Toxicokinetic and toxicodynamic studies of beryllium.

The question of dose-effect relations of berylliosis was examined by measuring the Be-concentration in blood and urine, as well as the immunological behaviour of T-lymphocytes for a group of occupationally exposed men (smaller than 8 ng Be/m3, 4-6 h daily) and a non-exposed control group. Normal values 1.0 +/- 0.4 ng Be/g(n=10) in blood and 0.9 +/- 0.5 ng Be/g(n=10) in urine were found by an optimized flameless atomic absorption spectrometry method. The corresponding values for the exposed group (n=8) showed a mean increase of a factor of 4. The preferential enrichment of Be in the prealbumin and in the nu-globulin fractions was determined by a preparative isotachophoretic column with physiological pH conditions, especially developed for this application. The Be-specific stimulation of the T-lymphocytes of the exposed group was increased significantly. In blood and urine samples of exposed (2-40 mg Be/m3 as Be(NO3)2) Wistar-rats and guinea pigs Be values up to 36 ng Be/g in serum and up to 300 ng Be/g in urine were determined. After Be exposure, guinea pig serum showed a significant increase in the nu-globulins after the isotachophoretical separation of the serum proteins, which could not be correlated with increased Be-levels in this fraction. 70% of the total Be(10-100 ng/g serum) were detected in the prealbumin, only about 1% in the nu-globulin fraction. The same results were found in serum samples with in vitro addition of Be. The lymphocyte transformation rates for the exposed animals were increased. Skin tests were found to be positive in 70% for exposed rats and in 50-70% for guinea pigs.