Trichloroethylene is a colorless liquid which is widely used in industry as a metal degreaser and as a solvent (solvent for cleaning metal parts).
TCE is one of the most common chemicals found at Superfund sites and as such is often a chemical of concern when a cancer cluster is reported. Most human exposure to TCE is airborne, but TCE can also persist in groundwater. Yet, the regulation of TCE in the mentioned media is continuously evolving with high uncertainty outcome. EPA has not had definitive guidance or policy regarding TCE toxicity for a number of years. Different toxicity values ranging over approx. two orders of magnitude are currently in use by regulatory bodies at federal and state level. Until a final decision followed by an MCL and air limit is taken, the best we can do is try to minimize any potential risk by targeting a TCE concentration as close to zero as possible.
The most serious health effect of TCE is its carcinogenic effect (capacity to induce cancer in humans). The current state of knowledge related to TCE health effects show the clear potential to induce cancer in humans and it does not allow us to establish a certain TCE dose above which the cancer risks will be eliminated. Until our knowledge will permit the acknowledgment of such dose, all we can do to protect human health is to consider that the presence of TCE may be harmful in any amount and our goal should be the same with EPA MCLG for TCE - which means zero.
The scientific information about the health effects of TCE comes mainly from animal studies and from people exposed to high levels in the course of their work. The epidemiologic research on TCE has been complicated by the lack of quantitative exposure information and the presence of other chemical exposures among workers studied.
Short-term exposure to high levels of TCE - People may experience headaches, drowsiness and eye, nose, or skin irritation from exposure to high levels of TCE. At very high levels, people can lose consciousness. Behavior changes have been observed in animals after exposure to high levels of TCE.
Long-term exposure to high levels of TCE in drinking water can damage the liver, kidney, immune system, and the nervous system. TCE may also harm a developing fetus if the mother consumes water containing high levels of TCE. Also, occupational exposure to TCE at higher levels may be associated with elevated risk for non-Hoggkin’s lymphoma (Raaschou-Nielsen et al., 2003). Occupational exposure was also associated with an increased risk of systemic sclerosis (Pumford, 2004) and in general with autoimmune diseases.
Long-term exposure to low levels of TCE, mainly by drinking water, may be associated with neurobehavioral deficits (Reif et al., 2003) or congenital heart disease (Goldberg et al., 1992; Johnson et al., 2003). An article by Kilburn (2002) is mentioning about the health effects recorded for workers exposed to a low TCE dose daily, stating that lassitude, headache, irritability, and mental confusion were accompanied by delayed blink latency and physiological deterioration in two groups: workers and volunteers. Some studies (Lee et al., 2003) suggest that exposure to low levels of TCE over many years may also be linked to an increased risk of several types of cancer. It is likely that the adverse health effects that can result from exposure to TCE come not from the TCE itself, but from other compounds that are produced when the body breaks down TCE.
Although a chronic-duration inhalation health comparison value (MRL, or minimal risk level) is currently not available, ATSDR has derived an intermediate-duration MRL of 537 g/m3 (100 ppb) for inhalation exposure to TCE. The MRL is based on neurological effects on rats observed in a 1994 study. An EPA inhalation reference concentration (RfC) of 40 g/m3 has also been derived, and is based on critical effects in the central nervous system, liver, and endocrine system.
TCE is an animal carcinogen with limited evidence of carcinogenicity in humans. There are multiple carcinogenic metabolites acting through multiple modes of action. Related to the mechanism inducing cancer in humans, a presentation by Bull (2004) concluded that the mixed phenotype of tumors induced by TCE indicates that both DCA and TCA contribute. DCA contribution is likely to be a combined action between inhibition of TCA-dependent phenotype and stimulation/creation of DCA-dependent phenotype. The carcinogenic mechanisms of TCE is also presented in detail by Lash (2004) and by Pereira (2004), who concluded that the mechanism of DCA and TCA (TCE metabolites) carcinogenic activity could be explained by their ability to induce DNA hypomethylation and thus increase the risk of cancer, while also hypermethylation of tumor suppressor genes is involved in DCA and TCA carcinogenic activity.
In 1985, EPA classified TCE as a probable human carcinogen. Three years later, EPA reviewed information suggesting the weight-of-evidence was on a possible human carcinogen - probable human carcinogen continuum. Under EPA's proposed (1996, 1999) cancer guidelines, TCE can be characterized as "highly likely to produce cancer in humans." These findings are consistent with those of the International Agency for Research on Cancer and the National Toxicology Program. As a result of the reassessment, EPA withdrew the inhalation and oral unit risk values. In experimental rodent studies, high doses of TCE administered to mice resulted in tumors of the lungs, liver, and testes. Other possible cancers associated with exposure to high levels of TCE include cancer of the bladder, stomach, prostate, kidney, and pulmonary system.
(http://www.atsdr.cdc.gov/HAC/PHA/palermo/pwf_p1.html#disc) . So far, no clear dose-response relationship appeared for any of the cancers associated with TCE exposure (Hansen et al., 2001).
In 1996, TCE was also classified as belonging to the German MAK group III A1, meaning carcinogenic to humans based on effects on the tubular system of the human kidney.
TCE is an example of a chemical for which the regulation is complex and continuously changing with an uncertain final outcome. TCE should remind us of the many limitations of modern toxicology when judging the risks mainly based on animal studies. Below are key aspects related to the development, the present and the future of TCE regulation.
The current TCE limits are: for water MCL: 0.005 mg/L, MCLG: zero; for air: the old withdrawn value (EPA 1989) is of 1.43 ug/m3, the more conservative “new provisional value” (EPA 2001) for indoor air (assuming a cancer risk of 10-6) is 0.021 ug/m3, while the less conservative “new provisional value” is much higher (0.43 ug/m3); the Cal EPA Air Toxics Hot Spots Program (2002) recommends a different TCE air value of 1.2 ug/m3, and Colorado Department of Public Health and Environment (CDPHE) is using a value of 0.016 ug/m3.