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Metabolism, excretion and toxicology of methylchloroform in acute and subacute exposed rats

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Abstract

In acute and subacute inhalation studies rats were exposed to methylchloroform. In the 4-h exposure the concentrations were approximately 220 and 440 ppm, and in the 3-month study (5×8 h/week) approximately 204 ppm (MAC= 200 ppm).

The behavior of methylchloroform and its metabolites (trichloroethanol and trichloroacetic acid) in the expired air, blood, and urine was investigated. A gaschromatographic method for the determination of methylchloroform is described. Most of the methylchloroform is eliminated unchanged via the lungs.

In the subchronic inhalation studies, methylchloroform concentrations within the range of the MAC were tolerated with no symptoms. During this time, the concentrations of methylchloroform and trichloroethanol in the blood and the concentration of trichloroacetic acid in the urine remained constant. The urinary trichloroethanol excretion increased until the 10th week, then it fell and remained constant at a level somewhat below the maximum concentration. Methylchloroform was not detectable in organ tissue. The results of the metabolic studies are discussed.

Zusammenfassung

In akuten und subakuten Inhalationsversuchen wurden Ratten Methylchloroform exponiert. Bei den 4stündigen Expositionen waren die Konzentrationen ca. 220 und 440 ppm, im 3 Monateversuche (wöchentlich 5×8 Std) ca. 204 ppm (MAK-Wert: 200 ppm). Das Verhalten von Methylchloroform und seiner Metabolite (Trichloräthanol und Trichloressigsäure) in Atemluft, Blut und Harn wurde untersucht. Eine gaschromatographische Methode zur Methylchloroformbestimmung wird angegeben. Methylchloroform wird hauptsächlich unverändert abgeatmet. Als Metabolite wurden Trichloroäthanol und Trichloressigsäure nachgewiesen. In den subchronischen Inhalationsversuchen wurden von den Ratten Methylchloroformkonzentrationen im MAK-Bereich symptomlos toleriert.

Während dieser Zeit blieben die Konzentrationen von Methylchloroform und Trichloräthanol im Blut- und von Trichloressigsäure im Harn konstant. Die Trichloräthanolmenge im Harn stieg bis zur 10. Woche an und stellte sich dann auf einem Niveau etwas unterhalb der maximalen Konzentration ein. Im Organgewebe konnte Methylchloroform nicht nachgewiesen werden. Die Ergebnisse der Stoffwechseluntersuchungen werden diskutiert.

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We wish to express our thanks to Mrs. U. Gloy, Mrs. M. Gebauer, Mr. F. Tepper and Mr. U. Jansen for their technical assistance: Special thanks are given to Dr. G. Luckhaus for the histo-pathological investigations.

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Eben, A., Kimmerle, G. Metabolism, excretion and toxicology of methylchloroform in acute and subacute exposed rats. Arch. Toxicol. 31, 233–242 (1974). https://doi.org/10.1007/BF00311056

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