EFFECTS OF ETHYL p-NITROPHENYL THIONOBENZENE PHOSPHONATE (EPN) ON THE TOXICITY OF ISOPROPYL METHYL PHOSPHONOFLUORIDATE (GB)

¹ Biochemical Research Division, U. S. Army Chemical Research and Development Laboratories, Army Chemical Center, Maryland

Pretreatment of female rats with 6 mg/kg of ethyl p-nitrophenyl thionobenzene phosphonate (EPN) intrapenitoneally resulted in marked potentiation of the toxicity of isopropyl methyl phosphonofluoridate (GB) when the latter compound was administered as a vapor or by intraperitoneal or intravenous injection.

Injection of GB labeled with P³² following EPN pretreatment resulted in 12-fold and 9-fold increases in protein-bound P³² from GB in brain and kidney tissue above that in rats not pretreated with EPN. This marked increase in binding of P³² in brain was consistent with the high inhibition of brain ChE activity, acute symptomatology and complete mortality obtained with low doses (asymptomatic in naive rats) of GB following EPN administration.

Marked reduction in the "sarinase" activity of liver and in the binding capacity of lung tissue for GB followed a single dose of EPN concurrent with enhanced susceptibility to the toxic action of GB. These findings are illustrative of possible modes of interference with detoxification mechanisms for GB which may serve to potentiate the toxicity of the latter compound.

This article has been cited by other articles:

				V. C. Moser, M. Casey, A. Hamm, W. H. Carter Jr., J. E. Simmons, and C. Gennings Neurotoxicological and Statistical Analyses of a Mixture of Five Organophosphorus Pesticides Using a Ray Design Toxicol. Sci., July 1, 2005; 86(1): 101 - 115. [Abstract] [Full Text] [PDF]