Agency for Toxic Substances and Disease Registry 
Case Studies in Environmental Medicine (CSEM) 

Tetrachloroethylene Toxicity
Clinical Assessment - Laboratory Tests

Learning Objectives

Upon completion of this section, you will be able to

• identify direct measurements that can assist with diagnosis of tetrachloroethylene exposure and
• identify indirect direct measurements that can assist with diagnosis of tetrachloroethylene exposure.

Introduction

Tetrachloroethylene may be measured to confirm tetrachloroethylene exposure. Significant exposure to tetrachloroethylene may result in elevated values of routine laboratory tests, including renal and liver function tests.

Direct Biologic Indicators

In exposed persons, tetrachloroethylene may be measured in

• adipose tissue,
• blood,
• breast milk,
• expired air, and
• urine

Its metabolite, trichloroacetic acid (TCA), may be measured in

• blood or
• urine

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.

If the cause of symptoms is questionable, direct biologic testing may be warranted to confirm tetrachloroethylene exposure.

Sample Collection

To measure tetrachloroethylene in blood or expired air, samples should be collected within 16 hours after exposure. Urine samples may remain positive up to five days after exposure, depending on the dose.

Few laboratories perform these specialized tests; regional poison control centers may be able to identify such facilities.

The method of sampling and sample storage must be coordinated with the laboratory to ensure proper specimen collection and processing.

The laboratory should provide reference values appropriate for the analytical method used, if they exist.

It is important to record the time of sample collection relative to the last exposure. Also note all possible sources of exposure, including the use of household products containing tetrachloroethylene and related chlorinated hydrocarbons.

Expired air and blood tetrachloroethylene levels and urine trichloroacetic acid levels have been linearly correlated with ambient air concentrations of up to 100 ppm (Agency for Toxic Substances and Disease Registry 1997).

In workers, a trichloroacetic acid level of 7 mg/L in urine, obtained at the end of the workweek, correlated with exposure to an average of 50 ppm tetrachloroethylene for 1 week. The same exposure level will result in approximately 100 μg/dL tetrachloroethylene in blood drawn 16 hours after the last work shift of the week (Agency for Toxic Substances and Disease Registry 1997).

Increased physical activity during exposure can result in higher levels (Agency for Toxic Substances and Disease Registry 1997).

It is important to note that the metabolism of tetrachloroethylene to trichloroacetic acid is inhibited by ethanol use; thus, a low trichloroacetic acid level cannot be used to assure safe exposure levels of tetrachloroethylene if the victim also uses alcohol (Reichert 1983).

Indirect Biologic Indicators

Although tetrachloroethylene may cause upper airway irritation and coughing, chest radiograph and 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 sought to study subclinical hepatotoxicity in dry cleaners exposed to tetrachloroethylene. It compared the sensitivity of hepatic parenchymal ultrasonography with measurements of serum transaminases as biomarkers of liver function (Brodkin, Daniell et al. 1995; Lash and Parker 2001). The study found mild to moderate changes in hepatic parenchyma more frequently in workers exposed to tetrachloroethylene than in a control population that was not exposed to any chemicals. In contrast, the incidence of increased serum alanine aminotransferase activity in these same workers was much less than that of the changes in ultrasonography.

However, when assessing hepatic parenchymal changes determined by nonspecific ultrasonography, the clinician must take into account synergism with other hepatotoxic factors when making the final clinical assessment of hepatoxicity from tetrachloroethylene. Such factors can include prescription medications, alcoholism, nutritional and/or genetic factors, and preexisting disease of the liver (Brodkin, Daniell et al. 1995; Brautbar and Williams 2002).

Baseline

If acute exposure to tetrachloroethylene has resulted in marked CNS symptoms such as syncope, then the following should be obtained immediately to establish baseline

• liver function tests
• blood urea nitrogen (BUN)
• serum creatinine
• urinalysis

Testing should be repeated after several days to monitor for possible effects.

Liver function tests should include

• alkaline phosphatase
• ALT (SGPT
• AST (SGOT)
• bilirubin
• lactic dehydrogenase

Transient elevations of serum levels of liver enzymes have been reported in tetrachloroethylene exposure, but frank hepatic necrosis has only rarely been documented.

If enzyme levels are mildly elevated, tests should be repeated in several weeks to document return to baseline. If levels remain elevated, consider other causes of hepatic dysfunction and initiate appropriate clinical evaluation.

Deciding when to obtain a neuropsychological evaluation in an individual patient for differentiating between organic and functional impairment may be challenging, especially when no baseline evaluation is available. Such tests may be most useful for comparing exposed occupational populations to nonexposed control groups. Neuropsychological tests may provide data that may be used to raise suspicion of cognitive impairments that are not otherwise evident on mental status testing, and they serve to define a clinical baseline for follow-up. Referral to a neurologist or occupational medicine specialist may be useful to determine whether neuropsychological testing is indicated in individual patients.

Key Points

• Tetrachloroethylene itself may be measured in breath, blood, urine, breast milk, and adipose tissue; its metabolites can be measured in blood and urine.
• Significant exposure to tetrachloroethylene may result in elevated values from renal and liver function tests.

Progress Check