Beryllium poisoning
Encyclopedia
Beryllium poisoning refers to the toxic effects of beryllium
Beryllium
Beryllium is the chemical element with the symbol Be and atomic number 4. It is a divalent element which occurs naturally only in combination with other elements in minerals. Notable gemstones which contain beryllium include beryl and chrysoberyl...

, in its elemental form or in various chemical compounds. The toxicity of beryllium depends upon the duration, intensity and frequency of exposure (features of dose), as well as the form of beryllium and the route of exposure (i.e. inhalation, dermal, ingestion). According to the International Agency for Research on Cancer
International Agency for Research on Cancer
The International Agency for Research on Cancer is an intergovernmental agency forming part of the World Health Organisation of the United Nations....

 (IARC), beryllium and beryllium compounds are Category 1 carcinogens; they are carcinogenic to both animals and humans.

Chronic berylliosis
Berylliosis
Berylliosis, or chronic beryllium disease , is a chronic allergic-type lung response and chronic lung disease caused by exposure to beryllium and its compounds. As an occupational lung disease, it is most classically associated with beryllium mining or manufacturing of fluorescent light bulbs...

 is a pulmonary and systemic
Systemic circulation
Systemic circulation is the part of the cardiovascular system which carries oxygenated blood away from the heart to the body, and returns deoxygenated blood back to the heart. This physiologic theory of circulation was first described by William Harvey...

 granulomatous disease caused by exposure to beryllium. Acute beryllium disease in the form of chemical pneumonitis
Chemical pneumonitis
Aspiration pneumonitis or chemical pneumonitis is inflammation of the lung caused by aspirating or inhaling irritants. It is sometimes called a "chemical pneumonia", though it is not infectious...

 was first reported in Europe in 1933 and in the United States in 1943. Cases of chronic berylliosis were first described in 1946 among workers in plants manufacturing fluorescent lamp
Fluorescent lamp
A fluorescent lamp or fluorescent tube is a gas-discharge lamp that uses electricity to excite mercury vapor. The excited mercury atoms produce short-wave ultraviolet light that then causes a phosphor to fluoresce, producing visible light. A fluorescent lamp converts electrical power into useful...

s in Salem, Massachusetts
Salem, Massachusetts
Salem is a city in Essex County, Massachusetts, United States. The population was 40,407 at the 2000 census. It and Lawrence are the county seats of Essex County...

. Chronic berylliosis resembles sarcoidosis
Sarcoidosis
Sarcoidosis , also called sarcoid, Besnier-Boeck disease or Besnier-Boeck-Schaumann disease, is a disease in which abnormal collections of chronic inflammatory cells form as nodules in multiple organs. The cause of sarcoidosis is unknown...

 in many respects, and the differential diagnosis
Differential diagnosis
A differential diagnosis is a systematic diagnostic method used to identify the presence of an entity where multiple alternatives are possible , and may also refer to any of the included candidate alternatives A differential diagnosis (sometimes abbreviated DDx, ddx, DD, D/Dx, or ΔΔ) is a...

 is often difficult. It occasionally killed early workers in nuclear weapons design, such as Herbert L. Anderson
Herbert L. Anderson
Herbert Lawrence Anderson was an American nuclear physicist who contributed to the Manhattan Project. He was also a member of the team which made the first demonstration of nuclear fission in the United States, in the basement of Pupin Hall at Columbia University. He participated in the first...

.

Although the use of beryllium compounds in fluorescent lighting tubes was discontinued in 1949, potential for exposure to beryllium exists in the nuclear and aerospace industries and in the refining of beryllium metal and melting of beryllium-containing alloys, the manufacturing of electronic devices, and the handling of other beryllium-containing material.

Early researchers tasted beryllium and its various compounds for sweetness in order to verify its presence. Modern diagnostic equipment no longer necessitates this highly risky procedure and no attempt should be made to ingest this highly toxic substance. Beryllium and its compounds should be handled with great care and special precautions must be taken when carrying out any activity which could result in the release of beryllium dust (lung cancer
Lung cancer
Lung cancer is a disease characterized by uncontrolled cell growth in tissues of the lung. If left untreated, this growth can spread beyond the lung in a process called metastasis into nearby tissue and, eventually, into other parts of the body. Most cancers that start in lung, known as primary...

 is a possible result of prolonged exposure to beryllium laden dust).

This substance can be handled safely if certain procedures are followed. No attempt should be made to work with beryllium before familiarization with correct handling procedures.

A successful test for beryllium in air and on surfaces has been recently developed and published as an international voluntary consensus standard (ASTM D7202; www.astm.org). The procedure uses dilute ammonium bifluoride for dissolution and fluorescence detection with beryllium bound to sulfonated hydroxybenzoquinoline, allowing detection up to 100 times lower than the recommended limit for beryllium concentration in the workplace. Fluorescence increases with increasing beryllium concentration. The new procedure has been successfully tested on a variety of surfaces and is effective for the dissolution and ultratrace detection of refractory beryllium oxide and siliceous beryllium (ASTM D7458).

Inhalation

Beryllium is harmful if inhaled and the effects depend on the duration, intensity, and frequency of exposure. If beryllium concentrations in air are high enough (greater than ), an acute condition can result, called acute beryllium disease, which resembles pneumonia
Pneumonia
Pneumonia is an inflammatory condition of the lung—especially affecting the microscopic air sacs —associated with fever, chest symptoms, and a lack of air space on a chest X-ray. Pneumonia is typically caused by an infection but there are a number of other causes...

. Occupational and community air standards are effective in preventing most acute lung damage. Long-term beryllium exposure can increase the risk of developing lung cancer
Lung cancer
Lung cancer is a disease characterized by uncontrolled cell growth in tissues of the lung. If left untreated, this growth can spread beyond the lung in a process called metastasis into nearby tissue and, eventually, into other parts of the body. Most cancers that start in lung, known as primary...

.

The more common serious health problem from beryllium today is chronic beryllium disease (CBD), discussed below. It continues to occur in industries as diverse as metal recycling, dental laboratories, alloy manufacturing, nuclear weapons production and metal machine shops that work with alloys containing small amounts of beryllium. A 2005 study found that "Both CBD and sensitization occurred in former workers whose mean daily working lifetime average exposures were lower than the current allowable Occupational Safety and Health Administration workplace air level of 2 μg/m3 and the Department of Energy guideline of 0.2 μg/m3." A 2008 report from the United States National Research Council
United States National Research Council
The National Research Council of the USA is the working arm of the United States National Academies, carrying out most of the studies done in their names.The National Academies include:* National Academy of Sciences...

 said that worker exposure to beryllium should be kept "at the lowest feasible level," as the agency's research could not establish any safe level of exposure.

Acute Beryllium Disease

Overexposure to beryllium can cause inflammation of the upper and/or lower respiratory tracts. The symptoms of acute beryllium disease are non-specific, resembling other inhalational injuries, viral infections, or pneumonia. Upper respiratory findings include nasopharyngitis and tracheobronchitis. Symptoms may include irritation of the nares and pharynx
Pharynx
The human pharynx is the part of the throat situated immediately posterior to the mouth and nasal cavity, and anterior to the esophagus and larynx. The human pharynx is conventionally divided into three sections: the nasopharynx , the oropharynx , and the laryngopharynx...

, epistaxis, cough, and a metallic taste. Nasopharyngitis can progress to formation of nasal fissures, ulcerations, or perforation.

Therapy is supportive and includes removal from further beryllium exposure. Acute beryllium pneumonitis produces severe cough (occasionally with blood-streaked sputum), chest pain or burning, and shortness of breath. The patient is usually ill-appearing, and presents with hypoxemia
Hypoxemia
Hypoxemia is generally defined as decreased partial pressure of oxygen in blood, sometimes specifically as less than or causing hemoglobin oxygen saturation of less than 90%.-Distinction from anemia and hypoxia:...

, cyanosis
Cyanosis
Cyanosis is the appearance of a blue or purple coloration of the skin or mucous membranes due to the tissues near the skin surface being low on oxygen. The onset of cyanosis is 2.5 g/dL of deoxyhemoglobin. The bluish color is more readily apparent in those with high hemoglobin counts than it is...

, tachycardia
Tachycardia
Tachycardia comes from the Greek words tachys and kardia . Tachycardia typically refers to a heart rate that exceeds the normal range for a resting heart rate...

, and shallow rapid breathing. Systemic symptoms include fever (usually low-grade), malaise, and anorexia. The chest X-ray can reveal diffuse, bilateral alveolar infiltrates.

There is no specific diagnostic test for acute beryllium disease. Biopsy of the lungs reveals a nonspecific granulomatous inflammation. Treatment is supportive, including oxygen supplementation as needed, and removal from further beryllium exposure. Corticosteroids are sometimes tried, but no good controlled studies are reported. The signs and symptoms of acute beryllium pneumonitis usually resolve over several weeks to months, but it may be fatal, and about 15–20% of cases may progress to CBD.

Chronic Beryllium Disease (CBD)

Sensitization is not an illness, but some exposed individuals, if inhaling sufficient quantities of beryllium dust in the micrometer-size range, may have an inflammatory reaction that principally targets the respiratory system and skin. This condition is called chronic beryllium disease (CBD), and can occur within a few months or many years (average 10 years in some series) after exposure to higher-than-normal levels of beryllium (greater than ). This disease causes fatigue, weakness, night sweats and can cause difficulty in breathing and a persistent dry cough. It can result in anorexia
Anorexia (symptom)
Anorexia is the decreased sensation of appetite...

, weight loss, and may also lead to right-side heart enlargement and heart disease in advanced cases.

Typically, CBD has an insidious onset and runs an indolent course. Some people who are sensitized to beryllium may not have symptoms, and just being sensitized is not a recognized health effect. CBD occurs when the body's immune system
Immune system
An immune system is a system of biological structures and processes within an organism that protects against disease by identifying and killing pathogens and tumor cells. It detects a wide variety of agents, from viruses to parasitic worms, and needs to distinguish them from the organism's own...

 recognizes beryllium particles as foreign material and mounts an immune system attack against the particles. Because these particles are typically inhaled into the lungs, the lungs become the major site where the immune system responds. The lung sacs become inflamed and fill with large numbers of white blood cells that accumulate wherever beryllium particles are found. These cells form balls around the beryllium particles called "granuloma
Granuloma
Granuloma is a medical term for a tiny collection of immune cells known as macrophages. Granulomas form when the immune system attempts to wall off substances that it perceives as foreign but is unable to eliminate. Such substances include infectious organisms such as bacteria and fungi as well as...

s." When enough of these develop, they interfere with the normal function of the organ. Over time, the lungs become stiff and lose their ability to transfer oxygen from the air into the bloodstream. Early on in the disease, there may be a mild obstructive ventilatory defect. In advanced cases, there is a restrictive defect and reduced diffusion capacity
Diffusion capacity
In biology, diffusion capacity is a measurement of the lung's ability to transfer gases. Oxygen uptake may be limited by diffusion in circumstances of low ambient oxygen or high pulmonary blood flow...

. Patients with CBD develop difficulty inhaling and exhaling sufficient amounts of air, and the amount of oxygen in their bloodstreams falls.

Most of the clinical features of CBD are indistinguishable from thoracic involvement with sarcoidosis
Sarcoidosis
Sarcoidosis , also called sarcoid, Besnier-Boeck disease or Besnier-Boeck-Schaumann disease, is a disease in which abnormal collections of chronic inflammatory cells form as nodules in multiple organs. The cause of sarcoidosis is unknown...

. The chest radiograph usually reveals bilateral, mid- and upper-lobe predominant reticulonodular infiltrates, as well as hilar and mediastinal adenopathy. For suspected cases of CBD, fiber-optic bronchoscopy
Bronchoscopy
Bronchoscopy is a technique of visualizing the inside of the airways for diagnostic and therapeutic purposes. An instrument is inserted into the airways, usually through the nose or mouth, or occasionally through a tracheostomy. This allows the practitioner to examine the patient's airways for...

 with bronchoalveolar lavage
Bronchoalveolar lavage
Bronchoalveolar lavage is a medical procedure in which a bronchoscope is passed through the mouth or nose into the lungs and fluid is squirted into a small part of the lung and then recollected for examination. BAL is typically performed to diagnose lung disease...

 (BAL) is indicated. The BAL fluid should undergo beryllium lymphocyte proliferation testing (BAL BeLPT), the "gold standard" for the diagnosis. The measurement of beryllium in urine or tissue does not establish the diagnosis, and there are technical and interpretive problems with these tests. Blood BeLPT detects approximately 70-90% of CBD cases.

CBD is treatable, but not curable with traditional drugs and medicine. Removal from further beryllium exposure is advisable. Treatment includes supplemental oxygen and corticosteroids (such as prednisone
Prednisone
Prednisone is a synthetic corticosteroid drug that is particularly effective as an immunosuppressant drug. It is used to treat certain inflammatory diseases and some types of cancer, but has significant adverse effects...

) to lower the body's overreaction to beryllium. If therapy with corticosteroid is successful, treatment is usually continued lifelong because of disease relapse after steroid cessation. In general, CBD worsens without treatment. Prognosis is best for those diagnosed at an earlier stage. Overall mortality rates are 5-38%.

The general population is unlikely to develop acute or chronic beryllium disease because ambient air levels of beryllium are normally very low (<0.03 ng/m3).

Ingestion

Swallowing beryllium has not been reported to cause effects in humans because very little beryllium is absorbed from the stomach and intestines. Harmful effects have sometimes been seen in animals ingesting beryllium.

Dermatological effects

Beryllium can cause local irritation and contact dermatitis
Contact dermatitis
Contact dermatitis is a term for a skin reaction resulting from exposure to allergens or irritants . Phototoxic dermatitis occurs when the allergen or irritant is activated by sunlight....

. Beryllium contact with skin that has been scraped or cut may cause rash
Rash
A rash is a change of the skin which affects its color, appearance or texture. A rash may be localized in one part of the body, or affect all the skin. Rashes may cause the skin to change color, itch, become warm, bumpy, chapped, dry, cracked or blistered, swell and may be painful. The causes, and...

es, ulcers, or bumps under the skin called granuloma
Granuloma
Granuloma is a medical term for a tiny collection of immune cells known as macrophages. Granulomas form when the immune system attempts to wall off substances that it perceives as foreign but is unable to eliminate. Such substances include infectious organisms such as bacteria and fungi as well as...

s. Beryllium dust or powder can irritate the eyes, producing itching, burning, or conjunctivitis
Conjunctivitis
Conjunctivitis refers to inflammation of the conjunctiva...

.

Effects on children

There are no studies on the health effects of children exposed to beryllium, although individual cases of CBD have been reported in children of beryllium workers from the 1940s. It is unknown whether children differ from adults in their susceptibility to beryllium. It is unclear whether beryllium is teratogenic.

Detection in the body

Beryllium can be measured in the urine and blood. The amount of beryllium in blood or urine may not indicate time or quantity of exposure. Beryllium levels can also be measured in lung and skin samples. While such measurements may help establish that exposure has occurred, other tests are used to determine if that exposure has resulted in health effects. A blood test, the blood beryllium lymphocyte proliferation test (BeLPT), identifies beryllium sensitization and has predictive value for CBD.

The BeLPT has become the standard test for detecting beryllium sensitization and CBD in individuals who are suspected of having CBD and to help distinguish it from similar conditions such as sarcoidosis. It is also the main test used in industry health programs to monitor whether disease is occurring among current and former workers who have been exposed to beryllium on the job. The test can detect disease that is at an early stage, or can detect disease at more advanced stages of illness as well. The BeLPT can also be performed using cells obtained from a person's lung by a procedure called "bronchoscopy".

Industrial release and occupational exposure limits

Typical levels of beryllium that industries may release into the air are of the order of , averaged over a 30-day period, or of workroom air for an 8-hour work shift. Compliance with the current U.S. Occupational Safety and Health Administration
Occupational Safety and Health Administration
The United States Occupational Safety and Health Administration is an agency of the United States Department of Labor. It was created by Congress of the United States under the Occupational Safety and Health Act, signed by President Richard M. Nixon, on December 29, 1970...

 (OSHA) permissible exposure limit
Permissible Exposure Limit
The permissible exposure limit is a legal limit in the United States for exposure of an employee to a chemical substance or physical agent. For chemicals, the chemical regulation is usually expressed in parts per million , or sometimes in milligrams per cubic metre . Units of measure for physical...

 for beryllium of has been determined to be inadequate to protect workers from developing beryllium sensitization and CBD. The American Conference of Governmental Industrial Hygienists
American Conference of Governmental Industrial Hygienists
The American Conference of Governmental Industrial Hygienists is a professional association of industrial hygienists and practitioners of related professions, with headquarters in Cincinnati, Ohio...

(ACGIH), which is an independent organization of experts in the field of occupational health, has proposed a threshold limit value (TLV) of in a 2006 Notice of Intended Change (NIC). This TLV is 40 times lower than the current OSHA permissible exposure limit, reflecting the ACGIH analysis of best available peer-reviewed research data concerning how little airborne beryllium is required to cause sensitization and CBD.

Because it can be difficult to control industrial exposures to beryllium, it is advisable to use any methods possible to reduce airborne and surface contamination by beryllium, to minimize the use of beryllium and beryllium-containing alloys whenever possible, and to educate people about the potential hazards if they are likely to encounter beryllium dust or fumes.

On 29 January 2009, the Los Alamos National Laboratory announced it was notifying nearly 2,000 current and former employees and visitors that they may have been exposed to beryllium in the lab and may be at risk of disease. Concern over possible exposure to the material was first raised in November 2008, when a box containing beryllium was received at the laboratory's short-term storage facility.
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