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SUBCHRONIC TOXICITY OF INHALED TOLUENE IN RATS: OXIDATIVE STRESS MARKERS IN BRAIN.
Citation:
MOORE-SMITH, D. A., T. E. SAMSAM, P. A. EVANSKY, P. J. BUSHNELL, AND PRASADA RAO S. KODAVANTI. SUBCHRONIC TOXICITY OF INHALED TOLUENE IN RATS: OXIDATIVE STRESS MARKERS IN BRAIN. Presented at Society of Toxicology, Seattle, WA, March 16 - 20, 2008.
Impact/Purpose:
A sub-chronic inhalation study with multiple endpoints was conducted to seek effects of the VOC toluene in rats.
Description:
The effects of long-term exposure to volatile organic compounds (VOCs), which is of concern to the EPA, are poorly understood, primarily due to insufficient information about human exposure and unreliable animal models. A sub-chronic inhalation study with multiple endpoints was conducted to seek effects of the VOC toluene in rats. Adult male Long-Evans rats (N=240) were exposed to toluene vapor at mean ± SD concentrations of 0 ± 0, 10 ± 1.4, 97 ± 7, or 995 ± 43 ppm for 6h/d, 5 d/week for 13 weeks. 24 hours after the last exposure, 6 animals per group were sacrificed and brains were taken on ice. Cortex, hippocampus, and striatum were dissected, quick frozen on dry ice, and stored at -80oC until analysis of oxidative stress parameters. The brain regions were homogenized in 20 mM Tris buffer (pH 7.4) and centrifuged at 8000 g for 20 min. The supernatants were assayed for total aconitase activity, glutathione (GSH) peroxidase, GSSG reductase, GSH transferase, glutamylcysteine synthetase, superoxide dismutase, and NADPH quinone oxidoreductase-1 using kits from Oxis International Inc. The results showed that sub-chronic inhalation of toluene by rats affected several oxidative stress markers. Total aconitase activity (involved in maintaining iron homeostasis and an indicator of DNA damage) was inhibited in striatum, increased in hippocampus, and unchanged in cortex. The effect of toluene exposure on superoxide dismutase, GSSG reductase and glutamylcysteine synthetase was greater in striatum than in the other brain regions. These results indicate that subchronic toluene exposure may induce oxidative stress in the CNS, which could be a molecular basis for its neurotoxicy. (This abstract does not necessarily reflect USEPA policy).