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© 1984 Oxford University Press

research-article

Kinetics and Metabolism of Inhaled Methyl Chloroform (1,1,1-Trichloroethane) in Male Volunteers

RICHARD J. NOLAN1, NANCY L. FRESHOUR, DAVID L. RICK, LESLIE P. MCCARTY and JAMES H. SAUNDERS

H&ES, Toxicology Research Laboratory, The Dow Chemical Company 1803 Building, Midland, Michigan 48640

Kinetics and Metabolism of Inhaled Methyl Chloroform (1,1,1-Trichloroethane) in Male Volunteers. NOLAN, R. J., FRESHOUR, N. L., RICK, D. L., MCCARTY, L. P., AND SAUNDERS, J. H. (1984). Fundam, Appl. Toxicol. 4, 654–662. The kinetics of inhaled methyl chloroform (MQ and its principal metabolites, trichloroethanol (TCE) and trichloroacetic acid (TCA), were defined in six healthy male volunteers following single 6-hr exposures of 350 and 35 ppm. Blood and expired air MC concentrations were proportional to the exposure concentration and indicated that about 25% of the MC inhaled during the 6-hr exposure was absorbed. Elimination of MC was triexponential with half-lives estimated as 44 min, 5.7 hr, and 53 hr for the initial, intermediate, and terminal phases. Over 91% of the absorbed MC was excreted unchanged via the lungs, 5–6% was metabolized and excreted as TCE and TCA, and less than 1% remained in the body after 9 days. Urinary TCE and TCA excretion was extremely variable and indicated that urinary TCE and TCA measurements provide at best only a rough estimate of the exposure. These data suggest that the kinetics of MC in man are essentially first order at or below the current TL V of 350 ppm. Based on a comparison of the blood MC levels and amounts of MC metabolized, the rat is a better model than the mouse to predict the toxicity of MC in man.


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