Abstract
A rapid procedure for the measurement of brain, plasma and erythrocyte cholinesterase of rats is presented. Using this procedure, studies have been made on the toxicology and pharmacology of DFP, Parathion, TEPP, EPN, OMPA, and E-838. Data supporting the following conclusions are presented:
1. The oral LD50's for these compounds for male and female rats are DFP, 13.5 and 7.7 mgm./kgm.; Parathion 30 and 3 mgm./kgm.; TEPP 2 and 1.2 mgm./kgm.; EPN 91 and 14.5 mgm./kgm.; OMPA 13.5 and 35.5 mgm./kgm.; and E-838 42 and 19 mgm./kgm.
2. The administration of oral LD75 doses of these compounds caused brain cholinesterase inhibition varying with each compound: DFP > Parathion > E-838 > EPN > TEPP > OMPA.
3. The inhibition of brain cholinesterase does not appear to be directly responsible for death from these organic phosphorus compounds.
4. Oral LD75's of all compounds caused an inhibition of plasma and erythrocyte cholinesterase from 10 to 35 per cent of normal.
5. The degree of brain, plasma or erythrocyte cholinesterase inhibition does not directly parallel the symptomatology.
6. Following sublethal doses of these compounds, DFP alone causes irreversible brain cholinesterase inhibition.
7. All compounds cause irreversible erythrocyte cholinesterase inhibition.
8. Subacute feeding of all compounds leads to a cumulative inhibition of erythrocyte cholinesterase. The lowest level for each compound which exhibits this cumulative effect is: 25 ppm. EPN, 5 ppm. DFP, Parathion or E-838 and 1 ppm. OMPA.
9. All compounds exhibit essentially the same symptoms of poisoning and can be antidoted by atropine.
10. The mechanism of death appears possibly to be due primarily to peripheral inhibition of cholinesterase in the muscles, leading to respiratory paralysis, anoxia and terminal convulsion.
11. Discussion is made of the practical application of plasma and erythrocyte cholinesterase determinations to individuals acutely or chronically exposed to organic phosphates.
Footnotes
- Received February 4, 1952.
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