Chlorosilane Acute Inhalation Toxicity and Development of an LC50 Prediction Model

• Published in: Inhalation toxicology 2006-07, Vol.18 (8), p.515-522
• Main Authors: Jean, Paul A., Gallavan, Robert H., Kolesar, Gary B., Siddiqui, Waheed H., Oxley, Jon A., Meeks, Robert G.
• Format: Article
• Language: English
• Subjects: Administration, Inhalation; Animals; Body Weight - drug effects; Dose-Response Relationship, Drug; Lethal Dose 50; Lung - drug effects; Molecular Structure; Rats; Rats, Inbred F344; Respiration - drug effects; Silanes - administration & dosage; Silanes - toxicity; Structure-Activity Relationship; Trimethylsilyl Compounds - administration & dosage; Trimethylsilyl Compounds - toxicity
• ISSN: 0895-8378; 1091-7691
• DOI: 10.1080/08958370600686093

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.