Document 71qeBvp5KEd67x4jmZMYeLR2R

U llK VS6X * OAO0 9>t00 3 *V-> ::?;:'-- `V , fi > K- A dgp. Og majppxifi.m-fiif a a p TjgaAJgmu: v t* A* H ldridge ,1 -V4*J r*i -, .** 'i ' ' 4"T$ I ,.,.. x? JCTlQtfi . *> * n ,' ' ,,-Vi s*1'-* The o b ject o f the follow ing t e s t a was to determine the * to x ic ity o f Lead T otrn th y l upon animal s and to study the symptoms produced toy t h is ooopoond* your d iffe re n t methods ware used to X ' X adm inister tho eotapound and l e t h a l p o in ts war e sta b lis h e d by each ` - X method* The methods employed were a s follow s lo c a l app licatio n 'l subcutaneous Injection intravenous injection- and inhalation* I I . . tKOUAU, - 1* The l th a l p o in t by SStia a p p lic a tio n vus plaeed u t 0*6 c e . o r 0.99 gnsa p e r k ilo fo r euiuoa pig* and e t 0 .3 o e. or 3.498 gram p e r fcilo fo r dogs* 1 co . o f pure Lead T etra JBthyl vrelghs 1.889 gras. : 2 . The le th a l p o in t fo r guinea p ig s by subcutaneous in je c tio n i s sj;proxijaatoly 0.08 a c . or 0.132 grosz p e r h i l e . 3* 71te l e th a l point fo r dogs by intravenous in je o tio n i s placed a t 0.011 o c. o r 0*018 gram p a r k ilo . 4* Tho le th a l co n cen tratio n fo r doe by in h alatio n i s placed a t 5.11 m illigram s per l i t e r * 6* : The evidenoe indicuta* th a t sm aller doses a re cumu la tiv e in a c tio n by whatovor route adm inistered. , ` 8* M;an an an in a l re c e iv e s a le th a l dose by tin a p p lication i t s l i f e nay be saved by washing v i t a kerosene followed by tin c tu re green soap and water provided th is treatm ent i s c a rrie d out w ithin th irty minutes a fte r application. * XTj'P-'?* I i &mX KM 0 0 1 7 7 , ,, $ ';-v< l'*25#3?'.N *. j ' * f-'/i Uh um m & l T v ,v . t i u m l t 1m & polwtsiBg i f th e sssmoiiest o f * u . `^ f b n s o f e ts ll l o p o leonln c > t w m u te le a d poisoning, th a t i s the o ffset o f a sadden absorption o f loud in non hue toon h ith e rto unknown* Whoa a la rg e q u a n tity o f m b * soluble Bolt o f loud lo sh allow ed,it gives r i s e to the ordinary syarptoms o f i r r i t a n t poisoning namely, nausea, Totaltin g , p a in in th e abdomen, vio le n t purging, weakness am co llap se. ' p. v In animals a lso , i t has been d iffic u lt h ith e rto to pro dose acute le a d poisoning beoause when a o st forms o f lea d a re in je c te d the p ro te in s o f th e blood a re p re o lp lta to d and death eo prodaeed i e purely m echanical, a m only lo c a l symptom* ware p ro daeed by a d m in istratio n by mouth* However Harnack in je c te d s a l t s o f lead trie th y l* In the frog th is produced general paralysis apparently by ths a c tio n o f lead on the c o n tro l nervous system* In th e dog the symptom# follow ing intravenous in je c tio n wore > weakness end p a ra ly sis, v io len t diarrhoea and o o lio , ohoreu-llfce movements, trem ors, and convulsions* She diarrhoea was found to be doe to v io le n t c o n tra c tio n s o f the in te s t i n a l n u lls , which m aintained a degree o f c o n tra c tio n even whan no p e r i s t a l t i c wave was passing* (Guahny - Pharmacology and T herapeutics, page i&3*) ,JVv ~s " ' le a d t e t r a e th y l was developed by the Gonoral liotors and Du Pont eorporu t io n s a s an a d d itio n to motor fuels* hut soon a f t e r la rg o sonla production was coteuenood, a number o f toon handling t h i s product boourns i l l and sev eral o f them died* She follow ing da s c rip t ion o f the symptoms was included in a rep o rt to the standard o i l Gocgsuaiy by Prs* Thomson and Gehoenleber, rendered hay 10, 1924* , r "The f i r s t symptoms observed a re a marked f u ll in blood p ro ssure sometimes a s lew a s six ty p o in ts below normal* Share i s an acoespanylng f u ll in body temperature which has been recorded as low a s 94*6 degrees Fahrenheit or four degrees below normal* She h e a rt a c tio n i s slowed, the pulse havlug dropped in one ease a s low a s 40, th a t i s , twelve or more oounts below normal* Shore i s a t f i r s t some d ig e s tiv e disturbance, such a s lo se o f a p p e tite , vom iting and a tendency to looseness o f the bowels* V ertigo may be present* The red blood corpuscles show marked changes in s is e and shape* The blood in one o f the fU tul oases ffeilea e n tir e ly to ' i>-,,* -a- eoa& ilate and a t autopsy showed an unusual c o lo r such a s i s ob- \ served in earbon aonoxido poisoning* m e re i s no cyanosis and _ no shortness o f b re a th , nor la headache o r o th er pain eoqplalned of* She u rin e remains normal u su ally b a t in one ease rep o rted treated by Dr. xt Of Harvard le a d was p resen t In It* follow ing these sycg>toms in severe eases o th e r phenomena appear in d ic a tiv e o f profound eerebral disturbance* She vie t i n su ffe rs fire* p e r s is t eat Insomnia and beeonas d elu sio n al, e x tra o rd in a rily r e s t less and talkative* H is g a it i s staggering lik e th a t o f a drunken Ban, but th ere ia no p a ra ly s is and convulsions do not appear* Share i a exaggerated movement o f a l l the u aselea o f th e body accompanied by p e rs p ira tio n and th e p a tie n t f in a lly be comes v io le n tly m aniacal, shouting lo u d ly , le a p in g out o f bed, attem pting to anadh. fu rn itu re o r windows and behaving lik e a , v io len t aaee e f delirium tremens* Morphine only accentuates the ayaptoas* m e victim may f in a lly d ie in exhaustion* One man anashod a window and out h is hand badly* He had delusions of v isio n , seeing imaginary groups o f persona, and soeusing the Doctor o f try in g to out him up* Another man eg* the w all paper consorted in to swarm# o f moving f l i e s and thought p lo tu ro s o f h is family on the w alls were a liv e and moving about Of the two f h ta l eases the body tem perature i n one p a tie n t rose to 110 degrees Ju s t before death* both these men hod been a t work only fiv e weeks* She e ld e r , 3 years o f age, was not very vigorous, o rig in a lly having a ohronie fib ro id con d itio n of th e lungs* She younger man was o f fin e physique* Sir* hoSann, who has had a very ex ten siv e general p ra o tlo e , s ta te d th a t he never in h is l i f e had seen anyone die in such agony as these two men ae he said "they died y ellin g "* One man had to bo atroppod in bed by an expert accustomed to r e s tr a in in g th e insane* - ' . : : ' V '. ...y.- As in n early a l l poisonings o f in d u s tr ia l o rig in oonside ruble personal idiosyneraey nay e x ist as to bodily resistance Many f th e workmen showing only s l l ^ t t symptom* have continued a t work* In o th e r eases q u its marked, symptoms have developed w ithin from throe to alx hours, In one oaa# th e blood pressure dropped in only three and a h a lf hours a f t e r beginning work - from 199 to 111 - a f a l l eomueasurate w ith th a t which occur* l a am- , aeasivw haaorrhags* - Convalesoettoe from the severe syiqptceHi i s qu it# p retx u eted and may occupy from s ix to ten weeks*** ^ ; , ' A .'U *! ^ > t V1 'y"* . sY- ^V* -1 >,,'; i t \ - ,'* 'Tfp* ^s;' .>%- r 1/ , _ v:.?<X - -' ^- v * ^ * ^ - ^ - ' 7 ^ r-v.-l'?1. . .. k _ *r 2ho follow ing ta b le ^Uioh. was furnished us by th e o h le f 'YY surgeon o f the Pu r a n t Uoi^anyf/r&oord th e symptom* observed l a t&jSv&rSz:-*& $? tw enty-eight ttuoh oases* tf;dVA*tv.i-Jl/hltJ- k/*mn*t.:u".>*k><.i,*mnziP , m .:L u, (Xiio figurea r e f e r to th e m ab er o f eases in which each syaptara was observed) . &\k-i ; - Y3 %jl| IflS U X iT T iiii . . . . . . . . . . . . . . ... . . . . . . . . . . . . . . . . k o m i rt;r v o e f iitin io i. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . ______< - - i e i & $ B Q i m A b d u ra lt * l \ D ^ u A ifs * .* # * -* ..* * * ...* .* * .- tfH a A A n a t.n R il K ttrt ^ f l r i o u i i ^ r : *I 'f i # # U n i i U u e r o r , ~ r \ a n . . . . . . . . ___________ __________. . . . . . . . . . . . ____________________________ . 1 : * i n \ / i a a I t l f i O f w o i i i 'i t . . . . . . . . . . . . . . . . . . . . { ik in fjtv ll tr l i l m f 1 f i h a d b l o o d r /x v ? A tn jr a * * * * * * * * . >1 a w 4 n r o f V t t l l XA p - . l t f i .................................................................................... T ' h r t t n i l i n i i l f t ......................................................................................... ........................................................................... t ' t x 1 1 1 / t . n f l t a I n til* f f l i m t h . . . . . . . . . . . . . . . t./u iil 1 i m a n fc to rt 'l i m a ......................................................................... i.V '*. '. :.! -- i r i h n n p i a . l t r e> * \* * i t u p . . . . . . . . . . . . . . . . . . . . . tiW A f W n n 4 /iU v D f t h f l v iiM n ..4 . ^1 f t 4 n t h r t t i T* 1 k a . . . . . . . . . . . a . . * . . . . . . . .^ A a tn n a i n t h a tiF in f l . . . <. . k. . . * . . 4 4 . 4 . -g e o to -^ n t n a n u ii k 'id la n tm ln i' P a a /iH iw ............................. .............. ' M 1 a t n d v t- tr v v l 1 f t ................................................................................................... 1 + . j* V t tt ii T i f t h f t a / I n ......................................... . . . . . . a * * . . * . tin v lfA il i l r n o A t m c i t i n t h r t d & v t l a n . . . . . . . . . . i t e o d a o h e ............................................... . . . . V ertig o ........................ ..... .. * ....................... I r r i t a t i o n o f kuoous Esoitbranee o f the nose and t h r o a t . . . i^ 10 1 - 4- Xigtgafg '' mi fh physician* ployed by th ese eoagmaies were o f the opinion th a t the t o x ic i ty o f le a d t e t r a e th y l was caused p a r tl y by * ' 1V-V.I.''iTr' >. ' V >*** the sosfcouadas a hole and could not be ascribed e n tirely to lead poisoning. e ^ e o i c ily In view o f such symptoms a s Insomnia and m ental eonitemsnt* Bat In e le v o f the foot th a t l i t t l e haa been known ' h ereto fo re oonaeraing acute le a d poisoning, and sin ce a l l the symptoaa described have been previously described as occurring in ease a o f shm *te load poisoning, ve a re in c lin e d to th e opinion th a t th e .* to x ic e ffe o ta of le a d t e t r a e th y l are elu p ly a m an ifestatio n o f <f aouto lead poisoning. Thus O iler, #(P rinciples and rootloo o f Uedloine, fiin th E d itio n . pass 3*4} says, . Vfls?oiB--acoT5 Wo do not r e f e r here to the acc id e n ta l o r su ic id a l oaees, which presen t vom iting, p ain in the abdomen, and c o lla p se symptoms. In workers in le a d there a re several m an ifestia * ^ tio n e which follow a abort time a f t e r exposure and se t in a c u te ly . >W There may be, in the f i r s t p la c e , a rap id ly developing anaemia. cute n e u ritis has been described, and convulsions, epilepsy, end a d elirium , whieh nay be not u n lik e th a t produced by alcohol* Shore a re eases in which the s c a tr o - in te s tin a l ey&$toos a re intense and rap id ly prove f a t a l . Sheas acute forms occur more frequently in persons re c en tly exposed, and more o fte n In w in ter than in summer. Pa Costa reported the onset of hemiplegia a f te r three days' exposure 1,1"i'.V -r ^ 1 to lead" ' :;:vi ' :: , <r'-. "C ertain o f the cases w ith e o llb may p resen t tho fea tu res o f an , acute intra-abdom lnol lnflss&ratory oondition* A case may be adm itted to the surgical wards with a dia^ytosia of appendicitis, or simulate in te s tin a l o b stru ctio n . hoeulised p ain , slig n t fever, and moderate leuooeytosla may bo present* The h is to r y , the presence o f a blue lin e on the gums, end the blood changes ora o f importance in d if f e r - / e n tia l dio0 no8is* M.n ^;;::;;^\i:-';;:v'\ , . . "The c ereb ra l symptoms ore numerous* aeven o f our cases showed marked c ereb ra l Involvement* Ono had delusions arid maniacal e x c ite - sient and had to be removed to an aeylwa* In o th e r cases th ere occurred tr a n s ie n t d elirium , a tta c k s of unconsciousness, and in one ease oonvul- aio n s. Optic n e u r itis o r n e u r o - r e tin itis may occur* H ystorioal symp toms occasionally occur in g i r l s . Convulsions a re not uncomMon, and in an adult the p o s s ib ility o f load-poisoning should always be consider e d . True ep ilep sy osy follow the convulsions* a b aouto d eliriu m may ;i occur w ith h allu cin atio n s* The p a tie n ts may have tra n c e -lik e a tta c k s ,i whieh follow o r a it e r r a to w ith convulsions* a fow oases o f lead " encephalopathy f in a lly d r i f t in to lu n a tic asylums* Tremor i s one o f th e oaa&oaost m anifestations o f lead-poisoning*" j; m & rn *? t v i& z v :." - i 8 f!lli; *' f iy . x&}xudm*Li Kk" - ,. V " - - . .- V v f f ^ *55"i* v 'c ^ : l'ixe sufi^lo of lea d t e t r a thyl, ,rb (OgHg)^ used w&a furnished by the 2u i ont Company# H o * tra n s p a re n t^ p a le amber co lo red , v o la tile liq u id , p u rity ^5. p e r cent. The ixa- p u r itie s ere o le fin e s . I t deootqposes a t 12Q0. and i s soluble in alochol, e th e r, e th y l bromide and g a so lin e . i t i s s ta b le toward w ater but decos^oses in d ire c t su n lig h t, and was stored in a dark b o ttle in a closet. ^ a . kethuds amiJtasultai \ LOCLL ai-PllCASloa.--Quinea ? ig . Chis te a t whereby a d e fin ite amount of the compound i s applied d iro o tly to t i e eicin o f the anim al, depends upya absorption by the s&in to r i t s toxie e f f e c ts . Che guinea p ig s cheat and abdomen wero shaved and cleansed 24 hours before applying tho co% ouna. Cho p ig was strapped to an operating board and the compound was gradually applied to the Skin from a p ip e tte . Che an1;.til was allowed to remain on the board u n til a l l truco o f tho compound wee abaorbod* Che t i T required fo r absorption was 20 m inutes. She animal wue then removed and placed in th o 'h o sp ita l where symptoms were noted. Che r e s u lts follow 1 00 1 cc 1 00 0.76 co 0 .6 oo 0 .6 oo 0.3 CO 0.3 cc 0 .3 oo 0 .8 oo 0 .2 oo 676 grama Died 12 hours 600 * . - 62 *' 626 H 26 M 666 60 * 620 M Lived 460 Lied 36 hours 602 *It " 60 * 400 ' . * 24 420 600 .H :n '' *18 .'Lived;' ; " / 406 . * . H ; , "' , '>; ;L/\;.:;A . . ' : -VLi;i,.--.:*1.;.* h; Tho average weight o f three p ig s receiv in g 0.3 c c . was 440 Grams. Che le th a l p o in t by lo c a l a p p lic a tio n for guinea p ig s is therefore plaood at 0.6 cc. per k ilo . V s- *V* ', ? . : : y -6 - . .. ' fftimlrffiffl fhe f ir s t few hoax a fte r the ap p lication w t Ma'^-i^' the pig* appeared normal- With the auperlethol a p p lica tio n (1 two hours a fte r exposure, mariced depression i e i noted* - Sh is wee quickly followed by body tremors In feu rh our* tin e the aalaml was h e lp less, the body end ex trem ities trem bling v io le n tly . Death followed in s ix hours At the le th a l point (05 so ) the syxptoma vers the sene as described except the (meet o f the syaptons and death: ere delayed a l i t t l e longer These guinea p ig s exhibited signs o f# ? p a in and tenderness on pressu re ever th e abdomen A fte r death area of application appeared normal. Share ere no signs of ~ eltesm nt noted . - v- - y T y^-> v'\; , . DOCa L A^ ^ hlCASloir.--Dogs - Lo ca l a p p lica t io n # wer e made upon s ix dogs, th e lea d t e t r a eth yl b ein g a p p lied t o th e p r eviou sly shaved thorax and abdomen She r e s u l ts foilow j H. Amt applied ItairiU , 0 .6 00 O.ft so 03 os 0.3 os 0.20 es 0 .2 GO Died 2d hours * 30 * 73 " 180 9 aeoovered M > <1^ 5 i i f- fTJ yv *<r ,,v She le t h a l p o in t by lo c a l a p p lica t io n fo r d ogs was p la ced a t 0.3 c c . p e r k i l o body wel& t . Symptomsi She symptoms follow ing sh in a p p lic a tio n to dogs ware \ sim ila r to those described fo r guinea p ig s . When th e ani."*l received ; a le th a l dose, i t req u ired about h a lf an hour fo r oosiplets a b so rp tio n , -t. She dog was then released from the board and placed in a la rg e cage - ' where he could be observed. She dogs gave prompt evidonoe o f d is tr e s s and. abdominal p a in , o ir a lin g about the oagsv s i t t i n g down and a t onoe ; v g e ttin g up a s though i t was impossible to reach a oom fortable p o s itio n . ) , ' In several in stan ces th is period o f uneasiness was followed by a pro fuse bowel discharge, the faeces being followed by watery f l u id . . A fte r t h i s the dog appeared e a s ie r and would l i e down, h a te r the a n i - ' ale were depressed and comatose, but the b e lly was hard and rig id and - v - p re ssu re Censed in ten se pain Cm th e second day the c o n d itio n wee r much the same, except th a t th e n n im l could only get on i t s le g s with~ri'> ^I f g e i l i j i sl l H.sal|r*.ia! l|,liijZ! t| s,5jii ! lM5 ?l li .m m 5s : sr 3| s3i*iS*psg ,- s !s8 s im a  '* ' ^' - . , , , ......... . appreciably. A fter th e tw e lfth a p p lia a tio n the dog bee&a to depression occasionally *ooe wrTW K ww A fter the e ig a teenth ap p licatio n the dog as aark aily depressed also very unsteady p o n ^ I t s fe e t and the trem bling o f the body shw ed aarfeod Ine rea. , Shin trem bling grcutoally increased patii th tw e n tjr f ir o t a p p lie a tid n had. teen saute, th e dog dying fo rty a la n te a f t e r . So i ta a a n t was: ~ noted. -x* v:; jC3Cir?Ahi(JD3 liJio S lo a.-^ ln e a.l:lfi# r< -.-- 5?wo-test nor v&i by subcutaneous in je c tio n . T hepureooapound w a s d ra w a in to a darai syringe suits fllot and injoo ted under the akin -, .V.-. ~ <;. /'> of tho an-ri m is"Sv*s"k#'. T,-.hye ' '* >`u Amount In je c te d ittrtriltA S ftflfcSftL * '& V 0.25 OC 0 .1 00 CIO granb tQ 0 " > . >v - V --, ' Died 164 hours 96 : 'v-Vri?- M tim x fh syagptons were sim ila r to those noted under Xoo&I> a p p lic a tio n . The a re a o f in je c tio n a f t e r death uppsared nom ai ...... M iiUhCUTii&iQCS lltf^TIO H .--Cumulative E ffects.- -Guinea r ig a i ' 0.01 e c . in pure olive o il in jected evory twenty-four hours. Three guinea p ig s were selected fo r t h i s t e s t . Care was used to s e le c t pigs o f tho same w eight. The re o u lte follow . ^ fw n t laJfigj&ft. . : 0 1 01 .01 .0 1 .01 01 .01 .0 * <aaiX3Lj?AjJi$ M g 640 grama . -- 640 rt i: i 640 M 640 M \ 640 " . 640 , ,, >-<C 640 640 " l" " o/s o/a o/ s 0/3 1/3 . */3 2/ 3 3/3 . X.'-i---: ; i-v> . , , &< .`*7 sb a r * ; O.vsfcTtomsi The f i r s t th ree in je c tio n s did not appreciably a ff e c t the anim us a f t e r t h e fvmrth in jo c tio n ono p ig showed narked body tretaora, while the oth er 0 pigs wore t^ rk ed ly depressed.'" One p ig died Sixteen hours a f t e r th e fourth in je c tio n . i* hours a f t e r the f i f t h in je c tio n the second jpig was seised w ith body troooro' '' and diod a f te r twonty hour. one p ig survived for tho eighth in je c- " tio n dying twenty-two hours a f t e r . ; There was no narked e w ite a e n t .noted. :X.vjV-.',. ^ . - .. ,.-.-... .* - rv-.-.; " ::6.: " ~7 , rJJ- . 4 .' - 1- M;.r ^ v j '* ' ' Vv*'>^*;*; , k`~w ' l^ r ! j `- ' r'i\,-* ' j >' 4_ , -'"WVIfSe'*r;*r , * .* -.-'iX": ' "& >:. .r( "' 4 ' ' j V ti , ' - ' . -' * ' rr ' | i V ,, - ' -, ?>. - S *; ' . 'A 3 C. v . * 4" " * - *-T V :*' v v - ?***&*&$ i-.{ ;v*'-' ; ','" 'Y . >*-- . y HffMYoo3 iw azrioH .--Dogs* C '- M rs dogs sns used in th is t* st* - fur o liv e e i l v m used u d ilu en t for the compound* Che u n i t i jteU w i j<V* 'Sir*t? *>* 5 * *r ^ V ^ Amount Injected raig KUq s^ tote, n tfih l h w 4-i 4( J ltl V K : ^ r * , ^ * v * ! ? 15 * 0*078 Died 14 hours . T 0*038 -/$ 0.011 0*0088 <^P *V-'w"*"4A,,.l. * ftr-y'v r 0*0086So I r ^ ` Tv >*v,, < ,, *-. * 14 - * y -m ' 8 * w (\ t> ^ 884 (delayed) h ived , <, v ,* r - ^ <,, t p * * . / - She lettasi point fo r intravenous In jectio n for dogs i s placed s t *011 so* p e r k ilo "body weight* ,; - ' -y\ Smatassi Doe injected intravenously showed almost l amed sad asuked q. ra..ptC N. .ft.on the c'ompound* " gite minato* after b' eing i`a-I-4t, Jested f the there were nuked twitching o eyes end aeee9 sad tepid brea f th the ing , face sad eyas, followed by rlxaechd ryens as tiitoen- ?m* m a t la s tin g f o r one hoar to two hours* During the f i r s t hour after..:, the injection a n issle/ran lted blood stained m soos and diarrhoea J ^. a ls o proteoed* - Vhe e je o tio a from the bowels howeter did not ^ p o o r lip l blood stslnod* The sa slte a ttt may h ste boon caused p e rtly by o o l i o * ^ ^ She sta g s o f e s o lte s m t wee followed by e o lisp e e , th e dog becoming h e lp le ss w ith seueksd trem bling o f the body end e x tre m itie s u n t il death* *c"*ti<< 7^f vSrfS . < XHBAhm on *~ -itlee* A namber o f t e s ta were ron on mise by th oontim ou* Aow msthod t e d e te m in e th to x lo ity o f th cocqxmnd by inhalatitm * Sen adante erj^osures to a gs'slr. mixtnro of th etnpound were mode f is e idee being used fa r esoh conoe n tr a ti on* : - , i h e ^ | versge tig h t o f th e le e mas twenty grame* She o o n stru o tian o f th ; mouse chamber w ill be fbund in r e p e rt .a *^*1UD* #U * Che ro s u ite . : ,;r fouevt ,, .-. ' , X :l*\ - -r 1** ; ' w ' ' \ v-^ 1 ' jVrj * y > ' ' ,*- ii'-. -r\fw ?<i-'iz'.f- > ;t 1 "5/ \`i^ t S ysyJ'-v r' * kf% * * .j S , * f +-. :vrH>r.i' pigd&t. . v ,i . ** -1 0 - i* .'t "*> tl n-v,/- t f 0 0 1 16 ,v.'`p ' ia <- ? ;' 4 - CoBBantration g a te foat e Tt},fTi^ ffrffith 6.698 6 .U 4.968 4.1M 5.679 3.617 3.426 2.612 1.615 0.71 /fi 0/ 6 5/fi 0/5 0/5 0/5 0/* 0/5 0/ 6 0/5 0/ 6 0/ 6 0/fi 0/5 0/5 0/5 0/ 6 0/ 6 2/5 -- litlli The le th a l oozantr a t ion fo r mice by in h a la tio n 1 placed at 6.11 milligrams per l i t e r . aymptoset She mine tiiosed a c t iv i t y while being exposed to tfe* gas a i r mixture o f the compound. Upon removal from th e gas the a le e wore markedly e x c ite d . In the case of le th a l dose the ea eiteo e n t gavo wy to arfcea depression follow er by ool lap se, trembll and death. ' ' - - ' , '~itL XhHAhASlCHf. Cumulative a f f e c t s .- - h i e s . trice MIOUBJol&tive e ffe a ts o f the eompoand. i'un aio ware subjected to m :oonBQ&txotie&s of 0 .5 m illigram s p er l i t e r fo r ten minutes ease very tw enty-four hours, the fcoaple being oheungad f o r aaoh ru n . va * i ' ? : , A fter tho fourteenth ru n th e re was one d eath re s u ltin g from th e c o o -; pound. The fif te e n th ran produoed two d e a th s,th e n ineteen th run ` one d eath and th e tw e n tie th run one d e a th . She t o ta l nucfcer o f \ ' th irty -tw o , r e s u ltin g in fiv e deaths from ta n doe used. She r e s u l ts follow V' t'-'-x;-," .... " ., . - .V - \+ ; 4r;.t 'V .v - '~7;'ZMri \:^y * ;-*^r :-- ; r . '' >i^V 0m m m - '... y ' F - t K -v ' -Cr.yi; . :-v; /;,*. .** . .- ..J-*'v tA* JF -^ -fe. *' . JT ' - 001771. aaaaaaaaaaaaa' f */ / , ,\ t , * y ' ' y**.' ' - \-, * ta il |i I0 ., il O il "4\ : wa II11 i . i l i sf f :' .vV; . *. k}:0:S. V- Ifeta b o llsa I f wo aaauaju, aa 3 liKliautod by th syKittom, th t tho to x ic ity of le a d t e t r a ettari io due to th e lo u d uto&t ra th e r tiiaai th o n tiro tuolo cu lo , tudy o f t h o iaetfcboliaaifi o f ottj.ecitd. . in te r e s t &s ohowing a new fo ra o f acuto leoci poisoning. For wo iure d o tale ti w ith a h itlily lip o id aolublo lee d ods^ound which le eupable o f a2in penatrutiun end whioh, fortherar, i ooop&nativoly atab i e . Xt la prob&Ll; th o only oocpounci hero acute lw4 poisoning followo absorption th ro u ji th skla. ,,, ` ;>& ;, In cUrohio le a d polaoning th alcoleton o f tho body hoc West shown to bo tho atorehouse for tue ctj*ratl're ly la rg o aaovuit o f 1 oeowoulatod. la acato leud poiaonin<; d ia trlb u tio n le tlmrogbout body w ith th u rino and facce a* th Bouree of e lio in a tlo n * 31 n atio threrush th ffeooos t&ces placa ovest wfacn obso letio n la tkrough thu r e s p ir a to r i t r u c t , probttbly by e x o re tic ji ir th liv o r olona wi th b ile . . A nu/aber of anttlyeos wei*e cade on organa fruir, both doga . gu.lna& p l t>a of wuich th bc>t oxai^lo i s th sy atea*t i c atuuy o f dog -*% 1662 as givo belo 1211 Weigit 17.7 tgs. (J1voti a sin u n l i c a t i o n o f 0.26 o c, 1ead t e t r a othyl per itilo body w o ijit, equivalenti to 4.4; oc* or f> Daya a f t e r Urina Voluta 6oad Oontout jfccOes V.t , head cohfcent application oc k v is. grafia niga. ' . '.- 1 z 3 . .. 4 ' ' 5. 6 .: . . . 7 .: . , - /;'yv - 8' V/ . 600 . 330 ' . 340 160 . - ' 133 - , . ' 166 nono V 260 ' : . . 2,04 1.32 1.03 o.a . 0.6, 0.6 0,6. .. 36 6 ..' ; . ` , ,'' - 10.6 n3.0 ; f l i The dog vaia k ilio d and aatopslod on th o itfitk day. - >* - ' 13- mm '1 llf -w HE ooi77.ni  7'-- js c brain .' fiant " ' Intestines, asoli Intestinoci, lore Eidney c' liv er { lUBg > Skin, avo o f ap plication ( Spiata ' - *, t is 7 v'"A`'s M 11 ' ' ' * *** l i I t la soon th at approximately on* f i f t h o f o i l th a load appli tras found i n organs and tis s u e re p re se n tin g on* q u a rte r th e t o t a l w e ig h t o f th e dog fh a amount exoreted a s vary s n a il, amounting to only on* p e r cen t o f th e t o t a l applied* In a nas&er o f o th er anim als th a t hod resolved assail doses tita he fora being k ille d , in the a n a ly sis o f th e ir organa no tra c e o il lead w&o found* T his would in d ia a te th a t th e load was referred fro ttj body tissu e * and deposited, probably in th e sk e le to n , - 1`i"' Since the amount o f lead easero t od in the faeces and u rix i a | ^ ^ voty sm all, i t is easy to undorotund how secoli amount* o f le a d t e t r a e th y l| aay have a otunulative ra tio n Sho d ifferen c e s in in d iv id u al raso apt i - ^ b i l i t y to t h is cutanlative ra tio n a re probably to be expiainod a t le a s t p a r t i a l l y by the d if f e r e n t r a te s o f e x c re tio n of le a d b y d iffe re n t in d iv i4 - |i uala I t la evident from the very su o li le th a l dose by intravenous in jo o tio n (0*011 co*Jt th a t very aemll amounts o f le a d i n the e ia c u la tin e fcio o d ||| a re productive o f serious dis tu rrara* of the raramra system, and also Itsvs ^ a d iro o t e ffe c t upon the in te s tin e s producing lead r a lle or even ulceration! Shoe* r e s u lts o f the m u te ra tio n o f lead a re p rec ise ly s im ila r to th e *3*itoa* o f chroalo intoxio& Uon, * n * p t th a t they o n maeh or* T lolsnt ' . >s**- ' / f ivb1*. & *> *-*7- ** s 2^ +*>*1 r- - "> VF7P- -sr*-'****-?t,+ $J^O,3 ^ fV Lf-J ? 1 **? *$ y` *$5 A ^ V H- * & , V iti,r.i<<'*nv .?** ? -14- 7i s >* KE 0017 "Vv` '** >**' 7^ :,;<^r^&ciS? 1v ' vJ i4 iW',,r-vv--' -. ,- - V - % pmr'KtLAXlSi '> ' i y ~ . % , ; - r s? * -1 is Counteracting the e fto o ts produed by kin application* ChpMleftl agents wore used to eounternot th e e f f e c t s ' produced by applying load t e t r a e th y l to the sk in, ; l a these te s te a le th a l dose was applied end the obeoioal .gout applied iaoedlat afterward* Hydroohlarlo s o ld l a stre n g th s o f l O ^ S f i ^ h O ^ a n d Q*rfj w on used and found to t o v alu eless* G alelnn H ypochlorite a wood; both In tin fe m o f a dry poodor and paoto aad was found to have no value* fh o Vain o o f So lve n t * l a a a et o vln *.Lana T e t r a fi t t o li a n u ab er o f s o lve n t s were u sed t o r eoove th e lo a d t e t r a e t h y l b e fo r e a s n fiie ie n fl q u an tity to prodnse death was absorbed by th e akin * l a tho fo il* e xp o r ia s n t s t h e an ima l e u sed w ere (soiree p igs * T h e w w u n t o f l e a d l t e t r a o t h yl a p p lied was a s a p e r le t h a l d o ( l oe*)* The r e s u lt *; " follow* . -- : 1 ` .' - :/ HxperiBant #1 - OllTO Oil V. : ,, Two p ig s wore cleansed w ith o liv e o i l one sdnute a f t e r ap p licatio n ^ o f lead to tra ethyl* Both p ig s died* . ; .; \ \ r - ~ 7 '&$8X : ' ' " ihq>erlaent #2 - Ordinary Soap end ^ a te r : - . ' 2 m pige were cleansed w ith ordinary soap and w ater one m inute; a f t e r th e a p p lic a tio n o f lea d t e t r a ethyl* b oth p ig s died* -> ^ Ssperimonfc #3 - fin e tare Qreen Soap ' ' ^'AM, Two pige were oleanaod w ith tine tu re green soap and w ater o n e \/| |p || minuto a f te r ap p licatio n of load te tr a ethyl* both p ig s lived* \ Sxperlswnt #4 - T incture Green Soap Two p ig s wore cleansed w ith tin c tu re green soap ami w ater two a la u te s a f t e r a jv lio a tio n o f load t o tr a eth y l* doth p ig s lived* ,, . s? M-WM Experiment #6 - T incture Green Soap ,? 'SB Two p ig s were cle a n s e d w it h t in o t u r e gr e e a soap and w a t e r f i v e Bin a t e* a ft e r a p p lic a t io n o f le a d t e t r a e t h yl* Sot h p ig s d ied * .'H i' Sxperlswnt #6 Eero sons -' 'k f i - i ^ Two p ig s were cleansed w ith kerosene one minute a f t e r a p p lic a tio n s ^ o f lead t e t r a ethyl* Both p ig s lived* vv. ^ . -W Sjqx&riasnt #T * K erosene.........~ . - - *.4**^ .* ' Two p ig s were oleaased w ith kerosene fiv e minutes a f u r a p il i c a - ." tio n o f lead to tm ethyl* Soth pigs lived* . .^ < v - 'ttsn:feCtf*- .` .i.-.V. : 1 IS --. Vi - <4w r-f- m ,r * r ' - V- \ <- f r ' . -v- i'TT-.-r.''V&ri }siff i7Xii? ' ,.,X*p. *'0^ --^Sir'" ' -'-i' \ u ^ *" >v* \ >-Hj <"-vsV, '.'Si' ' Experiment $Q - Keros followed fay T incture Green Soap end V oter / Two pigs were cleansed w ith Herosene w hiohw asfollow ed, tgr . tin c tu re green soap end w ater ten minute a f te r ap p licatio n o f le a d 7 te t r a e t h y l. Both pigs liv e d . * n '/ ^ ^ ' : - * V- - U ** r.v`-i - - - - \ Bsperiment #9 - Kerosene followed fay tin c tu re Green Soap end Water Two pig a were cleansed w ith kerosenefollow ed fay tin c tu r e -'greeaj soap and w ater fifte e n adnata a f te r load t e t r a eth y l a p p iio atlo n . Both pigs liv e d . -. .. - -. Experiment #10 - Kerosene follow ed fay T incture '.Green -Soap and V a t o r ^ Two p ig s were cleansed w ith kerosene followed By tin c tu re green"; soap and w ater twenty minutes a f t o r s p j i lout io n o f lea d t e t r a e th y l.? Both pigs lived JKi ss Sffi Experiment #11 - Korosoae followed fay T inoture Oroen Soap and V ater Two p ig s wore cleansed w ith kerosene followed fay tin c tu re green W t soap and w ater tw enty-five minuteo a f t e r a p p lic a tio n o f le a d to tr a . m wM e th y l. Both p ig s liv ed . Experiment #12 - Kerosene followed by T incture Green Bo&p and factor Two p ig s wero cleansed w ith kerosene followed fay tin c tu re g r o n * ||i^ soap and wator th ir ty minutes a f te r ap p licatio n o f lead te t r a e t h y l ^ ^ One p ig liv e d . One p ig d ie d . -. ' ^ ^ . " Experiment 13 - Kerosene followed by T inoture Uroon Soap and f i t t e r <$ %'%'y ^ four p ig s were cleansed w ith kerosene followed fay tin o tu re g ree n -^ .^ 6 ; soap and w a ter. Two pigs were cleansed th ir ty - f iv e minutes after exposure. Two pigs were oleanaed fo rty minutes a f t e r exposure. four pigs died. AlllC $v Iw Oonelusiom Both o liv e o i l ia oocnson soap and w ater proved v a lu e le ss as agents to remove the T inoture green soap was o ffse tiv o lead te tr a eth y l from the okin. i f used w ith in two minutes a f t e r tho <^' r%\i a p p lic a tio n o f the load compound# Kerosene proved to ho the bout agent t r ie d , a l l pigs liv e d tfabt wore kerosene tr e a te d up to th ir ty minutes* I t was observed th at the skin of the pigs te a t were tre a te d w ith korosons alone become te n se , in te r f e r in g w ith th e movements o f 4 th e eaiJm ls. Tho skin would a ls o oraok and to a r causing g re a t discern* f o r t . ' I t was fotmd th at follow ing tho a p p lic a tio n of the kora sene ; fay tin c tu re green soap anti w ater removed the korosose lea v in g ths skin s o ft and p lia b le . ~ r. - / - h e DO 17*7-'2 -16- *^rV ? vs 'i-A t > W , >**V a#** -vsi --S4*1 t4 'S /:v /,* v * f-} V- >{* V* , -, ** : '- \V.5 .>/ >m r-', . 'v ;> W # r A 'iS**K*$*v **"* ." ' *. ' vt , ,,.'* i #<t.':->vr.'' *' > * -<. ,-> 4 frv^ ' 'isf ;% *v i f' I 1 quita rldont fro* thaaa ofeaerratioaa tfeat tb aanu&otora, bauHing and d lstx ib a tio n o f load t a t athyl ta ro ln * ctmaidarable daa&r to operative e t Mut laad poiaoala la thoao lnatsnoaa har considerabla waterU l ia aplaahod pon ft alela, <# ? * and of hroaio laad poiaonine trm Iba a&sorption af M ail aaounti 3 : hy Inhalation, by tho skia or by ooutlu fasta by tha Buraca o f __ = lO&ss appacr to abo* tfcat load tetra othyl la aadwost gasas o f . uM aalonobllos la not toxio to aal&ala fcavi&g baos.ebo&ged to Inoo!*'^ ttt foros o f load 1 ^H.H ~ Zt l a aot b o lla ra* th o t t h is ooqpcm&d l a o f eny^graat^ alna a s a a rfa rs agsnt beoausa o f I ta low to x lo ity aa a Vapor, and th a i* ct th a t 1t doaaqpoaas a t 1S0C* ltfcoogh opinabas o f ~- th ia ll^ a id o& tha akln w ill prooaos aath , I f te x lo lty f o r sa n io a la i l a r to t a x l a i t y fo r doga l t woold raq u lro 21 oo# to oaaao tbo doeth o f a an* Shas l t oould harly ba usad aa a pruy f o r . j leth& l affoot althoufih posslbly a a o rta la noaber o f sa a u a ltie s tfVK eould be ao produead - J J: to* tg s / 'f e byj fr y /t/ q j,. Wf* TA>". ld r id es* / ;:. Jttittte. ai. SfflrfglU i ....ffSitfk_________________ <*&>.**.* 3nporvIa*d Dyj D. G. a n iton , Lt* GoaacLr., li*C*t U.a .J U , Chief, Bop* t* of cadoology. Approved fcyi r, nk^i/6- t^ c li . " idtwnrd , V'o d -e r , , It* CO*, &*C*, Chief LedIoni Haofcrch Division* \::^4 W *> Wo lugani ' -' Ify 7,1924* Wo eoaletodt ; Oetofcer 6, 1924* -t > J T F*r.y ^ *t* * * w ** /*** ** >f *SW4;V- *'*V'* V** ****? * -iP- s.->V- -, ce o o p isi ' *>.> ->** ' ' (oofiodt d f) :,z:0'v: /^r// k s* ` I 1<V>\V^l .rS^-.-rl V^j?..Sv .s f- t ft-t * i - - Hr*' * " " -V