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NEUROTOXICITY OF CARBARYL IN THE AGING BROWN NORWAY RAT: EFFECTS ON CORE TEMPERATURE AND MOTOR ACTIVITY.
GORDON, C. J., P. BECKER, AND C. M. MACK. NEUROTOXICITY OF CARBARYL IN THE AGING BROWN NORWAY RAT: EFFECTS ON CORE TEMPERATURE AND MOTOR ACTIVITY. Presented at Society of Toxicology, Charlotte, NC, March 25 - 29, 2007.
The US EPA is pursuing a variety of research efforts to assess the susceptibility of the aged to neurotoxicants. The BN strain is a popular animal model for aging studies but there is a need for improved methods of monitoring their physiological responses to neurotoxicants over the animal's life span. This study used radiotelemetry to follow longitudinal changes in Tc and MA, and sensitivity to carbaryl in 16 male rats surgically implanted with radiotransmitters (Data Sciences Int.). Tc and MA were recorded at 5 min intervals for 7 days in undisturbed animals. Monitoring was initiated at 90 days of age and was repeated every other month. Following the baseline monitoring, rats were dosed with carbaryl (25 mg/kg; po) or the corn oil vehicle. Tc and MA data in the undisturbed animals were ensembled into a single 24 hr period for statistical analysis. At the time of writing, data have been collected in animals at ages of 90, 150, and 210 days. Aging has quantitative and qualitative effects on the circadian rhythm of Tc and MA and on intra-subject variation. Aging has been associated with a slight reduction in Tc; rats at 90, 150, and 210 days had a mean Tc of 37.23, 37.15, and 37.11 °C. MA has not paralleled the changes in Tc. Mean MA was 1.88 and 1.57 cts/min in 90 and 150 day old rats but increased to 1.64 cts/min in the 210 day old animals. The thermoregulatory response to carbaryl has also changed with aging. The first dosing with carbaryl led to a prolonged hypothermic response and little effect on MA that recovered within 24 hr. The peak decrease in Tc following carbaryl was -1.9, -1.9, and -0.7 °C at ages of 90, 150, and 210 days of age, respectively. Baseline Tc and MA and their response to carbaryl will be followed at 60 day intervals for at least two years. The data will provide a framework to develop methods for using the BN rat as a model of susceptibility to neurotoxic agents in the aged. This is an abstract of a proposed presentation and does not necessarily reflect EPA policy.