title: Acute inhalation of 2,2,4-trimethylpentane alters visual evoked potentials and signal detection behavior in rats.
abstract: The volatile organic compound 2,2,4-trimethylpentane (TMP, "isooctane") is a constituent of gasoline for which the current health effects data are insufficient to permit the US Environmental Protection Agency to conduct a risk assessment. The potential neurological impairment from acute inhalation exposure to TMP was evaluated in adult male Long-Evans rats using both electrophysiological and behavioral assessments. Visual evoked potentials (VEPs) were recorded from rats viewing modulated visual patterns (0.16 cycles per degree visual angle (cpd), 60% contrast, 4.55Hz appear/disappear). Rats (n=7-10/dose) were exposed to TMP vapors in concentrations of 0, 500, or 1000 ppm for 60-min. A VEP was recorded before exposure and at 10 min intervals during exposure and also for 60 min after exposure terminated. The spectral amplitude of the frequency-double component (F2) was significantly reduced after exposure to TMP. In behavioral assessments, rats (n=14) performed an appetitively motivated visual signal detection task while breathing 0, 500, 1500, 1000, 2000, or 2500 ppm TMP for 62 min. Slight reductions in accuracy of performance were observed at the 2500 ppm concentration. Concentrations of TMP in the brain were estimated using a physiologically based pharmacokinetic (PBPK) model to be less than 0.2mM after 62 min at 2500 ppm. Together these data demonstrate that TMP, like other volatile organic substances, impairs neurological function during acute inhalation exposure and that the small magnitude of the observed effects is consistent with the low concentrations of this hydrocarbon that were estimated to reach the CNS.
authors.affiliation: National Health and Environmental Effects Research Laboratory, Office of Research and Development, U.S. Environmental Protection Agency, Research Triangle Park, NC 27711, USA. boyes.william@epa.gov
authors.forename: William K
authors.initials: WK
authors.lastname: Boyes
authors.forename: Wendy M
authors.initials: WM
authors.lastname: Oshiro
authors.forename: Hisham
authors.initials: H
authors.lastname: El-Masri
authors.forename: Laura L
authors.initials: LL
authors.lastname: Degn
authors.forename: Mark
authors.initials: M
authors.lastname: Bercegeay
authors.forename: Q Todd
authors.initials: QT
authors.lastname: Krantz
authors.forename: Philip J
authors.initials: PJ
authors.lastname: Bushnell
mesh_terms: D000704:Analysis of Variance; D000818:Animals; D001522:Behavior, Animal / Q000187:drug effects; D004305:Dose-Response Relationship, Drug; D004569:Electroencephalography; D005074:Evoked Potentials, Visual / Q000187:drug effects*; D019570:Inhalation Exposure; D008297:Male; D009795:Octanes / Q000494:pharmacology*; D010775:Photic Stimulation / Q000379:methods; D051381:Rats; D020318:Rats, Long-Evans; D011930:Reaction Time / Q000187:drug effects; D017603:Signal Detection, Psychological / Q000187:drug effects*; D013997:Time Factors
chemical_list: D009795:Octanes; C045798:2,2,4-trimethylpentane