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SUBCHRONIC TOXICITY OF INHALED TOLUENE IN RATS: IMMUNOLOGY, CARDIAC GENE EXPRESSION AND MARKERS OF OXIDATIVE STRESS.
Citation:
BUSHNELL, P. J., U. P. KODAVANTI, P. A. EVANSKY, R. W. LUEBKE, C. B. COPELAND, AND J. DEWITT. SUBCHRONIC TOXICITY OF INHALED TOLUENE IN RATS: IMMUNOLOGY, CARDIAC GENE EXPRESSION AND MARKERS OF OXIDATIVE STRESS. Presented at Society of Toxicology, Charlotte, NC, March 25 - 29, 2007.
Description:
The health effects of long-term exposure to volatile organic compounds (VOCs) are poorly understood, due primarily to insufficient human exposure data and inconsistent animal models. To develop a rodent model of long-term exposure to VOCs, a sub-chronic inhalation study with multiple endpoints was conducted in rats exposed to toluene, a prevalent VOC. We report here that toluene did not affect immune function or gene expression of ion channel proteins, heme oxygenase (HO-1), or markers of oxidative stress in cardiac tissue. Effects on nervous system functions appear in separate reports. Adult male Long-Evans rats were exposed to toluene vapor at 0 ± 0, 10 ± 1.4, 97 ± 7, or 995 ± 43 ppm (mean ± SD) for 6h/d, 5 d/wk for 13 weeks. During the final week of exposure, subgroups of rats from each concentration were immunized with sheep red blood cells (SRBCs) to assess antibody synthesis; separate groups were sensitized to bovine serum albumin (BSA) to elicit delayed-type hypersensitivity (DTH) responses. Cardiac gene expression was assayed using real time PCR for HO-1, L-type calcium channel (L-Ca), KV1, connexin-40 and sodium channel protein-6 (SCP6). Activities of enzymes sensitive to inhibition by oxidative stress were also analyzed in mitochondrial and cytosolic fractions. Titers of SRBC-specific IgM and IgG antibodies and DTH responses to BSA were not affected by toluene. No consistent exposure-related changes were noted in cardiac gene expression or activity of enzymes associated with oxidative stress. These results indicate that sub-chronic inhalation of toluene in rats did not affect humoral or cellular immunity, did not change the expression of a number of genes coding for important cardiac proteins, and did not induce oxidative stress in cardiac tissue. These findings contrast with significant changes in CNS function observed in other rats in this study. This report does not reflect EPA policy.