Measurement of beryllium in biological samples by accelerator mass spectrometry: Applications for studying chronic beryllium disease

A method using accelerator mass spectrometry (AMS) has been developed for quantifying attomoles of beryllium (Be) in biological samples. This method provides the sensitivity to trace Be in biological samples at very low doses with the purpose of identifying the molecular targets involved in chronic beryllium disease. Proof of the method was tested by administering 0.001, 0.05, 0.5, and 5.0 μg of ⁹Be and ¹⁰Be by intraperitoneal injection to male mice and removing the spleen, liver, femurs, blood, lungs, and kidneys after 24 h of exposure. These samples were prepared for AMS analysis by tissue digestion in nitric acid, followed by further organic oxidation with hydrogen peroxide and ammonium persulfate and, last, precipitation of Be with ammonium hydroxide and conversion to beryllium oxide at 800 °C. The ¹⁰Be/⁹Be ratio of the extracted beryllium oxide was measured by AMS, and Be in the original sample was calculated. Results indicate that Be levels were dose-dependent in all tissues and the highest levels were measured in the spleen and liver. The measured ¹⁰Be/⁹Be ratios spanned 4 orders of magnitude, from 10^-10 to 10^-14, with a detection limit of 3.0 × 10^-14, which is equivalent to 0.8 amol of ¹⁰Be. These results show that routine quantification of nanogram levels of Be in tissues is possible and that AMS is a sensitive method that can be used in biological studies to understand the molecular dosimetry of Be and mechanisms of toxicity.