tion corrected for body mass in rats and humans. TCA excretion by rats was about 23 fold that of humans; or humans excreted about 4.4% of the amount excreted by rats.

The β-Lyase Pathway

Metabolism by the β-lyase pathway results in formation of dichloro protein adducts and DCA. Dichloro albumin adducts were detected in rat, but not human, blood samples after tetrachloroethylene exposure (Pahler et al. 1999). Even after immunoaffinity-column enrichment, the dichloro adduct was not detected in human samples. DCA is a stable product of the β-lyase pathway and is excreted in urine. Rats excreted DCA in urine at about one-tenth the amount of TCA, but DCA was not detected in urine collected from human volunteers after exposure to tetrachloroethylene (Volkel et al. 1998). That outcome is consistent with the lower activity of β-lyase in humans (McGoldrick et al. 2003).

The β-Lyase-Independent Pathway

Protein adducts resulting from the β-lyase-independent pathway have not been reported. N-Acetyl-TCVC, the mercapturate, is excreted in urine. Volkel et al. (1998) also measured urinary excretion of N-acetyl-TCVC after similar exposure to occupationally relevant concentrations of tetrachloroethylene. The Committee calculated the ratio of cumulative urinary excretion of N-acetyl-TCVC by rats to be about 5.5 fold that of humans; or humans excreted about 20% of the amount of N-acetyl-TCVC excreted by rats. Both rats and humans excrete much more TCA, the CYP-pathway product, than N-Ac-TCVC, but the ratio of N-acetyl-TCVC to TCA in humans is about 5 fold that of rats. That is, humans excrete relatively more tetrachloroethylene metabolites as N-Ac-TCVC than rats. That, too, is consistent with the lower activity of β-lyase in humans (McGoldrick et al. 2003); relatively more TCVC is metablized by the β-lyase-independent pathway in humans.

The National Academies of Sciences, Engineering, and Medicine
500 Fifth St. N.W. | Washington, D.C. 20001

Copyright © National Academy of Sciences. All rights reserved.
Terms of Use and Privacy Statement