Chloroform, or trichloromethane, is an
organic compound
In chemistry, organic compounds are generally any chemical compounds that contain carbon-hydrogen or carbon-carbon bonds. Due to carbon's ability to catenate (form chains with other carbon atoms), millions of organic compounds are known. T ...
with
formula C H Cl3 and a common organic
solvent
A solvent (s) (from the Latin '' solvō'', "loosen, untie, solve") is a substance that dissolves a solute, resulting in a solution. A solvent is usually a liquid but can also be a solid, a gas, or a supercritical fluid. Water is a solvent for ...
. It is a colorless, strong-smelling, dense liquid produced on a large scale as a precursor to
PTFE. It is also a precursor to various
refrigerants.
It is
trihalomethane
In chemistry, trihalomethanes (THMs) are chemical compounds in which three of the four hydrogen atoms of methane () are replaced by halogen atoms. Many trihalomethanes find uses in industry as solvents or refrigerants. THMs are also environmenta ...
. It is a powerful
anesthetic
An anesthetic (American English) or anaesthetic (British English; see spelling differences) is a drug used to induce anesthesia — in other words, to result in a temporary loss of sensation or awareness. They may be divided into two ...
,
euphoriant
Euphoria ( ) is the experience (or affect) of pleasure or excitement and intense feelings of well-being and happiness. Certain natural rewards and social activities, such as aerobic exercise, laughter, listening to or making music and danci ...
,
anxiolytic
An anxiolytic (; also antipanic or antianxiety agent) is a medication or other intervention that reduces anxiety. This effect is in contrast to anxiogenic agents which increase anxiety. Anxiolytic medications are used for the treatment of anxiet ...
, and
sedative when inhaled or ingested.
Structure
The molecule adopts a
tetrahedral molecular geometry with C
3v symmetry.
Natural occurrence
The total global flux of chloroform through the environment is approximately tonnes per year, and about 90% of emissions are natural in origin. Many kinds of
seaweed produce chloroform, and
fungi
A fungus ( : fungi or funguses) is any member of the group of eukaryotic organisms that includes microorganisms such as yeasts and molds, as well as the more familiar mushrooms. These organisms are classified as a kingdom, separately from ...
are believed to produce chloroform in soil. Abiotic processes are also believed to contribute to natural chloroform productions in soils although the mechanism is still unclear.
Chloroform volatilizes readily from soil and surface water and undergoes degradation in air to produce
phosgene,
dichloromethane,
formyl chloride,
carbon monoxide
Carbon monoxide (chemical formula CO) is a colorless, poisonous, odorless, tasteless, flammable gas that is slightly less dense than air. Carbon monoxide consists of one carbon atom and one oxygen atom connected by a triple bond. It is the simple ...
,
carbon dioxide
Carbon dioxide ( chemical formula ) is a chemical compound made up of molecules that each have one carbon atom covalently double bonded to two oxygen atoms. It is found in the gas state at room temperature. In the air, carbon dioxide is trans ...
, and
hydrogen chloride. Its
half-life in air ranges from 55 to 620 days.
Biodegradation in water and soil is slow. Chloroform does not significantly bioaccumulate in aquatic organisms.
History
Chloroform was synthesized independently by several investigators circa 1831:
*Moldenhawer, a German pharmacist from
Frankfurt an der Oder
Frankfurt (Oder), also known as Frankfurt an der Oder (), is a city in the German state of Brandenburg. It has around 57,000 inhabitants, is one of the easternmost cities in Germany, the fourth-largest city in Brandenburg, and the largest German ...
, appears to have produced chloroform in 1830 by mixing
chlorinated lime with
ethanol
Ethanol (abbr. EtOH; also called ethyl alcohol, grain alcohol, drinking alcohol, or simply alcohol) is an organic compound. It is an alcohol with the chemical formula . Its formula can be also written as or (an ethyl group linked to a ...
; he mistook it for ''Chloräther'' (chloric ether,
1,2-dichloroethane), however.
*
Samuel Guthrie, a U.S. physician from
Sackets Harbor, New York
Sackets Harbor (earlier spelled Sacketts Harbor) is a village in Jefferson County, New York, United States, on Lake Ontario. The population was 1,450 at the 2010 census. The village was named after land developer and owner Augustus Sackett, who ...
, also appears to have produced chloroform in 1831 by reacting chlorinated lime with ethanol, as well as noting its
anaesthetic
An anesthetic (American English) or anaesthetic (British English; see spelling differences) is a drug used to induce anesthesia — in other words, to result in a temporary loss of sensation or awareness. They may be divided into two ...
properties; he also believed that he had prepared chloric ether, however.
*
Justus von Liebig carried out the
alkaline cleavage of
chloral
Chloral, also known as trichloroacetaldehyde or trichloroethanal, is the organic compound with the formula Cl3CCHO. This aldehyde is a colourless oily liquid that is soluble in a wide range of solvents. It reacts with water to form chloral hydrate ...
.
*
Eugène Soubeiran obtained the compound by the action of
chlorine bleach on both
ethanol
Ethanol (abbr. EtOH; also called ethyl alcohol, grain alcohol, drinking alcohol, or simply alcohol) is an organic compound. It is an alcohol with the chemical formula . Its formula can be also written as or (an ethyl group linked to a ...
and
acetone
Acetone (2-propanone or dimethyl ketone), is an organic compound with the formula . It is the simplest and smallest ketone (). It is a colorless, highly volatile and flammable liquid with a characteristic pungent odour.
Acetone is miscib ...
.
*In 1834, French chemist
Jean-Baptiste Dumas determined chloroform's empirical formula and named it. In 1835, Dumas prepared the substance by the alkaline cleavage of
trichloroacetic acid
Trichloroacetic acid (TCA; TCAA; also known as trichloroethanoic acid) is an analogue of acetic acid in which the three hydrogen atoms of the methyl group have all been replaced by chlorine atoms. Salts and esters of trichloroacetic acid are calle ...
.
Regnault prepared chloroform by
chlorination Chlorination may refer to:
* Chlorination reaction
In chemistry, halogenation is a chemical reaction that entails the introduction of one or more halogens into a compound. Halide-containing compounds are pervasive, making this type of transform ...
of
chloromethane
Chloromethane, also called methyl chloride, Refrigerant-40, R-40 or HCC 40, is an organic compound with the chemical formula . One of the haloalkanes, it is a colorless, odorless, flammable gas. Methyl chloride is a crucial reagent in industrial ...
.
*In 1842,
Robert Mortimer Glover in London discovered the anaesthetic qualities of chloroform on laboratory animals.
*In 1847, Scottish obstetrician
James Y. Simpson was the first to demonstrate the anaesthetic properties of chloroform on humans, provided by local pharmacist
William Flockhart
William Flockhart, L.R.C.S.E. (1808 – 1871) was a Scottish chemist, a pharmacist who provided chloroform to Doctor (later Sir) James Young Simpson for his anaesthesia experiment at 52 Queen Street, Edinburgh on 4 November 1847. This was the f ...
of Duncan, Flockhart and company,
and helped to popularise the drug for use in medicine.
By the 1850s, chloroform was being produced on a commercial basis, in Britain about 750,000 doses a week by 1895, by using the Liebig procedure, which retained its importance until the 1960s. Today, chloroform – along with
dichloromethane – is prepared exclusively and on a massive scale by the chlorination of methane and chloromethane.
Production
In industry production, chloroform is produced by heating a mixture of
chlorine
Chlorine is a chemical element with the symbol Cl and atomic number 17. The second-lightest of the halogens, it appears between fluorine and bromine in the periodic table and its properties are mostly intermediate between them. Chlorine i ...
and either
chloromethane
Chloromethane, also called methyl chloride, Refrigerant-40, R-40 or HCC 40, is an organic compound with the chemical formula . One of the haloalkanes, it is a colorless, odorless, flammable gas. Methyl chloride is a crucial reagent in industrial ...
(CH
3Cl) or
methane
Methane ( , ) is a chemical compound with the chemical formula (one carbon atom bonded to four hydrogen atoms). It is a group-14 hydride, the simplest alkane, and the main constituent of natural gas. The relative abundance of methane on Ea ...
(CH
4).
[ At 400–500 °C, a ]free radical halogenation
In organic chemistry, free-radical halogenation is a type of halogenation. This chemical reaction is typical of alkanes and alkyl-substituted aromatics under application of UV light. The reaction is used for the industrial synthesis of chloroform ( ...
occurs, converting these precursors to progressively more chlorinated compounds:
: CH4 + Cl2 → CH3Cl + HCl
:CH3Cl + Cl2 → CH2Cl2 + HCl
:CH2Cl2 + Cl2 → CHCl3 + HCl
Chloroform undergoes further chlorination to yield carbon tetrachloride (CCl4):
:CHCl3 + Cl2 → CCl4 + HCl
The output of this process is a mixture of the four chloromethanes (chloromethane
Chloromethane, also called methyl chloride, Refrigerant-40, R-40 or HCC 40, is an organic compound with the chemical formula . One of the haloalkanes, it is a colorless, odorless, flammable gas. Methyl chloride is a crucial reagent in industrial ...
, dichloromethane, chloroform, and carbon tetrachloride), which can then be separated by distillation
Distillation, or classical distillation, is the process of separating the components or substances from a liquid mixture by using selective boiling and condensation, usually inside an apparatus known as a still. Dry distillation is the heat ...
.[
Chloroform may also be produced on a small scale via the ]haloform reaction
In chemistry, the haloform reaction is a chemical reaction in which a haloform (, where X is a halogen
The halogens () are a group in the periodic table consisting of five or six chemically related elements: fluorine (F), chlorine (Cl), ...
between acetone
Acetone (2-propanone or dimethyl ketone), is an organic compound with the formula . It is the simplest and smallest ketone (). It is a colorless, highly volatile and flammable liquid with a characteristic pungent odour.
Acetone is miscib ...
and sodium hypochlorite
Sodium hypochlorite (commonly known in a dilute solution as bleach) is an inorganic chemical compound with the formula NaOCl (or NaClO), comprising a sodium cation () and a hypochlorite anion (or ). It may also be viewed as the sodium s ...
:
:3 NaClO + (CH3)2CO → CHCl3 + 2 NaOH + CH3COONa
Deuterochloroform
Deuterated chloroform
Deuterated chloroform, also known as chloroform-''d'', is the organic compound with the formula C2HCl3 or . Deuterated chloroform is a common solvent used in NMR spectroscopy. The properties of are virtually identical.
Preparation
Deuterated ch ...
is an isotopologue
In chemistry, isotopologues are molecules that differ only in their isotopic composition. They have the same chemical formula and bonding arrangement of atoms, but at least one atom has a different number of neutrons than the parent.
An exampl ...
of chloroform with a single deuterium atom. CDCl3 is a common solvent used in NMR spectroscopy
Nuclear magnetic resonance spectroscopy, most commonly known as NMR spectroscopy or magnetic resonance spectroscopy (MRS), is a spectroscopic technique to observe local magnetic fields around atomic nuclei. The sample is placed in a magnetic fie ...
. Deuterochloroform is produced by the haloform reaction
In chemistry, the haloform reaction is a chemical reaction in which a haloform (, where X is a halogen
The halogens () are a group in the periodic table consisting of five or six chemically related elements: fluorine (F), chlorine (Cl), ...
, the reaction of acetone (or ethanol) with sodium hypochlorite
Sodium hypochlorite (commonly known in a dilute solution as bleach) is an inorganic chemical compound with the formula NaOCl (or NaClO), comprising a sodium cation () and a hypochlorite anion (or ). It may also be viewed as the sodium s ...
or calcium hypochlorite.[ The haloform process is now obsolete for the production of ordinary chloroform. Deuterochloroform can be prepared by the reaction of sodium deuteroxide with ]chloral hydrate
Chloral hydrate is a geminal diol with the formula . It is a colorless solid. It has limited use as a sedative and hypnotic pharmaceutical drug. It is also a useful laboratory chemical reagent and precursor. It is derived from chloral (trichl ...
.
Inadvertent formation of chloroform
The haloform reaction can also occur inadvertently in domestic settings. Bleaching with hypochlorite generates halogenated compounds in side reactions; chloroform is the main byproduct. Sodium hypochlorite solution ( chlorine bleach) mixed with common household liquids such as acetone
Acetone (2-propanone or dimethyl ketone), is an organic compound with the formula . It is the simplest and smallest ketone (). It is a colorless, highly volatile and flammable liquid with a characteristic pungent odour.
Acetone is miscib ...
, methyl ethyl ketone, ethanol
Ethanol (abbr. EtOH; also called ethyl alcohol, grain alcohol, drinking alcohol, or simply alcohol) is an organic compound. It is an alcohol with the chemical formula . Its formula can be also written as or (an ethyl group linked to a ...
, or isopropyl alcohol
Isopropyl alcohol (IUPAC name propan-2-ol and also called isopropanol or 2-propanol) is a colorless, flammable organic compound with a pungent alcoholic odor. As an isopropyl group linked to a hydroxyl group ( chemical formula ) it is the s ...
can produce some chloroform, in addition to other compounds such as chloroacetone or dichloroacetone.
Uses
In terms of scale, the most important reaction of chloroform is with hydrogen fluoride to give monochlorodifluoromethane (CFC-22), a precursor in the production of polytetrafluoroethylene ( Teflon):
:CHCl3 + 2 HF → CHClF2 + 2 HCl
The reaction is conducted in the presence of a catalytic
Catalysis () is the process of increasing the rate of a chemical reaction by adding a substance known as a catalyst (). Catalysts are not consumed in the reaction and remain unchanged after it. If the reaction is rapid and the catalyst recyc ...
amount of mixed antimony halides. Chlorodifluoromethane is then converted into tetrafluoroethylene, the main precursor to Teflon. Before the Montreal Protocol, chlorodifluoromethane (designated as R-22) was also a popular refrigerant.
Solvent
The hydrogen
Hydrogen is the chemical element with the symbol H and atomic number 1. Hydrogen is the lightest element. At standard conditions hydrogen is a gas of diatomic molecules having the formula . It is colorless, odorless, tasteless, non-toxic ...
attached to carbon
Carbon () is a chemical element with the symbol C and atomic number 6. It is nonmetallic and tetravalent—its atom making four electrons available to form covalent chemical bonds. It belongs to group 14 of the periodic table. Carbon mak ...
in chloroform participates in hydrogen bonding. Worldwide, chloroform is also used in pesticide formulations, as a solvent
A solvent (s) (from the Latin '' solvō'', "loosen, untie, solve") is a substance that dissolves a solute, resulting in a solution. A solvent is usually a liquid but can also be a solid, a gas, or a supercritical fluid. Water is a solvent for ...
for fat
In nutrition, biology, and chemistry, fat usually means any ester of fatty acids, or a mixture of such compounds, most commonly those that occur in living beings or in food.
The term often refers specifically to triglycerides (triple est ...
s, oil
An oil is any nonpolar chemical substance that is composed primarily of hydrocarbons and is hydrophobic (does not mix with water) & lipophilic (mixes with other oils). Oils are usually flammable and surface active. Most oils are unsaturated ...
s, rubber
Rubber, also called India rubber, latex, Amazonian rubber, ''caucho'', or ''caoutchouc'', as initially produced, consists of polymers of the organic compound isoprene, with minor impurities of other organic compounds. Thailand, Malaysia, an ...
, alkaloids, wax
Waxes are a diverse class of organic compounds that are lipophilic, malleable solids near ambient temperatures. They include higher alkanes and lipids, typically with melting points above about 40 °C (104 °F), melting to giv ...
es, gutta-percha
Gutta-percha is a tree of the genus ''Palaquium'' in the family Sapotaceae. The name also refers to the rigid, naturally biologically inert, resilient, electrically nonconductive, thermoplastic latex derived from the tree, particularly from ...
, and resin
In polymer chemistry and materials science, resin is a solid or highly viscous substance of plant or synthetic origin that is typically convertible into polymers. Resins are usually mixtures of organic compounds. This article focuses on n ...
s, as a cleansing agent, grain fumigant
Fumigation is a method of pest control or the removal of harmful micro-organisms by completely filling an area with gaseous pesticides—or fumigants—to suffocate or poison the pests within. It is used to control pests in buildings (s ...
, in fire extinguishers
A fire extinguisher is a handheld active fire protection device usually filled with a dry or wet chemical used to extinguish or control small fires, often in emergencies. It is not intended for use on an out-of-control fire, such as one which ha ...
, and in the rubber industry. CDCl3 is a common solvent used in NMR spectroscopy
Nuclear magnetic resonance spectroscopy, most commonly known as NMR spectroscopy or magnetic resonance spectroscopy (MRS), is a spectroscopic technique to observe local magnetic fields around atomic nuclei. The sample is placed in a magnetic fie ...
.
Lewis acid
In solvents such as CCl4 and alkanes, chloroform hydrogen bonds to a variety of Lewis bases. HCCl3 is classified as a hard acid and the ECW model lists its acid parameters as EA = 1.56 and CA = 0.44.
Reagent
As a reagent, chloroform serves as a source of the dichloro carbene :CCl2 group. It reacts with aqueous sodium hydroxide usually in the presence of a phase transfer catalyst
In chemistry, a phase-transfer catalyst or PTC is a catalyst that facilitates the transition of a reactant from one phase into another phase where reaction occurs. Phase-transfer catalysis is a special form of heterogeneous catalysis. Ionic rea ...
to produce dichlorocarbene
Dichlorocarbene is the reactive intermediate with chemical formula CCl2. Although this chemical species has not been isolated, it is a common intermediate in organic chemistry, being generated from chloroform. This bent diamagnetic molecule rapidly ...
, :CCl2. This reagent effects ortho-formylation of activated aromatic rings
In chemistry, aromaticity is a chemical property of cyclic ( ring-shaped), ''typically'' planar (flat) molecular structures with pi bonds in resonance (those containing delocalized electrons) that gives increased stability compared to saturat ...
such as phenols
In organic chemistry, phenols, sometimes called phenolics, are a class of chemical compounds consisting of one or more hydroxyl groups (— O H) bonded directly to an aromatic hydrocarbon group. The simplest is phenol, . Phenolic compounds are ...
, producing aryl aldehyde
In organic chemistry, an aldehyde () is an organic compound containing a functional group with the structure . The functional group itself (without the "R" side chain) can be referred to as an aldehyde but can also be classified as a formyl grou ...
s in a reaction known as the Reimer–Tiemann reaction. Alternatively, the carbene can be trapped by an alkene to form a cyclopropane derivative. In the Kharasch addition, chloroform forms the CHCl2 free radical in addition to alkenes.
Anaesthetic
The anaesthetic
An anesthetic (American English) or anaesthetic (British English; see spelling differences) is a drug used to induce anesthesia — in other words, to result in a temporary loss of sensation or awareness. They may be divided into two ...
qualities of chloroform were first described in 1842 in a thesis by Robert Mortimer Glover, which won the Gold Medal of the Harveian Society for that year. Glover also undertook practical experiments on dogs to prove his theories. Glover further refined his theories and presented them in the thesis for his doctorate at the University of Edinburgh
The University of Edinburgh ( sco, University o Edinburgh, gd, Oilthigh Dhùn Èideann; abbreviated as ''Edin.'' in post-nominals) is a public research university based in Edinburgh, Scotland. Granted a royal charter by King James VI in 15 ...
in the summer of 1847. The Scottish obstetrician
Obstetrics is the field of study concentrated on pregnancy, childbirth and the postpartum period. As a medical specialty, obstetrics is combined with gynecology under the discipline known as obstetrics and gynecology (OB/GYN), which is a surgic ...
James Young Simpson was one of the persons required to read the thesis, but later claimed to have never read the thesis and to have come to his conclusions independently.
On 4 November 1847, Simpson first discovered the anaesthetic qualities of chloroform on humans. He and two colleagues were entertaining themselves by trying the effects of various substances, and thus revealed the potential for chloroform in medical procedures.
A few days later, during the course of a dental procedure in Edinburgh
Edinburgh ( ; gd, Dùn Èideann ) is the capital city of Scotland and one of its 32 council areas. Historically part of the county of Midlothian (interchangeably Edinburghshire before 1921), it is located in Lothian on the southern shore of t ...
, Francis Brodie Imlach became the first person to use chloroform on a patient in a clinical context.
In May 1848, Robert Halliday Gunning made a presentation to the Medico-Chirurgical Society of Edinburgh following a series of laboratory experiments on rabbits that confirmed Glover's findings and also refuted Simpson's claims of originality. A knighthood
A knight is a person granted an honorary title of knighthood by a head of state (including the Pope) or representative for service to the monarch, the church or the country, especially in a military capacity. Knighthood finds origins in the ...
for Simpson, and massive media coverage of the wonders of chloroform, ensured that Simpson's reputation remained high. The laboratory experiments proving the dangers of chloroform were largely ignored.
The use of chloroform during surgery expanded rapidly thereafter in Europe. In the 1850s, chloroform was used by the physician John Snow during the birth of Queen Victoria
Victoria (Alexandrina Victoria; 24 May 1819 – 22 January 1901) was Queen of the United Kingdom of Great Britain and Ireland from 20 June 1837 until her death in 1901. Her reign of 63 years and 216 days was longer than that of any previo ...
's last two children. In the United States, chloroform began to replace ether as an anesthetic at the beginning of the 20th century; it was quickly abandoned in favor of ether upon discovery of its toxicity, however, especially its tendency to cause fatal cardiac arrhythmia analogous to what is now termed " sudden sniffer's death". Some people used chloroform as a recreational drug or to attempt suicide. One possible mechanism of action for chloroform is that it increases movement of potassium ions through certain types of potassium channel
Potassium channels are the most widely distributed type of ion channel found in virtually all organisms. They form potassium-selective pores that span cell membranes. Potassium channels are found in most cell types and control a wide variety of c ...
s in nerve cells. Chloroform could also be mixed with other anaesthetic agents such as ether to make C.E. mixture, or ether and alcohol to make A.C.E. mixture.
In 1848, Hannah Greener, a 15-year-old girl who was having an infected toenail removed, died after being given the anaesthetic. Her autopsy establishing the cause of death was undertaken by John Fife assisted by Robert Mortimer Glover.[ A number of physically fit patients died after inhaling it. In 1848, however, John Snow developed an inhaler that regulated the dosage and so successfully reduced the number of deaths.
The opponents and supporters of chloroform were mainly at odds with the question of whether the complications were solely due to respiratory disturbance or whether chloroform had a specific effect on the heart. Between 1864 and 1910, numerous commissions in Britain studied chloroform but failed to come to any clear conclusions. It was only in 1911 that Levy proved in experiments with animals that chloroform can cause cardiac fibrillation. The reservations about chloroform could not halt its soaring popularity. Between 1865 and 1920, chloroform was used in 80 to 95% of all narcoses performed in the UK and German-speaking countries. In the United States, however, there was less enthusiasm for chloroform narcosis. In Germany, the first comprehensive surveys of the fatality rate during anaesthesia were made by Gurlt between 1890 and 1897. In 1934, Killian gathered all the statistics compiled until then and found that the chances of suffering fatal complications under ether were between 1:14,000 and 1:28,000, whereas under chloroform the chances were between 1:3,000 and 1:6,000. The rise of gas anaesthesia using ]nitrous oxide
Nitrous oxide (dinitrogen oxide or dinitrogen monoxide), commonly known as laughing gas, nitrous, or nos, is a chemical compound, an oxide of nitrogen with the formula . At room temperature, it is a colourless non-flammable gas, and has ...
, improved equipment for administering anaesthetics and the discovery of hexobarbital in 1932 led to the gradual decline of chloroform narcosis.
Criminal use
Chloroform has reputedly been used by criminals to knock out, daze, or even murder victims. Joseph Harris was charged in 1894 with using chloroform to rob people. Serial killer H. H. Holmes used chloroform overdoses to kill his female victims. In September 1900, chloroform was implicated in the murder of the U.S. businessman William Marsh Rice, the namesake of the institution now known as Rice University. Chloroform was deemed a factor in the alleged murder of a woman in 1991 when she was asphyxiated while sleeping. In 2002, 13-year-old Kacie Woody was sedated with chloroform when she was abducted by David Fuller and during the time that he had her, before he shot and killed her. In a 2007 plea bargain, a man confessed to using stun guns and chloroform to sexually assault minors.
Use of chloroform as an incapacitating agent has become widely recognized, bordering on clichéd, due to the popularity of crime fiction authors having criminals use chloroform-soaked rags to render victims unconscious. Nonetheless, it is nearly impossible to incapacitate someone using chloroform in this manner. It takes at least five minutes of inhaling an item soaked in chloroform to render a person unconscious. Most criminal cases involving chloroform also involve another drug being co-administered, such as alcohol or diazepam
Diazepam, first marketed as Valium, is a medicine of the benzodiazepine family that acts as an anxiolytic. It is commonly used to treat a range of conditions, including anxiety, seizures, alcohol withdrawal syndrome, muscle spasms, insomnia, ...
, or the victim being found to have been complicit in its administration. After a person has lost consciousness due to chloroform inhalation, a continuous volume must be administered, and the chin must be supported to keep the tongue from obstructing the airway, a difficult procedure typically requiring the skills of an anesthesiologist. In 1865 as a direct result of the criminal reputation chloroform had gained, the medical journal '' The Lancet'' offered a "permanent scientific reputation" to anyone who could demonstrate "instantaneous insensibility", i.e. losing consciousness instantaneously, using chloroform.
Safety
Exposure
Chloroform is known to form as a by-product of water chlorination along with a range of other disinfection by-products and as such is commonly present in municipal tap water and swimming pools. Reported ranges vary considerably but are generally below the current health standard for total trihalomethanes
In chemistry, trihalomethanes (THMs) are chemical compounds in which three of the four hydrogen atoms of methane () are replaced by halogen atoms. Many trihalomethanes find uses in industry as solvents or refrigerants. THMs are also environ ...
of 100μg/L. Nonetheless, the presence of chloroform in drinking water at any concentration is considered controversial by some.
Historically, chloroform exposure may well have been higher due to its common use as an anaesthetic, as an ingredient in cough syrups, and as a constituent of tobacco smoke
Tobacco smoke is a sooty aerosol produced by the incomplete combustion of tobacco during the smoking of cigarettes and other tobacco products. Temperatures in burning cigarettes range from about 400 °C between puffs to about 900 °C d ...
where DDT
Dichlorodiphenyltrichloroethane, commonly known as DDT, is a colorless, tasteless, and almost odorless crystalline chemical compound, an organochloride. Originally developed as an insecticide, it became infamous for its environmental impacts. ...
had previously been used as a fumigant
Fumigation is a method of pest control or the removal of harmful micro-organisms by completely filling an area with gaseous pesticides—or fumigants—to suffocate or poison the pests within. It is used to control pests in buildings (s ...
.
Pharmacology
It is well absorbed, metabolized, and eliminated rapidly by mammals after oral, inhalation, or dermal exposure. Accidental splashing into the eyes has caused irritation. Prolonged dermal exposure can result in the development of sores as a result of defatting. Elimination is primarily through the lungs in the form of chloroform and carbon dioxide; less than 1% is excreted in the urine.
Chloroform is metabolized in the liver by the cytochrome P-450
Cytochromes P450 (CYPs) are a superfamily of enzymes containing heme as a cofactor that functions as monooxygenases. In mammals, these proteins oxidize steroids, fatty acids, and xenobiotics, and are important for the clearance of various compo ...
enzymes, by oxidation to chloromethanol and by reduction to the dichloromethyl free radical
A daughter category of ''Ageing'', this category deals only with the biological aspects of ageing.
Ageing
Ailments of unknown cause
Biogerontology
Biological processes
Causes of death
Cellular processes
Gerontology
Life extension
Metabo ...
. Other metabolites of chloroform include hydrochloric acid
Hydrochloric acid, also known as muriatic acid, is an aqueous solution of hydrogen chloride. It is a colorless solution with a distinctive pungent smell. It is classified as a strong acid
Acid strength is the tendency of an acid, symbol ...
and digluathionyl dithiocarbonate, with carbon dioxide
Carbon dioxide ( chemical formula ) is a chemical compound made up of molecules that each have one carbon atom covalently double bonded to two oxygen atoms. It is found in the gas state at room temperature. In the air, carbon dioxide is trans ...
as the predominant end product of metabolism.
Like most other general anesthetics and sedative-hypnotic drugs, chloroform is a positive allosteric modulator for the GABAA receptor. Chloroform causes depression of the central nervous system
The central nervous system (CNS) is the part of the nervous system consisting primarily of the brain and spinal cord. The CNS is so named because the brain integrates the received information and coordinates and influences the activity of all p ...
(CNS), ultimately producing deep coma and respiratory center depression. When ingested, chloroform caused symptoms similar to those seen following inhalation. Serious illness has followed ingestion of . The mean lethal oral dose for an adult is estimated at .
The anesthetic use of chloroform has been discontinued because it caused deaths due to respiratory failure and cardiac arrhythmias. Following chloroform-induced anesthesia, some patients suffered nausea, vomiting, hyperthermia, jaundice, and coma due to hepatic dysfunction. At autopsy, liver necrosis and degeneration have been observed.
Chloroform has induced liver tumor
Liver tumors (also known as hepatic tumors) are abnormal growth of liver cells on or in the liver. Several distinct types of tumors can develop in the liver because the liver is made up of various cell types. Liver tumors can be classified as beni ...
s in mice and kidney tumors in mice and rats. The hepatotoxicity and nephrotoxicity of chloroform is thought to be due largely to phosgene.
Conversion to phosgene
Chloroform converts slowly in air to the extremely poisonous phosgene (COCl2), releasing HCl in the process.
:2 CHCl3 + O2 → 2 COCl2 + 2 HCl
To prevent accidents, commercial chloroform is stabilized with ethanol
Ethanol (abbr. EtOH; also called ethyl alcohol, grain alcohol, drinking alcohol, or simply alcohol) is an organic compound. It is an alcohol with the chemical formula . Its formula can be also written as or (an ethyl group linked to a ...
or amylene, but samples that have been recovered or dried no longer contain any stabilizer. Amylene has been found ineffective, and the phosgene can affect analytes in samples, lipids, and nucleic acids dissolved in or extracted with chloroform. Phosgene and HCl can be removed from chloroform by washing with saturated aqueous carbonate solutions, such as sodium bicarbonate. This procedure is simple and results in harmless products. Phosgene reacts with water to form carbon dioxide
Carbon dioxide ( chemical formula ) is a chemical compound made up of molecules that each have one carbon atom covalently double bonded to two oxygen atoms. It is found in the gas state at room temperature. In the air, carbon dioxide is trans ...
and HCl, and the carbonate salt neutralizes the resulting acid.
Suspected samples can be tested for phosgene using filter paper (treated with 5% diphenylamine
Diphenylamine is an organic compound with the formula (C6H5)2NH. The compound is a derivative of aniline, consisting of an amine bound to two phenyl groups. The compound is a colorless solid, but commercial samples are often yellow due to oxidiz ...
, 5% dimethylaminobenzaldehyde in ethanol
Ethanol (abbr. EtOH; also called ethyl alcohol, grain alcohol, drinking alcohol, or simply alcohol) is an organic compound. It is an alcohol with the chemical formula . Its formula can be also written as or (an ethyl group linked to a ...
, and then dried), which turns yellow in phosgene vapor. There are several colorimetric and fluorometric
Fluorescence spectroscopy (also known as fluorimetry or spectrofluorometry) is a type of electromagnetic spectroscopy that analyzes fluorescence from a sample. It involves using a beam of light, usually ultraviolet light, that excites the electron ...
reagents for phosgene, and it can also be quantified with mass spectrometry.
Regulation
Chloroform is suspected of causing cancer
Cancer is a group of diseases involving abnormal cell growth with the potential to invade or spread to other parts of the body. These contrast with benign tumors, which do not spread. Possible signs and symptoms include a lump, abnormal b ...
(i.e., possibly carcinogenic, IARC Group 2B) as per the International Agency for Research on Cancer (IARC) Monographs
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It is classified as an List of extremely hazardous substances">extremely hazardous substance in the United States as defined in Section 302 of the U.S. Emergency Planning and Community Right-to-Know Act (42 U.S.C. 11002), and is subject to strict reporting requirements by facilities that produce, store, or use it in significant quantities.
Bioremediation of chloroform
Some anaerobic bacteria use chloroform for their respiration, termed organohalide respiration, converting it to dichloromethane.
References
External links
Chloroform "The Molecular Lifesaver"
An article at Oxford University providing facts about chloroform.
*IARC Summaries & Evaluations
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NIST Standard Reference Database
{{Authority control
Endocrine disruptors
Chloroalkanes
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IARC Group 2B carcinogens
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