Trichloroethylene (TCE)-induced Tencephalopathy:
Trichloroethylene (TCE) has been recognized as a neurotoxic solvent for over 50 years. Most commonly used to degrease machine parts, TCE has also been employed in the dry-cleaning industry, as a household cleaner, and as a constituent of lubricants and adhesives. It has been used as a short-acting anesthetic in dental and obstetric procedures. More recently, TCE has become one of the most extensively used solvents in Silicon Valley’s electronics industry for cleaning, stripping or degreasing.
Given this variety of applications, it is not surprising that about 3.5 million workers are exposed to TCE, with 100,000 of these exposed on a full-time basis. In 1978, NIOSH estimated that 67% of these workers were working with TCE under inadequate safety conditions.
The adverse health effects of TCE, which have been reviewed for two decades, include effects on the central and peripheral nervous systems, skin, liver, kidney, and heart. Trigeminal neuralgia (tic douloureux) secondary to TCE exposure was first noted in 1915; this observation led to unsuccessful attempts at curing this condition with the substance. TCE has been abused because of the euphoric effects that some people experience on inhaling the vapors.
Acute Nervous System Effects
In cases of acute or subacute intoxication with TCE, symptoms of eye and nose irritation, a feeling of drunkenness, dyspnea, nausea, headache, ataxia, in the worst cases eventually leading to myoclonus, confusion, somnolence, coma and convulsions have been described. These symptoms have been reproduced in human and animal experiments which required very high exposure levels, especially if the exposure duration was limited in time.
In the occupational setting, high airborne solvent concentrations, which may increase the risk of acute intoxication, can be encountered when the working conditions are related to confined spaces (e.g. cleaning of tanks or reactors) without personal protection, when large quantities are to be applied on broad surfaces, when the ventilation flow is in the direction of the breathing zone, or when TCE containing products are sprayed or applied in warm environments or are heated.
In the acute stage of intoxication no special clinical, neurophysiological (EEG, evoked potentials) or radiological signs (CT, MRI) have been found except if concomitant hypoxia was present, resulting in cerebral edema or infarction. Afterwards a discrete cortical-subcortical atrophy on CT or MRI scanning has been reported in some cases. Slowing of EEG activity has frequently been described in the acute stage. In such cases, persistent cognitive deficits have been shown to exist on neuropsychological testing shortly after the intoxication and are thought to predict a bad prognosis.
In conclusion, recovery after an acute intoxication with solvents can be uneventful, but cases of persisting mild to severe chronic encephalopathic syndromes have been described. Therefore, timely testing of basic neuropsychological functions (e.g. concentration ability, memory, psychomotor accuracy and speed, and conceptual ability and speed) is necessary for an adequate evaluation of these patients.
In contrast to the acute intoxication situation, the debate about chronic neurotoxic effects of daily low to moderate TCE exposures has not been settled. Some authors have reported that in occupational exposures not only the level of exposure, but also the duration of exposure is crucial because in healthy volunteers a much higher concentration was needed in acute exposure conditions to induce the same symptoms.
Organic psycho-syndromes such as toxic encephalopathy with concentration and memory difficulties, diminished psychomotor speed, decreased mental flexibility, mood changes, personality changes, diffuse pain, and sleeping difficulties have often been described in workers who experienced working conditions in which they experienced symptoms of acute intoxication. But, numerous cross-sectional studies in healthy subjects exposed to solvents such as TCE have shown dose-dependent subclinical effects on concentration, memory and psychomotor function, central and peripheral nerve conduction velocities, vestibular functioning and hearing. Even long-term exposure to low airborne exposure concentrations have been shown to produce slight pre-narcotic or irritation symptoms like headache, nausea, inappropriate laughing or angriness, dizziness, imbalance, and eye irritation.
In addition, as in the cases of acute intoxication, chronic exposure conditions may lead to cortical and subcortical atrophy on CT-scan and diffuse diminished blood flow on Single Photon Emission Tomography (SPECT) examination. The clinical picture described in these patients appears to be the same regardless of whether they were exposed to individual solvents such as TCE or to mixtures of solvents.
The odds ratio that exposed workers develop a neuropsychiatric disease has been estimated to be between 1.1 and 6.5 and it increases with increasing duration and intensity of the exposure.
Analysis of clinical cases reported in the literature indicated that psychomotor speed was the first neurobehavioral function to deteriorate after approximately ten years of exposure, followed by attention and memory.
Lindstrom et al. reported a group of 50 workers exposed to TCE for intervals of one month to 15 years. Nine of these workers displayed the organic psychosyndrome with toxic encephalopathy including memory disturbances, difficulties in understanding and changes in affective state.
Rasmussen et al. reported that the risk for developing an organic psychosyndrome among metal degreasers who worked primarily with TCE for an average of 11 years increases with increasing exposure. Diagnosis was made on the basis of symptom complaints and neuropsychological test performance. Effects remained significant after adjusting for age, premorbid intellectual level, alcohol abuse and other confounders.
Similar to what has been described with other solvents, progression of neurological manifestations of chronic TCE exposure have not been shown to progress after exposure had ceased; however, progression of mood disorders if present, has been described in the literature.
Mood problems such as depression are an essential part of the clinical picture of the organic psycho-syndrome. The WHO described mood changes as one of the first clinical signs of organic psycho-syndrome (OPS type 2a). Mood changes in combination with neurobehavioral performance deficits were classified as OPS type 2b.
Campagna et al. showed that mood changes were dose-dependent and developed independently from the other neurotoxic effects of solvent exposure.
Encephalopathy characterized by impaired short term memory, a sense of inebriation, irritability, and personality changes has been demonstrated in workers exposed to chronic, low level exposure due to a combination of respiratory and skin absorption. Some authors have reported that the metabolic products of TCE may contribute to some of the symptoms. Chloral hydrate, for example, an intermediary in TCE metabolism, is known to have hypnotic effects. Although skin absorption is not usually considered a major route of solvent exposure in man, profound and protracted skin contact with TCE has been associated with chronic neurological effects.
References are available upon request.