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Mineral Properties and Their Contributionsto Particle
ToxicityGeorge D. Guthrie Jr.Geology and Geochemistry Group, Los
Alamos National Laboratory, LosAlamos, New Mexico
It has been recognized since at least as early as the mid-1500s
that inhaled minerals (i.e.,inorganic particles) can pose a risk.
Extensive research has focused on the biological
mechanismsresponsible for asbestos- and silica-induced diseases,
but much less attention has been paid tothe mineralogical
properties and geochemical mechanisms that might influence a
mineral'sbiological activity. Several important mineralogical
characteristics control a mineral's reactivity ingeochemical
reactions and are likely to determine its biological reactivity. In
addition to thetraditionally considered variables of particle size
and shape, mineralogical characteristics such asdissolution
behavior, ion exchange, sorptive properties, and the nature of the
mineral surface(e.g., surface reactivity) play important roles in
determining the toxicity and carcinogenicity of aparticle.
Ultimately, a mineral's species (which provides direct information
on a mineral's structureand composition) is probably one of the
most significant yet most neglected factors that must beconsidered
in studies of toxicity and carcinogenicity. Environ Health Perspect
105(Suppl 5):1003-1011 (1997)
Key words: particles, minerals, toxicity, carcinogenicity,
mechanisms
Introduction
In his 1556 treatise De Re Metallica,Georgius Agricola noted
that minersexposed to dust from some mines hadincreased risks for
various diseases, includ-ing consumption (1). Although it is
notclear from Agricola's description whetheror not consumption
refers specifically totuberculosis or more generally to
pneumo-coniosis, it is interesting to note that thelinks both
between dust exposure andtuberculosis and between dust exposureand
pneumoconiosis were borne out inlater studies, induding work 400
years laterby King and co-workers (2-8). By the timeof King and
co-workers, it was generally
This paper is based on a presentation at The SixthInternational
Meeting on the Toxicology of Naturaland Man-Made Fibrous and
Non-Fibrous Particlesheld 15-18 September 1996 in Lake Placid,
NewYork. Manuscript received at EHP 26 March 1997;accepted 20 May
1997.
thank Eugene llton for permission to use Figure4; Art Langer for
reminding me of Nagelschmidt'sbackground as a clay mineralogist;
and Bill Carey andtwo anonymous reviewers for critical reviews of
themanuscript. This work was supported by theDepartment of Energy
through contract W-7405-ENG-36 to Los Alamos National
Laboratory.
Address correspondence to Dr. G. Guthrie, 1187Rood Hall, Dept.
of Geology, Western MichiganUniversity, Kalamazoo, Ml 49008.
Telephone:(616) 387-5343. Fax: (616) 387-5513.
E-mail:[email protected]
recognized that inhaled minerals can initiatea number of
responses, including theformation of ferruginous bodies
(9-12),fibrosis (3,4,6-8,13-17), and shortlythereafter
carcinogenesis (18-21).
Even (perhaps especially) at these earlystages of research on
mineral-inducedpathogenesis, it was recognized that the keyto
understanding why some minerals aretoxic or carcinogenic is to link
mineralogicalproperties with biological processes. Muchof this
insight came from the work by Kingand co-workers, through their
collabora-tions with G. Nagelschmidt, a mineralogist,and to a
lesser extent V.M. Goldschmidt,who is considered by many to be
thefounder of modern geochemistry. Throughthese collaborations,
King and co-workersinvestigated the biological activity of a list
ofminerals that is truly impressive: olivine(22), kaolin minerals
(4,6,14), micas (2),various silica polymorphs (induding
quartz,tridymite, cristobalite, and amorphoussilica) (5,7,23-25),
various forms of alu-minum and iron oxides and hydroxides(including
boehmite or y-AIOOH, corun-dum, or a-AI203-which is
isostructuralwith hematite, y-A1203, goethite, ora-FeOOH, and
lepidocrocite ory-FeOOH)(3,8), and berlinite or AIPO4 (8).
As demonstrated by their use ofmineral species names to describe
their
materials, King and co-workers must haverecognized that the
structure and composi-tion of a material (the two
characteristicsthat define a mineral species*) are criticalto
determining the way in which a materialinteracts with its
environment. This is afundamental principle in the
geosciences,where it has long been recognized that eachmineral
species possesses unique properties(derived from its crystal
structure and/orcomposition) and that these propertiesdetermine how
a mineral interacts withits environment.
In this paper, I address a number ofmineralogical properties
that affect how amineral interacts with its environment.Some of
these properties have been shownto affect toxicity and
carcinogenicity, andsome are known to be important in geolog-ical
processes but have not been exploredwith respect to biological
processes. Anunderlying principle throughout this paperis that
pathogenesis originates at the min-eral-fluid-cell interface, so
interactionsbetween a mineral and fluid or a mineraland a cell may
ultimately lead to disease.These interactions range from
indirectinteractions between a mineral surface andextracellular or
intracellular fluids (includ-ing fluids associated with
phagosomesand/or lysosomes) to direct interactionsbetween a mineral
surf&ce and cell-surfacereceptors or other components of a
cell'smembrane. To gain insight into what min-eralogical properties
are important for amineral's role, we can borrow from
thegeosciences where a large range of min-eral-fluid interactions
have been and con-tinue to be studied. I discuss briefly
severalproperties that are commonly addressed-particle size/shape,
mineral species (struc-ture/composition), dissolution, and
surfaces.I also discuss two properties that are
seldomaddressed-cation exchange and oxida-tion/reduction. All these
properties areknown to affect the way in which a min-eral interacts
with a geological fluid andare likely to play roles in
mineral-fluidinteractions in the lung.
*Mineral species are applied in much the same wayas animal/plant
species: A mineral species is themost specific distinct division
within the classificationscheme for minerals. It defines a specific
crystalstructure and a composition or compositional range.Sometimes
subspecies (termed varieties) are definedbased on characterstics
such as morphology or crys-tal habit (e.g., crocidolite is the
varietal term forasbestiform riebeckite).
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Mineralogical PropertiesImportant in ToxicitySolids can be
divided into two broadcategories based on the property of
transla-tional periodicity: crystalline and noncrys-talline (or
amorphous). Translationalperiodicity is the characteristic that
allowsthe extended structure existing throughouta single-phase
particle to be represented bya smaller subunit that is translated
alongnon-coplanar vectors in three dimensions,in the same way that
a wall might be repre-sented by a brick or cinderblock that
istranslated in two dimensions. Translationalperiodicity is
necessary for a structure todiffract X-rays constructively (which
is whyproteins must be crystallized for structuralanalysis), but it
also imparts a wide rangeof properties to minerals that
differentiatethem from amorphous materials. In fact,crystallinity
appears to be an importantfactor in toxicity/carcinogenicity, as
exem-plified by the higher biological reactivity ofsome types of
crystalline silica comparedwith noncrystalline silica (26).
Much of our insight into how a mineralinteracts with a fluid
comes from observa-tions on geological systems. Reactionsinvolving
minerals in geological environ-ments are often mediated by fluids;
conse-quently, mineral-fluid interactions areamong the most widely
studied phenom-ena in mineralogy, geochemistry, and otherbranches
of the geosciences. Our currentunderstanding of these phenomena has
ledto several important geological tenets thatare equally important
in mineral toxicity/carcinogenicity:* a mineral affects its
environment;* a mineral is affected by its environment;* mineral
species is a critical descriptor of
a material's overall characteristics;* the properties of a
mineral species can
vary between samples.Although these tenets may appear self-
evident (as they undoubtedly did to King,Nagelschmidt,
Goldschmidt, and their co-workers), they serve as important
remindersthat mineralogy is an integral component ofmineral
toxicity. As such, care must betaken to ensure that mineralogical
issues ina study are as adequately addressed as bio-logical issues.
However, it also means thatthe mineralogical approaches to
toxicitystudies can provide important new insightsinto the
molecular processes that occur. Forexample, the first tenet
embodies thenotion that a mineral can induce reactionsin a cell or
physiological fluid. Hence, byappropriate manipulations of
mineralogical
variables, one can alter a biological responsein a systematic
way to reveal the mineralog-ical and biological molecular
mechanisms(in much the same way that one manipu-lates the
biological variables to reveal mech-anisms). The second tenet
embodies thenotion that the way a mineral is changed bya reaction
preserves information about thereaction. Hence, one can learn
somethingabout a mineral-fluid-cell interaction byobserving not
only how the cell and fluidrespond but also by observing how
themineral responds.
These principles form the motivationfor the remainder of this
paper, which willattempt both to address some of the miner-alogical
properties important in toxicityand to illustrate how a combined
miner-alogical and biological approach canimprove our understanding
of these com-plex processes. The first three topics (min-eral
species, particle size and shape, andsample history) cover
properties that ingeneral should be determined for everysample
studied. The remaining four topics(ion exchange,
oxidation/reduction, disso-lution, and surfaces) are additional
miner-alogical factors that are key components ofa mechanistic
model for mineral-inducedpathogenesis. I focus primarily on the
firsttwo topics because the last two topics arecovered extensively
elsewhere (includingother articles in this volume that
addresspartide surfaces).
Mineral Speces: Structureand CompositionA determination of the
mineral speciesused in a specific study is the bare mini-mum
required in terms of sample charac-terization. Although mineral
species oftentakes a back seat to particle size and shape(discussed
below) in most studies on toxic-ity and carcinogenicity, it is, in
fact, one ofthe most critical characteristics because itprovides
information on the bulk structureand composition of a material-the
twomost basic characteristics of a material thatultimately have a
profound effect on manyof the other mineralogical
propertiesimportant in pathogenesis.
Both the structure and composition areneeded to define a mineral
species becauseneither alone is sufficient to describe
theproperties of a material; this is well illus-trated by the
minerals quartz, stishovite, andrutile. Figure 1 shows polyhedral
representa-tions * for the structures of these materials.Quartz and
stishovite are compositionallyidentical (SiO2) but have markedly
differentstructures (Figure 1A-D). This structural
difference imparts different solubilities(important in
biodurability and possibly tox-icity), different functional groups
on the sur-face (related to different bonding strengthsfor various
surface oxygen sites, which trans-lates, for example, into
different dissociationconstants for protons on the surface),
anddifferent tolerances for various trace elemen-tal contaminants
(to name a few differencesimportant in toxicity). Stishovite and
rutileare structurally identical (Figure 1B,D) buthave different
compositions (SiO2 andTiO2, respectively). This compositional
dif-ference affects solubilities, surface functionalgroups, and
bulk oxidation-reduction char-acteristics, to name a few.
(Interestingly, sti-shovite and rutile are both nonfibrogenicand
noncarcinogenic, suggesting that thisstructure type may not elicit
a pathogenicresponse. Although this observation has beenalluded to
often, no one has tested thismechanistic hypothesis by
investigating sys-tematically the many other materials withthis
structure such as pyrolusite or MnO2,cassiterite or SnO2, argutite
or GeO2, andmarcasite or FeS2.)
The asbestos literature has evolved to thepoint where the use of
terms like crocidolite(the asbestiform variety of the
mineralspecies riebeckite), amosite (a commercialterm mostly
referring to the asbestiformvariety of the mineral series
cumming-tonite-grunerite), asbestiform tremolite, andchrysotile is
commonplace. Similarly,studies on the oxides of silicon
(typicallySiO2 or silica) often use proper mineralspecies terms,
like quartz, tridymite, andcristobalite. Nevertheless, since the
days ofKing and co-workers (who were faithful tothe use of mineral
species names for silicapolymorphs as well as for a vast array
ofother minerals in their studies), the use ofterminology has
become much less rigorous.Now the use of the nondescript term
silica isnot uncommon and the use of chemicalterms (and not
mineralogical terms) forother materials is the norm-e.g., studies
onthe oxides of titanium almost always use
*Most rock-forming minerals (i.e., minerals that arecommon in
rocks found at Earth's surface) arelargely composed of oxygen
coordinating cations in asmall set of regular shapes (termed
polyhedra).Hence, portions of mineral structures are
commonlysimplified by replacing some of the atoms with poly-hedra
(26-28) for discussions on the graphical repre-sentations of
mineral structures), an approachpioneered by Linus Pauling (29),
who began his sci-entific career as a mineralogist. More detailed
pre-sentations of minerals and their structures can befound in a
general mineralogy text such as theManual of Mineralogy (30).
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MINERALOGICAL PROPERTIES AND PARTICLE TOXICITY
B
D
Figure 1. (A) Polyhedral representation of the left-handed
quartz structure (94) projected nearly down the c-axis.Each
tetrahedron consists of Si4+ at the center and 02- at each of the
four apices. (B) An isolated double helix fromthe quartz structure.
(C,D) Polyhedral representation of the stishovite and rutile
structure (95) viewed down the b-axis. Each octahedron consists of
a metal ion (Si4+ for stishovite and Ti4+ for rutile) at the center
and 02- at eachof the six apices.
the term titanium dioxide to describe amaterial. This lax
approach to sampledescription can lead to a false sense of
con-fidence in the ability to interpret resultsfrom various
studies. For example, one isled to believe that the results for
titaniumdioxide in one study can be compared withresults for
titanium dioxide in anotherstudy. In fact, TiO2 or titania
crystallizes inat least seven different polymorphs (i.e.,different
structures), including rutile(Figure 1C,D), anatase, brookite,
andTiO2 (B) (31) for figures of these last threepolymorphs). In
addition, titanium oxideswith stoichiometries different from
TiO2occur (i.e., where the oxidation state of Tiis not uniformly
Ti4+). Each of these formsof titanium oxide has different
properties(31). For example, anatase is used as a cat-alyst (32,33)
and photocatalytic (34-36).Differences in biological activities
have alsobeen noted for the polymorphs of TiO2(37-39).
Nevertheless, it is commonplaceto read that a particular study used
TiO2 asa negative control. Clearly, in the absenceof information on
the crystal structure of a
material, the use of a chemical term such astitania or titanium
dioxide is inadequateinformation to provide for a sample usedin a
toxicity study.
Although mineral species is one of themost critical
characteristics to be deter-mined for a sample used in a toxicity,
thereare cases for which the use of a mineralspecies name (which
defines the ideal com-position and bulk structure) is
insufficientinformation for describing a sample. Withrespect to
composition, this can occurwhen the mineral species is defined for
arange in composition or when the compo-sition of the sample
deviates from the idealstoichiometry. The first case is well
illus-trated by the asbestiform amphiboles. Forexample, asbestiform
riebeckite (or croci-dolite) has an ideal end-member composi-tion
of Na2Fe3+Fe2+ Si8O22(OH)2, but themineral species riebeckite is
actuallydefined over a much broader range of com-position, which
allows for a) potassiumand sodium to partially occupy the "A"site,
which is omitted in the ideal formula;b) up to 50% replacement of
the iron by
magnesium; and c) limited other substitu-tions for sodium, iron,
silicon, andhydroxyl (40). These compositional varia-tions can have
profound affects on thesample's properties, including toxicity.
Forexample, one can easily imagine that a sig-nificant replacement
of iron by magnesiumwould have an impact on the particle'sability
to drive the Fenton-type reactionsthat are currently believed to
explain croci-dolite's extreme biological activity (41,42).Hence, a
compositional analysis must beprovided for the particular
crocidolite sam-ple used in a toxicity study. The secondcase can
occur even for well behaved min-erals like quartz, which can have
up to afew wt-% of elements like Al and Fe (28).These minor and
trace elements can have asignificant impact on the biological
reactivityof quartz (43).
In some cases, mineral speciesinadequately describes a
material's struc-ture because the presence of defects (whichare
deviations from the ideal structure)introduce significant variation
into thematerial's properties. For example, ostensi-bly non
asbestiform riebeckite and asbesti-form riebeckite (crocidolite)
share the samestructure. However, samples of crocidolitegenerally
have a large proportion of chain-width defects, which imparts
uniquemechanical properties on crocidolite (i.e.,crocidolite is
flexible whereas nonasbesti-form riebeckite is not) (27). These
defectscan additionally impart other differences inthe properties
between the two materials(e.g., the diffusion of cations within
andthe dissolution properties of amphibole areaffected by
chain-width defects, both ofwhich will affect the release of iron
to thefluid). Hence, the differences in biologicalactivities noted
for these materials (44,45)cannot be uniquely attributed to
particlemorphology, as is often done.
Partide Size and ShapeParticle size and shape are
universallyconsidered important factors in pathogene-sis and are
faithfully reported in moststudies. There are several understood
(orpartially understood) mechanisms bywhich size and shape may
influence toxic-ity and carcinogenicity, including fate ofthe
particle (from deposition to physicaltranslocation to cell-mediated
transloca-tion), surface area, types of reactive
sites,particle-cell interactions, and catalysis.
Particle size and shape exert a majorcontrol on deposition,
translocation, andclearance (i.e., the fate of a particle
followinginhalation). Deposition is affected by a
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combination of physical limitationsimposed by the constricting
airways-which reduce to approximately 50 pm bythe time they reach
the alveolar ducts(46)-and aerodynamic and
gravitationalfactors-which control processes such asimpaction,
settling, interception, and diffu-sion (47). These processes lead
to heteroge-neous particle-size deposition throughoutthe conducting
airways and lungs. Forexample, larger particles (>0.2 pm)
aredominantly deposited in the nasopharyn-geal region (47), whereas
smaller particlesare deposited in the respiratory tract.
Thistranslates into approximately 10 pm as aneffective maximum size
for respirable parti-cles in humans and approximately 5 pm asan
effective maximum size for respirableparticles in rats (48).
Translocation (partic-ularly from the airways through theparenchyma
to the pleura) is also affectedby particle size and shape as
demonstratedby the observation that fibrous particles arecommonly
found in the pleural space.Finally, clearance mechanisms-e.g.,
disso-lution rate, which is an important clearancemechanism for
rapidly dissolving materialslike chrysotile (49), and cellular
clearancemechanisms such as phagocytosis andtranslocation-are
strongly limited byparticle size and shape.
Size and shape also determine thesurface area of a particle and,
perhaps moreimportantly, the surface area per unit vol-ume or per
unit mass of the sample. Particlevolume (and hence mass) scales
with thecube of a particle size, whereas the surfacearea of a
smooth particle scales with thesquare of particle size. In other
words, smallparticles have larger surface areas per unitmass than
larger particles, which means thatsmaller particles have more
reactive surfaceavailable on a per-mass basis. Consequently,a
number of researchers have argued infavor of comparing toxicity of
materials ona per-fiber (or per-particle) basis rather thanon a
per-mass basis (50). "Per surface area"is probably a more
defensible basis onwhich to compare results, but only a fewstudies
have endorsed this approach (51).
Another important aspect of particlemorphology relates to the
nature of reactivesites on the particle surface (as
discussedbelow), because a particle's morphologydetermines the
exposure of various reactivesites. For example, the active sites
associ-ated with the ends of crocidolite fibers(which differ
dramatically from the activesites associated with the sides of the
fibers)have lower exposed areas than they wouldin a case where the
crocidolite formed
Figure 2. Schematic representation of a particle with afibrous
versus platy morphology. If the fiber were a cro-cidolite fiber 0.1
pm x 0.1 pm x 0.1 pm (i.e., 0.1 pm3),the fiber ends-the shaded end
that correspondsapproximately to the (001) plane-would have a
sur-face area of 2 x 0.01 pm2; whereas a hypotheticalplaty
crocidolite of the same volume (1 pm x 1 pm x0.1 pm) and with the
plates parallel to (001) wouldhave a (001) surface area (shaded) of
2 x 1 pm2, i.e.,two orders of magnitude greater. Hence, particle
mor-phology impacts the exposed surface areas of a material.
sheet-like particles normal to the fibers(Figure 2).
Recent work presented at this confer-ence suggests that fiber
length may affectparticle-cell interactions by causingmechanical
stresses on the cell surface (52).Mijailovich and co-workers
hypothesizethat the contact of a long fiber with alveo-lar
epithelium that is in cyclic motionbecause of tidal breathing
causes stresses onthe cell that trigger a response.
Finally, a number of materials becomeeffective catalysts when
their particle sizebecomes extremely small (i.e.,
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MINERALOGICAL PROPERTIES AND PARTICLE TOXICITY
in the colony-forming efficiency of ratlung epithelial cells
exposed to a suite ofcation-exchanged erionites (Na, K, Ca,
andFe3+) all derived from the same parentmaterial. However, using
the same suite oferionite samples, we have found that
cationexchange may have an effect on cytotoxic-ity, gene response
(as measured by steady-state levels of mRNA for c-jun),
andapoptosis in some rat pleural mesothelialcells (Guthrie G,
Timblin C, Mossman BT,unpublished data). For example, prelimi-nary
results suggest that Na- and K-exchanged erionite may be more
cytotoxicat 72 hr than Ca- and Fe-exchanged erion-ite (Figure 3).
Initially, one might condudethat cation exchange, which happens
rapidlyin simple aqueous solutions, would only besignificant
immediately after exposure.
A
- - - - 8-hr exposure72-hr exposure
B
co
0.8 -
0.6 -
Dose, jg/cm2
Figure 3. Effect of cation exchange on (A) Na-exchanged
erionite; (B) Ca-exchanged erionite] erionitecytotoxicity on rat
pleural mesothelial cells (Guthrie,unpublished data). Erionite from
Eastgate Nevada wascation exchanged in chloride solutions and
washedthoroughly to remove remaining salt. Details of
theexperiments are in Timblin et al. (unpublished data).
However, the kinetics of cation exchangein a complex biological
fluid which con-tains molecules that could inhibit exchangeby
interfering with ion channels on themineral surface are not
known.
CatalysisMinerals-particularly but not exclusivelyzeolites and
some clays-are exploited exten-sively as catalysts. The mechanisms
by whichminerals function as catalysts generally relateto their
ability to donate or accept electronsor protons, to provide a
stabilizing surface(a template) for reacting components, andto
exclude molecules of a specific shape orsize from the catalytic
sites. In other words,minerals can function in a manner similarto
that of traditional enzymes.
The proton and electron donor/acceptorsites (the acid/base
sites) of the mineral arecommonly exploited and are responsible
forthe widespread use of zeolites as catalysts inthe cracking of
hydrocarbons. The acid/base characteristics of framework
silicatessuch as zeolites are strongly influenced bythe
substitution of aluminum for silicon inthe tetrahedral framework.
This substitu-tion can be charge compensated for in anumber of
ways, including the associationof a proton with the underbonded
oxygensaround the aluminum. Hence, these sites(like many other
surface sites on minerals)function in a manner similar to that
ofenzymes in that they can alter the apparentlocal activity (or
thermodynamic concentra-tion) of a species like hydrogen at a
specificreactive site. A number of different suchsites can exist on
the surface of zeolite, andrange from silanol groups (Si-O-H) to
thealuminum equivalent (Al-O-H) to protonsgenerally associated with
an aluminum-exchanged tetrahedral site, e.g.,
H
AI-O-Si
The protons associated with each of thesesites have different pK
values. There recentlyhas been much success in applying ab
initiocalculation methods to calculate the reactiv-ity associated
with such surface sites (72).
It has long been argued that hydro-genated surface sites (e.g.,
silanol groups)are responsible for the toxicities of the sil-ica
polymorphs because they function ashydrogen donors. In support of
this is thefact that the hemolytic reactivity of quartzcan be
diminished (73) by treatment withpolyvinyl-pyridine-N-oxide
(PVPNO), apolymer that binds to proton donor sites.
Oxidation-ReductionThe transfer of electrons between a
mineraland fluid drives a number of geochemicalprocesses. In
general, silicates and manyother minerals are considered to be
insula-tors (i.e., they do not conduct electronsrapidly). At higher
temperatures (hundredsof degrees Celsius), some silicates begin
toconduct electrons sufficiently rapidly toallow their electrical
properties to be stud-ied somewhat routinely. The
oxidation/reduction properties of the amphiboleasbestos minerals
crocidolite and amositehave been studied extensively at high
tem-peratures, beginning with the pioneeringstudies ofAddison and
co-workers (74-76).Although they focused on higher tempera-tures
(450-6150C), they studied the kinet-ics of the reaction down to
350°C andnoted that oxidation can occur even at0°C. At lower,
physiological temperatures,the rates may be too low to measure
effec-tively in a laboratory experiment, but theymay be
sufficiently high to provide achronic source (or sink) of electrons
forreduction (or oxidation) of fluid species(e.g., to form free
radicals).
Interestingly-and predictably based onmineralogy-the resistance
of amphibolesvaries strongly with crystallographic direc-tion.
Electron conduction occurs mostrapidly along the length of the
fibers (i.e.,along the octahedral strips that containiron).
Crystallographically similar electronconduction pathways occur
within the octa-hedral sheets of phyllosilicates like biotite(i.e.,
at the edges of the sheets readilyformed by the dominant cleavage
directionin micas), which is why micas are effectiveinsulators
normal to their sheets (they areexploited this way in capacitors)
but havemuch lower resistance along their sheets.
Although most investigations of oxida-tion-reduction and
conduction in silicateshave focused on high temperatures,
theseprocesses are known to be important for anumber of reactions
at lower temperatures(e.g., < 50°C). For example, electron
transferreactions have been shown to be importantin the weathering
at ambient temperaturesof minerals such as amphibole (77)
andmagnetite (78), in the formation of copperore deposits (79), and
in the sorption ofmetals such as Cr to the mineral surface at250C
(80). Clearly, the transfer of elec-trons between minerals and
fluids is impor-tant at physiological temperatures and, asshown in
Figure 4, this redox process isstrongly controlled by the crystal
structure.
The propensity for a redox reaction tooccur can be assessed by
comparing the EH
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Figure 4. A secondary electron image of a biotite crystal that
has interacted with a fluid containing silver sulfatesuch that
electrons have been transferred from the mineral to the Ag+ in the
solution. Crystals formed at 25°C overthe course of several days.
Note that the silver crystals form at the edge of the biotite
crystals where the octahe-dral sheets surface. Photograph used with
permission of Eugene Ilton (Lehigh University).
or pe values for the individual half reactions,which ultimately
relate to the electrochemi-cal potentials (EO) for the half
reactions.Electrochemical potentials for aqueous reac-tions can be
readily determined and havebeen tabulated for a number of half
reac-tions. For example, [Fe3+]aq + e -* [Fe2+]aqhas an E° of 0.77
V (81). Unfortunately,the electrochemical potential for
variousredox reactions in minerals are poorlyknown. White and Yee
(77) bracketed theelectrochemical potential for Fe3+o-Fe2+ ina
hornblende amphibole at between 0.33and 0.52 V under their
experimental con-ditions. White and co-workers (78) deter-mined the
electrochemical potential forFe3+o-Fe2+ in a magnetite sample
(-0.27 Vat pH 7) directly by measuring the self-induced potential
of a magnetite electrode(a procedure that requires a large
singlecrystal). Ilton [(79,82); personal communi-cation] has found
that the electrochemicalpotential for Fe3+->Fe2+ in biotite is
proba-bly close to the values determined byWhite and Yee for
hornblende, based onthe observation that Ag+ reduces vigorously(E =
0.80 V; even at a concentration of 10ppm), whereas Cu2+ (EO = 0.34
V) reducesbut much less vigorously.
The mechanisms by which a mineralcan transfer electrons from
within the crys-tal to the surface also must be known toevaluate
mineral-catalyzed redox reactionsin a fluid. An important component
of themineral-catalyzed redox is that the crystalmust remain charge
balanced (or at least
close to neutral charge). Hence, for theoxidation of
crystal-bound iron to reduce asolution-bound species, the reaction
can bebroken down into several steps:
(Fe2+)crystal -e (Fe3+)crystal + (e)surface [1]
(OH-)crystal -e (02-)crystal + (H+)surface [2a]
(R+)crystal -e (R+)surface [2b]
(02-)surface + ELcrystal -* (02-)crystal [2c]
where O designates a vacancy or unoccu-pied crystallographic
site and R+ designatesa cation site. The reactions are written
withrespect to changes within the mineral andwhere the surface
represents the interfacebetween the mineral and the fluid (e.g.,
anelectron at the surface can transfer to thefluid). The
electron-exchange reaction(Equation 1) is written involving
iron,because this is the most common polyva-lent cation in
minerals. Equation 2 sum-marizes three possible mechanisms
formaintaining charge balance within thecrystal (74). Equations 2a
and 2b maintaincharge balance by diffusing a chargedspecies out of
the crystal. Hydrogen,because of its small size, would be the
easi-est of the possible cations to diffuse out ofminerals such as
amphiboles and, in fact,
Addison and co-workers (74) proposed thismechanism for
crocidolite oxidized at 450to 615°C. Scott and Amonette
(83)endorsed a slightly different mechanism inweathering conditions
(i.e., low tempera-tures) whereby charge balance is maintainedby
dissolution of iron after oxidation(Equation 2b). In some materials
(e.g.,magnetite or Fe3O4) diffusion of hydrogenis not an option, so
mineralogical changesoccur. For magnetite, oxidation occursthrough
the formation of maghemite (78).The mechanism by which a material
oxi-dizes has a profound effect on the rate ofoxidation (i.e., on
the rate of sustainedelectron transfer).
How, then, might electron transferprocesses play a role in
pathogenesis?Electron transfer involving the surfaceof minerals has
been attributed to theincreased biological activity and
heightenedformation of free radicals associated withfreshly
fractured quartz compared to agedquartz (54,84,85). Such a process
producesa transient or acute burst in free radicalsthat ceases once
the particle surface hasbeen passivated (i.e., once the surface
radi-cals have equilibrated). Electron transferinvolving the
internal regions of the crystal(through transfer between the
surface andinterior) has the potential to produce a sus-tained or
chronic redox condition to driveformation of radicals in the fluid.
In addi-tion, once electron transfer to the fluid hasoccurred, iron
release to the fluid (to main-tain charge balance) could provide
anothermechanism for driving Fenton-type reac-tions. Several lines
of evidence support thenotion that electron transfer processes
areimportant in pathogenesis. Fubini and co-workers (86) reported
that magnetite willbreakdown hydrogen peroxide, whereashemnatite
(Fe2O3) will not, which suggeststhat Equation 1 plays an important
role inthe formation of free radicals. Figure 4shows a mica crystal
that has reduced sil-ver from solution to cause its precipitationat
the redox-active edges. Similarly, in hisdescriptions of
ferruginous bodies, Roggli(87) shows several particles of mica
recov-ered from human lung (his Figures 3-18);the particles have
become coated with aferruginous material only at the redox-active
edges of the crystals. Although themechanism of ferruginous body
formationis still not understood in its entirety, it isbelieved to
relate to the breakdown of aniron protein such as ferritin (which
can bedenatured by a redox mechanism). It isinteresting to note
that asbestos bodiestypically have more precipitate at their
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September 19971 008
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MINERALOGICAL PROPERTIES AND PARTICLE TOXICllY
ends, which are crystallographicallysimilar to the edges of mica
and which areknown to be the redox-active areas athigher
temperatures.
Dissolution BehaviorDissolution can be a significant componentof
particle clearance mechanisms and cancause the release to the lung
fluid of ionssuch as iron, other metals, or other toxicelements.
Dissolution is often used as abasis for differentiating
nonhazardous frompotentially hazardous minerals, where
non-hazardous minerals have a low biodurabil-ity and, hence, do not
remain in the lungfor long periods of time.
Unfortunately, there are few data onthe kinetics of mineral
dissolution in bio-logical fluids that are also based on
mecha-nistic dissolution models for minerals. Onesuch study was
recently conducted byHume and Rimstidt (49), who based theirmodel
on the release of silica as the rate-limiting step for chrysotile
dissolution.Their dissolution rate model predicts that
chrysotile fibers will dissolve completely indays to months
under lunglike conditions.
It has long been recognized that mineralburdens in human lungs
are not exactly rep-resentative of the dusts to which an
individ-ual is exposed [reviewed by Churg (88)].For example,
chrysotile miners typicallyhave a nearly steady-state level of
chrysotilein their lungs but a continuously increasinglevel of
tremolite (a minor contaminant ofthe chrysotile ore). These
observations areconsistent with the rate model of Humeand Rimstidt,
in that the steady-state levelsobserved represent competition
betweendeposition and dissolution. Dissolution ofminerals under
these conditions is discussedin detail by Hochella (89).
SurfacUltimately, the surface is that part of amineral that
interacts with a fluid or cell.For some materials, the structure at
thesurface can differ substantially from thestructure exhibited by
the bulk (89). Thesedifferences between the surface and the
bulk can range from simple distortionalrelaxation of surface
atoms to a completelydifferent material on the surface.
Frequently,a dissolving mineral will form a precipitateat the
surface with a composition/structurethat differs from the bulk
material. Evenchemically simple minerals such as quartzcan have
surfaces that are structurally dif-ferent from the bulk (90,91); at
anotherextreme would be a fiber of amphiboleasbestos, which likely
has much of its sur-face covered by a phyllosilicate-like
materialthat is both compositionally and structurallydistinct from
the bulk amphibole (27).Clearly, there is a large range of
surface-related factors that can change the activesites on the
surface, can affect binding/sorp-tion processes on the surface, can
affect dis-solution characteristics, and can generallyhave an
impact on a mineral's pathogenicpotential. A detailed discussion of
surfacecharacteristics important in pathogenesis isbeyond the scope
of this paper, but someof these aspects are addressed in
Guthrie(26,28) and Hochella (89).
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