Trichlorethylene: Absorption, Elimination and Metabolism

Abstract

In a recent paper from this laboratory (Stewart and Witts, 1944) the clinical picture of chronic carbon tetra chloride intoxication was described. As a result of this experience it seemed desirable to devise quantitative methods for measurement of the degree of exposure to chloro-compounds of this type. Such methods would be of value not only in industrial medicine but also in therapeutics, as, for example, in studying the action and side effects of chloro-compounds used as anaesthetics and parasiticides. Subsequently a paper was published describing the estimation of trichlorethylene, chloroform and carbon tetrachloride in the blood in man (Habgood and Powell, 1945). The present paper, which is the third in the series, is a detailed study of the absorption and elimination of trichlorethylene. Trichlorethylene was chosen because we were able to study human sub jects to whom it was given as an anaesthetic. The results have nevertheless a wider application, since trichlorethylene (Truene, Westrosol, Crawshawpol) is used in industry in large quantities as a degreaser and a dry cleaning agent. Compared with tetrachlore thane and carbon tetrachloride, its toxicity is low (Hamilton, 1943) and some of the ill-effects which it is reported to produce in the nervous system can possibly be attributed to impurities, chiefly dichloracetylene, in the commercial preparation (Hunter, 1944). Although trichlorethylene was selected for study largely on the grounds of convenience and accessibility of cases, the results we have obtained have a special interest in view of the curious chemical reaction involved in the metabolism of trichlorethylene. Barrett and Johnston (1939) have found that 5-8 per cent, of the trichlorethylene absorbed by dogs during anaesthesia could be recovered from the urine as trichloracetic acid. The urine of human subjects who had been exposed to trichlorethylene vapour also gave chemical reactions indicative of the presence of trichloracetic acid, although the latter was not actually isolated (Barrett, Cunningham and Johnston, 1939). In the following investigation, trichlorethylene concentrations have been determined in blood during anaesthesia, and an attempt has been made to follow the elimination of trichlorethylene and its metabolite by analyses of blood, urine and expired air. We have been able to demonstrate that in man also trichlorethylene is in part metabolized to trichlor acetic acid. This phenomenon is of considerable chemical and toxicological interest. It is also probable that it could be applied as the basis of a simple urinary test for undue exposure to trichlorethylene in industry.