[Effect of mixed function oxidases on phthalophos transformation in rat liver]. / Vliianie oksidaz smeshannoi funktsii na prevrashchenie ftalofosa v pecheni krys.

Phthalophos, organophosphoric pesticide, in the perfused isolated liver of rats transforms to water-soluble oxymethyl phthalimide and phthalimide. The induction of the liver hydroxylating enzymic system with milbex accelerates transformation of phthalophos: in 5 min only 14% of its initial amount is found in perfusate, while in the control--52%. The inhibition of the hydroxylating enzymic system with tetramethylthiuramdisulphide (dithiocarbamate pesticide) inhibits transformation of phthalophos: in 15 min perfusate contains 33% of its initial amount and the control--16%. Induction and inhibition of the hydroxylating enzymic system of the liver affect essentially the phthalophos toxicodynamics, decreasing the degree of the cholinesterase activity.

Metabolic and toxic behavior of phthalimide derivates. I. Fate of imidan in the fetus.

The organophosphate insecticide imidan includes a phthalimide group. Because of the structural relationship to the teratogenic compound thalidomide we have investigated its placental transfer and metabolic fate in rats. Its passage to embryonic tissues could be confirmed. After intraamniotic injection to the first amniotic cavity of the left uteri we could establish a distribution of imidan and 32P compounds throughout the uteri, the concentration depending upon the incubation time and the distances from the place of injection. The half-life of imidan, detected in the exterioized fetuses or in newborns, was 50--70 min. Imidoxon, i.e., the oxidized form of imidan, has a diminished half-life. This fact explicates the presence of imidoxon only in small concentrations after application of imidan.

Experimental study of the effect of a series of phosphoroorganic pesticides (Dipterex and Imidan) on embryogenesis.

Experiments conducted on pregnant Wistar rats show that chlorophos (Dipterex) has embroyotoxic and teratogenic effects after oral introduction in a 80 mg/kg dose during a critical period of embryogenesis. Embryotoxic and teratogenic effects are absent during the introduction of 8 mg/kg of the pesticide. The oral introduction of phthalophos (Imidan) in a 30 mg/kg dose once on day 9 of pregnancy and the introduction of a 1.5 mg/kg dose daily throughout the course of pregnancy caused increased postimplantation mortality of embryos. A dose of 30 mg/kg of phthalophos on day 9 or day 13 of pregnancy causes developmental abnormalities, including hyponathia and hydrocephaly. A 0.06 mg/kg phthalophos dose does not affect the course of embryogenesis in white rats. Thus the organophosphate pesticides Dipterex and Imidan exhibit embryotoxic and teratogenic effects at doses which significantly exceed the acutal amounts of the pesticide that can enter the human organism.