Cholinesterase Inhibition in Chlorpyrifos Workers: Characterization of Biomarkers of Exposure and Response in Relation to Urinary TCPy

Details

• Personal Author:
  Albers JW ; Aylward LL ; Berent S ; Burns CJ ; Chen Q ; Garabrant, David H. ; Hays SM ; Timchalk C
• Description:
  The objective of this study was to evaluate the quantitative relation between measured red blood cell acetylcholinesterase (RBC AChE) and plasma butyrylcholinesterase (BuChE) activities with exposure to chlorpyrifos (CPF) as assessed by measurement of urinary 3,5,6-trichloro-2-pyridinol (TCPy) in a study group of workers occupationally exposed in the manufacture of CPF and a referent group of chemical manufacturing workers. Measures of plasma BuChE and RBC AChE activity and urinary TCPy concentration collected over a year-long study (1999-2000) in CPF-exposed workers (n=53) and referents (n=60) were analyzed using linear mixed models to characterize exposure-response relationships. Intraindividual variability in cholinesterase measures was compared between CPF-exposed workers and referents. Urinary TCPy concentrations in CPF workers were substantially elevated compared to referents, with median and 95th percentile concentrations during typical employment conditions 10-fold and more than 30-fold higher, respectively, than corresponding measures in the referents. Intraindividual variability in cholinesterase activities was substantial, with 17% of unexposed referents experiencing one or more plasma BuChE measures more than 20% below baseline over a year of repeated, periodic measurements. RBC AChE activity, an early biomarker of effect, was unrelated to urinary TCPy concentration over the entire range of exposure, up to 1000 microg TCPy/g creatinine (Cr). Plasma BuChE activity, a non-adverse biomarker of exposure, was negatively related to urinary TCPy concentrations above approximately 110 microg TCPy/g Cr. No-effect levels for inhibition of plasma BuChE and RBC AChE corresponding to absorbed doses of CPF of approximately 5 and greater than 50 microg/kg/day, respectively, were identified. These findings are consistent with previous no-effect level determinations for ChE inhibition in humans and suggest that general population CPF exposure levels are substantially below the identified no-effect levels. The dose-response relationships observed in this study are consistent with predictions from the previously published physiologically based pharmacokinetic/pharmacodynamic model for CPF. Intraindividual variability in measured cholinesterase activities in referents was substantial, suggesting that ongoing monitoring programs may have a substantial rate of false positives. [Description provided by NIOSH]
• Subjects:
  Biochemistry Biomarkers Chemistry Environmental Monitoring Hazardous Substances Hypersensitivity Manufacturing And Industrial Facilities Occupational Exposure Occupational Health Risk Assessment Risk Factors Safety Urine

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• Keywords:
  Author Keywords: Cholinesterase Inhibition Biochemical-analysis Biochemical-tests Biodynamics Biological-effects Biological-monitoring Biostatistics Chemical-factory-workers Chemical-hypersensitivity Chemical-reactions Chlorpyrifos Dose-response Dose-response Assessment Exposure-assessment Exposure-levels Exposure-methods Occupational-exposure Occupational-health Pharmacodynamics Quantitative-analysis Risk-analysis Risk-factors Statistical-analysis Toxic-effects Toxins Urinary 3,5,6-trichloro-2-pyridinol Urine-chemistry

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• ISSN:
  1559-0631
• Document Type:
  Text
• Funding:
  Grant
• Genre:
  Journal Article
• Place as Subject:
  Michigan ; OSHA Region 10 ; OSHA Region 3 ; OSHA Region 5 ; Virginia ; Washington
• CIO:
  National Institute for Occupational Safety and Health (NIOSH)
• Topic:
  Workplace Safety & Health
• Location:
  North America
• Volume:
  9
• Issue:
  7
• NIOSHTIC Number:
  nn:20036560
• Citation:
  J Expo Sci Environ Epidemiol 2009 Nov; 9(7):634-642
• Contact Point Address:
  Dr. Lesa L. Aylward, Summit Toxicology, LLP, 6343 Carolyn Drive, Falls Church, VA 22044
• Email:
  laylward@summittoxicology.com
• 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:
  Journal of Exposure Science and Environmental Epidemiology
• End Date:
  20050929
• Collection(s):
  National Institute for Occupational Safety and Health
• Main Document Checksum:
  urn:sha-512:aaac5b9cca338d8f04c1edd3473b35e440d0115fa60275653826522875a314d5358225d44d7b4ddba95d9a97cd0a3538d6476082f2e01e7c4f4cfd73b67ac7ba
• Download URL:
  https://stacks.cdc.gov/view/cdc/187929/cdc_187929_DS1.pdf
• File Type:
  [PDF - 341.50 KB ]