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FILE NAME Corning OC DATE 1952 Jan 30 DOC OC012 DOCUMENT DESCRIPTION Internal Report for Owens Glass Company by the Saranac Laboratory - Investigation Concerning the Capacity of Inhaled Kaylo Dust to Injure the Lung fees ame ce Be. Report te os Pinul Report | INVESTIGATION CONSTANTNG THE CAPACITY OF INHALED KAYLO DISR TO INJTU HER LUE NG to Illincis Glass Company * Toledo Ohio The Saranac Laboratory ' Sarmas Lake New York Jamary 30 1952 Submitted by Arthur J. Vormld E.D. Director The Saranac Laboratory and The Trudeau Foundation - PLAINTIFF'S EXHIBIT OC11F In cooperation withs Thomas M. Durkan N.E. Philip C. Pratt V.D. 4 Edward C.J. Urban M.S.E. Anthony B. Delabent Donald A. Bailey Jinal Report INVESTIGATION CONCERNING THE CAPACITY OF INHALEDa KAYw LO DUST TO INJURE THE LUNG to the Illinois Glass Company The CONFICDONFIDEENTIALNCOTNIFIADELNTIAL January 30 1952 an CONFIDENTIAL Final Report INVESTIGATION CONCERNING THE CAPACITY OF INHALED KAYLO DUST TO INJURE THE LUNG to Illinois Glass Company Toledo Ohio .. by The Saranac Laboratory Saranac Lake New York January 30 1952 . oe @ eee Submitted by ~\ te . Arthur J. Vorwald M.D. - 3 Director The Saranac Laboratory and The Trudeau Foundation ; . In cooperation with Thomas M. Durkan M.E. Philip C. Pratt M.D. Edward C.J. Urban M.8.B. AnthonBy. Delahart Donald A. Bailey 01 034 0002 . Owens Illinois Illinois 1-50 52 INVESTIGATION CONCERNING THE CAPACITY OF INHALED KAYLO DUST TO INJURE THE LUNG I. INTRODUCTION In 1943 the Illinois Glass Company had developed to the pilot plant stage a new industrial product known as Kaylo which could be used as a thermal insulating material and for other applications According to information supplied by the company this product was prepared by beating , under steam pressure a suspension of calcium hydroxide silica and asbestos to form hydrated calcium silicate Studies at The Saranac Laboratory showed that although the principal component of Laylo was the hydrated calcium silicate some unchanged raw materials including asbestos and free silios in the form of quarts or diatomaceous earth were also present in . the final product " Before Kaylo was used commercially on a large scale it was important to determine whether or not any dust liberated from this handling product during manufacture or fabrication would be likely to constitute a respiratory hazard to exposed individuals Therefore a comprehensive investigation was undertaken in which the effect of inhaled Kaylo dust on animals was studied The investigation was started in February 1945 and was carried on for more than five years - It explored the nature of the pulmonary tissus reaction to inhaled Kaylo dust in normal animals and in animals harboring a tuberculous infection In this study final report of the the principal findings given in previous interin reviewed reports will be briefly and the conclusions stated derived from entire experimental program will be the ons - 01 034 0003 Final Report Illinois 1-50-52 II DUSTING MATERIAL USED received in separate shipments as follows 1 Received Lot - - #5 . in January 1945 *" February 1947 January 1949 Saranac representative Laboratory are given in sample of table 1. the material as received at The It will be noted that the only # of Kaylo was than per cent but the quarts content of lots value for minor alterations in composition may occur from time to time in accordance with changes in the raw materials used For example the quarts lot less 1 2 01 034 0004 Final Report Illinois 1-80-62 - B. Ray diffraction studies The ray diffraction pattern of samples of two different shipments of Kaylo are present shown in fig 1. The prominent lines are probably those of a hydrous calcium silicate which is the principal component of Laylo Com- parison of patterns a and b discloses that the quarts Janulainrey b than in a indicating that the Laylo received in is stronger in 1949 has a higher quarts content than has the earlier product received in January 1945 . Faint lines representing calcite and chrysotile are visible in both patterns Diffraction lines produced by mosite are also present in pattern b C. frequency studies The distribution of Kayle dust is shown by the graph in fig 2. The lines of the graph represent the parent in the dust machine and two material sammpalgensification pheric dust collected in the dust room on different days A of atmos of 1200X was used in making the sise frequency counts It will be noted that about 85 per cent of the partioles in the parent material visible at microns that magnification are smaller than 5 in size the corresponding values for the sumples of atmospheric dust are 90 and 95 per cent This difference in the two samples of atmospheric dust which were derived from the the same parent material may have been due | day variation in humidity inside the dust room @ apny . III REVIEW OP PREVIOUS REPORTS eo me During oe 8 oe the course of the investigation reports were issued with Kaylo dust fire interim The first report dated May 13 1946 revealed that in guinea pigs 01 034 0005 Final Report Illinois 1 ., 80-52 . - e. . exposed for 14 months to Kayle dust the tissue remation consisted only of microscopic focal collections of dust cells The associated tuberculous infection had not been altered mough to be of significance significance the second In report issued on October 30 1947 it was noted that there was no evidence suggesting that Kaylo dust when inhaled into the producea pulmonary fibrosis in rats exposed for 18 months or in guinea exposed for 30 months These findings seemed to show Kaylo dust to be lungs pigs t. biologically inert material In the experiment dealing with the effect of the dust on a tuberculous infection the should results that the experiment be repeated - were inconclusive indicating The tions on Contrary third report dated October 80 1948 presented the final observa- the effect of inhaled to previous tentative Kaylo dust on normal uninfected guinea impressions based upon an exposure of pigs 30 . months which suggested Kaylo dust to be inert the study of minals exposed for $ months disclosed that the material is not inert but is capable on prolonged inhalation neither silicosis nor of producing asbestosis in the diffuse fibrosis which guinea pigs is caused by However inhaled diatomaceous earth developed in the exposed animals , 1949 reviewed The fourth report dated April 30 the results of the definitely first 8 months of a new experiment in which the effect of inhaled Kayla , dust on a tuberculous infection in guinea pigs was studied No adverse effect of the dust on the infection during this months period was noted The given in fifth report dated January 1 the fourth report by extending 1950 supplemented the information the observations to infected animals eta 01 034 0006 Meee wes sa w ree eu ve that had been exposed to Kylodust fer poriods up to 14 months The findings at that time suggested that Taylo dust had a slightly adverce influence on the courseof a tuberculeus infection in guineapigs but that infl_uence e d prenounced the offoot was by no means ac - a that of quarts dust - _ ~ se = wwe = oe V i atedind R^ . =_ eeo FENTVERINIASMOENTL VERINISAMO ENTVTERINISMOIWIOTHNZAYLO LUST ad - continuation & =ee of the previous interin reports and as a summary for continuation of this final report reviewof the entire program of study is reported _ In the inhalation experiment Serene Recoratory 30 1917 1100 1104 - Tempe ofof guinea pigs retshoustige vars placed in eutical dust Tempe room 8 feet in dimension in which on twosphatic mumpention of Kaylo dust Es mintained The room was operated for more than five years from y June experiment February1945to 2a ee ee in the About 450 animals were used 1950. | About _ ~ andsome of them lived in the dust rom for as long as 3 years oo _ ~~ tio Conditions ofme The stumspheric suspensioonf Imple dust was createbdy the action of a poddle that rotated insido c hopper lcocted a corner of the dust roc which contained the divided Implo product The inst cloud gonerates in this manner floated out into the room there it was maintained for 8 hour -on five days of the wock and for 4 hours on Saturdays At regular interval during the experiment a few animals are filled and the tires chamined " grossly and microscopicallyto determine the natured natured the extent of the dust reaction The tissus was also analyzed chemically to estimate estimate the amount of Keylo dust retained in the lungs of minle exposed for definite periods of time + ; 5 en oe & eh. Final Report Illinois 1-30-52 - Dust counts of atmospheric samples collected in the dust room with the midget impinger were made regularly The concentration of Kaylo dust to uninfected which the animals were exposed was generally within the range of 100 to 125 million particles per cubic foot of air and the overall average was 115 million In the experiment with infected animals the concentration was higher the average being 205 million B. Exposure of minfected animals Three species guinea pig rat hanster - were employed in this phase summary & of the investigation of the findings is given in table 2 1 Quines piss At the beginning of the experiment 100 minfected guinea pigs were placed in the dust room and 6 months later 25 more were added to replace animals that had died in an pneumonia Since this pneumonia occurred at that time epidemic of acute also in animals exposed to another dust in an adjacent the room unfortunate epidemic was considered accidental in experiments at that Epidemics of this kind which occurred occasionally r'e adnos bon contro Groups of guinea pigs usually 2 to 4 in number were killed at 2 4 6 8 12 18 21 24 33 27 30 and 36 months after the beginning their exposure to Xaylo dust so that the course of the pulmonary reaction could be followed s In guinea pigs exposed for periods to 30 up months there was only a vetiys to - mild tissue response the inhaled Kaylo dust and reaction was limited accumulation mactrhoephages to the of clumps of containing in groups of adjoining air spaces fig 3 The intervening alveolar walls were only slightly thickened by accumulated lymphocytes Cocational multinucleated 01 034 0008 Final Report Illinois 1-30-52 giant cells were visible but there was no excessive proliferation of tissue Histiocytes or deposition of connective tissue A few asbestosis bodies were sem fig 4 Microscopic study of the tracheobronchial lymph nodes which became enlarged but remained soft revealed clusters of inactive dust cells similar to those in the lings but without asbestosis bodies It is point pertinent to out here that animals exposed to asbestos dust for a similar months period exhibit a severe tissue reaction with the production of fibrosis fig 5 For comparison & lung section of a normal guinea pig is shown fig ) for The 9 animals exposed to Kaylo dust for more 55 months and 6 animals for 36 months showed than 30 months 3 animals not only the lesions like those of the months animals but also exhibited a true fibrosis of a type characteristic of the response of guinea pigs to inhaled asbestos fibers This reaction is a rather diffuse type of fibrosis which forms . principally about the bronchioles the mall ducts from which the terminal air spaces or alveoli arise A comparison of fig 7 and fig 5 reveals the similarity of the tissue reaction produced in the lungs by Kaylo dust and by asbestos dust The lesions in between 30 months and the tracheobronchial 56 months lymph nodes ~ showed no change 2 Bag This species was employed because typical nodular fibrosis te more produced by inhaled quartz dust develops rapidly in rats than ocnes were in animals of other species Forty rats used and some of them were - exposed to Isylo dust for as long as 18 months Pneumonia was not a problem during the first year of the experiment but among the rats exposed for 13 to 18 months 16 animals died with terminal bronchiolitis and lobular 01 034 0009 Final Report : Illinois 1-30-52 . AY pneumonia Since laboratory rats older than one year even those not exposed to dust are commonly subject to this type of lesion the high mortality rate is not considered significant In order to follow the progression of the tissue reaction to the inhaled Kaylo dust rats were killed in groups of 4 after 6 9 12 15 and 18 months of exposure It was revealed fig 8 that throughout the experiment the reaction to the dust consisted of focal collections , in the alveoli of macrophages which contained particles and spicules of dust The only change observed as the exposure period became longer was an increase in the number of the alveolar fooi Similar filled macrophages were seen in the tracheobronchial lymph nodes In no animal was there any tissue reaction typical of silicosis The peribronchiolar fibrosis of asbestosis was not discovered though occasion- al asbestosis bodies were observed In view of other experiments with pure_ fibre asbestos dust typical peribronchiolar fibrosis would not be expected in 18 months exposure to Kaylo dust Seer 3 Hamsters Twenty hamsters were placed in the dust room and after 3 9 12 and 18 months of exposure 2 animals were killed at each period for study at the months period 3 animals that died from other causes were examined Histologic examination revealed } that the Kaylo dust fibrosis & accumulated very alowly in the lungs No was zem except in one espe months . hamster which had been exposed for 18 In tchoautld trace of peribronchiolar fibrosis so slight that it animal there was a be definitely recognised only at high magnification present and at the usual sites more Asbestosis bodies in small numbers 01 034 0010 o . . . a Final Report Illinois 1-30-52 C. Exposure of tuberculous animals C There are three types of experiment which are valuable for determini the effect of inhaled dust on the development of tuberculosis in experim animals In the simultaneous infection experiment normal animals are in with attenuated tuberole bacilli by the inhalation method and then are i ately transferred to the dust room Thus the tuberculous disease and ti reaction to the inhaled dust will develop simultaneously In the reacti experiment the mimals after being infected with the tubercle bacilli allowed to live in a clean atmosphere for several months before being ex posed to dust During this period the tuberculous disease generally reg and some healing takes place Following exposure of the animals to some dusts the lesions may continue to regress or with other dusts the tube process may become active and spread The predisposition experiment is C in which animals are exposed to dust for several months are then infect and are immediately returned to the dust room where their exposure to | is continued In this way the effect of a previous dust exposure on th early course of a tuberculous infection can be studied For investigating the effect of inhaled Kaylo dust on the course o tuberculous infection a particular attenuated strain of human tube bacilli known as the R strain was employed This strain has a low o degree of virulence for guinos pigs and in the normal minal produces eonet aa] "* limited disease which will progress for 2 to 3 months and subseque __- heal In an animal which has inhaled quartz dust or certain other toxi dusts however the disease usually progresses continuously and ultima causos the doath of the animal Since experience has indicated that t { . 9 01 03 . Illinois 1-30-52 bacilli of guinea pig the R strain have about the same degree of virulence as tuberole bacilli of the human strain have for man for the it is possible to obtain some correlation between the influence of various dusts on the R tuberculous infection in guinea pigs and the effect of these dusts on a tuberculous disease in industrial workers For infecting the animals with tubercle bacilli an inhalation inhalation technic was used A glass tube was fitted over the animal's nose and into this tube a suspension containing was sprayed with a DeVilbiss a known number of atomizer As the R bacilli of the mimal breathed strain he inhaled the atmospheric suspension of bacilli into the lungs where they became localised 1 Simultaneous infection infection Simultaneous guinea guinea pigs exposure to Kaylo me started infected at the time their infected the time time their their In the first experiment in . which animals were infected with tubercle bacilli at the time that their exposure to Zaylo dust was started table 5 25 guinea pigs were used but an epidemic of pneumonia during the first 10 months reduced to 16 the number of animals available for study Two of these died at 14 months apparently fren progressive tuberculosis but not from tuberculosis In and the 3 others died from undetermined remaining T2 animals the course causes of the tuberculous disease was followed by killing 1 or 2 animals at 1 , 9 12 15 18 and 24 months after infection In 11 of the 12 animals the lesions were isolated encapsulated and regressing in the remaining animal which was killed at 15 butfibrosis had months the lesions wore widespread throughout the been produced which indicated a tendency to heal lung In an attempt to develop a strain of guinea pig resistant to the infection that had caused the pneumonia some of the animals were used for breeding during 7m 01 034 0012 Owens Illinois 1 30 162 30 62 bacilli tubercle whether the infection is combined with dust exposure or in not those animals must be excluded assaying the effect of an inhaled dust upon a tuberculous infection It is believed that sports are mimals whose native resistance to the attenuated R organism is unusually low Support for this belief is given by experience with quarts dust a definitely hazardous material which reactivates an inhalation infection produced by attenuated R extension to bacilli but organs other ordinarily is not associated with tuberculous than the lungs and tracheobronchial lymph nodes The control dusted group table 8 of guinea pigs for this experiment was infected at the same time as the experimental group of animals subsequent- ly dusted The same culture of organisms was used for all animals The tuberculous infection followed its usual course in the control group and resolved in all of the animals except one a sport in which the disease , spread Although a progressive tuberculous disease was noted in 4 guinea pigs of the second experiment the degree of extension of the disease in them was slight The remaining 25 animals 8 of which died of intercurrent pneumonia showed of regression and no spread and healing as in the the infection followed dusted control the natural course animals It is believed therefore that the inhaled Kaylo dust had no significantly adverae effect on the tuberculosis a 2 Reactivation infection guinea pigs after being infected lived x ind o He in clean air for several months before being exposed to Kaylo dust In the reactivation experiment table 4 26 guinea pigs were infected with the attenuated bacilli and allowed to live in a clean atmosphere Animals 12 01 034 0014 Final Report Illinois 1-30-62 this experiment 14 months and the The 2 animals that died from progressive single animal killed at 15 months that tuberculosis at exhibited wide- spread lesions animals in the were all used as breeders during the experiment which wore also employed experiment but 4 other for breeding failed to breeding elament showwas this from conclusions it extensive disease factor of Owing to the of moertainty introduced by and also because of the high mortality from pneumonia considered impossible to establish this experiment definite about the effect of inhaled Kaylo dust upon tuberculosin and therefore the experiment was repeated The simultaneous infepcitgison table 3 with 50 guinea conducted experiment was a second time instead of 25 and animals were killed in pairs for study at 2 4 6 8 12 15 and 24 months after infection Again that cause during 16 months and 24 mfointghs spreading spreading extent the first 8 months of exposure and 2 more during the following Of the remaining 22 guinea pigs 4 animals revealed at 15 23 after infection a tuberculous disease disease of minimal 9 which was confirmed by microscopic examination Three other animals al so had a spreading tubercuTlhoessies extended to the spleen and other organs but in them the disease had animals were considered ex- ceptional and in the past have been classified ore . is given to a guinea pig in which the 10 . as sports The term"sport inhalation infection with the attenuated principally @ bacilli is not confined to the lungs and tracheobronchial lymph nodes but extends also to other organs and produces in them tuberculous changes Since gross of sufficient extent to be recognised in the sports represent a departure from the normal pattern of tissue reaction to attenuated 11 01 034 0013 Illinois 1 30 52 of this group were transferred to the dust room at 2 months 10 animals 4 months 8 animals and 6 months 8 animals after infection In order to follow the course of the tissue reaction a pair of mimals of the first group 2 months in clean air was killed after only 2 months of dust exposure and in addition animals from all groups were killed in paire after 4 8 and 12 months of of the dusted animals failed exposure to to reveal a the dust Examination of the tissus significant reactivation of the tuberculous disease by the inhaled Kaylo dust Only one animal showed evidence of spreading pulmonary tuberculosis minimal in extent fig 10 That animal was 1 of 3 that had lived in clean air for 2 months after in- fection and then had been exposed to the dust for 12 months In the coanntdrol normal manner : group table 4 the tuberculous disease behaved in the healed with the exception that one animal a sport developed a spreading disease and died from tuberculosis & months after infection - 3 Predisposition infection guinea pigs were infected 3 months after their exposure to Kaylo dust was started An experiment of this type is a severe test because a dust that is only very slightly taxis may produce tissue changes which though minor character may be sufficient alter to profoundly the development of a fresh tuberculous infection In this experiment table 5 which was designed to study the effect of Kaylo dust accumulated in the lung upon n developing tuberculous d^>saeo 30 guinea pigs were exposed to the dust for 3 months and then were infected with attenuated tubercle bacilli The dust exposure was immediately resumed and carried on for another 21 months 13 - 01 034 0015 Illinois 1-30-62 During the course of this experiment 5 animals were killed at the end : of the preliminary 3 months .ths olump of dust phagocytes within the .ths alveolar .ths showed spaces Of only an occasional the dusted and infected animals 7 died from intercurrent pneumonia which eliminates them for purposes of analysis 1 animal died at 14 months after infection from spreading tuberculosis and the remaining pairs at 2 4 6 8 10 12 and 16 months and 17 animals were 8 were killed at killed in 21 months after infection tubercles Of the latter group of 17 animals 1 showed many spreading 10 revealed scattered spreading tubercles and 6 exhibited healed tubercles These findings indicate that a tuberculous infection in guines originates pige that to Kaylo durt was several months after a prolonged exposure of the animals initiated may be unfavorably influenced by the inhaled dust This influenos however is minimal in degree The tuberculous infection in the control mimals table 5 in general regressed and healed Of the control mimals there was as usual 1 sport coattered animal killed 10 months after infection which revealed a few isolated tubercles that were of the spreading type D. Analysis of tissue of exposed animals + Chemical analysis of the lungs of uninfected guinea pigs that had yielded data inhaled Kaylo dust for periods up to 36 months the reported tbete . in table 6. It will be noted that as the period of exposure became longer we the ash values gradually increased thus showing that mineral matter was oe. accumulating in the lungs There was a pronounced increase silica and then in the component up to about 30 months a slight decrease Thereason for 14 01 034 0016 * ose Illinois ~ Illinois 1-80-52 this condition which has been observed in experiments with other dusts is . not entirely clear but it seems to be due in part to dilution of the inhaled dust with the inorganic components mobilized as a result of the increased tissue reaction which developed as already mentioned in the guinea pigs between 50 and 56 months of exposure to Kaylo dust Since only 2 minals were analysed for each exposure period individual values occasionally were out of line but the general trend was clearly indicated T. REVIEW OF EXPERIMENTAL FINDINGS The findings derived from the various inhalation experiments will be reviewed briefly and some points of significance mentimed A. FindinFginsdings for normal animals inhaling KayKloaylo dust The results of the inhalation experiment prove that Kaylo dust aben inhaled into the lungs of guinea pigs for a prolonged period 50 to 6 months is capable of producing the peribronchiolar fibrosis characteristic of the disease asbestosis No fibrosis was formed by the inhaled dust in rats or in hamsters with the exception that fibrosis was barely recognizable in a single hamster exposed for 18 months In animals exposed for 30 months or less the lesions showed no fibrosis but certain aspects of the lesions although masked by the reaction to the inert components in Kaylo dust were etre! of compatible with an early stage in the development development e asbestosis a disease in which there is a predilection of the fibers to localize in the terminal : : bronchioles is initially This behavior is deposited chiefly unlike in the that of particulate alveoli rather than material which in the lumens of - 15 01 034 0017 Final Report . Illinois 1-30-52 -- the bronchioles great deal of it Since lodged the major portion of Kaylo dust in the alveoli and the reaction is particulate overshadowed the developing peribronchiolar response to the asbestos fibers of Kaylo It was noted that in the region of the bronchioles of for less than 60 months there was evidence of more is usual in the reaction to an inert dust Little animals which were exposed dust cell activity than significance was attached to this observation at first however because there was no indication of reaction fibrosis The early to Keylo dust is somewhat different from that to asbestos dust since the particulate components modify the of lesion recognizedtype In silicosia modification of the lesions is a condition containing which follows the inhalation of a mixed dust quarts and certain inert material such as iron oxide The rate of pneumonia among the animals exposed to Kaylo dust was unusually high Since the pneumonia rate has bem elevated also in several inhalation experiments conducted with asbestos dust it is possible that the asbestos component of Kaylo may have an unfavorable influence on the incidence of pneumonia Verification of this possibility must wait further study While the experimental investigation proved that Kaylo dust is capable of producing asbestosis the results showed that the dust will not cause animals silicosis in animals of the three species tested In none of the @: 40ers there bee even those exposed for the full year period was any focus of the byclinsmodular fibrosis characteristic of dilicosis A study of the exposed _ _ ee. animal's disclosed which follows the diffuse also that Kaylo dust did not produce the fibrosis inhalation of diatomaceous earth In regard to the hydrated 18= 01 034 0018 <n Report Owens Illinois 1-50-62 - which be calcium silicate is the major constituent of Kaylo it may said that although there is no specific information about the effect of that compound on pulmonary tissue there is much clinical and experimental evidence to suggest that it is biologically inert Furthermore in the inhalation experiment with Kaylo dust there was no deleterious effect noted attributed which could be to the calcium silicate component of the inhaled material This observation is supported by our studies concerning similar calcium silicates in cement B. Findings for tuberculous animals inhaling Kaylo dust The inhalation experiments in which tuberculous guinea pigs were exposed to Kaylo dust indicate that when the animals were infected with was started attenuated tuberole bacilli at the time exposure to the dust dust or were . infected prior to that time the inhaled Kaylo had little or no unfavorable effect of significance on the tuberculous infection In most of the exposed animals the tuberculous disease healed in a normal manner and in the few animals that exhibited a spreading type of lesion the aggravation of the disease by the dust was minimal O " obete *.+ se Then the mimals inhaled Kaylo dust infected the subsequent accumulation of have a alightly unfavorable influence on disease for the the several months before being dusts in the lungs seemed to tuberculous usual course of the period 1. Kaylo dust when inhaled for a prolonged is capable of producing 17 me 01 034 0019 Owens Illinois Illinois Illinois . 1-20-52 ow in the lungs of guinea pigs but not of rata the peribronchiolar fibrosis typical of asbestosis B. The inhalation of Kaylo dust will not cause in guinea pigs rats or hamsters either silicosis or the diffuse the inhalation of diatomaceous earth fibrosis which sometimes . follows C. The inhalation of Kaylo dust course of tuberculosis in guinea does pigs not significantly influence the usual infected with attenuated tubercle bacilli provided the infection is given to the animals before they are first exposed to the dust In guinea pigs that have inhaled Kaylo dust for several months before being infected a continuation of the appears to have a slightly unfavorable effect on the disease exposure o Pt oer :: :: :: 01 034 0020 om. ~ compere Owens Illinois W Table =i o o . estec om ANALYSIS OF KAYLO : ; Analysis of lot # received in January 1947 Chemical analysis S10 . 43.80 1102 Mn0 O 1480 Nazo 820 Loss * below above 105 105 0.12 0.09 24.94 7.20 0.17 0.15 4.52 15.29 99.74 Petrographic and ray diffraction analysis The material consisted principally of clay n sen which produced a definite ray diffraction pattern presumably that of a hydrous calcium silicate Quartz particles up to 30 migrons in size were present but they were not numerous and by weight probably made up less than 1 per cent of th sample About 6 per cent of the material was calcite and approximately 16 to 20 per cent was chrysotile or serpentine which was largely fibrous The fibers and bundles presont were usually several millimeters in length and were seldom shorter than 0.5 millimeter 01 034 0021 Final Report Illinois 2-50-52 Table 2 SUMMARY OF INHALATION EXPERIMENT WITH KAYLO DUST Exposure of Uninfected Animals Nature of Experiment Animals used f 125 g pigs Uninfected animals exposed continuously to Kaylo dust until death - 40 rats ho ot er o 8 4s 20 hamsters Maximum duration of exposure to Kaylo dust months 36 18 18 Results Peribronchiolar fibrosis like that of asbestosia produced after 86 months of exposure At so months of exposure reaction was limited to accumulation of clumps of containing macrophages without fibrosis A few asbestosis bodies v^reseen Tracheobronchial lymph nodes became enlarged but remained soft and without fibrosis Pocal collections of dust- containing macrophages in the alveoli and in the tracheobronchial lymph nodes Increase in number of focal collections was the only change observed as exposure period became longer No silicosis or asbestosis Dust accumulated very slowly No fibrosis except in one animal which showed very slight fibrous reaction after 18 months of exposure Asbestosis bodies in small number and at usual sites 01 034 0022 Table 3 Pinal Report Illinois 1-30-52 SUMMARY OF INHALATION EXPERIMENT WITH KAYLO DUST Exposure of Infected Animals Simultaneous infection phase Nature of experiment Animals used Animals infected with tuberole bacilli at beginning of exposure to Kaylo dust : 25 pigs Controls to * infection no exposure to dust 26 E. pigs Animals infected with tuberole bacilli at begiming of exposure to Kaylo dust | Repetition of previous experiment 30 6. pigs Controls to Te infection no . exposure to PeRy dust 34 B. pigs Maximum duration af exposure to Kaylo dust. months Results 24 0 24 Ct 9 Results inconclusive adverse influence of Kaylo dust on a tuberculous infection not defi- nitely established Progressive disease in 3 animals that had been used as breeders . Infection followed usual course no spreading disease No pneumonia Little or no significantly adverse effect of inhaled Kaylo dust on a tuberoulous infection was demonstrated Confirmed spreads all of slight degres in 4 of 27 exposed animals the other 3 exposed animals were sports ae oo Infection followed usual course no spreading disease except in 1 sport - The guinea pigs were infected with tubercle bacilli of the virulent R strain 01 034 0023 i Table 4 Illinois 1-30-62 SUMMARY OF INHALATION EXPERIMENT WITH KAYLO DUST Exposure of Infected Animals Reactivation phase Nature of experiment Animale used Animals infected with tubercle bacilli and then left in clean air for the following periods before being exposed to dust 2 months 10 8. pige 4 months 8 6 months 8 Controls to 34 infection no exposure to dust Maximum duration of exposure to Iaylo dust months 12 12 12 fe] Results No definite evidence of reactivation of the tuberculous infection except in 1 animal exposed to Kaylo dust for 12 months that had a slight spread of the disease No definite evidence of reactivation ~ No definite evidence of reactivation Infection followed its usual course and resolved in all animals except me a sport in which the disease spread to other organs and caused the death of the animal 6 months . after infection The guinea pigs were infected with tubercle bacilli of the virulent R strain 01 034 0024 I r -~ - ( ; , . . Final Report Illinois 1-30-82 i Table 6 SUMMARY OF INHALATION EXPERIMENT WITH KAYLO DUST Exposure of Animals That Ware Infected 3 Months After Their Exposure to Kaylo Dust Was Started Nature of experiment Animals exposed to Kaylo dust for 3 months then infected with tubercle bacilli and the exposure to dust continued Animals used vrimm duration of exposure to Kaylo dust Results . months 30 g pigs S | before plus infect Spreading disease in 1 | animal killed 2 months after infection and in 2 animals dying 14 months after infection 21 . after infect Controls to 25 .0 infection 8. piga no exposure to dust Infection followed its usual course and resolved with the exception that 1 minal 10 months after _| killed killed infection showed scattered isolated spreading tubercles m a oe The guinea pigs were infected with tubercle bacilli of the virulentR strain 01 034 0025 Minoral Table Amount Period (% (% (% WwW of ; Table of DUST . ash) . of UNIFECTD . PIGS of KAYLO WITH ANLYSE UNIFECTDdust . continuous continuos | exposure to 5102 2an MgO |: Cad ; 88 DUSTdeath 18 24. . 1,62 1.69 1.23 1,05 4.06 6.57. x 0.07 0.06 % % 0.24 eo: e (Exposure 30 4.04 4.42 a 2 OF 5.62 achi achi tisue ) $.42 6,87 4.42 4.47 4.154.15 4.59 4.59 LUNGS 4,88 4.90 6.18 . 8.23 4.71 4,78 5. 5 0.31 2,19 8,00 2,68 2,00 6.366,05 0,08 0,08 0,10.0,08 0,20 0,26 5,74:4,25 ## < OF to 1. 0 componetscomponets components' 102 6,04 0.24 0.22 0.25 0.25 0.31 0.63 0.630.59 0.84 0.66 0.46 0.69 1.12 \ dried tisue tisue' CQO 10,12 " 0.080.09 0.080.08 0,13 0,13 0,S14 0.09 0.19 0.13 0.14 0.13 0.14 1,604,66 3,172,00 10,25 10,60 0.06 0.08 0.100.10 0.11 0.11 0.16 0.20 0.06 0.18 0.11 0.12 6,66 6,52 2,061,83 MgO 12,27 0.080.08 0.08 0.08 0.11 0.11 0.08 0.32 0.32 0.06 0.05 2 6.05 6.046.04 componentscomponents componets3,68 910212,64 ash 1,20 2.92 2,66 12,62 12,70 6.67 4,87 6.05 4.06 4.42 6.36 6.36 , 12.27 10.80 12.27 12,70 12.54 17.65 15.93 19.66 17,10 20.25 - 2,8017.65 Kk 2.54 0.55 2.56 . 3,08 3,76 2.412,67 0,56 15,03 1.281.89 2.682.68 2.43 2.43 . 3.173.17 2,06 27 2,1 i* 0:20,02 2/262,66 ugo 19,6 1.62 1.09 2,192,192.002,43 2,43 1.60 6.66 1.72 3.17 2,1 3.263,77 2 262,26 1.0 17,10 0.170,22 0.220.13 ' 0.69 0,07 8.586,70 ; s "9,2 838 1-30.52 YS. 2,38 3.17 5.282,062,122,89 12.45 15,10 0,3"0,170.19. 0.11 0 10,6540,67 0,86 6,4586.36 6.65 01 034 0026 Finai Aspor Illinois 1-30-52 Principal chrysotilo line Principal auartz: line calcit '" rincipa1 on ~~ Principal calcito lino riuc uz " Principal chrysotilo lins siz, 1 RAY DETONPACTION PATTERN OF ZAKO 2. Kaylo duct received in January 1945 %, Taglo dust received {n January 1949. Both patterns contain lines which representadorato representadorato representadorato amount of chrysocile and of caloits and a mall amount of quarts Faint lines representing what is probably the Irydrous calcium silicate compment of Keylo are also .prosaut .prosaut both .prosaut .prosaut addition Storigizs? 24in of pvctiss ) contatine a yorz wrale Liz sory sspondins to " ' " '" .n .n .n .n The quarts content indicated by pattern a is less than 1 per cont . ote cm mee . eo. : at mew en Cow, coms 01 034 0027 wer a eo e e a @ e asi 1 . L BENNIN BENNINBENNIN i BEN IN , : A . A ies iT} cf. 7 5 byra T ey TUT1 ests 1nit name L Le (DESE mas wn ye ABE SDS! bo ac phases Li QUIMIGNAPHING i | , , QUIMIGNAPH ING ihQUfIMIGNAvPQHUIMHGNAPHItNGNG ay ny pat Narn + ra O LW Pp war bee hang 4 Sat .. i i Tout FERMOPATIJ FERMOPATIJ FERMOPATIJ NINAH NINAH mm Dan mem a ai p aue paar u 4130 ER fit NINAH 13 bd * NINAH NINAHNIAHNINAH 1 rt : 3 ~ thi: Tat bd 815 STH + U z lf . v oa. mabe 7U9 91 al La a4 pe ht 2 tr ; ' ofa q 7o)H HT IT) {I}. ye oetledg ele phogte tH DEE Us art us Hh 1 b. : 4 Lal ue +t 3 yen Th dnens a! I LJ. dowd i . ry Lee j y o-tat> pam : y sf j <b bano 43 4 * it | ' ^' 25 Low } a T | z pa | 4 ref a pene a bs v BS = T bp re 3 , rts . 4s HEM HTS ' ipo ras c 91 P ibd is0A : xdad ac, = ot rte &347 LI20e Sew sale at : t ium el x bb + s t = 4 Z vee tM 1 - = = sS + I vt Poy rs ZUINIII ee | ree | psp he ZUINIIIrt e 21. - 44 > = ul = am Apts Doret peGet m ads Fe sakpe ps cw Mond bp go ake ae ZUINIII try + ZUINIII r t + .-won wind ty ap vot teas hb a whe gece Ss be ann ws aro Bn Ee a - - ee spelakat a sr on hooves ond Be od 6.5 es aime . 7 rt +} to stpcom} 40 Ty bd J wpm bute wnaa ? = 5 rp = os 1025 06 of T see 4S:ES ae ad ; oa bob ves prmag ~T Lage] + ete be ba pad tucasahekoonang i amel ZUINIII : + ZUINI I uae ba re deve au ru eas na rus Be : reas T 4 same "Tit og Tr as Swed n +t p aaree on trtt 4 fe 1 et ipeeouug - PBb yl Le areas al be phe 1#y Opa - : ? mal thes 7 + vi yee t c ; S i + tt Terry Los i atm Je a : t ale t ny r . % we dag ~ ni ul . rina! b re RE TP tebed, =< toy) Lit epi po-a il: rl D t * bam 7S i oo f.ee OO - Ser: SOS SIN Gt eeteet Z. ft aay ^' > TEKKINUTULME TEKKINUTULME4 +33 + TEKKINUTULME pe2g po SS EET one ah 5 p oes ape go adkes apart Sa re CSS Kew ore i pas apm |=~: 20s Fas wh am 60} ob same - amhe , * bios = = . * ~ TEK INUTULME = rnpay? hy wirty ya se gs chs0e eel = 1 Serr . 2 dee fa ; . erent UES SI isles Fr one. ~=- CS emarend c L Tr g SeaMoet ue ry + teel-::2 : => bs vs of 3 nn aby > rt -. roy ; . o r; - : wae aH. e < _i1 ~ ELE ay L : * ad ag nya 0: a= & std deethe i mah) ats . TTT 4 ch Bs u 4 cid 19090 atx a i P a Wk *) rf RHP tt LS asa oo e . po 2 fiah bas 5 bs . om H bos eB t ee crpan + fells Or) a sk : ap Walt! S 3 lowe ol .* of Tt o; Fad' i] 3 7 | 4 T =, ue t Se Se A TE IR iF lo abs fy q i " RBGU i!e ON 0 3 oc. OP rate t ca ba! oe Ou . u py <8 ' + = an ae T t+ tay peed s $= = . 5 Ld. tw 2 ied & e ~- . Se on a = peand spaces - T i * be i! * CR 4; + tt 7 dawedtebeete pe pndntne ange co] QP 0 Peed 9 iy cedtueobead td = t t t dd SardthOG oyOE ite! coats 2 oes Pees Oe a On Tt bans boas ans a me erry t on | Se _ tha 0d bo (snat gam os PE Sa . -owpdes 60EGE i dome oe hwy Gud . - e me LE dep Py .o- a t . aa yiep bd L E il ops: = Pott == rE 3 palmre3r xF p3- = 5e- derah hwes . oe =F Fr < . : - bo 2 r $ Pomk oe . Pe at ae OR ee dD _TT:: . \ . . ' eas tid' By , A : yi WwW ee P4 re eueozotm ct eetss O1 034 00 2 . Final Report Illinois 1-10-62 ose, s ? seme Se inhalation eNO552 inhalation inhalation (Ly speted inhalation and 30 Above 300Vila by Above and and slightly bromenisle fare are aluseli rigure Note the dark thin The aces of the other ry25 the the sight brachial mallor spaces specially the nucleated virtually wolle ifnig bodp y apas si i pasibronchicie gigarnuteivnanpii Note EL thhiinga nhez esrsbest is this f:ielnducmle^a'terdmaisl An of the mailisofprtehseent kulene 12 a and meoo tee. Glssue se os , speted for 30 when whento 7 far3 e 03 faI re V slightly slightly h 74 1 h sos. the the - : Lett # 7303 300Vila fare fare for IV sight of of masses brachial masses sere brachiabrlachialbrachial brachial brachial Thir^ Thir^ Thir^ Thir^ magtas ars to nozens bromenisle bromenisle to dayio dayio to dayio cast by is is shemm shemm just just spaces , ni normal . az is is tasapete tasapete my arra nizom nizom nizom 4k 4k dk dk ot5 mye Cee it PECL SY in 2 x present magnification ww magnification 715. 4. High magnification higher magnifiershon magnifiershon magnifiershon of of asbestocia here ont YSBNEFe 1200 :: of the tissus coction shown in f 7. Taie par do the Garie ptseseme vis^o em 103. U rotonde gmical the fleRae~ See SS UESUD? In wis TlgAs sc rm Oo aura asbestos dust micrograph is 2 Its malls ; on: Peo inhalavis lle by inhalavis and then killed 2et 2) OATS 3g BRE33 bout: The bronchiole in this photo just above and 3 the soft of 7 nes ay vos center Tate the thickenna Gh oma 17 pure rwthisthe mail of sees 8 oe laces W we > Final Final Report Final Report Illincis 1-30-52 fh PTO. * 5 Bar's 1-30-52 En i% ry sy Oe, ke t . ig 3 bronchicles Fir, 6 lang issue of a normal guinea pig This This field shows me 3 5 longitudi- figs me ia stojo secuden at the sight of center and the the other in Longitudinel Longitudinel Longitudinel Longitudinel The other in small associated blood vessel is visible above the Longitudinel Longitudinel bronchicle in section nal section Compare the thickness of the wall of these bronchioles with the thickness of well of the bronchioles in and 7. Note also the wwoie Oo9 Be etme woe foe + emoe wm + wees seovmmee sgee .. oe temo . an oe ame sets at ems ~~ ah ... me 7. iz 7. Lung theme of a quitos ir exposed for 36 months to Kaylo dust by inhalation and Chan lies In this photomicrograph a bronchicle is just above and to the right of conter Note the thickness of the tissuz between the lumen of the bronchicle and the lumen of the adjacent alveoll in com- periton with the thin bronchiolar walls in figs 3 and 3 Note also that the greatly mickoned bronchier walls of the animal exposed to asbestos duat for 30 meath ) are similar to those of this enimal exposed to Kayic dust for 335 5 months months months Fire hands of fibrous tissus are visible near the Trenshicle Trenshicle Trenshicle in in this this photomicrograph photomicrograph photomicrograph photomicrograph photomicrograph but but but they are are more apparent because they are less denso in the area at the right of the extended to cdjacent alveciar walls 200 ) flaid thore fibrosis has hat the at at this this this Lung + Lung issue inhalation to sus ofret ofret ofret exepxpesed esed for 13 months to Tavlo sus byby inhalation inhalation ille cytoplasm packed simpleparticles duse The The The . cytoplasmDemporatess: Wrremire ' cell eee . v oa w sSe2 s2 ! 3 of the cell is simple simple with soumiati soumiati soumiati of 7 cu, cells cells in Noto rivoolur tanta tren hez hez hez sentmining numerous dust sell aaPelicante frag 01 034 0030 Fig 7. Lung tissue or a quizsa pig with infectedinfected with attozustec tubsrela bac~-ili and immediately exposed to Kzylo dust by inihalantionhalatiinhalation on for 4 killed The figuro is a slightly m^/ifiedm^/ified photograph of months the and then histologi prosdration prosdration prosdration of the routi^-a histologi lungs including back Imgs from aper o off nark foci of irregular outline in the lower center to casu The cluster median right left caudal lobs are foci of active lobe and nt the spreading distributed minute dark fest spreading tuberculosis The widelycall lymphoid te the are merely call call alustars and are unrelated te the innustica innustica innustica innustica 1%, 0 sree wm sae USI 10 10 the the filereticus filereticus filereticus filereticus filereticus filereticus filereticus wvi w wvv i ai md chew 3 pen to be axezedir ^ - maii maii 11 11 11 11 e 8 ae pen to be axezedir axezedir : ^ -maii maii . 11 11 11 Fig Fig Fig 10. Lung tissus ofof a guinea pig infected infected with attenuated and and left in closu ir ir infected tubercle bacilli for 2 months then amaemseesded for 12 maths to Kaylo cust by Inhaltreight quadrant addr addr addr addr zone irregular in outline in the loft cuphalic lobe is an area of active upper ailer but similar focus spranding spranding cuberculosis cuberculosis 4 de risible at the lower margin theft theft sephalic 1 in mail A1.g5a) inne Mg 9 the extent of the tuberculous precess is very poorly FiFigg 11. months Lung tissus infected of a guinea guinea pig empated to Regio cusctust by inhalation for months then infected infected with pig pig attenuated tubercle tubercle tubercle becillip becillip becillip becillip becillipbecillip becillip to the cust for an additional 16 months und killed . The nimisrous kierinod dark zones irregular in outline are all sites of active spreading tuberculous disease The tuberculous involve hibited in hibited this photograph issive issive issive issive noted slight in any animal killed during the experiment The involvement is relatively slight in comperisen with the progression which coeurs in animals animals to under similar exposed quartz dust dust have disd conditions in fact all of the animals exposed to quartz dust soul soul soul . within 12 months after infection because of almout compiute loss of functioning pulmonery tissuo 1,5 F 01 034 0031