Comparative Pharmacokinetics of the Organophosphorus Insecticide Chlorpyrifos and its Major Metabolites Diethylphosphate, Diethylthiophosphate and 3,5,6-Trichloro-2-pyridinol in the Rat

Journal Article · Tue Jul 31 00:00:00 EDT 2007 · Toxicology

DOI:https://doi.org/10.1016/j.tox.2007.05.007· OSTI ID:915708

Timchalk, Chuck; Busby, Andrea L; Campbell, James A; Needham, Larry L; Barr, Dana

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 140 μmol/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 1-3 h post-dosing. In the case of DEP and TCPy virtually all the administered dose was recovered in the urine by 72 h post-dosing, suggesting negligible, if any, metabolism; whereas with DETP, ~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 ± 3 μmol) > DETP (14 ± 2 μmol) > DEP (1.4 ± 0.7 μmol). 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.

• Research Organization: Pacific Northwest National Lab. (PNNL), Richland, WA (United States)
• Sponsoring Organization: USDOE
• DOE Contract Number: AC05-76RL01830
• OSTI ID: 915708
• Report Number(s): PNNL-SA-55442; TXCYAC; 400412000; TRN: US200816%%34
• Journal Information: Toxicology, Vol. 237, Issue 1-3; ISSN 0300-483X
• Country of Publication: United States
• Language: English

Related Subjects

63 RADIATION, THERMAL, AND OTHER ENVIRONMENTAL POLLUTANT EFFECTS ON LIVING ORGANISMS AND BIOLOGICAL MATERIALS
RATS
BIODEGRADATION
BLOOD
INSECTICIDES
KINETICS
METABOLISM
METABOLITES
BIOLOGICAL INDICATORS
MONITORING
ORAL ADMINISTRATION
URINE
PHARMACOLOGY
pharmacokinetics
chlorpyrifos
diethylthiophosphate
diethylphosphate
trichlorpyridinol