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ToxSci Advance Access published online on December 19, 2008
Toxicological Sciences, doi:10.1093/toxsci/kfn265
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Published by Oxford University Press 2008.

Acute Perchloroethylene Exposure Alters Rat Visual Evoked Potentials in Relation to Brain Concentrations

William K. Boyes*, Mark Bercegeay*, Wendy M. Oshiro*, Q. Todd Krantz{dagger}, Elaina M. Kenyon{dagger}, Philip J. Bushnell* and Vernon A. Benignus{ddagger}

* Neurotoxicology Division {dagger} Experimental Toxicology Division {ddagger} Human Studies Division, National Health and Environmental Effects Research Laboratory, Office of Research and Development, U.S. Environmental Protection Agency, Research Triangle Park, North Carolina

Address for correspondence and reprints: William K. Boyes, B105-05, Neurotoxicology Division, U.S. Environmental Protection Agency, Research Triangle Park, NC 27711, Telephone: 919-541-7538, Fax: 919-541-4849, Email: boyes.william{at}epa.gov

Received November 4, 2008; revision received December 13, 2008; accepted December 13, 2008


  Abstract

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 (n = 40) and 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 (total n = 84) 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 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 could be used to make quantitative estimates of the magnitude of deficit to be expected for any given inhalation exposure scenario.

Key Words: neurotoxicity; PBPK model; volatile organic compound; organic solvent; visual evoked potential.


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