title: Oral and dermal absorption of chlorpyrifos: a human volunteer study.
abstract: OBJECTIVE
  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.
  
  
  METHODS
  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.
  
  
  CONCLUSIONS
  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.
authors.affiliation: Health and Safety Laboratory, Sheffield, UK.
authors.forename: P
authors.initials: P
authors.lastname: Griffin
authors.forename: H
authors.initials: H
authors.lastname: Mason
authors.forename: K
authors.initials: K
authors.lastname: Heywood
authors.forename: J
authors.initials: J
authors.lastname: Cocker
mesh_terms: D000279:Administration, Cutaneous; D000284:Administration, Oral; D000328:Adult; D004390:Chlorpyrifos / Q000493:pharmacokinetics*; D002800:Cholinesterase Inhibitors / Q000493:pharmacokinetics*; D002802:Cholinesterases / Q000097:blood; D004781:Environmental Exposure; D004784:Environmental Monitoring / Q000379:methods*; D004912:Erythrocytes / Q000201:enzymology; D005260:Female; D006801:Humans; D007306:Insecticides / Q000493:pharmacokinetics*; D008297:Male; D008875:Middle Aged; D012869:Skin Absorption
chemical_list: D002800:Cholinesterase Inhibitors; D007306:Insecticides; D002802:Cholinesterases; D004390:Chlorpyrifos