Chloroform

CAS RN: 67-66-3

Health Effects

0.2.1 SUMMARY OF EXPOSURE
  • 0.2.1.1 ACUTE EXPOSURE
    • A) USES: Chloroform is a halogenated hydrocarbon. Historically, it had been used as an inhaled anesthetic; however, it is not currently used clinically for this indication due to cardiotoxic and hepatotoxic effects. Rarely, it is used recreationally as an inhalant. Currently, chloroform is used commonly in industrial processes as a precursor for chemical production, as a solvent, in chemical fire extinguishers, in analytical chemistry, in fumigants and insecticides, and in the rubber industry.
    • B) TOXICOLOGY: Chloroform toxicity occurs most commonly due to CNS depressant effects; as an inhaled anesthetic it causes inebriation, respiratory depression and hypoxia. The cardiotoxic effects due to chloroform are somewhat unclear in etiology, but are thought to be at least in part due to sensitization of the myocardium to catecholamines, leading to risk for developing dysrhythmias. The mechanism of chloroform-induced hepatic and renal toxicity is thought to be due to its toxic metabolites. The cytochrome system (unclear which isoenzymes) oxidizes chloroform to chloromethanol, which rapidly and spontaneously dechlorinates to create hydrochloric acid and phosgene. Phosgene in turn reacts with water to produce carbon dioxide and chloride ions and, with glutathione, to produce diglutathionyl dithiocarbonate. When glutathione is depleted to a critical level in the liver and kidney, excess phosgene covalently binds to tissue macromolecules, resulting in hepatic and renal necrosis.
    • C) EPIDEMIOLOGY: Poisoning is rare and most often occurs by the inhalational route, although intentional ingestions have been reported.
    • D) WITH POISONING/EXPOSURE
      • 1) MILD TO MODERATE TOXICITY: Common symptoms include nausea, vomiting, drowsiness, fatigue, headache, and nose and throat irritation.
      • 2) SEVERE TOXICITY: Common severe symptoms include CNS depression, myocardial depression, cardiac dysrhythmias, hypotension, respiratory depression, renal failure, hepatotoxicity, anoxia, and death. Dry mouth, hyperthermia, ataxia, chemical pneumonitis, dyspnea, delayed pulmonary edema, ARDS, hemolytic anemia, and leukocytosis may also be seen. Patients with chronic inhalational abuse may develop hallucinations, psychotic behavior, and white-matter degeneration.
      • 3) DERMAL EXPOSURE: Dermal contact results in irritation, reddening, burning pain, urticaria, vesiculation, and dermatitis via defatting.
      • 4) EYE EXPOSURE: Eye exposure to either the liquid or vapor forms of chloroform may cause conjunctivitis, blepharospasm, burning pain, and corneal epithelial injury.
0.2.3 VITAL SIGNS
  • 0.2.3.1 ACUTE EXPOSURE
    • A) WITH POISONING/EXPOSURE
      • 1) Hypotension and elevated temperature may be seen.
0.2.20 REPRODUCTIVE HAZARDS
  • A) Chloroform may be embryotoxic and induce changes in sperm morphology.
  • B) Chloroform has been listed by one reviewer as possibly teratogenic in humans (Hoffman, 1983), but the basis for this classification is not clear.
0.2.21 CARCINOGENICITY
  • 0.2.21.1 IARC CATEGORY
    • A) IARC Carcinogenicity Ratings for CAS67-66-3 (International Agency for Research on Cancer (IARC), 2016; International Agency for Research on Cancer, 2015; IARC Working Group on the Evaluation of Carcinogenic Risks to Humans, 2010; IARC Working Group on the Evaluation of Carcinogenic Risks to Humans, 2010a; IARC Working Group on the Evaluation of Carcinogenic Risks to Humans, 2008; IARC Working Group on the Evaluation of Carcinogenic Risks to Humans, 2007; IARC Working Group on the Evaluation of Carcinogenic Risks to Humans, 2006; IARC, 2004):
      • 1) IARC Classification
        • a) Listed as: Chloroform
        • b) Carcinogen Rating: 2B
      • 1) The agent (mixture) is possibly carcinogenic to humans. The exposure circumstance entails exposures that are possibly carcinogenic to humans. This category is used for agents, mixtures and exposure circumstances for which there is limited evidence of carcinogenicity in humans and less than sufficient evidence of carcinogenicity in experimental animals. It may also be used when there is inadequate evidence of carcinogenicity in humans but there is sufficient evidence of carcinogenicity in experimental animals. In some instances, an agent, mixture or exposure circumstance for which there is inadequate evidence of carcinogenicity in humans but limited evidence of carcinogenicity in experimental animals together with supporting evidence from other relevant data may be placed in this group.
  • 0.2.21.2 HUMAN OVERVIEW
    • A) Chloroform is listed as a suspected carcinogen.
  • 0.2.21.3 ANIMAL OVERVIEW
    • A) Chloroform is listed as a confirmed animal carcinogen with unknown relevance to humans
      • 1) (ACGIH, 2000)
    • A) .
0.2.22 GENOTOXICITY
  • A) Chloroform may be mutagenic and induce DNA damage, DNA repair, and sister chromatid exchanges.
  • B) Chloroform did not induce unscheduled DNA synthesis in vitro or in vivo in mice (Larson et al, 1994).
  • C) In one study, chloroform was mutagenic in E Coli WP2/pKM101 in the presence of glutathione-supplemented S9 mix. Chloroform was not mutagenic in Salmonella typhimurium TA98, TA100, TA1535, TA1537, or WP2uvrA/pKM101 with or without S9 mix, and was not mutagenic in TA98, TA100, TA1535, TA1537, or WP2uvrA/pKM101 in the presence of glutathione-supplemented S9 mix (Araki et al, 2004).
Find more information on this substance at: PubChem, PubMed