Section 2.2. Clinical Effects

After completing this section, you will be able to describe the clinical effects associated with tetrachloroethylene exposure.

The central nervous system, liver, kidney, and reproductive system are target organs of tetrachloroethylene toxicity [EPA 2012b].

Tetrachloroethylene hepatic effects are thought to result from oxidative metabolites [Buben and O’Flaherty 1985], whereas metabolites resulting from glutathione conjugation are thought to cause kidney effects [Lash and Parker 2001]. Tetrachloroethylene itself has been presumed to cause neurological effects [Guyton et al. 2014].

Epidemiologic studies have shown associations between tetrachloroethylene exposure and several types of cancer.

Neurotoxicity is a sensitive outcome seen in humans and experimental animals exposed to tetrachloroethylene by inhalation or ingestion. A wide range of effects on neurologic function have been observed in humans after acute and chronic exposure to tetrachloroethylene. Vision and cognitive function are most commonly affected [EPA 2012a; Guyton et al. 2014; Schreiber et al. 2002].

Symptoms temporally related to exposure are a function of the anesthetic property of organic solvents. Specifically, dizziness, light-headedness, impaired concentration, and headaches that have a temporal relationship to solvent exposure are likely the result of the acute CNS effects [Meredith et al. 1989; Rom 2007]. These symptoms are likely to resolve quickly after moving from the contaminated environment to fresh air and might significantly improve or resolve by the time a healthcare professional evaluates the patient.

Hepatotoxic effects such as hepatomegaly, hepatocellular damage, and elevations of gamma-glutamyltransferase and bilirubin degradation byproducts have been observed after acute high-level exposure to tetrachloroethylene [ATSDR 2015; EPA 2012a; Lash and Parker 2001].

Some cross-sectional studies of occupationally exposed dry cleaning workers [Brodkin et al. 1995; Gennari et al. 1992] showed indications of liver toxicity. Mild to moderate hepatic parenchymal changes occur more frequently in workers exposed to tetrachloroethylene than in populations not exposed to chemical solvents.

Studies have also reported liver toxicity in multiple animal species as a result of inhalation and oral exposures to tetrachloroethylene [ATSDR 2015; EPA 2012a; Lash and Parker 2001].

Several studies have described nephrotoxic effects in humans [ATSDR 2015, 2017; EPA 2012a; Lash and Parker 2001; Mutti et al. 1992; Verplanke et al. 1999]. Hematuria and proteinuria have been associated with anesthetic concentrations of tetrachloroethylene. Chronically exposed dry-cleaning workers have increased urinary levels of lysozymes, β2-microglobulin, and other low-molecular-weight proteins, suggesting tubular damage.

Adverse effects on the kidneys have been observed in studies of animals exposed to high concentrations of tetrachloroethylene by inhalation, oral gavage, and intraperitoneal injection of tetrachloroethylene metabolites [ATSDR 2015; EPA 2012a; Lash and Parker 2001].

A number of studies of tetrachloroethylene exposure have evaluated reproductive outcomes, including

• menstrual disorders,
• altered semen quality,
• reduced fertility,
• increased time to pregnancy, and
• adverse pregnancy outcomes (such as spontaneous abortion, low birth weight or gestational age, and stillbirth).

However, the evidence is inconclusive [ATSDR 2015; EPA 2012a].

Studies of tetrachloroethylene in drinking water have reported that exposure during pregnancy is associated with low birth weight and oral clefts [Aschengrau et al. 2009; Bove et al. 1995; Sonnenfeld et al. 2001]. However, due to several limitations of these studies, firm conclusions cannot be drawn [EPA 2012a].

Tetrachloroethylene crosses the placenta and can be found in breast milk; therefore, the fetus and nursing newborn might be at increased risk for adverse effects from maternal exposure [Bagnell and Ellenberger 1977; Schreiber 1993; Sheldon L and Zelon H 1985].

Evidence from a limited number of well-conducted reproductive studies in laboratory animals suggests that tetrachloroethylene is a potential female reproductive toxicant, resulting in decreased number of liveborn pups, increased pre-and post-implantation loss, and increased resorptions [ATSDR 2015].

The available epidemiologic studies provide a pattern of evidence associating tetrachloroethylene exposure and several types of cancer, specifically bladder cancer [Aschengrau et al. 1993; Blair et al. 2003; Lynge et al. 2006; Pesch et al. 2000], non-Hodgkin’s lymphoma [Anttila et al. 1995; Radican et al. 2008; Seldén 2011], and multiple myeloma [Gold L et al. 2010; Radican et al. 2008].

In a recent report, ATSDR concludes that information is insufficient to determine whether a causal association exists for tetrachloroethylene and multiple myeloma [ATSDR 2017].

Other epidemiologic studies suggest possible associations with other cancer sites (bone marrow, esophageal, kidney, lung, liver, cervical, and breast cancer), but the data are more limited or inconsistent [ATSDR 2015, 2017; EPA 2012a].

The administration of PCE, either by ingestion or by inhalation to sexually mature rats and mice, increases tumor incidence (such as mononuclear cell leukemia, kidney, or hepatocellular tumors) [Japan Industrial Safety Association (JISA) 1993; National Cancer Institute 1977; National Toxicology Program (NTP) 1986].

The International Agency for Research on Cancer (IARC) classified tetrachloroethylene as a Group 2A agent— “probably carcinogenic to humans” [IARC 1995], The U.S. Department of Health and Human Services believes it is “reasonably anticipated to be a human carcinogen” [NTP 2014]. The U.S. Environmental Protection Agency (EPA) characterizes tetrachloroethylene as “likely to be carcinogenic to humans” [EPA 2012a]. These evaluations are based on the findings of limited evidence in humans and sufficient evidence of carcinogenicity in experimental animals.

The available studies of immunological effects in humans exposed to tetrachloroethylene provide suggestive evidence for alterations in blood biomarkers (e.g., IgE and cytokine levels) related to inflammation and hypersensitivity. However, the data are limited and exposure concentrations are uncertain. Evidence suggests subtle perturbations of the immune system in animals exposed to tetrachloroethylene, but the data are limited and the relevance to humans is uncertain at present; further research is needed [ATSDR 2015].

Chemical burns characterized by severe cutaneous erythema, blistering, and sloughing have resulted from prolonged (more than 5 hours) accidental contact exposure to tetrachloroethylene used in dry-cleaning operations [ATSDR 2015].

• Neurotoxicity is a sensitive outcome of either oral or inhalational exposure to tetrachloroethylene in humans and experimental animals.
• Tetrachloroethylene may also adversely affect the liver and kidneys.
• Studies suggest tetrachloroethylene exposure may cause adverse reproductive outcomes. It might harm the fetus and newborn through maternal exposure.
• IARC has classified tetrachloroethylene as “probably carcinogenic to humans” (Group 2A).