classified as minimal to mild fibrosis at scores of 2–5. The mean scores 

(±standard deviations) for the collagen deposition scores reported by Bernstein et al. (2001b) for the six 

rats in each of the groups sacrificed at 24 months were: control (n=12), 0 (normal); 3 mg/m3

, 0.67±0.8; 

9 mg/m3

, 2.0±0; 16 mg/m3, 2.83±0.4; and 30 mg/m3, 2.17±0.4. These mean scores for collagen 

deposition are identical to the mean scores for the lesion named “pulmonary fibrosis” in the Mast et al. 

(1995a, 1995b) report and shown in Table A-2. Thus, the scores for “pulmonary fibrosis” shown in 

Table A-2 are actually for collagen deposition as per the original pathology reports. 

Neoplastic lesions (lung adenomas, lung carcinomas, and mesotheliomas) were found most prominently 

in rats exposed to 30 mg/m3

. The tumors appeared predominately late in life. The first adenoma occurred 

in rats sacrificed at 18 months; carcinomas and mesotheliomas were detected only in the 30-monthsacrifice animals. Incidences for rats (that survived to 12 months) with bronchoalveolar hyperplasia were 

8/129, 10/123, 16/127, 13/124, and 17/123 for the control through high-exposure groups. Combined 

incidences for lung adenomas or carcinoma were 1/129, 2/123, 5/127, 2/124, and 16/123. Incidences for 

mesothelioma were 0/129, 0/123, 1/127, 0/124, and 2/123. Incidences for mesothelial proliferation were 

1/129, 0/123, 1/127, 1/124, and 9/123. 

Table A-2. Mean Severity Scores for Pulmonary Lesions in F344 Rats Exposed to 

RCF1 (Mast et al. 1995a, 1995b)a 

Exposure Pleural 

level/ Macrophage Bronchio- Pulmonary fibrosis 8-Grade 

sacrifice Number Aggregation lization (0– Granuloma fibrosis (0– (0– Wagner 

month of rats (0–5 scale) 5 scale) (0–5 scale) 5 scale) 5 scale) scale score 

Control 

3 3 0 0 0 0 0 1.0 

6 3 0 0 0 0 0 1.0 

12 6 0 0 0 0 0.3 1.0 

18 6 0 0 0 0 0 1.0 

24 6 0 0 0 0 0 1.0 

30b

 32 0.1 0.1 0 0 0 1.0 

3 mg/m3 

3 3 1.7 0 0.7 0 0 2.0 

6 3 1.7 0 1 0 0 2.0 

12 6 2 1 1.3 0.2 0 3.0 

18 6 2 1.2 1.7 0.7 0.7 3.2 

24 6 2 1.2 1.5 0.7 0.5 3.2 

30b 23 2.4 1.7 1.5 0.8 0.5 2.9 

9 mg/m3 

3 3 2 0.3 1.3 0 0 2.3 

6 3 2 0.7 2 0 0.3 2.7 

12 6 2.3 1.2 2.2 1.7 0.2 4.0 
 

 

SYNTHETIC VITREOUS FIBERS A-7 

APPENDIX A 

Table A-2. Mean Severity Scores for Pulmonary Lesions in F344 Rats Exposed to 

RCF1 (Mast et al. 1995a, 1995b)a 

Exposure Pleural 

level/ Macrophage Bronchio- Pulmonary fibrosis 8-Grade 

sacrifice Number Aggregation lization (0– Granuloma fibrosis (0– (0– Wagner 

month of rats (0–5 scale) 5 scale) (0–5 scale) 5 scale) 5 scale) scale score 

18 6 2.3 1.8 2.2 1.8 0.7 4.0 

24 6 2.5 1.8 2.2 2 0 4.0 

30b 25 2.7 1.7 1.7 1.7 0.5 3.8 

16 mg/m3 

3 3 2 1 2 0 0 3.0 

6 3 2.3 1.3 2 0 0 3.0 

12 6 3 1.8 2.8 2.8 0.7 4.0 

18 6 3 2.7 2.7 2.2 1.2 4.0 

24 6 3 2.7 2.7 2.8 1.5 4.2 

30b

 20 3 2.5 2.1 2 1 4.0 

30 mg/m3 

3 3 2 1 2 2 0 3.3 

6 3 2.7 2 2 2 0 4.0 

12 6 3 2.3 2.5 2.5 1.5 4.0 

18 3 3 2 2.3 2.3 1 4.3 

24 6 3.2 2.7 2 2 0.5 4.0 

30b 15 2.8 2.9 1.9 1.9 1.3 4.3 a

0–5 Scale for different types of lesions: 0=normal; 1=minimal; 2=mild; 3=moderate; 4=marked: 5=severe. 8-Grade 

Wagner Scale for pulmonary cellular change and fibrosis: 1=normal; 2 or 3=cellular change consistent with 

inflammation; 4=minimal fibrosis with collagen deposition, bronchiolization, and mucoid debris; 5=mild fibrosis with 

some interlobular linking of collagen; 6=moderate fibrosis with consolidation and parenchymal decrease; 7=severe 

fibrosis and consolidation; 8=complete obstruction of airways. 

b

Exposed for 24 months and sacrificed at 30 months. 

c

Bernstein et al. (2001b) reported that the original pathologist’s score for this lesion was for collagen deposition at 

the bronchoalveolar junction, not for pulmonary fibrosis; in the five-grade scale used for collagen deposition, a 

minimal score of 1 is of insufficient severity to be classified as minimal fibrosis (Grade 4 on the Wagner scale). 

Dose and end point used for MRL derivation: 

Benchmark concentration analysis was conducted for lung weights (absolute weight expressed as percent 

of control), macrophage aggregation scores, bronchiolization scores, and scores for collagen deposition at 

the bronchoalveolar junction. Changes in the first three variables are taken as signs of pulmonary 

inflammation induced by refractory ceramic fibers deposited in the lung. ATSDR policy considers 

pulmonary fibrosis to be a serious adverse effect that is inappropriate for MRL derivation. Scores for 

collagen deposition at the bronchoalveolar junction were included in the analysis, because a score of 1 for 

this lesion is not of sufficient severity to be considered fibrosis; only scores ≥2 were classified as 

pulmonary fibrosis. 

Continuous-variable models available in the EPA Benchmark Dose Software were fit to the lung weight, 

macrophage, bronchiolization, and bronchoalveolar collagen deposition data shown in Table A-3. Each 

of these end points was increasingly affected with increasing exposure level and increasing concentrations 

of fibers in the lungs at 24 months (Table A-3). Group means and standard deviations of the lung weight, 

macrophage aggregation scores, and bronchiolization scores were obtained from a report of an analysis of 
 

 

SYNTHETIC VITREOUS FIBERS A-8 

APPENDIX A 

the Mast et al. (1995a, 1995b) 24-month-sacrifice data by Yu and Oberdörster (2000). The mean scores 

and standard deviations for collagen deposition at the bronchoalveolar junction were obtained from data 

in the report by Bernstein et al. (2001b). The published report by Mast et al. (1995a, 1995b) only cited 

mean values and did not cite standard deviations. Dr. Yu’s analysis did not include scores (and standard 

deviations) for granuloma presence. 

The benchmark response level for lung weight was set at 10% increase in weight. Percentage change 

below this value is assumed to be nonadverse. Benchmark response levels for scores for macrophage 

aggregation, bronchiolization, and bronchoalveolar collagen deposition were set at 1.0 (minimal rating on 

the 0–5 scale, where 0=normal). 

Table A-3. Non-neoplastic Lung Responses in F344 Rats Exposed for 24 Months 

to RCF1 (Mast et al. 1995a, 1995b) 

Exposure Fiber concentrations Lung 

level in lungs at 24 months weight Mean score±standard deviation (0–5 Scale) 

(total 

fibers/cc) 

(mean total fibers per 

mg lung x104

) 

(Percent of 

control) 

Macrophage 

aggregation 

Bronchiolization Collagen deposition at the 

bronchoalveolar junction 

0 (n=12) NR 100.0±14.0 0±0 0±0 0±0 

36 (n=6) 5.55±1.71 116.8±12.3 2.0±0 1.2±0.4 0.7±0.82 

91 (n=6) 18.80±3.59 110.9±8.1 2.5±0.6 1.8±0.4 2±0 

162 (n=6) 27.80±6.06 131.8±15.3 3.0±0 2.7±0.5 2.8±0.4 

234 (n=6) 37.00±8.01 164.7±44.2 3.2±0.4 2.7±0.5 2.2±0.4 

0–5 Scale: 0=normal; 1=minimal; 2=mild; 3=moderate; 4=marked; 5=severe; NR= not reported 

[ ] NOAEL [ ] LOAEL [X] Benchmark Concentration: Lower 95% confidence limits on benchmark 

concentrations (BMCLs = lower 95% confidence limit on the estimated concentrations associated with a 

mean score of 1.0 for macrophage aggregation, bronchiolization, or collagen deposition, or 10% increase 

in lung weight) were considered for selection of the point of departure for the MRL. The rat exposureresponse data for these four end points were first fit to continuous-variable models. The best-fitting 

models were then used to calculate rat BMCLs for each of the end points. The point of departure for the 

MRL was selected from the rat BMCLs. The selected rat BMCL was then converted to a BMCLHEC using 

a cross-species scaling factor derived from the lung deposition and clearance models developed for RCF1 

in rats and humans (Maxim et al. 2003b; Yu and Oberdörster 2000; Yu et al. 1995a, 1995b, 1996, 1997, 

1998a, 1998b). 

Benchmark Concentration Modeling Results. Available continuous-variable models in the EPA 

Benchmark Dose Software (linear, polynomial, power, and Hill models; BMDS version) were fit to the 

data shown in Table A-3. 

Lung Weight. Adequate fits to the data (as assessed by chi-square residuals and log-likelihood ratio fit 

tests in the BMDS) were obtained with the linear, polynomial, power, and Hill models with constant 

variance assumed. Statistical tests indicated that variances were not constant across exposure groups (this 

is reflected in the standard deviations listed in Table A-3). Models with non-homogeneous variance (i.e., 

variance as a power function of dose) generally provided improved fits to the data as assessed with 

Aikake’s Information Criteria, AIC (Table A-4). Comparing across models, a better fit is indicated by a 

lower AIC. The best-fitting model, as indicated by the AIC, was the power model with non-homo­
 

SYNTHETIC VITREOUS FIBERS A-9 

APPENDIX A 

geneous variance, which predicted a rat BMC and BMCL of 133 and 79 total fibers/cc, respectively 

(Figure A-1). 

Table A-4. BMC Modeling Results for Lung Weights in Rats Exposed to RCF1 for 

24 Months (Mast et al. 1995a, 1995b) 

Model BMC (total fibers/cc) BMCL (total fibers/cc) AIC-fitted 

Linear 40 30 220.12 

Linear-nonhomogeneous .9 32 213.51 

Polynomial 95 34 220.08 

Polynomial-nonhomogeneous 94 43 211.52 

Power 110 35 222.00 

Power-nonhomogeneous* 133* 79* 209.30* 

Hill 10 35 224.00 

Hill-nonhomogeneous 60 6 228.90 

*Best Fitting Model 

Figure A-1. Predicted (Power Model with Nonhomogeneous Variance) and Observed 

Lung Weights in Rats Exposed to RCF1 for 24 Months (Mast et al. 1995a, 1995b) 

(Dose Refers To Rat Exposure Concentrations, Total Fibers/cc) 

Power Model with 0.95 Confidence Level 

220 

200 

Mean Response 180 

160 

140 

120 

100 

80 BMDL BMD 

Power 

0 50 100 150 200 250 

dose 

09:37 02/13 2004 

Macrophage Aggregation Scores. Adequate fits to the data (as assessed by chi-square residuals and loglikelihood fit tests in the BMDS) were obtained with the polynomial, power, and Hill models with 

constant variance assumed. Models with variance as a power function of dose did not improve the fits to 

the data. As assessed by AIC (Table A-5), the Hill model provided the best fit to the data, yielding a rat 

BMC and BMCL of 12 and 9 total fibers/cc, respectively (Figure A-2). 
 

 

SYNTHETIC VITREOUS FIBERS A-10 

APPENDIX A 

Table A-5. BMC Modeling Results for Scores for Pulmonary Macrophage Aggregation in 

Rats Exposed to RCF1 for 24 Months (Mast et al. 1995a, 1995b) 

Model BMC (total fibers/cc) BMCL (total fibers/cc) AIC-fitted 

Hill* 12* 9* -33.05* 

Polynomial 21 13 -12.08 

Polynomial-nonhomogeneous 13 0 -8.44 

Power 6 0 13.67 

Power-nonhomogeneous 51 0 15.02 

*Best Fitting Model 

Figure A-2. Predicted (Polynomial Model with Constant Variance) and Observed Scores 

for Pulmonary Macrophage Aggregation in Rats Exposed to RCF1 for 24 Months (Mast 

et al. 1995a, 1995b) (Dose Refers to Rat Exposure Concentrations, Total Fibers/cc) 

Hill Model with 0.95 Confidence Level 

0 

0.5 

1 

1.5 

2 

2.5 

3 

3.5 

Mean Response 

BMDL BMD 

Hill 

0 50 100 150 200 250 

dose 

09:56 02/13 2004 

Bronchiolization Scores. Adequate fits to the data (as assessed by chi-square residuals and log-likelihood 

fit tests in the BMDS) were obtained with the polynomial and Hill models with constant variance 

assumed. Benchmark concentration calculations failed when models with variance as a power function of 

dose were fit to the data. The best-fitting model, as assessed by AIC, was the polynomial (2-degree) 

model (Table A-6), which yielded a rat BMC and BMCL of 37 and 30 total fibers/cc, respectively 

(Figure A-3). 
 

 

SYNTHETIC VITREOUS FIBERS A-11 

APPENDIX A 

Table A-6. BMC Modeling Results for Scores for Bronchiolization in Rats Exposed to 

RCF1 for 24 Months (Mast et al. 1995a 1995b) 

Model BMC (total fibers/cc) BMCL (total fibers/cc) AIC-fitted 

Polynomial* 37* 30* -19.91* 

Hill 30 22 -18.28 

*Best Fitting Model 

Figure A-3. Predicted (Polynomial Model with Constant Variance) and Observed Scores 

for Bronchiolization in Rats Exposed to RCF1 for 24 Months (Mast et al. 1995a, 1995b) 

(Dose Refers to Rat Exposure Concentrations, Total Fibers/cc) 

Polynomial Model with 0.95 Confidence Level 

0 

0.5 

1 

1.5 

2 

2.5 

3 

3.5 

Mean Response 

BMDL BMD 

Polynomial 

0 50 100 150 200 250 

dose 

10:44 02/13 2004 

Collagen Deposition Scores. Adequate fits to the data (as assessed by chi-square residuals and loglikelihood ratio fit tests in the BMDS) were obtained with the polynomial and Hill models with constant 

variance assumed. Benchmark concentration calculations failed when models with variance as a power 

function of dose were fit to the data. The best-fitting model, as assessed by AIC, was the polynomial 

(2-degree) model (Table A-7), which yielded a rat BMC and BMCL of 37 and 32 total fibers/cc, 

respectively (Figure A-4). 
 

SYNTHETIC VITREOUS FIBERS A-12 

APPENDIX A 

Table A-7. BMC Modeling Results for Scores for Collagen Deposition at the 

Bronchoalveolar Junction in Rats Exposed to RCF1 for 24 Months 

(Mast et al. 1995a, 1995b) 

Model BMC (total fibers/cc) BMCL (total fibers/cc) AIC-fitted 

Polynomial* 37* 32* -12.52* 

Hill 45 37 -5.25 

*Best Fitting Model 

Figure A-4. Predicted (Polynomial Model with Constant Variance) and Observed Scores 

for Collagen Deposition at the Bronchoalveolar Junction in Rats Exposed to RCF1 for 

24 Months (Mast et al. 1995a, 1995b) (Dose Refers to Rat Exposure Concentrations, 

Total Fibers/cc) 

Polynomial Model with 0.95 Confidence Level 

0 50 100 150 200 250 

dose 

11:26 02/13 2004 

Selection of Point of Departure for the MRL. BMCs and BMCLs for the four modeled end points are 

shown in Table A-8. The BMCL for lung weight represents the 95% lower confidence limit on the 

concentration estimated to increase lung weight by a mean of 10% over control values. The BMCLs for 

the pulmonary lesion scores represent the 95% lower confidence limits on the concentration estimated to 

produce a mean score of 1 (minimal severity) for each lesion. 

-0.5 

0 

0.5 

1 

1.5 

2 

2.5 

3 

3.5 

Mean Response 

BMDL BMD 

Polynomial 
SYNTHETIC VITREOUS FIBERS A-13 

APPENDIX A 

Table A-8. BMCs and BMCLs for Lung Weight and Pulmonary Lesion Scores in 

Rats Exposed to RCF1 for 24 Months (Mast et al. 1995a, 1995b). 

End point BMC (total fiber/cc) BMCL (total fiber/cc) 

Lung weight 133 79 

Pulmonary macrophage aggregation 12 9 

Bronchiolization 37 30 

Collagen deposition at the bronchoalveolar junction 37 32 

The rat BMCL of 9 total fiber/cc for pulmonary macrophage aggregation was selected as the point of 

departure for the MRL, because this lesion is the most sensitive among those measured in the bioassay (as 

indicated by having the lowest BMCL in Table A-8). ATSDR considers minimal pulmonary 

inflammation a reversible response to fibers and nonfibrous particles that, although near the boundary 

between adverse and nonadverse, is an appropriate critical effect on which to base the MRL. As shown in 

the data in Table A-3, the severity of pulmonary macrophage aggregation in rats in the principal study 

showed a clear increase in severity with increasing exposure levels of RCF1, as well as with increasing 

concentrations of fibers in the lungs of the rats sacrificed after 24 months of exposure. 

Dosimetric Adjustment of Rat Benchmark Concentrations to Human Equivalent Concentrations (HECs) 

The BMC and BMCL for pulmonary aggregation in rats were converted to human equivalent exposure 

levels using an average scaling factor derived from rat and human lung deposition and clearance models 

for RCF1 developed by Dr. C.P. Yu and colleagues (Yu et al. 1995a, 1995b, 1996, 1997, 1998a, 1998b). 

Equations for deposition in the models are functions of fiber length, fiber diameter, and time. The 

equations for mechanical macrophage-mediated clearance rate are functions of fiber length, alveolar 

macrophage volume, and lung burden (total accumulated volume of fibers and particles). The clearance 

models include dissolution-rate and transverse breakage-rate equations. 

Values for key parameters in the dosimetric models included the following (Maxim et al. 2003b;Yu and 

Oberdörster 2000): 

Rat lung weight: 1.48 g; Human lung weight: 1,000 g 

Rat lung surface area: 4.3x103

 cm2; Human lung surface area: 6.5x105 cm2 

Rat macrophage volume per lung: 26 mm3

; Human macrophage volume per lung: 1.75x104 mm3 

Rat macrophage diameter: 10.68 μm; Human macrophage diameter: 16.82 μm 

Dissolution rate (same in rats and humans): 6.46x10-5 (μm/day) or 0.73 ng/cm2

/hour 

Breakage rate and scheme: same in rats and humans 

Size distribution of refractory ceramic fibers in the human model: 

Bivariate lognormal distribution (geometric mean±standard deviation) similar to workplace RCF 

size data: fiber diameter: 0.84 μm (±2.05); fiber length: 14.1 μm (±2.48) 

Rat model: retained volume of nonfibrous plus fibrous particles (lung burden) impacts clearance 

rate 

Human model: only retained fibrous particle volume impacts clearance rate. 

Initially, Yu and Oberdörster (2000) calculated HECs from the rat exposure levels, using number of 

WHO fibers per cm2 of lung surface area as the cross species lung burden normalization unit. The rat 

models were set to the exposure scenarios experienced by rats in the Mast et al. (1995a, 1995b) bioassays 

(6 hours/day, 5 days/week for 2 years), and two human exposure scenarios were examined, one involving 

continuous, lifetime (70-year) exposure assuming a tidal volume of 750 cc and nasal breathing with a 

respiratory frequency of 14.5 per minute, and a second involving occupational exposure (8 hours/day, 
 

SYNTHETIC VITREOUS FIBERS A-14 

APPENDIX A 

5 days/week, 50 weeks/year for 40 years) assuming a tidal volume of 1290 cc and nasal breathing with a 

respiratory frequency of 15.5 per minute. Calculated HECs for the two human exposure scenarios from 

the rat exposure levels are shown in Table A-9. The mean ratios of the rat:human equivalent exposure 

concentrations were 14.7 for the continuous exposure scenario and 7.3 for the occupational exposure 

scenario. From these ratios, mean rat-to-human dosimetric scaling factors are 0.07 (1/14.7) for the 

continuous exposure scenario and 0.13 (1/7.3) for the occupational exposure scenario. 

Table A-9. HECs Calculated for Two Human Exposure Scenarios from Rat Exposure 

Levels Using WHO Fibers per cm2 of Lung Surface area for Cross-Species Normalization. 

(Source: Tables 7.1 and 7.2; Yu and Oberdörster, 2000) 

Human exposure scenario Rat exposure levels (total fibers/cc) Mean ratio 

0 36 91 162 234 rat:human (±SD) 

HECs (WHO fibers/cc) 

Continuous 0 2.4 8.1 11.0 13.2 14.7 ±2.7 

Occupational 0 4.7 16.2 22.3 27.1 7.3 ±1.3 

More recently, Maxim et al. (2003) showed that selection of the cross species lung burden normalization 

unit (i.e., number of fibers per cm2 of lung surface area versus number of fibers per mg dry weight of 

lung) is a key determinant in species conversion of exposure levels when using the lung and deposition 

models developed by Yu and colleagues. Using a human occupational exposure scenario assuming a tidal 

volume of 1,060 cc and nasal breathing with a respiratory frequency of 12.74 per minute and a minute 

ventilation of 13.5 L per minute, human equivalent concentrations corresponding to a rat exposure level 

of 36 total fiber/cc were calculated to be 5.7 total fiber/cc, based on a WHO fibers per cm2

 of lung surface 

area normalization, compared with 33.8 total fibers/cc, based on a WHO fibers per lung mg dry weight 

normalization. The ratios of rat:human equivalent exposure concentrations for these occupational 

exposure scenarios were 6.3 on a lung surface area basis (similar to the mean of 7.3 shown in Table A-9) 

and 1.1 on a lung dry weight basis. For this occupational exposure scenario, rat-to-human dosimetric 

scaling factors based on lung surface area normalization or lung dry weight normalization are 0.16 (i.e., 

1/6.3) and 0.9 (1/1.1), respectively, indicating an approximate 6-fold difference between lung surface area 

and lung dry weight normalizations. 

A rat-to-human scaling factor of 0.07, based on a human continuous exposure scenario and lung surface 

area cross-species normalization, was used to convert the rat BMC and BMCL of 12 and 9 total fibers/cc 

to human equivalent concentrations of 0.8 and 0.6 WHO fibers/cc, respectively. This scaling factor was 

used, because data are not available to confirm which cross-species lung burden normalization method is 

more accurate, and calculations of mean rat-to-human dosimetric scaling factors, based on lung dry 

weight normalization with continuous exposure scenarios, are not available. It is recognized that the 

analysis by Maxim et al. (2003) indicates that an alternative scaling factor, based on lung dry weight cross 

species normalization, could be about 6-fold higher. The point of departure for the MRL is the 

BMCLHEC of 0.6 WHO fibers/cc, rounded to 1 WHO fibers/cc. 

Uncertainty Factors used in MRL derivation: 

[X] 3 for interspecies extrapolation with dosimetric adjustment. The dosimetric adjustment takes into 

account physiological differences between rats and humans expected to influence deposition and 

clearance of refractory ceramic fibers from the lung. It is recognized that the cross species dosimetric 

scaling factor used (based on fiber per lung surface area normalization) may underestimate the human 

equivalent concentration associated with the development of pulmonary lesions, compared with a scaling 

factor based on a fiber per lung dry weight basis. As such, the scaling factor based on lung surface area 
SYNTHETIC VITREOUS FIBERS A-15 

APPENDIX A 

normalization is likely to be protective of the public health, and an additional factor to account for this 

dosimetric uncertainty is unnecessary. The derivation assumes that rats and humans are equally 

responsive to retained fibers in the lung, in the absence of conclusive evidence to indicate otherwise. The 

uncertainty factor of 3 accounts for the uncertainty associated with this assumption of interspecies 

pharmacodynamic equivalence. 

[ ] 10 for use of a LOAEL: No uncertainty factor was necessary for the use of a BMCLHEC for minimal 

pulmonary macrophage aggregation, an effect just above the boundary between nonadverse and adverse. 

[ X ] 10 for human variability 

Was a conversion used from ppm in food or water to a mg/body weight dose? No. 

Was a conversion used from intermittent to continuous exposure? Yes. The human lung and deposition 

model used a continuous, 70-year, exposure scenario, whereas the rat lung and deposition model used the 

experimental exposure conditions, 6 hours/day, 5 days/week for 2 years. 

If an inhalation study in animals, list conversion factors used in determining human equivalent dose: See 

previous discussion of the derivation of the rat-to-human dosimetric scaling factor of 0.07. 

Other additional studies or pertinent information which lend support to this MRL: The Mast et al. (1995a, 

1995b) study provides the best available data describing exposure-response relationships for 

nonneoplastic lesions in the lung and pleura from chronic inhalation exposure to refractory ceramic fibers. 

The study identifies pulmonary inflammation as the critical nonneoplastic end point of concern and 

identifies other more serious effects at higher exposure levels (pulmonary and pleural fibrosis and cancer 

of the lung and pleura). Other studies of rats exposed to RCF1 by inhalation provide strong support for 

pulmonary inflammation as the critical end point (Bellman et al. 2001; Everitt et al. 1997; Gelzleichter et 

al. 1999; McConnell et al. 1995), as well as other animal inhalation studies of other refractory ceramic 

fibers (Mast et al. 1995a) and other synthetic vitreous fibers such as insulation glass wools, MMVF10 and 

MMVF11 (Hesterberg et al.1993c; McConnell et al. 1999), slag wool MMVF22 (McConnell et al. 1994), 

and rock wool MMVF21 (McConnell et al. 1994). 

There are distinct differences between laboratory animal species and humans in respiratory tract size and 

geometry, ventilation rate and pattern, and macrophage sizes that influence the retention (the net result of 

deposition and clearance) of fibers in the lung. Yu and colleagues (Yu et al. 1995a, 1995b, 1996, 1997, 

1998a, 1998b) have developed lung retention models for RCF1 in rats and humans that incorporate many 

of these interspecies differences. Although these models significantly decrease uncertainty in 

extrapolating doses from rats to humans, in vivo human data on internal doses of inhaled synthetic 

vitreous fibers are limited, and validation exercises with the human model are correspondingly limited. 

Several reviewers of draft versions of this Toxicological Profile disagreed with ATSDR’s selection of 

macrophage aggregation as the critical effect for the MRL. Reasons for not selecting macrophage 

aggregation included: (1) this end point is not a response that is specific to fibers (nonfibrous particles 

can also cause this effect), and (2) it is a reversible and adaptive effect and therefore nonadverse. The 

ATSDR MRL Workgroup acknowledged that although there were confounding effects from nonfibrous 

particles in the principal study, the data in Table 2 show that there was a clear relationship between 

concentrations of fibers in the lung and increasing severity of macrophage aggregation. The MRL 

Workgroup acknowledged the reversibility of macrophage aggregation, but does not consider reversibility 

as a criterion for not selecting a critical effect for MRL derivation. 
 

SYNTHETIC VITREOUS FIBERS A-16 

APPENDIX A 

The ATSDR MRL Workgroup discussed an alternative MRL derivation with collagen deposition as the 

critical effect, but preferred selection of macrophage aggregation as the critical effect. If collagen 

deposition was selected as the critical effect for the MRL, an alternative MRL of 0.02 WHO fibers/cc was 

derived as follows (using a benchmark response=a concentration that would produce an average score of 

1 for bronchoalveolar collagen deposition in a population and a total uncertainty factor of 90: 3 for crossspecies extrapolation, 10 for human variability, and 3 for the selection of a potentially serious adverse 

effect as the critical effect): 

1. [Rat BMCLcollagen deposition] x [cross-species scaling factor] = BMCLcollagen depositionHEC 

32 total fiber/cc x 0.07 = 2.24 WHO fibers/cc = 2 WHO fibers/cc (rounded) 

2. MRL = BMCLcollagen depositionHEC ÷ 90 = 2 ÷ 90 = 0.02 WHO fibers/cc. 

The Workgroup noted the similarity of the values of the MRLs based on macrophage aggregation 

(0.03 WHO fibers/cc) or collagen deposition (0.02 WHO fibers/cc). The approximate 3-fold difference in 

the benchmark concentrations (9 total fibers/cc for macrophage aggregation and 32 total fibers/cc for 

collagen deposition) was offset by the 3-fold difference in the total uncertainty factors (30 for 

macrophage aggregation and 90 for collagen deposition). 

The MRL derivation assumes that rats and humans are equally sensitive to the inflammatory effects of 

refractory ceramic fibers. Understanding of the relative pharmacodynamic sensitivity of rodents and 

humans to synthetic vitreous fibers, asbestos fibers, or nonfibrous particulate matter is poor. Varying 

opinions on the relative sensitivity of rodents and humans to deposited fibers have been expressed by 

Rodelsperger and Woitowitz (1995), Rowe and Springer (1986), Yu and Oberdörster (2000), Maxim and 

McConnell (2001), and Maxim et al. (2003). The uncertainty factor of 3 is used in the MRL derivation to 

account for the uncertainty of the assumption of pharmacodynamic equivalence between rats and humans. 

Available comparative data with other refractory ceramic fibers (e.g., data for RCF2, RCF3, and RCF4 

reported by Mast et al. 1995a) suggest that RCF1 is as potent or more potent in inducing various 

pulmonary effects than other refractory ceramic fibers. Thus, the chronic MRL based on RCF1 data is 

expected to be protective of the public health for exposure to other refractory ceramic fibers. 

A significant contributing factor to the high potency of RCF1 relative to other refractory ceramic fibers is 

the high content of nonfibrous particles in RCF1. Bellmann et al. (2001) have reported that the mass 

concentration of total fibers (particles with aspect ratio >3:1) and nonfibrous particles (with aspect ratios 

<3:1) in RCF1 are 0.76 and 0.26 ng/ng RCF1, respectively. Evidence that the presence of the nonfibrous 

particles can enhance the effects on the lung was provided by comparing responses in rats exposed by 

inhalation for 3 weeks to concentrations of about 125 fibers (with lengths >20 μm)/cc of either RCF1 or a 

sample of refractory ceramic fibers, called RCF1a, in which only 2% of the mass was accounted for by 

nonfibrous particles (Bellmann et al. 2001). Expressed as WHO fibers/cc, the respective mean 

concentrations were 481 fibers/cc for RCF1a and 679 fibers/cc for RCF1. Pulmonary clearance ability 

was markedly depressed by RCF1, but not by RCF1a, and indices of pulmonary inflammation were more 

persistently increased by RCF1 than by RCF1a (Bellmann et al. 2001). 

The ratio of nonfibrous particles:fibers for the RCF1 material used in the 2-year rat bioassay (Mast et al., 

1995a, 1995b) has been reported to be about 3:1 by Bellmann et al. (2001), about 1-2:1 from data 

reported by Mast et al. (1995a, 1995b), and 9:1 by Maxim et al. (1997) and Mast et al. (2000). In 

contrast, workplace air samples (n=10) showed a ratio of about 0.5:1 (Mast et al. 2000; Maxim et al. 

1997). Thus, a key uncertainty associated with the MRL is that the nonfibrous particles likely contributed 
SYNTHETIC VITREOUS FIBERS A-17 

APPENDIX A 

to the observed lung responses to some undetermined degree. As such, the MRL may underestimate the 

daily human exposure that is likely to be without appreciable risk of adverse noncancer health effects, and 

is expected to be protective of public health. 

Bernstein et al. (2001b) conducted an analysis to determine if there was a statistically significant 

relationship between scores for collagen deposition at the bronchoalveolar junction and lung fiber 

concentrations (of various size classes) in the data collected in chronic rat bioassays with five types of 

synthetic vitreous fibers (RCF1, MMVF21—a stone wool, MMVF 11—an insulation glass wool, 

MMVF10—an insulation glass wool, and MMVF22—a slag wool). In the analysis, logistic and 

proportional odds regression models were fit to data for scores for collagen deposition at the bronchoalveolar junction and associated lung fiber concentrations in the rats sacrificed after 24 months of 

exposure. In these analyses, lesion score was the dependent variable and lung fiber concentration (of 

various size classes) was the explanatory variable. Bernstein et al. (2001b; Figure 2) noted that the score 

for collagen deposition showed a statistically significant relationship with increasing lung concentrations 

of the five types of fibers with lengths >20 μm (and not with lung concentrations of fibers in smaller 

length categories). 

In comments provided to ATSDR (ATSDR Docket No. ATSDR-187; January 23, 2003), Dr. Bernstein 

noted that his analysis extended to 10 other pulmonary end points evaluated in these bioassays (including 

scores for macrophage aggregation and bronchiolization), and that he did not find statistically significant 

relationships for these scores with the concentrations of the various types of fibers in the lungs of the rats. 

Dr. Bernstein’s analysis indicates that only the scores for collagen deposition (and not the other 

pulmonary end points) showed a statistically significant relationship with lung burden across the five 

types of synthetic vitreous fibers included in the analysis. Dr. Bernstein interpreted this to mean that, 

among the 11 pulmonary end points evaluated in these bioassays and this analysis, only collagen 

deposition had a statistically significant relationship with fiber lung burden at 24 months. Dr. Bernstein 

proposed that one reason for selecting bronchoalveolar collagen deposition as the critical end point for 

MRL derivation is that there was a lack of association for the other end points with lung fiber 

concentration at 24 months. An alternative interpretation of Dr. Bernstein’s analysis is that it shows that 

only the most biopersistent of the fibers evaluated (i.e., those, such as RCF1, that accumulated to a 

sufficiently high level in the lung after 2 years) produced moderate collagen deposition and that all of the 

fiber types included in the analysis induced the other less adverse responses (such as macrophage 

aggregation and bronchiolization) to degrees that were indistinguishable between fiber types. The data 

from the principal RCF1 study shown in Table A-3 clearly show that the severity of all of the pulmonary 

end points (including scores for macrophage aggregation and bronchiolization) increased with increasing 

exposure level and with increasing lung fiber concentration at 24 months. Thus, even though the 

nonfibrous particles in the RCF1 atmospheres may have contributed to the pulmonary responses in the 

rats, the data show a clear relationship between the severity of macrophage aggregation (and other more 

severe end points) and the internal dose of fibers deposited in the lung. As such, it appears reasonable to 

select macrophage aggregation as the critical effect for MRL derivation. 

The chronic MRL is expected to be appropriately applied to intermediate-duration exposure scenarios, 

based on evidence from interim sacrifice data from the Mast et al. (1995b) bioassay that exposureresponse relationships for pulmonary inflammation and chronic exposure are similar to those for 

intermediate-duration exposure. Scores for pulmonary inflammation progressed to only a limited degree 

with progression from intermediate to chronic duration. For example, mean scores for macrophage 

aggregation in rats exposed to 3, 9, 16, and 30 mg/m3

 at 3 months were 1.7, 2, 2, and 2, respectively. The 

respective scores were 2, 2.3, 3, and 3 at 12 months and 2, 2.5, 3, and 3.2 at 24 months. 
SYNTHETIC VITREOUS FIBERS A-18 

APPENDIX A 

Exposure-response relationships for pulmonary inflammation from acute inhalation exposure to synthetic 

vitreous fibers are inadequately characterized for deriving an acute inhalation MRL for any type of 

synthetic vitreous fiber. 

Any use of the MRL for refractory ceramic fibers in assessing health hazards from the insulation wools 

should acknowledge the evidence that many of the insulation wools are markedly less durable and less 

potent than refractory ceramic fibers (Bernstein et al. 2001a, 2001b; Eastes and Hadley 1996; Eastes et al. 

2000; Hesterberg et al. 1998a). There are data from multiple-exposure-level 2-year rat inhalation 

bioassays on the glass wools, MMVF10 and MMVF11 (Hesterberg et al.1993c; McConnell et al. 1999), 

the slag wool MMVF22 (McConnell et al. 1994), and the rock wool MMVF21 (McConnell et al. 1994) 

that adequately describe exposure-response relationships for nonneoplastic pulmonary effects from 

intermediate- and chronic-duration exposure to these materials. However, lung deposition and clearance 

models for these synthetic vitreous fibers (such as those developed by C.P. Yu and colleagues for RCF1) 

are not yet fully developed to carry out physiologically based dosimetric calculations of human equivalent 

concentrations. When these models are available, they could be used to convert rat exposure 

concentrations to human equivalent concentrations, and use the data for MMVF10, MMVF11, MMVF22, 

and MMVF21 to derive inhalation MRLs for insulation wools. 

There are no adequate data (from multiple-exposure level studies) for deriving inhalation MRLs for the 

other types of synthetic vitreous fibers (special applications glass fibers or continuous filament glass 

fibers that are woven). 

Agency Contact (Chemical Manager): Malcolm Williams, D.V.M., Ph.D. 
SYNTHETIC VITREOUS FIBERS B-1 

APPENDIX B. USER'S GUIDE 

Chapter 1 

Public Health Statement 

This chapter of the profile is a health effects summary written in non-technical language. Its intended 

audience is the general public, especially people living in the vicinity of a hazardous waste site or 

chemical release. If the Public Health Statement were removed from the rest of the document, it would 

still communicate to the lay public essential information about the chemical. 

The major headings in the Public Health Statement are useful to find specific topics of concern. The 

topics are written in a question and answer format. The answer to each question includes a sentence that 

will direct the reader to chapters in the profile that will provide more information on the given topic. 

Chapter 2 

Relevance to Public Health 

This chapter provides a health effects summary based on evaluations of existing toxicologic, 

epidemiologic, and toxicokinetic information. This summary is designed to present interpretive, weightof-evidence discussions for human health end points by addressing the following questions. 

1. What effects are known to occur in humans? 

2. What effects observed in animals are likely to be of concern to humans? 

3. What exposure conditions are likely to be of concern to humans, especially around hazardous 

waste sites? 

The chapter covers end points in the same order that they appear within the Discussion of Health Effects 

by Route of Exposure section, by route (inhalation, oral, and dermal) and within route by effect. Human 

data are presented first, then animal data. Both are organized by duration (acute, intermediate, chronic). 

In vitro data and data from parenteral routes (intramuscular, intravenous, subcutaneous, etc.) are also 

considered in this chapter. 

The carcinogenic potential of the profiled substance is qualitatively evaluated, when appropriate, using 

existing toxicokinetic, genotoxic, and carcinogenic data. ATSDR does not currently assess cancer 

potency or perform cancer risk assessments. Minimal Risk Levels (MRLs) for noncancer end points (if 

derived) and the end points from which they were derived are indicated and discussed. 

Limitations to existing scientific literature that prevent a satisfactory evaluation of the relevance to public 

health are identified in the Chapter 3 Data Needs section. 

Interpretation of Minimal Risk Levels 

Where sufficient toxicologic information is available, ATSDR has derived MRLs for inhalation and oral 

routes of entry at each duration of exposure (acute, intermediate, and chronic). These MRLs are not 
 

 

SYNTHETIC VITREOUS FIBERS B-2 

APPENDIX B 

meant to support regulatory action, but to acquaint health professionals with exposure levels at which 

adverse health effects are not expected to occur in humans. 

MRLs should help physicians and public health officials determine the safety of a community living near 

a chemical emission, given the concentration of a contaminant in air or the estimated daily dose in water. 

MRLs are based largely on toxicological studies in animals and on reports of human occupational 

exposure. 

MRL users should be familiar with the toxicologic information on which the number is based. Chapter 2, 

"Relevance to Public Health," contains basic information known about the substance. Other sections such 

as Chapter 3 Section 3.9, "Interactions with Other Substances,” and Section 3.10, "Populations that are 

Unusually Susceptible" provide important supplemental information. 

MRL users should also understand the MRL derivation methodology. MRLs are derived using a 

modified version of the risk assessment methodology that the Environmental Protection Agency (EPA) 

provides (Barnes and Dourson 1988) to determine reference doses (RfDs) for lifetime exposure. 

To derive an MRL, ATSDR generally selects the most sensitive end point which, in its best judgement, 

represents the most sensitive human health effect for a given exposure route and duration. ATSDR 

cannot make this judgement or derive an MRL unless information (quantitative or qualitative) is available 

for all potential systemic, neurological, and developmental effects. If this information and reliable 

quantitative data on the chosen end point are available, ATSDR derives an MRL using the most sensitive 

species (when information from multiple species is available) with the highest no-observed-adverse-effect 

level (NOAEL) that does not exceed any adverse effect levels. When a NOAEL is not available, a 

lowest-observed-adverse-effect level (LOAEL) can be used to derive an MRL, and an uncertainty factor 

(UF) of 10 must be employed. Additional uncertainty factors of 10 must be used both for human 

variability to protect sensitive subpopulations (people who are most susceptible to the health effects 

caused by the substance) and for interspecies variability (extrapolation from animals to humans). In 

deriving an MRL, these individual uncertainty factors are multiplied together. The product is then 

divided into the inhalation concentration or oral dosage selected from the study. Uncertainty factors used 

in developing a substance-specific MRL are provided in the footnotes of the levels of significant exposure 

(LSE) Tables. 

Chapter 3 

Health Effects 

Tables and Figures for Levels of Significant Exposure (LSE) 

Tables and figures are used to summarize health effects and illustrate graphically levels of exposure 

associated with those effects. These levels cover health effects observed at increasing dose 

concentrations and durations, differences in response by species, MRLs to humans for noncancer end 

points, and EPA's estimated range associated with an upper- bound individual lifetime cancer risk of 1 in 

10,000 to 1 in 10,000,000. Use the LSE tables and figures for a quick review of the health effects and to 

locate data for a specific exposure scenario. The LSE tables and figures should always be used in 

conjunction with the text. All entries in these tables and figures represent studies that provide reliable, 

quantitative estimates of NOAELs, LOAELs, or Cancer Effect Levels (CELs). 
SYNTHETIC VITREOUS FIBERS B-3 

APPENDIX B 

The legends presented below demonstrate the application of these tables and figures. Representative 

examples of LSE Table 3-1 and Figure 3-1 are shown. The numbers in the left column of the legends 

correspond to the numbers in the example table and figure. 

LEGEND 

See Sample LSE Table 3-1 (page B-6) 

(1) Route of Exposure. One of the first considerations when reviewing the toxicity of a substance 

using these tables and figures should be the relevant and appropriate route of exposure. Typically when 

sufficient data exists, three LSE tables and two LSE figures are presented in the document. The three 

LSE tables present data on the three principal routes of exposure, i.e., inhalation, oral, and dermal (LSE 

Table 3-1, 3-2, and 3-3, respectively). LSE figures are limited to the inhalation (LSE Figure 3-1) and oral 

(LSE Figure 3-2) routes. Not all substances will have data on each route of exposure and will not, 

therefore, have all five of the tables and figures. 

(2) Exposure Period. Three exposure periods—acute (less than 15 days), intermediate (15– 

364 days), and chronic (365 days or more)—are presented within each relevant route of exposure. In this 

example, an inhalation study of intermediate exposure duration is reported. For quick reference to health 

effects occurring from a known length of exposure, locate the applicable exposure period within the LSE 

table and figure. 

(3) Health Effect. The major categories of health effects included in LSE tables and figures are 

death, systemic, immunological, neurological, developmental, reproductive, and cancer. NOAELs and 

LOAELs can be reported in the tables and figures for all effects but cancer. Systemic effects are further 

defined in the "System" column of the LSE table (see key number 18). 

(4) Key to Figure. Each key number in the LSE table links study information to one or more data 

points using the same key number in the corresponding LSE figure. In this example, the study 

represented by key number 18 has been used to derive a NOAEL and a Less Serious LOAEL (also see the 

two "18r" data points in sample Figure 3-1). 

(5) Species. The test species, whether animal or human, are identified in this column. Chapter 2, 

"Relevance to Public Health," covers the relevance of animal data to human toxicity and Section 3.4, 

"Toxicokinetics," contains any available information on comparative toxicokinetics. Although NOAELs 

and LOAELs are species specific, the levels are extrapolated to equivalent human doses to derive an 

MRL. 

(6) Exposure Frequency/Duration. The duration of the study and the weekly and daily exposure 

regimen are provided in this column. This permits comparison of NOAELs and LOAELs from different 

studies. In this case (key number 18), rats were exposed to “Chemical x” via inhalation for 6 hours/day, 

5 days/week, for 13 weeks. For a more complete review of the dosing regimen refer to the appropriate 

sections of the text or the original reference paper (i.e., Nitschke et al. 1981). 

(7) System. This column further defines the systemic effects. These systems include respiratory, 

cardiovascular, gastrointestinal, hematological, musculoskeletal, hepatic, renal, and dermal/ocular. 

"Other" refers to any systemic effect (e.g., a decrease in body weight) not covered in these systems. In 

the example of key number 18, one systemic effect (respiratory) was investigated. 
SYNTHETIC VITREOUS FIBERS B-4 

APPENDIX B 

(8) NOAEL. A NOAEL is the highest exposure level at which no harmful effects were seen in the 

organ system studied. Key number 18 reports a NOAEL of 3 ppm for the respiratory system, which was 

used to derive an intermediate exposure, inhalation MRL of 0.005 ppm (see footnote "b"). 

(9) LOAEL. A LOAEL is the lowest dose used in the study that caused a harmful health effect. 

LOAELs have been classified into "Less Serious" and "Serious" effects. These distinctions help readers 

identify the levels of exposure at which adverse health effects first appear and the gradation of effects 

with increasing dose. A brief description of the specific end point used to quantify the adverse effect 

accompanies the LOAEL. The respiratory effect reported in key number 18 (hyperplasia) is a Less 

Serious LOAEL of 10 ppm. MRLs are not derived from Serious LOAELs. 

(10) Reference. The complete reference citation is given in Chapter 9 of the profile. 

(11) CEL. A CEL is the lowest exposure level associated with the onset of carcinogenesis in 

experimental or epidemiologic studies. CELs are always considered serious effects. The LSE tables and 

figures do not contain NOAELs for cancer, but the text may report doses not causing measurable cancer 

increases. 

(12) Footnotes. Explanations of abbreviations or reference notes for data in the LSE tables are found 

in the footnotes. Footnote "b" indicates that the NOAEL of 3 ppm in key number 18 was used to derive 

an MRL of 0.005 ppm. 

LEGEND 

See Sample Figure 3-1 (page B-7) 

LSE figures graphically illustrate the data presented in the corresponding LSE tables. Figures help the 

reader quickly compare health effects according to exposure concentrations for particular exposure 

periods. 

(13) Exposure Period. The same exposure periods appear as in the LSE table. In this example, health 

effects observed within the acute and intermediate exposure periods are illustrated. 

(14) Health Effect. These are the categories of health effects for which reliable quantitative data 

exists. The same health effects appear in the LSE table. 

(15) Levels of Exposure. Concentrations or doses for each health effect in the LSE tables are 

graphically displayed in the LSE figures. Exposure concentration or dose is measured on the log scale 

"y" axis. Inhalation exposure is reported in mg/m3

 or ppm and oral exposure is reported in mg/kg/day. 

(16) NOAEL. In this example, the open circle designated 18r identifies a NOAEL critical end point in 

the rat upon which an intermediate inhalation exposure MRL is based. The key number 18 corresponds to 

the entry in the LSE table. The dashed descending arrow indicates the extrapolation from the exposure 

level of 3 ppm (see entry 18 in the Table) to the MRL of 0.005 ppm (see footnote "b" in the LSE table). 

(17) CEL. Key number 38r is one of three studies for which CELs were derived. The diamond 

symbol refers to a CEL for the test species-mouse. The number 38 corresponds to the entry in the LSE 

table. 

(18) Estimated Upper-Bound Human Cancer Risk Levels. This is the range associated with the upperbound for lifetime cancer risk of 1 in 10,000 to 1 in 10,000,000. These risk levels are derived from the 
SYNTHETIC VITREOUS FIBERS B-5 

APPENDIX B 

EPA's Human Health Assessment Group's upper-bound estimates of the slope of the cancer dose response 

curve at low dose levels (q1*). 

(19) Key to LSE Figure. The Key explains the abbreviations and symbols used in the figure. 
1 3 4 

SAMPLE 

→ Table 3-1. Levels of Significant Exposure to [Chemical x] – Inhalation 

LOAEL (effect) Exposure Less serious Serious (ppm) frequency/ NOAEL (ppm) Key to figurea Species duration System (ppm) Refer

2 →INTERMEDIATE EXPOSURE 

5 6 7 8 9 10 

→Systemic ↓ ↓ ↓ ↓ ↓ ↓

18 Rat 13 wk Resp 3b 10 (hyperplasia) 

→ 5 d/wk 

6 hr/d 

Nitsch

CHRONIC EXPOSURE 

Cancer 11 

↓

38 Rat 18 mo 20 (CEL, multiple Wong 

5 d/wk 7 hr/d 

organs) 

39 Rat 89-104 wk 10 (CEL, lung tumors, NTP 1

5 d/wk 6 hr/d 

nasal tumors) 

40 Mouse 79-103 wk 10 (CEL, lung tumors, NTP 1

5 d/wk hemangiosarcomas) 6 hr/d 

12 →a The number corresponds to entries in Figure 3-1. 

b Used to derive an intermediate inhalation Minimal Risk Level (MRL) of 5x10-3 ppm; dose adjusted for intermittent expos

by an uncertainty factor of 100 (10 for extrapolation from animal to humans, 10 for human variability). 


SYNTHETIC VITREOUS FIBERS C-1 

APPENDIX C. ACRONYMS, ABBREVIATIONS, AND SYMBOLS 

ACGIH American Conference of Governmental Industrial Hygienists 

ACOEM American College of Occupational and Environmental Medicine 

ADI acceptable daily intake 

ADME absorption, distribution, metabolism, and excretion 

AED atomic emission detection 

AFID alkali flame ionization detector 

AFOSH Air Force Office of Safety and Health 

ALT alanine aminotransferase 

AML acute myeloid leukemia 

AOAC Association of Official Analytical Chemists 

AOEC Association of Occupational and Environmental Clinics 

AP alkaline phosphatase 

APHA American Public Health Association 

AST aspartate aminotransferase 

atm atmosphere 

ATSDR Agency for Toxic Substances and Disease Registry 

AWQC Ambient Water Quality Criteria 

BAT best available technology 

BCF bioconcentration factor 

BEI Biological Exposure Index 

BMD benchmark dose 

BMR benchmark response 

BSC Board of Scientific Counselors 

C centigrade 

CAA Clean Air Act 

CAG Cancer Assessment Group of the U.S. Environmental Protection Agency 

CAS Chemical Abstract Services 

CDC Centers for Disease Control and Prevention 

CEL cancer effect level 

CELDS Computer-Environmental Legislative Data System 

CERCLA Comprehensive Environmental Response, Compensation, and Liability Act 

CFR Code of Federal Regulations 

Ci curie 

CI confidence interval 

CL ceiling limit value 

CLP Contract Laboratory Program 

cm centimeter 

CML chronic myeloid leukemia 

CPSC Consumer Products Safety Commission 

CWA Clean Water Act 

DHEW Department of Health, Education, and Welfare 

DHHS Department of Health and Human Services 

DNA deoxyribonucleic acid 

DOD Department of Defense 

DOE Department of Energy 

DOL Department of Labor 

DOT Department of Transportation 
 

SYNTHETIC VITREOUS FIBERS C-2 

APPENDIX C 

DOT/UN/ Department of Transportation/United Nations/ 

NA/IMCO North America/International Maritime Dangerous Goods Code 

DWEL drinking water exposure level 

ECD electron capture detection 

ECG/EKG electrocardiogram 

EEG electroencephalogram 

EEGL Emergency Exposure Guidance Level 

EPA Environmental Protection Agency 

F Fahrenheit 

F1 first-filial generation 

FAO Food and Agricultural Organization of the United Nations 

FDA Food and Drug Administration 

FEMA Federal Emergency Management Agency 

FIFRA Federal Insecticide, Fungicide, and Rodenticide Act 

FPD flame photometric detection 

fpm feet per minute 

FR Federal Register 

FSH follicle stimulating hormone 

g gram 

GC gas chromatography 

gd gestational day 

GLC gas liquid chromatography 

GPC gel permeation chromatography 

HPLC high-performance liquid chromatography 

HRGC high resolution gas chromatography 

HSDB Hazardous Substance Data Bank 

IARC International Agency for Research on Cancer 

IDLH immediately dangerous to life and health 

ILO International Labor Organization 

IRIS Integrated Risk Information System 

Kd adsorption ratio 

kg kilogram 

kkg metric ton 

Koc organic carbon partition coefficient 

Kow octanol-water partition coefficient 

L liter 

LC liquid chromatography 

LC50 lethal concentration, 50% kill 

LCLo lethal concentration, low 

LD50 lethal dose, 50% kill 

LDLo lethal dose, low 

LDH lactic dehydrogenase 

LH luteinizing hormone 

LOAEL lowest-observed-adverse-effect level 

LSE Levels of Significant Exposure 

LT50 lethal time, 50% kill 

m meter 

MA trans,trans-muconic acid 

MAL maximum allowable level 

mCi millicurie 

MCL maximum contaminant level 
 

SYNTHETIC VITREOUS FIBERS C-3 

APPENDIX C 

MCLG maximum contaminant level goal 

MF modifying factor 

MFO mixed function oxidase 

mg milligram 

mL milliliter 

mm millimeter 

mmHg millimeters of mercury 

mmol millimole 

mppcf millions of particles per cubic foot 

MRL Minimal Risk Level 

MS mass spectrometry 

NAAQS National Ambient Air Quality Standard 

NAS National Academy of Science 

NATICH National Air Toxics Information Clearinghouse 

NATO North Atlantic Treaty Organization 

NCE normochromatic erythrocytes 

NCEH National Center for Environmental Health 

NCI National Cancer Institute 

ND not detected 

NFPA National Fire Protection Association 

ng nanogram 

NHANES National Health and Nutrition Examination Survey 

NIEHS National Institute of Environmental Health Sciences 

NIOSH National Institute for Occupational Safety and Health 

NIOSHTIC NIOSH's Computerized Information Retrieval System 

NLM National Library of Medicine 

nm nanometer 

nmol nanomole 

NOAEL no-observed-adverse-effect level 

NOES National Occupational Exposure Survey 

NOHS National Occupational Hazard Survey 

NPD nitrogen phosphorus detection 

NPDES National Pollutant Discharge Elimination System 

NPL National Priorities List 

NR not reported 

NRC National Research Council 

NS not specified 

NSPS New Source Performance Standards 

NTIS National Technical Information Service 

NTP National Toxicology Program 

ODW Office of Drinking Water, EPA 

OERR Office of Emergency and Remedial Response, EPA 

OHM/TADS Oil and Hazardous Materials/Technical Assistance Data System 

OPP Office of Pesticide Programs, EPA 

OPPT Office of Pollution Prevention and Toxics, EPA 

OPPTS Office of Prevention, Pesticides and Toxic Substances, EPA 

OR odds ratio 

OSHA Occupational Safety and Health Administration 

OSW Office of Solid Waste, EPA 

OTS Office of Toxic Substances 

OW Office of Water 
SYNTHETIC VITREOUS FIBERS C-4 

APPENDIX C 

OWRS Office of Water Regulations and Standards, EPA 

PAH polycyclic aromatic hydrocarbon 

PBPD physiologically based pharmacodynamic 

PBPK physiologically based pharmacokinetic 

PCE polychromatic erythrocytes 

PEL permissible exposure limit 

pg picogram 

PHS Public Health Service 

PID photo ionization detector 

pmol picomole 

PMR proportionate mortality ratio 

ppb parts per billion 

ppm parts per million 

ppt parts per trillion 

PSNS pretreatment standards for new sources 

RBC red blood cell 

REL recommended exposure level/limit 

RfC reference concentration 

RfD reference dose 

RNA ribonucleic acid 

RQ reportable quantity 

RTECS Registry of Toxic Effects of Chemical Substances 

SARA Superfund Amendments and Reauthorization Act 

SCE sister chromatid exchange 

SGOT serum glutamic oxaloacetic transaminase 

SGPT serum glutamic pyruvic transaminase 

SIC standard industrial classification 

SIM selected ion monitoring 

SMCL secondary maximum contaminant level 

SMR standardized mortality ratio 

SNARL suggested no adverse response level 

SPEGL Short-Term Public Emergency Guidance Level 

STEL short term exposure limit 

STORET Storage and Retrieval 

TD50 toxic dose, 50% specific toxic effect 

TLV threshold limit value 

TOC total organic carbon 

TPQ threshold planning quantity 

TRI Toxics Release Inventory 

TSCA Toxic Substances Control Act 

TWA time-weighted average 

UF uncertainty factor 

U.S. United States 

USDA United States Department of Agriculture 

USGS United States Geological Survey 

VOC volatile organic compound 

WBC white blood cell 

WHO World Health Organization 
SYNTHETIC VITREOUS FIBERS C-5 

APPENDIX C 

> ≥

= 

< ≤

% αβγδ

μm

μg q1

* 

– 

+ 

(+) 

(–) 

greater than 

greater than or equal to 

equal to 

less than 

less than or equal to 

percent 

alpha 

beta 

 gamma 

delta 

 micrometer 

microgram 

cancer slope factor 

negative 

positive 

weakly positive result 

weakly negative result 

SYNTHETIC VITREOUS FIBERS D-1 

APPENDIX D. INDEX 

absorbed dose............................................................................................................................................ 140 

adipose tissue ............................................................................................................................................ 117 

adsorption.................................................................................................................................................. 204 

alveolar retention models.................................................................................................................. 126, 128 

ambient air ........................................................................................ 179, 182, 184, 185, 189, 193, 202, 204 

benchmark dose modeling approach........................................................................................................... 23 

bioaccumulation........................................................................................................................................ 204 

biodegradation..................................................................................................................................... 15, 179 

biomarker .................................................................................................. 139, 140, 141, 155, 156, 207, 214 

body weight effects ............................................................................................................................. 31, 108 

breast milk............................................................................................................................................. 8, 200 

bronchoalveolar lavage fluid....................................................................................................... 87, 140, 214 

C102/C104 blend fibrous glass........................................................................... 19, 20, 86, 90, 97, 149, 151 

cancer ..............................5, 6, 7, 16, 18, 20, 21, 22, 79, 96, 98, 99, 100, 101, 102, 104, 107, 110, 128, 135, 

138, 141, 142, 143, 151, 154, 155, 159, 193, 214, 217 

carcinogen......................................................................................................................... 8, 21, 22, 217, 219 

carcinogenic .................................................................................. 7, 20, 22, 29, 30, 105, 110, 134, 217, 219
 

carcinogenicity.....................................7, 18, 20, 21, 22, 86, 97, 98, 101, 103, 104, 105, 106, 132, 217, 219 

carcinoma......................................................................... 20, 96, 97, 102, 104 103, 105, 106, 107, 134, 151 

cardiovascular ............................................................................................................................. 95, 107, 108 

cardiovascular effects.................................................................................................................................. 94 

chest x-ray............................................................................................... 10, 18, 83, 141, 142, 154, 156, 214 

chromosomal aberrations .................................................................................................................. 111, 153 

chronic inhalation MRL.................................................................................................... 135, 149, 150, 152 

clearance ...............17, 21, 23, 25, 88, 91, 104, 110, 112, 113, 115, 116, 117, 118, 119, 120, 121, 123, 124, 

126, 127, 128, 130, 131, 132, 134, 143, 144, 148, 156, 157, 159, 160, 181 

Code 104/475 glass fiber ............................................................................................................................ 19 

continuous filament...............................2, 7, 13, 15, 16, 21, 22, 27, 94, 95, 96, 99, 100, 112, 118, 120, 163, 

166, 168, 171, 174, 217, 218, 219 

counting rules A................................................................................................................ 182, 186, 188, 207 

counting rules B ................................................................................................................ 182, 186, 188, 208 

cristobalite................................................................................................................. 165, 181, 198, 200, 202 

death........................................................................................ 29, 31, 80, 94, 95, 98, 99, 100, 107, 108, 141 

decreased pulmonary function ........................................................................................ 80, 82, 83, 143, 144 

deposition and clearance models..................................................... 22, 23, 27, 128, 135, 149, 150, 152, 158 

dermal effects.................................................................................................................................... 108, 109 

dissolution.....................................15, 17, 110, 115, 116, 117, 118, 119, 120, 121, 122, 123, 125, 127, 130, 

131, 132, 134, 145, 156, 158, 159, 166, 179, 184 

DNA.................................................................................................................. 111, 133, 134, 139, 143, 153 

EDXA ....................................................................................................................................... 185, 209, 210 

elimination half-time................................................................................................................................. 121 

endocrine............................................................................................................................. 31, 107, 108, 136 

epidemiologic studies.......................................................................................................................... 21, 217 

erythema.................................................................................................................................................... 108 

FEF25-75 .................................................................................................................................................... 81 

fetus........................................................................................................................................... 137, 138, 160 

FEV1..................................................................................................................................................... 81, 82 

FVC....................................................................................................................................................... 80, 82 
SYNTHETIC VITREOUS FIBERS D-2 

APPENDIX D 

gastrointestinal effects ................................................................................................................................ 95 

GB100R .......................................................................................................................... 19, 90, 97, 149, 151
 

general population............................................................................................. 139, 150, 179, 188, 189, 204
 

genotoxic............................................................................................................................. 29, 110, 134, 153 

genotoxicity............................................................................................................................... 110, 130, 153 

glass wool .......2, 4, 5, 6, 7, 11, 13, 15, 16, 17, 19, 20, 21, 22, 27, 82, 83, 84, 85, 86, 89, 90, 91, 92, 93, 94, 

95, 96, 97, 98, 99, 100, 101, 102, 103, 105, 106, 108, 109, 110, 111, 113, 116, 118,

 119, 120, 127, 149, 150, 151, 152, 157, 163, 165, 166, 168, 169, 171, 175, 176, 

179, 186, 189, 190, 194, 202, 217, 218, 220 

half-life...................................................................................................................................................... 139 

hepatic effects ............................................................................................................................................. 95 

hydroxyl radical ................................................................................................................................ 111, 153 

IARC...............................................................7, 13, 14, 21, 95, 99, 103, 110, 133, 134, 145, 160, 163, 168, 

171, 174, 175, 185, 190, 203, 217, 218, 219 

immune system ......................................................................................................................................... 154 

immunological .................................................................................................................................... 29, 154 

immunological effects............................................................................................................................... 154 

inhalation MRLs ................................................................................................... 27, 30, 150, 152, 157, 159 

Integrated Risk Information System (see IRIS).......................................................................... 22, 217, 219 

IRIS (see Integrated Risk Information System).......................................................................... 22, 217, 219 

irritation effects................................................................................................................................. 144, 159 

lymphatic .......................................................................................................................... 102, 115, 130, 158 

lymphoreticular......................................................................................................................................... 154 

metabolic effects ....................................................................................................................................... 107 

micronuclei ....................................................................................................................................... 111, 153 

mineral wool ................................................................. 13, 83, 102, 165, 171, 174, 175, 187, 194, 203, 218 

MMVF10 .................19, 20, 22, 27, 86, 90, 97, 105, 106, 111, 119, 120, 124, 127, 133, 149, 150, 151, 152 

MMVF10a ............................................................................................................................ 20, 90, 105, 113 

MMVF11 .........................................19, 20, 22, 27, 86, 90, 97, 105, 106, 120, 124, 127, 149, 150, 151, 152 

MMVF21 ...................................19, 20, 22, 27, 86, 92, 93, 97, 107, 120, 121, 127, 133, 136, 149, 150, 152 

MMVF22 .........................................................19, 20, 22, 27, 86, 93, 97, 106, 120, 127, 149, 150, 151, 152 

MMVF33 .............................................................................. 19, 20, 86, 90, 97, 98, 105, 113, 120, 149, 151 

mucociliary ............................................17, 95, 113, 115, 116, 117, 123, 125, 127, 131, 145, 156, 157, 159 

mucociliary translocation.......................................................................................................... 123, 125, 145 

National Toxicology Program............................................................................................. 21, 146, 217, 219 

neoplastic ...................................................................................................... 26, 85, 133, 148, 151, 156, 160 

neurobehavioral......................................................................................................................................... 137 

NIOSH fiber counting rules ........................................................................................................................ 79 

nonfibrous particles in the RCF1 ................................................................................................................ 25 

nonmalignant respiratory disease........................................................ 18, 80, 81, 83, 84, 102, 135, 151, 155 

ocular effects............................................................................................................................................. 109 

odds ratio....................................................................................................................................... 80, 81, 101 

PCM .....................................................15, 181, 182, 185, 186, 189, 190, 193, 207, 208, 209, 210, 211, 213 

pharmacodynamic............................................................................................................................. 125, 135 

pharmacokinetic.................................................................................. 16, 125, 126, 130, 135, 137, 138, 160 

photolysis ............................................................................................................................................ 15, 179 

pleural plaques .......................................................... 5, 10, 18, 79, 80, 82, 83, 130, 142, 150, 151, 155, 156 

pulmonary fibrosis ...................................................6, 7, 16, 25, 93, 104, 110, 135, 142, 143, 151, 159, 214 

pulmonary inflammation.......................6, 7, 16, 18, 19, 22, 25, 27, 87, 88, 89, 90, 91, 92, 93, 94, 149, 151, 

152, 156, 157, 159 

pulmonary or pleural fibrosis.......................................................................... 16, 19, 20, 141, 142, 214, 215 
SYNTHETIC VITREOUS FIBERS D-3 

APPENDIX D 

quartz ........................................................................................................................ 165, 181, 198, 200, 202 

RCF1.......................................18, 19, 20, 22, 23, 24, 25, 26, 27, 85, 86, 87, 88, 89, 97, 103, 104, 105, 111, 

118, 127, 128, 131, 133, 135, 136, 148, 149, 151, 152 

RCF1a ............................................................................................................................. 25, 86, 88, 120, 152 

RCF2..................................................................................................... 19, 20, 86, 88, 89, 97, 104, 149, 151 

RCF3..................................................................................................... 19, 20, 86, 88, 89, 97, 104, 149, 151 

RCF4..................................................................................................... 19, 20, 86, 88, 89, 97, 104, 149, 151 

refractory ceramic .................2, 5, 6, 7, 13, 15, 16, 17, 18, 19, 20, 21, 22, 25, 27, 31, 79, 80, 81, 85, 86, 87, 

89, 94, 97, 98, 103, 104, 108, 110, 111, 114, 118, 126, 128, 130, 133, 134, 

135, 136, 140, 143, 144, 149, 150, 151, 152, 154, 155, 156, 157, 158, 

163, 164, 165, 168, 170, 171, 175, 177, 181, 182, 184, 189, 190, 

193, 198, 199, 200, 202, 203, 214, 217, 219, 220 

renal effects................................................................................................................................................. 96 

respiratory tract irritation ...................................................................................................................... 17, 82 

retention ...................................................................................................... 23, 126, 127, 134, 157, 158, 159 

rock wool ............2, 11, 13, 15, 16, 17, 18, 19, 20, 21, 22, 27, 31, 82, 83, 84, 85, 92, 93, 94, 95, 96, 98, 99, 

102, 106, 107, 108, 110, 119, 120, 121, 127, 135, 149, 150, 151, 152, 154, 155, 

157, 165, 166, 168, 171, 175, 179, 182, 186, 189, 193, 217, 218, 219, 220 

SEM .................................................................................................... 15, 168, 169, 182, 186, 209, 210, 212 

slag wool .......2, 4, 6, 7, 11, 13, 15, 16, 17, 18, 19, 20, 21, 22, 27, 31, 82, 83, 84, 85, 86, 93, 94, 95, 96, 98, 

99, 100, 101, 103, 106, 110, 118, 119, 126, 127, 135, 149, 150, 151, 152, 154, 155, 

163, 165, 166, 168, 171, 175, 179, 182, 184, 190, 193, 217, 218, 219, 220 

solubility ................................................................................................................................................... 166 

special-purpose 104E-glass fiber ........................................................................................................ 19, 149 

TEM ............................................................................ 15, 168, 182, 185, 186, 189, 209, 210, 211, 212, 213 

toxicokinetic........................................................................................................................ 29, 156, 158, 159 

tridymite.................................................................................................................... 165, 181, 198, 200, 202 

tumors ................................................................................. 10, 20, 21, 25, 97, 103, 104, 105, 106, 130, 132 

vapor pressure ........................................................................................................................................... 165 

WHO fiber counting rules........................................................................................................................... 31 

X607.......................................................................................................................... 19, 20, 94, 97, 149, 151 

Yu...........................................................23, 27, 112, 113, 114, 126, 127, 128, 129, 130, 134, 157, 158, 201