Document daoD6ZRV1pwJe00GO31B2aqq0

FILE NAME Manville JMA DATE 1966-1968 DOC JMA213 DOCUMENT DESCRIPTION Grant Application Grant Award Letter Memo we . an an . ? > rays - . % . * Reve. De sea | . te os | re ee es . i 16324 a . s rede emf 7 tae ete at yj ne eC BOX BOX BOX tole . BOX BOX BOX uns : ie : a a aie . san . eve . rive oo te os + tee ta. os te . . . . . 237 n - hee H. Jackson te eae er tt Cg ER 1 ate Mpea cat Research Fibrous Dusts ot mT Moat, - ee submitted submitted Some asked review subject Oh timeagoyou meto a proposal on this i by aethe Industrial Hygiene Foundation to five companies After discussions . with view the Foundation staff the proposal revised to include additional dusts ar Drew, | thus broadening the scope ooff the research Another sponsor was included ooe Recently Cralley U.S.P.H.S. I met with Dr. of the Dr. Vorwald from Detroit - . and Dr. Wright from Cleveland to ascertain if they were undertaking any studies . report doing researchtherewillbe which would duplicate the proposed research in any way Happily I m able to ree* they are - that a a while ce an See no duplication *. x aye te Roe OS oes 3: . 4 4 ! . " companies Therefore recommend Manville mente "ana I strongly be a sponsinothr is that research program the and project oats! vir,esearch agreement areattached | *oe-. ane join the other copy A of s . a . * ge Mee eae f : Corning already atated Pitsburgh Pittsburgh Pittsburgh signedtheir and " Te eee Plate Olass have ms ments with the Foundation Mr. Edwards of Corning Fiberglas has atatedi ): a that his company is willing to be a sponsor Dr. Wolfsie has indicated a ="* ~ ~ oe on U. similar intent Manville part of Rubber Certain will follow the S. _ of Manville example tems a33canet oe Pe, obtained obtained a teste If be obtainedthis ". If approval can weak sponsor ce 3) details with the I.R.F. staff and representatives of some of the other taeCe af Tit : - ",, ing companies while attending another meeting in in Pittsburgh next weekae et ee? eas v ttle ee, 5 seers ne . oo . . toe" ff nee Stet. * . MB: * Stet te brew eg Ss ef aeitat# a a en . eee a gs Le TOES B ty B B de 95 Mi } B ye'tiinc73Te o factual information concerning the biological effects of asbestos peCST glass and other materials This information will be used to refute erroneous ore te ae " and misleading statemwheicnh tarse being made concerning the health hazards pees a weit ~ 4, -g associated with the use of asbeansd t reloats ed fibrous materials hazards - . wT wie ~ sa tat te . wat .. . . Lo be yy a eee as PETES rs -? a aan ce aes re > A. research laboratory proposed to study the biologie effecofttos 4 it asbestos fibers fibrous glass and related fibrous materials Substancetso "=" _-S beinvestiwig llaintcleudda naturally chrysotila amosite crocide ); i* lite synt fibh ere s st ynti hetc ic chrysotile fibrous glass asbestos fibers 20 .-.5; > known to cause canceirn animals as well as trace elements on the surfacoef ude :. S _ asbeston which may cause cancer - oo koeo . of is . ee Sponsors Sponsors ne Ps : t on ne ne oe wd ca a Manvills eet i eta 3 . eo .. 5 4, te ins Ths Pittsburgh Corning Corp. anPa is 3 ee Research Agency Pittsburgh Pa at Dr. a . TA ale OR - + rs Nyt Vee + He 8 Paul a . ws Gross ae F eo oan ew MES an gt e nee : . . . tlle te ee TE a aE . a 3 e ' . Fo a we a ee , * ae omtoen a ot ee ets n 3; . . . : nem eee a y . % iad ehity. ah et . * .e ae oo yar ^'ode, * a . to eg tee =? vcppyna-* Each sponsor will contribute 20,000.p0e0r year for years and 10,000.00 a ts: for the fourth year This cost may be reduced as the research progresse1s 2 additional companies agree to becoms sponsors Coat . Le strongly this It recommended that Hanville a sponsro esr er 34 project the present time project Approval ia requestneodw so that the program may be initiated at in once ; Personnel materials and facilities are available at . Mee. de ae ate Cc aA we tee, uf + : , a. x eh cacti. - . hn ar ant ok < <2 heey . : . 1 IS Pras tigt ce od seh ale P Ane PRAM DISET in Pad 8 Us 8 de be COPY INDUSTRIAL HYGIENE Foundation of americA INC MELLON INSTITUTE 4400 FIFTH AVENUE se PITTSBURgh PA 15213 June 3 1966 Mr. Jerry Bishop Wall Street Journal 30 Broad Street New York New York 10004 Dear Mr. Bishop With regard to my letter of May 27 the attached copies of letters from Dr. M. Davis and Dr. A. Collet agreeing with Dr. Paul Gross stand against the Thomson article on asbestos which appeared in the May 1956 issue of the Journal of Pathology may be of interest Sincerely yours deT Enclosures bcc Mr. Hugh Jackson . Robert T. P. deTreville Managing Director M.D. -- -- > iw veg C, OPY ete ee, if ve ; . a yas oe,fen ne splamay tagtit ek ie on oR! COPY MORES tarot eareerilyiss A neha eeeINDUSTRIAL HYGIENE FOUNDATION OF AMERICA INC ne MELLON INSTITUTE 4400 FIFth avenue , ai ils ghee 9 ii gesSoya tgSolas abba oe issu ae we "et yte REESfaee apheo*5o a . onal StudyPA 15213Aes PITTSSBtuUdRyG1H0 1967 cca cey Study yetetten Wall st - faee yo a Medical U. S. Rubber Company Rockefeller Center -. Americas he ae Institute ATI and "2 AsbestosTextile directly received aan n invitation to he Cherry February meeting of ATI's Board in Hill New Jersey he, Satanhae Cibring eye: 3,yagia:Peat yerletter eh ow! heysabe of Sunbury's PD will bring Mr. H. letter to the attention ofour Be | of Trustees on February 1 with the recommendation that Dr. Paul Gross | : work be continuedpendingoutcomeofATI's evaluation and decision project teedAsbestos funding of this progress iA noPur attempt to | complete Industry SAREESE of our a Certaing are : Wight Jur . INDUSTRIAL HYGIENE FOUNDATION OF AMERICA - % MELLON INSTITUTE 4400 Fifth Avenue PITTSBURGH Pa 15213 February 1967 FIBROUS DUST STUDY REPORT OF PROGRESS IN PHASES 1 & 2 July 1 1966 - December 31 1966 E es Toy . . Ferruginous Bodies from lungs of asbestos . - worker with asbestosis Ferruginous Body from aluminum silicate fiber experimentally produced in hamster lung Ferruginous Body from glass fiber experimentally_ produced in hamster lung * At the present stage of development it seems certain that results of this study will demonstrate nonspecificity of asbestos bodies and justify changing their name to ferruginous bodies from known g asbestos or unknown filamentous dusts Animals have been injected intratracheally with synthetic chrysotile dust according to the protocol Regarding Phase 3 experimental materials and equipment have been procured but purchase of animals is awaiting notification of funding If funds do not become available this phase must be set aside temporarily._ . . Spas oop. An additional aspect Phase has . . -" temporarily._ eee been added to the study Electron photomicrographic studies have been initiated with consideration of electron probe analysis also a Beli e SPONSORS Manville Corporation Corning Fiberglas Corporation Pittsburgh Corning Corporation and Pittsburgh Plate Glass Company AN ASSOCIATION OF INDUSTRIES FOR THE ADVANCEMENT OF HEALTHFUL WORKING CONDITIOI PRODUCED pes JM - 83 : aan ican la ay pMoarseesOI ead Pry esS e ei uN fe oa met toteve INDUSTRIAL HYGIENE FOUNDATION OF AMERICA AMERICA AMERICA AMERICA AMERICA ee ee ene mee MELLON INSTITUTE 4400 FIFTH AVENUE PITTSBURGH PITTSBURGH Pa 2.0 Formary ante REPORT OF PROGRESS IN PHASES | July , 1966 - December 31 1969 aN ' . . o . . - . _ $ re . . " TO... TO... . a , Ae + oy Ferruginous Bodies from lungs of asbestos . worker with asbestosis Ferruginous Body from aluminum silicate fiber experimentally produced in hamster lung Ferruginous Body from glass fiber experimentally produced in Hanister lung At the present stage of development it seems certain that results of this study will demonstrate nonspecificity of " asbestos bodies and justify justify changing their name to ferruginous bodies from known e g asbustus or unknown filamentous dusts Animals have been injected intratracheally with synthetic chrysotile dust according to the protocol Regarding Phase 3 experimental materials and equipment have procured but purchase of animals is awaiting notification of funding If do not become available this phase must be set aside temporarily beza funds An additional aspect Phase 4 has been added to thethe study photomicrographic studies have been initiated with consideration of probe analysis also Electronelectron SPONSORS Manville Corporation Corning Pittsburgh Corning Corporation and Pittsburgh FiberglaFibserglas Corporation Plate Glass Company AN ASSOCIATION OF INDUSTRIES FOR THE ADVANCEMENT OF HEALTHFUL HEALTHFUL HEALTHFUL HEALTHFUL WORKING PRODUPCEDRODUCED PRODUCED 83 Note on copy of Transactions Transactions Dr. Angevine - Please see p 111 for a picture body produced by Dr. Gross APPENDIX D of a ferruginous * RTP deT Dr. D. Murray Angevine Chief Editor Archives of Pathology . Department of Pathology University of Wisconsin School of Medicine 470 North Charter Street Madison Wisconsin 53706 March 8 1967 Dear Dr. Angevine Regarding Dr. Thomson's reply by way of review it should be re- called that the following two basic assumptions in his paper Arch Path 458 1966 were challenged | _ i. 1. that histopathologists today do not believe that the asbestos body may be nonspecific and result 2. that it is now accepted by meet that pleural plaques from inhalation of asbestos Load F x aE paper In given in October ! Dr. Paul Groas reported early findings oe, of his research on production of ferruginous bodies with asbestos fila- de mentous fibers of respirable sine Scientific questions are properly settled Ps Gross by consideration of such data not by opinions The very existence of Dr. 7 research is adequate proof that Dr. Thomson does not Gross speak for all histopathole af gists today concerning specificity of called asbestes bodies for asbestos in- i oo eee Ce ge ge Mourman's mentioned by Dr. Thomson are in accord with findings those published earlier by Dr. Kenneth Smith who said If inhalation of the asbestos fiber alone could cause pleural plaques Ppt one would expect to find * plaques wherever the fiber is used Mourman's conclusion that the dust 7 that induces the formation of asbestes bodies does not however gee seem to be - the sole cause of plaque formation does not appear to be consistent with the gh second assumption of Dr. Themison ont Further work is certainly needed to shed light on this important area as the occurrence of ferruginous called asbestos bodies has been found cw ak Dr. D. Murray Angevine March 8 1967 Page 2 tat, in almost half 48 of the individuals studied at autopsy in Montreal by Thuribeck Fortunately plans for such are being made through cooperative efforts involving industry government universities and private institutions as was pointed out in a recent meeting held by Industrial Hygiene Foundation IHF and reported in HF Medical Series Bulletin No. 11 entitled Asbestos Bio- effects Research for Industry A limited mmber of copies of this publication request will be made available to readers of Archives of Pathology upon with- , out charge while the supply lasts Sincerely yours doT sje ce Dr. Paul Gress bec Mr. E. K. Davison Mr. Hugh Jackson Jackson Robert T. P. deTreville M. Managing Director eee Enclosures: All four references were sent the angevine- angevine- 1. Transactions of Industrial Hygiene Foundation 31st Annual Meeting 1966 2. Industrial Hygiene Foundation Medical Series Bulletin No. 11 Asbestos Bioeffects Research for Industry 1966 3. The Pneumoconioses New York 1963 A.J. Lansa Editor Grune & Stratton Inc. 4. The Incidence of Asbestos Bodies in the Lungs at Random Necropates in Montreal Lily Anjiivel and W. M. Thurlbeck Can Med Assn J. 95 1179-1182 Dec. 3 1966 PRODUCED JM - 83 te. a. - APPENDIX E AMERICAN MEDICAL ASSOCIATION 535 NORTH DEARBORN STREET . CHICAGO , ILLINOIS 60610 PHONE 312 527-1500 TWX 910-221.0300 MURRAY 0. ANGEVINE MD Chief Editor DepartmenUniverstity of PathologyWisconsin School of Medicine 470 North Charter Street Madison Wisconsin 53706 JOHN H. TALBOTT MD Director Division of Scientific Publications ROBERT W. MAYO Executive Managing Editor NORMAN D. RICHEY Managing Editor Editor : ARCHIVES BOARD PATHOLOGY PATHOLOGY M. ARCHIARACHRICHI H. BAGGENSTOSS MD RochesteMirnn KENNETH M. BRINKHOUS MO Chapel Hill N.C. JOSEPH FELCMAN MD La Jolla Calif SAMUEL P. HICKS MD Ann Arbor Mich PAUL KOTIN MD Bethesda Md PAUL E. LACY MD St. LouIS HENRY HENRY D. MOON MO San Francisco JOHN L. SHAPIRO MO Nashvilla Tann C. BRUCE TAYLOR MO Evanston III April April 4 , 1967 Robert T. P. deTreville M.D. Managing Director Industrial Hygiene Foundation of America Mellon Institute 4400 Fifth Avenue Pittsburgh Pennsylvania 15213 Inc. nm - Dear Dr. deTreville ~ I wish enclosures to thank you for your letter of March 8 together with After careful consideration I do not believe it advisable to publish further correspondence on this matter in the Archives of Pathology It would seem that after the initial exchange of opinions in print that further discussion should be by correspondence of participating parties I debate reader assure you but rather interest that than this is not a deliberate a continuation of it may . attempt to curtail not be of large DMA cg Sincerely yours oMurray D. Murray Angevine Chief Editor Archives of Pathology _ PRODUCED JM - 83 MANVILLE RESEARCH & ENGINEERING CENTER P.O. BOX 159 MANVILLE NEW JERSEY TELEPHONE 201 RANDOLPH 2-9000 tat. J Jf wv April 12 1967 | Dr. Paul Gross Director of Research Laboratory Industrial Hygiene Foundation of Mellon Institute 4400 Fifth Avenue America Pittsburgh Pennsylvania 15213 Inc. Dear Dr. Gross oe . oe aes ' I am sending under separate cover two samples of synthetic chrysotile for use in your research These samples were prepared by Dr. Julie Yang of our laboratory The sample labeled Synthetic Chrysotile is the purest material ) we have been able to synthesize The impurities which are present see attached ee used table of properties were probably contaminants in the magnesium hydroxide c as a raw material It is unfortunate that we were not able to grow longer oye ees | fibrils but this requires the use of a mineralizer which would introduce un- wanted impurities into the system aia Tidiee * The sample labeled containing Synthetic Chrysotile contains 2.2 per cent nickel The nickel is most probably in the divalent form and substituted for micrographs the magnesium in the chrysotile lattice Electron are attached ot of both sample*s:: . Very truly yours mac Attachment Jama a Me! : P. Leineweber Chief het . Basic Chemistry Research Section  - . a es ATTACHMENT a - * 7 a Synthetic Chrysotile ray Diffraction Electron Micrographs A. Morphology B. Size Ignition Loss @ 1800F Impurities by Emission Spectrograph Chrysotile . Fibrous Up to 5 microns 13.2 Al Ca Fe Cr 0.018 0.18 0.017 -- Cu -- -. Synthetic Chrysotile Chrysotile Fibrous Up to 2 microns 12.7 -- 0.02 0.14 0.06 0.06 | 0.10 2.2 . a " . j : . s _ ; ao PO, - oo oe Concentrations reported as element not oxides Wo nee aed ieeee-+a Bagsaat7 . ireneat ee a re 7 Jackson Sree Ri TV T a eee ee oot g ape ve HHygyienegieneeit, Fibrous subject agyoou asked Resreeavricewh Industrial me 'the : Bee ye Dusts = : a aproposal on this submi 3 Foundation to five companies After discussions with the Foundationstaff the was revised to include additional dusts proposal -* thus broadening the scope of the researchAnother sponsor was included * RecentlyI'net withDr. Gralleyof the U.S.P.H.S. Dr. Vorwald from Detroit and Dr. Clefv roe m Cl lea ven landd to ascertain if they were undertaking any studies which would duplicate the proposed research there wilHlappily duplidationImmable 0 = research progres *and z:stronglyrecommendthat ; oF y Bro and be a sponsor in this researchagreement areattached Corning Pittsburgh * in ittsburghi already _ ments with the Foundation Mr. Edwards of have Fiberglas has stated . woe that his company is willing to be a sponsor Dr. Wolfale has indicated $ similar intent on the part of U. S. Rubber Certain wwiillll follow details companies sg approvalcanobtained able details with the I.H.F. staff and repr^'sentativesof some ofthe other BY companies whileattendinganother meetinginPittsburghnext other r To obtain factual e . chrysotile amosite crocide fibrous glass asbestos fibers . as well as trace elements on the surface: for the fourth year , additional companies agree to become sponsors a 1 t AMERICA INDUSTRIAL HYGIENE FOUNDATION OF _ 7 MELLON INSTITUTE 4400 FIFTH AVENUE . e Pittsburgh 15213 AGREEMENT FOR SPONSORED RESEARCH ee THIS AGREEMENT made and entered into this fifteenth day of April 1966 by and between MANVILLE CORPORATION hereinafter referred to as SPONSOR and INDUSTRIAL HYGIENE FOUNDATION OF AMERICA INC a nonprofit corporation hereinafter referred to as RESEARCHER WITNESSETH RECITAL OF FACTS SPONSOR desires the services of the RESEARCHER in the conduct of study research development and other work related to and for the pur- pose of gaining useful knowledge in the following matter _ dusts An investigation of the factors involveidn the pathogenicity ? dusts of asbestos dust theirtheir applicability | to filamentous glass dust and the specificity of the called asbestos ferritin bodies hereinafter referred to as the PROJECT RESEARCHER desires to under- take this PROJECT for the SPONSOR both parties agreeing to the terms and conditions hereinafter set forth PROD-U8CE3D AN ASSOCIATION OF INDUSTRIES FOR THE ADVANGEMENT OF HEALTHFUL HEALTHFHEUALTLHFUL WORKing conditioNS  INDUSTRIAL HYGIENE FOUNDATION OF AMERICA INC NOW THEREFORE in consideration of the premises and of the mutual promises and covenants herein contained the parties hereto agree as follows 1. Undertaking SPONSOR engages RESEARCHER to carry out the PROJECT by conducting study research development and other work therein and thereupon and the RESEARCHER agrees to undertake and carry out the PROJECT using its best efforts in performing such work and devoting to it such time and attention as is reasonably required for the sufficient progress of the PROJECT The PROJECT will be under the direct supervision of the RESEARCHER'S Research Pathologist 2. Effective Date Term and Termination This agreement shall become effective on June , 1966 and shall terminate on May 31 1969 . 3. Progress Progress Reports RESEARCHER agrees to make progress reports periodically as indicated setting forth the findings and progress made in the course of the PROJECT and other information pertinent thereto The final report will be submitted May 31 1969 PRODUCED * INDUSTRIAL HYGIENE FOUNDATION OF AMERICA 4. Publication Rights It is also agreed that no advertising promotional or publicity matter containing any reference to the RESEARCHER or to any of its employees shall be made use of by the SPONSOR or anyone in the SPONSOR'S behalf unless and until the same shall have first been submitted to and received the approval in writing of the RESEARCHER The RESEARCHER reserves ex- clusive right to publication of material developed in the Industrial Hygiene Foundation of America Inc. journals if the results of the timingtiming Research Laboratory in suitable scientific research merit publication however the RESEARCHER will not publish any findings in association with the name of the SPONSOR unless the SPONSOR gives permission es 5. Charges . RESEARCHER'S charge for partial support of the Industrial Hygiene Foundation of America Inc. Laboratory Research in carrying out the PROJECT and partially covering compensation to personnel engaged in carrying on the a work clerical and consultative services and preparation and printing of a report will be Ten Thousand Dollars 10,000 from Inig 1 1966 to May 31 1967 Ten Thousand Dollars 10,000 from June 1 1967 to May 31 1968 and Ten . Thousand Dollars 10,000 from June 1 1968 to May 31 1969 6. Independent Contractor It is agreed and understood that the RESEARCHER is acting as an independent contractor in the performance of any and all work hereunder 3 po PRODUCED PRODUCED INDUSTRIAL HYGIENE FOUNDATION OF AMERICA and that the SPONSOR shall not be liable and responsible for the payment of any and all legal claims for damages made by the RESEARCHER'S employees or agents or by any other person or persons on account of any property damage or personal injury sustained or suffered by or the death of any person or persons arising or growing out of or in connection with the performance of this agreement or any act or omission in connection herewith and RESEARCHER hereby indemnifies and agrees to hold SPONSOR harmless against any and all such claims ' IN WITNESS WHEREOF the parties hereto have executed this agreement on the day and year first above written JOHNS MANVILLE CORPORATION BY SPONSOR INDUSTRIAL HYGIENE FOUNDATION OF AMERICA INC Robert TreviTlrleville Managing Director RESEARCHER ma PRODUCED INDUSTRIAL INDUSTRIAL ee HYGIENE FOUNDATION OF AMERICA MELLON INSTITUTE 4400 FIFTH AVENUE Pittsburgh Pa 15213 June 1 1966 Prospectus for An Investigation of a The Specificity of Asbestos Bodies and b The Biologic Effects of Trace Substances Associated with Chrysotile Asbestos INTRODUCTION ) 1 Thomson found that about 30 of the people that had died in hospitals in Capetown 500 consecutive autopsies had asbestos bodies in the lungs The same author found a similar prevalence of asbestos bodies among hospital the deaths in Miami Florida Cauna Totten and Gross examined the lungs of 100 selected hospital deaths for which autopsy permission had been obtained and found that 40 of these had asbestos bodies in their lungs Ian Webster recently reported a 47 prevalence in Johannesburg There is at present a reasonable doubt that asbestos bodies are specific indicators of the inhalation of asbestos fibers Such bodies have been found in coal miners and talc workers where they have been called asbestos bodies Recently Davis and Collet 6 have demonstrated the intracellular development of asbestos bodies secondary to amorphous material AN ASSOCIATION OF INDUSTRIES FOR THE ADVANCEMENT OF HEALTHFUL WORKING CONDITIONS PRODUCED Nar INDUSTRIAL HYGIENE FOUNDATION OF AMERICA 2 Asbestos occupies an anomalous position in its ability to produce lung damage causing diffuse fibrosis and possibly also lung cancer It is anomalous inasmuch as no other silicate has been shown to possess this ability The fibrosis encountered in talcosis is limited to the tremolite variety which is asbestos On the other hand the pneumoconiosis associated with _ the mining of mica another silicate has not been investigated experimentally and the fibrogenic activity of the dusts coexisting with the mica 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 trace metals known to be potent producing agents have been demonstrated in asbestos particularly nickel chromium and benzopyrene the possibility exists that the trace metals and the polycyclic hydrocarbons may be solely responsible for the observed pathogenicity This possibility is supported by two findings 1. The report of Braun and Truan which indicated that the preva- lence of lung cancer among Canadian asbestos miners was no greater than that of the general population This was in contrast to the report of Doll which indicated a greatly increased risk of lung cancer among British workers exposed to asbestos dust while fabricating the asbestos 2. In recent investigation in the laboratory of the Industrial Hygiene Foundation lung cancers were found in rats exposed for 18 months to high concentrations of chrysotile dust 9 Because rats exposed to chrysotile by other investigators failed to develop lung cancer there is a good probability PRODUCED oA -83 -83 FOUNDATION w INDUSTRIAL HYGIENE FOUNDATION OF AMERICA.INC 3 that the chrysotile dust that produced lung cancer was significantly different from that which did not have this effect It is possible that this difference is caused by a coating of nickel steel alloy applied to the asbestos dust particles during the continuous hammer milling process used for rendering the dust respirable This method has not been used by previous investigators Nickel has been found capable of producing lung cancer in trace amounts Although asbestos and glass are both silicates the industrial health experience with workers of these two materials has been vastly different No pulmonary disease has been reported in workers exposed to glass dust Nevertheless the dust of filamentous glass has been labeled as highly dangerous in the lay press by association with asbestos It is a fact that although the effect of flake glass dust on the lungs of animals has been reported no similar study has been made of the dust of filamentous glass which does not have an associated resin or filler PROPOSAL Phase 1 It is proposed to examine the response of animals lungs to different inorganic fibrous materials of contrasting chemical composition and to characterize the differences and similarities in the response Phase 2 It is proposed to investigate the influence of trace minerals and polycyclic hydrocarbons e benzopyrene associated with chrysotile ore or the subsequent processing on the term response of the lung to the dust PRODUCED JM - 83 \eteor vi INDUSTRIAL HYGIENE FOUNDATION OF AMERICA.INC 4 Another objective of this phase is to obtain definitive data on the long- term effect of dust derived from filamentous glass upon the lungs Three varieties of such glass dust will be investigated 1 with the formaldehyde of binder 2 with the binders used in textiles 3 without binder Phase 3 A comparative study of the three main types of asbestos dust chrysotile amosite and crocidolite is proposed to attempt to pinpoint the cause of biological activity i e whether due to silicates per se or the associated trace metals or hydrocarbons Positive findings would be a basis for identifying any possible health hazards and for suggesting specific engineering or other process controls to eliminate such hazards MATERIALS AND METHOD Phase 1 The following fibrous materials will be reduced to respirable particle size 3... and will be injected in amounts of 3.5 mg | to 30 mg as aqueous suspensions 1 chrysotile dust prepared by milling in Wright mill and with demonstrated carcinogenic potential 2 chrysotile dust unmilled synthetic 3 aluminum nitride 3 tricalcium phosphate filamentous 5. fibrous glass a with formaldehyde binder = with binder used for textiles C. without binder 6 magnesium hydroxide brucite 7 mineral wool 8 zinc oxide filamentous PRODUCED PRODUCED * Synthetic chrysotile has been prepared at Mellon Institute by Dr. William Granquist Electron photomicrographs show the characteristic J-M 83 FOUNDATION . INDUSTRIAL HYGIENE FOUNDATION OF AMERICA.INC 5 These materials will be injected intratracheally into hamsters under ether anesthesia Previous experience has demonstrated that asbestos bodies will form in response to chrysotile dust within five months The animals will therefore be held for six months and then killed Asbestos bodies will be sought in lung juice as well as in the lung tissues The lungs will be expanded with buffered formalin under a head of 10 cm of water Blocks removed from these lungs will be sectioned at after paraffin impregnation These sections will be stained by different methods and photographed sequentially to provide means for studying more completely the tissue reaction to these various materials Search for the called asbestos bodies will be made using routinely stained sections and | sections stained for iron In addition unstained cleared sections will be examined under field conditions for asbestos bodies The latter glow when examined in this manner The difference in tissue reaction between the synthetic chrysotile dust and that which is known to be fibrogenic as well as carcinogenic will point to the contribution to pathogenicity made by one or more of the various trace substances which may be associated with chrysotile asbestos dust as a result of processing The development of asbestos bodies better termed Ferruginous bodies to dusts other than asbestos would point to the specificty of these structures and to the desirability of collecting such asbestos bodies from human lungs in order to subject them to electron analysis Such PRODUCED JM - 83 ao 6 6 INDUSTRIAL HYGIENE FOUNDATION OF AMERICA INC to the chemical make of the dust analysis could give information in regard for the development of the Ferruginous asbestos body responsible Phase 2 role of the various components of In order to explore the etiologic chrysotile asbestos in the production of lung fibrosis and lung cancer six series of rats will be injected intratracheally with the following carcinogenic 1. 1. chrysotile dust known to be : 2. synthetic chrysotile synthetic chrysotile plus nickel chrysotile synthetic plus chrome synthetic chrysotile plus nickel chrome nickel alone or with carbon as carrier and benzopyrene chrome alone or with carbon as carrier 7. 4. with carbon as carrier benzopyrene for killed These rats will be held two years and then The lungs will and sections cut in the same manner as in be prepared for examination | Phase . Three other series of rats will be injected intratracheally with the following dusts formaldehyde binder 1. filamentous glass with with the binders used for textiles 2. filamentous glass 3. filamentous glass without binder These animals will also be held for two years and then killed The lungs in the preceding groups with special attention will be prepared and studied as to asbestos bodies in lung tissues or juice series will be such that there will be The number of animals per of the results no doubt regarding the statistical significance PRODUCED JM - 83 FOUNDATION wee INDUSTRIAL HYGIENE FOUNDATION OF AMERICA INC 7 Phase 3 SUPPLEMENTARY PROPOSAL Note The following supplement has been added to the original proposal of April 15 1966. INTRODUCTION Because of the interest of a number of companies in biologic investigations similar to those planned for chrysotile asbestos but using instead amosite and crocidolite an additional investigation is proposed to be undertaken concurrently with the one proposed April 15 1966 As in the proposal dealing with chrysotile asbestos the purpose pinpoint of the presently proposed concurrent investigation is to attempt to | the cause of the biologic activity of all three main types of asbestos dusts whether this lies in the silicates per se in the associated trace metals or in the associated hydrocarbons Because neither amosite nor crocidolite is available as a pure synthetic material the investigation proposed for these two types of asbestos is necessarily different from that proposed for chrysotile Never- theless in order to make the investigation complete it is desirable to include also chrysotile in the new investigation since different methods are involved Inasmuch as the biologic activity of asbestos seems to have two components a inflammatory for asbestosis and b neoresponsible for lung cancer and mesothelioma it is advisable to PRODUCED JM - 83 ad INDUSTRIAL HYGIENE FOUNDATION OF AMERICA ? 8 investigate both of them This can readily be accomplished within the four year span contemplated for this investigation In order to determine whether the biologic activity of asbestos resides in the silicate in the associated trace metals or in the associated hydrocarbons attempts will be made to remove the trace metals and the hydrocarbons from their respective silicates and to compare the biologic activities of such purified asbestos samples from which these associated materials have been removed PROPOSAL As a prerequisite to any biologic testing insofar as the lungs are concerned it is necessary to reduce the asbestos to a respirable particle size This will be done in the following manner the amosite and crocido- lite will be milled and then fed into continuous hammer mills modified from a design by Holt and Young 10 The dusts emerging from the hammer mills will be collected in electrostatic precipitators This method has been used successfully by us to reduce chrysotile asbestos to a particle size 70 of which was respirable A sufficient quantity of finely divided chryso- tile dust is available for the purposes of this investigation All three types of asbestos dust will be deprived of the greater portion or of all of their hydrocarbon content in one of two ways 1 by continuous extraction with various solvents 2 by heating beyond the decomposition point of the hydrocarbons The trace metals will be removed from the three types of asbestos dust by treatment with aqua regia followed by treatment with EDTA ethylene diamine tetraacetic acid a chelating agent PRODUCED JM - 83 aw ww 9 AMERICA INDUSTRIAL HYGIENE FOUNDATION OF One batch of each type of asbestos dust will be subjected to both procedures i.e. removal of trace metals and removal of hydrocarbons of asbestos dust will consist of Accordingly each of the three types five batches each with a different composition treated 1 the unaltered dust as collected in the precipitators Here 2 the dust minus the hydrocarbons that there may also have been some change it is anticipated loss of in the chemical structure of the asbestos through some molecules of water of hydration dust minus the hydrocarbons solvent extraction Here 3 the not be 100 complete it is anticipated that the extraction may 4 the dust minus trace metals then subjected to solvent extraction 5 the dust minus trace metals to remove most of the hydrocarbons the inflammatory component of the various In order to investigate 15 batches of asbestos dust these will be injected rats and hamsters The lungs of these animals are intratracheally into expected to show definitive one changes within introduction of the dusts year after the intrapulmonary In order to explore the lung cancer aspect of the neoplastic com- biologic ponent of the of asbestos dust additional rats will be injected activity and allowed to live out their lives with the same batches of dust as above Most of the animals however will have died before the end of the third year of the above neoplastic com- The other mesotheliomatous aspect ponent will dust within be investigated by the pleural cavity injecting the 15 different of rats and hamsters and batches of asbestos allowing them to live out their lives will also have died before the end of Most of these animals the third year PRODUCED JM - 83 wd INDUSTRIAL HYGIENE FOUNDATION OF AMERICA.INC 10 For the investigation of the inflammatory component of asbestos dust a large enough number of animals will be put on test to allow sampling at intervals throughout the year and still have an adequate number remaining to represent the 12 month old lesion A tabular summary of the protocol is attached REPORTS Definite trends in regard to the inflammatory component are expected to be demonstrable in animals that will be killed prior to the 12 month period as indicated under footnote b in the Tabular Summary An interim report covering the findings in these 420 animals will therefore be issued at the end of the first year Because few if any tumors are expected to develop prior to 24 months no interim report on the neoplastic component will be issued until the end of the third year The final report covering the entire investigation will be issued toward the end of the fourth year This report will probably be in the form of several manuscripts suitable for publication SUPERVISION Research will be performed under the direct supervision of Dr. Paul Gross Director of the Foundation's Research Laboratory The Foundation's studies on asbestos presently are being conducted under partial support of the U. S. Government through a National Institutes of Health grant and a contract with the U. S. Public Health Service Division of Occupational Health Dr. Lewis J. Cralley PRODUCED JM - 83 FOUNDATION ~w INDUSTRIAL HYGIENE FOUNDATION OF AMERICA.INC 11 TABULAR SUMMARY OF PROTOCOL Asbestos of Asbestos Asbestos Asbestos Type Asbestos a Dust Injected Intratracheally Batch for Batch | Inflammatory Component for Lung Cancer No. No. Rats b ) No. No. Hamsters No. No. Rats Chrysotile I 20 20 20 Chrysotile 2 20 20 20 Chrysotile 3 20 20 20 Chrysotile 4 20 20 20 Chrysotile 5 20 20 20 Dust Injected Intrapleurally for Mesothelioma No. No. Rats No. No. Hamsters 20 20 20 20 20 20 20 20 20 20 WNE 20 20 Amosite WNE 20 20 Amosite WNE 20 20 Amosite 4 20 20 Amosite 20 20 20 20 20 20 20 20 20 20 20 20 20 20 20 20 20 Crocidolite 123 Crocidolite 123 Crocidolite 123 Crocidolite 4 Crocidolite 5 TOTALS 20 20 20 20 20 300 20 20 20 20 20 300 20 20 20 20 20 300 20 20 20 20 20 300 20 20 20 20 20 300 a The following batches are identified No. 1 = dust as collected from electrostatic precipitators No. 2 = dust extracted with solvents No. No. No. 3 = dust heated to decompose hydrocarbons 4 = dust treated with aqua regia and EDTA 5 = dust treated as with No. 4 and No. 2 b Two animals killed immediately after the dust injection Four animals killed 4 days after the dust injection Four animals killed 1 month after the dust injection Four animals killed 6 months after the dust injection Six animals killed 12 months after the dust injection c All animals allowed to live out there lives PRODUCED JM - 83 INDUSTRIAL HYGIENE FOUNDATION OF AMERICA INC 12 REFERENCES 1 Thomson J.G. al Asbestos as Modern Urban Hazard S. Afr Med J. 77-81 1963 2 Thomson J.G. , al Asbestos as an Urban Air Contaminant Arch Pathol 458-464 May 1966 3 Cauna Dzidra Totten Robert .; and Gross Paul Asbestos Bodies in Human Lungs at Autopsy JAMA 371-373 May 3 1965 4 Webster Ian Report of progress quoted in the Annual Report of the Pneumoconiosis Research Unit of the South African Council for Scientific and Industrial Research 1965 5 Davis M.G. Microscope Studies of Asbestosis in Man and Animals Ann Y. Acad Scie 98-111 1965 6 Collet A. Personal Communication 1965 17 7 Braun Daniel C. and Truan T. David An Epidemiological Study of ~ Lung Cancer in Asbestos Miners AMA Arch Ind Health 634-653 June 1958 8 9 10 Doll R. Mortality from Lung Cancer in Asbestos Workers Ind Health 12:81 1955 Brit J. Gross P. and Treville R.T.P. Experimental Asbestosis Studies on the Progressiveness of the Pulmonary Fibrosis Caused by Chrysotile Dust To be published Holt P.S. and Young D. K. A Feed Mechanism Suitable for Fibrous Dust Ann Occ Hyg 245 1960 PRODUCED JM - 83 4 te INDUSTRIAL HYGIENE FOUNDATION OF AMERICA MELLON INSTITUTE 4400 Fifth Avenuj 6 REC'D IHF IHF Fibrous Fibrous DUST DUST ST , PITTSBURGH PA 15213 June 3 1966 Mea enere TO Mr. Leon Horowitz Mr. C. L. Sheckler Mr. F. H. Edwards Dr. Lee B. Grant _ Dr. J. H. Wolfsie Certain Products Corporation ' Manville Corporation = Corning Fiberglas Corporation ue Pittsburgh Plate Glass Company < U. S. Rubber Company . Regarding my letter of April 14 during the past month it has become ap=. ' parent that the Foundation's original proposal for an investigation of the specificity wee chryso- of asbestos bodies and the biologic effects of trace substances associated with |jy tile asbestos was not sufficiently comprehensive in that it did not cover the amosite : a-a and crocidolite forms of asbestos which are of interest to industry It will be recalled _ that the original study depended on the availability of synthetic chrysotile through - Mellon Institute inasmuch as synthetic amosite and crocidolite are not available saredcaeled ' , #2 Dr. Gross suggests that a separate additional study attached be performed con, currently The supplemental study requires more animals and will be extended an - additional year It is thus estimated that the original budgetary requirements will| ; be 100,000 during the first three years and 50,000 in the fourth for a total of x 350,000 Each sponsor listed above would thus pay 20,000 during the year eo oy July 1 1966 to June 30 1967. The Foundation is prepared to undertake these studies if sponsors listed will sign both copies of the Revised Agreement for Sponsored - Research returning one copy and retaining the other for sponsor's files a oy It now appears that support for the second third and fourth years may : very well develop on a broader base Dr. Gross has been invited to present our proposal before the Asbestos Textile Institute on June 9 and a similar briefing will be scheduled for the National Insulation Manufacturers Association and also any k:)other large asbestos manufacturing companies not covered under these industrial a associations J 7 Are ay |:; ; 2 % Sie - ; 3. . : informal during impression From discudions iscussions the past month it is our ! that each company receiving this letter wishes to keep on schedule and have the = Foundation initiate work on July 1. A prompt response indicating approval would ae provide Dr. Gross with a stronger proposal to present to the Asbestos Textile Ivnesrtiytute support on June 9 in hopes of extending the base of a-dvantageous from many respects this would of course be Please call Dr. Gross or meif further questions arise . . Enclosures AN ASSOCIATION OF INDUSTRIES FOR Bobut M.D. detreville THE ADVANCEMENT ManagingManaging DiDirreectcortor WORKING CONDITIONS PRODUCE PRODUCE JM He ow ot a a ary : . een me ee Or oe ee ee ee ce! pecki INDUSTRIAL HYGIENE FOUNDATION OF AMERICA 7 en were STUDY FIBROUS MATERIALS how fe. . is OF received + = of the IHF proposed appears that proposal AC revised copy study and contract this ;includesmositeandcrecidolite forms ail Origin The financial aspects mr is somewhat pay ofthe study confusiconrgporation v OS" @ were five corporations involved with the request that each three 10,000 between the present date ep year for a three year period and the USPHS would supplement that sun overa4. three :q.;, year period The cost April 14th letter and by increased to 20,000 a year per corporation for three years plus ' fox would | a would 10,000 additional year or as I interpret the contract the total per corporation 70,000 forthree instead 30,000 for period be years of additional the same ) i, ae proposal Rubber I doubt very much that Pittsburgh Plate Glass will agree to an this Products U. 8. and expenditure of size consideri consideri consideri is corporations that their interest in amosite and crocidolite crocidolite is minimal Unless a joint industry study with at least the five original participating ; particpating it could very well result in being labelled biased and we would find ourselv the sameposition at thefi Ethyl Corporation mdtheir leadstudies ; INDUSTRIAL HYGIENE FOUNDATION OF AMERICA INC IHF MELLON INSTITUTE 4400 FIFTH AVENUE Study Fitions Fitions Dust Dust Study PITTSBURGH PA 15213 REVISED AGREEMENT FOR SPONSORED RESEARCH k a THIS AGREEMENT made and entered into this first day of June _ 1966 by and between MANVILLE CORPORATION _ hereinafter referred to as SPONSOR and INDUSTRIAL HYGIENE FOUN- a DATION OF AMERICA INC , a nonprofit corporation hereinafter referred to as RESEARCHER WITNESSETH a: : 7 oy RECITAL OF FACTS SPONSOR desires the services of the RESEARCHER in the conduct of study research development and other work related to and for the pur- a : pose of gaining useful knowledge in the following matter An investigation of the factors involved in the pathogenicity _ of asbestos dusts and of filamentous glass dusts and the specificity of the called asbestos ferruginous bodies hereinafter referredto as the PROJECT RESEARCHER desires to under- : take this PROJECT for the SPONSOR both parties agreeing to the termsci and conditions hereinafter set forth _ * Supersedes Agreement for Sponsored Research dated April 15 1966' \ . _ INDUSTRIAL HYGIENE FOUNDATION OF AMERICA INC NOW THEREFORE in consideration of the premises and of the mutual promises and covenants herein contained the parties hereto agree as follows bwft 4 . 1. Undertaking SPONSOR engages RESEARCHER to carry out the PROJECT by conducting study research development and other work therein and thereupon and the RESEARCHER agrees to undertake and carry out the . PROJECT using its best efforts in performing such work and devoting to it such time and attention as is reasonably required for the sufficient progress of the PROJECT The PROJECT will be under the direct supervision of thej RESEARCHER'S Research Pathologist 2. Effective Date Term and Termination This agreement shall become effective on July 1 1966 and shall terminate on June 30 1967. At the termination of each contract year agreements for continued support for subsequent years will be submitted 3. Progress Reports ' So te RESEARCHER agrees to make progress reports periodically as _ indicated setting forth the findings and progress made in the course of the _ PROJECT and other information pertinent thereto submitted June 30 1970 The final report will be PRODUCED a. ee ' INDUSTRIAL HYGIENE FOUNDATION OF AMERICA.INC 4. Publication Rights ore | It is also agreed that no advertising promotional or publicity matter containing any reference to the RESEARCHER or to any of its employees shall be made use of by the SPONSOR or anyone in the SPONSOR'S behalf a unless and until the same shall have first been submitted to and received the 4 approval in writing of the RESEARCHER The RESEARCHER reserves ex- ; % clusive right to publication of material developed in the Industrial Hygiene Foundation of America Inc. Research Laboratory in suitable scientific journals if the results of the research merit publication however the RESEARCHER will not publish any findings in association with the name of cad ie ; wy the SPONSOR unless the SPONSOR gives permission 5. Charges RESEARCHER'S charge for partial support of the Industrial Hygiene Foundation of America Inc. Laboratory Research in carrying out the PROJECT and partially covering compensation to personnel engaged in carrying on the work clerical and consultative services will be Twenty Thousand Dollars . 20,000 for the period extending from July 1 1966 to June 30 1967 i Continued support for the period extending from July 1 1967 to June 30 1970 will be a maximum of 20,000 per SPONSOR per year for the second and | third years and 10,000 for the fourth year It is hoped that additional SPONSORS will support the project in the second third and fourth years : thereby reducing the total cost per SPONSOR in subsequent years 3 | PRODUCED JM - 83 * * ipa 2 INDUSTRIAL HYGIENE FOUNDATION OF AMERICA 6. Independent Contractor : It is agreed and understood that the RESEARCHER is acting as an independent contractor in the performance of any and all work hereunder and that the SPONSOR shall not be liable and responsible for the payment of any and all legal claims for damages made by the RESEARCHER'S em- a ou . er ployees or agents or by any other person or persons on account of any property damage or personal injury sustained or suffered by or the death of any person or persons arising or growing out of or in connection with the performance of this agreement or any act or omission in connection herewith and RESEARCHER hereby indemnifies and agrees to hold SPONSOR harmless against any and all such claims ,, IN WITNESS WHEREOF the parties hereto have executed this agreement on the day and year first above written . & . MANVILLE CORPORATION n INDUSTRIAL HYGIENE FOUNDATION OF AMERICA INC Managing Director RESEARCHER PRODUCED 412 687-2100 ESTABLISHED 1935 . INDUSTRIAL HYGIENE 5231 CENTRE AVENUE FOUNDATION OF AMERICA INC ss mf \ PITTSBURGH PA 15232 December 23 1968 TO THE SPONSORS OF IHF FIBROUS DUST STUDY 9 F 12/4 is Mr. Mr. Dr. Hugh M. Jackson Russell Brittingham Lee B. Grant Dr. Jon L. Konzen Dr. Joseph L. Goodman Manville Corporation Pittsburgh Corning Corporation PPG Industries Corning Fiberglas Corporation Raybestos Manhattan Inc. i eo be a In the past our reports of progress usually have been submitted to sponsors on dates specified in our research agreements our first We are now considering instituting quarterly reports and oo such attempt is enclosed herewith To supplement the written text we have developed a new systeomf tabulation which we hope will aid its comprehensibility Your comments in your behalf pro or con ; ~ are solicited to guide our future efforts ; Best wishes for the holiday season and New Year Sincerely Kukut eee P deT Enclosure cc Mr. C. L. Sheckler on Robert T. P. deTreville M.D. ' President