Document NNjq6Yar1m115J8Zgb7dBL28

Acute Inhalation Toxicity of Vinyl Chloride to Laboratory Animals E. MASTROMATTEO, M.D., A. Jl. FISHER, Ph.D., H. CHRISTIE, B.Sc., and II. DANZICER, M.D. Division of Industrial Ilygicnc, Ontario Department of Health, Toronto, Ontario; Department of Physiological Hygiene, School of Hygiene, University of Toronto, Toronto, Ontario; and Welland County General Hospital, Welland, Ontario Introduction scrib'd ns very slight. Elimination from the I FIRST prejiarod in 1833, vinyl chloride 1ms was very rapid. These authors quoted the Worj of ..Schaumann* with experimental animals. ] fire ctahonemdeperixonpdtlouosciintoiocnrneliaaoszfeodprodulsyoevf iitnnhyetlhmcehollnoaorsimdt edeerrcaeasndidnesi.tinsTheorcaortssiksaidwnndiethydoougdstamawnaeygreep.aabAthlecocltooogrdiecinnadgl uertveoidreeSnpcceheaatuoedf i liv narcotic properties on acute exposure arc well known. As an industrial material, however, it has been regarded as of moderate toxicity. A Thresh old Limit Value of 500 ppm was established by the American Conference of Governmental In dustrial Hygienists. Xo industrial fatalities associated with its use have previously been reported. It was therefore of special interest when two fatalities occurred in a plant handling vinyl chloride. This plant is en gaged in the polymerization of the gaseous mono mer with the aid of catalysts. One worker died while cleaning out a polymerization vessel and the other while working in a pit. Details of these two fatalities have liecn rc|sirted by one of the au thors.1 Published information on the acute toxicity of vinyl chloride to exiierimental animals proved scanty, l'atty, Yalit and Waite* in 11*30 re)anted on the acute response of guinea pigs to vinyl chloride. They found that exposure to 20 to 40 per cent- in air killed guinea pigs in a short time; cx|xnure to ten jx>r cent was emlun'd for several concentrations of seven to ten per cent ini; would lie narcotic to humuns in a short timer 12 per cent would be daugcrous. Vinyl chloride has been studied os a anesthetic ugent. Outer and associates* noted t incoordinated muscular activity of the extrarn}^ tics and cardiac urrythmias of a serious i w ere olwcn cd in all six dogs used in their expend merit. Curr and other*1 found that vinyl chloridfj produced sensitization of the myocardium-, three of seven dogs in which it was adminis as an anesthetic agent. Two eases of vinyl chloride gassing occurred iq :i factory in Great Britain where jxilyvinyl chlorr i<lc resin was Ix'ing made. These were reported byS the Chief Ins|X'ctor of Factories.1 In one esse aj process worker was standing outside a pohmeri-^ zatiou vessel and washing it with a water stream.^ After ten minutes of this he suddenly collspsedi across the o|ion manhole. Artificud resuscitation] was successfully applied. Sulisequcnt symp cx|H'ricnced lv this worker wen; tightness of the^ chest, nausea, alslouiinal pain ami headache. The ; hours. Congestion and <ilcaia of (he lungs with second case occurred in a maintenance worker , hy/ieii-mia of the liver ami kidneys were noti-d. who was overcome while repairing a vinyl chlorides Peoples and Leake* found the minimal anes- leak. Doth men were hospitalized. Another work4[| thetie range of vinyl chloride in mice excised for whose ha mis were accidentally sprayed ^itijj ten minutes was S to 12 jier rent in air; 25 to 30 vinyl chloride litjuid under jmwsurc developed aj |>rr cent was fatal in ten minutes. Dogs and rab burn. This latter ease was re|x>rted by Harris.^ bits were anesthetized within one minute when cxjxisfd to a concentration of alviut IS per cent in air. Recovery was very rapid with no apparent Such burns may occur with other highly vo materials when sprayed onto the hands SS s liq untoward effect even after prolonged anesthesia. under pressure. Lehmann ami Fluty* noted that vinyl chloride Filatova and (.Ironslx-rc'* in 1957 reported < was highly narcotic hut had a wide margin !*- hygienic conditions in a jxilyvinyl pn tween its narcotic and lethal concentrations. Its plant in the U.S.S.R. The jilant was engaged id local irritating effect ami its toxicity wen- de the iHilymerization of vinyl chloride bv means < 394 20546001 Industrial l :i catalyst. A centration of from alxiut 2< Threshold Ij Jl|0,l K A spa; - t illed in v I teen use o alstve it was lion studies i dally nvailab! for comjiarist information o cal changes in animal. Experimental Vinyl Chloi in a metal ey' gride with tl' gravity Wsiercontirni Bmtiaft nue *C Ilytirucm chlorit A<viyl*ne .\tv'altWliy<le 1`ure vinyl (cm|s*raturc; a sweetish <xV and its explo cent. It lias t; . t niinalx: 3 in the study, m the san mlard com nay. All wee K'luiptncnt was 50.G lite: window and : h-ascl in gavalve on the through com hinted J'isln'i l>y motor at n a meter. Tin iv cmnbitn class V-tutsing to the a continuing s Calculations ilucc tile foil chloride in ni cent. All com I n >rt ns per c, BFG03836 Chloride into, Ontario; o} Toronto, d, lination from the 1 hors quoted the wojj mental animals. Mia > endure repeated nd peal evidence of lira ding to Schaumsim > ten per cent in u] ns in a short time id rous. -M studied as a possifcffl associates4 noted thd tivity of the extrema s of a serious nature s used in their expert nd that vinyl chloridq the myocardium in h it was administered ile gassing occurred i vlicre polyvinyl chlorj haw were reported 1, tones.* In one case i g outside a [xilyraen , witli a water stre re suddenly collap, Vrtificial rcsuscitatic uhacquent sympt nrm tightness of in aiul headache.' maintenance worke airing a vinyl chlor iized. Another work ntallv sprayed wit pressure developed i reported by Harris.^ other highly volat i the liands as a liqu in 1957 reported polyvinyl processing riant was engaged cliloride by means o( Industrial Hygiene Journal 395 a catalyst. Air sampling was done and the conciitmtion of vinyl chloride was found to vary fputi about 20 ppm to about 315 ppm. (U.S5.R. Threshold limit Value: 1 mg/litcr or alrout 400 |)|iin). A spastic ty|>c blood vessel disorder was described in workers from tiiis plant. Itccnuse of the recent fatalities mentioned shove it was decided to undertake acute inhala tion studies in laboratory animals with commer cially available vinyl chloride. This was done both for comparison with earlier work and to provide information on the acute response and pathologi cal changes in more than one species of laboratory animal. Experimental Materials and Procedures Vinyl Chloride: The vinyl chloride wss supplied in a metal cylinder under pressure. A commercial grade with the following specifications wss used: SprciSc gravity it 30*C Watr mtMt Baling map *C nydrapo eUeri Arvtyltat Amaldohydt' Inm I'urity (par mat) Impuritfaa (parent) Koat -II to --tJ Nona 10 ppm nilnn SO ppm maaimui Hi maaimui 94 aiadM Pure vinyl ehloride is a colorless gas at room temperature; its boiling point is -- 13.9*C. It has a sweetish odor. Its flail point is given at --78*C and its explosive limits in air from 4 to 22 per rent. It lias the molecular formula CHj:CHCl. Animal*: Mice, rats and guinea pigs were used in the study. Test and control animals were taken :> the same laboratory stock. All were fed a Mandat'd commercial diet and housed in the same wav. All were of the same stage of development. Equipment: The inhalation chamber capacity waa 56.6 liters. It was equipped with a viewing window and an inlet tube. Vinyl chloride was re leased in gaseous form through au adjustalilc valve on the top of the containing cylinder, then through connecting rubber tubing and a recali brated Fisher flow-meter. Fresh air was pumped by motor at an adjustable controlled rate through a'meter. The streams of sir and vinyl chloride were combined at appropriate rates of flow by a glass Y-tube leading through further rubber tub ing to tlie animal chamber inlet, to deliver a continuing stream in the desired proportions. Calculations and adjustments were made to pro duce the following flow concentrations of vinyl chloride in sir for delivery: 10, 20, 30 and 40 per cent AH concentrations are expressed in this re port as per cent by volume in air. No determine- tions of vinyl chloride concentrations were done in the test chamlicr diving the experiments. Experimental Procedure!: Different groups of five mice, five nits mid five guinea pigs were placed in the chamber and exposed for thirty minutes to concentrations of 10, 20 and 30 per cent vinyl chloride in air. Simitar groups of con trol animals were maintained but not exposed to vinyl cliloride. At the end of thirty minutes ex posure the test animals were immediately re moved to fresh air. An .additional group of five guinea pigs was exposed to a concentration of 40 per cent vinyl chloride in air. In all 65 experimen tal animals were involved. Observations were re corded on the animals during and after exposure. The animals which died either during the ex posure or after a delay period were autopsied soon after death. Two weeks after the exposure sur viving test animals and controls were sacrificed by a blow to the head with the exception of four control rata which were killed by exsanguinetion. All animals were examined for gross pathologi cal changes. Tissues were removed from all ani mals for microscopic examination. The lungs, liver, kidney and heart were removed in all eases. The brain, adrenal, spleen, trachea, lymph nodes, and the eye were removed from represen tative animals in each group for study. The tissues were preserved in formalin and sections made for staining with hematoxylin-eosin. S|iecial stains were made wlicre indicated. Observations Control Animal*: No symptoms were exhibited by tlic 15 control animals and no deaths occurred. Ten Per Cent Vinyl Chloride: The response of animals exposed to this concentration is recorded below in summary form: Time Slight irriuuoo it into tad raU. Inertnerd motor activity Am it niter, tlsva nt tod fuiMk (tics. Inertafd motor Mtirity it tU tpaote; ivitefciag of titimitit it mica. Proaouaatd utmor, ttctctdy pit tod muMultr ioooordiaatioa it li eporiae. Miet tad rata it tide poaitioo; muoeuUr ienoordination, tmmamtad twitching of utnrnitm it guinea pip. Miet tod mu unwneeima. guiap pip try uatiaady but ttitt funding Miet tad mu it dorp aaraia; guinea pip ia tide poeitiot arHb tmmem cot Ex|x>eure was stopped and.the animals removed to frvsli air. All recovered within five minutes. Twenty Per Cent Vinyl Chloride: The response 20546002 ijilx v! ' El i : BFG03837 S9t; October of animal* exixwvd to this coneentmt i(>n is re corded licloiv in summary form: Ki|m\ik Time KcftpttnM.' | IiuinfdUlf irritation in min' anti rat* 2 Mtwrokr tiwMoniiiHkUoa in micr *nd nil. ft Mittind Wion theinifif* riurUI tnmonand twitWiin* of ihrntnmi' ta; tinatradinnM an<1 imwwutei innv ordination in fttiacn pin. 10 Mica and rata iineonariou* with rapid irracular breathing; ftiinea pit* tm- ponaeieu* but lioina mxknl t itcli in*. Ift AUuunMliiA drqt mmrii; rnpimkint ifTcnular and rafud. 20 He*)* narrow; bftwihinc fkwr and *lwltew. 1ft Breathin* mated in one mom**; frothint at mouth and nonirila in mica and rat*. 10 All animal* in deep nareoai*. Exposure wax stopped and tlie animals removed to fresh sir. Mice and rats recovered faster than the guinea pigs and appeared mimviti within five minutes except for one mouse which was dead. The guinea pigs continued to show muscular in coordination, unsteadiness on tln-ir feet until 21) minutes after removal front exixwure. Thirty Per Cent Vinyl Chloride: The re*|xmse of animal* cxpoAvl to this eoiu-entratiun is nvorded below in summary form: Expoaorv That (minuter) Rniamr Mior hoorni initsfiitn imtet]mte)y nd lie mta HanrH imialKrti 'injfWJy tfierraftrr. 1 Muentiaf incvurdinutioii in tuiee and rat*. 2 Mica and mis in *Hte jwwitinn iih marked tfuiiton and twitchitit l the mitmitin; muaeuter incoordination in fttiMn pin* with dovelopinc (aniy- *ia of Ota rtirrmiiWi. ft All animal* Mnanaacwm*; rapid irr***ljr ' r*lratinft* in mien and mi* wit)* farthing rIshi! wp Md itmmli; twitrliiM *d rMmuilies st II r<*ijr(Vd rac--ioo*Uy in luinva pin*. 10 Heapsration* *l<nHwi in mica: breadline tew and ahaltew in rat*; cninca {>* tilt rtMhiud orraaional tatirl.inc movement* of tls* rttrwiiiio. IS Rraothini Mopia-d in mu; r.*p>rtonr low and *hallow in anil*** pi**; twitching of enmnitin atill present in fuioa* pie*. 30 Mie* and rat* *till; *uinr* pi|ta in iWp Rarro*i* with alow lirraUiinc Exposure was stnp|H-d and the animals removed to fresh air. The mice and rats were dead. The guinea pigs took 25 minutes to return to their normal ap|>eaninec ami activity. One guinea pig from this group died within 24 hours following exjHamre. Ta iii.k 1 Niimlier of Deal Its in I tint-rent Group* of. Mire. Hats amt <0000:1 Pigs Kx|ki*c<1 for Minnies in Varying Concentrations of Vi Gliloridc in Air Vinyl rhhiridc ; 4 ontrni ration ipertenI by toiume in air) ID 10 3t<e> Tout | i Labnratory animal Mire <1/1 IS ft/ft -- 4/13 Kill Guide* pin 1 0/ft 1 C/ft 0/1 1 0/1 I/I j 1/4* -- ! i/i* */tl | J/W * A delayed denth occurred within14 home Idterif r Forty Per Cent Vinyl Chloride: Only five | pigs were cx|Miscd U> tills concentration. I irritatinn were immediately apparent. Mu ineoordinatiou ap)xativd within seconds. .') five minutes all the guinea pigs were uno witli slow shallow breathing. At tlie end of ; e.v|N)siire |x-ri<xl one guinea pig was dead end" remaining four were in deep narcosis. These' vivors tixik .10 minutes to return to their; npix-ar.mcu and activity, hut one died within: following 24 hours. The mimlicr of deaths occurring in diff grou|i# of hve lalxirutnry animals exposed^ thirty minutes to varying concentrations of i chlnridc in air is shown hi Table i. Pathological Findings Cross pathological ami histological studies! carried out. The findings are summarized 1 Control Animate: These animals showed: gross or microscopic evidence of damage. Ti n Fir ('nit Vinyl Chloride: All test anin survived this c\|sisurc. They were sacrificed two wicks later. On gross examination there was I deuce in mice of slight liv|>en*mia of the l1' Tliis was less marked in nits. Guinea pigs I no difTerenee from control animals. On his examination the mice showed very slight eng mint of tlie pulmonary vessels. One showed degenerative elumges in the tulxiltt . thelium of tlie kidney with hydropic swe Tlie nit* showed slight congestion of tlie espilh ies in the lung. Lungs in tlie guinea pig were < slight ly more hvix-n-mic than tlmse of the conk animals. Twenty Fir Cent Vinyl Chloride: One IDO died as a result of .1(1 minute* exposure to r comriitration. Pulmonary congestion was evid: on gross examination. Microscopically, there ' 20546003 Industrial Hygiene Journal 107 ,i :'rgement uf the blood vessels in tlm hint; with ji: : Iiv- areas nf atelectasis and minimal edema. Tin kidneys showed minimal degenerative changes in the epithelium of the convoluted tu bules. Tlw test animals surviving this ex|tosurc wore sacrificed in two weeks. On gross examination, oingest ion of the limes was |>rvscut in all *|tcctcti, lint it was inure market! in the tnieo and rats than in the guinea pigs. Histologically, there was oviili nee of pulmonary congestion in ox|Miscd aniie.Some fatty infiltration was present in tlic k i nf one rat. All other tissues studietf uppeared normal. Thirty IOr Cent Vinyl Chloride: Gross examina tion nf the animals which died as a result of this exposure revealed congestion of the lungs with hemorrhagic areas. The miir and rats in addition showed congestion of the liver and kidney. The Hie guinea pig death was delayed. In this animal there wits marked congestion of the lungs with hemorrhages and the liver was distended and very I'le. The microscopic changes in the animals v.:.a h died included marked engorgement of the nuiinonury liltsmI vessels with edema and hemor rhages in the lungs. The trachea of one rat showed -ii|erfieial desquamation of the epithelium. ConI'lstiou was also evident in the liver and kidney of the mice and rats. The liver of the guinea pig which had the delayed death showed severe fatty degeneration of the liver confirmed with frozen -- tions stained with Sudan Ilf. The four surviving guinea pigs wen* sacrificed t weeks later. Marked pulmonary congestion |irvseiit with hemorrhagic areas and edema, ft. "tie case there was evidence of seeondaiy bact' l i.tl infiltration. The liver in tltese guinea pigs iavr the ap|)ear.meo of fatty infiltration but no bit was demonstrated on frozen sta tion. I ort'i I'rr (O ut Vinyl ('hlnridr: One of five uinitea pigs ex|ised to this concentration died toI IIm the e\|Misiire and another died within 24 hours, The two width died showed marked con: ohm of the lungs with hemorrhages on grass initiation. This was also evident on micro 'll examination. The liver of one of these gave apiH'itniovc of fatty infiltration, hut no fat ' mhl Ijv demonstrated on frozen section. The three surviving guinea pigs were sacrificed tw.i weeks later. Marked congest ion of the lungs with hemorrhage was evident (Hi lioth the gross mid microscopic examination. In one guinea pig, tin- tracheal epithelium was completely alisent. radiological studies which were made of the ' 'am. heart, spleen, adrenals, lymph node* and eves showed no diffvrftiee Ix'twceu controls -I animals dying as a result of cx|MJ8ure or Ite- i ii ' ti controls and the surviving animals sacri- lived two weeks after ex|xixure. Them was a tendeney for the IiIikmI to remain unvlotted in the animals dying during fX|msurc. Tliis feature was noted in the two human fatalities mentioned ear lier hut it is not a sjioeifit: characteristic of vinyl chloride. Discussion Tlte rvs|smse of guinea pig* to inlinlatitm of vinyl eliloride was similar to that reported by I'nttv, Yant and Waite. Tlte guinea pigs in our study, however, tolerated a greater ex|Mi*ure dur ing tiie ex|x*rimcnta) jx-riod tluin either tlic mice or rat*. Tlte results in mice agracd closely with those tv|iorted by Peoples and Leake. Rats were similar to mite in their response. Tito pathological changes in animala which died a* a result of cx|iosure were mainly those of vascular engorgement of tiie lungs with hcinorrltage* and edema. Tlte severity of tltese changes varied with tlte severity of cx|touiv. In tlic higher concentration*, pulntotiary change was marked with severe damage to tlte tradHatl epithelium. Congestion of tiie liver mid kidneys also occurred in test animals. Tltese change* arc similar to those rv|K)rtcd liv Patty and uxWK'iatc*. Evidence of pulmonary congestion was still present in surviving animals sacrificed two weeks after exposure. Patty mid associates reported that such changes had disapitcttred in about eight days Degenerative changes in the tubular epitlielium of the kidney wen* noted in one mouse dying as a result of ex|xisure and in one mouse sacrificed two wta'ks after Itcing ex|tosed. Such changes, however, were iiiiiiiinnl and not shown by other animals in tiie group. One of tiie guinea pigs with delayed dentil fol lowing exposure showed seven* fatty infiltmtioti of tiie liver. Changes suggestive of fatty infiltra tion wen* ultscrvctl in other cx|nm*I animals but not confirmed by frozen sect it ms stained with Sudan III. Summery Sofia rate groups of laliorutorv aninmlx eoinprising five mils', five rats and five guinea pigs were cxjtoscd in an iulmlatioii eiiamber to concen tration* of 10, 20 and 30 ]>er cent vinyl chloride in air for 30 minutes. An additional five guinea |tigs were cxfxtsod to a 40 per cent concentration for a similar |teritsl of time. Tlic response by each of the three *|xries to these concentrations is noted. Iiihalatiou of these relatively high eoneentrations prtxhiccd uarvosis uihI death. Mice were the most suseeptibh* with guinea pigs considerably more resistant, llats were similar to mice in tlieir 20546004 39S October^, response. Exposure to ten |>cr cent vinyl chloride in air produced deep uurcosis in mice und nits but no deaths; 30 jter cent eonccntnitions killed mice and nits. Ex|x>surc of guinea pigs to 20 |)er cent produced deep narcosis; but three of five guinea pigs survived cx|>osurc to 40 |kt cent con centration. Animals dying ns a result of exposure were autopsied shortly after death. Survivors and con trol animals were sacrificed two weeks later. Gross pathological and microscopic studies were done and these findings arc described. The principal pathological changes in animals dying from exposure were congestion of the lungs with pulmonary edema and hemorrhages in some, and congestion of the liver and kidneys. Failure of the blood to clot was also observed. One of the time guinea pigs whieh died following exposure showed severe fatty infiltration of the liver. Survivors sacrificed two weeks after exposure allowed little difference from the control animals. Pulmonary congestion was still evident but liver and kidney congestion was not. References I. Dakuot.*. II.: Awtlmul Puiaawina by Viayt C inn ol Two Como, CaaaJ.aa M. Atmc. J. ST; I ISM). J. Patty. F. A.. W. P. Vast, axd C. P. Waits: Asolo ol Cuimo Pisa u Vopanol Soiuo Now riun--fc Compound* V. Vinyl Chloride, Pot. SaU JbS, ^ (Au--M JIM). S. Pcono, A. axbC. D. LSAirTht Aaastbolio j Vinyl Chloride, J. PktrmottltQt U: JSl (ISM). 4. Lnwuoi, K. B., 4 F. Flout: Tttittltn oml Mm /d--riel Stltroli, Timaaisled br E. Kite oad H. F.l Jr.. Wiiliono 4 Wilkim, Idiian (ISO). 5. Schacwaux.O.: Ciudby Lfc--, K. B. AadF.l A Onnm R. II.. C. J. Caul J. C. Kanart, jjnM. J. I tru: AMMimnin XXVII. Kama** with Vfaayi i Aotttkmttltor 4- MS (ISO). 7. Caw*. J., R. M. Bon--IPX. J. F. Vitcma, ak> J. C1 Ja.: Anwihwia XXIV. Chmdwt CaaaUtuti-- Ol ] aarba-- aad Cardiac Aa--liriljr. J. HoataOi Timor. 07: 1 (IMS).' I. Amtotl Mtomt tf Ikt Ctit/Intrmtm-f Fomtrim ftr t mi. Usd-- : H.MJ.O. CsmL ST71 (Manfc USD. S. Ha--*, D. K.: IMtb Piobla-- in tba Mass-- Un ol Ilaatiaa, Bril. J. tod. Mot. IS: SS< (1SS1). IS. Filatova. U.S,AmE.SCaaaaa--a:Hy^aaitl C--ditia-- ia Poiyriayl Cblocid* Tar Fhala. Oioi SS-O U--uary 1SS7). AbaUwrwd ia AU. tf IFarid I St (July Itti). Back Issues or AIHA Qvartekly TT'OP IS YEARS THE AIHA QUARTERLY was the publication of AIHA, then A- in JOSS it was changed to be tlie AIHA Journal with six issues per year instead of four. Now limitation of storage space is forcing us to dispose of all back issues of the Quarterly. For individual issues quantities on liand vary from a low of $ upward. All issues except March 1946 (Yd. 7, No. 1) and June 1950 (Vol. 17, No. 2) are available as we go to press. Some issues are reprinted without cover. The cost is $1.50 per issue ($1.00 each wlicn more than three issues are ordered) from Volumes 7 through IS. From 1940 io 1!MG AIHA Quarterly apiicaroil ax a section in Industrial Medicine and Surgery, Jiowcver these issues f these sections have been reprinted and are available as a unit. Tlie compete reprint, Yols. 1-7, costs $10.00 to members, and $50.00 to comjinnics or departments of government. Handsomely bound, complete sets of Yols. I--IS with cumulative index are available for $250.00 per set. Address all orders to: George D. Clayton, Executive Secretary, AIHA, 14125 Provost, Detroit 27, Michigan. (Back issues of AIHA Journal, 195$ to present, may be obtained directly from our publisher, The Williams k Wilkins Company, 42S E. Preston, Baltimore 2, Maryland, at $1.50 each issue.) 20546005 Acut WILL Depart Introduction THE element tlial Crookes in 1SC1 b and isolated chcmica Lainy. There, use no thallium ami its pro Tlie principal uses of t (o its rodeiitiekl.il pro; used as a depilating al-n used in the prod' optical glass and in tit ti*m counters. An examination of nimdxT of published r thallium toxicity folio cides containing thall sidcrablc amount of w the depilating action < lalxiratory animals ai intuition and cxcrcti |TI:**) has Ix-en re|iort i gators.*' * '* Risvntl; i-i-" have demonstrate containing sulfur act a.acute thallium |>oisonii Tlie work rcixirtcd b acute toxicity of tlialloi oxide (TO) follow ing t` coiii|miuiii1s to several : end mutes. The ingest |aninds was also in'".* ihnv moutlis. Experimental Methods The two thallium eoi taiued from the Amerii Co., Denver, Colorado ical Commerce, Newa acetate). The purity relatively liigli (111).5-9 Tliit itapK u> Ik0 oo wot lie.. I'nitfd St\*m Atntnir Ene Itochwitr Atomic Kouny I