title: Inhalational exposure to carbonyl sulfide produces altered brainstem auditory and somatosensory-evoked potentials in Fischer 344N rats.
abstract: 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.
authors.affiliation: Neurotoxicology Division, MD B105-05, NHEERL, ORD, USEPA, Research Triangle Park, North Carolina 27711, USA. herr.david@epamail.epa.gov
authors.forename: David W
authors.initials: DW
authors.lastname: Herr
authors.forename: Jaimie E
authors.initials: JE
authors.lastname: Graff
authors.forename: Virginia C
authors.initials: VC
authors.lastname: Moser
authors.forename: Kevin M
authors.initials: KM
authors.lastname: Crofton
authors.forename: Peter B
authors.initials: PB
authors.lastname: Little
authors.forename: Daniel L
authors.initials: DL
authors.lastname: Morgan
authors.forename: Robert C
authors.initials: RC
authors.lastname: Sills
mesh_terms: D000818:Animals; D001522:Behavior, Animal / Q000187:drug effects; D001831:Body Temperature / Q000187:drug effects; D001933:Brain Stem / Q000187:drug effects* / Q000473:pathology / Q000503:physiopathology; D003106:Colon; D004305:Dose-Response Relationship, Drug; D004785:Environmental Pollutants / Q000633:toxicity*; D016057:Evoked Potentials, Auditory, Brain Stem / Q000187:drug effects*; D005073:Evoked Potentials, Somatosensory / Q000187:drug effects*; D005074:Evoked Potentials, Visual / Q000187:drug effects; D019570:Inhalation Exposure; D051381:Rats; D011916:Rats, Inbred F344; D011930:Reaction Time / Q000187:drug effects; D013216:Reflex, Startle / Q000187:drug effects; D013461:Sulfur Oxides / Q000633:toxicity*; D013997:Time Factors
chemical_list: D004785:Environmental Pollutants; D013461:Sulfur Oxides; C010063:carbonyl sulfide