Decreased Toxicity and Cholinesterase Inhibition in a New Series of Dithiophosphates1

Abstract

For parathion and a group of related phosphates there is, in general, a direct relationship between in vitro cholinesterase inhibition and in vivo toxicity. A new series of dithiophosphate esters has been discovered which have considerably less in vitro anti- cholinesterase activity in mice than in insects. An example of this series is malathon, S-(l,2-dicarbethoxyethyl) 0,0-dimethyl dithiophosphate, which is now a commercial product. Malathon and 3 analogues are compared with parathion with respect to toxicity on mice. Aphis rumicis Tribolium confusum Blattella germanica, and Oncopeltus fasciatus. Preliminary data show that although the acute oral LD50 of malathon (930 mg./kg.) on mice is about 1% that of parathion (9.7 mg./kg.), it is about 25-30% as toxic to many insects. The [image]. concn. of malathon for 50% cholinesterase inhibition (IN50) in mouse brain 1.5 x 10-4) and bee brain (1.5 x 10-5) compared with that of parathion is 2.5 x 10-6 and 1 x 10-6, respectively.