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Acute and Subchronic Toxicity of Inhaled Toluene in Male Long-Evans Rats: Oxidative Stress Markers in Brain
Kodavanti, P., J. Royland, D. Moore-Smith, J. Beas, J. Richards, T. Beasley, P. Evansky, AND P. Bushnell. Acute and Subchronic Toxicity of Inhaled Toluene in Male Long-Evans Rats: Oxidative Stress Markers in Brain. NEUROTOXICOLOGY. Elsevier B.V., Amsterdam, Netherlands, 51:10-19, (2015).
Work was done prior to RAP Codes per Dr. Prasda Kodavanti" Volatile organic compounds (VOCs) are ubiquitous in our environment and continue to pose a significant health problem in industrial nations. Toluene is a representative of the large class of solvents present in many commercial products, including adhesives, paint thinners, and cleaning agents (Low et al., 1988). Toluene also is used to produce benzene and is used as a solvent. Exposure to toluene may occur from breathing ambient or indoor air affected by such sources. The ubiquity of toluene creates a high potential for societal cost if long-term exposure results in toxicity (ATSDR, 1994).
The effects of exposure to volatile organic compounds (VOCs), which are of concern to the EPA, are poorly understood, in part because of insufficient characterization of how human exposure duration impacts VOC effects. Two inhalation studies with multiple endpoints, one acute and one subchronic, were conducted to seek effects of the VOC, toluene, in rats and to compare the effects between acute and subchronic exposures. Adult male Long-Evans rats were exposed to toluene vapor (n = 6 per group) at a concentration of 0 or l 019 ± 14 ppm for 6 h in the acute study and at 0 ± 0, 10 ± 1.4, 97 ± 7, or 995 ± 43 ppm for 6 h/d, 5 d/week for 13 weeksin the subchronic study. For the acute study, brains were dissected on ice within 30 min of the end of exposure, while for the subchronic study, brains were dissected 18 h after the last exposure. Frontal cortex, hippocampus, cerebellum, and striatum were assayed for a variety of oxidative stress (OS) parameters including total aconitase (TA), protein carbonyls, glutathione peroxidase (GPX), glutathione reductase (GRD), glutathione transferase (GST), y-glutamylcysteine synthetase (GCS), superoxide dismutase (SOD), total antioxidants (TAS), NADPH quinone oxidoreductase- 1 (NQO1 ), and NADH ubiquinone reductase (UBIQ-RD) activities using commercially available kits. Following acute exposure, UBIQ-RD, GCS and GRD were increased significantly only in the cerebellum, while TAS was increased in frontal cortex. On the other hand, subchronic exposure affected several OS markers including increases in NQO1 and UBIQ-RD. The effect of subchronic toluene exposure on SOD and TAS was greater in the striatum than in the other brain regions. TA activity (involved in maintaining iron homeostasis and an indicator of DNA damage) was inhibited in striatum and cerebellum, increased in hippocampus, and unchanged in frontal cortex. Protein carbonyls increased significantly in both the frontal cortex and cerebellum. In general, the results showed that acute exposures to toluene affected OS parameters to a lesser extent that did subchronic exposure. These results suggest that toluene exposure OS in the brain and this may be a component of an adverse outcome pathway for some of the neurotoxic effects reported following toluene exposure.exposure to toluene affected OS parameters to a lesser extent than did subchronic exposure. These results suggest that toluene exposure induces OS in the brain and this may be a component of an adverse outcome pathway for some of the neurotoxic effects reported following toluene exposure.
Record Details:Record Type: DOCUMENT (JOURNAL/PEER REVIEWED JOURNAL)
Organization:U.S. ENVIRONMENTAL PROTECTION AGENCY
OFFICE OF RESEARCH AND DEVELOPMENT
NATIONAL HEALTH AND ENVIRONMENTAL EFFECTS RESEARCH LABORATORY
TOXICOLOGY ASSESSMENT DIVISION