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6 Neurotoxicity
Pages 213-232

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From page 213...
... Surprisingly, little information exists on the effects of more protracted exposures on the central nervous system, either in humans or in experimental 213
From page 214...
... 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.
From page 215...
... NEUROTOXICITY 21 for 7 hr/day for 5 days.
From page 216...
... 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.
From page 217...
... NEUROTOXICITY 21 Studies of subchronic exposure to trichloroethylene in rats reported after the EPA (2001b) draft risk assessment include that of Poon et al.
From page 218...
... 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.
From page 219...
... 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)
From page 220...
... As the trichloroethylene concentrations increase, dizziness, loss of facial sensation and unconsciousness can occur. With acute exposures to high concentrations (albeit highly unspecified [e.g., 1,000 ppm and above; anesthetic use was approximately 2,000 ppm]
From page 221...
... 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.
From page 222...
... . These reports are further supported by early studies reporting symptoms of drowsiness, fatigue, headaches, and nausea in response to occupational inhalation exposures to trichloroethylene over a mean of 7-8 years, with human pharmacokinetic adjusted LOAELs using RfC methodology for a category 3 gas, extrathoracic effects (EPA 1994b)
From page 223...
... (2003) based on residence in a community where the drinking water had been contaminated with trichloroethylene and related chemicals between 1981 and 1986 (Rocky Mountain Arsenal Superfund site)
From page 224...
... 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.
From page 225...
... (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.
From page 226...
... (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.
From page 227...
... 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)
From page 228...
... , a potent dopaminergic neurotoxin that can be formed endogenously after exposure to the sedative chloral hydrate or after exposure to trichloroethylene. As the authors note, trichloroethylene has an estimated half-life in humans in venous blood of 21.7 hours, sufficient for the appropriate in vivo condensation reactions that would be involved in TaClo formation.
From page 229...
... . Studies in rats showed changes in heart rate and wakefulness at a human pharmacokinetic adjusted LOAEL of 9 ppm (Arito et al.
From page 230...
... (1999) examining one metabolite of trichloroethylene, dichloroacetic acid, where the evidence in support of enhanced susceptibility of younger rats is limited.
From page 231...
... 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.
From page 232...
... , 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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