In rorm:ation Circular 8639

Proceedings of tIle SYlnposiui:n on Talc,"'lhSllington, D"C", IVlay 3, 19'j3

Compiled by"Aure) Goodwin, --

l'det.al. and Nonmetal I\1ine Health and Safety, Washingtqn, D.C.

UNITED STATES IlEP:\RT~,IEr"';T OF Tn E l~TEiUO!t

Hogt'rs C. B. Morton. Secretary

UlJl~EAtl or MINESThom;l~ V. f:dkie, Din'dcl"

4

tHE lUOLOGICAL ACTION OF TALC AND OTIIEP.. SILICATE NINERALS

by

Gerrit W. H. Schepers, l-f.D. D D.Sc.1

Introduction

the recenr revelation that prolonged human inhalation of cert~in fibrousminerals (for eYoample, crocidolite) mny be associated with· excess prev31~nce.

of malignant neoplasia of the lung, and even of Qther organs $uch as thest~mach or colon, has focussed attention on the biological potentials of allthe fibrous minernls. For reasons not quite clear to this nuthor, talc hassomehow and proba~y quite unjustifiably become embroiled in the issue of thecarcinogenicity of asbestiform minerals. "Talc, though a silicate, is by nomeans a fibrous mineral.

It is quite important, however, to thcr~ughlj review biological reactiv­ity to tales because their industrial uses are so diversified. Direct hUQanexposure is consider2ble, involving all elements of humanity, practically fro~

cradle to grave. There also is a contradiction betHeen the strin(;ent rulesfor dust suppression in mining or milling of talc and the almost total lack ofcontrols over talc when released for private use.

The crucial issue is whether all silicate minerals are equally p~thogenic

To resolve this question it is necessary to review what is on record concern­ing the biological action of talc and compare this with what is knmm about·the adverse properties of other silicates ~id especially th? asbestiforrnminerals.

The biological potentials of a variety of natural and synthetic silicateshave b~en personally r"esearched over the pas t J dec<ldes. TItese studies haveincluded investigation of human subjects, experimental animals, and a reviewof the literature •. Jltiman studies include observaticns on crocidolite andarnosi tc min~rs· and millers in Africa, chrysotile, tremolite, and duc miners,millers, and industrial workers in the United States and Canada, and textile'Workers in f iberg lass and synthetic fiber indus tri-es. The nu.'nber ci !H..:rn~nsubjects studied e:-:cecds 10,000. These stlldies are e\'alu<lted against a back­ground of famili3rit)' through personal clinical experience and res~arch cf thepathogenic action of a variety of other natural nnd synthetic siliceo'..!s, non­siliceous, and chemic"l aud synth"etic subs t<lnces. nl(:~ clinical subjec tsexceed JOO,OOO and necropsies have been per.formed on over 10,000 dece~~edindustri~l workers.

Animal studies l'n'/e recentl)' been reviet.:ed in a publication on Tu~lors ofPfinlntes ~nd Rodents (2). These included researches C'n the biological proper­ties of 1.07 industrially ir.lportant: OIaccri.o.ls through cxp~rirnental c::-:posures of7,906 Mil!lals.

!Chief~ j·it!dical Scn'it:e of Veter;t!:; Adntniscr<Jcitm. Lcb.:ll1on, Pac

so

The published literature is vast and ~ver increasing. In excess of 4 p OOOpapers have been reviewed. If' these do not include ~ll that has been writtenon this subject of pneumoconiosis p any omissions would be unintentional.

For practical purposes all references cannot be cited nor will it bereasonable in a paper of the intended scope of this presentation torecapitu­late all that is kno~~ about the biological actions of talc and fibrous envi­ronmental agents. It 'Will be feasible only to. summarize pertinent highlights.

Fibrous and Nonfibrous Dusts

There appea~s to be considerable difficulty in differentiating bet~een

respiratory inhalants "'hieh may be called '''fibrous'' as compared ~ith Inonfi­brous" substances. There is no problem when we consider substances such ascrocidolite, amosite, chrysotile, anthophyllite, fiberglass, rockwool, ornatural or synthetic textiles (wool, cotton, nylon, rayon, dacron, orIon,etc.). -These materials are predominantly composed of elongated delicate com­ponent elements whi~h are indisputably "fibers."

There appears to be no absolute definition of what constitutes a fiber-­neither with mineralogists nor with textile experts. Review of discordantterminologies almost leads one to the conclusion that a fiber is a fiber whenit is obviously so. Physicochemically speaking, hO~·lever, a fibrous mineral·"lould be a subs tance '''ith a propensity for cleavage in !:lyO planes of space.­Some mineral fibers cnn, however, also form when aluminosiloxane sheets aretIro lleo" to fort'l tubu les.

Sporadic and possible spurious attempts have been made to classify miner­als such as talc or tremolite as fibrous dusts. This is apparently on thebasis of three properties:

1. There is the fact that talc and tremolite are mineralogically classi­. fiable as si1icates~ as are most fibrous minerals such as the asbestos series.

2. Some samples. of.. talc and tremoli te contain a minority of oblong par­ticles which are considerably longer than they are thick. These elongntedparticles are only 'very rarely true "fibers ll in the conventional sense and aremore properly designated spiculeS, rods, or needles.

. ,

3. It is a fact that some talc or tremolite depcsits occur geolo~ic~lly

in close juxtaposition to chrysotile or other ore bodies so that some contt!mi­natio~ of talc with serpentine, do~omite, maGnetite, pyrophyllite5, and cloysmay occur.

The logic in designating any nonfibrcus silicate C~ fibrnus, for ~l~

latt'.:!r evll'l reOJsons, sOlllchoH evades thi$ author. If this pri~ciple \-lere~prlicd to other substnnces, there would be no sen~ibl~ W&y to classif~ n~ncr­

als or cnviro:'lfficntal contaminants_ For c>:a"a?le, hemiJtitite Clr m.:gncsit·~ or.:!sarc often "cont~min<lted" ·.-d.th si liceous m:tt;cri<tls, b:) til fioro'.15 and cr:::; :.11­lin~_ Coni often contnins mico, clays, asbestos, silica, etc. Do thcs~

Oldmixturcs justify clossifying hematite as al'lythiD~ oth.:r than hem.nite:

magnetite ~s anythin~

but magnetite; coal canything except coal;and so forth?

Perhaps the soluticn li~s in s~b~lass

fying the s1 licate-materials (table 1) ~

,those which 'belong toan asbestiform grouparid those that are notprimarily asbestifo~

in nature. '!his maymake mineralogicalsense and may agreewith some of the bio­logical propensitiesof these materials.Such a classificationmay also be extendedto embrace mineralsand te~ti les, \·;he·thernatural or synthetic.

12- .

12+

4xO-­

2xOH-

r-I 0~ ~ 0]I

" 6 x 0--.

,\,,

\\

\_:~

l..E..1L£JIiII,

~o

o 0o ::.

/'--l~: : cliO",- .

Cll.- __ G,

III

I,I ,, ,,,

1+

I_J

-... .., -.- 0 --- --SILOXANE---- -_ .. ----. _.

-1-------------

$llOXANE-j

--- --- --- .. III

.4xO-­

2~OH-

IxK+ 6)(.0--FIGURE 1. - Diagram of the cluminc-siloxone templates C'f

silicates.

16 + I'~ : + I-~~-';-I •I •

4x Si++++ : I

II

I+~

16+' ~--,I:...t....:J ,,4x Si+++4 I

III,,

10 - I~ ~ : 0]..,\ \,.,; ,,,

\\-

,To resolve these

issues it is nacessa=rto take a c!ose~ lookat the physicoche~ic~l

relationships of the various silicate minerals. These substances were all ­formed in nature because of certain highly characteristic coordinative proper­ties of silicon, oxygen, and aluminum atoms. l{nen the earth's crust wasformed, these atoms sought one another to fom the "subs tr<:lte" for varietiesof silicates. This substrate is the alumina-siloxane moiety formed in allsilicates (fig. 1). Individual silicates differ from one another accordin£ towhether and hO\o1 certain other elements such as iron, magnesi\r.t, manganese,sodium, and calcium become irlterposed in the "micropo"res II of the siloxaneframe .....ork and the degree to which and the manner in \V'hich these silo:::anes archydrated. This is a highly complicated although virtually fully decocied sci­ence. Indeed, because of the advanced state of the science of silic~te chem­istry, it al~eady is industrially possible to synthesize a number of thesemultibillion-year-old natural silicate minerals--though not yet at suffi­ciently lot.. cost to be competitive with m1ner:t1 silicates. for our presentpurposes it is pertinent to· sum:narize that, based on the ahlminn-sih~){'lr:~ tem­plate concept, there is a precise phy:c;i.cochemicnl exp lonntion \;1\1 s11 i -.:atcminerals arc pr6sent in nature as microporou5 cry~tal1ine substances, ershe<.>.tlikc tubul&lr, ribbon or lathlike, oblong~tc, acicular. er fibrous r:-.il1er­also ,\ cl~ssifieation of the silicates on the basis of chi:; t'rincipl~ i~

presant~d in tnble 2.

52

TABLE 1. - Tibro~s respirable ~crosols

Natural Synthetic:MINE?-.AL

Silicate:AsbestiforrnCrocidoliteAmositeAnthophylliteChrysotile

Nonasbe~tiform

TalcTremoHte

: Nonsilicate: Brucite

Silicate:FiberglassRocbvool

Nonsilicate: Potassi\~ titanite

TEXTILECottonWoolHairSilk

NylonDacronOrlonRavon

- Silicate minernlsTABLE 2.Nicroporous crvstalline I Tuoular or ho llo~..r!

Laminar: Hydrated:Analcite ChrysotileChabazite EndelliteHeulandite

:Fibrotl!i : i\ntro li te Anhvclrous: H~ll ..wsi.teSheetlike I Ribbonlike

Aluminou$;: IAttapulgiteHdntmorillcnites SepioliteHontu:ori 1100i te

IP:lli~orskiteI

Ncotrooite Oblon~ particulat~

Hectorit"e TrclTIoliteSClponitc Acicular

1-1ic<1c.eous Sericite

"Bi~tite 4\n tigor He

Illite Sil1i::lanitc

Huscovite Fi brous

Phlogopite Ac tioo lite

Vermicu li te An thopll)' Lli te

Pyrophyllite. Amosite

Crocido liteKilolini cesKaolin

I

Ac tino li t~ ,

Non"~ 1u;ainous: Talc IIt is to be noted that lE1£ is here cl<lssificd :1$ a shectlike silicatc

whicli is in a group quite separate fro:n other laminar silic:Jtes cr from trcmo­Utc ,...hicll is often 'llso called tfJlc. 13ccouse talc (!lg::JSi.;O':;,(Ollh) lacks thealuminl.l:l1 ;l!;orM; \:h icil h:wc such a streng 1y bcodinl; efi:ec t bct~"Jcen the '>i lo:::m~

53

tJU l )'",.. ",-1 C". ll'lyorfli, tnet. tole.•1 \il:l1t.f: 'fc::uH 1.:-- splits {It:'irnari11 and r-!'('dCl~in~ntl::

. along one plnne of space to fot'::1 fine larr.in:l. Hom~ver, cl~avage ~l("ln; the :\:0other·p13nes of space occurs second~rily. Thi~ provides for the fine divisi­bility of talc. The nonadherence of the fl~t rartlcle surfaces to on~ anotherfurnished the Ifgreasy" or "slippery· property of talc. Scanning elcctt:'onmi.croscopy has \-1ell demonstrated this flaky character of the talc particle(fig. 2).

Trcmolite also is often classified as talc, perhaps ~ccause it also lacksthe aluminum atom. Since two calcium atoms substitute for alt.tr:linum, trer.loli::.ebelongs mineralogically with the amphiboles (which all have achicv~d co~?ar­

l'ble substitutions). -It has t~e empirical formula: C~Hg:;Si9022(OHh. Froi:1the· point of view of its siloxane structure, tremolite ·differ~ frcr.l talc inthat it cleaves almost equally readily in two planes of space whereas cleavag:in the third plano-f"s a secondary" feature. For this reason the classicaltremolite particle is cuboidal to oblongate instead of platelike (fig. 3).A minority of tret!\(llite "crystals" c le.:lve lESS we 11 in the third dir:1cn~ion

than they do in the other two. These particles th~n manifest as stiff rods 0:­

needles. For this reason the appropriate location of tremolite in table 3lies between the sheetlike silicates and the .acicular silicates (sericite,antigorite, and sillimanite). The latter habitually cleave in such a mannerthat their" natural format is a short needle or rod.

The amphibole minerals, as mentioned .:lbov~. ha.... e substituted oth~r ele­ments for aluminum. Thus in actinolyte and Clnthophyllite both mngnesit.:.":1 end

FIGURE 2•• Electron microphotogrolll ofl:lle shOVlin;) its lominarchoroc:~r (X 7,500).

FIGURE 3•• t.\i:::rC'Fhotc~roi)"oi :yoic::;oblolla Ircmoli:c CYVs:c!::.

~ "

(I.lognificoliOn ullk~,:,,, n.)

54

iron are present (HgFe).,Sil!l0:;}O! (OH)2. In crocidolite there are both sodium cmdbivalent and trivalent iron (NaaFe;3Fe;3SisO~~(OH)3).Amosite is a mixture ofactinolite' and anthophyllite. Aluminum is absent from all of these. Theircleavage in relation to the siloxane substr~te is predominantly and equally intwo parallel planes. For this reason, they occur in nature as elongatedfibers, which will bend rather than break in the third spatial plane. Con!;e­quently, these fibers have high tensile strength ~nd flexibility whic~ is ~Ji~j"

they are so industrially important.

~BLE 3. ··Pathogenicity of silicates

Rating.°01234.56789

.!'lineralsMontmorillonite, kaolinite, talc, tremoIite •Talc + an;igorite, magnesite, dolocite, and spinelloTremoli~'with many rods or needles.Sericite, antigorite, sel1imanite, mica.Chryso~i1e.

Actinolite .Anthophyllite.Amosite.Crocidolite. .Asbestos +·silica or other minerals.

Chrysotile is unique among the nonalucinum-containin; silic~tes. Itsempirical formul~ is N~Si40lC'(OH)e0 It is classifi~ble as.a tubular or hol­low silicate. Its siloy.~ne template, hO'olever, is basically a sheet whichbecomes rolled upon itself to form a tube. For this reason chrysotile isclassifiable with endellite which is rolled in the opposite direction. I,hendehydrated to form halloysite the prior endellite tube splits lengthWise toassume °a ribbcnlike or lathlike form. It then rese:ubles the silicntes,attapulgite, sapiolite, and paligorskite.

lvhat does all this have to do with the biological properties of talc?Prob~bl)' a great deal. Thes.~ physicochemical char~cteristics of the varicussilicates are the base-sfor their particulate size, their ease of entry iutothe respiratOr)· system,· their penetration into cellular and intercellulartissue elements, their retention in or elimin~tion from tissues, their solu­bilization, their chelation or interaction ~ith other ele~ents within the bio­logical system, and their acceptance or rejection by living matter. Thesebiological counterparts may now be .examined.

Differential ~iological Prori~rties of Silicate Minerals

ntere arc marked differences bet\Jeen the cDp~cities of the individu<31cl~sses of silic:1te minerals to pr:>voke resiH'\uses in hll~£In anu :lnil:l:ll ti::;sues.There also ~re major misconceptions as to \-Ihn\: these substances can do wheninhaled by mnn or other mammnls. 1\:0 of the most ~:xtremc of the~c arc(1) that all siliceous minerals are equ£llly pathcgenic Dnd (2) thnt there iseven the lenst sembl<1occ bet,Jeen the effects of the asbestifor~ and the non­~sbestiform silic~tcs.

55

To express these differences in a practic~l manner onc ~~y ~ccor~ a per­centile value of pathogcnicity to e~ch substance. Since it is not really pos­sible.to discriminate biol6gical responses with complete precision, a seale ofzero to 10 may suffice. My appraisal of the differential p'athogenicity of thesilicate minerals is recorded in table J.

Since there .are in the medical literature disease c3t~:;ories sl1eil .:lS talclung or talc pneumonconiosis, many exp lanations are needed to c larify ~;hr talcand tremou. te (as pure substances) have been given e zero rating and ,;l1ychrysotile asbestos is c-Iassified at the lower .end of the' pathogenic spectrur.lwhereas crocidolite and amosite asbestos are at the opposite end. Since it isextremely difficult to disprove a Jack and the Bean Stalk 'myth, multiplefacets of th~ problem need be explored. '

.'·'It is necessary' to examine more closel)" the or:qp.ns and the errcneous

premise that all s,!.:u.catc minerals are equally injurious. The loose use ofthe. terms asbestos or asbestosis and the facile identification of oth~r

amphiboles with "asbestos" may be a factor. HOl,r did this come about?

Part of the problem originates in the manner in ,·:hich physici.:ms r.:akediagnoses of conditions such as "asbestosis" or the techniques used in dra.":la­tizing a description pf newly identified disease entity. Often the diagnosisis not based,on,precise,and painstaking verification of the pertinent issues.Net uncommly, loose association and coincidence are the guiding criteria. ­Careful work histories are not always taken, so that a lu~g lesion fou~= in anemployee of a certain industry mny become identified ~ith tile final'occupation,whereas it might have had its origin in nocuous dust exposures encountcrt::d ina prior unrelated decade. Far too often the isolated rClre e~~otic e~ali!ple isthe sole basis for the generic concept of a "net,r" pnel'illoconiosis. The e:,:cep­tion becomes the rule. Even unrelClted disease, such as tuberculosis or .mycosis or sarcoidosis have been ~isidentified as nevY pne~~oc~nioses) ~e~ely

because they occurred in an e:nployee of the suspected occupation. This Frob­lem has been discussed more fully else~here (1-1, ~).

Pneumoconiosis usually is identified during life through radiography.The radiologist wh~~xpertly examines "shadol"s" of lesions mu:>t rely cn thepathologist who has studied necropsy specimens. The latter often is quiteuncritical of the source of his material and not uncommonly quite peorlyinformed in the field of pneumoconiology. In the entire United SC;2tes '.;ithits thous<lnds of excellent pathologists. there· are probably not core than ahalf a dozen true connoisseurs of this eclectic branch of fcrensic medicine.,TIlis may be true also in othei countries. Io make a reliable identification.the pnthologist must not only have. had years of e?Cperience in decoding thistype of man-rna'de disease. but must also have <lCCCSS to appropri~te microsco?y,chemi stry. and I'~ trographic equipment· :lIld ~ki 115.

It <llso is quite> unusual to encounter "pure" caSES of <l particulardisease. Industrial wor~ers. especially in A~eric~! tend to be quit~ ~obile.

rfll'j' shift frem one trade to ancther :md pct~nti:ill:; r~c':!i':e !:::.:l(:i;>l~ :::.:;::0"slln~s so th.1t the pneumoconiosis which ulti!':l.:1l:ely e:ncrges often is a r;lClni- .-..festatioll of a prior dust or chemical cxposur~ or D cCffipositc of many

.6.,

56

5ucc'l."ssive eXI"0~urcs to diverse .agents, sC''l'le cf which r.J:ly not even be sepa Q

r~tely pathogenic, but which may produce disense through the principle (Ifpotentiationo The phenomenon of individual susceptibility often also is over~:

looked and disease, which develops in an unusual isolated case among manyunaffected employees, is seized upon as a "typical ll e,:amp le of ho\,r dangerousthe suspected silicate may be. Sometimes insufficient heed is paid to thequestion of dosage. Almost any substance is harmful in ovcr'ilhcloling amounts.Even substances which are biological necessities· can be harmful in excessiveconcentration. We all need oxygen but cannot survive perpetu~lly in an allO~7gen environment without aaverse results. Our bodies need water, but~our

tissues can "dro.vn" "therein. So it is "dth "inert" minerals. If a worker isgrossly, recklessly, and long exposed to almost any dust, the pulmonarydefenses will be overcome and harm wi11 result. This p~int is well illus­trated in experiments for instance with fiberglass utilizing the intratrachealversus the inhalation tes.hniques. If a 'quantit}O of glass fibers is injectedinto the lungs of animals, gross pulmonary lesions swiftly follow (fig. 4).Whetl, however, the same g"lass particles are inhs'led in smaller dai 1y dosagefor' periods of up to 2.years, no disease is induced ev~n though the totalamount of glass inhaled may greatly exceed the amount introduced as a singl~

"slug" (fig. 5).

FIG.URE 4•• Pulmo;,\tHy lesion inducedwithin 4 months in a gl!inco pigby intratracheal il1jcstlol1 of 1m9 of glass fibers in successive

40).

FIGURE 5•• Loc:k of pulmonary resp~ps~ Ie

gloss fibers inhaled 00 i Iy byguinca pig for 1S month:,; ill cr.ocrcsol concentration of 1 ;!:gper cubic f~ot of 0 ir (X 40).

Careful analysis of die minernlogic COli1PNiition cf tho;! lungs and the wor:histcriE:s of dec-cased 1nd1:1strial >~orkcrs with various grades of silicate­induced disease h.u shO'"m that "pure" examples of specific silic<ltosE"S :Areextremely rare. It is almost a,dO:""..atic that if any ndvanced grades of diseas(

. are found :Among workers in silicate industries, the causative agents :Are cul­tiple and likely to have potentiated each other's adverse propensities. Forthis reason the worst examples of severe pul~onary fibrosis or other lesionsgenerally fall in category 9 as shown in table 3. A typical exa~ple cf sucha severe mixed silicatosis is illustrated 'in figure 6.

are found among workers in silicate industries, the causative agents are mul­tiple and likely to have potentiated each other's adverse propensities. Forthis reason·.the ""orst examples of severe pulmonary fibrosis or other lesions'generally fall in categorr 9 as· shown 1n table 3 •. A typical·exa.lIple of such~ severe mixed sili~atosis is illustrated in figure 6.

/'

Pure crocid6rite or amosite pneumoconioses are rarely found in A~ericatoday. They used to be common in England 30 or more years ago and of courseare specifically associated with South Africa. The severe disease (category lor 7) which these intensely and relentlessly fibrogenic silicates cause(figs. 7 and B) has strongly influenced the image of lIasbestosis." fordecades crocidolite pneumoconiosis was asbestosis. The problem is that whenthe 'Jord lIasbestosis" is today used in relation tC' other fit:rous silicatessuch as chrysotiIe, the horrible image of crocidclite pn~umoconiosis is con-jured up. . -

Indeed, it is extremely difficult to find examples of pure chrysotileasbestcsis. Host ' ...orkers with advanced pulmonary diseC\sc ~vho are said to ha....echrysotile asbestosis usually have had prior or s~condor: exposure to othersilicates, silica. and other minerals or chemicals.

The few rare cases of pure chrysotile asbestcsis are n££ charncterized bygross pathology such as is found \I1i th amosi te or crocidoli te asbestosis(fig. 9). Chrysotile 'pathogenicity is, therefore, given a value of 4 on thescale of 0 through 9•

.... .The only hu!!'an e~:amples of tremoli te or talc pneu"'r.oconicsis which have

been placed on record were caused by tremolite "hich contninecl a high propor­tion of needles or rods or talc ,..hich tJas signific<lntly adulterated with othe:­minera.ls such as trcmolitc (C8:2Hg~ (0l1)2Si::30~:?L dolomite (Ca;:g(CO:;)2), spinel:(NgAlaO.. ), ma.gnesite (HgC03 ) .. magni!tite (~e203)' .mtigorite (Hg(OH).~Si.• O.. :).chromite. (FeCr~04)' etc. The amount of d~sease seen in these cases even afterproionged e:·:posure is mini~al (f.i~. 10). Pnthcgenicity r:ttings of 2 and 1have been accorded these aberrant .vnriants of tremolite and talc.

Pure t.:llc. HS.jSi..O,:, «(jU)~, :tppcars t·) he liio1::-gica 11)' inert. It is true:th:>i. the mineral con be fC'und in the lunh~ :Ifter sir;llific:.nt prolonged cxpo­~ure, but it is simp1)' here as a stored r:l:lterial. llist010gicall}' thi::: is atl.1CS<lUrosis only 'l:ithout <lny thestlurisn:osi!J (for cxnlllple. c)"togenic, cytotoxic,or fibrc:gcnic renct~on to the talc particles).

For this reason t;llc is iJccor.dc.J ;; ZE'rc !)Jthogcnicity r:lcing <:J1ong ,,riththc clnys .:lna k.:tolin. 1'rcmolitc .:1150 bell'ngs here W:lcn it r.occurs .:s oblongcrys tn Is \~i til ;'l minor i ty of rods or need 1.::s .

FIGURE.7•• Dense interstitial fibrosiscaused in hllman lung byexposure to cro:idolitedl!st (X 1).

FIGURE 8•• Subpleural and interstitial pul.monary fibrosis caused in manthroughcxrcsure to crocidolilcand omosile (X 1).

FIGURE 9. - Limited "reaction of the humanlung lothe inhalation ·of chrys­ot i Ie dus t for 22 yeors as amincr on d mi II worker (X 1).

FIGURE 10. Limited human p::th·olog)' chor:Jcter izin;exposure to- impur~

tremolila dust for 1~

years (X 1).·Histological Graciation

The differentinl biological potentialities of the silicates a~e also.. recognizable on his tological review of "p'.1re II examples of human ~~:pcsure.

Starting l-lith talc the examples of tissue reaction sho\VTI in figures 11 t

13 clearly demons trate the inert nature of this mineral. The close crotldingof the myriads of talc particles, which ar~ brilliantly revealed by polarizeclight microscopy,-is··typical. The individual represented in the X-ray hadworked in an automobile tire manufacturing factory for 2 decades and duringall of this time he l·las r.egularly and heavily e~posed to talc dust. He thenleft this industry to take employrnentfor 11 years in 3 nond~sty tracie. Henever developed synptoms during life. He ~ied follc\"'ing an au to::'lObi Ie acci­dent. TIle talc lesions wer~ discovered on routine review of the tissues a~c

the work history as described was reconstrccted retrcspectively. Th~ lack oftissue rene tioll, pnrcicularly the lack of fibrogenesis, corre lat.:!s t.'c 11 withthe symptomles::; st:lI:e dltr~ng life. There is no di'!:nage to the bronchial orvascul.:Jr clements and alveolar sp·oce. pleura, oU.lel regional lymph nndesrernnincc.l unaffc:ct~J despite thc abu:lclnnt i'rcsencc of 1:;11c particl~s ~round orin thesc lung COII\IH'li£:utS. The number of talc pOlrtic lcs j)l!r uni t squ:t.e areaof lung ti::;suc Olt st:1nclnrd magnification is inversely proportion:ll to thetissue rC:lctivlty to silicates. The excessive dysr:1tio of pOlrticles t.) celIelar or intcrstiti~l.ti::;sue is about as grcnt as one may cver observe ~nd

serves as rin iIll.J~x of biological inertness of t:1lc. "By s\.lbsequ.::nt petro­srOlphic and X-:"-.'· <iiffraction cechniq":Jes the' tCilc retained in the lung tissci:

60

FIGURE 11. - Microphotograph of talc: par­ticles in the olveolar wall of the humanlung, rendered visible by polarization oftransmitted ·Iight grode 0 th~saurosis

(X 1,000).

FIGURE 12. - Microphotcgraph ct· tore: par­ticles in the hum::m bronchia I I}'mpr.node, ·.. isualized by pobri<:otion mi­croscopy, grode 0 thesaurosis(X 1,000).

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FIGU.RE 13•• Transmitted light micropho­rograph of Inc alveolor-wall in a man....,ltlJ hod been o:::cupotior.ol/y ~r.posed

fa talc dusl for 20 years, grade 2.thesaurcsi s (X 1(0).

61,

of this case '-las shcnm to be an appro::dm<:l.tcly 70 percent talc and 30 percenttremolite mixture. This case, therefore, further demonstrated the inertnessof tremolite and proves that tremolite does not potentiate any latent patho­genicity which talc may have or vice versa.

, -n\e next example shows that tissue reaction in a talc ~orker who had beenexposed for a protrac ted period to talc llhich contained a varia ty of irl?u:-i­ties including tremolite rods, clays, and silica. The w~rker remained essen­tially sympton free during approximately 24 years of exposure to this dust.His death was due to a myocardial infarction about 7 years after retirement.Three 'features are evident by contrast with the first case (fig. 14) ~ Firstthere is patchy or minimal inter~titial fibrosis of alveolar walls. Second~

collars of dust-filled cells may be observed in the l)~ph channels aroundsmali blood vessels and bronchiles. Third. occasional ferruginous bodi~s canbe· seen in the areas of fibrosis (fig. 15). TIlere is minimal distortion of,.-the air spaces and some focal pleural sclerosis. This grade of tissue pathol-ogy is, therefore, no longer a thesaurosis or mere storage response. such as

,was secn in the case of pure talc exposure. We are now dealing with an'example of early thesaurismosis or true tissue reaction to stored dust butwithout physiologically discernable adverse effect. This class of responsetypifies mineral or grade 1 reaction to the silicate dust.

The stage 2 pneumoconiotic reacticn is characterized by a quantitatiy~ly

greater prevalence of the abnormalities sC!cn ,,,ith stage 1. There are about:twice as m~ny fibrotic plaques in the alvcclar walls (fig. 16). Thcre is

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fiGURE 15•• Ferruginocs bodies re ... eo iedby Perl's slain in c::Jse lS(X 1,000).

0'''. .,

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F.IGURE 14 •• Fecnl lesions in human II!ngof on employee wilo hod been exposed10 dust conloillillg tulc, trcmolite,clo)', r.md sUic::!. Grode I silicOlosis(X 1(0).

fiGURE 16. - Grade 2 si lico~osis in a humonlung after prolonged occupationalexposure to tremolite containingo high proportion of rods or nee­dles (X 100).

fiGURE 17. Typicalfocallesioncousedbyprolonged inhalation of chrysotilefibers, grade 4 si licatos is (X 100).

r

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-,...

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FIGURE 18. - Chrysotilc body as vi'Suolizedb)' fronsmi lied Iig ht. Nole thesplintered clubli~e ends ofthe body (X dOD).

FIGURE 19•. ChrYSOlile body sho·...·jn'; t:,eferrcpro!e in:::JCcous moiler inIhe copsule orcund the c!ays­(II i Ie fiber, Perl's si:::J in

400),

. minimal Glveoloar space ~nd bronchilar distortion.displayed no s)~ptoms durin& life desrite his kno"~

trernolitcf Hhich contained about 20 percent rods and

63

the Fatient had, however,prolonged exposure toneedles.

Chrysotile dust inhalation, when unaccompanied by other exposures, causesslightly more reaction than that-just described. This is grade 4 biologicalreactivity. There now is more involvement of alveolar walls and characteris­tic spidcrlike Dr cctopuslike lesions are found (fig. 17). The chrysotilefibers are quite characteri~tic and may be found as chrysotile bodies (fig. 18)which also stain viVidly blue and in typical dumbbell fashion with Perf'sstain (fig. 19) .. Under ail immersion X 1,000 magnification bare chrysotilefibers of great delic.:1cy may also be visualized (fig. 20)." There is fairlydiffuse pleural thickening and slight perivascular, and peribronchiolarfibrosis is discernable ,throughout. Siight airspace distortion is evidenteven though there was no macroscopically or physiologically detectable emphy­sema. This man had wor~d' as a chrysoM.le mi llcr for approximate ly 23 }'earsand had' never'been exposed to any other dust, having formerl)" been a farr.ter inQuebec Province. Detailed physiological analyses vere inconclusive for func­tional deficits. No diffusion defect: was .revealed. The: reason for this isreadily evident when the relationship of the alvcol~r fibrosis to the ~lveolar

fibrosis to the alveolar capillaries is analyzed (fig. 21). Since thp. capil­laries remain intact on the alveolar surfaces, no physiological impairment hasresulted except for minimal stiffening of the lungs ~ith sequential minimallyincreased breathing effort. Gas exchange has remained unaffected.

Such cases of pure chrysotile exposure arc "1~trct:'lely r<1re. Hore usuallythe disease is the culmination of dust exposures Ivltich occurred during a mixedc~reer of mining and ~articipation on other dusty occupaticns. Depending onthe variety in the mixture of dusts and the intensity and duration of exposure.

....FIGURE 20•• Bare chrysotile fibriis imbed­

ded in fibrous tissue ..... ithin on alveolorwoll of 0 chrysotile miller, hlosscn tri.chrome ·stain (X 1,200).

·64

FIGURE 22.· Inter!>titiol lesion representa­tive of grade 6 si/icatosis. Pr%rl~d

occupalional exposure to anthophrllitcdust'(X 10).

~

FIGURE 23. - interstitial pulmonary lesionrroduc:cd by pr c longed expo­Slife 10 croc:id"lite. Grode 8silicotosis (X'lOl.

• • I ::.•.••• fI,

.:..... ;. ~, • 'J

FIGURE 24 •• Inlerstitia/reaction 10 mixcdsi/icocndchrysotile dust ex­pcsure. Grade 9 sii iC:J~os i~iX 10).

65

all gradations of tissue reactioD frem 5 through 9 may be found (figs. 22-24).Strongest potcnti3tion is be~veen si!ic~ (quartz) ~nd .chrys~tile) as happensin the 'transit pipe industry. The lung tissue bcccrnes diffusely and dens~ly

carnified leaving very little viable and functional lung. This happens rela­tively s\viftly and the tragedy" is that the fibrcgenic proces~ goes on relent­lessly long after exposure to dust has ceased. 1bis silica destroys whatchrysotile avoid:> anti vice versa.

The lesions produced by arnosite or crocidolite acting alone are verysevere (grades 7 and 8). :Characteristically the fibrous,amosite or crocido­lite fibers seek out perivenous) perilcbular, and pleural lymph and tissues .(£ig.25). Dense sclerosis results in a weblike m~nner, thus producing severe,pulmonnry res tric tive damClge. There is so tTr.lch fibrous tissue .that the CoU ',:::.:::

tiye crocidolite fibers are relatively scarce and difficult to detect, espe-~'

cially'since these fibers are less'£errophilic than the less hnrmful chryso­tile fibers (fig. 26). Proliferation of pleural mesothelium is a classicalsequel to crocidolite exposure which lends to neoplasis (mesotheliomn) in a

'high proportion of cases (fig. 27).

Experimental Evidence

The differential pathogenicity of Silicates has been e~perimentally

~robed by this author and several others. Some results of personalresearches have been published <,2,), bet much additional data re'!lain to bereported .

. One of the principle experiments ~3S to c~plore the ccmparative effectsof fibrous and nonfibrous types of silicates ano to evaluate the pathog~nicity

of long versus short fibers and ball-mi lled fiber less silic?tes. Tilt:! intra­tracheal, intravenous, intracardiac, intracerebral, intraoeu lar subcutaneC'us _and inhalation routes were utilized by this author. Others have cx?eri.Ple:ltedadditionally with the intrapleural and intraperitoneal routes. Rats, guineapigs, rabbi ts, and monkeys \o1ere the prin,cipal experimental subjec ts of thisauthor. Others have. also conducted expc'riments em mice, cats, dogs, anohamsters.

Talc has consistently stood out in all experiments as an i~ert material.It could be injected into diverse tissu~s in relatively large quantities with­out evoking the lenst reaction. When introduced into the blo~dstream, talc\vas still found cir~lating freely after 18 months. In this respect tolc dif­fers ~adicO\l1)" froo silict'l (as quartz) t:hich vanished fror.l the blooclstrc.:l:awithin hours after intravenous or intracardi::lc introduction.

1'11(' c~:p('ri.t::cl1t t·:i.th t:llc.: was litni.t~tl to ., stud\' uf :':11~ t't)1\(ibr('~t~ for::l ofthc silic:ltc:. ::0 fl.br0us talc \·l<1S ("lJt;:;inabl~ :Iud by t::1C ;!f~r::lL:ntior'·=='!;i:,:,.<;ico­

chc:nic.:tl.dl.lfinition probnbly does not l:~ist.

Trcmolite could be ~tu::Hed in hoth its rClrtic;t:l~te nnd rod or f!c~dlc forr::.As <t particulate \""r{aht (~'lcn when there' t,ere up to 5 perccnt rods) trcl.!I..'l.iteprc\'ed t:itolly inert. I\!; the proportion ,-'f H"ds to1ClS incr~ascci, 0bOllt: 20 pt.:rccntof fcc:11 lesions \·~ere dcmnnstr<:lble :in the experi:-:lcnt.Jl :lminills. Intratr;;cl!c<:ll

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FIGURE 25•• Proliferotion of perivenoustissues in person occupo·riono/.lyexl=osed to omositcdust (X 100).

FIGURE 26•• Typico I crocidolite tiber inpulmonary lesion (X 400).

-'", .

Pleural mesotheliomo whichdeveloped after prc!on\;cdexpOSlJre to crociooli!cex 100).

FIGURE 27.

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67

, linjection induced significant pulmonary patholog)', By inhalation p hO~JeverJ

the trcmcli te proved re htivety innocuous p even though some! fibers ,"eretrapped 'in alveolar phagocyt~s and converted to "trem9lite" bodies (fig. 28).Although these bodies resemble those of ~sbestos, the tremolite bodies do nothave the ominous significance of the asbestos bodies. When the effects ofshort tremolite rods (less than 5 microns) \·7ere cC'mpared "·ith long rods (20 toSO micromc tel's) an {nteres ting,. resul t \·UIS obtained. The short need l£:s prcv~c

inert. Tne long tremolite rods induced tissue reaction. This emphasized the'fact that it is not the ch7mical composition which is the basis for biologicalreactivity to the silicate' but only the elongated shape o~ particles ~hich

furnishes a pathog'enic stimulus.

Comparable results were obtained with anthophyllite and chrysotile. Longfib~rs (20 to 50 micro~ters) consjstently indu:ed pulmonary lesions in allexperiments. These varied in severity according to dose or duration. Whenfibers' were milled to less than 5 micron length neither of these silicatesproduced significant,Pathological r~pon5es in experimental animals. Thisreaffirmed' the principle that it is the length of the anthophyllite or chryso­tile fiber particles and not their chemical composition which serves as thep~thogenic stimulus.

This author has not had co:nprehensive personal experience '-lith theeffects of amosite or crocidolite on experimental animals. The few exp~ri­

ments personally performed and review of the sparse literature on this subjectconfirms, however, 'that these t\.70 'silicates are significantly more pathogeni-cto diverse animal species than is either anthophyllite or chrysotile. Thisreaffirms the high pathogenicity classification offered in table 3.

FIGURE 28•• Tremolite body located with­in alveolar space of guinea pig fol­lowing prolonged dcily inhalationexposure ot ce:-nccntration of 1 mgper cubic root of air (X 400),

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, 6,8

A further principle was ~rouzht ~ut in parallel ex?~riments viti. fiber­glass. Inhalation by guinea pigs of 10nB and short fibers did not result ininterstitial fibrosis. These glass fibers were 5 microns or more in caliber.An experiment perfol~ed with fibers less than on~-twentieth of this dlameter(average 0.2 micron) resulted in sisnificant: pulmonary fibrosenesis. Thisresult suggests that the bio~gical activity of glass in particular and per­haps othl:!r fibrous silic61tes may be a product of either the particle lengcn orparticle di~~eter. It is not known at this stnge if this principle wouldtruly apply to all fibrous silicates. Nor is it kno~~ ~hether length and fine­ness of fiber caliber can:potentiate each other in produc~ng tissue responses.'The latter experi~ent still needs to be performed. There is, however, som~

human evidence that this may be the case. The electron microscope has inrecent years be~n app~ied to the study of pneumoconiotic lesions. Throughthis instrumental modality'it has" been possible to demonstrate large nu~bers

of' extre.'Yte ly fine asbes tos fibers wi thin pulmonary fibrotic les ions \o!hichappeared almos t devoi,a- of "asbes tos bodies" as visualized by convention;] Ioptical microscopy. Electron microscopy has also revealed' that there are manydelicate fibers among conventional-sized fibers normally discernable inasbestos dusts as viewed by maximum magnification optical microscopy. Si~ilar

fine submicron fibrils have not been observed in specimens of talc or tre~o­

lite. The prescnce of these ul tramicroscopic components in asbestos mil~erals,

therefore, constitutes.<:I further explanation for the great differences' bct\-ieenthe biological actions of the tales and asbe~tiform silicates.

Carcinol!enicitv

The controversy ovear the carcinogenicity -of sorne asb~stos ~inerals <lnathe applicability of this to th~ tales now requires closer e~amination.

The propensity of crocidolite and areosite to evoke neoplestic responsesin.man has been a well-documented phenomenon fo~ more than half a century,requiring ;llmos t no fur cher elaboration except the follmdng com."':ients:(1) TIlcre is today less lun;; cancer in crociciolitel:orkers than fO!T:lerly

·.be:::aus~ of improved dust control; (2) pleural mesotheliomatosis has recentlyemerged as an important neoplastic seque It to crocidolite exposure; (3) the~e

is an enhanced prevalence. of cancer of nonpulmonary tissues in e~p loyees ofcrocidolite industriei; (4) cigarette smoking and ur~sn air pollution have inrecent years surf~ced as a complicating i.ssue, so that there may no\v be SO::1edoubt whether all cro~idolite-associatedneoplasia is exclusively due to thecrocidolite; (5) inhalution ~xperimenr:s ~ith crocidolitc have not been con­vincing in demonstrating ncoplasiogenesis; (6) lmplantation studies, espe­cially pfeural space deposition'of large quuntities of crocidolite, have sho\'Da positive cClrrehtion betvl1en oncogenesis and crocidolite dos<l;;e; (7) thelatter observation is mitig~tcd by th~ eY:..EerUilental deI:10nstr41tit:>D th<:lt ordi­na.tily_nonc <lrc i. nogeni~ sub~ t:t.,nces, such as _9u~r.~_z__~~I:_~. C~'ln .:,)~~ prodUCt! .~ ~;:l,.1-m9s..Qthe liom.:tto.s is, ~"l) _that the jl1eura! re~ron5~_"~~_ ~n _" sens~

nons..rec if i C,Ao

Arnosite ~rob3bly)also is carcinogenic though perhaps not as clecisi'.·\~l)' asis crocidolite. There <:lIso is some question uhether the crocidolite or n:':1:>­site arc in themselves carcinogenic or ~·:hether other chemic~ls, with \Jilicn

69

these fibers are impregn~ted or InineralogicallY,~ssociatedare th~ or.cogenicagents. Benzpyrenes and eancer-producing metal salts (arsenic, nic~el,

beryll1~) have been demonstrated in crocidolitc and amosite ores.

Nothing comparable has'4Seen demonstrated for talc or tremolite. Becausethe latter has been classified as an amphibole mineral, it has n~tu:ally comeunder su~picion as a theoretical carcinogen. Theory and fact,· ho~ever, havenever matched up in either human e~perience ~r animal e%perimentation. Fordecades workmen have be~n engaged in talc and tremolite mining or milling orhave been expo~ed to talc products in secondary industries eoploying talc andtremolite as ~lippage agents or fillers or for insulating purposes, etc.Excess prevalence of lung cancer-" which cC'uld not equall)' reasonab ly have beenaccounted for in terms o~ ~xposure to cigarette smoke, urban 'pollution or toprior, cencurrcnt, ~~ sequential exposure to true asbestos, has been convinc­ingly recorded.

One of the c,arlier epidemiological surveys of tremolitc miners in Net-!:York State did hint at an enhanced incidence of lung cancer among relativelyyoung, 45- to 55-year-old, employees of selected mines. This was a disturbingobservation. Ro••ever, subsequent surveys of toe sar::e miners have sho.m a dis­tinctly lo\>'er incidence of neoplasia even though the miners now ."ere' an aver­age of I decade older with commensurat~ly lenger tre~olite ex?osur~ and,ofcourse, with longer periods of cigarette s~oking. Two c:-:planations ma'" clar­ify this change, TIle first is that the average level ~f ciustiness in thetremolitc miners hod been appreciably reduced durin~ ~he past 2 decades.Prior to the institution of vigorous dust control. it ...as not uncnr::non to findmine and mill workers smothered in cloud~ of tre~clitc d~st--particle ~cu~ts

probably having been 100 to 1.000 times gr~ater than ;,e:ts r~cently been per­mitted. The second feature uncevered by detailed analyses of the ~ork histo­'ries of the tremolite industry employees of the prior era (that is before1955) shewed that with rare exceptions all these e~ployees h~d s?ent a l&rgepart of their ~orking lives in industries other than talc mining, tlany hadbeen exposed to asbestos or to rock nnq metal ere dusts. Analysis of th~ lun;tissue of a representa.~ive number of these cmp loyce~ confi nled the presence 0;quartz, asbestos, metals, and other substances. Tnis clearly creatad deubtwhether the earlier epidemiological findings hav~ true validity wi~ respectto trcmolite.

The 04.11eged carcinogenici ty of chrysotile. \>,hich is r.1ined in the vicinit·:of one of the ntojor tremolite deposits in NOTth At:leric~, has been un :1(,1di- .tierial confusing factor. Persons \.iilO are not thoroughly far:liliar "'it:1 therather major Mineralogical and bioloiical differ~nces between tre~olite andchrvsotile rna", h.,vc been confused l;>y the geolC'p.ical close association of theseore' bodies Clnd the cn:oncous Clssumption th~t both tre::tn} itc nnd cbr"'snti Ie <lr~asbestos min<.>rals. ":Ie loltter issue h<ls Lllrc ..dy been discussed and· it h-:,sbeen cstClc.lishe<.l that, although trcmclite liI:1y be e:t~l :1."':lphib"lclike substancesuch as antho!,hyllite, affiositc. or crocidolite, th~rc arc no premises for:'Issumiog that tremclite is likely to bchan~ biologicall..- as do the ~ther threeamphiboles,

Is chrysotile a carcinogen? This is a'very perplexing question. Acrescendo of popular opinion has sought to incrimin,Jl:e chrysotile. Thisauthor. remains unconvinced. The main premise for carcinoge~icity stems f~

epidemiological observation of employees of the insulation and shipbUildingindustrie~. In both these industries there has been in the past considerableexposure of pipe laggers to a.abes tos dus t. On 1::; in recent decades. hom!'lcr,have these insulation bats been composed predoninantly of chrysotile. Informer years crocidolite and amosite were important components. Studies oflung tissues of deceased laggers have verified the presence of amphibole aswell of serpentine asbestos. Which then was the carcinogen? It is a kno\vnfact also that in recent years fiberglass has,to an increasing exten: begunto substitute for asbestos in this industry. The increasing demonstration oflung cancer in insulation workers" coincides with the latter event. Whichagent then is the carcinogen? It is further knot..on that insulation workershave during decades become heavily exposed to ~eth~~~hJ~_"~one-typesolventsin the synthetic glu€s presently used" to bond the bats of asbestos or fiber­glass to the pipes or ducts ~ich are being insulated. Formerly the glues didnot co~tain such highly volatile solvents. Indeed, one of the occupationaldiseases of significance in this industry nO\11 is polyneuropathy due to theinhaled ~olvent vapors. These solvents come in dirac t contac t Yi th respira­tory epithelial surfaces, whose lipid surface membranes and organelles arehighly vulnerable since they are readily solubilized into meth}'lethyl ketonesor similar solvents. Which then,is the true carcinogenic substance?

Finally, it should be pointed out that the role of cigarette smoking hasnot been satis fac torily discounted in the referenced epidemio logica 1 studiesof lung cancer aI1)ong insulation workers. In scUte groups reported an e~cess 1

prevalence of lung cancer ~as not demonstrable when cigarette smoking wastaken into consideration. Epidemiolcgical surveys of chrysotile workers inQuebec sho\"ed no excess of lung cancer. A re'!'ie\\' of pl-aurall,esothiliC';:tatosisin Canada also failed to focus attention on Quebec or any other center wherechrysotile industries are concentrated.

There also is conflicting experimental evidence about chrysotile. In onepersonally conducted s~~dy the theoreticdl carcinogenicity of chrysotileasb~stos was probed by an inhalation study in \\"hich .tumor induction in ratsexposed to berylli"um sulfate (a potent carcinogen) '''as cC'rr:pared with tu.-norrates in rats similarly exposed to cllrysotile dust ~nd to chrysotile followingberyllium sulfate and also to chrysotile dust exposure preceding exposu~e toBeS04 • The results were striking (1.1). In "the berylli~n group the meanincidence of lung cancers was.IS.4 percent. in rats exposed to both chryso­tile 'and BeS0-l" the malignant tumors totnled only 8.5 p~rcellt. No tumorsdev(:lopecl in rZlts which ~ere exposed only to chrysotile .md there were none inunclosed controls ob:;er,,~d for 24 months. 'Ihis clearly nhm:c; thnt so far fromchr~:sotilc :'ICtillg as a carcinogen or :J5 t.l coc~rcin('gcn tlith :1 r.no\,'TI pot!:ntCZlTciu,:,gen. the chrysoci.le behaved like nn <1nticnrcinog~n \Jith respect 'to thebcq·llium.

lIention may also l:>e tn:ld(: of ansynthetic chrys0tile deposited intoci;Jted uith SOIl:C tUlIIor production.

('~perir:1ent conducted \dth n.:r.tur4l1 vcr·susthe j'1t1ur411 sp.:!cc. The l.1ttcr W;)S 4lSS0­

The synthetic chrysotile had the cO:ltr=try

71

effee t (1). The difference between the two is th3t n<:!.tural chrysotile Sc.:r.e=times is cont~min"'ted wHh metallic salts abs~rbcd b)· the serpentin~ tibersurfaces or perh3ps trapped within the chrysotile tubules •. Some of thesemetals include known carcinogens such as nida~l, chromium, aud arsenic. Si:'lcethese metals are not universally present 1n equal degree in all sar.li'les ofchr)·sotile, cnution must be-l1sed in sti6ffi~.tizing this miner~l unnecessarily'a carcinogen. It should also be stressed th"'t the intr~pleur~l expEr~~ant 5

highly artificial so that cancer production by this technique may be e~?ecteQ

with true c3rcinogens as ~ell as with substances which are not ordinarily car­cinogenic for man (for example silica). The .demonstration, therefore, that .synthetic chrysotile, natural tremolite, and talc are incapable of evokingpleural mesothelio!is may be highly significant testimony ·that these sub­stances may not possess latent carcinogenic properties for ma~.

Sequelae and Complications

. Carcinogenesis has been separately discussed since it is not establishedwhether it is an independent property of carcinogenic minerals or a scquel or'complic<:1tion of the pneun:.oconiotic pathology induced by these silicates.

It is necessary to review several principle sequelae and complica~ions ofexposure to dusts.

The firs t is tuberculosis. The c lose association be t,,:een pulxl'onarytuberculosis and silica inhalation has been convincingly estlblished throughepidemiological studies and experinental inquiry ~nd the pathcgenicprinciplesfor tuberculogeqesis by siliceous minerals has probably been fully clar.ified(1). Do the silicates also promote the development of ?ulm::mary tuberculosis?There is no real epidemiological evidence ror this and no lacoratory proof.Tohe relatively closed co~unities i~ South Africa where crocidolite and a~o­

site are mined .me processed and th~ compar~bly closed corrmunity i::1 Qu~l:.ec

where chrysotile is produced constitute excellent epide~iolobical r:lQt::els. ~io

significant excess of tuberculosis has been demonstrated for these occuFa­tional groups whose life careers could b~ follp~ed to a s~tisfactory degree.A large number of these..miners and mill workers ,"cre personally studied bythis author and a nuinber of necropsy specimens ,·:ere like~·'ise examined. :Bycontrast with s~li~a workers, tuberculosis was consistently conspicuous by itsabsence or infrequency.

Since the pathogenic asbestiform silicates proved nontuberculcgenic. itis no surprise that tuberculosis has not been·associated ~vith talc nnd t:-~o­

lite minir.g. Of 300 mine and mill workers '-lho have be~n follo.ved c-:er thepast 25 years not <:1 single individual developed tuberculosis. This is <l::l.a~azins record. ~hich speaks for itsclf since tubcrcull)sis is by nu mcens aconquered discase, eSFccially a-nong i.ndustrial '''I~r.I:crs.

He::lrt Discnsc

There are no indications thOle <:trtcriosc lerotic hc."rt discOlse i:. any ;::orcprevalent in asbestos ,,;orkers th<:t11 in the general pop',lL<ttion. The ir.cidc::l.ceindeed i'lppear::i to be lo'W'er. This mClY be d'Je to thc e:,CC:i$ l't'e'Jalcncc of cor

FIGURE 30. - Perivascular fibrosis show­ing stenosis of pulmonary bloodvesse Is. Silica ond asbestosexposure (X 10).

..

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'II,. 'II

.... ...0." ..... • .~ J,. ,~y. ~ ~.,. }.

f " .'. f,? • i ,

Q

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":...,,'.

,. .... FIGURE ·31. • Asbestos bodies in wall of

blood vessel os demonsfroled byPerl's stain. Mi)(ed omosite cr.dchr)'solilc e:-:posure (X 10-).

73

pulmonal~. The latter constitutes ~ significant Frobl~m and has a directexplan~tion in th~ perivenous pulmona~y fibr~sis and elastosis and the conse­quent destruction of the v~scular system (fibs. 29 to 31).

In tremolite workers some cor pulmonale does occur. This is usunlly.traceable to prior, concurrent, or subsequent e~posure to asbestos du~t.

Revie\07 of the life histories of 300 tremolite employees sito~.,s an incice,~ce of8.3 percent of the fatal cardiac disease. This is not signfficantly differentfrom the occurrence of arteriosclerotic heart disease among age-matched con­trol groups that never \"er'e exposed to tremolite. Less i~ knc~., about'pur~

talc industrial ·groups. The lack of epidemiological data at least establishedthat thus far no problem has surfaced.

Emph'1sem'a, Bronchitis, and Bronchiectasis

So many industrial agents cause emphysema and/or bronchitis (!) that aninquity about this matter seems pertinent.

Th~re are no indications that. either emphysema. or bronchitis .are-.se.lec-'ti"ely more prevalent among ..asbestos .. wot:ker~L th~;'l_ wi th . the.- gener.a L E,.ub l).c.The underlying pathology induced by asbestos is not of such a nature as tofoster either of these conditions. There is no primary brC'nchcpathy and con­sequently no alveolar distension induced by obstruction. Nor is there alveo­lar r.lural destruction. The very nature of asb,:stcsis prote-cts the lungsagainst thi~, since the fibrous and elastic trssue in the alveolar wallsstrengthens rather than \Jeakens' these structures (fig. 23j. At a later stagethere rna)' be some compensatory emphysema as areas of the lung collapse. Thisis., however, limited and regional only_.

Bronchiectasia is another matter. It is quite;: CClTl.':':cm Sequel of pro­gressive interstitial pulmonary fibrosis in a~bestosis. The bronchi ~nd

.bronchioles are distended by the contraction of fibrous tissue in the pulmo­nary parenchyma bet\;een them. This ferm of lung pathology may be seen as alate sequel of crocidc1 itl:l, amosite, or chrysC'ti le asbes tosis. Un like bron­chiect3sis in,nC'noccupational groups, the asbestotic form of the diseas€ i~

initially nonsymptomatic because there is lU:ll~._ o_r no asso.ci~tcd infection .. . _--~ -----

Ho~e"er, the latter may occur later.

None of this is seen with. pure talc workers. There has been no e~cess

prevalence of either emphysema, bronchitis, or bronchiectasis I.,"less there hasbeen prior or concurrent or subsequent 'asbestos exposure. Precise epidemio­logical data are availnble for tre:no~ite \Jorkers. thus, of 26t. eOj)loyees fol­lowed since 19!.8 only four· developed cmph::sema. T~is reflects <1n incidence ofnpproxir.wtelj· 1.51 perce-nt. This is hr belCH the incidc:1ce of ernphyser.l<l inthe general populotion.· Bronchitis \:it:hout c:::':)h::~cr::.'J ~ias (\hs~r:ed in :ie'.".:nindividuals. No hronchicctasis uas found aeong these wct~ers. This clearlyShO~'l~ that talc and tremoli te not only b~have differently fro~l chrysotile,<:loosite. or crocidolita but may even be asscci<:ltcd \-lith ~ lo:·er incicJ~nce ofthese disorders ,,!lich no\-1 arc among tiH~ TllOSt I'rcv<llent and di~~bling illnessesi.n North AmuricCl. \~hC'th~r tole or trcmolitc prC"tect thci lungs :ll;.:linst

14

emphysema and perhaps bronchi~is seems D fair question to pDse and can beans"lered affirmatively on the basis of the above evidence.

Conclusion

World production of talc and tremolite currently exceeds 3 million tansr~r annum. These clearly arc useful mineral pro::!ucts which play an iIllpOl"t<:lntpart as fillers of asphalt, rubber and roofing materials, as components ofceramics, paints, insecticides, paper, textiles. ~all tiles, cement, stucco,wire and cab Ie coverings, or as foundry parting compounds., .A small proportion'of talc enters intb the toiletry and food processing industries. Throughth~se multitudinous uses thousands of human subjects com~ 'into contact ~ith

talc and tremol~te for every employee contributing to their production. Ar.er­ica produces and uses more than one-third of the ~orld production. It is dif­ficult" to imagine hOl,)' modern civilization can be sustained Without these use­ful and relatively inexpensive minerals.--

It seems fortunate, therefore, that talc <:lnd tremolite are so biolcgi­call)" inert. There .is a mood in the United States today to eliminate 211environmental hazards. No one can quarrel ~ith the humanitarian ideologyinspiring $uch enthusiasms. Too many hazardous materials have been haphaz­ardly released into the ·human environment and it would be better to controlall industrial substances equally to achieve maxim~m security. Not only doesthis seem logical. but it seems reasonable to counsel against restraints whi~h

'-7ill unnecessarily increase the cost of living for everyone or tl1hich may gUI:lup the l..orks somet.here along the line. After all. the human body. and partic­ularly the lungs. have some defenses. The lung constantly replaces itself aspart of normal existence. It would seem that·. al tho'ugh these defenses can beo.... eruhelmed through long exposure to asbestos minerals, this is not estab­lished for taLc or tremolite in modest concentration. This fact should betaken into consideration in formulating regulations for dust control in the.talc indus tr)·.

1. The physicochemi.cal relationships of silicates are revielved.Although there are superficial resemblances bet~een the empirical formul~s oftalc. tremolite. chrys~tile. amosite, and crocidolite. there <:lre signific~nt

physicochemical structural differences bet~een thcir respective molecules.

2. Mineral silicates may be best classif~cd in terms of their capacityto be formed as sheets, tubules~ ribbons, oblong crystals. needles. or fibersinstead of using the conventional mineralogical classifications of serpentinesor aophiboles or of asbest~fcrm minerals.

3. Talc ~nd tr.cmolite ~re biolgocal1:1 relatively inert substances ;lndthi.s contrnsts sharply with the marked path~£enicity of amosite and crocido­lite~ Chrysotile occupies an intermediate position. but its biologicDl p~o­

pensi tics <lrc c loser to those of talc nnd tremo li te.

4. Experimcntnl and epidemiological studies prOVloe closely confi~at(

data tdth respect to the points just mcr..tioncd. It is c.xtre:nely difficult tidentify lars'\! numbers·of employees who have been exposed exclusively to oneor another ~incral. Many pulmonary lesions in silicate-industry employees ~

composites of multiple-dust and chemical e~posures and many of the nocuousasents derive from sources other than the silicate industry in question.

5. Lung cancer has been definitely associated epidemiologically withexposure to crocido1ite. There is no evidence that talc or tremolite possesthe biological propensity to induce neoplastic lesi~ns. There also is somedoubt as to the role of chrysotile in carcinogenesis. Even though SO:':'le studies suggest that chrysotile may foster the deYelopment of lung cancer undercertain circumstances, other studies flatly contradict this evidence so thatthe issue still seems '·unresolved.

".,.;.

6. The sequelae and complications of exposure to asbestos include bron'chiectasis and. cor pulmonale. Obstruc.tive bronchop~thy and emphysema do notnonnally occur ~s a consequence of exposure to asbes~os. Talc and trernoliteexposure are d~void of any of these pathological responses:

1.. Grclss, P. Fibrous Dust SeminCir Industrial Hygi.ene Foundation of A:n!~rica.

Hedical null., No. 16, 1.910.

2. Schepers, C. H. H. Biological Effects of Asbestos. Annals of th(! ~;~U

York Academy of Sci., 1965, pp. 121, 132, 246, 385,437, 504,596, 599,601.

3.1962.

Chron.ic Berylliosis. Archiv fijr Getverbepath .und Gewerbeliyg, v. 19,

4. Industrial Bronchitis and Asthr:1a. Ind. Nedicine and Surgery,. v. 24, 1955, p.. 52..

5. SilicosfS and Tuberculosis. Ind. Nedicine and Surgery, v. 33,1964, p. 381.

6. Thesaurosis Versus Sarcoidosis. J~~f v. 181, 1962, p. 635.

7. Tumors of Primates and Rodents. Ind. Medicine and Surgery, v. 40,1971, p. 48.

8. Schepers, G. ~L lI. f and T. H. Durkan. TIle Effects of Inhalec Talc Nini:ngDust 00 the Human Lung. ~!A Archives Industrial Health, v. 12, 1935.p. 182.

9. . An E~pp.ri~cotal Study cf the Eff~cts of Talc Dust on Animal Tissue.AHA Archi\:~s Industrial Health. v. 12, 1955, p. 317.