Document 8VD62x236r0zLnw9XGRQOx1ro

HOW TO USE THESE SEPARATORS Use one page fo r each sep aratio n . Select appropriate t a t , add fu rth e r id en tificatio n i f d e sire d , and cover it with scotch tape. Cut o f f and d isc a rd a l 1 tab s except the one covered by tap e. TABBED SEPARATOR SHEET i Fora HEM-69B i <-) < to i. !/ ) I > , ! ' A K ' M I . X 1' O F I I F A L T J 'j , H C A I O N , \ -, I > V i I i 151,10 iK A i.TH M RVfOK m o l ) AND DRU G ADORNOS 1RATION TO :Pe 1;i Lions Control Branch, H F F - 3 3 4 Attn: Dr. C . Miles d a t e : October 7, 19/4 t-ROM R e s i d u e Analysis & Methods Investigations Branch, H F F - 1 44 s u b j e c t :J o hn s -Ma n v i -.le (J-M) 9/27/74 Letter and Data on Analyses of T r e m o l ite (T) in Food. In previous data on the above subject, d i s cussed at the 9/12/74 m e e t i n g , .e inquired of J-M what did a zero f i '-er count mean in terms of ppm or ppb_ T in f o o d . Furthermore, we suggested that some fi. !te fiber count related to food content wfrtkld bo more si g ificant experimentally. J-M agreed to perform a numbe. of' spiking exferiments of meat and salt w i t h s t a n d a r d T and determine recovery data by measuring fiber count. I . Spiked Meat Based on a 100 ppb_ T spiking of m e a t , asking, mill! pore filter ing and m i c roscopic count showed 70 fibers vs a theoretical level of 98 or 72% recovery. II. Spiked Salt Based on a 1 ppb_ T spking of salt, dissolving, mill ipore filtering and m i c roscopic count showed an average (2 trials) of 3825 fibers vs a theoretical level of 4100 fibers or 94% recover y . IV. S p i k ed S alt Again, spiking of salt with a 0.1 ppb_ T level, dissolving, mi 11 ipore filtering and m i c r o s c o p i c count showed a fiber level of 290 vs theoretical 656 fibers or 45% recovery. In the following we have attempted to relate a zero fiber count sensitivity (or a m i n i m u m sens i t i v i t y count) to some detection limit of Tremolite in food based on paper wrapping of meat or packaging salt. We will have to defer this evaluation to W. Eisenberg ( M I c r o a n a 1yti :a1 Branch, HFF -12 7) who, being more familiar with the optical inicrc sco p 1c ! )u 11 in g pr o c ed u res use d f o r th e T f ib a r s , ca n p r e scribe liber count sensitivities for these analyses which will permit more accurate detection limits for the spiking experiments carried out by Johns-Hanvilie. The r e l a t ionship of the above data to J-M's original "zero f i b e r : count, if aci :ptable, presents some problems in the above spiked samples, I.a. A zero or single liber count or 100% recovery be equated to J _ x 100 ppb = 1 ppb detection limit 00 on the 98 fiber spiking. could ~ based b. l\0 70 Based or the /.>7 recovery, zero count would equate to 1 ppb. c . If a 1C fi ber r aunt were the sensi t i v i t y variation, then the detection limit would be 100 = 10 p p b . 10 " II.a. A zero o single fiber count sensitivity could be equated to __1 ___ = 0.25 ppt detection limit based on the 4"; 0 0 4000 fiber spiking. ' b . A 100 fib - count sensitivity would provide a detection limit of 10 ppt. IV.a. A zero fiber count sensitivity could be equated to 0 . 1_ = 0.3 p p t . To b . A 100 fiber count sensitivity would provide a detection 1 imi t o f 0.9 pp;t. 'TA* ') Vv< // A. Holtz zsr , A -if 'f A A * ' ^ ' Aj/ (A /If u<;.v-'- 'C'S'i* .TA A kA a A*? . .V // (A`1 * / *v J-jhi.s-ManvHie Research & Development Center D enver, Colorado 8021 7 (303) 770-1000 Sept omher 2 7, i974 o Dr. Corbin Mi let, (HFF-335) Food & Drug Adminis tration 200 C Street, S.W. Washington, D.C. 20234 Dear Corbin: At our last meeting with you on September 3 2, 1974 , you raised a question reyardin'" the limits of detectability o : tremolite in various fo. d "ant,pies . The main reason for your question was to bo a .=le to specify a reasonable lower limit to 0 fiber counts. In order to answer your question, we agreed to perform the following three tests: 1. Determine the limit of detectability of tremolite in salt spiked with tremolitic talc. 2. Determine the limit of detectability of tremolite in moat spaced with tremolitic talc. 3. Determine the'limit of detectability of tremolite in salt spiked with ash from paper manufactured with tre" molitic talc. The details of the experiments are attached. All of the counting was done by the optical microscope at 500X magni fication. The samples were prepared by filtering on a 47 mm diameter, 0.2 micrometer millipore filter. The maxi mum amount of total material which can be deposited on this filter is 0.5 mg. Any gieater concentrations result in too great a probab i.l.ity of fibers being hidden behind other particles. The results that we have obtained indicate that tremolite can be detected at a level of about 20 ppm in any residue. The detectabiliby in any foodstuff will, therefore, depend upon the amount of ash remaining when the food is ignited. -trap; -;/r"aa/' & / o, C o rb in j s i l o s , FDA \,t u ;l i in g t o n , D . C . Soptember 27, 1.774 Page 2 As an example, if a food yields 1 per cent ash, then the limit of detectabili ty of: 'r< molite in the food ; ould be 200 parts por billion. In the a se of the spiked salt, the limit of detectability is abo1t 0,1 parts per billion. be hope -that this information has answered your* questions. f we can be-of any further assistance, pleace do not hesitate 7.0 contact either Rich t izenski or myself. As yr requested, uneb.separate cover we are also sending sevej ..1 paper samples made with ' .rious amounts o ? tremolitic talc. Very truly yours, Dr. ..lames P Leineweber Manager, Rg ied Research Rid *;d J. Z.-xenski P.oso ;ch Fng near is Attachment Attachment Dr. Corbin Milos , FDA LIPPLEMBNTA nY F m WORK Item 1 : 150 got oi meat was spiked with 0,0060 gm of F~1 talc standard (0,25 pe_ co c tremolite). This produced the equivalent of 100 ppb trem, .neat, Based on the original fiber count of 41,000 tremolit'c fihers/ng of F-l standard, there were approximately 246,000 libers contained in the ash. The 150 n : of meat ashed down to 1,25 gm. For i xerographic slide prep -ation, 0,5 mg of this < bed was dispersed on a 47 mm rail1'.pore fi. ter. Assuming a homogeneous mix of ash and'fibers , the ,,,e should have been approximately 9 8 tr<. lolite fibers depo sited on the millii are filter. Optical examination observed 70, Item II: 250 gm or salt was spiked with 0.1 mg of F-l standard. In the 0.1 mg of talc, there were approximately 4 ,100 fibers. . This corresponds to 1' ppb itremolitc/salt. .The salt was com-, pletely dissolved and filtered through a 0.2 /J millipore filter.. Tf no fibers we. e lost during the.procedurep all of the 4,100 . Libers should have been collected on the filter. Optical exa mine ion observed 4,200 tremolite fibers on one sample and 3,450 fibers on arm ther. ' T 'ern III : A paper containing 3 per cent CYCLO-FIL talc was c ied and prepared for tremolite fiber count. The count was 350,770 30 per cent tremolite fibers per mg/ash. Then 0.1 mg of th s paper iah was mixed with 250 gm of salt and the procedure for the recovery of ins, lubles was performed- - If no fibers were lost during preparation, there should have been approx ainately 39 ,000 fibers collected on the filter. Optical examination revealed 35,000. - Item IV: 400 gm of salt was spiked with 16 micrograms of F-l s tandard. This introduced approximately 656 tremolite fibers into the salt. 'dais corresponds to approximately 0.1 `ppb !.:<om./salt. Tina salt was dissolved and filtered through 0.2 miilipore. Optical examination observed 290 fibers. R. J. 5aronnki 9 -2774 Between: '0 MEMORANDUM OF CONFERENCE * ' ^ September 12 1574 Gorbin I. Miles, GRAS Review Branch, DFCA/HFF William V. Eisenberg, Microanalytical Branch, DM/HFF Albert. Holtz, Organic and Additives Branch, DCP/HFF and Richard Carter, Johns-Manville Richard Lamar, Johns-Manville Jim Leineweber, " " Richard Zazenski, " " . . ` * Subject: Response to FDA Questions on Migration Data Discussed on February 27 1974. * Mr. Carter requested this meeting to explain the details of J-M's response to questions raised by FDA personnel on February 27, 1974. J-M's written response to these questions, dated September 4, 1974, was received by FDA personnel on September 9, 1974 and represented the total substance of this meeting. The above FDA personnel were generally satisfied with J-M's response to questions, as presented in the September 4, 1974 memorandum. Hr. Eisenberg suggested, however, that the following further studied be conducted by J-M, to demonstrate the lowest limits of detection for tremolitic talc in various food samples. The suggested studies were as follows: h 1. Determine the limit of detectability and recovery of tjfemollte in salt (as a representative of other dry packaged foods) by spiking a sample of salt with a small measured amount of standardized ale. 2. Determine the same limit of detectability and recovery for a meat sample, in the same manner as above. 3. Repeat the above test (1) with tremolite from ashed paper made with tremolitic talc. The intent of this study was to distinguish any difference between standard tremolitic talc and tremolitic talc after ashing. OOtTisf op mmnn-ni piiPtn Pri Pmi All persons at this meeting agreed that these studies were necessary to jvcharacterize the limits of detectability expressed in previous J-M data. J^Dr. Miles also expressed the urgency required for completion of these ^studies, so that these findings could be incorporated into a presently drafted FDA regulation on this matter. Mr. Carter thought that this !..r^XJJnadditional work could be reported within three weeks. ;1TCS~O0i oa oft ---------------------------------- ------- Corbin 1. Miles, Ph.D., KFF-335 Johiis-Manville Coi\. ,,ration Greenwood Plaza Denver, Colorado 30217 Environmental Affairs Department 0 September 4, 1974 Dr. Corbin I. Miles GRAS Review Branch Division of Food and Color Additives Bureau of Foods Food and Drug Administration 200 C Street, S.W. Washington, D. C. 20204 Dear Corbin; As you will recall, on December 21, 1973, Johns-Manville Products Corporation submitted written comments to the Food and Drug Administration in response to FDA's Notice of Proposed Rulemaking relating to asbestos particles in food and drugs, as published in the Federal Register Q AmV. 1*^-v OQ *1 *7 4 4 rr-p. ^ -P^ ^ 4-^ 4 -^ riupu&cij. } . On February 27, 1974,- Dick Lamar and Jim Leineweber of our Research and Development Center and myself met with you, A1 Holtz and Bill Eisenberg to review eleven questions raised by FDA with respect to our December 21, 1973 submission. On April 2, 1974 , I forv/arded a letter to you outlining our understanding of the eleven questions posed, setting forth answers to those questions where information was readily available and outlining what we proposed to do to provide the requested information for the remaining questions. Attached to this "letter, is a memorandum listing each question posed and the information requested by FDA and Johns-Manville`s responses thereto. Included in this memorandum, for the purpose of clarity and continuity, are those questions previously answered in part or in full in my April 2, 1974 letter. ' The necessary research work undertaken to provide FDA with the information requested has taken a considerable amount of time. This was due to the nature of the work involved Dr. Corbin I. Miles Page 2 September 4, 1974 and the considerable demands placed on our Research facilities aid personnel with respect to other important projects. Additionally, our Research personnel place considerable importance on the integrity of the research work undertaken in response to FDA's questions and the necessity to obtain valid results. The results of the research work undertaken in response to FDA's questions confirm the conclusion reached by Johns-Manville in our submission dated December 21, 1973, that tremolite does not migrate from paper packaging materials containing tremolitic talc to the food or drug contents during commercial handling and shipping. It is our hope that FDA will reach the same conclusion from the attached memorandum, and as a result, will not impose any restriction on v'e v.f c. of talc containing tremolite in -poi''d and drug packaging applications. J..1L ut:iCJ^'UUUC vcioatiun yCOLClUay f I am not enclosing the original photographs or charts, as we do not have any additional copies. I will bring the originals with me for our meeting at 2:30 P.M. on September J 2. Did; Lamar, Jim Leineweber and Rich Zazenski from our Re march and Development Center will accompany me at this meeting. I look forward to seeing you on September 12 and hope it will be a most productive meeting for all concerned. We will be prepared to answer questions which you and your associates may have with respect to the attached memorandum. Very truly yours, Richard P. Carter, Director Government Relations RPC/emr Attach. MEMORANDUM PREPARED BY JOHNS-MANVILLE PRODUCTS CORPORATION IN RESPONSE TO ELEVEN QUESTIONS POSED BY THE FOOD AND DRUG ADMINISTRATION AT A MEETING HELD ON FEB. 27, 1974 These questions and the answers thereto relate to the comments dated December 21, 1973, submitted by Johns-Manville Products Corporation to :he Food and Drug Administration in response to FDA's Notice of Proposed Rulemaking relating to asbestos particles in food and drugs, as published in the Federal Register on September 28, 1973. The questions raised by FDA and Johns-Manville's responses thereto are as follows: QUESTION 1 WHAT IS THE RELATIONSHIP BETWEEN THE FIBER COUNT AND THE SURFACE AREA OF THE CONTAINER (FOOD CONTACT AREA)? The areas for the various food containers are as follows: Salt shaking or scuffing test Macaroni container Carnation dried milk O m r>k- ri rp Cornflakes Morton's salt -18.18 sq. in. 88.0 sq. in. 138.0 sq. in. u n n err iTt 304.0 sq. in. . 45.0 sq. in. In the case of the five packaged food items, TEM and petrographic analyses could not detect the presence of tremolite in any of the food that was packaged in tremolitic talc containing paper. Thus, the ratio of fibers to food contact area is zero for each item. There was no migration. In the case of the four test containers (salt packaged in tremolitic-talc containing paper) that were shipped by truck approximately 4,000 miles, petrographic analysis revealed no evidence of the presence of any chrysotile or tremolite fibers due to migration. TEM examination of all four samples indicated only the possibility of one tremolite fiber in one of the test contents. For all practical purposes, the ratio of fibers to surface area for each of these samples is 0 fibers/18.18 sq. in. (Each container had an effective contact area of 18.18 sq. in. and a void space of 15 percent interior container volume to allow free movement of contents within the container.) QUESTION 2 WHAT ARE THE LOWER LIMITS OF DETECTABILITY BY TEM, PETROGRAPHIC AND XRD METHODS FOR TREMOLITE AND CHRYSOTILE IN TALC? The work which was undertaken to respond to this question should be qualified in one important aspect. We have interpreted the limits of identification to mean the levels at which positive identification can be made by each method. As a review of the data below will indicated, this is an important consideration. A. Petrographic identification of tremolite and chrysotile in comminuted talc using Johns-Manville1s modified FDA method at a magnification of 500X. 1. Tremolite - In general, positive identification of tremolite can be made on fibers as small as 2.5 x 7.5 microns. However, in some samples examined, positive identification can be made on fibers as small as 1.5 x 5 microns. Unlike "fibrous talc", the Becke line can be followed readily if there is a mis-match in indices of refraction. However, by our method, we use an index oil of 1.622 to match the gamma index at the position of inclined extinction which can vary from 14 to 20 degrees (gamma index relative to the Z direction). Tremolite is also non-pleochroic whereas actinolite and ferroactinolite can be highly pleochroic, accompanied by higher indices of refraction. An experienced petrographer will also look for good cleavage along (110) , parting along (100), and twinning along (100), and sometimes along (001). At a position of 90 degrees from inclined extinction, the fiber will show high relief since alpha index is indicated and is on the order of 1.599. 2. Chrysotile - The identification of chrysotile is very much like tremolite since positive optical identification can be made on fibers as small as 2.5 x 7.5 microns. s The technique involves using 1.566 oil to capture the gamma index in parallel extinction in which the fiber will disappear or show Christiansen effect in plane polarizid light. At 90 degrees from the gamma position, the fiber will show high relief since the alpha index is 1.549 or less. Maximum interference color (Birefringence) is shown at 45 degrees. It is not unusual for chrysotile to show undulatory extinction. Fibrous talc also shows parallel extinction, but the relief is high in either direction; but a match with the 1.556 oil can occur anywhere from 45 to 80 degrees. B. TEM detectability 1. Tremolite - Tremolite fibers cannot be positively identified by TEM. Usually, tremolite is verified by chemical, optical or X-ray diffraction methods and then dense asbestiform amphibole morphology is viewed by TEM as tremolite. The eleftron diffraction pattern of tremolite is similar to all other mono-clinic amphiboles. (See Figure No. 1, attached). Using the RCA EMU 3B, it is possible to see tremolite on the order of a few hundred Angstrom units. However, it appears to be the nature of tremolite to remain on the coarse side when compared to chrysotile. -3- 2. Chrysotile ~ Chrysotile fibers can be positively identified by morphology and electron diffraction. (See Figure No. 2, attached). The electron diffraction pattern is distinctive since alternate rows of ' Laue spots are not spots but rather elongated streaks. The morphology is most unusual since chrysotile is characterized by an internal low density tubular structure which is sometimes beaded. The most narrow of individual fibrils of chrysotile are on the order of 250 Angstrom units. Below this width, the mineral ceases to be chrysotile. The most common magnification employed for the study of chrysotile and asbestiform amphiboles is 8000X. The negative is enlarged 2.5 times to provide an 8.5 x 10-in. print at a magnification of 20,000X. C. XRD identification Qualitative evaluations at 2/minute and quantitative evaluations at i/4/minute were performed using Ni filtered CuK radiation. 1. Tremolite ~ Witn qualitative examination through the 9.4 A peak area., detection could be made at the level of 0.5% tremolite in talc. However, quantitative ov;' i.udtiuii ecu.?:" -c~ ae maae oexow .u% even tnnunn samples correa;..i'i 0.0, 0.25, and 0.5% tremolite were compared to back-ground counts, with none having counts above background. % 2* Chrysctile - While 1.0% chrysotile can be detected by XRD under the 7.3 A peak, positive identification by this maans may be difficult because of the conflict between major chlorite peaks and serpentine peaks. The former appear at 7.3 and 3.65 A and would obscure chrysotile concentrations. Serpentine has a minor peak at 2.15 A which differs slightly from the minor 2.10 A peak, but neither would be apparent at low concentrations of either mineral or combinations of the two. In the absence of chlorite, 1% chrysotile (in talc) was measurable, but small quantities of chrysotile in the presence of serpentine would not be detected. From the foregoing, we believe the following conclusions can be substantiated:1 (1) Individual tremolite particles 2.5 x 7.5 microns can be positively identified petrographically and under some circumstances, particles as small as 1.5 x 5 microns can also be identified. -4- 0 (2) Tremolite particles cannot be positively identified as such by TEM, since they cannot be distinguished positively from other amphibole minerals. (3) Tremolite particles can be detected at the 0.5% level by XRD but their quantity cannot be determined accurately below i.0%. (4) Chrysotile fibers 2.5 x 7.5 microns can also be positively identified petrographically. (5) Chrysotile can be positively identified by TEM morphology and electron diffraction, with the lower limit of fibril width being of the order cf 250 Angstrom units. Below this figure, the mineral ceases to be chrysotile. (6) The chrysotile content of talc can be determined at the 1.0% level only if the commonly associated minerals, chlorite and serpentine,are not also present. If they are present, chrysotile may not be positively identified. QUESTION 3 i ' K U V r D E V A b i L ' A ' i ' J . UJN A N D K K f t i V K K Y D A T A K D H T K K M O U T K A N D f ' H R V q n ' P T T . F IN SPIKED SAMPLES OF TALC - SAMPLES OF TREMOLITE AND CHRYSOTILEFREE TALC TO WHICH KNOWN AMOUNTS OF TREMOLITE AND CHRYSOTILE HAVE BEEN ADDED. % The following data contains our findings with respect to Petrographic, TEM and XRD examination of a series of standards made from amphibole free talc and varying percentages of tremolite. In addition, XRD examination of similar talc - chrysotile standards was made, but a set of talc - chrysotile standards suitable for Petrographic and TEM examination was not available. Because little, if any, chrysotile-containing talc is used by the pulp and paper industry, it was decided that the very time consuming preparation of such standards was not warranted in view of the detection data already made available. A. Tremolite validation The following tabulation sets forth tremolite content vs. numbers of "fibers" in talc samples. In all cases, the number of tremolite particles should be read as 20%. So-called fibers are tremolite particles having a 3:1 aspect ratio and a length of at least 5 microns counted at 500X. Sample Percent Tremolite By Weight No. of Tremolite "Fibers" per mg of Talc F--1 Standard 0.25% 41.000 F-2 Standard 0.50% 61.000 F-3 Standard 1.00% 111,000 F-4 Standard 2.00% 207.000 F-5 Standard 4.00% 400.000 F-6 Standard 16.00% 1,800 ,000 Tremolite-free Talc 0 The slight lack of linearity is due to the difficulty in obtaining sufficiently dispersed slides to permit unhindered counting, i.e., a top layer of particles obscuring lower layers, and the counting precision noted above. Fiaures 3 and 4. attached, are elprtrnn nhnfnmi rrmranhs fTtavn -P 4-rt^ ^ -C J_'U _1____ __ __ 1--1 -v .1 . '*'** ~ --~ - -- -- 1 is-* *- _ s. 5- X. ' j s-'.J- v-- -i- * - 1 Ji.v_ U.X. ^ JlltV-/ -1_ JL -- J.JLCC talc at 20,000X as reproduced here. Figure 4 is the same talc spiked with 0.5% tremolite (F-2 Standard). There are three (3) tremolite "fibers" present and these are the most dense in the 'entire print. Other similar looking particles in both pictures are talc platelets on edge. Each tremolite particle identified represents 1,1)0 particles per mg of sample. Figure 5, attached, is a composite XRD tracing covering the same series of samples used for the petrographic examination. The various levels of tremolite added,from 0 to 16% by weight, are indicated along with the height of the 9.4 A peak for each. For samples having no or 0.25% tremolite, there is no discernible peak. At 0.5%, an identifiable peak appears which becomes more prominent as the percentage of tremolite increases. This latter phenomenon can be used to estimate the amount of tremolite present when compared to a sample containing a known and discernible amount of tremolite. This is done by determining the number of counts or units of area under the peak. Figure 6, attached, is a plot of counts vs. tremolite content of the same standards, extended in this case to include one having 50% tremolite. All counts are corrected for background. The lowest level having a count above background is 1.0%. Above this point, the relationship between point count and tremolite content is seen to be quite linear, and it could be used as a reliable means of assessing tremolite content above that level. B . Chrysotile As noted previously, no comparable series of chrysotilespiked samples suitable for petrographic and TEM examination is available. Differences in the manner of dispersion of the fibers,makes samples for microscopy much more difficult to prepare than those for XRD. Some samples for XRD were prepared for this study. Figure 7, attached, is a composite XRD tracing of talc, and talc with chrysotile added in the amounts of 1.2 and 2.2% respectively. It should be noted that the 7.3 A peak is sufficiently well developed to indicate that a quantitative evaluation could be made at about 1%. However, It must be emphasized that chlorite and serpentine produce identical to similar peaks if present. As an illustration, Figure 8, attached, is an XRD tracing for a mixture of 60% chrysotile and 40% serpentine (without talc) showing the peaks between 2.10 and 4.57 A. Only the peaks at 2.10 A for chrysotile and 2.15 A for serpentine are distinguishable. However, if these were included in a mixture which was mainly talc, they would no longer be discernible. a h '- cujw v>- x l - u u o u i i c p u n t - j. u o - L p n t : 1 t. y >r /, x v . - t a j i positively and quantitatively identified by petrographic or TEM means. However, a quantitative'gravimetric evaluation must take into account that chlorine and/or serpentine minerals cannot be present. QUESTION 4 A REQUEST WAS MADE THAT, WHEREVER POSSIBLE, WE RETAIN ALL SAMPLES, PREPARATIONS, SLIDES, ETC. Wherever possible, we are doing this. Petrographic slides, however, are not permanent. Immersion oils change with age and exposure to air. We are retaining the negatives for all TEM's. QUESTION 5 IN OUR SALT-SCUFFING TESTS, DO WE HAVE DATA FOR 10 CPS TESTS SIMILAR TO 19 CPS TESTS? DO WE HAVE TEM TEST RESULTS AT 10 CPS? DO WE HAVE RETAINED ASH SAMPLES? The data on the 10 cps test is as follows: -7- Sample RS 73242-2A RS 73242-2B Residue Due % Talc To Scuffed in Paper Paper (gms) 1.0 0.00000 1.0 0.00000 Number of Talc Particles* 0 0 Number Of Chrysotile & Tremolite Fibers 0 0 *Residue viewed petrographically at 500X These results are discussed on pages 3 and 4 of Report No. E414-2, Preliminary Studies of Food Contamination by Contact with Paper (Exhibit ~T~, Jobins-ManviTXe suBmissioh dated December "ITJ 1973). There are no TEM results at 10 cps, as there are none for any of the artificial test results. TEM analysis began on samples that had actually endured road travel and on the analysis of actual food contents. Except for TEM negatives, we have not retained ash samples of any work prior to March 1, 1974. Whenever possible, we are doing so now. Although FDA requested that we repeat these salt-scuffing tests, based on the research work undertaken in preparation of our submission dated December 21, 1973, and based on the additional work reported herein, we have reached the conclusion that it is futile to run additional artificial scuff tests at this time. An artificial test is generally any test which simulates an uv.Lual ui.ouj.iciu,u. il is usuaiiv run on a smsi ipt r ps ip anri at accelerated times. Before any laboratory test can be designed to simulate an actual or large-scale occurrence, all of the parameters and variables must be known so that they can be scaled down correctly. Only by knowing these parameters and variables, can one even begin to design and build a simulated model which will produce valid test results. In the case of the artificial scuff tests, we were requested by FDA to run and re-run paper samples on the artificial scuff tests. It was assumed that a test of this nature would simulate the vibrating action which food packages undergo during normal commercial shipping and handling. This is a dangerous assumption. The simple procedure of placing a test container on a vibrating table, vibrating at an arbitrarily chosen amplitude and frequency for an arbi trarily chosen period of time , simply cannot be said to simulate actual shipping and handling. Any conclusions or correlations between this artificial test and actual road travel would be completely unfounded. Yet, in the months of study on this subject, many people have tried to compare the two. Such erroneous assumptions can lead to mistaken conclusions. Based on the research work completed thus far, we: have concluded that the only data which warrants consideration is that data which is supplied by examining actual food contents and test contents that undergo actual road travel. For these reasons, -- S- the results and conclusions discussed in Report No. E414-6, Lack Of Food Contamination By Contact kith Paper Due Tp Shipping (Exhibit II, Johns-Manville submission dated December 21, 1973), and the data furnished in response to Question 9 herein, should be regarded with the utmost importance. QUESTION 6 PROVIDE A DESCRIPTION OF OUR METHOD AND A SAMPLE CALCULATION OF OUR XRD ANALYSIS OF FOOD PACKAGING PAPER FOR TALC CONTENT. XRD analysis of food packaging paper for talc content is performed by scanning the paper over the 9.4 A peak and computing the percent of talc present from the ratio of the area count obtained for the unknown paper to the area under the peak of a standard paper of known talc content. Papers of verified talc contents ranging from 0.53% to 12% talc are used for standards. A. Sample Calculation: Unknown Paper Sample Scan 200 sec from 9.9 to 8.23 20 = 64,056 counts RanVrfrnnn^ no-f-A rm i yr)p Count for 100 seconds at 9.9 20 = 25,394 counts Count for 100 seconds at 8.23 20 = 24,187 counts 49,581 counts (total background count) 64,056 counts (total sample counts) -49,581 counts (total background courts) 14,475 counts .contributed by talc m paper sample B. Standard Sample: 2.5 Percent Talc The same procedure determines that the 2.5 percent standard has a total count due to the talc of 15,069 counts. The percent talc in the unknown paper sample is computed by: 14,4 75 counts (unknown sample)______ , _ _ 15,069 counts (2.5 percent standard) X ' a c ~ 2.4% talc in unknown paper sample QUESTION 7 IN TABLE IV-A ON PAGE 11, REPORT NO. E414-2 (Exhibit I, JOHNSMANVILLE SUBMISSION DATED DECEMBER 21, 1973), THE SIX-HOUR RESULTS APPEAR OUT OF LINE. CAN THIS ANOMALY BE EXPLAINED? -9- As for the irregularity of the six-hour results, we can only suggest the possible source of error, since a definite explanation is not known. We strongly believe the anomaly is a result of a human error, probably committed early in the weighing procedure. The belief that the anomaly is due to human error, is strongly supported by the other data. Since six out of seven data points form i definite, regular curve, and since the irregular data point is not at either end of the curve, but somewhere in between, scientific logic suggests that the point should be disregarded and labeled as a procedural error. QUESTION 8 PROVIDE VALIDATION OF THE MEAT WRAPPING AND SAMPLING TESTS AND THE SENSITIVITY OF THESE TESTS. IN ADDITION, RELATE ANY MIGRATION TO MEAT SURFACE OR MEAT WEIGHT. This question relates to the McCrone meat wrapping studies (Exhibit E, Johns-Manville submission dated April 20, 1973) in which talc-containing papers were placed in contact with raw meat. Subsequent examination of the meat, both in thin sections and after ashing, showed no migration of -cremolite. jm e q u e t ,L .x o n i d i s e u o y r u t\ w a s w i i e t n e i c a r s c o ;_ n.' ikj tremolite would have been detected if present in the meat in McCrone1s studies. The answer is essential to the validity of McCrone's finding that no m: graticn of -cremolite had occurred. An experimental plan, a copy of which is attached hereto as Figure 9, was devised to confirm the presence or absence of tremolitic talc on meat under known conditions. Preliminary experiments indicated that there is no practical way to determine the lowest level of detectability, which was one element of the FDA question, because we could not uniformly spread extremely small amounts of tremolitic talc over a known area. Applications of the order of 0.1 to 0.2 ing/cm^ are so apparent, however, that the limit of detectability is probably at least three orders of magnitude lower, i.e., 0.0001 to 0,0002 mg/cm^. We were unable to devise a means of applying such small amounts. Test Results Using the procedure described in Figure 9, samples were prepared from three steaks, the first a control having no contact with tremolitic talc except what might have come from the wrappings and mask, the second having an applied dose of 0.12 mg/cm^ of J-M CYCLO-SORB, and the third having an applied dose of 0.16 mg/cm^ of J-M CYCLO-FIL. Samples of all paper in -10- 0 contact with the meat were also obtained to identify any source that could have lead to contamination of the control. The three samples of raw meat scrapings were examined by optical microscope at 500X. Results are reported as follows: Sample Number Sample Talc Tremolite 4384-38-4 Meat Control (Fig. 10) None detected None detected 4384-38-5 Meat with 0.12 mg/cnm (Fig. 10) CYCLO-SORB Present Present 4384-38-6 Meat with 0,16 mg/cm^ (Fig. 11) CYCLO-FIL Present Present Three pictures, attached, as Figures 10 and 11, are photomicrographs of the three meat samples above, taken at 500X. It should be noted that talc and tremolite particles are readily visible in the samples to which CYCLO-SORB and CYCLO-FIL were applied, but neither talc nor tremolite could be confirmed in the blank. r y P T . O - F T T.--r i n c c ^ r n r 'l <=> c o i l l -f-Vip T ifo V > l orn +~i n n o H w .1. -t. J. A- V-/J- UUiUiliy WCU UJ.O -L ^ ___ L V U \ J - VCL V small amounts of talc, in this case 0,16 mg/cm , and obtaining representative samples therefrom. The fibrous material in all of these pictures is part of the raw moat structure. Meat and paper samples were then ashed for 16 hours at 800F. There was considerable difficulty in reducing the carbonaceous content of these samples to low enough levels to permit reliable examination, but this was finally achieved. Optical microscopy results are as follows: Sample Number Sample Talc Tremolite 4384-38-4 Meat Control None detected None detected 4384-38-5 Meat w/CYCLO-SORB Present Present 4384-38-6 Meat w/CYCLO-FIL Present Present 4384-38-1 Mask Paper Trace None detected 4384-38-2 Outside Wrapper Trace None detected 4384-38-3 Meat Contact Wrap None detected None detected The final part of FDA's question relates to number of tremolite particles applied meeting the standard of 5/-f length with a 3:1 aspect ratio. The 0.12 mg/cm2 CYCLO-SORB applied is estimated to contain 390,000 (20 percent) tremolite particles meeting the above criteria. The 0.16 mg/cm2 CYCLO-FIL applied is estimated to contain 1,250,000 (20 percent) tremolite particles meeting the criteria. No attempt was made to enumerate talc particles in either case, since such particles do not generally fit the criteria. However, many millions of particles can be seen and particle size analysis indicates that theie are many millions more that are sub-optical microscopic. Based on the high numbers and degree of detectability of both talc and tremolite particles on meat samples and ash in this study, it is concluded that McCrone's finding, that migration of tremolite from the tremolitic talc-containing wrappings did not take place, is valid. Had even a very low order of migration taken place, it would have been detectable. QUESTION 9 PERFORM BOTH SCUFFING AND SHIPPING TESTS USING PAPER WITH HIGH LOADINGS OF TREMOLITIC TALC (PAPER WITH THE HIGHEST LEVEL OF T P E H n r .T T T r 1 T S T .r m u a m t ? o n M M V D O T b t .t .v rT Q P n p o p p n n n c a n r a n n i r . w u a m See our answer to Question 5 as to why we did not perform additional scuffing tests. As requested by FDA, salt shipping tests were repeated, employing papers with high loadings of tremolitic talc. To briefly review the test , it consists of lining salt-filled glass jars with test papers and shipping them by truck approximately 4,000 miles (For a more complete description of the test procedure utilized, see Johns-Manville's submission dated December 21, 1973). By utilizing this procedure, we can duplicate, if not exceed in stringency, the conditions under which food packages are shipped. The test results reported hereinafter were obtained from papers with exceptionally high loadings of tremolitic talc. The papers used to line the salt-filled glass jars contained 9%, 14% and 20% of Johns-Manville's CYCLO-FIL talc. The 9% and 14% CYCLO-FIL papers were obtained from a Johns-Manville customer which purchases CYCLO-FIL. The 20% CYCLO-FIL papers were previously made by Johns-Manville for testing purposes, using CYCLO-FIL. Therefore, we knew that tremolite was present in all of the paper used to line the salt-filled glass jars, as CYCLO-FIL contains approximately 30% tremolite. To confirm the presence of talc in the paper used in this test, the analytical method -12 set forth in our answer to Question 6 of this memorandum was utilized. Our XRD analysis of these papers confirmed the presence of talc. It is essential to note that after an exhaustive search, we were unable to locate any food packaging paper containing loadings of talc in excess of the paper utilized in the salt_shipping tests reported in Exhibit n to our December 21, 1973 submission. As noted in our December 21, 1973 submission, papers with high talc loadings would normally not be used for direct food packaging applications. However, FDA requested that we specifically subject highly loaded talc papers to the salt shipping test. Therefore, these highly loaded talc papers, which are manufactured for such purposes as writing paper, textbooks, etc. (as indicated by our customers), were utilized. A misunderstanding which may have arisen from our December 21, 1973 submission should be clarified. High brightness talc (i.e,,, CYCLO-FIL) is used in the manufacture of fine paper products as a high-brightness filler and opacifying pigment. Its loading ranges may vary from 2% to 15% by weight. CYCLO-FIL and other related ultra-fine particle size white pigments are used to increase opacity and brightness and in many instances t-o imnrnyp fhp nrintirm nnararr.pri sties or rne DaDer. Ine rO tra-fine particle size also develops a unique synergistic effect when blended with Ti02 . It not only acts as a spacing mechanism, but also attracts the Ti02 to the platey planar " surface, thus resulting in increased efficiency from TiO? Jt fSciCjCi However, it is important to emphasize that high brightness fillers and pigments are used only for fine paper products, such as printing (magazine) paper, writing paper, labels, etc. Cos'cs prohibit its use in paper whose application does not warrant high brightness and opacity, such as newspaper, cardboard, paper bags, etc. Most paper which is used in food packaging applications would fall into this second loxver grade category. There is no need to load this paper that comes into direct contact with food with high brightness fillers and pigments, because it is rare that this paper is ever used for outside labeling. However, this lower grade paper (lower grade so far as brightness and ink receptivity are concerned) is generally then wrapped with a bright, high grade paper, which is then suitable for labeling and attractiveness. Therefore, papers that are loaded with high concentrations of high brightness pigments and fillers are used only indirectly so far as food wrapping applications are concerned. This type of paper is normally not used in a direct food-contact basis. As a result 13- of all of our research efforts and investigations, we have been unable to locate food packaging paper containing more than 1.5% talc. Such paper was utilized in the scuffing and salt shipping tests reported in Exhibits I and II of our December 21, 1973 submission. The salt shipping tests which were repeated with highly loaded talc paper, utilized the identical test procedure employed in the tests described in our December 21, 1973 submission. The results reported in Table 1 below were obtained by employing the TEM at 11,000X. The proposed FDA criteria for identifying asbestos fibers (as published in the Federal Register on September 28, 1973) was employed. i Table" 1 Examination of Shipped Test Sample Residues By Transmission Electron Microscopy - Plain Uncoated Paper Sample No. Percent Talc in Paper 11,000X TEM Plate No. Chrysotile Tremo1 4385-78-7 9 2282A B C D E 0 0 0 1 Bundle * xu --- xOIivj 1 Fiber * 10 long 0 0 0 0 U 4385-78-10 14 22 83A B C D E 00 00 00 00 00 4385-78-12 20 2284A B C D E 00 00 00 00 00 Table 2, following, reports shipping test results using the same papers, after they were coated with a thin film of Flexbond 811 prior to testing. As indicated in our April 20 and December 21, 1973 submissions, paper food containers are normally either lined on the inside with plastic (such as polyethylene) or coated with a thin film of wax or plastic. This is done for two reasons: (1) to help keep the food fresh, and (2) to prevent the paper from absorbing moisture, oils, taste and fragrance from the foodBecause this is a real situation, we decided to simulate this type of container to see if it was possible for the salt to abraid through the coating, thus exposing the paper to the food. The Flexbond 811 employed in this test was a polyvinyl acetate co-polymer. *Most likely due to contamination, as bundles of chrysotile are not found in Johns-Manville's -14- Table 2 Examination of Shipped Test Sample Residues by TEM Papers Coated with Flexbond 811 Sample No. Percent Talc in Paper 8,000X TEM Plate No. Chrysotile Trem Salt Blank 229 3A ' B C 00 00 00 4385-78-7F 9 2290A B C 00 00 00 4385--73-10F 14 2291A B C 00 O' 0 00 1735-7 B--12F 20 2292A B r 00 00 00 CONCLUSIONS: 1. The results reported in Tables.1 and 2 clearly indicate that even the most severe of actual shipping and handling conditions are not severe enough to cause distruction of food packaging paper. Since the paper is not degraded, there is no migration of tremolite fibers. 2. The above conclusion is supported by shipping test results on test papers that had as little as 0.25% tremolitic talc to as much as 20% tremolitic talc. 3. The results also indicate that the migration of paper additives, such as tremolitic talc, depends on the strength of the paper and not the amount of additives that are contained in the paper. Since we have determined that the paper itself must be physically degraded in order for migration to occur, and since we have found that actual shipping and handling conditions are not severe enough to cause commercial paper to degrade, the fact remains that regardless of the quantity of tremolitic talc which commercial food packaging paper may contain, there should be no fear of tremolite migration and contamination. The conditions are simply not present to cause such an occurrence. To visibly demonstrate this conclusion, we have attached SEM photographs displaying the surface of one of the test papers (14% talc by weight). Figure 12 -- 15- 0 attached, is a picture of the surface of the paper before going through the shipping test. Figure 13, attached, is a picture of the surface of the paper after testing. Both pictures are virtually identical and indicate that the paper obviously was not degraded. QUESTION 10 WHAT ARE THE EFFECTS OF ASHING TREMOLITE AND CHRYSOTILE? WHAT HAPPENS WHEN PAPER CONTAINING TALC, TREMOLITE AND CHRYSOTILE IS INCINERATED? When any sample containing treraolite or chrysotile is ashed, the purpose is to eliminate any carbonaceous material which might mask the sample and hinder its examination. However, in order not to affect the tremolite or chrysotile, a temperature is selected which is a safe distance below that which would alter the lattice crystals. For our own analytical preparations, we use 800o f . In an oxygen rich atmosphere, this temperature is sufficient to oxidize the carbon which may be present in the form of cellulose or any other organic materials. However, this temperature is well below that which would affect the asbestos. Chrysotile will remain unaffected until 1382F and tremolite will withstand uemoerarures to x/yb^r. At tnese resDectivs tereDeratures. the minerals will lose their bound water and the crystal lattices would collapse. QUESTION 11 ' EXPLAIN THE HIGH TALC CONTENT IN THE SALT BLANK AND REPEAT THE TEST RESULTS. When we initally began our test program to study the possible migration of tremolite from tremolitic-talc containing paper, laboratory work was performed in an area which also houses many talc-related testing equipment. Therefore, it is very likely that the first few test results (artificial scuff test results) were artifically high in talc content due to airborne contamination. When the first salt blank was reported to contain approximately 8,000 talc platelets in its residue, the laboratory work was immediately moved to an area which would be less likely to contain airborne contamination. Future salt blanks showed a decrease in talc content down to ranges of 700 to 1000 platelets per membrane. In an effort to further decrease this level, modifications were designed into the testing procedure to reduce as much as possible the open-air time exposure of all test components. This last measure reduced the background count to less than 500. The very fact that we could not completely -16-' eliminate the talc background indicates that TEM evaluations of actual test samples may have detected talc platelets which did not come from migration. However, since our December 21, 1973 submission, time has permitted the set-up of a "clean room", in which the background count of airborne contamination is essentially zero. The test results reported in response to Question 9 herein, were obtained from samples which were completely prepared for microscopy in this "clean room". Figure Wo J Figuro No. 2 Figure Wo,. 3 0 Fiaure No, figure No. 5  'fir Figure Ho. 9 tfEXPERIMENTAL PLAN TO CONFIRM PRESENCE OF TALC ON MEAT I. Raw Materials 1. CYCLO-SORB (r*5% Tremolite) 2. CYCLO-FIL (,*30% Tremolite) 3. Lean Beefsteak II. Sample Preparation 1. 2. 3. 4. 5. 6. 7. 8. 9. 10. 11. Make a mask with 5 x 10 cm rectangular opening (50 cm2) using butcher paper or plastic. Put talc into a clean pepper shaker (small holes). Shake talc onto a tared paper and determine shaking needed to achieve approximate weight per unit area desired, perhaps 0.1 mg/cm. Now put a weighed amount of talc into a clean shaker. Place the mask on the meat and coat the exposed area as evenly as possible at about the desired dose. Freeze the meat (uncovered). Determine weight of talc used by difference. When meat is solidly frozen scrape talc coated area with edge of a sharp tablespoon or knife to approximate depth of 1 mm. . Examine scrapings by optical microscopy at 500X. If talc and tremolite are seen make photographic record. Low temperature ash scrapings. Determine optically presence or absence of talc and tremolite and estimate number of particles of latter. m . Report 1. Note presence or failure to confirm presence of tremolite and talc. 2 . If present, calculate numbers of particles of tremolite per cm2 relative to weight of talc applied. S/ Cycto ' S*B 4 % $ 4 - 3 & S M+r b i a n K 4354-3**4' Figure No. 10 a <DOyt 4??4- 3^*6 '/do m Figure No. 11 \ iwvvj \/ O ,\ V ' ( ' VJ X -' V.-' !' ' , ' ''` >,,'i )\\ rtVII7 \X I> m ;i it sruvio:-: r, ,\P M INI S i R A T ! ( XN T O Petitions Control Branch (E F F - ?34 j ! l.-YJ E: Man 3, 1974 Attn : D r . C . Mi 1 as FCA H FROM : Organic and Additives Chemistry Braieh (HFF-144) I S U B JE C T : Johns -M anv i J J c Corporation (J-M) 4/2/74 Data on Talc-Asbt^s cos (T-A) P r o g r a m . We have reviewed J-M's response to the FDA. questions raised on the above subject matter at the 2/27/74 meeting. Our following comments will cover the J-M answers and proposals as numbered in their reply. 1. (a) The food co.ntact area of the purchased containers are provided. However since there was no detection of either tremolite (T) or chrysotile (C) fibers these vms no m i g r a t i o n . (b) The above "no detection" values will i c l a r i f i e d in the following data. The method of mea s r - <en; -neer (a) should be identified. 2. (a) Comparison of lower limits of dcteccobilccu of (T) and (C) by transmission electron microscopy (2 DM} , petrographic (P) and X-Ray Diffraction (XRD) methods will be catried out on T and C spiked talc. The relationship and r e s e t o f the 3 methods will be submitted along wiv.m ePD vs- -.terns and TEM vrints . A statistical analysis of the metha's has b*t-n m e n a c e d . (b) The TEM analysis on the 10 or i 3 css 'em ales cannot run since they have not been retained. !lo\re ,, rbo optical test result data may be available and sho u lc e subivitted if possibl . (c) Under (9) scuffing and shipping tests on nigh talc papers will be run. Possibly TEM analysis on these samples may be h e l p f u l . 3. xhe protocol outlined under (2) should covei our rep vest for Recovery and validation data ---- for the entire analysis at low levels of s p i k i n g '' 4. J-M will attempt - wherever possible - to retain all s a m p l e s , p r e p a r a t i o n s , slides etc. which would permit FCA to chock all data and our method (s) if necessary. am+****ruifiiWHb ajjgi -2- 5. A s noted under 2(b) the 10 or 1 ? cps. samples are not available. J-M d o cs not coniirm our request for a repetition of this test. 6. The complete description of J-M's XRD analysis will be submitted along with sample calculation (s ) of their results on a food packaging paper. 7. This covers our No. 8 question concerning the 6 hour a n o m alous decrease of the talc particles in Table I.V-A, Report E414-2. J-M has no explanation for this result. 8. J-M vrill repeat their meat sampling test - which initially showed no migration. Therefore the spiking and recovery studies with the Cyclo-Sorb and Cyclo-Fil should cover detection at the lowest sensitivity possible. 9. Since the original scuffing and shipping tests were run with papers of lower level talc c o n t e n t , J-M has agreed to obtain paper samples with up to 20% Cyclo-Fil and repeat the saltscuffing and shipping tests previously covered. We would suggest that the scuffing trials attempt to compare the 19 10 c p s . trials. Furthermore these results should be evaluated uiicj iji-a diiu tr ult u j j u u S j.x p,bbJ.i;.LC 10- J-M interpreted our question on the effects of ashing on paper containing T and C fibers to be related to the environmental effects. Our question was directed towards the possible effects on the analysis of samples and not c.i environment. 11. They have not been able to repeal the high talc concentrations in their salt blanks as were noted in Ap pe nd ix 1, p l 2 , Table IV-B. These results will be submitted. The above data also contain a statistical analysis on the lower limits of d e t e c t a b i l i t y . This section should be evaluated by HFF-127 A . Hoitz Johns~K!nnvi!j k .^'*>ci~;jf;orai Ion Greenwood Pinna Donvor, Colorado 8 C c ir Environmental Affairs Department April 2, 1974 Dr. Corbin I. Miles GRAS Review Branch Division of Food and Color Additives Bureau of Foods Food and Drug Administration 200 C Street, S.W. Washington, D.C. 20204 '. Dear Corbin: I deeply apologize for the long delay in my response to you since our meeting on February 27. This delay has been caused by the extensive travel schedules of myself and our research personnel. However, much of the work which we discussed at the meeting has been uj i ue r wHv m r c i In accordance with rhe agreement reached at our meeting, outlined below is our understanding of the eleven questions pot.cd by vou, A1 Holtz and Bill Eisenberg. Following the listing of each question, we have attempted to answer those questions where information was readily available. In all other cases, we have outlined what we proposed to do to provide the information requested. The questions raised were as follows: (1) What is the relationship between the fiber count and the surface area of the container (food contact area)? The areas for the various food containers are as follows: Salt shaking or scuffing test 18.18 in. Macaroni contain:er 88.0 in. Carnation Dried Milk 138.0 in. ; * Quick Rice 160.0 in. Corn Flakes 304.0 in. Morton's Salt 1 45.0 in. *II i Dr. Corbin I. Miles Page 2 April 2, 1974 In the case of all packaged foods we observed no fibers of either tremolite or zhrysotile in the ash residues. In all cases th \ ratio is therefore 0/area. There is no migration. (2) What are the lower limits of dectectability by TEM, petrographic, and XRD methods for tremolite and chrysotile in talc? It was indicated that FDA wants to see a comparison of TEM results with petrographic fiber counts and XRD analyses on various talc samples containing various amounts of tremolite. Further, FDA would like to see positive TEM results on control samples to assure proper functioning of the instrument. To respond to this question, we need to standardize the TEM with talcs containing known amounts of tremolite and to compare tremolite content by XRD with fiber nAnnf e Ktt -f-Tno 'PFxA npfrr>rrrpr>}vi r* p nrciconf 1xt WOJL A - X I H J w x u n a ^x/vczn a ia jJ t c o u t ci lu g u xo r - cc from either tremolite or chrysotile and have added to it knovrn percentages of these two asbestos minerals. These "spiked" samples are than being analyzed by XRD, TEM and petrographic metnods fca determine the lower limit of dectectability by each method and the relationship and results amon<- the three methods. We will, provide XRD patterns and TEM' photographic prints to support the study. A statistical! analysis of the methods used has been prepared. (3) We were requested to provide validation and recovery data (a materials balance) on "spiked" samples samples of tremolite free talc to which we have added known amounts of tremolite. The approach outlined in response t3> question (2) above will be followed. This work will be carried out at levels as close to the lower limits of dectectability as possible, as determined by our statistician. -'"PS- Dr. Corbin I. Miles Page 3 April 2, 1974 (4) A request was made that wherever possible we retain all samples, preparations, slides, etc. Wherever possible, we are doing this. Petrographic slides, however, are not permanent. Immersion oils change with age and exposure to air. We are retaining the negatives for all TEM's. (5) In our salt-scuffing tests, do we have data for 10 cps tests similar to 19 cps tests? Do we have TEM test results at 10 cps? Do we have retained ash samples? Ash samples have not been retained. We have no TEM's for this series - just optical test results. (6) Provide a description of our method and a sample calculation of our XRD analysis of food packaging paper for talc content. A detailed description of our XRD procedure is being prepared. (7) In Table IV-A on page 11, Report E414-2, the six-hour results appear out of line. Can this anomaly be explained? This result is an anomaly. We can explain it in no other way. {8) It was requested that we provide validation of the meat wrapping and sampling tests and the sensitivity of these tests. In addition, relate any migration to meat surface or meat weight. It should be noted that McCrone's results showed no migration. Our proposed response, is to dust a known area of raw meat with a weighed amount of talc. We then propose to scrape the meat to remove the talc, ash this residue and then make a petrographic count of the ash to determine talc and tremolite content. Tests will be run using both J-M CYCLO-SORB and CYCLO-FIL. (9) It was requested that we perform both scuffing and shipping tests using paper with high loadings of tremolitic talc (paper with the highest level of tremolitic talc that is commercially used). Dr. Corbin I. Page 4 April 2, 1974 .es We have obtained samples of paper that are reported to contain up to 20% CYCLO-FIL. This will be confirmed by XRD analysis. If confirmed, we will repeal the salt-scuffing and shipping tests previously reported, using these papers. (10) What are the effects of ashing tremolite and chrysotile? What happens when paper containing talc, tremolite and chrysotile is incinerated? DTA and TGA dat a clearly showed the temperatures at which the hydro xyl bonds are broken in these minerals, Tremolite goes to diopside, chrysotile to forsterite and talc to cli no-enstatite. After burning paper containing triese minerals, they would all be altered. As indicated at our meeting, a good incineration system would provide r eat in excess of 1,000 degrees and at 700 degrees, t: emolite and chrysotile are destroyed. We are presently preparing an environmental impact analysis report tor use as >acJc-up tor FDA's usea is: "incinerator buiaennes" oy uewarco, neioe, Leckman and Newton; 1969, U.S. Department of Health, Education and Weifare, Public Health Service. (11) Explain the high talc content in the salt blank and tepeat the test results. This test was repeated several times and with each repeat test we failed to find the high talc concentrations originally found in the blank. Documentations of these results will follow. During the meeting, you requested a statistical analysis on the lower limits of detectability as prepared by our statistician This document is attached hereto. As we indicated at the meeting, it will require a period of approximately two months to perform all the necessary work to respond to all of the above requests. Hopefully, this information should be available by the latter part of May. We appreciate very much your indication that FDA will make no final determination with respect to the proposed talc regulations until this work is completed. tor- Dr. Corbin Page 5 April 2, 19 74 Unless I hear otherwise from you in the near future, we will proceed with the work outlined herein. Again, thank you very much for your cooperation and assistance in this matter. Richard P. Carter, Director Government Relations RPC/emr Attachs. April 2, 1974 FIBER COUNTING STATISTICS In all counting techniques it must ba recognized that a single numerical value reported re presents an estimate of the true value from some range of possible values. The range is dependent upon such factors as how large a number is expected and the number of fields counted. For low concentrations, it is valid to assume that the particles, or fibers, will follow a Poisson distribution. Based upon the above assumption, there are several ways in which the statistics of counting fibers can be analyzed, and a complete study of the problem will be presented at a later date. For preliminary consideration the attached graph shows the expected variability for counting fibers in a one milligram sample of talc. It is based on the assumptions that the sample covers an area of 324 mm2, one "field" represents 0.096 mm2, and that the number of fibers in 100 fields are counted. The limits shown around the "expected value line" are the 95% confidence limits, ** *& -; Q ^ i that fiio -frim. v a l u p w i l l | h p f - w p o n -f- h q pi f rm f* cj _ _ j-l:J l.'iiVV Ll-J L 1, -t 'Ll' TA/><Tv- 'y'Aorw~L "" ;.7^ .`\:i. tO <'pY ,C< i ! ---- t - - .:rr -M /Y- ~r J'J !:I ;i < ;\:~v i . t I ~ !" i TT Ii ] : i: Ili----^r j I X a i& 1 5 y V t , '- C r .r te r , Teure; - I c/o j . en vil.-f t . f u Je;;. I..-.-o ,, '"o IotoC ''!7 .. Ser l Yvt *" Mr tC'fdv.'V 'r r* }* " ;*v-fiv*r**~r n'OtjJ* f'TCt*??C s - . - ' ~ "1J `jt -i' * `- - L 1 v. ir : cirri ilertion. Aj 5 ,.J; e ter i r t r e .itr.cV rd rc-.orcndu. * 're .rf erye-cilu-; ex c-t r .. . , t/uvJ v :..:, tns l;M e r u t v . r l y t:.e ; r l c / *.{fc t .StJLO* o C.U l. ,,u i ^ i m a ritir m i tire to i-r,;-rtrrOo tier, rer'r, :ret ly to r-e. tir.cf ruiy yonv..t ; crm Ce i ' 300 j . T - 330 "IT-335 CT)rile t:pch:4-3-74 c;,:, Divi; '.urie u Between: C o r b i n I . ; ' f. William V. ' Albert Vol (;x ; f.v , !TC4/!TF i-rroeralyticnl French, r 5,/FFF nic osift Additives ranch, DCP/LPF end Richard Carter, Jo'"v>"x.7tnville Richard Lenar, Jo o s -'a n v il]e J it* I e i - o v ? l c r , .Jo - : r .- K a n v i ll e Subject: ?rirration TX D<.i;i: n , 3973. cy *. * . ' by Jobp3-"fanville, in Cos voi'ts or tc IP. Frcr'csal of Cetstenbnr 2V>, 19/3, l;r. Vi l ; requested this nocti u to seek clarilicet icn of numerous q*;e.*;l. cri r.li . ..en ;PA revir ; r . to. - ,,'j-'Ct convents. Tbs oueetdens recursci cir.v L o ;ticn, represent consolidated questions of the above 3 k persons The. ex..:, "fore, and clarification requested of the above Joar.s-ksnvilie persorr.ei weie: C; 1. }DA jc-rcf-nnol need data relationships of. fiber counts observed versus fore! car tact area or box rca, etc.. 2, Mo. vent a eompariron of transmission electron microscopy (Tb.l') iirfrl rf-lTft''T/r**n*jC' rr>r,-i t<pmi MviHinti . 'i-uinSd hf nnn# rm d.irn! of sxr.il,or origin and should indicate ] . ... u rirdinns by T'dli to assure proper functioning of this instrument. a) Standardized TRH with known trr : ' t talc. b) Do TEli analysis on 10 cr 19 cps i.x; ..pies, if possible. 3, Recovery and validation data should be generated for the entire analysis at low levels of spiking. 4. J-ii should keep ail reserve sarplru v tents. FDA may have to check our method * 5. he would like to see detailed data for t sir.Liar to the 19 cp.s data. J-;l will repeat to evaluate by TRH. ; from ncn-Ucscructivu r::> used by J-II. . ....t c,: \ ;an 6. L'e vent a sample X-ray diffraction calculation to J*. to the percent talc in papers (rorton salt sample as an exarpic; . 7. that is the Valley abrasion test? This question was answered satisfactorily. Thy is there a decrease in residue values in the -12 hour interval recovery and v~!1h *-yi data should bo renerated for the J-M v.\".i: to..-. . I'-"-. All tnt.-! retort ; e.r.'se corr.ontG 'ere cn papers containing p :o:; Lt. ioi" lb. t: 1 c a /or pitch control, 1.1 at about hi phi/ Ci'l'-rdorou r.,:i.or con to.A `up bibber levels of talc? J--M aprceo to test roi'o or those caper i also. 31. F.-A concern r r -p--- cd for the data on the salt tln'-dc in / p -llx 1, r>. 12, ' j . If salt birr.!: eer tains annrori r>ntolv - .11 ;rr>, \ :j are 4.... . . ..t. observer, in analyzed sarnies usinj? t-; 12, Theta crnresrrd as rorrihlc* trace.1 should re: tore mplicit. hr. < ;t :r ashed ho" lone !T-\ could five Johns-TTarvl jlc> to vork 0:1 th-'- prebi ;, sttbrit further data, and clarify thorn r|ror. tiers? :',r, rile-3 rain ic r.h. ht other evaluations vould tod o rc'rrcr:; t -iy tvo w'Oat.>v. e ' l F t v store vast J--'i ouc'iticvrnl tnta af cut the r*-j of Apr3.1 . J- r -<.('] uboti ht t* at these r - y e tot 1or-s var*-1 rr--.ron.-P*'*o , Hr, C--3 i.-r a-'-." to nrenare J - M 'r ttcrorT'drr of this roctinp, indicr.t tb.oiu ,\:r'.tr.'/, .'ey of FDA questions ashed. Respectj.:.v iy nubr.itted, cc; 330 ,5J> Gil;11c 4-3-74 Corbin I. lilies, rh.D GPA51 Iloviev branch fjSAS Rcvl Francb , ffT -*\'iC f.ttn: Dr, C. 'l i d s February '0, 197 Organic an' Additives Ch e n l s t r y C r u n c h , H!:F~1 ' J o h n s n v i 11 o tett e r 12/21/7' 'to,' d t a on Asbestos in Talc. In 0 or c-' -In at 1on of the- ;-ji-rp t.if r> 0 T 1n >aper ; *>/10 ! vc h ave rev io'ip*{ * f' C iK Iifm)%>J"'1!o O*'<rj -''**If'stns f ro ' '-0 ]c -1 .ids'.s-.Tanv 11 ii. dtVii"& u " Tho firs; n t*S *,J<air. {*1/: : /y ccv rod in 0 or W d /'/: accor ->M '>|n n V_:ta i1 s } \ *5 This \v J ~a t nc ir ,i`-Vi'1at In $ lu ,v{jics for aq .e o u s a ji ! iCit.0 t``ous hv 1 i :r-'-raiih nach 1r,p tr 0. >>>r5s f?nf-rj*v t ^ r>fs p.f;i ' oat V\1 1 0 n<; v^ cur ;, 1 - -{*1 T -r-o ':1r*t* 3 nuusc r o f n f .VV/iv\'. s Jno t'-ir. tus t if>'* 0,1iiu* uot lz U 0 1r our s ta nc dro c x fr a d i o s os tinp for sol s ~ f cranes. ,, . . 5- ^ t v , JUJ . i. W W 1 t I V . v* V V VM I lj ecn^iriii m varo stive mgra;. icr. ca i.a ror i.~u ioi luwnrj rn ss osis : 1. " '.cost.;'! r-nrsrs * pri e h a d n a a p p l i c a t i o n s are r<ost.ly dovor-vj to dry fo*' -s so-,ich sbutil d there-fore result In abr.35 ve ctiec on tbo psper. 2. Any viet or nolst food oackcclnn applications are no nor a 11 y rin hlnhly coJ on os red papers arid are of snort tiro *>orices. Pa c e*df *'oe\ne the 1 the a o iurn el ;ovi bove re asoI 1 1o n rvi if:, ti i!' O'rdrr of nc cor consi n ! vould ran si c n f H c a o c v de : * rati the on 0- ~f ,; the talcoval i:a tic tt* Testi f!rj (sr artoal p- cre^-'-'T foe hs (salt, vacarotsl, dry niU;* rice* arui corn ''lores), b. Results of nickanad salt s h i p p i m tests, c. Laoojoitory de-rf f K pneiaoinq tests. d. V.oat pack v 'inn tests. I '> :: <* s i Or> t :';"r ` ,, 'ir 1 / ,r- ?/2)f't ' * .veti ^ :-s* r-?/ : ''ny1 <; r1-f t -r- fSj , ; 7 .- '', T: o V i 1''i of U1'J :"1*;J-- - t \. 0'1 ^rt. 'i'O- ^V r*- t ", J s .1 \.\-V'*.***1iT-7 0 t!ic : 7 0 i *l,, %i'.< -fw) '*i.*iti.-'.fJ\f1c*^'^> `'ie.. r f o rf?stjn t? 1 1 V o % -*4 ... i, 4*J ,> V . `3 V1 i)f f;H - :*/J :;i t ; ", rV "V'*' . rMtz ?n:rr:r*7* *,>t/? ^:ol le :een 2/26/74 V,. o 1974 !: l e ' . * o \-r.il.-: r Di r c.c i !. r , C r c ;r j . r.*: i : i ' J o h n s - i ' a n v i l c " o r ":: ; d -'-o C r e r u m ; od F ) .re: a Donv e r, C r L o v a .* o - '/ `; 1 . O'Mr "r. Car l.'e* have yoni o' -J 1 c o r m o n f i r - ' ' ir) ' --; f o '' :>r / public h--d in tno ' V.. - - 5 rrj ri;o K e.'triij`v C l c r -'.'.r ; 'in Food mid Dono," .bc-r ?!\ ?.r*73 (30 PJL. 27076) T.*e a p p r e c i a t e y . n r co- - c u r o ;*r. i > i : 1 r:o r a f o r the:-. c l o u r v i t l i o t ic-ro r o c c - i ve o' j.r -oo r r a r . : . a roer-, - <-o i c i . i o n "'-r f irvi I m t j o u i n th3 r a t t i 1! M -.'in 'r1' i v r,\ r-.. Cm'h'o 1. `in*"?, ?h.D. ry/.O "mvi.-v 'r.-noh Division of food and Color Additivo ".aromi of Foods c c : IfrT-300 ]iT'F-;r;o lV--315 - r o u f Fri Lo C Kli] e o : dbb :3 -12- 74 { Johns-Manvie Prcducts Corporation Greenwood Plaza L'envoi, 'dolore dt 80717 (303) 770-1000 December 21, 1973 Hearing Clerk Food and Drug Administration Room 6-86 5600 Fischers Lane Rockville, Maryland 20852 CERTIFIED MAIL RETURN RECEIPT REQUESTED Dear Sir: I am responding in behalf of Johns-Manvilie Products Cor poration" ("J-M") to the Food and Drug Administration's (FDA) Notice of Proposed Rul : Making relating to asbestos particles in rood and drugs, as published in the Federal Register on September 28, 19 3 (hereinafter referred to as the "Proposal"). - > indicates fha.f or ueiuiK jjeuexujex i J , 7n e wx-cn m e nearing exert, written common vs regaro.ing the petition from the Center for Science in the Public Inte rest and the Environmental Defense Fend and the Proposal. Desert Mii^ra.js, p.c, an affiliate of Johns--Manville Products Corporation, is a major producer of crude and processed rale, a suhstantial portion Ox V7hich is sold for use in the manufacture of food and drug packaging materials. On April 20 , 1973, J-M forwarded to FDA. a letter with attachments containing comments to proposed regulations covering the use of talc in fooci ?.nd xooc packaging ma terial, as published by FDA in the Federal Register on August 12, 1972. It is reguested that those comments be incorporated as part of the record with resoect to the Proposal. The Propo L, as it relates to the use of talc, differs importantly from the earlier FD.A proposal in thixx. FDA` is now additionally proposing a restriction on the use of talc containing asbestos fibers in 'any drug, drug ingredient, 0'r drug pastaging material." Hearing Clerk ,-3- December 2 1 1973 packaging applications. United States paper manufacturers import significant quantities of pulp from Canadian and Scandinavian producers for consumers in the U. S. Packag ing materials and packaged foods and drugs are imported from many areas of the world. Thus, the Proposal adverse ly affects the entire worldwide pulp, paper and packaging industries. Therefore, limitations on the use of talc cannot practically be restricted to only food and drug packaging materials. It should be noted that the only form of asbestos found in J-M talc is tremolite. J-M "CYCLO-SOBB", which is used for pitch control contains 2% to 5% tremolite by volume and J-M "CYCLO-FIL", which is used for high bright ness filling, contains 20% to 30% tremolite by volume. Some highly tremolitic talcs, such as those from upper New York State (which contain as much as 60% to 70% tre molite and some traces of chrysotile) are too abrasive for use in the manufacture of pulp and paper. The Valley Abrasion loss with these products is well over 100 mg. Any talc addition which results in a Valley Abrasion loss nvpr j \) ma. is imoracncai to use. xnese iumiixv Lrcmuxj.tic talcs, with possible traces of chrysotile, have been tried and rejected for use in the paper industry. Use of commercial talc in the manufacture of pulp and paper in substantial amounts was begun approximately 15 years ago and its use has incresed enormo isly during the period. As used in these processes, talc bewomes an integral part of the pulp and paper formulation. As such, the talc be comes locked into place in the paper. Talc is never dusted dry on the surface of the paper. Use of Talc for Pitch Contro1 In the 1950's, a study undertaken as to the fundamental properties of talc, and particularly its surface charac teristics, showed that the mineral talc is virtually unique among mineral substances in that it is strongly hydrophobic and organophilic. It is capable of adsorbing various kinds of organic, fatty, or resinous materials in the pre sence of large volumes of water. When added to a latex, it will selectively adsorb and rob the latex of its sta biliser system causing the latex to gel. Latex stabili sers are generally either anionic cr nonicnic surface active agents. These are fairly high molecular weight compounds with a hydrophobic end and a hydrophilic struc ture at the other end of the compound. Hearing Clerk December 21, 1973 industry based largely on fishing, has recently required mills to close up their water systems and to limit the use of surface active agents. The use of talc for control of pitch is the only feasible alternative. When talc Ls used for pitch control in the pulp mill, colloidal pitch particles are adsorbed onto the surface of the talc. The talc holds the pitch in a finely dis persed and innocuous state preventing agglomeration and deposition on the machinery. The talc with its adsorbed pitch remains locked in the pulp or paper. The pitch itself aids in binding the talc into the paper. The use of talc for pitch control has grown very rapidly worldwide. Talc is now used in most pulp and paper mills throughout the United States, Canada, Western Europe, Scandanavia, Japan, and in all other major pulp and paper producing areas, solving a problem that had plagued the paper industry for years. No other product works as well under such a variety of conditions and at the same time, solves major stream pollution problems associated with paper production. Pitch control is now the major use on certain grades of talc. The rate of talc addition for pitch control will vary with the severity of the problem, the type of pulping (Kraft or sulfite), the kind of wood, the age of the wood, time of year, water temperature, pH, etc. In the pulp mill, talc is added just aheaa of that processing step where the pitch first begins to appear. Under these conditions, the talc is present to adsorb the pitch as it is released. If the talc is added later, after the pitch has started to agglomerate, it is not as effective and higher rates of addition are needed for control. Normal rates of addition in the pulp will vary from as low as 0.25 per cent to 1.5 percent, although additions of up to 5 percent are infrequently encountered. Talc introduced in the pulp mill is carried over into the paper mill as an integral constituent of the pulp. As the pulp is further refined in the paper mill, more pitch is released and additional talc must be added for control. Here the pitch is in a more agglomerated form requiring higher rates of talc addition. Paper mill addition rates are normally between 0.50 percent and 2.0 percent. Hearing Clerk -6- December 21, 1973 Use of Talc as a Functional Filler Talc is also used in the paper industry as a functional filler. In this use, talc is added in the paper mill to increase the brightness and opacity of the paper. It also makes the paper smoother, more amenable to calendering, and more receptive to high fidelity color printing. As with the pitch control use, talc for filling is beat up with the pulp and become's locked in as an integral part of the sheet of paper along with the cellulose fiber, resin size, clay, titanium dioxide ("Ti02") and all of the other parrs of the furnish. In this use, talc can and is being used to replace a portion or all of the Ti02 in some papers. Although heavier load ings of talc are needed to develop the Seine opacity as Ti02 . This application is becoming more important as Ti02 is in critically short supply. For high brightness filling applications, up to 15 percent loading might be used. Normal rates of addition would v> ^ ys K i.T v s [T ^3 T A X- --' _l_ n ^ ---- O f ~^ 1 J- oi ury paper puiu. m axx cases, m e rare xs incorpora tec. wet into the cellulose fiber matrix. High brightness opaque papers containing talc filler are generally a high-grade paper typically used as stationary, memo, bond ledger, off set, duplicating and publication paper. The use of such high-grade paper in food or drug packaging would be most unusual due to the relatively high cost. Talc is infre quently used as a filler in food and drug packaging ma terials, as brightness and opacity is not of primary con cern in these paper applications. Use of Talc in Recycling Paper Of increasing importance is the use of talc in the deinking process for recycling of paper. In this application, talc selectively adsorbs the oil and resin which serves as the vehicle or binder for printing ink and other residual or ganics. The ink is then flushed from the waste stock, leaving the residual organics bound to the talc in the waste stock. The talc also controls the agglomeration and deposition of latex binder and impurities found in the waste paper. Waste stock containing talc is then added in varying degrees to pulp for production of finished paper. The percentage Hearing Clerk -7- December 21, 1973 of waste paper which nay be used in recycled paper is increased dependent upon the effectiveness of the deinking process. Thus, the use of talc permits a much greater use of a wider variety of waste paper in the furnish. The increased cost and shortage of pulp, as well as ecological considerations, dictate the increased use of waste paper, necessitating greater use of talc for that purpose. Surface active agents, while useful for these p u r p o s e s a r e l'-ss effective than talc and have adverse ecological impacts as indicated above. Use of Talc as a Direct Food or Drug Additive The vital use of talc in the manufacture of pulp and paper should be contrasted with its use as a direct addi tive in food and drugs (such as dusting chewing gum and as a tableting aid) . In these latter applications , talc does not serve a vital and valuable function, adequate substitutes for talc are readily available and a restric tion on the use of talc as a direct additive would have little if no adverse economic consequences on the U. S. talc industry or the food and drug industries. However, indicated hereinafter, the use of talc containing tremolite, even as a direct food or drug additive, poses no real health hazards from ingestion. 2. TREMOLITE DOES NOT MIGRATE FROM PACKAGING MATERIALS TO FOOD OR DRUG CONTENTS ' Studies performed by J-M and independent consultants and reported on in J-M's prior comments conclusively demonstr ated that any tremolite contained in talc used in food packaging materials does not migrate to the food. As a result of the raw meat wrapping and sandwiching freezing tests reported in our earlier comments, no tremolite migration at all was detected. As a result of J-M's discussions with FDA, J-M conducted further migration studies to determine whether or not the possible abrasive action of dry food substances or di'ugs would result in the migration of tremolite fibers from packaging paper containing tremolitic talc. In de signing a migration test capable of producing scientific ally valid results, J-M consulted with Mr. Allen Spi'ner, Chief, GRAS Review Branch, and Mr. G. Higgenbottom of FDA, who provided certain test guidelines. Hearing Clerk -8- Deceiriber 21, 1973 The initial study of dry food abrasion requested by FDA is set forth in Report No. E414-2 from the Johns-Manville Research & Engineering Center, a copy of which is attached hereto as Exhibit I and referred to as the "scuff test." The "scuff test" was designed to determine the extent to which tremolite fibers contained in talc used in the manufacture of paper for food and drug packaging applic ations might be expected to migrate into food or drugs with which it would-come n contact. The test conditions used were arrived at after considerable discussions with FDA. At the suggestion of FDA, salt was used as the medium for the scuff test, since its sharp edged cubic crystals would act as a more abrasive material than any other dry food substance or drug. The test was "arti ficial" in that it was designed in an attempt to dupli cate, in a laboratory, the conditions present during actual commercial shipment of food and drugs. The test consisted of lining glass containers with paper manu factured with tremolitic talc, partially filling the containers with salt (NaCl) and vibrating the containers for a period of 24hours on a shaker tester. -- *-- < _1 - -- 1. -- I -T* J! .. n J -- J-- M. J_ t-- .m J- -- . r. X /s /-- 4- -- .t v 1 - f-* V v /*V ^ X* V \ --V *4-- migration of tremolite did not occur in the absence of partial destruction of the paper itself. When partial destruction of the integrity of the paper occurred, the resulting migration had the composition of the paper inso far as could be measured, indicating that tremolite does not "dust out" or selectively migrate from the paper. At a frequency of 10 cycles per second (a frequency equivalent to that of a freight train having a flat spot on one pair of its wheels, traveling almost 60 miles per hour) no evidence of paper breakdown was detectable and no tremolite migration whatsoever could be detected. Only when vibration was increased to 19 cycles per second did substantial breakdown of the paper occur after 24 hours, with resulting migration of all components of the paper. Additional testing was performed to determine if during commercial shipment of food and drugs, the vibration and movement actually encountered results in abrasion suffi cient to cause the partial breakdown of the integrity of the paper packaging materials. The second migration study performed is contained in Report No. E414-6 from the Johns-Manville Research & Engineering Rearing Clerk -9 December 21, 1973 Center, a copy of which is attached hereto as Exhibit II. The test consisted of lining containers with tremolitic talc containing paper (identical to that used in the test described in Exhibit I) and shipping these containers which were partially filled with salt by commercial truck from Denver, Colorado to .Manville, New Jersey and back (a round trip of approximately 72 hours and 4,000 miles of travel). The shipment of these test containers of salt resulted in no breakdown in the integrity of the paper and no migration into the. salt of tremolite or any other ingredient of the paper. In addition to the salt shipping test, a variety of dry foods packaged in paper containing tremolitic talc were purchased at a local supermarket and examined to determine whether migration of tremolite had occurred. This study established that tremolite contained in talc used in food packaging does not migrate to any dry food substances during normal commercial shipment and handling. The food purchased at a local supermarket showed no evidence of tremolite migration. This was so even though foods were chosen which were likely to have been shipped long f H S ' f ' R n r ' P i p -p r3 r~ I n l r ^ l w +~r\ "K o 0511 '-'V* o q Ct. C y~'P On the basis of studies reported in Exhibit II, J-M has concluded that actual commercial shipping and handling conditions of packaged dry foods does not cause suffi cient abrasion to the containers to result in the break down of the integrity of the paper or migration of tre molite. The latter tests (Exhibit II) establish that the conditions existing in the scuff test (Exhibit I) are indeed much more severe than actual commercial shipping and handling conditions. In Exhibits I and II, results are reported to the re liable levels of identification by optical (petrographic) microscopy and weight determinations and with the addi tional use of transmission electron microscopy in Exhibit II. The shipped salt samples and the purchased food materials were first examined by petrographic methods as recommended in the Proposal. Over 100 fields of view were examined for each sample, with considerable effort exerted to identify the possible presence of talc or tremolite. Hearing Clerk -1 0 - December 21, 1973 In addition to the petrographic examinations, the samples were also examined by transmission electron microscopy. Each entire sample was scanned in its entirety for sus picious particles and fields were chosen at random for specific counts. However, even following these stringent analytical pro cedures, the presence of tremolite could not be detected. It is evident to J-M as a result of the studies reported herein, that actual conditions of commercial transpor tation do not create a severe enough environment for ^ paper breakdown to occur, and the migration Oj_ L.reroolite from paper containing tremolitic talc used m rood and drug packaging applications does not occur. 3. NO EVIDENCE FEISTS OF A HEALTH HAZARD ASSOCIATED WITH THE INGESTION*OF TREMOLITE___________________________ In r-M's comments dated April 20, 1973, at was stated ^that there is no evidence whatsoever to indicate that the inges tion of tremolite constitutes a health hazard. Tremolite cannot properly be considered as a "poisonous or deleterious suiib ucuiutA eon ueiupid L.eu in in stuLiua fiuzia) m Oj. rne Food, Drug and Cosmetic Act. The studies wn.icn have sug gested that the ingestion of asbestos fibers may be car cinogenic are based on substantial occupational exposures to ether asbestos minerals, and not to tremolite. In the animal ingestion and inject: on studies and human epidemiological studies of talc woikers, cited in J-M's April 20, 1973 comments, no excess incidence of gastroin intestinal cancers have been reported. Animal studies involving tremolitic talc have been conducted by Dr. William E. Smith, Health Research Institute, Fairleigh Dickinson University, Madison, New Jersey and by F. fort and Friedrichs in West Germany, both of which studies were reported by Dr. Wright in Exhibit F to J-M's April 20, 1973 comments. Pott and Friedrichs introduced tremolitic talc directly into the mesothelial spaces, which failed to produce mesotheliomas, a finding in contrast to,the production of mesotheliomas using other forms of asbestos. Dr. William E. Smith has both fed chrysotile and amosite asbestos to hamsters and has administered tremolitic talc by Hearing Clerk -11 December 21, 1973 intrapleural injection to hamsters. A summary of Dr. Smith's findings is attached hereto as Exhibit III. Dr. Smith's findings are as follows: "In 45 hamsters maintained throughout their lives on diets containing 1% of the chrysotile or amosite varieties of asbestos, we found no gastric carcinomas and no tumors in the gastrointestinal tract except for a neoplasm in the mesentery of the colon. We are unable to relat* that lesion to the treatment, since ashing has revealed no asbestos fibers in it. We have now completed an experiment in which the liampster intrapleural method was used to test for carcinogenicity of a sample of talc containing asbestos. For this work, we have obtained samples of commercial talcs from Whittaker, Clark & Daniels, Inc., New York City ... X-ray diffraction analysis revealed the presence of major amounts of tremolite asbestos and talc and a minor amount of a serpentine mineral (antigorite). -- ^-r trn t-- -- ~ l i i T - Z T C L p 2.CHITCl2. injection or o mg or t m s samp re suspended xn 'J.a ml saline. The animals were followed for their life spans. No tumors attributable to the treatment were found." In a meeting on December 7, 1973, with Dr. Virgil Wodicka and Dr. Albert C. Kolbye of FDA, a copy of Dr. Smith's Terminal Progress Report: Grant No. 3R01-EC-00226-045I entitled "Mesothelioma in Relation to Asbestos" was deliver ed to them. Among other studies, this contained his find ing that long fiber tremolite injected directly into the pleura space of hamsters did not produce mesotheliomas, whereas other kinds of asbestos used in similar amounts did produce these tumors. A copy of Dr. Smith's Terminal Progress Report is attached hereto as Exhibit IV. J-M's comments of April 20, 1973, cited the study by Dr. Morris Kleinfeld of talc miners and millers exposed to talc .containing extremely high concentrations of tre molite. In this study, Dr. Kleinfeld concluded that there was no significant difference between the observed and the expected mortality from carcinoma of the gastro intestinal tract and peritoneum among these talc workers. Also included as Exhibit G to J-M's April 20, 1973 comments Hearing Clerk -1 2 - December 21, 1973 was a copy of a letter from Dr. Kleinfeld dated January 24, 1973, reporting the results of his follow-up study of these talc miners and millers. Dr. Kleinfeld concluded in his follow-up study that "With regard to cancer of the gastrointestinal tract and peritoneum among the talc workers, we did not find any significant differences be tween the observed and expected values in the overall and specific age groups studied". i This follow-up study has not yet been published, although Dr. Kleinfeld has advised us it has been accepted for pub lication. In view of this fact, and the importance of Dr. Kleinfeld's work, J-M has obtained from Dr. Klenfeld a paper which he presented at the Metal and Non-Metallic Mine Health and Safety Symposium on Talc Dust Hazards sponsored by the Bureau of Mines and held in Washington, , D. C. on May 8, 1973. A copy of this paper is attached hereto as Exhibit V, and summarizes both his earlier study and the follow-up study. It should be noted that at the recently held EPA-NIEHS Joint Symposium on the Bioloaical Effects of of rtsucauus . or. toiii r Ct"-'fh mor.rrc. . ,, xj oiumai ieea- ing experiments, in which he fed quantities of asbestos to hamsters with no resulting gastrointestinal cancers. After reporting on his animal studies, he then posed the follow ing question to all those in attendance at the Symposium: "Was there anyone who has conducted animal experiments where asbestos fibers had been ingested (including inhalation studies) and observed any evidence of gastrointestinal cancers?" There was no response received from anyone in attendance at the Symposium and no evidence was introduced at that Symposium to indicate that any animal ingestion studies involving asbestos had resulted in the development of gastrointestinal cancers. It should also be noted that to the extent that tremolitic talc has been used in dusting chewing gum and in prepara tions of oral medicines, the public has participated in a large scale ingestion study over a lifetime. If one thinks of ingestion of tremolite at this level as being hazardous with respect to causing mesothelioma, why is this such a rare tumor, occurring at a rate of 1 to 1.5 per million population annually in the public at large? This sort of exposure dates back to the beginning of the century. The ingestion of fibrous tremolite in this manner would ex ceed any possible potential from the use of packaging ma Hearing Clerk -13- December 21, 1973 terial containing tremolitic talc for food and drug packag ing applications. Evidence offered by FDA in its earlier proposed regulation on talc (August 12, 1972), to support the proposition _ that ingestion of tremolitic talc is hazardous, is limited to an article by Dr. R. R. Merliss in Science (September 17, 1971), in which Dr. Merliss attempts to show a causal relationship between the use of talc-polished rice and the high incidence of gastric cancer in Japan. The data used for this purpose is spurious, to say the least. Dr. Merliss, himself, now doubts his conclusion as is indicated in his recently published article entitled "Talc-Coated Rice," Life and Health, March 1973. A copy of this paper is at tached hereto as Exhibit V I . No medical-scientific evidence was offered by FDA in the latest Proposal (September 28, 1973) to prove that the ingestion of asbestos, and particularly tremolite, is injurious to health. As a matter of fact, the studies cited by FDA in the Proposal indicates that ingestion is not injurious, based on the animal studies reported. IT C Ll*vL. m v - v l .L O U j. J P ^ . C i U . J . l . i . 0 L U im L lU lllL ^ 1 1Cl XU X U U U. that asbestos, when ingested, is carcinogenic. Even in those studies where there is some suspicion that ingestion of asbestos may result in a higher incidence of gastroin testinal cancer, this suspicion arises only in cases invol ving individuals most highly exposed to asbestos in occupa tional settings, and the asbestos being forms other than tremolite. The Center for Science in the Public Interest and the En vironmental Defense Fund in their petition submitted to FDA, do not introduce any evidence whatsoever tending to either incriminate tremolite or to prove that tremolite will migrate from packaging materials. The studies cited by these two groups in their petition relate to insulation workers most heavily exposed to asbestos in occupational settings for prolonged periods of time. As indicated in J-M's earlier comments, these studies may not be validly related to tremolite. One cannot assume that all forms of asbestos will react biologically in the same way and one must also recognize that there is a dose-risk relation ship with respect to exposure to asbestos. Even in those studies of individuals occupationally exposed to asbestos, there is a substantial dose tolerated by occupationally Hearing Clerk -14- December 21, 1973 exposed individuals before evidence of any possible excess cancer experience develops. These two groups in their petition fail to cite any studies relating to the effect of ingestion of tremolite. Such studies are conspicuously absent from the petition. 4. THE FDA PROPOSED TEST METHOD IS NOT WORKABLE In its Proposal, FDA has proposed a test method for deter mining the presence' of armestos fibers in food-grade talc. The Johns-Manville Research Center believes the test to be unworkable on both practical and technical grounds. This belief has been confirmed by independant consultants. Attached hereto as Exhibit VII is a test method which is a modification of the one proposed by FDA and which, in the opinion of J-M, is a more suitable method for deter mining the presence of asbestos fibers in food-grade talc. However, it should be noted that J-M's talc does not meet the FDA proposed test method, nor the one proposed hereiia, and the talc of most other talc producers falls in the same category unless the limits of detectable tremolite are Conclusion In conclusion, we have attempted to respond in our comments dated April 20, 1973 and in this document to the issues raised by FDA in its proposals published on August 12, 1972 and September 28, 1973, with respect to the use of talc containing asbestos in food and drug packaging materials. J-M believes that the use of talc is essential in the manu facture of pulp and paper and is ecologically and economic ally desirable. Tremolite does not migrate from tremolitic talc containing paper packaging materials to the food or drug contents during commercial handling and shipping. The is no credible evidence indicating a health hazard due to the ingestion of tremolite and there is conclusive evidence that the ingestion of tremolite by humans and animals and the injection of tremolite into the pleura space of animals does not result in an increased incidence of gastrointesti nal cancer or mesothelomia. It is submitted that on the basis of all known facts, ad option of the Proposal would constitute an arbitrary and capricious action totally in conflict with the best scien- Hearing Clerk -15- December 21, 1973 tific evidence and needlessly destructive of the domestic talc industry and disruptive of the world-wide pulp and paper manufacturing industry. As there is no justification for imposing any restriction on the use of talc containing tremolite ..n food and drug packaging applications, it is urged in the public interest, that, no cause being shown for its adoption, the Proposal severely restricting the use of tremolitic talc in food and drug packaging material, be withdrawn. . Very truly yours, Richard Carter Director, Government Relations Johns-Manville Products Corporation REFEREN CES (1) Pott, F. and Friedrichs, (1972), "Tumors in Rats After Intraperitoneal Injection of Fibrous Dusts" (German). Naturwissenschaften 59: 318. (2) Smith, William E. (May 1973) "Asbestos, Talc and Nitrites in Relation to Gastric Cancer" American Industrial llvqiene Association Journal, May: '227-228~. (3) Kleinfeld, M . , et al (1967), "Mortality among Talc Miners and Millers in New York State", Archives of Environmental Health 14:663-667. nkFIBIT I Rcoort^^ E414-2 Date December 12, 1973 Title: PRELIMINARY STUDIES OF FOOD CONTAMINATION BY CONTACT WITH PAPER SUMMARY A study was undertaken to determine the extent to which the tremolite fibers contained in talc used in the manufacture of paper for food and drug packaging applications might be expected to ''migrate" into .food or drugs with which it would come in contact. For these studies, a test method and procedure were worked out which established that the migration of tremolite contained in talc used in food packaging paper occurs only after partial destruction of the paper after being in contact with food. Without some destruction of the integrity of the paper, no migration of tremolite occurs. When partial destruction of the integrity of the paper occurred, the resulting migration had the composition of the paper insofar as could be measured. Partial destruction of the integrity of the paper and migration cf the component elements of the paper occurred both O C U tlp J-U J O V U U l .- i i - i i j O .L c m v j u . J . U O - .O f U RT. C i3 X U L .lt ; LU C J .U U U U kO U contained a similar proportion of talc and tremolite fiber. Since talc usually constitutes one percent or less of the total paper, talc migration is so low as to be barely measurable and tremolite fiber levels could be three orders of magnitude less. The test condic. ons used here were arrived at by discussions with the Food and Drug Administration. Additional testing must be undertaken to determine whether or not the test conditions used herein actually, in fact, duplicate the conditions and what takes place when food is shipped commercially, so as to determine whether in commercial shipping the partial destruction of the integrity of food packaging paper occurs. Contents: Summary, Discussion, Conclusions, Recommendations,'and Appendix I, II, and III. Reported by: R. J. Zazenskr k jm Report. Page E414-2 1 DISCUSSION Introduction FDA on September 28, 1973, published a Notice of Proposed Rule Making which would restrict the use of talc in food, drugs, and food and drug packaging materials. The proposed rule would pre clude all such uses for talc, if the talc contained more than specified numbers of chrysotile and tremolite fibers. Talc is widely used as a pitch control agent in the initial manu facture of paper pulp from wood, and also in the actual manufacturing of paper. Talc so used, becomes an integral part of finished paper produced from this pulp. The finished paper, which may also contain various other special purpose fillers and pigments such as clay, whiting, and TiO?, etc., is used for the full spectrum of paper applications, including food and drug packaging. This study was undertaken to determine the extent to which the tremolite fibers contained in talc used in the manufacture of paper for food and drug packaging applications might be expected to "migrate" into food or drugs to which it would come in contcict. Tremolite Kiarar.inn (nr- smrtinfti cn-na-ioe Basis Migration as used here is appropriate only in the sense of overall determination of loss of paper fiber, talc and other fillers tightly held in a hornoge leous sheet of paper. None of the types of paper commonly used for food contact applications has loose surface fibers or powdery material which will come loose on simple contact, hence the term "migration" as used in that sense does not apply. Mechanical action or "scuffing" of some sort is required to dislodge talc or other filler materials, and incidentally, cellulose paper fibers, from finished paper. With direction from FDA, a test method was devised which does scuff or abrade material from a paper sheet simulating the action a cylindrical tabic salt carton might receive during commercial shipment for an extended period of time. For simplicity, this is referred to as the Scuff Test in this report. A description of the directions from FDA for a test method is set forth in Exhibit I attached hereto. Paper Samples Ten samples of paper made for various food packaging applications were obtained from trade sources. Four of these were brown kraft, two with tremolitic talc and two wi.thout; four were white locker and counter papers, again two wffn (.runoiit.ic talc and two without; and two waxed papers purported to have talc. A more complete listing is given in Appendix I, Tables I and II. *!i.t,0 .,v,.J\-;i.p.&f.:rsci.'-c;' Ai?8 i,'Kt,l,jjyi,"t;!: -f J.li--,<Pfl Report h ^ ^ E 4 1 4 - 2 Page 2 Confirmation of Talc Content Since migration of tremolite from food packaging paper to food products in contact with such paper is the thrust of this study, pos.it.ive identification of the presence or absence cf tremolitic talc is important. Talc x^er se can be positively identified by both its characteristic X-ray diffraction (XRD) patterns and petrographic microscope examination. However, attempts to positively identify ti a talc in any of the caper samples as received proved unsuccessful by either of these methods; and, it was not until the paper samples ware low-te:iu:>ore . (400C) ashed that talc was detected and Identified by these methods. Both the Longview Paper Company and drown Company have advised us that their sole source of supply fc^. talc is Jonns-Manville. Both coiiranys ' purchases of talc are restricted to J-M "CYCLO-SORB", a grade of talc containing approximately five (51) percent tremolite by weight. The actual talc concentrations of the paper samples, as determined by X-ray diffraction, are located in Table II. Scuff Test The philosophy behind the "Scuff Test" was to attempt to simulate actual shipping and handling conditions of food-containing packages!. JLu ci is^ UldfrR.l U L iu U.U.X. OilJL / \J Cll. Li. Cu , 'Ll -L'/ i. ClJ. X O iiX p p iiltj / most, severe and prolonged shaking or vibr a o f the packages will be incurred. During this time, it is possible that the vibra ting contents could have an abrasive effect on their containers, thus possibly causing some of the package interior to be scuffed off and mixed with the contents. Therefore, a test that could simulate these conditions would permit examination of the material scuffed off and determination of what, if any, materials (i.e., cellulose, talc, tremolite, etc.) have been dislodged from the paper fiber. J-M was directed by FDA to use salt as the medium for the "Scuff Test" since its sharp edged cubic crystals would act as a more abrasive material than any other dry food substance or drug. (See Exhi}')it 1 Paoer containers were simulated b1 1 .nxng the inside of 8 ounce squat glass jars with test paper. Vibration settings on a shake tester were set at its maximum amplitude of 1/iG-inch ^'1/o-inch full excursion) and minimum frequency of 8 cycles x5Gr second. It was soon found though, that these condition did not produce any visible vibration of the salt. The contents singly rode up and down with the jars. It was not until the frequency was:, raised to approximately 15 cps that visible movement was in evidence. This: fact aroused some question as to how much, if any, prolonged shaking actually does occur to packaged foods during transport. It was calculated that a freightcar, having a flat spot on one pair of wheels, traveling at 40 mph would onh' vibrate with a frequency in the range of o.8-7.5 cps; ana at 60 wyn, 10.2-11.2 cps, depending on wheel a fume i.or . However, is was d.eia. d to run the initial Lest at severe enough eonditions to cause det.cctaole movement of the salt so that microscopic analysis of the salt would be meaningful.. However, one must recognno it is possible that the salt and glass jar were moving at tlit .-.nit frequencies which were not apparent to the eve, and it: i.. conceivable that the frequency rate of 10 cps nay more near 3y aupJ ic.xd:e vibration and possible scuffing during commercial shipment. if this is so, based on the delta frori the 10 cps test, no degradation would be anticipated under actual shipping conditions. A fourth test was then initiated to determine at what rate the scuffing occurred at the high'..:- frequency of 19 cps. Again, sample RS 7 3242-2 v s selected ifr -vation because of its performance in Tost 2. dimples were ruuc\. from the vibrator at 2, 4, 6, 12, 24, 43, and 72 h e w . Dupl icate samples were run for the 2, 4, and j-hou'" vests in order to rve as a cneck for the minute amount of residue w e t e d . It must be emphasized that these results only reflect the scuffing characteristics of this particular pape X iacVLt"03-.Ct and may nor be representative of the other papers. This sample demonstrated that the rate at which the integrity of the paper is broken dew/ is linearly related to time, up to 48 hours. The quantitative result' ire located in Appendix 31, Table IVA and a plot of the paper residue weight versus time is represented in Appendix III, Figure r . Mirrnqr'n n b .* .4- n ir^nh -in pynnn nah.inn of the residues revealed paper contained and so far as can be. determined optically, in the same proportions. This leads to the concise..on that, the material scuffed off and recovered as residue was due to the partial destruc tion of the integrity of the paper lining itself, and cannot be attributed simply to the migration of any select materials such as talc, cellulose, fillers, etc., out of the paper. This conclusion is supported by the fact that approximately the same amount of material was recovered from cuffed papers which did not contain tremolitic talc as those which did. Comments on Test Procedure Although only limited testing has thus far been performed, it is apparent that attempts to quantify test results at these exceeding]:/ low levels of concentration is difficult. It is equally difficult i-e generate reproduceable results. A case in point involves the use of technical grade salt which has a maximum insoluble impurities limit of 0.005 percent. In using 200 grams of salt, it in possible to have between 0-10 milligrams of unwanted impurities contaminate the residue deposit from each tost. When it is considered that, only a few milligrams of abraded residue is recovered at the conditons the test was run, it is obvious that a deviation or error of well over 3.00 -icrrarc is j *ssibl >_. b u r 3. a c it be emphasized that cl though v. ;ght. aii coronce v s io-n.d jn some samples run at identical co.x,iLiou:,, this h- . :- on the relative proportions of materials identified microscopically. -1,n.uL ff.y*.* ',....A..,..:..n.r..,1bfty.i y ReportHg. E414-2 1 , Page 5 co. 'LUCIONS Inspection of the results obtained from the Scuff Tests lead to the following conclusions: 1. At a frequency of 10 cps or a frequency equivalent to that of a freight train having a flat spot on its wheels traveling almost 60 mph, no evidence of paper breakdown was detectable when the samples were run for 24 hours, and no migration at all was detected. 2. As reported before, visible movement of the salt relative to the movement of the jar was not in evidence until approximately i6 cps. 3. Paper breakdown due to the abrasive action of the salt is detectable when run at a frequency of 19 cps and 1/8-inch full excursion for extended periods of time. But let it be emphasized that this frequency was settled upon only to ensure visible salt movement within the container, and at the time this frequency was selected, there was no reason to believe that such a high frequency rate was necessary to duplicate the vibration and move ment that actually occurs during the commercial shipment of food or drugs. It is, therefore, very possible that the frequency V--i4-/**. ^ -T 1 O r*v*\<r* rorul 4-Arl nn 4-r\c*4- i ! r\i o f a r m n r o q f r i ririArf- than those v?hich occur in actuality during commercial shipment. 4. In all cases, the material scuffed off and recovered as residue was due to the partial destruction of the paper lining itself, and is not due to the selective migration of individual materials such as cellulose, talc, tremolite, etc., out of the paper. Ihe examined residues were identified to contain all the materials of the original paper sample in the same proportions, as best as can be determined optically. 5. Although only limited testing has thus far been performed, it is apparent that attempts to quantify test results at these exceedingly low levels of concentration is difficult. It is equally difficult to generate reproduceable results. REC OMMENDATIONS It is recommended that: 1. A determination must be made as to whether the test conditions described herein do, in fact, duplicate conditions during actual commercial shipment of food and drugs.  i*. S * `fi P ...NfiJ.fIX ~ AlvU $!.& >2*afr**? f*. p -iq "* f fcf t"A ft Rqx^tNo. E414 -2 Page It is essential to perforin additional testing to determine if during commercial shipment of food and drugs, the vibration and movement encountered is sufficient to result in the partial breakdown of r.he paper packaging. This is necessary as the tests described herein indicate that there is no migration of tremolite or any of the ingredients of the paper unless there is a partial breakdown of the integrity of the paper itself. This test has not established whether paper breakdown actually occurs under commercial conditions. ntification No. RS 73242-1 RS 73242-2 RS 73242-3 RS 73242-4 RS 73242-5 RS 73242-6 % PS 73242-7 RS 73242-8 RS 73248-6 RS 73248-7 APPENDIX I Tabic 1 DESCRIPTION OF PAPER SAMPLES TESTED Source Description Longview Paper Company Brown kraft paper reportedly con taining 6.7-pound CYCLO-SORB per 1000-pound pulp. Longview Paper Company Ditto except containing 10.2-pound CYCLO-SCRB per 1000-pound pulp. Longview Paper Company Ditto except no talc. Brown Company 40-pound MG bleached bag stock coated with 5-pound clay latex, used for cookie bags. Talc conterr not stated. Brown Company 30-pound white DOK, wide food wrap use. Talc content not stated. Brown Company 25-pound Royal white waxing (this sample not waxed). Wide food contact uses (cookies, sugar, etc. Talc content not stated. Br Dwn Company 36 1/2-pound Spec, white locker waxed one side. ("Wax" not apparent) . Used for freezer lock.', paper. Talc content not stated. Longview Paper Company 30-pound No. 801 wrapping paper. No talc. Brown Company 31-pound Royal white food wrap pap> (waxed). Talc content not stated. Brown Company Printed and waxed paper for wrappi butter. Talc content not stated. nui fcluv*. 'f f l TP**#"5f~F% ADO EhSixbn.iiiS Cfc^ics TT-v h JL^f Report N ^ e 4 1 4_ 2 Page g APPENDIX I Table II TALC IDENTIFICATION OF PAPER SAMPLES BY X-IAY DETERMINATION* Sample Source Reported Talc Content % Talc Determined By X-Ray Diffraction RS 73242-1 0.67 percent 0.35% RS 73242-2 RS 73242-3 1.02 percent None 1.0 % ** RS 73242-4 RS 73242-5 Unknown Unknown ' 0.05% ** RS 73242-6 1-1.5 percent 0.60% RS 73242-7 no TOT/IO-Q 1-1.5 percent TCT/-\r>a 0.25% tr RS 73248-6 RS 73248-7 Unknown Unknown ** ** * Pacer was ashed for X-ray determination. ** Below detectable limits tfj**.v?<**.-rU*t. '* i iAUti*iii,I.Lin *' >*<*if llil I"**l.? i<* ft 3*?>f .U RcoorU/'O. E 4 1 4 - 2 Jajc 9 APPENDIX I Table IIIA QUANTITATIVE RESULTS OF SCUFF TEST RUN AT 19 CPS - 24 HOURS Residue Due To Scuffed Sample_______ Paper (cjins) i RS 7 3 2 4 2 -1 0 .0 0 1 5 1 RS 7 3 2 4 2 -2 0 .0 0 4 4 4 RS 7 3 2 4 2 -3 0 .0 0 1 4 8 RS 7 3 2 4 2 -4 0 .0 0 3 5 6 RS 7 3 2 4 2 -5 0 .0 0 1 3 3 RS 7 3 2 4 2 -6 0 .0 0 3 5 3 RS 7 3 2 4 2 -7 0 .0 0 5 0 8 RS 7 3 2 4 2 - 8 0 .0 0 2 9 3 RS 7 3 2 4 8 -6 0 .0 0 6 8 5 RS 7 3 2 4 2 -7 0 .0 0 7 9 8 Loss per sq in Loss per sq cm of Paper of Paper (gms/sq in)________ (gms/sq cm) SOi--1 J . 83 X 1.28 X 10" 5 2.44 X 10-4 3.78 X 1 0 "5 0.81 X 10-4 1.26 X 10-5 1.95 X 10~4 3 . 0 3 X 1 0 "'5 0.73 X IQ "4 1.94 X 1 0 "4 1 .1 3 3 .0 1 X 10-5 X 1 0 - 5D 2.79 X i o - 4 1 .6 1 X 10 : 4 .3 2 2 .4 8 X 10" 5 r~ X 10 ~ 3.76 X ! 0 " 4 5 .8 2 X 10 5 4 . 3 8 X 1 0 " 4 6.79 X 1 0 "5 Report No. 1X 14-2 APPIN'-D.iJ Table T1B APPROXIMATE NUMBER OF TALC PARTICLES PER 35 MM DIAMETER RESIDUE 01; N.JL2X ORE MEMBRANE BY PETROGRAPHY ____ AT 50OX - RESIDUES EROM 19 CPS - 24 HOUR TEST Actual Talc Content Number of Number of Number of __ of Paper________ Talc Particles Chrysotile Fibers Tremolite Tiber 3242-1 5242-2 3242-3 C .35% l.C % kk 29,000 2 . 52 ,r00 2 2,500 0 0 0 668 2,002 0 _2-12-4 '242-5 0 .05% >r5V 7,500 3 Present 0 0 668 0 2 '.2-6 3242-7 3242-8 70/ft_^ 1 T 3248-7 'L 0.60% 0.25% x* X7T A* 35,000 50,000 10,000 t o o w a x v n o rea u Too waxy to read 0 0 0 - - 2,804 2 ,937 Vr\ - -.U!OW det>ci.able limits. Predominant constituent appears to be minute blebs of crystalline wax range n<j from 0.5 to 5 microns in size. Very small percentage of carbonate and cellulcse-tvpe fiber. tie average size of these talc platelets is approximately 1 micron x 1 micron 1/2 micron. Using this average particle size and a density of 2.8 gms/citr' a.or ta.lc, 29,000 particles would weigh approxinaudy 2 x 10"Dmg, and 52,500 'elides would weigh approximately 3.7 x 10"Dxag. .-refuse amount of doubly terminated minute acicular crystals (2 to 10 microns in j.e.rgth) which are anisotropic, but unidentified. These acicular crystals n r not retained after ashing. L.1 nks wo re examined to try to establish background level of talc. CELITE l> 43-7 (-all t-washed water) was studied in some detail by employing 20 fields 1 > at 50GX. Minute particles of carbonate-like material predominate and may uto as much as one million particles per 35 mm diameter residue. Certain ' s of talc platelets were detected on these blanks for no discernible possibly duo to contamination. Tiro calculated results for the x No. of talc particles 3,000 (platelets, few shr.x No. of chrysotile fibers 0' No. of tremolite fibers 0 <ollulose-liko fibers trace jANODHSEsH-ri&xuEm^Li IiEOrCeEsil fef lcr i I!i\ K - < > Report N o. E 414 - 2 P a g e 11 Time 2 hours 4 hours 6 hours 12 hours 24 hours 48 hours 72 hours APPENDIX I Table IVA SCUFF RATE OF SAMPLE RS 73242-2 (Determined Over a Cycle of 72 Hours) Total Average Insoluble Residue Due Filter Residue______ Salt Residue**_______ to Paper Abrasion 0.00236 gms * 0.00216 gms 0.00020 gms 0.00242 gms * 0.00216 gms 0.00026 gms 0.00445 gms * 0.00216- gms 0.00229 gms 0.00266 gms 0.00216 gms 0.0005 gms 0.00300 gms 0.00216 gms 0.00084 gms 0.00359 gms 0.00216 gms 0.00143 gms 0.00364 gms 0.00216 gms 0.00148 gms Average residue ** A v e r a g e from 7 salt blanks *J>y:ikfc& 'i. vr*u,sSL #F!1 ir^rv^; a*-.*JS ViltJ 8l'.s Rcpor^^. E414-2 Page 12 APPENDIX I Table IVB C E L IiU I.O S E A N D T A L C O N M IL L IP O R E F R O M 1 9 C P S F R E Q U E N C Y S E R IE S R S 7 3 2 4 2 - 2 BRO W N P A P E R Time 0 - Salt Blank 2 hours 4 hours 6 hours 12 hours 24 hours ~ - . 'V.J- 72 hours Estimated No. of Cellulose 7ibers Per Mc~' ane 400 600 1,100 2,500 >3,000-*>3,000-*- fuuu >3,000-*- Estimated No. of Talc Particles Per Membrane 70012 2,0002 5,0002 12, OQO2 17,0003 38,0003 68,000- 75,0003 1. The cellulose fiber population was tremendous on these membranes Their inter-twining and matting made counting extremely difficult. By extrapolating, their count could easily reach as high as 20,000 per membrane. V. E. Wolkodoff 2. Based on ash 3. Based on dissolved millipore membrane JO!nS-?.LLE t H m El3EE3luS CI 'Si-J S *.j T|~N RcnortNo- E 4 1 4 - 2 Page 13 APPENDIX II SCUFF TEST A. Equipment 1. L.A.B. type RVH vibration test stand or equivalent. 2. Millipore filtration apparatus, 0.45 and 0.80 micron filters (vacuum filtrati 3n' . 3. Fisher Magnetic Stirrer. 4. 8 ounce flint class, squat form wide mouth bottles. 5. Several 1500 ml l-akers (carefully cleaned). 6. Mettler Balance or equivalent. B. Reagents 1. Distilled water 2. Sodium chloride, CP 3. Test paper C. Test Method _-_ -- W MW ** o r O V/J. VW Vf JL. ..Li, 'm* i. * *. 8 1/2-inch. Curl the paper and place it inside a clean, dirt and fiber free 1/2 pint jar. Line the paper on the inside surface (there will be a slight overlap) ; mark this overlap with a few pencil dots? remove the paper and tape the outside of the overlap; then re-irsort inside the jar. 2. Weigh out 200 gm of the salt and place it in the lined jar. Cap the jar.' 3. Place on vibrator which has been set to run at 19 cps, 1/16-inch amplitude, (1/8-inch full excursion), for 24 hours. 4. After 24 hours of running, remove jar(s) from vibrator. Any run should also be accompanied by a control blank of a jar simply filled with 200 gms of salt. 5. Filter some distilled water through 0.45 micron millipore filters. Approximately 1500 ml will be needed for each sample. Also, use this filtered water to rinse out all containers and equipment with which the sample liquid will come in contact. It is important to keep all equipment dust and fiber free. .t!ius-r.m:ri!LiE n s r . # i s a E s oe ::; :.,.j iU 4.IC ? S> 1 f-^ X Page 14 SCUFF TEST (Cont'd) Empty the salt from the test jars into 900 ml (0.45 micron filtered) of water which is being itirred by a magnetic stirrer. Remove the test paper lining and tap it over the beaker in order to remove any salt inging to Lt. Then use an additional 100 ml of filtered " the jar and cap. Pour this into the beaker also, Allow the mixture to stir approximately 5 minutes in or ir to dissolve all the salt. Preweigh two 0 micron millipors fil rs for each sample, When the salt dissolved, pour the j.i.quia through the filter apparatus in 1 :h both filters are pre s=ent, one directly on top of the oth: , (the bottom filter is a control). Use an additional 2Go : of filtered water to rinse out the beaker and pour this ;.xrough the filter. (A w:tsh bottle provides the most effeo ..ive method of rinsing, ) Then use an additional 3C0 ml of fil ;.ered water to wash the f;.Iters. This will help wash away any sr.inute salt particles t.le*, i: are clinging to the filters. When washing is completed, X B 1; both filters dry --N- ~-- -_______~i _J___T-- 8. When the filters are dry, weigh them, T'ionci >amples are now available for microscopic examinetion. D. Calculations 1. (For 1 Sample) Filter No. 1 (Bfore) Filter No. 1 (After) X eras X (residue) qms TResTdue) gms Filter No. 1A (Before Filter No. 1A (After) Y gms Y A Z gnu (Z) gms Filter No. 1A acts as a control. It might change in weight by the amount of (Z) gms. This might very well be an increase in weight if all the salt was not washed out of the filters. But whatever weight is found in No. 1A, it must be subtracted from the apparent residue weight, because approximately the same change in weight will occur to the top filter as did to the control filter. 2 . (Residue) gms ( Z) gms = Actual Residue (gms) _ --J Q K S S r " K . L E H E f E * # Aslli ,*4.* ie?--ii - t j ^ RReco uo iot itEE441144--22 Page 15 3. The actual residue contains both the residue from the paper and the salt, so the actual weight of paper scuffed off equals: [Actual Residue (gins) ] - [Actual Residue (gins) from Salt Blank] = Weight of Scuffed Material % ' ti'< ; uIOpl^rI-I'1ro -s^ nI\vnlKnV.^- E X H IB IT 1 r] r*f'V ta St n vu 'W' M . ,v*. ?* Se-ty `v -J" i a! 'r V r . r*"f J'^ '-y 's.'' it M J 4 u '-w* V a f Tu R. S . Lamar - R&D Ctr Fiom' V. E. Wolkodoff - R&D Ctr Date. Augus t Copier.. Subject: FILL CR i'iIGRATION FF.OM F'~'TD WRAP PAPERS On cf CL'.:i oOoOF aY,,\,iAnuWcraussth in2g8 1973, I spoke to Mr. G. Higgenbottom jit, D.C. lie and Mr. A. Spiher had disc u,,. cr[ pos siole me lods which could be used to determine the am.jU;-1 of fille r :migration from a food wrap paper to tho ,TOod c; uff conta in,ed therein. It is necessary to devise a su itc_;j1iV*io method, sinee there is no standard method in axis tono>? Ihe lack :of an approved method was determined by Mr . A . i:oit:::, Pa,ck iging Chemist for the FDA. The method they sUC ge et is as fo 1. Co } tract a sma 11 container from the paper in question dau Udxxxdiiv 1111 wimi u r a n i c .v sait weiun . we acrreeu tnat reagent grade salt would used since it would not contain the insoluble additive: normally used in table salt. , Shake cr tumble the salt-filled container for 24 hours The intensity of shaking was not specified, but they will accept anything we feel is reasonable. 3. Remove the salt from the container and dissolve in a suitable quantity of water. 4. Filter the salt solution through a Millipore membrane (0.8 um pore diameter), and examine for "asoestos" fibers by the normal (NIOSII) methods. In addition to the above, the FDA would also like to have a determination of the limit of detection. This would be de termined by adding known increments of "asbestos1' or "asbestos containing talc to salt and following the same analytical procedure. Jv/' < ' l(. S^a///T--/` V . C . v.'o l k o d o f f jmw Si;a-.JiV L-*ili*T**"*, ,-f'c.iiij.rC*t-:1 X c p o t Nt>. E 4 1 4 - G Date December 12, 197 3 LACK OF FOOD CONTAMINATION LV CONTACT WITH PAPER DUE TO SHIPPING SUMMARY The purpose of this study was first, to determine the severity of the effects of transportation on the contents of food and drug packages and second, no determine the relevance of using an arti ficial tear to simulate the effects of actual shipping conditions. Specifically, the stud,' was to determine whether actual shipping would cause sufficient ibrasion to the containers to cause migra tion of part of the paper into the contents of food packages. Tnis study establish h, shat tremolite contained in talc used in food paper packaging . not migrate to any food substances during normal commercial sum ant and handling. Test containers of sal.* uined with tremolitic talc-containing paper shipped by truck fro::, eonver to New Jersey and back caused no break down in t) a integnt" ;f the paper and no migration of the tremolite or any otter ingredient of the paper. Additionally, food packaged in tremolitic talc-containing paper purchased at a local supermarket showed no evidence of tremolite migration due to paper breakdown, mu -r-. rt-.r- -^ ,t ^v* t.to-re* or- T*7ViTr*h \\7 brp 1i*Vp Iv +o & U J - U e i L , P , J u . U ' i i ' . j L , X CO P U L . C O Cilit-l '/C L V . '. - i . j c. v * yv.. v v. - < It was established by the data reported rn Report No. E414-2 that migration or tremolite from food packaging paper to food can only occur if some on.-urnl breakdown of the piper occurs. Migration does not occur unless the integrity of the paper is at least partially destroyed and then all of the components of the paper will migrate (be released) in the same proportion as they exist in the paper (no selee c.b/o migration). This conclusion was verified by the "Scar*: Test" reported in Report No. E414-2, which was questioned as possibly being more severe than actual commercial shipping conditions. This present, report establishes that the conditions established in the "Scuff Test" are indeed much more severe than actual commercial shipping conditions. Actual shipping conditions result in no migration, at least to reliable levels of Identification by trans mission electron microscopy, optical (petrographic) microscopy, and weight determinations. Contents Summary, Discussion, Conclusions, Recommendations, and ^Appendix. Reported by fl y, Za/.enski Reported by Rf B'-lj t* fevlJf"'...-iiit f j,1J >1! I'J('.fc :J* tr-.rbn.,i,j' ! iy ReportNo. l'ase K414-6 1 DISC -c: ON Introduction Initial studies on tremolite migration from paper manufactured with tremolitic talc established that migration will only occur with partial destruction of che integrity of the paper which is in con tact with the food. V iithout some destruction of the paper, no measurable migration occurs, i.e., there is no selective migration initiated by the abnormally severe '`shaking" or "scuffing" of the packages' contents. To simulate this action, an artificial "Scuff Test" was employed which deliberately caused paper destruction. This enabled us to analyze the mechanism of migration. The purpose of the present study was to determine the relevance of .this artificial test to actual shipping conditions, as well as evaluate the severity of actual transportation. To accomplish this, specially prepared containers were sent by REA truck from Denver to Manville, New Jersey and back to Denver, a round trip of approxi mately 72 hours and 1.000 miles of constant truck travel. In addition, actual f:ood coiamodivies were purchased at a supermarket for the purpose of analyzing them for possible tremolite migration. Actually Shipped "Control 1-'f" Samples Four paper lined, salt containing jars were sent by truck on their 77-hour journey. These lined jars were prepared in identical fashion to the test jars used in the artificial "Scuff Test".- Four 'different test papers v/ere employed, each specifically chosen because it concerned tremolitic talc (they ranged from 0.25-1.0 percent talc) . Two hundred grams of technical, grade salt served as the food medium in each of the lined jars. Evaluation of the salt samples after shipment consisted of: (1) determining the weignt of the abraded material from the paper, if any, (2) in spection for cellulose fibers, taLc, tremolite, and chrysotile, by petrographic analysis, and (3) inspection for talc and asbestiform materials by Transmission Electron Microscopy (TEM). These analyses wore conducted in the same fashion as were the samples that were tested by the artificial "Scuff Test" reported in Report No. E414-2, with the exception of additional, analyses by TEM m the present test after no migration was detected by petrographic analysis. In examining these samples, an effort was made to concentrate on the detection of +-ho presence of talc since the previous studies showed no selective migration. Therefore, it can be presumed that if no talc is detected in the residue, then there would be no tremolite (on a vo/ghf basis, there should be 95 unit weights of t.aic for evoi y 1 .nil. w n i b u n o: tremolite m this particular talc). This tochu.: u s e was nsuc: a s conservative means of (.j.Mip ;!i^ re"*, h.i*'.?'". .- ' L\f..t* **#.*r,.. t *'.*v. ;*"?/--'f#'*;'h*J>IL'i=*fcv*^/S R e p o r ta je . Page E414-6 2 detecting the presence or absence of tremolite. To serve as check, thorough scanning was mada for tremolite, even though its presence might be beyond the levels of detection with practically insignif icant amounts of paper breakdown. The overall analyses indicated that no migration was found. Thus, the actual shipping route of 72 hours of constant road travel did not create conditions severe enough to cause appreciable destruc tion of the paper liners. Petrographic analysis of all four test samples revealed only a yossib`o trace of talc and no evidence of the v'-asc-nce of any enryso ".e or tremolite fibers due to migration. Upon comcar ing these results to the artificial "Scuff Test" that was run for only 24 hours, it is evident that the artificial testcauses concisions which are overwhelmingly more severe than actual commercial transportation. As an example, the results of one particular paper sample that was run in both the artificial and no fun ]. tests are compared in this tabulation. Coaparison of Artificial and Actual Shipping Test Results Ptrographie Evaluation wanner or Number of Talc Chrysotile Particles_____ Fibers Numoer or Tremolite Fibers Duration Arcj1icial Test 52,500 0 2,002 24 hours Actual Test possible trace not detected not detected 72 sk urn m addition to examining the shipped salt samples by petrographic methods, they were also examined by TEM ( I 'OOj X) . The fields 'mere selected at random after considerable scanning specifically lookincr ror tele and tremolite. Thirteen plates were mace in thos'e cases vy-0;L'e scanning indicated the possible presence of talc of tremolite. The results from examination of these 13 plates showed the possibility of only one talc particle and also the possibility of only one tremolite fiber. In addition, no fibers of any kind longcr""than 5 microns could be detected. Tables 1 and 2 in the Append;: have the complete examination results in tabular form. This complote and thorough analysis of these shipped samples establishes that normal transportation does not create a severe enough environment to even allow salt (which is one of the most abrasive food materials packaged) to cause appreciable des tracti jn of its containers. Thus, under actual commercial conditi us , mi oration oi from] itic talc caused bv pan or breakdown du to umppmc m tail nigiily unlikeiv E.414-6 3 Evaluation of Food Products Five food items were purchased at a local supermarket for the ^ purpose of anaiyzing them for the presence of tremolitic talc in the paper packaging and the possibility of any migration from those papers. Items that had been transported the longest distances as well as those foods that would be particularly abrasive were specifically chosen. The food items selected were macaroni, rice, salt, corn rlakes, and dry, non-fat milk. The petrographic analysis of those food items indicated absolutely no migration of tremolite fibers. The food containers were analyzed by X-ray diffraction, and petrographic methods to identify if the paper packaging contained talc and tremolite. Table 3 reports the results of these analyses. Petrographic examination revealed no talc in four of the five contents, with only rhe possibility of a trace in the Morton's Sait. Examination of the Morton's Salt was extremely difficult because one of its additives, sodium silico aluminate (a crystalline material sti.il present after ashing), interfered with the optical examination. Subsequent examination showed no tremoiite or chrysotile fibers present in any of these foods. These results are located in Table 4 in the Arroendix. TEM examination of the ashed food samples also revealed no tremolite fibers. Several small chrysotile and talc particles were detected, but all were sub-optical in size. Each ashed food item underwent a thorough examination of at least 20 fields by the TEM, each field 80 microns sex are. Tnese results are located in Table 5. CONCLUSIONS 1. Analysis of salt test samples which endured approximately 3 days of constant road travel shox'/ed no evidence of appreciable breakdown"Tn the integrity of the paper liners and no migration of tremolite fibers, although the test papers were known to contain tremolitic talc in the range of 0.25 to 1.0 percent. 2. Analysis of actual food commodities purchased at a supermarket also showed no evidence of appreciable breakdown In the integrity of the packaging paper and absolutely no migration of tremolite fibers, even though three of the paper containers were Known to contain tremolitic talc. 3. These studies support the conclusion arrived at in Report No. E414-2: Regardless of the composition of the paper (container), migration will not occur unless severe enough conditions cause the container's conter, tr. c scuff arid abrade the inside lining enough to c a m e paper or <ckdovr . o. E414-6 Page 4 4. It seems evident that actual conditions of transportation do not create a severe enough environment for paper breakdown to occur; thus, migration from papex is highly unlikely. 5. The artificial Scuff Test, as used i i Report No. E414-2, was found to be appreciably more severe chan actual commercial shipping conditions. RECOMMENDATIONS It is recommended that an artificial Scuff Test should not be used to simulate actual transportation for food packaging migration studies because it produces results not comparable to actual commercial shipment. ,J*M E H3 rin?u*f* RTPir^i?i*v r$rb.*ft>l Repo^po. E4 1 4 -6 P?ge 5 APPENDIX Table 1 RESULTS OF PETROGRAPHIC EXAMINATION OF RESIDUES FROM SHIPPED TEST SAMPLES5 Samole No. RS 73242-1 RS 73242-2 RS 73242-6 RS 73242-7 Actual Talc Content, of Paper1 (percent) 0.35% 1.0 % 0,60% 0.25% Talc Particles Per Membrane^ possible trace possible trace possible trace possible trace Chrysotile Per Membrane not detected not detected not detected not detected Tremolite Per Membrane possible trace not detected not detected not detected I III *1 _ ^ ^ _ 1 ____ _i_ -3 -- J_ ^ . --- 2 -A J k \T M MV* -3 . J-* . ' **\ 4-- * /*% >-- 2. The entire contents of the test samples were dissolved in filtered water and filtered through a 0.8 micron membrane. Therefore, only insoluble impurities present in the contents were collected on the membrane. 3. Three fibers present ranging in length from 300 to 480 microns, but have to be considered as outside contamination, as talc is commercially ground so fine as to prohibit the presence of chrysotile fibers of such a length. 4. Based on the total examination of one 10 mm field, only one tremolite fiber was detected. This could have resulted from contamination from unknown source. 5. These analyses were based on the examination of at least 100 fields of view per sample at 500X magnification. Possible Trace should be divided into 2 terms: Possible - optical properties indicate the presence of a particulate mineral, possibly talc. Trace - if there, the above is present in a trace amount. J0HHS-M3Viix xW Ane e[:3:ee::;s sesto it Reprcx ^ ^ jli Page E414-6 6 APPENDIX Table 2 EXAMINATION 0? SHIPPED TEST SAMPLE RESIDUES BY TRANSMISSION ELECTRON MICROSCOPY____1234 Sample No. RS 73242-1 RS 73242-2 RS 73242-6 R.Q 7XVJV-'/ 8000X - TEM Plate Number 2216A 2216B 2216C 2216 D 2217A 2217B 2217C 22.18A 221SB 2218C a 2219B 2219C Talc Tremolite 0 None 0 None 0 None 0 None 0 None 0 1 possible, 5 micron long 0 None 0 0 possibly 1 None None None a None 0 None 0 None 1. Samples ashel at 8Q0.< for .16 hours. 2. Entire samples were scanned looking specifically for talc and tremolite. 3. Fields were selected at random. 4. No fibers of any kind detected longer than 5 microns. Examination performed by V. E. Wolkodoff jeiOS^wMiE lcoFA? EUSIBEEtftS center H Report Page E 4 1 4 -6 APPENDIX Table 3 PETROGRAPHIC EXAMINATION OF ASHED FOOD CONTAINERS Optical Examination rcr Chrysotile and Tremolite at 50QX Sample 4385-35-1 4385-35-2 1a h~/\ Wr\ vr- w->/--r/~ a * 4385-35-5 4385-35-8 Chrysotile ND ND ND ND Tremolite present ND >TT> present present A PPENDIX r.ible 4 ASHED FOOD MATERIALS :EXAMINED PETROGRAPHICALLY _ _ _ _ _ FOR TALC AND BESTIFORM MINERALS Commodity 7 Talc in % of Total Package Pr i ;ence of Container Contents Examinea Tremolit5 in Container^ Talc Detected in Food Contents Tremolite and Chrysolile in Food Contents Macaroni 0.23% 31.677 Positively Identified Not Detected Not Detected Dry non-fat milk 0 . 8 2 % 23.lb% Not Detected Results Inconclusive Not Detected Quick Rice 0.2%,% 10.777 Not Detected Not Detected Not Detected Corn .Flakes i'.or^.,1. s Oalt12 0.05$ 1 .26? 6.kl% 13.557 PositiveLy Identified Positively Identified Not Detected Possible Trace Not Detected Not Detected 1. 85 g dissolved on millipore membrane before ashing. 2. Examined by petrographic analysis. Conclusions based on at least 100 fields of view. NOTE : All food materials ashed at 800F in air atmospher; for 7 days. To remove all carbonaceous material, O--V/~">Q--.TtO-14" /O"V* i. xwx v^i.A o o<~d'oxT4o-) d**> Tliihx giTVuiqc -ly% ^oAcwm p ci*as+o*u-yiac m/a>jr ^,>,-cs: r c ^ u,.Ji r-v*c Q.Q. j tut opbical properties vouj-d change. Comments from Petrographer: The ash from dry milk was exsnemely difficult to read and the results are inconclusive. An extremely snail amount of the crystalline materials in ashed Morton's Salt has been dentified as talc and the percentage is officially listed as a possible trace. Examination performed by V. E. Wolkodoff. Ar ?INBIX 1 a''le 5 TRA.;21ilSGI 01' ELECTRON IXICROSIOPY EXAMIi;ATTON OF F100D CONIENDS (\;d!E0) r;r'> ''' Description % of Total Package Contents Examined TEM Finte R'o. Macaroni Ash 31.67% --------------------1____________ . h 3 i 5 - 3 5 - 2 F Dry Milk Ash 23.l k % 2 ? A B C 2 \\ 5A B C Talc ND ND ND ND ND ND Chi-ysotile 2 <1 micron ND ND H1TiTnp)^6 -f O. ND ND Au . ND ND ND IIL' ND ND U5^-3>-UF Ashed Rice 10.77% 2 7 6a B C ND 2, one > 1 micron ND '1 clump 2 particles .1< 1 micron ND ND ND ^365-55-5F Ashed Corn Flakes 6 ,\l% ^35-35-8F Morton Salt Ash 13.55% 2217A B C 2238A B C ND ND ND 1 particle 1 particle ND ND ND ND ND ND ND ND ND ND ND ND ND y. . . . . ! # if , / r `, .. '-.''.C-- J_-.A , xA '- f\X' ; 4 -. _yctl^ L /J orican industrial Hygiene Annodi ation Journal iy 1rJV3 Codo. No. ' i n d u s liia l H ygiene S um m ary Reports 37 5C UC 72 8'C CONTRAI, CANAC Viir-v J o u r n a l b rie f in m m c u is tfc r o c d fr o m <LnI\ ;H .(K itK s H li k h m u y be u s e f u l i r * u l l t r m e m b e r s #i bue p i > l \ v s m n . \ J t l n \ s y o u r c o m m u n i o j t i o n s t o t R it i . irti b \ S tiu rt> c i;:e r. f R v l I l t a m i S .itc t) 1 ^u u . i t e r ) , U m ilim i; .520, K o d a k U a /k W o r k s , K .e .t m .m K o d a k C u n i j U i i ) , K ih h o s ie r , .New \ o r k 140 50. Asbestos, Tale and Nirics in Relation to Gastric Cancer Rccenth. .Meriii' suggested char the high incidence of gastric caneer in Japan may be associated with treatment of rice with talc in Japan. He noted that some commercial " laics" contain asbestos. which he proposed as an ctiologic agent in gastric cancer. Mer i:" <-n.m a rcDoil ui u ,,...:.!! of gastric cancer in a group of mstiiaucn v.uir - ers exposed to dusts containing asbestos and a larger excess of pui non.try carcinomas and pleural mesotheliomas m miners who appear to have had nine I exposures to as bestos and talc. He not d that some geo logic deposits of talc at; associated with tremolite, anthopin iiite and clm sotile varieties of asbestos, accounting for the presence of fibrous particles of asbestos to gether with piaty particles o! talc in some commercial preparations of " talc."' Our group lias carried out tests for car cinogenicity of various preparations of as bestos through experiments with animals. The picsent paper summarizes some results and reports a new experiment with a prep aration of talc containing asbestos. A pos sible alternative mechanism mvolvint; ni trites in gastric carcinogenesis .s discussed. In 45 hamsters maintained throughout their lives on diets contain.ng I'm of the ch;yr.otile or amoshe \ur\. . s s,f ;tos. we iotmd no gastric carcinomas and nu la- *ll,U v-pri. vij L(. front nd ui'd rdiMiT.Km. ' `ip.'Mftvd by U S P M S R e s o ry ii O rarti i i is ii u r .v < J O c s f-i t h in d *> Wvl y Hy y G um { o f.r.c . Rippel mors in the gastrointestinal truel except lor a ncoplam in the mesentery of the colon.J We are unable to relate that lesion to the treatment, since ashing has revealed no as bestos fibers in it. After intrapleural injection of 25 mg chrysolite or umosite into hamsters, wc rc . rc .i'iK.noseu as pieuiui m. .Ah,. liornas.-' Eight to 10 such tumors were found in each of 3 groups of 50 hamsters treated at this dose level.1 We have now completed an experiment in which the hamster-intrapleural method was used to test for carcinogenicity of a sample of talc containing asbestos. For this work, we obtained samples of .ommcrcu! talcs from Whittaker, Clark wnmek. Inc.. New York City. A sample of cosmetic taicum powder grade was seen by microscopic ex amination to be competed of piaty particles typical of the mineral, talc (hydrous mag nesium silicate) Another ample of a grade used for some indust-ial purposes ("-13 Talc" ) was found to he a mixture of piaty and fibrous particles. X-ray diffraction analysis revealed the presence of major amounts of tremolite asbestos and talc and a minor amount o a serpentn-' mineral fantigorite). Each of 50 hamsters were raven right mtiaj.-leurai injection m 25 mg of tins snrng'e sus; i'm'cd in .5 : il sr.nnc. The animals were followed for their iue spans. No tu mors attributable to the treatment were found. Granulomatous lesions were com- fi I> ! 1 t i 228 mon on plcqra! surfaces, but these lesions tended to be small and focal in contrast to larger and more fibrotic lesions induced in hamsters by chrssonic or amosite. The negative results of tins test for car cinogenicity of a talc containing asbestos, and our earlier test on feeding asnestos to hamsters, do not offer support to view that asbestos-containing talc contrsoutes to the incidence of gastiic cancer in Jaauri. Although death rates reporters u,. ramie cancer arc notably high in Jap...', m com parison to other countries, the h.ai-.e t re ported rate conies from Chile.* S . ues ot gastric cancer m Chile have been tenoned from our laboratory with an n\po:re:us that high rates for esophageal and g istr.e cancer may be due to conversion ot nitrates to nitrites by soil bacteria with subsequent syiiuu.C;> c f ..it. eer.'.T.e in plants used as food or mrougn ;mu auiuii in the stomach with secondary amines in ( o o d .'J Chile has the world's largest known ge ologic deposits of nitrates, 'much arc used as fertilizers. Nitrosamine lias been reported in wheat plants and wheat grains.1' Nitro- sarnmes can form through interaction of nitrites with secondary or tertiary amines in the siumach, and have been shown to induce esophageal and gastric cancers in rats.;-H High concentrations of secondary amines have been reported from Japan in dried [i\h. The situation invites attention to a po tential role of the n.trogen cycle m environ mental carcinogenesis. A source for direct ingestion of nitrites by human populations May. 973 arises from use of nitrites as food additives. Ollier potential factors in gastric carcino genesis have br cn recently reviewed by Haenszcl c t a/.1" who found no support for the talc-asbestos hypothesis on epidemiologic grounds. 1. Mcrltss, P,. R.: Tide-Treated Rice .md Japanese Stomach Cancer. S ; w n i ' /7J.T141 (Sept. 17, 1971). 2. Smith, VV. E . L . M iiic r , R. EKasscr and D. Hubert: Tests fot Curcintvjcmctty o f Asbestos. A n n . N e ic Y o r k A r m i . .S'c reric* 1 3 2 : 4 56 (Dec. 31. 1965). 3. Smith. VV. E . D. Hubert, and M. !!ado!!et: Biologic Differences in Response lo [.one anti Short Asbestos hibers .-I m cr I m l I I lime. J . 3 3 : Abstract --162 (Feb. 117 2) 4 . Macdonald. H.. and P. W olf: in F . p u l a n i o l o p i f i l l . I . s p a i n i c i t ' n l uia,1 C o n n til S i u i i ` i' 1 o n O n l i n e C u m e r , Japanese Cancer Assn. G A N N Monograph 3 II96X). 5. Zald iv .ir. R.: Geographic Pathology o f Or;d. Esophageal. Gastric and lntesun.il Cancer in v , 25:1 (1970). n. n e u ie i. aid ........-- J"- V o rk o m m e n von Niiros.inuncn in N . i'm in cs- unJ FU 11c r m iUe i n . A< n m \ n - S c f n n t c d c l ' n v * A r c h . P h a m . i-v/i. P a t h 2 5 U 176 f 19 AM). 7. Sander, j. . F. Sehw emsherg. and H. Mcnz: Untersuehi'ueen uehcr die Fnisk-hunc cancerogener N i ' r >sanunc. im 5 I n v e n . l i o r p c - S c v i a ' i ' / . l u l l , p l r . s it, C h a n . .I49;H>91 (I96X ). 8. Drw cktcy. F .. S. Iv a n fo v ic . and D. Schmacii!: Organotrope careinoecne W irhunccn bet 65 versehiedenen N -m tro s o A ermnduneen an UD- Rallell. /.Inh. K n h i j t m i h . 7/v 1()} i i 9 A7 >. 9. Kavvamura. 1., K, Sakai, and F. Miyaz.twa: Studies on nitrosannnes in foods (IV). Dis tribution of v'condatv amines n foods. /. l o u d H y p . S o c . ( J u r a / : ) 1 2 . 1v 2 ( 1 9 7 1 10. Haenszel. W., \ [ . Kun h.ira , M. Sept, and R. Lee: Stomach Cance- antoni; Japanese in Hawaii. J . S a t ' l C a n o e ,- I n n . 49 96y (1972). IVd(win: E . Sm ith . M .O . Health Research Inuiiiue "ttirlcigh D i< k m u n i U niversity M adison, N J . 07940 ' /t`A*i T O* :<jo on O S OcaJC***. LteXitetateal* iteA la1 i I d.V ui j c: w/. V. .'iC.';rc;osy excapo sor raro ::'.::^:. 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