# CRITERIA DOCUMENT:

# RECOMMENDATIONS FOR AN OCCUPATIONAL EXPOSURE STANDARD FOR BERYLLIUM
(1) Spirometry, including FVC and F E V^q .
(2) A medical history questionnaire that includes presence and degree of respiratory symptoms, i.e., breathlessness, cough, sputum production, and wheezing.
(3) A 14" by 17" chest X-ray. (2) Workers with Minimum Beryllium Bxposure

# (i)
The employer shall provide laboratory coats or equivalen protective clothing to each such employee who works with or is exposed to beryllium, beryllium compounds, or beryllium containing products.
(ii) Clean protective clothing shall be supplied to each worker at least weekly.  (2) Showers for exposed workers shall be required following a work shift and prior to putting on street clothes.
(3) Locker-shower facilities shall be so arranged that the showers can serve to demarcate between potentially "clean" and "contaminated" areas.
(4) Suitable provisions shall be made for the control of con taminated dust in workshoe storage and clothing hamper locations.
(5) Handwashing and toilet facilities shall be arranged so that following use, workers need not re-enter a potentially contaminated area. In 1936 G e l m a n^ described illnesses among workers in beryllium plants in Moscow. He described two phases of the clinical symptoms caused *Much confusion has resulted from use of this term because of its similarity in spelling relating to beryl ore (beryllosls) and to use of the term in describing both acute and chronic manifestations of beryllium related disorders. Accordingly, the terms "beryllium disease" and "beryllium poisoning" will be used in this report.
IV-1 by exposure to vapors of beryllium oxyfluoride: the first phase, beryllium fever, was not unlike that caused by exposure to zinc oxide fumes; the second phase was described as an extensive alveobronchiolitis. Two years later he described effects on the skin and X-ray changes in the lungs.  oxides have been productive of osteogenic sarcomas in rabbits following intravenous administration and primary lung tumors in rats and monkeys following inhalation, there is no evidence that community or industrial exposure to beryllium compounds is associated with an increase in the incidence of cancer in humans."
In 1970 Mancuso,^ in an epidemiological study based upon mortality of beryllium workers, found an equal or higher rate of cancer of the lung in employees employed for a short duration (3 to 15 months) as contrasted to those employed for a longer period (18 months or longer). A higher mortality rate was also suggested among the short duration employees of one plant, but this was not supported by results from a second plant. There Based on the degree of interstitial cellular infiltration they found that 80 percent of the cases studied showed moderate to marked infiltration whereas in the remainder, cellular infiltration was only slight or absent. Clearly defined granulomatous lesions were not always present. The group with prominent interstitial cellular infiltration could be subgrouped into two groups in which granuloma formation was either

# IV-9
well formed or else poorly-formed-to-absent. Where cellular Infiltration was slight or absent, granuloma formation was numerous and well formed.
D u d l e y^ in 1959 reported that the occurence of granulomatous lesions often tended to draw attention away from the more fundamental diffuse interstitial infiltration of which the granulomas were only a part. This same reaction was also seen in skin, liver, kidney, lymph nodes, and skeletal muscle. Cardiac muscle, spleen, and pleura also could be involved.
Freiman and H a r d y^ suggest a distinct relation between the intensity of interstitial cellular infiltration and the forecast of disease severity, with the possibility that the degree of granuloma formation may play a significant secondary role. Calcific inclusions were also commonly present,
being observed in about two-thirds of the lungs from patients with chronic disease.
In addition, increased tissue levels of beryllium were noted in most cases.
Although most cases of beryllium disease can be recognized by patho logic changes,^^5,46,47 observations are not specific for the disease.
Pulmonary sarcoidosis, "farmers lung",^ fungus diseases, and various pneumoconioses are but a few disorders which also produce a similar pathologic picture. Differentiation between sarcoidosis and chronic beryllium disease is the most difficult. Similarities and differences between the two disorders have been presented for diagnostic purposes.4449 (c) Chronic Effects -Treatment: Early treatment of chronic beryllium disease was purely symptomatic with oxygen providing great relief in cases where impaired ventilation was noted. Antibiotics were only of value to treat secondary infections. Long periods of bedrest were employed.

# IV-10
Patients were occasionally transferred to warm or dry climates to provide temporary relief, but no detectable change in the course of the disease was noted. 30  Sarcoidosis presents the most troublesome problem in differential diagnosis of chronic beryllium disease. Hardy and F r e i m a n ,^^ in presenting beryllium disease as a continuing diagnostic problem, listed specific differences between beryllium disease and sarcoidosis. These differences include weight loss and severe loss of appetite, rarely seen in sarcoidosis, the presence in histopathologic sections of intense cellular infiltration with nodular lesions and abundant calcific inclusions, the absence of many characteristic localization patterns frequently seen in sarcoidosis, and the occurrence of significant amounts of beryllium in the tissues of many patients.
(i) X-ray changes were reviewed by Gary and Schatzki"*^ in a study of all available X-rays in the Beryllium Registry, and they concluded that there was not an orderly sequence of lung involvement as had been previously postulated,22,58 but rather, definite reaction types which persisted unchanged for many years. Disease which began with nodular manifestations stayed nodular. Further, they stressed that because of the several types of response seen on films, it appeared impossible to make a differential diagnosis by radiological means alone.
In 1970, Weber, Stoeckle, and Hardy,in a study of 8 cases observed for up to 18 years, reported that X-ray changes, most frequently involving the upper lobes, consisted of granular, nodular, and linear densities occurring singly and in combined forms. Mixed patterns of granular and nodular densities were most commonly seen. Persistence of granular densities alone was rarely observed. Small and scattered linear densities often developed, and in advanced cases, were very marked and associated with emphysema. Fibrotic changes confined to the lower lobes were rarely seen.
With fibrotic and emphysematous changes, granular and nodular densities diminished to a point where X-ray diagnosis was not indicated.
Chamberlin^ stated that clinical and X-ray findings alone established only presumptive diagnosis of beryllium disease. Although X-ray findings are not specific, the appearance of a known pattern of beryllium disease on a chest film should immediately alert the physician to the possibility of this diagnosis.
(ii) Tissue sensitization has been reported. Sterner and Eisenbud in 1 9 5 1^8 proposed that beryllium acts to produce allergic sensi tization in tissues.
In 1959, the patch test developed by Curtis was claimed to give favorable differentiation between chronic beryllium disease and other pulmonary diseases.^ The positive patch test did not serve as an absolute diagnostic sign for chronic beryllium disease; in fact, in cases where differential diagnosis has been difficult, the patch test has not been very helpful.^8 J e t t^ has shown an immunologic basis to chronic beryllium disease, and a hypersensitivity phenomenon has been demonstrated.
Since the skin patch test can develop a hypersensitive state in persons who have never been exposed to beryllium, its use in differential diagnosis is generally discouraged and the test is best avoided in screening persons who 28 are to be exposed to beryllium.
(ill) Tissue and fluid analysis for beryllium is used to establish previous exposure to beryllium. The detection of beryllium in tissue or urine is evidence of exposure to beryllium only, not necessarily to the presence of beryllium disease.^ Lung biopsy has been recommended as a means for positive beryllium identification.^ Frequently, negative findings of beryllium in the lungs of persons having known exposure to the material are due to inadequate sample quantities. At least a 5 gm specimen is recommended for lung tissue.^ The chances of positive analysis are accordingly reduced for other organs since they contain much less material than the lung. Beryllium is not generally considered to be a natural environmental contaminant; however, C h o l a k^ tabulated the presence of extremely small quantities in soil, coal, and air. The more rarely produced osteogenic sarcoma and rickets are peculiar to experimental animals, although the granuloma of the skin with ulcer occurs in man as well.

# IV-13
( Beryllium "rickets" is likewise a condition not seen in man, probably because the rickets were produced in young animals on diets with substantial amounts of BeCO^ (0.5 and 2%),^ conditions not met in the human situation.
A toxic macrocytic anemia that has been reported to result in animals exposed by inhalation to beryllium compounds and substantiated by demonor strated interference in both heme and globin synthesis seems not to have been noted in individuals with beryllium disease.

# IV-16
Finally, the morphologic changes in the lungs of animals with alveolar metaplasia, do not resemble in all respects those seen in man. It is apparent that exposure levels were probably much higher than reported.
It is interesting to note that the estimated duration of exposure ranged from 6 weeks to 9-1/2 years for the cases listed in Table V. This would seem to indicate that for development of chronic beryllium disease, comparatively short time intervals are all that are necessary at the relatively low levels believed to be found in industry since 1949.
The Director of the Registry also indicates that the incidence of confirmed chronic beryllium disease is continuing and at least three new 98 cases will be admitted to the Beryllium Case Registry in 1972.
Information from the Beryllium Registry has been valuable in (1) criteria selection for diagnosis of beryllium poisoning, (2 ) judgment of effectiveness of controls, and (3) evaluation of the clinical course of beryllium disease and response to therapy. Hardy^^ points out, however, that there are three important deficiencies in the Registry:
(1) lack of knowledge of the size of population at risk; (2 ) incomplete data describing the amount of beryllium exposure; and (3) failure to learn of all cases of the disease in a beryllium-using industry.

# Neighborhood Cases
The term "neighborhood case" has been applied to a patient in which It has yet to be definitely established whether ambient air contamina tion alone, at a distance from a plant, can cause chronic beryllium disease.

# Correlation of Exposure and Effects

# Calculations
The percent of absorption is converted to absorbance. The standard curve is used to get a beryllium concentration value in terms of^ig/ml for the absorbance value. This jig Be/ml value is multiplied by the sample aliquot to determine the total beryllium in the sample.

# Calculation of Beryllium Concentration
Total jig Be m3 n f a i r aampiA " Jig Be/m of ambient air

# Effect of Storage
Samples and standards can be stored indefinitely without loss of beryllium as long as the pH of solutions is maintained at less than 2.
XI.

# APPENDIX III MATERIAL SAFETY DATA SHEET
The following items of information w hich are applicable to a specific product or material containing beryllium shall be provided In the appropriate section of the Material Safety Data Sheet or approved form. If a specific item of information is inapplicable (i.e., flash point) initials "n.a."
for not applicable shall be inserted.           Clean Sparkler Filter