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    policy of the United Nations Environment Programme, the International
    Labour Organisation, or the World Health Organization.

    Published under the joint sponsorship of
    the United Nations Environment Programme,
    the International Labour Organisation,
    and the World Health Organization

    World Health Orgnization
    Geneva, 1990

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        (Environmental health criteria ; 106)


        ISBN 92 4 157106 3        (NLM Classification: QV 275)
        ISSN 0250-863X

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     1.1. Identity, physical and chemical properties, analytical 
     1.2. Sources of human and environmental exposure  
     1.3. Environmental transport, distribution, and 
     1.4. Environmental levels and human exposure  
     1.5. Kinetics and metabolism  
     1.6. Effects on organisms in the environment   
     1.7. Effects on experimental animals and  in vitro test 
     1.8. Effects on human beings  
     1.9. Evaluation of human health risks and effects on the 
           1.9.1. Human health risks  
           1.9.2. Effects on the environment  


     2.1. Identity     
           2.1.1. Pure beryllium and beryllium compounds  
           2.1.2. Impure beryllium compounds  
     2.2. Physical and chemical properties  
     2.3. Analytical methods  
           2.3.1. Sampling procedure and sample preparation  
            Sample decomposition  
            Separation and concentration   
           2.3.2. Detection and measurement  


     3.1. Natural occurrence  
     3.2. Man-made sources  
           3.2.1. Industrial production and processing   
            Production levels   
            Manufacturing process  
            Emissions during production and use
            Disposal of wastes  
           3.2.2. Coal and oil combustion  
     3.3. Uses      


     5.1. Environmental levels   
           5.1.1. Ambient air  
           5.1.2. Surface waters and sediments  
           5.1.3. Soil     

           5.1.4. Food and drinking-water  
           5.1.5. Tobacco    
           5.1.6. Environmental organisms  
     5.2. General population exposure  
     5.3. Occupational exposure  
           5.3.1. Exposure levels  
           5.3.2. Occupational exposure standards  
           5.3.3. Biological monitoring  
     6.1. Absorption     
           6.1.1. Respiratory absorption   
           6.1.2. Dermal absorption  
           6.1.3. Gastrointestinal absorption  
     6.2. Distribution and retention   
     6.3. Elimination and excretion  
     6.4. Biological half-life  
     7.1. Microorganisms  
     7.2. Aquatic organisms  
           7.2.1. Plants    
           7.2.2. Animals    
     7.3. Terrestrial organisms  
           7.3.1. Plants    
           7.3.2. Animals    

     8.1. Single exposures  
     8.2. Short- and long-term exposures  
           8.2.1. Short-term exposure  
           8.2.2. Long-term exposure   
     8.3. Skin irritation and sensitization  
     8.4. Reproduction, embryotoxicity, and teratogenicity  
     8.5. Mutagenicity and related end-points  
           8.5.1. DNA damage  
           8.5.2. Mutation  
            Bacteria and yeast  
            Cultured mammalian cells  
           8.5.3. Chromosomal effects   
     8.6. Carcinogenicity    
           8.6.1. Bone cancer   
           8.6.2. Lung cancer  
     8.7. Mechanisms of toxicity, mode of action  
           8.7.1. Effects on enzymes and proteins  
           8.7.2. Immunological reactions  
     9.1. General population exposure  
     9.2. Occupational exposure  
           9.2.1. Effects of short- and long-term exposure  
            Acute disease   
            Chronic disease  
     9.3. Carcinogenicity   
           9.3.1. Epidemiological studies  
     10.1. Evaluation of human health risks  
     10.2. Evaluation of effects on the environment  
     10.3. Conclusions     
           10.3.1. Acute beryllium disease  
           10.3.2. Chronic beryllium disease  
           10.3.3. Cancer    



Dr V. Bencko, Institute of Tropical Health, Postgraduate School of 
   Medicine and Pharmacy, Prague, Czechoslovakia 

Dr A.W. Choudhry, Division of Environmental and Occupational 
   Health, Kenya Medical Research Centre (KEMRI), Nairobi, Kenya 

Dr R. Hertel, Fraunhofer Institute of Toxicology and Aerosol 
   Research, Hanover, Federal Republic of Germany 

Dr P.F. Infante, Office of Standards Review, Occupational Safety 
   and Health Administration, US Department of Labor, Washington, 
   DC, USA 

Professor A. Massoud, Department of Community, Environmental and 
   Occupational Medicine, Ain Shams University, Abbassia, Cairo, 

Dr L.A. Naumova, Institute of Industrial Hygiene and Occupational 
   Diseases, Moscow, USSR  (Vice-Chairman) 

Professor A.L. Reeves, Faculty of Allied Health Professions, 
   Department of Occupational and Environmental Health, Wayne State 
   University, Detroit, Michigan, USA 

Dr G. Rosner, Fraunhofer Institute of Toxicology and Aerosol 
   Research, Hanover, Federal Republic of Germany  (Rapporteur) 

 Representatives of Nongovernmental Organizations 

Dr A.V. Roscin, representative of the International Commission on 
   Occupational Health (ICOH), also a designated national observer, 
   Central Institute for Advanced Medical Training, Moscow, USSR 


Dr N.A. Khelkovsky-Sergeev, Institute of Industrial Hygiene and 
   Occupational Diseases, Moscow, USSR 


Dr Z. Grigorevskaya, Centre for International Projects, Moscow, 
   USSR  (Project Officer) 

Dr E.M. Smith, International Programme on Chemical Safety, Division 
   of Environmental Health, World Health Organization, Geneva, 
   Switzerland  (Secretary) 

Dr V. Turosov (also representing International Agency for Research  
   on Cancer), Cancer Research Center, Academy of Medical Sciences 
   of the USSR, Moscow, USSR 


    Every effort has been made to present information in the 
criteria documents as accurately as possible without unduly 
delaying their publication.  In the interest of all users of the 
environmental health criteria documents, readers are kindly 
requested to communicate any errors that may have occurred to the 
Manager of the International Programme on Chemical Safety, World 
Health Organization, Geneva, Switzerland, in order that they may be 
included in corrigenda, which will appear in subsequent volumes. 

                            *    *    *

    A detailed data profile and a legal file can be obtained from 
the International Register of Potentially Toxic Chemicals, Palais 
des Nations, 1211 Geneva 10, Switzerland (Telephone no. 


    A WHO Task Group on Environmental Health Criteria for Beryllium 
met at the Ukrania Hotel, Moscow, USSR, from 3 to 7 July 1989,  
under the auspices of the USSR State Committee for Environmental 
Protection, Centre for International Projects.  Dr S.N. Morozov 
welcomed the participants on behalf of the host institution and 
Dr E. Smith opened the meeting on behalf of the three cooperating 
organizations of the IPCS (ILO/UNEP/WHO).  The Task Group reviewed 
and revised the draft criteria document and made an evaluation of 
the health risks of exposure to beryllium.  

    The first draft of this document was prepared by Dr R. HERTEL 
and Dr G. ROSNER, Fraunhofer Institute for Toxicology and Aerosol 
Research, Hanover, Federal Republic of Germany.  This draft was 
reviewed in the light of international comments by a Working Group 
comprising Dr V. BENCKO, Prague, Czechoslovakia, Dr M. PISCATOR, 
Stockholm, Sweden, Dr F.W. SUNDERMAN, Farmington, Connecticut, USA, 
with the assistance of Dr R. Hertel and Dr G. Rosner.  The revised 
draft resulting from this Working Group was submitted for the Task 
Group review.  Dr E. SMITH, IPCS Central Unit, was responsible for 
the overall scientific content of the document and the organization 
of the meetings, and Mrs M.O. HEAD of Oxford, England, was 
responsible for the editing. 

    The efforts of all who helped in the preparation and 
finalization of the document are gratefully acknowledged. 

                             *   *   * 

    Financial support for the Task Group was provided by the United 
Nations Environment Programme, through the USSR Commission for 
UNEP.  Partial financial support for the publication of this 
criteria document was kindly provided by the United States 
Department of Health and Human Services, through a contract from 
the National Institute of Environmental Health Sciences, Research  
Triangle Park, North Carolina, USA-a WHO Collaborating Centre for 
Environmental Health Effects. 

1.1  Identity, Physical and Chemical Properties, Analytical Methods

    Beryllium is a steel-grey, brittle metal, existing naturally 
only as the 9Be isotope.  Its compounds are divalent.  Beryllium 
has several unique  properties.  It is the lightest of all solid  
and chemically-stable substances, with an unusually high melting 
point, specific heat, heat of fusion, and strength-to-weight ratio.  
It has excellent electrical and thermal conductivities.  Because of 
its low atomic number, beryllium is very permeable to X-rays.  Its 
nuclear properties include the breaking, scattering, and reflecting 
of neutrons, as well as the emission of neutrons on alpha-

    Beryllium has a number of chemical properties in common with 
aluminium, particularly its high affinity for oxygen.  Hence, a 
very stable surface film of beryllium oxide (BeO) is formed on the 
surface of metallic beryllium and beryllium alloys, providing high 
resistance to corrosion, water, and cold oxidizing acids.  When 
ignited in oxygen, beryllium powder burns with a temperature of 
4500 °C.  Sintered beryllium oxide ("beryllia") is very stable and 
possesses ceramic properties.  Cationic beryllium salts are 
hydrolysed in water and react to form insoluble hydroxides or 
hydrated complexes at pH values in the range of 5 - 8, and 
beryllates, above pH 8. 

    As an additive in alloys, beryllium confers a combination of 
outstanding properties on other metals, particularly, resistance to 
corrosion, high modulus of elasticity, non-magnetic and non-
sparking characteristics, increased electrical and thermal 
conductivities, and a greater strength than that of steel. 

    A variety of analytical methods have been used to determine 
beryllium in various media.  Older methods include spectroscopic, 
fluorometric, and spectrophotometric techniques.  Flameless atomic 
absorption spectrometry and gas chromatography are the methods of 
choice; the detection limits are 0.5 ng/sample (flameless atomic 
absorption) and 0.04 pg/sample (gas chromatography with electron-
capture detection).  In addition, inductively coupled plasma atomic 
emission spectrometry is being increasingly used. 

1.2  Sources of Human and Environmental Exposure

    Beryllium is the 35th most abundant element in the earth's 
crust, with an average content of about 6 mg/kg.  Apart from the 
gemstones, emerald (chromium-containing beryl) and aquamarine 
(iron-containing beryl), only 2 beryllium minerals are of economic 
significance.  Beryl contains up to 4% of beryllium and is mined in 
Argentina, Brazil, China, India, Portugal, the USSR, and in several 
countries in southern and central Africa.  Although it contains 
less than 1% beryllium, bertrandite has become the main source of 
this metal in the USA. 

    The annual global production of beryllium minerals in the 
period 1980 - 84 was estimated to be around 10 000 tonnes, which 
corresponds to approximately 400 tonnes of beryllium.  Despite the 
considerable fluctuations in beryllium supply and demand resulting 
from sporadic government programmes in armaments, nuclear energy, 
and aerospace, demand for beryllium was expected, in 1986, to 
increase at an average annual rate of about 4% up to 1990. 

    In general, beryllium emissions during production and use are 
of minor importance compared with emissions that occur during the 
combustion of coal and fuel oil, which have natural average 
contents of 1.8 - 2.2 mg Be/kg dry weight, and up to 100 µg 
Be/litre, respectively.  Beryllium emission from the combustion of 
fossil fuels amounted to approximately 93% of the total beryllium 
emission in the USA, one of the main producer countries.  Improved 
control measures can substantially reduce the emission of beryllium 
from power plants. 

    Though the combustion of fossil fuels determines the beryllium 
background levels in ambient air, production-related sources can 
lead to locally elevated ambient concentrations, particularly where 
there are insufficient control measures.  Similarly, emissions 
arising from the testing and use of beryllium-powered rockets could 
be of potential local significance.  In occupational settings, 
exposure occurs mainly during the processing of beryllium ores, 
metallic beryllium, beryllium-containing alloys, and beryllium 
oxide.  Production industries exist only in Japan, the USA, and the 
USSR.  In other countries, the imported pure metal, alloys, or 
ceramic beryllium oxide are processed to end products. 

    Most beryllium waste results from pollution control measures 
and is either recycled or buried.  Recycling of the majority of 
end-products is not economically worth while because of their small 
volume and low beryllium content. 

    Approximately 72% of the world production of beryllium is used 
in the form of beryllium-copper and other alloys in the aerospace, 
electronics, and mechanical industries.  About 20% is used as the 
free metal, mainly in the aerospace, weapons, and nuclear 
industries.  The remainder is used as beryllium oxide for ceramic 
applications, principally in electronics and microelectronics. 

1.3  Environmental Transport, Distribution, and Transformation

    Data concerning the fate of beryllium in the environment are 
limited.  Atmospheric beryllium oxide particles return to earth 
through wet and dry deposition.  Within the environmental pH range 
of 4 - 8, beryllium is strongly absorbed by finely-dispersed 
sedimentary minerals, thus preventing release to ground water. 

    Beryllium is believed not to biomagnify to any extent within 
food chains.  Most plants take up beryllium from the soil in small 
amounts, and very little is translocated from the roots to other 
plant parts. 

1.4  Environmental Levels and Human Exposure

    Beryllium concentrations in surface and drinking-waters are 
usually in the low µg/litre range.  Levels in soils range between 1 
and 7 mg/kg.  Terrestrial plants generally contain less than 1 mg 
beryllium/kg dry weight.  Amounts of up to approximately 100 µg/kg 
fresh weight have been found in various marine organisms. 

    Atmospheric beryllium concentrations at rural sites in the USA 
ranged from 0.03 to 0.06 ng/m3.  In countries with less fossil fuel 
combustion, background levels should be lower.  Annual average 
beryllium concentrations in urban air in the USA were found to 
range from <0.1 to 6.7 ng/m3.  In Japanese cities, an average of 
0.04 ng/m3 was found with the highest values (0.2 ng/m3) occurring 
in industrial areas. 

    Before the establishment of control measures in the 1950s, 
atmospheric beryllium concentrations were extremely high in the 
vicinity of production and processing plants.  In addition, 
"para-occupational" exposure used to occur in workers' families, 
known as neighbourhood cases, which were related to contact with 
the worker's clothes, atmospheric exposure, or both.  Today, these 
sources of exposure are normally insignificant for the general 
population.  The principal source of environmental exposure of the 
general population to airborne beryllium is the combustion of 
fossil fuels.  Exceptionally high exposure could occur in the 
vicinity of power plants that burn coal containing high levels of 
beryllium and do not apply adequate control measures.  Tobacco 
smoking is probably another important source of beryllium exposure. 

    The growing use of beryllium in base dental casting alloys 
could be of some significance for the general population, because 
of the high potential of beryllium to provoke contact allergic 

    Prior to 1950, exposure to beryllium in working environments 
was usually very high, and concentrations exceeding 1 mg/m3 were 
not unusual.  Control measures to meet the occupational standards 
of 1 - 5 µg Be/m3 (time-weighted average), established by various 
countries, have drastically reduced work-place concentrations of 
beryllium, though these values are not being achieved everywhere. 

    Levels of beryllium in tissues or body fluids may be indicative 
of a previous exposure situation.  In persons who have not been 
specifically exposed, levels in the urine are around 1 µg/litre and 
those in lung tissue, less than 20 µg/kg (dry weight).  The limited 
data available do not allow the substantiation of a clear 
relationship between exposure and body burden, though clearly 
elevated levels (>20 µg/kg) have been found in lung tissue samples 
from patients with beryllium disease. 

1.5  Kinetics and Metabolism

    There are no human data on the deposition or absorption of 
inhaled beryllium.  Animal studies have shown that, after being 
deposited in the lungs, beryllium remains there and is slowly 
absorbed into the blood.  Pulmonary clearance is biphasic, with a 
fast elimination phase in the first 1 - 2 weeks following cessation 
of exposure. 

    Most of the beryllium circulating in the blood is transported 
in the form of a colloidal phosphate.  A significant part of the 
inhaled dose is incorporated into the skeleton, which is the 
ultimate site of beryllium storage.  Generally, inhalation exposure 
also results in long-term storage of appreciable amounts of 
beryllium in lung tissue, particularly in pulmonary lymph nodes.  
More soluble beryllium compounds are also translocated to the 
liver, abdominal lymph nodes, spleen, heart, muscle, skin, and 

    Following oral administration of beryllium, a small amount 
(less than 1% of the dose) is generally absorbed into the blood and 
stored in the skeleton.  Small amounts have also been found in the 
gastrointestinal tract and in the liver. 

    The absorption of beryllium through intact skin is negligible, 
as beryllium is bound by epidermal constituents. 

    A considerable proportion of absorbed beryllium is rapidly 
eliminated, mainly in the urine, and, to a small extent, in the 
faeces.  Part of inhaled beryllium is also eliminated in the 
faeces, probably as a result of clearance from the respiratory 
tract and ingestion of swallowed beryllium. 

    Because of the long storage of beryllium in the skeleton and 
lungs, its biological half-life is extremely long.  A half-life of 
450 days has been calculated for the human skeleton. 

1.6  Effects on Organisms in the Environment

    Soil microorganisms grown in a magnesium-deficient medium grow 
better in the presence of beryllium, because of the partial 
substitution of beryllium for magnesium in the organisms' 
metabolism.  Similar growth-stimulating effects have been noted in 
algae and crop plants.  This phenomenon seems to be pH-dependent, 
as it only occurs at high pH.  At pH 7 or below, beryllium is toxic 
for aquatic and terrestrial plants, regardless of the magnesium 
levels in the growth medium. 

    Generally, plant growth is inhibited by soluble beryllium 
compounds at mg/litre concentrations.  For example, in bush beans 
 (Phaseolus vulgaris) grown in nutrient solution at pH 5.3, an 88% 
yield reduction was observed at a concentration of 5 mg Be/litre.  
Effects were first observed on the roots, which turned brown and 
failed to resume normal elongation.  Roots accumulate most of the 
beryllium taken up, and very little is translocated to the upper 

parts of the plant.  The critical contents of beryllium resulting 
in a 50% decrease in yield were estimated to be about 3000 mg Be/kg 
dry weight and 6 mg Be/kg, respectively, in the roots and outer 
leaves of cabbage plants  (Brassica oleracea). 

    Stunting of both roots and foliage was noted in soil cultures 
of beans, wheat, and ladino clover, but no chlorosis or mottling of 
the foliage occurred. 

    In soil culture, beryllium phytotoxicity is governed by the 
nature of soil, particularly its cation exchange capacity and the 
pH of the soil solution.  Apart from the magnesium-substituting 
effect, the diminished phytotoxicity under alkaline conditions also 
results from the precipitation of beryllium as unavailable 
phosphate salt. 

    The mechanism underlying the phytotoxicity of beryllium is 
probably based on the inhibition of specific enzymes, particularly 
plant phosphatases.  Beryllium also inhibits uptake of essential 
mineral ions. 

    In acute toxicity studies on different freshwater fish species, 
LC50 values were found to vary from 0.15 to 32 mg Be/litre, 
depending on species and test conditions.  Toxicity to fish 
increased with decreasing water hardness; beryllium sulfate was one 
to two orders of magnitude more toxic for fathead minnows and 
bluegills in soft water than in hard water.  Salamander larvae and 
the waterflea  (Daphnia magna) showed a similar sensitivity. 

    There are no validated data on the long-term toxicity of 
beryllium in aquatic animals.  However, one unpublished study has 
provided evidence of  Daphnia magna being adversely affected at 
considerably lower concentrations (5 µg Be/litre) in long-term 
reproduction tests than in acute toxicity tests (EC50, 2500 µg 

1.7  Effects on Experimental Animals and  In Vitro Test Systems

    Symptoms of acute beryllium poisoning in experimental animals 
were respiratory disorders, spasms, hypoglycaemic shock, and 
respiratory paralysis. 

    Implantation of beryllium compounds and metallic beryllium in 
the subcutaneous tissues may produce granulomas, similar to those 
observed in human beings.  Guinea-pigs developed cutaneous 
hypersensitivity on intradermal injection of soluble beryllium 

    As a secondary effect, beryllium carbonate produced rickets 
(rachitis) in young rats, through intestinal precipitation of 
beryllium phosphate and concomitant phosphorus deprivation. 

    Acute chemical pneumonitis occurred in various animal species 
following the inhalation of beryllium metal or different beryllium 
compounds, including insoluble forms.  Repeated daily exposure to 

beryllium sulfate mist, at a mean concentration of 2 mg Be/m3, was 
lethal for rats (90% deaths), dogs (80%), cats (80%), rabbits 
(10%), guinea-pigs (60%), monkeys (100%), goats (100%), hamsters 
(50%), and mice (10%).  Because of a synergistic effect of the 
fluoride ion, the effects of beryllium fluoride were about twice as 
great as those of the sulfate.  Some of the lesions in the lungs 
resembled those in man, but the granulomas were not identical. 

    The inhalation toxicity of insoluble beryllium oxide depends to 
a great extent on its physical and chemical properties, which can 
alter considerably, depending on production conditions.  Because 
its ultimate particle size is smaller and there is less 
aggregation, low-fired BeO (400 °C) at 3.6 mg Be/m3 for 40 days 
caused mortality in rats and marked lung damage in dogs, whereas 
high-fired BeO grades (1350 °C and 1150 °C) did not produce 
pulmonary damage, in spite of a higher total exposure (32 mg Be/m3, 
360 h). 

    The characteristic non-malignant response to long-term, low-
level inhalation exposure to soluble and insoluble beryllium 
compounds is chronic pneumonitis associated with granulomas, which 
only partly corresponds to the chronic disease seen in humans 

    The results of genotoxicity tests indicate that beryllium 
interacts with DNA and causes gene mutations, chromosomal 
aberrations, and sister chromatid exchange in cultured mammalian 
somatic cells, though it was not mutagenic in bacterial test 

    Intravenous (3.7 - 700 mg Be) and intramedullary (0.144 - 216 
mg Be) injection of beryllium metal and various compounds produced 
osteosarcomas and chondrosarcomas in rabbits, with metastases 
occurring in 40 - 100% of the animals, most frequently in the 

    In rats, inhalation (0.8 - 9000 µg Be/m3) or intratracheal 
(0.3 - 9 mg Be) exposure to soluble and insoluble beryllium 
compounds, beryllium metal, and various beryllium alloys induced 
lung tumours of the adenoma or adenocarcinoma type, partly 
metastasizing.  Beryl (620 µg Be/m3) was the only beryllium ore 
that caused lung carcinomas (bertrandite, at 210 µg Be/m3, did 
not).  Beryllium oxide proved carcinogenic to rats, but the 
incidence of pulmonary adenocarcinomas was much higher after 
intratracheal administration (9 mg Be) of a low-fired specification 
(51%) compared with high-fired oxides (11 - 16%).  At the time of 
many of these studies, study design and laboratory practice did not 
usually comply with current practices.  Thus, the reported 
inhalation exposure data should be considered with particular care. 

    The induction of pulmonary cancer by beryllium is highly 
species-specific.  While rats and, perhaps, monkeys are very 
susceptible in this respect, no pulmonary tumours have been 
observed in rabbits, hamsters, or guinea-pigs. 

    Mechanisms for beryllium toxicity have been based on 3 
theories:  (1) beryllium affects phosphate metabolism by inhibiting 
crucial enzymes, particularly alkaline phosphatase; (2) beryllium 
inhibits replication and cell proliferation by affecting enzymes of 
nucleic acid metabolism; and (3) beryllium toxicity involves an 
immunological mechanism, as shown in guinea-pigs, which develop 
cell-mediated hypersensivity in the skin. 

1.8  Effects on Human Beings

    Toxicologically relevant exposure to beryllium is almost 
exclusively confined to the work-place.  Before the introduction of 
improved emission control and hygiene measures in beryllium plants, 
several "neighbourhood" cases of chronic beryllium disease were 
reported.  By 1966, a total of 60 cases had been reported in the 
USA, some of which were related to contact with workers' clothes 
("para-occupational" exposure) or to air exposure in the close 
vicinity of beryllium plants.  No cases have been reported in 
recent years. 

    Recently, several cases of an allergic contact stomatitis, 
probably caused by beryllium-containing dental prostheses, have 
been reported. 

    In the 1930s and 1940s, several hundred cases of acute 
beryllium disease occurred, particularly in workers in beryllium-
extraction plants in Germany, Italy, the USA, and the USSR.  
Inhalation of soluble beryllium salts, particularly the fluoride 
and sulfate, at concentrations exceeding 100 µg Be/m3, consistently 
produced acute symptoms among almost all exposed workers, while, at 
a level of 15 µg/m3 and below (determined using out-of-date 
analytical methods), no cases were registered.  After adoption of a 
maximum exposure concentration of 25 µg/m3 in the early 1950s, 
cases of acute beryllium disease drastically decreased. 

    Signs and symptoms of acute beryllium disease range from mild 
inflammation of the nasal mucous membranes and pharynx to 
tracheobronchitis and severe chemical pneumonitis.  In severe 
cases, patients died of acute pneumonitis, but in most cases, after 
cessation of exposure, complete recovery occurred within 1 - 4 
weeks.  In a few cases, chronic beryllium disease developed years 
after recovery from the acute form. 

    Direct contact with soluble beryllium compounds causes contact 
dermatitis and possibly conjunctivitis.  Sensitized individuals 
react much more rapidly and to lower amounts of beryllium.  Soluble 
or insoluble beryllium compounds, introduced in, or beneath, the 
skin produce chronic ulcerations, with granulomas often appearing 
after several years. 

    Chronic beryllium disease differs from the acute form in having 
a latent period ranging from several weeks up to more than 20 
years; it is of long duration and progressive in severity.  In the 
US Beryllium Case Registry (a central file on reported cases of 
beryllium disease, established in 1952) 888 cases were registered 

up to 1983.  Six hundred and twenty two cases were classified as 
chronic, of which 557 resulted from occupational exposure, mainly 
within the fluorescent lamp industry (319 cases) or within 
beryllium extraction plants (101 cases).  After the use of zinc 
beryllium silicate and beryllium oxide in fluorescent tube 
phosphors was abandoned in 1949, and an occupational exposure limit 
(TWA, 2 µg Be/m3) was adopted, cases of chronic beryllium disease 
dramatically decreased, but new cases resulting from exposure to an 
air concentration of around 2 µg/m3 have been recorded. 

    The term "chronic beryllium disease" is preferred to the term 
"berylliosis", because this disease differs from a typical 
pneumoconiosis.  Granulomatous inflammation of the lung, associated 
with dyspnoea on exertion, cough, chest pain, weight loss, fatigue, 
and general weakness, is the most typical feature; right heart 
enlargement with accompanying cardiac failure, hepatomegaly, 
splenomegaly, cyanosis, and finger clubbing may also occur.  
Changes in serum proteins and liver function, renal stones, and 
osteosclerosis have also been found to be associated with chronic 
beryllium disease.  The evolution of chronic beryllium disease is 
not uniform; in some cases, spontaneous remission for weeks or 
years is encountered, followed by exacerbations.  In the majority 
of cases, progressive pulmonary disease is seen with an increased 
risk of death from cardiac or respiratory failure.  The reported 
morbidity rates among beryllium workers vary from 0.3 to 7.5%.  In 
patients with chronic beryllium disease, the mortality rates are as 
high as 37%. 

    Macroscopically, the lungs may show diffuse changes, with 
widespread scattered small nodules and interstitial fibrosis.  
Microscopically, there are sarcoid-like granulomas with varying 
amounts of interstitial inflammation, which are usually 
indistinguishable from those in other granulomatoses, such as 
sarcoidosis or tuberculosis. 

    History taking and tissue analysis serve as a valuable basis in 
the diagnosis of beryllium disease, though the presence of 
beryllium in biological material does not prove the presence of 
disease.  Patch testing is not recommended, because it is not very 
reliable and is itself highly sensitizing.  The most useful 
diagnostic aids are the macrophage migration inhibition assay and 
the lymphocyte-blast transformation test. 

    These methods of measuring hypersensitivity are based on an 
immune mechanism that probably underlies chronic beryllium disease 
and the delayed cutaneous and granulomatous hypersensitivity. 

    The great variability in latency and the lack of dose-response 
relationships in chronic beryllium disease may be explained by 
immunological sensitization.  Pregnancy seems to be a precipitating 
"stress factor", as 66% of 95 females, registered among the fatal 
cases in the US Beryllium Case Registry, were pregnant. 

    Sources of exposure for patients with beryllium disease also 
include beryllium metal alloy production, machining, ceramics 
production and research, and energy production.  The present 
occupational exposure standards may not exclude the development of 
chronic beryllium disease in sensitized individuals. 

    In several epidemiological studies, the carcinogenicity of 
beryllium has been examined among workers employed in two US 
beryllium production facilities and among clinical cases in a 
registry of beryllium-related lung conditions, derived from these 
facilities and other occupations.  The results of these studies 
have been questioned on the grounds of selection bias, confounding 
from cigarette smoking, and underestimation of the expected number 
of lung cancer deaths, since mortality rates for the period 
1965 - 67 had been used to estimate expected mortality for the 
years 1968 - 75.  While the first two issues are unlikely to have 
played a major role in the excess lung cancer risk, the data 
presented in this document have been based on an "adjusted" 
expected number of lung cancer deaths.  Significantly elevated 
risks of lung cancer were noted in all studies. 

1.9   Evaluation of Human Health Risks and Effects on 
the Environment

1.9.1  Human health risks

    Provided that the control measures in the beryllium industry 
are adequate, general population exposure today is mainly confined 
to low levels of airborne beryllium from the combustion of fossil 
fuels.  In exceptional cases, where coal with an unusually high 
beryllium content is burned, health problems could arise.  The use 
of beryllium for dental prostheses should be reconsidered, because 
of the high sensitization potential of beryllium. 

    Cases of acute beryllium disease resulting in nasopharyngitis, 
bronchitis, and severe chemical pneumonitis have drastically 
decreased and, today, may only occur as a consequence of failures 
in control measure systems.  Chronic beryllium disease differs from 
the acute form in having a latent period of several weeks to more 
than 20 years; it is of long duration and progressive in severity.  
The lung is mainly affected; granulomatous inflammation, associated 
with dyspnoea on exertion, cough, chest pain, weight loss, and 
general weakness, is the typical feature.  Effects on other organs 
may be of a secondary nature, rather than systemic.  The great 
variability in latency and the lack of dose-response may still 
occur today among sensitized individuals who have experienced 
exposure to a concentration of around 2 µg/m3. 

    Despite some deficiencies in study design and laboratory 
practice, the carcinogenic activity of beryllium in different 
animal species has been confirmed. 

    Several epidemiological studies have provided evidence of an 
excess lung cancer risk from occupational exposure to beryllium.  
Although a number of criticisms have been raised about the 

interpretation of these results, available data lead to the 
conclusion that beryllium is the most likely single explanation for 
the excess lung cancer observed in the exposed workers. 

1.9.2  Effects on the environment

    Data concerning the fate of beryllium in the environment, 
including its effects on aquatic and terrestrial organisms, are 
limited.  Beryllium levels in surface waters (µg/litre range) and 
soils (mg/kg dry weight range) are usually low and probably do not 
negatively affect the environment. 


    The element beryllium (Be) was discovered in 1798 by the French 
chemist Vauquelin, who prepared the hydroxide of beryllium.  The 
metallic element was first isolated in independent experiments by 
Wöhler (1828) and Bussy (Anon, 1828).  Owing to the sweet taste of 
its salts, the new element was called glucinium (G) by Bussy.  
Today this name is still used in the French chemical literature.  
In 1957, Wöhler's name "beryllium" was officially recognized by 
IUPAC (Ballance et al., 1978). 

2.1  Identity

2.1.1  Pure beryllium and beryllium compounds

    Pure beryllium is a steel-grey, brittle metal, the first 
element of the second group (alkaline earths) and the third element 
of the first period of the periodic table.  Its compounds are 

    Synonyms, trade names, and the chemical formulae of pure 
beryllium and some of its compounds are given in Table 1. 

2.1.2  Impure beryllium compounds

    Impure beryllium compounds are mainly represented by the 
beryllium ores bertrandite and beryl, and numerous beryllium 
alloys, some of which are listed in Table 2. 

2.2  Physical and Chemical Properties

    Some chemical and physical data of beryllium and selected 
beryllium compounds are listed in Table 3. 

    Elemental beryllium has many unique properties (Krejci & 
Scheel, 1966; Petzow & Aldinger, 1974; Ballance et al., 1978; 
Newland, 1982; Reeves, 1986).  It is the lightest of all solid and 
chemically stable substances with an unusually high melting point.  
It has a very low density and very high specific heat (1970 kJ/(kg x 
K), 25 °C), heat of fusion (11.7 kJ/mol), sound conductance (12 600 
m/s), and strength-to-weight ratio. 

    Beryllium is lighter than aluminium, but is more than 40% more 
rigid than steel.  It also has excellent electrical and thermal 
conductivities.  The only marked adverse feature is its relatively 
high brittleness, which has restricted the use of metallic 
beryllium to specialized applications. 

Table 1.   CAS chemical names and registry numbers, synonyms, trade names and atomic or molecular formulae of pure beryllium 
and beryllium compoundsa
CAS chemical name              CAS registry number  Synonyms and trade names                     Formula
Beryllium                      7440-41-7            Beryllium-9; glucinium                       Be

Acetic acid, beryllium salt    543-81-7             Beryllium acetate; beryllium acetate normal  Be(C2H3O2)2

Hexakis[acetato-0:0]-          19049-40-2           Beryllium acetate, basic; beryllium oxide    Be4O(C2H3O2)6
 oxotetraberyllium                                   acetate

Bis[carbonato-(2-)]dihydroxy-  66104-24-3           Beryllium carbonate; beryllium carbonate,    (BeCO3)2 x Be(OH)2
 triberyllium                                        basic; beryllium oxide carbonate

Beryllium chloride             7787-47-5            Beryllium dichloride                         BeCl2

Beryllium fluoride             7787-49-7            Beryllium difluoride                         BeF2

Beryllium hydroxide            13327-32-7           Beryllium dihydroxide; beryllium hydrate     Be(OH)2

Beryllium oxide                1304-56-9            Beryllia; beryllium monoxide; Thermalox      BeO

Phosphoric acid, beryllium     13598-15-7           Beryllium phosphate; beryllium hydrogen      BeHPO4
 salt (1:1)                                          phosphate

Phenakite                      13598-00-0           Beryllium silicate; beryllium silicic acid;  Be2SiO4

Sulfuric acid, beryllium       13510-49-1           Beryllium sulfate                            BeSO4
 salt  (1:1)

Silicic acid, beryllium zinc   39413-47-3           Zinc beryllium silicate                      Exact composition unknown or
salt                                                                                              undetermined
a Adapted from:  IARC (1980).
Table 2.  CAS chemical names and registry numbers, synonyms, trade names, beryllium content and 
molecular formulae of beryllium ores and alloysa
CAS chemical     CAS         Synonyms and trade names    Composition         Formula
name             registry                 
Bertrandite      12161-82-9  Bertrandite;                42.1 % BeO;         4BeO x 2SiO2 x H2O
[Be4(H2Si2O9)]               beryllium silicate          50.3 % SiO2; 
                             hydrate                     7.6 % water
Beryl            1302-52-9   Beryl ore; beryllium        10-13 % BeO;        3BeO x Al2O3 x 6SiO2
[Be3(AlSi3O9)2]              aluminium silicate;         16-19 % Al2O3;
                             beryllium alumino-          64-70 % SiO2
                             silicate                    1-2 % alkali metal 
                                                         oxides; 1-2 % iron 
                                                         and other oxides
Aluminum         12770-50-2  Beryllium-aluminium         62 % Be;            -
alloy, Al, Be                alloy; alumin(i)um-         38 % Al
                             beryllium alloy; Lockalloy
Copper alloy,    11133-98-5  Beryllium-copper-           0.3-2.0 % Be;       -
Cu, Be                       alloy; beryllium            96.9-98.3 % Cu;
                             copper                      0.2 % min. Ni
                                                         and Co; 0.6 % max.
                                                         Ni, Fe, and Co;
Nickel alloy,    37227-61-5  Beryllium nickel            2-3 % Be;           -
Ni, Be                       alloy; nickel-              up to 4 %
                             beryllium alloy             other additives
                                                         rest: Ni
a Adapted from:  IARC (1980).

Table 3.  Physical and chemical properties of beryllium and selected beryllium compoundsa
Chemical name  Atomic/    Melting-      Boiling-   Density  Crystal system      Solubility
               molecular  point (°C)    point      (g/cm3)        
               mass                     (°C)      
Beryllium      9.01       1278 ± 5      2970       1.85     alpha-close-packed  insol. cold H2O;
                                        (5 mm Hg)  (20 °C)  hexagonal,          sl. sol. hot H2O;
                                                            beta-body-centred   sol. dil. acids
                                                            cubic               and alkalies

Beryllium      127.10     300           -          -        plates              insol. cold H2O, ethanol
acetate                   (dec.)                                                and other common organic 
                                                                                solvents; slow hydrolysis 
                                                                                in boiling-water
Beryllium      79.92      405           520        1.899    needles             very sol. H2O, ethanol
chloride                                           (25 °C)                      and diethyl ether;
                                                                                sl. sol. benzene and 

Beryllium      47.01      544           1160       1.986    amorphous           very sol. H2O; sol. 
fluoride                  (800, subl.)             (25 °C)                      H2SO4 and ethanol

Beryllium      43.03      -             -          1.92     powder or           very sl. sol. H2O and 
hydroxide                                                   crystals            dil. alkali; sol. hot
                                                                                conc. NaOH and acids
Beryllium      133.03     60            -          -        deliquescent        very sol. H2O and
nitrateb                                                    crystalline mass    alcohol

Beryllium      25.01      2530 ± 30     3900       3.01     hexagonal           0.2 mg/litre H2O; sol.
oxide                                                                           conc. H2SO4

Beryllium      105.07     550-600       -          2.443    -                   insol. cold H2O; 
sulfate                   (dec.)                                                converted to 
                                                                                tetrahydrate in hot water

Beryllium      177.14     100           400        1.713    tetrahedric         425 g/litre H2O; insol.
sulfate                   (-2H2O)       (-4H2O)             crystalls           ethanol; sl. sol. conc.
tetrahydrate                                                                    H2SO4
a Adapted from:  IARC (1980), unless otherwise specified.             b Windholz (1976).
conc. = concentrated; dec. = decomposition; dil. = dilute; insol. = insoluble; sl. = slightly; 
sol. = soluble; subl. = sublimation.
    Beryllium occurs naturally only as the 9Be isotope; 4 unstable 
isotopes with mass numbers of 6, 7, 8, and 10 have been identified.  
Because of its low atomic number, beryllium is very permeable to 
X-rays.  The neutron emission upon alpha-bombardment is the most 
important of its nuclear physical properties, and beryllium can be 
used as a neutron source.  Moreover, its low neutron absorption 
properties and its high-scattering cross-section determine its 
characteristics as a suitable moderator and reflector of structural 
material in nuclear facilities; while most other metals absorb 
neutrons from the fission of nuclear fuel, beryllium atoms only 
reduce the energy of such neutrons and reflect them back into the 
fission zone. 

    The chemical properties of beryllium differ considerably from 
those of the other alkaline earths, but it has a number of chemical 
properties in common with aluminium (Krejci & Scheel, 1966; Petzow 
& Aldinger, 1974; Reeves, 1986).  Beryllium shows a very high 
affinity for oxygen; on exposure to air or water vapour, a thin 
film of beryllium oxide (BeO) forms on the surface of the bare 
metal, providing the metal with a high resistance to corrosion.  
Like aluminium, beryllium oxide (BeO) is amphoteric.  The very 
stable surface film also renders the metal resistant to water and 
cold oxidizing acids.  Dichromate in water enhances this resistance 
by forming a protective film of chromate, similar to that formed on 
aluminium.  In powder form, beryllium is readily oxidized in moist 
air and burns, because of the high entropy of formation of BeO 
(23 x 103 kJ/kg), with a temperature of about 4500 °C, when ignited 
in oxygen. 

    Beryllium powder reacts with fluorine at room temperature, and 
with chlorine, bromine, iodide, sulfur, and the vapour of selenium 
or tellurium to a significant extent only at elevated temperatures 
(Petzow & Aldinger, 1974).  From about 900 °C, nitrogen and ammonia 
react violently with beryllium to form beryllium nitride (Be3N2).  
No reaction takes place with hydrogen, even at high temperatures.  
Melted beryllium reacts with most oxides, nitrides, sulfides, and 
carbides.  Because of its amphoteric character, beryllium is 
dissolved by dilute acids and alkalis. 

    Cationic beryllium salts are hydrolysed in water and react to 
form insoluble hydroxides or hydrated complexes at pH values 
between 5 and 8, and beryllates above a pH of 8 (Reeves, 1986). 

    Beryllium oxide ("beryllia") is a colourless crystalline solid 
or an amorphous white powder with an extremely high melting point, 
high thermal conductivity, low thermal expansion, and high 
electrical resistivity.  It can either be moulded or applied as a 
coating to a metal or other base; through the process of sintering 
(1480 °C), a hard compact mass with a smooth glassy surface is 
formed (Krejci & Scheel, 1966).  The ceramic properties of sintered 
beryllium oxide make it suitable for the production or protection 
of materials used at high temperatures in corrosive environments. 

    A detailed review of the properties of beryllium compounds is 
given by Krejci & Scheel (1966). 

    The use of beryllium in alloys is based on a combination of 
outstanding properties that are conferred on other metals (Petzow & 
Aldinger, 1974).  Low density combined with strength, high melting 
point, resistance to oxidation, and a high modulus of elasticity 
make beryllium alloys suitable as light-weight materials that must 
withstand high acceleration or centrifugal forces.  Their 
advantages over steel include greater resistance to corrosion, 
higher electrical and thermal conductivities, greater strength, and 
non-magnetic and non-sparking characteristics.  Magnesium alloys 
containing 0.1% beryllium have a markedly reduced risk of 

    Most metals form very brittle intermetallic compounds with 
beryllium.  This and the low solubility of most elements in solid 
beryllium are the reasons that beryllium-rich alloys have not 
played a significant role.  The only alloy with a high beryllium 
content is lockalloy containing 62% beryllium and 38% aluminium.  
Lockalloy has a high modulus of elasticity and low density with 
reasonable ductility.  Aluminium does not form beryllides.  Other 
alloys contain up to 3% beryllium (Petzow & Aldinger, 1974; IARC, 

    Of the intermetallic compounds, the beryllides of niobium, 
tantalum, titanium, and vanadium are gaining interest in the 
aerospace industry (Stokinger, 1981).  Their properties include 
high strength at elevated temperature and good thermal conductivity 
and oxidation resistance, combined with  densities that are lower 
than those of refractory metals and many ceramics.  The most 
adverse feature of beryllides is their limited plastic 
deformability (Walsh & Rees, 1978). 

2.3  Analytical Methods

    Methods for sampling, sample preparation, and the determination 
of beryllium have been reviewed by Drury et al. (1978) and Delves 
(1981).  Since a detailed review of all the analytical procedures 
is beyond the scope of this document, only a brief overview is 
provided, including a summary of methods for the sampling and 
determination of beryllium in various matrices (Table 4). 

2.3.1  Sampling procedure and sample preparation  Sampling

   Since most environmental samples contain only trace amounts of 
beryllium, the proper collection and treatment of samples, before 
analysis, is essential. 

    Beryllium in air is sampled by means of high-volume samplers 
using low-ash cellulose fibre, cellulose ester, or fibreglass 
papers as filters for non-volatile contaminants, and liquid- or 
solid-filled scrubbers or cold traps to collect volatile forms of 
beryllium.  In the USSR, air sampling is performed on filters made 
of polyvinyl-chloride fibres plunged in filter-supporters (Izmerov, 

Table 4.  Analytical methods for beryllium and beryllium compounds
Medium      Sampling method                    Analytical method   Detection limit   Comments                    Reference
Air         Collect particulates with glass    Gas chromatography  0.04 pg/sample    No interference with        Ross & Sievers
            fibre filter; digest ashed filter  with electron-                        several other metals;       (1972)
            in boiling HCl and HNO3 refluxing  capture detection                     relatively rapid
            for 3 h; add EDTA-buffer solution                                        (40 min); relatively
            and NaOH to pH 5.5-6.0; add                                              inexpensive chromatograph;
            benzene solution of trifluoro-                                           applicable for routine
            acetylacetone; decant chelate;                                           analysis of ultratrace
            wash with NaOH                                                           concentrations (0.1 ng/m3) 
Air         Ash glass fibre filter strips;     Optical emission    5.3 µg/ml                                     Scott et al.
            add HNO3/HClO4 containing indium   spectrometry                                                      (1976)
            and yttrium; reflux; concentrate; 
            add HNO3; centrifuge; add LiCl2 

Air         Dissolve glass fibre filter in     Atomic absorption   2.5 ng/m3                                     Zdrojewski et
            hydrofluoric acid; add HNO3;       spectrophotometry                                                 al. (1976)
            boil; dilute                       Graphite furnace    0.05 ng/m3
                                               atomic absorption

Air         Extract filter with H2SO4; add     Spectrophotometry   1 ng/ml sample    Inexpensive                 Mulwani & Sathe
            chrome Azurol S, gum arabic        (605 nm)                                                          (1977)
            solution and EDTA; adjust to pH 
            2; add cetylpyridinium bromide 
            and hexamine solution; adjust to 
            pH 5

Air         Collect particles on filter;       Emission spectro-   3.6 ng/filter     Rapid, near real-time       Cremers &
            no sample preparation required     scopy using laser-  (32 mm diameter,  method (3-5 min); due to    Radziemski
                                               induced breakdown   for particles     particle size dependence    (1985)
                                               spark               0.5-5 µm in       and interferences, only
                                                                   diameter)         semi-quantitative

Air        Pass air through mixed cellulose    Graphite-furnace    5 ng/sample       Identical with official     IARC (1986)
           ester membrane filter via personal  atomic absorption                     NIOSH method; suitable
           sampling pump; digest filter in     spectrophotometry                     for working range 0.5-10
           HNO3/H2SO4; evaporate to dryness;                                         µg/m3 for a 90-litre air
           dissolve in 2%-NaOH/3%-H2SO4                                              sample

Table 4.  (contd.)
Medium      Sampling method                    Analytical method   Detection limit   Comments                    Reference
 Biological samples
Urine       Add HNO3 and heat to dryness;      Atomic absorption   2 µg/litre                                    Bokowski (1968)
            concentrate by adding NH4OH to     spectrometry,                                              
            pH 1.5, EDTA, acetylacetone,       nitrous oxide-
            NH4OH to pH 7; separate in         acetylene flame
            funnel; centrifuge; draw off 
            lower layer 

Organic     Digest sample by low temperature   Gas chromatography  10 pg/sample      Suitable for trace levels   Kaiser et al.
materials   ashing or pressure decomposition   with electron-      (< 1 g)          in limited amounts of       (1972)
(blood,     with HNO3/HF in teflon tube;       capture detection                     organic materials                  
tissue,     eliminate interfering elements                                           
food,       with EDTA; add trifluoroacetyl-
sewage,     acetone in benzene; concentrate
mud, etc.   by evaporation

Organic     Digest sample in teflon tube       Flameless atomic    0.6 µg/litre                                  Stiefel et al.
materials   under pressure; add EDTA - and     absorption          (for 1-ml urine                               (1976)
(blood,     acetyl acetone; separate Be-       spectrometry;       sample)
muscle,     complex by liquid-liquid           graphite tube                  
urine,      extraction with benzene            treated with  
etc.)                                          ZrOCl2 to increase 

Organic     Wet-ash dried tissue in HNO3/      Fluorescence        Not specified     Used to determine           Wicks & Burke
materials   HClO4 in platinum dish; add EDTA   spectrometry                          Standard Reference          (1977)
            and NH4OH to pH 7-8; add                                                 Materials (SRM)
            acetylacetone; extract with
            chloroform; add cyclohexane-
            diammine-tetraacetic acid and 
            2-hydroxy-3-napthoic acid reagent

Biological  Digest sample in HNO3/HClO4;       Graphite-furnace    1 µg/kg                                          Hurlbut (1978)
tissues     evaporate; dissolve in HNO3        atomic absorption                               
(hair,      containing lanthanum               spectrometry

Table 4.  (contd.)
Medium      Sampling method                    Analytical method   Detection limit   Comments                    Reference
 Biological samples (contd.)
Urine       Add HNO3 containing lanthanum      Graphite-furnace     0.01 µg/litre    Lanthanum enhanced signal   Hurlbut (1978)
            or add HNO3 and excess NH4OH;      atomic absorption                     and masked various cations         
            centrifuge; decant solution; heat  spectrometry                                  

Lung        Digest dried sample in HNO3/       Graphite-furnace     Not specified;   Accuracy proved with        Baumgardt et
tissue      HClO4; heat to dryness and         atomic absorption    reported range:  reference material and by   al. (1986)
            dissolve residue in HNO3           spectrometry         0.002-0.03 µg/   comparing with other               
                                                                    g dry weight     analytical methods
Fresh       Acidify with HNO3 to stabilize     Graphite-furnace     0.06 µg/litre    Used to analyse Standard    Epstein et al.
water       solution                           atomic absorption                     Reference Material          (1978)
                                               Graphite-furnace     2 µg/litre
                                               atomic emission

Sea water   Acidify with HCl; add              Gas chromatography   18 pg/kg         Precision: 5.5% at          Measures & 
            trifluoroacetylacetone; extract    with electron                         180 pg/kg                   Edmond (1982)
            beryllium complex with benzine     capture detection   
    Water samples should be collected in borosilicate glass or 
plastic containers.  It is important to adjust the pH to 5, or 
below, to prevent losses due to adsorption of beryllium on the 
surface of containers.  Particulate matter should be filtered out  
and analysed separately. 

    Urine samples are also acidified and can be preserved by adding 
a 37% formalin solution (Keenan & Holtz, 1964).  Precautions must 
be taken to avoid contamination of the urine sample during 
collection at the work-place.  Animal tissues and vegetable matter 
can also be preserved by adding formalin, or by cooling.  
[Formaldehyde is irritant, may cause sensitization, and is a 
possible human carcinogen.]  The use of formalin is discouraged in 
multielemental analyses, as this preservative contains large 
amounts of contaminants.  Instead, immediate freezing of the 
samples and storage below -15 °C is recommended (Katz, 1985).  Sample decomposition

    Organic matter, including air particulate filters, must be 
destroyed to free the beryllium contents.  This is accomplished, by 
wet digestion using different mixtures of nitric, sulfuric, and 
perchloric acid, or by dry ashing. 

    The NIOSH method for the determination of beryllium in air 
involves the digestion of cellulose ester membrane filters in a 
mixture of nitric and sulfuric acids (NIOSH, 1984). 

    Soft tissue and small bone samples can be decomposed by 
covering the sample with concentrated nitric acid and repeatedly 
heating to dryness.  The dried (400 °C) residue can then be 
analysed.  Large bone samples are dried to constant weight at 
105 °C and dry ashed in a muffle furnace by raising the temperature 
gradually to 500 °C and heating for several hours.  The ash residue 
is extracted with hydrochloric acid (Drury et al., 1978). 

    Kingston & Jassie (1986) described the use of microwave energy 
for the acid digestion of organic samples as a time-saving and 
reliable method.  Separation and concentration

    Several techniques are used to concentrate or separate 
beryllium from interfering elements, prior to analysis (Drury et 
al., 1978).  Precipitation of beryllium as the phosphate, 
hydroxide, or organic complex is only recommended for the  
separation of macro quantities of beryllium from small amounts of 
impurities.  Alternatively, it can be coprecipitated with calcium, 
manganese, titanium, and iron phosphates, and with aluminium and 
iron hydroxides.  However, in both cases, considerable losses may 

    In contrast to precipitation, solvent extraction can be used 
for micro quantities of beryllium.  Organic solvents, such as 
benzene, chloroform, or carbon tetrachloride, containing a 

beryllium complexing agent, are added to aqueous solutions in 
which cationic impurities have been complexed with 
ethylenediaminetetraacetic acid.  The latter does not complex 
beryllium.  After separating the two solvents, the organic phase, 
which contains the beryllium, is either further processed or 
directly used in analysis (Drury et al., 1978). 

    Interfering substances can also be removed by ion exchange 
techniques, using either cation or anion exchangers, and by 
electrolysis with a mercury cathode. 

2.3.2  Detection and measurement

    Older methods used up to the 1960s included spectroscopic, 
fluorometric, and spectrophotometric techniques.  The main 
deficiency of spectrophotometric methods lies in the non-
specificity of the complexing agents used to form coloured 
complexes with beryllium.  The limit of detection with these 
methods is 100 ng Be/sample (Fishbein, 1984).  The fluorometric 
method, which is based on fluorescent dyes, preferably morin, has a 
very low limit of detection of 0.02 ng Be/sample; its sensitivity 
is only exceeded by that of the gas chromatographic method.  
However, fluorometry  may  be subject to many errors, unless  
several time-consuming and cumbersome processing steps are applied 
prior to analysis.  Emission spectroscopy is the most satisfactory 
method, in terms of specificity and sensitivity.  Thermal or 
electrical excitation of the samples, which must be highly 
concentrated, is accomplished by the use of a direct or alternating 
current arc, and alternating current spark, with limits of 
detection in the range of 0.5 - 5.0 ng Be/sample (Drury et al., 
1978; Fishbein, 1984). 

    Atomic absorption spectrometry is a rapid and very convenient 
method for the analysis of environmental samples.  The limit of 
detection for the flame technique is 2 - 10 ng/ml, or lower when 
pre-analysis concentration is employed (Bokowski, 1968).  The 
flameless method is much more sensitive.  Hurlbut (1978) achieved 
detection limits of 1 ng/g for faecal, hair, and fingernail samples 
and of 0.01 ng/ml for urine samples.  Addition of lanthanum was 
found to enhance the absorption signal and eliminate interference 
by various cations.  Stiefel et al. (1980b) provided a detection 
limit of 0.01 ng/g for immunoelectrophoretic blood fractions.  
Using graphite-furnace atomic absorption spectrophotometry, the 
NIOSH procedure for the determination of beryllium in air is 
recommended for a working range of 0.05 - 1.0 µg/sample or 
0.5 - 10.0 µg/m3 of air for a 90-litre sample (NIOSH, 1984). 

    Inductively coupled plasma atomic emission spectrometry has 
been introduced to determine beryllium directly in a variety of 
biological and environmental matrices (Schramel & Li-Qiang, 1982; 
Wolnik et al., 1984; Awadallah et al., 1986; Caroli et al., 1988).  
This method is superior to the previous method, because of its high 
sensitivity and low level of interferences. 

    Owing to its high sensitivity and specificity, gas 
chromatography is also used for determining beryllium in 
environmental and biological media, particularly at ultratrace 
levels.  To convert beryllium into a volatile form, it is commonly 
chelated with trifluoroacetylacetone and injected into the 
chromatographic column.  Using an electron-capture detector, Taylor 
& Arnold (1971) determined beryllium in human blood with a 
detection limit of 0.08 pg Be/sample.  When combined with mass 
spectrometry, sensitivities in the range of 0.04 - 10 pg Be/sample 
were achieved (Wolf et al., 1972).  Ross & Sievers (1972) developed 
a routine method for environmental air analysis.  At a limit of 
detection of 0.04 pg Be/sample, beryllium concentrations in the 
range of 0.49 - 0.6 ng Be/m3 could be determined.  Because of its 
carcinogenic properties, a safer alternative to benzene should be 
considered as a solvent for trifluoroacetylacetone. 

    In the USSR, a photometric method is used to determine 
beryllium in the air, with a sensitivity of 0.005 µg/sample 
(Krivorutchko, 1966).  Using gas chromatography, a sensitivity of 
1.5 x 10-5 µg/sample is achieved (Yavorovskaya & Grinberg, 1974).  
By successive treatment of the samples with water, 5% HCl, and 
fusing with potassium fluoride, the differential determination of 
water-soluble salts, beryllium metal, and its oxide is possible 
(Naumova & Grinberg, 1974). 

    Other analytical techniques, such as polarography, enzyme 
inhibition, and various types of activation techniques, have been 
used, but do not play a major role in routine analysis (Drury et 
al., 1978).  Laser ion mass analysis is a promising technique for 
the identification of beryllium in tissue sections (Jones Williams 
& Kelland, 1986).  Cremers & Radziemski (1985) used the laser-
induced spark technique to develop a near real-time method for 
monitoring airborne beryllium concentrations. 

3.1 Natural Occurrence

    Beryllium is the 35th most abundant element in the earth's 
crust, with an average content of about 6 mg/kg (Mason, 1952).  It 
occurs in rocks and minerals at concentrations of between 0.038 and 
11.4 mg/kg (Drury et al., 1978).  More than 40 minerals with 
beryllium as the main constituent are known.  Most beryllium 
minerals were probably formed during the cooling of granitic 
magmas, which led to an accumulation of crystallization products, 
usually in association with quartz (Beus, 1966).  Thus, the 
beryllium content generally increases with increasing contents of 
silica and alkalis.  The most highly enriched beryllium deposits 
are found in granitic pegmatites, in which independent beryllium 
minerals crystallize (Wedepohl, 1966). 

    Only two beryllium minerals are of economic significance.  
Beryl, an aluminosilicate, is mined in Argentina, Brazil, China, 
India, Portugal, the USSR, and in several countries of southern and 
central Africa (US Bureau of Mines, 1985a).  Beryl contains up to 
4% beryllium.  In its purest gem quality, it occurs as emerald 
(chromium-containing beryl), aquamarine (iron-containing beryl), 
and as some semi-precious stones. 

    Although bertrandite contains less than 1% beryllium, it became 
economically important in the late 1960s, because its processing 
to beryllium hydroxide (section 3.2) is highly efficient.  
Bertrandite, mined at Spor Mountain, Utah, USA, accounts for about 
85% of the US consumption of beryllium ore (US Bureau of Mines, 
1982).  The total world reserves of beryllium that can be recovered 
by mining are estimated at 200 000 tonnes (Petzow & Aldinger, 

    Clays and residual minerals contain most of the beryllium of 
the original rocks from which they have been formed by weathering.  
Clay soils contain between 2 and 5 mg Be/kg, while sandstones 
contain less than 1 mg/kg and limestones, much less than 1 mg/kg 
(Griffitts et al., 1977). 

    The most important source of environmental beryllium is the 
burning of coal.  It can be found in the ash of many coals at 
concentrations of about 100 mg/kg (Griffitts et al., 1977).  
Globally, coals contain average concentrations of between 1.8 and 
2.2 mg/kg dry weight (US EPA, 1987).  Coal samples from Australia, 
the Federal Republic of Germany, Norway, Poland, the United 
Kingdom, USA, and USSR showed concentrations of between < 5 and 
15 mg Be/kg (Lövblad, 1977).  Mineral oils contain up to 100 µg 
Be/litre (Drury et al., 1978).  The occurrence of beryllium in coal 
and mineral oil is most probably the result of beryllium 
accumulation in the precursor plants. 

    The beryllium contents of natural waters and unpolluted air are 
very low (Fishbein, 1981) (section 5.1.1). 

3.2  Man-Made Sources

3.2.1  Production levels and manufacture  Production levels

    Beryllium production started in some industrialized countries 
around 1916 (Petzow & Aldinger, 1974).  In the early 1930s, it 
gained commercial importance following the discovery that 
beryllium-copper alloys were extraordinarily hard, resistant to 
corrosion, non-magnetic, did not spark, and withstood high 
temperatures.  In addition, because of its nuclear and thermal 
properties and high specific modulus, beryllium metal proved 
attractive for nuclear and aerospace applications, including 
weapons.  This is the main reason that reliable data on the 
production and consumption of beryllium are scarce and incomplete.  
Moreover, considerable fluctuations in beryllium supply and demand 
result from sporadic government programmes in armaments, nuclear 
energy, and aerospace.  For example, the beryllium demand in the 
USA, created by the programme for the development of the atomic 
bomb (Manhattan Project), was about equivalent to the total world 
demand up to 1940 (Newland, 1982). 

    World production, excluding the USA, parallelled the 
fluctuations of the beryllium market with 222 tonnes produced in 
1965, 320 tonnes in 1969, and 144 tonnes in 1974.  Data on US 
production are now available and the world production of beryllium 
can be characterized as shown in Table 5.  Including its production 
from bertrandite, the USA appears to be the world's largest 
producer of beryllium raw materials.  Estimated world production of 
beryllium minerals was between 8873 and 10335 tonnes in the period 
1980 - 84, which corresponds to between 355 and 413 tonnes of 

Table 5.  World mine production of beryllium (tonnes)a
Country                    1980   1981   1982   1983   1984
Argentina                  1.4    0.3    0.3    1.1    0.7
Brazil (exports)           24.2   37.6   46.8   55.2   55.2
Madagascar                 0.4    0.4    0.4    0.4    0.4
Mozambique                 0.9    0.8    0.7    0.7    0.7
Portugal                   0.8    0.8    0.8    0.8    0.8
Rwanda                     4.8    2.6    3.0    1.4    1.6
South Africa, Republic of  -      5.4    2.6    1.0    -
USA                        298.0  293.4  218.0  266.6  241.2
USSR                       80.0   80.0   80.0   84.0   84.0
Zimbabwe                   0.4    1.8    2.3    2.2    2.2
Total                      410.9  423.1  354.9  413.4  386.8
a Adapted from:  US Bureau of Mines (1985a).  Data calculated from 
  beryl ore production figures assuming a beryllium content of 4%.
    Production industries exist only in Japan, the USA, and the 
USSR.  In other countries, the imported pure metal, alloys, or the 
ceramic beryllium oxide are processed to end-products (Preuss & 
Oster, 1980). 

    The doubling of capacity for beryllium-copper strip has been 
reported by one US producer, to meet the increasing use of this 
material in electronic devices (US Bureau of Mines, 1985a).  Demand 
for beryllium was expected, in 1986, to increase at an average 
annual rate of about 4%, up to 1990 (US Bureau of Mines, 1986).  Manufacturing process

    The first step in the production of pure beryllium metal or 
beryllium compounds involves the extraction of a concentrate of 
crystals of beryllium ores by manual selection or, where conditions 
warrant, by mechanized mining methods (US Bureau of Mines, 1985b). 

    Two commercial methods are used to process beryl to beryllium 
hydroxide (Petzow & Aldinger, 1974; Stokinger, 1981; Reeves, 1986).  
In the fluoride process, beryl is sintered together with sodium 
silicofluoride, or the less expensive sodium fluoroferrate, at 
700 - 800 °C to convert beryllium oxide to a water-soluble salt 
(Na2BeF4).  This is then leached with water and precipitated from 
the purified solution with caustic soda as beryllium hydroxide.  

    The sulfate process involves the alkaline or heat processing of 
beryl and addition of strong sulfuric acid to the fused, quenched, 
and ground minerals to extract the sulfates of beryllium, 
aluminium, and other impurities.  Following purification of this 
solution the beryllium sulfate (BeSO4) is precipitated as the 

    A less complicated procedure has been developed to process the 
bertrandite ore.  The so-called SX-carbonate-process makes caustic 
pretreatment redundant and involves the direct leaching of 
beryllium sulfate with sulfuric acid and subsequent precipitation 
of beryllium hydroxide, which has a comparable high degree of 
purity (Petzow & Aldinger, 1974). 

    Beryllium hydroxide is the starting material for the production 
of beryllium, beryllia, and beryllium alloys.  For further 
processing, it is ignited to form the oxide (BeO) or converted to 
the fluoride (BeF2).  By means of the thermal reduction of BeF2 
with other metals, mainly magnesium, beryllium metal is obtained, 
which can be further processed by furnace, by electrolytic 
refining, or by powder-metallurgical techniques. 

    The commercial manufacture of copper-beryllium alloys, which 
are the most important beryllium alloys, involves melting together 
virgin copper scrap, pure cobalt or a copper-cobalt master alloy, 
and a copper-beryllium master alloy containing about 4% beryllium 
(Ballance et al., 1978).  The copper-beryllium master alloy is 
produced by an arc-furnace method in which beryllium oxide is 
reduced by carbon, in the presence of molten copper.  Emissions during production and use

    The emissions of atmospheric beryllium in the USA are 
summarized in Table 6.  Natural emissions are negligible compared 
with man-made emissions.  At present, coal combustion in power 
plants is a main source of beryllium emission.  The application of 
advanced dust emission control techniques could help to cut 
beryllium emissions considerably.  Because of the lack of data, 
beryllium emissions into the atmosphere, resulting from the 
military use of beryllium, cannot be accounted for.  Although the 
contribution of metallurgical sources to the overall beryllium 
pollution is negligible (Table 6), locally elevated ambient 
concentrations are likely to result from beryllium emissions during 
production and processing, particularly in case of insufficient 
control measures.  Sources are beryllium extraction plants, ceramic 
plants, foundries, machine shops, propellant plants, incinerators, 
rocket-motor test facilities, and open-burning sites for waste 
disposal (US EPA, 1973). 
Table 6.  Atmospheric beryllium emissions from different sources in the USA
Source                                  Total US       Emission  Annual         Percentage
                                        production     factor    emission       of total 
                                        (tonnes/year)  (g/tonne) (tonnes/year)  emission
Natural sourcesa
Windblown dust                          8.2 x 106      0.6       5              2.48
Volcanic particles                      0.41 x 106     0.6       0.2            0.10
Total emission from natural sources                              5.2            2.58
Man-made sources
 Beryllium production and processing: 
Mining                                                           negligiblec
Ore processinga                         8 x 103        37.5      0.3            0.15
Be production                                                    negligiblec
Ceramic productionc                     32             450       0.014          0.01
Cast iron productionc                   -              -         3.6            1.79
Production of Be alloys and compoundsb  -              -         5              2.48
Total emission from beryllium production                         8.914          4.43
 Combustion of fossil fuels
Coala                                   640 x 106      0.28      180            89.46
Fuel oila                               148 x 106      0.048     7.1            3.53
Total emission from combustion of fossil fuels                   187.1          92.99
Total beryllium emission from all sources                        201.2          100.00
a Data from US Environmental Protection Agency (1987).
b Data from Drury et al. (1978). 
c Data from US Environmental Protection Agency (1971).
    Beryllium extraction and production plants emit many forms of 
beryllium including beryl ore dust, beryllium and beryllium oxide 
acid fume and dust, and a slurry of Be(OH)2 and (NH4)2BeF4 (US EPA, 
1973).  There are no recent data on emissions during the production 
and processing of beryllium; according to earlier data from the US 
EPA (1971), about 5 kg of beryllium for every 1000 tonnes of 
beryllium processed are released into the ambient atmosphere during 
beryllium production, resulting in a total emission of 6 kg in the 
USA in the year 1968 (Drury et al., 1978).  About 0.45 kg of 
beryllium in the form of BeO-containing dusts, fumes, and mists are 
emitted for every tonne processed to beryllia ceramics (US EPA, 
1971), amounting to only 14.4 kg of the total US emission from this 
source in 1968, assuming a production of 32 tonnes of beryllia 
ceramics (10% of total beryllium demand in 1968).  Major emissions 
result from the cast iron production and fabrication of beryllium 
alloys and compounds (Table 6).  Beryllium emissions into the US 
atmosphere from production-related sources added up to about 8.6 
tonnes in 1968.  This is only about 4.4% of the overall emission 
from all sources. 

    As outlined in section 3.3, considerable amounts of beryllium 
are used for military purposes, e.g., as rocket propellant.  During 
test flights, a major part of the beryllium will be released to the 
atmosphere (Drury et al., 1978).  Disposal of wastes

    Most of the beryllium scrap is resold to the producer; 
recycling of most end-products is not worthwhile, because of their 
small size and, usually, their low beryllium content (Griffitts et 
al., 1977).  They are either discarded along with other solid 
wastes or salvaged for the copper in the alloy.  In one instance, 
beryllium-copper dust was dumped on to railroad tracks (OSHA, 
Personal communication, 1989). 

    The major portion of beryllium waste results from pollution 
control measures (Powers, 1976).  The beryllium-containing dust 
retained in scrubbers, electric sleeve filters, and multi-staged 
purification devices is recycled into the production process, as 
are liquid and solid wastes from hydrometallurgical and other 
processes (Izmerov, 1985).  Waste waters must be filtered before 
discharging into the receiving waters.  High efficiency is achieved 
in sewage purification using filters made of "lavsan" to remove 
metallic beryllium particles (Bobrischev-Pushkin et al., 1976). 

    Liquid, solid, or particulate waste that is too dilute to 
recycle is buried in water-proof tailings ponds or in plastic 
containers sealed in metal drums (US EPA, 1973).  Often these 
wastes are first burned to produce the chemically inert beryllium 
oxide.  The exhaust gases are scrubbed to retain particulates.  The 
disposal of scrap beryllium propellant involves underground 
detonation and subsequent filtering of exhaust gases through 
particulate air filters. 

    The flue gas cleaning system of industrial waste incineration 
plants is designed to meet the national emission standards.  For 
instance, according to the Clean Air Act of the Federal Republic of 
Germany, the sum of the emissions of beryllium, benz( a)pyrene, and 
dibenzanthracene must not exceed 0.1 mg/m3 in the flue gases of 
hazardous waste incinerators.  Test runs showed an average 
beryllium emission of 0.02 mg/m3 (STP) (Erbach, 1984). 

3.2.2  Coal and oil combustion

    A major source of atmospheric beryllium is the combustion of 
fossil fuels, of which coal is the most important pollutant source.  
The US EPA (1987) estimated that between 10 and 30% of the 
beryllium contained in coal is emitted during the combustion 
process.  The remainder is retained by the captured fly ash.  On 
the basis of the average beryllium content of coal (1.4 mg/kg), the 
combustion of 790 x 106 tonnes of coal in the USA during 1984 
resulted in a total beryllium emission of 220 ± 110 tonnes/year, 
while the consumption of 110 x 106 tonnes of fuel oil led to a 
beryllium release of more than 7.1 tonnes.  In 1981, the total 
beryllium emission from fossil fuel combustion was 187.1 
tonnes/year or about 93% of the combined emissions from all sources 
(Table 6). 

    The emission factor is dependent on the efficiency of 
mechanical and electrostatic precipitors of power plants.  Thus, 
improved dust emission control measures will cut the emission of 
pollutants substantially.  For instance, the average efficiency of 
fly-ash collectors (electrostatic precipitators) in coal-power 
plants in the Federal Republic of Germany is assumed to be between 
97 and 99%.  Hence, only 2.1 tonnes of beryllium were calculated to 
be released into the atmosphere in 1981 from the combustion of 
about 82 x 106 tonnes of coal (Brumsack et al., 1984). 

3.3  Uses

    Some of the most current applications of beryllium are listed 
in Table 7. 

    Almost all of the beryllium produced is used as the free metal, 
in the form of its alloys, or as the oxide.  The various beryllium 
compounds are primarily used as intermediates in the preparation of 
beryllium metal or its alloys.  Zinc beryllium silicate and 
beryllium oxide were used widely in fluorescent tube phosphors, 
until this application was abandoned in 1949 because of 
considerable health hazards (Newland, 1982). 

    The main use of beryllium arises from the outstanding 
properties that it confers on other metals; about 72% of the 
beryllium produced is used in the form of beryllium-copper and 
other alloys.  About 20% is used as the free metal (Reeves, 1986) 
and beryllium oxide accounts for the remaining 8%.  In 1983, it was 
estimated that about 65% of the US consumption was in the form of 
beryllium alloys, about 15% in the oxide form, and the remainder in 
the metal form (US Bureau of Mines, 1985b). 

Table 7.   Uses of beryllium metal, beryllium alloys, and beryllium oxide as related to 
their propertiesa     
Form         Properties               Technology  Use
Beryllium    High strength-to-weight  Aerospace   Windshield frames in US space shuttles
metal         ratio                               Structural components in aeroplanes,
                                                   rockets, satellites, and space
                                                  Antennae in data-gathering satellitesc 
                                                  Turbine rotor blades      
             Heat sink                            Aircraft brakes
                                                  Heat shields for space vehicles and
             Dimensional stability                Inertial guidance systems
                                                  Other control systems 
                                                  Mirror components of satellite optical
             High heat-of-                        Rocket propellant
             combustion-to weight
             Neutron source and       Weapons     Nuclear weapons
             Moderator and reflector  Nuclear     Components of nuclear reactors
              for neutrons                                 
                                                  Nuclear fuel element as UBe13 alloyd 
                                                  Neutron reflector in high-flux test
             Transparency for X-rays  X-ray and   Windows in X-ray tubes and radiation
                                      radiation    detection devices
                                                  Coating for biological X-ray  
             Transparency for X-rays  Computer    Ultrathin foil for X-ray lithography
Beryllium-   Dimensional stability    Aerospace   Aircraft engine parts
Beryllium-   High strength; good      Electronic  Contacts
copper       electrical and thermal               Switches
alloys       conductivity                         Circuit breaker parts
                                                  Fuse clips
                                                  High-frequency connector plugs
Table 7.  (contd.)
Form         Properties               Technology  Use
Beryllium-   High strength            Mechanical  Springs
copper                                            Bearings
alloys                                            Gear parts
(contd.)                                          Camera shutters
                                                  Golf club headse
             Non-sparking                         Tools
             High strength; good      Others      Injection moulds for plastics
             thermal conductivity;                Precision castings
             dimensional stability                Diaphragms        
                                                  Welding electrodes
Beryllium-                            Aerospace   Construction materials for aircraft
aluminium                                          and spacecraftf
Beryllium-   High strength            Electronic  Springsf
copper-      Good conductivity                    Switchesf
cobalt-                                           Contactsf
alloyf,g                                          Welding electrodes and holdersg
                                      Mechanical  Bushingsg
                                                  Soldering iron tipsg
                                      Others      Nozzles for gas and oil burnersg
                                                  Plunger tips for die-casting machinesg
Beryllium-   Higher thermal           Aerospace   Aircraft and spacecraft partsh
nickel-      conductivity than        
alloy        beryllium-copper alloys  Glass       Various glass-moulding functionsf 
Beryllium-                            Electronic  Electrical connectorsf
alloy                                 Others      Springsf
                                                  Diamond drill bit matricesh
                                                  Watch balance wheelsh
Beryllium-   Facilitated castability  Dentistry   Alternatives to gold alloys used for
nickel-      High porcelain-metal                  crowns and bridgesi,k
chromium     bond strength                         

Beryllium    High thermal             Aerospace   Rocket-chamber-combustion liners
oxide        conductivity, heat                    
             capacity, and            Electronic  Electrical insulator    
             electrical resistivity               Resistor coresh         

Table 7.  (contd.)
Form         Properties               Technology  Use
Beryllium    Ceramic properties                   Integrated circuit chip carriersh 
oxide                                             Radio, laser, and microwave tubesh 
(contd.)                                          Spark plugs             
                                                  Other high-voltage electrical components 
             Moderator and reflector  Nuclear     Components of nuclear reactorsl
             for neutrons                            
             High thermal             Others      Mantels in gas lanternsm
a Adapted from:  Newland (1982), unless otherwise specified.
b Lupton & Aldinger (1983).
c Greenfield (1971).
d Stokinger (1981).
e OSHA (1989).
f Ballance et al. (1978).
g IARC (1980).
h Reeves (1986). 
i Covington et al. (1985a).
k Bencko (1989).
l Boland (1958).
m Griggs (1973).
    Most beryllium-copper alloys are used in parts that need 
extraordinary hardness, such as bushings, bearings, springs, 
electric contacts, and switches.  A more recent use is the 
manufacture of 1.8% beryllium-copper alloy golf club heads.  Other 
important applications include the manufacture of welding 
electrodes and precision casting for optical and mechanical 
recording instruments.  Non-sparking tools made of beryllium-copper 
alloys are convenient materials for use in explosive atmospheres, 
e.g., in petroleum refineries. 

    Beryllium-aluminium alloys are gaining interest for use as 
construction materials in aircraft and spacecraft technology 
(Izmerov, 1985).  Also, some intermetallic compounds of beryllium, 
particularly the beryllides of niobium, tantalum, titanium, 
vanadium, and the borides of beryllium are being considered for use 
as structural materials for space vehicles (Stokinger, 1981). 

    Beryllium-nickel alloy is used in the place of beryllium-copper 
alloy for high-temperature applications (Farkas, 1977).  It also 
has greater hardness than the copper alloy and is therefore used in 
the production of components requiring this property, e.g., watch-
balance wheels. 

    Beryllium-containing alloys are increasingly used in dentistry 
as alternatives to more expensive gold alloys.  When added to 
nickel-chromium alloys, beryllium (2% or less) facilitates 
castability and increases the porcelain-metal bond strength 

(Covington et al., 1985a).  Apart from dental prostheses, beryllium 
has also been found in the cement used to fix crowns and bridges, 
as reported by Schönherr & Pevny (1985), but no data were given. 

    The applications of beryllium metal are mainly related to its 
nuclear and thermal properties and high specific modulus 
(Greenfield, 1971; Ballance et al., 1978).  For many years, the 
major application of beryllium in the form of thin sheets, was in 
X-ray windows.  Such windows are also used in Geiger proportional 
and scintillation counters. 

    In the 1950s, beryllium and its oxide were believed to be 
promising moderator and reflector materials for nuclear reactors.  
However, because the shut-down of a graphite-moderated reactor is 
much faster and because of the high cost of beryllium, nuclear 
applications have been limited to test reactors and, probably, to 
mobile reactors, as used in nuclear submarines.  It is also assumed 
that beryllium is used as reflector material in atomic bombs.  The 
development of beryllium-based cladding material for uranium 
dioxide fuel was abandoned in the 1960s, because of the high costs 
and brittleness of beryllium, which caused tube cracking 
(Greenfield, 1971; Buresch, 1983). 

    A major application of beryllium is for aircraft and spacecraft 
structural materials where a combination of light weight, rigidity, 
dimensional stability, and good thermal characteristics is 
demanded.  The advantage of using beryllium in missiles and 
spacecraft lies in its superiority, in this respect, over any other 
metal or alloy.  For instance, basic weights of 3-stage missiles 
are reduced by 40%, compared with steel (Greenfield, 1971).  Its 
high modulus of elasticity and dimensional stability make beryllium 
an excellent material for use in aircraft and spacecraft 
instruments including inertial guidance devices and other control 
systems using gyroscopes, gimbals, torque tubes, and high-speed 
rotating elements. 

    Beryllium is also used as a heat sink for aircraft wheel brakes 
and the heat shields of re-entry space vehicles and missiles, and 
for scanning mirrors and large mirror components of satellite 
optical systems (Ballance et al., 1978). 

    Since most of these applications of beryllium are for military 
devices, no data concerning the demand for beryllium for the 
various applications are available.  There is almost a total lack 
of information on the use of beryllium powder as solid rocket 
propellant, although test flights of such rockets could contribute 
considerably to local non-occupational exposure to atmospheric 
beryllium.  It is believed that beryllium is gaining interest as an 
ideal rocket propellant in terms of high heat of combustion at low 
weight.  In these properties, it is superior to other solid and 
chemically stable substances (Reeves, 1977; Krampitz, 1980).  The 
existence of a rocket propellant industry (Fishbein, 1981) is 
indicative of the importance of beryllium for this application. 

    Owing to its high thermal conductivity and heat capacity 
combined with high electrical resistivity, beryllium oxide has 
major ceramic applications in electronics and micro-electronics, 
where it is used as an electrical insulator in parts requiring 
thermal dissipation.  Metallized beryllia is used for the removal 
of heat in semiconductor devices and integrated circuits (Walsh & 
Rees, 1978).  Its high transparency to microwaves renders beryllium 
oxide suitable for use in microwave technology (Ballance et al., 
1978).  The oxide of beryllium is also a component of mantles of 
gas lanterns, one of the rare non-industrial applications (Griggs, 

    Data concerning the fate of beryllium in the environment are 
limited.  Since the major source of atmospheric beryllium is coal 
combustion, the most prevalent chemical form is probably beryllium 
oxide, mainly bound to particles smaller than 1 µm.  The residence 
time of these particles in the atmosphere is about 10 days (US EPA, 
1987).  Beryllium returns to earth by wet and dry deposition in a 
similar manner  to other metals and on particles of comparable size 
distribution (Kwapulinski & Pastuszka, 1983). 

    During the natural processes of weathering and formation of 
sediments, beryllium resembles aluminium in that it is enriched in 
clays, bauxites, recent deep-sea deposits, and other hydrolyzate 
sediments (Newland, 1982). 

    Reactions of beryllium in solution and soil depend on the pH.  
At environmental pH ranges of 4 - 8, beryllium oxide is highly 
insoluble, thus preventing mobilization in soil.  Beryllium is 
strongly absorbed by finely dispersed sedimentary materials 
including clays, iron hydroxides, and organic substances (Izmerov, 
1985).  Thus, very little is released into ground water, during 
weathering.  If beryllium oxide is converted to the ionized salts 
(chloride, sulfate, nitrate) during atmospheric transport, 
solubility upon deposition and, hence, mobility in soils would be 
greatly enhanced, but this has not been reported in the literature. 

    Because of the low solubility of beryllium oxide and hydroxide 
at pH levels commonly found in natural waters, only small amounts 
of beryllium are found in the form of the chloride, fluoride, 
chlorocarbonate, or organic complexes (Griffitts et al., 1977). 

    If beryllium is bioavailable in the soil matrices, it can be 
assimilated by plants and, thus, enter the food chain.  Beryllium 
is classified as a fast-exchange metal, and could potentially 
interfere with the transport of nutritive metals, such as calcium, 
into eukaryotic cells (Wood & Wang, 1983).  Although there is a 
lack of data on beryllium levels in environmental organisms 
representing high trophic levels, and on the fate of beryllium in 
ecosystems, it is not believed to biomagnify within food chains to 
an extent that would imply an important pathway to the consumer. 

    From the beryllium levels found (section, it appears 
that plants take up beryllium in small amounts.  However, some 
species act as accumulators of beryllium.  Hickory trees ( Carya 
spp.) contain as much as 1 mg/kg dry weight (Griffitts, 1977).  
Nikonova (1967) found up to 10 mg/kg in several plant species in 
the South Urals (USSR).  Tundra plants (Seward Peninsula, Alaska) 
tend to accumulate beryllium from soils, if the soil content is at, 
or below, 20 mg/kg; however, above 50 mg/kg, the plants cannot 
absorb more (Sainsbury et al., 1968).  Thus, plant ash may  contain 
greater amounts of beryllium than the soil. 

    Tolle et al. (1983) investigated beryllium accumulation by 
plants grown on soil that had been treated with beryllium-
containing precipitator fly ash from a power plant.  The beryllium 
concentration in the soil was not reported.  Beryllium uptake by 
mixed-species crops of alfalfa, timothy, and oats, planted either 
in agricultural microcosms or in field plots, did not differ from 
that of control plants.  Moreover, uptake by oat grains was 
comparable to uptake by oat stalks, indicating that there was not 
any selective enrichment in the grains.  Kloke et al. (1984) 
estimated that the transfer plant/soil coefficient for beryllium 
was of the order of magnitude of 0.01 - 0.1, depending on the plant 
species and soil properties. 

    The roots of barley, bean, tomato, and sunflower plants, grown 
for 30 days in aerated nutrient solution containing undetermined 
levels of the Be7 isotope, showed a radioactivity of between 29 717 
and 66 968 cpm/g.  From the corresponding values in the leaf, stem, 
and fruit (146 - 910 cpm/g), it can be concluded that very little 
beryllium is translocated to other plant parts (Romney & Childress, 
1965).  Leaves seemed to take up more beryllium than stems or 

    As with other metals, beryllium contamination also occurs from 
the wet and dry deposition of beryllium-containing particles on the 
above-ground plant parts.  Although beryllium levels in the leaves 
of some species have been reported (section 5.1.6), there are no 
data concerning the uptake of atmospheric beryllium into leaves. 

    No data are available on the trophic transfer of beryllium in 
aquatic ecosystems. 


5.1  Environmental Levels

5.1.1  Ambient air

    The atmospheric background level of beryllium in the USA has 
previously been reported to average less than 0.1 ng/m3 (Bowen, 
1966) or 0.2 ng/m3 (Sussman et al., 1959).  In a more recent 
survey, the annual averages during 1977 - 81, at most monitoring 
stations throughout the USA, were around the detection limit of 
0.03 ng/m3 (US EPA, 1987).  This agrees with the mean values of 
0.03 - 0.06 ng/m3 found by Ross et al. (1977), at rural sites in 
the USA, using a sensitive chelation-gas chromatographic method.  
Since fossil fuel combustion contributes to the ubiquitous 
occurrence of beryllium, particularly in the highly industrialized 
northern hemisphere, these background levels reflect the overall 
pollution from this source. 

    There appears to be a considerable range of reported values for 
beryllium concentrations in urban air.  The air of over 100 cities 
in the USA, sampled in 1964 - 65, did not contain detectable 
amounts of beryllium at a detection limit of 0.1 ng/m3 (Drury et 
al., 1978).  In the 1950s, beryllium concentrations of between 0.1 
and 0.5 ng/m3 were found in major US cities, such as New York and 
Los Angeles.  The maximum level of beryllium in the air of more 
than 30 metropolitan areas was 3 ng/m3 (Chambers et al., 1955). 

    The highest 24-h level measured in a 1977 survey in Atlanta, 
Georgia, was 1.78 ng/m3.  The annual averages, at urban monitoring 
stations throughout the USA with levels exceeding 0.1 ng/m3, ranged 
between 0.1 and 6.7 ng/m3, during 1981-86 (US EPA, 1987).  Ross et 
al. (1977) reported concentrations of beryllium in air particulates 
of 0.04 - 0.07 ng/m3, at suburban sites, and 0.1 - 0.2 ng/m3, at 
urban industrial sites, in Dayton, Ohio. 

    Using flameless atomic absorption spectrophotometry, Ikebe et 
al. (1986) found an average of 0.042 ng/m3 in 76 air samples from 
17 Japanese cities, collected between 1977 and 1980.  The highest 
values were found in Tokyo (0.222 ng/m3) and in an industrial area 
in Kitakyushu (0.211 ng/m3). 

    Freise & Israel (1987) found annual mean values in Berlin 
ranging between 0.2 and 0.33 ng/m3, for sectors with different wind 

    A concentration of 0.06 ng/m3 was measured in a residential and 
office area as well as in the inner city area of Frankfurt (Federal 
Republic of Germany), whereas a concentration of 0.02 ng/m3 was 
measured in a rural area near Frankfurt (Mueller, 1979). 

    Before the introduction of control measures, atmospheric 
beryllium concentrations were extremely high in the vicinity of 
point sources.  In the vicinity of a Pennsylvania (USA) processing 
plant, a mean concentration of 15.5 ng/m3 and a maximum of 82.7 

ng/m3 were reported.  At various distances from the plant, the 
average concentrations dropped from 28 ng/m3 at 0 - 800 m to about 
6.6 ng/m3 at a distance of 1800 - 3200 m and to 1.4 ng/m3 further 
away.  During a partial plant shutdown, the beryllium level dropped 
to 4.7 ng/m3, while a complete 2-week shutdown resulted in an 
average of 1.5 ng/m3 (Sussman et al., 1959). 

    About 0.4 km from the stack of a beryllium emission source in 
the USA, the beryllium concentration in air was 200 ng/m3; however, 
at a distance of 16 km, it was below the detection limit (1 ng/m3) 
(Eisenbud et al., 1949).  The air level, 400 m from a beryllium 
extracting and processing plant in the USSR that was not equipped 
with emission control devices, averaged 1000 ng Be/m3; at 1000 m, 
it was between 10 and 100 ng/m3.  Between 500 and 1500 m from a 
mechanical beryllium-finishing plant with operational filter 
facilities, no beryllium was detected in the air (Izmerov, 1985). 

    Bobrischev-Pushkin et al. (1973, 1976) investigated the 
atmospheric air conditions around a plant for the mechanical 
treatment of beryllium.  In accordance with health rules for 
operations involving beryllium, the air emissions were subjected to 
a multi-stage purification process using PVC fibre tissue as a 
final filtering element.  In 290 air samples taken at distances of 
500, 900, 1000, and 1500 metres downwind from the plant, beryllium 
could not be detected by gas chromatography (sensitivity 1.5 x 10-5 
µg in the volume analysed). 

    Bencko et al. (1980) reported beryllium concentrations of 
between 3.9 and 16.8 ng/m3 (average 8.4 ng/m3) in the vicinity of a 
Czecho-slovakian power plant, situated at the edge of a town from 
which the non-occupationally exposed group in this study was taken. 

5.1.2  Surface waters and sediments

    Beryllium concentrations in surface waters are usually in the 
ng/litre range (Table 8).  Levels reported for Australian rivers 
ranged from not detectable to 0.08 µg/litre, with mean 
concentrations of between 0.02 and 0.03 µg/litre (Meehan & Smythe, 
1967).  Although otherwise highly polluted, samples of the rivers 
Rhine and Main (Federal Republic of Germany) contained beryllium 
only at concentrations of < 0.005 - 0.02 µg/litre, with mean 
values of 0.009 and 0.019 µg/litre, respectively (Reichert, 1974).  
Higher levels were reported in the Rhine region in 1983 - 85 (IAWR, 
1986):  the mean values at two measuring stations were around 0.1 
µg/litre, the maximum values were between 0.26 and 0.52 µg/litre.  
Durum & Haffty (1961) analysed 15 major rivers in the USA and 
Canada and found detectable amounts of beryllium in only 2 water 
samples (< 0.06 µg Be/litre and < 0.22 µg Be/litre) out of 59. 

    Beryllium levels in seawater are ten times lower than those in 
surface waters.  In the Pacific Ocean, concentrations of 0.6 
ng/litre (Merril et al., 1960) and 2 ng/litre (Meehan & Smythe, 
1967) were reported.  Data reported by Measures & Edmond (1982) 
showed that still lower concentrations can be expected.  In a 
detailed profile analysis, the concentration of beryllium has been 

shown to increase with depth.  The mixed layer, up to about 500 m, 
is characterized by a level of between 0.04 and 0.06 ng Be/litre; 
the concentrations rise through the main thermocline to levels of 
0.22 - 0.27 ng/litre (25 - 30 pmol/kg) in the deep and bottom 
waters (2500 - 5900 m).  
Table 8.   Beryllium concentrations in surface waters
Number   Surface water and                  Range           mg/litre  Reference    
of       location                                           mean    
1        Lachlan (Farbes, Australia)                        0.01      Meehan & 
1        Macquarie (Bathurst, Australia)                    0.01      Smythe (1967)
1        Nepean (Emu Plains, Australia)                     NDa
27       Woronara (Discharge Pt, Australia)  0.01-0.012     0.03
26       Woronara (Tolofin, Australia)       0.01-0.08      0.02
59       15 rivers in the USA and Canada     ND-< 0.22b     nsc       Durum & Haffty (1961)
nsc      Raw surface waters in the USA       0.01-1.22d     0.19      National Academy of 
                                                                      Sciences (1977)
nsc      River Rhine (Federal Republic of    < 0.005-0.011  0.009     Reichert (1974)
nsc      River Main (Federal Republic of     0.008-0.02      0.019 
nsc      River Rhine (Netherlands)           0.36-0.58e      0.09     IAWR (1986)
1        Pacific Ocean                       -               0.002    Meehan & Smythe
1        Indian Ocean                                        0.001    (1967)
5        Pacific Ocean                       -               0.0006   Merril et al. (1960)
nsc      Pacific Ocean, near Hawaii, depth   -               0.00004  Measures & Edmond
         40 m                                                         (1982) 
a ND = not detected.
b Detected but less than figure indicated.
c ns = not specified.
d Beryllium was detected only in 5.4% of 1577 raw surface waters.
e Range of maximum values.
    When several ground-water samples were analysed in the western 
USA, beryllium was detected in only 3 highly acidic mine waters 
(Griffitts et al., 1977).  Ground-water samples from the Federal 
Republic of Germany contained levels ranging from not detectable 
(< 0.005 µg/litre) to 0.009 µg/litre with a mean of 0.008 µg/litre 
(Reichert, 1974). 

    The beryllium contents of sediments correspond to those of soil 
samples (section 5.1.3).  Bottom sediments of lakes in Illinois, 
USA, contained 1.4 - 7.4 mg/kg (Dreher et al., 1977).  The mean 
beryllium content of Tokyo Bay and Sagami Bay sediments (Japan) was 
1.29 mg/kg (Asami & Fukazawa, 1985). 

5.1.3  Soil

    As outlined in section 3.1, beryllium is widely distributed in 
soils at low concentrations.  Geochemical surveys (e.g., US EPA 
(1987)) suggested an overall average of about 6 mg/kg for beryllium 
in the lithosphere as a whole.  More specific data (Shacklette et 
al., 1971) indicated lower levels for agricultural soils; 847 
samples collected at a depth of 20 cm throughout the USA contained 
between less than 1 and 7 mg beryllium/kg, averaging 0.6 mg/kg.  
Only 12% of the samples exceeded 1.5 mg/kg.  None were collected in 
geological areas containing large deposits of beryllium minerals.  
These areas are relatively rare, but they account for the overall 
lithospheric average of 6 mg/kg. 

    The beryllium contents of uncontaminated Japanese soils were of 
the same order of magnitude.  Asami & Fukazawa (1985) analysed over 
100 soil horizons from all over Japan and found a mean 
concentration of 1.31 mg beryllium/kg.  The beryllium contents of 
the surface soils of paddy fields ranged from 1.10 to 1.95 mg/kg 
and those of the subsoils, 0.88 - 1.95 mg/kg.  Podzol and brown 
forest soil contained between 0.01 and 2.72 mg/kg, with regional 
differences.  Mineral surface soils showed beryllium levels of 
0.27 - 1.66 mg/kg.  Beryllium distribution in the profiles of 
forest soils reflected a leaching process; in all the profiles, the 
beryllium contents generally increased with an increase in depth.  
For example, beryllium contents of a yellowish brown forest soil 
were as follows: 1.66 mg/kg in the topmost mineral layer 
(A1-horizon, 0 - 9 cm), 2.39 mg/kg in the subsoil (B2-horizon, 
17 - 30 cm), and 2.72 mg/kg in the layer below (C3-horizon, 48 - 58 
cm).  In some profiles, beryllium contents decreased again at 
deeper horizons. 

    In some small and unpopulated areas in which rocks contained 
unusually high levels of beryllium, the overlying soils also showed 
relatively high beryllium concentrations.  For instance, soils of 
the beryllium district in the Lost River Valley, Alaska, contained 
up to 300 mg beryllium/kg, with an average of 60 mg/kg (Shacklette 
et al., 1971). 

    In the Federal Republic of Germany, an allowable concentration 
of 10 mg/kg air-dried soil was proposed by Kloke et al. (1984) as a 
guideline value for arable soils. 

5.1.4  Food and drinking-water

    Only limited data concerning the beryllium contents of foods 
are available.  Meehan & Smythe (1967), using a chemical analytical 
method, found generally low levels in various food samples from New 
South Wales, Australia including:  beans, 10 µg/kg ash weight (0.07 

µg/kg fresh weight (FW)); cabbage, 30 µg/kg (0.23 µg/kg FW); eggs, 
6 µg/kg (0.05 µg/kg FW); milk, 20 µg/kg (0.17 g/kg FW); crabs, 
100 - 170 µg/kg (15.4 - 26.2 µg/kg FW); whole marine fish, 21 - 23 
µg/kg (10.6  - 10.9 µg/kg FW); fish fillets, not detectable - 40 
µg/kg (up to 1.48 µg/kg FW); and oyster flesh, 30 - 100 µg/kg 
(0.6 - 2.0 µg/kg FW). 

    Food samples from the Federal Republic of Germany, analysed 
using atomic absorption spectrometry, contained the following 
beryllium concentrations (Zorn & Diem, 1974): crispbread, 120 
µg/kg dry weight; green head lettuce, 330 µg/kg; tomatoes, 240 
µg/kg; polished rice, 80 µg/kg; and potatoes, 170 µg/kg.  Assuming 
an average moisture content of about 95% for tomatoes and lettuce, 
77% for potatoes, and 17% for rice (Franke, 1985), these values 
correspond to about 10 - 70 µg/kg, on a fresh weight basis.  
Although these levels are somewhat higher than those reported 
above, no direct comparison can be made, because of insufficient 
numbers of samples and probable differences in sensitivity of the 
analytical methods used in the studies. 

    Awadallah et al. (1986) recently published data on beryllium 
concentrations in some Egyptian crop plants, measured by 
inductively coupled plasma-atomic emission spectrometry.  The 
plants contained between 0.3 and 2.5 mg/kg dry weight.  However, 
the values reported are probably from single measurements and, 
thus, the data base is very limited. 

    Levels of 0.02 - 0.17 µg Be/litre with a mean of 0.1 µg 
Be/litre have been reported for drinking-water in the USA (National 
Academy of Sciences, 1977).  Detectable amounts were found in only 
1.1% of the samples.  According to APHA (1971), beryllium 
concentrations in US drinking-water ranged from 0.01 to 0.7 
µg/litre, with a mean of 0.013 µg/litre.  In drinking-water samples 
from the Federal Republic of Germany, beryllium concentrations 
ranged between "not detectable" (< 0.005 µg/litre) and 0.009 
µg/litre (mean 0.008 µg/litre) (Reichert, 1974).  Sauer & Lieser 
(1986) found beryllium levels of 0.025 ± 0.013 µg/litre (SD), 
0.027 ± 0.008 µg/litre, and 0.024 ± 0.007 µg/litre, respectively, 
in unfiltered, filtered (0.45 µm filter), and ultrafiltered (2 nm 
filter) drinking-water samples from Wiesbaden, Federal Republic of 
Germany.  Thus, about 95% of the beryllium is in its molecular-
dispersed form. 

5.1.5  Tobacco

    Zorn & Diem (1974) determined the beryllium contents in 3 
brands of cigarettes, using atomic absorption spectrometry.  The 
origin of the tobaccos and the number of samples analysed were not 
indicated.  The beryllium levels were 0.47, 0.68, and 0.74 
µg/cigarette.  Assuming a tobacco content of about 0.6 g/cigarette, 
the tobacco contained between 0.8 and 1.2 mg Be/kg.  Between 1.6 
and 10% of the beryllium content, or 0.011 - 0.074 µg/cigarette, 
was reported to pass into the smoke during smoking. 

5.1.6  Environmental organisms   Plants

    Apart from organisms analysed as foodstuffs, only few data 
exist for beryllium levels in terrestrial or aquatic organisms. 

    The beryllium contents of plant samples are generally below 1 
mg/kg dry weight.  Exceptions are some plants that concentrate 
beryllium from soils (Griffitts et al., 1977).  As reported in 
section 4.2, hickory trees contain as much as 1 mg beryllium/kg dry 
weight or 30 mg/kg in plant ash.  Nikonova (1967) analysed 45 plant 
species in the Southern Urals (USSR) and detected beryllium in 
samples of wood, bark, twigs, and leaves of 23 species in 
concentrations of up to 0.001% (10 mg/kg).  While many samples 
contained only traces of beryllium, samples of birch ( Betula 
 verrucosa Ehrh.) and larch trees ( Larix sukaczewii Dylis.) showed 
elevated concentrations.  The use of bioaccumulators as indicators 
of exploitable ore deposits was discussed by Nikonova (1967). 

    Conifers usually contain less than 0.1 mg/kg dry weight (< 1 
mg/kg in the ash), while dogwood ( Cornus spp.) and other broad-
leaved trees and shrubs contain more than conifers.  However, 
Griffitts et al. (1977) did not give any values. 

    Investigating the movement of elements into the atmosphere from 
coniferous trees in the subalpine forests of Colorado and Idaho 
(USA), Curtin et al. (1974) found beryllium concentrations ranging 
from traces up to 1 mg/kg in the ash of needles, twigs, and exudate 
residues.  This is well below 0.1 mg/kg on a dry weight basis.  The 
corresponding soil contents were on average 1.4 - 2.7 mg/kg ash 
weight (mulch layer), 2.1 - 5.9 mg/kg (topmost mineral layer), and 
1.9 - 5.4 mg/kg (subsoil). 

    Dittmann et al. (1984) used leaves of poplar trees  (Populus 
 nigra) for monitoring beryllium in 2 industrialized regions of the 
Federal Republic of Germany.  In unwashed leaves collected from 38 
trees in Saarland in 1982, levels of between 0.002 and 0.2 mg Be/kg 
dry weight were found compared with 0.2 - 5 mg/kg dry weight in 
samples of upper soil layers.  The poplar leaves collected in the 
Ruhr area in 1979 contained beryllium levels of between 0.003 and 
0.03 mg/kg dry weight.  In samples of grass  (Lolium multiflorum), 
from the same environment as the poplar trees, concentrations of 
between 0.002 and 0.03 mg/kg were found.  The considerable local 
variations in the beryllium contents observed could not be related 
to any environmental factors. 

    The same working group analysed spruce needles in the Saarland 
(Federal Republic of Germany) in 1982 and 1984 (Mueller et al., 
1986).  One-year-old needles contained between 0.002 and 0.033 
mg/kg (mean:  0.013 mg/kg) and 2-year-old needles contained between 
0.004 and 0.065 mg/kg dry weight (mean:  0.022 mg/kg).  Animals

   Meehan & Smythe (1967) analysed various marine organisms and 
found beryllium levels ranging from non-detectable amounts in eels 
to 106 µg/kg fresh weight in Cunjevoi tunicates  (Pyura 
 stolonifera).  Byrne & DeLeon (1986) collected samples of oysters 
 (Crassostrea virginica) and clams  (Rangia cuneata) from Lake 
Pontchartrain, an estuary located in the deltaic plain of the 
Mississippi River.  Oysters contained an average of 51 µg Be/kg dry 
weight (5.1 µg/kg fresh weight), clams from one site contained 83 
µg/kg dry weight (12 µg/kg fresh weight), and those from another 
site contained 380 µg/kg dry weight (54 µg/kg fresh weight). 

    Beryllium concentrations in the blubber of bowhead whales 
 (Balaena mysticetus) from the western Arctic were below the limit 
of detection (10 µg/kg) in 6 samples and 10 µg/kg fresh weight in 
one sample.  Of the various tissues analysed, only the liver 
contained detectable amounts of beryllium (244 µg/kg fresh weight) 
(Byrne et al., 1985). 

    Investigating the suitability of bird feathers as 
bioaccumulation indicators of heavy metals, Mueller et al. (1984) 
measured between < 5 µg and 50 µg Be/kg dry weight in different 
feathers of 3 jays  (Garrulus glandarius), caught in Saarland, 
Federal Republic of Germany. 

5.2  General Population Exposure

    For the general population not exposed to extraordinary sources 
of beryllium, the principal sources of exposure seem to be food and 
drinking-water; inhaled air and ingested dust are of minor 

    The daily human intake of beryllium from food has not been 
determined, since the data on beryllium levels in food (section 
5.1.4) are insufficient for a reliable estimation.  In a study in 
the United Kingdom (Hamilton & Minsky, 1973), the average dietary 
intake was estimated to be < 15 µg/day.  US EPA (1987) calculated a 
total daily consumption of 422.8 ng, most of which came from food 
(120 ng/day) and drinking-water (300 ng/day), while air (1.6 
ng/day) and dust (1.2 ng/day) reportedly contributed very little to 
the total intake of beryllium. 

    Although, from a toxicological point of view, the pulmonary and 
dermal routes are the decisive routes, the dietary intake of 
beryllium could explain the "normal" body burden resulting in a 
urine level of beryllium of approximately 1 µg/litre (section 6.3). 

    Tobacco smoking is probably a major source of exposure in the 
general population.  Up to 0.074 µg Be/cigarette has been reported 
to be in the smoke (section 5.1.5), hence, assuming that the smoke 
is entirely inhaled, an average smoker (20 cigarettes per day) 
takes in approximately 1.5 µg Be/day. 

    In the vicinity of point sources (section 5.1.1), the beryllium 
intake through air and dust can be increased by 2 - 3 orders of 
magnitude.  In addition, possible secondary occupational or 
"para-occupational" exposure of workers' families may significantly 
increase the beryllium intake through dust, when the clothes of 
occupationally exposed persons are not kept at the work-place, as 
was usually the case in the 1940s.  Investigating several cases of 
non-occupational beryllium disease, Eisenbud et al. (1949) 
conducted air analyses during simulated home laundering of work 
clothes worn by employees at a beryllium-producing plant.  When the 
clothes were shaken, a short-term beryllium level of 125 - 2000 
µg/m3 (mean:  500 µg/m3) was measured in the indoor air.  During 
the whole laundering procedure, an estimated amount of 
approximately 17 µg/day could be inhaled by a person.  Such 
"neighbourhood cases", i.e., patients in which beryllium disease 
occurred as a result of indirect exposure outside a plant (NIOSH, 
1972), were first reported by Gelman (1938). 

    Of the various applications of beryllium, only two possible 
sources of exposure for the general population could be of 
significance, i.e., mantle-type camping lanterns and some dental 
alloys (section 3.2).  The mantle of a gas lantern contains about 
650 µg beryllium in the form of its oxide.  The experiments of 
Griggs (1973) revealed that most of the beryllium (about 400 µg) is 
volatilized in the first 15 min of burning a new, unused mantle.  
It was estimated that, in a 14 m3-camper vehicle, a relatively high 
short-term concentration of around 18 µg Be/m3 could occur in the 
first few minutes.  Since the beryllium emission is principally 
confined to the process of lighting a new mantle, long-term 
exposure to significant amounts would not be expected. 

    Because of a potentiated leakage effect, the dissolution of 
beryllium from dental alloys that contain nickel and beryllium was 
several orders of magnitude greater than expected (Covington et 
al., 1985b).  After incubation of pieces of dental alloys (squares 
1 cm2 x 0.1 cm) in 5 ml human saliva for 120 days at 37 °C, the 
saliva contained, depending on the alloy tested, between 0.3 and 
3.48 mg Be/litre at pH 6 and between 12.4 and 43.0 mg/litre at pH 
2.  It should be noted that the normal pH of saliva is between 5.8 
and 7.1. 

    Historically, the use of beryllia in fluorescent tube 
phosphors, and particularly the disposal of broken tubes, were 
important sources of exposure to beryllium and resulted in many 
cases of beryllium disease.  The production of beryllium-containing 
fluorescent tubes was discontinued in 1949, but it appears that 
they were still in use in Europe after that date (Tepper, 1972). 

    Emission and exposure standards for beryllium in ambient air in 
the neighbourhood of beryllium production and processing plants 
have been established in the USA and USSR.  In the USA, beryllium-
related industries are required to limit atmospheric emissions of 
beryllium to 10 g over a 24-h period or to an ambient air level of 

0.01 µg/m3, as a monthly average (US EPA, 1978a).  The maximum 
allowable concentration (MAC) for ambient air, established in the 
USSR, is 0.01 µg/m3 (Izmerov, 1985). 

    USA regulations also require that emissions of beryllium from 
rocket-motor firing must not exceed 75 µg/(min x m3) for low-fired 
(500 °C) beryllium oxide and 1500 µg/(min x m3) for high-fired 
(1500 °C) beryllium oxide, both measured within the time limit of 
10 - 60 min, accumulated during any 2 consecutive weeks, at the 
property line or nearest place of human habitation (Reeves, 1986). 

5.3  Occupational Exposure

5.3.1  Exposure levels

    The range of industrial processes with potential occupational 
exposure to beryllium has expanded during recent years.  Such 
industries include mining and processing activities, extraction 
plants, the manufacture of beryllium alloys, beryllium chemicals, 
and beryllium ceramics, non-ferrous foundries, the manufacture of 
electronic and aerospace equipment, tools, and dies, metallurgical 
operations, golf club manufacturing, and other processing of 
beryllium-containing metals and ceramics.  In these industries, 
beryllium is released during various processes, such as melting, 
casting, moulding, grinding, buffing, welding, cutting, 
electroplating, milling, drilling, and baking.  In addition, 
occupational exposure to the dust or fumes of beryllium may occur 
at rocket-motor test sites, incinerators, and open-burning sites 
(IARC, 1980; Newland, 1982; Kjellström & Kennedy, 1984; OSHA, 
Personal communication 1989).  In the USSR, beryllium may be 
released during the production of emeralds (Sidorenko, Personal 
communication, 1988). 

    In 1971, approximately 8000 plants were operating in the USA 
with about 30 000 employees potentially exposed to beryllium, 2500 
of whom were involved in the production industry (NIOSH, 1972).  
Health risks from beryllium exposure can still occur, particularly 
in the production industry, in which extraction and sintering 
processes are not easy to control (Preuss & Oster, 1980). 

    Before 1950, many cases of beryllium disease were caused by the 
high exposure of workers to beryllium metal and its compounds, 
during processing and manufacturing activities.  Although there is 
a lack of quantitative data on exposure to beryllium prior to 1947, 
there seems to be little doubt that extremely high concentrations 
were encountered in the work-place (NIOSH, 1972). 

    In the USA, concentrations greater than 1 mg beryllium/m3 were 
not unusual (Eisenbud & Lisson, 1983).  Laskin et al. (1950) 
reported dust concentrations of 110 - 533 µg Be/m3 during the coke 
removal operation and 1473 - 4710 µg/m3 during the beryllium-
pouring phase.  Exposure levels of up to 43 300 µg/m3 were reported 
by Zielinski (1961) for the breathing zone in an alloy plant. 

    High exposure to beryllium occurred during the production of 
fluorescent and neon lamps when beryllium was used, together with 
other metal salts, to coat the inner surface (Kjellström & Kennedy, 
1984).  After the discovery of an epidemic of beryllium disease 
among fluorescent lamp workers, this use of beryllium was 
discontinued in the USA in 1949. 

    In the USSR, similar exposure conditions were prevalent in the 
beryllium industry in its early years (Izmerov, 1985).  For 
instance, during the electrolysis of beryllium salts, atmospheric 
beryllium concentrations between 5 and 700 µg/m3 were reported. 

    In 1949, the US Atomic Energy Commission, one of the largest 
consumers of beryllium at that time, introduced permissible 
exposure concentrations of beryllium that were subsequently adopted 
by the American Conference of Governmental Industrial Hygienists 
(ACGIH) in 1955 (NIOSH, 1972). 

    In the 1950s, control measures were installed in beryllium 
plants to meet occupational standards.  As a result, exposure to 
beryllium was considerably reduced.  For example, in an Ohio 
extraction plant where control measures were applied, the exposure 
levels were 2 µg Be/m3 or less in 90 - 95% of about 2600 air 
samples analysed (Breslin & Harris, 1959). 

    However, the US permissible exposure limit of 2 µg/m3 was still 
being exceeded in various plants.  In the Ohio plant, 5 - 10% of 
the samples still contained concentrations greater than 25 µg/m3.  
In the early 1970s, peak concentrations in a beryllium extraction 
and processing plant were over 50 times the accepted peak limit 
value (25 µg/m3), i.e., up to 1310 µg/m3 (Kanarek et al., 1973).  
Follow-up analyses in 1974 showed a significant decrease in the 
exposure levels (Sprince et al., 1978).

     In a copper-beryllium alloy production plant, the 2 µg/m3 
limit was considerably exceeded during the monitoring period 
between 1953 and 1960, with time-weighted average values of 
4.4 - 9.5 µg/m3 in 1953, 9.2 - 19.1 in 1956, and 23.1 - 54.6 µg/m3 
in 1960 (NIOSH, 1972). 

    A wide range of worker exposure levels is frequently 
encountered.  In a beryllium-alloy plant, concentrations ranged 
from < 0.1 µg/m3 in the mixing areas to 1050 µg/m3 in the oxide 
areas (Cholak et al., 1967).  The 5-day average level in this plant 
was 60.3 µg/m3. 

    The US Atomic Energy Commission presented exposure data from 5 
major beryllium-processing plants, for various periods during 
1950 - 61 (NIOSH, 1972).  Up to 40 - 75% of the average breathing-
zone concentrations exceeded 2 µg/m3, depending on the 
effectiveness of the control measures installed.  Maximum recorded 
levels were as high as 550 µg/m3.  However, values exceeding 50 
µg/m3 were apparently due to the failure of control devices. 

    The National Institute of Occupational Safety and Health 
(NIOSH) conducted several air surveys in different beryllium 
facilities in the USA.  Personal air samples taken at factories 
where machining of beryllium metal and alloys involved drilling, 
boring, cutting, and sanding operations, did not reveal any 
detectable amounts of beryllium (Gilles, 1976; Boiano, 1980; Lewis, 
1980).  In a boat factory where workers were engaged in grid 
blasting operations, beryllium concentrations of between 6 and 134 
µg/m3 were measured.  This indicates potential overexposure, since 
respirators were not worn consistently (Moseley & Donohue, 1983).  
In a beryllium production plant, concentrations of between 0.3 and 
160 µg/m3 were found in a 1971 survey, the high values appearing in 
the powdering operations (Donaldson, 1971).  In another beryllium 
production plant, the concentrations of airborne beryllium, as 
measured in 1972 surveys, rarely exceeded the TLV of 2 µg/m3 
(Donaldson & Shuler, 1972).  Beryllium concentrations in 50 
personal samples collected at a secondary copper smelter in 1982 
ranged between < 0.2 and 0.5 µg/m3 (Cherniack & Kominsky, 1984).  
In 1983, 121 personal air samples were obtained in the refinery and 
manufacturing melt areas of a precious metals refinery.  The 
beryllium concentrations ranged from 0.22 to 42 µg/m3 (mean 1.4 
µg/m3) (McManus et al., 1986).  Concentrations in the beryllium 
shop of another plant ranged from <0.2 to 7.2 µg/m3, with a mean 
of 0.4 µg/m3 (Gunter & Thoburn, 1986). 

    Casting aluminium alloys with 4% beryllium was associated with 
beryllium air levels in the range of 0.006 - 0.14 µg/m3.  The most 
extensive emission of beryllium occurred during the refining of the 
alloy.  Changes in technology, the exclusion of the refining 
process, and the installation of ventilation reduced the beryllium 
concentrations to 0.001 - 0.004 µg/m3 (Naumova, 1967). 

    A 1983 report showed that compliance with permissible limits 
was not being consistently attained during the grinding, polishing, 
cutting, and welding of beryllium-containing alloys in a metal-
processing plant in the Federal Republic of Germany (Minkwitz et 
al., 1983).  Breathing-zone air sampling revealed concentrations of 
between 0.1 and 11.7 µg Be/m3 in the total dust (sampling duration: 
32 - 133.5 min; analytical method according to NIOSH, 1977).  The 
technical guidance concentrations (TRK) established in the Federal 
Republic of Germany were exceeded, particularly during the cutting 
of alloys using a hand cutter (0.1 - 10.0 µg/m3) or an automatic 
cutting machine (1.4 - 11.7 µg/m3) and during the welding process 
(2.1 - 3.63 µg/m3 without exhaust extraction; and 1.12 - 1.34 
µg/m3 with exhaust extraction). 

    Bobrischev-Pushkin et al. (1975) reported that air 
contamination, when welding beryllium and its alloys, is determined 
by the process of welding and depends on the technology and the 
concentration of beryllium in the materials being used.  The 
highest emissions of beryllium into the air occur during argon-arc 
welding.  During diffusion and electric-beam welding, air 
contamination occurs while taking the welded objects out of the 
welding chambers.  It is at its highest during the cleaning of the 
welded objects.  The concentration of beryllium in the air can 

differ greatly, according to its ratio with other metals in the 
welded alloys.  Flux-core welding promotes the liberation of water-
soluble beryllium salts and requires protective measures to prevent 
damage to mucous membranes and the skin. 

    The exposure of dental laboratory technicians to beryllium, 
during the processing of beryllium-containing dental alloys, has 
been investigated.  Analyses of air samples collected in the 
breathing zone showed that 2.0 µg/m3 was not exceeded when exhaust 
extraction was used (Dvivedi & Shen, 1983).  However, the use of an 
electric handpiece without exhaust extraction produced a beryllium 
concentration of 74.3 µg/m3, compared with a concentration of 1.75 
µg/m3 when exhaust extraction was used. 

    In the USA, a newly identified use for beryllium-copper alloy 
has been reported.  Workers grinding, polishing, and finishing golf 
club heads, made from this alloy, were exposed to average beryllium 
breathing zone concentrations ranging from 2 to 14 µg/m3 (OSHA, 
Personal communication, 1989). 

    To meet industrial hygiene standards, the installation, 
maintenance and, if necessary, improvement of control measures is 
required.  Engineering controls should provide safe work-place 
atmospheres, and should include closed systems and special local 
exhaust devices (Preuss, 1975).  Personal protective devices, such 
as respirators, should be used in cases where high atmospheric 
concentrations result during emergencies or maintenance or repair 
(NIOSH, 1972). 

5.3.2  Occupational exposure standards

    The first hygiene standards for beryllium were introduced by 
the US Atomic Energy Commission in 1949, on the basis of the 
recommendations of Eisenbud et al. (1948, 1949).  The short-term 
exposure limit of 25 µg/m3, suggested by these authors, was derived 
from limited investigations (section 9).  There was no real 
empirical basis for the establishment of the long-term occupational 
exposure level of 2 µg/m3, which was derived, not from animal and 
human data, but by analogy with industrial air limits for the 
toxicity of other heavy metals (NIOSH, 1972).  The values of 2 
µg/m3, as an 8-h time-weighted average (TWA), 5 µg/m3, as a 30-min 
ceiling limit, and 25 µg/m3, as an instantaneous maximum peak 
exposure limit, never to be exceeded, were adopted in 1971 as the 
permissible exposure limits in the USA.  In addition, beryllium and 
its compounds are grouped within the group of A2 carcinogens, i.e., 
industrial substances suspected to have carcinogenic potential for 
man (ACGIH, 1988). 

    In the USSR, the occupational exposure limit is 1 µg/m3.  In 
addition, maximum allowable levels (MAL) of 2 mg/m2 for smooth and 
low-sorbing materials, 5 mg/m2 for readily sorbing materials, and 
0.5 mg/m2 for the floors of offices and public rooms, have been 
established (Izmerov, 1985). 

    Several countries have adopted the exposure limits of either 
the USA or the USSR (WHO,1990).  In the Federal Republic of 
Germany, the formerly legally binding MAK value (maximum 
concentration value in the work-place) of 2 µg Be/m3 was redefined 
as a technical guiding concentration (TRK) in 1982, because of the 
carcinogenic potential of beryllium (DFG, 1988).  TRK values are 
assigned for carcinogenic substances to reduce the risk of a health 
hazard.  A TRK value of 5 µg/m3 (calculated as Be in total dust) 
has been established for grinding beryllium metal and alloys, 
apparently to meet the technical performance of the associated 
control measures.  For all other beryllium-related work processes, 
the TRK value is 2 µg/m3. 

    A downward revision of the US standard from 2 µg/m3 to 1 µg/m3 
(TLV) with a 15-min ceiling limit of 5 µg/m3, as well as a dermal 
exposure limit, were proposed by the Occupational Safety and Health 
Administration (OSHA, 1975).  The proposal also included medical 
surveillance and other auxiliary provisions, including periodic 
exposure monitoring, worker training and education, and labelling 
requirements.  As of 1989, the proposed standard had not been 

    The National Institute for Occupational Safety and Health 
(NIOSH) recommended "that occupational exposure to beryllium be 
controlled so that no workers will be exposed in excess of 0.5 
µg Be/m3" (NIOSH, 1977).  As NIOSH classifies beryllium as a 
carcinogen, control of beryllium exposure to maintain the lowest 
feasible limit is recommended.

    On the basis of animal carcinogenicity studies, it has been 
suggested in the USSR that the exposure limit in the air of working 
areas should be 0.01 µg/m3 (Parfenov, 1988). 

5.3.3  Biological monitoring

    Analysis of tissues and body fluids for beryllium can indicate 
previous exposure to beryllium.  However, because earlier 
analytical methods had relatively low sensitivities and were mostly 
not validated by proper quality control procedures, there is a lack 
of reliable data that could be used to establish the body burden of 
beryllium in occupationally exposed people, compared with that in 
the general population.  The "normal" level in urine is elevated 
following specific exposure, but this is not consistent (section 

    Attempts have been made to use the beryllium contents of the 
lung or lymph-node specimens as indicators of exposure and body 
burden.  Beryllium storage in tissues is of long duration, 
especially in pulmonary lymph nodes and bones (section 6.4).  As 
with urinary beryllium, it is not possible, using the limited data 
available, to establish a clear relationship between exposure and 
body burden, though clearly elevated levels are found in tissue 
samples of patients with beryllium disease (section 6.2). 

    Beryllium levels in lung tissue and urine may be of relevance 
from the medical point of view, because the detection of elevated 
beryllium levels in patients with lung disease is indicative of a 
beryllium-related disease.  On the other hand, low levels are not 
evidence for the absence of chronic beryllium disease.  Long-term, 
low-level exposure and the concomitant elimination of beryllium may 
result in a relatively low body burden.  Moreover, because of the 
allergic features of some of the effects of beryllium (section 9), 
it is possible that very low exposures can possibly cause signs and 
symptoms in previously sensitized persons. 

6.1  Absorption

6.1.1   Respiratory absorption

    Inhalation is the primary route of uptake of occupationally 
exposed persons.  There are no data on the deposition or absorption 
of inhaled beryllium in human beings, but it can be expected that, 
as with other inhaled particles, dose, size, and solubility are the 
important factors governing deposition and lung clearance. 

    Animal studies have shown that, after deposition in the lungs, 
beryllium is retained and slowly absorbed into the blood.  
Pulmonary clearance of inhaled beryllium is biphasic, with a fast 
elimination phase during the first 1 - 2 weeks after cessation of 
exposure and a slow elimination phase thereafter.  The initial fate 
of beryllium, deposited in the lung by inhalation or by 
intratracheal injection, depends on the physical and chemical 
states of the compounds present. 

    Van Cleave & Kaylor (1955) studied the kinetics of 7Be in the 
rat after intratracheal injection of trace amounts of either 7Be 
citrate or 7BeSO4.  Absorption of the soluble 7Be citrate complex 
from the alveoli into the blood was fast, as can be seen from the 
observation that almost 79% of the total injected dose had been 
eliminated in the urine and faeces by day 4 and only 2.5% remained 
in the lungs, decreasing to 1% at the end of 16 days.  The liver 
and skeleton were the sites of deposition of the mobilized 7Be.  On 
average, 55% of the original dose of the 7Be citrate was eliminated 
via the kidneys in the first 24 h, but only 15% of the 7BeSO4 dose 
was eliminated in the urine in that time, indicating a much slower 
absorption from the lungs into the blood.  At 16 days, 62% of the 
total dose had been eliminated in the urine and faeces; 70% of the 
remaining dose was still present in the lung.  Thereafter, 
pulmonary retention of beryllium decreased with a concomitant 
increased deposition in mediastinal lymphatic structures.  However, 
in some preparations of 7BeSO4, retention of appreciable amounts 
was still found after 315 days.  This finding probably resulted from 
the different particulate or colloidal features of the 7Be 

    Reeves et al. (1967) and Reeves & Vorwald (1967) also observed 
long retention of beryllium in the lungs of rats following exposure 
to a BeSO4 aerosol, at a mean concentration of 34 µg Be/m3, for 72 
weeks (7 h/day, 5 days/week).  An equilibrium concentration was 
reached in the lungs and tracheobronchial lymph nodes at about 36 
weeks.  After cessation of exposure, pulmonary beryllium was first 
eliminated with a half-time of about 2 weeks, followed by a 
logarithmically decreasing clearance rate.  However, some beryllium 
(0.2 - 0.7 µg/kg), remained in the lungs for years, probably in an 
encapsulated form. 

    In rats and guinea-pigs, Zorn et al. (1977) observed rapid lung 
clearance during the first 5 days following a 3-h nasal exposure to 

BeSO4 tagged with 7BeCl2.  Only 2% of the dose of approximately 
1634 µg Be per animal remained in the lungs after 5 days.  During 
the following 12 weeks, the pulmonary beryllium content further 
decreased to 1.5% of the whole body activity, confirming the very 
slow second elimination phase observed by Reeves & Vorwald (1967). 

    The relevance of the test material with respect to the 
clearance of beryllium from the lungs of rats can also be 
demonstrated by the results of several other studies.  Kuznetzsov 
et al. (1974) found a pulmonary half-time of 20 days following 
intratracheal administration of 7BeCl2 (10 µCi).  Bugryshev et al. 
(1976) found that 20% of an intratracheal dose of BeCl2 was 
retained in the lungs of rats, after 94 days.  Significant 
pulmonary retention of low-solubility BeO (unknown specification), 
which lasted for several months, with a retention half-life of 
approximately 12 months, was found in rats by Dutra et al. (1951).  
Sanders et al. (1975) and Rhoads & Sanders (1985) found alveolar 
half-times in rodents of about 6 and 13 months, respectively, after 
inhalation of high-fired (1000 °C ) BeO. 

    Most beryllium that is inhaled is in the form of particulate 
matter and must be mobilized by other means than passing directly 
into the blood.  This is mainly accomplished through the 
mucociliary transport of particles deposited in the 
tracheobronchial tree, (which, according to Camner et al. (1977), 
is probably responsible for the rapid clearance of inhaled 
particles during the first day), and also through the uptake of 
beryllium by alveolar macrophages.  Hart & Pittman (1980) observed 
that insoluble beryllium complexes were more effectively 
incorporated  in vitro than soluble compounds.  The temperature and 
energy dependency that was observed, together with the demand for 
calcium and magnesium ions, suggests that phagocytosis was 

    The results of studies by Lundborg et al. (1984) and Nilsen et 
al. (1988) showed that alveolar macrophages dissolved inorganic 
particles, probably because of the low pH in the phagolysosomes.  
André et al. (1987) found that the dissolution by alveolar 
macrophages of two industrial forms of beryllium, i.e., particles 
of metal powder and particles of hot-pressed beryllium, was 
consistent with the  in vivo clearance observed in rats and baboons. 

    Beryllium-coated particles were highly toxic to macrophages 
(Camner et al., 1974), indicating that elevated beryllium 
concentrations inhibit pulmonary clearance.  The decrease in the 
alveolar clearance of a test aerosol (239PuO2) to 60% of the normal 
rate, after exposure of rats to an aerosol of BeO was probably due 
to the inhibition of macrophages by incorporated beryllium (Sanders 
et al., 1975). 

    Lung clearance of beryllium appears to be species and sex-
dependent.  Clearance was more rapid in hamsters than in rats, and, 
in both species, it was greater in males than in females (Sanders 
et al., 1975).  Reeves & Vorwald (1967) also observed a greater 
clearance rate in male rats than in females. 

6.1.2  Dermal absorption

    Uptake of beryllium through skin absorption contributes only 
very small amounts to the total body burden of beryllium-exposed 
persons.  However, because of the skin effects elicited by 
beryllium compounds, this route is of some significance. 

    Trace levels of 7BeCl2 were found to be absorbed at a low rate 
through the rat tail (Petzow & Zorn, 1974).  Although subsequent 
systemic distribution of trace amounts of beryllium was observed, 
systemic distribution through the intact skin is not expected 
following local contact, because most beryllium salts do not remain 
soluble at physiological pH (Reeves, 1986).  Belman (1969) studied 
the beryllium-binding properties of epidermal constituents of 
guinea-pigs and found that ionic beryllium applied to the skin 
became bound mainly to alkaline phosphatase and nucleic acids. 

6.1.3  Gastrointestinal absorption

    Faecal elimination of beryllium following its uptake through 
inhalation (section 6.1.1) indicates that part of the inhaled 
material goes to the gastrointestinal tract, either by mucociliary 
action or by the swallowing of the insoluble material deposited in 
the upper respiratory tract (Kjellström & Kennedy, 1984). 

    Estimates from animal studies, in which trace amounts of 
carrier-free 7Be were administered as the chloride, show that 
absorption of ingested beryllium is very low, with values generally 
below 1% in pigs (Hyslop et al., 1943), rats, mice, monkeys, dogs 
(Crowley et al., 1949; Furchner et al., 1973) and cows (Mullen et 
al., 1972). 

    From the data reported by Reeves (1965), it appears that, in 
rats, the absorption rate for BeSO4 is much higher, since about 80% 
of the ingested beryllium (doses: 0.6 and 6.6 µg Be/day in the 
drinking-water) was eliminated with the faeces.  It was assumed 
that the remainder was absorbed from the stomach, at the pH of 
which the BeSO4 is in the ionized form; at the alkaline pH of the 
intestine, beryllium precipitates as the phosphate.  However, in 
contrast to other studies, Reeves (1965) did not use radionuclide 
7Be as tracer, but analysed beryllium by a spectrometric method.  
The recovery was only between 60 and 91% of the total consumption.  
On subtracting the measured beryllium content of the 
gastrointestinal tract from the total body burden plus the urinary 
beryllium, it is evident that only 0.06 - 1.5% of the total intake 
must have been absorbed from the gastrointestinal tract into the 
blood and distributed to the tissues or excreted by the kidneys. 

6.2  Distribution and retention

    Most of the beryllium circulating in the blood is transported 
as colloidal phosphate, and only small amounts are transported as 
citrate or hydroxide (Reeves, 1986).  Stiefel et al. (1980b) found 
that beryllium is bound to the prealbumins and gamma-globulin.  The 
relative distribution in these two fractions depends on the 

concentration of beryllium in the blood.  At 1 µg/kg, 8% is stored 
in the prealbumin and about 60% in the gamma-globulin.  Above 10 
µg/kg, the distribution is reversed. 

    There is also a binding site for beryllium on the lymphocyte 
membrane (Skilleter & Price, 1984). 

    Regardless of the animal species, a significant part of the 
beryllium administered is incorporated in the skeleton.  The extent 
to which beryllium is deposited in other target tissues depends on 
the route of administration, and the physical and chemical state, 
and dose of the compound. 

    Following oral administration of carrier-free 7BeCl2 (0.7 - 
1.3 mCi) to calves, only about 0.3% of the dose was absorbed from 
the gastrointestinal tract, of which approximately 90% wase found 
in the bone.  The remainder was mainly localized in the 
gastrointestinal tract and only 2% of the total body burden was 
found in the liver (Mullen et al., 1972). 

    In rats receiving an average daily dose of 6.6 µg Be per rat 
(BeSO4 in the drinking-water) for 24 weeks, 76% of the total body 
recovery, minus the beryllium content in the gastrointestinal 
tract, was in the skeleton, 16% in the blood, and 7% in the liver.  
At a dose of 66 µg/day, 85% of the beryllium retained was deposited 
in the skeleton, smaller amounts being found in the blood (11%) and 
the liver (3%) (Reeves, 1965).  The doses administered in this 
study were a factor of 1000 higher than those in the preceding 

    Scott et al. (1950) observed that carrier-free 7Be, injected 
intravenously in rats and rabbits, was mainly deposited in the 

    Less than 10% of an intravenous dose of BeSO4 (0.75 - 15 µg 
7Be/kg body weight) was found in the liver of rats, 24 h after 
administration, but more than 25% was found at doses of 63 µg/kg 
body weight or more (Witschi & Aldridge, 1968). 

    The distribution of intratracheally injected BeO is highly 
dependent on the properties of the compound used (Spencer et al., 
1965).  Relatively high levels of beryllium were found in the 
liver, kidney, and bone of rats that had been treated with low-
fired BeO (produced by calcining alpha-Be(OH)2 for 10 h at 500 °C).  
In contrast, beryllium from particles of high-fired BeO (1600 °C), 
which has a low solubility, remained mainly in the lungs and very 
little was distributed to the liver, kidneys, and bone.  However, 
no values were given by Spencer et al. (1965).  Rhoads & Sanders 
(1985) did not detect beryllium at any extrapulmonary site in rats 
following nose-only inhalation of BeO dust (1000 °C).  Clearance to 
the pulmonary lymph nodes was about 2%, 63 days after exposure. 

    In general, inhalation exposure to beryllium compounds results 
in long-term storage of appreciable amounts of beryllium in lung 

tissue, particularly in pulmonary lymph nodes (section 6.1.1), and 
in the skeleton, which is the ultimate site of beryllium storage.  
More soluble beryllium compounds are also translocated to the 
liver, abdominal lymph nodes, spleen, heart, muscle, skin, and 

    Bencko et al. (1979a) reported that the placental permeability 
for soluble 7BeCl2 (0.1 mg/kg body weight), intravenously 
administered to mice, was slight.  The concentrations of beryllium 
in the placenta and in the remaining organs of the females was one 
order of magnitude higher than those in the fetuses.  The transfer 
of ingested radioactive beryllium (3.1 mCi of carrier-free 7BeCl2 
per animal) to the milk was low (Mullen et al., 1972).  Less than 
0.002% of the administered activity was secreted in the milk of cows. 

    Apart from bone, the lung is considered to be the primary 
target organ in man.  Sprince et al. (1976) analysed specimens 
taken at autopsy and found less than 20 µg Be/kg dry weight in lung 
tissue (mean: 5 µg/kg; range: 3 - 10 µg/kg; 6 cases) and 
mediastinal lymph nodes (mean: 11 µg/kg; range: 6 - 19 µg/kg; 7 
cases) of control patients without granulomatous disease.  These 
levels are in agreement with the normal range of 2 - 30 µg Be/kg 
dry lung tissue covering 90% of the values found in 125 lung 
specimens obtained during thoracic surgery (Baumgardt et al., 1986). 

    Using inductively coupled plasma atomic emission spectrometry, 
Caroli et al. (1988) analysed different parts of lung tissue of 12 
subjects in the urban Rome area.  All were non-smokers, 50 or more 
years old, and had not been occupationally exposed to beryllium 
during their life-time.  The overall mean of 5 µg/kg fresh weight 
(median 6 µg/kg; 9th percentile 8 µg/kg) indicates a far smaller 
concentration range than those above, which were on a dry weight 

    Analysis of lung tissue from 66 patients with beryllium disease 
showed that 82% had Be levels of more than 20 µg/kg dry weight.  
Even higher levels were found in lymph-node specimens from 5 
patients; the peripheral lymph nodes contained between 2 and 490 µg 
Be/kg dry weight (mean: 110 µg/kg), the mediastinal nodes contained 
between 56 and 8500 µg/kg (mean: 3410 µg/kg) (Sprince et al., 1976). 

    From the examination of cases from the US Beryllium Case 
Registry (Freiman & Hardy, 1970), it appears that the levels of 
beryllium in the lungs of patients dying with acute disease are 
generally higher than those in patients with chronic disease.  As 
expected, neither lung nor urinary beryllium levels are correlated 
with the occurrence or severity of chronic beryllium disease 
(Tepper, 1972).  Apart from considerable variations in the 
beryllium concentrations of several samples from the same lung, 
great variability also exists in the tissue levels of beryllium in 
the patients.  There are more people with high beryllium body 
burdens and no beryllium disease than there are people with chronic 
beryllium disease.  For example, healthy refinery workers had 1000 
times higher values than persons with beryllium disease (Tepper, 

6.3  Elimination and excretion

    As pointed out in section 6.1, elimination of absorbed 
beryllium occurs mainly in the urine and only to a minor degree in 
the faeces.  Most of the beryllium taken up by the oral route 
passes through the gastrointestinal tract unabsorbed and is 
eliminated in the faeces. 

    Rats injected intramuscularly with carrier-free 7Be 
(approximately 20 mCi, i.e., 57 ng 7Be per rat) eliminated 15%, 
14.6%, 24.4%, and 44% of the dose in the urine at 1, 4, 16, and 64 
days, respectively, versus 4.25%, 4.17%, 9.25%, and 13.1% in the 
faeces (Crowley et al., 1949). 

    After intravenous administration of very small doses of 
carrier-free 7Be to rats (0.09 ng Be/kg body weight) and rabbits 
(0.04 ng Be/kg body weight), urinary excretion was the major 
elimination route (Scott et al., 1950).  Elimination was greatest 
during the first 24 h and amounted to 38.8% of the total dose in 
rats and 28.8% in rabbits.  In comparison, animals receiving 7Be 
plus BeSO4 as a carrier, and, thus, a relatively large dose of 0.15 
µg Be/kg body weight (rats) or 0.05 µg/kg body weight (rabbits), 
excreted only 24.2% (rats) or 14% (rabbits) of the dose in the 
urine.  This reduction of the urinary excretion rate with 
increasing dose may be explained by the increasing immobilization 
of beryllium, because of its binding on proteins.  Faecal 
elimination of beryllium was comparatively low during the first 
day, with only 0.1% of the dose excreted by this route in rabbits 
and 3.5% (carrier-free 7Be) or 4.2% (with carrier) in rats.  
Following the first rapid urinary elimination phase, the daily 
urinary elimination in rabbits varied between 0.5 and 1.8% of the 
dose with a concomitant faecal elimination of 0.2 - 0.5%. 

    This observation is consistent with the results of Furchner et 
al. (1973) who determined urinary/faecal ratios of 3.21 in mice and 
10.2 in rats, during the first 24 h after intraperitoneal 
administration, and 3.5 in mice, 21.34 in rats, 4.03 in monkeys, 
and 48.61 in dogs after intravenous administration.  Thereafter, 
the high urinary excretion rate declined rapidly and the amount 
lost in the faeces equalled that in the urine.  The mechanism of 
urinary excretion is probably active tubular secretion, because 
most of the colloidally bound plasma beryllium does not pass the 
glomerulus in the kidney (Reeves, 1986). 

    True biliary excretion seems to play a minor role in total 
beryllium elimination (Cikrt & Bencko, 1975).  Elevated amounts of 
beryllium eliminated in the faeces after intratracheal or 
inhalation administration are probably the result of clearance from 
the respiratory tract and ingestion of swallowed beryllium. 

    Quantitative data on the excretion of beryllium in human beings 
are confined to some urinary levels in exposed and non-exposed 

    Twenty of 22 non-occupationally exposed persons living in the 
vicinity of beryllium plants did not have any beryllium (< 0.02 
µg/litre) in their urine, though 8 of them were suspected of, or 
diagnosed as, having berylliosis.  Two persons living near a 
beryllium refinery (0.4 km distance) showed urine concentrations of 
0.02 and 0.06 µg Be/litre, respectively (Lieben et al., 1966).  
Grewal & Kearns (1977) found an average concentration of 0.9 ± 0.4 
µg/litre in 120 people from California.  A similar value (0.9 ± 0.5 
µg/litre) was reported by Stiefel et al. (1980a) for 20 non-
occupationally exposed persons from the Federal Republic of 
Germany.  It appears that a "normal" beryllium level in urine is 
around 1 µg/litre.  However, this level seems much too high 
considering that gastrointestinal absorption of beryllium into the 
blood is very low.  From the estimated inhalation intake of 1.6 ng 
Be/day per person it can be assumed that only a few nanograms of 
beryllium will be excreted daily (US EPA, 1987). 

    The discrepancy between the reported and expected urinary 
beryllium levels cannot be explained.  The contribution of food is 
unclear, since reliable data are not available (section 5.1.4).  
Human data on the bioavailability of ingested beryllium are also 
lacking.  Moreover, the studies have not distinguished between 
smokers and non-smokers.  Stiefel et al.(1980a) reported levels of 
about 2 µg Be/litre in the urine of smokers. 

    An increase in urinary beryllium of several µg/litre, following 
inhalation exposure to beryllium, was reported by Hardy & 
Chamberlin (1972).  In the urine of 8 laboratory assistants, the 
beryllium concentration increased from 1 µg/litre to about 4 µg/
litre, when the beryllium concentration in the laboratory air 
increased from about 0.4 ng/m3 to 8 ng/m3, because of accidental 
contamination with BeCl2 (Stiefel et al., 1980a).  However, Lieben 
et al. (1966) only found levels ranging between non-detectable 
(< 0.02 µg/litre) and 0.26 µg/litre in the urine of beryllium 

6.4  Biological half-life

    A distinction must be made between the elimination of inhaled 
beryllium from the lungs, and the total elimination of beryllium 
from the body.  In the first case, studies indicate that only the 
non-ionized soluble forms of beryllium, such as the citrate, are 
cleared from the lung rapidly (in about 4 days).  The ionized 
soluble forms become precipitated in lung tissue and behave like 
particulate matter.  Their clearance consists of a "fast phase" and 
a "slow phase".  The fast phase is probably because of uptake in 
macrophages, which subsequently migrate out of the bronchopulmonary 
system (Van Cleave & Kaylor, 1955; Kuznetsov et al., 1974; Hart & 
Pittman, 1980; Hart et al., 1984; Finch et al., 1986).  The half-
time of the fast phase is in the range of 1 - 60 days (Sanders et 
al., 1975; Rhoads & Sanders, 1985).  The slow phase of beryllium 
clearance has a half-time of 0.6 - 2.3 years and it may represent 
the slow dissolution and dissipation of the deposits that have 
either become encapsulated in scar tissue or otherwise rendered 

unavailable to the phagocytic action of migratory cells (Reeves, 
1968; Rhoads & Sanders, 1985; Finch et al., 1986).  There appears 
to be a sex difference in the efficiency of clearance, at least in 
rats, favouring males compared with females (Reeves & Vorwald, 
1967; Reeves, 1968). 

    After intravenous injection of carrier-free 7BeCl2, Furchner et 
al. (1973) calculated biological half-lives of 1210, 890, 1770, and 
1270 days in mice, rats, monkeys, and dogs, respectively. 

    In human beings, the residence time for beryllium in the lung 
may be several years, since appreciable amounts of beryllium can be 
found in people, many years after cessation of exposure to 
beryllium (section 5.3.3).  In a report of the International 
Commission on Radiological Protection (ICRP, 1960), the biological 
half-life of beryllium in human beings was calculated to be 180, 
120, 270, 540, and 450 days in the total body, kidneys, liver, 
spleen, and bone, respectively. 


7.1  Microorganisms

    Little is known about the effects of beryllium on 
microorganisms.  In an earlier study, Pirschle (1935) noted a 
marked stimulating effect of higher concentrations of BeCl2 (0.1 - 
0.001 mol/litre) and BeSO4 (0.1 - 0.01 mol/litre) on mycelial 
growth.  Be(NO3)2 did not affect growth, but suppressed the 
formation of conidia.  The effects of beryllium were more 
comparable with those of aluminium than with those of the other 
alkaline earths, reflecting its specific chemical properties 
(section 2.2). 

    Gormley & London (1973) performed various experiments using 
mixed and pure soil microorganisms grown in media containing 100 
mg/litre of BeSO4 x 4H2O complexed with sodium citrate.  They did 
not observe any inhibitory effects of beryllium on cell growth.  In  
one  mixed  culture,  a  20-h delay  before  the  onset  of  the  
log phase  of  growth  occurred.  However,  in  this  culture,  a  
higher yield of biomass was noted compared with the control.  Soil 
micro-organisms, grown in a magnesium-deficient medium, grew better 
in the presence of beryllium, indicating that beryllium can 
substitute magnesium to some extent.  This effect has also been 
observed in plants (section 7.3) and could be responsible for the 
stimulatory effects reported. 

    Studies on  Pseudomonas aeruginosa showed that several growth 
factors are affected by potassium dioxalatoberyllate (K2[Be(C2O4)2]) 
at concentrations of 8 µmol/litre (72 µg/litre) or more.  Also the 
production of the pigment pyocyanin was found to be inhibited 
(MacCordick et al., 1976). 

    Bringmann & Kuehn (1981) determined the growth-inhibiting 
effects of beryllium nitrate, Be(NO3)2 x 4H2O, in protozoa. 
The toxicity threshold levels were 0.004 mg Be2+/litre for   the
flagellate  Entosiphon sulcatum Stein, 0.017 mg/litre for the 
ciliate  Uronema parduczi Chatton-Lwoff, and 0.51 mg/litre for the 
flagellate  Chilomonas paramaecium Ehrenberg. 

    Wilke (1987) investigated the effects on soil microorganisms of 
BeSO4 added to fertilizers.  At a concentration of 30 mg Be/kg 
soil, the biomass was reduced to 60% and nitrogen-mineralization to 
57% of the control.  At 80 mg/kg, the activities of dehydrogenase, 
saccharase, and protease were also inhibited, while ATP-content, 
alkaline phosphatase activity, and nitrification were unaffected. 

7.2  Aquatic organisms

7.2.1  Plants

    Hoagland (1952a) found that BeSO4 x 4H2O, at concentrations of 
2 x 10-4 to 3 x 10-4 mol Be/litre (1.8 - 2.7 mg/litre), inhibited 
growth of the green alga  Chlorella pyrenoidosa by only 5.6 ± 5.9% 

at an initial pH of 11.4, which decreased to about pH 7 in 24 h.  
In further experiments, Hoagland (1952a) observed that, at a low 
initial pH of 6.3, growth of both magnesium-deficient (1 x 10-4 mol 
Mg/litre) and high-magnesium algae (2 x 10-3 mol Mg/litre) was 
depressed by the addition of beryllium (2 x 10-4 mol Be/litre).  
However, at pH 11.4, beryllium had a stimulatory effect, probably 
because it became available to the algae and substituted magnesium 
in the growth process, but not in the demands of chlorophyll. 

    Karlander & Krauss (1972) showed that the growth of  Chlorella 
 vannieli was inhibited by BeCl2 at a concentration of 100 mg 

7.2.2  Animals

    Laboratory studies on the acute toxicity of beryllium for 
freshwater species are summarized in Table 9.  Only one 
invertebrate species  (Daphnia magna) has been studied.  Some 48-h 
EC50 values were 7.9 mg Be/litre for BeCl2 and 18.0 mg Be/litre for 
Be(NO3)2.  In fish species, LC50 values varied from 0.15 to 32.0 mg 
Be/litre, depending on the species and test conditions. 

    Beryllium sulfate was one to two orders of magnitude more toxic 
for fathead minnows and bluegills in soft water than in hard water 
(Tarzwell & Henderson, 1960).  Slonim & Slonim (1973) noted an 
exponential increase in the toxicity of beryllium for guppies, with 
decreasing hardness. 

    Salamander larvae showed a similar sensitivity to beryllium 
(Table 9) and were also more adversely affected in soft than in 
hard water (Slonim & Ray, 1975). 

     The effects of beryllium on the development of early-life 
stages have been examined in few studies.  Dilling & Healey (1926) 
examined the germination of frog spawn and the growth of tadpoles.  
Beryllium nitrate at concentrations of 0.9 - 4.5 mg Be/litre did 
not interfere with the development of eggs of undefined frog 
species and tadpoles grew well at concentrations of 0.09 - 0.2 mg  
Be/litre.  Hildebrand & Cushman (1978) did not observe any adverse 
effects on the development of eggs of the carp  (Cyprinus carpio) at 
beryllium concentrations below 0.08 mg/litre.  However, 
concentrations above 0.2 mg/litre reduced hatching success to 0%.  
The hardness of the spring water used was approximately 50 mg 
CaCO3/litre and carp eggs responded only slightly more sensitively 
than adult fish under these low hardness conditions. 

    US EPA (1980) cited a comparative toxicity study on  Daphnia 
 magna.  The 48-h EC50 and chronic toxicity values in the same test 
water (hardness: 220 mg CaCO3/litre) were 2500 and 5.3 µg Be/litre, 
respectively, indicating a large difference between acute and 
chronic toxicity.  No effects on reproduction were observed at 3.8 

Table 9.  Acute toxicity of beryllium for freshwater animals
Test species           Test     Test         Hardness   Test      Effect   Concentration  Reference
                       type     chemical     (mg/litre  duration           (mg Be/litre)
                                             as CaCO3)  (h)       
Water flea             static   beryllium    300        24        LC50     18             Bringmann &
 (Daphnia magna)                 nitrate                                                   Kühn (1977)

Water flea             static   beryllium    180        48        EC50     7.9            US EPA 
 (Daphnia magna)                 chloride                                                  (1978b)

Bluegill  (Lepomis      static   beryllium    20         96        LC50     1.3            Tarzwell &
 macrochirus)                    sulfate                                                   Henderson 

Bluegill  (Lepomis      static   beryllium    400        96        LC50     12             Tarzwell &
 macrochirus)                    sulfate                                                   Henderson 

Brook trout            static   beryllium    140        96        LC50     5              Cardwell et 
 (Salvelinus fontinalis)         sulfate                                                   al. (1976)

Channel catfish        static   beryllium    140        96        LC50     5              Cardwell et 
 (Ictalurus punctatus)           sulfate                                                   al. (1976)

Fathead minnow         flow-    beryllium    140        96        LC50     3.25           Cardwell et 
 (Pimephales promelas)  through  sulfate                                                   al. (1976)

Fathead minnow         static   beryllium    20         96        LC50     0.15-0.2       Tarzwell &
 (Pimephales promelas)           sulfate                                                   Henderson 

Fathead minnow         static   beryllium    400        96        LC50     11-20          Tarzwell &
 (Pimephales promelas)           sulfate                                                   Henderson 

Flagfish               flow-    beryllium    140        96        LC50     3.5-4.4        Cardwell et 
 (Jordanella floridae)  through  sulfate                                                   al. (1976)

Goldfish               flow-    beryllium    147        96        LC50     4.8            Cardwell et 
 (Carassius auratus)    through  sulfate                                                   al. (1976)

Table 9 (contd.)
Test species           Test     Test         Hardness   Test      Effect   Concentration  Reference
                       type     chemical     (mg/litre  duration           (mg Be/litre)
                                             as CaCO3)  (h)       
Guppy  (Poecilla        static   beryllium    22         96        LC50     0.16           Slonim & 
 reticulata)                     sulfate                                                   Slonim  

Guppy  (Poecilla        static   beryllium    150        96        LC50     6.1            Slonim & 
 reticulata)                     sulfate                                                   Slonim  

Guppy  (Poecilla        static   beryllium    275        96        LC50     13.7           Slonim & 
 reticulata)                     sulfate                                                   Slonim

Guppy  (Poecilla        static   beryllium    400        96        LC50     20             Slonim & 
 reticulata)                     sulfate                                                   Slonim  

Guppy  (Poecilla        static   beryllium    450        96        LC50     19-32          Slonim & 
 reticulata)                     sulfate                                                   Slonim  

Salamander larvae      static   beryllium    22         96        LC50     3.2-8.3        Slonim & 
 (Ambystoma maculatum)           sulfate                                                   Ray (1975)

Salamander larvae      static   beryllium    400        96        LC50     18-31          Slonim & 
 (Ambystoma maculatum)           sulfate                                                   Ray (1975)
7.3  Terrestrial organisms

7.3.1  Plants

    In studies with controlled nutrient media, Hoagland (1952a) 
demonstrated a definite relationship between the presence of the 
chemically similar magnesium and the effects of beryllium on the 
growth of tomato plants.  At a pH above 9, addition of 2 x 10-4 mol 
Be/litre (1.8 mg/litre) as BeSO4 x 4H2O to magnesium-deficient 
solutions produced rapid growth without evidence of magnesium 
deficiency; in the absence of beryllium, growth was depressed and 
chlorosis occurred within 2 weeks.  It seems that beryllium can 
reduce the magnesium requirement of plants, but not absolutely, as 
plants with higher levels of magnesium deficiency grew at a slower 
rate and died with no sign of chlorosis.  The pH-dependency of 
these phenomena raises the question as to whether the beryllate ion 
(BeO2--), formed above a pH of 8, is the biologically active agent. 

    At more acidic pH values and at higher bioavailable 
concentrations, beryllium is phytotoxic.  Romney et al. (1962) 
noted a definite decrease in the total dry weights of bush beans 
 (Phaseolus vulgaris) grown in nutrient solutions at a controlled pH 
of 5.3.  The mean total dry weights were 60.2, 40.2, 35.5, 20.6, 
14.5, and 7.3 g from the 0, 0.5, 1, 2, 3, and 5 mg Be/litre 
cultures, respectively.  Reduction of yield was also seen in soil 
cultures of beans, wheat, and ladino clover at beryllium levels  
corresponding to 4% of the cation-exchange capacity in soil (Romney 
& Childress, 1965).  Effects were first observed on the roots, 
which turned brown and failed to resume normal elongation.  It 
should be noted that roots accumulated most of the beryllium taken 
up, and very little was translocated to the upper parts of  the 
plants.   Stunting of both roots and foliage occurred, but there 
was no chlorosis or mottling of foliage. 

    Williams & Le Riche (1968) observed similar effects and reduced 
yield in kale grown in a nutrient culture solution containing more 
than 2 mg/litre of beryllium (as BeSO4 x 4H2O). However, at a 
concentration of 0.5 mg/litre, the yield was greater than in the 

    Hara et al. (1977) grew cabbage plants  (Brassica oleracea 
L. var.  capitata L.) in culture solutions containing 0, 0.5, 5, or 
25 mg Be/litre (as Be(NO3)2) with a low or high supply (20 or 200 
mg/litre) of calcium.  The dry weights of each part of the plant, 
especially of the inner leaves, decreased with increasing levels of 
beryllium.  A low calcium content increased this effect.  The 
critical content of beryllium that resulted in a 50% decrease in 
yield was estimated to be about 3000 mg/kg in the roots and 6 mg 
Be/kg dry weight in the outer leaves.  The latter value corresponded 
well with the "upper critical level" of 0.6 mg Be/kg dry weight in 
the leaves and shoots of spring barley,  Hordeum vulgare L. (Davis 
et al., 1978). 

    In soil culture, beryllium phytotoxicity is governed by the 
nature of the soil, particularly its cation-exchange capacity, and 
the pH of the soil solution.  Romney & Childress (1965) found that 
beryllium was strongly adsorbed by soils and bentonite, but not by 

kaolinite.  It displaced barium, calcium, magnesium, and strontium 
in various soil types and in bentonite.   With increasing acidity, 
beryllium became more soluble and hence more toxic to plants.  
Williams & Le Riche (1968) concluded that the diminished 
phytotoxicity under alkaline conditions was the result of 
precipitation of beryllium as a phosphate salt, making it 
unavailable to plants. 

    Kick et al. (1980) studied the effects of beryllium, 
administered as BeCl2, on the yields of plants.  Beryllium at 10 
mg/kg sandy soil reduced the yield of spring barley (kernels) by 
about 26%.  Addition to peat led to a yield reduction of 72 - 79%, 
whereas addition of kaolin diminished the yield-depressing effect 
of BeCl2. 

    Beryllium also suppressed the germination of cress seed 
( Lepidium sativum L.) at concentrations above 10-3 mol Be/litre (as 
BeCl2 and BeSO4 x 4H2O) at a pH of 5 - 6.  In addition, pigment 
analyses showed a reduction in chlorophyll content, which, 
however, was not correlated with beryllium concentrations (10-7 - 
10-3 mol/litre) in the solutions applied (Langhans, 1984). 

    The  mechanism  underlying  the  phytotoxicity  of  beryllium 
probably involves its inhibitory effects on enzyme activity and on 
the uptake of essential mineral ions.  As has been shown with 
animal phosphatases (section 8.7.1), beryllium in micromolar 
amounts also inhibits plant phosphatases (Hoagland, 1952b).  Romney 
& Childress (1965) noted inhibition of ribulose 1.5-diphosphate 
carboxylase and phosphoenolpyruvate carboxylase at concentrations 
above 1 µmol Be(NO3)2/litre.  The resulting interference with 
phosphorus metabolism is reflected by the enhanced phosphorus 
uptake observed in pea plants (Lebedena, 1960) and increased 
phosphorus concentrations in the tissues of alfalfa, barley, pea, 
and lettuce plants (Romney & Childress, 1965).  Conversely, uptake 
of calcium was reduced in all plant parts, particularly in the 
roots.  Uptake of Na, K, Fe, and Mn was not influenced in these 
plants.  However, in bush beans grown in nutrient solutions, leaf 
concentrations of these elements and of Cu, Zn, B, Al, Si, Mo, Sr, 
and Ba were decreased by high beryllium concentrations (8 - 16 
mg/litre as BeCl2) (Romney et al., 1980). 

    Encina & Becerra (1986) studied the effects of beryllium on 
cytokinesis in onion root tips.  BeCl2 at concentrations ranging 
from 3 - 10 mmol/litre was found to slightly inhibit cytokinesis.  
Induction of binucleate cells attained 2% at 10 mmol/litre.  At 
higher concentrations, production of binucleate cells clearly 
decreased, probably because beryllium slowed down the rate of 
telophase and the mitotic index.  Beryllium may displace calcium 
from its binding site, hence prohibiting the formation of cell 
plates.  This hypothesis was confirmed by the finding that, at 
higher calcium levels, the specific inhibiting effect of beryllium 
was negated. 

7.3.2  Animals

    No data are available on the effects of beryllium on domestic 
or wild terrestrial animals in the environment. 


8.1  Single exposures

    The acute toxicity of beryllium was first described by Siem 
(1886) who observed that the toxicity of subcutaneously injected 
beryllium in cats, dogs, and rabbits was ten times higher than that 
of aluminium. 

    Acute toxicity data for different beryllium compounds in 
experimental animals are summarized in Table 10.  The LD50 data 
show the low toxicity of ingested beryllium, compared with that of 
parenterally administered beryllium.  This is because of intestinal 
precipitation of beryllium as nonabsorbable phosphate. 

    Signs of acute beryllium poisoning, which were observed in LD50 
studies, were respiratory disorders, spasms, hypoglycaemic shock, 
and respiratory paralysis (Kimmerle, 1966).  Hypoglycaemia was 
attributable to liver necrosis caused by beryllium.  Aldridge et 
al. (1949) observed severe midzonal liver necrosis, 1 - 2 days 
after administration of lethal doses of beryllium. 

    Melnikov (1959) determined an LC50 of 3 mg Be/m3 for mice, 
following a 2-h inhalation exposure to beryllium acetate mist.  
Signs of poisoning were coughing, inflammation of the mucous 
membranes, dyspnoea, and marked cyanosis before death.  Pathological
examination revealed diffuse oedema in lung tissue, occasional
desquamative pneumonia, and marked degenerative and proliferative
changes in the liver, kidneys, and spleen. 

    The toxicity of ash from the burning of coal (section 3.1) with 
a relatively high beryllium content was described by Jirele et al. 
(1966). This initiated a series of studies concerned with the 
immunotoxicity and toxicokinetics of this metal in Czechoslovakia. 

    By means of cell kinetic studies and histopathological 
examination, Sendelbach et al. (1986) determined the acute response 
in the lungs of mice and rats exposed to an aerosol of BeSO4 (13 
mg/m3, 1 h). 
Table 10.  Acute toxicity of beryllium compounds (LD50 values 
expressed as mg Be/kg body weight)
Compound/    Route of          LD50     Reference
animal       administrationa 
 Beryllium acetate
Rat          ip                22.4     Venugopal & Luckey (1978)
 Beryllium carbonate
Guinea-pig   ip                1.2      Venugopal & Luckey (1978)
 Beryllium chloride
Guinea-pig   ip                6.3      Cochran et al. (1951)
Mouse        im                1.3      Venugopal & Luckey (1978)

Table 10 (contd.)
Compound/    Route of          LD50     Reference
animal       administrationa 
 Beryllium chloride (contd.)
Mouse        ip                0.15     Bianvenu et al. (1963)
Rat          ip                0.6      Cochran et al. (1951)
Rat          oral              9.8      Venugopal & Luckey (1978)

 Beryllium fluoride
Mouse        iv                0.34     Kimmerle (1966)
Mouse        oral              19.1     Kimmerle (1966)
Mouse        sc                3.8      Kimmerle (1966)
 Beryllium hydroxide
Rat          iv                0.8      Venugopal & Luckey (1978)
 Beryllium nitrate
Guinea-pig   ip                3.48     Hyslop et al. (1943)
Mouse        iv                0.5      Kimmerle (1966)
Mouse        sc                10.8     Kimmerle (1966)
 Beryllium phosphate
Mouse        iv                1.4      Venugopal & Luckey (1978)
Rat          iv                0.36     Venugopal & Luckey (1978)
Rat          oral              6.5      Venugopal & Luckey (1978)
 Beryllium sulfate
Chicken      iv                4.8      Krampitz et al. (1978)
Chicken      sc                3.7      Krampitz et al. (1978)
Monkey       iv                0.05     Venugopal & Luckey (1978)
Mouse        iv                0.04     White et al. (1951)
Mouse        oral              6.95     Venugopal & Luckey (1978)
Mouse        sc                0.13     Morimoto (1959)
Rat          ip                1.54     Sutton (1939)
Rat          iv                0.62     Scott (1948)
Rat          oral              7.02     Venugopal & Luckey (1978)
Rat          sc                0.13     Morimoto (1959)
a  im=intramuscular; ip=intraperitoneal; iv=intravenous; 

   The animals did not exhibit any external effects during the 
observation period of 21 days.  On histopathological examination, 
rat lungs showed three times greater cellular proliferation than 
those of mice.  The differential cell counts indicated that there 
was endothelial and epithelial cell injury and an increase in 
interstitial cells in rats, whereas the predominating cell 
populations in mice were alveolar macrophages and interstitial and 
endothelial cells.  Histopathological changes were also more severe 
in rats.  The interstitium was thickened with infiltrated 
interstitional macrophages and segmented leukocytes.  Three weeks 
after exposure, this response was largely resolved. 

    Bencko et al. (1979b) induced experimental berylliosis in 
female rats.  Five months after intratracheal instillation of 0.1 
mg of beryllium oxide, the lesions were confirmed by 
histopathological study, and by positive migration inhibition tests 

on macrophages derived from splenic fragments.  When the animals 
were mated, 6 weeks after administration, and the F1 generation was 
tested for genetic transmission of beryllium hypersensitivity, the 
results of the migration inhibition test were negative. 

   Rats and hamsters were exposed to an aerosol of beryllium oxide 
(BeO) calcined at 1000 °C (Sanders et al., 1975).  The duration of 
single nose-only exposures ranged from 30 to 180 min.  Eight months 
after exposure, some granulomatous lesions were seen in rats 
exposed to the highest dose (100 µg Be/m3).  The macrophages 
assumed a foamy appearance within a month of exposure.  BeO caused 
a significant depression in the alveolar clearance of a test 
aerosol (239PuO2). 

8.2  Short- and long-term exposures

8.2.1  Short-term exposure  Oral

    By adding large quantities of beryllium carbonate (1250 - 2000 
mg/kg food) to a normal diet, Guyatt et al. (1933) produced rickets 
(rachitis) in young rats after 24 - 28 days on the diet.  The bone 
lesions observed were not a direct effect of beryllium itself, but 
were due to intestinal precipitation of beryllium phosphate and 
concomitant phosphorus deprivation.  Inhalation

    Acute chemical pneumonitis occurred in various animal species 
following the inhalation of beryllium metal or different beryllium 
compounds (Stokinger, 1981).  Repeated, daily, 6-h exposures to 
beryllium sulfate mist (mean concentration 47 mg BeSO4 x 6H2O/m3 or 
2 mg Be/m3) were lethal for goats (100% deaths), guinea-pigs (60%), 
monkeys (100%), rats (90%), dogs (80%), cats (80%), rabbits (10%), 
hamsters (50%), and mice (10%).  Death occurred within the first 
week in the goats, guinea-pigs, and monkeys, in the second or third 
week in the rats, and after one or two months in the dogs and cats.  
Exposure to 0.95 mg BeSO4 x 6H2O/m3 (0.04 mg Be/m3), over 100 days, 
did not lead to any deaths in the species tested (Stokinger et al., 
1950a).  Beryllium fluroide was more toxic than the sulfate.  
Inhalation of 1 mg BeF2/m3 (0.19 mg Be/m3) caused lung lesions in 
cats, dogs, rabbits, and rats that were similar to those produced 
by 10 mg BeSO4 x 6H2O/m3 (0.42 mg Be/m3).  The lesions in the lungs 
closely resembled those in man, but were not identical.  They were 
most severe and extensive in dogs, minimal in rats, and intermediate 
in cats and rabbits (Stokinger et al., 1950b, 1953). 

    In addition to pulmonary injuries, a macrocytic anaemia was 
observed in dogs and rabbits, with a tendency in dogs to return to 
a normal blood pattern, despite continued exposure (Stokinger et 
al., 1950a). 

    To compare the biological action of highly soluble beryllium 
fluoride (BeF2) and beryllium sulfate (BeSO4) with that of the 

poorly soluble beryllium phosphate (BeHPO4), Schepers (1964) 
exposed monkeys, 4 in each group, to aerosols of these compounds 
for 7 - 30 days, at a concentration of approximately 200 µg Be/m3.  
BeF2 proved most toxic and BeHPO4 least toxic.  The initial 
response was a marked anorexia in the BeF2 group, and a moderate to 
slight loss of appetite in the 2 other exposure groups.  Dyspnoea, 
a typical sign of human chronic beryllium disease, constituted 
another striking sign, particularly in the animals exposed to BeF2.  
Moderate recovery was noted, though, after cessation of exposure, 
some animals died.  In another study, mortality was 100% in monkeys 
exposed to high beryllium phosphate concentrations of around 1140 
and 8380 µg Be/m3. 

    The histological picture resembled that in other experimental 
animals and in human beings.  Pulmonary oedema and congestion and 
marked changes in the liver, kidneys, adrenals, pancreas, thyroid, 
and spleen were found in the animals exposed to BeF2 and the higher 
concentrations of BeHPO4.  Granulomas were noted in some monkeys, 
but, unlike the sarcoidotic lesions characteristic for man, they 
were of simple composition and confined to local lesions within the 
alveolar walls (Schepers, 1964). 

    Insoluble beryllium compounds can also produce acute 
pneumonitis.  Hall et al. (1950) found that the toxicity of inhaled 
BeO depended on the physical and chemical properties of the 
compound, notably ultimate particle size, state of aggregation, and 
solubility, which, in turn, were governed by the production 
conditions.  Two high-fired BeO grades (1350 °C and 1150 °C) did 
not produce pulmonary damage in dogs, guinea-pigs, cats, or rats, 
exposed for up to 360 h to concentrations of up to 88 mg BeO/m3 (32 
mg Be/m3).  However, exposure to low-fired BeO (400 °C), at 10 mg 
BeO/m3 (3.6 mg Be/m3) for 40 days, caused mortality in rats and 
marked lung damage in dogs, apparently because of its smaller 
ultimate particle size and lesser degree of aggregation compared 
with the high-fired grades.  Crossmon & Vandemark (1954) and 
Spencer et al. (1968) confirmed these results.  Other

    Cloudman et al. (1949) observed symptoms of osteosclerosis in 
the form of irregular thickening of the cortices of the long bones, 
pelvis, and skull of rabbits, 94 days after repeated intravenous 
injections of a total of 17 mg Be as zinc beryllium silicate. 

8.2.2  Long-term exposure  Oral

    The low bioavailability and, hence, toxicity of ingested 
beryllium was confirmed by Schroeder & Mitchener (1975 a,b).  
Exposure of rats and mice to beryllium, in the form of beryllium 
sulfate in the drinking-water (5 mg Be/litre), did not show any 
effects on life span and survival.  Only slight effects on the body 
weight of female mice occurred.  A mild weight depression was also 

the only response observed in rats receiving the highest dietary 
concentration (500 mg BeSO4/kg) in a 2-year feeding study 
(Morgareidge et al., 1977).  Inhalation

    The characteristic non-malignant response to long-term, low-
level, inhalation exposure to soluble and insoluble beryllium 
compounds is chronic pneumonitis associated with granulomas 
(Stokinger, 1981).  However, as with short-term exposure, the 
beryllium granulomatosis observed in experimental animals only 
partly corresponds with the chronic disease in human beings. 

    In the early studies of Policard (1948; 1949a; 1949b; 1950a; 
1950b), temporary nodular granulomas were observed in the lungs of 
guinea-pigs exposed to dusts of BeO, NaBeF3, Be(OH)2, beryl, or 
elemental beryllium.  Since inhalation of pure beryllium or beryl 
dust only produced a temporary pulmonary reaction without formation 
of granulomas, the fluoride (NaF), which was present in the 
beryllium compounds administered, was believed to be the causative 
agent.  However, later studies established that beryllium itself 
caused the pulmonary changes. 

    Schepers et al. (1957) exposed rats to a BeSO4 aerosol (Table 
11) daily, for up to 6 months, and found that the characteristic 
response was a stimulation of epithelial cell proliferation without 
any formation of fibrotic tissue.  Six main pulmonary reactions 
occurred during the 6 months following cessation of exposure: 
formation and clustering of foamy macrophages; infiltration of the 
alveolar walls; lobular septal cell proliferation; epithelialization 
of the peribronchial alveolar walls; granulomatosis with a central 
core of large macrophages and a superficial thin zone of plasma 
cells; and neoplasia.  A similar picture was seen in various long-
term studies summarized in Table 11. 

    In a study by Wagner et al. (1969), the inhalation toxicities 
of beryl and bertandite aerosols were compared at the "nuisance 
limit" for all dusts (15 mg/m3) in  rats, hamsters, and monkeys.   
At  this particle concentration, the beryllium contents of the 
aerosols were 620 and 210 µg/m3 for beryl and bertrandite,   
respectively.  Exposure was continued intermittently for 17 months.  
Pulmonary neoplasia was produced in the beryl-exposed rats, 
whereas, in the bertrandite-exposed rats and in all other species, 
the lesions were characterized as atypical proliferation and/or 
granulomatous inflammation.  The importance of genetic 
predisposition was demonstrated by Barna et al. (1984) who 
administered single doses of 10 mg BeO intratracheally to 2 
commercial strains of guinea-pigs.  Granulomatous lung disease 
occurred in all the animals in one strain, but not in the other. 

8.3  Skin irritation and sensitization

    Dutra (1951) implanted beryllium compounds and metallic 
beryllium in the subcutaneous tissues at 12 sites on the side of a 
pig.  Beryllium granulomas similar to those observed in human 
beings were produced. 

Table 11.  Non-malignant pulmonary changes in experimental animals after long-term inhalation 
exposure to beryllium compounds
Species   Beryllium   Concentration   Maximum        Non-malignant pulmonary changes        Reference
          compound    (µg Be/m3)      exposure
Rat       BeSO4       36              26 weeks       Foam-cell clusters; focal mural        Schepers
                                      (8 h/day;      infiltration; lobular septal cell      et al. 
                                      5.5 day/week)  proliferation; peribronchial alvelor   (1957)
                                                     wall epithelialization; 

Rat       BeSO4       2.8             80 weeks       No specific inflammatory abnormalties  Vorwald 
                      21              (7 h/day;      Inflammatory changes in long-          et al.
                                      5 day/week)    surviving rats                         (1966)
                      42                             Chronic pneumonitis; focal
                                                     granulomatous lesions
                      194                            Acute disease

Rat       BeSO4       34              72 weeks       Increase in lung weight; inflammatory  Reeves
                                      (7 h/day;      and proliferative changes; clusters    et al.
                                      5 day/week)    of macrophages in alveolar spaces;     (1967)
                                                     occasionally granulomatosis and 

Rat       Bertrand-   210             73 weeks       Granulomatous legions; lymph nodes     Wagner
          ite                         (6 h/day;      composed of dust-laden macrophages     et al.
                                      5 day/week)                                           (1969)

Rat       Beryl       620             73 weeks       Atypical cell proliferations; loose    Wagner
                                      (6 h/day;      collections of foamy macrophages; no   et al.
                                      5 day/week)    granulomatous lesions                  (1969)

Hamster   Bertrand-   210             73 weeks       Few granulomatous lesions; atypical    Wagner
          ite                         (6 h/day;      proliferations                         et al.
                                      5 day/week)                                           (1969)

Hamster   Beryl       620             73 weeks       No granulomatous lesions; atypical     Wagner
                                      (6 h/day;      cell proliferations                    et al.
                                      5 day/week)                                           (1969)

Table 11 (contd.)
Species   Beryllium   Concentration   Maximum        Non-malignant pulmonary changes        Reference
          compound    (µg Be/m3)      exposure
Monkey    BeSO4       35              unknown        Pneumonitis; granulomatosis            Vorwald et
                                                                                            al. (1966)

Monkey    Bertrand-   210             99 weeks       Clusters of dust-loaded macrophages,   Wagner et
          ite                         (6 h/day;      lymphocytes and plasma cells; no       al. (1969)
                                      5 day/week)    other marked changes                             

Monkey    Beryl       620             99 weeks       Clusters of dust-loaded macrophages,   Wagner et 
                                      (6 h/day;      lymphocytes and plasma cells; no       al. (1969)
                                      5 day/week)    other marked changes                             

Monkey    BeO         3300-4400       30 min/month   No major changes                       Conradi et
          (1400 °C)                   (3 times)                                             al. (1971)

Dog       BeO         3300-4400       30 min/month   No major changes                       Conradi et
          (1400 °C)                   (3 times)                                             al. (1971)
    Cutaneous hypersensitivity occurred in guinea-pigs after intra-
dermal injection of soluble beryllium compounds (Alekseeva, 1966).  
These findings were confirmed by other studies described in section 

8.4  Reproduction, embryotoxicity, and teratogenicity

    Puzanova et al. (1978) injected BeCl2 subgerminally in chicken 
embryos at early stages of embryogenesis.  Doses exceeding 0.3 µg 
were embryo-lethal; doses of 0.03 - 0.3 µg were not lethal, but 
caused malformations consisting of malposed and malformed heart and 
caudal regression, body wall aplasia, symptoms of the strait jacket 
syndrome, and malformations of the mandible and facial clefts. 

   In a study on the transplacental absorption of beryllium (section 
6.2), Bencko et al. (1979a) found that beryllium penetration through 
the placenta was relatively poor, depending on the time of 
administration.  After intravenous administration of 0.1 mg BeCl2/kg 
body weight on the 14th day of pregnancy, mouse fetuses contained an 
average of 0.0013 mg Be/kg, which was about one order of magnitude 
higher than the relative beryllium content of 0.0002 mg/kg, found 
after administration on the 7th day of pregnancy. 

   Tsujii & Hoshishima (1979) studied the behaviour of the offspring 
of mice exposed to beryllium sulfate during pregnancy.  Six female 
CFW strain mice received 11 intraperitoneal injections of BeSO4 (140 
ng Be/mouse per day) during pregancy.  The behaviour of the 
offspring differed from that of the control animals as follows:  
delayed response in head turning in a geotaxis test, acceleration in 
a straight-walking test, delayed bar-holding response, acceleration 
of bar holding. 

    The effects of beryllium nitrate on early and late pregnancy in 
rats were investigated by Mathur et al. (1987).  When beryllium was 
injected intravenously at a dose of 0.316 mg/kg body weight on day 1 
of pregnancy, implantation and late pregnancy phase were not 
affected.  Pups, which appeared to be normal when delivered, died 
after 2 - 3 days, probably due to the toxic effects of beryllium.  
When beryllium was administered on day 11 following mating, all the 
fetuses were resorbed because of the immediate entry of beryllium 
into  the  fetal  circulation.  Administration  of  beryllium  after  
the formation of the placenta, i.e., after day 12, prevented the 
fetal resorption. 

8.5  Mutagenicity and related end-points

8.5.1  DNA damage

    Kubinski et al. (1977,1981) reported that salts of beryllium (30 
µmol/litre) induced complexes between DNA and proteins in 
 Escherichia coli cells and Ehrlich ascites cells, suggesting an 
interaction of beryllium with DNA. 

    The beryllium ion also seems to bind to DNA polymerases, since 
beryllium chloride caused a dose-related (2 - 10 mmol/litre) 

reduction in the accuracy of DNA synthesis in an  in vitro assay 
using purified DNA polymerase from avian myeloblastosis virus 
(Sirover & Loeb, 1976). 

    Divalent beryllium was also found to increase misincorporation 
of nucleoside triphosphates during polymerization of poly-d (A-T) by 
 Micrococcus luteus DNA polymerase (Luke et al., 1975).  Associated 
with this effect was a strong inhibition of one of the two 
exonuclease activities of this enzyme.  An increase in 
misincorporation was also reported by Zakour et al. (1981). 

    In the  E. coli pol+/pol- assay for DNA-modifying effects, 
beryllium sulfate was inactive, with or without an S-9 activation 
system (Rosenkranz & Poirier, 1979). 

    In the hepatocyte primary culture/DNA repair test, beryllium 
sulfate tetrahydrate (0.1 - 1 g /litre) was negative (Williams et 
al., 1982). 

8.5.2  Mutation  Bacteria and yeast

    Beryllium sulfate was not mutagenic in several bacterial 
mutation assays.  In the  Salmonella typhimurium test, frequency of 
the backward mutations was not significantly enhanced in the most 
commonly used strains (TA 1535, TA 1536, TA 1537, TA 98, TA 100) 
(Rosenkranz & Poirier, 1979; Simmon, 1979a). 

    Simmon et al. (1979) tested beryllium sulfate in the host-
mediated assay with different  Salmonella strains (TA 1530, TA 1535, 
TA 1538) and  Saccharomyces cerevisiae D3.  Beryllium sulfate given 
to mice either orally (1200 mg/kg) or by intramuscular injection (25 
mg/kg) was not mutagenic. 

    Beryllium chloride (10 mmol/litre) produced a weak mutagenic 
response in the  Bacillus subtilis rec. assay (Kanematsu et al., 
1980).  However, no effect was noted in another rec. assay using 50 
mmol beryllium chloride/litre (Nishioka, 1975).  McCann et al. 
(1975) hypothesized that the large amounts of magnesium salts, 
citrate, and phosphate in the minimal medium of bacterial tests may 
preclude the entry of beryllium into bacteria.  The negative 
mutagenic response of beryllium sulfate in the mitotic recombination 
assay with  Saccharomyces cerevisiae strain D3 (Simmon, 1979b) may 
also be due to reduced penetration of beryllium into the cells.  Cultured mammalian cells

    Beryllium caused gene mutations in cultured mammalian cells.  At 
concentrations of 2 and 3 mmol/litre, beryllium chloride enhanced 
the induction of 8-azaguanine-resistant mutants in the Chinese 
hamster V79 cells 6-fold compared with control values.  The 
underlying mutation resulted in a deficiency in the activity of the 
enzyme hypoxanthine guanine phosphoribosyl transferase (Miyaki et 
al., 1979).  Hsie et al. (1979a,b) reported similar results using 
beryllium sulfate. 

8.5.3  Chromosomal effects

    Beryllium caused marked chromosomal aberrations in cultured 
mammalian cells.  Talluri & Guiggiani (1967) reported that beryllium 
chloride (0.5 - 10 mmol/litre) caused stickiness, chromatid gaps and  
breaks,  fragments,  and mitotic delay  in  cultured  peripheral 
lymphocytes and primary kidney cells of the domestic pig. 

    Beryllium sulfate (0.03 mmol/litre) was clastogenic (i.e., 
chromosome-breaking) in Syrian hamster embryo cells with 19% 
aberrations in the treated cells compared with 1.5% in the controls 
(Larramendy et al., 1981).  In the same study, a clear clastogenic 
potential of beryllium in human lymphocytes was noted, though it was 
less marked than in the animal cells. 

    Paton & Allison (1972) did not find any chromosomal aberrations 
with 1 x 10-5 and 1 x 10-3 mmol beryllium sulfate/litre in human 
diploid fibroblasts and human leukocytes  in vitro. 

    Larramendy et al. (1981) reported a dose-related increase in 
sister chromatid exchanges in both Syrian hamster embryo cells and 
human  lymphocytes.   The  exchange  frequency  in  the  human 
lymphocytes was  11.30 ± 0.60,  17.75 ± 1.10,  18.15 ± 1.79,  and 
20.7 ± 1.01 at BeSO4 concentrations of 0 µg/ml (control), 1 µg/ml, 
2.5 µg/ml, and 5 µg/ml culture medium.  Similar data were found for 
the animal cells. 

    There are no  in vivo data on the clastogenic potential of 

8.6  Carcinogenicity

8.6.1  Bone cancer

    Gardner & Heslington (1946) investigated the carcinogenic 
properties of beryllium.  Osteosarcomas of the long bones developed  
in 7 rabbits that survived 7 or more months after the intravenous 
injection of zinc beryllium silicate (ZnBeSiO3) (which is used in 
the fluorescent light tube industry).  Both zinc oxide and zinc 
silicate alone were inactive, while beryllium oxide (firing 
temperature unstated) was also carcinogenic (Table 12). 

    Several investigators reproduced beryllium bone sarcoma in the 
rabbit with beryllium metal and various beryllium compounds (Table 
12).  Intraveneous injection or intramedullary injection, in which 
beryllium was directly introduced into the medullary cavity of 
bones, were used in most of these studies. 

    In one study, osteosarcomas were found in mice after 20 - 22, 
twice-weekly, intravenous injections of zinc beryllium silicate; 
beryllium oxide did not induce any effects (Cloudman et al., 1949).  
The numbers of mice and incidence of tumours were not stated. 

    Guinea-pigs and rats did not develop bone cancer after intravenous 
injection of both zinc beryllium silicate and beryllium oxide (Gardner 
& Heslington, 1946). 

Table 12.  Osteosarcoma from berylliuma
Compoundb    Species      Total     Mode of             Incidence    Incidence    Reference
                          dose      administrationc     of tumours   of
                          (mg Be)                                    metastases
ZnBeSiOx     rabbit       60        iv in 20 doses      7/7 (100%)   3/7 (43%)    Gardner &
BeO          rabbit       360       iv in 20 doses      unknown      unknown      Heslington
ZnBeSiOx     guinea-pig   60        iv in 20 doses      0            -            (1946)
BeO          guinea-pig   360       iv in 20 doses      0            -
ZnBeSiOx     rat          60        iv in 20 doses      0            -
BeO          rat          360       iv in 20 doses      0            -

ZnBeSiOx     rabbit       17        iv in 20-22 doses   4/5 (80%)    3/4 (75%)    Cloudman et
BeO          rabbit       140       iv in 20-22 doses   0            -            al. (1949)
ZnBeSiOx     mouse        0.26      iv in 20-22 doses   unknown      unknown
BeO          mouse        0.55      iv in 20-22 doses   0            -

ZnMnBeSiOx   rabbit       3.7-7.0   iv in 1-30 doses    3/6 (50%)                 Hoagland et
ZnMnBeSiOx   rabbit       10-12.6   iv in 1-30 doses    3/4 (75%)    5/7 (71%)    al. (1950)
BeO          rabbit       360       iv in 1-30 doses    1/9 (11%)

ZnBeSiOx     rabbit       7.2       iv in 6 doses       4/14 (29%)   2/4 (50%)    Barnes et
ZnBeSiOx     rabbit       15        iv in 10 doses      2/3 (67%)    1/2 (50%)    al. (1950)
BeSiOx       rabbit       180       iv in 6-10 doses    1/11 (9%)    0/1

ZnBeSiOx     rabbit       64-90     iv in 17-25 doses   2/3 (67%)    2/2 (100%)   Dutra &
BeO          rabbit       360-700   iv in 20-26 doses   6/6 (100%)   6/6 (100%)   Largent 

ZnBeSiOx     rabbit       12        iv in 20 doses      5/10 (50%)   > 2/5 (40%)  Janes et
                                                                                  al. (1954)

ZnBeSiOx     rabbit       12        iv in 20 doses      10/13 (77%)  unknown      Kelly et 
BeO          rabbit       360       iv                  unknown      2/3 (66%)    Komitowski

BeO          rabbit       79-144    IMD                 7/9 (78%)    unknown      Yamaguchi
BeO          rabbit       151-216   IMD                 11/11 (100%) unknown      (1963)

ZnBeSiO3     rabbit       0.144     IMD                 4/12 (33%)   3/4 (75%)    Tapp (1969)

BeO          rabbit       1 mg/m3   inhalation:         0/5          -            Dutra et
                          6 mg/m3   25 h/week, 9-13     1/6          1/1          al. (1951)
                          30 mg/m3  months              0/8          -
a  Adapted from: Reeves (1979) and Groth (1980).
b  ZnBeSiOx = zinc beryllium silicate; ZnMnBeSiOx = zinc manganese beryllium silicate;
   BeO = beryllium oxide; BeSiOx = beryllium silicate.
c  IMD = intramedullary; iv = intravenous.

    As shown in the summary table (Table 12), the incidence of 
tumours was consistently high in the rabbit studies, varying from 13 
to 100%.  The latent period varied from 5.5 to 24 months after the 
last injection of beryllium (Groth, 1980). The osteosarcomas 
developed in different bones, including the humerus, tibia, femur, 
ilium, ischial tuberosity, lumbar vertebra, scapula, and ribs.  
Frequently, two or more bones were affected in the same animal.  
Metastases occurred in 40 - 100% of the animals, most frequently in 
the lungs, but also in the liver, kidney, omentum, skin, and lymph 
nodes (Groth, 1980). 

    The cell types of the bone tumours were described as 
osteoblastic, chondroblastic, and fibroblastic, and differed from 
animal to animal, with all 3 cell types occurring frequently in the 
same tumour (Kelly et al., 1961).  Tapp (1969) characterized the 
sarcomas as chondrosarcomatous or anaplastic.  The metastases 
appeared to be similar in all respects to the primary tumours and 
contained osseous tissue (Barnes et al., 1950; Dutra & Largent, 
1950; Dutra et al., 1951).  The metastatic osteogenic sarcomas 
developing in the lungs could easily be distinguished from primary 
lung neoplasms. 

8.6.2  Lung cancer

    Vorwald (1953) first reported experimental evidence for 
pulmonary tumours induced by beryllium.  These observations were 
confirmed in several studies on rats following the inhalation of 
beryllium sulfate, oxide, phosphate, fluoride, or beryl ore.  
Positive results were also seen after intratracheal injection of 
beryllium sulfate, oxide, metal, and various beryllium alloys.  
Pulmonary carcinomas were produced in monkeys following inhalation 
of beryllium sulfate and phosphate and after intrabronchial 
implantation of a beryllium oxide suspension.  No pulmonary 
neoplasms were found in carcinogenicity studies on rabbits, guinea-
pigs, or hamsters.  The results of the various inhalation and 
intratracheal/intrabronchial studies are summarized in Tables 13 
and 14. 

    The  tumours  observed  in  rats  were  usually  adenocarcinomas 
(Vorwald, 1953; Schepers et al., 1957; Reeves et al., 1967).  Some 
of the tumours developed metastases to tracheobronchial lymph nodes 
and pleura (Vorwald, 1953) and to the adrenals, kidneys, liver, 
pancreas, and brain (Schepers, 1961). 

    While bertrandite did not produce cancer, beryl ore caused 
pulmonary adenomas, adenocarcinomas, and epidermoid carcinomas in 
rats (Wagner et al., 1969).  This difference is not explained by 
the lower beryllium concentration in the bertrandite-exposure 
group, since much lower absolute beryllium concentrations showed 
positive results (Table 13). 

Table 13.  Pulmonary cancer after inhalation exposure to berylliuma
Species      Compound     Atmospheric       Duration of exposure         Incidence of   Referenced
                          concentration                                  pulmonary
                          (Be)                                           carcinomas
Rat          BeSO4        33-35 µg/m3       12-24 months, 33-38 h/week   4/8            Vorwald (1953)*
Rat          BeSO4        33-35 µg/m3       13-18 months, 33-38 h/week   17/17          Vorwald et al. (1955)**
Rat          BeSO4        55 µg/m3          3-18 months, 33-38 h/week    55/74          Vorwald (1962)*
Rat          BeSO4        180 µg/m3         12 months, 33-38 h/week      11/27          Vorwald (1962)*
Rat          BeSO4        18 µg/m3          3-22 months, 33-38 h/week    72/103         Vorwald (1962)*
Rat          BeSO4        18 µg/m3          8-21 months, 33-38 h/week    31/63          Vorwald (1962)*
Rat          BeSO4        18 µg/m3          9-24 months, 33-38 h/week    47/90          Vorwald (1962)*
Rat          BeSO4        18 µg/m3          11-16 months, 33-38 h/week   9/21           Vorwald (1962)*
Rat          BeSO4        1.8-2.0 µg/m3     8-21 months, 33-38 h/week    25/50          Vorwald (1962)*
Rat          BeSO4        1.8-2.0 µg/m3     9-24 months, 33-38 h/week    43/95          Vorwald (1962)*
Rat          BeSO4        1.8-2.0 µg/m3     13-16 months, 33-38 h/week   3/15           Vorwald (1962)*
Rat          BeO          9000 µg/m3        3-12 months, 33-38 h/week    22/36          Vorwald (1962)*
Rat          BeSO4        21-42 µg/m3       18 months, 33-38 h/week      almost 100%b   Vorwald et al. (1966)*
Rat          BeSO4        2.8 µg/m3         18 months, 33-38 h/week      13/21          Vorwald et al. (1966)*
Rat          BeSO4        32-35 µg/m3       6-9 months, 44 h/week        58/136c        Schepers et al. (1957)**
Rat          BeHPO4       32-35 µg/m3       1-12 months                  35-60/170      Schepers (1961)*
Rat          BeHPO4       227 µg/m3         1-12 months                  7/40           Schepers (1961)*
Rat          BeF2         9 µg/m3           6-15 months                  10-20/200      Schepers (1961)*
Rat          ZnMnBeSiO3   850-1250 µg/m3    1-9 months                   4-20/200       Schepers (1961)*
Rat          BeSO4        34 µg/m3          13 months, 35 h/week         43/43          Reeves et al. (1967)
Rat          BeSO4        36 µg/m3          3 months, 35 h/week          19/22          Reeves & Deitch (1969)
Rat          BeSO4        36 µg/m3          6 months, 35 h/week          33/33          Reeves & Deitch (1969)
Rat          BeSO4        36 µg/m3          9 months, 35 h/week          15/15          Reeves & Deitch (1969)
Rat          BeSO4        36 µg/m3          12 months, 35 h/week         21/21          Reeves & Deitch (1969)
Rat          BeSO4        36 µg/m3          18 months, 35 h/week         13/15          Reeves & Deitch (1969)
Rat          BeO          400 µg/m3         4 months, 5 h/week           8/21           Litvinov et al. (1984)
Rat          BeO          30 µg/m3          4 months, 5 h/week           6/26           Litvinov et al. (1984)
Rat          BeO          4 µg/m3           4 months, 5 h/week           4/39           Litvinov et al. (1984)
Rat          BeO          0.8 µg/m3         4 months, 5 h/week           3/44           Litvinov et al. (1984)
Rat          BeCl2        400 µg/m3         4 months, 5 h/week           11/19          Litvinov et al. (1984)
Rat          BeCl2        30 µg/m3          4 months, 5 h/week           8/24           Litvinov et al. (1984)
Rat          BeCl2        4 µg/m3           4 months, 5 h/week           2/42           Litvinov et al. (1984)
Rat          BeCl2        0.8 µg/m3         4 months, 5 h/week           1/41           Litvinov et al. (1984)
Rat          beryl        620 µg/m3         17 months, 30 h/week         18/19          Wagner et al. (1969)
Rat          bertrandite  210 µg/m3         17 months, 30 h/week         0/30-60        Wagner et al. (1969)

Table 13 (contd.)
Species      Compound     Atmospheric       Duration of exposure         Incidence of   Referenced
                          concentration                                  pulmonary
                          (Be)                                           carcinomas
Rabbit       ZnMnBeSiO3   1000 µg/m3        24 months                    0              Schepers (1961)

Guinea-pig   ZnMnBeSiO3   100 µg/m3         22 months                    0              Schepers (1961)
Guinea-pig   BeSO4        35 µg/m3          12 months                    0              Schepers (1961)
Guinea-pig   BeSO4        3.7-30.4 µg/m3    18-24 months, 30 h/week      0/58           Reeves et al. (1972)

Hamster      beryl        620 µg/m3         17 months, 30 h/week         0/48           Wagner et al. (1969)
Hamster      bertrandite  210 µg/m3         17 months, 30 h/week         0/48           Wagner et al. (1969)

Monkey       BeSO4        38.8 µg/m3        >36 months, 15 h/week        8/11           Vorwald (1968)
Monkey       BeSO4        35-200 µg/m3      8 days, 6 h/day              0/4            Schepers (1964)
Monkey       BeF2         180 µg/m3         8 days, 6 h/day              0/4            Schepers (1964)
Monkey       BeHPO4       200 µg/m3         8 days, 6 h/day              0/4            Schepers (1964)
Monkey       BeHPO4       1100 µg/m3        8 days, 6 h/day              1/4            Schepers (1964)
Monkey       BeHPO4       8300 µg/m3        8 days, 6 h/day              0/4            Schepers (1964)
Monkey       beryl        620 µg/m3         17 months, 30 h/week         0/12           Wagner et al. (1969)
Monkey       bertrandite  210 µg/m3         17 months, 30 h/week         0/12           Wagner et al. (1969)
a  From: Reeves (1978), adapted and supplemented.
b  Number of animals not stated.
c  Number of tumour-bearing animals not stated; total number of tumours: 76.
d  These studies were not published as primary experimental publications, but were either quoted in
   reviews (*) or published as abstracts (**).  The documentation of experimental details, including
   verification of chamber exposure concentration values, is unavailable.  These figures, therefore, must
   be treated with caution.
Table 14.  Pulmonary cancer after intratracheal or intrabronchial injection of beryllium
Species      Compound     Total        Mode of          Autopsy        Incidence of  Reference
                          dose         administration   intervala      pulmonary
                          (Be)                                         carcinomas
Rat          ZnMnBeSiOx   0.46 mg      intratracheal    ns             0             Vorwald (1950)
Rat          BeO          0.338 mg     intratracheal    ns             1/4           Vorwald (1953)
                                       in 3 doses
Rat          BeSO4        0.033 mg     intratracheal    ns             1/5           Vorwald (1953)
                                       in 3 doses
Rat          BeO          9 mg         intratracheal    30-77 weeks    23/45         Spencer et al.
             (500 °C)                                                                (1968)
Rat          BeO          9 mg         intratracheal    30-69 weeks    3/19          Spencer et al.
             (1100 °C)                                                               (1968)
Rat          BeO          9 mg         intratracheal    32-97 weeks    3/28          Spencer et al.
             (1600 °C)                                                               (1968)
Rat          Be metal     2.5 mg       intratracheal    16-19 months   6/6           Groth et al. 
Rat          Be metal     0.5 mg       intratracheal    16-19 months   2/3           Groth et al. 
Rat          Be metal,    2.5 mg       intratracheal    16-19 months   4/4           Groth et al.
             passivated                                                              (1980)
Rat          BeAl alloy   1.55 mg      intratracheal    16-19 months   7/11          Groth et al.
Rat          BeAl alloy   0.3 mg       intratracheal    16-19 months   2/6           Groth et al.
Rat          4% BeCu      0.1 mg       intratracheal    16-19 months   0/11          Groth et al.
             alloy                                                                   (1980)
Rat          2.2 BeNi     0.056 mg     intratracheal    16-19 months   0/12          Groth et al.
             alloy                                                                   (1980)
Rat          2.4% BeCuCo  0.06         intratracheal    16-19 months   0/15          Groth et al.
             alloy                                                                   (1980)
Rat          BeO (900°C)  15 mg        intratracheal    18 months      7/29          Ishinishi et
                                       in 15 doses                                   al. (1980)

Rabbit       ZnMnBeSiOx   2.3-6.9 mg   intratracheal    ns             0             Vorwald (1950)

Table 14 (contd.)
Species      Compound     Total        Mode of          Autopsy        Incidence of  Reference
                          dose         administration   intervala      pulmonary
                          (Be)                                         carcinomas
Guinea-pig   ZnMnBeSiOx   3.4 mg       intratracheal    ns             0             Vorwald (1950)
Guinea-pig   Be stearate  5 mg         intratracheal    ns             0             Vorward (1950)
Guinea-pig   Be(OH)2      31 mg        intratracheal    ns             0             Vorwald (1950)
Guinea-pig   Be metal     54 mg        intratracheal    ns             0             Vorwald (1950)
Guinea-pig   BeO          75 mg        intratracheal    ns             0             Vorwald (1950)

Monkey       BeO          18-90 mg     bronchomural     ns             3/20          Vorwald (1968)
                                       implant &
a  ns = not specified.
    The physical and chemical properties of compounds of beryllium 
apparently determine their carcinogenic potential, as demonstrated 
by Spencer et al. (1968).  Three different samples of beryllium 
oxide, calcined at 500, 1100, or 1600  °C, respectively, were 
injected intratracheally into rats.  The results of all 3 studies 
were positive, but the incidence of pulmonary adenocarcinomas was 
highest after treatment with the low-fired BeO, where 23/45 or 51% 
of the rats developed carcinomas, compared with 3/19 or 16% and 
3/28 or 11% with the high-fired oxides.  In a later study (Spencer 
et al., 1972), BeO rocket exhaust product proved almost as 
carcinogenic as low-fired BeO. 

    Lung tumours were also produced in rats by intratracheal 
injection of beryllium metal, passivated beryllium metal, and a 
beryllium-aluminium alloy (62% beryllium) at doses of 0.3 - 2.5 mg 
Be/animal (Groth et al., 1980).  No tumours were seen after 
administration of other beryllium alloys.  However, the latter were 
injected in much lower doses (Table 14), possibly obscuring a 
carcinogenic potential of these compounds. 

    In a short-term inhalation study carried out by Schepers (1964), 
a small pulmonary neoplasm was found in 1 out of 20 rhesus monkeys 
exposed to 1.1 mg Be/m3 (BeHPO4) for 8 days and autopsied 82 days 
later.  BeSO4 and BeF2 were negative in the short-term, but after 
long-term exposure to 39 µg Be/m3, 8 out of 9 monkeys that had 
survived 6 or more years showed pulmonary tumours of various 
histological types, all metastazing to the mediastinal lymph nodes 
and some to the bone, adrenals, and liver (Vorwald, 1968). 

    From the data in Table 13 and Table 14 it appears that the 
induction of pulmonary cancer by beryllium is species-specific.  
While rats and, perhaps, monkeys are susceptible, no pulmonary 
tumours were observed in rabbits, hamsters, and guinea-pigs.  The 
latter were exposed to concentrations that were carcinogenic in 100% 
of exposed rats.  The reasons for this negative neoplastic response 
are not known.  Whether the cutaneous hypersensitivity to beryllium 
in guinea-pigs indicates that some form of cellular immunity may be 
a factor in determining the carcinogenic response to beryllium, 
remains unresolved (Reeves, 1978).  The increased incidence of bone 
sarcomas in splenectomized rabbits exposed to beryllium (Janes et 
al., 1954; 1956) seems to indicate the relevance of immunocompetence 
for the induction of beryllium cancer. 

8.7  Mechanisms of toxicity, mode of action

8.7.1  Effects on enzymes and proteins

    Beryllium is a potent inhibitor of various enzymes of phosphate 
metabolism, particularly of alkaline phosphatase.  DuBois et al. 
(1949) found that toxic effects of beryllium might involve 
interference with the biological functions of magnesium.  A 50% 
inhibition of magnesium-activated phosphatase activity in rat serum 
was seen at 1.8 x 10-6 mol/litre.  Addition of Mg2+ did not 
influence the inhibitory action of beryllium, indicating that 
beryllium has a much greater affinity for the enzyme than magnesium.  

Only at very high magnesium concentrations, i.e., at a magnesium/
beryllium ratio of 40 000:1, was a decrease in the beryllium-induced 
inhibition of the alkaline phosphatase activity in rabbit kidney 
noted (Aldridge, 1950). 

    Thomas & Aldridge (1966) found that, of various enzymes 
examined, only alkaline phosphatase and  phosphoglucomutase 
activities were inhibited by 10-6 mol BeSO4/litre, whereas the 
activities of acid phosphatase, phosphoprotein phosphatase, 
adenosine triphosphatase, glucose-6-phosphatase, polysaccharide 
phosphorylase, hexokinase, phosphoglyceromutase, ribonuclease, 
A-esterase, cholinesterase, and chymotrypsin were not inhibited at  
10-3 mol BeSO4/litre.  With phosphoglucomutase, inhibition was 
competitive with respect to magnesium.   However, once established, 
reversion of the inhibition could not be produced by adding 
magnesium.  Beryllium probably combines with the unphosphorylated 
enzymes, both alkaline phosphatase and phosphoglucomutase, thus, 
interfering with the competition of magnesium for the 
unphosphorylated enzyme. 

    Cummings et al. (1982) found that cytoplasmic and nuclear cyclic 
AMP-independent casein kinase I was inhibited by beryllium 
(BeSO4/sulfosalicylic acid (1:1) 10 µmol/litre) indicating that the 
phosphorylation of protein substrates is also inhibited by 
beryllium.  Possibly the impairment of key protein phosphorylation 
is the biochemical basis for many of the toxic and carcinogenic 
actions of beryllium (Skilleter, 1984). 

    A number of other enzymes are inhibited by beryllium, but 
usually at higher concentrations.  The action of beryllium on these 
enzymes might be through its combination with the substrate, 
depleting the enzyme of its usual magnesium-substrate complex, 
rather than a direct action on the enzymes (Thomas & Aldridge, 

    Beryllium inhibited the magnesium-dependent phosphatic acid 
phosphatase by 30% at 10-4 mol/litre and completely at 10-3  
mol/litre (Hokin et al., 1963). Alkaline phosphatase was inhibited 
by 50% at 10-3 - 10-6 mol/litre and adenosine triphosphatase, by 
22 - 35% at 10-3 mol/litre (Cochran et al., 1951), deoxythymidine 
kinase was inhibited by 50% at 10-4 mol/litre (Mainigi & Bresnick, 
1969);  and lactate dehydrogenase was inhibited by 65% at 10-3 
mol/litre (Schormüller & Stan, 1965). 

    Beryllium also blocked the tricarboxylic cycle by inhibiting the 
activity of malic, succinic, and alpha-ketoglutaric dehydrogenases.  
This occurred in the liver and lungs of rats after intramuscular 
administration of 0.22 mg Be/kg (BeSO4); addition of MgSO4 decreased 
the inhibition (Mukhina, 1967). 

    The induction of drug-metabolizing enzymes in rat liver was also 
inhibited by beryllium (Witschi & Marchand, 1971).  Intravenous 
injection of 5 x 10-4 mol Be/kg body weight in rats inhibited 
hepatic induction of acetanilide hydroxylase, aminopyrine 
demethylase, and tryptophan pyrrolase, indicating that beryllium can 
interfere with some gene transcription mechanisms. 

    Beryllium compounds react selectively only with certain proteins 
(Reiner, 1971), affecting the cellular distribution of the protein.  
In rats given 33 mg of beryllium by intratracheal injection, the 
protein contents of the microsomes in lung-tissue cells almost 
doubled compared with those in control animals, while no changes 
occurred in the nuclei or mitochondria (Vorwald & Reeves, 1959). 

    These observations were confirmed by Parker & Stevens (1979) who 
showed that, of the chromatin proteins in liver nuclei, it was only 
6 - 17% of the non-histones that bound beryllium, while the histones 
did not have any affinity for the metal ion. 

    The results of several studies indicate that the target for 
beryllium toxicity is the cellular DNA.  BeSO4 (10-3 mol/litre) 
inhibited cell division in the metaphase (Chèvremont & Firket, 
1951).  RNA biosynthesis was not affected.  Truhaut et al. (1968) 
found that BeSO4 caused preferential accumulation of radioberyllium 
in the nuclei of regenerating rat liver and an increase in the 
sedimentation constant of DNA. 

    Witschi (1970) noted inhibition of DNA synthesis by beryllium in 
regenerating rat liver.  This was probably a consequence of 
inhibition of enzymes that play a critical role in DNA replication, 
and not a result of the direct interaction of beryllium with 
enzymes, such as thymidine kinase or DNA polymerase.  However, Luke 
et al. (1975) found strong inhibition of DNA polymerase from 
 Micrococcus luteus.  Be2+ increased misincorporation of 
polydeoxyadenosylthymidine during polymerization and this effect was 
associated with a strong inhibition of the 3' - 5' exonuclease 

    Be2+ was the only one of several divalent cations that altered 
the accuracy of DNA synthesis using purified DNA polymerase from 
avian myeloblastosis virus (Sirover & Loeb, 1976).  It probably does 
not interact with the catalytically active Mg2+ sites on DNA 
polymerase, but with a non-catalytic site. 

    Beryllium salts have been shown to exhibit dose-dependent 
stimulation and inhibition of both murine lymphocyte and accessory 
cell activities  in vitro (Skilleter, 1986).  In sheep, both 
insoluble Be(OH)2 and chemically complexed Be caused a powerful 
immunoblast proliferation (Denham & Hall, 1988; Hall, 1988). 

8.7.2  Immunological reactions

    Beryllium hypersensitivity appears to be cell-mediated and of 
the delayed type.  Alekseeva (1966) injected 2.5 or 10 µg Be as the 
chloride intradermally in guinea-pigs that had been sensitized to 
beryllium 4 weeks earlier.  At the higher dose, marked inflammatory 
reactions were seen at the site of injection after a few days; at 
the lower dose, repeated injections were necessary to evoke 
reactions.  By transferring homogenates of lymphoid tissue from 
sensitized to unsensitized animals, the hypersensitivity to 
beryllium could be transferred.  Transferring serum proved negative 
in this respect.  The findings of Alekseeva (1966) were confirmed by 

other studies.  Chiappino et al. (1969) demonstrated that all 
cutaneous reactions to beryllium in guinea-pigs could be inhibited 
by injection of an anti-lymphocytic serum from rabbits.  Turk & 
Polak (1969) suppressed reactivity by intravenous injection of 
beryllium lactate, and Reeves et al. (1972) observed a suppressed 
cutaneous reactivity in guinea-pigs after inhalation exposure to 
beryllium.  Conversely, the intradermally treated animals developed 
less severe pulmonary lesions than normal animals. 

    The mode of administration and the properties of beryllium 
compounds influence the magnitude of the immunological response.  
Krivanek & Reeves (1972) sensitized guinea-pigs with the sulfate, 
the serum albuminate, the hydrogen citrate, and the 
aurintricarboxylate of beryllium.  The two latter complexes, in 
which beryllium is strongly bound and, thus, unavailable for 
interaction with the decisive molecule, did not produce any 
immunological reactions.  Surprisingly, serum beryllium albuminate 
evoked a stronger reaction than BeSO4.  It has been assumed that the 
beryllium ion acts as a hapten, and that the beryllium serum 
albuminate is either identical with, or very similar to, the 
complete antigen. 

    Vacher (1972) found that delayed hypersensitivity in the skin of 
guinea-pigs resulted only from skin contact with beryllium.  Thus, 
parenteral administration would not elicit immunological reactions.  
Moreover, only the forms of beryllium that are capable of producing 
a complex with skin constituents were immunogenic. 


9.1  General population exposure

    From the use pattern of beryllium it can be deduced that 
toxicologically relevant exposure to beryllium is largely confined 
to the work-place.  Only a few exposure situations have been 
reported for the general population, i.e., the use of mantle-type 
camp lanterns, the handling of broken fluorescent tubes, and the 
"neighbourhood" cases  with  indirect  exposure  outside  
beryllium-producing  or beryllium-processing plants. 

   First  recognized  in  1938  by  Gelman  (1938),  
"neighbourhood" cases  gained  considerable  interest  in  the  
1940s.   Several non-occupational cases in individuals living in 
the close vicinity of beryllium plants and "para-occupational" 
cases in beryllium workers' families were reported (section 5.2).  
By 1966, a total of 60 "neighbourhood" cases had been reported in 
the USA, 27 of which were related solely to contact with worker's 
clothes, 18 to air contact alone, and 13 to clothes plus air 
contact; for 2 cases, no exposure data were available (Hardy et 
al., 1967).  There were at least 3 children among these cases (Hall 
et al., 1959). 

    Eleven cases of chronic beryllium disease with symptoms similar 
to those found in beryllium workers (section 9.2) were diagnosed 
among residents in the close vicinity of a beryllium production 
plant in Ohio, USA (Eisenbud et al., 1949; Eisenbud, 1982).  In a 
retrospective investigation, Eisenbud et al. (1949) concluded that 
10 out of the 11 non-occupational cases lived within 1.2 km of the 
plant and that no members of their households had worked in the 
plant.  During a 10-week air-sampling period in 1948, average 
concentrations of beryllium at a distance of 1.2 km were found to 
range from 0.004 to 0.02 µg/m3.  Taking into account the operating 
history of the plant, it was estimated that beryllium 
concentrations could have been greater, in the past, by 
approximately a factor of 10.  It was assumed that "the lowest 
exposure that produced disease was greater than 0.01 µg/m3 and 
probably less than 0.1 µg/m3" (Eisenbud, 1982).  On  the  basis  of  
these  studies,  a  maximum ambient air level of 0.01 µg/m3 was 
recommended and adopted by some regulatory agencies (section 5.2). 

    One of the 11 cases lived about 2.8 km from the plant, but was 
exposed to beryllium through the work clothes of her husband, who 
had worked in the plant for 3 months (Eisenbud et al., 1949).  A 
similar case was reported by Hardy (1948).  The mother of a female 
worker in a fluorescent lamp plant came in contact with beryllium 
dust from her daughter's shoes and clothes.  Both mother and 
daughter developed chronic beryllium disease, which was fatal for 
the mother. 

    In one instance reported by Lieben & Williams (1969), the 
individuals affected lived far away from the beryllium plant, but 
had regularly visited a graveyard situated across the street from 
the beryllium refinery. 

    Once the potential health hazards of beryllium were recognized 
and accepted, highly improved emission control and hygiene measures 

were established in beryllium plants.  Hence, no "neighbourhood" 
cases have been reported in recent years. 

    Bencko et al. (1980) conducted an epidemiological  study on 
groups of people exposed occupationally (section and non-
occupationally (36 persons) to emissions from Czechoslovakian power 
plants that burned coal with a comparatively high beryllium 
content.  The average beryllium concentration in the ambient air 
(measured by the fluorometric method) in the vicinity of a power 
plant was 0.08 µg/m3.  Immunological changes, in terms of elevated 
levels of IgG and IgA, and increased levels of autoantibodies and 
antibodies against antigens obtained from organs of rats with 
experimental berylliosis, were found in comparison with a control 
group of healthy subjects who had no contact with beryllium or 
other industrial toxic agents.  These immune reactions can be 
considered to be signs of beryllium exposure. 

    Because of the high sensitization potential of beryllium in 
provoking contact allergies (section 9.2), the increasing use of 
beryllium in dentistry (section 3.3) may be important in terms of 
general population exposure (Bencko, 1989).  Schönherr & Pevny 
(1985) presented 9 cases of a patch test-positive beryllium  
allergy, of which 5 showed an allergic contact stomatitis, probably 
caused by beryllium-containing dental prostheses or cement.  Other 
metals proved negative, except for one case of a positive reaction 
to cobalt. 

9.2  Occupational exposure

9.2.1  Effects of short- and long-term exposures

    The  earliest  reports  describing  a  disease  in  beryllium  
workers appeared in Europe in the 1930s and early 1940s (Weber & 
Engelhardt, 1933; Marradi-Fabroni, 1935; Gelman, 1936; Gelman, 
1938; Menesini, 1938; Berkovitz & Israel, 1940; Meyer, 1942; Wurm & 
Ruger, 1942).  The clinical symptoms resembled metal fume fever, 
chemical pneumonitis, and related pulmonary irritations associated 
with irritant gases, such as phosgene or chlorine, and corrosive 
acids and  alkalis .  Hence,  the  symptoms,  which  are  now  
generally accepted as being typical for the acute disease caused by 
beryllium, were erroneously related to the anions in the beryllium 
compounds, i.e., fluorides and oxyfluorides.  Subsequently, Kress & 
Crispell (1944) and Van Ordstrand et al. (1945) reported the toxic 
potential of beryllium itself, and Hardy & Tabershaw (1946) found 
evidence for a chronic beryllium disease. 

    Following these and other reports, it was soon  generally 
accepted that 2 principal types of disease could be produced by the 
biological action of beryllium after inhalation and/or dermal 
exposure, namely acute and chronic beryllium disease.  The main 
differences between these 2 types are summarized in Table 15.  In 
contrast to many other xenobiotics, the duration of exposure does 
not necessarily govern the type of disease, since low-level 
exposure of a few hours has been reported to produce a chronic 
beryllium disease similar to that following years of exposure.  
Similarly, brief but massive, or prolonged but less intensive, 
exposure to beryllium may cause the acute disease. 

Table 15.  Classification of beryllium-induced non-neoplastic diseasesa
Specification   Type of    Manifestation   Duration   Clinical form     Degree   Outcome, remote 
of beryllium    exposure   of disease                                   or       effects and 
                                                                        stages   complications
Soluble         acuteb     Rapid (within   < 1 year   Acute beryllium   light,   Pneumoclerosis; 
                           3 days)                    disease:          medium,  chronic bronchitis,
                                                      nasopharyngitis,  severe   bronchiectasia;
                short-     Delayed for                tracheobronchitis,         emphysema; 
                termc      several weeks              bronchiolitis,             bronchial asthma;
                                                      pneumonitis,               pulmonary 
                                                      conjunctivitis,            insufficiency;
                                                      dermatosis                 pulmonary heart;
                                                                                 recovery possible
                                                                                 if not fatal

Poorly soluble  long-      Latent period   > 1 year   Chronic           I        Emphysema; 
and             term       of a few weeks             beryllium disease:         spontaneous 
non-soluble                to > 20 years              predominantly              pneumothorax
                           after exposure             interstitial      II       Pulmonary
                           of a few hours             granulomas in              insufficiency
                           to several                 the lungs,        III      Pulmonary heartd;
                           years                      progressive in             cardiovascular
                                                      severity                   insufficiency

Soluble,        long-      Latent period   > 1 year   Chronic toxic     I        Emphysema
poorly soluble  term       of a few weeks             bronchitis;       II       Chronic bronchitis;
and non-soluble            to > 20 years              chronic                    bronchiectasia
                           after exposure             beryllium disease III      Pulmonary
                           of a few hours                                        insufficiency;
                           to several                                            pulmonary heart;
                           years                                                 cardiovascular
a  Adapted from: Burnazian (1983); modified and supplemented.
b  Brief, but massive exposure.
c  Less intensive but prolonged exposure resulting also in acute beryllium disease.
d  Cor pulmonale (right-sided heart failure).  Acute disease

    Tepper et al. (1961) defined acute beryllium disease as follows: 
"to include those beryllium-induced disease patterns with less than 
one year's natural duration and to exclude those syndromes lasting 
more than one year". 

(a)   Skin effects

    Depending on individual susceptibility, direct contact with 
soluble beryllium compounds may cause contact dermatitis 
characterized by reddened, elevated, or fluid-filled lesions on 
exposed surfaces of  the  body.   This  has  not been seen  in  
workers  handling  beryllium hydroxide, pure beryllium, and vacuum-
cast beryllium metal (McCord, 1951; NIOSH, 1972).  The symptoms 
develop after a latent period of 1 - 2 weeks indicating a delayed 
allergic reaction, and a concomitant conjunctivitis may occur.  
After cessation of exposure, the skin eruptions usually disappear, 
whereas, on continued exposure, bronchitis and pneumonitis may 
develop.  Sensitized individuals react much more rapidly and to 
smaller amounts of beryllium (Van Ordstrand et al., 1945). 

    A patch test developed by Curtis (1951) appeared to be 
sensitizing.  Eight out of 16 individuals, without previous 
exposure, developed eczemas from the test itself; also pulmonary 
exacerbations of beryllium disease were related to this test.  Thus, 
it has not been much used for diagnostic purposes (Curtis, 1959; 
Reeves, 1986). 

    When soluble or insoluble beryllium compounds, in crystallized 
form, are introduced into, or beneath, the skin, e.g., as a result 
of abrasions or cuts, chronic ulcerations develop, with granulomas 
appearing, often after several years (Van Ordstrand et al., 1945; 
Lederer & Savage, 1954).  Epstein (1967) classified this reaction as 
granulomatous hypersensitivity.  The granulomas are usually 
painless.  After removal of the beryllium crystals or excision of 
the granulomatous mass, recovery usually takes place within 2 weeks 
(NIOSH, 1972). 

(b)   Respiratory effects

    Acute respiratory effects produced by beryllium were first 
reported in beryllium-extraction plants in the Federal Republic of 
Germany, Italy, the USA, and the USSR.  Several cases occurred as a 
result of the inhalation of soluble beryllium salts, typically the 
fluoride, at concentrations usually greater than 100 µg Be/m3. 

    At a symposium held in 1947 at Saranac Lake, New York (Vorwald, 
1950), about 500 cases of acute beryllium disease, with about one 
dozen deaths, were reported (Eisenbud, 1982).  As a consequence, 
field studies were carried out in the USA, and it soon became 
evident that the acute respiratory effects could be caused by 
inhalation of beryllium fluoride, sulfate, chloride, oxide, or 
hydroxide, and metallic dust (Eisenbud et al., 1948).  The physical 

and chemical properties of the compounds determine the toxicity of 
the associated beryllium ion.  In contrast to low-fired beryllium 
oxide, no cases of acute beryllium disease were observed in workers 
exposed to high-fired beryllium oxide (1540 °C). 

    Eisenbud et al. (1948) reported that all their cases were 
related to beryllium fluoride and sulfate, the most toxic beryllium 
compounds, and were associated with concentrations exceeding 100 µg 
Be/m3.   Concentrations of 1 mg/m3 consistently produced acute 
symptoms among almost all exposed workers.  A group of 8 workers 
exposed to beryllium sulfate at concentrations of not more than 15 
µg Be/m3 (analysed spectrographically) did not develop acute 
disease.  These observations served as a basis for a maximum 
recommended peak value of 25 µg Be/m3. 

    Since the adoption of this value by the Atomic Energy Commission 
and the American Industrial Hygiene Association in the early 1950s 
(section 5.3.2), cases of acute beryllium disease have dramatically 
decreased in the USA.  The US Beryllium Case Registry (a central 
file on reported cases of acute and chronic beryllium disease, which 
was established in 1952) included 224 cases of acute disease, 
registered up to 1983 (Eisenbud & Lisson, 1983).  Most of these 
cases occurred prior to 1949 and were associated with high 
mortality.  Between 1950 and 1967 only 15 non-fatal cases were 
reported, all from beryllium production plants.  An 18-year-old man 
developed acute respiratory disease a few days after exposure to the 
grinding of dies containing a copper-beryllium alloy (Hooper, 1981). 

    The signs and symptoms of acute beryllium disease range from a 
mild inflammation of the nasal mucous membranes and pharynx, i.e., 
rhinitis and pharyngitis, to tracheobronchitis and, depending on the 
degree, duration, and type of exposure, to severe chemical 
pneumonitis (NIOSH, 1972; Constantinidis, 1978). 

    Symptoms of acute pneumonitis, such as progressive cough, 
shortness of breath, substernal discomfort or pain, appetite and 
weight loss, general weakness and tiredness, cyanosis, and 
crepitation, usually occur within 3 days following a massive short-
term exposure or within weeks following prolonged exposure to lower 
concentrations of beryllium. 

    Chest radiographs show diffused haziness of both lungs, 
development of soft irregular infiltration areas with prominent 
peri-bronchial markings, and the appearance of discrete, large or 
small nodules, similar to those found in chronic beryllium disease 
or sarcoidosis (NIOSH, 1972).  Pathological studies on tissue 
samples from 6 patients revealed nongranulomatous acute or subacute 
pulmonary oedema. 

    In severe cases, patients died of acute pneumonitis, but in most 
cases, after cessation of exposure, complete recovery occurred 
within 1-4 weeks.  On re-exposure to beryllium, pneumonitis may 
appear again (Constantinidis, 1978).  In a few cases, chronic 
beryllium disease developed years after recovery from the acute form 
(Hardy, 1965).  Chronic disease

    Chronic beryllium disease differs from the acute form (Table 15) 
in having a latent period that can vary from several weeks to more 
than 20 years.  It is of long duration, progressive in severity, and 
with manifestations that have frequently been described as 
"systemic" (Tepper et al., 1961).  However, often, the systemic 
nature of beryllium disease has been overemphasized, creating the 
impression that inhalation exposure to beryllium caused whole body 
poisoning involving all organs of the body.  In reality, the 
manifestations of chronic beryllium disease are entirely consistent 
with an allergic inflammation of pulmonary tissue in which all 
effects involving other parts of the body are secondary.  Recent 
evidence (Reeves & Preuss, in press) indicates that chronic 
beryllium disease may represent a case of "compartmentalized" immune 
response involving only the alveoli, and resembles other types of 
hypersensitivity pneumonitis. 

    Hardy & Tabershaw (1946) were the first to relate the chronic 
lung disease observed in 17 workers in a fluorescent lamp plant to 
the inhalation of beryllium. In most of these cases, symptoms, such 
as dyspnoea on exertion, cough, and weight loss, appeared several 
months, or even years, after the last exposure.  

    The disease was first called "delayed chemical pneumonitis" 
(Hardy & Tabershaw, 1946).   After the role of beryllium as 
causative agent had been confirmed, the term "berylliosis" became 
widely used.  However, this term is considered misleading by some 
authors (Tepper et al., 1961), first, because it gives the false 
indication that the beryl ore is involved, and second, because this 
disease differs from a typical pneumoconiosis owing to its systemic 
features.  The term chronic beryllium disease is therefore 

    Of the 888 cases registered in the US Beryllium Case Registry 
(section, 224 cases were classified as acute, 42 cases were 
unaccounted for, and 622 cases were classified as chronic, 557 of 
these being due to occupational exposure (Eisenbud & Lisson, 1983).  
The majority of these were either from exposures within the 
fluorescent lamp industry (319 cases) or within beryllium extraction 
plants (101 cases). 

    As with acute beryllium disease, cases of the chronic form 
dramatically declined among workers who had started work in the 
beryllium industry after the implementation of preventive measures, 
but chronic beryllium disease still occurs.  In the Ohio production 
plant, the incidence rate was reduced from 27 cases per 3000 (1940 - 
60) to 2 per 3000 (1960 - 83) in newly hired employees.  These last 
2 cases were attributed to accidentally high exposures (Preuss, 

    The United Kingdom Case Registry 1945-85 numbered 49 cases of 
chronic and 2 cases of acute beryllium disease; 21 beryllium workers 
had died by 1985, most of them from respiratory failure, 3 - 29 
years after diagnosis (Jones Williams, 1985).  In 1988, the United 

Kingdom Registry consisted of 60 cases, indicating that new cases 
were still occurring (Jones Williams, 1988).  Four cases of chronic 
disease developed from acute beryllium disease. 

    In another British study (Cotes et al., 1983), 8 cases of 
chronic beryllium disease were recorded in 1963 (6 cases) and 1977 
(2 cases).  According to air analyses conducted between 1952, the 
first year of operation, and 1960, beryllium concentrations were 
thought to be generally far below 2 µg/m3.  However, the occurrence 
of higher work-place levels cannot be excluded, and this is 
supported by the observation of 2 cases of acute beryllium 

    In Japan, 7 cases of chronic beryllium disease occurred between 
1973 and 1975 (Izumi et al., 1976).  All were related to exposure to 
beryllium oxide in a ceramic factory. 

    Cullen et al. (1987) reported the results of a clinical-
epidemiological investigation concerning work-places and  employees 
of a precious metal refinery in Connecticut, USA, engaged in 
refining and reclaiming beryllium-containing waste materials.  In 
1983, time-weighted average personal air samples, showed a mean 
value of 1.2 µg Be/m3, with a range of 0.22 - 42.3 µg/m3.  Beryllium 
concentrations for furnace tenders, sweepers, and dry pan operators 
were uniformly below 2 µg/m3, while those for samplers, ball mill 
operators, and crushers often exceeded this value.  Thus, it is 
surprising that 4 workers, who had worked in the furnace area 
between 1964 and 1977, developed chronic beryllium disease 4 - 8 
years after the onset of employment.  In the higher exposure areas, 
only one worker developed chronic beryllium disease, diagnosed in 
1985.  These data suggest that the fume from high temperature 
operations is more pathogenic than metal dust and that workers who 
smelt, burn, refine, or weld beryllium or its alloys may still be at 
risk from chronic beryllium disease, even if exposure concentrations 
are below the present adopted standards.  However, it cannot be 
completely ruled out that beryllium concentrations were much higher 
during the period of exposure (1964 - 77) than those measured in 
1983, even though this seems unlikely, because virtually no 
structural changes or changes in work practices had occurred over 
the 20-year period. 

    Infante et al. (1980) also reported a case of chronic beryllium 
disease diagnosed in an individual who had been exposed to extremely 
low levels of beryllium (less than 2 µg/m3) at a rolling mill plant.  
He was initially exposed in 1965 and was diagnosed in 1972. 

    Kreiss et al. (1989) conducted a survey on 58 machinists who 
were exposed to beryllium levels near the current standard.  The 
authors administered a questionnaire, reviewed current medical X-
rays, and conducted pulmonary function tests and a peripheral blood 
lymphocyte transformation test (LTT) on 51 volunteers.  Six had 
abnormal LTT results, and 5 out of 6 sensitized workers agreed to 
clinical and diagnostic evaluation.  Four of the 5 sensitized 
workers, who were evaluated further, had beryllium disease, defined 
as granulomata on trans-bronchial lung biopsy, and a 3-fold or 

higher stimulation index by lung lymphocytes to beryllium salts.  
The 4 cases of beryllium disease were identified among a group of 20 
machinists, first employed 10 or more years prior to the study. 

    Rossman et al. (1988) evaluated the sensitivity and specificity 
of the LTT in relation to the diagnosis of chronic beryllium 
disease.  They reported the results of the LTT on cells derived from 
bronchoalveolar lavage and cells derived from peripheral blood among 
normal individuals, and individuals who had unequivocal beryllium 
disease, probable beryllium disease, or sarcoidosis.  A stimulation 
index of more than 5 times control values was considered a positive 
response with regard to results with cells derived from 
bronchoalveolar lavage; 14 out of 14 patients with unequivocal 
beryllium disease had a positive LTT and 3 individuals with probable 
chronic beryllium disease had a positive LTT.  The LTT was negative 
in 6 beryllium workers who did not have beryllium disease, and also 
negative in 6 normal volunteers and in 16 patients diagnosed as 
having sarcoidosis with no history of exposure to beryllium.  These 
results suggest a high degree of sensitivity and specificity for the 
LTT based on bronchoalveolar lavage. 

    When cells were derived from peripheral blood, 6 of the 14 
patients (42%) with unequivocal chronic beryllium disease had a 
positive LTT.  The peripheral blood LTT was negative for all the 
remaining patients in the study (personal communication, M.D. 
Rossman).  The LTT results based on peripheral blood cells suggest 
that only about half of those with chronic beryllium disease may be 
identified through tests based on lymphocytes derived from blood.  
These findings taken together with those of Kreiss et al. (1989), 
who performed LTTs using peripheral blood, also suggest that the 
chronic beryllium sensitivity in older workers may be more than the 
20% observed in the latter study. 

    In the series of patients studied by Rossman et al. (1988), 
there was a beryllium worker, in addition to those mentioned above, 
who had a history of accidental high exposure and showed typical 
non-caseating lung granulomas on transbronchial biopsy, but no 
clinically manifest disease, according to physiological and 
radiological evaluation.  His lymphocyte blast transformation was 
positive.  This case may represent a subclinical stage of chronic 
beryllium disease leading eventually to manifest illness. 

    The latter finding was confirmed by Newman et al. (1989) who 
studied 8 workers in an aerospace applications plant and 4 workers
in a ceramics manufacturing plant.  Radiographic and physiological
measurements did not reveal evidence of impairment but showed
histopathological pulmonary changes and immunological alterations
(bronchoalveolar lavage LTT positive) consistent with chronic
beryllium disease.  Thus, these cases were considered as "subchronic
beryllium disease".  In addition, 2 out of 8 beryllium workers in 
another group with non-beryllium lung disease showed positive LTT
and were therefore considered to be "beryllium sensitized".

(a)   Signs and symptoms

    The most common signs and symptoms of the chronic disease are 
shown in Tables 16 and 17.  Pneumonitis associated with dyspnoea on 
exertion, cough, chest pain, weight loss, fatigue, and general 
weakness is the most familiar and striking feature (Hardy, 1948; 
Hardy & Stoeckle, 1959).  Right heart enlargement (cor pulmonale) 
with accompanying cardiac failure, hepatomegaly, splenomegaly, 
cyanosis, and finger clubbing may also occur (Hall et al., 1959).  
The appearance of renal stones is quite common, associated with 
renal colic and dysuria.  In spite of the high blood uric acid 
levels, gout does not occur frequently (Kelley et al., 1969).  
Stoeckle et al. (1969) found cases of osteosclerosis associated with 
chronic beryllium disease.  Changes in serum proteins and liver 
function have also been observed. 

Table 16.  Signs of chronic beryllium diseasea
Sign                         Frequency (%)
Chest signs                  43
Cyanosis                     42
Clubbing                     31
Hepatomegaly                 5
Splenomegaly                 3
   cardiac failure           17
   renal stone               10
   pneumothorax              12
a  Adapted from: Hall et al. (1959).

Table 17.  Symptoms of chronic beryllium diseasea
Sign                         Frequency (%)
   on exertion               69
   at rest                   17

Weight loss
   more than 10%             46
   0-10%                     15

   nonproductive             45
   productive                33

Fatigue                      34
Chest pain                   31
Anorexia                     26
Weakness                     17
a  Adapted from: Hall et al. (1959).

    Andrews et al. (1969) conducted lung function tests on 35 
patients.  Only 2 cases had normal test results;  11 patients had an 
interstitial defect, 16 a restrictive defect, and 5 showed evidence 
of airway obstruction. 

    Kriebel et al. (1988) studied the sub-clinical effects of 
beryllium on lung  function  in  beryllium  plant  workers.   After  
the  data  were adjusted for age,  height,  and smoking,  decrements 
in forced vital capacity and forced expiratory volume (in one 
second) were observed in workers exposed to beryllium for more than 
20 years prior to the health survey.  These decrements were observed 
in workers who had no radiographic abnormalities. 
    Studies of pathological changes in numerous cases of chronic 
beryllium disease have been reported by Dutra (1948), MacMahon & 
Olken (1950), Jones Williams (1958), Dudley (1959), Freiman (1959), 
and Freiman & Hardy (1970).  Macroscopically, the lungs may show 
diffuse changes, affecting all lobes with widespread scattered small 
nodules and interstitial fibrosis.  Epithelioid (sarcoid-like) 
granulomas are the characteristic feature, together with conspicuous 
alveolitis.  The early granulomatous lesions are aggregates of 
epithelioid cells surrounded by a poorly defined collection of 
lymphocytes and plasma cells.  Later Langhan-type giant cells 
develop from the fusion of epithelioid cells.  Occasionally, the 
granulomas fuse to form dense hyalinized nodules. 

    On light microscopy (Jones Williams, 1958),  histochemistry 
(Williams et al., 1969), and electron-microscopy (Jones Williams et 
al., 1972), the epithelioid cells, characteristic of the granulomas, 
were indistinguishable from those in sarcoidosis, Kveim test 
granulomas, tuberculosis, farmer's lung, and Crohns disease.  The 
same holds true for the appearance of conchoidal (Schaumann) bodies, 
crystals, and asteroid bodies, which are often numerous in the 
fibrotic stage of beryllium-induced granulomas. 

    Dudley (1959) stressed the importance of the diffuse 
interstitial infiltration of which the granulomas are only a part.  
It was claimed by Freiman & Hardy (1970) that extensive interstitial 
change forecast a more severe disease and that it would be a 
valuable criterion in distinguishing chronic beryllium disease from 
the very similar granulomatous disease, sarcoidosis. 

    Skin lesions, resembling those of sarcoidosis, may be present as 
a secondary response (Tepper et al., 1961).  In addition, granulomas 
may develop in different parts of the body.  Högberg & Rajs (1980) 
found granulomatous myocarditis as the cause of death in two 
beryllium workers. 

    Jones Williams & Kilpatrick (1974) reported one case in which 
local implantation of beryllium led to the generalized disease.  A 
beryllium worker originally had an injury to his hand contaminated 
with beryllium oxide.  A chronic ulcer developed and the affected 
finger had to be amputated.  After several months, ulcerative 
nodules  developed on the forearm and later the lungs were also 
affected.  The patient suffered from dyspnoea.  Electron microscopic 

examination revealed granulomas in the arm and lung lesions, which 
disappeared after treatment with corticosteroids.  However, 
inhalation exposure to beryllium, due to failures in the exhaust 
ventilation, cannot be excluded. 

    Jones Williams et al. (1988) reported skin lesions in 26 
beryllium workers in the United Kingdom.  Fourteen cases were 
diagnosed as chronic beryllium disease.  Of these, 8 had skin 
lesions only, and 6 had both skin and lung disease. 

    The evolution of chronic beryllium disease is not 
uniform.  In some cases, spontaneous alleviation for weeks or years 
is encountered, followed by exacerbations.  In the majority of 
cases, progressive pulmonary disease occurs with an increased risk 
of death from cardiac or respiratory failure.  The reported 
morbidity rates among the beryllium workers vary from 0.3 to 7.5%.  
The length of the latent period and the severity of chronic 
beryllium disease are in reverse proportion.  Bencko & Vasilyeva 
(1983) reported that latent periods of less than 1 year resulted in 
fatality rates as high as 37%, while in patients with a latent 
period of 5 - 10 years, the mortality rate was only 18%. 

(b)   Mechanism of chronic beryllium disease 

    The absence of dose-response relationships and the observation 
that very low inhalation exposure may provoke chronic beryllium 
disease in sensitized subjects suggest that an immunological 
mechanism is involved.  In 1951, Sterner & Eisenbud (1951) developed 
a concept for the pathogenesis of beryllium disease based on the 
hypothesis that "the essential mechanism is a modified immunological 
reaction".  At the same time, Curtis (1951) developed a patch test 
that gave a positive response in many cases of beryllium disease  
(Curtis, 1959) and in beryllium-exposed workers (Nishimura, 1966). 

    Resnick et al. (1970) found an increased concentration of the 
immunoglobulin fraction IgG in subjects who had had either the 
cutaneous or the chronic pulmonary forms of beryllium disease.  
Increased concentrations of IgG, IgA, and IgM were observed by 
Bencko et al. (1980) in workers in 2 Czechoslovakian power plants 
(section 9.1), who were exposed to up to 8 µg Be/m3.  However, 
because of confounding factors, these findings cannot be regarded 
unequivocally as a specific humoral antiberyllium reaction. 

    In several studies, an antibody has not been found in the serum 
of patients with beryllium disease (Voisin et al., 1964; Pugliese et 
al., 1968; Resnick et al., 1970).  However, there is increasing 
evidence that the delayed cutaneous and granulomatous hypersensivity 
are cell-mediated (section 8.7.2).  This is supported, not only by 
the cutaneous sensitivity reaction, but also by lymphoblast 
transformation, and the production of a migration inhibitory factor 
by lymphocytes (Reeves & Preuss, 1985).  It is also supported by the 
skin sensitivity in guinea-pigs that is transferred by lymphocytes, 
but not by serum (Alekseeva, 1966; section 8.7.2). 

    The guinea-pig could serve as a model to explain the "negative" 
dose-response relationship in man.  Workers with relatively high 

exposure over several years sometimes developed immunity, whereas 
with very short work-place exposure and in the "neighbourhood 
cases", only marginal exposure led to chronic beryllium disease 
(Reeves & Preuss, 1985). 

    Reeves & Preuss (1985) suggested that the reactive species is 
always solid-state and is the oxide with a high density of surface 
electrostatic charges.  Particles of beryllium metal become active 
through surface oxidation; ionic beryllium, once entered into 
buffered tissue, precipitates to beryllium hydroxide, which, in 
turn, ages to form the oxide.  Reeves & Preuss (1985) also suggested 
that it is an adsorptive beryllium-protein complex rather than an 
ion-bond proteinate that acts as the proximate antigen. 

    The considerable variability in latency and the lack of dose-
response relationships may be explained by immunological 
sensitization.  Acute infection, surgery, pregnancy, or other 
conditions have often been observed to precede the onset of clinical 
symptoms of beryllium disease (Hardy, 1965; 1980; Clary et al., 
1972).  In particular, pregnancy seems to be a precipitating 
condition; 66% of 95 females registered among the fatal cases in the 
US Beryllium Case Registry were pregnant (Hardy, 1965). 


(c)   Diagnosis

    Drury et al. (1978) and Reeves (1986) have summarized the 
diagnostic criteria.  Since some kind of exposure to beryllium must 
have preceded the disease, the establishment of exposure by history 
taking and tissue analysis should serve as a basis for the 
recognition of chronic beryllium disease, though the presence of 
beryllium in biological material does not prove disease. 

    Clinical criteria that indicate beryllium disease include 
scattered opacities on chest X rays, impaired lung function, 
interstitial pneumonitis, and systemic toxicity.  However, other 
types of interstitial lung disease show similar pathophysiological 

and radiological features.  Differentiation between chronic 
beryllium disease and sarcoidosis is most difficult. 

    The patch test developed by Curtis (1951) is not recommended for 
the diagnosis of beryllium disease, because it can give false 
positives and negatives.  Moreover, it may itself induce a skin 
sensitivity reaction or flare-ups in dormant pulmonary lesions. 

    The macrophage migration inhibition assay and the lymphoblast 
transformation test are useful indicators of beryllium 
hypersensitivity (Reeves & Preuss, 1985).  Both  in vitro tests are 
gaining importance as useful methods for the diagnosis of beryllium 
disease.  Using the lymphocyte transformation test, Deodhar et al. 
(1973) and Preuss et al. (1980) reported positive results in about 
70% of beryllium disease patients.  Jones Williams & Williams (1983) 
found a 100% positive response in 16 patients with chronic beryllium 
disease, and a negative response in 10 subjects who were suspected 
of having chronic beryllium disease.  Only 2 out of 117 healthy 
beryllium workers had a positive response. 

    The lymphocyte transformation test was also 100% positive, 
independent of steroid therapy, and reproducible in 7 patients 
(Williams & Jones Williams, 1982).  In contrast, the macrophage 
migration inhibition test was only positive in 4 patients (57%) who 
were not on steroids, and was not reproducible. 

    Bargon et al. (1986) suggested that lymphocyte transformation 
test results should only be considered as evidence of beryllium 
disease if there were positive test results over a wide range of 
concentrations.  Of 23 foundry workers, 3 showed clear positive 
results.  Two of these workers were diagnosed as having diffuse 
granulomatous lung disease;  the other worker did not show any signs 
of an interstitial lung disease.  In the other exposed workers and 
20 non-exposed controls, lymphocyte transformation test results were 
either negative or only positive at one or two concentrations. 

    Rossman et al. (1988) have reported the development of a fairly 
reliable test for chronic beryllium disease.  The test measures the 
proliferative response of bronchoalveolar lymphocytes to beryllium.  
In 14 patients diagnosed with chronic beryllium disease, the 
bronchoalveolar lymphocytes showed a positive dose-related 
proliferative response to beryllium sulfate.  This response was not 
observed in 6 normal volunteers, 16 patients with sarcoidosis, or 4 
beryllium workers proved not to have chronic beryllium disease. 

    Rossman et al. (1988), Newman et al. (1989), and Saltini et al. 
(1989), confirmed that the lymphocyte transformation test is 
generally more sensitive and specific using lymphocytes from 
bronchoalveolar lavage than using peripheral blood lymphocytes. 

    Based on the findings of beryllium-related pathological and 
immunological alterations in the absence of radiographic or 
physiological impairment, Newman et al. (1989) suggested the 
following classification: 

- Beryllium-sensitization:  persons with a positive blood and/or 
  lung lymphocyte transformation test; 

- Subclinical beryllium disease:  persons with additional 
  pathological alterations on biopsy, but who are asymptomatic; 

- Clinical beryllium disease:  persons who meet all the diagnostic 
  criteria and have clinical symptoms or measurable impairment. 

    The lymphocyte transformation test, especially if performed on 
bronchoalveolar lavage, appears to be the method of choice for the 
detection of beryllium hypersensitivity.  Workers with positive 
results should be considered for removal from further exposure (see 
section 11). 

9.3  Carcinogenicity

9.3.1  Epidemiological studies

    Hardy et al. (1967) reviewed the mortality and morbidity data of 
the US Beryllium Case Registry for the period 1952 - 66.  They did 
not find any evidence that beryllium caused cancer in human beings.  
Likewise, Stoeckle et al. (1969) reviewing the clinical findings and 
course in 60 patients with chronic beryllium disease noted 17 
deaths, but none due to cancer.  Mancuso & El-Attar (1969) 
introduced an epidemiological approach in the study of the mortality 
pattern of beryllium workers at 2 separate companies.  The study was 
based on the social security files of 3685 white males employed from 
1937 to 1948.  From 729 deaths up to the year 1966, 31 were due to 
lung cancer.  Because of several principal limitations, particularly 
the small numbers in the 160 subcategories into which the 729 deaths 
were distributed, it was not possible to make any trend statements 
or statistical tests, leaving open the question of carcinogenic 

    In the study by Mancuso (1970), a subgroup of individuals at the 
Ohio plant, who had clinical case histories of beryllium-induced 
acute  bronchitis  or  pneumonitis,  had  been  identified  between 
1940 - 48 and were followed-up until 1967.  A higher rate of lung 
cancer was noted among the 145 workers previously diagnosed with 
acute bronchitis or pneumonitis compared with the rate among those 
without acute illness.  Six out of 8 (75%) of the lung cancer cases 
identified in the Ohio cohort up to 1967 came from the group of 145 
workers diagnosed with acute pneumonitis, which represented less 
than 15% of the cohort. 

    Bayliss et al. (1971) studied workers in the beryllium-
processing industry in Ohio and Pennsylvania.  They observed a 
slightly elevated risk of lung cancer, though the results were not 
statistically significant. 

    Between 1979 and 1980, reports of these cohorts were updated by 
Mancuso (1979; 1980) and by Wagoner et al. (1980).  A formal 
epidemiological study of individuals entered in the US Beryllium 
Case Registry (BCR) was reported by Infante et al. (1980).  These  
investigations serve as the basis for the analysis of the mortality 
patterns of workers exposed to beryllium. 

    Criticisms  have  been  raised  (US EPA,  1987)  about  the  
interpretation of the excess lung cancer risk observed in the 
studies by Mancuso (1979; 1980), Wagoner et al. (1980), and Infante 
et al. (1980).  The major concerns relate to selection bias, 
confounding from cigarette smoking, and underestimation of the 
expected number of lung cancer deaths reported in the original 
studies.  These issues will be dealt with in the following review.  
In particular, it should be noted that the data presented here are 
based on the ratios of observed versus expected deaths, as 
recalculated by Saracci (1985), taking into consideration the 
increased incidence of lung cancer between 1968 and 1975 in the 
total US population. 

    Mancuso (1979) studied all white males employed at some time 
between 1 January 1942 and 31 December 1948 at the Ohio and 
Pennsylvania facilities.  Cohort members were identified by payroll 
records submitted quarterly by the employer to the US Social 
Security Administration.  These cohorts were followed up to 1974 for 
Ohio and up to 1975 for Pennsylvania.  Observed deaths from lung 
cancer were compared with the number of deaths using United States 
national mortality rates adjusted for age and calendar time periods.  
However, rates for 1965 - 67 were also used to estimate expected 
mortality for the years 1968 - 75.  This procedure resulted in an 
underestimation of expected lung cancer mortality by about 10% 
(Saracci, 1985).  Thus, the expected mortality from lung cancer 
reported in Mancuso (1979) has been increased by 10%.  The observed 
(O) deaths from lung cancer together with the "adjusted" expected 
(E) number of lung cancer deaths for the Ohio and Pennsylvania 
facilities are shown in Table 18.  Among the Ohio workers, the 
overall risk ratio of lung cancer was 1.8 (95% confidence interval 
(CI) is 1.2 - 2.7).  (When the lower number of the CI is 1.0 or 
more, the risk ratio is significantly elevated).  The significantly 
elevated overall risk of lung cancer is confined to individuals who 
were employed for less than one year and 1 - 4 years and were 
followed for more than 15 years from initial employment.  For those 
followed for more than 15 years, the risk ratio is 2.0 (95% CI = 1.3 
- 3.1). 

    As shown in Table 18, the cohort of Pennsylvania employees had 
an overall risk of 1.2 (95% CI = 0.9-1.7).  However, for individuals 
followed  for  more  than  15  years,  the  risk  ratio  was  1.5  
(95% CI =1.0 - 2.1).  Consistent with the observations from the Ohio 
employees, the Pennsylvania beryllium workers' elevated risk of lung 
cancer was confined to individuals, employed for less than one year 
or for 1 - 4 years, who had been followed for 15 or more years since 
initial employment. 

Table 18.  Observed (O) and expected (E) deaths due to lung cancer and their ratios with 95% confidence interval (CI) 
according to duration of employment and time since onset of employment in two US beryllium production facilites at some time 
between 1 January 1942 and 31 December 1948, followed through 31 December 1974a
Interval                        Duration of employment (years)
since                   <1                            1-4                        >5                           Total
onset of     --------------------------   ---------------------------   ------------------------   --------------------------
employment   O/E        Ratio   CI        O/E         Ratio   CI        O/E      Ratio   CI        O/E        Ratio   CI
(i)   Ohio facility
< 15         3/1.96     1.5     0.3-4.5   0/0.70      0       0-5.3     0/0.26   0       0-14.2    3/2.92     1.0     0.2-3.0
> 15         14/7.14    2.0     1.1-3.3   5/1.91      2.6     0.8-6.1   3/1.79   1.7     0.3-4.9   22/10.84   2.0     1.3-3.1
Total        17/9.10    1.9     1.1-3.0   5/2.61      1.9     0.6-4.4   3/2.05   1.5     0.3-4.3   25/13.76   1.8     1.2-2.7

(ii)   Pennsylvania facility
< 15         3/4.70     0.6     0.1-1.9   1/2.11      0.5     0.1-2.6   0/0.98   0       0-4.1     4/7.79     0.5     0.1-1.3
> 15         23/14.12   1.6     1.0-2.4   10.5/5.80   1.7     0.8-3.2   3/4.30   0.7     0.1-2.0   36/24.22   1.5     1.0-2.1
Total        26/18.82   1.4     0.9-2.0   11/7.91     1.4     0.7-2.5   3/5.28   0.6     0.1-1.7   40/32.01   1.2     0.9-1.7
a  Adapted from: Saracii (1985); original study from Mancusco (1979).
    Mancuso (1980) followed both the Ohio and Pennsylvania cohorts 
up to 1976 and pooled the data from both cohorts.  He compared their 
expected lung cancer mortality with that expected on the basis of 
the mortality rates of other industrial workers who were employed in 
the same geographical area and for similar periods of time and were 
followed for a similar calendar time period.  As shown in Table 19, 
the risk ratios for lung cancer were significantly elevated whether 
the expected was based on "all viscose rayon" employees or on those 
who had never transferred from their department of initial 
employment.  The lung cancer risk ratios range from 1.4 to 1.6 and 
are statistically significant.  If the data shown in Table 18 are 
combined, the overall risk of lung cancer is 1.4 with expected 
mortality based on the US general population rates.  Thus, the risk 
range of 1.4 - 1.6 with expected mortality based on the viscose 
rayon employees is similar.  Mancuso (1980) did not present data on 
cigarette smoking among his beryllium cohort members.  However, an 
indirect indication that cigarette smoking may not have played a 
major role in the increased lung cancer risk among beryllium 
employees can be derived from the observation that, when a 
population of industrial workers was used to compute expected 
mortality, the elevated lung cancer risk remained about the same.  
It could be presumed that blue collar workers, employed in the same 
geographical area over the same calendar time period, who had 
similar length of employment patterns, would have similar smoking 
habits.  Thus, it is considered unlikely that cigarette smoking 
played a major role in the excess lung cancer risk. 

    Wagoner et al. (1980) conducted a cohort study on beryllium 
production workers employed at the Pennsylvania facility that was 
studied by Mancuso (1979, 1980).  However, Wagoner et al. (1980) 
identified their cohort members through company records and a 
medical survey conducted at the facility in 1968.  The cohort 
consisted of 3055 white males who were employed for some time during 
the period from January 1942 to September 1968.  The cohort was 
followed through 1975.  Observed mortality was compared to the 
expected, based on the US white male general population, adjusted 
for age and calendar time period.  However, lung cancer rates for 
1965 - 67 were also used to estimate expected mortality for the 
years 1968 - 75.  Therefore, the expected lung cancer mortality, as 
reported in the Wagoner et al. (1980) paper, has been increased by 
10%.  The results for lung cancer are shown in Table 20.  For the 
total group, 47 lung cancer deaths were observed compared with 37.72 
expected.  The risk ratio was 1.2 (95% CI = 0.9 - 1.7).  For those 
followed for 25 or more years since initial employment, the ratio 
was significantly elevated, O/E = 1.7 (95% CI = 1.0 - 2.6).  The 
risk of lung cancer also increased with an increase in latency, but 
not with duration of employment.  NIOSH re-analysed the data using 
updated lung cancer rates (Foege, Personal communication, 1981).  
The results demonstrated a significant increase in lung cancer 
deaths for those with more than 15 years of latency (39 observed 
versus 13.36 expected,  P = 0.035). 

Table 19.  Observed (O) deaths due to lung cancer among 35 to 74-year-
old workers of two US beryllium production facilities as contrasted 
with those expected (E) on the basis of two cohorts of workers in the 
viscose rayon industry employed for similar durations of time and 
followed over the same period of timea
Duration of               Lung cancer mortalityb
employment    ---------------------------------------------------------
(months)      O/Ec        Ratio   CI        O/Ed       Ratio   CI     
< 12          52/37.60    1.4     0.9-2.1   52/31.67   1.6     1.1-2.6
13-48         14/13.26    1.1     0.5-2.2   14/10.82   1.3     0.6-2.9
49            14/6.32     2.2     0.9-5.7   14/8.14    1.7     0.7-4.1

Total         80/57.18    1.4     1.0-2.0   80/50.63   1.6     1.1-2.2
a  Adapted from: Saracci (1985); original study from Mancuso (1980).
b  CI = 95% confidence interval.
c  All viscose rayon employees.
d  Viscose rayon employees who had never transferred from department of
   inital employment.

    Table 20 provides data for mortality from non-malignant lung 
disease (excluding influenza and pneumonia).  Overall, the risk 
ratio was 1.6 (95% CI = 1.1 - 2.3).  The excess appears to be 
restricted to those employed for less than 5 years, O/E = 1.9 (95% 
CI = 1.2 - 2.7).  A significant excess of mortality was seen for 
heart diseases.  There were 396 deaths observed compared with 349.32 
expected.  The risk ratio was 1.1 (95% CI = 1.0-1.2).  A large 
number of these individuals died from right-sided heart failure (cor 
pulmonale) as a consequence of beryllium lung disease.  These data 
are not shown in tabular form. 

    Concern has arisen that this study may have bias in the 
selection of cohort members for study.  However, the results for 
lung cancer in the Wagoner et al. (1980) study of the Pennsylvania 
cohort, as shown in Table 20, are virtually the same as those 
reported in Mancuso's study of the same facility, using records on 
employment derived from the social security administration. 

    With regard to the effect of cigarette smoking on the increased 
lung cancer risk, it has been estimated that difference in smoking 
habits between the cohort members and the general population may 
account for about 4% of the increased risk (Saracci, 1985). 

Table 20.  Observed (O) and expected (E) deaths and their ratios with 95% confidence interval 
(CI) due to (i) lung cancer and (ii) non-neoplastic respiratory disease, according to 
duration of employment and time since onset of employment in a US beryllium production facility 
(Pennsylvania) at some time between January 1942 and September 1968, followed through 1975a
Interval                           Duration of employment (years)b
since        ----------------------------------------------------------------------------------
onset of                < 1                        14                           Total
employment   --------------------------   ------------------------   --------------------------
(years)      O/E        Ratio   CI        O/E      Ratio   CI        O/E        Ratio   CI
(i)   Deaths due to lung cancer
< 15         8/8.74     0.9     0.4-1.8   1/1.63   0.6     0.1-3.8   9/10.37    0.9     0.4-1.6
15-24        16/12.72   1.2     0.7-1.9   3/2.76   1.1     0.2-3.5   18/15.48   1.2     0.7-1.8
> 25         17/9.98    1.7     1.0-2.7   3/1.89   1.6     0.4-5.1   20/11.87   1.7     1.0-2.6
Total        41/31.44   1.3     0.9-1.7   7/6.28   1.1     0.4-2.3   47/37.72   1.2     0.9-1.7

(ii)   Deaths due to non-neoplastic respiratory disease
< 15         6/3.57     1.7     0.6-3.7   1/0.66   1.5     0.1-8.4   7/4.23     1.7     0.7-3.4
15-24        11/6.36    1.7     0.9-3.1   1/1.41   0.7     0.1-4.0   12/7.77    1.6     0.8-2.7
> 25         12/5.62    2.1     1.1-3.7   0/1.15   0       0-3.2     12/6.77    1.8     0.9-3.1
Total        29/15.55   1.9     1.2-2.7   2/3.22   0.6     0.1-2.2   31/18.77   1.6     1.1-2.3
a  Adapted from: Saracci (1985), original study from Wagoner et al. (1980).
b  Employment histories ascertained only for 1967-68.
    Infante et al. (1980) studied a group of 421 white males who had 
been entered with the US Beryllium Case Registry, while alive, 
between 1 July 1952 and 31 December 1975.  The cohort was followed 
through 1975.  The NIOSH modified life-table method was used to 
calculate expected mortality.  Again, because of the problem of 
underestimation of expected lung cancer mortality, the expected 
numbers of deaths have been increased by 10%.  The results for lung 
cancer and for death from non-malignant respiratory disease are 
shown in Table 21.  A significantly elevated risk ratio for lung 
cancer (6 observed versus 2.10 expected, 95% CI = 1.0 - 6.2) was 
observed among those who were entered in the Registry with a 
diagnosis of beryllium-induced acute pneumonitis or bronchitis.  No 
excess of lung cancer was observed among those entered with chronic 
respiratory disease (1 observed death versus 1.52 expected, 95% CI = 
0.7 - 3.7).  However, the overwhelming excess of mortality due to 
non-neoplastic respiratory disease (42 observed deaths, 0.65 
expected, 95% CI = 46.6-87.3) may have limited the ability to detect 
an excess of lung cancer in this latter group.  Another interesting 
observation is that those who were  entered in the Registry with a 
diagnosis of acute respiratory illness had a 10-fold increased risk 
of dying from chronic non-neoplastic respiratory disease.  The risk 
ratio is 10.3 (95% CI = 4.9-18.9) as shown in Table 21. 

Table 21.  Observed (O) and expected (E) deaths and their ratios with 
95% confidence interval (CI) due to lung cancer and non-neoplastic 
respiratory disease among white males enrolled in the US Beryllium Case 
Registry, while alive, between 1 July 1952 and 31 December 1975a
Interval                Lung cancer       Non-neoplastic respiratory
since                                     disease
beryllium    O/E        Ratio   CI        O/E      Ratio   CI
(i)   Acute respiratory illness group (N = 223)
< 15         1/0.38     2.6     0.1-14.7  1/0.14   7.1     0.2-39.8
> 15         5/1.72     2.9     0.9-6.8   9/0.83   10.8    5.0-20.6
Total        6/2.10     2.9     1.0-6.2   10/0.97  10.3    4.9-18.9

(ii)   Chronic respiratory disease group (N = 198)
< 15         0/0.155    0       0-24.6    9/0.05   180.0   82.3-341.7
> 15         1/1.36     0.7     0.1-4.1   33/0.60  55.0    37.9-77.2
Total        1/1.52     0.7     0.1-3.7   42/0.65  64.4    46.6-87.3
a  Adapted from: Saracci (1985); original study from Infante et al. (1980).
b  Excluded influenza and pneumonia.


10.1  Evaluation of human health risks

    Beryllium is widely distributed in the environment, generally 
occurring in trace quantities.  The growing use of this element in 
high technology applications increases the potential for exposure 
to beryllium in its various forms, particularly beryllium metal, 
beryllium oxide, and beryllium-containing alloys.  Inhalation 
exposure is the most significant route in terms of risk of adverse  
health effects.  Skin contact with beryllium metal and its 
compounds is also of concern. 

    Provided that control measures in the beryllium industry  are 
adequate, general population exposure today is mainly confined to 
low levels of airborne beryllium from the combustion of fossil 
fuels, especially coal.  In more exceptional cases, where the 
beryllium content of the coal being burned is unusually high and no 
adequate control measures are applied, this source could pose 
health problems.  Tobacco smoking probably contributes to 
inhalation exposure but, at present, there are only limited data.  
The use of beryllium for dental protheses must also be taken into 
consideration, in view of its high sensitization potential.  There 
is a small intake from water and food;  from a toxicological point 
of view, the ingestion of beryllium is of minor importance.  
However, the present data base is insufficient for a quantitative 
assessment of beryllium intake via air, food, drinking-water, and 
tobacco smoke. 

    Depending on individual susceptibility, direct contact with 
soluble beryllium salts can cause delayed (contact)  dermatitis, 
occasionally associated with conjunctivitis.  When beryllium 
compounds are retained in, or beneath, the skin, chronic 
granulomatous ulcerations develop. 

    Acute effects on the respiratory tract including 
nasopharyngitis, bronchitis, and severe chemical pneumonitis have 
been reported as an occupational disease among beryllium workers 
exposed to high concentrations of fumes or dust, usually exceeding 
100 µg Be/m3.  In particular, beryllium fluoride and sulfate, but 
also the low-fired oxide, have produced acute poisoning, while the 
less soluble high-fired oxide has not caused acute beryllium 
disease.  Usually, complete recovery has occurred after removal 
from the exposure, but in severe cases, patients have died of 
pneumonitis.  After the implementation of preventive measures, 
cases of acute beryllium disease have drastically decreased and, 
today, may only occur as a consequence of failures in control 

    Inhalation of beryllium can also produce chronic beryllium 
disease, either years after recovery from the acute form or, more 
commonly, independently, after a latent period varying from several 
weeks to more than 20 years and, frequently, several years after 
termination of exposure.  The clinical, radiological, functional, 
and pathological features of chronic beryllium disease resemble 

those of sarcoidosis, though the interstitial inflammatory reaction 
tends to be more prominent in chronic beryllium disease.  
Primarily, the lung is affected.  Pulmonary disease associated with 
dyspnoea on exertion, cough, chest pain, weight loss, and general 
weakness is the most familiar and striking feature.  Effects on 
other organs may be secondary rather than systemic effects.  
Epithelioid granulomas with varying amounts of interstitial 
inflammation form the characteristic microscopic picture.  The 
highest morbidity rates have been found in patients who developed 
the disease after a latency period of less than one year.  No 
correlation has been found between the intensity of exposure and 
the severity of the disease.  The great variability in latency and 
the lack of dose-response relationships in chronic beryllium 
disease may be explained by immunological sensitization.  Pregnancy 
seems to be a precipitating "stress factor".  The adoption of 
exposure standards has clearly decreased the incidence of chronic 
beryllium disease.  However, this disease may still occur among 
sensitized individuals who have been exposed to concentrations of 
around 2 µg/m3. 

    The available data from genotoxicity tests indicate that 
beryllium interacts with DNA and causes gene mutations, chromosomal 
aberrations, and sister chromatid exchange in cultured mammalian 
somatic cells, though it has been found not to be mutagenic in 
bacterial test systems. 

    Intravenous and intrameduallary injection of beryllium metal 
and various compounds produced bone cancer in rabbits, but not in 
guinea-pigs, rats, and mice.  Inhalation or intratracheal exposure 
to soluble and insoluble beryllium compounds, beryllium metal, 
various beryllium alloys, or beryl induced lung tumours in rats.  
No pulmonary tumours have been observed in rabbits, hamsters, or 
guinea-pigs.  On the whole, the carcinogenic activity of beryllium 
in different animals has been confirmed, though study design and 
laboratory practice at the time these studies were conducted were 
mostly not in compliance with the current approaches used in 
carcinogenicity tests.  In particular, the reported exposure data 
should be considered with caution. 

    Several epidemiological studies have provided data indicating 
an excess lung cancer incidence in populations occupationally 
exposed to beryllium.  These data were derived from studies of two 
United States  working  populations and a registry of clinical 
cases  partially covering these same populations as well as other 
occupations.  The question pending is whether chance, bias, or 
confounding, rather than exposure to beryllium, can explain the 
association (Saracci, 1985). 

    The cohorts of beryllium workers employed at both the Ohio and 
Pennsylvania production facilities indicate a statistically 
significant excess risk of lung cancer after long intervals from 
initial exposure (15 - 25 years) among workers with less than 5 
years' duration of employment.  The data base from one of the 
studies  of  the Pennsylvania cohort has been scrutinized closely.  
The fact that two different approaches to cohort selection (use of 

social security data by Mancuso (1979) and the use of company 
records by Wagoner et al. (1980)) result in essentially concordant 
findings is evidence against the  role of major bias in subject 
selection or response assessment.  Another fact against selection 
bias is that the elevated lung cancer risk ratios were similar in 
the Mancuso (1980) study when an industrial reference population, 
selected in a manner similar to the beryllium cohort, was used for 
comparison rather than the United States white male population 
(Saracci, 1985). 

    After chance and bias, confounding from cigarette smoking needs 
to be considered.  The distribution of cigarette smoking was 
determined from a morbidity survey conducted at the Pennsylvania 
facility in 1968 and was reported by Wagoner et al. (1980).  On the 
basis of these data, Saracci (1985) estimated that the difference 
in smoking habits between the beryllium workers and the general 
population was such as to increase the risk of lung cancer by 4% 
over the risk in the general population.  Other evidence against 
smoking playing a major role in the elevated lung cancer risk was 
provided indirectly by Mancuso (1980), who observed a significant 
increase in lung cancer in the beryllium workers compared with an 
industrial population from the same geographical area.  (Smoking 
habits and other socioeconomic factors are assumed to be similar in 
these two groups of blue collar workers).  Thus, the observed 
increase in lung cancer could hardly be accounted for by smoking 

    If the increased risk of lung cancer is partially or totally 
related to beryllium exposure, it would be expected that the 
greater the exposure, the higher the risk.  Subjects entered in the 
Beryllium Case Registry with a diagnosis of beryllium-induced acute 
pneumonitis or bronchitis had often experienced high exposures.  In 
fact, the Registry data indicate a 3-fold increased risk of lung 
cancer for these subjects (Infante et al., 1980).  Mancuso (1970) 
also reported an elevated frequency of lung cancer in a subgroup of 
the Ohio cohort that was identified as having acute beryllium 

    In the cohort studies on production workers, the increased lung 
cancer risk appeared to be localized among workers with less than 5 
years or less than one year of employment.  As exposure in the 
past, particularly before 1950, was substantially higher, length of 
employment would be a distorted indicator of the actual exposure 
accumulated by a worker.  This explanation for the elevated risk in 
these workers appears to be more likely than an alternative one 
that workers with relatively short employment are a selected group 
who experience higher mortality from lung cancer.  This explanation 
is further supported by the observation of an increased risk of 
lung cancer among beryllium workers compared with other industrial 
workers employed for similar periods of time. 

10.2  Evaluation of effects on the environment

    Data on the fate of beryllium in the environment are limited.  
Atmospheric beryllium oxide particles (combustion processes) return 
to earth by wet and dry deposition.  Within the environmental pH 

range, beryllium is absorbed by finely-dispersed sedimentary 
minerals preventing release to ground water.  Therefore, beryllium 
concentrations in surface waters (µg/litre range) and soils (mg/kg 
dry weight range) are usually low and probably do not affect the 

    Little is known about the effects of beryllium on 
microorganisms.  At high pH, beryllium salts have growth-
stimulating effects on algae and on crop plants.  There is evidence 
that beryllium is able to substitute for magnesium in the growth 
process of crop plants, thus reducing their magnesium requirement.  
At or below pH 7, beryllium is toxic for aquatic and terrestrial 
plants, because of its inhibitory effects on enzyme activity and 
the uptake of essential mineral ions.  Most plants take up 
beryllium in small amounts, but very little is translocated within 
the plant. 

    The toxicity of beryllium for aquatic animals increases with 
decreasing water hardness.  In acute toxicity studies on different 
freshwater fish species, LC50 values ranged between 0.15 and 32 mg 

    No data are available on the effects of beryllium on domestic 
or wild terrestrial animals. 

    There is no evidence that beryllium biomagnifies within food 

10.3  Conclusions

    The health hazards of beryllium are almost exclusively confined 
to inhalation exposure and skin contact.  Except for the accidental 
release of beryllium into the environment, the general population is
only exposed to very low levels of airborne beryllium, which do not
pose a health hazard.  Because of the high sensitization  and
allergenic potential of ionic beryllium, the use of beryllium for
dental protheses should be reconsidered. 

10.3.1.  Acute beryllium disease

    Occupational exposure to beryllium poses a health hazard that 
may result in skin lesions and adverse effects on the respiratory 
tract.  Of the latter, acute beryllium disease can be encountered 
after exposure to relatively high concentrations of beryllium in 
fumes and dust (>100 µg/m3).  Because of improved control 
measures, such high concentrations are not expected to occur in 
today's occupational settings. 

10.3.2  Chronic beryllium disease

    Hundreds of cases of chronic beryllium disease have been 
diagnosed in various countries throughout the world.  The vast 
majority of these cases have been the result of previous exposure 
to high concentrations of beryllium in the extraction and smelting 
of beryllium, fluorescent tube production (no longer a source of 
beryllium exposure), and in beryllium metal production. 

    More recently, cases of beryllium disease have been diagnosed 
following low-level exposure (around 2 µg/m3).  The results of 
recent studies suggest that some degree of immunological 
responsiveness to beryllium may be common among workers exposed for 
more than 10 years.  Thus, current occupational exposure standards 
may not exclude the development of chronic beryllium disease in 
beryllium-sensitized individuals. 

10.3.3  Cancer

    Multiple studies on experimental animals have provided 
sufficient evidence that beryllium is carcinogenic.  The available 
epidemiological data lead to the conclusion that beryllium is the 
most likely single explanation for the excess lung cancer observed 
in exposed workers.a

a  Professor A.L. Reeves dissented from this statement.


1.  There is a need for well conducted inhalation toxicity studies 
on experimental animals, focused on the species- and compound-
specifity of beryllium carcinogenicity. 

2.  Mechanistic studies on the immunotoxicity of beryllium are 

3.  Mechanisms of carcinogenesis should be investigated, including 
the molecular mechanisms of beryllium transport and binding in 
cells and cell nuclei. 

4.  Improvement of analytical methods and the application of 
quality control are necessary. 

5.  Reliable data on the beryllium contents of food, drinking-
water, and tobacco originating from different parts of the world, 
are required. 

6.  In the work-place, regular monitoring of air concentrations of 
beryllium should be performed. 

7.  The use of the lymphocyte transformation test (LTT) should be 
considered for identifying sensitized individuals.  These should be 
permanently removed from further exposure to beryllium. 

8.  Human data on bioavailability, tissue levels, and body burden 
are required. 

9.  Selected human subpopulations should be monitored to determine 
beryllium exposure and body burden. 

10.  The contribution of beryllium released from solid rocket 
propellants and in space technology should be established. 

11.  Individuals suspected of having sarcoidosis, employed in any 
occupation, should be evaluated for immunological sensitivity to 
beryllium, because of the possible unknown exposure to beryllium. 

12.  The use of beryllium for dental protheses should be 
reconsidered, because of the high sensitization and allergenic 
potential of ionic beryllium. 


    An International Agency for Research on Cancer Working Group 
(IARC, 1987) evaluated the carcinogenicity of beryllium and 
assigned beryllium and beryllium compounds to Group 2A, concluding 
that they are probably carcinogenic to human beings.  The 
evaluation was reported as follows: 

"A.   Evidence for carcinogenicity to humans (limited) 

    Observations, reviewed elsewhere on beryllium-exposed subjects 
cover two industrial populations and a registry of berylliosis 
cases.  Workers at beryllium extraction, production and fabrication 
facilities in the USA were followed up and their causes of 
mortality compared with those of both the general population and a 
cohort of viscose-rayon workers.  Ratios of observed to expected 
deaths for lung cancer in the two industrial populations (65 
observed) were found to be elevated in both comparisons (1.4 in 
respect of both the general population [95% confidence interval 
(CI), 1.1 - 1.8] and the viscose-rayon workers [1.0 - 2.0]) and 
tended to be concentrated in workers who had been employed for less 
than five years.  Data from the US Beryllium Case Registry, in 
which cases of beryllium-related lung diseases were collected from 
a wide variety of sources (including the two facilities previously 
mentioned), indicate an approximately three-fold (six deaths 
observed, 2.1 expected;  ratio of observed:  expected, 2.9 [95% CI, 
1.0 - 6.2]) increase in mortality from lung cancer among subjects 
who had suffered from acute berylliosis, which usually follows 
heavy exposure to beryllium, but not among those who had had 
chronic berylliosis (one death observed, 1.4 expected;  ratio of 
observed:expected, 0.7;  95% CI, 0.1 - 3.7). 

B.   Evidence for carcinogenicity to animals (sufficient) 

    Beryllium metal, beryllium-aluminium alloy, beryl, ore, 
beryllium chloride, beryllium fluoride, beryllium hydroxide, 
beryllium sulphate (and its tetrahydrate) and beryllium oxide all 
produced lung tumours in rats exposed by inhalation or 
intratracheally.  Single intratracheal instillations or one-hour 
inhalation exposures were effective.  Beryllium oxide and beryllium 
sulphate produced lung tumours in monkeys after intrabronchial 
implantation or inhalation.  Beryllium metal, beryllium carbonate, 
beryllium oxide, beryllium phosphate, beryllium silicate and zinc 
beryllium silicate all produced osteosarcomas in rabbits following 
their intravenous and/or intramedullary administration. 

C.   Other relevant data

    No data were available on the genetic and related effects of 
beryllium and beryllium compounds in humans. 

    All of the available experimental studies considered by the 
Working Group were carried out with water-soluble beryllium salts.  
In one study, beryllium sulphate increased the frequency of 
chromosomal aberrations and sister chromatid exchanges in human 
lymphocytes and in Syrian hamster cells  in vitro;  in another 

study, chromosomal aberrations were not seen in human lymphocytes.  
It caused transformation of cultured rodent cells in several test 
systems.  In one study, beryllium chloride induced mutation in 
cultured Chinese hamster cells.  Beryllium sulphate did not induce 
unscheduled DNA synthesis in rat hepatocytes  in vitro, mitotic 
recombination in yeast or mutation in bacteria.  Beryllium chloride 
was mutagenic to bacteria." 


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1.  Identité, propriétés physiques et chimiques, méthodes d'analyse

    Le béryllium est un métal gris acier, fragile, qui n'existe à 
l'état naturel que sous la forme d'un seul isotope, le 9Be.  Ses 
composés sont bivalents.  C'est un élément unique par certaines de 
ses propriétés.  Ainsi il est le plus léger de tous les corps 
solides et chimiquement stables, avec un point de fusion, une 
chaleur spécifique, une chaleur de fusion, une charge de rupture 
exceptionnellement élevés.  Il possède une excellente conductivité 
électrique et thermique.  Du fait de son faible numéro atomique, le 
béryllium est très perméable aux rayons X.  Parmi ses propriétés 
nucléaires on peut citer la rupture, la diffusion et la réflection 
de neutrons ainsi que l'émission de neutrons par bombardement alpha.  

    Le béryllium partage un certain nombre de propriétés chimiques 
avec l'aluminium, en particulier sa forte affinité pour l'oxygène.  
Par suite, il se forme à la surface du métal et de ses alliages, 
une péllicule très stable d'oxyde de béryllium (BeO), qui leur 
confère une très grande résistance à la corrosion, à l'eau et aux 
acides oxydants à froid.  A l'état pulvérulent, le béryllium brûle 
dans l'oxygène à une température de 4500 °C.  L'oxyde de béryllium 
fritté est très stable et possède les propriétés d'une céramique.  
Les sels dans lesquels il se trouve à l'état cationique 
s'hydrolisent dans l'eau et réagissent pour former des hydroxydes 
insolubles ou des complexes hydratés, aux valeurs du pH comprises 
entre 5 et 8 et des béryllates au-dessus de pH 8.  

    Aux alliages, le béryllium apporte un ensemble de propriétés 
remarquables, en particulier: résistance à la corrosion, module 
élevé d'élasticité, amagnétisme, propriétés antiétincelantes, forte 
conductivité électrique et thermique et meilleure résistance à la 
rupture que l'acier.  

    On utilise diverses méthodes d'analyse pour la recherche et le 
dosage du béryllium dans les différents milieux.  Parmi les 
méthodes anciennes on peut citer la spectroscopie, la fluorimétrie 
et la spectrophotométrie.  Les méthodes de choix sont la 
spectrométrie d'absorption atomique sans flamme ainsi que la 
chromatographie en phase gazeuse; les limites de détection sont de 
0,5 ng/échantillon (absorption atomique sans flamme) et de 0,04 
pg/échantillon (chromatographie en phase gazeuse avec détection par 
capture d'électrons).  En outre, la spectrométrie d'émission 
atomique à plasma avec couplage par induction s'utilise de plus en 

2.  Sources d'exposition humaine et environnementale

    Le béryllium se situe au trente-cinquième rang des éléments par 
ordre d'abondance dans la croûte terrestre avec une teneur moyenne 
d'environ 6 mg/kg.  Exception faite des pierres précieuses, de 
l'émeraude (béryl contenant du chrome) et de l'aigue-marine (béryl 
contenant du fer), il n'existe que deux minéraux qui présentent une 
importance économique.  Le béryl contient jusqu'à 4% de béryllium 
et il est extrait en Argentine, au Brésil, en Chine, en Inde, au 

Portugal, en URSS et dans plusieurs pays d'Afrique australe et 
centrale.  La bertrandite, dont la teneur en béryllium est 
inférieure à 1%, est cependant devenue la principale source de ce 
métal aux Etats-Unis d'Amérique.  

    La production annuelle mondiale de minerais de béryllium au 
cours de la période 1980 - 84 a été évaluée à environ 10000 tonnes, 
ce qui correspond approximativement à 400 tonnes de béryllium.  
Malgré les fluctuations considérables de l'offre et de la demande 
de béryllium qui résultent de programmes sporadiques de la part des 
gouvernements dans le domaine des armements, de l'énergie nucléaire 
et des activités aérospatiales, on a estimé, en 1986, que la 
demande de béryllium allait vraisemblablement augmenter de 4% par 
an en moyenne jusqu'en 1990.  

    D'une façon générale, les émissions de béryllium au cours de la 
production et de l'utilisation de ce métal sont peu importantes par 
rapport à celles qui se produisent lors de la combustion du charbon 
et du mazout, qui contiennent respectivement 1,8 à 2,2 mg de 
béryllium/kg de poids à sec et jusqu'à 100 µg de béryllium/litre.  
Les émissions de béryllium résultant de la combustion des 
combustibles fossiles correspond aux Etats-Unis, l'un des 
principaux pays producteurs, à environ 93% de l'ensemble des 
émissions de béryllium.  Des mesures de contrôle plus efficaces 
peuvent réduire notablement les émissions de béryllium par les 
centrales thermiques.  

    La concentration de fond en béryllium dans l'air ambiant dépend 
essentiellement de la combustion des combustibles fossiles, mais 
les émissions provenant d'unités de production peuvent conduire 
localement à des concentrations élevées en particulier lorsque les 
mesures antipollution sont insuffisantes.  De même, des émissions 
locales non négligeables peuvent se produire lors de l'essai et de 
l'utilisation de fusées utilisant des propergols à base de 
béryllium.  Dans l'industrie, l'exposition se produit 
principalement lors du traitement des minerais de béryllium, du 
béryllium métallique, des alliages à base de béryllium et de 
l'oxyde de béryllium.  Le béryllium n'est produit qu'au Japon, aux 
Etats-Unis et en URSS.  D'autres pays importent le métal, son oxyde 
ou des alliages aux fins de transformations ultérieures.  

    La plupart des déchets de béryllium font l'objet de mesures de 
lutte antipollution et sont recyclés ou enfouis dans le sol.  La 
plupart des produits de transformation ne peuvent pas être recyclés 
car leur faible volume et leur basse teneur en béryllium font que 
cette opération n'est pas rentable.  

    Environ 72% de la production mondiale de béryllium est utilisée 
sous la forme de cupro-béryllium et d'autres alliages dans les 
industries aérospatiales, électroniques et mécaniques.  Le reste 
est utilisé sous forme d'oxyde de béryllium pour la fabrication de 
céramiques utilisées principalement en électronique et en 

3.  Transport, distribution et transformation dans l'environnement

    On ne dispose que de données limitées sur la destinée du 
béryllium dans l'environnement.  Les particules d'oxyde de 
béryllium en suspension dans l'atmosphère retombent au sol soit à 
sec, soit avec les précipitations.  Dans l'environnement, où le pH 
varie de 4 à 8, le béryllium est fortement absorbé par les minéraux 
sédimentaires finement dispersés, ce qui en empêche le passage dans 
les eaux souterraines.  

    On ne pense pas que le béryllium subisse une bioamplification 
par l'intermédiaire de la chaîne alimentaire.  La plupart des 
plantes fixent le béryllium présent dans le sol en petites 
quantités et la proportion qui parvient jusqu'aux racines ou en 
d'autres parties de la plante reste extrêmement faible.  

4.  Niveaux dans l'environnement et exposition humaine

    La concentration du béryllium dans les eaux de surface et les 
eaux de consommation est généralement de l'ordre du µg/litre.  Dans 
le sol, ces concentrationns se situent entre 1 et 7 mg/kg.  Les 
plantes terrestres en contiennent généralement moins de 1 mg/kg de 
poids à sec.  On a trouvé dans divers organismes marins des 
quantités allant jusqu'à 100 µg/kg de poids frais.  

    En zone rurale aux Etats-Unis on a relevé des concentrations 
atmosphériques allant de 0,03 à 0,06 ng/m3.  Dans les pays où on 
utilise moins de combustibles fossiles, les concentrations de fond 
devraient être plus faibles.  Aux Etats-Unis, les concentrations 
moyennes annuelles dans l'air des villes vont de moins de 0,1 à 6,7 
ng/m3.  Dans des villes japonaises, on a trouvé une moyenne de 0,04 
ng/m3 avec des valeurs maximales (0,2 ng/m3) dans les zones 

    Avant la mise en place de mesures antipollution dans les années 
1950, les concentrations atmosphériques de béryllium étaient très 
fortes au voisinage des unités de production et de transformation 
de ce métal.  En outre, on notait une exposition "para-
professionnelle" dans les familles des travailleurs que l'on 
qualifiait de "cas de voisinage" et qui était due soit à un contact 
avec les vêtements des travailleurs, soit à une exposition 
atmosphérique, soit aux deux.  Aujourd'hui, ce type d'exposition 
est négligeable pour la population dans son ensemble.  La 
principale source d'exposition environnementale impliquant la 
population dans son ensemble est due à la présence de béryllium 
atmosphérique résultant de l'utilisation de combustibles fossiles.  
Il peut se produire des expositions exceptionnellement élevées au 
voisinage de centrales thermiques où l'on brûle du charbon à forte 
teneur en béryllium et où les mesures antipollution ne sont pas 
suffisamment strictes.  La fumée de tabac constitue probablement 
aussi une importante source d'exposition au béryllium.  

    L'utilisation croissante de béryllium en art dentaire pour la 
confection d'appareils pourrait également jouer un certain rôle 
dans l'exposition de la population générale du fait que le 
béryllium a une forte tendance à provoquer des allergies de 

    Avant 1950, l'exposition professionnelle au béryllium était 
généralement très importante et il n'était pas rare de rencontrer 
des concentrations dépassant 1 mg/m3.  Les mesures mises en place 
dans divers pays pour satisfaire aux normes d'exposition 
professionnelle fixées à 1 - 5 µg de Be/m3 (en moyenne pondérée par 
rapport au temps) ont considérablement réduit la concentration du 
béryllium sur les lieux de travail, encore que ces valeurs ne 
soient pas partout respectées.  

    La teneur des tissus ou des liquides biologiques en béryllium 
peut être l'indice d'une exposition antérieure.  Chez des personnes 
qui ne sont pas particulièrement exposées, les concentrations 
urinaires dont d'environ 1 µg/litre et les concentrations dans le 
tissu pulmonaire de moins de 20 µg/kg (de poids à sec).  Les 
quelques données dont on dispose permettent pas d'établir une 
relation bien nette entre l'exposition et la charge de l'organisme, 
encore que l'on trouve indiscutablement des teneurs élevées 
(supérieures à 20 µg/kg) dans les tissus pulmonaires de patients 
atteints de bérylliose.  

5.  Cinétique et métabolisme

    On ne dispose d'aucune donnée sur le dépot et l'absorption du 
béryllium après inhalation.  Les études sur les animaux de 
laboratoire ont montré qu'après dépot dans les poumons, le 
béryllium demeure en place et passe peu à peu dans le sang.  
L'élimination pulmonaire est biphasique, avec une phase 
d'élimination rapide au cours de la première et de la deuxième 
semaine suivant l'arrêt de l'exposition.  

    La majeure partie du béryllium circulant dans le courant 
sanguin s'y trouve sous forme de phosphate colloïdal.  Une part non 
négligeable de la dose inhalée est incorporée au squelette qui 
constitue la site final d'accumulation du béryllium.  En général, 
l'exposition par voie respiratoire entraîne également une 
accumulation prolongée de quantités importantes de béryllium dans 
le tissu pulmonaire, plus particulièrement dans les ganglions 
lymphatiques.  Les dérivés plus solubles vont également se fixer 
dans d'autres tissus ou organes: foie, ganglions lymphatiques 
abdominaux, rate, coeur, muscles, peau et reins.  Après 
administration de béryllium par voie orale, une faible part de 
celui-ci (moins de 1% de la dose) passe en général dans le sang et 
aboutit au squelette.  On en trouve également de petites quantités 
dans les voies digestives et le foie.  

    La résorption du béryllium par la peau intacte est négligeable 
car le béryllium se lie aux constituants de l'épiderme.  

    Une fois absorbé, le béryllium est en très grande partie 
rapidement éliminé dans les urines et en plus faible quantité dans 
les matières fécales.  Le béryllium rejeté par la voie fécale 
provient probablement de l'ingestion des particules éliminées des 
voies respiratoires.  

    Du fait de la rétention du béryllium au niveau sequelettique et 
pulmonaire, sa demi-vie biologique est extrêmement longue.  On 
estime par exemple que chez l'homme elle est de 450 jours dans le 

6.  Effets sur les êtres vivant dans leur milieu naturel

    Les microorganismes terricoles, cultivés dans un milieu pauvre 
en magnésium, se développent mieux en présence de béryllium en 
raison de la substitution partielle du béryllium au magnésium dans 
le métabolisme de ces microorganismes.  Des effets stimulants de ce 
genre ont également été observés chez des algues et des plantes 
cultivées.  Le phénomène semble dépendre du pH car il ne se produit 
qu'à pH élevé.  A pH inférieur ou égal à 7, le béryllium est 
toxique pour les plantes aquatiques et terrestres, quelle que soit 
la teneur en magnésium du milieu de culture.  

    En général, la croissance végétale est inhibée par la présence 
de composés solubles du béryllium à des concentrations de l'ordre 
du mg/litre.  Par exemple dans le cas du haricot commun (Phaseolus 
vulgaris) cultivé dans une solution nutritive à pH 5,3, on observe 
une réduction de 88% du rendement pour une concentration de 5 mg 
Be/litre.  Les effets s'observent d'abord au niveau des racines qui 
virent au brun et ne reprennent pas leur croissance normale.  C'est 
à ce niveau que la majeure partie du béryllium s'accumule, les 
quantités qui passent dans les parties supérieures de la plante 
étant très faibles.  On estime à 3000 mg Be/kg au niveau des 
racines et à 6 mg Be/kg au niveau des feuilles extérieures du chou 
 (Brassica oleracea) en poids à sec, la teneur en béryllium qui 
entraîne une diminution de 50% du rendement.  

    Un rabougrissement des racines et des feuilles a été noté dans 
des cultures de haricots, de blé et de trèfle ladino, mais sans 
chlorose ni tavelure des feuilles.  

    Dans les cultures en pleine terre, la phytotoxicité du 
béryllium dépend de la nature du sol, en particulier de sa capacité 
à échanger les cations et de son pH.  A côté de l'effet de 
substitution au magnésium, la réduction de la phytotoxicité en 
milieu alcalin résulte également de la précipitation de béryllium 
sous forme de phosphate non utilisable.  

    Le mécanisme qui est à la base de la phytotoxicité du béryllium 
repose probablement sur l'inhibition de certaines enzymes 
spécifiques de la plante, en particulier des phosphatases.  Le 
béryllium inhibe également la fixation de certains ions minéraux 

    Les études de toxicité aiguë effectuées sur diverses espèces de 
poissons d'eau douce ont montré que la CL50 allait de 0,15 à 2 mg 
Be/litre selon l'espèce et les conditions expérimentales.  La 
toxicité pour les poissons augmente en raison inverse de la dureté 
de l'eau; le sulfate de béryllium est dix à cent fois plus toxique 
pour les vairons et pour  Lepomis macrochirus dans l'eau douce que 
dans l'eau dure.  Les larves de salamandre et la daphnie  (Daphnia 
 magna) présentent une sensibilité analogue.  

    On ne dispose d'aucune donnée validée sur la toxicité chronique 
du béryllium pour les animaux aquatiques encore qu'une étude non 
publiée ait montré que la daphnie pouvait souffrir de 
concentrations beaucoup plus faibles de béryllium (5 µg Be/litre), 
lors d'études de reproduction à long terme que lors d'études de 
toxicité aiguë (CE50 = 2500 µg Be/litre).  

7.  Effets sur les animaux d'expérience et les systèmes d'epreuves 
 in vitro 

    Chez l'animal d'expérience, les symptômes d'une intoxication 
aiguë par le béryllium se caractérisent par des troubles 
respiratoires, des spasmes, un choc hypoglycémique et une paralysie 

    L'implantation de dérivés du béryllium et de béryllium 
métallique dans les tissus sous cutanés peut produire des 
granulomes analogues à ceux que l'on observe chez l'homme.  On a pu 
faire apparaître une hypersensibilité cutanée chez des cobayes par 
injection intradermique de composés solubles du béryllium.  

    Administré à des ratons, le carbonate de béryllium détermine 
indirectement un rachitisme chez ces animaux, en effet la 
précipitation intestinale du phosphate de béryllium entraîne une 
carence en phosphate.  

    On a observé chez diverses espèces animales l'apparition d'une 
pneumonie chimique aiguë après inhalation de béryllium métallique 
ou de divers composés du béryllium, notamment de dérivés 
insolubles.  Une exposition quotidienne répétée à une nébulisation 
de sulfate de béryllium à la concentration moyenne de 2 mg/m3 s'est 
révélée mortelle pour des rats (mortalité de 90%), des chiens 
(80%), des chats (80%), des lapins (10%), des cobayes (60%), des 
singes (100%), des chèvres (100%), des hamsters (50%) et des souris 
(10%).  En raison de l'effet synergisant de l'ion fluorure, les 
effets du fluorure de béryllium ont été à peu près deux fois plus 
intense que ceux du sulfate.  Certaines de lésions observées dans 
les poumons ressemblaient à celles qu'on voit chez l'homme mais les 
granulomes n'étaient pas identiques.  

    La toxicité de l'oxyde de béryllium insoluble par la voie 
respiratoire dépend en grande partie de ses propriétés physiques et 
chimiques, lesquelles peuvent beaucoup varier selon les conditions 
de production.  Du fait de la granulométrie plus fine de l'oxyde de 
béryllium produit à basse température (400 °C), qui entraîne une 
moindre agrégation, une dose de 3,6 mg Be/m3 pendant 40 jours a 
provoqué une certaine mortalité chez des rats et des lésions 
pulmonaires marquées chez des chiens.  En revanche l'administration 
de deux qualités d'oxyde de béryllium produits à haute température 
(1350 °C et 1150 °C, respectivement) n'a pas produit de lésions 
pulmonaires malgré une exposition totale plus forte (32 mg Be/m3 
pendant 360 heures).  

    La réaction non maligne caractéristique à une exposition 
prolongée par voie respiratoire à de faibles concentrations de 

dérivés du béryllium solubles ou insolubles, est une pneumonie 
chronique avec granulomes, qui ne correspond que partiellement à la 
maladie chronique observée chez l'homme.  

    Les épreuves de génotoxicité effectuées sur cultures de 
cellules somatiques de mammifères montrent que le béryllium réagit 
sur l'ADN et provoque de mutations géniques, des aberrations 
chromosomiques et des échanges entre chromatides soeurs; en 
revanche il n'est pas mutagène dans les systèmes d'épreuves 

    L'injection de béryllium à des lapins par voie intraveineuse 
(3,7 à 700 mg Be) et intramédullaire (0,144 - 216 mg Be), soit sous 
forme métallique soit sous la forme de dérivés, a entraîné 
l'apparition d'ostéosarcomes et de chondrosarcomes avec, chez 40 à 
100% des animaux, des métastases siégeant le plus souvent dans les 

    Chez des rats, l'inhalation (0,8 - 9000 µg Be/m3) ou 
l'intubation trachéenne (0,3-9 mg Be) de béryllium métallique, de 
dérivés solubles et insolubles, et de divers alliages à base de 
béryllium, a provoqué l'apparition de tumeurs pulmonaires de type 
adénome ou adénocarcinome, dont certains donnaient lieu à des 
métastases.  Le béryl (620 µg Be/m3) a été au cours de cette étude 
le seul minerai de béryllium capable de provoquer l'apparition de 
cancers du poumon (ce n'était pas le cas en revanche de la 
bertrandite à 210 µg Be/m3).  L'oxyde de béryllium s'est révélé 
cancérogène pour le rat, mais l'incidence des adénocarcénomes 
pulmonaires était beaucoup plus forte après administration 
intratrachéenne (9 mg Be) d'une qualité d'oxyde produite à basse 
température (51%) qu'avec des oxides produits à haute température 
(11 à 16%).  A l'époque où ces études ont été réalisées, elles 
n'étaient pas conçues ni menées selon les critères actuels et les 
données correspondantes doivent donc être considérées avec beaucoup 
de prudence.  

    L'induction de cancers pulmonaires par le béryllium est très 
spécifique d'espèce.  Alors que les rats et éventuellement les 
singes sont très réceptifs à cet égard, on n'a pas observé de 
tumeurs du poumon chez les lapins, les hamsters ni les cobayes.  

    Trois théories ont été avancées pour expliquer la toxicité du 
béryllium: 1) le béryllium affecterait le métabolisme du phosphate 
en inhibant des enzymes clés, en particulier les phosphatases 
alcalines; 2) le béryllium inhiberait le réplication et la 
prolifération cellulaires en bloquant les enzymes du métabolisme 
des acides nucléiques; enfin 3) la toxicité du béryllium serait due 
à un mécanisme immunitaire, comme le montre l'apparition d'une 
hypersensibilité cutanée à médiation cellulaire chez le cobaye.  

8.  Effets sur l'homme

    Seule l'exposition au béryllium sur les lieux de travail 
présente un intérêt toxicologique.  Avant que ne soient prises dans 
les unités de production de béryllium des mesures de limitations 
des émissions et autres mesures d'hygiène, plusieurs cas de 

"bérylliose de voisinage" avaient été signalés.  En 1966 on avait 
ainsi fait état de 60 cas aux Etats-Unis d'Amérique dont certains 
avaient pu être imputés à des contacts avec les vêtements de 
travailleurs affectés à ces unités de production (exposition 
paraprofessionnelle) ou à une exposition atmosphérique au voisinage 
des unités de production.  Aucun cas de ce type n'a été signalé au 
cours des dernières années.  

    Récemment, on a signalé plusieurs cas de stomatites allergiques 
dus probablement à des prothèses dentaires à base de béryllium.  

    Au cours des années 1930 et 1940, plusieurs centaines de cas de 
bérylliose aiguë se sont déclarés, en particulier chez des 
travailleurs employés dans des unités d'extraction du béryllium en 
Allemagne, en Italie, aux Etats-Unis et en URSS.  L'inhalation de 
sels solubles de béryllium, en particulier le fluorure et le 
sulfate à des concentrations supérieures à 100 µg Be/m3, produisait 
systématiquement des symptômes aigus chez presque tous les 
travailleurs exposés, alors qu'aux concentrations inférieures ou 
égales à 15 µg/m3 (déterminées avec des méthodes d'analyse 
aujourd'hui périmées) aucun cas n'était enregistré.  Après 
l'adoption, au début des années 1950, d'une limite maximale 
d'exposition de 25 µg/m3, on a constaté une diminution très marquée 
des cas de bérylliose aiguë.  

    La symptomatologie le la bérylliose aiguë comporte des 
manifestations qui vont de la simple inflammation des muqueuses 
nasales et pharyngées à la trachéobronchite et à la pneumonie 
chimique grave.  Dans les cas graves, les malades peuvent mourir de 
pneumonie aiguë mais la plupart du temps, la guérison est totale 
une à quatre semaines après cessation de l'exposition.  Dans 
quelques rares cas, une bérylliose chronique peut se manifester 
plusieurs années après guérison de la forme aiguë.  

    Un contact direct avec des composés solubles entraîne une 
dermatite de contact et éventuellement une conjonctivite.  Les 
individus sensibles réagissent beaucoup plus rapidement et à des 
concentrations plus faibles.  Introduit dans ou sous l'épiderme, 
les composés solubles ou insolubles du béryllium produisent des 
ulcérations chroniques avec apparation fréquente de granulomes au 
bout de plusieurs années.  

    La bérylliose chronique se distingue de la forme aiguë par sa 
période de latence qui peut aller de quelques semaines à plus de 20 
ans; elle est longue et de gravité progressive.  Le US Beryllium 
Case Registry (Registre des cas de bérylliose des Etats-Unis 
d'Amérique) constitue un fichier central où sont enregistrés les 
cas de bérylliose.  Il a été créé en 1952 et 888 cas y ont été 
consignés entre cette date et 1983.  Parmi ces cas, 622 ont été 
classés comme chroniques, dont 557 attribuables à une exposition 
professionnelle, soit dans l'industrie des lampes à fluorescence 
(319 cas) soit dans des unités d'extraction du béryllium (101 cas).  
Après l'abandon en 1949 de l'utilisation de silicate double de zinc 
et de béryllium et d'oxyde de béryllium pour la production de 
phosphores destinés aux tubes à fluorescence et la fixation d'une 

limite d'exposition professionnelle (TWA = 2 µg Be/m3), les cas de 
bérylliose chronique ont diminué de façon spectaculaire, mais on a 
en revanche enregistré de nouveaux cas qui résultaient d'une 
exposition à du béryllium présent dans l'atmosphère à la 
concentration d'environ 2 µg/m3.  

    Il est préférable de parler d'ailleurs de "maladie chronique du 
béryllium" plutôt que de "bérylliose" car il s'agit d'une maladie 
différente d'une pneumoconiose typique.  Les caractéristiques 
principales en sont une inflammation granulomateuse du poumon, 
associée à une dyspnée d'effort, à de la toux, des douleurs 
thoraciques, une fatigue et une faiblesse générales.  On peut 
également observer une hypertrophie ventriculaire droite avec 
insuffisance cardiaque, une hépatomégalie, une splénomégalie, une 
cyanose et un hippocratisme digital.  On a également constaté que 
la maladie s'accompagnait de modifications des protéines sériques 
et de la fonction hépatique, de calculs rénaux et d'ostéosclérose.  
L'évolution n'est pas uniforme; quelques fois il y a rémission 
spontanée pendant des semaines ou des années, puis exacerbation.  
Dans la majorité des cas, on observe une pneumopathie progressive 
avec risque accru de décès par insuffisance cardiaque ou 
respiratoire.  Le taux de morbidité chez les ouvriers de 
l'industrie du béryllium varie de 0,3 à 7,5%.  Chez les patients 
atteints de la maladie chronique, la mortalité peut monter jusqu'à 

    L'examen macroscopique des poumons révèle des altérations 
diffuses avec fibrose interstitielle et envahissement du parenchyme 
par de petits nodules disséminés.  Du point du vue histologique, on 
observe de granulomes de type sarcoïde avec une inflammation 
interstitielle de degré variable; ces aspects ne se distinguent 
généralement pas de ceux qu'offrent les autres granulomatoses 
telles que la sarcoïdose ou la tuberculose.  

    L'anamnèse et l'analyse des tissus sont utiles au diagnostic de 
la bérylliose encore que la présence de béryllium dans les 
prélèvements ne soit pas une preuve de la maladie.  La cuti-
réaction n'est pas recommandée car il s'agit là d'une méthode peu 
fiable et très sensibilisante.  Les examens de laboratoire les plus 
utilisés sont l'épreuve d'inhibition de la migration des 
macrophages et le test de transformation lymphoblastique.  

    Ces méthodes de mesure de l'hypersensibilité reposent sur un 
mécanisme immunitaire qui est probablement à la base de la 
bérylliose chronique et de l'hypersensibilité cutanée et 
granulomateuse retardées.  

    Les variations considérables du temps de latence et l'absence 
de relation dose-réponse dans la bérylliose chronique peuvent 
s'expliquer par une sensibilisation immunologique.  Il semble que 
la grossesse joue le rôle d'un "facteur de stress" précipitant car 
66% des 95 femmes figurant parmi les cas mortels de bérylliose 
enregistrés dans le US Beryllium Case Registry, étaient 
effectivement enceintes.  

    A l'origine de l'exposition des malades, on peut citer 
également la production d'alliages à base de béryllium, l'usinage 
de pièces en béryllium, l'industrie des céramiques (production et 
recherche), la recherche et la production d'énergie.  Les normes 
actuelles d'exposition professionnelle ne protègent pas 
véritablement les individus sensibles contre la bérylliose 

    Lors d'un certain nombre d'études épidémiologiques, on a 
examiné la cancérogénicité du béryllium chez les ouvriers de deux 
unités de production aux Etats-Unis d'Amérique et l'on a également 
compulsé un registre de cas de bérylliose pulmonaire, où figuraient 
des employés de ces unités et d'autres branches d'activité.  Les 
résultats de ces études ont été discutés en raison de la 
possibilité d'un biais sélectif, de l'existence de facteurs de 
confusion dus au tabagisme et de la sous estimation du nombre 
attendu de décès par cancer du poumon, étant donné que les taux de 
mortalité pour la période 1965 - 67 avaient été utilisés pour 
calculer la mortalité prévue en 1968 - 75.  Il est peu probable que 
les deux premiers points aient pu contribuer de façon importante à 
accroître le risque de cancer du poumon; en revanche, les données 
qui figurent dans ce document sont fondées sur des prévisions 
"corrigées" du nombre de décès par cancer du poumon.  Toutes les 
études effectuées ont fait ressortir une augmentation significative 
du risque de cancer du poumon.  

9.  Evaluation des risques pour la santé humaine et des effets sur 

9.1 Risques pour la santé humaine

    Dans la mesure où l'industrie du béryllium applique des mesures 
antipollution convenables, l'exposition de la population générale 
se limite actuellement à de faibles concentrations de béryllium 
atmosphérique résultant de l'utilisation de combustibles fossiles.  
Dans certains cas exceptionnels, où l'on utilise un charbon 
excessivement riche en béryllium, il pourrait se poser des 
problèmes de santé.  L'utilisation du béryllium pour la confection 
de prothèses dentaires est à revoir du fait du pouvoir 
sensibilisateur très important de cette substance.  

    Les cas de bérylliose aiguë se manifestant sous la forme de 
rhinopharyngites, de bronchites et de pneumonies chimiques graves 
se sont réduits de façon spectaculaire et aujourd'hui, ils ne 
pourraient se produire qu'en cas de panne des systèmes 
antipollution.  La bérylliose chronique se distingue de la forme 
aiguë par sa très longue période de latence qui peut aller de 
quelques semaines à plus de 20 ans et par sa gravité progressive.  
C'est essentiellement les poumons qui sont touchés.  Cette 
affection se caractérise par une inflammation granulomateuse du 
tissu pulmonaire avec dyspnée d'effort, toux, douleurs thoraciques, 
perte de poids et faiblesse générale.  Les effets sur les autres 
organes sont probablement dus à des causes indirectes.  Cette 
affection peut encore s'observer chez des individus sensibilisés 
exposés à des concentrations d'environ 2 µg/m3; elle se caractérise 
par de grandes variations dans le temps de latence et l'absence de 
relation dose-réponse.  

    Malgré un certain nombre d'insuffisances dans la conception des 
études et les pratiques de laboratoire, l'activité cancérogène du 
béryllium chez diverses espèces animales est confirmée.  

    Un certain nombre d'études épidémiologiques ont montré que 
l'exposition professionnelle au béryllium comportait un risque 
accru de cancer du poumon.  L'interprétation des résultats obtenus 
a fait l'objet d'un certain nombre de critiques mais les données 
disponibles permettent de conclure que c'est très vraisemblablement 
le béryllium qui est à l'origine de l'accroissement du risque de 
cancer pulmonaire observé chez les travailleurs exposés.  

9.2 Effets sur l'environnement

On ne dispose que de données limitées sur la destiné du béryllium 
dans l'environnement et notamment au sujet des effets qu'il exerce 
sur les organismes aquatiques et terrestres.  Les concentrations en 
béryllium dans les eaux superficielles (de l'ordre du µg/litre) et 
dans les sols (de l'ordre du µg/kg de poids sec) sont généralement 
faibles et n'ont probablement pas d'effets nocifs sur 


1.  Identidad, propiedades fisicas y químicas, métodos de análisis

    El berilio es un metal quebradizo de color gris acero, cuyo 
único isótopo natural es el 9Be.  Sus compuestos son bivalentes.  
El berilio posee varias propiedades excepcionales.  Es la más 
liviana de todas las sustancias sólidas y químicamente estables y 
tiene una temperatura de fusión, un calor específico, un calor de 
fusión y una resistencia por relación al peso excepcionalmente 
elevados.  Posee excelentes propiedades de conductividad y 
conductibilidad.  Debido a su pequeño número atómico, el berilio es 
muy permeable a los rayos X.  Sus propiedades nucleares incluyen la 
ruptura, dispersión y reflexión de neutrones, así como la emisión 
de neutrones por bombardeo-alpha.  

    El berilio tiene una serie de propiedades químicas en común con 
el aluminio, especialmente su gran afinidad por el oxígeno.  Esta 
hace que en la superficie del berilio metálico y de las aleaciones 
de berilio se forme una película muy estable de óxido de berilio 
(BeO) que los hace muy resistentes a la corrosión, el agua y los 
ácidos oxidantes en frío.  Cuando se inflama en oxígeno, el polvo 
de berilio arde a una temperatura de 4500 °C.  El óxido de berilio 
sinterizado ("berilia") es muy estable y posee propiedades 
cerámicas.  Las sales catiónicas de berilio se hidrolizan en agua y 
reaccionan formando hidróxidos insolubles o complejos hidratados, 
cuando los valores de pH varían entre 5 y 8, y berilatos cuando el 
pH es superior a 8.  

    El berilio, como aditivo para aleaciones, confiere una 
combinación de propiedades notables a otros metales, especialmente 
la resistencia a la corrosión, un gran módulo de elasticidad, 
características no magnéticas y no pirofóricas, mayor conductividad 
y conductibilidad, además de una resistencia superior a la del 

    Se han utilizado diversos métodos analíticos para determinar la
presencia de berilio en diferentes medios.  Los métodos más antiguos
incluyen técnicas de espectroscopia, fluorimetría y
espectrofotometría.  La espectrometría de absorción atómica sin
llama y la cromatografía de gases son los métodos de elección; los
límites de detección son de 0,5 ng/muestra (absorción atómica sin
llama) y de 0,04 pg/muestra (cromatografía de gases con detección
por captura de electrones).  Además, cada vez se emplea más la
espectrometría de emisión atómica de plasma acoplado por inducción. 

2.  Fuentes de exposicion humana y ambiental

    El berilio es el 35° elemento más abundante en la corteza 
terrestre, con un contenido medio de unos 6 mg/kg.  Aparte de las 
gemas, la esmeralda (berilo que contiene cromo) y la aguamarina 
(berilo que contiene hierro), sólo 2 minerales de berilio tienen 
importancia económica.  El berilo contiene hasta un 4% de berilio y 
se extrae en la Argentina, el Brasil, la India, China, Portugal, la 
URSS y en varios países de Africa meridional y central.  La 
bertrandita se ha convertido en la principal fuente de este metal 
en los EE.UU., pese a que contiene menos del 1% de berilio.  

    La producción mundial anual de minerales de berilio en 1980 - 
1984 fue de aproximadamente 10 000 toneladas, lo que corresponde a 
unas 400 toneladas de berilio.  Pese a las considerables 
fluctuaciones en la oferta y la demanda de berilio debidas a 
esporádicos programas gubernamentales en armamento, energía nuclear 
e industrias aeroespaciales, se prevía, en 1986, que la demanda dé 
berilio aumentaría en un promedio anual de un 4% hasta 1990.  

    Por lo general, las emisiones de berilio durante su producción 
y utilización son poco importantes comparadas a las emisiones que 
ocurren durante la combustión de carbón y el fuel, que poseen un 
contenido natural medio de 1,8 - 2,2 mg Be/kg de peso seco y hasta 
100 µg Be/litro, respectivamente.  La emisión de berilio por 
utilización de combustibles fósiles representó aproximadamente el 
93% de la emisión total de berilio en los EE.UU., uno de los 
principales países productores.  Si se mejoran las medidas de 
control de las emisiones, podrá reducirse considerablemente la 
emisión de berilio de las centrales termoeléctricas.  

    Si bien la utilización de combustibles fósiles determina la 
concentración general de berilio en la atmósfera, las fuentes 
relacionadas con la producción pueden dar lugar a concentraciones 
ambientales localmente elevadas, especialmente donde las medidas de 
control son insuficientes.  Igualmente, las emisiones producidas 
por la experimentación y el uso de cohetes impulsados por berilio 
podrían tener gran importancia a nivel local.  La exposición 
ocupacional ocurre sobre todo durante el procesado de minerales de 
berilio, berilio metálico, aleaciones con berilio y óxido de 
berilio.  Los únicos países con industrias productivas son el 
Japón, los EE.UU.  y la URSS.  En otros países, el metal puro, las 
aleaciones o el óxido de berilio cerámico importados son 
transformados en productos finales.  

    La mayor parte de los desechos del berilio provienen de medidas 
anticontaminantes y son reciclados o enterrados.  El reciclado de 
la mayoría de los productos finales no es rentable debido a su 
pequeño volumen y bajo contenido en berilio.  

    Aproximadamente el 72% de la producción mundial de berilio se 
utiliza en forma berilio-cobre y otras aleaciones en las industrias 
aeroespacial, electrónica y mecánica.  Alrededor de un 20% se 
utiliza como metal libre sobre todo en las industrias aeroespacial, 
de armamento y nuclear.  El resto se emplea como óxido de berilio 
para aplicaciones cerámicas, principalmente en electrónica y 

3.  Transporte, distribucion y transformación en el medio ambiente

    Los datos sobre la suerte que corre el berilio en el medio 
ambiente son limitados.  Las partículas de óxido de berilio 
atmosférico regresan a la tierra por sedimentación húmeda y seca.  
Dentro de los valores del pH ambiental, entre 4 y 8, los minerales 
sedimentarios finamente dispersos fijan el berilio, evitando así 
que pase a las aguas subterráneas.  

    Parece que el berilio no se biomultiplica en absoluto en las 
cadenas alimentarias.  La mayoría de las plantas absorben berilio 
del suelo en pequeñas cantidades, y sólo una parte ínfima pasa de 
las raíces a otras partes de la planta.  

4.  Concentraciones ambientales y exposición humana

    Las concentraciones de berilio en las aguas superficiales y de 
bebida suelen ser de unos pocos µg/litro.  Las concentraciones en 
los suelos varían entre 1 y 7 mg/kg.  Por lo general, las plantas 
terrestres contienen menos de 1 mg de berilio por kg de peso seco.  
En diversos organismos marinos se han encontrado concen-traciones 
de aproximadamente 100 µg/kg de peso en fresco.  

    Se observaron variaciones de la concentración de berilio 
atmosférico en zonas rurales de los EE.UU.  de 0,03 a 0,06 ng/m3.  
En los países donde se queman menos combustibles fósiles es 
probable que las concentraciones ambientales sean inferiores.  Se 
observó que las concentraciones medias anuales de berilio en el 
aire urbano de los EE.UU.  variaban entre <0,1 y 6,7 ng/m3.  En 
las ciudades japonesas se encontró un promedio de 0,04 ng/m3, con 
valores máximos (0,2 ng/m3) en las zonas industriales.  

    Antes de que se establecieran las medidas de control en los 
años cincuenta, las concentraciones de berilio en la atmósfera eran 
sumamente elevadas en las cercanías de las plantas de producción y 
procesamiento.  Además, se daban frecuentes casos de exposición 
"paraocupacional" en las familias de los trabajadores, denominados 
casos de vecindad, debidos al contacto con la ropa del trabajador, 
o a la exposición atmosférica, o a ambos.  Hoy en día, esas fuentes 
de exposición suelen ser insignificantes para la población en 
general.  La fuente principal de exposición ambiental de la 
población general al berilio atmosférico es el empleo de 
combustibles fósiles.  Excepcionalmente, también puede haber una 
exposición elevada en las cercanías de centrales eléctricas donde 
se queme carbón con altas concentraciones de berilio y no se 
apliquen las medidas de control adecuadas.  Probablemente, fumar 
tabaco también sea una fuente importante de exposición al berilio.  

    El creciente uso del berilio en la base de aleaciones para 
piezas dentales podría tener cierta importancia para la población 
general, debido al gran potencial del berilio de provocar 
reacciones alérgicas por contacto.  

    Antes de 1950, la exposición al berilio en los lugares de 
trabajo era a menudo muy elevada; no era raro encontrar 
concentraciones superiores a 1 mg/m3.  Las medidas de control 
establecidas en distintos países para responder a las normas 
ocupacionales de 1 - 5 µg Be/m3 (promedio ponderado por el tiempo) 
redujeron drásticamente dichas concentraciones, aunque todavía no 
se han alcanzado estos valores en todas partes.  

    La presencia de berilio en tejidos y líquidos orgánicos puede 
ser indicativa de una exposición anterior.  Las personas sin 
exposición específica presentan valores en la orina de alrededor de 

1 g/litro y en el tejido pulmonar inferiores a 20 g/kg (peso seco).  
Los datos limitados de que se dispone no permiten establecer una 
clara relación entre exposición y concentración en el cuerpo, si 
bien se han encontrado valores elevados (20 g/kg) en muestras de 
tejido pulmonar de pacientes con la enfermedad del berilio.  

5.  Cinética y metabolismo

    No se dispone de datos sobre el depósito o la absorción del 
berilio inhalado en el hombre.  Los estudios en animales han 
demostrado que, tras depositarse en los pulmones, el berilio 
permanece en ellos y es absorbido lentamente en la sangre.  La 
capacidad de autodepuración pulmonar es bifásica, con una fase de 
eliminación rápida durante las primeras 1 - 2 semanas después de 
haber cesado la exposición.  

    La mayor parte del berilio que circula en la sangre es 
transportado en forma de fosfato coloidal.  Una parte importante de 
la dosis inhalada se incorpora en el esqueleto, siendo éste el 
lugar final donde se almacena el berilio.  Generalmente, la 
exposición por inhalación tiene como consecuencia un almacenamiento 
a largo plazo de cantidades apreciables de berilio en el tejido 
pulmonar, particularmente en los nódulos linfáticos pulmonares.  
Los compuestos más solubles de berilio son también transportados al 
hígado, los nódulos linfáticos abdominales, el bazo, el corazón, el 
músculo, la piel y el riñón.  

    Por lo común, tras la administración oral de berilio, una 
pequeña cantidad (menos del 1%) era absorbida en la sangre y 
almacenada en el esqueleto.  También se encontraron pequeñas 
cantidades en el tracto gastrointestinal y en el hígado.  

    La absorción de berilio por la piel intacta es insignificante, 
puesto que los constituyentes de la epidermis fijan el berilio.  

    Una proporción considerable del berilio absorbido se elimina 
rápidamente, sobre todo por la orina y, en cierta medida, por las 
heces.  Una parte del berilio inhalado se elimina en las heces, 
probablemente como resultado de la capacidad de autodepuración del 
tracto respiratorio y la ingestión de berilio por vía oral.  

    Debido al prolongado almacenamiento del berilio en el esqueleto 
y los pulmones, su semivida biológica es sumamente larga.  En el 
caso del hombre se ha calculado que la semivida permanece 450 días 
en el esqueleto.  

6.  Efectos en los organismos del medio ambiente

    Los microorganismos del suelo cultivados en un medio deficiente 
en magnesio crecen mejor en presencia de berilio, debido a la 
sustitución parcial del magnesio por el berilio en el metabolismo 
de los organismos.  Se observaron efectos similares de estimulación 
del crecimiento en algas y en plantas cultivadas.  Al parecer este 
fenómeno depende del pH, ya que ocurre únicamente cuando el pH es 
elevado.  Cuando el pH es igual o inferior a 7, el berilio es 

tóxico para las plantas acuáticas y terrestres, sean cuales sean 
las concentraciones de magnesio en el medio de crecimiento.  

    En general, los compuestos de berilio solubles inhiben el 
crecimiento de las plantas en concentraciones de mg/litro.  Por 
ejemplo, en habichuelas  (Phaseolus vulgaris) cultivadas en una 
solución nutritiva con un pH 5,3, se observó una reducción del 
rendimiento del 88% con una concentración de 5 mg Be/litro.  Los 
efectos se observaron en primer lugar en las raíces, que se 
oscurecieron y dejaron de elongarse normalmente.  Las raíces 
acumulan la mayor parte del berilio absorbido y sólo una pequeña 
cantidad es transportada a las partes superiores de la planta.  Se 
estimó que el contenido crítico de berilio que reduce un 50% el 
rendimiento es de unos 3000 mg Be/kg en las raíces y de unos 6 mg 
Be/kg en las hojas externas de las plantas de col  (Brassica 
 oleracea) en base al peso seco.  

    En alubias, trigo y trébol ladino cultivados en tierra se 
observó atrofia radicular y foliar, pero no clorosis ni manchas en 
las hojas.  

    En los cultivos en tierra, la fitotoxicidad del berilio está 
regida por las características del suelo, en particular su 
capacidad de intercambio catiónico y el pH de la solución del 
suelo.  Aparte del efecto de sustitución del magnesio, la 
disminución de la fitotoxicidad en condiciones alcalinas también se 
debe a la precipitación del berilio en forma no disponible como sal 
de fosfato.  

    El mecanismo responsable de la fitotoxicidad del berilio se 
basa probablemente en la inhibición de enzimas específicas, 
especialmente las fosfatasas vegetales.  El berilio también inhibe 
la absorción de iones minerales esenciales.  

    En estudios de toxicidad aguda con diferentes especies de peces 
de agua dulce, se observaron valores de CL50 de 0,15 a 2 mg 
Be/litro, según la especie y las condiciones experimentales.  La 
toxicidad para los peces aumentaba cuando disminuía la dureza del 
agua; el sulfato de berilio era más tóxico en uno o dos órdenes de 
magnitud para  Pinephales promelas y  Leponis macrochirus en agua             
blanda que en agua dura.  Las larvas de salamandra y la pulga de 
agua  Daphnia magna mostraron una sensibilidad similar.  

    No existen datos validados sobre la toxicidad crónica del 
berilio en animales acuáticos, si bien en un estudio inédito se 
observó que  Daphnia magna se veía afectada adversamente por 
concentraciones de berilio bastante menores (5 µg Be/litro) en las 
pruebas de reproducción a largo plazo que en las pruebas de 
toxicidad aguda (CE50 2500 µg Be/litro).  

7.  Efectos en animales de experimentación y en sistemas de ensayo 
 in vitro

    Los síntomas de envenenamiento agudo con berilio que se 
manifestaron en los animales de experimentación fueron trastornos 
respiratorios, espasmos, choque hipoglucémico y parálisis 

    La implantación de compuestos de berilio y de berilio metálico 
en los tejidos subcutáneos puede producir granulomas similares a 
los observados en el ser humano.  En el cobayo apareció 
hipersensibilidad tras la inyección de compuestos solubles de 
berilio por vía intradérmica.  

    Como efecto secundario, el carbonato de berilio produjo 
raquitismo en ratas jóvenes por la precipitación intestinal de 
fosfato de berilio y la correspondiente privación de fósforo.  

    Varias especies animales presentaron neumonitis químicas agudas 
tras la inhalación de metal de berilio o de diferentes compuestos 
de berilio, incluso las formas insolubles.  Las exposiciones 
diarias repetidas a vahos de sulfato de berilio, de una 
concentración media de 2 mg Be/m3, fueron letales para la rata (90% 
de muertes), el perro (80%), el conejo (10%), el cobayo (60%), el 
mono (100%), la cabra (100%), el hámster (50%) y el ratón (10%).  
Debido al efecto sinérgico del ion fluoruro, los efectos del 
fluoruro de berilio fueron unas dos veces superiores a los de los 
sulfatos.  Algunas de las lesiones en los pulmones eran parecidas a 
las observadas en el hombre, pero los granulomas no eran idénticos.  

    La toxicidad de la inhalación de óxido de berilio insoluble 
depende en gran parte de sus propiedades físicas y químicas, que 
pueden variar considerablemente según las condiciones de 
producción.  Debido a que el tamaño mínimo de las partículas es más 
pequeño y la agregación es menor, la exposición a BeO caldeado a 
baja temperatura (400 °C) a 3,6 mg Be/m3 durante 40 días fue causa 
de mortalidad en ratas y de graves lesiones pulmonares en perros.  
El BeO caldeado a dos temperaturas elevadas distintas (1350 °C y 
1150 °C) no causó lesiones pulmonares, pese a que la exposición 
total fue mayor (32 mg Be/m3, 360 h).  

    La respuesta no maligna característica a la exposición a largo 
plazo por inhalación de concentraciones menores de compuestos de 
berilio solubles e insolubles es una neumonitis crónica asociada a 
granulomas, que sólo corresponde en parte a la enfermedad crónica 
en el ser humano.  

    Los resultados de las pruebas de genotoxicidad indican que el 
berilio interacciona con el ADN y causa mutaciones de genes, 
aberraciones cromosómicas y un intercambio de cromátidas hermanas 
en cultivos de células somáticas de mamíferos, aunque no presenta 
efectos mutagénicos en sistemas bacterianos de ensayo.  

    La inyección intravenosa (3,7 - 700 mg Be) e intramedular 
(0,144 - 216 mg Be) de berilio metálico y de diversos compuestos 
produjo osteosarcomas y condrosarcomas en conejos, con la aparición 
de metástasis en un 40 - 100% de los animales, especialmente en el 

    En ratas, la inhalación (0,8 - 9000 µg Be/m3) o la exposición
intratraqueal (0,3 - 9 mg Be) a compuestos solubles o insolubles de
berilio, berilio metálico, y diversas aleaciones de berilio indujo
tumores pulmonares del tipo del adenoma o del adenocarcinoma,
parcialmente metastatizante.  El berilio (620 µg Be/m3) fue el
único mineral de berilio que produjo carcinomas pulmonares (no así

la bertrandita a 210 µg Be/m3).  El óxido de berilio resultó ser
carcinogénico para la rata, pero la incidencia de adenocarcinomas
pulmonares fue mucho mayor tras la administración intratraqueal (9
mg Be) de una especificación caldeada a baja temperatura (51%), en
comparación con la de óxidos caldeados a alta temperatura (11 -
16%).  En la época en que se realizaron muchos de estos estudios, la
concepción de los estudios y las prácticas de laboratorio no solían
ajustarse a las prácticas actuales, por lo que conviene considerar
con especial precaución los datos comunicados sobre inhalación.  

    La inducción de cáncer del pulmón por el berilio varía mucho de 
unas especies a otras.  Mientras que la rata y quizá el mono son 
muy susceptibles a este respecto, no se han observado tumores 
pulmonares en el conejo, el hámster ni el cobayo.  

    Existen tres teorías en cuanto a los mecanismos de toxicidad 
del berilio: 1) el berilio incide en el metabolismo del fosfato ya 
que inhibe enzimas cruciales, en particular la fosfatasa alcalina; 
2) el berilio inhibe la replicación y la proliferación celular ya 
que afecta a las enzimas del metabolismo de los ácidos nucleicos; y 
3) en la toxicidad del berilio interviene un mecanismo 
inmunológico, como se ha observado en el cobayo, que desarrolla una 
hipersensibilidad cutánea de mediación celular.  

8.  Efectos en el hombre

    La exposición al berilio de importancia toxicológica se limita 
casi exclusivamente al lugar de trabajo.  Antes de la introducción 
de medidas mejores de control de la emisión y de higiene en las 
plantas de berilio, se registraron varios casos de "vecindad" de la 
enfermedad crónica del berilio.  Hasta 1966 se habían registrado un 
total de 60 casos en los EE.UU., algunos de ellos por contacto con 
la ropa de los trabajadores (exposición "paraocupacional") o 
exposición a la atmósfera en las cercanías de las plantas de 
berilio.  En los últimos años no se ha notificado ningún caso.  

    Recientemente, se han notificado varios casos de estomatitis 
alérgica por contacto, ocasionada probablemente por prótesis 
dentales que contienen berilio.  

    En los años treinta y cuarenta hubo varios centenares de casos 
de enfermedad aguda del berilio, sobre todo entre los trabajadores 
de las plantas de extracción de berilio en Alemania, Italia, los 
EE.UU.  y la URSS.  La inhalación de sales solubles de berilio, 
especialmente el fluoruro y el sulfato, en concentraciones 
superiores a 100 µg Be/m3, produjo síntomas agudos en casi todos 
los trabajadores expuestos, mientras que con concentraciones 
iguales o menores a 15 µg/m3 (determinadas por métodos analíticos 
anticuados), no se registró ningún caso.  Tras la adopción a 
principios de los años cincuenta de la concentración máxima de 
exposición de 25 µg/m3, hubo una disminución drástica de los casos 
de la enfermedad aguda del berilio.  

    Los signos y síntomas de la enfermedad aguda del berilio varían 
desde una leve inflamación de las mucosas nasales y la faringe 
hasta una traqueobronquitis y neumonitis química grave.  En los 

casos graves, los pacientes fallecieron de neumonitis aguda, pero 
en la mayoría de los casos, al cesar la exposición se produjo una 
recuperación total en el lapso de 1 - 4 semanas.  En algunos casos, 
la enfermedad crónica del berilio se desarrolló años después de la 
recuperación de la forma aguda de la enfermedad.  

    El contacto directo con compuestos solubles de berilio produce 
dermatitis por contacto y posiblemente conjuntivitis.  Los 
individuos sensibilizados reaccionan mucho antes y a cantidades 
menores de berilio.  La introducción cutánea o subcutánea de 
compuestos de berilio solubles o insolubles produce ulceraciones 
crónicas; a menudo aparecen granulomas al cabo de varios años.  

    La enfermedad crónica del berilio difiere de la forma aguda en 
que tiene un periodo de latencia que varía desde unas semanas hasta 
más de 20 años; es además de larga duración y de gravedad 
progresiva.  En el registro oficial central de casos de enfermedad 
del berilio de los EE.UU., creado en 1952, se habían registrado 888 
casos hasta 1983.  Seiscientos veintidós se clasificaron como 
crónicos, de los cuales 557 se debían a la exposición ocupacional, 
sobre todo en la industria de lámparas fluorescentes (319 casos) o 
en las plantas de extracción de berilio (101 casos).  A partir de 
1949, cuando se abandonó el uso del silicato de berilio y zinc y 
del óxido de berilio en los fósforos de tubos fluorescentes y se 
adoptó un límite de exposición ocupacional (TWA, 2 µg Be/m3), el 
número de casos de enfermedad crónica del berilio disminuyó 
ostensiblemente, si bien se han registrado nuevos casos como 
consecuencia de la exposición a una concentración en el aire de 
unos 2 µg/m3.  

    El término "enfermedad crónica del berilio" se prefiere al de 
"beriliosis" debido a que esta enfermedad difiere de la típica 
neumoconiosis.  Las características más típicas son la inflamación 
granulomatosa del pulmón, asociada a una disnea tras un esfuerzo, 
tos, dolor de pecho, pérdida de peso, fatiga y debilidad general; 
también puede darse una hipertrofia del corazón derecho con el 
consiguiente fallo cardiaco, hepatomegalia, esplenomegalia, 
cianosis y dedos en palillo de tambor.  Asimismo, se han observado, 
asociados a la enfermedad crónica del berilio, cambios en las 
proteínas séricas y la función hepática, cálculos renales y 
osteoesclerosis.  La evolución de la enfermedad crónica del berilio 
no es uniforme; en algunos casos se observa una remisión espontánea 
durante semanas o años, seguida de exacerbaciones.  En la mayoría 
de los casos, se observa una enfermedad pulmonar progresiva con un 
mayor riesgo de muerte por fallo cardiaco o respiratorio.  Se han 
notificado tasas de morbilidad entre los trabajadores del berilio 
que varían entre 0,3 y 7,5%.  En los pacientes con enfermedad 
crónica del berilio las tasas de mortalidad alcanzan hasta el 37%.  

    A nivel macroscópico los pulmones pueden presentar cambios 
difusos, con pequeños nódulos muy dispersos y fibrosis 
intersticial.  A nivel microscópico, existen granulomas de tipo 
sarcoide con diferentes grados de inflamación intersticial, que 
generalmente no pueden diferenciarse de los observados en otras 
granulomatosis como la sarcoidosis o la tuberculosis.  

    Para diagnosticar la enfermedad crónica del berilio, son de 
gran utilidad el historial y un análisis de tejido, aunque la 
presencia de berilio en el material biológico no constituye una 
prueba de que haya enfermedad.  Las pruebas alérgicas no son 
recomendables, dado que no son muy fiables y ellas mismas producen 
una alta sensibilización.  Los elementos más útiles para el 
diagnóstico son el ensayo de inhibición de la migración de 
macrófagos y la prueba de transformación de linfocito-blastos.  

    Estos métodos que miden la hipersensibilidad se basan en un 
mecanismo inmune que probablemente es subyacente a la enfermedad 
crónica del berilio y la tardía hispersensibilidad cutánea y 

    En la enfermedad crónica del berilio, la sensibilización 
inmunológica podría explicar la gran variabilidad de la latencia y 
la falta de relación entre la dosis y la respuesta.  El embarazo 
parece ser un "factor de estrés" desencadenante, puesto que el 66% 
de las 95 mujeres registradas entre los casos mortales del registro 
de casos de enfermedad del berilio en los EE.UU.  estaban 

    Las fuentes de exposición de los pacientes con la enfermedad 
del berilio incluyen la producción de aleaciones metálicas de 
berilio, maquinarias, la investigación y producción de cerámicas, y 
la producción de energía.  Es posible que las actuales normas de 
exposición ocupacional no basten para impedir la aparición de la 
enfermedad crónica del berilio en individuos sensibilizados.  

    La carcinogenicidad del berilio ha sido examinada en varios 
estudios realizados sobre los trabajadores empleados en dos 
instalaciones de producción de berilio en los EE.UU.  y en un 
registro de casos clínicos de afecciones pulmonares relacionadas 
con el berilio; el registro procedía de estas instalaciones y de 
otras ocupaciones.  Los resultados de estos estudios fueron puestos 
en tela de juicio debido al sesgo en la selección, a la confusión 
con los efectos de fumar cigarrillos y a que se subestimó el número 
de muertes previstas por cáncer del pulmón, dado que se utilizaron 
las tasas de mortalidad correspondientes al periodo 1965 - 1967 
para hacer una estimación de la mortalidad prevista para los años 
1968 - 1975.  Si bien es poco probable que los dos primeros 
factores desempeñen un papel importante en el exceso de riesgo de 
cáncer del pulmón, los datos que se dan en este documento se basan 
en un "ajuste" del número de muertes previstas por cáncer del 
pulmón.  Todos los estudios realizados señalaban riesgos 
significativamente elevados de cáncer del pulmón.  

9.  Evaluacion de los riesgos para la salud humana y los efectos en 
el medio ambiente

9.1 Riesgos para la salud humana

    Siempre y cuando las medidas de control en la industria del 
berilio sean adecuadas, la exposición de la población general hoy 
en día se limita a pequeñas concentraciones de berilio en la 

atmósfera, procedente de la utilización de combustibles fósiles.  
En casos excepcionales, cuando se quema carbón con un contenido de 
berilio desusadamente alto, pueden surgir problemas de salud.  
Habría que examinar nuevamente el uso de berilio en las prótesis 
dentales debido a su alto potencial de sensibilización.  

    Los casos de enfermedad aguda del berilio que producen 
nasofaringitis, bronquitis y neumonitis química grave han 
disminuido notablemente, y hoy en día sólo podrían producirse a 
consecuencia de errores en los sistemas de medidas de control.  La 
enfermedad crónica del berilio se diferencia de la forma aguda en 
que tiene un periodo de latencia que varía entre unas semanas y más 
de 20 años, es de larga duración y de gravedad progresiva.  
Principalmente afecta al pulmón.  La característica típica es la 
inflamación granulomatosa del pulmón asociada a disnea por esfuerzo 
excesivo, tos, dolor de pecho, pérdida de peso y debilidad general.  
Los efectos en los otros órganos pueden ser secundarios en lugar de 
sistémicos.  La gran variabilidad de la latencia y la falta de 
relación dosis-respuesta pueden observarse aún hoy en día en 
individuos sensibilizados que han estado expuestos a una 
concentración de unos 2 µg/m3.  

    Pese a algunas deficiencias en la concepción de los estudios y 
las prácticas de laboratorio, la actividad carcinogénica del 
berilio en diferentes especies animales ha sido confirmada.  

    Varios estudios epidemiológicos han demostrado que existe un 
riesgo excesivo de cáncer del pulmón debido a la exposición 
ocupacional al berilio.  Pese a las críticas sobre la 
interpretación de estos resultados, con los datos disponibles se 
llega a la conclusión de que el berilio es la explicación única más 
probable del exceso de cáncer del pulmón en los trabajadores 

9.2 Efectos en el medio ambiente

    Los datos sobre la suerte que corre el berilio en el medio 
ambiente, incluso sus efectos en organismos acuáticos y terrestres, 
son limitados.  La concentración de berilio en las aguas 
superficiales (orden de g/litro) y los suelos (orden de mg/kg de 
peso seco) es generalmente pequeña y es probable que no afecte 
negativamente al medio ambiente.  

    See Also:
       Toxicological Abbreviations
       Beryllium (HSG 44, 1990)
       Beryllium (ICSC)
       Beryllium (UKPID)