The Ototoxicity of Trichloroethylene: Extrapolation and Relevance of High-Concentration, Short-Duration Animal Exposure Data

Abstract

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-m³stainless 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 dB15 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.