Introduction
Tetrachloromethane (carbon tetrachloride, CCl4) is a volatile, non-flammable chlorinated hydrocarbon that was once widely used as a solvent, dry-cleaning agent, grain fumigant and fire extinguisher component. Its use is now largely banned or strictly restricted, but poisoning still occurs through occupational exposure, accidental ingestion and misuse. This note covers the acute intoxication: sources and routes, mechanism, the staged clinical course, diagnosis, treatment, complications and prognosis.
Sources and routes of exposure
- Inhalation of vapour in poorly ventilated rooms, tanks or confined spaces (the main occupational route)
- Absorption through the skin after contact with the liquid
- Accidental or deliberate oral ingestion
- Heating near flames or hot metal produces toxic decomposition products such as phosgene, hydrogen chloride and chlorine, which add a separate airway injury
Mechanism of toxicity
The compound is lipophilic, so it is absorbed quickly and distributes into fatty tissue and the liver. Its toxicity depends on metabolic activation. In hepatocytes, cytochrome P450 2E1 converts it to the trichloromethyl radical, which in the presence of oxygen forms the trichloromethylperoxyl radical. These reactive species start lipid peroxidation of cell membranes, bind covalently to proteins and lipids, disturb calcium handling and damage mitochondria. Because CYP2E1 activity is highest in the centrilobular (zone 3) region of the liver lobule, necrosis is typically centrilobular. The kidney, with its proximal tubules, is injured by similar mechanisms.
Factors that increase toxicity include:
- Chronic alcohol use and enzyme inducers, which increase CYP2E1 activity
- Fasting or malnutrition, which lower glutathione stores and reduce detoxification
- Pre-existing liver or kidney disease