Science Inventory

Dose-response and time-course of neurotoxicity and tissue concentrations of carbaryl in Brown Norway rats from preweaning to senescence.

Citation:

MOSER, V. C. Dose-response and time-course of neurotoxicity and tissue concentrations of carbaryl in Brown Norway rats from preweaning to senescence. Presented at Society of Toxicology (SOT) Annual Meeting, San Francisco, CA, March 11 - 15, 2012.

Impact/Purpose:

We systematically compared the dose-response (3, 7.5, 15,22.5 mg/kg) and time-course (3 or 15 mg/kg at 30, 60, 120, 240 min) of acute effects of carbaryl (oral gavage) in preweanling (postnatal day, PND, 18) and adult male Brown Norway rats ranging from adolescence to senescence (1, 4, 12,24 mo). Motor activity (MA), brain and RBC cholinesterase (ChE) activity, and brain and plasma carbaryl concentrations were measured in the same animals.

Description:

Factors impacting sensitivity to chemicals across life stages include toxicokinetic and toxicodynamic changes. We systematically compared the dose-response (3, 7.5, 15,22.5 mg/kg) and time-course (3 or 15 mg/kg at 30, 60, 120, 240 min) of acute effects of carbaryl (oral gavage) in preweanling (postnatal day, PND, 18) and adult male Brown Norway rats ranging from adolescence to senescence (1, 4, 12,24 mo). Motor activity (MA), brain and RBC cholinesterase (ChE) activity, and brain and plasma carbaryl concentrations were measured in the same animals. At the time of peak effect (40 min), PND 18 rats were the most sensitive to the brain ChE-inhibiting effects of carbaryl, but 12-and 24-mo rats showed more MA depression even at similar levels of brain ChE inhibition. Time-course data showed that MA depression reached a maximum earlier in the 1-and 4-mo rats compared to the other ages, and recovery was also faster; slowest recovery and maximal effects were seen in the 24-mo rats. The recovery of brain ChE inhibition varied with age only after 15 mg/kg, whereas recovery following 3 mg/kg as well as RBC ChE inhibition (both doses) was similar across ages. Brain ChE inhibition generally tracked brain carbaryl concentrations regardless of the time after dosing, but not so with RBC ChE and plasma carbaryl levels. The lowest carbaryl concentrations across all treatments were measured in the 1-and 4-mo rats, and despite similarities in brain ChE inhibition, brain carbaryl levels were greatest in PND 18 and 24-mo rats across times and doses. The higher concentrations agreed with the greater MA depression observed in the older rats but not with MA changes in PND 18 pups. Thus, in the dose-response and time-course, there were dissociations between both brain ChE inhibition and carbaryl concentrations, and the magnitude as well as recovery of MA changes. Age-related differences in the carbaryl tissue concentrations were evident but were not fully consistent with brain or RBC ChE inhibition across doses and time. This abstract does not reflect US EPA policy.

Record Details:

Record Type: DOCUMENT (PRESENTATION/ABSTRACT)
Product Published Date: 03/15/2012
Record Last Revised: 11/29/2012
OMB Category: Other
Record ID: 238628