Beryllium carcinogenesis. II. Pulmonary deposition and clearance of inhaled beryllium sulfate in the rat.

Abstract

The pulmonary beryllium levels of rats exposed to the inhalation of BeSO4 aerosol at a concentration productive of lung cancer in 100% of the animals (34.25 µg of Be/cu m) showed a rate of accumulation which decreased during continuing exposure. After about 36 weeks, a tendency toward a concentration plateau was appearent in both sexes. The plateau is interpreted as equilibrium between deposition and clearance; mechanisms of the latter are shown to include not only the solubility of intrapulmonary precipitates formed in situ but also certain host-dependent factors involving primarily the lymphatic route. Females were distinctly less efficient than males in utilizing this route of clearance, resulting in slower removal of pulmonary Be deposits, markedly lower accumulation of the inhaled material in the regional lymph nodes, and earlier morbidity and mortality. Tracheobronchial lymph node loads reached peak values concurrently with the attainment of the pulmonary plateaus and showed a decrease from the 52nd week. This is interpretable as diminishing accumulation due to progressive impairment of the normal clearance routes during the exposure and as increasing rate of systemic dissemination from the lymph nodes with higher beryllium loads. Only about one-half of the original pulmonary load was cleared rapidly; the remainder tended to remain in the lungs for longer periods and probably became incorporated into the nuclei of certain pulmonary cells. This portion of the inhaled beryllium appears to be involved in the exertion of the carcinogenic challenge.