Section 2.1. Biological Fate of Tetrachloroethylene

Course: WB4066
CE Original Date: June 30, 2018
CE Expiration Date: June 30, 2020
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Learning Objectives

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

Overview

Tetrachloroethylene is rapidly and extensively absorbed after inhalation and oral exposure. Once absorbed, tetrachloroethylene is rapidly distributed throughout the body. The limited metabolism of tetrachloroethylene occurs through two pathways, oxidation via cytochrome P-450 and conjugation with glutathione. These pathways produce many metabolites, including some known to be cytotoxic, mutagenic, or both. The elimination of an absorbed dose of tetrachloroethylene occurs primarily in expired air as the parent compound.

Absorption and Distribution

The lungs absorb about 64%–100% of an inhaled dose of tetrachloroethylene [Chiu et al. 2007; Monster et al. 1979], and the gut absorbs almost 100% of an oral dose of tetrachloroethylene [Dallas et al. 1994a; Dallas et al. 1995)]. Only 1% is absorbed through contact with intact skin [Nakai et al. 1999; Wester et al. 2002].

After tetrachloroethylene is absorbed, it is readily distributed to all body tissues. Because it is highly lipid soluble, tetrachloroethylene tends to concentrate primarily in adipose tissue [Dallas et al. 1994a; Dallas et al. 1994b]. Tetrachloroethylene is also concentrated in breast milk [Schreiber 1997; Schreiber et al. 2002].

Metabolism and Toxicity

Tetrachloroethylene can be sequestered in fat because of its high lipid solubility; therefore, not all metabolism is evident in short sampling periods [EPA 2012a]. About 1%–3% of the estimated amount inhaled was metabolized to trichloroacetic acid (TCA) and other chlorinated oxidation products in a short period. Additional tetrachloroethylene (as much as 20% or more of the dose) may be metabolized over a longer period [Chiu et al. 2007; EPA 2012a; Monster et al. 1979]. These estimates appear to be consistent with the eliminated percentage of an oral or inhaled dose of tetrachloroethylene (see below).

Metabolism of tetrachloroethylene yields multiple toxic metabolites through two main pathways [Guyton et al. 2014; Lash and Parker 2001]:

  1. Oxidation via cytochrome P450—Metabolism via cytochrome P450 enzymes occurs predominantly in the liver. The pathway generates trichloroacetic acid (TCA) and dichloroacetic acid (DCA) as metabolites of tetrachloroethylene.
  2. Conjugation with glutathione—Tetrachloroethylene conjugation with glutathione (GSH) in the liver or kidney forms trichlorovinyl glutathione (TCVG), which is further processed in the kidney, forming the S-trichlorovinyl-L-cysteine (TCVC).

Studies have shown that these metabolites are cytotoxic, mutagenic, or both [Guyton et al. 2014; Lash and Parker 2001; NRC (National Research Council) 2010].

The parent compound tetrachloroethylene is also a likely contributing factor to neurotoxicity, particularly central nervous system (CNS) effects [Boyes et al. 2009; EPA 2012a].

Elimination

Mass-balance studies in rats with 14C-labeled tetrachloroethylene indicated that 70% or more of an oral or inhaled dose can be recovered in expired air as the parent compound. The next important excreted fraction in the form of trichloroacetic acid occurs in urine and feces, collectively accounting for up to 23% of an administered dose. A small portion of the dose (less than 3%) may be converted to CO2 and exhaled [Frantz 1983; NRC (National Research Council) 2010; Pegg et al. 1979].

The half-life of tetrachloroethylene in three major body compartments is calculated [Monster et al. 1979] to be

  • 12–16 hours for vessel-rich tissues such as brain, heart, lungs, kidneys, and liver;
  • 30–40 hours for poorly perfused tissues such as muscle; and
  • 55–65 hours for adipose tissue.
Key Point
  • Tetrachloroethylene rapidly absorbs into the bloodstream after oral and inhalation exposures.
  • 70% or more of an oral or inhaled dose can be recovered in expired air as the parent compound.
  • In general, metabolism of tetrachloroethylene yields multiple metabolites through two distinct pathways. These metabolites are associated with liver toxicity, renal toxicity, and carcinogenicity.
Page last reviewed: April 5, 2018