Document RZG5pQDaEMa3NDXYw8208dBV

FILE NAME Manville JMA DATE 1967 Feb 14 DOC JMA210 DOCUMENT DESCRIPTION Report - Preliminary Study of BrakeDrum Dust Comparative Pathogenicity INDUSTRIAL HYGIENE FOUNDATION OF AMERICA MELLON INSTITUTE 4400 Fifth Avenue PITTSBURGH Pa 15213 Report on PRELIMINARY STUDY OF BRAKE DUST COMPARATIVE PATHOGENICITY for MANVILLE CORPORATION by Paul Gross M.D. Director of Research Laboratory . February 14 1967 Robert T. P. deTreville M.D. Managing Director AN ASSOCIATION OF INDUSTRIES FOR THE ADVANCEMENT OF HEALTHFUL WORKING CONDITIONS INDUSTRIAL HYGIENE FOUNDATION OF AMERICA INC 1 Introduction As an explanation for the occurrence of ferruginous asbestos bodies in the lungs of 30 to 40 of the general population in large cities Thomson has indicated that urban populations are being exposed to asbestos dust and that a likely source of this dust was from the wearing down of automobile brakes Details of Preliminary Study At the request of Dr. Kenneth W. Smith Medical Director Johns ville Corporation a preliminary study of the pathogenicity of brake dust was done This dust free of iron was suspended in water and 1 ml containing 3.5 mg was injected intratracheally into rats and hamsters Some of the rats were killed four days later The lungs were examined microscopically and the changes compared with the four lesions seen in the lungs of rats injected intratracheally with the dusts of a crystalline silica b chrysotile and c kaolin respectively The chrysotile had been similarly suspended in water and given in the same dosage Results The results were as follows crystalline silica and chrysotile caused a severe inflammation best described as an obliterative bronchiolitis that could not be differentiated one from the other Whereas reactions caused by both kaolin and brake dust were also similar to one another and were of the called biologically inert type This reaction consisted essentially of the accumulation within scattered alveoli of scavenger cells filled with the respective INDUSTRIAL HYGIENE FOUNDATION OF AMERICA.INC . 2 dusts There was no significant development of the connective tissue that in the case of silica and chrysotile tended to obliterate the air spaces and ducts Tentatively therefore the brake dust tested should be categorized as biologically inert Recommendations for Further Studies A proposal for further investigation of the pathogenicity of brake dust has been prepared at the request of Manville Corporation Analytical laboratories at Manville Corporation have reportedly been unsuccessful in identifying asbestos fibers in brake dust and the Industrial Hygiene Foundation's preliminary studies have shown that the dust behaves differently than chrysotile asbestos with effects on lungs which closely resemble those produced by inert dusts such as kaolin If these findings should be borne out by further studies their publication would help prove that Thomson's assumption was erroneous Essential to publication would be the development of data from inhalation of brake dust by adequate numbers of several species of laboratory animals Tentatively it is suggested that of 40 animals in each of four species guinea pigs rats hamsters and mice 30 be exposed over most of their life span two years in all except mice which have a shorter life span and require only one year to a concentration of about 100 mg the other 10 serving as controls This con- centration would be produced in an 8 x 8 x 8 chamber by means of Wright dustfeed dispersion equipment Frequent quantitation of the chamber atmosphere close INDUSTRIAL HYGIENE FOUNDATION OF AMERICA.INC 3 observation and care of the animals and extensive histopathological observations would be necessary over a three period of research The cost would be 200,000 200,000 50,000 the first two years and 100,000 the third Histological sections will receive special staining and microscopic examination by research pathologists who will take thousands of photomicrographs of their findings and use some of these to document their report which will be suitable for publication As a means of developing additional information which cannot take the place of the inhalation study but will give earlier indication of lung changes it is recommended that a similar study be done by intratracheal injection technique giving 80 animals 20 of each species listed above a single injection of near maxi- mal dose tolerated without death These animals would be pastured for one year killed and examined by the same research pathological techniques The year study would cost 75,000 25,000 25,000 the first year and 50,000 50,000 the second the second year including the histopathological studies and preparation of a report Although not considered adequate for publication alone the results by injection would be incorporated with the inhalation study findings and be a valuable supple- ment to it Costs of the combined studies will be 275,000 75,000 75,000 the first year and 100,000 100,000 on each of the two successive years References 1 Thomson J.G. et al Asbestos as Modern Urban Hazard S. Afr Med J. 77-81 1963 . 7 $ INDUSTRIAL HYGIENE FOUNDATION OF AMERICA.INC Tentative Outline of Brake Dust Investigation A. Intratracheal Injection 75,000 20 Guinea Pigs 20 Rats 20 Hamsters 20 Mice Single injection of maximal dose tolerated without death Pastured for one year and killed B. Inhalation 200,000 200,000 a 40 Guinea Pigs b 40 Rats C. 40 Hamsters d 40 Mice 8 x 8 x 8 chamber Wright feed dispersion at least two needed year exposure Concentration100 Concentration100 Concentration100 mg year exposure for mice because of shorter life expectancy year exposure for others month holding period Six months for processing and writing report Total Three Study Cost 275,000 00310410639 0310410639 0310410639 0 310410639 0 310410639 0310410639 00310410639 COPY INDUSTRIAL HYGIENE FOUNDATION OF AMERICA INC MELLON INSTITUTE 4400 FIFTH AVENUE PITTSBURGH Pa 15213 PRELIMINARY INVESTIGA of the PULMONARY HAZARD CREATED BY BRAKE DUST JOHNS MANVILLE CORPORATION by PAUL GROSS M. Director of Research Laboratory May 1967 11/29/81 11/29/81 B 00370410640 00370410640 00370410640 INDUSTRIAL HYGIENE FOUNDATION OF AMERICA ING Iron brake dust a little less than i gm was obtained from Dr. Kenneth W. Smith Portions of this dust were suspended in water so that 1 ml contained 3.5 mg The investigation is divided into two components a short study and one of longer duration 1. Short Study The purpose of this study was to compare the pulmonary lesions produced by this dust in rats with those produced in rats by other dusts whose pathogenic potential is well known or is documented These dusts included chrysotile quarts aluminum silicate and silicon carbide The different dust lesions were all produced by the same intratracheal dosage and were all of the same age 4 days Groups of four rats each were injected intratracheally with 3.5 mg of the above dusts respectively including the brake dust Results As can be seen in Figs 1 and 2 the pulmonary reaction to brake- drum dust is essentially limited to a few of the alveoli evaginating off respiratory bronchioles and adjoining alveolar ducts This reaction consists of cellular pro- liferation with a concommitant elaboration of supporting argyophilic stroma thereby causing some mural thickening and the obliteration of a few scattered alveoli In contrast to the lesions produced by chrysstile sad quarts 2 dusts the inflammatory tissue did not extend into the lumen of the alveolar ducts or bronchioles nor were more than a few of the evaginating alveoli affected Indeed the pulmonary reaction caused by brake dust at this time more closely resembles that produced by aluminum silicate and silicon carbide both of which have been demonstrated to belong in the fibrogenic category 3,4 3,4 } Beter Defo ESH 171-0-38 ESH 171-0-38 171-0-38 171-0-38 4/29/14/289/18 4/29/18 28 0370410641 03770410641 0374106 0370410641 0370410641 0377041003704610641 403710410641 INDUSTRIAL HYGIENE FOUNDATION OF AMERICA INC 2 II Longer Study The purpose of this study was to determine a if ferruginous bodies were formed in response to the presence of this dust and b if the character of the pulmonary response would continue to be as mild as seems to have been indicated by the four lesion For these purposes both rats and hamsters were employed Twelve hamsters were injected intratracheally on three different occasions with 3.5 mg of brake dust Three of these were killed for sampling 7 1/2 months after the injection Lung washings were obtained from these animals using a modified LaBelle and Brieger technique The sediments from two were smeared on glass slides and the sediment of the third animal was processed for electron microscopy and electron diffraction study The lungs were processed for microscopic study Ten rats were also injected intratracheally with 3.5 mg of brake dust from Manville and held for additional injections and longer survival Results Smears of the sediment from the lung washings of the hamsters showed large numbers of ferruginous bodies many of them segmented and all indistinguishable from asbestos bodies Sections of the lungs of hamsters killed 7 1/2 months after the initial intratracheal injection show minimal involvement of the parenchyma The changes are limited to scattered respiratory bronchioles These show focal cellular thicken- ing of their walls and occlusion of a few of their evaginating alveoli by prolifereted cells macrophages and occasionally also by a foreign giant cell In an occasional involved alveolus black pigment is present There is no evidence of collagen formation and significantly the lumens of the affected respiratory bronchides are widely patent Furthermore it should BAU 171.4 BAU BAU D. D. Et 4/22875 4/22875 00010410642 00010410642 00010410642 0010410642 00010410642 0010410642 INDUSTRIAL HYGIENE FOUNDATION OF AMERICA INC 3 be emphasized that except for a few of the alveoli evaginating off some of the respiratory bronchioles the alveolar tissue appears normal This minimal degree of involvement encountered in hamsters injected _ intratracheally with brake dust stands in striking contrast to the diffuse severs and fatal pneumonitis caused by chrysotile dust in the same animal 1 species The lesions encountered in the lungs of hamsters more than seven months after the initial intratracheal injection of brake dust which are minimal tend to substantiate the short findings in the lungs of rats injected with the same dust Further data on the pathogenic potential of brake dust will be forthcoming when the rats presently on test will be killed and their lungs studied ' microscopically Comment The data obtained from this preliminary study indicate that Thomson was probably correct in his surmise that brake dust was a source for the ferruginous bodies found in the lungs of urban dwellers It is questionable however that Thomson's designation of them as asbestos bodies was proper during the process of production of the brake linings and dust the amount of heat to which the asbestos fibera were subjected is thought to have been such that they lost the water of hydration characteristic of the chrysotile molecule Regardless of what same is given to the ferruginous bodies induced in lungs by the presence of brake dust they are morphologically indistinguish- able from asbestos bodies Because of this fact brake dust would be suspect as having the same pathogenic potential as asbestos The preliminary information developed in this study would however tend to lessen the justification BRAUN DER EH 171-4 11/24/81 11/24/1781-14 GIC 027341063 02730410643 02730410643 02730410643 INDUSTRIAL HYGIENE FOUNDATION OF AMERICA INC 4. for this suspicion Nevertheless the existence of this suspicion makes a more extensive and thorough investigation highly advisable in the interest of the industry Testing the hypothesis based on the preliminary findings described in this report appears mandatory Results if substantiated will certainly merit consideration for publication in the professional literature References 1. Gross P. and deTreville A. Experimental Asbestosis - Studies on the Progressiveness of the Pulmonary Fibrosis Caused by Chrysotile Dust Arch Env Health To be published Gross P. and Brieger H. Silicotic Bronchiolitis Obliterans A Focal Clearance failure Arch Env Health 12 5-9 1966 Gross P. et al The Effects of a Synthetic Ceramic Fiber Dust Upon the Lungs of Rats Arch Ind Health 13 161 1616 956 Gross P. al Experimental Tuberculopneumoconiosis A.M.A. Arch Ind Health 19 320-334 1959 Asbestos Thomson J. G. et al 37 77 1963 as Modern Urban Hasard S. Afr Med J. 00010410644 00010410644 00010410644 001041064 Fig 1 left At the top of the picture there are portions of two alveolar ducts - that show cellular thickening of the walls with involvement of scattered alveoli Alveolar involvement is strictly limited it consists solely of proliferated cells filling alveolar lumens Of additional significance is the fact that elsewhere the lung tissue appears essentially normal although an unusually large number of free alveolar macrophages are present From rat killed 4 days after an intratracheal injection of mg brake drum dust H. & E. x150 right The same field as on the left after the section had been decolorized and impregnated with silver shows stromal proliferation that parallels the cellular proliferation and is strictly limited to the x150 involved alveoli [rw -- -- 4/24/8 141-4- we erm ae ee we mete mee ew Fig 2 left This field shows a respiratory bronchiole dividing into two alveolar ducts There is focal cellular mural thickening that extends into a few evaginating alveoli There is some increased cellularity of surrounding alveoli with an increase in the number of free macro- phages H. & E. x150 right The same field as on the left after the section had been decolorized and impregnated with silver shows occlusive stromal proliferation involving only a few alveoli There is also arborescence of the argyrophilic mural stroma related to increased cellularity of the alveolar walls which past experience has shown to be completely reversible x150 BRAUN Dag Ers11-4 , / 4/24/81 00010410635 INDUSTRIAL HYGIENE FOUNDATION OF AMERICA MELLON INSTITUTE 4400 FIFTH AVENUE Pittsburgh Pa 15213 MEMO TO Dr. Robert T. P. deTreville FROM Dr. Paul Gross DATE RE June 1 1967 Preliminary Study on Brake Dust A report submitted to Manville Corporation of a Preliminary Study of Brake Dust Comparative Pathogenicity dated February 14 1967 indicated that brake dust caused an early reaction of lung tissue of the kind provoked by dusts that are classified as biologically inert The present report confirms the findings of the previous one and also covers important observations on extensions of this study Of primary interest to the asbestos industry is the finding that inhaled brake dust is indeed capable of causing the lung to produce ferruginous bodies that are with the optical microscope indistinguishable from asbestos bodies and in spite of this fact the dust does not have the fibrogenic potential of asbestos dust as judged by the lung's response to the dust as long as seven and half months after its introduction into the lung The asbestos industry should be interested to know whether this lack of fibrogenic potential of brake dust can be substantiated A more comprehensive study would be required which will involve several species of animals and the introduction of the dust into the lungs not only by intratracheal injection but also by inhalation It is probably of equal if not greater importance to the industry to know if the brake dust has the cancerogenic potential that has been associated with asbestos dust In the report of February 14 1967 there is an outline of Recommendations for Future Studies These recommendations require modification AN ASSOCIATION OF INDUSTRIES FOR THE ADVANCEMENT OF HEALTHFUL WORKING CONDITIONS 17-1-3 3333 + BRAUN Dap DIREN 171-11-33171-11-33 4/24/18 4/24/18 L 0 04106304106 636 0410636 INDUSTRIAL HYGIENE FOUNDATION OF AMERICA 2 because they were based on the assumption that free brake dust would be available in practically unlimited supply We have since been in- formed to the contrary With the amount of available brake dust very limited the in- halation technique requires redesigning in order to allow recirculation of the dust with minimal loss PG sjc -- -- ----, DER -- -- ----,-- 171-41- { 3. 1/24/01 1/24/01 ff MANVILLE RESEARCH & ENGINEERING CENTER P.O. BOX 159 MANVILLE NEW JERSEY TELEPHONE 201 RANDOLPH 2-9000 JM Af ft er: 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 a ne samples I am sending under separate cover two of synthetic chrysotile for use in your research These samples were prepared by Dr. Julie Yang of our ok laboratory The sample labeled Synthetic Chrysotile is the purest material we have been able to synthesize The impurities which are present see attached table of properties were probably contaminants in the magnesium hydroxide used . fF as a raw material It is unfortunate fibrils but this requires the use of wanted impurities into the system that we were not able to grow longer a mineralizer which would introduce un- ot ne od in The sample labeled containing Synthetic Chrysotile contains 2.2 per cent nickel The nickel is most probably the divalent form and substituted for the magnesium in the chrysotile lattice are attached Electron micrographs of both samples- 9 va eet Very truly yours mac Attachment James P. Leineweber Chief Basic Chemistry Research Section - 7 : RS PRODUCED ATTACHMENT 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 0.018 Ca Fe Cr 0.017 Cu Ni Synthetic Chrysotile Chrysotile Fibrous Up to 2 microns 12.7 0.02 0.14 0.06 0.06 - 0.10 2.2 Concentrations reported as element not oxides 01204106 01204106 012406 001204106 001204106 001204106 3 4 Mr. Hugh M Jackson Director Industrial Relations & Management * _ Development Manville Corporation 22 East 40th Street New York New York 10016 Dear Hugh Per your telephone instructions yesterday enclosed are reports on the Coalinga and Brake Dust Studies Final reports on both studies will be made in about a year following death and histopathological studies of the animals still under observation No further charges are anticipated | by Dr. Gross with regard to these preliminary investigations An invoice | in the full amount for the Coalinga Study is enclosed A statement for the Brake Dust Study is also attached Obtaining support from industry for the more comprehensive study of brake dust is now our most important concern as Dr. Gross is prepared to go ahead as soon as such a commitment is received He would like to start injections intratracheally at once and redesign of our inhalation technique to conserve available dust should also begin without delay Dr. Gross hopes to report his preliminary findings at the Antigua Meeting in November if Manville has objection It will be mutually advantageous to be able to indicate the follow studies are well under way by then and whether they seem to substantiate the earlier findings regarding inertness Please call if there should be any questions As mentioned your participation in the meeting of the Foundation's Board of Trustees was most helpful and was appreciated by all of us I look forward to our continued association in the work of the Foundation Sincerely yours deT sje Enclosures Mr. Sheckler Robert T. P. deTreville M. Managing Director -------- --E -- 171-4- Me wi et H. M. Jackson - DHQ TO Research and Engineering Center We June 30 1967 a gpee File 259 .% Industrial Hygiene Foundation of America Fibrous Dust Study a Inc. Attached are comments from Sid Speil and Jim Leineweber on the Industrial Hygiene Foundation prospectus for An Investigation of a The specificity of Asbestos Bodies and b The Biologic Effects of Trace Substances Associated with Chrysotile Asbestos dated June 1 1966 Perhaps we can discuss some of these July 6 when Paul Gross visits the laboratory o < - F. L. Pundsack ae Enc CC Speil S. nd J. P. Leineweber E. M. Fenner -Enc . Att C. L. Sheckler received a copy of the prospectus PRODUCED- 5 PRODUCED