Acute inhalation toxicity of high concentrations of silane in male ICR mice

Abstract

In order to examine the toxicity of silane, male ICR mice were exposed to silane for 30 min (n=8), 1 or 4 h (n=12) at concentrations of 2500, 5000, 7500 (30-min experiment only) or 10000 ppm. In the 1- and 4-h experiments, 12 mice were divided into two sub-groups: four for 2-day observation and eight for 2-week observation. The mortality was six deaths out of eight mice exposed to 10000 ppm for 4 h. No deaths occurred in any of the other experiments. In the mice sacrificed 2 days after the exposure, acute renal tubular necrosis was observed at 10000 ppm (1-h exposure) or at 2500 ppm or more (4-h exposure). Reduction in body weight, increase in relative kidney weight and blood urea nitrogen (BUN) level, and splenic atrophy and inflammatory changes of the nasal mucosa were also seen in the 10000 ppm-4 h exposure group. In the mice sacrificed 2 weeks after the exposure, tubulo-interstitial nephritis (TIN) developed at 7500 ppm or more (30-min exposure) or at 5000 ppm or more (1- and 4-h exposure). BUN increased in a dose-dependent manner, and BUN in TIN positive mice was significantly higher than that in TIN negative mice (1- and 4-h exposure). No histopathological changes were observed in the glomeruli. These results indicate that the LC₅₀ of silane in mice is between 5000 and 10000 ppm for 4-h exposure and is greater than 10000 ppm for 1-h or 30-min exposure. The target site of silane toxicity is the renal tubule, and the no-observed-effect levels of silane for acute inhalation exposure in mice are 1000 ppm for 4-h exposure (from the previous report of our research group), 2500 ppm for 1-h exposure and 5000 ppm for 30-min exposure.