Biological Fate of Trichloroethylene

After completing this section, you will be able to explain the major pathways of TCE metabolism in the body.

TCE is readily absorbed into the bloodstream, regardless of the route of exposure, and rapidly distributed throughout the body via the circulatory system. Metabolism of TCE in the kidneys and liver plays a key role in TCE toxicity. The majority of TCE absorbed into the body is eliminated by metabolism.

TCE is a lipophilic, volatile compound that is readily absorbed from inhaled air. Uptake from inhalation is rapid. The absorbed dose is proportional to the exposure concentration and duration and pulmonary ventilation rate. Available reports on human exposure to TCE via ingestion are largely restricted to case reports of occupational or intentional (suicidal) ingestions and suggest significant gastric absorption. Absorption through the skin has been shown to be rapid after vapor and liquid TCE contact with the skin (EPA, 2011c).

Several studies of tissue distribution in humans after inhalation exposure to TCE reported that the relative proportions varied among individuals, but the major sites of distribution appeared to be body fat and the liver. (ATSDR, 2019).

TCE undergoes metabolism by two distinct pathways:

• CYP-oxidation by a cytochrome P450 enzyme
• GSH-conjugation by the compound glutathione

These two metabolic pathways usually modify substances that enter the body to make them less toxic and more likely to be eliminated by excretion. However, in some cases (as with TCE), the chemical modifications can instead make the substance more toxic (NTP, 2016).

The mutagenic and carcinogenic potential of TCE is generally thought to result from reactive intermediate biotransformation products rather than TCE itself.

The CYP-oxidation-derived metabolites of TCE that have been associated with specific target organs, such as the liver and lungs, include the following:

• chloral hydrate
• trichloroacetic acid (TCA)
• dichloroacetic acid

The GSH-conjugation-derived metabolites of TCE that have been associated with the kidney as a target organ include the following:

• dichlorovinyl glutathione
• dichlorovinyl cysteine (DCVC)

The majority of TCE absorbed into the body is eliminated by metabolism. Kidney cancer most likely occurs as a result of GSH conjugation of TCE, whereas liver cancer most likely occurs as a result of the CYP-oxidation pathway (Chiu et al., 2013; EPA, 2011c; NTP, 2016; Rusyn et al., 2014).

Although a small amount of absorbed TCE is exhaled unchanged, most of an absorbed dose is metabolized in the body. With the exception of carbon dioxide, which is eliminated solely via exhalation, most TCE metabolites have low volatility and, therefore, are excreted primarily in urine and feces (EPA, 2011c).

The time between TCE inhalation and urinary excretion of trichloroethanol is relatively short (biologic half-life = approximately 10 hours) compared with the urinary excretion of trichloroacetic acid (biologic half-life = approximately 52 hours). Trichloroacetic acid is theoretically detectable in urine for at least a week after TCE exposure (Monster, Boersma, & Duba, 1979; Sato, Nakajima, Fujiwara, & Murayama, 1977).

• TCE is readily absorbed into the bloodstream regardless of the route of exposure.
• The majority of TCE absorbed into the body is eliminated after metabolism through the urine and feces.
• The mutagenic and carcinogenic potential of TCE is the result of TCE metabolites rather than TCE itself.

To review relevant content, see all contents in Section 2.1.