PT  - JOURNAL ARTICLE
AU  - Kenneth P. DuBois
AU  - John Doull
AU  - Paul R. Salerno
AU  - Julius M. Coon
TI  - STUDIES ON THE TOXICITY AND MECHANISM OF ACTION OF p-NITROPHENYL DIETHYL THIONOPHOSPHATE (PARATHION)
DP  - 1949 Jan 01
TA  - Journal of Pharmacology and Experimental Therapeutics
PG  - 79--91
VI  - 95
IP  - 1
4099  - http://jpet.aspetjournals.org/content/95/1/79.short
4100  - http://jpet.aspetjournals.org/content/95/1/79.full
SO  - J Pharmacol Exp Ther1949 Jan 01; 95
AB  - 1. Measurements of the acute toxicity of parathion given intraperitoneally gave the following approximate LD50 values in mgm./kgm.: male rats 7, female rats 4, mice 5-10, cats 3-5, and dogs 12-20. The LD50 by oral administration was 6 mgm./kgm. for female rats and 15 mgm./kgm. for male rats. 2. The LD50 for the oxygen analog of parathion, diethyl p-nitro phenylphosphate, was 1.2 mgm./kgm. when given intraperitoneally in rats and 3.5 mgm./kgm. when given orally with both sexes showing equal susceptibility. 3. Diethyl stilbesterol increased the susceptibility of male rats to parathion while testosterone propionate decreased the susceptibility of females to the insecticide. 4. A cumulative toxic action by parathion was observed in rats after daily administration of sublethal doses of the drug. 5. The symptoms produced by parathion were similar in all of the species tested and were typical of parasympathomimetic drugs. Pharmacodynamic studies showed irregular blood pressure responses to intravenous injection, a slight fall or rise, or a diphasic response being seen on different occasions. The depressor response to acetylcholine was augmented and atropine antagonized many of the effects of the drugs. After lethal doses of the drug death resulted from respiratory paralysis. 6. Parathion was found to be a strong inhibitor of cholinesterase. In vitro a final concentration of 1.2 x 10-6M parathion produced 50 per cent inhibition of rat brain cholinesterase. After 5 mgm./kgm. of the insecticide given intraperitoneally the cholinesterase activity of the brain was 15 per cent of normal while the submaxillary glands exhibited 29 per cent of control activity at the time of death. The free acetyicholine rose markedly in the brains of poisoned animals. 7. Treatment of rats with eserine before parathion resulted in partial protection of both the central and peripheral esterase against inhibition by the insecticide and a combination of atropine and eserine protected against the lethal action of the drug.