CHAPTER 2-43: CARBON TETRACHLORIDE AND CHLOROFORM

INTRODUCTION

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).

MECHANISM OF TOXICITY

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.

TOXIC DOSE

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.

CLINICAL PRESENTATION

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.

DIAGNOSIS

Is based ...