models, particularly at lower concentrations of exposure. Where studies are available, information from human populations often relies on estimated rather than actual concentrations of exposure, making it difficult to evaluate risks to health. In addition, much of the literature related to trichloroethylene exposure in humans includes exposures to mixtures of solvents, so that it is difficult to evaluate the specific contribution of trichloroethylene to health outcomes.

ANIMAL TOXICITY

Acute Exposure

Experimental studies of acute exposures in rats have shown behavioral alterations across several functional domains at a range of concentrations that overlap with those associated with effects in humans. Most of these studies involved inhalation exposures. At higher concentrations of exposure (e.g., 1,000-4,000 ppm), reported effects include hearing loss, impaired oculomotor control, seizures, decreased wakefulness, and anesthetic effects such as lethargy and ataxia.

Auditory deficits have been observed in several studies at comparable exposure concentrations and in different strains of rats, attesting to the generality of the effects. These studies show auditory effects to occur primarily for the midfrequency tone range (Mattsson et al. 1993; Crofton and Zhao 1993; Jaspers et al. 1993; Rebert et al. 1993; Crofton et al. 1994). Studies have indicated the persistence of some adverse auditory effects, as evidenced 14 weeks postexpsoure to trichloroethylene at 4,000 ppm for 6 hr/day for 5 days (Crofton and Zhao 1993). Apparently, this outcome has not been studied after acute exposures of humans to high concentrations of trichloroethylene.

In rat models, high doses of trichloroethylene administered orally (2,500 mg/kg per day, 5 days per week for 10 weeks) result in morphologic changes in nerves, including alterations in myelination characteristics of the trigeminal nerve (Barret et al. 1991, 1992). These findings are consistent with reports of cranial nerve damage in humans (e.g., Cavanagh and Buxton 1989). A role was noted for the trichloroethylene degradation byproduct dichloroacetylene in eliciting these effects.

Effects on behavior at lower trichloroethylene concentrations in experimental studies have included impaired effortful motor response in rodents (measured by swimming performance) and decreased response of rats to avoid electric shock after a 4-hour exposure to trichloroethylene at 250 ppm (Kishi et al. 1993). The concentrations at which Kishi et al. (1993) observed effects are similar to those noted by Stewart et al. (1970) in humans reporting headaches, fatigue, and drowsiness after exposure to trichloroethylene



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