The Effect of Plasma Lipids on the Pharmacokinetics of Chlorpyrifos and the Impact on Interpretation of Blood Biomonitoring Data

Details

• Personal Author:
  Bartels MJ ; Lowe ER ; Marty MS ; Mattsson JL ; Poet TS ; Rick DL ; Timchalk C
• Description:
  Lipophilic molecules, like chlorpyrifos (CPF), present a special problem for interpretation of biomonitoring data because both the environmental dose of CPF and the physiological (pregnancy, diet, etc.) or pathological levels of blood lipids will affect the concentrations of CPF measured in blood. The objective of this study was to investigate the distribution of CPF between plasma and tissues when lipid levels are altered in late pregnancy. CPF was sequestered more in the low-density lipid fraction of the blood during the late stages of gestation in the rat and returned to nonpregnant patterns in the dam after birth. Plasma partitioning of CPF increased with increases in plasma lipid levels and the increased partitioning of CPF into plasma lipids resulted in less CPF in other tissue compartments. Gavage dosing with corn oil also increased plasma lipids that led to a moderate increase of CPF partitioning into the plasma. To mechanistically investigate the potential pharmacokinetic effects of blood lipid changes, an existing CPF physiologically based pharmacokinetic/pharmacodynamic model for rats and humans was modified to account for altered lipid-tissue partition coefficients and for major physiological and biochemical changes of pregnancy. The model indicated that plasma CPF levels are expected to be proportional to the well-known changes in plasma lipids during gestation. There is a rapidly growing literature on the relationship of lipid profiles with different disease conditions and on birth outcomes. Increased blood concentrations of lipophilic chemicals like CPF may point to altered lipid status, as well as possibly higher levels of exposure. Thus, proper interpretation of blood biomonitoring data of lipophilic chemicals requires a careful consideration of blood lipids. [Description provided by NIOSH]
• Subjects:
  Coal Coal Mining Geology Mining Occupational Health Safety
• Keywords:
  Animals Biochemical Effects Biomonitoring Blood Blood Plasma Chlorpyrifos Diet Environmental Monitoring Humans Laboratory Animals Lipids Models Molecular Biology Pathology Pharmacodynamics Physiological Factors Pregnancy Women

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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:
  258-272
• Volume:
  108
• Issue:
  2
• NIOSHTIC Number:
  nn:20050531
• Citation:
  Toxicol Sci 2009 Apr; 108(2):258-272
• Contact Point Address:
  Michael J. Bartels, Toxicology & Environmental Research and Consulting, The Dow Chemical Company, Midland, Michigan 48674
• Email:
  mjbartels@dow.com
• 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:
  True
• Start Date:
  20060901
• Source Full Name:
  Toxicological Sciences
• End Date:
  20170831
• Collection(s):
  National Institute for Occupational Safety and Health
• Main Document Checksum:
  urn:sha-512:c9c425a24d400c88e766e489add82337a158acbc5dedff3ccee0439dd4ed69d6041fd183319a33470fc30dd693bb5a39e0918d23d4eb060811df93eb8975bb7d
• Download URL:
  https://stacks.cdc.gov/view/cdc/210839/cdc_210839_DS1.pdf
• File Type:
  [PDF - 961.32 KB ]