Document Jrm0bdodgZJ4jkyDLkYJp69x2

FILE NAME: Ford (FD) DATE: 1966 DOC#: FD043 DOCUMENT DESCRIPTION: Report - Asbestos Bioeffects Research for Industry - Industrial Hygiene Foundation of America, Inc. INDUSTRIAL HYGIENE FOUNDATION OF AMERICA, Ine. IOEFFECTS RESEARCH OR INDUSTRY Medical Series, Bulletin No. 11 4 4 0 0 Fifth Avenue Pittsburgh. Pennsylvania 1966 8005 1492 FOREWORD During the past year, a number of industrial m a te ria ls have come under attack in public news media as a result of heightened public interest in the environ ment. The potential of such m aterials to ad v e rse ly affect the health of the general population through environmental contamination has been ra ise d . One such m a t e r i a l is a s b e s t o s . J h e r e have b een a r t i c l e s in the p r o f e s sio n al l i t e r a t u r e 1'2^ and in the lay p r e s s 3987654which p r e s e n t h ig h ly e x a g g e r a t e d view s of the nature and extent of the potential p rob lem . P ro m p t c r i t i c i s m has followed p o i n t i n g 4 to .0 erroneous interpretation of existing facts and publication of misinfor- matxon. At the sugg estion of s e v e r a l of its m e m b e r s , I n d u s t t i a l H ygiene F o u n d a tion held a meeting on J u ly 19, 1966 to s u m m a r i z e what in d u s tr y i s doing to develop information to protect the health of its em ployees and the public fro m potential environmental hazard. Such information should be of considerable value to all those responsible for planning of environmental and occupational health research , whether in industry, u n iv e rsitie s or governm ent. It is appropriate that Industrial Hygiene Foundation, a nonprofit r e s e a r c h association o: industries for advancement of health con servation in m a tter s r e lated to industry's operations, products and w astes, should a s s i s t in development of national environmental and occupational health r e s e a r c h to help insure that industry's needs are provided for at all stages of p ro g ram development. 1. T h o m s o n , J . G . and G r a v e s , W .M . " A s b e s t o s a s an U r b a n A i r Con tam in an t. " Arch. Path. 8J_:458, May 196b. 2. T h o m s o n , J . G . and G r a v e s , W .M . " A s b e s t o s i s in U rb an P o p u l a t i o n s . " JAMA 196:732-733, May 1966. 3. Anonymous. " A s b e s t o s : Awaiting ' T r i a l ' . " C h em . Week, p. 32, Sept. 10, 1966. 4. G r o s s , P. Letter to Editor "T o d ay 's P r e s s in g Q u estio n --How Safe is Urban A i r . " Arch. Path. 82:195, Aug. 1966. 5. d e T r e v i l l e , R . T . P . L e t t e r to E d i t o r . A r c h . P a th , (to b e p u b lish e d ) 6. G r o s s , P. L e tte r to E ditor. JA M A , (to be published) 7. Hackney, R. L e tte r to Editor. Chem. Week, p. 7, Oct. 8, 1966, 8. Brown, M. C. L e tter to E ditor. Ibid. 9. E dito ria l Note (following r e f s . 7 and 8). Ibid. 8005 1493 1. Subject: Sum m ary of Need and Plana for A sbestos R esearch The purpose of this session of the Industrial Hygiene Foundation M anagem ent Planning Meeting, held in the Hunt Room of the W ebster Hall Hotel on Ju ly 19, w as (1) to help develop a better concept of the asb e sto s industry's environmental and occupational health research needs and what i s being done to m e e t them and (2) to provide the U. S. Public Health Service Surgeon G eneral with a su m m ary report and any recommendations which may be developed from the meeting to aid in setting, clarifying, and reaching sound and realistic health conservation goals in the national interest. The meeting w as sponsored by the Foundation's Policy and Plan ning Committee, Those attending the meeting w ere: Name Company Bowman, H. M. Colwell, M.O. Cralley, L. J. Davison, E .K . deTreville, R. T .P . Edwards, F.H . Grant, L. B. Gross, Paul Hatch, T .F . Hazard, W.G. Minard, David Schrenk, H.H. Smith, F.W . Smith, K.W . Smyth, H .F . Wright, G.W . Thiokol's Reaction Motors Division Aluminum Company of America U .S. Public Health Service Davison Sand U Gravel Company Managing D irector of IHF Owens-Coming Fiberglas Corporation Pittsburgh Plate G lass Company Director of IHF Research Laboratory University of Pittsburgh Owens-Illinois G lass Company University of Pittsburgh Secretary , IHF Board of Trustees Mine Safety Appliances Company Johns-Manville Corporation Mellon Institute St. Luke's Hospital T- 8005 H94 2. M r. Bowman opened the m eetin g and ask e d D r. d e T r e v ilie to conduct the s e s s i o n on A s b e s t o s . D r. d e T r e v i l ie , who had a s k e d s e v e r a l of those present to be prepared to d isc u ss their a r e a s of s p e c ia l in terest and re se arc h n e e d s , f i r s t c a lle d on D r. G e o r g e W. W right to r e p o r t b r i e f l y on h i s a c t i v i t i e s of the past year in behalf of the Quebec A s b e s to s Mining A ss o c ia tio n (QAMA), Dr. Wright said that he had been a w a re of in d u str y 's in te r e st in a s b e s to s since about 1940, a s a resu lt of his work at S a ra n a c L a b o r a to ry for QAMA. At that time no question was raise d concerning p o ssib le m alignancy. At a meeting in Antigua in 1965, QAMA exp re sse d its intention to learn, "What i s known, what we need to know, and what is unknown" con cern in g the b io e ffe c ts of a s b e s t o s . Concerning what is known. D r. Wright listed the following scientists who w ere present in Antigua: Dr. John Beattie Cambridge, England Dr. John C. Gilson Penarth, Glamorgan, Wales D r. H. Bohlig L denscheid, W. G e rm an y Dr, Roger Grainger A sbestos, Quebec Dr. Paul Cartier Thetford Mines, Quebec Dr. Pernand Gregoire Montreal, Quebec Dr. A. Claass Luxembourg, Belgium Dr. Paul Gross Pittsburgh, Pa. Dr. L. J. Cralley Cincinnati, Ohio Dr. Roland Guy C artierville, Quebec Dr. A. J. deVilliers Ottawa, Ontario Prof. A. Houberechts Hasselt, Belgium 8005 1495 3. Dr. J. C. McDonald Montreal, Quebec Dr. Arthur J . Vorwald Detroit, Michigan Dr. Leo Noro Helsinki, Finland Dr. J. C. Wagner Penarth, Glamorgan, Wales Dr. Sherman S. Pinto Tacoma, Washington D r. G e o r g e W. Wright Cleveland, Ohio Prof. Paul Sadoul Nancy, France Dr. Philip Enterline Montreal, Quebec D r . K. W. Sm ith New York, New York Dr. Philippe Duval Noranda, Quebec Dr. J. A. Vidal Montreal, Quebec Dr. Eugene Pendergrass Philadelphia, Pa. Prof. E. C. Vigliani Milan, Italy M r . K. W. N e lso n Salt Lake City, Utah In the c o u r se of the QAMA Meeting, much of "what is known" was review ed and d i s c u s s e d . D r. Wright found the meeting very valuable from a perso na l standpoint, chiefly reg ard in g d iscu ssio n s of the very pertinent q u e stio n s,"What we need to know" and "what is unknown." F o r exam ple, he stated that the word " a s b e s t o s " is as gen eral a term as " b a c t e r i a " and that it is not p o ssib le to tran slate data from one type to another. The types v a ry with origin and chem ical composition and alm ost n e v e r e x i s t in a " p u r e " f o r m . It is v e r y difficult to c a t e g o r iz e an exposure environment because of the need to capture, identify, recognize, and quantitate the m a te r ia l we now ca ll " a s b e s t o s " . During p ro cessin g , a s b e s to s , which is not indestructible, may undergo dissolution or change in form. Is the m aterial redissem in ated identical to the original, or does it differ? Dr. Wright indicated that it had been sobering to realize the extent to which asb e sto s is distributed in various forms in the general population, 8005 1496 4. and we mutt have better knowledge of where asb etto s may come into contact with humans and better recognize any adverse bioeffects which may have resulted. D r. d e T r e v i l l e next a s k e d if D r. Kenneth W. Sm ith h ad any c o m m e n t s concerning the A sbestos Textile Institute p ro g ram . Dr. Smith related that the Asbestos Textile Institute is cooperating in an extensive investiga tion with the a s b e s t o s textile industry by the U. S. Public Health S e r v ic e under the direction of Dr. Lewis J . Cralley. The ATI has felt the impact of ad verse c riticism in the form of p r e ss r e le a se s, radio, and television appearances concerning asbestos. Aside from knowing the facts concerning the true effects of asbestos upon man, the industry m ust be increasingly concerned with preservation of its m arkets as a m a tter of su rv iv al. All the individual company can do to help solve this p r e ss in g p rob lem is to provide funds, environments, and individuals for study. The b asic research needs will have to be "fa r m e d out", but studies a r e a lre ad y being conducted on insulation w o rk e rs on the West C o a st and m the M idw est. In Canada, Johns-M anville Company i s studying a ll i n s u la tion w o rk ers who have p erm its, and this study has governm ent a p p ro v al. The ATI. as mentioned, is cooperating in an extensive survey by the U. S. Public Health Service, Division of Occupational Health. The National Insulation Manufacturers Association is vitally interested in developing in fo rm atio n to p a s s on to in su la to r e m p lo y e r g r o u p s . A s he has pointed out repeatedly. Dr. Smith fe e ls that the p r im a r y need is better definition of asb esto s exposure, especially im portant in e p i d e m i o l o g ic a l s t u d i e s . What i s an a s b e s t o s w o r k e r ? In th is r e g a r d 8005 1497 5. he said, the loose thinking concerning asb e sto s exposure was demonstrated recently in Pennsylvania when the o c c u rre n c e of m esoth eliom a in a three- y e a r old child w as attribu ted to the f a t h e r 's w ork in g in in d u str y under the union category of an a sb e sto s w ork er. A ctually, this union category title covers many individuals who have no occupational exposure to a sb esto s. At this point D r. d e T re v ille c alle d on D r. L ew is J . C ralle y to p r o vide a b rie f rep ort on U .S . Public H e a lth S e r v ic e , Division of Occupational Health plans. Dr. C ralley stated that he would like to cover briefly three areas of U .S. Public Health Service, Division of Occupational Health interest. (1) A p r o s p e c tiv e longitudinal e p id e m io lo g ic a l study is now under way in four industry exposure c a te g o r ie s: (a) A sb esto s textiles (b) A s b e s t o s fric tio n p r o d u c ts (c) A sb e sto s cem ent products (d) A s b e s t o s in su la tin g m a t e r i a l s The aim is to cover at le a st 2500 w ork ers in each category with a wide range of exposure from office to production w orker and with built-in controls. E x p o su res are being defined in detail including facto rs other than asb e sto s. In addition, the p a s t h i s t o r y of p la n ts r e g a r d i n g a s b e s t o s e x p o s u r e is being recorded in an attempt to develop re tro sp ec tiv e stud ies designed to com pli ment those of a p ro sp e c tiv e n ature. D etailed information on each worker is being developed using a questionnaire approach, which includes occupations, h o b b ie s, and s m o k in g h i s t o r y . T h e s e s t u d ie s will be c a r r i e d out o v er the 8005 1498 6. lifetim e of these individuals whether or not they stay in the in dustry. At in te r vals a follow-up will be m ade using B ureau of Old Age and S u r v iv o r 's Insurance r e c o r d s and State Department of Health death r e c o r d s from which a trend of caus es of death will be developed for each group. A designated number in each group will have periodic m edical follow-ups to e sta b lish health p r o file s . While the p r o spective study itself will require 25-30 y e a rs of w o rk ers' experience, it may be possible to recognize trends as early as 5-10 y e a rs from the tim e of the base line study. (2) Concurrently, a study w ill be m ade of the lungs of individuals in the cohorts who died of cancer. This will include complete m in eral analysis of trac e m e ta ls including nickel, cobalt, chrom ium , etc. In this re g ard , individuals will be categorized into two groups-- those having significant exposure before mid 1940 and those entering exposure after this period. Tech nology has changed markedly since the 1930', and contaminant fines of asbestos have been reduced 30% or m ore. E xposure of w o rk e rs is generally no longer m a ssiv e . Data collected should help provide insight in understanding past and present worker health experience. (3) The U. S. Public Health S e rv ic e i s a ls o very in te re sted in identi fying the various types of pulmonary ferruginous bodies that have been observed in a number of persons coming to autopsy in hospitals in urban a r e a s . F o r exam p le , talc has been found to contain about 10% f i b e r s . In veiw of the w id e spread use of talc in cosm etics, e t c . , could som e of the ferruginous bodies be from this source? Also, just what does the presence of these bodies mean'' A U .S. Public Health Service records study begun by D r. Philip Enter line is designed to detect contrasting differences in trends in c a u s e s of death of w orkers in different a sb e sto s product cohorts. The importance of K nox's and 8005 1499 Doll' tudy i that early data indicate that industrial hygiene control of dust exposures will reduce the incidence of lung can cer in asb e sto s w orkers. Dr, deTreville then requested Dr. G ross to provide a detailed d e s cription of IHF' Fibrous Dust R esearch Proposal. D r . G r o s s s a id that T h o m s o n ^ ) h as found that about 30% of the people that had died in hospitals in Capetown (500 consecutive autopsies) had " a s b e s t o s b o d ie s" in the lungs. The sam e au th o r^ ) had found a sim ila r prevalence of " a s b e s t o s b o d ie s" am ong the hospital deaths in Miami, Florida. Cauna, Totten and G r o s s i ) exam ined the lungs of 100 non-selected hospital deaths for which autopsy p e r m issio n had been obtained and found that 40% of these had "asb esto s bodies" in their lungs. Ian W e b s te r ^ recently reported a 47% prevalence in Johannesburg. There is, at present, a reasonable doubt that "asb esto s bodies" are specific indicators of the inhalation of a sb e sto s fib e rs. Such bodies have been found in coal m in ers and talc w ork ers where they have been called (1) Thomson, J . G . , et al. A s b e s to s a s Modern Urban H azard. S. Air. Med. J . 7:77-81, 1963. (2) Thom son, J . G . , et a l. A s b e s t o s a s an U rban A ir Contaminant. Arch P a th o l. 8_1_:458-464, M ay 1966. (3) Cauna, D zidra; Totten, Robert S. ; and G r o s s, Paul. A sbestos Bodies in Human Dungs at A u top sy . JA M A 192:371-373. May 3, 1965. (4) W ebster, Ian. R eport of p r o g r e s s quoted in the Annual Report of the Pneumoconiosis R esearch Unit of the South African Council for Scientific and Industrial Research, 1965. 8005 1500 8. "pseudo-asbestos b o d ies." Recently D a v i s ^ and C o l l e t ^ have demonstrated the in tracellu lar development of "a sb e s to s b o d ie s" s e c o n d a r y to am orphous m aterial. A sbestos occupies an anomalous position in its ability to produce lung dam age, causing diffuse fibrosis and possibly also lung can cer. It is an om a lous inasmuch as no other silicate has been shown to p o s s e s s this ability. The fib ro sis encountered in talcosis is lim ited to the trem olite variety , which is a s b e s t o s - l i k e . On the other hand, the p n e u m o c o n io s is a s s o c i a t e d with the mining of m ic a (another silicate) has not been investigated exp erim en tally , and the fibrogenic activity of the dusts coexisting with the m i c a has not been evaluated. Other silicates may evoke either minimal or relatively slight inflammatory changes, and are incapable of producing lung cancer. Inasmuch as certain polycyclic hydrocarbons and tra c e m e ta ls known to be potent cancer-producing agents have been dem o n strated in a s b e s t o s , p a rticu la rly nickel, chrom ium and benzopyrene, the p o ssib ility e x is t s that the trac e m etals and/or the polycyclic hydrocarbons m ay be solely respo nsib le for the observed pathogenicity. This p o ssib ilit y is supported by two findings: 1. The report of Braun and T r u a n ^ which indicated that the p r e v a lence of lung cancer among Canadian a sb e sto s m in ers was no g r e a t e r than that of the gen eral population. This was in contrast to the rep ort of D o l l ^ (5) D av is, J . M . G . E lec tro n -M ic ro sco p e Studies of A s b e s t o s i s in Man and Anim als. Ann. N. Y . Acad. Scie. 132:98-111, 1965. (6) C o lle t, A. P e r s o n a l C om m unication, 1965. (7) B r a u n , Daniel C. and T r u an , T . David. An E p id e m io lo g ic a l Study of Dung Cancer in A sb estos M iners. AMA Arch. Ind. Health 0 : 6 3 4 - 6 5 3 , June 1958. (8) D oll, R. M ortality fro m Dung C a n c e r in A s b e s t o s V fo rk ers. B r i t . J . Ind. Health 12:81. 1955. . 8005 1501 9. which indicated a greatly in creased r is k of lung can cer among B ritish workers exposed to a sb e sto s dust while fab ricatin g the a s b e s t o s . 2. In a re ce n t investigation in the la b o r a t o r y of the In dustrial Hygiene Fou ndation, lung c a n c e r s w ere found in r a t s e x p o s e d for 18 months to high concentrations of ch ry so tile d u s t . ^ B e c a u se r a t s exposed to chrysotile dust by other in vestigators failed to develop lung c a n c e r , there is a good probability that the chrysotile dust that produced lung c an c e r w as sign ifican tly different from that which did not have this effect. It is p o s s i b le that this difference is caused by a coating of nickel steel alloy applied to the a sb e sto s dust particles during the continuous h a m m e r m illin g p r o c e s s u s e d fo r r e n d e r in g the dust resp irab le. This method has not been used by previous investigators. Nickel has been found capable of producing lung cancer in trace amounts. Although a sb e sto s and g la s s a r e both s i l i c a t e s , the industrial health e x p erien ce with w o r k e r s of these two m a t e r i a l s h a s been v a st ly different. No p ulm o n ary d i s e a s e h a s been r e p o r t e d in w o r k e r s e x p o se d to g l a s s dust. N e v e rth e le ss, the dust of filamentous g l a s s has been labeled as highly dangerous in the lay p r e s s by a s s o c ia t io n with a s b e s t o s . It is a fact that although the effect of flake g l a s s d u st on the lungs of a n im a ls has been reported, no s i m i l a r study has been m ade of the du st of fila m e n to u s g l a s s which does not have an a s s o c i a t e d r e s i n or f i l l e r . It is proposed to exam ine the re sp o n se of a n im a ls' lungs to different inorganic fibrous m a t e r i a l s of c o n tr a s tin g c h e m ic a l c o m p o sitio n , and to c h a ra c te riz e the d iffe r en c e s and s i m i la r i t ie s in the r e sp o n se . (9) G r o s s , P . and d e T r e v i l l e , R . T . P . E x p e r i m e n t a l A s b e s t o s i s : Studies - on the P r o g r e s s i v e n e s s of the P u lm o n a r y F i b r o s i s .C a u se d by Ch rysotile Dust. To be published. ' 3005 1502 10. It is a lso proposed to investigate the influence of t ra c e m in e ra ls and polycyclic hydrocarbons ( i .e . , benzopyrene) asso c ia te d with chrysotile ore or the subseq uent p r o c e ss in g on the lon g-term r e s p o n s e of the lung to the dust. Another objective of this phase is to obtain definitive data on the lon g term effect of dust derived from filamentous g la s s upon the lungs. Three varieties of such glass dust will be investigated: 1. with the phenol-form aldehyde-type of binder 2. with the binders used in textiles 3. without binder In addition, a com p a ra tiv e study of the three m ain types of a sb e sto s dust (chrysotile, am osite and crocidolite) is proposed to attempt to pinpoint the c a u s e of biological a c tiv ity -- i . e . , whether due to s i l ic a t e s per s e or the a sso ciate d trace m etals or hydrocarbons. Positive findings would be a basis for identifying any possible health hazards and for suggesting specific engineering or other p r o c e ss controls to eliminate such h azards. I. The following fibrous m a teria ls will be reduced to resp irab le p a r t i c l e s i z e ( < 3 jj. ) and will be in je cted in am ounts of 3 . 5 m g . to 30 m g . as aqueous suspensions: 1. chry so tile dust (p r e p a r e d by milling in Wright m ill and with dem onstrated carcinogenic potential) 2. chrysotile dust (unmilled synthetic)* 3. aluminum nitride 4. tricalcium phosphate (filamentous) 5. fibrous glass a . with phenol-form aldehyde-type binder b. with binder used for textiles c. without binder 6. magnesium hydroxide (brucite) 7. m in eral wool 8. zinc oxide (filamentous) " * Sy n th etic c h r y so tile has been p r e p a r e d at Mellon Institu te By O r . William G ran qu ist. Electron photom icrographs show the c h a ra c te ristic tubular c ry sta ls. 8005 1503 11. These m a teria ls will be injected intratracheally into h am sters under ether anesthesia. Previous experience has demonstrated that asbestos bodies will fo rm in r e sp o n se to ch ry so tile dust within five months. The anim als will th erefore be held fo r f i x months and then killed. A s b e s t o s b od ies will be sought in lung juice a s well as in the lung t is s u e s . The lungs will be expanded with buffered form alin under a head of 10 c m . of w a t e r . B l o c k s re m o v e d f r o m these lungs will be se c ti o n e d at 6 U after paraffin impregnation. Th ese sections will be stained by different methods and photographed sequentially to provide m eans for studying more co m p letely the t is s u e re a c tio n to t h e se v a r io u s m a t e r i a l s . S e a r c h fo r the so -c alle d a sb e sto s bodies will be made using routinely stained sections, and section s stained fo r iron. In addition, unstained c le a r e d s e c tio n s will be examined under dark-field conditions for a sb e sto s bodies. The latter glow when exam ined in this manner. The difference in tissue reaction between the synthetic chrysotile dust and that which is known to be fibrogenic a s well as carcin og en ic will point to the contribution to pathogenicity m ade by one or m o r e of the various trace substances which may be a sso c ia te d with chrysotile a sb e sto s dust as a result of p rocessin g. The development of "asb esto s b o d ies," better termed Ferruginous b o d ie s, to d u s ts other than a s b e s t o s would point to the n o n - s p e c if i c ty of these str u c tu r e s and to the d e sirab ility of collecting such " a s b e s t o s bodies" from human lungs in o rd er to subject them to electron-probe an a ly sis. Such 8005 1504 12. a n a ly s is could give inform ation in r e g a r d to the c h e m ic a l m a k e -u p of the dust r e s p o n s i b l e fo r the developm en t of the F e r r u g i n o u s ( " a s b e s t o s " ) body. II. In ord er to explore the tiologie role of the va rio u s components of chrysotile a sb e sto s in the production of lung fib ro sis and lung c a n c e r, six s e r i e s of ra ts will be injected in tratrach eally with the following: 1. c h r y s o ti l e dust known to be c a r c i n o g e n i c ^ ) 2. synthetic chrysotile 3. synthetic chrysotile plus nickel 4. synthetic chrysotile plus chrome 5. synthetic chry so tile plus nickel, chrome and benzopyrene 6. nickel alone or with carbon a s c a r r ie r 7. chrome alone or with carbon as c a r r ie r 8. benzopyrene with carbon as c arrie r. T h ese ra ts will be held for two y e a rs and then killed. The lungs will be p r e p a r e d for exam ination and se c tio n s cut in the s a m e m a n n er a s in P h a s e 1. T h r e e other s e r i e s of r a t s will be injected i n t r a t r a c h e a l l y with the following dusts: 1. fila m e n tous g l a s s with p h e n o l- fo r m a ld e h y d e - ty p e b in d er 2. filamentous g la s s with the binders used for textiles 3. filamentous g la s s without binder. These an im als will also be held for two y e a rs and then killed. The lungs will be pre p are d and studied as in the preceding groups, with s p e c ia l attention to a sb e sto s bodies in lung t issu e s or juice. The number of anim als per s e r ie s will be such that there will be no doubt regardin g the s ta tis tic a l significance of the r e s u lt s . 8005 1505 13. III. B e c a u s e of the in te r e st of a num ber of com panies in biologic in vestigation s s i m i l a r to those planned for c hrysotile a s b e s t o s , but using in stead, am o site and CTOcidolite, an additional investigation is proposed to be undertaken concurrently. A s in the p r o p o s a l dealing with ch r y so tile a s b e s t o s , the purpose of this su p p le m e n tal, concurrent investigation is to attempt to pinpoint the cause of the biologic activity of all three m ain types of asb estos d u sts: whether this lies in the silicates per se , in the associated trace m etals, or in the a s s o c ia t e d h yd rocarb on s. Because neither amosite nor crocidolite is available as a pure synthetic m a t e r i a l , the investigation p r o p o se d for these two types of asbestos is n ecessarily different from that proposed for chrysotile. N e v e r t h e le ss, in ord er to make the investigation com plete, it is d esirable to include a ls o chryso tile in the new investigation since different methods are involved. I n a s m u c h a s the b iologic activity of a s b e s t o s s e e m s to have two c o m p o n e n t s : (a) i n f l a m m a t o r y -- r e s p o n s i b l e fo r a s b e s t o s i s , and (b) n e o p l a s t i c -- r e s p o n s i b l e for lung c a n c e r and m e s o th e lio m a , it is ad visable to in v estiga te both of them. This can rea d ily be a cco m p lish e d within the four year span contemplated for this investigation. In o r d e r to determ in e whether the biologic activity of asb estos r e s i d e s in the s i l ic a t e , in the a s s o c ia t e d trac e m e t a l s , or in the asso c iate d h y d r o c a r b o n s , a t t e m p t s will be m a d e to r e m o v e the t r a c e m e t a l s and the h yd rocarb on s from their re sp e c tiv e s ilic a te s and to c o m pare the biologic -activities of such "p urified" asbestos sam p les from which these associated m aterials have been removed. 8005 1506 14. As a p r ereq u isite to any biologic testing (insofar a s the lungs a r e co n cern ed ), it is n e c e s s a r y to reduce the a s b e s t o s to a r e s p ir a b le p a rt ic le s i z e . This will be done in the following m a n n er: the a m o site and c ro c id o - lite will be b a ll.m ille d and then fed into continuous h am m er m ills modified from a design by Holt and Young. The d u sts em erging from the h a m m e r m ills will be collected in electrostatic precip itators. This method h as been u sed s u c c e ssfu lly by us to redu ce chrysotile a sb e sto s to a p a rticle s i z e , 70% of which was r e sp ir a b le . A sufficient quantity of finely divided c h r y so tile dust is available for the purposes of this investigation. All three types of a s b e s t o s dust will be deprived of the gr e a ter portion or of all of their h ydrocarbon content in one of two w ays: 1. by continuous e x t ra c t io n with v a r i o u s solvents 2. by heating beyond the decomposition point of the hydrocarbons The trac e m etals will be removed from the three types of a s b e sto s d u st by treatm ent with aqua r e g ia followed by treatment with EDT A (ethylene diamine tetraacetic acid, a chelating agent). One batch of each type of a sb e sto s dust will be su b je c ted to both p r o c e d u re s, i . e . , rem oval of trace metals and removal of hydrocarbons . Accordingly, each of the three types of asbestos dust will consist of five batches, each with a different composition: 1. the unaltered dust as collected in the precipitators 2. the dust minus the hydrocarbons (heat-treated). H ere, it is anticipated that there may also have been som e change in the chem ical str u c tu r e of the a s b e s t o s through lo s s of some molecules of water of hydration. ~ (10). Holt, P . S . and Young, D. K. A D ust-Feed MechanismSuitable for Fibrou s Dust. Ann. Occ. Hyg. 2:245, 1960. 8005 1507 15. 3. the dust minus the hydrocarbons (solvent extraction). H ere, it is anticipated that the extraction m ay not be 100% com plete. 4. the dust minus trace m etals 5. the dust minus trace m e ta ls then sub jected to solvent extraction to rem ove m o st of the hydrocarbons In o r d e r to investigate the in fla m m ato ry component of the va rio u s (15) batches of a sb esto s dust, these will be injected intratrach eally into rats and h a m s te r s . The lungs of these anim als are expected to show definitive changes within one y e a r a fter the intrapulm onary introduction of the d u sts. In o r d e r to e xplore the lung c a n c e r a s p e c t of the n e o p la stic c o m ponent of the biologic activity of a sb e sto s dust, additional ra ts will be injected with the s a m e batches of dust as above and allowed to live out their liv e s. M o st of the a n im a ls, however, will have died b efore the end of the third y e a r. The other (m esotheliomatous) asp ec t of the above neoplastic c o m ponent will be investigated by injecting the IS different batches of a s b e sto s dust within the pleural cavity of rats and h am sters and allowing them to live out their liv e s . M ost of these animals will also have died before the end of the third y e a r. F o r the investigation of the in fla m m atory com ponent of a s b e s t o s d u st, a la r g e enough number of anim als will be put on t e s t to allow sam pling at intervals throughout the y ear and still have an adequate number re m a in ing to r e p r e s e n t the 12 month old l e s io n . The final rep ort covering the entire investigation will be issu e d toward the end of the fourth y e a r . This r e p o r t will p rob ab ly be in the form of se v e ra l m anu scripts suitable for publication. 8005 1508