TOXICOLOGICAL PROFILE FOR
 

BERYLLIUM
 

U.S. DEPARTMENT OF HEALTH AND HUMAN SERVICES
 

Public Health Service
 

Agency for Toxic Substances and Disease Registry
 

September 2002 
BERYLLIUM 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. 
BERYLLIUM iii 

UPDATE STATEMENT
 

Toxicological profiles are revised and republished as necessary, but no less than once every three years. 

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, E-29
 

Atlanta, Georgia 30333
 

V 

FOREWORD 

This toxicological profile is prepared in accordance with guidelines* developed by the Agency for 

Toxic Substances and Disease Registry (ATSDR) and the Environmental Protection Agency (EPA). The 

original guidelines were published in the Federal Register on April 17, 1987. Each profile will be revised 

and republished as necessary. 

The ATSDR to&ological profile succinctly characterizes the toxicologic and adverse health 

effects information for the hazardous substance described therein. Each peer-reviewed profile identifies 

and reviews the key literature that describes a hazardous substance's toxicologic properties. Other 

pertinent literature is also presented, but is described in less detail than the key studies. The profile is not 

intended to be an exhaustive document; however, more comprehensive sources of specialty information 

are referenced. 

The focus of the profiles is on health and toxicologic information; therefore, each toxicological 

profile begins with a public health statement that describes, in nontechnical language, a substance's 

relevant toxicological properties. Following the public health statement is information concerning levels 

of Significant human exposure and, where known, significant health effects. The adequacy of 

information to determine a substance's health effects is described in a health effects summary. Data 

needs that are of significance to protection of public health are identified by ATSDR and EPA. 

Each profile includes the following: 

The examination, summary, and interpretation of available toxicologic information and 

epidemiologic evaluations on a hazardous substance to ascertain the levels of significant 

human exposure for the substance and the associated acute, subacute, and chronic health 

effects; 

A determination of whether adequate information on the health effects of each substance is 

available or in the process of development to determine levels of exposure that present a 

significant risk to human health of acute, subacute, and chronic health effects; and 

Where appropriate, identification of toxicologic testing needed to identify the types or levels 

of exposure that may present significant risk of adverse health effects in humans. 

The principal audiences for the toxicological profiles are health professionals at the federal, state, 

and local levels; interested private sector organizations and groups; and members of the public. 

This profile reflects ATSDR's assessment of all relevant toxicologic testing and information that 

has been peer-reviewed. Staff of the Centers for Disease Control and Prevention and other federal 

scientists have also reviewed the profile. In addition, this profile has been peer-reviewed by a 

nongovernmental panel and was made available for public review. Final responsibility for the contents 

and views expressed in this toxicological profile resides with ATSDR. 

Administrator 

Agency for Toxic Substances and 

Disease Registry 
BERYLLIUM vi 

*Legislative Background 

The toxicological profiles are developed in response to the Superfund Amendments and 

Reauthorization Act (SARA) of 1986 (Public law 99-499) which amended the Comprehensive 

Environmental Response, Compensation, and Liability Act of 1980 (CERCLA or Superfund). This 

public law directed ATSDR to prepared toxicological profiles for hazardous substances most commonly 

found at facilities on the CERCLA National Priorities List and that pose the most significant potential 

threat to human health, as determined by ATSDR and the EPA. The availability of the revised priority 

list of 275 hazardous substances was announced in the Federal Register on November 17, 1997 (62 FR 

61332). For prior versions of the list of substances, see Federal Register notices dated April 29, 1996 (61 

FR 18744); April 17, 1987 (52 FR 12866); October 20, 1988 (53 FR 41280); October 26, 1989 (54 FR 

43619); October 17, 1990 (55 FR 42067); October 17, 1991 (56 FR 52166); October 28, 1992 (57 FR 

48801); and February 28, 1994 (59 FR 9486). Section 104(i)(3) of CERCLA, as amended, directs the 

Administrator of ATSDR to prepare a toxicological profile for each substance on the list. 
 

 

BERYLLIUM 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 

route of exposure, by type of health effect (death, systemic, immunologic, reproductive), 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: (404) 498-0057 

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 and Environmental Exposures; Cholinesterase-Inhibiting Pesticide 

Toxicity; and numerous chemical-specific case studies.Managing Hazardous Materials Incidents 
BERYLLIUM viii 

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@dgs.dgsys.com • AOEC Clinic Director: http://occ-envmed.mc.duke.edu/oem/aoec.htm. 

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. 
BERYLLIUM ix 

CONTRIBUTORS 

CHEMICAL MANAGER(S)/AUTHORS(S): 

Cassandra Smith, M.S.
 

ATSDR, Division of Toxicology, Atlanta, GA
 

Lisa Ingerman, Ph.D., DABT
 

Syracuse Research Corporation, North Syracuse, NY
 

Richard Amata, 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. 

BERYLLIUM xi 

PEER REVIEW
 

A peer review panel was assembled for beryllium. The panel consisted of the following members: 

1.	 Dr. Derek J. Hodgson, University of Nebraska at Omaha, Omaha, NE. 

2.	 Dr. Laurence Holland, Private Consultant, Los Alamos, NM. 

3.	 Dr. Hanspeter Witschi, Center for Health and the Environment, University of California Davis, 

CA 95615. 

4.	 Dr. Finis Cavendar, Adjunct Professor, Curriculum in Toxicology, University of North Carolina 

at Chapel Hill, Chapel Hill, NC. 

These experts collectively have knowledge of beryllium's 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. 

BERYLLIUM xiii 

CONTENTS
 

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

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

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

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

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

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

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

1.1 WHAT IS BERYLLIUM? ..................................................... 1 
 

1.2 WHAT HAPPENS TO BERYLLIUM WHEN IT ENTERS THE ENVIRONMENT? ...... 2 
 

1.3 HOW MIGHT I BE EXPOSED TO BERYLLIUM? ................................. 4 
 

1.4 HOW CAN BERYLLIUM ENTER AND LEAVE MY BODY? ....................... 5 
 

1.5 HOW CAN BERYLLIUM AFFECT MY HEALTH? ................................ 6 
 

1.6	 HOW CAN BERYLLIUM AFFECT CHILDREN? ................................. 7 
 

1.7 	 HOW CAN FAMILIES REDUCE THE RISK OF EXPOSURE TO BERYLLIUM? ....... 8 
 

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

BERYLLIUM? .............................................................. 8 
 

1.9	 WHAT RECOMMENDATIONS HAS THE FEDERAL GOVERNMENT MADE TO
 

PROTECT HUMAN HEALTH ? ................................................ 9 
 

1.10 WHERE CAN I GET MORE INFORMATION? .................................. 10 
 

2. RELEVANCE TO PUBLIC HEALTH ............................................... 11 
 

2.1	 BACKGROUND AND ENVIRONMENTAL EXPOSURES TO BERYLLIUM IN THE
 

UNITED STATES .......................................................... 11 
 

2.2	 SUMMARY OF HEALTH EFFECTS ........................................... 11 
 

2.3 	 MINIMAL RISK LEVELS ................................................... 16 
 

3. HEALTH EFFECTS .............................................................. 19 
 

3.1 INTRODUCTION .......................................................... 19 
 

3.2 DISCUSSION OF HEALTH EFFECTS BY ROUTE OF EXPOSURE ................. 19 
 

3.2.1 Inhalation Exposure .................................................. 21 
 

3.2.1.1 Death ..................................................... 21 
 

3.2.1.2 Systemic Effects ............................................ 23 
 

3.2.1.3 Immunological and Lymphoreticular Effects ...................... 62 
 

3.2.1.4 Neurological Effects ......................................... 64 
 

3.2.1.5 Reproductive Effects ......................................... 64 
 

3.2.1.6 Developmental Effects ....................................... 64 
 

3.2.1.7 Cancer .................................................... 65 
 

3.2.2 Oral Exposure ...................................................... 73
 

3.2.2.1 Death ..................................................... 74 
 

3.2.2.2 Systemic Effects ............................................ 74 
 

3.2.2.3 Immunological and Lymphoreticular Effects ...................... 85 
 
 

BERYLLIUM xiv 

3.2.2.4 Neurological Effects ......................................... 86 
 

3.2.2.5 Reproductive Effects ......................................... 86 
 

3.2.2.6 Developmental Effects ....................................... 87 
 

3.2.2.7 Cancer .................................................... 87 
 

3.2.3 Dermal Exposure .................................................... 88 
 

3.2.3.1 Death ..................................................... 88 
 

3.2.3.2 Systemic Effects ............................................ 88 
 

3.2.3.3 Immunological and Lymphoreticular Effects ...................... 89 
 

3.2.3.4 Neurological Effects ......................................... 90 
 

3.2.3.5 Reproductive Effects ......................................... 90 
 

3.2.3.6 Developmental Effects ....................................... 90 
 

3.2.3.7 Cancer .................................................... 90 
 

3.2.4 Other Routes of Exposure ............................................. 90 
 

3.3 GENOTOXICITY .......................................................... 94 
 

3.4 TOXICOKINETICS ......................................................... 96 
 

3.4.1 Absorption ......................................................... 96 
 

3.4.1.1 Inhalation Exposure .......................................... 96 
 

3.4.1.2 Oral Exposure .............................................. 96 
 

3.4.1.3 Dermal Exposure ............................................ 97 
 

3.4.2 	 Distribution ........................................................ 97 
 

3.4.2.1 Inhalation Exposure .......................................... 98 
 

3.4.2.2 Oral Exposure .............................................. 99 
 

3.4.2.3 Dermal Exposure ............................................ 99 
 

3.4.2.4 Other Routes of Exposure ..................................... 99
 

3.4.3 	 Metabolism ........................................................ 100 
 

3.4.4 	 Elimination and Excretion ............................................ 100 
 

3.4.4.1 Inhalation Exposure ......................................... 100 
 

3.4.4.2 Oral Exposure ............................................. 102 
 

3.4.4.3 Dermal Exposure ........................................... 102 
 

3.4.5	 Physiologically Based Pharmacokinetic (PBPK)/
 

Pharmacodynamic (PD) Models ....................................... 102 
 

3.5 MECHANISMS OF ACTION ................................................ 105 
 

3.5.1 	 Pharmacokinetic Mechanisms ......................................... 105 
 

3.5.2 	 Mechanisms of Toxicity .............................................. 105 
 

3.5.3 	 Animal-to-Human Extrapolations ...................................... 107 
 

3.6 TOXICITIES MEDIATED THROUGH THE NEUROENDOCRINE AXIS ............ 107 
 

3.7 CHILDREN’S SUSCEPTIBILITY ............................................ 109 
 

3.8 BIOMARKERS OF EXPOSURE AND EFFECT ................................. 111
 

3.8.1 Biomarkers Used to Identify or Quantify Exposure to Beryllium .............. 112
 

3.8.2 Biomarkers Used to Characterize Effects Caused by Beryllium ............... 115 
 

3.9 INTERACTIONS WITH OTHER CHEMICALS ................................. 116 
 

3.10 POPULATIONS THAT ARE UNUSUALLY SUSCEPTIBLE ...................... 117 
 

3.11 METHODS FOR REDUCING TOXIC EFFECTS ................................ 119 
 

3.11.1 Reducing Peak Absorption Following Exposure ........................... 120 
 

3.11.2 Reducing Body Burden .............................................. 120 
 

3.11.3 Interfering with the Mechanism of Action for Toxic Effects .................. 121 
 

3.12 ADEQUACY OF THE DATABASE ........................................... 122
 

3.12.1	 Existing Information on Health Effects of Beryllium ....................... 123 
 

3.12.2 	 Identification of Data Needs .......................................... 125 
 

3.12.3	 Ongoing Studies .................................................... 134
 
BERYLLIUM xv 

4. CHEMICAL AND PHYSICAL INFORMATION ...................................... 137 
 

4.1 CHEMICAL IDENTITY .................................................... 137 
 

4.2 PHYSICAL AND CHEMICAL PROPERTIES ................................... 137 
 

5. PRODUCTION, IMPORT/EXPORT, USE, AND DISPOSAL ............................ 143 
 

5.1 PRODUCTION ........................................................... 143 
 

5.2 IMPORT/EXPORT ........................................................ 144 
 

5.3 USE ..................................................................... 144 
 

5.4 DISPOSAL ............................................................... 147 
 

6. POTENTIAL FOR HUMAN EXPOSURE ........................................... 149 
 

6.1 OVERVIEW .............................................................. 149 
 

6.2 RELEASES TO THE ENVIRONMENT ........................................ 151 
 

6.2.1 Air .............................................................. 152 
 

6.2.2 Water ............................................................ 157 
 

6.2.3 Soil .............................................................. 158 
 

6.3 ENVIRONMENTAL FATE .................................................. 159 
 

6.3.1 Transport and Partitioning ............................................ 159 
 

6.3.2 Transformation and Degradation ....................................... 161 
 

6.3.2.1 Air ...................................................... 161 
 

6.3.2.2 Water .................................................... 161 
 

6.3.2.3 Sediment and Soil .......................................... 164 
 

6.3.2.4 Other Media ............................................... 164 
 

6.4 LEVELS MONITORED OR ESTIMATED IN THE ENVIRONMENT ............... 164 
 

6.4.1 Air .............................................................. 164 
 

6.4.2 Water ............................................................ 165 
 

6.4.3 Sediment and Soil .................................................. 166 
 

6.4.4 Other Environmental Media ........................................... 169 
 

6.5 GENERAL POPULATION AND OCCUPATIONAL EXPOSURE .................. 173 
 

6.6 EXPOSURES OF CHILDREN ............................................... 175 
 

6.7 POPULATIONS WITH POTENTIALLY HIGH EXPOSURES ...................... 177 
 

6.8 ADEQUACY OF THE DATABASE ........................................... 178 
 

6.8.1 Identification of Data Needs .......................................... 178 
 

6.8.2 Ongoing Studies .................................................... 181 
 

7. ANALYTICAL METHODS ....................................................... 183 
 

7.1 BIOLOGICAL MATERIALS ................................................ 183 
 

7.2 ENVIRONMENTAL SAMPLES .............................................. 186 
 

7.3 ADEQUACY OF THE DATABASE ........................................... 190 
 

7.3.1 Identification of Data Needs .......................................... 190 
 

7.3.2 Ongoing Studies .................................................... 191 
 

8. REGULATIONS AND ADVISORIES .............................................. 193 
 

9. REFERENCES ................................................................. 201 
 

10. GLOSSARY .................................................................. 241 
 
BERYLLIUM xvi 

APPENDICES
 

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

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

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

INDEX ....................................................................... D-1 
 
BERYLLIUM xvii 

LIST OF FIGURES 

3-1. Levels of Significant Exposure to Beryllium - Inhalation ................................ 41 
 

3-2. Levels of Significant Exposure to Beryllium - Oral .................................... 79 
 

3-3. Conceptual Representation of a Physiologically Based Pharmacokinetic (PBPK) Model
 

for a Hypothetical Chemical Substance ............................................ 104 
 

3-4. Relationship Between Urine Level of Beryllium and Air Concentration ................... 114 
 

3-5. Existing Information on Health Effects of Beryllium .................................. 124 
 

6-1. Frequency of NPL Sites With Beryllium Contamination ............................... 150 
 

BERYLLIUM xix 

LIST OF TABLES 

3-1. Levels of Significant Exposure to Beryllium - Inhalation ............................... 24 
 

3-2. Levels of Significant Exposure to Beryllium - Oral .................................... 75 
 

3-3. Levels of Significant Exposure to Beryllium - Dermal ................................. 91 
 

3-4. Genotoxicity of Beryllium and Its Compounds In Vitro ................................ 95 
 

3-5. Histologic Characteristics of Beryllium-induced Disease in Mice and Humans ............. 108 
 

3-6. Ongoing Studies on Beryllium ................................................... 135 
 

4-1. Chemical Identity of Beryllium and Beryllium Compounds ............................ 138 
 

4-2. Physical and Chemical Properties of Beryllium and Beryllium Compounds ................ 140 
 

5-1. Facilities that Produce, Process, or Use Beryllium .................................... 145 
 

5-2. Facilities that Produce, Process, or Use Beryllium Compounds .......................... 146 
 

6-1. Anthropogenic and Natural Emissions of Beryllium and Beryllium Compounds to the 

Atmosphere .................................................................. 153 
 

6-2. Releases to the Environment from Facilities that Produce, Process, or Use Beryllium ........ 154 
 

6-3. Releases to the Environment from Facilities that Produce, Process, or Use Beryllium
 

Compounds .................................................................. 155 
 

6-4. Precipitation of Beryllium Compounds in a Neutral (pH 6.5–9.5) Environment ............. 162 
 

6-5. Beryllium Content of Drinking Water ............................................. 167 
 

6-6. Beryllium Content of Various Fresh Foods ......................................... 170 
 

6-7. Beryllium Content of Various Fruits and Fruit Juices ................................. 172 
 

6-8. Ongoing Studies on Human Exposure to Beryllium ................................... 182 
 

7-1. Analytical Methods for Determining Beryllium in Biological Materials ................... 184 
 

7-2. Analytical Methods for Determining Beryllium in Environmental Samples ................ 187 
 

8-1. Regulations and Guidelines Applicable to Beryllium ................................. 195 
 

BERYLLIUM 1 

1. PUBLIC HEALTH STATEMENT 

This public health statement tells you about beryllium and the effects of exposure. 

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

the nation. These sites make up the National Priorities List (NPL) and are the sites targeted for 

long-term federal cleanup activities. Beryllium has been found in at least 535 of the 

1,613 current or former NPL sites. However, the total number of NPL sites evaluated for this 

substance is not known. As more sites are evaluated, the sites at which beryllium is found may 

increase. This information is important because exposure to this substance may harm you and 

because these sites may be sources of exposure. 

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 beryllium, 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 

it. 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 IS BERYLLIUM? 

Beryllium is an element that occurs naturally. It is present in a variety of materials, such as 

rocks, coal and oil, soil, and volcanic dust. Two kinds of mineral rocks, bertrandite and beryl, 

are mined commercially for the recovery of beryllium. Very pure gem-quality beryl is better 

known as either aquamarine (blue or blue-green) or emerald (green). Beryllium is the lightest 

metal. A key distinction among beryllium compounds is that some are soluble in water, but 

many are not. 
BERYLLIUM 2 

1. PUBLIC HEALTH STATEMENT 

Most of the beryllium ore that is mined is converted into alloys (mixtures of metals). Most of 

these alloys are used in making electrical and electronic parts or as construction materials for 

machinery and molds for plastics. Beryllium alloys are also used in automobiles, computers, 

sports equipment (such as golf clubs and bicycle frames), and dental bridges. Pure beryllium 

metal is used in nuclear weapons and reactors, aircraft and space vehicle structures, instruments, 

x-ray machines, and mirrors. Beryllium oxide is also made from beryllium ores and is used to 

make specialty ceramics for electrical and high-technology applications. More information on 

the chemical and physical properties, production, and uses of beryllium is found in Chapters 4, 5, 

and 6. 

1.2 WHAT HAPPENS TO BERYLLIUM WHEN IT ENTERS THE ENVIRONMENT? 

Beryllium enters the air, water, and soil as a result of natural and human activities. Emissions 

from burning coal and oil increase beryllium levels in the air. In air, beryllium compounds are 

present mostly as fine dust particles. The dust eventually settles over land and water. Rain and 

snow aid in removing beryllium from air. Extremely small beryllium particles may remain in the 

air for about 10 days. Beryllium enters waterways from the wearing away of rocks and soil. 

Most beryllium products of human origin that enter waterways come from industry discharges of 

waste water and from beryllium dust in the air from industrial activities settling over water. 

Most of the beryllium in water settles in the material on the bottom with sediment. Insoluble 

beryllium compounds remain in ocean water for a few hundred years before settling to the 

bottom of the ocean. Beryllium, as a chemical component, occurs naturally in soil; however, 

disposal of coal ash, incinerator ash, and industrial wastes may increase the amount of beryllium 

in soil. A major portion of beryllium in soil does not dissolve in water and remains bound to 

soil, so it is not likely to move deeper into the ground and enter groundwater. In the 

environment, chemical reactions can change the water-soluble beryllium compounds into 

insoluble forms. In some cases, water-insoluble beryllium compounds can change to soluble 

forms. Exposure to water-soluble beryllium compounds in the environment, in general, will 

pose a greater threat to human health than exposure to water-insoluble forms. 
BERYLLIUM 3 

1. PUBLIC HEALTH STATEMENT 

The amount of beryllium that has been measured in the air in different parts of the United States 

by EPA ranges from not detected to 2 millionths of a gram per cubic meter (g/m3). Very small 

dust particles of beryllium in the air fall out of the air onto surface water, plant surfaces, and soil 

either by themselves or when rain or snow falls. These beryllium particles eventually end up 

back in the soil or in the bottoms of lakes, rivers, and ponds, where they stay and mix with 

beryllium that is already there. 

Beryllium in water comes from different sources. Most of it comes from dissolving beryllium 

out of rocks and soil that water runs over and through. Only a very small part is from the settling 

of beryllium dust out of the air. Some beryllium is suspended in muddy-like (cloudy) water. 

EPA has found that the levels of beryllium in drinking water in different parts of the United 

States are extremely low in most cases, and that water containing beryllium at these commonly 

observed levels is safe to drink. Fish do not accumulate beryllium from water into their bodies 

to any great extent. Some fruits and vegetables such as garden peas, kidney beans, and pears 

may have above average levels of beryllium (see Chapter 6). Most of the beryllium that gets into 

livestock is eliminated quickly in urine and feces. 

Beryllium is found in soil in amounts that vary over a wide range, but the typical concentration is 

3 thousandths of a gram/kilogram (g/kg) of soil. Additional beryllium can be added by industrial 

activities. Soluble beryllium compounds can combine with other substances in the environment 

to form other beryllium compounds. Beryllium compounds may stay in the soil for thousands of 

years without moving downward into groundwater. In addition to the beryllium found naturally 

in minerals, beryllium metal and compounds that are left after humans mine and process the 

minerals can be released back into the environment as landfill waste. More information about 

the fate and movement of beryllium in the environment is found in Chapter 6. 
BERYLLIUM 4 

1. PUBLIC HEALTH STATEMENT 

1.3 HOW MIGHT I BE EXPOSED TO BERYLLIUM? 

You can be exposed to normal levels of beryllium by breathing air, eating food, or drinking 

water that contains beryllium. In the United States, the average concentration of beryllium in air 

is 0.03 nanograms (ng) (1 ng=1 billionth of a gram) in a cubic meter (ng/m3) of air. In U.S. 

cities, the average air concentration is higher, and its value is 0.2 ng in a cubic meter (m3

) of air. 

Cities have higher levels of beryllium in the air because beryllium is released from burning coal 

and fuel oil. The amount of beryllium that has been measured in drinking water in different parts 

of the United States by EPA is generally less than 2 trillionths of a gram for every liter of water. 

Beryllium was found in only 5% of 1,577 drinking water samples obtained throughout the 

United States. Of these positive samples, the average beryllium concentration was only 190 ng 

in a liter (L) of water. Beryllium, as a chemical component, is found naturally in some food. 

The concentration of beryllium in both raw carrots and field corn grown in the United States is 

less than 25 micrograms (μg) (1 μg=1 millionth of a gram) in a kilogram (kg) of the fresh 

vegetables. Thus, in comparison with other harmful elements, such as lead and chromium, to 

which we are (by necessity) exposed on a daily basis, beryllium exposure is not significant. 

In certain workplaces, you can be exposed to higher-than-normal levels of beryllium, mostly in 

the form of beryllium oxide and beryllium metal. Occupational exposure to beryllium occurs at 

places where the chemical is mined, processed, or converted into metal, alloys, and other 

chemicals. Workers engaged in machining metals containing beryllium, recycling beryllium 

from scrap alloys, or using beryllium products may also be exposed to higher levels of beryllium. 

The number of workers exposed to beryllium or beryllium compounds has been estimated to be 

21,000. 

As a member of the general public, you may be exposed to higher-than-normal levels of 

beryllium if you live near an industry that processes or uses beryllium. People who live near 

hazardous landfill sites that contain high concentrations of beryllium may also be exposed to 

higher-than-normal levels of beryllium. Beryllium, as a chemical component, occurs naturally in 

tobacco and may be inhaled from cigarette smoke. People who smoke may breathe higher-thannormal levels of beryllium than people who do not smoke. 
BERYLLIUM 5 

1. PUBLIC HEALTH STATEMENT 

Beryllium metal and metal alloys may be found in consumer products such as electronic devices 

(e.g., televisions, calculators, and personal computers) and special nonsparking tools. Direct 

contact with beryllium metal and metal alloys is not likely, since these materials are typically 

enclosed within a protected case that prevents exposure. No other consumer products or 

products used in crafts, hobbies, or cottage industries contain significant amounts of beryllium. 

It is therefore unlikely that beryllium present in consumer products poses any hazard. More 

information about beryllium exposure can be found in Chapter 6. 

1.4 HOW CAN BERYLLIUM ENTER AND LEAVE MY BODY? 

Beryllium can enter your body if you breathe air, eat food, or drink water containing it. 

Beryllium will not enter your body from skin contact with the metal unless the skin is scraped or 

cut and beryllium particles become imbedded in the wound. Only a small amount of beryllium 

may enter your body if your skin comes into contact with a beryllium salt dissolved in water. 

When you breathe air containing beryllium, beryllium particles can be deposited in the lungs. 

The beryllium that you breathe in slowly dissolves in the lungs and moves slowly into the 

bloodstream. Some of the beryllium deposited in the lungs can be moved to the mouth and then 

swallowed; the rest can remain in your lungs for a long time. If you eat food or drink water that 

contains beryllium, less than 1% passes from your stomach and intestines into the bloodstream. 

Therefore, most of the beryllium that you swallow leaves your body through the feces without 

entering the bloodstream. The small amount of beryllium that moves from the lungs, stomach, 

and intestines into the bloodstream is carried by the blood to the kidneys. Beryllium leaves the 

kidneys by the urine. Some beryllium can also be carried by the blood to the liver and bones 

where it may remain for long periods. If you swallow beryllium, beryllium leaves the body in a 

few days. However, if you inhale beryllium, it may take months to years before your body rids 

itself of beryllium. This is because it takes a long time before all the beryllium in the lungs 

enters the bloodstream. For more information, please read Chapter 3. 
BERYLLIUM 6 

1. PUBLIC HEALTH STATEMENT 

1.5 HOW CAN BERYLLIUM 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 wise 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. 

Beryllium is a metal that can be harmful when you breathe it. The effects depend on how much 

and how long you are exposed to it. When you breathe it in, beryllium can damage your lungs. 

When you breathe in large amounts of soluble beryllium compounds (greater than 1 mg 

beryllium per cubic meter of air, 1 mg/m3

), the lung damage resembles pneumonia with 

reddening and swelling of the lungs. This condition is called acute beryllium disease. The lung 

damage may heal if beryllium exposure is stopped. Human studies have shown that occupational 

and community ambient air standards were effective in eliminating most acute lung disease. 

Some people can become sensitive to beryllium. This is known as hypersensitivity or allergy. If 

you become sensitive (allergic) to beryllium, you may develop an immune or inflammatory 

reaction to small amounts of beryllium that do not cause effects in people who are not sensitive 

to beryllium. When this occurs, white cells accumulate around the beryllium and form a chronic 

inflammatory reaction called granulomas (granulomas are not tumors). This condition is called 

chronic beryllium disease (CBD). This disease can occur long after exposure (10–15 years) to 

small amounts of either soluble or insoluble forms of beryllium (greater than 0.0005 mg/m3

). If 

you have this disease, you may feel weak, tired, and have difficulty breathing. Some individuals 

that have CBD may experience anorexia, weight loss, and blueness of hands and feet. This 

disease could also lead to heart enlargement and heart disease in advanced cases. 
BERYLLIUM 7 

1. PUBLIC HEALTH STATEMENT 

Both the short-term, pneumonia-like disease and the chronic beryllium disease can be fatal. 

Exposure levels associated with acute or chronic beryllium disease are more 100,000 times 

higher than normal air levels of beryllium. Long periods of exposure to beryllium have been 

reported to cause cancer in laboratory animals. Some studies of workers reported an increased 

risk of lung cancer. The U.S. Department of Health and Human Services and the International 

Agency for Research on Cancer have determined that beryllium and beryllium compounds are 

human carcinogens. EPA has determined that beryllium is a probable human carcinogen. EPA 

has estimated that lifetime exposure to 0.00004 mg beryllium/m3

 can result in a one in a 

thousand chance of developing cancer. We do not know if breathing air, eating food, or drinking 

water that contains beryllium or having skin contact with beryllium has any effects on 

reproduction or causes birth defects in humans or animals. Swallowing beryllium has not been 

reported to cause effects in humans because very little beryllium can move from the stomach or 

intestines into the bloodstream. Ulcers have been seen in dogs ingesting soluble beryllium salts 

in the diet. Beryllium contact with skin that has been scraped or cut may cause rashes or ulcers. 

If you have developed an allergy to beryllium and have skin contact with it, you can get 

granulomas on the skin. These skin granulomas appear as a rash or as nodules. The skin 

granulomas are formed in the same way that lung granulomas are formed in sensitive people. 

For more information on how beryllium can affect your health, please read Chapter 3. 

1.6 HOW CAN BERYLLIUM AFFECT CHILDREN? 

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

to maturity at 18 years of age in humans. 

It is likely that the health effects seen in children exposed to beryllium will be similar to the 

effects seen in adults; chronic beryllium disease was found in a child living near a beryllium 

factory. We do not know whether children differ from adults in their susceptibility to beryllium. 

We do not know if exposure to beryllium will result in birth defects or other developmental 

effects in people. The studies on developmental effects in animals are not conclusive. We have 

no information to suggest that there are any differences between children and adults in terms of 
BERYLLIUM 8 

1. PUBLIC HEALTH STATEMENT 

how much beryllium will enter the body, where beryllium can be found in the body, and how fast 

beryllium will leave the body. It is likely that beryllium can be transferred from the mother to an 

infant in breast milk or that it can cross the placenta. 

1.7	 HOW CAN FAMILIES REDUCE THE RISK OF EXPOSURE TO BERYLLIUM? 

If your doctor finds that you have been exposed to significant amounts of beryllium, ask whether 

your children might also be exposed. Your doctor might need to ask your state health 

department to investigate. 

Higher-than-normal levels of beryllium may be in soil at hazardous waste sites. Some children 

eat a lot of dirt. You should prevent your children from eating dirt. Make sure they wash their 

hands frequently, and before eating. If you live near a hazardous waste site, discourage your 

children from putting their hands in their mouths or from engaging in other hand-to-mouth 

activities. Some children may be exposed to beryllium by contact with a family member who 

works in a facility using beryllium. If you work at a facility that uses beryllium, make sure you 

change your clothes and clean your hair and skin before leaving your job and returning home. 

Also, do not bring objects home such as works tools that may be contaminated with beryllium. 

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

EXPOSED TO BERYLLIUM? 

Beryllium can be measured in the urine and blood, but the amount of beryllium in the urine or 

blood may not reflect the amount to which you were exposed. The measurement of beryllium in 

urine and blood may not determine how recently you were exposed. Small amounts of human 

lung and skin can be removed from the body and examined to determine whether beryllium is 

present in these tissues. These tests can be done in a doctor's office or in a hospital. While high 

levels of beryllium in urine, blood, or tissues indicate that you were exposed to an excessive 

amount of beryllium, low levels of beryllium do not necessarily mean that you were not exposed 

to an excessive amount. A blood test called the beryllium lymphocyte proliferation test (BeLPT) 
BERYLLIUM 9 

1. PUBLIC HEALTH STATEMENT 

can determine if you have become sensitive to beryllium and may have chronic beryllium 

disease. For more information, please read Chapters 3 and 7. 

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). 

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; then they are 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 beryllium include the following: 

OSHA has set a limit of 2 μg beryllium/m3

 of workroom air for an 8-hour work shift. NIOSH 

recommends a standard for occupational exposure of 0.5 μg beryllium/m3

 of workroom air 

during an 8-hour shift to protect workers from the increased cancer risk associated with 

beryllium exposure. EPA restricts the amount of beryllium released into the air to 0.01 μg 

beryllium/m3

 of air, averaged over a 30-day period. The Department of Energy (DOE) has 

developed a program to reduce beryllium exposure in workers at DOE facilities. EPA has set a 
BERYLLIUM 10 

1. PUBLIC HEALTH STATEMENT 

maximum allowable amount of 0.004 mg/L beryllium in drinking water. For more information, 

please read Chapter 8. 

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 

Agency for Toxic Substances and Disease Registry
 

Division of Toxicology
 

1600 Clifton Road NE, Mailstop E-29
 

Atlanta, GA 30333
 

Web site: http://www.atsdr.cdc.gov
 

* Information line and technical assistance 

Phone: 1-888-42-ATSDR (1-888-422-8737)
 

Fax: 1-404-498-0057
 

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. 

* To order toxicological profiles, contact 

National Technical Information Service
 

5285 Port Royal Road
 

Springfield, VA 22161
 

Phone: 1-800-553-6847 or 1-703-605-6000
 
BERYLLIUM 11 

2. RELEVANCE TO PUBLIC HEALTH
 

2.1	 BACKGROUND AND ENVIRONMENTAL EXPOSURES TO BERYLLIUM IN THE 

UNITED STATES 

Beryllium is an extremely lightweight metal that occurs naturally in rocks, coal, soil, and volcanic dust. 

Commercially, bertrandite and beryl ore are mined for the recovery of beryllium. Because beryllium is 

one of the lightest metal and is very rigid, it has many uses in the electronics, aerospace, and defense 

industries. Beryllium is released into the atmosphere by windblown dust, volcanic particles, and the 

combustion of coal and fuel oil. Beryllium particulates in the atmosphere will settle out or be removed by 

precipitation. The annual average concentration of beryllium in ambient air in the United States is 

typically below the detection limit of 0.03 ng/m3

. Beryllium concentration in urban air is usually higher 

due primarily to burning of coal and fuel oil; for example, the annual average concentrations in 

1982–1992 ranged from 0.02 to 0.2 ng/m3

 in Detroit, Michigan. Beryllium can be released into 

waterways by the weathering of soil and rocks. Beryllium entering surface water bodies and soil will be 

retained in the sediment and soil and will be generally immobile. The average concentration of beryllium 

in drinking water samples that were found to contain it was 190 ng/L. The mean concentration of 

beryllium in soil in the United States is 0.6 mg/kg. 

Human exposure to beryllium and its compounds occurs primarily in the workplace. People who work in 

beryllium manufacturing, fabricating, and reclaiming industries have a greater probability of inhalation 

exposure than non-occupational groups. The general population can be exposed to trace amounts of 

beryllium through inhalation of air, consumption of food and water, and skin contact with air, water, or 

soil that contains beryllium. Individuals living near sources of beryllium emissions are likely to be 

exposed to higher levels of beryllium than the general population. Beryllium has been identified in at 

least 535 of the 1,613 hazardous waste sites that have been proposed for inclusion on the EPA NPL. 

2.2	 SUMMARY OF HEALTH EFFECTS 

The general population can be exposed to beryllium via inhalation, oral, and dermal routes of exposure. 

The inhalation route is of greatest concern for systemic effects because beryllium and its compounds are 

poorly absorbed after oral and dermal exposure. The respiratory tract in humans and animals is the 

primary target of beryllium toxicity following inhalation exposure. Occupational exposure to high 

concentrations of soluble beryllium compounds can result in acute beryllium disease, while exposure to 
BERYLLIUM 12 

2. RELEVANCE TO PUBLIC HEALTH 

relatively low concentrations ($0.5 μg/m3) of soluble or insoluble beryllium compounds can result in 

chronic beryllium disease. Acute beryllium disease is characterized by inflammation of the respiratory 

tract tissues and is usually resolved within several months of exposure termination. In contrast, chronic 

beryllium disease is an immune response to beryllium and is only observed in individuals who are 

sensitized to beryllium (usually <15% of an exposed population). Other systemic effects that have been 

observed in individuals with severe cases of chronic beryllium disease include damage to the right heart 

ventricle, hepatic necrosis, kidney stones, and weight loss; these effects are probably secondary to chronic 

beryllium disease rather than a direct effect on the tissues. 

As with inhalation exposure, dermal contact with beryllium can result in an allergic response, typically 

skin granulomas, in certain individuals. Dermatitis, which may be due to direct irritation rather than an 

immune response, has also been observed in workers exposed to high concentrations of airborne 

beryllium. 

Unlike inhalation and dermal exposure routes, the primary effects observed after oral exposure is not an 

immune response to beryllium. The most sensitive effects appear to be ulcerative gastrointestinal lesions 

in dogs and beryllium rickets in rats exposed to beryllium carbonate; no reliable human oral exposure 

data were identified. The beryllium rickets are not due to a direct effect on bone; they are secondary to 

phosphorus deficiency. Beryllium in the gut binds to soluble phosphorus compounds to form insoluble 

beryllium phosphate, thus decreasing the amount of soluble phosphorus compounds available for 

absorption. 

The available data on the potential of beryllium to induce reproductive and/or developmental effects are 

inconclusive. The data come from several animal studies; no reliable human data were located. No 

histological alterations have been observed in reproductive tissues of animals orally exposed to beryllium 

sulfate and no alterations in fertility were observed in dogs exposed to beryllium sulfate in the diet. 

Similarly, no reproductive effects were observed in rats exposed to beryllium oxide via intratracheal 

injection. Some developmental effects (fetal mortality, decreased fetal body weight, increased prevalence 

of internal abnormalities) were observed in the offspring of rats receiving a single intratracheal injection 

of beryllium oxide or beryllium chloride. No developmental effects were observed in the offspring of 

dogs orally exposed to beryllium sulfate, although the study is limited because cannibalized and stillborn 

animals were not examined. Human and animal data provide evidence that inhaled beryllium is a human 

lung carcinogen; oral data are inadequate for the assessment of carcinogenic potential. 
 

BERYLLIUM 13 

2. RELEVANCE TO PUBLIC HEALTH 

Thus, the primary adverse health of effects of beryllium are respiratory effects and lung cancer following 

inhalation exposure, gastrointestinal effects following oral exposure, and skin effects following dermal 

exposure; these effects are discussed in greater detail below. The reader is referred to Section 3.2, 

Discussion of Health Effects by Route of Exposure, for additional information on other health effects. 

Respiratory Effects. The toxicity of beryllium to the respiratory tract is usually manifested in one of 

two syndromes: acute beryllium disease and chronic beryllium disease. Acute beryllium disease is 

usually observed at relatively high beryllium exposure levels, has a short period of induction, and is 

usually resolved within a couple of months of exposure termination. It is believed to be an inflammatory 

response to beryllium and most regions of the respiratory tract are affected; some reported symptoms 

include nasopharyngitis, shortness of breath, labored breathing, and chemical pneumonitis. 

Chronic beryllium disease is a systemic granulomatous disorder that predominantly affects the lungs. In 

general, the occurrence of this disease has been confined to workers exposed to beryllium metal and to 

less soluble beryllium compounds, such as beryllium oxide. However, there have been cases among 

residents living near beryllium manufacturing facilities and in families of workers who wore 

contaminated clothing at home. Chronic beryllium disease is caused by an immune reaction to the 

inhaled beryllium that is deposited in lung airspaces and retained for a prolonged period. In certain 

individuals who become sensitized to beryllium, the beryllium in the lungs acts as a hapten, binds to 

protein/peptides in the lungs, and elicits a proliferation of T lymphocytes, a release of inflammatory 

mediators, and an accumulation of inflammatory cells in the lungs. This results in the formation of 

noncaseating granuloma, the accumulation of mononuclear cell infiltrates, and the development of 

fibrosis. Susceptibility to chronic beryllium disease is believed to have a genetic component. The human 

leukocyte antigen (HLA) class II marker, HLA-DPB1 Glu69, has been found in a large number of 

individuals with chronic beryllium disease. 

When chronic beryllium disease was first recognized, affected individuals had a number of signs and 

symptoms including weight loss, dyspnea, cough, chest pain, fatigue, and cor pulmonale (hypertrophy of 

the right heart ventricle). Impaired lung function was detected in most of the affected individuals. The 

typical lung function abnormalities were decreased vital capacity and total lung capacity and/or reduction 

in diffusing capacity for carbon monoxide (DLCO). It is likely that these cases of chronic beryllium 

disease were diagnosed at a late stage. Technological advances in the development of methods to detect 

chronic beryllium disease, in particular the beryllium lymphocyte proliferation test (BeLPT) and fiber 

optic bronchoscopy and transbronchial biopsy methods, now allows for the early detection of the disease. 
BERYLLIUM 14 

2. RELEVANCE TO PUBLIC HEALTH 

Chronic beryllium disease can be classified into three stages: beryllium sensitization, subclinical chronic 

beryllium disease, and clinical chronic beryllium disease. Beryllium sensitization, usually diagnosed as 

consistently abnormal BeLPT results, can progress to chronic beryllium disease, but not all sensitized 

individuals develop chronic beryllium disease. Individuals with subclinical chronic beryllium disease are 

sensitized to beryllium and have histological evidence of lung granulomas, but no clinical signs. 

Although no clinical signs are observed, there is evidence to suggest that there may be some impairment 

of lung function. Slight alterations in lung function during exercise were observed in approximately 60% 

of individuals with subclinical chronic beryllium disease, no other consistent alterations in lung function 

were found. Individuals with clinical chronic beryllium disease are beryllium sensitized, and have 

histological evidence of lung granulomas and respiratory symptoms, changes on chest radiographs, and/or 

altered lung function. 

A number of large-scale screening studies have examined beryllium workers and found beryllium 

sensitization rates of 1–15% in workers involved in the production of beryllia ceramics and nuclear 

weapons. More than half of the beryllium sensitized workers were diagnosed with chronic beryllium 

disease. Several studies attempted to establish associations between beryllium sensitization and/or 

chronic beryllium disease and mean, cumulative, and peak exposure levels and duration of employment. 

In general, no consistent associations were found. Although the data are insufficient for establishment of 

concentration-response relationships, the available occupation exposure studies do provide exposure 

levels that may result in beryllium sensitization. Beryllium sensitization and/or chronic beryllium disease 

have been detected at exposure levels of $0.5 μg/m3

. Respiratory disease is not likely to occur from 

exposure to beryllium levels in the general environment because ambient air levels of beryllium 

(0.03–0.2 ng beryllium/m3

) are very low. 

Gastrointestinal Effects. No human data were located regarding gastrointestinal effects following 

exposure to beryllium. In dogs exposed to beryllium sulfate in the diet for 143–172 weeks, extensive 

ulcerative and inflammatory lesions were observed in the small intestine, stomach, and large intestine; the 

small intestine was the most severely affected. No gastrointestinal tract lesions were observed in rats 

exposed to similar concentrations of beryllium sulfate in the diet for 2 years. One possible explanation 

for the apparent species difference is the manner in which rats and dogs consumed the berylliumcontaining diet. The dogs only had access to the diet for 1 hour/day, in contrast to the rats with unlimited 

access to the diet. Thus, immediately after eating, the dogs had a higher concentration of beryllium in the 

gut than the rats that ate small amounts of food throughout the day. 
BERYLLIUM 15 

2. RELEVANCE TO PUBLIC HEALTH 

Dermal Effects. Two types of dermal effects have been observed in beryllium exposed workers: an 

inflammatory reaction and an immune reaction. Edematous papulovesicular dermatitis was observed in 

workers exposed to airborne beryllium sulfate, beryllium fluoride, or beryllium oxyfluoride; this is likely 

an inflammatory response to beryllium. Beryllium exposure may also cause a delayed, hypersensitive 

reaction in the skin. Biopsied skin granulomas from beryllium workers had the same mononuclear 

infiltrates as detected in the lungs. Sensitized guinea pigs also developed granulomatous lesions and 

other delayed hypersensitive reactions following dermal exposure to beryllium sulfate, beryllium fluoride, 

beryllium oxide, or beryllium chloride. 

Cancer. A number of epidemiology studies have been conducted to assess the carcinogenic potential 

of beryllium. Increased incidences of lung cancer deaths were reported in retrospective cohort mortality 

studies of workers at beryllium extraction, processing, and fabrication facilities. Increased lung cancer 

mortality was also seen in entrants to the Beryllium Case Registry. No correlation between the incidence 

of lung cancer deaths and exposure has been established because historical exposure levels were not 

reported. A positive association between length of latency and lung cancer deaths was found, with the 

highest cancer risks among workers with a latency of $25 years. Significant increases in the occurrence 

of lung cancer has also been observed in rats and monkeys exposed to beryllium. 

The National Toxicology Program lists beryllium and certain beryllium compounds (beryllium-aluminum 

alloy, beryllium chloride, beryllium fluoride, beryllium hydroxide, beryllium oxide, beryllium phosphate, 

beryllium sulfate, beryllium zinc silicate, and beryl ore) as human carcinogens. Based on sufficient 

evidence for carcinogenicity in humans and animals, the International Agency for Research on Cancer has 

classified beryllium and beryllium compounds in Group 1, carcinogenic to humans. In contrast, the EPA 

concluded that the human data only provided limited evidence and classified inhaled beryllium in Group 

B1, a probable human carcinogen. 

No human studies investigating the carcinogenicity of ingested beryllium were located. Animal studies 

have not found significant associations between ingestion of beryllium in the diet and drinking water and 

increased incidence of neoplasms in rats, mice, or dogs. It should be noted that no toxic effects were 

observed in rat and mouse chronic-duration studies tested at low doses, and the duration of the dog study 

was too short to be predictive of late-term cancer. The EPA concluded that the human carcinogenic 

potential of ingested beryllium cannot be determined. 
BERYLLIUM 16 

2. RELEVANCE TO PUBLIC HEALTH 

2.3 MINIMAL RISK LEVELS 

Inhalation MRLs 

The available human and animal data clearly identify the respiratory tract as the critical target of 

beryllium toxicity following inhalation exposure. In humans, symptoms of acute beryllium disease (e.g., 

nasopharyngitis, pneumonia) have been reported in workers exposed to high concentrations of soluble 

beryllium compounds (Eisenbud et al. 1948a; VanOrdstrand et al. 1945). Longer-term exposure to 

relatively low concentrations of beryllium can result in chronic beryllium disease (Cotes et al. 1983; 

Cullen et al. 1987; Eisenbud et al. 1949). More recent studies are able to detect subclinical chronic 

beryllium disease and beryllium sensitization (Deubner et al. 2001; Henneberger et al. 2001; Kelleher et 

al. 2001; Kreiss et al. 1993a, 1996, 1997; Newman et al. 2001; Stange et al. 1996b, 2001; Viet et al. 

2000). There is evidence to suggest that the occurrence of chronic beryllium disease is not related to 

duration of exposure, and can have a long latency period. Very few studies assessing the occurrence of 

chronic beryllium disease also measured airborne beryllium levels. Eisenbud et al. (1949) found no cases 

of chronic beryllium disease in residents living at least 0.75 miles away from a beryllium manufacturing 

facility. The airborne beryllium concentration at this distance was estimated to range from 0.01 to 0.1 μg 

beryllium/m3

. Studies by Cullen et al. (1987), Kreiss et al. (1996), and Stange et al. (1996b) reported 

chronic beryllium disease (and/or beryllium sensitization) in workers exposed to average beryllium 

concentrations of 0.52, 0.55, or 1.04 μg beryllium/m3

, respectively. 

Respiratory tract effects have also been observed in animals exposed to airborne beryllium. Emphysema, 

pneumonitis, and lung granulomas are the most commonly reported effects following acute-, 

intermediate-, and chronic-duration exposure (Haley et al. 1989; Hall et al. 1950; Robinson et al. 1968; 

Schepers et al. 1957; Sendelbach et al. 1986; Stokinger et al. 1950; Wagner et al. 1969). In general, the 

animal studies have not identified a reliable no-observed-adverse-effect level (NOAEL) for respiratory 

effects, and the lowest-observed-adverse-effect levels (LOAELs) are several orders of magnitude higher 

than the LOAEL identified in the Kreiss et al. (1996) occupational exposure study. 

Although the critical target of beryllium toxicity has been identified, the available database does not 

support derivation of acute-, intermediate-, or chronic-duration inhalation MRLs. As discussed in 

Section 3.4.3, an animal model that mimics all aspects of chronic beryllium disease has not been 

identified; thus, it is inappropriate to derive inhalation MRLs from the animal data. No human acute- or 

intermediate-duration studies that identify a NOAEL or LOAEL for respiratory effects were located. The 
17 

C

BERYLLIUM 

2. RELEVANCE TO PUBLIC HEALTH 

Eisenbud et al. (1949) study, found no cases of chronic beryllium disease among community residents 

chronically exposed to 0.01–0.1 μg beryllium/m3

. This study was not selected as the basis of a chronicduration MRL because it utilized relatively insensitive methods to detect chronic beryllium disease; in 

particular, it is not known if residents exposed to 0.01 μg beryllium/m3

 would test positive for beryllium 

sensitization or subclinical chronic beryllium disease. The LOAELs identified in the Cullen et al. (1987), 

Kreiss et al. (1996), and Stange et al. (1996b) studies cannot be used to derive a chronic MRL because the 

observed effects were classified as serious health effects. 

Oral MRLs 

The only available data on the acute-duration toxicity of ingested beryllium are from lethality studies in 

rats and mice. Thus, an acute-duration oral MRL cannot be derived. The available data from 

intermediate-duration studies have identified rickets (Guyatt et al. 1933; Jacobson 1933; Kay and Skill 

1934) as a critical target of beryllium toxicity. The rickets do not appear to be due to a direct effect of 

beryllium on the bone. Rather, the rickets are due to a phosphorus deficiency, which results from the 

binding of beryllium to dietary phosphorus in the gut. Additionally, these effects have only been 

observed following exposure to beryllium carbonate. Thus, the available data are inadequate for 

derivation of an intermediate-duration oral MRL. 

An MRL of 0.002 mg beryllium/kg/day has been derived for chronic-duration oral exposure 

(>365 days) to beryllium. 

A chronic-duration oral MRL of 0.002 mg beryllium/kg/day was derived for beryllium. The MRL is 

based on a chronic dog feeding study in which groups of five male and five female dogs were exposed to 

beryllium sulfate in the diet for 143–172 weeks (Morgareidge et al. 1976). Ulcerative lesions of the small 

intestine were observed in 9 of 10 dogs exposed to the highest dose (500 ppm; 12 and 17 mg 

beryllium/kg/day for the males and females, respectively); similar lesions were also observed in 1 of 

10 dogs exposed to 50 ppm (1 mg beryllium/kg/day). No gastrointestinal effects were observed at the 

lower dose levels. Other effects observed in the 500 ppm group included erythroid hyperplasia of the 

bone marrow, slight anemia, bile stasis and vasculitis in the liver, and acute inflammation of the lymph 

nodes; these effects were considered secondary to the gastrointestinal hemorrhages and a likely systemic 

bacterial invasion through the damaged intestinal mucosa. The 500 ppm test dose was discontinued after 

33 weeks due to high mortality and morbidity. The MRL was derived using a benchmark dose method, 

which involves fitting mathematical models to the dose-response data for the ulcerative lesions of the 

small intestine. For this analysis, the incidence data for the male and female dogs were combined and the 
BERYLLIUM 18 

2. RELEVANCE TO PUBLIC HEALTH 

calculated doses for the males and females were averaged. A benchmark dose (defined as the 95% lower 

confidence limit of the dose corresponding to a 10% increase in the incidence of small intestine lesions 

compared to controls) of 0.56 mg beryllium/kg/day was estimated using a probit model. The benchmark 

dose was divided by an uncertainty factor of 100 (10 for extrapolation from animals to humans and 10 for 

human variability) and a modifying factor of 3 (to account for the lack of a study that supports the 

gastrointestinal effects found in the Morgareidge et al. [1976] dog study and the uncertainty as to whether 

the benchmark dose level is the NOAEL). 
BERYLLIUM 19 

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 beryllium. 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 

lowest-observed-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 

"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 
BERYLLIUM 20 

3. HEALTH EFFECTS 

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 (LOAEL) 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. 

Levels of exposure associated with carcinogenic effects (Cancer Effect Levels, CELs) of beryllium are 

indicated in Table 3-1 and Figure 3-1. Because cancer effects could occur at lower exposure levels, 

Figure 3-1 also shows a range for the upper bound of estimated excess risks, ranging from a risk of 1 in 

10,000 to 1 in 10,000,000 (10-4 to 10-7), as developed by EPA. 

Estimates of exposure levels posing minimal risk to humans (or MRLs) have been made for beryllium. 

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. 
BERYLLIUM 21 

3. HEALTH EFFECTS 

Beryllium is a lightweight metal that has many uses, including some in the aerospace industry. Beryllium 

is present in the earth as beryllium ores, such as beryl and bertrandite. Most beryllium compounds are 

poorly soluble in water. The most common compound is beryllium oxide, the solubility of which 

decreases in water as the temperature at which it is calcined increases. Beryllium carbonate and 

hydroxide are also practically insoluble in water. Beryllium chloride, fluoride, nitrate, phosphate, and 

sulfate (tetrahydrate) are all soluble in water. Beryllium carbonate, sulfate (tetrahydrate), and hydroxide 

are formed during the processing of beryllium containing ores into beryllium metal. Beryllium nitrate is 

used as a hardening agent for mantles on gas lanterns. Beryllium phosphate has no commercial uses. As 

seen in the discussions below, the solubility of beryllium compounds significantly impacts in the 

manifestation of toxic effects. 

3.2.1 Inhalation Exposure 

Most of the information regarding adverse effects in humans after inhalation exposure to beryllium or its 

compounds is available from studies of occupational exposure. In 1952, a Beryllium Case Registry 

(BCR) was established to provide a central source for cases of diagnosed beryllium poisoning (acute 

berylliosis or chronic beryllium disease). The criteria for entry in the BCR included either documented 

past exposure to beryllium or the presence of beryllium in lung tissue as well as clinical evidence of 

beryllium disease. Dose-response relationships are difficult to establish in the case of occupational 

exposure because reported workroom beryllium levels have generally ranged widely from <0.002 to 

1.0 mg beryllium/m3

, depending on when the measurements were made. The higher beryllium levels 

generally have occurred in the past; improvements in industrial hygiene over the last 30–40 years have 

effectively reduced workroom beryllium levels. Numerous studies provide concentration-response 

relationships for several end points in experimental animals. However, as discussed in Section 3.5.3, an 

animal model has not been identified for the most sensitive health effect, chronic beryllium disease. 

3.2.1.1 Death 

A number of retrospective cohort studies were conducted from data taken from the Beryllium Case 

Registry. The mortality rate among employees who worked at a major beryllium extraction, processing, 

and fabricating facility between 1942 and 1968 was higher than the national average, with respect to 

cardiovascular and pulmonary diseases (Wagoner et al. 1980). The incidence of death due to 

nonneoplastic respiratory disease was higher among employees who remained in the industry for <5 years 

after initial exposure and were exposed prior to 1950 when strict exposure controls were initiated. 
BERYLLIUM 22 

3. HEALTH EFFECTS 

Another retrospective cohort study of workers exposed to beryllium during 1952–1975 indicates that the 

overall mortality rates were significantly higher compared to the U.S. general mortality rate (Infante et al. 

1980). The incidence of death due to nonneoplastic respiratory disease was significantly higher in 

workers exposed for $15 years and who developed acute respiratory disease. However, in workers with 

chronic respiratory disease, the excess number of deaths was not related to the number of years since 

exposure. According to case histories of 3 men and 14 women employed in the beryllium industry for an 

average of 17 months, 6 of the women died from pulmonary or cardiovascular disease (Hardy and 

Tabershaw 1946). Most of the workers reported having shortness of breath, general weakness (fatigue), 

and weight loss. Autopsies revealed granulomatous disease, lung fibrosis, and heart enlargement. These 

were the first reported cases of chronic beryllium disease. 

As discussed in Section 3.2.1.2 under Respiratory Effects, exposure to beryllium can result in two types 

of nonneoplastic respiratory disease, acute beryllium disease and chronic beryllium disease. Both forms 

can be fatal. Ten fatalities occurred among 93 cases of acute beryllium pneumonitis that were 

documented in two beryllium refineries prior to 1950 (American College of Chest Physicians 1965). 

Autopsy of six of the cases revealed that the death occurred only in people with fulminating disease and 

resulted from massive pulmonary edema. The survival of workers diagnosed with chronic beryllium 

disease appears to be related to their pulmonary pathology. Patients with well-formed granulomas but 

with slight or absent interstitial cellular infiltration appeared to have a higher rate of survival than patients 

with few or absent granulomas, but with moderate to marked interstitial cellular infiltration (Freiman and 

Hardy 1970). 

There are several studies regarding death in animals after acute inhalation exposure to beryllium 

compounds. Exposure to 31 mg beryllium/m3

 as beryllium oxide caused death in 2 of 20 rats (Hall et al. 

1950). A 50-minute exposure to an aerosol of beryllium metal at 0.8 mg beryllium/m3

 resulted in the 

death of 20 of 74 rats 12–15 days after exposure (Haley et al. 1990). Upon necropsy, the rats had 

hemorrhagic lungs. All rats exposed to 4.3 mg beryllium/m3

 (Stokinger et al. 1950) or 2.59 mg 

beryllium/m3

 (Sendelbach and Witschi 1987a) as beryllium sulfate died by day 14 or 18, respectively. 

Three of 10 guinea pigs and 2 of 10 hamsters died when exposed to 4.3 mg beryllium/m3

 as beryllium 

sulfate for 14 days (Stokinger et al. 1950). All monkeys exposed to $13 mg beryllium/m3

 as beryllium 

hydrogen phosphate died after 8–10 days of exposure (Schepers 1964). Two of four monkeys exposed to 

0.184 mg beryllium/m3

 as beryllium fluoride died after 7–17 days of exposure. Only one of four 

monkeys died after 7 days of exposure to 0.198 mg beryllium/m3

 as beryllium sulfate. 
BERYLLIUM 23 

3. HEALTH EFFECTS 

The differences observed in the lethality values for certain beryllium compounds are primarily due to 

their various solubilities. Beryllium oxide was less toxic than beryllium sulfate, due to its relative 

insolubility in the lung. Based on limited comparisons among compounds and species, rats and monkeys 

appear to be more sensitive than hamsters and guinea pigs. 

Exposure to 0.43 mg beryllium/m3 as beryllium sulfate for #100 days caused death in 23 of 47 rats 

(Stokinger et al. 1950). Death was reported in 15 of 23 rats exposed to 30 mg beryllium/m3

 as beryllium 

oxide for 15 days (Hall et al. 1950). When rats, hamsters, and monkeys were exposed to 0.62 mg 

beryllium/m3

 as beryl or 0.21 mg beryllium/m3 as bertrandite ore for 6 months, 13, 25, and 11% died, 

respectively (Wagner et al. 1969). Signs of toxicity included respiratory distress, anemia, and body 

weight depression. One of five cats and 2 of 34 guinea pigs died when exposed to 0.43 mg beryllium/m3 

as beryllium sulfate for #100 days (Stokinger et al. 1950). Increased mortality was observed in mice, 

dogs, hamsters, and goats exposed to 2.0 mg beryllium/m3

 as beryllium sulfate for #51 days. The one 

monkey similarly exposed also died. 

Chronic exposure to 0.034 mg beryllium/m3

 as beryllium sulfate for 72 weeks did not increase mortality 

among male rats; however, the mortality rate among exposed females was $4 times that of controls 

(Reeves et al. 1967). This indicates that female rats may be more sensitive than male rats to chronic 

inhalation exposure to beryllium. 

The LC50 values and concentrations associated with increased mortality in each species and duration 

category are recorded in Table 3-1 and plotted in Figure 3-1. 

3.2.1.2 Systemic Effects 

No studies were located regarding gastrointestinal or musculoskeletal effects in humans or animals after 

inhalation exposure to beryllium or its compounds. The respiratory, cardiovascular, hematological, 

hepatic, renal, and dermal, and ocular effects observed in humans or animals after inhalation exposure to 

beryllium and its compounds are discussed below. The highest NOAEL values and all reliable LOAEL 
Table 3-1 Levels of Significant Exposure to Beryllium - Inhalation 

Exposure/ LOAEL 

Duration/ 

a NOEL Less Serious Serious Reference Key to Species Frequency 

(mglm3) Chemical Form figure (Strain) (Specific Route) System (mglm3) (mglm3) 

ACUTE EXPOSURE 

Death 

1 Monkey 7-17 d 6hrld Schepers 1964 

0.184 (2/4 died) 

(Macacus) BeF2 

2 Monkey 8-10 d 6hdd Schepers 1964 

13 (414 died) 

(Macacus) BeHP04 

3 Monkey 7d6hrld Schepers 1964 0.198 (114 died) 

(Macacus) BeS04 

w 

I 

4 Rat 50 rnin Haley et al. 1990 rn 

0.8 (20174 died) 2 

(Fischer- 344) Be metal i

I 

5 Rat 10 d 5dlwk 6hrld Hall et al. 1950 

31 (2120 died) (Wistar) Be0 

6 Rat 14 d 2hrld Sendelbach and Witschi 1987 

2.59 (20/20 died) (Fischer- 344) BeS04 

7 Rat 14 d Sdlwk Ghrld Stokinger et al. 1950 4.3 (10110 died) 

(NS) BeS04 

8 Gn Pig 14 d 5dlwk 6hrld Stokinger et al. 1950 

4.3 (3/10 died) 

(NS) BeS04 

9 Hamster 14 d 5dlwk 6hr/d Stokinger et al. 1950 4.3 (Z10 died) 

(NS) BeS04 
Key to figure 

a Species

(Strain) 

Exposure1 

Duration1 

Frequency (Specific Route) 

Table 3-1 Levels of Significant Exposure to Beryllium -

LOAEL 

System (mglm3) (mglm3) 

NOAEL Less Serious 

Inhalation 

(mglm 3) 

Serious 

(continued) 

Chemical Form 

Reference 

m 

7J 

rn 

10 

ACUTE EXPOSURE 

Systemic 

Monkey 8-10 d Ghrld 

(Macacus) Resp 13 (emphysema) Schepers 1964 

BeHP04 

Cardio 13 (enlarged heart) 

Hepatic 13 (hepatocyte degeneration) 

Renal 13 97 (degenerationof the nephrons) 

11 Monkey 

(Macacus) 

7-1 8 d 6hrId 

Endocr 

Bd Wt 

Resp 

Cardio 

13 

0.184 

(hypoplasiaof the adrenal 

gland) 

(enlarged heart) 

13 

0.184 

(severe weight loss, 8-34%) 

(emphysema) Schepers 1964 

BeF2 

w 

I 

rn

5

I 

rn 

-n 

n 

m

s 

(n 

Hepatic 0.1 84 (hepatocellular degeneration) 

Renal 0.184 (degenerationof the nephrons) 

Endocr 0.184 (adrenal hypotrophy) 

Bd Wt 0.184 (19-23% weight loss) 
m Table 3-1 Levels of Significant Exposure to Beryllium - Inhalation (continued) rn 

2 Exposure1 LOAEL II-

- Duration1 C

a Serious Reference z NOAEL Less Serious 

Chemical Form

Key to Species Frequency 

figure (Strain) (Specific Route) System (mglm3) (mglm3) (mglm3) 

ACUTE EXPOSURE 

Schepers 1964 12 Monkey 7 d 6hrld Resp 0.198 (emphysema)

(Macacus) BeS04 

Cardio 0.198 (enlarged heart) 

Hepatic 0.198 

Renal 0.198 (glornerular degeneration) 

Bd Wt 0.198 (24% average weight loss) 

u 

13 Rat 50 min Haley et al. 1990 

Resp 0.8 (acute pneumonitis progressing 

(Fischer- 344) to chronic inflammation and Be metal i

I necrosis) 

Hall et al. 1950 

Resp 31

14 Rat 10 d 5dlwk Ghrld 

(Wistar) Be0 

Hernato 31 

Musclskel 31 

Hepatic 31 

Renal 31 

Other 31 

15 Rat 1 hr Hart et al. 1984 

Resp 0.447 (lung inflammation) (Fischer- 344) Be0 

N 

m 
Table 3-1 Levels of Significant Exposure to Beryllium - Inhalation (continued) ~~ ~ ~ 

Exposure1 LOAEL 

Duration/ 

a NOAEL Less Serious Serious Reference Key to Species Frequency 

Chemical Form figure (Strain) (Specific Route) System (mglm3) (mglm3) (mdm3) 

ACUTE EXPOSURE 

16 Rat 1 hr Sendelbach and Witschi 1987 

Resp 7 (increased lactic (Fischer- 344) dehydrogenase and alkaline BeS04

phosphatase in bronchoalveolar 

lavage fluid) 

17 Rat 1 hr Sendelbach et al. 1986 

Resp 13 (pneurnonitis) (Fischer- 344) BeS04 

18 Rat 1hr Sendelbach et al. 1989 

Resp 4.05 (pneurnonitis) w 

(Fischer- 344) BeS04 I 

rn

F

-I 

19 Mouse Ihr Sendelbach and Witschi 1987 I Resp 7.2 (increased lactic rn (BALBlc) BeS04 n 

n dehydrogenase and alkaline 

phosphatase in bronchoalveolar rn 

lavage fluid) 

20 Mouse 1hr Sendelbach et al. 1986 

Resp 13 (lung inflammation) (BALBlc) BeS04 

21 Mouse 14 d 5dlwk 6hrId Stokinger et al. 1950 

Bd Wt 4.3 (13% body weight loss) (NS) BeS04 

22 Gn Pig 10 d 5dlwk 6hrld Hall et al. 1950 

Resp 31 (English) Be0 

Hepatic 31 

Renal 31 

Bd Wt 31 
C 

m Table 3-1 Levels of Significant Exaosure to Bervllium - Inhalation (continued) rn 

;D 

LOAEL $ Exposure/ r 

Duration1 Reference 

a ~ z

Key NOEL Less Serious Serious to Species Frequency Chemical Form figure (Strain) (Specific Route) System (mglm3) (mglm3) (mglm3) 

ACUTE EXPOSURE 

23 Dog 

(Beagle) 

Id Resp 10 (granulomas in lung) Haley et al. 1989 

Be0 

24 Dog 

(Beagle) 

20 min Resp 115 (granulomatous foci, 

inflammationof the lung) 

Robinson et al. 1968 

BeF2, Be0 BeCI2 

Bd Wt 115 (transient anorexia, weight loss) 

25 Rabbit 

(New 

Zealand) 

10 d 5dlwk 6hrId 

Resp 

Hemato 

Hepatic 

Renal 

31 

31 

31 

31 (decreased erythrocyte count) 

Hall et al. 1950 

Be0 

w 

I 

rn

5

I 

rn 

n 

n 

rn

2 

v) 

Bd Wt 31 

26 

27 

lmmunol Lymphoret 

(Beagle) 

INTERMEDIATE EXPOSURE 

Death 

(Macacus) 

Dog Id 

Monkey 30d6hrld 

10 (lymph node hyperplasia. 

lymphocyte stimulation) 

0.198 (1/4 died) 

Haley et al. 1989 

Be0 

Schepers 1964 

BeHP04 

28 Monkey 

(NS) 

51-100 d Sdlwk Ghr/d 2 (111 died) Stokinger et al. 1950 

BeS04 
Table 3-1 Levels of Significant Exposure to Beryllium - Inhalation (continued) ~~~~~~ ~~~ ~ ~ ~~ ~ 

Exposure/ LOAEL 

Duration/ 

a NOAEL Less Serious Serious Reference Key to Species Frequency 

Chemical Form figure (Strain) (Specific Route) System (mglm3) (mglm3) (mg/m3) 

INTERMEDIATE EXPOSURE 

29 Monkey 6 mo 5dlwk 6hrld Wagner et al. 1969 

0.21 (increased mortality) (Squirrel) Be0 

30 Rat 15 d 5dlwk Ghrld Hall et al. 1950 

30 (6113 males, 911 0 females died) (Wistar) Be0 

31 Rat 51-100 d 5dlwk Ghrld Stokinger et al. 1950 

0.43 (23147 died) 

(NS) BeS04 w 

32 Rat 6 mo 5dlwk Ghrld Wagner et al. 1969 rn 

0.21 (increased mortality) F 

Charles River Be0 -I

I 

m 

n 

33 Mouse 51 d 5dlwk 6hrId Stokinger et al. 1950 m 

n 

2 (4138 died) 

(NS) BeS04 s 

0) 

34 Gn Pig 51-100 d Sdlwk 6hrld Stokinger et at. 1950 

0.43 (Z34 died) 

(NS) BeS04 

35 Hamster 51-100 d 5dlwk Ghrld Stokinger et at. 1950 

2 (5110died) 

(NS) BeS04 

36 Hamster 6 mo 5dIwk 6hrId Wagner et at. 1969 

0.21 (increased mortality) (Golden Be0 

Syrian) 

37 Hamster 6 mo 5dlwk Ghrld Wagner et al. 1969 

0.62 (increased mortality) (Golden Be0 

Syrian) 
m Table 3-1 Levels of Significant Exposure to Beryllium - Inhalation (continued) m 

7J 

Exposure1 LOAEL

Duration/

a Serious Reference Key to Species Frequency NOEL Less Serious 

figure (Strain) (Specific Route) System (mglm3) (mglm3) (mglm3) Chemical Form 

INTERMEDIATE EXPOSURE 

38 Dog 51-100 d 5dlwk 6hrId Stokinger et at. 1950 

2 (415 died) 

(NS) BeS04 

39 Cat 51-100 d 5d/wk 6hr/d Stokinger et al. 1950 

0.43 (1/5 died) 

(NS) BeS04 

Systemic 

40 Monkey 15 d 5dlwk 6hr/d Hall et al. 1950 

Resp 30 

(Rhesus) Be0 0 

Bd Wt 30 (marked weight loss) m 

I 

$

-I 

41 Monkey 30d6hrld Schepers 1964 I 

Resp 0.198 (emphysema) m 

(Macacus) BeHP04 -n 

-n 

m 

Hepatic 0.198 2 

(n 

Renal 0.198 

Bd Wt 0.198 (15-39% weight loss) 

42 Monkey 51-100 d 5dlwk Ghrld Stokinger et al. 1950 

Resp 0.04 (emphysema) 

(NS) BeS04 

Bd Wt 0.43 (31% weight loss) 

w 

0 
(continued) Table 3-1 Levels of Significant Exposure to Beryllium - Inhalation 

Key to 

a 

figure 

Species 

(Strain) 

Exposure1 

Duration/ 

Frequency 

(Specific Route) System 

NOEL 

(mglm3) 

Less Serious 

(mglm3) 

LOAEL 

Serious 

(mglm3) 

Reference 

Chemical Form 

INTERMEDIATE EXPOSURE 

43 Monkey 

(Squirrel) 

6 mo 5dIwk 6hrld Resp 0.21 (inflammationof lungs) 

Wagner et al. 1969 

Be0 

Hemato 0.21 

Hepatic 0.21 

Renal 0.21 

4 Monkey 

(Squirrel) 

6 mo 5dlwk Ghrld 

Other 

Resp 

Hemato 

Hepatic 

0.21 

0.62 

0.62 

0.62 (inflammationof lungs) 

Wagner et al. 1969 

Be0 

I 

rn

5

I 

rn 

n 

n 

rn

2 

(I) 

Renal 0.62 

Bd Wt 0.62 

45 Rat 

(Wistar) 

15 d 5dlwk 6hrld Resp 

Bd Wt 

30 

30 

Hall et al. 1950 

(respiratory distress, increased 

(steady weight loss) 

rates) Be0 

46 

47 

Rat 

(Wistar) 

(Sherman) 

Rat 

(Wistar) 

180 d 5-6dlwk 4-8hrld 

10 wk 6hrld 

Resp 

Dermal 0.5 (inflammatory reaction on skin) 

0.035 (metaplasia, granulomas) 

Schepers et al. 1957 

BeS04 

Stiefel et al. 1980 

Be(N03)2 
C 

W Table 3-1 Levels of Significant Exposure to Beryllium - Inhalation (continued) rn ~ ~~ ~ 

Exposure/ 

Duration/ a Key to Species Frequency 

figure (Strain) (Specific Route) 

INTERMEDIATE EXPOSURE 

48 Rat 51-100 d 5dlwk 6hrId 

(NS) 

49 Rat 6 mo 5dlwk 6hrld 

Charles River 

50 Rat 6 mo 5dlwk 6hrId 

Charles River 

51 Gn Pig 10wk 6hrId 

(NS) 

System 

Hemato 

Hepatic 

Renal 

Bd Wt 

Resp 

Hemato 

Hepatic 

Renal 

Bd Wt 

Resp 

Hemato 

Hepatic 

Renal 

Bd Wt 

Dermal 

NOAEL 

(mglm3) 

0.04 

0.43 

2 

0.21 

0.21 

0.21 

0.21 

0.62 

0.62 

0.62 

0.62 

0.62 

LOAEL 

Less Serious 

(mglm3) 

0.43 (macrocytic anemia; 

leukocytosis) 

2 (increased serum albumin and 

globulin) 

2 (proteinurea) 

0.5 (inflammatory reaction on skin) 

Serious 

(mglm3) 

0.21 (granuloma in lung) 

Reference 

Chemical Form 

Stokinger et al. 1950 

BeS04 

Wagner et al. 1969 

Be0 

Wagner et al. 1969 

Be0 

Stiefel et al. 1980 

Be(N03)2 

I 

F 

I; 

s 

;o

s 

r 

z 

W 

h) 
Table 3-1 Levels of Significant Exposure to Beryllium - Inhalation (continued) 

a Key to 

figure Species(Strain) 

Exposure1 

Duration1 

Frequency (Specific Route) System 

NOAEL 

(mglm3) 

Less Serious 

(mglm3) 

LOAEL 

Serious 

(mglm3) 

Reference 

Chemical Form 

INTERMEDIATE EXPOSURE 

52 Hamster 

(Golden 

iirian) 

6 mo 5d/wk 6hr/d 

Resp 0.62 Wagner et al. 1969 

Be0 

Hernato 0.62 

Hepatic 0.62 

Renal 0.62 

53 Hamster 

(Golden 

Syrian) 

6 mo 5d/wk 6hrld 

Bd Wt 

Resp 

Hernato 

Hepatic 

0.62 

0.21 

0.21 

0.21 (granulomasof the lung) Wagner et al. 1969 

Be0 

w 

I 

rn

5

I 

rn 

n 

n 

rn 

0

4 

v, 

Renal 0.21 

Bd Wt 0.21 

54 Dog 

(Mongrel) 

17.5 d 5dlwk 6hr/d 

Resp 31 (emphysema, atelectasis, 

inflammation) 

Hall et al. 1950 

Be0 

Hemato 31 

Hepatic 31 

Other 31 

W 

w 
Exposure1 

Duration1 

Key to Species Frequency a 

figure (Strain) (Specific Route) 

INTERMEDIATE EXPOSURE 

Table 3-1 Levels of Sianificant ExDosure to Beryllium 

LOAEL 

NOEL Less Serious 

System (mglm3) (mglm3) 

- Inhalation 

Serious 

(mglm3) 

(continued) 

Reference 

Chemical Form 

W 

7J< 

m 

55 Dog 

(Mongrel) 

15 d 5dlwk 6hrId Cardio 30 (decrease in arterial oxygen 

tension) 

Hall et al. 1950 

Be0 

Hemato 30 (leukocytosis) 

Bd Wt 30 (7-14% body weight loss) 

56 Dog 

(Mongrel) 

40 d 5dlwk 6hrId 

Resp 

Cardio 

Hemato 

Hepatic 

Renal 3.6 

3.6 

3.6 

3.6 

(decrease in arterial oxygen 

(macrocytic anemia) 

(decreased serum protein) 

tension) 

3.6 (emphysema) 

Hall et at. 1950 

Be0 

I 

F

5

I 

m 

-n 

n 

rn 

0) 

9 

w 

Bd Wt 3.6 (anorexia and 25% weight loss) 
(continued) Table 3-1 Levels of Significant Exposure to Beryllium - Inhalation 

~~ 

LOAEL Exposure1 

Duration1 Reference a NOAEL Less Serious Serious Key to Species Frequency Chemical Form figure (Strain) (Specific Route) System (mglm3) (mglm3) (mglm3) 

INTERMEDIATE EXPOSURE 

Stokinger et al. 1950 57 Dog 51-100 d 5dlwk Ghrld 0.04 (emphysema) Resp BeS04 (NS) 

Cardio 0.04 (decreased arterial oxygen 

tension) 

Hemato 0.43 (leukocytosis) 

0.04 (macrocytic anemia) 

Hepatic 0.04 (increased serum albumin and 

globulin) I 

m 

Renal 0.04 0.43 (proteinurea) 5

I 

Bd Wt 0.04 (body weight loss) rn 

n 

n 

rn 

58 Rabbit 60 d 5dlwk Ghrld Hall et al. 1950 2

Resp 30 CJ-J

Be0 (New 

Zealand) 

Hemato 30 (macrocytic anemia) 

Bd Wt 30 

Stokinger et al. 1950 

59 Rabbit 51-100 d 5dlwk Ghrld 0.04 (actelectasis) Resp BeS04 (NS) 

Hemato 0.04 0.43 (macrocytic anemia; 

leu kocytosis) 

Bd Wt 2 

w 

cn 
Table 3-1 Levels of Significant Exposure to Beryllium - Inhalation (continued) m 

rn 

Key to 

a 

Species 

Exposure/ 

Duration1 

Frequency NOAEL Less Serious 

LOAEL 

Serious Reference 

;(1 

Iz

C

3 

2 

figure (Strain) (Specific Route) System (mglm3) (mglm3) (mglm3) Chemical Form 

INTERM EDlATE EXPOSURE 

60 Cat 

(Mongrel) 

15 d 5dIwk 6hrld 

Resp 30 

Hall et al. 1950 

Be0 

Bd Wt 30 (anorexia, severe weight loss, 

emaciation) 

61 Cat 

(NS) 

51-100 d 5dlwk 6hrId 

Resp 0.04 (emphysema) Stokinger et at. 1950 

BeS04 

Bd Wt 0.04 (severe weight loss) w 

I 

62 

63 

Pig 51 5dIwk 6hrId 

(NS) 

lmmunol Lymphoret 

Rat 10 wk 6hrld 

(Wistar) 

Bd Wt 

0.5 (increased T-cell activity) 

2 (28% weight loss) Stokinger et al. 1950 

BeS04 

Stiefel et al. 1980 

Be(N03)2 

m

5

I 

rn 

n 

-n 

rn 

64 Gn Pig 

(NS) 

10 wk 6hrld 

0.5 (increased T-cell activity) 

Stiefel et al. 1980 

Be(N03)2 

Cancer 

65 

(Wistar) 

(Sherman) 

Rat 180 d 5-6dlwk 4-8hrld 0.035 (CEL: lung cancer) Schepers et al. 1957 

BeS04 

CHRONIC EXPOSURE 

Death 

66 Rat 

(SpragueDawley) 

72 wk 5dlwk 7hrld 0.034 Reeves et al. 1967 

BeS04 

(increased mortality of females) 

Systemic 

67 Human 12.6 yr average Resp 0.001 2 (breathing difficulties, scarring 

of the lung) 

Cullen et al. 1987 

mix 
Exposure/ 

Duration/

a 

Key to Species Frequency 

figure (Strain) (Specific Route) 

CHRONIC EXPOSURE 

Table 3-1 Levels of Significant Exposure to Beryllium - Inhalation 

LOAEL 

NOEL Less Serious Serious 

System (mglm3) (mglm3) (mglm3) 

(continued) 

Reference 

Chemical Form 

m 

7J

m 

5I 

r

C

I 

68 Human (OCCUP) Resp 0.00052 (chronic beryllium disease) 

Cullen et al. 1987 

mix 

69 Human occup Resp 0.00055 (beryllium sensitization and 

chronic beryllium disease) 

Kreiss et al. 1996 

Be0 

70 Monkey 

(Squirrel) 

12-23 mo 5dtwk 6hr/d Resp 

Hemato 

Hepatic 

Renal 

Bd Wt 

0.62 

0.62 

0.62 

0.62 

0.62 (inflammationof lungs) Wagner et al. 1969 

Be0 

I 

rn

5

I 

rn 

n 

n 

rn

2 v) 

w 

71 Monkey 

(Squirrel) 

12-23 mo 5dlwk 6hrId Resp 0.21 (inflammationof lungs) 

Wagner et al. 1969 

Be0 

Hemato 0.21 

Hepatic 0.21 

Renal 0.21 

Bd Wt 0.21 

72 Rat 

(SpragueDawley) 

72 wk 5dlwk 7hrld 

Resp 

Bd Wt 

0.034 

0.034 

(inflammation and proliferation 

in lung) 

(decrease in body weight) 

Reeves et al. 1967 

BeS04 
Exposure1 

Table 3-1 Levels of Significant Exposure to Beryllium - Inhalation 

LOAEL 

(continued) m 

A

< 

rn 

a Key to 

figure 

Species 

(Strain) 

Duration1 

Frequency 

(Specific Route) System 

NOAEL 

(mglm3) 

Less Serious 

(mglm3) 

Serious 

(mglm3) 

Reference 

Chemical Form 

c

I 

CHRONIC EXPOSURE 

73 Rat 

(Sherman) 

6-18 mo 5dIwk 6hrId Resp 0.0547 (inflammation and fibrosis of the 

lung) 

Votwald and Reeves 1959 

BeS04 

74 Rat 

(Sherman) 

6-18 mo 5dlwk 6hrld Resp 0.006 (inflammation and fibrosis of the 

lung) 

Vorwald and Reeves 1959 

Be0 

75 Rat 12-17 mo 5dlwk 6hrId 

Charles River Resp 0.21 (granuloma in lung) Wagner et al. 1969 

Be0 

Hemato 

Hepatic 

Renal 

Bd Wt 

0.21 

0.21 

0.21 

0.21 

m

5

I 

rn 

n 

n 

Fl

2 

76 Rat 12-1 7 mo 5dIwk 6hrld 

Charles River Resp 0.62 (consolidation of lung) 

Wagner et al. 1969 

Be0 

Hemato 0.62 

Hepatic 0.62 

Renal 0.62 

Bd Wt 0.62 (decreased body weight gain) 
m Table 3-1 Levels of Significant Exposure to Beryllium - Inhalation (continued) rn 

7J 

a Key to 

figure 

Species 

(Strain) 

Exposure/ 

Duration/ 

Frequency 

(Specific Route) System 

NOAEL 

(mglm3) 

Less Serious 

(mglm3) 

LOAEL 

Serious 

(mg/m3) 

Reference 

Chemical Form 

r

C 

z 

$ 

CHRONIC EXPOSURE 

77 Hamster 

(Golden 

Syrian) 

12-17 rno 5dlwk 6hrId Resp 0.21 (granulomas in the lung) Wagner et al. 1969 

Be0 

Hernato 0.21 

Hepatic 0.21 

Renal 0.21 

78 Hamster 

(Golden 

Syrian) 

12-17 rno 5d/wk 6hrId 

Bd Wt 

Resp 

Hernato 

0.21 

0.62 

0.62 

Wagner et al. 1969 

Be0 

w 

I 

rn 

-4

I 

? 

rn 

n 

rn 

n 

Hepatic 0.62 

Renal 0.62 

Bd Wt 0.62 

79 

lmmuno/ Lymphoret 

Human occup 0.00052 (increased T-cell activity) 

Cullen et al. 1987 

mix 

80 

Cancer 

(Rhesus) 

Monkey 63 wk 5dlwk 6hrJd 0.035 (CEL: lung cancer) 

Vorwald 1968 

BeS04 

81 Rat 

(SpragueDawley) 

72 wk 5dlwk 7hrld 0.034 (CEL: lung cancer) 

Reeves et al. 1967 

BeS04 

W 

W 
Table 3-1 Levels of Significant Exposure to Beryllium - Inhalation (continued) m

3 

rn ~~ ~~ ~~~ ~~ ~~ ~ 

Exposure/ LOAEL i

1 Duration/ c 

a NOAEL Less Serious Serious Reference I Key to Species Frequency 

figure (Strain) (Specific Route) System (mglm3) (mg/m3) (mdm3) Chemical Form 

CHRONIC EXPOSURE 

82 Rat 6-18 mo 5dIwk 6hrId Vorwald and Reeves 1959 

0.0547 (CEL: lung cancer) (Sherman) BeS04 

83 Rat 6-18 mo 5dlwk Ghrld Vorwald and Reeves 1959 

0.006 (CEL: lung cancer) (Sherman) Be0 

84 Rat 12-17 mo 5dIwk 6hrId Wagner et al. 1969 

0.62 (CEL: lung cancer) Charles River Be0 

u 

I 

m ~~ 

a The number corresponds to entries in Figure 3-1. ?

-I

I 

Bd Wt = body weight; Be = Beryllium; BeC12 = beryllium chloride; BeF2 = beryllium fluoride; BeHP04 = beryllium hydrogen phosphate; Be(N03)2 = beryllium nitrate; rn 

n Be0 = beryllium oxide; BeP04 = beryllium phosphate; BeS04 = beryllium sulfate; Cardio = cardiovascular; CEL = cancer effect level; d = day@); Endocr = endocrine; n 

Gn pig = guinea pig; hemato = hematological: hr = hour(s); LC50 = lethal concentration, 50% kill; LOAEL = lowest-observed-adverse-effectlevel; min = minute(s); mix = beryllium 0 

m 

oxides and ores in a refinery; mo = month(s); Musclskel = musculoskeletal; NOAEL = no-observed-adverse-effect level; occup = occupational; Resp = respiratory; wk = week@) -I 

0) 

P 

0 
Figure 3-1. Levels of Significant Exposure to Beryllium - Inhalation 

Acute (114 days) W 

rn 

;D 

Systemic r 

C 

$ 

z 

rnglrn3 

1000 

1oc 024d 

I*' 

I 

0229 014r 025h 014r @25h 014r 0229 014r 025h rn

e

i

I 

02k a10k @10k 

1( 

018r 

04r 013r 

a1 5r 

@Ilk 012k 

0.1 

c-Cat -Humans f-Ferret n-Mink Cancer Effect Level-Animals V Cancer Effect Level-Humans : LD50/LC50 Minimal Risk Level 

d-Dog k-Monkey j-Pigeon o-Other 0LOAEL, More Serious-Animals A LOAEL, More Serious-Humans 

r-Rat m-Mouse e-Gerbil 0LOAEL, Less Serious-Animals A LOAEL, Less Serious-Humans : foreffects P,

p-Pig h-Rabbit +Hamster 0NOAEL- Animals A NOAEL- Humans A other than 

q-Cow a-Sheep 9-Guinea Pig Cancer 
mglm3 

1000 

100 

10 

1 

c-Cat 

d-Dog

r-Rat 

p-Pig

q-Cow 

Figure 3-1. Levels of Significant Exposure to Beryllium - Inhalation (Confinued) 

Acute (114 days) 

Systemic -0t 

@10k @24d 

0229 014r 025h 0229 025h 014r 

OlOk @10k .10k 

@26d 

Q21rn 

-Humans f-Ferret n-Mink Cancer Effect Level-Animals Cancer Effect Level-Humans 

k-Monkey j-Pigeon o-Other 0LOAEL, More Serious-Animals A LOAEL, More Serious-Humans 

m-Mouse e-Gerbil (3LOAEL, Less Serious-Animals A LOAEL, Less Serious-Humans 

h-Rabbit s-Hamster 0NOAEL -Animals NOAEL- Humans 

a-Sheep g-Guinea Pig 

w 

LD50/LC50

; Minimal Risk Level 

: for effects P 

h) other than 

Cancer 

0.1 
Figure 3-1.Levels of Significant Exposure to Beryllium - Inhalation (Continued) 

Intermediate (15-364 days) m 

rn 

Systemic 

rnglrn3 

100 

@55d 054d 

1c 

056d @56d @56d a56d 

@48r 

1 

052s @44k 050r 052s 044k 050r 052s 044k 050r 

@57d @48r @59h 

0.1 

061~O57d 042k 046r059h a57d @57d 048r 059h @57d 

0.01 

c-Cat -Humans f-Ferret n-Mink Cancer Effect Level-Animals Cancer Effect Level-Humans LD50/LC50

d-Dog k-Monkey j-Pigeon o-Other 0LOAEL, More Serious-Animals A LOAEL, More Serious-Humans : Minimal Risk Level 

r-Rat m-Mouse e-Gerbil aLOAEL, Less Serious-Animals A LOAEL, Less Serious-Humans : foreffects P

0

p-Pig h-Rabbit s-Hamster 0NOAEL -Animals A NOAEL- Humans other than 

n-Cnw a-Sheen a-Guinea Pio Cancer 
Figure 3-1. Levels of Significant Exposure to Beryllium - Inhalation (Continued) 

Intermediate (15-364 days) m 

rn 

rnglrn3 

100 

.60c .55d 040k .45r 058h 054d

10 

w 

056d .56d I

rn

F 

a48r 048r 059h .62p I

-I 

rn 

n 

n 

rn 1 7 

v) 052s 044k 050r 052s 044k 050r 

a519 a47r a649 063r 

a57d 048r .42k 

053s 04lk043k 049r 043k 

0.1 

057d .61c a57d +65r 

*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 V Cancer Effect Level-Humans LD50/LC50

d-Dog k-Monkey j-Pigeon o-Other LOAEL, More Serious-Animals A LOAEL, More Serious-Humans I Minimal Risk Level 

r-Rat m-Mouse e-Gerbil (D LOAEL, Less Serious-Animals A LOAEL, Less Serious-Humans I for effects P 

P 

p-Pig h-Rabbit s-Hamster 0NOAEL -Animals NOAEL - Humans other than q-CowsjheeP9-GuineaPi~__~___.__-___. Cancer 
Figure 3-1. Levels of Significant Exposure to Beryllium - Inhalation (Continued) 

Chronic (2365days) 

Svstemic 

mglm3 

1 

078s 870k 876r 078s 070k 076r 078s 070k 076r 078s 070k076r 078s 070k 876r *84r 

077s 871 k 075r 077s 071 k075r 077s 071 k 075r 077s 071 k075r 077s 071 k 075r 

0.1 

873r *82r 

872r 872r *80k *81r 

0.01 

*83r 

w 

I 

A67 0.001 F 

A68 A69 A79 

0.0001 

10-4 

Estimated 

Upper-Bound 1E-5 

Human Cancer 

10-5 Risk Levels 

1E-6 

10-6-

1 E-7 

*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. 10-7-

1E-8 

c-Cat -Humans f-Ferret n-Mink Cancer Effect Level-Animals Cancer Effect Level-Humans LD50lLC50 

d-Dog k-Monkey j-Pigeon o-Other 0LOAEL, More Serious-Animals A LOAEL, More Serious-Humans : Minimal Risk Level P 

cn r-Rat m-Mouse e-Gerbil 8LOAEL, Less Serious-Animals A LOAEL, Less Serious-Humans 1 for effects 

p-Pig h-Rabbit s-Hamster 0NOAEL -Animals A NOAEL- Humans A other than 

a-Cow a-SheeD a-Guinea Pia Cancer 
 

BERYLLIUM 46 

3. HEALTH EFFECTS 

values for each systemic effect in each species and duration category are recorded in Table 3-1 and 

plotted in Figure 3-1. 

Respiratory Effects. There is extensive evidence in humans that the respiratory tract is one of the 

primary targets of beryllium toxicity following inhalation exposure. In general, noncancerous respiratory 

effects can be divided into two categories: acute beryllium disease and chronic beryllium disease, also 

referred to as berylliosis or chronic berylliosis. Acute beryllium disease is a fulminating inflammatory 

reaction of the entire respiratory tract. The respiratory tract symptoms range from mild nasopharyngitis to 

a severe chemical pneumonitis, which may be fatal. Acute beryllium disease is usually associated with 

exposure to high concentrations of soluble beryllium compounds. VanOrdstrand et al. (1945) describe a 

number of cases of acute beryllium disease among workers exposed to beryllium sulfate, beryllium oxide, 

beryllium fluoride, and beryllium oxyfluoride. Signs and symptoms observed in the affected workers 

included irritation of the nasal and pharyngeal mucous membranes, sore nose and throat, weight loss, 

labored breathing, decreased vital capacity, anorexia, and increased fatigue. In a 1948 investigation of 

acute beryllium pneumonitis in three U.S. plants producing beryllium compounds from the ore and in 

laboratories and shops engaged in research in ceramics and metallurgy of beryllium, all cases of beryllium 

pneumonitis were associated with concentrations >0.1 mg beryllium/m3

, primarily as beryllium sulfate or 

beryllium fluoride (Eisenbud et al. 1948a). The syndrome of acute beryllium disease has been virtually 

eliminated in workers first exposed to beryllium after 1950 (initiation of strict exposure limits), except in 

instances where there is accidental exposure to high levels of beryllium (Eisenbud and Lisson 1983). 

Chronic beryllium disease (CBD) is an inflammatory lung disease characterized by the formation of 

granulomas with varying degrees of interstitial fibrosis. Chronic beryllium disease is a beryllium-specific 

immune response with primary manifestations in the lung. The symptoms associated with chronic 

beryllium disease include chest pain, cough, and/or dyspnea with relatively mild exertion. The clinical 

syndrome of chronic beryllium disease was first described by Hardy and Tabershaw (1946) in fluorescent 

lamp workers. Seventeen chronically exposed workers developed anorexia, dyspnea, cough, easy fatigue, 

and weakness. An autopsy on one of the workers revealed increased lung weight, diffuse fibrosis, 

granuloma, abnormal epithelial lining of the bronchioles, and abnormal alveoli and vasculature. Prior to 

the adoption of stringent industrial hygiene measures, the incidence of chronic beryllium disease among 

beryllium workers was high. Historically, a number of criteria were used for the diagnosis of chronic 

beryllium disease: evidence of beryllium exposure, evidence of lower respiratory tract disease and clinical 

course consistent with chronic beryllium disease, reticulonodular infiltrates on chest x-ray, obstructive or 

restrictive deficits in lung function or a low diffusing capacity for carbon monoxide, and pathological 
BERYLLIUM 47 

3. HEALTH EFFECTS 

evidence of non-caseating granulomas and/or mononuclear cell interstitial infiltrates (Newman et al. 

1989). Technological developments in the 1980s (e.g., fiber optic bronchoscopy and transbronchial 

biopsy methods, development of the beryllium lymphocyte proliferation test) now allow for the detection 

of subclinical cases of chronic beryllium disease and beryllium sensitization in the absence of chronic 

beryllium disease. Newman et al. (1989) proposed that chronic beryllium disease can be classified into 

three stages: (1) beryllium sensitization—consistent abnormal results for blood and/or lung BeLPT) 

results, (2) subclinical chronic beryllium disease—sensitized individuals with histopathological evidence 

but no clinical signs, and (3) clinical chronic beryllium disease—sensitized individuals with 

histopathological evidence with respiratory symptoms, changes on chest radiographs, or altered 

pulmonary physiology. 

Although instituting regulatory exposure limits and improved hygiene practices has decreased the number 

of cases of chronic beryllium disease among beryllium workers, new cases of chronic beryllium disease 

are still being identified in beryllium workers. Cotes et al. (1983) examined 130 workers employed at a 

beryllium manufacturing facility for at least 6 months during the period of 1952–1963. Based on clinical 

evaluation including chest x-rays and lung function tests, there were four definite cases of chronic 

beryllium disease and one probable case of chronic beryllium disease. Another two workers had chest 

x-rays consistent with chronic beryllium disease, but did not have any other alterations. Beryllium 

exposure levels were estimated using facility records for total airborne concentrations over the period of 

1952–1960. The mean exposure levels for different job processes were 0.029–0.72 μg beryllium/m3

 in 

1952 and 0.022–0.21 μg beryllium/m3

 in 1960. Two of the confirmed cases of chronic beryllium disease 

worked in an area of the facility where beryllium concentrations were 0.04 and 0.18 μg beryllium/m3

 in 

1952 and 1960, respectively. Because these exposure levels were based on general air samples, they may 

not be representative of breathing zone beryllium levels. 

Five cases of chronic beryllium disease were reported among workers exposed to beryllium oxide fumes 

at a precious metals refinery (Cullen et al. 1987). The five workers had abnormal chest x-rays, 

noncaseating granulomas, pulmonary fibrosis, and abnormal results for the bronchoalveolar lavage 

beryllium lymphocyte proliferation test (BeLPT). A health survey of 45 workers at the same facility was 

also conducted (Cullen et al. 1987). Eighteen workers reported lower respiratory tract symptoms (cough, 

dyspnea, wheezing). Among these 18 workers, 7 also had abnormal x-rays, such as focal scarring. Time 

weighted-average personal air samples, measured during a 2-week period in 1983, throughout the refinery 

ranged from 0.22 to 43 μg beryllium/m3

, with a mean of 1.2 μg beryllium/m3. Four of the five workers 

with chronic beryllium disease worked in the furnace area, where the mean concentration was 0.52 μg 
BERYLLIUM 48 

3. HEALTH EFFECTS 

beryllium/m3. This concentration is considered a LOAEL for chronic beryllium disease. However, it is 

possible that the air samples collected during a 2-week period may not be reflective of current or past 

exposure conditions. 

Reversible respiratory effects were observed in a group of beryllium extraction workers examined by 

Sprince et al. (1978). Health surveys (including measurement of lung function and x-rays) were 

conducted in 1971 and 1974. When lung function test results and arterial blood gas results were 

compared to the 1971 values, a slight statistically significant decrease in peak expiratory flow rate, 

increase in alveolar-arterial O2 tension and decrease in alveolar-arterial CO2 tension were observed in a 

group of 111 workers. When workers with radiological abnormalities suggestive of interstitial disease 

were re-examined in 1974, nine workers had normal radiographs and nine had radiographs suggestive of 

interstitial disease; it should be noted that some of these workers had previous exposure to asbestos, silica, 

or soft coal. Improvement in hypoxia and decreased alveolar-arterial O2 tension were observed among 

13 workers diagnosed with hypoxia in 1971; no change in lung function was observed in this group. The 

improvement in respiratory effects corresponded to a dramatic decrease in peak air concentrations of 

beryllium. 

Several investigators have conducted screening studies to assess the occurrence of beryllium sensitization 

and subclinical chronic beryllium disease among beryllium workers. Kreiss et al. (1993a) and Stange et 

al. (1996b, 2001) examined workers at the Rocky Flats Technology site involved in the production of 

nuclear weapons, Kreiss et al. (1997) and Newman et al. (2001) examined workers at other beryllium 

production facilities, and Deubner et al. (2001b) examined beryllium mine workers and workers at a 

beryllium extraction facility. In the Kreiss et al. (1993a) study, 895 current workers were examined and 

beryllium sensitization, defined as consistently abnormal BeLPT results, was detected in 17 workers 

(1.9%). All of these workers had normal chest x-rays. Sixteen of the subjects with beryllium 

sensitization underwent clinical evaluation (bronchoalveolar lavage BeLPT and transbronchial lung 

biopsy). Chronic beryllium disease (defined as having granulomas on lung biopsy and abnormal blood or 

bronchoalveolar lavage [BAL] BeLPT results) was diagnosed in 13 of the subjects. Forty-two subjects 

had abnormal chest x-rays, 40 of which underwent clinical evaluation. An additional case of chronic 

beryllium disease was detected in this group (this subject had inconsistently abnormal BeLPT results). 

Thus, the incidence of chronic beryllium disease in this population was 15/895 (1.7%; one worker 

refusing clinical evaluation was included in the beryllium disease group because he had ventilatory 

abnormalities suggestive of restrictive disease). The beryllium sensitized individuals did not significantly 

differ from the whole cohort in terms of gender, age, history of atopic disease, cigarette smoking status or 
BERYLLIUM 49 

3. HEALTH EFFECTS 

pack years, prevalence of respiratory symptoms, spirometric abnormalities, or profusion of small 

opacities on chest x-rays. 

Stange et al. (1996b) examined 4,397 current and former employees at the same facility; it is not known if 

any of the workers were also included in the Kreiss et al. (1993a) study. Beryllium sensitization was 

found in 78 of the workers (1.8%); the beryllium sensitization rate was similar in the current and former 

employees (1.2 versus 1.9%). Of the beryllium sensitized workers, 29 were diagnosed as having chronic 

beryllium disease (29/4397, 0.66%); chronic beryllium disease was defined as having histologic evidence 

of pulmonary granulomatous disease and a positive BAL BeLPT result. Environmental beryllium levels 

were measured in the main beryllium production building using fixed airhead samplers (measured for the 

period of 1970–1988) and personal air monitoring devices (1984–1987); the mean concentrations were 

0.016 and 1.04 μg beryllium/m3

, respectively; the 1.04 μg beryllium/m3 is considered a LOAEL because 

it more accurately reflected beryllium concentrations in the breathing zone. However, this value does not 

take into consideration beryllium levels prior to 1984 and may not be representative of historical 

beryllium levels. 

A more recent study by this group examined 5,173 workers at the Rocky Flats facility (Stange et al. 

2001). Confirmed abnormal blood BeLPT results were found in 98 workers (3.33%). Three years after 

the initial screening, 2,891 workers were re-examined; an additional 56 workers had abnormal blood 

BeLPT results. The total beryllium sensitization rate was 4.54% (154/5173). The workers with abnormal 

BeLPT results or with a small opacity profusion of 1/0 or greater in their chest x-ray underwent medical 

evaluations for chronic beryllium disease. The criteria for diagnosis of chronic beryllium disease were 

history of beryllium exposure, histopathologic evidence on biopsy of noncaseating granulomas or 

mononuclear cell infiltrates in the lung, and a positive blood or BAL BeLPT. Seventy-four cases of 

chronic beryllium disease were diagnosed during the initial screening period and 7 additional cases were 

diagnosed at the 3-year screening. Beryllium sensitization and chronic beryllium disease were found in 

male and female workers employed at the facility for <5 years. Increased odds ratios for beryllium 

sensitization were found for workers in the health physics (odds ratio=2.867; 95% confidence interval 

[CI]=1.12–7.36), beryllium machinist (odds ratio=3.044; 95% CI=1.95–4.77), construction trades (odds 

ratio=2.426; 95% CI=1.48–3.97), and general machinist (odds ratio=1.345; 95% CI=1.00–1.82) job group 

categories. 

Viet et al. (2000) designed a case control study of workers at the Rocky Flats facility to evaluate the risks 

associated with various levels of historical beryllium exposure. Seventy four workers diagnosed as 
BERYLLIUM 50 

3. HEALTH EFFECTS 

beryllium sensitive and 50 workers with chronic beryllium disease were matched by age, smoking status, 

gender, and race to an equal number of controls. Workers were diagnosed as beryllium sensitive if two 

blood BeLPT results were positive and the clinical evaluation did not reveal chronic beryllium disease; 

the criteria used to diagnosis chronic beryllium disease were exposure to beryllium, positive blood and 

lung BeLPT results and noncaseating granulomas on lung biopsy. Historical beryllium exposure levels 

were estimated using fixed airhead samples in one building (beryllium machine shop); annual exposure 

levels were estimated by averaging air samples from 2 random days each month. An individual’s 

exposure level was estimated using annual exposure levels; the individual’s work history by job location, 

task, and time period; and assignment of relative exposure estimates to each combination of job location, 

task, and time period as compared with the beryllium shop machinists. For the chronic beryllium disease 

cases, the mean exposure level (0.070 versus 0.025 μg/m3

), cumulative exposure level (1.35 versus 

0.38 μg-years/m3

), and duration of employment (19.1 versus 14.4 years) were significantly higher than 

for the controls. For the beryllium sensitive cases, the mean exposure level (0.036 versus 0.026 μg/m3

) 

was significantly higher than for controls, but there was no significant differences for cumulative 

exposure level (0.54 versus 0.40 μg-years/m3

) or duration of employment (13.2 versus 14.5 years). 

Employment start date was not significantly different for the cases versus control comparisons. 

Comparisons between the chronic beryllium disease cases and beryllium sensitive cases revealed 

significant differences in mean exposure level (0.070 versus 0.036 μg/m3

), cumulative exposure level 

(1.35 versus 0.54 μg-years/m3

), duration of employment (19.1 versus 13.2 years), and employment start 

date (1964.9 versus 1970.2). Significant relationships between chronic beryllium disease and both 

cumulative and mean beryllium exposure were also found using logistic regression analysis; significant 

relationships were not found for beryllium sensitization. This study cannot be used to establish a LOAEL 

for chronic beryllium disease or beryllium sensitization because method used to assess beryllium 

exposure (fixed airhead samples) may not be representative of beryllium levels in personal breathing 

zones. The study authors note that fixed airhead sampling may underestimate breathing zone levels by a 

factor of 0.5–9. 

Beryllium sensitization and subclinical chronic beryllium disease has also been found in workers exposed 

to beryllium oxide at beryllia ceramics plants. Eight cases of beryllium sensitization were found among 

136 current employees at the plant (Kreiss et al. 1996). Five of these workers had consistently abnormal 

BeLPT results and were diagnosed with chronic beryllium disease based on the observation of 

granulomas. Two workers had inconsistently abnormal BeLPT results and no granulomas; however, 

2 years after the initial examination, one of these workers had symptoms of chronic beryllium disease (the 

other refused clinical follow-up). A seventh case of chronic beryllium disease was detected in a worker 
BERYLLIUM 51 

3. HEALTH EFFECTS 

who initially had normal BeLPT results but later developed a nonhealing granulomatous response to a 

beryllium-contaminated skin wound and an abnormal BeLPT result. Seven of the eight beryllium 

sensitized workers were machinists; the beryllium sensitization rate among the machinists was 

14.3 versus 1.2% for all other workers. The beryllium exposure levels for the beryllium-sensitized 

workers ranged from 0.2 to 1.1 μg beryllium/m3

; the median concentration was 0.55 μg/m3, this is a 

LOAEL for beryllium sensitization and chronic beryllium disease. 

Additional cases of beryllium sensitization and chronic beryllium disease were identified in a follow-up 

to this study (Henneberger et al. 2001). This study examined 151 workers employed at a beryllium 

ceramics manufacturing facility; 77 of the workers were employed before 1992 (long-term workers, 76 of 

them participated in the first beryllium screening study [Kreiss et al. 1996]) and the remaining workers 

began employment at the facility after 1992 (short-term workers). Breathing zone and general area 

sample measurements taken from 1981 (when full production of beryllium ceramics began) to 1998 were 

used to estimate mean, cumulative, and peak exposure levels. The median and mean exposure levels were 

0.39 and 14.9 μg/m3

, respectively, for long-term workers and 0.28 and 6.1 μg/m3, respectively, for shortterm workers. Using blood BeLPT, 15 cases of beryllium sensitization were diagnosed; 8 cases among 

long-term workers and 7 among short-term workers. Six of these workers were diagnosed as having 

chronic beryllium disease (defined as borderline or abnormal BAL BeLPT and/or characteristic 

granulomas on lung biopsy). Seven of the eight workers with chronic beryllium disease were long-term 

workers. Among long-term workers, no relationships between the prevalence of beryllium sensitization 

and time since first exposure, mean exposure level, or cumulative exposure level were found. However, a 

higher prevalence of beryllium sensitized workers was seen in the workers with the highest peak exposure 

levels. For the short-term workers, positive associations between prevalence of beryllium sensitization 

and mean, cumulative, and peak exposure levels were found. 

A study of 627 workers at a beryllium manufacturing facility found 43 cases of beryllium sensitization 

(6.9%) (Kreiss et al. 1997). Chronic beryllium disease was diagnosed in 24 of the beryllium sensitized 

workers (incidence of 4.6%). The highest incidence of chronic beryllium disease was found in ceramic 

workers exposed to beryllium oxide (9.0%). The only available monitoring data for this facility is 

historic environmental beryllium measurements taken between 1984–1993. However, these monitoring 

data can not be used to establish a LOAEL for chronic beryllium disease because ceramic product 

manufacturing (the workers with the highest disease incidence) was terminated before 1984. 
BERYLLIUM 52 

3. HEALTH EFFECTS 

Newman et al. (2001) conducted a medical surveillance in a beryllium metal machining facility following 

the detection of an index case of chronic beryllium disease in 1995. All current employees were tested 

with the blood BeLPT between 1995 and 1997 and were retested 2 years after the initial screening. The 

mean age of the current workers was 39 years and the mean duration of exposure was 11.7 years. Of the 

235 workers initially tested, 15 had confirmed abnormal blood BeLPT results. Eleven of these workers 

underwent clinical evaluation; 8 were found to have chronic beryllium disease with granulomas and/or 

mononuclear cell infiltrates on transbronchial lung biopsy. One worker had an abnormal BAL 

(bronchioalveolar lavage) BeLPT and lymphocytes in the BAL fluid, but no evidence of granulomas or 

infiltrates; this worker was classified as having probable chronic beryllium disease. The remaining three 

workers were classified as beryllium sensitized without evidence of chronic beryllium disease. During 

the first 2-year interval testing phase (187 workers were retested), five additional workers had 

consistently abnormal BeLPT results; three of these workers were diagnosed as having chronic beryllium 

disease and one was classified as probably having chronic beryllium disease. During the second interval 

testing phase, 109 workers were tested and two cases of abnormal BeLPT results were found. Both of 

these individuals were diagnosed as having chronic beryllium disease. Thus, the total number of 

beryllium-sensitized workers was 22. Of the 19 undergoing clinical evaluation, 13 workers were 

diagnosed with chronic beryllium disease characterized as granulomas and/or mononuclear cell infiltrates 

on lung biopsy, and 2 workers were diagnosed with probable chronic beryllium disease. No difference in 

duration of employment was found between the workers with chronic beryllium disease and the beryllium 

sensitized workers. The workers with chronic beryllium disease were older than the beryllium sensitized 

workers (41 years versus 33.5 years); three of the workers were employed for <3 months. With the 

exception of the index case, most of the workers with chronic beryllium disease were at the very early 

stages and had minimal abnormalities on pulmonary function or on exercise capacity testing. 

Kelleher et al. (2001) expanded the results of the Newman et al. (2001) by examining the relationship 

between beryllium exposure and beryllium sensitization and chronic beryllium disease. Beryllium 

exposure levels for 20 of the beryllium workers with beryllium sensitization (7 workers) or chronic 

beryllium disease (13 workers; includes 2 workers with probable chronic beryllium disease) were 

compared with beryllium exposure levels for 206 workers employed at the same facility who were 

negative for beryllium sensitization. No significant differences in age, employment duration, or smoking 

status were found between the cases and controls. A significantly higher proportion of the cases worked 

as machinists (odds ratio=4.4; 95% CI=1.1–17.6). The median total beryllium exposure level based on 

personal samplers was 0.13 μg/m3

. The cases tended to have higher cumulative and median beryllium 

exposure levels and cumulative exposures to particle sizes of <6 or <1 μm, but the differences were not 
BERYLLIUM 53 

3. HEALTH EFFECTS 

statistically significant. The respective mean and median cumulative exposures were 6.09 and 

2.93 μg/m3

-years for the cases and 2.27 and 1.24 μg/m3-years for the controls. None of the cases had 

lifetime-weighted average beryllium exposure levels of <0.02 μg/m3

; 60% of the cases had lifetimeweighted averages of >0.20 μg/m3

. In the control group, 11% of the workers were exposed to 

<0.02 μg/m3

 and 48% were exposed to >0.20 μg/m3. 

Deubner et al. (2001b) examined 75 workers at a beryllium ore mining and milling facility in Utah. The 

workers involved in the mining operation were primarily exposed to beryl ore or bertrandite ore and the 

milling operation workers were exposed to these ores and beryllium hydroxide. Three of the workers had 

abnormal blood BeLPT results and one had an unconfirmed positive test. The four workers were longterm employees involved in the facility’s milling operations. Two of the workers with confirmed BeLPT 

results underwent biopsy and BAL BeLPT; one of these workers was diagnosed with chronic beryllium 

disease (granulomatous lung disease on biopsy). The worker with chronic beryllium disease also worked 

at another beryllium facility for 10 years where he was involved in beryllium metal and beryllium oxide 

production. General area, breathing zone, and personal lapel samples were used to estimate historical 

beryllium exposure. The mean general area, breathing zone, and personal lapel samples ranges were 

0.3–1.1, 1.1–8.1, and 0.05–6.9 μg/m3

, respectively. Because no cases of beryllium sensitization or 

chronic beryllium disease were found in workers who only worked in the mines, the study author 

suggested that the form of beryllium may influence the risk for developing beryllium sensitization or 

chronic beryllium disease. 

Although chronic beryllium disease is usually associated with occupational exposure to beryllium at 

manufacturing facilities, it has also been reported in dental technicians (Brancaleone et al. 1998; Kotloff 

et al. 1993), in individuals living near beryllium manufacturing facilities, and in families of beryllium 

workers who wore contaminated clothing at home (Chesner 1950; Dattoli et al. 1964; Eisenbud et al. 

1949; Lieben and Metzner, 1959; Lieben and Williams 1969). Eisenbud et al. (1949) examined 

10,000 residents living within 1 mile of a beryllium manufacturing facility. Eleven cases of chronic 

beryllium disease (based on radiological evidence) were initially detected; one case was eliminated due to 

exposure to beryllium dust on work clothes. Three more cases were detected in a follow-up study 

(Sterner and Eisenbud 1951). The study authors estimated that the beryllium concentrations 0.75 miles 

from the facility were 0.01–0.1 μg beryllium/m3

. Because the affected residents lived within 0.75 miles 

of the facility, the 0.01–0.1 μg/m3

 concentration range is a NOAEL for clinical chronic beryllium disease. 
BERYLLIUM 54 

3. HEALTH EFFECTS 

Clinical chronic beryllium disease is associated with impaired lung function. Lung function testing in 

individuals with chronic beryllium disease has shown reduced vital capacity and total lung capacity, 

increased alveolar-arterial oxygen tension difference, arterial hypoxemia, and decreased carbon monoxide 

diffusion capacity (Andrews et al. 1969; Johnson 1983; Rossman et al. 1988). A study by Pappas and 

Newman (1993) investigated whether early beryllium disease was also associated with impaired lung 

function. In this study, lung function test results from 21 “surveillance-identified” subjects (individuals 

with abnormal BeLPT results who did not seek medical attention prior to the diagnosis of beryllium 

sensitization) were compared with the results in 15 “clinically-identified” subjects (individuals who 

sought medical attention because of respiratory problems or abnormal x-rays). The lung function tests 

consisted of spirometry, lung volumes, diffusing capacity for carbon monoxide, arterial blood gases, and 

maximal exercise capacity. No alterations in spirometry, lung capacity, blood gases, or diffusing capacity 

were found in the surveillance-identified subjects. However, subtle alterations in exercise capacity were 

found in 52% of the surveillance-identified subjects, the most common effect was a rise in dead space to 

tidal volume ratio during exercise. In contrast, 93% of the clinically-identified subjects had alteration in 

lung function. The alterations included mild to moderate airway obstruction, evidence of restriction, 

abnormal resting blood gas analysis, and impaired exercise capacity (able to perform less work than 

surveillance-identified subjects). 

In animals, the respiratory system is also the primary target for inhalation exposure to beryllium. Rats 

exposed to 1–100 mg beryllium/m3

 as beryllium oxide (calcined at 1,000 EC) for 30–180 minutes had 

initial alveolar deposition of 1–63 μg beryllium in the lungs (Sanders et al. 1975). The exact exposure 

concentrations were not clearly specified. Rats developed only slight to moderate granulomatous lesions 

in the lungs, depending on the amount of alveolar deposition. Dust laden or degenerative macrophages 

and a moderate infiltration of lymphocytes were noted in the lungs of rats exposed to beryllium oxide. 

Hamsters, similarly exposed until an initial lung burden of 16–17 μg beryllium was achieved, developed 

only a few small areas of granuloma formation and degenerating macrophages. Pulmonary lavage fluid 

from rats exposed to 0.447 mg beryllium/m3

 as beryllium oxide (calcined at 560 EC) for 1 hour was 

examined at various intervals for #21 days after exposure for cell populations, acid and alkaline 

phosphatase enzyme activity of lysozyme and lactic dehydrogenase, and biochemical analysis of protein, 

lipid, phosphorus, phosphatidyl choline, and sialic acid (Hart et al. 1984). Microscopic examination of 

the cell populations revealed inflammation characterized by increased interstitial mononuclear cells and a 

thickening of the alveolar septa. Increases in the lipids and proteins and levels of acid and alkaline 

phosphatase, lysozyme, and lactic dehydrogenase indicated cellular damage to the type II cells or the 

alveolar epithelium. Similar analyses of rats exposed to $3.3 mg beryllium/m3

 and mice exposed to 
BERYLLIUM 55 

3. HEALTH EFFECTS 

7.2 mg beryllium/m3 as beryllium sulfate for 1 hour and examined for #12 months indicated the 

occurrence of pneumonitis with thickening of the alveolar walls and inflammation of the lung 

(Sendelbach et al. 1986, 1989; Sendelbach and Witschi 1987b). Increased levels of acid and alkaline 

phosphatase, and lactic dehydrogenase in the lavage fluid of the lungs of treated rats and mice indicated 

damage to the cellular populations; the increase in protein indicated alveolar damage. These studies 

demonstrate the ability of soluble beryllium compounds to damage the lung long after exposure ceases. 

Dogs exposed to 10 mg beryllium/m3

 as beryllium oxide calcined at 500 or 1,000 EC developed 

granulomas in the lung (Haley et al. 1989). Histopathology also revealed intense alveolar septal fibrosis 

and epithelial hyperplasia. Beryllium oxide calcined at 500 EC was associated with higher incidences of 

lesions, due to its greater solubility. Dogs exposed to 115 mg beryllium/m3

 as a mixture of beryllium 

oxide, beryllium fluoride, and beryllium chloride for 20 minutes, had inflamed lungs and granulomatous 

foci (Robinson et al. 1968). Increased lung weight, inflammation, emphysema, and fibrosis of the lung 

were observed in monkeys exposed to 0.198 mg beryllium/m3

 as beryllium sulfate for 7–17 days 

(Schepers 1964). Monkeys exposed to $13 mg beryllium/m3

 as beryllium hydrogen phosphate for 

8–10 days, and 0.184 mg beryllium/m3

 as beryllium fluoride for 7–18 days had severely inflamed and 

fibrotic lungs with granulomas. Histology revealed pleuritis, congestion, emphysema, consolidation, and 

edema of the lung. The severity of these effects was more notable with beryllium fluoride than with 

beryllium sulfate or beryllium hydrogen phosphate, partly due to the fluoride component which may form 

hydrofluoric acid in the lung as beryllium fluoride dissociates. Rats, rabbits, and guinea pigs exposed to 

31 mg beryllium/m3

 as beryllium oxide for 10 days did not have any histological evidence of lung 

damage (Hall et al. 1950). 

Animals exposed to beryllium compounds for intermediate durations had health effects similar to those 

caused by acute exposure. Rats and hamsters exposed to 0.21 mg beryllium/m3

 as bertrandite ore for 

6 months developed granulomatous lesions composed of several large, tightly packed, dust laden 

macrophages and a few lymphocytes (Wagner et al. 1969). However, when the rats were exposed to 

0.620 mg beryllium/m3

 as beryl ore, the lungs were largely unaffected except for a few small areas of 

atypical alveolar wall cell proliferation. Monkeys exposed to 0.210 or 0.620 mg beryllium/m3

 as 

bertrandite or beryl ore, respectively, had relatively minor changes in the lung. The changes observed 

were aggregates of dust-laden macrophages, lymphocytes, and plasma cells near respiratory bronchioles 

and small blood vessels. Vascular congestion, emphysema, and pneumonitis were observed during 

histological examination of the lungs of dogs exposed to 3.6 mg beryllium/m3

 as beryllium oxide for 

40 days or to 31 mg beryllium/m3

 as beryllium oxide for 17.5 days (Hall et al. 1950). Epithelialization of 

the alveoli, focal metaplasia, and granulomas were observed in rats exposed to beryllium sulfate for 
 

BERYLLIUM 56 

3. HEALTH EFFECTS 

6 months (Schepers et al. 1957); however, a nonexposure-related outbreak of pneumonia limits the 

interpretation of these results. Exposure of rabbits, dogs, cats, and monkeys to 0.04 mg beryllium/m3

 as 

beryllium sulfate for 100 days caused distortion of the lung structure (Stokinger et al. 1950). The lung 

appeared to be severely inflamed and emphysematous, resulting in an increase in dead air space. No 

respiratory effects were observed in rabbits, cats, and monkeys exposed to 30 mg beryllium/m3

 as 

beryllium oxide for 15 days; however, rats experienced respiratory distress (Hall et al. 1950). 

Chronic exposure to beryllium and its compounds causes similar health effects as those observed after 

shorter exposure durations. Hamsters and monkeys exposed chronically to 0.210 and 0.620 mg 

beryllium/m3

 as bertrandite or beryl ore, respectively, had relatively normal lung morphology, except that 

monkeys had inflamed lungs and hamsters exposed to the bertrandite ore had a few granulomatous lesions 

(Wagner et al. 1969). Rats exposed to 0.210 mg beryllium/m3

 as bertrandite ore had bronchial 

lymphocytic infiltrates, abscesses, consolidated lobes, and granulomatous lesions. Inflamed lungs and 

areas of fibrosis and granuloma were observed in rats exposed to 0.620 mg beryllium/m3

 as beryl ore. 

Proliferative responses of the alveolar epithelium were also observed. Although the beryllium exposure 

levels were fairly low in this study, the animals were exposed to 15 mg/m3

 of bertrandite ore or beryl ore, 

which was the TLV for inert dust. Additionally, the beryllium ores contained high levels of silica 

(approximately 64%). It is possible that the high dust and silica exposure levels may have contributed to 

the observed effects; it should be noted that silicosis was not observed. Rats exposed to levels as low as 

0.006 mg beryllium/m3

 as beryllium oxide had inflamed lungs and some fibrosis (Vorwald and Reeves 

1959). Chronic exposure of rats to other beryllium compounds caused health effects similar to those 

caused by beryllium oxide. Rats exposed to 0.034 mg beryllium/m3

 as beryllium sulfate for 72 weeks had 

inflamed lungs, emphysema, arteriolar wall thickening, granulomas, fibrosis, and proliferative responses 

within the alveoli (Reeves et al. 1967). Rats exposed to 0.0547 mg beryllium/m3

 as beryllium sulfate for 

6–18 months had inflamed lungs and fibrosis (Vorwald and Reeves 1959). 

Cardiovascular Effects. Data regarding the cardiovascular effects of beryllium and its compounds 

in humans are limited. Severe cases of chronic beryllium disease can result in cor pulmonale, which is 

hypertrophy of the right heart ventricle. In a case history study of 17 individuals exposed to beryllium in 

a plant that manufactured fluorescent lamps, autopsies revealed right atrial and ventricular hypertrophy 

(Hardy and Tabershaw 1946). An increase in deaths due to heart disease or ischemic heart disease was 

found in workers at a beryllium manufacturing facility (Ward et al. 1992). It is not likely that the cardiac 

effects are due to direct toxicity to the heart, but rather are a response to impaired lung function. 
 

BERYLLIUM 57 

3. HEALTH EFFECTS 

Heart enlargement was observed in monkeys after acute inhalation exposure to $13 mg beryllium/m3 as 

beryllium hydrogen phosphate, 0.184 mg beryllium/m3

 as beryllium fluoride, or 0.198 mg beryllium/m3 

as beryllium sulfate (Schepers 1964). Decreased arterial oxygen tension was observed in dogs exposed to 

30 mg beryllium/m3

 beryllium oxide for 15 days, 3.6 mg beryllium/m3 as beryllium oxide for 40 days 

(Hall et al. 1950), or 0.04 mg beryllium/m3

 as beryllium sulfate for 100 days (Stokinger et al. 1950). The 

effects of beryllium compounds on the cardiovascular system probably represent compensatory increases 

in cardiac musculature due to pulmonary fibrosis caused by inhalation exposure. The decrease of arterial 

oxygen tension reflects the reduced ability of the lung to oxygenate blood. 

Hematological Effects. Information regarding the hematological effects of beryllium and its 

compounds in humans is limited to case histories. No difference in white blood cell counts, hematocrit, 

or differential white blood cell percentages was observed in a machinist with chronic beryllium disease 

who worked with beryllium metal (Johnson 1983). A study involving 170 case histories of beryllium 

workers in the Cleveland area reported few differences in erythrocyte sedimentation rates, blood counts, 

or blood chemistry (VanOrdstrand et al. 1945). 

Acute exposure of animals to beryllium and its compounds had little effect on hematological parameters; 

however, intermediate-duration exposures caused anemia in several species. Hematological evaluation of 

rats and hamsters exposed to 1–100 mg beryllium/m3

 for 30–180 minutes to achieve initial alveolar 

deposition of 1–63 μg beryllium revealed no statistical difference between treated animals and controls 

(Sanders et al. 1975). The exact exposure concentration and duration were not clearly reported. 

Exposure to 31 mg beryllium/m3

 as beryllium oxide did not cause effects on the hematopoietic system in 

rats (Hall et al. 1950). No significant differences in leukocyte counts were observed in rabbits similarly 

exposed to beryllium oxide for 10 days. However, erythrocyte counts decreased slightly during the 

course of exposure. 

Rabbits exposed to 307 mg beryllium/m3

 as beryllium oxide for 60 days developed macrocytic anemia 

(Hall et al. 1950). The erythrocyte counts decreased over time, and there was a tendency to develop 

hypochromia, indicated by transient decreases in the average mean corpuscular hemoglobin 

concentration. Dogs exposed to 30 mg beryllium/m3

 as beryllium oxide for 15 days exhibited a moderate, 

progressive leukocytosis, while dogs exposed to 3.6 mg beryllium/m3

 for 40 days developed macrocytic 

anemia manifested as an increased mean corpuscular volume and decreased erythrocyte count. The bone 

marrow was almost exhausted. Differential counting of the bone marrow smears indicated a decrease in 

erythroblasts and an increase in normoblasts. Exposure to the more soluble compounds of beryllium 
 

BERYLLIUM 58 

3. HEALTH EFFECTS 

caused effects similar to those of beryllium oxide. Macrocytic anemia developed in rats and rabbits 

exposed to 0.43 mg beryllium/m3

 and dogs exposed to 0.04 mg beryllium/m3 as beryllium sulfate for 

100 days (Stokinger et al. 1950). Exposure to 2.0 and 0.43 mg beryllium/m3

 as beryllium sulfate in rats, 

rabbits, and dogs caused transient leukocytosis; exposure to 2.0 mg beryllium/m3

 caused mild 

thrombocytosis. With increasing exposure durations, dogs exposed to 0.04 mg beryllium/m3

 as beryllium 

sulfate had decreased phospholipid and cholesterol content of the red blood cells. The changes in the 

biochemical constituents of the red blood cells may reflect a toxic effect on erythropoietic processes in the 

bone marrow. 

Hematological effects were not observed in rats, hamsters, or monkeys exposed to 0.21 or 0.62 mg 

beryllium/m3

 as bertrandite or beryl ore, respectively, for 6–23 months (Wagner et al. 1969). 

Hepatic Effects. Information regarding hepatic effects in humans after inhalation exposure to 

beryllium and its compounds is limited. Following an accidental leakage of beryllium dust, 25 laboratory 

workers were exposed to an undetermined concentration of beryllium chloride over a period of 

10–20 hours (Zorn et al. 1986). During a 10-month follow-up, no increase was observed in liver 

enzymes, serum glutamic oxaloacetic transaminase, or serum glutamic pyruvic transaminase. In another 

study involving case histories of 17 individuals exposed to beryllium in a plant that manufactured 

fluorescent lamps, autopsy revealed hepatic necrosis in one individual (Hardy and Tabershaw 1946). 

Few hepatic effects have been observed in animals after inhalation exposure to beryllium and its 

compounds, except at lethal exposure levels. Acute exposure to $13 mg beryllium/m3

 as beryllium 

hydrogen phosphate causes hepatocellular degeneration in monkeys (Schepers 1964). Hepatocellular 

degeneration was also observed in monkeys exposed to 0.184 mg beryllium/m3

 as beryllium fluoride for 

7–18 days. These exposure levels were lethal to monkeys. Histological examination revealed no hepatic 

changes in rats, rabbits, guinea pigs or hamsters following acute inhalation exposure to either beryllium 

oxide or beryllium sulfate (Hall et al. 1950; Sanders et al. 1975). 

Intermediate-duration exposure of rats, monkeys, and hamsters to 0.210 and 0.620 mg beryllium/m3

 as 

bertrandite or beryl ore did not result in histological evidence of hepatic damage (Wagner et al. 1969). 

Decreases in serum protein concentration and the albumin/globulin ratio in the blood indicated that some 

liver damage occurred in dogs exposed to 3.6 mg beryllium/m3

 as beryllium oxide (Hall et al. 1950). Rats 

and dogs exposed to 2.0 and 0.04 mg beryllium/m3

 as beryllium sulfate, respectively, had increased serum 
 

BERYLLIUM 59 

3. HEALTH EFFECTS 

albumin and globulin levels (Stokinger et al. 1950). Histological examination of rats exposed to 

0.035 mg beryllium/m3

 as beryllium sulfate for 30 days revealed no hepatic damage (Schepers et al. 

1957). 

No adverse hepatic effects were revealed by histological examination or liver enzyme analysis of rats, 

hamsters, and monkeys chronically exposed to beryllium oxide as bertrandite or beryl ore (Wagner et al. 

1969). 

Renal Effects. Kidney stones were observed in .10% of the cases of chronic beryllium disease 

collected by the Beryllium Case Registry up to 1959 (Hall et al. 1959). In addition, an excess of calcium 

in the blood and urine has been seen quite frequently in patients with chronic beryllium disease. These 

effects are only suggestive and cannot be absolutely attributed to beryllium disease (Stoeckle et al. 1969). 

In a cohort mortality study of workers employed at beryllium manufacturing facilities, an increased risk 

of death from chronic and unspecified nephritis, renal failure, and other renal sclerosis was observed 

(Ward et al. 1992). 

Renal effects in animals after inhalation exposure to beryllium and its compounds are minor, except at 

lethal concentrations. No adverse renal effects were detected by urinalysis, kidney weight measurement, 

or histological examination in rats, rabbits, hamsters, and guinea pigs exposed to beryllium oxide for 

acute durations (Hall et al. 1950; Sanders et al. 1975). Guinea pigs, mice, hamsters, and rats exposed to 

4.3 mg beryllium/m3

 as beryllium sulfate had protein in the urine; however, there was no protein in the 

urine of similarly exposed rabbits (Stokinger et al. 1950). No other measures of renal integrity were 

conducted in this study. Histological examination revealed glomerular degeneration in the kidneys of 

monkeys exposed to 0.198 mg beryllium/m3

 as beryllium sulfate, 0.184 mg beryllium/m3 as beryllium 

fluoride, or $13 mg beryllium/m3

 as beryllium hydrogen phosphate (Schepers 1964). These 

concentrations were lethal to the monkeys. No histological evidence of renal damage was observed in 

rats exposed to 0.035 mg beryllium/m3

 as beryllium sulfate. 

Intermediate-duration exposure (6 months) of rats, hamsters, and monkeys to 0.210 or 0.620 mg 

beryllium/m3

 as bertrandite or beryl ore, respectively, did not result in evidence of renal effects during 

histological examination or enzyme analysis (Wagner et al. 1969). No renal effects were observed in 

dogs exposed to 31 mg beryllium/m3

 as beryllium oxide for #40 days. Urinary protein increased in dogs 

exposed to 0.43 mg beryllium/m3

 and rats exposed to 2.0 mg beryllium/m3 as beryllium sulfate for 

51–100 days (Stokinger et al. 1950). 
 

 

 

BERYLLIUM 60 

3. HEALTH EFFECTS 

No renal effects were identified by histological examination or enzyme analysis in rats, hamsters, and 

monkeys exposed for 12–17 months to 0.21 or 0.62 mg beryllium/m3

 as bertrandite or beryl ore (Wagner 

et al. 1969). 

Endocrine Effects. Evidence of the effects of beryllium and its compounds on the endocrine system 

has been observed in humans and animals. One out of 17 workers exposed to beryllium in a fluorescent 

lamp manufacturing plant died from chronic beryllium disease (Hardy and Tabershaw 1946). 

Histological examination of the adrenal glands revealed marked hyperemia and vacuolization. 

Effects on the adrenal gland have also been observed in animals exposed to beryllium compounds. 

Histological examination of monkeys exposed to 13 mg beryllium/m3

 as beryllium hydrogen phosphate or 

0.184 mg beryllium/m3

 as beryllium fluoride revealed marked hypoplasia and hypotrophy of the adrenal 

gland (Schepers 1964). However, the adrenal glands of monkeys exposed to 0.196 mg beryllium/m3

 as 

beryllium sulfate were normal. Rats and hamsters exposed to 1–100 mg beryllium/m3

 as beryllium oxide 

for 30–180 minutes had increased adrenal weight (Sanders et al. 1975). The exact exposure 

concentrations were not specified. 

Dermal Effects. Skin biopsies revealed granulomas containing beryllium in twins occupationally 

exposed to beryllium (McConnochie et al. 1988). Positive patch tests with soluble beryllium compounds 

were obtained in all 32 patients tested with known chronic beryllium disease, indicating that the patch test 

is useful in the diagnosis of chronic beryllium disease (Curtis 1959). However, the patch test using 

soluble beryllium compounds itself may be sensitizing and may exacerbate the condition in patients with 

chronic beryllium disease (Cotes et al. 1983; Epstein 1983; Stoeckle et al. 1969; Tepper 1972), 

contraindicating the use of patch testing in humans. 

Rats and guinea pigs exposed to 0.5 mg beryllium/m3

 as beryllium nitrate for 10 weeks had a typical 

delayed allergic reaction 24–48 hours after beryllium salts were applied to the skin (Stiefel et al. 1980). 

Ocular Effects. There is limited information on the ocular toxicity of beryllium. According to a case 

history, twins occupationally exposed to beryllium had reduced tear secretions (McConnochie et al. 

1988). 
 

BERYLLIUM 61 

3. HEALTH EFFECTS 

Body Weight Effects. Effects on body weight have been observed in humans after inhalation 

exposure to beryllium or its compounds. Weight loss was common among workers with acute beryllium 

disease (VanOrdstrand et al. 1945). Weight loss was also reported in workers at a fluorescent lamp 

manufacturing plant with chronic beryllium disease (Hardy and Tabershaw 1946). 

Weight loss, severe at times, has been observed in monkeys, rats, mice, dogs, and cats after acute-, 

intermediate-, and chronic-duration inhalation exposure to a variety of beryllium compounds. Due to 

impaired food consumption and “metabolic changes” (no additional information was provided), monkeys 

exposed for acute durations to $13 mg beryllium/m3

 as beryllium hydrogen phosphate for 8–10 days, 

0.184 mg beryllium/m3

 as beryllium fluoride for 7–18 days, or 0.198 mg beryllium/m3 as beryllium 

sulfate for 7 days lost 8–34, 19–23, or 24%, respectively, of their original body weight (Schepers 1964). 

Mice exposed to 4.3 mg beryllium/m3

 as beryllium sulfate for 14 days had a 13% decrease in body weight 

(Stokinger et al. 1950). Dogs exposed to 115 mg beryllium/m3

 as beryllium fluoride, beryllium oxide, 

and beryllium chloride for 20 minutes had transient weight loss the first 7 days after exposure (Robinson 

et al. 1968). No effect on body weight was observed in rabbits exposed to 31 mg beryllium/m3

 as 

beryllium oxide for 10 days (Hall et al. 1950). 

Most of the available information on the effect of beryllium on body weight following intermediateduration exposure comes from three studies that tested a variety of animal species. In monkeys, weight 

loss was seen following exposure to 0.198 mg beryllium/m3

 as beryllium phosphate for 30 days (Schepers 

1964), 30 mg beryllium/m3

 as beryllium oxide for 15 days (Hall et al. 1950), or 0.43 mg beryllium/m3 as 

beryllium sulfate for 51–100 days (Stokinger et al. 1950); but not in monkeys exposed to 0.620 mg 

beryllium/m3

 as beryllium oxide for 6 months (Wagner et al. 1969). The magnitude of weight loss ranged 

from 15 to 39%. A 3–9% weight loss was observed in rats exposed to 30 mg beryllium/m3

 as beryllium 

oxide for 15 days (Hall et al. 1950); however, a series of studies by Wagner et al. (1969) did not find any 

alterations in body weight gain in rats exposed to 0.210 or 0.620 mg beryllium/m3

 as beryllium oxide. 

This study also did not find body weight alterations in hamsters exposed to the same concentrations of 

beryllium oxide. Weight loss was also observed in dogs exposed to 3.6 or 30 mg beryllium/m3

 as 

beryllium oxide for 40 or 15 days, respectively (Hall et al. 1950) or 0.4 mg beryllium/m3

 as beryllium 

sulfate for 51–100 days (Stokinger et al. 1950). Severe weight loss was also observed in cats exposed to 

0.04 mg beryllium/m3

 as beryllium sulfate for 51–100 days (Stokinger et al. 1950) or 30 mg beryllium/m3 

as beryllium oxide for 15 days (Hall et al. 1950). No effect was observed in rabbits exposed to 0.04 mg 

beryllium/m3

 as beryllium oxide for 30 days or 2.0 mg beryllium/m3 as beryllium sulfate for 51–100 days 

(Stokinger et al. 1950). 
BERYLLIUM 62 

3. HEALTH EFFECTS 

Exposure to 0.034 mg beryllium/m3 as beryllium sulfate for 72 weeks caused more severe body weight 

loss among female rats than among males (Reeves et al. 1967). Rats exposed to 0.62 mg beryllium/m3

 as 

beryl ore for 17 months also had significantly reduced body weights, compared to controls (Wagner et al. 

1969). 

3.2.1.3 Immunological and Lymphoreticular Effects 

While acute beryllium disease is a chemical pneumonitis, chronic beryllium disease appears to be an 

immunological disease. The evidence that chronic beryllium disease is an immunological disease is 

supported by the following. Beryllium can induce classic cell-mediated immune responses in humans and 

animals (Barna et al. 1981, 1984; Curtis 1951, 1959; Epstein et al. 1982; Haley et al. 1989; Marx and 

Burrell 1973; Saltini et al. 1989, 1990; Stiefel et al. 1980). Beryllium sensitized cells accumulate at sites 

of chronic beryllium disease, resulting in granulomas in the lungs (Rossman et al. 1988; Saltini et al. 

1989, 1990). Beryllium has been identified within the granulomas of patients with chronic beryllium 

disease (Williams and Kelland 1986). Virtually all patients with chronic beryllium disease have a cellmediated immune response to beryllium (Rossman et al. 1988; Saltini et al. 1989), and therapy that 

controls the immune response (i.e., corticosteroids) can ameliorate the disease (Aronchick et al. 1987). 

Nonspecific immunologic findings in chronic beryllium disease include an increase in serum gammaglobulin levels (Resnick et al. 1970). The existence of specific antibodies to beryllium have been 

reported (Clarke 1991), and further research to confirm and identify the antibodies is continuing. 

While the results of peripheral blood lymphocyte proliferative responses to beryllium have been variable 

in patients with chronic beryllium disease (Kreiss et al. 1989; Newman et al. 1989; Saltini et al. 1989; 

Stokes and Rossman 1991; Williams and Williams 1983), the results of lung lymphocyte proliferative 

responses to beryllium have been consistently positive (Rossman et al. 1988; Saltini et al. 1989). 

Lung lavage studies in patients with chronic beryllium disease have revealed that there is an accumulation 

of CD4+T cells in the lungs (Rossman et al. 1988) and that these cells are memory T cells (Saltini et al. 

1989). Antibodies to Class II antigens but not Class I antigens will block the beryllium-specific 

proliferative response. In addition, antibodies to the IL-2 receptor will also block the beryllium 

proliferative response. 
BERYLLIUM 63 

3. HEALTH EFFECTS 

Immunological effects have also been observed in animals after inhalation exposure to beryllium. Dogs 

exposed to 10 mg beryllium/m3

 as beryllium oxide had a greater immune response to beryllium oxide 

calcined at 500 EC than at 1,000 EC, due to the greater solubility of the 500 EC calcined beryllium oxide 

(Haley et al. 1989). The dogs exposed to beryllium oxide calcined at 500 EC had higher cell counts in the 

bronchoalveolar lavage fluid as a result of an increased lymphocyte population. There was also a greater 

response of pulmonary lymphocytes in vitro to beryllium salts. The tracheobronchial lymph nodes had 

moderate cortical and paracortical lymphoid hyperplasia resulting from B and T cell activation. The 

lymph nodes examined 365 days after treatment were characterized by lymphoid depletion, marked 

congestion, and medullary fibrosis. Histological examination of monkeys exposed for 8–10 days to 

$13 mg beryllium/m3

 or for 30 days to 0.198 mg beryllium/m3 as beryllium hydrogen phosphate revealed 

hypoplasia of the lymph nodes (Schepers 1964). The hypoplasia may be a result of the nutritional status 

of the animal since most of the monkeys lost body weight and were anorexic. Histological examination 

of monkeys exposed for 7–18 days to either 0.198 or 0.184 mg beryllium/m3

 as beryllium sulfate or 

beryllium fluoride, respectively, revealed marked hyperplasia of the lymph nodes, typical of immune 

activation. On the other hand, exposure of rats to 0.035 mg beryllium/m3

 as beryllium sulfate for <7 or 

30 days did not cause histopathological changes in the suprarenal, pulmonary, or hepatic lymph nodes 

(Schepers et al. 1957); the high incidence on non-exposure-related pneumonia limits the interpretation of 

this study. 

Similar immunological effects have been observed in animals exposed to beryllium for intermediate 

durations. Rats and guinea pigs exposed to 0.5 mg beryllium/m3

 as beryllium nitrate for 10 weeks had 

inflammations typical of delayed hypersensitivity, as assessed by skin tests and lymphocyte proliferation 

tests (Stiefel et al. 1980). Lymphocytes exposed in vitro to beryllium salts had increased proliferation 

rates greater than those of the controls. Gross and histological examination of the thymus and spleen of 

rats, hamsters, and monkeys exposed to 0.21 or 0.62 mg beryllium/m3

 as bertrandite or beryl ore, 

respectively, for 6–23 months revealed no pathological alterations (Wagner et al. 1969). 

The highest NOAEL values and all reliable LOAEL values for immunological effects in each species and 

duration category are recorded in Table 3-1 and plotted in Figure 3-1. 
BERYLLIUM 64 

3. HEALTH EFFECTS 

3.2.1.4 Neurological Effects 

No studies were located regarding neurological effects in humans or animals after inhalation exposure to 

beryllium or its compounds. 

3.2.1.5 Reproductive Effects 

No studies were located regarding reproductive effects in humans or animals after inhalation exposure to 

beryllium or its compounds. Male and female rats were intratracheally injected with 0.6 mg beryllium/kg 

as radioactive beryllium oxide and allowed to mate over a 15-month period (Clary et al. 1975). There 

were no consistent effects on reproductive performance as determined by the average number of 

pregnancies per female, live pups per litter, dead pups per litter, live pups per female, lactation index, or 

average weight of live pups per female. 

3.2.1.6 Developmental Effects 

No studies were located regarding developmental effects in humans or animals after inhalation exposure to 

beryllium or its compounds. A study conducted by Selivanova and Savinova (1986) examined the 

developmental toxicity of 50 mg beryllium/kg as beryllium chloride and beryllium oxide administered via 

intratracheal injection on gestational days 3, 5, 8, or 20. An increase in fetal mortality was observed in rats 

dosed on gestational day 3 with beryllium oxide and in rats dosed on gestational day 5 with either beryllium 

compound. Exposure to beryllium oxide or beryllium chloride on gestational day 3 resulted in decreased 

fetal body weights and an increased percentage of pups with internal abnormalities. The latter effect was 

also observed in the pups of rats exposed to beryllium chloride or beryllium oxide on gestational day 5 and 

beryllium oxide on gestational day 8. There were no differences in the number of live births per dam or in 

fetal length. 
BERYLLIUM 65 

3. HEALTH EFFECTS 

3.2.1.7 Cancer 

A number of retrospective cohort mortality studies examining workers at beryllium processing facilities in 

Pennsylvania and Ohio have been conducted by Mancuso and Associate (Mancuso 1970, 1979, 1980; 

Mancuso and El-Attar 1969) and the National Institute of Occupational Safety and Health (NIOSH) (Bayliss 

et al. 1971; Sanderson et al. 2001a; Wagoner et al. 1980; Ward et al. 1992); many of these studies examined 

one or two facilities and others looked at seven facilities. One of the earliest cancer mortality studies of these 

workers was conducted by Mancuso and El-Attar (1969). This study examined a cohort of 3,685 Caucasian 

male workers employed at two beryllium facilities in Ohio and Pennsylvania from 1937 to 1948; the cohort 

was followed through 1966. Social Security Administration data, Beryllium Registry data, and death 

certificates were used to identify employees, deaths, and causes of death. A group of workers in the rubber 

industry were used as a control group (no additional information on this cohort was provided). The study 

authors note that a “slightly higher” rate of deaths from malignant neoplasms of the lung, trachea, and 

bronchus were observed in the beryllium workers; no statistical analyses of the data were conducted. 

Interpretation of these data is limited by the inclusion of nonexposed workers (no data were available on 

which departments the workers were employed in), lack of information on exposure characterization, 

incomplete reporting of deaths or cause of death, large employee turnover rate (78% of the workers were 

employed for <2 years), and lack of statistical analysis. An additional limitation of the study is the selection 

of rubber workers as the comparison group, as increased incidence of lung cancer has been found in other 

studies of rubber workers (Mancuso 1979). 

In the second phase of the cohort mortality study (Mancuso 1970), duration of employment and age as of 

1940 were considered and the observation period was extended to 1967. The small number of deaths in each 

duration category, as well as the limitations discussed above in the Mancuso and El-Attar (1969) study, 

precludes drawing conclusions from this study. A third study by this group (Mancuso 1979) restricted 

the cohort to workers employed during the period of 1942–1948, extended the observation period to 

1974 for the Ohio cohort and 1975 for the Pennsylvania cohort, and compared mortality in the beryllium 

workers to mortality for the U.S. white male population (using vital statistics data for the period ending in 

1967). An increase in the number of lung cancer deaths was observed in workers with a latency period of 

15 years or higher (22 observed versus 9.86 expected in the Ohio cohort and 36 observed versus 

22.02 expected in the Pennsylvania cohort); the study author notes that the differences are statistically 

significant. EPA (1987) and MacMahon (1994) have criticized this study. In particular, EPA (1987) 

notes that using U.S. white male lung cancer death rates for the period ending in 1967 to estimate 

expected cases for 1968–1975 resulted in a 10–11% underestimation of expected lung cancer deaths 
BERYLLIUM 66 

3. HEALTH EFFECTS 

because nationwide lung cancer rates were increasing. EPA (1987) and MacMahon (1994) comment that 

Mancuso (1979) did not account for the potential confounding effect of cigarette smoking on lung cancer 

mortality. 

To determine whether the increased lung cancer deaths that have been observed in the previous papers by 

Mancuso and Associate (Mancuso 1970, 1979; Mancuso and El-Attar 1969) were due to beryllium 

exposure, or the excess risk could be attributed to personal characteristics of workers having unstable 

employment patterns, Mancuso (1980) conducted a fourth study of the Ohio and Pennsylvania cohorts 

followed through 1976. Employees in the viscose rayon industry served as a comparison group. A 

significant increase in lung cancer deaths was observed in the beryllium workers when compared to the 

entire cohort of rayon workers (standardized mortality ratio [SMR]=140) or a subcohort of workers who 

did not transfer between departments during their employment in the viscose rayon industry (SMR=158). 

When the cohorts were divided into employment durations, significant increases in lung cancer deaths 

were observed in the workers employed for <12 months (SMRs=138 and 164 for total rayon cohort and 

those not transferring departments, respectively) and workers employed for >49 months (SMRs=222 and 

172, respectively), but not in workers employed for 13–48 months. As with the other Mancuso studies, 

the design of this study has been criticized. One limitation of this study is the lack of adjustment for the 

potential confounding effect of smoking. EPA (1987) questioned whether there was an adjustment for 

potential age differences between the beryllium cohort and noted that NIOSH re-analyzed the data from 

this study and found “serious problems with Mancuso’s analysis”. 

NIOSH studies have examined workers at the same facilities as Mancuso, as well as several other 

beryllium processing facilities. The study by Bayliss et al. (1971) examined workers at a number of 

beryllium processing facilities in Ohio and Pennsylvania. The original cohort consisted of over 

10,000 male and female workers who had employment of at least a few days or longer in the beryllium 

industry. Removal of approximately 2,000 workers with inadequate records and all female workers 

(approximately 1,100 workers) resulted in a study cohort of approximately 7,000 workers. The number 

of deaths among the beryllium workers was lower than expected (SMR=92.2), which was attributed to a 

healthy worker effect. An increased number of deaths due to lung cancer was observed in the beryllium 

workers (SMR=105.7), but the increase was not statistically significant. Limitations of this study include 

lack of analysis for potential effect of latency, elimination of over 2,000 workers due to incomplete 

records, and the combining of populations from several different plants into one cohort (EPA 1987; 

MacMahon 1994). 
BERYLLIUM 67 

3. HEALTH EFFECTS 

A subsequent study sponsored by NIOSH and the Occupational Safety and Health Administration 

(OSHA) (Wagoner et al. 1980) examined beryllium workers at one facility in Reading, Pennsylvania. 

The study cohort of 3,055 white males employed between 1942 and 1967 were followed through 1975, 

and mortality rates were compared to the U.S. white male population (using NIOSH vital statistics data 

for the period ending in 1967). A significant increase in lung cancer deaths (47 observed versus 

34.29 expected) was observed in the beryllium workers. When deaths from lung cancer were segregated 

by latency period, significant increases in lung cancer deaths were found in workers with a latency period 

of at least 25 years (20 observed versus 10.79 expected); significant increases in lung cancer deaths were 

also observed in workers employed for <5 years and a latency period of at least 25 years (17 observed 

versus 9.07 expected). To assess the influence of lowering beryllium exposure concentrations, lung 

cancer deaths were segregated by date of initial employment. A significant increase in lung cancer deaths 

was observed in workers initially hired before 1950 (when strict beryllium controls were instituted) and a 

25-year or higher latency period (20 observed versus 10.76 expected). An increase in lung cancer deaths 

was also observed in workers initially employed after 1950, across latency periods, but the difference was 

not statistically significant (7 observed versus 4.60 expected). The study authors note that using national 

mortality rates probably resulted in a 19% underestimation of cancer risk because Berks County, 

Pennsylvania (where 87% of the workers resided) has a lower age-adjusted lung cancer rate than the U.S. 

general population (31.8 per 100,000 versus 38.0 per 100,000). However, EPA (1987) notes that most of 

the beryllium workers residing in Berks County lived in the city of Reading, Pennsylvania with a lung 

cancer mortality rate 12% higher than the national rate. Thus, using the national rates may have resulted 

in an underestimation of expected deaths. Wagoner et al. (1980) attempted to account for the contribution 

of cigarette smoking to lung cancer deaths by comparing smoking histories of the beryllium cohort 

(obtained during a 1968 medical survey) with U.S. white male smoking history (obtained by the 

1964–1965 Health Interview Survey conducted by the Public Health Service). Using these data, the study 

authors estimated that the smoking habits of the beryllium workers would result in a 14% higher risk of 

lung cancer than the comparison population. The study authors note that the frequency of cigarette 

smoking and the distribution of lung cancer cell type distribution support the conclusion that it is unlikely 

that “cigarette smoking per se could account for the increased risk of lung cancer among berylliumexposed workers in this study.” EPA (1987), MacMahon (1994), and Bayliss (1980) have discussed a 

number of severe limitations of this study: (1) using male mortality data for the period of 

1941–1967 resulted in a 10–11% underestimation of expected lung cancer deaths, (2) the influence of 

cigarette smoking was probably underestimated by the study authors, EPA estimated that differences in 

cigarette smoking patterns would result in a 4.6–18.8% underestimation of expected deaths, and (3) the 

inclusion of one individual who died of lung cancer but did not work at the beryllium facility because he 
BERYLLIUM 68 

3. HEALTH EFFECTS 

failed the pre-employment physical. After adjusting for use of outdated mortality data and cigarette 

smoking, EPA (1987) estimated that the rightful omission of this worker would result in a nonstatistically 

significant association between beryllium exposure and lung cancer mortality (46 observed versus 

41.90 expected deaths for all workers and 20 observed and 14.67 expected deaths for workers with a 

$2 year latency period). 

In a more recent study, Ward et al. (1992) examined mortality data for a cohort of 9,225 male workers 

employed at seven beryllium processing facilities in Ohio and Pennsylvania for at least 2 days in the 

period of 1940–1969; the workers were followed through 1988. Mortality rates in the beryllium cohort 

were compared to the U.S. white male population. Mortality from all causes was slightly elevated among 

the beryllium workers (SMR=1.05; 95% CI=1.01–1.08). The elevated mortality rate was largely due to 

increases in respiratory tract cancer, nonmalignant respiratory disease, and deaths from ischemic heart 

disease. The SMRs for trachea, bronchii, and lung cancer, nonmalignant respiratory disease, and 

ischemic heart disease were 1.26 (95% CI=1.12–1.42), 1.21 (95% CI=1.06–1.38), and 1.08 (95% 

CI=1.01–1.14), respectively. Analysis of mortality data for each individual plant revealed that significant 

increases in lung cancer deaths were only found in two facilities: Lorain, Ohio (SMR=1.69) and Reading, 

Pennsylvania (SMR=1.24). To assess the effect of duration of exposure and latency on lung cancer 

mortality, the total cohort and the Lorain and Reading cohorts were divided into several latency and 

duration of employment category. For the total cohort, duration of employment was not associated with 

increased lung cancer deaths, but increased latency was associated with increased lung cancer deaths. In 

the total cohort, statistically significant increases in lung cancer deaths were observed in the >30 year 

latency category (SMR=1.46), workers employed for <1 year with a >30 year latency (SMR=1.52), and in 

the 25–30 year latency period for workers employed for <1 year. Among workers at the Lorain and 

Reading facilities, significant increases in cancer mortality were also observed in workers employed for 

<1 year with a 30-year latency (SMRs=1.68 and 1.42, respectively). The decade of hire also influenced 

lung cancer deaths; this was independent of potential latency. The highest cancer mortality rates were 

observed among workers hired before 1950. Three of the seven beryllium-processing facilities were open 

in the 1940s; elevated cancer risks were observed at two of the facilities: Lorain (SMR=1.69; 95% 

CI=1.28–2.19) and Reading (SMR=1.26; 95% CI=1.02–1.56). The cancer risk was not significantly 

elevated in the plants operating during the 1950s or 1960s (the Lorain plant closed in 1948). The study 

authors also examined the influence of geographic variation in lung cancer mortality by comparing cancer 

mortality in the cohort with county lung cancer data. This comparison did not change the overall 

conclusions of the study. As with the Wagoner et al. (1980) study, Ward et al. (1992) used smoking habit 

data available from a 1968 Public Health Survey (included approximately 16% of cohort and four 
 

BERYLLIUM 69 

3. HEALTH EFFECTS 

facilities [including the Reading, Pennsylvania facility]) to account for this confounding variable. A 

smoking adjustment factor of 1.1323 was estimated using the available data on the beryllium cohort and 

smoking habit data for the U.S. population (obtained from the National Center for Health Statistics, 1965 

and Office of Health, Research, Statistics, and Technology, 1970). The smoking-adjusted SMRs for the 

entire cohort, the Reading cohort, and the Lorain cohort are 1.12, 1.09, and 1.49, respectively. 

As a follow-up to this study, Sanderson et al. (2001a) conducted a case control study using workers from 

the Reading, Pennsylvania facility. The study consisted of 142 lung cancer cases and 5 age-race matched 

controls for each lung cancer case. Three quantitative exposure metrics were used to estimate beryllium 

exposure levels: cumulative beryllium exposure, average beryllium exposure level, and maximum 

exposure level. Cumulative beryllium exposure was calculated by summing the products of the number 

of days a worker held a particular job times the estimated annual average beryllium exposure for the job 

on those specific days. Average beryllium exposure was calculated by dividing the cumulative exposure 

level by the number of days the worker was employed. The maximum exposure level was the highest 

time-weighted average (TWA) exposure of any job the worker held, regardless of duration. As described 

in a companion paper (Sanderson et al. 2001b), historical measurements were estimated using actual 

industrial hygiene measurements and extrapolations from existing measurements over time and across 

jobs. No industrial hygiene measurements were available before 1947. Data from 1947 to 1960 were 

used to estimate exposure during the period of 1935 to 1960 based on the assumption that exposure levels 

remained constant during this time period. When job-specific exposure levels were not available, 

measurements from other areas of the facility that were expected to have similar types of exposures were 

used as surrogates. No measurements were available for general laborers, maintenance workers, or 

salaried personnel (e.g., managers, engineers, office workers). Exposure levels for the general laborers 

and maintenance workers were estimated by averaging exposure estimates for a variety of jobs. For the 

salaried personnel, the exposure levels were estimated using measured data for janitors. The overall lung 

cancer mortality rate for the Reading plant through 1992 was 1.22 (95% CI=1.03–1.43), which is slightly 

lower than the mortality rate of this cohort through 1988 (see discussion of the Ward et al. 1992 study). 

Most of the cases and controls (approximately 60%) were hired during the 1940s when beryllium levels 

were uncontrolled. The average duration of employment was 3.7 years for the cases and 5.5 years for the 

controls; however, approximately 67 and 50% of the cases and controls, respectively, were employed for 

<1 year. The difference in employment duration was statistically significant. As compared to controls, a 

higher percentage of cases worked as general labor or maintenance departments where some of the 

highest beryllium exposures occurred; the difference was statistically significant when tenure was lagged 

10 or 20 years to discount exposures that may not have contributed to causing cancer because they 
BERYLLIUM 70 

3. HEALTH EFFECTS 

occurred after cancer induction. Cumulative, average, and maximum exposure levels were 4,606 μg/m3 

days, 22.8 μg/m3, and 32.4 μg/m3, respectively, for the cases and 6,328 μg/m3 days, 19.3 μg/m3, and 

27.1 μg/m3

 for the controls; the differences between the two groups was not statistically significant. 

However, when the exposure was lagged 10 or 20 years, the exposure levels were significantly higher 

among the cases. Cumulative beryllium exposure levels were 4,057 and 2,036 μg/m3

 days for the cases 

and controls, respectively, when lagged 10 years and 844 and 305 μg/m3

 days, respectively, when lagged 

20 years. Average exposure levels for the cases and controls were 22.6 and 12.3 μg/m3

, respectively, 

when lagged 10 years and 10.2 and 5.3 μg/m3

 respectively, when lagged 20 years. The maximum 

exposure levels were 30.8 and 16.1 μg/m3

 for the cases and controls, respectively, when lagged 10 years 

and 13..1 and 6.5 μg/m3

 when lagged 20 years. Significantly elevated odds ratios were observed in three 

highest quartiles (when compared to the first quartile) of average exposure and maximum exposure when 

exposure was lagged for 10 or 20 years, but not when unadjusted exposure levels were used. The odds 

ratios were significantly elevated in the three highest quartiles of maximum exposure when exposure was 

lagged 20 years and in the highest quartile of unadjusted maximum exposure. Similarly, significantly 

elevated odds ratios were found when the average and maximum exposure levels were divided into three 

categories (#2, >2-20, and >20 μg/m3

) when the exposure was lagged 10 or 20 years. In general, no 

significant relationship between duration of employment and cancer risk were found. Sanderson et al. 

(2001a) also attempted to address two potential confounding variables: cigarette smoking and exposure to 

other chemicals. The workers were potentially exposed to a number of other chemicals including nitric 

acid aerosols, aluminum, cadmium, copper, fluorides, nickel, and welding fumes. Significant odds ratios 

were found for copper and fluorides when exposure was lagged 10 or 20 years. Interpretation of this 

finding is difficult because there were no workers exposed to fluorides or copper only and exposure to 

fluorides and copper was highly associated with exposure to several beryllium compounds. Smoking 

history was only available for a small number of cases and controls. Thus, the study authors used an 

indirect method for assess the possible association between smoking status and cancer risk. The authors 

noted that in order for smoking to be a confounding variable, there would have to be an association 

between smoking status and beryllium exposure level; such an association was not found. 

In addition to these retrospective mortality studies of beryllium workers, there are two epidemiology 

studies of Beryllium Case Registry enrollees (Infante et al. 1980; Steenland and Ward 1992). In the 

Infante et al. (1980) study, a cohort of 421 white male workers entered into the Beryllium Case Registry 

(BCR) between July 1952 and December 1975; the cohort consisted of workers in the beryllium 

extraction and smelting, metal production, and fluorescent tube production industries and individuals not 

exposed occupationally but living near a beryllium facility. Mortality rates were compared to the U.S. 
BERYLLIUM 71 

3. HEALTH EFFECTS 

white male population for the period lung cancer (which includes trachea and bronchii cancers) was 

observed (7 observed compared to 2.81 expected), but the difference was not statistically significant. 

When the lung cancer rate was determined from workers with previously diagnosed respiratory problems, 

the number of observed deaths was 6 versus 1.91 expected (p<0.05). As with the Mancuso (1979) and the 

Wagoner et al. (1980) studies, using lung cancer mortality data for the period ending in 1967 probably 

resulted in a 10–11% underestimation of the number of expected deaths. The contribution of cigarette 

smoking to the observed increase in lung cancer deaths was not adjusted for because no smoking data 

were available for the cohort; the study authors note that it is unlikely that individuals with acute 

beryllium illness had smoking habits of sufficient magnitude to account for the excessive lung cancer risk 

in this group. 

A follow-up of the study by Infante et al. (1980) included female workers in the analysis and extended the 

follow-up period by 13 years to 1988 (Steenland and Ward 1992). The cohort consisted of 689 patients, 

66% of which were men. Of the entire cohort, 34% had been diagnosed with acute beryllium disease and 

64% with chronic beryllium disease (2% of the subjects had unknown disease type). The mortality rates 

due to specific causes were compared with that of the U.S. population after stratification by age, race, sex, 

and calendar time. Increases in mortality were observed among the beryllium workers; the primary cause 

of death was pneumoconiosis and other respiratory diseases (SMR=34.23; 95% CI=29.1–40.0), followed 

by deaths from beryllium poisonings (SMR=34.93; 95% CI=19.1–61.4), all cancers (1.51; 95% 

CI=1.17–1.91), and lung cancer (SMR=2.00; 95% CI=1.33–2.89). There were 70 deaths from all types of 

cancer, 28 of which were due to lung cancer. Of these, 22 lung cancer deaths occurred in men 

(SMR=1.76, 95% CI=1.02–2.67), and 6 occurred in women (SMR=4.04, 95% CI=1.47–8.81). No trend 

was found for duration of exposure or for time since initial exposure. The lung cancer excess was more 

pronounced among those with acute beryllium disease (SMR=2.32; 95% CI=1.35–3.72) than those with 

chronic beryllium disease (SMR=1.57; 95% CI=0.75–2.89). Data on smoking status were available for 

141 men and 82 women, and data on amount smoked were available for 51 men and 16 women. Analysis 

showed that the cohort smoked less than the U.S. population, and there were more former smokers and 

fewer current smokers in the cohort than in the U.S. population. Thus, the study authors concluded that 

the lung cancer excess was probably not due to smoking; the study authors also ruled out selection bias, 

concluding that excess exposure to beryllium was the causative factor. It is also possible that the 

beryllium disease process (particularly the acute disease) contributes to the development of lung cancer. 

In general, the early (prior to 1987) studies that associated beryllium exposure with lung cancer have been 

inadequately controlled for confounding factors such as smoking, improperly calculated expected deaths 
BERYLLIUM 72 

3. HEALTH EFFECTS 

from lung cancer, included employees in the beryllium industry who were not actually exposed to 

beryllium (e.g., salesmen, clerks), or used inappropriate controls. The more recent studies by Ward et al. 

(1992), Steenland and Ward (1992), and Sanderson et al. (2001a) have addressed many of these issues 

and provide strong data on the carcinogenic potential of beryllium in humans. NTP (1999, 2002) and 

IARC (2001) have concluded that beryllium is a human carcinogen; EPA (IRIS 2002) classified it as a 

probably human carcinogen (group B1). IARC (2001) noted that several aspects of the Ward et al. (1992) 

and Steenland and Ward (1992) studies support the conclusion that beryllium is a human carcinogen. In 

particular IARC noted (a) the consistency of lung cancer excess in most of the locations, (b) greater 

excess cancer risk in workers hired prior to 1950 when beryllium levels were much higher than in 

subsequent decades, and (c) the highest risk of lung cancer in individuals with acute beryllium disease 

and at the facility with the greatest proportion of acute beryllium disease. However, IARC (2001) also 

noted a number of limitations with the existing cancer database. The limitations include poor exposure 

characterization, relatively low excess cancer risk, and the lack of discussion of exposure to other lung 

carcinogens. Additionally, several reviewers have criticized the conclusions of the Steenland and Ward 

(1992) and Ward et al. (1992) studies. In general, the criticism focuses on the relatively low excess of 

cancer risk and the inadequate adjustment for smoking habits (Eisenbud 1993, 1997; Kolanz 2001; Kotin 

1994; MacMahon 1994; Trichopoulos 2000). Using the data from the Ward et al. (1992) study, Levy et 

al. (n.d.) recalculated the SMRs for lung cancer using city mortality rates rather than county or U.S. rates 

and a different indirect method for adjusting for smoking and did not find significant increases in the 

incidence of lung cancer among beryllium workers. A meta-analysis of the data did find a significant 

increase in lung cancer risk, although the SMRs were lower than those calculated by Ward et al. (1992). 

Some beryllium compounds are carcinogenic in animals exposed via inhalation. A single nose-only 

exposure to 410–980 mg/m3

 beryllium metal aerosol for 8–48 minutes resulted in a 64% incidence of lung 

tumors in rats; lung tumors were first observed 14 months after exposure (Nickell-Brady et al. 1994). 

Rats exposed to 0.035 mg beryllium/m3

 as beryllium sulfate for 180 days had increased lung cancer rates, 

compared to controls (Schepers et al. 1957). 

Cancer incidence was not increased in hamsters exposed to 0.21 or 0.62 mg beryllium/m3

 as bertrandite or 

beryl ore for chronic durations (Wagner et al. 1969). In addition, rats similarly exposed to bertrandite ore 

did not have a greater incidence of lung cancer than that observed in the controls. However, 18 of 19 rats 

exposed to 0.62 mg beryllium/m3

 as beryl ore developed tumors that were classified as bronchial alveolar 

cell tumors, adenomas, adenocarcinomas, or epidermoid tumors. Primary pulmonary cancer of the 

bronchiole was observed at 9 months in rats exposed to 0.006 or 0.0547 mg beryllium/m3

 as beryllium 
BERYLLIUM 73 

3. HEALTH EFFECTS 

oxide (Vorwald and Reeves 1959). The rats were examined for signs of cancer at 6, 9, 12, and 

18 months. Lung tumors, which appeared to be adenocarcinomas with a predominantly alveolar pattern, 

were observed after 13 months of exposure in 100% of rats exposed to 0.034 mg beryllium/m3

 as 

beryllium sulfate (Reeves et al. 1967). Monkeys exposed to 0.035 mg beryllium/m3

 as beryllium sulfate 

had tumors in the hilus and peripheral portions of the lung, and scattered throughout the pulmonary tissue, 

as determined by histological examination (Vorwald 1968). Moreover, there were extensive metastases 

to the mediastinal lymph nodes and to other areas of the body. It should be noted that many of the studies 

conducted in animals have been criticized because of poor documentation, being conducted at single dose 

levels, or failure to include controls (EPA 1987). However, collectively, the animal data indicate that 

beryllium is carcinogenic in animals. 

The CELs in each species are recorded in Table 3-1 and plotted in Figure 3-1. 

3.2.2 Oral Exposure 
BERYLLIUM 74 

3. HEALTH EFFECTS 

3.2.2.1 Death 

No studies were located regarding death in humans after oral exposure to beryllium or its compounds. 

Oral LD50 values in animals vary according to the compound. LD50 values for beryllium sulfate were 

120 mg beryllium/kg in rats (Lanchow University 1978) and 140 mg beryllium/kg in mice (Ashby et al. 

1990). The LD50 values for beryllium chloride in rats were 200 mg beryllium/kg (Kimmerle 1966). The 

LD50 values for beryllium fluoride were 18–20 mg beryllium/kg in mice (Kimmerle 1966; Lanchow 

1978). The LD50 value for beryllium oxyfluoride was 18.3 mg beryllium/kg in rats. The additional 

toxicity of the fluoride ion accounted for the lower LD50 value observed for beryllium fluoride and 

beryllium oxyfluoride. The difference in the LD50 values for the other beryllium compounds is due to 

differences in solubility and the potential to form insoluble beryllium phosphate in the gastrointestinal 

tract. 

Increased mortality was observed in dogs exposed to 12 mg beryllium/kg/day as beryllium sulfate in the 

diet; the likely cause of death was severe ulcerative lesions in the gastrointestinal tract (Morgareidge et al. 

1976). In chronic studies, no effect on survival was observed in rats and dogs exposed to #31 or 1 mg 

beryllium/kg/day, respectively, as beryllium sulfate in the diet (Morgareidge et al. 1975, 1976) or in rats 

and mice exposed to 0.6–0.7 or 1 mg beryllium/kg/day, respectively, as beryllium sulfate in drinking 

water (Schroeder and Mitchener 1975a, 1975b). 

The LD50 values in rats and mice and doses associated with increased mortality in dogs are recorded in 

Table 3-2 and plotted in Figure 3-2. 

3.2.2.2 Systemic Effects 

No studies were located regarding respiratory, cardiovascular, gastrointestinal, hematological, 

musculoskeletal, hepatic, renal, or dermal, and ocular effects in humans after oral exposure to beryllium 

or its compounds. The systemic effects observed in animals after oral exposure to beryllium compounds 

are discussed below. 
a Key to 

figure 

Species 

(Strain) 

Exposure/ 

Duration/ 

Frequency 

(Specific Route) System 

Table 3-2 Levels of Significant Exposure to Beryllium - Oral 

LOAEL 

NOEL Less Serious Serious 

(mglkglday) (mglkglday) (mghlday) 

Reference 

Chemical Form 

m 

7J

rn 

5I 

Ic

I 

-

1 

ACUTE EXPOSURE 

Death 

(CBA) (GW) 

INTERMEDIATEEXPOSURE 

Mouse Id 140 (LD50) 

BeS04 

Ashby et al. 1990 

2 

3 

Dog 

(Beagle) 

Systemic 

(SpragueDawley) 

Rat Bd Wt 0.7 

12 (increased mortality) Morgareidge et al. 1976 

BeS04 

Freundt and lbrahim 1990 

BeS04 

0 

4 Rat 

(NS) 

Musdskel 35 (rickets) Guyatt et al. 1933 

BeC03 

i

I 

5 Rat 

(Wistar) 

Musdskel 345 (rickets) Jacobson1933 

BeCO3+Be(OH)2 

Bd Wt 345 

6 Rat 

(NS) 

Musclskel 70 (severe rickets) Kay and Skill 1934 

BeC03 

Metab 70 (decreased blood phosphate 

levels) 

7 Rat 

(Wistar) 

4wk 

(F) 

Bd Wt 480 (18% decrease in body weight 

gain) 

Matsurnoto et al. 1991 

BeC03 

Metab 480 (decreased serum phosphate 

and alkaline phosphatase) 
Table 3-2 Levels of Significant Exposure to Beryllium - Oral (continued) W 

rn 

a 

Exposure/ LOAEL

Duration/

a Serious Reference Key to Species Frequency NOAEL Less Serious 

figure (Strain) (Specific Route) System (mglkglday) (mglkglday) (mghllday) Chemical Form 

CHRONIC EXPOSURE 

Morgareidgeet al. 1975 8 Rat 2 Yr Resp 31 

(Wistar) (F) be504 

Cardio 31 

Gastro 31 

Hemato 31 

Musclskel 31 

w 

Hepatic 31 1 

5

rn 

Renal 31 

1 

rn Endocr 31 -n 

-n 

rn 

Ocular 31 2 

(I) 

Bd Wt 31 

9 Rat 3.2 yr Schroeder and Mitchener 1975a 

Resp 0.7 

(Long- Evans) (W) be504 

Cardio 0.7 

Hepatic 0.7 

Renal 0.7 

Bd Wt 0.7 

Metab 0.7 
Exposure/ 

Duration/ a Key to Species Frequency figure (Strain) (Specific Route) 

CHRONIC EXPOSURE 

10 Mouse 898 d 

(Swiss) (W) 

Reproductive 

12 Dog 143-172 Wk 

(Beagle) (F) 

Table 3-2 Levels of Significant Exposure to Beryllium - Oral (continued) 

LOAEL 

NOAEL Less Serious Serious Reference 

System (mglkglday) (mglkglday) (mglkglday) Chemical Form 

Schroeder and Mitchener 1975b 

Resp 1 BeS04 

Cardio 

Hemato 

Hepatic 

Renal 

Bd Wt 1 

Morgareidge et al. 1976 

Resp 12 M BeS04 

Cardio 12 M 

12 M (ulcerative and inflammatory Gastro Ib lesions in the gastro intestinal 

tract of 9110 dogs) Hemato 1 12 M (erythroid hypoplasia of bone 

marrow) 

Musclskel 12 M 

Hepatic 12 M 

Renal 12 M 

Endocr 12 M 

Dermal 12 M 

Ocular 12 M 

12 M (weight loss and anorexia) Bd Wt 1 

Morgareidge et al. 1976 

I BeS04 

w 

rn

5

I 

m 

n 

n 

rn

2 

(n 

m 

m

7J

5I

1

C

5: 
Table 3-2 Levels of Significant Exposure to Beryllium - Oral (continued) 

Exposure1 LOAEL 

Duration/ 

a NOAEL Less Serious Serious Reference Key to Species Frequency 

figure (Strain) (Specific Route) System (mglkglday) (mglkglday) (mglkglday) Chemical Form 

CHRONIC EXPOSURE 

Developmental 

13 Dog 143-172 wk Morgareidge et al. 1976 

1 

(Beagle) (F) BeS04 

aThe number corresponds to entries in Figure 3-2. 

b Used to derive a chronic-duration oral minimal risk level (MRL) of 0.002 mg Belkglday. The MRL was calculated using a benchmark dose method: the probit model was fit to the 

combined male and female incidence of ulcerative lesions in the small intestine and average doses for male and female dogs to estimate a BMDL (defined as the 95% lower 

confidence limit on the dose corresponding to a 10% increase in the incidence of small intestine lesions compared with controls) of 0.56 mglBelday. The BMDL was divided by an 

uncertainty factor of 100 (10 for extrapolation from animals to humans and 10 for intrahuman variability) and a modifying factor of 3 (to account for the lack of a study which supports u the gastrointestinal effects found in the Morgareidge et al. [I9761 dog study and the uncertainty as to wether the benchmark dose in the NOAEL). I 

m Bd Wt = body weight; Be = Beryllium; BeC12 = beryllium chloride; BeCOB.Be(OH)2 = beryllium carbonate: BeFZ = beryllium fluoride; Be0 = beryllium oxide: BeS04 = beryllium F sulfate: Cardio = cardiovascular; d = day&); Endocr = endocrine; (F) = feed; (G) = gavage; Gastro = gastrointestinal; (GW) = gavage in water; hemato = hematological;hr = hour@); -I

I LD50 = lethal dose, 50% kill: LOAEL = lowest-observed-adverse-effect level: Musclskel = musculoskeletal; NOAEL = no-observed-adverse-effect level; (NS) = not specified; Resp = rn respiratory; (W) = drinking water; wk = week@): yr = year(s) 4 
_____ 

Figure 3-2. Levels of Significant Exposure to Beryllium - Oral 

Acute (114 days) 

mglkglday 

- 1ooa 

w 

I 

5

rn 

I 

rn 

T

n 

rn 

0

I 

cn 

1O( 

c-Cat -Humans f-Ferret n-Mink Cancer Effect Level-Animals Cancer Effect Level-Humans LD50/LC50

k-Monkey j-Pigeon o-Other LOAEL, More Se[ious-Animals A LOAEL, More Serious-Humans : Minimal Risk Level 

m-Mouse e-Gerbil CP LOAEL, Less Serious-Animals A LOAEL, Less Serious-Humans : for effects 

h-Rabbit s-Hamster 0NOAEL -Animals NOAEL- Humans A other than 

a-Sheep g-Guinea Pig Cancer 
1000 

100 

1c 

1 

0.1 

Figure 3-2. Levels of Significant Exposure to Beryllium - Oral (Continued) 

Intermediate (1 5-364 days) 

Systemic 

mglkglday 

e2d 

e5r 

e6r 

e4r 

(D7r 

05r 

a6r 

I-’ 

I 

rn 

5 

I 

rn 

n 

n 

rn 

0 

c-Cat -Humans f-Ferret n-Mink Cancer Effect Level-Animals Cancer Effect Level-Humans LD50/LC50 

d-Dog k-Monkey j-Pigeon o-Other LOAEL, More Serious-Animals A LOAEL, More Serious-Humans : Minimal Risk Level 

r-Rat rn-Mouse e-Gerbil a LOAEL, Less Serious-Animals A LOAEL, Less Serious-Humans : for effects 

p-Pig h-Rabbit s-Hamster 0 NOAEL -Animals A NOAEL - Humans A other than 

q-Cow a-Sheep g-Guinea Pig _____- Cancer 
100 

10 

1 

0.1 

0.01 

~ 0.001 

08r 08r 

- Olld Olld 

- OlOm 

09r 

c-Cat -Humans

d-Dog k-Monkey

r-Rat m-Mouse 

p-Pig h-Rabbit 

q-Cow a-Sheep 

Figure 3-2. Levels of Significant Exposure to Beryllium - Oral (Continued) 

Chronic (2365 days) 

Systemic 

08r 08r 08r 08r 08r 08r 08r O8r 

Olld alld Olld Olld Olld Olld Olld Olld Olld 

Olld010m 

Cancer Effect Level-Animals Cancer Effect Level-Humans 

j-Pigeon o-Other

f-Ferret n-Mink 

LOAEL, More Serious-Animals A LOAEL, More Serious-Humans 

e-Gerbil (3LOAEL, Less Serious-Animals A LOAEL, Less Serious-Humans 

s-Hamster 0NOAEL- Animals A NOAEL - Humans 

g-Guinea Pig 

w 

I 

rn

5

I 

m 

-n 

n 

m

2 cn 

: LD50/LC50 Minimal Risk Level 

: for effects 

other than 

Cancer 
 

 

 

BERYLLIUM 82 

3. HEALTH EFFECTS 

The highest NOAEL values and all reliable LOAEL values for each systemic effect in each species and 

duration category are recorded in Table 3-2 and plotted in Figure 3-2. 

Respiratory Effects. The respiratory system does not appear to be a target of oral exposure to 

beryllium or its compounds. Thickening of the alveolar epithelium with areas of necrosis was observed in 

rats maintained on diets containing beryllium nitrate that provided 2 mg beryllium/kg every 3 days for 

40 days (Goel et al. 1980). However, since the beryllium nitrate was mixed with food pellets, it is 

possible that the lung effects resulted from aspiration of the beryllium nitrate particulates into the lungs 

during feeding. 

No microscopic lung abnormalities were observed in dogs exposed to 12 mg beryllium/kg/day as 

beryllium sulfate in the diet for 143-172 weeks, respectively (Morgareidge et al. 1976) or in rats exposed 

to #31 mg beryllium/kg/day as beryllium sulfate in the diet for 2 years (Morgareidge et al. 1975). 

Furthermore, chronic exposure to 0.7 or 1 mg beryllium/kg/day as beryllium sulfate in the drinking water 

did not cause lung effects in rats and mice (Schroeder and Mitchener 1975a, 1975b). 

Cardiovascular Effects. Data regarding cardiovascular effects in animals after oral exposure to 

beryllium or its compounds are limited. Dietary exposure to beryllium sulfate did not result in 

microscopic abnormalities in the heart or aorta of dogs exposed to 12 mg beryllium/kg/day for 143­

172 weeks (Morgareidge et al. 1976) or rats exposed to #31 mg beryllium/kg/day for 2 years 

(Morgareidge et al. 1975). Histological examination revealed that chronic exposure to 0.7 or 1 mg 

beryllium/kg/day as beryllium sulfate in the drinking water did not cause cardiac effects in rats or mice 

(Schroeder and Mitchener 1975a, 1975b). The results from these studies suggest that oral exposure to 

beryllium is not likely to cause cardiac effects. However, other indices of cardiovascular effects, such as 

blood pressure determinations, were not examined. 

Gastrointestinal Effects. In a chronic exposure study, extensive ulcerative and inflammatory 

lesions were observed in the small intestine, stomach, and large intestine of dogs exposed to 12 mg 

beryllium/kg/day as beryllium sulfate in the diet; similar, but less severe, lesions were observed in 1 of 

10 dogs exposed to 1 mg beryllium/kg/day (Morgareidge et al. 1976). No lesions were observed in dogs 

exposed to 0.1 mg beryllium/kg/day. The dose-response data from this study were used to derive a 

chronic-duration MRL of 0.002 mg beryllium/kg/day. The only other study that examined gastrointestinal 

tract tissues was a chronic rat study conducted by the same group. No microscopic abnormalities of the 
 

 

 

BERYLLIUM 83 

3. HEALTH EFFECTS 

stomach, small intestine, or large intestine were observed in rats exposed to #31 mg beryllium/kg/day as 

beryllium sulfate in the diet for 2 years (Morgareidge et al. 1975). 

Hematological Effects. Two studies examined hematological end points in animals after oral 

exposure to beryllium sulfate. Erythroid hypoplasia of the bone marrow and slight decreases in 

erythrocyte, hemoglobin, and hematocrit levels were observed in dogs exposed to 12 mg 

beryllium/kg/day; no effects were observed at 1 mg beryllium/kg/day (Morgareidge et al. 1976). It is 

likely that these effects were secondary to the severe gastrointestinal hemorrhages also observed in these 

animals rather than a direct effect on the hematological system. No evidence of microscopic 

abnormalities of the bone marrow or spleen was observed in rats exposed to #31 mg beryllium/kg/day for 

2 years (Morgareidge et al. 1975). 

Musculoskeletal Effects. Early studies indicate that rats fed large amounts of beryllium carbonate 

in the diet developed rickets. Rickets were observed in rats fed diets supplemented with 35–840 mg 

beryllium/kg/day as beryllium carbonate (Guyatt et al. 1933; Jacobson 1933; Kay and Skill 1934). The 

severity in the fragility of the bones increased with increasing concentrations of beryllium. These 

“beryllium rickets” are likely due to impaired gastrointestinal phosphate absorption rather than a direct 

effect of beryllium on bone. Following ingestion of beryllium carbonate, the beryllium in the gut binds to 

soluble phosphorus compounds and forms an insoluble beryllium phosphate; the rickets are a result of the 

decreased phosphorus levels. Although there are a number of methodological deficiencies in these 

studies, such as small numbers of animals per group and lack of statistical analysis, collectively, the 

studies suggest a relationship between beryllium carbonate ingestion and the occurrence of rickets. No 

bone effects were observed in dogs chronically exposed to 12 mg beryllium/kg/day as beryllium sulfate in 

the diet (Morgareidge et al. 1976). Chronic exposure to #31 or #12 mg beryllium/kg/day as beryllium 

sulfate did not cause morphological abnormalities in the muscle tissue of rats (Morgareidge et al. 1975) or 

dogs (Morgareidge et al. 1976), respectively. 

Hepatic Effects. Oral exposure to beryllium compounds causes few effects, if any, on the liver of 

animals. Biochemical analysis of the lipid and protein contents of liver homogenates from rats exposed to 

0.2 mg beryllium/kg/day as beryllium sulfate did not reveal any hepatic damage (Reeves 1965), however, 

histological examination was not performed. 

Dogs fed 12 mg beryllium/kg/day as beryllium sulfate for 143-172 weeks (Morgareidge et al. 1976) and 

rats fed #31 mg beryllium/kg/day as beryllium sulfate for 2 years (Morgareidge et al. 1975) did not 
 

 

 

 

BERYLLIUM 84 

3. HEALTH EFFECTS 

develop morphological abnormalities of the liver or changes in liver weight. Rats given 0.7 mg 

beryllium/kg/day as beryllium sulfate in drinking water for 3.2 years had transient increases in serum 

cholesterol (Schroeder and Mitchener 1975a). Histological examination of the livers of the exposed rats 

did not provide evidence of morphological alterations. In mice exposed to beryllium sulfate via a similar 

regimen, no changes in serum cholesterol or morphological abnormalities were observed (Schroeder and 

Mitchener 1975b). 

Renal Effects. Oral exposure to beryllium compounds causes few renal effects, if any, in animals. 

Histological examination of rats fed #31 mg beryllium/kg/day as beryllium sulfate for 2 years established 

no evidence of morphological damage to kidney tissue; however, kidney weight increased slightly 

(Morgareidge et al. 1975). No significant alterations in kidney weight or histological examinations were 

observed in dogs exposed to 12 mg beryllium/kg/day as beryllium sulfate in the diet for 143- 172 weeks 

(Morgareidge et al. 1976). Morphological alterations of the kidney were not observed in either sex of rats 

or mice exposed to 0.6–1 mg beryllium/kg/day as beryllium sulfate, respectively (Schroeder and 

Mitchener 1975a, 1975b). Female rats, however, developed a transient glucosuria (Schroeder and 

Mitchener 1975a). 

Endocrine Effects. There is limited information on potential endocrine effects following oral 

exposure to beryllium. No adverse effects were observed in the adrenal, thyroid, pituitary, or pancreas of 

dogs exposed to 12 mg beryllium/kg/day as beryllium sulfate in the diet for 143-172 weeks (Morgareidge 

et al. 1976) or in rats exposed to #31 mg beryllium/kg/day as beryllium sulfate in the diet for 2 years 

(Morgareidge et al. 1975). 

Dermal Effects. Information regarding dermal effects in animals after oral exposure to beryllium or 

compounds is limited. Histological examination of the skin of rats exposed to #31 mg beryllium/kg/day 

as beryllium sulfate in the diet for 2 years (Morgareidge et al. 1975) or in dogs exposed to 12 mg 

beryllium/kg/day as beryllium sulfate in the diet for 143-172 weeks (Morgareidge et al. 1976) did not 

indicate morphological changes. 

Ocular Effects. Two studies examined the eyes of animals repeatedly exposed to beryllium sulfate in 

the diet. No ocular effects were observed in rats exposed to #31 mg beryllium/kg/day for 2 years 

(Morgareidge et al. 1975) or dogs exposed to 12 mg beryllium/kg/day for 143-172 weeks (Morgareidge et 

al. 1976). 
 

 

BERYLLIUM 85 

3. HEALTH EFFECTS 

Body Weight Effects. In general, exposure to beryllium sulfate in the diet or drinking water does not 

adversely affect body weight gain. Intermediate-duration exposure to high doses of beryllium carbonate 

in the diet (480 mg beryllium/kg/day) resulted in an 18% decrease in body weight gain in rats 

(Matsumoto et al. 1991). At lower doses (0.7 mg beryllium/kg/day), no body weight effects were 

observed (Freundt and Ibrahim 1990). Anorexia and weight loss was observed in dogs exposed to 12 mg 

beryllium/kg/day as beryllium sulfate in the diet; no effects on body weight gain were observed in dogs 

exposed to #1 mg beryllium/kg/day (Morgareidge et al. 1976). The weight loss observed at the highest 

dose was probably secondary to the ulcerative gastrointestinal lesions present in these animals. No 

alterations in weight gain were observed in rats (Morgareidge et al. 1975) chronically exposed via the diet 

to 31 mg beryllium/kg/day, or in rats (Schroeder and Mitchener 1975a) and mice (Schroeder and 

Mitchener 1975b) exposed via drinking water to 0.7 or 1 mg beryllium/kg/day, respectively. 

Metabolic Effects. There are very limited data on metabolic effects in animals following oral 

exposure to beryllium or its compounds. Decreases in serum phosphate levels and alkaline phosphatase 

activity were observed in rats exposed to $70 mg beryllium/kg/day as beryllium carbonate in the diet 

(Kay and Skill 1934; Matsumoto et al. 1991). As discussed under Musculoskeletal Effects, it is likely 

that these effects are due to beryllium binding to soluble phosphorus compounds causing a decrease in 

phosphorus absorption. 

3.2.2.3 Immunological and Lymphoreticular Effects 

No studies were located regarding immunological effects in humans after oral exposure to beryllium or its 

compounds. 

No histopathological lesions were observed in the spleen, lymph nodes, or thymus of rats chronically 

exposed to #31 mg beryllium/kg/day as beryllium sulfate in the diet (Morgareidge et al. 1975) or in dogs 

exposed to 12 mg beryllium/kg/day as beryllium sulfate in the diet for 143-172 weeks (Morgareidge et al. 

1976). More sensitive tests of the immune function were not conducted. 
BERYLLIUM 86 

3. HEALTH EFFECTS 

3.2.2.4 Neurological Effects 

No studies were located regarding neurological effects in humans after oral exposure to beryllium or its 

compounds. 

No changes in brain weight and no histopathological lesions were observed in the brain, nerve, or spinal 

cord of rats chronically exposed to #31 mg beryllium/kg/day as beryllium sulfate in the diet (Morgareidge 

et al. 1975) or in dogs exposed to 12 mg beryllium/kg/day as beryllium sulfate in the diet for 143­

172 weeks (Morgareidge et al. 1976). This information is insufficient to conclude that beryllium does not 

cause neurological effects because more sensitive neurological or neurobehavioral tests were not 

performed. 

3.2.2.5 Reproductive Effects 

No studies were located regarding reproductive effects in humans after oral exposure to beryllium or its 

compounds. 

There is limited information available on beryllium effect on reproduction. In a chronic duration dog 

study conducted by Morgareidge et al. (1976), male and female dogs were housed together at the time of 

the second heat, were allowed to mate and wean their pups; the study authors reported that there were no 

significant alterations in the number of pregnancies, number of pups, or number of live pups observed at 

doses of #1 mg beryllium/kg/day as beryllium sulfate in the diet. The result of this study should be 

interpreted with caution because very few study details were provided. Rats maintained for 2 years on 

diets containing beryllium sulfate had a significantly decreased average testes-to-body weight ratio at 

concentrations of 0.3 and 2.8 mg beryllium/kg/day, but not at #31 mg beryllium/kg/day (Morgareidge et 

al. 1975). Histological examination of the testes, prostate, seminal vesicles, and epididymis did not reveal 

any abnormalities. No decrease in ovary weight was observed in female rats similarly exposed. 

Furthermore, histological examination of the ovaries, uterus, and oviducts did not reveal any 

abnormalities (Morgareidge et al. 1975). The absence of further evidence of adverse effects of 

reproductive organs and of a positive dose relationship makes the toxicological significance of the 

decreased testes-to-body weight ratio unclear. 
BERYLLIUM 87 

3. HEALTH EFFECTS 

3.2.2.6 Developmental Effects 

No studies were located regarding developmental effects in humans after oral exposure to beryllium or its 

compounds. 

There is limited information on beryllium’s potential to induce developmental effects in animals 

following oral exposure. As discussed under Reproductive Effects, the Morgareidge et al. (1976) chronic 

dog study co-housed males and females, allowed them to mate, and wean their pups. Pups in the first 

litter were examined for gross and skeletal malformations. No significant alterations in the occurrence of 

gross or skeletal malformations, number of live pups, pup body weights, or pup survival were observed at 

1 mg beryllium/kg/day; however, stillborn or cannibalized pups dying within the first few postnatal days 

were not examined. 

3.2.2.7 Cancer 

No studies were located regarding cancer in humans after oral exposure to beryllium or its compounds. 

Beryllium has not been found to cause cancer in animals after oral exposure. This could be due to the 

poor absorption of beryllium compounds from the gastrointestinal tract. Nonsignificant increases in the 

number of lung reticulum cell carcinomas were observed in male rats exposed to 0.3 or 2.8 mg 

beryllium/kg/day as beryllium sulfate in the diet for 2 years; the incidences were 10/50, 17/50, 16/50, and 

5/50 in males and 5/50, 7/50, 7/50, and 5/50 in females in the 0, 0.3, 2.8, and 31 mg beryllium/kg/day 

groups, respectively (Morgareidge et al. 1975). No differences in the number of reticulum cell carcinoma 

bearing rats were observed in the beryllium-exposed rats (18/50, 16/50, and 13/50 for males and 11/50, 

7/50, and 8/50 for females in the 0.3, 2.8, and 31 mg beryllium/kg/day groups, respectively) compared to 

controls (12/50 and 8/50 for males and females, respectively). The incidence of tumors in rats or mice 

exposed chronically to 1 mg beryllium/kg/day as beryllium sulfate in the drinking water was not 

significantly altered, although the incidence of total tumors in treated male rats (9/33) was slightly 

increased, compared to controls (4/26) (Schroeder and Mitchener 1975a, 1975b). The incidence of 

neoplasms was not significantly increased in dogs exposed to 12 or 1 mg beryllium/kg/day as beryllium 

sulfate in the diet for 33 or 172 weeks, respectively (Morgareidge et al. 1976). 
 

BERYLLIUM 88 

3. HEALTH EFFECTS 

3.2.3 Dermal Exposure 

3.2.3.1 Death 

No studies were located regarding death in humans or animals after dermal exposure to beryllium or its 

compounds. 

3.2.3.2 Systemic Effects 

No studies were located regarding cardiovascular, gastrointestinal, musculoskeletal, hepatic, renal, 

endocrine, ocular, or body weight effects in humans or animals after dermal exposure to beryllium or its 

compounds. 

Most of the available information on the systemic toxicity of beryllium following dermal exposure comes 

from a series of studies conducted by Marx and Burrell (1973). In these studies, guinea pigs were 

sensitized via 12 biweekly intradermal injections of beryllium sulfate and/or received a single intradermal 

injection of beryllium oxide or a single intradermal injection of beryllium oxide, beryllium sulfate, and 

beryllium fluoride. Another group of guinea pigs received two intraperitoneal injections of beryllium 

sulfate. The study authors note “a number of guinea pigs which were being sacrificed were examined for 

evidence of any systemic involvement of the disease state.” No additional information was provided as to 

which group(s) of animals were examined; however, an assumption can be made that it was animals 

receiving intradermal doses. The observed effects are described below, but are not presented in the LSE 

table or figure. 

Respiratory Effects. No studies were located regarding respiratory effects in humans after dermal 

exposure to beryllium or its compounds. 

Several respiratory effects were described in the Marx and Burrell (1973) study; the observed effects 

included mild to moderate interstitial fibrosis of the alveolar wall, mild to moderate emphysema with 

dilatation of the respiratory bronchioles, hypertrophy of smooth muscle, and mucosal hypertrophy of the 

terminal bronchioles. 
 

 

BERYLLIUM 89 

3. HEALTH EFFECTS 

Hematological Effects. No studies were located regarding hematological effects in humans after 

dermal exposure to beryllium or its compounds. 

Splenic effects were observed in the guinea pigs examined by Marx and Burrell (1973). The observed 

effects in the spleen included follicular hyperplasia and focal hematopoietic tissue hyperplasia and large 

deposits of hemosiderin in the medullary area. 

Dermal Effects. Dermatological abnormalities due to beryllium exposure were reported in the case 

histories of 42 workers exposed to beryllium sulfate, beryllium fluoride, or beryllium oxyfluoride 

(VanOrdstrand et al. 1945). The dermatological manifestations were characterized as edematous, 

papulovesicular dermatitis. Ulceration occurred only after the skin was accidentally abraded. These 

ulcers began as small indurated papules surrounded by an area of erythema which later underwent 

necrosis. Conjunctivitis occurred only as a splash burn or in association with contact dermatitis of the 

face. Granuloma formation was reported in the case histories of 26 beryllium workers with skin lesions 

resulting from cuts and abrasions sustained at work (Williams et al. 1987). Skin biopsies of six workers 

showed that the granulomatous lesions of the skin contained beryllium. Eight other workers had skin 

lesions only. Twelve of the workers had nonspecific inflammation of the skin without granuloma 

(Williams et al. 1987). An allergic contact dermatitis can occur and is most frequently caused by 

beryllium fluoride (Curtis 1951) (see Section 3.2.3.3). 

Delayed hypersensitivity reactions, as described under Immunological and Lymphoreticular Effects, were 

observed in beryllium-sensitized guinea pigs dermally exposed to beryllium sulfate, beryllium fluoride, 

beryllium oxide, or beryllium chloride (Belman 1969; Marx and Burrell 1973). 

3.2.3.3 Immunological and Lymphoreticular Effects 

Thirteen patients with dermatitis as a result of occupational dermal contact with beryllium fluoride, 

ground metallic beryllium, or water drippings from overhead pipes coated with dust of various 

compounds were evaluated with patch tests using different beryllium compounds to determine whether 

the dermatitis was due to an immune response (Curtis 1951). Positive patch tests were obtained in 5 of 

13 patients challenged with 0.019 mg beryllium/mL as beryllium fluoride. The incidence and severity of 

positive reactions increased with increasing concentrations of test substance. The relative ability of the 

compounds to elicit reactions was as follows: beryllium fluoride > beryllium sulfate=beryllium chloride 

> beryllium nitrate. 
BERYLLIUM 90 

3. HEALTH EFFECTS 

Sensitization of guinea pigs with 12 biweekly intradermal injections of 0.0019 or 0.0005 mg beryllium as 

either beryllium fluoride or beryllium sulfate increased the amount of macrophage inhibition factor and 

lymphotoxin when the lymphocytes were cultured with beryllium salts (Marx and Burrell 1973). The 

sensitivity of the lymphocytes to beryllium salts, as noted by the increase in lymphokine levels, could be 

passively transferred from a sensitized donor to a naive recipient. Delayed hypersensitivity reactions also 

developed in guinea pigs tested with beryllium fluoride or beryllium chloride after dermal or 

intracutaneous sensitization with beryllium fluoride (Belman 1969) and in guinea pigs tested with 

beryllium sulfate or metallic beryllium after intradermal sensitization with beryllium sulfate (Zissu et al. 

1996). The LOAEL values for immunological effects in each species and duration category are recorded 

in Table 3-3. 

No studies were located regarding the following health effects in humans or animals after dermal 

exposure to beryllium or its compounds: 

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 

Animal models of chronic beryllium disease have increased our understanding about the potential 

pathogenesis of chronic beryllium disease in humans. Hartley guinea pigs that were injected 

intratracheally with 16 mg beryllium/kg as beryllium oxide calcined at 560 EC developed slight edema 

and had focal interstitial lymphomononuclear infiltration at 1 week after injection (Barna et al. 1981). 

Granulomatous lesions were found at 2 weeks after injection and became progressively more severe at 

4–6 weeks, with the level of severity persisting up to the end of the observation period (6 months). In 

vitro blood lymphocyte transformation tests in response to beryllium sulfate challenge were consistently 

positive with cells from beryllium oxide injected guinea pigs and consistently negative in cells from 

controls. Treatment of the guinea pigs with immunosuppressive agents (prednisone, L-asparaginase, 
C 

Table 3-3 Levels of Significant Exposure to Beryllium - Dermal W 

rn 

;o 

$ Exposure/ r 

Duration/ LOAEL Reference s Species Frequency Chemical Form 

(Strain) (Specific Route) System NOEL Less Serious Serious 

ACUTE EXPOSURE 

lmmunol Lymphoret 

Human Curtis 1951 48 hr 0.19 (allergic dermatitis) mglmi BeS04 

Curtis 1951 

(allergic dermatitis) 

Human 48 hr 0.19 

rnglml BeC12 

Human Curtis 1951 48 hr 0.019 (allergic dermatitis) mglml w 

BeF2 I 

rn

F Curtis 1951 i 

(allergic dermatitis) 

Human 48 hr 0.19 I 

mglml Be( N03)2 

Gn Pig Belman 1969 Ix 0.1 (delayed type (albino) M hypersensitive reaction) BeCI2 

Gn Pig Belman 1969 Ix 0.02 (delayed type (albino) M hypersensitive reaction) BeF2 

Gn Pig Man: and Burrell 1973 Id 0.25 (delayed hypersensitive (Hartley) ug reaction, splenic BeS04 

hyperplasia. lung 

inflammation) 

Zissu et al. 1996 

(delayed type 

Gn Pig 24 hr 3 

~ (Dunkin Hartley) Percent(“’1 hypersensitivity) beryllium sulfate 
Table 3-3 Levels of Significant Exposure to Beryllium - Dermal (continued) m 

rn 

;o

< Exposure1 

Duration1 

Soecies Frequency 

(&rain) (Specific Route) 

INTERMEDIATE EXPOSURE 

lmmunol Lyrnphoret 

Gn Pig 24 wk Ixf2wk 

(Hartley) 

System NOAEL 

LOAEL 

Less Serious 

0'0005 (increased macrophage 

ug inhibition factor and 

T-cell activity) 

Serious 

Reference 

Chemical Form 

Marx and Burrell 1973 

BeS04 

C

K 

BeC12 = beryllium chloride; BeF2 = beryllium fluoride; Be(N03)3 = beryllium nitrate; BeS04 = beryllium sulfate: Gn pig = guinea pig; hr = hour(s); LOAEL = lowest-observed-adverse-effect level; NOAEL = no-observed-adverse-effect level; wk = week(s); x = times 

w 

rn

F 
BERYLLIUM 93 

3. HEALTH EFFECTS 

cytoxan) decreased the severity of beryllium oxide-induced lung disease. Pretreatment with beryllium 

sulfate prior to beryllium instillation delayed the development and reduced the severity of lung granuloma 

and also suppressed the delayed skin reactions to beryllium sulfate injected intradermally in guinea pigs 

intratracheally exposed to beryllium oxide. These experiments demonstrate that the development of 

granulomas in response to beryllium involves cell-mediated immune mechanisms. Similar studies with 

strain 2 and strain 13 guinea pigs demonstrated that strain 2 guinea pigs consistently developed chronic 

beryllium disease, while strain 13 guinea pigs did not, indicating that the immune mechanisms are 

genetically controlled in guinea pigs, and may explain the low prevalence of chronic beryllium disease in 

humans (Barna et al. 1981, 1984). In an attempt to develop a murine model for chronic beryllium disease, 

A/J (H-2a

 haplotype) mice received intratracheal injections of beryllium sulfate or beryllium oxide 

calcined at 550 or 1,100 EC (Huang et al. 1992). In mice that received beryllium oxide, no histological 

differences or differences in bronchoalveolar lavage cells were found from the control mice until 

8 months after instillation. At 8 months, there were moderate infiltrates and diverse microgranulomatous 

lesions, but these were apparently resolved at 10 months. The mice that received beryllium sulfate 

intratracheally were preimmunized with beryllium sulfate subcutaneously. Nonspecific inflammatory 

cells plus perivascular areas of lymphocytic infiltrates were seen at 2 weeks after beryllium sulfate 

instillation; numerous active areas containing macrophages, microgranulomas, and fibrosis were seen at 

4 weeks; more severe granulomas and fibrosis were seen at 8 weeks, but at 20 weeks the lungs were 

generally normal. Results of tests on cells obtained by bronchoalveolar lavage showed increases in 

lymphocytes that corresponded with the time course of pathological changes. At 2 weeks, .30% of the 

lymphocytes expressed the γ/σ T lymphocyte receptor. Most of the lymphocytes at 4 weeks were Thy1+, 

LdT4+ (CD4+), and expressed the α/β T lymphocyte receptor. Significant in vitro proliferation of 

bronchoalveolar lavage lymphocytes from preimmunized mice in response to beryllium sulfate was 

observed. During the acute phase (2 weeks), macrophage activation antigens were expressed, while at 

later times beyond the acute inflammatory phase, monocyte-macrophage antigens were expressed. 

Similar effects could not be induced in BALB/c (H-2d haplotype) or C57BL/6 (H-2b haplotype) mice, 

suggesting that genetic differences at the H-2 major histocompatibility complex gene complex may 

account for the differential responses to beryllium sulfate. Another cellular mechanism by which 

beryllium is thought to induce toxicity is by interaction with the cell lysosome (Witschi and Aldridge 

1968). It has been postulated that beryllium destroys the integrity of the lysosomal membrane and 

releases lysosomal enzymes, which are injurious to the cell (Reeves and Preuss 1985). 
 

BERYLLIUM 94 

3. HEALTH EFFECTS 

3.3 GENOTOXICITY 

Genotoxic Effects. No studies were located regarding genotoxicity in humans after inhalation, oral, 

or dermal exposure to beryllium or its compounds. CBA mice were exposed by gavage to 117 and 

71 mg/kg as beryllium sulfate corresponding to 80 and 50% of the LD50 values, respectively (Ashby et al. 

1990). The number of micronucleated polychromatic erythrocytes was not exceptional 24, 48, and 

72 hours after dosing. In vitro studies are summarized in Table 3-4. The results of genotoxicity assays of 

soluble beryllium compounds are inconsistent; however, the carcinogenicity of beryllium is supported by 

the positive mutagenic potential reported in some of these studies. The inconsistencies may have been 

due to the physical/chemical properties of beryllium; in particular the binding of beryllium to phosphate, 

hydroxide, or proteins in the culture media. Beryllium nitrate was not mutagenic in the Salmonella 

typhimurium reverse mutation assay (Ames test) (Arlauskas et al. 1985). Beryllium sulfate was 

mutagenic in the forward mutation assay in Bacillus subtilis (Kanematsu et al. 1980) but was not 

mutagenic in the Ames test, regardless of the presence of microsomal fractions (Ashby et al. 1990; 

Rosenkranz and Poirier 1979; Simmon 1979b). Beryllium chloride was mutagenic in the reverse 

mutation assay in Photobacterium fischeri (Ulitzur and Barak 1988). Beryllium chloride was not 

mutagenic in the forward mutation assay with Escherichia coli (Zakour and Glickman 1984). Beryllium 

sulfate did not cause gene mutations in Saccharomyces cerevisiae (Simmon 1979b). Gene mutations 

were induced in whole mammalian cell cultures by the addition of either beryllium sulfate or beryllium 

chloride (Hsie et al. 1979; Miyaki et al. 1979). According to one study, beryllium sulfate induced 

chromosomal aberrations in mammalian cells (Larramendy et al. 1981); however, other studies indicate 

that beryllium sulfate did not induce chromosomal aberrations in cultured mammalian cells (Ashby et al. 

1990; Brooks et al. 1989). Beryllium sulfate did not affect deoxyribonucleic acid (DNA)-repair in 

mammalian cells (Williams et al. 1989). Differences in the positive and negative results depend on the 

assay conditions, the concentrations of the beryllium compounds in vitro, and the differences among 

bacterial strains. Thus, soluble beryllium compounds appear to be weakly genotoxic. 
Table 3-4. Genotoxicity of Beryllium and Its Compounds In Vitro 

With Without 

Species (test system) End point activation activation Reference 

Prokaryotic organisms: 

Salmonella typhimurium Gene mutation — — Arlaukas et al. 1985; Ashby et 

al. 1990; Rosenkranz and Poir1979; Simmon et al. 1979; Simmon 1979a 

S. typhimurium Gene mutation No data — Arlauskas et al. 1985 Bacillus subtilis Gene mutation No data + Kanematsu et al. 1980 

Escherichia coli Gene mutation No data — Zakour and Glickman 1984 

Photobacterium fischeri Gene mutation No data + Ulitzur and Barak 1988 

Eukaryotic organisms: 

Fungi: 

Saccharomyces cerevisiae Gene mutation No data — Simmon 1979b 

Mammalian cells: 

Chinese hamster ovary K1­ Gene mutation No data + Hsie et al. 1979 

BH4 cell Chinese hamster ovary cell Chromosomal aberration No data — Brooks et al. 1989 

Chinese hamster CHL cells Chromosomal aberration — — Ashby et al. 1990 

Chinese hamster V79 cells Gene mutation No data + Miyaki et al. 1981 

Human lymphocytes Chromosomal aberration No data + Larramendy et al. 1981 

Rat hepatocytes DNA-repair No data — Williams et al. 1989 

Syrian hamster cells Chromosomal aberration No data + Larramendy et al. 1981 

— = negative result; + = positive result; CHL = Chinese hamster lungs; DNA = deoxyribonucleic acid 
BERYLLIUM 96 

3. HEALTH EFFECTS 

3.4 TOXICOKINETICS 

3.4.1 Absorption 

3.4.1.1 Inhalation Exposure 

Beryllium compounds are absorbed primarily through the lungs, but sufficient information to determine 

the rate and extent of absorption was not located. Due to an accidental leakage of beryllium dust in a 

laboratory, 25 people were exposed to an undetermined concentration for 10–20 hours (Zorn et al. 1986). 

The day after exposure, serum beryllium levels were 3.5±0.47 ppb beryllium, compared to 1.0 ppb in 

unexposed controls. Six days later, the serum level decreased to 2.4±0.3 ppb beryllium, and 2–8 weeks 

after exposure the serum levels returned to normal. The biological half-time of beryllium was calculated 

to be 2–8 weeks. In eight men accidently exposed to .8 ng beryllium/m3

 as beryllium chloride for 

4–6 hours/day for 10 days, the beryllium levels in urine and blood increased 4-fold above the levels of 

.1 ng beryllium/g of either blood or urine in unexposed individuals (Stiefel et al. 1980). 

Rats exposed to 0.034 mg beryllium/m3

 as an aerosol of beryllium sulfate 7 hours/day, 5 days/week for 

72 weeks achieved steady state concentrations in the lungs in .36 weeks of exposure (Reeves and 

Vorwald 1967). The beryllium concentration in tracheobronchial lymph nodes peaked between 36 and 

52 weeks, and decreased thereafter. In guinea pigs and rats exposed to 2–40 mg beryllium/m3

 as 

beryllium nitrate for 16 hours, steady-state concentrations in the blood were reached after 8–12 hours of 

exposure (Stiefel et al. 1980). 

3.4.1.2 Oral Exposure 

No studies were located regarding absorption in humans after oral exposure to beryllium or its 

compounds. 

Beryllium and its compounds are poorly absorbed from the gastrointestinal tract in animals. Urinary 

excretion data from rats treated by gavage with radioactive beryllium chloride indicate that the cumulative 

excretion of beryllium in the urine and feces was 0.11 and 104.7% of the total dose, respectively 

(Furchner et al. 1973). In mice, dogs, and monkeys similarly exposed, the urinary output was 0.24, 0.38, 

and 3.71% of the total dose, respectively, while most of the radiolabel was excreted in the feces. 

Therefore, although intestinal absorption of beryllium varies somewhat among species, beryllium was 
BERYLLIUM 97 

3. HEALTH EFFECTS 

poorly absorbed in these animals. Mice exposed to radioactive beryllium retained beryllium in the 

gastrointestinal tract (LeFevre and Joel 1986). The amount found in the tissues other than intestinal was 

<0.1%. 

Urinary excretion accounted for #0.5% of the total dose of beryllium sulfate administered to rats as 

0.019 and 0.190 mg beryllium/kg/day in drinking water for 24 weeks (Reeves 1965). The percent 

absorption, determined as the percentage of the dose that could be recovered from the total body load and 

excreta, was #0.9% in the 0.019 mg beryllium/kg/day group and #0.2% in the 0.190 mg beryllium/kg/day 

group. Rats exposed to #31 mg beryllium/kg/day as beryllium sulfate in drinking water for 2 years 

excreted very little beryllium via the urine (Morgareidge et al. 1975). Oral absorption of beryllium and its 

compounds may be reduced by the formation of beryllium phosphate precipitates in the alkaline 

environment of the intestine (Reeves 1965). 

3.4.1.3 Dermal Exposure 

It is unlikely that beryllium is absorbed through intact skin. Skin ulceration in workers exposed to 

beryllium occurred only after the skin was accidentally cut or abraded (Williams et al. 1987). 

Only small amounts of beryllium were absorbed through the tail skin of rats after exposure to an aqueous 

solution of beryllium chloride (Petzow and Zorn 1974). Beryllium has been demonstrated to bind to 

alkaline phosphatase and nucleic acids in guinea pig epidermis in vitro (Belman 1969). This binding 

could account for the inefficient transfer of beryllium from the epidemis to the blood. 

3.4.2 Distribution 

Average concentrations of beryllium were measured in human organs as follows: 0.21 ppm in lungs; 

0.08 ppm in brain; 0.07 ppm in both the kidney and spleen; 0.04 ppm in each of liver, muscle, and 

vertebrae; 0.03 ppm in heart; and 0.02 in bone (Meehan and Smythe 1967). Further information 

regarding the nature of exposure (e.g., environmental or occupational) or the source of the organ samples 

(e.g., autopsy or biopsy) was not provided. A study by Krachler et al. (1999a) provides evidence that 

beryllium is transferred across the placenta and excreted via breast milk. The levels of beryllium in 

umblical cord serum and in colostrum were higher than in maternal serum. 
BERYLLIUM 98 

3. HEALTH EFFECTS 

3.4.2.1 Inhalation Exposure 

In eight men exposed to .8 ng beryllium/m3

, 4–6 hours/day for 10 days due to an accidental leak of 

beryllium chloride, 60–70% of the beryllium found in the blood was bound to two classes of serum 

proteins, prealbumins and γ-globulins (Stiefel et al. 1980). 

Beryllium is widely distributed to the organs of animals, as a result of pulmonary absorption. 

Immediately after rats were exposed to radioactive beryllium (beryllium sulfate and beryllium chloride) 

for 3 hours, the percentage of total body radioactivity in tissues was 60% in lungs, 0.9% in the liver, 1.5% 

in the kidney, 0.1% in the spleen, 0.4% in the heart, 1.4% in the brain, 9.5% in the muscle, 13.5% in the 

skeleton, 5.0% in the blood, and 10% in the excreta (Zorn et al. 1977). After 408 hours, the liver, spleen, 

heart, brain, and muscle had concentrations <0.0005%; concentrations in the kidneys, skeleton, blood, 

and excreta were 0.0005, 6.8, 0.05, and 92.0%, respectively. The beryllium concentrations in the bone 

increased until 96 hours after exposure and then decreased. Dogs exposed to beryllium oxide calcined at 

500EC had higher beryllium concentrations in the extrapulmonary tissue, principally the liver and 

skeleton, than dogs exposed to beryllium oxide calcined at 1,000 EC, due to the greater solubility of the 

500 EC calcined product (Finch et al. 1990). The translocation of beryllium to the tracheobronchial 

lymph nodes increased and by day 64 accounted for a higher concentration than found in the lung. 

Beryllium was also detected in the liver, skeleton, and blood. 

Distribution studies in rats and guinea pigs exposed to 2–40 mg beryllium/m3

 as beryllium nitrate for 

16 hours report that 60–70% of the beryllium in the blood was bound to prealbumins and γ-globulins 

(Stiefel et al. 1980). Rats and hamsters exposed to beryllium oxide did not have detectable beryllium 

concentrations in the liver, skeleton, or urine 7 days after exposure (Rhoads and Sanders 1985; Sanders et 

al. 1975). At 63 days after exposure, 1.7% of the initial alveolar deposit was present in the pulmonary 

lymph nodes in rats. Exposure to 0.04 mg beryllium/m3

 as beryllium sulfate for 90–100 days resulted in 

the following concentrations (in μg beryllium/g fresh tissue) of beryllium in rabbits: 1.6 in the lungs, 

0.02 in the femur, 0.01 in the spleen, 0.004 in the liver, and 0.003 in the kidney (Stokinger et al. 1950). 

Dogs similarly exposed had the highest concentrations in the pulmonary lymph node (0.7), followed by 

lung (0.6), femur (0.03), spleen (0.01), liver (0.01), and kidney (0.003). In monkeys, the pulmonary 

lymph nodes (1.3) also had the highest concentrations followed by lung (1.2), spleen (0.5), femur (0.1), 

and kidney (0.01). In cats, the concentrations of beryllium from greatest to least were lung (0.08), femur 

(0.03), liver (0.02), spleen (0.01), and kidney (0.01). In rats, hamsters, and monkeys exposed to 0.21 or 

0.62 mg beryllium/m3

 as bertrandite or beryl ore, concentrations were highest in the lung followed by 
BERYLLIUM 99 

3. HEALTH EFFECTS 

bone or liver, and kidney (Wagner et al. 1969). The greater degree of distribution of beryllium sulfate, 

compared with beryllium oxide or the ores, reflects its greater solubility and absorption rate. 

3.4.2.2 Oral Exposure 

No studies were located regarding distribution in humans after oral exposure of beryllium or its 

compounds. 

Beryllium is poorly absorbed from the gastrointestinal tract in animals; however, that which is absorbed is 

distributed to the organs and tissues. Beryllium was found in the liver, large intestine, small intestine, 

kidneys, lungs, stomach, and spleen in hamsters given beryllium sulfate, beryllium oxide, or beryllium 

metal in the diet for 3–12 months (Watanabe et al. 1985). In mice given a radioactive dose of beryllium 

chloride by gavage, the accumulation of radioactivity was greatest in the liver followed by the kidney, 

mesenteric lymph nodes, lungs, blood, and carcass, 3 hours after exposure (LeFevre and Joel 1986). The 

pattern of beryllium distribution to tissues and organs in rats given beryllium sulfate indicated that as the 

exposure duration increases, accumulation levels also increase (Reeves 1965). In tissue, beryllium 

concentrations were highest in the gastrointestinal tract (with contents), followed by bone, blood, and 

liver. Other studies indicate that in animals, high levels of beryllium accumulate in bone tissue as a result 

of oral exposure to the chemical or its compounds. In rats treated by gavage with radioactive beryllium 

chloride, the greatest accumulation (other than that in the gastrointestinal tract) was detected in the bone, 

followed by viscera, pelt, and muscle (Furchner et al. 1973). Beryllium accumulation in the bones of rats 

exposed for 2 years to dietary concentrations of the chemical was proportional to the administered dose 

(Morgareidge et al. 1975). 

3.4.2.3 Dermal Exposure 

No studies were located regarding distribution in humans or animals after dermal exposure to beryllium 

or its compounds. The lack of data is expected because beryllium is poorly absorbed after dermal 

exposure (see Section 3.4.1.3). 

3.4.2.4 Other Routes of Exposure 

In rats receiving a single intravenous injection of radiolabelled beryllium sulfate, circulating beryllium 

was found almost exclusively in the plasma (Vacher and Stoner 1968). Two fractions of plasma 
BERYLLIUM 100 

3. HEALTH EFFECTS 

beryllium were identified. The smaller fraction was presumably bound to plasma organic acids. In the 

larger fraction, the beryllium sulfate was converted to beryllium phosphate, which formed aggregates 

associated with plasma globulins, presumably α-globulin. The size of the aggregates appeared to increase 

with increasing beryllium sulfate doses. 

3.4.3 Metabolism 

Beryllium and its compounds are not biotransformed, but soluble beryllium salts are partially converted to 

less soluble forms in the lung (Reeves and Vorwald 1967). 

3.4.4 Elimination and Excretion 

3.4.4.1 Inhalation Exposure 

In eight men accidentally exposed to .8 ng beryllium/m3

 as beryllium chloride 4–6 hours/day for 10 days, 

urinary levels were four times higher than the average levels of .1.0 ng beryllium/g in unexposed 

individuals (Stiefel et al. 1980). Accidental exposure of 25 individuals to beryllium dust for 10–20 hours 

increased serum levels to 3.5 ppb beryllium 1 day after exposure, compared to .1 ppb for unexposed 

individuals (Zorn et al. 1986). Serum levels returned to normal 2–8 weeks after exposure. The biological 

half-life was estimated to range from 2 to 8 weeks. 

Beryllium oxide deposited in the lungs of rats was cleared in a biphasic manner (Rhoads and Sanders 

1985). In the first phase, 30% of the total lung burden was cleared; the half-life was 2.5 days. In the 

second phase, the remaining 70% of the beryllium in the lung was cleared with a half-life of 833 days. 

The whole body clearance yielded a single-phase exponential curve with a half-life of 356 days. Rats 

exposed to beryllium oxide were able to clear 12 and 21% (female and male, respectively) of the alveolar 

lung burden within 63 days of exposure (Sanders et al. 1975). Hamsters, however, cleared 38 and 45% 

(female and male, respectively) of the beryllium in the alveoli. The study indicates that male rats are 

better able to clear beryllium particles from the lungs than female rats are. The biological half-life for 

beryllium oxide in the rat lung was estimated to be .6 months. Approximately 95% of the beryllium was 

excreted through the feces. Rats and guinea pigs exposed to 2–40 mg beryllium/m3

 as beryllium nitrate 

for 16 hours had increased concentrations of urinary beryllium (300 ng beryllium/g), compared to normal 

concentrations (2.1 ng beryllium/g) (Stiefel et al. 1980). Rats exposed to radioactive beryllium 

compounds excreted 92% of the dose in 408 hours (Zorn et al. 1977). In dogs exposed only via nose to 
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3. HEALTH EFFECTS 

10 mg beryllium/m3 as beryllium oxide calcined at 500 or 1,000 EC (the solubility of beryllium oxide 

decreases as the temperature at which it is calcined increases) for sufficient durations to result in low 

(.5 μg beryllium/kg) initial lung burdens and high (36–64 μg beryllium/kg) initial lung burdens, there 

were no differences in whole-body retention with regard to initial lung burdens (Finch et al. 1990). 

Whole-body clearance after exposure to beryllium oxide calcined at 500 EC was described by a twocomponent, negative exponential function. The short-term component accounted for 59% of the initial 

lung burden and had a half-life of 54 days. The long-term component accounted for 41% of the initial 

lung burden and had a half-life of >1,000 days. The long-term component may have represented 

beryllium that dissolved from beryllium oxide particles and bound to extrapulmonary compartments, such 

as, bone and liver. Whole-body clearance after exposure to beryllium oxide calcined at 1,000 EC was 

described by a single-component negative exponential function with a half-life of 310 days. Clearance 

from the lung was more rapid and greater amounts were translocated to the liver, blood, and skeleton in 

the dogs exposed to beryllium calcined at the lower temperature than in dogs exposed to beryllium 

calcined at the higher temperature. However, lung clearance of both was described by a singlecomponent negative exponential function. Clearance half-lives were 64 days for 500 EC calcined 

beryllium oxide and 240 days for 1,000 EC calcined beryllium oxide. Fecal excretion predominated at 

early times after exposure to either beryllium oxide aerosols, and at all times for 1,000 EC calcined 

beryllium oxide. Dogs exposed to beryllium oxide calcined at 500 EC excreted a significantly (p<0.05) 

greater total percentage of the initial lung burden of beryllium than dogs exposed to beryllium calcined at 

the higher temperature by 180 days. Thus, beryllium oxide calcined at 500 EC was cleared more rapidly 

than beryllium oxide calcined at 1,000 EC. This is consistent with the fact that more soluble beryllium 

compounds are cleared faster than relatively insoluble beryllium compounds because the solubility of 

beryllium oxide decreases as the temperature at which it is calcined increases. Although clearance of 

beryllium oxide calcined at the lower temperature was relatively fast during the first few days after 

exposure due to mucociliary clearance, later clearance may result from slow translocation of 

tracheobronchial lymph nodes, macrophage clearance from the pulmonary to the tracheal regions, and 

pulmonary solubilization of beryllium followed by mobilization through blood to liver and bone or 

excretion in urine. Beryllium decreased the clearance rate of radioactive plutonium oxide from the lungs 

of rats 60 and 90 days after exposure to beryllium oxide (Sanders et al. 1975). Inhalation exposure to 

beryllium may decrease the overall rate of lung clearance by damaging alveolar macrophages. 
BERYLLIUM 102 

3. HEALTH EFFECTS 

3.4.4.2 Oral Exposure 

No studies were located regarding excretion in humans after oral exposure to beryllium or its compounds. 

Animals exposed to oral doses of beryllium or its compounds excrete the greatest percentage of the dose 

via the feces, which indicates that beryllium is poorly absorbed by the gastrointestinal tract. Analysis of 

the excreta of rats exposed to 0.019 and 0.190 mg beryllium/kg/day as beryllium sulfate in the drinking 

water indicated that $99% of the dose was excreted in the feces and <0.5% was excreted in the urine 

(Reeves 1965). The excretion pattern of beryllium in the feces reached steady-state after 9 weeks (Reeves 

1965). Similarly, excretion of beryllium occurred mainly via the feces of rats exposed to 0.3, 2.8, and 

31 mg beryllium/kg/day as beryllium sulfate in the diet for 2 years (Morgareidge et al. 1975). The feces 

contained 10.7 ppm and the urine 29.7 ppb of the 0.3 mg beryllium/kg/day dose, and a similar pattern was 

observed with the other doses. Rats, monkeys, mice, and dogs orally exposed to radioactive beryllium 

chloride excreted 98% of the dose via the feces (Furchner et al. 1973). 

3.4.4.3 Dermal Exposure 

No studies were located regarding excretion in humans or animals after dermal exposure to beryllium or 

its compounds. 

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. 
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3. HEALTH EFFECTS 

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 

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) is 

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. 

Figure 3-3 shows a conceptualized representation of a PBPK model. 
Skin 

Kidney 

Richly 

perfused 

tissues 

Slowly 

perfused 

tissues 

Fat 

Liver 

Lungs 

A 

R 

T 

E 

R 

I 

A 

L 

B 

L 

O 

O 

D 

V 

E 

N 

O 

U 

S 

B 

L 

O 

O 

D 

GI 

Tract 

Vmax Km 

Urine 

Chemicals in air 

Inhaled chemical Exhaled chemical 

Ingestion 

Feces 

contacting skin 

Source: adapted from Krishnan et al. 1994 

Note: This is a conceptual representation of a physiologically based pharmacokinetic (PBPK) model for a 

hypothetical chemical substance. The chemical substance is shown to be absorbed via the skin, by 

inhalation, or by ingestion, metabolized in the liver, and excreted in the urine or by exhalation. 

BERYLLIUM 104 

3. HEALTH EFFECTS 

Figure 3-3. Conceptual Representation of a Physiologically Based
 

Pharmacokinetic (PBPK) Model for a
 

Hypothetical Chemical Substance
 
BERYLLIUM 105 

3. HEALTH EFFECTS 

No PBPK modeling studies were located for beryllium. 

3.5 MECHANISMS OF ACTION 

3.5.1 Pharmacokinetic Mechanisms 

The absorption of inhaled beryllium depends on a number of factors, including physical and chemical 

properties of the particles (e.g., size, solubility) and the activity of alveolar macrophages. Following 

deposition, beryllium is slowly cleared from the lung; clearance half-lives range from days to years in 

animals. Beryllium clearance from the lungs is biphasic, the initial phase is rapid and involves clearance 

via the mucociliary escalator. Approximately 30% of the total lung burden was cleared during the first 

phase with a half-life of 2.5 days (Rhoads and Sanders 1985). The second phase is slower, involving 

translocation to the tracheobronchial lymph nodes, alveolar macrophage clearance, and solubilization. 

The half-life for this phase was 833 days (Rhoads and Sanders 1985). Beryllium is poorly absorbed 

through the gastrointestinal tract; <1% of the dose is absorbed (Furchner et al. 1973; Reeves 1965). It is 

also poorly absorbed through intact skin (Petzow and Zorn 1974; Williams et al. 1987). 

Absorbed beryllium is distributed throughout the body via blood, with the highest concentrations in the 

liver and skeleton (Finch et al. 1990; Furchner et al. 1973; Morgareidge et al. 1975; Stokinger et al. 

1950). Beryllium has been detected in breast milk (Krachler et al. 1999a), but the relationship between 

beryllium exposure and breast milk levels has not been established. 

The primary routes of elimination of absorbed beryllium is urine and feces. In rats and dogs, whole body 

clearance of inhaled beryllium follows a single-phase exponential curve with a half-life of 300–400 days 

(Finch et al. 1990; Rhoads and Sanders 1985). 

3.5.2 Mechanisms of Toxicity 

The respiratory tract is the primary target of beryllium toxicity following inhalation exposure. In humans, 

chronic beryllium disease and lung cancer are the principal effects observed. In animals, the respiratory 

tract effects include emphysema, pneumonitis, and lung cancer. Chronic beryllium disease begins as a 

sensitizing cell-mediated response to beryllium antigen that progresses to noncaseating granulomatous 

lung disease. Although the mechanism has not been fully elucidated, a number of recent studies using 

bronchoalveolar lavage (BAL) fluid from individuals with chronic beryllium disease provide information 
BERYLLIUM 106 

3. HEALTH EFFECTS 

on some of the components of the toxic sequence. Beryllium, acting as a hapten, interacts with antigen 

presenting cells in the lungs (i.e., alveolar macrophages) resulting in a beryllium-peptide becoming 

physically associated with a major histocompatability (MHC) class II molecule (Newman 1996b; Saltini 

et al. 1989). The MHC class II-beryllium-peptide complex is recognized by the T lymphocyte receptor, 

with the help of CD4+

 molecules. This interaction triggers CD4+ T lymphocyte activation and 

proliferation. There is evidence to suggest that there is a selective expansion of certain CD4+

 lymphocyte 

subsets. In a study by Fontenot et al. (1998), a number of individuals with chronic beryllium disease had 

an increase in the percentage of T cell receptor (TCR) variable β3 regions (Vβ3). Further work by this 

group showed that in four of five individuals with chronic beryllium disease, expansions within the 

Vβ3 region resulted in homologous or identical CDR3 amino acid sequences (Fontenot et al. 1999). The 

expansion of the CDR3 motif appeared to be unique to chronic beryllium disease. 

The antigen-specific inflammatory response to beryllium is a cell-mediated process orchestrated by 

cytokines. The results of several studies support the role of cytokines in chronic beryllium disease. 

Using alveolar macrophages present in BAL fluid from individuals with chronic beryllium disease, Bost 

et al. (1994) found elevated mRNA levels for tumor necrosis factor α (TNF-α) and interleukin 

(IL)-6 cytokines, as compared to levels in normal subjects. Additionally, TNF-α levels in the BAL fluid 

were higher. Another study found that the addition of beryllium to a culture of BAL cells from chronic 

beryllium disease patients, resulted in increases in the TNF-α, IL-6, IL-2, and interferon-gamma (IFN-γ) 

(Tinkle et al. 1996). Although for many inflammatory diseases IL-10 inhibits antigen-induced T 

lymphocyte proliferation, it does not play a role in chronic beryllium disease (Tinkle et al. 1996a). In 

chronic beryllium disease, as in other delayed-type hypersensitivity diseases, IL-2 plays an important role 

in the T lymphocyte proliferation and the regulation of IFN-γ (Tinkle et al. 1997). BAL cells from 

control subjects did not show any measurable spontaneous or beryllium sulfate-stimulated release of IL-2, 

α-sIL-2R (α subunit of the soluble IL-2 receptor), IL-4, or IFN-γ. Beryllium sulfate stimulation of BAL 

cells from chronic beryllium disease subjects resulted in the production of IL-2, α-sIL-2R, and IFN-γ, but 

not IL-4. In the absence of beryllium sulfate stimulation, the response was the same as in controls. 

Although IL-2 has a dose-dependent role in T lymphocyte proliferation, T lymphocyte proliferation is 

only partially dependent on it. Beryllium sulfate stimulated T lymphocyte proliferation remained 

elevated in the presence of anti-IL-2 antibodies. INF-γ levels were also decreased in the presence of 

anti-IL-2 antibodies suggesting that it is also partially dependent on IL-2. 

There appears to be a genetic factor associated with susceptibility to chronic beryllium disease. The 

MHC class II molecules play a critical role in the T lymphocyte proliferation and the development of 
BERYLLIUM 107 

3. HEALTH EFFECTS 

chronic beryllium disease; thus, MHC class II genes (human leukocyte antigen, HLA-DR, DQ, DP) 

probably play a role in susceptibility to the disease. Analysis of the MHC class II genes shows a biased 

usage of the HLA-DPB1 gene alleles in individuals with chronic beryllium disease (Richeldi et al. 1993, 

1997; Wang et al. 1999). Genetic susceptibility to chronic beryllium disease is discussed in greater detail 

in Section 3.10. 

3.5.3 Animal-to-Human Extrapolations 

As reviewed in EPA (1998) and Finch et al. (1996), a number of animal models of human chronic 

beryllium disease have been developed, but none of the models to date mimic all aspects of the human 

disease. Numerous studies in dogs, monkeys, and rats have reported granulomatous inflammation in the 

lungs. However, the lung lesions do not histopathologically resemble chronic beryllium disease in 

humans, the effects are transient, or are not consistently associated with beryllium-specific immune 

responses. Recent studies in mice (Huang et al. 1992; Nikula et al. 1997) suggest that mice may be an 

appropriate model. In the model developed by Huang et al. (1992), mice were preimmunized with 

beryllium sulfate and then administered a single intratracheal dose of beryllium sulfate. A number of 

aspects of this model mimicked chronic beryllium disease, influx of CD4+

 T lymphocytes in to the lungs, 

sensitization of T lymphocytes to beryllium, interstitial inflammation, and granuloma formation. 

However, these effects were observed at 8 months and were resolved by 10 months. The study by Nikula 

et al. (1997), in which mice received a 90-minute nose-only exposure to beryllium metal, also found 

many similarities between effects observed in mice and human chronic beryllium disease. The study 

authors concluded that this mouse model can be used to study the influence of dose, exposure pattern, and 

physicochemical form of beryllium on the development of chronic beryllium disease. A comparison of 

the histologic characteristics of beryllium-induced disease in humans and mice is presented in Table 3-5. 

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 
BERYLLIUM 108 

3. HEALTH EFFECTS 

Table 3-5. Histologic Characteristics of Beryllium-induced Disease in Mice and
 

Humansa
 

Histologic findings Mice Humans 

Interstitial cellular infiltration of 

macrophages, lymphocytes, 

and variable numbers of plasma 

cells 

Mild to moderate Moderate to marked 

Granulomas Present; poorly formed Variable; absent to poorly 

formed to well formed 

Giant cells Numbers variable; may be 

scattered or associated with 

granulomas 

Numbers variable; may be 

scattered or associated with 

granulomas 

Cholesterol clefts Numerous and often seen within 

giant cells 

Numerous and often seen within 

giant cells 

Interstitial fibrosis Present in 75% of cases; 

minimal to mild 

Present in large percentage of 

cases; minimal to mild in 50% 

and moderate to marked in 50% 

Calcific inclusions Absent Present in approximately 55% 

of cases 

Hyalinzed nodules Absent Present in lung or hilar lymph 

nodes of 40% of cases 

Interstitial compact aggregates 

of lymphocytes 

Present Not described 

Beryllium Metal evident in H&E sections Increased tissue levels found by 

spectrographic and chemical 

analysis 

a

Taken from Nikula et al. (1997) 
BERYLLIUM 109 

3. HEALTH EFFECTS 

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 

Environmental Protection Agency (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), which in 1998 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 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). 

There are no data to assess whether exposure to beryllium will adversely affect the endocrine system. 

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. 
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3. HEALTH EFFECTS 

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 

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 
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3. HEALTH EFFECTS 

alveoli being less developed, which results in a disproportionately smaller surface area for alveolar 

absorption (NRC 1993). 

Data on the toxicity of beryllium in children is limited to a case report of a child diagnosed with chronic 

beryllium disease (Eisenbud et al. 1948b). The child lived near a beryllium manufacturing facility. The 

only available studies on young animals are the beryllium carbonate dietary studies that found beryllium 

rickets in young rats (Guyatt et al. 1933; Jacobson 1933; Kay and Skill 1934). The observed skeletal 

effects are not due to a direct effect of beryllium on the bone, but rather an interaction between beryllium 

carbonate and dietary phosphorus. The potential of beryllium to induce developmental effects has not 

been adequately investigated. A chronic study did not find developmental effects (gross and skeletal 

malformations, fetal survival, and fetal body weights were examined) in dogs exposed to beryllium 

sulfate in the diet (Morgareidge et al. 1976). However, intratracheal and intravenous exposure studies 

have found increases in fetal/neonatal mortality, internal abnormalities, and behavioral abnormalities in 

rat and mouse offsprings (Bencko et al. 1979; Mathur et al. 1987; Selivanova and Savinova 1986; Tsujii 

and Hoshishima 1979). More details about these studies can be found in Chapter 2 and Section 3.2.2.6. 

No human or animal data were located that examined possible age-related differences in the 

toxicokinetics of beryllium. There are no data on the toxicokinetic properties of beryllium in children or 

immature animals. The results of a study by Krachler et al. (1999a) suggests that beryllium is transferred 

across the placenta and via maternal milk. Beryllium levels in the umbilical cord sera and in colostrum 

were higher than maternal sera levels. 

Subsequent sections of this chapter (Sections 3.8, 3.10, and 3.11) discuss the available information on 

biomarkers, interactions, and methods for reducing toxic effects. The available information is from adults 

and mature animals; no child-specific information was identified. It is likely that this information will 

also be applicable to children. 

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 
BERYLLIUM 112 

3. HEALTH EFFECTS 

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 beryllium 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 beryllium are discussed in Section 3.8.2. 

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 Beryllium 

There are several tests for measuring beryllium in biological fluids and tissues (Frame and Ford 1974; 

Foreman et al. 1970; Hurlburt 1978; IARC 1980; Martinsen and Thomassen 1986; Paschal and Bailey 

1986; Shan et al. 1989). These include measurement of beryllium levels in the blood and urine. 

Information regarding normal background levels of beryllium and tissue levels associated with exposure 
BERYLLIUM 113 

3. HEALTH EFFECTS 

levels are limited or unreliable. Normal background levels of 1 ng beryllium/g (1 ppb) for blood (Stiefel 

et al. 1980; Zorn et al. 1986), 0.28–1 μg/L for urine (Paschal et al. 1998; Stiefel et al. 1980), and of 

0.02 μg beryllium/g (0.02 ppm) for lung tissue (Kanarak et al. 1973) have been reported. Average 

beryllium levels in human tissues have been measured as follows: 0.21 ppm in lungs; 0.08 ppm in brain; 

0.07 ppm in both kidney and spleen; 0.04 in each of liver, muscle, and vertebrae; 0.03 ppm in heart; and 

0.02 in bone (Meehan and Smythe 1967). However, it was not clear whether these organ samples were 

obtained at biopsy or autopsy or whether the subjects had been exposed occupationally or 

environmentally in the compilation by Meehan and Smythe (1967). 

Background urinary levels of beryllium were determined to be .1.0 μg beryllium /L using flameless 

atomic absorption spectroscopy (Stiefel et al. 1980). Beryllium levels in urine were analyzed in eight 

laboratory workers and compared to the levels of beryllium in the laboratory atmosphere for 30 days after 

an accidental leakage of beryllium chloride. Figure 3-4 represents urinary levels versus atmospheric 

levels. The urinary levels appear to be directly proportional to atmospheric levels at #8 ng/m3

. Based on 

serum levels of beryllium in workers accidentally exposed, the biological half-life was estimated to be 

2–8 weeks (Zorn et al. 1986). These are the only available data that associate airborne beryllium levels 

with urinary levels in humans. A sampling of 500 urine samples collected during the NHANES III study, 

suggested that background levels of beryllium in the urine may be lower; the mean urinary level was 

0.28 μg beryllium/L (Paschal et al. 1998). Nonetheless, urinary excretion of beryllium is irregular and 

not useful for diagnostic purposes (Reeves 1986). 

Biopsy tissue has been analyzed to determine beryllium concentrations in the body. Lung tissue of two 

employees of a beryllium extraction and processing plant, where beryllium concentrations exceeded the 

recommended standards of 2 μg beryllium/m3

 for an 8-hour day and 25 μg beryllium/m3 for a 30-minute 
Figure 3-4. Relationship Between Urine Level of Beryllium and Air Concentratio

5 4 3 2 1 0 

0 1 2 3 4 5 6 7 8 9 

Air (ng Be/m3) 

*Source: Stiefel et al. 1980 
BERYLLIUM 115 

3. HEALTH EFFECTS 

maximum level, contained 0.18 and 0.65 μg beryllium/g dry weight compared to the normal level of 

0.02 μg beryllium/g (Kanarek et al. 1973). The subject with the higher beryllium level did not have lung 

lesions; however, the subject with the lower beryllium level had granulomas. Thus, beryllium levels in 

lung biopsies indicate exposure to beryllium but may not confirm the presence of chronic beryllium 

disease. The presence of beryllium in lung tissue also will not indicate how recently the exposure 

occurred because the clearance of beryllium from the lungs depends upon the solubility of the beryllium 

compound (see Section 3.3.4.1). Biomarkers of oral or dermal exposure to beryllium were not located, 

probably because very little beryllium is absorbed after exposure by these routes (see Section 3.4.1). 

3.8.2 Biomarkers Used to Characterize Effects Caused by Beryllium 

The lung is the most sensitive target organ of beryllium exposure. As a consequence of long term 

exposure to beryllium, lung function decreases. This decrease has been measured by spirometry, such as 

forced expiratory volume in 1 second, maximum breathing capacity, maximum mid-expiratory flow, and 

vital capacity (Andrews et al. 1969; Kriebel et al. 1988a, 1988b). Blood gases such as carbon dioxide 

tension, oxygen tension, alveolar oxygen tension, alveolar carbon dioxide tension, and carbon monoxide 

diffusion capacity have also been analyzed. 

Radiographic examinations revealed opacities in the lung following chronic exposure to beryllium 

(Kanarek et al. 1973). X-rays have been used to determine three stages of chronic beryllium poisoning: a 

fine diffuse granularity in the lungs, followed by a diffuse reticular pattern, followed by the appearance of 

distinct nodules. However, x-ray results cannot distinguish between chronic beryllium disease and 

sarcoidosis. A patch test using soluble beryllium salts was evaluated in 32 patients with known chronic 

beryllium disease (Curtis 1959). The patch test was positive in all 32 patients and negative in 16 of 

18 patients with lung diseases other than chronic beryllium disease, indicating that the patch test may be 

useful in the diagnosis of chronic beryllium disease. However, the patch test using soluble beryllium 

compounds itself may be sensitizing and may exacerbate the condition in patients with chronic beryllium 

disease (Cotes et al. 1983; Epstein 1983; Stoeckle et al. 1969; Tepper 1972). Therefore, this method is 

not recommended as a diagnostic tool. Analysis of secretions and cells of the lower respiratory tract 

obtained by bronchoalveolar lavage is useful for detecting granulomatous lung disease; however, it alone 

cannot distinguish chronic beryllium disease from sarcoidosis (James and Williams 1985). The presence 

of beryllium in the bronchoalveolar fluid, however, would aid the diagnosis. 
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Because chronic beryllium disease is caused by an immune reaction to beryllium, several tests have been 

developed to assess beryllium hypersensitivity. The most commonly used test is the beryllium 

lymphocyte proliferation test (BeLPT). This test, originally referred to as the lymphocyte blast 

transformation test (LTT or LBTT), measures cell proliferation via thymidine incorporation in cultured 

cells in the presence or absence of beryllium salts. Both peripheral blood cells and bronchioalveolar 

lavage cells can be used in the BeLPT. In early studies, abnormal blood BeLPT results were found in 

100% of the subjects with chronic beryllium disease (Williams and Williams 1982, 1983), normal results 

in all individuals who were suspected of having chronic beryllium disease (Williams and Williams 1983), 

and abnormal results in approximately 2% of the healthy beryllium workers (Williams and Williams 

1983). Despite these results, the blood BeLPT test was not widely used because it was very difficult to 

perform and not very reproducible. Refinement of the test methodology resulted in a more reproducible 

test that could be used as a screening tool (Newman 1996a). A number of large-scale screening studies 

have utilized this test for identifying beryllium sensitized workers (Kreiss et al. 1993a, 1996, 1997; 

Newman et al. 2001; Stange et al. 2001). In these studies, the majority (53–86%) of the workers with 

consistently abnormal blood BeLPT results were also diagnosed as having chronic beryllium disease. 

Using the blood BeLPT to screen workers for beryllium sensitization and chronic beryllium disease is not 

foolproof; Kreiss et al. (1993a, 1996) found a small percentage of workers with chronic beryllium disease 

and normal or inconsistent blood BeLPT results. Deubner et al. (2001a) assessed the predictive value of 

the blood BeLPT as a screening tool for chronic beryllium disease among 129 beryllium workers. The 

incidences of chronic beryllium disease among workers with a single unconfirmed abnormal blood 

BeLPT result, workers with confirmed abnormal blood BeLPT results, and workers with first-time double 

abnormal blood BeLPT results were 7/19 (37%), 34/75 (45%), and 17/35 (49%), respectively. One 

limitation of the blood BeLPT is high inter- and intra-laboratory variability. Using split blood samples, 

Stange et al. (1996b) found an 85–96% agreement rate among three laboratories; however, the agreement 

rate was only 21–33% for positive blood BeLPT results. Similarly, Deubner et al. (2001a) found poor to 

moderate agreement in blood BeLPT results among three laboratories. 

3.9 INTERACTIONS WITH OTHER CHEMICALS 

Mortality rates were lower if rats exposed to 2.59 mg beryllium/m3

 as beryllium sulfate were injected 

daily with ferric ammonium citrate beginning 4 days prior to beryllium exposure (Sendelbach and 

Witschi 1987a). The protective action of ferric ammonium citrate may be related to the ability of 

beryllium to form a complex with citrate (Reeves 1986). In addition, the protective action of iron on 

beryllium toxicity may be related to the ability of iron to increase ferritin synthesis, making more ferritin 
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available to bind with beryllium (Lindenschmidt et al. 1986). Ferritin chelates with beryllium to protect 

against the inhibition of phosphoglucomutase (Joshi et al. 1984). 

Ingested soluble beryllium compounds may interact with phosphate to form insoluble beryllium 

phosphate particles that are sequestered in Kupffer cells of the liver (Tepper 1972). Diffusion of 

beryllium from the deposited particulates may cause damage to these cells and necrosis of the liver. 

Intravenous injection of rats or mice with the ammonium salt of aurine tricarboxylic acid increased the 

survival of both species that were injected intravenously with lethal doses of beryllium sulfate (White et 

al. 1951). The protective effect was observed when the aurine tricarboxylic acid was administered from 

1 hour before to 8 hours after injection of beryllium sulfate. The protective effect was attributed to the 

ability of aurine tricarboxylic acid to complex with the beryllium ion, thereby reducing the amount of 

beryllium ion available to induce tissue injury. 

Co-exposure of Chinese hamster ovary cells to beryllium sulfate and x-rays resulted in an increased rate 

of chromatid-type exchanges compared to the rates resulting from exposure to beryllium sulfate or x-rays 

alone (Brooks et al. 1989). The increase was multiplicative rather than additive. Experiments on cell 

cycle kinetics suggested that the multiplicative interaction occurs only in cells in the S and G2 stages. 

3.10 POPULATIONS THAT ARE UNUSUALLY SUSCEPTIBLE 

A susceptible population will exhibit a different or enhanced response to beryllium than will most persons 

exposed to the same level of beryllium 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 beryllium, or compromised function of organs 

affected by beryllium. Populations who are at greater risk due to their unusually high exposure to 

beryllium are discussed in Section 6.7, Populations With Potentially High Exposures. 

There are strong data to suggest that there is genetic susceptibility factor that may predispose certain 

individuals to development of chronic beryllium disease. A human leukocyte antigen (HLA) class II 

marker has been strongly associated with chronic beryllium disease. Studies conducted by Fontenot et al. 

(2000) and Lombardi et al. (2001) suggest that the HLA-DP allele, in particular alleles with HLA-DP 

containing Glu at DP69, are involved in the presentation of beryllium to CD4+ T cells, which are involved 

in the pathogenesis of chronic beryllium disease. Richeldi et al. (1993) found a higher frequency of 
 

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allelic variants of the HLA-DP gene coding for a glutamate in position 69 of HLA-DPB1 chain
 

(HLA-DPB1 Glu69) among individuals with chronic beryllium disease than in beryllium-exposed
 

individuals without the disease. The HLA-DPB1 Glu69 DNA marker was found in 5 of 6 beryllium
 

workers with chronic beryllium disease, 0 of 2 beryllium-sensitized individuals without disease and 36 of
 

119 (30%) unsensitized beryllium-exposed individuals (Richeldi et al. 1997).
 

Further analysis by Wang et al. (1999) found the Glu69 marker on the HLA-DBP1 gene was not very
 

predictive of chronic beryllium disease (predictive value of 0.36). However, the presence of the relatively
 

rare HLA-DP allele, HLA-non*0201 DPB1 Glu69, had a predictive value of 0.57. Wang et al. (1999) also
 

found a higher percentage of homozygous Glu69 carriers in the chronic beryllium disease group as
 

compared to controls. The study authors estimated that carriers of the Glu69/Glu69 markers or
 

non-*0201Glu69 allele accounted for 85% of the chronic beryllium disease cases and only 16% of
 

unaffected beryllium-exposed individuals. Additional studies by this group found that most beryllium
 

sensitized individuals without chronic beryllium disease also carried rare HLA-non*0201 Glu69
 

DPB1 alleles (Wang et al. 2001).
 

Stubbs et al. (1996) also found allelic differences in the DR isotype of class II HLAs. The
 

HLA-DRB1 alleles associated with beryllium sensitization were *0103, *09, *1302, *0403, and *0302. 

It is likely that chronic beryllium disease is a multigenetic disease with a number of genetic factors
 

contributing to the development of an immune response to beryllium.
 

A case control study by Maier et al. (1999) was designed to assess whether polymorphisms in the
 

angiotensin converting enzyme (ACE) were associated with chronic beryllium disease and chronic
 

beryllium disease severity. No statistically significant associations between ACE genotype and chronic
 

beryllium disease were found in the comparisons of individuals with chronic beryllium disease to
 

beryllium-exposed controls or nonberyllium exposed controls. 

Animal data support the human data that genetically determined cellular immune mechanisms may be
 

involved in chronic beryllium disease, as indicated by studies in different strains of guinea pigs and mice. 

Intratracheal instillation of beryllium oxide (calcined at 560 EC) resulted in the development of
 

granulomatous lung disease in outbred Hartley and in strain 2 guinea pigs, but not in strain 13 guinea pigs
 

(Barna et al. 1981; 1984). Granulomatous lung disease also was produced in the F1 offspring of mated
 

strain 2 and strain 13 guinea pigs, but the severity was milder in the hybrid strain than in the strain
 

2 guinea pigs (Barna et al. 1984). In addition, when guinea pigs exposed intradermally or intratracheally
 
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to beryllium oxide were challenged by dermally applied beryllium sulfate, the strain 2 and the F1 guinea 

pigs showed positive skin tests for delayed-type hypersensitivity, while strain 13 guinea pigs did not. 

Granulomatous lung disease was also induced in strain A/J (H-2a haplotype) mice, but not in BALB/c 

(H-2d haplotype) or C57BL/6 (H-2b haplotype) mice, after intratracheal injection of beryllium sulfate, 

suggesting that genetic differences at the H-2 major histocompatibility gene complex may account for the 

differential responses to beryllium sulfate in mice (Huang et al. 1992). These results suggest that 

genetically determined factors may make some humans more susceptible to chronic beryllium disease. 

Animal data indicate that females may be more susceptible than males to the effects of beryllium. Female 

rats exposed to 0.034 mg beryllium/m3

 as beryllium sulfate for 72 weeks had higher mortality rates and 

more severe weight loss than males (Reeves et al. 1967). Female rats exposed to #31 mg 

beryllium/kg/day as beryllium sulfate in the diet for 2 years developed a transient glucosuria; renal effects 

were not observed in males (Morgareidge et al. 1975). The distribution of beryllium in body tissue in 

female (bred and nonbred) and male rats exposed intratracheally to 0.6 mg beryllium/kg as radioactive 

beryllium oxide revealed the highest concentrations (other than in the lung) in the liver of female rats and 

in the kidney of male rats (Clary et al. 1975). This corroborates the findings of Clary et al. (1972) which 

suggest that translocation of beryllium from bone to liver eventually causes a systemic disease 

characterized by weight loss and liver necrosis. The study involves intratracheal exposure of guinea pigs 

and mice to radioactive beryllium oxide after hormone biosynthesis is inhibited by metyrapone injection. 

The results indicate that altered adrenal hormone synthesis shifts beryllium concentrations from bone to 

liver, causing weight loss. Therefore, any adverse effect on the adrenal gland may profoundly affect the 

course of beryllium disease, and a combination of adrenal dysfunction and compromised liver function 

could exacerbate beryllium disease. Therefore, people with lowered adrenal and/or liver functionality 

may be unusually susceptible to the effects of beryllium. 

3.11 METHODS FOR REDUCING TOXIC EFFECTS 

This section will describe clinical practice and research concerning methods for reducing toxic effects of 

exposure to beryllium. 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 beryllium. 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 beryllium: 
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Ellenhorn MJ, Schonwald S, Ordog G, et al., eds. 1997. Ellenhorn’s Medical Toxicology: Diagnosis 

and Treatment of Human Poisoning. Second Edition. Baltimore, MD: Williams & Wilkins, 1546-1548. 

Haddad LM, Shannon MW, Winchester JF, eds. 1998. Clinical Management of Poisoning and Drug 

Overdose. Third Edition. Philadelphia, PA: WB Saunders, 792. 

3.11.1 Reducing Peak Absorption Following Exposure 

Human exposure to beryllium and its compounds occurs by inhalation, ingestion, or dermal contact. The 

inhalation route is of greatest concern for systemic effects because beryllium and its compounds are 

poorly absorbed after ingestion and dermal contact. General recommendations for reducing absorption of 

beryllium following acute exposure have included removing the individual from the contaminated area 

and removing contaminated clothing. Although beryllium is poorly absorbed from the gastrointestinal 

tract, administration of milk or water has been suggested to reduce the possibility of stomach irritation 

(HSDB 2000). Chronic granulomas observed following dermal exposure are surgically removed (HSDB 

2000). Thorough washing of the skin or eyes is indicated in the case of dermal or ocular exposure, 

especially to irritating beryllium compounds, such as beryllium fluoride. 

3.11.2 Reducing Body Burden 

Beryllium is widely but slowly distributed following inhalation exposure. The highest concentration of 

beryllium was found in bone (13.5%) of rats following 3 hours of exposure to beryllium sulfate or 

beryllium chloride (Zorn et al. 1977). The percentage of beryllium in the bone was still high (6.8%) 

compared with other tissues following 408 hours of exposure. After inhalation exposure, beryllium that is 

not absorbed into the bloodstream is retained in the lung (see Section 3.4.4.1). Insoluble beryllium 

compounds, such as beryllium oxide, are retained in the lungs longer than soluble compounds and are 

associated with chronic beryllium disease. Although beryllium compounds are poorly absorbed from the 

gastrointestinal tract (see Section 3.4.1.2), the portion that is absorbed appears to preferentially 

accumulate in bone (Furchner et al. 1973; Morgareidge et al. 1975; Reeves 1965). In addition, relatively 

high levels of beryllium accumulated in the spleen and liver of rats after intravenous injection of 

beryllium sulfate (Lindenschmidt et al. 1986). 

A series of studies by Mathur and associates have examined the effectiveness of several agents in 

reducing beryllium body burden following parenteral exposure (no additional information on exposure 

route was provided). Decreases in blood, liver, kidney, and/or spleen beryllium levels were observed in 

rats administered a single or repeated doses of beryllium followed by a 2- to 10-day exposure to Liv-52, 
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3. HEALTH EFFECTS 

an alternative medicine (Mathur et al. 1994) or 5 days of N-(2-hydroxyethyl)ethylene diamine triacetic 

acid (HEDTA) (Mathur et al. 1993), calcium disodium ethylenediamine tetraacetic acid (CaNa-EDTA) 

(Mathur et al. 1993), 4,5-dihydroxy-1,3-benzene disulfonic acid (tiron) (Shukula et al. 1998) 

meso-2,3-dimercaptosuccinic acid (DMSA) (Flora et al. 1995), or 2,3-dimercaptopropane 1-sulfonate 

(DMPS) (Flora et al. 1995), but not after calcium trisodium diethylene triamine pentaacetic acid 

(CaNA-DTPA) (Mathur et al. 1993) or succinic acid (Shukula et al. 1998). For absorbed beryllium, 

administration of chelating agents such as aurine tricarboxylic acid increases the urinary excretion of 

beryllium in animals (Venugopal and Luckey 1978). However, metal chelating agents available for use in 

human clinical medicine have not been shown to be effective in reducing the toxicity of beryllium (Hall 

and Rumack 1992). Since chronic berylliosis is associated with the retention of unabsorbed beryllium 

compounds in the lungs, enhancing the clearance of beryllium from the lungs, perhaps by 

bronchoalveolar lavage, might prevent or reduce the severity of chronic beryllium disease. However, at 

this time there are no established methods for reducing the lung burden. 

3.11.3 Interfering with the Mechanism of Action for Toxic Effects 

As discussed in Section 3.9, pretreatment of rats with ferric ammonium citrate reduces mortality rates 

following inhalation exposure to beryllium (Sendelbach and Witschi 1978a). This protective effect has 

been attributed to sequestering of beryllium either through formation of a beryllium-citrate complex 

(Reeves 1986), or by induced ferritin (Lindenschmidt et al. 1986). Aurine tricarboxylic acid may reduce 

mortality by a similar mechanism (White et al. 1951). Neither of these treatments has undergone clinical 

trial in humans. 

Parenteral administration of beryllium nitrate results in decreased hemoglobin, blood glucose, and serum 

protein levels, decreased serum alkaline phosphatase levels, increased serum transaminase activities, and 

degeneration and necrosis in the liver, kidney, and spleen. Administration of Liv-52, HEDTA, 

CaNa-EDTA, tiron or DMPS resulted in an improvement of these effects (Flora et al. 1995; Mathur et al. 

1993, 1994; Shukula et al. 1998). The effectiveness of these treatments at lower body burdens or in 

humans is not known. As discussed in Section 3.2.1.2, the respiratory tract can be severely affected by 

inhalation of dust containing beryllium compounds. Inhalation exposure to high concentrations of soluble 

beryllium compounds may lead to acute chemical pneumonitis. Prolonged inhalation of low 

concentrations of less soluble forms are more often associated with chronic beryllium disease. Chronic 

beryllium disease may involve the induction of hyperplasia and hypertrophy of histiocytes (Policard 

1950). Mitogenic effects may be the result of interactions of beryllium ions with lymphocyte membranes 
BERYLLIUM 122 

3. HEALTH EFFECTS 

(Price and Skilleter 1985, 1986). Hypersensitivity may be due to the formation of a beryllium-protein 

complex that is antigenic. Beryllium stimulates a population of CD4+ T cells, and this reaction can be 

blocked by antibodies to HLA Class II molecules and by antibodies to the IL-2 receptor (Saltini et al. 

1989). In some cases, the manifestations of chronic beryllium disease may be reversed by corticosteroid 

therapy (Aronchick et al. 1987; Finkel 1983; Hardy and Stoeckle 1959). Although corticosteroids are 

used to control the clinical manifestations of chronic beryllium disease and to prevent further progression 

of the disease, steroid therapy is not without its own risks. 

Ingested soluble beryllium compounds may interact with phosphate to form insoluble beryllium 

phosphate particles that are sequestered in Kupffer cells of the liver (Tepper 1972). Diffusion of 

beryllium from the deposited particulates may cause damage to these cells and necrosis of the liver. 

Beryllium may also be taken up by lysosomes and cause release of lysomal enzymes, and beryllium may 

interfere with DNA synthesis in the nucleus. 

It has been established that beryllium inhibits DNA synthesis (Witschi 1968, 1970). Magnesium failed to 

influence the inhibitory effect of beryllium, although it had been shown that magnesium partly neutralizes 

the toxic effects of beryllium on fibroblasts or yeast cells (Lieben et al. 1964; Wainer 1972). 

Because of the variety of effects noted for beryllium and possible mechanisms of action for those effects, 

it is difficult to speculate regarding therapies that will interfere with specific mechanisms of action such 

that net toxic effects are reduced. Given the variety of effects possible for absorbed beryllium, the most 

effective strategy for reducing toxic effects may be to reduce the amount of free beryllium ion through 

sequestering or complexing reactions as discussed in Section 3.11.2. 

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 beryllium 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 beryllium. 
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3. HEALTH EFFECTS 

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 Beryllium 

The existing data on health effects of inhalation, oral, and dermal exposure of humans and animals to 

beryllium are summarized in Figure 3-5. The purpose of this figure is to illustrate the existing 

information concerning the health effects of beryllium. 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. 

Studies regarding adverse health effects in humans after exposure to beryllium or its compounds are 

limited (Figure 3-5). No studies were located regarding neurological, developmental, reproductive, or 

genotoxic effects in humans following inhalation exposure to beryllium or its compounds. Studies 

regarding death were limited to chronic inhalation exposure. An accidental leakage of beryllium did not 

cause respiratory, hepatic, or immunological effects. Most of the human data concerns respiratory effects 
BERYLLIUM 124 

3. HEALTH EFFECTS 

Figure 3-5. Existing Information on Health Effects of Beryllium 
 

BERYLLIUM 125 

3. HEALTH EFFECTS 

and lung cancer as a result of occupational exposure to beryllium or its compounds. Immunological data 

indicate that beryllium induces a T-cell lymphocyte-mediated immune response in the lung and skin. No 

studies were located regarding any effects in humans following oral exposure to beryllium. Since 

beryllium is poorly absorbed through the gastrointestinal wall, effects from this route of exposure are 

unlikely. For dermal exposure, only skin effects (ulcerations) were reported. 

The database for animals is more complete. LC50 values have been reported for a number of beryllium 

compounds. Systemic effects of acute, intermediate, and chronic exposure via inhalation include 

respiratory, cardiovascular, gastrointestinal, hematological, musculoskeletal, hepatic, renal, and dermal/ 

ocular effects. Immunological and carcinogenic effects were observed in various species after inhalation 

exposure to beryllium. No studies were located regarding neurological, developmental, reproductive, or 

genotoxic effects in animals after inhalation exposure to beryllium or its compounds. Oral LD50 values 

were reported for many of the beryllium compounds. No other oral exposure studies were located 

regarding acute effects in animals exposed to beryllium or its compounds. Immunological, neurological, 

reproductive, genotoxic, and carcinogenic effects due to ingestion of beryllium are reported in the 

available literature. 

No dermal studies were located regarding death, neurological, developmental, reproductive, genotoxic, or 

carcinogenic effects in animals. Acute dermal studies report dermatological effects of beryllium on 

sensitized animals. Since beryllium is a T-cell activator, exposure can cause immunological effects on the 

skin. 

3.12.2 Identification of Data Needs 

Acute-Duration Exposure. The lung is the main target organ of inhaled beryllium and its 

compounds in humans (Eisenbud et al. 1948a; Van Ordstrand et al. 1945) and animals (Haley et al. 1989; 

Hart et al. 1984; Robinson et al. 1968; Sanders et al. 1975; Schepers 1964; Sendebach and Witschi 1987b; 

Sendebach et al. 1980, 1989); however, the heart, liver, kidney, adrenal (Schepers 1965), skin (Stiefel et 

al. 1980), and the hematopoietic tissue (Hall et al. 1950) in animals have also been identified as target 

organs of beryllium exposure. The effects of occupational exposure to beryllium or its compounds 

include acute pneumonitis as a result of inhalation exposure to more soluble beryllium compounds or 

chronic beryllium disease as a result of inhalation of soluble and less soluble beryllium compounds (e.g., 

beryllium oxide) (Cullen et al. 1987; Eisenbud and Lisson 1983; Eisenbud et al. 1948a; Rossman et al. 

1988). Because an animal model that mimics all aspects of chronic beryllium disease has not been 
 

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3. HEALTH EFFECTS 

identified, it is inappropriate to use animal data to derive an acute-duration inhalation MRL. No human 

acute-duration studies were identified; thus, an acute-duration inhalation MRL was not identified. No 

data were located regarding effects in humans after acute oral exposure to beryllium. No acute oral MRL 

can be derived because the only acute oral data in animals involves lethality (Ashby et al. 1990; 

Kimmerie 1966; Lanchow University 1978; Venugopal and Luckey 1977). The target organs of acute 

oral exposure of animals to low levels of beryllium are not known, but beryllium compounds are poorly 

absorbed from the gastrointestinal tract (Furchner et al. 1973; Le Fevre and Joel 1986; Morgareidge et al. 

1975; Reeves 1965). In humans and animals sensitized to beryllium, contact with beryllium and its 

soluble and insoluble compounds can cause dermatitis and skin granulomas (Belman 1969; Curtis 1951; 

Marx and Burrell 1973; Williams et al. 1987). In general, the more soluble the compound the greater the 

sensitizing potential. Dermal effects usually occur on abraded skin. Dermal absorption of beryllium is 

assumed to be poor and would not likely cause further systemic effects. Dermal studies would be helpful 

to determine the amount and duration of exposure necessary for human sensitization. Additional human 

exposure studies that examine the potential of beryllium to cause beryllium sensitization and chronic 

beryllium disease after a <2 weeks of exposure would be useful for establishing an acute-duration 

inhalation MRL. The information regarding beryllium toxicity is useful to the general population and to 

populations residing at or near hazardous waste sites, who might be subject to acute exposure. 

Intermediate-Duration Exposure. No studies were located regarding effects in humans after 

intermediate-duration inhalation exposure to beryllium or its compounds. The available occupational 

exposure studies provide sufficient evidence that beryllium sensitization and chronic beryllium disease 

would be the most sensitive end points following intermediate-duration inhalation exposure to beryllium; 

however, no intermediate-duration studies were identified. Several studies indicate that the lung is the 

main target organ in animals for intermediate exposure to soluble and insoluble beryllium compounds via 

inhalation (Hall et al. 1950; Schepers 1964; Schepers et al. 1957; Stokinger et al. 1950; Wagner et al. 

1969). Other target organs in animals include the heart, liver, kidney, skin, and hematopoietic tissue (Hall 

et al. 1950; Stiefel et al. 1980; Stokinger et al. 1950). Derivation of an intermediate-duration inhalation 

MRL is precluded because there are no human intermediate-duration studies and an animal model that 

mimics all aspects of chronic beryllium disease has not been identified, thus making it inappropriate to 

derive an MRL from animal data. There are limited data on the toxicity of ingested beryllium following 

intermediate-duration exposure. The available animal data suggest that rickets is a critical end point 

following ingestion of beryllium carbonate (Guyatt et al. 1933; Jacobson 1933; Kay and Skill 1934). The 

rickets do not appear to be due to a direct effect of beryllium on the bone. Rather, the rickets are due to a 

phosphorus deficiency, which results from the binding of beryllium to dietary phosphorus in the gut. 
 

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Thus, the available data are insufficient for derivation of an intermediate-duration oral MRL. Additional 

studies involving exposure to low concentrations of several beryllium compounds would be useful for 

identifying critical targets of toxicity and establishing dose-response relationships. According to one 

study, guinea pigs were sensitized to beryllium via intradermal administration of beryllium compounds, 

with the sensitizing potential increasing with increasing solubility (Marx and Burrell 1973). 

Chronic-Duration Exposure and Cancer. Health effects in humans and animals after chronic 

exposure to beryllium and its compounds are reported in the available literature. The lung is the main 

target organ in human (Andrews et al. 1969; Cullen et al. 1987; Eisenbud and Lisson 1983; Hardy and 

Tabershaw 1946; Kreiss et al. 1993a, 1996, 1997; Rossman et al. 1988; Stange et al. 1996b) and animals 

(Reeves et al. 1967; Vorwald and Reeves 1959; Wagner et al. 1969) after inhalation exposure to 

beryllium and its compounds. Occupational exposure to soluble and insoluble beryllium compounds 

caused delayed granulomatous disease of the lung, known as chronic beryllium disease or berylliosis 

(Cotes et al. 1983; Cullen et al. 1987; Eisenbud and Lisson 1983; Eisenbud et al. 1949; Kreiss et al. 

1993a, 1996, 1997; Stange et al. 1996b). Acute lung inflammation was also observed after occupational 

exposure to soluble beryllium compounds (Eisenbud et al. 1948a). These serious respiratory effects in 

humans were found even at the lowest occupational exposure concentrations, which were lower than 

concentrations used in chronic inhalation experiments in animals. Therefore, NOAELs for respiratory 

effects due to occupational exposure or chronic inhalation exposure in animals have not been determined. 

An environmental exposure study did identify a NOAEL for chronic beryllium disease (Eisenbud et al. 

1949); however, technology available at the time of the study did not allow for the detection of beryllium 

sensitization or subclinical chronic beryllium disease and it is not known if the identified NOAEL would 

be protective for these effects. Hence, derivation of a chronic inhalation MRL is precluded. Data were 

not located regarding effects in humans after chronic oral exposure to beryllium. The results of a chronic 

dog study suggests that the gastrointestinal tract is a target of beryllium sulfate toxicity (Morgareidge et 

al. 1976). This study is the basis for a chronic-duration oral MRL for beryllium. The MRL was derived 

using a benchmark dose approach and the dose-response data for small intestinal lesions in dogs 

(Morgareidge et al. 1976). Data regarding the effects of chronic dermal exposure to beryllium were 

limited to findings of dermatitis in occupationally exposed individuals (Curtis 1951; Van Ordstrand et al. 

1946; Williams et al. 1987). Studies regarding inhalation and dermal exposure to low concentrations of 

beryllium for chronic durations would be useful for determining the respective NOAELs for respiratory 

and dermal effects. Studies in dogs exposed to beryllium oxide by inhalation (Finch et al. 1990) and in 

guinea pigs (Barna et al. 1981, 1984) and in mice (Huang et al. 1992) exposed to beryllium oxide 

intratracheally have been performed to identify an appropriate model to elucidate the pathogenesis of 
 

BERYLLIUM 128 

3. HEALTH EFFECTS 

chronic beryllium disease in humans. However, an animal model that exactly mimics chronic beryllium 

disease in humans has not been found. Further inhalation studies conducted in several species of animals 

designed to identify the most appropriate animal model that mimics chronic beryllium disease in humans 

would be useful to for determining mechanisms for induction and treatment of chronic beryllium disease. 

This work is in progress (see Section 3.12.3). This information would be useful to the general population 

and to populations residing at or near hazardous waste sites. 

Data regarding occupational exposure to beryllium and its compounds appear to indicate an increased 

incidence of lung cancer (Infante et al. 1980; Mancuso 1970, 1979, 1980; Sanderson et al. 2001a; 

Steenland and Ward 1992; Wagoner et al. 1980; Ward et al. 1992). However, the quality of some of these 

studies has been severely criticized (EPA 1987). Animal studies indicate increases in lung cancer due to 

inhalation exposure to beryllium or its soluble and insoluble compounds (Nickell-Brady et al. 1994; 

Reeves et al. 1967; Vorwald 1968; Vorwald and Reeves 1959; Wagner et al. 1969), but these studies are 

also flawed. Nevertheless, these data and studies conducted by intratracheal, intravenous, and 

intramedullary routes taken as a whole support the carcinogenic potential of beryllium, and inhaled 

beryllium is considered a human carcinogen (IARC 2001; NTP1999, 2002); EPA considers beryllium to 

be a probable human carcinogen (IRIS 2002). A well-conducted chronic inhalation study in rats and mice 

using several exposure levels would add confidence to the database and eliminate uncertainties due to the 

flaws in the existing studies. Beryllium has not been found to cause cancer in animals after oral exposure 

(Morgareidge et al. 1975, 1976; Schroeder and Mitchener 1975a, 1975b); although, as previously noted, 

these studies may not have been adequate to assess carcinogenic potential. Beryllium and its compounds 

are poorly absorbed from the gastrointestinal tract. Therefore, conducting oral studies at doses high 

enough to affect plausible target organs would be difficult. 

Genotoxicity. Genotoxicity data regarding exposure to beryllium or its compounds are contradictory. 

Forward and reverse mutation bacterial assays yielded both positive (Kanematsu et al. 1980; Ulitzur and 

Barak 1988) and negative (Arlauskas et al. 1985; Ashby et al. 1990; Rosenkranz and Poirier 1979; 

Simmon et al. 1979) results for the same compounds. The results are also contradictory for chromosomal 

aberrations induced by beryllium in mammalian cell cultures (Ashby et al. 1990; Brooks et al. 1989; Hsie 

et al. 1979; Larramendy et al. 1981; Miyaki et al. 1979; Williams et al. 1989). Studies to examine the 

mechanism of mutagenic activity of beryllium would be useful. Studies regarding the genotoxic potential 

of beryllium in occupationally exposed workers also would be useful, especially if exposure levels were 

related to genotoxic effects. In addition, studies regarding the in vivo genotoxic potential of beryllium in 

animals, particularly by the inhalation route, would be helpful. 
 

 

 

BERYLLIUM 129 

3. HEALTH EFFECTS 

Reproductive Toxicity. No studies were located regarding reproductive toxicity in humans after 

inhalation, oral, or dermal exposure to beryllium or its compounds. A chronic duration study that allowed 

continuous mating did not find any adverse reproductive effects in dogs exposed to beryllium sulfate in 

the diet (Morgareidge et al. 1976). A study involving histological examination of rats exposed to 

beryllium sulfate in drinking water for 2 years reported no alterations of the reproductive organs 

(Morgareidge et al. 1975); beryllium compounds are not well absorbed by the gastrointestinal tract. 

Another study involving intratracheal injection of beryllium oxide in rats reported no effects on 

reproductive function (Clary et al. 1975). Additional inhalation studies should examine reproductive 

organs in order to determine whether the potential for reproductive effects due to beryllium exposure 

exists. 

Developmental Toxicity. No studies were located regarding developmental toxicity in humans after 

inhalation, oral, or dermal exposure to beryllium or its compounds. No developmental effects were 

observed in the offspring of dogs chronically exposed to beryllium sulfate in the diet (Morgareidge et al. 

1976); although the usefulness of this study in establishing the potential developmental toxicity of 

ingested beryllium is limited by the nonconventional study design. No inhalation or dermal exposure 

studies examining developmental toxicity in animals were identified. Rats injected intravenously with 

beryllium nitrate during gestation delivered pups that died soon after birth (Mathur et al. 1987). Increased 

fetal mortality and fetal weight and increased abnormalities were observed after pregnant rats were 

injected intratracheally with beryllium oxide or beryllium chloride (Selivanova and Savinova 1986). 

Other studies in which beryllium salts were injected into pregnant mice indicated that beryllium can 

penetrate the placenta and reach the fetus and cause behavioral abnormalities in the offspring (Bencko et 

al. 1979; Tsujii and Hoshishima 1979). Additional animal studies would be useful to determine if 

developmental effects may occur after inhalation or oral exposure to beryllium. 

Immunotoxicity. While beryllium has not been shown to be toxic to the immune system, beryllium 

and the soluble and insoluble compounds can be sensitizing and induce a cell-mediated immune response 

to beryllium (Cullen et al. 1987; Johnson 1983; Rossman et al. 1988; Saltini et al. 1989). This heightened 

immune response to beryllium is the cause of chronic beryllium disease and certain skin lesions (Williams 

et al. 1987). Granuloma formation and dermatitis are the principal immunological effects caused by 

exposure to beryllium. Although beryllium is not well absorbed by the gastrointestinal tract, studies 

evaluating the immunological effects of beryllium exposure to the associated lymphoid tissue would be 

useful to determine the local immunological reaction. Intermediate-duration studies designed to 

characterize the effects on the immune system would be helpful. The elucidation of the molecular 
 

 

 

BERYLLIUM 130 

3. HEALTH EFFECTS 

mechanisms of the immune response to beryllium and the identification of the specific T-cell families that 

are reactive to beryllium would aid in the identification and treatment of patients with chronic beryllium 

disease. In addition, identification of potential differences in allelic phenotypes between people with 

chronic beryllium and people exposed to beryllium but without chronic beryllium disease might help 

identify potentially susceptible populations based on genetic differences. 

Neurotoxicity. No studies were located regarding neurotoxicity in humans after inhalation, oral, or 

dermal exposure to beryllium or its compounds. Histological examination of rats and dogs chronically 

exposed to beryllium sulfate in drinking water did not reveal any abnormalities in nerve tissues 

(Morgareidge et al. 1975, 1976). Beryllium is not well absorbed by the gastrointestinal tract or after 

dermal exposure; therefore, neurological effects are not expected to occur as a result of oral or dermal 

exposure. Inhalation studies involving low-level exposure to beryllium would be useful for determining 

its neurotoxicity. 

Epidemiological and Human Dosimetry Studies. The general population is exposed to 

beryllium through contaminated air, water, and food. The highest exposure levels are incurred by 

workers in beryllium ore processing, manufacturing, or fabricating plants (Eisenbud and Lisson 1983). 

Few studies correlate beryllium exposure with effects on the respiratory system. Epidemiology data have 

been criticized for using inappropriate cohorts and including nonexposed workers. Studies that correlate 

occupational exposure to beryllium with cancer and other health effects would be useful and would offset 

the limitations of the now available studies. 

Biomarkers of Exposure and Effect. There are several tests for detecting beryllium in biological 

fluids and tissues (Frame and Ford 1974; Foreman et al. 1970; Hurlburt 1978; IARC 1980; Martinsen and 

Thomassen 1986; Paschal and Bailey 1986; Shan et al. 1989). Increased levels of beryllium in urine and 

blood indicate exposure (Stiefel et al. 1980; Zorn et al. 1986). Beryllium has also been measured in 

granulomas in the lung tissue of individuals with chronic beryllium disease (Kanarek et al. 1973) and in 

the skin of beryllium sensitive individuals (Williams et al. 1987). Laser ion mass analysis for beryllium is 

the most sensitive test for identifying beryllium on histological sections from lung or skin granulomas of 

patients with chronic beryllium disease (Williams and Kelland 1986). A lymphocyte proliferation test has 

also been used to identify workers with chronic beryllium disease; positive test results rarely occur in 

workers who are not exposed to beryllium or its compounds (James and Williams 1985; Stokes and 

Rossman 1991). 
 

BERYLLIUM 131 

3. HEALTH EFFECTS 

Chronic exposure to beryllium can result in decreased lung function (Andrews et al. 1969; Johnson 1983). 

This decrease can be measured by spirometry such as forced expiratory volume in 1 second or forced vital 

capacity (Andrews et al. 1969; Kriebel et al. 1988a,b). Measurements of lung function cannot distinguish 

between chronic beryllium disease and sarcoidosis, and lung opacities are not definitively captured by 

x-rays (Kanarek et al. 1973). Lymphocyte proliferation assays on cells obtained from individuals by 

bronchoalveolar lavage are sensitive in confirming chronic beryllium disease in symptomatic individuals 

(James and Williams 1985; Rossman et al. 1988). The lymphocyte proliferation test also distinguishes 

between chronic beryllium disease and sarcoidosis. A less invasive method of determining sensitivity to 

beryllium would be useful, especially for monitoring health effects in individuals living at or near 

hazardous waste sites. 

Absorption, Distribution, Metabolism, and Excretion. Beryllium and its compounds are 

absorbed primarily through the lungs in humans and animals (Finch et al. 1990; Reeves and Vorwald 

1969; Stiefel et al. 1980; Zorn et al. 1986), but the available information is not sufficient to determine the 

rate and extent of pulmonary absorption. Soluble compounds are absorbed more readily than insoluble 

compounds (Finch et al. 1990). Information from animal studies indicates that beryllium is poorly 

absorbed from the gastrointestinal tract, with the majority of the dose excreted in the feces (Furchner et al. 

1973; Le Fevre and Joel 1986; Morgareidge et al. 1975; Reeves 1965). Dermal absorption is also poor 

(Petzow and Zorn 1974). Studies regarding the rate and extent of beryllium absorption via the lungs 

would be useful. 

The only study on the distribution of beryllium and its compounds in humans was conducted on tissue 

taken from autopsies (Meehan and Smythe 1967); distribution studies in animals exposed to beryllium via 

inhalation were more available (Finch et al. 1990; Rhoads and Sanders 1985; Sanders et al. 1975; Stiefel 

et al. 1980; Stokinger et al. 1950; Wagner et al. 1969; Zorn et al. 1977). The target organs identified in 

these studies were the lung, lymph nodes, kidney, liver, and bone. Distribution of beryllium is more 

widespread for the soluble compounds, reflecting the degree of absorption (Finch et al. 1990). Rats and 

guinea pigs achieved steady state concentrations in the lungs 36 weeks after initial exposure to beryllium 

sulfate (Reeves and Vorwald 1969). Steady state concentrations in the blood were reached after 

8–12 hours (Stiefel et al. 1980). After oral exposure to beryllium metal, beryllium sulfate, or beryllium 

oxide, beryllium was distributed primarily to the liver and then to the kidneys, lymph nodes, blood, and 

bone (Le Fevre and Joel 1986; Morgareidge et al. 1975; Reeves 1965; Watanabe et al. 1985). Studies 

investigating distribution patterns of dermally absorbed beryllium would be useful to determine if 

sensitization to beryllium can occur after dermal exposure. 
 

 

BERYLLIUM 132 

3. HEALTH EFFECTS 

Beryllium is not biotransformed in the body. Studies involving the conversion of soluble beryllium 

compounds to insoluble compounds would be useful to determine the residence time of the compounds in 

the gastrointestinal tract. Studies investigating the binding of beryllium to proteins or nucleic acids would 

be useful in determining the antigenic forms of beryllium, as well as a possible mechanism for 

genotoxicity. 

Information regarding the clearance of beryllium from serum in humans (Stiefel et al. 1980; Zorn et al. 

1986) and animals (Finch et al. 1990; Rhoads and Sanders 1985; Sanders et al. 1975; Stiefel et al. 1980; 

Zorn et al. 1977) after inhalation exposure to beryllium compounds is reported in the available literature. 

Beryllium compounds are poorly absorbed by the gastrointestinal tract, and primarily eliminated in the 

feces (Furchner et al. 1973; Morgareidge et al. 1975; Reeves 1965). Studies regarding excretion after 

dermal exposure to beryllium and its compounds were not located in the available literature. 

Comparative Toxicokinetics. Studies in cats, rats, monkeys, and dogs indicate quantitative and 

qualitative differences in the distribution of inhaled beryllium to the lung, bone, spleen, and lymph nodes 

(Finch et al. 1990; Rhoads and Sanders 1985; Sanders et al. 1975; Stiefel et al. 1980; Stokinger et al. 

1950; Wagner et al. 1969; Zorn et al. 1977). No studies were located comparing the differences in 

inhalation exposures among species with respect to absorption or excretion. Since beryllium is not well 

absorbed by the gastrointestinal tract or after dermal exposure, comparative studies for these routes of 

exposure would not be particularly valuable. Additional comparative toxicokinetics studies regarding 

distribution, absorption, and excretion of inhaled beryllium would be helpful to determine the use of the 

appropriate animal model to study acute and chronic beryllium disease. 

Methods for Reducing Toxic Effects. Beryllium is poorly absorbed after oral and dermal 

exposure, obviating the need to develop methods to reduce absorption following these routes. While 

beryllium is absorbed by the lungs, the major effects of inhalation exposure to beryllium are acute 

chemical pneumonitis, which is associated with soluble beryllium compounds and chronic berylliosis, 

which is associated with retention of unabsorbed less soluble beryllium compounds in the lungs (Finch et 

al. 1990). Testing of bronchoalveolar lavage to enhance beryllium clearance from the lungs might 

prevent or reduce the severity of berylliosis. The chelating agent, aurine tricarboxylic acid, by combining 

with beryllium ions, increases the urinary excretion of beryllium in animals (Venugopal and Luckey 

1978). However, metal chelating agents available for use in human clinical medicine have not been 

shown to be effective in reducing the toxicity of beryllium (Hall and Rumack 1992). Effects of soluble 

beryllium compounds (liver necrosis due to sequestration of insoluble beryllium phosphate formed from 
 

BERYLLIUM 133 

3. HEALTH EFFECTS 

the interaction with phosphate, acute pneumonitis, immunological effects) are probably due to beryllium 

ions (Price and Skilleter 1985, 1986). Further studies on the influence of chelating agents on berylliuminduced effects would aid in establishing effective strategies for preventing or reducing the severity of 

these effects. Absorbed beryllium appears to preferentially accumulate in bone, and beryllium may 

substitute for calcium in bone, resulting in rickets or osteoporosis (Guyatt et al. 1933; Jacobson 1933). 

Studies could be performed to determine whether a high calcium diet would be effective in preventing the 

replacement of calcium by beryllium in bone. 

Children’s Susceptibility. No information on the toxicity of beryllium in children has been located. 

Studies that examine sensitive end points such as the lung, immune, and gastrointestinal effects in young 

animals would be useful for assessing whether children will be unusually susceptible to beryllium 

toxicity. The available animal data are inconclusive to determine whether the developing organism is 

sensitive to beryllium toxicity. As discussed in Chapter 2 and in Section 3.2.2.6, the only available oral 

study did not find developmental effects in the offspring of dogs chronically exposed to beryllium sulfate 

in the diet (Morgareidge et al. 1976). However, injection studies have found developmental effects (fetal/ 

neonatal mortality, internal abnormalities, and behavioral effects) (Bencko et al. 1979; Mathur et al. 1987; 

Selivanova and Savinova 1986; Tsujii and Hoshishima 1979). Data needs relating to development are 

discussed in detail in the Developmental Toxicity subsection above. There are some data to suggest that 

beryllium can cross the placenta and be transferred to an infant via breast milk (Krachler et al. 1999a). 

The available toxicokinetic data did not evaluate the potential differences between adults and children. 

Toxicokinetic studies examining how aging can influence the absorption, distribution, and excretion of 

beryllium would be useful in assessing children’s susceptibility to beryllium toxicity. There are no data 

to determine whether there are age-specific biomarkers of exposure or effects or any interactions with 

other chemicals that would be specific for children. Research in adults on methods for reducing 

beryllium toxic effects or body burdens would also be applicable to children. 

Child health data needs relating to exposure are discussed in 6.8.1 Identification of Data Needs: 

Exposures of Children. 
BERYLLIUM 134 

3. HEALTH EFFECTS 

3.12.3 Ongoing Studies 

Ongoing studies pertaining to beryllium have been identified and are shown in Table 3-6. 
BERYLLIUM 135 

3. HEALTH EFFECTS 

Table 3-6. Ongoing Studies on Beryllium 

Investigator Affiliation Research description Sponsor 

Albertini, RJ University of Vermont Biomarkers for beryllium sensitization EM 

Marian, B University of California, Screening of beryllium worker cohorts NCR 

Los Alamos National using the immun.-flow lymphocyte 

Laboratory proliferation test 

Newman, L University of Colorado Immunopathogenesis of beryllium NCR 

disease 

Rossman, M University of Pennsylvania Examination of exposure-response NCR 

relationship for various measures of 

beryllium exposure 

Kotzin, BL University of Colorado Examination of T–cell clones in NHLBI 

individuals with CBD and beryllium 

sensitized individuals 

King, TE National Jewish Medical Prevention of pulmonary fibrosis in NHLBI 

and Research Center individuals with granulomatous 

inflammation 

Newman, L National Jewish Medical Role of T–cells and mast cells in the NHLBI 

and Research Center development of pulmonary fibrosis 

Mason, RJ National Jewish Medical Immunologic regulation of pulmonary NHLBI 

and Research Center fibrosis 

Warren, JS University of Michigan Study of oxidant-induced β-chemokines NHLBI 

in granuloma formation 

Fontenot, AP University of Colorado Pathogenic cells in beryllium-induced NHLBI 

lung disease 

LA Maier National Jewish Medical Local angiotensin system in lung NHLBI 

and Research Center fibrogenesis 

Bell, J Fayetteville State Mutagenic effects of beryllium on the NIGMS 

University fidelity of DNA synthesis 

Newman, L National Jewish Medical Cytokine regulation in CBD NIEHS 

and Research Center 

Finch, GL Lovelace Biomedical and Mechanisms of granulomatous disease USDOE 

Environmental Research from inhaled beryllium 

Institute 

CBD = chronic beryllium disease; NCR = National Center for Research Resources; NHLBI = National Heart, Lung, 

and Blood Institute; NIEHS = National Institute of Environmental Health and Science; NIGMS = National Institute of 

General Medical Sciences; USDOE = U.S. Department of Energy 

BERYLLIUM 137 

4. CHEMICAL AND PHYSICAL INFORMATION 

4.1 CHEMICAL IDENTITY 

Beryllium is a naturally occurring element found in earth’s surface rocks at levels of 1–15 mg/kg. It 

appears in Group IIA of the periodic table and has two common oxidation states, Be(0) and Be(+2). 

Because of its high reactivity, beryllium is not found as the free metal in nature. There are approximately 

45 mineralized forms of beryllium. The important beryllium minerals in the world are beryl 

(3BeO#Al2O3#6SiO2) and bertrandite (Be4Si2O7(OH)2). Beryl has been known since ancient times as the 

gemstones: emerald (green), aquamarine (light blue), and beryl (yellow). Information concerning the 

chemical identity of elemental beryllium and beryllium compounds is listed in Table 4-1. 

4.2 PHYSICAL AND CHEMICAL PROPERTIES 

The physical and chemical properties of beryllium and beryllium compounds are listed in Table 4-2. 

Consistent with the high charge-to-radius ratio, beryllium has a strong tendency to form compounds with 

covalent bonds; even compounds with the most electronegative elements (e.g., BeF2) have substantial 

covalent character. Although beryllium belongs to Group IIA of the periodic table, it is chemically very 

similar to aluminum, which also has a high charge-to-radius ratio. Like aluminum, the hydroxide of 

beryllium is amphoteric (Cotton and Wilkinson 1980; Drury et al. 1978; EPA 1998). 

The interaction of cosmic-ray particles in the atmosphere produces a number of radionuclides including 

beryllium-7 (Be-7) and beryllium-10 (Be-10). The radioactive half-life of Be-7 is 53.29 days and the 

radioactive half-life of Be-10 is 1.51x106

 years (UNSCEAR 2000). 
Table 4-1. Chemical Identity of Beryllium and Beryllium Compoundsa 

Characteristic Synonym(s) Registered trade name(s) Chemical formula Identification numbers: 

Beryllium 

Beryllium-9; 

glucinium; glucinum; beryllium metallic 

No data 

Be 

Beryllium chloride 

Beryllium dichloride 

No data 

BeCl2 

Beryllium fluoride Beryllium hydroxide 

Beryllium difluoride Beryllium hydrate; 

beryllium dihydroxide 

No data No data 

BeF2 Be(OH2) 

CAS registry 7440-41-7 7787-47-5 7787-49-7 13327-32-7 NIOSH RTECS DS1750000 DS2625000 DS2800000 DS3150000 EPA hazardous waste P015 b No data No data No data 

OHM/TADS 72116604c 7217359c 7800049c No data 

DOT/UN/NA/IMCO shipping UN1567/IM06.1 NA1566/IM06.1 NA1566/IM06.1 UN1566/IM06.1 HSDB 512 357 355 350 NCI No data No data No data No data 
Table 4-1. Chemical Identity of Beryllium and Beryllium Compoundsa (continue

Characteristic 

Beryllium phosphate (3H2O) Beryllium nitrate Beryllium sulfate 

Synonym(s) Beryllium 

orthophosphated 

Nitric acid, beryllium salt 

Sulfuric acid, beryllium salt 

Registered trade name(s) No data No data No data 

Chemical formula Be3(PO4)2 -3

H2Od Be(NO3)2 BeSO4 

Identification numbers: 

CAS registry NIOSH RTECS 

35089-00-0d 

No data 

13597-99-4 (anhydrous) 13510-48-0 (tetrahydrate) DS3675000 

13510-49-1 (anhydrous) 14215-00-0 (2H2O) 

7787-56-6 (4H2O) 

DS48000000 

EPA hazardous waste No data 

(anhydrous) No data 

(anhydrous) No data 

OHM/TADS DOT/UN/NA/IMCO shipping HSDB 

No data No data No data 

7217227c 

(anhydrous) UN2464/IM05.1 1431 

7217228c 

(anhydrous) UN1566/IM06.1 347 

NCI No data No data No data 

aAll information obtained from HSDB 2000 except where noted bEPA Hazardous waste list P015 applies to beryllium powder only cOHM/TADS 1990dWeast 1985 eIARC 1980 

CAS = Chemical Abstracts Services; DOT/UN/NA/IMCO = Department of Transportation/United Nations/North America/International MaCode; EPA = Environmental Protection Agency; HSDB = Hazardous Substances Data Bank; NCI = National Cancer Institute; NIOSH = 

Occupational Safety and Health; OHM/TADS = Oil and Hazardous Materials/Technical Assistance Data System; RTECS = Registry of TSubstances 
Table 4-2. Physical and Chemical Properties of Beryllium and Beryllium Compou

Property Molecular weight 

Beryllium metal 

9.012 

Beryllium fluoride 

47.01 

Beryllium hydroxide 

43.03b 

Beryllium oxide 

25.01 

B(

1

Color Gray Colorless Whitec White W

Physical state Melting point 

Solid; hexagonal 

structured 

1,287–1,292 ECe 

Glassy, hygroscopic massd 555 ECb 

Amorphous powder or crystalline solidd Decomposes (loses water) when heatedf 

Light, amorphous powderd 2,508–2,547 ECb 

PN

Boiling point Density 

2,970 ECe 

1.846 g/cm3 e 

1,175 ECb 1.986 g/cm3 (25 EC)b 

Not applicable 1.92 g/cm3 b 

3,787 ECb 

3.016 g/cm3 c 

NN

Odor None None None None N

Odor threshold: Not applicable Not applicable Not applicable Not applicable NSolubility: 

Water Other solvent(s) 

Insolubleg 

Soluble in dilute acid and alkali 

Very solubleg Slightly soluble in alcohold 

0.8x10-4 mol/Lg (3.44 mg/L) Soluble in hot concentrated acid and alkalid 

Very sparinglyg Soluble in concentrated acidsd 

IndS

Partition coefficients: 

Log Kow 

Log Koc 

No data No data 

No data No data 

No data No data 

No data No data 

NN

Vapor pressure 1 mmHg (1,520 EC) No data No data No data N

Henry’s law constant No data No data No data No data N

Autoignition temperature No data No data No data No data N

Flashpoint No data No data No data No data N

Flammability limits Conversion factorsh 

No data No data No data No data N

Explosive limits No data No data No data No data N
Table 4-2. Physical and Chemical Properties of Beryllium and Beryllium Compoundsa (

Property Molecular weight 

Beryllium chloride 

79.92 

Beryllium nitrate (tetrahydrate) 

205.08b 

Beryllium phosphate (trihydrate) 

271.03 

Beryllium sulfate 

105.07 

B(

1

Color Colorless Whiteb Whiteb Colorlessb C

Physical state Needles Crystalsb Solidb Tetragonal crystals T

Melting point 405 EC 60.5 ECb 100 EC (loses H2O) 

(decomposes)b 

550–600 EC (decomposes) 

1

Boiling point 520 EC 142 EC (decomposes)b No data Not applicable 4Density 1.899 g/cm3 (25 EC) 1.557 g/cm3 b No data 2.443 g/cm3 1

Odor None Noneb Noneb None N

Odor threshold: Not applicable Not applicable Not applicable Not applicable NSolubility: 

Water Other solvent(s) 

Very soluble Very soluble in alcohol, ether, pyridine; slightly soluble in benzene and chloroform 

166 parts/100 parts H2O (20 EC)b (1.66x106 mg/L) 

No data 

Soluble Soluble in acetic acid 

Insoluble No data 

3H

(3

S

in

Partition coefficients: 

Log Kow 

Log Koc 

No data No data 

No data No data 

No data No data 

No data No data 

NN

Vapor pressure No data No data No data No data N

Henry’s law constant No data No data No data No data N

Autoignition temperature No data No data No data No data N

Flashpoint No data No data No data No data N
Table 4-2. Physical and Chemical Properties of Beryllium and Beryllium Compoundsa (

Property Beryllium chloride 

Beryllium nitrate (tetrahydrate) 

Beryllium phosphate (trihydrate) Beryllium sulfate 

B(

Flammability limits Conversion factors 

No data 

h 

No data 

h 

No data 

h 

No data 

h 

N

h 

Explosive limits No data No data No data No data NaAll information obtained from Weast 1985 except dWindholz 1983 hThese compounds do not 

where noted eBallance et al. 1978 the vapor phase; therefore

bDean 1985 fWalsh and Rees 1978 is not applicable. cHawley 1981 gEPA 1987 
BERYLLIUM 143 

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

5.1 PRODUCTION 

Beryllium is an element that is present in the earth’s surface rocks in amounts ranging from <1–15 mg/kg. 

The beryllium minerals of commercial interest are beryl (i.e., 3BeOCAl2O3C6SiO2) and bertrandite (i.e., 

Be4Si2O7(OH)2). In the United States, bertrandite, which contains <1% beryllium, is the principal mineral 

mined. Outside the United States, beryl is the principal beryllium mineral mined. In 1999, the U.S. 

Geological Survey (USGS) estimated that United States resources of bertrandite ore in Utah and Texas 

contained 21,000 metric tons of beryllium (Cunningham 1999). Only one company, Brush Wellman, Inc. 

of Elmore, Ohio, produced beryllium in the United States in 1998. The bertrandite ore was mined using 

open-pit methods from deposits near Spor Mountain, Utah. In 1998, 230 metric tons of beryllium were 

mined in the United States (Cunningham 1999). Beryllium hydroxide is the basic raw material for the 

production of beryllium metal, alloys, and compounds. Bertrandite ore is wet milled, leached with 

sulfuric acid, and then extracted from the acid leachate with di(2-diethylhexyl) phosphate in kerosene at 

elevated temperature. The beryllium is then treated with aqueous ammonium carbonate to form an 

aqueous ammonium beryllium carbonate complex, which is then heated to precipitate beryllium as 

carbonate. Continued heating liberates carbon dioxide and beryllium hydroxide (i.e., Be(OH)2). 

Beryllium hydroxide is then recovered by filtration. Beryllium hydroxide is the feed material for 

products such as beryllium metal, beryllium alloys, and beryllium oxide (Ballance et al. 1978; Drury et al. 

1978). 

Beryllium metal is produced by Brush Wellman Inc. in Elmore, Ohio using the Schenzfeier-Pomelee 

purification process. The hydroxide is initially reacted with ammonium fluoride to form ammonium 

fluoroberyllate (e.g., (NH4)2BeF4), which is then heated to produce an amorphous beryllium fluoride (e.g., 

BeF2), which is reduced by magnesium metal at 900–1,300 EC to yield beryllium metal and a beryllium 

fluoride-magnesium fluoride slag. The slag is removed by leaching with water, leaving 97% pure 

beryllium metal. Beryllium metal may be further electrorefined to produce a higher purity material 

(Ballance et al. 1978; Drury et al. 1978). Beryllium oxide (i.e., BeO) is the most important high purity 

commercial beryllium chemical. It is produced by dissolving technical-grade beryllium hydroxide in 

sulfuric acid, precipitating out hydrated beryllium sulfate, which is then calcined at 1,150–1,450 EC 

(Ballance et al. 1978; Drury et al. 1978). 
BERYLLIUM 144 

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

Copper-beryllium alloy is commercially the most important beryllium alloy. Copper-beryllium master 

alloy is manufactured by an arc-furnace method in which beryllium oxide is reduced by carbon in the 

presence of molten copper at 1,800–2,000 EC. The resulting master alloy usually contains 4.0–4.25% 

beryllium by weight. Other copper-beryllium alloys are produced by melting the master alloy together 

with virgin copper, copper scrap, and possibly other metals (Ballance et al. 1978; Drury et al. 1978). 

Brush Wellman, Inc. of Elmore, Ohio is the only processor of beryllium ores in the United States. Brush 

Wellman, Inc. is also the leading producer and consumer of beryllium metal, alloys, and oxide. NGK 

Metals Corporation in Reading, Pennsylvania is also a major U.S. manufacturer of beryllium alloys. U.S. 

mine shipments steadily increased from 173 metric tons in 1994 to 230 metric tons in 1998 of beryllium 

metal equivalent. Including imports of beryllium ore, stockpiling, and inventory uses, the apparrent U.S. 

consumption of beryllium from 1994 to 1998 has increased from 198 to 240 metric tons of beryllium 

equivalent (Cunningham 1999). Tables 5-1 and 5-2 list the number of facilities in each state that 

manufacture or process beryllium and beryllium compounds, respectively. Included in these tables are 

the activities and uses of beryllium and beryllium compounds and the range of maximum amounts of 

beryllium and beryllium compounds that are stored on site (TRI99 2002). 

5.2 IMPORT/EXPORT 

In 1998, 13% of the beryllium ore and metal consumed in the United States (35 metric tons) was imported 

from other countries. All imports of beryllium ore originated from Canada. Exports of beryllium metal 

were 60 metric tons in 1998, up from 29 metric tons in 1994. Japan, France, the United Kingdom, and 

Germany were the major recipients of beryllium exports during this period (Cunningham 1999). 

5.3 USE 

In 1998, the use of beryllium (as an alloy, metal, or oxide) in the electronic and electrical components, 

aerospace, and defense applications accounted for >80% of its consumption (Cunningham 1999). 

Beryllium metal is used in aircraft disc brakes, x-ray transmission windows, space vehicles optics and 

instruments, aircraft/satellite structures, missile guidance systems, nuclear reactor neutron reflectors, 

nuclear warhead triggering devices, fuel containers, precision instruments, rocket propellants, 
BERYLLIUM 145 

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

Table 5-1. Facilities that Produce, Process, or Use Beryllium 

Number of Minimum amount Maximum amount 

Statea facilities on site in poundsb on site in poundsb Activities and usesc 

CA 2 0 999 8, 10 

IN 2 100 999,999 9, 12 

LA 1 0 99 1, 5, 9, 13 

MO 1 1,000 9,999 8, 10 

NC 1 100,000 999,999 10, 13 

OH 1 10,000 99,999 1, 4 

OK 2 100 99,999 1, 5, 9 

PA 1 10,000 99,999 10 

SC 1 100 999 9 

UT 1 1,000 9,999 8 

WI 1 10,000 99,999 8 

Source: TRI99 2002 

a

Post office state abbreviations used 

b

Amounts on site reported by facilities in each state c

Activities/Uses: 

1. Produce 6. Impurity 10. Repackaging 

2. Import 7. Reactant 11. Chemical Processing Aid 

3. Onsite use/processing 8. Formulation Component 12. Manufacturing Aid 

4. Sale/Distribution 9. Article Component 13. Ancillary/Other Uses 

5. Byproduct 
BERYLLIUM 146 

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

Table 5-2. Facilities that Produce, Process, or Use Beryllium Compounds 

Number of Minimum amount Maximum amount 

Statea facilities on site in poundsb on site in poundsb Activities and usesc 

AL 4 1,000 99,999 1, 3, 4, 5, 6, 9, 1, 13 

AR 1 1,000 9,999 1, 5 

AZ 3 10,000 9,999,999 1, 3, 4, 5, 6, 9, 1 

FL 2 0 9,999 1, 3, 4, 5, 6, 1 

GA 3 10,000 99,999 1, 3, 4, 5, 6, 1, 13 

IL 1 1,000 9,999 1, 5, 1 

IN 3 100 99,999 1, 5, 6, 9, 1, 13 

KY 5 0 99,999 1, 2, 3, 5, 6, 9, 1, 13 

MI 2 10,000 99,999 1, 5, 9, 1 

MO 1 1,000 9,999 9 

MS 1 100 999 1, 5 

MT 1 10,000 99,999 1, 3, 5, 6, 13 

NC 2 10,000 99,999 1, 3, 4, 5, 6, 1 

NM 3 100 99,999 1, 3, 4, 5, 6, 1, 13 

NY 1 100 999 1, 5 

OH 4 1,000 99,999 1, 3, 4, 5, 6, 8, 1, 13 

PA 4 100 999,999 1, 2, 3, 4, 5, 6, 7, 9, 1 

TN 2 10,000 99,999 1, 5, 8, 9 

TX 1 10,000 99,999 1, 3, 4, 5, 6, 1, 13 

UT 4 1,000 49,999,999 1, 4, 7, 8, 13 

WI 1 1,000 9,999 9 

WV 3 1,000 99,999 1, 3, 4, 5, 6, 1, 13 

WY 1 0 99 1, 5, 6 

Source: TRI99 2002 

a

Post office state abbreviations used 

b

Amounts on site reported by facilities in each state c

Activities/Uses: 

1. Produce 6. Impurity 10. Repackaging 

2. Import 7. Reactant 11. Chemical Processing Aid 

3. Onsite use/processing 8. Formulation Component 12. Manufacturing Aid 

4. Sale/Distribution 9. Article Component 13. Ancillary/Other Uses 

5. Byproduct 
BERYLLIUM 147 

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

navigational systems, heat shields, mirrors, high speed computer, and audio components, as well as other 

uses (Ballance et al. 1978; Cunningham 1998). 

Beryllium oxide is used in high technology ceramics, electronic heat sinks, electrical insulators, 

microwave oven components, gyroscopes, military vehicle armor, rocket nozzles crucibles, thermocouple 

tubing, laser structural components, substrates for high-density electrical circuits, automotive ignition 

systems, and radar electronic countermeasure systems (Ballance et al. 1978, Cunningham 1998). 

Beryllium-copper alloys are used in a wide variety of applications because of their electrical and thermal 

conductivity, high strength and hardness, good corrosion and fatigue resistance, and nonmagnetic 

properties. Beryllium-copper alloys are manufactured into: springs; electrical connectors and relays; 

precision instruments; bushings and bearings in aircraft and heavy machinery; nonsparking tools; 

submarine cable housing and pivots; wheels and pinions; switches in automobiles; molds for injection 

molded plastics; radar; telecommunications; factory automation; computers; home appliances; 

instrumentation and control systems; tubing in oil and drilling equipment; connectors for fiber optics; and 

integrated circuits, as well as many other uses (Ballance et al. 1978; Cunningham 1998). 

5.4 DISPOSAL 

The most significant amount of beryllium waste results from pollution control methods such as solid 

particulates scrubbers. Since beryllium is a valuable element, the most desirable method of handling 

beryllium wastes is to recycle them to the producers. Metal scrap, aqueous suspensions, and particulates 

are routinely recycled by Brush Wellman, Inc. at their production facility in Ohio (Brush Wellman 

2000a). 

The EPA has classified beryllium powder as a hazardous waste material (40 CFR Section 261.33). Under 

the Resource Conservation and Recovery Act (RCRA), compliance with labeling and disposal procedures 

as well as obtaining permits for discharges into air and water are required for beryllium powder. EPA 

standards require that atmospheric emissions from stationary sources be <10 g of beryllium over a 

24-hour period, and that the ambient concentration of beryllium near the stationary source be 

<0.01 μg/m3

. Beryllium solid waste should be placed into impermeable, sealed bags or containers (e.g., 

drums) that are labeled in accordance with the requirements of EPA regulations (Fishbein 1981). The 

EPA has also issued final regulations under the Clean Water Act for specific nonferrous metal 

manufacturing operations including beryllium processing facilities. These regulations limit the discharge 
BERYLLIUM 148 

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

of beryllium containing pollutants into navigable waters and into publically-owned treatment works 

(POTWs). Waste waters containing beryllium may therefore require treatment to reduce the 

concentration of beryllium. A typical treatment method for beryllium involves steps such as chemical 

precipitation, settling clarification, neutralization, filtration, and sludge dewatering (EPA 1982, 1988a). 

Waste waters that contain permissible levels of beryllium may be discharged into streams and POTW 

facilities (EPA 1982, 1988a). 

A significant amount of beryllium waste results from pollution control methods such as containment of 

solid particulates or aqueous suspensions resulting from air-scrubbing processes. According to the 

TRI99 (TRI99 2002), a total of 54,097 and 838,373 pounds of beryllium and beryllium compound wastes, 

respectively, were released to the environment by various industries in 1999 (see Chapter 6). Of the total 

release of beryllium, 98.5% was disposed on land (on-site), 1.4% was released to air, and 0.1% was 

released to surface water. Likewise, of the total release of beryllium compounds, 98.2% was disposed on 

land (on-site), 0.9% was released to air, 0.4% was released to surface water, and 0.5% was injected 

underground. An additional 20,081 and 72,118 pounds of beryllium and beryllium compound wastes, 

respectively, were transferred to off-site locations within the United States. Data regarding the trend in 

disposal practices for beryllium wastes in recent years were not located. 
BERYLLIUM 149 

6. POTENTIAL FOR HUMAN EXPOSURE 

6.1 OVERVIEW 

Beryllium has been identified in at least 535 of the 1,613 hazardous waste sites that have been proposed 

for inclusion on the EPA NPL (HazDat 2002). However, the number of sites evaluated for beryllium is 

not known. The frequency of these sites can be seen in Figure 6-1. Of these sites, 524 are located within 

the United States, 2 are located in the Territory of Guam, 2 are located in the U.S. Virgin Islands, and 

7 are located in the Commonwealth of Puerto Rico (not shown). 

Beryllium is naturally emitted to the atmosphere by windblown dusts and volcanic particles (EPA 1987). 

The major anthropogenic emission source to the environment is the combustion of coal and fuel oil, 

which releases particulates and fly ash that contain beryllium into the atmosphere (DOE 1996). Other 

anthropogenic processes, such as ore processing, metal fabrication, beryllium oxide production and use, 

and municipal waste combustion, release only a fraction of the amounts emitted from coal and oil 

combustion (Cleverly et al. 1989; EPA 1987; Fishbein 1981). Beryllium naturally enters waterways 

through the weathering of rocks and soils (EPA 1980). The sources of anthropogenic release of beryllium 

to surface waters include treated waste water effluents from beryllium or related industries and the runoff 

from beryllium-containing waste sites (EPA 1980, 1981). Deposition of atmospheric beryllium aerosols 

from both natural and anthropogenic sources is also a source of beryllium in surface waters. Some 

beryllium compounds are naturally present in soil, but the concentration of beryllium in localized soils 

can be increased because of the disposal of coal ash, municipal combustor ash, industrial wastes that 

contain beryllium, and deposition of atmospheric aerosols. 

Beryllium released to the atmosphere from combustion processes and ore processing will probably be 

present as beryllium oxide. Atmospheric beryllium particulates will eventually settle to the earth's surface 

by dry deposition or may be removed from the atmosphere by wet deposition (i.e., precipitation). Upon 

reaching water and soil, beryllium will probably be retained in an insoluble form in sediment and soil and 

will be generally immobile. Although chemical reactions may transform one beryllium compound into 

another, beryllium cannot be degraded by environmental reactions. However, the data regarding 

transformation reactions of beryllium in water and soil are limited. Bioconcentration of beryllium in 

plants and animals is low. In plants, uptake of beryllium appears to be restricted to the root 
Figure 6-1. Frequency of NPL Sites with Beryllium Contamination 

1-10 11-221-331-453 

Frequency of

NPL Sites 

Derived from HazDat 2002 
BERYLLIUM 151 

6. POTENTIAL FOR HUMAN EXPOSURE 

system; no significant translocation of beryllium to the above ground parts of the plant has been observed. 

Beryllium is not expected to bioconcentrate in aquatic animals (EPA 1980). 

The average concentration of beryllium in air in the United States is 0.03 ng/m3

, but the median 

concentration in cities is 0.2 ng/m3

 (Bowen 1979; EPA 1987). Dissolved beryllium was detected in 

groundwater at 352 of 504 sites in the United States (6.4% of sites) with an average concentration of 

13.6 μg/L. In surface water, dissolved beryllium was detected at 85 of 504 sites in the United States 

(16.1%) with an average concentration of 23.8 μg/L (EPA 2000a). The mean concentration of beryllium 

in U.S. soils is 0.6 mg/kg (Eckel and Langley 1988). The beryllium concentrations in both raw carrots 

and field corn grown in the United States were <25 μg/kg (fresh weight) (Wolnik et al. 1984). 

The general population is exposed to beryllium through inhalation of air and consumption of food and 

drinking water. The total beryllium intake by the general U.S. population cannot be estimated due to the 

lack of data regarding beryllium content in food. People who work in beryllium manufacturing, 

fabricating, and reclaiming industries are exposed to higher levels of beryllium than the general 

population. Smokers may also be exposed to higher levels of beryllium than nonsmokers because 

cigarette smoke contains beryllium (Reeves 1986). 

6.2 RELEASES TO THE ENVIRONMENT 

Releases of beryllium and beryllium compounds are required to be reported under Superfund 

Amendments and Reauthorization Act Section 313; consequently, data are available for this compound in 

the Toxics Release Inventory (TRI) (EPA 1995). According to the TRI, a total of 74,178 pounds 

(33,647 kg) of beryllium and 910,491 pounds (412,990 kg) beryllium compounds were released to the 

environment in 1999 (TRI99 2002). The TRI data should be used with caution because only certain types 

of facilities are required to report. This is not an exhaustive list. 

Beryllium has been identified in a variety of environmental media (air, surface water, leachate, 

groundwater, soil, and sediment) collected at 535 of 1,613 current or former NPL hazardous waste sites 

(HazDat 2002). 
BERYLLIUM 152 

6. POTENTIAL FOR HUMAN EXPOSURE 

6.2.1 Air 

Anthropogenic and natural emissions of beryllium to the atmosphere from various sources are reported in 

Table 6-1. In addition to ore processing, beryllium is also released into the atmosphere during the 

production and use of beryllium alloys and chemicals. Beryllium is released into the atmosphere from 

anthropogenic sources including the combustion of coal and fuel oil, the incineration of municipal solid 

waste (MSW), the production, use, and recycling of beryllium alloys and chemicals, and, to a minor 

extent, the burning of solid rocket fuel. According to the TRI data (TRI99 2002) shown in Tables 6-2 and 

6-3, 769 and 7,816 pounds of beryllium and beryllium compounds, respectively, were released in the 

atmosphere from alloys, chemicals, and user industries in 1999. 

Beryllium emissions from coal and fuel oil combustion account for a majority of the U.S. beryllium 

emissions from natural and anthropogenic sources (EPA 1987). The average beryllium concentration in 

coal is between 1.8 and 2.2 μg/g (EPA 1987). A study by the Department of Energy (DOE) and the 

University of North Dakota examined the emissions of toxic trace elements from coal-fired power plants 

(DOE 1996). The data in this study show that stack concentrations are 2–3 orders of magnitude greater 

than the range of ambient air concentrations for beryllium (DOE 1996). The median stack concentration 

for beryllium was 0.8 μg Be/m3

, and the average emission from the nine coal-fired power plants was 

22.6 pounds/year (range 0.49–55.8 pounds/year). The estimated total emissions of beryllium in 

1990 from the 3,266 fuel oil-fired power plants in the United States was 0.45 tons (0.41 metric tons) 

(DOE 1999a). TRI release data for electric utilities of 6,988 pounds of beryllium compounds were 

reported for 1999 (EPA 1987; TRI99 2002). The largest atmospheric releases of beryllium compounds 

were reported by Roxboro Steam Electric Plant in Person, North Carolina; Mt. Storm Power Station in 

Grant, West Virginia; and FirstEnergy Power Plant in Beaver, Pennsylvania with 487, 680, and 

1,250 pounds (0.22, 0.31, and 0.57 metric tons), respectively, for the year 1999. The TRI99 data should 

be used with caution since only certain types of facilities are required to report. This is not an exhaustive 

list (TRI99 2002). 

In 1986, there were 494 of 7,835 incinerated municipal waste streams containing beryllium in the United 

States (Behmanesh et al. 1992). There are 58 municipal Waste-to-Energy (WTE) facilities in the United 

States (DOE 1999a). At a municipal WTE facility in Commerce, California, stack emissions for 
BERYLLIUM 153 

6. POTENTIAL FOR HUMAN EXPOSURE 

Table 6-1. Anthropogenic and Natural Emissions of Beryllium and Beryllium
 

Compounds to the Atmospherea
 

Emission source Emission (tons/year)b 

Natural 

Windblown dust 5 

Volcanic particles 0.2 

Anthropogenicc,d 

Industry 0.6 

Metal Mining 0.2 

Electric utilities 3.5 

Waste and Solvent Recovery (RCRA) 0.007 

Total 9.507 

a

Adapted from Drury et al. 1978; EPA 1987; TRI99 2002 b

Units are metric tons.
 c

Data in TRI are maximum amounts released by each industry.

d

The sum of fugitive and stack releases are included in releases to air by a given industry.
 

RCRA = Resource Conservation and Recovery Act; TRI = Toxic Release Inventory 
Table 6-2. Releases to the Environment from Facilities that Produce, Process, or Use 

Reported amounts released in pounds per yeara 

Number 

Stateb 

of facilities Airc Water 

Underground injection Land 

Total on-site released 

Total off-sreleasee 

CA 3 0 No data No data No data 0 No da

IN 3 0 No data No data 2,650 2,650 2,4

LA 1 2 No data No data No data 2 No da

MO 1 0 No data No data 10 10 

NC 1 38 No data No data No data 38 No da

OH 6 721 27 No data 50,532 51,280 9,8OK 2 No data 23 No data 5 28 6,8

PA 1 1 7 No data No data 8 9

SC 1 7 No data No data 74 81 No daTN 1 No data No data No data No data No data No da

UT 1 0 No data No data 0 0 No da

WI 1 No data No data No data No data No data No da

Total 22 769 57 0 53,271 54,097 20,0

Source: TRI99 2002 aData in TRI are maximum amounts released by each facility.bPost office state abbreviations are used.cThe sum of fugitive and stack releases are included in releases to air by a given facility.dThe sum of all releases of the chemical to air, land, water, and underground injection wells.eTotal amount of chemical transferred off-site, including to publicly owned treatment works (POTW).
Table 6-3. Releases to the Environment from Facilities that Produce, Process, or Use Berylli

Reported amounts released in pounds per yeara 

Number 

Stateb 

of facilities Airc Water 

Underground injection Land 

Total on-site released 

Total off-sreleasee 

AL 6 419 250 No data 62,691 63,360 3AR 2 197 48 No data 9,130 9,375 

AZ 4 50 No data No data 16,421 16,471 1,6

FL 3 390 250 No data 5,745 6,385 

GA 5 764 0 No data 76,925 77,689 No da

IL 1 79 850 No data 8,500 9,429 No daIN 4 340 63 No data 40,019 40,422 3,8KY 5 351 1,221 No data 27,730 29,302 No da

MD 1 No data No data No data No data No data No da

MI 2 313 17 No data 15,000 15,330 2

MO 3 10 No data No data No data 10 5MS 1 2 20 4,100 19 4,141 

MT 1 250 No data No data 6,900 7,150 7

NC 4 817 403 No data 51,010 52,230 2

NM 4 112 77 No data 47,724 47,913 39,0

NY 1 20 0 No data 400 420 No da

OH 4 450 30 No data 25,846 26,326 11,4

PA 4 1,580 16 No data 8,700 10,296 6,4TN 2 256 250 No data 14,100 14,606 6

TX 1 19 0 No data 31,400 31,419 No da

UT 4 366 No data No data 299,952 300,318 

WI 1 10 5 No data No data 15 2
Table 6-3. Releases to the Environment from Facilities that Produce, Process, or Use Berylli

(continued) 

Reported amounts released in pounds per yeara 

Stateb 

Number of facilities Airc Water 

Underground injection Land 

Total on-site released 

Total off-sreleasee 

WV 9 861 10 No data 70,765 71,636 6,8

WY 1 160 No data No data 3,970 4,130 No daTotal 73 7,816 3,510 4,100 822,947 838,373 72,1

Source: TRI99 2002 aData in TRI are maximum amounts released by each facility.bPost office state abbreviations are used.cThe sum of fugitive and stack releases are included in releases to air by a given facility. dThe sum of all releases of the chemical to air, land, water, and underground injection wells. eTotal amount of chemical transferred off-site, including to publicly owned treatment works (POTW).
BERYLLIUM 157 

6. POTENTIAL FOR HUMAN EXPOSURE 

beryllium were measured at 0.2 μg/m3 (Hasselriis and Licata 1996). The stack emissions from individual 

municipal WTE facilities are about the same order of magnitude as stack emissions from individual coal 

fired power plants; however, the number of municipal WTE facilities in the United States is a factor of 

20 less than the number of coal fired power plants. 

Natural emission sources of beryllium include windblown dusts and volcanic particles. The beryllium 

amounts released to the atmosphere from these sources are comparable with anthropogenic sources (see 

Table 6-1). 

Beryllium has been identified in 9 air samples collected from 535 current or former NPL hazardous waste 

sites where it was detected in some environmental media (HazDat 2002). 

6.2.2 Water 

Anthropogenic sources of beryllium release to water include industrial waste water effluents. A
 

compilation of data for the beryllium levels in raw and treated waste water from various industrial sources
 

is available (EPA 1981). The concentrations of beryllium compounds are the highest in waste waters
 

from electric utility industries (TRI99 2002). The total reported amounts of beryllium and beryllium
 

compounds released to surface water for 1999 were 57 pounds (26 kg) and 3,510 pounds (1,592 kg),
 

respectively, as shown in Tables 6-2 and 6-3 (TRI99 2002).
 

Deposition of atmospheric beryllium is also a source in surface waters; however, the relative significance
 

of the contribution from this source, compared to industrial discharge to surface water, cannot be
 

assessed. Beryllium also enters the waterways from the weathering of rocks and soils (EPA 1980). Since
 

coal contains beryllium, it is also likely that beryllium will enter surface water via leaching of coal piles.
 

The industrial releases of beryllium and beryllium compounds into surface water are shown in
 

Tables 6-2 and 6-3, respectively. The largest releases to water were reported by electric utility facilities
 

such as St. Johns River Power Park (Duval, Florida), U.S. TVA Widows Creek Fossil Plant (Jackson,
 

Alabama), Baldwin Power Station (Randolph, Illinois), and U.S. TVA Cumberland Fossil Plant (Stewart,
 

Tennessee), which reported releases of 250, 250, 850, and 1,000 pounds (0.11, 0.11, 0.39, and 0.45 metric
 

tons), respectively (TRI99 2002). 
BERYLLIUM 158 

6. POTENTIAL FOR HUMAN EXPOSURE 

Beryllium has been identified in 92 surface water and 376 groundwater samples collected from 535 NPL 

hazardous waste sites, where it was detected in some environmental media (HazDat 2002). 

6.2.3 Soil 

Beryllium is naturally present in soils and sediments. Releases of beryllium and beryllium compounds to 

U.S. soils in 1999 as reported to the TRI are shown in Tables 6-2 and 6-3, respectively. According to the 

TRI, 53,271 pounds (52 metric tons) of beryllium and 822,947 pounds (179 metric tons) of beryllium 

compounds were released on-site to land by facilities that manufacture or process beryllium and beryllium 

compounds (TRI99 2002). An additional 20,081 pounds (9 metric tons) of beryllium and 72,118 pounds 

(33 metric tons) of beryllium compounds were released off-site to locations within the United States in 

1999 (TRI99 2002). 

Coal fly ash and municipal solid waste incinerator ash are disposed of in landfills and used in building 

materials (Kalyoncu 1998). Coal fly ash contains beryllium at levels of 46 mg beryllium/kg ash 

(Stadnichenko et al. 1961). About 100 million tons of coal fly ash containing various levels of beryllium 

are generated each year (Kalyoncu 1998). This translates to about 420 metric tons of beryllium disbursed 

as coal fly ash. 

Land application of sewage sludge containing higher than background concentrations of beryllium can be 

source of beryllium contamination of soil. Deposition of atmospheric aerosols on terrestrial surfaces is 

another source of beryllium in soil. Valberg et al. (1996) estimated the amount of time that it would take 

to double the ambient soil concentration of beryllium by dry deposition (at the point of maximum impact) 

near a MSW incinerator in Vermont. Their estimate was between 468 and 2,275 years, depending upon 

the ambient concentration of beryllium in the soil. Other quantitative data regarding the relative 

significance of these sources was not available. 

Beryllium has been identified in 353 soil and 193 sediment samples collected from 535 NPL hazardous 

waste sites, where it was detected in some environmental media (HazDat 2002). 
BERYLLIUM 159 

6. POTENTIAL FOR HUMAN EXPOSURE 

6.3 ENVIRONMENTAL FATE 

6.3.1 Transport and Partitioning 

Beryllium in air is attached to particulate matter whose residence time in air is dependant upon particle 

size. A study of stack emissions from coal combustion reported that most beryllium is found on particles 

with diameters of <2.5 μm (Gladney and Owens 1976). Particles of this size can remain airborne for 

approximately 10 days (Gladney and Owens 1976). The transport of beryllium from the atmosphere to 

terrestrial and aquatic surfaces occurs through wet and dry deposition (EPA 1987). By analogy to other 

elements, a typical dry deposition velocity may be estimated for beryllium particles over vegetative 

surfaces as 0.25 cm/second (EPA 1987). The dry deposition rate of aerosol particles is a function of 

particle size, wind speed, and surface roughness. The process of wet deposition of airborne beryllium 

consists of wash-out and rain-out; wash-out involves the scrubbing of particles from the air by rain and 

rain-out involves their attachment to aerosols in clouds. The portion of beryllium particles transported 

from the atmosphere by wet deposition has not been estimated. Beryllium was detected but not quantified 

in rainwater from Fresno, California, which suggests that transport of beryllium from the atmosphere to 

terrestrial and aquatic surfaces occurs by wet deposition (Salo et al. 1986). Beryllium containing soil can 

be resuspended in the atmosphere as a result of wind action. 

Beryllium is carried to rivers, lakes, and oceans by the process of land erosion. The amount of beryllium 

transported to surface waters from the land by wind-blown soil is estimated to be relatively small (Merrill 

et al. 1960). Acid deposition has been shown to accelerate chemical weathering of soil and bedrock into 

drainage outflow, increasing the mobility of beryllium (Jagoe et al. 1993). The estimated residence time 

of beryllium in ocean water, before it is removed from the aquatic phase by sedimentation or other 

removal processes, is between 150 and 570 years (Bowen 1979; Merrill et al. 1960). 

Beryllium binds strongly to soil fulvic acid; binding increases with increasing pH. Beryllium also forms 

complexes with marine fulvic acids at nearly neutral pH values (Esteves Da Silva et al. 1996a). However, 

beryllium has a much stronger affinity for clay minerals than for organic matter. Beryllium is usually 

associated in soil with aluminum sites on clay minerals rather than with iron oxides (Lum and Gammon 

1985). It tends to displace divalent cations with smaller charge-to-ionic radius ratios (Fishbein 1981). 

For pH values #6, the distribution of beryllium between solution and solids is related to sorption at 

surface sites. At pH values >6, the solute concentration of beryllium is strongly controlled by the 

solubility of Be(OH)2 (Aldahan et al. 1999). 
BERYLLIUM 160 

6. POTENTIAL FOR HUMAN EXPOSURE 

The sediment-water distribution coefficients (Kd) for beryllium are very high indicating a very low 

mobility in sediments. At pH values >6, Kd values are very high for most soils and sediments. For Lake 

Michigan sediments, Kd ranged between 105 and 106 (Hawley et al. 1986). Beryllium may accumulate in 

the surface organic layer of the sediment profile; however, there is no indication as to whether the organic 

matter content of sediment affects Kd (Lum and Gammon 1985). The presence of organic matter did not 

significantly affect the Kd for saline systems (You et al. 1989); in seawater, Kd is, on average, between 

316,000 and 794,000 (Hawley et al. 1986). 

In highly alkaline soils, the mobility of beryllium may increase as a result of the formation of soluble 

hydroxide complexes, such as [Be(OH)4 ]

2- (Callahan et al. 1979; Cotton and Wilkinson 1980). In acidic 

soils (e.g., forest ecosystems), dissolved Be2+ has been found to be the prevailing beryllium species in the 

soil solution, and it should be relatively mobile in these environments (Krám et al. 1998). However, 

leaching would not be expected to occur in less acidic soils (Hayes and Traina 1998). 

The concentration of beryllium in plants is very low (see Section 6.4.4). Soluble forms of beryllium must 

be present for uptake to occur in plants. For collard seedlings, beryllium remains in the roots, and only 

small portions were translocated to above ground portions (Kaplan et al. 1990). Romney and Childress 

(1965) examined uptake of 7

Be in beans, barley, sunflowers, and tomato plants. Over 95% of 7Be was 

found in the roots; very little was translocated to the foliage and fruits (Romney and Childress 1965). 

The Enrichment Ratio (ER) of beryllium in oat grain and in alfalfa grown in both microcosms and field 

plots amended with beryllium containing fly ash was 1 (Tolle et al. 1983). 

Beryllium does not bioconcentrate in aquatic organisms. A measured bioconcentration factor (BCF) of 

19 was reported for beryllium in bluegill fish (EPA 1980). Other investigators have reported a BCF of 

100 for freshwater and marine plants, vertebrates, and fish (Callahan et al. 1979). Comparisons of the 

beryllium levels in bottom-feeding biota and surfaces sediments from Lake Pontchartrain, Louisiana, 

indicate similar, but somewhat lower, beryllium concentrations in biota (Byrne and DeLeon 1986). Very 

low bioaccumulation for beryllium was observed in southern toads (Bufo terrestris) exposed directly to 

elevated levels of beryllium and other trace metals from a coal fly ash basin (Hopkins et al. 1998). No 

evidence of the bioaccumulation of beryllium in the food chain of humans was located in the literature 

(Fishbein 1981). 
BERYLLIUM 161 

6. POTENTIAL FOR HUMAN EXPOSURE 

6.3.2 Transformation and Degradation 

As an element, beryllium does not degrade in the environment; it can only change its form. 

6.3.2.1 Air 

The atmospheric emission of beryllium during ore processing is likely to occur as: beryllium, beryllium 

ore dust, beryllium hydroxide, Be(OH)2; beryllium oxide, BeO; sodium fluoroberyllate, (NH4)2BeF4; and 

beryllium fluoride, BeF2 (Fishbein 1981); from ceramic plants, atmospheric emissions are typically 

beryllium or beryllium oxide (Fishbein 1981). The form of beryllium emitted into the atmosphere from 

thermal processes is typically beryllium oxide (EPA 1998). It is unlikely that beryllium oxide in air will 

react with sulfur or nitrogen oxides to produce beryllium sulfates or nitrates. 

6.3.2.2 Water 

Beryllium exhibits only the +2 oxidation state in water. The reaction of beryllium in water is controlled 

by chemical speciation by which one species is converted to another. Beryllium is highly hydrated in 

acid solutions, which is a consequence of its high charge to size ratio. The speciation of beryllium in 

solution is: [Be(H2O)4 ]2+, Be2(OH)3+, Be3(OH)3

3+, and possibly Be5(OH)73+ in acid solution (i.e., pH#6); 

and [Be(OH)4]

2- in basic solution (i.e., pH>8) (Cotton and Wilkinson 1980). In the pH range of 6–8, 

typical of most waters, the speciation of beryllium is controlled by the formation solid beryllium 

hydroxide, Be(OH)2, which has a very low solubility (solubility product, Ksp=10-21). Table 6-4 illustrates 

several precipitation reactions for beryllium under a neutral environment. 

Other transformations of environmental importance are the formation of insoluble basic carbonates, such 

as (BeCO3)2Be(OH)2, formed by reaction of dissolved carbonate with beryllium solutions and the 

formation of beryllium sulfate (i.e., BeSO4) formed by reaction of soluble sulfates with beryllium 

solutions. 
BERYLLIUM 162 

6. POTENTIAL FOR HUMAN EXPOSURE 

Table 6-4. Precipitation of Beryllium Compounds in a Neutral (pH 6.5–9.5)
 

Environment
 

Ammonium tetrafluoroberyllate Remains soluble in a neutral 

(Ammonium beryllium fluoride) environment 

(NH4)2BeF4 —> 2[NH4]+

aq + [BeF4]

2-

aq 

Excess H2O
 

pH 7
 

Beryllium oxide Forms insoluble beryllium 

hydroxide in a neutral 

BeO + H2O —> Be(OH)2 environment 

Excess H2O
 

pH 7
 

Beryllium hydroxide Beryllium hydroxide is 

insoluble in a neutral 

Be(OH)2 —> no reaction environment 

Excess H2O
 

pH 7
 

Beryllium fluoride Remains soluble in a neutral 

environment 

BeF2 + 2 H2O —> [BeF2(H2O)2]aq and other complexes 

Excess H2O
 

pH 7
 

Beryllium nitrate trihydrate Forms insoluble beryllium 

hydroxide in a neutral 

Be(NO3)2#3H2O + 2MOHa

 —> Be(OH)2 + 2[M]+

aq + 2[NO3]

-

aq + 3H2O environment 

Excess H2O
 

pH 7
 

Beryllium sulfate tetrahydrate Forms insoluble beryllium 

hydroxide in a neutral 

BeSO4#4H2O + 2MOHa

 —> Be(OH)2 + 2[M]+

aq + [SO4]

2-

aq + 4H2O environment 

Excess H2O
 

pH 7
 
BERYLLIUM 163 

6. POTENTIAL FOR HUMAN EXPOSURE 

Table 6-4. Precipitation of Beryllium Compounds in a Neutral (pH 6.5–9.5)
 

Environment (continued)
 

Beryllium oxalate trihydrate Forms insoluble beryllium 

hydroxide in a neutral 

BeC2O4#3H2O + 2MOHa

 —> Be(OH)2 + 2[M]+

aq + [C2O4]

2-

aq + 3H2O environment 

Excess H2O
 

pH 7
 

Beryllium Basic Acetateb Forms insoluble beryllium 

hydroxide in a neutral 

Be4O(C2H3O2)6 + 6MOHa

 + H2O —> 4Be(OH)2 + 6[M]+

aq + 6[C2H3O2]

- environment 

aq 

Excess H2O
 

pH 7
 

Source: EPA 1998 

a

MOH is a base; M in MOH signifies a cation such as sodium (Na) or potassium (K). b

Beryllium basic acetate is not a true basic salt; it is a covalent compound. 
BERYLLIUM 164 

6. POTENTIAL FOR HUMAN EXPOSURE 

6.3.2.3 Sediment and Soil 

Typical transformation processes for beryllium in soil include precipitation, complexation, and anion 

exchange. Important factors affecting the transformation of beryllium in soils and sediments include: 

pH, ionic strength (i.e., salinity), concentration and distribution of species, composition of the mineral 

matrix, organic matter, biological organisms, and temperature (see Section 6.3.1). Data suggesting the 

biotransformation of beryllium or its compounds in soil were not located. 

6.3.2.4 Other Media 

No data were located on the transformation of beryllium in media other than air, water, sediment, and soil 

in the literature. 

6.4 LEVELS MONITORED OR ESTIMATED IN THE ENVIRONMENT 

6.4.1 Air 

Beryllium in the ambient air is measured at many local, state, and national air monitoring stations across 

the United States. The data are available from the Storage and Retrieval of Aerometric Data database 

(EPA 1987). The detection limit for aerometric determination of beryllium is 0.03 ng/m3

, and annual 

averages at most of these monitoring stations are listed below this concentration. Measurements at 

100 U.S. locations indicated an average daily beryllium concentration of <0.5 ng/m3

 (Drury et al. 1978; 

Fishbein 1981). Between 1982 and 1992, annual averages of beryllium in air ranged from 0.02 to 2 ng/m3 

in the urban Detroit, Michigan area. The ambient concentrations of beryllium were quite similar for all 

land use categories (e.g., residential, commercial, and industrial). In 1985, in Jacksonville, Florida, 

beryllium was below the limit of detection in air (Del Delumyea et al. 1997). 

The ambient concentration of beryllium found in air near power stations in Castellon, Spain ranged from 

not detected to 1.61 ng/m3

 (Boix et al. 2001). Beryllium concentrations in atmospheric particulate 

samples in and around a beryllium processing facility near Navi Mumbai, India were 0.48±0.42 ng/m3 

(N#397). The levels of beryllium during the monsoon season were comparatively lower and often were 

below the detection limit (Thorat et al. 2000). 
BERYLLIUM 165 

6. POTENTIAL FOR HUMAN EXPOSURE 

6.4.2 Water 

Beryllium was detected in 2,760 out of 50,000 U.S. Geological Survey ambient surface water monitoring 

stations through the year 1988 with a mean concentration of 1.9 μg/L (Eckel and Jacob 1988). The 

National Drinking Water Contaminant Occurrence Database (NDOD), which contains data from ambient 

water supplies, lists the number of detections of beryllium in surface water at several locations around the 

United States. In lakes/reservoirs, dissolved beryllium was detected at 13 of 137 sites (9.5% of sites) with 

an average concentration of 1.1±0.4 μg/L (EPA 2001). In spring waters, dissolved beryllium was 

detected at 4 of 66 sites (6.1% of sites) with an average concentration of 99.3±42.1 μg/L (EPA 2000a). In 

other surface waters, dissolve beryllium was detected at 227 of 1,539 sites (14.7% of sites) with an 

average concentration of 20.8±36.1 μg/L; total beryllium was detected at 182 of 943 sites (19.3% of sites) 

with an average concentration of 4.4±35.1 μg/L (EPA 2001). The median total beryllium concentration 

of Great Lakes water samples ranged from <4 to 120 ng/L. The percentage of beryllium in suspended 

particulates of Great Lakes water samples ranged from 2 to 88% and averaged about 50% (Rossmann and 

Barres 1988). Beryllium concentrations measured in the Houston Ship Channel ranged from 8 to 24 ng/L 

(Saleh and Wilson 1999). The concentration of total beryllium in seawater ranges from 0.02 to 0.9 ng/L, 

with an average of <0.5 ng/L (Measures and Edmond 1986; Merrill et al. 1960). 

The NDOD lists the number of detections of beryllium in groundwater water at several locations around 

the United States. In groundwater, dissolved beryllium was detected at 262 of 4,177 sites (6.6% of sites) 

with an average concentration of 13.0±50.3 μg/L; total beryllium was detected at 30 of 334 sites (9.0% of 

sites) with an average concentration of 1.7±1.8 μg/L (EPA 2000a). The median concentration of 

beryllium in groundwater samples taken around the Denver, Colorado metropolitan area in 1993 was 

measured at <1 μg/L (Bruce & McMahon 1996). Beryllium has been identified in 376 groundwater 

samples collected from 535 NPL hazard waste sites, where it was detected in some environmental media 

(HazDat 2002). 

Rainwater in Australia had an average beryllium concentration of 0.05–0.08 μg/L (Meehan and Smythe 

1967) and an upland environment in Great Britain had an average concentration of <0.06 μg beryllium/L 

(Neal et al. 1992). 

The average concentrations of beryllium in bottled and tap water in the United States were <0.1 and 

0.013 μg/L, respectively. Table 6-5 summarizes some selected data on the beryllium content of drinking 

water (Vaessen and Szteke 2000). 
BERYLLIUM 166 

6. POTENTIAL FOR HUMAN EXPOSURE 

6.4.3 Sediment and Soil 

Beryllium is the 44th most abundant element in the Earth’s crust. The average beryllium concentration in 

the Earth’s crust is approximately 2–5.0 mg/kg (Drury et al. 1978; Griffitts and Skilleter 1990; Krám et 

al. 1998; Mason and Moore 1982; Reeves 1986). Beryllium occurs in silicate minerals and feldspar 

minerals. The greatest known concentrations of beryllium are found in certain pegmatite bodies. 

Beryllium ores can contain several thousand mg beryllium per kg solid (Fishbein 1981). Shacklette and 

Boerngen (1984) reported the average and range of beryllium concentrations in soils and other surficial 

materials in the conterminous United States as 0.63 and <1–15 mg/kg, respectively. Frink (1996) 

summarized several different studies and reported that the most likely concentration of beryllium in 

uncontaminated soils (in the Northeast United States) ranges from <1 to 7 mg/kg. The average 

concentrations of beryllium in the O or A horizons (sandy loam) and the B horizon (clay) in Maryland 

were 0.71 and 0.46 mg/kg respectively (Sparling and Lowe 1996). The average and range of beryllium 

concentrations in Florida soils were 0.46 mg/kg and 0.01–5.92, respectively (Chen et al. 1999). The 

average beryllium concentration in California soils was measured as 1.14 mg/kg (Chen et al. 1999). 

There are few beryllium rich soils in the United States, and these areas are in sparsely settled areas that 

are not important for food production (Griffitts and Skilleter 1990). The concentration of beryllium in 

soil around beryllium processing facilities in Navi Mumbai, India ranged from 1.42 to 2.75 μg/g (Thorat 

et al. 2000). These levels were comparable to background levels reported in the literature. 

In bottom sediments of the Detroit River and western Lake Erie, concentrations of beryllium ranged from 

0.1 to 3.8 μg/g beryllium (Lum and Gammon 1985). The beryllium levels in the sediments of Lake 

Pontchartrain, Louisiana were 0.05–0.5 μg/kg (dry weight) (Byrne and DeLeon 1986). The concentration 

of beryllium in sediments from the Neosho River in southeastern Kansas ranged from 0.52 to 1.1 μg/g dry 

weight in 1992 (Allen et al. 2001). Beryllium has been identified in 353 soil and 193 sediment samples 

collected from 535 NPL hazardous waste sites, where it was detected in some environmental media 

(HazDat 2002). 
Table 6-5. Beryllium Content of Drinking Water 

Content (μg/kg) 

Number of 

Product samples Mean Range Technique R

Mineral water (bottled) 

Spain: 

Lanjaron 3 — 0.12±0.01 IEF Capitan et al. 

Ortigosa del Monte 3 <0.6 <0.06 IEF Capitan et al. 

United States: 

All samples 72 <0.1 <0.1–5.2 ICP Allen et al. 198

Domestic samplesa 18 <0.1 <0.1–0.2 ICP Allen et al. 198

European samplesb 54 <0.1 <0.1–5.2 ICP Allen et al. 198

Poland: 

Nieszawa 3 0.17 — ET-AAS Szczepaniak a

Zywiec Zdrój 3 0.15 — ET-AAS Szczepaniak a

Tap Water 

Spain-Granada 3 — 0.09±0.01 IEF Capitan et al. 

Germany-Mainz — 0.008c <0.005±0.009 ET-AAS Reichert 1973 

Germany-Weisbeden — — 0.034±0.002 ET-AAS Sauer and Lie
Table 6-5. Beryllium Content of Drinking Water (continued) 

Content (μg/kg) 

Product 

Number of samples Mean Range Technique R

Saudi Arabia-Riyadh (schools) 

59 1.24c 0.4–2.17 ICP-MS Al-Saleh 1996 

The Netherlands 266 

91 

<0.1 <0.05 

<0.1–0.2 

<0.05–0.21 

— ICP-MS 

Fonds et al. 19Van de Veld-K

United States — 0.013c 0.01–0.7 — APHA 1992 

Source: Vaessen and Szteke 2000 anine brands b28 brands carithmetic mean — = Not specified; ET-AAS = electrothermal atomic absorption spectrometry; ICP = inductively coupled plasma spectroscopy; ICP-MS = 

plasma mass spectrometry; IEF = ion exchange fluorimetry 
BERYLLIUM 169 

6. POTENTIAL FOR HUMAN EXPOSURE 

6.4.4 Other Environmental Media 

The beryllium concentration in several foods, fruits, and fruit juices from around the world are shown in 

Tables 6-6 and 6-7. The median concentration of beryllium in the 38 foods listed in Table 6-6 is 

22.5 μg/kg fresh weight (excluding kidney beans) and the range of concentrations is <0.1–2,200 μg/kg 

fresh weight. The highest concentrations (in μg/kg fresh weight) were reported for kidney beans (2,200), 

crisp bread (112), garden peas (109), parsley (77), and pears (65). The average concentration of 

beryllium in fruit and fruit juices listed in Table 6-7 is 13.0 μg/L, and the concentrations ranged from not 

detected to 74.9 μg/L. 

The beryllium concentration in the tissue of bottom fish (e.g., English sole or Parophrys vetulus) from 

Commencement Bay, Tacoma, Washington was 6 μg/kg (Nicola et al. 1987). Beryllium levels in oysters 

and clams in Lake Pontchartrain, Louisiana were 0.051 and 0.083–0.38 μg/g dry weight, respectively 

(Byrne and DeLeon 1986). A U.S. FDA survey of concentrations of beryllium and other elements in 

oysters and clams collected from U.S. coastal areas in use for shellfish production ranged from not 

detected to 0.002 mg/kg wet weight (Capar and Yess 1996). In 1991, the concentration of beryllium in 

mussels species from the Neosho River, Kansas were 0.02–0.04, not detected–0.02, 0.03, and 

0.02–0.04 μg/g dry weight for pimpleback (n=3) sampled at Cottonwood River; Kansas, monkeyface 

(n=2) sampled at Humboldt, Kansas; monkeyface (n=1) sampled at Leroy, Kansas; and monkeyface (n=4) 

sampled at Oswego, Kansas, respectively (Allen et al. 2001). 

The concentration of beryllium in pipping black-crowned night herons from Pea Patch Island in Delaware 

Bay, a major shipping area that receives anthropogenic releases of toxic substances, ranged from not 

detected to 0.028 μg/g dry weight. At Middle Island (a coastal reference site without contamination 

located in Rehoboth Bay, Delaware), the concentration of beryllium in pipping black-crowned night 

herons ranged from not detected to 0.021 μg/g dry weight (Ratter et al. 2000). 

Beryllium has been detected in orchard leaves and in various trees and shrubs in the United States at 

concentrations of 26 and <1 μg/kg, respectively (IARC 1980). The beryllium content of 

macrohydrophytes derived from various habitats in Poland ranged from 0.7 to 136.6 μg/g. The beryllium 

concentrations varied with the plant species and the particular degree of water contamination in their 

respective environments (Sarosiek and Kosiba 1993). Beryllium levels were below detection limits (not 
BERYLLIUM 170 

6. POTENTIAL FOR HUMAN EXPOSURE 

Table 6-6. Beryllium Content of Various Fresh Foods 

Concentration (μg 

Be/kg fresh weight) 

Number of 

Product samples Mean Range Technique Reference 

Bananas, pulp 400 4.2 ND–18 — Cowgill 1981 

Beans 3 0.07 ND–0.07 F Meehan and Smythe 1967 

Beans, kidney — 2,200a — ICP-AES Awadallah et al. 1986 

Cabbage 1 0.2 — F Meehan and Smythe 1967 

Cabbage 95 0.091 ND–0.50 ICP-MS Bibak et al. 1999 

Cane sugar: 

brown — 30 — — Hamilton and Minski 1973 

demerara — 6 — — Hamilton and Minski 1973 

refined — 2 — — Hamilton and Minski 1973 

granulated — 0.2 — — Hamilton and Minski 1973 

Carrots, raw — <25 — — Wolnik et al. 1984 

Clams, hardshell 31 2±3 — ICP-AES Caper and Yess 1996 

Clams, softshell 10 <2 — ICP-AES Caper and Yess 1996 

Crabs 6 15 10–20 F Meehan and Smythe 1967 

Crisp bread — 112a — Flame AAS Zorn and Diem 1974b 

Coriander — 34a — ICP-AES Awadallah et al. 1986 

Corn, field — <25 — — Wolnik et al. 1984 

Dill — 59a — ICP-AES Awadallah et al. 1986 

Egg plant — 26a — ICP-AES Awadallah et al. 1986 

(aubergine) 

Fish, whole: 

Mullet 8 11 1.6–19 F Meehan and Smythe 1967 

Blackfish 4 11 3.7–18 F Meehan and Smythe 1967 

Fish, whole: 

Mullet 2 1.5 ND–2.6 F Meehan and Smythe 1967 

Blackfish 1 0.4 — F Meehan and Smythe 1967 

Garden pea — 109a — ICP-AES Awadallah et al. 1986 

Green pepper — 42a — ICP-AES Awadallah et al. 1986 

Hen eggs, yolk 1 0.2 — F Meehan and Smythe 1967 

Hen eggs, yolk, and 1 0.06 — F Meehan and Smythe 1967 

white 

Honey 

Eucaliptus — 0.18±0.09 — ICP-MS Bettinelli et al. 2000 

Robinia — 0.38±0.02 — ICP-MS Bettinelli et al. 2000 
BERYLLIUM 171 

6. POTENTIAL FOR HUMAN EXPOSURE 

Table 6-6. Beryllium Content of Various Fresh Foods (continued) 

Concentration (μg 

Be/kg fresh weight) 

Number of 

Product samples Mean Range Technique Reference 

Lettuce — 16a — Flame AAS Zorn and Diem 1974 

Meat 3 4 4–5 GC-ECD Kaiser et al. 1972 

Milk 100 0.2 ND–0.7 F Meehan and Smythe 1967 

Mushrooms 1 1.6 — F Meehan and Smythe 1967 

Mushrooms, 1,303 9 <5–36 ET-AAS Seeger et al. 1984 

European wild 

Orange juices — <1 — — McHard et al. 1980 

Oysters 59 0.6 0.2–5.4 F Meehan and Smythe 1967 

Oysters, east coast 93 <2 — ICP-AES Capar and Yess 1996 

United States 

Oysters, west coast 40 <2 — ICP-AES Capar and Yess 1996 

United States 

Parsley — 77a — ICP-AES Awadallah et al. 1986 

Peanuts, kernels 2 0.5 0.3–0.8 F Meehan and Smythe 1967 

Pears — 65a — ICP-AES Awadallah et al. 1986 

Potatoes — 59a — ICP-AES Awadallah et al. 1986 

Potatoes — 33a — Flame AAS Zorn and Diem 1974 

Potatoes 41 0.4–0.6 0.2–1.4 ET-AAS Hofele et al. 1994 

Rice 3 4 3–5 GC-ECD Kaiser et al. 1972 

Rice, peeled — 72a — Flame AAS Zorn and Diem 1974 

Tomatoes 1 0.2 — F Meehan and Smythe 1967 

Tomatoes 17a — Flame AAS Zorn and Diem 1974 

Vegetable marrow — 20a — ICP-AES Awadallah et al. 1986 

(pumpkin) 

a

Original data based on dry weight; concentrations are recalculated to fresh weight. 

— = not specified; AAS = atomic absorption spectroscopy; AES = atomic emission spectroscopy; 

ET-AAS = electrothermal atomic absorption spectrometry; F = fluorimetry; GC-ECD = gas chromatography electron 

capture detection; ICP-AES = inductively coupled plasma-atomic emission spectroscopy; ICP-MS = inductively 

coupled plasma-mass spectrometry; ND = not detected 
BERYLLIUM 

6. POTENTIAL FOR HUMAN EXPOSURE 

172 

Table 6-7. Beryllium Content of Various Fruits and Fruit Juices 

Product Number of samples Mean (μg/L) Range 

Apple juice 4 22.5 ND–43.6 

Citrus fruit 

Ruby red grapefruit 1 1.3 — 

Lime 1 ND — 

Tangerine 1 0.8 — 

Grape cultivars 3 4.4 <0.1–7 

Lemon products 

CA lemon 1 17.4 —
 

Bottled lemon 1 17.0 —
 

Lemonade 1 55.3 —
 

Orange juice 5 2.8 ND–2.8
 

Papaya (pulp) 3 74.9 64.5–84.1
 

Pear (pulp) 1 37.3 —
 

Red currant 1 1.1 —
 

Stone fruit (pulp)
 

Apricot 1 <0.1 —
 

Peach 1 ND —
 

Plum 1 1.6 —
 

Prune 1 3.6 —
 

Sour cherry 1 1.5 —
 

Tomato sauce 2 42.4 39.8–45.0 

Tropical fruit 

Banana 1 1.5 — 

Kiwi 1 3 — 

Mango 1 4.5 — 

Pineapple 1 <0.1 — 

Source: Barnes 1997 

— = not specified; ND = not detected 
BERYLLIUM 173 

6. POTENTIAL FOR HUMAN EXPOSURE 

specified) in vegetation in the immediate vicinity of a municipal solid waste (MSW) incinerator near 

Catalonia, Spain (Meneses et al. 1999). 

Beryllium levels of 0.47–0.74 μg per cigarette have been detected in three brands of German cigarettes; 

2–10% of the beryllium was found in the cigarette smoke (Reeves 1986). In a literature review 

undertaken by Smith et al. 1997, yields of 0–0.0005 μg beryllium per cigarette have been reported for 

domestic cigarette brands. Beryllium was detected in only 4 of 12 studies in which it was a target element 

(Smith et al. 1997). 

The beryllium concentration in coal ash is on average 46 mg/kg in the United States (Stadnichenko et al. 

1961). Beryllium concentrations in ammonia, nitrate, and phosphorus fertilizers used in agriculture 

ranged from <0.2 to 13.5 μg/g (Raven and Loeppert 1997). 

6.5 GENERAL POPULATION AND OCCUPATIONAL EXPOSURE 

The general population is exposed to trace amounts of beryllium by inhalation of air and ingestion of 

drinking water and food. If the average concentration of beryllium in air is assumed to be <0.03 ng Be/m3 

(see Section 6.4.1), and it is further assumed that a normal U.S. adult inhales approximately 20 m3 of air 

per day, then the inhalation exposure for a U.S. adult would be approximately <0.6 ng Be/day. This value 

may be somewhat higher for persons living near sources of beryllium emission. Similarly, if the 

concentration of beryllium in average U.S. drinking water is 0.5 μg/L (see Section 6.4.2), and the 

consumption rate of drinking water by a normal adult is assumed to be 2 L/day, the exposure from 

drinking water would be 1 μg per day. Reliable data regarding the daily exposure rate to beryllium from 

food consumption are lacking. It has been estimated that the daily intake of beryllium from U.S. food is 

0.12 μg (EPA 1987). This estimate is based on an arbitrary value for beryllium content of a total diet 

sample of 0.1 ng per g food and a daily consumption of 1,200 g of food (EPA 1987). In a study 

examining the trace element concentrations of foodstuffs in Tarragona, Spain, beryllium was below the 

detection limit (0.02 μg/g) in the following food groups: meat, seafood, cereals, seeds, vegetables, roots/ 

tubers, fruits, milk, dairy products, eggs, and sugar (Llobet et al. 1998). In another study examining, the 

trace element concentrations of food samples via hospital diets in Japan, the average daily intake of 

beryllium was determined to be 84.4 μg/day (Muto et al. 1994). Other investigators have reported the 

total daily intake of beryllium in the range of 5–100 μg/day (Emsley 1998; Tsalev and Zaprianov 1984; 

Vaessen and Szteke 2000). 
BERYLLIUM 174 

6. POTENTIAL FOR HUMAN EXPOSURE 

The mean concentration of beryllium in urine of about 500 nonoccupationally exposed individuals in the 

United States according to the 3rd National Health and Nutrition Examination Survey was 0.22 μg/g of 

creatinine (Paschal et al. 1998). Other studies reported mean urinary beryllium concentrations ranging 

from <0.03 to 0.4 μg/L for persons not occupationally exposed (Apostoli and Schaller 2001). Tsalev and 

Zaprianov (1984) reported that approximately 10 μg Be/day is excreted (on average) in human feces. 

Using the estimated daily fecal concentration, the exposure to beryllium by this method is within the 

range of estimates determined from total diet studies as discussed previously. Beryllium concentrations 

in other human tissues and fluids are: blood 0.01–3.6 μg/L, bone 3 μg/kg, hair 5–8 μg/kg, liver 2 μg/kg, 

muscle 0.8 μg/kg, nails <10 μg/kg, plasma or serum <4 μg/L, and tooth <0.01 μg/kg (Emsley 1998; 

Tsalev and Zaprianov 1984). 

In a study of German cigarettes, tobacco was found to contain 0.47–0.74 μg beryllium per cigarette and 

2–10% passes into the smoke during smoking (Reeves 1986). Some cigarettes contain small amounts of 

beryllium, and increases of blood and urine beryllium have been associated with smoking (Tsalev and 

Zaprianov 1984). In another review focusing on cigarettes from the United States, yields of 0–0.0005 μg 

Be per cigarette have been reported in 4 of 12 studies of smoke measurements; however, 8 of 12 studies 

failed to detect beryllium at any concentration (Smith et al. 1997). Nevertheless, smokers may have a 

higher probability of exposure to beryllium than the nonsmoking population. 

People who work in industries where beryllium is present have a greater probability of inhalation 

exposure than nonoccupational groups. The estimated daily-weighted average beryllium exposure levels 

for some workers in a plant that extracted and produced beryllium metal were >50 μg/m3

 during the 

mid-1960s. Beryllium exposure levels were >30 μg/m3

 during the mid-1970s. After 1977, this plant 

complied with the OSHA maximum TWA concentration of 2 μg/m3

 (Kriebel et al. 1988a). The TWA 

personal air concentration for beryllium in a precious metal refinery in 1983 ranged from 0.22 to 

42.3 μg/m3

 (Cullen et al. 1987). Recent occupational exposure measurements of beryllium at the Rocky 

Flats Environmental Technology Site in Colorado were conducted in the main beryllium production 

building. Mean concentrations of beryllium were measured for area and breathing zone monitors as 

0.16 and 1.04 μg/m3

, respectively (Stange et al. 1996a). At the Cardiff Atomic Weapons Establishment in 

the United Kingdom, annual mean area and personal sampling concentration ranges of beryllium were 

from 0.02–0.32 and 0.09–0.72 μg/m3

, respectively, over the period from 1961 to 1997 (Johnson et al. 

1999). 
BERYLLIUM 175 

6. POTENTIAL FOR HUMAN EXPOSURE 

Workers who do not change their work clothes at the end of the work day can increase the probability of 

home contamination with beryllium. Fabrics experimentally exposed at a beryllium production worksite 

contained up to 2.8 mg Be/m2

 (NIOSH 1995). Workers’ family members may be exposed when workers 

come home wearing beryllium-contaminated clothing. Resuspended beryllium dust concentrations in air 

from unwashed clothing can reach levels of 0.64 μg/m3

. The shaking of contaminated clothes can 

administer an inhalation dose of approximately 17 μg beryllium (NIOSH 1995). In another study, 

beryllium concentrations in machine shop workers’ personal vehicles were measured. The highest 

concentrations of beryllium were measured on the driver’s floor of the workers’ vehicles at 

19 μg/Be/foot2

 (Sanderson et al. 1999). 

It is likely that dental technicians who work with beryllium-containing dental alloys without using 

appropriate handling safeguards may be exposed to higher levels of beryllium than the normal population 

(Bauer et al. 1988). 

A National Occupational Exposure Survey conducted by NIOSH during 1981–1983 estimated that 

13,869 workers were potentially exposed to beryllium and 7,045 workers to beryllium compounds in the 

workplace (NIOSH 1989a). 

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 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). 

Specific information on the exposure of children to beryllium is limited. An x-ray health survey was 

conducted in 1948 in the neighborhood surrounding a beryllium manufacturing facility in Lorain, Ohio. 
BERYLLIUM 176 

6. POTENTIAL FOR HUMAN EXPOSURE 

In this survey, 2,000 children were examined, and none of the children exhibited signs of chronic 

berylliosis disease (AEC 1948). As with adults in the general population, small exposures in children 

occur from normal ingestion of food and drinking water and inhaling air. These exposures may be higher 

in areas with naturally high beryllium soil levels, and near beryllium processing sites, electric power 

plants, and waste sites containing beryllium. A study by Krachler et al. (1999a) provides suggestive 

evidence that beryllium is transferred across the placenta and excreted via breast milk. The levels of 

beryllium in umblical cord serum and in colostrum were higher than in maternal serum. The average 

concentrations of beryllium in the umbilical cords of healthy newborn children were measured for arterial 

(1.3 μg/L), venous (0.8 μg/L), and mixed (0.6 μg/L) sera (Krachler et al. 1999b). No information on 

beryllium levels in amniotic fluid, meconium, or neonatal blood was located. 

At waste sites, beryllium that is found in excess of natural background levels is most likely to be in soil, 

and presents a special hazard for young children. Hand-to-mouth activity and eating contaminated dirt 

will result in oral exposure to beryllium. The hazard in this case depends on the form of beryllium 

present at the waste site. Beryllium in soil at waste sites is almost entirely in the form of insoluble oxides 

and hydroxides of beryllium which would be expected to be less available than more soluble forms (see 

Section 6.3.1). 

Other home exposures are unlikely since no household products or products used in crafts, hobbies, or 

cottage industries contain significant amounts of beryllium except in copper-beryllium wire, which is 

used in and around the home in electronics or other electrical devices. 

Beryllium exposure to children from parents’ work clothes, skin, hair, tools, or other objects from the 

workplace is possible if the parent uses beryllium at work. In a report to Congress by NIOSH, several 

historical cases of home contamination by beryllium were reported (NIOSH 1995). The most recent case 

was in 1992, suggesting that cases of beryllium home contamination may still be occurring. The majority 

of these cases were from the contamination of machinist workers’ clothing with beryllium dust (NIOSH 

1995). 
BERYLLIUM 177 

6. POTENTIAL FOR HUMAN EXPOSURE 

6.7 POPULATIONS WITH POTENTIALLY HIGH EXPOSURES 

Several populations are at high risk for beryllium exposure. Individuals with the highest risk include 

people who are occupationally exposed to beryllium from manufacturing, fabricating, or reclaiming 

industries. There have been no reports of diseases attributable to beryllium exposure as a result of 

beryllium ore mining operations (Eisenbud and Lisson 1983; EPA 1987; Hamilton and Hardy 1974). 

People living near beryllium-emitting industries may be at a slightly increased risk of beryllium exposure 

due to contact with beryllium-contaminated dust within the household, as opposed to ambient air levels. 

Occupationally exposed workers who carry beryllium dust on their clothes from the workplace to their 

home may increase the risk of beryllium exposure to their family members (EPA 1987). However, it is 

common today for beryllium industries to provide and launder employee's work clothes. The National 

Emission Standard for Hazardous Air Pollutants (NESHAPS) restricts the amount of beryllium emitted 

into the environment by industries that process beryllium ores, metals, oxides, alloys, or wastes. The 

NESHAPS can be met by complying with either a 10 g per 24-hour emission limit or by meeting an 

ambient air concentration of 0.01 μg/m3

 of air averaged over a 30-day period (EPA 1982). Machine 

shops machining alloys containing #5% beryllium by weight are excluded from regulation under the 

NESHAPS emission standard (see 40 CFR Part 61, subpart C 61.30(b) 2001). No new cases of beryllium 

disease in people living near beryllium-processing industries have been reported in the past several years, 

probably because the past exposures were relatively high compared to present levels of beryllium in the 

ambient and workplace air (EPA 1987; NIOSH 1995). 

Individuals may be exposed to high levels of beryllium from implanted dental prostheses (EPA 1987). 

The highest concentration of beryllium released from base metal alloy used as dental crowns measured in 

an artificial oral environment was 8 μg/day per crown (Tai et al. 1992). The mantles of some lanterns 

used by campers contain approximately 600 μg of beryllium, and most of the beryllium becomes airborne 

during the first 15 minutes when a new mantle is used (Fishbein 1981). Therefore, people who camp 

outdoors and use these mantles are possibly exposed to higher than normal levels of beryllium. A small 

percentage of the population is sensitive to very low concentrations of beryllium, but there is no evidence 

that sensitivity develops at beryllium concentrations present in food or water, or that sensitivity is 

aggravated by ingestion of beryllium. No other special groups at risk were identified (EPA 1980). 
 

 

BERYLLIUM 178 

6. POTENTIAL FOR HUMAN EXPOSURE 

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 

adequate information on the health effects of beryllium 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 beryllium. 

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 relevant physical and chemical properties of beryllium are 

known (see Section 4.2). Additional information regarding the chemical forms of beryllium in coal fly 

ash and aerosols produced by specific industrial processes, and the mode by which beryllium compounds 

are incorporated into biological systems would be useful. Additional information about the chelation of 

beryllium (especially about chelating agents that may be used in the development of beryllium-specific 

chelation therapy) would also be useful. 

Production, Import/Export, Use, Release, and Disposal. Data regarding the production, 

import/export, and use of beryllium and beryllium compounds are available (see Sections 5.1 through 

5.3). According to the Emergency Planning and Community Right-to-Know Act of 1986, 42 U.S.C. 

Section 11023, industries are required to submit chemical release and off-site transfer information to the 

EPA. The TRI is updated yearly and provides a list of industrial production facilities and emissions. 

As reported in Tables 6-2 and 6-3, the most significant amount of beryllium and beryllium compounds 

from production and use facilities is disposed of on land. Little is known about the methods used for land 

disposal of beryllium, except that small amounts of beryllium waste are discharged into public sewers 
 

 

 

 

BERYLLIUM 179 

6. POTENTIAL FOR HUMAN EXPOSURE 

(TRI99 2002). Additional data examining the method used for land disposal of beryllium waste and the 

routes by which beryllium might find its way from land disposal sites into groundwater would be useful. 

Environmental Fate. For solids, there is a need to determine uptake factors into edible portions of 

plants and not just adherence to the root structure. Dry or wet deposition from the atmosphere to soil and 

water can occur. Little experimental data on the particle size and residence time of beryllium and 

beryllium compounds present in the ambient atmosphere are available. Additional data examining the 

possible chemical transformation reactions of beryllium and its half-life in air would be useful. Data 

regarding the dominant types of sorption mechanisms for beryllium (e.g., ion exchange vs. chemical 

sorption) for different mineral and environmental conditions are limited. Additional information 

elucidating the fate of beryllium with respect to its chemical speciation in soil is necessary. 

Bioavailability from Environmental Media. Although the absorption of specific beryllium 

compounds from skin contact, inhalation, and ingestion have been studied in animals (see Section 3.3.1), 

the bioavailability of beryllium or its compounds from contaminated air, water, soil, or plant material may 

differ significantly from the studied values. Additional information on the dependence of absorption of 

beryllium on such parameters as chemical form, extent of sorption in the host medium, and other possible 

variables would be useful. 

Food Chain Bioaccumulation. Beryllium does not bioconcentrate to high levels in aquatic animals 

(EPA 1980), although the bioconcentration in bottom-dwelling animals may be higher than non bottomdwelling animals (Byrne and DeLeon 1986). There is no evidence of biomagnification of beryllium 

within terrestrial or aquatic food chains (Fishbein 1981). Further studies establishing the 

biomagnification potential for beryllium would be useful. Data regarding the intake of beryllium from 

food are lacking (Vaessen and Szteke 2000; Wolnik et al. 1984). The accuracy of the available database 

of beryllium in foods is questionable (Vaessen and Szteke 2000). More reliable concentration 

information is needed on levels of beryllium in food stuff to reduce or eliminate the uncertainties in 

estimating the dietary intake of beryllium (Vaessen and Szteke 2000). Such information would be 

important in assessing the contribution of food to the total intake of beryllium from different pathways. 

Exposure Levels in Environmental Media. Some data on the levels of beryllium in air and 

drinking water are available. Limited data regarding the ambient concentration of beryllium near 

beryllium-containing hazardous waste sites in the United States are available. These monitoring data are 

important for assessing the potential health risk for individuals living near the waste sites (Eckel and 
 

 

 

BERYLLIUM 180 

6. POTENTIAL FOR HUMAN EXPOSURE 

Langley 1988). Nationwide monitoring data determining the levels of beryllium in U.S. drinking water at 

a detection limit <10 ng/L would be useful. Reliable and more recent monitoring data for the levels of 

beryllium in air, drinking water, soil (particularly at NPL sites), and food would be useful in estimating 

exposure from each source. Remedial investigations and feasibility studies conducted at the NPL sites 

contaminated with beryllium will add to the available database on exposure levels in environmental 

media. Investigations at these sites will also increase the current knowledge regarding the transport and 

transformation of beryllium at hazardous waste sites. 

Exposure Levels in Humans. Beryllium levels in the urine and lung of both the control and 

occupationally exposed populations are available (Kanarek et al. 1973; Stiefel et al. 1980). No data on 

the beryllium levels in body tissues or fluids of populations living near hazardous waste sites or coal-fired 

power plants are available. Such information would be useful in assessing exposure levels for this 

population. Further studies regarding the possibility of increased exposure to beryllium via dental 

implants may be useful. 

Exposures of Children. Children will be exposed to beryllium in the same manner as adults in the 

general population (i.e., ingestion of food and water, and inhalation of air). 

Child health data needs relating to susceptibility are discussed in Section 3.12.2 Identification of Data 

Needs: Children’s Susceptibility. 

Exposure Registries. The Beryllium Case Registry (BCR) was established at Massachusetts General 

Hospital, Boston, Massachusetts in 1952 and taken over by NIOSH in the late 1970s. Since its transfer to 

NIOSH, no additional cases were added. Presently, the BCR is not an active registry. This element is not 

currently one of the compounds for which a subregistry has been established in the National Exposure 

Registry. The element 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 the exposure to 

this element. 
BERYLLIUM 181 

6. POTENTIAL FOR HUMAN EXPOSURE 

6.8.2 Ongoing Studies 

The Federal Research in Progress (FEDRIP 2001) 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. These 

studies are summarized in Table 6-8. 
BERYLLIUM	 182 

6. POTENTIAL FOR HUMAN EXPOSURE 

Table 6-8. Ongoing Studies on Human Exposure to Beryllium 

Investigator Affiliation Subject	 Sponsor 

Peters, EL Chicago State	 Fluctuating asymmetry in National Institute of 

University	 isopods as indicator of General Medical 

hazardous metals in urban Sciences 

area 

Grew, ES University of Maine	 Beryllium in antarctic NSF 

ultrahigh-temperature 

granulite-facies rocks and 

its role in partial melting of 

the lower continental crust 

Source: FEDRIP 2001 

NSF = National Science Foundation 
BERYLLIUM 183 

7. ANALYTICAL METHODS 

The purpose of this chapter is to describe the analytical methods that are available for detecting, 

measuring, and/or monitoring beryllium, its metabolites, and other biomarkers of exposure and effect to 

beryllium. 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. 

7.1 BIOLOGICAL MATERIALS 

Methods used for the analysis of beryllium in biological materials are reported in Table 7-1. Reviews of 

beryllium analysis methods in biological media have been published (Delves 1981; Tsalev and Zaprianov 

1984). Although the level of beryllium in urine may be informative of the current exposure level, it is not 

useful for quantitative exposure analysis. In contrast, the level of beryllium in blood, serum, or plasma is 

predictive of the intensity of current exposure from certain beryllium compounds (Tsalev and Zaprianov 

1984; see Section 3.4.2). Neither flame atomic absorption spectroscopy (AAS) nor atomic emission 

spectroscopy (AES) have adequate sensitivity for measuring beryllium concentrations found in body 

fluids and tissues. The determination of beryllium levels in these matrices using the preceding techniques 

requires elimination of spectral interferences. Graphite furnace (or electrothermal) atomic absorption 

spectroscopy with background correction (deuterium or Zeeman effect) and inductively coupled plasma 

atomic emission spectroscopy (ICP-AES) are common analytical methods for beryllium. These 

techniques have the sensitivity and accuracy to determine the content of beryllium in body fluids and 

tissues (Delves 1981). To avoid sample contamination, stainless steel needles should be avoided for the 

collection of whole blood samples. Certain polyethylene sample collection tubes with added heparin as 

an anticoagulant may contaminate whole blood samples (Paudyn et al. 1989). A gas chromatographic 

method to detect beryllium in whole blood down to a concentration level of 0.02 μg/mL is available 

(Taylor and Arnold 1971). Krachler et al. (1999b) measured beryllium in umbilical cord serum, 

colostrum, and maternal serum at concentrations to <1 μg/L using inductively coupled plasma mass 
Table 7-1. Analytical Methods for Determining Beryllium in Biological Materia

Analytical method Sample detection 

Sample matrix Preparation method limit Percent recovery 

Blood Add EDTA; acidify GC/EC ~20 μg/L 44–117% 

Blood (dog) Add sodium hydroxide; 

dissolve by heating; chelate with tri-fluoroacetylacetone; extract with benzene 

GC/EC No data 95–117% 

Urine Dilute with nitric acid ICP-MS 0.1 μg/L No data 

Urine Acidified urine precipitated 

with excess ammonium hydroxide; centrifuge, dissolve in nitric acid and add lanthanum 

GFAAS 0.01 μg/L 94–110% 

Urine Dilute with a matrix modifier GFAAS 0.05 μg/L 107%; 94–98% Urine (human and rat) 

Add EDTA to aqueous sample; adjust to pH 6; add trifluoroacetylacetone in benzene; extract 

GC/EC 1 μg/L 68–123% 

Feces Digest; dry ash; dissolve 

residue in acid 

GFAAS 1 μg/kg; ~2 μg/kg 108%; 90–110% 

Fingernails Acid digestion; dry ash; 

dissolve in acid 

GFAAS ~2 μg/kg 90–110% 

Hair-fingernails Dissolve in nitric acidperchloric acid (1:1) GFAAS <1 μg/kg 98–105% 
Table 7-1. Analytical Methods for Determining Beryllium in Biological Materials (con

Analytical method Sample detection 

Sample matrix Preparation method limit Percent recovery 

Liver (bovine) Wet-ash tissue in a mixture of Fluorescence No data No data 

acids; chelate with spectroscopy acetylacteone; extract (chloroform); acidify chelate with 2-hydroxy-3-naphthoic acid reagent 

Lung tissue Sample subjected to dry or wet ICP-AES 0.075 mg/kg No data 

ashing 

Lung tissue Dry; acid digestion; dilute in GFAAS No data No data 

acid; standard addition 

EDTA = ethylenediaminetetraacetic acid; GC/EC = gas chromatography-electron capture; GFAAS = graphite furnace atomic absorption 

inductively coupled plasma-atomic emission spectrometry; ICP-MS = inductively coupled plasma-mass spectrometry 
BERYLLIUM 186 

7. ANALYTICAL METHODS 

spectroscopy (ICP-MS). Another relative method for the detection of beryllium is Laser Ion Mass 

Analysis (LIMA). This analysis method uses a laser beam to ionize elements (e.g., beryllium) in a small 

section of tissue and detects the elements by time-of-flight mass spectrometry (MS) (Williams and 

Kelland 1986). 

Standard reference materials (SRMs) are useful to determine the accuracy of an analytical method. A 

standard reference urine (SRM=2,670) with a certified beryllium concentration is available from National 

Institute of Standards and Technology (Shan et al. 1989). 

7.2 ENVIRONMENTAL SAMPLES 

Methods used to analyze beryllium in environmental media are presented in Table 7-2. The standard test 

methods approved by EPA and NIOSH for beryllium analysis in ambient and occupational samples are 

included in Table 7-2. Environmental samples analyzed by atomic absorption spectroscopy and gas 

chromatography (GC) require pretreatment to remove interfering substances and increase sensitivity 

(EPA 1987). At high concentrations (500 mg/kg), aluminum and silicon interfere with the analysis of 

beryllium by atomic absorption spectroscopy. Separation of these elements is achieved by chelation and 

extraction with an organic solvent. High concentrations of iron interfere with the 243.86 nm beryllium 

emission line used in ICP-AES (Vaessen and Szteke 2000). A method using laser spark spectroscopy has 

been used for the direct determination of trace quantities of airborne beryllium collected on filters 

(Cremers and Radziemski 1985). A recent analytical advance is laser induced breakdown spectroscopy 

(LIBS), a real time technique (Langner et al. 1997). This technique has been used to monitor worker 

exposure to beryllium in 30-second sample intervals (Langner et al. 1997). 

The following SRMs for beryllium in environmental samples are available from the National Institute of 

Standards and Technology: San Joaquin soil, SRM=2,709; Montana soil 1, SRM=2,710; Montana soil 

2, SRM=2,711; coal, SRM=1,632; fly ash, SRM=1,633; trace elements in water, SRM=1,643; orchard 

leaves, SRM=1,571; and filter media, SRM=2,676 (Chang et al. 1982; Epstein et al. 1978; Gladney and 

Owens 1976; Namiesnik and Zygmunt 1999). SRMs are available for beryllium in soils and sediments 

from Canadian Certified Reference Materials Project (CCRMP), National Research Council of Canada 
Table 7-2. Analytical Methods for Determining Beryllium in Environmental Samp

Sample detection Percent 

Sample matrix Preparation method Analytical method limit recovery 

Air Air Air Occupational air Occupational air Occupational air Water Water Water 

Wet ash collection filter with 

mixture of HNO3/HCl mixture; 

concentrate; add HNO3/LiCl 

solution 

Dissolve collection filter matrix 

in HF; add HNO3; water; boil; 

dilute 

None 

Dry collection filter; add HNO3 

and sulfuric acid; solubilize with concentrated HCI 

Filter collection, acid digestion Filter collection, acid digestion 

Acidify with HNO3; evaporate 

under heat; add HCl or HNO3 

Acidify with HNO3 

Digest; acidify; dilute 

Optical emission spectroscopy GFAAS FAAS 

Laser spark technique 

Direct current plasma AES 

GFAAS (method 7102) 

GFAAS (method 7300) 

AAS (aspirationmethod 210.1) AAS (furnace method 210.2) GFAES GFAAS 

ICP-AES (method 

3500-BE-C); ICP-AES (method D1976) 

5.3 μg/L (in dissolved particles) 0.05ng/m3 

2.5 ng/m3 

0.45 ng/cm-2 

0.0036 μg/sample 

5 pg/sample 1 pg/sample 

0.005 mg/L 0.2 μg/L 2 μg/L 0.06 μg/L 1 μg/L No data 

96–108% No data No data 

100% 

107% 

No data 

97–100% No data 112% (average) 98% (average) No data No data 
Table 7-2. Analytical Methods for Determining Beryllium in Environmental Samples (c

Sample detection Percent 

Sample matrix Preparation method Analytical method limit recovery 

Water Digest; acidify; dilute ICP-MS (method 0.1 μg/L No data 

933.14) 

Seawater Add specific volumes of EDTA, GC/EC 0.02 ng/L 93–104% 

sodium acetate, benzene and Hfta to collected seawater; rinse organic phase with NaOH; UV oxidize 

Sediment Extract dry sample with HCI DCP-AES 0.02 μg/g No data 

solution 

Soil and Acid digest in bomb; dilute ICP-AES (method No data No data 

sediment D1971-A) Soil, sludge, Acid digestion of sample ICP-AES (method 0.3 μg/L 97.7–100% 

sediments, and 6010) other solid wastes Solid (coal ash) Acid digest in bomb; dilute with GFAAS 0.14–4.8 μg/L No data 

acid 

Oils and waxes Add potassium permanganate FAAS or ICP-AES No data No data 

with heat; acidify; digest with (method 3031) heat; filter; dilute 
Table 7-2. Analytical Methods for Determining Beryllium in Environmental Samples (c

Sample matrix Food 

Preparation method 

Dissolve in HNO3; dry, then treat 

with HCl-HClO4 and heat; filter 

Analytical method 

ICP-AES 

Sample detection limit 

No data 

Percent recovery 

No data 

Food Freeze-dry or blender-grind food 

composites; solubilize with

ICP-AES 2.5 μg/kg No data 

HNO 3, HClO4, H2SO4, or HCl 2 μg/kg 98% 

AAS = atomic absorption spectrometry; AES = atomic emission spectrometry; AOAC = Association of Official Analytical Chemists; APHHealth Association; ASTM = American Society for Testing and Materials; DCP-AES = direct current plasma-atomic absorption spectrosEDTA = ethylenediamine tetraacetic acid; FAAS = flame atomic absorption spectrometry; GC/EC = gas chromatography-electron captu

furnace atomic absorption spectrometry; GFAES = graphite furnace atomic emission spectrometry; HCI = hydrochloric acid; HClO4 = pe

HF = hydrogen fluoride; Hfta = 1,1,1-trifluoro-2,4-pentanedione; HNO3 = nitric acid; H2SO4 = sulfuric acid; ICP-AES = inductively couple

emission spectrometry; ICP-MS = inductively coupled plasma-mass spectrometry; LiCl = lithium chloride; NaOH = sodium hydroxide; Nfor Occupational Safety and Health; OSW = Office of Solid Waste of the U.S. Environmental Protection Agency; UV = ultraviolet 
 

BERYLLIUM 190 

7. ANALYTICAL METHODS 

NRCC and the U.S. Geological Survey (USGS): soil, SO 1; soil-sandy, SO 2; soil-limestone til, SO 3; 

soil-silty, SO 4; arable soil, TILL 2; Lake sediment, IKSD 4; sediment MESS-1; sediment BCSS-1; and 

marine sediment, MAG 1 (Namiesnik and Zygmunt 1999; Waldichuk et al. 1987). 

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 beryllium 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 beryllium. 

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. 

Exposure. As discussed in Section 3.8.1, the beryllium level in blood/serum/plasma is an accurate 

biomarker of exposure to certain forms of beryllium (James and Williams 1985; Stokes and Rossman 

1991; Zorn et al. 1986). The level of beryllium in normal blood is 1 μg/kg (Zorn et al. 1986). No 

analytical method capable of determining beryllium in blood at or below this level has been reported in 

the literature. The routine analytical methods presently available are useful for detecting beryllium levels 

in the blood of occupationally exposed persons. 

Effect. There are several methods for measuring effects due to beryllium exposure (see Section 3.8.2). 

An antigen-specific lymphocyte proliferation test confirms exposure and may be useful in early diagnosis 

of individuals with chronic beryllium disease; several methods for the lymphocyte proliferation test have 

been reported (Bobka et al. 1997; Kreiss et al. 1989; Mroz et al. 1991; Rossman et al. 1988; Stokes and 
 

BERYLLIUM 191 

7. ANALYTICAL METHODS 

Rossman 1991). Another method that can be used for the positive diagnosis of chronic beryllium disease 

when other symptoms are evident is LIMA of histological sections of lung or skin granulomas. LIMA 

can detect parts per million (or mg/kg) levels of beryllium in these tissues (Williams and Kelland 1986). 

Methods for Determining Parent Compounds and Degradation Products in Environmental 

Media. The concentration of beryllium in approximately 95% of drinking waters in the United States is 

<0.01 μg/L (EPA 1980; Iwan 1987). Although a few methods are available (see Table 7-2) to detect 

beryllium at such low concentrations, no routine methods are available to quantify beryllium 

concentrations in most U.S. drinking waters. Similarly, the detection limit for beryllium in fresh 

vegetables by the commonly used analytical method (see Table 7-2) is 2.5 μg/kg.

 At this detection limit, 

beryllium was not found in two foods tested (Wolnik et al. 1984). Developing a routine analytical 

method to detect low levels of beryllium in foods would be useful. The data on the levels of beryllium in 

drinking water and total diet samples from ambient sources are significant in determining background 

levels of daily intake from these routes. 

7.3.2 Ongoing Studies 

The FEDRIP database lists an ongoing National Institute of Environmental Health and Sciences study by 

Jolly et al. at ELS Technology, Inc. (Lakewood, Colorado) that is investigating a portable low-cost 

analyzer for the detection of beryllium in toxic metal aerosols (FEDRIP 2001). 
BERYLLIUM 192 
BERYLLIUM 193 

8. REGULATIONS AND ADVISORIES 

8. REGULATIONS AND ADVISORIES 

A chronic-duration oral MRL of 0.002 mg beryllium/kg/day was derived for beryllium. This MRL is 

based on a benchmark dose (defined as the 95% lower confidence limit of the dose corresponding to a 

10% increase in the incidence of small intestine lesions compared to controls) of 0.56 mg 

beryllium/kg/day. The benchmark dose was divided by an uncertainty factor of 100 (10 for extrapolation 

from animals to humans and 10 for intrahuman variability) and a modifying factor of 3 (to account for the 

lack of a study that supports the gastrointestinal effects found in the Morgareidge et al. [1976] dog study 

and the uncertainty as to whether the benchmark dose level is the NOAEL). 

A chronic oral reference dose (RfD) of 0.002 mg beryllium/kg/day has been derived and verified by EPA 

for beryllium (IRIS 2002). The RfD is based on a benchmark dose of 0.46 mg beryllium/kg/day for small 

intestine lesions in dogs exposed to beryllium sulfate in the diet for 33–172 weeks (Morgareidge et al. 

1976). This benchmark concentration was divided by an uncertainty factor of 300 to account for 

extrapolation from animals to humans (10), human variability (10), and database gaps (3), particularly 

adequate reproductive and developmental toxicity studies and studies examining immunological end 

points. The chronic-duration oral MRL and the RfD were both derived using a benchmark analysis and 

the same incidence data set. The difference in the benchmark doses is due to the differences in the 

mathematical model fit to the incidence data (ATSDR used a probit model with a chi-square goodness-offit statistic p-value of 0.9999 and EPA used a weibull model with a chi-square goodness of fit statistic 

p-value of 0.96) and the higher number of significant figures that EPA used to express beryllium doses. 

A chronic inhalation reference concentration (RfC) of 0.02 μg/m3

 has been derived for beryllium (IRIS 

2000). The RfC is based on two human studies finding chronic beryllium disease in workers at a facility 

manufacturing beryllia ceramics (Kreiss et al. 1996) and in residents living near a beryllium 

manufacturing facility (Eisenbud et al. 1949). The Kreiss et al. (1996) study identified a LOAEL of 

0.55 μg/m3

 for beryllium sensitization and subclinical chronic beryllium disease, and the Eisenbud et al. 

(1949) study identified a NOAEL of 0.01–0.1 μg/m3

 for chronic beryllium disease. The LOAEL 

identified in the Kreiss et al. (1996) study was used for the operational derivation of the RfC. This 

LOAEL was divided by an uncertainty of 10 to account for less-than-chronic exposure duration (1), use 

of a LOAEL (3), human variability (1), and database limitations (3), particularly the poor quality of 

exposure monitoring in the co-principal studies and other epidemiology studies. 
BERYLLIUM 194 

8. REGULATIONS AND ADVISORIES 

NTP (1999, 2002) lists beryllium and certain beryllium compounds (beryllium-aluminum alloy, beryllium 

chloride, beryllium fluoride, beryllium hydroxide, beryllium oxide, beryllium phosphate, beryllium 

sulfate, beryllium zinc silicate, and beryl ore) as substances reasonably anticipated to be carcinogens. 

IARC (2001) has classified beryllium and beryllium compounds in Group 1, carcinogenic to humans, and 

EPA classifies inhaled beryllium in Group B1, a probable human carcinogen (IRIS 2002). 

The international, national, and state regulations and guidelines regarding beryllium in air, water, and 

other media are summarized in Table 8-1. 
BERYLLIUM	 195 

8. REGULATIONS AND ADVISORIES 

Table 8-1. Regulations and Guidelines Applicable to Beryllium 

Agency	 Description Information Reference 

INTERNATIONAL 

Guidelines: 

IARC	 Carcinogenicity classification— 

beryllium and beryllium 

compounds 

NATIONAL 

Regulations and 

Guidelines: 

a. Air 

ACGIH Beryllium and compounds (as Be) 

TLV (8-hour TWA) 

STEL (15-minute TWA) 

DOD	 Requires notification to the EPA 

when conducting operations, 

construction, or modification of a 

source of hazardous air 

pollutants—beryllium 

EPA	 National emission standards for 

hazardous air pollutants— 

beryllium emissions to the 

atmosphere from rocket-motor test 

sites 

National emission standards for 

hazardous air pollutants—if 

combustion products from the 

firing of beryllium propellant are 

collected in a closed tank 

National emission standards for 

hazardous air pollutants 

Beryllium emissions to the 

atmosphere from stationary 

sources 

Request approval from the 

Administrator to meet an 

ambient concentration limit on 

beryllium in the vicinity of the 

stationary source 

Group 1a IARC 2001 

ACGIH 2001 

0.002 mg/m3 

0.01 mg/m3 

DOD 2001 

32CFR650.132 

Shall not exceed EPA 2001i 

75 μg minutes/m3

 of 40CFR61.42 

air within the limits of 

10–60 minutes, 

accummulated during 

any 2 consecutive 

weeks, in any area in 

which an effect 

adverse to public 

health could occur 

Emissions from such EPA 2001i 

tank shall not exceed 40CFR61.42 

2 g/hour and a 

maximum of 10 g/day 

EPA 2001l 

40CFR61.32 

Shall not exceed 

10 grams over a 

24-hour period 

0.01 μg/m3

, averaged 

over a 30-day period 
BERYLLIUM 196 

8. REGULATIONS AND ADVISORIES 

Table 8-1. Regulations and Guidelines Applicable to Beryllium (continued) 

Agency Description Information Reference 

NATIONAL (cont.) 

NIOSH Beryllium and beryllium 

compounds (as Be) 

REL (10-hour TWA)b 

IDLH 

5x10-4 mg/m3 

4 mg/m3 

NIOSH 2001 

OSHA PEL (8-hour TWA)—beryllium and 

beryllium compounds (as Be) 

2 μg/m3 OSHA 2001a 

29CFR1910.1000 

Table Z-1 

Acceptable ceiling 

concentration—beryllium and 

beryllium compounds 

5 μg/m3 OSHA 2001a 

29CFR1910.1000 

Table Z-2 

Acceptable maximum peak above 

the acceptable ceiling 

concentration for an 8-hour shift 

25 μg/m3 OSHA 2001a 

29CFR1910.1000 

Table Z-2 

for a maximum duration of 

30 minutes—beryllium and 

beryllium compounds 

PEL (8-hour TWA) for construction 

workers—beryllium and beryllium 

compounds (as Be) 

2 μg/m3 OSHA 2001c 

29CFR1926.55 

PEL (8-hour TWA) for shipyard 

workers—beryllium and beryllium 

compounds (as Be) 

2 μg/m3 OSHA 2001b 

29CFR1915.1000 

Welding or cutting indoors, 

outdoors, or in confined spaces 

involving beryllium-containing 

base or filler metals shall be done 

OSHA 2001d 

29CFR1910.252 

(c)(8) 

using local exhaust ventilation and 

airline respirators 

USC Listed as a hazardous air USC 2001 

pollutant—beryllium compounds 42 USC 7412 

b. Water 

EPA Groundwater monitoring— 

beryllium (total) 

Suggested methods 

6010 

7090 

7091 

PQL 

3 μg/L 

50 μg/L 

2 μg/L 

EPA 2001b 

40CFR264, 

Appendix IX 
BERYLLIUM 197 

8. REGULATIONS AND ADVISORIES 

Table 8-1. Regulations and Guidelines Applicable to Beryllium (continued) 

Agency Description Information Reference 

NATIONAL (cont.) 

EPA Land disposal restrictions; 

universal treatment standards for 

beryllium 

Wastewater standard 

Non-wastewater standard 

0.82 mg/L2 

1.22 mg/L TCLP 

EPA 2001e 

40CFR268.48 

MCLG—beryllium 0.004 mg/L EPA 2001g 

40CFR141.51(b) 

MCL—beryllium 0.004 mg/L EPA 2001f 

40CFR141.62(b) 

National recommended water 

quality criteria for human health for 

consumption of beryllium 

Water and organism 

Organism only 

EPA has not 

calculated human 

health criteria for this 

contaminant 

EPA 1999a 

Health Advisories for beryllium 

10-kg child 

1-day 

10-day 

DWELc 

30 mg/L 

30 mg/L 

0.07 mg/L 

EPA 2000a 

c. Food 

FDA Bottled water allowable limit— 

beryllium 

0.004 mg/L FDA 2001 

21CFR165.110 

d. Other 

ACGIH Carcinogenicity classification— 

beryllium and compounds 

A1d ACGIH 2001 

DOE Chronic beryllium disease 

prevention program 

DOE 2001 

10CFR850 

EPA Beryllium and compounds 

Carcinogenicity classification 

RfC 

RfD 

B1e 

2X10-2 μg/m3 

2x10-3 mg/kg/day 

IRIS 2001 

Health based limits for exclusion 

of waste-derived residue— 

beryllium 

TCLP extract concentration 

limits 

7x10-3 mg/L 

EPA 2001c 

40CFR266, 

Appendix VII 
BERYLLIUM 198 

8. REGULATIONS AND ADVISORIES 

Table 8-1. Regulations and Guidelines Applicable to Beryllium (continued) 

Agency Description Information Reference 

NATIONAL (cont.) 

EPA Identification and listing of 

beryllium powder as a hazardous 

waste—hazardous waste number 

P015 EPA 2001d 

40CFR261.33(e) 

Reportable quantity regarded as a 

CERCLA hazardous substance 

under Section 307(a) of the Clean 

Water Act 

Beryllium and compounds 

Beryllium chloride, beryllium 

fluoride, and beryllium nitrate 

1 pound 

5,000 pounds 

EPA 2001a 

40CFR302.4 

Standards for management of 

hazardous waste 

Unit risk 

Risk specific doses 

2.4x10-3 μg/m3 

4.2x10-3 μg/m3 

EPA 2001j 

40CFR266, 

Appendix V 

Toxic chemical release reporting; 

community right-to-know, effective 

date for reporting—beryllium 

01/01/87 EPA 2001k 

40CFR372.65 

Toxic pollutant designated 

pursuant to Section 307(a)(1) of 

the Clean Water Act—beryllium 

and compounds 

EPA 2001l 

40CFR401.15

 NTP Carcinogenicity classificationberyllium and compounds Known human 

carcinogens 

NTP 1999, 2002 

STATE 

Regulations and 

Guidelines: 

a. Air 

North Carolina Toxic air pollutant—beryllium 

Chronic toxicant (24 hours) 4.1x10-6 mg/m3 

BNA 2001 

Vermont Hazardous ambient air 

standardf

—beryllium, total 

1.3x10-3 μg/m3 VT Agency of 

Natural 

Resources 1998 

Washington Acceptable source impact levels 

(at 10-6 risk), annual average— 

beryllium and compounds 

4.2x10-4 μg/m3 WA Dept. of 

Ecology 1998 

Wisconsin Hazardous air contaminants 

without acceptable ambient 

concentrations requiring 

application of best available 

control technology—beryllium and 

beryllium compounds (as Be) 

25 pounds/year2 WI Dept. of 

Natural 

Resources 1997 
BERYLLIUM	 199 

8. REGULATIONS AND ADVISORIES 

Table 8-1. Regulations and Guidelines Applicable to Beryllium (continued) 

Agency	 Description Information Reference 

STATE (cont.) 

b. Water 

Alaska Primary MCL—beryllium 0.004 mg/L	 AK Dept. of 

Environ. 

Conservation 

1999 

Arizona	 Aquifer water quality standard— 0.004 mg/L BNA 2001
 

beryllium
 

Drinking water guideline— 0.007 μg/L HSDB 2001 

beryllium 

California Primary MCL—beryllium 0.004 mg/L	 CA Dept. of 

Health Services 

2000 

Hawaii MCL—beryllium 0.004 mg/L	 HI Dept. of Health 

1999a 

Toxic pollutant standards— HI Dept. of Health 

beryllium 1999b 

Freshwater 

Acute 43 mg/L 

Chronic No standard 

Saltwater 

Acute No standard 

Chronic No standard 

Fish Consumption	 0.038 mg/L 

Kansas	 Water quality standards— KS Dept. of
 

beryllium, total Health and
 

Aquatic life 130 mg/L Environ. 1999 

Acute 5.3 mg/L 

Chronic 

Public health 0.13 mg/L 

Food procurement 4.0 mg/L 

Domestic water supply 

Kentucky	 Domestic water supply use— 0.04 μg/L BNA 2001
 

beryllium concentration
 

Minnesota	 Drinking water guideline— 0.08 μg/L HSDB 2001
 

beryllium
 

New Jersey Groundwater standards—	 NJ Dept. of 

beryllium Environ. 

Groundwater quality criteria 0.008 μg/L Protection 1993 

PQL 20 μg/L 
BERYLLIUM 200 

8. REGULATIONS AND ADVISORIES 

Table 8-1. Regulations and Guidelines Applicable to Beryllium (continued) 

Agency Description Information Reference 

STATE (cont.) 

Rhode Island Beryllium 

Groundwater quality standard 

Preventive action limit 

0.004 mg/L 

0.002 mg/L 

BNA 2001 

South Dakota MCL for community and nontransient non-community water 

systems—beryllium 

0.004 mg/L SD Dept. of 

Environ. & Natural 

Resources 1998 

Vermont Groundwater quality standard— 

beryllium 

Enforcement standard 

Preventive action level 

4.0 μgL 

1.0 μg/L 

BNA 2001 

c. Food No data 

d. Other 

Connecticut Direct exposure criteria for soil— 

beryllium 

Residential criteria 

Industrial/commercial criteria 

2 mg/kg 

2 mg/kg 

BNA 2001 

Massachusetts Human health-based toxicity 

values—beryllium 

Chronic oral RfD 

Oral cancer slope factor 

2.0x10-3 mg/kg/day 

4.3 (mg/kg/day)-1 

BNA 2001 

Minnesota Health risk limits 

Slope factor 

Health risk limit 

4.3 (mg/kg/day)-1 

0.08 μg/L 

BNA 2001 

a

Group 1: carcinogenic to humans

b

Potential occupational carcinogen 

c

DWEL: A lifetime exposure concentration protective of adverse, non-cancer health effects that assumes all of the 

exposure to a contaminant is from a drinking water source. d

A1: confirmed human carcinogen. The agent is carcinogenic to humans based on the weight of evidence from 

epidemiologic studies.

E

B1: probable human carcinogen

f

Indicates value derived using an inhalation cancer potency factor 

ACGIH = American Conference of Governmental Industrial Hygienists; BNA = Bureau of National Affairs; 

CERCLA = Comprehensive Environmental Response Compensation and Liability Act; CFR = Code of Federal 

Regulations; DOD = Department of Defense; DOE = Department of Energy; DWEL = drinking water equivalent 

level; EPA = Environmental Protection Agency; FDA = Food and Drug Administration; HSDB = Hazardous 

Substances Data Bank; IARC = International Agency for Research on Cancer; IDLH = immediately dangerous to 

life or health; IRIS = Integrated Risk Information System; MCL = maximum contaminant level; MCLG = maximum 

contaminant level goal; NIOSH = National Institute for Occupational Safety and Health; OSHA = Occupational 

Safety and Health Administration; PEL = permissible exposure level; PQL = practical quantitation limits; 

REL = recommended exposure limit; RfC = inhalation reference concentration; RfD = oral reference dose; 

STEL = short-term exposure limit; TCLP = toxicity characteristic leaching procedure; TLV = threshold limit value; 

TWA = time-weighted average; USC = United States Code 
BERYLLIUM 201 

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BERYLLIUM 241 

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 a 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 which 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. 
BERYLLIUM 242 

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 which 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. 
BERYLLIUM 243 

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 which 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 which 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. 
BERYLLIUM 244 

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. 

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 whereby the 

physiologically-based model compartments represent real anatomic regions of the body. 

Physiologically Based Pharmacodynamic (PBPD) Model—A type of physiologically-based doseresponse model which quantitatively describes the relationship between target tissue dose and toxic end 

points. These models advance the importance of physiologically based models in that they clearly 
BERYLLIUM 245 

10. GLOSSARY 

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. 
BERYLLIUM 246 

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 min 

continually. No more than four excursions are allowed per day, and there must be at least 60 min 

between exposure periods. The daily Threshold Limit Value - Time Weighted Average (TLV-TWA) may 

not be exceeded. 

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 lowestobserved-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 one can be used; 

however a reduced UF of three may be used on a case-by-case basis, three being the approximate 

logarithmic average of 10 and 1. 
BERYLLIUM 247 

10. GLOSSARY 

Xenobiotic—Any chemical that is foreign to the biological system. 

BERYLLIUM A-1 

APPENDIX A
 

ATSDR MINIMAL RISK LEVEL 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. 
BERYLLIUM 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 a hundredfold 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 agencywide 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, Mailstop E-29, Atlanta, Georgia 30333. 
BERYLLIUM A-3 

APPENDIX A 

MRL WORKSHEET 

Chemical Name: Beryllium and Compounds 

CAS Number: 

Date: May 16, 2002 

Profile Status: Third Post Public Comment Draft 

Route: [ ] Inhalation [X] Oral 

Duration: [ ] Acute [ ] Intermediate [X] Chronic 

Key to Figure: 11 

Species: Dogs 

Minimal Risk Level: 0.002 [X] mg beryllium/kg/day [ ] ppm 

Reference: Morgareidge K, Cox GE, Gallo MA. 1976. Chronic feeding studies with beryllium in dogs. 

Food and Drug Research Laboratories, Inc. Submitted to the Aluminum Company of America. Alcan 

Research and Development, Ltd., Kawecki-Berylco Industries, Inc., and Brush-Wellman, Inc. 

Experimental design: (human study details or strain, number of animals per exposure/control groups, sex, 

dose administration details): Groups of five male and five female Beagle dogs were fed a diet containing 

0, 5, 50 or 500 ppm beryllium as beryllium sulfate tetrahydrate (0, 0.1, 1, and 12 mg beryllium/kg/day for 

males and 0, 0.2, 1, and 17 mg beryllium/kg/day for females) for 172 weeks. The basal diet was a 

commercial dog chow (Purina®) moistened with warm water; the dogs were given access to the food for 

1 hour/day. After 33 weeks, a group of five male and five female dogs was added to the study and fed a 

diet containing 1 ppm (0.02 and 0.03 mg beryllium/kg/day for males and females, respectively); duration 

of exposure for this group was 143 weeks. The following parameters were used to assess toxicity: daily 

observations, food consumption, body weight, hematology and serum clinical chemistry (blood samples 

collected after 1, 3, 6, 16, 18, 24, 30, and 36 months of exposure), urinalysis (samples collected after 1, 3, 

6, 18, 24, 30, and 36 months of exposure), organ weights (heart, liver, kidney, brain, spleen, pituitary, 

thyroids, adrenals, and gonads), and histopathology of the spleen, thymus, pancreas, lungs, gonads, 

stomach, small and large intestines, urinary bladder, heart, aorta, muscle, adrenals, thyroids, lymph nodes, 

salivary glands, gallbladder, liver, kidneys, pituitary, brain, spinal cord, skin, mammary gland, bone 

marrow, and eyes. 

Effects noted in study and corresponding doses: Two moribund animals in the 500 ppm group were 

sacrificed during week 26; the remainder of the animals in the 500 ppm group were killed during 

week 33. Overt signs of toxicity in the 500 ppm group included lassitude, weight loss, anorexia, and 

visibly bloody feces. A slight anemia (slight decreases in erythrocyte, hemoglobin, and hematocrit; 

statistical analysis not reported), more apparent in the females than in the males, was observed after 3 and 

6 months of exposure; however, there were no alterations in the bone marrow and none of the animals 

was seriously affected. The study authors noted that the anemia may have been related to the 

gastrointestinal tract hemorrhages rather than a direct effect of beryllium on the hematological system. 

All animals in the 500 ppm group showed fairly extensive erosive (ulcerative) and inflammatory lesions 

in the gastrointestinal tract. These occurred predominantly in the small intestine, and to a lesser extent in 

the stomach and large intestine, and were regarded by the authors as treatment-related. All of the animals 

with stomach or large intestinal lesions also had lesions in the small intestine, except for one animal with 

stomach lesions only. This animal had stomach lesions that were very localized and not very severe. 

Erythroid hypoplasia of the bone marrow, bile stasis and vasculitis in the liver, and acute inflammation in 

the lymph nodes were also observed in the 500 ppm group; these effects are likely to be secondary to the 

gastrointestinal hemorrhages and a likely systemic bacterial invasion through the damaged intestinal 

mucosa. 
t

 

BERYLLIUM A-4 

APPENDIX A 

One dog in the 50 ppm group died after 70 weeks. Ulcerative gastrointestinal lesions were observed in 

this animal. No beryllium-related hematological, serum chemistry, urinalysis, organ weight, or body 

weight alterations were observed in the groups exposed to <500 ppm beryllium. 

Dose and end point used for MRL derivation: The chronic-duration oral MRL for beryllium w 

calculated using a benchmark dose method that involves fitting mathemat 

response data for ulcerative lesions of the small intestine of dogs exposed 

diet (Morgareidge et al. 1976). Because there were no apparent sex-related dif 

of these lesions, the incidence data for the male and female dogs were com 

doses for the males and females were averaged. The dose-response data are p 

Dietary Concentration (ppm) Dose (mg beryllium/kg/day) Incidence

0 0 0/10 

1 0.025 0/10 

5 0.15 0/10 

50 1 1/10 

500 14.5 9/10 

For this analysis, the benchmark dose (BMD) was defined as the dose corresp 

the incidence of small intestine lesions compared to controls; the BMDL is 

limit on the BMD. EPA’s BenchMark Dose Software (version 1.3) was used to fit 

models (Gamma, Logistic, Log-Logistic, Multistage, Probit, Log-Probit, Quanta 

Quantal-Quadratic, and Weibull) to the incidence data. Model fit was judge 

associated with the chi-square goodness-of-fit statistic generated by the m 

inspection of the plot of observed and predicted values. The probit model p 

the incidence data; the observed and predicted incidences are illustrated b 

fits the data using the maximum likelihood method and the following equ 

background (1-background) x CumNorm(intercept slope x log(dose)), wher 

cumulative normal distribution function. A BMDL of 0.56 mg beryllium/kg/d 

model. 

[ ] NOAEL [ ] LOAEL [X] Benchmark dose (BMDL) 
 

Probit Model with 0.95 Confidence Level 

Fraction Affected 

1 

0.8 

0.6 

0.4 

0.2 

0 

BMDL BMD 

Probit 

0 2 4 6 8 10 12 14 

 

BERYLLIUM	 A-5 

APPENDIX A 

dose 

22:59 02/05 2002 

Figure 1. Observed and Predicted (by Probit Model) Incidences of Intestinal Lesions in Dogs exposed 

to Beryllium in the Diet. 

Uncertainty Factors used in MRL derivation: 

[X] 10 for use of a extrapolation from animals to humans 

[X] 10 for human variability 

[X]	 3 modifying factor to account for the lack of a study that supports the gastrointestinal effects 

found in the Morgareidge et al. [1976] dog study and the uncertainty as to whether the 

benchmark dose level is the NOAEL. 

Was a conversion factor used from ppm in food or water to a mg/body weight dose? 

Yes. Daily doses were estimated using the estimated TWA body weights of 13.0, 12.7, 13.8, and 12.3 kg 

for males in the 1, 5, 50, and 500 ppm groups, respectively, and 10.2, 10.3, 11.2, and 8.6 kg for females, 

respectively and the reported average food intake of 300 g/day. 

If an inhalation study in animals, list conversion factors used in determining human equivalent dose: 

NA 
 

BERYLLIUM A-6 

APPENDIX A 

Was a conversion used from intermittent to continuous exposure?
 

No
 

Other additional studies or pertinent information that lend support to this MRL:
 

Gastrointestinal effects have not been reported in rats (Morgareidge et al. 1975; Schroeder and Mitchener
 

1976a) or mice (Schroeder and Mitchener 1976b) chronically exposed to dietary beryllium.
 

Agency Contact (Chemical Manager): Cassandra Smith, M.S.
 
BERYLLIUM	 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, 

weight-of-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 they appear within the Discussion of Health Effects by 

Route of Exposure section, by route (inhalation, oral, 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. If data are located in the scientific literature, a table of genotoxicity information is 

included. 

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. 
BERYLLIUM B-2 

APPENDIX B 

Interpretation of Minimal Risk Levels 

Where sufficient toxicologic information is available, we have derived minimal risk levels (MRLs) for 

inhalation and oral routes of entry at each duration of exposure (acute, intermediate, and chronic). These 

MRLs are not 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. They 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 the Environmental Protection Agency (EPA) 

provides (Barnes and Dourson 1988) to determine reference doses for lifetime exposure (RfDs). 

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 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 LSE Tables. 

Chapter 3 

Health Effects 

Tables and Figures for Levels of Significant Exposure (LSE) 

Tables (3-1, 3-2, and 3-3) and figures (3-1 and 3-2) 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, minimal risk levels 

(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 No-Observed-Adverse-Effect Levels 

(NOAELs), Lowest-Observed-Adverse-Effect Levels (LOAELs), or Cancer Effect Levels (CELs). 
BERYLLIUM	 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 LSE Table 3-1 

(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. 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 2 

"18r" data points in 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 1,1,2,2-tetrachloroethane via 

inhalation for 6 hours per day, 5 days per week, for 3 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, 1 systemic effect (respiratory) was investigated. 
BERYLLIUM	 B-4 

APPENDIX B 

(8)	 NOAEL A No-Observed-Adverse-Effect Level (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 Lowest-Observed-Adverse-Effect Level (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 Cancer Effect Level (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 the NOAEL of 3 ppm in key number 18 was used to derive an 

MRL of 0.005 ppm. 

LEGEND 

See Figure 3-1 

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 intermediate and chronic 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, 18r NOAEL is the critical end point for which an intermediate inhalation 

exposure MRL is based. As you can see from the LSE figure key, the open-circle symbol indicates 

to a NOAEL for the test species-rat. 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 1 of 3 studies for which Cancer Effect Levels were derived. The diamond 

symbol refers to a Cancer Effect Level for the test species-mouse. The number 38 corresponds to 

the entry in the LSE table. 
BERYLLIUM	 B-5 

APPENDIX B 

(18)	 Estimated Upper-Bound Human Cancer Risk Levels This is the range associated with the 

upper-bound for lifetime cancer risk of 1 in 10,000 to 1 in 10,000,000. These risk levels are 

derived from the 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. 
SAMPLE

6 Table 3-1. Levels of Significant Exposure to [Chemical x] – Inhalation 1 

Exposure LOAEL (effect)

Key to frequency/ NOAEL Less serious (ppm) Serious (ppm) figurea Species duration System (ppm) Reference

2 34

6 INTERMEDIATE EXPOSURE

5 6 7 8 9 10

6 Systemic 9 9 9 9 9 9

6 18 Rat 13 wk Resp 3b 10 (hyperplasia) Nitschke et al.

5 d/wk 1981 6 hr/d 

BERYLLIUM B-6
 

APPENDIX B
 CHRONIC EXPOSURE

Cancer38 Rat 39 Rat 40 Mouse 

11

9

18 mo 20 

5 d/wk7 hr/d

89–104 wk 10 

5 d/wk6 hr/d

79–103 wk 10 

5 d/wk6 hr/d 

(CEL, multiple

organs)

(CEL, lung tumors,

nasal tumors)

(CEL, lung tumors,

hemangiosarcomas) 

Wong et al. 1982 NTP 1982 NTP 1982 

a The number corresponds to entries in Figure 3-1.

6 b Used to derive an intermediate inhalation Minimal Risk Level (MRL) of 5 x 10-3 ppm; dose adjusted for intermittent exposure and divided by 12 an uncertainty factor of 100 (10 for extrapolation from animal to humans, 10 for human variability). 
BERYLLIUM B-7
 

APPENDIX B
 

BERYLLIUM C-1 

APPENDIX C 

ACRONYMS, ABBREVIATIONS, AND SYMBOLS 

ACOEM American College of Occupational and Environmental Medicine 

ACGIH American Conference of Governmental Industrial Hygienists 

ADI acceptable daily intake 

ADME absorption, distribution, metabolism, and excretion 

AED atomic emission detection 

AOEC Association of Occupational and Environmental Clinics 

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 

AP alkaline phosphatase 

APHA American Public Health Association 

AST aspartate aminotranferase 

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 

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 
 

BERYLLIUM 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 

Koc organic carbon partition coefficient 

Kow octanol-water partition coefficient 

L liter 

LC liquid chromatography 

LCLo lethal concentration, low 

LC50 lethal concentration, 50% kill 

LDLo lethal dose, low 

LD50 lethal dose, 50% kill 

LDH lactic dehydrogenase 

LH luteinizing hormone 

LT50 lethal time, 50% kill 

LOAEL lowest-observed-adverse-effect level 

LSE Levels of Significant Exposure 

m meter 

MA trans,trans-muconic acid 

MAL maximum allowable level 

mCi millicurie 

MCL maximum contaminant level 

MCLG maximum contaminant level goal 
BERYLLIUM C-3 

APPENDIX C 

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 

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 

NHANES National Health and Nutrition Examination Survey 

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 

OPPTS Office of Prevention, Pesticides and Toxic Substances, EPA 

OPPT Office of Pollution Prevention and Toxics, EPA 

OR odds ratio 

OSHA Occupational Safety and Health Administration 

OSW Office of Solid Waste, EPA 

OW Office of Water 

OWRS Office of Water Regulations and Standards, EPA 

PAH polycyclic aromatic hydrocarbon 

PBPD physiologically based pharmacodynamic 
BERYLLIUM C-4 

APPENDIX C 

PBPK physiologically based pharmacokinetic 

PCE polychromatic erythrocytes 

PEL permissible exposure limit 

PID photo ionization detector 

pg picogram 

pmol picomole 

PHS Public Health Service 

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 

RTECS Registry of Toxic Effects of Chemical Substances 

RQ reportable quantity 

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 

> greater than $ greater than or equal to 

= equal to 

< less than 
BERYLLIUM C-5 

APPENDIX C 

# less than or equal to 

% percent α alpha β beta γ gamma δ delta 

μm micrometer 

μg microgram q1

* cancer slope factor 

– negative 

+ positive 

(+) weakly positive result 

(–) weakly negative result 

BERYLLIUM D-1 

APPENDIX D
 

INDEX 

acute inhalation exposure . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 22, 57, 59 
 

ambient air . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 6, 11, 14, 152, 164, 177, 198
 

Antarctic . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 182 
 

average daily intake . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 173 
 

BCF . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 160 
 

bioaccumulation ............................................................................. 160, 161, 179
 

bioavailability . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 179 
 

bioconcentration . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 149, 160, 179
 

bioconcentration factor (see BCF) . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 160 
 

biomagnification . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 179 
 

biomarker . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 112, 190
 

body weight effects . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 61, 85, 88 
 

breast milk . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 8, 97, 105, 134, 175, 176
 

bronchoalveolar fluid . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 115 
 

cancer . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 6, 7, 9, 13, 15, 16, 20, 65-73, 87, 90, 105, 110, 125, 127, 128, 130, 139, 200
 

carcinogen . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 7, 13, 15, 72, 128, 194, 200
 

carcinogenic . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 13, 15, 16, 19, 20, 72, 73, 125, 128, 194, 200
 

carcinogenicity . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 15, 94, 195, 197
 

carcinoma . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 87 
 

cardiovascular effects . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 57, 82 
 

chronic inhalation exposure . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 23, 123, 127
 

Clean Water Act . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 147, 198
 

deoxyribonucleic acid (see DNA) . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 94, 95 
 

Department of Health and Human Services . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 7 
 

dermal effects . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 15, 61, 84, 89, 126, 128
 

DNA . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 94, 95, 112, 118, 122, 135
 

dog . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 16-18, 86, 87, 127, 184, 193
 

endocrine effects . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 60, 84 
 

FDA . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 9, 169, 197, 200
 

FEDRIP . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 181, 182, 191
 

fetus . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 110, 129
 

fiber . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 14, 47, 147 
 

fish consumption . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 199 
 

Food and Drug Administration (see FDA) . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 9, 200 
 

fruits . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 3, 160, 169, 172, 173
 

garden . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 3, 169, 170
 

gastrointestinal effects . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 13, 14, 17, 18, 82, 133, 193
 

general population . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 11, 67, 112, 126, 128, 130, 151, 173, 176, 180
 

half-life . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 100, 101, 105, 112, 113, 137, 179
 

hematological effects . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 57, 58, 83, 89 
 

Henry’s law . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 140, 141
 

hepatic effects . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 58, 59, 83 
 

immune system . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 130 
 

immunological effects . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 63, 64, 85, 90, 123, 125, 130, 133
 

Integrated Risk Information System . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 200 
 

kidney . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 3, 12, 59, 84, 97-99, 113, 119, 121, 125, 126, 132, 169, 170
 

LD50 . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 74, 94, 125 
 

liver . . . . . . . . . . . . . . . . . . . . . 5, 18, 58, 59, 83, 84, 97-99, 101, 104, 105, 112, 113, 117, 119-122, 125, 126, 132, 133, 174, 185
 

LOAEL . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 16, 17, 19, 20, 23, 48-52, 64, 82, 90, 193 
 

lowest-observed-adverse-effect level (see LOAEL) . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 16 
 

lung . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 6-8, 13-16, 21-23, 46-57, 63, 65-73, 82, 87, 93, 98-102, 105, 107, 108,
 

112, 113, 115, 118-121, 125-128, 131-133, 135, 180, 185, 191
 

lung cancer . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 7, 13, 15, 65-73, 105, 125, 128
 

lymph . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 18, 63, 64, 73, 85, 96, 98, 99, 101, 105, 108, 132
 

lymphoreticular effects . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 62, 85, 89 
 

Mast cells . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 135 
 
BERYLLIUM D-2 

APPENDIX D 

milk . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 8, 97, 105, 111, 120, 134, 171, 173, 175, 176
 

Minimal Risk Levels (see MRL) . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 16, 20 
 

MRL . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 17, 18, 20, 82, 126, 127, 193
 

mullet . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 170 
 

musculoskeletal effects . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 23, 83, 85 
 

National Priorities List (see NPL) . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 1 
 

neurobehavioral . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 86, 109 
 

NIOSH . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 9, 65-67, 138, 139, 175-177, 180, 183, 186, 187, 189, 196, 200
 

NOAEL . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 16-19, 23, 54, 64, 82, 127, 193
 

no-observed-adverse-effect level (see NOAEL) . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 16 
 

NPL . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 1, 11, 149-151, 157, 158, 165, 166, 180
 

ocean . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 2, 159 
 

ocular effects . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 23, 61, 74, 85, 125 
 

odds ratio . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 49, 50, 53 
 

partition coefficients .............................................................................. 140, 141
 

PBPD . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 102 
 

PBPK . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 102-105
 

Permissible Exposure Level . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 200 
 

pharmacodynamic . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 102 
 

pharmacokinetic . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 102-105
 

physiologically based pharmacodynamic (see PBPD) . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 102 
 

physiologically based pharmacokinetic (see PBPK) . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 102, 104
 

precipitation . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 11, 148, 149, 161-164
 

Public health . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 1, 6, 9, 11, 19, 20, 68, 69, 109, 123, 178, 183, 189, 190, 195, 199
 

pulmonary fibrosis . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 47, 57, 135 
 

RCRA ......................................................................................... 147, 153
 

reference dose (see RfD) . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 193, 200
 

regulations . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 9, 147, 148, 193-196, 198, 200
 

renal effects . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 59, 60, 84, 119 
 

reportable quantity . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 198 
 

Resource Conservation and Recovery Act (see RCRA) ................................................... 147, 153
 

RfD . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 193, 197, 200
 

sediment . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 2, 11, 149, 151, 158, 160, 164, 166, 188, 190
 

sedimentation . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 57, 159 
 

selenium . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 112 
 

SMR . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 66-69, 71, 72 
 

soil . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 1-3, 8, 9, 11, 149, 151, 158-160, 164, 166, 176, 179, 180, 186, 188, 190
 

solubility . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 21, 55, 63, 74, 98, 99, 101, 105, 115, 127, 140, 141, 160, 161
 

Standardized mortality ratio (see SMR) . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 66 
 

Superfund . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 151 
 

surface water . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 3, 11, 148, 151, 157, 158, 165
 

thyroid . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 84 
 

time-weighted average (see TWA) . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 69, 200 
 

tomato . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 160, 172
 

total diet studies . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 174 
 

toxicokinetic . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 19, 111, 134
 

Toxics Release Inventory (see TRI) . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 151 
 

TRI . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 151-154, 156, 158, 178, 184
 

tumors . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 6, 73, 87 
 

TWA . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 69, 174, 195, 196, 200
 

Type II . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 55 
 

vapor phase . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 142 
 

vapor pressure . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 140, 141