Oral and dermal absorption of chlorpyrifos: a human volunteer study

Objectives-To determine the kinetics of elimination of urinary dialkylphosp hate metabolites after oral and dermally applied doses of the organophospha te pesticide chlorpyrifos to human volunteers and to determine whether thes e doses affected plasma and erythrocyte cholinesterase activity. Method-Five volunteers ingested 1 mg (2852 nmol) of chlorpyrifos. Blood sam ples were taken over 24 hours and total void volumes of urine were collecte d over 100 hours. Four weeks later 28.59 mg (81567 nmol) of chlorpyrifos wa s administered dermally to each volunteer for 8 hours. Unabsorbed chlorpyri fos was washed from the skin and retained for subsequent measurement. The s ame blood and urine sampling regime was followed as for the oral administra tion. Plasma and erythrocyte cholinesterase concentrations were determined for each blood sample. The concentration of two urinary metabolites of chlo rpyrifos-diethylphosphate and diethylthiophosphate-was determined for each urine sample. Results-The apparent elimination half life of urinary dialkylphosphates aft er the oral dose was 15.5 hours and after the dermal dose it was 30 hours. Most of the oral dose (mean (range) 93% (55-115%)) and 1% of the applied de rmal dose was recovered as urinary metabolites. About half (53%) of the der mal dose was recovered from the skin surface. The absorption rate through t he skin, as measured by urinary metabolites was 456 ng/cm(2)/h. Blood plasm a and erythrocyte cholinesterase activity did not fall significantly during either dosing regime. Conclusion-An oral dose of chlorpyrifos was readily absorbed and almost all of the dose was recovered as urinary dialkylphosphate metabolites. Chlorpy rifos was also absorbed through the skin. Excretion was delayed compared wi th the oral dose. Only a small proportion of the applied dose was recovered during the course of the experiment. The best time to collect urine sample s for biological monitoring after dermal exposure is before the shift the n ext day. The amounts of chlorpyrifos used did not depress acetyl cholineste rase activity but could be readily detected as urinary dialkylphosphate met abolites indicating that the urinary assay is a more sensitive indicator of exposure.