Comparative Pharmacokinetics of Chlorpyrifos Versus Its Major Metabolites Following Oral Administration in the Rat

Details

• Personal Author:
  Barr DB ; Busby-Hjerpe AL ; Campbell JA ; Lee, Stephen A. ; Poet TS ; Smith JN ; Timchalk C
• Description:
  Chlorpyrifos (CPF) is a commonly used diethylphosphorothionate organophosphorus (OP) insecticide. Diethylphosphate (DEP), diethylthiophosphate (DETP) and 3,5,6-trichloro-2-pyridinol (TCPy) are products of both in vivo metabolism and environmental degradation of CPF and are routinely measured in urine as biomarkers of exposure. Hence, urinary biomonitoring of TCPy, DEP and DETP may be reflective of an individual's contact with both the parent pesticide and exposure to these metabolites in the environment. In the current study, simultaneous dosing of 13C- or 2H-isotopically labeled CPF (13C-labeled CPF, 5 13C on the TCPy ring; or 2H-labeled CPF, diethyl-D10 (deuterium labeled) on the side chain) were exploited to directly compare the pharmacokinetics and metabolism of CPF with TCPy, and DETP. The key objective in the current study was to quantitatively evaluate the pharmacokinetics of the individual metabolites relative to their formation following a dose of CPF. Individual metabolites were co-administered (oral gavage) with the parent compound at equal molar doses (14 micromol/kg; approximately 5 mg/kg CPF). Major differences in the pharmacokinetics between CPF and metabolite doses were observed within the first 3h of exposure, due to the required metabolism of CPF to initially form TCPy and DETP. Nonetheless, once a substantial amount of CPF has been metabolized (> or =3h post-dosing) pharmacokinetics for both treatment groups and metabolites were very comparable. Urinary excretion rates for orally administered TCPy and DETP relative to 13C-CPF or (2)H-CPF derived 13C-TCPy and 2H-DETP were consistent with blood pharmacokinetics, and the urinary clearance of metabolite dosed groups were comparable with the results for the 13C- and 2H-CPF groups. Since the pharmacokinetics of the individual metabolites were not modified by co-exposure to CPF; it suggests that environmental exposure to low dose mixtures of pesticides and metabolites will not impact their pharmacokinetics. [Description provided by NIOSH]
• Subjects:
  Biological Factors Biomarkers Chemistry Environmental Exposure Environmental Monitoring Hypersensitivity Insecticides Laboratories Occupational Health Safety
• Keywords:
  Author Keywords: Chlorpyrifos Biological-effects Biological-factors Biological-systems Chemical-hypersensitivity Chemical-reactions Diethylthiophosphate Environmental-exposure Exposure-assessment Exposure-levels Exposure-limits Exposure-methods In-vivo-studies Laboratory-animals Pesticides Pharmacodynamics Pharmacokinetics Quantitative-analysis Trichloropyridinol

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• ISSN:
  0300-483X
• Document Type:
  Text
• Funding:
  Grant
• Genre:
  Journal Article
• Place as Subject:
  OSHA Region 10 ; Washington
• CIO:
  National Institute for Occupational Safety and Health (NIOSH)
• Topic:
  Workplace Safety & Health
• Location:
  North America
• Pages in Document:
  55-63
• Volume:
  268
• Issue:
  1
• NIOSHTIC Number:
  nn:20036473
• Citation:
  Toxicology 2010 Jan; 268(1-2):55-63
• Contact Point Address:
  Charles Timchalk, Battelle, Pacific Northwest Division, P.O. Box 999, Richland, WA 99354
• CAS Registry Number:
  Chlorpyrifos (CAS RN 2921-88-2)
• Federal Fiscal Year:
  2010
• NORA Priority Area:
  Research Tools and Approaches: Exposure Assessment Methods ; Agriculture, Forestry and Fishing
• Performing Organization:
  Battelle Memorial Institute, Richland, Washington
• Peer Reviewed:
  True
• Start Date:
  20010930
• Source Full Name:
  Toxicology
• End Date:
  20050929
• Collection(s):
  National Institute for Occupational Safety and Health
• Main Document Checksum:
  urn:sha-512:eae63eaea2778b5f9c8d2d9eb414f3a353bc129a882d99e3939595b7a1584bbe587ae76fa9964d90dac1eb31ed41c6f83413906e64845d8ae714cbd82aac30cb
• Download URL:
  https://stacks.cdc.gov/view/cdc/187882/cdc_187882_DS1.pdf
• File Type:
  [PDF - 644.41 KB ]