UKPID MONOGRAPH
BERYLLIUM
SM Bradberry BSc MB MRCP
ST Beer BSc
JA Vale MD FRCP FRCPE FRCPG FFOM
National Poisons Information Service
(Birmingham Centre),
West Midlands Poisons Unit,
City Hospital NHS Trust,
Dudley Road,
Birmingham
B18 7QH
This monograph has been produced by staff of a National Poisons
Information Service Centre in the United Kingdom. The work was
commissioned and funded by the UK Departments of Health, and was
designed as a source of detailed information for use by poisons
information centres.
Peer review group: Directors of the UK National Poisons Information
Service.
BERYLLIUM
Toxbase summary
Type of product
Used in nuclear reactors, electrical insulators and resistors, spark
plugs, microwave tubes, the aerospace industry, photographic equipment
and many tools.
Toxicity
The lung is the main target organ of beryllium toxicity.
Beryllium lung disease is classified as acute or chronic dependant on
the duration of disease rather than the duration of exposure. The
acute illness does not persist beyond one year.
Chronic beryllium disease is a cell-mediated (delayed)
hypersensitivity reaction characterized by granuloma formation and
pulmonary fibrosis which may be fatal.
Features
Topical
- Beryllium compounds may cause contact dermatitis.
- Beryllium ulcers occur where a beryllium crystal penetrates
the skin at a site of previous trauma.
- Beryllium chloride, fluoride, nitrate or sulphate are acute
eye irritants.
Ingestion
- Gastrointestinal beryllium absorption is poor and systemic
toxicity via this route does not occur.
Inhalation
Mild inhalation:
- Metallic taste, cough, breathlessness.
Substantial inhalation:
- Cough, chest pain, metallic taste, exertional
breathlessness, nasopharyngitis, tracheobronchitis,
conjunctivitis, pneumonitis, epistaxis and fever.
- Additional features seen in chronic beryllium disease
include fever, anorexia, arthralgia, nausea, vomiting,
haemoptysis, palpitation, convulsions, renal calculi,
corneal calcification, hepatosplenomegaly (secondary to cor
pulmonale) and systemic granulomas causing lymphadenopathy
and parotid gland enlargement.
- Chest X-ray may show upper zone nodules and fibrosis and
there may be a restrictive ventilatory defect.
Management
Topical
- Skin nodules from subcutaneous implantation of beryllium
metal or its salts are best managed by local excision.
Ingestion
- Beryllium salt ingestion is not a significant toxicological
problem.
1. Management is entirely supportive.
2. Gastrointestinal decontamination is not necessary.
Inhalation
- Most cases are occupational.
1. Occupational hygiene is paramount.
2. If pulmonary toxicity is suspected remove from exposure.
3. Symptoms of acute and chronic beryllium disease respond well to
oral steroids.
4. Experimental studies to assess the value of chelators in
beryllium poisoning are underway, but there are insufficient data
currently to recommend their use in man.Urine beryllium
concentrations allow assessment of beryllium absorption but
chronic beryllium disease is not excluded by a low urine
beryllium concentration.
References
Haberman AL, Pratt M, Storrs FJ.
Contact dermatitis from beryllium in dental alloys.
Contact Dermatitis 1993: 28: 157-62.
Hooper WF.
Acute beryllium lung disease.
N C Med J 1981; 42: 551-3.
Izumi T, Kobara Y, Inui S, Tokunaga R, Orita Y, Kitano M, Jones
Willams W.
The first seven cases of chronic beryllium disease in ceramic factory
workers in Japan.
Ann NY Acad Sci 1976 ; 278: 636-53.
Jones Williams W.
Diagnostic criteria for chronic beryllium disease (CBD) based on the
UK Registry 1945-1991.
Sarcoidosis 1993; 10: 41-3.
Kriebel D, Brain JD, Sprince NL, Kazemi H.
The pulmonary toxicity of beryllium.
Am Rev Respir Dis 1988; 137: 464-73.
Monie RDH, Roberts GH.
Chronic beryllium pneumonitis: First case accepted by UK register from
Scotland.
Scott Med J 1991; 36: 185-6.
Substance name
Beryllium
Origin of substance
Occurs in the minerals beryl, phenacite, bertrandite, bromellite
and chrysoberyl. (DOSE, 1992)
Synonyms
Beryllium-9
Glucinium (CSDS, 1989)
Chemical group
A group II A element
Reference numbers
CAS 7740-41-7 (CSDS, 1989)
RTECS DS1750000 (RTECS, 1996)
UN 1567 (Be powder) (CSDS, 1989)
HAZCHEM CODE NIF
Physicochemical properties
Chemical structure
Beryllium, Be (DOSE, 1992)
Molecular weight
9.01 (DOSE, 1992)
Physical state at room temperature
Solid (CSDS, 1989)
Colour
Greyish-white (CSDS, 1989)
Odour
Odourless (HSDB, 1996)
Viscosity
NA
pH
NA
Solubility
Insoluble in cold water (or mercury), slightly soluble in hot
water. Soluble in dilute acids and alkalis.
(HSDB, 1996)
Autoignition temperature
NIF
Chemical interactions
Beryllium reacts readily with some strong acids, producing
hydrogen. (NFPA, 1996)
Powdered beryllium mixed with carbon tetrachloride or
trichloroethylene will flash on heavy impact.
(HSDB, 1996)
Warm beryllium incandesces in fluorine or chlorine.
(HSDB, 1996)
Molten lithium at 180°C will attack beryllium severely.
(NFPA, 1996)
Major products of combustion
Combustion yields beryllium oxide fume which is toxic if inhaled.
(HSDB, 1996)
Explosive limits
NIF
Flammability
Flammable (HSDB, 1996)
Boiling point
2970°C (CSDS, 1989)
Density
1.85 at 20°C (CSDS, 1989)
Vapour pressure
NIF
Relative vapour density
NA
Flash point
NA
Reactivity
NIF
Uses
Beryllium is an important component of nuclear reactors as a
neutron source with low neutron-absorbing capacity.
Beryllium oxide is used in the electronics industry in
insulators, resistors, spark plugs and microwave tubes.
Beryllium-copper alloys are used in the aerospace, electronic,
mechanical and other industries as constituents of aircraft
engine parts, switches, circuit breakers, fuse clips, springs,
bearings, gear parts, camera shutters and many tools and are the
major source os occupational beryllium exposure.
Other important beryllium alloys are beryllium-aluminium,
beryllium-copper-cobalt and beryllium-nickel alloys.
(IPCS, 1990; Jones Williams, 1994)
Hazard/risk classification
Index no. 004-001-00-7
Risk phrases
Carc. Cat.2; R49 - May cause cancer by inhalation.
T+; R26 - Very toxic by inhalation.
T; R25-48/23 - Also toxic if swallowed. Toxic: danger of serious
damage to health by prolonged exposure through inhalation.
Xi; R36/37/38 - Irritating to eyes, respiratory system and skin.
R43 - May cause sensitization by skin contact.
Safety phrases
S53-45 - Avoid exposure - obtain special instruction before use.
In case of accident or if you feel unwell, seek medical advice
immediately (show label were possible).
EEC no. (CHIP2, 1994)
INTRODUCTION
Beryllium is a brittle metal which forms compounds in the divalent
state. It has a high affinity for oxygen such that a surface film of
beryllium oxide forms when the metal is exposed to air. This provides
resistance to corrosion which, with low density and high electrical
and thermal conductivity, make beryllium an important constituent of
many alloys; approximately 72 per cent of all beryllium produced is
used in this way (IPCS, 1990).
In the general population tobacco smoking is a major source of
beryllium exposure but beryllium toxicity is predominantly an
occupational disease via exposure to beryllium dust or fumes in the
industries listed above. Historically beryllium poisoning occurred
also during the production of fluorescent and neon lamps when
beryllium was used to coat their inner surface. In these circumstances
secondary cases of occupational beryllium poisoning occurred in the
families of workers via dust carried home in clothing (Hardy, 1965).
Non-occupational beryllium contact-sensitivity has been reported in
individuals fitted with beryllium-containing dental prostheses.
Table 1 lists the main beryllium salts by solubility.
Table 1. Solubility1 of beryllium compounds
Soluble beryllium compounds Insoluble beryllium compounds
Beryllium chloride Beryllium acetate
Beryllium fluoride Beryllium hydroxide
Beryllium nitrate Beryllium oxide
Beryllium sulphate tetrahydrate2 Beryllium sulphate
(after IPCS, 1990)
1 In cold water
2 Formed from beryllium sulphate in hot water
MECHANISM OF TOXICITY
Beryllium has been shown experimentally to disrupt phosphate and
nucleic acid metabolism with subsequent inhibition of enzyme activity
and cell replication (IPCS, 1990). Beryllium also impairs
reticuloendothelial cell function (Dinsdale et al, 1981).
As discussed below beryllium is immunogenic and capable of initiating
a type IV hypersensitivity reaction (Vilaplana et al, 1992) via
mechanisms which are, at least in part, genetically determined (Barna
et al, 1984; McConnochie et al, 1988).
TOXICOKINETICS
Absorption
Beryllium is absorbed mainly by inhalation of dust or fumes; dermal
and gastrointestinal absorption are poor. The rate of beryllium
absorption from the alveolar space depends on the solubility and
particle size of the salt with greater absorption of small particles
of soluble salts (IPCS, 1990).
Distribution
Beryllium is transported in blood and lymph protein-bound or as
colloidal beryllium phosphate (Aller, 1990). The small amount of
beryllium absorbed following ingestion is deposited primarily in bone.
By contrast, the distribution of beryllium following inhalation
depends on the solubility of the salt. Beryllium oxide, which is
poorly soluble (Table 1), is stored mainly in lung tissue, pulmonary
lymph nodes and bone whereas more soluble beryllium compounds (e.g.
beryllium chloride; Table 1) will also be found in the liver,
abdominal lymph nodes, spleen, muscle, kidney, skin and heart (IPCS,
1990).
Beryllium is taken up by cellular lysosomes and may be found
subsequently in the nucleus, nucleolus and cytoplasm (Aller, 1990).
Excretion
Lung clearance of inhaled beryllium is usually rapid during the first
few days after exposure, followed by a second slower phase (IPCS,
1990). The initial rapid elimination is explained partly by
mucociliary clearance of particulate matter with subsequent
gastrointestinal elimination and partly by beryllium uptake by
alveolar macrophages. The slow phase may be contributed to by
precipitation to a more insoluble form and embedding in pulmonary
tissues (Aller, 1990).
Beryllium which reaches the systemic circulation is eliminated mainly
in the urine, probably via active tubular secretion since most plasma
beryllium is colloidally bound and therefore does not pass through the
glomerulus (Reeves, 1986). The total body half-life of beryllium in
man is approximately 180 days (ICRP, 1960).
CLINICAL FEATURES: ACUTE EXPOSURE
Dermal exposure
Beryllium compounds may cause contact dermatitis. The beryllium source
is usually occupational although non-occupational hypersensitivity has
occurred in individuals wearing beryllium-containing dental prostheses
(Haberman et al, 1993). There is usually a latent period of one to two
weeks before the development of erythematous, macular, sometimes
blistering lesions which resolve when exposure ceases. Once
sensitization has occurred reactivation of the inflammatory response
requires only minimal beryllium contact and in this respect beryllium
skin disease is a chronic condition (VanOrdstrand et al, 1945)
although beryllium contact sensitivity is not usually associated with
systemic toxicity (Haberman et al, 1993). Beryllium ulcers occur where
a beryllium crystal penetrates the skin at a site of previous trauma
(VanOrdstrand et al, 1945; Jones Williams, 1988). Treatment by
excision and curettage usually promotes complete healing (VanOrdstrand
et al, 1945).
Ocular exposure
Dust of beryllium chloride, fluoride, nitrate and sulphate are acute
eye irritants (Grant and Schuman, 1993).
Inhalation
This may follow the inhalation of beryllium fluoride, -sulphate, -
oxide, -hydroxide or beryllium metal dust (Eisenbud et al, 1948).
Clinical features are dose-related and usually occur within days but
can be delayed for several weeks. Beryllium lung disease manifests in
acute and chronic forms, classified depending on the duration of
disease rather than the duration of exposure. Acute beryllium lung
disease is a true chemical pneumonitis which may occur during
beryllium extraction processes. It is now largely of historical
interest due to improved occupational working conditions (Markham,
1996).
Pulmonary toxicity
A single beryllium salt inhalation may cause irritation of the nose,
pharynx and eyes. Depending on the magnitude of exposure there may be
a nasal discharge and mild epistaxis (Jones Williams, 1994). More
substantial inhalation of soluble bismuth salts (Table 1) will result
in rhinitis, tracheitis and bronchitis (Jones Williams, 1994). By
contrast, less soluble beryllium salts can reach the alveoli and
moderate to severe exposure may precipitate a chemical pneumonitis,
usually within 72 hours, with cough, chest pain, exertional
breathlessness and possibly fever, hypoxia and inspiratory crackles on
auscultation of the lung fields (Kriebel et al, 1988a; Jones Williams,
1994). A subacute presentation is also recognised with more gradual
onset of respiratory symptoms, often accompanied by constitutional
upset and progression to chronic beryllium lung disease.
In patients who develop moderate or severe respiratory symptoms, chest
radiographic findings typically lag behind clinical signs for up to
three weeks (Jones Williams, 1994). In those with pneumonitis initial
diffuse shadowing may progress to widespread, poorly defined opacities
which take months to clear (Jones Williams, 1994). There are no
characteristic histological features. Restrictive spirometry may be
present but usually resolves along with radiological improvement
(Hooper, 1981).
Most patients recover from acute beryllium lung disease when removed
from exposure but fatalities have occurred (VanOrdstrand et al, 1945)
and a minority develop late complications including chronic
bronchitis, bronchiectasis, emphysema, asthma or progression to
chronic beryllium lung disease (Rees, 1979; Jones Williams, 1993). The
latter may occur after a symptom free interval of several years
(Hardy, 1965; IPCS, 1990).
Gastrointestinal toxicity
Following acute beryllium inhalation some patients complain of a
metallic taste, usually in association with symptoms of constitutional
upset including anorexia and fatigue (VanOrdstrand et al, 1945).
Diarrhoea has also been reported (Hooper, 1981).
CLINICAL FEATURES: CHRONIC EXPOSURE
Dermal exposure
Beryllium exposure from soil on abraded skin of bare feet has been
implicated in the aetiology of non-filarial elephantiasis in Ethiopia
(Frommel et al, 1993).
Inhalation
Chronic beryllium disease is a hypersensitivity response to beryllium
which occurs in susceptible individuals. There may be a latent period
of several weeks or years between exposure (which may have been only a
few hours) and the onset of symptoms. Inhalation of poorly soluble or
insoluble beryllium compounds (e.g. beryllium oxide; Table 1) or
beryllium dust are usually responsible and cases have been reported in
fluorescent lamp plants (now historical) (Hardy and Tabershaw, 1946),
ceramic factories (Izumi et al, 1976), the electronics and atomic
energy industries (Jones Willliams, 1988), those involved in the
refining of beryllium or its alloys (Cullen et al, 1987), welders
(Monie and Roberts, 1991) or manufacturers of beryllium-containing
dental prostheses (Kotloff et al, 1993).
Although the lungs are the main target organ in chronic beryllium
disease, unlike the acute illness, there are frequently widespread
systemic manifestations, many secondary to granuloma formation as
discussed below.
Pulmonary toxicity
Chronic beryllium disease manifests primarily as pneumonitis with
exertional dyspnoea, cough (which may be productive), chest pain
(Stoeckle et al, 1969; Hasan and Kazemi, 1974; Monie and Roberts,
1991) and possibly fever, haemoptysis, wheeze and hoarseness (Hasan
and Kazemi, 1974). Respiratory symptoms are frequently accompanied by
systemic upset with general malaise, anorexia and weight loss (see
below).
The most frequently observed clinical signs in the respiratory system
are finger clubbing, central cyanosis and inspiratory crackles on
auscultation of the lung fields (Stoeckle et al, 1969; Hasan and
Kazemi, 1974; Monie and Roberts, 1991; Jones Williams, 1994).
Death has occurred following massive haemoptysis in a patient with
bilateral upper lobe mycetomas (probably related to steroid therapy)
(O'Brien et al, 1987).
In chronic beryllium disease a diffuse reticular pattern, more
prominent in the upper zones, is seen on chest x-ray with nodules of
varying size and sometimes bilateral (possibly calcified) hilar
adenopathy (Andrews et al, 1969; Stoeckle et al, 1969; Hasan and
Kazemi, 1974). There may be progression to upper zone fibrosis with
relative emphysema in adjacent lobes, pleural thickening,
pneumothoraces (usually from ruptured bullae) and evidence of
pulmonary hypertension (Stoeckle et al, 1969; Hasan and Kazemi, 1974).
Pulmonary function tests typically show a restrictive, or isolated
diffusion defect, but obstructive lesions have been reported (Andrews
et al, 1969). A probable "dose-related" decrease in FVC and FEV1
without chest x-ray abnormalities has also been described (Kriebel et
al, 1988b).
Lung biopsy in chronic beryllium disease usually shows a chronic
inflammatory response with non-caseating granulomas, diffuse fibrosis
and smooth muscle hypertrophy (Andrews et al, 1969; Hasan and Kazemi,
1974). The presence of beryllium in tissue sections can be confirmed
using laser microprobe mass spectrometry (LAMMS) analysis (Jones
Williams and Wallach, 1989; Monie and Roberts, 1991).
In 124 cases of chronic beryllium disease, Freiman and Hardy (1970)
found a clear relation between the histological appearance of the lung
(at lung biopsy or autopsy) and disease prognosis. Only 26 of 95
patients with histological evidence of diffuse pulmonary cell
infiltration were alive at the time of the study with a mean disease
duration of 8.3 years for the entire group. Follow-up of 43 patients
in the UK Beryllium Case Registry 1945-91 (Jones Williams, 1993)
reported 25 deaths, 21 from cor pulmonale, though nearly half had
survived more than 20 years from the original diagnosis.
Lung damage in chronic beryllium disease may be partly reversible. In
a survey of 214 workers at a beryllium plant Sprince et al (1978)
demonstrated that beryllium-induced hypoxemia and radiographic
abnormalities were reduced over three years following improved
workplace ventilation and engineering processes with a significant
reduction in the air beryllium concentration.
Chronic beryllium disease reflects a cell-mediated (delayed)
hypersensitivity reaction as evidenced by the ability of beryllium to
activate proliferation of beryllium-specific helper T cells (Deodhar
et al, 1973). This property forms the basis of the lymphocyte
transformation test (LTT) which was shown by Rossman et al (1988) to
have high sensitivity and specificity in the diagnosis of chronic
beryllium disease using bronchoalveolar lavage fluid cells. In
patients with compatible lung pathology Mroz et al (1991) found that
an abnormal LTT in peripheral blood cells also could diagnose chronic
beryllium disease reliably.
The current diagnostic criteria for chronic beryllium disease
therefore are a positive blood beryllium lymphocyte transformation
test in the presence of a history of beryllium exposure, consistent
clinical and radiological features plus granulomas and beryllium
deposits in tissues (Jones Williams, 1988).
It should be remembered that a positive beryllium LTT alone is not
diagnostic of chronic beryllium disease; it reflects beryllium
exposure but may be reversible when exposure is reduced (Rom et al,
1983).
Reports that chronic beryllium disease shows a familial tendency
probably reflect the role of histocompatibility antigens in beryllium
hypersensitivity (McConnochie et al, 1988; Saltini et al, 1989;
Deodhar and Barna 1991). It is also likely that the observed
precipitation of chronic beryllium disease by pregnancy or infection
(Hardy and Tabershaw, 1946) is related to altered immunological
status.
The main differential diagnosis in chronic beryllium disease is
sarcoidosis although the presence of beryllium in tissues and a
positive beryllium lymphocyte transformation test allow clarification
(Jones Williams and Wallach, 1989). The Kveim test is negative in
beryllium disease (Jones Williams and Wallach, 1989).
Dermal toxicity
Chronic pulmonary beryllium toxicity may be complicated by cutaneous
granulomas (Jones Williams, 1994).
Gastrointestinal toxicity
Patients with chronic beryllium disease often experience anorexia,
weight loss, nausea and vomiting (Hasan and Kazemi, 1974; Jones
Williams, 1994). Parotid gland enlargement is due to granuloma
formation (Hasan and Kazemi, 1974).
Nephrotoxicity
Hypercalciuria is common in chronic beryllium disease and renal
calculi have been reported (Hardy and Tabershaw, 1946; Stoeckle et al,
1969). Granulomata may be seen on renal biopsy (Jones Williams, 1994)
Cardiovascular toxicity
Patients with severe untreated chronic beryllium lung disease may
develop cor pulmonale with orthopneoa, palpitation (Hasan and Kazemi,
1974), hepatomegaly and/or splenomegaly (Hall et al, 1959; Stoeckle et
al, 1969; Jones Williams, 1993).
Neurotoxicity
Central nervous system granulomas may cause seizures (Hasan and
Kazemi, 1974).
Haemotoxicity
Extrapulmonary lymph node granulomata may cause generalised
lymphadenopathy (Hasan and Kazemi, 1974). Granulomas may be found also
in the spleen and bone marrow (Stoeckle et al, 1969; Jones Williams,
1994).
Musculoskeletal toxicity
Arthralgia may be a feature of chronic beryllium disease (Hasan and
Kazemi, 1974).
Ocular toxicity
Corneal calcification and band keratopathy have been described in
chronic beryllium disease (Grant and Schuman, 1993). A positive
Schirmer's test (indicating reduced tear secretion) is recognized
(McConnochie et al, 1988; Monie and Roberts, 1991).
MANAGEMENT
Dermal exposure
Skin nodules developing from subcutaneous implantation of beryllium
metal alloy or its salts, particularly in machinists and ceramic
workers with skin lacerations, are best managed by local excision.
This is usually curative although chronic beryllium disease has
developed in isolated cases (Jones Williams, 1988).
Inhalation
Occupational hygiene
Beryllium toxicity is only likely to occur following occupational
exposure, usually by inhalation of beryllium containing dusts or
powders. In these circumstances cessation of exposure is the priority.
Adequate skin protection and hygiene to avoid unnecessary beryllium
exposure are essential.
Supportive measures
Symptoms of acute and chronic beryllium disease respond well to oral
prednisolone (20-80 mg daily) and in the chronic form treatment is
usually lifelong (Izumi et al, 1976; Jones Williams, 1994).
Antidotes
DMPS and DMSA
In animal studies oral DMPS or DMSA (50 mg/kg bd for five days)
increased faecal but not urinary beryllium excretion in rats
administered 0.5 mg/kg intraperitoneal beryllium nitrate daily for
five days/week for three weeks (Flora et al, 1995). Chelation therapy
with both agents reversed the hepatotoxic effect of beryllium as shown
by liver alkaline phosphatase activity and DMPS caused a significant
reduction in the liver and spleen beryllium content in association
with an increased blood beryllium concentration (Flora et al, 1995).
There are no data regarding the use of DMPS or DMSA in human beryllium
poisoning.
HEDTA and EDTA
In beryllium-poisoned rats (treated for 18 days with parenteral
beryllium nitrate 1 mg/kg daily) the administration of intraperitoneal
HEDTA (N-(2-hydroxyethyl)ethylenediamine triacetic acid) or calcium
disodium EDTA (ethylenediamine tetraacetic acid) prevented
beryllium-induced hepatotoxicity (as indicated by hepatic alkaline
phosphatase activity) but neither chelating agent significantly
reduced blood or tissue beryllium concentrations (Mathur et al, 1993).
Iron
In animal studies intraperitoneal ferric ammonium citrate (40 mg/kg
body weight daily) commenced three days prior to beryllium exposure
and continued until death or recovery, protected against
beryllium-induced mortality in rats exposed to intravenous beryllium
sulphate (6 mg/kg). (Lindenschmidt et al, 1986) or an aerosol of
beryllium sulphate (30 per cent w/v) (Sendelbach and Witschi, 1987)
via increased ferritin production with subsequent faecal elimination
of ferritin-bound beryllium. There are no human data regarding iron
therapy in the management of beryllium poisoning.
MEDICAL SURVEILLANCE
Health surveillance is necessary for those potentially exposed to
beryllium fumes or dust. Pre-employment clinical examination and chest
x-ray are recommended. Those with an history of atopy are particularly
susceptible to beryllium lung disease (Hooper, 1981). Regular
monitoring of the beryllium concentration in workplace air, with
provision of protective respiratory equipment if required, is
mandatory (Health and Safety Executive, 1994).
Urine beryllium concentrations allow assessment of beryllium
absorption (Health and Safety Executive, 1994) but chronic beryllium
disease is not excluded by a low urine beryllium concentration (IPCS,
1990).
The identification of beryllium in affected tissues remains important
in establishing the diagnosis (Jones Williams and Wallach, 1989; Jones
Williams, 1994). Kreiss et al (1989) demonstrated that subclinical
chronic beryllium disease could be detected via a positive lymphocyte
proliferation test but recent studies suggest this has a limited role
in screening (Stokes and Rossman, 1991).
Since there may be a substantial latency period between beryllium
exposure and the onset of beryllium disease, retired workers should be
kept under medical supervision for up to 20 years.
The UK Beryllium Case Registry provides important information on the
incidence and clinical course of beryllium disease (Jones Williams et
al, 1980). By 1994 it included 59 cases of whom 47 manifest the
chronic form (Jones Williams, 1994).
OCCUPATIONAL DATA
Maximum exposure limit
Long-term exposure limit (8 hour TWA reference period)
0.002 mg/m3 (Health and Safety Executive, 1995b).
OTHER TOXICOLOGICAL DATA
Carcinogenicity
In a cohort mortality study of 689 patients included in a North
American beryllium disease case registry mortality from lung cancer
(standardised mortality ratio (SMR) = 2.0) and non malignant beryllium
disease were significantly increased, with deaths from lung cancer
occurring more frequently in those with acute rather than chronic
beryllium disease (Steenland and Ward, 1991).
Ward et al (1992) similarly found a significantly increased SMR for
lung cancer in workers at two beryllium plants in operation before
1950 although the overall slightly increased SMR for the 9225 cohort
of workers from seven plants was not significant.
The International Agency for Research on Cancer (IARC) Working Group
on the carcinogenicity of beryllium has concluded that there is
"sufficient evidence in humans for the carcinogenicity of beryllium
and beryllium compounds" (IARC, 1993) although their conclusions have
been disputed (MacMahon, 1994; Kotin, 1994a and b).
By 1993 there were no known cases of beryllium-associated lung cancer
in the UK registry (Jones Williams, 1993).
Reprotoxicity
There are no data confirming that beryllium is a reprotoxin in man
(Reprotox, 1996).
Genotoxicity
Escherichia coli, HeLa cells and Ehrlich ascites tumour cells, DNA
cell binding assays positive
Chinese hamster ovary and rat lung epithelial cells, 20 hr exposure,
positive cytotoxic effects
Oral rat (6 month) in drinking water, caused cytotoxicity at the toxic
dose level and induced chromosomal aberrations, but was negative in
dominant lethal assays (DOSE, 1992).
Fish toxicity
Acute toxicity range to fish (24-96 hr) (species unspecified) in fresh
water 87-0.97 µg/L
LC50 (96 hr) fathead minnow 150 µg/L (DOSE, 1992).
EC Directive on Drinking Water Quality 80/778/EEC
NIF
AUTHORS
SM Bradberry BSc MB MRCP
ST Beer BSc
JA Vale MD FRCP FRCPE FRCPG FFOM
National Poisons Information Service (Birmingham Centre),
West Midlands Poisons Unit,
City Hospital NHS Trust,
Dudley Road,
Birmingham
B18 7QH
UK
This monograph was produced by the staff of the Birmingham Centre of
the National Poisons Information Service in the United Kingdom. The
work was commissioned and funded by the UK Departments of Health, and
was designed as a source of detailed information for use by poisons
information centres.
Date of last revision
16/7/96
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