Cholinesterase inhibition in chlorpyrifos workers: characterization of biomarkers of exposure and response in relation to urinary TCPy

Garabrant, David H., Aylward, Lesa L., Berent, Stanley, Chen, Qixuan, Timchalk, Charles, Burns, Carol J., Hays, Sean M. and Albers, James W. (2009) Cholinesterase inhibition in chlorpyrifos workers: characterization of biomarkers of exposure and response in relation to urinary TCPy. Journal of Exposure Science and Environmental Epidemiology, 19 7: 634-642. doi:10.1038/jes.2008.51

Author Garabrant, David H.
Aylward, Lesa L.
Berent, Stanley
Chen, Qixuan
Timchalk, Charles
Burns, Carol J.
Hays, Sean M.
Albers, James W.
Title Cholinesterase inhibition in chlorpyrifos workers: characterization of biomarkers of exposure and response in relation to urinary TCPy
Journal name Journal of Exposure Science and Environmental Epidemiology   Check publisher's open access policy
ISSN 1559-0631
Publication date 2009
Year available 2008
Sub-type Article (original research)
DOI 10.1038/jes.2008.51
Open Access Status Not yet assessed
Volume 19
Issue 7
Start page 634
End page 642
Total pages 9
Place of publication London, United Kingdom
Publisher Nature Publishing Group
Language eng
Formatted abstract
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 µg TCPy/g creatinine (Cr). Plasma BuChE activity, a non-adverse biomarker of exposure, was negatively related to urinary TCPy concentrations above approximately 110 µg 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 µg/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.
Keyword Chlorpyrifos
Cholinesterase inhibition
Dose-response assessment
Urinary 3;5;6-trichloro-2-pyridinol
Q-Index Code C1
Q-Index Status Provisional Code
Institutional Status Non-UQ

Document type: Journal Article
Sub-type: Article (original research)
Collection: National Research Centre for Environmental Toxicology Publications
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