The interaction between phosphorothionate insecticides, pneumotoxic trialkyl phosphorothiolates and effects on lung 7-ethoxycoumarin O-deethylase activity.
A number of phosphorothionate (P = S) insecticides, including bromophos and fenitrothion, prevent trialkyl phosphorothiolate (P = O)-induced lung toxicity and the resulting increase in lung weight normally observed at 3 days in the rat. Measurement of 7-ethoxycoumarin O-deethylase (7-EC) activity after both phosphorothionate and phosphorothiolate dosing revealed differing patterns of loss of enzyme activity. Depletion of 7-EC activity by phosphorothionates was maximal between 2 and 10 h after dosing, with recovery between 24 and 72 h. Phosphorothiolates, however, appear to cause two phases of loss of 7-EC activity, an initial fall of approximately 30% observed at 2 h and a secondary fall, maximal on day 3, with loss of 97% of activity, apparently associated with the pathological changes in the lung. It is suggested that oxidative metabolism of phosphorothionates known to occur at the P = S moiety, with suicidal loss of P-450, may then prevent oxidative activation of an S-methyl on the phosphorothiolates, the most likely site for production of a reactive intermediate capable of damaging the lung. Lung 7-EC in rat is sensitive to concentrations of the phosphorothionates bromophos and fenitrothion at 5-25 times less than those causing loss of liver 7-EC activity and at doses 125-600 times less than their LD50s. If repeated in man this may have implications for personnel occupationally exposed to these compounds.
D015660:7-Alkoxycoumarin O-Dealkylase; D000818:Animals; D005260:Female; D007306:Insecticides / Q000378:metabolism / Q000633:toxicity*; D008168:Lung / Q000187:drug effects / Q000201:enzymology* / Q000378:metabolism; D008861:Microsomes / Q000187:drug effects / Q000378:metabolism; D009929:Organ Size / Q000187:drug effects; D063086:Organothiophosphates / Q000633:toxicity*; D009946:Organothiophosphorus Compounds / Q000633:toxicity*; D010105:Oxygenases / Q000037:antagonists & inhibitors*; D051381:Rats; D011919:Rats, Inbred Strains; D013997:Time Factors
D007306:Insecticides; D063086:Organothiophosphates; D009946:Organothiophosphorus Compounds; D010105:Oxygenases; D015660:7-Alkoxycoumarin O-Dealkylase