Studies on the Biodisposition of Organophosphates in Mice

摘要

The biodisposition of diisopropylfluorophosphate (DFP), soman, and sarin was studied in the major organs of the mouse after i.v. administration of sublethal but pharmacologically active doses. DFP was also administered via inhalation, allowing comparison of disposition data between the two routes of administration. Only trace quantities of parent compounds were found in tissues. The major portion of the radioactivity was determined to be vocalently bound or free metabolites of the parent compounds. All compounds tested induced immediate hypothermia and hypoactivity lasting at least 7 hr. However, substantial quantities of radioactivity remained in the brain following recovery from the pharmacological effects. Cholinesterase inhibition was also not correlated with either free agent or bound or free metabolites, suggesting that non-cholinesterase binding of the parent compounds may play a role in the depression of CNS activity. The pharmacological effects of i.v. administered tabun were also evaluated and found to closely parallel those of DFP, sarin, and soman, although less potent. DF sarin and soman were distributed evenly throughout the mouse brain with slightly elevated levels in the hypothalamus. Concentrations of protein bound radioactivity were significantly elevated in the hypothalamus, and remained elevated for up to 24 hr. Thus, the hypothalamus may be an important site of the toxicity of organophosphates. Keywords: Tabun; psychological effects.