Abstract
The acute toxicity of trimethyl and triethylphosphorothioates present as impurities in technical organophosphorus insecticides has been examined in rats. Although the majority of these compounds caused cholinergic signs, in some a second phase of toxicity affecting the lung was also seen. Rats after recovering from the cholinergic phase of poisoning showed respiratory distress and died 3–6 days after dosing with a massive increase in lung weight, associated with progressive diffuse interstitial thickening maximal on day 4. For two compounds no cholinergic toxicity was observed and narcosis was the predominant sign of poisoning.
Pretreatment with phenobarbitone, piperonyl butoxide or SKF525A protected rats against lung toxicity caused by trimethylphosphorothioate and dithioate but only phenobarbitone was effective against OOS-triethylphosphorothioate lung toxicity.
Direct intrabronchial instillation of OSS-trimethylphosphorodithioate and OOS-triethylphosphorothioate, both of which had been shown to cause lung damage after other routes of dosing, did not greatly increase the toxicity of these two compounds, suggesting that they are not directly toxic to the lung and probably require metabolism.
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References
Adamson IYR, Bowden DH, Cote MG, Witschi H (1977) Lung injury induced by butylated hydroxytoluene. Cytodynamic and biochemical studies in mice. Lab Invest 36: 26–32
Aldridge WN, Miles JW, Mount DL, Verschoyle RD (1979) The toxicological properties of impurities in malathion. Arch Toxicol 42: 95–106
Ali FAF, Fukuto TR (1982) Toxicity of OOS-trialkylphosphorothioates to the rat. J Agric Food Chem 30: 126–130
Bailey E, Peal JA, Verschoyle RD (1981) The Determination of O,S,S-trimethylphosphorodithioate in the plasma and various tissues of rats using high resolution gas chromatography with nitrogen phosphorus detection. J Chromatogr Sci 219:285–290
Clothier B, Johnson MK, Reiner E (1981) Interaction of some trialkylphosphorothiolates with acetylcholinesterase characterization or inhibition, aging and reactivation. Biochim Biophys Acta 660: 306–316
Deichman WMB, Witherup S (1946) Observations on the effects of trimethyl phosphate upon experimental animals. J Pharmacol Exp Ther 88: 338–342
Dinsdale D, Verschoyle RD, Cabral JRP (1982) Cellular responses to phosphorothioate-induced injury in rat lung. Arch Toxicol (in press)
Imamura T, Umetsu N, Fukuto TR (1982) The delayed toxic effect of O,O,S-trimethylphosphorothioate on in vivo protein synthesis studied in various rat organs. Abstracts of papers, 183 ACS National meeting, Las Vegas, Nevada, March 28–April 2, PEST 13
Kawano S, Nakao T, Hiraga K (1981) Strain differences in butylated hydroxytoluene induced deaths in male mice. Toxicol Appl Pharmacol 61:475–479
Mallipudi NM, Talcott RE, Ketterman A, Fukuto TR (1980) Properties and inhibition of rat malathion carboxylesterase. J Toxicol Environ Health 6: 585–596
Pellegrini G, Santi R (1972) Potentiation of toxicity of organophosphorus compounds containing carboxylic ester functions toward warm-blooded animals by some organophosphorus impurities. J Agric Food Chem 20: 944–950
Sanderson DM (1959) A note on glycerol formal as a solvent in toxicity testing. J Pharm Pharmacol 11: 150–156
Talcott RE, Mallipudi NM, Umetsu N, Fukuto TR (1979) Inactivation of esterases by impurities isolated from technical malathion. Toxicol Appl Pharmacol 49: 107–112
Toia RF, March RB, Umetsu N, Mallipudi NM, Allahyari R, Fukuto TR (1980) Identification and toxicological evaluation of impurities in technical malathion and fenthion. J Agric Food Chem 28: 599–604
Umetsu N, Grose FH, Allehyari R, Abu-El-Haj S, Fukuto TR (1977) Effect of impurities on the mammalian toxicity of technical malathion and acephate. J Agric Food Chem 25:946–953
Umetsu N, Toia RF, Mallipudi NM, March RB, Fukuto TR (1979) A novel antagonistic effect to the toxicity in the rat of O,O,S-trimethyl phosphorothioate by its phosphorothionate isomer. J Agric Food Chem 27:1423–1425
Umetsu N, Mallipudi NM, Toia RF, March RB, Fukuto TR (1981) Toxicological properties of phosphorothioate and related esters present as impurities in technical organophosphorus insecticides. J Toxicol Environ Health 7:481–497
Vandekar M (1957) Anaesthetic effect produced by organophosphorus compounds. Nature 179: 154–155
Verschoyle RD, Aldridge WN, Cabral JRP (1980) Toxicology of trimethyl and triethyl phosphorothioates. In: Holmstedt B, Lauwerys R, Mercier M, Roberfroid M (eds) Mechanisms of toxicity and hazard evaluation. Elsevier/North Holland Biomedical Press, Amsterdam, pp 631–634
Weil CS (1952) Tables for convenient calculation of median-effective dose (LD50 or ED50) and instructions in their use. Biometrics 8:249–263
Witschi H, Saheb W (1974) Stimulation of DNA synthesis in mouse lung following intraperitoneal injection of butylated hydroxytoluene. Proc Soc Exp Biol Med 147: 690–693
Wyatt I, Doss AW, Zavala DC, Smith LL (1981) Intrabronchial instillation of paraquat in rats:lung morphology and retention study. B J Ind Med 38: 42–48
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Verschoyle, R.D., Cabral, J.R.P. Investigation of the acute toxicity of some trimethyl and triethyl phosphorothioates with particular reference to those causing lung damage. Arch Toxicol 51, 221–231 (1982). https://doi.org/10.1007/BF00348854
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DOI: https://doi.org/10.1007/BF00348854