Abstract

Blood and brain concentrations and the in vitro metabolism of triethyl phosphate (TEP) in rats were studied in an attempt to determine the basis for the age differences in duration of narcosis produced by this compound. The duration of TEP-induced narcosis was determined in male and female rats between 5 and 90 days of age by measuring the duration of loss of righting reflex. TEP concentrations in chloroform extracts of blood and brain or of incubates of TEP with liver slices were measured by colorimetric determination of inorganic phosphorus after digestion or by gas chromatography. The duration of TEP narcosis in 2- to 6-week-old male and female rats was only about one-third the duration in 5-day-old or adult rats. The brain concentrations of TEP at the time of recovery from narcosis after 500 mg/kg of TEP were the same in both adult and weanling rats. The disappearance of TEP from the brain appeared to occur in two phases with the second phase being more rapid in weanlings than adults. In vitro metabolism of TEP by liver slices from weanlings was greater than by liver slices from adults. Phenobarbital and SKF 525A pretreatment, respectively, stimulated and inhibited disappearance of TEP both in vivo and in vitro. It appeared that a higher rate of metabolism by weanling rats resulted in lower initial concentrations of TEP in the brain and, therefore, the time required for redistribution out of the brain was less, resulting in shorter durations of narcosis.