Skip directly to search Skip directly to A to Z list Skip directly to page options Skip directly to site content

NIOSHTIC-2 Publications Search

Search Results

Comparative pharmacokinetics of chlorpyrifos versus its major metabolites following oral administration in the rat.

Authors
Busby-Hjerpe-AL; Campbell-JA; Smith-JN; Lee-S; Poet-TS; Barr-DB; Timchalk-C
Source
Toxicology 2010 Jan; 268(1-2):55-63
NIOSHTIC No.
20036473
Abstract
Chlorpyrifos (CPF) is a commonly used diethylphosphorothionate organophosphorus (OP) insecticide. Diethylphosphate (DEP), diethylthiophosphate (DETP) and 3,5,6-trichloro-2-pyridinol (TCPy) are products of both in vivo metabolism and environmental degradation of CPF and are routinely measured in urine as biomarkers of exposure. Hence, urinary biomonitoring of TCPy, DEP and DETP may be reflective of an individual's contact with both the parent pesticide and exposure to these metabolites in the environment. In the current study, simultaneous dosing of 13C- or 2H-isotopically labeled CPF (13C-labeled CPF, 5 13C on the TCPy ring; or 2H-labeled CPF, diethyl-D10 (deuterium labeled) on the side chain) were exploited to directly compare the pharmacokinetics and metabolism of CPF with TCPy, and DETP. The key objective in the current study was to quantitatively evaluate the pharmacokinetics of the individual metabolites relative to their formation following a dose of CPF. Individual metabolites were co-administered (oral gavage) with the parent compound at equal molar doses (14 micromol/kg; approximately 5 mg/kg CPF). Major differences in the pharmacokinetics between CPF and metabolite doses were observed within the first 3h of exposure, due to the required metabolism of CPF to initially form TCPy and DETP. Nonetheless, once a substantial amount of CPF has been metabolized (> or =3h post-dosing) pharmacokinetics for both treatment groups and metabolites were very comparable. Urinary excretion rates for orally administered TCPy and DETP relative to 13C-CPF or (2)H-CPF derived 13C-TCPy and 2H-DETP were consistent with blood pharmacokinetics, and the urinary clearance of metabolite dosed groups were comparable with the results for the 13C- and 2H-CPF groups. Since the pharmacokinetics of the individual metabolites were not modified by co-exposure to CPF; it suggests that environmental exposure to low dose mixtures of pesticides and metabolites will not impact their pharmacokinetics.
Keywords
Biological-effects; Biological-factors; Biological-systems; Biomarkers; Chemical-hypersensitivity; Chemical-reactions; Environmental-exposure; Exposure-assessment; Exposure-levels; Exposure-limits; Exposure-methods; Insecticides; In-vivo-studies; Laboratory-animals; Pesticides; Pharmacodynamics; Quantitative-analysis; Author Keywords: Chlorpyrifos; Diethylthiophosphate; Trichloropyridinol; Pharmacokinetics
Contact
Charles Timchalk, Battelle, Pacific Northwest Division, P.O. Box 999, Richland, WA 99354
CODEN
TXCYAC
CAS No.
2921-88-2
Publication Date
20100131
Document Type
Journal Article
Funding Amount
246279
Funding Type
Grant
Fiscal Year
2010
NTIS Accession No.
NTIS Price
Identifying No.
Grant-Number-R01-OH-003629; Grant-Number-R01-OH-008173
Issue of Publication
1-2
ISSN
0300-483X
Priority Area
Research Tools and Approaches: Exposure Assessment Methods; Agriculture, Forestry and Fishing
Source Name
Toxicology
State
WA
Performing Organization
Battelle Memorial Institute, Richland, Washington
TOP