Section 3.1. Evaluation and Diagnosis

After completing this section, you will be able to

• describe what is included in the initial history of patients potentially exposed to tetrachloroethylene,
• describe what is included in the physical examination of patients potentially exposed to tetrachloroethylene,
• describe possible clinical symptoms in patients exposed to tetrachloroethylene, and
• identify tests that can help diagnose tetrachloroethylene toxicity.

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

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

• determine possible sources and pathways of exposure to tetrachloroethylene,
• detect symptoms and signs attributable to tetrachloroethylene 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. Taking an exposure history may 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 tetrachloroethylene 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 tetrachloroethylene 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

The patient’s occupational history is crucial. For each job held, the exposure history should include

• Company name and location
• Job title (previous work and type of occupation)
• Description of chemical processes used
• Known toxic agents
• History of worker illness
• Enclosure of solvent-related processes
• Use of a hood or other ventilation
• Use of personal protective equipment (such as respirator and gloves)

Collect information on the specific constituents of the solvent-containing materials and other potentially hazardous substances used. You might need to ask employers, suppliers, or manufacturers for the safety data sheet (SDS) (formerly known as material safety data sheet [MSDS]). Determine the patient’s use of personal protective equipment. The occupational history should also include the patient’s general assessment of the hygienic conditions of the work setting, including the availability of separate washing, changing, and eating facilities. Also ask the patient about potential exposure(s) from the activities of coworkers.

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.

*ATSDR has developed other CSEMs, including “Taking an Exposure History” and “Taking a Pediatric Exposure History.” To view these CSEMs, please go to https://www.atsdr.cdc.gov/csem/.

When performing the physical examination, focus on the major organ systems that tetrachloroethylene exposure is likely to affect (e.g., CNS, hepatic, renal, reproductive, and skin) [Rom 2007]. 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, especially the hands, for signs of

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

Also note signs of hepatic dysfunction (e.g., jaundice).

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 peripheral nerve function by evaluating

• proprioception,
• deep tendon reflexes,
• motor strength,
• 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. CNS symptoms can be similar to those of ethanol inebriation.

Patients with some of the following symptoms, grouped by system, might have acute high-level tetrachloroethylene exposure:

Nervous system

• Confusion
• Dizziness
• Euphoria
• Forgetfulness
• Headache
• Irritability
• Light-headedness
• Loss of consciousness
• Loss of coordination
• Sleepiness
• Slurred speech

Gastrointestinal

• Nausea

Ear, nose, and throat

• Cough
• Eye and nose irritation
• Upper airway irritation

Mild CNS symptoms have reportedly resulted from exposure to tetrachloroethylene-containing household products in confined spaces and after exposure in industrial settings. Reported symptoms from chronic inhalation exposure have included

• ataxia,
• disorientation,
• irritability,
• persistent headache,
• short-term memory deficits, and
• sleep disturbances.

The liver is the primary target organ in animals exposed chronically to tetrachloroethylene. In humans, chronic exposure has led to hepatitis and elevated transaminase levels. You may also note signs of hepatic dysfunction (e.g., jaundice).

Tetrachloroethylene’s defatting action on skin may cause dermatitis, thereby predisposing the skin to infection.

Tetrachloroethylene may be measured to confirm tetrachloroethylene exposure. Significant exposure to tetrachloroethylene can result in elevated values of routine laboratory tests, including renal and liver function tests, although they are not specific to tetrachloroethylene exposure.

For acute exposures, tetrachloroethylene in expired air can be measured although it might also be detected in blood or urine [Baselt 1997; Imbriani et al, 1988]. Although tetrachloroethylene can be measured in breath, blood or urine, these laboratory studies are not rapidly available and do not change management priorities. Thus the diagnosis of hydrocarbon exposure is based upon clinical features [Lewander WJ and Aleguas, A. 2017].

For chronic exposures, urine or blood levels of trichloroacetic acid (TCA) can be measured. However, exposure to other chemicals, such as 1,1,1-trichloroethane and trichloroethylene, also produce trichloroacetic acid in blood and urine, as does use of the prescription sedative chloral hydrate. Thus, the presence of this particular metabolite is not specific to tetrachloroethylene exposure.

In a random sampling of 2,735 participants in the 2007–2008 U.S. National Health and Nutrition Examination Survey (NHANES), blood concentrations of tetrachloroethylene ranged from below the limit of detection up to 0.094 ng/m [CDC 2017].

Although tetrachloroethylene can cause upper airway irritation and coughing, chest radiograph and pulmonary function tests are usually normal.

In general, results of routine laboratory tests, including renal and liver function tests, will also be normal, unless the patient has had an exposure significant enough to cause concurrent neurological symptoms.

One study looked at subclinical hepatotoxicity in workers exposed to tetrachloroethylene in dry cleaning establishments. It compared the sensitivity of hepatic parenchymal ultrasonography with measurements of serum transaminases as liver biomarkers [Brodkin et al. 1995; Lash and Parker 2001]. The study found mild to moderate changes in hepatic parenchyma (i.e., diffuse parenchymal changes in echogenicity) more frequently in workers exposed to tetrachloroethylene than in a control population not exposed to tetrachloroethylene. In contrast, the incidence of increased serum alanine aminotransferase activity in these same workers was much less than that of the changes in ultrasonography.

When assessing hepatic parenchymal changes determined by ultrasonography, the clinicians should also take into account of other hepatotoxic factors when making the final clinical assessment of hepatotoxicity from tetrachloroethylene. Such factors can include prescription medications, alcoholism, nutrition, genetics, and preexisting disease of the liver [Brautbar and Williams 2002; Brodkin et al. 1995].

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

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

Repeat testing after several days to monitor for possible effects.

Liver function tests should include

• alkaline phosphatase,
• ALT (SGPT),
• AST (SGOT),
• bilirubin, and
• lactate dehydrogenase.

Transient elevations of serum levels of liver enzymes have been reported in tetrachloroethylene exposure, but documented hepatic necrosis is rare.

If enzyme levels remain elevated, consider other causes of hepatic dysfunction and initiate appropriate clinical evaluation. Always consider alcohol consumption when interpreting liver function test results.

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

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

• An exposure history should be part of the patient history.
• Establishing a temporal relationship between the patient’s signs and symptoms and exposure to tetrachloroethylene can aid in diagnosis.
• Patients exposed to tetrachloroethylene by any route predominantly exhibit CNS symptoms.
• Although testing may measure tetrachloroethylene in breath, blood, urine, breast milk, and adipose tissue, etc., this testing is mainly useful in research and not in routine clinical evaluation.