Science Inventory

BRAIN CHOLINESTERASE INHIBITION AND DEPRESSION OF THE PHOTIC AFTER DISCHARGE (PHAD) OF FLASH EVOKED POTENTIALS (FEPS) IN LONG EVANS RATS FOLLOWING ACUTE OR REPEATED EXPOSURES TO A MIXTURE OF CARBARYL AND PROPOXUR.

Citation:

MWANZA, J., D. F. LYKE, J. GRAFF, AND D. W. HERR. BRAIN CHOLINESTERASE INHIBITION AND DEPRESSION OF THE PHOTIC AFTER DISCHARGE (PHAD) OF FLASH EVOKED POTENTIALS (FEPS) IN LONG EVANS RATS FOLLOWING ACUTE OR REPEATED EXPOSURES TO A MIXTURE OF CARBARYL AND PROPOXUR. Presented at Society of Toxicology, Seattle, WA, March 16 - 20, 2008.

Impact/Purpose:

Carbaryl and propoxur are N-methyl carbamate pesticides (NMCs) which are part of the EPA’s cumulative risk assessments for NMCs. These NMCs inhibit cholinesterase (ChE) activity and may lead to cholinergic disruption of CNS function.

Description:

Carbaryl and propoxur are N-methyl carbamate pesticides (NMCs) which are part of the EPA’s cumulative risk assessments for NMCs. These NMCs inhibit cholinesterase (ChE) activity and may lead to cholinergic disruption of CNS function. We used decreases in the PhAD of FEPs to indicate altered CNS function. FEPs were recorded in male Long Evans rats (>60 days) following acute treatment with 0, 3, 10, 45 or 75 mg/kg or repeated administration (14 days) of 0, 3, 10, 30 or 45 mg/kg of the mixture (ratio propoxur:carbaryl = 1:1.45 ). One week before testing, rats were implanted with epidural electrodes. FEPs were recorded for 2 days to develop the PhAD. On the 3rd day, pupils were dilated (40 min) and rats dosed (30 min) before testing. Immediately after testing, rats were sacrificed, the brains removed, and stored at -80oC until determination of ChE levels by radiometric assay. Both acute and repeated treatments inhibited brain ChE activity to a similar extent. Three-45 mg/kg of the mixtures inhibited 14.7-56.4% (acute) and 11.3-53.5% (repeated) of brain ChE. Acute treatment with 75 mg/kg of the mixture resulted in 63.4% inhibition of ChE. The PhAD was significantly decreased after repeated exposures, and nearly significantly after acute treatment. Brain ChE levels significantly correlated with PhAD duration after both exposures. The early portion of the FEPs (peak N36) was not altered with either exposure duration. The results indicate that acute and repeated exposures to mixture of NMCs produced similar levels of brain ChE inhibition, and similar relationships between brain ChE levels and PhAD duration. They also support the conclusion that inhibition of brain ChE by NMCs disrupts the cortical processing related to the PhAD.

Record Details:

Record Type: DOCUMENT (PRESENTATION/ABSTRACT)
Product Published Date: 03/17/2008
Record Last Revised: 05/12/2008
OMB Category: Other
Record ID: 185643

Organization:

U.S. ENVIRONMENTAL PROTECTION AGENCY

OFFICE OF RESEARCH AND DEVELOPMENT

NATIONAL HEALTH AND ENVIRONMENTAL EFFECTS RESEARCH LABORATORY

NEUROTOXICOLOGY DIVISION

NEUROPHYSIOLOGICAL TOXICOLOGY BRANCH