BOX S-1

Statement of Task for the Committee on Beryllium Alloy Exposures

In its first report, the committee will provide an independent review of the toxicologic, epidemiologic, and other relevant data on beryllium. It will review both carcinogenic and noncarcinogenic effects. In its second report, the committee will estimate chronic inhalation exposure levels for military personnel and civilian contractor workers that are unlikely to produce adverse health effects. The committee will provide carcinogenic risk estimates for various inhalation exposure levels. It will consider genetic susceptibility among worker subpopulations. If sufficient data are available, the committee will evaluate whether beryllium-alloy exposure levels should be different from those of other forms of beryllium because of differences in particle size. The committee will identify specific tests for worker surveillance and biomonitoring. It will also comment on the utility of the beryllium lymphocyte proliferation test (BeLPT). Specifically, the committee will determine the value of the borderline or a true positive test in predicting CBD, its utility in worker surveillance, further followup tests needed for workers with positive BeLPT results (such as thin-slice computed-tomography bronchoscopy and biopsy), the likelihood of developing CBD after a true positive test, and a standardized method for achieving consistent test results in different laboratories. The committee will consider whether there are more suitable tests that would be more accurate as screening or surveillance tools. The committee will also identify data gaps relevant to risk assessment of beryllium alloys and make recommendations for further research.

SENSITIZATION AND CHRONIC BERYLLIUM DISEASE

Clinical and Epidemiologic Studies

It is well established that beryllium can cause sensitization and CBD. Sensitization is an immune response, not a disease, and does not have any symptoms. It is usually detected with the beryllium lymphocyte proliferation test (BeLPT), an in vitro test that measures lymphocyte proliferation in peripheral blood cells or bronchoalveolar lavage (BAL) cells. CBD is a systemic granulomatous disorder that affects mainly the lungs. It can present with a variety of other effects that may include respiratory symptoms, radiographic abnormalities, and deficits in lung function. Since its pathogenesis involves a beryllium-specific, cell-mediated immune response, CBD cannot occur without sensitization.

Epidemiologic studies performed on cohorts of workers exposed to various forms of beryllium in different industries have indicated that sensitization and CBD can occur after exposure to beryllium even at concentrations below the current occupational exposure limit of 2 μg/m3. The studies have also shown that the incidence of CBD in workers depends on the industry or process, as well as the job category, and that sensitization does not always progress to CBD. There is growing evidence that skin exposure can contribute to sensitization and development of CBD.

Progression to CBD appears to be influenced not only by the magnitude of beryllium exposure but also by the physiochemical properties of the form of beryllium (such as composition and particle size), the genotype and phenotype of the exposed person, and probably the route of exposure. Other possible risk factors that have not been systematically addressed include smoking status, race, sex, concurrent exposures, and other environmental stressors. There is little published information on the rate of progression from asymptomatic immunologic sensitization to CBD.

Beryllium Lymphocyte Proliferation Test

In the BeLPT, a test for sensitization to beryllium, mononuclear cells derived from peripheral blood or BAL fluid are challenged with beryllium salts in vitro. A response is considered positive if beryllium induces proliferation of sensitized lymphocytes. The test is used both for diagnostic evaluation of CBD and for medical surveillance of workers. For example, a positive BeLPT result differentiates



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