Document Z4RbeeJmp4QyZ5B4zjLpk5oKJ

A Confidential Condensed Report by Donald R. Tel Iefsen. Chairman Health and Safety Ccmmittee on PERLITE DUST INVESTIGATION by The Saranac Laboratory of the Trudeau Foundation Saranac Lake, N. Y. Sponsored by Perlite Institute 10 East 40th Street New York 16, N. Y. November, 1953 COPYRIGHT 1953 BY PERLITE INSTITUTE Reproduction in whole or in part without written permission of the proprietor is strictly forbidden. Note! This is a confidential report to member companies. Please observe the copyright-- it is to protect your interest against those who may not be qualified to draw conclusions from the data or, for competitive reasons, may make improper deductions out of context. Please do not lend your copy. It should be used advisedly by your company's qualified representat Ives in contacting persons concerned with this subject. MTC 013971 June 25, 1971 <2X3 r' \ F. Coda I have written this letter at J. Siegfreid's request for the purpose of using it, if necessary, at the forthcoming New Mexico hearings. C. L. Sheckler cc: Dr. Francis Hutto P. A. Martinson E. M. Fenner J. Siegfried \ MTC 013972 THE BIOTOHCITT 0? FBRLIT1 A review ef certain animal ezperimemts end a critique of the repert from the Saranac Laboratory concerning them. SUPPLEMENT June 19, 1959 ' s/ Wfi C , AlllpLn^CC. fVt*aatttt, MD laalstant Professor of Pathology Ohio State University College ef Medicine 1*66 Meat 10th Avenue Colombo* 10, Ohio MTC 013973 The Bietexlelty ef hrlit* A review of cartel* anlnal experiment# end e critique of the report frem the Saranac Laboratory coneernlnc that* ufraoDocno* This oupploment te the review end critique submitted June 5 1959* has bee* prepared la aeeerd with the request ef Mr. Merve Merranore 1* a letter dated June 11, 1959* The supplement Is eenceraed entirely with a diocussiom ef the euggeotiona for further research projects as eutliaed In the final report frea the larsnae laboratory, titled "The Bletssleity ef fbrlite" and dated March 19, 1955* These projects were listed as fellowst A* Aether nearer in the evolutionary scale te Han are likely te react la the saae manner as do guinea pigs* A recommend a study In which Monkeys are te be used* B. Whether the progressive tuberculosis ebeerved under azperl* mental conditions Is aaeaable te satisfactory treatment by means ef nedern bie and chemotherapy. C. Whether the disabling effects of the ultimate fibrosis may be prevented or ml mini ted through the aAlrdstratlen ef eubstanees, such as cortisone, which are known te be effective against a variety of flbrotlc phenomena in Man. 1). Aether the admixture of ether eonnereial substances with Fbrlite is likely te enhance or reduce its harmful effects. I. Whether Fbrlite in a state ef finer subdivision would have effeete materially different than these ef the preduet wo etudied. MTC 013974 -2- DISCUSSION Brief e<nti concerning Mch of the propoaod projects follow. A* It li a widespread rather glib assumption that ainco monkeys and man aro both members of tho primate ordor tho reaulta of animal experiments with monkeys will bo mere closely applicable to tho hnawm situation than tho reawlta with rodenta. Thera la llttlo convincing orldonoo la ampport of thia concept, especially In tho area of tho rowponce to Inhaled dust. It la true that there baa boon a degree of apodoa variation In the reapenae of anlnala to acne aaterlala bat usually tho roaponaoa are eonalatent and In tho caao of Perlite dnat there waa no evidence of anoh apoelea variation ainco the dnat could be elaaalfied aa innoenoaa to nemal anlwala of the two apoelea guinea pigs and rata* If an experiment wfaeuld reveal that aonksyn neeponded dif ferently free tbeae two apoelea there would atill be no evidence upon which to base tho belief that monkoya would provide the bettor indication of future induatrial experience. With regard to the uae of monkaye for tho evaluation of tho effect of dnat upon tuberoulesia there la abaelutely no background experience of previoua research upon which to baae any Interpretation of experi mental reaulta* The good correlation with hunan reapenaea which haa previoualy been deaionatratod by the uae of guinea piga infected with tho apodal &}, atrain of tubercle bacilli haa no duplicate for any other apodoa* If such atndlea were to bo conducted with uonkeya it would bo necessary to conduct control experiments with quarts dnat and with other substances known not to stimulate tuberculous infection in order to MTC 013975 3- establish that aay correlation between the response of monkeys end men exists. It Is thus clear that at best several years of preliminary exploration weald be required before the experiment to evaluate the course ef tuberculous infection In monkeys exposed te Fsrlite dust could be conducted. B. This proposed experiment Is concerned with the study of the response of tuberculous infection stimulated by Fsrlite dust to treat ment with drugs, dhile it is agreed that it would bo a neat experiment there seems to bo exceedingly little indication for conducting it. It is already dear that quarts dust is considerably more potent in its stimulatory effect upon tuberculosis than is Fsrlite dust. Therefore, it seems entirely logical to conclude that since "modern bio- and chemotherapy" ia adequate to cause heeling in the presence ef tuberco lesllicesls, its effect cm tuberculous infection in the presence of Fsrlite exposure would be equally good if net even better. Furthermore sines tbs experiment has already shewn the effect ef Fsrlite upon tuber culous infection to be temporary oven without drug therapy, it seaau dear that the tendency for tuberculosis with silicosis to relapse after interruption of thorapy would not occur in tuberculous indiwiduals exposed to ftrlite. C. The nonvalidity of the assumption upon which this experlmeatd approach is based was explained in the critique submitted on Juno 5, 19$9. D. With regard to the mixture of Fsrlite with other eomaercid substances, one. can make no logieal prediction as to the readt ef exposure to such dusts. If spy such mixtures wore to bo prepared qnd MTC 013976 -U- used in substantial quantities in situations where exposure of personnel to dust night bo excessive it would seen logical that the biological activity of such Mixtures should be exaained fay means of animal experiments* S. As in paragraph D, there is no logical way in which one can predict the results of inhalation of fbrllte in a substantially different physical state fron that present in the material which has been studied experimentally* With regard to variations in particle site range, however, it is felt that only if particles of an entirely different order of else magnitude should occur would there be indication for further experimental work* Thus in the occasional instances mentioned in the report of March 19, 1955* where materials were damaging to tissue in one particle sise range bat not in another the sise differences were very substantial with the nontoxic range being measured in microns and the toxic range, in Angstrom units* lesser degrees of particle else range variation in Perlite should be of little significance* Concerning the possibility that the heating of Perlite might produce free silica crystallized in forms other than quartz it would seem that this would be of little significance unless the actual quantity of free silica were also Increased considerably above 1 percent by some means* In any case the presence of different crystal structures can be determined by x-ray diffraction studies and only if they actually occurred would there be any reason to consider further experi mental investigation in this regard. MTC 013977 SWMAHT 1. The farther reeeereh projects suggested la section 6 of the final report to the Perlite Institute froa the Saranac Laboratory, dated March 19, 1955* and titled "The BictorLcity of Perlite* have been specifically reviewed. 2. On the basis of infomation already available there seen* to be little or ns indication for pursuing the studies identified as A, B, and C. 3. Studies D and S night be required if the special industrial conditions upon which they are postulated should occur. MTC 013978 TEB EIOTCOECirr 0? OTIS ir : il >' .. V i! }v\\ Lt t. ,, U'TJ i . f . .. i . - f A reviot? of eortnin ardaal espar&aontffi and a eritiqpsa f tb rspcrt frcn th Sorsssis Laboratory ceacenairsg tbm. surnsjBHT , Jrssa 191 !?&> Assistant Prsfeasor of Pathology CM Stato Udlvorolty . Collego f Kadicina h66 Vast 10th Arona Celnabao 10, Ohio MTC 013979 Ska Bletosieity of Bbrllto .. k., . . A review of eertcin animal CCTcrinants and a crltiqaa of th report fre-n th Curasao laboratory concerning then, IGEHODCBIIOM Thio cuppler-cnt to the roricir and critique suhsitiod Jen 5, 19591 has been prepared la accord with tbs request of Mr, Karr Kairsaoro in a letter dated June 11, 1957 Km Gtipplaaeat is concerned entirely with a discussion of the orggosticcn for further research projects as outlined in the final report fran the Ccrannc laboratory, titled ^he BlotccdLcity of Pcjrlite* and dated March 15, 1955e Thus projects traro listed aa foil orat A* ITaathor caiasls nearor in the evolutionary ccala t Men aro lilasly to react ia tto era sssseae as do guinea pigs, Uc rectsscssnd, a study ia which Mostkoya are t be rsd . . Bo Whether the pre-gressivo tuberculosis ofecervod under osperi- ruatal conditions is aaeaablo 4a sstisfestory treotamt by soana f ssodcra blew* tsnd. ch&aothcrapjj* ; C, hSiother th disabling effects of tbs ultimate fibrosis say bo prevented or aialMsod through tba administration of sub stances, ouch r,3 cortisone, which aro haem to ba effective against a variety of fibrotlc phosssHscaa in Han, E, llhothor the a&aisttrro of other cewuorcial substances Tilth . Perlite is likely to enhance or reduce its haraful effects, E, Whether Bsrlito is e state of finer subdivision would have effects natorifiUy different than these of the product m studied. MTC 013980 2- ' TffSCUSSXOH Ericf cements corccraiEg each of the proposed projects folic-* i A* It ie a widespread rather glib assumption that olneo monkey and ecus are both combers of the prirnto order tho reoultc of animal c-xperiesato with monkoys will b3 moro closely applicable to tho hcaan oiteration than tho results with rodents 0 There in little convincing evidence in support of this concept, especially in the area of the response to inhaled duet* It is true that there has boon a degree of species variation in tho response of animals to eerne materials but usually the responses are eo-raiotent and in the case of Perlite dust there waa no evidence of ouch species variation aineo the dust could be classified as innocuous to rental amiaals of the two species guinea pigs and rats* If an experiment should reveal that aonfetsy rcopcstded dif ferently frsa those tiro cpocios there would still .bo no evidence upon which to base the belief that monkeys would provide the batter indication of future industrial experience* mth regard to the use of monkeys for the evaluation of tho offset of duct upon tuberoulosia there is absolutely no background experience of previous research uipcn which to baso ary interpretation of experi mental results* Tho good correlation with fcaan respuasea which has previously boon demonstrated by the use of guinsa piga infected with the special Ej_ strain of tubercle bacilli has so duplicate for any other spcciec* If such studies wore to bo conducted with conkoys it would be accessary to conduct control experinanfec with quarts dust ard with ether subataacos known not to stimulate tuberculous infection in order to MTC 013981 3- ectnbllsh that any correlation between the response of monkcya and raaa exists. It in thus clear that at boat several yearn of preliminary exploration would bo required before the experiment t evaluate the course of tuberculous infection la monkeys exposed to Porlite dust could bo conducted. B* This proposed ozpaxiEont Is concerned with the study of the response of tuberculous infection stimulated by forlit o dust to treat* mont with drugs b"iilo it is r.grood that it would bo a neat experlnont there seems to be ezeondlssly little indication for conducting it. It Is already clear that quarts dost is considerably raoro potent in its stimulatory effect upon tuberculosis than is Porlite duet* Therefore, it scons entirely logical to conclude that since Bnodern bio- and chemotherapy0 is adequate to causa healing in tha presence of tuberculosllicosio. Its effect on tuberculous infection la the presence of Bariite zpoaure would bo equally good If not oven better. Furthermore since tba experiment has already shown the effect of Porlite upon tuber culous infection to bo temporary oven without drug therapy. It seems clear that tho tendency for tuberculosis with silicosis to relapse after interruption of therapy would not occur in tuberculous indisriduala exposed to Perilto. Co The nerwalidity of the assumption upon which this experlnaatsl approach la bared was explaiised in th critique cubelttod on June $f 1?$9. D. tilth regard to the nizturo of Farlito with other carasareial substances, one can sake no logical prediction as to the result of exposure to ouch dusts* If ary such mixtures ware to bo prepared qcd WITC 013982 -li- used in substantial quantities in situations where exposure of personnel to dust night bo excessive it would seca logical that the biological activity of ouch mixtures chould .be examined by means of animal experiments. 3. La in purr.gr aph Dp there io no logical way in which one can predict the results of inhalation of Perlite in a subetantlaHy different physical state fren that proos nit in the material which has been studied experimentally, with regard to variations in particle oise range, however, It is felt that only if particles of en entirely different order of siao magnitude should occur would there bo indication for further experimental work. Thun in the occasional, instances mentioned in the report of March 19, 1955, whore Tutorials were damaging to tissue in one particle sise rang but not in another the siao differences were very substantial with the nontoxic range being measured in nicrona and the toxic range, in Angstrca units. Lesser degrees of particle also range variation in Fbrlite should be of little significance. Concerning the possibility that the heating of Perlite might produce free silica crystallised in forms other than quarts it would aocra that thin would be of little significance unlace the actual quantity of free silica were also increased considerably above 1 percent by case means* In any case tho presence of different crystal structures can bo determined by x-ray diffraction studies and only if tfc*y actually occurred would there be ary reason to consider further experi mental investigation in this regard. ' MTC 013983 5' S&SS&BT 1. The farter research projects eraggeeted la ooctlen 6 of the final report to the Parlite Institute frem. the Saranac Laboratory, dated Kerch 19, 1955# and titled ^ho Eiotozlclty of Perilto0 have boon specifically roviered, 2. On the basin of information already aTRilsbla there ocean to be little or no indication for pursuing the studios identified as A, B, and C. 3* Studios D and E night b required if the special industrial conditions upon which they or postulated should occur* MTC 013984