Document 0J9dGxVw0o9yo46D2L46Ozz4V

FILE NAME: US Gypsum (USG) DATE: May 5, 1936 DOC#: USG060 DOCUMENT DESCRIPTION: 1936 Letter to Owens Illinois Glass Company re report on biological activity of glass wool. r ' ^ > / ' May '5 , . i 1936 A n , ft/// Ui ' V . i w * Owens I l l i n o i s G la s s Comoany T o led o , Ohio A tte n tio n : r . V/.G.Hazard Gentlemen : I su b n it the fo llo w in g r e p o r t o f an in v e s t ig a t io n o f the b io lo g ic a l a c t i v i t y o f g lass*w o o l undertaken a t your request in the Saranac Laboratory. To determ ine w hether p a r t i c l e s o f g la s s wool sre capable o f producing re a ctio n iiv the t is s u e s , suspensions o f f in e l y ground plain^and o ile d wools were in je c te d in to the ear veins o f r a b b it3 and the p e rito n ea l c a v itie s of guinea p ig s . Experience in th is la b o ra to ry and elsewhere has dem onstrated th a t these methods are adequate to demonstrate the ca p a city o f a m ineral dust to produce fib r o s i s . In v e s t i g a tio n o f over 20 d iffe r e n t ty p e s o f d u st has In d ica te d th at i f no r e a c tio n occu rs in organs o th e r than the lu n g s , i t w i l l not occur in the r e sp ir a to r y tr a c t and th a t conversely dusts lik e s i l i c a and asb esto s t h a t are known'to produce fib r o s is o f the lu n gs a ls o cause f i b r o s i s in o th e r t is s u e s when I n je c t e d in s u f f ic ie n t q u a n t it ie s . Neith e r p la in or o ile d g la ss wools have caused fib r o s is or any `chronic progre ssiv e reaction~by i n j e c t ! o n and t h e r e fo r e i t i s a reason^b.ue o scu n o tio n t h a t th e ir in h a la tio n would lik e w ise fa ll*~ to produce such e f f e c t s . .G l a s s w ool c s h n c t .b e . c l a s s i f i e d as an in e r t dust f o r ^ alth o u g h i t causes no p r o g r e s s iv e f i b r o s i s n e v e r th e le s s i n j e c t i o n o f la r g e amounts in to the p e r ito n e a l c a v i t y o f the mainea p ig u s u a ll y produces innrcdlato d e a th . A p p a ren tly t h i s is due to the presence o f sodium s i l i c a t e which has a s im ila r a c tio n . Anim als s u r v iv in g t h i s immediate e f f e c t develop no ch ro n ic changes. This actio n of the g la ss could h ard ly occur in the lu n g3 o f a person in h a lin g i t because the concentration could never be g r e a t enough to produce such an e f f e c t . , od o To d e term in e w h e th e r th e i n g e s t i o n o f g l a s s wool p a r t i c l e s is capable o f i n j u r i n g the stomach an: i n t e s t i n e s r u l n e a o ig s were f e d 2 . 5 c c . o f a 20 c o r c e n t s c n s i on o f OOy o g l a s s c a r t i d e s m ixed w dh. * h e i r g r a i n 6 days ./eek, e v e r a t3 I lb page 2 period from 4 to 1 7 'weeks, w ith proper precautions th a t a l l o f the m a te r ia l was consumed. A n oth er group r e c e iv e d two doses t o t a l i n g from 0.575 to 0.8 gm. o f g la s s p a r t i c l e s , in w ater s u s p e n s io n , by stomach tube b e fo re the morning fe e d in g s . Then th e *a n im a ls were k i l l e d , 4 to 17 weeks l a t e r , no tr a c e o f the g la s s or in ju r y produced by i t co u ld be d isco vered in any part p f the alim entary t r a c t .. Therefore l.t is concluded that the in g e s tio n o f even e x ce ssiv e q u a n t i t i e s of g la s s wool p a r tic le s 100 m icrons or le s s in d ia m e te r , procuees no i n j u r y * The d e t a i l s o f th e se v a r io u s experim ents are summarised as fo llo w s: Preparation of dusts B oth p la in wool and o i l e d g la s s wool c o n ta in in g 11 f0 o i l were crushed in an agate m ortar ana then ground w ith w ater in a p o r c e la in b a l l m i l l fo r 432 h o u r s . I t was then n e a r ly d r y ; more w ater was added and th e m i l l i n g was co n tin u ed fo r an oth er "` 408 h o u r s . The m a te r ia l removed from the m i ll was p la ce d ir. a *' la r g e beaker and allo w e d to sta n d over n ig h t . Exam ination of the supernatant f l u i d showed a h ig h co n ce n tra tio n o f p a r t ic le s 1 to 3 m icrons in d ia m e te r . '.7ith the o i l e d g la s s some o f th e o i l had sep arated in the p ro ce ss o f g r in d in g and t h i s had to be d iscard ed but exam ination showed co n sid e ra b le o i l in the su sp en sio n t h a t was s u b se q u e n tly p rep ared . The c o n c e n tr a tio n was a d ju s te d w ith v/ater to 1 and s u f f i c i e n t sodium c h lo r id e was added to make th e su sp en sion iso to m ic w ith the body f l u i d s . Intravenous in je c tio n s . a) P la in g la s s wool - 4 r a b b it s r e c e iv e d 1 gram o f 1 to 3 m icron p a r t i c l e s ir. 20 i n j e c t i o n s o f 5 cc e a ch , adm inistered bi-w eekly. R a b b it frl4 d ie d , p ro b a b ly o f c e r e b r a l embolism, .on th e day- fo llo w in g the la s.t i n j e c t i o n . Such a c c id e n ts are' not' uncommon in t h i s ty p e o f I n j e c t i o n . Autopsy showed no g r o s s evid e n ce o f d is e a s e . In m icro sco p ic se ctio n s, c o lle c tio n s o f dust containing phagocytes were found in the lu n g s , sp leen and l i v e r . F re q u e n tly th e se c e l l s were o f th e g ia n t v a r ie t y and they co n ta in e d 'm asses o f g la s s fr a g m e n ts . There was no evidence o f inflam m atory change about them. Gf0.?l 0994 R ab b it y 13 was k i l l e d 15 days a f t e r c c r r le t ir .g the i n j e c t i o n s . There were n o -gro ss chances end the m icroscope repealed i d e n t ic a l r e a ctio n s tc those ir. fl4 > except th a t dust c e lls rov occurred in the lymph node d r a in in g the l i v e r . o "/e <3 ? ***^3 "LSR was no d i f f e r e n t from chr.t ir. 13 r"''p nic *; page 3 Rabbit #11 was k illa c i a f t e r 259 d ays. Thera was a b so lu te ly no gross evidence o f re a ctio n t o ,d u s t . M icroscop ic se c tio n s have not y et been made as the animal was not k i l le d u n t i l y este rd a y. b). O ile d g la s s wool - 4 r a b b its re ce iv e d 1 gm. of 1 tc 3 _ micron p a r t ic le s in 20 In je c tio n s o f 5 c c . each, administered .bi-w eekly. . Rabbit #1 was k i l l e d 143 days a f t e r com pleting the in je c t io n s . There were no gross changes and the microscope revealed a reaction ind istin gu ish ab le from that in rab b it #13. Rabbit #2 was k i l l e d a f t e r 181 days - the p ictu re was the same. Rabbit #3 was k i l le d a f t e r 285 d a ys. Like #1, the animal showed a b s o lu te ly no gross evidence o f d is e a s e . M icroscopic examination w ill not be completed in time to be included in th is re p o rt. Rabbit #4 i s s t i l l a l i v e and ap paren tly w e ll. I t w i l l be allow ed to li v e fo r one year but there is no reason to su sp ect th a t i t w i l l develop fu rth e r r e a ctio n . These r e s u lts are in every way comparable to those observed with in e rt d u s ts , aluminum o x id e , fe ld s p a r , flu o rsp cr and 3 types o f s e r i c i t e have a l l shows s im ila r r e a c tio n s . Uncor.bined s i l i c a , on the oth er hand, produces acute inflammations follow ed by p rogressive f ib r o s is in the various organs. The li v e r shows a massive f ib r o s is that reduces the organ to a d is to r te d mass of sca r and the spleen is enlarged and studded with nodules. No microscope is n ecessary to a isco v e r the r e s u lt s o f the in je c tio n s which begin, to be m anifested before a ll the s i l i c a ha3 been in je c te d . Intraperitoneal injections ' a) P la in V/ool Four guinea p ig s were i n j e c t e d i n t o the p e r ito n e a l c a v i t y v/ith 2 cc a 10/ suspension o f the 1 to 3 micron p a r tic le s described above. Cr. the fo l lo w i n g morning two were deed. Their abdomens were d is te n d e d snd on opening then the p e r i t o n e a l s u r f a c e s were i n f larr:V.ec. p a r t i c u l a r l y in the r e g i o n of d e p o s i t s of the g l a s s o u s t th a t were s c a t t e r e d here and th ere over the d i f f e r e n t o rgans. The sm all in t e s t i n e wps of le f-r.-i d i l c ted with The experiment ,.os r e o e a te d and again 3 c f 4 animals were dead w i t h i n 24 h o u r s , sh o ein g s im il a r r e a c t i o n . **he th ree anim als th a t su r v iv e d at f i r s t snowed . 'T.-.Y`r. >peve<*. v-r **& *& #& Cf>021 0995 page 4 abdominal d is te n tio n but th is disappeared w ith in a week. They were k i l l e d la t e r w h ile ap p aren tly w e ll. 1 8 , k i l l e d a f t e r 23 w eeks, showed 3 minute g re y -w h ite p a tch e s on the s u r fa c e o f th e peritoneum th a t the m icroscope revealed to be clumps o f phagocytes coh- - t a in in g . p a r t i c l e s o f d u s t* There was no f i b r o s i s . #6 and 8, k i l l e d a f t e r 34 w eeks, show'ed r.o g ro ss evidence of reaction but in'm icroscopic section s a few compact c o lle c tio n s o f du st c e ll s could be found on th e s u r fa c e o f the omentum. b) QUed Wool Four gu inea p ig s were i n je c te d in to the p e r ito n e a l c a v i t y w ith 2 c c , o f a 10% su sp en sion o f the 1 to 5 m icron o i l e d g la s s p a r t i c l e s d e s c r ib e d ab ove. On th e fo llo w in g morning a l l were dead w ith the same evid en ces o f an a cu te p o iso n in g d e scrib e d in the p la in g la s s group. The t e s t was re p e ated on 4 more guin ea p i g s . This time o n ly one an im al was dead th e n ext day but an oth er d ie d on th e t h i r d day and the o th e r two on the fo u r th . A l l showed the sans evidences of acute poisoning in the peritoneal c a v ity . To c o n tr o l t h i s e x p e rie n ce two guinea p ig s were i n j e c t e d i n t r a p e r i t o n e a ll y w ith ~ th e same q u a n t it y o f f i n e l y powdered sodiiim s i l i c a t e . They lik e w is e died w ith in 24 hours and e x h ib it e d the seme type o f r e a ctio n in the p e rito n eal c a v ity . Unpublished data from another la b o ra to ry corrob orates th is e f f e c t o f in tr a p e r ito n e a l in je c tio n of sodium s i l i c a t e . T h is r e a c tio n is- unusual and has not beer, observed a f t e r the in je c t io n of. .other typ es o f d u st which inclu d e a v a r ie ty o f s i l i c a t e s ; Furthermore the in tr o d u c tio n o f a sm aller dose o f pur3 sodium s i l i c a t e d i r e c t l y in to the lu n gs has not produced t h is r e s u l t . In 1923 a g r o u p .o f 15 guinea p ig s was given i n t r a t r a c h e a l i n j e c t i o n s t o t a l i n g 13 rr.grns. o f sodium s i l i c a t e and none o f then showed any adverse symptoms. The c o n d itio n s in t h is experim ent were d i f f e r e n t from those in the p resen t one as the dose was d iv id ed and adm inistered in 7 in je c tio n s djrir.g a period o f approxira t e l ,T a month. No a n im a l r e c e iv e d more th a n 2 r.gms. = t any one tim e . Ha-werthe l e s s , i t seems not u n lik e ly th a t i f vh is s i l i c a t e -.vere u n iso n o u s when ad m in istered ck r e c ti'* i n t o the ] unrs seme o f the an im al9 might have shown '~ .s ` ar.s. C o r s a ir !'.' i t con be conclude i th e ; a human h e i r .- 'o u ' d v,ot be l i k e ] ' * to in h a le to x ic q u a n tity o f sodium .s ilio a t e in ohe form o f g la s s wool d u s t. < s ^ ao o - r- 1 * .waM i PS3 5 13 In r ss tlo r . Experim ent These t e s t s were perform ed w ith p la in g la s s wool o n ly as previous t e s t s had in d ica te d th a t the o ile d m aterial did not a c t'd iffe re n tly . Pour f a s t in g gu in ea p ig s were in je c te d by stomach tube w ith -fr o m 1 . 5 -to .6 ccT o f a. 5% suspension - o f g l a s s wool ground in a m o rtar so t h a t th e p a r t i c l e s were 100 m icrons and l e s s i n d ia m e te r . None shewed any i l l e f f e c t s so the i n j e c t i o n s wore r e p e a te d a f t e r S3 d a y s . T h is tim e d o ses o f 2 and 5 cc o f a 101 s u s p e n s io n were em ployed and a g a in th e r e were no symptoms. The t o t a l doses fo r the 4 anim als were as fo llo w s : # 4 . . . . 1 .5 cc (575 mgm) #3. 4 cc (700 mgm) 1 . . . . 2 .0 cc (600 mgm) (Note th a t these t o t a ,l s were , p relim in ary statomor.t o f Ja n . f/2. 26, 6 cc (300 mgm) v r`,enc" "c 1 in. the Since there was no,, appareAnntt r e. a c t i o n t- o of *these the -fl inje pc .ec ^* y ction us in e s , i t was decided to continue tne r>. g r a in fe d to the a 20,1 asnu ssupeern,ssioonn mmined wv :itnh a ^ an im als b e f-o r e th e y were si*v>reenn " ^ C Ct Cn,e~ru*loRforra mlorrnuiriu.=g* rr aa ttiioonn f^eodd QoT~5 g- "n. .o f .# Thesce. g l a sssr, 4 p'ir.ca p ig s and 5 o th e r enss^w w* ^ o*;a ffoo lliioo vv..iirr._rr tta bc lies ssiu^nnnissrr iii. 6 days a week u n t i l th e y were ki.Lj.ed th e ir treatm ent; A n im al No. 2 3 To. 4 5 rf i . 6o 9 O lacs hy i s c h Tube l 3t F e e d in g -2 n d F e e d in g - nw Oo w t 0.1 0 .0 7 3 " t u O*** * 0.F ca . 0 .3 " 0 .5 " i.'.c-a w i t h Food 1 3 .2 2 6 .5 26.5 39.5 13.63 6 .3 3 9 .5 31.0 C?- * n it ri it f it t ir T o t a l 10^ 1 3 .9 2 7 .2 w lt 27.1 ff 40.75 ft 1 3 .0 (f . 2 6 .5 II 3 9 .5 ff 5 1 .0 tf tf 5 1 .0 If ic r . ne 32 C i. Sc 94. 30 61 32 119 112 IIP 3 - "-- ff * If ft If It ft tl 1 ft r** Vs i,1 T1 ; Vyu ^ * L " : Z e s ~ i m l t r a c z b fsl O IvVSu,.-' page 6 r One may th erefore conclude th at the In gestion o f ss much as 51 grans o f f i n e l y pcv.serad gi&gg wool, a d m i n i s t e r e d in d ivid ed d o se s, w i l l n et cause in ju r y in 4 months t i n e . In the absence of any r e a c tio n a t a l l i t would h srd lv seem e s s e n t ia l to continue the in vestigatio n fu rth er. " * The general co n clu sio n th a t both o ile d and p la in g la s s wools are incapable o f e x c itin g progressive fib r o s is in the t is s u e s I s warranted from these observations in view of the wide experience in t h is la b o rato ry w ith these methods o f t e s t in g the b io lo g ica l a c tiv ity o f Inorganic dusts. T ru stin g th a t these fin d in g s may a lla y any s ce p ticism as to a th e o r e tic a l hazard involved from the handling o f g la s s v/ool, I am Very tru ly yours, LUG:CC Leroy U. Gardner, tl.D. D ire cto r Rabbit #3 - k i l l e d a f t e r 365 days " #4 - " . " 285 " They showed no fu r th e r change. (*'*02 i 0998 i'f*. f v.Y.d"!