Effects of subchronic parathion administration on sodium salicylate excretion kinetics in female rats

Organophosphorus (OP) pesticides are considered to be environmental contaminants, and chronic exposure to low levels through the diet may affect drug action. To study this possible interaction, ethyl parathion was administered by intubation to female rats for 35 consecutive days at a dose of 0.05 or 0.2 mg/kg of body weight per day. At 7, 21 and 35 days after parathion was initiated, rats were administered a single dose of 20 mg/kg sodium salicylate intraperitoneally. Total salicylates, salicylic acid (SA), salicyluric acid (SU) and gentisic acid (GA) were determined in urine. At 7 days, parathion treatment slowed the excretion of total salicylates. This effect was more evident at longer treatment times. Total excretion of SA was increased at the expense of GA at 7 days. However, this effect was reversed at 21 and 35 days. Excretion of SU was drastically diminished after 21 days of treatment with parathion. The results suggest that subchronic oral administration of parathion to female rats changes the excretion kinetics of sodium salicylate through combined effects on renal excretion mechanisms and biotransformation processes. Thus, exposure to low concentrations of environmental contaminants may produce important changes in drug action.