PBPK/PD Modeling of Chlorpyrifos in Sensitive Populations: Implications for Biomonitoring of Exposure

Details

• Personal Author:
  Busby AL ; Campbell JA ; Poet TS ; Timchalk C
• Description:
  Trichloropyridinol (TCPy) is the major metabolite of chlorpyrifos (CPF) and is used as a biomarker for exposure. TCPy has also been detected as residues on food and in the environment. Therefore, to quantitatively utilize TCPy as a CPF biomarker requires a more detailed understanding of TCPy pharmacokinetics. Laboratory research has elucidated the different pharmacokinetic behavior of TCPy from a CPF dose or from direct exposure to TCPy, and physiologically based pharmacokinetic/pharmacodynamic (PBPK/PD) modeling was implemented to quantify and interpret exposures. The model was interrogated to estimate the effects of metabolic variability associated with pregnant women and children and equate those effects against urinary TCPy concentrations. The worst-case scenario modeled a child with a 90% deficit in PON1 activity (the fifth percentile in newborns). At a 3 ug/kg dose, the maximal plasma cholinesterase (ChE) inhibition in these individuals was less than 4% (96.2% of control). In all adult simulations, differences in maximal plasma ChE inhibition were nominal at exposures up to 10 mg/kg. Regardless of exposure scenario, the urinary elimination of TCPy over the first 24 hr was unchanged, indicating that biomonitoring of urinary TCPy cannot be used to predict PON1, ChE, or P450 activities in individuals. [Description provided by NIOSH]
• Subjects:
  Behavior Biomarkers Energy Metabolism Environmental Exposure Occupational Health Safety Urine Women
• Keywords:
  Children Chlorpyrifos Cholinesterase Inhibitors Environmental Exposure Exposure Levels Food Health Effects Humans Metabolism Metabolites Models Pharmacodynamics Urinalysis

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• Publisher:
  University of Washington
• Document Type:
  Text
• Funding:
  Grant
• Genre:
  Abstract or Summary
• 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:
  1
• NIOSHTIC Number:
  nn:20050545
• Citation:
  Proceedings of Health and Safety in Western Agriculture: New Paths, November 11-13, 2008, Cle Elum, Washington. Seattle, WA, University of Washington, 2008 Nov; :1
• CAS Registry Number:
  Chlorpyrifos (CAS RN 2921-88-2)
• Federal Fiscal Year:
  2009
• NORA Priority Area:
  Agriculture, Forestry and Fishing
• Performing Organization:
  Battelle Pacific Northwest Laboratories
• Peer Reviewed:
  False
• Start Date:
  20060901
• Source Full Name:
  Proceedings of Health and Safety in Western Agriculture: New Paths, November 11-13, 2008, Cle Elum, Washington
• End Date:
  20170831
• Collection(s):
  National Institute for Occupational Safety and Health
• Main Document Checksum:
  urn:sha-512:4a8a58012d0775a273e6e44dfae67bb5187db1163634d0f865cecb68e4a91963d69d3d89871323ab299649ca393f02c8a276ff2fc2571c91d393d9352836541a
• Download URL:
  https://stacks.cdc.gov/view/cdc/210849/cdc_210849_DS1.pdf
• File Type:
  [PDF - 1.09 MB ]