An Introduction to Boron: History,Sources, Uses, and ChemistryWilliam G. WoodsOffice of Environmental Health and Safety, University of California, Riverside, California

Following a brief overview of the terrestrial distribution of boron in rocks, soil, and water, the history of the discovery, early utilization, and geologicorigin of borate minerals is summmarized. Modern uses of borate-mineral concentrates, borax, boric acid, and other refined products include glass,fiberglass, washing products, alloys and metals, fertilizers, wood treatments, insecticides, and microbiocides. The chemistry of boron is reviewedfrom the point of view of its possible health effects. It is concluded that boron probably is complexed with hydroxylated species in biologic systems,and that inhibition and stimulation of enzyme and coenzymes are pivotal in its mode of action. - Environ Health Perspect 102(Suppl 7):5-11 (1994)

Key words: boron, borax, colemanite, glass, boric acid, health effects, enzyme, review

IntroductionBoron is an ubiquitous element in rocks,soil, and water. Most of the earth's soilshave <10 ppm boron, with high concen-

trations found in parts of the western

United States and in other sites stretchingfrom the Mediterranean to Kazakhstan.The average soil boron concentration is10 to 20 ppm, with large areas of theworld boron deficient. Boron concentra-

tions in rocks range from 5 ppm inbasalts to 100 ppm in shales, and averages

10 ppm in the earth's crust overall. Soilshave boron concentrations of 2 to 100ppm. Seawater contains an average of 4.6ppm boron, but ranges from 0.5 to 9.6ppm. Freshwaters normally range from<0.01 to 1.5 ppm, with higher concentra-

tions in regions of high boron soil levels(1,2).

Highly concentrated, economicallysized deposits of boron minerals, alwaysin the form of compounds with boronbonded to oxygen, are rare and generallyare found in arid areas with a history ofvolcanism or hydrothermal activity. Suchdeposits are being exploited in Turkey,the United States, and several other coun-

tries (3). Borate-mineral concentrates

and refined products are produced andsold worldwide. They are used in a myri-ad of ways: in glass and related vitreousapplications, in laundry bleaches, in fire

This paper was presented at the InternationalSymposium on Health Effects of Boron and ItsCompounds held 16-17 September 1992 at theUniversity of California, Irvine, California.

Address correspondence to Dr. William G. Woods,Office of Environmental Health and Safety, Universityof California, Riverside, Riverside, CA 92521.Telephone (909) 687-1568. Fax (909)787-5122.

retardants, as micronutrients in fertilizersand for many other purposes, as well.

The varied chemistry and importanceof boron is dominated by the ability ofborates to form trigonal as well as tetrahe-dral bonding patterns and to create com-plexes with organic functional groups,many of biologic importance.

The present review will give anoverview of boron from its sources to itsuses and chemistry to provide a back-ground for the following papers dealingwith its health effects.

History and SourcesThe Babylonians have been credited withimporting borax from the Far East over4000 years ago for use as a flux for work-ing gold. Mummifying, medicinal andmetallurgic applications of boron aresometimes attributed to the ancientEgyptians. None of this very old boraxhistory has been verified, but solid evi-dence exists that tinkar (i.e.,Na 2B40 7- 10H 20, tincal, the mineralborax) was first used in the eighth centuryaround Mecca and Medina, having beenbrought there (and to China) by Arabtraders (4). The use of borax flux byEuropean goldsmiths dates to about the12th century.

The earliest source of borax is believedto have been Tibetan lakes. The boraxwas transported in bags tied to sheep,which were driven over the Himalayas toIndia.

Volatility of boric acid with steam isbelieved by geologists to be the primarymechanism for the formation of boratedeposits (3). A prime example of this arethe geysers (soffioni) in Tuscany, which

were an important source of boric acid inEurope from about 1820 to the 1950s.Borax also was made from Italian boricacid in England, France, and Germany.

The borate industry in Turkey com-menced in 1865 with mining of the calci-um borate pandermite (priceite,4CaO5B203 7H20). At about the sametime, several borate deposits were foundin California and Nevada, including ulex-ite (Na202CaO 5B 20 3 16H 20) andcolemanite (2CaO3B203 5H20) inDeath Valley. These minerals could beconverted to borax by reaction with trona(Na2CO3-NaHCO 32H 20).

The Kramer deposit, at what is nowBoron, California, in the Mojave Desert,was discovered in 1913, first as a cole-manite ore source. In 1925, tincal ore wasfound and in 1926, the new mineralrasorite (kernite, Na202B20 34H 20)was encountered (4). It is the largestborate deposit outside of Turkey and hassupplied a sizable portion of world boratedemand for over 50 years.

Turkey has supplied colemanite formany years to boric acid producers inEurope. Sodium borates were discoveredat Kirka in 1960 and other deposits havesince been found and developed inAnatolia. As a result, today Turkey is thelargest producer of borate products in theworld (5), exporting mineral concentratesof tincal, colemanite, and ulexite, plusrefined borax decahydrate, borax pen-tahydrate (Na2O°2B203-5H20), anhy-drous borax (Na2O-2B20 3 ), and boricacid (B[OH]3).

Borates in the United States are pro-duced entirely in the Mojave Desert ofsouthern California. United States Borax

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W G. WOODS

Table 2. Estimated consumption of boron mineralsand chemicals in the United States (6).Use Percent

Glass and ceramicsInsulation fiberglass 28Textile fiberglass 12Glass 9Enamels and glazes 3

Detergents and bleaches 12Alloys and metals 6Fire retardants 5Agriculture 4Adhesives 2Other chemicals 19

U..~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~. ....

Figure1 .Aerial view of the US Borax mine and refineryeat Boron CA (U Borax Inc photo)

Figure 1. Aerial view of the US Borax mine and refinery at Boron, CA. (US Borax, Inc. photo)

Table 1. Important refined borate products and mineral concentrates.

Name Formula Percent B203Borax pentahydrate Na2[B405(OH)4] 3H20 47.8Borax (tincal) Na2[B405(OH)4]F8H20 36.5Colemanite Ca[B304(OH)3] H2O 50.8Ulexite NaCa[B506(OH)6]F5H20 43.0Boric acid B(OH)3 56.3Anhydrous borax Na2B407 (glass) 69.2

& Chemical Corporation, a subsidiary ofRio Tinto Zinc (RTZ), is the largestsource, producing borax pentahydrateand decahydrate, and anhydrous boraxfrom tincal ore, and boric acid from ker-nite ore (Equation 1).

Na2B407 4H20+H 2S04 + H204B(OH)3 + Na2SO4 [1]

An aerial photo of the US Borax mineand refinery is shown in Figure 1. AnotherUS Borax plant at Los Angeles harbor pro-duces ammonium and potassium borates,boric oxide, zinc borate, and spray driedpolyborates, in addition to serving as anexport terminal.

North American Chemical recoversborax and boric acid as byproducts frompotash, soda ash, and salt-cake extrac-tion operations on Searles Lake brine.Ore concentrates are produced byNewport Mineral Ventures on the edgeof Death Valley.

Peru and Chile produce ulexite concen-trates and boric acid, and Boroquimica inArgentina operates a tincal deposit. China

and the former USSR also produce someborates.

Table 1 gives a list of the commerciallyimportant refined borate products andmineral concentrates. The formulas arewritten in a form reflecting their structures.

UsesTable 2 lists the uses of boron minerals andchemicals in the United States glass andrelated uses consume about half of theborates as boric anhydride (B203) in theUnited States (6). Fiberglass accounts forthe largest share, comprising about 77% ofthe total (54% for insulation fiberglass,23% for textile grade). Heat-resistant pyrexand other low-thermal expansion glassesconsume about 18%, while enamels, frits,and ceramic glazes consume 5%. Smallamounts are used in sealing and opticalglasses, Vycor, and vitrifying nuclear waste.

Boric oxide can be added to the glassformulation as borax pentahydrate, boricacid, or colemanite, with price and cationcompatibility determining which is used(7). For example, textile fiberglass requires

low sodium, so boric acid or colemanite areused. Glass batch melting is aided by B203which acts as a flux to improve the meltingrate of more refractory components (e.g.,SiO2). As an added benefit, water given offby the borates also accelerates the melting.

The alkali/alkaline earth oxide contentis quite important to the effect of B203 onthe structure and properties of glass.Adding Na2O, for example, progressivelychanges trigonal B03 groupings to tetrahe-dral B04- groups, which initially causes anincrease in the glass transition temperature(Tg). Further addition of Na)O convertsB04- bonding groups to nonbondingBO3-n units, which decreases Tg as well asthe melt viscosity. The latter helps in elimi-nating bubbles from the finished glass andgives good homogeneity and flattens theviscosity-temperature curve. The latterallows more latitude during manufacture(forming) of the finished glass product, andthe lower viscosity allows higher pro-duction rates.

Borosilicate glass has increased thermalshock resistance because B203 lowers theexpansion coefficient. In fiberglass, boricoxide gives desirable drawing qualities andincreases mechanical strength and chemicaldurability.

Another 12% of United States B203 isconsumed in detergents and bleaches; thepercentage is even higher in Europe. Boraxhas been used as a laundry additive sinceabout 1900. It can contribute to the soft-ening of hard water by tying up calciumions, as well as acting as a buffer agent. Atraditional use as a sweetening agent fordiaper pails is thought to involve the borateinhibition of the urease enzyme, (prevent-ing ammonia formation). The same effecthas been patented for deodorizing animallitter (8). Products based on borax and for-mulated with additives can give bleachlikeactivity when added to the wash.

Sodium perborates [NaBO3' 1 H 20 or4H20; PBS1 or PBS4] are true persalts

Environmental Health Perspectives6

INTRODUCTION TO BORON: HISTORY, SOURCES, USES, AND CHEMISTRY

that traditionally have been blended intopowdered detergents in Europe as bleach-ing agents. Dilution in alkaline wash waterresults in hydrolysis of PBS to givehydroperoxide ion (Eq. 2).

HO,

Na2[(HO)2B(OO)2B(OH)2 ]*6H20 + 20H- --

2NaB(OH)4 + 200H- + 4H20[2] B303(O0H)4 B303(OH)S

Sodium perborate (PBS) is effective as abroad-range bleach only at washing tem-peratures above about 60°C, unless an acti-vator is present. Activators are organic acylderivatives, which react with the hydroper-oxide ion formed by hydrolysis of theperborate leading to peracid formation (Eq.3). These peracids are effective bleachingagents at low temperature.

CH3(CH 2)7COO Q S0 3NaSNOBS

or(CH3CO) 2NCH2CH2N(COCH3 )2

TAED

0

HOW

B40s(OH)4 Bs06(OH)

Figure 2. Polymeric borate anions (14).

+ 1 or2-00H-*

CH3(CH2)7COOOH or 2 CH3COOOH[3]

At present, sodium 4-nonanoyloyben-zenesulfonate (SNOBS) is used in severaldetergents with bleach products in theUnited States, and tetraacetylethylenedi-amine (TAED) is used widely in Europe aswell as in many other countries.PBS-based powdered bleach also is sold inthe United States. Borax or boric acid canbe used to stabilize protease enzymes inliquid laundry detergents (9,10).

Alloy and metal production consumeanother 5.5% of the total B203. Weldingrods and other fluxes use borates becauseof their excellent metal oxide solubilizingability. Boron usage in amorphous metalalloys for electrical equipment and mag-nets is slowly increasing. Borates are usedextensively as fire retardants, particularlyborax and boric acid in shredded cellu-losic insulation and zinc borate in plas-tics. Concerns about the toxicity of othertreatments have increased the interest inborates for wood preservation.

Agriculturally, borates are used in fer-tilizer (4% of United States B203) to cor-rect trace boron-deficiency in certain

crops (2). Some crops susceptible toboron deficiency are apples, alfalfa, sugarbeets, and oil palms. Boron is one of themore important essential elements forplant growth, and can be applied either tothe soil or to the foliage. Although smallamounts of boron are needed by allplants, high concentrations can be toxicto certain species. Borates and combina-tions of borates with organic herbicidesare used to control weeds.

The exact role of boron in plant metab-olism is not known. Boron deficiency altersthe plasmalemma of root cells, whichresults in reduced absorption of potassium,chloride, and rubidium, as well as cessationof root growth. Enzymes such as glucansynthetase involved in pollen tube cell wallgrowth apparently require boron. Boronalso may control the amount of phenols incells. Apical meristem abnormalities maybe a secondary effect of vascular tissuedamage caused by lack of boron. An ade-quate supply of boron is essential for prop-er seed set and normal fruit development.Breakdown of parenchyma in cell wallswhich results in reduced lignification isanother symptom of boron starvation.Sugar buildup in leaves of boron-deficientplants is attributed to reduced sugar con-sumption and plasmalemma abnormalitiesinhibiting sugar transport out of the leaves.

Adequate boron is required for incorpora-tion of phosphorus into RNA and DNA.Lack of boron also is suspected of elevatingindoleacetic acid (IAA) in plants byinhibiting IAA oxidase (2).

Borates are used extensively in treatingwood to protect against decay by brownand white rot, and staining by fungi (11).

Insecticidal use of borates is attractivebecause of their low mammalian toxicityand lack of insect resistance compared withthe organic insecticides. The literature con-tains over 150 references in this field.Species showing promise for control byborate-based insecticides are the powderpost beetle (Lyctus brunneus) in hardwoods(12) and larvae of several other beetleswhich attack soft wood. Some species ofsubterranean termites like Coptotermesand Reticulitermes which contain gut pro-tozoa are susceptible, because boron is toxicto these cellulose-digesting organisms andleads to starvation of the host as well as sys-temic effects. Less research has been doneon drywood termites, but some success hasbeen obtained with Cryptotermes. Sodiumoctaborate, a highly soluble polyborate, isof interest both for pre and posttreatmentofwood.

Control of cockroaches with boric acidhas had great success, particularly againstthe German roach Blattella germanica in

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W G. WOODS

B303(OH)4-040

B506(OH) -B0(020

B4OsOHg-0A4 6 8 10

pHFigure 3. Distribution of polyborate species as a function of pH, 0.40M boric acid (15).

H C BO Ca++* o00 0

Figure 4. Diastereomeric borate-saccharate complexes showing calcium coordination (18).the US Boric acid does not act as a repel-lant, (a problem with many organic blatti-cides), and it is inexpensive, safe, and effec-tive (13). When powdered boric acid iscombined with an anticaking agent, theroach contacts the chemical and eventuallydies through cuticular absorption andingestion by grooming.

Promising work also has been done withboron insecticides on ants, carpet beetles,and fleas.

Miscellaneous applications in starchadhesives, raw material for sodium borohy-dride, borides, boron trifluoride, semicon-

tions have been shown by NMR andRaman spectra, as well as by titrimetric evi-dence, to contain polyborate ions of thetypes shown in Figure 2 (14). The distrib-ution of these species as a function ofpH isgiven in Figure 3 (15).

At the pH of human blood (7.4), theexpected low concentrations of borate willbe present as 98.4% B(OH)3 and only1.6% as the B(OH)4- ion because of theweak acidity (PKa 9.2) of boric acid.

Simple alcohols react with boric acid to

give esters (Eq. 4). In aqueous solution,this equilibrium usually lies far to the left.

B(OH)3 + 3ROH -> B(OR)3 + 3H20[4]

The partially esterified species(RO)2BOH and ROB(OH)2 probably alsoare involved (16). Polyhydric alcoholsform cyclic esters with boric acid. Forexample, hexylene glycol boric anhydride(Structure 1)

12 id

Structure 1

and 1,3-butylene glycol biborate (Structure2)

o 0

0'~~~

Structure 2

are mixed to give the jet fuel microbiocideBiobor JF. This additive prevents thegrowth of Cladosporium resinae andPseudomonas aeruginosa in fuel tanks bydistributing itself between the water andfuel phases. This hydrocarbon-metaboliz-ing fungus and bacterium grow at thefuel-water interface and can cause corro-sion as well as foul the fuel filter (17).

Sugars with the proper disposition ofhydroxyl groups also form ester complexeswith boric acid. A striking example is thesugar diacid disodium saccharate (glu-carate) which forms a 2:1 sugar acid:boratecomplex in aqueous solution that has theability to complex calcium ions. The two

ductor dopants, and a multitude of othersmall uses comprise 21% of the utilizationof B203 in the United States.

ChemistryThe aqueous chemistry of the borates isdependent on concentration and pH.Dilute aqueous boric acid solutions arecomprised solely of B(OH)3 and B(OH)4-species. Rapid exchange on the nuclearmagnetic resonance (NMR) time scaleresults in a single peak in the boron- 11NMR spectrum which moves steadily up asthe pH is increased. Concentrated solu-

Environmental Health Perspectives8

INTRODUCTION TO BORON: HISTORY, SOURCES, USES, AND CHEMISTRY

His-57

H

Figure 5. Boromycin (20).

diastereomeric forms of this complex areshown in Figure 4. Proton and carbon-13NMR spectra showed that the 3,4-diolportion of the tetrol fragment was involvedin coordinating with the boron atom (18).These complexes are of interest asbiodegradable builders to replace phos-phate in detergents (19).

A small group of boron-containingantibiotics contain a single tetrahedral boronatom in the center of the structure, com-plexed with two vicinal diol groups. Thefirst to be isolated and identified wasboromycin (20) (Figure 5) from Strepto-myces antibioticus. The related aplas-momycin was obtained from S. griseus(21); both show antibiotic activity againstgram-positive bacteria and represent theonly isolated natural products containingboron.

Bis(salicylato)borate salts (Structure 3)are readily formed in aqueous solutionfrom salicylic acid solution and boricacid (22). ,

Structure 3

2-Aminoalkanols form borate esters readilybecause of the added stabilization of theN-B dative bond. A striking example is theformation of triethanolamine borate(Structure 4) from a 1:1 aqueous solutionof boric acid and triethanolamine (16).

Boron in plant roots is believed to bereversibly bound as polysaccharide-boratecomplexes (2).

Figure 6. Borate intermediate in serine hydrolase inhibition.(32)

CONH2

tll~

Adenosine<®-®. 0 -

Figure 7. Borate inhibition of hydrogenase coenzyme by fibityl group complexing (31).

A recent mechanistic study of boricacid complexation with 4-isopropyl-tropolone and with chromotropic acid, a1,8-dihydroxynaphthalene derivative, hasshown that the rate-determining step is thechange in boron coordination from trigo-nal to tetrahedral (23).

0

B

Structure 4

Tetrahedral borate or boronate com-plexes have been shown to be involved inenzyme inhibition. Serine proteases wereproposed in early Russian work to be inhib-

ited by boric acid (24), and simple borateshave been patented as protease stabilizers inliquid detergent formulations (9,10).

Reactions such as acylation and deacy-lation are catalyzed by enzymes throughlowering of the energy of activation.Binding and stabilization of the near tetra-hedral oxyanion transition state by theactive site of the enzyme is how this isaccomplished. Thus, a transition state ana-log inhibitor is a species which binds theactive site in a way similar to that of thesubstrate. Serine hydrolase enzymes reactwith various borates, boronates, and bori-nates by forming a tetrahedral complexbetween the serine hydroxyl group and theboron atom. Hydrogen bonding to theimidazole ring of an adjacent histidine addsfurther stabilization.

X-ray structures have been worked outfor the benzeneboronic and 2-phenyl-

Volume 102, Supplement 7, November 1994 9

W G. WOODS

ethaneboronic acid (PEBA) complexes ofsubtilisin BPN'(Novo) (25) and for thePEBA complex of a-chymotrypsin(a-CHT) dimer (26). Further stabilizationof the hydroxyls on boron is gained byhydrogen bonding to other amido groupslining the oxyanion hole (Figure 6).

Subtilisin Carlsberg (27) and choles-terol esterase (28,29) also are inhibited by arange of aliphatic and aromatic boronicacids. Work on inhibiting a-CHT and cellreplication with a variety of boronic acidsconcluded that the a-CHT activity wasassociated with chromatin in normal andtumorous tissue of mice (30). It has beendemonstrated that certain boronic acidsinhibit protease activity in rat liver chro-

matin (31). It was concluded that goodboronate inhibitors of CHT, like PEBA,inhibit cell replication and that this effect isexpected to be higher in rapidly proliferat-ing cancer cells than in normal tissue (30).

Complexing of the ribose group ofnicotinamide adenine dinucleotide (NAD)is preferred electrostatically over that ofreduced nicotinamide adenine dinucleotide(NADH), leading to inhibition of thiscoenzyme system (Figure 7) (32). Theeffects of boron compounds on enzymecatalyzed reactions have been thoroughlyreviewed through 1979 by Kliegel (33).

ConclusionsBoron is present in every part of the

environment and it is likely that lifeevolved in the presence of the element.Boron is essential to plant life, but canbe herbicidal at high levels. Borates haveeffects on a variety of bacteria, fungi,and insects. Boron in biological systemscan be expected to be associated withone or more OH groups.

Borates are used widely in industrialand domestic applications. Boron hasbeen shown to influence a variety ofenzymes, involving both stimulation andinhibition. Enzyme interactions proba-bly represent the most important featureof boron chemistry from the point ofview of the health effects considered inthe following papers.

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INTRODUCTION TO BORON: HISTORY, SOURCES, USES, AND CHEMISTRY

cell replication. Biochem Pharmacol 35:3587-3591 (1986).31. Carter DB, Ross DA, Ishaq KS, Suarez GM, Chae C-B. The inhi-

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