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Toxicology and senescence: Baseline variability and toluene effects on the motor function of aging brown Norway rats.
Citation:
MACPHAIL, R. C., J. D. FARMER, AND K. JAREMA. Toxicology and senescence: Baseline variability and toluene effects on the motor function of aging brown Norway rats. Presented at Society of Toxicology, Seattle, WA, March 16 - 20, 2008.
Impact/Purpose:
Research was undertaken to quantify senescence-related changes in motor activity and the effect of toluene.
Description:
The rapidly expanding population of older adults raises concern in EPA over aging-related vulnerability to environmental exposures. Deficits in motor function are frequent with advancing age. An increase in interindividual variability is also commonly accepted. Increased variability due to aging could complicate vulnerability assessment. Research was therefore undertaken to quantify senescence-related changes in motor activity and the effect of toluene. Male Brown Norway rats (from NIA) were tested as young (4-5 mo), middle-age (12-13 mo) or old (24-25 mo) adults. Motor activity was recorded in a photocell chamber during 30-min sessions. Each rat received corn oil (4 ml/kg) and toluene (1000 mg/kg) p.o., 30 min before testing. Toluene effects were expressed relative to each rat’s vehicle-control data. Combining three experiments yielded group sizes of 18-21 animals. Under baseline conditions, motor activity (horizontal and vertical) decreased with age. Interindividual variability was greatest in the old rats, and least in middle-age rats. Toluene increased horizontal activity by approximately 45% in young and middle-age rats, and by about 150% in the old rats. Variability in the effect of toluene was greatest in the old rats, and equivalent in the two younger groups. Toluene effects on vertical activity (decreases) were irregular, with no clear pattern related to age. Further comparison of toluene effects on horizontal activity, using z-scores based on young rats as the reference group, resulted in means and SDs of 0.0 and 1.0 (young), 0.1 and 1.0 (middle age), and 1.7 and 3.0 (old). With a threshold for toluene’s adverse effect (hyperactivity) set at z=1.65, the increased risk of hyperactivity was estimated to be 22% for the middle-age rats and in excess of 900% for the oldest rats. These results provide quantitative support for both the increased variability and enhanced vulnerability of senescent organisms to toxic substances. This is an abstract of a proposed presentation; the information does not necessarily reflect Agency policy.