Toxicological properties of trialkyl phosphorothioate and dialkyl alkyl- and arylphosphonothioate esters

J Environ Sci Health B. 1983;18(1):89-117. doi: 10.1080/03601238309372359.


Impurities such as O,S,S-trimethyl phosphorodithioate (TMPD) and the S-methyl isomer of malathion (isomalathion) strongly potentiated the mammalian toxicity of malathion. In contrast, impurities present in the phosphoramidothioate insecticide acephate had an antagonizing effect on its mammalian toxicity. The potentiation of the toxicity of malathion was attributed to inhibition of mammalian liver and serum carboxylesterase. O,O,S-Trimethyl phosphorothioate (TMP), another impurity present in technical malathion and in other organophosphorus insecticides, proved to be highly toxic. Rats given a single oral dose of TMP at a level as low as 20 mg/kg died over a period of three weeks, with death occurring with non-cholinergic signs of poisoning. TMPD also caused similar delayed death in rats. O,O,O-Trimethyl phosphorothioate (TMP=S), also another impurity in technical malathion and a structural isomer of TMP, was a potent antagonist to the delayed toxicity of TMP. Examination of a number of related trialkyl phosphorothioate and dialkyl alkylphosphonothioate esters revealed several of these compounds to be highly toxic to rats.

Publication types

  • Comparative Study
  • Research Support, U.S. Gov't, Non-P.H.S.
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Animals
  • Carboxylic Ester Hydrolases / antagonists & inhibitors
  • Drug Contamination*
  • Drug Synergism
  • Houseflies
  • Humans
  • Insecticides / toxicity
  • Kinetics
  • Malathion / pharmacology
  • Malathion / toxicity*
  • Mice
  • Organothiophosphates / toxicity*
  • Organothiophosphorus Compounds / antagonists & inhibitors
  • Organothiophosphorus Compounds / toxicity*
  • Phosphoramides
  • Rats


  • Insecticides
  • Organothiophosphates
  • Organothiophosphorus Compounds
  • Phosphoramides
  • O,O,O-trimethyl phosphorothioate
  • O,O,S-trimethyl phosphorothioate
  • O,S,S-trimethyl phosphorodithioate
  • acephate
  • isomalathion
  • Carboxylic Ester Hydrolases
  • malathion esterases
  • Malathion