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Age-related brain cholinesterase inhibition kinetics following in vitro incubation with chlorpyrifos-oxon and diazinon-oxon.

Authors
Kousba-AA; Poet-TS; Timchalk-C
Source
Toxicol Sci 2007 Jan; 95(1):147-155
NIOSHTIC No.
20031530
Abstract
Chlorpyrifos and diazinon are two commonly used organophosphorus insecticides (OPs), and their primary mechanism of action involves the inhibition of acetylcholinesterase by their metabolites chlorpyrifos-oxon (CPO) and diazinon-oxon (DZO), respectively. The study objectives were to assess the in vitro age-related inhibition kinetics of neonatal rat brain cholinesterase (ChE) for CPO and DZO by estimating the bimolecular inhibitory rate constant (k(i)) values. Brain ChE inhibition and k(i) values following CPO and DZO incubation with neonatal Sprague-Dawley rat brain homogenates were determined at postnatal day (PND) 5, 12, and 17 and compared with the corresponding inhibition and k(i) values obtained in the adult rat. A modified Ellman method was utilized for measuring the ChE activity. CPO caused a greater ChE inhibition than DZO as evidenced from the estimated k(i) values of both compounds. Neonatal brain ChE inhibition kinetics exhibited a marked age-related sensitivity to CPO, with the order of ChE inhibition being PND 5 > PND 7 > PND 17 with k(i) values of 0.95, 0.50, and 0.22 nM(-1)hr(-1), respectively. In contrast, DZO ChE inhibition was not age related in the neonatal brain, and the estimated k(i) value at all PND ages was 0.02 nM(-1)hr(-1). These results demonstrated an age- and OP-selective inhibition of rat brain ChE, which may be critically important in understanding the potential sensitivity of juveniles to specific OPs exposures.
Keywords
Pharmacodynamics; Laboratory-animals; Animals; Animal-studies; Organo-phosphorus-pesticides; Insecticides; Toxic-effects; Exposure-levels; Exposure-assessment; Age-groups; Brain-function
Contact
Department of Pharmaceutical Property Assessments, TargeGen Inc., San Diego, California 92121
CODEN
TOSCF2
CAS No.
2921-88-2; 333-41-5
Publication Date
20070101
Document Type
Journal Article
Email Address
akousba@targegen.com
Funding Amount
246279
Funding Type
Grant
Fiscal Year
2007
NTIS Accession No.
NTIS Price
Identifying No.
Grant-Number-R01-OH-003629
Issue of Publication
1
ISSN
1096-6080
Priority Area
Research Tools and Approaches: Exposure Assessment Methods
Source Name
Toxicological Sciences
State
WA
Performing Organization
Battelle Memorial Institute, Richland, Washington
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