Agency for Toxic Substances and Disease Registry
Case Studies in Environmental Medicine (CSEM) 

Tetrachloroethylene Toxicity
What Is the Biological Fate of Tetrachloroethylene in the Body?

Learning Objectives

Upon completion of this section, you will be able to

• explain the two major pathways of tetrachloroethylene metabolism in the body.

Introduction

In humans, about 75% of an inhaled tetrachloroethylene dose is absorbed by the lungs, and about 80% of an oral dose is absorbed by the gut. Tetrachloroethylene penetrates human skin slowly. Once tetrachloroethylene is absorbed, it is readily distributed to all body tissues. Because it is highly lipid soluble, it tends to concentrate primarily in adipose tissue.

Half-Life

More than 80% of inhaled tetrachloroethylene is eliminated unchanged by the lungs. The half-life of tetrachloroethylene in three major body compartments is calculated to be

• 12 - 16 hours for vessel-rich tissues,
• 30 - 40 hours for poorly perfused tissues such as muscle and
• 55 hours for adipose tissue

Metabolic Pathways

In humans, only 1% to 3% of the absorbed tetrachloroethylene is metabolized in the liver to trichloroacetic acid, which is then excreted in the urine. Small amounts of trichloroethanol have also been detected in the urine of workers exposed to tetrachloroethylene. The rate of urinary elimination is slower than the rate for exhalation.

Studies of dry-cleaning shop workers have shown that urinary metabolite levels increase linearly with air concentrations of up to 100 ppm tetrachloroethylene, then level off at higher concentrations. This indicates the saturability of the tetrachloroethylene metabolic pathways (Agency for Toxic Substances and Disease Registry 1997).

Metabolism of tetrachloroethylene occurs by cytochrome P450-dependent oxidation and glutathione conjugation. The cytochrome P450 pathway generates tri- and dichloroacetate as metabolites of tetrachloroethylene, and these are associated with hepatic toxicity and carcinogenicity. Glutathione conjugation pathway leads to selective formation of reactive metabolites in the kidneys. It is associated with tetrachloroethylene-induced renal toxicity and carcinogenicity (Lash and Parker 2001).

Key Points

• Once absorbed, tetrachloroethylene is eliminated unchanged in exhaled breath; a small amount is metabolized in the liver and excreted in urine as trichloroacetic acid and trichloroethanol.
• The elimination of tetrachloroethylene and its metabolites appears to be biphasic, with a rapid first phase (hours), and a slow second phase (days).

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