Document zQ2nQMkQm6rXVkbooeowmYRn3

FILE NAME: Johnson & Johnson (JAJ) DATE: 1984 DOC#: JAJ 119 DOCUMENT DESCRIPTION: Journal Article - Evaluation by Electron Microscopy Techniques of Asbestos Contamination in Industrial, Cosmetic, and Pharmaceutical Talcs REGULATORY TOXICOLOGY AND PHARMACOLOGY 4, 222-235 (1984) Evaluation by Eie ctron Microscopy Techniques of Asbestos Contamination in Industrial, Cosmetic, and Pharmaceutical Talcs L. Paoletti,* S. Caiazza,* G. Donelli,* and F. Pocchiari *Laboratoro di Ultraslnitture, istituto Superiore di Sanit, Viale Regina Elena 299, 00161 Roma, Italy Received December 9, 1983 Talc.powders from national and international markets were analyzed in order to assess their fiber contents and the proportion of asbestos in the fibrous material. Samples of talc powders used as excipients in pharmaceutical and cosmetic preparations demonstrated fiber contents up to 30% of total particles, /.bout a half of the talc powders revealed the presence of asbestos: in five samples chrysotile (a serpentine asbestos) was present, in the other ones tremolite and anthophyllite (an amphibole asbestos). The amounts of asbestos vary up to 90% in the different samples of the fibrous fraction. About 75% of observed asbestos fibers were thinner than 0.4 (iia, i.e., below the resolving power of light microscopy which until now was the most utilized technique for-evaluating the environmental pollution due to asbestos. INTRODUCTION Talc is a Mg silicate fwvti;th a particular lamellar (sheet) structure in which each lamella consists of one shecet of Mg (OH)2 between two layers of Si04 (1). In natural deposits Mg is often substituted in talc crystals by other cations such as Fe, Ni, Cr, Mn, etc. Deposits are not generally monomineralic, but, since they result from geologic processes which caused the formation of several different mineral phases, they are heterogeneous as far as the kind and relative amount of the minerals (2). Thus, it is not surprising that materials known as talc powders may contain less than 50% of talc (3). The most common minerals that may be found mixed with talc in mineral deposits are listed in Table 1. Among them, two fibrous kinds of amphibole, tremolite and anthophyllite, and a fibrous kind of serpentine mineral, chrysotile, constitute some of the best known varieties of asbestos (2, 4, 5). Talc powders are widely employed in a number of industrial processes and in commonly used products (i.e., in the manufacturing of pottery articles and insulating materials, in paper manufacturing, as additives in asphalts, in pesticides, in cosmetic products, and as excipients in pharmaceutical preparations). It is well known that professional exposure to talc may cause the kind of fibrosis known as talcosis. Moreover, a large number of epidemiological data point out the 222 0273-2300/84 $3.00 Copyright 1984 by Academic Press, Inc. All rights o f reproduction in any form reserved. risk of cancer a and fibrous imj "Asbestos bo several times it An epidemic to fourfold inc general (12). N exposed to talc between ovaria (14, 15). Howi components o In 22 talc r were reported investigators ( analyzed sam{ was constitute Studies car purposes reve; data concerni in the New Y the cosmetic phyllite, and Taking als analysis of ta our laboratoi asbestos in s> European PI different pur In this stu niques such phological ai at high level A small a homogenizii ASBESTOS CONTAMINATION OF TALCS 223 TABLE I M inerals Commonly Associated with T alc in N atural D eposits Carbonates Calcite, dolomite, magnesite Amphiboles Tremolite, anthophyllite Serpentines Chrysotile, antigorite, lizardite Others Quartz, mica, chlorite, rutile, pyrophyllite risk of cancer connected with the fibrous components of talc powders, i.e., talc fibers and fibrous impurities. "Asbestos bodies" in the lung tissue of workers exposed to talc have been reported several times in the literature (7-11). An epidemiological study on workers in talc deposits has demonstrated a threeto fourfold increase in cancer risk as compared with the risk of the population in general (12). Moreover, the same histological lung alterations are shown by workers exposed to talc powders and by workers exposed to asbestos (13). Recently, a connection between ovarian cancer and the use of asbestos containing talcs has also been suggested (14, 15). However, there is a considerable lack of analytical data about the fibrous components of talc. In 22 talc powders examined, values ranging from 8 to 30% of fibrous particles were reported in 1968 by U. S. authors (16). A similar study carried out by NBS investigators (1 7) evidenced percentages from 2 to 30% of fibrous particles in all the analyzed samples. In both cases it was not specified what fraction of such percentages was constituted by asbestos. Studies carried out in the United Kingdom on talc powders used for different purposes revealed that 3 out of 24 specimens contained tremolite (18). More complete data concerning 20 talcs for cosmetic use and 1 for pharmaceutical use purchased in the New York City area from 1971 to 1975 have been published (19): 10 among the cosmetic talcs examined contained, from 1 to 14% (w/w), tremolite and antho phyllite, and two of them also contained traces of chrysotile. Taking also into account the lack of data on the Italian situation, a systematic analysis of talc powders employed or at least marketed in Italy was carried out in our laboratory to determine the percentage of fibrous particles and the amount of asbestos in such powders. Moreover we analyzed 14 talc powders provided by the European Ph irmacopoeia from various geographical areas and to be utilized for different purposes. In this study we utilized electron microscopy (EM) and associated analytical tech niques such as electron diffraction and X-ray microanalysis which allow the mor phological and structural characterization as well as the elemental analysis of particles at high levels of resolution. MATERIALS AND METHODS A small amount of talc obtained from the original package without mixing and homogenizing it, in order to avoid any fragmentation of particles, was weighed and 11 .... III. - U 224 PAOLETTI ET AL. suspended in a solution of 0.5 to 0.8% Formvar in dichloroethane at a concentration of 0.02 to 0.05 g/ml talc. After air insufflatio n by a Pasteur pipet to avoid sedimentation, two or three drops of the suspension were put on a just-cleaved mica sheet and rubbed with another mica sheet. After solvent evaporation, the film including talc particles was separated from the mica sheet on the siirface of twice distilled H20 and collected on 200-mesh copper grids. A thin carbon film was then evaporated on the grids. The samples were observed by a TEM Siemens Elmiskop 102 at 10,000 magnification and 100 kV HT. To obtain information on the crystalline structure of mineral particles, selected-area electro* diffraction (SAED) was utilized. Chemical elements present in the mineral particles were detected by X-ray microanalysis, equipped with a wave dispersion spectrometer. Statistical Evaluation o f Data We checked the statistical compatibility of the results of replicate determinations of fibrous fractions 'or the same talc specimen. The x2 test was utilized to check the hypothesis that the differences in the values of the fibrous fractions were due to chance (21). For each kind of talc the average value of the percentages of fibers and of nonfibrous particles were calculated. The numbers of fibers and of nonfibrous particles measured in each determination have been utilized as elements of a contingency table and x2 was calculated comparing the numeric values obtained and the ones expected (i.e., the corresponding average percentages). At a significance level of a = 0.05, the values obtained for x2 were not generally significant enough Xexp < X2(0.95)] to reject the initial hypothesis. However, in som; cases we obtained comparatively high x2values (xp > x2(0-95)J. Careful reexamination of the specimen characteristics and the counting methods evidenced that the less reliable results concerned counts performed on fields where large clusters of particles were observed or where, due to their number, many particles were in contact. We realized also that the wide range of the counting results could be related to -the lack of a defined threshold for the minimum size required for a particle to be counted. After stating new and more strict counting criteria (particle clusters and particles smaller than 0.2 fim were not included in the counts), we reexamined the same talc specimens and obtained a very good statistical compatibility with the initial hypothesis. In Table 2 the values of x2 we obtained and the ones corresponding to a 95% probability at the same degree of freedom are listed. To check whether the method of sample preparation could cause an increase or a decrease in the fibre percentage, for each kind of talc powder we analyzed the correlation betwee n the total number of particles per unit area of the film (the area of one mesh of the grid) and the percentage of fibrous particles on such a surface. This correlation was studied both on different Formvar films and on different areas of the same film. In all cases the correlation parameter r2 (21) between the particle number and the fibrous fraction in the unit area resulted in values very close to zero, as shown in Table 3. San > 1 ( Statistical A binon number ol fibers. Thi obtain the For a b mean vah and by m The to' ratio ma) of measu Table shows tb deviatioi 5 and 3C Correi ASBESTOS CONTAMINATION OF TALCS 225 TABLE 2 x J Test to heck the R eproducibility in the Evaluation o f the Fibrous Fraction in Talc Powders Sample X 7Observed X2 (0.95) A 9.9 16.9 B 1.61 5.99 C 10.6 11.1 D 7.58 9.49 E 3.65 7.81 F 2.95 7.81 G 0.37 3.84 H 2.34 5.99 1 7.58 9.49 J 3.65 7.81 K 2.95 7.81 - L 4.32 5.99 M 1.39 9.49 Statistical Criteria for Evaluating the Fiber:Particle Ratio in Talc Samples A binomial distribution is expected for the values of the fibrous fraction of a given number of particles and for the percentage of asbestos fibers in a given number of fibers. This allows calculation of the number of particles to be observed in order to obtain the required accuracy of measurement. For a binomial distribution the relative standard deviation (as percentage of the mean value p) calculated by means of the a priori probability P o f observing a fiber and by means of the number TV of observed particles is a/p = [(l - P)/(N ~ P)]l/2 The total number TVof particles to be observed in order to evaluate the fiber:particle ratio may be calculated by means of this equation according to the required accuracy of measurement. Table 4, in which the standard deviation is reported as a function of P and TV, shows that, in order to evaluate the fiber concentration with a relative standard deviation of less than 10-15%, TVmust be about 103, even for concentrations between 5 and 30%, and must increase by at least of a factor 10 for lower concentrations. TABLE 3 Correlation between Particle N umber per U nit Area and Fibrous Particle Percentage Sample Correlation parameter, rJ A 0.22 B 0.13 C 0.03 D 0.13 -E 0.002 F 0.41 G 0.06 226 PAOLETTI ET AL. TABLE 4 R elative Standard D eviation for a Binomial D istribution P N = 100 N = 1000 N " 10,000 of asbestos c a higher con< the certainty 0.01 99% 31% 0.05 43% 14% 0.10 30%'- 9% 0.15 24% 7% 0.20 20% 6% 0.25 17% 5% 0.35 15% 5% 10% 4.3% 3% 2.4% 2% 1.7% 1.5% N - total number o f particles to be observed. P -- probability o f observing one fiber. Since some talc specimens may contain very few asbestos fibers, and therefore are barely detectable, it is necessary to define an upper limit for the pollution level, in case that no asbestos) fibers should be detected in a given specimen. Even in such a case we cannot infer that the talc specimen is completely asbestos free. We-can simply calculate the probability P of finding at least one asbestos fiber among la number M of fibrous particles as a function of the ratio v between the number of asbestos, libers and total number of fibers [jP = 1 --(1 --u)^]. From T a b le 5, in w hich the probability is reported as a function of N a n d v, we infer, for instance, that for very small concentrations (v 4 10 4), the probability of observing one asbestos fiber is very close to zero for samples containing 102-103 fibrous particles. To fix an upper limit for the estimated asbestos concentration in the sample we chose a value of the probability P of singling out at least one fiber of asbestos in the sample of fibers observed: in order to obtain the results we are looking for, we set a 'value-of P = 0.9 (90% of probability). Then we calculated the concentration that, for the number of fijbers observed, provided such a probability (P = 0.9). This value TABLE 5 -PROBABILITY OF OBSERVING AT LEAST ONE ASBESTOS FIBER AMONG N FIBROUS PARTICLES AS A Function of the Ratio v between Asbestos Fibers and Total F ibers U: >0 100 200 500 1000 2000 10-" 0 005 0.01 0.02 0.05 0.10 0.18 .5 X 10~4 0 025 0.05 0.10 0.22 0.39 0.63 ^ 10~J 0 05 0.10 0.18 0.39 0.63 0.86 11 2 X 10*3 0 10 0.18 0.33 0.63 0.86 0.98 3 X 10-' 0 14 0.26 0.45 0.78 0.95 1.00 5 X 10~3 0 22 0.39 0.63 0.92 0.99 1.00 7 X 10-3 0 30 0.50 0.75 0.97 1.00 1.00 10'2 0 39 0.63 0.87 0.99 1.00 1.00 2 X 10~J 0 64 0.87 0.98 1.00 1.00 1.00 5 X IO"3 0 92 1.00 1.00 1.00 1.00 1.00 io-' 1 00 1.00 1.00 1.00 1.00 1.00 Twenty-n uses have be Pharmacop The powi for studies t by light mic even after i The stati obtained fc Accordir particles ha equal to 3 Fibers r< separately, ardous, be' for the evi number of general th< expression To evali amphibole have been The elet not straigl dtermina bole asbes talc powd' The ide through tl electron r Table < of asbestc perform ci concentra For ea< considr and Fe ct fibrous p; As reporl has been were fibe BST, ASBESTOS CONTAMINATION OF TALCS 227 of asbestos concentration in the sample has been considered as the upper limit since a higher concentration would provide a probability higher than 90%, that is, practically the certainty, of observing one asbestos fiber. RESULTS Twenty-nnre different samples of talc for industrial, cosmetic, and pharmaceutical uses have been analyzed: 15 from the Italian market and 14 provided by the European Pharmacopooiia from the international market and from various geographic areas. The powder samples prepared by the Formvar film method showed to be suitable for studies by electron diffraction and X-ray microanalysis and for further observation by light micrp:scopy. Moreover the samples showed a considerable degree of stability, even after reheated observations. ; The statistical analyses showed the reliability and reproducibility of the results obtained for powder samples prepared by the above-described method, According to the criteria accepted by the Council of European Communities (32), particles have been considered as fibrous when having a length:width ratio greater or equal to 3 a:nd a width less than 3 tm. Fibers res;ipectively greater and less than 5 /rm in length have been considered separately, a<ccording to the above-mentioned criteria, which consider as more hazardous, because of their biological effects, the fibers longer than 5 nm. The counts :for~the evaluation of fibrous particle percentages have been performed on a total number of p;articles ranging from 2 X 103 to 10 X 103 for each kind of talc, so in general the resulting error in the percentages (standard deviation calculated by the expression givien in the statistical criteria) was not greater than 10%. To evaluat:e.the pollution due to asbestos in the studied talcs, the fibrous kinds of amphiboles, tremolite and anthophyllite, and the fibrous kind of serpentine, chrysotile, have been investigated (2-4). The electron diffraction patterns of the various mineral phases in the samples are not straightfo:rward (27); nevertheless the patterns show peculiarities which allow determination , with certainty, the presence of serpentine asbestos (Fig. 1) or amphi.bole asbestos (Figs. 2 and 3) (23, 28, 29) among the particles which constitute the talc powders. The identification of the kind of mineral in amphibole asbestos may be confirmed through the identification of the characteristic chemical elements by means of the electron microprobe. Table 6 re;ports the concentrations of such elements in the most common kinds of asbestos, The identification of the kind of amphibole present in the talcs may be performed by means of the evaluation of the Ca (tremolite) and Fe (anthophyllite) concentration s in the mineral. For each kind of talc powder, a sample of 100 random fibrous particles has been considered, We studied the electron diffraction pattern of each sample and its Ca and Fe contents, by means of X-ray microanalysis. As reported in Tables 7-10 the fibrous partiicle percentages ranged from 2 to 30% in all of the talc powders analyzed. As reported in Tables 7-9, in 8 out of 15 Italian talcs the presence of asbestos fibers has been revi^aled, in 7 samples there were fibers of tremolite, and in 1 sample there were fibers of chrysotile. 228 PAOLETTI ET AL. ,.,.' Jf'-r . V". . 6 * .'v '- " , * `X V.Aj^V' sky-. .'. :.y.TV?.'' ^Cv'.'-r -..-W'; ; /* f ' - ,f<"> '*.-/'i `* ~ n^ V * V - - V k *- . <,.. , ' , ''>',.(/: r-*s - v 'iL -*" .* ,, ';''J.S . y v . - ' -S'***U i.< - , ^ 7- ; . v '- '* ' C. <*' 'Y -' '^.f: '-sryA-y% ^p-y-* ;*>, 7T< f\ 7 u .- .V?Yv 1* ,\. S L W n if Y-."**.X'*'" * T --- --*v/ '-- 2 %,r**<''.A i*- ,,*V l '-.. 'A ;',", ,!??.<, J: . " ' i' 9^.'.a03 >ii. s -^ s ^i , 42 '. i; ; - ^'- *> t-'VV'Tr* ^` u S ';S -R -: ' ;S t i l v ; ,7 % i - t , ' " S \ '! ;: 0- ir_p^."' . ii'V !*tV. Ajrj.'vf .' ..:?V '- '-v -;; .. A - v- 1 ir .: y-'.ykV".: ;' '-./-'W:-;,?4-"' ;r-. 'A . ' tii x jii F ig . 1. Electron diffraction pattern o f a chrysotile fiber. . ' ' -V' . A -^-c==*f ::'1-u> 0; B- ;. 'A , -' .#?." J "-' tk /'-A" c ', ;i0:? , , 4 - > ^ ; . r : " 1-, ' . > ; Ca - :,; > ^ V - - . . v . l 'A-'.o: ..- h v' ^ .''??' - ' ' .-' f ` VA , k -r. . v-. iTbM . ' c f. ,,, A '-' Ka- -..- "r^- ,,- f r y ^ i r .V. 4r-%uiK-`r : . ` ^ a ; a a . - ^ V : > ; - . ;. ; q - / A ` -4 / ; . , r ;..: . *>,.-, ^i,;..v . / :;v; ' A. . . ;v .. .. v '.^ r5. - V ' v " ; ; ;/. ' -'..V A...A.- -;.....'.^---- Fig . 2. Electron diffraction p attem o f an anthophyllite liber. 'AV; Hr /- r|?sS^^if=2^w^ ' / O - ' ` <3 ',' -x t . C/ . ` -. - .o r'r1. - ^"P ,'. -0' `V-Vv The pre Pharmaco tremolite chrysotile thophyllit the entire varieties < Interes had a dii Chemic S i0 2 MgO FeO Fe20 3 AljOj CaO KjO N a,0 HjO ASBESTOS CONTAMINATION OF TALCS 229 The presence of asbestos fibers was revealed in 6 out of 14 talcs from the European Pharmacopoeia: in 3 samples there was chrysotile, in 2 samples the amphiboles tremolite and anthfi:phyllite were present, and in 1 sample there was tremolite and chrysotile. In the 2 talc samples containing amphibole asbestos, tremolite and anthophyllite were priesent in great percentages, reaching in both cases about 20% of the entire particulare. Figures 4 and 5 show a few typical fibers of such mineral varieties observed some of the samples examined, Interestingly, abc ut three-fourths of the asbestos fibers observed in each sample had a diameter sm aller than about 0.4 tm, that is, below the resolving power of TABLE 6 Chemical Composition in Oxide Percentage of the Most Common Varieties of asbestos Chrysotili Crocidolite Amosite Anthophyllite Tremolite SiOj MgO TeO Fe20 , ALO, CaO k 2o Na20 h 2o 41.8-42 41.8-42. 0.I-I.6 0.2-1.3 0.1-0.5 0-0.1 0-0.1 -- 13.6-14 49-53 0-3 13-20 17-20 0-0.2 0.3-2.7 0-0.4 4-8.5 2.5-4.5 49-53 1-7 34-44 -- -- -- 0-0.4 -- 2.5-4.5 56-58 28-34 3-12 -- 0.5-1.5 -- -- -- 1-6 55-60 21-26 0-4 0-0.5 0-2.5 11-13 0-0.6 0-1.5 0.5-2.5 230 PAOLETTl ET AL. TABLE 7 Percentage oi) Fibrous Particles and of Asbestos Fibers in Some Industrial Talcs % Fibers in the particulate % Fibers > 5 pm in the particulate % Asbestos fibers versus total fibers % Asbestos fibers in the particulate A 26.5 1.7 "B 5.7 0.3 C 4.7 0.7 D 2.6 0 .3 2.8 0.6 0.8 0.1 0.5 0.2 0.6 + 0.1 <2 8 2.7 4 1.9 <2 <0.5 0.5 0.2 0.2 0.1 <0.05 Variety of asbestos _ Tremolite Chrysotile -- phase-contrast microscopy, until now the most widely used technique for the observation of particlqs and mineral fibers, Tor the talc samples in which the presence of asbestos fibers was not detected, the upper limits chosen for the asbestos content were those evaluated by the abovementioned critertia (90% probability criteria). Such upper limits are listed in Tables 7-10. -It must be pointed out that in all talc powders analyzed, quite frequently, fibrous talc particles have been observed morphologically to be very similar to amphibole fibers (Fig. 6) but easily recognizable by their typical electron diffraction patterns (Fig.'7) (19-23). In the examin ed samples, particles of minerals usually found together with talc (Table 1), in par;icular Ca and Mg carbonates, have been frequently observed; as -already mentionep , until now no attempts have been made to evaluate quantitatively their content in talc samples. DISCUSSION Jt is well known that occupational exposure to talc is associated with a diffuse interstitial lung-sc airing talcosis. Moreover, many experimental and epidemiological data show that the fibrous fraction of talc powders is more hazardous than the platy one because of pi esence of asbestos fibers which contaminate natural talc deposits, The aim of this study is the evaluation of the percentage of fibers and, in particular, of asbestos fibers present in talc powders. TABLE 8 Percentage of FiIbrous Particles and of Asbestos Fibers in Some Pharmaceutical T alcs % Fibers in the particulate % Fibers > 5 /im in the particulate % Asbestos fibers versus total fibers % Asbestos fibers in the particulate A 5.4 0.8 B 8.7 1.0 C 4.5 0.6 D 3.1 0.4 E 3.7 0.4 1.1 0.4 3.1 0.6 0.4 0.2 0.9 0.2 1.0 0.2 8 2.7 <2 14 3.4 21+4 17 3.7 0.4 0.2 <0.2 0.6 0.2 0.7 0.2 0.6 0.2 Variety of asbestos Tremolite _ Tremolite Tremolite Tremolite ! i Percent % Fibe the parti A 6.1 i B 21.6 d C 11.1 ; D 4.9 : E 10.3 : F 5.1 : By mean of the perc In some related to r the need o suitable re taking alsc powder ch phiboles i: utilized in asbestos fi Pi % Fit the pai A 4.1 B 25.01 3.0 D 2 . 8< E 3.5! F 6.8 G 2.3 H 1.5 1 20.3 3.3 i K 4.4 i 1 L 3.: ^1 M 33 1 N 5.1 :ty :stOS olile olile bser- , the >oveJ in rous bole ems talc ; as . eiy JSC V :a! A) ity s. ir, ! ,t 4 .4 . ASBESTOS CONTAMINATION OF TALCS 231 TABLE 9 Percentage of Fibrous Particles and of Asbestos Fibers in Some Cosmetic T alcs % Fibers in the particu ate % Fibers > 5 /xm in the particulate % Asbestos fibers versus total fibers % Asbestos fibers in the particulate Variety of asbestos A 6.1 0 9 B 21.6 1 6 C 11.1 1 I D 4.9 + 0 5 E 1.3 + 0 7 F 5.1+0 6 1.6 0.5 . 5.0 0.9 3.2 0.6 0.7 0.2 3.2 + 0.4 1.8 + 0.4 <2 <2 <2 32 + 4.7 <2 10+3 <0.1 <0.4 <0.2 1.6 + 0.3 <0.2 0.5 + 0.2 ____ -- -- Tremolite -- Tremolite By means of the method described above, it is not possible to obtain a good estimate of the percentage by weight of other minerals present in talcs. . In some samples, a very high level of asbestos contamination was revealed, possibly related to risk for people in contact in various ways with talc powders. This underlines the. need of a deeper knowledge of the characteristics of talc currently in use and of suitable regulations, should the results of this study be confirmed on a vast scale, taking also into account the lack of national and international legislation about talc powder characteristics. The sole regulations concerning the amount of fibrous am phiboles in talc were issued in 1976 by the CTFA: It was stated that talc powders utilized in cosmetics and in toiletries should contain at least 90% talc and no revealable asbestos fibers. TABLE 10 Percentage o f Fibrous Particles and of Asbestos Fibers in T alcs Provided by the European Pharmacopoeia % Fibers in % Fibers > 5 |im % Asbestos fibers % Asbestos fibers the particuh.te in the particulate versus total fibers in the particulate Variety of asbestos A 4.1 0. 1 B 25.01 1. C 3.0 0. >4 D 2.86 ~h 0. 15 E 3.55 + 0. 17 F 6.8 0. 18 G 2.3 0. >5 H 1.5 0. 23 I 20.3 0 . S7 J 3.3 . 38 K 4.4 0 . 43 L 3.7 0.37 M 3.9 0 . 41 N 5.0 0 . 47 2.1 0.2 6.39 0.6 0.83 0.13 1.43 0.25 1.9 0.2 2.8 0.3 0.56 0.13 0.32 0.1 7.7 0.57 2.0 0.3 1.8 0.27 1.8 0.26 1.5 0.26 2.3 0.32 <1 87 + 1.2 <1 <2 <2 <1 <2 <2 92 + 1.3 <2 3 1.2 4 + 1.4 <2 3 1.4 <0.04 21.7 + 1.0 <0.03 <0.06 <0.07 <0.07 <0.05 <0.03 18.7 + 0.8 <0.07 0.13 0.05 0.15 + 0.05 <0.08 0.15 0.07 -- Tremolite 88% Anthophyllite 12% Traces of chrysotile -- -- -- -- -- Tremolite 95% Anthophyllite 5% -- Tremolite 50% ChrysotHe 50% Chry sottie -- Chrysotile PAOLETTI ET AL. Fig. 5. Chrysotile fibers associated with talc particles. 234 PAOLETTl ET AL. As far as talc used as excipients in various pharmaceutical preparations, both Italian and European Pharmacopoeia have so far not stated regulations about analytical control of asbestos contamination. This problem has been recently pointed out and it is probable that regulations in this connection may be enacted soon. ACKNOWLEDGMENTS "The authors are thankful to Professor E. Cingolani for his keen interest in this work. The authors thank Mr. E. Chessa and Mr. D. Batisti for excellent technical assistance. REFERENCES 1. Wells, a . f . 1962). Structural Inorganic Chemistry, 3rd ed. Oxford Univ. Press, London. 2. Deer, W. A., Hovie, R. A., and Zussman, J. (1962). Sheet silicates. In Rock-Forming Minerals (Longmans ed.), Vol. 3, pp. 203-374. London. 3. Hammer, D. H,, Rolle, F. R., and Schelz, J. P. (1976). Characterization of talc and associated minerals. A4mer. Ind. Hyg. Assoc. J. 37, 296-304. 4. Zussman, J. (1978). The mineralogy of asbestos. In Asbestos, Properties, Applications and Hazards (L. Michaels and S. S. Chissick, eds.), pp. 45-65. Wiley, New York. 5. ' Stemple, I. S., and Brindley, G. W. (1960). Structural study of talc and talc-tremolite relations. J. . Amer. Ceramic Soc. 43, 34--42. -(.-Kirk-Othmer Encyclopedia of Chemical Technology, (1969), Vol. 9, pp. 608-614. Wiley, New York. .7. PORRO, F. W , Patton, J. R., and Mobbs, A. A. (1942). Pneumoconiosis in the talc industry. Amer. J. Roentgenol. 47, 507-524. 8. Daymon, H. (1946). Latent silicosis and tuberculosis. Amer. Rev. Tuberc. 53, 554-559. 9. McLaughlin, A., Rogers, E., and Dunham, K. C. (1949). Talc pneumoconiosis. Brit. J. Ind. Med. 6, 184--IS -10. Hobbs, A. Al (1950). A type of pneumoconiosis. Amer. J. Roentgenol. Radium Ther. 58, 488-497. 11. Kleinfeld. M., Messite, J., and Lancer, A. M. (1973). A study of workers exposed to asbestiform - minerals in commercial talc manufacture. Environ. Res. 6, 132-143. 12. Clemmesen, J,, and Hjalgrim-Jensen, S. (1981). Cancer incidence among 5686 asbestos-cement workers followed from 1943 through 1976. Ecotoxicol. Environ. Saf. 5, 15-23. 13. Kxeinfeld, M-, Messite, J., Kooyman, O., and Zakj, M. (1967). Mortality among talc miners and millers'in New York State. Arch. Environ. Health 14, 663-667. 14. LONGO, D. L., AND YOUNG, R. C. (1979). Cosmetic talc and ovarian cancer. Lancet 2, 349-351. 15. G raham, J. and G raham, R. (1967). Ovarian cancer and asbestos. Environ. Res. 1, 115-128. 16. Cralley, L Key, M. M., G roth, D. M., Lainhast, W. S., and Ligo, R. M. (1968). Fibrous and mineral o ntent of cosmetic talcum products. Amer. Ind. Hyg. Assoc. J. 29, 350-354. 17. National Bureau of Standards (NBS) Staff (1977). A report on the fiber content of eighty industrial talc samp|les obtained from, and using the procedures of the OSHA. .18. Pooley, F. D. (1975). Examination o f British Talc Powders. Department of Mineral Exploitation, University o f Wales. 19. ROHL, A. N., Langer, A. M., Selikoff, I. J., et al. (1976). Consumer talcums and powders: Mineral and chemical characterization. J. Toxicol. Environ. Health 2, 255-284. 20. LlNDGREN, B. W., and Mc Elrath, G. W. (1969). Introduction to probability and statistics. Mcmillan, London. 21. H erdan, G. (1960). Small Particles Statistics. Butterworths, London. 22. Owen, D. B. (1962). Handbook o f Statistical Tables. Pergamon, London. 23. Champness;, P. E., Cliff, G., and Lorimer, G. W. (1976). The identification o f asbestos. J. Microsc. 108, 23ll249. 24. Parament er, C. J., and G ill, G. J. (1978). Practical aspects of talc and asbestos. NBS Spec. Publ. (U. S.) 506, 403-411. 25. Stanley, H. D. (1978). The detection and identification of asbestos and asbestiform minerals in talc. NBS Spite. Publ. (U. S.) 506, 325-338. 26. Stewart NBS S 27. Skikne, I asbesti 28. Rund, C diffrac Micro 29. Muelle 2-75-1 30. Hall, 7 Reset 31. CHANDI 32. Council Risk 33. Cosmet CTF WaMlBHMIMg Italian tlytical ut and s thank inerals xriated azards ans. J. Fork. diner. Med. 197. form ment : and ASBESTOS CONTAMINATION OF TALCS 235 26. Stewart, I. M ( 1978). Transmission electron microscopical methods for the determination of asbestos. NBS Spec. Publ. (U. S.) 506, 271-280. 27. Sk.ik.ne, M. I., Talbot, J. M., and Rendal, R. E. G. (1971). Electron diffraction patterns of U.l.C.C. asbestos samples. Environ. Res. 4, 141-145. 28. Rund, C. O., Barrett, C. S., Russel, P. A., and Clark, R. L. (1976). Selected area electron diffraction and energy dispersive X-ray analysis for the identification of asbestos fibres, a comparison. Micron 7, 115-132. 29. MUELLER, P. 1C., and Alcocer, a . E. (1975). Asbestos fiber atlas. Technical Report Data EPA 650/ 2-75-036, State of California Department of Health. 30. Hall, T. A. (1971). The microprobc assay of chemical elements. In Physical Techniques in Biological Research (Ci. Oster, ed.), pp. 158-266. Academic Press, New York. 31. Chandler, J. A. (1977). X-Ray Microanalysis in the Electron Microscope. North-HoIIand, Amsterdam. 32. Council of European Communities (1983). Council Directive on the Protection o f Workers from the Risks Related to Exposure to Asbestos at Work. 33. Cosmetic, Toiletry and Fragrance Association (CTFA) (1976). CTFA Specification: Cosmetic Talc. CTFA, Washington, D. C. Trial iit ; ion, s era] 1 f lan, - l .i1 4 tsc. 1 ? tbl. B tic. if