ToxSci Advance Access originally published online on November 1, 2006
Toxicological Sciences 2007 95(1):118-135; doi:10.1093/toxsci/kfl146
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Published by Oxford University Press 2006.
Inhalational Exposure to Carbonyl Sulfide Produces Altered Brainstem Auditory and Somatosensory-Evoked Potentials in Fischer 344N Rats
* Neurotoxicology Division, MD B105-05, NHEERL, ORD, USEPA, Research Triangle Park, North Carolina 27711
Pathology Associates Division of Charles River Laboratories, Durham, North Carolina 27713
Respiratory Toxicology, NIEHS, Research Triangle Park, North Carolina 27709
Laboratory of Experimental Pathology, NIEHS, Research Triangle Park, North Carolina 27709
1To whom correspondence should be addressed at 109 T.W. Alexander Drive, MD B105-05, NHEERL/NTD/NPTB, U.S. Environmental Protection Agency, Research Triangle Park, NC 27711. Fax: (919) 541-4849. E-mail: herr.david{at}epamail.epa.gov.
Received August 7, 2006; accepted September 12, 2006
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Abstract |
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Carbonyl sulfide (COS), a chemical listed by the original Clean Air Act, was tested for neurotoxicity by a National Institute of Environmental Health Sciences/National Toxicology Program and U.S. Environmental Protection Agency collaborative investigation. Previous studies demonstrated that COS produced cortical and brainstem lesions and altered auditory neurophysiological responses to click stimuli. This paper reports the results of expanded neurophysiological examinations that were an integral part of the previously published experiments (Morgan et al., 2004, Toxicol. Appl. Pharmacol. 200, 131–145; Sills et al., 2004, Toxicol. Pathol. 32, 1–10). Fisher 334N rats were exposed to 0, 200, 300, or 400 ppm COS for 6 h/day, 5 days/week for 12 weeks, or to 0, 300, or 400 ppm COS for 2 weeks using whole-body inhalation chambers. After treatment, the animals were studied using neurophysiological tests to examine: peripheral nerve function, somatosensory-evoked potentials (SEPs) (tail/hindlimb and facial cortical regions), brainstem auditory-evoked responses (BAERs), and visual flash–evoked potentials (2-week study). Additionally, the animals exposed for 2 weeks were examined using a functional observational battery (FOB) and response modification audiometry (RMA). Peripheral nerve function was not altered for any exposure scenario. Likewise, amplitudes of SEPs recorded from the cerebellum were not altered by treatment with COS. In contrast, amplitudes and latencies of SEPs recorded from cortical areas were altered after 12-week exposure to 400 ppm COS. The SEP waveforms were changed to a greater extent after forelimb stimulation than tail stimulation in the 2-week study. The most consistent findings were decreased amplitudes of BAER peaks associated with brainstem regions after exposure to 400 ppm COS. Additional BAER peaks were affected after 12 weeks, compared to 2 weeks of treatment, indicating that additional regions of the brainstem were damaged with longer exposures. The changes in BAERs were observed in the absence of altered auditory responsiveness in FOB or RMA. This series of experiments demonstrates that COS produces changes in brainstem auditory and cortical somatosensory neurophysiological responses that correlate with previously described histopathological damage.
Key Words: carbonyl sulfide; evoked potentials; BAER; SEP; CNAP; NCV.