(C) Peter Meiers - http://www.fluoride-history.de
Fluoride Research in the 19th and early 20th century
Before it was announced for the first time that fluoric acid appeared to contain a new chemical element, "fluorine", some researchers already speculated about any possible biological significance of fluoride. They had good reason to have their focus on bones and teeth, for of all animal and human tissues teeth and bones stand out by their hardness and by their resistance to putrefaction which the soft tissues usually succumb soon after the death of their owner. In primeval times the hard tissues have been used as building materials, as tools and weapons, while there was still no knowledge about what determines their special properties.
Around 1680 the French researcher Papin developed a "digesteur" in which he subjected bones to water boiling at elevated pressure. The resulting gelatinous concoctions later were given soldiers to drink in order to transmit hardness and resistance (1).
In 1758, Hérissant contributed to the knowledge of the chemistry of bones when he treated bones with nitric acid which dissolved lime-like matter (i.e. the minerals) and left a flexible organic substance ("gelatin") that still had the form of the bones. Somewhat later, Hérissant showed a lime-like material to be responsible also for the hardness of shells and corals (1).
(1) Chevreul M.: "Résumé historique des travaux dont la gélatine a été l´objet"; C. R. 71 (1870) 855-872 and 912-927;
During his work on the chemical composition of fluorspar the apothecary Carl Wilhelm Scheele delivered ways to identify fluorspar, i.e. (a): the etching of glass by fumes developed from samples on treatment with sulfuric acid; (b) the release of silica when the gas produced during the etching of glass gets in contact with water; (c) precipitation of fluorspar when the acid released by reaction (a) is led into a tube containing lime water.
Upon treatment of fluorspar with phosphoric acid (to show that fluoric acid is not only formed upon the use of sulfuric acid), Scheele remarked that the residue in the retort (calcium from the fluorspar and phosphate from the added phosphoric acid) behaves like the mineral part of bones which "recently has been shown to be made of phosphoric acid and lime" (1). In consequence of this notice, it was for some time believed that Scheele was the discoverer of the constitution of "bone earth", and Assessor Gahn of Fahlun, the actual discoverer, was so indifferent about his reputation as a discoverer, that he never tried to correct the mistake (2).
(1) Scheele C.W.: "Chemische Untersuchung des Flusspats und dessen Säure", in "Carl Wilhelm Scheele, Sämmtliche physische und chemische Werke, nach dem Tode des Verfassers gesammelt und in deutscher Sprache herausgegeben von D. Sigismund Friedrich Hermbstädt", 1793, Reprint: Dr. Martin Sändig oHG, Niederwalluf 1971, Vol. 2, pp.5-32 (original article published in 1771); Thomson T.: "Chemistry of animal bodies", Edinburgh 1843, p. 235
Phosphate of lime also occurs in nature as "rock phosphate". On treating in a test tube a sample of rock phosphate from Estremadura (Spain) with sulfuric acid, Bertrand Pelletier and Louis Donadei found that -besides muriatic and phosphoric acid- it also contains (bound) fluoric acid which etched the tube (1). Fluorspar ("fluate" of lime) was then the only known solid compound of fluoric acid. As both phosphoric and fluoric acid were bound to one base, calcium, and still nothing was known about the chemical nature of fluoric acid, the authors speculated that fluoric acid might be the product of some modification ("transmutation") of phosphoric acid.
(1) Pelletier B., Donadei L.: "Mémoire sur le phosphate calcaire", Ann. Chim. 7 (1790) 79
Josse (1) summarized the analyses of bones from the viewpoint of a chemist: bones are nothing but an accumulation of a mineral, phosphate of lime, mixed with an organic substance made of gelatin. He then addressed the composition of teeth, more specifically of tooth enamel, as the underlying dentin is essentially bone. Dental enamel, he writes, is white, very fragile, of extreme hardness. Along a fractured area it presents a regular, pronounced crystallization, formed by well-ordered assembling of small brillant crystal needles. In order to check whether the special hardness, as compared to dentin, might just be a consequence of higher density due to closer arrangement, in absence of organic substance, of the constituant inorganic molecules, he secured several specimens of human and animal teeth and separated the enamel from the dentin using Papin´s digesteur. Chemical analyses, which he performed in the laboratory of a medical school, showed the presence of just calcium and phosphate in the enamel samples.
(1) Josse: "Mémoire contenant l´examen physique et chimique des dents", Ann. Chim. 43 (1802) 3
On one of his tours, Count Carlo Morozzo of Italy was shown a fossil skeleton of which he thought it once belonged to an unusually huge elephant. Part of the skeleton had already fallen apart. Among the few pieces that could be saved were fragments of molar teeth, of which Morozzo forwarded one to the Italian chemist Domenico Morichini for a chemical analysis (1,2). It contained organic substance, carbonic acid, fluoric acid (found by the etching of glass test), phosphate and calcium, but Morichini had not yet performed a quantitative analysis.
(1) Morozzo: "Analisi chimica del dente fossile fatta dal Dottor Morecchini", Mem. Mat. Fis. Soc. ital. Sci. (Modena) 10:1 (1803) 166-172; (2) Klaproth: "Recherches sur l´acide fluorique contenu dans un dent fossile d´élephant", Mém. Acad. Royale Sci. (1807), pp. 136-139, read Nov. 22, 1804
Morichini extended his investigations (1). Unable to estimate phosphate and fluoride separately, he thought that the latter might prevail given the voluminous white pungent fumes developed upon treatment of the sample with sulfuric acid. Like in the fossil elephant molar, he found fluoric acid also in contemporary human teeth and claimed that, here too, this acid is a main component of dental enamel. However, the etching of glass was not as marked with the contemporary teeth as it was with the fossil sample. This he attributed to a higher content in organic matter of the contemporary human teeth, for a somewhat diminished or retarded etching of glass he also observed when he treated a fluorspar - gelatin mixture with sulfuric acid. Morichini supposed that the composition of natural phosphates, e.g those found at Estremadura, Spain, and Marmarosch, Hungary, is similar to that of human and animal hard tissues examined by him and this led him to speculate that the natural phosphate deposits originated from the decomposition of huge accumulations of big animal skeletons.
Joseph Louis Gay-Lussac carried out some additional experiments in collaboration with Morichini. As a result he claimed that the enamel of teeth is especially rich in "fluate" of lime (as the fluoride was called then) and that the canine teeth, which -according to him- consist almost entirely of enamel, contain more of the fluate than the other teeth (2). Since dental enamel was also known to be harder than the dentin, the combined findings were from now on erroneously interpreted to show that the calcium fluoride provides hardness to the teeth. Thus, in a footnote on the chapter "Of Salts", S. Parkes wrote in 1807: "According to one of the last numbers of the "Annales de Chimie", it appears that fluoric acid is found to form part of the human teeth, and is probably combined with lime. It may be conjectured that this was a contrivance of nature, to give more durability to these important organs than they would have had by phosphate of lime only" (4). Rev. David Blair wrote, in 1810, that "the fluate of lime enters into the composition of Derbyshire spar. It also exists in human teeth, forming the enamel, which defends them from decay" (5).
Gay-Lussac (2) and Chenevix (3) took issue with Morichini´s as well as Martin Klaproth´s thought that fluoric acid may be a mere product of a "transmutation" of phosphoric acid: Neither had it been shown that the fluate increased at the cost of the phosphate, nor that fluate can be found at a position formerly held by phosphate (3). However, if one considers it not to be formed within the animal organism by some kind of metabolism, but taken in with food, it should be found in food materials too (2).
(1) Morichini D.: "Analisi dello smalto di un dente fossile di elefante e die denti umani. Memoria di Domenico Morichini presentata da Giachino Pessuti", Mem. Mat. Fis. Soc. ital. Sci. (Modena) 12:2 (1805) 73-88 and 268-269; (2) Gay-Lussac: "Lettre de M. Gay-Lussac à M. Berthollet sur la présence de l´acide fluorique dans les substances animales, et sur la pierre alumineuse de la Tolfa", Ann. Chim. 55 (1805) 258; also: "Letter of M. Gay-Lussac to M. Berthollet on the presence of fluoric acid in animal substances", Phil. Mag. 23 (1805/1806) 264-8; (3) Chenevix: "Note sur une opinion de M. Klaproth", Ann. Chim. 54 (1805) 207; (4) Parkes S.: "Chymical catechism. Application of Chymistry to the arts for the use of young people, artists, tradesmen, and the amusement of leisure hours", Philadelphia, 1807, p. 157; (5) Blair D.: "Grammar of the principles and practice of chemistry fore the use of schools", 4th edition, London, 1810, p. 133;
Another test: after ashing, recent samples of neither tooth enamel nor bones revealed the slightest traces of fluoric acid, in contrast to fossil samples which show up to three or four per cent, at the most (1). Relative to the voluminous white pungent fumes sometimes observed upon treatment of samples with sulfuric acid, Fourcroy and Vauquelin remarked that such fumes easily develop from the sulfuric acid itself when it is heated. They further suggested that fossil samples may have taken up the "fluate" from their environment, soils or plants, where it still ought to be detected. William Brande, too, was not able to find fluoric acid in recent human tooth enamel, but showed that it consists chiefly of phosphate of lime as previously proved by Hatchett and Josse. Brande showed the fumes arising from sulfuric acid treatment to be made partly of sulfuric acid gas and to partly result from the decomposition (reduction) of the sulfuric acid by animal matter (even sulphur was found in the retort) (2).
(1) Fourcroy, Vauquelin: "Expériences faites sur l´ivoire frais, sur l´ivoire fossile et sur l´émail des dents, pour re-chercher si ces substances contiennent de l´acide fluorique", Ann. Chim. 57 (1806) 37; (2) Brande W.: "Experiments showing, contrary to the assertions of Morichini, that the enamel of teeth does not contain fluoric acid", J. Nat. Phil. Chem. Arts 13 (1806) pp. 214-217;
In a letter to Vauquelin, the famous Swedish chemist and physician Jacob Berzelius reported that he was indeed able to detect fluoride in samples of recent bones and teeth. Referring to "Morocchini"´s [sic!] report, Berzelius analyzed recent human and bovine teeth and bones. Besides organic substance, water, calcium, magnesium, sodium, phosphate and carbonate, he found "fluate" in the following amounts (1):
Though the percentages given appear fairly high, fluoride is still far from being a "main" let alone "prevailing" component as claimed by Morichini and Gay-Lussac.
In this same report, Berzelius demonstrated the presence of fluate in human urine (by precipitation with lime water).
(1) Berzelius J. J.: "Extrait d´une lettre de M. Berzelius à M. Vauquelin", Ann. Chim. 61 (1807) 256;
There were still different views regarding the proportions in which calcium and phosphorus (and oxygen) are bound together in calcium phosphate or the "bone phosphate" (1). Different analyses had led to different results, indicating that there are several "calcium phosphates".
(1) Berzelius J.J.: "Untersuchungen über die Zusammensetzung der Phosphorsäure, der phosphorigen Säure und ihrer Salze", Gilberts Ann. Phys. Chem. 53 (1816) 393-446, 54 (1816) 31-55
Wenzel Krimer speculated that dilute fluoric acid might dissolve in the digestive tract any accidentally swallowed pieces of glass (1). To test the acid´s toxic properties suggested by Thénard´s observations, he ingested a few drops of dilute solutions of hydrofluoric acid and experienced diverse troubles (itching sensations, warmth, vomiting, obstipation). He concluded his experiments, but recommended that a dilution of 1:18 could safely be tried in cases of emergency.
(1) Krimer W.: "Beobachtungen und Versuche über das Verschlucken von Glasstücken", Rhein. Jahrb. Med. Chir., II, Bonn 1820, pp. 128-165
By coincidence, Berzelius discovered fluoride (3.3 mg/l calculated as "fluate de chaux") in the water of Carlsbad (1) which flows through granite ground. A glass which he used to cover a platinum beaker in which he treated with nitric acid the dried residue of the water, was etched. Thus far, this was the first find of fluoride in a sample of water. Berzelius later built a mineral water plant where he produced this water (along with others) artificially (2).
(1) Berzelius J.J.: "Extrait d´une lettre de M. Berzelius à M. Berthollet", Ann. Chim. 21 (1822) 246; (2) Rose H.: "Biography of Berzelius" (Berzelius died 7th Aug. 1848), Edinb. New Phil. J. 53 (1852) 189-221 and 54 (1853) 1-28
Relative to his earlier analyses of bones and teeth Berzelius had to admit that the addition of ammonia ("to complete the precipitation of calcium salts") to solutions containing a relative excess of lime does not only precipitate the phosphate or fluate "but also the carbonate" (still not heard of "hydroxide"?) and thus leads to erroneous results (1, 2). To remove the "carbonate" from the precipitate he now used to wash it with dilute acetic acid.
(1) Berzelius J. J."Untersuchungen über die Flußspathsäure und deren merkwürdigste Verbindungen", Poggendorff´s Annalen der Physik und Chemie 77 (1824) 1-48; (2) Berzelius J. J.: "Fluorure calcique (fluate de chaux)" in "Traité de chimie", 1er partie - Chimie minérale, 4e Tomé, Bruxelles, 1833, pp. 64-67;
Concluding a series of analyses (wherein fluoride was detected by the etching-of-glass test but estimated by the "indirect method"), Gustav Rose postulated that in certain natural phosphates, the so-called "apatites", there is one "atom" of either the chloride or the fluoride of calcium, or mixtures thereof, bound to three "atoms" of calcium phosphate according to the following formula (1):
CaCh4 + 3 Ca3P2 or CaF4 + 3 Ca3P2
(Obviously there was much to be done concerning the chemical proportions)
Rose was of the opinion that chloride and fluoride are isomorphous and could replace each other in the apatites. (Another important apatite, "Hydroxyapatite", was still unknown. The hydroxy- (= OH) -groups escaped during the preparation of the samples for analysis (i.e. on ashing or on addition of some acid to dissolve the sample) in the form of water.)
(1) Rose G.: "Über die chemische Zusammensetzung der Apatite", Poggendorff´s Ann. Phys. 9 (1827) 185-214
Having realized that his earlier method of estimating the fluoride content of bones was erroneous, the resulting values being much too high (1), Berzelius now stated in his textbook "Traité de chimie" that the hard tissues contain fluoride -calculated as calcium fluoride- up to a few tenths of a percent, at the most (2). However, his corrections apparently became not as widely known as his earlier analyses.
(1) Berzelius J.J.: Lehrbuch der Chemie, translated from Swedish by F. Wöhler, Vol. 4.1, Dresden 1831, pg.445; (2) Berzelius J. J..: "Fluorure calcique (fluate de chaux)" in "Traité de chimie", 1er partie - Chimie minérale, Vol. 4, Brüssel, 1833, pp. 64-67
The etching-of-glass test for the presence of fluorides fails if the sample itself already contains silica. Therefore, the chemist Friedrich Wöhler proposed a new method for fluoride estimation: silica is added to every sample along with sulfuric acid. The whole apparatus containing the mixture is weighed, then heated. The weight loss due to release of gaseous silicon fluoride was assumed to be proportional to the fluoride in the sample. For each part of fluoride, 1.395 parts of silicon fluoride are formed (1). At least with a sample of authentic fluorspar he found this method fairly accurate.
(1) Wöhler F.: footnote 1, p. 87 in "Analyse des Pyrochlors", Poggendorffs Ann. Phys. Chem. 48 (1839) 83-95
In a response to G. Owen Rees, Berzelius announced in his Annual Report on the progress of physical and chemical sciences, that fluoride cannot be claimed to be a necessary constituent of bones; its presence therein is rather accidental, like that of calcium arsenate (1) taken into the body from external sources.
Justus von Liebig, a physician and professor of chemistry at the University of Giessen, Germany, claimed -apparently still under the influence of the early reports by Morichini and Gay-Lussac (1805)- that "in certain cases, calcium fluoride seems to be able to substitute for calcium phosphate in the bones and teeth" (2). The phosphate as stored in teeth and bones is ingested with plants which, in turn, take it from the soil, and this way the soil becomes deprived of important minerals. He therefore recommended to replenish the soil with a fertilizer prepared by digesting powdered bones with dilute sulfuric acid and spraying this solution -after further dilution- to the fields. The sulfuric acid, he claimed, will be neutralized by reaction with the alkaline components of soil (3). Liebig thus became the father of the phosphate fertilizer industry.
(1) Berzelius J.J.: Rapport annuel sur les progrès des sciences physiques et chimiques, présenté le 31 Mars 1840, à l´Académie Royale des Sciences de Stockholm, Paris 1841, pg.331; (2) Liebig J.: "Die organische Chemie in ihrer Anwendung auf Agricultur und Physiologie", Braunschweig 1840, p. 139; (3) Ref. 2, pp. 165 and 180
Girardin and Preisser were unable to find the slightest trace of fluoric acid in recent human and animal bones. "Morichini and Berzelius are, so to speak, the only chemists who claimed its presence in recent bones. We have searched for it in vain, and Klaproth as well as Rees were not more fortunate than we." As fluoride exists in fossil bones, it follows necessarily that it enters them from their environment as the bones in the course of time undergo changes during which some components increase, others diminish, some disappear, while others enter which were not present before, the authors explain (1).
(1) Girardin J., Preisser: "Mémoirs sur les os anciens et fossiles, et sur d´autres résidus solide de la putrefaction", Comptes rendus hebd. 15 (1842) 721
The French dentist Antoine Malagou Désirabode recommended the use of "fluates" (as the fluorides were still called then) for the preparation of dental fillings "as they are known to harden in a humid environment" (1). (The original text contradicts the fanciful translation provided in a book on the history of dentistry by Walter Hoffmann-Axthelm who claims that Désirabode probably was the first to think about a caries - preventive use of fluoride (2))
(1) Désirabode A.M.: "Nouveaux éléments complets de la science et de l´art du dentiste", Paris 1845, p. 409 of the chapter on dental filling materials; (2) Hoffmann-Axthelm W.: "Die Geschichte der Zahnheilkunde", Quintessenz-Verlag, Berlin 1973, p. 308
In view of the contradictory results on fluoride in teeth and bones, the question of the "base excess" arose. What is the "excessive" calcium (the supposed calcium chloride or fluoride in the apatite molecule as defined by Rose) bound to if not to fluoride (or chloride)? W. Heintz (1) examined the calcium to phosphate ratio in some animal and human bones and found that indeed there is more of the base than sufficient to neutralize the phosphoric and carbonic acids. He found no chloride. In the etching-of-glass test, carried out with powdered bone, he obtained clear marks and thus had proof of the presence of fluoride. Its amount he estimated by the "indirect method": he supposed (without quantitative determination) it to be equivalent to the amount required to bind the "base excess" (the "excessive" calcium) and thus he found it in the range of the values reported by the famous Berzelius in 1807 (ignoring the fact that the latter had later admitted his error).
(1) Heintz W.: "Über die chemische Zusammensetzung der Knochen", Poggendorff´s Ann. Phys. Chem. 77 (1849) 267
George Wilson found that "contrary to the universal statement of writers on chemistry" water alone (not only if saturated with carbonic acid) can dissolve fluoride of calcium hitherto thought to be rather insoluble (1). As "barium fluoride is even less soluble", and when precipitated is only dissolved again in a large excess of acid, the author suggested that "fluorides may have been mistaken for sulfates in the analysis of mineral water" (as sulfates are usually determined by precipitation as barium sulfate). He also referred to the objection "which must now lie against the present method of determining the quantity of fluorine present in bodies, consisting, as it does, in converting that element into fluoride of calcium, which in the course of the necessary analytical operations, is washed freely, and must be sensibly diminished in quantity; a fact which has of necessity been hitherto overlooked." Wilson found fluoride in several waters, in sea-water, in plants, urine, blood and milk.
(1) Wilson G.: "On the solubility of fluoride of calcium in water, and the relation of this property to the occurrence of that substance in minerals, and in recent and fossil plants and animals", Proc. Royal Soc. Edinburgh 2 (1851) 91
In papers read on April 19, 1852, before the Royal Society of Edinburgh (1), and in July 1852 before the Botanical Society of Edinburgh (2) Wilson presented new methods for the detection of fluoride in the presence of silica which usually makes recognition of fluoride very difficult (1). In the presence of silica (either natural or after mixing the sample with powdered quartz or glass, as proposed by Wöhler in 1839) silicon fluoride is evolved upon addition of sulfuric acid to the sample. The gaseous fluoride is driven off by boiling and conducted into water (where the silica precipitates). The resulting solution is neutralized with ammonia, evaporated to dryness; the soluble fluoride is washed out with water (to separate it from the insoluble silica), again dried and used for the etching-of-glass test. This way Wilson found fluoride in the ashes of many plants previously reported to be free of fluoride, as well as in coal, granite, basalt, topaz, fossil bones, charcoal ash, and hay. It "occurs in marked quantity in the siliceous stems of the Gramineae and Equisetaceae" but even in the plant ashes which contain it most abundantly it "does not probably amount to more than a fraction per cent of their weight. The proportion of fluorine appears to be variable, for different specimens of the same plant did not yield concordant results" (2). Regarding the sources of fluoride in plants he mentioned simple fluorides, such as calcium fluoride, which are water soluble and are carried into the tissues of plants, as well as "compounds of fluorides with other salts, of which the most important is probably the combination of phosphate of lime with fluoride of calcium. This occurs in the mineral kingdom in apatite and phosphorite, and in the animal kingdom in bones, shells, and corals, as well as in blood, milk and other fluids" (2). "The presence of fluoride in animals may now be fully accounted for; as it not only enters their bodies in the water they drink, but is contained in the vegetable food, by which, directly or indirectly, the whole animal kingdom is sustained" (1)
(1) Wilson G.: "On two new processes for the detection of fluorine when accompanied by silica; and on the presence of fluoride in granite, trap, and other igneous rocks, and in the ashes of recent and fossil plants", Edinb. New Phil. J. 53 (1852) 349; (2) Wilson G. "On the presence of fluorine in the stems of Gramineae, Equisetaceae, and other plants; with some observations on the sources from which vegetables derive this element", Edinb. New Phil. J. 53 (1852) 356
Fluorine was found in fossil bones of Nebraska (1). "Since the analyses of the bones of existing animals indicates but a mere trace of fluorine, it seems more probable that that element has been introduced as fluoride of calcium by infiltration during the gradual process of fossilization, after the manner of pseudomorphism in minerals, the fluoride of calcium gradually replacing the organic matter, as transformation proceeded, than that it should have been an original constituent of the bones of the living animal. Still the subjoined analyses of the enclosing matrix gives no evidence whatever of the existence of fluorine in these deposits now. If the fluorine has really been derived from these deposits, we are forced to the conclusion that it has all been removed by the powers of pseudomorphism. May we not, however, rather look to the saline waters, now common in that country, as the source of the fluorine; or perhaps, to the waters of the lake, bay or estuary, in which the bones may have lain macerating, previous to their long interment?"
(1) N.N.: "Analyses of fossil bones of Nebraska", Edinb. New Phil. J. 55 (1853) 109
Fremy claimed that recent bones contain mainly tribasic calcium phosphate, but he also found magnesium ammonium phosphate, which had not been reported before, as well as very low and variable amounts of fluoride. Fossil bones contain more fluoride, silica in the form of quartz, and far less -or even no- organic substance (1).
On examining a fossil ivory from Russia, Wicke (2) observed a brownish-red layer on the enamel which he identified as iron oxide, the source of which he presumed to be the surrounding soil.
(1) Fremy E.: "Recherches chimiques sur les os", C. R. 39 (1854) 1052; (2) Wicke W.: "Analyse von fossilem Elfenbein", Liebigs Ann. Chem. Pharm. 90 (1854) 100
After the detection of fluoride in the bones and the blood of mammals and birds, in bovine albumin, in bile, saliva, urine, and hair, Jerome Nicklès attributed to fluoride "an importance it never had before in medicine and physiology" (1). These finds, he said, contradict Berzelius´ opinion that fluoride is in no case essential but that its presence in bones is purely incidental. (Actually, no evidence for essentiality was presented by Nicklès, just the apparent ubiquitous occurrence of fluoride led him to his conclusion.)
(1) Nicklès J.: "Présence du fluor dans le sang", C. R. 43 (1856) 885
Doubts were raised if fluoride, especially when it occurs in low amounts, was indeed contained in the samples or rather introduced by contaminated commercial chemicals used for the etching-of- glass test. Jerome Nicklès showed that even steam of boiling distilled water was able to produce what appeared as faint etchings on glass (1). Moreover, he discovered fluoric acid in the commercially available sulfuric acid and concluded that all analyses for fluoride made in the past will necessarily have to be repeated in the light of this find (2). He still found fluoride in bones but in amounts far lower than hitherto claimed. "According to Berzelius 100 g of bone minerals contain 3 g of calcium fluoride; with the new methods of investigation that I announce, one finds that there are barely 5 hundredth grams of the fluoride in one kilogram bone substance" (0.05 g per kg = 0.005% or 50 p.p.m.). Mineral waters contain it sometimes in quite remarkable quantities (3). It occurs in drinking water and vegetables, but in so low amounts that one needs a kg of ashed plant material or some thousand liters of water to detect it therein (2).
(1) Nicklès J.: "Recherche du fluor. Action des acides sur le verre", C. R. 44 (1857) 679; (2) Nicklès J.: "Recherches sur la diffision du fluor", C. R. 45 (1857) 331; (3) Nicklès J.: "Présence du fluor daans les eaux minérales de Plombières, de Vichy et de Contrexéville", C. R. 44 (1857) 783
Felix Hoppe, a physiologist of Tübingen, could not detect any fluoride in the immature tooth enamel of newborn pigs but found it with certainty in the mature enamel of adult pigs, humans and fossil rhinoceros, though in very low percentage. Realizing the need for reliable methods of quantitative fluoride determination, he compared in the etching-of-glass test the different intensities of the obtained marks to those caused by samples of calcium phosphate to which he added known and step-wise increasing amounts of calcium fluoride. With this crude method he was only able to conclude that the amount of fluoride present in the samples of adult tooth enamel must be lower than two percent (1).
(1) Hoppe F.: "Untersuchungen über die Constitution des Zahnschmelzes", Virchows Arch. pathol. Anat. Physiol. 24 (1862) 13-32
Another method used by Zalesky, of Charkow, apparently allowed to go below the two percent mark: he estimated the weight loss (due to formation of gaseous silicon fluoride) of glass plates exposed to the hydrofluoric acid fumes developed from acid-treated samples (1). In samples of ox bone he thus found between 0.26 and 0.34 % fluoride (0.54 to 0.69 % calculated as calcium fluoride), in human bones 0.20 to 0.23 % (0.42 to 0.47 % as calcium fluoride), in fossil rhinoceros enamel 0.28 % (0.59 % calcium fluoride) - surprisingly low but uniform results. Zalesky thought that earlier researchers possibly did not always clean their material and therefore got high variation between samples.
Fresenius modified the procedure proposed by Wöhler in 1839. Instead of weighing the distillation apparatus (which has to have a rather high weight to minimize errors when samples with a low fluoride content are analyzed), he suggested to check the weight gain of a receiver tube in which the distilled gas is collected (2). [It is quite obvious, that here like with the Wöhler method, a lot of precautionary measures are to be taken to make sure that no other gas except silicon fluoride is evolved or collected. An imperfectly ashed sample containing some carbon particles would suffice to produce sulfur dioxide from the sulfuric acid and thus lead to erroneous results. Or carbon dioxide (as carbonate), as well as hydrochloric acid (from chloride) in a sample will lead to erroneous results ...]
(1) Zalesky: "Ueber die Zusammensetzung der Knochen des Menschen und verschiedener Thiere", Medicinisch-chemische Untersuchungen, No. 1, Dr. Felix Hoppe-Seyler (ed.), Berlin 1866, pp. 19-48; (2) Fresenius H.: "Ueber ein neues Verfahren zur Bestimmung des Fluors, namentlich auch in Silicaten", Z. analyt. Chem. 5 (1866) 190-197
In the meantime, pathological changes taking place in bones (like in rickets or osteomalacia), with a relative decrease in inorganic and increase in organic components found more widespread interest. Several researchers who investigated in what way the mineral nutrition might be responsible for the observed changes published contradictory results. Weiske (1,2) found that at least in goats fed foods deprived of either calcium or phosphate the bones still aquire the necessary minerals at the cost of the rest of the body (which may develop severe deficiencies).
(1) Weiske H.: "Ueber den Einfluss von kalk- oder phosphorsäurearmer Nahrung auf die Zusammensetzung der Knochen", Z. Biol. 7 (1871) 179-184, 333-337
In January, 1874, Alvaro Francisco Carlos Reynoso, of Paris, France, filed a patent, "Improvement in medical compounds", on "Elixir" and "Sirup" containing fluoride of potassium, sodium or ammonium (1) . His "elixir", he says, is "invigorating, nutritious, and complemental to food", "fluorated sirup" is "...for infants at the period when the bones and teeth are in process of formation"; it also contains "sugar in sufficient quantity". Reynoso was a Cuban scientist who lived in France for many years.
A Dr. Carl Erhardt of Emmendingen, near Freiburg, Germany, recommended "potassium fluoride for the preservation of the teeth" (2). He claimed that fluoride pastilles were introduced several years ago in England where "dental care is known to be on a high level". He claimed to have made studies on dogs (one dog? With fully erupted teeth?): "A molar tooth was extracted, then the dog was fed for four months with very small doses of potassium fluoride, and after this time the corresponding molar tooth on the opposite side was pulled. On exact examination and measurement the enamel of the latter tooth was found to be thicker and harder, a proof that deposition of the medication had taken place." The so-called Hunter´s pastilles he recommended especially "for children during dentition and for women during pregnancy when the teeth so frequently suffer".
(1) Alvaro Francisco Carlos Reynoso, of Paris, France: "Improvement in medical compounds", US Patent 146,781; filed Jan. 16, 1874, patented Jan. 27, 1874 (see also: Patents on ingestable dental Preparations); (2) Dr. Erhardt: "Kali fluoratum zur Erhaltung der Zähne", Der praktische Arzt, Bd. 15 (1874) 69-70; also: Memorabilien - Mschr. rat. Ärzte 19 (1874) 359, engl. translation published in J. Am. Dent. Assn. 49 (Sept. 1954) 385;
At an annual meeting of the "Centralverein deutscher Zahnärzte", Georg von Langsdorff questioned Erhardt´s results (1), as "according to current state of knowledge dental enamel is formed by an independent enamel organ and is not nourished from the dental pulp through some dentinal channels. The microscope does not reveal any supply vessels emanating from the dentin." However, he had obtained from Erhardt -who was unable to attend- a few notes in which the latter refers to Berzelius´ early analytical results showing in dental enamel about 3% calcium fluoride - which, as Erhardt supposed, "is supplied from outside the body with food". It is quite obvious, according to Erhardt, that enamel is thinner if not enough fluoride is given but that the tooth may be kept healthy for a longer time if more fluoride is supplied. Erhardt´s alleged experiment on a dog was now described this way: "A molar tooth was extracted, the dog was fed for three months with very small doses of calcium fluoride and thereafter the molar tooth on the opposite side was pulled [...]". Dr. Erhardt´s more famous brother, a Dr. Wolfgang Erhardt who then worked for the German Embassy in Rome, Italy, provided, upon request, a positive opinion on his brother´s fluoride pills and, therefore, Langsdorff recommended their use, too.
(1) Langsdorff G.: "Ernährung der Zähne durch künstliche Mittel", Dtsch. Vierteljahresschr. f. Zahnheilkunde 15 (1875) 430-9;
There was no limit, obviously, in the fluoride medication euphoria: Joseph Weller, of Trexlertown (Lehigh County), Pennsylvania developed a medication, containing dilute hydrofluoric acid, for the relief of "functional derangements of the liver and the glandular system of the alimentary canal - such as piles, costiveness, dropsy, diarrhea, kidney disease, and all kindred affections which are the result of bile-poisoned blood, as well as the diseases of the genito-urinary mucous membranes in both sexes ..."(1)
(1) Joseph Weller, of Trexlertown (Lehigh County), Pennsylvania: "Medical Compound", US Patent 311,930; filed Aug. 15, 1884, patented Feb. 10, 1885
Hydrofluoric acid and fluorides were claimed to protect the starch-degrading enzyme diastase against the unfavorable action of lactic and butyric ferments contained in its crude preparations (malt extract). Patents filed by Jean Effront, assigned to the Société Générale de Maltose, of Brussels, accordingly make use of fluoride additions to diastase preparations used for glucose production from starch (1,2).
Since 1888, a French physician, Albert Robin, used to prescribe a fluoride (10 to 100 mgs. a day) to his patients in order to "stop the detrimental effects on the organism of lactic, butyric and other ferments, which block the proper functions of the natural digestive juices: saliva, gastric juice, pancreatic juice" (3).
(1) Société Générale de Maltose, of Brussels: "Verfahren zur Darstellung haltbarer Malzwürze und fester Diastase sowie zur Verzuckerung mittels derselben", German Patent DE 49,141; filed Dec. 18, 1888; patented Sept. 14, 1889; (2) idem :"Verfahren der Verzuckerung und Vergährung unter Anwendung von Fluorwasserstoffsäure und anderen Fluorverbindungen", German Patent DE 55,920; filed Oct. 13, 1889, patented Feb. 21, 1891; US Patent 478,418, "Process of fermenting", issued July 5, 1892; (3) c.f. Grosseron T.: "Le fluorure de sodium appliqué à la conservation des denrées alimentaires", J. Hyg. (Paris), Oct. 25, 1903, pp. 85-87
After a study on the composition of natural phosphates, Henri Lasne concluded that fluorine is not simply mixed to but intimately bound in the natural phosphates. Because of this he attributed to fluorine "an important role in the constitution of natural phosphates", and analogous to phosphorus "an unknown role in vegetation and in all phenomena of life" (1).
Hugo Schulz demonstrated the toxicity of sodium fluoride in feeding experiments on several animal species (2). The primary target for toxic effects seems to be the central and peripheral nervous system.
(1) Lasne H.: "Observations sur l´analyse des phosphates", Bull. Soc. chim. (3 rd series) 2 (1889) 313; (2) Schulz H.: "Untersuchungen über die Wirkung des Fluornatriums und der Flusssäure", Arch. Exp. Pathol. Pharmakol. 25 (1889) 326
Fluorides and silicofluorides (in dilutions of 1 : 1,000) were found to inhibit the development of certain infective germs in vitro, but to stimulate the growth of yeast in far lower concentrations (0.1 mg/l) which fact made them useful as additives in the alcoholic fermentation process (where they were claimed to inhibit the unfavorable action of glycolytic and butyrolytic ferments) (1-5).
(1) Faktor F.: "Über die antiseptische und physiologische Wirkung des Ammoniumsilicofluorides", Chem. Zentralbl. I (1889) 612; (2) Effront J.: "Action des acides minéraux sur le ferment lactique et le ferment butyrique", Bull. Soc. Chim.  4 (1890) 337; (3) Effront J.: "Influence de l´acide fluorhydrique et des fluorures sur l´activité de la levure", Bull. Soc. Chim.  5 (1891) 476; (4) Société Générale de Maltose, of Brussels: "Verfahren zur Herstellung von Preßhefe", German Patent DE 55,921; filed March 8, 1890, patented Feb. 27, 1891; (5) idem : "Verfahren zur Reinigung bzw. zur Konservierung von Hefe", German Patent DE 64143, filed Oct. 20, 1891, patented July 28, 1892
J. Brandl & H. Tappeiner (1) fed sodium fluoride to a dog to see if it is entirely excreted as earlier authors (Schulz 1889) suggested. They found that much of it is stored in the skeleton. The teeth have more fluoride in the roots (0.52, 0.56, 0.79 percent in fresh, dry, ashed samples resp.) than in the crowns (0.27, 0.28, 0.36 percent), which shows that more fluoride is contained in the dentin than in the enamel. As this fluoride is derived from the relatively high amount fed, the result adds further weight to the find that normally fluoride occurs in bones and teeth in such low amounts as could hardly be detected by the quantitative methods then available.
(1) Brandl J., Tappeiner H.: "Ueber die Ablagerung von Fluorverbindungen im Organismus nach Fütterung mit Fluornatrium", Z. Biol. 28 (1891) 518
In a famous "Address on tooth culture" by the English physician Sir James Crichton-Browne, a Victorian Psychiatrist, we find another circumstance contradictory to Erhardt´s (1874) claims (relative to the "high level of dental care in England"): "Now, as regards dental caries, it can be scarcely necessary that I should rehearse to you the evidence that has been adduced to prove that it is now far more prevalent in this country than it has ever hitherto been and that its ravages are more widespread and serious, in the present than in any former generation, about the dental history of which we have records" (1). With regard to fluoride, Crichton-Browne apparently was still heavily influenced by Morichini´s early work, supplemented by the findings of Wilson in the 1850´s: "The late Dr. George Wilson showed that fluorine is more widely distributed in nature than was before this time supposed, but still, as he pointed out, it is but sparingly present where it does occur and the only channels by which it can apparently find its way into the animal economy are through the siliceous stems of grasses and the outer husks of grain, in which it exists in comparative abundance. Analysis has proved that the enamel of the teeth contains more fluorine, in the form of fluoride of calcium, than any other part of the body and fluorine might, indeed, be regarded as the characteristic chemical constituent of this structure, the hardest of all animal tissue and containing 95.5 per cent of salts, against 72 per cent in the dentine. As this is so it is clear that a supply of fluorine, while the development of the teeth is proceeding, is essential to the proper formation of the enamel and that any deficiency in this respect must result in thin and inferior enamel ... I think it well worthy of consideration whether the reintroduction into our diet, and especially into the diet of childbearing women and of children, of a supply of fluorine in some suitable natural form - and what form can be more suitable than that in which it exists in the pellicles of our grain stuffs? - might not do something to fortify the teeth of the next generation." (It is remarkable that the author referred to a possibly useful supply of fluorine "while the development of the teeth is proceeding"!)
In a series of papers presented to the French Academy of Sciences, Adolphe Carnot (2-6) demonstrated the presence of fluoride in fresh and fossil bones and teeth. The method he used took advantage of the low solubility of potassium fluosilicate: the silicon fluoride developed on treatment of a sample with sulfuric acid is conducted into a saturated solution of potassium fluoride where silicon fluoride forms a precipitate of potassium fluosilicate which is separated and weighed (2). His values for fresh material were close to the values found by Zalesky (1866), i.e. a few tenths of a percent (0.35% and 0.37% in human bone, 0.45% to 0.63% in animal bones, 0.43% in dentin and 0.20% in ivory of an elephant), the fluoride content in fossil samples increased with geological age (between 0.9 and 3.8 percent), a fact that can be used to estimate the geological age to which a fossil find belongs.
Also in 1892, T. L. Phipson reported his analysis of a fossil wood found on Ile of Wight - 32.45% phosphoric acid and 3.90% fluoride (7), just like in fluoroapatite.
The low values reported by Carnot were regarded by Gabriel (8) to be within the range of analytical errors inherent to the method used and to essentially support Gabriel´s new analytical data which revealed less than 0.1% fluoride in recent samples; this could very well mean there´s no fluoride at all.
(1) Crichton-Browne J.: "An address on tooth culture", The Lancet (July 2, 1892) 6-10; (2) Carnot A.: "Sur le dosage du fluor", C. R. 114 (1892) 750; (3) Carnot A.: "Recherche du fluor dans différentes variétés de phosphates naturels", C. R. 114 (1892) 1003; (4) Carnot A.: "Recherche du fluor dans les os modernes et les os fossiles", C. R. 114 (1892) 1189; (5) Carnot A.: "Sur la composition des ossements fossiles et la variation de leur teneur en fluor dans les différents étages géologiques", C. R. 115 (1892) 243; (6) Carnot A.: "Sur une application de l´analyse chimique pour fixer l´âge d´ossements humains préhistoriques", C. R. 115 (1892) 337; (7) Phipson T. L.: "Sur une bois fossile contenant du fluor", C. R. 115 (1892) 473; (8) Gabriel S.: "Zur Frage nach dem Fluorgehalt der Knochen und Zähne. Vorläufige Mittheilung", Z. analyt. Chem. 31 (1892) 522
Using Carnot´s method, E. Wrampelmeyer, of Wageningen, analyzed the fluoride contents of sound versus diseased teeth of adults and children. While the fluoride content of diseased teeth of adults (1.18%, 1.14%) was somewhat lower than that of sound teeth (1.36%, 1.37%), the reverse was true in teeth of children (1.55%, 1.24% in diseased teeth; 0.65% in sound teeth). Wrampelmeyer concluded that no conclusion regarding the soundness of the teeth can be drawn from their fluoride content (1).
(1) Wrampelmeyer E.: "Über den Fluorgehalt der Zähne", Z. analyt. Chem. 32 (1893) 550
At the instigation of Weiske, Gabriel addressed the old issue of the fluoride content of bones and teeth. After a preliminary communication in 1892 (1), he published, in 1894, a review of the issue as well as his analytical results which revealed that if there´s any fluoride at all in bones and teeth, it is below 0.1%, and that, therefore, it is definitely of no importance (2). This being the case, another component has to be sought that would bind the "base excess", i. e. the part of the calcium in the bone minerals not bound to phosphate, chloride or carbonate. After careful analysis the solution of the riddle was found in a mixture of phosphates according to the following formula (essentially a hydratized mixture of calcium phosphate and hydroxyapatite):
Ca3(PO4)2 + Ca5HP3O13 + 2 H2O
The two types of water (OH- and H2O) bound in that structure escaped the eyes of earlier investigators because the water was lost during the usual ashing process (which weight loss was then erroneously interpreted as "organic substance") or on dissolving the samples in some acid, whereas Gabriel heated his samples carefully in glycerol (to which some potassium hydroxide had been added) to get rid of organic substance.
(1) Gabriel S.: "Zur Frage nach dem Fluorgehalt der Knochen und Zähne. Vorläufige Mittheilung", Z. analyt. Chem. 31 (1892) 522; (2) Gabriel S.: "Chemische Untersuchungen über die Mineralstoffe der Knochen und Zähne", Hoppe-Seylers Z. physiol. Chem. 18 (1894) 257
Andreas Michel (1), a dentist of the University of Wuerzburg, estimated the fluoride content of sound and carious teeth by Fresenius´ method, which consists in conducting the fumes developed by treatment of the samples with sulfuric acid into a weighted receiver containing water. The weight gain, he supposes, is due to silicon fluoride from which the fluoride content can be calculated. The values found (0.56% to 0.63% in normal, 0.63% to 0.67% in carious teeth) did not show any significant difference in fluoride content between sound and carious teeth.
(1) Michel A.: "Untersuchungen über den Fluorgehalt normaler und cariöser Zähne", Dtsch. Mschr. f. Zahnheilk. 15 (1897) 332
Hempel and Scheffler (1) modified Fresenius´ method to separate carbon dioxide from the silicon fluoride in the course of the procedure. Their comparison of the fluoride content of sound vs. carious teeth revealed 0.19% F- in enamel of carious, 0.33% and 0.52% F- in enamel of sound human teeth.
In the same year, Heinrich Harms (2) published his results obtained with a modification by Brandl of the Fresenius method to remove hydrochloric acid from the fumes. His values were even lower than Gabriel´s, varying between 0.005% and 0.022% fluoride in teeth and bones.
(1) Hempel W., Scheffler W.: "Über eine Methode zur Bestimmung des Fluors neben Kohlensäure und den Fluorgehalt von einigen Zähnen", Z. anorg. Chem. 20 (1899) 1; (2) Harms H.: "Beitrag zur Fluorfrage der Zahn- und Knochenaschen", Z. Biol. 38 (1899) 487
After comparing the method developed by Hempel and Scheffler (1899) with the modification made by Brandl as used by Harms (1899), Brandl and Jodlbauer (1,2) admitted that the higher fluoride values found with Hempel´s method may be more correct because the removal of carbon dioxide from the samples, as done in Brandl´s procedure, might cause some loss of fluoride and would thus explain the very low values found by Harms in 1899.
After earlier reports that sodium fluoride inhibits bacterial metabolism, it came into use as a food preservative. In 1903, Grosseron defended its application for that purpose and concluded: "Sodium fluoride is an indispensable auxiliary to commerce and one cannot prohibit its use without causing to the French industry a damage as considerable as unjustified." (3).
(1) Brandl J., Jodlbauer: "Über den Fluorgehalt der Zähne und Knochen. I. Zur Methode der Fluorbestimmung in Zahn- und Knochenaschen", Z. Biol. 41 (1901) 487; (2) Jodlbauer: "Über den Fluorgehalt der Knochen und Zähne. II.", Z. Biol. 44 (1903) 259; (3) Grosseron T.: "Le fluorure de sodium appliqué à la conservation des denrées alimentaires", J. Hyg. (Paris), Oct. 25, 1903, pp. 85-87
With a paper read before the German Society for Surgery, von Stubenrauch (1) presented preparations of bones and teeth of dogs fed sodium fluoride for some time. He pointed out the anomalous development of teeth, faulty positions, heavy wear, and "a typical caries" (as brown staining was interpreted as typical sign of tooth decay at least since Wedl´s "Pathology of the teeth" was published in 1870).
(1) von Stubenrauch: "Experimentelle Untersuchungen über die Wirkung des Fluornatriums auf den Knochen, speziell den Kieferknochen", Verhandlungen der Deutschen Gesellschaft für Chirurgie, 3. Kongress, Berlin 1904, p. 20
In a paper read in 1907, Albert Deninger, a chemist of Mainz, recommended calcium fluoride pills to prevent not only tooth decay but also appendicitis (because in none of the persons taking his fluoride pills, he says, he could observe a case of appendicitis (1)).
A "Hofzahnarzt" Lohmann of Kassel had quite a new idea on the cause of tooth decay: the ´mucin´, a component of saliva, and its degradation products he viewed as an acid responsible for decay. In his opinion, a special kind of bread ("Schwarzbrot") contains much calcium fluoride which -he said- eminently inhibits putrefaction. He concluded that therefore the consumption of this bread paralyzes the bad action of mucin and its degradation products (3).
(1) Deninger A.: "Das Fluor. Ein Mittel gegen Zahnkrankheiten und vielleicht auch gegen Blinddarmentzündung", Deutsche zahnärztl. Wschr. 10 (1907) 196-198; (2) Deninger A.: "Über die Wirkungen des Fluor auf Zähne und Blinddarm", Dtsch. zahnärztl. Zeitung 6:143 (1907) 5; (3) Lohmann: "Über die Entstehung der Zahnkaries. I.", Dtsch. zahnärztl. Zeitung 6:167 (1907) 2-5;
Alphonse Brissemoret (1-3) regarded calcium fluoride as as an important binding agent for the minerals of bones and teeth. He felt that in order to fulfill its important role and to make up for the daily loss of it in urine, a daily fluoride supplement is needed such as in the recipe of Albert Robin. However, Greve, of Munich, raised doubts whether calcium fluoride would be absorbed to any considerable degree, due to its low solubility (3).
E. Rost (4,5) demonstrated pathological calcifications in and on the bones and joints of dogs fed sodium fluoride for 8 to 12 weeks and thus questioned the safety of fluoride additions to food as a preservative.
(1) Brissemoret A.: "Le fluorure de calcium en therapeutique", Bull. gén. de thér. méd. chim. 156 (1908) 147; (2) Brissemoret A.: "Le fluorure de calcium en thérapeutique", Rev. Int. Méd. Chir. 18 (1908) 352; (3) Greve: "Ueber die neueren Heilmittel des Jahres 1908", Dtsch. zahnärztl. Wschr. 12 (1909) 767; (4) Rost E.: Berichte über den 14. Internationalen Kongress für Hygiene und Demographie, Berlin, Sept. 23-29, 1907, publ. 1908, Vol. 4, p. 166; (5) Rost E.: Zur Toxikologie der Fluoride", Arch. Gewerbepathol. Gewerbehyg. 8 (1937) 256-265
Inspired by Deninger, the Johann Abraham Wülfing chemical and pharmaceutical Company, of Berlin, patented a fluoride preparation from which the substance could be easily absorbed (1). Wülfing proposed to precipitate calcium fluoride adsorbed to e.g. casein or albumin by addition of calcium chloride to a solution of either protein plus sodium fluoride. The fine precipitate, dried consecutively with alcohol and ether, contains about 8 percent calcium fluoride. Wülfing Company became famous for its "Albulactin" baby food and "Kalzan" (a calcium supplement).
(1) German Patent DE 222,716: "Verfahren zur Herstellung leicht resorbierbarer Fluorpräparate", patented June 29, 1909; issued June 2, 1910
Another analysis of teeth performed by Gassmann using Walter Hempel´s method revealed the same "fluoride" values in teeth as found earlier by other researchers using that procedure (i.e. a few tenths of a percent). However, a closer look at the gas driven off and collected in water showed that it is not silicon fluoride, as earlier authors assumed, but mainly hydrogen chloride, from the chloride contained in tooth enamel. Thus it became obvious that fluorine does not play any role in the resistance of teeth towards dental caries, as its actual amount in teeth is insignificant (1).
(1) Gassmann Th.: "Chemische Untersuchungen über die Anwesenheit von Fluor in den Zähnen", Schweiz. Vjschr. Zahnheilk. 20 (1910) 204