CHAPTER 2-43: CARBON TETRACHLORIDE AND CHLOROFORM

Carbon tetrachloride (CCl4, tetrachloromethane) was once used widely as a dry cleaning solvent, degreaser, spot remover, fire extinguisher agent, and antihelminthic. Because of its liver toxicity and known carcinogenicity in animals, its role has become limited; it is now used mainly as an intermediate in chemical manufacturing.

Chloroform (trichloromethane) is a chlorinated hydrocarbon solvent used as a raw material in the production of freon and as an extractant and solvent in the chemical and pharmaceutical industries. Because of its hepatic toxicity, it is no longer used as a general anesthetic or antihelminthic agent. Chronic low-level exposure may occur in some municipal water supplies owing to chlorination of biologic methanes (trihalomethanes).

Carbon tetrachloride and chloroform are CNS depressants and potent hepatic and renal toxins. They may also increase the sensitivity of the myocardium to arrhythmogenic effects of catecholamines. The mechanism of hepatic and renal toxicity is thought to be a result of a toxic free radical intermediate (trichloromethyl radical) of cytochrome P450 metabolism. This radical can bind to cellular molecules (nucleic acid, protein, lipid) and form DNA adducts. Bioactivation of CCl4 has become a model for chemical toxicity induced by free radicals. The toxic reactions are important to elucidate the mechanisms of apoptosis, fibrosis, and carcinogenicity. Chronic use of metabolic enzyme inducers such as phenobarbital and ethanol increases the toxicity of carbon tetrachloride. Carbon tetrachloride is a known animal and a suspected human carcinogen. Chloroform is embryotoxic and is an animal carcinogen.

1. Toxicity from inhalation is dependent on the concentration in air and the duration of exposure.

   1. Carbon tetrachloride. Symptoms have occurred after exposure to 160 ppm for 30 minutes. The recommended workplace limit (ACGIH TLV-TWA) is 5 ppm as an 8-hour time-weighted average, and the air level considered immediately dangerous to life or health (IDLH) is 200 ppm.

   2. Chloroform. The air level considered immediately dangerous to life or health (IDLH) is 500 ppm. The recommended workplace limit (ACGIH TLV-TWA) is 10 ppm as an 8-hour time-weighted average.

2. Ingestion

   1. Carbon tetrachloride. Ingestion of as little as 5 mL has been reported to be fatal.

   2. Chloroform. The fatal oral dose may be as little as 10 mL, although survival after ingestion of more than 100 mL has been reported. The oral LD50 in rats is 2,000 mg/kg.

1. Persons exposed to carbon tetrachloride or chloroform from acute inhalation, skin absorption, or ingestion may present with nausea, vomiting, headache, dizziness, and confusion. Mucous membrane irritation is also seen with ingestion or inhalation. With serious intoxication, respiratory arrest, cardiac arrhythmias, and coma may occur.

2. Severe and sometimes fatal renal and hepatic damage may become apparent after 1–3 days.

3. Skin or eye contact results in irritation and a defatting type of dermatitis.

Is based on a history of exposure and the clinical presentation of mucous membrane irritation, CNS depression, arrhythmias, and hepatic necrosis. Carbon tetrachloride is radiopaque and may be visible on abdominal radiograph after acute ingestion.

1. Specific levels. Blood, urine, or breath concentrations may document exposure but are rarely available and are not useful for acute management. Qualitative urine screening for chlorinated hydrocarbons (Fujiwara test) may be positive after massive overdose.

2. Other useful laboratory studies include electrolytes, glucose, BUN, creatinine, liver aminotransferases, prothrombin time, and ECG monitoring.

1. Emergency and supportive measures

   1. Maintain an open airway and assist ventilation if necessary.

   2. Treat coma and arrhythmias (Table I–7) if they occur. Caution: Avoid the use of epinephrine or other sympathomimetic amines because they may induce or aggravate arrhythmias. Tachyarrhythmias caused by increased myocardial sensitivity may be treated with propranolol, 1–2 mg IV in adults, or esmolol, 0.025–0.1 mg/kg/min IV. Monitor patients for at least 4–6 hours after exposure and longer if they are symptomatic.

2. Specific treatment. N-acetylcysteine may minimize hepatic and renal toxicity by acting as a scavenger for the toxic intermediate. Acetylcysteine has been used without serious side effects for carbon tetrachloride or chloroform poisoning based on limited human reports. If possible, it should be given within the first 12 hours after exposure. Animal studies also suggest possible roles for cimetidine, calcium channel blockers, and hyperbaric oxygen in reducing hepatic injury, but there is insufficient human experience with these treatments.

3. Decontamination

   1. Inhalation. Remove from exposure and give supplemental oxygen, if available.

   2. Skin and eyes. Remove contaminated clothing and wash affected skin with copious soap and water. Irrigate exposed eyes with copious saline or water.

   3. Ingestion. Administer activated charcoal orally if conditions are appropriate (see Table I–38). Consider gastric lavage if the ingestion occurred within 60 minutes of presentation.

4. Enhanced elimination. There is no role for dialysis, hemoperfusion, or other enhanced removal procedures.