Pharmacokinetics of the Chlorpyrifos Metabolite 3,5, 6-Trichloro-2-Pyridinol (TCPy) in Rat Saliva

Details

• Personal Author:
  Lin Y ; Smith JN ; Timchalk C ; Wang J
• Description:
  Biological monitoring (biomonitoring) to quantify systemic exposure to the organophosphorus insecticide chlorpyrifos (CPF) has historically focused on the quantitation of major CPF metabolites in urine. Noninvasive techniques are being advocated as novel means of biomonitoring for a variety of potential toxicants, including pesticides (like CPF), and saliva has been suggested as an ideal body fluid. However, in order to be acceptable, there is a need to understand salivary pharmacokinetics of CPF metabolites in order to extrapolate saliva measurements to whole-body exposures. In this context, in vivo pharmacokinetics of 3,5,6-trichloro-2-pyridinol (TCPy), the major chemical-specific metabolite of CPF, was quantitatively evaluated in rat saliva. Experimental results suggest that TCPy partitioning from plasma to saliva in rats is relatively constant over a range of varying physiological conditions. TCPy pharmacokinetics was very similar in blood and saliva (area under the curve values were proportional and elimination rates ranged from 0.007 to 0.019 per hour), and saliva/blood TCPy concentration ratios were not affected by TCPy concentration in blood (p = 0.35) or saliva flow rate (p = 0.26). The TCPy concentration in saliva was highly correlated to the amount of unbound TCPy in plasma (r = 0.96), and the amount of TCPy protein binding in plasma was substantial (98.5%). The median saliva/blood concentration ratio (0.049) was integrated as a saliva/blood TCPy partitioning coefficient within an existing physiologically based pharmacokinetic and pharmacodynamic (PBPK/PD) model for CPF. The model was capable of accurately predicting TCPy concentrations in saliva over a range of blood concentrations. These studies suggest that saliva TCPy concentration can be utilized to ascertain CPF exposure. It is envisioned that the PBPK/PD can likewise be used to estimate CPF dosimetry based on the quantitation of TCPy in spot saliva samples obtained from biomonitoring studies. [Description provided by NIOSH]
• Subjects:
  Biochemistry Energy Metabolism Environmental Monitoring Hazardous Substances Insecticides Laboratories Occupational Health Organophosphates Risk Assessment Risk Factors Safety

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• Keywords:
  3,5,6-trichloro-2-pyridinol Author Keywords: Chlorpyrifos Biochemical-tests Biodynamics Biological-effects Biological-monitoring Biological-transport Biomonitoring Biostatistics Exposure-assessment Exposure-levels Exposure-methods Laboratory-animals Laboratory-testing Metabolic-study Organo-phosphorus-compounds Pesticides Pesticides-and-agricultural-chemicals Pharmacodynamics Pharmacokinetics Quantitative-analysis Risk-analysis Risk-factors Saliva Toxic-effects Toxins Trichloropyridinol

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• ISSN:
  1096-6080
• 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:
  315-325
• Volume:
  113
• Issue:
  2
• NIOSHTIC Number:
  nn:20036505
• Citation:
  Toxicol Sci 2010 Feb; 113(2):315-325
• Contact Point Address:
  Charles Timchalk, Battelle Memorial Institute, Pacific Northwest Division, PO Box 999, Richland, WA 99354
• Email:
  charles.timchalk@pnl.gov
• 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:
  Toxicological Sciences
• End Date:
  20050929
• Collection(s):
  National Institute for Occupational Safety and Health
• Main Document Checksum:
  urn:sha-512:3664af1438c1731d497461942533787e9e04ce0910eb6dcb977a3c83de9572e9206996fe2cfa4d08f09ae8cf8fab1d15eec0d4f11792fd36973f7ffb17a49ecc
• Download URL:
  https://stacks.cdc.gov/view/cdc/187900/cdc_187900_DS1.pdf
• File Type:
  [PDF - 454.11 KB ]