Assessing the Human Health Risks of Trichloroethylene Key Scientific Issues (2006) / Chapter Skim
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6 Neurotoxicity
6 Neurotoxicity
Pages 213-232
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Surprisingly, little information exists on the effects of more protracted exposures on the central nervous system, either in humans or in experimental 213
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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.
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NEUROTOXICITY 21 for 7 hr/day for 5 days.
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studied the effects of trichloroethylene on rats exposed during development (gestation and lactation) at concentrations of 312, 625, and 1,250 mg/L in drinking water.
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NEUROTOXICITY 21 Studies of subchronic exposure to trichloroethylene in rats reported after the EPA (2001b) draft risk assessment include that of Poon et al.
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Although these findings suggest no residual learning deficits after trichloroethylene exposure, the differential effects of amphetamine in control versus trichloroethylene-treated animals could indicate residual effects on brain dopamine neurotransmitter systems after trichloroethylene exposure. Dopamine pathways of the central nervous system are critical for cognitive and executive functions.
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The report described (but did not quantify) transient postdosing effects in rats that are consistent with previous reports in human and experimental exposures (lethargy, ataxia, and convulsions)
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and EPA (2001b) focused on studies in rats because most human studies involved chronic exposures.
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In addition, the LOAELs from four different animal studies examining nervous system effects show a high degree of correspondence, ranging from 20 to 50 ppm, with corresponding human equivalent concentrations of 7-16 ppm. Among the human studies, the report by Ruijten et al.
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(1994) in rats after subchronic inhalation exposures (LOAEL of 50 ppm with human pharmacokinetic adjusted value of 9 ppm and a human pharmacokinetic adjusted BMD10 value of 5 ppm)
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. Tests of behavior, visual contrast sensitivity, and mood were carried out for estimated exposures of 5, >5-10, >10-15, and >15 ppb, with 5 ppb representing the maximum contaminant level for drinking water as defined by the EPA Office of Drinking Water.
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For these reasons, including these data in the trichloroethylene risk assessment should be considered cautiously. One interesting aspect of this study, however, if reliability of the trichloroethylene exposure assessments is assumed, is the strong interactions that emerged between trichloroethylene exposure and alcohol consumption.
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(1990) cited improvements rather than impairments in learning, here measured using a spatial learning paradigm in young male rats exposed to trichloroethylene in drinking water.
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(1999) of oral exposure to dichloroacetic acid, a metabolite that can be formed via mixed function oxidase metabolism of trichloroethylene, does include some comparisons of weanling versus adult rats.
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This study also showed that, instead, the estimated peak blood concentration of trichloroethylene at the time of testing accurately predicted the magnitude of effect on visual function and on signal detection (these neurotoxic effects reflect momentary tissue concentrations of trichloroethylene)
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Indeed, significant amounts of TaClo (approximately 200 ng per 10 mL samples) were detected in both serum and clot in Parkinson's disease patients that had been treated for several days with 500 mg of chloral hydrate (a metabolite of trichloroethylene)
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. Studies in rats showed changes in heart rate and wakefulness at a human pharmacokinetic adjusted LOAEL of 9 ppm (Arito et al.
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(1999) examining one metabolite of trichloroethylene, dichloroacetic acid, where the evidence in support of enhanced susceptibility of younger rats is limited.
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to those doses. One would predict that this enhanced toxicity should generalize to other behavioral and neurological consequences of trichloroethylene as well, because functionally it represents a higher dose to the brain, particularly if peak blood trichloroethylene concentrations are critical to adverse effects (Boyes et al.
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, it is possible that trichloroethylene may contribute as a risk factor to other neurodegenerative and behavioral diseases or dysfunctions, acting in conjunction with other risk modifiers that may include genetic background (P-450 polymorphisms) and lifestyle factors (e.g., alcohol consumption)
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