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Comparative pharmacokinetics of the organophosphorus insecticide chlorpyrifos and its major metabolites diethylphosphate, diethylthiophosphate and 3,5,6-trichloro-2-pyridinol in the rat.

Authors
Timchalk-C; Busby-A; Campbell-JA; Needham-LL; Barr-DB
Source
Toxicology 2007 Jul; 237(1-3):145-157
NIOSHTIC No.
20032567
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 metabolism and of environmental degradation of CPF and are routinely measured in urine as biomarkers of exposure. However, because these same chemicals can result from metabolism or by biodegradation, monitoring total urinary metabolite levels may be reflective of not only an individual's contact with the parent pesticide, but also exposure with the metabolites, which are present in the environment. The objective of the current study was to compare the pharmacokinetics of orally administered DEP, DETP and TCPy with their kinetics following oral dosing with the parent insecticide CPF in the rat. Groups of rats were orally administered CPF, DEP, TCPy or DETP at doses of 140mumol/kg body weight, and the time-courses of the metabolites were evaluated in blood and urine. Following oral administration, all three metabolites were well absorbed with peak blood concentrations being attained between 1 and 3h post-dosing. In the case of DEP and TCPy virtually all the administered dose was recovered in the urine by 72h post-dosing, suggesting negligible, if any, metabolism; whereas with DETP, approximately 50% of the orally administered dose was recovered in the urine. The CPF oral dose was likewise rapidly absorbed and metabolized to DEP, TCPy and DETP, with the distribution of metabolites in the urine followed the order: TCPy (22+/-3mumol)>DETP (14+/-2mumol)>DEP (1.4+/-0.7mumol). Based upon the total amount of TCPy detected in the urine a minimum of 63% of the oral CPF dose was absorbed. These studies support the hypotheses that DEP, DETP and TCPy present in the environment can be readily absorbed and eliminated in the urine of rats and potentially humans.
Keywords
Insecticides; Laboratory-animals; Animal-studies; Metabolism; Models; Pharmacodynamics; Biodynamics; Biochemical-analysis; Environmental-contamination; Environmental-factors; Environmental-exposure; Pesticides; Urine-chemistry; Biomarkers; Metabolic-rate; Metabolism; Blood-tests; Blood-samples; Organo-phosphorus-pesticides
Contact
Charles Timchalk, Pacific Northwest National Laboratory, 902 Battelle Blvd, PO Box 999, Richland, WA 99352
CODEN
TXCYAC
CAS No.
2524-04-1
Publication Date
20070731
Document Type
Journal Article
Email Address
charles.timchalk@pnl.gov
Funding Amount
246279
Funding Type
Grant
Fiscal Year
2007
NTIS Accession No.
NTIS Price
Identifying No.
Grant-Number-R01-OH-008173
Issue of Publication
1-3
ISSN
0300-483X
Priority Area
Agriculture, Forestry and Fishing
Source Name
Toxicology
State
WA
Performing Organization
Battelle Pacific Northwest Laboratories
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