© 1997 Oxford University Press
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The Ototoxicity of Trichloroethylene: Extrapolation and Relevance of High-Concentration, Short-Duration Animal Exposure Data1
*Neurotoxicology Division, National Health and Environmental Effects Research Laboratory, U.S. Environmental Protection Agency Research Triangle Park, North Carolina 27711
ManTech Sciences, Inc. Research Triangle Park, North Carolina 27709
Received January 6, 1997; accepted May 9, 1997
Inhalation exposure to high concentrations of 1,1,2-trichloroethylene (TCE) has been shown to damage hearing in the mid-frequency range in the rat. The present study directly evaluated the adequacy of high-concentration, short-term exposures to TCE for predicting the neurotoxicity produced by longer duration exposures. Adult male Long-Evans rats (n = 10–12 per group) were exposed to TCE via inhalation (whole body) in 1-m3 stainless steel flow-through chambers for 6 hr/day, 5 days/week. The following exposures were used: 1 day (4000–8000 ppm), 1 week (1000–4000 ppm), 4 weeks (800–3200 ppm), and 13 weeks (800–3200 ppm). Air-only exposed animals served as controls. Auditory thresholds were determined for a 16-kHz tone 3–5 weeks after exposure using reflex modification audiometry. Results replicated previous findings of a hearing loss at 16 kHz for all exposure durations. The dBl5 concentrations (concentration that increases thresholds by 15 dB) for 16-kHz thresholds were 6218, 2992, 2592, and 2160 ppm for the 1-day, 1-week, 4-week and 13-week exposures, respectively. These data demonstrate that the ototoxicity of TCE was less than that predicted by a strict concentration × time relationship. These data also demonstrate that simple models of extrapolation (i.e., C × t = k, Haber's Law) overestimate the potency of TCE when extrapolating from short-duration to longer-duration exposures. Furthermore, these data suggest that, relative to ambient or occupational exposures, the ototoxicity of TCE in the rat is a high-concentration effect.