Toxicity studies of trimethylsilyldiazomethane administered by nose-only inhalation to Sprague Dawley (Hsd:Sprague Dawley SD) rats and B6C3F1/N mice.

Trimethylsilyldiazomethane (TMSD) is a methylating reagent widely used in organic chemistry. TMSD is structurally related to the compound diazomethane, which is a known lethal respiratory toxicant in humans and in animal models. TMSD is less reactive (with lower explosive potential) than diazomethane and is considered a safer, less toxic alternative. Few toxicity data are available to support this claim, however, and TMSD is readily available commercially from chemical suppliers. Concern over the inhalation toxicity of TMSD originates from reports of the death of two chemists resulting from lung injury and acute respiratory distress syndrome following exposure to TMSD in the workplace. Other concerns include the known inhalation toxicity of diazomethane and the absence of inhalation toxicity data for TMSD. The National Toxicology Program (NTP) conducted this study to evaluate the acute inhalation toxicity of TMSD in vivo.(Abstract Abridged).