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

Details

• Personal Author:
  Lin Y ; Smith JN ; Timchalk C ; Wang J
• Description:
  Novel non-invasive techniques are being developed for biological monitoring (biomontitoring) of a variety of potential toxicants, including pesticides like chlorpyrifos (CPF); and saliva has been suggested as an ideal body fluid to biomonitor. In order to be acceptable, there is a need to understand salivary pharmacokinetics of CPF metabolites for extrapolation of saliva measurements to whole body exposures. In this context, in vivo pharmacokinetics of 3,5,6-trichloro-2-pyridinol (TCPy), a major 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 were very similar in blood and saliva (area under the curve (AUC) values were proportional and elimination rates ranged from 0.007 to 0.019 h-1) 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 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 accurately predicted TCPy concentrations in saliva over a range of blood concentrations. These studies suggest that saliva TCPy concentration can be utilized to ascertain CPF exposure, and 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:
  Agriculture Air Pollutants, Occupational Biochemistry Environmental Monitoring Hazardous Substances Hematologic Tests Hypersensitivity Laboratories Lung Occupational Health Particulate Matter Respiratory System Safety

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• Keywords:
  Agricultural-chemicals Airborne-particles Biohazards Biological-effects Biological-monitoring Blood-analysis Blood-sampling Chemical-hypersensitivity Exposure-assessment Exposure-levels Exposure-methods Inhalation-studies Laboratory-animals Laboratory-testing Particle-aerodynamics Particulates Physiological-chemistry Physiological-effects Physiological-measurements Physiological-response Physiological-testing Pulmonary-system Quantitative-analysis Salivary-glands Statistical-analysis Toxic-effects

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• ISSN:
  1096-6080
• Document Type:
  Text
• Funding:
  Grant
• Genre:
  Abstract or Summary
• Place as Subject:
  OSHA Region 10 ; OSHA Region 3 ; OSHA Region 8 ; Utah ; Washington ; West Virginia
• CIO:
  National Institute for Occupational Safety and Health (NIOSH)
• Topic:
  Workplace Safety & Health
• Location:
  North America
• Volume:
  114
• Issue:
  1
• NIOSHTIC Number:
  nn:20036669
• Citation:
  Toxicologist 2010 Mar; 114(1):397
• Federal Fiscal Year:
  2010
• NORA Priority Area:
  Agriculture, Forestry and Fishing ; Research Tools and Approaches: Exposure Assessment Methods
• Performing Organization:
  Battelle Pacific Northwest Laboratories
• Peer Reviewed:
  False
• Start Date:
  20060901
• Source Full Name:
  The Toxicologist. Society of Toxicology 49th Annual Meeting and ToxExpo, March 7-11, 2010, Salt Lake City, Utah
• End Date:
  20170831
• Collection(s):
  National Institute for Occupational Safety and Health
• Main Document Checksum:
  urn:sha-512:543a40e4cfe4ff6704e24c602eec854e35feaa0dd71116d67ca886f6f7328f4f6762948eb959b275a63bc9b8cae41048e1f8fbe3af703cf719322edb07c4abf3
• Download URL:
  https://stacks.cdc.gov/view/cdc/187999/cdc_187999_DS1.pdf
• File Type:
  [PDF - 726.34 KB ]