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HAND DISEASE SUMMARY This is a status report for the physicians of those plants of The B.F.Goodrich Company, where cases of "hand disease" among polyvinyl chloride manufacturing per sonnel have occurred. This information should be regarded as confidential and le not to be disseminated or discussed except to B.F.Goodrich Management personnel. CLINICAL CASES The basic characteristics of this disease have been described in an article by Wilson, McCormick, Creech and Tatum in the August 21, 1967 JAMA, a copy of which is attached. The major portion of the cases that have occurred exhibit osteolysis of the distal phalanges of the fingers and Raynaud's symptoms. We have observed a few cases with acroosteolysis and asymptomatic, and some with symptoms but without acroosteolysis. A few cases have shown suggestive lytic changes In other bones of the body. Currently, the best method of determining the presence of the disease is by x-ray. The B.F.Goodrich Company has been performing hand x-rays on all polyvinyl chloride personnel every six months. The recognition of early acroosteolysis from the x-ray requires the use of proper technique in producing the film, and expertise by the roentgenologist making the interpretation. Any Raynaud's symptoms that occur among polyvinyl chloride manufacturing personnel should be regarded as suspicious. Cases have been seen progressing from Raynaud's symptoms into marked acroosteolysis. B.F.Goodrich Company Positive and questionable cases exist at three B.F.G. plants: Avon Lake, Louis ville and Niagara Falls. Some of the cases at these plants are asymptomatic and not too definite. At three plants - Calvert City, Henry and Welland the single cases reported are questionable. Including all positive and questionable cases, the totals are: Avon Lake Louisville Niagara Falls Calvert City Henry Weiland 18 23 5 1 1 1 Acroosteolysis exists In one of the B.F.Goodrich's foreign affiliates. Other Companies Acroosteolysis has occurred in other polyvinyl chloride manufacturing companies in the United States and Europe. We believe that up to twelve other companies in the United States and Canada are involved, and at least three in Europe. EPIDEMIOLOGICAL AND RESEARCH STUDIES In the Fall of 1966 the B.F.Goodrich Company advised the U.S.A. and Canadian polyvinyl chloride producing companies holding membership within the Manufacturing Chemists' Association of the "hand problem". As a result, a research grant was made 20264002 BFG02744 2 to the School of Public Health at the University of Michigan by M.C.A. to conduct an epidemiological study. Nineteen companies agreed to participate by making hand x-rays and completing detailed work histories of their manufacturing personnel. This study Is in the final stages of completion. The results should indicate the Incidence of the disease in the Industry, and perhaps Its possible causes. The B*F.Goodrich Company has been pursuing the cause of the disease through its own research efforts. It has employed the services of the Kettering Laboratory, Cincinnati, Ohio, for both clinical studies and animal experimentation. Recently, this laboratory has reported that It has reproduced the disease in hamsters. The B.F.Goodrich Company has sponsored research at the Brooklyn Polytechnic Institute on the effects of various chemicals on collagen tissue. These studies have not yielded any information as to the cause of the disease. ETIOLOGY The cause of acroosteolysis remains unknown. It probably is related to a chemical insult arising out of polyvinyl chloride polymerisation. Any of the mono* mers or intermediate compounds produced could be the cause. In addition to the chemical Insult, probably a physical Insult and a personal idiosyncracy are necessary for the occurrence of the disease. Because of the low Incidence of the disease even among polycleaners performing the same type of work and using the same chemicals, it is probable that the personal factor plays a very definite part. Individuals should not be used as polycleaners who have abnormal responses to temperature stress. The cold Insult hand test Introduced into our plants about a year ago, should be done prior to the assignment of any individual to polycleaning. When the reports of hand x-rays are received by the plant physician from the Akron B.F.G. Medical Center, it is his responsibility to evaluate the case, discuss it with the affected employee, and decide on the necessity of reporting it to the proper state health authorities. However, no reporting to the state should be done without prior consultation with The B.F.Goodrlch Company Medical Director, mj 6/24/68 cc: Mr. John Nelson Mr. J.W. Miller, Jr Rex H. Wilson, M.D 20264003 1 T "T" BFG02745 American Industrial Hygiene Association Journal 541 were measured in (he morning and again late in the afternoon exposure periods. Table I experimental Human Exposure to Vinyl Chloride Subjective and neurological responses were measured before the subject entered the CluBlxr Concentration chamber, 15 minutes after entrance, and at (PPO*) l-hour intervals (hereafter. Flannagan Co X S.D. ordination and Crawford Manual Dexterity 59 261 2 8 J I Tests were conducted at inidmoming and 493 491 again in the afternoon. Breath sampling be 7 3 lUnjc <PPn) 65- 33 m-243 318-471 523-473 TWA* (ppm) 48 248 4 4918 Kuoibcr { Subject* 6 4 4 7 gan immediately after the subject left the `Tiw-wijht*d averafe ceoccsintiM based on 7S (wan indtidJnf a OJ-hour lunch period ia an uaconunlnaied exposure chamber. A 24-hour postexposure arcs. urine sample was collected and a blood sam Kiaaiiatnui upofura for S.9 hours. ple was drawn the following morning for r SGPT, LDH, alkaline phosphatase, BUN, Table 1 shows the analyzed concentration creatinine, apd bilirubin determinations. to which the subjects were exposed. Calcu Analysis of Breath Data lations of the mean and standard deviation of exposure concentration are based on chart The decay curves for the breath vinyl chlo readings from the infrared spectrophotometer l ride concentrations were constructed by step taken at 5-minute intervals over the two 3.5wise multiple regression using a digital com hour exposure periods. The TWA is based puter. An empirical relationship of the form on the total 7.5 hours which included a 0.5- Concentration -- f (TWA, time) was select hour lunch period in an uncontaminated ed from a choice of several terms, each based area. on TWA and/or time. The resulting regres sion equation best represents the ordered re lationship between breath vinyl chloride con centration, time-weighted average exposures, The final breath decay curves intended for use as an index to VCl exposures were ad justed to TWA concentrations of 50, 250, and {>ostcx|)osurc time. Each breath decay curve has an associated standard error of regression which can be used to compute the confidence band for any chosen-level of significance. The 95Cc con fidence band for the mean of a group of ob servations was chosen in this case to describe the statistical error associated with the breath data and the regression technique. I Results Experimental Breath Curves A total of 13 men participated in the three experimental chamber exposures at nominal concentrations of 50, 230, and 500 ppm pro ducing a total" of 160 valid breath data points. Five of the six subjects exposed to 50 ppm were re-exposed at 500 ppm 2 days later. There was no measurable residual vinyl chloride detected on the breaths of the sub jects prior to the second exposure. Serial breath sampling was initiated immediately after the subjects left die exposure chamber and continued up to 20 hours following the exposures. Ficure 5. Breath decay curves based on experi- nv.-tital exposures to 50, 'J50. :nu! 500 ppm .(' Vtll <?T*-!)C>uf TWA). V. :r } * *. -'< *-iaJT. Uw- ' i >; *>. . ;*'s* :( j i! :< i! ill iiS 'J v * i i} > ill ! -m I .*if ti hi .< J Ml- : , J l!ti ill! m !I O 4* CO o o Cfl ; ;.if BFG02593 I0 *I I . I- li 542 Novetnber-Decetnbrr, IDGfJ A HU I < DAILY VARIATION IN EXPOSURE TO VCL VAPOR (8 hr. TWA) with confidence bands only slii;|iily wider titan those from controlled human experi ments. The close similarity between these curves and those constructed from controlled exposure data arc further illustrated in Fig ure 8. Human Responses t* n n u n 0oy* ol tf Monis aivrr sm> a Figurk 6. Variation in VC1 vapor exposure for three shifts. and 500 ppm (Figure 5). A lOO-ppm decay carve was interpolated from the available data using regression analysis. These curves arc presented with the calculated 95% con fidence bands for the mean of a group of ob servations. On-the-job Breath Curves Ten workmen participated in the on-thejob breath sampling program, producing a total of 91 usable sets of data. Ten percent of the breath samples collected were discard ed because of pipet leakage or poor sampling techniques. Absolute breath levels ranged from about a 20 ppm in one sample taken less than 1 hour after an 8-hour TWA of 250 ppm, to barely delectable levels (<0.05 ppm) in samples taken after exposures at TWA's below 50 ppm. The extremely broad variation in the TWA's cx]>cricnccd by workmen during one of the periods in which breath sampling wasbeing conducted is demonstrated for three shifts of men bearing the job classification "coagulator operator" (Figure 6). Minute, hourly, and daily fluctuations in the concen tration of a contaminant are most descriptive ly revealed by continuous monitoring. This method of sampling quickly points out the fallacy of judging TWA and peak exposure concentrations on the basis of spot sampling or periodic surveys of brief duration. The remarkable correlation between breath concentration and corresponding TWA valttes made it possible to construct the series of breath decay curves shown in Figure 7, Front a subjective standpoint no significant untoward affects were noted at any of the cxjjostirc concentrations. The only complaints were those of two subjects who rci>oried mild headache and some dryness of their eyes and nose during the 500-ppm exposure experi ments. No odor was detected by anyone entering the ex[>osurc chamber at 50 ppm. At 250 ppin all four subjects entering the chamber initially reported that they could detect a very slight odor of the chemical. Five of the seven subjects entering the exposure cham ber at 500 ppm were able to detect the odor of VCI, but after 5 minutes of exposure those five were unable to detect it even with forced inspiration. Three of the four subjects re entering the chamber after lunch were able o N> 1-V;i'ki: 7. CO oottreath decay curves derived from O)rcaih data eullcclcd from workers foUowinp rn- ic-job exposures to VCI vapor (8-hour TWA). to dvl could for ap the cm TIl' neuroh nifiram ordinal cd din: lalxu.u CX|X*sm cantU - .DlSCUSS: The survey inant. . late tieone i> tration incnts * on a conduc. yxis of compiv: valid l'i CXpOMIt On ti constru ing com agreeinchamlxshould od for .- The ods sbcirCum-: sired. 1 ing pc.sv tinuous trends a: identify equipiur. sources lems 111*: vironnn-r by rcdiu net. C-onii: tretneiy i ment ret; ffir r-i'-j vV4v-i--bJ>" "'-- A BfG02594 , 1969 wider xperi- thosc trolled i Ffc- 'ficant i f the taints mild and i\|vri- I UTitur t 230 utthcr *vt a i the hamodor those .... ed r>h American Industrial Hygiene Association Journal to detect a faint odor of VCl. One subject could detect a faint odor on deep inspiration for approximately In minutes after entering the exposure chamber. The exposure had no noticeable efTect on neurological responses, nor did it produce sig nificant changes in the results of mental, co ordination, or manual dexterity tests conduct ed during the exposure jxniod. All clinical laboratory ` studies performed in the poseexposure period were normal and not signifi cantly difl'erent front pre-exposure values. Discussion The object- of the environmental health survey is to identify the atmospheric contam inant. determine the exposure level, and re late this to the health hazard it presents. If one is to judge hazard by ambient concen tration measurements, then those measure ments must accurately describe the exposure on a continuing individual basis. A carefully conducted survey combining continuous anal ysis of the work room atmosphere with a comprehensive job study will provide data valid for estimating time-weighted average exposure," On the other hand, breath decay curves constructed from breath data collected dur ing continuous plant monitoring are in close agreement with those obtained from exposure chamber experiments with-VCl. These curves should therefore be useful as a second meth od for assessing exjzosurc to VCl vapor. The choice of whether one or both meth ods should be used depends on prevailing circumstances and on the thoroughness de sired. For example, data useful in describ ing peak cxjxjsurcs are obtained from con tinuous monitoring. Concurrently, exposure trends and concentration gradients tuny lie!/) identify plant operational inefficiencies and equipment malfunctions by revealing specific sources ol omission. Clot reeling these prob lems not onlv restores a healthful work en vironment but often results in bonus savings Iiv redueine losses of raw material and prod uct. Continuous monitoring, however, is ex- tivmrlv to'th both t:i tiuu- and itt the equip ment lequiud. The M<ijie of data acquired is Figure 8. Comparison of breath decay curves derived from the on-the-job data and the experi mental human exposure data. limited by the number of sampling probes, and these probes are not always capable of accurately measuring the individual's daily exposure experiences, especially should these involve unusual incidences such as chemical spills or exposures outside the monitored area. Breath analysis has the advantage of in dividualizing each worker's integrated daily exposure. Bread) decay curves, as an index of exposure, offer a means of estimating the average daily individual exposure on the basis of a few breath samples taken serially in the [jostexposure period. Consequently breath analysis can be vised to diagnose as well as quantitate an exposure which has already occurred. It is a relatively inexpensive and simple method which can be put into opera tion without extensive and costly preliminary preparations. However, postesposure breath analysis docs not provide information on the daily iluctuations of exposure, and the peak exposure con centrations ate not made e\ idem by hieatit data. Kmallv bieath .uuiWms is not auuhi.i- ?. i "5 ro : \LJL\lLMj]j^ M*i\\\ i | f| . r .1 a ,v* y.V.'v i' ? Xu*'.* .- -S'-'t "V,."H--<vyVyysy tiy.xt.'.HVv-prf /. "V'!yT.'n,."Tj,-,` l5* 1 b b V.-K.ha-.W-- :.s -. : " BFG02595 544 November-December, /Od'.l ble to all chemicals, and breath decay curves established for one chemical arc not useful as an index of exposure to any other chem ical. The decay curves presented here arc in tended to serve as an index of exposure to vinyl chloride vapor and arc based on an exposure duration of 7,5 hours for the experi mental exposures, and 8 hours for the on-thejob study. The close agreement between the two sets of curves and the narrow confidence bands obtained in each case demonstrate the usefulness and accuracy of both methods for estimating TWA exposures and indicate the importance of breath analysis and the need for expanding its use in evaluating ex posures to other widely used volatile organic chemicals. References l. I'r.trmos. J. K., II. K. |(ov '. and E. J. Scil\nu: Tl.e Application nl (oAifimrr Science to In.lunrial ||v. ioif. A Imii, tlyg. Ana I-. 77; lao-ias (Maicl. 19**). 2. Srr.WABT. R. I).. 11. II. (J*v. 1). S. F.M.r.v. C. L Mak* and A. W. Scii.rua: Human Kvi>mure Tetrad.1UM,I Fih><cn Vapor: KetacionUiip n( I'.xpiccd Air and ()(,,( Oinmniradont n anti Tnxirity, Arrh Knrtmn Health 2: 5lft-52'2 (May I'Kil). 3. Snwtar R. D., II. II. Cav. O. S. Eatjrr, C. L. I(*n,. and j. F.. I'CTTA.aon: OWrviiinni on tl.r Conrentralimi of Trkhlnencdiylri.e in III.mhI and Expired Air lollnw- in F.xpouire o( ffumani. A**rr. lad. list- Anar. I V? 1A7-I70 (April 1%'J). 4. Stt.ivabt. K. U.. and V. K. Kovvc: Quinre AndT.tudcn wr le 1,1 .UTrichlomethane. Arrh. Matadi'< Pro/rti. 29: I9I-201 (1967). 5. R. D., If. C. pm"., F.. I). IWarTTA. ami A. \V, SciiArrui: ll.iina.i KsiH-ure tn Styrene Vapor. Arrh. Environ, Health 16: No. S {May l!X>fl|. 6. Ste\va*t. R. J).. E. D. Bahctta. f{, C. Doon. mJ T. R. Twkmaon: Experimental Human Exposure to Tetrachloroethylene. AM.i Arrh. Environ. Health. (In print). 7. Stwaat, R- D.. It. C. Dow. E. D. IUhfita, A. w SenArm, and J. E. MUTCittra: Ct.rn.iie OvcreypnMi.r to Bemene Vapor. Presented at die Srtth Annual Meet ing of the Society of Tuxicologv. March 23-23. 19M. Atlanta. Georgia. Received May 26. |!HJt Notices and Deadlines It is the policy of the AiHA Journal to accept and publish notices and short items of import and interest to our readers subject to the limitations of available space. This is done as a service to our profession and no fee is charged for such announcements. Some notices are received too late to be carried to advantage in our Jour nal. Persons supplying announcements to us should keep in mind the time schedule of our publication. The Journal appears six times per year with the copies being mailed about the 20th of February, April, June, August. October, and December. While emergency or urgent notices can be inserted up to three or four weeks before the mailing dale, such cannot he assured. Normally the announcements should be in the Editors hands at least two months or more before tlic issue in which they should appear. Perhaps these guidelines will aid you announcement generators. 20243008 T BFG02596 fndu Acute Inhalation Toxicity of Vinyl Chloride to Laboratory Animals E. MASTROMATTEO, M.D., A. M. FISHER, Ph.D., H. CHRISTIE, B.Sc., ant! H. DANZIGER, M.D. Division of Industrial Hygiene, 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 scribed as very slight. Elimination from the br:y was very rapid. These authors quoted the wnA FIctRhoemSeTprionpdtroeupcinaticroernedaosifnedp1ou8lsy3ev3i,innyvtlihnceyhllloacrsihdt leodreircdeaesdinehsa.insTheoraf tSs cahnadumdoagnsn5wweriethaebxlepetorimeenndtuarleanreimpeanlste. dMn: -r- cosis without any pathological evidence of Uv.: fire and explosion hazard of the monomer and its or kidney damage. According to Scliautieiar.. narcotic properties on acute exposure arc well concentrations of seven to ten [H'r cent in l:: known. As an industrial material, however, it has would l)e narcotic to humans in a short time an : been regarded as of moderate toxicity. A Thresh 12 per cent woultl lx* dangerous. old Limit Value of 500 ppm was established by the American Conference of Governmental In Vinyl chloride has liectt studied as a pvfd*v dustrial Hygienists. anesthetic agent. Oster and associates* noted l:* incoordiuutcd muscular activity of the cxtnn::- Xo industrial fatalities associated with its use ties ami cardiac arrythmias of a serious natur- have previously I icon rejwrted. It was therefore were observed in all six dogs used in their oxp'ri- of s|M`ei:il interest when two fatalities occurred in iiieiit. Carr and others7 f<umd that vinyl rlilor;-!-- a plant handling vinyl chloride. This plant is en produced sensitization of the myocardium a. gaged in the ]ioiymcrizatiuu of the gaseous mono three of seven dogs in which it was ndtiiitiUtcn't mer with the aid of catalysts. One worker died as an anesthetic. agent. while cleaning out a polymerization vessel and the Two eases of vinyl chloride gassing occurred i:. other while working in a pit. Details of these two a factory in Great Britain where |Hily vinyl ch!**r- fatalities have ls-en reported by one of the au idu rosin was Ix-ing made, These were rcjMirted!;. thors.1 tin* Chief lns|Ks*.tor of Factories.'1 Ill one cas- Published information on the acute toxicity of process worker was stamliug outside a jxilyuu-r:- vinyl ehloride to exjiermiental animals proved zation vessel and washing it with a water do shinty. Fatty, Yant ami Waite5 in 11)30 re|Kuted After ten minus's of this he suddenly collai*-' on the acute n*s|xmse of guinea pigs to vinyl across the o|wn manhole. Artilieial resuscits.: ' chloride. They found that ex|ostiro to 20 to 40 was successfully applied. Subsequent sympt- r - per cent in air killed guinea pigs in a short time; experienced by this worker were tightness o: *: exposure to ten ]x*r cent was endured for sevei-al chest, nausea, alxtominal paiu and headache. : hours. Congestion and edema of the lungs with second ease occurred in a maintenance w.-r-- hyiHjremin of the liver and kidneys were noted. wln was overcome while repairing a vinyl chi*'".* Peoples and l>,akeJ found the mimiiial anes leak. I tit 11 men were hospitalized. Anot her "or-.*' thetic range of vinyl chloride in mien exposed fur whose hands were aerident-nllv sprayed ten minutes was S to 12 per eent m air; 2a to 30 vinyl chloride liquid under pressure develop-*1 |j*r cent was fatal in ten minutes. I )ugs and rab bits were anesthetized within one inmule when bill'll. This latter ease was reported be lkn";- exposed to a concent rat ion of alxnif IS per rent Sued hums may oceur with other highly ve:*' in air. Herovery uas very rapid with no apparent materials wlien sprayed onto the hands :iJ a h';'* untoward I'll'eeL even after prolonged anesthesia. under pressure. D'hiuann and Flniv* noted (hat vimyl eldoniIc Filatova and (boiisU rg"1 in re|Krlc>; was highly narcotic liti(. had a wide margin 1k*- Ingienie conditions in a |xlyvinvl prod'***" - tu'irn it< rianiitii- am! lethal eom i 111 ra t n ms. tls plant, in the t'.S.S.U. 'Hie plant Was eng:'-` local inhaling < IV<< l. and its toxieity wen* de the polymerization of vinyl ehloridt: In in"..... I a cat i i cervtr I from i Tlire ]l|)U\ descr I lie f abov i tion 1 ciall; for i i infoi cal c f anin i Expr V ill a t S|. iI w*.. tty! .V.si A***-' 1 n*ii `;rr 1:u|* i ten an* **et> m' fro -I U;i w: w: foO to ** o o i BFG02597 .'limln'nl ll'/gitnc Journal yst. Air s.'t111pitttir vvjiji dune :ml (h<* rou.nlniliou of vinyl cMmiili' w.-is found lo vary - in :ilmill, 20 ppm lo :iluul. -I I fi |>|>11). (If .S.S.ll. lm>lioN| Limit. Viilur: I ing/litrr or nlioiit MX) jiin). A spastic type Iilnoi[ vr,<.'[ tlisnrtler was turns of vinyl chloride roiieeut.ruliou.K were done m the test rlminlicr during the ex|>ci'iiiienU<. 1'lsiH`riiitrnlol /'roenhircjf: I )i(TeiiMit groups of live mice, five rats and live guinea pigs were placed in (.he chandler and excised for thirty x'rilM'd in workers from this plant. Horim.xr of flic ......... falalil.ir* mentioned hove it wns derided lo undertake acute inlialaoii studies in laUiialory animals with roinmorally available viuyl chloride. This wns done UHh minwte.x Mi einireiitratinTis of 10, 20 anil 30 per cent, vinyl rlilmiili- in air. Similar groups of mil* tro] animals were maintained hut noL e.\|K>sod to vinyl eliloridc. At (lie end of thirty minutes cxjwisure the U`st animals wen; imimsliately re nr comparison with curlier work nod to provide ^formation on the* acute response awl patholngi| changes in morn than one sjieeir* of lulionitory ,nim:d. moved t<> fresh air. An additional group of five guinea pigs was cxjxiscd to a concentration of 40 per cent vinyl chloride in air. In all 05 cx(>criim:ittnl animals were involved. Oljscrvatinus were rc- conled on the animals during and after cjqxuuirc. 'iperimental Materials and Procedures The animals which died either during the cx- posure or after a delay jicriod were autopsied soon Vinyl Chloride: The vinyl chloride was supplied after death. Two weeks after the exposure sur * a metal cylinder under pressure. A commercial viving test animals and controls were sacrificed ill, :ur ;nilc with the following si>ccific:itioiis was used: gravity at 20*C 0.9*3-0.f> by a blow to the head with the exception of four control rate which were killed by exsanguination. All animals were examined for gross pathologi liirr eonlrnt None tdin* mnee *C -II to --0.5 cal changes. Tissues were removed from all ani ;.lwn eliloride content None mals for microscopic examination. The lungs, 'Hvlrno -rtiMchydo jitv {per cent) -puritiw (ptfr cent) 10 ppm rrmximum 30 lie"1 maximum Essentially iron free 90.5 maximum 0.5 maximum 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 tissues were preserved in formalin and sections made for Pure vinyl ehlorklo is a colorless gas at room staining with hcmatoxylin-cosin. Special stains A :n|>eraturc; its Ixiilmg point is -- i3.9C. It has were made where indicated. vwetish odor. Its Hash point is given at -- 7SC <1 its explosive limits in air from l to 22 |>cr at. It has the molecular formula OII-tCHCl. \tiim/ilx: Mice, rats and guinea pigs were used .the study. Tost ami control animals were taken ai the same lalioratory stock. Ail were fed a `.mlard commercial diet and housed in the same -,r. All were of the same stage of development. Observations Control A nimah: No symptoms were exhibited by the 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: &{\iipmcnl: The inhalation ehaudx*r capacity s 56.G liters. It was cquip|>ed with a viewing Exposure Time (minute*) Response .ailow and an inlet tube. Vinyl chloride was re- Slight irritation in mice and rate. ed in gaseous form through an adjusUvl.de .ivc on the top of the containing cylinder, then ugh connecting ruhlx-r tubing and a recalijtivl Fisher flow-meter. Fresh air was pumped Increased motor activity first in mice, then nit* and guinea pip* Increased motor activity in ail specie*: tw-itchine of extremities in mice. Pronounced tremor, unsteady gait and ; motor at an adjustable controlled rate through r,utor. The streams of air ami vinyl chloride recombined at. appropriate rates of flow by a . -i Y-tul>c leading through further rubier tub- muscular incoordination in all specie*. Mice and alt in aide position; muscular incoordination, tremors and twitehinfi of extremities in guinea pie*. 23 Mice and rata uncouaeiotis, ffuinen pigs ; t<> the. animal chandler inlet, to deliver a .tinning stream in the -desired prn[xrtions, filiations and adjustments were made to pro< the following flow concentrations of vinyl very unsteady but still standing. Mice and mu in deep narcosis; guinea pigs inside position with tremors--one unconscious. ride in air for delivery: 10, 20, 30 and 40 ]>er Exposure was stopped and the animals removed All concentrations are expressed in this re- to fresh air. All recovered within five minutes. n.vs per cent by volume in air. No determina- Twenty Per Cent Vinyl Cldoride: The response 20244002 BFG02598 TT S96 October, /.v Imhtsl of animals exposed to this concentration is re corded below in summary form: Exposure Time (minute*) I 3 10 IS *0 25 30 Response Immediate irritation in mice and rata. Mitsculur incoordination in mice and mta. Mice and rut* on tlieirsidca witli marked tremors und twitching o( the extremi ties; unsteadiness &n<l muscular ineoordinntion in juinen pics. Mice and rata unconscious with rapid irrcjcuUr breathing; guinea pigs' unconacioua but showing marked twitch ing. All animal* in deep narcosis; respirations irregular and rapid. Deep narcosis; breathing slow and sliatlow. rcathing ceased in one mouse; frothing at mouth and nost'ilsin mice and rats. All animats in deep narcosis. 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 res|>onse of animals export'd to this concentration is recorded Ix'low in summary form: K|-isurc Time (inimiU'O Response Mice sIhiwciI irritation iiuiiiediandy and tlic nil* liuuvl irritiition quickly tlicmifti'r. 1 Muxciilnr incuordimtlion in mice und ruts. 2 Mire und rats in nido (ONition with murkisl tnuiiorn uihI twitching nf Out <-xtri-iniiH'n; muscular incoordination in giiim-H pigs with duvdopin* pnmly- sis o( tlic oxin-iiiitius. 5 All ntiiiimls uncorucioua; mpit] irn-gulur rcapimtions ill mice und ruts with frothing ulioui nose mid mouth; twitching ol cMremitias still occurred occasionally in guinea pics. 10 Tlr.spi ruliori'. n1ii|i| n-d in nm*s; hrruthing .slow iuil mIiuIUiw in mis; guim-i pigs nlill rlliilii In 1 ornciiiniil (Wltl-lillii; iiwivi*i*k`kIh <tin* r\Iivmitiv-. IS Itii'Hihi'ig -- 'it in min; r. *n|.i I ill inri.n hlmr rin.l . li 'i 11< in* pi g 11 i iii'H piicx; tsvil**l,ni< nl i'\t ri'ini I irn -litl pri-nrlit in kiii ln-:i puii'. dll Mir........nl l.l I - .'><11; gniui u |'i-> ill ilil'p run,-in nil). nl.i 'I,nil'... I.i.uIliii.g Exposure was stopped .-tint (In- a nil in Is remove* 1 to fresh air. Tin* liner and rats were dead. The guinea pigs look 2a niiimles (n rvliun (u their normal appearance anil arlivily. < )m- guinea pig from (his group died m i! I in i 2 1 limits fallowing e.\p< isiiiv. ITable Number of Deaths in Different Groups of Kn Mice, Rata and Guinea Pigs Exposed for Thirty Minutes to Varying Concentrations of Viml Chloride in Air Vinyl chloride concentration {per cent by volume in air) Laboratory animal Mice Rais Guiru-a TuUl 10 20 30 40 Total 0/8 I/S S/8 -- 8/lS 0/5 0/5 5/5 -- 5/15 C/s 0/5 I/S* 2/5* 3/20 0/15 /U 11/15 2/S it/yt * A delayed death occurred within2-t hours following ripen*. Forty Per Cent Vinyl Chloride: Only five guim-s pigs were cxijosod to this concentration. Signs V. irritation were immediately apparent. Muscular incoordination apiK'uml within seconds. Aft--r five minutes all the guinea pigs were imeonscii'U* with slow shallow breathing. At flic end of tl:<e.\|sisim> |mtnmI one guinea pig w as dead and d.r remaining four were in deep nareosis. These sur vivors took d() minutes to return to their normal npiK'anuu e and uetivity, but one diet! within i!w following 21 hours. The muiilier of deaths oeeurring in tlifTervist groups of five lalmratorv animals cN|xscil f<*r thirty ininutes to varying concentrations of vinyi chloride in air is shown in Table i. Pathological Findings Gross pathological and histological studies wen* carried out. Tlic findings are summarized Ixrluw. Control Animate: These animals showed gross or microscopic evidence of ilamage. Ten Per Cent Vinyl Chloride: All test auim;i!survived this exposure. They were sacrificed t" weeks later. On gross examination there was -vi(lenee in mice of slight hyperemia of the Tliis was less marked in rats, (iuim-a pigs >lno1- ' no tlilVeiviir-e from control animals. ()n liislnl"cxammal inn t i ic m u-e sin >\ved verv slight cue": !:> nienl. nf the puhnnnniy vessels, One inei:-showed degenerative changes in 1 lie t ill'iilar e| r 1 helium of the kidney with hydropic nwHei: 1 lie I'ats showed slight, congestion nl |hr raj1!.hr ies in I lie lung. 1 .tings in I he gui nea pig .-re ;i:slightly more iivpetrinie I halt I hose ui the i nn!!'" animals. 'i'tniihi l`ir Crnl l ini/1 ('1,/iniilt One tnoii-died as a rexili. nf :;p minute.-. r\|>o>mv n> if- eniH-elil I'a I H HI. I 'llhunn.'UW I < *1 igest In 11 w a - >1 !*`;;' mi gl'n.-s e\a ti unit t ic 111. M n-1\ isenpiea 11 c. t here w ;* t .-pgnrg | |i;dclv i The I i rltangi ( hales. ; The ( iacrilif ('linger j \cut it in the i deuce | mals. I liver I tmim. | T/ tinll ( expoIsi-nw ,-iuiw one then henn j Jriah ( whie \ jmln ring sug gest' of t! whi* deg. ! see, i1 ! tWn war In ten ; g;^ I tat :; > git In u g 'T' T BFG02599 00930DH9 20244004 h.s/nol .U/7 ,,l-rn..-lll id 11"' v ll>'- 1l">^ "i<h .ir,.;|S uf :> in I mimmiil clrm:i, 'kidiicvs .-l'""'i'd mmiimit i ;i t ive jn i),r n,>ll..'imm m' llu- i on vc dutr. I I ii- H. t*sl uniinub surviving this < \p<>-.ni* nri.in 1"" 'veek*. On u.n>~> < \;i i in mil n m, uf (he l'ins;s wms |>ivn.iiI. in :ill Np.vies, :il it 'v:is nn>ri m:irk',il in tin1 nnrr :nn I mis Ilian . |ln [iiiinra pigs. 1 lisl<ili>gn\'itl v. then- wns cvi- of pnlinmiMiy mtigestinn in exposed ani- :,|s. Some fall'' infill ral ion was present in flu: ,t of one rat. .Ml other ( is.-ues si n<Inal Mppenrvd anal. Thirty I'cr Cent 1 in'/I Chl"> iilc: Gross rxamina:i of the animals whieh died as a result, of this Vimsiire revealed congestion of the Jungs witli innrrhngic areas. The mice a ml rals in adilit ion .Owed congestion of the liver ami kidney. The -H'guinea pig dealli was delayed. In this animal `in' was marked congest mu of the lungs with iiierrhages and the liver was distended and verv -.,1'le. 'Hie unei'oseopie elianges in the animals lii.h died inelmled marked engorgement of the ilmonarv blood vessels with eilema and liemoi-ages in the hlllgs. rile t rachea of one rat. showed .,;r/icial desquamation of the epithelium. (`on* ; -tii>n was also evident in the liver and kidney :tlr mien and nits. 'Hie liver of the guinea pig had the delayed death shower! severe fatty ;.-:rnenition of the liver confirmed with frozen : ..lions stained with Sudan III. Tlie four surviving guinea pigs were sacrificed fo weeks later. Marked pulmonary eongi*stion i* present with hemorrhagie areas and edema. ihh: ease there was evidenre of secondary bae rkil infiltration. The liver in tln'sc guinea pigs aiv tlie appearance of fatty infiltration hut no .t iv;is demonstrated on frozen section. YmUj Per Cc.nl Vinyl Chlnriilr: One of five ainea pigs e.\|x>sod to this concentration died ;ring the rxjx>siire and another died within 24 iirs. Tlie two whieh died showcrl marked eon* .'tion of the lungs with hemorrhages on gross `emulation. This was also evident on micro pir examination. The liver of one of these gave appearance of fatty infiltmtion, but no fat uM be demonstrated on frozen section. The three surviving guinea pigs were sacrificed 'i> ivi'eks later. .Marked congestion of the lungs ;:li hemorrhage was evident on both the gross -) microscopic examination. In one guinea pig, tracheal epithelium w:is completely nl>scnt. I'atliological studies whieh' were made of the , "dnr heart, spleen, adrenals, lymph nodes and * **ycs showed no difference between controls I animals dying as a result of exposure or be'.fn controls and the surviving animals 3acri- fio'il fun weeks jiftcr exposure. There was a I I'lidi'iu'v fur I hr blond to rrinaiu imi'lollrd in the :mim.-ds dying during iwjiosniv, This fratnre Mas nnl i'i I in 1.| ir t.wi > human fa (a lit irs m<nl ioned ear lier 1ml. it is not a specific characteristic nf vinyl rlil< n il Ir. Discussion Tlir response of guinea pigs to inhalation of vinyl eltloride was similur to that rc[H>rlcd by Patty, Vaiit. and Waite. 'Hie guinea pigs in our study, however, tolerated a greater exposure dur ing the exiHu imental jx'riod than either tlie mire or rats. Tlie results in mice agreed closely with those reputed by Peoples and Ix;ikc. Rats were similar to mier in their res|>onsp. The pathological changes in animals whieh died as a resulL of ex|X)sure were mainly those of vascular engorgement, of the lungs with hemor rhages and edema. The severity of thi'se changes varied with the severity of ex(Hisinv. In the higher eoneentralioiis. pulmonary ehange was ntarkid with severe damage |o the tracliml epithelium. ('ongestion of lln` liver and kidneys also occurred in test uuimuls. These changes nn* similar to those n')M>rted by Patty and associates. Kvidence of pulmonary eongestion was still present in surviving animals sacrificed two wt*eks after exposure. Patty ami axsoriutes reported that such changes had disapjx'anal in about eight days l)<*gencnitivn changes in the tubular epithelium of tlie kidney were noted in one mouse dying as a result of ex|x>surc and in one mouse sacrificed two weeks after Ix'ing rxjx)f?nl. Such changes, however, were minimal and not shown by other animals in the group. One of the guinea pigs with delayed death fol- . lowing exposure showed severe fatty infiltration of the liver. Changes suggestive of fatty infiltra tion were observed in other exjjoscd animals but not confirmed by frozen sections stained with Sudan IH. Summery Separate groups of laboratory animals 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 n similar period of time. The response by each of the three R]x:cics 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 ! 398 October, SC'.. 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 exposure to 40 j>cr cent con centration. Animals dying as a result of exposure were nutopsied shortly after death. Survivors and con trol animals were sacrificed two weeks later. Gross pathological and microscopic studies were done and these findings arc dcscrilxxl. The principal pathological changes in animals dying from exposure were congestion of the lungs with pulmonary edema ami 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. Survivors sacrificed two weeks after cx)>osure showed little difference from the control animals. Pulmonary congestion was still evident but liver and kidney congestion was not. References 1. D&MStoem, H.: Accidental PoUonia* by Vinyl ChluriJ*. T-. port of Two Cuw, Canadian hied, Ammoe. J. St: f'S tW0). 3. Pattt, F. A., W. P, Yaht, akb C. P. Waits: Acute of Guinea Pit* to Vapon of Some New Coniinnriil Oic.xj Compound* V. Vinyl Chloride, Pub. Health Itcpt. \ti (Aucujt 1030). 3. IVenn, A. 8., and C. O. Lbakc: Thu Anctdietic Anise.! Vinyl Chloride, J. Pharmacology (8: 231 (1933). 4. Lkiiuakk, K. B., it Y. Flukt: Fur/eefotiyend //jiVw. Indutlrial Selventi. Translated by E. Kitt* and H. F. Jr., William* it Wilkin*, Baltimore (1913). 6. SciiAtncAHM, O.: Cited by Lehmann, K. B. and F. F1un` 0. Oerut, IL II., C. J. Cam, J. C. Kbanti, anu M J. Sv.i wau>: Ancetliceia XXVII. N*reo*i* with Vinyl Chlor. ir. AnertArtaelefy t: 399 (1917). 7. Cam, J., IL M. Buhoiaox, J. F. Vitcha. and J, C. Kton Jjl: Anesthesia XXIV. Chemical Conatitulion of llvii-* Cnrboua and Cardiac Aulomaticity, J. Pkarm. and l':p~ Then?. WT: 1 (1949). 8. Annual Report of the Chief Ineprctor of Faetoriee for tU . mt, London : II.M.S.O. Cuid. 8773 (March 1933). 9. Hamm, D. K.: Health 1`rabVctn* In the Manufacture Use of I'laatica, Bril. J. /ltd. Ned. 10: 299 (1993). 10. Filatova, U. S, axu R. 8. Cbo.ni>iikuo: Hygienic Worlai* Conditions in l'olyvinyl Chtori<tc Tar 1'laat*. Gii*** f3S-12 (January 1997). Abstracted in AIM. of l' trrll $5<l. X. 69 (July 1997). Back Issues of AIHA Qvartekly p\)R IS YEARS THE A1IJA QUARTERLY wits the publication of AIHA, then JL in i`j5S 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 nil back issues of the Quarterly. For individual issues quantities on hand vary from a low of $ upward. Ail issues except March If'-Ui (Vol. 7, No. 1) and June F.WiG (Vol. 17, No. 2) are available as we go to press. Some issues are reprinted without cover. The cost is 1.50 |K*r issue (SI.0(1 each when more than dirts? issues are ordered) from Volume: 7 through IS. ' From I'-'IO to 1040 AlllA Quarterly np]ieaml as a section in Industrial Medicine and Surgerv, liosvever these issues of these sections have been reprinted and arc available as a unit. The complete reprint, Vols. 1-7, costs 10.00 to member.-?, and $)().IK) i<> companies or dcparlmciiis of government. Handsomely bound, complete si-is id' Vol-. I - I s with cumul.-ti i ve index are available for ?2f0,00 jmt set. Address all orders to: (leoige I). Clayton, Executive Secretary, AIHA, 14125 I'levost, 1 let rott. 27, Michigan. (|',.-iel< i-sii<-- of . I f /I A J minull, HloS (o |i resent, may Is* obtained directly from our publisher, The Williams A Wilkins Company, 42S K. I'reslon, Jlallimore 2, Maryland, at. SI .10 each is-uc.) 4 f i Introc Tc i i aiul LilU i (hall The } to it li<cd also i optr ( tion i A' t mm tlial ii vide 1 >idt the l:d >i 1 (rib rn- 1 \ 20244005 > BFG02601 HE NEW YORK ACADEMY G' SC i t.CLo WORKING GROUP ON ia> flU - io TOXICITY OF VINYL CHLORIDE-POLYVINYL CH........ .. "ENVIRONMENTAL CONCERNS BEYOND THE UORKELAC? 20245001 Glenn E. 5tKvii:er Director, Office of Toxic Suostanres Environmental ProtxCt'^n Agency 401 M Street. S. w Washington. j. 1. 2VIV' BFG02602 Presentation to the Working Group on Toxici ty of Vinyl Chi or i de-Pol yviny'i Chloride The New Yor* Academy of Sciences New Yi..rk City, New York May 11, 1974 "ENVIRONMENTAL CONCERNS 3EYONO THE WORKPLACE Glenn E. Schweitzer Director, Office of Toxic Substances Environmental Protection Agency Washington, D. C. During the past several months vinyl chloride nas awakened _. ; elements of the environmental community to the presence of the plastics industry. In some respects it is fortunate that we have been alerted in a rather dramatic fashion to the need for greater attention^to this important segment of our industrial base which will sorely continue to expand in the years ahead. While this symposium is directed to cne existing and potential risks involved in the manut arttirp -iv.cr uut . and use of vinyl chloride monomer (VCM) and polyvinyl cnlcr-ie many of the types of considerations and mcoi tainri* <h.*< turte these deliberations undoubtedly characterize a tar broader swathe of concerns over chemicals in general. Hopefully, we can extrapolate hon our current experiences with VCM and PVC in identifyina prociem. wnh other potentially important commercial cnemicas eariv ir. i|h>,. onic stage and thus minimize the economic dislocations aK^vjan.. ct corrective actions. Unfortunately, the proposed Toxic Substances Control Act r>a$ lodged in a Joint Committee of the Congress for ten months i* very powerful tool for addressing the vinyl chloride nroHnm. and similar problems with other chemicals, in an aaequat* manor .s noi available to the federal Government. Wo must relv nn -tnor .Ldtuuory authorities and on tne oower of persuasion n our efforts to insure that our population is not oemq unnecessarily exposed to concent 'at inns of VCM and other chemicals used in connection with VCM it particu larly distressing that until this statutory authority is o**- zr.v- . the Federal Government wii; not be equlnped - -.n t^mr, if ,, n^d personnel and .supporting resources - to wtn civ intricacies of this type of toxic Su*;V-\in,_e problem in a manner which wl insure full attention t.o the balancing of risks and benefits. Today I will report to you on tne preliminary i nves' :u.t nd~r taken by the Environmental Protection Aqencv ourino me .-a*. :.v~r: months, vie are still sever-.': weers away from rgdi.huio even tentative conclusions as to who l ao<jit`unai steps, if any, should he raken hv :ha Agency concerning VCM/^vC activities. Our monitoring data a^e not yet 20245002 BFG02603