Results of the Analysis of the Blood Beryllium Lymphocyte Proliferation Test Data from the Oak Ridge Y-12 Study

The potential hazards from exposure to beryllium or beryllium compounds in the workplace were first reported in the 1930s. The tritiated thymidine beryllium lymphocyte proliferation test (BeLPT) is an in vitro blood test that is widely used to screen beryllium exposed workers in the nuclear industry for sensitivity to beryllium. Newman [18] has discussed the clinical significance of the BeLPT and described a standard protocol that was developed in the late 1980s. Cell proliferation is measured by the incorporation of tritiated thymidine into dividing cells on two culture dates and using three concentrations of beryllium sulfate. Results are expressed as a “stimulation index” (SI) which is the ratio of the amount of tritiated thymidine (measured by beta counts) in the stimulated cells divided by the counts for the unstimulated cells on the same culture day. Several statistical methods for use in the routine analysis of the BeLPT were considered in the early 1990’s by Frome et al. [7]. The least absolute values (LAV) method was recommended for routine analysis of the BeLPT. The purposes of this report are to further evaluate the LAV method using new data, and to describe a new method for identification of an abnormal or borderline test. This new statisticalbiological positive (SBP) method reflects the clinical judgment that i) at least two SIs show a “positive” response to beryllium, and ii), that the maximum of the six SIs must exceed a cut point that is determined from a reference data set of normal individuals whose blood has been tested by the same method in the same serum. The new data is from the Y-12 facility in Oak Ridge and consist of 1080 worker and 33 nonexposed control BeLPTs (all tested in the same serum). Graphical results are presented to explain the statistical method, and the new SBP method is applied to the Y-12 group. The true positive rate and specificity of the new method were estimated to be 86 percent and 97 percent, respectively. The Department of Energy (DOE) has developed DOE-SPEC-1142-2001:BERYLLIUM LYMPHOCYTE PROLIFERATION TESTING [24] that describes the laboratory procedure and statistical analysis based on the SBP method for use in the BeLPT. DOE-SPEC-1142-2001 and the review process that was used to provide comments and improvements are available in an “electronic notebook”. The electronic notebook Notes Concerning the Tritiated Thymidine Beryllium Lymphocyte Proliferation Test (BeLPT-NB) can be accessed via the Internet at http://www.csm.ornl.gov/ û frome/BE/tnote.html.