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 (LC50(1)) for each material was calculated from the nominal exposure concentrations and mortality. Experimentally derived LC50(1) 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 LC50(1) value. Estimated LC50(1) 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 LC50(1) 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 LC50(1) provides a sound basis for estimation of LC50(1) 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.
Jean
Paul A
PA
Dow Corning Corporation, Midland, Michigan 48686-0994, USA. paul.a.jean@dowcorning.com
Gallavan
Robert H
RH
Kolesar
Gary B
GB
Siddiqui
Waheed H
WH
Oxley
Jon A
JA
Meeks
Robert G
RG
D000280:Administration, Inhalation; D000818:Animals; D001835:Body Weight / Q000187:drug effects; D004305:Dose-Response Relationship, Drug; D007928:Lethal Dose 50; D008168:Lung / Q000187:drug effects; D015394:Molecular Structure; D051381:Rats; D011916:Rats, Inbred F344; D012119:Respiration / Q000187:drug effects; D012821:Silanes / Q000008:administration & dosage / Q000633:toxicity*; D013329:Structure-Activity Relationship; D014297:Trimethylsilyl Compounds / Q000008:administration & dosage / Q000633:toxicity*
D012821:Silanes; D014297:Trimethylsilyl Compounds; C099469:dichlorosilane; C039293:trimethylchlorosilane; C065893:trichlorosilane