Aspects of vitamin A deficiency in the rat.

1. Marked differences in the duration of symptoms were observed when sublethal single doses of different dimethyl phosphate esters were injected intravenously into rats. The compounds inducing prolonged symptoms (OO-dimethyl S-ethylthioethyl phosphorothiolate, OO-dimethyl S-ethylsulphinylethyl phosphorothiolate and OO-dimethyl S-ethylsulphonylethyl phosphorothiolate) either persisted themselves, or produced an inhibitor which persisted for several hours in the blood. Those compounds inducing symptoms of short duration (OO-dimethyl S-ethylsulphonioethylmethyl phosphorothiolate and dimethyl p-nitrophenylphosphate) showed short persistence in the blood. 2. In vivo the rate of return of brain and erythrocyte cholinesterase activity differed markedly between the two groups of inhibitors. The persistent inhibitors produced irreversible inhibition of practically all of the inactivated enzyme, whereas most of the enzyme inhibited by the non-persistent inhibitors recovered its activity rapidly. 3. There was no distinction between the persistent and non-persistent inhibitors when tested in vitro for the return of cholinesterase activity by Aldridge's method. Return ofactivity took place at the same high rate in all instances, with a half-life of about 1-3 hr. 4. When the non-persistent inhibitor, Me-E 600, was made persistent by slow infusion for several hours into the rat's jugular vein, conversion into the second irreversible stage of inhibition took place. Decrease in the rate of infusion was followed by a remarkable increase in tolerance of inhibitor, with a parallel increase in production of irreversibly inhibited cholinesterase. 5. Because the conversion from the reversible into the irreversible stage occurs rapidly in vivo, it is concluded that both the persistence of the inhibitor and the route, or speed, or both, by which the dimethyl phosphate esters are administered will decide the extent to which this conversion will take place in the animal.