ORNL
Oak Ridge
National
Laboratory
Operated by
Union Carbide Corporation for the
Department of Energy
Oak Ridge, Tennessee 37830
ORNL/EIS-87
EPA
United States
Environmental Protection
Agency
Office of Research and Development
Health Effects Research Laboratory
Cincinnati. Ohio 45268
EPA-600/1-78-028
REVIEWS OF THE ENVIRONMENTAL
EFFECTS OF POLLUTANTS:
VI. Beryllium
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RESEARCH REPORTING SERIES
Research reports of the Office of Research and Development. U.S. Environmental
Protection Agency, have been grouped into nine series. These nine broad cate-
gories were established to facilitate further development and application of en-
vironmental technology. Elimination of traditional grouping was consciously
planned to foster technology transfer and a maximum interface in related fields.
The nine series are:
1. Environmental Health Effects Research
2. Environmental Protection Technology
3. Ecological Research
4. Environmental Monitoring
5. Socioeconomic Environmental Studies
6. Scientific and Technical Assessment Reports (STAR)
7. Interagency Energy-Environment Research and Development
8. "Special" Reports
9. Miscellaneous Reports
This report has been assigned to the ENVIRONMENTAL HEALTH EFFECTS RE-
SEARCH series. This series describes projects and studies relating to the toler-
ances of man for unhealthful substances or conditions. This work is generally
assessed from a medical viewpoint, including physiological or psychological
studies. In addition to toxicology and other medical specialities, study areas in-
clude biomedical instrumentation and health research techniques utilizing ani-
mals — but always with intended application to human health measures.
This document is available to the public through the National Technical Informa-
tion Service, Springfield, Virginia 22161.
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ORNL/EIS-87
EPA-600/1-78-028
November 1978
REVIEWS OF THE ENVIRONMENTAL EFFECTS OF POLLUTANTS: VI. BERYLLIUM
by
John S. Drury, Carole R. Shriner, Eric B. Lewis,
Leigh E. Towill, and Anna S. Hammons
Information Center Complex, Information Division
Oak Ridge National Laboratory
Oak Ridge, Tennessee 37830
operated by
Union Carbide Corporation
for the
U.S. Department of Energy
Reviewer and Assessment Chapter Author
Andrew Reeves
Wayne State University
Detroit, Michigan 48202
Interagency Agreement No. D5-0403
Project Officer
Jerry F. Stara
Office of Program Operations
Health Effects Research Laboratory
Cincinnati, Ohio 45268
Noveinber 1978
Prepared for
HEALTH EFFECTS RESEARCH LABORATORY
OFFICE OF RESEARCH AND DEVELOPMENT
U.S. ENVIRONMENTAL PROTECTION AGENCY
CINCINNATI, OHIO 45268
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This report was prepared as an account of work sponsored by an agency
of the United States Government. Neither the United States Government nor
any agency thereof, nor any of their employees, contractors, subcontractors,
or their employees, makes any warranty, express or implied, nor assumes any
legal liability or responsibility for any third party's use or the results
of such use of any information, apparatus, product or process disclosed in
this report, nor represents that its use by such third party would not
infringe privately owned rights.
This report has been reviewed by the Health Effects Research Laboratory,
U.S. Environmental Protection Agency, and approved for publication. Approval
does not signify that the contents necessarily reflect the views and policies
of the U.S. Environmental Protection Agency, nor does mention of trade names
or commercial products constitute endorsement or recommendation for use.
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CONTENTS
Figures v
Tables vii
Foreword xi
Acknowledgments xiii
Highlights xv
1. Summary = 1
1.1 Properties and Analysis 1
1.2 Biological Aspects in Microorganisms 2
1.3 Biological Aspects in Plants i 3
1.4 Biological Aspects in Wild and Domestic Animals 3
1.5 Biological Aspects in Humans and Experimental Animals. ... 3
1.6 Environmental Occurrence 4
1.7 Conclusions 5
2. Chemical and Physical Properties and Analysis 8
2.1 Summary 8
2.2 Physical and Chemical Properties 10
2.2.1 Beryllium . 10
2.2.2 Beryllium Oxide (Beryllia) 21
2.2.3 Beryllium Sulfate 23
2.2.4 Beryllium Hydroxide 27
2.2.5 Beryllium Halides and the Fluoroberyllates 28
2.2.6 Beryllium Alloys 32
2.2,7 Beryllides 35
2.2.8 Beryllium Nitrate 37
2.2.9 Beryllium Minerals 38
2.2.10 Other Beryllium Compounds 38
2.3 Analysis for Beryllium 38
2.3.1 Sampling and Sample Handling 41
2.3.2 Separation and Concentration Methods 48
2.3.3 Methods of Analysis 52
2.3.4 Comparison of Analytical Procedures 63
3. Biological Aspects in Microorganisms 77
3.1 Summary 77
3.2 Metabolism 77
3.3 Effects 77
3.3.1 Physiological Effects 77
3.3.2 Toxic Effects 78
4. Biological Aspects in Plants 80
4.1 Summary 80
4.2 Metabolism 80
4.2.1 Uptake 80
4.2.2 Translocation 82
4.2.3 Distribution 83
4.2.4 Bioelimination 83
4.3 Effects -. 83
5. Biological Aspects in Wild and Domestic Animals 89
5.1 Summary 89
5.2 Aquatic Organisms 89
5.2.1 Metabolism: Uptake and Distribution 89
iii
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IV
5.2.2 Effects 89
5.3 Birds. 96
5.3.1 Metabolism: Uptake and Distribution 96
5.3.2 Effects 96
5.4 Mammals 97
5.4.1 Metabolism 97
5.4.2 Physiological and Toxic Effects 97
6. Biological Aspects in Humans 102
6.1 Summary 102
6.2 Metabolism 103
6.2.1 Uptake and Absorption 103
6.2.2 Transport, Distribution, and Accumulation 104
6.2.3 Elimination 112
6.3 Effects 119
6.3.1 Potential Exposure Sources 119
6.3.2 Physiological Effects 122
6.3.3 Acute Beryllium Disease 128
6.3.4 Chronic Beryllium Disease 139
6.3.5 Carcinogenesis 147
6.3.6 Teratogenicity and Mutagenicity 151
7. Environmental Distribution and Transformation 167
7.1 Summary 167
7.2 Production and Usage 168
7.3 Distribution of Beryllium in the Environment 172
7.3.1 Sources of Pollution 172
7.3.2 Distribution in Rocks and Soils 175
7.3.3 Distribution in Water and Sediments 180
7.3.4 Distribution in Air 181
7.4 Environmental Fate 184
7.4.1 Mobility and Persistence in Soils 184
7.4.2 Mobility and Persistence in Water 184
7.4.3 Mobility and Persistence in Air 184
7.5 Waste Management 184
7.6 Beryllium in Foods 185
7.7 Biomagnification in Food Chains 185
8. Environmental Assessment of Beryllium 192
8.1 Environmental Occurrence 192
8.1.1 Natural Background 192
8.1.2 Contribution by Human Activities 192
8.2 Toxicity 193
8.2.1 From Skin Contact 193
8.2.2 From Ingestion 193
8.2.3 From Inhalation 193
8.3 Safe Levels 194
8.3.1 Air 194
8.3.2 Water 195
8.3.3 Foods 196
8.3.4 Cigarettes 196
8.4 Monitoring of Safe Levels 197
8.4.1 Direct Analysis 197
8.4.2 Biological Monitoring 197
8.5 Summary Opinion and Research Needs 197
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FIGURES
2.1 Calculated distribution of the beryllium species Be3(OH)33+,
BeaOH3+, and Be5(OH)73+ 13
2.2 Two possible chronic beryllium disease mechanisms 20
2.3 Manufacture of beryllium oxide ceramic products 24
2.4 An arc furnace used in preparing beryllium copper 33
2.5 Flowsheet for the production of beryllium copper from beryllium
oxide 34
2.6 Adsorption of beryllium on the walls of polyethylene and glass
vessels as a function of the pH of the solution 44
2.7 Sampling train " 46
2.8 Extraction curves of beryllium, copper, magnesium, zinc, cal-
cium, strontium, and barium with a 0.1 M solution of acetyl-
acetone in benzene as a function of the pH of the aqueous
solution 49
2.9 Schematic diagram for the Unicam SP 1900, a double-beam
spectrophotometer 52
2.10 Cross section of the HGA-2000 (Perkin-Elmer) graphite oven. ... 54
2.11 A schematic diagram of a filter-type fluorometer 57
2.12 Schematic diagram of a gas chromatograph 62
3.1 The growth of algae (70 hr) as a function of the initial pH of
the nutrient solution (one of four similar experiments) .... 78
6.1 Pulmonary beryllium levels during and after BeSO/, exposure in
rats Ill
6.2 Tracheobronchial lymph node beryllium levels during and after
BeSO/, exposure in rats. . ." Ill
6.3 The blood clearance of 7Be injected with and without a carrier
in rabbits 113
6.4 Occurrence of urinary beryllium excretion by years from last
exposure in 38 patients 115
6.5 Urinary excretion of beryllium in male rats fed Be2 in
drinking water 117
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vi
6.6 7Be bile excretion in rats after intravenous administration
of 7BeCl2 120
6.7 The inhibition of Na-K ATPase and BeCla concentration 124
6.8 Animal mortality rate following exposure to 47 mg of BeSO*
per cubic meter by inhalation 138
6.9 Proposed mechanism for the latency of chronic beryllium disease, 140
6.10 Delay in symptom onset of 76 cases of chronic beryllium disease
reported to the Beryllium Case Registry since 1966 143
7.1 Supply-demand relationships for beryllium, 1968 170
7.2 Areas of the conterminous United States in which beryllium
deposits are most likely to be found 178
7.3 Beryllium content of surficial materials of the United States. . 179
7.4 Falloff of ground beryllium concentration with distance away
from a beryllium production plant 183
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TABLES
2.1 Physical properties of beryllium 12
2.2 Calculated thermodynamic quantities for the hydrolysis
reactions at 25°C 14
2.3 Beryllium minerals 15
2.4 Physical properties of beryllium oxide (beryllia) 22
2.5 Sources of beryllium ceramic plant emissions 25
2.6 Solubility of beryllium sulfate tetrahydrate in water 25
2.7 Degree of hydrolysis of beryllium sulfate solutions at 25°C. . . 25
2.8 Acidity of beryllium sulfate solutions at 20°C 26
2.9 Properties of the beryllium halides 29
2.10 Acidity of aqueous beryllium fluoride solutions as a function
of concentration 30
2.11 Solubility of alkali fluoroberyllates at 25°C 30
2.12 Solubility of beryllium chloride in water 31
2.13 Acidity of aqueous beryllium chloride solutions as a function
of concentration 31
2.14 Physical properties of beryllium copper No. 25 strip before
and after heat treatment 32
2.15 Beryllide types 35
2.16 High-temperature oxidation-resistant beryllides 36
2.17 Thermal conductivity of several beryllides 36
2.18 Room-temperature hardness of selected beryllides 37
2.19 Properties of selected beryllium compounds 39
2.20 Methods for determining beryllium: atomic absorption
spectroscopy 40
2.21 Methods for determining beryllium: spectrophotometry 41
2.22 Methods for determining beryllium: fluorometry 42
vii
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viii
2.23 Methods for determining beryllium: spectrometry A3
2.24 Methods for determining beryllium: gas chromatography 44
2.25 Beryllium concentration in orchard leaves as a function of
organic digestion procedure 45
2.26 Beryllium in NBS orchard leaves 45
2.27 Ion exchange methods for separating beryllium 51
2.28 Summary of interlaboratory comparisons of beryllium by flame
atomic absorption spectroscopy 53
2.29 Recovery of beryllium from spiked urine and spiked ashed urine
based on aqueous standards 54
2.30 Beryllium content of NBS standard reference materials 55
2.31 Complexing agents commonly used for the spectrophotometric
determination of beryllium 56
2.32 Spectrographic methods of determining beryllium 59
2.33 Relationship between spectroscopic sensitivity for beryllium
and size of sample 60
2.34 Recovery of beryllium added to 2-mg quantities of rabbit
liver ash 60
2.35 Recovery of beryllium from spiked samples 61
4.1 Beryllium concentration in plant material exposed to beryllium
in nutrient solutions 81
4.2 Beryllium concentration in bush beans exposed to beryllium in
nutrient solutions 81
4.3 Yield of kale with beryllium applied at different stages of
growth 82
4.4 Beryllium content in plants 84
4.5 Phytotoxic effect exerted by beryllium on plants of economic
importance in Illinois 85
5.1 Effects of Be(N03)2»3H20 on regeneration of limbs in adult
Tri-twms 91
5.2 Results of treatment of frog embryos with beryllium 92
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IX
5.3 The 96-hr median tolerance limits (TL50) of several less
common metals to fish 93
5.4 Median lethal concentrations (LC50) and median lethal times
(LTSO) for flagfish fry exposed to beryllium sulfate 93
5.5 Median lethal concentrations (LCSo) for juvenile goldfish
exposed to beryllium sulfate 94
5.6 Median lethal concentrations (LC50) for juvenile fathead
minnows exposed to beryllium sulfate 94
5.7 Median tolerance limits of guppies to beryllium sulfate in
water of varying hardness 95
5.8 Median tolerance limits of salamanders to beryllium sulfate by
graphic interpolation 95
5.9 Acute toxicity of Be'SO/, solutions to unexposed and previously
exposed guppies 96
5.10 Recovery of 7Be in tissues of a cow 119 hours after intravenous
administration 98
5.11 Recovery of 7Be in tissues of three calves after a single oral
dose 99
6.1 Tissue distribution of beryllium . '. 105
6.2 Distribution of intravenously injected beryllium compounds 24
hours following injection in rats 106
6.3 Redistribution and excretion of beryllium in rats 107
6.4 Distribution of 7Be in rats after intraperitoneal injection. . . 109
6.5 Tissue distribution and balance of beryllium in rats fed
BeS04 in drinking water 110
6.6 Beryllium (7BeSO<») in subcellular fractions from rat liver
after various doses injected intravenously . 112
6.7 Effective retention of 7Be in mice, rats, monkeys, and dogs. . . 114
6.8 Beryllium workers and neighborhood residents 116
6.9 Excretion of 7Be 118
6.10 Daily fecal excretion of 7Be in rabbits and rats 119
6.11 Effect of beryllium on various enzymes 123
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X
6.12 Skin response to oral administration and intradermal injec-
tion of BeSOi,, Be-ATA, Be-H citrate, and Be-albuminate in
guinea pigs 127
6.13 Clinical progress of acute beryllium pneumonitis . 131
6.14 Laboratory findings of acute beryllium pneumonitis 132
6.15 Effects on various animal species caused by exposure to
beryllium by inhalation 133
6.16 Symptoms of 76 cases of chronic beryllium disease reported to
the Beryllium Case Registry since 1966 142
6.17 Mortality of chronic beryllium disease by industry up to 1966. . 145
6.18 Clinical data on patients with chronic beryllium disease .... 146
6.19 Beryllium compounds explored for carcinogenicity 148
6.20 Osteosarcomas induced by beryllium 15C
7.1 Uses of beryllium 169
7.2 Forecast of beryllium demand 171
7.3 United States reserves of beryllium 171
7.4 Sources of beryllium emissions to the environment 172
7.5 Average beryllium content of coal ash 173
7.6 Characterization of the emissions of beryllium extraction
plants 174
7.7 Beryllium emissions by state, 1968 176
7.8 Beryllium in rocks and minerals 177
7.9 Representative beryllium minerals 178
7.10 Beryllium in Australian waters 180
7.11 Average beryllium concentrations in urban and rural areas. . . . 182
7.12 Recommended cleaners for beryllium handling operations 183
7.13 Beryllium in Australian foods 185
7.14 Beryllium in West German food crops 187
7.15 Beryllium in West German cigarettes 187
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FOREWORD
A vast amount of published material is accumulating as numerous
research investigations are conducted to develop a data base on the
adverse effects of environmental pollution. As this information is
amassed, it becomes continually more critical to focus on pertinent,
well-designed studies. Research data must be summarized and interpreted
in order to adequately evaluate the potential hazards of these substances
to ecosystems and ultimately to public health. The Reviews of the Environ-
mental Effects of Pollutants (REEPs) series represents an extensive com-
pilation of relevant research and forms an up-to-date compendium of the
environmental effect data on selected pollutants.
Reviews of the Environmental Effects of Pollutants: VI. Beryllium
includes information on chemical and physical properties; pertinent
analytical techniques; transport processes to the environment and sub-
sequent distribution and deposition; impact on microorganisms, plants,
and wildlife; toxicologic "data in experimental animals including metabo-
lism, toxicity, mutagenicity, teratogenicity, and carcinogenicity; and an
assessment of its health effects in man. The large volume of factual
information presented in this document is summarized and interpreted in
the final chapter, "Environmental Assessment," which presents an overall
evaluation of the potential hazard resulting from present concentrations
of beryllium in the environment. This final chapter represents a major
contribution by Andrew L. Reeves from Wayne State University.
The REEPs are intended to serve various technical and administrative
personnel within the Agency in the decision-making processes, i.e., in
the development of criteria documents and environmental standards, and
for other regulatory actions. The breadth of these documents makes them
a useful resource for public health personnel, environmental specialists,
and control officers. Upon request these documents will be made available
to any interested individuals or firms, both in and out of the government.
Depending on the supply, the document can be obtained directly by writing
to:
Dr. Jerry F. Stara
U.S. Environmental Protection Agency
Health Effects Research Laboratory
26 W. St. Glair Street
Cincinnati, Ohio 45268
R. J. Garner
Director
Health Effects Research Laboratory
xi
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ACKNOWLEDGMENTS
The authors are particularly grateful to Carlos Bamberger, Oak
Ridge National Laboratory (ORN1.) , and Kenneth A. Walsh, Brush-Wellman
Inc., Cleveland, Ohio, for reviewing preliminary drafts of this report
and for offering helpful comments and suggestions. The advice and sup-
port of Gerald U. Ulrikson, Manager, Information Center Complex, and
Jerry F. Stara, EPA Project Officer, and the cooperation of the Toxicol-
ogy Information Response Center, the Environmental Mutagen Information
Center, and the Environmental Resource Center of the Information Center
Complex, Information Division, ORNL, are gratefully acknowledged. The
authors also thank L. F. Truett and P. M. Hafford, editors, and Donna
Stokes and Patricia Hartman, typists, for preparing the manuscript for
publication.
Appreciation is also expressed to Bonita M. Smith, Karen L. Blackburn,
and Donna J. Sivulka for EPA in-house reviews and editing and for coordi-
nating contractual arrangements. The efforts of Allan Susten and Rosa
Raskin in coordinating early processing of the reviews were important in
laying the groundwork for document preparation. The advice of Walter E.
Grube was valuable in preparation of manuscript drafts. The support of
R. John Garner, Director of Health Effects Research Laboratory, is much
appreciated. Thanks are also expressed to Carol A. Haynes and Peggy J.
Bowman for typing correspondence and corrected reviews.
xiii
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HIGHLIGHTS
This study is a comprehensive, multidisciplinary review of the health
and environmental effects of beryllium and specific beryllium derivatives.
Over 330 references are cited.
Commercially, beryllium is used as the metal, as beryllium-copper
alloys and other alloys, and as beryllium oxide ceramic products. United
States production of beryllium metal is about 45 to 68 metric tons per
year. Human exposure to beryllium is an industrial problem from process-
ing and fabrication of beryllium products. The primary nonoccupational
source of beryllium exposure is coal combustion. Beryllium has also been
added to the atmosphere from mining, extracting, and machining; foundry
operations; ceramic plant operations; space vehicle and rocket fuel manu-
facture; and nuclear reactor and classified weapons manufacture.
The high toxicity of beryllium compounds is manifest only after inha-
lation. Acute chemical pneumonitis and chronic pulmonary granulomatosis
(berylliosis) have been observed in humans following beryllium inhalation.
Chronic berylliosis eventually involves the adrenals, liver, kidney, and
heart. Some beryllium compounds can cause malignancies in experimental
animals, but epidemiological studies have failed to demonstrate a rela-
tionship between beryllium and human cancer. No data were found concern-
ing teratogenic or mutagenic effects of beryllium compounds. The existing
occupational standard of 2 yg/m3 is thought adequate to prevent acute and
chronic beryllium disease in the industrial population. Current beryllium
emissions from industries are controlled so that there is apparently no
hazard to the general population.
This report was submitted in partial fulfillment of Interagency
Agreement No. D5-0403 between the Department of Energy and the U.S. Envi-
ronmental Protection Agency. The draft report was submitted for review
on March 1977. The final report was completed in October 1977.
xv
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SECTION 1
SUMMARY
1.1 PROPERTIES AND ANALYSIS
Beryllium is a moderately rare element, existing naturally only as
9Be in some forty-odd mineralized forms. Principal among these are beryl,
a beryllium aluminum silicate, and bertrandite, a hydrated beryllium disil-
icate. These minerals are mined and beryllium hydroxide recovered. Beryl
ore is usually obtained as a by-product of other mining operations. Most
is imported from Brazil, South Africa, Argentina, and Uganda (1969 data),
with less than 10% of the U.S. consumption coming from domestic sources
(Section 2.2.9). Commercially, beryllium is used as the metal (about one-
third of U.S. consumption), as beryllium-copper alloys (about 50%) and
other alloys (about 10%), and as beryllium oxide ceramic products (about
5%) (Section 2.2.9).
Beryllium metal is steel gray and brittle. It is the only stable
light metal with an unusually high melting point, a high modulus of elas-
ticity, a low coefficient of thermal expansion, and a high stiffness-to-
weight ratio. These are specifications required for certain aerospace
and precision instrument applications. Metallic beryllium is also a good
thermal and electrical conductor. Due to its low atomic weight, it is
relatively transparent to x rays and is used as window material in some
x-ray tubes. Its low neutron absorption cross section and high melting
point recommend beryllium as structural and moderator materials for cer-
tain nuclear reactors (Section 2.2.1).
Beryllium oxide, beryllia, is a colorless crystalline solid or an
amorphous white powder with an extremely high melting point, high thermal
conductivity, low thermal expansion, and high electrical resistivity.
Beryllia powder is compacted to form a ceramic material which has appli-
cations as nuclear reactor reflectors and moderators, high-voltage elec-
trical components, spark plug insulators, combustion chamber liners for
rockets, inertial guidance components, laser tubes, and electric furnace
liners (Section 2.2.2).
Beryllium sulfate, usually BeSOi,»4H20, is soluble in water and insol-
uble in ethanol. In aqueous solution, beryllium sulfate and other soluble
beryllium salts are readily hydrolyzed, increasing the hydrogen ion con-
centration of the solution. If a buffer is present to remove the hydrogen
ions, the beryllium salt can be completely converted to the insoluble
hydroxide, which has an extremely long residence time in the body. Such
precipitation can be reduced or prevented if the soluble beryllium salt
is first chelated, for example by oxalic or citric acid (Section 2.2.3).
Although there is very little demand for beryllium sulfate, it is used
occasionally in the laboratory.
Beryllium hydroxide is an important intermediate in all of the cur-
rently used methods for refining beryllium from its ores. As discussed
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above, its insoluble nature makes Be(OH)2 important physiologically, since
it is retained in various tissues under normal conditions (Section 2.2.4).
Beryllium fluoride (BeF2) and beryllium chloride (BeCla) are conven-
tionally used in the commercial preparation of metallic beryllium, the
former in the United States and the latter in France. The fluoroberyllate
ion (BeFi,2") can form from the interaction of BeF2 with fluorides of the
alkali and alkaline earth metals, yielding fluoroberyllates of the general
types M2^BFi, and M^BF^,. Structurally these compounds are similar to sili-
cates, and they have been used in the production of unique fluoroberyllate
glasses having low dispersion and a wide transmission range (Section 2.2.5).
The bromide and iodide of beryllium are seldom used, except for research.
Beryllium alloys are valuable because they display greatly improved
strength, hardness, durability, and resistance to fatigue. Applications
for these alloys are found in communications, computer, electronic, and
electrical industries. The primary beryllium alloy is with copper; but
others include beryllium-nickel, beryllium-aluminum, and beryllium-iron
(Section 2.2.6).
Beryllides, intermetallic compounds of beryllium, are typically pre-
pared by heating the blended metal powders and then consolidating the mate-
rials by hot-pressing techniques. The small amounts of beryllides produced
are used for high-temperature components in nuclear power plants, special
turbine engines, and nuclear equipment. Toxicity and carcinogenicity test-
ing indicates little or no biologic activity for beryllides, in spite of
their relatively high beryllium content (Section 2.2.7).
Beryllium nitrate [Be(N03)2«3H20] is used to stiffen mantles for gas
lamps. There is a potential health hazard during the first 15 min of burn-
ing a new mantle, when most of the beryllium salt is volatilized (Section
2.2.8).
A variety of analytical techniques are available for detection and
quantitation of beryllium, and in some cases, these techniques are sensi-
tive to less than 1 ppb. A major consideration is the nature of the sample
to be analyzed and the special requirements for preparation of biological,
air, water, and ore samples (Section 2.3.1). Procedures in use are atomic
absorption spectrophotometry, fluorometry, emission spectroscopy, and gas
chromatography (Section 2.3.3). Newer developments have made atomic absorp-
tion spectrophotometry the most convenient and useful technique except where
very great sensitivity is required (i.e., less than about 2 ppb). The gas
chromatographie method is sensitive to as little as 0.08 pg of beryllium,
with usually rapid and convenient sample preparation for environmental and
biological samples (Section 2.3.4).
1.2 BIOLOGICAL ASPECTS IN MICROORGANISMS
Microorganisms absorb beryllium when exposed to soluble compounds
(Section 3.3.1). Increased growth results in some magnesium-deficient
species when dilute alkaline solutions of beryllium salts are added, but
such compounds generally prove toxic to microorganisms at or below pH 7
-------
(Section 3.3.2). Toxic thresholds vary widely, depending on pH, growth
conditions, Mg2+ concentration, and the particular microorganism in
question.
1.3 BIOLOGICAL ASPECTS IN PLANTS
Normally, plant beryllium levels are very low, but soluble beryllium
compounds can be taken up by roots, especially in acid soils (Section
4.2.1). Although there is poor translocation of beryllium to the shoots
of bean, barley, sunflower, and tomato plants, corn appears to be an excep-
tion (Section 4.2.2). There is no indication that plants can eliminate
beryllium, other than by abscission of dead leaves. Further, beryllium
can be concentrated several hundredfold by roots from nutrient solution
(Section 4.2.1). About 2 ppm beryllium inhibits growth of a variety of
plants. Although beryllium inhibits plant phosphatase in vitro, no effect
on enzyme activity has been detected in vivo (see Sections 4.3 and 6.3.2.1).
No specific toxic effects are noted for beryllium poisoning in plants, but
beryllium does enhance the yield of ethyl methanesulfonate-induced chromo-
some aberrations (Section 4.3).
1.4 BIOLOGICAL ASPECTS IN WILD AND DOMESTIC ANIMALS
Beryllium effects have been noted in amphibia, molluscs, fish, birds,
and cattle. Limb regeneration in salamander larvae can be inhibited by
topical application of beryllium; regeneration proceeds upon removal of
the beryllium-inhibited stump. Normal embryonic development is retarded
by Be2+ treatment of frog and snail eggs (Section 5.2.2.1).
Fish exhibit a toxic beryllium response which increases with decreas-
ing water hardness. There are some data suggesting that fish can develop
a limited tolerance to beryllium (Section 5.2.2.2).
Cattle fed radioactive 7BeCl2 accumulated most of the absorbed beryl-
lium in the liver, kidney, and skeletal system. However, over 68% of the
initial dose was rapidly eliminated in the feces and urine. Milk contained
less than 0.002% of the beryllium (Sections 5.4.1.1 and 5.4.2).
1.5 BIOLOGICAL ASPECTS IN HUMANS AND EXPERIMENTAL ANIMALS
Beryllium exposure to humans is an industrial problem and can be a
problem to the general population living in the vicinity of industrial
sources (Section 6.3.1). Inhalation is the primary route of uptake, fol-
lowed by ingestion and skin absorption. Uptake by ingestion and skin
absorption contribute only insignificant amounts to the total body burden.
Inhaled beryllium is retained in the lungs and slowly mobilized to the
blood, whereas ingested beryllium is poorly absorbed in the intestine and
quickly passes out of the body in the feces. Urinary excretion of ingested
beryllium is minimal. Beryllium that reaches the bloodstream is rapidly
distributed to various tissues and stored, chiefly in pulmonary lymph nodes
and bone, for long periods of time. The ultimate storage site is the
skeleton (Section 6.2.2).
-------
The most likely fundamental reason for the chronic toxicity of beryl-
lium is its immunologic behavior. The Be ion is an allergen (hapten) to
which delayed (cell-mediated) hypersensitivity develops in skin and perhaps
in other organs. The symptoms of beryllium disease are thought to be the
manifestations of autoimmunity. Two additional theories of beryllium toxic-
ity, applicable in certain situations, are: (1) beryllium affects phosphate
metabolism by inhibiting the enzymes alkaline phosphatase, phosphoglucomu-
tase, and to a lesser extent, other phosphate-transferring enzymes (Section
6.3.2.1); or (2) beryllium exerts its effects by complexing with the cellu-
lar DNA, inhibiting replication and cell proliferation (Section 6.3.2.2).
Beryllium compounds react selectively only with certain proteins; cytoplas-
mic protein changes from a soluble to insoluble form, but proteins in nuclei
and mitochondria are unaltered (Section 6.3.7.3).
Beryllium skin contact can result in allergic dermatitis, skin ulcers,
and conjunctivitis. Acute contact dermatitis is generally associated with
soluble fluoride or sulfate salts of beryllium, whereas insoluble beryllium
oxide powder may cause cutaneous granulomas (Section 6.3.3). Acute beryl-
lium pneumonitis results from inhalation of soluble compounds in relatively
high concentrations. All segments of the respiratory tract may be involved,
with rhinitis, pharyngitis, and tracheobronchitis. Although there were some
fatalities from the acute syndrome, recovery after several weeks or months
was the rule and no nonoccupational cases were observed.
Chronic beryllium disease can be latent up to 20 years. The manifesta-
tion may be related to stress situations such as infection or surgery. The
main lesion is pulmonary granulomatosis; it is thought that altered adrenal
function, related to stress, triggers beryllium translocation, which in
turn, leads also to liver and kidney damage. Diagnosis is difficult without
knowledge of beryllium exposure history (Section 6.3.4). Chronic beryllium
disease becomes progressively more severe and resulted in 30% mortality in
the early years. Complication of cor pulmonale with myocardial decompen-
sation was the common cause of death. This disease occurs in industrial
workers and has been found among residents in the near vicinity, usually
within a 3/4-mile radius of the point source. Cases in the general popula-
tion result from airborne beryllium carried from the plant or from handling
workers' contaminated clothing. An effective treatment of chronic beryl-
lium disease involves long-term therapy with steroids and the adrenocorti-
cotropic hormone (Section 6.3.4.7).
Some beryllium compounds (beryllium oxide, beryllium sulfate, beryllium
fluoride, beryllium phosphate, and the phosphor zinc manganese beryllium
silicate) are capable of inducing malignant tumors in experimental animals.
However, epidemiological studies have failed to demonstrate a relationship
between beryllium and human cancer (Section 6.3.5). No data were found
concerning human teratogenic or mutagenic effects by beryllium compounds
(Section 6.3.6).
1.6 ENVIRONMENTAL OCCURRENCE
The primary source of human exposure to beryllium is through processing
and fabrication of beryllium products. Current limits for such operations
-------
are 2 yg of beryllium per cubic meter (8-hr average) for plant workers and
0.01 yg/m3 (30-day average) or 10 g in 24 hr for plant emissions (Section
7.3). Sampling of 100 U.S. locations indicated an average daily concentra-
tion of less than 0.0005 yg/m3 (Section 7.3.4). Pollution control devices
are now used throughout the industry, and the beryllium concentration in
the U.S. atmosphere does not appear to present a health hazard.
United States production of beryllium metal is about 45 to 68 metric
tons (50 to 75 tons) per year. It is estimated that annual domestic con-
sumption will increase to approximately 1500 metric tons by the year 2000
and that about half the ore will be mined within the United States (Section
7.2).
According to 1968 data (Section 7.3.1), an annual total of 148 metric
tons (164 tons) of beryllium is released to the U.S. environment from a
variety of sources. Coal combustion accounts for 85% of the beryllium
released to the environment, while beryllium production is responsible for
only 4%. However, 25% of the domestic beryllium pollution is released in
Pennsylvania and Ohio, where the two American beryllium producers are
located.
Prior to implementation of pollution control devices, airborne beryl-
lium pollution was as much as 500-fold higher in the vicinity of beryllium
plants than it is now. Now, with efficient emission control, there is no
apparent hazard (Section 7.3.4).
Beryllium in rocks and minerals generally ranges from 1 to 10 ppm,
although beryl ore can contain up to 5%. The worldwide average soil con-
centration (about 6 ppm) is much higher than the average U.S. soil concen-
tration (about 1 ppm) (Section 7.3.2).
The beryllium concentration in natural waters is essentially nil
(Section 7.3.3).
Since beryllium is so valuable, there is very little solid beryllium
waste. Beryllium scrap is salvaged and resold to producers. Beryllium
trapped by pollution control devices is also recycled by producers, and
that not recycled is buried in sealed containers (Section 7.5).
The limited information available indicates low beryllium levels in
foods (Section 7.6). No direct information on biomagnification of beryl-
lium in animals was found, but since there is very little beryllium absorp-
tion from ingested sources (Section 6.2), we suggest that human consumption
of beryllium in foods presents no health hazard at present levels (Section
7.7).
1.7 CONCLUSIONS
1. The primary nonoccupational source of beryllium exposure is coal com-
bustion; however, the most significant human health hazard is to
beryllium workers.
-------
2. Ingested beryllium is only poorly absorbed through the intestine but
can be efficiently retained in the lungs after inhalation. A few
cases of toxic exposure by skin contact have also been reported.
3. Beryllium mobilized in the bloodstream, for example from the lungs,
can be deposited in liver and bone as the insoluble hydroxide.
4. Currently, the methods of choice for beryllium analysis are atomic
absorption spectroscopy and gas chromatography.
5. Beryllium production in the United States is about 45 to 68 metric
tons annually.
6. There is very little beryllium waste because it is economically fea-
sible to recycle the metal, both from commercial products and from
emissions trapped by pollution control devices.
7. Beryllium does not appear to move efficiently through the environment
(except in the atmosphere) or through the food chain. It is generally
undetectable in natural waters. Beryllium is strongly fixed in many
soils, since it can displace other divalent cations which share common
sorption sites.
8. Beryllium can partially replace the magnesium requirement in micro-
organisms and plants, but it becomes toxic at higher levels, especially
at neutral to low pH.
9. Three theories regarding the mechanism of beryllium toxicity are:
(1) beryllium hypersensitivity due to allergic reactions, (2) beryl-
lium inhibition of phosphate-transferring enzymes, and (3) beryllium
complexation with DNA.
10. Certain beryllium compounds can induce malignant tumors in experi-
mental animals, but epidemiological studies have failed to show a
correlation between beryllium exposure and human cancer.
11. Acute beryllium disease, generally resulting from inhalation and skin
contact, is manifested in respiratory symptoms, dermatitis, skin ulcers,
and conjunctivitis.
12. Chronic beryllium disease can be latent for up to 20 years. The onset
of symptoms appears to be correlated with stress situations such as
infection or surgery and involves pulmonary granulomatosis with
necrosis in liver and kidney. The Untreated condition resulted in
30% mortality in the early years.
13. No information exists on the teratogenic properties of beryllium
compounds in mammals. Beryllium does have inhibitory and teratogenic
effects on amphibian embryogenesis.
14. Beryllium can enhance the yield of mutagen-induced chromosome aberra-
tions in plants.
-------
15. No data were found indicating that beryllium is biomagnified in the
food chain. In fact, data describing the inefficient absorption of
ingested beryllium suggest that biomagnification is unlikely.
16
At present levels, beryllium does not appear to present any health
hazard to the general population.
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SECTION 2
CHEMICAL AND PHYSICAL PROPERTIES AND ANALYSIS
2.1 SUMMARY
Beryllium is a moderately rare element, ranking 44th in abundance and
constituting about 0.0006% of the earth's crust. Discovered by Vauquelin
in 1798, the element was first named glucinium or glucinum because of the
sweet taste of its salts; its present name was officially sanctioned by
the International Union of Pure and Applied Chemistry in 1957.
Beryllium does not occur in the elementary state in nature — it is
found in some forty-odd mineralized forms, which are widely distributed
in the earth's crust, but only rarely in concentrations suitable for min-
ing. The most important of these minerals are beryl, a beryllium alumi-
num silicate which has the composition 3BeO«Al203»6Si02, and bertrandite,
a hydrated disilicate which has the composition 4BeO»2Si02«H20. The lat-
ter has been mined commercially only since 1969. Beryllium hydroxide has
been recovered from beryl by means of the Copaux-Kawecki fluoride process
or by the more current Sawyer-Kjellgren sulfate process. In the first
method, not used since 1970, ore is roasted with sodium fluoroferrate(III),
which converts the insoluble beryllium mineral to a soluble form, sodium
fluoroberyllate. The latter is heated with alkali to form beryllium hy-
droxide. In the sulfate process, refractory ore is melted, quenched, heat
treated, and leached with sulfuric acid; the resulting beryllium sulfate
is converted to the hydroxide by treatment with alkali. Beryllium hydrox-
ide can be recovered from pulverized bertrandite ore by leaching directly
with sulfuric acid. The beryllium sulfate thus obtained is purified by
solvent extraction and converted to hydroxide after treatment with aqueous
ammonium carbonate.
The most important commercial forms of the element are the metal it-
self, beryllium-copper alloys, and beryllium oxide. All these forms are
prepared from beryllium hydroxide. The oxide is obtained by calcining
the sulfate, the metal is prepared by converting the oxide to beryllium
fluoride and reducing the latter with magnesium metal, and the beryllium-
copper alloys are made by reducing beryllium oxide with carbon in the
presence of molten copper.
The pure metal is steel gray and brittle; it has several unique
properties that make it attractive, and sometimes essential, to designers
of high-performance products in the metallurgical, nuclear energy, and
aerospace technologies. Beryllium is the only stable light metal with an
unusually high melting point; it also has a high modulus of elasticity,
low coefficient of thermal expansion, high stiffness-to-weight ratio, and
extreme hardness — properties frequently required by aerospace and pre-
cision instrument applications. Beryllium is also a good electrical and
thermal conductor. Because of its low atomic weight, beryllium has a high
permeability to x rays, and thin sheets of the metal are frequently used
as windows for x-ray tubes. Its low atomic weight, low thermal-neutron
-------
absorption cross section, and high melting point also make beryllium use-
ful as a structural component and moderator in certain nuclear reactors.
About one-fifth of the U.S. consumption of beryllium is in the form of
the metal.
When beryllium is added to copper and certain other metals, alloys
are formed which can be readily worked in the soft annealed state and.
which have, after further heat treatment, greatly improved strength,
hardness, durability, and resistance to fatigue. Approximately two-thirds
of the total beryllium consumed in the United States is used to produce
such alloys for the communications, computer, electronic, and electrical
industries.
Beryllium oxide is a colorless crystalline solid or an amorphous
white powder. It has an extremely high melting point, high thermal con-
ductivity, high electrical resistivity, and low thermal expansion. Pow-
dered beryllium oxide, easily compacted at temperatures well below its
melting point by sintering techniques, produces a ceramic material that
has great strength at elevated temperatures. About 10% of the annual U.S.
production of beryllium is consumed in such forms. They are used primar-
ily in nuclear reactor reflectors and moderators, high-voltage electrical
components, inertial guidance components, laser tubes, electronic ignition
systems, and resistor cores.
Beryllium is the smallest of the group II metals — the crystal radius
of the divalent ion is only 0.31 A. The small ionic radius and the result-
ant large surface charge density are dominant influences on the chemistry
of beryllium. Thus, beryllium forms stable compounds with small anions,
such as fluoride and oxide, because unusually close approaches to these
ion centers are possible. The highly hydrated state of the beryllium ion
in acid solution, the amphoteric nature of beryllium, and its tendency to
olation in basic media are all further consequences of the small size and
high surface charge density of the beryllium ion.
Beryllium and most of its compounds are among the most toxic and haz-
ardous nonradioactive substances currently used in industry. Exposure to
airborne beryllium products causes both acute and chronic inhalation ef-
fects; only intermetallic forms of beryllium, certain alloys of low beryl-
lium content, some low-grade minerals, and high-fired beryllium oxide show
little or no biologic activity. The carcinogenicity of beryllium and some
of its salts is also well established for rats and certain other animals,
but not man. No well-defined biochemical theory exists which explains the
above physiological effects. Tentative explanations of acute and chronic
beryllium poisoning are based on enzyme inhibition and on immune and nu-
cleic acid transcription mechanisms, but further research is needed to
establish the validity and the detailed biochemistry of the proposed
mechanisms.
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10
2.2 PHYSICAL AND CHEMICAL PROPERTIES
Although beryllium forms a large number of cationic and anionic com-
pounds with oxygen, fluorine, silicon, and related elements, only a few
forms of the element have commercial importance or environmental signifi-
cance; these include the metal, oxide, and hydroxide, which are produced
on an industrial scale (Heindl, 1970; Versar, Inc., 1975), various inter-
mediate forms, such as beryllium fluoride, ammonium fluoroberyllate, and
beryllium sulfate, and certain alloys and silicates. Pertinent physical
and chemical characteristics of these materials are discussed in the fol-
lowing sections.
2.2.1 Beryllium
Beryllium ranks 44th in abundance among the elements, constituting
about 0.0006% of the earth's crust (Weast, 1977); it is thus more abun-
dant than uranium (0.0004%) and some 12 times as plentiful as mercury
(0.00005%). Beryllium was discovered (as the oxide) by Vauquelin in 1798.
The metal was not isolated until 30 years later, when Wohler and then
Bussy, in independent researches, reduced beryllium chloride with potas-
sium metal.
In the older literature, beryllium is sometimes called glucinium or
glucinum (symbol Gl) because of the sweet taste of its salts; the name
beryllium was officially sanctioned by the International Union of Pure and
Applied Chemistry in 1957. The ChemLcal Abstracts identification number
for beryllium is 7440417.
2.2.1.1 Physical Properties — Refined beryllium is a brittle, steel gray
metal. It has several unique properties that make it attractive to de-
signers of high-performance products in the metallurgical, nuclear energy,
and space technologies. Beryllium is the only stable light metal with an
unusually high melting point; it also has extreme hardness, high stiffness-
to-weight ratio, a modulus of elasticity one-third greater than that of
steel, and minimal response to thermal fluctuations (Weast, 1977). Beryl-
lium has a high permeability to x rays, and thin sheets of the metal are
widely used as windows for x-ray tubes. Beryllium metal is a good elec-
tric and thermal conductor. Its low atomic weight, low thermal neutron
absorption cross section, and high melting point make it useful as a struc-
tural component and moderator for some nuclear reactors. Beryllium occurs
naturally only as the beryllium-9 nuclide; however, isotopes of mass 6
through 11 have been made and identified by various nuclear techniques
(Krejci and Scheel, 1966, p. 48). Normally occurring beryllium is a con-
venient and important source of neutrons which form when the element is
bombarded with alpha particles:
'fie + *He >• ^C + \n . (1)
The yield is about 30 neutrons per million alpha particles (Schwenzfeier,
1964, p. 451).
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11
Because of its highly dendritic structure and low ductility, cast
beryllium cracks and chips easily and is difficult to shape and machine
properly. Cast beryllium is converted to powder and hot-pressed to bil-
let form. The billets are readily machined to finished shapes. Billet
sections are rolled to sheet or extruded at 750°C to 790°C.
Numerical values for various physical properties of beryllium are
given in Table 2.1.
2.2.1.2 Chemical Properties — At ambient temperatures, beryllium is very
resistant to oxidation in air; polished surfaces of the pure metal remain
bright for years. At elevated temperatures, however, the metal becomes
very reactive, rapidly forming the oxide (BeO) at 850°C. The heat gener-
ated per gram of metal is greater than that for the oxidation of any other
metal; this property is the basis for the attractiveness of beryllium and
beryllium hydride propellants in high-performance rocket fuels (Back, 1970;
Robinson, 1973). Above 900°C, beryllium reacts with nitrogen and carbon
to form the nitride (Be3N2) and carbide (Be2C), respectively (Schwenzfeier,
1964, p. 452). Finely divided beryllium metal burns in air at about 550°C.
Beryllium is readily attacked by sulfuric and hydrochloric acids;
cold concentrated nitric acid has little effect, but dilute solutions re-
act slowly. Boiling alkalies dissolve beryllium with evolution of hydro-
gen. The resulting beryllium hydroxide is amphoteric. Beryllium reacts
with fused alkali halides — but not with fused alkaline earth halides —
liberating the alkali metal; halides of aluminum and heavier elements
are similarly reduced. Beryllium can be obtained from its halide salts
by reduction with any of the alkaline earth metals. However, poor yields
are obtained, except with magnesium, because of the formation of water-
insoluble fluoroberyllates.
Beryllium is the smallest of the group II metals — the crystal radius
of the divalent ion is only 0.31 A. Beryllium's ionic charge-to-radius
ratio (2/3°) is thus 6.45, similar to that for aluminum (6.0) and much
greater than that for the adjacent elements, magnesium (3.1), calcium
(2.0), strontium (1.8), barium (1.5), lithium (1.5), and sodium (1.0).
As a consequence, the chemistry of beryllium is very similar to that of
aluminum, and complete separation of these elements is difficult.
The small ionic radius of beryllium and the resultant large surface
charge density exert a dominating influence on the chemistry of beryllium.
For example, the most stable compounds are found with smaller anions, such
as fluoride (r = 1.36 A) and oxide (r = 1.40 A"), since unusually close
approaches to these ion centers by bivalent beryllium is possible. Indeed,
the oxide ion, with its high ratio of charge to radius, forms the most
stable bond of which beryllium is capable (Krejci and Scheel, 1966, p. 46).
In view of this circumstance, it is not surprising that bivalent beryllium
ion is the most heavily hydrated of all bivalent ions in aqueous solution
(Fricke and Schutzdeller, 1923; Spandau and Spandau, 1943). The high
charge-to-radius ratio of bivalent beryllium also accounts for the ampho-
teric nature of the ion (Basolo, 1956, p. 423; Cartledge, 1928) as well as
its strong tendency to hydrolyze (Section 2.2.4). In general, beryllium
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12
TABLE 2.1 PHYSICAL PROPERTIES OF BERYLLIUM
Property
Value
Atomic number
Atomic weight (12C = 12.000)
Atomic radius, kX
Atomic volume, cm3/mole, 25 °C
Electron configuration
First ionization potential, eV
Second ionization potential, eV
Ionic radius (Be2+), A
Electronegativity (Pauling's)
Thermal conductivity,
cal/(sec)(cm2)(°C/cm), 0-100°C
Density, g/cm3, 25 °C
Melting point, °C
Brinell hardness
Latent heat of fusion, kcal/mole
Mean specific heat, cal/(°C)(mole),
300-1300°K
Entropy, 52g8, cal/(°C)(mole)
Enthalpy, #298~#0> cal/mole
Vapor pressure, atm, 150-1550°K
Latent heat of evaporation, kcal/mole
Boiling point, °C
Electrical resistivity, yohm-cm
Electrochemical equivalent, mg/coulomb
Diamagnetic Hall coefficient
Optical properties
Sound conductance, m/sec
ft/sec
Emissivity, 650 nm
550 nm
Photoelectric work function, eV
Spin and parity
Magnetic dipole moment,
nuclear magnetons
Electric quadrupole moment,
cm2 x 10-21*
Binding energy of last neutron, MeV
Thermal-neutron cross section (Be9), mb
Crystal structure (a-beryllium)
4
9.01218
1.123
4.877
Ls22s2
9.320
18.206
0.31
1.5
0.349
1.8477 ± 0.0007
1287-1292 ± 3
60-125
2.8 ± 0.5
3.40 + (2.90 x 10~3)T
2.28 ± 0.02
465
log P = 6.186 + (1.454 x
- (16,734 ±
53.55
2970
4.31
0.04674
0.0024 ± 0.0001
Steel gray color, reflectivity
50-55%
12,600
41,300
Solid 0.61, liquid 0.61
Solid 0.61, liquid 0.81
3.92
3/2,-
-1.1774
0.02
1.664
6 ± 1.2
Hexagonal
a = 2.2810 ± 0.005 kX (2.2856 A)
a = 3.5760 ± 0.005 kX (3.5832 A)
a fa = 1.5677
Optical spectrum
Wavelength
(nm)
332.1343
332.1086
332.1013
313.1072
313.0416
265.0781
234.8610
Intensity
Arc
1000 ra
100
50
200
200
25
2000 Ra
Spark
30
150
200
50
r = narrow self—reversal; R = wide self-reversal.
Source: Adapted from Krejci and Scheel, 1966, Table 4.2, pp. 49-50.
Reprinted by permission of the publisher.
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13
is cationic in aqueous solutions at pH values lower than 5, forms insoluble
hydroxides or hydrated complexes at pH 5 to 8, and produces beryllate-like
complexes at pH values greater than 8. The entire process, from hydration
to formation of the beryllates, can be represented by the generalized
reaction
nBe
2+
nH20 = (BeOH)n
n+
(2)
which increases in extent as the pH of the solution increases (Everest,
1964, p. 8). The distribution of the different species in this system is
somewhat controversial. Early investigators concluded that Be3(OH)3 ,
Be2OH3+, and Be(OH)2 were the principal species present in solutions of
low beryllium concentration and moderate acidity (Kakihana and Sillen,
1956). Later workers concurred in the choice and importance of the first
two species but suggested that the third species was probably Be(OH)73
or Be6(OH)8*+, rather than Be(OH)2 (Mesmer and Baes, 1967). Their calcu-
lated distribution of the various hydrolysis products is shown as a func-
tion of temperature, concentration, and solution acidity in Figure 2.1^
Calculated thermodynamic quantities for the hydrolysis reactions at 25°C
are given in Table 2.2.
ORNL-DWG 77-4622
100
Figure 2.1. Calculated distribution of the beryllium species
Be3(OH)33+, Be2OH3+, and Bes(OH)73+. Dashed lines represent regions
where precipitation occurs. Source: Adapted from Mesmer and Baes,
1967, Figure 5, p. 1958. Reprinted by permission of the publisher.
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14
TABLE 2.2. CALCULATED THERMODYNAMIC QUANTITIES FOR
THE HYDROLYSIS REACTIONS AT 25°C
xBe2+ + z/H20 = Be (OH) (2a>#) + yH+
x y
Species AG° (kcal) AH° (kcal) AS0 (eu) AG ° (kcal)
Be2(OH)3+
Be 3 (OH) 3 3+
Be5(OH)73+
4.5
12.2
34.8
5.0
(4.4)a
16.0
(15.2)
45.3
1.4
(0.2)
15.3
(11.3)
35.2
-234.0
-430.6
-816.5
"Data in parentheses from B. Carell and A. Olin, Acta Chem.
Scand. 16:2357(1962).
Source: Adapted from Mesmer and Baes, 1967, Table IV, p. 1958.
Reprinted by permission of the publisher.
From the preceding discussion it is apparent that weak-acid salts of
beryllium are largely undissociated in aqueous solutions at a pH greater
than 5. This complication has discouraged research on these systems, and
relatively little work has been reported; consequently, it is not possible
to predict or interpret in detail the biochemical behavior of beryllium
with such physiologically important anions as phosphate, carbonate, ace-
tate, and amino acid complexes, especially at the pH of body fluids (Krejci
and Scheel, 1966, p. 50). However, an apparent behavioral trend seems
discernible. For example, under physiological conditions the removal of
hydrogen ion through the action of buffering agents normally present in
the living cell should shift the equilibrium of reaction (1) to the right,
forcing complete hydrolysis of the beryllium salt unless some other com-
plexing action is operative. Thus, a hydrolytic product or complex appears
to be the most probable ultimate form of physiologically active beryllium
(Krejci and Scheel, 1966, p. 56). This conclusion is supported by the work
of Veerkamp and Smits (1953), who attributed the reversal of alkaline phos-
phatase inhibition at increasing beryllium concentrations to precipitation
of beryllium hydroxide. It is also consistent with the observed fixation
of beryllium in soft tissues (Schepers, 1962) and with the very slow elim-
ination of beryllium from body tissues exposed to beryllium salts (Stokinger,
1972, p. 24); however, much additional research is required before the chem-
istry of beryllium in the biologic system can be definitively described.
2.2.1.3 Occurrence, Preparation, and Use — Beryllium does not occur in
the elementary state in nature (Latimer and Hildebrand, 1951, p. 60);
instead, it is found in some forty-odd mineralized forms (Table 2.3) which
are widely distributed in the earth's crust but which rarely exist in con-
centrations economically suitable for mining. The most important of these
minerals is beryl, a beryllium aluminum silicate which has the composition
3BeO»Al203»6Si02, and bertrandite, a hydrated disilicate which has the com-
position 4BeO»2Si02«H20. The latter has been mined commercially only since
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TABLE 2.3. BERYLLIUM MINERALS
Mineral
Barylite
Bertrandite
Beryl
Beryllonlte
Brommelllte
Chrysoberyl
Danalite
Euclase
Eudidymlte
Gadolinite
Hambergite
Helvite
Herderite
Kolbeckite
Leucophanlte
Mellphanlte
Milarite
Phenacite
Trlmerite
Source:
Chemical composition
Be2BaSi207
4BeO'Si02-H20
3BeC"Al203-6Si02
Na20'2BeO-P205
BeO
BeO-Al203
Fe, Zn, Be, Mn sulfosilicate
2BeO'Al203'2Si02-H20
Na2C"2BeO'6Si02-H20
2BeO'FeO'2Y203-2Si02
4BeO-B203'H20
Mn, Fe, Be sulfosilicate
CaO'CaFOH'2BeO-2P205
H, Be, P silicate
Ca, Na, Be fluosilicate
Ca, Na, Be fluosilicate
K20-4CaO-4BeO-Al203'24Si02-H20
2BeC"Si02
(Mn,- Ca)-Be-Si(\
Adapted from U.S. Department of
Crystal
system
Orthorhombic
Orthorhombic
Hexagonal .
Orthorhombic
Hexagonal
Orthorhombic
Isometric
Monoclinic
Monoclinic
Monoclinic
Orthorhombic
Isometric
Monoclinic
Monoclinic
Orthorhombic
Tetragonal
Monoclinic
Hexagonal
Monoclinic
the Interior,
Color
Colorless
Colorless, white,
or yellowish
Green, blue,
yellow, or white
Colorless, white,
or yellowish
White
Green
Flesh red or gray
Colorless, pale
green, blue, or
white
White
Black, greenish
black, or brown
Grayish white
Yellow, brown,
green, or
colorless
Yellowish or
greenish white
Blue or gray
Whitish green
or yellow
Yellow or red
Pale green
Colorless, white
yellow, rose,
or brown
Salmon pink
Hardness
6-7
6-7
7.5-8
5.5-6
9
8.5
5.5-6
7.5
6
6.5-7
7.5
6-6.5
5
3.5-4
4
5-5.5
5.5-6
7.5-8
6-7
Specific
gravity
4.0
2.6
2.6-2.8
2.8
3.0 ,
3.5-3.8
3.4
3.1
2.6
4.0-4.5
2.3
3.2-3.4
3.0
2.4
3.0
3.0
2.6
3.0
3.5 ...
Theoretical
BeO content
(%)
15
42
14
20
100
20
14
17
10
10
53
14
15
Variable
10
13
2
46
17
Beryllium
content
(%)
5.6
15.1
3.0-5.0
7.1
36.0
7.1
9
6.1
3.7
3.2-4.7
19.2
3.8-5.4
5.6-5.9
Up to 3.1
4.0
3.4-5.0
Up to 1.8
16.4
6.1
Type of
occurrence
Contact metamorphic
Granitic pegmatite
Granitic pegmatite
Granitic pegmatite
Contact metamorphic
Granitic pegmatite
Various
Granitic pegmatite
Nepheline syenite
Granitic pegmatite
Granitic and syenitic
Various
Granitic pegmatite
Hydrothermal
Syenitic pegmatite
Syenitic pegmatite
Granitic pegmatite
Granitic pegmatite
Contact metamorphic
1953, Table 1-1, p. 1-10.
-------
16
1969. Several processes are available for converting these minerals to
beryllium hydroxide, the intermediate from which all other beryllium prod-
ucts are made. The method currently used to process beryl is the Sawyer-
Kjellgren sulfate process. Until 1970, the Copaux-Kawecki fluoride process
was also used.
In the Copaux-Kawecki fluoride process, the pulverized ore is mixed
with sodium fluoroferrate(III), briquetted, roasted at 750°C, crushed, and
leached with water. The resulting solution consists principally of sodium
fluoroberyllate:
2Na3FeF6 + 3BeO»Al203«6Si02 >• 3Na2BeFA + Fe203 + A1203 + 6Si02 . (3)
The latter is heated with caustic soda to precipitate beryllium hydroxide,
which is filtered, washed, and calcined to the oxide:
Na2BeFz. + 2NaOH >• Be(OH)2 + 4NaF ,
heat (4)
Be(OH)2 > BeO + H20 .
The beryllium oxide is recovered in good yield (about 90%) with sufficient
purity to serve as an intermediate in the production of beryllium copper
and other alloys, but not elemental beryllium.
In the Sawyer-Kjellgren sulfate process the beryl ore is melted,
quenched with water, and reheated to 950°C. The resulting glass is pul-
verized, digested at 250°C with 85% sulfuric acid, and leached with water:
3BeO»Al203«6Si02 + 6H2SO<. >• 3BeSO<, + A12(SO<,)3 + 6Si02 + 6H20. (5)
The silica that is formed is removed by filtration, leaving a solution of
beryllium and aluminum sulfates. The latter is precipitated and removed
as alum after addition of ammonium hydroxide:
HaSOi, + Al2(SO/,)3 + 2NH<.OH + 22H20 > A12 (SOA)3» (NH/,) 2SO<,»24H20 . (6)
A chelating agent is supplied to hold iron impurities in solution, and
caustic soda is added; the resulting sodium beryllate solution yields
granular beryllium hydroxide on heating:
BeSOi, + 4NaOH »• Na2SO<, + Na2Be02 + 2H20 , (7)
Na2Be02 + 2H20 > 2NaOH + Be(OH)2 .
As in the Copaux-Kawecki process, beryllium oxide is obtained from the
hydroxide by calcination. The yield from the sulfate process (about 85%)
is slightly lower than that from the fluoride method, but product purity
is substantially better (Schwenzfeier, 1964, p. 458).
Although imported beryl ore continues to be an important source of
U.S.-produced beryllium hydroxide, an increasing fraction of the annual
total since 1969 is derived from native bertrandite ore. The technology
-------
17
used in this extraction is outlined in a Bureau of Mines information cir-
cular (U.S. Department of Interior, 1971). Pertinent details are also
available for an efficient solvent extraction technique for recovering
beryllium hydroxide from bertrandite ore, which has been extensively stud-
ied by the U.S. Bureau of Mines (U.S. Environmental Protection Agency,
1973a, p. 3-3). In the latter procedure, a liquor obtained by leaching
pulverized bertrandite ore with sulfuric acid is adjusted to pH 2, treated
with sodium hydrosulfide to convert trivalent iron to the nonextractable
divalent form, and extracted with a kerosene solution of di-2-ethylhexyl-
phosphoric acid (EHPA) :
0 0
ii ii
BeSO^(aq) + 2HOP (OR) 2 (org) -»• Be [OP (OR) 2] 2(org) + H2SO,.(aq) , (8)
where aq and org represent the aqueous solution and organic solvent ,
respectively.
In the United States, metallic beryllium is produced on a commercial
scale by reducing high-purity-beryllium fluoride with magnesium metal:
BeFa + Mg - >• Be + MgF2 . (9)
The operation is usually performed in an induct ion- type electric furnace
equipped with a graphite crucible. A stoichiometric excess of beryllium
fluoride is usually used because the reaction is strongly exothermic and
difficult to control (Heindl, 1970, p. 492). The beryllium fluoride
required in the reduction step is obtained by treating purified beryllium
oxide from the Copaux-Kawecki fluoride process or the Sawyer -Kjellgren
sulfate extraction process with ammonium bifluoride and thermally decom-
posing the resulting ammonium fluoroberyllate:
BeO + 2NH,,F»HF - >- (NHz,)2BeF4 + H20 ,
heat (10)
) 2NH<,F + BeF2 .
Alternatively, impure beryllium oxide can be used initially if the result-
ing ammonium fluoroberyllate is purified prior to the thermal dissociation
step.
Purification of scrap beryllium by electrorefining — to prepare flake -
is practiced in the United States and elsewhere. In this process, beryl-
lium oxide is first heated with carbon and chlorine gas at 1000 °C. The
reaction produces beryllium chloride and carbon dioxide:
1 000 °r
2BeO + 2C12 + C > 2BeCl2 + C02 . (11)
The vaporized beryllium chloride is collected by passing the effluent gases
through a condenser maintained at a temperature below 400°C. The beryl-
lium chloride is then mixed with 99 parts of anhydrous sodium chloride or
a lithium chloride-potassium chloride eutectic and electrolyzed at 400°C
or 500°C in a stainless steel cell equipped with an iron or nickel cathode
-------
18
and an annular anode basket containing the beryllium to be refined. An
electrical potential of 5 to 9 V is normally used. Good quality beryl-
lium metal flakes, which have a very low oxygen content, are produced.
Over 300,000 kg of beryllium was consumed industrially in the United
States in 1968 — about one-half in beryllium-copper alloys, nearly one-
third as beryllium metal, and the balance in other alloys and ceramics
(Heindl, 1970, p. 494). Almost all the metal is used in nuclear and aero-
space applications, where beryllium's low density, high modulus of elas-
ticity, high stiffness-to-weight ratio, high heat capacity, and low neutron
and x-ray absorption cross sections make it uniquely suitable as a struc-
tural component of orbiting satellites, missiles, aircraft brakes and rud-
ders, jet engine parts, special-purpose nuclear reactors, and x-ray tube
windows. The same properties also make beryllium metal attractive for use
in inertial guidance applications, space optics, ballistic missiles, and
other classified military uses (National Research Council, 1971, p. 10).
2.2.1.4 Biochemistry — Beryllium and most of its compounds are among the
most toxic and hazardous nonradioactive substances currently used in indus-
try (Berry, Osgood, and St. John, 1974, p. 87). Exposure to airborne beryl-
lium products causes both acute and chronic inhalation effects as well as
skin and conjunctival effects (U.S. Environmental Protection Agency, 1973i>);
only intermetallic forms of beryllium, certain alloys of low beryllium con-
tent, some low-grade minerals, and high-fired beryllium oxide show little
or no biologic activity. The carcinogenicity of beryllium compounds is
also well established for rats and certain other animals, but there is no
evidence to incriminate beryllium as a human carcinogen (Stokinger, 1972,
pp. 18-19).
No unified theory exists to explain the various physiological effects
described above — indeed, they may be due to various biochemical properties.
The biochemistry of beryllium is complex; because of its amphoteric nature
(Section 2.2.1.3), beryllium can exist as a cation, Be2+, or as an anion,
Be022~, each having a different toxicologic potential. Furthermore, at
physiologic pH, beryllium forms colloidal hydrates (Section 2.2.1.3). It
has a variable, and thus far only partially explored, capability to form
compounds with body proteins; some of the formed complexes are autoanti-
genic. Beryllium also alters phosphate metabolism by inhibition of sev-
eral enzymes and garbles nucleic acid transcription during cell division.
The relevance of these effects in the clinical toxicology of beryllium is
not fully understood at this time.
Beryllium enters the body chiefly by inhalation; little accumulation
or toxicity results from oral exposures because ingested forms of beryl-
lium are poorly absorbed through the intestinal wall (Aldridge, Barnes,
and Denz, 1949; Stokinger, 1972, pp. 22-23). Inhaled aerosols of soluble
beryllium salts hydrolyze to a colloidal form immediately on impingement
on the mucous surfaces of the bronchopulmonary tract. At low concentra-
tions this colloid appears to be mostly beryllium orthophosphate with small
amounts of the hydroxide admixed (Vorwald, Reeves, and Urban, 1966, p. 222).
Body proteins do not seem to be complexed under these conditions, although
adsorption and subsequent denaturation of proteins on the surface of col-
loidal beryllium phosphate appears probable.
-------
19
Some beryllium is retained in the lung for long periods; portions are
transported to and stored in all the major tissues of the body. The man-
ner in which this distribution occurs has been the subject of many inves-
tigations (Klemperer, Martin, and Liddy, 1952; Reeves and Vorwald, 1961;
Vacher and Stoner, 1968a, 1968£>); it seems to depend more on the extent
of exposure and the physiochemical state of the beryllium than on meta-
bolic differences of animal species (Browning, 1969, p. 69; Stokinger,
1972, p. 24; Vacher, Deraedt, and Benzoni, 1973). When small doses of
soluble beryllium salts are administered to rats by inhalation, beryllium
appears in the blood plasma as a soluble diffusible complex of an organic
acid, chiefly citrate, which tends to be deposited in the kidney and bone
or excreted in the urine; in larger concentrations, beryllium combines
with plasma phosphates to form nondiffusible, insoluble particulate aggre-
gates, which are bound to plasma globulin, such as gamma globulin (Tepper,
1972
-------
20
severity of response to beryllium in the rat (Clary, Bland, and Stokinger,
1975). The salient features of the lysosomal theory are outlined in the
right portion of Figure 2.2. Other researchers attribute chronic berylli-
osis to a delayed hypersensitivity reaction to which auto immunity develops
(Deodhar, Barna, and Van Ordstrand, 1973; Hanifin, Epstein, and Cline, 1970;
Naeye, 1973; Sterner and Eisenbud, 1951; Vacher, 1972). A generalized mech-
anism for this approach is diagrammed in the left portion of Figure 2.2.
There appears to be little reason to doubt involvement of the adrenal func-
tion in chronic berylliosis, but details of its participation and the rela-
tive importance of the proposed lysosomal and immunological mechanisms are
matters that must be resolved by additional research (Stokinger, 1972,
p. 30; Tepper, 1972&, p. 133; Vorwald, Reeves, and Urban, 1966).
ORNL-OWG 77-4514A
BERYLLIUM INHALATION
BERYLLIUM
SENSITIVITY
BERYLLIUM BODY TRANSPORT
BERYLLIUM STORAGE
(LUNG. BONE, LIVER. LYMPH NODES, ETC.)
(1 TO 15 YEARS) •
TRIGGERING MECHANISM
(PREGNANCY, SURGERY, ETC.)
ALTERED ADRENAL FUNCTION
RELEASED OR REDISTRIBUTED
BERYLLIUM
(t)
(21
IMMUNE REACTION
CELL-WALL LESIONS
BERYLLIUM-LYSOSOME COMPLEX
LYSOSOME INSTABILITY
DESTRUCTIVE ENZYME RELEASE
CELL-WALL LESIONS
CHRONIC BERYLLIUM DISEASE
(t) - IMMUNE MECHANISM
(2) = LYSOSOME MECHANISM
Figure 2.2. Two possible chronic beryllium disease mechanisms.
Source: Adapted from Hurlbut, 1974a, Figure 1, p. 13.
-------
21
2.2.2 Beryllium Oxide (Beryllia)
Beryllium oxide (BeO) is an important chemical intermediate resulting
from the extraction of beryllium from beryl or bertrandite (Section 2.2.1.3).
Beryllium oxide is also known as beryllia; its Chemical Abstracts identifi-
cation number is 1304569.
2.2.2.1 Physical Properties — Beryllium oxide is a colorless crystalline
solid or an amorphous white powder. It has a molecular weight of 25.01,
a hardness of 9 (Mohs scale), and a density of 2.86 to 3.02, depending on
the method of preparation (International Agency for Research on Cancer,
1972, pp. 17-18). Beryllium oxide is soluble in acids and alkalis but is
essentially insoluble in water (0.7 ug per 100 ml) (Dutra and Largent,
1950). Beryllium oxide melts near 2530°C (Weast, 1977), but it can be
compacted to a coherent mass at much lower temperatures by sintering tech-
niques. Beryllium oxide has the highest thermal conductivity of any metal
oxide — higher than that of some metals, including beryllium itself (Krejci
and Scheel, 1966, p. 77). Beryllium oxide also has low compressibility,
low thermal expansion, and exceptionally high electrical resistivity. Other
physical properties are shown in Table 2.4.
2.2.2.2 Chemical Properties — Because of the strong binding forces and
short bond distances between beryllium and oxygen ions in the crystal lat-
tice, beryllium oxide is inherently an extremely stable compound. Its
vapor pressure is negligibly low up to 2000°C (Erway and Seifert, 1951).
Above 1200°C, however, it is readily attacked by water vapor to form gas-
eous beryllium hydroxide:
BeO + H20 >1200°Ci Be(OH)2 . (12)
Sintered beryllium oxide is also seriously corroded by gaseous hydrogen
fluoride; the other gaseous halogens and volatile chlorides react with
beryllium oxide only when it is finely divided. Liquid reagents, such as
fused carbonates, fluorides, and pyrosulfates, and aqueous solutions, such
as the alkali hydroxides and mineral acids, attack finely divided beryl-
lium oxide, but not the sintered form. Among liquid reagents, the sin-
tered form is susceptible only to fused alkalis. Sintered beryllium oxide
is also essentially stable to all molten metals, except calcium (Krejci
and Scheel, 1966, p. 78).
2.2.2.3 Preparation and Use — Beryllium oxide is usually prepared by
calcining the hydroxide (Section 2.2.1.3), but it can also be obtained
by heating the sulfate, nitrate, basic carbonate, or other compounds in
which beryllium is the only element forming a nonvolatile oxide. Direct
formation of the oxide from the metal is difficult because of the high
ignition temperature required and the cohesive nature of the resulting
oxide film, which protects the bulk of the metal from further oxidation.
The chemical and physiological reactivity of the resulting oxide depends
on the ignition temperature — the lower the temperature, the greater the
surface area and chemical or biological reactivity of the resulting oxide.
For example, beryllium oxide ignited at 400°C to 500°C is readily soluble
in acids and alkalis, but if heated to 1000°C it dissolves only in hydro-
fluoric acid or hot concentrated sulfuric acid (Novoselova and Batsanova,
-------
22
TABLE 2.4. PHYSICAL PROPERTIES OF BERYLLIUM OXIDE (BERYLLIA)
Property
Value
Formula
Molecular weight
Crystal structure, 26°C
Density, g/cm3, 26°C
Melting point,°C
Boiling point,°C
Heat of formation,
kcal/mole
Entropy of formation, ASf298»
cal/(°C)(mole)
Free energy of formation,
kcal/mole
Equilibrium constant
Dissociation energy, kcal/mole
Reaction of metallic Be with 02,
750-950°C
Energy of activation, B,
kcal/mole
Entropy of activation, AS*,
cal/(°C)(mole)
Specific heat, cal/(°C)(mole)
0°K
73°K
173°K
273°K
300 °K
500°K
700°K
900°K
1200°K
Enthalpy
UT - #273» cal/mole, 373-1173°K
By - #298» joules/mole
363-1128°K
HT - ff298> cal/mole 1200-2820°K
Entropy
5298, cal/(°C)(mole) 298°K
ST - 5298. cal/(°C)(mole)
400°K
600°K
800° K
1000° K
1200°K
Thermal conductivity,
cal/(sec)(cm2)(°C/cm)
-253°C
-160°C
0°C
725° C
1825°C
Coefficient of expansion,
cm/(cra)(0C)
20- 300° C
20-600° C
20-1200° C
20-1800° C
Magnetic susceptibility,
cgs units, 24. 8° C
BeO
25.01
Hexagonal
a = 2.698 A, a = 4.380 A
3.008 (x ray)
2550 ± 30
3960 ± 200 (estimated)
-143.1
-23.43
-136.12
10101.88
106 ± 3
50.3
-10
0
0.3
2.6
5.5
6.146
9.308
10.700
11.499
12.296
11.1084T + (7.1245 x
+ (8.40705 x
- (5.31245 x 107)r~2
- 5453.21
36.36T + (7.56 x 10~3)r2
+ (1.36 x lO6)?-1 - 1600
9.71T + (1.045 x 10~3)T2 - 3540
3.37 ± 0.05
2.089
5.807
8.872
11.433
12.630
0.04
1.75 (maximum)
0.8
0.111
0.035 (minimum)
6.6 x 10~6
7.2 x KT6
9.5 x 10~6
9.8 x KT6
-11.93 x 10-6
Source: Adapted from Krejci and Scheel, 1966, Table 4.2, pp. 49-50.
Reprinted by permission of the publisher.
-------
23
1968, p. 7). Similarly, after intratracheal instillation, oxide prepared
at 500°C is quickly distributed to the liver, kidneys, and bones of rats,
while oxide calcined at 1600°C remains largely in the lungs (Spencer et
al., 1965).
Although most beryllium oxide produced in the United States is con-
sumed in manufacturing beryllium-copper alloys or beryllium metal, a small
fraction of the total — 10% in 1974 — is used to produce sintered beryl-
lium oxide ceramic products (U.S. Environmental Protection Agency, 1973a,
p. 3-22). In a typical ceramic manufacturing process, the raw beryllium
oxide is ground in a ball mill, screened to size, spray dried, mixed with
binding agents, extruded through an appropriately shaped die, and sintered
(U.S. Environmental Protection Agency, 1973a). A block diagram of this
manufacturing sequence is shown in Figure 2.3. Emissions from such an
operation are almost entirely in the form of dusts, fumes, and mists, which
contain low-fired beryllium oxide. The source and nature of these emissions
are shown in Table 2.5.
Almost all the present uses of beryllium oxide are related to its low
neutron absorption cross section, high melting point, low thermal expansion,
high heat conductance, high electrical resistivity, and general compati-
bility with corrosive environments at elevated temperatures; these prop-
erties make it valuable for use in nuclear reactor fuels and moderators,
high-voltage electrical components, inertial guidance components, laser
tubes, electronic ignition systems, and resistor cores (U.S. Environmental
Protection Agency, 1973a). In addition, the superior microwave transmis-
sion characteristics of beryllium oxide make it essential for certain appli-
cations, such as radomes and microwave windows (Heindl, 1970, p. 495).
Beryllium oxide is also used in limited quantities as a catalyst for certain
organic chemical reactions (Durocher, 1969, p. 65).
2.2.3 Beryllium Sulfate
Beryllium sulfate most frequently occurs as the tetrahydrate,
BeSOi,«4H20, which is obtained by evaporating beryllium oxide, hydroxide,
or carbonate in dilute sulfuric acid. It is a colorless crystalline com-
pound. Its molecular weight is 177.14, and the Chemical Abstracts identi-
fication number is 7787566. The tetrahydrate is soluble in water (Table
2.6) but insoluble in ethanol; its solubility in water is strongly depressed
by the presence of sulfuric acid. Like other soluble beryllium salts,
the sulfate is extensively hydrolyzed in aqueous solution (Table 2.7),
and the resulting liquid is strongly acidic (Table 2.8):
BeSOA + 2H20 < > Be(OH)2 + 2H+ + SO,.2" (13)
The hydrolysis constant for the reaction is 1.4 x 10~7 (Novoselova and
Batsanova, 1968, p. 12). In this equilibrium, the degree of hydrolysis
is governed by the hydrogen ion concentration — if the hydrogen ion is
removed by any mechanism, complete hydrolysis of the beryllium sulfate
occurs. This characteristic behavior of the beryllium ion has serious
physiological consequences. In the living cell, excess free hydrogen ions
-------
24
ORNL-DWG 77-4617R
RECEIVING
Bed
0.4-0.75 Urn
WATER
POLYVINYL ALCOHOL
POLYVINYL GLYCOL
WET MILL TO
40-100 nm
SCREENING
(200 MESH)
SPRAY DRYING
80°C
DRY SCREENING
FERRO FILTER
FORMING
DEDUSTED.
VIBRATED
ADD BINDERS
AND MIX
FOR EXTRUSION
GRADE BeO
EXTRUSION
SINTERING
INSPECTION
GRINDING,
MACHINING
Figure 2.3. Manufacture of beryllium oxide ceramic products.
Source: Adapted from U.S. Environmental Protection Agency, 1973a,
Figure 3-14, p. 3-23.
-------
25
TABLE 2.5. SOURCES OF BERYLLIUM CERAMIC
PLANT EMISSIONS
Source Emissions
Spray dryer Water
Beryllium oxide
Dry boxes Beryllium oxide
Kilns Beryllium oxide
Binders
Water
Machining Beryllium oxide
Binders
Water
Cutting fluids
Development laboratory Traces of acids
Beryllium oxide
Binders
Source: U.S. Environmental Protection
Agency, 1973a, Table 3-5, p. 3-24.
TABLE 2.6. SOLUBILITY OF BERYLLIUM SULFATE
TETRAHYDRATE IN WATER
Temperature (°C)
25
50
75
85
95
Solubility
(g per 100 g of solution)
29.32
32.93
37.98
41.33
43.45
Source: Novoselova and Batsanova, 1968, page
12.
TABLE 2.7. DEGREE OF HYDROLYSIS OF
BERYLLIUM SULFATE SOLUTIONS AT 25°C
Concentration of Degree of
BeS04 (M) hydrolysis, a
0.8636 0.736
0.5757 0.639
0.2879 0.619
0.1079 0.712
Source: Adapted from Novoselova and
Batsanova, 1968, p. 13.
-------
26
TABLE 2.8. ACIDITY OF BERYLLIUM SULFATE
SOLUTIONS AT 20°C
Concentration Concentration
of BeSO^ (M) ptl of BeSOt, (Af) pH
1
0.5
0.2
0.1
1.88
2.24
2.62
2.80
0.05
0.02
0.01
3.08
3.78
3.61
Source: Novoselova and Batsanova, 1968, p. 13.
are systematically removed by the buffering action of proteins, bicarbon-
ate ion, phosphate salts, or organic acids. Consequently, soluble beryl-
lium salts in this environment tend to be converted completely to insoluble
hydrolytic products, which have extremely long residence times (Krejci and
Scheel, 1966, p. 56). Under favorable circumstances, however, precipita-
tion of the hydroxide may be reduced or prevented if the soluble beryllium
salt reacts first with a chelating agent, such as citric or oxalic acid.
Addition of alkali to a solution of beryllium sulfate causes the pre-
cipitation, beginning at pH 5.7, of a basic salt in which the mole ratio of
alkali to beryllium sulfate is 1.8; initially, sulfate ions are retained
in the precipitate, but they are gradually displaced by hydroxyl ions as
more alkali is added. Precipitation is complete at pH 6.5, and addition
of more alkali causes the precipitate to redissolve. Solutions of beryl-
lium sulfate and other soluble salts readily dissolve beryllium oxide or
hydroxide. This behavior reflects the formation of hydroxo complexes with
Be-OH-Be bridges (Cotton and Wilkinson, 1962, p. 174).
When heated, beryllium sulfate tetrahydrate loses 2 moles of water at
92°C and 4 moles of water at 250°C (International Agency for Research of
Cancer, 1972, p. 18). The resulting anhydrous beryllium sulfate dissolves
only slowly in cold water; it is also less stable to heat than other alka-
line earth sulfates, because of the strong polarizing effect of the small
bivalent beryllium ion, which deforms the sulfate ion and weakens its sulfur-
oxygen bonds. As a result, about 4% of the contained sulfur is evolved as
sulfur trioxide when beryllium sulfate is heated to 600°C for 1 hr (Everest,
1964, p. 25).
Beryllium sulfate is the pure intermediate in the production of beryl-
lium oxide, representing 10% of total beryllium usage. It is also occa-
sionally used in the laboratory when a soluble beryllium salt is required.
-------
27
2.2.4 Beryllium Hydroxide
Beryllium hydroxide is an important intermediate in all the currently
used methods of recovering beryllium from its ores (Section 2.2.1.2); it
is also important physiologically because of its formation and retention
in various tissues under biologic conditions. The nominal formula and
molecular weight of the compound are Be(OH)2 and 43.03. The Chemical
Abstracts identification number is 13327327.
Beryllium hydroxide occurs in several forms. When prepared from stoi
chiometric quantities of ammonium hydroxide and dilute aqueous beryllium
salts at pH 5.7, beryllium hydroxide is an amorphous hydrate, Be(OH)2»a;H20.
On standing, this material is transformed into a metastable crystalline
form, a-Be(OH)2. The latter, in turn, changes slowly into a stable crys-
talline 3 modification. The last conversion is accelerated by contacting
the a form with an alkali solution (Everest, 1964, p. 12; Novoselova and
Batsanova, 1968, p. 4). The stable $-beryllium hydroxide is obtained
directly by treating beryllium sulfate with sodium hydroxide.
The solubility of the hydroxide decreases progressively on passing
from the amorphous product to the 6 form. The solubility of crystalline
a-beryllium hydroxide in water is less than 10"7 mole per liter (Gilbert
and Garrett, 1956). The solubility product constant for beryllium hydrox-
ide in water has been determined by several different investigators, but
divergent results differing by several orders of magnitude were obtained,
and no consensus exists (Gilbert and Garrett, 1956; Korenman, Frum, and
Tsygankova, 1956; Kovalenko and Geiderovich, 1959).
The behavior of beryllium hydroxide in alkaline media is not well
established. Early workers produced stable polynuclear beryllium oxide
hydrosols in low concentrations of strongly coordinating anions and be-
lieved that similar olated complexes were formed when beryllium hydrox-
ide is dissolved in alkali (Everest, 1964, p. 14). However, the data of
Baes and Mesmer (1974, p. 96) only support the presence of mononuclear
species in such solutions. The latter workers suggest that Be(OH)3~ and
Be (OH)/,2" are the dominant species in aqueous solutions saturated with
a-Be(OH)2 in the pH range 9 to 13. These species appear to result from
the following reactions:
a-Be(OH)2 + H20 = Be(OH)3~ + H+ ,
a-Be(OH)2 + 2H20 = Be(OH)42~ + 2H+ .
When heated, hydrated beryllium hydroxide loses water and is converted
first to the anhydrous form, then to the oxide. The temperatures at which
these changes occur depend on the manner in which the material was prepared.
Typically, dehydration occurs at 150°C to 180°C, dissociation begins at
240°C to 300°C, and all but the last traces of water are removed at 500°C
(Novoselova and Batsanova, 1968, p. 7).
Unlike the alkali hydroxides, beryllium hydroxide does not absorb car-
bon dioxide. Neither is it soluble in cold solutions of ammonium salts or
of most amines, except ethylenediamine (Sidgwick, 1950, p. 202).
-------
28
2.2.5 Beryllium Halides and the Fluoroberyllates
The fluoride BeF2 is the most important beryllium halide; it has impor-
tant applications in the preparation of metallic beryllium (Section 2.2.1.3),
in the molten salt nuclear reactor, and in analytical chemistry (Novoselova
and Batsanova, 1968, p. 18). The Chemical Abstracts identification number
of this compound is 7787497. In the anhydrous state, beryllium fluoride is
normally a glassy, hygroscopic substance. It has a molecular weight of
47.01 and a density of 1.986 (25°C). The glassy material has no definite
melting point but softens near 800°C with sublimation (Stecher, 1968).
Crystalline BeF2 , which can be prepared from the glassy form by careful
thermal treatment, melts near 550°C. The molten salt is a poor conductor
of electricity. Beryllium fluoride is freely soluble in water, 18 g-moles
per liter dissolving at 25°C; however, it is only sparingly soluble in
ethanol and is insoluble in anhydrous hydrogen fluoride. Other properties
of beryllium fluoride are given in Table 2.9. Beryllium ion bonds almost
as strongly with fluoride as with oxide ions — accordingly, aqueous solu-
tions of beryllium fluoride are only about 1% hydrolyzed and are less acidic
than corresponding concentrations of other beryllium salts (Table 2.10).
Beryllium fluoride is prepared commercially by thermally decomposing the
ammonium fluoroberyllate salt, (NH/, ) 2BeF<, , at 240°C or higher (Section
2.2.1.2). It cannot be formed by treating the hydroxide with aqueous hydro-
fluoric acid, as the resulting salt, BeF2»4H20, hydrolyzes when heated.
Beryllium fluoride readily coordinates with the fluorides of alkali or
alkaline earth metals to form compounds of the types Ml2BeFi, and MUBeF,,:
BeF2 + 2MF - >- M2BeF4 ,
(15)
BeF2 + MF2 -
These compounds contain the fluoroberyllate ion, BeF<,2~, in which the fluo-
rine atoms are tetrahedrally arranged around the beryllium atom in the crys
tal lattice. The alkali metal complexes are quite stable and dissolve in
water without decomposition (Table 2.11). The alkaline earth fluoroberyl-
lates are only sparingly soluble in water; 100 g of calcium fluoroberyllate
solution contains 0.0125 g of salt at 25 °C, and solutions of the barium
compound contain even less (Novoselova and Batsanova, 1968, p. 21). The
Ml2BeFi, and MHBeF<, fluoroberyllates are isomorphous with the sulfates of
the corresponding metals — except for the lithium and sodium salts — and
have similar physical and chemical properties. The fluoroberyllates also
bear a strong structural resemblance to silicates, a factor that led to the
production of unique fluoroberyllate glasses having low dispersion and a
wide transmission range (Krejci and Scheel, 1966, p. 71).
Beryllium chloride, BeCl2, is a colorless crystalline compound. It
has a molecular weight of 79.92 and a density of 1.899 (25°C) . The Chem-
ical Abstracts identification number is 7787475 (Weast, 1977). The melting
points reported for anhydrous beryllium chloride vary widely because of
the strong tendency of the salt to supercool; they fall into two groups,
one near 404°C, the other near 425°C. A similar uncertainty exists with
boiling point determinations of the salt, which vary from 482. 5°C to 510°C
-------
TABLE 2.9. PROPERTIES OF THE BERYLLIUM HALIDES
Property
Formula
Molecular weight
Melting point
Boiling point
Heat of formation, Afly298> kcal/mole
Gas
Crystalline
Entropy, S^ga, cal/(°C) (mole) , gas
Heat of vaporization, Aff , kcal/mole
vap
Entropy of vaporization, A5 , cal/(°C) (mole)
Heat of sublimation, Aff , kcal/mole
Entropy of sublimation, AS , cal/ (°C) (mole)
Beryllium fluoride
BeF2
47.01
(See text)
Sublimes
-191.3 ± 2.0 (2nd law)
-191.2 ± 0.4 (3rd law)
-241.2 ± 0.8
(cristobalite)
54.4 ± 0.3
53.25 ± 0.25-
(550 - 950°C)
38.7 + 0.6
(550 - 950°C)
Beryllium chloride
BeCl2
79.93
(See text)
(See text)
-118.03 ± 0.56
-118.25
26.24
(573 - 733°C)
573 - 753°K 30.84
440 - 600 °K 32.9 ± 0.4 (2nd law)
298°K 33.1 ± 0.5
440 - 600 °K 32.1 (3rd law)
440 - 600 °K 42.7 ± 1.4 (2nd law)
298°K 43.2 ± 1.5
Beryllium
bromide
BeBr2
168.85
490 °C
488 ± 2°C
Sublimes
-86.7
22
Beryllium
iodide
BeI2
262.85
510 °C
480 ± 4°C
Sublimes
-54.3
19
VD
Source: Adapted from Krejci and Scheel, 1966, Table 4.2, pp. 49-50. Reprinted by permission of the publisher.
-------
30
TABLE 2.10. ACIDITY OF AQUEOUS BERYLLIUM FLUORIDE
SOLUTIONS AS A FUNCTION OF CONCENTRATION
Concentration of
BeF2 (AO
0.10
0.25
0.45
PH
4.55
4.25
3.96
Concentration of
BeF2 (M)
0.60
0.70
1.00
PH
3.71
3.59
3.55
Source: Novoselova and Batsanova, 1968, p. 18.
TABLE 2.11. SOLUBILITY OF ALKALI FLUOROBERYLLATES
AT 25°C
Fluoroberyllate
Ammonium
Monoammonium
Sodium, 20 °C
Potassium
Rubidium
Cesium
Formula
(NHit)2BeFi+
NH^BeFs
Na2BeFi+
K2BeFi,
Rb2BeFtf
Cs2BeFit
Solubility (%)
32.3
54.2
1.45
1.52
10.22
56.76
Source: Adapted from Novoselova and Batsanova,
1968, p. 21.
(Krejci and Scheel, 1966, p. 70). Anhydrous beryllium chloride is very
soluble in water (Table 2.12), ethanol, and ether but is insoluble in non-
donor solvents such as benzene, carbon tetrachloride, and chloroform.
Beryllium chloride is more strongly hydrolyzed in aqueous solution than
the fluoride — 4.6% for a 0.1 N solution — since the larger chloride ion
competes less effectively for the beryllium ion than its smaller congener;
the hydrolysis constant for the reaction
2BeCla + 2H20 < > Be2(OH)a2"1" + 2HC1 + 2C1" (16)
is 1.6 x 10~7 (Gilbert and Garrett, 1956). The resulting solution is
accordingly more acidic than a similar fluoride solution (Table 2.13).
Unlike beryllium fluoride, the chloride does not readily form anionic
chloro complexes in aqueous solution (Everest, 1964, p. 52). Anhydrous
-------
31
TABLE 2.12. SOLUBILITY OF BERYLLIUM
CHLORIDE IN WATER
Temperature (°C)
Solubility
(g BeCl2 per 100 g of solution)
0
20
30
40
40.35
42.24
43.52
44.12
Source: Novoselova and Batsanova, 1968, p. 16.
TABLE 2.13. ACIDITY OF AQUEOUS BERYLLIUM CHLORIDE
SOLUTIONS AS A FUNCTION OF CONCENTRATION
Concentration of
BeCl2 (M)
pH
Concentration of
BeCl2 (M)
1
0.5
0.2
0.1
1.27
1.85
2.41
2.76
0.005
0.002
0.001
3.07
3.40
3.65
Source: Novoselova and Batsanova, 1968, p. 16.
beryllium chloride strongly resembles aluminum chloride in its ability to
catalyze organic syntheses. It is nearly but not quite as efficient
(Sidgwick, 1950, p. 204). Anhydrous fused beryllium chloride is a poor
electrical conductor, but small amounts of alkali metal fluorides con-
siderably improve this property, evidently by the formation of chloro-
beryllates (Schmidt, 1926). Anhydrous beryllium chloride forms numerous
complexes of the type BeCl2X2, where X represents a wide variety of neu-
tral organic ligands. Examples of such complexes, which can be prepared
either by direct interaction or by addition of the ligand to an ether solu-
tion of beryllium chloride, include diethyl ether, pyridine, acetone,
nitriles, aldehydes, quinoline, aliphatic amines, piperidine, thiourea,
and tetrahydrofuran. Usually the stoichiometry of the complexes involves
two ligands per atom of beryllium, though some departures from this ratio
occur (Everest, 1964, p. 55). Beryllium chloride is prepared on a com-
mercial scale by passing chlorine over a mixture of beryllium oxide and
carbon heated to about 1000°C (Section 2.2.1.3). The product is hygro-
scopic and must be kept dry to prevent deterioration by hydrolysis. Small
-------
32
quantities of the chloride are consumed in the United States for electro-
refining beryllium metal scrap.
The preparation and chemical reactions of beryllium bromide and iodide
are similar to those described for the chloride, except that hydrolysis
becomes more pronounced with increasing anion radius — the anhydrous iodide
reacts violently with water, releasing hydrogen iodide (Stecher, 1968).
These compounds are seldom used, except for research. Some of their pub-
lished physical properties are tabulated in Table 2.9.
2.2.6 Beryllium Alloys
When beryllium is added to copper and certain other metals, alloys
are formed which can be readily worked in the soft annealed state and which
have, after heat treatment, greatly improved strength, hardness, durability,
and resistance to fatigue. Approximately half the total beryllium consumed
in the United States in 1970 was used for beryllium-copper alloys needed
primarily in communications, computer, electronic, and electrical equip-
ment (Heindl, 1970, pp. 489, 494). The most important alloy of this group
contains cobalt as well as beryllium and copper; the cobalt helps to con-
trol the grain size during casting and the subsequent heat treatment
response. The composition commonly used for this alloy is 1.9% to 2.05%
beryllium, about 0.25% cobalt, and the balance copper (Schwenzfeier, 1964,
p. 465). The extraordinary contrast in the physical properties of this
alloy before and after heat treatment is shown in Table 2.14.
Although alloys can be formed by melting together appropriate quanti-
ties of the separate metals, this procedure is not followed in the commer-
cial production of beryllium-copper alloys because of the high cost of
producing pure beryllium metal; instead, these alloys are made by directly
reducing beryllium oxide with carbon in the presence of molten copper
(Schwenzfeier, 1964, p. 466). The reduction is usually performed in a
TABLE 2.1A. PHYSICAL PROPERTIES OF BERYLLIUM COPPER No. 25 STRIP BEFORE AND AFTER HEAT TREATMENT
Heat
Temper treatment
A
1/4 H
1/2 H
H
AT 3 hr, 600 "F
1/4 HT 2 hr, 600°F
1/2 HT 2 hr, 600 °F
HT 2 hr, 600 "F
Tensile
strength
(psi)
60-78,000
75-88,000
85-100,000
100-120,000
165-190,000
175-200,000
185-210,000
190-215,000
Proportional
limit
(psi)
15-20,000
40-60,000
55-70,000
70-85,000
100-125,000
110-135,000
120-145,000
125-155,000
Yield
strength,
0.2Z offset
(psi)
28-36,000
60-80,000
75-90,000
90-112,000
140-175,000
150-185,000
160-195,000
165-205,000
Fatigue
strength
Rockwell (psi) fc
5 hardness (108 load cycles) o
35-60
10-35
5-25
2-8
4-10
3-6
2-5
1-4
30T46-67
30T62-75
30T74-79
30T79-83
30N56-61
30N58-63
30N59-65
30N60-66
30-35,000
31-36,000
32-38,000
35-39,000
34-38,000
35-39,000
39-43,000
41-46,000
17-19
16-18
15-17
15-17
22-25
22-25
22-25
22-25
Elongation in 2 in., Z.
Electrical conductivity, percent of International Annealed Copper Standard.
Source: Adapted from Schwenzfeier, 1964, Table 7, p. 466. Reprinted by permission of the publisher.
-------
33
carbon-lined electric arc furnace equipped with graphite electrodes, such
as that shown in Figure 2.4. The reaction temperature is maintained
between 1800°C and 2000°C; part of the beryllium oxide is reduced to beryl-
lium. The following reaction probably occurs:
BeO(s) + C(s)
Be(d) + C0(g)
(17)
where s indicates the solid phase; d, dissolution in molten copper; and g,
the gas phase. A flowsheet of the production process is shown in Figure
2.5. The finished beryllium-copper ingots, which usually contain about
4% beryllium, are subsequently remelted with copper chips to produce the
finished 2% beryllium alloy stock forms (U.S. Environmental Protection
Agency, 1973c, p. 3-9).
ORNL-OWG 77-4619
Bus bar
\
Beryllium
oxide brickA
r-
£
0
0
0
/
/
£
m
%
/
st>
Mix
a
i
>• •
/• •
3atr
>
fi
-
r
Vater- cooled steel electrode holder
x Water -cooled copper electrode lip
f .-Water-cooled furnace top
/ Beryllium oxide
f" pouring spout
— * — ' — ! 3
' f '-- *%£
''^Z^i.
Mix
f c
4^9 r-m
\
f
, — • —
*•
Carbon
" bfichs
Carbon-black
^ insulation
_ Graphite
" electrode
Steel
^-~ furnace
shell
Figure 2.4. An arc furnace used in preparing beryllium copper.
Source: Adapted from Schwenzfeier, 1964, Figure 1, p. 467. Reprinted
by permission of the publisher.
Other alloys of beryllium are also used, although on a greatly re-
duced scale compared with copper. Nickel containing up to 2.6% beryllium
is heat treatable and has strengths similar to those of the stronger stain-
less steels. Castings of this alloy are used in the glass industry as
plungers, molds, and neck rings. Wrought forms of beryllium-nickel are
about 20% stronger than cast forms and are attractive for use as instru-
ment springs, diaphragms, and mechanical fasteners. The addition of 0.1%
to 0.5% beryllium to aluminum results in an alloy with improved fluidity
-------
34
ORNL-DWG 77-4578A
IMPURE
BERYLLIUM-COPPER
ALLOY
PURIFICATION OF ALLOY
BY COOLING AND SKIMMING
IN FOUNDRY CRUCIBLE
CASTING TABLE
FINISHED
BERYLLIUM-COPPER
INGOTS
Figure 2.5. Flowsheet for the production of beryllium copper from
beryllium oxide. Source: Adapted from Schwenzfeier, 1964, Figure 2,
p. 468. Reprinted by permission of the publisher.
-------
35
and grain structure which is useful for polished castings such as cook-
ware. Beryllium-iron alloys have coarse grain structures generally unsuit-
able for commercial applications, but beryllium steels containing nickel
and chromium have exceptionally high strengths and hardness at high tem-
peratures. The latter may be used when special properties not producible
with carbon are desired (Schwenzfeier, 1964, p. 469). Beryllium alloys
are discussed further in surveys by the U.S. Department of the Interior
(1953), Schwenzfeier (1964), and Ricksecker (1965).
2.2.7 Beryllides
Beryllium forms intermetallic compounds — beryllides — with a variety
of metals (Table 2.15), some of which have unusual combinations of physical,
mechanical, thermal, and electrical properties. Several beryllides that
have excellent resistance to oxidation, high strength at elevated tempera-
tures, good thermal conductivity, low density, and good hardness, compared
with refractory metals and many ceramics, are listed in Tables 2.16-2.18.
Beryllides are prepared by powder-metallurgy techniques. Typically,
the blended powders are heated to about 1260°C in inert magnesium oxide
or beryllium oxide containers, and the reacted powder is consolidated in
TABLE 2.15. BERYLLIDE TYPES
Formula
Structure
Metals
MBe
MBe2
M2Be17
MBe12
MBe
13
MBe 2 2
Cubic
Face-centered cubic
Hexagonal
Face-centered cubic
Cubic
Hexagonal
Rhombohedral
Body—centered
tetragonal
Face-centered cubic
Face-centered cubic
Ti(?), Co, Ni, Cu, Pd, Au
Ti, Cu, Nb, Ag, Ta
V, Cr, Mn, Fe, Zr, Mo, Hf, W, Re
Fe, Co(?), Pd
Au
Zr, Hf
Ti, Zr, Nb, Hf, Ta
Ti, V, Cr, Mn, Fe, Co, Nb, Mo,
Pd, Ag, Ta, W, Pt
Mg, Ca, Sc, Sr, Y, Zr, La, Ce, Pr,
Nd, Pm, Sin, Eu, Gd, Tb, Dy, Ho,
Er, Tm, Yb, Lu, Hf, Th, U, Np,
Pu, Am
Mo, Te, W, Re
Source: Stonehouse, 1971, Table 1, p. 73. Reprinted by permission
of the publisher.
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36
TABLE 2.16. HIGH-TEMPERATURE OXIDATION-RESISTANT BERYLLIDES
Beryllide
system
Nb-Be
Ta-Be
Mo-Be
Ti-Be
Zr-Be
Hf-Be
Compound
NbBej2
Nb2Be17
TaBe12
TaBejy
MoBe12
TiBe12
Ti2Be17
ZrBej 3
Zr2Bei7
HfBe13
Hf2Be17
Weight
percent
beryllitim
53.8
45.2
37.4
29.8
53.2
69.3
61.5
56.2
45.7
39.7
30.0
Melting
point
(°C)
1690
1700
1850
1990
-V1700
1600
1630
1900
1980
1600
<1750
X-ray
density
(g/cm3)
2.92
3.28
4.18
5.05
3.03
2.26
2.46
2.72
3.08
3.93
4.78
Structure
Body-centered tetragonal
Rhombohedral
Body-centered tetragonal
Rhombohedral
Body-centered tetragonal
Hexagonal
Rhombohedral
Face-centered cubic
Rhombohedral
Face-centered cubic
Rhombohedral
Source: Adapted from Stonehouse, 1971, Table 2, p. 74. Reprinted by permission of
the publisher.
TABLE 2.17. THERMAL CONDUCTIVITY OF SEVERAL BERYLLIDES
Compound
Nb2Be17
NbBe12
Ta2Be17
TaBe12
ZrBe13
Thermal conductivity [cal/sec(cm2) (°C/cm) ]
650°C
0.0748
0.0731
0.0698
0.0690
0.095A
870 °C
0.0764
0.0739
0.0723
0.0756
0.0909
1090 °C
0.0781
0.0752
0.0752
0.0805
0.0867
1320°C
0.0797
0.0764
0.0781
0.0867
0.0826
1430 °C
0.0805
0.0768
0.0752
0.0921
0.0805
Source: Adapted from Stonehouse, 1971, Table 8, p. 78.
Reprinted by permission of the publisher.
graphite molds by the vacuum hot-pressing technique (Stonehouse, 1971,
p. 79). Cold-pressing procedures and sintering techniques are also used.
Only minor amounts of beryllium are consumed as beryllides. The prin-
cipal applications are for high-temperature components for nuclear power
plants, high-performance turbine engines, and nuclear equipment components
requiring high strength and low density in the 1200°C to 1400°C temperature
range.
-------
37
TABLE 2. 18. ROOM-TEMPERATURE HARDNESS
OF SELECTED BERYLLIDES
Compound Vickers hardness, 2.5-kg load
1000
500
1120
720
Zr2Be17 1130
ZrBe13 1000
MoBei2 950
Source: Stonehouse, 1971, Table 3, p. 74.
Reprinted by permission of the publisher.
Several beryllium-rich beryllides - niobium beryllide (NbBe12), tan-
talum beryllide (TaBe12), titanium beryllide (TiBe12), and vanadium beryl-
lide (VBe12) - have been examined for potential toxicity by intratracheal
injections in rats. Despite the relatively high beryllium content of these
compounds, none of them showed pulmonary tumor induction and, in general,
had little or no biologic activity (Stokinger, 1972, p. 20).
2.2.8 Beryllium Nitrate
Beryllium nitrate, Be(N03)2-3H20, is a white to slightly yellow deli-
quescent crystalline compound. It has a molecular weight of 187.07, den-
sity of 1.557, melting point of 60°C, and boiling point of 142 C; it is
very soluble in water and ethanol. The Chemical Abstracts identification
number of beryllium nitrate trihydrate is 7787555.
Beryllium nitrate trihydrate is prepared by crystallizing a solution
of beryllium hydroxide or carbonate that has been treated with a slight
excess of concentrated nitric acid. The dihydrates and monohydrates are
also formed, depending on the concentration of the acid used. The anhy-
drous form may be obtained by treating an ethyl acetate solution of beryl-
lium chloride with dinitrogen tetroxide but not by dehydration of one of
the hydrated species; the latter operation results in the thermal decom-
position of the nitrate, with evolution of nitrous fumes (Everest, 1964,
p. 28).
Beryllium nitrate exhibits the usual hydrolytic reactions of the
divalent beryllium ion (Section 2.2.1.2). The salt is noteworthy only
because it has been used to stiffen and harden mantles in gas and acety-
lene lamps (Stecher, 1968), but it constituted a potential health hazard,
and its use was discontinued in 1973 (Griggs, 1973; Lerza, 1974).
-------
38
2.2.9 Beryllium Minerals
There are some forty-odd recognized mineral forms of beryllium. The
most important of these are listed in Table 2.3 with pertinent physical
properties. These minerals usually occur in pegmatites, in granites, in
syenites, and occasionally in gneisses and mica schists. At present, only
beryl and bertrandite are mined commercially.
Beryl is by far the most abundant and economically significant min-
eral form; it occurs in pegmatites as crystals, which sometimes weigh as
much as 50 to 60 tons. The commercial mineral is nontransparent and has
a vitreous luster resembling that of quartz. The beryllium oxide content
varies from 10% to 14%. Commercial ores usually contain 17% to 19% alumina,
64% to 70% silica, 1% to 2% alkali metal oxides, and 1% to 2% iron and
other oxides (U.S. Department of the Interior, 1953, p. 1-8). Beryl ore
is rarely found in quantities sufficient to permit mining as a primary ore;
it is usually produced as a by-product of other mining operations. Most
of the beryl consumed in the United States in 1969 was imported from Brazil,
South Africa, Argentina, and Uganda. Numerous small-scale beryl mining
operations exist in the United States, but firm data on production rates
are not available. In 1973, the total output from these operations was
estimated to be less than 10% of the total beryl ore process in the United
States (U.S. Environmental Protection Agency, 1973a, p. 2-4).
During the late 1950s and early 1960s, several new nonberyl deposits
of beryllium minerals were discovered in North America, the most important
being a large body of beryllium-bearing volcanic ash located in the Topaz
district of Utah. Typical ores from this region contain 0.5% to 1.0% beryl-
lium oxide (National Research Council, 1971, p. 18). Commercial mining of
this deposit began in 1969 (Heindl, 1970, p. 490); in 1973, it was the only
large operating beryllium mine in the United States. The ore is mainly
hydrated bertrandite, which can be readily extracted in high yield by sim-
ple leaching with mineral acids (Section 2.2.1.3).
2.2.10 Other Beryllium Compounds
Beryllium combines with many acidic, neutral, and metallic reactants
to form other salts, coordination compounds, and alloys. Most of these
substances are rarely used, and only a few need to be noted here; they are
listed and characterized in Table 2.19. Other properties of these compounds
are reviewed in Everest (1964), Krejci and Scheel (1966), and Novoselova
and Batsanova (1968).
2.3 ANALYSIS FOR BERYLLIUM
A variety of methods are available for the determination of beryllium
in environmental and biologic samples. Several of these methods are suffi-
ciently sensitive to detect beryllium in the low parts per billion concen-
tration range (Tables 2.20-2.24). The method of choice for a particular
application depends on several factors. Sample load, equipment availabil-
ity, and cost are key considerations. Detection limits, sample matrix,
specificity, speed of analysis, and accuracy are also relevant. These and
other factors pertinent to the selection of an analytical method and to
the evaluation of reported analytical data are summarized in this section.
-------
TABLE 2.19. PROPERTIES OF SELECTED BERYLLIUM COMPOUNDS
Beryllium compound
Acetate
Acetate, basic
Carbide
Carbonate, basic
Di-rc-buty Ibery Ilium
Die thy Ibery Ilium
Dime thy Ibery Ilium
Dipropy Ibery Ilium
Hydride
Hydroxide
Nitrate
Nitride
Oxalate
Oxide
Phosphate
Sulfate
Sulfide
Formula
Be(C2H302)2
BeO(C2H302)6
Be2C
BeC03 + Be (OH) 2
Be(Cl4H9)2
Be(C2H5)2
Be(CH3)2
Be(C3H7)2
BeH2
Be(OH)2 (see text)
Be(N03)2-3H20
Be3N2
BeC2Oi4-3H20
BeO
Be3(P01+)2-3H20
BeS04
BeS
Molecular
weight
127.10
406.32
30.04
112.05
123.24
67.14
39.09
95.19
11.03
43.03 (see text)
187.07
55.05
151.08
25.01
271.03
105.07
41.08
Melting Boiling
point point
(°C) (°C)
300 da
284 331
>2100 d
170 (25 torr)
12 110 (15 torr)
Subl. 200
<-17 245
125 d
60 142
2200 d 350 d
-3H20, 220 ^3900
2530
-H20, 100
550-600 d
Solubility in
Water
Insoluble
d
d
Insoluble
d
d
d
d
Insoluble
Very soluble
d
Soluble
Insoluble
Soluble
Insoluble
d
Ethanol
Insoluble
Soluble
Insoluble
Very soluble
U)
a
Decomposes.
Source: Adapted
from Weast, 1977, pp. B94, C688. Reprinted by permission of the publisher.
-------
40
TABLE 2.20. METHODS FOR DETERMINING BERYLLIUM: ATOMIC ABSORPTION SPECTROSCOPY
Important application
Sample preparation
Methodology or technique
Limit of detection
Flame method
Flameless method
Precision (relative
standard deviation)
Flame method
Flameless method
Accuracy (relative error)
Flame method
Flameless method
Interfering substances
Selectivity
Comments
Air, natural and treated waters, biologic tissues, urine, ores
Some liquid and solid samples require no preparation if the flame-
less technique is used. In the flame method, liquid samples are
acidified, and, if necessary, beryllium is separated from inter-
fering contaminants by chelation and extraction into an organic
solvent. Organic samples are wet-ashed with nitric, hydro-
fluoric, and hydrochloric acids or muffled at 400°C. The ash is
dissolved in acid, purified by solvent extraction, dried, and
taken up in dilute hydrochloric acid. Ores and refractory solids
are solubilized by fusion, purified by extraction, and dissolved
in dilute hydrochloric acid.
In the flame variation of this method the prepared sample is con-
tinuously aspirated into a nitrous oxide—acetylene flame through
which 234.9-nm radiation from a hollow-cathode lamp is passed.
The flame atomizes the sample, and radiation from the lamp is
selectively absorbed by beryllium atoms in proportion to their
concentration in the vapor. A photodetector measures the degree
of absorption and registers the concentration of beryllium in the
sample.
0.01 to 0,002 ng/mla
0.01 pg/gr (animal tissues)
0.1 ng/ml (urine)
1 to 10 ng/ml" (petroleum)
0.4 to 0.06 ng/ge (air filter sample)
34%^ (5 ng Be/g, water)
8%° (5 ng Be/g, urine)
10%" (30 ng Be/g, petroleum)
7£? (1.5 vg Be/g, coal)
f
20%J (5 ng Be/g, water)
2%f (50 ng Be/g, water)
3% (1 yg/ml, bovine liver)
2%°e (5 ng Be/g, urine)
5% (4 ng Be/filter, air sample)
Aluminum and silicon interfere at concentrations of 500 ug/ml or
greater.. Numerous ions enhance or depress the beryllium 4000 yg/ml
or more.^
Total beryllium is measured.
Atomic absorption spectrometry is the method of choice for many
samples; however, the flame technique may lack sufficient sensi-
tivity for some environmental samples.
^urlbut, 1974i.
Sanders et al., 1974.
CHurlbut, 1974fc.
Robbins, Runnels, and Merryfield, 1975.
CHurlbut and Bokowski, 1974.
•^Lishka and McFarren, 1970.
"Owens and Gladney, 1975.
Lockwood and Limtiaco, 1975.
''Fleet, Liberty, and West, 1970.
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41
TABLE 2. 21. METHODS FOR DETERMINING BERYLLIUM: SPECTROPHOTOMETRY
Important application
Sample preparation
Methodology or technique
Limit of detection
Precision (relative standard
deviation)
Accuracy (relative error)
Interfering substances
Selectivity
Comments
Air, natural and treated waters, ores, dusts, biologic samples
Solids are dissolved. Interfering contaminants in liquid
samples are chemically separated or masked by complexing
agents such as ethylenediaminetetraacetic acid or sodium
cyanide.
The sample is treated with aluminon, zenia, or other complex-
ing agents to form a colored beryllium lake or compound. The
optical absorbance of the latter is measured with a spectro-
photometer at a specified wavelength and related to the
beryllium concentration in the sample by a previously deter-
mined calibration chart.
5 ng/ml (aluminon method; water sample)
500 ng Be/filter*1 (aluminon method; air filter sample)
7% (250 ng Be/ml; aluminon method, water sample)
8%C (5 g Be/filter; zenia method, air filter sample)
12% (250 ng Be/ml; aluminon method, water sample)
5-10%* (500 ng Be/filter; aluminon method, air filter sample)
1-3%C (3 yg Be/filter; zenia method, air filter sample)
Many metals interfere. In the aluminon method, moderate
amounts of aluminum, cobalt, copper, iron, manganese, nickel,
titanium, zinc, and zirconium can be effectively masked with
ethylenediaminetetraacetic acid.
The method is not specific for beryllium; many other metals
also form colored complexes that absorb radiation in varying
degrees.
This method was used extensively earlier but is now being
replaced by more rapid, sensitive, and convenient techniques.
American Public Health Association, 1971.
bCrawley, 1960.
Q
Riser, Donaldson, and Schwenzfeier, 1961.
2.3.1 Sampling and Sample Handling
Although some ores, alloys, and beryllides contain beryllium in rela-
tively high concentrations, most environmental samples contain only trace
levels of the element. In biological samples, such as lung or liver tis-
sue, the concentration of beryllium is frequently in the parts per billion
range (Spencer et al., 1972). Under such circumstances, sample handling
techniques become very important. Containers and other equipment should
be scrupulously cleaned in hot detergent solutions, soaked in 8 N nitric
acid for 2 hr, and rinsed in distilled water following each use to prevent
the formation of adsorptive surfaces that might lead to cross contamination
of subsequent samples (Coulson et al., 1973, p. B7.1). It is also impor-
tant to control the acidity of beryllium solutions that are to be stored
or processed to prevent the hydrolysis and subsequent adsorption of the
hydrated species on the container wall. At pH 6, up to 20% of the 7Be in
a carrier-free solution of 0.1 M sodium chloride buffered with 0.001 M
sodium acetate is adsorbed on the surface of a glass container; under
similar conditions, somewhat less than 5% is adsorbed by polyethylene con-
tainers (Figure 2.6). The adsorption of trace-level 7Be by both glass and
polyethylene is essentially eliminated by reducing the solution pH to 4.5
and 5, respectively (Fairhall, 1960, p. 8). Other authorities recommend
acidifying beryllium solutions to below pH 2 to minimize transfer losses
between containers (Keenan, 1966, p. 134).
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42
TABLE 2.22. METHODS FOR DETERMINING BERYLLIUM: FLUOROMETRY
Important application
Sample preparation
Methodology or technique
Limit of detection
Precision (relative standard
deviation)
Accuracy (relative error)
Interfering substances
Selectivity
Comments
Air, natural and treated waters, blood, biologic tissues,
bone, urine
Solids are fused or ashed and are dissolved in acid. Liquids
are purified by extraction or by precipitation of beryllium
hydroxide, or interfering contaminants are masked by a suit-
able complexing agent. The final solution is carefully
alkalized and treated with a fluorescing agent, such as morin,
immediately prior to analysis .
The prepared sample is excited with ultraviolet radiation,
and a selected wavelength of the emitted fluorescence is
measured with a fluorometer. The beryllium concentration
in the sample is related to the intensity of the emitted
fluorescence by use of calibrated standards. When morin is
used, the exciting and emitted wavelengths are usually 436
and 550 nm, respectively .
400 pg/11 ml"2 (synthetic sample)
4 ng/11 ml^ (air filter samples, routine analysis)
0.4%° (0.2 g Be/11 ml, synthetic sample)
2%a (100 ng Be/5 ml, air filter sample)
8Z° (60 ng/5 ml, air filter samples)
10%" (500 ng/10 ml, air filter samples)
Yttrium, scandium, lanthanum, lithium, thorium, and zirconium
produce fluorescence with morin and must be removed or masked
by appropriate complexing agent.
Current fluorometric methods are not specific for beryllium.
Sensitive, but sample preparation can be long and tedious.
Good technique required
Sill and Willis, 1959.
^Kupel et al., 1971.
CWelford and Harley, 1952.
1959.
Organic matter in beryllium samples must usually be destroyed before
any of the separating or estimating procedures are applied. This ashing
process is sometimes troublesome and is frequently a significant source of
error. Ashing can be done wet or dry; wet ashing is convenient for process-
ing large numbers of samples and probably reduces the risk of exchanging
beryllium between the sample and the glaze of the ashing container, but it
is limited to relatively small samples. Dry ashing is usually required for
large bone samples. Early investigators reported losses of beryllium up
to 90% when dry ashing samples in platinum at 500°C to 900°C, presumably
because of volatilization of beryllium chloride (Cholak and Hubbard, 1948;
Peterson, Welford, and Harley, 1950). However, subsequent work established
that the beryllium was converted to the insoluble oxide (Toribara and Chen,
1952; Toribara and Sherman, 1953) or pyrophosphate complex (Keenan and
Holtz, 1964; Sill and Willis, 1959), which could be quantitatively recovered
by hydrolyzing the insoluble salt in strong mineral acids. An acid hydrol-
ysis step should thus be an essential part of recovery procedures in which
dry ashing has been used.
Recently, the presence of a volatile beryllium compound was reported
in orchard leaves. Black and Sievers (1973) observed a beryllium loss
greater than 85% during wet and dry ashing of such samples in an open
beaker at temperatures below 200°C. The addition of a cover glass to the
-------
43
TABLE 2.23. METHODS FOR DETERMINING BERYLLIUM: SPECTROMETRY
Important application
Sample preparation
Metholodogy or technique
Limit of detection
Precision (relative standard
deviation)
Accuracy (relative error)
Interfering substances
Selectivity
Comments
Air, biological samples
Solids are dissolved. Refractory and highly insoluble com-
pounds must be fused. Organic solids are digested with acids.
Liquids are treated with hydrochloric acid, extracted with
acetylacetone, and subsequently concentrated to about 0.5 ml
of aqueous solution, which is adjusted to pH 1 to 2 with
ammonium hydroxide.
The prepared sample is placed on or in graphite electrodes,
which are excited by an ac, dc, or plasma arc or a spark. The
resulting radiation passes through a monochromator, and
emission lines characteristic of each excited element are
recorded on film or photographic plates. The concentration
of each element is determined by comparing the density of its
emitted lines with that of an internal standard .
1 ng Be/0.05 mla
3 ng Be/mlfc
20 ng Be/liter
5-20%a (1 to 100 ng Be/2 mg rabbit liver ash)
2-30%d (0.1 to 200 vg Be/ml, synthetic sample)
2Q%° (20 ng Be/liter urine)
5-16%a (D.5-3.1% Be ore)
10-20%e (50-500 ng Be per air filter)
20%d (1-25 pg Be per air filter)
High concentrations of iron interfere if the 234.83-nm
beryllium line is used.
Spectroscopic determinations are highly specific for beryllium.
Chemical preparation and determination of typical samples and
standards are very time-consuming.
Keenan and Holtz, 1964.
bCholak, 1959.
2Barnes et al., 1949.
Peterson, Welford, and Harley, 1950.
SWatts et al., 1959.
d
beaker did not appreciably reduce the amount of beryllium lost; however,
the use of a cold trap or condenser greatly improved the retention of beryl-
lium (Table 2.25). The existence of volatile beryllium compounds in NBS
orchard leaves has been challenged, however, by Florence et al. (1974),
who carefully repeated the work of Black and Sievers without observing
volatile beryllium compounds. Florence et al. (1974) obtained essentially
complete recoveries of spiked samples processed by dry ashing, open beaker
digestion with acids, and wet ashing in closed systems (Table 2.26). The
results obtained by Black and Sievers were attributed by Florence et al.
(1974) to interference with the gas chromatographic measuring technique by
undestroyed organic matter.
2.3.1.1 Beryllium in Air — Airborne beryllium can occur as particulates,
dust, fumes, and volatile organic compounds. Beryllium in air is most
commonly sampled by means of a high-volume pump that draws air to be ana-
lyzed through a filter for a specified sampling period. Low-ash cellulose
fiber, cellulose ester, or fiberglass papers are usually used as filters
for nonvolatile contaminants, but they must be supplemented with liquid-
or solid-filled scrubbers or cold traps if volatile forms of beryllium are
-------
44
TABLE 2.24. METHODS FOR DETERMINING BERYLLIUM: GAS CHROMATOGRAPHY
Important application Air, water, and biologic samples
Sample preparation Refractory solids are fused with sodium carbonate. Air samples
are wet-ashed and extracted into benzene as the trifluoro-
acetylacetonate complex. Biologic fluids and tissues are
wet-ashed or ground, if necessary, and extracted directly with
trifluoroacetone in benzene. Excess complexing agent in the
extract is removed by washing with aqueous sodium hydroxide .
Methodology or technique
Limit of detection
Precision (relative standard
deviation)
Accuracy (relative error)
Interfering substances
Selectivity
Comments
In a typical procedure, the benzene extract of beryllium tri-
fluoroacetylacetonate is injected into a borosilicate or
polytetrafluoroethylene chromatographic column packed with
gas-chrom Z and 5% SE 52, a methyl phenyl silicone gum. The
sample is eluted at 100°C with nitrogen gas into a calibrated
electron-capture detector. The concentration of beryllium
in the sample is determined from the area of the appropriate
peak in the sample chromatogram.
0.04 pga b
<40 pg/m3 air
0.4 pgCj
1 ng/ml
0.08 pg
7-10%e (20-1000 ng Be/ml, blood)
13%" (30 ng/g, meteorite)
7%f (3-15 yg/ml, dog blood, rat liver)
3%^ (24 ng Be/ml, synthetic air filter sample)
5%S (20-1000 ng Be/ml, blood)
3-6%" (1 ng-2.7 ug Be/ml, urine)
10-30%° (1-100 ng Be, urine, blood)
$%f (3-15 yg/ml, dog blood, rat liver)
4%& (9 ng Be/ml, synthetic air filter sample)
Iron(III), aluminum(III), ammonium, and phosphate can inter-
fere at levels normally occurring in blood, urine, and tissues.
Organic materials can Interfere in direct extractions.
Gas chromatography is highly specific for beryllium.
A rapid, ultrasensitive, reliable technique.
Eisentraut, Griest, and Sievers, 1971.
Ross and Sievers, 1972.
CNoweir and Cholak, 1969.
Foreman, Gough, and Walker, 1970.
STaylor and Arnold, 1971.
fFrame et al., 1974.
ORNL-DWG 77-4513
4O
0. 30
cr
t/J 20
o
<
. 10
GLASS
POLYETHYLENE '
^34 5 6 7 8 9
pH
Figure 2.6. Adsorption of beryllium on the walls of polyethylene
and glass vessels as a function of the pH of the solution. Source:
Fairhall, 1960, Figure 1, p. 8.
-------
45
TABLE 2.25. BERYLLIUM CONCENTRATION IN ORCHARD LEAVES AS
A FUNCTION OF ORGANIC DIGESTION PROCEDURE
Type of digestion , .u Beryllium (ppn,)
'v & (with relative standard deviation)
Wet digestion, HN03 and H2SOij
Open beaker 0.017 ± 0.003
Covered beaker 0.017 ± 0.002
Low-temperature asher (ash), 0.0075 ± 0.0036
oxygen plasma
Low-temperature asher (cold trap)*3 0.085
Wet digestion, HN03 and H2SOi,, 0.11 ± 0.01
with condenser
Average of two measurements.
Source: Black and Sievers, 1973, Table 1, p. 1774. Reprinted by
permission of the publisher.
TABLE 2.26. BERYLLIUM IN NBS ORCHARD LEAVES
Beryllium in orchard Recovery of spike
Ashing procedure leaves (ppm)a' (%)
Dry ashing
450°C 0.019. 0.019° 101
600°C 0.017"
800°C 0.023, 0.027
Siliceous residue 0.008
Open beaker, HN03 + I^SOi, 0.027, 0.024, 0.018, 0.020 94, 95
Siliceous residue 0.009, 0.009
Method blank . <0.002e
Refluxed with HN03 + H2SO^ f 0.019
for 1 hr; then fumed in open beaker
ft
Gorsuch apparatus, HN03 + H2SOi,
HN03 <0.002
0.020
Gorsuch apparatus with dry ice trap
HN03 <0.002, <0.0029
H2SOit 0.021, 0.022? 95
Trap <0.002, <0.0029
Results are for separate 5-g weighings and have been corrected for moisture
content of 5.9% (24 hr at 90°C).
Results do not include beryllium in siliceous residue.
CAsh, 3.6%.
Limit of detection.
f
0.5 yg Be spike added at start of analysis.
^These three results were obtained on a second sample of orchard leaves received
from NBS six months after the first sample.
Source: Florence et al., 1974, Table 1, p. 1876. Reprinted by permission of
the publisher.
-------
46
also present. The filter is then processed by wet or dry oxidation, and
the residue is treated as required by the particular analytical technique
used. Extensive processing of the filter may be required if the sample
contains many metals that interfere with the identification and measurement
of beryllium. A basic sampling train suitable for all forms of airborne
beryllium is shown in Figure 2.7; it is described in detail by Martin
(1971). Current methods of monitoring airborne trace-metal particulates
are discussed further by Hendrickson (1968), Johnson (1974), and Skogerboe
(1974).
ORNL-DWG 77-5564
ACID
TRAP
HEATED AREA ^FILTER HOLDER THERMOMETER/ CHECK
. VALVE
•-WOBE
VACUUM
LINE
IMPINGERS ICE BATH
BY-PASS VALVE
THERMOMETERS
DRV Ti*T METER
MAIN VALVE
Figure 2.7. Sampling train. Source: Coulson et al., 1978,
Figure 2-1, p. 2-2.
2.3.1.2 Beryllium in Water — Because of the strong tendency of beryllium
salts to form insoluble hydrolytic species in aqueous solutions at pH 7
(Section 2.2.1.2), neutral environmental waters rarely contain beryllium in
concentrations as great as 1 pg/liter (Kopp and Kroner, 1970). This level
of concentration is two to three orders of magnitude below the limits set
to avoid deleterious effects to marine organisms (1.5 mg/liter) or agricul-
tural soils (0.1 mg/liter) (National Academy of Sciences-National Academy
of Engineering, 1973, pp. 244, 341) and is well below the detection limit
of all but the most sensitive analytical techniques. Consequently, analy-
ses of beryllium in neutral environmental waters are made only infrequently,
and this sample category is relatively unimportant. However, the highly
acidic or basic waste streams from facilities manufacturing or using beryl-
lium products are capable of dissolving toxic quantities of the element
and may require monitoring to avoid loss of an expensive raw material and
to protect the public welfare. Such samples should be collected in boro-
silicate glass or plastic containers and acidified, if necessary to below
-------
47
pH 2 to avoid losses by adsorption on the container wall. Sediments or
particulate matter in aqueous samples should be removed by filtration and
analyzed separately. Care should be taken to ensure that samples are repre-
sentative of the source material. This requirement is frequently difficult
to achieve; it involves the number of locations sampled, the size of the
individual samples, and the manner in which the samples are collected.
Brown, Skougstad, and Fishman (1970) discuss this subject extensively.
When the purpose of testing is to establish average concentrations in a
stream, 24-hr composite samples should be taken. If the aim is to show
peak concentrations, batch samples should be taken at appropriate intervals.
Descriptions of appropriate sampling systems are given in American Public
Health Association, American Water Works Association, and Water Pollution
Control Federation (1971).
2.3.1.3 Beryllium in Inorganic Solids — This sample category consists
chiefly of collected atmospheric dusts and fumes and of ores. All samples
should be ground, if necessary, to pass a 200-mesh sieve and should be
mixed thoroughly before sampling for analysis. Atmospheric particulates
and electrostatic precipitator dusts can frequently be dissolved in hot
nitric acid. Refractory residues and beryllium-containing silicate min-
erals, such as beryl, the bertrandites, phenacite, and chrysoberyl, can
be solubilized by fusing with a sodium carbonate-sodium tetraborate mixture
at 900°C or by treatment with potassium fluoride, followed by fusion with
sodium pyrosulfate (Keenan, 1966, pp. 140-141). The latter method not only
dissolves the beryllium but eliminates the silica and fluorides as well.
High-fired beryllium oxide is best dissolved by fusing with potassium hydrox-
ide (Everest, 1964, p. 118). Minerals in which beryllium occurs as the
phosphate or borate can be decomposed by heating with acids (Novoselova
and Batsanova, 1968, p. 154).
2.3.1.4 Beryllium in Organic Media — This sample category includes soft
animal tissues, bone, urine, and vegetable matter. Body tissue samples
should be collected in chemically clean glass containers and preserved in
formalin, or the container should be packed in dry ice to prevent decompo-
sition of the sample before analysis. Soft tissues, up to 20 g, and bone
samples, up to 4 g, can usually be satisfactorily prepared for analysis
by the nitric acid wet-ashing procedure, in which the sample is repeatedly
heated just to dryness after being covered initially with 5 ml of concen-
trated nitric acid and subsequently with just enough acid to moisten the
residue. The resulting white or light-colored soluble residue is dried
briefly at 400°C and cooled prior to weighing and quantitative analysis.
Some samples of lung tissue may contain refractory forms of beryllium oxide
or silicate, which require a potassium fluoride-sodium pyrosulfate fusion
(Section 2.3.1.3) before becoming soluble. After small bone samples have
been wet ashed, calcium is removed from solution by adding 5 ml of concen-
trated sulfuric acid and filtering the resulting calcium sulfate. Larger
samples of soft tissue and the few samples not amenable to the previously
described nitric acid wet-ashing procedure can be satisfactorily digested
with mixtures of nitric, sulfuric, and perchloric acid (Sill and Willis,
1964). Although very effective, this perchloric acid ashing procedure is
potentially hazardous because of the possibility of sublimed perchloric
acid accumulating on, and subsequently reacting violently with, organic
materials from the fume hood in which the ashing procedure is performed.
-------
48
Accordingly, the perchloric acid ashing procedure should be used only in
specially fabricated organic-free Transite fume hoods (Keenan, 1966,
p. 138).
Large bone samples are not suitable for wet-ashing procedures. After
drying to constant weight at 105°C, such samples can be dry ashed by plac-
ing them in a cold muffle furnace, raising the temperature gradually to
500°C, and heating for several hours. The resulting ash is extracted with
hydrochloric acid to recover the beryllium.
Urine should be collected in glass-stoppered borosilicate bottles and
acidified by the addition of 5 ml of concentrated nitric acid for each
250 ml of urine to prevent the adsorption of beryllium on the container
wall. Some analysts also add 2 ml of a 37% formalin solution to the sample
container to preserve the specimen until processed (Keenan and Holtz, 1964).
Small samples of urine (about 100 ml) are prepared for analysis by adding
5 ml of concentrated nitric acid and repeating the nitric acid wet-ashing
procedure described above for soft tissues. After the ashing procedure
is completed, the walls of the beaker should be washed with three separate
5-ml portions of 6 N hydrochloric acid, evaporating just to dryness after
each addition. This treatment hydrolyzes any condensed phosphates to ortho-
phosphate and converts the residue to the chloride form. The resulting
salt is suitable for use in the usual quantitative analytical procedures.
Large samples of urine (1 liter or more) cannot be treated as described
above because the resulting high concentration of calcium interferes with
subsequent analytical procedures. In such samples the bulk of the calcium
is removed by a sulfate precipitation in strongly acid solution, and the
remaining calcium and other heavy metals are complexed by addition of 20 ml
of 10% disodium ethylenediaminetetraacetic acid solution. The beryllium in
the resulting solution is then amenable to extraction by acetylacetone or
other appropriate chelating agents (Keenan, 1966, p. 146).
Thorough precautions must be taken to avoid contamination of the
urine sample during contribution. This is best accomplished by obtain-
ing samples after workers have showered and changed clothes at the end
of the work shift or prior to changing into working clothes at the begin-
ning of the work shift.
2.3.2 Separation and Concentration Methods
Because many of the current analytical techniques lack specificity,
beryllium must often be separated from interfering elements prior to anal-
ysis. Furthermore, in many tissue and urine samples, the concentration
of beryllium is well below the detection limit'of particular analytical
techniques, and preanalysis concentration is required. Solvent extrac-
tion is probably the most useful method for separating and concentrating
beryllium; other techniques include ion exchange, electrolytic methods,
and precipitation. The chief characteristics of these methods are dis-
cussed in the following sections.
2.3.2.1 Solvent Extraction — Solvent extraction is a rapid and rela-
tively simple technique for separating and concentrating beryllium from
other elements. The technique has considerable selectivity and, unlike
-------
49
precipitation, can be used for very small quantities of material (Andelman,
1971, p. 38). In this method, a beryllium complexing agent in an immis-
cible organic solvent is equilibrated with an aqueous solution containing
beryllium and cationic impurities which have been complexed with ethyl-
enediaminetetraacetic acid. The solvents are then separated, and the
organic phase, in which the complexed beryllium species preferentially
concentrates, is used as required, either for further separation and con-
centration or directly in analysis. The smaller the volume of extracting
solvent, the greater will be the concentration factor. The distribution
coefficient for a solute that is nonionic and in the same molecular form
in the two solvents is essentially equal to the ratio of its solubilities
in the solvents. By judiciously choosing the complexing agent and the
organic solvent, essentially all of the beryllium and little of the unde-
sirable elements are extracted from the aqueous phase. Acetylacetone is
commonly used to complex beryllium, but many other complexing agents, such
as trifluoroacetylacetone, diethyldithiocarbamate, 8-hydroxyquinaldine, and
cyclopentanone-2-carboxyaniline, are also useful (Butler, 1969; Hurlbut,
1974a, p. 4). Benzene, chloroform, and carbon tetrachloride are often
used as organic solvents. The extractability of acetylacetonates of beryl-
lium and selected group IB, IIB, and IIA metals in benzene as a function
of the pH of the aqueous solution is shown in Figure 2.8. It can be seen
that beryllium is quantitatively extracted between pH 4 and 7, while mag-
nesium, calcium, strontium, barium, and zinc are not extracted at all. By
using chloroform and other organic solvents instead of benzene, beryllium
can also be separated from other metals (Novoselova and Batsanova, 1968,
p. 118). Ethylenediaminetetraacetic acid is an effective masking agent
for these extractions because it strongly complexes the impurities but
not beryllium (Keenan, 1966, p. 146).
100
50
Be
ORNL-DWG 77-4509A
—T~
T
6
pH
10
12
Figure 2.8. Extraction curves of beryllium, copper, magnesium,
zinc, calcium, strontium, and barium with a 0.1 M solution of acetyl-
acetone in benzene as a function of the pH of the aqueous solution.
Source: Novoselova and Batsanova, 1968, Figure 27, p. 118.
-------
50
2.3.2.2 Ion Exchange — Beryllium can be effectively separated from sub-
stances that interfere with its fluorometric or chemical determination by
an ion exchange technique. For example, under acid conditions, positively
charged ions may be absorbed on cation exchangers, which characteristically
retain the polyvalent alkaline earth elements when the absorbed beryllium
is displaced with an appropriate eluting agent. Conversely, if a suitable
chelating agent, such as ethylenediaminetetraacetic acid, is used, aluminum,
trivalent iron, and other heavy metals may be eluted from the ion exchange
resin while beryllium is retained. Similar separations can be made with
anion exchange resins under alkaline conditions. Typical resin forms, elut-
ing agents, and operating conditions for a variety of ion exchange systems
are tabulated in Table 2.27. Other ion exchange separations of beryllium
are discussed by Korkisch and Feik (1965), Merrill, Honda, and Arnold (1960),
Strelow and Weinert (1970), and Toribara and Sherman (1953).
2.3.2.3 Electrolytic Methods — Many interfering elements can be simply
and conveniently removed from beryllium solutions by electrolysis with a
mercury cathode; the contaminants dissolve in the mercury to form amalgams,
which can be analyzed for their constituent metals if required. The tech-
nique is useful for the removal of 26 elements, including iron, chromium,
nickel, cadmium, copper, zinc, molybdenum, and tin. Beryllium, aluminum,
manganese, phosphorus, vanadium, the alkaline earths, and the rare earths
remain in solution (Keenan, 1966, p. 145). The latter impurities can be
removed, if necessary, by means of an acetylacetone extraction (Section
2.3.2.1). Conditions for the electrolysis vary with sample type; 0.5 g
of iron can be separated in 30 to 40 min using 3 to 4 A of current at 4 to
6 V. Even faster deposition rates can be achieved with cathodic current
densities of 1 to 6 A/dm2. The deposition rate is also a function of the
acidity of the solution; higher current yields occur at higher pH values
(Novoselova and Batsanova, 1968, p. 151). Needless to say, beryllium-free
mercury must be used to avoid contamination of samples when trace-level
determinations of beryllium are made. Other applications of this tech-
nique are cited by Noweir and Cholak (1969), Toribara and Sherman (1953),
and Vinci (1953).
2.3.2.4 Precipitation — Macro quantities of beryllium can be separated
from small amounts of impurities by precipitation as the phosphate, hydrox-
ide, or organic complex. Good selectivities are achieved if the impurities
are first complexed with sodium ethylenediaminetetraacetate; otherwise, the
precipitates are likely to be contaminated by adsorbed impurities (Novoselova
and Batsanova, 1968, pp. 143, 145). It is not feasible, however, to sepa-
rate micro amounts of beryllium from large quantities of other elements by
precipitation of sparingly soluble compounds; instead, beryllium is copre-
cipitated with calcium, manganese, titanium, and iron phosphates and with
aluminum and iron hydroxides. Recovery of coprecipitated beryllium can be
quantitative in the microgram range, but losses become appreciable at lower
concentrations. For example, Toribara and Chen (1952) recovered only 70%
of the beryllium coprecipitated with calcium phosphate when the initial
beryllium content was 0.1 yg or less. Although precipitation is probably
the oldest and one of the easiest means of separating and concentrating
beryllium, it is not the procedure of choice and must be used cautiously.
Any procedure for separating trace quantities of one element from large
-------
51
TABLE 2.27. ION EXCHANGE METHODS FOR SEPARATING BERYLLIUM
Resin form
Eluting agent
Ions eluted
Ions retained
HR
HR
HR
HR
HR
NHt,R
NHi,R
NaR
NaR
NHi,R
R citrate
RC1
RC1
Ca. 1 M 1IC1
0.05 M Ca or Mg
0.4 // oxalic acid
Oxalic acid, pH 4.4-5
5 // HC1
0.55 M ammonium
lactate, pH 5
10% (NHi+)2C03,
pH 8.5-9.0
EDTA, pH 3.5-4.0
0.35 // acetate
Acetylacetone, pH 5
0.1 M oxalic acid,
0.15 M HC1
1 M ammonium
citrate, pH 8
Cation exchange
Be
Be
Al, Fe(III), U022+
Th, others
Al, Fe
Be
Be
Be
Al, Fe(III), Mn(II),
heavy metals,
others
Be
Be
0.02 M sulfosalicylic Be
acid, pH 3.5-4.5
Anion exchange
Be
Be
Various concentrations Be
of HC1
Al, Ba, Ca, Mg, Sr
Al
Be
13 M LiCl
Alkali metals, Mg
Other alkaline earths
Cu, Ni
Be, alkaline earths
Al, alkaline earths,
U, others
Al, alkaline earths,
U, others
Ca, Cu, U
Al
Other alkaline earths
Many transition elements
Be
Source: Adapted from Keenan, 1966, Table 5.3, p. 149. Reprinted by permission of
the publisher.
amounts of other substances is subject to losses or contamination by occlu-
sion, adsorption, and coprecipitation. It is therefore necessary for the
user to demonstrate the validity of the precipitation procedure under exper-
imental conditions applicable to the samples before it is used for analysis
of unknown samples (Keenan, 1966, p. 143). Additional aspects of the sepa-
ration and concentration of beryllium by precipitation techniques are dis-
cussed by Barnes et al. (1949), Klemperer and Martin (1950), and Toribara
and Chen (1952).
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52
2.3.3 Methods of Analysis
Beryllium in environmental samples can be determined by a variety of
analytical procedures; those currently important or showing promise of
future usefulness are described in this section. The performance and limi-
tations of each method are emphasized rather than minute details of opera-
tion. Summaries of the methods are given in Tables 2.20-2.24. It is worth
noting that variations in sensitivity, precision, and accuracy occur not
only among different methods but also among various models of equipment and
among different operators (Karasek, 1975); the tabulated data should there-
fore be considered representative rather than definitive. Performance data
cited by workers responsible for developing an analytical technique usually
are obtained under optimized conditions and may not accurately reflect all
of the sources of error associated with the collecting, processing, and
analysis of environmental samples; interlaboratory comparisons — when they
exist — offer more realistic appraisals of particular analytical techniques.
2.3.3.1 Atomic Absorption Spectroscopy — Beryllium in air, natural and
treated waters, biologic tissues, and urine can be rapidly determined by
flame and flameless atomic absorption spectroscopy. In the flame technique,
a previously prepared sample is continuously injected into a nitrous oxide-
acetylene flame through which 234.9-nm radiation from a hollow-cathode lamp
is passed. The flame atomizes the sample, and radiation from the lamp is
selectively absorbed by beryllium atoms in proportion to their concentra-
tion in the vapor. A photodetector measures the intensity of the 234.9-nm
radiation after its passage through the flame and compares it with the
intensity of the original line spectrum emitted by the lamp (Figure 2.9).
The output of the photodetector is usually calibrated to read directly in
concentration values (Environmental Instrumentation Group, 1973a). The
sensitivity (1% absorption) and detection limits (twice background) under
Lomp selection
mirror
Reference beam
r~—i
ORNL-DWG 77-4515
Digital readout
AR25
Figure 2.9. Schematic diagram for the Unicam SP 1900, a double-
beam spectrophotometer. Source: Environmental Instrumentation Group,
1973a, Figure 2, p. 4.
-------
53
normal operating conditions are only about 0.03 and 0.01 to 0.002 yg/ml,
respectively, but these levels can be improved through solvent extraction
and concentration prior to assay (Bokowski, 1968; Hurlbut, 19742)). Sili-
con and aluminum in concentrations of about 500 ug/ml and numerous other
metals at 4000 yg/ml or more interfere with the beryllium absorption signal.
Interference by aluminum is reduced by adding 8-hydroxyquinoline (Fleet,
Liberty, and West, 1970). In interlaboratory comparisons of the flame ver-
sion of the atomic absorption method, unknown samples containing aluminum,
barium, and beryllium were analyzed in ten different laboratories with good
accuracy and moderately good precision, depending on the concentration of
beryllium in the sample (Table 2.28).
TABLE 2.28. SUMMARY OF INTERLABORATORY COMPARISONS OF BERYLLIUM
BY FLAME ATOMIC ABSORPTION SPECTROSCOPY
Sample
1
2
3
Beryllium
concentration
(mg/liter)
0.005
0.050
0.100
No. of
results
10
11
11
No. of
outliers
1
2
2
Mean
0.006
0.051
0.103
Mean
error
+0.001
+0.001
+0.003
S.D.a R.E.
0.0017 20.0
0.020 2.0
0.036 3.0
R.S.D.
34.0
39.2
35.0
S.D. = standard deviation; R.E. = relative error; R.S.D. = relative standard
deviation.
Source: Adapted from Lishka and McFarren, 1970, Tables C-4, C-5, and C-6, pp. 40-42.
Reprinted by permission of the publisher.
The flameless atomic absorption procedure for determining beryllium
is generally much more sensitive than the flame method. In this technique
a discrete volume of sample is atomized with an electrically heated carbon
rod, cup, or furnace (Figure 2.10) rather than a flame. An absorbance peak
of relatively short duration results, but the efficiency of atomization
approaches 100%, as compared with 2% to 8% by the flame technique (Environ-
mental Instrumentation Group, 1973a). As a consequence, the detection
limit of beryllium by the flameless atomic absorption procedure is reduced
tenfold or more compared with that for the flame technique. In addition,
in many instances, samples can be analyzed in the flameless procedure with-
out prior preparation. For example, in urine samples containing beryllium
at a concentration of 5 ng/g, Hurlbut (1974Z?) determined the element di-
rectly with a sensitivity (1% absorption) of 0.2 ng/g, a detection limit
(twice background) of about 0.1 ng/g, a relative standard deviation of 8%,
and a relative error of 2%. The precision and accuracy at other sample
concentrations are shown in Table 2.29. The rapidity and convenience of
the flameless atomic absorption technique is indicated by the author's
reporting the possibility of analyzing up to 200 urine samples per day by
the method. Robbins, Runnels, and Merryfield (1975) determined beryllium
in petroleum and petroleum products at the 30 to 40 ng of beryllium per
gram level with a precision of 10% and good recoveries from spiked sam-
ples; the detection limit varied from 1 to 10 ng of beryllium per gram,
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54
ORNL-DWG 77-4516
GAS IN
REMOVABLE WINDOW
HZOIN
HgOOUT
GRAPHITE TUBE
METAL JACKET
Figure 2.10. Cross section of the HGA-2000 (Perkin-Elmer) graphite
oven. Source: Environmental Instrumentation Group, 1973a, Figure 4,
p. 5.
TABLE 2.29. RECOVERY OF BERYLLIUM FROM SPIKED URINE
AND SPIKED ASHED URINE BASED ON AQUEOUS STANDARDS
Sample
a
Beryllium concentration (yg/liter)
Actual
Recovered
Blank urine
Blank water
Urine
Ashed urine
0.0
0.0
10.0
5.0
2.0
5.0
0.1
0.0
10.9?J<
5.1^'
2.0^'
5.1*"
aAll solutions were 4% (V/V) in sulfuric acid and
about 3% (V/V) in nitric acid.
The standard deviation is about ±0.4 pg/liter
based on six determinations.
Aqueous 5.0-yg/liter standards have a standard
deviation of about ±1.0 oh the basis of eight separate
determinations.
Source: Hurlbut, 1974&, Table 1, p. 3.
-------
55
depending on the type of furnace used. The accuracy of the results de-
pended somewhat on the experience of the analyst. Owens and Gladney (1975)
applied the flameless technique to four standard reference materials from
the National Bureau of Standards. Excellent agreement was obtained for
samples of coal (1.5 ppm Be) and fly ash (12 ppm Be), which were processed
by wet ash digestion, but disparate results occurred when orchard leaves
were analyzed directly and by wet ash digestion (Table 2.30). Whether the
orchard leaves data reflect loss of volatile organoberyllium compounds
(Section 2.3.1), formation of nonvolatile beryllium carbide in the graph-
ite atomizer (Runnels, Merryfield, and Fisher, 1975), anomalies associated
with the use of a tantalum sample boat, or some unspecified perturbation
was not determined. The data again emphasize the necessity of verifying
the validity of an analytical technique before introducing it for routine
use. Finally, Hurlbut and Bokowski (1974) demonstrated the effectiveness
of flameless atomic absorption spectrometry by determining nanogram amounts
of beryllium in air filter samples. They analyzed as little as 4 ng of
beryllium per paper filter with a relative standard deviation of 8% and a
relative error of 5%. The detection of beryllium collected on glass fil-
ters was limited to about 0.1 yg of beryllium per filter because of an
interfering nonatomic peak.attributed to aluminum. However, aluminum inter-
ference is not a major factor when a double-beam spectrometer equipped with
a deuterium background corrector is used.
2.3.3.2 Spectrophotometry — This analytical technique involves the forma-
tion of a colored beryllium complex that absorbs radiation in the visible
portion of the electromagnetic spectrum. The amount of radiation absorbed
by the sample is measured with a spectrophotometer and related to the metal
concentration by means of a previously prepared calibration chart. Numer-
ous complexes have been used for determining beryllium; most are formed by
TABLE 2.30. BERYLLIUM CONTENT OF NBS STANDARD
REFERENCE MATERIALS
(All values in ppm plus or minus standard deviation)
Standard reference material This work Other work
Fly ash (1633) 12.0 ± 0.8a 12
Coal (1632) 1.5 ± O.la 1.5
Orchard leaves (1571) 0.036 ± 0.004^ 0.030 ± 0.004
0.067 ± 0.007^
Bovine liver (1577) 0.005 ± 0.003° ^
Wet ash digestion.
Direct insertion of solid (Ta boat).
Source: Owens and Gladney, 1975, Table 1, p. 77.
Reprinted by permission of the publisher.
-------
56
treating the beryllium cation with an organic chelating agent. A few of
these complexing agents and the absorption maxima of their beryllium com-
plexes are shown in Table 2.31. Unfortunately, none of these reagents are
specific for beryllium, and many cationic and anionic interferences exist,
which must be removed chemically or masked by the addition of sodium ethyl-
enediaminetetraacetate or a similar reagent. Accordingly, spectrophoto-
metric procedures for beryllium are sometimes lengthy and tedious.
TABLE 2.31. COMPLEXING AGENTS COMMONLY USED FOR THE
SPECTROPHOTOMETRIC DETERMINATION OF BERYLLIUM
Reagent Maximal absorption (nm)
Acetylacetone 295
Aurintricarboxylic acid (aluminon) 515
Chrome Azurol S 575
Eriochrome Cyanine R 512
Fast Sulfon Black F 630
8-Hydroxyquinaldine 380
p-Nitrophenylazoorcinol (Zenia) 525
2-Phenoxyquinizarin-3,4'-disulfonic acid 550
Quinizarin-2-sulfonic acid 575
Source: Adapted from Keenan, 1966, Table 5.6, pp. 156-157.
Reprinted by permission of the publisher.
In a typical determination of beryllium in natural or treated water
using the aluminon method, the sample solution is first treated with ethyl-
enediaminetetraacetic acid to prevent interference from moderate amounts of
aluminum, cobalt, copper, iron, manganese, nickel, titanium, zinc, and zir-
conium; then the beryllium complex is formed by adding a buffered solution
of aluminon. The colored complex is developed in darkness for 20 min, after
which its absorbancy at 515 nm is measured with a spectrophotometer using
5-cm cells. The detection limit of the method is about 5 ng of beryllium
per milliliter. The precision and accuracy depend on the type and concen-
tration of the sample. In a study involving 32 laboratories, the beryllium
in a synthetic unknown sample of distilled water containing 250 yg/liter
beryllium, 40 yg/liter of arsenic, 240 yg/liter of boron, 20 yg/liter of
selenium, and 6 yg/liter of vanadium was determined by the aluminon method
with a relative standard deviation of 7% and a relative error of 12% (Amer-
ican Public Health Association, American Water Works Association, and Water
-------
57
Pollution Control Federation, 1971, p. 68). This level of precision and
accuracy is adequate for many environmental samples such as dusts, ores,
surface waters, and air filters, but the spectrophotometric technique is
being used less frequently today than formerly; it is being replaced by
more convenient or sensitive methods such as atomic absorption spectrometry
or gas chromatography.
2.3.3.3 Fluorometry — The fluorometric method is based on the measurement
of fluorescence radiation emitted by a beryllium compound previously excited
by ultraviolet or visible light. The emitted radiation results from the
transition of the excited molecule from the first excited singlet state to
the ground state — the frequency of the emitted light is therefore charac-
teristic of the analyte. The intensity of the emission is proportional to
the concentration of the analyte as well as the intensity of the exciting
radiation; accordingly, fluorometry is inherently very sensitive. Under
favorable conditions it can be four orders of magnitude more sensitive than
molecular absorption spectrophotometry (Mancy, 1971, p. 70). A simplified
schematic diagram of a filter-type fluorometer is shown in Figure 2.11. In
a typical application of fluorometry to the determination of beryllium in
environmental or biologic media, samples are prepared as described in Sec-
tion 2.3.1, treated with morin (2*,4',3,5,7-pentahydroxyflavone), and irra-
diated with either 365- or 436-nm radiation from a mercury or xenon lamp.
The intensity of the emitted 550-nm fluorescence is measured with a photo-
detector tube and related to the concentration of the beryllium in the sam-
ple by a predetermined calibration chart (Kupel et al., 1971). The inten-
sity of the fluorescence varies with temperature, morin concentration, pH,
and time. Lithium, scandium, zinc, and calcium also produce fluorescence
with morin in alkaline solution, and they must be removed or chelated with
ethylenediaminetetraacetic acid or a similar complexing agent to avoid
interference (Sill and Willis, 1959). Fluorescing agents other than morin,
such as l-amino-4-hydroxyanthraquinone, 2,3-hydroxynaphthoic acid, and 8-
hydroxyquinaldine can also be used but are not as sensitive as morin (Mancy,
ORNL-OWG 77-4SI8A
^MEASURING
PHOTOCELLS
SLIDE-WIRE
Figure 2.11. A schematic diagram of a filter-type fluorometer. X,
ultraviolet light source; LI, collimating lens; FI, primary filter passing
only ultraviolet light of a selected wavelength; F2, secondary filter
passing only fluorescent light; R, reduction plate; M, front-surface
mirror; and G, galvanometer. Source: Adapted from Mancy, 1971, Figure
6, p. 71. Reprinted by permission of the publisher.
-------
58
1971, p. 74). With the latter, under idealized conditions, as little as
400 pg of beryllium in 11 ml of solution can be detected, and 200 ng of
beryllium in 11 ml of solution can be determined with a relative standard
deviation of 0.4% (Sill and Willis, 1959). For routine analyses, a ten-
fold higher detection limit and less precision appear more realistic (Kupel
et al., 1971), but even with relaxed standards the fluorometric method is
exceeded in sensitivity only by the gas chromatographic method of deter-
mining beryllium. Only limited data are available for the precision and
accuracy of the method under routine conditions. Welford and Harley (1952)
reported an average recovery of 92% in analyses of 200 spiked air filter
samples. Walkley (1959) recovered 110% of the beryllium in ten spiked sam-
ples on filter paper. This level of accuracy is adequate for most air,
water, bone, blood, and organic tissue samples (American Industrial Hygiene
Association, 1969).
Despite the attractive sensitivity and accuracy of fluorometric deter-
minations of beryllium and the relatively low cost of equipment, sample
preparation is sometimes lengthy, with many variables and potential inter-
ferences. As a consequence, more convenient techniques, such as atomic
absorption spectrometry and gas chromatography, are preferred in some ana-
lytical laboratories.
2.3.3.4 Emission Spectroscopy — In emission spectroscopy, prepared sam-
ples are thermally or electrically excited, the resulting radiation is
resolved with a monochromator, and emission lines characteristic of each
excited element in the sample are recorded on film or photographic plates.
The concentration of each element is determined by comparing the density
of its emitted line with that of an internal or external standard. Use
of an internal standard — an element added to the sample in known amount —
is preferable to use of a separate external standard, since the former
tends to minimize the influence of procedural variables. The sample can
be excited by various techniques. When an ac or dc arc is used, the sam-
ple is usually placed on an electrode, and light from the electric dis-
charge between the electrodes is focused on the monochromator. In the
cathode layer technique, the graphite cathode is coated with the sample
and only light from the vicinity of the cathode is monitored. This tech-
nique increases the sensitivity of the analysis, but critical focusing is
required. In the porous cup technique, the liquid sample is fed into a
spark discharge by percolation through the thin base of a hollow graphite
electrode. The various modes of sample excitation, emission lines, inter-
ferences, internal standards, and sensitivities characteristic of several
commonly used spectroscopic procedures, for determining beryllium are sum-
marized in Table 2.32. In general, the spectroscopic determination of
beryllium is very specific, and elaborate sample purification procedures
are not needed; only when a strong emission line from an impurity falls
very near the chosen beryllium line — for example, iron at 234.83 nm and
beryllium at 234.86 nm — is it necessary to separate an impurity before
satisfactory measurement of the density of the beryllium line can be made
(Tepper, 1972a, p. 254).
On the other hand, attainment of maximum sensitivity by the spectro-
scopic technique requires the concentration of beryllium into a very small
-------
59
ac
TABLE 2.32. SPECTROGRAPHIC METHODS OF DETERMINING BERYLLIUM
Current
dc
dc
dc
Internal
standard Interferences
Molybdenum
Thallium Iron
Aluminum Organics and
phosphates
Wavelengths
(nm) Sensitivity
Be:265.1, 313.1; Mo:313.3 0.5 ug/ml
Be:234.9; Tl:238.0 0.25 ug/ml
Be:234.9, 265.1; Al:236.7 0.05 yg/sample
Aluminum
Be:313.1; Al:257-5
Be:313.1; Al:308.2
Be:234.9; Al:308.2
0.05 vg/sample
dc
ac
dc
Aluminum
Aluminum
Barium, Alkali metals
thallium
Be:234.5; Al:232.2
Be:313.1; Al:305.9
Be:234.9; Tl:276.8
Be:234.9; Ba:251.9
0.004 pg/sample
0.002 yg/sample
Source: Adapted from
Reprinted by permission of
American Industrial Hygiene Association, 1969, Table 1.
the publisher.
volume; therefore, preanalysis processing to remove large quantities of
extraneous matter is commonly practiced. The relationship between spectro-
scopic sensitivity for beryllium and sample size varies with sample type
and is illustrated in Table 2.33. These data are based on a spectroscopic
sensitivity of 3 ng of beryllium per milliliter and the use of 1/5 ml of
solution on the electrode (Cholak, 1959). Sensitivities of this order are
typical of many spectroscopic determinations of beryllium. Keenan and
Holtz (1964) observed sensitivities of 2 to 5 ng of beryllium per aliquot
(0.05 ml) using a sustaining ac arc excitation technique. The precision
of spectroscopic analyses of beryllium at this level varies appreciably
and is frequently poor (Hurlbut, 1974a, p. 6), but Keenan and Holtz (1964)
analyzed four replicate sets of rabbit liver ash samples containing 1 to
100 ng of beryllium with a relative standard deviation of 20% or less over
a six-month period (Table 2.34). The accuracy of the spectroscopic method
is generally inferior to that of other methods (Table 2.35), but this
characteristic is not as decisive for many environmental samples as speci-
ficity and sensitivity (Cholak, 1959).
Until the 1960s, emission spectroscopy was the most satisfactory
procedure for detecting and determining beryllium in trace-level samples.
Recently, cheaper, more accurate and convenient methods, such as atomic
absorption spectrometry and gas chromatography, have been developed and
are gradually replacing the older technique. However, the spectroscopic
determination of beryllium may continue to be economically attractive in
instances where multielement analyses are required.
2.3.3.5 Gas Chromatography — Gas chromatography is an analytical process
in which components of a volatile sample are physically partitioned between
a stationary bed of large surface area and a gas that percolates through
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60
TABLE 2.33. RELATIONSHIP BETWEEN SPECTROSCOPIC SENSITIVITY
FOR BERYLLIUM AND SIZE OF SAMPLE
Material
Sensitivity
desired
Size of sample
Urine
Tissue (lung)
Air (in plant)
Air (outside)
Urine
Tissue (lung)
0.01 yg/liter
0.01 yg/100 g
0.01 yg/m3
0.001 yg/m3
0.06-0.03 ug/liter
0.30-1.50 yg/100 g
333 ml
33.3 g
333 liters (11.77 ft3)
3333 liters (117.7 ft3)
50 ml
1 8
Source: Cholak, 1959, Table 2, p. 125. Reprinted by per-
mission of the publisher.
TABLE 2.34. RECOVERY OF BERYLLIUM ADDED TO 2-mg
QUANTITIES OF RABBIT LIVER ASH
Beryllium
added
(yg)
0.001
0.002
0.005
0.010
0.050
0.100
Beryllium
recovered
(yg)
0.0012
0.0019
0.0051
0.0108
0.0478
0.1055
Standard deviation
from beryllium added
(vg)
0.00020
0.00026
0.00029
0.00112
0.00577
0.02181
Coefficient of
variation
(%)
20.0
13.0
5.8
11.2
11.5
21.8
of four determinations.. •
Source: Keenan and Holtz, 1964, Table III, p. 261.
Reprinted by permission of the publisher.
and along the stationary bed. Typically, the stationary bed is a finely
divided column packing that is covered with a suitable liquid or solid
sorbent. An inert gas such as helium, argon, or nitrogen is usually used
as the carrier of the volatile phase. When the sample is introduced into
the chromatographic column, the unadsorbed carrier gas moves the various
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61
TABLE 2.35. RECOVERY OF BERYLLIUM FROM SPIKED SAMPLES
Beryllium
added
(Pg)
0.05
0.63
0.05
0.15
0.50
1.5
0.063
0.63
6.3
0.10
1.0
0.1
0.63
1.0
10.0
12.6
30.0
0.63
12.5
Collecting
filter
Millipore
Millipore
Millipore
Millipore
Millipore
Millipore
Glass
Glass
Glass
Glass
Glass
Whatman 41
Whatman 41
Whatman 41
Whatman 41
Whatman 41
Whatman 41
Whatman 41
Whatman 41
Compound
Beryllium oxide
Beryllium oxide
Beryllium sulfate
Beryllium sulfate
Beryllium sulfate
Beryllium sulfate
Beryllium oxide
Beryllium oxide
Beryllium oxide
Beryllium sulfate
Beryllium sulfate
Beryllium sulfate
Beryllium sulfate
Beryllium sulfate
Beryllium sulfate
Beryllium sulfate
Beryllium sulfate
Beryllium oxide
Beryllium oxide
Beryllium
recovered by
tnorin method
(ug)
0.08
0.61
a
0.23
0.45
a
a
0.48
6.8
0.12
0.88
a
0.64
a
a
12.6
a
a
a
Beryllium found
by spectrographic
method (pg)
0.034
0.65
0.032
0.31
0.60
1.64
0.11
0.62
7.1
a
a
0.15
a
1.2
9.8
a
28.2
0.85
16.0
Identical samples not available for analysis.
Source: Tepper, Hardy, and Chamberlin, 1961, Table XI, p. 165.
mission of the publisher.
Reprinted by per-
constituents of the sample through the column at a rate determined by the
interaction of each constituent with the sorbent. Since each constituent
has a slightly different affinity for the sorbent, each fraction of the
sample usually emerges from a well-designed column completely resolved from
other components after the passage of a characteristic volume of carrier
gas. Under standardized operating conditions, each component can be iden-
tified by its characteristic elution time. The composition of the original
sample is determined by identifying and measuring each component. Various
kinds of detectors are available for quantifying the fractions; electron
capture, flame ionization, and thermal conductivity types are commonly used.
A schematic diagram of a typical system is shown in Figure 2.12.
Use of gas chromatography for the determination of beryllium requires
that the metal be converted to a volatile form, such as a halide, 0-diketone,
or fluorinated 3-diketone; the trifluoroacetylacetonate appears to be the
most popular derivative (Frame et al., 1974; Schwarberg, Moshier, and Walsh,
1964). In a typical gas chromatographic analysis of environmental air
samples, Ross and Sievers (1972) prepared and injected this beryllium com-
plex into a 2-m-long, 3-mm-ID borosilicate glass column packed with 2.8%
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62
ORNL-DWG 77-4512
COLUMN
OVEN
INJECTION
PORT
AMPLIFIER
RECORDER
Figure 2.12. Schematic diagram of a gas chromatograph.
Environmental Instrumentation Group, 1973Z?.
Source:
W-98 silicone on Diataport S. The detector was an electron-capture type
equipped with a tritium ionizing source.
A mixture of methane (10%) and argon (90%) was used as the carrier
gas; the column and detector were maintained at 110°C and 200°C, respec-
tively. Excellent sensitivity, precision, and accuracy were obtained.
Beryllium was determined at the 400 pg of beryllium per cubic meter level
with a relative standard deviation of 3% and a relative error of 4%. The
limit of detection under the observed conditions was less than 40 pg of
beryllium per cubic meter. Preparation and analysis of the air filter
samples required about 40 min. Other investigators applied the gas chro-
matographic technique to the determination of beryllium in biologic media.
Taylor and Arnold (1971) determined beryllium in human blood spiked with
20 to 1000 ng of beryllium per milliliter with a relative standard devia-
tion of 7% to 10% and an average relative error of 5%. The limit of detec-
tion was 0.08 pg of beryllium in 0.5 to 1.0 yl of injected sample. Less
precise results were obtained with liver and spleen tissues of rats, but
the homogeneity of these samples was not established. The time required
for sample preparation and analysis averaged 15 min. Foreman, Gough, and
Walker (1970) determined beryllium in human and rat urine by gas chroma-
tography. Spiked samples containing from 1 to 2.7 vg of beryllium per
milliliter were extracted directly or after wet combustion with average
recoveries of 97% and 94%, respectively. A variety of chromatographic
substrates were studied; the best separation was achieved with Gas-Chrom
Z coated with a methyl phenyl silicone gum. The detection limit for beryl-
lium under these conditions was 1 yg/ml.
The superior sensitivity, selectivity, speed, and convenience of the
gas chromatographic method make it very attractive for the determination
of beryllium in environmental and biologic media, especially at ultratrace
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63
levels. These factors and the relatively modest cost of the required equip-
ment suggest that this technique may soon become the method of choice for
such samples in most analytical laboratories.
Other aspects and applications of the gas chromatographic technique
are discussed by Eisentraut, Griest, and Sievers (1971), Kawaguchi,
Sakamoto, and Mizuike (1973), Krugers (1968), Noweir and Cholak (1969),
Pauschmann and Bayer (1974, pp. 143-165), Ross and Sievers (1968), and
Wolf et al. (1972).
2.3.3.6 Other Methods — Other techniques for determining beryllium have
been demonstrated by various researchers. Most of these methods appear
attractive under special circumstances but seem unlikely to find wide-
spread acceptance in environmental or biologic applications. Included
in this category are polarography (Bacon and Ferguson, 1972; Blasius,
Janzen, and Fallot-Burghardt, 1971; Fogg, Kumar, and Burns, 1971; Galova
and Pantony, 1971), alpha activation (Engelmann, 1971a, 1971&), proton
activation (Golicheff, Loeuillet, and Englemann, 1972), neutron activa-
tion (Golanski, 1969), gamma activation (Lutz, 1971), microemission
spectrography (Brokeshoulder et al., 1966; Robinson et al., 1968), enzyme
inhibition (Guilbault, Sadar, and Zimmer, 1969; Townshend and Vaughan,
1969), atomic fluorescence (Chakrabarti, 1975), and ion-specific electrodes
(Fleet and Rechnitz, 1970).
2.3.4 Comparison of Analytical Procedures
Prior to the 1960s, beryllium in environmental and biologic samples
was determined primarily by spectroscopic, fluorometric, and spectrophoto-
metric methods. Among these, emission spectroscopy was probably the most
satisfactory method for detecting and determining traces of beryllium
because of its specificity and freedom from interferences; nevertheless,
it was still time-consuming, imprecise, and required expensive equipment
(Hurlbut, 1974a, p. 6). Fluorometry, especially the morin method, was
the most sensitive technique, easily detecting submicrogram concentrations
of beryllium; however, it was subject to many variables and interferences,
and samples frequently required lengthy preanalysis processing as well as
a high level of operator competence for satisfactory results. The spec-
trophotometric methods — of which the aluminon technique was probably the
most popular — lacked specificity and sensitivity, suffered from many inter-
ferences, and were frequently very time-consuming. As a result of these
deficiencies, the older methods have been replaced in many laboratories
by newer, more rapid and convenient techniques, such as atomic absorption
spectrometry and gas chromatography.
With the development by Willis (1965) of the high-temperature nitrous
oxide—acetylene flame, atomic absorption spectrometry became a useful and
convenient, though not ultrasensitive, beryllium procedure, which is rapid
and reasonably free of interferences. When needed, greater sensitivity
can often be obtained by substituting an electrically heated graphite atom-
izer for the nitrous oxide—acetylene flame. In some instances, use of the
flameless atomic, absorption technique also eliminates the need for sample
preparation. Atomic absorption spectrometry is thus attractive for environ-
mental samples requiring only moderate sensitivity.
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64
Even greater sensitivity and specificity are available in the gas
chromatographic method. When beryllium is chelated with trifluoroacetyl-
acetone and an electron-capture detector is used, as little as 0.08 pg of
beryllium can be detected by this technique (Taylor and Arnold, 1971). In
addition, sample preparation and analysis are usually rapid, interferences
are few, and equipment costs are moderate; the technique is thus very attrac-
tive for determining beryllium in environmental and biologic media.
Other analytical methods such as polarography, enzyme inhibition, and
various types of activation techniques also appear attractive for specific
limited applications but seem unlikely to be used extensively in the analy-
sis of a variety of environmental and biologic samples.
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65
SECTION 2
REFERENCES
1. Aldridge, W. N., J. M. Barnes, and F. A. Denz. 1949. Experimental
Beryllium Poisoning. Br. J. Exp. Pathol. (Great Britain) 30:375-389.
2. American Industrial Hygiene Association. 1969. Beryllium. In:
AIHA Analytical Guides. American Industrial Hygiene Association,
Akron, Ohio.
3. American Public Health Association, American Water Works Association,
and Water Pollution Control Federation. 1971. Standard Methods for
the Examination of Water and Wastewater, 13th ed. American Public
Health Association, Washington, B.C. 874 pp.
4. Andelman, J. B. 1971. Concentration and Separation Techniques. In:
Instrumental Analysis for Water Pollution Control, K. H. Mancy, ed.
Ann Arbor Science Publishers Inc., Ann Arbor, Mich. pp. 33-60.
5. Back, K. C. 1970. Aerospace Toxicology: I. Propellant Toxicology.
Fed. Proc. Fed. Am. Soc. Exp. Biol. 29(6):2000-2005.
6. Bacon, J. R., and R. B. Ferguson. 1972. Gravimetric and Coulometric
Analysis of Beryllium Samples Using 2-Methyl-8-quinolinol. Anal.
Chem. 44(13):2149-2152.
7. Baes, C. F., Jr., and R. E. Mesmer. 1974. The Hydrolysis of Cations,
Report No. ORNL-NSF-EATC-3, Part 1, Oak Ridge National Laboratory,
Oak Ridge, Tenn. 134 pp.
8. Barnes, E. C., W. E. Piros, T. C. Bryson, and G. W. Wiener. 1949.
Spectrochemical Determination of Beryllium in Microquantities. Anal.
Chem. 21(10):1281-1283.
9. Basolo, F. 1956. Theories of Acids, Bases, Amphoteric Hydroxides
and Basic Salts as Applied to the Chemistry of Complex Compounds.
In: The Chemistry of the Coordination Compounds, J. C. Bailar, Jr.,
ed. Reinhold Publishing Corp., New York. 834 pp.
10. Berry, J. W., D. W. Osgood, and P. A. St. John. 1974. Chemical Vil-
lains. The C. V. Mosby Company, St. Louis, Mo. 189 pp.
11. Black, M. S., and R. E. Sievers. 1973. Environmental Analysis Prob-
lems Created by Unexpected Volatile Beryllium Compounds in Various
Samples. Anal. Chem. 45(9):1773-1775.
12. Blasius, E., K.-P. Janzen, and W. Fallot-Burghardt. 1971. Polaro-
graphische Bestimmung von beryllium mit o-(2-Hydroxy-5-methyl-
phenylazo)-benzoesa"ure [Polarographic Determination of Beryllium
with o-(2-Eydroxy-5-methyl-phenylazo)-benzoic acid]. Talanta (Great
Britain) 18:273-278.
-------
66
13. Bokowski, D. L. 1968. Rapid Determination of Beryllium by a Direct-
Reading Atomic Absorption Spectrophotometer. Am. Ind. Hyg. Assoc. J.
29:474-481.
14. Brokeshoulder, S. F., F. R. Robinson, A. A. Thomas, and J. Cholak.
1966. Limits of Detection of Beryllium in Tissues by Microemission
Spectrography. Am. Ind. Hyg. Assoc. J. 27:496-500.
15. Brown, E., M. W. Skougstad, and M. J. Fishman. 1970. Methods for
Collection and Analysis of Water Samples for Dissolved Minerals and
Gases. In: Techniques of Water-Resources Investigations of the
United States Geological Survey. United States Government Printing
Office, Washington, D.C. 160 pp.
16. Browning, E. 1969. Beryllium. In: Toxicity of Industrial Metals,
2nd ed. Butterworths, London, pp. 67-86.
17. Butler, F. E. 1969. Concentration of Beryllium from Biological Sam-
ples. Am. Ind. Hyg. Assoc. J. 30:559-563.
18. Cartledge, G. H. 1928. Studies on the Periodic System: II. The
Ionic Potential and Related Properties. J. Am. Chem. Soc. 50:2863-
2872.
19. Chakrabarti, C. L. 1975. Beryllium, Boron, Aluminum, Gallium,
Indium, and Thallium. In: Flame Emission and Atomic Absorption
Spectrometry, Vol. 3, Elements and Matrices, J. A. Dean and T. C.
Rains, eds. Marcel Dekker, Inc., New York. pp. 96-115.
20. Cheng, K. K. 1956. Experimental Studies on the Mechanism of the
Zonal Distribution of Beryllium Liver Necrosis. J. Pathol. Bacteriol.
(Great Britain) 71:265-276.
21. Cholak, J. 1959. The Analysis of Traces of Beryllium. AMA Arch.
Ind. Health 19:205-210.
22. Cholak, J., and D. M. Hubbard. 1948. Spectrographic Determination
of Beryllium in Biological Material and in Air. Anal. Chem. 20:73-76.
23. Clary, J. J., and H. E. Stokinger. 1973. The Mechanism of Delayed
Biologic Response Following Beryllium Exposure. J. Med. 15(3):255-259.
24. Clary, J. J., L. S. Bland, and H. E. Stokinger; 1975. The Effect of
Reproduction and Lactation on the Onset of Latent Chronic Beryllium
Disease. Toxicol. Appl. Pharmacol. 33:214-221.
25. Cochran, K. W., M. M. Zerwic, and K. P. DuBois. 1951. Studies on
the Mechanism of Acute Beryllium Poisoning. J. Pharmacol. Exp. Ther.
102:165-178.
26. Cotton, F. A., and G. Wilkinson. 1962. Advanced Inorganic Chemistry.
John Wiley and Sons, Inc., New York. 959 pp.
-------
67
27. Coulson, D. M., D. L. Haynes, M. R. Balazs, and M. P. Bolder. 1973.
Survey of Manual Methods of Asbestos, Beryllium, Lead, Cadmium, Sele-
nium, and Mercury in Stationary Source Emissions. Report No. EPA-
650/4-74-015, Environmental Protection Agency, Durham, N.C.
28. Crawley, R.H.A. 1960. Spectrophotometric Determination of Beryllium
in Air and Dust. Anal. Chim. Acta (Netherlands) 22:413-420.
29. Deodhar, S. D., B. Barna, and H. S. Van Ordstrand. 1973. A Study of
the Immunologic Aspects of Chronic Berylliosis. Chest 63(3):309-313.
30. DuBois, K. P., K. W. Cochran, and M. Mazur. 1949. Inhibition of
Phosphatases by Beryllium and Antagonism of the Inhibition by Manga-
nese. Science 110:420-422.
31. Durocher, N. L. 1969. Preliminary Air Pollution Survey of Beryllium
and Its Compounds: A Literature Review. National Air Pollution Con-
trol Administration Publication No. APTD 69-29. U.S. Department of
Health, Education, and Welfare, Raleigh, N.C. 79 pp.
32. Dutra, F. R., and E. J. Largent. 1950. Osteosarcoma Induced by
Beryllium Oxide. Am. J. Pathol. 26:197-209.
33. Eisentraut, K. J., D. J. Griest, and R. E. Sievers. 1971. Ultra-
trace Analysis for Beryllium in Terrestrial, Meteoritic, and Apollo
11 and 12 Lunar Samples Using Electron Capture Gas Chromatography.
Anal. Chem. 43(14):2003-2007.
34. Engelmann, C. 1971a. Contribution a 1'Etude de la Determination de
Be, B, C, N, 0 et F par Activation au Moyen de p, d, 3He et a: I.
Courbes d'Activation et Sensibilities de Detection (Contribution to
the Study of the Determination of Beryllium, Boron, Carbon, Nitrogen,
Oxygen, and Fluorine by Proton, Deuteron, Helium-3, and Alpha Activa-
tion: I. Activation Curves and Limits of Detection). J. Radioanal.
Chem. 7:89-101.
35. Engelmann, C. 197Lb. .Contribution a 1'Etude de la Determination de
Be, B, C, N, 0 et F par Activation au Moyen de p, d, 3He et a: II.
Importance Relative des Principales Interferences Nucleaires. Condi-
tions d'Irradiation Optimales (Contribution to the Study of the Deter-
mination of Beryllium, Boron, Carbon, Nitrogen, Oxygen, and Fluorine
by Proton, Deuteron, Helium-3, and Alpha Activation: II. Relative
Importance of Principal Nuclear Interferences. Optimum Irradiation
Conditions). J. Radioanal. Chem. 7:281-298.
36. Environmental Instrumentation Group. 1973a. Instrumentation for
Environmental Monitoring — Biomedical. Report LBL-1, Vol. 4. Law-
rence Berkeley Laboratory, Berkeley, Calif.
37. Environmental Instrumentation Group. 1973&. Instrumentation for
Environmental Monitoring —Water. Report LBL-1, Vol. 2, Lawrence
Berkeley Laboratory, Berkeley, Calif.
-------
68
38. Erway, N. D., and R. L. Seifert. 1951. Vapor Pressure of Beryl-
lium Oxide. J. Electrochem. Soc. 98:83-88.
39. Everest, D. A. 1964. The Chemistry of Beryllium. Elsevier Pub-
lishing Co., New York. 151 pp.
40. Fairhall, A. W. 1960. The Radiochemistry of Beryllium. National
Academy of Sciences-National Research Council Report No. 3013, Of-
fice of Technical Services, Department of Commerce, Washington, B.C.
58 pp.
41. Fishbein, L. 1973. Chromatography of Environmental Hazards, Vol.
II. Metals, Gaseous and Industrial Pollutants. Elsevier Scien-
tific Publishing Co., New York. 637 pp.
42. Fleet, B., K. V. Liberty, and T. S. West. 1970. A Study of Some
Matrix Effects in the Determination of Beryllium by Atomic-Absorption
Spectroscopy in the Nitrous Oxide—Acetylene Flame. Talanta 17(3):
203-210.
43. Fleet, B., and G. Rechnitz. 1970. Fast Flow Studies of Biological
Reactions with Ion-Selective Membrane Electrodes. Anal. Chem.
42(7):690-693.
44. Florence, T. M., Y. J. Farrar, L. S. Dale, and G. E. Batley. 1974.
Beryllium Content of NBS Standard Reference Orchard Leaves. Anal.
Chem. 46(12):1874-1876.
45. Fogg, A. G., J. L. Kumar, and D. T. Burns. 1971. Further Polar-
ographic Studies of Metal Complexes of Mordant Red 74: The Masking
of Interfering Metals in the Determination of Beryllium or Lead.
Analyst 96:403-406.
46. Foreman, J. K., T. A. Gough, and E. A. Walker. 1970. The Deter-
mination of Traces of Beryllium in Human and Rat Urine Samples by
Gas Chromatography. Analyst 95:797-804.
47. Frame, G. M., R. E. Ford, W. G. Scribner, and T. Ctvrtnicek. 1974.
Trace Determination of Beryllium Oxide in Biological Samples by
Electron-Capture Gas Chromatography. Anal. Chem. 46(4):534-539.
48. Fricke, V. R., and H. Schutzdeller. 1923. Untersuchungen iiber
Hydrate in Wassriger Losung: I. Das Berylliumidn (Investigation
of Hydrates in Aqueous Solution: I. Beryllium Ion). Z. Anorg.
Chem. 131:130-139.
49. Galova, M., and D. A. Pantony. 1971. Application of Dimethylform-
amide in the Determination of Aluminum and Beryllium. Anal. Lett.
4(7):413-423.
-------
69
50. Gilbert, R. A., and A. B. Garrett. 1956. The Equilibria of the
Metastable Crystalline Form of Beryllium Hydroxide. Be(OH)2 in
Hydrochloric Acid, Perchloric Acid and Sodium Hydroxide Solutions
at 25°. J. Am. Chem. Soc. 78:5501-5505.
51. Golanski, A. 1969. Contribution to 14 MeV Neutron Activation
Analysis Using Half-Lives Between 0.55 and 873 Milliseconds. J.
Radioanal. Chem. 3:161-173.
52. Golicheff, I., M. Loeuillet, and C. Englemann. 1972. Analytical
Application of the Direct Observation of Nuclear Reactions Induced
by Low-Energy Protons and Leading to the Emission of "y-Photons,
Which Are Measured. J. Radioanal. Chem. 12:233-250.
53. Grier, R. S., M. B. Hood, and M. B. Hoagland. 1949. Observations
on the Effects of Beryllium on Alkaline Phosphatase. J. Biol. Chem.
180:289-298.
54. Griggs, K. 1973. Toxic Metal Fumes from Mantle-Type Camp Lanterns.
Science 181:842-843.
55. Guilbault, G. G., M. H. Sadar, and M. Zimmer. 1969. Analytical
Applications of the Phosphatase Enzyme System. Determination of
Bismuth, Beryllium and Pesticides. Anal. Chim. Acta (Netherlands)
44:361-367.
56. Hanifin, J. M., W. L. Epstein, and M. J. Cline. 1970. In Vitro
Studies of Granulomatous Hypersensitivity to Beryllium. J. Invest.
Dermatol. 55(4):284-288.
57. Heindl, R. A. 1970. Beryllium. In: Mineral Facts and Problems.
U.S. Department of the Interior, Bureau of Mines Bulletin 650, U.S.
Government Printing Office, Washington, D.C. pp. 489-501.
58. Hendrickson, E. R. 1968. Air Sampling and Quantity Measurement.
In: Air Pollution, 2nd ed. Vol II, A. C. Stern, ed. Academic Press,
New York. 684 pp.
59. Hiser, R. A., H. M. Donaldson, and C. W. Schwenzfeier. 1961. A
Rapid Analytical Method for the Determination of Beryllium in Air
Samples. Am. Ind. Hyg. Assoc. J. 22:280-285.
60. Hurlbut, J. A. 1974a. The History, Uses, Occurrences, Analytical
Chemistry, and Biochemistry of Beryllium — A Review. Dow Chemical
Co. Report RFP-2152, National Technical Information Service, U.S.
Department of Commerce, Springfield, Va. 24 pp.
61. Hurlbut, J. A. 1974£>. The Direct Determination of Beryllium in
Urine by Flameless Atomic Absorption Spectrometry. Dow Chemical
Co. Report RFP-2151, National Technical Information Service, U.S.
Department o-f Commerce, Springfield, Va. 4 pp.
-------
70
62. Hurlbut, J. A., and D. L. Bokowski. 1974. Determination of Sub-
microgram Amounts of Beryllium in Air Filter Samples by Nonflame
Atomic Absorption Spectrometry. U.S. Atomic Energy Commission Re-
port No. RFP-2287, U.S. Department of Commerce, Springfield, Va.
10 pp.
63. International Agency for Research on Cancer. 1972. IARC Mono-
graphs on the Evaluation of Carcinogenic Risk, Vol. 1, Lyon, France.
184 pp.
64. Jacobson, W., and M. Webb. 1952. Two Types of Nucleoproteins dur-
ing Mitosis. Exp. Cell Res. 3:163-183.
65. Johnson, J. L. 1974. Characterization of Air-Borne Particulates.
Microchem. J. 19(2):168-178.
66. Kakihana, H., and L. G. Sillen. 1956. Studies on the Hydrolysis
of Metal Ions: XVI. The Hydn
Acta Chem. Scand. 10:985-1005.
of Metal Ions: XVI. The Hydrolysis of the Beryllium Ion, Be2"1".
67. Karasek, F. W. 1975. Detection Limits in Instrument Analysis.
Research/Development, July. pp. 20-24.
68. Kawaguchi, H., T. Sakamoto, and A. Mizuike. 1973. Emission Specto-
metric Detection of Metal Chelates Separated by Gas Chromatography.
Talanta 20(3):321-326.
69. Keenan, R. G. 1966. Analytic Determination of Beryllium. In:
Beryllium— Its Industrial Hygiene Aspects, H. E. Stokinger, ed.,
Academic Press, New York. 393 pp.
70. Keenan, R. G., and J. L. Holtz. 1964. Spectrographic Determina-
tion of Beryllium in Air, Biological Materials, and Ores Using the
Sustaining A.C. Arc. Am. Ind. Hyg. Assoc. J. 25:254-263.
71. Klemperer, F. W., and A. P. Martin. 1950. Determination of Traces
of Beryllium in Biological Material. Anal. Chem. 22 (6):828-831.
72. Rlemperer, F. W., A. P. Martin, and R. W. Liddy. 1952. The Fate of
Beryllium Compounds in the Rat. Arch. Biochem. Biophys. 41:148-152.
73. Klemperer, F. W., J. W. Miller, and C. J. Hill. 1949. The Inhi-
bition of Alkaline Phosphatase by Beryllium. J. Biol. Chem. 180:
281-288.
74. Kopp, J. F., and R. C. Kroner. 1970. Trace Elements in Waters of
the United States. U.S. Department of the Interior, Federal Water
Pollution Control Administration, Cincinnati, Ohio.
75. Korenman, M., F. S. Frum, and G. A. Tsygankova. 1956. The Solubil-
ity Product of Beryllium Hydroxide. J. Gen. Chem. USSR 26:1745-1747.
-------
71
76. Korkisch, J., and F. Feik. 1965. Anion Exchange Separation of
Beryllium. Anal. Chem. 37(6):757-759.
77. Kovalenko, P. N., and 0. I. Geiderovich. 1959. Determination of
the pH of Precipitation and Activity Product of Beryllium Hydroxide.
Russ. J. Inorg. Chem. 4 (9):895-898.
78. Krejci, L. E., and L. D. Scheel. 1966. The Chemistry of Beryllium.
In: Beryllium — Its Industrial Hygiene Aspects, H. E. Stokinger,
ed., Academic Press, New York. 394 pp.
79. Krivanek, N., and A. L. Reeves. 1972. The Effect of Chemical Forms
of Beryllium on the Production of the Immunologic Response. Ind.
Hyg. Assoc. J. 33(l):45-52.
80. Krugers, J. 1968. System Components. In: Instrumentation in Gas
Chromatography, J. Krugers, ed., Centrex Publishing Co., Eindhoven.
245 pp.
81. Kupel, R. E., M. M. Braverman, J. M. Bryant, A. Carotti, H. M.
Donaldson, L. Dubois, and E. C. Tabor. 1971. Tentative Method of
Analysis for Beryllium Content of Atmospheric Particulate Matter.
Health Lab. Sci. 8(2):101-106.
82. Latimer, W. M., and J. H. Hildebrand. 1951. Reference Book of
Inorganic Chemistry, 3rd ed. The Macmillan Company, New York.
625 pp.
83. Lerza, C., ed. 1974. Eco Notes. Environmental Action, April 27,
p. 15.
84. Lishka, R. J., and E. F. McFarren. 1970. Water Metals No. 6.
Analytical Reference Service Report Number 37. U.S. Department of
Health, Education, and Welfare, Public Health Service, Cincinnati,
Ohio. 62 pp.
85. Lockwood, T. H., and L. P. Limtiaco. 1975. Determination of Beryl-
lium, Cadmium, and Tellurium in Animal Tissues Using Electronically
Excited Oxygen and Atomic Absorption Spectrophotometry, Am. Ind.
Hyg. Assoc. J. 36(l):57-62.
86. Lutz, G. J. 1971. Photon Activation Analysis —A Review. Anal.
Chem. 43(1):93-103.
87. Mancy, K. H. 1971. Elements of Instrumental Analysis. In: Instru-
mental Analysis for Water Pollution Control, K. H. Mancy, ed. Ann
Arbor Science Publishers, Inc., Ann Arbor, Mich. 331 pp.
88. Martin, R. M. 1971. Construction Details of Isokinetic Source-
Sampling Equipment. Air Pollution Control Office Publication
No. APTD-0581, Environmental Protection Agency, Research Triangle
Park, N.C. 32 pp.
-------
72
89. Merrill, J. R., M. Honda, and J. R. Arnold. 1960. Methods for
Separation and Determination of Beryllium in Sediments and Natural
Waters. Anal. Chem. 32(11):1420-1426.
90. Mesmer, R. E. , and C. F. Baes, Jr. 1967. The Hydrolysis of Beryl-
lium(II) in 1 M NaCl. Inorg. Chem. 6:1951-1960.
91. Naeye, R. L. 1973. Immunologic Aspects of Chronic Berylliosis.
Chest 63(3):306.
92. National Academy of Sciences—National Academy of Engineering. 1973.
Water Quality Criteria 1972. Environmental Protection Agency Report
No. EPA-R3-73-003, U.S. Government Printing Office, Washington, B.C.
594 pp.
93. National Research Council. 1971. Report of the Ad Hoc Committee
on Beryllium. A Report of the National Materials Advisory Board.
Report NMAB 281, National Academy of Sciences-National Academy of
Engineering, Washington, D.C. 93 pp.
94. Novoselova, A. V., and L. R. Batsanova. 1968. Analytical Chemistry
of Beryllium. In: Analytical Chemistry of Elements. Academy of
Sciences of the USSR. Israel Program for Scientific Translations,
Jerusalem.
95. Noweir, M. H., and J. Cholak. 1969. Gas Chromatographic Determina-
tion of Beryllium in Biological Materials and in Air. Environ. Sci.
Technol. 3(10):927-930.
96. Owens, J. W., and E. S. Gladney. 1975. Determination of Beryllium
in Environmental Materials by Flameless Atomic Absorption Spectro-
scopy. At. Absorpt. Newsl. 14(4):76-77.
97. Pauschmann, H., and E. Bayer. 1974. Gas Chromatography. In: Metho-
dicum Chimicum, Vol. I/A, Analytical Methods, F. Korte, ed. Academic
Press, New York. p. 143.
98. Peterson, G. E., G. A. Welford, and J. H. Harley. 1950. Spectro-
graphic Microdetermination of Beryllium in Air Dust Samples. Anal.
Chem. 22(9):1197-1200.
99. Reeves, A. L., and A. J. Vorwald. 1961. The Humoral Transport of
Beryllium. J. Occup. Med. 3:567-571.
100. Ricksecker, R. E. 1965. Copper Alloys. In: Kirk-Othmer Encyclo-
pedia of Chemical Technology, 2nd ed, Vol. 6, A. Standen, ed. John
Wiley, New York. p. 181-265.
101. Robbins, W. K., J. H. Runnels, and R. Merryfield. 1975. Analysis
of Petroleum for Trace Metals: Determination of Trace Quantities of
Beryllium in Petroleum and Petroleum Products by Heated Vaporization
Atomic Absorption. Anal. Chem. 47(13):2095-2101.
-------
73
102. Robinson, F. R. 1973. Toxicity of Beryllium and Other Elements in
Missle Propellants. Clin. Toxicol. 6(3):497-502.
103. Robinson, F. R., S. F. Brokeshoulder, A. A. Thomas, and J. Cholak.
1968. Microemission Spectrochemical Analysis of Human Lungs for
Beryllium. Am. J. Clin. Pathol. 49(6):821-825.
104. Ross, W. D., and R. E. Sievers. 1968. Rapid Ultra-Trace Determi-
nation of Beryllium by Gas Chromatography. Talanta 15:87-94.
105. Ross, W. D., and R. E. Sievers. 1972. Environmental Air Analysis
for Ultratrace Concentrations of Beryllium by Gas Chromatography.
Environ. Sci. Technol. 6(2):155-158.
106. Runnels, J. H., R. Merryfield, and H. B. Fisher. 1975. Analysis
of Petroleum for Trace Metals — a Method of Improving Detection
Limits for Some Elements with the Graphite Furnace Atomizer. Anal.
Chem. 47:1258-1263.
107. Sanders, C. L., W. C. Cannon, G. J. Powers, and R. R. Adee. 1974.
Toxicology of Inhaled Low-Fired and High-Fired Beryllium Oxides in
the Rat and Hamster. U.S. Atomic Energy Commission Report Number
BNWL-1818, National Technical Information Service, U.S. Department
of Commerce, Springfield, Va. 24 pp.
108. Schepers, G.W.H. 1962. The Mineral Content of the Lung in Chronic
Berylliosis. Dis. Chest 42 (6):600-607.
109. Schmidt, J. M. 1926. Analyse thermique des systemes binaires
formes par le chlorure de glucinium anhydre avec divers chlorures
metalliques (Thermal Analysis of Binary Systems Formed by Anhydrous
Beryllium Chloride with Different Metal Chlorides). Soc. Chim.
France Bull. 39(4):1686-1703.
110. Schwarberg, J. E., R. W. Moshier, and J. H. Walsh. 1964. Feasi-
bility of Gas-Liquid Chromatography for Quantitative Determination
of Aluminum(III), Gallium(III), Indium(III), and Beryllium(II)
Trifluoracetylacetonates. Talanta 11:1213-1224.
111. Schwenzfeier, C. W., Jr. 1964. Beryllium and Beryllium Alloys.
In: Kirk-Othmer Encyclopedia of Chemical Technology, 2nd ed.
Vol. 3, A. Standen, ed. John Wiley and Sons, Inc., New York.
112. Sidgwick, N. V. 1950. The Chemical Elements and Their Compounds,
Vol. I. Clarendon Press, Oxford. 853 pp.
113. Sill, C. W., and C. P. Willis. 1959. Fluorometric Determination
of Submicrogram Quantities of Beryllium. Anal. Chem. 31:598-608.
114. Sill, C. W., and C. P. Willis. 1964. Precipitation of Submicro-
gram Quantities of Thorium by Barium Sulfate and Application to
Fluorometric Determination of Thorium in Mineralogical and Biolog-
ical Samples. Anal. Chem. 36:622-630.
-------
74
115. Skogerboe, R. L. 1974. Monitoring Trace Metal Particulates: An
Evaluation of the Sampling and Analysis Problems. In: Instrumenta-
tion for Monitoring Air Quality, ASTM STP 555, American Society for
Testing and Materials, pp. 125-136.
116. Spandau, H., and G. Spandau. 1943. Uber die Diffusions- und
Dialysekoeffizienten der positiv geladen Elementarionen. Ein
Beitrag zur Bestimmung der Hydratation der Elementarionen (On the
Diffusion and Dialysis Coefficient of Positively Charged Ions. A
Contribution to the Determination of the Hydrated State of Simple
Ions). Z. Phys. Chem. 192:211-228.
117. Spencer, H. C., J. C. Jones, S. E. Sadek, K. B. Dodson, and A. H.
Morgan. 1965. Toxicological Studies on Beryllium Oxides. Toxicol.
Appl. Pharmacol. 7:498.
118. Spencer, H. C., S. B. McCollister, R. J. Kociba, and C. G. Humiston.
1972. Toxicological Studies on a Beryllium Containing Exhaust
Product. In: Proceedings of the 3rd Annual Conference on Environ-
mental Toxicology, October 25-27, 1972. AMRL-TR-72-130, Aerospace
Medical Research Laboratory, Wright-Patterson Air Force Base, Ohio.
pp. 303-316.
119. Stecher, P. G. 1968. The Merck Index. 8th ed. Merck & Co., Inc.
Rahway, N.J.
120. Sterner, J. H. , and M. Eisenbud. 1951. Epidemiology of Beryllium
Intoxication. Arch. Ind. Hyg. Occup. Med. 4:123-151.
121. Stokinger, H. E. 1972. Experimental Toxicology. In: The Toxi-
cology of Beryllium, I. R. Tabershaw, ed. Publication No. 2173,
Public Health Service, U.S. Government Printing Office, Washington,
D.C. pp. 17-32.
122. Stonehouse, A. J. 1971. Beryllides. In: Kirk-Othmer Encyclopedia
of Chemical Technology, 2nd ed, Supplement, A. Standen, ed. John
Wiley and Sons, Inc., New York.
123. Strelow, F.W.E., and C.H.S.W. Weinert. 1970. Comparative Distri-
bution Coefficients and Cation-Exchange Behavior of the Alkaline
Earth Elements with Various Complexing Agents. Talanta 17:1-12.
124. Taylor, M. L., and E. L. Arnold. 1971. Ultratrace Determination
of Metals in Biological Specimens: Quantitative Determination of
Beryllium by Gas Chromatography. Anal. Chem. 43(10):1328-1331.
125. Tepper, L. B. 1972a. Beryllium. In: Critical Reviews in Toxi-
cology, Vol. I, Issue 3. CRC Press, Cleveland, Ohio. pp. 235-259.
126. Tepper, L. B. 19723. Beryllium. In: Metallic Contaminants and
Human Health, D.H.K. Lee, ed. Academic Press, New York. pp. 127-137.
-------
75
127. Tepper, L. B., H. L. Hardy, and R. I. Chamberlin. 1961. Toxicity
of Beryllium Compounds. Elsevier Publishing Co., New York.
190 pp.
128. Toribara, T. Y., and P. S. Chen, Jr. 1952. Separation of Beryllium
from Biological Material. Anal. Chem. 24:539-542.
129. Toribara, T. Y., and R. E. Sherman. 1953. Analytical Chemistry of
Micro Quantities of Beryllium. Anal. Chem. 25:1594-1597.
130. Townshend, A., and A. Vaughan. 1969. Applications of Enzyme-
Catalyzed Reactions in Trace Analysis — IV: Determination of Beryl-
lium and Zinc by Their Inhibition of Calf-Intestinal Alkaline
Phosphatase. Talanta 16:929-937.
131. U.S. Department of the Interior, Bureau of Mines. 1953. Materials
Survey, Beryllium. U.S. Government Printing Office, Washington, D.C.
p. 1-15.
132. U.S. Department of the Interior, Bureau of Mines. 1971. Informa-
tion Circular 8502, U.S. Government Printing Office, Washington,
D.C. p. 2.
133. U.S. Environmental Protection Agency. 1973a. Control Techniques
for Beryllium Air Pollutants. Report No. AP-116, U.S. Government
Printing Office, Washington, D.C. 54 pp.
134. U.S. Environmental Protection Agency.- 1973&. National Emission
Standards for Hazardous Air Pollutants. Asbestos, Beryllium, and
Mercury. Fed. Regist. 38(66):8820-8850.
135. U.S. Environmental Protection Agency. 1973c. Comprehensive Study
of Specified Air Pollution Sources to Assess the Economic Impact
of Air Quality Standards Asbestos, Beryllium, Mercury. Vol. II.
Research Triangle Institute.
136. Vacher, J. 1972. Immunological Responses of Guinea-Pigs to Beryl-
lium Salts. J. Med. Microbiol. 5:91-108.
137. Vacher, J., and H. B. Stoner. 1968a. The Transport of Beryllium
in Rat Blood. Biochem. Pharmacol. 17:93-107.
138. Vacher, J., and H. B. Stoner. 1968£>. The Removal of Injected Beryl-
lium from the Blood of the Rat. Br. J. Exp. Pathol. 49(3):315-323.
139. Vacher, J., R. Deraedt, and J. Benzoni. 1973. Compared Effects of
Two Beryllium Salts (Soluble and Insoluble): Toxicity and Blockade
of the Reticuloendothelial System. Toxicol. Appl. Pharmacol.
24:497-506.
140. Vacher, J., R. Deraedt, and M. Flahaut. 1975. Possible Role of
Lysosomal Enzymes in Some Pharmacological Effects Produced by Beryl-
lium. Toxicol. Appl. Pharmacol. 33:205-213.
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76
141. Veerkamp. T. A., and G. Smits. 1953. Mode of Action of Beryllium
on Alkaline Phosphatase. Nature (London) 172:589-590.
142. Versar, Inc. 1975. Assessment of Industrial Hazardous Waste Prac-
tices. Inorganic Chemicals Industry. Final report for Environ-
mental Protection Agency, Office of Solid Waste Management Programs,
Washington, B.C. pp. 5-145 to 5-149 and A-ll to A-14.
143. Vinci, F. A. 1953. Analytical Chemistry of Beryllium. Anal. Chem.
25(11):1580-1585.
144. Vorwald, A. J., A. L. Reeves, and E.C.J. Urban. 1966. Experimental
Beryllium Toxicology. In: Beryllium — Its Industrial Hygiene
Aspects, H. E. Stokinger, ed. Academic Press, New York. 394 pp.
145. Walkley, J. 1959. A Study of the Morin Method for the Determination
of Beryllium in Air Samples. Am. Ind. Hyg. Assoc. J. 20:241-245.
146. Watts, S. R., F. X. Walsh, and V. M. Vought. 1959. Analytical
Experiences with Beryllium Determinations in a Comprehensive Air
Pollution Study. Am. Ind. Hyg. Assoc. J. 20:500-503.
147. Weast, R. C., ed. 1977. Handbook of Chemistry and Physics, 58th ed.
The Chemical Rubber Co., Cleveland, Ohio.
148. Welford, G., and J. Harley. 1952. Fluorimetric Determination of
Trace Amounts of Beryllium. Am. Ind. Hyg. Assoc. J. 13:232-234.
149. Willis, J. B. 1965. Nitrous Oxide—Acetylene Flame in Atomic Absorp-
tion Spectroscopy. Nature (London) 207:715-716.
150. Witschi, H. P., and W. N. Aldridge. 1967. Biochemical Changes in
Rat Liver after Acute Beryllium Poisoning. Biochem. Pharmacol.
16:263-278.
151. Witschi, H. P., and W. N. Aldridge. 1968. Uptake, Distribution and
Binding of Beryllium to Organelles of the Rat Liver Cell. Biochem.
J. 106:811-820.
152. Wolf, W. R., M. L. Taylor, B. M. Hughes, T. 0. Tiernan, and R. E.
Sievers. 1972. Determination of Chromium and Beryllium at the
Picogram Level by Gas Chromatography-Mass Spectrometry. Anal. Chem.
44(3):616-618.
-------
SECTION 3
BIOLOGICAL ASPECTS IN MICROORGANISMS
3.1 SUMMARY
Microorganisms absorb beryllium when exposed to soluble compounds;
however, the form of the absorbed element is not known. The addition of
beryllium at an initial pH of 11.4 promotes growth of magnesium-deficient
algae due to partial substitution of beryllium for magnesium in the orga-
nism's metabolism. The substitution appears to be pH-dependent, as beryl-
lium is toxic to microorganisms below pH 7 regardless of the magnesium
level.
Normally, beryllium inhibits the growth of microorganisms. Growth
may be inhibited by more than 50% in the presence of 2 x 10~6 M beryllium
solutions. The degree of beryllium toxicity depends on environmental con-
ditions, with toxicity increasing in a subootimal environment.
3.2 METABOLISM
In microorganisms, beryllium is absorbed into the cell as well as
adsorbed to the outer cell surface (Hoagland, 1952; Karlander and Krauss,
1972). Green algae absorb 1 to 44 ng of beryllium per milligram of dry
weight when grown in constant levels of soluble beryllium compounds
(Karlander and Krauss, 1972). The form of beryllium that is most likely
to be absorbed by algae has not been determined.
3.3 EFFECTS
3.3.1 Physiological Effects
Under high initial pH conditions, beryllium can serve as a growth
promoter in magnesium-deficient microorganisms (Figure 3.1). Beryllium
concentrations of 2 x 10"* to 3 x 10~A M increased growth nearly 60% in
magnesium-deficient Chlorella pyrenoidosa at an initial pH of 11.3 to 11.5
(Hoagland, 1952). Steinberg (1946) increased the yield of magnesium-
deficient Aspergillus niger by the addition of 5 mg of beryllium per liter
but found that as magnesium levels were increased to optimum, the beryllium-
induced response decreased. A decrease in pH or an excess of micronutri-
ents in the solution prevented the increased growth.
Although beryllium stimulates growth by substituting for magnesium
in the microorganisms' metabolism (Hoagland, 1952), the substitution is
not perfect because magnesium is an essential element and must be present
at a minimum concentration for the organism to thrive. The substitution
appears to increase growth only at high pH. At pH 7 or below, beryllium
is toxic to algae regardless of the magnesium levels of the organism. It
is not clear whether pH affects the site of action for beryllium or mag-
nesium, the state of the beryllium itself, the lability of bound magnesium,
or a combination of these possibilities. Hoagland (1952) has suggested
77
-------
78
ORNL-DWG77-4594A
20
15
o
o
10
0
I
O 1 X 10 4 M magnesium without beryllium
• 1 X 10~4 M magnesium and 2 X 10~4 M beryllium
A 2 X 10 M magnesium without beryllium
A 2 X 10~3 M magnesium and 2 X 10~4 M beryllium
8 10
INITIAL pH
12
Figure 3.1. The growth of algae (70 hr) as a function of the
initial pH of the nutrient solution (one of four similar experiments),
that at high pH the beryllate ion (Be02)2~ forms and is responsible for
growth promotion of magnesium-deficient algae, while at low pH a differ-
ent species of beryllium causes toxicity.
3.3.2 Toxic Effects
Under normal pH and magnesium conditions, beryllium inhibits the
growth of microorganisms. Beryllium chloride, fluoride, and sulfate in-
hibit the growth of the yeast Saccharomyces cerevisi,ae and of Esdherioh'ia
coli. (Loveless, Spoerl, and Weisman, 1954). Yeast cells were found to
undergo abnormal multiple budding after incubation (Manil and Straszewska,
1953). Beryllium concentrations of 2000 vg/ml reduced growth by over 50%.
MacCordick, Hornsperger, and Wurtz (1975) and MacCordick, Wurtz, and
Hornsperger (1975) found the beryllium concentrations of 2 x 10"6 M or
more reduced growth of Pseudomonas fluovesaens.
The toxicity of beryllium depends on the environmental conditions as
well as the concentration of the metal in solution (Karlander and Krauss,
1972). Under optimal conditions, the growth of ChloYella -0(xnniel1-i was
not affected by a concentration of 100 mg of beryllium per liter. Under
suboptimal conditions (limited C02, limited light, variable temperature),
however, the same beryllium concentration completely halted growth.
-------
SECTION 3
REFERENCES
1. Hoagland, M. B. 1952. Beryllium and Growth: II. The Effect of
Beryllium on Plant Growth. Arch. Biochem. Biophys. 35:249-258.
2. Karlander, E. P., and R. W. Krauss. 1972. Absorption and Toxicity
of Beryllium and Lithium in ChtoTPella, vanniel'iT, Shihira and Krauss.
Chesapeake Sci. 13:245-253.
3. Loveless, L. E., E. Spoerl, and T. H. Weisman. 1954. A Survey of
Effects of Chemicals on Division and Growth of Yeast and Esohenahia
GoH. J. Bacteriol. 68:637-644.
4. MacCordick, J., J.-M. Hornsperger, and B. Wurtz. 1975. Action d'un
Complexe de Beryllium sur la Croissance de Pseudomonas fluoYescens
(Types R et S): I. Influence sur le Temps de Latence [Action of a
Beryllium Complex on the Growth of Pseudomonas fluorescens (Types R
and S): I. Influence on Incubation Time]. C. R. Seances Soc. Biol.
(France) 169:417-420.
5. MacCordick, J. B., B. Wurtz, and J.-M. Hornsperger. 1975. Action
d'un Complexe de Beryllium sur la Croissance de Pseudomonas fluovesaens
(Types R et S): II. Competition avec le Magnesium [Action of a Beryl-
lium Complex on the Growth of Pseudomonas fluoresoens (Types R and
S): II. Competition with Magnesium]. £. R. Seances Sec. Biol.
(France) 169:421-425.
6. Manil, P., and Z. Straszewska. 1953. Action de Sulfate de Beryllium
sur la Levure (Action of Beryllium Sulfate on Yeast). C. R. Seances
Soc. Biol. (France) 147:525.
7. Steinberg, R. A. 1946. Specificity of Potassium and Magnesium for
Growth of Aspergillus niger. Am. J. Bot. 33:210-214.
-------
SECTION 4
BIOLOGICAL ASPECTS IN PLANTS
4.1 SUMMARY
Few data exist on the metabolism or effects of beryllium in higher
plants. Soluble beryllium is absorbed by roots from solution cultures
and soils. The amount absorbed increases with increasing acidity of the
source solution. Only a small amount of beryllium is translocated from
roots to shoots. Beryllium concentrations in crop plants and noncrop
plants are usually small (about 0.1 ppm dry weight in plants containing
beryllium; however, many do not contain measurable amounts). There are
no data on the bioelimination of beryllium from living plant tissues.
Although low beryllium concentrations may enhance growth, most re-
sults show beryllium to be toxic. The symptoms of beryllium toxicity are
not specific. Root damage is a common observation. Leaves may become a
darker green or become mottled (citrus). In the culture solution, the
concentration of beryllium which induces this toxicity is about 1 ppm;
typically, the corresponding concentration of beryllium in the root is a
few hundred parts per million.
At pH values greater than 9, beryllium can increase growth when mag-
nesium levels are low; however, at lower pH values, increased growth may
not occur. Plant phosphatases are inhibited in vitro by beryllium, but
data on the significance of this experiment in vivo are lacking.
4.2 METABOLISM
4.2.1 Uptake
Few data exist addressing the problem of beryllium uptake in higher
plants. It is apparent, however, that uptake of beryllium from both soil
and nutrient solutions does occur (Romney and Childress, 1965; Williams
and Le Riche, 1968). Nikonova (1971) considers pine, birch, aspen, and
willow the best accumulator plants for soil beryllium. In these plants,
beryllium content may rise as high as 3 ppm; they are recommended as indi-
cators of exploitable ore deposits underneath. Increasing the beryllium
concentration in nutrient solution culture experiments increases the beryl-
lium content of plant material (Table 4.1). Similar increases are found
in bush beans growing in nutrient culture with beryllium (Table 4.2)
(Romney, Childress, and Alexander, 1962) and in "Lea mays grown in soil
with beryllium nitrate (Oustrim et al., 1967). Hoist, Schmid, and Yopp
(1975) suggest that uptake by excised barley roots was passive because
the Qio for uptake was only 1.2.
The form of beryllium in soil affects the extent of uptake in plants.
High concentrations of insoluble BeC03 and BeO did not influence bean
growth, whereas Be(N03)2 and BeSO*, at 10 ppm did inhibit growth (Romney
and Childress, 1965). Presumably, inhibition reflects increased uptake
80
-------
81
TABLE 4.1 BERYLLIUM CONCENTRATION IN PLANT MATERIAL EXPOSED TO
BERYLLIUM IN NUTRIENT SOLUTIONS
Beryllium concentration Beryllium concentration
Plant tissue in nutrient solution in dry plant tissue
(ppm) (ppm)
Alfalfa (leaf and stem)
Barley (foliage)
Barley (roots)
Lettuce (foliage)
Pea (leaf and stem)
0
4
8
16
0
2
4
8
16
0
2
4
8
16
0
2
4
8
16
0
2
4
8
16
0.0
5.3
21.8
27.6
0.0
8.6
11.3
22.8
68.0
0.0
110.0
775.0
1130.0
2030.0
0.0
23.7
33.0
37.0
55.0
0.0
15.1
23.0
31.4
75.3
Source: Adapted from Romney and Childress, 1965, Table 4, p. 213. Reprinted by
permission of the publisher.
TABLE 4.2. BERYLLIUM CONCENTRATION IN BUSH BEANS EXPOSED TO
BERYLLIUM IN NUTRIENT SOLUTIONS
Beryllium content in dry plant tissue
Beryllium content (ppm)
in nutrient
solution (ppm) Roots Stems Leaves Fruit
0.0
0.5
1.0
2.0
3.0
5.0
0
271
431
668
978
1076
0
4
6
15
18
24
0
8
16
34
42
70
0
1
2
4
5
6
Source: Adapted from Romney, Childress, and Alexander, 1962,
Table 1, p. 786. Reprinted by permission of the publisher.
-------
82
when beryllium is in the soluble state. Soils can bind beryllium, affect-
ing uptake. The 7Be isotope was strongly adsorbed by Hanford and Vina
soil and by bentonite, but not kaolinite. Magnesium, barium, or calcium
did not replace beryllium from Hanford and Vina soils or bentonite; these
ions, however, did compete effectively with beryllium for sorption sites
in soil, but not in bentonite. Additions of 40 ppm beryllium to soil
slightly stimulated grass and kale growth, whereas additions of 40 ppm
beryllium to quartz produced severe inhibition (Williams and Le Riche,
1968). Again, most of the beryllium may have been rendered unavailable
for plant uptake because of soil binding. Beryllium (40 ppm added in
soluble form) is more available in acid soils (pH 5.8) than in slightly
alkaline soils (7.5 to 8.0) (Williams and Le Riche, 1968). Although no
uptake data were presented to support this, beryllium significantly re-
duced yield only in the acid soil (Table 4.3).
TABLE 4.3 YIELD OF KALE WITH BERYLLIUM APPLIED AT DIFFERENT
STAGES OF GROWTH
Mean yield per pot of
fresh matter (g)
Soil
Bedfordshire
Hertfordshire
Lincolnshire
Rothamsted
PH
5.8
7.5
7.5
8.0
added (ppm)
0.0
40.0
0.0
40.0
0.0
40.0
0.0
40.0
Application to
large plants
84.5
72.8
167.9
164.4
173.1
172.9
172.1
175.7
Application to
seedlings
110.0
61.9
264.4
300. 3?
288.7
285.8
253.5
258.4
a
P < 0.05.
Source: Adapted from Williams and Le Riche, 1968, Table 2, p. 321.
Reprinted by permission of the publisher.
4.2.2 Translocation
Beryllium is not readily translocated from roots to shoots. Table
4.2 illustrates that most beryllium absorbed from the nutrient solution
is retained within the root, a small amount is translocated to the foli-
age, and still smaller amounts are found in the stems and fruit. A simi-
lar result was obtained when 7Be was supplied for 30 days to bean, barley,
sunflower, and tomato plants (Romney and Childress, 1965). Over 95% of
the activity was found in the roots of each species. Williams and Le Riche
(1968) report low values (7.3 ppm) for the beryllium content in laminae
from leaves of kale grown in nutrient solutions with 10 ppm beryllium.
-------
83
Apparently, though, beryllium may be transported in large amounts to
some plants. Oustrin et al. (1967) found that in maize supplemented with
beryllium sulfate, the highest beryllium concentration (8.1 to 15.7 ppm)
was in the reproductive apparatus. Shoots (2.4 to 2.8 ppm) and roots (2.7
to 2.8 ppm) contained less. Bingham and Steucek (1972) reported that 46%
of the 7Be applied to leaves was absorbed and of that amount, 4% was trans-
ported out of the leaves, presumably through the phloem. They state that
the mobility of beryllium in phloem is similar to that of magnesium and
greater than that of the other alkaline earth elements.
4.2.3 Distribution
There are few data on the beryllium concentration in crop and non-
crop plants. Table 4.4 lists the concentrations reported by several
researchers. Values are in parts per million ash weight; therefore, for
comparison with uptake data and data on toxic levels presented later,
usually given as parts per million dry weight, the ash values should be
divided by ten to give approximate parts per million dry weight estimates.
Where examined, plant concentrations of beryllium are apparently quite
low. Shacklette (1965) states that beryllium is found in only.3.1% of
vascular plant samples (Table 4.3). By examining the concentration of
many elements in bryophytes and vascular plants, he further concluded that
beryllium is present in higher concentrations in vascular plants than in
bryophytes, although the percent of occurrence was greater in bryophytes
(26.3%). This last observation, he suggests, may be due to higher surface
contamination of the bryophytes.
4.2.4 Bioelimination
No data were found suggesting that beryllium is actively eliminated
from living plant material. As with all elements that produce toxic symp-
toms — signifying buildup of that element in the tissue — the death and
abscission of the affected organ eliminates a certain portion of beryl-
lium from the plant.
4.3 EFFECTS
Beryllium typically inhibits plant growth; however, in some cases it
has been reported to stimulate growth. Pea roots increased in fresh weight
when exposed to 10~3 M (^9 ppm) for 20 hr (Gerola and Gilardi, 1955). The
data of Maze and Maze Fils (1939) also suggest that beryllium may give a
slight growth increase in corn. The results of Hoagland (1952a) with toma-
toes in nutrient culture showed that, at pH greater than 9, beryllium at
2 x lO"*1 M slightly decreased growth when magnesium was at adequate levels.
When magnesium was low, 2 x 10"4 M beryllium increased growth above normal-
level magnesium controls. But, beryllium at concentrations of 4 x 10"* M
led to death (dark green leaves and deep purple stems), regardless of the
magnesium concentration; also, at pH values lower than 9, beryllium was
always inhibitory.
Growth inhibition is the more frequent observation in experiments
with beryllium. Romney and Childress (1965) observed that 2 ppm beryllium
-------
84
TABLE 4.4. BERYLLIUM CONTENT IN PLANTS
Beryllium content (ppm)
Plant
Reference
Ash weight
Average
Algae rockweeds
Algae rockweeds
Lichens
Parmelia saxatilis
Xanthoria parietina
Bryophytes
"Vegetation"
Vascular plants
"Angiosperms"
Acacia
Field lupine seeds
Artemisia and
other plants
Zostera
Beans
Cabbage
Nuts
Peanut kernels
Peanut shells
Almond kernels
Almond shells
Tomatoes
0.02-0.54
0-"trace"
0
0
0
0
0
0
.15-2
.10-1
.01-0
.00
.06
.50
.28-1.12
.01-0
.41-0
.03
.52
0.28
0.01
66
<2
h
9
0
0
0
.69
.46
.02
Meehan and Smythe,
Meehan and Smythe,
Fearon, 1935
Shacklette, 1965
Cannon, 1960
Meehan
Meehan
Meehan
and
and
and
Mursaliev,
0
0
0
0
0
0
0
0
.60
.01
.03
.02
.47
.01
.01
.02
Meehan
Meehan
Meehan
Meehan
Meehan
Meehan
Meehan
Meehan
and
and
and
and
and
and
and
and
Smythe ,
Smythe,
Smythe,
1969
Smythe,
Smythe ,
Smythe,
Smythe,
Smythe ,
Smythe,
Smythe,
Smythe,
1967a
1967
1967
1967
1967
1967
1967
1967
1967
1967
1967
1967
1967
a
Sampling sites were in New South Wales, Australia.
Average value for the samples containing beryllium.
or more in nutrient solution reduced fresh weight in peas, soybeans, let-
tuce, and alfalfa. Amounts of beryllium greater than 4% of the cation
exchange capacity of soil reduced yield of beans, wheat, and ladino clover.
Root damage (browning, cessation of elongation, and stubby rootlets) was
observed within one week after addition of 4 ppm beryllium to nutrient
cultures. No chlorosis occurred, but foliage did turn a darker blue green.
The symptoms of beryllium toxicity are not distinct. Table 4.5 sum-
marizes the beryllium toxicity data and symptoms observed (Yopp, Schmid,
and Hoist, 1974). In nutrient solution, toxicity is observed at concen-
trations of about 1 ppm. This leads to extensive beryllium concentration
in roots (Section 4.2.1) and subsequent root damage. Leaves may turn a
darker green and stunted growth may occur. Obviously there is a lack of
data on toxic concentrations and symptoms in a wide variety of species.
-------
TABLE 4.5, PHYTOTOXIC EFFECT EXERTED BY BERYLLIUM ON PLANTS OF ECONOMIC IMPORTANCE IN ILLINOIS
Minimum phytotoxic Plant part Developmental
Plant type Growing medium concentration affected status Symptomatology
Alfalfa Defined nutrient 2.0 ppm Roots, shoots Entire Foliage turns dark green
Barley Defined nutrient 2.0 ppm Roots, shoots Entire Stunted roots and leaves; roots turn brown
and form profuse secondary growth; foli-
age turns dark green as dwarfing intensifies
Bean, bush Defined soil 4% of total cation Shoots Early seedling Stunted growth; early flowering and senescence
type exchange capacity
Bean, bush Defined nutrient 0.5 ppm Shoots, roots Entire Stunting and browning of roots; secondary
root production
Clover, ladino Defined soil 4% of total cation Shoots Early seedling , Stunted growth; early flowering and senescence
type exchange capacity
Corn Defined soil 1.0 ppm Roots, shoots Entire General growth retardation
type 00
ui
Lettuce Defined nutrient 2.0 ppm Shoots, roots Entire Stunting and browning of roots; general
growth depression
Pea, green Defined nutrient 2.0 ppm Shoots, roots Entire Stunting and browning of roots; general
growth depression
Soybean Defined nutrient 2.0 ppm Roots,,. shoots Entire Stunted roots and leaves; roots turn brown
and form profuse secondary growth; foliage
turns dark green as dwarfing intensifies
Tomato Defined nutrient 0.5 ppm Shoots, roots Entire General growth depression
Tomato Defined nutrient 2.0 ppm Shoots, roots Entire Stunting and browning of roots; general
growth depression
Wheat Defined nutrient 2.0 ppm Roots, shoots Entire Stunted roots and leaves; roots turn brown
and form profuse secondary growth; foliage
turns dark green as dwarfing intensifies
Source: Adapted from Yopp, Schmid, and Hoist, 1974, Table 1, pp. 44-45. Data collected from several sources. Reprinted by per-
mission of the publisher.
-------
86
Yellow mottling occurred in rough lemon seedlings exposed to 2 ppm beryl-
lium in nutrient culture (Haas, 1932). Other citrus showed injury at
concentrations above 2.73 ppm; root injury, leaf mottle, and burn were
prevalent. Beryllium increased plant uptake of phosphorus, decreased up-
take of calcium into roots and shoots, and decreased uptake of magnesium
into roots (Romney and Childress, 1965).
The effects of beryllium on specific enzymes have not been well stud-
ied. Hoagland (19522?) observed in vitro that beryllium inhibited plant
phosphatase but not hexokinase. Magnesium, calcium, zinc, and manganese
did not reverse the inhibition. Wallace and Romney (1966) found that beryl-
lium slightly inhibited phosphoenolpyruvate carboxylase and the ribose-5-
phosphate carboxylation sequence (hexose-monophosphate shunt). Beryllium
did not substitute for either the magnesium or manganese requirements of
these enzymes. Slight stimulation of activity with 1 micromole of Be(N03)2
per milliliter (^9 ppm beryllium) occurred in the presence of manganese.
Inhibition of ribose-5-phosphate carboxylation sequence was about 70% for
90 ppm beryllium.
There are several miscellaneous observations on the effects of beryl-
lium. There are two reports on the effects of beryllium on respiration.
Hoist, Schmid, and Yopp (1975) observed that the respiration of excised
barley roots was unaffected by 1000 ppm beryllium even after 18 hr. The
toxic level of beryllium to barley is about 1 ppm. Oxygen consumption
decreased 7.85% in apical roots of pea seedlings treated with 10~3 M beryl-
lium (about 9 ppm) (Gerola and Gilardi, 1955). However, fresh weight and
free and organically bound phosphorus increased in the roots.
Tobacco grown in 1 ppm beryllium nutrient solution contained a sig-
nificantly higher nicotine content than controls; fresh weight increased
slightly (1.8% above control) and tissue beryllium concentration ranged
from 15 ppb to 75 ppm (Tso, Sorokin, and Engelhaupt, 1973). Beryllium
significantly increased the percentage of chromosomal aberrations induced
in barley by ethyl methanesulfonate (Degraeve, 1971).
-------
87
SECTION 4
REFERENCES
1. Bingham, J. D., and G. L. Steucek. 1972. Phloem Mobility of Beryl-
lium in the Bean, Phaseolits vulgaris. Proc. Acad. Sci. 46:16.
2. Cannon, H. L. 1960. Botanical Prospecting for Ore Deposits. Science
132:591-598.
3. Degraeve, N. 1971. Modification des Effects du Methane Sulfonate
d'fithyl au Niveau Chromosomique: I. Les Ions Metalliques (Modifica-
tion of the Effects of Ethyl Methane Sulfonate at the Chromosomal
Level: I. Metallic Ions). Rev. Cytol. Biol. Veg. 34:233-244.
4. Fearon, W. R. 1935. A Classification of the Biological Elements
with a Note on the Biochemistry of Beryllium. Sci. Proc. R. Dublin
Soc. 20:531-535.
5. Gerola, F. M,. and E. Gilardi. 1955. L'azione del Berillio Sull'-
assorbimento del Fosforo e Sull'aumento in Peso di Apici Radicali
(Action of Beryllium on the Absorption of Phosphorus and Increase
in Apial Roots). Atti. Accad. Naz. Lincei Cl. Sci. Fis. Mat. Nat.
Rend. 18:533-538.
6. Haas, A.R.C. 1932. Some Nutritional Aspects in Mottle-Leaf and
Other Physiological Diseases of Citrus. Hilgardia 6:489-495.
7. Hoagland, M. B. 1952a. Beryllium and Growth: II. The Effect of
Beryllium on Plant Growth. Arch. Biochem. Biophys. 35:249-258.
8. Hoagland, M. B. 1952&. Beryllium and Growth: III. The Effect of
Beryllium on Plant Phosphatase. Arch. Biochem. Biophys. 35:259-267.
9. Hoist, R. W., W. E. Schmid, and J. H. Yopp. 1975. Beryllium Absorp-
tion by Excised Barley Roots. Plant Physiol. 56 (Supplement):43,
abstract number 233.
10. Maze, P., and P. J. Maze1 Fils. 1939. Recherches sur la Nutrition
Minerale des Vegetaux Superieurs (Research on the Mineral Nutrition
of Higher Plants). C. R. Soc. Biol. 132:375-378.
11. Meehan, W. R., and L. E. Smythe. 1967. Occurrence of Beryllium as
a Trace Element in Environmental Materials. Environ. Sci. Technol.
1:839-844.
12. Mursaliev, A. M. 1969. Distribution of Some Chemical Elements in
Soils and Plants of the Kirgiz SSR. Rast. Resur. Kirg. (USSR)
1969:74-76. In: Chem. Abstr. 1970. Vol. 73, #130288t.
-------
88
13. Nikonova, N. N. 1971. Plants as Indicators of Beryllium. Biosfere
Primen. Ikh. Sel. Khoz. Med. Sib. Dalinego Vostoka, V. R. Fillipov,
ed. Chem. Abstr. 1973, Vol. 79, #135810 r, pp. 163-166.
14. Oustrin, M. L. , H. Magna, S. Payet, and J. Oustrin. 1967. Etude
de la Toxicite et de la Localisation du Beryllium dans la Culture
de Zea mays (Study of the Toxicity and Localization of Beryllium in
a Culture of Zea mays). Bull. Soc. Hist. Nat. Toulouse 103:344-351.
15. Romney, E. M., and J. D. Childress. 1965. Effects of Beryllium in
Plants and Soils. Soil Sci. 100:210-217.
16. Romney, E. M., J. D. Childress, and G. V. Alexander. 1962. Beryl-
lium and the Growth of Bush Beans. Science 135:786-787.
17. Shacklette, H. T. 1965. Element Content of Bryophytes. U.S. Geo-
logical Survey Bulletin 1198-D, U.S. Government Printing Office,
Washington, B.C. 21 pp.
18. Tso, T. C., T. P. Sorokin, and M. E. Engelhaupt. 1973. Effects of
Some Rare Elements on Nicotine Content of the Tobacco Plant. Plant
Physiol. 51:805-806.
19. Wallace, A., and E. M. Romney. 1966. Effect of Beryllium on In
Vitro Carboxylation Reactions. In: Current Topics in Plant Nutri-
tion, A. Wallace, ed. Edwards Brothers Inc., Ann Arbor, Mich.
pp. 185-188.
20. Williams, R.J.B., and H. H. Le Riche. 1968. The Effect of Traces
of Beryllium on the Growth of Kale, Grass, and Mustard. Plant Soil
(Netherlands) 29:317-326.
21. Yopp, J. H., W. E. Schmid, and R. W. Hoist. 1974. Determination
of Maximum Permissible Levels of Selected Chemicals that Exert Toxic
Effects on Plants of Economic Importance in Illinois. Southern
Illinois University Publication No. PB-237 654, Illinois Institute
for Environmental Quality, Chicago, 111. p. 39-47.
-------
SECTION 5
BIOLOGICAL ASPECTS IN WILD AND DOMESTIC ANIMALS
5.1 SUMMARY
Beryllium uptake by fish varies directly with the beryllium content
of the surrounding medium and, to a lesser extent, with exposure time.
Most of the beryllium may be found in the gastrointestinal tract. Beryl-
lium is more toxic to freshwater fish than lead chloride but less toxic
than pentachlorophenol, cyanide, selenium, or arsenic compounds. Toxic-
ity to fish increases as water hardness decreases, and it appears to be
a result of the effects of beryllium on vital organs, rather than a func-
tion of total beryllium uptake. Preexposure to low levels of beryllium
can increase tolerance to very high concentrations at a later time.
Beryllium inhibits regeneration of amputated limbs in some amphib-
ians. The mechanism of inhibition is unknown, but it is thought to be
related to the influence of beryllium on enzyme activity. Histological
changes in limb stumps treated with beryllium include skin constriction,
absence of blastemata formation, and atypical tissue differentiation.
Embryonic development can also be inhibited by beryllium. Embryos
treated with beryllium have exhibited exogastrulation, spina bifida,
axial defects, hemicephaly, and abnormal development of the central ner-
vous system.
/
Beryllium is eliminated rapidly by dairy cattle, with 68% of an oral
dose being excreted within 83 hr. More than 90% of the oral dose is
excreted in feces; milk contains less than 0.002%. The small amount of
absorbed beryllium is deposited in the liver, kidney, and skeletal system.
5.2 AQUATIC ORGANISMS
5.2.1 Metabolism; Uptake and Distribution
Radioberyllium studies (Slonim and Damm, 1972; Slonim and Slonim,
1973) have shown that beryllium uptake by guppies (Lebistes reticulatus)
varies directly with the beryllium concentration of the surrounding medium
and, to a lesser extent, with the length of exposure. Total uptake is not
influenced by fish age, NaHC03_ buffered solutions, or water hardness.
Slonim and Damm (1972) found that beryllium levels in guppies are highest
in the gastrointestinal tract, followed by kidneys and ovaries. The low-
est amounts were found about equally in gills, liver, brain, heart, eye,
and spleen.
5.2.2 Effects
5.2.2.1 Physiological Effects — Beryllium solutions inhibit regeneration
of amputated limbs in some amphibians. The mechanism of inhibition is not
known, but it may be related to the influence of beryllium on the activity
89
-------
90
of enzymes, particularly those which are magnesium dependent (Tapper, 1972)
In salamander (Ambystoma opaoum and A. maculatwii) larvae, the extent of
inhibition is related to larval size and to the amount of limb amputated
(Thornton, 1949). A solution of N/7 beryllium nitrate applied to the limb
stump of small larvae completely inhibited regeneration regardless of the
amputation site. In larger larvae, the treatment inhibited regeneration
following amputation through the upper arm, but not the forearm. Regenera-
tion of the forearm was suppressed by tripling the beryllium dose.
Inhibition of regenerating Arribystoma limbs occurs only if beryllium
is present in the limb tissues at the time of amputation (Thornton, 1950).
The beryllium reaction was localized within 0.5 mm of the wound surface,
and removing the beryllium-inhibited stump stimulated normal regeneration.
Histological changes in limb stumps following beryllium treatment included
skin constrictions, absence of blastemata formation, and atypical tissue
differentiation (Thornton, 1951).
Scheuing and Singer (1957) amputated the upper arm of adult newts
(Tritwnts sp.) and infused the regenerating blastemata with 0.001 to 0.1 M
beryllium nitrate (Table 5.1). Concentrations of 0.1 M or more suppressed
regeneration and caused tissue destruction, while concentrations of 0.001 M
had no effect. Bone, muscle, and fibrous connective tissue were the most
sensitive to beryllium; nerves and epidermis were the most resistant. Sup-
pressed regeneration in newt limbs treated with beryllium has also been
reported by Carlson (1970).
The development of eggs and tadpoles of the common frog (Ecma tempo-
vavia) was retarded by beryllium nitrate treatment (Needham, 1941) (Table
5.2). The early gastrula period was especially susceptible. Overall detri-
mental effects included exogastrulation, spina bifida, axial defects, hemi-
cephaly, and microcephaly. The same treatment retarded regeneration of
newt limbs and tails and halves of planaria (Polyoelius nigra).
Beryllium sulfate acts as a mitotic suppressor in snail (Lyrmaea sp.)
embryos (Bose, 1973). After treatment with 50 yg/ml beryllium sulfate,
uncleared egg masses developed to the trochophore stage but did not develop
normally after this stage. When a solution containing 100 yg/ml beryllium
sulfate was used, normal development was scarce, and at 500 ug/ml mortality
was quite high.
An injection of 0.02 cc of a 5% suspension of beryllium hydroxide into
unamputated newt forelimbs resulted in the formation of accessory limbs
(Breedis, 1952). Carlson (1970), however, was unable to produce accessory
limbs after injecting the same species with N/7 beryllium nitrate.
5.2.2.2 Toxic Effects - Tarzwell and Henderson (1960) determined the 96-hr
median tolerance limit (TLSo) of fathead minnows and bluegill to several
metals (Table 5.3). Beryllium was the most toxic of the less common metals
tested; for fathead minnows the TL5o in soft water was 0.2 mg/liter. Beryl-
lium sulfate toxicity to freshwater fish was tested by Cardwell et al.
(1976) (Tables 5.4, 5.5, and 5.6). Beryllium was more toxic than lead
chloride but less toxic than pentachlorophenol, cyanide, selenium, or
arsenic compounds. Susceptibility to beryllium decreased in the following
-------
TABLE 5.1. EFFECTS OF Be(N03)2-3H20 ON REGENERATION OF LIMBS IN ADULT TRITVRUS
Molar
concentration
of beryllium ion
0.1
0.015
0.01
0.0075
0.001
Infusion
time
(hr)«
5
3
1-2
4
2-6
4
4
Age of regenerate
(days after
amputation)
12
12
12
3
6
9
10
12
13-15
16-18
12
12
12
Stage of
regeneration
Early bud
Early bud
Early bud
Wound healing
Wound healing
Wound healing
Very early bud
Early bud
Medium bud
Late bud
Early bud
Early bud
Early bud
Number of
animals
20
5
20
5
8
6
8
15
8
8
76
5
7
Resorption after infusion Regeneration
Extensive
20
5
16
0
3
0
0
3 '
0
0
5
0
0
Slight^7
0
0
2
4
2
6
3
8
8
8
21
0
0
Absent
0
0
1
1
5
0
5
4
0
0
50
5
7
Absent
20
5
18
4
5
6
3
11
8
8
26
0
0
after infusion
o
Present
0
0
2
1
3
0
5
4
0
0
50
5
7
Infusion at the rate of 0.0013 ml/hr.
Both regenerate and stump involved. In most instances, resorption set in after an initial delay of seven to ten days; in other
cases it was earlier.
Confined to regenerate.
Includes those showing resorption.
eMost regenerates were heteromorphic, and some appeared only after a delay of one to two months.
Source: Scheuing and Singer, 1957, Table 1, p. 303. Reprinted by permission of the publisher.
-------
92
Stage
TABLE 5.2. RESULTS OF TREATMENT OF FROG EMBRYOS WITH BERYLLIUM
(3-hr treatment except as stated)
ff/3 beryllium
N/7 beryllium
ff/14 beryllium
2-4 cells
20 cells
64 cells
128 cells
Mid blastula
Late blastula
Late blastula
(jelly removed)
Early gastrula
Mid gastrula
Late gastrula
Neurula
High mortality
No mortality, few
abnormals among
survivors
80% mortality, axial
abnormals among
survivors
1002 mortality in
2 hr, survivors
abnormal*2
All dead neurula,
great abnormalities
2 hr, low mortality,
great abnormality
Dead before hatching,
axial abnormalities
No mortality,
abnormalities slight
30% mortality,
abnormalities slight
80% mortality,
survivors abnormal
High mortality
No mortality, normal
survivors
Low mortality, 80%
axial abnormals
among survivors
50% mortality, all
survivors abnormal
1 hr, 95% mortality;
1/2 hr, 30% mortality
All dead tail bud
stages, great
abnormalities
2 hr, no mortality,
all abnormal; 3 hr,
90% mortality
Low mortality, 20%
axial abnormalities
No mortality,
abnormalities slight
High mortality
No mortality, normal
survivors
No effect
Low mortality, few
abnormalities
All dead late tail bud
stage, abnormalities
2 hr, no mortality, few
abnormalities
48 hr, no effect
No mortality, all normal
Tail bud hatching
External gills
Internal gills
No effect
4 hr, fatal
2 1/2 hr, fatal
No effect
4 hr, not fatal
5-6 hr, fatal
No effect
14 hr, fatal
6-8 hr, fatal
See Needham, 1941.
Source: Needham, 1941, Table 1, p. 61.
Reprinted by permission of the publisher.
order: fathead minnow, flagfish fry, goldfish, brook trout, and channel
catfish. The median lethal concentrations determined by Cardwell et al.
(1976) were 1.5 to 7 times higher than those of Slonim (1973) and Slonim
and Slonim (1973). The difference is probably due to the intermittent
flow system with toxicant renewal used by Cardwell et al. (1976) as op-
posed to the static bioassays of the latter authors.
Beryllium toxicity to fish increases as water hardness decreases.
This is partially due to the increased buffering capacity of hard water
and the antagonism of calcium to beryllium (Slonim, 1973). Also, beryl-
lium may penetrate to vital organs more readily in soft water. Beryllium
toxicity is not a function of total beryllium absorbed as much as it is
-------
93
TABLE 5.3. THE 96-HR MEDIAN TOLERANCE LIMITS (TL50) OF SEVERAL LESS COMMON METALS TO FISH
(rag/liter of metal ion)
Compound
Antimony potassium tartrate (2KSbOCi4H1
Antimony trichloride (SBClg)
Antimony trioxide (Sb2C>3)
Beryllium chloride (BeCl2)
Beryllium nitrate [ Be(N03)2- 3H20]
Beryllium sulfate (BeS(V4H:0)
Cadmium chloride (CdClr -2. 5H20)
Copper sulfate (CuSOi,- 5H20)
Lead chloride (PbCl?)
Molybdic anhydride (Mo03)
Nickelous chloride (NiCl2-6H:0)
Titanium sulfate [Ti2(SOtl)3]
Uranyl acetate [U0r (C2H302) 2 -2H20]
Uranyl nitrate [U02 (N03)2 -6HnO]
Uranyl sulfate (U02SO[,- 3H20)
Vanadium pentoxide (V?05)
Vanadyl sulfate (VOSOi,)
Zirconium oxychloride (ZrOClj -6H70)
Zirconium sulfate [Zr(SOi4)2-4H20]
Fathead
Soft water
,06-H20) 20
9
>80
0.15
0.15
0.2
0.9
0.05
2.4
70
4
8.2
3.7
3.1
2.8
13
4.8
18
14
TL5B
minnow Bluegill
Hard water Soft water Hard water
12
17
>80
15
20
11 1.3 12
5
1.4 0.2 10
>75
370
24
120
135
55
30 b 55
240 15 270
145
Source: Adapted from Tarzwell and Henderson, I960, Table 1, p. 12. Reprinted by permission of the
publisher.
TABLE 5.4. MEDIAN LETHAL CONCENTRATIONS (LC50) AND
MEDIAN LETHAL TIMES (LT50) FOR FLAGFISH FRY
EXPOSED TO BERYLLIUM SULFATE
Group
Median response
estimate
95% confidence
limits
96-hr LC50 (rag/liter BeSO^)
I
II
III
I
II
III
46.3
41.1
41.1
LT50 (hr) for 47.8 ±
41.3
74.8
55.4
43.9-48.8
37.2-45.3
38.4-44.0
2.2 mg/liter BeSO^
10.5-162.1
61.1-91.4
48.3-63.5
Source: Adapted from Cardwell et al., 1976,
Appendix Table 41, p. 115.
-------
94
TABLE 5.5. MEDIAN LETHAL CONCENTRATIONS (LC50)
FOR JUVENILE GOLDFISH EXPOSED TO
BERYLLIUM SULFATE
Exposure
time
(hr)
96
120
168
186
216
240
(mg/liter)
55.9
49.3
48.3
46.5
41.6
38.4
95% confidence
limits for LC50
(mg/liter)
49.0-63.7
44.0-55.3
42.7-54.6
40.8-53.1
37.2-46.6
34.4-43.0
aAs
Source: Adapted from Cardwell et al., 1976,
Appendix Table 42, p. 116.
TABLE 5.6. MEDIAN LETHAL CONCENTRATIONS
(LC50) FOR JUVENILE FATHEAD MINNOWS
EXPOSED TO BERYLLIUM SULFATEa
Exposure
time
(hr)
92
96
121
164
192
283
336
LC50
(mg/liter)
40.2
37.9
30.8
27.7
27.4
26.1
25.4
95% confidence
limits for LCsg
(mg/liter)
27.6-58.5
27.5-52.3
29.4-32.3
26.1-29.3
25.9-29.0
24.4-27.9
23.9-27.0
aAt a concentration of 47.8 mg/liter,
the median lethal time was 75 hr.
2>As BeSOi,.
Source: Adapted from Cardwell et al.,
1976, Appendix Table 40, p. 114.
-------
95
the result of the effect of beryllium on a particular organ. Slonim (1973)
and Slonim and Slonim (1973) found that beryllium sulfate was 100 times
as toxic to the common guppy (Lebistes retioulatus) in soft water as in
hard water (Table 5.7). A 55-fold difference in toxicity between soft
and hard water was reported for fathead minnows by Tarzwell and Henderson
(1960). Acute toxicity of beryllium sulfate to salamander larvae was
investigated by Slonim and Ray (1975) in a static bioassay (Table 5.8).
The 96-hr TL50 was 20.3 mg/liter in hard water and 0.19 mg/liter in soft
water.
TABLE 5.7. MEDIAN TOLERANCE LIMITS OF GUPPIES TO
BERYLLIUM SULFATE IN WATER OF
VARYING HARDNESS
Water
hardness
(mg/liter)
400
275
150
22
Median tolerance limit (mg/liter Be2+)
24 hr
22.0
14.0
6.8
>2
48 hr
22.0
13.7
6.8
0.32
96 hr
20.0
13.7
6.1
0.16
Source: Slonim and Slonim, 1973, Table 2, p. 297.
Reprinted by permission of the publisher.
TABLE 5.8. MEDIAN TOLERANCE LIMITS OF SALAMANDERS TO
BERYLLIUM SULFATE BY GRAPHIC INTERPOLATION
(in mg beryllium per liter)
Bioassay
A
B
C
D
Mean
Hard water
24
31
31
18
21
25
hr
.5
.5
.2
.2
.60
48
31.
31.
18.
18.
24.
hr
5
5
2
2
85
96
31
31
18
18
24
hr
.5
.5
.2
.2
.85
Soft water
24 hr 48 hr 96
23.7 4.21 3.
8.83 4.21 3.
>10 >10 8.
>10 >10 8.
>12 >7 5.
hr
15
15
02
32
65
Source: Slonim and Ray, 1975, Table 2, p. 309. Reprinted
by permission of the publisher.
-------
96
Slonim (1973) showed that preexposure conditioning of guppies to low
levels of beryllium sulfate significantly increased their tolerance to very
toxic concentrations (Table 5.9). Each concentration in the first column
of Table 5.9 represents a 20-fold increase in the beryllium level at which
the fish were preexposed. These data indicate that fish may be able to
develop a limited tolerance to beryllium.
TABLE 5.9. ACUTE TOXICITY OF BeSO,, SOLUTIONS TO UNEXPOSED AND PREVIOUSLY EXPOSED GUPPIES
Unexpojed fish
Be2+
concentration
(mg/liter)
2a
5
100
200
4
14
40
20
80
Water
hardness
-(rag/liter)
24
24
400
400
80
80
80
200
200
Number of
fish
10
10
10
10
10
10
10
10
10
Mean
survival
time
(hr)
28.9
27.3
8.38
3.13
11.8
17.6
8.90
19.2
7.43
Preexposed fish
Preexposure
period
(days)
14
14
14
14
159
159
159
159
159
Number of
fish
8
8
10
10
7
4
3
7
6
Mean
survival
time
(hr)
41.2
41.8
9.37
3.98
18.7
10.3
8.92
20.6
6.55
a
Source: Slonim, 1973, Table V, p. 2117. Reprinted by permission of the publisher.
5.3 BIRDS
5.3.1 Metabolism: Uptake and Distribution
Data concerning uptake and distribution of beryllium in birds are very
limited. This is not unusual, considering that beryllium is not commonly
found in significant concentrations in the natural environment (Section
7.3). In the only study located, Baker et al. (1976) found no beryllium
in liver, muscle, or brain tissue of seven species of waterfowl sampled in
New York. The limit of detection was 1.0 yg/g.
5.3.2 Effects
5.3.2.1 Physiological Effects — Palmer (1972) found that beryllium sulfate
inhibits embryonic development of chicks (Callus gallus). In this study,
eggs were injected with beryllium sulfate 24 to 48 hr after incubation and
sacrificed between 60 and 216 hr after incubation. Injections early in
embryonic development affected heart formation; injections at later stages
produced deformities in the intestinal tract and calcification of bone
structures. Limb bud formation was affected, and the central nervous sys-
tem developed abnormally. Compression of the brain and eyes as a result
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97
of defective skull growth probably caused the central nervous system abnor-
malities. Inhibition of the alkaline phosphatase system was suggested as
a possible explanation for most of the abnormalities resulting from beryl-
lium injections.
5.3.2.2 Toxic Effects — Chanh and Maciotta-Lapoujade (1966) studied the
effects of beryllium sulfate on pigeons and chickens. The beryllium was
administered as a profusion timed at flow rates to produce death of the
subject in about 60 min. Chickens were about three times as sensitive as
pigeons, with the lethal doses averaging 0.56 ± 0,15 g/kg and 1.49 ± 0.16
g/kg, respectively.
5.4 MAMMALS
5.4.1 Metabolism
5.4.1.1 Uptake and Distribution — Radioberyllium distribution in cows
was studied by Mullen et al. (1972). A lactating dairy cow received an
intravenous injection of 2.7 mCi of 7BeCl2 and was sacrificed after 119
hr (Table 5.10). In addition, three calves were given oral doses of 0.76,
0.70, and 1.3 mCi 7BeCl2 and were sacrificed at 71, 140, and 454 hr,
respectively (Table 5.11). The results indicate that the liver, kidney,
and skeletal system of cows accumulate most of the absorbed beryllium.
5.4.1.2 Elimination — Mullen et al. (1972) found that radioberyllium
administered orally to cows was rapidly eliminated. Sixty-eight percent
of the administered dose was excreted in the feces, urine, and milk path-
ways in the first 83 hr. Feces contained over 90% of the excreted beryl-
lium, while milk contained less than 0.002%. The biological half-time as
measured in milk was 19 hr. A cow injected intravenously x^ith a single
dose of beryllium excreted 18% of the total dose within 91 hr; 96% was in
urine, 2% in feces, and the remainder in milk. The half-time of beryllium
in this case as measured in milk was 40 hr. Thus, any health hazard to
man resulting from ingestion of dairy products under normal circumstances
appears to be slight.
5.4.2 Physiological and Toxic Effects
No data regarding the physiological or toxic effects of beryllium on
mammals other than those used as human models were located in the litera-
ture. For a discussion of beryllium effects on mammals used as models,
see Section 6.
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98
TABLE 5.10. RECOVERY OF 7Be IN TISSUES OF A COW 119 HOURS AFTER
INTRAVENOUS ADMINISTRATION
(The values listed are percentages of dose, decay-corrected
to time of administration.)
Tissue
Abomasal contents
Abomasal tissue
Adrenal
Blood
Bone (compact)
Brain
Eye
Fat
Gall bladder
Hair, no skin
Heart
Kidney
Large intestine contents
Large intestine tissue
Liver
Lung
Muscle
Omasal contents
Omasal tissue
Ovaries
Pancreas
Parotid
Reticulum tissue
Rib
Rumen reticulum contents
Rumen tissue
Skin with hair
Skin, no hair
Small intestine contents
Small intestine tissue
Spleen
Thyroid
Total
Concentration
(%/kg)
0.023
0.067
0.098
0.020
0.304
0.002
0.031
0.005
0.058
<0.001
0.041
1.03
0.016
0.020
1.15
0.054
0.007
<0.001
0.083
0.141
0.160
0.072
0.017
0.354
<0.001
0.023
0.013
0.019
0.005
0.028
0.100
0.045
Recovery
(% in organ or compartment)
0.080
0.161
0.004
9.44
21.6
<0.001
<0.001
0.682
0.006
<0.001
0.143
1.41
0.131
0.054
14.0
0.483
1.43
<0.001
0.083
0.005
0.054
0.001
0.033
0.007
0.261
0.470
0.023
0.213
0.133
<0.001
50.9
An estimated 49% of the administered dose had been excreted
by the time of sacrifice.
Source: Mullen et al., 1972, Table 1, p. 20. Reprinted by permis-
sion of the publisher.
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99
TABLE 5.11. RECOVERY OF 7Be IN TISSUES OF THREE CALVES AFTER A SINGLE ORAL DOSE
(The values listed are percentages of dose, decay-corrected to time of administration.)
Tissue
Abomasal contents
Abomasal tissue
Adrenal
Blood
Bone (compact)
Brain
Eye
Fat
Gall bladder with bile
Hair
Heart
Kidney
Large intestine contents
Large intestine tissue
Liver
Lung
Muscle
Omasal contents
Omasal tissue
Pancreas
Parotid
Reticulum tissue
Rib
Rumen reticulum contents
Rumen tissue
Skin with hair
Skin, no hair
Small intestine contents
Small intestine tissue
Spleen
Thyroid
Thymus
Total
Concentration
(%/kg)
71 hra
0.275
0.045
<0.001
<0.001
<0.001
<0.001
<0.001
<0.001
<0.001
0.299
<0.001
0.004
0.083
0.010
0.002
<0.001
<0.001
1.85
0.101
0.001
<0.001
0.048
0.011
0.110
0.100
0.029
0.002
0.150
0.022
<0.001
<0.001
190 hra
0.002
<0.001
<0.001
0.002
<0.001
<0.001
<0.001
<0.001
<0.001
0.022
<0.001
oiooe
0.034
0.001
0.003
<0.001
<0.001
0.052
0.001
0.001
<0.001
0.016
0.025
0.036
0.019
0.011
<0.001
0.016
0.034
<0.001
<0.001
454 hr2
<0.001
0.001
<0.001
<0.001
0.020
<0.001
<0.001
<0.001
<0.001
0.012
<0.001
0.002
0.003
<0.001
0.001
<0.001
<0.001
0.005
<0.001
0.002
<0.001
<0.001
0.004
<0.001
<0.001
0.001
<0.001
0.002
0.004
<0.001
<0.001
<0.001
Recovery
(% in organ or compartment)
71 hra
0.145
0.013
<0.001
<0.001
<0.001
<0.001
<0.001
<0.001
<0.001
<0.001
0.002
0.381
0.012
0.006
<0.001
0.026
0.099
0.038
0.001
<0.001
0.012
;
4.72
0.124
0.285
0.167
0.074
<0.001
<0.001
6.10
190 hra
0.002
0.003
<0.001
0.012
0.142
<0.001
<0.001
<0.001
<0.001
<0.001
0.002
0.015
<0.001
0.005
0.001
<0.001
0.010
<0.001
< 0.001
<0.001
0.004
0.141
0.020
0.061
0.028
0.062
<0.001
<0.001
0.508
454 hra
<0.001
<0.001
<0.001
0.001
0.264
<0.001
<0.001
0.002
<0.001
<0.001
<0.001
<0.001
<0.001
0.006
<0.001
<0.001
0.001
<0.001
<0.001
<0.001
<0.001
<0.001
<0.001
0.007
0.003
0.011
<0.001
<0.001
<0.001
0.295
Time after administration when calf was sacrificed.
Source: Mullen et al., 1972, Table 2, p. 21. Reprinted by permission of the publisher.
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100
SECTION 5
REFERENCES
1. Baker, F. D., C. F. Tumasonis, W. B. Stone, and B. Bush. 1976.
Levels of PCB and Trace Metals in Waterfowl in New York State. N.Y.
Fish Game J. 23:82-91.
2. Bose, T. 1973. Effects of Beryllium Sulphate on Embryonic Develop-
ment and Rhythmic Pattern of Subsequent RNA-Synthesis in Lyrnnae sp.
Indian J. Exp. Biol. (India) 11:538-540.
3. Breedis, C. 1952. Induction of Accessory Limbs and of Sarcoma in
the Newt (Tritwms v-iridescens) with Carcinogenic Substances. Cancer
Res. 12:861-866.
4. Cardwell, R. D., D. G. Foreman, T. R. Payne, and D. J. Wilbur. 1976.
Acute Toxicity of Selected Toxicants to Six Species of Fish. EPA-
600/3-76-008, U.S. Environmental Protection Agency, Washington, D.C.
117 pp.
5. Carlson, B. M. 1970. The Effect of X-irradiation and Beryllium
Nitrate upon Impant-induced Supernumerary Limb Formation in the
Newt. Oncology (Switzerland) 24:31-47.
6. Chanh, P.-H., and M. Maciotta-Lapoujade. 1966. Toxicite Immediate
du Sulfate de Beryllium a L'egard eu Pigeon et du Poulet (Acute
Toxicity of Beryllium Sulfate on Pigeons and Chicks). Agressologie
(France) 7:597-601.
7. Mullen, A. L., R. E. Stanley, S. R. Lloyd, and A. A. Moghissi. 1972.
Radioberyllium Metabolism by the Dairy Cow. Health Phys. (Great
Britain) 22:17-22.
8. Needham, A. E. 1941. Some Experimental Biological Uses of the
Element Beryllium (Glucinum). Proc. Zool. Soc. London (Great Britain)
111:59-85.
9. Palmer, S. E. 1972. Chick Embryo Deformities Produced by Beryllium
Toxicity. J. Miss. Acad. Sci. 17:78.
10. Scheuing, M. R., and M. Singer. 1957. The Effects of Microquanti-
ties of Beryllium Ion on the Regenerating Forelimb of the Adult Newt,
Triturus. J. Exp. Zool. 136:301-327.
11. Slonim, A. R. 1973. Acute Toxicity of Beryllium Sulfate to the
Common Guppy. J. Water Pollut. Control Fed. 45:2110-2122.
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101
12. Slonim, A. R., and F. C. Damm. 1972. Beryllium Uptake by the Common
Guppy Using Radioisotope 7Be: II. Beryllium Concentration in Fish.
AMRL-TR-72-95, Aerospace Medical Research Laboratory, Wright-Patterson
Air Force Base, Ohio. 24 pp.
13. Slonim, A. R., and E. E. Ray. 1975. Acute Toxicity of Beryllium
Sulfate to Salamander Larvae (Ambystoma spp.). Bull. Environ.
Contarn. Toxicol. 13:307-312.
14. Slonim, C. B., and A. R. Slonim. 1973. Effect of Water Hardness on
the Tolerance of the Guppy to Beryllium Sulfate. Bull. Environ.
Contain. Toxicol. 10:295-301.
15. Tarzwell, C. M., and C. Henderson. 1960. Toxicity of Less Common
Metals to Fishes. Ind. Wastes (Chicago) 5:12.
16. Tepper, L. B. 1972. Beryllium. In: Metallic Contaminants and
Human Health, D.H.K. Lee, ed. Academic Press, New York. pp. 127-137.
17. Thornton, C. S. 1949. Beryllium Inhibition of Regeneration: I.
Morphological Effects of Beryllium on Amputated Fore Limbs of Larval
Amblystoma. J. Morphol. 84:459-493.
18. Thornton, C. S. 1950. Beryllium Inhibition of Regeneration: II.
Localization of the Beryllium Effect in Amputated Limbs of Larval
Amblystoma. J. Exp. Zool. 114:305-333.
19. Thornton, C. S. 1951. Beryllium Inhibition of Regeneration: III.
Histological Effects of Beryllium on the Amputated Fore Limbs of
Amblystoma Larvae. J. Exp. Zool. 118:467-493.
-------
SECTION 6
BIOLOGICAL ASPECTS IN HUMANS
6.1 SUMMARY
Beryllium exposure is primarily an industrial problem, but it is to
some extent an environmental problem in the vicinity of industrial sources.
The metal enters the body by inhalation, ingestion, and skin absorption,
with inhalation the primary route. Once inhaled, beryllium is retained
in the lungs and slowly mobilized from the lungs into the blood. Beryl-
lium is minimally absorbed from the gastrointestinal tract; consequently,
ingested beryllium presents little health hazard.
The metal is transported through the body by the blood and lymph and
then deposited in various tissues. Beryllium storage is of long duration,
especially in pulmonary lymph nodes and bone. The skeleton is the ulti-
mate storage site. Since little beryllium is absorbed from the digestive
tract, that which accumulates in body tissue is from inhalation.
Urinary excretion is an indication of past exposure, and the excre-
tion rate is related to the solubility of the inhaled compound. Ingested
soluble beryllium is only slightly absorbed through the intestines; hence,
urinary excretion of ingested beryllium is minimal. Ingested beryllium
is excreted primarily in the feces.
Persons exposed to beryllium by inhalation can develop a respiratory
disease, which may be either acute or chronic in form. Dermatitis and/or
skin ulcers may develop as a result of direct skin contact. These effects
have been caused by the metal and its compounds; no detectable illness has
been caused by beryl ore. The standard for exposure of industrial workers
to beryllium is 2 vg of total airborne particulate beryllium per cubic me-
ter of air over an 8-hr work day. In neighborhoods near beryllium sources,
0.01 yg of beryllium per cubic meter as an average monthly concentration
is permissible.
Acute beryllium disease is defined as that lasting less than one
year. Disease severity appears dependent on amount of exposure, toxicity
and concentration of the compound, and individual susceptibility. When
exposed to large amounts of soluble salts, the disease can be rapidly fa-
tal. The acute disease may be expressed as contact or allergic dermati-
tis, skin ulcers, conjunctivitis, and respiratory effects. Respiratory
effects appear as nasopharyngitis, tracheobronchitis, and acute chemical
pneumonitis. Experimentally, liver necrosis, central nervous system
changes, and anemia have been produced by beryllium exposure in labora-
tory animals.
Chronic beryllium disease usually arises from inhalation exposure,
although in a few cases, direct skin contact was stated as the cause. The
chronic form can have a latent period of more than 20 years, is progres-
sive in severity, and is a systemic disease. In some instances, the acute
102
-------
103
form may progress to the chronic form. The dose level necessary to induce
the chronic form is not known. It has been proposed that disease onset
involves some form of stress, such as surgery, infection, or pregnancy,
which leads to altered adrenal function resulting in beryllium transloca-
tion to organs critical in systemic disease initiation. This form of the
disease is not always easily diagnosed because of lack of specific clini-
cal criteria. A history of beryllium exposure must be established before
diagnosis can be confirmed. A common cause of death is from the compli-
cation of cor pulmonale with myocardial decomposition. Besides occurring
among industrial workers, chronic beryllium disease has been found among
residents in the near vicinity of a plant, usually within 3/4 mile of the
point source. These cases arise from inhalation of airborne beryllium
carried from the plant or from direct contact from handling workers' con-
taminated clothing. Treatment consists of steroid and adrenocorticotropic
hormone administration.
Experimental findings show that some beryllium compounds are carci-
nogenic in experimental animals. Pulmonary cancer has been produced in
rats and monkeys by inhalation exposure. Sarcomas have also been induced
in rabbits by injection. Cancer has been reported among beryllium workers;
however, a direct relationship has not been proven. Epidemiological stud-
ies have failed to show a correlation between exposure and cancer incidence.
6.2 METABOLISM
6.2.1 Uptake and Absorption
Beryllium enters the body by inhalation, ingestion, and skin absorp-
tion. Inhalation is the primary route of uptake, with beryllium gaining
access to the body through the lungs (Berry, Osgood, and St. John, 1974).
Following inhalation exposure, the metal is retained in the lungs and
slowly mobilized (Beliles, 1975) by absorption from the lungs into the
blood.
Following intratracheal injection, 7BeSO«, in trace amounts was either
retained in the lungs of rats for long periods or mobilized after 16 days;
7Be citrate (a soluble, nonionizing complex) was completely mobilized after
four days (Van Cleave and Kaylor, 1955). In the amount of 10 Ci, 7BeCl2
showed a pulmonary halftime of 20 days; 18% of the dose accumulated in the
bones in 147 days (Kuznetsov, Matveev, and Suntsov, 1974).
Uptake by ingestion and skin absorption cpntributes negligible amounts
of beryllium to the total body burden. Skin absorption of beryllium, even
through repeated or prolonged contact, adds only insignificant quantities
to the body (Berry, Osgood, and St. John, 1974). Resorption of trace levels
of 7BeCl2 through rat tail, with subsequent systemic distribution was re-
ported by Petzow and Zorn (1974). Absorption of beryllium from the gastro-
intestinal tract is minimal (Schroeder and Mitchener, 1975Z?). The amount
of beryllium absorbed from the stomachs of guinea pigs given beryllium sul^
fate orally was small and varied from animal to animal (Hyslop et al., 1943).
Most of a daily dose of 0.6 to 6.6 yg of beryllium ingested by rats passed
through the gastrointestinal tract unabsorbed because it was precipitated
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104
in the intestines as the phosphate (Reeves, 1965). Furchner, Richmond, and
London (1973) showed that less than 1% of an oral dose of 7Be was absorbed
from the gut of mice, rats, monkeys, and dogs.
6.2.2 Transport, Distribution, and Accumulation
6.2.2.1 Transport — Beryllium is transported by the blood and lymph from
the site of deposition; in humans this site is usually the lungs and occa-
sionally the skin. In vitro studies using artificial serum indicated the
beryllium forms transported by the body fluids were the orthophosphate and
hydroxide (Reeves and Vorwald, 1961). The principal form is thought to be
the orthophosphate colloid, with 2% to 3% as the colloidal oxide (Stokinger,
1972). Following intravenous injection of beryllium sulfate in rats, the
circulating beryllium was almost completely in the plasma (Vacher and Stoner,
1968Z?) . The beryllium existed in two forms: a small fraction of small
molecular size representing a diffusible form associated with the plasma
organic acids and the bigger fraction in aggregates of beryllium phosphate.
These aggregates were weakly bound to plasma protein, probably a-globulin.
Beryllium transport is governed by the physiochemical state of the
metal rather than by differences in species metabolism (Stokinger, 1972).
A significant portion of beryllium transported in blood is carried to the
skeleton, irrespective of route of administration or beryllium form. The
ionic form of the remaining beryllium goes directly to the kidney, whereas
the colloidal form is carried first to the liver.
6.2.2.2 Distribution and Accumulation — Beryllium in the body is ultimately
stored in bone. The distribution of beryllium in patients with beryllium
disease has not been well defined and does not necessarily duplicate that
in animals, since humans appear to retain a body burden of beryllium longer
than the life of experimental animals (Tepper, Hardy, and Chamberlin, 1961).
It must also be realized that the presence of beryllium in tissue indicates
exposure but does not indicate the presence of beryllium disease (Tepper,
1972a).
6.2.2.2.1 Tissue concentration — Beryllium storage in tissues is of long
duration, especially in pulmonary lymph nodes and bone (Stokinger, 1972),
with the ultimate site of beryllium storage in the skeleton (Van Cleave
and Kaylor, 1955). In human pulmonary tissue, amounts less than 2 yg/100 g
(dry weight basis) are not regarded as indicative of occupational exposure;
in exposed workers, the levels may be as high as several mg/100 g. Small
quantities of beryllium which pass the kidney are diffusible and are asso-
ciated with organic acids such as citrate (Tepper, 1972a).
Analysis of lung tissue for beryllium has shown that there is no cor-
relation between beryllium concentration and intensity of disease (Preuss,
1975). Therefore, great variability exists in beryllium distribution in
different stages of beryllium disease. This variability is demonstrated
in Table 6.1; within an individual there is little correlation between
beryllium concentration levels in various tissues. From these data it
appears that beryllium is distributed throughout the lung. Sumino et al.
(1975) reported low beryllium values of 0.01 to 0.03 yg per gram of wet
tissue in the lungs of Japanese.
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105
TABLE 6.1. TISSUE DISTRIBUTION OF BERYLLIUM
(in microgr.ims per 100 R of tissue)
Organ
Lung
Right upper lobe
Apical segment
Posterior segment
Anterior segment
Right middle lobe
Lateral segment
Medial segment
Right lower lobe
Apical segment
Medial basal segment
Anterior basal segment
Lateral basal segment
Left upper lobe
Anterior segment
Apical-posterior segment
Superior lingular segment
Inferior lingular segment
Left lower lobe
Apical segment
Anterior basal segment
Lateral basal segment
Posterior basal segment
Lymph node
Hilar
Tracheobronchial
Liver
Kidney
Spleen
Myocardium
Brain
Bone
Case Case Case Case
7 77 176 178
3.
1.
2.
1.
- 1.
2.
2.
2.
10.
1.
12.0 3.8
0.1
2
6
1
2
0.3
8
4
5
5
2 4.2
1
0.5
8.4 0.1 0.1
27.2 0.0 0.2
4.3 0.3 0.1
0.1
X
13.5
Case Case
286 314
0.2
16.0
9.5
0.1
7.9
0.6
0.7 8.
28.2
0.1 18.
4.
15.4 11.
7.
9.8 4.
4.0 4.
12.
0.
0.
0.
<0.
8
0
6
6
0
5
8
0
1
1
1
02
Case Case Case Case
439 467. 610 617
18.4
15.2
440
0
0
0
1
0
0
0
0
600 18.0 8
2.0 1.2
0.2 1.3 0.01
0.4 0.02
0.0
0.3
0.4 2.5
.6
.1
.7
.2
.3
.1
.3
.9
.4
Source: Tepner, Hardy, and Chamberlin, 1961, Table IX, p. 137. Reprinted by permission of the
publisher.
The distribution of beryllium in rats, as in humans, is a function
of the physicochemical state of the metal. Soluble beryllium reaches the
skeleton rapidly, whereas colloidal beryllium is first transported to the
reticuloendothelial organs (Klemperer, Martin, and Liddy, 1952). Table
6.2 shows the distribution of both acidic and neutral beryllium salts fol-
lowing intravenous injection into albino rats. Colloidal beryllium that
was deposited in the liver was mobilized gradually and redistributed to
bone tissue or excreted (Table 6.3).
The skeleton, liver, and kidney are the organs in rats which accumu-
late and retain beryllium to a significant degree. Twenty-four hours fol-
lowing intramuscular injection into rats of 20 yCi of 7Be as BeCl2, 40%
of the dose was absorbed from the injection site (Crowley, Hamilton, and
Scott, 1949). The bone accumulated 29% of this absorbed amount and main-
tained this level to the 64th day. The liver and kidney initially con-
tained a comparable level, which decreased tenfold by the 64th day. These
organs which had the highest levels of beryllium are the target organs of
the toxicological action of stable beryllium when administered parenter-
ally in a soluble form. Cikrt and Bencko (1975) and Scott, Neuman, and
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106
TABLE 6.2. DISTRIBUTION OF INTRAVENOUSLY INJECTED BERYLLIUM
COMPOUNDS 24 HOURS FOLLOWING INJECTION IN RATSa
Bone plus
Material Injected marrow^ Liver Spleen Number
(%) (%) (%) of rats
7BeCl2, carrier-free, pH 2 43 (±6) 4 (±0.4) 0.1 (±0.1) 10
7BeCl2 plus 0.15 micromole
of 9BeCl2, pH 2 53 (±8) 3 (±0.5) 0.05 (±0.05) 2
7BeCl2 plus 1 micromole
of 9BeCl2, pH 2 37 (±2) 25 (±3) 1 (±0) 2
7BeCl2, carrier-free, pH 6 17 (±4) 59 (±5) 1.7 (±0.7) 9
7BeCl2 plus 1 micronole
of 9BeCl2, pH 6° 13 (±0) 44 (±1) 6 (±2) 2
7BeCl2 plus 0.15 micromole
of 9BeCl2, plus 3 micro-
moles of citrate, pH 6 50 (±6) 2 (±1) 0.15 (±0.05) 2
7Be(OH)2 plus 0.3 micro- ,
mole of 9Be(OH)2d 15° (±3) 61 (±8) 8 (±3) 5
The values represent the average percent of the total recovered
radioactivity per organ. Figures in parentheses refer to the average
deviation.
Femoral marrow, counted separately, had minimal activity except
following the injection of Be(OH)2. In this case the activity corre-
sponded to 7% per gram of tissue.
CThe acid solution was neutralized and injected immediately before
any visible precipitation occurred.
Precipitated with NH3, coagulated by heating, washed by high-speed
centrifugation, and suspended in saline.
Source: Adapted from Klemperer, Martin, and Liddy, 1952, Table I,
p. 150. Reprinted by permission of the publisher.
Allen (1950) also found that the skeleton, liver, kidneys, and spleen of
both rats and rabbits contained the highest amounts of beryllium (7Be as
7BeCla or 7BeSO<,) administered intravenously. Rat liver and kidneys con-
tained 23.6% and 1.6%, respectively, of a given dose at 0.025 mg of beryl-
lium per kilogram of body weight; and 32.3% and 1.3%, respectively, of a
dose at 0.25 mg of beryllium per kilogram of body weight (Cikrt and Bencko,
1975). The distribution of 7Be differs when it is administered intrave-
nously as the isotope alone or with a carrier (Scott, Neuman, and Allen,
1950). The beryllium administered as the isotope alone is taken up rapidly
in the bone, because the small amount of beryllium present is soluble in
the body fluids. However, when administration is with the isotope plus
carrier, some of the beryllium is insoluble and is excreted to a greater
extent than the soluble beryllium.
-------
TABLE 6.3. REDISTRIBUTION AND EXCRETION OF BERYLLIUM IN RATS
State of 7Be
Carrier-free,
7Be(OH)2 + 3
9Be(OH)2
Carrier-free,
Bone plus marrow (%)
injected
pH 2
micromoles
pH 6
1
day
46
15
12
21
days
48
28
22fc
Difference
+2
+13
+12
1
day
4
61
66
Liver (%)
21
days
0.4
23
36b
Difference
-3.6
-38
-30
1
day
39
8
17
Excretion (%)
21
days
49
31
35fo
Difference
+11
+23
+18
Number of rats
1
day
4
5
4
21
days
4
5
3fc
Animals sacrificed after seven days.
Femoral marrow, counted separately, had minimal activity except following the injection of Be(OH)2. In this case
the activity corresponded to 7% per gram of tissue.
Source: Adapted from Klemperer, Martin, and Liddy, 1952, Table II, p. 151. Reprinted by permission of the
publisher.
-------
108
Furchner, Richmond, and London (1973) reported that only the bone
and muscle of rats contained significant levels of beryllium 71 days after
intraperitoneal injection. These tissues retained more than 1% of the
dose (7BeCl2) (Table 6.4). Rats and mice were also given 7BeCl2 by intra-
venous injection and oral administration. More 7Be was retained from
intravenous than from intraperitoneal injection, and almost no 7Be was
retained from oral administration.
Reeves (1965) fed beryllium sulfate in drinking water to Sprague-
Dawley male rats for up to 24 weeks. Most of the beryllium was unabsorbed
in the gastrointestinal tract. Distribution levels were, therefore, high-
est in the gastrointestinal tract and contents; levels in the skeleton
were also high, followed by levels in the blood and liver (Table 6.5).
On the average, 80% of the ingested beryllium was recovered, primarily in
the feces.
Rats exposed by inhalation to BeSOi, aerosol (34.25 yg of beryllium
per cubic meter, a concentration that produces lung cancer in 100% of the
animals) showed decreasing accumulation rates in the lungs and tracheo-
bronchial lymph nodes during continuous exposure (Reeves and Vorwald, 1967).
Pulmonary beryllium levels increased until 36 weeks of exposure, when the
concentration plateaued, possibly because equilibrium was established
between deposition and clearance (Figure 6.1). Males accumulated higher
beryllium levels than females because of their larger size. Lymph node
levels of beryllium peaked concurrently with the plateau of pulmonary
beryllium levels and then decreased after the 52nd week (Figure 6.2).
Females had lower beryllium levels in lymph nodes because of less effi-
cient utilization of this clearance route. The metal was systemically
distributed from the nodes and possibly incorporated into the nuclei of
certain pulmonary cells. Beryllium incorporation into the cell nuclei
may be involved in the development of pulmonary carcinogenesis in rats.
Intravenously injected 7BeSOi, also has an affinity for cell nuclei
in rats (Witschi and Aldridge, 1968). For in vivo studies, 63% of the
dose (83 micromoles of 7Be as 7BeSOi, per kilogram of body weight) was
found in the nuclear fraction of the liver which, however, also contained
cell debris. Beryllium was also taken up by lysosomes. Table 6.6 shows
that as the beryllium dose injected into rats increased to toxic levels,
the amount of beryllium in the nuclear fraction of the liver homogenate
increased. This increase in concentration does not appear in the other
homogenate fractions. Kharlamova and Potapova (1968) also showed that
beryllium was distributed in all cellular fractions but was mainly con-
centrated in the nuclei.
6.2.2.2.2 Blood levels — Data concerning blood beryllium concentrations
are available only for experimental animals. Beryllium levels in rat blood
decrease with time following administration. At 0.25 day after intraperi-
toneal injection, the blood contained 0.47% of the dose and 0.82% of the
body burden; at 71 days, 0.044% of the dose and 0.26% of the body burden
was retained in the blood (Furchner, Richmond, and London, 1973). Follow-
ing intravenous administration of 7BeCl2, rat blood levels of the metal
also decreased rapidly with time (Cikrt and Bencko, 1975). A dispropor-
tionately high beryllium level of 4.47% (2.2 yg of Be2+ per milliliter of
-------
TABLE 6.4. DISTRIBUTION OF 7Be IN RATS AFTER INTRAPERITONEAL INJECTION
Tissue
Whole body
Carcass
Pelt
Liver
Gut
Remains
Kidney
Spleen
Lung
Testis
Bone
Muscle
Effective retention
0.25 day
5 7. 04- 100. Oa
(386)k
40.26-70.58
(225)
2.09-3.66
(74.8)
4.38-7.68
(13.9)
3.84-6.73
(32.1)
1.17-2.05
(19.4)
3.54-6.21
(2.94)
0.16-0.28
(0.85)
0.26-0.46
(2.53)
0.07-0.12
(3.72)
34.72-60.87
(26.26)
5.03-8.82
(189)
1 day
55.86-100.0
(362)
42.11-75.38
(211)
1.70-3.04
(73.4)
4.40-7.88
(13.2)
3.10-5.55
(24.5)
1.13-2.02
(21.3)
3.18-5.69
(2.63)
0.17-0.30
(0.89)
0.17-0.30
(2.28)
0.08-0.14
(3.68)
36.0-164.46
(25.66)
3.31-5.92
(186)
3 days
52.47-100.0
(327)
41.45-79.00
(210)
1.40-2.67
(67.2)
4.16-7.93
(12.3)
2.44-4.65
(26.2)
0.96-1.83
(17.5)
1.62-3.09"
(2.58)
0.18-0.34
(0.82)
0.28-0.53
(3.47)
0.08-0.15
(3.71)
36.62-69.79
(26.61)
3.38-6.44
(184)
6 days
46.83-100.0
(366)
39.32-80.85
(213)
0.98-2.02
(70.5)
2.49-5.12
(13.4)
1.57-3.32
(28.6)
0.75-1.54
(20.3)
0.85-1.75
(2.88)
0.17-0.35
(0.90)
0.14-0.29
(2.72)
0.05-0.10
(3.60)
34.63-71.21
(24.29)
3.77-7.75
(188)
10 days
44.83-100.0
(390)
38.89-87.79
(229)
0.73-1.65
, (70.5)
1.30-2.93
(15.0)
1.13-2.55
(31.5)
0.64-1.44
(24.4)
0.51-1.15
(2.89)
0.13-0.29
(0.79)
0.10-0.23
(2.22)
0.05-0.11
(3.79)
36.00-81.26
(26.45)
2.32-5.24
(203)
30 days
30.17-100.0
(380)
28.65-94.96
(225)
0.31-1.03
(68.6)
0.31-1.03
(13.9)
0.39-1.29
(29.4)
0.24-0.80
(22.7)
0.12-0.40
(3.00)
0.18-0.60
(0.85)
0.082-0.27
(2.70)
0.041-0.14
(4.01)
25.93-85.95
(27.57)
2.01-6.66
(198)
71 days
16.86-100.0
(394)
16.49-97.80
(236)
0.16-0.95
(71.4)
0.12-0.71
(13.9)
0.13-0.77
(30.5)
0.17-1.01
(20.5)
0.10-0.59
(3.19)
0.12-0.71
(0.93)
0.092-0.54
(3.06)
0.12-0.71
(4.06)
15.65-92.82
(27.64)
6.64-9.73
(208)
b,
The first value is percent of injected dose, and the second is percent of body burden.
Wet tissue weight (in grams).
Source: Adapted from Furchner, Richmond, and London, 1973, Table 3, p. 297. Reprinted by permission of
the publisher.
-------
TABLE 6.5. TISSUE DISTRIBUTION AND BALANCE OF BERYLLIUM IN RATS FED BeSO^ IN DRINKING WATER
Beryllium source
and
tissues analyzed
Consumption
Spillage
Total intake
Heart
Lungs
Kidneys
Spleen
Gastrointestinal
tract
Skeleton
Bloodfo
Liverfc
Total body0
Body + output
Percent ,
recovery
0.16 pg of Be2+ per liter of drinking water
No. 1
(6 weeks)
157. 90a
4.10
153.80
0.01
0.01
0.01
0.01
2.00
1.08
• 0.00
0.20
3.32
78
No. 2
(12 weeks)
446.00
20.00
426.00
0.01
0.00
0.01
0.00
3.00
1.24
0.16
4.42
324.02
76
No. 3
(18 weeks)
639.50
13.00
626.00
0.00
0.00
0.00
0.00
3.60
2.86
0.15
0.00
6.61
536.81
86
No. 4
(24 weeks)
862.90
9.70
853.20
0.01
0.00
0.01
0.00
3.10
0.77
0.16
0.07
4.12
744.92
87
1.66 yg of Be2+ per liter of drinking water
No. 1
(6 weeks)
2069.60
125.00
1944.60
0.01
0.04
0.10
0.01
0.73
0.15
0.01
1.05
1163.85
60
No. 2
(12 weeks)
3891.10
26.00
3865.10
0.01
0.01
0.00
0.01
14.00
1.94
0.27
0.02
16.26
3199.86
83
No. 3
(18 weeks)
5830.80
18.00
5812.80
0.00
0.02
0.01
0.00
12.00
0.95
0.14
0.16
13.28
5297.48
91
No. 4
(24 weeks)
10,344.60
180.00
10.164.60
0.00
0.01
0.01
0.00
21.00
1.12
0.14
0.04
22.32
7407.12
73
Micrograms.
Froln aliquot.
Q
Sum of organs analyzed.
Body + output x 100 per intake.
Source: Adapted from Reeves, 1965, Table 2, p. 212.
Reprinted by permission of the publisher.
-------
Ill
ORNL-DWG 77-4593A
20
15
o
I
CD
10
5 -
INDIVIDUAL ANIMALS
AND MEAN TREND
• MALES
o— FEMALES
n
4
,/T. 1 • 1 I I!''1:!
12 20 28 36 44 52 60
AGE (weeks)
< FYDnciiDr ,.— —
1 1 !
68 76
»-
': \
84
Figure 6.1. Pulmonary beryllium levels during and after BeS04
exposure in rats. Source: Adapted from Reeves and Vorwald, 1967,
Chart 1, p. 447. Reprinted by permission of the publisher.
0.20
o —
O
tr
OQ to
O LU
LU Q
I O
5 0.15
0.10
0.5
0)
CO
O
INDIVIDUAL ANIMALS
AND MEAN TREND
• MALES
_ o FEMALES
ORNL-DWG 77-4596A
12 20 28
36 44 52
AGE (weeks)
•EXPOSU R E-
60 68 76! 84
Figure 6.2. Tracheobronchial lymph node beryllium levels during
and after BeSOA exposure in rats. Source: Adapted from Reeves and
Vorwald, 1967, Chart 2, p. 448. Reprinted by permission of the
publisher.
blood) of a dose of 0.25 mg of Be per kilogram of body weight was found
5 hr after injection, compared with 0.02% (0.0013 yg of Be2+ per milli-
liter of blood) of a 0.025-mg/kg dose. The differences, however, became
balanced with respect to dose 24 hr following injection and at 48 hr. The
rapid and great decrease between 5 and 24 hr corresponded to an increase
in beryllium content in the liver. One day after intramuscular injection
of carrier-free 7Be into rats, blood beryllium concentrations reached 1.99%
of the dose (Crowley, Hamilton, and Scott, 1949). Again, beryllium levels
decreased with time until at 64 days following administration the concen-
tration was 0.24% of the dose.
-------
112
TABLE 6.6. BERYLLIUM (7BeSOi4) IN SUBCELLULAR FRACTIONS FROM RAT LIVER
AFTER VARIOUS DOSES INJECTED INTRAVENOUSLY
Dose of BeSOi,
(micromoles /kg)
0.083
0.83
1.8
8.3
28
83
110
Nuclear
44
141
98
98
280
340
410
Specific activity** of
Heavy
mitochondrial
110
98
200
175
beryllium (% of
Light
mitochondrial
260
295
315
310
204
that of homogenate)
Microsomal Supernatant
70
93
57
63
160
125
35
20
Specific activity expressed as nanomoles of beryllium per milligram of protein.
Source: Adapted from Witschi and Aldridge, 1968, Table 5, p. 814. Reprinted by permis-
sion of the publisher.
Disappearance of beryllium from rat blood is influenced by the size
of the dose. Beryllium in the 10~9 g range, injected intravenously, dis-
appeared more slowly from circulation than carrier-free 7Be (in 10"18 g
range) (Vacher and Stoner, 1968a). Beryllium removal from blood was
biphasic, with the second phase having an inverse relationship between
dose and removal rate.
The difference between the clearance rate from blood of carrier-free
beryllium and beryllium plus carrier is demonstrated in Figure 6.3 (Scott,
Neuman, and Allen, 1950). Eighty percent of the carrier-free beryllium
dose injected intravenously into rabbits was removed within 7 min; after
2 hr the concentration in the blood remained constant. The disapperance
of beryllium plus carrier was constant over the time period.
6.2.2.2.3 Placental transfer — No data were found concerning placental
transfer of beryllium.
6.2.3 Elimination
6.2.3.1 Biological Half-life - Data on the biological half-life of beryl-
lium are limited to experimental animals exposed by injection, inhalation,
intravenous injection, and intraperitoneal injection. Furchner, Richmond,
and London (1973) administered carrier-free 7Be as the chloride intraven-
ously, intraperitoneally, and orally to mice, rats, monkeys, and dogs.
The half times in days are shown in Table 6.7; the whole-body activity
following parenteral injection for all species consisted of three compon-
ents. By calculation the biological half-lives after intravenous injection
were 1210, 890, 1770, and 1270 days in mice, rats, monkeys, and dogs, respec-
tively. In an inhalation study using high-fired beryllium oxide, Sanders
and Cannon (1975) estimated a biological half-life for beryllium oxide in
rats of about six months.
-------
113
ORML-DWG 77-4618
0 50 100 150 200 250 30O 350 400
MINUTES AFTER INTRAVENOUS INJECTION OF 7Be
Figure 6.3. The blood clearance of 7Be injected with and without
a carrier in rabbits. Symbols indicate data from individual animals.
Source: Adapted from Scott, Neuman, and Allen, 1950, Figure 2, p. 295,
Reprinted by permission of the publisher.
6.2.3.2 Urinary Excretion — Urinary analysis for beryllium in humans has
been studied as a means of diagnosing beryllium disease. Urinary excre-
tion of beryllium indicates past exposure but is not necessarily associated
with the disease (Tepper, Hardy, and Chamberlin, 1961); conversely, the
disease may exist even though beryllium excretion is not detectable. The
excretion rate appears related to the solubility of the inhaled compound
(Browning, 1969).
Negative assays do not represent the absence of beryllium disease;
20 to 38 diseased patients had negative beryllium urinary assays (Stoeckle,
Hardy, and Weber, 1969). The beryllium levels in those patients with posi-
tive tests ranged from 0.01 to 1.0 ug of beryllium per liter of urine.
There was no correlation between urinary beryllium levels and time after
exposure (Figure 6.4). Lieben, Dattoli, and Vought (1966) analyzed the
-------
114
TABLE 6.7. EFFECTIVE RETENTION OF 7Be IN MICE, RATS,
MONKEYS, AND DOGS
Species
Half time (days)
Component 1
Component 2
Component 3
Oral
Mice
Rats
0.1
0.3
0.5
Monkeys
Dogs
Mice
Rats
Mice
Rats
Monkeys
Dogs
0.3
0.4
0.3
0.3
0.2
0.2
0.3
0.5
3.7
2.7
Intraperitoneal
6.3
8.5
Intravenous
8.2
6.9
21.7
9.7
51.6
51.1
51.7
50.9
52.4
51.8
Source: Adapted from Furchner, Richmond, and London,
1973, Table 2, p. 294. Reprinted by permission of the
publisher.
urinary beryllium content from beryllium refinery workers, beryllium manu-
facturing workers, and residents in the immediate neighborhood of a beryl-
lium refinery. As shown in Table 6.8, there was no correlation between
presence or concentration of urinary beryllium and length of exposure to
the metal. However, it should be noted that except for cases 40 and 41,
none of the residents of the immediate area had positive tests. The two
positive cases were persons drinking water from a well contaminated with
beryllium. Of the ten beryllium disease cases and suspected cases, only
one had a positive urine beryllium test.
Ingested soluble beryllium is only slightly absorbed through the
intestines; hence, urinary excretion is minimal. Rats given 6.6 or 66 yg
of beryllium per day (as BeSO*.) in drinking water excreted in the urine
less than 1% of the fecal excretion level (Reeves, 1965). Urinary excre-
tion peaked sharply at one or two days following administration, peaked
again during the third week, and finally declined to trace levels (Figure
6.5).
-------
115
ORNL-DWG 77 — 4595A
10
9
8
z .,
LU 7
d
S 6
M. Q
fc 5
o: .
§3
*J
z
o
^
|
1222222 = POSITIVE ASSAY.
I 1 = NEGATIVE ASSAY.
_
NUMBERS IN PARENTHESES =
PATIENTS
WITH POSITIVE TISSUE ASSAYS FROM LUNG
"
-
.
(i)
fy<
(!)
BIOPSY OR POSTMORTEM
(2) (2)
(1)
/.
'/
'/
/
7f
\
/
1,
'/
/
t
i,
3
f
/
'/
/
/
f
/
/
(2)
(t)
(I)
T.
t.
'i.
0-1 2-5 6-10 11-15 >I5
YEARS AFTER EXPOSURE
Figure 6.4. Occurrence of urinary beryllium excretion by years
from last exposure in 38 patients. Source: Stoeckle, Hardy, and Weber,
1969, Figure 8, p. 554.
In rats the route of beryllium administration determines the route
of excretion. Fecal excretion is the major route following oral dosing,
while urinary excretion is the major route after intramuscular and intra-
venous injection. Rats injected intramuscularly with carrier-free 7Be
(1 cc of isotonic solution with 1400 counts per second of 7Be per rat)
excreted 15.0%, 14.6%, 24.4%, and 44.0% of the dose in the urine at 1, 4,
16, and 64 days, respectively, after administration (Crowley, Hamilton,
and Scott, 1949). Scott, Neuman, and Allen (1950) reported that urinary
excretion of beryllium following intravenous injection in rats and rabbits
was the major excretory route. Rats given carrier-free 7Be (9.3 x 10"11
g per kilogram of body weight) excreted 38.8% of the dose during the first
24 hr, whereas those animals receiving 7Be plus a carrier, such as BeSO<,
(1.5 x 10~4 g of 7Be per kilogram of rat), excreted only 24.2% of the dose.
Rabbits likewise excreted more beryllium, 27.3% of the dose, during the
first 6 hr when given carrier-free Be than when given beryllium with the
carrier, for which they excreted only 12.2% of the dose. The difference
may result from a more rapid mobilization of beryllium from the liver,
spleen, and bone marrow and a slower mobilization from the bone, since the
bone was the only tissue with large amounts of beryllium when only the
isotope was injected.
Differences in excretory route following various means of adminis-
tration are further demonstrated in Table 6.9. In all species — mice,
rats, monkeys, and dogs — urinary beryllium excretion was the major route
following parenterally or intravenously administered beryllium (Furchner,
Richmond, and London, 1973). Later, the amount lost in the feces was about
equal to that lost in the urine. That which was excreted in the urine
following oral dosage is almost negligible.
-------
116
TABLE 6. 8. BERYLLIUM WORKERS AND NEIGHBORHOOD RESIDENTS
Case
number
1
2
3
&
5
6
7
g
9
10
11
12
13
14
15
16
17
20
21
22
23
24
25
26
27
28
29
30
31
32
33
34
35
36
37
38
3»
40
41
Type of work
Billet vorker
Furnace workers
Rolling department
Oxide department.
rolling mill
Oxide department
Alloy worker
Laboratory worker
Machine repair
Ventilating contractor
Sheet metal worker
Mold manufacture
Machine repair
Mold manufacture
Mold manufacture
8 y P
Neighborhood resident
Neighborhood resident
Neighborhood resident
Neighborhood
Neighborhood
Neighborhood
Neighborhood
Neighborhood
Neighborhood
Neighborhood
Neighborhood
Neighborhood
Neighborhood
Neighborhood
Neighborhood
Neighborhood
Neighborhood
Neighborhood
Neighborhood
esident
esident
esident
esident
esident
esident
esident
esident
esident
esident
esident
esident
esident
esident
esident
esident
Neighborhood resident
Neighborhood resident
Neighborhood resident
Length of exposure
7 years (1941-48)
9 years (1941-50)
7 years (1948-55)
3 months (1942)
5 months (1942)
6 months (1942)
4 months (1944)
1 year (1962)
Intermittently, 2 months
total (1955-56)
Intermittently, 2 months
total (1963)
1962
1962
For 1 year prior to
1962
For 10 years prior to 1962
prior to 1963
prior to 1963
Berylliosis
Yes
No
No
Yes
Yes
?
Yes
No
Dermatitis
Dermatitis
No
No
No
No
No
No
No
Yes
Yes
Yes
t
?
?
9
No
?
Dermatitis
Micrograms of
beryllium per Residence distance
liter of urine from plant (miles)
0.26
0.23 (6 months later)
0.07
Negative
Negative
Negative
Negative
Negative
Negative
Negative
Negative
0. 15S
0.052
Negative
0.0017
Negative
Negative
Negative
Negative
Nega t ive
Negative
Negative
Nega t i ve
Negative
Negative
Negative
Negative
Negative
Negative
Negative
Negative
Negative
Negative
Negative
Negative
Negative
Negative
Negative
Negative
Negative
Negative
Negative
Negative
0.019
0.057
1 1/2
1/2
5
3
1/4
A
1
1/4
5
1/2
1/4
1/4
1/4
1/4
1/4
1/4
1/4
1/4
1/4
1/4
1/4
1/4
Source: Adapted from Lieben, Dattoli, and Vought, 1966, Tables 1-5, pp.332-333. Reprinted by permission of the publisher.
Dose levels appear to influence the amount of beryllium excreted in
urine following intravenous injections into rats. These urinary beryl-
lium levels seem to correspond to beryllium blood plasma levels (Cikrt and
Bencko, 1975). A dose of 0.025 mg of Be2"1" per kilogram of body weight
produced a higher urine beryllium level (21.1% of dose) than did a dose
of 0.25 mg of Be2"1" per kilogram of body weight (4.2% of dose). However,
the higher dose gave the maximum excretion level after 5 to 24 hr. Dur-
ing this rise in renal excretion there was a corresponding decrease in
beryllium blood plasma levels.
6.2.3.3 Fecal Excretion — As previously mentioned, oral administration
of beryllium leads to greater excretion in feces than in urine. Sixty to
ninety percent of the total oral dose of 6.6 yg of beryllium per day and
of 66.6 yg of beryllium per day was found in the feces of rats (Reeves,
1965). The daily fecal beryllium excretion peaked during the first week
of exposure, decreased, and finally plateaued below the intake level dur-
ing the ninth week of exposure. Greater fecal beryllium excretion follow-
ing oral dosing also occurs in mice, monkeys, and dogs. Furchner, Richmond,
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117
ORNL-DWG 77-4411A
(a)
• INDIVIDUAL MEASUREMENTS
o AVERAGE FOR A GIVEN DAY
— STANDARDIZED CURVE OF DAILY EXCRETION
I i r i i
6 9 12 15 18
DIETARY ADMINISTRATION (weeks)
I
21
I
24
1.0
z 0.8
LU
I 0.6
LU
Q.
0.4
CM
0.2
+
CM
,2 0.10
0.05
(b)
• INDIVIDUAL MEASUREMENTS
0 AVERAGE FOR A GIVEN DAY
~ STANDARDIZED CURVE OF DAILY
EXCRETION
2 3 6 9 12 15 18 21
DIETARY ADMINISTRATION (weeks)
24
Figure 6.5. Urinary excretion of beryllium in male rats fed Be
in drinking water. (a) 0.16 mg of beryllium per liter of drinking water,
(2>) 1.66 mg of beryllium per liter of drinking water. Source: Adapted
from Reeves, Arch. Environ. Health, August, Vol. 11, Figures 5 and 6,
p. 211, Copyright 1965, American Medical Association. Reprinted by
permission of the publisher.
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118
TABLE 6.9. EXCRETION OF 7BE
Urinary/fecal ratio
apecies
Mice
Rats
Monkeys
Dogs
Mice
Rats
Monkeys
Dogs
Mice
Rats
1 day
0.0024
0.0008
0.0029
3.50
21.35
4.03
48.61
3.21
10.20
2 days 7 days
Oral
0.0021
0.0460
0.0035
Intravenous
0.51 0.96
1.00 1.51
0.52
4.62
Intraperitoneal
0.80 0.91
0.75 1.13
14 days
1.17
1.44
0.62
1.17
Chronic oral (56 days)
0.0044
a
Average urinary/fecal ratio during 56 days.
Source: Adapted from Furchner, Richmond, and London,
1973, Table 4, p. 298. Reprinted by permission of the
publisher.
and London (1973) reported that mice excreted 98% of the administered
dose during the first day, whereas urinary excretion, by comparison, was
only 0.24% of the dose. During the second day, rats, monkeys, and dogs
all excreted 100% of the dose.
By contrast, rats and rabbits excreted only 9.8% and 2.3%, respec-
tively, of intravenous injection of 7Be over a seven-day period (Scott,
Neuman, and Allen, 1950). Beryllium fecal excretion in rabbits increased
gradually, peaked on the fourth day, and then decreased. The addition of
a carrier, BeSO^,, to the isotope did not influence the amount excreted.
In rats, 7Be was excreted in greater quantities by those animals receiv-
ing the isotope plus carrier than by animals receiving only the isotope
(Table 6.10). Excretion in all rats was approximately equal on the first
day, with the differences in excretion taking place during the next six
days. Rats intravenously injected with two levels of 7BeCl2 excreted ap-
proximately the same amounts of 7Be in the feces (Cikrt and Bencko, 1975).
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119
TABLE 6.10. DAILY FECAL EXCRETION OF 7Be IN RABBITS AND RATS
(percent of administered dose)
1 day 2 days 3 days 4 days 5 days 6 days 7 days Total
Rabbits
Rats , isotope
plus carrier
Rats, isotope
only
0.1
4.2
3.5
0.3
1.6
0.8
0.3
2.0
0.4
0.5
1.2
0.3
0.3
1.1
0.2
0.3
1.0
0.2
0.2
0.7
0.2
2.0
11.8
5.6
Source: Adapted from Scott, Neuman, and Allen, 1950, Table III, p. 294. Reprinted by permis-
sion of the publisher.
Those animals dosed with 0.025 mg of Be2+ per kilogram of body weight
excreted 1.7%, 2.2%, and 1.6% of the dose at 5, 24, and 48 hr, respectively.
Rats given 0.25 mg of Be2+ per kilogram of body weight excreted 1.7%, 1.6%,
and 2.1% at 5, 24, and 48 hr, respectively. Intramuscular injection of
carrier-free 7Be produces slightly higher beryllium excretion levels in
rats: 4.25%, 4.17%, 9.25%, and 12.1% of the dose at 1, 4, 16, and 64 days,
respectively (Crowley, Hamilton, and Scott, 1949).
6.2.3.4 Biliary Excretion — Biliary excretion of intravenously injected
7Be and 7BeCl2 in rats represents only a small portion of total excreted
7Be. Rats given 0.025 mg of Be2+ per kilogram of body weight excreted
0.56% of the dose 5 hr after dosing and 0.27% of a dose of 0.25 mg of
Be2+ per kilogram of body weight (Cikrt and Bencko, 1975). Both of these
amounts are far below the levels excreted in the urine and contributed
only about 1/6 of the beryllium content of feces. The dose levels influ-
enced not only the total amount excreted but also the excretion rate (Fig-
ure 6.6). The highest bile excretion rate of 7Be from the lower dose
occurred between 1 and 4 hr after administration, whereas the peak excre-
tion rate from the higher dose occurred after the first 5 hr. The biliary
excretion rate of 7Be was related to the ability of beryllium to bind
itself on certain bile components. In respect to total body beryllium
excretion, bile plays only a minor role.
6.3 EFFECTS
Persons exposed to beryllium by inhalation can develop a respiratory
disease, which may be either acute or chronic. Dermatitis or ulcers can
result from direct skin contact. These exposure effects will be referred
to as acute or chronic beryllium disease. The term berylliosis will not
be used.
6.3.1 Potential Exposure Sources
Beryllium metal and its industrially used compounds are known to cause
disease (Roschin, 1971). Prior to 1950, many cases of beryllium disease
were associated with the manufacture and use of fluorescent lamps containing
beryllium phosphors. Use of these compounds was discontinued in 1949.
Since 1950 the increased use of beryllium in aerospace industries, gyro-
scopes i and nuclear reactors has resulted in increased exposures (Hasan
and Kazemi, 1973, pp. 1052-1053). The use of beryllium in U.S. industry
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120
ORNL-DWG 77-4591A
B
0.4
0.3
5s 0.2
0.1
«• °-3
O
xO.2
55 0.1
10
5
B
12345
TIME (hr)
(b)
Figure 6.6. 7Be bile excretion in rats after intravenous administra-
tion of 7BeCl2. Dose: (a) 0.025 mg of Be2+ per kilogram of body weight;
(£>) 0.25 mg of Bea+ per kilogram of body weight. A, cumulative 7Be excre-
tion; B, percentage of 7Be excreted per milligram of bile per minute; C,
percentage of 7Be excreted per minute; D, bile flow rate. Source: Adapted
from Cikrt and Bencko, 1975, Figures 1 and 2, pp. 54-55. Reprinted by
permission of the publisher.
continues to be widespread (Cralley, 1972) and is expected to increase
four- to sixfold by the year 2000 (Heindl, 1970, p. 498). Processes that
release beryllium into the air include melting, casting, sawing, grind-
ing, buffing, welding, cutting, electroplating, molding, ball milling,
drilling, machining, and packaging. Thus worker exposure in beryllium
industries can be widespread. Industries where beryllium is processed
and its compounds manufactured and handled include mining and benefici-
ation of beryllium minerals, extraction of beryllium, alloy manufactur-
ing, metallurgical operations, phosphor manufacturing, beryllium ceramic
products, electronic equipment manufacturing, nonferrous foundry products,
aerospace equipment specialty products, tool and die manufacturing, chem-
icals, and beryllium alloy machining and fabrication. Beryl ore has not
caused detectable illness in humans (Hamilton and Hardy, 1974).
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121
The chemical and metallurgical procedures used in beryllium process-
ing plants present exposure problems through inhalation and skin contact
(Donaldson, 1959). Proper equipment and ventilation must be used to re-
duce air beryllium concentrations to permissible levels. To help allevi-
ate exposure problems at a refining plant where beryl ore is taken down to
nuclear-grade beryllium metal, clean clothing is supplied daily to employ-
ees, exhaust ventilation systems keep air streams at optimum velocities
for accumulating dust particles, and air samples are routinely taken
(Epstein, 1959). In beryllium machining operations a high-vacuum-type
control system, high air velocity but low air capacity, reduces beryllium
concentrations in the air near the machines (Chamberlin, R. I., 1959).
Beryllium contamination of the work atmosphere in research operations can
result from using pure metal blocks in critical assemblies for nuclear
rocket engines and in preparation of beryllium targets for cyclotrons
(Hyatt et al., 1959).
Besides industrial exposure, persons may be exposed in other sur-
roundings. Beryllium may be found in alloys in the fabrication of prosth-
odontic appliances (Hinman et al., 1975). Because of this, employees of
dental laboratories may be exposed to high concentrations of beryllium,
23 yg/m3, when using a lathe without local lathe ventilation in operation.
Persons may be exposed to beryllium unknowingly from mantle-type camp
lanterns (Griggs, 1973). The mantle contains approximately 600 yg of beryl-
lium metal, which is volatilized and becomes airborne during the first 15
min of use of a new mantle. Such exposures may present an inhalation haz-
ard to users.
People living near beryllium-using plants are also exposed to the
metal. The chief neighborhood problems of beryllium pollution are associ-
ated with extractive processing, metal production, and alloy production
(Silverman, 1959). Through site selection of the plant, emission controls,
and proper stack height, the neighborhood beryllium air levels can be main-
tained below hazardous concentrations. Use of large beryllium-powered
rocket motors had been considered at one time; however, policy is against
the firing of these missiles within the continental United States, and
thus this is not a current source of exposure (Robinson, 1973).
Beryllium-level standards have been set forth for work areas and
neighborhoods surrounding beryllium-using plants. Workers may not be
exposed to a concentration of beryllium greater than 2 yg of total air-
borne particulate beryllium per cubic meter of air determined as a time-
weighted average exposure for an 8-hr work day, and no peak concentration
exceeding 25 yg of beryllium per cubic meter as determined by a minimum
sampling time of 30 min (U.S. Department of Health, Education, and Wel-
fare, 1972). In neighborhoods near plants, the average monthly concentra-
tion of beryllium should not exceed 0.01 yg of beryllium per cubic meter
(Cholak et al., 1962). At present, operators of plants have the option
of determining compliance either by measurement of ambient levels in the
vicinity of the plant or by emission testing. If the second option is
exercised, total emission into the atmosphere should not exceed 10 yg
Be/24 hr.
-------
122
Separate standards apply for rocket firing. Emissions to the atmos-
phere from that source shall not cause atmospheric concentrations of beryl-
lium to exceed 75 ug/m3 within 10 to 60 min, accumulated during any two
consecutive weeks, measured anywhere beyond the property line of such
source or at the nearest place of human habitation. If combustion prod-
ucts containing beryllium propellant are fired into a closed tank, emis-
sions from such tanks shall not exceed 2 g/hr at a maximum of 10 hr/day.
However, for beryllium oxide calcined in excess of 1600°C, a standard of
1.5 mg/min/m3 within 10 to 60 min is allowable.
6.3.2 Physiological Effects
6.3.2.1 Enzymes — Beryllium is a very potent enzyme inhibitor and is
active at concentrations as low as 10~6 M (Vorwald and Reeves, 1959).
Some affected enzymes are those which are altered in hosts having cancer
induced by nonberyllium agents. For example, nucleotidases, hyaluroni-
dase, and alkaline phosphatase activity, which are inhibited by beryllium,
are altered in cancer-bearing hosts. Along with enzyme inhibition, beryl-
lium also has an activating influence on ATPase and succinoxidase.
Thomas and Aldridge (1966) studied the action of beryllium on several
enzymes; the results are summarized in Table 6.11. Of the phosphatases
tested, only alkaline phosphatase was inhibited at concentrations of 1 \iM
or less, and only phosphoglucomutase of the phosphotransferases tested was
inhibited. With phosphoglucomutase the inhibitory process was competitive
but progressive with respect to magnesium; when the inhibition was estab-
lished it was no longer reversed by adding magnesium sulfate.
The inhibition of phosphoglucomutase occurs only in the presence of
a complex-forming agent such as cysteine or imidazole (Aldridge, 1966;
Aldridge and Thomas, 1966). The rate of the inhibition follows first-
order kinetics. Magnesium and beryllium compete with each other in direct-
ing the enzyme activity. In the presence of chelators, together with Mg2+,
1 g-atom of beryllium is bound per mole of rabbit muscle phosphoglucomu-
tase (Hashimoto et al., 1967). Beryllium binding prevents phosphoryla-
tion of dephosphoenzyme and dephosphorylation of phosphoenzyme. Beryllium
also inhibits phosphoglucomutases from shark and flounder muscle and rab-
bit liver. Beryllium blocks the tricarboxylic cycle by inhibiting the
activity of the dehydrogenases of ketoglutaric, malic, and succinic acid
(Mukhina, 1967).
In beryllium-induced midzonal liver necrosis, elevation of liver-
free acid phosphatase occurred 8 hr after injection of 0.8 mg of beryllium
per kilogram of body weight (as 7BeS04) into rats (Clary and Groth, 1973).
Elevation of serum enzymes isocitric dehydrogenase, glutamic-oxaloacetic
transaminase, and glutamic-pyruvic transaminase took place 48 hr after
injection; the level of lactic dehydrogenase was not elevated.
The induction of certain drug-metabolizing enzymes in rat liver,
including tryptophan pyrrolase, acetanilide hydroxylase, and aminopyrine
detnethylase are inhibited by beryllium (Witschi and Marchand, 1971). Activ-
ity of deoxythymidine kinase (Mainigi and Bresnick. 1969) and DNA polymer-
ase, thymidine kinase, and thymidylate kinase was also inhibited (Witschi,
1970, 1971).
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123
TABLE 6. 11. EFFECT OF BERYLLIUM ON VARIOUS ENZYMES
(Beryllium sulfate was used, and in each case the enzyme was preincubated with
beryllium for at least 10 min in the absence of substrate. At pH above 7,
precipitates were obtained with concentrations of BeSOi, of 1 mM and above.
Inhibition at these concentrations may be nonspecific.)
Enzyme
Alkaline phosphatase (kidney)
Acid phosphatase
Phosphoprotein phosphatase
Adenosine triphosphatase
(liver nuclei)
Adenosine triphosphatase
(liver mitochondria)
Adenosine triphosphatase
(brain microsomes)
Glucose 6-phosphatase
Polysaccharide phosphorylase
Phosphoglucomutase
Hexokinase
Phosphoglyceromutase
Ribonuclease
A-esterase (rabbit serum)
Cholinesterase (horse serum)
Chymotrypsin
Activated pH of
by Mg2"1" assay
+ 9.4
5.0
6.0
+ 6.8
+ 6.8
+ 7.4
6.5
6.0
+ 7.5
+ 7.4
7.0
7.5
7.6
7.6
7.0
Effect of BeSOi, at the
concentration indicated
50% inhibition, 1 \iM
No inhibition, 0.6 mM
No inhibition, 0.1 mM
No inhibition, 0.5 mM;
97% inhibition, 5 mM
No inhibition, 0.2 mM;
40% inhibition, 2 mM
20% inhibition, 0.64 mM
No inhibition, 0.8 mM
No inhibition, 0.64 mM;
91% inhibition, 6.4 mM
50% inhibition, 5 VM
45% inhibition, 1.5 mM;
no inhibition, 0.15 mM
No inhibition, 2.0 mM;a ,
15% inhibition, 1.0 m/T
No inhibition, 1.0 mM
No inhibition, 1.0 roM
No inhibition, 1.0 mM
10% inhibition, 1.0 mM
134 mM 3-phosphoglyceric acid as substrate.
20 mM 2-phosphoglyeerie acid as substrate.
Source: Adapted from Thomas and Aldridge, 1966,
sion of the publisher.
Table 1, p. 96. Reprinted by permis-
Sodium- and potassium-activated adenosinetriphosphatase is inhibited
by beryllium in the presence of Mg2"1" or Mn2+ (Toda, 1968; Toda, Koide, and
Yoshitoshi, 1971). Fifty percent inhibition was reached at a beryllium
level of 1.8 x 10~6 M, as shown in Figure 6.7. In the presence of Mg2 ,
K+ stimulated the rate of inhibition; NrU+ and Rb+ also stimulated enzyme
inhibition. Rat lung aryl hydrocarbon hydroxylase was inhibited by 150
micromoles/kg of BeSO* within the first two days following intratracheal
injection in rats (Jacques and Witschi, 1973). The pulmonary induction of
this enzyme by methylcholanthrene was not prevented by beryllium exposure.
Beryllium has a marked inhibitory action on alkaline phosphatase,
but serum alkaline phosphatase activity in rats remained unaffected by
inhalation exposure to beryllium sulfate (Reeves, 1974). In rabbits given
1% beryllium solutions intravenously or 25 mg of beryllium orally, alka-
line phosphatase activity (measured histochemically) was decreased in all
parenchymatous organs (Komitowski, 1972). Both BeSO* and BeCl2 inhibited
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124
100
ORNL-DWG 77-4592A
50
cr
>-
H
>
i—
o
2.5
5.0
7.5
10.0 20.0
BeCI2 CONCENTRATION IN PREINCUBATION
MEDIUM (X 10~6 M)
Figure 6.7. The inhibition of Na-K ATPase and BeCl2 concentration.
Source: Toda, 1968, Figure 2, p. 459. Reprinted by permission of the
publisher.
kidney and blood serum alkaline phosphatase from mice; in rats the renal
alkaline phosphatase activity decreased, whereas the enzyme's activity in
blood serum increased (Arkhipova and Demokidova, 1967). A relation exists
between total beryllium concentration and the amount of enzyme inhibition
(Bamberger, Botbol, and Cabrini, 1968). Below 10~7 M, beryllium produced
no inhibition when added to media containing the enzyme. Maximum inhibi-
tion occurred at 10~ M.
In addition to enzyme inhibition, beryllium also increases the activ-
ity of certain enzymes. Following intravenous injection of 12.5 to 1000 ug
of beryllium per kilogram of body weight into mice, there was an increase
in plasma 3-glucuronidase activity (Vacher, Deraedt, and Flahaut, 1975).
Beryllium levels above 200 yg produced a biphasic variation of g-glucuroni-
dase activity which peaked 7 and 96 hr following administration. Doses
below 100 to 200 yg produced a peak of activity only at 7 hr. The peak
at 96 hr was accompanied by an increase in transaminase activities. The
first activity phase was attributed to selective exocytosis of lysosomal
enzymes, while the second phase was attributed to toxic cell damage.
6.3.2.2 Nucleic Acids — Beryllium intratracheally injected into rats as
beryllium oxide (10.8 mg of beryllium total) altered cell RNA distribu-
tion (Vorwald and Reeves, 1959). Microsomal RNA dropped from 40% to 22%
of the total value, while there was a comparable rise in the RNA content
of the soluble supernatant cell fraction. Chevremont and Firket (1951)
showed that beryllium sulfate at a concentration of 10~3 M inhibited cell
division in the metaphase, with marked decrease in the intensity of the
Feulgen reaction for DNA. This was interpreted as blockade of DNA bio-
synthesis (Bassleer, 1965). The effect was specific to DNA, with RNA
biosynthesis remaining unaffected (Witschi, 1968). Modes of interaction
of the beryllium ion with DNA of various species were studied by Truhaut,
-------
125
Festy, and LeTalaer (1968) who noted preferential accumulation of radio-
beryllium in the nuclei of regenerating rat liver and an increase of the
sedimentation constant of DNA after contact with beryllium sulfate. Need-
ham (1974) found depression of the typical absorbance bands of DNA in the
presence of Be2+. Truhaut, Festy, and LeTalaer (1968) found inhibition
of DNase (50% at a concentration of 10~4 M) by beryllium and postulated
the formation of a DNA-beryllium complex. Vegni-Talluri and Guiggiani
(1967) expressed the opinion that beryllium exerted its effect on nuclear
activity by competing with magnesium in the activation of DNA polymerase;
however, Witschi (1970) showed that while beryllium did inhibit the repli-
cation of DNA in regenerating rat livers, it did not become attached to
DNA, and DNA cell content was not changed. Beryllium did not affect RNA
synthesis in early regenerating rat livers (Marcotte and Witschi, 1972).
The incorporation of 1£*C-orotic acid into total cellular RNA, a procedure
to measure RNA synthesis, was not affected by beryllium. Beryllium in
various physical forms can suppress DNA synthesis (Jones and Amos, 1975).
The response of normal lymphocytes from beryllium-allergized guinea pigs
to phytohemagglutinin was inhibited by beryllium sulfosalicylate. Witschi
(1968) also reported inhibition of DNA synthesis; this inhibition was
caused by depression of the incorporation of thymidine into DNA. There
is increasing evidence that beryllium can present interference with nucleic
acid function at the transcriptional level. Misincorporation of polydeoxy-
adenosylthymidine by micrococcal DNA polymerase in the presence of beryl-
lium, with strong inhibition of 3'-5' exonuclease ("editing") activity of
the enzyme, was recently noted by Luke, Hamilton, and Hollocher (1975),
and beryllium alone, among several divalent cations, substantially affected
the fidelity of in vitro DNA transcription by single base substitutions
(Sirover and Loeb, 1976).
Needham (1974) has agreed that the target for beryllium toxicity is
the cellular DNA and that inhibition of cell proliferation, regeneration
and development, teratogenesis, and anemia are effects resulting from
beryllium inhibition of DNA replication and transcription. He presents
data showing a strong affinity of Be2+ for DNA in vitro and cites other
work that supports this point of view.
6.3.2.3 Proteins — Beryllium compounds react selectively only with cer-
tain proteins (Reiner, 1971). Beryllium affects the cellular distribution
of protein in rats given 33 mg of beryllium (in three equal doses) by in-
tratracheal injection (Vorwald and Reeves, 1959). The protein in micro-
somes of cells from lung tissue almost doubled when compared with that of
control animals. No change occurred in the protein content of the nuclei
or mitochondria, however. Cytoplasmic protein appeared to change from a
soluble to an insoluble form. Changes in the protein-carbohydrate com-
ponents of pulmonary connective tissue from beryllium-exposed rats were
expressed as a rise in the oxyproline levels of pulmonary tissue (Ivanova,
1970). Total hexosamine content also increased; the greatest increase of
these components occurred during the first month following exposure to
beryllium. Pavlova, Kharlamova, and Kurysheva (1970) studied protein
metabolism during experimental berylliosis in rats and found an increase
in reactive sulfhydryl groups and in the rate of incorporation of lysine-
1-C1* into the soluble hepatic proteins. This was viewed as an increase
in the rate of protein biosynthesis (Kurysheva, 1969).
-------
126
Intravenous injection of beryllium into rats produces the appearance
in the serum of an immunologically specific protein referred to as a-macro-
feto protein (Vacher, Deraedt, and Benzoni, 1974). Production of this
protein was initiated by phagocytosis of the insoluble phosphate fraction
formed following beryllium introduction into rats. At 24 hr after intra-
venous injection of 0.75 mg of beryllium per kilogram of body weight, a
decrease in capacity to incorporate amino acids into liver protein occurred
(Witschi and Aldridge, 1967).
6.3.2.4 Immunologic Reactions — Sterner and Eisenbud (1951) suggested
that the epidemiology of berylliosis cases could involve an immunological
factor. Curtis (1951) concurrently developed a patch test. The patch
test itself appeared to be sensitizing and was believed to be responsible
for both dermal and pulmonary exacerbations of beryllium disease. It was
concurrently not used much as a diagnostic tool (Curtis, 1951; Niembller,
1962; Zschunke and Folesky, 1969). However, the phenomenon did indicate
that beryllium was antigenic. A search for humoral antibodies was made
(Voisin et al., 1964; Pugliese et al., 1968; Resnick, Roche, and Morgan,
1970; Resnick and Morgan, 1971) but it now seems well established that
beryllium hypersensitivity is essentially cell-mediated (Alekseeva, 1965;
Cirla, Barbiano di Belgiojoso, and Chiappino, 1968). Passive transfer
of hypersensitivity was accomplished in guinea pigs with lymphoid cells
while the transfer of serum was ineffective. Chiappino, Barbiano di
Belgiojoso, and Cirla (1968) and Chiappino, Cirla, and Vigliani (1969)
were also able to inhibit all cutaneous reactions to beryllium in guinea
pigs by injection of an antilymphocyte serum from rabbits; Turk and Polak
(1969) could suppress reactivity by intravenous injection of beryllium
lactate. Inhalation exposure to beryllium sulfate could also suppress
cutaneous reactivity (Reeves, Krivanek, and Palazzolo, 1975). Among
guinea pigs, not all individuals responded identically to the beryllium
challenge; ability to become sensitized was genetically controlled and
transmitted as a nonsex-linked, dominant trait (Polak, Barnes, and Turk,
1968).
Mode of administration and choice of beryllium compound also influ-
enced the nature of the immunological reaction. Vacher (1972) found only
those forms and routes which were capable of producing a complex with
skin constituents as immunogenic; freely diffusible forms were "tolero-
genic," including a very low dose of beryllium (4.78 ug/kg) intraperi-
toneally, or a high toxic dose (400 yg/kg) intravenously. Krivanek and
Reeves (1972) showed that the beryllium ion acts as a hapten in provok-
ing the immunological reaction. Complexes where the beryllium ion was
unavailable (aurintricarboxylate, citrate) could not elicit sensitivity,
whereas beryllium-serum-albuminate could elicit stronger sensitivity than
the beryllium ion alone (Table 6.12). Vasil'eva (1969, 1972) detected
beryllium-nucleoprotein complexes that were antigenic. However, evidence
was also presented that beryllium can interact with cells without prior
complexing to macromolecules and can inhibit the response of allergized
lymphocytes to antigen (Jones and Amos, 1974, 1975).
Measures of hypersensitivity, other than skin response, were recently
developed. Among these, lymphocyte blast transformation (Hanifin, Epstein,
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127
TABLE 6.12. SKIN RESPONSE TO ORAL ADMINISTRATION AND INTRADERMAL INJECTION
OF BeSOij, Be-ATA, Be-H CITRATE, AND Be-ALBUMINATE IN GUINEA PIGS
Compound
BeSOit
Be-ATA
Be-H citrate
Be-albuminate
Beryllium
concentration Group
1.0 yg Untreated
Beryllium orally
Beryllium injected
0.45 ug Untreated
Beryllium orally
Beryllium injected
0.45 ug Untreated
Beryllium orally
Beryllium injected
1.0 pg Untreated
Beryllium orally
Beryllium injected
Average reaction diameter
in millimeters at 24 hr
(±1 standard deviation)
2.5 ± 1.7
1.4 ± 1.7
4.1 ± 1.6
1.8 + 1.1
2.0 ± 1.2
2.5 ± 1.0
2.3 ± 1.4
2.0 ± 1.2
1.3 ± 1.0
3.6 ± 2.1
3.8 ± 2.3
5.7 ± 2.1
Source: Adapted from Krivanek and Reeves, 1972, Tables III, IV, V, and VI, pp. 49-50.
Reprinted by permission of the publisher.
and Cline, 1970) and macrophage migration inhibition (Henderson et al.,
1972) appear promising. They were applied both to human clinical material
(Jones-Williams, Grey, and Pioli, 1972; Deodhar, Barna, and Van Ordstrand,
1973) and to experimental guinea pigs (Marx and Burrell, 1973; Palazzolo
and Reeves, 1975).
The relation of cutaneous hypersensitivity to pulmonary berylliosis
is incompletely understood at present. There are reports on occasional
exacerbation or flareup of pulmonary berylliosis cases after patch test-
ing. There is also evidence that in guinea pigs dermal sensitivity and
pulmonary response to beryllium are in inverse relation (Reeves et al.,
1971, 1972). Maintenance of hypersensitivity through intracutaneous in-
jection modified and alleviated the pulmonary response after beryllium
inhalation (Reeves and Krivanek, 1974). The situation showed some simi-
larity to the relation between tuberculin sensitivity and tuberculosis,
where a controlled induction of sensitivity (e.g., with BCG vaccine) was
associated with increased resistance to tuberculosis. Perhaps the lymph-
ocytic and histiocytic response that followed the induction of cutaneous
hypersensitivity stimulated the phagocytosis of inhaled beryllium par-
ticles, or otherwise helped to destory the autoantigen formed in the
lungs.
6.3.2.5 Other Physiological Effects — Mitochondrial changes were pro-
duced in rats with experimental beryllium disease (Potapova and Seleznev,
1967). Both disintegration and swelling of the mitochondrial apparatus
occurred, with a loss of cristae. In pulmonary structures the basal mem-
branes of the alveolar septa became edematous and swollen, later becoming
-------
128
dense and thick. These changes corresponded to desquamation of cells
lining the alveoli and sclerosing of alveolar septa. Beryllium increases
plasma volume (Mosser and Clark, 1970). A single intravenous injection
of 6.67 micromoles of BeSOj, per kilogram of body weight in rabbits caused
a significant increase in the mean plasma volume. Increased globulin
levels and plasma volume occurred between 7 and 14 days following injec-
tion, whereas there was no effect on albumin levels or red cell mass.
Mean hematocrits decreased for 12 days and then rose toward normal.
Concentrations of beryllium as the sulfate from 0.0025 to 10 6 M
inhibited growth of chick embryo tissue cultures (Chevremont and Firket,
1951). Mitotic abnormalities occurred by prolonged contact with beryl-
lium ions. In some cells, metaphase was lengthened up to several hours.
These cells usually degenerated and became pycnotic or changed back into
elongated cells, with a resting nucleus reappearing. Thus anaphase and
telophase do not take place. Goldblatt, Lieberman, and Witschi (1973)
reported inhibition of mitosis in rat liver cells from partially hepa-
tectomized animals intravenously administered 15, 30, or 60 micromoles
of BeSOi, per kilogram of body weight treated 20 to 16 hr before death.
Changes also occurred in lysosomes 24 hr following beryllium injection:
they included vacuolization, loss of fibrils, and distortion of bile
canaliculi.
6.3.3 Acute Beryllium Disease
Acute beryllium disease is defined as including those beryllium-
induced disease patterns which last less than one year (Tepper, Hardy,
and Chamberlin, 1961). Patients develop acute inflammatory reactions at
the deposition site when challenged by toxic beryllium compounds in the
form of a mist, vapor, or dust (Vorwald, 1966). Severity of symptoms
seems dependent on the amount of exposure, toxicity and concentration of
the compound, and individual susceptibility (VanOrdstrand et al., 1945).
Acute chemical pneumonitis can be caused by inhalation of practically all
beryllium compounds (Love, 1972). Exposure to large concentrations of
soluble salts in beryllium processing plants has led to rapidly fatal
cases. Peyton and Worcester (1959) found that of those workers exposed
to beryllium, 6.4% to 10.8% developed acute beryllium disease. The U.S.
Beryllium Case Registry, up to 1972, reports 211 acute cases and 44 with
both acute and chronic beryllium disease (Hasan and Kazemi, 1973).
Acute beryllium disease is primarily a manifestation of direct upper
and/or lower respiratory tract irritation (Tepper, 1972a). Dermatitis,
skin ulcers, and conjunctivitis result from contact with soluble beryl-
lium salts (Vorwald, 1966; Higgins, 1968).
6.3.3.1 Dermatitis — Contact dermatitis from beryllium exposure is the
allergic type (Zielinski, 1959). Allergic dermatitis, expressed as intense
dermal erythema, occurs on exposed areas of the face, neck, sometimes arms
and hands, and develops within 6 to 15 days after initial exposure to sol-
uble compounds of beryllium, especially the fluoride. Lesions that form
on the trunk are usually a result of penetration of clothing or distribu-
tion to covered areas by contaminated hands (Tepper, Hardy, and Chamberlin,
-------
129
1961). Acute contact dermatitis is generally associated with fluoride or
sulfate salts of beryllium, and not with beryllium oxide powder (Browning,
1969). Dermatitis is generally regarded as a hypersensitizing reaction
instead of being due to a primary irritant. It is characterized by itch-
ing and reddened and elevated or fluid-accumulated lesions. In a study
of employees in a beryllium refining factory, 57.8% of those workers with
acute beryllium disease had contact dermatitis (Nishimura, 1966). Within
three months after employment, contact dermatitis occurred in 55% of those
who eventually got dermatitis. The cases were seen mostly in the extract-
ing and alloying process and in BeO manufacturing; they occurred most
frequently during the summer.
Several studies have examined beryllium-induced dermatitis using
guinea pigs as a model. Delayed hypersensitivity was expressed as a der-
mal reaction following intradermal injection of BeSO<, (Palazzolo and
Reeves, 1975). No reaction was produced by BeSOj, inhalation. The bind-
ing of beryllium to guinea pig epidermal constituents, such as alkaline
phosphatase and nucleic acids, was suggested by Belman (1969) as a pos-
sible mechanism for beryllium toxicity.
6.3.3.2 Beryllium Ulcer — The beryllium ulcer is caused by implantation
of a crystalline beryllium compound in skin abrasions. It starts as a
localized indurated papuloerythematous lesion which progresses to the
ulcer (Vorwald, 1966). The ulcer lasts until extrusion of the crystal
by surgical curettage of the ulcer base (Tepper, Hardy, and Chamberlin,
1961). Healing usually follows within two weeks. In a study of acute
beryllium disease in a beryllium refining plant, Nishimura (1966) found
an incidence rate of 5.7% for skin ulceration.
6.3.3.3 Conjunctivitis — Inflammation of the conjunctiva is usually
associated with contact dermatitis. The pathology ranges from a simple
congestion and hyperemia to cellular infiltration, and the condition can-
not be differentiated from inflammatory reactions due to other types of
irritants (Vorwald, 1966). Nishimura (1966) found a conjunctivitis fre-
quency of 20.9% among workers with the acute disease in the previously
discussed study. This was usually found in workers exposed to high con-
centrations of BeO.
6.3.3.4 Respiratory Tract Effects — Inhalation of toxic beryllium com-
pounds can induce inflammatory reactions of the respiratory tract tissues
between the nares and alveoli; upon intense exposure the inflammation may
extend into the lower tract (Tepper, Hardy, and Chamberlin, 1961). Soluble
acid salts have been responsible for the cases involving the upper respi-
ratory tract, whereas beryllium metal, oxide, and phosphor mixtures, as
well as acid salts, have produced pneumonitis. Acute pulmonary beryllium
disease may appear within a few weeks of initial exposure (VanOrdstrand,
1959). Acute beryllium disease is not necessarily easy to diagnose, since
some of the symptoms resemble those induced by other irritating chemicals.
Effects on the respiratory tract may take the form of nasopharyn-
gitis, tracheobronchitis, or acute chemical pneumonitis (Tepper, Hardy,
and Chamberlin, 1961). Nasopharyngitis has no specific clinical pattern
-------
130
and can be confused with the connnon cold. Symptoms are irritation of the
nose and pharynx with mild epistaxis, edematous and hyperemic mucous mem-
branes, and bleeding areas in the nose. Tracheobronchitis may be either
rapid or insidious in onset according to degree of exposure. A nonproduc-
tive spasmodic cough develops, with moderate exertional dyspnea and sub-
sternal discomfort, burning, or tightness. The upper respiratory tract
mucosa is usually hyperemic. Acute chemical pneumonitis may take either
of two forms: a fulminating illness after a brief massive exposure or an
insidious illness following prolonged exposure. Symptoms of pneumonitis
are development of a dry cough with substernal burning or aching, progres-
sive dyspnea, fatigue, anorexia, weight loss, cyanosis, moist pulmonary
rales, and slight temperature elevation.
Norris and Peard (1963) reported a case of acute chemical pneumonitis
in a worker in contact with beryllium-copper alloys. The onset of the
disease was rapid, with progression of dyspnea and evidence of systemic
disturbance. The percussion note was impaired over both upper zones ante-
riorly. Hazard (1959) reported on six cases that ended in death from pneu-
monitis of employees in a beryllium extraction plant. Usual symptoms such
as shortness of breath, chest pain, cough, and dyspnea were found; termi-
nal fever and cyanosis also occurred. Death, in each case, was attributed
to pulmonary embarrassment with or without acute cor pulmonale. The time
between exposure and disease onset was accurately determined for only one
case; this patient was exposed six days and four days prior to onset when
he removed his mask while cleaning a calcining furnace. No exposure con-
centrations were determined.
A study by Nishimura (1966) described in detail 192 cases of acute
beryllium disease that occurred between 1957 and 1964 in persons working
in a refining factory. Of these cases, 19 displayed acute upper respira-
tory tract disease, and 11 had acute pneumonitis. Of the upper respiratory
tract diseases 53% occurred during the first three months of employment.
This disease was found most often among those working in the extracting
and alloying processes. Symptoms were coughing, sore throat, and slight
general fatigue. Sixty-nine percent of these cases were cured within one
month, and none exceeded two months. Cases of acute beryllium pneumoni-
tis occurred between 32 and 90 days of employment and were associated with
extracting and alloying processes or manufacturing of BeO. The beryllium
concentrations to which the workers were subjected were 20 to 60 yg/m3.
These levels did not necessarily correlate with disease severity, clini-
cal findings, or length of illness. Table 6.13 summarizes the exposure
levels and the clinical progress of the pneumonitis in the 11 workers with
the disease. Table 6.14 summarizes the laboratory findings in these 11
patients.
Various studies have examined the effect of beryllium on the lungs
of experimental animals. Table 6.15 presents a summary of results from
exposing various animal species to beryllium by inhalation.
Various animal species show differing levels of susceptibility to
beryllium inhalation. Animals exposed to BeSO* at 47 mg/m3 displayed two
separate responses: (1) a highly acute phase in which the most suscepti-
ble species die and (2) a delayed phase in which little effect is shown
-------
131
TABLE 6.13. CLINICAL PROGRESS OF ACUTE BERYLLIUM PNEUMONITIS
n
0)
6
3
C
0)
00
CO
U
1
2
3
4
5
6
7
8
9
10
11
a
CO
CO
01
u
O
0> ki
00 p.
CO X-*
a 13
"OK 01
S CO X
CO 0) O
x £ "a.
v B
(/> W
m A
28
m A
21
m A
34
m B
34
m A
22
m A
34
m B
23
m A
26
m A
23
m A
23
m B
27
00
B C
O -H
•H a
U CO
CO 01 X
U K 0
4J CJ B
SOI 01
•O 3
o tr
§B 01
•H H
O ^*H
lJ ,^
•H CO
< 0 OJ
t-t i-l CO
oi a B
4J S O
B 0>
t-H
60
32
45
60
45
36
45
32
56
90
51
B
01 M
OI CO
OJ .-.
A -O OS
C X
rH CO CO
co ;a
u o>
0) a
s o
i-i
20
25
20
20
20
15
18
27
19
19
21
S
0 S
4_1 jj
g. u
CO O
C 01
•H fH
S Oi
Dry cough, +
dyspnea, general
malaise, fever
Dry cough,
dyspnea , fever ,
substernal pain
Dry cough, +
dyspnea, chest
pain, cyanosis
(needed oxygen
inhalating)
Dry cough, +
dyspnea, general
malaise,
sleeplessness
Dry cough,
dyspnea, general
malaise,
sleeplessness
Dry cough, +
dyspnea, fever,
cyanosis (needed
oxygen
inhalating)
Dry cough,
dyspnea"
Dry cough,
dyspnea, general
malaise, chest
pain
Throat pain, -
dry cough,"
dyspnea,"
headache
Dry cough,
dyspnea, substernal
tightness
Dry cough, +
dyspnea, subfebris
Beryllium
patch test
m
O 4-1 0) CO
C X CO
4-1 CO 4J CO Q)
K g 01 T3 C
CO X CO ^H
!-l 4J O B fH rH
01 CO *H O CO i-t
5D. 4-1
4J g 4J 0 UH
fn *£ CD H
CO
O
60
o
CXt
Complete
cure
Complete
cure
Complete
cure
Complete
cure
Complete
cure
Complete
cure
Complete
cure
Complete
cure
Complete
cure
Complete
cure
Complete
cure
A — extraction and alloying process, B — manufacturing of BeO.
Initial symptoms.
Source: Adapted from Nishimura, 1966, Table 6-a, p. 23.
at first but increasingly severe changes occur up to seven to ten weeks
of exposure (Stokinger et al., 1950). Figure 6.8 shows the variation in
species mortality as a result of beryllium sulfate exposure. Pulmonary
lesions produced in these species resemble those found in humans with acute
beryllium disease. Little change in the pulmonary responses occurred with
respect to changes in BeS04 concentrations ranging from 1 mg to 100 mg/m3.
A single intratracheal injection of a 1% zinc beryllium silicate solution
produced pulmonary lesions in guinea pigs which were comparable with those
produced by beryllium sulfate or oxide (Levy and Higgins, 1965).
-------
TABLE 6.14. LABORATORY FINDINGS OF ACUTE BERYLLIUM PNEUMOHITIS
Body weight
(kg)
01
1
z
1
2
3
4
5
6
7
8
9
10
11
Before
onset
58
51
56
50
53
55
46
49
51
58
56
id
01
D.
55
51
54
49
53
43
46
52
51
53
52
Pulmonary
function
t) 4J
O f U 01
C4 ~» ,Q U O U
" J g u oJ5*
76 15.200 1.800 46
29 12.400 1.700 42
54 8.500 1.000 25
40 8.600 1.400 39
14 6.200 2.000 49
31 6.800 1.100 28
15 7.200 1.300 48
32 4.900 1.900 47
31 6.100 2.000 51
13 7.200 2.500 61
38 9.700 2.900 72
Serum chemistry w
o
ii i
C /-s
iH i-l rH
-------
TABLE 6.15. EFFECTS ON VARIOUS ANIMAL SPECIES CAUSED BY EXPOSURE TO BERYLLIUM BY INHALATION
Substance
Animal
Concentration
or dose
Exposure
(duration)
Particle
size (tim)
Effects
Beryllium compounds
Beryllium
fluoride
Beryllium
oxide
5 cats, young
adult
6 cats, young
adult
14 dogs, young
adult
6 dogs, young
adult
6 dogs, young
adult; 3
rabbits
20 guinea pigs,
young adult
20 mice , young
adult
4 monkeys,
rhesus
10 rabbits,
young adult
120 rats, young
adult
40 rats, young
& old adult
6 dogs, beagle,
7.3-10.8 kg
65 rats
0.97 mg/m3 in
H20
10 mg/m3 in
H20
0.97 mg/m3 in
H20
10 mg/m3 in
H20
2.2(2.0-2.4)
rng/m3 in
H20
10 mg/m3 in
H20
10 mg/m3 in
H20
27 yg (5.2 yg
Be) /ft3 in
H20
0.97 mg/m3 in
H20
10 mg/m3 in
H20
0.97 mg/m3 in
H20
10 mg/m3 in
H20
120(40-300)
mg/m3
39.57 yg/liter
6 hr/day
(207 day)
6 hr/day
(3 wk)
6 hr/day
(207 day)
6 hr/day
(3 wk)
6 hr/day
(23 wk)
6 hr/day
(3 wk)
6 hr/day
(3 wk)
6 hr/day
(7-16 xday)
6 hr/day
(207 day)
6 hr/day
(3 wk)
6 hr/day
(207 day)
6 hr/day
(3 wk)
20 min
1-5 hr/day
(1-35 hr)
0.61(0.33-
0.94)
0.63(0.52-
0.74)
0.61(0.33-
0.94)
0.63(0.52-
0.74)
0.63(0.52-
0.74)
0.63(0.52-
0.74)
0.61(0.33-
0.94)
0.61(0.52-
0.74)
0.61(0.33-
0.94)
0.63(0.52-
0.74)
0.285(0.11-
1.25)
No deaths ; lung damage
No deaths
3 deaths; suspected ] Consolidation, emphysema,
macrocytic anemia 1 & slight edema in lungs;
1 death; 3 sacrificed f ?e 'ended to accumulate
moribund J *n l^s ' P"1™""?
lumph nodes, liver,
skeleton, & bone marrow
+ in RBC count & Hb levels; t in mean corpuscular volume
consistent with macrocytic anemia
7 deaths
6 deaths
2/4 deaths after 13-16 exposures from pneumonitis;
pulmonary emphysema, edema, granulomas (2/4), & fibrosis;
marked alveolar hyperplasia (4/4) & slight to moderate
metaplasia (4/4) of alveoli, & bronchial 4 bronchiolar
epithelium; marked lymph node hyperplasis (4/4) ; multiple
extraplumonary lesions
No deaths; suspected macrocytic anemia, lung damage
1 death; suspected macrocytic anemia; lung damage
73 deaths; minimal lung lesions
7 deaths; minimal lung lesions
4/6 Be-containing granulomas in lungs at 30 mo with no
excess collagen formation
Large amounts of dust (>24 mg Be/100 g) in lungs at >1 yr;
little tendency for Be to be redistributed from lungs
to other tissues; fibrous tissue proliferation from
35 day to >1 yr but no granulomatous inflammation in
lungs
(continued)
-------
TABLE 6.15 (continued)
Substance
Beryllium
oxide
Calcined
beryllium
oxide
Beryllium
phosphate
Beryllium
sulfate
Animal
2 cats; 10
dogs; 20
guinea pigs,
mixed English;
2 monkeys,
rhesus; 9
rabbits, New
Zealand; 90
rats, Wistar;
(all young
adults)
6 dogs, beagle;
5 monkeys,
cynamolgus
(all adults)
30 guinea pigs,
360-400 g
4 monkeys,
rhesus
4 cats, young
adult
5 cats, young
adult
12 dogs
Concentration
or dose
10 & 82 mg/m3 in
H20 (special
grade of BeO)
83 mg/m3 in
H20 (refrac-
tory grade
GC of BeO)
84-86 mg/m3 in
H20 (fluores-
cent grade of
BeO)
88 mg/m3 in
H20 (refrac-
tory grade SP
of BeO)
3.3-4.4 rag
Be/m3
2 mg in saline
66 ug (5.6 ug
Be)/ft3
0.95 mg (0.04 mg
Be)/m3 in H20
10 mg (0.43 mg
Be)/m3 in H20
47 mg (2 mg
Be)/m3 in H20
3.6-4.0 mg/m3 in
H20
Exposure Particle
(duration) size (um)
6 hr/day 0.47-0.59
5 day/wk
(15-40
day)
6 hr/day 1.13
5 day/wk
(60 day)
6 hr/day <1.0
5 day/wk
(10-17.5
day)
6 hr/day 0. 71
5 day/wk
(10 day)
3 x 30 min/
mo (2 yr)
Single i.t. 1-5
injection
6 hr/day
(30 day)
6 hr/day 0.25
(100 day)
6 hr/day 1.5
(95 day)
6 hr/day 0.96
(51 day)
6 hr/day
(2 mo)
Effects
*v
68% mortality in rats exposed
to 82 tng/m^ for 15 day;
all other treated animals
survived
All animals survived
5% mortality in rats exposed
to 87 mg/m3 for 10 day; all
other treated animals
survived
All animals survived
^
Damage in lungs only;
dust particles in
peribronchial & peri-
vascular tissues, as
well as in alveoli &
phagocytes; inflamma-
tion, edema, & thick-
, ening of alveolar walls ;
bronchial epithelial
desquamation &
hyperplasia
Significant Be levels in lungs with higher cone, present in
monkeys; no hlstological or ultrastructural pulmonary
changes; no changes in air-blood barrier thickness or
capillary-alveolar surface area ratio
Pulmonary edema in all treated animals at 15 day; peri-
bronchial lymphoid hyperplasia at 15-60 day in animals
receiving BeO calcined at 500 or 1100°C only; no specific
pulmonary reaction at 30-60 day with BeO calcined at
1600°C
1/4 deaths at 75 day from pneumonitis; pulmonary emphysema
& fibrosis; minimal extrapulmonary lesions
No deaths; 20% body wt loss, yg Be/g fresh tissue from
4 sacrificed animals; lung, 0.08; liver, 0.02; kidney,
0.01; spleen, 0.01
1 death; no change in body wt
4 deaths; 43% body wt loss
4- in RBC count & Hb levels ; t in mean corpuscular volume
consistent with macrocytic anemia; spontaneous recovery
u>
from anemia after 3.5-4 mo
(continued)
-------
TABLE 6.15 (continued)
Substance Animal
Beryllium 5 dogs, young
sulfate adult
20 guinea pigs,
400-600 g
34 guinea pigs,
400-600 g
12 guinea pigs,
400-600 g
10 guinea pigs,
400-600 g
83 hamsters
10 hamsters
38 mice
2 monkeys
Concentration
or dose
0.95 mg (0.04 mg
Be)/m3 in H20
10 mg (0.43 mg
Be)/m3 in H20
47 mg (2 mg
Be)/m3 in H20
0.95 mg (0.04 mg
Be)/m3 in H20
10 mg (0.43 mg
Be)/m3 in H20
47 mg (2 mg
Be)/m3 in H20
100 mg (4.3 mg
Be)/m3 in H20
0.95 mg (0.04 mg
Be)/m5 in H20
47 mg (2 mg
Be)/m3 in H20
100 mg (4.3 mg
Be)/m3 in H20
47 mg (2 mg
Be)/m3 in H20
100 mg (4.3 mg
Be)/m3 in H20
0.95 mg (0.04 mg
Be)/m3 in H20
Exposure Particle Effects
(duration) size (urn) trrects
6
6
6
6
6
6
6
6
6
6
6
6
6
hr/day 0.25
(100 day)
hr/day 1.5
(95 day)
hr/day 0.96
(51 day)
hr/day 0.25
(100 day)
hr/day 1.5
(95 day)
hr/day 0.96
(51 day)
hr/day 1.1
(14 day)
hr/day 0.25
(100 day)
hr/day 0.96
(51 day)
hr/day 1.1
(14 day)
hr/day 0.96
(51 day)
hr/day 1.1
(14 day)
hr/day 0.25
(100 day)
No deaths; 10% body wt loss. -^
yg Be/g fresh tissue from
5 sacrificed animals; lung,
0.06; pulmonary lymph nodes,
0.7; liver, 0.01; kidney,
0.003; spleen, 0.01
No deaths; 11% body wt loss;
leukocytosis , pg Be/g fresh
tissue from 4 sacrificed
animals: lung, 4; pulmonary
lymph nodes, 2; liver, 1.8;
kidney, 0.8; spleen, 0.004; j
femur, 0.8
4 deaths; 4% body wt loss;
leukocytosis
No deaths; 18% body wt gain
2 deaths; 100% body wt gain
7 deaths; 37% body wt gain
3 deaths; 2% body wt loss
No deaths; no change in body wt
5 deaths; 18% body wt loss
2 deaths; 8% body wt loss
4 deaths; 6% body wt loss
No deaths; 13% body wt loss
Reversible macrocytic
anemia after 3-8 wk;
significant changes in
phospholipid & free
cholesterol of whole
RBC; tendency to hypo-
s' albuminemia & hyperglobu
linemia; acute inflamma-
tory response in lung,
with erosion & prolifera
tion of bronchial
epithelium
No deaths; 10% body wt gain, yg Be/g fresh tissue from 2
sacrificed animals: lung, 1.2; pulmonary lymph nodes,
1.3; liver, 0.5; kidney, 0.01;
spleen, 0.1
UJ
Ln
(continued)
-------
TABLE 6.15 (continued)
Substance Animal
5 monkeys
1 monkey
Beryllium it monkeys
sulfate rhesus
23 rabbits,
2.6-4.0 kg
24 rabbits,
2.6-4.0 kg
10 rabbits,
2.6-4.0 kg
3 rabbits,
2.6-4.0 kg
20 rats,
250-280 g
40 rats
47 rats,
250-280 g
15 rats,
250-280 g
10 rats,
250-280 g
150 rats,
Sprague-
Dawley, 6 wk
Concentration
or dose
10 mg (0.43 mg
Be)/m3 in H20
47 mg (2 mg
Be)/m3 in H20
66 yg (5.6 ug
Be) /ft3 in
H20
0.95 mg (0.04 mg
Be)/m3 in H20
10 mg (0.43 mg
Be)/m3 in H20
47 mg (2 mg
Be)/m3 in H20
100 mg (4.3 mg
Be)/m3 in H20
0.95 mg (0.04 mg
Be)/m3 in H20
4 mg/m3 In H20
10 mg (0.43 mg
Be)/m3 in H20
47 mg (2 mg
Be)/m3 in H20
100 mg (4.3 mg
Be)/m3 in H20
34.2 yg Be/m3
Exposure
(duration)
6 hr/day
(95 day)
6 hr/day
(51 day)
6 hr/day
(7 day)
6 hr/day
(100 day)
6 hr/day
(95 day)
6 hr/day
(51 day)
6 hr/day
(14 day)
6 hr/day
(100 day)
6 hr/day
(23 wk)
6 hr/day
(95 day)
6 hr/day
(51 day)
6 hr/day
(14 day)
7 hr/day
5 da/wk
Particle
size (pm)
1.5
0.96
0.25
1.5
0.96
1.1
0.25
1.5
0.96
1.1
0.12
Effects
No deaths; 31% body wt loss
1 death; 25% body wt loss
1/4 deaths at 52 day from pneumonitis; pulmonary
emphysema, granulomas (1/4 at 6 mo), fibrosis;
desquamation of bronchial & bronchiolar epithelium;
marked lymph node hyperplasia (2/4) ; minimal extrapul-
monary lesions
No deaths; 15% body wt gain, ug Be/g fresh tissue from
5 sacrificed animals: lung, 1.6; pulmonary lymph nodes,
0; liver, 0.004; kidney, 0.003; spleen, 0.01
2 deaths ; no change in body wt ; leukocy tosls
1 death; 7% body wt gain; leukocy tosis
No deaths ; no change in body wt ; leukocy tosis
No deaths; 20% body wt gain
* in RBC count; + in mean corpuscular volume consistent
with macrocytlc anemia
23 deaths; 28% body wt gain; leukocytosls; inhalation of
HF vapor (8 mg/in3) doubles toxicity of BeSOi, poisoning
13 deaths; no change in body wt; leukocy tosis
10 deaths; 2% body wt loss; leukocytosis
t in mortality in 9 only; 100% alveolar adenocarcinomas
at 13 mo; t in Be content in lungs with cone plateau at
36 wk; significant 4- in Be content of excised tumors
compared to nonmalignant tissue; maximum Be levels in
tracheobronchial lymph nodes at 36-52 wk with greater
Be deposition in o"
u>
(continued)
-------
TABLE 6.15 (continued)
Substance
Beryllium chloride
(10%), beryllium
fluoride (40%),
& beryllium oxide
(50%) in rocket
exhaust
Animal
136 rats,
Wlstar &
Sherman,
140-210 g
2 dogs, beagle,
8.1-10.8 kg
Concentration
or dose
12 yg (1 yg
Be)/ft3 in
H20
115 mg Be/m3
Exposure Particle
(duration) size (pm)
8 hr/day
5.5 day/wk
(6 mo)
20 min <1 to >5
Effects
46 deaths. Apparent effect on lung tissue; stimulation
of epithelial cell proliferation without connective
tissue reaction; foam-cell clustering; focal mural
infiltration; lobular septal cell proliferation;
peribronchial alveolar wall epithelization; granulo-
matosis & neoplasia
3.9-5.5 ug Be/g wet lung at 3 yr; Be (<0.05-1 y) deposited
in histiocytlc lysosomes in septal interstltium in
association with collagen bundles & t in numbers of
septal capillaries
Source: Altman and Dittmer, 1973, pp. 954-958. Reprinted by permission of the publisher.
-------
138
ORNL-DWG 77-4510A
100
234 56
EXPOSURE (weeks)
Figure 6.8. Animal mortality rate following exposure to 47 mg of
BeSOi, per cubic meter by inhalation. Source: Stokinger et al., Arch.
Ind. Hyg. Occup. Med., April, Vol. 1, Figure 3, p. 385, Copyright 1950,
American Medical Association. Reprinted by permission of the publisher.
Monkeys (Maoaoa mulatto) exposed to beryllium fluoride, beryllium
sulfate, and beryllium phosphate developed symptoms related to the beryl-
lium content of the compound to which they were exposed (Schepers, 1964).
Beryllium fluoride (953 yg/m3) was the most toxic and beryllium phosphate
(2331 yg/m3) the least toxic. However, at high levels of phosphate (97
mg/m3), all the monkeys were killed within 20 days, and at a concentration
of 13 mg/m3 all animals died within 92 days. Beryllium fluoride and the
high concentrations of beryllium phosphate caused severe and universal pul-
monary reactions along with changes in the liver, kidneys, adrenals, pan-
creas, thyroid, and spleen. Animals exposed to beryllium sulfate (2330
yg/m3) had little sign of any illness. Spencer et al. (1972) demonstrated
that the beryllium oxide exhaust product from a beryllium-fueled NASA-JPL
high-energy upper-stage motor induced a less severe pulmonary response in
rats than did BeO calcined at 500°C. However, the pulmonary lesions were
histologically similar. Beryllium oxide calcined at 500, 1000, or 1600°C
endotracheally injected into guinea pigs produced a lung reaction morpho-
logically similar to that characteristic of delayed hypersensitivity reac-
tions (Chiappino, Cirla, and Vigliani, 1969). The most active oxide was
calcined at the lowest temperature and was the least crystalline and most
soluble. This graduation of toxicity of beryllium oxides according to
their firing temperatures appears to be related to the crystallite size of
the particles, with resultant variability of reactive surface. Optical
birefrigence is governed by the same parameters (Crossmon and Vandemark,
1954).
-------
139
6.3.3.5 Acute Effects in Experimental Animals — Beryllium produces toxic
effects at sites other than the skin and respiratory tract, as demonstrated
in research animals. Liver necrosis in rats was produced by a single intra-
venous dose of 1.1 mg of beryllium (as the sulfate) per kilogram of body
weight (Cheng, 1956). Gradual obliteration of liver sinusoids and terminal
development of hemorrhagic foci round terminal afferent vessels occurred,
with progressive damage to Kupffer cells and sinusoidal infiltration of
inflammatory cells. Degeneration and necrosis of parenchymal cells oc-
curred mainly in the periportal and middle zone of liver lobules. Circu-
latory disturbances were the result and not the cause of liver cellular
damage. Injection of BeSO*, also inhibits reticuloendothelial system activ-
ity, due to the phosphate fraction formed by the conversion of the sulfate
(Vacher, Deraedt, and Benzoni, 1973).
Changes occurred in the central nervous system of rabbits following
injection of beryllium (as the chloride or sulfate) into the cerebello-
medullary cistern or spinal subarachnoid space (Zelman et al., 1967).
Focal injury of the neurons connected with the injection site and inflam-
matory changes resembling granulomatosis were induced.
Stokinger and Stroud (1951) induced anemia in dogs, rats, and rabbits
by inhalation exposure to beryllium fluoride for 6 hr daily five days per
week for 23 weeks at a concentration of 2.2 ± 0.25 mg per cubic meter of
air. The anemia resembled the macrocytic type, was of a mild degree, and
differed between species. In the dog the red blood cell count (RBC), mean
corpuscular volume (MCV), and hemoglobin all changed in a manner typical
of nonnochromic macrocytic anemia. In the rabbit there was less tendency
for decreasing hemoglobin levels and a greater tendency to return to nor-
mal values, whereas in the rat, hemoglobin values were normal, while the
MCV and RBC count changed in consistency with macrocytic anemia.
6.3.4 Chronic Beryllium Disease
Chronic beryllium disease arises from inhalation of beryllium com-
pounds (Casarett and Doull, 1975). The chronic disease has a latent
period of up to more than 20 years, is of long duration, is progressive
in severity, and is a systemic disease (Tepper, Hardy, and Chamberlin,
1961). In some instances, the acute form of the disease may progress to
the chronic form (Hardy and Chamberlin, 1972) with an asymptomatic period
between recovery from the acute disease and onset of the chronic disease.
Although data exist for probable harmful and safe beryllium levels,
the dose necessary to produce chronic beryllium disease is not known
(Hardy and Chamberlin, 1972). Delay in disease onset and lack of data
from earlier cases has contributed to the lack of knowledge concerning
a dose-response relationship to the disease. However, since 1949, when
efforts began to control exposure, the number and severity of cases
decreased as concentrations decreased (Williams, 1959).
6.3.4.1 Incidence — The progress report of the U.S. Beryllium Case Reg-
istry, 1972, lists a total of 577 chronic cases occurring in the United
States; 44 cases are listed as both chronic and acute (Hasan and Kazemi,
1973). Standards for exposure were set in 1949 not to exceed 2 yg/m3 over
-------
140
an 8-hr period to eliminate the development of chronic beryllium disease.
However, since 1966, 76 new cases have been added to the Registry (Hasan
and Kazemi, 1974). Of these new cases, about half had significant expo-
sure since 1949; 17 were exposed after 1966, and 7 were exposed as late
as 1972, indicating that beryllium is still an industrial hazard despite
existing exposure standards, possibly because of occasional noncompliance.
Most exposures since 1950 have occurred in handling and processing beryl-
lium compounds in the aerospace and nuclear industries.
A detailed study of cases in the basic beryllium industry in north-
ern Ohio between 1940 and 1953 revealed a total incidence of 1.1% of all
personnel exposed prior to introduction of industrial hygiene controls of
an engineering type (DeNardi, 1959). The incidence rate for females was
3.2% and for males 0.68%, indicating a predilection for incidence in fe-
males. The overall mortality rate was 22%, with a 17% rate in men and
4.5% in women.
6.3.4.2 Induction and Mechanism of Delayed Response — Clary and Stokinger
(1973) proposed that the mechanism for disease onset involved some form of
stress such as respiratory infection, surgery, or pregnancy. The stress
leads to altered adrenal function, which is related to onset of the latent
chronic disease. Altered adrenal function results in beryllium translo-
cation to organs critical to systemic disease initiation. Liver enzyme
activity increases, body weight decreases, renal damage occurs, lysosomal
stability is reduced, and a linear correlation between beryllium and ste-
roid levels occurs in the liver. Figure 6.9 diagrammatically shows the
proposed steps leading to chronic beryllium disease. Mice and guinea pigs
with altered adrenal function have a more severe reaction to beryllium,
introduced as BeS04 or BeO by transthoracic or intratracheal injection,
than control animals, as demonstrated by weight loss, metal-ion shift, and
serum enzyme elevation (Clary, Hopper, and Stokinger, 1972).
ORNL-DWG 77-4517
TRIGGERING MECHANISM (INFECTION, SURGERY 1
ADRENAL IMBALANCE
+
TRANSLOCATION OF BERYLLIUM TO THE LIVER
S ^
INFLAMMATION LYSOSOMAL INSTABILITY
LYSOSOMAL RUPTURE
CELL DEATH
*
ONSET OF LATENT BERYLLIUM DISEASE
Figure 6.9. Proposed mechanism for the latency of chronic beryllium
disease. Source: Clary and Stokinger, 1973, Figure 2, p. 255. Reprinted
by permission of the publisher.
-------
141
Hall et al. (1959) reported pregnancy as a stress that precipitated
the disease. In 40% of the women with the chronic disease who became
pregnant following beryllium exposure, pregnancy or the immediate post-
partum period initiated or increased symptoms of the disease. Kidney
damage observed in pregnant rats receiving beryllium treatment (form and
dose level not given) indicated that pregnancy stress had a detrimental-
effect on the animal's response to beryllium (Clary and Stokinger, 1973).
However, Clary, Bland, and Stokinger (1975) later reported that there was
no difference in time of onset of beryllium disease, as indicated by lung
granuloma, between bred and unbred beryllium-treated rats. This suggested,
in opposition to their earlier findings, that pregnancy was a type of adre-
nal stress that did not induce latent chronic beryllium disease.
6.3.4.3 Diagnosis — Chronic beryllium disease is not always easy to diag-
nose (Hardy and Chamberlin, 1972), since abnormalities that occur are not
specific for this disease (Tepper, Hardy, and Chamberlin, 1961). Proper
diagnosis includes evidence from x rays, immunological tests, pulmonary
function tests, and establishment of beryllium exposure (U.S. Department
of Health, Education, and Welfare, 1972). Tissue analysis for beryllium
establishes exposure but does'not prove disease presence (Tepper, 1972&).
However, all chronic cases of the disease have yielded positive lung
tissue assays.
Along with establishment of exposure, clinical criteria that indi-
cate disease presence include scattered densities on chest x rays, impaired
lung function, interstitial pneumonitis, and systemic toxicity (Stoeckle,
Hardy, and Chang-Wai-Ling, 1975). Radiological diagnosis is important in
determining disease existence. Patterns associated with chronic beryl-
lium disease are nodular, granular, and mixed pattern fibrosis (Hasan
and Kazemi, 1974). Lesions of fine granular densities which diffusely
involve the lung parenchyma are the first roentgen evidence and appear
within a few weeks of symptom development (Chamberlin, G. W., 1959). A
relationship seems to exist between pulmonary pathology and prognosis
(Freiman and Hardy, 1970). In studying 124 chronic cases, those with
minimal interstitial cellular infiltration lived longer than those with
moderate to marked cellular infiltration (over 11 years as compared with
8 years). A problem in differentiating between chronic beryllium disease
and sarcoidosis exists, however, these two can be correctly diagnosed by
roentgenographic and clinical criteria (Israel and Sones, 1959). Weight
loss may be a distinguishing symptom, since it is found in beryllium
disease but not in sarcoidosis.
The beryllium patch test has been used as a diagnostic tool for
chronic beryllium disease determination. However, a positive test indi-
cates only skin sensitivity to beryllium and not necessarily disease pres-
ence (Curtis, 1959; Sarkar, Jones, and Lutwyche, 1971). The use of the
patch test has been discouraged, since it may induce a skin sensitivity
reaction (Sarkar, Jones, and Lutwyche, 1971).
6.3.4.4 Symptoms — The most common symptoms of the chronic disease are
dyspnea on exertion (Hardy, 1948) and a usually nonproductive cough (Hardy
and Stoeckle, 1959). Weight loss, fatigue, and anorexia also occur; the
mortality rate in this type of case is high, and some degree of permanent
-------
142
disability usually remains in all survivors (Greenburg, 1972). Table
6.16 lists the symptoms and their frequencies in 76 cases reported to the
Beryllium Case Registry since 1966. Along with these symptoms, renal cal-
culi and pneumothoraces were found (Hasan and Kazemi, 1974). The delay
of symptom onset from time of last exposure for patients exposed prior
to and after 1949 is shown in Figure 6.10. Most patients exposed prior
to 1949 had a delay period of more than ten years, whereas those exposed
after 1949 had a delay period of less than a year. This is attributed
to better diagnostic techniques, with earlier recognition of the disease.
Other symptoms that usually occur during the progress of the disease are
clubbing of fingers, lymphadenopathy, liver enlargement, skin lesions,
spleen enlargement, and thyroid gland enlargement (Hardy, 1950) .
TABLE 6.16. SYMPTOMS OF 76 CASES OF CHRONIC BERYLLIUM
DISEASE REPORTED TO THE BERYLLIUM CASE REGISTRY
SINCE 1966
Symptom Number of cases Percent
Exertional dyspnea
Cough
Fatigue
Weight loss
Chest pain
Arthralgia
Fever
Orthopnea
Anorexia
Hemoptysis
Palpitations
Convulsions
Wheezing
Nausea, . vomiting
Hoarseness
51
40
28
21
20
7
6
5
4
2
2
2
1
1
1
67.1
52.6
36.8
26.6
26.3
9.2
7.8
6.5
5.3
2.6
2.6
2.6
1.3
1.3
1.3
Source: Adapted from Hasan and Kazemi, 1974,
Table 2, p. 290. Reprinted by permission of the
publisher.
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143
ORNL-DWG 77-462(
1-5 5HO
ONSET OF SYMPTOMS
FROM LAST EXPOSURE (years)
Figure 6.10. Delay in symptom onset of 76 cases of chronic beryllium
disease reported to the Beryllium Case Registry since 1966. Source:
Adapted from Hasan and Kazemi, 1974, Figure 1, p. 290. Reprinted by per-
mission of the publisher.
Pulmonary changes from inhalation of beryllium compounds have occurred
in experimental animals. The changes are similar to those found in humans.
After inhalation of rocket exhaust products containing beryllium oxide,
beryllium fluoride, and beryllium chloride at an average concentration of
115 mg of beryllium per cubic meter, beagles had lung tissue lesions rep-
resentative of an early form of the chronic disease (Robinson, Schaffner,
and Trachtenberg, 1968). Sanders et al. (1974) and Sanders et al. (1975)
exposed rats and hamsters by inhalation to BeO calcined at 1000°C at con-
centrations ranging from 1 yg to 100 yg of beryllium per liter of air.
Rapid damage occurred to the alveolar macrophage, which eventually pro-
duced a mild granulomatosis reaction eight months after exposure.
Moderate skin reactions of delayed-type hypersensitivity may also
occur in the course of the disease (Alekseeva, Vasil'eva, and Orlova,
1974). This reaction is found also in experimental animals. Beryllium-
sensitized guinea pigs developed delayed hypersensitive skin reactions
when challenged with BeS04 and BeF2 (Marx and Burrell, 1973). Reactions
typical of beryllium granulomata occurred when the animals were chal-
lenged with BeO. In guinea pigs the delayed reaction results only from
skin contact with beryllium (Vacher, 1972), as is the case in humans
(Reeves and Krivanek, 1974). A relationship between cutaneous sensitiv-
ity and pulmonary beryllium disease appears to exist. The induction of
-------
144
cutaneous beryllium sensitivity in guinea pigs produces a protective ef-
fect against pulmonary disease development (Reeves et al., 1971; Reeves
et al., 1972). Hypersensitivity induction appears to provide resistance
to the fibrotic and metaplastic effects of beryllium inhalation (Reeves
and Krivanek, 1974). This may be significant in the prophylaxis of
beryllium-exposed humans. Dudley (1959) attributed responsibility for
many of the symptoms to a variable infiltration of lymphocytes and plasma
cells in the tissues where the chronic reaction takes place.
6.3.4.5 Complications — The prominent complication in chronic beryllium
disease is the development of cor pulmonale. Death can frequently be
attributed to cor pulmonale with myocardial decomposition (Tepper, Hardy,
and Chamberlin, 1961). Of 45 cases of the chronic disease, cor pulmonale
was observed in 33% of the patients (Konchalovskaya and Glotova, 1969;
Orlova and Glotova, 1969). The frequency and intensity increased with
increased severity of pulmonary insufficiency. Kelley, Goldfinger, and
Hardy (1969) reported hyperuricemia in 40% (6 of 15) of the patients exam-
ined. The elevated serum urate resulted from diminished renal clearance
of uric acid rather than increased production of the compound.
6.3.4.6 Industrial and Neighborhood Cases — Chronic beryllium disease has
been associated with most industries in which beryllium is used. Table
6.17 gives the mortality of the chronic disease by industry. From 1960 to
1968, 41 patients with the disease were examined at Massachusetts General
Hospital (Andrews, Kazemi, and Hardy, 1969). Three different pulmonary
dysfunction patterns were observed: obstructive, interstitial, and restric-
tive defects. These appeared to correlate with the anatomic lung altera-
tions. As seen in Table 6.18, most of the exposures, 27 of 41, occurred
in fluorescent lamp manufacturing. Smoking habits were taken into account
and seemed to play a part in the appearance of the obstructive pattern in
some of the patients. A case of the chronic disease, which had been on-
going for ten years, was observed in Spain (Matilla et al., 1973). The
case was not diagnosed until hospital admittance, at which time the patient
showed labial cyanosis, cough, dyspnea, a tender epigastrum, and rales.
The patient had been exposed for 14 years while working in a French elec-
trical appliance factory.
A study of a beryllium extraction and processing plant in operation
for 14 years revealed 31 cases of the chronic disease out of 214 workers
studied; 2 cases appeared between 1971 and 1973 (Kanarek et al., 1973).
These 31 had radiographic abnormalities compatible with interstitial dis-
ease, and 11 of the 31 had hypoxemia. The beryllium air levels usually
exceeded the standard of 2 yg/m3; they ranged from 0.35 to 213 yg/m3 in
the billet plant and 0.31 to 1310 yg/m3 in the fabrication plant.
A case of beryllium skin granuloma due to beryllium oxide was reported
(Williams, Lawrie, and Davies, 1967; Williams, 1971). The patient cut his
finger on a grinding wheel contaminated with the compound. This led to
amputation of the finger and lymphatic spread of beryllium to produce gran-
ulomata of the forearm and lung.
Cases of chronic beryllium disease have been reported in the vicinity
of industrial sources (Hardy and Chamberlin, 1972). Thus far, 45 cases
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145
TABLE 6.17. MORTALITY OF CHRONIC BERYLLIUM
DISEASE BY INDUSTRY UP TO 1966
Number
Percent dead
Living Dead
Total
Extraction-smelting
Fluorescent lamp
Atomic energy
Neon tube
Ceramics
Foundry-machining
Cathode- tubes
Alloy
Tube disposal
Other
Total workers
57
170
33
8
12
12
ii
3
2
3
311
21
79
6
15
19
9
8
10
7
0
164
27
32
15
65
43
43
42
77
78
0
35
78
249
39
23
21
21
19
13
9
3
475
Source: Adapted from Redding, Harding, and Gaensler,
1968, Table 11, p. 272. Reprinted by permission of the
publisher.
have been reported in persons living within 1/2 mile of the source or in
persons handling contaminated clothing of workers. As early as 1949,
neighborhood cases were reported (Eisenbud et al., 1949). Eleven cases
were observed near a processing plant; ten of the patients resided within
3/4 mile of the plant. The eleventh patient's disease was thought to re-
sult from contamination introduced into the home by worker's clothes.
Lieben and Williams (1969) reported a total of 29 neighborhood cases around
a beryllium refinery. Some of these patients lived more than 3 miles away
but came within 1/2 mile of the refinery routinely. These neighborhood
cases of beryllium disease are thought to have occurred from close contact
with a contaminated person or object rather than from general air pollu-
tion (Preuss, 1975).
6.3.4.7 Treatment — Prior to treatment with steroids (Seeler, 1959) and
adrenocorticotropic hormone (ACTH), chronic beryllium disease treatment
consisted of bed rest and oxygen administration (Tepper, Hardy, and
Chamberlin, 1961). Now, long-term therapy with daily doses of steroids
in the range of 75 to 150 mg or more has proven effective (Hardy and
Chamberlin, 1972).
-------
146
TABLE 6.18. CLINICAL DATA OH PATIENTS WITH CHRONIC BERYLLIUM DISEASE
Patient Age Sex Type of exposure
Duration of
exposure (years)
Delay in onset
from first
exposure (years)
Smoking
history
Last tests
(years after
first exposure)
S.R.
H.D.
E.I.
P.P.
D.B.
J.C.
L,W.
W.D.
P.K.
W.G.
S.A.
F.B.
M.S.
S.N.
W.J.
P.T.
G.R.
A..Z.
P.S.
E.H.
M.H.
M.F.
T.C.
J.S.
48
47
42
42
45
43
66
58
54
58
49
50
48
35
53
52
58
51
51
26
52
35
44
57
Interstitial group
F
F
F
F
F
M
H
M
M
M
M
F
M
F
M
F
Fluorescent lamp
Fluorescent lamp
Fluorescent lamp
Fluorescent lamp
Fluorescent lamp
Fluorescent lamp
Atomics
Atomics
Fluorescent lamp
Fluorescent lamp
Atomics
Fluorescent lamp
Beryllium alloy
Fluorescent lamp
Ceramics
Fluorescent lamp
M Foundry
F Fluorescent lamp
M Fluorescent lamp
M Foundry
F Fluorescent lamp
F Fluorescent lamp
M Fluorescent lamp
H Ceramics
4
9
7
0.5
2
1
2
0.5
1
10
0.5
1
19
2
3
2
Restrictive group
8
9
1
0.5
3
3
2
1
8
12
11
11
9
5
22
0.5
5
5
5
18
15
12
15
6
9
22
None
(immediate)
19
12
13
Obstructive group
0
0
-tO'60
0
0
28
28
23
24
24
24
23
24
26
21
23
20
18
37
28
28
29
5
24
20
18
L.H.
M.C.
L.S.
E.G.
A.S.
E.U.
N.S.
M.B.
D.M.
B.C.
F.G.
V.M.
K.K.
J.V.
M.C.
C.F.
L.R.
45
43
43
47
47
39
45
48
47
38
45
53
45
40
40
51
39
M
F
F
F
M
F
F
F
F
F
M
M
F
F
F
F
M
Fluorescent lamp
Fluorescent lamp
Fluorescent lamp
Fluorescent lamp
Fluorescent lamp
Ceramics
Fluorescent lamp
Fluorescent lamp
Metal (beryllium)
Fluorescent lamp
Ceramics
Ceramics
Atomics
Fluorescent lamp
Fluorescent lamp
Fluorescent lamp
Atomics
2.5
5
1.5
3
3
4.5
1
1
3
5
5
2
1
1.5
Normal group
8
1
8
6
9
15
3
4
24
8
8
9
23
18
+
0
+
0
0
+
_
0
40
-
-tO '65
-
0
+0'58
+
0
28
28
26
28
26
19
25
26
20
20
23
24
17
24
18
Source: Adapted from Andrews, Kazemi, and Hardy, 1969, Table 1, p. 792.
of the. publisher.
Reprinted by permission
A patient with the chronic disease received treatment with predni-
sone at 60 mg/day, which was reduced to 15 rag/day over a four-month period
(Henderson, 1970). As a result of treatment, clinical, radiological, and
lung function improvement followed. Symptoms reoccurred as the dosage
decreased; hence it was necessary to keep the patient on a 15-mg/day dose.
Another patient was relieved of symptoms on a maintenance dose of 20 mg/day
of prednisone (Neff and Petty, 1969). Treatment with steroids on a con-
tinued basis has led to marked improvement in patients; however, because
of the long duration of the disease, total cure cannot be established (U.S.
Department of Health, Education, and Welfare, 1972).
-------
147
Chelating agents for removal of deposited tissue beryllium have been
explored. Among these, aurintricarboxylic acid proved effective in pro-
tecting mice and rats if given parenterally 1 to 8 hr after intravenous
injection of an otherwise lethal dose of beryllium sulfate. The chelate
tended to accumulate in the kidneys and spleen (White, Finkel, and Schubert,
1951; Schubert, White, and Lindenbaum, 1952; Schubert and Rosenthal, 1959).
In the Soviet Union, organophosphorus complexons were tried in animal exper-
iments (Arkhipova, Zel'tser, and Petushkov, 1966). However, for the alle-
viation of the chronic disease, chelating agents have proved thus far
ineffective, and clinical trials were disappointing (Dequindt and Haguenoer,
1973).
6.3.5 Carcinogenesis
Experimental findings show that beryllium compounds are capable of
producing malignant tumors in experimental animals (Vorwald, Reeves, and
Urban, 1966). Of all the beryllium compounds tested, only five have been
shown carcinogenic: beryllium oxide, beryllium sulfate, beryllium fluo-
ride, beryllium phosphate, and the phosphor zinc manganese beryllium sili-
cate (Schepers, 1961). A summary of experimental beryllium carcinogenicity
is provided in Table 6.19. Tumors induced in species in the above table
include adenocarcinoma, epidermoid carcinoma, mixed carcinoma, pleural
mesothelioma, alveolar cell carcinoma, reticulum cell sarcoma of lymph
nodes, and osteogenic sarcoma.
6.3.5.1 Human Carcinogenesis — Counterparts to cancers produced in experi-
mental animals by beryllium have not been observed in humans (U.S. Depart-
ment of Health, Education, and Welfare, 1972). Epidemiological studies to
show a relationship between beryllium exposure and cancer incidence have
not provided data for the existence of such a relationship (International
Agency for Research on Cancer, 1972). The fact that human beryllium cancer
has not been identified, however, may be a result of chemical carcinogens
not remaining at the cancer site. The causative agent often cannot be
identified except through work histories. Hence, beryllium may be over-
looked as a causal agent.
Cancer has been reported among beryllium workers, although a direct
relationship lacks proof. Mancuso and El-Attar (1969) studied the cancer
incidence of workers in two beryllium companies and reported no correlation
between cancer at any specific site and the worker's beryllium exposure.
In contrast, two cases of delayed lung carcinoma induced by beryllium aero-
sol were reported by Niemoller (1963). In each case the carcinoma was
detected 16 years after the last exposure. No incidence rates were given,
and no correlation between beryllium and cancer rate could be concluded.
In a retrospective study of employees in two beryllium companies, Mancuso
(1970) reported a higher rate per 100,000 for lung cancer among the workers
with prior respiratory illness than among the total workers. Mancuso sug-
gested that prior chemical respiratory illness may influence the develop-
ment of lung cancer among beryllium workers.
6.3.5.2 Pulmonary Cancer — Development of pulmonary cancer generally re-
quires 7 to 13 months in rats and four to five years in monkeys (Vorwald,
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148
TABLE 6.19. BERYLLIUM COMPOUNDS EXPLORED FOR CARCINOGENICITY
Substance
Fluoride
Metal
Hydroxide
Oxide
Carbide
Phosphate
Silicate
(ZnMnBeSiO,,)
Sulfate
Animal
species
Rat
Monkey
Guinea pig
Guinea pig
Guinea pig
Rabbit
Rabbit
Guinea pig
Guinea pig
Guinea pig
Guinea pig
Rabbit
Rat
Rat
Guinea pig
Rat
douse
Guinea pig
Rabbit
Rat
Pig
Monkey
Rat
Rat
Rat
Guinea pig
Rabbit
Rabbit
Rabbit
Dog
Guinea pig
Guinea pig
Guinea pig
Rat
Monkey
Pig
Rabbit
Guinea pig
Route
Inhalation
Inhalation
Subcutaneous
Intratracheal
Intraperitoneal
Intravenous
Intravenous
Intraperitoneal
Intratracheal
Intraperitoneal
Intratracheal
Intravenous
Intravenous
Inhalation
Intraperitoneal
Intravenous
Intravenous
Intracardiac
Intravenous
Inhalation
Subcutaneous
Inhalation
Intravenous
Intratracheal
Inhalation
Intratracheal
Intravenous
Intraperitoneal
Inhalation
Intravenous
Inhalation
Intracardial
Inhalation
Inhalation
Inhalation
Subcutaneous
Intravenous
Intratracheal
Concentration
or dosage
48 ug/m3
953 ug/m3
1 mg
75 mg
200 mg
1 g
100 mg
200 mg
150 mg
200 mg
150 mg
1 g
65 mg
28 mg/m3
200 mg
5 mg
1 mg
25 mg
100 mg
3.5 mg/m3
1 mg
0.9 mg/kg
80 mg
20 mg
25 mg/m3
150 mg
1 8
40 mg
25 mg/m3
1-3 g
25 mg/m3
80 mg
424 ug/m3
424 ug/m3
424 ug/m3
1 mg
100 mg
150 mg
Duration
(months) Carcinogenesis
15 +
5
12
3
5
8
2
7
4
7
9
12 +
8
12
5
2/3
2/3
2/3
10
12 +
12
4 +
12
12
9 +
12
10 +
12
24
40
22
4
12
18 +
8
12
25
12
Source: Schepers, 1961, Table 11, p. 208. Reprinted by permission of the publisher.
Reeves, and Urban, 1966). Vorwald (1967) exposed 16 rhesus monkeys to
BeSO/, mist at an atmospheric level of 35 ng of beryllium per cubic meter
of air for 6 hr daily, five days a week. The first pulmonary cancer
occurred in a male exposed for 3241 hr. Over a period of the next four
years, seven other monkeys developed lung cancer. One female monkey did
not develop cancer after 3303 hr of exposure. The remaining monkeys died
of acute chemical pneumonitis early in the study.
Numerous reports exist on the development of pulmonary cancer in
beryllium-exposed rats. Wagner et al. (1969) produced pulmonary tumors
in 18 of 19 rats that survived 17 months of exposure to 15 mg of beryl per
cubic meter. One hundred fifty rats were exposed to BeSO/. aerosol at an
atmospheric concentration of 34.25 yg of beryllium per cubic meter for 72
weeks (Reeves, Deitch, and Vorwald, 1967). A proliferative response con-
sisting of epithelial hyperplasia commenced rapidly at four weeks after
initial exposure. This response progressed through metaplasia and ana-
plasia to lung cancer, with the first tumors found after nine months of
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149
exposure. At 13 months the incidence rate reached 100%, vs 0% in con-
trols. All tumors were alveolar adenocarcinomas, with focal intermixture
of other kinds in some instances. Rats given 5 ppm beryllium as the sul-
fate in drinking water developed tumors of which 44% and 57% were malig-
nant in males and females, respectively (Schroeder and Kitchener, 1975a).
Data were not given concerning kind or site of tumors.
Intratracheal injections of beryllium in rats have induced cancers.
Beryl ore, BeO, Be(OH)2, beryllium metal, chromium-passivated beryllium
metal, and beryllium-aluminum alloy produced adenomas, adenocarcinomas,
and epidermoid carcinomas in rats given single injections of these sub-
stances (Groth, Stettler, and MacKay, 1976). The age of the rat and dose
of the compound determine the size, number, and quality of the lesions
produced. Twelve- and three-month-old rats injected with 40, 4, or 0.4
yg of beryllium as Be(OH)3 had one adenocarcinoma in the oldest group
receiving the highest dose. The greatest number of metaplastic foci oc-
curred in the older rats at doses of 40 and 4 yg; none were formed at 0.4
yg exposure. Four micrograms was the lowest dose that induced mast cell
and lymphocytic infiltrates, and interstitial fibrosis and proteinaceous
material in the alveoli (Groth, Scheel, and MacKay, 1972). Metaplasia,
produced with the 4-yg dose, is a consistent feature of low-level expo-
sures and is probably a precursor to cancer (Groth and Mackay, 1971).
Rat pulmonary tumors, bronchiolar alveolar cell tumors, and mixed adeno-
carcinoma-bronchiolar alveolar cell tumors have been induced by doses of
0.25 mg of Be(OH)2 administered by single injection (Mackay, Groth, and
Mead, 1970).
6.3.5.3 Sarcoma in Rabbits — Sarcomas in rabbits have been induced by
injection of zinc beryllium silicate and beryllium oxide; histologically
they are of three types: chondroblastic, osteoblastic, and fibroblastic
(Vorwald, Reeves, and Urban, 1966). Osteogenic sarcomas' developed in six
of nine rabbits administered serial intravenous injections of Be(OH)2 or
a phosphor containing Be(OH)2 three times a week from six to eight weeks
(Dutra and Largent, 1950). Tumors appeared within a period of 16 months
after the initiation of treatment (Table 6.20). Analysis of tumor tissue
showed that the tumors contained little beryllium. Tumors transplanted
from one animal into the anterior chamber of the eyes of guinea pigs con-
tinued to grow, thus indicating that once established, tumor growth was
independent of the presence of beryllium. Higgins, Levy, and Yollick
(1964) also successfully transplanted beryllium-induced chondrosarcoma
tumors from the host rabbit into the anterior eye chamber of recipient
rabbits.
Sarcomas formed in 4 of 12 rabbits injected with 20 mg of zinc beryl-
lium silicate into the medullary cavity of the upper end of the right tibia
(Tapp, 1966). The tumors formed 12 to 15 months after injection, and in
appearance they resembled bone sarcomas found in man. All tumors metas-
tasized to the lungs and in some cases into the parietal pleura and hilar
lymph nodes. Tapp (1969a) also produced osteogenic sarcomas in 4 of 18
rabbits 10 to 25 months after implantation of 10 mg of zinc beryllium sil-
icate, beryllium silicate, or beryllium oxide. These tumors metastasized
into the lungs. The initial reactions to beryllium salt implantation was
-------
TABLE 6.20. OSTEOSARCOMAS INDUCED BY BERYLLIUM
Rabbit
number
Be 17
Be 24
Be 26
Be 29
Be 31
Be 27
Be 4
Be 23
Be 28
Substance
(1% suspension in
saline solution)
Phosphor
BeO
BeO
BeO
Phosphor
BeO
Phosphor
BeO
BeO
Dose
(ml)
8
8
5
7.5
8
5
7
6-7
7.5
Number
of
doses
21
23
20
26
25
20
17
21
24
Total amount
of beryllium
(g)
0.09
0.66
0.36
0.70
0.08
0.36
0.064
0.50
0.58
Date of
first dose
8/14/47
8/14/47
9/15/47
9/15/47
9/17/47
9/15/47
8/27/47
8/14/47
9/15/47
Date of
last dose
10/3/47
10/6/47
11/3/47
11/15/47
11/15/47
11/15/47
10/6/47
10/3/47
11/15/47
Date
tumor found
8/16/48
10/16/48
8/27/48
9/14/48
9/2/48
10/13/48
a
&
b
a.
No tumors found.
Tumors found after paper was submitted for publication.
Source: Adapted from Dutra and Largent, 1950, Table 1, p. 198.
publisher.
Reprinted by permission of the
Ln
o
-------
151
a granulomatous reaction, which was most marked with beryllium silicate
and least with beryllium oxide (Tapp, 1969&). The granulomatous reaction
decreased three to six months after administration; however, focal accu-
mulations of beryllium-containing macrophages remained in the medullary
cavity. Following intramedullary injection of zinc beryllium silicate
and engulfment by macrophages, the beryllium salt crystal appears to pro-
vide a prolonged release of beryllium ions, which destroy the host cell
(Schneider, Resnick, and Wellmann, 1973). This reaction seems to provide
a stimulus for new bone formation following beryllium administration by
intravenous or intramedullary injection.
6.3.6 Teratogenicity and Mutagenicity
No data exist concerning the teratogenic or mutagenic effects or
lack of these effects by beryllium in humans or other mammals.
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152
SECTION 6
REFERENCES
1. Aldridge, W. N. 1966. The Toxicity of Beryllium. Lab. Invest.
15:176-180.
2. Aldridge, W. N., and M. Thomas. 1966. The Inhalation of Phospho-
glucomutase by Beryllium. Biochem. J. 98:100-104.
3. Alekseeva, 0. G. 1965. Ability of Beryllium Compounds to Cause
Allergy of the Delayed Type. Proc. Fed. Am. Soc. Exp. Biol. (trans.
suppl.) 25:T843-T846. Translated from Gig. Tr. Prof. Zabol. 1975.
9:20-23.
4. Alekseeva, 0. G., E. V. Vasil'eva, and A. A. Orlova. 1974. Aboli-
tion of Natural Tolerance and the Influence of the Chemical Allergen
Beryllium on Autoimmune Processes. Bull. Organ, mond. Sante, Bull.
W. H. 0. (Switzerland) 51:51-58.
5. Altman, P. L., and D. S. Dittmer. 1973. Biology Data Book. 2nd ed.
Vol. 2. Federation of American Societies for Experimental Biology,
Bethesda, Maryland, pp. 923-958.
6. Andrews, J. L., H. Kazemi, and H. L. Hardy. 1969. Patterns of Lung
Dysfunction in Chronic Beryllium Disease. Am. Rev. Respir. Dis.
100:791-800.
7. Arkhipova, 0. G., and N. K. Demokidova. 1967. The Action of Organo-
phosphorus Complexons on the Alkaline Phosphatase Activity Following
Beryllium Poisoning. Farmakol. Toksikol. (Moscow) 30:352-356.
8. Arkhipova, 0. G., M. R. Zel'tser, and A. A. Petushkov. 1966. Elimi-
nation of Radioactive Beryllium from Mice Under the Influence of
Complexing Compounds. Radiobiologiya 6:754-755.
9. Bamberger, C. E., J. Botbol, and R. L. Cabrini. 1968. Inhibition
of Alkaline Phosphatase by Beryllium and Aluminum. Arch. Biochem.
Biophys. 123:195-200.
10. Bassleer, R. 1965. Effets due Beryllium sur la Synthese des Pro-
teines Nucleiques et 1'Acide Deoxyribonucleique en Cellules Fibro-
blastiques Cultivees In Vitro (Effects of Beryllium on Nucleoprotein
and Nucleic Acid Synthesis in Tissue Culture of Fibroblasts) . Compt.
Red. Soc. Biol. 159:1620-1623.
11. Bellies, R. P. 1975. Metals. In: Toxicology. The Basic Science
of Poisons, L. J. Casarett and J. Doull, eds. Macmillan Publishing
Co., Inc., New York. p. 454.
12. Belman, S. 1969. Beryllium Binding of Epidermal Constituents. J.
Occup. Med. 11:175-183.
-------
153
13. Berry, J. W., D. W. Osgood, and P. A. St. John. 1974. Chemical
Villains. A Biology of Pollution. C. V. Mosby Company, Saint
Louis, pp. 87-89.
14. Browning, E. 1969. Toxicity of Industrial Metals. Butterworth
and Co., Ltd., London, pp. 67-86.
15. Casarett, L. J., and J. Doull. 1975. Toxicology of the Respiratory
System. In: Toxicology. The Basic Science of Poisons, L. J.
Casserett and J. Doull, eds. Macmillan Publishing Co., Inc., New
York. pp. 219-220.
16. Chamberlin, G. W. 1959. Radiological Diagnosis of Chronic Beryl-
lium Disease. Arch. Ind. Health 19:126-131.
17. Chamberlin, R. I. 1959. The Control of Beryllium Machining Opera-
tions. Arch. Ind. Health 19:231-238.
18. Cheng, K.-K. 1956. Experimental Studies on the Mechanism of the
Zonal Distribution .of Beryllium Liver Necrosis. J. Pathol. Bacteriol.
71:265-276.
19. Chevremont, M., and H. Firket. 1951. Action of Beryllium on Cells
Cultivated -In vitro; Effect on Mitosis. Nature (London) 167:772.
20. Chiappino, G., G. Barbiano di Belgiojoso, and A. M. Cirla. 1968.
Hypersensitivity to Beryllium Compounds: Inhibition of Intradermal
Reaction in Guinea Pigs by Anti-Lymphocyte Serum. Boll. 1st.
Sieroter. Milan. 47:669-677.
21. Chiappino, G., A. Cirla, and E. C. Vigliani. 1969. Delayed-Type
Hypersensitivity Reactions to Beryllium Compounds. Arch. Pathol.
87:131-140.
22. Cholak, J., R. A. Kehoe, L. H. Miller, F. Princi, and L. J. Schafer.
1962. Toxicity of Beryllium. Final Technical Engineering Report.
ASD-TR-62-7-665, Kettering Laboratory, University of Cincinnati,
Ohio. 69 pp.
23. Cikrt, M., and V. Bencko. 1975. Biliary Excretion of 7Be and Its
Distribution after Intravenous Administration of 7BeCl2 in Rats.
Arch. Toxicol. 34:53-60.
24. Cirla, A. M., G. Barbiano di Belgiojoso, and G. Chiappino. 1968.
Hypersensitivity to Beryllium Compounds: Passive Transfer in Guinea
Pigs by Lymphoid Cells. Boll. 1st. Sieroter. Milan. 47:663-668.
25. Clary, J. J., L. S. Bland, and H. E. Stokinger. 1975. The Effect
of Reproduction and Lactation on the Onset of Latent Chronic Beryl-
lium Disease. Toxicol. Appl. Pharmacol. 33:214-221.
26. Clary, J. J., and D. H. Groth. 1973. Comparative Changes in Serum
Enzyme Levels in Beryllium- or Carbon Tetrachloride-Induced Liver
Necrosis. Proc. Soc. Exp. Biol. Med. 143:1207-1210.
-------
154
27. Clary, J. J., C. R. Hopper, and H. E. Stokinger. 1972. Altered
Adrenal Function as an Inducer of Latent Chronic Beryllium Disease.
Toxicol. Appl. Pharmacol. 23:365-375.
28. Clary, J. J., and H. E. Stokinger. 1973. The Mechanism of Delayed
Biologic Response Following Beryllium Exposure. J. Occup. Med.
15:255-259.
29. Cralley, L. J. 1972. Uses and Industrial Exposures. In: The
Toxicology of Beryllium, I. R. Tabershaw, ed. Public Health Ser-
vice Pub. No. 2173, Washington, D.C. pp. 1-4.
30. Crossmon, G. C., and W. C. Vandemark. 1954. Microscopic Observa-
tions Correlating Toxicity of Beryllium Oxide with Crystal Structure.
Arch. Ind. Hyg. Occup. Med. 9:481-487.
31. Crowley, J. F., J. G. Hamilton, and K. G. Scott. 1949. The Metab-
olism of Carrier-free Radioberyllium in the Rat. J. Biol. Chem.
177:975-984.
32. Curtis, G. H. 1951. Cutaneous Hypersensitivity due to Beryllium.
Arch. Dermatol. Syphilol. 64:470-482.
33. Curtis, G. H. 1959. The Diagnosis of Beryllium Disease, with
Special Reference to the Patch Test. Arch. Ind. Health 19:150-153.
34. DeNardi, J. M. 1959. Long-Term Experience with Beryllium Disease.
Arch. Ind. Health. 19:110-116.
35. Deodhar, S. D., B. Barna, and H. S. Van Ordstrand. 1973. A Study
of the Immunologic Aspects of Chronic Berylliosis. Chest 63:309-313.
36. Dequindt, J., and J. Haguenoer. 1973. Les Effets des Quelques
Detoxifiants dans I1Intoxication Experimental de Beryllium (Effects
of Detoxifying Agents on Experimental Beryllium Poisoning). Arch.
Mai. Prof. Mgd. Trav. Secur. Soc. 34:493-502.
37. Donaldson, H. M. 1959. Problems in the Control of Operations in
a Beryllium-Processing Plant. Arch. Ind. Health 19:221-224.
38. Dudley, H. R. 1959. The Pathologic Changes of Chronic Beryllium
Disease. Arch. Ind. Health 19:184-187.
39. Dutra, F. R., and E. J. Largent. 1950. Osteosarcoma Induced by
Beryllium Oxide. Am. J. Pathol. 26:197-209.
40. Eisenbud, M., R. C. Wanta, C. Dustan, L. T. Steadman, W. B. Harris,
and B. S. Wolf. 1949. Non-Occupational Berylliosis. J. Ind. Hyg.
Toxicol. 31:282-294.
41. Epstein, A. 1959. Problems in the Safe Operation of Certain
Beryllium-Using Processes. Arch. Ind. Health 19:225-230.
-------
155
42. Freiman, D. G., and H. L. Hardy. 1970. Beryllium Diseases. The
Relation of Pulmonary Pathology to Clinical Course and Prognosis
Based on a Study of 130 Cases from the U.S. Beryllium Case Regis-
try. Hum. Pathol. 1:25-44.
43. Furchner, J. E. , C. R. Richmond, and J. E. London. 1973. Compara-
tive Metabolism of Radionuclides in Mammals: VII. Retention of
Beryllium in the Mouse, Rat, Monkey, and Dog. Health Phys. 24:292-300.
44. Goldblatt, P. J., M. W. Lieberman, and H. Witschi. 1973. Beryllium-
Induced Ultrastructural Changes in Intact and Regenerating Liver.
Arch. Environ. Health 26:48-56.
45. Greenburg, L. 1972. The Classification of Dusts Which Cause Pul-
monary Disability. J. Occup. Med. 14:146-148.
46. Griggs, K. 1973. Toxic Metal Fumes from Mantle-Type Camp Lanterns.
Science 181:842-843.
47. Groth, D. H., and G. R. Mackay. 1971. Chronic Pulmonary Pathology
in Rats After the Intratracheal Injection of 0.4, 4, and 40 yg of
Beryllium as Beryllium Hydroxide. Toxicol. Appl. Pharmacol. 19:392.
48. Groth, D. H., L. D. Scheel, and G. R. Mackay. 1972. Comparative
Pulmonary Effects of Beryllium and Arsenic Compounds in Rats. Lab.
Invest. 26:477-478.
49. Groth, D. H., L. Stettler, and G. Mackay. 1976. Interactions of
Mercury, Cadmium, Selenium, Tellurium, Arsenic and Beryllium. In:
Effects and Dose-Response Relationships of Toxic Metals, G. F.
Nordberg, ed. Elsevier Scientific Publishing Co., New York.
pp. 527-543.
50. Hall, T. C., C. H. Wood, J. D. Stoeckle, and L. B. Tepper. 1959.
Case Data from the Beryllium Registry. Arch. Ind. Health 19:100-103.
51. Hamilton, A., and H. L. Hardy. 1974. Industrial Toxicology. 3rd
ed. Publishing Sciences Group, Inc., Acton, Mass. pp. 43-58.
52. Hanifin, J. M., W. L. Epstein, and M. J. Cline. 1970. In Vitro
Studies of Granulomatous Hypersensitivity to Beryllium. J. Invest.
Dermatol. 55:284-288.
53. Hardy, H. L. 1948. Delayed Chemical Pneumonitis in Workers Exposed
to Beryllium Compounds. Am. Rev. Tuberc. 57:547-556.
54. Hardy, H. L. 1950. Clinical and Epidemiologic Aspects. In: Pneu-
moconiosis. Beryllium Bauxite Fumes. Compensation, A. J. Vorwald,
ed. Paul B. Hoeber, Inc., New York. pp. 133-151.
55. Hardy, H. L., and R. I. Chamberlin. 1972. Beryllium Disease. In:
The Toxicology of Beryllium, I. R. Tabershaw, ed. Public Health
Service Publication No. 2173, Washington, D.C. pp. 5-16.
-------
156
56. Hardy, H. L., and J. D. Stoeckle. 1959. Beryllium Disease. J.
Chronic Dis. 9:152-160.
57. Hasan, F. M., and H. Kazemi. 1973. Progress Report. U.S. Beryl-
lium Case Registry, 1972. Am. Rev. Respir. Dis. 108:1252-1253.
58. Hasan, F. M., and H. Kazemi. 1974. Chronic Beryllium Disease: A
Continuing Epidemiologic Hazard. Chest 65:289-293.
59. Hashimoto, T., J. G. Joshi, C. del Rio, and P. Handler. 1967.
Phosphoglucomutase: IV. Inactivation by Beryllium Ions. J. Biol.
Chem. 242:1671-1679.
60. Hazard, J. B. 1959. Pathologic Changes of Beryllium Disease.
Arch. Ind. Health 19:179-183.
61. Heindl, R. A. 1970. Beryllium. In: Mineral Facts and Problems.
Bureau of Mines Bulletin 650. Supt. of Documents, U.S. Government
Printing Office, Washington, D.C. 1291 pp.
62. Henderson, A. H. 1970. Chronic Beryllium Disease: A New Case
Following Exposure in 1961. Br. J. Dis. Chest 64:169-173.
63. Henderson, W. R., K. Fukuyama, W. L. Epstein, and L. E. Spitler.
1972. In Vitro Demonstration of Delayed Hypersensitivity in
Patients with Berylliosis. J. Invest. Dermatol. 58:5-8.
64. Higgins, G. M., B. M. Levy, and B. L. Yollick. 1964. A Trans-
plantable Beryllium-Induced Chondrosarcoma of Rabbits. J. Bone J.
Surg. 46-A:789-796.
65. Higgins, I.T.T. 1968. Beryllium Poisoning. Med. Times 96:25-34.
66. Hinman, R. W., T. A. Lynde, G. B. Pelleu, and R. W. Gaugler. 1975.
Factors Affecting Airborne Beryllium Concentrations in Dental Spaces.
J. Prosthet. Dent. 33:210-215.
67. Hyatt, E. C., H. F. Schulte, R. N. Mitchell, and E. P. Tangman. 1959.
Beryllium: Hazard Evaluation and Control in Research and Development
Operations. Arch. Ind. Health 19:211-220.
68. Hyslop, F., E. D. Palmes, W. C. Alford, A. R. Monaco, and L. T.
Fairhall. 1943. The Toxicity of Beryllium. N.I.H. Bull. No. 181,
Washington, D.C. 56 pp.
69. International Agency for Research on Cancer. 1972. IARC Monographs
on the Evaluation of Carcinogenic Risk of Chemical to Man. Vol. 1.
IARC, Lyon. pp. 17-28.
70. Israel, H. L., and M. Sones. 1959. The Differentiation of Sarcoid-
osis and Beryllium Disease. Arch. Ind. Health 19:160-163.
-------
157
71. Ivanova, A. S. 1970. Changes in the Protein-Carbohydrate Components
of the Pulmonary Connective Tissue in Experimental Berylliosis. Gig.
Tr. Prof. Zabol. 15:32-35.
72. Jacques, A., and H. R. Witschi. 1973. Beryllium Effects on Aryl
Hydrocarbon Hydroxylase in Rat Lung. Arch. Environ. Health 27:
243-247.
73. Jones, J. M., and H. E. Amos. 1974. Contact Sensitivity i-n vitro:
Activation of Actively Allergized Lymphocytes by a Beryllium Complex.
Int. Arch. Allergy 46:161-171.
74. Jones, J. M., and H. E. Amos. 1975. Contact Sensitivity in vitro:
II. The Effect of Beryllium Preparations on the Proliferative Re-
sponses of Specifically Allergised Lymphocytes and Normal Lymphocytes
Stimulated with PHA. Int. Arch. Allergy Appl. Immunol. 48:22-29.
75. Jones-Williams, W., J. Grey, and E. Pioli. 1972. Diagnosis of Beryl-
lium Disease. Br. Med. J. 4:175.
76. Kanarek, D. J., R. A. Wainer, R. I. Chamberlin, A. L. Weber, and
H. Kazemi. 1973. Respiratory Illness in a Population Exposed to
Beryllium. Am. Rev. Respir. Dis. 108:1295-1302.
77. Kelley, W. N., S. E. Goldfinger, and H. L. Hardy. 1969. Hyper-
uricemia in Chronic Beryllium Disease. Ann. Intern. Med. (United
States) 70:977-983.
78. Kharlamova, S. F., and I. N. Potapova. 1968. Beryllium Content in
the Liver and in Its Cellular Fractions in Experiments. Farmakol.
Toksikol. (Moscow) 31:357-359.
79. Klemperer, F. W., A. P. Martin, and R. E. Liddy. 1952. The Fate of
Beryllium Compounds in the Rat. Arch. Biochem. Biophys. 41:148-152.
80. Komitowski, D. 1972. Histochemical Study Into Histogenesis of
Bone Tumors Developing Under the Effect of Beryllium. Chem. Abstr.
76: No. 95364C.
81. Konchalovskaya, N. M., and K. V. Glotova. 1969. Chronic Pulmonary
Heart in Silicosis, Berylliosis and Chronic Dust-Induced Bronchitis.
Klin. Med. (Moscow) 47:16-20.
82. Krivanek, N., and A. L. Reeves. 1972. The Effect of Chemical Forms
of Beryllium on the Production of the Immunologic Response. Am. Ind.
Hyg. Assoc. J. 33:45-52.
83. Krivanek, N., and A. L. Reeves. 1973. Suppression of Delayed Hyper-
sensitivity to Beryllium in Guinea Pigs by Cyclophosphamide. Toxicol.
Appl. Pharmacol. 25:476.
-------
158
84. Kurysheva, N. G. 1969. Incorporation of Lysine-^C and Glycine-lftC
into Soluble and Insoluble Lung Proteins in Experimental Berylliosis.
Gig. Tr. Prof. Zabol. 13(7):51-52.
85. Kuznetsov, A. V., 0. G. Matveev, and G. D. Suntsov. 1974. Differ-
ences in the Distribution of Radioactive Beryllium Chloride with and
without Carrier in Rats during Intratracheal Administration. Gig.
Sanit. 10:113-114.
86. Levy, B. M., and G. M. Higgins. 1965. Reactions Within the Lungs
of Guinea Pigs to the Intratracheal Administration of Zinc Beryllium
Silicate. Am. Ind. Hyg. Assoc. J. 26:227-235.
87. Lieben, J., J. A. Dattoli, and V. M. Vought. 1966. The Significance
of Beryllium Concentrations in Urine. Arch. Environ. Health 12:331-334,
88. Lieben, J., and R. R. Williams. 1969. Respiratory Disease Associ-
ated with Beryllium Refining and Alloy Fabrication. 1968 Follow-up.
J. Occup. Med. 11:480-485.
89. Love, G. J. 1972. Adverse Health Effects of Trace Materials in the
Environment. In: Environmental Chemicals. Human and Animal Health.
August 7-11, 1972, Ft. Collins, Colo. pp. 45-56.
90. Luke, M. Z., L. Hamilton, and T. C. Hollocher. 1975. Beryllium-
Induced Misincorporation by a DNA-Polymerase. Possible Factor in
Beryllium Toxicity. Biochem. Biophys. Res. Commun. (United States)
62:497-501.
91. Mackay, G. R., D. H. Groth, and M. L. Mead. 1970. Light and Elec-
tron Microscopic Studies of Beryllium Hydroxide—Induced Rat Pulmonary
Tumors. Toxicol. Appl. Pharmacol. 17:299.
92. Mainigi, K. D., and E. Bresnick. 1969. Inhibition of Deoxythymidine
Kinase by Beryllium. Biochem. Pharmacol. 18:2003-2007.
93. Mancuso, T. F. 1970. Relation of Duration of Employment and Prior
Respiratory Illness to Respiratory Cancer Among Beryllium Workers.
Environ. Res. 3:251-275.
94. Mancuso, T. F., and A. A. El-Attar. 1969. Epidemiological Study of
the Beryllium Industry. Cohort Methodology and Mortality Studies.
J. Occup. Med. 11:422-434.
95. Marcotte, J., and H. P. Witschi. 1972. Synthesis of RNA and Nuclear
Proteins in Early Regenerating Rat Livers Exposed to Beryllium. Res.
Commun. Chem. Pathol. Pharmacol. 3:97-104.
96. Marx, J. J., Jr., and R. Burrell. 1973. Delayed Hypersensitivity
to Beryllium Compounds. J. Immunol. 111:590-598.
97. Matilla, A., A. Galera, E. Pascual, and R. Carapeto. 1973. Chronic
Berylliosis. Br. J. Dis. Chest 67:308-314.
-------
159
98. Mosser, E. L., and D. A. Clark. 1970. Beryllium Sulfate Effect on
Vascular Volumes. Aerospace Med. 41:640-643.
99. Mukhina, S. T. 1967. Effect of Magnesium on Oxidative Processes in
Rat Liver and Lung Homogenates as a Result of Experimental Beryllium
Intoxication. Unpublished translation of Vliyaniye Magniya na
Protsessy Okisleniya v Gomogenatakh, Pecheni i Legkikh Krys pri
Eksperimental'noy Berilliyevory Intoksiktatsii. Gig. Tr. Prof.
Zabol. 11:43-46.
100. Needham, A. E. 1974. The Effect of Beryllium on the Ultra-violet
Absorbance Spectrum of Nucleic Acids. Int. J. Biochem. (Great
Britain) 5:291-299.
101. Neff, T. A., and T. L. Petty. 1969. Chronic Beryllium Disease.
Rocky Mount. Med. J. 66:52-55.
102. Niemoller, H. K. 1962. Hauttest fur Beryllium nach Curtis und
dessen Modifikationen. Arch. Gewerbepathol. Gewerbehyg. 19:27-34.
103. Niemoller, H. K. 1963. Spatcarcinome durch Berylliumaerosole beim
Menschen (Delayed Carcinoma Induced by Beryllium Aerosol in Man).
Int. Arch. Gewerbepathol. 20:180-186.
104. Nishimura, M. 1966. Clinical and Experimental Studies on Acute
Beryllium Disease. Nagoya J. Med. Sci. 28:17-44.
105. Norris, G. F., and M. C. Peard. 1963. Berylliosis: Report of Two
Cases, with Special Reference to the Patch Test. Br. Med. J.
1:378-383.
106. Orlova, A. A., and K. V. Glotova. 1969. Cardiac Changes in Chronic
Berylliosis (According to Clinico-Electrocardiographic Findings).
Gig. Tr. Prof. Zabol. 13:32-36.
107. Palazzolo, M. J., and A. L. Reeves. 1975. Hypersensitivity to
Beryllium in Guinea Pigs. Toxicol. Appl. Pharmacol. 33:127.
108. Pavlova, I. V., S. F. Kharlamova, and N. G. Kurysheva. 1970. Pro-
tein Metabolism During Experimental Berylliosis. Gig. Tr. Prof.
Zabol. 14:56-57.
109. Petzow, G., and H. Zorn. 1974. Toxikologie von Beryllium-Haltigen
Substanzen (Toxicology of Beryllium-Containing Substances). Chem.
Ztg. 98:236-241.
110. Peyton, M. F., and J. Worcester. 1959. Exposure Data and Epidemi-
ology of the Beryllium Dose Registry — 1958. Arch. Ind. Health
19:94-99.
111. Polak, L., J. M. Barnes, and J. L. Turk. 1968. The Genetic Control
of Contact Sensitivity to Inorganic Metal Compounds in Guinea Pigs.
Immunology 14:707-711.
-------
160
112, Potapova, I. N., and N. I. Seleznev. 1967. Changes of Mitochondrial
Apparatus and of Some Other Delicate Pulmonary Structure Components
in Experimental Berylliosis. Arkh. Patol. (Moscow) 29:15-19.
113. Preuss, 0. P. 1975. Beryllium and Its Compounds. Proceedings of
the Symposium on Toxicity of Metals, June 5-6, 1974, Pittsburgh, Pa.
Industrial Health Foundation, Pittsburgh, pp. 31-43.
114. Pugliese, P. T., C. M. Whitlock, B. Ernst, and R. R. Williams. 1968.
Serological Reactions of Berylliosis Patients to Extracts of Lung
Tissue. Arch. Environ. Health 16:374-379.
115. Redding, R. A., H. L. Hardy, and E. A. Gaensler. 1968. Beryllium
Disease: A 16 Year Follow-up Case Study. Respiration 25:263-278.
116. Reeves, A. L. 1965. The Absorption of Beryllium from the Gastro-
intestinal Tract. Arch. Environ. Health 11:209-214.
117. Reeves, A. L. 1974. Umweltgefahrdung durch Beryllium (Worldwide
Danger from Beryllium). Zentralbl. Arbeitsmed. 24:46-56.
118. Reeves, A. L., D. Deitch, and A. J. Vorwald. 1967. Beryllium Car-
cinogenesis: I. Inhalation Exposure of Rats to Beryllium Sulfate
Aerosol. Cancer Res. 27:439-445.
119. Reeves, A. L., and N. D. Krivanek. 1974. The Influence of Cutaneous
Hypersensitivity to Beryllium on the Development of Experimental Pul-
monary Berylliosis. Trans. N. Y. Acad. Sci. Ser. II, 36(l):78-93.
120. Reeves, A. L., N. D. Krivanek, E. K. Busby, and R. H. Swanborg. 1972.
Immunity to Pulmonary Berylliosis in Guinea Pigs. Int. Arch.
Arbeitsmed. 29:209-220.
121. Reeves, A. L., N. D. Krivanek, and M. J. Palazzolo. 1975. Cutaneous
Hypersensitivity to Beryllium and Pulmonary Berylliosis. Int. Congr.
Occup. Health Abstr. 18:430.
122. Reeves, A. L., R. H. Swanborg, E. K. Busby, and N. D. Krivanek. 1971.
The Role of Immunologic Reactions in Pulmonary Berylliosis. In:
Inhaled Particles III, W. H. Walton, ed. Vol. 2. Unwin Brothers, Ltd.
Surrey, England, pp. 599-608.
123. Reeves, A. L., and A. J. Vorwald. 1961. The Humoral Transport of
Beryllium. J. Occup. Med. 3:567-574.
124. Reeves, A. L., and A. J. Vorwald. 1967. Beryllium Carcinogenesis:
II. Pulmonary Deposition and Clearance of Inhaled Beryllium Sulfate
in the Rat. Cancer Res. 27:446-451.
125. Reiner, E. 1971. Binding of Beryllium to Proteins. In: A Sympo-
sium on Mechanisms of Toxicity, W. N. Aldridge, ed. St. Martin's
Press, New York. pp. 111-125.
-------
161
126. Resnick, H., and W.K.C. Morgan. 1971. Immunoglobulin Levels in
Berylliosis. In: Inhaled Particles III, W. H. Walton, ed. Vol.
II. Unwin Brothers, Ltd. Surrey, England, pp. 589-597.
127. Resnick, H., M. Roche, and W.K.C. Morgan. 1970. Iramunoglobulin
Concentrations in Berylliosis. Am. Rev. Respir. Dis. 101:504-510;
128. Robinson, F. R. 1973. Toxicity of Beryllium and Other Elements
in Missile Propellants. Clin. Toxicol. 6:497-502.
129. Robinson, F. R., F. Schaffner, and E. Trachtenberg. 1968. Ultra-
structure of the Lungs of Dogs Exposed to Beryllium-Containing
Dusts. Arch. Environ. Health 17:193-203.
130. Roschin, A. V. 1971. Industrial Aerosols of Rare Metals and Their
Hygienic Significance. In: Inhaled Particles III, W. H. Walton,
ed. Vol. II. Unwin Brothers, Ltd., Surrey, England, pp. 811-817.
131. Sanders, C. L., and W. C. Cannon. 1975. Pulmonary Clearance and
Pathogenic!ty of Inhaled High-Fired Beryllium Oxide. Carcinogenic
Study with 239Pu02. In: Toxicology of Inhaled Beryllium Compounds.
Pacific Northwest Laboratories Annual Report ]974 USAEC Division
Biomedical Environmental Research Part I. Biomed. Sci. BNWL-1950
Ptl. pp. 49-51.
132. Sanders, C. L., W. C. Cannon, G. J. Powers, and R. R. Adee. 1974.
Toxicology of Inhaled Low-Fired and High-Fired Beryllium Oxides in
the Rat and Hamster. BNWL-1818, Battelle Pacific Northwest Lab.
24 pp.
133. Sanders, C. L., W. C. Cannon, G. J. Powers, R. R. Adee, and D. M.
Meier. 1975. Toxicology of High-Fired Beryllium Oxide Inhaled by
Rodents. Arch. Environ. Health 30:546-551.
134. Sarkar, T. K., E. R. Jones, and V. U. Lutwyche. 1971. The Diagno-
sis of Beryllium Lung Disease. Br. J. Dis. Chest 65:182-195.
135. Schepers, G.W.H. 1961. Neoplasia Experimentally Induced by Beryl-
lium Compounds. In: Progress in Experimental Tumor Research, F.
Homburger, ed. Vol. 2. Hafner Publishing Co., Ind., New York.
pp. 203-244.
136. Schepers, G.W.H. 1964. Biological Action of Beryllium, Reaction
of the Monkey to Inhaled Aerosols. Ind. Med. Surg. 33:1-16.
137. Schneider, M., M. I. Resnick, and K. F. Wellmann. 1973. Increased
Bone Formation in Rabbits Following Intravenous and Intra-Osseous
Injection of Zinc Beryllium Silicate. Clin. Orthop. Relat. Res.
92:251-259.
138. Schroeder, H. A., and M. Mitchener. 1975a. Life-term Studies in
Rats: Effects of Aluminum, Barium, Beryllium, and Tungsten. J.
Nutr. 105(4):421-427.
-------
162
139. Schroeder, H. A., and M. Kitchener. 19752?. Life-term Effects of
Mercury, Methyl Mercury, and Nine Other Trace Metals on Mice. J.
Nutr. 105(4):452-458.
140. Schubert, J., and M. W. Rosenthal. 1959. Chemical Approaches to
the Treatment of Beryllium Poisoning. Arch. Ind. Health 19:169-178.
141. Schubert, J., M. R. White, and A. Lindenbaum. 1952. Studies on
the Mechanism of Protection by Aurintricarboxylic Acid in Beryllium
Poisoning. J. Biol. Chem. 196:279-288.
142. Scott, J. K., W. F. Neuman, and R. Allen. 1950. The Effect of
Added Carrier on the Distribution and Excretion of Soluble Be7.
J. Biol. Chem. 182:291-298.
143. Seeler, A. 0. 1959. Treatment of Chronic Beryllium Poisoning.
Arch. Ind. Health 19:164-168.
144. Silverman, L. 1959. Control of Neighborhood Contamination Near
Beryllium-Using Plants. Arch. Ind. Health 19:254-262.
145. Sirover, M. A., and L. A. Loeb. 1976. Metal-induced Infidelity
During DNA Synthesis. Proc. Nat. Acad. Sci. 73:2331-2335.
146. Spencer, H. C., S. B. McCollister, R. J. Kociba, and C. G. Humiston.
1972. Toxicological Studies on a Beryllium Containing Exhaust Prod-
uct. In: Proceedings of the 3rd Annual Conference on Environmental
Toxicology, October 25-27, 1972. AMRL-TR-72-130, Aerospace Medical
Research Laboratory, Wright-Patterson Mr Force Base, Ohio. pp. 303-
315.
147. Sterner, J. H., and M. Eisenbud. 1951. Epidemiology of Beryllium
Intoxication. Arch. Ind. Hyg. 4:123-151.
148. Stoeckle, J. D., H. L. Hardy, and B. Chang-Wai Ling, 1975. The
Compensation Experience of Patients with Chronic Beryllium Disease.
J. Occup. Med. 17:167-170.
149. Stoeckle, J. D., H. L. Hardy, and A. L. Weber. 1969. Chronic Beryl-
lium Disease, Long-Term Follow-up of Sixty Cases and Selective Review
of the Literature. Am. J. Med. 46:545-561.
150. Stokinger, H. E. 1972. Experimental Toxicology. In: The Toxi-
cology of Beryllium, I. R. Tabershaw, ed. Public Health Service
Publication No. 2173, U.S. Department of Health, Education, and
Welfare, Washington, D.C. pp. 17-32.
151. Stokinger, H. E., G. F. Sprague III, R. H. Hall, N. J. Ashenburg,
J. K. Scott, and L. T. Steadman. 1950. Acute Inhalation Toxicity
of Beryllium. Arch. Ind. Hyg. Occup. Med. 1:379-397.
152. Stokinger, H. E., and C. A. Stroud. 1951. Anemia in Acute Experi-
mental Beryllium Poisoning. J. Lab. Clin. Med. 38:173-182.
-------
163
153. Sumino, K., K. Hayakawa, T. Shibata, and S. Kitamura. 1975. Heavy
Metals in Normal Japanese Tissues. Arch. Environ. Health 30:487-494.
154. Tapp, E. 1966. Beryllium Induced Sarcomas of the Rabbit Tibia.
Br. J. Cancer 20:778-783.
155. Tapp, E. 1969a. Osteogenic Sarcoma in Rabbits Following Subperio-
steal Implantation of Beryllium. Arch. Pathol. 88:89-95.
156. Tapp, E. 19692?. Changes in Rabbit Tibia Due to Direct Implantation
of Beryllium Salts. Arch. Pathol. 88:521-529.
157. Tepper, L. B. 1972a. Beryllium. Critical Reviews in Toxicology.
(CRC Press) 1(3):235-259.
158. Tepper, L. B. 19722?. Beryllium. In: Metallic Contaminants and
Human Health, D.H.K. Lee, ed. Academic Press, New York. pp. 127-137.
159. Tepper, L. B., H. L. Hardy, and R. I. Chamberlin. 1961. Toxicity
of Beryllium Compounds, E. Browning, ed. Elsevier Publishing Co.,
New York. 190 pp.
160. Thomas, M., and W. N. Aldridge. 1966. The Inhibition of Enzymes
by Beryllium. Biochem. J. (Great Britain) 98:94-99.
161. Toda, G. 1968. The Effects of Cations on the Inhibition of Sodium
and Potassium Activated Adenosinetriphosphatase by Beryllium. J.
Biochem. 64:457-464.
162. Toda, G., H. Koide, and Y. Yoshitoshi. 1971. The Effects of Cations
on the Inhibition of K+-Activated Phosphatase by Beryllium. J.
Biochem. 69:73-82.
163. Truhaut, R., B. Festy, and J. Y. LeTalaer. 1968. Modes d'Interaction
de Beryllium avec 1'Acide Deoxyribonucleique et son Effet sur des
Systemes Enzymiques (Modes of Interaction of Beryllium with DNA and
its Effect on Enzyme Systems). C. R. Acad. Sci. Ser. D 266:1192-1195.
164. Turk, J. L., and L. Polak. 1969. Experimental Studies on Metal
Dermatitis in Guinea Pigs. G. Ital. Dermatol. 44:426-430.
165. U.S. Department of Health, Education, and Welfare. 1972. Criteria
for a Recommended Standard. Occupational Exposure to Beryllium.
NIOSH, Washington, D. C. pp. 112.
166. Vacher, J. 1972. Immunological Responses of Guinea-Pigs to Beryl-
lium Salts. J. Med. Microbiol. 5:91-108.
167. Vacher, J., R. Deraedt, and J. Benzoni. 1973. Compared Effects of
Two Beryllium Salts (Soluble and Insoluble): Toxicity and Blockade
of the Reticuloendothelial System. Toxicol. Appl. Pharmacol.
24:497-506.
-------
164
168. Vacher, J., R. Deraedt, and J. Benzoni. 1974. Role of the Reti-
culoendothelial System in the Production of a-Macrofetoprotein in
the Rat Following Intravenous Injection of Beryllium and Other
Particles. Toxicol. Appl. Pharmacol. 28:28-37.
169. Vacher, J., R. Deraedt, and M. Flahaut. 1975. Possible Role of
Lysosomal Enzymes in Some Pharmacological Effects Produced by Beryl-
lium. Toxicol. Appl. Pharmacol. 33:205-213.
170. Vacher, J., and H. B. Stoner. 1968a. The Removal of Injected
Beryllium from the Blood to the Rat. The Role of the Reticulo-
Endothelial System. Br. J. Exp. Pathol. 49:315-323.
171. Vacher, J., and H. B. Stoner. 1968&. The Transport of Beryllium
in Rat Blood. Biochem. Pharmacol. 17:93-107.
172. Van Cleave, C. D., and C. T. Kaylor. 1955. Distribution, Retention,
and Elimination of Be7 in the Rat after Intratracheal Injection.
Arch. Ind. Health 11:375-392.
173. VanOrdstrand, H. S. 1959. Diagnosis of Beryllium Disease. Arch.
Ind. Health 19:157-159.
174. VanOrdstrand, H. S., R. Hughes, J. M. DeNardi, and M. G. Cannody.
1945. Beryllium Poisoning. J. Am. Med. Assoc. 129:1084-1090.
175. Vasil'eva, E. V. 1969. Immunological Assessment of Experimental
Berylliosis. Byull. Eksp. Biol. Med. 3:74-77.
176. Vasil'eva, E. V. 1972. Changes in the Antigenic Composition of
the Lungs in Experimental Berylliosis. Trans, from Byull. Eksp.
Biol. Med. (Bull. Exp. Biol. Med.) (Eng. trans, available from
Consultants Bureau, New York) 73:76-80.
177. Vegni-Talluri, M., and V. Guiggiani. 1967. Action of Beryllium
Ions on Primary Cultures of Swine Cells. Carylogia 20:355-367.
178. Voisin, G. A., A. Collet, J. C. Martin, H. Daniel-Moussard, and
F. Toullet. 1964. Propriete's Immunologiques de Silice et de
Composes due Beryllium: les Formes Solubles Comparees aux Formes
Insolubles (Immunologic Properties of Silica and Beryllium Com-
pounds: Soluble Forms Compared to Insoluble Forms). Rev. Franc.
Et. Clin. Biol. 9:819-828.
179. Vorwald, A. J. 1966. Medical Aspects of Beryllium Disease. In:
Beryllium. Its Industrial Hygiene Aspects, H. E. Stokinger, ed.
Academic Press, New York. pp. 167-200.
180. Vorwald, A. J. 1967. Biological Manifestations of Toxic Inhalants
in Monkeys. Paper presented: Symp. Use Nonhuman Primates Drug
Eval., H. Vagtborg, ed. Univ. of Texas Press, Austin. (Abstract.)
-------
165
181. Vorwald, A. J., and A. L. Reeves. 1959. Pathologic Changes
Induced by Beryllium Compounds. Arch. Ind. Health 19:190-199.
182. Vorwald, A. J., A. L. Reeves, and E.C.J. Urban. 1966. Experimental
Beryllium Toxicology. In: Beryllium. Its Industrial Hygiene
Aspects, H. E. Stokinger, ed. Academic Press, New York. pp. 201-234.
183. Wagner, W. D., D. H. Groth, J. L. Holtz, G. E. Madden, and H. E.
Stokinger. 1969. Comparative Chronic Inhalation Toxicity of Beryl-
lium Ores, Bertrandite and Beryl, with Production of Pulmonary
Tumors of Beryl. Toxicol. Appl. Pharmacol. 15:10-29.
184. White, M. R., A. J. Finkel, and J. Schubert. 1951. Protection
Against Experimental Beryllium Poisoning by Aurintricarboxylic
Acid. J. Pharmacol. Exp. Ther. 102:88-93.
185. Williams, C. R. 1959. Evaluation of Exposure Data in the Beryllium
Registry. Arch. Ind. Health 19:263-267.
186. Williams, W. J. 1971. The Beryllium Granuloma. Proc. R. Soc.
Med. 64:22-24.
187. Williams, W. J., J. H. Lawrie, and H. J. Davies. 1967. Skin Gran-
ulomata Due to Beryllium Oxide. Br. J. Surg. 54:292-297.
188. Witschi, H. 1968. Inhibition of Deoxyribonucleic Acid Synthesis
in Regenerating Rat Liver by Beryllium. Lab. Invest. 19:67-70.
189. Witschi, H. P. 1970. Effects of Beryllium on Deoxyribonucleic
Acid—Synthesizing Enzymes in Regenerating Rat Liver. Biochem. J.
(Great Britain) 120:623-634.
190. Witschi, H. P. 1971. Liver Cell Injury by Beryllium. In: A
Symposium on Mechanisms of Toxicity, W. N. Aldridge, ed. St.
Martin's Press, Inc., New York. pp. 129-145.
191. Witschi, H. P., and W. N. Aldridge. 1967. Biochemical Changes in
Rat Liver After Acute Beryllium Poisoning. Biochem. Pharmacol.
(Great Britain) 16:263-278.
192. Witschi, H. P., and W. N. Aldridge. 1968. Uptake, Distribution
and Binding of Beryllium to Organelles of the Rat Liver Cell.
Biochem J. (Great Britain) 106:811-820.
193. Witschi, H. P., and P. Marchand. 1971. Interference of Beryllium
with Enzyme Induction in Rat Liver. Toxicol. Appl. Pharmacol.
20:565-572.
194. Zelman, I. B., H. Wisniewski, W. Graban, and M. Januszewska. 1967.
Zmiany w Mozgu po Podaniu Berylu (7Be) [Changes in the Central
Nervous System After Injection of Beryllium into the Cerebello-
medullary Cistern and Intraspinally (Studies with Radioactive 7Be)].
Neuropatol. Pol. 3:351-363.
-------
166
195. Zielinski, J. F. 1959. Direct Medical Controls in the Beryllium
Industry. Arch. Ind. Health 19:118-122.
196. Zschunke, E., and H. Folesky. 1969. Experimental-Untersuchungen
iiber Sensibilisierung mit Beryllium (Experimental Investigations on
Sensitization with Beryllium). Hautarzt 20:403-404.
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SECTION 7
ENVIRONMENTAL DISTRIBUTION AND TRANSFORMATION
7.1 SUMMARY
Beryllium and its compounds are widely used in industry, primarily
in electrical applications. There are two American beryllium producers —
Brush-Wellman, Inc., of Elmore, Ohio, and KBI Industries, of Reading,
Pennsylvania. United States demand for beryllium is expected to be 1500
metric tons (1660 tons) in the year 2000; U.S. reserves are estimated at
72,700 metric tons (80,100 tons). About 95% of the beryllium ore used in
the United States is imported, although domestic production is expected
to increase until it accounts for about half the ore consumed.
Beryllium enters the environment principally from coal combustion.
World coals contain 0.1 to 1000 ppm beryllium and estimates indicate that
as much as 84% of this beryllium can be released during combustion. The
second major source of beryllium release is beryllium production, which
accounts for about 4% of all beryllium released. Other sources include
oil combustion, ceramic manufacture, rocket firing, and space vehicle heat
shield evaporation. The two U.S. beryllium production plants, located in
Pennsylvania and Ohio, are the sites of most U.S. emissions.
The beryllium content of common rocks and minerals ranges from less
than 1 ppm to about 10 ppm, while beryllium ores may contain several thou-
sand parts per million. The major ore is beryl, which contains about 5%
beryllium metal. Major U.S. beryllium deposits are found in Kentucky,
Texas, Arizona, Nevada, and Idaho. World soils average 6 ppra beryllium,
with a range of 0.1 to about 40 ppm; U.S. soils average about 1 ppm beryl-
lium or less.
Beryllium is almost nonexistent in natural waters: freshwater aver-
ages less than 0.001 ppm, and seawater contains about 0.0000006 ppm. Beryl-
lium in water is primarily in solution rather than in suspension. Sediments
contain 2 to 3 ppm. Finished U.S. waters average 0.00019 ppm beryllium
and range from 0.00001 to 0.00122 ppm. The recommended provisional limit
for beryllium in water is 1 ppm.
Unpolluted air usually contains less than 0.0001 ug/m3 beryllium.
Urban air generally contains more than rural air. The average daily atmos-
pheric concentration in the United States is less than 0.0005 yg/m3. In
the past, elevated beryllium concentrations have been found in air near
beryllium processing plants, but pollution control equipment is available
and is now employed to meet U.S. air standards (an average of 0.01 ug/m3
beryllium over a 30-day period).
Beryllium chemistry in the soil has not been thoroughly investigated,
but it is thought to be similar to that of aluminum or zinc. The beryl-
lium ion participates in cation exchange reactions and undergoes isomor-
phic substitution in secondary clay minerals. Beryllium is strongly fixed
167
-------
168
in many soils and will displace divalent cations which share common sorp-
tion sites. Residence times for beryllium in soil were not located in
the literature.
The oxide and hydroxide of beryllium are relatively insoluble at the
common pH of natural waters; hence, beryllium does not readily go into
solution during the weathering process. About 9600 metric tons (10,579
tons) beryllium is added to the oceans each year in water and sediments;
approximately 0.00002% of this amount is retained. The residence time
of beryllium in the oceans is on the order of a few hundred years.
Only a small amount of the total beryllium waste produced by indus-
try is composed of actual beryllium scrap. Beryllium users can resell
virtually all scrap to producers. The major portion of beryllium wastes
results from pollution control efforts. It is recommended that wastes
that cannot be recycled be buried in plastic containers sealed in metal
drums. These practices are judged adequate to handle beryllium wastes
now and in the foreseeable future.
Data concerning the beryllium content of food are scarce. An Aus-
tralian study found the beryllium content of foodstuffs to be low, ranging
from 0.01 to 0.10 ppm. Oyster flesh and mushrooms contained the highest
values. Zorn and Diem (1974) measured beryllium concentrations in food
crops and tobacco in Western Germany. They found in polished rice 0.08,
in toasted bread 0.12, in potatoes 0.17, in tomatoes 0.24, and in head
lettuce 0.33 vg beryllium per gram dry substance. In three brands of cig-
arettes, the values were 0.47, 0.68, and 0.74 yg beryllium per cigarette,
with 4.5%, 1.6%, and 10.0% of the beryllium content, respectively, escap-
ing into the smoke during smoking. Beryllium is not known to biomagnify
within the food chain.
7.2 PRODUCTION AND USAGE
Beryllium is used in industry in three main forms: beryllium metal,
beryllium alloys, and beryllium oxide (Table 7.1). Two beryllium pro-
ducers exist in the United States — Brush-Wellman, Inc., of Elmore, Ohio,
and KBI Industries, of Reading, Pennsylvania (Ottinger et al., 1973).
Production is 45.4 to 68 metric tons (50 to 75 tons) of beryllium metal
per year, divided about equally between the two plants (Eilertsen, 1965).
Major uses of beryllium and its compounds are given in Table 7.1.
Approximately 25% of all beryllium is used in switchgear; 30% in computer,
radio, television, and electrical applications; 10% in nuclear applica-
tions; 10% in missiles and space programs; and the remainder in welding
and other applications (Heindl, 1970).
Estimated supply-demand relationships for beryllium in 1968 are given
in Figure 7.1. The forecast median demand for the United States in the
year 2000 (Table 7.2) is 1500 metric tons (1660 tons) (Heindl, 1970). U.S.
beryllium reserves are estimated at 72,667 metric tons (80,100 tons) (Table
7.3). Data concerning beryllium reserves in the rest of the world are
lacking. Heindl (1970) estimates the cobbable beryl reserves of 25 coun-
tries, other than the United States, at 272,160 kg (300,000 tons, 12,000
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169
TABLE 7.1. USES OF BERYLLIUM
Form
Use
Beryllium metal
Beryllium-copper alloy
Beryllium oxide
Nuclear applications
Gyroscopes
Accelerometers
Inertial guidance systems
Rocket propellants
Aircraft brakes
Heat shields for space capsules
Portable x-ray tubes
Optical applications
Turbine rotor blades
Mirrors
Missile systems
Nuclear weapons
Springs
Bellows
Diaphragms
Electrical contacts
Aircraft engine parts
Welding electrodes
Nonsparking tools
Bearings
Precision castings
High-strength, current-carrying springs
Fuse clips
Gears
Spark plugs
High-voltage electrical components
Rocket-combustion-chamber liners
Inertial guidance components
Laser tubes
Electric furnace liners
Microwave windows
Ceramic applications
Source: Adapted from U.S. Environmental Protection Agency,
1973a, Table 2-3, p. 2-3.
tons of beryllium). About 95% of the beryllium ore used in the United
States is imported (Griffitts, 1973). Three-fourths of the imported ore
comes from Brazil, the Republic of South Africa, India, Argentina, and
Mozambique. Domestic production is expected to increase, however, until
it accounts for at least half the ore consumed.
-------
ORNL-DWG 77-4411A
WORLD PRODUCTION
200
GOVERNMENT STOCKPILE BALANCE - 1461
NUCLEAR
APPLICATIONS
(SIC 3443)
32
GUIDED MISSILES
AND SPACE VEHICLES
(SIC 1925)
32
ELECTRICAL MEASURING
INSTRUMENTS
(SIC 36111
41
SWITCHGEAR
(SIC 3613)
WELDING
APPARATUS
(SIC 3623)
36»
ELECTRONIC COMPUTER
EQUIPMENT
(SIC 3S73)
36"
RADIO AND TELEVISION
EQUIPMENT
(SIC 3662)
23s
OTHER
34
Figure 7.1. Supply-demand relationships for beryllium, 1968. Values are in metric tons
of beryllium, e - estimate, b = beryl, a = Be-Cu master alloy, m = metal, SIC = Standard Indus-
trial Classification. Source: Adapted from Heindl, 1970, Figure 1, p. 493.
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171
TABLE 7.2. FORECAST OF BERYLLIUM DEMAND
Forecast range of demand for beryllium
(metric tons)
1968
2000
Total
United States
High
Low
Median
United States
316
1750
1260
1500
Primary
High
Low
Median
Rest of world
High
Low
Median
2QR 158°
298 1130
1350
1200
136 360
770
Source: Modified from Heindl, 1970,- p. 497.
TABLE 7.3.. UNITED STATES RESERVES OF BERYLLIUM
Type of deposit and
grade of ore
Pegmatites
+1 beryl
0.2-1 beryl
0.4 beryl
Nonpegmatites
0.5 BeO
0.5 BeO
Size of Beryllium
individual deposits content
(metric tons) (metric tons)
At least 100 400
At least 100 9,800
37,000
24,000
800
Location
Mostly in New
England and
South Dakota
Mostly in North
Carolina
North Carolina
Bertrandite at
Spor Mountain,
Gold Hill, Utah
Bertrandite and
phenacite in
Nevada
Source: Heindl, 1970, Table 1, p. 492.
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172
7.3 DISTRIBUTION OF BERYLLIUM IN THE ENVIRONMENT
7.3.1 Sources of Pollution
Beryllium enters the environment from a variety of sources (Table 7.4).
The major source is coal combustion. World coals contain 0.1 to 1000 ppm
beryllium (Bowen, 1966). Ruch, Gluskoter, and Shimp (1974) reported an
average of 1.61 ppm in 101 U.S. coals, most of which came from the Illinois
Basin. Colorado coal contains 2.5 ± 0.5 ppm beryllium (Phillips, 1973).
Over 1300 coals were analyzed by Stadnichenko, Zubovic, and Sheffey (1961)
(Table 7.5). The average beryllium in ash was 46 ppm. The highest value
was 62 ppm, found in ash of coal from the Appalachian region. Overall,
beryllium was primarily concentrated in the vitrain coal type.
Much of the beryllium in coal is released to the environment during
combustion. Phillips (1973) calculates that 84% of the beryllium in Colo-
rado coals is lost to the atmosphere upon combustion. The U.S. Environmen-
tal Protection Agency (1971) estimates that 0.26 kg (0.58 Ib) of beryllium
is released for every 907 metric tons (1000 tons) of coal burned. About
133 metric tons (147 tons) of beryllium was emitted in the United States
in 1968 due to coal combustion.
TABLE 7.4. SOURCES OF BERYLLIUM EMISSIONS TO THE ENVIRONMENT
_ Annual emission Percent of this
(metric tons) pollutant
Mica, feldspar mining
Gray iron foundry cupolas
Ceramic coatings
Beryllium alloys and compounds
Beryllium fabrication
Power plant boilers
Pulverized coal
Stoker coal
Cyclone coal
All oil
Industrial boilers
Pulverized coal
Stoker coal
Cyclone coal
All oil
Residential and commercial boilers
Coal
Oil
Negligible
4
Negligible
5
Negligible
78
9
3
2
7
12
2
2
1
7
Negligible
2.77
Negligible
3.64
Negligible
59.62
6.93
2.08
1.39
5.55
9.01
1.39
1.39
0.69
5.55
Total 132 100.01
Source: Adapted from Duncan, Keitz, and Krajeski, 1973, Table V, p. 24.
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173
TABLE 7.5. AVERAGE BERYLLIUM CONTENT OF COAL ASH
Region
Eastern
Interior
Northern Great Plains
Rocky Mountains
Total
Number of
samples
376
586
189
191
1342
Average ash
content
(%)
7.59
7.71
9.83
6.22
7.74
Average beryllium
content of the ash
(ppm)
62
49
27
24
46
Source: Adapted from Stadnichenko, Zubovic, and Sheffey, 1961,
Table 7, p. 285.
Oil combustion also results in beryllium release. Data regarding
the beryllium content of crude and residual oils in the United States are
scarce (U.S. Environmental Protection Agency, 1971). One electric company
reported that oil used in 1968 contained less than 0.1 ppm beryllium. The
U.S. Environmental Protection Agency (1971) estimates that oil used in 1968
contained 0.08 ppm beryllium, providing an emission of 7.3 metric tons (8
tons) of beryllium upon combustion.
Many forms of beryllium are emitted from extraction plants (Table 7.6).
These facilities are required to limit ambient beryllium concentrations to
0.01 vig/m3 and have demonstrated their ability to operate within this limit
(U.S. Environmental Protection Agency, 1973a). Beryllium fabrication pro-
vides an atmospheric release of 4.5 kg (10 Ib) of beryllium for every 907
metric tons (1000 tons) of beryllium processed (U.S. Environmental Protec-
tion Agency, 1971). About 6 kg (13 Ib) of beryllium was emitted by this
process in 1968.
Ceramic plants release some beryllium to the environment. These emis-
sions are almost entirely in the form of dusts, fumes, and mists containing
beryllium oxide (U.S. Environmental Protection Agency, 1973a). About 0.45
kg (1 Ib) of beryllium is released for every ton of beryllium processed in
the manufacture of beryllia ceramics (U.S. Environmental Protection Agency,
1971). Fourteen and one-half metric tons (16 tons) of beryllium was re-
leased to the U.S. atmosphere in 1968 as a result of ceramic manufacture.
Beryllium machining facilities produce a variety of emissions. De-
pending on the machining operation in use, chips, dust, mists, or fumes
may be produced (U.S. Environmental Protection Agency, 1973&). Emissions
from beryllium and beryllium oxide machine shops are generally controlled,
in contrast with"those from Be-Cu alloy machine shops, which use only low-
efficiency filters to retain large chips for recycling.
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174
TABLE 7.6. CHARACTERIZATION OF THE EMISSIONS OF
BERYLLIUM EXTRACTION PLANTS
Extraction plant
operation
Emissions
Control device
Ore crushing
Ore milling
Mulling
Briquetting
Sintering
Briquette crushing
and milling
Slurrying
Thickening
Filtering
Leaching
High-purity beryllium
hydroxide production
Beryllium metal
production
Beryllium oxide
production
Beryllium-copper
alloy production
Beryl ore dust
Beryl ore dust
Beryl ore dust,
Na2SiF6, Na2C03
Briquette dust
Beryl dust, sinter
dust
Briquette dust
Ground sinter
Sinter slurry
Sodium fluoroberyllate
Ammonium persulfate
fume
Be (OH) 2 slurry,
fume
(NH4)2BeFlt slurry,
PbCrOit, CaF2, HF,
Be (OH) 2, BeF2,
NHj+F fume, Mg, Be,
MgF2, BeO acid
fume
BeO furnace fume
and dust, BeO dust
Alloy furnace dust,
Be, Cu, BeO
Dry cyclone, baghouse
Dry cyclone, baghouse
Baghouse
Baghouse
Venturi scrubber
Dry cyclone, baghouse
Baghouse
Scrubber
Scrubber
Scrubber
Scrubber
Packed tower scrubber,
scrubbing tower,
floating bed
scrubber, dry
cyclone, venturi
scrubber, baghouses
Packed tower scrubber,
baghouse, mist
collector
Settling chamber,
cyclone, baghouse
Source: Adapted from U.S. Environmental Protection Agency, 1973a,
Table 3-1, p. 3-12.
Foundry operations that generate beryllium fumes include (1) melt-
ing of ingots, (2) preheating of crucibles that have previously contained
beryllium, (3) transfer of alloy among crucibles, (4) dressing and dross
handling, (5) charging molds with alloys, and (6) finishing operations
(U.S. Environmental Protection Agency, 1973a). Cast iron production re-
sults in particulates that contain about 0.003% beryllium (U.S. Environ-
mental Protection Agency, 1971). The degree of emission control is about
-------
175
25%. Beryllium emission to the U.S. atmosphere due to cast iron produc-
tion is estimated at 3.6 metric tons (4 tons) for the year 1968 (U.S.
Environmental Protection Agency, 1971).
A potential for beryllium emissions exists in the rocket propellant
industry. Potential releases could occur during (1) handling, weighing,
and transferring of beryllium powders to mixers; (2) mixing of ingredi-
ents; (3) casting of propellant into molds; (4) curing or polymerization
of propellant; (5) release of the propellant from molds; and (6) machin-
ing of propellant (U.S. Environmental Protection Agency, 1973a).
Rocket motor testing involving combustion of beryllium-containing
propellants can provide emissions from handling of the fuel, from exhaust
fumes, and from accidental fire or explosion (Durocher, 1969). Gases that
may contain beryllium oxide, beryllium nitrate, beryllium carbide, and
beryllium chloride are produced during testing (Beardall and Eatough,
cited in U.S. Environmental Protection Agency, 1973a, p. 3-26; Frame,
1972). Approximately 30% of the total metallic beryllium originally in
the propellant is thought to be emitted during combustion (Durocher, 1969,
p. 39). Major beryllium emissions from this source are not anticipated
in the future (U.S. Environmental Protection Agency, 1971).
Additional sources of beryllium release (believed not to be very sig-
nificant) are evaporation of heat shields during reentry of space vehicles
and missiles into the atmosphere; incineration of municipal trash or sew-
age (U.S. Environmental Protection Agency, 1971); transportation (U.S.
Environmental Protection Agency, 1973a); laundering of beryllium workers'
garments (Durocher, 1969); use of camping lanterns employing beryllium-
coated mantles (Griggs, 1973); and mining of beryllium ore (U.S. Environ-
mental Protection Agency, 1971).
A total of about 148 metric tons (164 tons) of beryllium was emitted
to the U.S. atmosphere in 1968 (U.S. Environmental Protection Agency, 1971).
The distribution of emissions by state is given in Table 7.7. Pennsylvania
and Ohio account for 25% of the total, due to the beryllium production
plants in those states.
7.3.2 Distribution in Rocks and Soils
The beryllium content of rocks and minerals is given in Table 7.8.
According to Bowen (1966), igneous rocks average 2.8 ppm beryllium, shales
about 3 ppm, and sandstones and limestones less than 1 ppm. Representative
beryllium minerals are listed in Table 7.9. All but a small percentage of
beryllium is in common rock-forming minerals rather than beryllium-rich min-
erals (Griffitts, 1973). The main beryllium ore is beryl, which contains
about 5% beryllium metal (Heindl, 1970). Major beryllium deposits may be
found in Kentucky, Texas, Arizona, Nevada, and Idaho (Figure 7.2).
Due to its prevalence in rocks, beryllium occurs in most soils. World
soils average 6 ppm beryllium, with a range of 0.1 to 40 ppm (Bowen, 1966;
Swaine, 1955). Mineral soils contain 0.2 to 10 ppm (Murrmann and Koutz,
1972). Shacklette et.al. (1971) report an average of 1 ppm and a range
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176
TABLE 7.7. BERYLLIUM EMISSIONS BY STATE, 1968
Beryllium emissions
(metric tons)
Pennsylvania and Ohio 37
Illinois 11
Indiana 11
Michigan 10
New York 6
Alabama and Mississippi 6
West Virginia 6
Kentucky 5
North Carolina 5
Tennessee 5
Wisconsin 4
Delaware and Maryland 4
Virginia 4
Georgia and Florida 4
All other states 22
Undistributed 9
Total 149
Source: Adapted from U.S. Environmental
Protection Agency, 1971, p. 3.
of 1 to 7 ppm beryllium in surficial materials of the conterminous United
States (Figure 7.3). Cholak (1959) found 0.13 to 0.88 ppm (an average of
0.37 ppm) in 15 soil samples from Ohio, West Virginia, Georgia, Maryland,
North Carolina, and South Carolina. Soils from Kenya, Africa, contain 0.04
to 1.45 ppm beryllium (Chamberlain, 1959). Kenyan soils high in cobalt
were usually low in beryllium, and vice versa. Soils high in beryllium
usually came from areas of impeded drainage or areas receiving only slight
weathering.
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177
TABLE 7.8. BERYLLIUM IN ROCKS AND MINERALS
Rock type or mineral
Beryllium
content
(ppm)
Igneous
Ultrabasic
Basalt
Nepheline syenite
Diorites
Diorite and gabbro-diorite
Granite
Shales
Shale and clay
Earth's crust
Upper part of the lithosphere
Talc
Asbestos
Kaolin
Monazite
Phosphate
Mafic
Silicic
Alkalic
Meteorites
6
0.2
0.3
0.65
1.6
1.8
3.6
3.6
7
10
2
0.065
0.24
7.4
0.059
0.08 to 3.75
Less than 1
6.5
11.4
0.038
Source: Adapted from Stadnichneko, Zubovic,
and Sheffey, 1961 and Meehan and Smythe, 1967,
Table 1, p. 256. Data collected from several
sources.
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178
TABLE 7.9. REPRESENTATIVE BERYLLIUM MINERALS
Mineral
Beryl
Beryllonite
Bertrandite
Bromellite
Chrysoberyl
Euclase
Hambergite
Helvite
Herderite
Leucophanlte
Phenacite
Composition
3BeO-Al?03-6SiOj
NaBePO^
BeuSi207(OH)r
BeO
Be(A102),
BeHAlSiOt
Be?(OH)B03
Kn..Be3Si30,2S
CsBePfMOH.F)
(Ca,Na)?BeSl2(0,OH,F)
Be2SiOu
Geological
occurrence
Pegmatite
Pegmatite
Pegmatite
Veins
Pegmatite
Pegmatite
Pegmatite
Pegmatite,
veins
Pegmatite
Pegmatite
Pegmatite
Geographical distribution
Widely distributed
Maine
Colorado, Maine, France,
Bohemia
Sweden
Brazil, Ceylon, I'r.ils,
New York
Brazil, Urals, Austrian
Alps
Norway, Madagascar
Iron Mountain, New
Mexico; Norway; Russia;
Australia; Canada;
Brazil
Maine
Norway
Colorado, Urals,
Vosges Mountains
Source: Ad.iptcd fron Krejci and Scheel, 1966, Table
mission of the publisher.
4.1, p. 47. Reprinted by per-
ORNL owo 77 4510
r\
—T~ .::::•»
/ : V
Figure 7.2. Areas of the conterminous United States in which beryl-
lium deposits are most likely to be found. Source: Griffitts, 1978,
Figure 12, p. 92.
-------
128* 124* 120*
H2° «08° 104* tOO* 96* 92* 88° 84* 8O* 76*
ORNL-OWG 7 7-556 J
72* 68' 64«
46'
42-
38°
34°
30°
26°
22°
.... • •.
' * * A
W** ..-*4*4-44 •-- «i
. ^—-*•- -/*
-. -I -
S
500
I I I I I
MILES
H8"
(10°
106°
(02°
98'
94*
go-
82°
78"
46°
:
38*
34«
30°
26'
22*
.
Figure 7.3. Beryllium content of surficial materials of the United States. Source:
Shacklette et al., 1971, Figure 4, pp. D16-D17.
.
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180
Little information is available concerning beryllium distribution
within the soil profile. Indiana losses average 6 ppm beryllium at a depth
of 0.3 to 1.3 ft, 5 ppm at 1.3 to 8.8 ft, and 8 ppm at 8.8 to 17.3 ft
(Leininger, 1957). Mitchell (1957) analyzed a single profile and found a
decrease in beryllium content with an increase in depth. Chamberlain (1959)
reported that beryllium content increased or remained stable with increased
depth in seven profiles. The amount of weathering that has occurred and
the type of parent material present may explain the differences in beryl-
lium content with depth.
7.3.3 Distribution in Water and Sediments
Beryllium is almost nonexistent in natural waters (Committee on Water
Quality Criteria, 1972). Bowen (1966) gave values of less than 0.001 ppm
beryllium in fresh water and 0.0000006 ppm in seawater. Merrill et al.
(1960) determined the average beryllium content of the Pacific Ocean to be
5.7 x 10~7 ppm. Of this, 68% was in solution and 32% in particulate form.
Sediments averaged 2 to 3 ppm. According to Silker et al. (1968), the
average activity of 7Be in the Atlantic Ocean is 329 disintegrations per
minute per 1000 liters. The particulate fraction averaged 20 disintegra-
tions per minute per 1000 liters. Values for the beryllium content of
Australian waters are listed in Table 7.10.
TABLE 7. 10. BERYLLIUM IN AUSTRALIAN WATERS
Water
(ppb)
Mean
Numb" of
samples
Rain
All samples
Lucas Heights
Non-Lucas Heights
River
Lachlan (Forbes)
Macquarie (Bathurst)
Nepean (Emu Plains)
Woronora (Discharge Ft.)
Woronora (Tolofin)
Sea
Pacific Ocean
Indian Ocean
Tank*
Lucas Heights area
0.01 to 0.18 0.07
0.01 to 0.07 0.05
0.03 to 0.18 0.08
0.01
0.01
0.01 to 0.12
0.01 to 0.08
0.002
N.D.
0.03
0.02
0.002
'0.001
0.002
20
5
15
1
1
1
27
26
I
1
Q
N.D. — not detected.
Rainwater collected in tank. This value is lower than
that for rainwater due to sediment settling out.
Source: Adapted from Meehan and Smythe, 1967, Table II,
p. 843. Reprinted by permission of the publisher.
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181
Analysis of over 1500 U.S. raw and finished waters revealed an average
beryllium content of 0.19 yg/liter and a range of 0.01 to 1.22 yg/liter
(Kopp and Kroner, 1968). The maximum concentration which occurred in the
Monongahela River at Pittsburgh was thought to result from mine drainage
in that area. The Atchafalaya River in Louisiana contains 0.1 to 1 ppb
beryllium (Livingstone, 1963); the Delaware and Hudson rivers contain about
10 u ppm (Merrill et al., 1960). The recommended provisional limit for
beryllium in water is 1 ppm (Ottinger et al., 1973).
7.3.4 Distribution in Air
Beryllium is generally found in the atmosphere in minute concentra-
tions. The beryllium content of the atmosphere is less than 0.0001 yg/m3
(Bowen, 1966). Beryllium was undetectable in most of the over 100 cities
sampled by the National Air Surveillance Network (U.S. Department of Health,
Education, and Welfare, 1966; U.S. Environmental Protection Agency, 1973fr).
Chambers et al. (1955, cited in Durocher, 1969, p. 41) found a maximum of
0.003 yg/m3 of beryllium in the air of more than 30 metropolitan areas.
The variation in beryllium -concentration between these urban areas and some
rural areas is shown in Table 7.11. The authors acknowledged limitations
in this study, including locations selected, extent of coverage, methods
used, and inherent defects in analysis of data based on particulate samples.
Despite such limitations, the data are useful for comparative purposes.
Tabor and Warren (1958) found 0.003 yg/m3 of beryllium in suspended par-
ticulate samples from Houston, Denver, and Louisville. Trace quantities
(less than 0.003 yg/m3) were found in Chattanooga, Chicago, Cincinnati,
East Chicago, Minneapolis, Paulsboro, New Orleans, New York, Philadelphia,
and Washington.
Atmospheric beryllium concentrations are often higher than normal near
beryllium processing plants. Sussman, Lieben, and Cleland (1959) reported
a mean concentration of 0.0155 yg/m3 and a maximum concentration of 0.0827
yg/m3 near a Pennsylvania plant. In comparison, background samples from
different areas averaged 0.0002 yg/m3. During a partial plant shutdown
the beryllium concentration averaged 0.0047 yg/m3; a complete two-week
shutdown resulted in an average of 0.0015 yg/m3. Similar results were
reported by Watts, Walsh, and Vought (1959) and by the U.S. Environmental
Protection Agency (1973a).
As expected, the atmospheric concentration of beryllium decreases with
distance from the emission source. Eisenbud et al. (1949) studied this
relationship and found that beryllium ranged from 0.2 yg/m3 at 1/4 mile
from the stack to nil (limit of detection, 0.001 yg/m3) at 10 miles (Fig-
ure 7.4). Data were collected continuously for ten weeks at 350, 420,
650, and 750 ft from the stack. The average beryllium concentrations were
0.15, 0.1, 0.05, and 0.05 yg/m3, respectively. A decrease in beryllium
content with increased distance from the stack is also reported by Watts,
Walsh, and Vought (1959) and by Sussman, Lieben, and Cleland (1959).
The recommended national emission standard for beryllium discharge
is as follows: (1) the total beryllium emission shall not exceed 10 g
of beryllium in a 24-hr period and (2) the total emission shall not exceed
amounts which will result in an out-plant concentration of 0.01 ug/m3
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182
TABLE 7.11. AVERAGE BERYLLIUM CONCENTRATIONS IN
URBAN AND RURAL AREAS
Area
Concentration
(yg/m3)
Cities over 2,000,000
Los Angeles 0.0001
Detroit 0.0004
Philadelphia 0.0005
Chicago 0.0002
New York 0.0003
Cities between 500,000 and 2,000,000
Cincinnati 0.0002
Kansas City 0.0003
Portland . 0.0003
Atlanta 0.0002
Houston 0.0002
San Francisco 0.0001
Minneapolis 0.0002
Rural or suburban
Boonsboro, Maryland 0.0001
Salt Lake City 0.0001
Atlanta 0.0002
Cincinnati 0.0001
Portland 0.0001
Source: Adapted from Chambers et al., 1955 (cited in
Durocher, 1969, p. 42), Table 10, p. 42.
averaged over a 30-day period (Utidjian, 1973). Pollution control devices
to limit beryllium discharge are available (Table 7.12) and are used on an
industry-wide basis to meet the above standard (Ottinger et al., 1973).
As a result, the overall beryllium concentration in the U.S. atmosphere
does not appear to present a health hazard.
Beryllium participates in cation exchange reactions and undergoes
isomorphic substitution in secondary clay minerals (Romney and Childress,
1965). The beryllium ion is strongly fixed in some soils and will displace
divalent cations which share common sorption sites. Under batch equilib-
rium conditions, however, magnesium, barium, and calcium will effectively
-------
183
ORNL-OWG 77-4620
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or
LJ
CD
U.
0
z
g
5;
UJ
o
\
o
\
s
\
s
\
\
V
i
\
N
>
s
\
1
s
s
"
\
\
\
\
.1 0.5 1 5 10
DISTANCE DOWNWIND FROM STACK (miles)
Figure 7.4. Falloff of ground beryllium concentration with distance
away from a beryllium production plant. Source: Adapted from Eisenbud
et al., 1949, Figure 1, p. 284. Reprinted by permission of the publisher.
TABLE 7.12. RECOMMENDED CLEANERS FOR BERYLLIUM HANDLING OPERATIONS
Operation or process phase
Type of cleaner
Estimated
loading
(g/m")
Expected
efficiency
by weight (%)
Ore handling, crushing ball milling, etc. Reverse-jet or shaking bag filter 0.2-57
Sinter furnace
Leaching and hydroxide filter
Sodium fluoride handling (NoBe)
fjcrylHum hydrnxidt- drvi-r
Beryllium hydroxide dryer and calciner
Wet cell or spray scrubber
Same
Same
0.2
0.02
1.1
Beryllium fluoride mixer
Beryllium fluoride furnace
Reduction furnace
Ball mill
Magnetic separator
Pickling
Leach tank
Machining, powder metals handling
Welding, heat treating
Miscellaneous laboratory hoods
Reverse-jet or shaking bag filter 2.3
Wet spray unit for cooling, then 1.6
to above unit
Wet cell or spray tower 0.02
Venturi or orifice scrubber or 11.4
packed tower and wet Cottrell
uni t
Same 2. 3
Wet cell washer 0.02
Small cyclone units plus bag 0.2-2.3
filter with asbestos filter
aid
Bag filter with filter aid and 0.2-2.3
dilution air to bring tempera-
ture to • 180 °F
Roughing filter plus high- 0.002-0.02
efficiency AEC-type filter
80
-•••
99^
99
95"
95'
80
99.9
99.95
^Estimated for single-stage cleaning to be followed by overall final bag collector with asbestos
floats filter aid.
Source: Adapted from Silverann. 1959, Table 4, p. 258. Reprinted by permission of the publisher.
-------
184
compete with beryllium for adsorption sites in soils but not bentonite.
Kaolinite adsorbs beryllium less strongly than soils; in this medium, there-
fore, beryllium can be displaced by the above cations. Residence times for
beryllium in the soil were not located in the literature.
7.4 ENVIRONMENTAL FATE
7.4.1 Mobility and Persistence in Soils
Beryllium chemistry in the soil solution has not been thoroughly inves-
tigated (Murrmann and Koutz, 1972), but it is probably similar to that of
aluminum or zinc (Bohn, 1972; Romney and Childress, 1965). Reactions of
beryllium in nutrient solution and soil are responsive to pH. At low pH,
Be2+ and Be3(OH)33+ are present; at higher pH, precipitates of Be(OH)2 are
formed. With further pH increase, (Be02)2~ should appear (Mesmer and Baes,
1967; Murrmann and Koutz, 1972) (Section 2.2.1.2).
7.4.2 Mobility and Persistence in Water
Beryllium is found in natural waters only in small amounts due to the
low solubility of its oxide and hydroxide at the common pH of such waters
(Kopp and Kroner, 1968). The chloride and nitrate of beryllium are highly
soluble in water, the sulfate is moderately soluble, and the carbonate is
nearly insoluble in cold water (Committee on Water Quality Criteria, 1972).
Beryllium does not go into solution to an appreciable degree during
the weathering process. About 9600 metric tons (10,579 tons) of beryllium
are added to the oceans each year in water and sediments (Schroeder, 1974);
approximately 0.00002% of this amount is retained. Merrill et al. (I960)
have calculated the residence time of beryllium in seawater to be 150 years.
Using the same equation but different numerical values from Arnold (1958),
a residence time of 570 years was determined. Thus, both methods indicate
a beryllium residence time in seawater of a few hundred years.
7.4.3 Mobility and Persistence in Air
Residence times for beryllium in the atmosphere were not located in
the literature. Beryllium in the atmosphere probably returns to earth as
dry fall or in precipitation.
7.5 WASTE MANAGEMENT
Only a small amount of the total beryllium waste produced is composed
of beryllium scrap. This is because beryllium users can resell virtually
all scrap to the producers at $10 to $20 per pound of contained beryllium
(Ottinger et al., 1973). The major portion of beryllium waste results
from pollution control efforts. These wastes are in the form of either
solid particulates or a dilute aqueous solution (e.g., scrubber liquor).
The most desirable method of handling beryllium wastes is recycling
them to producers, a situation that is expected to continue (Ottinger et
al., 1973). For wastes not recycled, burial is recommended. The wastes
-------
185
can first be burned to produce the chemically inert beryllium oxide, pro-
vided the exhaust gases are scrubbed to remove particulates. Both burned
and unburned wastes are preferably placed in plastic containers and sealed
in metal drums prior to burial (U.S. Environmental Protection Agency,
1973a). These practices are deemed adequate to handle beryllium wastes
now and in the foreseeable future.
7.6 BERYLLIUM IN FOODS
Data concerning the beryllium content of foods are scarce. The re-
sults of Meehan and Smythe (1967) are presented in Table 7.13. The samples
they studied were collected in New South Wales, Australia. Values for
foodstuffs were generally low and ranged from 0.01 to 0.10 ppm. Oyster
flesh and mushrooms contained the highest values. The results of Zorn
and Diem (1974), obtained in West Germany, are shown in Tables 7.14 and
7.15. It seems, from these results, that beryllium content of crops in
Europe is appreciably higher than in Australia.
7.7 BIOMAGNIFICATION IN FOOD CHAINS
Beryllium does not biomagnify within food chains. Beryllium ingested
by higher animals is not absorbed through the digestive tract but is read-
ily excreted (Section 6.2). Thus, human consumption of animals that have
ingested beryllium presents no health hazard under normal circumstances.
TABLE 7.13. BERYLLIUM IN AUSTRALIAN FOODS
Survey figures
Sample
Foodstuffs
Beans (Lucas Heights area)
Cabbage (Lucas Heights area)
Hen eggs
Yolk
Yolk plus whites
Shells
Milk
All samples
Lucas Heights area
Hawkesbury and Campbelltown
Mushrooms
Lucas Heights area
Nuts
Peanut kernels
Peanut shells
Almond kernels
Almond shells
Tomatoes (Lucas Heights area)
Yeast (bakers)
Marine
Crabs
Woronora River
Non-Woronora River
Eels
Whole fish
Woronora River
Mullet
Blackfish
Non-Woronora River, mullet
Beryllium level (ppm in ash)
Range Average
N.D.a to 0.01 0.01
0.03
0.01
0.006
0.01A
N.D. to 0.09 0.02
N.D. to 0.04 0.02
N.D. to 0.09 0.02
0.12
0.01 to 0.03 0.02
0.41 to 0.52 0.47
0.01
0.01
0.02
0.02
0.07 to 0.13 0.10
0.17
N.D.
0.03 to 0.36 0.21
0.08 to 0.39 0.23
0.01
Ash fresh
weight (%)
0.65
0.78
1.75
1.01
77.44
0.83
0.81
0.86
1.32
2.6
2.5
2.9
2.9
1.05
1.62
15.4
15.4
5.0
5.2
4.6
Number of
samples
3
1
1
1
1
50
17
33
1
2
2
1
1
1
1
6
1
1
8
4
1
(continued)
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186
TABLE 7.13. (continued)
Sample
Fish gut
Woronora River
Mullet
Blackfish
Leather jacket
Non-Woronora River
Mullet
Blackfish
Fish fillets
Woronora River
Mullet
Blackfish
Perch and bream
Non-Woronora River
Blackfish
Bonita
Perch
Red fin
Mullet
Homos ira Banks 11
Bubble weed (coast south of Sydney)
Catostylus mosaicus (jelly blubber)
Oyster flesh
All samples
Woronora River
Hawkesbury River
Oyster liquid
All samples
Woronora River
Hawkesbury River
Oyster shells
All samples
Woronora River
Hawkesbury River
Plankton preparations
Prawns (green)
Cunjevoi flesh, Pyura stolonifera
Mixture from Cronulla and Coalcliff
Cronulla
Coalcliff
Cunjevoi tunics, Pyura stolonifera
. Mixture from Cronulla and Coalcliff
Cronulla
Coalcliff
River solid particles
Woronora (Discharge Point)
Woronora (Tolofin)
Rockveeds (algae)
Cronulla
Coalcliff
Scallops, Tasmanian
Seaweed, Woronora River
Shellfish flesh
Mixture from Cronulla and Coalcliff
Cronulla
Coalcliff
Shellfish shells
Cronulla
Coalcliff
Starfish, whole, Coalcliff
Zoster a
All samples
Woronora River
Hawkesbury River
Beryllium level
Range
0.42 to 0.71
0.46 to 1.78
0.48 to 0.63
0.04 to 1.33
0.80 to 1.25
N.D. to 0.07
0.01
0.01 to 0.05
0.01 to 0.27
0.02 to 0.14
0.01 to 0.27
0.01 to 0.03
0.01 to 0.03
0.01 to 0.08
0.01 to 0.08
0.02 to 0.06
0.10 to 0.26
0.05 to 0.08
0.02 to 0.54
0.29 to 1.02
0.07 to 0.09
0.30 to 1.15
N.D. to 0.01
N.D. to 0.01
0.28 to 1.12
0.28 to 1.12
Survey
(ppm in ash)
Average
0.54
0.99
0.56
0.43
1.03
0.04
0.01
N.D.
0.01
0.01
0.01
0.01
0.02
0.03
N.D.
0.03
0.03
0.10
0.02
0.02
0.02
0.04
0.04
0.04
N.D.
0.03
0.53
0.18
0.42
0.30
0.07
0.26
N.D.
N.D.
0.01
0.28
0.02
0.66
0.04
0.08
0.73
0.01
0.01
0.02
0.60
0.61
0.41
figures
Ash fresh
weight (%)
9.2
5.6
3.2
4.2
5.7
3.7
3.6
3.7
4.4
2.4
1.6
5.7
3.3
16.5
1.2
2.0
2.0
2.0
2.7
2.5
2.9
94.9
93.8
96.5
13.5
3.5
3.6
9.1
4.1
35.4
38.5
33
4.2
5.2
1.7
5.5
8.8
8.1
14.0
96.4
96.3
37.1
5.5
5.5
5.5
Number of
samples
6
5
2
4
2
2
1
1
2
1
1
1
1
5
1
59
41
18
2
2
1
20
14
6
1
1
1
2
1
1
2
1
1
1
1
2
1
3
1
2
2
2
2
1
28
27
1
N.D. — nondetectable.
Source: Adapted from Meehan and Smythe, 1967, Table II, pp.
of the publisher.
841-843. Reprinted by permission
-------
187
TABLE 7.14. BERYLLIUM IN WEST GERMAN
FOOD CROPS
Crop Be/g
substance
Toasted bread ("knackebrot") 0.12
Green head lettuce 0.33
Tomatoes 0.24
Rice, polished 0.08
Potatoes 0.17
Source: Adapted from Zorn and Diem,
1974, Table 1, p. 5. Reprinted by permis-
sion of the publisher.
TABLE 7.15. BERYLLIUM IN WEST GERMAN
CIGARETTES
Be/cigarette Be/cigarette
in tobacco in smoke
Brand A
Brand B
Brand C
0.74
0.68
0.47
0.074
0.011
0.021
Source: Adapted from Zorn and
Diem, 1974, Table 2, p. 5. Reprinted
by permission of the publisher.
-------
188
SECTION 7
REFERENCES
1. Arnold, J. R. 1958. Trace Elements and Transport Rates in the Ocean.
In: Proceedings of the Second United Nations International Conference
on the Peaceful Uses of Atomic Energy, Vol. 18. United Nations, Geneva.
pp. 344-346.
2. Bohn, H. L. 1972. Soil Absorption of Air Pollutants. J. Environ.
Qual. 1:372-377.
3. Bowen, H.J.M. 1966. Trace Elements in Biochemistry. Academic Press,
New York. pp. 176-177.
4. Chamberlain, G. T. 1959. Trace Elements in Some East African Soils
and Plants: I. Cobalt, Beryllium, Lead, Nickel, and Zinc. East Afr.
Agric. J. 25:121-125.
5. Cholak, J. 1959. The Analysis of Traces of Beryllium. Arch. Ind.
Health 19:123-128.
6. Committee on Water Quality Criteria. 1972. Water Quality Criteria,
1972. National Academy of Sciences, Washington, D.C. p. 244.
7. Duncan, L. J., E. L. Keitz, and E. P. Krajeski. 1973. Selected Char-
acteristics of Hazardous Pollutant Emissions. MTR-6401, Vol. IT. The
MITRE Corporation, Washington, D.C. p. 24.
8. Durocher, N. L. 1969. Preliminary Air Pollution Survey of Beryllium
and Its Compounds. A Literature Review. National Air Pollution Con-
trol Administration Publication No. APTD 69-29, Raleigh, N.C. 79 pp.
9. Eilertsen, D. E. 1965. Beryllium. In: Mineral Facts and Problems.
U.S. Bureau of Mines Bulletin 630, U.S. Government Printing Office,
Washington, D.C. pp. 101-109.
10. Eisenbud, M., R. C. Wanta, C. Dustan, L. T. Steadman, W. B. Harris,
and B. S. Wolf. 1949. Non-Occupational Berylliosis. J. Ind. Hyg.
Toxicol. 31:282-294.
11. Frame, G. M. 1972. Determination of Trace Levels of Beryllium Oxide
in Biological Media. In: Proceedings of the 3rd Annual Conference on
Environmental Toxicology, October 25-27, 1972. AMRL-TR-72-130, Aero-
space Medical Research Laboratory, Wright-Patterson Air Force Base,
Ohio. pp. 319-329.
12. Griffitts, W. R. 1973. Beryllium. In: United States Mineral
Resources, D. A. Brobst and W. P. Pratt, eds. Geological Survey
Professional Paper 820, U.S. Government Printing Office, Washington,
D.C. pp. 85-93.
-------
189
13. Griggs, K. 1973. Toxic Metal Fumes from Mantle-Type Camp Lanterns.
Science 181: 842-843.
14. Heindl, R. A. 1970. Beryllium. In: Mineral Facts and Problems.
U.S. Bureau of Mines Bulletin 650, U.S. Government Printing Office,
Washington, D.C. pp. 489-501.
15. Kopp, J. F., and R. C. Kroner. 1968. Trace Metals in Waters of the
United States. Federal Water Pollution Control Administration, Cin-
cinnati, Ohio. pp. 8, 14, 22.
16. Krejci, L. E., and L. D. Scheel. 1966. The Chemistry of Beryllium.
In: Beryllium. Its Industrial Hygiene Aspects, H. E. Stokinger, ed.
Academic Press, New York. pp. 45-51.
17. Leininger, R. K. 1957. Chemical Differentiation of a Weathered Loess
from a Weathered Till. Soil Sci. 83:43-50.
18. Livingstone, D. A. 1963. Chemical Composition of Rivers and Lakes.
In: Data of Geochemistry, 6th ed., M. Fleischer, ed. Geological
Survey Professional Paper 440-G, U.S. Government Printing Office,
Washington, D.C. p. G-44.
19. Meehan, W. R., and L. E. Smythe. 1967. Occurrence of Beryllium as
a Trace Element in Environmental Materials. Environ. Sci. Technol.
1:839-844.
20. Merrill, J. R., E.F.X. Lyden, M. Honda, and J. R. Arnold. 1960.
The Sedimentary Geochemistry of the Beryllium Isotopes. Geochim.
Cosmochim. Acta 18:108-129.
21. Mesmer, R. E., and C. F. Baes, Jr. 1967. The Hydrolysis of Beryl-
lium (II) in 1 M NaCl. Inorg. Chem. 6:1951-1960.
22. Mitchell, R. L. 1957. Spectrochemical Methods in Soil Investiga-
tions. Soil Sci. 83:1-13.
23. Murrmann, R. P., and F. R. Koutz. 1972. Role of Soil Chemical Proc-
esses in Reclamation of Wastewater Applied to Land. In: Wastewater
Management by Disposal on the Land, S. C. Reed, coordinator. U.S.
Army Cold Regions Research and Engineering Laboratory, Hanover, New
Hampshire, pp. 48-76.
24. Ottinger, R. S., J. L. Blumenthal, D. F. Dal Porto, G. I. Gruber, M. J.
Santy, and C. C. Shih. 1973. Recommended Methods of Reduction, Neu-
tralization, Recovery, or Disposal of Hazardous Waste, Vol. XII. EPA
Report No. EPA-670/2-73-053-1, U.S. Environmental Protection Agency,
Cincinnati, Ohio. pp. 243-258.
25. Phillips, M. A. 1973. Investigations into Levels of Both Airborne
Beryllium and Beryllium in Coal at the Hayden Power Plant Near Hayden,
Colorado. Environ. Lett. 5:183-188.
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190
26. Romney, E. M., and J. D. Childress. 1965. Effects of Beryllium in
Plants and Soil. Soil Sci. 100:210-217.
27. Ruch, R. R., H. J. Gluskoter, and N. F. Shimp. 1974. Occurrence and
Distribution of Potentially Volatile Trace Elements in Coal. EPA
Report No. EPA-650/2-74-054, Research Triangle Park, N.C. pp. 18, 19.
28. Schroeder, H. A. 1974. The Poisons Around Us. Toxic Metals in Food,
Air, and Water. Indiana University Press, Bloomington, Ind. p. 30.
29. Shacklette, H. T., J. C. Hamilton, J. G. Boerngen, and J. M. Bowles.
1971. Elemental Composition of Surficial Materials in the Conter-
minous United States. Geological Survey Professional Paper 574-D,
U.S. Government Printing Office, Washington, D.C. pp. D3-D17.
30. Silker, W. B., D. E. Robertson, H. G. Rieck, Jr., R. W. Perkins,
and J. M. Prospero. 1968. Beryllium-7 in Ocean Water. Science
161:879-880.
31. Silverman, L. 1959. Control of Neighborhood Contamination Near
Beryllium-Using Plants. Arch. Ind. Health 19:172-180.
32. Stadnichenko, T., P. Zubovic, and N. B. Sheffey. 1961. Beryllium
Content of American Coals. Geological Survey Bulletin 1084-K, U.S.
Government Printing Office, Washington, D.C. 295 pp.
33. Sussman, V. H., J. Lieben, and J. G. Cleland. 1959. An Air Pollu-
tion Study of a Community Surrounding a Beryllium Plant. Am. Ind.
Hyg. Assoc. J. 20:504-508.
34. Swaine, D. J. 1955. The Trace-Element Content of Soils. Technical
Communication No. 48, Commonwealth Bureau of Soil Science, Rothamsted
Experimental Station, Harpenden, Commonwealth Agricultural Bureaux,
England. p. 19.
35. Tabor, E. C., and W. V. Warren. 1958. Distribution of Certain Metals
in the Atmosphere of Some American Cities. Arch. Ind. Health 17:145-151.
36. U.S. Department of Health, Education, and Welfare. 1966. Air Quality
Data from the National Air Sampling Networks and Contributing State
and Local Networks, 1964-1965. Division of Air Pollution, Cincinnati,
Ohio. pp. 64-66.
37. U.S. Environmental Protection Agency. 1971'. National Inventory of
Sources and Emissions: Beryllium — 1968. EPA Report No. APTD-1508,
Office of Air and Water Programs, Research Triangle Park, N.C. 53 pp.
38. U.S. Environmental Protection Agency. 1973a. Control Techniques for
Beryllium Air Pollutants. EPA Publication AP-116, U.S. Government
Printing Office, Washington, D.C.
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191
39. U.S. Environmental Protection Agency. 1973Z?. Air Quality Data for
Metals. 1968 and 1969. Office of Air and Water Programs, Research
Triangle Park, N.C. pp. 3-1 to 3-13.
40. Utidjian, H.M.D. 1973. Criteria for a Recommended Standard...
Occupational Exposure to Beryllium and Its Compounds: I. Recommenda-
tions for a Beryllium Standard. J. Occup. Med. 15:659-665.
41. Watts, S. R., F. X. Walsh, and V. M. Vought. 1959. Analytical Experi-
ences with Beryllium Determinations in a Comprehensive Air Pollution
Study. Am. Ind. Hyg. Assoc. J. 20:500-503.
42. Zorn, H., and H. Diem. 1974. Die Bedeutung der Beryllium und seiner
Verbindungen fur den Arbeitsmediziner (Significance of Beryllium and
its Compounds to the Industrial Physician). Zentralbl. Arbeitsmed.
Arbeitsschutz 24:3-8.
-------
SECTION 8
ENVIRONMENTAL ASSESSMENT OF BERYLLIUM
Andrew Reeves
Wayne State University
Detroit, Michigan
8.1 ENVIRONMENTAL OCCURRENCE
8.1.1 Natural Background
Beryllium occupies the 44th place in the terrestrial abundance list
of elements. Its overall concentration in the lithosphere is estimated
at 6 yg/g. Most of it is present in localized deposits of the mineral
beryl (Be3Al2Si60a) and bertrandite [Bei,Si207(OH)2], two commercially ex-
ploitable beryllium ores. The highly treasured gemstones, emerald and
aquamarine, are colored variants of beryl. Other beryllium-containing
minerals number about 30 and include such other semiprecious stones as
euclas [Al(BeSiOfc)OH], phenakite (Be2SiOA), and chrysoberyl (Al2BeOA).
In ordinary rocks and soils, as well as in bituminous coals, the
concentration of beryllium ranges from 0.1 to 3 yg/g. The beryllium
content of mineral oils is estimated below 100 yg/liter and of natural
waters below 1 yg/liter. The atmosphere in uncontaminated locations is
estimated to contain less than 0.1 ng/m3 of beryllium.
8.1.2 Contribution by Human Activities
The baseline of background atmospheric beryllium has been exceeded
to some degree in most inhabited places because of fuel burning. Already
in the 1940s (i.e., before large-scale technical exploitation of beryl-
lium), atmospheric concentrations in U.S. cities were 0.3 to 3.0 ng/m3
of beryllium.
Industrial emissions that have added to the atmospheric beryllium
burden are discharges from beryllium mining, extracting, and machining;
foundry operations; ceramic plant operations; space vehicle and rocket
fuel manufacture; nuclear reactor and classified weapons manufacture;
and such associated activities as laundering beryllium workers' clothes.
These facilities are currently required to limit the ambient beryllium
concentration to 10 ng/m3 in the immediate vicinity of the plant.
A potential for beryllium emissions exists from certain rocket pro-
pellants; therefore, separate U.S. standards apply to rocket firing. Emis-
sions to the atmosphere from the latter source must not exceed 75 yg/min/m3
for "low-fired" (<500°C) beryllium oxides and 1.5 mg/min/m3 for "high-
fired" 0\d500°C) beryllium oxides, both measured within 10 to 60 min,
accumulated during any two consecutive weeks, at the property line or
nearest place of human habitation. Equivalent standards, if any, of other
nations are not in the public information domain. Some observers believe
192
-------
193
that global atmospheric beryllium concentrations may have increased some-
what during recent decades. The extent of increase is controversial and
at this time probably not significant.
8.2 TOXICITY
8.2.1 From Skin Contact
The handling of water-soluble beryllium salts [BeF2, BeCl2, Be(N03)2,
and BeSOi,] causes eczematous contact dermatitis which is of allergic ori-
gin and based on "delayed" (cell-mediated) hypersensitivity. Once hyper-
sensitivity is established, elicitation of skin reaction can occur after
contact with very dilute (less than 1 mg beryllium per liter) solutions.
Dermatitis is not known to occur after handling insoluble beryllium com-
pounds [BeO, Be(OH)2, BeHP04, and Be2SiOi,], the metal, or its alloys.
However, the latter substances can cause granulomatous ulceration of the
skin if they become imbedded after trauma. Systemic adsorption from the
skin is minimal for all beryllium compounds, including the soluble, and
not known to have toxic effects.
8.2.2 From Ingestion
Beryllium compounds are not well absorbed from the gastrointestinal
tract because at intestinal pH the beryllium ion tends to form insoluble
precipitates, mainly the phosphate. Massive beryllium feeding to experi-
mental animals led to rickets due to induced phosphorus deficiency, but
no other harmful consequences were observed. Such quantities of beryl-
lium that are absorbed are partly excreted through the urine and partly
deposited in the skeleton. There is no significant biomagnification.
8.2.3 From Inhalation
The high toxicity of beryllium compounds is manifested only after
inhalation. Two separate clinical entities were observed in humans: (1)
acute chemical pneumonitis, resulting promptly from inhalation of aero-
sols of soluble beryllium compounds in high concentrations (>1 mg/m3) and
(2) chronic pulmonary granulomatosis ("berylliosis"), developing slowly
(in the course of years) after inhalation of either soluble or insoluble
compounds, sometimes in very low concentrations OvLO yg/m3) .
The acute pneumonitis was seen mainly in beryllium extraction plants
and often involved all segments of the respiratory tract. The acidity
of beryllium salt solutions was the probable etiologic factor and there
appeared to be a definite dose-response relation with respect to rapid-
ity of onset, severity, and duration of the inflammation. Although there
were some fatalities resulting from the acute syndrome, recovery after
several weeks or months was the rule and no nonoccupational cases were
observed.
Chronic berylliosis has been frequently described as a "systemic"
intoxication because of eventual involvement of the adrenals, liver, kid-
ney, and heart. However, the essential original lesion is pulmonary gran-
ulomatous inflammation resembling sarcoidosis. It may develop insidiously
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up to 20 years after exposure, with or without previous history of the
acute syndrome, and can result in considerable mortality. This condition
appeared to be most often caused by insoluble beryllium compounds, espe-
cially "low-fired" BeO which has more extensive internal surfaces and
therefore much more biological activity than "high-fired" BeO. A dose-
response relation between extent of exposure and severity of disease is
emphatically absent, with workers from the cleanest plants and "neighbor-
hood cases" sometimes showing the worst clinical forms. The syndrome is
apparently a manifestation of an "auto-immune" response to beryllium as a
hapten (a substance with capability to combine with normal body constit-
uents and render them antigenic).
Beryllium sulfate inhalation has caused pulmonary tumors in rats and
monkeys, but not in guinea pigs. The epidemiological evidence in humans
is controversial; the preponderance of evidence indicates that beryllium
is probably not carcinogenic, or at most very weakly carcinogenic, in man.
8.3 SAFE LEVELS
8.3.1 Air
The occupational exposure standard for beryllium in the United States
is presently 2 yg/m3; this figure is a "time-weighed average" for an 8-hr
workday, allowing short-term excursions over the limit up to 25 yg/m3 for
up to four 15-min periods daily, provided that there is at least 1 hr
elapsed time between the excursions and that there are compensatory excur-
sions under the limit. Western European countries and Japan have also
adopted the U.S. standard. Reduction of.the U.S. standard to 1 yg/m3,
with a short-term excursion limit of 5 yg/m3, is presently pending with
the U.S. Occupational Safety and Health Administration. In the Soviet
Union, the maximum allowable concentration for beryllium is 1 yg/m3.
The margin of safety incorporated in these limits is not known with
certainty. Before adoption of the U.S. occupational exposure standard of
2 yg/m3 in 1949, acute pneumonitis and chronic berylliosis prevalence in
the beryllium industry was 1% to 3%, but in-plant concentrations at that
time were retrospectively estimated to have been in the 1 mg/m3 area.
There were also "neighborhood cases" in the population living within about
one mile from the plant; these cases were originally attributed to air
pollution of about 0.1 yg/m3 of beryllium originating from stack gases,
but it now seems probable that afflicted patients may have had direct
contact with a contaminated person or object and were in fact occasion-
ally exposed to substantially higher concentrations.
After adoption of the 2 yg/m3 standard, acute beryllium pneumonitis
cases have become very rare and confined to accidental exposures. Chronic
berylliosis incidence also declined but did not altogether disappear: 76
new cases have been reported during the last ten years, of which about
one-half received exposure since promulgation of the standard. It should
be added, however, that the new cases appear to have originated during
construction periods in beryllium plants or from newly installed opera-
tions, suggesting temporary noncompliance with the standard. The best
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judgment of informed specialists at this time is that the existing in-
plant standard of 2 yg/m3, if enforced, is adequate to prevent acute and
chronic beryllium disease in the plant population.
The recently announced intent of the U.S. Occupational Safety and
Health Administration to reduce the beryllium standard from 2 to 1 yg/m3
is based largely on the carcinogenic suspicion. Experimental animal expo-
sures have caused lung tumors in some (not all) of the species tested, but
some of the work is equivocal and the degree of malignancy of the tumors
is uncertain. The human epidemiologic evidence for beryllium cancers is
also controversial at present and is regarded by some (not all) observers
as essentially negative. Even if the carcinogenic evidence were stronger,
there are no good quality research data at present to suggest a safe thresh-
old for this assumed effect and the suggestion to tighten the standard is
made in conformity with the general policy to reduce exposure to the limit
of technical feasibility.
Short-term public limits (STPLs) and public emergency limits (PELs)
have been recommended by the.U.S. National Research Council. For beryl-
lium, the recommended figures were STPL = 5 yg/m3 for 10 min and PEL = 100
yg/m3 for 10 min. Both of these are "ceiling" values, which may be extrap-
olated on a concentration x time basis to longer, but not to shorter, expo-
sure times. The STPLs are applicable to predictable and possibly repeatable
exposures, but not more often than one per quarter year. On the basis of
present knowledge, the STPLs were expected to produce no adverse health
effects even in the most sensitive population group. The PELs are applic-
able only to unpredictable exposures of the public and no more than one
exposure in a lifetime was assumed in setting this limit.
Both the STPL and the PEL for beryllium are extrapolations of the cur-
rent air quality standard of 10 ng/m3 of beryllium for limited exposure
times on a concentration x time basis. The validity of this extrapolation
is untested and it is possible that the PEL of 100 yg/10 min/m3, or even
the special air quality standard for rocket firing of 75 yg/min/m3, would
cause untoward effects especially in sensitized individuals.
8.3.2 Water
The recommended provisional limit for beryllium in waters in the
United States is presently 1 mg/liter. Since beryllium salts do not remain
in soluble form at neutral pH, it is unlikely that directly hazardous con-
centrations could build up even in contaminated waters. Experimental rats
remained essentially unaffected by up to 1.66 mg beryllium per liter in the
drinking water over a period of six months. However, 0.5 to 1.0 mg beryl-
lium per liter inhibited the growth and biologic oxygen demand of sapro-
phytic bacteria and 3 to 5 mg/liter in the irrigating water appeared to
have adverse effects on garden vegetables. According to presently avail-
able knowledge, no biologic effects of any kind would be expected from
beryllium in concentrations up to 100 yg/liter water. A suitable standard,
with some margin for safety and not difficult to meet under normal condi-
tions, appears to be about 50 yg/liter in public waters.
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8.3.3 Foods
The highest beryllium level in food was obtained in 1974 in Germany
for green head lettuce (0.33 yg/g dry substance; the water content of
fresh vegetables averages about 90%). Potatoes, tomatoes, bread, and
rice had somewhat less beryllium (0.08 to 0.24 yg/g dry substance), but
all of these levels were almost two orders of magnitude higher than what
was reported for similar food crops from Australia (0.01 to 0.1 yg beryl-
lium per gram of ash; ash content of vegetables averages about 1% of fresh
weight). Seafood was found to have 0.1 to 1.0 yg beryllium per gram of
ash in the Australian tests.
The discrepancy between the Australian and German analytical figures
for beryllium in food crops may be either artifactual or real. An arti-
factual difference would exist if there was loss of beryllium during ash-
ing which could make the Australian figures too low, or errors due to
background contamination which could make the German figures too high.
If the difference is real, it would have to be attributed to higher fall-
out of beryllium from the air in the northern hemisphere, possibly due
to rocket firings.
In any case, there is no indication that beryllium levels in food
anywhere today are near hazardous concentration. If a standard needs to
be set, it appears feasible to use the level recommended for public waters
(about 50 ng beryllium per gram of fresh food).
8.3.4 Cigarettes
The only figures for beryllium in cigarettes originate from the same
work cited above for German vegetables, and it may be subject to the same
uncertainties. In three brands of West German cigarettes, 0.47, 0.68, and
0.74 ug beryllium per cigarette were found, with 4.5%, 1.6%, and 10.0% of
the beryllium content, respectively, escaping into the smoke during smoking.
Calculations show that for a 2.5 pack per day cigarette smoker (50
cigarettes per day) with 10 liter/min respiratory volume, and assuming 10%
of beryllium content escaping into the smoke during smoking, cigarettes
with an average of 2.0 pg beryllium per cigarette would provide an expo-
sure equivalent to the present U.S. occupational exposure limit. However,
in view of the other toxic substances in cigarette smoke with which beryl-
lium may act synergistically, and of the possibility that persons occupa-
tionally exposed to inhalation of beryllium may smoke as well, it appears
essential to reduce beryllium exposure from cigarettes to much below this
figure. A limit of 0.2 to 0.3 yg beryllium per cigarette appears desir-
able and in view of the figures cited above, it is possible that such a
limit may already have been exceeded in certain cigarettes. Since ciga-
rette smoke, unlike water or food, enters the lung directly, the promulga-
tion of a standard for cigarettes should have much higher priority than
standards for public waters or food.
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8.4 MONITORING OF SAFE LEVELS
8.4.1 Direct Analysis
Modern methods of beryllium analysis are gas chromatography and atomic
absorption spectrophotometry. The former method has the greatest sensitiv-
ity of all analytical procedures for beryllium and provides a limit of
detection of 0.0004 to 0.01 ng of beryllium per sample. Atomic absorption
spectrophotometry is appealing for its simplicity and has a. limit of detec-
tion of about 40 ng of beryllium per sample.
The classical methods of beryllium analysis by colorimetric, fluoro-
metric, or spectrographic techniques are losing popularity because of the
requirement of cumbersome preparatory procedures. interference by other
metals, or inferior precision. Their limit of detection is in the range
of 0.01 to 100 ng per sample of beryllium.
Since the levels of beryllium which may be encountered in biological
materials or air are likely to be low, extreme precautions to avoid con-
tamination or loss must be observed. Borosilicate glassware should be used
exclusively, freshly cleansed for each determination with chromate-sulfuric
acid, followed by rinsing with deionized water. Beryllium solutions, includ-
ing urine specimens collected for analysis, must be acidified even for short
periods of storage in order to avoid adsorption of beryllium on the vessel
wall. Even well-qualified chemists, if they have no specific experience in
microanalysis, are likely to experience difficulties, and the widely dis-
crepant data on the beryllium content of foods and other consumer products
in the literature must be viewed with caution.
8.4.2 Biological Monitoring
In human pulmonary tissue, amounts less than 20 ng/g of beryllium (dry
weight basis) are not regarded as indicative of occupational exposure; in
exposed workers, the levels may be as high as several micrograms per gram.
However, there is no quantitative correlation between pulmonary beryllium
and severity of berylliosis. Often, various segments of the same lung
exhibited widely differing levels.
Urinary excretion of measurable quantities of beryllium (0.02 to 3.0
yg/liter) is indicative of occupational exposure but is not consistently
observed and may occur in healthy workers as well as in workers suffering
from beryllium poisoning. Thus, urine levels are not suitable as depend-
able monitors of a hazardous exposure or as diagnostic acids in berylliosis.
8.5 SUMMARY OPINION AND RESEARCH NEEDS
Beryllium compounds are present in the normal atmosphere at levels of
0.1 to 3.0 ng/m3; in natural waters at levels of 0.1 to 1.0 yg/liter; and
in ordinary soils at levels of 0.1 to 3.0 yg/g. Foods were reported to con-
tain up to 33 ng/g of beryllium in fresh substance, and tobacco smoke up to
74 ng beryllium per cigarette.
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Ingested beryllium compounds at these levels, or even at several
times these levels, are harmless. A suitable standard for beryllium in
fresh foods and public waters, based on present knowledge, is about 50
ng/g.
Inhaled beryllium compounds have acute as well as considerable chronic
toxicity, and perhaps carcinogenicity, in the several micrograms of beryl-
lium per cubic meter concentration range. The toxicity of beryllium oxides
is inversely related to their firing temperatures during production, due
to the varying area of internal surfaces in the powders. Only "low-fired"
(<500°C) beryllium oxide appears to pose a high degree of toxic hazard.
The thresholds of harmful concentrations are not known with certainty. An
occupational exposure standard of 2 yg/m3 of beryllium, promulgated in 1949,
has prevented acute and perhaps chronic berylliosis; the carcinogenesis evi-
dence is controversial. United States air quality standards are presently
set at 10 ng/m3 of beryllium with the exception of rocket firings, where 75
ug/min/m3 for low-fired beryllium oxide and 1.5 mg/min/m3 for high-fired
beryllium oxide are permitted. Reduction of the occupational exposure
limit from 2 to 1 ug/m3 is presently pending with the U.S. Occupational
Safety and Health Administration.
The limits presently in force or pending appear to be adequate, with
the possible exception of the special limits for rocket firings which could
produce untoward effects in sensitized individuals. The most serious prob-
lem of rocket firings, even at high altitudes, appears to be beryllium fall-
out on crops, specifically tobacco. The presently measured beryllium content
of tobacco could cause beryllium inhalation exceeding the threshold limit
equivalent in a heavy smoker. It is recommended to establish a standard
for smoking tobacco at about 25 ng/g.
Outstanding research needs are to resolve the suspected carcinogeni-
city of beryllium in various species with better definition of the degree
of malignancy of the obtained tumors; to investigate the relative biologi-
cal responses to low- and high-fired beryllium oxides in the immunological
area; to obtain dose-response information for short-term exposures and for
long-term low-level exposures; and to survey worldwide incidence of condi-
tions diagnosed as sarcoidosis and correlate it to local beryllium content
of air, water, and crops.
US.GOVERNMENT PRINTING OFFICE: 1979-748-189/361
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TECHNICAL REPORT DATA
(Please read Instructions on the reverse before completing)
1. REPORT NO.
2.
3. RECIPIENT'S ACCESSION-NO.
4. TITLE AND SUBTITLE
Reviews of the Environmental Effects of Pollutants:
VI. Beryllium
5. REPORT DATE
6. PERFORMING ORGANIZATION CODE
7. AUTHOR(S)
8. PERFORMING ORGANIZATION REPORT NO.
9. PERFORMING ORGANIZATION NAME AND ADDRESS
Information Center Complex, Information Division
Oak Ridge National Laboratory
Oak Ridge, Tennessee 37830
10. PROGRAM ELEMENT NO.
1HA616
11. CONTRACT/GRANT NO.
IAG D5-0403
12. SPONSORING AGENCY NAME AND ADDRESS
Health Effects Research Laboratory Cin-OH
Office of Research and Development
U.S. Environmental Protection Agency
Cincinnati. Ohio 45219
13. TYPE OF REPORT AND PERIOD COVERED
Final
14. SPONSORING AGENCY CODE
EPA/600/10
15. SUPPLEMENTARY NOTES
16. ABSTRACT
This is a review of the scientific literature on the biological and environ-
mental effects of beryllium. Included in the review are a general summary and a
comprehensive discussion of the following topics as related to beryllium and
specific beryllium compounds: physical and chemical properties; occurrence;
synthesis and use; analytical methodology; biological aspects in microorganisms,
plants, wild and domestic animals, and humans; distribution, mobility, and
persistence in the environment; assessment of present and potential health and
environmental hazards; and review of standards and governmental regulations.
More than 300 references are cited.
17.
KEY WORDS AND DOCUMENT ANALYSIS
DESCRIPTORS
b.lDENTIFIERS/OPEN ENDED TERMS
c. COSATI Field/Group
*Pollutants
Toxicology
Beryllium
Health Effects
06F
06T
18. DISTRIBUTION STATEMENT
Release to Public
19. SECURITY CLASS (ThisReport)
Unclassified
21. NO. OF PAGES
20. SECURITY CLASS (Thispage)
Unclassified
22. PRICE
EPA Form 2220-1 (9-73)
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