Document gaGbV5jzLdkNzYQMpMQ13NGp9

Acute Inhalation Toxicity of Vinyl Chloride to Laboratory Animals R&S 028156 E. MASTROMATTEO, M.D., A. M. FISHER, Ph.D., H. CHRISTIE, B^e., and H. DANZICER, M.D. Division of Industrial Hygiene, Ontario Deportment of Health, Toronto, Ontario; Deportment of Physiological Hygiene, School of Hygiene, University of Toronto, Toronto, Ontario; and Wetland County General Hospital, Welland, Ontario hircdwction scribed as very slight Etir...nation from tbs body FAnarercItothRoaoemtSdicepTerpixonpprdtorloouepspceiinatoricortnkerneadhaoesoifenandprdo1au8lscyo3euvf3tiite,nnhyveetlihxnmcpeyhoolhlnsououcrirhmtdeledoeaerrircrdeaeaneidndweh*iea.tinelslTheoccorwaoorfastnSssiksccaievdhwnenandtriuretyahmydtoroiaaougdnnpstansidma*w.onwaeTyfgrietheshpe.eaasevbAteehxlecnpoacelutootorotgirhmdieoctiennraasndglntueqartvpuleoiaeodrnrteeeSinmpcdcceehaeatnalhsttouee.mdfiMnwlaniivnocaaenerrikrr,, known. A* on hduatrial material, however, it haa keen recorded as of moderate toxicity. A Thresh old limit Value of 800 ppm wee established fay would be narcotic to humane in e abort time end 12 per cent would be dangerous. Vinyl chloride has been studied ss * possible the American Conference of Governmental In dustrial Hygienists. anesthetic agent Osier and asmeiates* noted that incoordinate muscular activity of the extremi Ho 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 'he polymerisation of the gaseous mono mer with tbo tad of catalysts. One worker died while desiring out a polymerisation vessel and the other while working in a pit Details of these two fitsSties have been reported by one of the au thors.1 Published information on the acute toxicity el vinyl chloride to experiment animals proved manly. Patty, Vent and Waite* in 1030 reported on the acute response of guinea jugs to vinyl chloride. They found that exposure to 20 to 40 per cent in air killed guinea pig* in a short time; exposure to ten per cent wee endured for several hours. Congestion end edema of the hmgs with hyperemia of the liver and kidneys were noted. Peoples and Leake* found the minimal anes thetic range of vinyl chloride in mice exposed for tar minutes was 8 to 13 pier cent in air; 25 to 30 per cent was fatal in ten minutes. Dogs and rab bits were ancsthetiscd within one minute when ties and cardiac arrythmiss of a serious nature were observed in all six dogs used in their experi ment Carr and other*7 found that vinyl chloride produced sensitisation at the myocardium in three of seven dogs in which it was administered aa on anesthetic agent Two cases of \inyi chloride gasung occurred in a factory in Greet Britain where polyvinyl chlor ide resin was bring made. These were reported fay the Chief Inspector of Factories.' In one case a process worker was standing outside a polymeri sation vessel and wishing it with a water stream. After ten minutes of this He suddenly eoDopsed across tbs open manhole. Artificial rewocitetion was successfully applied. Subsequent symptom experienced fay this worker were tightTM-- of the chiat, nafrjea, abdominal pain and headache. The second case occurred in a maintenance worker who wws overcome while repairing a vinyl chloride leak. Doth men were hospitalised. Another woctax whose hands wore accidentally sprayed frith vinyl chloride Squid under pressure developed a bum. This letter ease was repc.*ed fay Harris.* caponed to a concentration of about 18 per cent Such burns may occur frith other highly volatile in air. Recovery was very rapid with no apparent materials when sprayed onto the hands os a liquid untoward effect even after prolonged ancathrsia. underpressure. . Lehmann and Fluty* noted that vinyl chloride Filatova and Gmnahnjt1* In 1957 reported on was highly nan-otic Iait had a wide margin Iw- bygirnie conditions in a polyvinyl jiroMSMog tween its nan-otic and Ictlm! mnrrctmtions. Its plant in the U5M. The plant vs rntctgcri in local irritating Wfivt mu! its toxicityere de the ladyiiHiriiation of vinyl cldoridu liy mcau of /mhittrial Hygiene Journal 395 :i catalyst. Air sampling was done and the eoni-cntration of vinyl chloride ww, found to vary from about 20 ppm to #lout 315 ppm. (U.S.S.R. Threshold Limit Value: I Ji.g/liwr or about 400 ppm). A spastic type blood vessel disorder was ilosenix'd in workers from`this plant. lkeaiuv of the recent fatalities mentioned above it was decided to undcrfchc acute inhala tion studies in laboratory animals with commer cially available viny 1 chloride This was done both fur ramimrisoa with earlier work and to provide information on the acute response and pathologi cal changes in more than one species of laboratory animaL Experimental Material* and Procedures Vinyl Chloride: The vinyl chloride was supplied in a metal cylinder under pressure. A commercial grade with the following specifications was used: EptdS* *aiSr a* VC W.ut --Ini BiOLiia*.*C BfOnmn tUaUi MtM A/Hsllhkyrk Im raWr (par c**0 lapadSi (par m&O I.SW.SI Naaa -11 to -tJ Noh EaaatWaj bea baa Si aaiteaaa |,| pulBB Pure vinyl chloride is a colorless gas at room temperature; its boding point is -- 13.9*C. Ithas a sweetish odor. Its flash point is given at --78"C and its explosive twita in air from 4 to 22 per cent. It hat the molttulsr formula CHi'CHCL Animalk Mice, rata and guinea piga were used in the study. Test and control animals were taken from the laboratory stock. AH were fed a standard commercial diet and housed in the same way. AH were of the mme stage of development. Equipment The inhalation chamber capacity was 541.6 liter*. It was equipped with a viewing window and an inlet tube. Vinyl chloride was re leased in gaseous form through an adjustable valve on the top of the containing cylinder, them through connecting rubber tubing and a recali brated Fisher flowmeter. Freeh 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 glam Y-tube leading through further rubber tub ing to the animal chamber inlet, to deliver a continuing stream in the desired proportions. Calculations and adjustments were made to pro duce tl>e following flow concentrations of vinyl chloride in oir for delivery: 10, 20, 30 and 40 per cent. All concentrations arc expressed in this re port as per cent by volume in air. No determina tions of vinyl chloride concentrations were done in the. test cluimhcr during the experiments. Experimental Procedurea* Different groups of five mice, five mts and five guinea pip were placed in the chamber and exposed for thirty minutes to concentrations of 10, 20 and 30 per cent vinyl chloride in air. Similar groups of con trol animals were maintained but not exposed to vinyl chloride. At the end of thirty minutes ex posure the test animals were immediately re moved to fresh air. An additional group of five guinea pip was exposed to a concentration of 40 per cent vinyl chloride in air. In all 65 'ixperimesta) animals were involved. Observations wexe re corded on the animals during and after exptmre. The animals which died cither during the ex posure or after a delay period were autopried soon after death. Two weeks after the exposure sur viving test animals sad controls were mcrificed by a blow to the head with the exception at four control rats which were killed by exaangumatioa. AH animals were examined for gross pathologi cal changes. Tissues were removed from all ani mals for microscopic examination. The hmp, liver, kidney and heart were removed in all cases. The brain, adrenal, spleen, trachea, lymph nodes, and the eye were removed from icpiweatative animals in each group for study. The tissues were preserved in formalin and sections made few staining with hematoxylin-eoam. Special staina were made where indicated. Observations Control Animate: No symptoms were exhibited by the IS control animals and no deaths occurred. Ten Per Cent Vinyl Chloride: Tin ireponae of animals exposed to this concentration is recorded below in summary form: ctolnltoltoatai r Mttfttr la <g i MtiahUi MaiatnUliSai XiaiaSaM aawaaS nry maMi)j balto Maul na to to* tuntoUda Ptothawith t Exposure was stopped and the animals removed to fresh air. All recovered within five minutes. Tueniy Per Cent Vtayf Chloride: The response r &S 028157 R&S 028158 R&S 028159 9 Acute Inhalation Toxicity of Vinyl Chloride to Laboratory Animals E. MASTROMATTEO, M.D., A. M. FISHER, Ph.D., H. CHRISTIE, ILSc., and H. DANZIGER, M.D. Division of Industrial Hygiene, Ontario Department of Health, Toronto, Ontario; Departme-d of Phynotogieol Hygiene, School of Hygient, Univertity of Toronto, Toronto, Ontario; and Welland County General Hotpital, Welland, Ontario ' ktreducHon scribed aa very slight Etiolation from the body THIRST prepared in 1833, vinyl chloride has 3. come into increased use in the lost decade in the production of polyvinyl chloride resin*. The fin and erptypnn hasard of the monomer and it* narcotic properties on acute exposure an well known. As an industrial material, however, it ha* beta regarded as of moderate toxicity. A Thresh old limit Value of 600 ppm waa established by the American Conference of Governmental In dustrial Hygienists. was very rapid. These authors quoted the work of Schaumann* with experimental animals. Mice, rata and dogs were able to -i>dure repeated nar cosis without any* pathological evidence of liver or kidney damage. According to Sehaumann, concentration* of seven to tan per eent in air would be narcotic to humans in a short *" and 12 per eent would be dangerous. Vinyl chloride has been studied as a possible anesthetic agent. Oster and associates1 noted that No 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 hi 'he polymerisation of the gaseous mono mer with tho aid of catalysts- One worker died while deaumg out a polymerisation vireel and the other while working in a pit. Details of these two fatalities have been reported by one of the au thors.1 ineoonfinated muscular activity of the extreme, tire and cardiac arrythmiss of a rerions nature were observed in all six doge used in their expert, ment. Care and other*1 found that vinyi chloride produced aenaituation ot the myocardium m three of eeveu dogs in 'vhich it was administered a* an anesthetic agent. Two ease* of-vfoyl chloride gassing occurred fat a factory in Great Britain where puljiiuyl ehlorWe resin waa being made. These were reported by Published informatics! on the acute toxicity of the Chief Inspector of Factories.1 In one n vinyl chloride to experiment*! animal* proved process worker was standing outside a polymeri canty. Patty, Yant and Wane* la 1930 reported sation vessel and washing it with a water stream. on the acute respoesa of guinea pigs to vinyl After ten minutes of thk Se suddenly collapsed chloride. They found that exposure to 30 to 40 pm cent in air IdOcd guinea pigs in a abort time; exposure to ten per eeat was endured lor several hears. Concretion and edema of the lung* with hypemnia of the liver and kidneys were Doted. across the open manhole. Artificial resuscitation was successfully applied. Subsequent symptom experienced by this worker were tightness of the chest, names, abdominal pain and headache. The second care occurred In a maintenance worker People* and leaks1 found the minimal ro thetic reace of vinyl chloride far mice exposed for - who wa* overcame wfaDo repairing a vitrei chloride icak. Both men wrre hospitalised. Another worker to minutes waa 8 to 13 per cent in air; 35 to 30 whore hands were accidentally sprayed write per eent was fatal in ten minutes. Dogs and rob- : vinyl chloride liquid under precrarw develop a beta were sncrthetUcd within unu minute when burn. This latter care waa repc.ted by Harris.* expoeed to a concentration of alxnit 18 per cent Such fauns may occur with other highly volatile hi sir. Recovery waa very rapid with no apparent material* when sprayed onto the hands as a liquid untoward effect even after prolonged aarethrsia. under pressure, Lehmann and Fluty4 noted that vinyl chloride Filatova and Crnuahcrg1* in 1057 reported on was highly nairotic t>ut liad a wide margin *- hygienic conditions in a polyvinyl pcnrcMng tween its narcotic and Irtlutl .'<n<w.tmtions. Its jdnnt in the UiSii.lt. The plant was engaged in local irritating effect aiul it* teixkiQT^keic de the |wlyiiicrifatitiii of vinyl dduridu by mcaia, of R&S 028160 Industrial Hygiene Journal 395 :i catalyst. Air sampling was done and the con centration of vinyl chloride wai found to vary front about 20 ppm to ulxiut 315 ppm. (U.S.S.R. Threshold limit Valui*: 1 n.g,liter or about 400 ppm). A tf|w*tic type blood vessel disorder wot ilcscritx'd in worker* from this plant. lieemiHo of the recent fatalities mentioned nbove it was decided to undertake acute inhale* tion studies in laboratory animals with commcr* itolly available vinyl chloride This was done both for rom|ioriaoa with earlier work and to provide information on the acute response and pathologi<~.il cliangc* in more than one species of laboratory animal. Experimental Materials end Procedures Vinyl Chloride: The vinyl chloride was supplied in a metal cylinder under pressure. A commercial grade with tire folicwing specifications was used: Spntt* tnwttr * ICC SitnmM td'snisi'C Britms-- shtoiSs 1 A.xgt-- Anliiatllk Inn Fo.tur (pwemt) lmfnitfai (par !> -11 to -*X Km II ptm Mian Mops nulmWB Ewrnktr fcaa in* KiMlam Uoniam Pure vinyl chioride it a colorless gas at room temperature; Ha boding point is -13.9*C. It haa a sweetish odor. Its Astir point is given at --78*C and Ht explosive Hmita far air from 4 to 22 per cent It has the molecular formula CHi:CHCL Animal*: Mice, rata and guinea pip were used in the study. Test and control animals were taken from the same laboratory stock. All were fed a standard commercial diet and housed in the tame way. All were of the some stage at development Equipment: The Inhalation chamber capacity was 50.6 liters. It was equipped with a viewing window and an inlet tube. Vinyl chloride wea re* leased in gaseous form through an adjustable valve on the top of the containing cylinder, thm through connecting rubber tubing and a recali brated fisher flowmeter. Fresh air was pumped by* motor at an adjustable controlled rate through a meter. Urn streams of air and vinyl chloride were combined at appropriate rates of flow by a glare Y-tube leading through further rubber wr ing to the animal chamber inlet, to deliver a continuing stream in the desired proportions. Calculation* and adjustments were made to pro duce the following flow concentration* of vinyl chloride in air for delivery: 10,20,30 and 40 per cent. All concentrations are expressed in this re port as per cent by volume in air. Xo determina tions of vinyl chloride concentrations were done in the-tent chamber during the experiments. Experimental Procedure*: Different groups of five mice, five nits and five guinea pigs were placed in the chamber and exposed for thirty minute* to concentrations of 10, 20 and 30 per cent vinyl chloride in sir. fiimilar group* of con trol animals were maintained but not exposed to vinyl chloride. 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 *.'165 'txperimental animals were involved. Observations were re corded on the auiraal* during and after expwqra. The animals which died cither during the ex posure or after a delay period were autopskd noon after death. Two weeks after the eipoecre sur viving test animals and controls were sacrificed by a blow to the head with the exception of feur control rata which were killed by exsanguhretion. All animals were examined for gross pathologi cal change*. Tissues were removed from *21 ani mals for microscopic examination, lb* lungs, liver, kidney and heart were removed in all case*. The twain, adrenal, spleen, trachea, lymph node*, and the eye were removed from represen tative animals in each group for study. Tbs times were preserved in formalin and sections made tar staining with hematoxylin-coom. Special stains were made where indicated. Observation* Control Ammole Xo symptoms were exhibited by the 15 control animals and no deaths occurred. Ten Per Cent Ffeyf Chloride: Tba response of animal* exposed to this concentration ia recorded below in summary form: t SifU irrfulaa* ia mim aad s x-jmoi mom --MiUy lm tom bto torn migotmm elm. M MumarnialMehtlw wtukta* r mmm m aha. IS rstft* SO r*U to mdrn pamOtm; mmmto liiiimTl--U IimhwI WillSUre KtealnU may It XauTnato ptmla to yniM whh Exposure was stopped and the animals removed to fresh air. All recovered within five minute*. Twenty Per Cent Vinyl CUtride: The response S96 October, I960 of animats exposed to this concentration is re corded faclow in summary form: (!<) 1 Iwietiu iniUUos la silo sad nu Momkr Iswdisatiaa Is mis* *d I )0<issd nil ca Uwlraldra wttk msrksd tnwssad tsiteWsa at tbs atnmlMs; mStdiM iW snln lam- wdlssttas Is (slsts pifM Idas sad imts imiwinn witk rapid Imsshr tmdiac tilaa pirn aosaataa b<it ahswiac iwkad twitek- --1--*-*- r ~ --1 Imwtdsr asd rapid. Daap sanaaia; kraslhlas aknr aad ahak law. m BaalNac aaaaad la oaa awiaa; Intblas aiaasth aad aesUilt la nka aad lata. m AO aalaiak la daap manoaia. Exposure m stopped and the animals removed to fresh air. Mice and rata recovered faster than the guafea pip and appeared normal within five minuted except.for one mouse which wea dead. Tbs pine* pip continued to show muscular in coordination, nnatmdincas on their feet until 20 minutes after removal from exposure. TAtrip Pm Ctnl Vinyl Chloride: The response of animals fRinunl to this concentration is recorded below b summary form: tSMMlISt (adaataa) -........... -- MHSrhs.sd brlWUss ImJsufr aad aksssd Mtaltos enfektr Tablx I Number of Deaths in Different Grou;** ni Kivc Mice, Rats and Guinea Pigs Exposed for Thirty Minutes to Varying Concentrations of Vinyl Chloride in Air Vhyl tkfarMs (SsnstrMfas tsInLrwctnistWsb) LtiwitMJ filkll Mia Met, CnlsM * Tarsi It SI IS Tstal s/s V* t/s S/S s/s s/s -- f/ll s/ir C/S S/S 1/1* s/r s/ e/is l/IS ii/ s/s ivm * A dthyaddistil anurrill witkjalUauralaMawtaS' Forty Per Ctnl Vinyl Chloride.- Only fire pnnea pip were exposed to this concentration. Signs of irritation were immediately apparent. Muscular incoordination appeared within seconds. After five minutes ail the guinea pip were uncouacsouu with slow shallow breathing. At the end of the exposure period one guinea pig was desd Sad the remaining four were in deep narcosis. These sur vivors took 30 minutes to return to their normal appearance end activity, but one died within the following 24 hours. The number of deaths occurring in different groups of five laboratory animals exposed for thirty minutes to srying concentrations of vinyl chloride in air is shown in Table I, I MWsshr lasowArafsa la ailaa aad t Idea asd as la aids padilna with Slim twam aad UrtlcHss l tks nSl-ltlll, aiuillrtit lamiaiMaatias la (alSaa plsawltk darrlopiat psisljralasl Iks aiiinaHUi. I an aalwk aaaaaadaat; rapid Inapdar mpeaOaaa Is ala aad raw ntt I ii IWblij at sstwltim U1 attanad aa--Wsatr la aiders pto. M NarakaUasa Mapped ta nics; knsthiac Wnr asd akaTina La rata; aniaaa pia> stu aaWHlad ill-iassl twilaklW WawaaaW al Ika aalnailUia. IS exalklas arappid la rm nulntlm aalawOws-^B.a^Sandm v_Sakm^alaamwtw_laEivdaaapnpimta- ; knlaaila IS Has aad raw aUB; nisi* piaa la daap aataaWa wtik Worn akalaw knstklsc Exposure wa* stopped and the animals removed to fresh air. Hie mice snrl rats were drwL The guinea pigs took 25 miuiiUw to return to their normal appenranec ami activity. One guinea pig from thi* group rlietl within 24 hours following cx|vimirv. Pathological findings Gross pathological and histological studies were carried (Hit. The findings are summarised below. Control Animal*: These ortHols showed no pom'or microscopic evidence of damage. f Per Cent Vinyl CUorife AH test survived this exposure. They were encrificed tea weeks later. On gram examination there wha evi dence in mice of slight hyperemia of the lungs. This was Ins marked in rata. Guinea pigs showed no difference froa\'tbntrol animals On KUtotogie examination the mice showed very slight crigorgement of the pulmonary vemris. Oak mourn showed degenerative changes in the tubbier epi thelium of the kidney with hydropic swelling. The' rats showed slight congestion of the capillar ies ia the lung. Luhp in Use guinea pig were she slightly more hypemnic than those of the control animal*. Twenty Per Cent Vinyl Chloride: One nar dial aa n result of 30 nunutre rxpraaire to this concentration. Pulmonarycringesthm was rvkkrit on gnaw tra mutation. Mirnwropivnily, Uhtv was H. Industrial Hyijienv Journal 39? miiiirpiiii'iit <*f Hit' Muml ill tin: lung with ficed two weeks after r\]nmire. T1\*re was a ;irv:ii nf nti-k-i-tasi* and minima* ixlcm*. triidfiii y for tin* Mood to remain imrloitcd in the /lie kiilmys tJimved minimal degenerative animal* dying during rxiwuiv. T'v.* feature was rltanciw in the e]>:tlnl'um of the eonvoluted tu- notiil in tlic two human fatalitkv mmtHUKv'. w- IhiIiti, IL'r but it is not a specific chs recti rirtic of vinyl Ti- test miimal.i surviving this exposure were chloride. snirifici'il in two weeks. On gras examineion, n nicest inn of the lungs was present in all spci ics, Discussion hut it was nuin* marked ir. the mice and rats than in tlM* guinea pigs. Histologically, there was **vi,len.v of pulmonary congestion in exposed ani mal*. Some fatty infiltration was present in the liver of one tat. All other tissues studied appeared normal. Thirty Ptr Cent Vinyl Chloride: Gross examina tion of the animals which died ns s result of this '\|vure revealed congestion of the lungs with liemoRiiagie areas. The mire and rets in addition showed congestion of the liver and kidney. The one guinea pig death was delayed. In this animal tliore ass marked congestion of the lungs with hemorrhages and the liver was distended sod very friable. The microscopic changes In the animals which died included marked engorgement of the pulmonary blood vessels with edema and hemor rhages in the lunga The trachea of one rat showed superficial desquamation of the epithelium. Con gestion was also evident in the liver and kidney it the mice and rets. The liver of the guinea pig which had the delayed death showed eevere fatty degeneration of the `liver confirmed with frosen sections stained with Sudan III. The four surviving guinea pigs were sacrificed two weeks later. Marked pulmonary congestion was present with hemorrhagic areas and edema, lu one esse there was evidence of secondary bac terial infiltration. Toe liver In these guinea pip Kara the appearance of fatty infiltration but no fat was demonstrated on frosen section. Forty Fee Cent Vinyl Chloride: One of five guinea pip exposed to tins concentration died during the exposure and another died within 34 hours. The two which died showed marked con The response o.' guinea pip-to inhalation of vinyl chloride was similar t,; that reported Dy Patty, Vast and Waite. The guinea pip in our study, however, tolerated a gTMater exposure dur ing the experimental period than either tho mice or rats. The results in mire agreed rlowly with those reported by Peoples and Leake, stats were similar to mice in their response. The petbological chas.-es in which died as a result of exposure ware mainly these oi vascular "ngoigement of the limp with h mar. riiages and edema. The severity of these changes varied with the severity of exposure. In the higher concentretioos, pulmonary change was masked with severe damage to the tracheal (pilMisa. Cooge-.tion of the Ever and kidneys also occurred in test animals. These changes are rimiiwr to those reported by patty and associates. Evidence of pulmonary congestion was still present in surviving animals sacrificed two weeks after exposure. Patty and associates reported that such hangre had disappeared in about eight days Degenerative changes in the tubular epithelium of the kidney were noted in one moua. dying sa a result of exposure and m one mourn mcrifieed two weeks after being exposed. Such changes, however, were mtwhwi and not shown fay other animals in the group. One of the guinea pip with delayed death fol lowing exposure showed severe fatty infiltration of the Ever. Changes sngpstive of fatty inUltra, tioo were obamved in other exposed nnhmJa but not confirmed by frosen sections with Sudan III. gestion of the lunp eitfarbemorrhaps on pm examination. This was-abo-evident on micro- Summary srnpic examination. The User of one of these pve - Separate groups cf laboratory animals com the appearance of fatty infiltration, but no fat prising five mice, five rets and five guinea pip could be demonstrated on frosen section. were expowd in an inhalation chamber to concen The three survrving guinea-pig* were sacrificed trations of 10,20 and 30 per cent vinyl chloride two weeks fatter. Marked congestion of the hup in air for 30 minutes. An additional five guinea with hemonhap was evident an both the gras pip were exposed to a 40 per cent concentration and microscopic examination, hi one guinea pig, for a similar period of time. The rcvpouao byeach tin- trurheal epilhdhnn was complctelyabsent. of the three spceice to three coaccntratinm is Pathological studies Which were triads of 'the noted. lmtin, heart, spleen, 'adrenals, lymph nodes and Inhalatioa of them relatively high concentra tin* eyes diowed no 'difference between controls tions produced narrows and death. Mice were the ami animals dying as a'resultof exposure or be- - most MMcrptiblo with guinea pip considerably twivn runtrnia anil the surviving animals sacri more resistant Rata were mmOar to mice in their 33 U) o to oo -a O to i 898 October, *2(10 nipniin Exposure to ten per cent vinyl ohloride is sir -produced deep nareoeia in rake end rets bat no deaths; 30 per cent concentration! lulled mice and rata. Expmure of guinea pip to 20 per oeat produced deep nercoaia; but three of five guinea pip survived expoeure to 40 per cent conomtratidii. *"dying as e remit of expoeure wen shortly fter death. Survivon and con trol anhniU m sacrificed two week* later. Qna pathological and microscopic studies wen dooe and theee findinp an described. The principal"pathological changes in animals dying from expoeure wen congestion of the lungs with pulmonary edema and hemorrhages icTsome, and congestion ef the liver and kidneys. Failure of the Hood to dot was also observed. One of ths tinea guinea pip which died following exposun showed acme fatty infiltration of the liver. Bumtop sacrificed two weeks after expoeure showed fitUe difference from the control animals. Puhnreiery congestion was still evident but liver and kidny congestion was not. References | L Dcamss. g.: JmSmUml r I I | by TM Ctesrffc; pert <( Tss Ckm, CWmMm JM. iM /. m in (am HM) I - a rim,r.A.W,r.Tm,irt&r.Vn:tMalUsaB S(MwnpSVir)IIH>tfairOiiHMOrtrt Omapess* V. Vtavl CttsU* JM, OmM JUpL U: M UsrtlM)a rma,aal>C.D.LaDtnaAirtMiPkia YrtriCMw^/. w--.np sanrqpa a Lnurn. ta,sr. lima fiMpmSIrtwr hMuaanrtiMUrtSranurt4i.r.Ma Jf.waaw AtWMssfcWtaiiiiOSP. a Snmma.0.:QuAby T iW--, a Srtr. Ttmj. a Omn. aa,C.J. Cim,1. C. lung, ASS M. J. naBu^s: ^AJmMMSas,k|||XMXVMH. Niaadi wttk Vhjt OMa T. CmsJ,l.SaBuinmi.aF. VM. Aia&bup wtai art CUAh AWmSillr, J. ftrm. mtd Apr. nMsmiiwa aas--ifcpirtsnwqarrwprtkr^pw^fa^ibr^ I$n, Lm4m : HJCa.O. Cmd. ST71 atwrt ntn. a Ifissm. D. Bllh NMwi Is k* a.rtn.i M* VaSIMaa/.MIUNtai(Bn. la ISiwn, V. a. w X. a Ohmm InWi WrtUac CSm Wliw Is WHul CMwHi ter IWrts OUOss pp. as Obmu am. n iia # ru n<a n dstpiim. /. Baca Issues or AIHA Qdmrib.t FDR 18 YEARS THE AIHA QUARTERLY was the publication of AIHA, then h 1898 it was changed to be the AIHA Journal with six ismes per year-instead of four. How limitation of storage space is forcing tu to dispose of aS hack issue* ef tkaQiartedy. Wot individual issues quantities on hand vary from a low of 8 upward. ABimnea sxcept March 1948 (VoL 7, Ho. 1) and June 19M (Vol. 17, Ha 2) am svafcjjle as we go to press. Some issues are reprinted without cover. The cost 81AO per imne ($1.00 each when more than three issues are ordered) from Volumes 7 thmbgh 18. From 1940 to 1948 AIHA Quarterly appeared as a section in Industrial Medicine and fhupty, however these issues of these sections have hem reprinted and am available as a unit. The complete reprint, Vela. 1-7, coats tlQJQO to members, and 88000 to cqapaniea or departments of government. Handsomely bound, complete arts of Vole. 1-18 with cumulative index are available for S2S0j0P per set. Address all orders to: George D. Clayton, Executive 8ecre.'ary, AIHA, 1412S 1*1Croat, Detroit 27, Michigan. (Back iaanes of AIHA Journal, 1958 to present, may l obtained directly from our publisher. The Williams k Wilkins Company, 428 E. Preston, Baltimore 2, Maryland, at 8IA0 eaeh brae.) - ,.