Document 6RL3oN9gr6JVyXXjMep558yR1

130 . Annals New York Academy of Sciences 48. Dugois, I1., P. Amdlard, B. De Bionicourt 4 J. Leorand. 1972. Acropathle polyvinylique professionncllc. Bull. See. Franc. Dermatol. Syphiligr. 79: 197. 49. Ockarot, R. E. St R. Hindin. 1973. The health hazards of plastics. J. Occupa tional Med. 15: 808. 50. Edmondson. H. A.. R. L. Peters H. H. Frankel St S. Bokowski. 1967. The curly stage of liver injury in the alcoholics. Medicine 46; 119. 51. Eurofaciiemie. 1972. Handclsblalt GmbH. DUsseldorf, West Germany. pRuatmi I. T_ 1957 ff'rfmlr'1*1 i -Gompanyi-Baltimore, Mdr- 2n4-diii T1` WilHr\~ 53. Filatova, V. S. St H. Sit. GrONSBERO. 1957. Sanitamo-gigicniieskic usloviya Iruda v proizvodslve polikhlorvinilovoi smolyl I meryi ikh ozdorovleniya. Gigiena Sanit. No. 1; 38. 54. Filatova, V. S., L. I. Balakhonova 4 E. Sit. Gronsbero. 1958. Gigieniteskaya kharukieristika proizvodstva khlorislovo vinila. Gigiena Truda Prof. Zabolcvaniya 2(1): 6. 55. Filatova, V. S., E. Sit. Gronsbero, N. A. Smirnova, E. A. Stulova 4 I.'V. Oresckevic. 1965. Voprosyi gigienyl truda I sostoyanie zdorov'ya rabolikh, zanyatyikh na proizvodslve laleksnovo polivinilkhlorida. Gigiena Truda Prof. Zabolcvaniya 9: 9. 56. Filatova, V. S. St V. A. Antonyuziienko. 1971. Giglcniieskiye usloviya truda i professional'naya zabolevacmosi' raboiikh proizvodstva suspenzionnovo poli vninilkhlorida v dinamike za ryad let. Gigiena Truda Prof. Zabolcvaniya 15(4): 57. Fisciier, 1., It. MuHDsetteNK 4 R. Wolf. 1965. Mllzszlntiaraphle mil 1-Bromomercuri (,,,Hg)-2-hydro*ypropan (BMHP). Foruchr. Oebiele Roenlgenstrahlen Nuklcarmed. 30Jj 349. 58. Fischer, J.. R. Wolf 4 H. GaMm. 1973. Die Milzszintigraphic. Dlsch. Arztcbl. , No. 7:401. _ '05 /" 1 au`"C .1 1 <1 A<1 Tnmnri nt [ hfj ||UA r fn . 1MaS| j nf |||| T|lll f 11 111(T,' TIT rf^Al!ir-3r^r4bippll..ETt Company. Philadatphia, Pj. 60. Gitsios, C. T. 1971. Aero-osteolysis iu PVC workers. Med. Bull. Stand. Oil Co. 31(1): 49. 61. GtiNtriER, O. 1956. Die KunsIstofTe und ilire arbeitsmedizinische Bedcutung. Zcnlr. Arbeiismcd. 6: 156. 62. Harris, D. K. 1953. Health problems in the manufacture and use of plastics. Uril. i. Ind. Med. 10; 255. 6). Harris, D. K. 4 W. Q. F. Adams. 1967. Acro-ostcolysis occurring in men engaged in the polymerization of vinyl chloride. Brit. Med. 3. 3; 712. 64. Hensciiler, D., Ed. 1972/1973. Gesundheitsschkdliche ArbeiLsstoiTe- Toxikolo- gisch-arbeilsmcdizinischc Bcgrtlndungen von MAK-Werien (Maximnle Arbelis- plniz-Konzenlralionen). Verlag Chemie. Weinhcim. West Germany. -2 65. Herri.e, K. 1962. Polyvinylchlorid. In Utlmanns Encyklopadie der technischen Chemie. W. Foerst, Ed. 3rd edit. Vol. 14. Urban 4 Schwarzenberg. Miinchen, West Germany. ---- 66. llekvtEux 4 Tessier. 1959. Qualifies observations d'exposition et d'inlollrance aux dlrivfs vinyllques et aux rfsines fiihoxyliques. Aren. Maladies Proless. 30: 61. 67. Iocs, F. I-. 1970. Portal hypertension in the presence of normal liver morphology. . Ann. N.Y. Acad. Sci. 176(1): 11 J. 68 International Labour Office. 1971. Encyclopaedia of Occupational Health and Safely. Geneva, Switzerland. Vol. 1: 387. 69. International Labour Office. 1972. Encyclopaedia of Occupational Health and Safety, Geneva, Switzerland. Vol. II: 1467. /L-r^.70. hujH, HrO. 1067 iiilngenalril hydrocarbons; 1. AHphadr-A-Iduatial Hygiene -arxHPoZlCSTUk/. V'oli lliTas.is.Megy,- D.--Wi FaaaaSt 4 D. D, Irish, frirr- 71. J avnr, N. B. 1970. Clinical and experimental aspects of sulphobromophthalcin and related compounds. In Progress in Liver Disease. H. Popper 4 F. SchafTncr, Eds. Vol. ill. G.-u.-j 4 Stratton. New York, N.Y. 7J. Judah, J. D,, A. E. K. McLean St E. K. McLean. 1970. Biochemical mechanisms of iiver irjurv, Am. J. Med. 49t 609. 73. iutte. S. 4 C. 2. Lange. 1972. Sklerodcrmieartige Hautverandcrungcn, RaynaudSyndrom end A.Vcosieolysen bef Arbeilcrn der PVC-herslelienden Industrie. Deui- Ned. '.v'cci-.r-hr. 97t 1922. VOOXZGfZ 8i9OHa Marsleiler el at.: Splenomegalic Liver Disease 131 - 74. Kelly, R. E. 1973. Vinyl chloride and acroosteolysis. J. Occupational Med. 15: 75. Kl8aJt8s. kin, G. 1969. Toxic and drug induced hepatitis. In Diseases of the Liver. L. Schi/T, Ed. 3rd edit. J. B. Lippincott Company. Philadelphia, Pa. 76. Klinge, O. 4 H. W. Altmann. 1971. Morphologic loxischer Hepatosen. MUncb. Med. Wochschr. 113: 1529. 77. Kluoe, T., H. Sommersciiild 4 A. Flatwark. 1970. Sinusoidal portal hyperten 78. Krsaiomne.rS, uCr.geGry. 468J; .2E94. .Mutchler. 1972. The correlation of clinical and environ mental measurements for workers exposed to vinyl chloride. Am. Ind. Hyg. 79. LaAnscseo,c.CJ..-E3.3, ; S1.9.JOiie, G. Stein 4 G. Veltman. 1974. Die sogenannte Vinylchlorid-Krankheil--eine berufsbedingte Systemsklerose? Intern. Arch. Arbeits- mcd. 32: i. 80. Leake, C. D. 1934. The role of pharmacology in the development of ideal anes thesia. J. Am. Mcd. Assoc. 102: 1. $ oo --AVast-GermatiyT 82. LtFivRE, M. J. 1972. Internationales Symposion der Wcrksarzic der Chcmischcn Industrie, 27-29 April 1972, Ludwigshafen. As cited in Stein el a!., 1973. 83. Leiiaiann, K. 0. St F. Fluky, Eds. 1938. Toxikologie und Hvpimi- H<- uchni- schcn Losungsmillel. Julius Springer. Berlin, Germany M ____ H 84. Lester, D.. L. A. Greenderg 4 W. R. Aoams. 1963.. W pealed exposures of humans and rats to vinyl chloride, rr ind reisoc. 3. 24i 265. 85. Lin6d4n: e8r42, .H. 1973. Laparoscopy in alcohol-induced liver 'j = 0 rology 86. MacSween. R. N. M.. J. M. Vetters, S. K. Ross. J. stone 4 A. T. Sandison. 1973. Haemangio-cndoihell Johnliver. 1. Pathol. 109r 39 88. Maltoni, C., M. Cresfi 4 P. J. R. Burch, Eds. 1973. 11 l on Cancer Detection and Prevention, Bologna, April Medica 1m. Congr. Scr. No. 275. 89. Marin, A., J. Strauss, R. Miciiiels, J. P. Benoit, R. Bai Acro-ostbolyse'd'origine professionncllc (Travail prfseti conlre le Rliumaiismc, sbance du 18 janvicr 1967). Rev. 90. Markowitz, S. S., C. J. McDonalo, W. Fethiere 4 M. cupaiionaj acroosteolysis. Arch. Dermatol. 106: 219. 91. Marsteller, H. J., W. K. Leloacii. R. MOller, S. JOii H 03 osium :erpta 1967. icaise . Oc- t f. O. l,u riroeitern 92. Mastromatteo, E., A. M. Fisher. H. Ciiristte 4 H. DaN2joer.<39; halation toxicity of vinyl chloride to laboratory animals/Am. IruT J. 5: 394; Dull. Hyg. 36: 244. =-- ......... . lM. 94. McCord, C. P. 1970. A new occupational disease is born. J. Occupational Med. 12: 234. 95. Mikkelsen, W. P., H. A. Edmondson, R. L. Peters, A. G. Redeker 4 T. B. Reynolds. 1965. Extra- and imrahcpatic portal hypertension without cirrhosis (hcpaloporial sclerosis). Ann. Surg. 162; 602. 96 Misgeld, V.. H. 1. Stolfmann 4 S. Schulte. 1973. Zur Intoxikalion durch Vinylchlorid-Polymcrisate und/oder dcren BeglciistoiTc. Z. Haul Gcschlechlskr. 48: 425. 97 Morris, J. S., T. Htut St A. E. Read. 1972. Scleroderma and portal hypertension. Ann. Rheumatic Diseases 31: 3 16. 98. Nettlesiiif, A. 4 W. J. Fink. 1961. Neoplasms of the liver following injection of tlioroirasl. Am. i. Clin. Palliol. 35; 422. 99. Oettel, II. 1963. Gewcrbcioxikologic und Physiologic cinzelner Polymcrisaie. I'olymcrisaic chlorierier Ailiylcne. In Ullniunns Encyklopadie der lechnischen to 5 O u> o\ u> o00 i "O 'oJO Zo -H R --i ,m o o m --i c: f/> m O a; X CO Sn >< o <z. > c r"1 "U Xj -< 70 Ci X--( s c a imt) Acute Inhalation Toxicity of Vinyl Chloride to Laboratory Animals E. MASTROMATTEO, M.D., A. M. FISHER, Ph.D., H. CHRISTIE, B.Sc., and H. DANZIGER, M.D. Divition of Industrial Hygiene, Ontario Department of Health, Toronto, Ontario; Department of Phytiological Hygiene, School of Hygiene, Vnivereity of Toronto, Toronto, Ontario; and Welland County General Hospital, Welland, Ontario Introduction scribed as very slight. Elimination from the body was very rapid. These authors quoted the work FIRST prepared in 1833, vinyl chloride has of Schaumann* with experimental animals. Mice, come into increased use in the last decade in rats and dogs were able to endure repeated nar the production of polyvinyl chloride resins. Thecosis without any pathological evidence of liver fire and explosion hasard of the monomer and its or, kidney damage. According to Scluiumann, narcotio properties on acute exposure are well concentrations of seven to ten per cent in air known. As an industrial material, however, it lias would lie narcotic to humans in a short time and been regarded as of moderate toxicity. A Thresh 12 per cent would be dangerous. old limit Value of 500 ppm was established by Vinyl chloride hus been studied as a possible the American Conference of Governmental In anesthetic agent. Oster and associates* noted that dustrial Hygienists. incoordinated muscular activity of the extremi No industrial fatalities associated with its use ties and cardiac arrythmias of a serious nature have previously been reported. It was therefore were observed in all six dogs used in their experi of special interest when two fatalities occurred in ment. Carr and others7 found that vinyl chloride a plant handling vinyl chloride. This plant is en produced sensitisation of the myocardium in gaged in the polymerisation of the gaseous mono three of seven dogs in which it was administered mer with the aid of catalysts. One worker died as an anesthetic agent. while cleaning out a polymerisation vessel mid the Two cases of vinyl chloride gassing occurred in other while working in a pit. Details of these two a factory in Great Britain where polyvinyl chlor fatalities have been reported by one of the au ide resin was being made, These were reported by thors.1 the Chief Inspector of Factories.1 In one case a Published information on the acute toxicity of process worker was standing outside a polymeri vinyl chloride to experimental animals proved sation vessel and washing it witli a water stream. scanty. Patty, Yant and W&ito* in 1930 reported After ten minutes of this he suddenly colli|>*c<l on the acute response of guinea pigs to vinyl across the open manhole. Artificial resuscitation chloride. They found that exposure to 20 to 40 was successfully applied. Subsequent symptoms per cent in air killed guinea pigs in a short time; experienced by this worker were tightness of the exposure to ten per cent was endured for several chest, nausea, abdominal pain and headache. The hours. Congestion and edema of the lungs with second cose occurred in a maintenance worker hyperemia of the liver and kidneys were noted. who was overcome while repairing a vinyl chloride Peoples and Leake* found the minimal anes leak. Both men were hospitalised. Another worker thetic range of vinyl chloride in mice exposed for whose hunds were accidentally sprayed with ten minutes was 8 to 32 per cent in air; 26 to 30 vinyl chloride liquid under pressure developed a per cent was fatal in ten minutes. Dogs and rab bits were anesthetised within one minute when ex|K)eed to u concentration of alxiut 18 |>cr cent in air. Recovery was very rapid with no apparent burn. This latter cose was reported by Harris.* Such burns may occur with other highly volatile material* when sprayed onto the hands as a liquid untoward effect even after prolonged anesthesia. under pressure. Lehmann ami Flury4 noted that vinyl chloride Filatova ami Gronslterg1* in 1057 re|)ortcd on was highly narcotic but luul a wide margin lw- hygienic conditions in a polyvinyl processing tween its narcotic and lethal concentrations. Its plant in thu U.S.S.K. The plunt was engaged in local irritating effect and its toxicity were de the )Hilymcrixutiou of vinyl chloride liy means of m ZQQTZGIZ Industrial Hygiene Journal 895 a catalyst. Air sampling was done and the con centration of vinyl chloride was found to vary from about 20 ppm to about 315 ppm. (U.S.S.R. Threshold Limit Value: 1 nig/Hter or about 400 ppm). A spastic tyi>e blood vessel disorder was described in workers from this plant. Because of thu recent fatalities mentioned above 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 sjiociu* of laboratory unimul. Experimental Materials ond Procedures \ Vinyl Cldoride: The vinyl chloride was supplied in a metal cylinder underpressure. A commercial grade with the following specifications was used: Specific gravity at 0*C Water content Boiling raoge *C Hydrogen chloride content Acetylene Acetaldehyde Iron Purity (per cent) Impuritiec (per cent) 0.M3-4.M8 None -- 11 to --S.S Nom 10 ppm maximum SO ppm maximum Ftttnrially iron free 00.S maximum 0.S maximum Pure vinyl chloride is a colorless gas at room temperature; its boiling point is -13.9C. It has a sweetish odor. Its flash point is given at -78C and its explosivo limits in air from 4 to 22 per cent. It has the molecular formula CHj:CHCI. Animals: Mice, rats and guinea pigs 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 same wuy. All were of the namo stage of development. ktjuipm&U: Thu inhalation chamber capacity wus 56.6 liters. It was equipped with a viewing window aud an inlet tube. Vinyl chloride was re leased in gaseous form through an adjustable valve on the top of the containing cylinder, then through connecting rubber tubing and a recali brated Fisher flow-moter. Fresh air was pumped by motor ut an adjustable controlled rate through a meter. The streams of air and vinyl chloride were combined ut appropriate rates of flow by a gloss Y-tubc loading through further rubber tub ing to the iiniinal rhainlmr inlet, to deliver a continuing stream ill the desired proportions. Calculations aud adjustments were made to pro duce thu following flow cuncuntrutions 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. No determina tions of vinyl chloride concentrations were done in the test chamber during the experiments. Experimental Procedures: Different groups of five miec, five rats and 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. 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 pigs wus ex|K>sod to a concentration of 40 Iter cent vinyl chloride in air. In all 05 experimen tal luiimuls 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 rats which were killed by exsanguination. 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 cases. The brain, adrenal, spleen, trachea, lymph nodes, and the eye were removed from represen tative animals in each group for study. The tismies were preserved in formalin and sections made for staining with hematoxyHn-eosin. Special stains were made where indicated. Observations Control Animal*: No symptoms were exliibited by the 16 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: Exposure Time (minute*} 1 ft 10 1ft 90 9ft 90 RropooK Blight irritation In n|n ud rmta Ineraeaed motor activity first la mice, than rata and guinea pigs. Incroaaad motor activity ia all rrtrin; twitching of oxtmuiliss ia mica. Pronounced motor, umtoady gait muscular incoordination In all irmlf liioo and retain aide position; muaoular incoordination, trainers and twitching of extremities in guinea piga. Mioe nd rate unconscious, guinea pigs very unaUwrly but elill atanding. Mice aud ru In deep nareoaiai guinea piga in aideposition with tramors--os* imoonactou*. Ex)>osure wus stopped und the animals removed to fresh air. AH recovered within five minutes. Twenty Per Cent Vinyl Cldoride: The response 396 October, 1960 of animals exposed to this concentration is re* corded below in summary form: Ei|Mure Time (minulca) 1 t I JO |g 20 SI 20 R**p.m*r Immetlwle irritation in mice and rU. MueouW iacoordinalion in mice and rata. Mice and raU an tlteir aiU willt marked tremora and twitching of the exlrainiliea; unateadineaa and muacuUr inco ordination in mint* iigs. Mioa and ntU imoonacioua with rapid irregular breathing, guinea irijta unmnacioua but allowing marked twitch ing. AllanimnU in W|> naroMaia; Mt|iirtH>n irregular and rapid Deep narcuaia; breathing alow and lutllow. Breathing omumhJ iu one mouae; frothing at mouth and nuatrib in mice and ntla. All aaimab in deep narauaia. Exposure was stopped and the animals removed to fresh air. Mice and ruts recovered faster than the guinea pigs and appeared normal within five minutes except for one mouse which was dead. The guinea pigs continued to show muscular in coordination, unsteadiness on their feet until 20 minutes after removal from exposure. Thirty Per Cent Vinyl Chloride: The rcsjjonse of animals exposed to this concentration is recorded below in summary form: Exposure Time (minute*) Reaponie llioe abowed irritation immediately and tha rata allowed irritation quickly thereafter. MuacuUr incoordination in mice and T/tBLg 1 Nuiulmr of Death* iu Different (Jroujw of Five Mice, Hals ami (inittea Fig* KxjMwcti for Thirty Minnie* to Varying Concentration* of Vinyl Chloride in Air Vinyl iiilnrirtc concrniration (nef cent by volume in air) laboratory animal Mice RaU Guinea pixa IU 2U W ---- 4-0---- Total 0/S 0/6 i/a 0/S l/ S/S -- .............. --------- e/i* S/IS C/6 0/6 /* 3/6* -- --. 3/20 0/16 1/16 11/16 2/# 14/60 * A delayed death occurred within 24 bourn following expoaurt. Forty Per Cent Vinyl Chloride: Only five guinea pigs were exposed to this concentration. Signs of irritation were immediately apixuvnt. Muscular incoordination uppeured within seconds. After five minutes all the guinea pigs were unconscious with slow shallow breathing. At the end of the ex|>o8ure period one guinea pig was dead auti the remaining four were in deep narcosis. These sur vivors took 30 minutes to return to their normal apiK'uruucc and 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 varying concentrations of vinyl chloride in air is shown in Table I. Pathological Findings 2 Mice and rata In aide |>oeition with marked tremora and twitehing of the eatreiuitiee; iiitieeiiUr incoordination in guinea piga with developing peralylii of tie estreiiiitiee. < All animeb unconacioue; rapid irregular reepimiiona in mioe and rata with frothing about ooae and moutii; twitching of extremitiee aliU occurred oocaaionaliy in guinea piga. 10 Reapirationa topped in mice; breathing alow and ahallow in rata: guinea piga till aahibited oceaakwai twitehing movemenu of the axtreimtiee. 11 Breathing alopped in rata: reapirmUoru alow and ahallow in guinea piga; twitehing of evtreinltiea atiil preoant In guinea piga. 10 Mioa and rata atiil; guinea piga in deep nareoeia with alow ahallow breathing Exposure was stopped and tlw animals removed to fresh air. The mice and rata were death Tltc guinea pip took 25 minutes to return to their normal appearance and activity. One guiucu pig from this group died within 24 hours following exposure. Gros* pathological and histological studies were curried out. The findings are summarised Imlow. Control Animals: These animals showed no gross or microscopic evidence of damage. Ten Per Cent Vinyl Chloride: All test unimuis survived this exposure. They wore sacrificed two weeks inter. On gross examination there was evi dence in mice of slight hyperemia of the lungs. This wus less murkod in ruts. Guinea pigs showed no difference from control unimuis. On histologic examination the mice showed very slight engorge ment of the pulmonary vessels. One mouse showed degenerative changes in the tubular epi thelium of the kidnoy with hydropic swelling. The rats showed slight congestion of the capillar ies in the lung. Luugs in the guinea pig were also slightly more hypcrumic than those of the control animals. Twenty Per Cent Vinyl Chloride: One mouse died us a result of 30 miimtcs exposure to this concentration. Pulmonary congestion was evident on gross examination. Microscopically, there was Industrial Hygiene Journal ,397 engorgement of the blood vessels in the lung with patchy amis of atelectasis and minimal edema. The kidneys showed minimal degenerative changes iu the epithelium of the convoluted tu bulin. The test animals surviving this exposure were sacrificed iu two weeks. On gross examination, congestion of the lungs wus present in all species, but it was more marked in the mice and rats than in the guinea pigs. Histologically, there was evi dence of pulmonary congestion in exposed ani mals. Some fatty infiltration wus prexent in the liver of one rat. All other tissue* studied itp|>eurnl normal. Thirty Per Cent Vinyl Chloride: Gross examina tion of the animals which died as a result of this cx|>oHurc revealed congestion of the lungs with hemorrhagic arcus. The mice and rats in addition showed congestion of the liver and kidney. The one guinea pig dcuth wus delayed. In this animal there was marked congestion of tiio lungs with hemorrhages and the liver was distended and 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 lungs. The trachea of one rat showed superficial desquamation of the epithelium. Con gestion was also evident in the liver and kidney of the mice und rats. The liver of the guinea pig which hud the delayed death showed severe fatty degeneration of the liver confirmed with frozen sections stained with Sudan III. The four surviving guinea pigs weru sacrificed two weeks later. Marked pulmonary congestion wits present with hemorrhagic areas and edema. In one cose there was evidence of secondary bac terial infiltration. The liver in these guinea pigs gave the up|)cumncc of fatty infiltration hut uo fat was demonstrated on frozen section. Forty Per Cent Vinyl Chloride: One of five guinea pigs c\|>oscd to this concentration died during the exposure and another died within 24 hours. The two which died showed marked con gestion of tlw lungs with hemorrhages on gross examination. This was also evident on micro scopic examination. Tho liver of one of these gave the appcumnco of fatty infiltration, but no fat could be demonstrated on frozen section. Tho three surviving guinea pigs were sacrificed two weeks later. Marked congestion of the lungs with hemorrhage was evident on both the gross and microscopic examination. In one guinea pig, tlie truehcul epithelium was completely absent. 1'uthoiogicul studies which weru inude of the bruin, heart, spleen, adrenals, lymph nodes and the eyes showed no difference between controls and unimuis dying us a result of exposure or be tween controls und the surviving animals sacri ficed two weeks after exposure. There was a tendency for the blood to remain unclotted in the unimuis dying during exposure. Tills feature was noted in the two human fatalities mentioned ear lier hut it is not u specific cliar&ctcristic of vinyl chloride. Discussion The nis|xmso of guinea pigs to inhalation of vinyl chloride wus similar to that reported by Putty, Yunt und Waite. The guinea pigs in our Mltirly, however, tolerated a greater oxfKMurt! dur ing the ex|*Tiirieiitul |x'ri<xl than either the miee or rat*. The results in mice ogrued closely with those rc|X)rtod by Peoples and Leake. Rats were similar to mice in their response. The pathological changes in animals which dicxl us a result of exposure were mainly those of vascular engorgement of the lungs with hemor rhages und edema. The severity of these changes vuriod with the severity of exposure. In the higher concentrations, pulmonary change was marked with severe damage to the tracheal epithelium. Congestion of the liver and kidneys also occurred in test animals. These changes are similar to those reported by Patty and assoc iates. Evidence of pulmonary congestion was still present in surviving animals sacrificed two weeks after exposure. Patty and associates reported that such changes hod disappeared in about eight days Degenerative changes in tho tubular epithelium of the kidney were noted in one mouse dying as a result of exposure and in one mouse sacrificed two weeks after being exposed. Such changes, however, were minimal and not shown by other animate iu the group. One of the guinea pigs with delayed death fol lowing ex|Mwurc showed severe fatty infiltration of the liver. Chungcs suggestive of futty infiltra tion were observed in other exposed animate but not confirmed by frozen sections stained with Sudan ill. Summary Separate groups of laboratory animate com prising five mice, five rats and five guinea pigs were exposed in an inhalation chamber to concen trations of 10,20 and 30 per cent vinyl chloride in air for 30 minutes. An additional five guinea pigs were exposed to a 40 per cent concentration for a similur period of time. The response by each of the three species to these concentrations is noted. Inhalation of these relatively high concentra tions produced narcosis and death. Mice were the most susceptible with guinea pigs considerably more resistant. Rats were similar to mice in their BFG36382 898 October, i960 response. Exposure to ten per cent vinyl chloride in air produced deep narcosis in mice and rats but no deaths; 30 per cent concentrations killed mice and rats. Exposure of guinea pigs to 20 per cent produced deep narcosis; but three of five guinea pigs survived exj>oeurc to 40 per cent con centration. Animals dying as a result of exposure were autopsied shortly after death. Survivors ami con trol animals were sacrificed two weeks luter. Gross pathological and microscopic studies were done and these findings are 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 three guinea pigs which died following exposure showed severe fatty infiltration of the liver. Survivore sacrificed two weeks after exposure showed little difference from the control uniniuls. Pulmonary congestion was still evident but liver and kidney congestion wus not. References I. PiNUdiEK, il.; AoaiduuUl J'uiroiuin by Vinyl Chlorals; Rport of Two Cue*, Canadian Urd. Auoc. J. 86: 820 (April 1900). 3. Patty, F. A., W. P. Yant, amd C. 1'. Waitw: Acuts RssponM of Guiuw Pica to V|<ora of Soma New Commercial Organic Compound# V. Vinyl Cltioride, Pnb. Ilaaltk Btpi. if: 1963 (August 1930). 3. Pboflus, A. 8., and 0. D. I.sakn: The Anaatlwtle Action of Vinyl Cltluritla, J. I'kurmuvulw fir ill (1933). 4. Lrmuann, K. B, 4 F. Fluky: Taticalofg and ilggitn* oj Mulnal MimIi, Translated by E. King and H. F. Smith, Jr., Williama 4 Wilkins, Baltunore (1943). f. &.-HAVWAMK, 0. \Cited by Lebmano, K. B. and F. Ffury. I. OaTKK, R. H., C. J. Cabs, J. C. Khamtx, amp If. J. 8aubm- wald: AumiIwsu XXVII. Nsrcoais wiUt Vinyl Chtorub, AnrtUarialotw t: 369 (1947). 7. Cake, J., R. M. Buikiimon. J. F. Vitciia, ano J. C Kkanti Ja.: Anaatbesia XXIV. Chemical Constitution of Hydro carbons aod Cardiac Autoinatidty, J. Pkarm. and A'rprr. flerap. 97: 1 (1949). 8. AmwkI Rtpart at (As Chit/ Jnepeeler / t'actoriu far lit Year iUi, London : H.M.S.O. Cmd. 8778 (March 1963). 8. Hamate, D. K.: Health I'tcbltmi in tba Manufacture and * UceofPhaUcc,Br>l.J./tid.Md. 10:386(1963). 18. Filatova, U. 8 , ano E. 8. GmoNsasso: Hygienic Working Conditions in Polyvinyl Chloride Tar PlanU. Qiyitna pp. 36-48 (January 1967). Abstracted in AM. ! World Utd. M; 89 (July 1967). Back Issues or AIHA Quarterly FOR 18 YEARS THE AIHA QUARTERLY was the publication of AIHA, then in 1958 it was changed to be the 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 hand vary from a low of 8 upward. All issues except March 1946 (Vol. 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 euch when more than three issues arc ordered) from Volumes 7 through 18. From 1940 to 1946 AIHA Quarterly appeared as a section in Industrial Medicine and Surgery, however these issues of these sections have been reprinted and are available as a unit. The complete reprint, Vols. 1-7, costs $10.00 to members, and $50.00 to companies or departments of government. Handsomely bound, complete sets of Vols. 1-18 with cumulative index are available for $250.00 per set. Address all orders to: George D. Clayton, Executive Secretary, AIHA, 14125 Prevost, Detroit 27, Michigan. (Back issues of AIHA Journal, 1958 to present, may be obtained directly from our publisher, The Williams & Wilkins Company, 428 E. Preston, Baltimore 2, Maryland, at $1.50 each issue.) fOOXZGVZ t Aeute and Sub-acute Toxicity Studies of Thallium Compounds WILLIAM L. DOWNS, M.S., JAMES K. SCOTT, M.D., LUVILLE T. STEADMAN, Pli.D., aii.l ELLIOTT A. MAYNAIID, I'h.D. Department of Radiation Biology, University of Rochester, School of Medicine and Dentistry, Rochester, New York Introduction The thallous acetate was prepared as an aque ous solution at concentrations of 1, 2 or 5 per THE element thallium wus discovered by cent. The thallic oxide was suspended (5%) in Crookes in 1801 by spectroscopic techniques distilled water containing 0.8 per cent carboxy und isolated chemically one year later by A.mcthylcelluloso. Lamy. There are no Urge industrial uses for Young adult, female and male albino rats, thallium und its production has been limited. originally of the Wistar strain (1923) and bred in The principal uses of thallium have been related the Project Colony were used. The rabbits were to its rodenticidul properties and it was formerly young, mature albinos obtained from local breed used us u depilating agent. Tiudlium salts arc ers. Guiucu pigs were young mature animals of also lim'd in the production of certain typos of optical glass und in the manufacture of scintilla tion counters. An examination of the literature reveals a number of published reports and reviews1- * * of thallium toxicity following ingestion of rodenticides containing thallium compounds, A con mixed sex und obtained from local breeders. The dogs were bcagle-type mongrels obtained from local sources. Single doses of thallous acetate and thallic oxide were administered by intravenous injection to rabbits, by intrapcritoncal injection to rabbits, guinea pigs and rats, and orally to rabbits, guinea siderable amount of work has been reported on pigs, rats and dogs. Groups of 2 to 5 rats received the depilating action of thallium compounds on laboratory unimuls und man.4, * *7 The dis tribution und excretion of isotopic thallium single oral or intrapcritoncal doses of the oom|Mmnds. Generally only one rabbit, guinea pig or dog was treated at each dose level. The LDM (Tl,#4) has been reported by u number of inves values, their confidence limits, and the slope tigators.1' * Recently, Stavinoha and co-work ers11 have demonstrated that certain compounds containing sulfur uct us protective agents against acute tiudlium im'isoning in mice. function of the regression line, were calculated by the method of Litchfield and Wilcoxon.tt AU unimals were held for a 14-day period of observa tion following injection. Tiie work rc|>rted l>elow is concerned with the acute toxicity of tlmllous acetate (TA) and thallic oxide (TO) following the administration of these compounds to several species of animals by sev eral routes. The ingestion toxicity of these com pounds was also investigated for periods up to three months. The ingestion studies were conducted using weanling (50-80 gin) albino rats. TTie basal diet was Purina Fox Chow Meal. The rats were kept in basket-typo cages aud were permitted to take food and water ad lib. The experimental diets were prepared by the admixture of the thallium compounds to the basal diet using an electric Experimental Methods and Materials mixer. Uody weights and clinical data were re corded. The two thallium compounds studied were ob At termination of the ingestion study all of tained from the American Smelting und Refining the surviving rats were sacrificed by decapitation. Co., Denver, Colorado (tludiic oxide) and Chem The nits were examined grossly and the heart, ical Commerce, Newark, New Jersey (thallous liver, kidneys, lungs, spleen, testes and femurs acetate). The purity of these compounds was were removed and their weights recorded. Sec relatively high (99.A-99.8% Tl). tions of the liver, kidney, brain, lung, spleen, This ||wr is bused on work performed under contrast with llte United SUU* Atomic Energy Commission si the University of Rochester Atomic Enemy Projeot, Rochester, New York. heart, stomach, testis, skin, and adrenals were fixed in Uouins and stained with hematoxylin and eosin for histological study. Portions of the 399