Document QM2MeaN67ZorpLJqpejpe3Nm6

j' C' to 1/3 M <?3 ; . to i> , - .WV** [1 '.CVif-..!./,. J.,. PTD-MT-24-1H77-72 FOREIGN TECHNOLOGY DIVISION v."'-'-. v~'{ :1V " . ' **..".. * `, ' .1 *4. k|`* ,* ' ^ '; . . . | ` . , "..'. . V-` !1-* ./ . ' ' THE CONNECTION'6^ PHYSICAL AND CHEMICAL ' -!- FEATURES OF ASBESTOS WITH THEIR v-...;.PATHOGENIC. EFFECT' ' : V *; I v-' r. ` ' f.` '' ! f'!'? ' r r. ,;. ..<' ... . ; ' .y\*yr.A^w ' -X-'' : by - 1 ' ~^ A . j. m"r\ Or /tY'w* ' <>'. - *'* S' iCAO1 .** ?>: t*t<( .. To. ;s|g.s Approved for public release; distribution unlimited. 8000 0661 20-L SCF-FA-6318 PRODUCED BY FORD c FTD-MT- JLlL-IMn -22,. EDITED MACHINE TRANSLATION PTD-MT-2^-1^77-72 THE CONNECTION OP PHYSICAL AND CHEMICAL FEATURES OF ASBESTOS WITH THEIR PATHOGENIC EFFECT By: F. M. Kogan English pages: 22 Source: Patogenez Pnevmokonlozov, Trudy a Vsesoyuznogo Simpozluraa (18-20 November 1968), Sverdlovsk, 1970, pp. 16-3!). " "'' Requester: FTD/PDTR fit This document is a SYSTRAN machine aided tranBla- tlon, post-edited for technical accuracy by: ' : R. Wallace.,........... : ... ..... V. * */ . *` ,. *' , ' * . riv.w.^* * V* .. . ' '; *r :* -1 *v-(5` , ....... Approved for public release;,.., :vr.y_-..'- , '.yd','. r f *>*.*/ ' . : THU TRANSLATION it A RENDITION OF THE ORIGL " HAL FOREIGN TEXT WITHOUT ANY ANALYTICAL OR :T editorial comment, statements or theories ADVOCATEOOR IMPLIED ARE THOSE OF THE SOURCE AND00 NOT NECESSARILY REFLECT THE POSITION OR OPINION OF THE FOREIGN TECHNOLOGY 01- i vision. . ' . ... :; > *j n ;K- ,w ... * `-I- . 5*>JfVvV?V', FTD-MT- zk?.umrii.. iff&i. ; V *1*' . /r.:,r. ' ... PREPARED BY' -' ``K ` TRANSLATION DIVISION FOREIGN TECHNOLOGY DIVISION WP.AF ft, OHIO., . ... .` . ., * Date it ro< 19 7? 8000 0662 PRODUCED BY FORD U. S. BOARD ON GEOGRAPHIC NAMES TRANSLITERATION SYSTEM ", > . ..yj,- ; ` .* . t* ' :. : 0 o'r-'ui .. 1 v*: .. . ' '* m ` * ,t, , ' A(, ' ` Block ' A* Italic Aa Transliteration A, a Block . Italic Transliteration pp pP R, r E 6 B 6 B, b cc Ce S, 6 B B V, V Tt Tm T, t rr r* 0. B yy yy U, u AA E D .. D, d E .Ye, ye; E, e* <t> XX 0* AX F, f ' Kh, kh . * )K * X we Zh, th u U z/ V Ts, ts 3 31 Z, z HS Yn Ch, ch ' MN Hy I. i IU U> Ztf w Sh, sh .-- RA Kx ft a KK Y, y K, k ' U1 U1 H "B \ ' i \ ' Shch, shch ; ` ,, . v*. ' \ :n MK n4 MM L, 1 . M, m v' 1 ' U w ' jy ' b i ' B A . . '* . HK O0 HH 00 N, n .. .. . O, 0 .. 3 * 9 . E, e K) K> B Yu, yu * n a nn P, P fl * 8 M Ya, ya . . <, . ' ' ; ' * * . .*... ` ` * *. . ' >"*7 ' *, . *.,.*a, r*r*v/:V`'.-i' S * <- *, , t * '- * f. ' . , , .. . . 7. ... .j > ' * yc initially, after vowels, and after <*, t; e, elsewhere,^, wKen written as 6 in Russian, transliterate as y8 or Bv The use of diacritical marks is preferred, but .such marks may be omitted when expediency dictates. f-rn VJ c ;vv t -ixyXM ?. '.~>**^*V***- ' " ' ' ` .^ .;, :. ; ,*'.j-V 1 " r : -.: :: Y " y '>' V4 FTD-MT-24-1477-7? 6000 0663 PRODUCED BY FORD HH< ' THE CONNECTION OF PHYSICAL AND CHEMICAL FEATURES OF ASBESTOS WITH THEIR PATHOGENIC EFFECT ?;- . . ' g. F. M. Kogan Institute of Industrial Hygiene v. and Occupational Diseases, Sverdlovsk ... '' '*' 1 ' . . ' One of the important contemporary investigators'oh the" ~; '/?problem of asbestosis, Gilson,.,the. Chairman of the' Committee ^ /KiSfi iV- If- ,::i Asbestos'Nitrtd Dancer of the International Union on the fight against cancer, has calculated (1965) that for the last 60 years . the comsumption of asbestos increased 1000 times, while the consumption of oil - this is a universally recognized condition , . V.iU of progress - increased only 50 times. . Asbestos has extensive : .. ... '.v-t'.-i application in an ever increasing number of branches of production. .. .. i . '4. !? /.-ji.. ,s-. - : 'V-'-r .v At the same time, along with quartz it is hardly possible to \ find a mineral dust capable of so serious a pathogenic effect on, the organism of workers. .In recent years there appeared a baslB vi.... i.'v'for considering asbestos'dust considerably more "harmful in view ......... of its established connection with cancer of the lungs and other , organs. : The nature of the aggressive biological effect of asbestos cannot be considered established with finality in spite of the large number of works carried out both here and abroad. FTD-MT-21J-1H77-72 *. 1 ` BOD 066* PRODUCED BY FORD . -:r MU.' . >; c O^iis considerable gap in the theory impedes the solution of such major practical problems as the standardization of asbestosbearing dust,- the individual preventive medicine and therapy of asbestosis. 1 For many years the special fibrous structure of asbestos was .. examined as the basic reason for its pathogenic eTfect. Gardner, . Cummings (1931), Mottura (1939), King et al (19^6), Behrens * (19^9), Vorwald et al (1951) and many others consider that only ' . rigid, relatively long asbestos fibers, introduced in the tissue " of the lung, cause its traumatization and, as a consequence, : ' sclerosis. '. "' Seemingly testifing in favor of such hypotheses are such facts as the more considerable fibrous changes during the intro- V /.' eduction of long filaments (15-20 v) and the insignificant changes * m. . during the introduction of particles of respirable fractions ... -(.<...7; p),..(Vorwald, 1951, Szimczikiewicz, ..Wicek, 1962;* Klosterkbtter, U'te around the place of the implantation of filaments, peribronchialarly, which is explained by the mechanical trauma of tissue during * respiratory movements.. Also given are such facts as the absence; of fibrosis in lymph nodes and the development of fibrosis under - - : according to the head physician of Canadian enterprises Cartier ; . " (19<9, 1955), a large number of patients sick with asbestosis - ftd-mt-24-1477-72 2 eooe t>86X PRODUCED BY FORT) tI c and, not Indifferent for the inhabitants of the surrounding area, the dust turned out to be in Vorwald's experiment barely fibrogenous. Uncritically going along with the indicated authors, some of our investigators asserted without proof that unlike quartz, asbestos acts mainly because of its own acicular structure and traumatization of tissue. Another group of researchers, Beger (1955), M. M. Vilenskiy (19^0), M. A. Kovnatskiy (1957), proceeded from the fact that asbestos, as any other silicate, is slowly dissolved upon contact with tissue juices, and resorbed silicic acid causes damage to pulmonary tissue with its subsequent substitution with the connective tissue. In favor of such a hypothesis such facts were advanced as the increased content of SiO? in the blood of the asbestosis patients (Emdina, V. A., 19^0, Pleshchitser, A. Ya., r-3:>V 191<B) the appearance of extrapulmonary pathological changes and finally the development of pneumoconiosis among those working ,. with non-fibrous silicates: nephellne',' olivine and others. h--` * conceived when upon routine examination those working on recovery ; of asbestos ores, 'cases of asbestosis were revealed, although, 'jy.'-'f; ,1. . in the composition of the suspended dust, the major portion Is . ' made up of particles of serpentine (average percentage of asbestos ^ vvtf-; could play a decisive role in the' genepia^pf'asbieatd^ was' set Op 1. On = ? r.~ introduction of pure'asbestos and serpentine it was established that*,''*' disregarding its granulated structure, serpentine indisputably ixjjrt fibrogenous effect. During the inhalation of air with mearj"concentration on the order of 115 mg/m^, for animals that *. '. . .. inhaled the dust of serpentine there developed an interstitial fibrosis, as in "asbestos" animals, although in the first months ` l V\`- FTD-MT-24-1^77-72. . \f . .. .... = : '' ' 3 ` 8000 0B66 PRODUCED BY FORD for the latter It was more expressed. Here It Is necessary to emphasize that we are consciously working with highly dispersed asbestos (see Table 1). Table 1. Average* dispersed composition of the dust of asbestos and serpentine. Form of dust 0-2 2-U iJ-6 6-10 10 microns microns microns mi crons microns Asbestos 79.1 15.* 2.6 1.7 1.5 Serpentine 78.9 12. H 3-3 2.1 3.3 ` * Average from 10 determinations. After 3 months the average content of hydroxyproline in the lungs, of serpentine" animals turned out to be equal to MOO pg, in "asbestos" - 7907.1; in control - 2750. However, in 9 months it was even higher than In "asbestos" (8MoB and 6616 pg respectively). .. ...--.v; 'V. i i N* One of the indisputably interesting features of chrysotile . .. asbestos is its relatively low degree of retention.in the lungs,. .. . According to Guyton (19*17), the rat inhales on the average 75' cm . .. : of air per minute.In three monthsIVfor a mean concentration,`of.^:i%>^r**ak. [dust In chamber'air equaling 115 mg/m , one rat inhales 23*1 mK*. 'and-in 9 months, -702 mg of dust/:' Meanwhile, the dust of chryBotlle-;V.^:;Tw-. : asbestos after 3 months of inhalation was in killed rats 3.M b#-'v *;.' -y. ,Wd'^aHer/5;;Wnth'^5i3;'SlVmg.,^.Por^coniparisbjv ieto'us "sayVthat the dust of serpentine identical'In compositionk- oVher conditions being , equat'l'/:w* a ' s****. r'etainei d in m* uch lar g- e`r r," quantit'iVe-***s:^ res .p; e c * t'i ve* . > .li"y 2* '! Oft ' C ' asiA ` -C. O mi* avTiBwImanf b' An oiMnos.nl an ft ff *1* ..inftnf to be equal to 9.9* while serpentine was almost *J times greater 36.7 mg. Thus, the retention of dust of chrysotile-asbestos is ... Insignificant, which apparently is connected with better^elimination^ of it*/; Wagner and Skidmore (1965) after 225 hours of exposure / ~ i.9 eoeo t>867 PRODUCED BY FORD at a concentration of 69 mg/m^ revealed on the average In the lungs of rata O.98 mg of chrysotlle-asbeBtos (at the same time, fiber glass - 8 mg) and established a three times more rapid elimination of chrysotile after the stopping of the dust. Consequently, chrysotlle-asbestos Is eliminated well, but the remaining comparatively small quantity, by virtue of the high fibrogeneous nature of the dust, Is sufficient for the development for fibrosis. The major portion of the dust Is driven out through the bronchi. The part which fell in the interstice at the level of the alveolar bronchioles is removed by the lymph flow. However, the lymphatic drainage of alveoli Is not able to remove the dust deposited in emplysematous vesicles formed in connection with the obliteration and obstruction of the alveolar passages. ... Thus the prolonged accumulation of this dust Is apparently w.:;'-.* '. * the reason for the developing process of fibrosis. .; _\have established thfttjyothifine-fibereqvasbestosjRnd J se rpent1ne^eire^capablfr^^^ftus 1 nhgg^^aaccttiivveer^ffIlodrroobsiist? Subsequently, this capability of Bhort-fibered asbestos was . 'V *;% ... '. ... . *;. ; *;, ... * 4 ^ . confirmed by Wagner (1958), Yoshlkava (i960). Holt, et. al . (196^) i: /;.->. Donna, Cappa (1967). .. : .. ?.. .. r /*:;V'> J .'VV'-'V ' -*' " * - " vU, The fact that the decisive role .JLs not played by the fibrous . . - ti ' - & : " 1967) showed that only the few filaments are introduced inside the ......... :v...... .................. -i >' -. :.v- cells of the alveolar epithelium, a fact which also does not confirm the mechanical hypothesis of the action of asbestos. ' . " 5 ,, . ... '' ... ... ` - . 5' '* .. . /*.fr'V > Vs-V !-v- 8000 086a PRODUCED BY FORD Having developed our experimental research, wo even could not. confirm the hypothesis about the chemical-toxic action of asbestos. During the analysis of the materials given by its supporters it is almost never possible to reveal the correlation between the manifestation of asbestos fibrosis and the 510^ content in individual persons. Extrapulmonary changes in other organs being ascribed to the action of resorbed SiOp are completely explained by the migration of the asbestos fibers detected, in particular, in parenchymatous organs. , On intraperitoneal Introduction of different types of asbestos (1968) we found its filaments not only in the liver and kidneys, but also in the lungs. Roe and Harlngton (1987) upon introduction subcutaneously of three forms of asbestos, into mice found fila*ments and inflammatory changes, and also swelling in the pericardium, pleural cavity, myocardium and mesenter. The fllamentB can penetrate tf^even,through the,wall of the bowels and reach^the pleura ^C(Westlake >t'al. safe ' . 1 We compared further the.solubility of the different forms of .asbestos and asbestos-bearing dust, and also serpentine and *brucite. Thus, after 15 days of contact of the dust of cbrysotile- asbestos with O.lf of Ringer's solution, the concentration of SiO? ' - in solution comprised at most 3.8 mgJf, and of anthophyllite - k. 8 mg/m^. (see appendix) "agree .V.: >r\ ! ' and Holt (1961)*,' who established the low solubility of chrysotile- . - ... . . : * i-i . 4). " .- asbestos; The corresponding index for asbestos-cement dust turned out to be equal_to.7.8 mgj^ .foxv fcremoliter7..2 jngjt. . 959T^7^^etn6st flbrogenous turned out to be the dust which 1 s least soluble. ... < - ... , C. <i<V'r'V-. ' ' - ...... 8000 0869 ji PRODUCED BY FORD with respect to SlOgf chrysotlle- and anthophyllite-asbestos. True, chrysotlle-asbestos shows relatively high solubility from magnesium, whose content In mineral Is approximately 40X. The concentration of magnesium In Ringer's solution in 1? days contact with chrysotlle-asbestos (1? mgX) was less than after contact with magnesium carbonate (22 mgX) and sovelite' (20 mgX). It seemed that detecting less than magnesium carbonate or sovellte, solubility with respect to magnesium, chrysotlle-asbestos possesses the greatest tendency to fibrosis. For example the hydroxyprol1ne content In lungs of animals in which sovellte was Introduced, turned out to be equal to 2200 ug, and after the Introduction of chrysotlle-asbestos - ^200 pg. Magnesium carbonate turned out to be virtually not fibrogenous. At the same time the dust of bruclte (MgO'H^O) possesses both high solubility with respect to magnesium and a high tendency to fibr06iS. . . . ,.'i '' " ' '' \ Thus, neither a mechanical'nor chemical hypothesis can explain ' the emergence of fibrosis with asbestosls.' : . `Material which consists of 15X asbestos and 85X calcined dolomite. 1, 7 8000 0670 PRODUCED BY FORD Fig. 1. The crystal structure of chrysoti 1 o-ast>estos (according to A. V. Fedoseev, L. P. Grigor'yeva, T. A. Makarova, 1966). OH on f f.,7 : V?>/?*-' * ,crystal of chrysotile-asbeBtos (Pig. .1). ., The closeness between lamellar and fibrous serpentine is connected with their common geological origin. However, In chrysotlle-asbestos, In connection with the !^^^orusite " .in'O [lii^^gyclhryBoil T-'IfSbeSitib '"^r^'Di'stinctly"visible tubu Structure, magnification 'V'32000. Aecorilng to j. M. - 1 :. T i. .'1 -i-i'l*Ltiuaft-WS yr '' ' ' ' "' ' ' ";. S . *:%. . ,. >' *-. ' 8000 0871 PRODUCED BY FORD .c .. .. , Specially studying the surface and colloidal properties of chrysotile, Pundsack (1955) established that it behaves in this respect much like bruclte. If in fibrogenesis the crystal structure and surface condltlons are important, then it was possible to assume that bruclte and chrysotile-asbestos should have similar 1'ibrogenlc ability. Our experiments showed that soft, fibrous, bruclte, not containing S10? mineral, is not inferior to chrysotile-asbestos in its fibrogenlc nature. And this is not only for intratracheal but also for lntraperitoneal introduction (see Figs. 3 and A). ^ ... ---w v-y. ^ Figure Jj. Fibrotic changes In the mesenter node after the . introduction of bruclte Term 6. month$, magnification about 5, > v objective *10* .. *c ` - * ... ' - ` L-:: " , The value of crystalline bonds in the mechanism of the action of asbestos we have also shown in another experiment. During * r.. ` * "V ` .. ' .. , .' . ' -` ' o 8000 6872 PRODUCED BY FORD calcination (800C) of chrysotlle-asbestos it loses water of crystallization and in its crystallographic constants it approaches olivine. Our investigations showed that in this case the flbrogenic nature of chrysotlle-asbestos decreases. .".ubseqnently, this was confirmed in the experiments of Esymczyklewi cs et al.(196?), erroneously examining calcined chrysotlle-asbestos as amorphous, and noncalcined - as crystal. In 1966 they showed that "crystalline" chrysotlle-asbestos, added to a tissue culture of the isolated lungs, absorbs considerably more oxygen than "amorphous" asbestos or fiberglass. The significance of intracrystalline structures is indicated by the different flbrogenic nature of the individual forms of asbestos. Thus, it is widely acknowledged that the highest fibro- genicity is possessed by chrysotlle-asbestos, and less by asbestos a of the group of amphibole, in particular anthophyllite. Meanwhile, the basic distinction between them is in the fact that in the particles of amphibole the atoms of metal are connected with SIO^ by double bonds, and.in chrysotlle-asbestos by.onei;bpnd, which-makes these bonds less stable. Furthermore, the weak lateral forces .. between the layers of the equally charged hydroxyl ions In the adjacent crystals of chrysotlle-asbestos facilitate the best .. mm asbestos 1 s'an 'inorganic polymer', the ;:Primary cell of which is ortho- and metasilicate m (A. B. Davydov, 2. T. Ivanov, 1961) In practicce this Ts confirmed *'* ; *** {v * . ' " beyond Question by the creation of synthetic inorganic fibrous , . . 10 ftOOO 0673 PRODUCED BY FORD I c i9 t.x i* i `rf:\ polymers of asbestos (A. D. Pedoseev et al . , 1966). Asbestos swells easily In water and slkallne solution. In consequence of which its total surface area Is lncreaso.l. As has been shown earlier, chrys it 12e-.'isbestos possesses a tubular structure, which determines the high specific surface area and a number of colloidal properties, among which we attribute special importance to adsorptive properties. Having compared the capability for adsorption of chrysotile- asbestos, serpentine, calcined chrysotile-asbestos, anthophyllite, tremolite, actinolite and magnesia-arfvedsonite, we established that the greatest capability for adsorption of ionic-molecular substances, and also albumin of the blood serum is possessed by chrysotile-asbestos, brucite and anthophyllite. Thus, after 3 days a charge of chrysotile-asbestos in 100 mg adsorbs 20-30 mg of albumin. The specific surface area of this dust turned out to 2 .. . be the greatest - 20 m /g. Asbestos easily adsorbs carbohydrates, amino acids etc. (Holzapfel, 1952)*' vv*'VS!h.. : _,j- According to contemporary ideas (K. Adamchik, 1952, Benson, . McPeftptfjjSg6(J^^upor^irragmen.t * 11 on' and "sWe 111 ng `silicates there occurs a rupture of 'internal ionic bonds and on adsorptive/activity *i 11 ;jbe*l>igher^-.* Obviouslythere, r I IS;- will be riigher `biological activity`6f such dust irrVel'atlonahlp Y 6000 08*^* ii ` PRODUCED BY FORD |^ I . to the biosubstratum. In particular the adsorption and bonding of albumin on active centers (Benson, Castle, 1958). ' The major value of the surface conditions and Its activity can be Judged from the results of several series of our experiments with asbestos-bearing dust. The asbestos content in them varied from 20 to SOf. They all, however, were distinguished by the fact that the surface area of the fiber was more or less covered by any bonding agent: polycondensed Bakellte, vulcanized rubber, hydrated cement, magnesia and calcium carbonate. Such powders are formed during the machining of asbestos-Bakelite, asbestos-rubber, asbestos-cement and sovelite articles. All these powders revealed a very moderate fibrogenic nature In spite of the increased hardness and acicular form of some of them and the increased solubility of others. . The hydroxyprollne content in animals Into which the dust of sovelite was introduced (2200 yg.) is substantially less than in those receiving a mechanical mixture of 85X magnesium carbonate and calcium and 15X chrysotile-asbestosi 1.e., in the same pro- this despite the fact that after 4 months the quantity of duBt of . Recently under our supervision there was conducted ah 1\': ^lAv^st^gatlon''of. the fibrogenic nature of faolite,' a material whioh ,'f- ^'""contains 60f anthophylllte, and as a bonding agent phenol '. - -;.wrr- 12 $000 PRODUCED BY FORD c formaldehyde resin. The histological studies of lungs of experi mental animals showed an extremely small fibrogenlcity of fnollte In comparison with anthophylllte. Nine months after the introduc tion of dust the average content of hydroxyproline turned out to be equal for "faolite" animals to 328*1, for "anthophyllite" 5763, for the controls 2375 wg (differences with controls are statis tically reliable). The average content of hydroxyproline for 1 mg of faolite dust was in this case 5 times less than for 1 mg of anthophyllite dust. Thus, the covering of the active sections of the surface by the bonding agent sharply decreases the fibrogonic potential not only of chrysotile but also of anthophyllite-asbestos. i e As is known, many silicates possess a flbrogenic ability. The especially increased fibrogenicity of chrysotlle-asbestos is . caused by its high specific surface area and weakness of the intracrystalline bonds which determine the formation of many topo- chemical centers which actively affect the biosubstratum. In l&i.?'?.'. .turn, the indicated.features,of asbestos largely are'.cause.d by^bwjti SfcftRSS .ttag&gg wlti ZgTerr/'J+i,-t'Wra- u.matifcl ng;; termine.d.iAnyWay ...... . . ... . . (> 8 mg) are 12* of the total number of particles in the lungs of those who died from asbestosis, their surface comprises more than 50* of the total surface of all particles (Landwehr,. , .. Bruckmann, 1962). Thus, better retention in the lungs and the relatively larger active specific surface area determine the higher flbrogenic ability of longer fibers. BOOO 0876 PRODUCED BY FORD The next major question in the mechanism of the action of asbestos dust is its interaction with the cells or the organism. It has been established that even the long asbestos particles are absorbed by one or several macrophages (VigMani, Pernls, 196*1). In this case the authors did not reveal substantial chanr.es in the macrophages. According to our observations in conjunction with A. A. Gerasimenko (1966), during the introduction of chrysotile- asbestos into the peritoneum of white mice the number of morpho logically changed and, probably, denatured macrophages is for certain 2 times higher than during the introduction of coal dust. There is reason to believe that the damage of macrophages can trigger a complex chain of immuniological reactions. Both our works (F. M. Kogan, A. A. Gerasimenko, 0. I. Bunimovich, 1967) and ' .observations of Z. S. Repnitskaya, 1967, N. T. Butkin and M. V. ' May, Medeka, I960, Gamblnl, 1961, etc., testify to this. However, In this article we do not analyze the immunological aspects of the problem of the action of asbestos, but only focus our attention on the fate of macrophages.... . . f;' ". . unction with ,A.:;P/ii>arinovskaya (1966) we succeeded in showing that under the effect of chrysotlle-asbestos (and to , a somdwhat lesser degree serpentine)., in twenty-four hours the . . ' growth of cells and their migration In the organ'culture of the lungs, of the human embryo is retarded. ;.V' .`examine these fibroblasts as a phase of evolution of the mac- ''liJ.iri-jtJ1'-'.* - . .. ... it.--, . .. 'rophage. In this connection we must give special attention............ to thj fact that the same Vigllanl and PerniB (196*1), denying thie' cytotoxic action of asbestos, established that in the culture of fibroblasts which contacted with asbestos, the collagen content In albumin Is 2 times higher than in controls. * .. 1*1 ' 6000 0877 PRODUCED BY FORD Once recently, the same authors (1968) again confirmed thenonconformity between the cytotoxic, hemolytic and fibrogenic proper ties of different types of asbestos. Klosterkotter (1968) also established that the decrease of lactic acid in the tissue culture which contacted with different samples of asbestos does not correspond to the fibrogenic ability of the latter. Unlike Vigilant and Pernis (1968) Schllpkotter established that the hemolytic activity of four forms of asbestos Is identical. PolyvlnylpyridlncN-oxide (PVN-O) retards the hemolytic activity of aphlbolic asbestos; however, it does not affect the activity of fibrosis. Vigilant and Pernis (1968) showed that PVN-0 and EDTA turned out to be incapable of protecting the macrophage from cytoxic action of asbestos. . ' On the other hand, in the experiments of Klosterkotter (1968) . a certain decrease in fibrosis is achieved on subcutaneous ' introduction of PVN-O. .. .. * .. - -* . ... ... , . - . ** r . . .. l .. - ,.., . . ; \ *. ! 1 ' ` v % \*. . i . In the carefully presented work of Roe and Harington (1968 .with the aid of histoehemical and enzyme methods it was shown - Wozniak (1966) . 8bow.ed^that;;t%; of dry tisBue") in the^oiilture of the isolated iungs.corresponds ... ^^ana^rioneaicl neaTMenryBot ;stOI Thus, in spite of the contradictions in the data of the .y-. various authors, It is possible to draw the conclusion that asbestos exerts a definite damaging action on macrophages by y changing their exchange and'changing the rate' of increase in ` and nature of the development of these cells. ' L" ). -..... 15 6000 0876 PRODUCED BY FORn Closely connected to the physicochemical features of asbestos and its action on a cell is, obviously, its malignant effect. An enormous number of publications In the last two decades leaves no doubt of the fact that among those who were :ubjected to the action of asbestos dust, one can observe considerably higher Indices of mortality from the cancer of the lungs, mesothelioma of the pleura, or from cancer of other organs. The social signifi cance of this question for all industrially developed countries is borne out by the fact that the International Union Against Cancer (U.I.C.C.) created the Committee "Asbestos and Cancer." The problem is found among those which Interest the World Health Organization. In our work in conjunction with S. Yu. Troltskiy and M. R. Oulevskaya it was established that mortality from cancer of the lungs for 10 years among workers in asbestos-enriching factories was 3.6 times higher than among other populations (with standardization of sex and age). Among the patients with asbestosls, cancer of the lungs was the reason for death in 9%, and cancer other than that of the lungs in 31* of the cases. Even larger concern Is caused by the reports from Canada (Cartier), ' USA (Selicoff et al', 1968;*'Cooper 'ef!a5^i96B), YuAR (Wagner, I960), Scotland (Maltr et alj , Finland (Kiviluoto. et al.), FRO (Bohllg), CSR (Navratil, 1968), etcl In recent years many investigators were able to obtain .. . .. .*' . 1 . . t . ^ ." i *.> .*!*.... * ^malignant growth - cancer, mesothelicyof -the pleura^-and.^ancerl" .^asbestos and form of the/latter Is shown (Smith et al, 1968)., J.;*ir.*. and R. Oraham showed the possibility for the development of cancer " ' " . ^of^t.he ovary upon lntraperitoneal introduction of asbestos. The possibility for migration of filaments'on through1 the^ljrmphatle :' systeiri and the formations of metastases in the lungs are shown. 16 fcbOO 0879 PRODUCED BY FORD c n o It Is especially interesting that induction of cancer is Increased with supplementary administration of stilbectrol. It is necessary to recognize that we still do not know the basic reason for the malignant action of asbestos. At the same time, based on the well-known physicochemical features of asbestos, we shall put forth a number of hypotheses which deserve, as it seems to us, a check. Many authors ascribe the carcinogenic action to chronic stlmulatlon of bronchial tissue by rigid fibers. However, it is known that only a small percentage of traumas is created by stimulus to malignant growth, relatively more solid powders of fiberglass or abradants do not possess such carcinogenic properties. Scar itself can hardly be the basic reason for malignency; indeed with silicosis, where the fibrosis is more considerable, a considerable Increase in the frequency of complications of cancer . of the lungs is not observed. At the same time, as observed by : ... us, the chronic pneumonia and the metaplasia of bronchial . lengthen its effect. v.hs`'- V-MS: !. Duringjthe. introduction of .polymers, around them there occurs . a formation of a conneetive^tiBSue^capsule, within which young . h?*- fibroblasts' and'a"thickened ^iayer^Heoiiagen develop'(Shabadj^**^:*^*"* 9f L. N., 1967). The constant presence of.metachromatic poly-'"' *'^V&.>.&i*ii^^eLCcharldea\lndic'atfeftjibh^ ^^i^^^T^^T^NPafure^6^1agen^^t^i?S^othe^1i.ami^the`proliferation fibroblasts within thecapsule leads ^to the appearance of Increasingly less differentiated atypical cell. . . . 1 .: t In accordance with the hypothesis of Prof. L. M. Shabad, 1967, .. these multiplying and infiltrated (through the capsule) fibroblasts precede sarcoma. It is possible also that during the prolonged . effect of asbestos, which i6 an inorganic polymer, there is a 37 aood 0880 PRODUCED BY FORD disorganization of the intermediate substance, development of atyplcal collagen and differentiation of fibroblasts, i.e., . processes lying at the principle of the growth. Furthermore, in the cells surrounded by growing fibrous tissue, in connection with deterioration in the conditions for existence, -these can be a selection and accumulation of more stable cell versions forming the initial tumoral rudiment (Warburg, 1956). The results of electron-microscope Investigations (Davis 1963 1968) make it possible to think about the damage by filaments of mitochondrle and the endoplasmic reticulum; it la possible that intact cells change and acquire a capability for atypical multipli cation. It is possible also to think that chrysotlle-asbestos, lnter- acting with the protein of a microphage, adsorbs and Joins those proteins which''play' a' significant role in the regulation of growth. It is possible that as an answer antibodies which destroy the W corresponding cells are formed. , As a result cells lacking growth-- regulating proteins are accumulated (0. Green;. . In the experi- -* , ments carried out in conjunction with A; P. Dorinovskoy (1965) : we focused attention on the fact that in the 'cultures..of tissues '*: ' -"* of the pulmonary embryo which was subjected to the action of '"? sN asbestos dust, the number of shared cells (78*) was reliably^^:;wx,,viv v-f- higher than in controls (i|6*). The impression was created that v" -T*' t*v: cr.e..ated that under the effect of asbestos the divisi' o n of part of . - V'. . ':the cells ,is detained at the previous phase of mitosis. Should ^ Sty " :":-v ' .. ,,>> ' 1 *<WT *5 18 8000 0&M PRODUCED BY FORD c " V`y. Si":.- . ' a \ 0 1- not one search here for the solution of the first stages of the process which was completed by the carclnogenase? if during the action of quartz dust the death of macrophages Is almost universally recognized, then during the action of asbestos their damage takes place, giving rise to an Initially atypical and then a malignant Increase. L. S. Salyamon assumes that the carcinogenic agents lower the ability to react to the subsequent damaging action. In connection with this atypical slow interstitial Inflammation develops; against the background of such an Inflammation, growths can develop. .. It is not possible to exclude the fact that in connection with its adsorptive properties, on the dust the concentration of some metabolites - endogenic carcinogens - is Increased. Such metabolites can be substances of the type of steroids either of, derivatives of tryptophane (Boyland, I960) or the blastomogenic - . . metabolites contained in urine (A. Kh. Kogan,. 1965) . \uilY,.- . ., Finally, the adsorptive, properties of asbestos can condition ^Moreover...the.'works of, L.. Mi\Shabad, L. N. Pylev, T. S. ng and holding in the organism for a prolonged period the ` "carcinogenic substance (e.g., benzopyrene), the latter are quickly removed and render no carcinogenic action. V:tV. r# '. ' . *; . .- ' FTD-MT-2 *1-1 *177-72 *1. . i . - 19 ^4)00 0&82 PRODUCED BV FORD c 0 Appendix 1. Physicochemical and fibrogenic properties of asbestos and asbestos-bearing dust. 76 llust O ws uHi>K C(j y> tu< e Vito *< -ot.>C^ -o4O4''--rtjt-iChrt rVuto* l/<ni E VO.O(M *OOco%*>4t.taeVM*iC< u fc CO +> 4KJL-9C< *M--~K*> >. i U*0-*oh'l 4Cwi#Nn ov i>iv2t (V.j ^fpH^4-C4 fac-44.") ftXr*>i f-*0 1 2 .r 4> x> r*j O--<X- 5V\cJ> >) Qr <0 re -4*>44CV-< e^*'E oVcx,-*-C> t o-o ribroccnlc abJ] Ivy mWoidth. In oxpert* exam. mchi 'ssKaa1*- 1 2.5 20 Practi ncoanlely 3,8 12.0 75 73 + 4 + 4 -1 4 4 2-Wite 3. Tremollte 2.28 1IJ 3,12 6.45 -- -- 4.8 7.2 23 96 5.6 + + + 4 4 + 1.92 6? 23 44 4. 5MalrniTegvneedzaioan- - 5. ActlnoJlte fi. F^ollte 7. Astoiurlte 6. Vulcanite !. Sovel lte ^10. Drue lte 2.7 425 -- 1.9 2,76 5.4 - 33 1.68 __ 2.24 2.5 2.45 1.6 ti 40 1*0 3.?:t i.n y.o 23 1.2 2.5 03 2.1 16.0 -- 3.0 "sltfltSl1- 2.7 10.2 8,8 1.0 100 l.l 4 4 4 4 * .' 1.52 59.7 33 Not fttu- 4 4 dled _n 6.0 .* 43 3*v.7n 4 + * < -4 6.5 74 !,f> 4 4 20.0 62 2.06 4 113 26.8 itic'i" 4 4 + 4 1.6 45,6 6,7 +4 _ there ere no working eontlngente'in the USSR. . , * *, A-*i - . Naturally, our Judgements are hypothetical. Moreover, we "ii have ! not given up hope # t..hat in the near ifiu> -t u9 r- e- ' - *in, *t: h.e' T USSR, the i'4 #v A- #LMi. 1^ ii ' .4.. Ji "...4 1 9 Koran 4>. M.. f c p .u n w c iu' o A. A.. $ y n u y 61 ill*4* -- )K. runny* ii camruipim, Ai 3, 1965, 34--39. ;+ j'.` 10. Kotao d>. M, Iponnttnft C. >0, I vAtiCKM 1> -- >K. Vm- riieiin n camrtanim. 4 IMG. 25--St. -* ``'I. ' `` " ` **' ' ^Vo';. - ' ftd-mt-21j-iH77-72 . 20 &600 008^ RQ PRODUCED BY FORD c . . :, . ' o SV. *f;. , r - L- :. .. 'OSijiPf. . 11. MtTUiixax B. C. -- Tcaucu toxa. n>y<ot. ccccmt. Jleimitrpa.'itKtiii -nncrtiryT rarxenw tpyaa it npod'kaGotexamift., /I. |904. 12. D * c ut n u c p A. H.-- PyKonnci. Csepa/t. miCTii'Tyra niriicitu xpyat M npoitoaOoACDainiA. 1947. . 13. n y hi k it ii a H. K. -- Aoiopnfitptr anrevpTtiiiiii: tCpanniir. rnr. oneuxt nu.m cn/nixtrou, Hcno/tMyuuux n xauecroc MCKTpoiuoamiHoiiiiiJt tia- Tepiia.soa (cnioaa, CTCkaoao.noKiio, ra/iuk, acCcci) M , 1902. 14. P c n ii ii u x a i 3. -- Autopctpcpnr anccrpr. 3<|><JiexniuiioeTi> aritmiH TyGcpkyAMS acrxitx y paGomix tiu/teaux npojKCcttfi acOccioutni npov-cv.i. Cocpa.ioBCK, 1965. 15. CiiKomu H H. -- Dir. rpyaa n npo4>aafi.. Si I, 1009. 16. Can a noil Jl. C. -- Tnr. ypyaa n npodunO.. 1962, 6. 28. 17. thraoecca A. Jl. h ap. ~ Uoaokiimnuo cii-iiixaTu. Ma-ao Hay. Ki, I960. M-.1. 18. 0> pa iik K. -- lb-ao CcKkcp r#r. FauGypr; 1952, ncpceoa. Ap. kn ini-ra MaxaiioGp. . 19. Suaitiia B. A. ~ C6. uttcwma rnr. tpyaa n npoduaGo-iaa. utin. J. 1940. np. 69-75, n. W. flt{tr R. J. Arch. Gew. Pathologic und Gcwcrbe Hygiene. 1933. `B VI, H. 3. 21. Ochrcni \V. Schwoix Z. Pathol. 14. 273. iu5l. 22. Denton R. E.. Cattle C. P..* Journ. Plrvs, them., v. 02 (1958), 7 p. 840. ` 23. B o y I i n d E. Aromallsrhc Ainine tlx enJogene Carcinogcnrs. Symp. Ober. Frtgen der Carcinogenese. Bert. I960. 24. C a r (i e r P. Arch, dc maladies professionnclles, 1949, 10, 6, 3%. Arch. env. Health, 1965. II, 3. 204--208. 25. Cltrk S. O., Holt P. F. Ann. occup. Hyg. v. 3, N I, 22--29. 1901, 26. Cooper el aj. Sami. Rtf. Dresden. II Jnlcrn. Konlcr. fiber die blolog. Wlrk. ilet Atbetlet. 1968. 27. bonne. Ctppe. Lt Med. del Lavoro v. 58, N I, pp. 1--21. 1967. 28. D a vi J. M. Urit. Journ. Exp. Path. 1903, v. 44. N 4. C. Sami. Pei. Dresden. II Intern. Konlcr. fiber die biolog. Wirk dcs Atbetlet, 190b. 29. Oamtint. Med. lav. 1961. v. 52. N 3. 186-190. .. 30. 0 a r d ner L. U, Cummin |> a D. Journ. ot Indualr. Hyp. XIII. 2.' 1931; v. XIII. 3. 97, 1931. . 31. Or ah am J, Graham R. Environment. Research, v. I, N 2. - 32. Ouyton. Am. Journ. Physiol.. 1047, 160. 1. 70-71. 33. Ilaringlon cl at Arch, of Env. Health, v. S. N 3, <53--<59. 1901. 34. I loll et at Journ. Path. Bad. 1964, 84, I. 1964. 35. King el al. Thorax, v. I'. N 3. 1946. 188-198. ,. . _ blol3o6g. . KWllvrklludtot lAosbecsltesa. l19S68a.mi. Ret. Dresden. II Intern. `. Konfer. Ober die >i;'i. 37. Klosterkfttter. Sami, Rel. Dresden. 11 Intern. Konfct. fiber die blolog. Wlrk. det Atbetlet. I9G8 ->4I. Me 1 et *1 IL Am. Ind. flyf; Assoc. Joum, 1964, 9S, '8,:33&^;34 - ,. n.. . . 4--2.--T4tvral1t.e.1. l__l -S--a-m---i.---R--e--l.--D--r-e--s-d--e--n-.--1--1---In--t-eerna. KRoenltcer. fiber die -C >-T. * :i! blolog. Wlrk. det Atbetlet. 1968. SaSiia!feaar.:-.4 Pundaack F, L. J. Php. v Cheat. Bi ' ........ l. 30,1>Jj S^.Wrk. det AsbealeC. 1009.''"* AM***. HiH." B I,". .InL J. Cancer. 2,.C28-S... . 4G.ScbllpkBtler. Sami. Rel. .DrtaJeit, 11 Intern. Konlcr. fiber die Wlrk. dee Aabeilea.-|6B'^^n^9^>^18v*-.vi -- v,, ip ii. Schm IIL SamL Rel. Dretdcn. II Inlem. Konlcr. Ober die blolog. * wSi5Wrt dea Aabealea. lOtH.^ 7>8e . Sbepera t). Arch. Infl; llcallh. 1955. lil-aSO-^TMT5^ 48. Sellcoll et a I. Sami. Rel. Dtcsdcn II Intern. Konlcr. fiber die bio Ion Wirk. drs Asbetles. I'JGS. ._ ' 49. Smith. SamL Ref. Dresden 11 Inlctn. Konter. Ober die blolog. Wirk. des Atbctlei. 1906, . .. . ;. -i VAri . *. '; Verltg Berlin. Heldel. N-Y. I9G7. 52. Shabad I. AUFylcv L. N., Kolesnichenko T. S. last spuoer.lanNeaetioonl athl eIndsetpitousteitionnl ofeardnonencs tor Cancer Health. I9&1. U.S.A. Imtuctiun In Lung Tis 63. St may E. Ochrona pracy, 1959. 14. 3. PTD-KT-24-iH77-72 21 eooo ose^t ' PRODUCED BY FORD  c 19CC4' S *.y *** * * ^ 111 * w 1 * * K- Womi.k H. AlcO. p.ocy N 3. 185--189. 55. S I y n f y k it* K-. W i 1eV K. Med. praoy. I9C2. 2. 85- X. M. Tlmlirtl, Skidmore. Siml. Hel. Dresden. II Intern. Konfi-r. fiber die biolop Wlrlc. del Aibcstci. 1968. 57. Warner, SMdmort. Ann. N. Y. Acad. Science*. 1965. 132. N t, 77--80. Ditcutt. 121--127. 58. Wiener. Slaubluncencrkrankimncn. Dd. .1, 9. 506--569, 1958. 59. W e 1111 k c el il. Lib. invesliL'.. 1055. If N II. ilOM-bim 60 \V i r b u r p O. Science. 1930. v. 123. u. 309. 61. Vorwld cl #1. Arc|i. Ind. JIyt. 3, j, I--13, IVS|. 62. V i C I i * n i. Ptrnl*. Sand. Hel. Dicidcn. It Intern. Konii/r. fiber die biolog. \Virk. del Aibeilei. 1958. 63. Yoihlkava. Jpuin. of Science o( Labour. 36. I960, I*." PTD-MT-2*l-l1l77-72 . .. . * 22 000 0885 PRODUCED BY FORD mciAsr.iPTnn C'itllitih DOCUMtNT CONTROL DATA -RAD *(llih, u* ! tkimti m MdMi uhwo* I. OMIINi*tTlIMN tACCTTIKVIITfVY r(CCMHfHMAMMUMHfktfMfJ Porelgn Technology Division Air Force Systems Command ________ U. S. Air Force___________ __ ! RIORT tIHl l# * mm a* tmtu NHfl (1 ,1,..,,,.^ l*u*.fnttivtoaoxt mci/oitV ci.4___h___.ci tiiont UNCLASSIFIED *. tOU* THE CONNECTION OF PHYSICAL AMD CHEMICAL FEATURES OF ASBESTOS WITH THEIR PATHOGENIC EFFECT tllCIMIl NOTH (Ttpr tlNNII W IMlMlN Translation r~A JVnORIII fWr1 ft/Ml MMJ Kogan, F.M, 0. DA Tt 1970 TBimti o *AMT NO. t*. TOTAL NO. OF AAOfl *. no. or mu 22 63 ORlliNAtOR'1 RIFORT NUMBIRHl iHWICtM. . FTD-MT-2R-11J77-72 *t. O TNI PONT1 NQ|| (Ar rO>rt NNOwi Oxl mo, N !1 i ; * T72-0B-07 It. MtTAlIVtlON ITATIMIMT Approved for public release; distribution unlimited. It. 4UDltMtNTAA* NOHI .. .. ... .. ... . 14. IPONiO *!* Mill TAAV AC TlVlTTr --r. *>,.. .. '" ` :: .'J 3 . jw*- U. tocT .... .......... " 111 Foreign Technology Division '7v Wrlp.ht-Patterson AFB, Ohio -i ' A general outline of the carcinogenic behavior of asbestos and the effeot of it and other mineral'powders in inducing 1X: '4 - ' ^.4 ee'^Nk. `' . ' ' '*' * A' v; "-5 :*;v ... V n " *. . ; r - *?.' . ^-7 . ' :* ` .... "** ry'*-V.. * DD ,'.r.,1473 ODD oBBf, 2Z iniri.AssiFiEri SRCunty CiRMltiCIliRR PRODUCED BY FORD . - UNCLASSIFIEDAKritrCUMilUiU7 Asbestos Biologic Effect cancer Pathogenesis 2<^ _DMr.i.ASSXriD. Securilr CIlMifUniM .V* 8000 &7 PRODUCED BY FORD I 0 DISTRIBUTION LIST Organi ration Nr Cys Orf> ani t Rt i on AIR FORCE DISTRIBUTION DIRECT TO RECIPIENTS EOS 5 E02? E018 E404 E408 E420 E413 E4 27 E429 zko$> AF/1NAKA AF/RDGC AF/RDC.C AEDC AFNL ADTC ESD RADC SAMSO AMD AFSC SAMSO FTD CCN res'h. NIA/PHS NIIR NIT PDT/PHE PDYA PDTR 1 1 1 2 1 1 2 I 1 1 2 2 ID 1 IS w r3i -:v., X A20S A210 6344 C04 3 CS09 CS 2 3 C523 C535 C557 CS9 1 C619 D008 D22 7 D220 K300 . POOS POSS ROSS DDC DMATC DMAAC/PDA D1A/DS-4C SUkr. chn . ABERDEEN R fi D CTR PJCATINNY ARSENAL HARRY DIAMOND LAB AVIATION SYS COM> USAIIC FSTC MIA RF.DSTONE N2SC NAVWPNSCEN ONR USA1CE (USAREUR) AEC CIA/CRS/ADD/SD ,, . NASA (ATSS-T}#3|v: .V ;* ` < .*: . 12 l 2 S I 1 3 1 1 I 7 1 1 2 1 1 2 S 2 . v;;% -. / - 'f ~ -4 OTHER GOVERNMENT AGENCIES ' PRODUCED BY FORD