Chlorosilane Acute Inhalation Toxicity and Development of an LC50 Prediction Model

The acute inhalation toxicity of 10 chlorosilanes was investigated in Fischer 344 rats using a 1-h whole-body vapor inhalation exposure and a 14-day recovery period. The median lethal concentration (LC50₁) for each material was calculated from the nominal exposure concentrations and mortality. Experimentally derived LC50₁ values for monochlorosilanes (4257–4478 ppm) were greater than those for dichlorosilanes (1785–2092 ppm), which were greater than those for trichlorosilanes (1257–1611 ppm). Apparent was a strong structure-activity relationship (r² = .97) between chlorine content and LC50₁ value. Estimated LC50₁ values for mono-, di-, and trichlorosilanes were determined to be 3262, 1639, and 1066 ppm, respectively, utilizing this relationship and the lower limit of the 95% prediction interval. The LC50₁ values determined in this series of studies were greater than that reported for hydrogen chloride (3124 ppm), when expressed on a chlorine equivalence basis (3570–5248 ppm), demonstrating that the acute toxicity of these chlorosilanes is similar to or less than that for hydrogen chloride. The good correlation between chlorine content and LC50₁ provides a sound basis for estimation of LC50₁ for chlorosilanes not already evaluated. The use of structure–activity relationships is consistent with the chemical industry and federal agency initiatives to reduce, refine, and/or replace the use of animals in testing without compromising the quality of health and safety assessments.