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Toluene Inhalation Exposure for 13 Weeks Causes Persistent Changes in Electroretinograms of Long-Evans Rats
Citation:
Boyes, W., M. Bercegeay, L. Degn, T. Beasley, P. Evansky, J. Mwanza, A. Geller, C. Pinckney, M. Nork, AND P. Bushnell. Toluene Inhalation Exposure for 13 Weeks Causes Persistent Changes in Electroretinograms of Long-Evans Rats. NEUROTOXICOLOGY. Elsevier B.V., Amsterdam, Netherlands, 53:257-270, (2016).
Impact/Purpose:
Impaired visual function has been reported in human populations exposed to organic solvents, as described in several review articles (Benignus et al 2005, Fox 2015, Fox & Boyes 2013, Geller & Hudnell 1997, Gobba 2000, Gobba 2003, Gobba & Cavalieri 2003, Iregren et al 2002, Kishi et al 2000, Lomax et al 2004, Paramei et al 2004). The visual deficits reported have included impaired color discrimination, impaired visual contrast sensitivity, and several other measures.
Description:
Studies of humans chronically exposed to volatile organic solvents have reported impaired visual functions, including low contrast sensitivity and reduced color discrimination. These reports, however, lacked confirmation from controlled laboratory experiments. To address this question experimentally, we examined visual function by recording visual evoked potentials (VEP) and/or electroretinograms (ERG) from four sets of rats exposed repeatedly to toluene. In addition, eyes of the rats were examined with an ophthalmoscope and some of the retinal tissues were evaluated for rod and M-cone photoreceptor immunohistochemistry. The first study examined rats following exposure to 0, 10, 100 or 1000 ppm toluene by inhalation (6 hr/d, 5 d/wk) for 13 weeks. One week after the termination of exposure, the rats were implanted with chronically indwelling electrodes and the following week pattern-elicited VEPs were recorded. VEP amplitudes were not significantly changed by toluene exposure. Four to five weeks after completion of exposure, rats were dark-adapted overnight, anesthetized, and several sets of electroretinograms (ERG) were recorded. In dark-adapted ERGs recorded over a 5-log (cd-s/m2) range of flash luminance, b-wave amplitudes were significantly reduced at high stimulus luminance values in rats previously exposed to 1000 ppm toluene. A second set of rats, exposed concurrently with the first set, was tested approximately one year after the termination of 13 weeks of exposure to toluene. Again, dark-adapted ERG b-wave amplitudes were reduced at high stimulus luminance values in rats previously exposed to 1000 ppm toluene. A third set of rats was exposed to the same concentrations of toluene for only 4 weeks, and a fourth set of rats exposed to 0 or 1000 ppm toluene for 4 weeks were tested approximately 1 year after the completion of exposure. No statist ically significant reductions of ERG b-wave amplitude were observed in either set of rats exposed for 4 weeks. No significant changes were observed in ERG a-wave amplitude or latency, b-wave latency, UV- or green-flicker ERGs, or in photopic flash ERGs. There were no changes in the density of rod or M-cone photoreceptors. The ERG b-wave reflects the firing patterns of on-bipolar cells. The reductions of b-wave amplitude after 13 weeks of exposure and persisting for 1 year suggest that alterations may have occurred in the inner nuclear layer of the retina, where the bipolar cells reside, or the outer or inner plexiform layers where the bipolar cells make synaptic connections. These data provide experimental evidence that repeated exposure to toluene may lead to subtle persistent changes in visual function. The fact that toluene affected ERGs, but not VEPs, suggests that elements in the rat retina may be more sensit ive to organic solvent exposure than the rat visual cortex.
