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Toluene effects on the motor activity of adolescent, young-adult, middle-age and senescent male Brown Norway rats.
MACPHAIL, R. C., J. D. FARMER, AND K. JAREMA. Toluene effects on the motor activity of adolescent, young-adult, middle-age and senescent male Brown Norway rats. NEUROTOXICOLOGY. Intox Press, Inc, Little Rock, AR, 33(1):111-8, (2012).
In support of EPA's Aging Initiative, this work was undertaken to characterize and compare baseline motor function (locomotor activity) and the effect of toluene in senescent Brown Norway rats and in several younger ages of rat. Results showed that baseline motor function decreased with age. Senescent rats were considerably more sensitive to toluene than were younger ages of rat. Variability in both baseline activity and toluene effects was greatest in the senescent rats. These results underscore the importance of assessing toxicant sensitivity in an aging rat model, in evaluating toxicant effects at multiple life stages, and quantifying interindividual differences in toxicant response. These results also emphasize the need for improved approaches to risk assessment that specifically incorporate response variability.
Life stage is an important risk factor for toxicity. Children and aging adults, for example, are more susceptible to certain chemicals than are young adults. In comparison to children, relatively little is known about susceptibility in older adults. Additionally, few studies have compared toxicant susceptibility across a broad range of life stages. Results are presented for behavioral evaluations of male Brown Norway rats obtained as adolescents (1 month), or young (4 months), middle-age (12 months) and senescent (24 months) adults. Motor activity was evaluated in photocell devices during 30-min sessions. Age-related baseline characteristics and sensitivity to toluene (0, 300, 650, or 1000mg/kg, p.o.) were determined. In Experiment 1, young-adult, middle-age and senescent rats were treated with corn-oil vehicle before five weekly test sessions. Baselines of horizontal and vertical activity decreased with age, but each age-group's averages remained stable across weeks of testing. Baseline activity of older rats was more variable than that of the young adults; older rats were also more variable individually from week to week. Toluene (1000mg/kg) increased horizontal activity proportionately more in senescent rats (ca. 300% of control) than in middle-age or young-adult rats (ca.145-175% of control). Experiment 2 established toluene dose-effect functions in individual adolescent, young-adult, middle-age and senescent rats; each rat received all treatments, counterbalanced across four weekly sessions. Toluene produced dose-related increases in horizontal activity that increased proportionately with age. Experiment 3 replicated the effects of toluene (1000mg/kg) in Experiment 1, showing that toluene-induced increases in horizontal activity were greatest in the oldest rats. Collectively, the results show that aging increased susceptibility to toluene and also increased variability in toluene response. Given the rapid growth of the aged population, further research is needed on aging-related susceptibility to environmental contaminants.