Document K60qGDJ41EYBqR5LKyGr4O452

Lt; * o 1 a:> . o . . ' .-JM iil.-ttX vo '1.1t.) . i-w-:a n GOSG . '. ; ;:r -to-:isG t h --------------O y e r o n a .... i-17.*.. ... : t a /.o * -<*>: bi* *^Tr c ** 25 ' :::jd oin -d ) .cb tn 6 5 0 r O : l - ......... ' 2'- -' 'tCO nnot-ra-d)'. All-GOYA GT> ' *.0 ; 0\ O; y COMA. . 0 -G L\'K>>!GXD yvM ons 0. k 4' . '' 0' 2 2 . u 2 o ;; AG 2-1.3 'OR .10 0 ^0 REMARKS -00 doys *' .10 ; >?,, '(. e*, r> .0 r'0< ' 0 J T., C . C . .1 . .: '1-o o: g Lon<j ij.CC) iQ 4 . * `0 . o ' i -` y ( -o ) i o ' < q - . :J ,, IQ C " - ..Y 3 *% \ -*\ i X o - ,. 7- 0 . 4V . 5 0 0 9 0 >< A V 0 a 4 2 .0 e i^ '; 0 .' . . 4 . 7 0 0 <j.;Yy;j . , i00 i 1.1 y g 'S 5 ' O . (y u v G e i.V I To ;' 1 0 J - '. 0 . .. ' ' 'i o rs : ?.. y i o o . : ' m a s o t i j m l o m a s .l a /a i .y x .' r x a r t j i .> g .v w h : c y i o : O x ;i?.- 'V-v> & m )iO A?. (llar sh) 'o {Zoil) f ::. Al X ('av< 1/41 O /M 34 0 da y a 4 /2 6 3/ d. */l 459 days 7/3 6 500 da y 550 dayu 60 da 7 / l i . 7 /9 i u/ 0 /3 3 : j 30 1/20 d /H 4/9 7/. U . i *,, /.1 0/.11 1 /3 5 ' i 1/2? 4 /1 7 5 /1 5 8 /4 *A~i-' i-'c: C u aiu av/u rAiVibcv o f ha roc te r s la v in g mo-; othe It ornas. . iV.-.loxi 'Tuvcv of o'r.-vivinyj batoste..'.3 . ` . ' ' *4 * , ` * . V ' i K .3nrvi vor 3 rA 6j G -'ay .-3w ere k illed ou de.y. .Pleural adho dorn* but no timore >. i a CL* Oef\l o - : i.. . 'i'1a ** . <'fi ^ r A.>ti.111 >1 ~ - - ^ * ,, * > -*L , 1 ! 12 _____ i . ' k *> 1 V :''<lo x *` O !. '' ' 1<- '; L<. <! 1 ' 1 O]. r; i l'4o"r ,'*<*i r' . '- -.h : j i' `:;;CSC<v y A- -9 \J i3 ! ----. ( ,r a ii "i ij. o r o n ia 30 ' 32.`34 -17H Or* "'" '-----.30 VvO onop* ' D ! Kf-:ci'K 0'/ lon ^ .h *l *'d. V//j > i l 1 / ' /** V v ,-> `- 6 .9 i C 6 3.5 . . J ..... . ! I. o 0 .? ; ! .*>f . 56.7 /,3 3 + .Lab ^AJi,,> - -- .>.,vii,.>, Lab B A0X si L a b .C j 13X ` tcO :;- 1,j ' m o cu ;U * (Ph.-.so c o n t a ) 1CJC 3 Maj;Jc f i o ld ) SX " X'1` '*O1 1 ' i. ' _ ,,4 a S4mT C b . t k -J 4b 'b-' Cb V s c::r ceri Or CO r.o C3;: to \ oiLDSGc. u e n t e y , Crallev 6 _ T ; O w t :o :: e'oaratine *A J. V .cror. ci w wCiV^' 0 Vb-4. < ^*-Ufi ^ **,-s. ^ W ' * * y* ' ^ 4^ J, X~ -- w 's / w< -Cw c c* Xc* -a '- V " C V C --- r i e s - * a n j . c * C^ / v Vi o o r* c ; ;n -, _ O J A . ft V. * , WV rierosieve r.c-tho ir. : r * ,r ~ 6 -- - o i ** . - -k y . - ' -. Vk -'----- k- '*.*n u. ! am ^ . A " >. :'.borcW - - -k. t \ <- -* r -^ ` 4-' * : d u .b ,, :::c or " ^. ; -iv~ -. W > 4 t , ^ '^ i^ a O A u ca d o n ly C* iO a i t * k-V on roo;oottnc^ic:r.t. 4*b>9 \ati' h chrysettle ir/uccd tumors more rapidly than. ,oit correct;. 1/ . Heat trccrtv.ont of sofa chrvcotile increase; *-''y py *^y' *''/ VIu. "VO t r''* ,'y**,a * y ' **i7^ y C' .A* w i l 4. -- Wfc'- ^a.M O 4 4 'A- - * Vvk. w' w O < ka-m* , vj 14^V* S 1 ^ _ os^ U- < .and carcinogenic response aa c h r y a c t i l e s m o s i t e and crcci- dolif.u. Hence.. hazards atecclnerd rich exposures to asberro: suould bo controllable bv measures to reduce.amounts o.f or tho tn c lev;as a coco lr-vt-! -s w U ^ ^ ^ f v t /* iw C* 11*.> V*/ tl L>O response r:> chrynotflo or easecite, but rumors wore resnonce a: croc;oolite. * '' . w* 7 ** y-- V* <4. >V*--> *Ci*.C**** 1y** -- Soi.r i j- c s _ 'antela +-m * A v . V> 1 k. V u*. b. w^-^--k^J ciaogenic response u :ed orouplas ro V*-^k. M1 . ,W05 j -W'> ' p r.* yt*-k^**pkO * ;-- *s^*- O *w* tA- /-->^ ^--a *1 a. O'*. 4. i t S C l^*b< kt _*. a. J . . . C -_ 3copy revealed a* . -a* W - W W4. ka Cpn **%a k-ak *^i V.-kr-. 4 i ka,' W* . to -c_:;orphor 0o rearer:!::. t* a* i.^O l a Va a * A ka V- rduarrial tyg b * t ^ ^ V- " " 17 i . r . * c i t . ti n *'* .- O . Ck^aVV^lj , t~r y ' - > f **-J -', -- r *- n"> r-> ? ( > <**> s s " * i **> * J t* " r* > v" "* *' " 4.k U--- K & ** *. k* -'w' '*%* ' *--* v o ov o c ii <O *. . Xs* w U . . * V-X-. . % -a . i..^ etnee or tee co i,_.,ny ren o .p --us 4,,'"*,/ w .J-xdb inte.: hamsters , ti... incidence of luna emecter then after benne {A "ytur.e alene,. ; Autor erposrro of fetal ; OC 1', tissue to enraste #* ~L.J^ ***- OX;T ^ ^ *f\* nuiocuG e c u car e m e roas T^vt \ . 2: T>Cs C tH ." C 2 1*1 C r n " ^ T / " c v " 'V C : C 2 ^ -M"aVe i ior cnet eun erano ut ae resetn o li f w-a:Tdb* ' -* es of tren solar,tab li ceriti transfer in tot line- of ptirronary neu at.ont d* k > Vrf C~t X . . . i b . V - -b (.! < * VA V *1 _ _ * , tw -1 U O . A - ^ *"* ^ r \ r* " V - rea were establiero; : > d .< m .eel ,,,, i- * , w >i O 10C'.l e et i4 w J ^ v> O J . J-s-, J e t e.e Ci :o t Hi t> ts n c r Pve.icn t?.d a t th a Hatal and Nons t a l l ic Mine Health. e t A S a ety Sycpoaiai on T alc Dust. Hasr-arda Held In f ' 'akinfftm*, r T1 r*,n T i i o f l t ' a v . *-*' -r _ l Q 7 3l J},v' ' I V J . " 1 - l L i . . *.' & V A f A A i f * f i u V . <t> i * v ^ D ivision o Induatriai Hygiene t. :?? Tori; Stave ) iI liy forasr c o lie ^ W in tho d iv isio n o f Xnduvh^P, Hygiene o f K-ow York S tate and 1 have ; . . th:< importunity to -;o .-hcj* rovorcua otudics o f i s l e workwrs in Haw York S ta U , in clu d in g, c l i n i c a l , p h y sio lo g ic a l, r a d io lo g ic a l end onviron-vr/ntai observations^^* In. ad d ition , vre hav e le o studied tho m ortality expsriencaa firing worker in ta lc saining nr?;' K illin g . in most in sta n c e s, tvs havo had the invaluable opportunity to cosm i, .sto the c lin ic a l with tho snvtrcnmental d ata. In gen eral, w hove kemk "t sustained inhale tic :i ! : s ig n ific a n t amounts o f cc.r3ijr c ia l tid e c u i t <vjt <'fi extended period of t i r a , or where there was a s ig n ific a n t .. a;,: d iis.a freu i n i t i a l exposure, can produco a symptomatic fona ox [,;ViUr,:oo Uilcsiisa Tha cornaorcial ta lc to which tho tn lc workers 'cere ' c ; d ( oritrkncd not only the minorai t a l c , but a lso other c ilic a t e e x-\' . Uff V io le n t i:;3 tre m o lito , `a n th cp h yllite and other in g red ien ts, -- .-Cvv;. .-.n'lv carbonates Moreover, free s i l i c a was often, present in the t e s t in varicb le amounts u su ally not avertn-c* -, sow than 3 percent S p e c ific a lly w ith regard to our o o r ta lity fxuoriencoo ewong ta lc v^rkert, us found in on e a r lie r study o f t a lc workers (minors and m ills r 3) hod 15 or mar years o f exposure to t e le dust that tho proportion* * rsorfcality from carcinoma o f the lung and pic; .. c.or.g theca workers waa fous- time that o f tha general population Ik / ur, the sig n ific a n t fkvcwaeac in incidence of m&lign&ncy appeared in kw .d".n t e le workers, tk.r.-:;iy the?. in th 60 to 79 year- ago group, rather then in tl.o 40 to 59 (2) year ago group This observation in the ta lc workers u zs sc jane w ith those found in a group o f csfcsstos Insulators who had the sens duration o f exposure covering a sim ilar time period (31' Ths asbestos k oche core \ .'d c.n Sncrcof.cd inriderce of irartality freia lung censor in 1 . ki o,o ' ' ' v v o 71.- o ck o u - of c o k ..., :a of tha -, creknk k O 'k fy-aet orA r -r'tonoua among t a lc workers wa* not s ig n ific a n tly d iffe r e n t from that of tho gen oS r population, rhcreae among th^Psbortos ?nr-ulators tho incidence o f gastrcin tau t.la.il jiaiignancy was t iile a n s ly higher rhars th a t of tho general population* `/.'a postulated th at the e a r lie r occurrence of malignancies among th osba^toa in su lators was due to two factors* The f i r s t taaa tha r e la tiv e ly greater carcin ogen icity o f tha ch xysotile asbestos as coaparad to commercial ta lc * The second factor was tha exposure of tha in su la to rs to greater q u a n tities of ch ry so tilo asbestos as compared to tho >* t a lc v-orkora .ho wero expos:d to /se r q u a n tities of cocaarcial ta lc duct *?:hch was admixed with appreciable amounts of tr e n a ilto end ontho phy11.1to asbestos* Cur obsorvaticnc f'avoxc-d the f i r s t factor The e a r lie r ottriy'r1o'4** a lso shored an Increased incidence of deaths due to ta lc pncuroconiosia Zi'.fi/o.t I t s complications* A follow -up etude was made to bring our m ortality data ertong the ta lc w t f e r * un to date and to orovide additional in fcrea tio n not renortea in the e a r lie r study Th pertin en t data i s indicateu 1 ..low* A ll tho t a lc TOrkors employed in 1940 who ir:d accumulated lb or koto yc.'ca o f exposura to conraarcial t a lc dust as w ell as those who cdhiovod a Etini/aum o f lb years o f such exposure between 1940 and 1969 vrara included xn tho follow -up study* Tise group to ta led 2C0 vox/; . , : end i t i s bolievad that the o v era ll number co n stitu ted the to ta l work in tin worker population under study* The data were obtained from a number of ccurc- .;* PI ont records pare examined and the work h isto ry o f each individual vms aoic.j.jza xo include changes of job and s p e c ific years of errployaant* Daath c e x iific a t-.c were tudied in a l l Instances where they wars availab le* Tha records of tho physicians wise had attended the workers p riv a tely were reviewed* Substantial Etcditrl in orr; tiers on tho rosieri t y o f th* nerkert was a v a il able in th > ill.: ; o f til's D?v.'j.i.-a of Indian U,". hygi.i;'- -.cu it n vz-;<i an "d iit ic a a l xo/'rex o ; ta*. Ivoopital record.* Inc;un-un autopsy reports e X h isto lo g ic ;.! pe<JLt&us* vcars examined whemv ?r available* Autopsy or biopsy record warx obtained in 38 o f the 103 ... iith t . A ct-r''-crison was made o> the observed proportional m ortality rate a f r tv,a t h x r r n c if ic causes w ith the e x a c te d ra te s among similar population group; snd way Xwnd satisfactory for a d escrip tiv e study o f th is nature The f a a o v ii.. ' , of observed cor t a l i '*" .ttributed to cancer o f th lung end picnr:. rad ,;X, th.' v'-strointe-atinal tr a c t end peritoneum and cardiac diooKSos woro ted ; the expected m o r ta litie s duo to the obov causes in tho various K v . i S t d w . .-.Tha .expected m ortality fo r th s to ta l group represents the pro a^-di.e-n. of deaths eneag white eon in ths United States duo to the s p e c ific epuc-'s in -th e yoar ;.I65 This p articu lar year was chosen cs standard bocw w ;:o. \ r z r.h.:< :~din year of death among the 1Q2 deaths For each of the h r p*K?iodst tlis median yea rsf namely* 1542* lAXI. ... d2* .1957 end iye>2 wera .X w?;tv'u.> . ................... w _ ,r 2;-i tl-io gro-uo* o-.f 260 t.a.l.c _.workers studied* them t.ors 103 deaths* Tr.r-ri pwx a t o t a l o f 25 deaths from malignancies Of these 25 deaths* 13 w;r; due ,ta lung end pleural m alignancies> 9 were riv:* to ."Intestinal rnd poritc;:c? x:t;%tenancies end 3 wore duo to other nsalig;r.\nci--u th irty deaths resu lted fre ,crwiiaa disease* other than cor pulmonale* and 1 J . ... v.ox-s attrib u tab lo to .ttrstocon iosis and i t s complications* Accidents end cuic.ird-3 cccunted for X' deaths and there wero 16 deaths duo -to other causc-a (Tobio 1) In i average rcgs a t death o f the 108 ta lc workers was 60*3 years with a range of 38 to 84 .years Environmental exposure data was a v ailab le in 97 o f ths IC3 death . (V- m*. Yht naan ru raticn o f erpneure fe r th is group was 24*1 years* vrilh r >. > X; X, I f yearj* lb- d .- .I pe'XominantV/ ' c, t r ^ s a llls n n thop h/lllt carbonate dusts end a sm all amount of free s ilic a Cocparativ dust counts at the ta lc minus ami m ills prior to 1945 and bsstw&en 1946 and 1969 were obtained (Table 6 } o ( v.-crc With-regard to the deaths due to malignancies 12 of the 13 malignancies of thn lung end pleura war carcinomas of the lung and .1 teas e fibrosarcoma Of: tho-pleura* Of the 9 m alignancies of the g a str o in te stin a l tr a c t and p eriton aeat 3 uare cancers of the stomachs 2 vsro cancers o f the l i v e r , l of phich tvns primary hepatoma of the liv e r and the ether s, m etastasis from a $& $trdintestinal roxlignnrcy.j 1 v?as a cancer c i the colons 2 vore cancers of tb-pncre.joj and 1 v?ac u p eriton eal mesothoUctM* ;b.- 3 ralignnncios involving other s i t e s included 1 retrop eriton eal retitv=h;a c a ll ski-coos* Jcchtonic iyrp hatic Icu-:-..oia and 1 Hodgkins0 dicrv>sr. {66-ue 3) The o verall proportional m ortality o f carcinoma o f the lung and pleura four tines kftt Mroaeted C onsistent w ith our previous observation @ sig n ific a n t increase appeared to occur in the ago group of 60 ?o 7v y^ars rather than xn t h i 40 to 59 year age group (Table 2) As 1 have alr.-oaoy mentioned? th is find in g among ta lc workers was a t variruice w ith what v..> hsd observed among asb estos insulators, where the observed val*vi In both th* 40 to 59 and 60 to T9 year ago groups v/are s ig n ific a n tly d iffe r e n t iresr. the- Expected values la .the absence o f adequate rooking data, one cannot access the r o le played by sacking in accounting for tha d ifferen ces in thu occurrence of malignancies* ;.. _ Whan carcinoma o f the lung and pleura was related to each of the s ix $**yar p eriod s, namely, from 1940 to 1969 i t .1$ Important to note that the observed proportional m ortality from carcinoma o f tho lung was approximately' four times as much as the expected m ortality during the years 1945 to 1949 end dropped to approach tho expected m ortality in the years i960 to 1964 and 191b to 1969 (Tablo 4 ) , Tho d iffe r cncec bet'-ien the observed and expected Boxtadity ra tes were sig n ific a n t in 1950-54 and In sig n ifica n t in 1960-64 and ** 1965-69* The improves a o r tc lity eypcrionce b-atwoen^?60 and 1969 and to date (1973) in the case o t ung end pleural cancero is p articu larly pertinent eince environmental con trols hay* resu lted in an appreciable reduction in the ti_ :. '_ dust counts in the minea and m ill , although th e fib e r counts s t i l l exceed cf tf. I." : ths present threshold lim it value for asbestos dust by approximately four to fivn timaa (lab ia 6) This finding in d icates th at the present threshold ) imifc r-cr;-:c'. . : v&Iv.S' <o' > f ib e r s/u i with a fibox' length greater than 5 microns for fibrous is io ....eluding ttem o liia fend r o p h y llite , i s b a sic a lly adequate \:ith regard to cancer o f the g a str o in te stin a l tr a c t and psritoneuu; rong tivs t-...c ..'rk-srs, we did not find any sig n ific a n t d ifferen ce between the ;m ' ; ' cfcf.erv v; end expected values in the o v era ll and sp e c ific ago croups studied ] ' (Tab? ;< Pj '.-sid are co n siste n t with findings reported by K iviluoto and W ;r.0r.g r-.r.thophyllite workers* These findings d iffe r from those > '`t 5 <* **V . r - / whor* a fifnn* fxcant increase in the observed Incidence o f g a str o in te stin a l malignancy was round in the o v era ll and - ( 2) s p e c ific age groups studied * Our findings among asbestos insulators u : to those reported by S e llk o ff, Hammond and Churg.(5) Of iue 29 deaths due to pneumoconiosis and i t s com plications, 20 war* ts to cor pulmonale, 5 to advanced tubsrcuiooi.c c;q 4 to bronchopneumonia The lapsad time from the f i r s t coonercial t e l e uuct exposure to death in th is croup averaged 30*9 years with a range o f 15 to 46 yours A ll 29 had th e ir i n i t i a l exposures prior to 1945 at which time more e ffe c tiv e engineering c o n tr o ls, including wet d r illin g in the ta lc mines, were Introduced* The yarcentage of deaths duo to pneumoconiosis and i t s complications has dscreased It/ more than 50 percent in the la s t 5*year period stu d ied , namely, ,t9.jO'"'69 &; compared to tho preceding period (Table 3) The number of deett)." probably r e f le c t s t.;vj grenier e.;po:;i<>'rv. which occurred 'in tre  (}> years o f enplaymeni* longer in terval must e la p se , IK w v e r , before the f f e c t o f controls cn the incidence of pneuiaoconiosia can be appraised Bare d e fin itiv e ly in the plant studied K; i s noteworthy, however, that in. another study of a d iffe r e n t plans processing a sim ilar mixture o f t a l c , treraolite and a n th o p h y ilitc 9 but wharsin control* were in s ta lle d at the in cep tion of operatic;^ in 15-48, only 1 o f 39 workers had a chest roentgenogram c o n siste n t w ith pneumoconiosis Tho mean exposure of the S3..tiorkers was 162 yc-m: with & range o f 11 to 22 years* Tho worker hose'.Chest rcentoonoorxj was c o n siste n t w ith pneumoconiosis was a 75-year v old can who had a nc.t-yitductiv cough, c Grsrio i dyspnea and who worked ;]ani t or for 11 y r r s . The low Incidence of pneunioccniosis was found eftspite the presence o f r e la t iv e ly high fib e r aid dust counts In th is p l e n t ^ * Hie fib e r tount3 exceeded by two to s ix tins the present threthr!'' vstjt* of 3 fibers/m l with t length greater than 5 microns* In term o f time-woighted avsragos, Jto-pky and a s s o c ia t e s 'r7 found no bestosio among workers exposed le s s than 0 mppef-yearo to ch r y so tile and fflosit in ship con stru ction In ihn study o f the plant having controls sin ce the sta r t o f o p e r a t i o n s ^ , I t was found that an appreciable number o f workers exceeded the 60 nppef-yeare, but did not six any evidence of pneumoconiosis as determined by lira c r ite r ia of Murphy and associates# The findings from the study o f the plant having controls ras the onset of Operations suggest that trem olitc end anthophyllite are le s s fibrogenic than c h r y so tile ox itoosite a t comparable dust exposures Of th 30 cardiac deaths, excluding cor pulmonale, 22 had coronary artery d is e a se , 5 had hypertensive haart disaaco and 3 had rheumatic heart disease* Fwithor surprising wxs the obeouvnlicn that ths observed pro portional m ortality from cerd ^ o was ic^or ihan tho expected t csartsl.'.ty in a l l 5-year period*; except the f i r s t , namely, 19401944 (Table 5)* Xi eesnva reasonable to state, on the basis o f the re lin i n g data that the over o il' observed proportional m ortality from cardiac d isease among ta lc -* - - ' workers was lcwsr than the exofccted m ortality* The decreased m ortality from A. * - r ' ~ ' - ' - ' ' ' * ' cardiac disease among ta lc workers cannot be attrib uted to a p red isp osition tb 'iu n g 'cjn cer which generally r e su lts in the death o f these workers a t e a r lie r eg.os before they might b- expected to succumb to cardiac disease As deircn5.trat ad* ths decreased proportional m ortality from cardiac disease bus'present In both the 40 to 59 as w ell as the 60 to 79 year age groups |Table 2) I f malignancy of the lung was a fa c to r , ona would have expected i d ifferen ce in incidence between these two ago groups* The true explanation fo r the lower Incidence o f cardiac d isease is open to conjecture* The rural Ghv.iromflant in which tha ta lc workers liv e d , as w all as the p o s s ib ilit y that t h e / wXX/XCiu e c s , any aucuuiii. iw. _ t "117/ A" a *'avriifir. n i s e a s e As compared to tho national rats* l c - ------ v - X tru st th at the information I have submitted th is com ing w ill provide tho Bureau o f Mines w ith e s s e n tia l data r e la tin g to tho occupational hazards ***-- . . . . o f exposure to t a l c , fibrous ta lc and trem o llis dust in order to evaluate tho adequacy o f tho e x is tin g threshold lim it values for pure ta lc and ta lc mixed w ith treraolite and enthophyllite* /' ' 1,, icv.z rcc.i-c Ler.xncea cJU: J tle in fa ld , M., M easit*, .?, fh ap iro, J . and Swencicki, R .i E ffect o f vcrrcYalc Dust Iihal&tlon. 012 Lung Function. Arch Environ Health 10* carc'ifen-37,. 1563. *JU ] .E iein feld , K.f Masai t s , J . , Kooyra&n, 0 . and Eaki, M. j M ortality Araong err] i?filc Miners and M illers in New York S ta te . Arch Environ Health Ihi A; c -463*6'/* 1267. v3*- t Iein fcld , M., M assite, J. and Looyoan, 0 . s M ortality Experience in a (7:7- Croup. oC Asbestos Workers. Arch Environ Health 151 177-80, 1967. $ :; iiiv ilu o ta , R. and Mauraau, L, s Results o f Asbestos Exposure in Finland, for 3.80-186, - Ill ti. A. Shapiro, i'd.* Pneutaoconiosis. Proceedings of the cr.v:'International Conference, Johannesburg, 1969. Cape Town* Oxford ih:vO tiivcrsity Press,. I970e Ik. ;gXik0l, 1 J{ ZiSrrsOKdp o . ttno caurg, 01 r.>j. aJ.uy cj-yxzi. vi. Asbestos Ite n la tio a Workers, 1943-1968, pp. 180-186. IN H. A. Shapiro, Sd.8 Pneu'focoaioalX'. Proceedings of the International Conference, c : Johannesburg, 1569. Cape Towns Oxford U niversity P ress, 1970. . ELei-'ifeld, 11, Mcrsite* J . and Linger, A. M. t A Study of Workers ' .Exposed to A sbestifona Minerals in Cosanarclal Talc Manufacture* Environ Ees. Accepted fo r Publication. 7 Murphy, R. L. 4, Jr.* F e r r is, B* G,, Burgers, V. A ., e t a l l E ffec ts o f Lot? Concentrations o f Asbestos;* Hew Engl J Med 2851 1271-1278, 1971. 1 I Ui 1. F.lcir.i t i c . :'.-zzLtc, J. , J , :r.; Tc.lc h e i t A.nrvw*I. u r or. 1-' t 421-37 , ; : . Table 1 /.r er t . k l c l i - i c ; c , t.. , . - i r r r i t e , J . , - r - jf - Talc Mir.crr C att* e* o f Death. In 10S Talc Workers lairing Period of 1940 to 1969 3. K l c i r . f c l c . , Mir: 'Gaus: _ Death.' . . i*A H&Aigrtaneies - . - ; L. : :. - 2/ung and Pleura Q&strointestirial and peritoneal . . A ll other malignancies Ir.v: . . . . ; Cardiac Deaths (other than cor pulmonale) .T.ivcr . . . . Pueumoconioa Ls and f . - ;' xc&croas Accidents cr Suicide Bo. . 25 13 3 30 8``: A ll Other Causer, Total - . w w - `16 " * 108 -. % 23.1 12.0 3.3 ' 2.6 27.8 */ r> 7.4 14.8 100.0 ** Ll r i.r.- c *._ , / is: T illa 2 g~ Crt-up jOeaths and Froportional fetortelitp Frca <'r reIconsas oS. tha EcspirafcQsy Tr&at# th s G astroin testin al Tract# &n Fres Cardiac D iseases Among Tale Workers by Aga# 19 tC-1969 Total Deaths Kr Deaths and Proportional to r ia ilty Fres RespiraTM tory Cancers ) ccths and Proportional !mortality Fron Gastro i.nfcestin a ! Cancera Deaths end Proportional M ortality Pros Cardiac Siseares (%) i> W 'V W W W g ' ' n iw in r ni m n inaiiB B i ............... I B i ,m <w , , |imMM m i .. i m l m i -- i^ U . m u n n i | -min iih m m h m im m i . (%) (%J Ho O b s e r v e d E x p e c t e d Mo O b s e r v e d E x p e c t e d Ko O b s e r v e d E x p e c t e d 40 10-59 60-79 0-84 - Total 3 4? 54 4' 0 4 9 0 108 18 0 8.5 16.6 0 12.0 1.6 5.2 3.6 1.1 3.7 )0 S 6.4 * 7.4 1 25.0 2.5 5.7 ' 7.2 S .3 8 7.4 6.5 4 33.3 11 2 4 .4 17 3 1 . 5 25.0 30 2.8 21.1 4 4 .2 47.S 47*1 45.8  Tab!^ 3 C&use of Death in L08 Talc Workers During the Period 1940*3.969 m i i n T w n 'ii Cause o f Death 3[ 1945-49 , .............. | [ ||i ai ................ i i h h_m j w u --m 1950-54 1955-59 xbbv' 1960-6$ Italic nancies Luna end Pleura Stomach m 2 'l 1 liver l' * tm Cole n Pr:; cress * * s om l m Peritoneum es> m . 49> Other liallgnancie# ** 2 r# Cardiac Disease < 3 6 m Pneumrcccniosis and Complications 2 4 2 Accidents and Suicides 1 1 Others. w* 3 1 Total 7 17 8 o frHinii s. i m. a-- -- a a m a a ^ m * ~ r i m r w M m r u w M H i i n a i .. A-.ho had at le a s t 15 or core year exposure to ta lc djst* 5 1 l <a '*, a* 6 8 2 1 25 3 or- * <! 1 O 8 > s *.v 9 2 5 23 / 1965-69 Total IBW IW <U'IQ . 2 .13 1 2*#& a t 1. ' 1 4 -1 13 7 30 4 1 8^ 6 16 23 108 T - 1f * ''-- -- *' *Tfikt>' 4". i>V: v > !V -.<* . o f' '< )' ' '- V 'i ` Deaths end Expected M ortality from Csoocr the Lung and Pleura end o f the G astroin testin al Tract end Peritc mum Among Talc tforkers 1940-1969 !' i - r- ] rs *^ , r) - -1 1940"-i4 1945-19 I90C-C4 1955-59 1960-64 1965-69 Deaths 0 2 1 '5 '3 2 tunq and Pleura Proportional Mortalltv ET Observed Expected ' -0 - 11 7 - 12*5 20.0 10.7 8.7 2.0 3.1 - 4.3 5.7 6.7 t 7.7 Total 13 ___ P * probability S significant NS r,.&t sig n ific a n t P -- .i -3 -S S NS NS G astrointestinal Tract '.Deaths Proportional snd Peritone'um Mortality . ' --*r P l Observed Expected 1 -1 :1 ii ~ Oi 4l 2 n - 14.3 i 5.8 - 12.5 - 12.0 r 3.6 9.3 r. - 7,6 1 7 .8 - 7.1 i 6.7 7 63 6U A \ N': Nn ! N-`; Hi m>-:* Hi 9 ] i ;a - fable S Deatu and Scpect^d M o rta lity From Cardiac D it a a se etmg a l c Vorktra 1940-1969 / ty 1940-44 Deaths tror-cxtional M ortality (%) Observed E jected M--<WMW-- I--WMMWWfc^-- i----BWmBamMWria'IWl*^C3^SJMA1WWaMan $t 42.8 S*.4 1945-39 3S.S 41.0 1950*54 9 46.0 1955-39 1950-64 1965-69 \ . ta* s %' S0.4 *v.o> 46.6 45.5 T otal 30 1a51e 6 Comparativo Dust and Fiber Counts a t tic VarJoin Talc Elaling sr.d nili n j Operatlcna - Pro 1945 throuah 196? Dust Counts* 1972 /' Dust Counts* Fiber Coun Pre 1945 Ave ** 1'ed ** 1946-1965 ` Ave* Nod* 1965-1969 Avo Mad** Ava o** lied.** Drilling Kuckir.g Crushing Screening 818 413 120 30 Pre 1948 ISO 69 69 61 53 55 1940-1965 42 13 37 $7 19 19 99 3 29 Mi 7 7 3 3. 35 . 15 <*. ' 3 2. 62 M illing Garnering & Separating Pulverizing 92 278 -- 75 25 20 70 27 27 -- 23 28 40 24 ---- ---- 1 - ' 13 . ? 9 20 27 . Bagging ` 151 129 27 23 RR & Truck Loading 73 63 Blew Roora*** 1227 1196 29 25 43 20 27 > s27 36 28 47 2# - Open Chutes*** 125 83 *Dust counts in mppcfj fib er counts in no* fibar$/mI*>Si in length **Ave - averagej Med. - median -Operation discontinued after 1948 L-, -, l \ 11 .{ / / i' LJ ' V--V'* l i -.'a''j7? 0, ;ii jow, l/I o d l i . t*n {c `'deicciive w *>. 0or1i)* . M VT'**. ,\ I. List siimene; 1 walV'-d through a u.ics plant f<.;.t " how dlistv li was 1 oaovj ooc ot m ; p./O'i 0>;:.ici Gevei,..'d lung, t u mb le ,,fmr v.orkiiig there t several \ cars. V A:\ti : ic piarit itself e rdr seemed Lu r!y c! 1**.1 Howe\ er, :hi s I wal ked O' .initio. 1 saw piled g.-inst a shed a mi,'mirri 'i open sacks 1 -Irish powci aad r.ic was talc t \v,i s io be coded ,j Sue c.lay. A sir.; ii j rj c m sin red the m i >ce of the talc- p ifk rc; u p sonic us" and hlowin; it th muihout the kick yaid. Some blew :i*o rr.v face no onto my clot] Co, I a ..ked whether he w or kme n ir.hr. 'd *.de talc, and the inmver ni (ho manager, who appeared ir. intelligent a nd carpii i men, sug- f* * r \ r? V -> ) > >t > . fi f C| * - ! -- 'X'"' f'* '+ :uir-d n o hazard. I worried about this since California talcs, as well as other talcs, are rnixluies pi minerals, of which a large percentage is asbestos. Asbestos ^causes lung can- i- H by R. R. MEELISS, M.D. ccr i n . workmen wh o inhale it, end, interestingly enough, these worhr \en also have an increased incidence of cancer of the gastrointestinal tract, par ticularly of the stomach. Then, with this entire subject siiil fresh in my m i n d , I w e nt s hoppi ng v. ith my wife at a market near our beach home in Laguna. Theie is a Japanese population in Laguna, r u e this ticular market carries food mier.c.ed for the Japanese purchaser. 1 was star tled to see a sack of r ; :e intendevi for Japanese consnmptiori in,ring on the label "ccntcti with glucose ann talc.'1' Japanese people have a h :gh cidence of stomach cancer. Tak coating on rice me an t that the Japanese, at Ir.-ist in the Lns Annetcs area, were eacing talc with their food. The obvious question was whether the two facts were related. Later, in Los An; cles 1 visited several mnikets. and in each I found that rice intended for jrpanete '/7 '#//' ih f"7?\ ^ Y V - Vg a 'V * W c o n s u n i p i 1on bore toe label "coated with glucose and tatc." The next piece oi information needed was how widely used talc-coated m.e is in japan itself. 5 found I could ne; Luy Japanese im ported rice in Los r.r.ceies. The United State:-, at least in ti i , . .on, does not i m port rice iiom Japan. However. 1 bought a sack cf California-produced tdc-c cated rice, and waited several stores in t i e Jnr.,-tne a aiea of Los An geles, asking n eac! case the Japanese own er whether tins is the type of rice commonly u aid in japan in each case he told n r ' that it '..'as. Beginning o' a hypothesis This, hen, lepresenteu trie genesis ..f .. i.......> > - > ----- J : ~ S..VS nJ . 0 i . 4 c:cicr.cv ol caruer ut tr.; stomach in Japanese dun to their eating of asbes tos-contaminated talc adhering to the rice, The fmt ber devel opment of the hypothesis lad me *o t p e n d a n u mb er of evenings away from home reading relevant studies. I learned that the age- adjusted rate of cancer of the stomach in Japanese men from 1002 to 1063 was the hig! est for all nati ms. it was 67.96 per 100 thousand men and was seven times the frequency of that in men in the U-ritr-d d a t e s . Investigation of the Oflgin.il report on the health pr ob lems of asbestos workers by Irving Selikoft of Mount Sinai Hospital showed that the wor kmen exposed to this mineral had a significant increase in gastrointestinal cancer, especially A n ir.!rr:iisl. Or M rrinv has been in f/TiVOfe p re, ' 5<* 10 till s orco. TC f n/*, n .i, i r: n n 1:tln<; </ f.v . -, ,1/1, . t u u ' u t b ' / r o t t i u j - rT / i - -i ! r r r <" t i c i r s H-.V t/ . 11 r ' ,s .>e >/ /<>(ir- nu/-. I'. ..( ;: , t -,.1ni 'icUif' uj tv\a put'll:,hi (i u, V, i f r i nniiiiiiTirinii iKi o n i i m iin mu' vu n r mu iniiinrn i forms of asbestos. T!>> ciitternr *- -A *? v -rm p M y w N tween these two minerals is no, in *;:c:r chemical composition but lather :n their structure, asbestos being hbious while talc is flaky or gtanular. Composition of talc There is no firm commercia1 ci,:::v- tion tor talc.. The c ompos i t . cn of cor- } - <J , -.`'-A ' ' 3 y' mereiai talc varies with the eoe Vermont talcs are sau! to do a arar. e .m type of mineral relatively fro? cf a s bestos. while California talc conta.:'-, fibrous silicates, classified as amp:i,- bole asbestos. Talc minei.x a nd processors rievtbop a lung disease called talcums, just , s A ^ asbestos miners develop asbostosis me lungs, i nere is a egou ctet o: s i m i larity between talcosis a nd asne tests. stomach cancer. Presumably ihe in In one s t u d y ' older talc w u ' k-.cs crease came from the inhalation of fi showed more than four times the e x bers of asbestos, which then settled in pected incidence of lung -'.id p .e u n 1 the pharynx or the nasopharynx (mat cancer. The presence of pi urei ca: - part of the respiratory tract shared with cer, or mesotbeliomnta, is cap ?ciali\ ;r the mouth], a n d were swallowed, b e vealing, since this p a r t i t i l a - typo o; coming trapped in the glands of the tumor is very rare, a nd occurs p r i r :- stomach, causing devel opment c. c an ily as a result of asbestos i u b al a 'if o cer there. Autopsies cm six taic workers with Rice me a nt for the American c on trlrosis sliowed the presence of {.'.* sumer is milled mechanically. On 'be characteristic. " asbestos body" ui other hand, California rice prepared tings of ..very o ne .2 This is a liber ' for the Japanese c onsume r is treated asbestos, coated, with iron-containing with glucose, which forms a sticky him, protein matt-uni. which will give a to whi ch tfit* talc: is applied. The talc positiv c stain feu n on . is nioirght^arpi.-AfiTrtlTTTiac'or of the Up to 30 per cent of various talcs, rice. About 2 per cent of all the talc; d e p e n d i n g on their points of ompr.. produced m the State of California from arc classifiable as fibrous .silicates, 1 8 5 9 to 1963 was used as a rice a d d i winch are largely varieties of om nn:- tive. I had a sample of the sack of rice bole asbestos. Cluysotilc. the vlass.fi 1 bought exami ned St udy of the ash form of asbestos, has a fiber more -uo.- demonstrated (lose to about four mil able for weaving ;u! h a s !, eei lion .ishe-.to., iiiir.i i.Iht-- p w gram. ma k i n g asbesto', i >. t . e n s , h ! u 1 h u m ! t b. , i !! i n u u . a l t.de is d e so bu ih Clin \ \ r T i i e ii .>n t fined m the geologic texts as a hyUiivox as a i ont.munnnt b t ile. silicate of magnesi um. So are some: However, a mphi bol e asbesto^ tih.r.. I l.'o ond I n.iUii/M.utti ui73 . . , " the i n iormn fiif^T c o l l i d e d a p pe ar ed t o . s u p t h e hyp O! that catinp rice mated with ashnslos-contaniinated talc might contribute to cancer. -' which ere usually shelter ttian r.hryso- history of talc coating of rice m Japan. it took us so long to recognize tlv.t Si'e fibers, are ;m safer In one study l While storekeepers have told me that smoking causes cancer. The Into it p e saw from Holland amphibole asbestos to their memory, talc-coated rice was riod between exposure and dm clop- mineral predomi nat ed in asbestos customarily eaten in Japan, informa raent of the cancer is particularly long bodies in the sp u t u m c.f a group of men tion directly from official sources in with asbestos. In one study 1 lung eAposed to asbestos and haying a high Japan has been slow in coming. When cancer appeared more than twenty' incidence of M a l y , a n t tumors of the it fir.,*.My did .,,me it was incomplete years after the begi nni ng of o c c u p a pleura (th r ncmbr.w' that lines the and only [snc.dly revealing. 1 have tional exposure to asbestos n i n b i i s i lungs ar.d chest cavity ]. Moreover, m i n learned that talc-coated rice, was the In another s t u d y ' the increi.se of lung, is;:'. of '.Mr that con'v.r.s more ampbi- classical form of Japanese rice prepara cancer first a ppear ed about ' wer,t\- bide as K stos -,hcn cbrysotile have a tion in the past. However, officially, five years after first exposure. substantia'1 m e rr a- e in t! e i ncidence of this has st opped in recent years, The Consequently, I expect now, shcviiu c.incei of the lung Japanese Ministry of Agriculture and the hypothesis be correct, that s o m e At ibis point the information I col Forestry' writes that with enforcement time ir, the future, after the expi'.aiir:. lected a p p ea r ed to sincport th? liy- of food sanitation laws in 1947, the of the latent period necessary for wr- nrtthesis that eating n e e coated with addition of talc to rice has stopped. cinogcnesis, cancer of the stcm vrh rslmstns contaminated ode rnuyht con- This same Japanese official source Japanese in Japan will begin to ,c t . ib Ui.C IV) , - . indicates that there is no current c o n crease. Exactiy wh e n this crop- o; curs The newt Wep in th * investigation tamination of rice by talc. I have had will d e p en d on the length of the Liter.,. ,, t i' i. . . V . 1 - . . . - , _ --------------- ------- - - jn . i iu ti , e m u vnti ikiws v v m ; u ,,u gcograpmrai occurrence. st udi es ported trom Japan or purchase:, c.:;;: application of talc to rice >n Japan within J.yau showed that in prefectures by visitors, examined for asbestc Four stopped. in which ec.t. is the major staple, s t o m of these d e m o n s t r a t e ' no asbestos. The value of this hypothesis, t r - n, ach cones i h'ghor. it is lower wfiere However, one s peci men of canned will be decided by the death to (:> m the p op u 'a t io n eats heavily of other cooked rice, currently prepared and cancer of the stomach in Japrr in `w staples such as soybeans or yarns. The cooked in Japan a n d imported to future. Consequently, the next u n ye -rs death rale from stomach tumors is America from Japan, contains a s u b will tell whether this h y p n '.imsii :? greater in Japanese who eat rice with stantial a mount of asbestos, even after valid. If the death rate drops, U v. Pi every rwe! than in Japanese who eat it the cooking and washing process. be st r or yl y support ed It not, one win nfw tc frc.'i ucnt !v . Consequently, it would seem that then have to conclude that one ;ni:c Fintdiy, the stomach-cancer i nci while the use of talc-coatcd rice in seemingly attractive hypothesis on the dence of Japanese cannot he c ons i d Japan lias officially been abandoned, a: genesis of a form of cancer will h a w ered a hereditary or genetic disorder, least one sample of rice from japan is been disproved. since as Japanese migrate westward, still currently contaminated with talc. the intitlerice of stomach cancer falls. At the moment , then, the hypothesis RKFcKEMC.ES Thus the incidence of stomach cancer among Japanese in Hawaii is greater than among their non-Japanese neigh bors, but is roughly only a little over half as much as m Japan. History of talc coating The most difficult as pe ct ' of the tiev e m p i ' a n t of th' hypothesis was the t e'er:!!ie,,'in-n of lie u.iiure of tin; rice <ui rcut Iv iiei. ig eaten in )ajan, and the remains neither proven nor disproven. With all carcinogens, or co-carcino gens (other substances that woik with carcinogens to cause canter), tiic pe riod between injury anti the develop ment of clinical cancer is always long. In the human living such a period be tween injury ;,m! development of canter may run up to tumPy to tliiitv years. Ti ns is w.iut m Mes the un n b l eat son of cai taiiogeeu ih Itirult, anti why' 1M K U m i d i ) . ' M * " --;' r`* O K ucyrrm n M Z.iki. Morf.ili fv ... 'iint; t n l r m i n t ' s mi ! !< *r v m N m v V r i > ^ ` iti- A t h Ln\ n o n H e a l t h 1 4 1 4 . I (,C>7. V h , ; 7 --------- _ t C C n I. J . M i n ' , . 11n r ,, v L i , m i d j \ i r v s i ft- 1 .ilc P i i a m i u f o i i u a - i r t p i rt o f < \ p . i f k m *v u h h p i ^ l n u i i i c m f t i inu;*; A r e ! > i r u i r j t x Health 7 1 U M 1 5 . I'lf.'i 3 l. S r l i Ko f i . | C h u r p . . mi ! 1 C }I i i n r n n m i V * .< ns e x p o s u r e .nul n*t<pi isi. / \ / 1 y . '2 ?<*. 1<<0\ * | ' k . t o ' i , d i r / M u t ' . i d , ( m i A l u n i . , , u i - i j ofi'CI .1/ri-ll l**' hit' (,i< lui > . i 'l ( / ('(.(I, / ' l i f . . '"'' N< / . '" Lifo a nd Ho.altn 'March 107b Alii) E / December 17, 1971 MODIFIED FDA OPTICAL FOR ASBESTOS IN TALC 1. The method is essentially similar to the procedure as outlined by A. E. Schulze and Vi. V. Eisenbcrg of the U. S. Food and Drug Administration, Washington, D.C., August 20, 1973. Considerable experience is necessary to obtain a uniformly well-dispersed sample on the slide. 2. Equipment, etc.: A. Leitz Orthoplan Petrographic Microscope. ' B. Magnification 500X. Resolution is 0.4 micron, t1 ) C. Diameter of field at 50 OX is 0.3 50 mm. D. Area of the field at 500X is 0.0 9 6 m m 2 . E. Area of 100 fields (which are taken at random) is equal to 9.60 m m 2 . F. Use 1.8 x 18 mm square cover slip over 1 mg of sample. Area of the cover slip is 342 m m 2 . mn i t n n i v n v -s4 for total number of fibers in 1 mg sample. H. If the population of asbestos is heavy, only 5 to 10 fields are necessary for counting which is then extrapolacaa to the entire sample under the cover glass. I. Use OdHA definition of fiber: 5 microns or greater in length and a length-to-width aspect ratio of^at least 3 :1 . (1) N o t e : 500X magnification is recommended rather than the approximately 400X of the original procedure in order to (a) assure Becke Line determination; and (b) field contains fewer particles and is less confusing. It should be recognized that theoretically we could observe at 500X some fibers which might not be determined at 400X, thus resulting in a slightly higher "asbestos fiber count" than for the same sample observed at 4 0 OX. 3. From a petrographic viewpoint, we prefer to go immediately after "culprits" with appropriate index oils rather than the two-slide method as proposed by Schulze and Eisenberg AND i* ,3. -- n -* ? `8'"a ?v*? - , i 3 I f ; 1 , <S J % i' UcvOi'. No. vw / Page 2 in which asbestos fibers are counted relative to talc in dices of refrucr-ion. This method presents too many tech nical (optical) problems and can be misleading. For example, if sepiolite fibers are present, and using the FDA 1.574 liquid slide, these fibers have to be counted as chryso ;ile. 4. Be sure the material is essentially talc. Use liquid with n of 1.590 for confirmation and at same time look for apparent gross contamination. 5. The Becke Line is extremely difficult to interpret on fi brous-appearing talc. More often than not, there is d i s agreement among petrographers in the same laboratory on precisely the same fibrous-appearing talc particle as to whether the Becke Line is moving in or out. With experience, however, the talc particles standing on edge can readily be determined by the relatively high interference order color. Also, in an oil of 1.556 under plane polarized light, the particles will match the oil from an angle of approximately 450 to 80, but never in the N-S or E-W directions. 6. If not present as large bundles, the most difficult asbestos ^H ^^ 1 Ci J L * U to L . L l U J . i l td J. nJ i i J. v o kj _u _i_uu x 1 1 exhuliix AA ^ k \ direction) we use is1,556. Prepare l mg s u a e wren r.acb oil and proceed with determination. Under conditions of crossed Nicols and near maximum light intensity, proceed to look for chrysotile showing maximum interference color at 45. Now check for parallel ex tinctio3a. Switch to plane polarized light, reduce the light intensity and iris diaphragm for contrast and check the gamma index. If fiber is chrysotile, it will nearly disappear or show Christiansen effect for gamma index. Rotate the stage 90 to get rela tive bearing of Alpha index. The fiber should now stand out in high relief with Becke Line going into the oil. Then check for positive elongation. 7. The most common asbestiform amphibole to be associated with talc is tremolite. Prepare 1 mg slide with 1.622 oil (gamma index for tremolite) and proceed with determination (now, all non-tremolitic particles stand out in high relief). Go for t r e m o l i t e 1s most characteristic feaiture which is in clined extinction of about 10 to 14 (gamma index to the Z direction). Ac position of extinction check for gamma index. If these match, rotate stage 90 to get relative reading of Alpha index which is below 1.622. Confirm tremolite with positive elongation. Report No. VW73-G2 A Pagt^ 3 8. If Step 7 indicates the presence of araphibole fibers other than tremolite by differences in extinction angle or index of refraction, then these can be determined by routine petrographic methods. Once species is established use same procedure as in (7) (1 mg of siimple on slide in a characteristic oil of the mineral for counting purposes) giving dua allowance for differences in extinction angle and elongation. Reported by \ ^ 'uh y V. E. Wolkodoff 7 X Determination of In a p p lic a b ility for A Regulation Entitled "Asbestos-Form P a r t i c l e s in Drugs fo r P a r e n te r a l In je c tio n " The en vi ro nm en ta l ass e ss m e nt of t h i s a c t i o n has been accomplished on the b a s i s of a complete Environmental Impact A na lys is R epo rt . None of the Department o f H ealth, Education, and Welfare i n i t i a l , c r i t e r i a were met. C > / ? ^ / S . C h r i s--t-o-p--h--e-r----S-c--honwaider, Ph.D. Primary Action Officer Enclosures: Environmental Impact Analysis Report Environmental Assessment Report  * ENVIRONMENTAL ASSESSMENT REPORT A. Summary of th e A ction The Food and Drug A dm inistration (FDA), based upon accum ulating evidence th at p a ren tera l in j e c t io n of a sb e sto s fib e r s may be harmful to human h e a lth , promulgated proposed r e g u la tio n s on the u t i l i z a t i o n o f a sb e sto s f i l t e r s on September 23, 1973. These r e g u la tio n s have been m o d ified , are now in f i n a l form, and attem pt to minim ize a sb e sto s contam ination in p a ren tera l drugs by: (1) elim in atin g the use of asbestos f i l t e r s in the manufacturing p ro cess where p o s s ib le or (2) req u irin g an appropriate n o n -a sb esto s f i l t e r downstream of the a sb e sto s f i l t e r to m aintain a s a fe and e f f ic a c io u s product. Only w ith s p e c ia l perm ission from the appropriate Bureau w ith in the FDA w i l l the u t i l i z a t i o n o f an a sb e sto s f i l t e r w ithout such subsequent f i l t r a t i o n be perm itted. B. E valuation The attach ed Environmental Impact A n a ly sis Report i s com plete in th a t i t l i s t s a l l o f the e f f e c t s l i k e l y to occu r, and i s accu rate in th at i t d e scr ib e s the expected r e s u lts w ith in the lim its of e x is tin g knowledge w ith resp ect to environm ental r e la t io n s h ip s . The a c tio n and secondary e f f e c t s o f th e a c tio n have been evalu ated a g a in st the Department o f H ealth , E ducation, and W elfare i n i t i a l c r i t e r i a , and no e f f e c t s approach th ese le v e l s o f s ig n if ic a n c e . The b e n e f it s to human h e a lth l i k e l y to be d erived from t h is a c tio n , th e r e fo r e , g r e a tly outweigh the s lig h t e f f e c t s on the environment (th e consequences o f p ro cess ch a n g es). A ll reasonable a lt e r n a t iv e s to t h is a c tio n do not accom plish the h e a lth o b j e c tiv e s o f the chosen a lt e r n a t iv e s , nor do they r e s u lt in l e s s environmental impact. 2 C. A p p lica tio n of I n i t i a l C r ite r ia 1. N atural Resource U se. The r e g u la tio n does not meet t h is c r it e r io n in th at i t could not cause a 1% in c r e a se in m ineral or f u e l consumption n a t io n a lly , due to the sm all s c a le o f the in d u stry b ein g r eg u la te d . C onversely, a s lig h t decrease in t o t a l a sb e sto s mined w i l l r e s u lt from t h is r e g u la tio n . 2. P o llu tio n . This r e g u la tio n does not meet t h is c r it e r io n in th a t no id e n t if ia b le in crea se in ambient a ir or water p o llu tio n w i l l occur from the a ctio n or i t s secondary e f f e c t s due to the sm all sc a le of the se c tio n of the in d u str ie s to be a ffe c te d by the reg u la tio n ; nor w i l l any em ission standards be v io la te d by any r e s u ltin g s h if t s in the f i l t e r production in d u str ie s. S im ila r ly due to the sm all nature o f t h is a c tio n , no id e n t if ia b le in c r e a se in w aste or sto ra g e w i l l r e s u lt from the prom ulgation and implementa tion of th is regulation. 3. Populations. Although th is regu lation i s designed to dim inish the p o ssib le adverse h ealth e f f e c t s of asb estos in je c tio n , a change in the o v era ll age c h a r a c t e r is t ic of th e human p o p u la tio n to the e x te n t th a t requirem ents for h e a lth , ed u cation , tra n sp o rta tio n or w elfare s e r v ic e s would be a lte r ed probably w i l l not occur. Although th e number o f people r e c e iv in g p a ren tera l m edication s in the USA a t le a s t once in th e ir lif e t i m e i s in d u b ita b ly q u ite s i g n i f i c a n t , th ere i s no way to q u a n tify a c a u s e - e ff e c t h e a lth r e la tio n s h ip w ith the p o s s ib le presence of a sb e sto s in th ese m ed ication s. Even q u a lific a tio n of e f f e c t s i s s u b je c tiv e , at b e s t. I t i s hoped th at th is a ctio n w ill resu lt in a health b en efit to a portion of the population receiving in jectio n s on a routin e b a s is , but not even the most ardent supporters o f lim itin g reg u la tio n s would claim th a t a sb esto s fib e r s in p aren teral drugs has a d e fin ite 3 demographic s ig n ific a n c e and th a t th e removal o f a sb e sto s f ib e r s from th ese products would cause human p op u lation parameters to n o tic a b ly change. 4. S e r v ic e s . The r e g u la tio n i s w r itte n in a manner to avoid the p o s s i b i l i t y o f removing an important p a ren tera l product from h e a lth s e r v ic e s . T h erefore, no change in ca p a city fo r h e a lth s e r v ic e s w i l l r e su lt. 5. Human V alues. No e f f e c t on any h is t o r i c a l str u c tu r e s or endangered sp e c ie s w i l l r e s u lt from t h is r e g u la tio n , nor w i l l any fe d e r a l, s ta te or lo c a l standards be v io la te d by the r e g u la tio n 's implem entation. D. Recommendation Whereas t h is a c tio n and the e f f e c t s o f the a c tio n do not meet any i n i t i a l c r i t e r i a , i t i s recommended th at a D eterm ination o f I n a p p lic a b ilit y be applied to the promulgation of the regu lation e n title d , "Asbestos-Form P a r tic le s in Drugs for P arenteral In jectio n ." ENVIRONMENTAL IMPACT ANALYSIS REPORT 1. Proposed Action a. Purpose of the Action The proposed a c tio n i s th e prom ulgation o f r e g u la tio n s lim itin g the use o f a sb e sto s and m icrofib rou s g la s s f i l t e r s from the p a r e n te r a l in j e c ta b le drug and drug in g r e d ie n t manufacturing p r o c e sse s by means o f Food and Drug A dm inistration Good M anufacturing P r a c tic e s (GMPs) fo r th ese in d u s tr ie s . The purpose o f t h is a c tio n i s to m inimize th e presence o f a sb e sto s and g la s s f ib e r s as contam inants in in je c te d drugs. The d e le te r io u s h e a lth consequences of in jectio n of large q u a n tities of these types of fib ers has been demonstrated in lab o ra to ry anim als, and thus prudence d ic t a t e s th a t human exposure o f t h is nature be m inim ized. The r e g u la tio n accompanying t h is EIAR s t a t e s th a t no a sb e sto s c o n ta in in g or m ic r o -fib e r g la s s c o n ta in in g f i l t e r can be used in the p reparation o f p a ren tera l drugs or drug in g r e d ie n ts in human use and a llo w s fo r a 12 to 18 month period o f p rocess ad ap tation to permit the manufacturer to determine the best su b stitu te for asbestos f ilt r a t io n without s a c r i f i c e in product s a fe ty or q u a lity . Should no s u ita b le s u b s tit u te be found, a non -asbestos, non-fibrous g la ss f i l t e r of s u ffic ie n t pore siz e w ill be required downstream of the fib ro u s f i l t e r to remove the fib e r s of s iz e s su sp ected to be th e most hazardous. Only upon review and acceptance of submitted evidence that neith er of the above procedures r e su lts in a safe and e f f e c t i v e p a r e n te r a l drug or drug in g r e d ie n t w i l l th e FDA a llo w the continuation of present practices u tiliz in g these types of fibrous f ilt e r s . 2 b. Environments A ffected The primary environment to be a ffe c te d by t h is a c tio n w i l l be the environment o f humans r e c e iv in g p a ren tera l drugs. Secondary a f f e c t s o f t h is a c tio n w i l l be a lt e r a t io n s in the demands fo r a sb e sto s and n o n -a sb esto s f i l t e r s and the raw m a te r ia ls fo r the production o f th ese p rodu cts. 2. Probable Impact o f the A ction on the Environment a. Human Exposure The environment o f an organism can be d efin ed as a l l e x te r n a l substan ces and fo r c e s which impinge upon th at organism and thereby a f f e c t h is e x is t e n c e . Therefore, the environment of p a tien ts receiv in g parenteral drugs includes the m aterials in those particular drugs, including the a ctiv e ingredient, Lae s o lv e n t, s a l t s , b u ffe r in g a g e n ts, s t a b i l i z e r s , and im p u r itie s . This regu lation i s designed to elim in ate or minimize the fibrous im purities in th ese drugs, as there are in feren ces from in h a la tio n exposure to asb estos and from experim ents in lab oratory anim als which imply th a t th e p a ren tera l ad m in istra tio n of a sb e sto s in humans can cause f ib r o s is and tumors. A " s ta te of th e art" review o f th e hazards of exposure to a sb e sto s f ib e r s was w r itte n for the preamble of the proposed r e g u la tio n s and i s attach ed to t h is EIAR as Appendix I (General Background). The impact o f t h is a c tio n would be to minimize the human exposure to in je c te d a sb e sto s f ib e r s which may have a d e le te r io u s e f f e c t on both the d ir e c t ly exposed t is s u e s and r e sp ir a to r y t is s u e s subsequent to c ir c u la tio n . There i s no accep ta b le method o f e x tr a p o la tin g the p resen t data on experim ental anim als to man in a q u a n tita tiv e manner, but t h is r eg u la to ry a c tio n i s the 3 r e s u l t of a prudent analy sis of the r i s k s , b e n e fits and a n a ly tic a l techniques a s s o c ia te d with the i n h a l a t i o n , in g e stio n and p a r e n te r a l a d m in istra tio n of a s b e s t o s f i b e r s . The major en viro nme nta l e f f e c t w i l l be a r e d u c t i o n in exposure of humans to f i b r o g e n i c and tumorogenic m a t e r i a l s , and w i l l o n tr l b u te to an unquantd l i a b l e red u ctio n in incidence of these p a th o lo g ic a l occurrences. b . E f f e c t s on Raw M a t e r i a l s U t i l i z a t i o n The N a t i o n a l A s s o c i a t i o n of F i l t e r M a t e r i a l Man uf act ure rs has informed us t h a t a t l e a s t ten grades of f i l t e r s h e e ts or pads a r e provided by the asbestos f i l t e r in d u stry and th a t these f i l t e r s vary in asbestos content from 5-40%. The o t h e r b a s i c i n g r e d i e n t i s c e l l u l o s e wood pulp . Approximately 40 m i l l i o n p i e c e s of a s b e s t o s f i l t e r m a t e r i a l a r e produced an n u al l y of which 6 m i l l i o n p i e c e s go to p a r e n t e r a l o r i n j e c t a b l e drug p r o d u c e r s . These items are ty p ic a lly smaller than those provided to other users, such as commercial be ver ag e p r o d u c e r s , and t h e r e f o r e , an e s t i m a t e of 40 tons of a s b e s t o s and 80 tons of c e l l u l o s e wood pulp (of th e t o t a l 400 tons a s b e s t o s and 1,600 tons of c e l l u l o s e wood pulp used by the a s b e s t o s f i l t e r m a n u f a c t u r e r s ) a r e r e q u i r e d to produce the f i l t e r s which are subject to th is regulation. The 1973 Bureau of Mines M in er al s Yearbook l i s t s a p p a r e n t United S t a t = annual consumption of a s b e s t o s a t 876,147 t o n s . The EPA, i n correspondence accompanying t h e i r proposed standards fo r e fflu e n t guidelines f o r t h e p u l p , p a p e r and p a per boar d i n d u s t r i e s , has e s t i m a t e d t h a t about 50 m illion tons of pulp were produced in the United States in 1973. Therefore, the a s b e s t o s demand f o r p a r e n t e r a l f i l t e r p r o d u c t i o n i s 0.0045% o f t h e U. S. a s b e s t o s p r o d u c t i o n . The amount of c e l l u l o s e wood pulp r e q u i r e d f o r t h i s 4 production of the re g u la ted f i l t e r s is likewise i n s i g n i f i c a n t (0.00016% of U. S. p r o d u c t i o n ) . C e l l u l o s e a c e t a t e or n i t r a t e "membrane" f i l t e r s are the most l i k e l y s u b s t i t u t e s f o r a s b e s t o s f i l t e r s . Roughly 90 p e r c e n t of the U. S. p r o d u c t i o n of t h e s e p r o d u c t s i s done by M i l l i p o r e , In c . and by the Gelman Company. These firms have provided inform ation on t h e i r raw m a t e r i a l s u t i l i z a t i o n and estimated market sizes which demonstrates the insignificance of increases in demand f o r n a t u r a l r e s o u r c e s , even assuming complete s u b s t i t u t i o n of a s b e s t o s f i l t e r s by membranes. The e s t i m a t e s a re as fo l l o w s : At most, the r e g u l a t i o n s w i l l in c r e a s e the consumption of c e l l u l o s i c m a te ria ls by le ss than 130,000 lb s /y e a r . These m a te ria ls are derived from wood pulp (50 m i l l i o n tons produced i n th e U. S. in 1973) and a re p r o c e s s e d w it h a number of o r g a n i c s o l v e n t s (pe tro le um d e r i v a t i v e s , a l c o h o l s , k e t o n e s ) . The precise id entities of these solvents are confidential to these firms, but i t can be estimated th a t i f the re g u la tio n re s u lte d in the replacement of a l l s ix m i l l i o n a s b e s t o s f i l t e r s used a n n u a l l y , a maximum o f one m i l l i o n pounds of s o l v e n t s would be r e q u i r e d to produce the membrane s u b s t i t u t e s . The 1973 U. S. p r o d u c t i o n f i g u r e s on common s o l v e n t s have been p r o v id e d by the U. S. T a r i f f Commission ' ; f o ll o w s : Million lbs, producea Methanol 7,064 Benzene Million lbs, produced 28,000 Isopropanol Acetone 1,635 1,995 Cyclohexane 2,122 T h e r e f o r e , i n c r e a s e d demand f o r s o l v e n t s r e s u l t i n g from t h i s r e g u l a t i o n w i l l amount to f r a c t i o n s of p e r c e n t s , even i n t h e u n l i k e l y case of 100% c onv ersio n to c e l l u l o s e a c e t a t e f i l t e r s by the p a r e n t e r a l p ro d u c t i n d u s t r y . The a c t u a l conversion fig u r e s w i l l depend on the success of process m o d if ic a tio n s . 5 3 Pr oba b l e Adverse E f f e c t s Which Cannot be Avoided The adverse e f f e c t s of t h i s a c tio n which cannot be avoided are minimal. The p r o d u c t i o n of n o n - a s b e s t o s f i l t e r s w i l l of n e c e s s i t y i n c r e a s e . This w i l l r e s u l t in a s h i f t in raw m a t e r i a l s u t i l i z a t i o n from a sbestos to c e l l u l o s e . . .- b a s e d s o l v e n t s . The magnitude of t h e s e e f f e c t s was d i s c u s s e d in the previous section. 4. A lte rnativ es to the Proposed Action a . Different P.egulations (1) A ban on the use of a sb e s to s f i l t e r s i n the process of p a r e n t e r a l drug and drug in g re d ie n ts w ithout the phase-in period and without the allowances for the use of asbestos f i l t e r s with subsequent downstream f i l t r a t i o n , should the s c i e n t i f i c f i l t e r s s a c r i f i c e product q u a lity , would r e s u lt in the loss of a number of medically im portant p a r e n t e r a l l y a d m i n i s t r a t i v e m a t e r i a l s . Asbestos f i l t e r s a r e unique in t h e i r f i l t r a t i o n p r o p e r t i e s i n t h a t the f i b r o u s mesh can remove l a r g e p r o t e i n s and o t h e r pyrogens w ith o u t the r a p id d e c li n e in f i l t e r i n g capacity associated with conventional surface f i l t e r s . This "depth f i l t r a t i o n " has been r e s p o n s i b l e f o r th e s u c c e s s f u l p u r i f i c a t i o n of many blo od f r u c t i r --ion p r o d u c t s . I t i s n o t the i n t e n t of t h i s r e g u l a t i o n to remove a l l ->: . ` )s f i b e r s from p a r e n t e r a l d ru g s , no m a t t e r what t h e c o s t . The lo ss of a l i t e s a v i n g p a r e n t e r a l s due to d i f f i c u l t i e s in adapting non-asbestos f i l t e r s to the productio n scheme should be avoided. (2) A r e g u l a t i o n based on a sbe stos p a r t i c l e coun^ r a t h e r than process requirements i s not a v ia b le option a t th is time due to the u n c e r ta in t ie s 6 in p r e d ic tin g d ose-resp o n se w ith ca rcin o g en ic m a ter ia ls and due to d i f f i c u l t i e s in q u an tification methodologies presently associated with asbestos fib er cou n tin g. E lectro n m icroscopy fo r both q u a lit a t iv e and q u a n tita tiv e fib e r determ ination is a time-consuming, expensive technique requiring w e lltra in ed te c h n ic ia n s fo r both measurement and in t e r p r e ta tio n . Even th en , r e su lts are often cap riciou s. Thus, the lack of standard m ethodologies for a n a ly se s p reclu d es th e prom ulgation o f r e g u la tio n s based on fib e r count in the product, b. No A ction The "no action" a lte r n a tiv e would a llo w th e p resen t u se of a sb e sto s f i l t e r s in the manufacture o f p a r e n te r a l drug and drug in g r e d ie n ts to continue u n restricted . Although i t has been argued that asbestos fib er s are ubiquim us in the environment and th a t man has always been exposed to a background of a sb e sto s in h is a ir and w ater, we see a s ig n if ic a n t d iffe r e n c e between t h is n a tu ra l background and the p resence of a sb e sto s contam ination in m a te r ia ls adm inistered by subcutaneous, intravenous or intram uscular in je c tio n . These adm inistration routes circumvent the natural b arriers to in tern a l contamina tio n and have proven pathogenic and lab oratory animal s tu d ie s . T h erefore, t h is a lte r n a tiv e was r e je c te d fo r an a lte r n a tiv e which attem pts to minimize the p u b lic' s exposure to parenterally administered asb estos. 5. This action w ill not a ffe c t lo c a l, short-term use of the environment nor long-term p rod u ctivity as the magnitude o f resourse use i s n e g lig ib le in comparison w ith other in d u str ia l a c t iv it i e s . 7 6. I r r e v e r s ib le , ir r e t r ie v a b le commitment of n a tu ra l reso u rces r e s u lt in g from th is a ctio n w ill be n e g lig ib le due to the minor nature of the in d u str ie s a ffected , as discussed in section 2(b). 7. A ll known o b je c tio n s to t h is r e g u la tio n , as proposed, are d isc u sse d in the f i n a l r e g u la tio n i t s e l f . The reader i s refer re d to t h is document. 8. The C o st-B en efit C on sid eration s o f th ese A ction s are L iste d Below a. Costs The c o s t s to th e drug manufacturing in d u stry o f t h is r e g u la tio n w i l l not be p r o h ib itiv e . No comments on th e proposed r e g u la tio n from the drug ind ustry, d ir e c tly or through trade a sso c ia tio n s, claimed that the cost o f process m o d ifica tio n for p aren teral drug production would cause hardships. However, se v e r a l v o c ife r o u s communications from a sb e sto s f i l t e r manufacturers in d icate a fear of a sig n ifica n t lo ss in business, b. Benefits The b e n e fit from t h is a c tio n i s s o le l y in the human h e a lth area. The m in im ization o f p u b lic exposure to p a r e n te r a lly adm inistered a sb e sto s f ib e r s i s expected to have a p o s it iv e long-term e f f e c t on p u b lic h e a lth , as d isc u sse d in previou s s e c tio n s o f t h is EIAR. APPENDIX I GENERAL BACKGROUND "Asbestos" i s a g en eric term fo r a number o f hydrated s i l i c a t e s th a t, when crushed or p ro cessed , sep arate in to f l e x i b l e fib e r s made up o f f i b r i l s . Although th ere are many a sb e sto s m in era ls, only s ix are of commercial im portance. C h r y so tile , a tubular ser p e n tin e m in era l, accounts fo r 95 percent of the w orld 's produ ction. The o th e r s , a l l amphiboles (c r y s ta ls with three groups of metal io n s), are am osite, c r o c id o lite , an th op h yllite, tr e m o lite and a c t i n o l i t e . These a sb e sto s m in erals d if f e r in th e ir m e ta llic elem ental content, range of fib er diam eters, f le x ib ilit y , harshness, te n sile str e n g th , su rface p r o p e r tie s , and other a tt r ib u t e s th a t determ ine th e ir in d u s tr ia l u ses and which may a f f e c t th e ir r e s p ir a b i lit y , d e p o s itio n , r e te n tio n tr a n s lo c a tio n and b io lo g ic r e a c t iv it y (R ef. 1 ). Many products such as cement, f lo o r in g , s h in g le s , p ip e s , f i l t e r s , t e x t i l e s e tc . contain asb estos of one kind or another. There are great v a ria tio n s among such products w ith r e sp e c t to th e chances o f fib e r r e le a s e during the use of the product. The lik e lih o o d o f such fib e r r e le a s e depends predominantly on the ease w ith which the f ib e r s can be d islo d g ed and on the degree to which the use o f the product d estroys the fib e r s . Almost a l l a sb esto s fib e r used in the U nited S ta te s for m anufacturing products becomes t ig h t ly bound w ith in th e products and u s u a lly undergoes l i t t l e a c tu a l abrasion or wear b efore being discarded. A sbestos cement products (accounting for most of the a sb e sto s used in the United S t a t e s ) , s h in g le s and flo o r t i l e s are in t h is ca teg o ry . Some a sb e sto s -c o n ta in in g p rod u cts, such a s brake lin in g s , are sub je c te d to g rea t f r ic t io n ; th e ir r a te or wear i s c o n sid e r a b le , and a t tim es they are alm ost com pletely worn away. In th e ca se o f brake l in in g s , the a p p lic a tio n o f fo r c e i s so in te n se and the h ea t created so g rea t th a t most c h r y s o t ile fib e r s are destroyed by being converted in to another substance which i s n on -fib rou s. N e v e r th e le ss, an ap p reciab le percentage (1 to 3 p ercen t) remains a s fib ro u s a s b e s to s , and fib e r r e le a s e from products such as a sb e sto s c lo th , paper and sprayed firep roofin g m aterials is a seriou s source of em ission. This u sually occurs in densely populated areas. Host of the pipes d eliv erin g drinking water are o f a m ixture o f cement and a s b e s to s . Solid w astes produced during manufacture of a sb estos-con tain in g products, use o f such p rod u cts, and d em o litio n can be em issio n so u r ce s. These waste m aterials are usually disposed of without regard to th eir p o ten tia l as em ission sources. A lternate methods of d isp o sa l o ften r e s u lt in commingling o f a sb e sto s -c o n ta in in g w astes w ith m unicipal w astes in open dumps and thus create a long-term em ission source. A sb estos f ib e r s thus are u b iq u ito u s in a ir , water and a la rg e percentage o f th e e a r th 's c r u s t. The amount of t h is m a ter ia l which a d d itio n a lly i s added to the environment and to food and drugs by the use of a sb e sto s f i l t e r s i s not known. T herefore, i t i s obvious th a t the presence of a sb e sto s in th ese products is only one small source of exposure. A sb estos in h a la tio n has been known to be an o ccu p a tio n a l hazard in workers in a sb e sto s m ines. The a sb e sto s i s in h aled and lo d g es in th e lungs causing the development of a f ib r o t ic d is e a s e known as " a s b e s t o s is .' A sb e s to s is , or a b e s to tic pneum onoconiosis, was the f i r s t c le a r ly demonstrated adverse e f f e c t of a sb e sto s in man. I t i s c h a ra cterized by a p a ttern or roentgenographic changes in the lung co n sisten t with d iffu se in t e r s t it ia l fib r o s is of variable degree and a t tim es w ith f ib r o s is and c a l c i f i c a t i o n o f the pleura; c l i n i c a l changes th at in clu d e f in e r a le s , fin g e r clubbing and sh o rtn ess o f b rea th , each o f which may be absent in an in d iv id u a l ca se; and p h y sio lo g ic changes c o n sisten t w ith a r e s tr ic t iv e lung disorder (R efs. 2 through 8 ). In th ese workers in a sb e sto s m ines, m align an cies of the lung and of the body lin in g t i s s u e s , namely lung cancer and m esotheliom a, occur a t r a te s greater than in persons not so occu p ation ally exposed. There i s a 5 to 7 fo ld in crease in lung cancer in a sb esto s workers which i s noted as ea rly as 10 to 14 years a ft e r o n set o f exposure and i s s ig n if ic a n t a t 20 years (R efs. 9 through 1 5 ). Seven percent of deaths in a sb esto s workers are caused by p leu ra l and p e r ito n e a l mesothelioma (R efs. 16 through 3 3 ). This i s a marked in crea se sin c e t h is tumor i s extrem ely rare in the gen eral p o p u la tio n . There i s su g g e stiv e evidence concerning an in c r ea se in the r a te o f g a s t r o in t e s t in a l m alignancies in asbestos workers (Ref. 34). There i s co n sid era b le evidence that most human lungs harbor thousands or m illio n s o f a sb e sto s fib e r s although most people do not have a s b e s to s is (R efs. 35 through 3 7 ). This i s due to the u b iq u ity of the su b stan ce. Some o f th e se f ib e r s are c h r y s o t ile a s b e s to s , and amphiboles are probably presen t a ls o . This number o f f ib e r s i s r e la t iv e l y sm all in most persons not o c cu p a tio n a l! exposed to a sb e sto s compared w ith the numbers found in the o c cu p a tio n a lly exposed. The sy stem a tic a p p lic a tio n o f q u a n tita tiv e tech n iq u es, measuring both coated and uncoated f ib e r s , i s needed to d e fin e a g ra d ien t of accumulated f ib e r s fo r c o r r e c tio n w ith in cid en ce o f d is e a s e , on the one hand, and h is to r y o f environm ental exposure, on the oth er. The methodology fo r q u a n tific a tio n o f a sb e sto s f ib e r s o f varying s iz e s i s such th at the r e s u lt s obtained in one la b o ra to ry may vary s u b s ta n tia lly  from th ose in another. An in ter -a g e n c y governmental ta sk fo r c e to g eth er w ith other s c ie n t is t s working in th is f ie ld i s currently attem pting to develop standard technology which can be a p p lied to the id e n t if ic a t io n and q u a lif ic a tio n of a sb e sto s f ib e r s . The Environmental P r o te c tio n Agency i s c u r re n tly in v e s tig a tin g four sep arate tech n iq u es in order to e s t a b lis h the b e s t method fo r id e n t if ic a t io n , q u a n tif ic a t io n , s iz in g and typ ing of a sb e sto s p a r t ic le s and f ib e r s . At p r e se n t, the N a tio n a l I n s t it u t e fo r O ccupational S afety and _ H ealth (NIOSH) recommends, as a technique fo r sampling of a i r , a method based on counting f ib e r s greater than 5 microns in le n g th u sin g phase co n tra ct illu m in a tio n at 430x m a g n ifica tio n w ith a 4 m illim ete:r o b je c tiv e (R efs. 38 and 3 9 ). This technique i s c u r re n tly recommended fo r liq u id m a ter ia ls u n t il more accu rate and s e n s it iv e p r a c tic a l methods are developed. S im ila r ly , . ___ d i f f i c u l t i e s e x is t w ith other methods proposed for a n a ly sis of a sb esto s fib e r s in a m aterial such as ta lc . The evid en ce concerning the p o s s ib le hazard from in g e s tio n of a sb e sto s p a r t ic le s i s co n tr a d ic to r y and in c o n c lu siv e . In an unpublished study by L. M. Swinburn (R ef. 4 0 ), a s b e sto s p a r t ic le s were fed once a week to SPF Wistar r a ts fo r 16 and 18 weeks. The m a teria l was adm inistered in b u tte r . Although the p a r t ic le s were o f the s iz e range known to produce tumors by oth er modes o f a d m in istr a tio n , no tumorgenic e f f e c t was n oted . With a s in g le la r g e d o se, th e f ib e r s v?ere t o t a l l y clea red by the g a s t r o in t e s t in a l tr a c t in 48 hours and no a sb e sto s was d e te c ted in the animal t is s u e s a t the end o f 1 week. The g a s t r o in t e s t in a l ti'a ct o f the r a t seemed to provide an e f f e c t i v e b a r r ier to p e n e tr a tio n . #* In a pu blished study by W. E. Smith e t a l . (R ef. 4 1 ), ham sters m aintained on a d ie t of 1 percent c h r y s o t ile or am osite through l i f e had no g a s tr o in te s tin a l tumors. A rep ort by W estlake, Spjut and Smith (R ef. 42) in d ic a te s th a t th e r a t c o lo n ic mucosa i s p enetrated by c h r y s o t ile a f t e r feed in g a d ie t c o n ta in in g 5 percent asb estos for 3 months. Cunningham and P o n tefra ct (R ef. 43 and 44) in je c te d c h r y s o t ile f ib e r s 9 (9 .4 and 94 X 10 ) d ir e c t ly in to stomachs o f r a t s . F ib ers were found in blood and other organs 2-4 days a f t e r treatm ent. C ontrol r a t s , although having no a sb e sto s in b lood , a ls o had high l e v e l s o f a sb e sto s in t i s s u e s . These workers found th a t, whereas the tap water in Ottawa (having a f i l t e r plant) contained about 2 m illio n fib er s per l i t e r , the q u ality of fib ers in s o f t drink s and a lc o h o lic beverages purchased in the Ottawa area ranged from 1 to 12 m illio n f ib e r s per l i t e r . Even w ith the te c h n ic a l problems of m ethodology, t h is seems to in d ic a te th at in some beverages the a sb e sto s con ten t may be about th e same as in w ater, w hereas, in o th e r s , i t may be in crea sed . Thus, i t i s reason ab le to conclude th a t water and many other beverages for human consumption con tain s u b s ta n tia l amounts o f a sb e sto s f ib e r s . There i s some evidence th a t a sb e sto s f i l t e r s may remove some a sb e sto s m a te r ia l. In a p relim in ary experim ent performed by the Food and Drug A dm inistra tio n , a sb e sto s was added to d i s t i l l e d water and d isp ersed ev en ly by th e a c tio n of an u ltr a s o n ic gen erator. E lectro n m icroscopy of t h is m a ter ia l c le a r ly showed la r g e numbers o f a sb e sto s f ib e r s . This m a teria l was then f i l t e r e d through an a sb e sto s f i l t e r , and e le c tr o n m icroscopic exam ination o f th e f il t e r e d m a ter ia l showTed a red u ction in th e number of a sb e sto s f ib e r s . N icholson and h is c o lle a g u e s (R ef, 45) in v e s tig a te d a number o f samples o f p a ren tera l drugs and found a sb e sto s f ib e r s . Based on th e ir rep ort a study was undertaken by th e Food and Drug A dm inistration concerning contam ination of parenteral drugs with a sb esto s. Although the data are s t i l l prelim inary, the the follow in g observations are p ertin en t. P arenteral drug samples were c o lle c te d from a number o f firm s. Based on phase c o n tr a st m icroscopy, 11 o f 13 samples had c le a r -c u t evid en ce o f the presence o f a s b e s to s , one sample was q u estio n a b ly p o s it iv e , and one was n e g a tiv e . The number of f ib e r s ranged from 2 to 27 in the p o s it iv e specim ens of v a r ia b le sample s i z e . Using e le c tr o n m icroscopy, 12 of the 12 samples examined were p o s it iv e . Q u an titation i s not yet complete. In t h is survey, seven of 13 m anufacturers o f p a ren tera l drugs do not use a sb e sto s f i l t e r s ; four firm s use such f i l t e r s follow ed by f i n a l membrane type f i l t e r s (one of these uses asb estos f i l t e r s for i t s rin se water without f i n a l f i l t r a t i o n of such w ater); and two firm s use a sb e sto s f i l t e r s only for th eir rin se water, without fin a l filtr a tio n . The p relim in ary rep ort o f th e se s tu d ie s i s on d isp la y a t the O ffic e of th e Hearing C lerk. Any other s c i e n t i f i c data in t h is regard should be subm itted to the Hearing Clerk. C ertain p a ren tera l drugs, such as blood fr a c tio n a tio n p rod u cts, may be f i l t e r e d se v e r a l tim es through a sb e sto s f i l t e r s . Thus fa r , i t i s not known w ith c e r ta in ty whether th e more v is c o u s products could be s u c c e s s fu lly processed through term inal membrane f i l t e r s w ithout compromising s a f e t y , id e n t it y , str e n g th , q u a lity or p u r ity . The p r e c is e e f f e c t of a sb e sto s pad f i l t r a t i o n on removal o f pyrogens (R ef. 46 and 47) i s not co m p letely known a t th e p resen t tim e. C urren tly, the Food and Drug A dm inistration i s surveying the ind ustry for information concerning the use of asbestos f i l t e r s . R esults of th is survey w ill be incorporated in the public record. Although the major experim ental stu d ies of asb estos have involved in h ala tio n of fib e r s so as to sim ulate occupational exposure, several stu d ies have been performed to in v e stig a te the e f f e c t of parenteral in ocu lation of asbestos f ib e r s . In 1958, Schmahl (R ef. 48) reported th a t im p lan tation of a sb e sto s f ib e r s and crumbs in e ith e r th e subcutaneous t is s u e or in the peritoneum lead to the development of m alignant tumors (sarcomas) in 11 o f 30 r a ts which survived lon ger than 15 months a f t e r such im p la n ta tio n . Roe and h is c o lle a g u e s (R ef. 49, 50, 51) have performed a number o f s tu d ie s in which a sb e sto s f ib e r s were in jected subcutaneously (Ref. 49) in to the flan ks of m ice. In the f i r s t experim ents, c r o c id c lit c , am osite and c h r y s o t ile a sb e sto s fib e r s were used and each animal was in je c te d tw ice subcutaneously in both fla n k s w ith 10 m i l l i grams of f ib e r s in s a lin e w ith an in te r v a l o f f iv e weeks between th e in j e c t io n s . Seven of seven ty-on e mice which survived 40 weeks or more developed in j e c tio n s i t e tumors. In a d d itio n , one mouse developed a mesothelioma o f the peritoneum underlying the in j e c tio n s i t e . The in j e c tio n s i t e sarcomas were produced by a l l th ree typ es o f f ib e r s . In a d d itio n , Roe e t a l . (R ef. 49) showed th a t the a sb esto s fib e r s were w idely dissem inated from the lo c a l in je c tio n s i t e s being d ep o sited rath er s e l e c t i v e l y on the s e r o s a l su r fa c es o f the abdominal organs and the r e tr o p e r ito n e a l str u c tu r e s as w e ll as on the pericardium , diaphragm, pleura and adjacent p a rts o f th e lungs and h e a r t. These s e r o s a l su r fa c es reacted v ig o r o u sly to the presence of the a sb e sto s f ib e r s and in 10 o f 71 m ice, m alignant m esotheliom as of th e thorax and/or abdomen developed. In a la t e r study (R ef. 51) Kanazawa e t a l . showed th a t, a ft e r subcutaneous in j e c tio n of a sb estos fib e r s in m ice, fib e r s could be found to have dissem inated to r e g io n a l and d is ta n t lymph nodes, sp le e n , kidneys and o c c a s io n a lly to brain t is s u e su g g estin g th a t some a sb e sto s may en ter th e c ir c u la t io n . Thus, there i s experim ental evidence th at parenteral adm inistration of a sb e sto s f ib e r s may lead to wide d issem in a tio n o f such f ib e r s in anim als and to the development of lo c a l m alignant tumors a s w e ll as m alignant m esotheliom as o f th e pleura and peritoneum sim ila r to th o se th a t occur a ft e r ' inhalation of asbestos fib ers. The problem o f a sb e sto s in the t o t a l environm ent, to which th e worldwide s c i e n t i f i c community i s ad d ressin g i t s e l f , i s very complex. The Environmental P r o te c tio n Agency has published in the F ederal R e g ister of A p ril 6, 1973 (38 FR 8820) n a tio n a l em ission standards fo r a sb e sto s m illin g and manufacturing based on the determ ination th at a sb e sto s i s a hazardous a ir p o llu ta n t. This standard has been developed d e s p ite the f a c t the EPA a ls o rec o g n iz e s th at a "standardized r e fe r e n c e method has not been developed to q u a n tita tiv e ly determine the content of asbestos in a m aterial." The present s ta tu s o f t h is problem i s summarized by the rep ort of a committee prepared subsequent to a meeting sponsored by the In tern a tio n a l Agency for Research on Cancer (Ref. 5 2 ). The Food and Drug A d m in istra tio n 's review of th is report ind icates the follow ing areas of further research are necessary: (1) Further epidemiology, p a rticu la rly with respect to past exposure to a sb e sto s and cancer of s i t e s other than lu n g , p le u r a , and peritoneum . (a) Assessment of excess cancer r isk s follow in g exposure to only one type of fib er . (b) In v estig a tio n of whether reduction of a sb esto s exposure in lungs below those causing a sb e sto sis ab olish es excess r isk of carcinoma. 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H e a l t h , 58_: 1658-1666, 1968. 34. Wagner, J . C . , "Epidemiology of D iffuse M esothelial Tumors: Evidence of an A ssociation from Studies in South A frica and the United . Kingdom.," Ann. N.Y. Acad. Sci . , 1 3 2 :5 7 5 -5 7 8 , 1965. 3 5 . Churg, J . , E.C. Hammond, A.M, L a nge s, K . J . N i c h o l s o n , L . J . S e l i k o f f and Y. S u zu k i, " B io lo g ic a l E f f e c t s o f A sb e sto s," presented at the N ational In stitu te s o f H ealth, Feb. 1, 1973. 3 6 . A n v ilv e l, L. and VMM. T hurlbeck, "The In cid en ce o f A sb esto s B odies in th e Lungs a t Random K ecro sp sies in M ontreal," Can. Med. A ssoc. J . , 95:1 179-1 182, 1966. 37. Cauna, D . , R.S. T o t t e n and P. G r o s s , " A sb e s to s Bodies i n Human Lungs a t A u t o p s y , " JAMA, 1 2 :371-373, 1965. 38. " C r i t e r i a f o r a Recommended S t a n d a r d - O c c u p a t i o n a l Exposure t o A s b e s t o s , " Rep or t o f Rev lev.' Committee, N a t i o n a l I n s t i t u t e f o r O c c u p a t i o n a l S a f e t y and H e a l t h , P u b l i c a t i o n No. HSM 7^-1^267 (197 2) . 39. Lynch, J.R . and H.E. Ayer, "Measurement of Asbestos Exposure," J . Occup. Med. . 1 0 :2 1 - 2 4 , 1968. 40. Swinburne, L.M., "The i n g e s t io n of asbestos by r a t s (unpublished d a t a ) , " p e r s o n a l communication t o Bureau o f F oods , FDA. 4 1. S m i t h , hT. E . , L. M i l l e r , R.E. E l s a s s e r and D.D. H u b e r t , " T e s t s f o r C a r c i n o g e n i c i t y o f A s b e s t o s , " Ann. N.Y. Acad, S c i . . 1 3 2 : 4 5 6 - 4 8 8 , 196 4 2 . W e s t l a k e , G . E . , , H . J . S p j u t and M.N. Sm i th , " P e n e t r a t i o n o f C o lo n ic Mucosa by A s b e s t o s P a r t i c l e s . An E l e c t r o n M i c r o s c o p i c Study in Rats Fed Asbestos D ust," Lab. I n v e s t . , 14:2029-2033, 1965. 43- Cunningham, H.M. and R. P o n t e f r a c t : (a) "Asbestos Fibers in Beverages and Drinking Water," N ature, 232:332-333, 1971. (b) "Symposium on I n d u s t r i a l Chemicals as Food Contam inants," J o u r n a l o f t h e AOAC, 5 6 :9 7 6 - 9 8 1 , L973- 4 4 . P o n t e f r a c t , R. and H.M. Cunningham: "Penetration of Asbestos through the Digestive Tract of Rats," N ature, 24: 352-353, 1973. 45. Nicholson, W .J., C.J. Maggiare and I . J . S e lik o ff, "Asbestos Contamination of P a re n te ra l Drugs, Sci cnee, 177:171-173, 1972. 4 6. T u i , C. and A.M. W r i g h t , "The P e n e t r a t i o n o f Non-Pyrogen I n f u s i o n and Other Intravenous Fluids by Absorptive F i l t r a t i o n , " Annals Surg., n_6:412-425, 1942. 47. Remington's Pharmaceutical Sciences, "Parenteral Preparations, Pyrogens," Chapter 82, 14th Ed., (pg. 1524), 1970. 4 8 . Schir.ahl, D. , "Cancerogene Wirkung von A s b e s t b e i I m p l a n t a t i o n von R a t te Zei f s c h r i f t f u r Krebs f o r s c h u n a , 62_: 561-567, 1958. 49. H arington, J .S , and F .J .C . Roc, "Studies of Carcinogenesis of A s b e s t o s F i b e r s and t h e i r N a t u r a l F i b e r s , " Annals o f t h e N,Y, Academy o f S c i e n c e s , 1 2 -.439-450, 1965. 50. Roe, F . J . C . , R.L. C a r t e r , M.A. W a l t e r s and J . S . H a r i n g t o n , "The P ath o lo g ic a l E ffe c ts of Subcutaneous I n j e c t i o n s of Asbestos F ib e rs in Mice: M igration of F ib e rs to Submeso- t h e l i a l Tissues and Induction of Mesotheliomata," I n t . J . of Cancer, 6 2 8 -6 3 8 , 1967.  51. Kanazawa, K ., M.S.C. Birbeck, R.L. C arter and F .J .C . Roe, "Migration of Asbestos Fibres from Subcutaneous In je c tio n S ite s in Mice," B r itis h Journal of Cancer, 24:96-106, 1970. 52. "Report of the Advisory Committee on Asbestos Cancers to the D i r e c t o r of the I n t e r n a t i o n a l Agency f o r Research on C ancer," B r i t . J . I n d u s t r , Tied. . 3 0 : 1 8 0 - 1 8 6 , 1973. \ MQRANDU# DEPARTMENT OF HEALT UCATION, AND WELFARE PU B L IC H E A L T H SE R V IC E FO O D A N D D R U G A D M IN IST R A T IO N t o : Dr. Christopher 0. Schonwalder O ffice o f Environmental Q u a lity , FDA HFS-30 d a t e : June 2 1 , 1974 f r o m : P h ilip P. McGrath, E lectron M icroscope Branch D iv isio n o f P ath ology, Bureau o f B io lo g ie s , FDA - HFB-400 s u b j e c t : A sbestos f ib e r s in f i l t e r e d , d eio n ized w ater a f t e r passage through an asb estos f i l t e r pad In response to your telephone request o f June 6, 1974 fo r inform ation concerning the r elea se of asbestos fib e r s or f ib r i ls by asbestos f i l t e r pads during the f i l t e r i n g p r o c e ss, we performed the fo llo w in g t e s t : membrane f i l t e r e d d eion ized w ater was f i l t e r e d through an a sb esto s f i l t e r pad housed in a m etal f i l t e r h o ld er, see attached p ro to c o l. Examination of the f ilt r a t e in the transm ission electron microscope revealed fib ers and f i b r i l s o f varying s iz e s in 7 o f 20 grid squares on one carbon coated grid con tain in g a 5 m ic r o lite r drop o f the f i l t r a t e . Figures 1 and 2. A second grid examined had a s im ila r d is tr ib u tio n o f a sb esto s f ib e r s . Exam in a tio n o f f i l t e r e d d eio n ized w ater on carbon coated grids showed no a sb estos fib ers. P h ilip P. McGrath 1. 3000 m i l l i l i t e r s o f f i l t e r e d d eio n ized w ater was f i l t e r e d through a M illip o r e membrane f i l t e r w ith a pore s iz e o f 0 .2 m icrons. The fla s k used to r e c e iv e the f i l t e r e d w ater was r in sed w ith f i l t e r e d , deionized water. 2. A m etal S e itz f i l t e r h old er from the R epublic S e itz F i lt e r Company was c a r e fu lly r in sed w ith f i l t e r e d d eio n ized w ater and a D-10 S t e r if lo a sb esto s f i l t e r pad from F. R. Harmon and Co., M illd a le , Conn, was clamped in the m etal S e itz f i l t e r h o ld er. 3. F ifty m i l l i l i t e r s o f f i l t e r e d d eion ized water was f i l t e r e d through an a sb e sto s pad in the m etal h old er u sin g house vacuum a t a n eg a tiv e pressure of twenty to tw en ty -fiv e inches o f mercury. This f i r s t f i l t r a t e was d iscard ed . 4. Ten more m i l l i l i t e r s o f f i l t e r e d d eio n ized water was f i l t e r e d through the same a sb esto s f i l t e r pad u sin g house vacuum at a n e g a tiv e pressure o f 20 to 25 inches o f mercury. The w ater was f i l t e r e d in to a 700 m i l l i l i t e r erlenmeyer fla sk which had been rin sed w ith f ilt e r e d , deionized water to reduce p o ssib le contamination with background asbestos fib ers. 5. Five m ic r o lite r drops of the f i l t r a t e were placed d ir e c tly on carbon film supported on a 300 mesh copper e le c tr o n microscope g rid s and examined in the e lec tr o n microscope. 6. Two grid s were examined. In one g r id , 7 o f 20 grid squares examined contained c r y s o t ile a sb esto s f ib e r s . The second grid had a s im ila r d is tr ib u tio n o f f ib e r s . Figures 1 and 2 are r ep re se n ta tiv e photo graphs of the fib ers seen in the f ir s t grid. 7. Carbon film grids or carbon film grids co n ta in in g f iv e m ic r o lite r drops o f f i l t e r e d , d eio n ized w ater were examined as c o n tr o ls . No asbestos fib ers were seen in these con trols. Figure 2 Crysotile asbestos fiber particles introduced into filtered distilled water during passage through an as bestos filter pad. Magnification: 68,000