Biodisposition of Organophosphates in Guinea Pigs and Mice after Intramuscular, Intravenous and Inhalation Exposure

Abstract

The time course of 3H-soman and its metabolites was determined in tissues obtained from guinea pigs exposed to a sublethal dose of 3H-soman by either inhalation, intramuscular, or intravenous administration and mice exposed to a sublethal dose of 3H-soman by inhalation or intramuscular injection. Inhalation exposure of 3H-soman in mice resulted in rapid distribution from the lungs to all tissues, with concentrations remaining elevated as long as 24 hr after exposure. The intramuscular administration of 3H soman also resulted in a rapid distribution to all tissues, particularly the lungs and kidneys, with high concentrations still remaining in most tissues after 24 hr. Soman rapidly phosphorylated protein, and was quickly hydrolyzed to free 3H-PMPA. The biodisposition of 3H-soman and its metabolites was quite similar after both routes of administration, but contrasted with previous studies showing rapid clearance of organophosphates following intravenous administration. The biodisposition of 3H-soman and its metabolites in guinea pigs was highly dependent upon the route of administration. Following inhalation, the highest concentrations were found in lung, trachea, fat, and kidney 5 min after exposure. Concentrations of 3H-soman fell dramatically by the 30 min time point but then remained relatively constant for the duration of the time period studied. In contrast, intramuscular administration resulted in a sustained release of 3H-soman, with maximal concentrations achieved in most tissues (highest in lung, fat, heart, and kidney) at the 60 min time point and extremely elevated levels still remaining at 24 hr. Intravenous administration resulted in a rapid transfer to all tissues. RA 1, Soman, Organophosphates, Biodisposition, Inhalation.

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Document Details

Document Type
Technical Report
Publication Date
Jun 01, 1991
Accession Number
ADA247762

Entities

People

  • Billy R. Martin

Organizations

  • Virginia Commonwealth University School of Medicine

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DTIC Thesaurus Topics

  • Acetylcholinesterases
  • Air Flow
  • Alcohols
  • Animals
  • Blood
  • Classification
  • Intramuscular Injections
  • Laboratory Animals
  • Materials
  • Measurement
  • Metabolism
  • Plastic Explosives
  • Propylene Glycol
  • Rodents
  • Security
  • Standards
  • Toxicity

Fields of Study

  • Biology

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  • Immunology
  • Immunology and Pathology
  • Neurotoxicology