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In rorm:ation Circular 8639

Proceedings of tIle SYlnposiui:n on Talc,


"'l
hSllington, 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
MINES
Thom;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 fibrous


minerals (for eYoample, crocidolite) mny be associated with· excess prev31~nce.
of malignant neoplasia of the lung, and even of Qther organs $uch as the
st~mach or colon, has focussed attention on the biological potentials of all
the fibrous minernls. For reasons not quite clear to this nuthor, talc has
somehow and proba~y quite unjustifiably become embroiled in the issue of the
carcinogenicity of asbestiform minerals. "Talc, though a silicate, is by no
means a fibrous mineral.

It is quite important, however, to thcr~ughlj review biological reactiv-


ity to tales because their industrial uses are so diversified. Direct hUQan
exposure is consider2ble, involving all elements of humanity, practically fro~
cradle to grave. There also is a contradiction betHeen the strin(;ent rules
for dust suppression in mining or milling of talc and the almost total lack of
controls 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 concern-
ing the biological action of talc and compare this with what is knmm about
·the adverse properties of other silicates ~id especially th? asbestiforrn
minerals.

The biological potentials of a variety of natural and synthetic silicates


have b~en personally r"esearched over the pas t J dec<ldes. TItese studies have
included investigation of human subjects, experimental animals, and a review
of the literature •. Jltiman studies include observaticns on crocidolite and
arnosi 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~n
subjects studied e:-:cecds 10,000. These stlldies are e\'alu<lted against a back-
ground of famili3rit)' through personal clinical experience and res~arch cf the
pathogenic action of a variety of other natural nnd synthetic siliceo'..!s, non-
siliceous, and chemic"l aud synth"etic subs t<lnces. nl(:~ clinical subjec ts
exceed JOO,OOO and necropsies have been per.formed on over 10,000 dece~~ed
industri~l workers.

Animal studies l'n'/e recentl)' been reviet.:ed in a publication on Tu~lors of


Pfinlntes ~nd Rodents (2). These included researches C'n the biological proper-
ties of 1.07 industrially ir.lportant: OIaccri.o.ls through cxp~rirnental c::-:posures of
7,906 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 OOO
papers have been reviewed. If' these do not include ~ll that has been written
on this subject of pneumoconiosis p any omissions would be unintentional.

For practical purposes all references cannot be cited nor will it be


reasonable in a paper of the intended scope of this presentation torecapitu-
late all that is kno~~ about the biological actions of talc and fibrous envi-
ronmental 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 Inonfi-
brous" substances. There is no problem when we consider substances such as
crocidolite, amosite, chrysotile, anthophyllite, fiberglass, rockwool, or
natural or synthetic textiles (wool, cotton, nylon, rayon, dacron, orIon,
etc.). -These materials are predominantly composed of elongated delicate com-
ponent 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 discordant
terminologies almost leads one to the conclusion that a fiber is a fiber when
it 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 are
tIro lleo" to fort'l tubu les.

Sporadic and possible spurious attempts have been made to classify miner-
als such as talc or tremolite as fibrous dusts. This is apparently on the
basis 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 par-
ticles which are considerably longer than they are thick. These elongnted
particles are only 'very rarely true "fibers ll in the conventional sense and are
more 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!mi-
natio~ of talc with serpentine, do~omite, maGnetite, pyrophyllite5, and cloys
may 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.:!s
arc often "cont~min<lted" ·.-d.th si liceous m:tt;cri<tls, b:) til fioro'.15 and cr:::; :.11-
lin~_ 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~
1+ but magnetite; coal c
anything except coal;
16+' ~--,,
I:...t....:J ,
Cll.- __ G,
I
I I
r-I 0~ ~ 0] 12- . and so forth?

4x Si+++ 4
I
Perhaps the solu
I
I ,I " 6 x 0--. ticn li~s in s~b~lass
I ,I ,, fying the s1 licate
,,
I
_J
I
,, -materials (table 1) ~
--- -- - ... .., -.- ,those which 'belong to
I~ ~ : 0]..,\, \,. ---- -_ .. ---- , /'--l~: : cliO"
0

10 - SILOXANE an asbestiform group


; ,, . _.- .
arid those that are not
, primarily asbestifo~
.4xO--
\ -, 4xO--
in nature. '!his may
1------------- -j ,,
\
2~OH- \- 2xOH- make mineralogical
\
sense and may agree
--- -- -
$llOXANE
--- .. I \ with some of the bio-
16 + I'~ : + I-~~-';- I •
I
I
I
\_:~
l..E..1L£J 12+
logical propensities
of these materials.
I • Such a classification
4x Si++++ : I
i
I may also be extended
I
I
,
I
to embrace minerals
and te~ti les, \·;he·ther
I+~ ~
o
oo ::.
0 natural or synthetic.
,
IxK+ 6)(.0-- To resolve these
FIGURE 1. - Diagram of the cluminc-siloxone templates C'f issues it is nacessa=r
silicates. to take a c!ose~ look
at the physicoche~ic~l
relationships of the various silicate minerals. These substances were all -
formed in nature because of certain highly characteristic coordinative proper-
ties of silicon, oxygen, and aluminum atoms. l{nen the earth's crust was
formed, these atoms sought one another to fom the "subs tr<:lte" for varieties
of silicates. This substrate is the alumina-siloxane moiety formed in all
silicates (fig. 1). Individual silicates differ from one another accordin£ to
whether 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 siloxane
frame .....ork and the degree to which and the manner in \V'hich these silo:::anes arc
hydrated. This is a highly complicated although virtually fully decocied sci-
ence. Indeed, because of the advanced state of the science of silic~te chem-
istry, it al~eady is industrially possible to synthesize a number of these
multibillion-year-old natural silicate minerals--though not yet at suffi-
ciently lot.. cost to be competitive with m1ner:t1 silicates. for our present
purposes it is pertinent to· sum:narize that, based on the ahlminn-sih~){'lr:~ tem-
plate concept, there is a precise phy:c;i.cochemicnl exp lonntion \;1\1 s11 i -.:atc
minerals arc pr6sent in nature as microporou5 cry~tal1ine substances, er
she<.>.tlikc tubul&lr, ribbon or lathlike, oblong~tc, acicular. er fibrous r:-.il1er-
also ,\ 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: Silicate:
Asbestiforrn Fiberglass
Crocidolite Rocbvool
Amosite
Anthophyllite Nonsilicate: Potassi\~ titanite
Chrysotile
Nonasbe~tiform
Talc
TremoHte
: Nonsilicate: Brucite
TEXTILE
Cotton Nylon
Wool Dacron
Hair Orlon
Silk Ravon
TABLE 2 . - Silicate minernls
Nicroporous crvstalline I Tuoular or ho llo~..r
!

Laminar: Hydrated:
Analcite Chrysotile
Chabazite Endellite
Heulandite
:Fibrotl!i : i\ntro l i te Anhvclrous: H~ll ..wsi.te
Sheetlike I Ribbonlike
Aluminou$;:
Hdntmorillcnites
Hontu:ori 1100i te
I
I
I
Attapulgite
Sepiolite
P:lli~orskite
Ncotrooite Oblon~ particulat~
Hectorit"e TrclTIolite
SClponitc Acicular
1-1ic<1c.eous Sericite
"Bi~tite 4\n tigor He
Illite Sil1i::lanitc
Huscovite Fi brous
Phlogopite Ac tioo lite
Vermicu l i te An thopll)' Lli te
Pyrophyllite
. Amosite
Crocido lite
Kilolini ces
Kaolin
Ac tino l i t~ ,
I

Non"~ 1u;ainous: Talc I


It 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 trcmo-
Utc ,...hicll is often 'llso called tfJlc. 13ccouse talc (!lg::JSi.;O':;,(Ollh) lacks the
aluminl.l:l1 ;l!;orM; \:h icil h:wc such a streng 1y bcodinl; efi:ec t bct~"Jcen the '>i lo:::m~
53

ll'lyorfli, tnet. tole.•1 \il:l1t.f: 'fc::uH 1.:-- splits {It:'irnari 11 and r-!'('dCl~in~ntl::
tJ U l )'",.. ",-1
C".

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

Trcmolite also is often classified as talc, perhaps ~ccause it also lacks


the aluminum atom. Since two calcium atoms substitute for alt.tr:linum, trer.loli::.e
belongs 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:1
the· point of view of its siloxane structure, tremolite ·differ~ frcr.l talc in
that 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 classical
tremolite 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 3
lies between the sheetlike silicates and the .acicular silicates (sericite,
antigorite, and sillimanite). The latter habitually cleave in such a manner
that their" natural format is a short needle or rod.

The amphibole minerals, as mentioned .:lbov~. ha....e substituted oth~r ele-


ments for aluminum. Thus in actinolyte and Clnthophyllite both mngnesit.:.":1 end

FIGURE 2•• Electron microphotogrolll of FIGURE 3•• t.\i:::rC'Fhotc~roi)" oi :yoic::;


l:lle shOVlin;) its lominar oblolla Ircmoli:c CYVs:c!::.
~ "

choroc:~r (X 7,500). (I.lognificoliOn ullk~,:,,, n.)


54

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

~BLE 3. ··Pathogenicity of silicates

Rating .!'linerals
.°0 Montmorillonite, kaolinite, talc, tremoIite •
1 Talc + an;igorite, magnesite, dolocite, and spinello
2 Tremoli~'with many rods or needles.
3 Sericite, antigorite, sel1imanite, mica.
4 Chryso~i1e.
.5 Actinolite .
6 Anthophyllite.
7 Amosite.
8 Crocidolite. .
9 Asbestos +·silica or other minerals.

Chrysotile is unique among the nonalucinum-containin; silic~tes. Its


empirical formul~ is N~Si40lC'(OH)e It is classifi~ble as.a tubular or hol-
0

low silicate. Its siloy.~ne template, hO'olever, is basically a sheet which


becomes rolled upon itself to form a tube. For this reason chrysotile is
classifiable with endellite which is rolled in the opposite direction. I,hen
dehydrated to form halloysite the prior endellite tube splits lengthWise to
assume °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 varicus
silicates are the base-sfor their particulate size, their ease of entry iuto
the respiratOr)· system,· their penetration into cellular and intercellular
tissue elements, their retention in or elimin~tion from tissues, their solu-
bilization, their chelation or interaction ~ith other ele~ents within the bio-
logical system, and their acceptance or rejection by living matter. These
biological counterparts may now be .examined.

Differential ~iological Prori~rties of Silicate Minerals

ntere arc marked differences bet\Jeen the cDp~cities of the individu<31


cl~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 when
inhaled 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 is
even 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 per-


centile value of pathogcnicity to e~ch substance. Since it is not really pos-
sible.to discriminate biol6gical responses with complete precision, a seale of
zero to 10 may suffice. My appraisal of the differential p'athogenicity of the
silicate minerals is recorded in table J.

Since there .are in the medical literature disease c3t~:;ories sl1eil .:lS talc
lung or talc pneumonconiosis, many exp lanations are needed to c larify ~;hr talc
and tremou. te (as pure substances) have been given e zero rating and ,;l1y
chrysotile asbestos is c-Iassified at the lower .end of the' pathogenic spectrur.l
whereas crocidolite and amosite asbestos are at the opposite end. Since it is
extremely difficult to disprove a Jack and the Bean Stalk 'myth, multiple
facets 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 of
the. 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.:ake


diagnoses of conditions such as "asbestosis" or the techniques used in dra.":la-
tizing a description pf newly identified disease entity. Often the diagnosis
is 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 an
employee of a certain industry mny become identified ~ith tile final'occupation,
whereas it might have had its origin in nocuous dust exposures encountcrt::d in
a prior unrelated decade. Far too often the isolated rClre e~~otic e~ali!ple is
the sole basis for the generic concept of a "net,r" pnel'illoconiosis. The e:,:cep-
tion 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 Frob-
lem 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 the
pathologist who has studied necropsy specimens. The latter often is quite
uncritical of the source of his material and not uncommonly quite peorly
informed in the field of pneumoconiology. In the entire United SC;2tes '.;ith
its thous<lnds of excellent pathologists. there· are probably not core than a
half 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 this
type 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 particular


disease. 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
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 (If
potentiationo The phenomenon of individual susceptibility often also is over~:
looked and disease, which develops in an unusual isolated case among many
unaffected employees, is seized upon as a "typical ll e,:amp le of ho\,r dangerous
the suspected silicate may be. Sometimes insufficient heed is paid to the
question of dosage. Almost any substance is harmful in ovcr'ilhcloling amounts.
Even substances which are biological necessities· can be harmful in excessive
concentration. We all need oxygen but cannot survive perpetu~lly in an all
O~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 is
grossly, recklessly, and long exposed to almost any dust, the pulmonary
defenses will be overcome and harm wi11 result. This p~int is well illus-
trated in experiments for instance with fiberglass utilizing the intratracheal
versus the inhalation tes.hniques. If a 'quantit}O of glass fibers is injected
into 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 dosage
for' periods of up to 2.years, no disease is induced ev~n though the total
amount of glass inhaled may greatly exceed the amount introduced as a singl~
"slug" (fig. 5).

, .6.

FIG.URE 4•• Pulmo;,\tHy lesion induced FIGURE 5•• Loc:k of pulmonary resp~ps~ Ie
within 4 months in a gl!inco pig gloss fibers inhaled 00 i Iy by
by intratracheal il1jcstlol1 of 1 guinca pig for 1S month:,; ill cr.
m9 of glass fibers in successive ocrcsol concentration of 1 ;!:g
40). per 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 silicate-
induced disease h.u shO'"m that "pure" examples of specific silic<ltosE"S :Are
extremely 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 cul-
tiple and likely to have potentiated each other's adverse propensities. For
this reason the worst examples of severe pul~onary fibrosis or other lesions
generally fall in category 9 as shown in table 3. A typical exa~ple cf such
a severe mixed silicatosis is illustrated 'in figure 6.

are found among workers in silicate industries, the causative agents are mul-
tiple and likely to have potentiated each other's adverse propensities. For
this 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~erica


today. They used to be common in England 30 or more years ago and of course
are specifically associated with South Africa. The severe disease (category l
or 7) which these intensely and relentlessly fibrogenic silicates cause
(figs. 7 and B) has strongly influenced the image of lIasbestosis." for
decades crocidolite pneumoconiosis was asbestosis. The problem is that when
the 'Jord lIasbestosis" is today used in relation tC' other fit:rous silicates
such as chrysotiIe, the horrible image of crocidclite pn~umoconiosis is con-
jured up. . -

Indeed, it is extremely difficult to find examples of pure chrysotile


asbestcsis. Host '...orkers with advanced pulmonary diseC\sc ~vho are said to ha.... e
chrysotile asbestosis usually have had prior or s~condor: exposure to other
silicates, silica. and other minerals or chemicals.

The few rare cases of pure chrysotile asbestcsis are n££ charncterized by
gross 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 the
scale 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 propor-
tion 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 after
proionged e:·:posure is mini~al (f.i~. 10). Pnthcgenicity r:ttings of 2 and 1
have 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 a
tl.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 ,,rith
thc clnys .:lna k.:tolin. 1'rcmolitc .:1150 bell'ngs here W:lcn it r.occurs .:s oblong
crys tn Is \~i til ;'l minor i ty of rods or need 1.::s .
FIGURE.7•• Dense interstitial fibrosis
caused in hllman lung by
exposure to cro:idolite
dl!st (X 1).

FIGURE 8•• Subpleural and interstitial pul.


monary fibrosis caused in man
throughcxrcsure to crocidolilc
and omosile (X 1).
FIGURE 10. Limited human p::th·
FIGURE 9. - Limited "reaction of the human olog)' chor:Jcter izin;
lung lothe inhalation ·of chrys- exposure to- impur~
ot i Ie dus t for 22 yeors as a tremolila dust for 1 ~
mincr on d mi II worker (X 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 crotlding
of the myriads of talc particles, which ar~ brilliantly revealed by polarizec
light microscopy,-is··typical. The individual represented in the X-ray had
worked in an automobile tire manufacturing factory for 2 decades and during
all of this time he l·las r.egularly and heavily e~posed to talc dust. He then
left this industry to take employrnentfor 11 years in 3 nond~sty tracie. He
never developed synptoms during life. He ~ied follc\"'ing an au to::'lObi Ie acci-
dent. TIle talc lesions wer~ discovered on routine review of the tissues a~c
the work history as described was reconstrccted retrcspectively. Th~ lack of
tissue rene tioll, pnrcicularly the lack of fibrogenesis, corre lat.:!s t.'c 11 with
the symptomles::; st:lI:e dltr~ng life. There is no di'!:nage to the bronchial or
vascul.:Jr clements and alveolar sp·oce. pleura, oU.lel regional lymph nndes
rernnincc.l unaffc:ct~J despite thc abu:lclnnt i'rcsencc of 1:;11c particl~s ~round or
in thesc lung COII\IH'li£:utS. The number of talc pOlrtic lcs j)l!r uni t squ:t.e area
of lung ti::;suc Olt st:1nclnrd magnification is inversely proportion:ll to the
tissue rC:lctivlty to silicates. The excessive dysr:1tio of pOlrticles t.) celIe
lar 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 petro-
srOlphic and X-:"-.'· <iiffraction cechniq":Jes the' tCilc retained in the lung tissci:
60

FIGURE 11. - Microphotograph of talc: par- FIGURE 12. - Microphotcgraph ct· tore: par-
ticles in the olveolar wall of the human ticles in the hum::m bronchia I I}'mpr.
lung, rendered visible by polarization of node, ·.. isualized by pobri<:otion mi-
transmitted ·Iight grode 0 th~saurosis croscopy, grode 0 thesaurosis
(X 1,000). (X 1,000).

..

.. . ,
.;p'
• ~. 9
.. '
FIGU.RE 13 •• Transmitted light micropho-
rograph of Inc alveolor-wall in a man
....
'1/1'" "
" ....,ltlJ hod been o:::cupotior.ol/y ~r.posed
~f;~ fa talc dusl for 20 years, grade 2

·.l.. , .thesaurcsi s (X 1(0).


... '. ..,.. ,.
'c'
I..

•., .

.- d I

fro . . . . ''If' .,' :.a ,.. - '1

-
• ' •• ,\00"

"""'"
61,

of this case '-las shcnm to be an appro::dm<:l.tcly 70 percent talc and 30 percent


tremolite mixture. This case, therefore, further demonstrated the inertness
of tremolite and proves that tremolite does not potentiate any latent patho-
genicity which talc may have or vice versa.
, -
n\e next example shows that tissue reaction in a talc ~orker who had been
exposed for a protrac ted period to talc llhich contained a varia ty of irl?u:-i-
ties including tremolite rods, clays, and silica. The w~rker remained essen-
tially 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) ~ First
there is patchy or minimal inter~titial fibrosis of alveolar walls. Second~
collars of dust-filled cells may be observed in the l)~ph channels around
smali blood vessels and bronchiles. Third. occasional ferruginous bodi~s can
be· 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 but
without physiologically discernable adverse effect. This class of response
typifies 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

-,
; .
, , ,
". .. . ".
:~ '. :. "> ::-;
:' : , <, '1',· ::"'i:~ ,~; '41" I. ::." :'"

.e;;.'il"r,
.''" .': ':" ~'~ £': T\~~::', ;rjt~:' i
.
. ..
......
... .. \ l:,. .", _. :.... t. _."", :_."" .....

,.
-,

'.,
, ,.
0'''. .,
(II ':.. .... .0

..
F.IGURE 14 •• Fecnl lesions in human II!ng
of on employee wilo hod been exposed -.,_'=1" _'. ......" ...... _ .
10 dust conloillillg tulc, trcmolite, fiGURE 15•• Ferruginocs bodies re ... eo ied
clo)', r.md sUic::!. Grode I silicOlosis by Perl's slain in c::Jse lS
(X 1(0). (X 1,000).
fiGURE 16. - Grade 2 si lico~osis in a humon fiGURE 17. Typicalfocallesioncousedby
lung after prolonged occupational prolonged inhalation of chrysotile
exposure to tremolite containing fibers, grade 4 si licatos is (X 100).
o high proportion of rods or nee-
d les (X 100).
r
• I.. .....

!
...
'4

.:~
... ~

~.
<f»d'-

-,...

........
.,. .
...
FIGURE 18. - Chrysotilc body as vi'Suolized FIGURE 19•. ChrYSOlile body sho·...·jn'; t:,e
b)' fronsmi lied Iig ht. Nole the ferrcpro!e in:::JCcous moiler in
splintered clubli~e ends of Ihe copsule orcund the c!ays-
the body (X dOD). (II i Ie fiber, Perl's si:::J in
400),
63

. minimal Glveoloar space ~nd bronchilar distortion. the Fatient had, however,
displayed no s)~ptoms durin& life desrite his kno"~ prolonged exposure to
trernolitcf Hhich contained about 20 percent rods and needles.

Chrysotile dust inhalation, when unaccompanied by other exposures, causes


slightly more reaction than that-just described. This is grade 4 biological
reactivity. There now is more involvement of alveolar walls and characteris-
tic spidcrlike Dr cctopuslike lesions are found (fig. 17). The chrysotile
fibers 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's
stain (fig. 19) .. Under ail immersion X 1,000 magnification bare chrysotile
fibers of great delic.:1cy may also be visualized (fig. 20)." There is fairly
diffuse pleural thickening and slight perivascular, and peribronchiolar
fibrosis is discernable ,throughout. Siight airspace distortion is evident
even though there was no macroscopically or physiologically detectable emphy-
sema. This man had wor~d' as a chrysoM.le mi llcr for approximate ly 23 }'ears
and had' never'been exposed to any other dust, having formerl)" been a farr.ter in
Quebec Province. Detailed physiological analyses vere inconclusive for func-
tional deficits. No diffusion defect: was .revealed. The: reason for this is
readily evident when the relationship of the alvcol~r fibrosis to the ~lveolar
fibrosis to the alveolar capillaries is analyzed (fig. 21). Since thp. capil-
laries remain intact on the alveolar surfaces, no physiological impairment has
resulted except for minimal stiffening of the lungs ~ith sequential minimally
increased breathing effort. Gas exchange has remained unaffected.

Such cases of pure chrysotile exposure arc "1~trct:'lely r<1re. Hore usually
the disease is the culmination of dust exposures Ivltich occurred during a mixed
c~reer of mining and ~articipation on other dusty occupaticns. Depending on
the 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 alveolor
woll of 0 chrysotile miller, hlosscn tri.
chrome ·stain (X 1,200).
·64

FIGURE 22.· Inter!>titiol lesion representa-


tive of grade 6 si/icatosis. Pr%rl~d
occupalional exposure to anthophrllitc
dust'(X 10).

• • I ::
.•.••• fI,

~
.: ..... ;.
, • 'J
~

FIGURE 23. - interstitial pulmonary lesion FIGURE 24 •• Inlerstitia/reaction 10 mixcd


rroduc:cd by pr c longed expo- si/icocndchrysotile dust ex-
Slife 10 croc:id"lite. Grode 8 pcsure. Grade 9 sii iC:J~os i~
silicotosis (X'lOl. 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 happens
in the 'transit pipe industry. The lung tissue bcccrnes diffusely and dens~ly
carnified leaving very little viable and functional lung. This happens rela-
tively s\viftly and the tragedy" is that the fibrcgenic proces~ goes on relent-
lessly long after exposure to dust has ceased. 1bis silica destroys what
chrysotile avoid:> anti vice versa.

The lesions produced by arnosite or crocidolite acting alone are very


severe (grades 7 and 8). :Characteristically the fibrous,amosite or crocido-
lite 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 chryso-
tile fibers (fig. 26). Proliferation of pleural mesothelium is a classical
sequel 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 personal
researches have been published <,2,), bet much additional data re'!lain to be
reported .

. One of the principle experiments ~3S to c~plore the ccmparative effects


of 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:! intra-
tracheal, intravenous, intracardiac, intracerebral, intraoeu lar subcutaneC'us _
and inhalation routes were utilized by this author. Others have cx?eri.Ple:lted
additionally with the intrapleural and intraperitoneal routes. Rats, guinea
pigs, rabbi ts, and monkeys \o1ere the prin,cipal experimental subjec ts of this
author. Others have. also conducted expc'riments em mice, cats, dogs, ano
hamsters.

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 with-
out evoking the lenst reaction. When introduced into the blo~dstream, talc
\vas still found cir~lating freely after 18 months. In this respect tolc dif-
fers ~adicO\l1)" froo silict'l (as quartz) t:hich vanished fror.l the blooclstrc.:l:a
within 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 of
thc 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.ite
prc\'ed t:itolly inert. I\!; the proportion ,-'f H"ds to1ClS incr~ascci, 0bOllt: 20 pt.:rccnt
of fcc:11 lesions \·~ere dcmnnstr<:lble :in the experi:-:lcnt.Jl :lminills. Intratr;;cl!c<:ll
. .
~

.. .' .
'0

~ '. ., .

FIGURE 25 •• Proliferotion of perivenous FIGURE 26•• Typico I crocidolite tiber in


tissues in person occupo· pulmonary lesion (X 400).
riono/.lyexl=osed to omositc
dust (X 100).

., .""",.,
.
·f
FIGURE 27. Pleural mesotheliomo which
, ,. ...
I ,.:. ·."'~··4' developed after prc!on\;cd
.... ~.:.- .~.
.. expOSlJre to crociooli!c
. • (1.

t""O , ~

ex 100).
0 .. ...

fa ,. t •

. .,
-'", . • 9 • • 0'

.'" ' .
•• 4 .'
o
. "." I'
.e . '.

.
'. ,

-
.. . . .
'0
....
e. , ••f .....
67

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

the trcmcli te proved re htivety innocuous p even though some! fibers ,"ere
trapped 'in alveolar phagocyt~s and converted to "trem9lite" bodies (fig. 28).
Although these bodies resemble those of ~sbestos, the tremolite bodies do not
have the ominous significance of the asbestos bodies. When the effects of
short tremolite rods (less than 5 microns) \·7ere cC'mpared "·ith long rods (20 to
SO 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 ch 7mical composition which is the basis for biological
reactivity to the silicate' but only the elongated shape o~ particles ~hich
furnishes a pathog'enic stimulus.

Comparable results were obtained with anthophyllite and chrysotile. Long


fib~rs (20 to 50 micro~ters) consjstently indu:ed pulmonary lesions in all
experiments. These varied in severity according to dose or duration. When
fibers' were milled to less than 5 micron length neither of these silicates
produced significant,Pathological r~pon5es in experimental animals. This
reaffirmed' the principle that it is the length of the anthophyllite or chryso-
tile fiber particles and not their chemical composition which serves as the
p~thogenic stimulus.

This author has not had co:nprehensive personal experience '-lith the
effects of amosite or crocidolite on experimental animals. The few exp~ri­
ments personally performed and review of the sparse literature on this subject
confirms, however, 'that these t\.70 'silicates are significantly more pathogeni-c
to diverse animal species than is either anthophyllite or chrysotile. This
reaffirms the high pathogenicity classification offered in table 3.

FIGURE 28•• Tremolite body located with-


in alveolar space of guinea pig fol-
lowing prolonged dcily inhalation
exposure ot ce:-nccntration of 1 mg
per cubic root of air (X 400),
.' .
. .~

, ;,J
,
".
..,
.
'.1Jl'I' b D ,•

.."'.«IIP' I:~
. . .... .-.1'!'
4
'"
et.,'::
.....,
.• ~.
~ : •·.. ·f·"'.. ~' .
~' ';:;'.:J: ......"\,..;. ~. ,:;;/)!
... c·~· 0 ~ ........ ~ ~ •••
, ~ • . _r.~ ,,\. '
. ~" 1 .d- '. ~ •• I •. '" .
....
'J' .1# . 1:3.'" f'
~·l.,l '..•. '\
, 6,8

A further principle was ~rouzht ~ut in parallel ex?~riments viti. fiber-


glass. Inhalation by guinea pigs of 10nB and short fibers did not result in
interstitial 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. This
result suggests that the bio~gical activity of glass in particular and per-
haps othl:!r fibrous silic61tes may be a product of either the particle lengcn or
particle di~~eter. It is not known at this stnge if this principle would
truly apply to all fibrous silicates. Nor is it kno~~ ~hether length and fine-
ness 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 in
recent years be~n app~ied to the study of pneumoconiotic lesions. Through
this 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!hich
appeared almos t devoi,a- of "asbes tos bodies" as visualized by convention;] I
optical microscopy. Electron microscopy has also revealed' that there are many
delicate fibers among conventional-sized fibers normally discernable in
asbestos 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\-ieen
the biological actions of the tales and asbe~tiform silicates.

Carcinol!enicitv

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

The propensity of crocidolite and areosite to evoke neoplestic responses


in.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 recently
emerged 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 of
crocidolite industriei; (4) cigarette smoking and ur~sn air pollution have in
recent years surf~ced as a complicating i.ssue, so that there may no\v be SO::1e
doubt whether all cro~idolite-associated neoplasia is exclusively due to the
crocidolite; (5) inhalution ~xperimenr:s ~ith crocidolitc have not been con-
vincing in demonstrating ncoplasiogenesis; (6) lmplantation studies, espe-
cially pfeural space deposition'of large quuntities of crocidolite, have sho\'D
a positive cClrrehtion betvl1en oncogenesis and crocidolite dos<l;;e; (7) the
latter observation is mitig~tcd by th~ eY:..EerUilental deI:10nstr41tit:>D th<:lt ordi-
na.tily_nonc <lrc i. nogen i~ 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)' as


is 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.cogenic


agents. 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. Because


the latter has been classified as an amphibole mineral, it has n~tu:ally come
under su~picion as a theoretical carcinogen. Theory and fact,· ho~ever, have
never matched up in either human e~perience ~r animal e%perimentation. For
decades workmen have be~n engaged in talc and tremolite mining or milling or
have been expo~ed to talc products in secondary industries eoploying talc and
tremolite as ~lippage agents or fillers or for insulating purposes, etc.
Excess prevalence of lung cancer-" which cC'uld not equall)' reasonab ly have been
accounted for in terms o~ ~xposure to cigarette smoke, urban 'pollution or to
prior, cencurrcnt, ~~ sequential exposure to true asbestos, has been convinc-
ingly 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 relatively
young, 45- to 55-year-old, employees of selected mines. This was a disturbing
observation. Ro••ever, subsequent surveys of toe sar::e miners have sho.m a dis-
tinctly lo\>'er incidence of neoplasia even though the miners now ."ere' an aver-
age of I decade older with commensurat~ly lenger tre~olite ex?osur~ and,of
course, with longer periods of cigarette s~oking. Two c:-:planations ma'" clar-
ify this change, TIle first is that the average level ~f ciustiness in the
tremolitc miners hod been appreciably reduced durin~ ~he past 2 decades.
Prior to the institution of vigorous dust control. it ... as not uncnr::non to find
mine 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 per-
mitted. The second feature uncevered by detailed analyses of the ~ork histo-
'ries of the tremolite industry employees of the prior era (that is before
1955) shewed that with rare exceptions all these e~ployees h~d s?ent a l&rge
part of their ~orking lives in industries other than talc mining, tlany had
been 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 deubt
whether the earlier epidemiological findings hav~ true validity wi~ respect
to 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 the
rather major Mineralogical and bioloiical differ~nces between tre~olite and
chrvsotile rna", h.,vc been confused l;>y the geolC'p.ical close association of these
ore' 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-:,s
been cstClc.lishe<.l that, although trcmclite liI:1y be e:t~l :1."':lphib"lclike substance
such as antho!,hyllite, affiositc. or crocidolite, th~rc arc no premises for
:'Issumiog that tremclite is likely to bchan~ biologicall..- as do the ~ther three
amphiboles,
Is chrysotile a carcinogen? This is a'very perplexing question. A
crescendo of popular opinion has sought to incrimin,Jl:e chrysotile. This
author. remains unconvinced. The main premise for carcinoge~icity stems f~
epidemiological observation of employees of the insulation and shipbUilding
industrie~. In both these industries there has been in the past considerable
exposure 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. In
former years crocidolite and amosite were important components. Studies of
lung tissues of deceased laggers have verified the presence of amphibole as
well of serpentine asbestos. Which then was the carcinogen? It is a kno\vn
fact also that in recent years fiberglass has,to an increasing exten: begun
to substitute for asbestos in this industry. The increasing demonstration of
lung cancer in insulation workers" coincides with the latter event. Which
agent then is the carcinogen? It is further knot..on that insulation workers
have during decades become heavily exposed to ~eth~~~hJ~_"~one-type solvents
in the synthetic glu€s presently used" to bond the bats of asbestos or fiber-
glass to the pipes or ducts ~ich are being insulated. Formerly the glues did
not co~tain such highly volatile solvents. Indeed, one of the occupational
diseases of significance in this industry nO\11 is polyneuropathy due to the
inhaled ~olvent vapors. These solvents come in dirac t contac t Yi th respira-
tory epithelial surfaces, whose lipid surface membranes and organelles are
highly vulnerable since they are readily solubilized into meth}'lethyl ketones
or similar solvents. Which then,is the true carcinogenic substance?

Finally, it should be pointed out that the role of cigarette smoking has
not been satis fac torily discounted in the referenced epidemio logica 1 studies
of lung cancer aI1)ong insulation workers. In scUte groups reported an e~cess 1
prevalence of lung cancer ~as not demonstrable when cigarette smoking was
taken into consideration. Epidemiolcgical surveys of chrysotile workers in
Quebec sho\"ed no excess of lung cancer. A re'!'ie\\' of pl-aurall,esothiliC';:tatosis
in Canada also failed to focus attention on Quebec or any other center where
chrysotile industries are concentrated.

There also is conflicting experimental evidence about chrysotile. In one


personally conducted s~~dy the theoreticdl carcinogenicity of chrysotile
asb~stos was probed by an inhalation study in \\"hich .tumor induction in rats
exposed to berylli"um sulfate (a potent carcinogen) '''as cC'rr:pared with tu.-nor
rates in rats similarly exposed to cllrysotile dust ~nd to chrysotile following
beryllium sulfate and also to chrysotile dust exposure preceding exposu~e to
BeS0 4 • The results were striking (1.1). In "the berylli~n group the mean
incidence of lung cancers was.IS.4 percent. in rats exposed to both chryso-
tile 'and BeS0-l" the malignant tumors totnled only 8.5 p~rcellt. No tumors
dev(:lopecl in rZlts which ~ere exposed only to chrysotile .md there were none in
unclosed controls ob:;er,,~d for 24 months. 'Ihis clearly nhm:c; thnt so far from
chr~:sotilc :'ICtillg as a carcinogen or :J5 t.l coc~rcin('gcn tlith :1 r.no\,'TI pot!:nt
CZlTciu,:,gen. the chrysoci.le behaved like nn <1nticnrcinog~n \Jith respect 'to the
bcq·llium.

lIention may also l:>e tn:ld(: of an ('~perir:1ent conducted \dth n.:r.tur4l1 vcr·sus
synthetic chrys0tile deposited into the j'1t1ur411 sp.:!cc. The l.1ttcr W;)S 4lSS0-
ci;Jted uith SOIl:C tUlIIor production. 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~ tiber
surfaces or perh3ps trapped within the chrysotile tubules •. Some of these
metals include known carcinogens such as nida~l, chromium, aud arsenic. Si:'lce
these metals are not universally present 1n equal degree in all sar.li'les of
chr)·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 car-
cinogenic for man (for example silica). The .demonstration, therefore, that .
synthetic chrysotile, natural tremolite, and talc are incapable of evoking
pleural mesothelio!is may be highly significant testimony ·that these sub-
stances may not possess latent carcinogenic properties for ma~.

Sequelae and Complications

. Carcinogenesis has been separately discussed since it is not established


whether 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 of


exposure to dusts.

The firs t is tuberculosis. The c lose association be t,,:een pulxl'onary


tuberculosis and silica inhalation has been convincingly estlblished through
epidemiological studies and experinental inquiry ~nd the pathcgenicprinciples
for 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 occuFa-
tional 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 by
this author and a nuinber of necropsy specimens ,·:ere like~·'ise examined. :By
contrast with s~li~a workers, tuberculosis was consistently conspicuous by its
absence or infrequency.

Since the pathogenic asbestiform silicates proved nontuberculcgenic. it


is 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 the
past 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 a
conquered 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 ;::orc
prevalent in asbestos ,,;orkers th<:t11 in the general pop',lL<ttion. The ir.cidc::l.ce
indeed i'lppear::i to be lo'W'er. This mClY be d'Je to thc e:,CC:i$ l't'e'Jalcncc of cor
.. .. ...
.. 0.",~ •
.~
...
J, 'II
.
.
,. 'II
y. ~ ~.,.
}.
?
f
• '.
"

f, \& . J.,
a:"
-.
i

FIGURE 30. - Perivascular fibrosis show-


ing stenosis of pulmonary blood
,
,. Q . ..: .. ......
~

vesse Is. Silica ond asbestos


exposure (X 10).

:"...,,'.

,
. .... FIGURE ·31. • Asbestos bodies in wall of
blood vessel os demonsfroled by
Perl's stain. Mi)(ed omosite cr.d
chr)'solilc e:-:posure (X 10-).
73

pulmonal~. The latter constitutes ~ significant Frobl~m and has a direct


explan~tion in th~ perivenous pulmona~y fibr~sis and elastosis and the conse-
quent 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 of
8.3 percent of the fatal cardiac disease. This is not signfficantly different
from the occurrence of arteriosclerotic heart disease among age-matched con-
trol groups that never \"er'e exposed to tremolite. Less i~ knc~., about'pur~
talc industrial ·groups. The lack of epidemiological data at least established
that thus far no problem has surfaced.

Emph'1sem'a, Bronchitis, and Bronchiectasis

So many industrial agents cause emphysema and/or bronchitis (!) that an


inquity 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 to
foster either of these conditions. There is no primary brC'nchcpathy and con-
sequently no alveolar distension induced by obstruction. Nor is there alveo-
lar r.lural destruction. The very nature of asb,:stcsis prote-cts the lungs
against thi~, since the fibrous and elastic trssue in the alveolar walls
strengthens rather than \Jeakens' these structures (fig. 23j. At a later stage
there rna)' be some compensatory emphysema as areas of the lung collapse. This
is., however, limited and regional only_.

Bronchiectasia is another matter. It is quite;: CClTl.':':cm Sequel of pro-


gressive interstitial pulmonary fibrosis in a~bestosis. The bronchi ~nd
.bronchioles are distended by the contraction of fibrous tissue in the pulmo-
nary parenchyma bet\;een them. This ferm of lung pathology may be seen as a
late sequel of crocidc 1 itl:l, amosite, or chrysC'ti le asbes tosis. Un like bron-
chiect3sis 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 has
been prior or concurrent or subsequent 'asbestos exposure. Precise epidemio-
logical data are availnble for tre:no~ite \Jorkers. thus, of 26t. eOj)loyees fol-
lowed since 19!.8 only four· developed cmph::sema. T~is reflects <1n incidence of
npproxir.wtelj· 1.51 perce-nt. This is hr belCH the incidc:1ce of ernphyser.l<l in
the general populotion.· Bronchitis \:it:hout c:::':)h::~cr::.'J ~ias (\hs~r:ed in :ie'.".:n
individuals. No hronchicctasis uas found aeong these wct~ers. This clearly
ShO~'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 of
these disorders ,,!lich no\-1 arc among tiH~ TllOSt I'rcv<llent and di~~bling illnesses
i.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 be
ans"lered affirmatively on the basis of the above evidence.

Conclusion

World production of talc and tremolite currently exceeds 3 million tans


r~r annum. These clearly arc useful mineral pro::!ucts which play an iIllpOl"t<:lnt
part as fillers of asphalt, rubber and roofing materials, as components of
ceramics, 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. Through
th~se multitudinous uses thousands of human subjects com~ 'into contact ~ith
talc and tremol~te for every employee contributing to their production. Ar.er-
ica produces and uses more than one-third of the ~orld production. It is dif-
ficult" to imagine hOl,)' modern civilization can be sustained Without these use-

--
ful and relatively inexpensive minerals.

It seems fortunate, therefore, that talc <:lnd tremolite are so biolcgi-


call)" inert. There .is a mood in the United States today to eliminate 211
environmental hazards. No one can quarrel ~ith the humanitarian ideology
inspiring $uch enthusiasms. Too many hazardous materials have been haphaz-
ardly released into the ·human environment and it would be better to control
all industrial substances equally to achieve maxim~m security. Not only does
this 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:l
up the l..orks somet.here along the line. After all. the human body. and partic-
ularly the lungs. have some defenses. The lung constantly replaces itself as
part of normal existence. It would seem that·. al tho'ugh these defenses can be
o....eruhelmed through long exposure to asbestos minerals, this is not estab-
lished for taLc or tremolite in modest concentration. This fact should be
taken 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 of
talc. 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 capacity


to be formed as sheets, tubules~ ribbons, oblong crystals. needles. or fibers
instead of using the conventional mineralogical classifications of serpentines
or aophiboles or of asbest~fcrm minerals.

3. Talc ~nd tr.cmolite ~re biolgocal1:1 relatively inert substances ;lnd


thi.s contrnsts sharply with the marked path~£enicity of amosite and crocido-
lite~ 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 t
identify lars'\! numbers·of employees who have been exposed exclusively to one
or another ~incral. Many pulmonary lesions in silicate-industry employees ~
composites of multiple-dust and chemical e~posures and many of the nocuous
asents derive from sources other than the silicate industry in question.

5. Lung cancer has been definitely associated epidemiologically with


exposure to crocido1ite. There is no evidence that talc or tremolite posses
the biological propensity to induce neoplastic lesi~ns. There also is some
doubt as to the role of chrysotile in carcinogenesis. Even though SO:':'le stud
ies suggest that chrysotile may foster the deYelopment of lung cancer under
certain circumstances, other studies flatly contradict this evidence so that
the 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 not
nonnally occur ~s a consequence of exposure to asbes~os. Talc and trernolite
exposure 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. Chron.ic Berylliosis. Archiv fijr Getverbepath .und Gewerbeliyg, v. 19,


1962.

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:ng


Dust 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.

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