Calomel
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Calomel is a mercury
chloride The chloride ion is the anion (negatively charged ion) Cl−. It is formed when the element chlorine (a halogen) gains an electron or when a compound such as hydrogen chloride is dissolved in water or other polar solvents. Chloride s ...
mineral In geology and mineralogy, a mineral or mineral species is, broadly speaking, a solid chemical compound with a fairly well-defined chemical composition and a specific crystal structure that occurs naturally in pure form.John P. Rafferty, ed. (2 ...
with
formula In science, a formula is a concise way of expressing information symbolically, as in a mathematical formula or a ''chemical formula''. The informal use of the term ''formula'' in science refers to the general construct of a relationship betwe ...
Hg2Cl2 (see mercury(I) chloride). The name derives from Greek ''kalos'' (beautiful) and ''melas'' (black) because it turns black on reaction with
ammonia Ammonia is an inorganic compound of nitrogen and hydrogen with the formula . A stable binary hydride, and the simplest pnictogen hydride, ammonia is a colourless gas with a distinct pungent smell. Biologically, it is a common nitrogenous ...
. This was known to
alchemists Alchemy (from Arabic: ''al-kīmiyā''; from Ancient Greek: χυμεία, ''khumeía'') is an ancient branch of natural philosophy, a philosophical and protoscientific tradition that was historically practiced in China, India, the Muslim ...
. Calomel occurs as a secondary mineral which forms as an alteration product in mercury deposits. It occurs with native mercury,
amalgam Amalgam most commonly refers to: * Amalgam (chemistry), mercury alloy * Amalgam (dentistry), material of silver tooth fillings ** Bonded amalgam, used in dentistry Amalgam may also refer to: * Amalgam Comics, a publisher * Amalgam Digital, an in ...
,
cinnabar Cinnabar (), or cinnabarite (), from the grc, κιννάβαρι (), is the bright scarlet to brick-red form of mercury(II) sulfide (HgS). It is the most common source ore for refining elemental mercury and is the historic source for the bri ...
, mercurian
tetrahedrite Tetrahedrite is a copper antimony sulfosalt mineral with formula: . It is the antimony endmember of the continuous solid solution series with arsenic-bearing tennantite. Pure endmembers of the series are seldom if ever seen in nature. Of the t ...
, eglestonite,
terlinguaite Terlinguaite is the naturally occurring mineral with formula Hg2 Cl O. It is formed by the weathering of other mercury-containing minerals. It was discovered in 1900 in the Terlingua District of Brewster County Brewster County is a county l ...
,
montroydite Montroydite is the mineral form of mercury(II) oxide with formula HgO. It is a rare mercury mineral. It was first described for an occurrence in the mercury deposit at Terlingua, Texas and named for Montroyd Sharp who was an owner of the deposit. ...
, kleinite, moschelite, kadyrelite, kuzminite, chursinite, kelyanite,
calcite Calcite is a carbonate mineral and the most stable polymorph of calcium carbonate (CaCO3). It is a very common mineral, particularly as a component of limestone. Calcite defines hardness 3 on the Mohs scale of mineral hardness, based on scratc ...
,
limonite Limonite () is an iron ore consisting of a mixture of hydrated iron(III) oxide-hydroxides in varying composition. The generic formula is frequently written as FeO(OH)·H2O, although this is not entirely accurate as the ratio of oxide to hydroxide ...
and various
clay minerals Clay minerals are hydrous aluminium phyllosilicates (e.g. kaolin, Al2 Si2 O5( OH)4), sometimes with variable amounts of iron, magnesium, alkali metals, alkaline earths, and other cations found on or near some planetary surfaces. Clay minera ...
.The Handbook of Mineralogy
/ref> The type locality is Moschellandsburg, Alsenz-Obermoschel,
Rhineland-Palatinate Rhineland-Palatinate ( , ; german: link=no, Rheinland-Pfalz ; lb, Rheinland-Pfalz ; pfl, Rhoilond-Palz) is a western state of Germany. It covers and has about 4.05 million residents. It is the ninth largest and sixth most populous of the ...
,
Germany Germany,, officially the Federal Republic of Germany, is a country in Central Europe. It is the second most populous country in Europe after Russia, and the most populous member state of the European Union. Germany is situated betwee ...
.


History

The substance later known as calomel was first documented in ancient Persia by medical historian
Rhazes Abū Bakr al-Rāzī (full name: ar, أبو بکر محمد بن زکریاء الرازي, translit=Abū Bakr Muḥammad ibn Zakariyyāʾ al-Rāzī, label=none), () rather than ar, زکریاء, label=none (), as for example in , or in . In m ...
in year 850. Only a few of the compounds he mentioned could be positively identified as calomel, as not every alchemist disclosed what compounds they used in their drugs. Calomel first entered Western medical literature in 1608, when
Oswald Croll Oswald Croll or Crollius (c. 1563 – December 1609) was an alchemist, and professor of medicine at the University of Marburg in Hesse, Germany. A strong proponent of alchemy and using chemistry in medicine, he was heavily involved in writing book ...
wrote about its preparation in his ''Tyroncium Chemicum''. It was not called calomel until 1655, when the name was created by
Théodore de Mayerne Sir Théodore Turquet de Mayerne (28 September 1573 – 22 March 1655) was a Genevan-born physician who treated kings of France and England and advanced the theories of Paracelsus. The Young Doctor Mayerne was born in a Huguenot family in Ge ...
, who had published its preparation and formula in “Pharmacopoeia Londinensis" in 1618. By the 19th century, calomel was viewed as a
panacea In Greek mythology, Panacea (Greek ''Πανάκεια'', Panakeia), a goddess of universal remedy, was the daughter of Asclepius and Epione. Panacea and her four sisters each performed a facet of Apollo's art: * Panacea (the goddess of univers ...
, or miracle drug, and was used against almost every disease, including
syphilis Syphilis () is a sexually transmitted infection caused by the bacterium '' Treponema pallidum'' subspecies ''pallidum''. The signs and symptoms of syphilis vary depending in which of the four stages it presents (primary, secondary, latent, a ...
,
bronchitis Bronchitis is inflammation of the bronchi (large and medium-sized airways) in the lungs that causes coughing. Bronchitis usually begins as an infection in the nose, ears, throat, or sinuses. The infection then makes its way down to the bronchi. ...
,
cholera Cholera is an infection of the small intestine by some strains of the bacterium '' Vibrio cholerae''. Symptoms may range from none, to mild, to severe. The classic symptom is large amounts of watery diarrhea that lasts a few days. Vomiting an ...
, ingrown toenails,
teething Teething is the process by which an infant's first teeth (the deciduous teeth, often called "baby teeth" or "milk teeth") appear by emerging through the gums, typically arriving in pairs. The mandibular central incisors are the first primary te ...
,
gout Gout ( ) is a form of inflammatory arthritis characterized by recurrent attacks of a red, tender, hot and swollen joint, caused by deposition of monosodium urate monohydrate crystals. Pain typically comes on rapidly, reaching maximal intens ...
,
tuberculosis Tuberculosis (TB) is an infectious disease usually caused by '' Mycobacterium tuberculosis'' (MTB) bacteria. Tuberculosis generally affects the lungs, but it can also affect other parts of the body. Most infections show no symptoms, ...
,
influenza Influenza, commonly known as "the flu", is an infectious disease caused by influenza viruses. Symptoms range from mild to severe and often include fever, runny nose, sore throat, muscle pain, headache, coughing, and fatigue. These symptom ...
, and
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 ...
. During the 18th and early 19th centuries pharmacists used it sparingly; but by the late 1840s, it was being prescribed in heroic doses—due in part to the research of
Benjamin Rush Benjamin Rush (April 19, 1813) was a Founding Father of the United States who signed the United States Declaration of Independence, and a civic leader in Philadelphia, where he was a physician, politician, social reformer, humanitarian, educa ...
, who coined the term "heroic dose" to mean about 20 grains taken four times daily. This stance was supported by Dr. Samuel Cartwright, who believed that large doses were “gentlest” on the body. As calomel rose in popularity, more research was done into how it worked. J. Annesley was one of the first to write about the differering effects of calomel when taken in small or large doses. Through experimentation on dogs, Annesley concluded that calomel acted more like a laxative on the whole body rather than acting specifically on the vascular system or liver as previous physicians believed. In 1853, Samuel Jackson described the harmful effects of calomel on children in his publication for Transactions of Physicians of Philadelphia. He noted that calomel had harmful effects causing
gangrene Gangrene is a type of tissue death caused by a lack of blood supply. Symptoms may include a change in skin color to red or black, numbness, swelling, pain, skin breakdown, and coolness. The feet and hands are most commonly affected. If the gan ...
on the skin, loss of teeth, and deterioration of the gums. On May 4, 1863,
William A. Hammond William Alexander Hammond (28 August 1828 – 5 January 1900) was an American military physician and neurologist. During the American Civil War he was the eleventh Surgeon General of the United States Army (1862–1864) and the founder of the A ...
, the United States’ Surgeon-General, stated that calomel would no longer be used in the army as it was being abused by soldiers and physicians alike. This caused much debate in the medical field, and eventually led to his removal as Surgeon-General. Calomel continued to be used well into the 1890s and even into the early 20th century. Eventually calomel’s popularity began to wane as more research was done, and scientists discovered that the mercury in the compound was poisoning patients. Calomel was the main of the three components of the pill number 9 of the British army during the First World War.


Electrochemistry

Calomel is used as the interface between metallic mercury and a chloride solution in a
saturated calomel electrode The saturated calomel electrode (SCE) is a reference electrode based on the reaction between elemental mercury and mercury(I) chloride. It has been widely replaced by the silver chloride electrode, however the calomel electrode has a reputation o ...
, which is used in
electrochemistry Electrochemistry is the branch of physical chemistry concerned with the relationship between electrical potential difference, as a measurable and quantitative phenomenon, and identifiable chemical change, with the potential difference as an out ...
to measure pH and electrical potentials in solutions. In most electrochemical measurements, it is necessary to keep one of the electrodes in an electrochemical cell at a constant potential. This so-called reference electrode allows control of the potential of a working electrode.


Chemical properties

Calomel is a powder that is white when pure. When it is exposed to light or contains impurities it takes on a darker tint. Calomel is made up of mercury and chlorine with the chemical formula Hg2Cl2. Depending on how calomel was administered, it affected the body in different ways. Taken orally, calomel damaged mainly the lining of the gastrointestinal tract. Mercury salts (such as calomel) are insoluble in water and therefore do not absorb well through the wall of the small intestine. Some of the calomel in the digestive system will likely be
oxidized Redox (reduction–oxidation, , ) is a type of chemical reaction in which the oxidation states of substrate change. Oxidation is the loss of electrons or an increase in the oxidation state, while reduction is the gain of electrons or a ...
into a form of mercury that can be absorbed through the intestine, but most of it will not. Oral calomel was actually the safest form of the drug to take, especially in low doses. Most of the calomel ingested will be excreted through urine and stool. Powdered forms of calomel were much more toxic, as their vapors damaged the brain. Once inhaled, the calomel enters the bloodstream and the mercury binds with the
amino acids Amino acids are organic compounds that contain both amino and carboxylic acid functional groups. Although hundreds of amino acids exist in nature, by far the most important are the alpha-amino acids, which comprise proteins. Only 22 alpha am ...
methionine, cysteine, homocysteine and taurine. This is because of the sulfur group these amino acids contain, which mercury has a high affinity for. It is able to pass through the
blood brain barrier Blood is a body fluid in the circulatory system of humans and other vertebrates that delivers necessary substances such as nutrients and oxygen to the cells, and transports metabolic waste products away from those same cells. Blood in the ...
and builds up in the brain. Mercury also has the ability to pass through the
placenta The placenta is a temporary embryonic and later fetal organ that begins developing from the blastocyst shortly after implantation. It plays critical roles in facilitating nutrient, gas and waste exchange between the physically separate mate ...
, causing damage to unborn babies if a pregnant mother is taking calomel. Calomel was manufactured in two ways - sublimation and
precipitation In meteorology, precipitation is any product of the condensation of atmospheric water vapor that falls under gravitational pull from clouds. The main forms of precipitation include drizzle, rain, sleet, snow, ice pellets, graupel and hail. ...
. When calomel first started being manufactured it was done through sublimation. Calomel made through sublimation tends to be a very fine white powder. There was some controversy over the sublimation of calomel. Many argued that the more times calomel was sublimed, the purer it got. Opponents believed that the repeated sublimation made calomel lose some of its therapeutic ability. In 1788 chemist
Carl Wilhelm Scheele Carl Wilhelm Scheele (, ; 9 December 1742 – 21 May 1786) was a Swedish German pharmaceutical chemist. Scheele discovered oxygen (although Joseph Priestley published his findings first), and identified molybdenum, tungsten, barium, hydr ...
came up with the mechanism to make precipitated calomel. This became rapidly popular in the pharmaceutical industry because it was both a cheaper and safer form of production. Precipitation also tended to form very pure calomel salts.


Medicine

Calomel was a popular medicine used during the Victorian period and was widely used as a treatment for a variety of ailments during the American Civil War. The medication was available in two forms, blue pills and blue masses. The blue pill was an oral form of calomel containing mercury that was often mixed with a sweet substance, like licorice or sugar in order to be taken by mouth. The blue mass was a solid form of calomel in which a piece could be pinched off and administered by a physician or other medical provider. Neither form of the medication came with a standardization of dosing. There was no way of knowing how much mercurous chloride each dose contained.


Uses

Calomel was marketed as a purgative agent to relieve congestion and constipation; however, physicians at the time had no idea what the medication’s mechanism of action was. They learned how calomel worked through trial and error. It was observed that small doses of calomel acted as a
stimulant Stimulants (also often referred to as psychostimulants or colloquially as uppers) is an overarching term that covers many drugs including those that increase activity of the central nervous system and the body, drugs that are pleasurable and inv ...
, often leading to bowel movements, while larger doses caused
sedation Sedation is the reduction of irritability or agitation by administration of sedative drugs, generally to facilitate a medical procedure or diagnostic procedure. Examples of drugs which can be used for sedation include isoflurane, diethyl ether, ...
. During the 19th century, calomel was used to treat numerous illnesses and diseases like mumps, typhoid fever, and others—especially those that impact the gastrointestinal tract, such as constipation, dysentery, and vomiting. As mercury softened the gums, calomel was the principal constituent of teething powders until the mid-twentieth century. Babies given calomel for teething often suffered from
acrodynia Acrodynia is a medical condition which occurs due to mercury poisoning. The condition of pain and dusky pink discoloration in the hands and feet is due to exposure or ingesting of mercury. It was known as Pink Disease (due to these symptoms) be ...
.


Side effects

It became popular in the late 18th century to give calomel in extremely high doses, as Benjamin Rush normalized the heroic dose. This caused many patients to experience many painful and sometimes life-threatening side effects. Calomel, in high doses, led to
mercury poisoning Mercury poisoning is a type of metal poisoning due to exposure to mercury. Symptoms depend upon the type, dose, method, and duration of exposure. They may include muscle weakness, poor coordination, numbness in the hands and feet, skin rashes ...
, which had the potential to cause permanent deformities and even death. Some patients experienced
gangrene Gangrene is a type of tissue death caused by a lack of blood supply. Symptoms may include a change in skin color to red or black, numbness, swelling, pain, skin breakdown, and coolness. The feet and hands are most commonly affected. If the gan ...
of the mouth generated by the mercury in the medicine, which caused the tissue on the cheeks and gums inside the mouth to break down and die. Some patients would lose teeth, while others were left with facial deformities. High doses of calomel would often lead to extreme cramping, vomiting, and bloody diarrhea; however, at the time, this was taken as a sign that the calomel was working to purge the system and rid the disease. Calomel was often administered as a treatment for
dysentery Dysentery (UK pronunciation: , US: ), historically known as the bloody flux, is a type of gastroenteritis that results in bloody diarrhea. Other symptoms may include fever, abdominal pain, and a feeling of incomplete defecation. Complications ...
; the effects of calomel would often worsen the severe diarrhea associated with dysentery and acted as a
catalyst 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 ...
in speeding up the effects of dehydration. One victim was Alvin Smith, the eldest brother of
Joseph Smith Joseph Smith Jr. (December 23, 1805June 27, 1844) was an American religious leader and founder of Mormonism and the Latter Day Saint movement. When he was 24, Smith published the Book of Mormon. By the time of his death, 14 years later, h ...
, founder of
the Church of Jesus Christ of Latter-day Saints The Church of Jesus Christ of Latter-day Saints, informally known as the LDS Church or Mormon Church, is a Nontrinitarianism, nontrinitarian Christianity, Christian church that considers itself to be the Restorationism, restoration of the ...
. It was also used by
Charles Darwin Charles Robert Darwin ( ; 12 February 1809 – 19 April 1882) was an English naturalist, geologist, and biologist, widely known for his contributions to evolutionary biology. His proposition that all species of life have descended ...
to treat the severe gastrointestinal infection that presumably began the inductive phase of his documented
Crohn's disease Crohn's disease is a type of inflammatory bowel disease (IBD) that may affect any segment of the gastrointestinal tract. Symptoms often include abdominal pain, diarrhea (which may be bloody if inflammation is severe), fever, abdominal distensi ...
. Eventually, it was determined that calomel was causing more harm than good, as the side effects were often worse than the illness it was being used to treat; because of this, calomel was removed from medical supply shelves.


Citations


General bibliography

* Palache, P.; Berman H.; Frondel, C. (1960). ''Dana's System of Mineralogy, Volume II: Halides, Nitrates, Borates, Carbonates, Sulfates, Phosphates, Arsenates, Tungstates, Molybdates, Etc.'' (Seventh Edition). John Wiley and Sons, Inc., New York, pp. 25–28. {{authority control Halide minerals Mercury(I) minerals Withdrawn drugs