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Acute Exposure to Perchlorethylene alters Rat Visual Evoked Potentials in Relation to Brain Concentration
BOYES, W. K., M. S. BERCEGEAY, W. M. OSHIRO, TODD T. KRANTZ, E. M. KENYON, P. J. BUSHNELL, AND V. A. BENIGNUS. Acute Exposure to Perchlorethylene alters Rat Visual Evoked Potentials in Relation to Brain Concentration. TOXICOLOGICAL SCIENCES. Society of Toxicology, RESTON, VA, 108(1):159-172, (2009).
Perchloroethylene is a widely used industrial compound. Among its common uses are dry cleaning, metal cleaning and degreasing, and textile processing. It is of regulatory concern as an air pollutant, water contaminant and constituent of hazardous waste sites. Among the populations of concern are residents of apartment buildings that have co-located dry cleaners. Air in those apartments can be contaminated with perchloroethylene, and two epidemiological studies have shown subtle visual disturbances in the residents of such buildings. This manuscript demonstrates acute impairments in neurophysiological measures of visual function in rats breathing different concentrations of perchloroethylene, with the onset of deficits occurring within minutes of initial exposure. Similar to other volatile organic compounds evaluated, the magnitude of neurophysiological impairment could be related to the momentary concentration of perchloroethylene in the brain, regardless of external air concentration or the duration of exposure. This information provides a risk assessment tool that could be used to estimate quantitatively the magnitude of acute neurological impairments to be expected in people exposed to perchloroethylene from a variety of acute exposure scenarios.
These experiments sought to establish a dose-effect relationship between the concentration of perchloroethylene (PCE) in brain tissue and concurrent changes in visual function. A physiologically-based pharmacokinetic (PBPK) model was implemented to predict concentrations of PCE in the brains of adult Long-Evans rats following inhalation exposure. The model was evaluated for performance against tissue concentrations from exposed rats, and also against data from the published scientific literature. Visual function was assessed using steady-state pattern-elicited visual evoked potentials (VEPs) recorded from rats during exposure to air or PCE in two experiments with concentrations of PCE ranging from 250 – 4000 ppm. VEP waveforms were submitted to a spectral analysis in which the major response component, F2, occurring at twice the visual stimulation rate, was reduced in amplitude by PCE exposure. The F2 amplitudes were reduced by exposure to PCE. The F2 amplitudes were transformed to an effect magnitude scale ranging from 0 (no effect) to 1 (maximum possible effect) and a logistical function was fit to the transformed values as a function of estimated concurrent brain PCE concentrations. The resultant function described a dose-response relationship between brain PCE concentration and changes in visual function, with an ED10 value of approximately 0.684 mg/l and an ED50 value of approximately 46.5 mg/l. The results confirmed that visual function was disrupted by acute exposure to PCE, and the PBPK model and logistic model together constitute predictive functions capable of making quantitative estimates of the magnitude of deficit to be expected for any given exposure scenario.