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Metabolism of trichloroethylene in man

III. Interaction of trichloroethylene and ethanol

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Abstract

Volunteers inhaled a constant concentration of 50 ppm trichloroethylene (Tri) for 6 hrs per day on 5 consecutive days. Simultaneous ethanol (EtOH) ingestion (blood level 0.6 %.) inhibits the metabolization of Tri to triehloroethanol (TCE) and trichloroacetic acid (TCA) by 40 % on the average. Oxidation of Tri to TCA does not occur as long as EtOH is present. During this time period the blood Tri-concentration increases 21/2-fold, that in the expired air rising 4-fold, as compared to Tri inhalation without EtOH. TCE glucuronidation is not subject to inhibition. On concurrent inhalation of Tri, the EtOH and acetaldehyde levels are slightly increased over the control values without Tri.

The mechanisms underlying the alternate inhibition of mixed-function oxygenases and aldehyde dehydrogenase on simultaneous intake of Tri and EtOH are discussed. The intolerance reaction occurring on combined exposure to Tri and EtOH can be interpreted as an accumulation of Tri in the CNS resulting from the complete depression of Tri oxidation.

Zusammenfassung

Freiwillige Versuchspersonen inhalieren 6 Std pro Tag an 5 aufeinanderfolgenden Tagen eine gleichbleibende Konzentration von SOppm Trichloräthylen (Tri). Gleichzeitige Äthanol-(Ät-OH)-Einnahme (Blutspiegel 0,6 ‰) hemmt die Metabolisierung von Tri zu Trichloräthanol (TCE) und Trichloressigsäure (TCA) durchschnittlich um 40%. Solange ÄtOH gegenwärtig ist, findet keine Oxidation von Tri zu TCA statt. Während dieser Zeit erreicht Tri im Blut die 21/2fache, in der Ausatmungsluft die 4fache Konzentration, verglichen mit der Tri-Inhalation ohne ÄtOH. Die Glucuronidierung von TCE ist nicht meßbar eingeschränkt. Die ÄtOH- und Acetaldehydspiegel liegen bei gleichzeitiger TriInhalation geringfügig über den Kontrollwerten ohne Tri.

Die Mechanismen der wechselseitigen Hemmung von mischfunktionellen Oxygenasen und Aldehyddehydrogenase bei gleichzeitiger Aufnahme von Tri und ÄtOH werden diskutiert. Die Unverträglichkeitsreaktion, die bei kombinierter Exposition gegenüber Tri und ÄtOH auftritt, kann als Anstau von Tri im ZNS als Folge der vollkommen unterbundenen Tri-Oxidation gedeutet werden.

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Author notes

  1. M. Spassowski

    Present address: Institut für allgemeine Hygiene und Arbeitsschutz, Sofia, Bulgaria

Authors and Affiliations

  1. Institut für Pharmakologie und Toxikologie der Universität Würzhurg, Germany

    G. Müller, M. Spassowski & D. Henschler

Authors
  1. G. Müller
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  2. M. Spassowski
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  3. D. Henschler
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Additional information

This investigation was supported in part by the Deutsche Forschungsgemeinschaft.

We are grateful to Miss J. Ahamer and Mrs. R. Kraus for their skilled technical assistance.

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Müller, G., Spassowski, M. & Henschler, D. Metabolism of trichloroethylene in man. Arch Toxicol 33, 173–189 (1975). https://doi.org/10.1007/BF00311271

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  • DOI: https://doi.org/10.1007/BF00311271

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