Effect of carbon tetrachloride on activation and detoxification of organophosphorus insecticides in the rat.

Carbon tetrachloride, 250 or 500 μl/kg, was administered po to rats 24 hr before the insecticide administration. After pretreatment with CCl₄ no signs of fenitrothion poisoning (75% LD50) were observed, but signs of chlorfenvinphos, disulfoton, or dichlorvos poisoning were similar to those observed in the control groups. The liver concentrations of fenitrothion and chlorfenvinphos were increased after pretreatment with CCl₄. The degradation of fenitrothion, chlorfenvinphos, and disulfoton by liver homogenates was diminished after CCl₄ pretreatment. Fenitrothion, parathion, disulfoton, ronnel, bromophos, chlorfenvinphos and bromfenvinphos cause type I substrate-cytochrome P-450 binding spectra. Difference spectra with dichlorvos, trichlorfon, or polfos were not detectable. These results suggest that most of the organophosphorus insecticides may be metabolized by mixed function oxidase systems and cytochrome P-450. The susceptibility of rats to poisoning by fenitrothion or derivative dialkyl aryl thiophosphates depends upon the activity of the mixed function oxidase system.