title: Acute toluene exposure and rat visual function in proportion to momentary brain concentration.
abstract: Acute exposure to toluene was assessed in two experiments to determine the relationship between brain toluene concentration and changes in neurophysiological function. The concentration of toluene in brain tissue at the time of assessment was estimated using a physiologically based pharmacokinetic model. Brain neurophysiological function was measured using pattern-elicited visual evoked potentials (VEP) recorded from electrodes located over visual cortex of adult male Long-Evans rats. In the first experiment, VEPs were recorded before and during exposure to control air or toluene at 1000 ppm for 4 h, 2000 ppm for 2 h, 3000 ppm for 1.3 h, or 4000 ppm for 1 h. In the second experiment, VEPs were recorded during and after exposure to clean air or 3000 or 4000 ppm toluene. In both experiments, the response amplitude of the major spectral component of the VEP (F2 at twice the stimulus rate in steady-state responses) was reduced by toluene. A logistic function was fit to baseline-adjusted F2 amplitudes from the first experiment that described a significant relationship between brain toluene concentration and VEP amplitude deficits. In the second experiment, 3000 ppm caused equivalent VEP deficits during or after exposure as a function of estimated brain concentration, but 4000 ppm showed a rapid partial adaptation to the acute effects of toluene after exposure. In general, however, the neurophysiological deficits caused by acute toluene exposure could be described by estimates of the momentary concentration of toluene in the brain at the time of VEP evaluation.
authors.affiliation: Neurotoxicology Division, U.S. Environmental Protection Agency, Research Triangle Park, North Carolina 27711, USA. boyes.william@epa.gov
authors.forename: William K
authors.initials: WK
authors.lastname: Boyes
authors.forename: Mark
authors.initials: M
authors.lastname: Bercegeay
authors.forename: Quentin Todd
authors.initials: QT
authors.lastname: Krantz
authors.forename: Elaina M
authors.initials: EM
authors.lastname: Kenyon
authors.forename: Ambuja S
authors.initials: AS
authors.lastname: Bale
authors.forename: Timothy J
authors.initials: TJ
authors.lastname: Shafer
authors.forename: Philip J
authors.initials: PJ
authors.lastname: Bushnell
authors.forename: Vernon A
authors.initials: VA
authors.lastname: Benignus
mesh_terms: D000818:Animals; D001921:Brain / Q000378:metabolism*; D005074:Evoked Potentials, Visual / Q000187:drug effects*; D008297:Male; D008954:Models, Biological; D051381:Rats; D020318:Rats, Long-Evans; D014050:Toluene / Q000493:pharmacokinetics / Q000633:toxicity*; D014241:Trichloroethylene / Q000633:toxicity
chemical_list: D014241:Trichloroethylene; D014050:Toluene