Trichloroethylene ototoxicity: evidence for a cochlear origin.
Trichloroethylene (TCE) is known to produce an unusual pattern of hearing impairment in laboratory animals marked by a preferential loss of threshold sensitivity at midfrequencies. The purpose of this research was to determine whether the TCE-induced auditory deficit results from cochlear dysfunction. Adult Long Evans hooded rats were exposed via inhalation to either 0 (clean air) or 4000 ppm TCE (6 h/day for 5 days). Auditory thresholds for 1-40 kHz tones were determined 3 weeks after exposure using reflex modification audiometry (RMA; n = 12/group). Cochlear electropotentials were measured during subsequent testing (n = 3-10/group) 5 to 7 weeks after exposure, including thresholds for cochlear action potentials (CAP) and the 1-microV cochlear microphonic for 2-40 kHz tones, and the N1 amplitude intensity function (40-90 dB SPL). Cochlear histopathology was assessed in midmodiolar preparations of a separate set of animals, exposed as before (n = 4/group). RMA testing confirmed a TCE-induced loss in midfrequency threshold sensitivity (8 and 16 kHz). CAP thresholds were elevated at midfrequencies (8 and 16 kHz) among TCE-treated subjects, along with a suppression of the N1 amplitude from 50 to 90 dB SPL. The cochlear microphonic, a nonpropagated ac potential generated largely by the outer hair cells, was not affected by the TCE treatment. Cochlear histopathology revealed a loss of spiral ganglion cells that was significant in the middle turn, but not in the basal turn. There was an inconsistent loss of hair cells among treated subjects. The data suggest strongly that the behaviorally determined loss in auditory function can be accounted for by a cochlear impairment and that the spiral ganglion cell may be a prominent target of TCE.
Fechter
L D
LD
Toxicology Program, The University of Oklahoma College of Pharmacy, Oklahoma City, Oklahoma, USA.
Liu
Y
Y
Herr
D W
DW
Crofton
K M
KM
D000818:Animals; D003051:Cochlea / Q000187:drug effects* / Q000473:pathology; D006311:Hearing Disorders / Q000139:chemically induced* / Q000473:pathology; D008297:Male; D051381:Rats; D012997:Solvents / Q000633:toxicity*; D014241:Trichloroethylene / Q000633:toxicity*
D012997:Solvents; D014241:Trichloroethylene