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FILE NAME Talc TALC DATE 1979 DOC TALC163 DOCUMENT DESCRIPTION Medical Journal Article - Asbestos Fibrous Minerals and Acicular Cleavage Fragments ards Program W W Education ational Stuches ASBESTOS FIBROUS MINERALS AND ACICULAR CLEAVAGE FRAGMENTS NOMENCLATURE AND BIOLOGICAL PROPERTIES Arthur M. Langer Arthur N. Rohl Mary Snow Wolff Irving J. Selikoff Environmental Sciences Laboratory Department of Community Medicine Mount Sinai School of Medicine of the City University of New York One Gustave L. Levy Place New York New York 10029 INTRODUCTION Inorganic Agents of Disease Some mineral species are known to be agents of human disease Kasik 1970 Aponte 1970 Langer et al 1972 Ehrenreich et al 1973a Ehrenreich et al 1973b They have been identified through case reports radiographic surveys epidemiological studies involving working populations cohorts case controls prevalence and incidence surveys and corroborative animal experimentation The diseases associated with mineral dust inhalation include known clinical entities the pneumonconioses and also for some minerals malignant tumors These effects have been observed in workers engaged in mining milling and manufacturing Up until some five years ago pathogenic mineral species which had previously been identified received attention e.g. asbestos fibers of all varieties International Agency for Research on Cancer 1977 amphibole- and contaminated talcs etc. Rohl et al 1976 However recently a number of other minerals either directly or broadly related to agents of known activity have also been investigated For example single submicroscopic amphibole fibers and cleavage fragments which contaminate Lake Superior have been the subject of several studies Bowes et al 1977 Langer et al 1979 This increased interest comes about from a number of data sets viewed against an historical background Focus on Inorganic Fibers The focus on inorganic fibers in the environment has come about in large part through observations made during asbestos studies Data indicate that 1 excess disease risk may occur with asbestos fiber exposure in circumstances other than occupational e g indirect occupational bystander in shipyards and even in familial and environmental instances see Langer et al 1978 Rohl et al 1977c as source references 2 asbestos may act as a carcinogen to greatly increase an already elevated neoplastic risk e.g. bronchogenic carcinoma in cigarettesmoking asbestos workers Selikoff et al 1968 Doll 1971 Berry et al 1972 Hammond and Selikoff 1973 Such increases are apparently multiplicative suggesting possibly a synergistic interaction 3 there is widespread asbestos fiber contamination of the environment both in situations originating from specific emis- sion sources and in situations in which there is no observable fiber used The This work was supported in part by a grant from the National Institute of Environmental Health Sciences ES 00928 ET AL ence oring ald et Rohi 377b 1968 issay y was lung istries lent in et al osure ients our tos w isked r than st are came could acic or tanton which agner ivity of nologi- ulatory ted the organic jh both by its ulatory cies on in or the ASBESTOS AND FIBROUS MINERALS 3 the basis of morphology alone there has been some dispute as to the nature of the fibrous objects in these populations This issue has often been crucial as the single factor which determined the importance of a problem To properly characterize needle inorganic particulates a number of important problems must be addressed In the workplace where asbestos is known to be used and where it can be characterized by relatively simple analytical techniques problems of identification and enumeration are minor In areas more remote from point sources where the origin of the material is unknown problematical or may consist of complex mineral mixtures the difficulties involving identification and enumeration are enormous These problems have been the subjects of three recent symposia Asher and McGrath 1978 Russell and Hutchings 1978 Gravatt et al 1978 THE NATURE OF MINERAL CLEAVAGE FRAGMENTS FIBERS ASBESTOS FIBERS AND The difficulties encountered in monitoring the environment for fibers are in part related to analytical techniques complexity of sample knowledge of source etc. However even if the mineral identity of the fibrous particle is known another major problem arises nomenclature How does the investigator describe single isolated fibers whose provenance is unknown There has been a general lack of consistency in nomenclature which has led to confusion so that important environmental issues have been obscured by differences in terminology e.g. fibers have been called asbestos which may not have been asbestos and fibers have been called acicular cleavage fragments which may have been asbestos These problems may be illuminated by a discussion of nomenclatural difficulties The Mineral Fiber Defined toa The mineral fiber which occurs in nature is the result of a process of crystalliza- tion This object possesses an elongate habit and may be bound by planar surfaces formed during growth called crystal faces The growth of these surfaces follows kinetic crystallographic and thermodynamic laws and the expressed faces represent those forms which survive crystallization These are generally planes of least attachment energy in that planes with the greatest attachment energy and therefore greatest growth rates tend to grow out of existence Dowty 1976a Dowty 1976b The fiber form is morphologically defined by an extremely high length.width ratio superficially resembling organic fibers such as cotton and animal hair The mineral fiber may be a single crystal or may be composed of multiple intergrowths of single crystals as in the case of asbestos Campbell et al 1977 Zoltai 1978 Thrush 1968 The mineralogical literature is replete with definitions concerning single fibers and composite strands Single crystal fibers have been described as capillary filiform acicular hair thread needle etc. Nomenclature for composites of mineral fibers is more limited with such aggregates described as fibrous aggregates of capillaries etc. etc. The term asbestiform is also widely used but specifically for aggregates of mineral fibers which possess distinct physical properties or condition asbestos a LANGER ET AL The use of the term fibrous connotes that the material originated in nature through processes of crystallization the form observed is a natural habit with each single component crystal of the aggregate bound by planes formed during growth Each of the single fiber strands posseses a high length ratio A number of mineral species may possess these characteristics including asbestos minerals The surface exhibited by these asbestos fibers may be crystal faces or possibly twin planes Langer et al 1974 Asbestos Fiber Defined Asbestos minerals occur naturally They are usually fibrous have extreme length ratios are flexible possess high tensile strength and are easily separated into filamentous strands Zoltai 1978 It is important to note that although most exploited asbestos deposits throughout the world possess these characteristics there are exceptions For example the definition does not hold for some chrysotile deposits in California which have been described as the Coalinga In these fibers occur as intergrown mats with few of the above characteristics visible or even measurable The important asbestos characteristics which distinguishes this mineral group from fibrous forming silicates are based on its condition as determined on bulk samples megascopic properties It follows that examination of single submicroscopic fibers of asbestos taken from a known specimen may not display these important characteristics Occasionally when viewed by electron beam instrumentation long amphibole asbestos fiber greater than 20 microns in length may show curvilinear form Langer 1974 However the majority of fibers appear submicroscopically to be straight rectilinear sticks Fiber tensile strength is as yet unmeasurable on this level of observation and the extrapolation of the property is by implication only Ross 1978 Using strict mineralogical nomenclature isolated submicroscopic single fibers derived from known asbestos sources could not be termed asbestos Asbestos and Amphibole Nomenclature It is important to note that asbestos fibers are considered condition variants of common silicates Leake 1978 in that they are compositional and crystallographic equivalents of their forming analogues but possess different physical properties For example the asbestos variety of the forming silicate riebeckite is crocidolite In current usage asbestiform denotes an asbestos variety of silicate fiber it may be used as a synonym for asbestos Campbell et al 1977 Zoltai 1978 Although recommended a current dictionary of geological terms suggests that asbestiform may be used to describe fibers which merely resemble asbestos Thrush 1978 Confusion of nomenclature has resulted in part by a lack of agreement among mineralogists The amphiboles themselves have recently come under close scrutiny by an International Commission Leake 1978 The recommended nomenclature for amphiboles may be used to describe asbestos and its related compounds For example when only the general nature of an amphibole is known i.e. the optical properties suggest a certain mineral species but the chemical composition is unknown then the assigned mineral name becomes an adjective which is followed by the term amphibole Therefore loosely characterized amphiboles may be ASBEST termed the apl tion th be rep sugge asbest genera precis Tt acrony terial v recomi is raise literatu Cl FC enviror specie crystall size tion of Cleava acicula especi Ch crystall are no bond s attracti minimu role in abnorn energy etc. wi 11 be thos crystal formati ment formati Be intern becom locally tions o The sa subjec For ex acicula ASBESTOS AND FIBROUS MINERALS S termed e.g. grunerite amphibole is also recommended that for asbestos where the approximate chemical nature of the mineral is known but not it precise composition the recommendations made above should be followed but amphibole should be replaced by asbestos g grunerite asbestos Precise mineralogical terms suggest that for example crocidolite may be described as ) amphibole asbestos uncertain mineral character 2 riebeckite asbestos approximate or general nature known 3 magnesio asbestos chemistry and character precisely known or asbestiform magnesio The Commission also recommends discrediting the mineral name amosite an acronym for Asbestos Mines of South Africa since the originally described material was a mixture of anthophyllite and actinolite Zoltai 1978 Although they recommend the use of either grunerite asbestos or asbestiform grunerite the caveat is raised that the term amosite is firmly ensconced in the biological and mining literature Cleavage and Cleavage Fragments Defined For the most part particle exposure in the workplace and in the general environment are to respirable comminuted objects When inorganic mineral species are comminuted rupture occurs along planes which for the large part are crystallographically predetermined and in a sense controlled Although minerals reduce through parting fracture and cleavage Langer 1979 in press reduction of minerals such as amphiboles tend to be controlled by structural elements Cleavage may be an important factor in the formation of elongate objects in that acicular cleavage fragments are frequently indistinguishable from mineral fibers especially on the submicroscopic scale Cleavage in minerals is normally defined as a planar separation occurring along crystallographic planes with the lowest surface energies These are the planes are normally parallel to planes of the greatest net density of lattice points greatest bond strength and density parallel to planes of greatest spacing interplanar attraction is small as compared to planar forces and parallel to those planes of minimum surface energy Methods of size comminution may also play a significant role in determining how minerals break For example crushing may produce abnormal cleavage planes by inducing repulsive forces on normally high surface energy planes These local areas may produce such effects as crack branching etc. which may have little relationship to the crystallographic structure It is important to note that those faces with the lowest cleavage energy tend to be those planes with the least attachment energy Therefore when one compares crystal face expression on occurring fibers one may observe that ease of formation of cleavage planes normally follow prominence of crystal face development Crystal face development is therefore a good prediction of cleavage plane formation Dowty 1976a 1976b Because cleavage is influenced by factors other than those of the order internal structure crystallographic control it follows that secondary factors may become increasingly important in some instances These secondary factors are locally controlled and may be related to local variance in crystal chemistry conditions of crystallization intergrowth with other minerals ex solution phenomena etc. The same mineral species may therefore express different resultant forms when subjected to identical comminutive forces These forms may range considerably For example tremolite may occur in nature as true asbestos may be reduced to acicular cleavage fragments or equant cleavage fragments Tremolite may there- 6 LANGER AL oe fore be observed with a range of habits and morphological varieties as a function of Ce chemistry conditions of growth etc. These morphological variations may have associated with them different disease potentials significantly different size distribution characteristics differing persistence in the environment differing inhala- tion potential etc. see discussion in Langer 1974 ee Discussion Fibers and Acicular Cleavage Fragments ~e Several recent papers have presented excellent reviews concerning the terminology of mineral fiber asbestos and the importance of utilizing the correct nomenclature when describing these objects in the environment Campbell 1977 Zoltar 1978 Ross 1978 Concern is properly voiced amongst mineralogists that the improper use of mineralogical nomenclature might conceivably classify many asbestos materials as asbestos with the further concern that much of the mining industry will come under unnecessary attack because the current criteria used to identify asbestos in the environment is a catch term which may include many other substances Condition of fiber in nature as a result of growth is the only criteria for distinguishing asbestos from its forming analogues Since condition cannot be measured on single isolated submicroscopic fibers strict adherence to mineralogical terminology prohibits the use of the term asbestos for any elongate amphibole encountered in the environment Distinction between crystal face and cleavage plane fiber or acicular cleavage fragment appears to be an important issue as well Yet the two planes tend to form along the same orientations Amphibole asbestos fibers tend to develop planes in nature whether twin or face development that differ from the cleavage planes of their forming analogues The question is begged does this mean the biological activities of those planes are so different that a e.g. crocidolite asbestiform 010 surface can induce mesothelioma whereas a riebeckite 110 cannot See discussion of faces and cleavage in Langer 1979 Knowledge of the properties of asbestos is crucial in an extrapolation to mineral fibers as a generic group of agents with biological potential In the best of circumstances it is difficult to use proper nomenclature without some degree of uncertainty The original federal documents which focused on problems concerning asbestos only had not considered the nuances associated with application of such a standard to other areas especially those which involved minerals which were only related or resembled asbestos Had all the variables been foreseen current problems which are correctly raised might have been avoided Yet these problems exist and should be addressed quickly Some of these center around the following variables Distinction Between Cleavage Plane and Crystal Face on Particles Observed in the Evironment Normally the internal structure of a mineral influences the external morphology or crystal face development As crystal morphology is related to internal structure so are the planes of failure cleavage planes As the high energy surfaces grow out of existence as a result of attachment energy the low energy surfaces generally remain on a crystal Cleavage occurs in planes parallel to these low energy planes Based on theoretical and observed cleavage ASE plai cry fore cle min par are terr asb are acti ing latu of 1 aci Ing ple sur Doi car wid cry fror dov bes diff are bea Ch tho the for ira the POREZN POREZN POREZN POREZN POREZN POREZN Th pro ast AL of ay Ize la- terect 77 hat any the aria nay for ibe ogi- 10k age orm Tor aloose ace of is is with hout on ited ved bles een ese Ob- ices ly is the th INE age ASBESTOS AND FIBROUS MINERALS 7 plane development the ranking of crystal faces which appear as the result of crystallization normally follows the ranking of cleavage plane development Therefore the present concern which decries the fact that minerals in the environment are cleavage planes and not crystal faces is translated into the following such minerals observed are acicular cleavage fragments and not fibers these mineral particles are from forming silicates and are not asbestos derived the minerals are not asbestos and therefore may not be active biologically Adherence to terminology indicates that if the original condition of the mineral is unknown then asbestos can't be used These caveats are indeed true However two shortcomings are obvious 1 there are no data which indicate that cleavage planes are any less active than crystal faces 2 no isolated elongate object in the environment including asbestos meets the mineralogical asbestos definition senso stricto Criticism has been leveled at regulatory agencies and their imprecise nomenclature maintaining that strict adherence to mineralogical terms will reduce problems of lumping the asbestos materials with asbestos While it is correct that an acicular cleavage fragment cannot be asbestos by definition the argument suggesting differences in biological potential between these entities is untested For example is not known to what extent cations are distributed on a cleavage plane Are the surface charges the same are cations equally distributed or are they uniform Does the asbestos property which distinguishes it from its forming analogue carry down to the single fiber level Does asbestos result from anomalous chain widths defect structures etc. Veblen 1977 or is it the result of a perfect single crystal development Zoltai in press Does asbestos commonly indistinguishable from forming silicates on the submicroscopic level carry its peculiar properties down to the submicroscopic level Although there are marked cleavage differences between the amphibole asbestos minerals and their forming amphibole analogues Ampian 1978 it is difficult to distinguish between these planes on a sublight microscopic level There are suggestions that differences in the crystallographic axis parallel to the electron beam would produce slight variations in selected area electron diffraction patterns Champness et al 1978 Nord 1978 This matter is still being investigated although it is beyond the routine analysis required by regulatory agencies enforcing the asbestos standard' Aspect Ratio There are investigators who state that the aspect ratio observed for asbestos minerals are completely different from those observed for cleavage fragments of asbestos minerals e.g. Campbell et al 1977 is alleged tnat the regulatory 3 aspect ratio for fibers is too small and includes too many ert cleavage fragments in the asbestos enumeration However some of these de- e terminations are based solely on light microscopy Selikoff 1977 and the ratios observed for standard asbestos mineral standards by electron beam instruments e n especially transmission electron microscopy includes many short fibers and their fragments The relative dimensions of standard asbestos minerals observed by electron microscopy closely parallels those defined by the federal regulations Table 2. see plates 1-3 The aspect ratio need not be the same for all fibers nor all varieties me be meee These are reports that the use of electron optical systems may be used to differentiate these forms Data yh produced by Lee et al 1978 and Champness et al 1978 indicate that 010 010 100 planes of amphibole en asbestos can be differentiated from the 110 on the basis of their characteristic SAED pattem Res ERAT LANGER ET AL. Fractions Selected Selected Asbestos Asbestos Fractions ON 601 oz Aspect Aspect is) ie] rae) Respect to 1730 238 238 6s ry 02-4 St 47.3 47.3 gt 4s 2 Q ia) G L 39 Manipulation o'St-t % gtr Manipulation Manipulation Ot 377 68.1 OLE 40h Change Change z0 6 61 t 1 0) 36.3 0.2 Suspension seconds 15 minutes minutes disrupter 40 wats COEF Ort Op SNEM African 60 Sonified 40 = Op . ON 98 git 4B Ok 8S}. 06 69 wats seIdnuip-(@9 *18}0N2S{P-189 Sonifed for Bal seconds seconds ely eee Blt s> JO 1B edt Ot ae SUONSEs4 ON uaisedng aiqesday ON ove 996 Z22 gee jo souey adsy *) ,ATOPIUD POIBVNDE-AM, :eosAuo:SwleEpisd0ID, :anOsSALYO, SIEVL sanoshug saowy ayjowas), PAL-egedePayiw-eQ Pajpw-yeg Buoyed "BUWO "SPUODESseynuiw sAjlUdS spudges 0 re9 cus 958 Seybe sBYUOS "SpUODAS spuodas lde ert i\2p (tot OD NOSE 09 OOF IE "SPURS 10) 1B IE /Bur4) 09 PayIUOS $1 SB JO} si 9s 8rc z6r 'UBOUNY 'SUBSBUPY Pa!UOS UedUyYUBS) s8u)} UINOG WINDS D WINDS YINOS BuyeoD eBuyeag DIN'DOIN *"KhQr) HDIN HIN venosAudOsowy wansowy -aysowy, sayjowas -eysowWy, syowy, Ll. ; ; . < a arhett] i2S]wo ~ we TgSwoa8&e%f4RWsEBxgxeS2vZshBcoraeplt . . ASBESTOS AND FIBROUS MINERALS My de, oye S iN ems 5 Aes: e PLATE 1. The UICC Standard Reference Amphibole Asbestos Minerals a crocidalite South Africa Kuruman area b amosite South Africa Penge area c anthophyllite Finland All fibers presented at approximately the same magnification X7000-9000 The size distribution of crocidolite both length and diameter is skewed towards the smaller dimensions more than amosite amosite is skewed more than anthophyllite see Langer et al , 1974 Trimbrell et al , 1970 for numerical data Short fibers with aspect ratios < 5 are numerous fragments are common see aspect ratio data Table 1 N' Aree eee I LANGER AL Bie MANUFAIKA PLATE 2. Range in aspect ratio of chrysotiles from different geological sources a harsh chrysatile from E the Globe Region Arizona as is b soft chrysotile fiber number 4 from the Jeffrey Pit Quebec sonified 60 sec ) c chrysotile from Coalinga California sonified 300 sec Magnifications range from about X4,000 A to X21,000 B to X40,000 C The aspect ratio for the Arizona fiber is extremely great most 100 all 101 101 The Canadian fiber may be reduced to the dimensions producing aspect ratios ranging from > 100.1 less than 5.1 The Coalinga fiber may produce clumps with ratios down to 2 Preparation technique cannot account for all of these observed differences see Table ) Sonification produced a size distribution of chrysotile which is frequently encountered in several work environ- ments e g , the environment of automotive brake maintenance and repair operation ASBESTOS AND FIBROUS MINERALS satile from . Quebec ange from nely creat ing 1 35 .to Sonifica * environ- oe ee ne ee troe ely voaes ven r PLATE 3. Chrysotile fiber in hman tissues Aspect ration of this single mineral species may range greatly from >> 100 to < 51 Rare cases may consist of almost 95 of fibers with aspect ratios of < 5 8 rh + H : a Lactae as 12 LANGER ET AL of a single fiber In addition to these differences alteration of fiber in any number of processes again superimposes new dimensionality tending to first increase and then decrease the aspect ratio dramatically Analyses of lung tissues bear this out DISCUSSION The term asbestos may be used to describe a mineral species only when its physical characteristics on the megascopic level are known the mineral fiber possesses tensile strength flexibility and those other characteristics which distinguishes asbestiform minerals from their forming analogues Asbestos may also be applied to submicroscopic fibers if the source materials are known for example in an asbestos textile factory where chrysotile fiber is used Such nomenclature may also be used with little disagreement if environmental sampling were carried out for example down from a known asbestos source Fibers encountered in the tissues of humans known to have been exposed to asbestos may also be so categorized Therefore it is accurate and legitimate for the environmentalist to use specific nomenclature for submicroscopic fibers if an asbestos source is established and if no interfering minerals occur in the sample Identification of such materials should be based on acquisition of morphological structural and chemical data When source materials are unknown or uncertain and morphological structural and chemical data are identical with known asbestos minerals then the terminology should be somewhat modified Investigators should state that mineral fibers are encountered which on the basis of specific criteria are identical with asbestos However the oaveat should be inserted that their absolute identity is still insecure Mineral contaminants may occur in a complex ore deposit For example both tremolite and anthophyllite fiber are encountered in commercially talc deposits If the physical characteristics of the mineral fibers are known i.e. they possess high tensile strength and are flexible then the term asbestos may be used On the submicroscopic level these physical characteristics are not measureable and the nomenclature should be modified to reflect this for example the use of the phrase identical with asbestos may be inserted as a modifier If mineral contaminants are encountered on the submicroscopic level and morphological structural and chemical data are at variance with the asbestos criteria then the more general term fiber or acicular cleavage fragment should be used modifying the mineral name MINERAL PROPERTIES IMPLICATED IN BIOLOGICAL ACTIVITY Information available about the activity of asbestos permits limited extrapolation to other types of inorganic fibers considered as a generic group of compounds The subject has been reviewed extensively and in some instances extrapolation has been attempted Langer and Wolff 1978 Stanton and Layard 1978 Allison 1973 Cooper 1978 Kotin 1978 Langer al 1978 Nicholson et al , 1978 There are a number of interesting observations made in asbestos studies which are of importance to all mineral particulates ET AL umber of ase and this out when its eral fiber n disting- may also example onmental s source posed to ate for the if an as- S7 101 vle al cal structhen the at mineral itical with ntity is still nple both d talc de.e they y be used asureable use of the contaminstructural re general je mineral Y extrapola- up of com- instances nd ard lso Ital los studies ASBESTOS AND FIBROUS MINERALS 13 Fiber Length Theory and observation suggest that fibers less than 5 microns length may be completely phagocytosed in vivo whereas those greater than 25 microns are generally not Allison 1973 Intermediate size fibers especially those near 20 microns in length may be only partially phagocytosed or may cause thinning of the phagosomal membrane and may in alveolar macrophages cause lysosomal enzymes to leak into the cell's cytoplasm This inability to completely engulf long fiber has been called frustrated phagocytosis Kuschner and Wright 1976 Long fibers may be responsible for cell death and the sequelae leading to parenchymal scarring intermediate fiber lengths may also cause cell death short fiber although phagocytosed tends to remain in the parenchyma There are extensive data to indicate that the shorter than 5 micron length fiber is by far the predominant fiber found n lung parenchyma Langer et al 1971 Langer et al 1973 Pooley et al 1970 Pooley 1972 This is also the case for human extrapulmonary organs Langer 1974 Short fiber has been observed to translocate more easily than long fiber in experimental animals Morgan 1979 In human cases of asbestosis the peribronchiolar and perivascular lesions which often accompany the interstitial scarring contain long fibers and classical asbestos bodies Yet even in these lesions short fiber invariably accompanies long fibers Septal scarring may also occur between the capillary wall and the alveolar space It is often found without significant numbers of fibers or bodies visible by light microscopy Sebastien 1978 Short fiber is implicated in the etiology of this lesion Short fiber may also be phagocytosed by attached epithelial cells Suzuki and Churg 1969 thereby gaining entrance into one of the target cells which may transform bronchogenic carcinoma Another aspect of activity recently considered is the interaction of short and long fiber in concert To summarize data exist suggesting that both short < 5 mand long > 5 ...mfiber are biologically active Some investigators consider that one size may be more important than the other in terms of fibrogenesis and carcinogenesis Webster 1969 Pott 1978 Yet extrapolation to fibers in the environment would suggest that at present all fiber lengths are suspect in producing human disease Also if fiber length is indeed important then e.g. the amphibole asbestos fibers would possess different disease potentials Crocidolite produces the shortest fiber which in South Africa has been found to be capable of producing far more mesotheliomas than e.g. amosite see length distributions Langer et al 1974 Fiber Diameter im se On the basis of data obtained in animal experiments diameter appears to play a Oe role in the activity of asbestos fiber The important diameters range from 2.5 es microns down to 0.5 microns see discussion in Pott 1978 The importance of these Sho dimensions may be underscored by the fact that almost all respirable asbestos fiber IEP certainly the amphiboles occurs with diameters less than 2.5 microns greater than ee 99 by number Langer et al 1974 Pooley et al 1970 Timbrell et al 1970 po ne Fiber diameter tends to correlate with other important parameters i.e. particle an number and total exposed surface area Correlation of these parameters with HERES activity tends to negate the simple influence of a mass factor the common units ara used in classical toxicology in determining magnitude of response Thick and long fibers constituting a mass toxin tend to produce less resonse when compared to an identical mass composed of thin fibers Diameter EY Ae in geRVs at 14 LANGER ET AL reduction reflects an increase in particle number and surface area per unit mass of material Extrapolation to fibers in the environment suggests that any diameter less than several microns should be considered to be in the active size range Small diameter fibers should be considered potentially active especially in terms of carcinogenicity Since these fibers are submicroscopic they may be visualized and enumerated only by electron beam instruments Fiber Number It is widely accepted that for two equivalent masses of mineral material if chemical parameters are also identical the specimen with the greatest number of particles tends to be the most active It has been suggested that the initiation of cell transformation appears to require a finite number of particles in contact with a specific number of target cells for a specified period of time Each animal type and fiber type appears to have its own set of conditions and requirements As an example in the rat intraperitoneal tissues require at least 10" fibers of asbestos where the potency of the fiber is strong for mesothelioma induction Pott 1978 The tumor rate incidence is directly related to fiber number in this model Fiber number reflects dose in that it represents the number of fiber hits per cell It reflects in part a possible threshold but only if time is neglected Size reduction and increase in particle number per unit mass have been shown to improve reaction kinetics in chemical systems For minerals in experimental systems in which the activity of the particle is being determined size reduction may alter a number of important factors For example size comminution may be accompanied by decrease in fiber length and increase in phagocytosis potential In this instance an increase in fiber number is also accompanied by a decrease in residence time in the target organ Other characteristics which may be altered include surface properties bond character and crystallographic characteristics Langer et al 1978 Therefore increase in particle number may in some instances increase activity but in others sharply reduce activity Where fiber mass changes for fibers within a narrow size range greatly enhanced responses may be produced For example unpublished data by Dr. Charles Gold Gold 1970 indicate that the number of asbestos bodies present per unit mass of lung parenchyma correlates with degree of scarring grade of asbestosis This tends to support the observation that increased dose mass of fiber increases biological responses Yet asbestos bodies tend to form primarily on long fibers and amphibole fibers the study was conducted with light microscopic techniques No correlation was ob served for the number of bodies in lung tissues and the presence of malignant tumors Hence the concept of fiber number fiber size and activity is extraordinarily complex Absolute number and activity may not be equal for all fiber types may not be equal for all disease entities Fiber Retention size and stability When fiber reaches the terminal bronchioles and alveolar spaces of the lung parenchyma a function of size i.e. length and diameter a number of factors may influence its retention Fiber size is of first order importance in that phagocytosis is obviously controlled to a large extent by particle length Short fiber engulfed by ASBESTOS ANI macrophages fiber phagocy those which to after an exter numencally p al 1973 Po fibers are not Retentio demonstrate Suzuki and ( Morgan and I anthophyllite pattern of de observation t cal technique instilled into i asbestos acti is of prime im investigators thought to be Comparison the different Caveats sho bronchogenic stability ord calculated ca experimental dissolution ar et al 1978 tridymite support the h tive effect to period of cell appears to i resulting in Fiber Ti Fiber Particles ent and ingestec tracheobron phage respo death may hematogeno by lymphatic bodies have 1974 Altho hial tree shi Here elimin ER AL as been fibers in vs trans- Morgan ent data | Agency e eviron- Although oval from another referenountered lungs product e at the , shape ger and it hold in I organic ircinoma dman et * to peak ncer and enic caruals yet a parallel dose another Jose is he death of expodoses or xposure often 25 dose is posure re k g equal . These ASBESTOS AND FIBROUS MINERALS 17 DISCUSSION If the above factors play some role in the occurrence of human disease then the following must be considered The different amphibole asbestos fiber varieties and chrysotile from different mines or geological localities may possess different biological potentials per unit mass of fiber Since fiber length and fiber number differ markedly the delivered dose per target cell and organ will be different Each fiber may carry with it different disease potential Crocidolite with the greatest number of short fibers per unit mass of material could be said to be quickly phagocytosed and removed from the lung Yet conversely it produces marked fibrosis when compared with equivalent masses of other asbestos fiber frequent mesothelioma and no reported difference in patterns of bronchogenic carcinoma or other asbestos diseases see Davis et al 1978 for discussion Clearly fiber length cannot be the only factor in producing human disease The work of Wagner and colleagues Wagner et al 1973 indicates that equivalent masses of short fiber of crocidolite rather than long fiber produces the greatest numbers of mesotheliomas in laboratory animals This in conjunction with Pott's 1978 concept of fiber numbers required for inducing neoplastic response appears to further call attention to the importance of short fiber The same standard for all asbestos fiber varieties is a simplifiction but there are no useful data at present to suggest an alternative approach especially since each mineral species may vary from locality to locality with resultant differing size distribution All factors influencing biological activity will therefore range greatly Standards for single fibers do not reflect these variations but the complex biological potentials associated with such changes cannot be encompassed in other than an overall approach from a practical point of view CONCLUSIONS There are many reports concerning the contamination of the environment with agents introduced through human activity Among these mineral particles have figured prominently especially mineral fibers This interest stems from wide range of problems delineated in asbestos research data which has accumulated over the past seven decades Asbestos disease has been described in occupational paraoccupational environmental and familial settings Excess cancer is common in these groups and may occur in both pulmonary and pulmonary organs One of the objects commonly used as an exposure index the asbestos body Observed in the lung parenchyma of asbestos individuals they were more recently found to be present in the lung parenchyma of individuals in the general population The use of asbestos fiber is widespread and has prompted numerous studies which have focused on fiber contamination in a range of media The most commonly used fiber in North America chrysotile has been observed to be a ubiquitous environmental contaminant chrysotile has been observed to be a ubiquitous environmental contaminant Yet the use of the asbestos body as an index of exposure is hampered by the observation that other mineral fibers may form identical objects in vivo This has LANGETEAR L between alveolar surface and the capillary wall where a fibrotic response has been observed to follow Suzuki and Churg 1969 Careful electron micorscopic studies comparing sizes of asbestos fibers in lung parenchyma with those in the pleural or extrapulmonary organs shows trans- migrated fibers to be of the short lengths and diameters Langer 1974 Morgan 1979 Sebastien 1979 Most are in the submicroscopic size range Recent data suggest excess malignancies occur in some of these organs International Agency e for Research on Cancer 1977 e Fibrous particles observed as natural or introduced contaminants in the eviron- ment are not restricted in their effects to a single potential target organ Although Oe direct transport to the lung is generally the initial and most likely target removal from the lung may in a proportion indicate only translocation from one site to another ER Since short fiber translocates more readily than long fiber this fraction is preferentially mobilized These factors hold for all inorganic fibers Short fibers encountered eR the environment may therefore be expected to lodge in organs other than lungs TR eR PE Dose SY The delivered dose to an organ e.g. the lung may be measured as the product of the number of particles entrapped in the organ and their residence time at the target Dose is therefore related to factors such as size areosol stability shape penetration deposition retention resistance to degradation etc. Langer and Wolff 1978 Classical toxicological response relationships may not hold in exactly the same manner for inorganic particles as it does for metals and organic substances see above discussions The observation has been made that the risk of bronchogenic carcinoma decreases proportionately with decreased duration of fiber exposure Seidman et al 1979 in press In addition the lapsed period required for tumor incidence to peak is increased as well Data suggest a response relationship for lung cancer and asbestosis but not as clearly for mesothelioma Excess risk of bronchogenic carcinoma in asbestos workers is mostly confined to cigarette smoking individuals yet for other diseases a.g. mesothelioma epidemiological data do not reveal a parallel parallel relationship In addition to mass fiber residence time in tissue is a major factor in dose Some fiber is phagocytized and removed eliminated or translocated to another organ hence the residence time is reduced and the corresponding dose is reduced Yet some fiber persists and the residence time is prolonged until the death of the individual Thus the dose actually increases with time from onset of exposure and small fiber mass over long lapsed periods may result in high doses or exposures It is known that mesothelioma may occur in individuals with very little exposure apparently much less than occupational concentrations Many years later often 25 to 40 years without additional fiber inhalation tumors develop Here dose is effectively increased by the greatly protracted lapsed period from onset of exposure An exposure of two fibers for a year worker may result in a different risk than that for an year with an equivalent exposure other factors being equal The latter receives a greater dose due to his increased life expectancy These factors should be considered with inorganic fibers ASBESTOS DISC the following t TI fe tra m fit Crocidolite be said to produces | bestos fib bronchoge discussion disease The w equivalent greatest nu Pott's 197 appears to The sa no useful di mineral spi distribution Standardsf potentials a overall appr CONCI There a agents intrc figured prom problems de past seven occupationa these group the objects c in the lung p found to be f The use of a have focuse fiber in North mental conta chrysotile ha Yet the observation i AL of SS all of nd est ier ite 10int lly not ng 22 by ASBESTOS AND FIBROUS MINERALS 15 macrophages tend to be removed but retention is obviously enhanced for short fiber phagocytized by attached epithelial cells According to theory long fibers are those which tend to be retained Yet here again examination of human tissues even after an extensive lapsed period since last exposure demonstrates that short fiber numerically predominates in the particle population Langer et al 1971 Langer et al 1973 Pooley et al 1970 Pooley 1972 Sebastien 1978 Clearly many short fibers are not removed regardless of the time which has elapsed since last exposure Retention may also be in part related to stability of fiber in vivo It has been demonstrated that asbestos fiber chemically and physically degrades in vivo Suzuki and Churg 1969 Langer 1970 Langer et al 1972a Langer et al 1972b Morgan and Holmes 1970 The degradation of chrysotile is greatest followed by anthophyllite amosite and crocidolite in that order The factor which controls this pattern of degradation is magnesium loss from the fiber Langer et al 1972 This observation has been corroborated in many laboratories using a variety of analytical techniques e.g. tracing a daughter decay products of activated fiber instilled into laboratory animals Morgan and Holmes It is hypothesized basing asbestos activity as a solid state tumorigenic effect that resistance to degradation is of prime importance in inducting cancer Pott 1978 This appeals to a number of investigators in that amphibole tumor induction especially for mesothelioma is thought to be greatest for those chemically resistant fiber types Wright 1978 Comparison of relative mesothelioma incidences in working populations exposed to the different fiber types have been interpreted as supporting this hypothesis Caveats should be raised here this holds only for mesothelioma excess human bronchogenic carcinoma and gastrointestinal cancer do not appear to follow this stability order animal experimental data do not readily support this in that the calculated carcinogenicity index for chrysotile exceeds all other fibers in the same experimental model Wagner et al 1973 Wagner 1974 On the other hand fiber dissolution and degradation in vivo may impart the active quality to the fiber Langer et al 1978 Chrysotile proton migration magnesium leaching and silica surface tridymite may have profound biological significance There is no evidence to support the hypothesis that degradation of fiber in vivo imparts a significant protective effect to the host Although particle persistence in the host likely increases the period of cellular contact and delivered dose and persistence at the cellular level appears to induce alterations which lead to disease processes the processes resulting in in situ degradation may also produce adverse sequelae Fiber Translocation and Migration Fiber inhalation is accompanied by host response and defense Kilburn 1978 Particles entrapped on the mucosal surface of the nasopharynx may be swallowed and ingested and then eliminated Inhalation may result in particle deposition in the tracheobronchial tree or in the alveolar space where particles may initiate macrophage response or may be eliminated by the mucocilliary escalator Macrophage death may occur At any stage particles may enter the blood stream and be hematogenously distributed throughout the host and come to rest in other organs or by lymphatical transport be sequested in nodes Kilburn 1978 Asbestos fibers and bodies have been found in every extrapulmonary tissue thus far examined Langer 1974 Although phagocytosis of long fibers may be vigorous in the trancheobronchial tree short fibers in the alveolar spaces are associated with other responses Here elimination is slower and less definite Fibers may enter the interstitium te meoe, awe, we Lach Nene Nenhe ... ... ... 18 LANGER AL ... - ' . ; : . : : { i j i { i f 'i ; ; . i \ , H i | prompted several of laboratory investigators to examine the generic group of min- eral fibers other than asbestos in a number of test systems Some of these have produced malignant tumors in animals and these results have been interpreted to mean that any inorganic fiber in contact with specific target cells may be capable of inducing a neoplastic response The complexity and ramifications of the asbestos problem may be illustrated by the contamination of Lake Superior by asbestos grunerite fiber A group of mineral fibers broadly related to and in some instances indistinguishable from asbestos by electron microscopy were observed contaminating public water supplies taken from Lake Superior This problem focused attention on a number of important issues which had never previously been addressed These issues centered on the relationship of asbestos to other forming minerals both fibrous and fibrous the nomenclature of asbestos as related to mineral cleavage differences in instruments and identification methodologies used by various laboratories surface activity of minerals differentiation between crystal face and cleavage planes in terms of biological activity the significance of aspect ratio found in microscopic and submicroscopic fibers Strict adherence to mineralogical nomenclature permits the use of the terms asbestos only when the mineral occurs naturally as a fiber possesses high tensile strength and fiber flexibility Yet in all environmental and most occupational settings these characteristics are unmeasurable particularly for individual fibers Terminology should therefore be modified to accommodate these realities The biological activity of mineral surfaces including crystal faces cleavage planes and crystallographically controlled partings is under investigation Current distinctions in terminology are perhaps less important since they are not based on biological evidence Other fiber characteristics including diameter length numbers dose etc. are also currently under study Biological activity is not restricted to a particular fiber length or diameter The aspect ratio of different asbestos minerals varies systematically and is also a function of superimposed manipulation or processing The current federal use of the 3 aspect ratio appears inclusive so that most of the asbestos fragments are counted in this size range Unfortunately this tends to incorporate much asbestos mineral into the asbestos category The study of fibers other than asbestos should be intensified i |I t | 1 t t REFERENCES : H Allison AC AC Experimental methods - cell and tissue culture effects of asbestos particles on macro- , phages mesothelial cells and fibroblasts In Biological Effects of Asbestos IARC Sci Pub 8 ' Bogovski P , Gilson JC , Wagner JC and Timbrell V , Eds , Geneva 89-93 1973 Ampian SG Asbestos minerals and their asbestos analogs In Electron Microscopy of Microfibers Off 1 Asher I.M and McGrath PP Eds U.S Govt Printing , Wash DC , 12-27 1978 Aponte G.E Pneumoconioses pathologic considerations In 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Mackler A.D and Pooley F D Electron microscopical investigation of asbestos fibers Environ Health Persp , 9.63-80 9.63-80 1974 Langer A M. Maggiore C.J. Nicholson W.J , Rohl A.N , Rubin I.B. and Selikoff I .: The contamination of Lake Superior with amphibole gangue minerals in Biological Effects of Asbestos Selikoff I.J. Ed Ann N.Y. Acad Sci 1979in press Langer A.M. Rubin I.B and Selikoff I.J : Electron microprobe analysis of asbestos bodies in Proc Inti Conf Pneumoconiosis Johannesburg 1969 Shapiro H.A , Ed Oxford Univ Press N.Y , p 57-69 1970 Langer A M. Rubin I.B. and Selikoff 1 .: Chemical characterization of asbestos body cores by electron microprobe analysis J. Histo Cyto , 20. 723-734 1972a Langer A.M. Rubin 1.8 , Selikoff I.J. and Pooley F D. Chemical characterization of uncoated asbestos fibers from the lungs of asbestos workers by electron microprobe analysis J Histo Cyto 20 735-740 1972b Langer AM Selikoff I.J and Sastre A : Chrysotile asbestos in the lungs of persons in New York City , Arch Environ Health 22 348-361 1971 Langer M and Wolff M .: Asbestos carcinogenesis In Inorganic and Nutritional Aspects of Cancer . Schrauzer G.N. Ed Plenum Publ Co N.Y. 29-55 1978 Langer AM Wolff MS Rohl N. and Selikoff 1.J Variation of properties of chrysotile asbestos subjected to milling J. Toxicol Environ Health 4 173-188 1978 Leake B E. Nomenclature of amphiboles Amer Mineral 63. 1023-1052 1978 Lee R.J. Laily J.S and Fisher R.M Identification and counting of mineral fragments Nat Bur Stand Sp Pub 506. Workshop on Asbestos Definitions and Measurements Gravatt C.C. LaFleur P.D. and Heinrich K , Eds , U.S. Govt Print Off , Wash DC , 387-402 1978 McDonald J.C. Becklake MR Gibbs GW McDonald A.D and Rossiter CE The health of chrysottle asbestos mine and mill workers of Quebec Arch Env Health 28. 61-68 1974 Morgan A. Fiber Dimensions Their Significance in the Deposition and Clearance of Inhaled Fibrous Dusts Dusts and Disease this issue 1979 Morgan A. and Holmes A. Neutron activation techniques in investigations of the composition and biological effects of asbestos In Proc Inti Conf Pneumoconiosis Johannesburg 1969 Shapiro HA Ed Oxford Univ Press N Y. 52-56 1970 Nicholson WJ WJ Langer A.M. and Selikoff 1 J Epidemiological evidence of asbestos Part II Extrapola- tion to other inorganic fibers in Workshop on Asbestos Definitions and Measurement methods Nat Bur Standards Sp Pub 506 Gravatt CC , LaFleur PD and Heinrich KFJ KFJ Eds Nat Bureau Standards Wash DC DC , 71-94 1978 ASBESTO Nicholson 177 Nicholson IARC S 126-130 Nicholson Congre Nicholson Inter Co NY Pr Nord Jr. G copy an Ann Arb Pooley F.C Med . 2 Pooley C Intl Cor 52-56 1 Pott F So Staub R Pott F and senscha Rohl N encount Rohl AN serpenti Rohl N 718 Rohl N spacklir Rohi AN Consum 2,255-2 Rohl N nance a Ross T properti on Asbe Eds U Russell P Occupa Arbor N Sebastien Johanne Sebastien Fibers T and Disc Seidman H observa press Selikoff I J Rept to Selikoff I J 188 22- Selikoff I.J In Proc NY 99 ET AL isk of aused Louis ons to op on CC 3 size in College 176 1. Env Quart CJ stos in . SCIS fibe aminaIJ o Intl 57-69 Jectron bestos no 20 rk City Cancer sbestos . Stand ur D ealth of Fibrous Ion and Shapiro traf ds Bureau ASBESTOS AND FIBROUS MINERALS 21 Nicholson WJ WJ Maggiore CJ CJ and Selikoff 1.J Asbestos contamination of parenteral drugs Science 177 171-173 1972 Nicholson WJ WJ and Pundsack FL Asbestos in the environment In Biological Effects of Asbestos JARC Sci Pub 8. Bogovski P , Gilson JC JC Wagner JC and Timbrell V. Eds Geneva 126-130 1973 Nicholson WJ Rohl N and Ferrand EF Air pollution in New York City In Proc 2nd Intl Clean Air Congress Englund H.M and Berry W T. Eds , Academic Press N.Y. 136-139 1971 Nicholson WJ Rohl A and Weisman I Asbestos contamination of building air supply systems In Inter Cont on Environ Sensing and Assessment 2 Las Vegas September 1975 IEEE Inc. Publ NY Pr 29-6 1976 Nord Jr. G.L. G.L. State of the analytical transmission electron microscope In Electron Microscopy and ray Applications Russell PA PA and Hutchings A E. Eds Ann Arbor Science Press Inc , Ann Arbor Mich , 133-148 1978 Pooley F.D Electron microscope charactenstics of inhaled chrysotile asbestos fiber Brit J. Indust Med . 29. 146-153 1972 Pooley F D. Oldham P.D Um C and Wagner JC JC The detection of asbestos in tissues in Proc Intl Conf Pneumoconiosis Johannesburg 1969 Shapiro H.A. Ed Oxford Univ Press N.Y. p 52-56 1970 Pott F Some aspects on the dosimetry of the carcinogenic potency of asbestos and other fibrous dusts . Staub Reinhalt Luft 38 486-490 1978 Pott F. and Friednchs K.H Tumoren der ratte nach i.p. injektion faserf^rmigerst^/ubeNaturwis- senschaften 59 318 1972 Rohl A.N Langer AM Klimentidis R. Wolff M.S. and Selikoff 1.J Asbestos content of dust encountered in brake maintenance and repair Proc Roy Soc Med 70 33-37 1077a Rohl N. Langer AM and Selikoff I .: Environmental asbestos pollution related to use of quarried serpentine rock Science 196 1219-1322 19776 Rohl N , Langer A.M. and Selikoff | J Asbestos pollution Editor Science 197716- 197716- 718 1977c Rohl A.N. Langer A.M , Se likoff I J. and Nicholson W.J. Exposure to asbestos in the use of consumer spackling patching and taping compounds Science 189 551-553 1975 Rohl N. Langer A.M Selikoff I.J. Tordini A. Klimentidis R. Bowes D.R and Skinner DL Consumer talcums and powders mineral and chemical charactenzation J Toxicol Environ Health 2 255-284 1976 Rohl N, Langer M. Wolff MS and Weisman I Asbestos exposure during brake lining mainte- nance and repair Environ Res , 12 110-128 1976 Ross M. M. The asbestos minerals Definitions description modes of formation physical and chemical properties and health risk to the mining community In Nat Bur Standards Sp Pub 506 Workshop on Asbestos Definitions and Measurement Methods Gravatt C.C. LaFleur PD PD and Heinrich K Eds U S. Govt Print Off , Wash D C. 49-64 1978 Russell P A. and Hutchings A.E. Electron Microscopy and ray Applications to Environmental and Occupational Health Analysis Proc 2nd Symp , Denver Colo 1977. Ann Arbor Sci Pub Inc. Ann Arbor Mich , 278p 1978 Sebastien P. Remarks on assessment of asbestos fiber in human tissues In Asbestos Symposium Johannesburg Glen HW | Ed Dept Mines National Inst Metallurgy Randburg 30-31 1978 Sebastien P. Janson X Riba G , Masse R. R. Bonnaud G. and Bignon J. Translocation of Asbestos Fibers Through Respiratory Tract and Gastrointestinal Traci According to Fiber Type and Size Dust and Disease this issue 1979 Seidman H. Selikoff I.J and Hammond EC Short asbestos work exposure and term observation In Selikoff I J. Editor Biological Effects of Asbestos Ann N.Y. acad Sci 1979 in press Selikoff IJ IJ : Clinical survey of chrysotile asbestos miners and millers in Baie Verte Newfoundland 1976 Rept the NIEHS 40 1977 Selikoff I.J Churg J and Hammond E.C Asbestos exposure and neoplasia J Amer Med Assn 188.22-26 188.22-26 1964 Selikoff I.J. and Hammond E C. Asbestos bodies in the New York City population in two penods of time In Proc Intl Conf Pneumoconiosis Johannesburg 1969 Shapiro HA Ed Oxford Univ Press N.Y. 99-107 1970 taney! Nowe 22 LANGER ET AL Selikoff IJ IJ Hammond EC and Churg J Asbestos exposure smoking and neoplasia J Amer Med Assn , 204 106-112 1968 Selikoff f.J. Nicholson W.J and Langer AM Asbestos air pollution Arch Environ Health 25 1-13 1972 Stanton MF and Layard M : The carcinogenicity of fibrous minerals in Nat Bur Stand Sp Pub 506 Workshop on Asbestos Definitions and Measurements Gravatt CC , LaFleur PO PO and Heinrich K. Eds U.S. Govt Print Off , Washington DC , 1-18 1978 Stanton F. and Wrench C. Mechanisms of mesothelioma induction with asbestos and fibrous glass J. Natl Cancer Inst 28 797-821 1972 Suzuki Y. and Churg J. J. Structure and the development of the asbestos body Amer J Pathol 55 79-107 1969 Thrush P W. Ed Dictionary of Mining Mineral and Related Terms US Bur Mines U.S. Dept. Int , Wash DC , 1269 . 1968 INT : Timbrell V , Pooley F.D and Wagner JC JC Characteristics of respirable asbestos fibres In Proc Intl The Conf Pneumoconiosis Johannesburg 1969 Shapiro HA , Ed Oxford Univ Press NY NY , 120-125 1970 GEee Veblen D.R. Buseck P.R. and Burnham CW Asbestiform chain silicates New minerals and structural Oe groups Science 198 359-365 1977 Wagner J.C , Berry G. Skidmore JW JW and Timbrell V. The effects of the inhalation of asbestos in rats ON Bnt J. Cancer 29.252-269 29.252-269 1974 Wagner J.C. Berry G. and Timbrell V Mesotheliomas in rats after inoculation with asbestos and other materials But J. Cancer 28 173-185 1973 knowled industry Man slag and The familiar fabrics : Nn Webster .: Unpublished addendum remarks at the 2nd Intl Conf on Pneumoconioses Johannesburg April 1969 body pa tured in Wright G. G. Are there characteristics of fibers that influence their biological effect In Electron Microscopy emphas of Microfibers Asher M. and McGrath PP PP , Eds US Govt Print Off Wash D.C. 3-11 1978 fiber for a Zoltai T. History of asbestos mineralogical terminology In Nat Bur Stand Sp Pub 506 Workshop on Asbestos Definitions and Measurement Methods Gravatt C.C. LaFleur P.D and Thi in Engl Heinrich K , Eds US Govt Print Off Wash D.C , 1-18 1978 wes Zoltar T A comparison of asbestos fibers with synthetic crystals known as whiskers In Biological en Effects of Asbestos Selikoff IJ Ed Ann NY Acad Sci 1979 in press Alexan natural by cent from 3 than sp e diameti Gl e through tion of ee differer charac meow fibrous increas } Th United ~~ bushin strand tire co dustry Fi United perfori by we NIOS C Gas Mi UY iy E 4 re r 3 at otf Sar Ping SRNR . aaaxBpiete * Seki a myNPua ee zy eee ne armen A ~ atne met me pees e ont an ae ear ene a te ne Te ate COPYRIGHT 1979 BY THE SOCIETY FOR OCCU- PATIONAL AND ENVIRONMENTAL HEALTH All rights Reserved NO PART OF THIS PUBLICATION MAY BE REPRODUCED OR TRANSMITTED IN ANY FORM BY ANY MEANS ELECTRONIC OR MECHANICALLY INCLUDING PHOTOCOPY RECORDING OR ANY INFORMATION STORAGE AND RETRIEVAL SYSTEM WITHOUT PERMISSION IN WRITING PATHOTOX PUBLISHERS INC 2405 Bond Street Park Forest South Illinois 60466 Library of Congress Catalog Card Number 79-88819 79-88819 ISBN 0-930376-08-0 Printed in The United States of America SOCIET In Decem Health Act cha in the workpla given low prior and decision w people and the protecting the t of the total envi Attempts t from newly dis surrounded the quate controls . In 1972 m met in a series From these dis Health - a mi examination of Represent from academia independent m groups The m universal dime SOEH act Through its w communicatior often different problems By p scientific and s ing to the exa occupational a With the p hopes to expar living environm By focusing pu ing the dialogu professional ar working towarc