Document jgxBxJZoVnwqNm3wO6Nn1yLa5

HEALTH STUDY OF ITALIAN TALCS WHITTAKER, CLARK & D 4N IE L S, IN C I0C0 COOL1DGE STREET SOUrm PLAINFIELD, N J. 07080 U.SA . TEL: 201-561-6100 PLAINTIFFS EXHIBIT WCD-202 LoGiudice/WCD/0323 PREFACE For several years the scientific community has been gathering data and preparing numerous studies in an effort to bring fac ts to the public in lieu of incomplete and, in far too many cases, inaccurate allegations of supposed hazards to which the public may be exposed T he report which follows was undertaken by the Department of Occupational Medicine of the Univeisity of Turin under the direction of Dr. G.F. Rubino, an internationally recognized epidemologist. It was presented tc the American Industrial Health Conference in San Francisco on April 15,1975. The study was conducted on 1794 mineis and millers who worked in the talc mines and milk of Pinerola in Northern Italy. (These mines are the source of the Italian Talc which is used exten sively throughout the world arid has become the world standard of quality). The study is unique in that the Pinerola region is the only talc producing area in the world where its miners and mil lers have remained stationary and, for the most part, been involved in talc operations only. This tradition provides a valuable opportunity to study a large group of people exposed over many decades to levels of talc far in excess of that to which any consumer could conceivably be exposed. This experimental design is thoroughly comprehensive and statistically conclusive. It should be noted that the Italian Talc is of cosnetic quality due to its purity. The report re assures the cosmetic manufact arer that Italian talc which has been tested for purity and offered by us as cosmetic talc is entirely safe for the end mtendecL WHITTAKER, CLARK & DANIELS, IN C July 30.1975 MORTALITY STUDY OF TALC MINERS AND MILLERS G. F. Rubino MD G Piolatto.MD G. Scaasetti. MD C. Romano. MD DEPARTMENT OF OCCUPATIONAL MEDICINE UNIVERSITY OF TORINO ITALY Presented at; AMERICAN INDUSTRIAL HEALTH CONFERENCE San Francisco A pril 14,1975 LoGiudice/WCD/0324 LoGiudice/WCD/0325 INTRODUCTION The purpose of this research is to rsoettain the causes of death in talc miners ana mil!ers. Our study was conducted on a talc mincralcgicdty very pure. All the subjects of our study have worked only in the mines or mills of the talc operations in the Pinerolo Valley. This particular talc is of the hignest standard of purity. When analyzed by X-Ray Diffraction and by Electron Microscopy it has never been found to contain any detectable a mourn of non talc minerals, such as trcmolne or chry til e. Kkdnleld et al. made a Sim ilar study in 1967 in N Y. State on a group of 260 talc miners and millers exnosed to an industrial talc As p an ted out by these authors this talc contorted ither silicates such as serpentine, trem dite, anihophyllit; and other ingredients predomi Tandy car bonates. Tree silica was also present in the dust, usually averaging not more than 3 percent Therefore our present epidemiological study provides a basis for comparing subjects exposed to an impui e industrial type of talc tr subjects exposed to a very pure cosmetic type of talc. TYPE OF STUDY AND DATA COLLECTION We have employee' a prospective historic study cot listing in the follow -up on all m alt subjects who began to work in the years between i92I and 1950 and woo have been exposed for at least one year to talc in the mines or in the mills We have gathered a total of 1514 miners and 478 milters qualified by our definition of the sam ple. in choosing the control sample w? thoughi it advisable to use the method of inatcliing rather than a comparison with national death rates which would potentially involve the influence of nuisance variables (feeding habits, ethnic characteristic differences, etc...! Control subjects were taken from the population of the town of Alba, because it presents the same ethnic characteristics and similar social and economic corditions. Alba is a center, about 38 mOes from the Pinerolo Valley with a dominant traditional agricul tural activity and very Ettte industrial development involving any obvious hazard at occupa tional disease or carcinogenesis to Its workers. For every subject of the exposed group a control subject was taken from the City Flail records with the same s.x and birth date and still alive at the time the exposed subject was beginning his employment. The first control subject meeting these requirements was selected. With the information we had gathered a follow-up procedure was instituted for the exposed subjects who had left employment and whose vital status could not be determine 1 from the company records, as well as for the oontro! subjects. The City Hall registries o f die birth plat or death place provided information on vital status and possibly on cause of death. When the cause of death was not found in the City Hall records or if there was some doubt about its reliability, a further inquiry was started with relatives of the deceased, attending phy sicians (whenever they could be found) or examining the hospital records for hospital deaths. Follow-up is 88.9% complete on.miners and 91.6% complete on millers. Slide 1 show the fol low-up and slide 2 the vita! status of the exposed population and their controls, as o f June the 30th, 1974. The subsequent statistical analysis was conducted on 1346 miners and 438 millers on whom follow-up was complete. As we were already in possession of air dust concentration in the mines and in the mills (this is shown in slide 3) from 1948 till today, we were able to determine for each worker the amount of exposure to which he had been subject. As no change modifying the environment occurred to 1949 the level of exposure was consi dered to be uniform from 1921 to 1949. As you can see from the slide, the level of exposure is quite different between miners and mil lers. Slide 4 shows the distribution of all workers, on whom follow-up was complete, according to the Exposure Level. The Exposure Level was figured out by the addition of the number of particles per cubic centi meter for every year at work. RESULTS Slide 5, Table 4 shows that the observed overall mortality of talc miners is lower than expected. There are 704 observed deaths compared with 791.2 expected deaths, No relationship exists between the Ratio of observed to expected deaths and level of exposure for the overall mortality, all malignant neoplasms, lung cancer and gastro intestinal cancer. On the contrary respiratory diseases show an increase in the Ratio with increasing exposure. This is also graphically represented in slide 6. Slide 7 shows a similar pattern on overall mortality for millers (227 observed deaths compared to 258.4 expected) and in contrast with miners also exposure factor docs not show any influ ence in increasing mortality from respiratory diseases. In miners, as shown in slide 8 :he Ratio of observed to expected deaths from respiratory diseases increases with increasing interval between first exposure and death (latency). All malignant neoplasms decrease in miners with increasing latency following the trend of the overall mortality. The trend of the mortality from all causes, considering the latency time, is reported respectively for miners and millers in slide 9. For millers, as shown in slide 10, no rela tionship exists between Ratio and latency for any cause of death. DISCUSSION The above tables show that the mortality (overall mortality) is higner m the control group than in the miners and the millers. Th s could be due a. to a biased selection of the exposed group b. to a difference in recording mortality in the exposed and in the control groin. c. to the well known effect whereby occupational groups experience a lower mortality than controls taken from general population because of a selection upon starting work. d to a beneficialeffect o ftalc exposure e. to a lack o fcomparability of the two groups. Cause (a), biased selection, ca r be excluded because all the workers who have beer, enrolled be tween 1921 and 1950 and who have worked at least one year (therefore, including a substantial number with a very long period of observation) were included in the study. Cause (b), difference in recording mortality, scent! very unlikely. Methods of data collection on mortality were the same fot the two groups (exposed and controls respectively) and in both groups cases were lost to follow up fot reasons not reiatco to mortality (accidental Jestruction of record files at the local City Hall registries, cat elessness of clerical workers, etc...). Cause (c), selection upon starting work, is less easy to discard, although a definite indication that it cannot provide the entire explanation for the higher mortality in the control group comes from the uniformity of the mortality Ratio during the observation period Assuming that the lower mortal ty of the exposed group is due to selection of more healthy in dividuals, the effect would have vanished after one or two decades; on the contrary it remains practically unchanged for the whole period of observation (see latency tables) Cause (d), a beneficial effect of talc, can be discarded on general grounds and because the lower mortality is present in both miners and millers and uniformly for most c luses of death, except for iexpiratory diseases in miners. But if may be taken into consideration in evaluating the ex tremely low mortality rate from lung cancer in both miners and millers. This hypothesis can be supported by some studies in a c co rd an t with our findings' Kcnnaway and Kennaway and more recently Goldman, Ashley Enterline and Liddell have found a strikingly low rate of lung cancer in coal miners. Similar results were obtained by Oocding who found an incidence of 0.5 % of lung cancer in the autopsied cases among 592 coal miners in South Wales. By contrast Doll, in reviewing ad the autopsies of male subjects in general hospitals in En gland has found an autopsy lung canceT incidence of 6.2%. The hypothesis of a protection against lung cancer induced by organic or inorganic dust was first suggested in 1952 by Kennaway and recently supported by Spelzer who states that expo sure to some mineral or organic dust induces some varying degree c f hypersensitivity reactions which develop an immunologic:.] protective status and enable the host to recognize and to de stroy the cells which altered him imological patterns,(such as carcinogen ones). Moreover, it is well known that inert particles (such as coal, bentonite, aluminum silts) act as adjuvants when introduced in the organism, by increasing the antibody level and macrophage response. Some studies have also shown that hr absence of radioactive or specific crnecrogenic materials (haematite or asbestos) in the ground, no risk of tung cancer excess is present for miners LoGiudice/WCD/0328 Cause (e), lack of comparability, could be the main contributor to the observed differences. As already mentioned male controls were matched by age to exposed individuals and drawn from a population similar in economic and social structure, general habits and degree of urbaniza tion. However, it could be possible that the matched population exhibits (for not easily under standable reasons) a constantly higher death rate in respect to the whole population of the Pied mont region. But this is not easy to verify because of the lack of regional statistical data (so far back in the past) fit for this comparison. It may be concluded that the comparison between the controls and the exposed has to be considered with caution. The lower mortality among the exposed workers cannot lead to a final conclusion and be ac cepted without reserve even if no doubt would exist on the adequacy of the comparison with the control group. However, further insight may be gained by the internal comparison of groups of workers ex posed to difference total dose of particles and by splitting total mortality by cause. For millers no dear dose effect relationship shows up either for total mortality, considered over time of latency, or for causes of death. For miners the only clear pattern emerges for respiratory causes of death; here, in spite of the lower overall mortality in the exposed group, an excess of mortality is present both in the ex posed versus controls comparison and as an increasing mortality with increasing dose and laten cy period Considering the trend of mortality from respiratory diseases in relation with dose and latency, respectively in miners and in millers, it is possible to assume that the inducing factor is the silica rather than the talc. The deficit of tumours in the exposed in respect of controls is supported by the absence of any doze-effect pattern and is more easily interpreted as just one aspect of the lower mortality of the exposed group, although a low rate of lung cancer as reported above, may have an alternative explanation. In conclusion exposure to silica in talc mines increases the risk of death from respiratory causes. N o increase of risk is detectable, under the slightly less than optimal conditions of the study, for other causes of death in miners, nor for any causes of death in talc exposed millers. While Kleinfeld's findings provide evidence of cancerogenicity risk when talc raining or milling is a source of asbestos exposure caused by fibrous contamination, our conclusions support the thesis of no cancerogenic effect attributable to pure talc. T able 1 slide 1 I F ollow -u p S ta tu s o f t a l c M iners and M ille r s (1 9 2 1 -1 9 7 4 ) MINERS Number Percent T otal 1514 100 Found 1346 8 8 .9 Unknown 168 1 1 .1 MILLERS Number Percent 478 Y-> oo 438 9 1 ,6 40 8 .4 Table 2 slid e 2 VITAL STATUS OF 1 3 4 6 MINERS AND 4 3 8 MILLERS -WITH COMPLETED FOLLOW UP AND OF RESPECTIVE CONTROLS (ON JUNE 1 9 7 4 ) . M iners - Number j Percent 1CONTROLS - Number Percent MILLERS - Number Percent CONTROLS - Number -- .. Percent DEAD 704 52. C 851 6 3 .2 227 5 1 .8 275 6 2 .8 ALIVE DEATH CERTIFICATES OBT, 642 667 4 7 .7 94 ^ 495 813 3 6 .8 211 9 5.5 _. 213 4 8 .2 96 163 3 7 .2 254 9 2 .4 f 1 ! LoGiudice/WCD/0329 LoGiudice/WCD/0330 DUST GGMGEMTRATON} N AIR SUDE 3 JUDE- EXP.LEVEL I EXP.LEVEL I I EXF.LEVEL I I I MINERS . 2 .p p /m l/y r < 60000 n o n b e r p ercsn r 405 3 0.1 60C00 -200000 423 31 .4 MILLERS p p /n l/y r zrumber p e rce n t 5000 163 37 .2 .............. 5000-15000 144 3 2 .9 P* 2 0 0 0 0 0 518 3 8 .5 > 150C0 131 2 9 .9 TOT 4L I3 6 100 TOTAL 438 100 4 LoGiudice/WCD/0331 Tat>le 4 Mxms-.amiALL uDcwMxn * M M I ^ O f d D a tf , by I n te m l b t ^ e n M Bposure m ftath $ * * > . SUDE 5 Bpw*! /.O xitrol* G-cpwiisoa XntOTDAl Coa|}&tljCKX3 Tbtal Bxpcae , X^EHCT 4-- ........ ....... ....... 0=-! Ob/Exp 68/842 Rttio 0,81** :i-20 110/110.6 0.22 21-30 203/306.6 0 97 . 31--40 189/207 art 41-80 12(5/157.5 O.tC-* 80 * 8/14.1 3 .- 3*JC1 704/791.2 O.S0** --------- ----- ------------------ * s t i t i --ically laairicaflv t ** Controls a la * Riti j Bip la m I tep 1**1 11 B p I*vel i n Ox/Hip R iti Cbs/xp Riti 0 /S q j Riti 100/83,0 1,19** 127/117,3 1,08 200/200,2 1.03 aao/aco.9 i.io 184/152.4 1,21** 14/8,8 1.57* 731/781,3 1.11** J 38/24.3 >0/33.7 B/7.3 30/53.7 1 41/40.6 3/2,6 231/214.7 1 .4 7 32/23,4 1.37** 0/18.73 o ** 1.12 42/33,4 1.19 28/30.7 0.71* 1.04 60/55,1 1.00 81/87,2 0.83 0,93 r 41/41,4 0 00 07/93.1 1,04 1.01 32/20,8 1 07 33/55.2 0,06 0.77 2/2.04 0.93 6/4.4 1.14 1-0B 200/187,2 1.12* 284/298-4 0.8* * --- L--------------- -------- ] ** 3 t tiin c ll> ligaifioaa et i s iavel T teSt'l j f f i i a a i orawiz. mjbvlijy SUDE 6 c t- a r ^ d w h , J B pee* n t t i br Interna! tmtmm a m topo*,TM 8 a * I-----`----------- ! . u tm x Bposed v. Ctatrol* envanece Tbti Bpossd uoe/Bxp Rutilo Oattroi* Cbl/IO Betio 0-10 I 41-30 i 16/29.6 46/41.7 06/67.0 57.72.5 . 38/42.2 4/4.5 227/358.4 0.54** 43/29.4 1.10 36/40.2 0.87 09/67.1 0.70** 07/71.S 0.9 37/32.8 a 88 3/2.3 0.63** 1 273/243 6 1.46** 0.90 1.03 .sa* 1.13 1.20 1.13** Interna! Ccnpar*cn Ifivei i Cbe/Sp Riti * p levttl II Cbe/Bp Riti *4/7.6 20/10,7 32/27.3 23/21,2 10/12.9 3/2,6 1C2/6B.3 1,84** 2/5,2 1.S0 33/18.5 1.17 20/14.6 1.08 15/10.3 0.78 4/3.7 1.15 0/0.15 1.15 84/52.4 0,38 1.24 1.38 1.40 1.08 0 1.22* Esp I*vl III Obs/Exp Ratio 0/2.9 3/11.0 14/23.7 19/24.4 24/21.6 1/1.4 H/84.1 0 0.27** ' 0.62* 0.79 1,11 0.71 0.73** * S ttiitic a lly ilsniuicinti *t 3 l*el " S U ta ttc ill* algnlflcarit ic Vr 1 -- LoGiudice/WCD/0332 Table 6 XTSES: OBSEHVZD/EXPECIED EEAISS Ai RATIO BY CAUSE SLIDE 7 CAUSE OF DEATH j j' - Infectious disaases i G ^trviiiicsx. M>r*tcs s . Cardjkivasc. K o spirator? , . G astreintest. j Ail ctner causes i Exposed v. C ontrols Ccnparison ..... . . T otal Exposed C o ntrols Exp Level I Obs/Exp R atio Ohs/Exp Rat2 0 Obs/Exp R atio 5G/6 100/120,5 D/20.2 a s /to . 9 3/9.9 208/270.1 142/202 49/59.1 12/11 68/64.7 23/33-5 0.85 0.77** 0.45** 0,32 -0.91 0.73** 1-39** 0.33* 1.03 1.05 0.69** 75/64.5 l .l f 2IA 7 .5 .1.20 155/125.1 .1.2*** 38/31-S 1 19 21A3-5 1 .5T** 3/2.7 1.11 51/49 1.10 19/14.9 1.28 10/9.8 1.02 3/2.8 1.07 J34/2tib,5 1.2** 65/63 1.05 53/97.5 0.59** 28/38.3 0.72* 6S/57.2 1.19* i 'e / u .8 1.08 10 ['10 t 0.99 , 5/4 1.25 60/62,6 43/22 0.96 ' 23/20 8 1.11 7 i * * * ! U /7 .7 . 1.43 * S ta tis tic a lly significant a t 55 le w l ** S t a tis tic a lly s ig n ific a n t a t 1% le v e l In te rn a l Comparison Exp Level l i *p Level. n i Obs/Btp ' R atio Oes/Ex? K atie 15A 4,8 1.01 20/23.4 C. 5 23/25.5 . 1.10 34/41.7 Q.62 1/1.9 is m .i 2/2.3 0.53 ____ I 34 o.eo Ifr/lfl 5 0 K 0.87 4/3.9 1.03 71/55.7 1.27** 71/96.2 0.S2* 38/3/ 1.03 ' 76/67.4 1.13 12/12 7 0.94 21/21.5 0.9S 3/2.8 1,0? 4/4.9 0.81 27/21 1.29 38/25.4 0.70 4/5.2 0.77 8/9.8 0.82 slt^iliceat LoGiudice/WCD/0334 Itole 8 MKEES: GB3ERVH5 JSD EXPECTED DEATH 3 / BflEtWIL BETWEEN' FIRST TXPODORE AK> BfcAlH (Exposed v . O iotroJ Conpi'Viscn) SLIDES CAUSE OF DEATH < 20 ttis/E*p Ratio A ll tumore 19/20.1 0.95 lAisg cancer V I,as o .e i Gestrola te s t. cancer 5/6.9 0.72 R esp irato ry diseases 86/22.5 1.10 u n set 20 - 40 Cba/Exp Ratto 55/73.8 0.76** 0/14.3 0.42** 18/19 0.06 77/54.4 1.42** * S ta tis tic a lly s ig n ific a n t a t S t le v e l * S ta tis tic a lly e ia n iflc a n t a t 15' le v e l > 40 Obs/Ixp 26/3,6 2/4.1 Ratio 0.73* 0.49 13/14.6 0,69 36/25.2 ' 1.43** Itole S SStUBtB: CBSgtVEO AND EXPECTS OiATHS BV ISflSiVAL BET,VEEN ."IRS? EXPOSURE AND DEATH tExposed v . C o n tro ls C anoeriean) SLIDE 10 CAUSE GF DEATH < 20 Cfcs/B R a tio A ll tumors 5/ 10.8 0.78 Lung cancer 0/ 1.5 C G a s tro in te s t. cancer 5/ 6.1 9.98 R esp irnta ry d i6ase8 7/ 8.2 0.85 U 1ES3ST 2 0-4 0 ----------------------------------------- . -- * 40 Cbe/Exp R a tio C ts/Exp R atio 34/ 38.7 0 84 7/ 7,5 0.03 1/ 1,6 0.67 _ .._ . __ 6/ 11.1 0.73 3/ 4 .5 3/ 2.9 0,67 1.03 17/ 11.6 ' 1.47* 1/ 1 .7 0.59 S ta tis tic a lly s ig n ific a n t a t SS le v e l * S ta tis tic a lly s ig n ific a n t a t IS le v e l