Introduction

Exposure to tetrachloroethylene can affect the

• central nervous system (CNS),
• eyes,
• kidney,
• liver,
• lungs,
• mucous membranes, and
• skin

CNS effects have been noted most frequently.

Acute Exposure

Acute exposure to tetrachloroethylene at air levels of 100 - 200 ppm causes irritation of the skin, eyes and upper respiratory tract (Boulet 1988). Non-cardiogenic pulmonary edema, nausea, vomiting, and diarrhea can occur (HSDB 2005) .

CNS effects have also been observed with acute inhalation exposures of 50 - 300 ppm of tetrachloroethylene. At these levels, neuromotor effects may be seen (e.g., the Romberg test may be positive), and results of certain coordination and behavioral tests may be abnormal. At higher concentrations in air, unconsciousness can occur.

Acute tetrachloroethylene ingestion has been reported. In one case, up to 16 g was ingested by a 6-year-old child, who recovered completely, without liver, renal, or CNS injury (Koppel, Arndt et al. 1985).

In another report, a 32-year-old man became semicomatose and experienced oliguric acute renal failure after accidental ingestion of 75 g of tetrachloroethylene. He regained normal renal function after five hemodialyses and conservative treatment (Choi, Kim et al. 2003).

Chronic Exposure

Chronic exposure to tetrachloroethylene may have adverse effects on the hepatic, renal, and nervous systems, and on the skin. It may increase the risk of adverse effects in fetuses and newborns through maternal exposure.

The U.S. Department of Health and Human Services (HHS) has determined that tetrachloroethylene is “reasonably anticipated to be a human carcinogen” (National Toxicology Program 2004). The International Agency for Research on Cancer (IARC) classified it as “probably carcinogenic to humans.”(International Agency for Research on Cancer (IARC) 1979; International Agency for Research on Cancer (IARC) 1987; International Agency for Research on Cancer (IARC) 1995) The classifications are based on sufficient evidence of tetrachloroethylene's carcinogenicity in animals, but inadequate evidence in humans.

Nervous System Effects

Acute exposures, depending on the concentration, can result in loss of coordination, reversible mood and behavioral changes, or potential anesthetic effects (Agency for Toxic Substances and Disease Registry 1997).

Persons chronically exposed to tetrachloroethylene may experience

• ataxia
• disorientation
• irritability
• peripheral neuropathy
• short-term memory deficits
• sleep disturbances

Studies of chronically exposed dry-cleaning workers have reported an increased prevalence of subjective neurological symptoms such as memory and concentration impairment, dizziness, and forgetfulness. Delayed reaction times also have been noted. In some patients, short-term memory impairments gradually cleared after exposure to tetrachloroethylene ceased. In such cases, patients may be mistakenly diagnosed with various forms of dementia, such as Alzheimer disease or other CNS disorders, when they in fact suffer from a preventable and possibly reversible toxic disorder (Seeber 1989).

Reversibility depends on the degree of severity of the exposure and associated effects.

Hepatic and Renal Effects

Case reports of human exposure to tetrachloroethylene show that it causes hepatotoxic effects in humans, which include

• abnormal liver function tests(Agency for Toxic Substances and Disease Registry 1997; Lash and Parker 2001) ,
• cirrhosis,
• hepatitis,
• hepatomegaly, and
• liver cell necrosis.

Most reported cases are due to accidental exposures or deliberate abuse of unknown dose and duration. Mild transient increases in serum transaminase values have occurred from brief but severe exposure in adults. Organ dysfunction has been noted only after months of exposure at tetrachloroethylene levels exceeding 100 ppm. There was one case report of diffuse fatty liver in a dry cleaner who died shortly after being exposed to tetrachloroethylene fumes (Levine, Fierro et al. 1981). In a mice study, hepatic lesions were observed at 37 ppm tetrachloroethylene and were noted to be most pronounced at exposures of 75 and 150 ppm (Kjellstrand, Holmquist et al. 1984).

Nephrotoxic effects have also been described in humans(Mutti, Alinovi et al. 1992; Verplanke, Leummens et al. 1999; Lash and Parker 2001). Hematuria and proteinuria have been associated with anesthetic concentrations of tetrachloroethylene, and chronically exposed dry-cleaning workers have been reported to have increased urinary levels of lysozymes, β2-microglobulin, and other low-molecular-weight proteins, suggesting tubular damage. Tetrachloroethylene exposure causes a toxic nephrosis in male rats, with characteristic nonproliferative tubular lesions that have also been noted after exposure to other chlorinated hydrocarbon solvents. Such specific renal effects have not been described in humans(Solet and Robins 1991) and may be species specific.

Cardiac Effects

In humans, high-level acute exposure to tetrachloroethylene can produce arrhythmias and pulmonary edema. It may produce a decrease in the myocardial threshold to the arrhythmogenic effects of epinephrine, which has been confirmed in rabbits but not in dogs. Another source has stated it is unlikely to cause such cardiac effects (HAZARDTEXT 2005; HSDB 2005).

Chronic exposure to tetrachloroethylene may cause ventricular arrhythmia or cardiomyopathy. An increased prevalence of heart disease was reported in one chronic exposure study, but cardiovascular problems were not more frequent in another (HAZARDTEXT 2005).

A case report described a dry cleaner who had symptomatic ventricular ectopy that was temporally correlated with work-related elevations of plasma tetrachloroethylene (Abedin, Cook et al. 1980).

Reproductive and Developmental Effects

The Camp LeJeune study (1998) reported an association between the effects of tetrachloroethylene-contaminated drinking water and small for gestational age (SGA) and mean birth weight difference (Sonnenfeld, Hertz-Picciotto et al. 2001). The New Jersey study (Bove, Fulcomer et al. 1995) found oral cleft defects associated with tetrachloroethylene-contaminated drinking water.

Tetrachloroethylene crosses the placenta and can be found in breast milk; therefore, the fetus and nursing newborn may be at increased risk of adverse effects from maternal exposure. The Nursing Mothers Study (Sheldon L 1985) identified PCE in blood, exhaled breath, personal air, and breast milk of 17 study participant.

Bagnell and Ellenberger (Bagnell and Ellenberger 1977) reported a case of obstructive jaundice and hepatomegaly in a 6-week-old breastfed infant exposed to PCE, who improved clinically after breast-feeding was discontinued; liver function was normal during two years of follow-up.

It is difficult to weigh the potential adverse effects of exposure to a contaminant via breast milk against the recognized benefits afforded by breast milk. Ideally, providing uncontaminated breast milk to an infant is the best choice. From a public health perspective, the avoidance of risk by minimizing exposure is sound public health policy. The risks associated with infant exposure to PCE are unnecessary risks since they can be reduced by avoiding exposure (Schreiber 1993).

Several studies have suggested that occupationally exposed women might suffer higher rates of spontaneous abortion and menstrual irregularities (Ahlborg 1990; Olsen, Hemminki et al. 1990; Doyle, Roman et al. 1997).

Results from inhalation studies in animals suggest that tetrachloroethylene is fetotoxic but not teratogenic at concentrations that are also maternally toxic (i.e., 300 ppm). Fetotoxicity is usually expressed by lower fetal weights and delayed skeletal ossification. In one animal study, (Fredriksson, Danielsson et al. 1993) gestational exposure resulted in behavioral and neurochemical alterations in some rats. Rats given oral doses of tetrachloroethylene for seven days became hyperactive, beginning at 10 days of age.

Carcinogenic Effects

The results of several studies suggest an association between tetra­chloro­ethylene exposure from drinking water and increased incidence of breast cancer, (Aschengrau, Paulu et al. 1998; Aschengrau, Rogers et al. 2003) lung cancer, (Paulu, Aschengrau et al. 1999) leukemia, (Cohn P 1994) non-Hodgkin's lymphoma, (Cohn P 1994) and other cancers, (Paulu, Aschengrau et al. 1999) although some uncertainties may exist in precision of the associations and exposure classification (Paulu, Aschengrau et al. 1999).

Some epidemiologic studies of dry-cleaning workers have suggested a possible association between chronic tetrachloroethylene exposure and increased cancer risk, including lymphoma and various cancers of the lung, esophagus, skin, cervix, uterus, liver, kidney, and bladder (Blair, Stewart et al. 1990; Lynge and Thygesen 1990). However, subjects in many of those studies had been simultaneously exposed to other solvents;(Brown and Kaplan 1987) most studies lacked information of exposure dose; and many studies failed to control for smoking, socioeconomic status, and other relevant risk factors (Green, Odum et al. 1990; Volkel, Friedewald et al. 1998; Mundt, Birk et al. 2003).

In studies using mice or rats, high-dose oral administration of tetrachloroethylene was associated with an increased incidence of hepatocellular carcinoma in mice of both sexes. Inhalation exposure was associated with leukemia in male and female rats, renal tubular cell adenomas and adenocarcinomas in male rats, and hepatocellular neoplasms in mice of both sexes (US Environmental Protection Agency. 1991). However, some studies indicated that tetrachloroethylene metabolism is significantly higher in rats than in humans, thus, using rat tumorigenicity data for human risk assessment of tetrachloroethylene exposure may overestimate human tumor risks (Green, Odum et al. 1990; Volkel, Friedewald et al. 1998).

Opinions vary on the predictive validity of mouse liver and kidney tumors in assessing carcinogenic risk in humans. In general, one should be careful in extrapolating evidence of liver and kidney tumors in experi­men­tal animals to human risk assessment (US Environmental Protection Agency 1991; Lash and Parker 2001). Significant increases in the understanding of how tetrachloroethylene and its metabolites act in the liver and kidney should help improve the precision of risk assessment.

Tetrachloroethylene has been clearly identified as a carcinogen in experimental animals (International Agency for Research on Cancer (IARC) 1979; US Environmental Protection Agency. 1985; National Toxicology Program (NTP) 1986; International Agency for Research on Cancer (IARC) 1987; US Environmental Protection Agency. 1991). The IARC (International Agency for Research on Cancer (IARC) 1979; International Agency for Research on Cancer (IARC) 1987; International Agency for Research on Cancer (IARC) 1995) considers it to be “probably carcinogenic to humans” and HHS believes it is “reasonably anticipated to be a human carcinogen” (National Toxicology Program 2004). These evaluations were based on the findings of limited evidence in humans and sufficient evidence in experimental animals of carcinogenicity.

Progress Check