Effect of tri- o-tolyl phosphate pretreatment on the toxicity and metabolism of parathion and paraoxon in mice

Abstract

Mice receiving po 400 mg/kg of tri- o-tolyl phosphate (TOTP) showed, 24 hr later, decreased mortality following parathion, Co-Ral, EPN, and DFP given po; increased mortality following TEPP, eserine and Guthion po; and no change in mortality following paraoxon po. TOTP administered ip also protected mice against parathion given po. TOTP pretreatment po increased mortality following ip and sc administration of parathion and paraoxon. Rate constants were obtained representing the change in brain cholinesterase activity with time following po or ip administration of parathion and paraoxon to control and TOTP-pretreated mice. The alteration of rate constants by TOTP pretreatment reflected the alteration of toxicity. Other effects of TOTP pretreatment included: (a) decrease in plasma but no change in liver A-esterase activity, (b) apparent decrease in tissue binding of paraoxon, (c) slight increase in the rate of conversion of parathion to paraoxon in liver microsomes and intestinal strips, and (d) decrease in hexobarbital but no change in barbital sleeping time. Liver microsomal nitrogen and liver weight were unaltered. It is suggested that TOTP pretreatment either increases the activity of liver detoxifying enzymes other than A-esterase or decreases the rate of absorption of parathion and paraoxon from the gut, or both.