Document OzxODjgZN4vr91Kdpq0xJ5Mk1

File Name Industrial Hygiene Foundation of America: Brake-Drum Dust Testing Scanned ? yes Source JMA: S704 Start Year 1967 Stop Year 1967 Contents report Notes INDUSTRIAL HYGIENE FOUNDATION OF AMERICA, INC, Mellon Institute, 4400 Fifth Avenue Pittsburgh, Pa iS2ia Report on PRELIMINARY STUDY OF BRAKE-DRUM DUST: COMPARATIVE PATHOGENICITY for JOHNS-MANVILLE CORPORATION by Paul Gross, M.D. Director of Research Laboratory February 14, 1967 Robert T. P. deTreville, M.D. Managing Director AM ASSOCIATION V >N*UTftiE TO* TMC ADVANOfiMCNT r HCALTHrVi. WOMUMO 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-Man* ville Corporation, a preliminary study of the pathogenicity of "brake-drum 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-day 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,the reactions caused by both, kaolin and brake-drum dust, were also similar to one another and were of the so-called "biologically inert" type. This reaction consisted essentially of the accumulation within scattered alveoli of scavenger cells filled with the respective INDUSTRIAL HYOISNS 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. Tentativelyi therefore, the brake*drum dust tested should be categorized as "biologically inert. ,T Recommendations for Further Studies A proposal for further investigation of the pathogenicity of brake-drum dust has been prepared at the request of Johns*Manville Corporation. Analytical laboratories at Johns-Manville Corporation have reportedly been unsuccessful in identifying asbestos fibers in brake*drum dust and the Industrial Hygiene Foun dation'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-drum 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/m*, the other 10 serving as controls. This con centration would be produced in an 81 x 81 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-year period of research. The cost would be $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 two-year study would cost $75, 000: $25, 000 the first year and $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 the first year, and $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. 37:77-81, 1963. INDUSTRIAL HYOIENE FOUNDATION OF AMERICA. INC 4. Tentative Outline of Brake -Drum Dust Investigation A. Intratracheal Injection ($75, 000) a. 20 Guinea Pigs b. 20 Rats c. 20 Hamsters d. 20 Mice J \ / ) Single injection of near-maximal dose tolerated without death. Pastured for one year and killed. B. Inhalation ($200,000) a. 40 Guinea Pig b. 40 Rats c. 40 Hamsters d. 40 Mice 8`x8* x 8* chamber Wright dust-feed dispersion (at least two needed). Two-year exposure. Concentration^ 100 mg/m*. One-year exposure for mice because of shorter life expectancy. Two-year exposure for others. Six-month holding period. Six months for processing and writing report. Total: Three-Year Study Cost: $275,000 JA ! 0649 COPY INDUSTRIAL HYGIENE FOUNDATION OF AMERICA. INC. MCWUON INSTITUTE, 4400 FIFTH AVENUE Pittsburgh, Pa tsaia PRELIMINARY INVESTIGATION si tbs PULMONARY HAZARD CREATED BY BRAKE-DRUM DUST tor JOHNS-MANYILLE CORPORATION fry PAUL GROSS* U.D. Director of Raasarcb Laboratory May 1*7 0 1 J !J A I 0 6 A 0 INDUSTRIAL MYSJENC FOUNDATION F AMCft'CA. INC, I?OB(rN brake* drum duit |i Itttlt lees than 1 gm) vii obuiaid from Dr. Kenneth W. ieiltb. Portions of this doit wtr tttpndd in vitii e that 1 ml MoUlMd 3. I mg. Tkt Uvuti|i(Lcii ii divided iaio two CMapcatoti* a ihorUkanr. itady and mi of longer daritioa. 1. Short* Torn. Studr: The purpose of this study oti to comport the pulmonary UiiOBi produced by tbli dock la rott with those prodneed ta rote by other docto whose pathogenic potoatUl U well known or le documented. These dusts Included chryeotiU, quarts, aluminum silicate, aod silicon carbide. The differed dost lesions were all produced bf the same intratracheal dotage aad wore all of the tame age (4 daft). Groups of four rate oath wsro injected latratracheally with 3. $ mg of the above dusts respectively, including the brske*drum dust. Resultss As can be eeea la Figs. 1 aad 1 the pulmonary reaction to brake* drum dust Is essedUlly limited to e few of the alveoli evaginating off respiratory bronchioles and adjoining alveolar daots. This reaction consists of cellular pro* liferaties with a concemmitaat elaboration of supporting argyophilic stroma, thereby causing some mural thickening and the obliteration of n few scattered alveoli, la contract to the lesions produced by ehrysotUe*1* sad quarts dusts, *** the inflammatory discs did not extcad into the lamea of the alveolar du*ts or bronchioles, nor were more Ann a few of the evaginating alveoli affected. Indeed, the pulmonary recctlon caused by brako*drmm dust ai this time mere closely rcsombles that produced by nlamtaum silicate and silicon carbide, both of which have been demonstrated to belong la tie noa-fibrogcoic category. J 4i364| INDUSTRIAL. HYQlCNK FOUNDATION OF AMERICA. iNC. XL Longer-Term Study: The purpee e of this study wee to determine (4) if ferruginoue bodies were formed in response to the presence of tbie duet end (b) if the chorecter of the pulmonary reeponee would continue to be u mild ee eeema to have been indicated by the four-day lesion* For there purposes, both rate and hemetere were employed. Twelve hemetere were injected intratracheally on three different occeeione with 3. $ mg of brake-drum duet* Three of theee were killed for eampUag 7 1/2 monthe after the injection* Lung weehinge were obteined from theee enimele using e modified LeBelle end Brieger technique* The eedimente from two were emeered on glees elides end the sediment of the third animal was processed for electron microecopy end electron diffraction study* The lungs were processed for microscopic study* Ten rate were also injected intratracheally with 3*5 mg of brake-drum dust from Johns-Menville, and held for additional injections and longer survival* Results*. Smears of the sediment from the lung washings of the hamsters stowed large somber 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, stow minimal involvemsnt of the parenchyma* The change) are limited to enattered respiratory bronchioles* These show focal cellular thick* ing of their walls and occlusion of a few of thslr evaginating alveoli by prollfcreted cells, macrophages* and occasionally also, by a foreign-body-type giant cell* In an occasional involved alveolus black pigment is present* There is no evidence of collagen formation and, significantly* the lumens of the effected reepiratory bronchi dee ere widely patent* Furthermore, it should ao Ai 06AZ >*UT*1AU HVOltMK FOUNDATION OF AMKR1CA INC. kt mpb0ls^ tkftt MCipt for a fiv of tbi alveoli tvi|lBitta| off nmt of th respiratory br6icUoii the alveolar 11mm appears MtnoL This mlilffiftl dog roo of Involvement lacMtUtid io bamiltri tajectsd takntncbftlly with bnkdnm 4wt stands to ilriktof contrast to the dUfaae, severe, ftod ffttol pMVriABiUi eauSod toy chrysolite dost to lb seme animal species, ^ The lesions iMomlind la tho lugs of biaiton mort than seven KMlhi ftftr the initial tolrtlruhal tojKlloa of brake-drum duit, which ore minimal, toad bo itibitoalUto Ibi short-term findings la the loogc of role Infected with the same dost, fulbr doto oo the pathogenic potential of brake-drum duet will too forthcoming whoa the rate presently oa toot will too killed oad their Image studied microscopically, * Comment: The dote obtained from this preliminary study iadieote that Thomson was probably correct la hie surmls* that brake-drum dost was a source for the ferruginous bodies found in the longs of urban dwellers,^ ft Is questionable, however, that Thomson's designation of thorn as *`asbestos" bodies was proper; daring the process of production of the brake linings and dust, the amount ef heat to which the aabetteft fibers wore subjected is thought to hare boon Such that they lost the water of hydration charaderiatic of the chrysotile molecule. Hogardlees of what name la given to the ferruginous bodies iaducsd in lungs by the presence of brake-drum dust, they aro morphologically Indistinguiaham# from asbestos bodies* Because of this fact, brake-drum dust would be suspect as having the same pathogenic potential as asbestos. Tbs preliminary information developed in this study would, however, tend to lessen the justification J O 4 I 0 64 3 INDUSTRIAL MYQIENE FOUNDATION OF AMERICA INC. for Ihis suspicion. Nevertheless. lbs existence of tkU mipleioB makes a more extensive and thorough love*ligation highly advisable In the Intoroat of tho industry. Tooting tho hypothesis bas'd on tho preliminary findingo doocrlhod in thio roport oppooro mandatory. Results, if substantiated* will certainly merit consideration for publication in tho professional literature* Referoneas 1* Gross, P. end doTrevillOt R.T.P. I Experimental Asbestcsls Studies on tho Progrosslvo&oss of tho Pulmonary fibrosis Cousod by ChrysotUo Poet* Arch. Eav. Hoe1th. To bo published. 2. Orost* P. end Briefer* H* Silicotic Bronchiolitis Obliterans i A foal Cloo runeo failure. Arch, fov, Health, U, M (29ii) 1. Gross* P. ot oil Tho Effects of e Synthetic Coruznie fiber Dust Upon tho Lungs of Bets. Arch. lad. He*lib* 13. 161-164 (1956) 4. Gross. P. ot oil Experimental Tuberculop&eumoconioSis, A. 14.A. Arch. Ind. Health* 320-334 (1059) 3. Thomson* 7. O. ot alt Asbestos us Modern Urban Kaaard, $. Air. Mod. J. 37. 77 (1963) J i i '1 A I 0 6 4 4 Fig. 1 left: ' At the top of the picture there ere 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 a rat killed 4 days after an Intratracheal injection of 35 mg brake drum dust. H. & E. x)50 right; The same field as on the left* after the section had been decolorized and impregnated with silver, shows stromal proliferation that parallels the c ellular proliferation and is strictly limited to the involved alveoli, xl50 0 'J 'i ; 0 4 10 6 4 5 Fig. Z left: This field shows a respiratory bronchiole dividing into two alveolar ducts. There is focal cellular mural thickening that extends into a few evaginating alveoJi. There is some increased cellularity oi surrounding alveoli with an increase in the number of free macro phages. H. Sc . xlSO 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 arhuressence of the argyrophilic mural stroma related to increased celluiarity oi the alveolar walls, which past experience has shown to be completely reversible, xl 50 t > J J ; -J 4 I 0 6 J 5 INDUSTRIAL HYGIENE FOUNDATION OF AMERICA, INC. Mellon Institute, 4400 Fifth Avenue Rittssuroh. Pa. isasa MEMO TO: Dr. Robert T. F. deTreville FROM: Dr. Paul Gross DATE: June 1, 1967 RE: Preliminary Study on Brake-Drum Duet A report submitted to Johns-Manville Corporation of a "Preliminary Study of Brake-Drum Duet: Comparative Pathogenicity11 dated February 14, 1967, indicated that brake-drum dust caused an early reaction of lung tissue of the kind provoked by dusts that are classified as biologically "inert.11 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-drum 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 poten tial of asbestos dust as judged by the lung's response to the dust as long as seven and one-half months after its introduction into the lung. The asbestos industry should be interested to know whether this lack of fibrogenic potential of brake-drum dust can be substantiated. A more com prehensive 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-drum dust has the cancerogenic potential that has been associated with asbestos dust. In the report of February 14, 1967, there is an outline of "Recommen dations for Future Studies. " These recommendations require modification AN ASSOCIATION or INDUSTRIES rOR T*C ADVANCEMENT MeALTHrg^VWORKIha CONDITIONS JO.#* `l/XO'f J? J0 0A I 06d6 IN0U9TBIAL HY01ENE FOUNDATION OF AMERICA,INC. because they were based on the assumption that iron-free brake-drum dust would be available in practically unlimited supply. We have since been in formed to the contrary. With the amount of available brake-drum dust very limited, the in halation technique requires redesigning in order to allow recirculation of the dust with minimal loss. PG:sjc 4 Johns-Manville RESEARCH & ENGINEERING CENTER P.O. BOX 159 * MANVIU6, NEW JERSEY TElEPHONE; {201] RANDOLPH 2-9000 April 12, 1967 Dr* Paul Gross Director of Research Laboratory Industrial Hygiene Foundation of America, Inc. Mellon Institute 4-400 Fifth Avenue Pittsburgh, Pennsylvania 15213 .* Dear Dr* Gross: - I am sending, under separate cover, two samples of synthetic chrysotile for use in your research. These samples vere 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 table of properties) vere probably contaminants in the magnesium hydroxide used as a raw material. It is unfortunate that we were not able to grow longer fibrils, but this requires the use of a mineralizer which would introduce unwanted impurities into the system. . The sample labeled "Ni-containing Synthetic Chrysotile11 contains 2.2 per cent nickel. The nickel Is most probably in the divalent form and substituted for the magnesium in the chrysotile, lattice. Electron micrographs of both samples are attached. - Very truly yours, mac Attachment James P. Lelneveber, Chief Basic Chemistry Research Section PRODUCE! Jlittt . fi? f IT' ' ATTACHMENT Synthetic Chrysotile X-ray Diffraction Electron Micrographs A. Morphology B. SUe Ignition Doss % 1800F Impurities* by Emission Spectrograph A1 Ca Fe Cr Cu Ni Cbrysotile . Fibrous Up to 5 microns 13-2* 0.018* 0.18* 0.017* -- -- , -- Synthetic Ni-Chrysotile Chrysotile Fibrous Up to 2 microns 12.7* . 0.02 0.14 0.08 0.06 0.10 2.2 - # Concentrations reported as element, not oxides producei JM-83 U) I 'J 4 I 0 64 A kr. H|k kt Jackson* OiMttov Industrial RUUmi b Uaaagsmont Dtnlopmtfk Johu*katiUi Corporation 22 Cait 40th fitrsat Haw York, Now York 10014 JunsZ. 1H7 ' Dur Hugh; P#r your tslophoos instructions fivkrdafr snclossd art rsport# on tha Coalings and Braks-Drum Dost Stadias, riul reports on bath stadia* will ba mad* la tbosi a yssr, fallowing daalb and hlstopathologlcal stadias *f tba animals still ondor tbitmltoa. No (trttar ahargss art anticlpatsd by Dr. Cross with rsgard to thasa praliminary tnaastigatlons. An inroica . In tha fall amount far tba Coalings Study is sadoiad. A staiamaal far ths Braks-Drum Dost Study is also attscbsd. Obtaining support from Industry for tba mar* comprahaaslvs study af braks-drom dust is now our most important eoncam aa Dr. Gross is pro* parod to go ahasd as soon as suab a commitment is racsirad. Ha would Uka to start injaatioas intrstrscbsally at anas. and radasiga of our inhalation tschniqoo to ttattm auailabla dust should also bsgSn without dslay. Dr. Cross bopas to rapart his prsliminary findings at tbs Antigua blasting in Nommbsr, if lsfoikurillt baa nmobjactioc, It will ba mutually advuntagsous to ba abla to indicats tha follow-up studls# ara wall undar way by than* and wbsthar thay asam to substantial# to# aarliar findings ragarding inertness. Plaasa sail if thors should ba any fwiUoti. As msntionad. your participation in ths masting af tha Foundation's Board of Truatoaa was most helpful and was appraciatad by all af us. 1 look forward to sur continued association in tha work of tha Foundation. Sincerely yours dsTtsje enclosures ce: Dr. Paul Gross Robert T. P. doTraaillo. 24. D. Managing Dirsctor \ V IV S* - Research and Engineering Center June 30, 1967 File 259 H M. Jackson - DHQ Industrial Hygiene Foundation of America, Inc. Fibrous Dust Study 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 , .V' 4J " */* r .vi **& * 4 Associated with Chrysotile Asbestos", dated June 1, 1966. Perhaps we can discuss some of these July 6 when Paul Gross visits the laboratory. * F. L. Pundsack GJV t4 ae Enc. '. CCS SV Speil * J. P. Leineweber E. M. Fenner -Enc. Atts C. L. Sheckler prospectus) -j (received a copy of the n ' ** * V ,,s * w. .. r'K ;\ 73 JM-83