Document qov41Oj48JKeDMXkkZMnnL0M

T < ''I \x :y'-l"*? . -i * A. iildjiutsa -mm :^V v . * -r';V.'1 - a ^Sr < * A tfgpat 09 TH3 TOXICITY ft? LifliP Tjffl3A ESttL*- \ *jr I?* A* hldridge fC la, .... I?f^'UtJCTlQtfi . vy. ...........................- ^ v . . *1 IS .= 1 '. She object of the following tests was to detenslne th -* toxioity of Lead Totra Ethyl upon tmixaalg and to study the ayaptoas produced toy this oaepouad* your different mthod* ware used to .-,}. adsiinister the compound and lethal point a were established by eaoh aethod* The aethode employed were as follower Local application* h subcutaneous injection* Intravenous injection*, and inhalation* ll.. amUdittt. 1* The lethal point by ascia application wua pieced at 0*6 co. or 0.996 gtm per kilo for aiuoa pigs and at 0*3 ee* or 3*498 grwa per idle for dogs* 1 co. of pure Lead Tetra Ethyl weighs 1*889 grans* 2* The lothal point for guinea pigs by subcutaneous in ject ion ie appraximtoly 0.06 ac* or O.lSii gnus per icilo. 3* Tlte lethal point for dogs by intravenous injeotion is placed at 0*011 oo* or 0*018 grow per icilo* 4* The lethal concentration for doe by inhalation is placed at 5*11 otiUigruHs per liter* 6* The evidence indieatos that s&ulier doses are cumu lative in action by whatovor route ocuainietered* > 6* b hen an auinc.1 .receives a lethal dose by shin appli cation* Its life nay be saved by washing with heroeene followed by tincture green soap aM wutexv provided this treataent la curried out within thirty minutes after epplioation. .. V.fsi;.;;V- ' . a f A -i- ,j i S. wi ~ K Aw **; uh uimuttki. > ~ Althtwgh ehronle lead poisoning is the canonest of oil fbrns of Metallic poisoning, true acute load poisoning, that la the offset of sudden absorption of loud la nea has boon hitherto 1 unknown. Wien a large quantity of sene soluble salt of load la shallowed,it gives rlao to tho ordinary sya^tosts of irritant poisonings nansly, nausea, ratalting, pain la tho abdoaon, vio lent purging, weakness and collapse* vU?' rd " 7*y la enlaols also, it has boon difficult hitherto to pro- doao acute load poisoning because when aoat fsnaa of load are in jected tho proteins of the blood are praolpitated aad death so prodaood ia purely neohanlcal, aad only local syaptoa* verb pro- daoed by adxsinistrut ion by aouth. Eowevar Harnack Injected salts of load triethyl* In the frog this produced general paralysis apparently by tho action of lead on the central nervous aystea* ' 1s0k: ,, TgsSf la the dog tho sjo$taes following intravenous infection wore weakness sad paralysis, violent diarrhoea aad oollo, ohoreu-llfce aoveasata, trustors, sad convulsions* She diarrhoea was found to be dee to violent contractions of the Intestinal walls, which Maintained a degree of contraction even whan no peristaltic wave ' %p ;~ J*4,*-th*fV-.r` -V> '?5*' | passing, (Cushay - fhomteology and Therapeutics, pegs t&3. j ` E 1 V-t * 4* Lead tetra ethyl was developed by the General fcotors and Pu font eorperations as an addition to actor fuels. hut soon after large scale production was conxaenoed, a number of toon handling this product booamp ill aad several of then died. The following dascription of the syatitoo* was included in a report to the standard Oil Gocgtuny by Brs* Thomson and sohoonleber, rendered hay 10, 1934. "The first oyaptons observed are a storked full in blood pres sure soaetineo as low as sixty points below nona&l. Thsre is an aeoos|)snyittg fall ia body temperature which has been recorded as low as 94.6 degrees fehremheit or four degrees below nonaal. The heart action is slowed, the pulse having dropped In one case as low as 46, that is, twelve or store ocunte below nonaal. There is at first sons digestive disturbance, such as loss of appetite, vomiting and a tendency to looseness of the bowels. Vertigo asy be present. The red blood corpuscles show narked changes in size and siugo. The blood in one of the fUtal oases fUilea entirely to 'fc&.Vfi, coagulate and at autopsy showed an unusual color euoh as is ob served in carbon monoxide poisoning* There is no cyanosis and no shortness of breath* nor ia headache or other pain eoqplalned of. She urine rename nortsol usually bat in one ease reported . treated by Dr. Akt of Harvard lead was present In It* following these syG^toos in severe oases other phenomena appear indicative of profound cerebral disturbance* The vietin suffers fro* per sistent Insomnia and becomes delusional, extraordinarily rest less and talkative* 81a gait is staggering like that of a drunken nan* but there ia ne paralysis and convulsions do not appear* Share la txsg&erated movement of all the uaselea of the body aocoqpanlod by perspiration and the patient finally beecates violently maniacal* Shouting loudly* leaping out of bed* attempting to anaSh furniture or windows and behaving like a violent oaee of delirium treruns, Morphine only aooentuatea the syqptans. She vie tin nay finally die in exhaustion* One sun smashed a window and out his hand taidly* He had delusions of vision* seeing imaginary groups of persona, and accusing the Doctor of trying to out him up* Another nan saw the wall paper consorted into asanas of moving flies and thought pictures of his family on the walls were alive and moving about* Of the two fhtul oases the body temperature in one patient rose to 110 degrees Just before death* both these non had been at work only five weeks* She elder* S3 years of age* was act very vigorous* originally having a chronic fibroid con dition of the lungs* She younger man was of fine physique* Sir* McCann, who has had a very extensive general praotloe* stated that he never in his life had seen anyone die in such agony as these two sum as he said "they died yelling". One man had to bo atroppod in bed by an expert accustomed to restraining the . insane* As in nearly all poisonings of industrial origin con siderable personal idiosyneraey may exist as to bodily resistance* Knay of the workmen showing only elicit symptoms have continued at work* In other oases quits marked symptoms have developed < within from throe to six hours* In one on*e the blood pressure dropped in only three and a half hours after beginning work - from 190 to 11* - a fall oomusasuruts with that which occurs in an- , eeseive hemorrhage*-^ from the severe ronqptons is qoito pro! rueted andmoy occupyfrom six to ten weeks*** ^ Vs*# V %vv=vy', KE* 001770 y *r J~l * j * surgeon 2ha following table nfeioh was of the Pu i ont Uoi%unyf'r coords furnished us the syeptarns by the ohief observed la *?>#*A&- ;<;,& . v71jvs'V.'ij -**:-.*'*'.? M00*twenty-eight suoh oases. ijtQmiiU. ii.iA/rdt .o , III TfeiffX"aA.ill? Sha&i (Xiio figures refer to the maber of cases in which each syaptara was observed) t.-A/s-.v*v*: / S* *'&*&*fw.'*eA&? Insocania #*... j-t anorexia ................................ ............................................. 18^_ hausen ......................................... ......................... .. homing vomiting. ..................... . . .................................... ............ 10 ^ obdar^inul ortuaps ................................................... ............. 12 Uneoouotaraed and annoying dream........................ ll^'T^; Bodily weakness......................... ............................................... .. 16 *;4t J Decided loss of weight ................... ................... 9.*|/~- iiarxodly dimini shod blood pressure 20*`5\;^' glowing of pulse rate ..................................................................... 7 ' & ;hotophobia ............................... ............................ .. ......................... '{5l> Lotallio taste in the month ................................ * 6/^V" Load lino on the guias ............*.................. . 4;V dubnoru&l tfceperuture.............. 19 Hyper-acidity of the urine ...................4....*.... 10 ' ' Albuiain in tno urine ................................... 2, , Acetone in the urine ....................... .................. .. 1 g*ir. teat for load............. ............................... .. 12 ' v Jrerun's ......................... .................................................. .. _ 6Jf " 15coto;au ................. ........................................ ' Increased isuttcular reactions ........................... 7 Diluted pupils .......................... 1 Itching of the shin .................... 4 I&rhed drowsiness la tho duytino .......... . . .. . ..... 1 dlusdsb pupils ............................................. 2 Keud&oho ******....**.** 7 Vertigo ............................... 10 Irritation of kuoous BouJjrunes of the nose and throat*. l 4 ^*&sfVv*J^t-**A***w Ja hcLyfc*. <Tft -4- *'"A*. 3?t , * **N*/ * < fh* physicians employed by those companies wore of the "*,**'j'JMt**4:**>'^*t! opinion that too toxicity of load tetra ethyl was caused partly by 5M--*<i'v-*f\,2,,~A - ths tv^ouai as a whole and oould not ho ascribed entirely to lead ^ki' poisoning, especially in view of each symptom* as Insomnia and JBe&t&l eanltoment* Sat in view of the foot that little lias been known heretofore conaeraing eoute lead poisoning* and sinoo all the symp toms deaoribed have been previously described as occurring in eases of ehranie load poisoning, we are inclined to the opinion that the * toxin offects of lead tetra ethyl are sluply a manifestation of aonte lead poisoning* Shua Osier, (Principles and imotioo of Vedioine, Hlnth Edition, pum 394) says. . *avp ?0V3--j>xxj2a 'ifcsu**--Wo'do hot refer here to the accidental or suicidal oases, which present vomiting, pain in the abdomen, and: collapse symptoms* in workers in lead there are several manifesto?* tions which follow a short time after exposure and set in acutely* V ,, Shore may be, in the first place, a rapidly developing anaaaia* Aeute neuritis has been deaoribed, and convulsions, epilepsy, end a delirium, which may be not unlike that produced by alcohol* Shore are eases in which the gustro-Intestinal sy&$toas are intense and *>%' * -Stf- w/f* rapidly prove fatal* Shese acute forms ooeur more frequently in persons recently exposed, and more often In winter than in ha Costa reported the onset of hemiplegia after three days' steamer* exposure % i.` to lead** "Certain of the cases with eolld may present tho features of an . acute intra-abdominal inflaauratory condition. A case may be admitted to the surgical wards with a dlaiMoais of uppendloitis, or simulate intestinal obstruction* boeulised pain, slight fever, and moderate leuooeytosls may bo present* Xhe history, the presence of a blue line on the gums, end the blood changes ore of importance in differ ential diaGnoBis." O '"She cerebral symptoms ore numerous* deven of our eases showed marked, cerebral Involvement* One had delusions and mnincal exeltement and had to be removed to an asylum* In other oaoes there occurred transient delirium, attacks of unconsciousness, and in one ease convul sions* Optio neuritis or neuro-retinitis may occur* Uyaturioal syraptoas occasionally occur in girls* Convulsions ore not uncassMon, and v in an adult the possibility of load-poisoning should always be consider ed* rue epilepsy y follow tho convulsions* . a b acute delirium smy Odour with ha.lluoinations. Jh patients may have truioo-liica at too its,/ which follow or alternate with convulsions. a few oases of lead encephalopathy finally drift into lunatic asylums* Jreaor is one of the caa&onost manifestations of lo&d-poleoning*" -6- xt oor<T'i 't?** "- 1 / .A - ' - ` S'- fi IY. XXi-it.:iadffl^i , A* ' - . .- - / vff t The sau|jle of lead tetra ethyl, rblCgHg}^, used was furnished by the Du lont Coiqpany. It was * tnoutyarent, pale ember colored, volatile liquid, purity V&. per cent. i'ne im purities were olefines. ,It docoiqpOBes at 1206 and is soluble in alochol, ether, ethyl bromide and gasoline. It is stable toward water but decos^oses in direct sunlight, and was stored in a dark bottle in a closet. S. teetheda and Ifrnmlt si .s.; \ LOC*L aiPLICATlOD.--Guinea Dig. This test hereby a definite amount of the compound is applied dirootly to tho skin of the animal, depends upyn absorption by the s&in for its toxle effects* The guinea pig s cheat and abdomen wero shaved and Cleansed 24 hours before applying tho coB^ound. Tho pig wus strapped to an operating board and the compound was gradually applied to the Skin from a pipette. The onU-al was allowed to remain on the board until all truce of tho compound was abaorbod. The tl ie required for absorption was 20 minutes. She animal wua than removed and placed in the'hospital whoro symptoms were noted. The results follow* &mnt..jauaaUfl.4 ! suits 1 00 1 00 1 00 0.76 CO 0.6 oo 0.6 oo 0.3 CO 0.3 CC 0.3 oo 0.2 oo 0.2 eo 676 GpUttB COO 4 626 n 60b 660 460 602 it 400 rt 420 600 .H :n 40b . : Med 12 hours . - * 62 26 I 60 * fr Lived Died 36 hours " 60 * 24 * 16 H. H It .'Lived." . H ; -ti :Sf'l k "4" y;c- Tho average weight of throe pigs raceivlng 0.3 cc* was 440 grams. The lethal point by local &pplication for guinea pigs is therefore plaood at 0.6 cc. per kilo. ^;r:r'':;'V ;-*? .; -44# -6- K 0017712 44, miSm rtWlrTTnm *hc first few hoar* after the application was the pig# appeared normal# tith the auperlethal application (1 two hours after exposure, narked depression lei noted# Shis wee quickly followed by body tremors# In ftar hours tine the enienl was helpless, the body and extrealties trembling violently. iDeeth followed in six hours# At the lethal point (0*3 so) the symptoms were the sene as deserthod except the onset of the syaptou and death were delayed a little longer# These pilSM pigs exhibited signs of|i|p pain and tenderness on pressure over the abdomen# After death t>-- -- area of application appeared narml. There were no eigne of ex citement noted# LOCAL AViLlCATlou.--Dogs# - Local application# were made upon six dogs, the lead tetra ethyl being applied to the previously shaved thorax and abdoaen# The results foilow* fir Ant# applied ner kilo body wi_, 0.6 00 0#3 oo O.fl os 0#9 os 0.26 oo 02 eo HaialU, Died 2d hours * 30 " 73 " * 180 * Deoovared V '>-.V . *-v ; - r'v' :'-x -?4- >.V . The lethal point by local application for dogs was placed at 0#3 so# per kilo body wsl&it# Syaptome ^ The syoptom# following skin application to dogs were \ similar to those described for guinea pigs# bhen the animal received ;./ a lethal dose, it required about half an hour for complete abeorption# X The dog was then released frost the board and platted in a large cage where he could be observed# The dogs gare prompt evidence of distress and. abdoMinal pain, oiraling about the aage, tilting down and at once ; getting up as though it was impossible to reach a ooafortable position# ) In several instances this period of uneasiness was followed by a pro- fuse bowel discharge, tho faeces being followed by watery fluid# After this the dog appeared easier and would lie does# Later the ani- ' male were depressed and eematose, but the belly was hard and rigid aad^, pressure Caused intense pain# Cm the second day the condition was ~ noah the sane, except that the anlml could only get on ite legs with V*- '  ........... ,,..... * / -ff' \ <iffiat| : < s * ** <-4, 4^-r^ V^>* ** -'' &*'"''' fti miN Mly wU y tsN M rigid and tbi ** Mm w* vexy tenter to pressure* later tiwabliag of th* llaba ^4iWoeMwteWa, Vdt*h^eb#r.h'.e-.jt^etvmaleaiownesre, - eaaolAllla._ipdaldeJo_a_rn-ad__ndd*ega-r-tah*d*-ualllay the aae ef diaaspeared rublethalA ,A m the^S^s* ,,!!...--1., , . V - .-/ . Patholagvt Atttapalaa were perform* mi tear tegs dyingafteryj taking akin apjdteatiene o| led tetre ethyl. v < 4jgiU- She external swpearenee and body oavitiei were normal, eept "` in n ftM Za tela ease necropsy mm porfoamtA immediately after teeth ahUh tecarrte TB hoara after the application* tea eeeeped as aossas tbs abdominalwall was opened, end the scell imd largo iates*, tines wax* acutely Inflamed, probably as the result of perforation ofJ Mf the anasreua ulcers* la all tear asses the heart, lungs, ' apl aadL liver showed no ehanga hat there mm s slid congestion in all ^onss of the hidmy* One ease had a aorsal intestinal txnet. la three eases there were steers throu&out the intestines* these were la the region of Beyers* patches whieh were seellsa sad prominent* the ulcers ware 1 sr 1*5 aw* la disaster, punched oat In appearance with clean out edgtelS sad a smooth hses with vary littls aserotis tieaoa ia connection* thi%^ steer eateated to the mails layer undermining the meoea sliehUy at -M^ that point* there wee a large amount of hlood ia the luaen of the toUtl tee tines in pylorlo and the three eaece* One ease had a snail of the ateaaoh reseobling the intestinal sloer near steers hat the mash wmm asaller la diaeetor* in the other eases the wooes of the stomach wasW^f:; normal* A; Iron both the symptoms observed ebon living and the patholog* leal findings. It is evident that wbsa lead tetra ethyl ia applied locally near or over the abdomen, the lead aots diraotly on tbs intes tine* producing acute lead oolio followed by sloeration sfclch may lead $-: to peritonitis* this eoafirwe the observations of Oiler eoweraing oases of eolia In ordinary lead poisoning which present the features of ' on seats intra-abdowinel inflammatory condition* ?-* t, .&\ *4? A'-X' % 4 - Wfc, . .. hOO^h ATPUCAflog* -Oswolstlvo sfteots* i tost was Jaade upon d doe weighing 4*0 IcUos, Spplying 0.1 eo. every twenty-tear hoars to s Shaved area upon the sheet, to ascertain the eumlafcivo sffoots of th# eompossd* :^;.*he.;first- ten 0*1 oo* ajsplioatioas did Mt sffeot the dog " .-ii f/W if*CKr#it'i'-Tjrij - t* 4*:' ry ^- ''?PV A 5h >' V ". v *c* f*- * },,f ^ ->1 ^ t ^ ^ .' % i,'-; ->.-</ -'. .- '''^V5v- -8- 1,^ " *` \i. * *" * " - *. , *. - 4 . .. 7.;u";'v-.77 w~tfeSg^E| appreciably. After the twelfth application the dog began to depression and occasionally aooe nervousness * After the eighteenth application the dog was aerxodly depressed also Very unsteady upon\y Its feet end the trembling of the' body showed taariced Increase. She^ trembling gradually increased until the twenty-first application had' been aede, the dog dying forty ainutes after* So exoiteneht van- r ^ noted. t' ^ ... ...... W . . - ... '.7- 77' ,7 W,7.; ac3bwAai(jB3 lutsssios.--^irad is#^ ere node by subcutaneous injection. Thepure compound was drawainto a hypo; dernic gyring# and injected under tho oAin of tho tnltaals... Sha res y '*-.r . -y--. suits fellow* -s Amount laiacteu " ............................^ 0.25 OO 10 grass -` Died 164 hours 0.1 00 bQO " n 96 .<*V dyaptonai The gyurotocs were similar to those noted under Xoo&l application. She area of injection after death appeared noroal. .* $rl\ S$ OUhCUTiihiSiCCS IliJiJJTXOH.--Cxioulative Sffeots.---Guinea Pigsij 0.01 ee. in pure olive oil injected evory twenty-four hours. Three guinea pigs were selected for this test. Care sa used to select pigs of tho same weight. 2h reoults follow* ..:. ^afflirt.iajag.Saft, aVerai-n walrht of nit; .01 .01 .01 .01 , : : <. '.- 01- . .01, .01 "... ;*u /*.. o; ' --u 640 grtms 640 H 640 M. f:1 r -j i' o/s 0/3 . 0/3 640 t< 0/3 640 640 640 640 It tl V* ` n ' .1 ' ^ '> J. r 4\ 1/3 */3 w- 1 ,,,J ?%*' *. 3/3 . 7 >i, ' , `r4-/'Ko,^.. :- .ajswr 'V' ,v' ` - `W? ^ ** y iV > .... / * *!. The first three injections did not appreciably affect^; the s , 3is hours after;itlie fourth Injection ono pig; ahowea -v ** s&rfcea body tremra,' while theother two- pigs wore a&rhedly _4oprood.;'5'f One pig died Sixteen hours after the fourth injection, hix hours after the fifth injeotion the second pig ma seised with body tryooro and diod after twonty; hours* t One pig survived for tho eighth injec- tion dying twenty-two hours after. ' There was no Merited excitement :-:S sotwi. ,v.. . ^ : : HE 0017711) ""**W ' ^ - " V^f*^ h ". jS4ten*-'1; ^ --:vl^V ; ' * ' '*-'* -. ' l>- - - :' -.^'V--t'*->v- .. .: -- " >$T' - ... lar\ . w--.- -' '-i < '* * ' '' " -.-$> ` ^w/"\ ...:/ ~ * .. ji -, *k... . ,-z- A- ' ' * `-i*'-* ~ ~ t's0 A\i X' *- '-<,,>'-*" , Sr UBJl YES0Q3 IWilSTlOH.--Dog** J* Fivo dogs wore used la thUN t*st - Fare alive U was used m diluent for the eoqpatnd* Site results follows . ,.- * 1V; .. 'f- ' manat Injected ratr itttt, WxMSA VV^s*. *altia ft 0.078 Died 14 hoars ^ :t o^t 2 '* I 0*011 r . s. s 0.0083 C *'.. ]4 - * g * ;x 'H* 886 'rt (delayed) vV,Pr , ^ 0*0086 ;^f**c,, U- *~>tv lived r "''tv; a1 tr''- < */ 'j '.- J The lethal polfit for latraTsaoas lajeotion for dog* Is plaee&p^ at *011 so* per kilo "body weight. : * *>>-^e aweotisast Pogi lajeeted latrareaoosly shewed alaost iaoediata and aeutted sjrHptcias fToa the osapoand* . Fite edaates after being i" jested there were sartsed tsritahing of the fooe and eyes, laohryaation, f the eyes and nose* and m^pld breathing, followed by mrfced ensite->|^| Meat lasting for one hear to two hours* Haring the first hour afterjiff the injection aniaals Tonited blood stained aseoas end diarrhoea was also prodaoed* the ejeotioa from the bowols however did not appear^ blood stained* The ejBltent nay have been oaased partly by oolio*^^ She etoge of oroitoswnt was followed by oollepee, the dog beooning v helpless with narked treahllng of the body and extremities until death* ZhaAh&TiOH*-ttiee* d naiober of teste were run on aloe by the oonUmoas flow method to determine the toxicity of the cocqxmnd by UAalati^m* Sen olnate es]>Qsures to a gas air nixturo of the .;' - oompouM were aade, five mice being used for each ooaoentration* -.She'^ll overage weight of the ciee was twenty grams. ; The construction of the WM ohanber will bo brand in rejrart B.A*ii.K.H. #11* She results followi ,- .i ,, , `jS ' >' 1T/ *\Vr?*r $ *1 V 4** , -10- "* A HE' oomu> ' +* A tr*'* - i'-" -a. Concentration jgtttg flftftth atjttrtttflgfttfa . 6.698 6.11 4.958 4.184 8.679 3.617 3.428 2.612 1.615 0.71 / 0/6 5/5 0/5 0/5 0/5 0/6 0/5 0/6 0/5 0/5 0/6 0/6 0/8 0/5 0/8 0/5 0/6 0/8 2/S The lethal consoatration for aloe by inhalation ie placed at ' 5.11 milligram* per liter. yt,:,. . Symptoms* She alee Mioeed activity while being exposed to flea air mixture of the compound. Upon removal froa the gas the alee were nuticedly excited. In the aaso of lethal doaee the ci tenant &ivo way to monteu. depression followed by oollapse, and death. ' <*' ISUU!?1M. Cumulative affects.--iiloe. Hico showed the ,.,#, cumulative effects of the compound. Sea sic were subjected to -:,:h C- cons actuations of 06 milligram* per liter for ten minute* ease - erory twenty-four hours, the cample being changed for each run. " \ " After the fourteenth run there was one death resulting from the oom-;' v pound. She fifteenth run produced two deaths,the nineteenth run one death and the twentieth run one death. She total number of experiments made was thirty-two, resulting in fir deaths from ton sdee used. She result a follow* ' vis:o:;;V\-.:yr.,.,v-V: r &-V-' ' - ` % -r v 'Vr -v.: : :,:;V v' - . . . - V v;^'V.>4>Vv,'^'t>/' :'::r ' ` ..: , mm:; -V; - 1 '-iwir-jT... -* '';5-^ / ' j .* - . ' -. ,' v;<&~U' ff V;: -U,V: -A. ^ * _ K E- 001V717 `"^Zf^'-r- '&<: i . n::' -Z .- _ isr** < * : , **;- ^ ,r --'- T-^* *> / " " f^v~? v `<rA'-ir-.' C-SVM 6-7-84 (Ml 6-10-94 4-11-9* (>U*M 4-14-9* 0-10-04 6-17-94 6-10-84 6-10-14 0-00-04 4-01-04 0-09-04 6-08-04 0-90-04 7-1-04 7-0-04 7-9-04 7-7-04 7-0-04 7-0-04 7-10-04 18 10 10 10 10 10 10 10 10 10 10 10 10 6 0*49 0*49 0*490 0*999' 0*497 0*479 0*400 0*400 0*401 0*000 0*408 0*9 0*900 0*47 0*000 0*040 0*404 0*004 0*040 0*004 0*040 0*479 0*419 0*0 0*480 0*497 0*494 0*069 0*009 0*081 0*890 0*004 Ao A oAo oAo Ao oAo 0/10 0/10 oAo o/io oAo o/io V- -- lAo V A 0/7 0/7 *A 0/0 0/0 0/6 0/0 0/0 0/0 o/o o/o 0/0 o/o 0/0 0/0 0/6 ,f r 4^ total water of ntM a4o woro 08* 2too atanfo ooroeamtian v ,; 0*0 atLlllgruao po* lifco**: tbo total 4otfco won ftvo OKI of ^Ck0^' taa aloo ooO* _ -* .S<'t 4' Bogmftana* fh* ayapUMO proOaood om tto o mo o o ihooe reordo* vv -14- z'-yJ- KE oor*r>o . ilili Potubollsan .' ,-:>p SI: -. >i'> - , ' . : ^Vp'vo'"- ::.-;- ;ySSS 'T'Pkt-p.;:'; mm'mm If wo assume, as 13 indicated by the symptom, that the toxicity of lead.tetru ethyl is due to the lead atax rather' than the entire molecule, a study oftho Metoboliaais of ospecial ^ Interest as showing a new form of scute lead poisoning. For wo are; dealing with a hij^ily lipoid soluble lead cos^'ound Which, la capable of akin penetration and which, furthermore,'!# ooapanativoly stable* It is prob&bl; tho only compound where acute lead poisoning follows absorption through the skin* , * In chrohio lead poisoning the skeleton of tho body hue been shown to bo the storehouse for the cuc^aratlrely large amount of 1c accumulated. In acute lead poisoning distribution is throughout body with the urino and faeces as the sources of elimination. 21J nation throu^i the fSaoooa takes place oven when absorption is through^; thu respiratory truct, probably by oxoretiop from the liver along wit the bile. A nu/ftber of analyses wei*e cade on organs from both dogs ani?f gulnoa pigs of which the Wot oxaafdo is the systematic atuuy of dog 1602 as given below hlii& W$i Weight 17.7 kgs. Given a skin u<pliaation of 0.20 00. lead tetra ethyl per kilo body weight, equivalent to 4.42 oc. or './TO;&5; f> 7,01 i&wB on. i,ufiiat 12. li3>_____ hays after tTrira Voluiae bead Uontant itaeces V. t. bead Content application oc. KS. gram mgs. 1 2 3 4 5 . 6 '. .7 ; . vv - 8 -.1 QQ . 330 S'.' 340 - 1W . 13b' 1Gb none . 260 2.04 1.32 1.03 o.a . O.6. 0.6 0.6. ... 3b ;b /,. ' :>/' r ' Ib.b l^jf .** ... . -:V.' SSS'S " '"ffgflg She dog was killed and autopsiod on the eighth day. 1'. -13- - ":.2 ' 1," - -.<> m 4-i- 00177-19 - L? JS * AX'r-f t i/ - - .fv? >* -, ,vit-is5&?4wA*-f^-,v- .hv&C >-r- (' r' -,, ;i>vc vnY.<`yA;.r v-?/+vaT*^lv^rsjaNst'vS*^N<-?T*4 '5M,,'4"a$r4s*ri^rJ -^llil - 'S, ^sys^ifeV^-rr* : _w%Lr#&. ' ? **:>** *fl* * * j*? Wafct of r ~3mitot ' t '"? Y-'< &C0 Oww - ,,r'M:'t>orew`4a graas^Ua*.- j W-;3bk iL brain JUm* Intestines, aoall Intestines, large Eidney T --.'/ ~,r<?.^ Skin, arm* of application v Spleen 'x*'M%&**s&i' TO h 0l$M moo ^ ij \ & aooo m ; _ Jf'600 , 4*2 .r">Ni&/? f 200 , * t' 26*2 * "* *wXlf' 1000 '* *Jsg M .i -?'}* ^mm^eh . wn * ` > y* , *|gyH It Is soon that approximately onefifth of all the load eppl) was found in organs and tissue representing one quarter tho total of tbs dog* She amountexcreted ws very small, amounting to only one per eent of the total applied* In a atusher of other animals that had resolved small doses tlias before being killed, in the analysis of their organs no trees lead v&o found* this would indicate that tbs Isadoras removed from; body tissues ud deposited, probably in the Skeleton* - j ~' iJluee the aasuat of lead ease rot od in the faeces and urine Tory saell, it is easy to understand how sooli aoounts of lead totre ethyl^ may have a oumulative action* > 2ho difforenoes in individual susoepti^^g bility to this cuualative action are probably to be esplainod at least partially by the different rates of excretion of lend by different indivjut-^ uale* It is evident from the very auall lethal dose by intravenous injobpl tion (0*011 co*J, that yeiry small omounts of lead in the oirsulating bleodtlv are productive of serious disturbance of the nervous system, end also have ^ a diroot effect upon the intestines producing lead colic or even uloer&tiont Shoes results of the scute action of lead are precisely similar to thsC^r-%! Symptoms of chronic Intoxication, except that they are such sere violent*"& L Air rS~~Vif-'. ,ir<$*"V>v5.J^pr-*c & V. L . <f- . . y$** ' -'S V, , *4 * -t* bit . >^i.*VV>p>-"s, s^-*r^- r''W "* -- ** *% t "-. * 0 ^: * f>W\ >-?}A - ^ - JW V*#'J " i v ".-N s M---i - - ;$S$5i *. S f* \ '> -14- V>SYs.v *`V' T` < ^C' ' * a KE ooi ij ( n .n * -CV" '. - r~` r > ,,*>&<* - *VSS^^ M: fV- 9*Bk*r***.> * t-Tnr>HVLAlHi Counteracting ths eftoote produced by tidal application* Chemical agents vara used to counteract tbs effects' produced by applying load tetrs ethyl to the afeltu ln tbeae a lethal dose was applied am the ohoaical .agents applied imedlatslfl, afterward* Hydroohlorio sold In strength* of 10& *& and pegjL were mod and found to fes valueless# Gslslnn Hypoehlorite v*a naed y both In the fora of * dry pander and panto and was found to have noj^ value* .... r The Vnlue of Solventa la laaovlntt I^adZatrs^Sihyl* A number of solvents vara used to remove the lead totra ethyl before a soffioieaU quantity to prodnse death was absorbed-'fey ths8kin* ln tho foil* experiments the asslnala used were guinea pigs* The amount of lea<y tetra ethyl applied was a soperlethal dose (1 oe*) Zk* resultsi follow* ' ' ...... &qrimnt #1 - Olive Oil 'v. Zw pig* werer cleansed with olive oil one ainute after application^ of lead totra ethyl* both piga died* '5 s ih^erloent #2 - Ordinary Soap and tater Zee pige were cleansed with ordinary soap and water ana oiaatsi after the application of load tetra ethyl* both pigs died* Experiment #3 - Zlnetare Green soap Two pige were olaanaed with tincture green soap and water one alnuto after application of load tetra ethyl* both pigs lived* Experiment #4 - Zinsture Green Soap Two pigs wore cleansed with tincture green soap ami water two minute* after ajvlioatIon of lead tetra ethyl* doth pigs lived* Experiment #5 - Zinctare Green Soap . Zwo pigs were oloansod with tincture green soap and water five minutes after application of lead tetra ethyl* Both pigs died* tr xperlment#6 - Kerosons Zwo pigs were cleansed with kerosene one minute after application of lsad tetra ethyl* Both pigs lived* V> ?v Experiment #7'* Keroaene Zwo pig* were Cleansed with keroaeno five Minutes aftur applica tion of lead tetra ethyl* Both pige lived. r.. Kyi -4-f-- 'V>r>^v '^?r>?:vv; r* w > ; - - ,. ,< * p. . \-%V' *'v vS# Jsi'aJ* f-iV-- ^ *C\' >'V.>.V *<r. V-i*4'* *-V'.'1- 'rvi.- jjxperiaent #0 - Kerosene followed by Tincture Orson Soap and water Tec pigs wore cleansed with kerosene which wasfollowed tgr . tincture green sosp and water ten ainntee after application of lead tetra ethyl* Both plgsHved* vr"-?:- / ;.w~<"v\cV''.. Am " - ^V- sxperimcnt #9 - kcroseasr followed by tincture Green Soap and Water Two pigs were cleansed with kerosene followed by tincture green soap and water fifteen minutes after lead tetra ethyl application* Both pigs lived* f* " ' "/ ' -- ,r , Kxporistont #10 Kerosene followed by Tincture green Soap and bator Two pig* were cleansed with kerosene followed by tincture greens soap and water twenty minutes aftor spjiioation flood tetra ethyl* Both pigo lived* :p fflq)riraont #11 - Korosone followed by Tizmtute Green 3o&p and Water Two pigs wore cleansed with kerosene followed ^y tincture green soap and water twenty-fito minute0 after application of lead totra V ethyl* doth pigs lived* Experiment #12 - Kerosene followed by Tincture Green 3oap and Viator Two pigs wero cleansed with kerosene followed by tincture green ^ soap and water thirty minute* after application of lead tetra ethyl*-'** One pig lived* One pig died* iuxporiiaont #13 - Kerosene followed by Tincture Uroon Soap and Water four pigs were cleansed with kerosene followed by tincture greenj^^6, soap and water. Two pigs were cleansed thirty-five minutes after exposure* Two pigs were oleanaed forty minutes after exposure* All^A^JIf four pigs died* / Gonelust am both olive oil wiO. oocnon soap and water proved valueless as agents to remove the lead tetra ethyl from the akin* <1. Tincture green soap was effactivo if used within two minutes after the application of the load compound. Kerosene proved to be tho betit agent tried* all pigs lived that ware kerosene treatod up to thirty , minutes. it was observed that the skin of the pigs teat were treated with kerosene alone became tense* interfering with the movement3 of the eniJmls. Tn^ skin would also crook and toar causing great discom fort* ` It was found that following the application of the kerosene by tincture green soap and water removed the kerosene leaving the skin soft end pliable* HE /-v ^ 1 VQlT^stf..; .JrfV'rirv '<TM*: t.- -16- /r-wv, S* yr'i. ., 'jS * > V\ . t ; . - - wA- - & S,, >>< rw >, ,/ - V*. .a ;K:y /v y ;w &: ` - *' ''* s. '',, **i.*1'.-VJr-J.;^. 'a^V . ..- . -Pv_-. * ^JA ; r*- - r,-'i \' - <RJ:; f;',^ Xt It quits orldent fro* these Observations that the ttemfuotoro, handling mi distribution of load tetr* Is v c It o o oonsldsnlilt danger to ptUvi of oouto load soiwtlaf la tooa# instances whom considerable tutorial i qpleshod upon the skin, v&# sad of ehronie load poisoning trm too absorption of anil anounto by inhalation, by too skin or fey couth* foot# fey too Bures* .of gg "jfvf ;,:' Mines appear to show that load tetra ethyl la eah&ast gases of $8 aaionobilos Is not toxic to oal^als haring been changed to Iwool* * able ftwa of lood ' v* *' " v V',i'4`i;:'4 > \ i: It is aot believed that this compound la of snyggreatV: value as a warfare agent feeoause of Its low toxioity as a Vapor, and the fhet that It decomposes at 12QC* Although splashes of this lipoid on too skin will prod&oo death, if toxioity for aaa is siailar to death of a toxioity far dogs it man* Shoe it could would require 21 oo* to cause hardly fee used as a spray for the mmm lethal effect although possibly a certain xuaber of essoaltiee eould fee so produced. MM WS&mm .5 * " ; *> i7-1*'* '> '---iT' ' ' Uj 'CV%V-i: - ^Mv/r-.^2-'> 5- --r -. |iy -5. -V* - 3 ^'-v%r-t i-l'ih 4 5*^ - > " ^ <V N~ t'*;5?t1-' < ". BubaiUed V* twwf&iAd[I ' / L-"' a A* Kldridga. JS>,?l^,>'f,*VW-'-> -V<.x * ^^ ^ ^ >r ` 4 "'*,<r ^-' 'V ^ V. , 1(,0v^'*.^ ` " x&~-' t s,'e~ihiSs,'ishvit 3ttporvIa*d lyi D. G. Vfoltan, Lt Quadra, Ii,Ca, U.G.K., Chief, Bep't# of 'foxloolcgya Approved fcyi r , , iJdsrurd ii. Yod-uwr, At a Cola, iC, CJ*A, V:: ' ' ' '?: % Chief, iiediObX ItaSefcreh Division* A Ctttdsr of tho Soxloit^Af tatf ---------- '" g"- -m,*iVt,v f* o ^ -> `*^1 Wor* fcegoxu hay 7, 1924 a Worn coopletedt Ootoher 6, 1924, ; ~<fr 4- ^ `A <A s ^iVy '*?*'> $** *- -^2?" i(8 < ** .'-rf* *--1 .. --' r ** f ~*w jAV * >> ^-' ='* * ^ JJ ^ ^ ^ V-*- , fclad` pn^iitAali amtmdcli)i ~ (oopiedi , 4fJ * t'i'-c *' ` > *W ^ ^ .* t ---- -s.^ -W^ .u'T?^a'Ca" >^ 'r-*j - *>-*'x^-'-'>. -'--- 1 -i. ^, j^, AAJw"' \ -K.;>; v' ^ v* ;.i ''T>asv.feAi'-1 7^-?'"--*'*,'- f j' -4>s>-SiS' ':Ar - '5.-il fc -I- \ Jrt ' \ >;* Kf - * / v-- -v- i.v i ^ A **it. ; -r ; y-.-a` *vAf - - HC^ V ". . *- * * `~*,v ; ^rS v f.