An assessment of comparative acute toxicity of diisopropylfluorophosphate, tabun, sarin, and soman in relation to cholinergic and gabaergic enzyme activities in rats

Subbiah P. Sivam, Beth Hoskins, Ing K. Ho

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46 Scopus citations

Abstract

An Assessment of Comparative Acute Toxicity of Diisopropylfluorophosphate, Tabun, Sarin, and Soman in Relation to Cholinergic and GABAergic Enzyme Activities in Rats. SIVAM, S. P., HOSKJNS, B., AND HO, I. K. (1984). Fundam. Appl. Toxicol. 4, 531-538. The sc LD50s (μmol/kg) in rats for diisopropylfluorophosphate (DFP), Tabun, Sarin, and Soman were 14.5, 1.9, 1.4, and 0.88, respectively. The relative potency was as follows: DFP < Tabun < Sarin < Soman (1:7.6:10.4:16.4). The relative potencies correlated with the in Vitro acetylcholinesterase (AChE) inhibition (in terms of the IC50) by these compounds, in whole brain homogenates or the purified bovine erythrocyte AChE. There was a dose versus time for mortality relationship for all four compounds; the average time for death decreased with increase in dose. However, there was no correlation between time for death and the extent of AChE inhibition. The striatal as well as other regional (medulla, diencephalon, cortex, and cerebellum) AChE activity was inhibited over 90% of the control, by the lethal doses of these compounds. None of the lethal or sublethal doses had any apparent effect on choline acetyhransferase (CAT) or GABA-trans-aminase activities. Glutamic acid decarboxylase activity was increased by Soman, Sarin, and Tabun at certain lethal doses but was not affected by DFP even at the lethal dose. The results indicate that (a) the acute toxicity of organophosphate acetylcholinesterase inhibitors is directly related to the inhibition of AChE though there is a wide difference in their potency, (b) a substantial inhibition of AChE activity (over 90% of control) is necessary for lethality to ensue after an acute exposure and the margins between lethal and nonlethal doses are extremely small; and (c) qualitative differences seem to exist among the various organophosphates in affecting noncholinergic neurotransmitter enzymes.

Original languageEnglish (US)
Pages (from-to)531-538
Number of pages8
JournalToxicological Sciences
Volume4
Issue number4
DOIs
StatePublished - Aug 1 1984
Externally publishedYes

ASJC Scopus subject areas

  • Toxicology

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