Related Experiment Videos
Oral and dermal absorption of chlorpyrifos: a human volunteer study
Objectives:
To determine the kinetics of elimination of urinary dialkylphosphate metabolites after oral and dermally applied doses of the organophosphate pesticide chlorpyrifos to human volunteers and to determine whether these doses affected plasma and erythrocyte cholinesterase activity.
Method:
Five volunteers ingested 1 mg (2852 nmol) of chlorpyrifos. Blood samples were taken over 24 hours and total void volumes of urine were collected over 100 hours. Four weeks later 28.59 mg (81567 nmol) of chlorpyrifos was administered dermally to each volunteer for 8 hours. Unabsorbed chlorpyrifos was washed from the skin and retained for subsequent measurement. The same blood and urine sampling regime was followed as for the oral administration. Plasma and erythrocyte cholinesterase concentrations were determined for each blood sample. The concentration of two urinary metabolites of chlorpyrifos--diethylphosphate and diethyl-thiophosphate--was determined for each urine sample.
Results:
The apparent elimination half life of urinary dialkylphosphates after 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 dermal dose was recovered as urinary metabolites. About half (53%) of the dermal dose was recovered from the skin surface. The absorption rate through the skin, as measured by urinary metabolites was 456 ng/cm2/h. Blood plasma and erythrocyte cholinesterase activity did not fall significantly during either dosing regime.
Conclusion:
An oral dose of chlorpyrifos was readily absorbed through the skin and almost all of the dose was recovered as urinary dialkylphosphate metabolites. Excretion was delayed compared with 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 samples for biological monitoring after dermal exposure is before the shift the next day. The amounts of chlorpyrifos used did not depress acetyl cholinesterase activity but could be readily detected as urinary dialkylphosphate metabolites indicating that the urinary assay is a more sensitive indicator of exposure.
Insights
Urinary dialkylphosphate metabolites indicate organophosphate pesticide chlorpyrifos exposure. Dermal absorption is significant, with delayed excretion compared to oral doses, making urinary assays sensitive biomonitoring tools.
Area of Science:
- Environmental Science
- Toxicology
- Human Health
Background:
- Organophosphate pesticides, like chlorpyrifos, pose risks through various exposure routes.
- Understanding chlorpyrifos metabolism and excretion is crucial for assessing human exposure and health risks.
Purpose of the Study:
- To investigate the elimination kinetics of urinary dialkylphosphate metabolites following oral and dermal exposure to chlorpyrifos in human volunteers.
- To assess the impact of these exposure routes on plasma and erythrocyte cholinesterase activity.
Main Methods:
- Human volunteers received oral (1 mg) and dermal (28.59 mg) doses of chlorpyrifos.
- Blood and urine samples were collected over 100 hours post-exposure.
- Urinary dialkylphosphate metabolites (diethylphosphate and diethyl-thiophosphate) and cholinesterase activity were quantified.
Main Results:
- The elimination half-life of urinary dialkylphosphates was 15.5 hours (oral) and 30 hours (dermal).
- Oral dose recovery as urinary metabolites was high (93%), while dermal recovery was low (1%), with 53% of the dermal dose remaining on the skin.
- Cholinesterase activity remained unaffected by either dosing regimen.
Conclusions:
- Chlorpyrifos is readily absorbed dermally, with excretion kinetics differing from oral intake.
- Urinary dialkylphosphate metabolite assays are sensitive indicators of chlorpyrifos exposure, even when cholinesterase activity is not significantly inhibited.
- Optimal urine sample collection for biological monitoring after dermal exposure is recommended prior to the next work shift.