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The toxicological properties of impurities in malathion

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Abstract

During a malaria eradication programme in Pakistan in 1976, out of 7,500 spraymen, 2,800 became poisoned and 5 died. The major determinant of this poisoning has been identified as isomalathion present as an impurity in the malathion. It seems almost certain that the isomalathion was produced during storage of the formulated malathion.

The quantitative correlation found between isomalathion content and toxicity of many field samples of malathion has been confirmed by an examination of mixtures of pure compounds. Addition of known amounts of isomalathion to technical malathion indicates that other active substances are present. These impurities have been identified (trimethyl phosphorothioates) and have been shown to behave like isomalathion in potentiating the toxicity of malathion. Some preliminary work on their toxicological properties is reported.

The mechanisms involved in the potentiation of the toxicity of malathion are discussed.

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References

  • Aaron, H. S., Michal, H. O., Witton, B., Millar, J. J.: The stereochemistry of asymmetric phosphorus compounds. II. Stereospecificity of the irreversible inactivation of cholinesterase by the enantio-morphs of an organophosphorus inhibitor. J. Am. Chem. Soc. 80, 456–458 (1958)

    Google Scholar 

  • Baker, E.L., Zack, M., Miles, J. W., Alderman, L., Warren, McW., Dobbin, R. D., Miller, S., Teeters, W. R.: Epidemic malathion poisoning in pakistan malaria workers. Lancet I 1978, 31–33

  • Benschop, H. P.: The absolute configuration of chiral organophosphorus anticholinesterases. Pest. Biochem. & Physiol. 5, 348–349 (1975)

    Google Scholar 

  • Bhagwat, V. M., Ramachandran, B. V.: Malathion A and B-esterases of mouse liver. I. Separation and properties. Biochem. Pharmacol. 24, 1713–1717 (1975a)

    Google Scholar 

  • Bhagwat, V. M., Ramachandran, B. V.: Malathion A and B-esterases of mouse liver. II. Effect of EPN in vitro and in vivo. Biochem. Pharmacol. 24, 1727–1729 (1975b)

    Google Scholar 

  • Boter, H. L., Van Dijk, C.: Inhibition of acetylcholinesterase and butyrylcholinesterase by enantiomeric forms of sarin. Biochem. Pharmacol. 18, 2403–2407 (1969)

    Google Scholar 

  • Boter, H. L., Ooms, A. J. J.: Stereospecificity of hydrolytic enzymes in their reaction with optically active organophosphorus compounds. II. The inhibition of aliesterases, acetylesterases, chymotrypsin and trypsin by S-alkyl p-nitrophenyl methylphosphonothiolates. Biochem. Pharmacol. 16, 1563–1569 (1967)

    Google Scholar 

  • Casida, J. E.: Specificity of substituted phenylphosphorus compounds for esterase inhibition in mice. Biochem. Pharmacol. 5, 332–342 (1961)

    Google Scholar 

  • Casida, J. E., Baron, R. L., Eto, M., Engel, J. L.: Potentiation and Neurotoxicity induced by certain organophosphates. Biochem. Pharmacol. 12, 73–83 (1963)

    Google Scholar 

  • Chen, P. R., Tucker, W. P., Dauterman, W. C.: Structure of biologically produced malathion monoacid. J. Agric Food Chem. 17, 86–90 (1969)

    Google Scholar 

  • Cohen, S. D., Murphy, S. D.: Comparative potentiation of malathion by triorthotolyl phosphate in four classes of vertebrates. Toxicol. Appl. Pharmacol. 16, 701–708 (1970)

    Google Scholar 

  • Cohen, S. D., Murphy, S. D.: Carboxylesterase inhibition as an indicator of malathion potentiation in mice. J. Pharmacol. 176, 738–42 (1971a)

    Google Scholar 

  • Cohen, S. D., Murphy, S. D.: Malathion potentiation and inhibition of hydrolysis of various carboxylic esters by triorthotolylphosphate (TOTP) in mice. Biochem. Pharmacol. 20, 575–587 (1971b)

    Google Scholar 

  • Cook, J. W., Blake, J. R., Yip, G., Williams, M.: Malathionase. I. Activity and inhibition. J. Ass. Offic. Agri. Chem. 41, 399–407 (1958)

    Google Scholar 

  • Dauterman, W. C., Main, A. R.: Relationship between acute toxicity and in vitro inhibition and hydrolysis of a series of carbalkoxy homologues of malathion. Toxicol. Appl. Pharmacol. 9, 408–418 (1966)

    Google Scholar 

  • De Jong, L. P. A., Van Dijk, C.: Inhibition of acetylcholinesterases by the enantiomers of isopropyl S-2-trimethylammoniumethyl methylphosphonothioate iodide. Affinity and phosphorylation constants. Biochim. Biophys. Acta. 268, 680–689 (1972)

    Google Scholar 

  • Frawley, J. P., Fuyat, H. N., Hagan, E. C., Blake, J. R., Fitzhugh, O. G.: Marked potentiation in mammalian toxicity from simultaneous administration of two anticholinesterase compounds. J. Pharmacol. 121, 96–106 (1957)

    Google Scholar 

  • Hassan, A., Dauterman, W. C.: Studies on the optically active isomers of O,O-diethyl malathion and O,O-diethylmalaoxon. Biochem. Pharmacol. 17, 1431–1439 (1968)

    Google Scholar 

  • Hilgetag, G., Lehmann, G.: Thiophosphates. VII. Optical active thiophosphates. J. prakt. Chem. 8, 224–234 (1959)

    Google Scholar 

  • Keijer, J. H., Wolring, G. Z.: Stereospecific ageing of phosphorylated cholinesterases. Biochim. Biophys. Acta. 185, 465–468 (1969)

    Google Scholar 

  • Main, A. R., Braid, D. E.: Hydrolysis of malathion by ali-esterases in vitro and in vivo. Biochem. J. 84, 255–263 (1962)

    Google Scholar 

  • Main, A. R., Dauterman, W. C.: Kinetics for the inhibition of carboxylesterase by malaoxon. Can. J. Biochem. 45, 757–771 (1967)

    Google Scholar 

  • Miles, J. W., Mount, D. L., Staiger, M. A., Teeters, W. R.: S-methyl isomer content of stored malathion and fenitrothion powders and its relationship to toxicity. Presented at the Fourth International Congress of Pesticide Chemistry (IUPAC) Zurich, Switzerland, July 24–28, 1978

  • Murphy, S. D.: Malathion inhibition of esterases as a determinant of malathion toxicity. J. Pharmacol. 156, 352–365 (1967)

    Google Scholar 

  • Murphy, S. D., DuBois, K. P.: Quantitative measurement of inhibition of the enzymatic detoxification of malathion by EPN (ethyl p-nitrophenyl thionobenzenephosphonate). Proc. Soc. Exp. Biol. Med. 96, 813–818 (1957)

    Google Scholar 

  • Ooms, A. J. J., Boter, H. L.: Stereospecificity of hydrolytic enzymes in their reaction with optically active organophosphorus compounds. I. The reaction of cholinesterase and paraoxonase with S-alkyl p-nitrophenyl methylphosphonothiolates. Biochem. Pharmacol. 14, 1839–1846 (1965)

    Google Scholar 

  • Ooms, A. J. J., Van Dijk, C.: Reaction of organophosphorus compounds with hydrolytic enzymes. III. Inhibition of chymotrypsin and kypsin. Biochem. Pharmacol. 15, 1361–1377 (1966)

    Google Scholar 

  • Pellegrini, G., Santi, R.: Potentiation of toxicity of organophosphorus compounds containing carboxyl-ic ester functions toward warm-blooded animals by some organophosphorus impurities. J. Agric. Food. Chem. 20, 944–950 (1972)

    Google Scholar 

  • Sanderson, D. M.: A note on glycerol formal as a solvent in toxicity testing. J. Pharmacol. 11, 150–156 (1959)

    Google Scholar 

  • Schoene, K.: “Titration” of acetylcholinesterase with soman. Biochem. Pharmacol. 20, 2527–2528 (1971)

    Google Scholar 

  • Umetsu, N., Grose, F. H., Allahyari, R., Abu-El-Haj, S., Fukuto, T. R.: Effect of impurities on the mammalian toxicity of technical malathion and acephate. J. Agric. Food Chem. 25, 946–953 (1977)

    Google Scholar 

  • Vandekar, M.: Anaesthetic effect produced by organophosphorus compounds. Nature 179, 154–155 (1957)

    Google Scholar 

  • Wayne, R. S.: Collaborative Study of the Determination of Malathion in Formulations and Technical Materials by Gas-Liquid Chromatography JAOAC (In Press, 1978)

  • Weil, C.S.: Tables for convenient calculation of median-effective dose (LD50 or ED50) and instructions in their use. Biometrics 8, 249–263 (1952)

    Google Scholar 

  • Wustner, D. A., Fukuto, T. R.: Affinity and phosphorylation constants for the inhibition of cholinesterases by the optical isomers of O-2-butyl S-2 (dimethylammonium) ethyl ethylphosphonothioate hydrogen oxalate. Pestic. Biochem. Physiol. 4, 365–376 (1974)

    Google Scholar 

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Aldridge, W.N., Miles, J.W., Mount, D.L. et al. The toxicological properties of impurities in malathion. Arch Toxicol 42, 95–106 (1978). https://doi.org/10.1007/BF00316489

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