Acute and subacute inhalation toxicity of germanium dioxide in rats

Two acute (4 hr) and one subacute (4 wk) inhalation toxicity studies on germanium dioxide ( purity ≥ 99%, mean particle size 1.7–2.6 μm) were conducted in young adult Wistar rats. In the acute studies, exposure of two groups of five rats of each sex to maximum attainable concentrations of either 3.10 g amorphous or 1.42 g hexagonal germanium dioxide/m 3 for 4 hr was not lethal. In the subacute study, four groups of five rats of each sex were exposed to 0, 16, 72 and 309 mg hexagonal germanium dioxide/m 3 for 6 hr/day, 5 days/wk during 4 wk. Two additional groups of 5 rats per sex, exposed either to 0 or to 309 mg/m 3, were kept for a 33-day post-exposure period. At the end of the treatment period, changes were observed only in rats of the high concentration group: these changes were decreased body weight gain (both sexes), decreases in haematocrit (females) and thrombocyte count (both sexes), and increases in neutrophil count (both sexes) and white blood cell count (females). On clinical chemistry evaluation, decreased fasting blood glucose (females), decreased total protein concentration (both sexes), increased plasma alanine aminotransferase and aspartate aminotransferase activities (females), increased plasma urea nitrogen (males) and increased plasma bilirubin level (females) were observed. In addition, urinary volume was elevated, and urine density and pH were lowered in both sexes. Relative weights of kidneys, spleen, heart and lungs were higher than in controls. Microscopic examination revealed effects on renal tubular epithelium. Effects on growth, kidneys, and liver were still present at the end of the 33-day recovery period. It was concluded that the 4-hr LC 50 value of amorphous germanium dioxide was greater than 3.10 g/m 3 and that of the hexagonal form greater than 1.42 g/m 3. The no-adverse-effect-level in the 4-wk study using hexagonal germanium dioxide was 72 mg/m 3.