Evaluation and Diagnosis

After completing this section, you will be able to Describe possible clinical symptoms and signs in patients exposed to TCE.

When considering the human health effects of TCE, it is important to make a distinction between occupational exposures to relatively high levels by inhalation and general environmental exposures to low levels in drinking water and ambient air.

Symptoms and signs potentially associated with TCE exposure are nonspecific, making a careful medical and exposure history essential to diagnosis.

The initial history and physical examination of patients potentially exposed to TCE can be used to

• determine possible sources and pathways of exposure to TCE,
• detect symptoms and signs attributable to TCE exposure, and
• reveal history of any preexisting or underlying condition(s) that might complicate the diagnostic and clinical approach to the patient.

An exposure history should be part of the patient history. (ATSDR has developed CSEMs on “Taking an Exposure History” and “Taking a Pediatric Exposure History.” To view these CSEMs, and others, go to http://www.atsdr.cdc.gov/csem/.) Taking an exposure history might enable physicians to

• make more accurate diagnoses,
• influence the course of disease by stopping current exposure,
• prevent disease in others by avoiding future exposure, and
• prompt workplace evaluations and worker protection.

An exposure history should cover occupational and non-occupational TCE exposure risks. If you suspect a temporal association between symptoms and exposure to certain products, try to identify the specific chemical ingredients involved.

Environmental exposure history

An environmental exposure history (non-occupational) for TCE includes

• type of water supply,
• location and duration of residence,
• proximity to industry and National Priorities List sites, and
• patient’s hobbies.

Gather any additional information regarding history of exposure to other potentially toxic agents, including medications and alcohol.

Occupational exposure history

An occupational history should be routinely obtained. It should include items such as

• company name and location
• job title
• employment dates
• description of chemical processes encountered
• known toxic agents used
• personal protective equipment (PPE) used
• workplace investigations
• complaints of co-workers
• medical monitoring

Medical history

Medical history and review of body systems should include assessment of current and past diagnoses or symptoms of diseases of the

• neurologic,
• hepatic,
• renal, and
• reproductive systems.

Also consider the association between solvent exposure and health conditions (Rom, 2007), such as

• glomerulonephritis,
• contact dermatitis,
• cognitive impairment, and
• peripheral neuropathy.

Identify the patient’s complaints in terms of

• onset,
• duration,
• frequency, and
• intensity.

Note the time of patient’s last exposure to a suspected chemical. A temporal relationship between onset of symptoms and work or other activity could provide important diagnostic clues.

When performing a physical exam, you might see subclinical, delayed, or individual variability in the initial presentation.

Record vital signs, noting any abnormalities of heart rate or rhythm. Examine the head, eyes, ears, nose, and throat, noting any inflammation or irritation.

Inspect the skin for signs of dermatitis and defatting changes, especially in the hands. Exam findings might include

• redness,
• drying,
• cracking, or
• fissuring.

Chest examination should include assessment of the heart and lungs. Abdominal exam should include palpation for liver and spleen size (i.e., hepatomegaly, hepatosplenomegaly, etc.) and tenderness.

Conduct a mental status examination to evaluate

• alertness,
• orientation,
• cognition, and
• short-term memory.

Assess nervous system function by evaluating

• proprioception,
• deep tendon reflexes,
• cranial nerves,
• cerebellar function (nystagmus, finger-nose test, rapid alternating movements, heel-shin test),
• motor strength,
• gait,
• postural stability (Romberg test), and
• sensitivity to vibration, light touch, and pin prick.

The onset, intensity, and duration of symptoms can vary among identically exposed persons. Many factors influence the variability of toxicity, including respiratory rate, target organ sensitivity, body fat content, and general health. Central nervous system (CNS) symptoms can be similar to those of ethanol inebriation.

With inhalation of high concentrations, TCE causes initial CNS excitation, followed by CNS depression. Depending on the duration and intensity of exposure, signs and symptoms can include

• ataxia,
• bronchial irritation,
• confusion,
• dizziness,
• drowsiness,
• dyspnea,
• euphoria,
• fatal cardiac dysrhythmias,
• fatigue,
• headache,
• lethargy,
• light-headedness,
• pulmonary edema,
• renal and hepatic damage,
• respiratory depression,
• seizures,
• stupor, and
• visual disturbances.

Coma and respiratory depression might occur after prolonged, high-level inhalation exposure (i.e., >2,000 ppm). Serious ventricular arrhythmias can develop up to 24 hours after large TCE ingestions (ATSDR, 2019).

Effects from ingestion of moderate to large amounts of TCE include

• abdominal pain,
• circulatory collapse,
• diarrhea,
• dizziness,
• dysphagia,
• dysrhythmias,
• hallucinations or distorted perceptions,
• headache,
• incoordination,
• jaundice,
• nausea,
• paresthesia,
• partial paralysis,
• somnolence, and
• vomiting.

TCE is a skin irritant and can cause defatting dermatitis of the skin. Systemic sclerosis (scleroderma) has been linked with TCE exposure. Dermal absorption is not likely to be significant if dermatitis is prevented. Vasodilation (“degreasers flush”) and malaise (Stewart & Hake, 1974) recur in workers who drink ethanol after repeated exposure to TCE.

The clinician should keep in mind that, for patients with acute high-dose exposure,

• Respiratory depression and mental status changes are serious effects of acute high-dose TCE exposure. The adequacy of ventilation should be carefully assessed, especially among patients with decreased levels of consciousness. End-tidal capnography and pulse oximetry monitoring might be helpful, if available.
• Because of possible arrhythmias and other cardiovascular effects, consider performing a 12-lead electrocardiogram, frequent evaluation of vital signs, and continuous cardiac monitoring. This might be especially important among patients with preexisting cardiovascular disease.
• Because hepatic injury can occur, liver function tests should be performed.

The symptoms seen in humans in cases of long-term exposure were similar to those seen in acute exposure, but occurred in more extreme and persistent forms (Fan, 1988; Kleinfeld, 1954). The World Health Organization noted that chronic effects such as disturbance of the nervous system can occur after prolonged exposure to TCE concentrations of about 100 ppm (the current OSHA 8-hour permissible exposure limit [PEL]) (WHO, 1985).

Reported neurological effects associated with chronic workplace exposure to TCE have included nonspecific symptoms such as

• ataxia,
• decreased appetite,
• dizziness,
• emotional instability,
• fatigue,
• headache,
• impaired judgment,
• memory loss,
• sleep disturbances, and
• weakness.

Although some CNS symptoms disappear within several weeks after cessation of chronic occupational exposure, other CNS adverse health effects, such as memory loss and mood swings, can persist in persons who have been exposed to TCE for long periods (ATSDR, 2019).

Persistent neurological symptoms suggest the possibility of psychiatric disorders and should also prompt a search for exposure to neurotoxicants, such as alcohol and other drugs of abuse.

TCE may be measured to confirm TCE exposure. Keep in mind that although a TCE test might show recent exposure, correlating a TCE level to specific health effects is not possible. Significant exposure to TCE can result in elevated values of routine laboratory tests, including renal and liver function tests, although they are not specific to TCE exposure.

TCE: Directly testing for TCE in the blood can be used for either immediate exposure or chronic exposure. However, multiple factors can influence these results, including time when the sample was taken, total body fat, activity level, and enzyme activity of aldehyde and alcohol dehydrogenase (Waksman & Phillips, 2004). Detectable plasma levels of TCE in persons without occupational exposure are approximately 0.01 micrograms per deciliter (mg/dL) to 0.13 mg/dL.

TCE can be detected in the breath and urine up to 16 hours after exposure. It is worth noting that although breath testing conducted soon after exposure can confirm exposure, it is not widely available, so the usefulness is probably limited.

TCE metabolites: Although TCE disappears rapidly from the blood, metabolites (e.g., TCA) can persist in the blood for several weeks and in urine up to 3 weeks after heavy exposure (Monster et al., 1979; Sato et al., 1977). Immediate exposure is best measured by trichloroethanol levels in the blood. Chronic exposure is best measured by urinary TCA (Waksman & Phillips, 2004).

Caution. The presence of TCE metabolites should be interpreted with caution because some medications (chloral hydrate and disulfiram) and other chlorinated hydrocarbons (1,1,1-trichloroethane and tetrachloroethylene) are also metabolized to TCA and excreted in the urine (ATSDR, 2019).

The TCE metabolite, free trichloroethanol, can be measured in the blood. However, several other compounds affect the level of trichloroethanol found in the blood, thereby clouding the clinical significance of this metabolite as an indicator of TCE exposure. Thus, if higher-than-expected blood levels of trichloroethanol are detected, the clinician must consider alternate explanations for the elevated levels.

Conduct the following testing immediately to establish baseline values if acute exposure to TCE has resulted in marked CNS symptoms such as syncope:

• Liver function
• Blood urea nitrogen (BUN)
• Serum creatinine
• Urinalysis

Repeat testing if any of the results are abnormal, if the patient becomes symptomatic, or if there is any concern for ongoing exposure.

Liver function tests should include

• alkaline phosphatase
• alanine aminotransferase (ALT) (serum glutamic-pyruvic  transaminase SGPT)
• aspartate aminotransferase (AST) (serum glutamic-oxaloacetic transaminase SGOT)
• bilirubin
• lactate dehydrogenase

Transient elevations of serum levels of liver enzymes have been reported in TCE exposure, but hepatic necrosis is rare. If enzyme levels remain elevated, consider other causes of hepatic dysfunction and initiate appropriate clinical evaluation. Always consider alcohol consumption, infectious causes, nonalcoholic fatty liver disease, and other hepatotoxic xenobiotics in the differential diagnosis when interpreting abnormal liver function test results.

Neuropsychological testing might be useful for comparing exposed occupational populations to non-exposed control groups.

Contacting an expert in environmental and occupational medicine might provide information, assistance, and referral for clinical evaluation if the exposure history verifies environmental exposures.

Kidneys: Urinary excretion of glutathione-S-transferase alpha (Bruning et al., 1999), α1-microglobulin (Bolt, Lammert, Selinski, & Bruning, 2004), β2-microglobulin (Nagaya, Ishikawa, & Hata, 1989), and N-acetyl-β-D-glucosaminidase (Brogren, Christensen, & Rasmussen, 1986; Selden, Hultberg, Ulander, & Ahlborg, 1993) are used to indicate kidney damage, but none of these markers is specific to TCE-induced damage. A number of short-chain halogenated hydrocarbons can produce similar effects [ATSDR 2014]. Research studies have used these indicators to study kidney damage, but some of these are not readily available to clinicians, and the results are not specific to TCE-induced damage.

Heart: Electrocardiogram and continuous cardiac monitoring should be considered for heavily exposed persons.

Gastrointestinal: Ingestion of large amounts of TCE, which can cause nausea, vomiting, and diarrhea, can produce an electrolyte imbalance.

Nervous system: Because the trigeminal, optic, and facial nerves can be impaired by exposure to dichloroacetylene, changes in the visual fields and trigeminal nerve potentials can be noted (Szlatenyi & Wang, 1996).

Immune system: If autoimmune disease is suspected, consider expert consultation with a rheumatologist for appropriate serologic testing and other diagnostic workup.

• TCE exposure produces no unique clinical clues.
• Respiratory depression can result from acute, high-dose TCE exposure.
• At permissible workplace levels, CNS symptoms of TCE exposure, if any, are usually nonspecific and transient.
• TCE can be detected in blood, breath, and urine to confirm TCE exposure.
• Urinary proteins, liver function tests, a serum creatinine test, and continuous cardiac monitoring should be considered for persons acutely exposed to high levels of TCE.