In compliance with the Clean Air Act Section 211b for fuel and fuel additive registration, petroleum and oxygenate manufacturers have conducted comparative toxicology testing of evaporative emissions of gasoline alone, and gasoline plus ether and alcohol oxygenates. Here we present results from the neurotoxicity component of this program. The functional observation battery (FOB) with the addition of motor activity (MA) testing, hemotoxylin and eosin staining of brain tissue sections, and brain regional analysis of glial fibrillary acidic protein (GFAP) were used to assess behavioral changes, neuropathology and gliosis, respectively, following inhalation exposure to the test agents. Seven vapor condensates of gasoline (GVC) or gasoline+ether [MTBE (G/MTBE), ethyl t-butyl ether (G/ETBE), t-amyl methyl ether (G/TAME), diisopropyl ether (G/DIPE)] or alchohol [ethanol (G/EtOH), t-butyl alcohol (G/TBA)] oxygenates were evaluated. Sprague-Dawley rats of both sexes were exposed to the test agents (2000-20, 000 mg/m 3) by inhalation for 13 weeks (6 hrs/day, 5 days/week). FOB and MA were conducted on non-exposure days, at least 16 days post-initiation of exposures; neuropathology and GFAP analyses were conducted at the study termination (13 weeks). A recovery group was included to monitor resolution of behavioral changes. FOB and MA data for all agents, except G/TBA, were negative. G/TBA behavioral effects resolved during recovery. Neuropathology was negative for all groups. Analyses of GFAP revealed multi-brain region increases (as great as 150% of air controls) limited largely to males of the G/EtOH group. Small changes (mostly increases) in GFAP were observed for other test agents but these effects were not consistent across sex, brain region or exposure concentration. The results are consistent with the incidence of a mild gliosis in males of the G/EtOH group. Results of these studies will be used for comparative risk assessments of gasoline/oxygenate blends.
The Toxicologist. Society of Toxicology 43nd Annual Meeting and ToxExpo, March 21-25, 2004, Baltimore, Maryland