Abstract
Trichloroethylene (Tri) metabolites, i.e. chloral hydrate (Chl), trichloroethanol (TCE) and trichloroacetic acid (TCA), were administered to volunteers to determine the pharmacokinetic activity in the blood and urine. Immediate oxidation of Chl to TCA amounting to approx. 50% was followed by slow subsequent formation of TCA persisting for 30 h. TCA was also formed from TCE over a prolonged interval. After incorporation of Tri, Chl, or TCE, identical half-lives were found for TCE (approx. 12 h), while the TCA half-lives differed greatly, being most prolonged after Tri (approx. 100 h), somewhat lowered after Chl and TCE (approx. 65 h), and shortest after TCA (50 h). The reported findings indicate storage of both Tri and TCE in the tissues from which they are slowly released. As metabolite recovery invariably accounts for less than 50% of the doses ingested, it is suggested that additional pathways of elimination must be operative, chloroform constituting only a minor portion.
During industrial operations the degree of Tri inhalation varies considerably from one hour to the next and from day to day. Due to the completely different pharmacokinetic behavior of TCE and TCA, it is not permissible to evaluate previous exposure to Tri on the basis of the urinary TCE and/or TCA excretion.
Zusammenfassung
Die Metaboliten von Trichloräthylen (Tri), Chloralhydrat (Chl), Trichloräthanol (TCE) und Trichloressigsäure (TCA) werden an Probanden verabfolgt und ihre Pharmakokinetik in Blut und Harn verfolgt. Chl wird anfänglich sehr schnell zu TCA oxidiert (ca. 50%), danach folgt eine langsame, über 30 Std anhaltende Nachbildung. Auch aus TCE wird langanhaltend TCA gebildet. Nach Aufnahme von Tri, Chl oder TCE sind die Halbwertzeiten von TCE identisch (ca. 12 Std), die von TCA aber sehr verschieden: am längsten ist diese nach Tri (ca. 100 Std), geringer nach Chl und TCE (ca. 65 Std), am kürzesten nach TCA selbst (50 Std). Diese Befunde weisen auf eine Speicherung sowohl von Tri als auch von TCE im Gewebe mit langsamem Ausstrom. Stets werden weniger als 50% der aufgenommenen Dosen als Metaboliten wiedergefunden; es muß daher noch andere Eliminationswege geben, Chloroform nimmt nur einen unbedeutenden Anteil ein.
Tri wird in der Praxis in Mengen inhaliert, die von Stunde zu Stunde und von Tag zu Tag stark sehwanken. Da die Pharmakokinetik von TCE und TCA völlig unterschiedlich ist, ist es nicht gestattet, aus der Menge des im Harn ausgeschiedenen TCE und/oder TCA auf eine stattgehabte Tri-Exponierung zurückzurechnen.
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This study was supported by the Deutsche Forschungsgemeinschaft.
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Müller, G., Spassovski, M. & Henschler, D. Metabolism of trichloroethylene in man. Arch. Toxicol. 32, 283–295 (1974). https://doi.org/10.1007/BF00330110
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DOI: https://doi.org/10.1007/BF00330110