Some science behind the scenes

Chloroform

Chloroform is an organic compound with formula CHCl₃. It is a colourless, sweet-smelling, dense liquid and is considered somewhat hazardous.

Chloroform has a multitude of natural sources – many marine in origin - brown, red and green seaweeds; the macroalga Eucheuma denticulatum; [which is cultivated and harvested on a large scale for carrageenan production]; Hypnea spinella; Falkenbergia hillebrandii; and Gracilara cornea along with seven indigenous macroalgae; brown and green algae; diatoms and others. It is also manufactured in considerable amounts. It is used for:

Making Teflon - Several million tons are produced annually as a precursor to Teflon and refrigerants, but its use for refrigerants is being phased out.

Solvent - Chloroform is a common solvent in the laboratory because it is relatively unreactive, miscible with most organic liquids, and conveniently volatile. It is also used as a solvent in the pharmaceutical industry and for producing dyes and pesticides. Chloroform is an effective solvent for alkaloids in their base form and thus plant material is commonly extracted with chloroform for pharmaceutical processing. For example, it is used in commerce to extract morphine from poppies and scopolamine from Datura plants.

Anaesthetic - Chloroform was once a widely-used anaesthetic. The Scottish obstetrician James Young Simpson first used chloroform for general anesthesia in 1847, for childbirth. The use of chloroform during surgery expanded rapidly thereafter in Europe. In the 1850s, chloroform was used during the birth of Queen Victoria's last two children. In the United States, chloroform began to replace ether as an anaesthetic at the beginning of the 20th century; however, it was quickly abandoned in favor of ether upon discovery of its toxicity, especially its tendency to cause fatal cardiac arrhythmia analogous to what is now termed "sudden sniffer's death".

Chloroform and toxicity

It has now been fairly well established that chloroform has a toxic action on the heart, liver and kidneys ‘although the exact nature and extent of these complications is still debated’ [Meyer]

There also seems to be some evidence that it isn’t terribly effective as an inducer of spiritual experience. I have included a number of examples the majority of which seem to indicate that very little happens except nausea, vomiting and headaches and if anything does it is more probably caused by hypoxia. Breathing about 900 ppm for a short time causes dizziness, fatigue, and headache and that is it.

It is also all too easy to give yourself a fatal dose of chloroform, with death due to respiratory or cardiac arrest. As might be expected for an anaesthetic, chloroform vapors depress the central nervous system. It is immediately dangerous to life and health at approximately 500 ppm, according to the U.S. National Institute for Occupational Safety and Health.

A great number of papers are available describing the damage done to the liver by chloroform exposure, for example:

Toxic damage of the liver by chloroform in chemical industry workers - [Article in German] - Bomski H, Sobolewska A, Strakowski A.

Hepatic function in workers exposed to inhalation of chloroform vapors - [Article in Italian] - Gambini G, Farina G. PMID: 4793806

and to the kidneys, for example:

The hands of John Snow: clue to his untimely death? - Mawson AR; .Department of Pediatrics, University of Mississippi Medical Center, Jackson, MS 39216 4505, USA.

The accomplishments of John Snow (1813-1858), physician-epidemiologist, inventor and anaesthetist to Queen Victoria, are well documented, but the causes of his untimely death at age 45 remain conjectural.

Snow suffered a paralysing stroke while working on his magnum opus, On Chloroform and Other Anaesthetics, and died a few days later on 16 June 1858.

Snow had a history of renal problems associated with tuberculosis. He also experimented on himself with ether, chloroform and other agents over several years, but whether this prolonged self-experimentation contributed to his early death is uncertain. A photograph of Snow taken in 1857 shows that the fingers of his right hand were swollen. Could this be a clue to the cause of his death?

The "modern" view is that Snow's early tuberculosis and associated renal disease led to hypertension, chronic renal failure and stroke. The tuberculosis and renal involvement may have been worsened by vegetarianism and perhaps resulting vitamin D deficiency. However, the renal damage caused by tuberculosis is unlikely to have been progressive.

Based on current evidence of renal toxicity associated with exposure to anaesthetic agents, it is perhaps more likely that extensive and prolonged self-experimentation with anaesthetics over a 9-year period led to Snow's renal failure, swollen fingers and early death from stroke.

Lethal complications after poisoning with chloroform--case report and literature review. Lionte C ; Medical Clinic, Sf.Ioan Emergency Clinic Hospital, Gr.T.Popa University of Medicine and Pharmacy, Iasi, Romania.

Chloroform is a potent central nervous system and respiratory depressant. The toxicities associated with chloroform frequently occur after inhalation. Hepatotoxicity is secondary to production of a toxic metabolite, with a peak elevation of liver enzymes 72 hours after exposure. Acute liver failure after chloroform inhalation is rarely described, this syndrome being produced mainly by viral hepatitis, idiosyncratic drug-induced liver injury, and acetaminophen ingestion. This report describes the case of a 46-year-old woman who presented to emergency department with coma, signs of respiratory failure, and solvent odor of her breath after chloroform inhalation and binge drinking. In evolution appeared lethal acute liver failure and rhabdomyolysis, despite maximum supportive care. Necroptic examination revealed microvesicular steatosis and tubular renal necrosis, specific for chloroform toxicity. This case illustrates the dramatic impact on liver of two well-recognized hepatotoxins. Mechanisms of chloroform and alcohol-induced liver toxicity are reviewed.

and some people develop sores and myeloma [cancer of plasma cells] when exposed to chloroform.

The relationship between multiple myeloma and occupational exposure to six chlorinated solvents.

Gold LS et al ; Program in Epidemiology, Fred Hutchinson Cancer Research Center, Seattle, Washington, USA.

OBJECTIVES:
Few studies have examined whether exposure to chlorinated solvents is associated with multiple myeloma. We evaluated associations between multiple myeloma and occupational exposure to six chlorinated solvents: 1,1,1-trichloroethane, trichloroethylene (TCE), methylene chloride (DCM), perchloroethylene, carbon tetrachloride and chloroform.

METHODS:
In-person interviews obtained occupational histories and information on jobs with likely solvent exposure. We assigned exposure metrics of probability, frequency, intensity and confidence using job-exposure matrices modified by job-specific questionnaire information. We used logistic regression to estimate ORs and 95% CIs for associations between multiple myeloma and ever exposure to each, and any, chlorinated solvent and analysed whether associations varied by duration and cumulative exposure. We also considered all occupations that were given the lowest confidence scores as unexposed and repeated all analyses.

RESULTS:
Risk of multiple myeloma was elevated for subjects ever exposed to 1,1,1-trichloroethane (OR (95% CI): 1.8 (1.1 to 2.9)). Ever exposure to TCE or DCM also entailed elevated, but not statistically significant, risks of multiple myeloma; these became statistically significant when occupations with low confidence scores were considered unexposed (TCE: 1.7 (1.0 to 2.7); DCM: 2.0 (1.2 to 3.2)). Increasing cumulative exposure to perchloroethylene was also associated with increasing multiple myeloma risk. We observed non-significantly increased multiple myeloma risks with exposure to chloroform; however, few subjects were exposed.

CONCLUSIONS:
Evidence from this relatively large case-control study suggests that exposures to certain chlorinated solvents may be associated with increased incidence of multiple myeloma; however, the study is limited by relatively low participation (52%) among controls.

Animal studies have shown that miscarriages occur in rats and mice that have breathed air containing 30 to 300 ppm of chloroform during pregnancy and also in rats that have ingested chloroform during pregnancy. Offspring of rats and mice that breathed chloroform during pregnancy have a higher incidence of birth defects, and abnormal sperm have been found in male mice that have breathed air containing 400 ppm chloroform for a few days. The effect of chloroform on reproduction in humans is unknown.

The US National Toxicology Program's eleventh report on carcinogens implicates it as reasonably anticipated to be a human carcinogen, a designation equivalent to International Agency for Research on Cancer class 2A. The IARC itself classifies chloroform as possibly carcinogenic to humans, a Group 2B designation. It has been most readily associated with hepatocellular carcinoma. Caution is mandated during its handling in order to minimize unnecessary exposure. ["International Agency for Research on Cancer (IARC) - Summaries & Evaluations: Chloroform". Retrieved 2010-09-02.]

Also "National Toxicology Program: Report on the carcinogenesis bioassay of chloroform".