Metabolic interactions

• Carbon tetrachloride (CCl4)

Isopropanol may potentiate the hepatic and renal toxicity of carbon tetrachloride. Three workers in a colour printing factory were admitted to community hospitals with acute hepatitis, one worker also developed acute renal failure and pulmonary oedema. An investigation was carried out to determine the aetiology of the outbreak. Seventeen of twenty-five workers at the plant had abnormal liver function tests (LFTs) 10 days after the outbreak. It was found that there was a strong correlation between abnormal LFTs and the combined use of CCl4 and isopropanol in a cleaning process (Deng et al., 1987). A similar incident was reported by Folland et al. (1976). Fourteen of 43 workers developed non-specific illness when CCl4 was used to clean equipment close to an isopropanol packaging line. They developed symptoms of nausea, vomiting, headache, weakness and abdominal pain. Dizziness, blurred vision and diarrhoea were also reported. The illness lasted an average of 7 days. Two patients had signs of liver and renal toxicity. The onset and prevalence of illness was related to proximity to the area where the agents were being used. The potentiating interaction in these cases may also be related to the presence of acetone, the main metabolite of isopropanol. Acetone is known to induce the CYP2E1 enzyme (Morgott, 2001), and induction of this pathway contributes to the increased toxicity in a combined CCl4/isopropanol exposure.

Many alcohols are metabolised by liver alcohol dehydrogenase (ADH). As ADH has a much higher affinity for its preferred substrate, ethanol, the metabolism of many other alcohols can be reduced or even completely blocked by the concurrent administration of, or exposure to, ethanol. The metabolism of isopropanol may be blocked in this way (Alexander et al., 1982). The significance of this interaction for the occupational setting is unclear, but as there has been some suggestion that isopropanol is twice as potent a CNS depressant as ethanol (Lacouture et al., 1983; Smith, 1983), concurrent exposure to these agents may prolong the depressant effects of isopropanol.

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